PMID- 1913742 TI - Magnetic resonance characteristics of the LGM vena cava filter: technical note. AB - The LGM (Vena Tech) IVC filter is a recently introduced device for caval interruption. The magnetic resonance imaging safety and imaging characteristics of this filter were evaluated. The filter was proven to lack ferromagnetic properties. It was imaged with minimal artifact and no detectable motion in the magnetic field. PMID- 1913743 TI - Inadvertent embolic obstruction of abdominal aorta from left atrial thrombus after percutaneous mitral valvuloplasty. PMID- 1913744 TI - Route dependent effects of 2-chloroadenosine and theophylline in isolated perfused guinea pig hearts. AB - STUDY OBJECTIVE: The adenosine hypothesis for the metabolic regulation of coronary blood flow remains controversial, in part because of differences in results obtained between intravascular and endogenously released adenosine. The main objective of this study was to compare the responses of coronary perfusate flow to intravascular and pericardial 2-chloroadenosine and theophylline. The periocardial route was used to simulate physiological conditions. DESIGN: An isolated, perfused guinea pig heart preparation was used. Hearts were submerged in 10 ml Krebs-Ringer bicarbonate solution having the same chemical composition as that used to perfuse the coronary vasculature. The submersion fluid was assumed to simulate myocardial interstitial fluid. Hearts were divided into four experimental groups. The first group (n = 6) was used to check that the submerged hearts functioned normally. The second group (n = 12) was used to compare differences between intravascular and pericardial 2-chloroadenosine. The third group (n = 16) was used to evaluate the two routes of administration of 2 chloroadenosine on transmural distribution of coronary flow. The fourth group (n = 24) was used to test the effects of hypoxia in the absence and presence of pericardial theophylline. EXPERIMENTAL MATERIAL: Hearts were obtained from adult guinea pigs of either sex weighing 300-400 g. MEASUREMENTS AND MAIN RESULTS: All submerged hearts were functionally stable for at least 30 min. Pericardial 2 chloroadenosine was about 1000 times less potent than intravascular 2 chloroadenosine in relaxing the coronary vasculature. Venous concentrations of pericardial 2-chloroadenosine were significantly greater than those of intravascular 2-chloroadenosine, at 0.72(SEM 0.17) v 0.18(0.02) mumol.litre-1. Pericardial 2-chloroadenosine caused more uniform distribution of radiotracer microspheres than intravascular 2-chloroadenosine. Finally, pericardial theophylline significantly attentuated the vasodilator response to hypoxia but not to exogenous adenosine. CONCLUSION: The isolated submerged heart is a viable preparation for investigating the adenosine hypothesis. Our results suggest that intravascular adenosine does not simulate physiological conditions of interstitial adenosine release and action. PMID- 1913745 TI - The cellular basis of intrinsic sinus node recovery time. AB - STUDY OBJECTIVE: The aim was to investigate the mechanism of the intrinsic sinus node recovery time. DESIGN: The effect of 2 min periods of 20% and 50% overdrive on the electrical activity of fibres in the sinoatrial node was studied in isolated atria of rabbits under complete autonomic blockade (atropine 3 x 10(-6) M and propranolol 3 x 10(-7) M). EXPERIMENTAL MATERIAL: Rabbits (New Zealand white) of either sex up to 3 kg weight were used. MEASUREMENTS AND MAIN RESULTS: The first returning cycle after overdrive is prolonged not only by the time needed for retrograde plus antegrade conduction but also by a delay in impulse formation (overdrive suppression). During pacing, action potential duration, amplitude, maximum diastolic potential (only in primary pacemaker fibres), and diastolic depolarisation rate were all decreased. Action potential duration, amplitude and maximum diastolic potential returned to control value during the first cycle following a period of overdrive, but diastolic depolarisation remained depressed during many consecutive cycles. In primary pacemaker fibres, diastolic depolarisation appeared to be depressed throughout diastole. In latent pacemaker fibres diastolic depolarisation was depressed only in the second part of the diastole. CONCLUSIONS: Sinus node recovery time has two components: (1) a conduction component of both retrograde and antegrade conduction, and (2) a depression of the automaticity (= overdrive suppression), which is only due to a slowing of diastolic depolarisation. PMID- 1913746 TI - Lovastatin prevents the impairment of endothelium dependent relaxation and inhibits accumulation of cholesterol in the aorta in experimental atherosclerosis in rabbits. AB - STUDY OBJECTIVE: The aim was to determine the effect of the HMG CoA reductase inhibitor, lovastatin, on the loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta produced by feeding a diet enriched with cholesterol. DESIGN: The study was conducted in two stages. In stage 1, New Zealand white rabbits were randomised into four groups. Group 1 (n = 15) was fed standard rabbit diet for 6 weeks. Groups 2 (n = 15), 3 (n = 12), and 4 (n = 12) were fed standard rabbit diet supplemented with 2% cholesterol for 2 weeks followed by standard rabbit diet only for the next 4 weeks. In addition, lovastatin (4 mg.kg-1.d-1) was given for the entire 6 weeks in group 3 and for the first 2 weeks only in group 4. In stage 2 a second group of animals was fed a diet supplemented with 0.5% cholesterol for 2 weeks in order to match the serum cholesterol levels in groups 3 and 4 of stage 1. EXPERIMENTAL MATERIAL: Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation (to acetylcholine), contractile responses (to noradrenaline), relaxant responses (to sodium nitrite), and sudan staining. Serum was obtained for measurement of cholesterol and triglyceride concentrations. MEASUREMENTS AND MAIN RESULTS: In stage 1, at the end of 2 weeks, the serum cholesterol was significantly lower in groups 3 and 4 than in group 2. At 6 weeks, endothelium dependent relaxation to acetylcholine (-6.0 log mol.litre-1) was impaired in group 2 compared to the other groups: group 1 78.5(SEM 5.0); group 2 43.5(7.8)%; group 3 79.4(4.6)%; group 4 84.7(3.4)%. The relaxant response to sodium nitrite was not impaired in group 2. Further, the aortic tissue cholesterol concentration in group 2 was significantly greater than that in group 1, at 355(65) v 105(10) nmol.mg-1 protein. In groups 3 and 4, the aortic cholesterol concentrations were significantly lower than those in group 2, at 74(4) and 94(17) nmol.mg-1 protein respectively. In stage 2, the serum cholesterol values were matched to those in groups 3 and 4 of stage 1. In these animals, after a further 4 weeks the aortic cholesterol was significantly greater than in group 3. CONCLUSIONS: Lovastatin attenuates the accumulation of cholesterol and preserves endothelium dependent relaxation in this model of experimental atherosclerosis. It is likely that the latter is a secondary phenomenon. PMID- 1913747 TI - Noradrenaline turnover and metabolism in myocardium following aortic constriction in rats. AB - STUDY OBJECTIVE: The aim was to provide meaningful information on the function of the sympathetic system soon after an increased pressure overload on the heart. DESIGN: Noradrenaline storage, turnover, uptake, and synthesis were investigated at 3, 14, and 28 d after aortic banding in rats. Sham operated rats without aortic banding were used as control group. EXPERIMENTAL MATERIAL: Left ventricle, spleen, and kidney from male Sprague-Dawley rats (175-200 g) were used in this study. MEASUREMENTS AND MAIN RESULTS: Cardiac noradrenaline concentration was decreased at 3 d and 28 d after banding and increased at 14 d; left ventricular mass was increased from 14 d onwards. The rate of change in the specific activity of myocardial noradrenaline (noradrenaline turnover) as well as dopamine beta hydroxylase, an enzyme for noradrenaline synthesis, was unaltered at 3 d, increased at 14 d, and decreased at 28 d after aortic banding. Myocardial [3H]noradrenaline uptake, on the other hand, was decreased at all time points studied. The changes observed in the myocardium at day 14 were specific since noradrenaline turnover rate was unaltered in other peripheral organs such as spleen and kidney. Furthermore, after ganglionic blockade with pentolinium, both sham operated control and banded animals had identical, low noradrenaline turnover rate constants, and significant restoration of cardiac weight and noradrenaline stores was observed in the hearts from banded animals. CONCLUSIONS: Noradrenaline turnover and metabolism are altered soon after imposing increased workload on heart. Whether or not the changes in the sympathetic activity are a prerequisites for hypertrophy still remains to be seen. PMID- 1913748 TI - Induced ventricular arrhythmias in regionally denervated porcine heart with healed myocardial infarction. AB - STUDY OBJECTIVE: The aim was to test the hypothesis that chronic sympathetic denervation of the boundaries of a healed myocardial infarction may modify the arrhythmogenic response to programmed electrical stimulation. DESIGN: Electrical induction of ventricular arrhythmias and infarct size were evaluated in a control group of pigs with a one month old myocardial infarction induced by ligature of the left anterior descending coronary artery below the first diagonal branch. These were compared with a group of similarly infarcted pigs subjected to regional denervation of the peri-infarction area induced by topical pericoronary application of phenol. Denervation was verified by the absence of adrenergic histofluorescent reaction to glyoxylic acid in myocardial samples. EXPERIMENTAL MATERIAL: 24 pigs (weight 15-20 kg) with myocardial infarction were studied, 13 of which were subjected to regional peri-infarction denervation, and 11 acted as controls. MEASUREMENTS AND MAIN RESULTS: Programmed ventricular stimulation with one to four extrastimuli at 500 and 400 ms basic cycle length at the left and right ventricles induced fewer episodes of ventricular fibrillation in the denervated than in the non-denervated group (five episodes in three pigs v 14 in nine pigs, p less than 0.005), but more episodes of sustained ventricular tachycardia (79 in eight pigs v 23 in two, p less than 0.001). Unlike fibrillation, induction of ventricular tachycardia increased with multiple extrastimuli and with short basic cycle length. The denervated preparations tended to develop smaller infarcts but this difference was not statistically significant: infarct weight (g) relative to total ventricular mass (g) = 7.2 (SD 2.4)% v 10.5(4.5)%. CONCLUSIONS: Neural integrity of the non-ischaemic myocardium bordering a healed infarction modulates inducibility of ventricular tachycardia and fibrillation during programmed ventricular stimulation. PMID- 1913749 TI - Reduced prostaglandin release from the stunned porcine heart--significance for attenuated reactive hyperaemia. AB - STUDY OBJECTIVE: Since both reactive hyperaemia and membrane phospholipids are altered even after short lasting ischaemic periods, the release of PGE2 and PGI2 in the basal state and during early reperfusion was examined to determine whether it was changed in the stunned myocardium. The effect of prostaglandin synthesis inhibition on reactive hyperaemia was also examined. DESIGN: The distal left anterior descending coronary artery was occluded for brief periods and coronary flow was recorded by Doppler flowmetry. In subgroups: (1) a shunt was established draining the ischaemic region for determination of myocardial prostaglandin release associated with 2 min of ischaemia before and after a 10 min occlusion; (2) prostaglandin synthesis was blocked between two 2 min occlusions by infusing indomethacin into the left anterior descending artery; and (3) segment lengths were measured in the left anterior descending artery region subjected to consecutive periods of 2, 10, and 2 min of ischaemia, and in a control region. EXPERIMENTAL MATERIAL: 21 pentobarbitone sodium anaesthetised pigs, weight 21-30 kg, were used. MEASUREMENTS AND MAIN RESULTS: 30 min after the 10 min occlusion, systolic shortening was reduced by 38(18-57)% (median +95% confidence interval; p less than 0.05). Concomitantly, basal PGE2 and PGI2 release was reduced by 69(30 77)% (p less than 0.05) and 58(7-81)% (p less than 0.05), respectively. During early reperfusion after 2 min of ischaemia, PGE2 release was reduced by 53(17 86)% (p less than 0.05) after development of stunning, whereas PGI2 release remained unaltered. Blockade of prostaglandin synthesis did not affect reactive hyperaemia either in normal or in stunned myocardium. CONCLUSIONS: Prostaglandin release from the stunned myocardium is reduced. Since indomethacin did not affect reactive hyperaemia, the attenuated PGE2 release during early reperfusion in stunned myocardium cannot explain the concomitant reduction in reactive hyperaemia. PMID- 1913750 TI - Relationship between placental blood flow and combined ventricular output with gestational age in normal human fetus. AB - STUDY OBJECTIVE: The aim was to quantify the changes in placental blood flow and combined ventricular output with gestational age in normal human fetuses to determine the percentage of total cardiac output that placental blood flow represented, and whether this changed with age. DESIGN: Two dimensional echocardiographic images of the umbilical vein, the proximal aorta and proximal main pulmonary artery were obtained, and cross sectional areas calculated from vessel diameters. Doppler velocity signals were recorded from each vessel and digitised to obtain velocity-time integrals. Placental blood volume flow and combined ventricular output were calculated as the products of flow velocity time integrals and cross sectional areas of the umbilical vein, and of the great arteries respective. SUBJECTS: Subjects were 64 normal human fetuses aged between 20 and 42 weeks gestation. MEASUREMENTS AND MAIN RESULTS: Placental flow and combined ventricular output both increased exponentially with gestational age (r = 0.79, and r = 0.84; both p less than 0.001). Placental flow correlated linearly with combined ventricular output (r = 0.69; p less than 0.01) and comprised almost one third of total cardiac output throughout the second and third trimesters. CONCLUSIONS: These data describe the relationship between placental blood flow and combined ventricular output with age in the normal human fetus and provide a substrate by which placental insufficiency and resulting intrauterine growth retardation may be recognised early. PMID- 1913751 TI - Angiotensin II induced phosphorylation of myosin light chain in vascular smooth muscle cells from spontaneously hypertensive and normotensive rats. AB - STUDY OBJECTIVE: The aim was to determine the changes in the phosphorylation of myosin light chain induced by angiotensin II in cultured vascular smooth muscle cells derived from normotensive (WKY) and spontaneously hypertensive rats (SHR). DESIGN: Extracts of vascular smooth muscle cells incubated with [32P]orthophosphoric acid were subjected to 4M urea-SDS electrophoresis, followed by autoradiography and laser densitometry. EXPERIMENTAL MATERIAL: Confluent primary cultures of vascular smooth muscle cells from aorta, superior mesenteric arteries and cerebral arteries were used. MEASUREMENTS AND MAIN RESULTS: The basal myosin light chain phosphorylation of SHR did not differ significantly from that of WKY. Stimulation with 1 nM angiotensin II increased incorporation of 32P into the myosin light chain, which peaked at 4 min and then slowly declined until 15 min. Exposure to angiotensin II (0.001-10 nM) for 4 min evoked a dose dependent increase in the phosphorylation of myosin light chain with a maximal response 40-45% above basal values. No significant differences in the response to angiotensin II were detected between cells derived from the two strains. Saralasin, a specific angiotensin II antagonist, did not affect the basal phosphorylation of myosin light chain but completely abolished the effect of angiotensin II. CONCLUSIONS: Angiotensin II enhances the phosphorylation of the myosin light chain from vascular smooth muscle cells in aorta, mesenteric arteries, and cerebral arteries, but there are no differences in response between SHR and WKY. PMID- 1913752 TI - Cytosolic calcium staircase in ventricular myocytes isolated from guinea pigs and rats. AB - STUDY OBJECTIVE: The aim was to study intracellular calcium dynamics underlying positive or negative tension staircase of mammalian hearts. DESIGN: Changes in cytosolic calcium concentration [( Ca2+]i) in single ventricular myocytes were investigated using a Ca2+ indicator, fura-2. Beat to beat alterations in fura-2 fluorescence and cell edge movement on resumption of stimulation were recorded on video tape, and analysed by a computer based image processing system. EXPERIMENTAL MATERIAL: Single ventricular myocytes were enzymatically isolated from the hearts of 30 adult guinea pigs and 25 adult rats. MEASUREMENTS AND MAIN RESULTS: In guinea pig ventricular myocytes, the positive contractile staircase was associated with ascending staircases of both peak systolic and end diastolic [Ca2+]i because of a cumulative increase in diastolic [Ca2+]i. In rat ventricular myocytes, the negative contractile staircase was accompanied by a descending staircase of peak systolic [Ca2+]i, while end diastolic [Ca2+]i level was unchanged due to the rapid decay of [Ca2+]i transients. Ryanodine (10 microM) reversed the mode of [Ca2+]i and contractile staircases from negative to positive in rat myocytes, whereas it caused minimal alteration in guinea pig myocytes. CONCLUSIONS: Tension staircase of mammalian hearts depends on diastolic Ca2+ level as well as Ca2+ handling by the sarcoplasmic reticulum. The positive staircase may require progressive increase in diastolic [Ca2+]i, while the negative staircase may be mediated by depletion of activator Ca2+ in the sarcoplasmic reticulum. PMID- 1913753 TI - Local adenosine infusion and myocardial oxygen supply and consumption in reperfused canine myocardium. AB - STUDY OBJECTIVE: The aim was to determine whether a local infusion of adenosine could increase coronary blood flow to restore fully the O2 supply to consumption balance in reperfused myocardium. DESIGN: The left anterior descending coronary artery was occluded for 2 h followed by a 4 h reperfusion with and without simultaneous local infusion of adenosine (50 micrograms.kg-1.min-1). In another group, adenosine was infused for 4 h. Small artery and vein O2 saturations (microspectrophotometry) and regional flow (radioactive microspheres) were determined. SUBJECTS: 25 anaesthetised open chest mongrel dogs, divided in three groups, were used in this study. MEASUREMENT AND MAIN RESULTS: In the central group, 2 h occlusion decreased regional blood flow below normal. After 4 h of reperfusion, blood flow was less than normal in the affected area, at 57(SD39) affected v 85(31) ml.min-1.100 g-1 control. O2 extraction was higher in the reperfused area, with 61% of veins having O2 saturations less than 35%. For the experimental group, adenosine was infused into the left anterior descending artery at a dose of 50 micrograms.kg-1.min-1. Adenosine coupled with reperfusion increased regional blood flow above control in the affected area, to 267(238) ml.min-1.100 g-1, but this was less than was found with adenosine alone. O2 extraction in this area was lower than with reperfusion alone, with only 1% of veins having O2 saturations less than 35%. CONCLUSIONS: A large flow reserve is present in reperfused tissue and the low O2 saturations found in reperfused myocardium cannot be due to vessel blockage (greater than 20 microns in diameter). Thus local adenosine can be used to mobilise the reserve to improve the O2 supply to consumption balance. PMID- 1913754 TI - Electrophysiological effect of varied rate and extent of acute in vivo left ventricular load increase. AB - STUDY OBJECTIVE: The aim was to determine whether the rate, the magnitude, or both, of increased left ventricular wall stress in vivo has consistent and prominent effects on repolarisation, afterdepolarisations, or arrhythmogenicity. DESIGN: Ten anaesthetised dogs underwent transient proximal aortic occlusion. Wall stress was estimated from pressure-volume data obtained by volume catheter, normalised to preocclusion values, and correlated with simultaneously determined changes in monophasic action potential duration (MAPd). Data were obtained during both fast (greater than 50% rise in wall stress within two beats) and slow occlusions, as well as during innervated and denervated conditions. EXPERIMENTAL MATERIAL: Adult mongrel dogs (20-25 kg) were used. MEASUREMENTS AND MAIN RESULTS: Two- to threefold increases in wall stress resulted in less than 5 ms shortening in MAPd and there was little correlation between wall stress and MAPd shortening. The strongest relation between normalised wall stress (EWSnorm) and MAPd was observed under denervated conditions during rapid aortic occlusion (delta MAPd = 2.5 x EWSnorm +2.1, r2 = 0.44, p less than 0.001). Afterdepolarisations were observed in fewer than 10% of occlusions and were not related to the magnitude or rate of loading change. Ventricular ectopy occurred more frequently during rapid than slow occlusions (87% v 56%, p = 0.01), but was unrelated to the level of wall stress increase or the presence of afterdepolarisations. CONCLUSIONS: Marked acute increases in left ventricular loading in vivo minimally alter repolarisation, and rarely lead to afterdepolarisations. The speed rather than magnitude of load change appears more important in the development of ventricular ectopy. These findings suggest that load induced ventricular ectopy is due to stretch induced automaticity rather than triggered activity or re-entry. PMID- 1913755 TI - Functional and electrophysiological effects of oxidant stress on isolated ventricular muscle: a role for oscillatory calcium release from sarcoplasmic reticulum in arrhythmogenesis? AB - STUDY OBJECTIVE: The aim was to investigate the cellular basis of oxidant stress induced arrhythmias by studying the influence of oxidant stress on the contractile and electrophysiological function of isolated cardiac muscle. DESIGN: Oxidant stress was induced by the photoactivation of rose bengal added to the solution superfusing isolated ventricular muscles from a number of species. Measurements of contractile and electrophysiological function were made under control conditions, during exposure to oxidant stress, and under a number of experimental conditions. EXPERIMENTAL MATERIAL: Isolated superfused papillary muscles or trabeculae from rat, rabbit, or frog hearts were used in all studies. MEASUREMENTS AND MAIN RESULTS: The contractile response to oxidant stress was assessed by measuring isometric developed tension and resting tension throughout the experiment, and the electrophysiological response was assessed by recording action potentials using conventional 3 M KCl filled intracellular electrodes. Oxidant stress induced a transient positive inotropy, after-contractions, and eventually contracture. Associated with these contractile changes were prolongation of the action potential, early afterdepolarisations, oscillations in resting membrane potential, and automaticity. These effects were concentration and species dependent and the oscillations in both tension and membrane potential were abolished by inhibition of calcium release from the sarcoplasmic reticulum with caffeine. CONCLUSIONS: The contractile and electrophysiological effects of rose bengal induced oxidant stress are consistent with a cellular calcium overload. The observation that the oscillations in tension and membrane potential were abolished by caffeine and that these effects were species dependent (rat greater than rabbit greater than frog) suggests a role for oscillatory sarcoplasmic reticulum calcium release in these effects. The oscillations in membrane potential and the automaticity induced by rose bengal are likely to underlie the arrhythmias observed in isolated hearts exposed to oxidant stress that have previously been described. PMID- 1913756 TI - Metoprolol and ventricular repolarisation and refractoriness: lack of chronic adaptational class III effects in rabbit. AB - STUDY OBJECTIVE: The aim was to examine the right ventricular electrophysiological changes during metoprolol treatment and in conditions of stress in the adult rabbit. DESIGN: Metoprolol (6 mg.kg-1) was given twice daily for four weeks. Stress was induced by constant infusion of adrenaline (15.2 micrograms.kg-1.h-1) via osmotic pumps implanted in the left femoral vein. Control rabbits were treated with saline. Electrophysiological recordings were made weekly in conscious animals using bipolar pacing electrodes implanted in the right ventricular apex. SUBJECTS: Adult male New Zealand white rabbits, 2.8-3.3 kg, were used (n = 7 adrenaline/metoprolol treated, n = 7 adrenaline/saline treated, n = 7 saline/metoprolol treated, and n = 7 saline/saline treated). MEASUREMENTS AND MAIN RESULTS: Recordings were made of the effective refractory period and of the stimulus-T interval of the paced evoked response. Stimulus-T is used as an index of ventricular repolarisation time. No significant electrophysiological changes in these variables were observed throughout the study. CONCLUSIONS: These results indicate that chronic metoprolol therapy does not result in a class III antiarrhythmic effect in this in vivo rabbit model. PMID- 1913757 TI - Endothelium dependent vasodilatation following brief ischaemia and reperfusion in anaesthetised swine. AB - STUDY OBJECTIVE: The aim as to compare the responses of intracoronary infusions of ATP, an endothelium dependent vasodilator, with adenosine following brief ischaemia (10 min) and reperfusion in a model of myocardial stunning. DESIGN: In group 1 (n = 6), coronary blood flow and endocardial (endo) and epicardial (epi) percent segment length shortening were measured in the distribution of the left anterior descending coronary artery before and during maximal intracoronary infusions of either adenosine or ATP (20 micrograms.kg-1.min-1). Measurements were obtained before and after myocardial stunning both at control heart rate and during atrial pacing (150 beats.min-1). In group 2 (n = 6), myocardial blood flows by microspheres and arterial-venous lactate and oxygen differences were determined following the same ischaemia-reperfusion protocol to characterise transmural changes in blood flow and metabolism in this model of stunning. EXPERIMENTAL MATERIAL: The experiments were done on 12 anaesthetised swine, weight 25-39 kg. MEASUREMENTS AND MAIN RESULTS: In group 1, baseline endo and epi segment length shortening were 16(SD 3)% and 14(6)% and following reperfusion were reduced to 10(4)% and 8(6)% respectively (p less than 0.05). Prior to stunning, minimal coronary resistances during adenosine and ATP were 0.81(0.40) and 0.76(0.25) mm Hg.min.ml-1 respectively and following reperfusion were 0.86(0.31) (NS) and 0.85(0.23) (NS) mm Hg.min.ml-1 respectively. Infusion of either vasodilator enhanced function by 30% following reperfusion whereas no such effect was observed prior to ischaemia. In group 2, no maldistribution of blood flow was observed following the same ischaemia-reperfusion protocol to account for this vasodilator enhancement in function. Percent lactate extraction values were 29(11)% and 25(14)% at preischaemic control and paced heart rates respectively, and following reperfusion were lowered to 0(12)% without pacing (p less than 0.05) and -1(34)% during pacing (p less than 0.05). CONCLUSIONS: Brief ischaemia and reperfusion in swine induces myocardial stunning without altering the vasodilator responses of either ATP, an endothelium dependent vasodilator, or adenosine. Recruitment in postischaemic segment length shortening was observed during infusions of both vasodilators at a time when maldistribution of flow was not observed. Possible mechanisms include either enhanced washout of lactate from the reperfused myocardium or greater utilisation of substrates during higher blood flows. PMID- 1913758 TI - Clinical testing of thermally stimulated cardiovascular oscillations in man. AB - STUDY OBJECTIVE: The study assessed the physiological validity of an automatic thermal stimulation method to induce synchronised oscillations in the neural cardiovascular control system. DESIGN: Automatic alternating rhythmic warm and cool immersion of different skin areas of 18 males was done at different frequencies and water temperatures. The neurally mediated responses to the periodic thermal stimulation were measured from skin blood flow and heart rate and compared to those of a sham stimulation. Respiration was monitored for control purposes. The reproducibility of the stimulation and responses was examined. SUBJECTS: 18 young males volunteered for the study. MEASUREMENTS AND MAIN RESULTS: The water bath method produced reproducible thermal stimulation and responses of skin blood flow and heart rate. Rhythmic thermal stimulation at 0.013-0.096 Hz synchronised the oscillations of the forearm skin blood flow when the thermal stimulus amplitude exceeded 10 degrees C. The increase in the stimulus amplitude or enlargement of the stimulus area did not further increase the oscillatory response of skin blood flow. Sham stimulation or mean temperature of the periodic thermal stimulation in the range 23-33 degrees C did not influence the oscillations of skin blood flow. Local cooling of the stimulated lower legs attenuated the response of skin blood flow. Both thermal stimulation and sham stimulation affected heart rate, but no stable synchronisation of the periodic heart rate variability was found at supine rest. Thermal stimulation of the sitting subjects' forearm instead of legs increased the synchronisation of the periodic heart rate variability. CONCLUSIONS: The response of skin blood flow agreed with the theory of the thermal entrainment. In a supine man, both thermal stimulation and non-specific central nervous influences induced significant and reproducible interactions with periodic heart rate variability and respiration. PMID- 1913759 TI - Effect of glyceryl trinitrate on distensibility of peripheral muscular arteries in humans is not mediated by prostaglandins. AB - STUDY OBJECTIVE: Vasodilator prostaglandins have been claimed to be responsible for the coronary haemodynamic and venodilator effects of glyceryl trinitrate, although conflicting results have been reported. The aim of this study was to evaluate whether vasodilator prostaglandins play a role in the effect of glyceryl trinitrate on the distensibility of peripheral muscular arteries in healthy humans. DESIGN: A non-invasive technique, impedance plethysmography, was applied to the assessment of the effects of sublingual glyceryl trinitrate on the compliance of the forearm and digital arteries. The subjects studied received placebo (on two separate occasions), indomethacin (100 mg orally), or ibuprofen (800 mg orally) 1 h before glyceryl trinitrate (0.3 mg sublingual) on four occasions separated from each other by at least 48 h. Blood pressure and heart rate were measured by standard techniques; changes in peripheral arterial compliance were evaluated by impedance plethysmography of the forearm and finger. The study was double blind, cross over, placebo controlled, and randomised. SUBJECTS: 12 healthy male volunteers were enrolled in the study. All subjects were fasting for at least 10 h and had abstained from smoking and from methylxanthine or alcohol containing beverages. MEASUREMENTS AND MAIN RESULTS: Glyceryl trinitrate increased heart rate by 11.6(SEM 1.6) beats.min-1 (p less than 0.0005) and diastolic blood pressure by 8.7(1) mm Hg (p less than 0.01), and decreased systolic blood pressure by 8.7(1.5) mm Hg (p less than 0.01) in placebo treated volunteers; the amplitude of the plethysmograph c wave in the forearm and in the finger was also augmented, by 120(11)% and 78(13)% respectively, indicating an increase in arterial compliance. The results obtained in the two placebo sessions did not differ, indicating good reproducibility of the system. Pretreatment with either indomethacin or ibuprofen did not modify the effects of glyceryl trinitrate on heart rate, blood pressure, and arterial compliance in the forearm and the finger. Both indomethacin and ibuprofen suppressed prostaglandin synthesis, as shown by the striking inhibition of serum TxA2 concentration, by 97.2(1.5)% and 93.7(3.0)%, respectively. CONCLUSIONS: Sublingual glyceryl trinitrate, in doses used clinically, induces a reproducible increase in peripheral arterial compliance in healthy volunteers; prostaglandins do not play any significant role in this effect. PMID- 1913760 TI - Importance of basal nitric oxide synthesis in regulation of myocardial blood flow. AB - STUDY OBJECTIVE: The aim was to investigate whether basal coronary vascular tone and myocardial perfusion depend upon endothelial nitric oxide (NO) synthesis. DESIGN: Myocardial blood flow and vascular resistance of the left and right ventricles were studied before and after intravenous infusions of either NG-nitro L-arginine (L-NA), a specific inhibitor of NO synthase, or L-arginine, the precursor of NO synthesis. Radiolabelled microspheres were used to study myocardial blood flow in small tissue sections. EXPERIMENTAL MATERIAL: 14 anaesthetised male cats, weight 2.1-3.5 kg, were used. MEASUREMENTS AND MAIN RESULTS: Measurements were made before and 15 and 40 min after L-NA treatment (30 mg.kg-1 bolus followed by 1 mg.kg-1.min-1 infusion; n = 8), and before and 15 min after L-arginine treatment (30 mg.kg-1 bolus followed by 10 mg.kg-1.min-1 infusion; n = 6). L-NA significantly reduced coronary blood flow to the left and right ventricle, by 30(SEM 9) and 48(6)% respectively, after 15 min, but only to the right ventricle, by 45(8)%, after 40 min. Mean arterial pressure and myocardial vascular resistance were raised during the L-NA infusion. In contrast, L-arginine did not elicit any change in the variables studied. CONCLUSIONS: The conductance of the coronary vascular bed and the resting myocardial blood flow is regulated by L-arginine derived nitric oxide, and exogenous L-arginine availability is not a limiting factor in this NO generation. PMID- 1913761 TI - Influence of posteruptive age of enamel on its susceptibility to artificial caries. AB - Epidemiologic studies and caries experiments with animals have suggested that caries susceptibility of teeth decreases with age. Observations on the changes in the dental tissues and their environment with age have pointed out that a process commonly referred to as 'posteruptive maturation' of the dental enamel may be responsible. To test this assumption 10 unerupted third molars and 56 erupted human premolar teeth of various posteruptive ages were subjected for 130 days to an acid gel for caries-like lesion formation in vitro. Sections of the teeth were examined with polarized light and 'contour maps' were drawn with the approximate porosity of the lesions. The results were: unerupted = 833 microns (+/- 261); erupted of posteruptive age 0-3 years = 561 microns (+/- 150), 4-10 years = 470 microns (+/- 136), 11-30 years = 459 microns (+/- 192) and over 30 years = 297 microns (+/- 89). These findings show a decrease in the susceptibility of enamel to artificial caries with increasing age, which was especially marked at and shortly after eruption. This may be explained by a completion of mineralization of the outer enamel at about eruption, by a maturation process of the outer enamel posteruptively and by a reduction in the permeability of enamel occurring through to old age. The fluoride content of the mid-coronal buccal surface enamel under study was found to decrease posteruptively with age, therefore not accounting for the decreasing caries susceptibility. PMID- 1913762 TI - A study of the effect of fluoride delivered from solution and dentifrices on enamel demineralization. AB - An in vitro demineralization model has been developed and used to examine the effect of various fluoride treatments on early enamel demineralization. The effect of fluoride treatments on the calcium demineralization rate of enamel was studied by analyzing the amount of calcium which demineralized from teeth into solution when the teeth were exposed to weak acid solutions. Continuous (72 h total) exposure of enamel to very low levels of fluoride, 0.014 ppm, was observed to have a protective effect against demineralization, as was intermittent exposure to higher levels of fluoride delivered from solution and from dentifrices for shorter periods of time (40 min total). This work suggests that the residual salivary fluoride concentrations reported to be reached by water fluoridation (0.016 ppm) or brushing with a fluoride-containing dentifrice (0.014 ppm) give a level of fluoride in saliva which may give some protection to the dental enamel from demineralization. PMID- 1913763 TI - In vivo use of a dual acid etch biopsy for the evaluation of lead profiles in human surface enamel. AB - Two successive acid etch biopsies were performed on the permanent maxillary right central incisors of two age-groups of children resident in an urban area in Belgium. Lead was determined in the biopsy solutions and the concentrations were related to etch depths which were calculated from the calcium and phosphorus concentrations in the biopsy solutions. The mean lead concentration of the first enamel biopsy layer was five times higher than in the second biopsy layer. A strong relation was observed between the two biopsies. It was shown that calibration of the lead values with respect to etch depths and Ca/P ratios was desirable and that a robust regression analysis approach was needed instead of classic least-squares regression analysis. However, the second biopsy provided more reliable lead estimates. In this study no increase in lead concentration in surface enamel could be demonstrated with age. Therefore, it was concluded that for these children the presence of lead in surface enamel had to be attributed primarily to preeruptive uptake. PMID- 1913765 TI - Trehalulose does not induce dental caries in rats infected with mutans streptococci. AB - The effects of trehalulose, a structural isomer of sucrose, and a syrup (TP syrup) rich in trehalulose and palatinose on caries development were examined in specific pathogen-free Sprague-Dawley rats. Streptococcus mutans MT8148R and Streptococcus sobrinus 6715 fermented the syrup which resulted in acid production, while both strains were found not to utilize trehalulose. Furthermore, trehalulose did not serve as a substrate for glucosyltransferases of these mutans streptococci to synthesize water-insoluble glucan, and it inhibited the sucrose-dependent adherence of mutans streptococci to a glass surface. Although trehalulose induced no significant dental caries in specific pathogen free rats infected with either MT8148R or 6715, TP syrup was found to induce significant but low dental caries. Furthermore, replacement of the dietary sucrose content with trehalulose resulted in a significant reduction of caries development in rats infected with strain 6715. PMID- 1913764 TI - Effects of an acidic calcium phosphate solution and the intraoral fluoride releasing device on dental caries and fluoride uptake in rats. AB - This investigation comprised two studies evaluating the effects of an acidic calcium phosphate solution (CPS) on fluoride uptake in the enamel, glycolysis of dental plaque, the incidence of dental caries and urinary fluoride concentrations of rats wearing an intraoral fluoride-releasing device (IFRD). In the first study, CPS-fluoride treatment preceded the cariogenic challenge. In the second study, the cariogenic challenge preceded the treatments. In the first study, CPS treatments increased the ability of enamel to bind fluoride. However, the enamel bound fluoride exerted a negligible effect on plaque glycolysis as measured by the pH decrease after sucrose challenge. In the second study CPS augmented the caries inhibition for both the sulcal-morsal and buccal-lingual surfaces. In both studies the IFRD significantly restricted the development of carious enamel on the sulcal-morsal surfaces and caused elevated concentrations of fluoride in the urine independent of CPS treatments. PMID- 1913766 TI - Influence of milk, lactose-reduced milk, and lactose on caries in desalivated rats. AB - There is a growing population who suffer from hyposalivation. These patients frequently sip liquids to alleviate their discomfort. Milk appears to have many of the physical properties of a good saliva substitute. Desalivated rats given 2% milk or lactose-reduced milk remained essentially caries-free. In contrast, animals given sucrose or lactose to drink developed caries. In addition, animals given sucrose or lactose harbored significantly higher populations of Streptococcus sobrinus than did other groups. Results showed that milk and lactose-reduced milk can be used safely by hyposalivatory patients as a saliva substitute. PMID- 1913767 TI - Effect of mouthrinsing after toothbrushing with a fluoride dentifrice on human salivary fluoride levels. AB - In a recent clinical trial of sodium monofluorophosphate dentifrices, oral rinsing habits were found to influence dental caries. Thus an oral fluoride clearance study has been undertaken which was designed to test a possible mechanism for the observed effects. Eight subjects brushed with one of the trial dentifrices and then rinsed using 1 of 8 procedures of varying thoroughness. The salivary fluoride concentration measured 5 min after dentifrice application decreased significantly with increasing rinse volume, rinse duration, and rinse frequency (p less than 0.01, analysis of variance). The area under the clearance curve determined over a further 3 h was significantly higher (300%; p less than 0.01) following use of the least thorough rinsing procedure (5 ml x 2 s once) as compared with the corresponding area under the clearance curve following the most thorough procedure (20 ml x 10 s twice). These findings indicate that rinsing habits may play an important role in the oral retention of fluoride from dentifrices which may, in turn, affect their clinical efficacy. PMID- 1913768 TI - Influence of contact time and concentration of chlorhexidine varnish on mutans streptococci in interproximal dental plaque. AB - This study describes the effects of varnishes containing 0, 25, 33 and 40% chlorhexidine diacetate on mutans streptococci in human approximal dental plaque. The chlorhexidine release from the varnishes was determined in vitro. Eleven subjects participated in the clinical experiment, each with at least five approximal areas harboring high levels of mutans streptococci. The approximal areas in each of the individuals were randomly assigned to five experimental groups, in each of which one of the varnishes was tested; 40% chlorhexidine varnish was tested in two experimental groups. The varnish treatment consisted of a single application of a small amount of varnish onto the selected approximal areas. From one of the sites receiving the 40% chlorhexidine varnish, all visible varnish was removed 15 min after application. The volunteers were asked to leave the varnish on the remaining treated sites and not to brush their teeth for 8 h. All chlorhexidine varnishes strongly suppressed mutans streptococci until 4 months after the varnish application. The extent of the suppression depended upon the concentration of chlorhexidine in the varnish, 40% chlorhexidine varnish giving the greatest suppression of mutans streptococci. No significant difference was found between the numbers of mutans streptococci from sites where the 40% varnish was removed after 15 min and sites where the 40% chlorhexidine varnish was left. The results suggested that 40% chlorhexidine varnish can be used successfully for the long-term suppression of mutans streptococci. A contact time of the varnish with the tooth surface of only 15 min is sufficient to achieve this long-term suppression. PMID- 1913769 TI - Validity of diagnostic and treatment decisions of fissure caries. AB - The purpose of this in vitro study was to test the accuracy and the reproducibility of diagnostic and treatment decisions of fissure caries with and without explorer. 34 dentists were asked to diagnose 61 teeth and decide upon possible treatment. The teeth were then histologically prepared and diagnosed. The agreement between histological and clinical diagnoses was assessed. The results showed no difference in diagnostic accuracy between explorer and visual technique only. Sensitivity (62%) and specificity (84%) showed that the dentists were more likely not to treat decayed teeth than to restore sound teeth. The percentage 'correctly diagnosed teeth' was approximately 42%. As there was an inherent possibility of a correct diagnosis by chance, this value had to be corrected to 23% (kappa statistics). The percentage of 'clinically' correct treatment decisions, however, was 73%. The reproducibility test gave kappa values of 0.47 for diagnostic and 0.44 for treatment decisions. It was concluded that the use of an explorer does not improve the validity of the diagnosis of fissure caries when compared to that of a visual inspection alone. PMID- 1913771 TI - Dental caries experience in Ghana among 12-year-old urban and rural schoolchildren. AB - Children aged 12 years from two geographical regions in Ghana were examined for dental caries according to criteria of the World Health Organization. Urban and rural areas were included, the urban sample comprising 502 children attending both private (fee-paying) schools and government (non-fee-paying) schools and the rural sample 483 children attending government schools. A high proportion (78%) of the children examined were found to be caries free. The mean DMFT (decayed, missing, filled teeth) value for the urban children was 0.7 with 68% caries free, whilst that of rural children was 0.2 with 88% caries free, a statistically significant difference. Most of the caries recorded involved the occlusal surfaces of the first permanent molars, mandibular teeth being the most frequently affected. There were no missing of filled teeth among rural children. The results indicate that, compared with earlier studies in Ghana, dental caries is not increasing in this age group. The DMFT values reported here are the lowest recorded since 1968. PMID- 1913770 TI - Effect of partial substitution of invert sugar for sucrose in combination with Duraphat treatment on caries development in preschool children: the Malmo Study. AB - The aim was to study the effect of substitution of invert sugar for sucrose, in combination with fluoride varnish (Duraphat) treatment twice a year, on caries development in preschool children. One hundred and eighty-seven 4-years-olds were divided randomly into four sugar groups: (1) sucrose (S), (2) sucrose-Duraphat (SD), (3) invert sugar (I), and (4) invert sugar-Duraphat (ID). All families were asked to buy beverages, biscuits, breakfast cereals, marmalade, ice cream, jam, ketchup, sweets and table sugar, totally 32 different food items, sweetened with invert sugar or sucrose. The substitution was, thus, restricted to a number of sugar-rich between-meal products. The study was carried out double-blind for 2 years. The children of those parents who did not want to participate in the sugar groups were divided randomly into one of the following two groups: (5) Duraphat (D), and control (C). Because of lack of cooperation, only 114 of the 187 children (61%) were considered to have completed the study. The mean caries increment, including initial lesions, was 3.86 dmfs in the combined groups S and SD (n = 63) and 3.10 dmfs in the combined groups I and ID (n = 51) during the 2 years (p = 0.34). The corresponding values for the 2nd year only were 1.84 and 0.67 dmfs, respectively (p = 0.09). The mean caries increment was 2.86 dmfs in group D (n = 113) and 4.10 dmfs (p = 0.08) in group C (n = 93). If initial caries lesions were excluded from the index, the difference between groups D and C was significant (p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913772 TI - Morphological evidence for a close interaction of chromaffin cells with cortical cells within the adrenal gland. AB - The adrenal medulla appears to exert a regulatory influence on adrenocortical steroidogenesis. We have therefore studied the morphology of rat, porcine and bovine adrenals in order to characterize the contact zones of adrenomedullary and adrenocortical tissues. The distribution of chromaffin cells located within the adrenal cortex and of cortical cells located within the adrenal medulla was investigated. Chromaffin cells were characterized by immunostaining for synaptophysin and chromogranin A, both being considered specific for neuroendocrine cells. Cortical cells were characterized by immunostaining for 17 alpha-hydroxylase, an enzyme of the steroid pathway. Cellular contacts of chromaffin cells and cortical cells were examined at the electron microscopical level. In rat and porcine adrenals, rays of chromaffin cells, small cell clusters and single chromaffin cells or small invaginations from the medulla could be detected in all three zones of the cortex. Chromaffin cells often spread in the subcapsular space of the zona glomerulosa. In porcine and bovine adrenals, 17 alpha-hydroxylase immunoreactive cells were localized within the medulla. Single cortical cells and small accumulations of cells were spread throughout this region. At the ultrastructural level, the chromaffin cells located within the cortex in pig and rat adrenals formed close cellular contacts with cortical cells in all three zones. Our morphological data provide evidence for a possible paracrine role of chromaffin cells; this may be important for the neuroregulation of the adrenal cortex. PMID- 1913773 TI - Barrier membranes at the outer surface of the brain of an elasmobranch, Raja erinacea. AB - This report gives the results of the first electron-microscopic examination of the cell layers covering the outer brain surface and the inner surface of the cartilaginous skull in the skate, Raja erinacea. The perivascular glial blood brain barrier--a characteristic of elasmobranchs--extends to the outer surface of the brain. This outer barrier layer is surrounded, in turn, by a subarachnoid compartment (depth: 30-40 microns), containing loose connective tissue and blood vessels; by an arachnoid-like epithelium (10-15 cell layers), impermeable to horseradish peroxidase; and, by perimeningeal fluid, a fluid with a slow turnover rate and a protein composition different from plasma. The inside of the skull, facing the perimeningeal fluid, is covered by a multilayered (10-15 layers) cuboidal epithelium, also impermeable to horseradish peroxidase. Closely apposed cells in the luminal layer of this epithelium have apical microvilli and numerous vesicular profiles, containing material of moderate electron density. These observations may explain, in terms of structure, the regulated protein content of perimeningeal fluid and the restricted exchange of solutes between brain and perimeningeal fluid in elasmobranchs. PMID- 1913774 TI - Formation of contacts between mast cells and sympathetic neurons in vitro. AB - Functional interactions between mast cells and peripheral nerves may occur at sites of association seen in vivo. To study the interactions, we developed a tissue culture model of murine sympathetic neurons co-cultured with rat basophilic leukaemia (RBL-2H3) cells (homologues of mucosal mast cells) or rat peritoneal mast cells. In co-cultures of up to 3 days, light microscopy identified neurite contacts with peritoneal mast cells or RBL-2H3 cells, but not with glial cells or fibroblasts. Electron microscopy confirmed membrane-membrane contact between neurites and RBL-2H3 cells. Time-lapse analysis of interactions between neurons and RBL-2H3 cells showed that 60-100% of the cells in a given field acquired neurite contact within 17 h. In matching control studies, there was no increase in the frequency of neurite contact with cells of the rat plasmacytoma line (YB2/0): these were not selected as targets, and contacts were broken if formed. Time-lapse records of the derivation of neurites from their path suggested a neurotropic effect of mast cells, with neurite contact ensuing when the intervening distance was less than 36 +/- 4 microns. Once formed, contacts were invariably maintained throughout the period of examination (up to 72 h), in contrast to YB2/O or fibroblast contacts. We conclude that neurons selectively form and maintain connections with cells representative of rat connective tissue-type and mucosal mast cells in vitro. Similar interactions in vivo could promote nerve/mast cell contacts, which may allow bidirectional communication between the nervous and immune systems. PMID- 1913775 TI - Cholinergic innervation of the mouse superior cervical ganglion: light- and electron-microscopic immunocytochemistry for choline acetyltransferase. AB - The cholinergic innervation of the mouse superior cervical ganglion was investigated by means of immunocytochemistry using a well-characterized monoclonal antibody against choline acetyltransferase (ChAT). Immunopositive nerve fibers entered the superior cervical ganglion from the cervical sympathetic trunk. Light-microscopically, these fibers appeared to be heterogeneously distributed among the principal ganglion cells. The rostral part of the ganglion contained more ChAT-positive fibers then the middle or the caudal one. The axons branched several times before forming numerous varicosities. Most of the ChAT stained fibers and varicosities aggregated in glomerula-like neuropil structures that were surrounded by principal ganglion cell bodies, whereas others were isolated or formed little bundles among principle neurons. None of the neurons or other cell types in the ganglion exhibited ChAT-positivity. ChAT-immunoreactive fibers disappeared from the ganglion 5 or 13 days after transection of the cervical sympathetic trunk. At the ultrastructural level, most axon terminals and synapses showed ChAT-immunoreactivity. An ultrastructural analysis indicated that immunostained synapses occurred directly on the surface of neuronal soma (1.8%) and dendritic shafts (17.6%). Synapses were often seen on soma spines (18.4%) and on dendritic spines (62.2%). All immunoreactive synapses were of the asymmetric type. The results provide immunocytochemical evidence for a heterogeneous cholinergic innervation of the ganglion and the principal neurons. PMID- 1913776 TI - The optic lobe projection pattern of polarization-sensitive photoreceptor cells in Drosophila melanogaster. AB - Histological staining of wild-type and sevenless transgenic Drosophila melanogaster bearing Rh3-lacZ fusion genes permits the selective visualization of polarization-sensitive R7 and R8 photoreceptor cells located along the dorsal anterior eye margin. Diffusion of beta-galactosidase throughout these cells reveals that they project long axons to the two most peripheral synaptic target rows of the dorsal posterior medulla, defining a specialized marginal zone of this optic lobe. Comparison of the staining patterns of marginal and nonmarginal Rh3-lacZ-expressing photoreceptor cells in the same histological preparations suggest that the marginal cells possess morphologically specialized axons and synaptic terminals. These findings are discussed with reference to the neuroanatomy of the corresponding dorsal marginal eye and optic lobe regions of the larger dipterans Musca and Calliphora, and in relation to the ability of Drosophila to orient to polarized light. PMID- 1913777 TI - Differential distribution of beta-pigment-dispersing hormone (beta-PDH)-like immunoreactivity in the stomatogastric nervous system of five species of decapod crustaceans. AB - Pigment-dispersing hormone (PDH) acts to disperse pigments within the chromatophores of crustaceans. Using an antibody raised against beta-PDH from the fiddler crab Uca pugilator, we characterized the distribution of beta-PDH-like immunoreactivity in the stomatogastric nervous system of five decapod crustaceans: the crabs, Cancer borealis and Cancer antennarius, the lobsters, Panulirus interruptus and Homarus americanus, and the crayfish, Procambarus clarkii. No somata were stained in the stomatogastric ganglion (STG) or the esophageal ganglion in any of these species. Intense PDH-like staining was seen in the neuropil of the STG in P. interruptus only. In all 5 species, cell bodies, processes, and neuropil within the paired circumesophageal ganglia (CGs) showed PDH-like staining; the pattern of this staining was unique for each species. In each CG, the beta-PDH antibody stained: 1 large cell in C. borealis; 3 small to large cells in C. antennarius; 3-8 medium cells in P. clarkii; 1-4 small cells in H. americanus; and 13-17 small cells in P. interruptus. The smallest cell in each CG in C. antennarius sends its axon, via the inferior esophageal nerves, into the opposite CG; this pair of cells, not labeled in the other species studied, may act as bilateral coordinators of sensory or motor function. These diverse staining patterns imply some degree of evolutionary diversity among these crustaceans. A beta-PDH-like peptide may act as a neuromodulator of the rhythms produced by the stomatogastric nervous system of decapod crustaceans. PMID- 1913778 TI - Postnatal changes in the ultrastructure of the rat olfactory epithelium: the supranuclear region of the supporting cells. AB - The present electron-microscopical study reports ultrastructural changes occurring in the supranuclear region of the supporting cells of the rat olfactory epithelium during the first 16 days of postnatal life. These changes are concerned with the enclosure of receptor cell dendrites and an increase in the amount of smooth endoplasmic reticulum, which has a specific distribution in the supporting cell. An increase in microvillous projections at the free cell surface is also observed. Moreover, this report demonstrates that the cytoarchitecture of the apical portion of the olfactory epithelium at the 16th day of postnatal life is similar, with respect to the relationship between supporting cells and receptor cell dendrites, to that of adult animals. PMID- 1913779 TI - Pituitary adenylate cyclase-activating peptide (PACAP), a new vasoactive intestinal peptide (VIP)-like peptide in the respiratory tract. AB - Pituitary adenylate cyclase-activating peptide (PACAP) is a vasoactive intestinal peptide (VIP)-like peptide recently isolated from ovine hypothalami. Nerve fibers displaying PACAP immunoreactivity were found in the respiratory tract of rats, guinea pigs, ferrets, pigs, sheep and squirrel monkeys. A moderate supply of PACAP-immunoreactive fibers was seen in the nasal mucosa of guinea pigs. Few to moderate numbers of PACAP-containing fibers occurred in the tracheo-bronchial wall of rats, guinea pigs, ferrets, pigs, sheep and squirrel monkeys. The fibers were distributed beneath the epithelium, around blood vessels and seromucous glands, and among bundles of smooth muscle. In the lungs, the immunoreactive fibers were observed close to small bronchioli. A few PACAP-immunoreactive nerve cell bodies were seen in the sphenopalatine and otic ganglia of guinea pigs. Simultaneous double immunostaining of the respiratory tract of sheep and ferrets revealed that all PACAP-containing nerve fibers stored VIP. We suggest that neuronal PACAP may take part in the regulation of smooth muscle tone and glandular secretion. PMID- 1913780 TI - Effects of prolonged sodium restriction on the morphology and function of rat adrenocortical autotransplants. AB - Regenerated adrenocortical nodules were obtained by implanting fragments of the capsular tissue of excised adrenal glands into the musculus gracilis of rats (Belloni et al. 1990). Five months after the operation, operated rats showed a normal basal blood level of corticosterone, but a very low concentration of circulating aldosterone associated with a slightly increased plasma renin activity (PRA). Regenerated nodules were well encapsulated and some septa extended into the parenchyma from the connective-tissue capsule. The majority of parenchymal cells were similar to those of the zonae fasciculata and reticularis of the normal adrenal gland, while zona glomerulosa-like cells were exclusively located around septa (juxta-septal zone; JZ). In vitro studies demonstrated that nodules were functioning as far as glucocorticoid production was concerned, while mineralocorticoid yield was very low. Prolonged sodium restriction significantly increased PRA and plasma aldosterone concentration, and provoked a marked hypertrophy of JZ, which was due to increases in both the number and average volume of JZ cells. Accordingly, the in vitro basal production of aldosterone and other 18-hydroxylated steroids was notably enhanced. The plasma level of corticosterone, as well as zona fasciculata/reticularis-like cells and in vitro production of glucocorticoids by regenerated nodules were not affected. These findings, indicating that autotransplanted adrenocortical nodules respond to a prolonged sodium restriction similar to the normal adrenal glands, suggest that the relative deficit in mineralocorticoid production is not due to an intrinsic defect of the zona glomerulosa-like JZ, but is probably caused by the impairment of its adequate stimulation under basal conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913781 TI - Intraganglionic portal sinus located between small intensely fluorescent (SIF) cells and principal ganglionic neurons in the inferior mesenteric ganglion of the guinea pig. AB - The vascular system in the inferior mesenteric ganglion of the guinea pig was studied to clarify the transport pathway of transmitters released by the small intensely fluorescent (SIF) cells to the principal ganglionic neurons. Reconstruction of about 1500 1-micron-thick serial sections of the ganglion demonstrated its portal system. SIF cells were tightly packed and formed two or three clusters under the capsule of the ganglion. Branches from the inferior mesenteric artery ran directly toward these clusters and broke up into a number of coiled and looped sinusoid capillaries among the SIF cells. They then drained into a large sinus surrounding the clusters in the ganglion. Capillaries were derived from this sinus and ramified among the principal ganglionic neurons. After supplying the neurons, these vessels drained into veins surrounding the ganglion. Therefore, as we observed two distinct groups of capillaries, we call this sinus the "intraganglionic portal sinus". All the transmitters secreted from the SIF cells are collected into this intraganglionic portal sinus and are then conveyed through the capillaries to the principal ganglionic neurons. PMID- 1913782 TI - Quantitative immunogold ultracryomicrotome studies of the distribution of periimplantation proteins in the sheep. AB - Several mammalian uterine and conceptus proteins are produced at specific stages of implantation. Ovine trophoblast protein-1 (OTP-1) is only synthesised in vitro by conceptus tissue from between 13 and 21 days of pregnancy (dpc). This immunogold ultracryosection study shows that, during this period, OTP-1 immunoreactivity is only found in the Golgi body of the trophectodermal cells. A second protein, of 14 kD molecular weight (14 K protein), has a more varied distribution being found in membrane-bounded crystals in uterine epithelium and trophectodermal cells, and distributed throughout the cytosol and nucleoplasm of the uterine epithelium. There are only trace amounts of the 14 K protein in the fetomaternal syncytium which replaces the uterine epithelium during implantation, and no crystals are found in the trophectoderm after cotyledonary villus formation is initiated at 24-25 dpc. The crystals containing 14 K protein persist throughout pregnancy in the intercotyledonary areas. The narrow time window of OTP-1 occurrence reinforces the suggestion that this represents an important developmental signal, whereas the distribution of the 14 K protein indicates a more general nutritive function. PMID- 1913784 TI - Balloon valvuloplasty for mild mitral stenosis. AB - Of a total number of 288 patients with mitral stenosis treated by percutaneous balloon valvuloplasty, 21 patients had a basal mitral area equal to or greater than 1.5 cm2, as measured hemodynamically. The immediate hemodynamic results of this particular group of patients with mild mitral stenosis are described, as well as the clinical and echo doppler findings at follow-up (22 +/- 12 mo). Patients with mild mitral stenosis (group I) had more pliable valves (p less than 0.01), as assessed by echo, and higher incidence of sinus rhythm (p less than 0.02) than that observed in the remaining 267 patients (group II). After valvuloplasty the valve area increased in group I from 1.7 +/- 0.2 to 3.1 +/- 0.7 cm2 (p less than 0.0001). This mean final area was significantly different (p less than 0.0001) than that observed in group II (1.98 +/- 0.6 cm2). No patients with mild mitral stenosis developed progression of mitral regurgitation, and none had any other major complications. Most of them reached a grade I final functional status. At echo doppler follow-up studies we did not observe significant changes in the mean mitral gradient as compared with the immediate hemodynamic results. These findings suggest that early mitral balloon valvuloplasty could be an alternative in trying to favorably influence the natural course of the rheumatic mitral disease in selected patients. PMID- 1913783 TI - Calcium and ionophore A23187 stimulates deposition of extracellular matrix and acetylcholinesterase release in cultured myotubes. AB - Calcium (Ca2+) and calcium-transporting ionophores stimulate protein secretion in many cellular systems. We demonstrate here than increases in intracellular calcium concentration induce a time- and concentration-dependent deposition of extracellular matrix and an increase in acetylcholinesterase secretion. Scanning and transmission electron-microscopy revealed that treatment with the calcium ionophore A23187, or high extracellular Ca2+ levels (5 mM to 15 mM) produce significant deposits of extracellular matrix around the myotubes, as well as a marked increase in the acetylcholinesterase reaction-product. Blocking muscle contraction was not necessary for the induction of AChE secretory activity. Sucrose density-gradients of media conditioned by muscle cells revealed 3 separate acetylcholinesterase molecular forms. However, incubation with A23187 increased only the 4.5 S and the 7.2 S molecular forms, whereas the 12.0 S form showed no significant differences from controls. Polyacrylamide gel electrophoresis, and autoradiography using [3H]diisopropyl fluorophosphate revealed a broad band at 65,000 daltons. This band was broader than for controls when medium was obtained from A23187-treated cells. Our results show that increasing intracellular Ca2+ concentration induces marked deposition of extracellular matrix and increased acetylcholinesterase secretion, with an apparent selectivity for the monomeric and dimeric acetylcholinesterase molecular forms. PMID- 1913785 TI - Hemodynamic effects of prostaglandin E1 in patients with congenital heart disease and pulmonary hypertension. AB - Investigations were performed to determine whether prostaglandin E1 (PGE1) would cause a favorable change in pulmonary hemodynamics in pediatric patients with congenital heart disease and elevated pulmonary vascular resistance. Twenty-seven patients (ages 0.5 months to 19 years) were studied. PGE1 caused a significant decrease in mean pulmonary artery pressure with 0.05 microgram/kg/min and 0.1 microgram/kg/min infusions (p = .0004). There were significant increases in pulmonary blood flow (p = .0007), and decreases in pulmonary vascular resistance (p = .0001); changes in systemic pressure, resistance, oxygen consumption, and heart rate were minimal. Twenty-three patients underwent heart surgery after catheterization, nineteen of these survived. The four nonsurvivors had higher initial pulmonary resistance (PVR) and less decline in PVR with PGE1 than survivors. This study shows that PGE1 is an effective pulmonary vasodilator in patients with congenital heart disease and elevated pulmonary vascular resistance. PMID- 1913786 TI - Surgical aortic valvuloplasty using the Cavitron Ultrasonic Surgical Aspirator: an invasive hemodynamic follow-up study. AB - Valve repair and calcium debridement in patients with calcific aortic stenosis, using the Cavitron Ultrasonic Surgical Aspirator (CUSA), results in a reduction in the aortic valve gradient while potentially avoiding long-term problems inherent to prosthetic valves. Invasive followup data in these patients has not previously been reported. Ten patients in whom CUSA debridement was performed underwent cardiac catheterization prior to and 8.0 +/- 2.5 months following the procedure. Compared to baseline, the aortic valve area significantly increased from 0.75 +/- 0.2 to 1.1 +/- 0.3 cm2 (p = 0.009) and the mean gradient was significantly reduced from 54 +/- 21 to 27 +/- 21 mmHg (p = 0.02) at followup. No significant change was noted in cardiac output, ejection fraction, left ventricular end systolic or diastolic volumes or left ventricular end diastolic pressure. However, 6 patients were found to have at least one grade worsening of aortic regurgitation. The development of increased aortic insufficiency in many patients after CUSA aortic valve debridement will likely limit this procedure's clinical utility. PMID- 1913787 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: pacemaker hemodynamics. AB - The abnormal sequence of A-V contraction produces alteration of right and left heart hemodynamics reflecting the inappropriate timing of atrial contraction to ventricular filling. Some symptomatic patients may require A-V sequential pacing to improve cardiac output. The clinical effects of the atrial contribution to left ventricular function can be demonstrated by careful review of hemodynamic tracings in these individuals. PMID- 1913788 TI - Directional coronary atherectomy for failed angioplasty due to occlusive coronary dissection. AB - We describe a case in which coronary balloon angioplasty failed to improve sequential lesions and resulted in a long area of dissection between the stenoses. Directional coronary atherectomy of the occlusive dissection produced excellent angiographic improvement to achieve a successful result and avoid the need for urgent coronary bypass surgery. Directional coronary atherectomy represents a potentially useful treatment for PTCA-induced coronary dissection. PMID- 1913789 TI - Brachial rotational atherectomy. AB - The brachial approach adds a new dimension to rotational atherectomy. The two cases presented included a large ectopic right coronary artery and a right internal mammary graft where both outcomes were successful. These cases demonstrate that the brachial approach can facilitate rotational atherectomy when greater guide support is necessary. PMID- 1913790 TI - Allograft vasculopathy and death in a cardiac transplant patient with angiographically normal coronary arteries. AB - A cardiac transplant patient died of severe left ventricular dysfunction 2 weeks after coronary angiography demonstrated normal coronary arteries. Post mortem examination showed significant and diffuse allograft vasculopathy. Coronary angiography may have limited sensitivity in detecting allograft vasculopathy. PMID- 1913791 TI - Early ostial vein graft stenosis: management by atherectomy. AB - During the initial perioperative period (1 mo to 1 yr) after saphenous vein coronary grafting, early stenosis and occlusion occurs in 5-8% of grafts due to intimal hyperplasia. We report a patient who developed ostial stenosis within 4 mo of bypass surgery at the aortotomy site of two vein grafts. Balloon angioplasty of the elastic stenoses did not provide significant luminal enlargement, but successful treatment of the lesions was obtained using directional atherectomy. Histological examination demonstrated intimal hyperplasia. Directional atherectomy may be an excellent technique for treatment of elastic ostial vein graft stenoses in lieu of conventional balloon dilatation. PMID- 1913792 TI - "Hugging balloons" through a single 8-French guide: salvage angioplasty with lytic therapy in the infarct vessel of a 40-year-old man. AB - We report the a case of hugging balloons through an 8-French guiding catheter to stabilize an ectatic right coronary artery following failed thrombolytic therapy in the setting of acute myocardial infarction. Angiographic follow-up at 1 wk and 6 mo revealed persistent vessel patency. PMID- 1913793 TI - Multiple coronary artery aneurysms in an adult associated with extensive thrombus formation resulting in acute myocardial infarction: successful treatment with intracoronary urokinase, intravenous heparin, and oral anticoagulation. AB - A 37-yr-old white female was admitted to hospital with an evolving anterior myocardial infarction. Coronary arteriography revealed multiple aneurysms in the left anterior descending (and right) coronary arteries. In the left anterior descending artery, there was evidence of extensive thrombus formation. The patient was successfully treated with intracoronary urokinase, intravenous heparin, and oral warfarin. There was partial thrombolysis in 16 hr and complete thrombolysis noted 6 wk later. This case of multiple coronary aneurysms, secondary to presumed Kawasaki disease, is the first documentation of antemortem intra-aneurysmal coronary thrombosis treated successfully by thrombolytic and anticoagulant therapy. PMID- 1913794 TI - Coronary artery pseudo-occlusion associated with the use of an active hemoperfusion system during PTCA. AB - We describe the phenomenon of coronary artery "pseudo-occlusion," which may occur when active hemoperfusion devices are utilized during percutaneous transluminal coronary angioplasty (PTCA). In such cases, contrast injected via the guiding catheter fails to opacify the coronary artery distal to the tip of the dilating catheter, thereby giving the angiographic appearance of coronary occlusion. When active hemoperfusion is terminated, contrast opacifies the vessel in a normal fashion. The cause of this observation is likely multifactorial and includes obstruction to flow by the dilating catheter, high distal pressure delivered by the dilating catheter during hemoperfusion competing with the flow of contrast injected via the guiding catheter, and wash-out of contrast at the tip of the dilating catheter by non-contrast containing blood being pumped through the system. This phenomenon must be recognized if potentially deleterious repeat dilatations are to be avoided. PMID- 1913795 TI - Correlation between the position of transducers and mitral valve gradient in mitral stenosis. AB - To assess the severity of mitral stenosis related to the level of transducers, the mitral valve gradient using pulmonary wedge and left ventricle was obtained from 15 patients. The mitral gradient was obtained with both transducers at mid chest level. Then, the level of each transducer was realigned with the catheter tip in the pulmonary capillary wedge and in the left ventricle using lateral fluoroscopy and the mitral gradient was re-measured. At the mid chest level, the mean mitral valve gradient was 14 +/- 6.2 mm Hg with a mitral valve area of 1.3 +/- 0.6 cm2. With the adjusted level of transducers, the mitral valve gradient was 18.7 +/- 6.8 mm Hg with a valve area of 1.0 +/- 0.5 cm2. The difference was that the level of catheter tip in the wedge was 3.5 cm below the mid chest level and the one in the left ventricle was 2.5 cm higher than the mid chest level. This result suggested that the mitral valve gradient obtained at mid chest level underestimated the severity of mitral stenosis. PMID- 1913796 TI - Current practices in the angiographic evaluation of aortic insufficiency. PMID- 1913797 TI - Successful rotational coronary ablation following failed balloon angioplasty. AB - Rotational coronary ablation was utilized in two cases in which balloon angioplasty initially failed. In both cases, the balloon could not be fully expanded despite using high (18 Bar) inflation pressure. Rotational coronary ablation debulked the lesion, in each instance, and permitted successful balloon angioplasty to be accomplished without difficulty. These cases illustrate the point that complementary deployment of devices may not only improve the primary success of percutaneous coronary interventions, but also may widen its scope. PMID- 1913798 TI - Reduction in radiation exposure during coronary angiography. PMID- 1913799 TI - Ionic- vs- nonionic contrast agents. PMID- 1913800 TI - Outpatient pericardiocentesis. PMID- 1913801 TI - Triple mount for ceiling suspended power injectors: a real space saver. PMID- 1913802 TI - Roles of TFIID in transcriptional initiation by RNA polymerase II. PMID- 1913803 TI - Molecular and cellular origins of B lymphocyte diversity. PMID- 1913804 TI - Membrane organization of the dystrophin-glycoprotein complex. AB - The stoichiometry, cellular location, glycosylation, and hydrophobic properties of the components in the dystrophin-glycoprotein complex were examined. The 156, 59, 50, 43, and 35 kd dystrophin-associated proteins each possess unique antigenic determinants, enrich quantitatively with dystrophin, and were localized to the skeletal muscle sarcolemma. The 156, 50, 43, and 35 kd dystrophin associated proteins contained Asn-linked oligosaccharides. The 156 kd dystrophin associated glycoprotein contained terminally sialylated Ser/Thr-linked oligosaccharides. Dystrophin, the 156 kd, and the 59 kd dystrophin-associated proteins were found to be peripheral membrane proteins, while the 50 kd, 43 kd, and 35 kd dystrophin-associated glycoproteins and the 25 kd dystrophin-associated protein were confirmed as integral membrane proteins. These results demonstrate that dystrophin and its 59 kd associated protein are cytoskeletal elements that are tightly linked to a 156 kd extracellular glycoprotein by way of a complex of transmembrane proteins. PMID- 1913805 TI - Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. AB - Processing of endogenously synthesized proteins generates short peptides that are presented by MHC class I molecules to CD8 T lymphocytes. Here it is documented that not only the sequence of the presented peptide but also the residues by which it is flanked in the protein determine the efficiency of processing and presentation. This became evident when a viral sequence of proven antigenicity was inserted at different positions into an unrelated carrier protein. Not different peptides, but different amounts of the antigenic insert itself were retrieved by isolation of naturally processed peptides from cells expressing the different chimeric proteins. Low yield of antigenic peptide from an unfavorable integration site could be overcome by flanking the insert with oligo-alanine to space it from disruptive neighboring sequences. Notably, the degree of protection against lethal virus disease related directly to the amount of naturally processed antigenic peptide. PMID- 1913806 TI - A new mechanism for coactivation of transcription initiation: repositioning of an activator triggered by the binding of a second activator. AB - The cAMP receptor protein (CRP) and MaIT, the maltose regulon activator, synergistically activate transcription from the E. coli maIKp promoter. The maIKp regulatory region comprises two series of MaIT-binding sites separated by three CRP-binding sites. By combining genetic and biochemical studies, we demonstrate that the promoter-proximal region contains two overlapping sets of three MaIT binding sites. Occupation of the higher affinity set of sites, which occurs in the absence of CRP, does not lead to malKp activation. In contrast, in the presence of CRP, MalT binds to the lower affinity set of sites and triggers transcription initiation because, unlike the high affinity set, the low affinity set of sites is properly positioned with respect to the Pribnow box. The CRP effect requires the malKp-distal MalT-binding sites. The synergistic action of MalT and CRP therefore relies on MalT repositioning via the formation of a nucleoprotein structure involving the entire regulatory region. PMID- 1913807 TI - Disruption of centromere assembly during interphase inhibits kinetochore morphogenesis and function in mitosis. AB - The relationship between the kinetochore and the centromeric heterochromatin that surrounds it is unknown. Anti-centromere autoantibodies (ACAs) that recognize antigens found in the heterochromatin beneath the kinetochore disrupt mitotic events when microinjected into human cells. We show here that ACAs interfere with two different stages of centromere assembly during interphase, resulting in abnormal kinetochore structures during mitosis. Antibody injection prior to late G2 results in the subsequent failure to assemble a trilaminar kinetochore. Such chromosomes bind microtubules but are incapable of movement. Antibody disruption of events during G2 produces unstable kinetochores that prevent the normal transition into anaphase. These experiments present a novel way to examine events in the pathway of kinetochore assembly that occur during interphase, at a time when this structure cannot be visualized directly. PMID- 1913808 TI - Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae. AB - In synchronous cultures of S. cerevisiae undergoing meiosis, an early event in the meiotic recombination pathway, site-specific double strand breaks (DSBs), occurs early in prophase, in some instances well before tripartite synaptonemal complex (SC) begins to form. This observation, together with previous results, supports the view that events involving DSBs are required for SC formation. We discuss the possibility that the mitotic pathway for recombinational repair of DSBs served as the primordial mechanism for connecting homologous chromosomes during the evolution of meiosis. DSBs disappear during the period when tripartite SC structure is forming and elongating (zygotene); presumably, they are converted to another type of recombination intermediate. Neither DSBs nor mature recombinant molecules are present when SCs are full length (pachytene). Mature reciprocally recombinant molecules arise at the end of or just after pachytene. We suggest that the SC might coordinate recombinant maturation with other events of meiosis. PMID- 1913809 TI - Modifiers of position effect are shared between telomeric and silent mating-type loci in S. cerevisiae. AB - Genes placed near telomeres in S. cerevisiae succumb to position-effect variegation. SIR2, SIR3, SIR4, NAT1, ARD1, and HHF2 (histone H4) were identified as modifiers of the position effect at telomeres, since transcriptional repression near telomeres was no longer observed when any of the modifier genes were mutated. These genes, in addition to SIR1, have previously been shown to repress transcription at the silent mating loci, HML and HMR. However, there were differences between transcriptional silencing at telomeres and the HM loci, as demonstrated by suppressor analysis and the lack of involvement of SIR1 in telomeric silencing. These findings provide insights into telomeric structure and function that are likely to apply to many eukaryotes. In addition, the distinctions between telomeres and the HM loci suggest a hierarchy of chromosomal silencing in S. cerevisiae. PMID- 1913810 TI - The Drosophila plutonium and pan gu genes regulate entry into S phase at fertilization. AB - Mutations in the Drosophila maternal genes plutonium (plu) and pan gu (png) have the striking phenotype that DNA replication initiates in unfertilized eggs. Fertilized eggs from plu or png mutant mothers also have a mutant phenotype; DNA replication is uncoupled from nuclear division, resulting in giant, polyploid nuclei. Analysis of multiple alleles of these genes indicates that their wild type function is required to maintain repression of DNA replication until fertilization. The phenotype of two png alleles suggests that this gene also may play a direct role in coupling S phase and mitosis during the early cleavage divisions. We describe genetic interactions among png, plu, and the previously identified gene gnu that demonstrate these three genes regulate the same process. PMID- 1913811 TI - Subunit promiscuity among hemopoietic growth factor receptors. PMID- 1913812 TI - Processed antigen binds to newly synthesized MHC class II molecules in antigen specific B lymphocytes. AB - We describe the direct detection of radiolabeled antigen fragments bound to class II MHC molecules following immunoglobulin-mediated endocytosis and processing of native antigen in B lymphoblastoid cells. Tris-Tricine SDS gels revealed six distinct iodinated processing products that could be detected on class II MHC 1 hr after antigen endocytosis and persisted for at least 20 hr. These physiological processed antigen-class II complexes were remarkably stable, as judged by the fact that class II alpha beta dimers, which remain associated in SDS, became labeled with the same set of processed peptides. Using a lectin binding assay, we show that these physiological processing products bind to the newly maturing population of MHC molecules rather than binding to the preexisting cell surface population; in contrast, an exogenous peptide binds predominantly to the latter population. A direct T cell-independent assay for processed peptide MHC complex formation should facilitate additional studies on the exogenous antigen processing pathway. PMID- 1913813 TI - Nuclear transport of influenza virus ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibits import. AB - Because influenza virus replicates in the nucleus and buds from the plasma membrane, its ribonucleoproteins (RNPs) must undergo bidirectional transport across the nuclear membrane. Export from the nucleus to the cytoplasm was found to depend on the viral matrix protein (M1). M1 associated with newly assembled viral RNPs (vRNPs) in the nucleus and escorted them to the cytoplasm through the nuclear pores. In contrast, during entry of the virus into a new host cell, M1 protein dissociated from the RNPs, allowing them to enter the nucleus. Amantadine, an antiviral agent that induces an early block in influenza A infection, was found to block the dissociation event and thereby to prevent import of incoming RNPs into the nucleus. Together, these results showed that M1 modulates the directionality of vRNP transport into and out of the nucleus. PMID- 1913814 TI - Image reconstruction reveals the complex molecular organization of adenovirus. AB - The three-dimensional structure of adenovirus has been determined by image reconstruction from cryo-electron micrographs. Comparison with the high resolution X-ray crystal structure of hexon, the major capsid protein, enabled an unusually detailed interpretation of the density map and confirmed the validity of the reconstruction. The hexon packing in the capsid shows more extensive intermolecular interfaces between facets than previously proposed. The reconstruction provides the first three-dimensional visualization of the vertex proteins, including the penton base and its associated protruding fiber. Three minor capsid proteins that stabilize and modulate capsomer interactions are revealed. One of these components stabilizes the group-of-nine hexons in the center of each facet and the other two bridge hexons in adjacent facets. The strategic positions of these proteins highlight the importance of cementing proteins in stabilizing a complex assembly. PMID- 1913815 TI - Specific regulation of mRNA splicing in vitro by a peptide from HIV-1 Rev. AB - The Rev protein of HIV-1 regulates the synthesis of partially spliced forms of cytoplasmic viral mRNA by binding to a cis-acting RNA sequence, the Rev response element (RRE). We have investigated the regulation of splicing in vitro and have shown that Rev specifically inhibits splicing of pre-mRNAs containing an RRE by 3 to 4-fold. A synthetic peptide of 17 amino acids containing the RNA-binding domain of Rev is highly functional and specifically inhibits splicing by up to 30 fold. Other peptides that bind to the RRE with high affinity, but with low specificity, do not specifically inhibit splicing. Six repeated monomeric binding sites for the peptide can substitute for the RRE, indicating that regulation by Rev requires interactions with multiple sites. The peptide acts at a step in the assembly of splicing complexes, suggesting that one of the functions of the basic region of Rev is to prevent formation of a functional spliceosome. PMID- 1913816 TI - Increased ratio of targeted to random integration after transfection of chicken B cell lines. AB - Constructs of four different genetic loci were transfected into the avian leukosis virus-induced chicken B cell line DT40, which continues diversification of its rearranged light chain immunoglobulin gene by gene conversion. Analysis of stable transfectants revealed an unexpectedly high frequency of targeted integration into the homologous gene loci of DT40. Transcriptional activity of the target gene locus is not required, since a construct of the untranscribed ovalbumin gene also integrated predominantly by homologous recombination. A construct derived from the beta-actin locus was transfected into other chicken cell lines to determine the cell type specificity of the phenomenon. Targeted integration still occurred at high frequency in two other B cell lines that do not have the gene conversion activity. However, the ratios of targeted to random integration were reduced by at least one order of magnitude in three non-B cell lines. PMID- 1913817 TI - cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2. AB - cdc25 controls the activity of the cyclin-p34cdc2 complex by regulating the state of tyrosine phosphorylation of p34cdc2. Drosophila cdc25 protein from two different expression systems activates inactive cyclin-p34cdc2 and induces M phase in Xenopus oocytes and egg extracts. We find that the cdc25 sequence shows weak but significant homology to a phylogenetically diverse group of protein tyrosine phosphatases. cdc25 itself is a very specific protein tyrosine phosphatase. Bacterially expressed cdc25 directly dephosphorylates bacterially expressed p34cdc2 on Tyr-15 in a minimal system devoid of eukaryotic cell components, but does not dephosphorylate other tyrosine-phosphorylated proteins at appreciable rates. In addition, mutations in the putative catalytic site abolish the in vivo activity of cdc25 and its phosphatase activity in vitro. Therefore, cdc25 is a specific protein phosphatase that dephosphorylates tyrosine and possibly threonine residues on p34cdc2 and regulates MPF activation. PMID- 1913818 TI - Genetic analysis of growth cone guidance in Drosophila: fasciclin II functions as a neuronal recognition molecule. AB - fasiclin II (fas II), a member of the immunoglobulin superfamily, was previously characterized and cloned in grasshopper. To analyze the function of this molecule, we cloned the Drosophila fas II homolog and generated mutants in the gene. In both grasshopper and Drosophila, fasciclin II is expressed on the MP1 fascicle and a subset of other axon pathways. In fas II mutant Drosophila embryos, the CNS displays no gross phenotype, but the MP1 fascicle fails to develop. The MP1, dMP2, and vMP2 growth cones fail to recognize one another or other axons that normally join the MP1 pathway. During their normal period of axon out-growth, these growth cones stall and do not join any other neighboring pathway. Thus, fasciclin II functions as a neuronal recognition molecule for the MP1 axon pathway. These studies serve as molecular confirmation for the existence of functional labels on specific axon pathways in the developing nervous system. PMID- 1913819 TI - Limb regeneration: a call to arms (and legs). PMID- 1913820 TI - The Drosophila EcR gene encodes an ecdysone receptor, a new member of the steroid receptor superfamily. AB - The steroid hormone ecdysone triggers coordinate changes in Drosophila tissue development that result in metamorphosis. To advance our understanding of the genetic regulatory hierarchies controlling this tissue response, we have isolated and characterized a gene, EcR, for a new steroid receptor homolog and have shown that it encodes an ecdysone receptor. First, EcR protein binds active ecdysteroids and is antigenically indistinguishable from the ecdysone-binding protein previously observed in extracts of Drosophila cell lines and tissues. Second, EcR protein binds DNA with high specificity at ecdysone response elements. Third, ecdysone-responsive cultured cells express EcR, whereas ecdysone resistant cells derived from them are deficient in EcR. Expression of EcR in such resistant cells by transfection restores their ability to respond to the hormone. As expected, EcR is nuclear and found in all ecdysone target tissues examined. Furthermore, the EcR gene is expressed at each developmental stage marked by a pulse of ecdysone. PMID- 1913821 TI - Something old, some things new: the steroid receptor superfamily in Drosophila. PMID- 1913822 TI - The cyclophilin homolog ninaA is required in the secretory pathway. AB - In Drosophila, the major rhodopsin Rh1 is synthesized in endoplasmic reticulum (ER)-bound ribosomes of the R1-R6 photoreceptor cells and is then transported to the rhabdomeres where it functions in phototransduction. Mutations in the cyclophilin homolog ninaA lead to a 90% reduction in Rh1 opsin. Cyclophilins have been shown to be peptidyl-prolyl cis-trans isomerases and have been implicated in catalyzing protein folding. We now show that mutations in the ninaA gene severely inhibit opsin transport from the ER, leading to dramatic accumulations of ER cisternae in the photoreceptor cells. These results demonstrate that ninaA functions in the ER. Interestingly, ninaA and Rh1 also colocalize to secretory vesicles, suggesting that Rh1 may require ninaA as it travels through the distal compartments of the secretory pathway. These results are discussed in relation to the possible role of cyclophilins in protein folding and intracellular protein trafficking. PMID- 1913823 TI - ATP is required for in vitro assembly of MHC class I antigens but not for transfer of peptides across the ER membrane. AB - We have translated the HLA-B27 heavy chain in vitro and studied its assembly with beta 2-microglobulin and peptide in microsomes from human cells. The assembly process requires ATP. However, the translocation of peptide across the endoplasmic reticulum (ER) membrane does not require ATP, and binding of biotinylated peptide to BiP, an ER luminal protein, occurs after ATP depletion. Proteinase K treatment of the microsomes does not block peptide translocation. Thus, ATP is required in the lumen of the ER for efficient assembly to occur. Microsomes prepared from Raji and T1 cells show similar levels of assembly, whereas assembly in T2 microsomes is 10-fold lower. This difference remains after peptide stimulation of assembly. The inefficient assembly in T2 microsomes is not due to impaired peptide translocation across the ER membrane, as no difference was found compared with microsomes from T1 cells. Instead, the defect seems to reside in the lumen of the ER. PMID- 1913824 TI - Parallel activation of the NIMA and p34cdc2 cell cycle-regulated protein kinases is required to initiate mitosis in A. nidulans. AB - We show that in Aspergillus nidulans, p34cdc2 tyrosine dephosphorylation accompanies activation of p34cdc2 as an H1 kinase at mitosis. However, the nimA5 mutation arrests cells in G2 with p34cdc2 tyrosine dephosphorylated and fully active as an H1 kinase. Activation of NIMA is therefore not required for p34cdc2 activation. Furthermore, mutation of nimT, which encodes a protein with 50% similarity to fission yeast cdc25, causes a G2 arrest and prevents tyrosine dephosphorylation of p34cdc2 but does not prevent full activation of the NIMA protein kinase. Mitotic activation of p34cdc2 by tyrosine dephosphorylation is therefore not required for activation of NIMA. These data suggest that activation of either the p34cdc2 protein kinase or the NIMA protein kinase alone is not sufficient to initiate mitosis. Parallel activation of both cell cycle-regulated protein kinases is required to trigger mitosis. PMID- 1913825 TI - A role for the Drosophila neurogenic genes in mesoderm differentiation. AB - The neurogenic genes of Drosophila have long been known to regulate cell fate decisions in the developing ectoderm. In this paper we show that these genes also control mesoderm development. Embryonic cells that express the muscle-specific gene nautilus are overproduced in each of seven neurogenic mutants (Notch, Delta, Enhancer of split, big brain, mastermind, neuralized, and almondex), at the apparent expense of neighboring, nonexpressing mesodermal cells. The mesodermal defect does not appear to be a simple consequence of associated neural hypertrophy, suggesting that the neurogenic genes may function similarly and independently in establishing cell fates in both ectoderm and mesoderm. Altered patterns of beta 3-tubulin and myosin heavy chain gene expression in the mutants indicate a role for the neurogenic genes in development of most visceral and somatic muscles. We propose that the signal produced by the neurogenic genes is a general one, effective in both ectoderm and mesoderm. PMID- 1913826 TI - Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells. AB - The capacity of cells to organize and contract collagen fibrils is fundamental to processes as diverse as embryogenesis and wound healing. We analyzed different beta 1 integrins on diploid fibroblasts for their role in modifying the tertiary structure of collagen matrices. Using monoclonal antibodies that block the interaction of integrins with their ligands, evidence was obtained that alpha 2 beta 1 integrin is required for the contraction of a type I collagen matrix. Further supporting the role of alpha 2 beta 1, cell lines expressing minimal levels of this integrin uniformly failed to contract collagen matrices. In addition, transfection of a full-length alpha 2 cDNA into one such cell line led to enhanced cell surface expression of alpha 2 beta 1 and conferred the de novo capacity to contract collagen matrices. PMID- 1913827 TI - The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules. AB - Kallmann syndrome associates hypogonadotropic hypogonadism and anosmia and is probably due to a defect in the embryonic migration of olfactory and GnRH synthesizing neurons. The Kallmann gene had been localized to Xp22.3. In this study 67 kb of genomic DNA, corresponding to a deletion interval containing at least part of the Kallmann gene, were sequenced. Two candidate exons, identified by multiparameter computer programs, were found in a cDNA encoding a protein of 679 amino acids. This candidate gene (ADMLX) is interrupted in its 3' coding region in the Kallmann patient, in which the proximal end of the KAL deletion interval was previously defined. A 5' end deletion was detected in another Kallmann patient. The predicted protein sequence shows homologies with the fibronectin type III repeat. ADMLX thus encodes a putative adhesion molecule, consistent with the defect of embryonic neuronal migration. PMID- 1913828 TI - Handling difficult people. PMID- 1913829 TI - Pardon me, your face is showing. PMID- 1913830 TI - Tax laws: getting to know them. PMID- 1913831 TI - Financial planning: a necessary tool. PMID- 1913832 TI - Human neutrophil peptide defensins induce single strand DNA breaks in target cells. AB - To investigate whether target cell DNA injury participates in cytolysis by human neutrophil defensins (HNP), we analyzed HNP-treated cells for single strand breaks by the alkaline unwinding assay and the activation of ADPribose polymerase, a DNA repair enzyme. Strand breaks and ADP-ribosylation were first detected in K562 and Raji targets 6-8 hr after incubation with HNP and increased to maximal levels by 18 hr. DNA was not degraded into nucleosome-sized fragments. To assess the impact of DNA injury on cytolysis, we increased strand breakage by coincubating targets with HNP and two inhibitors of ADPribose polymerase, 3 aminobenzamide, or nicotinamide. Concurrently with inhibiting polymerase activity and increasing DNA injury, these agents significantly enhanced HNP-mediated cytolysis. Enhancement occurred only at time points (over 6 hr) and in targets (only nucleated targets) where HNP-induced DNA injury could be occurring. These data indicate that neutrophil defensins can induce DNA injury in targets and suggest such injury may be involved in target cell death. PMID- 1913833 TI - Interleukin-6 is constitutively produced by human CTL clones and is required to maintain their cytolytic function. AB - Maturation of cytolytic T lymphocytes from nonlytic precursors requires cytokines in addition to IL2. Interleukin-6 is the principal cytokine that cooperates with IL2 in the induction of CTL differentiation from murine and human thymocyte precursors. However, a cytotoxic differentiation factor (CDF) role of IL6 for mature T cells is challenged by data indicating that IL2 alone is sufficient for CTL generation. The aim of this study was to identify a model system in which IL6 acted as a CDF for human peripheral T cells. We noted that IL6 was endogenously produced by CTL clones in the course of their expansion with APC, lectin, and IL2. The majority of several hundred T-cell clones, both CD4+ and CD8+, produced IL6 in response to relatively high doses of IL2. Other experiments that compared the cytolytic function of CTL clones cultured in the presence of IL6 with that of the same clones cultured in the absence of IL6 demonstrated that IL6 contributes to the cytolytic ability of the majority of human CTL clones. Our data suggest that IL6 acts in an autocrine fashion to support CTL differentiation in human T cell clones. PMID- 1913834 TI - Stimulation of human T cells via anti-T cell receptor monoclonal antibody BMA031: distinct cellular events involving interleukin-2 receptor and lymphocyte function antigen 1. AB - We have analyzed activation of resting human T cells by anti-T cell receptor (TCR) monoclonal antibody (mAb) BMA031, a murine mAb of the G2b isotype. Human peripheral blood lymphocytes (PBL) respond to anti-TCR mAb by short-term proliferation in vitro and by acquisition of responsiveness to interleukin 2 (rIL 2) in the absence of detectable IL-2 production. Cell depletion and limiting dilution experiments indicate that anti-TCR mAb +/- rIL-2 stimulation covers a substantial portion of human T cells, including CD4+ and CD8+ cells. Enhancement by rIL-2 of anti-TCR mAb-induced proliferation is blocked by anti-IL-2 receptor (IL-2R, p55) mAb, while anti-TCR mAb-induced proliferation is not. In contrast, anti-TCR mAb-induced proliferation is blocked by anti-lymphocyte function antigen 1 (LFA-1, CD11a) mAb and is not demonstrable in PBL from two patients with severe congenital LFA-1 deficiency, not even in the presence of irradiated LFA-1+ PBL. We conclude that stimulation of resting human T cells by anti-TCR mAb BMA031 enables dissociation of distinct steps in T cell activation that specifically require participation of IL-2R (p55) and LFA-1 cell surface molecules in a mutually exclusive way. PMID- 1913835 TI - The inhibitory effect of human syncytiotrophoblast plasma membrane vesicles on in vitro lymphocyte proliferation is associated with reduced interleukin 2 receptor expression. AB - The mechanisms by which vesicles of syncytiotrophoblast plasma membranes (STPM) prepared from full-term human placentas inhibit lymphocyte proliferation have been investigated. In the presence of STPM, IL-2 secretion and the expression of protein P55 (IL-2R P55) from its receptor were examined in two models of PBMC proliferation: induced by PHA in 3-day-old cultures, and induced by IL-2 in 6-day old cultures. In the case of PHA stimulation, STPM strongly inhibited IL-2 (but not IL-1) secretion and IL-2R P55 expression at a concentration where lymphocyte proliferation was also blocked. In these conditions, the addition of excess recombinant IL-2 (rIL-2) only partially restored proliferation and IL-2R P55 expression. In addition, STPM inhibited proliferation and IL-2R P55 expression when resting PBMC were stimulated by a high concentration of rIL-2. These results suggest that STPM inhibit lymphocyte proliferation by affecting one or several events occurring in the synthesis and/or expression of IL-2R P55 by a mechanism which is at least partially independent of its inhibitory effect on IL-2 secretion. The significance of these results is discussed in the context of the survival of the fetal allograft. PMID- 1913836 TI - Specificity of T and B cell responses to bovine rhodopsin in Lewis rats. AB - Rhodopsin, an integral membrane protein of rod photoreceptor cells, induces an experimental autoimmune uveitis (EAU) when injected into Lewis rats. This disease is characterized by a mononuclear and polymorphonuclear cellular infiltrate of the retina resulting in destruction of the photoreceptor cells. In this study the B and T cell specificities of the response to bovine rhodopsin by Lewis rats were determined. Antibodies induced by injection of rhodopsin were directed almost exclusively to the IV-V loop (residues 174-202). Later in the response, antibody to the N-terminus was also detected. At the T cell level, most activity was directed to the C-terminus as measured by in vitro lymphocyte proliferation. Other minor T cell epitopes were found in the II-III (96-114) and IV-V (174-202) loops. Further dissection of the amino acid sequence responsible for the activity isolated to the C-terminus indicated that a 12-amino acid-long sequence (331-342) elicited the strongest proliferative response. PMID- 1913837 TI - IL-2 production by B cells stimulated with a specific antigen. AB - The ability of a specific antigen (Ag) to stimulate B cells to produce IL-2 was examined with a murine B lymphoma line, A20-HL, which expressed surface IgM specific for trinitrophenyl (TNP). The culture supernatant of A20-HL cells stimulated with TNP3.9-ovalbumin (-OVA) or anti-IgM goat IgG contained an activity which supported the proliferation of an IL-2-dependent T cell line, CTLL 2. Neither TNP3.9-OVA nor anti-IgM antibody stimulated the parent line, A20.2J, which did not bear TNP-specific sIg, whereas anti-mouse Ig rabbit IgG F(ab)2 did stimulate both A20-HL cells and A20.2J cells. The active material in the culture supernatant was identified as IL-2 based on the experiments in which the activity was inhibited by anti-IL-2 mAb, and IL-2 mRNA was expressed in A20-HL cells stimulated with TNP3.9-OVA or anti-IgM antibody. These results support the conclusion that a specific Ag can stimulate A20-HL cells to produce IL-2. For IL 2 production, TNP receptors on A20-HL cells have to be appropriately cross linked, inasmuch as either TNP3.9-OVA or TNP6.7-OVA was much more effective than TNP1.2-OVA and TNP22.9-OVA in the induction of IL-2 production by A20-HL cells. PMID- 1913838 TI - Differential effects of glutathione depletion on T cell subsets. AB - Glutathione (GSH) is known to play an important role in various lymphocyte functions. We now report that different T cell subsets express different requirements for intracellular GSH. Depletion of intracellular GSH by buthionine sulfoximine (BSO), a specific inhibitor of GSH biosynthesis, decreases the proportion of CD8+ cells (i.e., increases the CD4+/CD8+ ratio), and inhibits particularly the generation of large blast-like CD8+ cells and cytotoxic T lymphocyte (CTL) activity. CTL activity is restored by administration of exogenous GSH. Differential effects of GSH depletion were also seen at the level of individual T cell clones. The CD4+ helper T cell clone D10.G4.1.HD was found to express a high rate of interleukin 2 (IL-2) dependent DNA synthesis even after severe depletion of intracellular GSH, whereas other T cell clones including the clone 29 were severely inhibited by BSO. The results of these studies suggest that the decreased intracellular GSH levels of HIV-1 seropositive persons are probably not (directly) responsible for the selective depletion of the CD4+ T cell subset but may be responsible for a cellular dysfunction of the CD8+ subset and for the ultimate failure of the CTL to control the viral infection in these patients. PMID- 1913839 TI - Inhibition of the calpain-mediated proteolysis of protein kinase C enhances lytic activity in human NK cells. AB - Recent evidence from our laboratory has demonstrated that NK/LAK cell activation of human lymphocytes is protein kinase C (PKC)-dependent. Here, we have investigated the translocation of PKC in human NK cells exposed to sensitive targets or to PMA, a phorbol ester. In NK cells exposed to K562 for 6 hr, we observed a weak translocation of PKC whereas in NK cells exposed to PMA more than 90% of cytosolic PKC was translocated to the membrane in less than 5 min. Stimulation of NK cells with an NK-resistant target, however, did not translocate PKC even after 6 hr. Translocation of PKC to the membrane was followed by the appearance of PKM, the cytosolic calcium/phospholipid (Ca2+/PL)-independent form of PKC. The conversion of PKC to PKM was mediated by calpain, an intracellular calcium-dependent thiol proteinase. When we used two inhibitors of calpain, calpain inhibitor I (CI-I) and calpain inhibitor II (CI-II), both caused a dose related enhancement of NK-CMC when the inhibitors were present throughout the 3 hr chromium release assay. This enhancement could be circumvented by PMA or by the PKC inhibitor H-7. CI-I and CI-II added together caused a greater increase in NK-CMC than when each was added alone. CI-I and CI-II also enhanced antibody dependent cell-mediated cytotoxicity (ADCC), substantiating further our previous contention that the activation of both NK-CMC and ADCC may involve a common lytic pathway. Activation of NK cells with IL-2 for 18 hr at 37 degrees C was inhibited in the presence of CI-I. To investigate a possible feedback inhibition mechanism due to the buildup of PKC, we examined phosphatidylinositol (PI) metabolism in NK cells activated by IL-2 in either the presence or the absence of CI-I. We observed a significant decrease in PI turnover when NK cells, activated in the presence of IL-2 and CI-I, were stimulated with K562 as compared to NK cells activated by IL-2 alone, then stimulated with K562. PMID- 1913840 TI - Both interleukin-1 alpha and interleukin-1 beta are involved as accessory signals in primary antigen (tetanus toxoid) induced human T-cell activation. AB - The function of interleukin-1 alpha and interleukin-1 beta (IL-1 alpha, IL-1 beta) in tetanus toxoid (TT) induced T-cell proliferation in cultures of peripheral blood mononuclear cells (PBL) obtained from healthy donors was assessed by using neutralizing antisera to IL-1 alpha and IL-1 beta. The neutralizing capacity and the specificity of the IL-1 antisera were tested by the use of the thymoma EL-4 NOB-1 cell line. Antisera to IL-1 beta effectively neutralized the proliferative capacity of human recombinant IL-1 beta but not of human recombinant IL-1 alpha and vice versa. Addition of either anti-IL-1 beta or anti-IL-1 alpha antiserum to the culture medium hardly affected TT induced T-cell proliferation. However, the proliferative T-cell response was consistently attenuated when a combination of IL-1 alpha and IL-1 beta antiserum was used. The antisera were never capable of completely abolishing the T-cell response to TT. We conclude that (a) IL-1 alpha and IL-1 beta are both necessary accessory signals for T-cell proliferation to antigen in vitro; (b) in T-cell proliferation IL-1 alpha and IL-1 beta are interchangeable; and (c) T-cell proliferation to antigen is only partially dependent on IL-1 as signal. PMID- 1913841 TI - The response of B cells in spleen, Peyer's patches, and lymph nodes to LPS and IL 4. AB - The vast majority of B lymphocytes in the Peyer's patches (PP) and lymph nodes (LN) are memory cells or activated cells. Hence, in comparison to B lymphocytes in the spleen (SP), most B cells in these lymphoid organs have already encountered antigen. To further examine the ability of B cells in these peripheral lymphoid organs to respond to mitogens and interleukins in vitro, we have analyzed the ability of these cells (as compared to splenic B cells) to respond to LPS and LPS plus IL-4. Our results indicate that B cells from PPs and LNs proliferate poorly to LPS during the first 3 days of culture. In contrast, at later times, PP and LN B cells show enhanced proliferation as compared to splenic B cells. Furthermore, the addition of Interleukin-4 (IL-4) changes the proliferative activity of B cells from PPs and LNs, had only a minimal effect on splenic B cells. Hence, high doses of IL-4 (100 units/ml) enhance the proliferative rate of B cells from PPs and LNs early after activation, and have a suppressive effect at later times. The enhanced response of cells in PPs and LNs is further manifested by the presence of larger numbers of sIgG1+ cells 4 days after activation with LPS plus IL-4 and at 5 days these cells also secrete proportionally more IgG1 than splenic B cells. Enhanced IgG1 secretion is reflected in the methylation pattern of the s gamma 1 switch region of these cells. In cells from PP and LN cultured with LPS plus IL-4, most alleles containing the s gamma 1 region are demethylated or partly deleted, reflecting activation of this region of the Ig gene complex. In contrast, in splenic B cells, half the alleles remain in germline configuration. Our results suggest the presence of larger numbers of "preactivated" B cells in PPs and LNs as compared to spleen. These cells more rapidly secrete Ig following stimulation with LPS plus IL-4 in the absence of significant proliferation. PMID- 1913842 TI - Identification and characterization of a T cell growth inhibitory factor produced by K562 erythromyeloid cells. AB - Cells of the human erythroleukemia cell line K562 constitutively secrete a factor that inhibits human T lymphocyte proliferation induced via CD3/Ti. The factor, termed K-TIF (K562-derived T cell inhibitory factor) is produced in either the presence or absence of fetal calf serum in cultures of K562 cells and can be precipitated by 70% NH4SO4. Gel filtration chromatography on Superose 12 resin by FPLC showed that the inhibitory factor has a molecular weight of approximately 30 35 kDa. A protein of this size, metabolically labeled with [35S]methionine, specifically bound human peripheral blood mononuclear cells. Chromatofocusing with Mono P by FPLC (pH gradient 7.2-5) indicates that the inhibitory factor has an isoelectric point of 6.0-6.4. PMID- 1913843 TI - Synergistic induction of interleukin-6 production and gene expression in human thymic epithelial cells by LPS and cytokines. AB - We examined the ability of LPS and several cytokines (TNF-alpha, IL-1-beta, IFN gamma, IL-4) to modulate IL-6 production by cultured human thymic epithelial cells (TEC). IL-6 activity was measured by the hybridoma growth factor biological activity. Moderate but detectable IL-6 activity was spontaneously produced in the presence of serum proteins. LPS as well as the cytokines TNF-alpha and IL-1-beta was a potent inducer of IL-6, increasing, respectively, IL-6 levels by 9-, 28-, and 75-fold (mean values) while IL-4 and IFN-gamma provoked no significant effect. Interestingly, clearly different kinetics were observed for IL-6 induction by the various activation agents, the maximal effect being reached at 24, 48, and 72 hr, respectively for LPS, TNF-alpha, and IL-1-beta. Moreover, a synergistic effect of TNF-alpha and either LPS or IL-1-beta was observed. Indeed, TEC incubated with the cytokines in combination at optimal doses produced 5- to 170-fold more IL-6 than TEC stimulated with the cytokines individually. Neutralizing anti-IL-6 polyclonal and monoclonal antibodies completely blocked hybridoma proliferation stimulating activity of TEC supernatants; thus, implying that this activity is essentially due to IL-6. In situ hybridization analysis of cytocentrifuged TEC with an mRNA antisense probe specific for human IL-6 and labeled with 35S demonstrated that up to 90% of TEC could be induced to express the IL-6 gene. Computer-aided quantification of IL-6 mRNA levels indicated that upon stimulation with TNF-alpha combined to LPS, both the numbers of cells expressing IL-6 mRNA and the amounts of cytoplasmic IL-6 mRNA per cell were increased. Taken altogether these results demonstrate that LPS and/or cytokines can modulate and synergistically stimulate IL-6 production. In addition to a possible role in regulating normal thymic T cell activation, the IL-6 produced by TEC could be of pathophysiological relevance in disregulated situations such as in hyperplastic thymuses from patients with myasthenia gravis. PMID- 1913844 TI - Microbial production of fish (tuna) growth hormone. PMID- 1913845 TI - Fusarium oxysporum: status in bioethanol production. AB - Fermentation of lignocellulosic materials to ethanol and other solvents provides an alternative way of treating wastes and producing chemical feedstocks and fuel additives. Considerable efforts have been made in past 10 years to improve the process based on lignocellulosic biomass and hydrolysate that contains a complex mixture of sugars, decomposition products of sugars, and sometimes the inhibitory levels of soluble lignin. Despite the relative abundance of D-xylose in crop and forest residues it has not been found efficiently fermentable by most of the microorganisms. Recent research has revealed that D-xylose may be fermented to ethanol and organic acids. Recently, several strains of Fusarium oxysporum have been found to have potential for converting not only D-xylose, but also cellulose to ethanol in a one-step process. Distinguishing features of F. oxysporum for ethanol production in comparison to other organisms are identified. These include the advantage of in situ cellulase production and cellulose fermentation, pentose fermentation, and the tolerance of sugars and ethanol. The main disadvantage is the slow conversion rate when compared with yeast. PMID- 1913846 TI - Effects of chondroitin sulfate on cultured human retinal pigment epithelial cells. AB - We investigated the effects of chondroitin sulfate on growth, morphology and ultrastructure of retinal pigment epithelial (RPE) cells in culture. When added to the medium, chondroitin sulfate reduced cell density in RPE cultures in a dose dependent manner. Compared with the controls, the treated cells appeared to be larger and more granular. Electron microscopic examinations revealed accumulations of membrane-bound whorls. In addition, phagocytic activity in the treated cells was notably increased and the level of acid lipase was elevated. These data suggest that increased levels of chondroitin sulfate can induce alterations in both metabolism and activities of RPE cells. PMID- 1913847 TI - Regulation of cytoplasmic microtubule complex organisation in somatic cell hybrids. AB - Regulation of cytoplasmic microtubule complex (CMTC) organization was studied in cultured human fibroblasts and mouse macrophages by somatic cell fusion. The heterokaryons stained with antitubulin antibody had fibroblast-like CMTC even 72 hours after fusion. There was no change in CMTC pattern when more than one macrophage had fused with one fibroblast. However, the macrophage CMTC was expressed in heterokaryons when the former were located at the periphery of the heterokaryon. To evaluate the role of existing CMTC in determining the CMTC of heterokaryons, the heterokaryons were treated with nocodazole to depolymerize the CMTC and then allowed to recover. The resultant CMTC was fibroblast like. PMID- 1913848 TI - Retinoic acid does not induce formation of cilia on the surface of wound epithelial cells in axolotls. AB - It has been reported that vitamin A palmitate induces the production of cilia on the epidermal cells of the regenerating axolotl limb, and the formation of crevices in the epidermal surface. The aim of the present investigation was to reexamine under well defined conditions the potential of retinoids to evoke the above described metaplastic changes. In order to achieve our purpose we administered axolotls with retinoic acid for 2, 4, 6, 8, and 10 days after limb amputation. The young regenerates were inspected by scanning electron microscopy (SEM). The data obtained showed that the external layer of the wound epithelium and of the stump epidermis as well was quite normal without any sign of cilia formation. In some cases, crevices were observed even in control animals. PMID- 1913850 TI - Transient neuritogenesis in NB2a/d1 neuroblastoma cells induced by glial-derived protease inhibitors. AB - The initial outgrowth of neuritogenesis in mouse NB2a/d1 neuroblastoma cells may be regulated by thrombin or a thrombin-like protease, present either in serum or adsorbed to the plasma membrane, since neuritogenesis is induced by serum deprivation and treatment with the specific thrombin inhibitor, hirudin (Shea et al., 1991, J. Neurochem., 56:842). Cultured astroglial cells secrete factors that promote neuritogenesis, including protease inhibitors active against thrombin, leading to suggestions that the inhibition of specific neuronal surface proteases by the surrounding glial environment may represent an initial step in axonal outgrowth in situ. To examine the relative importance of glial-derived protease inhibitory activities on neurine outgrowth, we tested the neurite promoting effect of glial-conditioned medium (GCM) on NB2a/d1 cells. Like serum deprivation and hirudin treatment, GCM induced neurite outgrowth within 4 hr. Exogenous thrombin inhibited the effect of GCM, and cell-free enzyme assays confirmed the presence of thrombin-inhibitory activity in GCM, suggesting that GCM induces neuritogenesis by inhibition of a thrombin-like protease. Unlike neurites induced by serum removal or hirudin addition, which are rapidly resorbed following serum replenishment or hirudin depletion, however, GCM-induced neurites continued to elongate after GCM removal. Furthermore, cultures treated simultaneously with GCM and thrombin exhibited delayed outgrowth of neurites following GCM removal which were insensitive to further thrombin treatment. These findings indicate that the initial elaboration of neurites can be mediated by glial-derived protease inhibitor(s) active against a thrombin-like protease, but indicate the requirement of additional glial-derived factors for the maintenance and continued elaboration of these neurites. PMID- 1913849 TI - In vitro phosphorylation of lamin B by protein kinase C in friend erythroleukemia. Effect of chemically induced differentiation. AB - Nuclear matrix isolated from murine erythroleukemia cells (Friend cells) has been phosphorylated with gamma 32P-ATP and purified protein kinase C in order to identify specific nuclear substrates for the enzyme. HMBA has been employed to induce the cell to differentiate and to compare the changes of phosphorylation profile after erythroid differentiation. Lamin B has been found to be hyperphosphorylated by rat brain PK-C in nuclear matrix purified from uninduced cells. This difference characterizes the cells from 14 to 72 hrs of HMBA treatment and indicates that the ability of lamin B to be phosphorylated by PK-C is linked to the differentiated state. The involvement of PK-C in lamin phosphorylation might represent an early step of the signalling pathway utilized by erythroid differentiating agents to target the cell nucleus. PMID- 1913851 TI - Stimulation of erythrophagocytosis in mouse peritoneal macrophages by chondroitin sulfates: correlation with effect of phorbol esters. AB - Resident macrophages which were harvested from the mouse peritoneal cavity showed the attachment activity to opsonized erythrocytes (OE) without the treatment of chondroitin sulfates (CSA) or phorbol esters. Phorbol ester (phorbol 12-myristate 13-acetate or phorbol 12,13-diacetate) rapidly activated an opsonin-dependent erythrophagocytosis in resident macrophages, whereas CSA slowly activated it in vivo and in vitro. An additive effect of phorbol esters was observed in macrophages which were cultured with CSA in vitro or stimulated by the intraperitoneal injection of CSA for 1 or 2 day(s). In the case of macrophages stimulated by the intraperitoneal injection of CSA for 3 or 4 days the erythrophagocytic activity was at very high level and the additive effect of phorbol esters vanished. These results indicate that CSA plays a role in the induction of opsonin-dependent ingestion activity of resident macrophages. PMID- 1913852 TI - Quantification of cell nuclei isolated from hepatocytes by cell lysis with nonionic detergent in citric acid. AB - A method was developed for determining the number of nuclei of hepatocytes cultured on collagen gel using a nonionic detergent, Nikkol BO-10TX. The cells were recovered in a test tube after solubilizing the gel by incubating it with the detergent in 0.1 M citric acid and then centrifuging the mixture. Nuclei were isolated from the cells with the same detergent solution and collected by centrifugation. The numbers of nuclei in cultures, scored with a hemocytometer or an electronic particle counter, were proportional to the lactate dehydrogenase activities of the cells. This method was also applicable for scoring the number of nuclei of hepatocytes cultured on collagen-coated plastic. PMID- 1913853 TI - Evidence that the tyrosine kinase domain of a small fraction of epidermal growth factor receptor molecules is exposed on the outer surface of A431 cells. AB - Intact A431 cells were labeled with [gamma-32P]ATP. The major phosphorylation product of the ecto-kinase activity of A431 cells had the molecular mass of 170 kd and was identified as EGF receptor by specific immunoprecipitation. This phosphorylation was not stimulated by EGF added to the reaction buffer, but replacement of MgCl2 by MnCl2 in the buffer remarkably stimulated phosphorylation. An exogenous protein substrate, alpha-casein, was also phosphorylated by intact A431 cells. The analyses for phospho-amino acids of both EGF receptor and alpha-casein revealed that phosphorylation occurred mainly at phosphotyrosine residues. Tryptic phospho-peptides of the EGF receptor of intact A431 cells labeled with [gamma-32P]ATP were fractionated by HPLC. The elution patterns were essentially the same as that of the autophosphorylated EGF receptor, indicating that the phosphorylation sites of EGF receptor labeled in vivo with [gamma-32P]ATP are located in three tyrosine residues in the carboxyl terminus. These results indicate that the carboxyl-terminal tyrosine kinase domain of a small fraction of the EGF receptor molecules of an A431 cell is exposed on the outer surface of the cells. PMID- 1913854 TI - Stress fibers in situ in proximal tubules of the rat kidney. AB - Actin bundles in proximal tubules of the rat kidney were examined by immunofluorescence and confocal laser microscopy with special reference to their three-dimensional distribution and identification as stress fibers. Renal tubular segments were prepared from the fresh renal cortex by simple homogenization and centrifugation, and fixed in formaldehyde for staining with fluorescent dye labeled phalloidin. Segments of the proximal tubules could be identified easily on the bases of their diameter, the height of epithelial cells and prominent brush borders. Confocal laser microscopy clearly demonstrated the overall distribution of actin bundles in the whole-mount proximal tubular segments. Actin bundles in the basal cytoplasm of epithelial cells were observed to run parallel to each other and at a right angle to the tubular axis. In the stereo views reconstructed from serial optical sections, the basal actin bundles appeared as straight rods with both ends tapered. They varied in length and width and extended rather short distances of not more than 10 microns. Often, two or more actin bundles were longitudinally aligned in tandem. Some bundles showed irregular bandings along their length. Each bundle was composed of tightly packed actin filaments which could be decorated with heavy meromyosin subfragment-1 to display a bi-directional arrangement within the bundle. Immunostaining of cryostat sections showed that actin bundles contained myosin and vinculin. Enzymatically isolated proximal tubules contracted upon addition of Mg-ATP. These observations collectively suggest that the actin bundles at the base of renal proximal tubule epithelial cells can be listed among the examples of stress fibers in situ. PMID- 1913855 TI - The distribution and arrangement of microtubules in mammalian skeletal muscle fibers. AB - The distribution and arrangement of microtubules (MTs) in skeletal muscle fibers of the rat and mouse diaphragm were examined by thin-section electron microscopy. In the central portion of muscle fibers, most MTs ran longitudinally between myofibrils and beneath the sarcolemma, and some MTs ran transversely predominantly at the level of the I band, especially of the A-I junction, thus forming a lattice-like arrangement. At the fiber periphery, MTs were aggregated in the perinuclear region, from which they radiated to take a longitudinal course beneath the sarcolemma and to run in a transverse direction at the I-band level. In the end portion of muscle fibers, MTs were abundant and ran longitudinally into sarcoplasmic processes. MTs were often found to be spatially associated with membranous organelles. Quantitative analyses indicated that the longitudinally running MTs were remarkably more numerous in the peripheral zone of muscle fibers than in the deeper zones. The density of MTs in the central portion was almost the same in both red and white muscle fibers. The density was significantly higher at the fiber ends, though it varied considerably among different fibers. These results are discussed with special reference to the possible involvement of MTs in intracellular transport as well as structural support. PMID- 1913856 TI - An alteration in molecular form associated with activation of human heat shock factor. AB - In higher eucaryotes, heat shock factor (HSF) exists in a cryptic form in unstressed cells. We investigated molecular forms of human HSF before and after activation by sucrose density gradient centrifugation and by gel mobility shift assay using a 32P-labeled heat shock element (HSE). We found that the in vivo or in vitro activated HSF, which is capable of binding to HSE, and its inactive form present in unstressed cells have different sedimentation coefficient; the former is 8 S whereas the latter is 4-5 S. Both the 8 S and 4-5 S forms contain the HSF polypeptide which has the ability to bind to HSE upon activation. The inactive 4 5 S form acquires HSE-binding ability when activated by heat shock or other stimuli. This HSF activity was greatly reduced, however, during recentrifugation in sucrose density gradient and, in addition, the residual activity was not recovered in 8 S fractions. Transformation of the inactive 4-5 S form of HSF to the stable, active 8 S form was achieved when the inactive form was activated and mixed with cytosols of unstressed cells. PMID- 1913857 TI - [Pregnancy and obesity. II. Hormonal and metabolic changes]. AB - 28 obese women were investigated in the course of the 21st (A) and 30th (B) week of pregnancy. Increased serum levels of GH, T4 and T3 were found in both samples of blood (A and B), while serum insulin, cholesterol and triacylglycerols were increased only at time B. It was suggested that the similar increase of GH, T4 and T3 at time A and B was due to pregnancy because the level of these hormones is usually not increased in non-pregnant obese women, while hyperinsulinemia and often increased values of cholesterol and triacylglycerols are a common finding in non-pregnant obesity. This presumption was confirmed only partially--body weight and the skin folds correlated only with insulin and T3, while GH, cortisol, T4, cholesterol and triacylglycerols correlated only exceptionally. High levels of insulin and T3 may be due to overeating. PMID- 1913858 TI - [Epidemiology and diagnosis in the vaginal environment. III. Diagnosis and epidemiology of bacterial vaginosis]. AB - In a group of 600 examined women clue cells were detected in the native preparation in 72 women (12%), a positive amine test was recorded in 81 women (13.5%). 93.1% patients (67) with the finding of clue cells had a positive amine test. The values of the vaginal pH vary between 4.8 and 5.5. According to the accepted diagnostic concept bacterial vaginosis was detected in 68 women (11.5%). The most frequent concurrent infection was trichomoniasis. Finally the authors recommend to transfer the diagnosis of vaginal discharge from laboratories to surgeries, from fixed stained smears to native smears supplemented by the amine test and assessment of vaginal pH. PMID- 1913859 TI - [Mycoplasmas in the vaginal flora in colpitis]. AB - The vaginal secretion of 194 women was subjected to bacteriological examination. The results of cultivation examinations were compared with MOP examinations. The widest bacterial spectrum was recorded in MOP II. No differences were recorded as regards detection of lactobacilli and potentially pathogenic bacteria in MOP I, II and III. The percentage of women with Ureaplasma urealyticum was equal in case of MOP I, II and III. Mycoplasma hominis was isolated significantly more frequently in MOP II than in MOP III. As compared with results of examinations in asymptomatic women, those with colpitis were significantly less frequently colonized with Ureaplasma urealyticum and Mycoplasma hominis. The authors did not record any differences in the composition of the microbial flora in women colonized with mycoplasmas and those without mycoplasmas. PMID- 1913860 TI - [Onset of menarche and the course of menstrual cycles in female athletes in Youth Training Centers in Slovakia]. AB - The authors characterize girls in youth Training Centres in Slovakia from the medical anthropometric, somatotypological and locomotor aspect and recorded the time of menarche and course of the menstrual cycle. 1. The group comprised 107 girls, mean age 13.69 years who specialized in different sports: tennis players, skiers (cross country skiing), high mountain skiers, synchronized swimmers, gymnasts, swimmers. 2. The mean daily load was 4-5 hours and together with competitions during weekends 800 hours per year. 3. Tennis players, gymnasts and swimmers started regular training at preschool age and the time of menarche varied. At an age above 12.5 years menarche was not recorded in high mountain skiers and swimmers. At a mean age above 13 menarche was recorded in tennis players, synchronized swimmers and gymnasts but not always in the whole group. The latest time of menarche was recorded in cross country skiers. In the menstrual cycle regularities and irregularities, dysmenorrhoea, premenstrual tension and sacralgia were recorded. As some girls did not enter menarche yet it is not possible to evaluate conclusively the influence of intensive physical training on the organism of girls. 4. The authors compared all assembled results with results in the available literature. 5. The authors proceed with the described investigations. PMID- 1913861 TI - [Grand multiparity--is it still an obstetrical problem?]. PMID- 1913862 TI - [The pessary in the treatment of vaginal and uterine prolapse and descent--a gynecologic atavism?]. PMID- 1913863 TI - [Evaluation of the Cech-Mojzisova method of rehabilitation therapy in functional female sterility]. PMID- 1913864 TI - [2 cases of simultaneous pregnancies]. PMID- 1913865 TI - [Combined intrauterine and extrauterine pregnancy--a rare, potentially dangerous diagnosis]. PMID- 1913867 TI - [Specifics in the experience of childbirth via cesarean section]. PMID- 1913866 TI - [Mechanisms of labor onset]. PMID- 1913869 TI - [Selection of sex of the child as a possible goal of family planning]. PMID- 1913868 TI - [Induced abortion--history, present status and perspectives]. PMID- 1913870 TI - [Tibolone--a new steroid for therapy of the climacteric syndrome and prevention of osteoporosis]. PMID- 1913871 TI - [Recommendations for the prevention and therapy of disorders of hemostasis in pregnancy and the postpartum period]. PMID- 1913872 TI - Regulation of the pyrimidine salvage pathway by the FUR1 gene product of Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, the protein encoded by the FUR1 gene is absolutely required for the expression of uracil phosphoribosyl transferase activity. The occurrence of semi-dominant mutations for 5-fluorouracil-(5FU)-resistance at this locus led us to clone and sequence the semi-dominant fur1-5 allele. A single point mutation, resulting in the substitution of arginine 134 for serine, is responsible for this mutant phenotype. The fur1-5 allele is transcribed and expressed at the same level as the wild-type allele. But, in contrast with the wild-type, the UPRTase activity of the fur1-5 mutant strain is stimulated in vitro by UTP and does not, therefore, correspond to a loss of feedback of UPRTase activity. We found that uracil, as a free base, induces a significative increase in transcription and UPRTase activity in a wild-type strain as well as in uracil overproducing mutants which principally explains the high efficiency of the pyrimidine salvage pathway in S. cerevisiae. PMID- 1913873 TI - The gene DIS2S1 is essential in Saccharomyces cerevisiae and is involved in glycogen phosphorylase activation. AB - S. cerevisiae gene DIS2S1, which codes for a protein very similar to the catalytic subunit of mammalian protein phosphatase 1, was disrupted "in vitro". Diploid yeast cells were transformed and sporulated. Tetrad analysis demonstrated that disruption of DIS2S1 is lethal for the cell. Glycogen phosphorylase alpha and glycogen synthase activity ratio were measured in diploids carrying a disrupted allele of the gene. Phosphorylase was dramatically activated in mutant cells but, under the same conditions, glycogen synthase activity was essentially identical in both mutant and wild-type cells. PMID- 1913874 TI - Cycloheximide resistance as a yeast cloning marker. AB - In CYH2/cyh2 heterozygous diploids of the yeast Saccharomyces cerevisiae resistance is dominant over sensitivity at low (0.5-5 micrograms/ml) cycloheximide (cyh) concentrations. The cyh-resistant haploid strain MMY1 confers relatively high (10 micrograms/ml) cyh-resistance to heterozygous diploids constructed by mating this strain with cyh-sensitive haploid strains. We present here a genetic and biochemical study of strain MMY1. Analysis of tetrads obtained from a MMY1 heterozygous diploid showed that two unlinked nuclear mutations, determining high- and low-cycloheximide resistance, were present in MMY1. From a genomic library of this strain, constructed in vector YCp50, two plasmids (pRC1 and pRC13) have been isolated which, respectively, confer high- and low resistance phenotypes to cyh-sensitive S. cerevisiae strains. The restriction maps of pRC1 and pRC13 are totally unrelated. This finding suggests that the genes harboring the two mutations encoding cyh-resistance from MMY1 were cloned in plasmids pRC1 and pRC13, respectively. Pulse field gel electrophoresis showed that the DNA insert of pRC1 maps at either chromosome VII or XV, whereas that from pRC13 maps at chromosome XI. This latter gene appears to define a previously unreported locus and has been named cyh5. By restriction and nucleotide sequencing analysis, the cyh gene present in pRC1 has been shown to correspond to cyh2, which maps at chromosome VII. These results suggest that the dominant cyh resistance phenotype conferred by MMY1 in heterozygous diploids is promoted by the presence of both cyh2 and cyh5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1913875 TI - Isolation of uridine auxotrophs from Trichoderma reesei and efficient transformation with the cloned ura3 and ura5 genes. AB - Uridine auxotrophs of the filamentous fungus Trichoderma reesei have been selected using a positive screening procedure with 5-fluoro orotate. Mutants deficient for the orotidine-5'-phosphate decarboxylase gene (ura3 mutants) and for the orotate phosphoribosyl transferase gene (ura5 mutants) have been characterized. The homologous ura3 and ura5 genes have been isolated and used to transform the auxotrophic mutants. Transformation efficiency with these homologous systems is very high (greater than 10(4) transformants per micrograms DNA). Transformation occurred by integration of vector DNA at homologous and ectopic loci. Mitotic instability was observed among some of the transformants. Sequence analysis at the protein level, of the T. reesei ura3 and ura5 genes showed extensive blocks of homology, with the corresponding genes from other organisms. The ura3 gene from T. reesei contains an insertion of 103 aa. A similar sequence is also found inserted in OMPdecase from the pyrenomycetes Neurospora crassa and Cephalosporium acremonium. PMID- 1913876 TI - Cloning and nucleotide sequence of the genomic ribonuclease T2 gene (rntB) from Aspergillus oryzae. AB - Using synthetic oligonucleotide probes, we have cloned a genomic DNA sequence encoding a ribonuclease (RNase) T2 gene (rntB) from Aspergillus oryzae on a 4.8 kb HindIII fragment. DNA sequence analysis of the RNase T2 revealed the following: (1) The gene is arranged as five exons and four introns; (2) The deduced amino acid sequence contains 239 amino acid residues of the mature enzyme. In addition, there exist 17 amino acid residues thought to be a signal peptide sequence at the N-terminus and 20 amino acid residues at the C-terminus; (3) The nucleotide sequence of the rntB gene is homologous to those of the RNase Rh gene from Rhizopus niveus and the S2 stylar glycoprotein gene of Nicotiana alata with degree of about 51% and 47%, respectively; (4) A. oryzae and A. nidulans transformed with the cloned rntB gene had much higher ribonuclease T2 activity than wild-type strains. PMID- 1913877 TI - Molecular cloning and characterization of two distinct hsp85 sequences from the steroid responsive fungus Achlya ambisexualis. AB - In Achlya ambisexualis, hsp85 is one of the characteristic mycelial heat shock proteins induced in response to a rapid elevation in temperature (Silver et al. 1983). This heat shock protein has the same electrophoretic mobility on two dimensional gels and is antigenically related to an 85 kDa steroid hormone regulated protein which constitutes a component of the putative Achlya steroid hormone-receptor complex. We report here the isolation of two distinct, yet highly related, hsp85 gene sequences from Achlya genomic libraries. Northern analyses, using these two Achlya genomic sequences as probes, suggest that there are two hsp85 message population in Achlya and that at least one of these is regulated by the steroid hormone antheridiol. PMID- 1913878 TI - Linear DNA plasmids of Pichia inositovora are associated with a novel killer toxin activity. AB - Pichia inositovora, strain NRRL Y-18709, which contains three linear double stranded DNA plasmids, pPinl-1, pPinl-2 and pPinl-3, was cured of these plasmids both by growing the strain in the presence of 50 micrograms/ml bisbenzimide, and by exposure to ultraviolet light. Both cured and uncured strains were tested for growth on a variety of carbon sources. No differences in growth response were detected, indicating no discernible involvement of the linear plasmids in the catabolism of these compounds. Culture supernatants of Pichia inositovora were shown to contain a substance larger than 100 kDa that is toxic to Saccharomyces cerevisiae, strain GS 1688. Toxin activity was optimal in YEPD assay plates containing 50 mM citrate buffer with a pH between 3.4 and 4.2. Culture supernatants from P. inositovora were also weakly active against Cephaloascus albidus, strain NRRL Y-18710, and Citeromyces matritensis, strain NRRL Y-18711. Concentrated supernatants from cured P. inositovora strains did not exhibit these activities, consistent with the hypothesis that this toxic activity is linear plasmid-encoded. Unlike the well-known Kluyveromyces lactis system, or the newly identified P. acaciae system, P. inositovora strains cured of their linear plasmids do not become detectably sensitive to toxin produced by the wild-type strain suggesting a nonplasmid-encoded immunity function. PMID- 1913879 TI - Pea chloroplast genes encoding a 4 kDa polypeptide of photosystem I and a putative enzyme of C1 metabolism. AB - The nucleotide sequence of 3.2 kbp of pea chloroplast DNA located upstream from the petA gene for cytochrome f, and previously reported to contain the gene for a photosystem I polypeptide, has been determined. Three open reading frames of 587, 40 and 157 codons have been identified. Orf40 encodes a highly conserved, hydrophobic, membrane-spanning polypeptide, and is identified as the gene psaI for the 4 kDa subunit of photosystem I. Orf587 is an extended version of the gene zfpA previously identified as encoding a conserved putative zinc-finger protein. The product of orf587 shows extensive homology to an unidentified open reading frame cotranscribed with a gene for folate metabolism in Escherichia coli and local homology to a region of the beta subunit of rat mitochondrial propionyl-CoA carboxylase. It is suggested that the product of orf587 is an enzyme of C1 metabolism and is unlikely to be a regulatory DNA-binding protein. Orf157 potentially encodes an unidentified basic protein, but the protein sequence is not conserved in other plants. PMID- 1913881 TI - [Clinico-genetic aspects of retinoblastoma. I. Principles of etiologic diagnosis of retinoblastoma]. AB - The author presents his own experience with assessment of the aetiology of retinoblastoma in 35 affected families. He analyzed 14 clinical and genetic indicators which confirmed heredity in 18.4% of unilateral retinoblastomas and in 100% bilateral retinoblastomas. The results of the aetiological diagnosis were used to improve genetic consultations. PMID- 1913882 TI - [Assessment of vision using a computer]. AB - 1. The authors elaborated and tested a computer method for assessment of vision. This method is compatible with the basic procedure for assessment of vision and its variability. 2. The authors recommend to supplement values of vision by the parameter of line steepness. This parameter is independent on the value of vision and gives the number of normalized lines on which the number of correctly assessed optotypes declines from 95 to 5%. PMID- 1913880 TI - A small gene family in barley encodes ribosomal proteins homologous to yeast YL17 and L22 from archaebacteria, eubacteria, and chloroplasts. AB - The amino acid sequences of two barley ribosomal proteins, termed HvL17-1 and HvL17-2, were decoded from green leaf cDNA clones. The N-terminal sequences of the derived barley proteins are 48% identical to the N-terminal amino acid sequence of protein YL17 from the large subunit of yeast cytoplasmic ribosomes. Via archaebacterial ribosomal proteins this homology extends to ribosomal protein L22 from eubacteria and chloroplast. Barley L17, and ribosomal proteins L22 and L23 from the archaebacteria Halobacterium halobium and H. marismortui, are 25-33% identical. Interestingly, the barley and archaebacterial proteins share a long, central stretch of amino acids, which is absent in the corresponding proteins from eubacteria and chloroplasts. Barley L17 proteins are encoded by a small gene family with probably only two members, represented by the cDNA clones encoding HvL17-1 and HvL17-2. Both these genes are active in green leaf cells. The expression of the L17 genes in different parts of the 7-day old barley seedlings was analyzed by semiquantitative hybridization. The level of L17 mRNA is high in meristematic and young cells found in the leaf base and root tip. In the leaf, the L17 mRNA level rapidly decreases with increasing cell age, and in older root cells this mRNA is undetectable. PMID- 1913883 TI - [Retinal detachment after perforating injuries of the eye. I. Analysis of anamnestic data related to the injury, analysis of deficiencies in the primary care of the eye injury and principles of prevention of post-traumatic retinal detachment]. AB - In 1977-1987 the authors operated by the cryosurgical method 69 patients on account of detachment of the retina. The detachment occurred in 37 patients after simple perforation of the eye and in 32 patients after perforation with a foreign intraocular body. In all patients the perforation penetrated as far as the vitreous body. In the first part of the paper the authors analyze in detail anamnestic data related to the injury: age, mechanism of injury, rapidity and method of surgical treatment, chemical nature of foreign body and its size, rapidity and method of extraction of the foreign body. In the subsequent part the authors define the principles of prevention of post-traumatic detachment of the retina during surgical treatment of the injury. Finally the basic shortcomings of primary treatment of the injury from the aspect of detachment of the retina are outlined, as recorded in the group treated by the authors. PMID- 1913884 TI - [Retinal detachment after perforating eye injuries. II. The interval between injury and retinal detachment and factors which may have contributed to the development of retinal detachment]. AB - The authors operated in 1977-1987 by the cryosurgical method 69 patients after injuries on account of detachment of the retina. Detachment developed in 37 patients after simple perforation of the eye and in 32 patients after perforation of the eye with a foreign intraocular body. In all patients the perforation reached as far as the vitreous body. The interval injury--detachment was assessed retrospectively. The authors found that for the development of post-traumatic detachment of the retina a period of two years after the injury is decisive- within this period detachment of the retina occurred in 55% of the cases. Another 31.9% of the cases occurred during the late post-traumatic period, i.e. 6-40 years after injury. In 21.7% patients anamnestic data were found which were, no doubt, associated with the detachment of the retina: surgical trauma in 8.7%, direct contusion of the eye in 10.1% and lifting a heavy burden in 2.9%. PMID- 1913885 TI - [Retinal detachment after perforating eye injuries. III. Analysis of retinal detachment after perforating eye injuries and determination of the characteristics of the retinal detachment after perforating eye injuries]. AB - In 1977-1987 the authors operated, using the cryosurgical method post-traumatic retinal detachment in 69 patients. Retinal detachment developed in 37 patients after simple perforation of the eye by a foreign intraocular body. In all patients the perforation penetrated as far as the vitreous space. In patients with retinal detachment the authors investigated the following: the patient's age, refraction, period of retinal detachment, extent of retinal detachment, the state of the macula, the characteristics of the retinal defect (site, size and number), type of retinal detachment and associated adverse factors. In the characteristics of retinal detachment after perforating eye injuries the first place was held by prognostically adverse vitreous traction in 73.9%. PMID- 1913886 TI - [Types of microsurgical technics for extraction of foreign bodies from the anterior chamber]. PMID- 1913887 TI - [The Pulsair manual noncontact tonometer]. AB - The authors present a report on their own experience with a manual contact-free tonometer Pulsair of Keeler Co. Ais compared with results obtained by means of the manual aplanation Perkins tonometer of Clement Clarke International Ltd. in the group of patients with IOP under 2,8 kPa the arithmetic means of four readings, the scatter of mean values and standard deviations assessed by both methods were not significant. Correlation coefficient 0.92 (p less than 0.001). In the group of patients with glaucoma and hypertonics with IOP of 2.93 kPa and more the arithmetic means of four readings were significantly higher (at the 1% level) in contact-free tonometry. Correlation coefficient 0.95 (p less than 0.001). The authors emphasize the main advantage of the contact-free manual tonometer: safety, rapid procedure, objectivity, accuracy, manual use. PMID- 1913888 TI - [Decentration of posterior chamber intraocular lenses]. AB - In a group of 300 patients with a posterior chamber lens in 19% its decentration was found, in 2.3% the iris capture syndrome. The author discusses possible causes of decentration of the implanted lens, possibilities of its therapy. PMID- 1913889 TI - [Visual function requirements in modern aviation]. AB - The authors describe aviation ophthalmology as a typical ergoophthalmic discipline as regards the sphere of interest as well as with regard to its preventive trend. The visual analyzer is a very exposed sense which can be modified by some dynamic effects of flight to such an extent that they may restrict the pilot's activities and consequently also the safety of the flight. Specific factors of flight which comprise also aerogenic hypoxia, hypobarism, overloading, vibrations and the consequences of impaired relations of the different senses may be manifested by changes of the perception of light, colour, visual acuity, perception of contrasts of the visual field etc. The most modern aviation technique puts some so far unusual demands on vision tested by means of complicated psychophysiological tests. Only the future will show which tests should be included among routine methods of aviation ophthalmology and which tests will be restricted only to experimental work. PMID- 1913890 TI - [The role of the community ophthalmologist in the care of severe visual defects]. PMID- 1913891 TI - [Clinico-genetic aspects of retinoblastoma. II. Genetic consultation in 35 families with retinoblastoma]. AB - The author presents a genealogical analysis of 35 families suffering from retinoblastoma and uses the results of the aetiological diagnosis to assess more accurately the ratio of heredity in the aetiology of retinoblastoma. All families received genetic consultation and the family-history was studied from the genetic and clinical aspect. The authors discuss different situations encountered during genetic consultations and outline new possibilities of screening of retinoblastoma by using discoveries of molecular genetics. PMID- 1913892 TI - [Implantation of retropupillary intraocular lenses in post-traumatic conditions of the eye]. AB - The investigation comprises the results of post-traumatic artephakias. In the course of 15 months the authors treated 15 patients with traumatic cataract after previous perforating or blunt eye injuries. In 12 patients after extracapsular extraction a retropupillary IOL was implanted. In three patients implantation was not performed. Retropupillary pseudophakia is the optimal correction of aphakia even in patients with previous serious eye injuries. A higher incidence of postoperative complications may be expected. PMID- 1913893 TI - [Evaluation of the questionnaire on ambulatory ophthalmology]. AB - The authors evaluate the questionnaire programme "Ambulatory ophthalmology". They draw attention to working problems of the ambulatory doctor and submit some suggestions to improve the position. They try to activate ophthalmologists for collaboration and more rapid essential changes. PMID- 1913894 TI - [Presbyopia and eyeglasses]. PMID- 1913895 TI - [Ultrastructural changes in the vitreous body in diabetic retinopathy]. AB - The authors investigated by transmission electron microscopy bioptic specimens obtained during pars plana vitrectomy. In the findings phagocytozing cells predominate. Due to cell damage accurate typing is difficult. The authors discuss the causes and extent of cellular damage. From morphological findings the conclusion can be drawn that in the histological picture macrophages, hyalocytes and damaged collagen fibrils predominate. PMID- 1913896 TI - [Glaucoma in the Czech Republic]. AB - The authors investigated the conditions for the diagnosis and treatment of glaucoma in the Czech Republic using questionnaires dispatched to 88 departments. The total number of patients suffering from glaucoma is 50,000, the highest rate being in Prague and Moravia (a 9,000). In relation to the number of population the frequency is greatest in Prague (1 per 140 population) and lowest in Southern Bohemia (1 per 318). In 12 departments routine gonioscopic examinations are not made, in 30 departments applanation measurements of the intraocular pressure are not made. Statistical computed perimetry can be performed only in six departments. In 1989 about one tenth of the total number of 9,000 patients hospitalized on account of glaucoma were hospitalized on account of acute glaucoma. In that year 952 primary and 320 secondary glaucomas were operated, the greatest number in Prague and Eastern Bohemia. It is essential to improve the standard of ambulatory diagnostic and therapeutic care at the expense of hospital admissions. PMID- 1913897 TI - [Toxic damage of the optic nerve in treatment with ethambutol in a patient on chronic dialysis]. AB - The authors give an account of a 57-year-old male patient who was regularly dialyzed for two years and treated because of suspect TB of the spine with antituberculotics, incl. ethambutol. In the course of 8-9 months he was given 17.9 mg/kg ethambutol per day. Because of the practically zero excretion by the damaged kidney the drug cumulated in the serum and reached toxic levels before dialysis. Gradual deterioration of eyesight developed (central acuity and colour sense) which resulted in bilateral atrophy of the optic nerves with concentric narrowing of the visual field. PMID- 1913898 TI - [Contrast sensitivity in aphakia and artiphakia]. AB - Examination of the contrast sensitivity in aphakic eyes corrected by glasses and in artephakias provides information which cannot be obtained by measurement of visual acuity and is thus a suitable supplement of the basic test of visual functions. Contrast sensitivity declines significantly with advancing age. Contrast sensitivity of aphakic eyes corrected by glasses corresponds to values of contrast sensitivity of phakic eyes of the same age group. Artephakias with an iris clip lens have a contrast sensitivity reduced by cca one half as compared with a control group, while in artephakias with a posterior chamber lens there is a decline by one third, as compared with a control groups of the same median age. PMID- 1913899 TI - [Accuracy of ultrasound measurements of the axial length of the eye]. AB - Ultrasonic assessment of the axial length of the eye provides important baseline data for the calculation of the dioptric power of an artificial intraocular lens. The accuracy of ultrasonic biometry performed by an OPHTASCAN B apparatus is discussed based on evaluation of a group of repeated measurements of the axial length and depth of the anterior chamber in 592 bulbi. PMID- 1913900 TI - [Reliability of the SRK formula]. AB - The authors investigate the postoperative dioptric deviation from the calculated dioptric power of emetropic intraocular lenses by means of the SRK formula. The deviation varied in 82% of the operated eyes within the range of +/- 1.5 D. More accurate calculations were achieved in a group of eyes with a normal axial length of the eyeball (22.0 to 24.5 mm). The authors discuss also circumstances which influence the accuracy of calculation according to formula SRK (assessment, calculation) and factors participating in the final postoperative refraction (different surgical techniques). PMID- 1913901 TI - [Pars plana vitrectomy in the treatment of exogenous suppurative endophthalmitis]. AB - The authors evaluate the results of pars plana vitrectomy (PPV) in 12 patients with exogenous suppurative endophthalmitis (EHE). EHE developed after operation of cataract in eight patients and after perforating injury of the sclera in four patients. The shape, size and appearance of the eye was preserved in 11 eyes, the function of the eye with a visual acuity of 0.5-1.0 was saved in six eyes (50%), in one eye with bacteriologically confirmed mycotic enophthalmitis and in five eyes where bacterial infection was assumed. Inoperable detachment of the retina characterized the ophthalmoscopic finding in all eyes with loss of function. Close cooperation of ophthalmological departments with vitreoretinal centres and early performance of urgent surgery are the basic prerequisites of better functional results of PPV in EHE. PMID- 1913903 TI - [Changes in the electroretinogram in diabetes mellitus]. AB - The authors deal with the relationship between changes of components of the electroretinogram, i.e. their reduction, and the degree of affection of the retina in diabetes mellitus. The group of 145 examined subjects was divided into 5 sub-groups with regard to the severity of retinal affection, and electroretinographic examinations were made. For evaluation logistic functions and other statistical methods were used. From the results it was concluded that the validity of the relationship applies only to advanced affections of the retina, while in early cases this relationship is uncertain. PMID- 1913902 TI - [Pars palana vitrectomy in chronic uveitis]. AB - The authors evaluated the results of pars plana vitrectomy (PPV) on account of chronic uveitis in 10 eyes of nine patients. In one patient where both eyes were operated on the cause of uveitis was spondylitis ankylopoietica, in the remainder the cause of uveitis was not revealed. All eyes tolerated PPV well. PPV markedly improved the visual acuity in 7 eyes (70%), a visual acuity of 1.0-0.7 was recorded in three eyes, an acuity of 0.4-0.1 also in three eyes and an acuity of 0.04 in one eye. The cause of failure in all instances was detachment of the retina. PPV is an obvious asset in the treatment of chronic uveitis associated with thick exudation into the vitreous body. PMID- 1913904 TI - [Retinal detachment in pseudophakia]. AB - In a group of 2,281 eyes after extraction of a cataract and implantation of an iris clip lens (1,362 eyes after intracapsular extraction and 927 eyes after extracapsular extraction) motion of the retina occurred in 36 eyes (1.67%), incl. 27 after intracapsular extractions (1.98%) and 9 after extracapsular extractions (0.97%). In patients with pseudophakic retinal detachment after implantation of an iris clip lens the frequency of factors which might interfere with the development of this complication was investigated. The latter proved to be the following: prolapse of the vitreous body, luxation of the implanted lens, posterior uveitis and myopia. Detachment of the retina was preceded by: peroperative prolapse of the vitreous body in 34.21%, luxation of the implanted lens in 28.95%, posterior uveitis in 36.85% and myopia (up to -4.0 Ds) in 21.05%. Anatomical and functional results after operation of pseudophakic motion were evaluated in 38 eyes (36 eyes operated on account of cataract in the authors' department, two in other departments). The minimal follow up period after operation of retinal detachment was six months. Anatomical restoration of the retina was achieved in 23 eyes (60.53%), in 9 eyes a residual motion remained (23.68%) and in four eyes total motion (10.53%). In two eyes keratopathy developed (5.26%). Central vision 6/6-6/12 was achieved in 18.42%, 6/15-6/36 in 21.05%, 6/60-3/60 in 28.95% and less than 3/60 in 31.58%. In the poorer anatomical and functional results after operation of pseudophakic motions participate in addition to the above mentioned ones difficult visualization of the retinal periphery and the extent of surgical trauma during surgery of detached retinas. PMID- 1913905 TI - [Epikeratophakia--our initial experimental approaches]. AB - The authors submit information on the contemporary state of epikeratophakia in the world. They mention its advantages, surgical technique and initial experimental results. They pay also attention to problems associated with its introduction into clinical practice in this country. PMID- 1913906 TI - [Imaging and computer processing of the ocular fundus picture]. AB - Computer analysis of a picture in ophthalmology makes objective evaluation of the clinical finding possible. After analogue-digital transfer the pictures of the fundus on a black and white negative and coloured positive 24 x 36 mm were analyzed on a Pericolor 2000 E computer. We measured the area of the glaucoma excavation of the papilla of the optic nerve, calculated the C/D ratio, assessed changes in the picture of the fundus in exudative diabetic maculopathy on paired slides obtained after a one-year interval. We evaluated changes of fluorescein penetration during fluoroangiography in different diseases. PMID- 1913907 TI - [Ocular changes in the Williams-Beuren syndrome]. AB - One of the signs of Williams-Beuren syndrome are typical opthalmological findings. In a group of 13 patients with this disease, in 7 esotropia was detected, in 8 a star-shaped iris and in 9 hyperopia. Three children had yellowish opalescent spots in the stroma of the cornea and in one patient cataracta punctata was found. A tortuous course of the retinal vessels was found in three patients, incl. two with elevated arterial pressure. Detection of these ophthalmological changes can contribute to the correct diagnosis of Williams Beuren's syndrome. PMID- 1913908 TI - [Early stages of angiomatosis of the retina and optic nerve disk]. AB - Based on 13 years observations of three generations of relatives with v. Hippel Lindau's disease the authors focus attention on early stages of clinically detectable retinal angiomatosis. They supplement these findings by an angioma on the optic disc in one sporadic case. They consider the ophthalmological diagnosis of priority importance for the patients and risk relatives and recommend a concept of presymptomatic screening to detect other organ sites of the disease. Early detection and treatment of lesions on eyes and other organs improves the prognosis and reduces early mortality. PMID- 1913909 TI - [Equipment for spray-freezing in ophthalmology]. AB - The authors discuss the theoretical background of the method of spray/freezing for destructive processes and their advantages. They demonstrate a cryo-apparatus IKG 3 for liquid nitrogen which is part of the Dresden equipment and was elaborated by the department for cryomedicine of the "Carl Gustav Carus" Academy in cooperation with the Technical University in Dresden. The apparatus produces a fine dispensable spray of the cooling mixture and permits treatment even of small tissue areas. PMID- 1913910 TI - [Clinical use of the spray-freezing method in ophthalmology]. AB - The authors describe a therapeutic method using spray freezing in the treatment of malignant tumours of the eyelids and conjunctivae, trichiasis and distichiasis and forms of conjunctivitis vernalis which cannot be checked by drugs. The authors discuss the results assembled in a large group of patients during 1971 1987 (4,084 patients). The results provide convincing evidence that the method is successful in these indications and that it has preference before contact freezing. Treatment of all patients was implemented using the Dresden cryotherapeutic apparatus IKG 3. PMID- 1913911 TI - [Personal experience with reconstruction of the lacrimal tract]. AB - The authors present their initial experience with the microsurgical reconstruction of lacrimatory pathways damaged by injury or inflammation. They describe complications which differ in different types of silicon cannulas used for implantation into the lacrimal canals. The achieved results indicate quite clearly the advantages of microsurgical reconstruction, in particular primary reconstruction, in case of discontinuity of the lacrimatory pathways. PMID- 1913912 TI - [Aarskog's syndrome]. AB - The authors described the rare Aarskog syndrome in a 6-year-old boy, associated with left-sided Brown's syndrome. Another 4-year-old boy came from an affected family where the brother suffered also from Aarskog's syndrome and in the mother some microsymptoms were detected. The authors recommend that patients who on examination of a refraction defect or strabism display uncommon features in the face or other parts of the body should be always subjected to a general examination incl. genetic examination. PMID- 1913913 TI - [Use of Tissucol, a tissue glue, in reconstructive surgery of large scleral defects]. AB - In a 14-year-old female patient the postoperative course of myectomy of the musculus rectus oculi externus on account of concomittant strabism was complicated by necrosis of the sclera (diameter 9 mm) at the site of intrascleral stitches and exudation into the anterior chamber and the vitreous body. For fixation of the transplant from lyophilized sclera the tissue glue Tissucol Kit was used. Tissucol rapidly and firmly joined the wound areas, its direct contact with uveal tissue did not produce an inflammatory reaction and the exudate from the anterior chamber and vitreous body was absorbed rapidly and completely. PMID- 1913914 TI - [Spectrum and dynamics of free amino acids in bovine ocular tissue and their interaction with pilocarpine. IV. The sclera]. AB - Two-dimensional ascending chromatographic analysis revealed that a 3% aqueous pilocarpine solution dropped into the conjunctival sac of cattle 2.5 hours after the last instillation shifts in a specific qualitative and quantitative way the levels of different free amino acids in the anterior, equatorial and posterior portion of the sclera. This alkaloid in the anterior and posterior part reduces and in the equatorial part of the sclera increases the total levels of free amino acids. The greatest drop in the anterior portion occurred in leucine + isoleucine methionine + valine and glutamine, in the posterior part threonine and leucine + isoleucine. The greatest rise in the equatorial part was observed in glutamine, leucine + isoleucine and taurine. PMID- 1913915 TI - [Oscillation potentials in diabetic retinopathy]. AB - The authors give an account of hitherto assembled knowledge on the mode of induction, origin and basic characteristics of oscillation potentials of the human electroretinogram. They evaluate quantitative and qualitative changes of oscillation potentials in different diseases and retinal damage, in particular diabetic retinopathies. The authors deal also with possible clinical application of the follow-up of oscillation potentials. PMID- 1913916 TI - [A.C. Celsus on cataracts]. PMID- 1913917 TI - [The heart conduction system in corrected transposition of the great vessels]. AB - Authors collected 110 cases of transposition of great arteries between 1972 and 1989. Nine transpositions were corrected and the conduction system was studied on histological serial sections in 6 of them. Two cases of corrected transposition without septal or any other defect were described in detail, one in situs solitus, another in situs inversus. According to the literature, an anterior conduction system often tends to develop in situs solitus, and posterior conduction system in situs inversus. Two presented cases as well as other cases in situs ambiguous quoted in authors' and other papers showed that an arrangement of conduction system in corrected transposition does not depend on general visceral situs but on mutual position of atrial and ventricular septa instead. PMID- 1913918 TI - [Professor Carl Sternberg and his years in Brno]. AB - The report exploiting old materials in some archives in Brno is concentrated on 14 years (from 1906 till 1920) of prof. Sternberg's life and work in Brno. The most renowned head of Brno department of pathology is introduced as a man of assiduity and indefatigable diligence according to quoted authentic documents. PMID- 1913919 TI - [Glycolipid markers in tumor cells used in immunologic and immunohistologic diagnosis of tumors. I. Factors affecting the occurrence of glycolipid tumor antigens (review)]. PMID- 1913920 TI - [Developmental trends in pathology]. AB - The paper calls attention to the main problems of pathology in Czechoslovakia. There is a need of performance standards for quality assessment and for the health insurance. PMID- 1913921 TI - [Performance standards in pathology]. AB - Author stimulates discussion about the criteria of efficiency in departments of pathology and introduces original parameters for its evaluation. He tries to contribute to defining capacity, measuring efficiency and settling objective need of pathological services. PMID- 1913922 TI - [The status of pathology in Czechoslovakia in 1988]. AB - Personnel of 112 departments of pathology and 28 autopsy stations comprises 380.74 physicians, 30.63 academic non-physicians 761.43 medical technologists, 22.04 others with secondary school qualification, 267.45 autopsy aids and 205.18 others. In 1988 they performed 40,678 autopsies (53.47 per cent rate of hospital deaths), produced 548,854 necroptic slides, 1,902,707 bioptic slides, 559,709 cytologic slides, 46,955 semi-thin sections, 75,888 histochemical and immunochemical slides (total without necroptic slides represented 82.49 per cent). One physician could be calculated as related to 106.83 autopsies and 8,226.01 slides, one medical technologist to 4,118.41 slides. The proportion of physicians to other personnel was 1 to 3.38. Data from both national republics were quoted. PMID- 1913923 TI - [The cytology laboratory of the 2d Institute of Pathology and Anatomy in Brno (present status, perspectives, problems)]. AB - The laboratory was engaged in exfoliative cytology, mainly of sputa and investigated 1450 hospitalized patients and 1410 smokers in a screening campaign during the last year. Another programme included cytology of bronchoscopical materials (2480 patients a year), fine needle aspiration cytology (550 patients), and peroperation cytology, mostly pulmonary and mammary (125 patients). A limited number of exfoliative and bronchoscopical materials could have been examined in correlation with the number of medical technologists for screening and preliminary evaluation. The laboratory shared immunochemical facilities and computerized registration of results with the others in the Institute. For future, the laboratory reckons with an increase of aspirations taken by visualization methods and with development of special technologies of material processing and evaluation. PMID- 1913924 TI - [Routine electron microscopy in the surgical pathology of tumors]. AB - The diagnostic contribution among 35 tumours from Research Institute of Clinical and Experimental Oncology Brno was 62%, 3% of all tumours were examined. The reviewed analogical data are 17-57% and 4-12%. Increased effects is reached by aimed preselection of material. About 5% of all tumours are supposed to be optimal for ultrastructural examination. Broader use of fixation in modified Millonig's solution, especially concerning consultation cases, is recommended. PMID- 1913925 TI - [Suggestions for the organization of a consultation center]. AB - Spontaneous settling of consulting centres for special fields in pathology is recommended in advance to general reform of the Czechoslovak medical services. Principles of their functioning and main tasks are outlined. PMID- 1913926 TI - [Perspectives of postgraduate education in pathology]. AB - Authors presume following changes of present status: comeback of one-step board examination, possibility of a superspecialized board examination, varied short and long-term training courses, settling of detached training centres, problems of residential training as related to payed services, need of Medical Chamber supervision. Everything will depend on new legislation. PMID- 1913927 TI - [Status and perspectives of pathology from the aspect of comparative medicine]. AB - Czechoslovak veterinary medicine developed in line with a European concept of connection of human, veterinary and plant medicine. Pathology has represented an important link of the concept which is reflected in contemporary WHO programmes concerning comparative pathology. Reformed education in veterinary pathology is prepared to contribute to human health care in this country. PMID- 1913928 TI - [The future of pathology in Czechoslovakia]. AB - Further development of Czechoslovak pathology depends on the worldwide speed and direction of progress in pathology, on economical and political progress, and on transformation of the Czechoslovak health care system. Changing orientation of pathology in advanced countries predicts an increased importance of working qualities in the whole scope of pathologist. Intrinsic factors controlling progress in pathology are varied and can be partly influenced. Participation of pathology in the new system is to be actively prepared by mutual information and cooperation. PMID- 1913929 TI - [Tumors of the peripheral sympathetic nervous system in childhood. Immunohistochemical study]. AB - Twenty tumors of the peripheral sympathetic nervous system were investigated using a spectrum of antibodies against vimentin, neurofilament triplet, S-100 protein, neuronal specific enolase (NSE), chromogranin, synaptophysin, and vasoactive intestinal polypeptide. There were two ganglioneuromas, seven stroma rich neuroblastomas (composite ganglioneuroblastomas), five undifferentiated and six differentiating stroma poor neuroblastomas (NB) included in the series. Formalin-fixed, paraffin embedded material was used. The results showed that reactivity of the antibodies was relatively high, except the reactivity against synaptophysin. The tumor cell population showed a heterogeneous positivity in all cases. Only some undifferentiated NB were positive with the employed antibodies, which reduces the diagnostic benefit in a group of NB in which diagnostic demands of the immunohistochemistry are most important. The best results in undifferentiated NB were obtained with polyclonal antibody against NSE. This antibody is, however, not specific. Positive results of the immunohistochemistry in this group of tumors should be evaluated with caution. PMID- 1913930 TI - AIDS in Canada. PMID- 1913931 TI - Preliminary analysis: HIV serosurvey of orthopedic surgeons, 1991. PMID- 1913932 TI - Salmonella isolations associated with reptiles--Alberta. PMID- 1913933 TI - Tropical health and quarantine notes. PMID- 1913934 TI - Adverse events temporally associated with immunizing agents--1989 report. PMID- 1913935 TI - National Advisory Committee on Immunization (NACI) statement on universal immunization against hepatitis B. PMID- 1913936 TI - [Reliability of the psychiatric section in the 10th revision of the International Classification of Diseases]. AB - In collaboration with WHO the authors participated in sessions on the reliability of the Vth chapter of mental disease of the 10th revision of the International Classification of Diseases. The object was to evaluate the comprehensibility and utility of the diagnosis of mental disorders, evaluate to what extent the new classification describes adequately disorders of different types of psychiatric patients and to provide information on the extent and type of diagnostic agreement and disagreement. The evaluation was done by four psychiatrists; a total of 38 written case-histories were evaluated (30 patients of the Psychiatric Research Institute and 8 case-histories from other centres). Diagnostic agreement according to Kappa was very good, best in organic mental disorders and schizophrenic disorders, approximately equal in affective and neurotic disorders. It was lowest in personality disorders. The investigation indicates diagnostic agreement practically equal to that in ICD-9. More reliable data will be obtained after summarization of the entire WHO investigation which was implemented in various departments in the world. PMID- 1913937 TI - [Irrationality in psychiatry. I. Irrationality in analytical psychology]. AB - In the author's opinion the contemporary western world is experiencing an offensive of irrationality which affects also psychiatry. When psychiatry got rid of irrational illusions of preceding centuries, analytical psychology contributed to the introduction of irrationality into psychiatry. In the first part of his paper he maintains that Freud's share was not substantial in this respect and that in particular Jung contributed towards the development of irrational trends in psychiatry by this concept of collective unconscious. In the second part of his paper the author deals with so-called transpersonal, psychology, in particular the contribution made by the Czech psychiatrist Grof who, based on his experiments with LSD, created the theory of three levels of experience from unconscious (psychodynamic, perinatal, and transpersonal). His interpretation is a relapse of neoplatonism and represents antirational agnostic spiritualism with utopic antipsychiatric elements. In the third part of his paper the author deals with Capro's ideology of the New Age Movement to the establishment of which Ghof contributed in an important way. The New Age ideology is an irrational conglomeration of anti-civilization trends which negate modern thinking. The chances of manking are fallaciously seen in alienation from science and an approach to mysticism and irrational Asian traditions. Contemporary popularity of irrational trends, incl. transpersonal psychology, is a reaction of the overationalized society. Consequential enforcement of transpersonal psychology would imply a negation of the entire arsenal of thinking in psychiatry as a medial discipline. PMID- 1913938 TI - [Irrationality in psychiatry. II. Transpersonal psychology]. PMID- 1913939 TI - [Irrationality in psychiatry. III. New age]. PMID- 1913940 TI - [Catamnesis of a group of 84 castrated sexual offenders]. AB - The authors examined 84 castrated sexual delinquents after a 1-15-year interval following castration. 18% of the subjects were capable of occasional sexual intercourse. 21% of the subjects lived in a stable heterosexual partnership. Almost half the men had occasional erections in the morning. More than one third of the group masturbates occasionally. Only three men committed another sexual offence after castration. These offences did not have an aggressive character. From a sub-group of 32 men punished previously on account of non-sexual offences 15, i.e. almost half of them, committed further non-sexual offences. One quarter of the examined subjects had objections to the results of castration. Most frequently because sex was lacking in their life. The authors did not observe serious physical or mental consequences of castration in the examined men. Castration must be considered even nowadays an important part of the therapeutic arsenal in sexual delinquents. It should be performed in those patients who cannot be influenced by other types of treatment. PMID- 1913941 TI - [Evaluation of the clinical typing of patients in psychotherapeutic practice]. AB - The authors describe the clinical typology of patients which develops spontaneously in a psychotherapeutic department. Different categories are investigated in association with other characteristics such as the functioning of the patient's original family, his position among siblings, profession, acquaintances. The typology is also compared with some characteristics of the course and results of treatment. In large groups statistical data are illustrated by brief case--histories. The revealed relationships between variables provide evidence of the "logic" of spontaneously developed typology; justification and restrictions of clinical labeling. PMID- 1913942 TI - [Alcoholic epilepsy]. AB - The author analyzes a group of 83 patients with epileptic fits which developed in conjunction with drinking. She compares them with a group investigated 12 years previously. She mentions also some catamnestic findings pertaining to the group. The author describes signs of alcoholic epilepsy which include age above 30 years, in particular a 10-year history of drinking, altered reactivity of the brain to alcohol, high alcohol tolerance, development of fits without an aura and how frequency of fits. The author reflects on the causes of alcoholic epilepsy and emphasizes the basic therapy--strict abstinence. She proved also an increase of somatic and neurological damage and the number of deaths in subjects with the diagnosis of alcoholic epilepsy. PMID- 1913943 TI - [Disorders of sexual function in men after strokes]. AB - The author examined 74 men in the rehabilitation stage after a cerebrovascular attack. A cerebrovascular attack can influence sexual function in younger and middle-aged men. Transient sexual complaints, in particular in younger patients after a cerebrovascular attack were favourably influenced by psychotherapy (standardized talk with the patient, possibly his wife). Difficulties may have also a pharmacological cause, in particular during prolonged treatment with methyldopa combined with beta--blockers. Change of this treatment contributed to normalization on improvement of sexuality in practically all 40-49 year-old patients and almost half 50-59 year-old patients. Little therapeutic success was achieved hemiparetic patients with concurrent aphasia. PMID- 1913944 TI - [Ethical aspects in the diagnosis of hysteria]. AB - The diagnosis of hysteria underwent historical development. The definition of the diagnosis by our classics and the contemporary definition lack continuity. The classics defined it accurately and were able to describe actual symptoms, their categories, links, and were able to differentiate subtly between different forms. In the contemporary medical documentation the description is vague. The entries in health records have sometimes so many gaps that it is sometimes impossible to find out on which symptoms or manifestations the diagnosis was based. This makes us think of intuitive, empathic or short-cut approaches. It is obvious that the diagnosis of hysteria has for different reasons new contents with the possible implications: formerly diagnosis, nowadays insult. One of the ways how to resolve this controversy is to use more general formulations such as they are in DSM III or in the ICD 10 which is being prepared, which abondon the contamined terminology and introduce more general precisely defined terms. PMID- 1913945 TI - [Balneophysiatry in psychiatry from the aspect of the autonomic nervous system and differential psychophysiology]. PMID- 1913946 TI - [Biological and experimental markers of sexual aggression]. AB - Forty men who committed sexual offences with a varying extent of aggressiveness were examined by a series of psychological tests, phalloplethysmography and electroencephalography. The plasma testosterone level was assessed and in indicated cases the karyotype. Frequently in the delinquents an abnormal course of psychosexual development was revealed, disorders of sex life, the presence of sexual deviations and atypical EEG findings. The extent of aggression of the offence correlated significantly with younger age of the delinquent and the result of the phalloplethysomographic examination. Prediction of future aggressive behaviour of a subject is difficult even when modern examination methods are used. PMID- 1913947 TI - [What is next in the development of antidepressives?]. AB - After some findings concerning the mode of action of antidepressants, it was possible to hypothesize the molecular basis of depressive disorders (monoamine hypothesis, receptor hypothesis). These informations made the preparation of drugs acting by a completely new mechanism. Possible an antidepressant effect was observed after the administration of GABA-ergic agonists, or agents influencing dopaminergic transmission, S-adenosylmethionine, and drugs influencing second messenger systems. As a consequence of these findings, the GABA-ergic hypothesis, hypothesis of endogenous ligand (barinine hypothesis is discussed in more detail), and second messenger hypothesis of affective disorders were formulated. Agents influencing second messenger systems and S-adenosylmethionine seem to be a promising field of future investigation. PMID- 1913948 TI - [Psychoanalytic theory of personality and its use in practice. III]. AB - In the first part of the paper the author described the most important psychoanalytical theories and models of mind, in the second part she attempted their synthesis and outline of the hierarchical model of the psychic apparatus. In the last part she deals with the possibilities to apply the psychoanalytical theory in the diagnostic and therapeutic process. With different modes of the personality pattern according to the hierarchical model correspond different areas of psycho pathology and appropriate optimal therapeutic approaches. In the conclusion the considerations of the psychiatrist concerned with the theory of psychoanalysis are presented in a narrative form. PMID- 1913949 TI - [Overcoming resistance to lithium prophylaxis]. AB - At least 30% of maniodepressive patients are resistant to the prophyloctic administration of lithium, i. e. the course of the disease is not affected at all or only to a minimal extent. The investigation tested the effect by adding carbamazepine to the hitherto ineffective administration of lithium in 20 maniodepressive patients with the bipolar form. The open study was arranged in a mirror-image fashion; two two-year periods were compared: administration of lithium alone with administration of lithium and carbamazepine. Lithium carbonate was administered, 600-1500 mg/day with serum levels of 0.45-0.95 mval/l and carbamazepine 200-1200 mg/day. When the above combination was administered, a substantial reduction of the number of both phases occurred as well as a reduction of hospital admissions. The combination of lithium and carbamazepine substantially improved the course in 80% of patients hitherto resistant to lithium: 35% of the patients had no further manifestations of the disease, 45% had a lower frequency, intensity and duration of the phases. In 20% of the patients the disease developed with unaltered intensity, PMID- 1913950 TI - [Behavior of the aged in a hospital environment. Case reports]. AB - The author deals with the problem of adaptation of old people after admission to hospital, draws attention to the necessity of suitable preparation, a tactful, empathic approach in dealing with old people. On selected case-histories the most frequent difficulties are demonstrated--ament conditions, depressive syndrome and attempts to find an optimal preparation before hospitalisation of old people. At the same time attention is drawn to the most frequent mistakes which are made during an inconsiderate transfer and their sequelae. PMID- 1913951 TI - [Psychological disorders in Ethiopian university students--problems in transcultural psychiatry]. AB - In the course of the ten-year period 1979-1988 the authors subjected to psychiatric examination or hospitalized 52 Ethiopian university students. The authors were concerned with the problem whether in the development and character of the psychopathological symptoms factors of the different cultural environment participated. University students sent to Czechoslovakia are a specific group which is not representative of the Ethiopian population. This may be the reason why the revealed symptoms did not differ markedly from conditions in the local population. This applies in particular to neurotic disorders, among which the neurasthenic syndrome predominated. In 14 hospitalized students schizophrenia was diagnosed 6 times, endogenous depression 6 times and neurotic symptoms due to maladaptation twice. The schizophrenic attacks presented classical symptoms, after their regression there was however, complete remission and thus the original diagnosis was somewhat doubtful. PMID- 1913952 TI - [Organization of self-help groups for patients with psychogenic eating disorders]. AB - The author pays attention to the organization of self-help groups of women suffering from anorexia nervosa and bulimia and illustrates them on several examples of self-help groups in the USA, Austria and Czechoslovakia. Great attention is paid to the BASH programme (Bulimia Anorexia Self-help) in St. Louis in the USA, one of the first self-help groups developing within the framework of a therapeutic and research institution for patients with psychogenic eating disorders. In the conclusion of the review the author presents his own experience with the organization of a MAB (mental anorexia--bulimia club) founded in 1989 at the Psychiatric Clinic of the Faculty of General Medicine, Charles University in Prague, attached to the Unit of specialized care of patients with psychogenic eating disorders. He emphasizes the necessity of differentiated and long-term therapeutic action on patients with psychogenic eating disorders where self-help groups hold an irreplaceable place. Attention is drawn to the fact that in addition to detection, emotional and social rehabilitation in the treatment of patients with preclinical symptoms a very important place is held by self-help groups which have a specific therapeutic influence and importance. PMID- 1913953 TI - [Maintenance therapy in schizophrenia using clozapine]. AB - Most of the experience with the atypical neuroleptic of Clozapine (Leponex, Sandoz) pertains to active treatment. In conjunction with possible risks, at present its administration in selected groups of patients is recommended. The authors describe the results of an intraindividual comparison of Clozapine in 11 patients with the diagnosis of schizophrenia (according to ICD-9), 7 men, mean age 30.5 years with previous neuroleptic treatment. The average period for comparison was 2.3 years (1.5-4 years), the mean daily dose of Clozapine was 200 mg (50-400 mg). During Clozapine treatment the hospitalization period was significantly shorter and the number of hospital admissions was lower. The frequency of undesirable effects was equal during both periods. During Clozapine treatment morning sleepiness and hypersalivation were more frequent and during treatment with neuroleptics extrapyramidal undesirable effects. In none of the patients they caused discontinuation of treatment. Transient leukopenia after Clozapine in one patient was improved after reduction of the dose. The paper is supplemented by the case-history of female patient treated by Clozapine monotherapy during 17 years. PMID- 1913954 TI - [From whence psychiatry? (contribution of the gentle revolution)]. AB - Every ideology--when it has absolute rule in society--tries to proclaim its infallibility and to eliminate even mere indications of competition by all possible means of its power. This has a very deleterious effect on the thinking of people, on the overall development of human personality. This deformation has also a negative impact on the psychotherapeutic relation example: in addition to depriving the psychotherapeutic repertoire, in certain situations it may have a iatrogenic effect on the patient. PMID- 1913955 TI - [Relation of intra-acinar arteries and their regression with changes of pulmonary artery pressure and blood gas values]. AB - Pulmonary hypertension (PAH) induced by monocrotaline in thirteen rhesus monkeys, seven of them treated by hydralazine to reduce PAH. In hypertensive animals the PAP and PaCO2 increased, the PaO2 decreased. The structural changes in intra acinar artery manifested mainly by an increase in number of muscular artery resulting from muscularization of precursor cells (pericytes and intermediate cells) located within partially muscular and nonmuscular arterial wall to smooth muscle cell, and by the medial wall thickened due to hypertrophy and hyperplasia of smooth muscle cells as well as accumulation of a large amount of collagen, especially the type 1 collagen. In treated animals the PAPm dropped concomitantly with blood gas values reversing to normal level. The remodelled arteries showed clearly structural regressions: The medial wall thickness was decreased in which the hypertrophied smooth muscles became slender or disappeared, the amount of extracellular matrix, especially the volume density of collagen, decreased. Most of muscularized arteries reversed to nonmuscular arteries leading to an increase in number of nonmuscular artery and a decrease in number of muscular artery. It is concluded that the intra-acinar artery remodelling and their regression closely correlated with the changes of PAP and blood gas values. PMID- 1913956 TI - [Change in pulmonary artery and aorta reactions of isobaric hypoxic pulmonary hypertension in guinea-pig and milrinone's effect]. AB - The pulmonary hypertensive model was built on guinea-pig after 1 week of isobaric hypoxia. Meanwhile, the response of pulmonary artery ring (PAR) to noradrenaline (NA) increased significantly as compared with control, but it returned to normal level after 2 week of hypoxia. The similar change was not found in aorta ring (AR). The cumulative concentration response curves of PAR, AR to NA shifted to right with dose dependent relationship after Mil pretreated either control or hypoxic groups. Hypoxia decreased the sensitivity of AR to Mil significantly but not much on PAR. PMID- 1913957 TI - [Experimental study on evaluation of pulmonary hypertension by Doppler echocardiography]. AB - The purpose of this study was to evaluate the influence of pulmonary blood flow, pulmonary vascular resistance and myocardial contractivity on several Doppler predictors of pulmonary hypertension. Acute experimental study on 14 open-chest dogs was performed. Pulmonary artery pressure, pulmonary blood flow volume and pulmonary Doppler flow velocity spectrum were recorded under different pathophysiologic states. The results showed that pulmonary hypertension could be predicted by Doppler echocardiography. Different regression equations ought to be adopted in assessing pulmonary hypertension of different pathophysiologic types. PMID- 1913958 TI - [The observation of experimental respiratory distress syndrome and effects of anisodamine]. AB - The respiratory distress syndrome (RDS) model induced by oleic acid injection in dogs and treated by anisodamine were observed. The clinical picture, blood gas parameters, Pap, Pwp, blood cells count, hemocoagulogram, CH50, and surface tension of BALF were studied in order to determine the pathophysiological mechanism and effects of anisodamine. According to the studies in our laboratory, it was suggested that the complement activation and neutrophil aggregation induced by C5a and mediators released by it and other way are likely to be the initiation factors. The lung injuries complicated diffuse intravascular coagulation with fibrinolysis occurred for whole 72 hours period. The anisodamine seems to exert certain therapeutic effects on RDS through preventing the complement activation and enable the lysosomal elimination decrease and stimulate the II-type epithelia to be repaired. PMID- 1913959 TI - [The observation of changes in plasma PGI2 and TXA2 levels and the therapeutic effect of tetramethylpyrazine in E. coli induced acute lung injury in rabbits]. AB - Thirty two rabbits were equally divided at random into 4 groups: A. control; B. E.coli; C. E.coli + ibuprofen; D. E.coli + tetramethylpyrazine. The plasma concentration of 6-keto-PGF1 alpha and TXB2, arterial blood gas as well as platelet aggregability were measured and the pathological changes of lung tissue were observed. The results suggest that TXA2 and PGI2 do take part in the pathogenesis of acute lung injury; that PGI2 may serve as an indicator in the evaluation of the degree of injury in the pulmonary endothelial cells and may also contribute to septic shock; and that both tetramethylpyrazine and ibuprofen possess therapeutic effects on the amelioration of acute lung injury, and the former is rather stronger than the latter in the inhibitory effect on granulocytic sequestration within the lung. PMID- 1913960 TI - [Effects of nifedipine on pulmonary hypertension in patients with chronic obstructive pulmonary diseases--a comparison with oxygen administration]. AB - We evaluated the effects of the calcium channel blocker nifedipine (Nf) as a vasodilator compared with oxygen administration on pulmonary hypertension and right ventricular performance in 15 patients with COPD. 1. Compared with baseline, sublingual administration of Nf (average dose 39.3mg) decreased mean pulmonary artery pressure (mPAP) and total pulmonary vascular resistance (TPVR) significantly. Cardiac index (CI) and oxygen transport were increased. PaO2 were unchanged and PvO2 were slightly increased after administration of Nf. 2. Compared with oxygen administration, Nf caused significant fall of TPVR. CI and oxygen transport increased. 3. In eleven of 15 patients, continued hourly Nf doses (from 20 to 60mg) produced a significant reduction in mPAP and TPVR. All patients but one did not produce symptomatic systemic hypotension. We considered that higher dose (30mg) of Nf was required to produce marked hemodynamic response in patients with COPD without any side effect. PMID- 1913961 TI - [Airway challenge test with propranolol]. AB - We investigated airway response to propranolol in 48 asthmatics, 17 subjects with chronic bronchitis and 19 normal subjects. The positive rate for propranolol challenge was 93.8% in asthma group, 5.9% in chronic bronchitis group while none in normal group had positive response. The challenge was highly reproducible, and it had few side-effects. This indicated that the challenge was specific and sensitive in diagnosis of asthma, it was a safe, reliable method of measuring non specific airway responsiveness. Furthermore we also demonstrated that PC20 for propranolol did not relate to PC20 for methacholine, and that the calibre of airway did not significantly influence the airway response to propranolol. PMID- 1913962 TI - [Airway provocation test with ragweed pollenosis and late-phase reaction]. AB - Ragweed pollen extract inhalation airway provocation test (APT) were studied in 55 patients with ragweed pollenosis. Single dosage of 9000 PNU ragweed extract was applied and positive response was defined as more than 35% fall in SGrs at the dose of PT35-Grs. Among 55 patients, positive APT was found in 27 case (49%), dual late-pase responses in 11 patients, single late-phase response only was found 2 patients in complicated asthma group. Late-phase response were well related to the increased specific IgE, and strong positive skin test response (wheal greater than 11 mm). The results suggested ragweed pollen was one of the important allergen causing bronchial asthma. There was airway hyperresponsiveness to ragweed pollen in some patients (20%) with ragweed pollenosis without asthmatic symptoms. PMID- 1913963 TI - [Application of positive end expiratory pressure (PEEP) and continuous positive airway pressure (CPAP) in the treatment of asthma]. AB - Two intubated young adults with respiratory failure and acidosis due to severe asthma attack were treated by mechanical ventilation with PEEP. Two hours after using of PEEP the expiratory resistance decreased from 35 to 14 cmH2O/L/Sec and 56 to 18 cmH2O/L/Sec respectively, and within two days they were successfully weaned from mechanical ventilation. Another fifteen patients with moderate asthmatic attack were treated with CPAP via a mask from Siemens 900C ventilator. Twenty minutes later the FEV1 and VC were significantly increased from 1.19 +/- 0.69 L to 1.36 +/- 0.73 L and 2.41 +/- 0.97 to 2.65 +/- 0.94 L respectively. We concluded that, PEEP and CPAP have mechanical bronchodilative effect on spasm bronchi, and could be used as a effective way to treat severe asthma attack. PMID- 1913964 TI - [Measurements of P-V curves of the lungs and its use in clinical assessment]. AB - Pressure-volume curves of the lungs in 112 healthy nonsmokers and 39 patients with obstructive emphysema or pulmonary interstitial diseases were studied. Normal values by decade/sex groups and regression formulas for dynamic compliance at 20 breath/min (CLdyn20), statis lung compliance (CLst) and maximal static lung recoil pressure (Pst(L)max) against age, height, weight, and body surface area were calculated. Various factors affecting the lung compliance we studied. Our studies confirmed the high CLst, loss of Pst(L)max in patients with obstructive pulmonary emphysema, and also showed that there are reduction of CLst and increase of Pst(L)max in patients with pulmonary interstitial diseases. PMID- 1913965 TI - [Lymphomatoid granulomatosis. A report of 2 cases]. AB - Two patients with lymphomatoid granulomatosis were diagnosed by postmortem autopsy or exploratory thoracotomy. The lung, skin, spleen, renal and lymph nodes were involved. The most common presenting complaints are fever, cough, expectoration shortness of breath. The radiographic manifestations are multiple, bilateral nodular shadows. The histologic features is a unique form of pulmonary angiitis and granulomatosis, which is a necrotizing angiocentric and angio destructive infiltrative process composed of small lymphocytes and atypical lymphoreticular cells. PMID- 1913966 TI - [Surgical treatment of adenosquamous carcinoma of the lung--analysis of 223 cases]. AB - The curative effect of 223 cases of primary pulmonary adenosquamous carcinoma. The adenosquamous carcinoma made up 10.8 percent of the total primary lung cancer in the same therapeutic period. We reexamined the specimen which had been excised in operation about 187 cases under the optic microscope and found out the amount of squamous cell is more than adenocarcinoma. The ratio is about 56.7 and 34.8 percent respectively. But the curative effect of adenosquamous carcinoma not only was worse than that of the squamous carcinoma, but also the adenocarcinoma and small cell lung cancer. So it reminds us the adenosquamous carcinoma has it's specific biologic characteristics. The operation is the most important way in curing adenosquamous carcinoma. The stage I and II should be operated early, and for stage III, we must follow the indication strictly. We select the comprehensive method in stage IIIb, such as radiotherapy or chemical therapy to raise the existent rate. PMID- 1913967 TI - [The determination and evaluation of the plasma amino acid in respiratory failure]. AB - The measurement of the plasma amino acid was made in 15 patients with chronic respiratory failure and 15 persons of control. The results showed: (1) The plasma acid model changed. Lysine increases and arginine decreases, due to hypothermia. Hypercapnia imbalance of acid and alkali and changes of hepatic dysfunction etc. (2) The prognosis of respiratory failure as well as its severity was judged according to the decreasing extent of arginine and BCAA. The more worse the condition of the disease, the more lowering of the level of arginine and BCAA. (3) The changes of blood gas analysis and hepatic dysfunction may effect on the metabolism of plasma amino acid in some degree. (4) Hypoxemia in infected patients with respiratory failure may cause peripheral deficit of energy. We suggested that patients should be given BCAA and arginine for more energy as anti infection and oxygen therapy were used. PMID- 1913968 TI - [Determination of zinc, copper, iron and zinc/copper ratio in the hair of active pulmonary tuberculosis patients]. AB - The determination of zinc (Zn), copper (Cu), iron (Fe) and zinc/copper ratio (Zn/Cu) in hair in 70 active pulmonary tuberculosis and 51 healthy individuals were reported. The Zn and Zn/Cu in hair of patients with pulmonary tuberculosis, in cases with cavities or noncavities and in cases with smear positive or negative sputum were lower than that of healthy individuals (P less than 0.01). But there was no difference in the hair Fe between the patients and healthy individuals. PMID- 1913969 TI - [Study on BCG vaccination and incidence of children's tuberculous meningitis in Liaoning province]. AB - The purpose of this study was to assess the effect of BCG vaccination on the incidence of tuberculous meningitis in children. A retrospective review was undertaken to find out vaccination rate of BCG and positive conversion mantoux rate in newborn infants. The results obtained were as follow: in 1980, vaccination rate was 51.61%, and the positive conversion Mantoux rate was 87.86%; in 1988 vaccination rate was 96.06%, and the positive conversion Mantoux rate was 94.92%. With the increase vaccination rate of BCG the incidence of tuberculous meningitis in children have decreased: in 1980 it was 3.27/100000; in 1988 it was 0.95/100000. The annual average incidence rate decreased by 14.28%. PMID- 1913970 TI - [Advances in the research on DNA probes for Mycobacterium]. PMID- 1913971 TI - [Chemotherapy of extrapulmonary tuberculosis]. PMID- 1913972 TI - Bioactivation of xenobiotics by prostaglandin H synthase. AB - Prostaglandin H synthase (PHS) catalyzes the oxidation of arachidonic acid to prostaglandin H2 in reactions which utilize two activities, a cyclooxygenase and a peroxidase. These enzymatic activities generate enzyme- and substrate-derived free radical intermediates which can oxidize xenobiotics to biologically reactive intermediates. As a consequence, in the presence of arachidonic acid or a peroxide source, PHS can bioactivate many chemical carcinogens to their ultimate mutagenic and carcinogenic forms. In general, PHS-dependent bioactivation is most important in extrahepatic tissues with low monooxygenase activity such as the urinary bladder, renal medulla, skin and lung. Mutagenicity assays are useful in the detection of compounds which are converted to genotoxic metabolites during PHS oxidation. In addition, the oxidation of xenobiotics by PHS often form metabolites or adducts to cellular macromolecules which are specific for peroxidase- or peroxyl radical-dependent reactions. These specific metabolites and/or adducts have served as biological markers of xenobiotic bioactivation by PHS in certain tissues. Evidence is presented which supports a role for PHS in the bioactivation of several polycyclic aromatic hydrocarbons and aromatic amines, two classes of carcinogens which induce extrahepatic neoplasia. It should be emphasized that the toxicities induced by PHS-dependent bioactivation of xenobiotics are not limited to carcinogenicity. Examples are given which demonstrate a role for PHS in pulmonary toxicity, teratogenicity, nephrotoxicity and myelotoxicity. PMID- 1913973 TI - DNA sequence recognition by the antitumor antibiotic CC-1065 and analogs of CC 1065. AB - The DNA base pair preferences of the antitumor antibiotic CC-1065 and two analogs of CC-1065 were studied by following the rate of covalent bond formation (N-3 adenine adduct) with DNA oligomers containing the 5'NNTTA* and 5'NNAAA* sequences (N = nucleotide, A* = alkylated adenine). The rate of adduct formation of CC-1065 is greatly affected by DNA base changes at the fourth and fifth positions of the bonding site for the 5'NNAAA sequences, but not the 5'NNTTA sequences. However, an analog of CC-1065 containing the same alkylating moiety as CC-1065, but not the third fused ring system or additional methylene and oxygen substituents, shows similar rates of adduct formation for all sequences. A second analog of CC 1065 containing three fused ring systems, but not the methylene and oxygen substituents of CC-1065, shows rates of adduct formation with the same sequence dependence as CC-1065, but does not distinguish between the sequences to the degree shown by CC-1065. Adduct formation of CC-1065, but not the analogs, competes with a reversibly bound species. Thymine bases to the 3' side of a potentially reactive adenine or a cytosine base at the fifth position from the bonding adenine create reversible binding sites which decrease the rate of adduct formation of CC-1065. The sequence 5'GCGAATT binds CC-1065 only reversibly. This sequence can compete for CC-1065 with covalent bonding sequences if the sites are located in different oligomers, or if the sites are located (overlapped or not overlapped) in the same oligomer. The results of these competitive binding experiments suggest that the transfer of CC-1065 from the reversible binding site to the covalent bonding site with both sites located on a single DNA duplex, not overlapped, occurs through an equilibrium of CC-1065 in solution, not by migration of CC-1065 in the minor groove. PMID- 1913974 TI - Regiospecific oxidation of polycyclic aromatic dihydrodiols by rat liver dihydrodiol dehydrogenase. AB - Rat liver dihydrodiol dehydrogenase (DDH, E.C. 1.3.1.20) has recently been shown to oxidize the highly carcinogenic benz[a]anthracene-3,4- dihydrodiol in an NADP(+)-dependent reaction to its corresponding catechol. The present study is a systematic investigation of the substrate specificity of the purified enzyme towards synthetic trans-dihydrodiol metabolites of phenanthrene, benz[a]anthracene, chrysene, dibenz[a, h]anthracene and benzo[a]pyrene. DDH exhibited a remarkable regiospecificity of enzymatic catalysis with regard to the site of the dihydrodiol moiety of the parent hydrocarbon. M-region- and, with lower efficiency, bay-region dihydrodiols were found to be good substrates of the enzyme with maximal velocities between 20-80 nmol/min per mg enzyme and Km values in the micromolar range. K-region dihydrodiols were not accepted as substrates. Dihydrodiols situated at the terminal ring of an anthracene-type structure such as benz[a]anthracene-8,9-dihydrodiol as well as the corresponding dihydrodiol epoxides were also not oxidized by DDH at measurable rates. The results provide evidence for a detoxifying role of DDH in the metabolism of the chemical carcinogens benz[a]anthracene, chrysene and dibenz[a, h]anthracene. PMID- 1913975 TI - Southern flounder hepatic and intestinal metabolism and DNA binding of benzo[a]pyrene (BaP) metabolites following dietary administration of low doses of BaP, BaP-7,8-dihydrodiol or a BaP metabolite mixture. AB - Certain finfish species living in chemically polluted environments exhibit a high incidence of gastrointestinal tract tumors. Carnivorous fish in such environments are likely to consume invertebrates which contain chemical procarcinogens and the invertebrate biotransformation products of these compounds. The retention in tissues, extent of DNA adduct formation in liver and intestine, and metabolite composition of bile was investigated in southern flounder following gavage with pure [3H]- or [14C]benzo[a]pyrene (BaP), pure [14C]benzo[a]pyrene-7,8-dihydrodiol (BaP-7,8D), or hepatopancreas from spiny lobsters previously dosed with [3H]- or [14C]BaP (Metab.HP). Metab.HP contained mainly polar conjugates of BaP diols, triols and tetraols. BaP-7,8D was retained in fish tissues and bile at 24 h to a greater extent (33.6% of the dose), than either BaP (19.00%) or Metab.HP (6.6%). Hepatic and intestinal DNA isolated from all dosed fish contained covalently bound radioactivity, but exposure to BaP-7,8D or BaP resulted in significantly higher binding in both tissues than exposure to Metab.HP. Hepatic DNA from BaP and BaP-7,8D-dosed flounder contained 0.24 +/- 0.07 and 0.33 +/- 0.06 pmol BaP equivalents/mg DNA respectively (mean +/- S.E.), while hepatic DNA isolated from Metab.HP-dosed flounder contained 0.006 +/- 0.002 pmol BaP equivalents/mg DNA. Binding of radioactivity to intestinal DNA was significantly higher than to hepatic DNA for flounder dosed with Metab.HP (0.026 +/- 0.003) or with BaP (0.76 +/- 0.27) but not for flounder dosed with BaP-7,8D (0.44 +/- 0.09). These studies show that dietary BaP, and metabolites likely to be present in invertebrates, can be absorbed by the southern flounder and form DNA adducts in target organs. PMID- 1913976 TI - Mechanisms of nickel carcinogenesis. Interaction of Ni(II) with 2' deoxynucleosides and 2'-deoxynucleotides. AB - Interactions of Ni(II) with the base moieties of 2'-deoxynucleosides and 2' deoxynucleotides were studied by means of UV difference spectroscopy in order to elucidate the mechanisms of site-specific enhancement by Ni(II) of DNA base oxidation with active oxygen species, observed previously (Kasprzak et al., Cancer Res., 49 (1989) 5964; Carcinogenesis, 11 (1990) 647). The interactions were generally weak and could be quantitated only at pH 7.2-7.9. The resulting coordination binding of Ni(II) was stronger with the purine derivatives, especially these of guanine, than with pyrimidine derivatives. Also, Ni(II) interacted more strongly with the bases of 2'-deoxynucleotides than with the bases of 2'-deoxynucleosides. The apparent stability constants for the interactions calculated with the use of a non-linear regression method, equalled 102 +/- 14, 159 +/- 30 and 290 +/- 70 M-1 for Ni(II) coordinated by 5'dAMP, 5'dADP and 5'dATP, respectively, and 305 +/- 73, 191 +/- 54, and 270 +/- 28 M-1 for 5'dGMP, 5'dGDP and 5'dGTP, respectively. Stability constant for the dG Ni(II) interaction was 39 +/- 7 M-1. Interactions of Ni(II) with the bases of dA, dC, dT and the dC- and dT- mono-, di- and tri-phosphates were too weak for meaningful quantitation. The strongest relative Ni(II) interaction with dG may explain high sensitivity of the dG site at the DNA molecule to Ni(II)-mediated oxidation observed in vitro and in vivo. The present results contrast with Ni(II)-directed site specific cleavage of DNA with H2O2 that occurs preferentially at the pyrimidine bases (Kawanishi et al., Carcinogenesis, 10 (1989) 2231). PMID- 1913977 TI - Molecular mechanisms of quinone cytotoxicity. AB - Quinones are probably found in all respiring animal and plant cells. They are widely used as anticancer, antibacterial or antimalarial drugs and as fungicides. Toxicity can arise as a result of their use as well as by the metabolism of other drugs and various environmental toxins or dietary constituents. In rapidly dividing cells such as tumor cells, cytotoxicity has been attributed to DNA modification. However the molecular basis for the initiation of quinone cytotoxicity in resting or non-dividing cells has been attributed to the alkylation of essential protein thiol or amine groups and/or the oxidation of essential protein thiols by activated oxygen species and/or GSSG. Oxidative stress arises when the quinone is reduced by reductases to a semiquinone radical which reduces oxygen to superoxide radicals and reforms the quinone. This futile redox cycling and oxygen activation forms cytotoxic levels of hydrogen peroxide and GSSG is retained by the cell and causes cytotoxic mixed protein disulfide formation. Most quinones form GSH conjugates which also undergo futile redox cycling and oxygen activation. Prior depletion of cell GSH markedly increases the cell's susceptibility to alkylating quinones but can protect the cell against certain redox cycling quinones. Cytotoxicity induced by hydroquinones in isolated hepatocytes can be attributed to quinones formed by autoxidation. The higher redox potential benzoquinones and naphthoquinones are the most cytotoxic presumably because of their higher electrophilicty and thiol reactivity and/or because the quinones or GSH conjugates are more readily reduced to semiquinones which activate oxygen. PMID- 1913978 TI - Cell-cycle specific cytotoxicity mediated by stizophyllin (2 alpha,3 beta,12 beta trihydroxypregna-4,7,16-trien-20-one), a novel electrophilic pregnane isolated from Stizophyllum riparium. AB - A structurally-novel pregnane derivative, 2 alpha,3 beta,12 beta-trihydroxypregna 4,7,16-trien-20-one (stizophyllin), was isolated from an extract of Stizophyllum riparium (H.B.K.) Sandw. on the basis of bioactivity-guided fractionation and confirmed to mediate a potent cytotoxic response with cultured P-388 cells. We presently report a detailed isolation procedure and the results of studies designed to examine its mechanism of action. By means of a Michael-type addition, stizophyllin formed adducts with nucleophilic substances such as L-cysteine and beta-mercaptoethanol. The adduct with beta-mercaptoethanol was isolated, structurally characterized, and found to be 20-fold less cytotoxic than stizophyllin. Stizophyllin interacted with DNA, but no mutagenicity was observed with Salmonella typhimurium strain TM677 or cultured Chinese hamster ovary cells, and no in vitro reaction occurred with guanosine. Relative to control cell cultures, the total biosynthesis of DNA, RNA or protein was reduced when P-388 cells were treated with stizophyllin. However, the cell number did not increase in the presence of inhibitory stizophyllin concentrations (e.g., 4 micrograms/ml), and the DNA content (per cell) actually doubled after approximately 48 h. Consistent with this, stizophyllin blocked the cells in the G2 + M compartment of the cycle, and the block appeared to be specific for the G2 phase. Accordingly, stizophyllin did not modulate in vitro tubulin polymerization reactions nor did it affect the morphology of dibutyryl cAMP-treated astrocytoma cells in culture. These data suggest that the cytotoxic activity of stizophyllin is mediated by covalent reaction with a cellular component (such as a sulfhydryl containing protein) by means of a Michael-type addition. Based on the cell-cycle specificity of the response, it appears that this interaction prevents the cells from progressing through mitosis. PMID- 1913979 TI - Genotoxicity of 1,3-dichloro-2-propanol in the SOS chromotest and in the Ames test. Elucidation of the genotoxic mechanism. AB - 1,3-Dichloro-2-propanol (1,3-DCP-OH, glycerol dichlorohydrin) is of great importance in many industrial processes and has been detected in foodstuffs, in particular in soup spices and instant soups. It has been shown to be carcinogenic, genotoxic and mutagenic. Its genotoxic mechanisms are, however, not yet entirely understood. We have investigated whether alcohol dehydrogenase (ADH) catalysed activation to the highly mutagenic and carcinogenic 1,3-dichloroacetone or formation of epichlorohydrin or other genotoxic compounds play a role for mutagenicity and genotoxicity. In our studies, no indications of ADH catalysed formation of 1,3-dichloropropane could be found, although we could demonstrate a clear activation by ADH in the case of 2-chloropropenol. Formation of allyl chloride could also be excluded. We found, however, clear evidence that epichlorohydrin formed chemically in the buffer and medium used in the test is responsible for genotoxicity. No indication was found that enzymatic formation of epichlorohydrin plays a role. Additional mutagenicity and genotoxicity studies with epichlorohydrin also confirmed the hypothesis that genotoxic effects of 1,3 DCP-OH depend on the chemical formation of epichlorohydrin. PMID- 1913980 TI - Oral glutathione increases tissue glutathione in vivo. AB - Mice were given an oral dose of glutathione (GSH) (100 mg/kg) and concentrations of GSH were measured at 30, 45 and 60 min in blood plasma and after 1 h in liver, kidney, heart, lung, brain, small intestine and skin. In control mice, GSH concentrations in plasma increased from 30 microM to 75 microM within 30 min of oral GSH administration, consistent with a rapid flux of GSH from the intestinal lumen to plasma. Under these GSH-sufficient conditions, no increases over control values were obtained in GSH concentrations in most tissues except lung over the same time course. Mice pretreated for 5 days with the GSH synthesis inhibitor, L buthionine-S,R-sulfoximine (BSO, 80 mumol/day) had substantially decreased tissue concentrations of GSH. Oral administration of GSH to these GSH-deficient animals gave statistically significant increases in GSH concentrations in kidney, heart, lung, brain, small intestine and skin but not in the liver. Administration of the equivalent amount of the constituent amino acids, glutamate, cysteine, and glycine, resulted in little change in GSH concentrations in all tissues in GSH deficient animals. Thus, the results show that oral GSH can increase GSH concentrations in several tissues following GSH depletion, such as can occur in toxicological and pathological conditions in which GSH homeostasis is compromised. PMID- 1913981 TI - Quantitative and kinetic examination of 32P-postlabeling of etheno-substituted nucleotides. AB - 1,N6-ethenodeoxyadenosine-, 1,N2-ethenodeoxyguanosine- and 3,N4 ethenodeoxycytidine-3'-monophosphates were labeled by [gamma-32P] ATP using T4 polynucleotide kinase in conditions commonly used for the 32P-postlabeling assay. Kinetic studies showed that the reaction is fast reaching a plateau after 15-30 min. The efficiency of phosphorylation, as studied by substrate-product concentration dependency, was between 50-100% at the lower substrate concentrations. The adducts are labeled efficiently at sub-femtomole levels. All the adducts were sensitive to the 3'-dephosphorylation by P1 nuclease although the guanine derivative appeared to be more resistant than the two other adducts. PMID- 1913982 TI - Sleep related disorders of breathing. PMID- 1913983 TI - Health and economics. 1. PMID- 1913984 TI - Allergic bronchopulmonary aspergillosis among asthmatics. AB - Allergic bronchopulmonary aspergillosis (ABPA), an immunologically mediated lung disease is now well recognised as a significant cause of chronic lung disease in the West. This study aimed at determining the extent of this entity in 540 patients with severe bronchial asthma and 96 patients with mild or moderate asthma. Of these 134 were subjected to detailed examinations in the form of a skin test, serological test, sputum examination and peripheral blood eosinophil count. Eight patients (1.2% of the total and 6% of selected patients) had evidence of ABPA. A further 50 patients (8% of total and 37% of selected patients) had evidence of allergy to the fungus as depicted by positive skin test reactivity. The latter patients could be either early ABPA or potential candidates for the development of ABPA later. Skin test sensitivity to both Aspergillus fumigatus and A niger were demonstrated in Sri-Lankan asthmatics. Skin test sensitivity could be considered a screening test for the diagnosis of ABPA. A scheme for the diagnosis of ABPA using simple criteria could be devised keeping in mind the cost and availability of tests. PMID- 1913985 TI - A secondary analysis of determinants of low birth weight. AB - Data from 245 children of low birth weight on estates in Kalutara and Nuwara Eliya are analysed in relation to age, parity, and work load of the mother during pregnancy. A multivariate analysis shows that the last birth interval and the number of visits to the clinic are important variables besides variables like duration of pregnancy, poor weight gain and previous abortions. PMID- 1913986 TI - Elevated tumour necrosis factor in dengue fever and dengue haemorrhagic fever. AB - Acute and convalescent phase blood samples from five dengue fever (DF) patients and four dengue haemorrhagic fever (DHF) patients were tested for the presence of tumour necrosis factor (TNF). While all blood samples showed elevated levels, the acute phase blood sample levels were much higher. The mean TNF level in the acute samples of the five DF cases was 862 while in the DHF cases the level was 1722 pg/ml. Though the sample size is small, the difference appears to be statistically significant. Unlike in DF the distinctive features in DHF are the occurrence of shock, thrombocytopaenic purpura and sometimes disseminated intravascular coagulation (DIC). Increased TNF levels have not been reported in the literature in association with DHF, although it has been shown to contribute to these features which appear in some other diseases. PMID- 1913987 TI - Immersion warming of blood before transfusion. AB - We compared a simple method of warming stored blood by immersion of blood bags in warm water, to the standard method using portex blood warming infusion coils, which are not freely available in Sri Lanka. The mean temperature of blood after warming by immersion of blood bags was 29.5 degrees C and by infusion coil 30.2 degrees C. The values were within the confidence limits of each other. Ten units of blood in each group were compared with regard to changes in free haemoglobin (Hb), packed cell volume (PCV), and hydrogen ion concentration, and no statistically significant difference was observed. We recommend immersion warming as a safe and effective alternative to warming by infusion coil. PMID- 1913988 TI - Should we screen for scoliosis in Sri Lanka? PMID- 1913989 TI - Intestinal immunoregulation. PMID- 1913990 TI - Finger clubbing in match factory workers in Fiji. AB - This communication reports of two cases of digital clubbing in a factory manufacturing matches in Vitilevu, Fiji Islands. Both these cases were occupationally exposed to chemicals used in the manufacture of matches. They had physical contact with these chemicals including rhodamine B dye. Subjects who worked in the same factory area, including one worker who had FEV1.0 and FVC values below the predicted normal, but who did not handle chemicals showed no evidence of finger clubbing. PMID- 1913991 TI - Autonomic neuropathy--a preventable cause of death in tetanus. AB - A patient with autonomic neuropathy complicating tetanus is presented. The recognition and management of this potentially reversible complication is discussed. PMID- 1913992 TI - History of teaching hospitals in Sri Lanka. General Hospital Colombo (2). PMID- 1913993 TI - My impressions of Sri Lanka (2). An open letter. PMID- 1913994 TI - Woodfordin D and oenothein A, trimeric hydrolyzable tannins of macro-ring structure with antitumor activity. AB - Two new antitumor trimeric hydrolyzable tannins, woodfordin D (5) and oenothein A (13), were isolated from the dried flowers of Woodfordia fruticosa, and their macrocyclic structures, which have a novel constituent unit (woodfordinoyl group) connecting the monomers, have been elucidated on the basis of spectral and chemical evidence. Oenothein A (13) was also isolated from the leaves of Oenothera biennis. PMID- 1913995 TI - Marine natural products. XXVI. Biologically active tridecapeptide lactones from the Okinawan marine sponge Theonella swinhoei (Theonellidae). (2). Structures of theonellapeptolides Ia, Ib, Ic, and Ie. AB - Five tridecapeptide lactones, named theonellapeptolides Ia (1), Ib (2), Ic (3), Id (4), and Ie (5), were isolated from the Okinawan marine sponge Theonella swinhoei. Following the structure elucidation of theonellapeptolide Id (4), the structures of theonellapeptolides Ia (1), Ib (2), Ic (3), and Ie (5) were determined on the basis of chemical and physicochemical evidence including high performance liquid chromatography and circular dichroism combined analysis of the amino acid compositions. Theonellapeptolides Ib (2), Ic (3), Id (4), and Ie (5) exhibit moderate cytotoxic activity towards for L1210 in vitro (IC50 1.6, 1.3, 2.4, and 1.4 micrograms/ml, respectively), and theonellapeptolide Ie (5) exhibits ion-transport activities for Na+ and K+ ions. PMID- 1913996 TI - Structures of two new fibrinolytic saponins from the seed of Luffa cylindrica Roem. AB - Two new fibrinolytic saponins, lucyosides N and P, were isolated from the seeds of Luffa cylindrica Roem. (Cucurbitaceae). On the basis of chemical and spectral evidence, lucyoside N was characterized as 3-O-beta-D-galactopyranosyl-(1----2) beta-D-glucuronopyranosyl-28- O-beta-D-xylopyranosyl-(1----4)-[beta-D glucopyranosyl-(1----3)]-alpha-L -rhamnopyranosyl-(1----2)-alpha-arabinopyranosyl quillaic acid. Lucyoside P was characterized as a gypsogenin glycoside with the same sugar moiety as lucyoside N. PMID- 1913997 TI - New hypocholesterolemic abietamide derivatives. II. Synthesis and hypocholesterolemic activity of N-phenyl-delta 8-dihydroabietamides. AB - A series of N-phenyl-delta 8-dihydroabietamide analogs were prepared and tested for hypocholesterolemic activity. The effects of substituents of the phenyl moiety on the activities were quantitatively analyzed by using various substituent parameters. The activities were enhanced by the electron-donating effect of ortho and para substitutents and the bulkiness of ortho substituents. A combination of 2,6-dimethylaniline with resin acids other than delta 8 dihydroabietic acid produced lower activities than N-(2,6-dimethylphenyl)-delta 8 dihydroabietamide, abietane-type carboxamides being somewhat stronger than pimarane-type carboxamides. The conversion of the carboxamide group to other groups resulted in more or less of a decrease in activity, giving evidence that the carboxamide group is important to hypocholesterolemic activity. PMID- 1913998 TI - Studies on Balanites aegyptiaca fruits, an antidiabetic Egyptian folk medicine. AB - An aqueous extract of mesocarps of the fruits of Balanites aegyptiaca exhibited a prominent antidiabetic activity by oral administration in streptozotocin induced diabetic mice. From one of the active fractions of this extract, two new steroidal saponins were isolated, and their structures were determined as 26-O beta-D-glucopyranosyl-(25R)-furost-5-ene-3 beta,22,26-triol 3-O-[alpha-L rhamnopyranosyl-(1----2)]-[beta-D-xylopyranosyl-(1---- 3)]-[alpha-L rhamnopyranosyl-(1----4)]-beta-D-glucopyranoside and its 22-methyl ether. In addition, two known saponins, 26-O-beta-D-glucopyranosyl-(25R)-furost-5-ene-3 beta,22,26-triol 3-O-(2,4-di-O-alpha-L-rhamnopyranosyl)-beta-D-glucopyranoside and its methyl ether were isolated and identified. It was revealed that the individual saponins did not show antidiabetic activity, while the recombination of these saponins resulted in significant activity. From an ethanolic extract of the epicarps, two known flavonol glycosides, isorhamnetin-3-O-robinobioside and isorhamnetin-3-O-rutinoside were isolated and identified. PMID- 1913999 TI - Phenolic constituents of licorice. III. Structures of glicoricone and licofuranone, and inhibitory effects of licorice constituents on monoamine oxidase. AB - Two new phenolic compounds, glicoricone (3) and licofuranone (4), were isolated from a species of licorice brought from the northwestern region of China, and their structures were assigned. Among the twelve licorice constituents examined for the inhibition of monoamine oxidase (MAO), six compounds, 3, 4, genistein (6), licopyranocoumarin (7), licocoumarone (14) and glycyrrhisoflavone (15), inhibited the enzyme with the IC50 (concentration required for 50% inhibition of the enzyme activity) values of 6.0 x 10(-5)-1.4 x 10(-4) M. Glycyrrhizin (1) also inhibited MAO with the IC50 value of 1.6 x 10(-4) M. PMID- 1914000 TI - The complete amino acid sequence of an abortifacient protein, karasurin. AB - The complete amino acid sequence of a new abortifacient protein, karasurin, was determined. Karasurin, which was isolated from fresh root tubers of Trichosanthes kirilowii Maximowicz var, japonicum Kitamura (Cucurbitaceae), was a highly basic protein with pI 10.1 and molecular weight of 28,000. Intact karasurin was cleaved with cyanogen bromide, lysyl endopeptidase, formic acid and 2-(2'-nitrophenyl sulfenyl)-3-methyl-3-bromoindolenine (BNPS-skatole), respectively. Cleavages with N-bromosuccinimide (NBS), trypsin and pepsin were performed for the fragments. The resultant peptide fragments were separated by gel filtration chromatography, reversed-phase high performance liquid chromatography (HPLC) or gel filtration HPLC following sequence analyses by automated Edman methods. Karasurin consists of 246 or 247 amino acid residues with a calculated molecular weight of 27,144 or 27,215 differing only at the C-terminus with the addition of alanyl residue. Two C-terminal sequences were identified as Asn-Asn-Met-OH and Asn-Asn-Met-Ala-OH by sequence analyses and hydrazinolysis, but there was no micro-heterogeneity in other peptides analysed. The sequence of karasurin revealed a considerable similarity to that of trichosanthin and alpha-trichosanthin, which are known as abortifacient, ribosome-inactivating and anti human immunodeficiency virus (HIV) (the virus causing acquired immunodeficiency syndrome (AIDS) proteins, with 93% and 98% identity, respectively. PMID- 1914001 TI - Characteristics of peroxisome proliferation: co-induction of peroxisomal fatty acid oxidation-related enzymes with microsomal laurate hydroxylase. AB - The profile of the changes in the peroxisomal fatty acid oxidation activity in rat liver was compared with that in microsomal omega-oxidation under various conditions such as a 2-week administration of phenoxyacetic acid derivatives and perfluorinated compounds, short and long-term administration of clofibrate and bezafibrate, high-fat diet feeding, starvation and diabetes. The results were summarized as follows: 1) when phenoxyacetic acid derivatives and perfluorinated compounds were administered, there was a significant correlation in the increase of the activities between peroxisomal fatty acid oxidation and microsomal omega oxidation. 2) On the long-term administration (79 weeks) of peroxisome proliferators the activities of the enzymes were significantly reduced, but the levels were still higher than the control level in a similar manner. 3) On high fat diet feeding the patterns of the changes in the activities of peroxisomal fatty acid oxidation, carnitine acetyltransferase and microsomal omega-oxidation were similar to each other, differing from the changes in the activities of microsomal aminopyrin demethylase and mitochondrial carnitine palmitoyltransferase. 4) Under starved and diabetic conditions, co-induction of peroxisomal fatty acid oxidation and microsomal omega-oxidation was observed. From these results it is suggested that 1) the biosynthesis of these enzymes would be regulated on the gene expression of the nearby domain and 2) peroxisomal fatty acid oxidation and microsomal omega-oxidation were co-operatively regulated in order to achieve fatty acid metabolism smoothly. PMID- 1914002 TI - Contribution of glycation to human lens coloration. AB - To study the contribution of glycation or the Maillard reaction to the spontaneous coloration of human crystalline lens in aging, we determined 1 deoxyfructosyl adduct and the fluorescent material, which are produced in the early stage of glycation, in the proteins of normal and colored human lenses of different ages. The amount of both glycation products in the lens increased significantly in proportion to aging or the advance of lens coloration. The insolubility of lens protein also increased with the advance of glycation. In addition, the present study showed that glucose and glucose-6-phosphate have higher reactivities with human lens protein than fructose and glucose-1 phosphate. This paper demonstrates that the deeper colored or older aged lens contains larger amounts of glycation products, and that glycation between lens protein and various sugars in vivo may be a serious factor in human lens coloration or insolubilization of lens protein. PMID- 1914003 TI - Esterase-like activity of human serum albumin. VII. Reaction with p-nitrophenyl 4 guanidino-benzoate. AB - The reaction of p-nitrophenyl 4-guanidinobenzoate (NPGB) with human serum albumin (HSA) was examined kinetically at various pH's and 25 degrees C. The Michaelis constant (Ks in M) and the catalytic rate constant (k2 in s-1) were determined. The ratio of k2 to k0 (hydrolysis rate constant of NPGB in s-1) at pH 7.4 was 75.6, indicating the esterase-like activity of HSA. The effects of the reversible binding of site-specific drugs and the chemical modification by site-specific reagents on the HSA activity indicated that HSA has multiple reactive sites towards NPGB. Results of the reaction in the presence of excess NPGB over HSA also suggested the existence of multiple active sites. The pH-profile for k2 showed inflection points at about pH 6.0 and pH 10.0, suggesting the involvement of groups with pKa's of 6.0 and 10.0 in HSA. PMID- 1914004 TI - Inhibition of endothelin (ET)-1-and ET-2-induced vasoconstriction by anti-ET-1 monoclonal antibody. AB - We produced a monoclonal antibody to endothelin (ET)-1, tested cross-reactivities with the related peptides by enzyme immunoassay, and investigated the effects of the antibody on ET-1- or ET-2-induced vasoconstriction of rat isolated thoracic aorta. The antibody recognized ET-1, ET-2 and ET-3, and the immunoreactive site proved to be the N-terminal region but not the C-terminal region of ET-1. Moreover, at an approximate molar-equivalent concentration, the antibody absorbed ET-1 and ET-2, and significantly inhibited ET-1- and ET-2-induced vasoconstriction notwithstanding the presence of the endothelin receptor. PMID- 1914005 TI - Lipid A and related compounds. XXVI. Syntheses of biologically active penta-O acetyl-N-glycoloylneuraminyl- and penta-O-acetyl-3-deoxy-D-galacto-2- nonulopyranosonic acid-(alpha 2----6)-D-glucosamine-4-phosphate analogs of lipid A. AB - The syntheses of novel penta-O-acetyl-N-glycoloylneuraminyl- and penta-O-acetyl-3 deoxy-D-glycero-D-galacto-2-nonulopyranosonic acid-(alpha 2----6)-D-glucosamine-4 phosphate analogues of lipid A containing sialic acid in place of 3-deoxy-D-manno 2-octulosonic acid are described. Preliminary examination of the biological activity revealed that two synthetic disaccharides showed mitogenic activities and weak antitumor activities. PMID- 1914006 TI - Gardenia fruit extract does not stimulate the proliferation of cultured vascular smooth muscle cells, A10. AB - We investigated the effect of a hot water extract from Gardenia fruit (Gardenia jasminoides Ellis) (GFE), which has a stimulatory effect on endothelial cell proliferation, on the proliferation of A10 cells, an established cell line of vascular smooth muscle cell from murine aorta in a culture system. GFE did not change the number of A10 cells after a 48 h culture. GFE significantly increased the incorporation of [3H]thymidine and [14C]leucine into the acid-soluble fraction of bovine aortic endothelial cell layers, but significantly decreased that of A10 cells. These results suggested that GFE stimulates the proliferation of endothelial cells but not of A10 cells. In the endothelial cell culture, GFE significantly increased the accumulation of basic fibroblast growth factor, which is an autocrine for endothelial cell proliferation in medium and low-affinity (glycosaminoglycans-binding) fractions, while A10 cells did not produce a significant amount of the factor. Since it is postulated that a selective stimulation of endothelial cell proliferation by increasing the production of basic fibroblast growth factor is appropriate for prevention of arteriosclerosis and thrombosis, GFE may contain a beneficial component as a useful drug. PMID- 1914007 TI - Chemiluminescence assay of N-acetyl-beta-D-glucosaminidase in urine using o aminophthalylhydrazido-N-acetyl-beta-D-glucosaminide. AB - The chemiluminescence assay of urinary N-acetyl-beta-D-glucosaminidase using o aminophthalylhydrazido-N-acetyl-beta-D-glucosaminide as the substrate was examined. Under optimized conditions, a linear chemiluminescence response to the standard N-acetyl-beta-D-glucosaminidase (NAGase) of different concentrations was observed with a correlation coefficient of 0.999 over the range of 0.3 to 20 I.U./l. The present method was compared with the prevalent method using p nitrophenyl-N-acetyl-beta-D-glucosaminide in the assay of 20 urine samples from healthy subjects, and the correlation coefficient of 0.891 was obtained. PMID- 1914008 TI - Co-suppression by nicardipine, a calcium antagonist, of induction of microsomal lauric acid hydroxylation with peroxisome proliferation in clofibrate-treated rat liver. AB - The in vivo effect of nicardipine, a well-known calcium antagonist, on microsomal omega-oxidation of laurate in clofibrate-treated rat liver was studied. The 15.3 fold induction of the activity by 2 weeks administration of 0.25% clofibrate in the diet was markedly suppressed to about 6-fold by co-administration of nicardipine at 100 mg/kg body weight. Similarly, the induction of peroxisomal beta-oxidation and carnitine acetyltransferase activities were also suppressed by this simultaneous administration by more than 50%. Although clofibrate also induced the activity of reduced nicotineamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase and increased the hepatic content of cytochrome P 450, no suppressive effect of nicardipine was observed. Contrarily, nicardipine induced the reductase activity and increased the hepatic content of cytochromes P 450 and b5. These results provide the first demonstration of a calcium antagonist, e.g. nicardipine acting as inhibitor of the induction of microsomal omega-oxidation, in association with the inhibition of peroxisome proliferation in animals. The suppression of drug-induced peroxisome proliferation and microsomal omega-oxidation by the calcium antagonist may help in elucidating the causal relationship of the induction mechanisms between peroxisomal and microsomal enzymes. PMID- 1914009 TI - The growth inhibition of Streptococcus mutans by 5'-nucleotidase inhibitors from Areca catechu L. AB - New 5'-nucleotidase inhibitors named NF-86I, NF-86II were recently isolated from the seeds of Areca catechu L. NF-86I and NF86II showed inhibitory effects on the growth of Streptococcus mutans MT8148(c) and Streptococcus mutans MT6715(g), respectively. In addition, these inhibitors could inhibit insoluble glucan formation from sucrose. NF-86I and NF-86II were found to be polyphenolic substances. Some polyphenols such as tannic acid bind non-specifically to proteins (tannic activity). The 5'-nucleotidase inhibitors that we isolated did not show any such activity. However, the growth inhibitory activity and the inhibitory effect on water-insoluble glucan production were equal to tannic acid. It is therefore considered that these inhibitors bind specifically to the bacterial cell surface. Our findings suggest that the 5'-nucleotidase inhibitors NF-86I and NF-86II may be useful anti-plaque preventing agents. PMID- 1914010 TI - Formycin A resistant mutants due to defect in adenosine transport system in Vibrio parahaemolyticus. AB - An antibiotic formycin A inhibited growth of Vibrio parahaemolyticus under certain conditions, which suggested that formycin A was taken up by cells under these conditions. We found that formycin A was transported via the adenosine transport system which we previously reported as a Na(+)-coupled cotransport system. We isolated many formycin A resistant mutants, and about half of them grew very poorly on adenosine as a sole source of carbon. Judging from their reversion frequencies, these mutants seemed to have single mutations. Respiration driven uptake of 14C-adenosine was not observed in such mutants; also, Na+ uptake induced by the addition of adenosine or formycin A to a cell suspension was completely abolished in them. Thus we conclude that these mutants possess a defect in the Na+/adenosine cotransport system, and have become formycin A resistant. PMID- 1914011 TI - Evaluation of low-molecular gelatin as a pharmaceutical additive for rapidly absorbed oral dosage formulation. AB - The dissolution behavior of ibuprofen from a kneaded mixture with low-molecular gelatin (LM gelatin) has been studied in comparison to kneaded mixtures prepared with other additives. Their in vivo absorption behaviors were also examined. The LM gelatin markedly enhanced the dissolution rate of ibuprofen compared to that with polyethylene glycol (PEG) 6000, dextran T10 or pullulan. Oral administrations of the kneaded mixture to beagle dogs showed the LM gelatin to be most effective in accelerating the absorption rate of ibuprofen among the additives used. PMID- 1914012 TI - Permeability of glycosides through human erythrocyte membrane. AB - The permeability of glycosides (arbutin, salicin, glycyrritin, p-nitrophenyl-beta D-glucopyranoside, p-nitrophenyl-beta-D-galactopyranoside, p-nitrophenyl-beta-D lactopyranoside, p-nitrophenyl-beta-D-maltopyranoside) and their aglycons through human erythrocyte membrane was investigated. The glycosides permeated slowly, compared with their aglycons. Glycoside having disaccharide did not permeate the erythrocyte membrane. This suggested that the introduction of disaccharide to a drug significantly depresses the permeability of glycoside through erythrocyte membrane. The drug entrapped in erythrocytes was not released into the outer medium. PMID- 1914013 TI - [The effect of free radicals on the rabbit articular chondrocytes in monolayer culture]. AB - By using monolayer culture technique, the effect of endogenous free radicals on rabbit articular chondrocytes was studied. The free radicals were provided through the action of xanthine oxidase (XO) on xanthine (X). The amount of DNA in chondrocytes was measured with ethidium bromide method for direct fluorometric estimation of DNA. The synthesis of proteoglycan (PG) was assayed through 35S Na2SO4 incorporation followed by inverted microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results indicated that chondrocytes could be damaged by endogenous free radicals generated by the action of XO on X, and these free radicals may be related to the pathogenesis of cartilage aging, degeneration, degenerative joint disease and arthritis. PMID- 1914014 TI - [Pathomorphologic and immunohistochemical study of midline malignant reticulosis]. AB - The histopathology, immunophenotype and clinical presentation in 35 cases of midline malignant reticulosis (MMR) were studied with 8 cases of midfacial non specific inflammation as the control during immunohistochemical staining. The result showed that atypical lymphoid cells (ALC) of MMR could be divided into small, intermediate and large ALC subtypes basing on their sizes. Twenty-three of the 35 cases (65.7%) showed dominant small and medium-sized ALC proliferation, meanwhile, ALC infiltrating into the mucosa and vascular walls were also small and medium-sized cell predominant. Immunohistochemical study showed that the UCHL1 positive small lymphocytes proliferated predominantly in MMR; in contrast, many Ki-B5 positive lymphocytes appeared in midfacial inflammation. ALC of MMR in 27 cases (71%) also showed UCHL1 positive reaction but negative reaction to Ki-B5 and lysozyme. The result indicates that ALC of MMR belongs to T-lymphocyte origin and MMR may be a kind of peripheral T-cell lymphoma originated from mucosa associated lymphoid tissue (MALT). The relations between MMR, malignant lymphoma and other related disorders of MALT are discussed. PMID- 1914015 TI - [A study on the relationship among estrogen receptor, progesterone receptor and glucose-6-phosphate dehydrogenase activity in primary breast cancer]. AB - The relationships among estrogen receptor (ER), progesterone receptor (PgR) and glucose-6-phosphate dehydrogenase (G6PD) activity demonstrated by histochemical technique were studied in 85 cases of primary breast cancer. The ER positive rate was 71.8% and the PgR positive rate was 54.1%. A close correlation was obtained between the PgR and ER positivity or the semiquantitative grades. The G6PD activity in ER or PgR positive group was higher than that in the negative group. Moreover, the elevated G6PD activity was also correlated with the increased semiquantitative grades of ER or PgR. Our findings support the views that both PgR and G6PD are proteins induced by estrogen and may represent markers of functional ER in breast cancer. This suggests that simultaneous assay of ER, PgR and/or G6PD activity may be more reliable to predict the hormone dependence of the tumor. PMID- 1914016 TI - [Pathologic study on megakaryocytes in chronic myeloproliferative disorders]. AB - Megakaryocytes in 42 cases of Chronic Myeloproliferative Disorders were studied pathologically, and a classification of these disorders was suggested. Abnormal megakaryocytes were classified as immature, mature, naked-nuclear, micro-, giant, multinucleated and dysplastic types based on the degree of maturity, the number of ploidy, and the presence or absence of atypia. Immunohistochemical studies indicated that antibodies against platelet glycoprotein Ib, IIb/IIIa as well as VIII R:Ag are highly specific for the detection of megakaryocytes, especially the morphologically unrecognizable ones. With regard to the identification of micromegakaryocytes, nuclear size, shape and degree of cytoplasmic maturity were emphasized. In addition to the classification, the clinic-pathological significance of abnormal megakaryocytes is discussed. PMID- 1914017 TI - [An ultrastructural and immunohistochemical observation of squamous cell carcinoma of the lung with neuroendocrine differentiation]. AB - Thirteen cases (10.5%) of squamous cell carcinoma of the lung with neuroendocrine differentiation were identified ultrastructurally in 124 cases of resected pulmonary carcinoma. In addition to the features of epidermoid differentiation, i.e. presence of tonofilaments and desmosones, a small amount of cancer cells containing neurosecretory granules were found in all the 13 cases. Ultrastructures indicated that both epidermoid and neuroendocrine differentiations were present simultaneously in individual cancer cell. Immunohistochemical staining for NSE was performed in 12 cases. Positive reaction was obtained in all but one (91.7%). NSE positive cancer cells distributed focally or in single cell scattered in the cancer cell nests. The results suggest that biphasic differentiation of pulmonary squamous cell carcinoma diagnosed by light microscopy may not originate from different cells of different derms, but may be derived from a common stem cell of the bronchial epithelium which possesses the ability of multipotential differentiation. PMID- 1914018 TI - [The effect of neutral fraction of cigarette smoke condensate on DNA content of hamster's tracheal epithelial cells]. AB - Histologic changes and DNA content alterations of hamster's tracheal epithelial cells induced by Benzo(a)pyrene[B(a)P] and/or the neutral fraction of cigarette smoke condensate (CSC-NF) in organ culture were investigated by light microscopy and automated image analysis technique. The results showed that B(a)P + CSC-NF induced severe atypical hyperplasia of the epithelium. Additionally, the DNA content and the percentage of cells with aneuploid DNA content also increased significantly. The histogram of DNA distribution became apparently widened. The high peak was shifted to the right and many irregular median and low peaks were also obtained. PMID- 1914019 TI - [A morphological study of primary pulmonary hypertension: an analysis of five autopsies]. AB - Five autopsy cases of typical primary pulmonary hypertension are reported. The histopathological features were as follows: marked medial hypertrophy of muscular pulmonary arteries; muscularization of arterioles; intimal fibrosis and fibroelastosis of muscular pulmonary arteries accompanied by a typical onion skin configuration. The plexigenic pathological change is considered to be the result of response, at the late stage, to pulmonary hypertension rather than due to congenital abnormality or embolism. PMID- 1914020 TI - [Effect of duokang jiasu on the cytotoxicity of peripheral blood mononuclear cells]. AB - Duokang Jiasu, a biological reaction modifier widely used in cancer clinics, has been proved that its tumor suppression effect is based on the macrophage activity. The results of this study showed that monocytes treated with Duokang jiasu in vitro has much stronger cytotoxicity against allogenic tumor cells. Incubation of mononuclear cells with Duokang jiasu beforehand could promote both NK and ADCC activities. PMID- 1914021 TI - [Effect of selenium on myocardial function and structure in mice within ischemic and hypoxic environment]. AB - The experiment was designed to study the protective effect of selenium on myocardial function and ultrastructure changes of fetal mouse heart model under ischemic and hypoxic circumstances. The results showed that selenium can prolong the period of heart surviving and beating. Results via lanthanum probe technique indicated that selenium is able to maintain the functional integrity of the myocardial cell membrane as well as the mitochondria membrane. Ultrastructure changes under REM suggested that selenium may play a role in delaying the development of irreversible myocardial injury and to promote protein synthesis and the repairment of the injured cells. PMID- 1914022 TI - [A pathohistological study on experimental brucellosis in inbred mice]. AB - A pathohistological study was carried out in BALB/C and C57/BL inbred mice models infected with B. melitensis, B. abortus, and B. suis respectively. The results showed that a chronic pathological lesion was developed due to repeated infectious processes occurred in various organs at different stages of brucella infection. Significant pathological changes was observed in the reticuloendothelial system including the lymphocytes, spleen and liver etc. and less remarkable changes were seen in the lung, heart and kidney in sequence. Comparing the pathological changes induced by the three species of brucella infection, lesions developed in BALB/C was more remarkable and the pathological change induced by B. abortus infection was the most significant in both BALB/C and C57/BL mice. PMID- 1914023 TI - [Progress in the pathologic research of gastric mucosa disorders]. PMID- 1914024 TI - [Dynamic changes of Ito cells in experimental cirrhosis of rat]. AB - That Ito cells in rat liver express desmin was confirmed by immunohistochemical technique. Anyhow, changes of desmin-positive cells, lysozyme-positive cells and fibronectin were further studied in experimental cirrhosis of rat. It was found that desmin-positive cells, with the transitional features between Ito cells and myofibroblasts or fibroblasts under electron microscope, increased in number and expression of desmin in the necrotic areas as well as in the cellular fibrous septa, but decreased in number in the fibrous septa except those areas close to the edges of the septa. These results suggested that Ito cells, myofibroblasts and fibroblasts may belong to the same cellular system and play an important role in the pathogenesis of cirrhosis. Meanwhile, it was also noted that changes of both fibronectin and lysozyme-positive cells were correlated with those of desmin positive cells. These provide evidence in vivo that fibronectin and Kupffer cells may exert certain effects on the migration and proliferation of Ito cells in cases of liver cirrhosis. PMID- 1914025 TI - [Immunohistochemical observation on the proliferative activity of rat liver in early hepatocarcinogenesis]. AB - Anti-BrdU immunoperoxidase staining was used for cytogenetic investigation of altered foci and nodules in rat liver induced by a procedure including intraperitoneal injection of diethylnitrosamine (DEM), feeding of 2 acetoaminoflurene (2-AAF) and 2/3 hepatectomy. Variation in number and size of the altered foci as well as the number of BrdU-positive hepatocytes inside and outside the foci were clearly observed in the early stage of hepatocarcinogenesis. A predominant distribution of BrdU-positive cells was obtained in the peripheral zone of the altered nodules favorable in explaining the phenomenon of monoclonal origin of the altered hepatocytes inside the nodules. This study also indicated that BrdU-immunoperoxidase staining is a reliable and convenient method in studying the dynamic change of DNA-replication in the process of active hepatocellular proliferation. PMID- 1914026 TI - [Diet regulation during pregnancy complicated with diabetes]. PMID- 1914027 TI - [Injury of tubo-optic nerve treated by decompression of tubo-optic nerve through naso antra]. PMID- 1914028 TI - [Effect of table salt on liquid nitrogen refrigeration therapy in skin diseases]. PMID- 1914029 TI - [Research on the nursing stroke patients during past 10 years]. PMID- 1914030 TI - [Quality of BCG vaccinations for newborns]. PMID- 1914031 TI - [Clinical and experimental studies of rheum on preventing progression of chronic renal failure]. AB - Rheum, a well known herb unique in its cathartic effect is now introduced to prevent progression of uremia. A clinical prospective trial was conducted to evaluate its effect in comparison with the Captopril. 30 cases with initial Scr level of 344.8 +/- 114.0 mumol/L were allocated randomly to 3 groups. Rheum E treated group, Captopril treated group and Rheum E + Captopril group. The long term (6-22 mos) follow-up results showed that the progression rate of renal failure, calculated by regression analysis of 1/Scr vs time, was found to be retarded after treatment, being more marked in both Rheum E and Rheum E + Captopril group. Uremic symptoms improved after the treatment with serum albumin level increased. To explore the mechanism of therapeutic effects of Rheum on CRF, a series of experimental studies were performed. Rheum can suppress the proliferation of glomerular mesangial cells in culture. In 5/6 nephrectomized rats, the O2 consumption of remnant kidney was obviously decreased by feeding the animal Rheum E and the hypermetabolic state was ameliorated as well. A group of 5/6 nephrectomized rats were fed with Rheum E for 28 wks. It was found that the level of azotemia of this treated group was lessened remarkably as compared with the controls. The serum albumin and transferrin contents of the treated animals were much higher than the controls while the blood cholesterol and triglycerides decreased unexpectedly. In conclusion, both the in vivo and in vitro studies have proved the effectiveness of Rheum in preventing the progression of CRF. PMID- 1914032 TI - [Exploring the substantial basis of the features yinxu huowang in girls with precocious puberty]. AB - Differential diagnosis to 75 girls with true precocious puberty was made using method of TCM. It was observed that each girl had Yinxu Huowang (intense internal heat due to deficiency of vital essence) to a certain extent, these features were very remarkable in most of them. To explore the substantial basis of the features, the functions of hypothalamic-pituitary-ovarian axis were determined. The results showed that the levels of serum FSH, LH, E2 in the girls rise significantly than those in normal girls of the same age, and LHRH stimulating test displays characteristic changes of excessive activity. Treated with TCM of Ziyin Xiehuo, (nourish vital essence reducing intense internal heat) and remitted, the levels of serum FSH, LH, E2 descend significantly, the volume of uterus and ovary reduce markedly, secondary sexual characteristics retrogress evidently, while the features of intense internal heat due to deficiency of vital essence mitigate obviously. According to the above mentioned, the authors consider that the hypothalamic-pituitary-ovarian axis starting beforehand and being hyperfunction are likely to be the substantial basis of the features--that deficiency of Shen Yin, (vital essence) accompanied with intense Fire of the Vital Gate--of the girls with true precocious puberty. PMID- 1914033 TI - [Treatment of breast proliferation disease with modified xiao yao san and er chen decoction]. AB - The authors report the 3 months' treatment of 51 cases of breast proliferation disease with modified Xiao Yao San and Er Chen decoction, an effective rate being 96.1%. In each patient before and after treatment, saliva estradiol (SE2), saliva progesterone (SP), saliva testosterone (ST) and plasma prolactin (PRL) concentrations were monitored and breast molybdenum-target X-ray films were taken. The results showed that after treatment, SE2 concentrations declined very significantly (P less than 0.001); SP concentrations declined significantly (P less than 0.05); PRL concentrations declined very significantly (P less than 0.005), but ST concentrations did not change significantly. Breast molybdenum target X-ray films showed absorption of proliferation masses in 21 cases. These indicated that the medicine could regulate endocrine system, perhaps through suppressing secretion of PRL, decreasing prolactin antagonist action to follicular stimulating hormone so as to restore follicle function, and could regulate pituitary-follicle axis and make the axis normal. PMID- 1914034 TI - [Effect of moxibustion on the antibody-dependent cell-mediated cytotoxicity activity in peripheral blood of patients with Hashimoto's thyroiditis]. AB - To investigate the immune regulating effect of moxibustion on the patients with Hashimoto's thyroiditis, 35 patients were treated by moxibustion and the changes of antibody-dependent cell-mediated cytotoxicity (ADCC) activity in the peripheral blood of the patients and their relationship with thyroid microsomal antibody (MCA) before and after treatment were observed. It was found that the activity of ADCC and the combining rate of MCA were higher than normal and they were closely related to each other. After treatment, both of them declined remarkably and the relationship between them remained the same. The result indicated that the treatment of Hashimoto's thyroiditis by moxibustion might well be related to its effect of decreasing the activity of ADCC and the titer of anti thyroid antibodies. PMID- 1914035 TI - [Superficial tongue blood volume and the tongue spectrophotometric determination on coronary heart disease with blood stasis syndrome]. AB - The tongue bodies of coronary heart disease (CHD) patients with blood stasis syndrome were looking dull purple in different degree. The authors adopted two kinds of biophysics methods which are tongue spectrophotometer and DM-80-6 superficial tongue blood volume meter. 52 CHD patients with blood stasis syndrome, 50 normal individuals and 26 patients before and after the treatment according to promote blood circulation to remove the blood stasis, were examined. The results were as follows: The purple ray values of the tongue spectrum of the CHD patients with blood stasis syndrome were more than that of normal individuals. Statistics showed significant difference (P less than 0.01). So was the tongue blood volume (P less than 0.01). In the treatment group, the purple ray value of tongue spectrum reduced, and the red ray volume of tongue increased significantly, as well (P less than 0.01). The results suggested that both methods may be quantitative comparative parameters for diagnosis, differentiation of symptoms and signs, and evaluation of the therapeutic effectiveness. PMID- 1914036 TI - [Effect of shen-qian gu-jing granule on fibrin degradation products in serum and menstrual fluid of patients with menorrhagia]. AB - Shen-Qian Gu-Jing granule was used in the treatment of the menorrhagia in 72 cases including idiopathic menorrhagia 28, uterine myoma 29, endometriosis 7, intrauterine device 5, postpartum and post induced abortion 3 cases. The amount of menstrual blood loss (MBL) and the fibrin degradation products (FDP) level in menstrual fluid and peripheral blood were measured before and after treatment. 87.5% of all cases showed a significant decrease in MBL (P less than 0.05). The local FDP level significantly decreased parallel to effectiveness of MBL. The results suggested that the function of this Chinese herbs complex in menorrhagia was related to the regulation of FDP level. PMID- 1914037 TI - [Clinical and experimental study on shenghong kangyan su in treating 144 cases of pelvic inflammation with blood stasis syndrome]. AB - Using the method of clearing up heat and resolving stasis, the authors treated 144 cases of pelvic inflammation with blood stasis syndrome (BSS) with Shenghong Kangyan Su. The total effective rate was up to 97.92%, cure rate up to 68.75%, without toxicity and side effects. Clinical and experimental study showed that the crux of pelvic inflammation with BSS had some relations with microcirculation obstruction. Inflammation may cause microcirculation obstruction and blood stasis, and is one forms of BSS. Therefore dull purple-tongue, undertongue vein dilated, abdominal pain in lower-part, pathologic mass can be regarded as the basis of diagnosis of pelvic inflammation with BSS The drug of clearing heat and resolving status has the functions of anti-inflammation, anti-pain, diminishing the obstruction of microcirculation, particularly in speeding up the blood flowing, lowering the aggregation of erythrocyte, P less than 0.001. PMID- 1914038 TI - [Comparison with the pharmacological actions of Morinda officinalis, Damnacanthus officinarum and Schisandra propinqua]. AB - There are three kinds of plants, Morinda officinalis (1), Damnacanthus officinarum (2), and Schisandra propinqua (3) whose roots have been used since the ancient time. In this paper, some of their pharmacological actions that are related to tonifying and invigorating Yang were examined and compared. The body weight, the thymus weight, the amount of leukocyte in the blood, and the continuing swimming times of the young mice could be increased with the oral administration of the water extractions of (1) and (2) (P less than 0.05-0.001). The Rt of M-receptor in the brains of the hypothyroidism mice were decreased after administration of the water extracts of (1) and (2) (P less than 0.05). (1) could also increased the amount of leukocyte in the blood of leukocytopenia mice caused by radiation of gamma-ray (P less than 0.01). (3) has not shown the obvious effects (P greater than 0.05). The results indicate that (1) and (2) have the ability of anti-fatigue, improving the immunological action of the young mice, and reducing the excitability of the para-sympathetic nervous system of the hypothyroidism mice through decreasing the Rt of M-receptor in their brains. All of them did not show acute toxicity, inducing mutation, and sexual hormone like actions. PMID- 1914039 TI - [Experimental study on the immunomodulatory effects of rhubarb]. AB - The immunomodulatory effects of Rhubarb on the murine functions are reported. Varying dosages of Rhubarb administrated orally were able to increase the delayed hypersensitivity response induced by bovine serum albumin and proliferation response of murine spleen cell to Con A and lipopolysaccharide. The above description indicate that Rhubarb could promote immune response. PMID- 1914040 TI - [Advance of screening for anti-candida agents from Chinese herbal drugs]. PMID- 1914041 TI - [Advances in the research on the treatment of arrhythmia with traditional Chinese medicine]. PMID- 1914042 TI - [Detection of HIV antibodies in a rural region of a developing country]. AB - A HIV seroprevalence among 312 antenatal mothers at their first visit to the Idjwi isle's hospital, in Zaire, near Rwanda, and among 61 other patients, was made with the HIV1 Immunocomb of PBS Orgenics during one year: 1989. The seroprevalence is 0.32%, in this rural area, as was confirmed by Western-Blot. A panel of this 51 "false and true positive" and 13 negative african sera was tested with one other ELISA and two new rapid tests used in France, HIV CHEK 1 + 2 and TEST PACK HIV1/HIV2 to evaluate efficacy under conditions in which transfusions are normally given. These were performed within 15 mn of receipt of blood from a donor in Zaire. PMID- 1914043 TI - [Candidiasis and AIDS in Yaounde]. AB - In this preliminary study, we discuss 9 cases of Candidosis diagnosed during a 6 month period in 32 AIDS patients hospitalized in three health Centers in Yaounde. Most of the patients presented with buccal candidosis and/or dysphagia. Of the 18 strains grown, 17 (94%) are Candida albicans. PMID- 1914044 TI - [Analysis of 190 strains of Neisseria gonorrhoeae isolated in Yaounde from 1984 to 1987: auxotypes, plasmidic contents, antibiotic sensitivity]. AB - Gonococcal infections are always a public health problem in Cameroon. From January 1984 to December 1987, 2,074 strains have been isolated in the "Centre Pasteur du Cameroun". Among these strains, 190 had been studied in details concerning antibiotic susceptibility, auxotypes and plasmidic content. Penicillinase producing Neisseria gonorrhoeae (PPNG) were increasingly isolated: 32.28% (1984); 59.57% (1987). Auxotypes prototrophes and proline requiring were more often isolated. Plasmidic content showed essentially african type (with or without conjugative plasmid) but also asian type. PMID- 1914045 TI - [Beta-lactam and aminoglycoside resistant phenotypes in enterobacteria isolated in pediatrics]. AB - Beta-lactams and aminoglycosides are widely used in the therapy of serious Gram negative infections in pediatrics. In order to survey acquired resistance, the phenotype of resistance to beta-lactams and aminoglycosides were characterized for 260 strains of enterobacteriaceae among the mainly isolated species in pediatrics. These phenotypes were established according to the results of the disk susceptibility tests for beta-lactams respectively ampicillin, ticarcillin, cefaloridin and cefotaxim, and aminoglycosides, streptomycin (S), gentamicin (G), tobryamycin (T), amikacin (A), and netilmicin (N). 49% of E. coli and 73% of P. mirabilis strains were resistant to 3 beta-lactams (RRRS). 72% of Salmonella spp. strains were resistant to 4 beta-lactams (RRRR). For the majority of strains, the mainly observed resistance phenotype to aminoglycosides was streptomycin resistance excepted for Salmonella spp., which was S + KGTNA. The high level of acquired resistance to beta-lactams and aminoglycosides among Enterobacteriaceae with the selection of multiresistant strains would be explained by the wild use of cefotaxim and amikacin in pediatrics. PMID- 1914046 TI - [Malaria of importation in the child: epidemiological, clinical and therapeutic analysis. Apropos of 70 cases observed in a pediatric hospital in Paris]. AB - Seventy children from 7 months to 15 years old have been treated for malaria at Hospital Trousseau (Paris) during years 1987 and 1988. Thirty nine of them were living in France usually. The infection was one chiefly in Africa (68 cases), and by P. falciparum in 78% of children. The digestive symptoms were frequent (40/70); splenomegaly was observed in 40 children and hepatomegaly in 31. Anemia was present in 59 cases and mild thrombopenia for 31 cases. The C. reactive protein raised in 92% of cases. The diagnosis was late in 31 patients. Only one cerebral malaria case was observed. The chemoprophylaxis was unfitted or absent in 74% of children living in Paris. The chloroquino-resistance was clinically present in 17 cases and the mefloquine was more often used during 1988 year. PMID- 1914047 TI - [Seroepidemiological study of urogenital schistosomiasis in Algeria: the focus of Khemis el Kechna]. AB - Two foci of schistosomiasis are known to be active in Algeria, first in the north of the country, at wadi El Hamiz in relation with the dam of El Hamiz river in the commune of Khemis el Kechna; and the other in the south, in the Tassili N'Ajjer region (Djanet, Iherir, Tamadjert). In relation with a preparatory phase of a control programme of the disease a sero-epidemiological study was performed in the focus of Khemis el Kechna in 1987-1988; 1,876 parasitological samples and 1,760 serological samples were collected. The parasitological prevalence was 4.90%, the serological prevalence was 15.6% with a wider distribution by age. PMID- 1914048 TI - [Epidemiology of intestinal schistosomiasis with Schistosoma mansoni in Richard Toll (Delta of the Senegal River). Malacological study]. AB - A recent outbreak of intestinal schistosomiasis (1989) has been reported in Richard-Toll (Delta of Senegal River) with a global prevalence of 43%. A malacological survey has been carried in order to study, the density of Biomphalaria pfeifferi the intermediate hosts, their distribution and rate of infection, and to identify the transmission sites. Ten districts have been selected. The snails have been collected in the different water points of these localities which are the river, the Taouey marigot, the Taouey channel and the irrigation channels and drains of the CSS (Senegal Sugar Company). A total of 1,210 Biomphalaria have been collected in 45 sites with a variable density of 2 to 150 snails. The overall rate of infestation of snails is 44% but varies according to the districts (9 to 64%). The transmission is acting in all the districts mainly in the Taouey channel (28% of infested snails) the Taouey marigot (38% of infested snails) and particularly in the channels of CSS (47% of infested snails). The situation is alarming and requires urgent action be undertaken to decrease the prevalence and reduce the transmission. PMID- 1914049 TI - [Epidemiology of intestinal parasitosis in Laos (with anti-amoebic antibody levels)]. AB - The overall prevalence rate of the intestinal parasites in Laos ranges from 76.8% to 95.7% depending on living conditions. The predominant species is Opisthorchis complex with the peak in age group greater than 20 years and infected in one village all men over 20 years. Unusually high frequency demonstrated Sarcocystis hominis as well as Taenia sp. with the culmination of infection among the adults. The habit of eating raw flesh of fish, beef and pork is responsible for the spreading of these three zoonotic parasitoses. The intimate coexistence between the domestic animals and man explains the prevalence of Trichostrongylus sp. Low infection rate as E. histolytica have been found as well of low level of antiamoebic antibodies. The multiple infections raise with the age and the predominant participation of helminths was demonstrated. PMID- 1914050 TI - Screening tests before surgery in children. PMID- 1914051 TI - Trigeminocardiac reflexes. PMID- 1914052 TI - Is preoperative haemoglobin testing justified in children undergoing minor elective surgery? AB - The need for preoperative haemoglobin determination before the administration of general anaesthesia to paediatric patients has long been an issue for debate. This study was undertaken to determine the value of routine preoperative haemoglobin testing in paediatric patients scheduled for minor surgery. Two thousand patients ages one month to 18 yr scheduled for minor surgery were studied. The patients were grouped according to age, Group I less than or equal to yr, Group II 1-5 yr, Group III greater than 5 yr. The charts of patients whose preoperative haemoglobin concentration (Hb) was less than 100 g.L-1 were reviewed at a later date to determine the course of their anaesthesia and surgery. Eleven patients, all of whom were greater than 5 yr (0.5%), had a Hb less than 100 g.L 1. Of these, three patients, 27%, had their surgery deferred, whereas the remaining eight patients, 73%, underwent anaesthesia and surgery without complications. The three patients who were deferred returned for uneventful anaesthesia and surgery following oral iron therapy. We conclude that healthy paediatric patients five years and older scheduled for minor surgery do not require routine Hb determinations. Furthermore, the low incidence of anaemia and low deferral rate of anaemic children, 1-5 yr of age, lead us to question the value of preoperative Hb testing in this age group. PMID- 1914053 TI - A comparison of propranolol and diazepam for preoperative anxiolysis. AB - The effectiveness of propranolol, a nonsedating anxiolytic premedication, was studied by monitoring preoperative anxiety and postoperative recovery of cognitive function in 92 healthy ASA physical status I females aged 15-42 yr undergoing outpatient dilatation and curettage (D&C) for therapeutic abortion. In a randomized double-blind design, patients received one of the following oral medications 1-1.5 hr preoperatively: (1) diazepam 10 mg (n = 31); (2) propranolol 80 mg (n = 31); (3) placebo (n = 30). Anxiety throughout the hospital stay was monitored using the State-Trait Anxiety Inventory (STAI). Postoperative cognitive recovery was assessed using the digit span and Trieger tests. STAI anxiety levels were recorded on admission to hospital, immediately before entering the operating room, and two hours postoperatively. There was no difference among the anxiolytic properties of the three medications and all three patient groups showed a significant decrease in anxiety levels after administration of the medication. Tests of cognitive function after anaesthesia showed the fastest return to baseline status in patients receiving propranolol, possibly because beta adrenergic blockade blunted the autonomic signs of light anaesthesia and less anaesthetic was administered. None of the study premedications was demonstrated to have an anxiolytic advantage, but propranolol did offer a faster return of cognitive function in the postoperative period. PMID- 1914054 TI - Continuous opioid infusions for neurosurgical procedures: a double-blind comparison of alfentanil and fentanyl. AB - The ability of continuous infusions of opioids to control hypertension at the end of neurosurgical procedures without compromising prompt emergence was studied in patients undergoing craniotomy for supratentorial tumours. Four infusion regimens were compared in a randomized double-blind fashion; three of alfentanil and one of fentanyl. Low-dose alfentanil was administered to nine patients (35.1 micrograms.kg-1 then a continuous infusion of 16.2 micrograms.kg-1.hr-1); mid dose alfentanil to eight patients (70.2 micrograms.kg-1 then 32.4 micrograms.kg 1.hr-1); high-dose alfentanil to eight patients (105.3 micrograms.kg-1 then 48.6 micrograms.kg-1.hr-1). Eight additional patients were given fentanyl (8.3 micrograms.kg-1 then 1.6 micrograms.kg-1.hr-1). Using published values for the pharmacokinetic variables of alfentanil and fentanyl, modelling predicted stable concentrations of 60, 120, 180 ng.ml-1 for the alfentanil infusion regimens respectively and 2 ng.ml-1 with the fentanyl regimen. Maintenance anaesthesia comprised the opioid infusion, 50% N2O in O2 and isoflurane titrated to control mean arterial pressure (MAP) within 20% of ward MAP. Isoflurane was discontinued after closure of the dura. Nitrous oxide was discontinued at the same time as reversal of neuromuscular blockade. The opioid infusion was discontinued with closure of the galea. A greater time-averaged isoflurane concentration was required to control MAP within the prescribed limits in the low alfentanil group (ANOVA; P less than 0.05). The PaCO2 at two, five and 30 min after extubation were not different among groups. The times from discontinuing N2O to eye opening and tracheal extubation were not different. The time to follow commands was longer in the low alfentanil group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914055 TI - Epidural nalbuphine for analgesia following caesarean delivery: dose-response and effect of local anaesthetic choice. AB - The analgesic profile of epidural nalbuphine for postoperative pain relief and the impact of local anaesthetic choice upon this profile was investigated in 58 patients undergoing elective Caesarean delivery under epidural anaesthesia. Patients were randomized to receive either lidocaine 2% with 1:200,000 epinephrine or 2-chloroprocaine 3% for perioperative anaesthesia, followed by either 10, 20, or 30 mg of epidural nalbuphine administered at the first complaint of postoperative discomfort. Postoperative analgesia was quantitated on a visual analogue (VAS) scale, and by the time from the epidural opioid injection until the first request for supplemental pain medication. The duration of analgesia after lidocaine anaesthesia followed by 10, 20 or 30 mg nalbuphine was 77 (53-127) min, 205 (110-269) min, and 185 (116-241), respectively (median, 95% confidence interval, P less than 0.01, 20 and 30 mg vs 10 mg). Following 2 chloroprocaine anaesthesia, VAS remained consistently elevated: the median duration of analgesia was only 30-40 min and did not differ among the three doses of nalbuphine. Side-effects consisted only of somnolence, and were noted only following lidocaine anaesthesia. Somnolence was observed in 0, 20% and 50% of those receiving 10 mg, 20 mg and 30 mg of nalbuphine respectively (NS). No evidence of respiratory depression was noted in any patient. It is concluded that 20 or 30 mg of epidural nalbuphine provides analgesia for only two to four hours following Caesarean delivery with lidocaine anaesthesia, but anaesthesia with 2 chloroprocaine resulted in minimal or no analgesia from this opioid. Nalbuphine appears to be a disappointing agent for epidural use after Caesarean delivery. PMID- 1914056 TI - Analgesic and pulmonary effects of continuous intercostal nerve block following thoracotomy. AB - This study examined the beneficial effects and potential systemic toxicity from continuous intercostal nerve block by repeated bolus injections of bupivacaine. In this double-blind, randomized study, 20 post-thoracotomy patients were assigned to receive four doses of either: 20 ml 0.5% bupivacaine with epinephrine 5 micrograms.ml-1 (bupivacaine group, n = 10), or 20 ml preservative-free saline (placebo group, n = 10) through two indwelling intercostal catheters every six hours. Patients receiving intercostal bupivacaine injections had greater decreases in visual analogue pain scores (VAS) (P less than 0.05) and lower 24 hr morphine requirements, 16.6 +/- 4.6 mg vs 35.8 +/- 7.2 mg, than patients in the placebo group (P less than 0.05). Higher post-injection values of forced expiratory volume in one second, forced vital capacity and peaked expiratory flow rate were also observed in the bupivacaine group (P less than 0.01). Repeated intercostal bupivacaine administration did lead to systemic accumulation, but the peak bupivacaine level after 400 mg was low at 1.2 +/- 0.2 microgram.ml-1. Thus, the technique of continuous intercostal nerve block described in this study is an effective treatment for the control of post-thoracotomy pain. PMID- 1914057 TI - Hypoxaemia in adults in the post-anaesthesia care unit. AB - Continuous pulse oximetry was performed on 173 adults after general anaesthesia for elective inpatient surgery, throughout their post-anaesthesia care unit (PACU) stay. Supplemental oxygen was administered for greater than or equal to 30 min after arrival and subsequently discontinued before discharge to the ward. The mean and minimum oxyhaemoglobin saturation (SpO2) after discontinuing oxygen were lower than those values achieved during oxygen administration and preoperatively (P less than 0.001). At least one hypoxaemic episode (SpO2 less than or equal to 90% for greater than or equal to 15 sec) occurred in 70 subjects (41%) and 45 of these had a moderate-severe episode (SpO2 greater than or equal to 90% for less than or equal to 2 min or SpO2 less than or equal to 85%). The hypoxaemic episodes began 20 +/- 20 min (range 1-100; median 15) after discontinuing supplemental oxygen. Cyanosis was detected in only four of the 70 patients who desaturated. Factors associated with hypoxaemia were: ASA physical status class; surgical duration greater than or equal to 90 min; and preoperative mean SpO2 less than 95%. Factors not associated with hypoxaemia were: age, sex, % ideal body weight, smoking history, preoperative minimum SpO2, premedication and type of surgery. In conclusion, after discontinuing supplemental oxygen in the PACU, hypoxaemia was common, difficult to detect clinically, and associated with ASA class, surgical duration and preoperative mean SpO2. PMID- 1914058 TI - The pharmacokinetic behaviour of opioids administered during cardiac surgery. AB - Cardiac surgery with hypothermic cardiopulmonary bypass (CPB) is among the most commonly performed operations in Canada today. The potential effects of hypothermia and CPB on the disposition of certain opioids are reviewed. Reasons for prolongation of the elimination half-time of the opioids used during cardiac surgery are explored. The roles that age, hypothermia, protein binding and drug sequestration may play in changing opioid pharmacokinetic behaviour are examined and suggestions for future research are made. PMID- 1914059 TI - Trigeminocardiac reflexes: maxillary and mandibular variants of the oculocardiac reflex. AB - Three case reports are presented to illustrate the existence and importance of reflex bradycardic responses that can occur during maxillofacial surgical procedures. All three patients were healthy young adults undergoing operations which did not include any manipulation of orbital structures. After the patients had been anaesthetized for some time and were haemodynamically stable, profound bradycardia or ventricular asystole occurred suddenly in response to manipulations of the bony structures of the maxilla or mandible, or dissection of, or traction on, the attached soft tissue structures. The parasympathetic supply to the face is carried in the trigeminal nerve. Alternative afferent pathways must exist via the maxillary and/or mandibular divisions, in addition to the commonly reported pathway via the ophthalmic division of the trigeminal nerve in the classic oculocardiac reflex. The efferent arc involves the vagus, regardless of which branch of the trigeminal nerve transmits the afferent impulses. All patients undergoing maxillofacial procedures should be monitored carefully for reflex bradycardia and ventricular asystole. PMID- 1914060 TI - Minitracheostomy in elective surgery of the larynx: an alternative to formal tracheostomy. AB - A patient scheduled for surgical removal of a giant polyp of the larynx, and in whom difficult orotracheal intubation was anticipated in the preoperative visit, was managed successfully with a minitracheostomy performed with a Mini-Trach II kit. The ventilation achieved was adequate throughout the procedure. Thus, conventional tracheostomy was avoided. PMID- 1914061 TI - Low-volume ulnar nerve block within the axillary sheath for the treatment of reflex sympathetic dystrophy. AB - A case is described of reflex sympathetic dystrophy (RSD) of the upper limb following cerebral arteriography via the subclavian artery. The pain started in the hand and forearm but, over several weeks, spread to involve the whole arm. After identifying the ulnar nerve in the axillary bundle with a stimulator, a series of small volume injections (bupivacaine 0.5% with epinephrine 2.5 ml and methyl-prednisolone 40 mg) was given. These relieved the pain and reversed the trophic changes of RSD. It is suggested that this approach is a useful alternative treatment in cases of RSD of the upper extremity. PMID- 1914063 TI - Pneumocephalus following attempted epidural anaesthesia. AB - This report describes iatrogenic pneumocephalus in an obstetrical patient following attempted epidural anaesthesia using the loss of resistance technique. On the fourth attempt at epidural injection, an apparent loss of resistance was identified and 5 ml air was injected. The patient complained immediately of severe bifrontal headache followed by emesis. The baby was eventually delivered by Caesarean section, with general anaesthesia and avoiding nitrous oxide. The patient's headache resolved within 24 hr without further sequelae. PMID- 1914062 TI - Horner's syndrome and trigeminal nerve palsy following epidural anaesthesia for obstetrics. AB - While Horner's syndrome is a rare but occasionally reported side-effect of epidural block administered for labour, trigeminal nerve palsy has been described only once. The cases described in this report confirmed the benign nature of these neurological complications of epidurally administered anaesthetics which were not detrimental to fetal viability. The complications may be attributed to extensive cephalad spread of local anaesthetic, sometimes via unexplained routes and with surprisingly selective targeting effect (unilateral trigeminal nerve palsy). The atypical and unusually high cephalad spread of local anaesthetic in pregnant women at term is believed to be due to pregnancy-related altered anatomy and physiology of the epidural space. PMID- 1914064 TI - The anaesthetic management of a patient with a phaeochromocytoma and acute stroke. AB - A case is reported of a young woman in whom the diagnosis of a phaeochromocytoma was made after a major stroke. Preoperative preparation included the introduction of phenoxybenzamine, 10 mg.day-1, and propranolol, 80 mg.day-1, over a two-week period. The presence of cerebrovascular disease and the marked orthostatic changes in blood pressure and heart rate to low-dose phenoxybenzamine prevented the establishment of full alpha blockade. Incomplete alpha blockade probably contributed to the hypertensive response to manipulation of the tumour (220/150 mmHg) and hypotension occurred after removal of the tumour (80/45 mmHg). An anaesthetic technique was chosen to provide haemodynamic stability as well as protection against cerebral ischaemia. Invasive haemodynamic monitoring, a four channel processed electroencephalograph and somatosensory evoked potentials were used to accomplish these goals. PMID- 1914065 TI - Anaesthetic management of phaeochromocytoma associated with tricuspid atresia. AB - The anaesthetic management of a patient with phaeochromocytoma, tricuspid atresia and pulmonary vascular stenosis is reported. The patient received no preoperative preparation with adrenergic blockers. Anaesthesia was induced and maintained with fentanyl, diazepam and sevoflurane. Intraoperative blood pressure was controlled with sodium nitroprusside, sevoflurane, phentolamine, and propranolol. For hypotension after resection of the tumour norepinephrine was required. This patient did not have a systemic to pulmonary shunt procedure performed, so the maintenance of pulmonary blood flow in the presence of haemodynamic instability during operation for phaeochromocytoma was a major concern. Monitoring of oxyhaemoglobin saturation (SpO2) with a pulse oximeter was considered to be useful because SpO2 may reflect pulmonary flow. During serious haemodynamic disturbances due to the manipulation of the tumour, the heart rate was inversely correlated with SpO2, but the relationship between mean arterial pressure and SpO2 was weak. Therefore, control of heart rate appeared to be more important than control of blood pressure in this case. PMID- 1914066 TI - Elective oral tracheal intubation in cervical spine-injured adults. AB - There is controversy regarding the optimal mode of elective tracheal intubation in the patient with an unstable cervical spine following trauma. A ten-year review of 150 patients with traumatic cervical spine injuries with well-preserved neurological function, presenting for operative stabilization, was conducted to compare neurological outcome with the mode of tracheal intubation. Preoperative neurological deficits were identified in 49 patients (33%); most were single level radiculopathies. Intubation occurred after induction of general anaesthesia in 83 patients (55%) and in 67 patients (45%) the tracheas were intubated with the patient awake. One hundred and six patients (71%) underwent oral tracheal intubation and 44 underwent nasal tracheal intubation. Ten intubations were deemed to be difficult requiring more than one attempt to effect intubation. Cervical spine immobilization during intubation was documented in 86 patients (57%). Weighted traction or manual in-line traction were the two manoeuvres most commonly employed to maintain spinal alignment during intubation. After surgery, two patients had new neurological deficits. There were no differences in neurological outcome whether intubation was performed while the patient was awake or under general anaesthesia, or comparing oral tracheal intubation with all other techniques (P = 0.5, Fisher exact test). Also, in-line traction did not affect neurological outcome. Oral tracheal intubation with in-line stabilization, either performed after induction of general anaesthesia or with the patient awake, remains an excellent option for elective airway management in patients with cervical spine injuries. PMID- 1914067 TI - Systemic lupus erythematosus and the obstetrical patient--implications for the anaesthetist. AB - Systemic lupus erythematosus (SLE) is a multisystem, chronic inflammatory disease characterized by autoantibody production. The disease is most frequently found in women of childbearing age and therefore may co-exist with pregnancy. The clinical manifestations of the disease are variable and depend on the severity of damage to organ systems such as musculoskeletal, renal, haematological, neurological, cardiac, and respiratory. Many patients require drugs such as aspirin or prednisone. The pregnant patient may experience exacerbations of the disease, neonatal loss, and obstetrical complications such as pre-eclampsia. Patients with the Lupus Anticoagulant are at risk for an abnormal perinatal course. The anaesthetic management will depend on the patient's clinical status and the well being of the fetus. The patient should be examined to determine the extent of end organ damage, current medications, and the health of the fetus. Laboratory investigations such as a coagulation screen and tests of renal function should be performed before anaesthetic intervention if time permits. A multidisciplinary approach to care of the patient and resources to manage complications are essential to optimize the outcome for both mother and newborn. PMID- 1914068 TI - Arterial oxygen saturation in cigarette smokers following general anaesthesia. PMID- 1914069 TI - Nasotracheal intubation using Bullard laryngoscope. PMID- 1914070 TI - Intravenous infusions and one-way valves. PMID- 1914071 TI - Emergence phenomena after ketamine anaesthesia: the influence of music. PMID- 1914072 TI - Adhesion mechanisms in lymphatic metastasis. AB - The role of cellular adhesion in regional lymph node metastasis of solid tumors has been investigated. The data reviewed is based on studies in four different tumor models of human, rat and murine origin. An in vitro assay measuring tumor cell attachment to cryostat sections of normal peripheral lymph nodes, obtained from the species of tumor origin was used to compare the adhesion of tumor sublines with different metastatic potentials. A good correlation was found between tumor cell potential to metastasize to regional nodes and the adhesion to the sections in all models studied. The adhesion of all tumor lines could be blocked by Arg-Gly-Asp containing peptides while pretreatment of the cells with antibodies to integrins implicated beta 1 and beta 3 receptor complexes in the adhesion. Ligand binding assays provided indirect evidence that the preferential attachment of the metastatic tumor lines to the frozen sections was mediated via extracellular matrix proteins such as fibronectin, vitronectin and type IV collagen. As these basement membrane proteins have been localized to the outer surfaces of reticular fibers which are known to permeate the lymph node and trasverse the subcapsular sinus it is postulated that tumor cell attachment to these fibers may facilitate and possibly be required for tumor cell retention and growth in the invaded regional nodes. PMID- 1914073 TI - PMN adhesion and extravasation as a paradigm for tumor cell dissemination. AB - Current evidence indicates that the localization and extravasation of neutrophils is a complex process involving several adhesion molecules with apparently distinct functions, and a highly coordinated and dynamic interplay between the neutrophil and the endothelial cell that is influenced by the shear forces present at the interface between these two cell types. Chemotactic stimulation of the neutrophil not only induces directed locomotion but markedly alters the surface expression and functions of the neutrophil adhesion molecules, having both an upregulating and downregulating influence. Cytokines such as interleukin 1 induce the synthesis and surface expression of endothelial adhesion molecules such as ICAM-1 and ELAM-1, and stimuli such as thrombin and histamine induce the rapid mobilization to the endothelial surface of another adhesion molecule, GMP 140. Transendothelial migration of neutrophils in most settings both in vitro and in vivo appears to require CD18 integrins on the neutrophil and ICAM-1 on the endothelial cells. This is most clearly demonstrated by the genetic deficiency of CD18 in humans, dogs and cattle, where neutrophil extravasation at most inflammatory sites is almost completely absent. Though the coordinated functions of the various neutrophil and endothelial adhesion molecules are highly efficient in promoting neutrophil extravasation, there has been relatively little investigation of their utilization in tumor cell dissemination. Recent results indicate that such studies may prove fruitful. For example, some adenocarcinoma cell lines express the complex carbohydrate (sialyl Lewis x) recently shown to be a ligand for ELAM-1. PMID- 1914075 TI - The pharmacokinetics of the quinazoline antifolate ICI D 1694 in mice and rats. AB - N-(5-[N-(3,4-Dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N- methylamino]-2 thenoyl)-L-glutamic acid (ICI D1694) is an analogue of the thymidylate synthase inhibitor N10-propargyl-5,8-dideazafolic acid (CB3717). CB3717 was found to be an active anticancer agent in early clinical studies, but its use was limited by its relative insolubility at physiological pH. ICI D1694 has been shown to be a more active anticancer agent than CB3717 in model systems, and it is devoid of the acute renal toxicity associated with the administration of the latter drug to mice. In the present study, the pharmacokinetics of ICI D1694 were studied in both mice and rats using reverse-phase HPLC. In rats, ICI D1694 clearance (CL) conformed to a two-compartment open model and was rapid (CL = 10.7 ml min-1 kg-1, t1/2 beta = 30 min). Excretion was mainly biliary (65% of the delivered dose in 4 h vs 12% in urine) in the rat following a 100-mg/kg i.v. bolus. A high degree of protein binding was seen in rat plasma (greater than or equal to 90% over the range of 20-100 microM). In mice, ICI D1694 CL = 27 ml min-1 kg-1 and t1/2 beta = 30 min following 100 mg/kg i.v., which was significantly faster than CB3717 clearance (CL = 6 ml min-1 kg-1, t1/2 beta = 93 min). ICI D1694 was fully bioavailable following i.p. administration (AUC = 3.73 mg ml-1 min i.v. 4.03 mg ml-1 min i.p.), but its bioavailability following oral administration appeared to be low (approximately 10%-20%). Tissue distribution and excretion studies in mice suggested that biliary excretion predominated, confirming the results obtained in rats. Following an i.v. dose of 500 mg/kg ICI D1694 in mice, drug was detectable at 24 h, suggesting the presence of a third phase of plasma clearance. The initial HPLC assay could not detect this third phase following a dose of 100 mg/kg; hence, a more sensitive assay was developed that includes a solid-phase extraction step. The latter assay was used to define the third phase of ICI D1694 clearance in mice, and preliminary studies demonstrated a terminal half-life of 6.5 +/- 2.7 h. PMID- 1914074 TI - Chemotherapy in malignant mesothelioma: a review. AB - This review of malignant mesothelioma focuses on the activity of single-agent and combination chemotherapy, a field in which research has thus far been rather unsystematic and sparse. Available results neither accede to any substantial drug activity nor justify the use of standard therapy. Furthermore, even when pooled most findings do not fulfil the basic criteria for a phase II trial. Prospective (multicenter) phase II trials are recommended for the identification of new agents that show antineoplastic activity in malignant mesothelioma. The use of computed tomography scans can assist in the prediction of the extent of disease both before and during treatment. Tumor-biological systems using mice xenografts or cell lines of human mesothelioma should be further developed so as to improve the screening of new agents exhibiting potential antineoplastic activity that is especially directed against mesothelioma. PMID- 1914076 TI - Antiproliferative activity of purine nucleoside dialdehydes against leukemia L1210 in vitro. AB - Sixteen purine nucleoside dialdehydes were assayed for antiproliferative activity against murine leukemia L1210 grown in vitro. These compounds either lacked the terminal hydroxymethyl group that is necessary in most cases for phosphorylation, and/or had stereochemically different configurations at one or two positions, or had some alteration in the purine ring structure. Among the latter were two lipophilic N6-benzyladenine containing dialdehydes, and two nucleoside dialdehydes with a bromine atom at C-8 of the purine. These nucleoside dialdehydes, unlike most clinically useful anticancer nucleosides, did not require enzymatic phosphorylation to become activated. The most interesting agent in this group of compounds was the lipophilic nucleoside dialdehyde obtained from N6-benzyladenosine after periodate oxidation. It had an IC50 of 1.0 +/- 0.2 microM, and appears to function by limiting the formation of deoxyguanosine diphosphate (dGDP) by inhibition of ribonucleoside diphosphate reductase, the rate limiting step in the biosynthesis of deoxyribonucleotides. PMID- 1914078 TI - Antitumor activity on murine tumors of a novel antitumor benzoylphenylurea derivative, HO-221. AB - A novel antitumor compound, N-[4-(5-bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2 nitrobenzoyl ) urea (HO-221) was evaluated for its antitumor activity in experimental tumor models. HO-221 preparation was given orally to tumor-bearing animals. The compound exhibited significant effects against various tumors such as P388 and L1210 leukemias; M5076 reticulum-cell sarcoma; colon 38 carcinoma; human xenografts MX-1, LX-1, GA-1, and Co-1; Lewis lung carcinoma; sarcoma 180; and Walker 256 carcinosarcoma and was especially effective against solid tumors. However, its effect on murine B16 melanoma was moderate. Intermittent administration of HO-221 produced better results. The effects of HO-221 on human tumor xenografts were compared with those of other antitumor agents. HO-221 showed activity against LX-1 lung and Co-1 gastrointestinal tumor and was also effective against advanced-stage L1210 leukemia and Lewis lung carcinoma. Furthermore, the effect of HO-221 on drug-resistant tumors was examined using murine leukemias L1210 and P388. It showed no cross-resistance with the known antitumor agents Adriamycin (ADM), daunomycin (DM), vincristine (VCR), mitomycin C (MMC), cisplatin (CDDP), 5-fluorouracil (5-FU), cytosine arabinoside (Ara-C), methotrexate (MTX), cyclophosphamide (CPA), or carboquone (CQ), and collateral sensitivity to HO-221 was found in MMC-, CDDP-, and CPA-resistant sublines. HO 221 exhibits significant reproducible, broad-spectrum antitumor activity against experimental tumors as well as human neoplasms. PMID- 1914077 TI - Production of hydrogen peroxide by cutaneous T-cell lymphoma following photopheresis with psoralens and ultraviolet light. AB - Treatment of peripheral blood mononuclear cells with 8-methoxypsoralen (8-MOP) and ultraviolet light, a procedure known as PUVA, has been found to be useful in the management of systemically disseminated cutaneous T-cell lymphoma (CTCL). In the present study we used a highly sensitive flow cytometric assay in conjunction with the hydroperoxide-sensitive dye 2',7'-dichlorofluorescein diacetate to measure intracellular hydrogen peroxide in normal lymphocytes and CTCL following PUVA treatment. Based on their laser light-scattering properties, lymphocytes were separated into three major subpopulations. We found that ultraviolet light alone caused an increase in the hydrogen peroxide content of each of the subpopulations, a response that was augmented when the cells were pretreated with 8-MOP (50 ng/ml). Cells from CTCL patients were more sensitive to the effects of 8-MOP than were normal lymphocytes. In both cell types, the production of hydrogen peroxide was found to be inhibitable by catalase. We noted an increase in hydrogen peroxide production following photopheresis; however, this was observed only 24 h after treatment. In addition, a further increase in hydrogen peroxide production was observed in lymphocytes isolated from peripheral blood that had been obtained from patients at 15 min after a second photopheresis treatment. Hydrogen peroxide is known to modulate the action of cytokines as well as the immunological responses of leukocytes. Our data suggest that the production of hydrogen peroxide by lymphocytes may be important in the action of PUVA in CTCL. PMID- 1914079 TI - Accumulation of estramustine and estromustine in adipose tissue of rats and humans. AB - The tissue distribution of estramustine and estromustine, two cytotoxic lipophilic metabolites of estramustine phosphate (Estracyt, EMP) was studied in rats and humans. A single dose of [3H]-estramustine was given i.v. to groups of rats. At 24 h after administration, the concentration of radioactivity in fat was about 20, 12, and 2 times that in muscle, plasma, and liver, respectively. Liquid chromatography verified that the radioactivity represented estramustine and estromustine. The clinical relevance of these results was investigated in pancreas cancer patients treated with a single oral dose of Estracyt at 12-16 h before surgery. As judged by gas chromatography, the concentration of estromustine, which is the main metabolite in man, was about 13 times higher in fat than in plasma and was also higher in adipose tissue than in muscle and liver. After 5 days of Estracyt treatment, the adipose uptake of estromustine was even higher, namely, about 40 times that in plasma and 8 times that in muscle and liver. Thus, our results demonstrate that estramustine and estromustine are stored in adipose tissue after the administration of EMP; this is important for the pharmacokinetics and, consequently for the therapeutic effects of Estracyt. PMID- 1914080 TI - Prevention of doxorubicin-induced cardiomyopathy by reduced glutathione. AB - The aim of the present investigation was to evaluate the potential cardioprotective effect of reduced glutathione (GSH) against the delayed cardiomyopathy induced by doxorubicin (DXR) in a well-documented rat model. DXR was administered i.v. at a weekly dose of 3 mg/kg for a total of 4 doses; 250 or 500 mg/kg of GSH was given i.v. 10 min before and 2 h after each DXR injection, resulting in a total weekly dose of 500 or 1000 mg/kg, respectively. The development of cardiotoxicity was monitored in vivo by means of electrocardiography (QaT duration), and was evaluated by measuring the contractile performance of isolated atria and by light and electron microscopy of left ventricular samples excised 5 weeks after the last DXR administration. DXR was found to impair body weight gain and to produce an irreversible and time dependent prolongation of QaT, a decrease in myocardial contractility of isolated atria and typical morphologic alterations, including myocyte vacuolization and myofibrillar loss. Pretreatment with GSH at a dose of 500 mg/kg x 2, but not at 250 mg/kg x 2, partially prevented the impairment of body weight gain, QaT prolongation in ECG and the decrease in myocardial contractility of isolated atria induced by DXR. Alterations of the morphologic pattern were also significantly reduced in animals receiving the higher dose of GSH. Determinations of the cardiac non-protein sulfhydryl group content showed that GSH, at doses higher than or equal to 500 mg/kg, significantly increased this parameter, irrespective of the presence of DXR. In conclusion, the present data indirectly support the hypothesis that oxidative damage is involved in DXR cardiotoxicity and indicate that maintenance of the reduced thiol pool could be an important issue in myocardial protection. PMID- 1914081 TI - Synergistic cytotoxic actions of cisplatin and liposomal valinomycin on human ovarian carcinoma cells. AB - We have previously shown that the toxicity of valinomycin (VM), a membrane-active agent with antineoplastic activity, can be dramatically reduced with no loss of the antitumor efficacy of the drug by incorporating it into liposomes. In the present study, we investigated the interaction between cis diamminedichloroplatinum(II) (CDDP) and VM in terms of in vitro cytotoxicity to human ovarian tumor cells. Using the MTT assay and analyzing the data using the median-effect principle, we showed that synergistic cytotoxic interactions exist between CDDP and VM in their liposomal form. The degree of cytotoxic synergism was influenced by the duration of drug exposure and the dose ratio. The cellular accumulation of platinum by ovarian cells at 37 degrees C was slightly higher after exposure to VM as compared with controls; however, it is not clear that this accounts for the cytotoxic synergism. These results suggest that the combination of liposomal VM and CDDP may have merit as a form of localized drug delivery for the treatment of ovarian cancer disseminated within the peritoneal space. PMID- 1914082 TI - Inhibition of 7-hydroxymethotrexate formation by amsacrine. AB - The inhibition of methotrexate (MTX) biotransformation to 7-hydroxymethotrexate (7-OH-MTX) by 4'-(9-acridinylamino)-methanesulfon-m-anisidide (mAMSA) was studied in bile-drained rats in vivo and in incubates of isolated rat hepatocytes and rat liver homogenate in vitro. In vivo, i.v. administration of 10 mg/kg mAMSA prior to [3H]-MTX infusion (50 mg/kg) led to a significant alteration in 7-OH-MTX kinetics. 7-OH-MTX peak concentrations and AUC in bile and serum were reduced by 75% and the recovery of MTX as 7-OH-MTX in bile and urine decreased by 70%, whereas MTX pharmacokinetics remained unaltered. In suspensions of isolated hepatocytes, 10 microM mAMSA led to a 54% decrease in 7-OH-MTX formation. However, the hepatocellular influx and efflux of MTX was not perturbed by mAMSA. Preincubation of rat-liver homogenates with 1.25-10 microM mAMSA reduced the formation of 7-OH-MTX by up to 73%. mAMSA appeared to inhibit MTX hydroxylation competitively, exhibiting a Ki of 3 microM. Due to its inhibition of the MTX oxidizing system, mAMSA may be beneficial in combination chemotherapy with MTX by reducing 7-OH-MTX-associated toxicity and, possibly, enhancing the cytotoxic effects of MTX. PMID- 1914083 TI - Antitumor effects of ketoconazole and trifluoperazine in murine T-cell lymphomas. AB - In vitro and in vivo antitumor effects of ketoconazole (KTZ), trifluoperazine (TFP), and combinations of both drugs were examined in cell lines established from radiation leukemia virus (RadLV)-induced T-cell lymphomas. KTZ inhibited [3H]-thymidine incorporation in the tumor cells in vitro; 50% inhibition of DNA synthesis was observed at concentrations of 4-7 micrograms/ml. [3H]-thymidine uptake in bone-marrow and spleen cells prepared from healthy mice was also inhibited by KTZ, but 50% inhibition was observed only at a concentration of 50 micrograms/ml. Stimulation of spleen cells with concanavalin A led to an increase in their sensitivity to the inhibition of DNA synthesis by KTZ. The tumor-cell lines varied in their sensitivity to the inhibition of DNA synthesis by TFP, and the effects of TFP on DNA synthesis in bone-marrow and spleen cells were similar to those observed in the tumor cells. Synergistic, additive, or less than additive effects of the drug combinations on the inhibition of DNA synthesis in vitro were observed both in tumor cells and in bone-marrow cells. In vivo experiments were conducted on groups of C57BL/6 (B6) mice that were inoculated s.c. with tumor cells and then treated with i.p. injections of KTZ, TFP or both. Control groups were injected with phosphate-buffered saline (PBS). Each of the drugs alone as well as their combinations caused a significant delay in the appearance of palpable tumors, a decrease in tumor size, and a marked prolongation of survival. The concentrations of the drugs used in in vivo experiments did not affect the WBC counts in the peripheral blood of healthy mice. KTZ is currently used for the treatment of prostatic cancer because of its inhibitory effect on testosterone biosynthesis. The results of the present study indicate the hormone-independent chemotherapeutic potential of KTZ, TFP, and combinations of the two drugs. PMID- 1914084 TI - Phase II trial of carboplatin or iproplatin in cervical cancer. AB - From July 1984 to November 1987, 89 patients with recurrent measurable squamous cell cancer of the uterine cervix were randomized in a single institution to receive treatment with either carboplatin (CBDCA) or iproplatin (CHIP). Objective response rates were similar: 2 complete regressions (CRs) and 10 partial regressions (PRs) were recorded both in the 46 evaluable patients treated with CBDCA (response rate, 26.1%; 95% confidence interval, 15-41%) and in the 40 evaluable patients treated with CHIP (response rate, 30%; 95% confidence interval, 17-47%). The median duration of response was 5.5 months for CBDCA and 6 months for CHIP; the median survival was 7.5 and 7.6 months, respectively. Both drugs were given in an outpatient setting and myelosuppression (thrombocytopenia) was the predominant toxicity. Analysis of all toxic events yielded additional interesting observations: the occurrence of moderate to severe platelet nadirs beyond cycle 1 was confined to CHIP, a higher incidence of gastrointestinal toxicity during treatment with CHIP, and five moderate to severe complaints of asthenia (recorded as neurologic events) during CHIP therapy versus only one during treatment with CBDCA. Because of its antitumor activity and its toxicologic advantage, a future role for CBDCA in the treatment of cervical cancer appears likely. PMID- 1914085 TI - Dose-toxicity relationship of carboplatin in combination with cyclophosphamide in ovarian cancer patients. AB - A study was undertaken to examine the relationships between carboplatin's pharmacokinetic parameters and the myelotoxicity associated with its administration in combination with cyclophosphamide. An additional aim of the study was to test the applicability of the method proposed by Calvert et al. for calculation of the carboplatin dose to be used in the combination regimen. A total of 24 previously untreated ovarian cancer patients were given a combination of 250-500 mg/m2 carboplatin and 500 mg/m2 cyclophosphamide every 4 weeks for 4 months. The pharmacokinetics of carboplatin and the associated myelotoxicity were investigated in 64 courses. The results showed a significant correlation (r = 0.89) between the AUC calculated for carboplatin and that predicted according to Calvert's formula [carboplatin dose in milligrams = AUC (glomerular filtration rate +25)]. We conclude that the model is a useful guide in the calculation of the carboplatin dose to be given in combination with cyclophosphamide, and it enables a more precise prediction of the carboplatin exposure than does the conventional calculation, which is based on milligrams of drug per square meter of body surface. The AUC for carboplatin was a reliable predictor of the myelotoxicity as measured by the relative decrease in thrombocyte count. However, the relationship between AUC and myelotoxicity changed during the treatment because of increasing bone marrow toxicity. Despite this finding, dose calculation based on carboplatin's AUC appears to provide an improvement in the clinical use of the drug, and the method also seems to be fully applicable in combination chemotherapy with cyclophosphamide. PMID- 1914087 TI - Pica and iron-deficiency anaemia. AB - In two cases of children with pica referred to a child psychiatrist, both were found to have undiagnosed iron-deficiency anaemia. Treatment with iron supplements and dietary advice led to decrease or cessation of pica. PMID- 1914086 TI - Mitozantrone and prednimustine in the treatment of advanced breast cancer--a toxic regimen with low activity. AB - The combination of mitozantrone and prednimustine has been reported to elicit response rates of around 50% in patients with advanced breast cancer. In the present trial, either three or nine courses of this combination were given to previously untreated patients with advanced breast cancer. Mitozantrone was given at 12 mg/m2 on day 1 and prednimustine was given orally at 130 mg/m2 on days 1-5; treatment was repeated every 4 weeks. A total of 34 patients were treated; the performance status was 0-1 in 29 subjects and 2 in 5 cases. Locoregional disease only was present in 13 patients; 9 showed lung involvement; 8, liver; 3, bone; and 1, stomach involvement. A total of 10 subjects had received no prior hormone therapy. The median disease-free interval from the time of initial diagnosis was 24 months (range, 0-144 months). In all 14/23 patients exhibited an oestrogen receptor level of greater than 20 fmol. Grade 1 nausea and vomiting occurred in 16 patients and that of grade 2-3, in 11 subjects; nausea was prolonged for greater than 10 days in 7 cases. Grade 4 neutropenia occurred in 2 patients. The response rate was 21% (95% confidence interval, 8%-38%). The combination of mitozantrone and oral prednimustine is toxic and displays low activity. PMID- 1914088 TI - A psychiatric residential centre for children and adolescents: a pilot study of its patients' characteristics and improvement while resident. AB - This paper describes the history and philosophy of a unique residential treatment unit in Ireland which caters for emotionally and behaviourally disturbed children and adolescents. A pilot study was undertaken to help identify the type of patient seen and who benefited from the treatment. PMID- 1914089 TI - Atrial contribution to ventricular filling in mitral stenosis. AB - BACKGROUND: The importance of the contribution of atrial systole to ventricular filling in mitral stenosis is controversial. The cause of reduced cardiac output following the onset of atrial fibrillation may be due to an increased heart rate, a loss of booster pump function, or both. METHODS AND RESULTS: We studied the atrial contribution to filling under a variety of conditions by combining noninvasive studies of patients with computer modeling. Thirty patients in sinus rhythm with mild-to-severe stenosis were studied with two-dimensional and Doppler echocardiography for measurement of mitral flow velocity and mitral valve area (MVA). The mean +/- SD atrial contribution to left ventricular filling volume was 18 +/- 10% and varied inversely with mitral resistance. Patients with mild mitral stenosis (MVA, 1.8 +/- 0.7 cm2) and severe mitral stenosis (MVA, 0.9 +/- 0.2 cm2) had atrial contributions of 29 +/- 4% and 9 +/- 5%, respectively. The pathophysiological mechanisms responsible for these trends were further investigated by the computer model. In modeled severe mitral stenosis, increasing heart rate from 75 to 150 beats/min caused an increase of 5.2 mm Hg in mean left atrial pressure, whereas loss of atrial contraction at a heart rate of 150 beats/min caused only a 1.3 mm Hg increase. CONCLUSIONS: The atrial booster pump contributes less to ventricular filling in mitral stenosis than in the normal heart, and the loss of atrial pump function is less important than the effect of increasing heart rate as the cause of decompensation during atrial fibrillation. PMID- 1914090 TI - A new method for quantitation of mitral regurgitation based on color flow Doppler imaging of flow convergence proximal to regurgitant orifice. AB - BACKGROUND: Imaging of the flow convergence region (FCR) proximal to a regurgitant orifice has been shown to provide a method for quantifying the regurgitant flow rate. According to the continuity principle, the FCR is constituted by concentric hemispheric isovelocity surfaces centered at the orifice. The flow rate is constant across all isovelocity surfaces and equals the flow rate through the orifice. For any isovelocity surface the flow rate (Q) is given by: Q = 2 pi r2 Vr, where 2 pi r2 is the area of the hemisphere and Vr is the velocity at the radial distance (r) from the orifice. METHODS AND RESULTS: We studied 52 consecutive patients with mitral regurgitation (mean age, 49 years; age range, 21-66 years) verified by left ventricular angiography using color flow mapping. The FCR r was measured as the distance between the first aliasing limit- at a Nyquist limit obtained by zero-shifting the velocity cutoff to 38 cm/sec- and the regurgitant orifice. Seven patients without evidence of an FCR had only grade 1+ mitral regurgitation angiographically. There was a significant relation between the Doppler-derived maximal instantaneous regurgitant flow rate and the angiographic degree of mitral regurgitation in the other patients (rs = 0.91, p less than 0.001). The regurgitant flow rate by Doppler also correlated with the angiographic regurgitant volume (r = 0.93, SEE = 123 ml/sec) in the 15 patients in normal sinus rhythm and without other regurgitant lesions in whom it could be measured. The correlation between regurgitant jet area within the left atrium and the angiographic grade was only fair (rs = 0.75, p less than 0.001). CONCLUSIONS: Color flow Doppler provides new velocity information about the proximal FCR in patients with mitral regurgitation. According to the continuity principle, the maximal instantaneous regurgitant flow rate, obtained with the FCR method, may provide a quantitative estimate of the severity of mitral regurgitation, which is relatively independent of technical factors. PMID- 1914091 TI - Muscle carnitine deficiency in patients with severe peripheral vascular disease. AB - BACKGROUND: This study was designed to evaluate the effect of severe peripheral arterial insufficiency on carnitine concentrations and carnitine acetyltransferase and palmitoyltransferase activities in the ischemic skeletal muscles of patients with severe peripheral vascular disease. METHODS AND RESULTS: Nine biopsy specimens of ischemic muscles were obtained from five patients undergoing reconstructive vascular surgery. Biopsies from 35 normal subjects served as controls. Ischemic muscles showed a significant reduction in total carnitine from the control value of 20.9 +/- 5.2 to 11.6 +/- 6.2 nmol/mg noncollagen protein (p less than 0.01). A significantly lower free carnitine and acylcarnitine content contributed to this reduction. Similarly, carnitine acetyltransferase activity was reduced in the ischemic muscles from the control value of 102.1 +/- 41.2 to 52.9 +/- 22.1 nmol/min/mg noncollagen protein (p less than 0.01). On the contrary, carnitine palmitoyltransferase activity did not show any change (0.29 +/- 0.05 nmol/min/mg noncollagen protein in the ischemic muscles and 0.28 +/- 0.07 nmol/min/mg noncollagen protein in controls). Carnitine, acylcarnitines, and enzyme activities were also measured in the ischemic muscles in four additional patients 2 days after intravenous administration of L propionylcarnitine (1.5 g as a single bolus followed by an infusion of 1 mg/kg/min for 30 minutes). Treatment restored normal levels of carnitine and its esters in the ischemic muscles but did not affect enzyme activities. CONCLUSIONS: Demonstration of carnitine deficiency in severe peripheral vascular disease substantiates previous findings showing the efficacy of carnitine supplementation to ischemic muscles. Furthermore, the feasibility of restoring carnitine homeostasis with L-propionylcarnitine provides the basis for clinical trials aimed at assessing the efficacy of this carnitine ester in the treatment of peripheral vascular disease. PMID- 1914092 TI - Left ventricular regional relaxation and its nonuniformity in hypertrophic nonobstructive cardiomyopathy. AB - BACKGROUND: Regional nonuniformity has been suggested to be closely related to left ventricular (LV) relaxation in diseased heart. The purpose of the present study was to assess LV global and regional relaxation in patients with nonobstructive hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Left ventriculography was conducted simultaneously with pressure micromanometry in 10 normal control subjects and 11 patients with nonobstructive HCM. LV silhouettes in the right anterior oblique projection were divided into eight regions, and regional wall stress during isovolumic relaxation was computed for six regions from the midventricle to the apex. In HCM patients, isovolumic relaxation time (IRT) and the time constant of LV pressure decrease (Tp) were greater than in control subjects (IRT, 84 +/- 13 versus 66 +/- 6 msec; Tp, 51 +/- 8 versus 36 +/- 5 msec, respectively; p less than 0.01). In HCM patients, the (-)dP/dt upstroke pattern was convex-downward, and dP/dt(20/60), the ratio of dP/dt values 20 and 60 msec after peak (-)dP/dt, was less than in control subjects (1.46 +/- 0.16 versus 2.15 +/- 0.14, p less than 0.01). These findings suggest that there is impaired LV relaxation in HCM patients. End-systolic regional wall stress was lower, and the time constant of regional stress decrease (Tst) was prolonged for each region in HCM patients compared with control subjects. In the HCM group, Tst tended to be more prolonged in regions with increased wall thickness than in regions with normal wall thickness (60 +/- 15 versus 50 +/- 11 msec, p less than 0.01). The coefficient of variation for Tst values in six areas of the left ventricle was calculated in each subject and was greater in HCM patients than in control subjects (13 +/- 7% versus 7 +/- 3%, p less than 0.05), indicating regional nonuniformity in Tst during isovolumic relaxation in HCM patients. CONCLUSIONS: Significant correlations existed between the coefficients of variation for Tst and Tp (r = 0.80, p less than 0.01), IRT (r = 0.79, p less than 0.01), and dP/dt(20/60) (r = -0.67, p less than 0.05) in the HCM group. Thus, regional nonuniformity is closely related to the impairment of LV relaxation in HCM. PMID- 1914093 TI - QT interval prolongation predicts cardiovascular mortality in an apparently healthy population. AB - BACKGROUND: In myocardial infarction patients, heart rate-adjusted QT interval (QTc), an electrocardiographic indicator of sympathetic balance, is prognostic for survival. METHODS AND RESULTS: In a 28-year follow-up, the association between QTc and all-cause, cardiovascular, and ischemic heart disease mortality was studied in a population of 3,091 apparently healthy Dutch civil servants and their spouses, aged 40-65 years, who participated in a medical examination during 1953-1954. Moderate (QTc, 420-440 msec) and extensive (QTc, more than 440 msec) QTc prolongations significantly predict all-cause mortality during the first 15 years among men (adjusted respective relative risks [RRs], 1.5 and 1.7) and among women (RRs, 1.7 and 1.6). In men, cardiovascular (RRs, 1.6 and 1.8) and ischemic heart disease mortality (RRs, 1.8 and 2.1) mainly account for this association. In women, the association cannot be attributed specifically to cardiovascular and ischemic heart disease mortality. RRs for a subpopulation without any sign of heart disease at baseline are similar. The same is observed for QTc prolongation after light exercise, although in this situation most associations are not statistically significant, probably because of smaller numbers in the QTc prolongation categories. CONCLUSIONS: Our results suggest that QTc contributes independently to cardiovascular risk. If autonomic imbalance is an important mechanism, it might be speculated that changes in life-style (e.g., with regard to physical exercise and smoking) may have a preventive impact. PMID- 1914094 TI - Efficacy of permanent pacing in the management of high-risk patients with long QT syndrome. AB - BACKGROUND: From the international long QT syndrome (LQTS) study, 30 patients with corrected QT interval (QTc) of more than 0.44 second 1/2 were identified who had permanent pacemakers implanted for management of recurrent syncope or aborted cardiac arrest. METHODS AND RESULTS: Pacemakers were implanted on average 7 years after the onset of the first syncopal episode. Most of the patients were female (87%), the average age at implantation was 19 +/- 13 years, the mean QTc was 0.55 +/- 0.08 second, and 57% were receiving antiadrenergic treatment for LQTS when the pacemaker was placed. Using birth as the time origin, the median cardiac event rate was significantly (p less than 0.001) reduced by pacing from 0.5 to 0 events per patient per year, with 21 patients experiencing no cardiac events during an average pacemaker follow-up of 49 months per patient. In 10 patients in whom the demand atrial pacing rate was faster than the intrinsic sinus rate, the average heart rate was increased 23 beats/min (from 58 to 81 beats/min) with pacing with reduction in the QT interval from 0.59 seconds to 0.46 seconds. CONCLUSIONS: The beneficial effects of pacing in high-risk LQTS patients probably relate to the prevention of bradycardia, pauses, and the shortening of long QT intervals--factors that are known to be arrhythmogenic in this syndrome. Permanent cardiac pacing reduces the rate of recurrent syncopal events in high risk LQTS patients, but it does not provide complete protection. PMID- 1914095 TI - Unsuspected echocardiographic abnormality in the long QT syndrome. Diagnostic, prognostic, and pathogenetic implications. AB - BACKGROUND: The idiopathic long QT syndrome (LQTS) is characterized by electrocardiographic abnormalities and by a high incidence of lethal arrhythmias. The present case/control study demonstrates the frequent occurrence of unusual and specific ventricular wall motion abnormalities in LQTS and their association with history of syncope or cardiac arrest. These anomalies were present in 23 of 42 LQTS patients (55%) and in two of 42 healthy controls (5%, p less than 0.0001) matched for age, sex, height, and weight. METHODS AND RESULTS: Two new measurements were developed to assess quantitatively the abnormalities observed. The first, Th1/2, is an index of the rapidity of the early contraction phase; the second, TSTh, is an index of the presence of a slow movement in the late thickening phase. Th1/2 was smaller in LQTS patients (15.0 +/- 4.1 versus 19.9 +/ 3.9% of the cardiac cycle, p less than 0.001), indicating that they reach half maximal systolic contraction more rapidly than controls. TSTh was greater in LQTS patients (9.37 +/- 6.82 versus 2.88 +/- 4.46%, p less than 0.001), indicating that they spend more time at a very low thickening rate. A peculiar double peak pattern of late thickening was present in 11 patients and in no controls. These abnormalities were more frequent in symptomatic than in asymptomatic patients (20 of 26, 77%, versus three of 16, 19%, p less than 0.005; relative risk, 2.75). They were not affected by beta-blockade or by left cardiac sympathetic denervation. The same echocardiographic abnormalities were produced by right stellectomy in nine of nine anesthetized dogs, were not dependent on cycle length, and were not modified by subsequent left stellectomy. CONCLUSIONS: This study demonstrates a previously unsuspected abnormality in the ventricular contraction pattern of LQTS patients and, for the first time, provides evidence that a noninvasively detected cardiac abnormality is associated with a higher risk for syncope/cardiac arrest. The experimental reproduction of this echocardiographic abnormality by right stellectomy indicates that this newly found clinical characteristic of LQTS does not contradict the "sympathetic imbalance" hypothesis. PMID- 1914096 TI - Polymorphous ventricular tachycardia associated with acute myocardial infarction. AB - BACKGROUND: During a 2.9-year period, 11 patients developed polymorphous ventricular tachycardia 1-13 days after acute anterior (seven patients) or inferior (four patients) myocardial infarction. None of the 11 patients had sinus bradycardia (mean heart rate, 90 +/- 23 beats/min), but three had a sinus pause immediately before the onset of polymorphous ventricular tachycardia. In all 11 patients, the QT interval and corrected QT interval (QTc) were normal or minimally prolonged (QT, 385 +/- 34 msec; QTc, 442 +/- 40 msec). None had significant hypokalemia (mean serum potassium concentration, 4.3 +/- 0.5 meq/l) or a grossly abnormal serum magnesium or calcium concentration (2.1 +/- 0.4 and 8.9 +/- 0.7 mg/dl, respectively). METHODS AND RESULTS: Immediately before the onset of polymorphous ventricular tachycardia, symptoms and/or electrocardiographic changes consistent with recurrent myocardial ischemia occurred in nine of 11 patients. One patient died before drug therapy could be initiated. Lidocaine was used in 10 patients and proved to be effective in only one. Intravenous procainamide was used in six patients: one improved, and five had recurrence of polymorphous ventricular tachycardia. Bretylium was used in five patients and was ineffective in all cases. Overdrive pacing was used in four patients and failed to suppress recurrent arrhythmias in all cases. Four patients with persistent polymorphous ventricular tachycardia unresponsive to lidocaine, procainamide, or bretylium responded to intravenous amiodarone. One patient with polymorphous ventricular tachycardia that was consistently preceded by ST segment elevation responded to intravenous nitroglycerin. Two patients with persistent polymorphous ventricular tachycardia and obvious recurrent ischemia unresponsive to pharmacological intervention responded to emergency coronary revascularization. A third patient who experienced recurrent angina and polymorphous tachycardia was initially stabilized with pharmacological therapy but subsequently underwent elective revascularization and has remained stable without antiarrhythmic therapy. CONCLUSIONS: Post-myocardial infarction polymorphous ventricular tachycardia is not consistently related to an abnormally long QT interval, sinus bradycardia, preceding sinus pauses, or electrolyte abnormalities. This arrhythmia has a variable response to class I antiarrhythmics but may be suppressed by intravenous amiodarone therapy. It is often associated with signs or symptoms of recurrent myocardial ischemia. Furthermore, coronary revascularization appears to be effective in preventing the recurrence of polymorphous ventricular tachycardia when associated with recurrent postinfarction angina. PMID- 1914097 TI - Randomized 4-week exercise program in patients with impaired left ventricular function. AB - BACKGROUND: This study was designed to determine the controlled effects of a short-term exercise rehabilitation program on patients with moderate-to-severe left ventricular dysfunction after a recent myocardial infarction. METHODS AND RESULTS: Thirty-nine male patients 51 +/- 8 years old with a large anterior myocardial infarction less than 10 weeks old were recruited for the study. The patients were randomly assigned to either one of two training or control groups on the basis of their resting ejection fraction: training, less than 30%; control, less than 30%; training, 31-50%; or control, 31-50%. Patients were evaluated for filling pressures, radionuclide ventriculography, heart volume, echocardiography, and work capacity. Patients who underwent training participated in an intensive 4-week in-hospital exercise program, whereas the control patients were restricted to a minimal activity program. Results indicated that there were no significant improvements in resting, submaximal, and maximal hemodynamic measurements as a result of the program. Mean work capacity and peak oxygen consumption improved significantly in the less-than-30% training group but was accompanied by a significant increase in mean pulmonary wedge pressure. Resting ejection fraction improved markedly in both less-than-30% training and control patients, but ejection fraction measures were not associated with work capacity. Training did not cause further deterioration in ventricular function. CONCLUSIONS: It was concluded that in the present study, exercise training had little or no effect on hemodynamic measurements and that the training effects achieved in patients with left ventricular dysfunction are most likely due to corrected impaired vasodilation, not necessarily to cardiac function. The importance of using a control group in this type of study and the wide interindividual variations in training responses are emphasized. PMID- 1914098 TI - Hemodynamic, renal, and hormonal responses to brain natriuretic peptide infusion in patients with congestive heart failure. AB - BACKGROUND: This study was designed to examine the hemodynamic, renal, and hormonal effects of brain natriuretic peptide (BNP) infusion in patients with congestive heart failure (CHF) and in control subjects. METHODS AND RESULTS: We infused synthetic human BNP at a rate of 0.1 micrograms/kg/min. BNP infusion decreased pulmonary capillary wedge pressure (control, from 5 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01; CHF, from 21 +/- 3 to 14 +/- 4 mm Hg, p less than 0.05) and systemic vascular resistance (control, from 1,264 +/- 75 to 934 +/- 52 dyne.sec.cm-5; CHF, from 2,485 +/- 379 to 1,771 +/- 195 dyne.sec.cm-5; p less than 0.01, respectively) and increased stroke volume index (control, from 49.9 +/ 2.7 to 51.5 +/- 2.3 ml/m2, p = NS; CHF, from 25.6 +/- 3.8 to 32.0 +/- 3.9 ml/m2, p less than 0.01). BNP infusion significantly increased urine volume (control, from 2.3 +/- 0.7 to 7.5 +/- 1.9 ml/min; CHF, from 0.8 +/- 0.2 to 5.3 +/- 1.0 ml/min; p less than 0.01, respectively), excretion of sodium (control, from 79.2 +/- 21.6 to 332.8 +/- 70.9 microEq/min; CHF, from 77.4 +/- 20.8 to 753.5 +/- 108.0 microEq/min; p less than 0.01, respectively), and excretion of chloride (control, from 72.5 +/- 18.4 to 256.0 +/- 43.3 microEq/min; CHF, from 74.0 +/- 19.6 to 708.8 +/- 103.3 microEq/min; p less than 0.01, respectively). Urinary excretion of sodium and of chloride in response to BNP infusion was higher in patients with CHF than in control subjects (p less than 0.01, respectively). BNP infusion increased the levels of plasma atrial natriuretic peptide (control, from 65 +/- 11 to 84 +/- 14 pg/ml; CHF, from 262 +/- 65 to 301 +/- 62 pg/ml; p less than 0.05, respectively) and decreased plasma aldosterone concentrations in both groups (control, from 43.3 +/- 12.1 to 27.3 +/- 7.1 pg/ml; CHF, from 91.1 +/- 34.3 to 66.3 +/- 27.2 pg/ml; p less than 0.05, respectively). CONCLUSIONS: We conclude that BNP infusion improves left ventricular function in patients with CHF by vasodilation and prominent natriuretic action. PMID- 1914099 TI - Endothelium-dependent vasodilation is attenuated in patients with heart failure. AB - BACKGROUND: Endothelial cells produce a number of substances, collectively termed endothelium-derived relaxing factor (EDRF), that promote local relaxation of vascular smooth muscle. Although studies have demonstrated defects in endothelium dependent vasodilation in animal models of hypertension, atherosclerosis, and heart failure, there are only limited data from human subjects because of the difficulty in obtaining fresh vascular segments. METHODS AND RESULTS: To address the hypothesis that endothelium-dependent vasodilation is attenuated in patients with heart failure, we measured forearm blood flow responses to the intra arterial administration of methacholine, a known stimulus of EDRF release through muscarinic receptors. In 14 normal subjects, a dosage range of methacholine increased forearm blood flow by 5.26 +/- 0.63, 10.50 +/- 0.63, and 13.22 +/- 0.86 ml/min/100 ml forearm volume (FAV); these responses were 1.98 +/- 0.46, 5.48 +/- 0.79, and 8.50 +/- 1.53 ml/min/100 ml FAV in 14 patients with heart failure. When pooled over all doses, the responses were strikingly less in the patients with heart failure (5.32 +/- 0.31 versus 9.52 +/- 0.60 ml/min/100 ml FAV; p = 0.0003). In a second study, the average difference in forearm blood flow responses between patients with heart failure and normal subjects with methacholine was significantly greater than the average difference between the groups with nitroprusside (4.04 +/- 1.10 versus 2.20 +/- 0.71 ml/min/100 ml FAV; p = 0.04). The decreased methacholine responses in the patients with heart failure were not related to age (r = 0.39; p = NS) or etiology because there was no difference in the responses between patients with ischemic heart disease and those with idiopathic cardiomyopathy. CONCLUSIONS: These data suggest that endothelium dependent vasodilation is attenuated in patients with heart failure. Although the mechanisms of the decreased endothelium-dependent responses in heart failure are not known, this impaired local vasodilation may contribute to abnormalities in vasoconstriction that are characteristic of heart failure. PMID- 1914100 TI - Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity. AB - BACKGROUND: Exertional fatigue, which frequently limits exercise in patients with chronic heart failure, is associated with early anaerobic metabolism in skeletal muscle. The present study was designed to examine the skeletal muscle metabolic response to exercise in this disorder and determine the relation of reduced muscle blood flow and skeletal muscle biochemistry and histology to the early onset of anaerobic metabolism in patients. METHODS AND RESULTS: We evaluated leg blood flow, blood lactate, and skeletal muscle metabolic responses (by vastus lateralis biopsies) during upright bicycle exercise in 11 patients with chronic heart failure (ejection fraction 21 +/- 8%) and nine normal subjects. In patients compared to normal subjects, peak exercise oxygen consumption was decreased (13.0 +/- 3.3 ml/kg/min versus 30.2 +/- 8.6 ml/kg/min, p less than 0.01), whereas peak respiratory exchange ratio and femoral venous oxygen content were not different (both p greater than 0.25), indicating comparable exercise end points. At rest in patients versus normals, there was a reduction in the activity of hexokinase (p = 0.08), citrate synthetase (p less than 0.02), succinate dehydrogenase (p = 0.0007), and 3-hydroxyacyl CoA dehydrogenase (p = 0.04). In patients, leg blood flow was decreased at rest, submaximal, and maximal exercise when compared to normal subjects (all p less than 0.05), and blood lactate accumulation was accelerated. In patients, during submaximal exercise blood lactate levels were not closely related to leg blood flow but were inversely related to rest citrate synthetase activity in skeletal muscle (r = -0.74, p less than 0.05). At peak exercise there were no intergroup differences in skeletal muscle glycolytic intermediates, adenosine nucleotides, or glycogen, whereas in patients compared to normal subjects less lactate accumulation and phosphocreatine depletion were noted (both p less than 0.05), suggesting that factors other than the magnitude of phosphocreatine depletion or lactate accumulation may influence skeletal muscle fatigue in this disorder. CONCLUSIONS: The results of the present study suggest that in patients with chronic heart failure reduced aerobic activity in skeletal muscle plays an important role in mediating the early onset of anaerobic metabolism during exercise. Our findings are consistent with the concept that reduced aerobic enzyme activity in skeletal muscle is, in part, responsible for determining exercise tolerance and possibly the response to chronic intervention in patients with chronic heart failure. PMID- 1914101 TI - Importance of two-dimensional echocardiographic assessment of left ventricular systolic function in patients presenting to the emergency room with cardiac related symptoms. AB - BACKGROUND: This prospective study was designed to test the hypothesis that the assessment of left ventricular systolic function at the time of emergency room (ER) presentation provides valuable diagnostic and prognostic information in patients with cardiac-related symptoms. METHODS AND RESULTS: The study is based on a 2-year follow-up of 171 consecutive patients evaluated in the ER for such symptoms. In the course of follow-up, one third of the patients (55 of 171) suffered a major cardiac event. For those with left ventricular systolic dysfunction (LVSD), the age-adjusted rate of early events (occurring within 48 hours of presentation) was more than eight times higher than for those without LVSD (26.9% versus 3.3%, p less than 0.01). For events occurring after 48 hours of ER presentation, LVSD was associated with a nearly fourfold excess of cardiac events (23.9% versus 6.4%, p less than 0.01). Other than advanced age, the most important confounder for early events included an abnormal electrocardiogram diagnostic for acute myocardial infarction. Confounders for late events included advanced age and a history of hypertension. LVSD on two-dimensional echocardiography (2DE) was the only finding associated with early and late events after controlling for other risk factors. In addition, the prediction of these events derived from the combination of historical, clinical, electrocardiographic, and 2DE findings was significantly improved when accounting for the presence or absence of LVSD (p less than 0.01). CONCLUSIONS: We conclude that the 2DE assessment of left ventricular systolic function provides valuable diagnostic and prognostic information in subjects presenting to the ER with cardiac-related symptoms. PMID- 1914102 TI - Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function. AB - BACKGROUND: Many asymptomatic patients with aorta regurgitation and normal left ventricular systolic function remain clinically stable for many years, but others ultimately develop symptoms or left ventricular dysfunction and require operation. To identify indexes of left ventricular function predictive of symptomatic and functional deterioration during the long-term course of asymptomatic patients, we studied 104 asymptomatic patients with chronic severe aortic regurgitation and normal left ventricular ejection fraction at rest. METHODS AND RESULTS: Serial echocardiographic (average, 7.8 per patient) and radionuclide angiographic (average, 5.0 per patient) studies were obtained over a mean follow-up period of 8 years (range, 2-16 years). By Kaplan-Meier life table analysis, 58 +/- 9% of patients remained asymptomatic with normal ejection fraction at 11 years, an average attrition rate of less than 5% per year; two patients died suddenly, four developed asymptomatic left ventricular dysfunction, and 19 underwent operation because symptoms developed. By univariate Cox regression analysis, many variables on initial study were associated with death, ventricular dysfunction, or symptoms, including age, left ventricular end systolic dimension and end-diastolic dimension, fractional shortening, and both rest and exercise ejection fraction (all p less than 0.001). The average rates of change of rest ejection fraction, fractional shortening, and end-systolic dimension were also associated with death or symptoms by univariate Cox analysis (all p less than 0.01). However, when all variables were included in a multivariate Cox analysis, only age (p less than 0.05), initial end-systolic dimension (p less than 0.001), and rate of change in end-systolic dimension and rest ejection fraction during serial studies (both p less than 0.05) predicted outcome. CONCLUSIONS: Thus, in addition to indexes of left ventricular function determined on initial evaluation, serial long-term changes in systolic function identify patients likely to develop symptoms and require operation. Patients have a higher risk of symptomatic deterioration if there is progressive change in end systolic dimension or resting ejection fraction during the course of serial studies. PMID- 1914103 TI - Relative risk analysis of angiographic predictors of restenosis within the coronary Wallstent. AB - BACKGROUND: Late angiographic narrowing has been observed following coronary implantation of the Wallstent. To identify the angiographic variables that predict restenosis within the stented segment, a retrospective study of data from the European Wallstent core laboratory was performed. METHODS AND RESULTS: Follow up angiograms (excluding patients with in-hospital occlusions) were analyzed for 214 lesions in 176 patients (78% restudy rate). The incidence of restenosis within the stented segment was 35% by lesion and 35% by patient for criterion 1 (greater than or equal to 0.72 mm loss in minimal luminal diameter) and 24% by lesion and 24% by patient for criterion 2 (diameter stenosis greater than or equal to 50% at follow-up). The association between 16 variables and restenosis was determined by a relative risk ratio assessment. Variables with significant risk ratios for restenosis with criterion 1 were use of multiple stents/lesion (relative risk, 1.56; 95% confidence interval [CI], 1.08-2.25) and oversized (unconstrained stent diameter exceeding reference diameter greater than 0.7 mm) stents (relative risk, 1.64; 95% CI, 1.10-2.45), and for criterion 2, oversizing by more than 0.70 mm (relative risk, 1.93; 95% CI, 1.13-3.31), bypass grafts (relative risk, 1.62; 95% CI, 0.98-2.66), use of multiple stents/lesion (relative risk, 1.61; 95% CI, 0.97-2.67) and residual diameter stenosis more than 20% post stenting (relative risk, 1.51; 95% CI, 0.91-2.50). CONCLUSIONS: It is concluded that several angiographic variables are significantly associated with late angiographic narrowing after stenting in the coronary arteries. We suggest that stent operators avoid excessive oversizing in the selection of stent diameter and the use of multiple stents per lesion to lessen the risk of late restenosis. PMID- 1914104 TI - Catheter ablation using radiofrequency current to cure symptomatic patients with tachyarrhythmias related to an accessory atrioventricular pathway. AB - BACKGROUND: Recent investigations have shown that cure of patients with symptomatic tachyarrhythmias related to an accessory atrioventricular pathway may be achieved by closed-chest electrode catheter ablation of the accessory connection. Direct current shocks have primarily been used for this purpose, but its applicability is limited because of the lack of controlled titration of electrical energy, the infliction of barotrauma, and the need for general anesthesia. Radiofrequency current has been proposed as an alternate energy source. METHODS AND RESULTS: Seventy-three symptomatic patients with Wolff Parkinson-White syndrome and 19 patients with only retrogradely conducting (concealed) pathways underwent ablative therapy with radiofrequency current. There were 71 accessory pathways located on the left side of the heart (57 free wall and 14 posteroseptal pathways) and 25 on the right side (11 free-wall, seven posteroseptal, and seven midseptal or anteroseptal pathways). In patients with right-sided pathways, ablation was attempted via a catheter positioned at the atrial aspect of the tricuspid annulus. In patients with a left-sided free-wall accessory pathway, a novel approach was used in which the ablation catheter was positioned in the left ventricle directly below the mitral annulus. Accessory pathway conduction was permanently abolished in 79 patients (86%). Growing experience and improved catheter technology resulted in a 100% success rate after the 52nd consecutive patient. Failures were mainly the result of inadequate catheters used initially or an unfavorable approach to left posteroseptal pathways. CONCLUSIONS: Catheter ablation of accessory atrioventricular pathways by the use of radiofrequency current is an effective and safe therapeutic modality for patients with symptomatic tachyarrhythmias mediated by these pathways. PMID- 1914105 TI - Electrophysiological properties in chronic lone atrial fibrillation. AB - BACKGROUND: Although the electrophysiological mechanisms underlying self sustaining atrial fibrillation (AF) are unclear, recent studies suggest that one requirement for reentry, slow conduction, is frequently present in patients with AF. However, these observations limited to paroxysmal AF may not necessarily apply to chronic AF. Therefore, electrophysiological properties of the atrium and sinus nodal function in chronic lone AF were evaluated. METHODS AND RESULTS: Electrophysiological studies were performed after electrocardioversion in 12 patients with chronic lone AF. Atrial enlargement was absent in the patients with AF. Twelve patients without atrial arrhythmias served as the control group. The patients with AF had a higher incidence of sinus nodal dysfunction, a shorter atrial effective refractory period (215 +/- 19 msec versus 238 +/- 23 msec, p less than 0.02), and a longer P wave duration than control patients (115 +/- 16 msec versus 86 +/- 16 msec, p less than 0.01). The conduction delay zone was significantly greater in patients with AF (60 +/- 12 msec) than that in the control patients (8 +/- 13 msec, p less than 0.01), and the maximal conduction delay was also greater in the study patients than those in the control group, both to the His bundle region (31 +/- 12 msec versus 10 +/- 15 msec, p less than 0.01) and to the coronary sinus (41 +/- 15 msec versus 15 +/- 11 msec, p less than 0.01). The fragmented atrial activity zone was wider in the study group (23 +/- 25 msec) than in control subjects (1.7 +/- 4 msec, p less than 0.02). Repetitive atrial firing was observed in four patients with AF but it was not seen in the control group. CONCLUSIONS: These electrophysiological features, which are manifestations of the abnormal atrial electrophysiology, would favor production of atrial reentry in chronic lone AF. PMID- 1914106 TI - Mitral regurgitation following mitral balloon valvotomy. Differing mechanisms for severe versus mild-to-moderate lesions. AB - BACKGROUND: This study was designed to evaluate the incidence and mechanisms of mitral regurgitation following mitral balloon valvotomy (MBV) in 40 consecutive patients with symptomatic tight pliable mitral stenosis. METHODS AND RESULTS: Transthoracic echocardiography with color flow mapping was performed before and 24 hours after the procedure. Patients who developed significant mitral regurgitation following MBV also underwent transesophageal echocardiography. The relation between increased mitral regurgitation and both valvular morphology and procedure-related factors was examined. Gorlin mitral valve area increased from 0.81 +/- 0.3 to 1.95 +/- 0.7 cm2 (p less than 0.001). No patient had more than 2+ mitral regurgitation by angiography and color Doppler prior to MBV. There was a moderate correlation between Doppler and angiographic increase in mitral regurgitation (r = 0.73, p less than 0.0001). By Doppler criteria 33 patients had no (n = 6) or mild (n = 27) increase in mitral regurgitation (group 1), and seven developed significant new mitral regurgitation (group 2). Baseline clinical, echocardiographic, and procedure-related data for the two groups were similar. Multiple regression analysis did not select any individual valve characteristic (valvular thickening, mobility, calcification, and subvalvular disease), total echocardiographic score, balloon diameter, or ratio of balloon to mitral annular diameter as disruption with a torn anterior or posterior mitral leaflet in six and a ruptured papillary muscle in one. Two of these patients have required mitral valve replacement (6 and 9 months following the procedure), whereas the remainder are significantly symptomatic. By contrast, mitral regurgitation in group 1 either occurred at the site of commissural split (n = 20) or was associated with prolapse of the anterior mitral leaflet (n = 6). CONCLUSIONS: Thus, severe new mitral regurgitation following MBV is due to noncommissural tearing of the mitral leaflet and confers an adverse long-term prognosis. A mild increase in mitral regurgitation following MBV is frequent and occurs at the site of commissural split or is associated with prolapse of the anterior leaflet. Furthermore, in this study, an increase in mitral regurgitation could not be predicted from any valvular or procedure-related factor. PMID- 1914107 TI - Dissolution of peripheral arterial thrombi by ultrasound. AB - BACKGROUND: We have previously shown that continuous-wave ultrasound can rapidly dissolve human thrombi in vitro, with 99% of all residual particles measuring less than 10 microns in diameter. To assess the effects of pulsed-wave ultrasound energy on whole blood clots, 1) in vitro studies were preformed to assess precisely the rates of clot disruption and to quantify particulate size, and 2) in vivo studies were performed to assess the efficacy and safety of catheter delivered ultrasound for intra-arterial thrombus dissolution. METHODS AND RESULTS: In vitro, we studied 50 samples of human whole blood clots and using an 89-cm-long wire probe, applied pulse-wave energies from 8 to 23 W. The corresponding peak-to-peak tip displacement range was 63.5 - 102 microns. We studied arterial thrombosis in vivo in 21 canine superficial femoral arteries. To produce an acute thrombosis, 200 units of thrombin followed by 2 ml of 72-hour old autologous clot were injected into a 5-7-cm segment of femoral artery and left to coagulate for 2 hours. Ultrasound energy was intermittently applied at a frequency of 20 kHz with a prototype ultrasound wire ensheathed in a catheter and directed to clots by fluoroscopy. In nine cases, angioscopic guidance was used to put the probe into direct contact with the intra-arterial thromboses. In vitro clot dissolution times were inversely related to the ultrasound power output (r = 0.95). All in vivo canine thromboses were disrupted in 4 minutes or less. All successful recanalizations were confirmed by angiography and in nine cases by angioscopy as well. Angioscopy demonstrated that probe activation caused rapid clot disruption. Histological studies of the vessels showed no evidence of thermal or cavitation injury, occlusive distal embolization, or perforation. CONCLUSIONS: Our findings in this experimental canine model suggest that ultrasound clot dissolution has the potential to be an effective and safe alternative to current treatment modalities for peripheral arterial thrombosis. PMID- 1914108 TI - Regional control of atrial fibrillation by rapid pacing in conscious dogs. AB - BACKGROUND: In five chronically instrumented conscious dogs, we studied the effects of rapid pacing on sustained electrically induced atrial fibrillation. METHODS AND RESULTS: Twenty-three unipolar atrial electrograms were recorded simultaneously from the bundle of Bachmann and the lateral wall of the right and left atria. During sustained atrial fibrillation, the surface electrocardiogram showed continuous irregularities of the baseline without P or F waves as well as an irregular ventricular rhythm with narrow QRS complexes. The atrial electrograms showed rapid irregular activity with a median cycle length of 85 +/- 8 msec and a range (P5-95) of 33 +/- 18 msec. Overdrive pacing of atrial fibrillation was performed using symmetric biphasic rectangular stimuli (2-msec duration, sixfold that of threshold) applied to a pair of stimulating electrodes at the left atrial appendage. Stimulation was started at pacing intervals of about 10 msec longer than the local median fibrillation interval and subsequently shortened in steps of 1 msec. At a critical pacing interval slightly shorter than the median fibrillation interval, the atrium around the pacing site was suddenly captured by the electrical stimuli. The area of local capture had a diameter of 6.1 +/- 1.6 cm. The time window of capture was 12 +/- 4 msec. CONCLUSIONS: These observations show that during electrically induced atrial fibrillation in chronically instrumented conscious dogs, a short excitable gap is present, permitting regional control of the fibrillatory process by rapid pacing. PMID- 1914109 TI - Evaluation of contractile state by maximal ventricular power divided by the square of end-diastolic volume. AB - BACKGROUND: Maximal ventricular power (PWRmax) reflects contractile state and has the potential to be noninvasively determined. However, its sensitivities to preload, afterload resistance, and inotropic state are incompletely defined. The present study determines these dependencies and proposes a novel power-based contractile index that is little altered by load. METHODS AND RESULTS: Seven open chest, autonomically blocked dogs were instrumented with a proximal aortic flow probe, central aortic and ventricular micromanometers, and a conductance catheter for ventricular chamber volume. Preload was transiently reduced by left atrial hemorrhage, and afterload was increased by intra-aortic balloon inflation. Inotropic state was pharmacologically altered by lidocaine, dobutamine, propranolol, or verapamil. PWRmax was highly preload sensitive, altering 1.7 +/- 0.1-fold a given percent change in end-diastolic volume (EDV). This preload dependence was reduced by dividing PWRmax by EDV but was virtually eliminated when PWRmax was divided by EDV2. This latter index also displayed little change in response to as much as 60% increases in afterload resistance. PWRmax/EDV2 varied directly with inotropic state, correlating to both the slope (Ees) of the end-systolic pressure-volume relation (PWRmax x 1,000/EDV2 = 0.31 x Ees - 0.04, r = 0.82, p less than 0.001) and the slope (A) of the dP/dtmax-EDV relation (PWRmax x 1,000/EDV2 = 0.025 x A + 0.02, r = 0.86, p less than 0.001). PWRmax values determined from the product of ventricular pressure and flow versus central aortic pressure and flow were nearly identical over a broad loading range, indicating that PWRmax may be noninvasively assessed (i.e., without requiring left ventricular chamber pressure). CONCLUSIONS: PWRmax divided by EDV2 provides a measure of contractile function that is little influenced by loading conditions and has potential for noninvasive clinical use. PMID- 1914110 TI - Modulation of drug effects by regional sympathetic denervation and supersensitivity. AB - BACKGROUND: Regional sympathetic denervation, such as that produced by a myocardial infarction, causes electrophysiological heterogeneity in the ventricles. The purpose of this study was to test the hypothesis that such denervation could cause drugs to exert heterogeneous myocardial effects. METHODS AND RESULTS: Sympathetic stimulation increases the amplitude of cesium chloride induced early afterdepolarizations (EADs). The amplitude of these induced EADs was used to determine whether drug responses were different in innervated versus denervated areas of the heart. A canine model of sympathetic denervation was created at the cardiac apex by either transmural myocardial infarction (n = 19) or phenol application (n = 11). Cesium chloride (84 mg/kg) was infused while monophasic action potential recordings were simultaneously obtained from the base and apex of the left ventricle using an epicardial contact electrode. We found that control (innervated) dogs (n = 17) showed no difference in the EAD amplitude recorded from the apex compared with the base. In dogs with apical sympathetic denervation, the EAD amplitude was greater at the innervated base during ansae subclaviae stimulation than at the denervated apex (25.8 +/- 6.6% at base versus 18.8 +/- 6.7% at apex, p less than 0.001). However, during norepinephrine infusion, the EADs recorded from the denervated apex were greater than those recorded from the innervated base (23.3 +/- 7.6% at apex versus 20.6 +/- 6.0% at base, p less than 0.02) due to denervation supersensitivity. CONCLUSIONS: These data show that regional myocardial denervation creates autonomic and electrophysiological heterogeneity and the substrate for heterogeneous drug actions. This drug-induced electrophysiological heterogeneity may be another mechanism for proarrhythmia. PMID- 1914111 TI - Dietary fish oil reduces leukocyte/endothelium interaction following systemic administration of oxidatively modified low density lipoprotein. AB - BACKGROUND: In vitro and in vivo experiments have demonstrated the role of oxidatively modified low density lipoprotein (oxLDL) in eliciting leukocyte/endothelium interaction during early atherogenesis. METHODS AND RESULTS: In the present study we investigated the effect of dietary fish oil on oxLDL-induced leukocyte/endothelium interaction using intravital fluorescence microscopy in the dorsal skinfold chamber model in awake Syrian golden hamsters. Hamsters were fed for 4 weeks prior to the experiments with either standard laboratory chow or a diet supplemented with 5% of a fish oil concentrate (18% eicosapentaenoate, 12% docosahexaenoate). The efficacy of the fish oil diet was demonstrated by the incorporation of fish oil-derived omega-3 fatty acids into plasma, leukocyte, and erythrocyte lipids. In control hamsters (n = 7) and fish oil-fed hamsters (n = 7), leukocyte/endothelium interaction was assessed in the time course after intravenous injection of human LDL (4 mg/kg), oxidized by 7.5 microM Cu2+ (6 hours, 37 degrees C). In control hamsters, injection of oxLDL elicited the rolling and sticking of leukocytes to the endothelium of arterioles and postcapillary venules with a maximum 15 minutes after injection (arterioles: from 3 +/- 1 to 91 +/- 25 cells/mm2 at 15 minutes; venules: from 13 +/- 6 to 150 +/- 46 cells/mm2 at 15 minutes; mean +/- SD). This phenomenon was significantly reduced in fish oil-fed hamsters, where 15 minutes after injection of oxLDL leukocyte sticking reached a maximum of only 15 +/- 7 and 20 +/- 5 cells/mm2 in arterioles and postcapillary venules, respectively (p less than 0.01 versus control animals). CONCLUSIONS: The results of the present study suggest that inhibition of leukocyte/endothelium interaction may be one of the mechanisms by which dietary fish oil exerts its protective effects on experimental and clinical atherogenesis. PMID- 1914112 TI - Reduction in thrombus formation by placement of endovascular stents at endarterectomy sites in baboon carotid arteries. AB - BACKGROUND: Although antithrombotic therapies with aspirin, dipyridamole, and heparin have decreased thrombo-occlusive events, they have not abolished these complications. Endovascular mechanical support, first reported by Dotter in 1969, has been proposed as a means to reduce both acute and chronic vessel closure by providing a supporting framework for the disrupted and sometimes dissected arterial wall. METHODS AND RESULTS: To determine the effects of placing self expanding stainless steel wire endoprostheses on the accumulation of thrombus at sites of carotid artery endarterectomy we measured platelet deposition continuously for 90 minutes and at 24 and 48 hours by gamma camera imaging of autologous 111In-labeled platelets in six stented and nonstented endarterectomized baboons that received heparin but no antiplatelet agents. At nonstented endarterectomy sites 5.36 +/- 1.25 x 10(8), 4.78 +/- 0.98 x 10(8), and 4.55 +/- 0.81 x 10(8) platelets per cm were deposited at 30, 60, and 90 minutes, respectively. In contrast, stented endarterectomy sites accumulated 0.99 +/- 0.31 x 10(8), 0.66 +/- 0.33 x 10(8), and 0.80 +/- 0.36 x 10(8) platelets per cm at 30 minutes (p = 0.02), 60 minutes (p = 0.004), and 90 minutes (p = 0.002), respectively. Platelet deposition remained reduced at 24 and 48 hours in stented endarterectomized carotid arteries (ECAs) when assessed as a ratio between net radioactivity in the endarterectomized region versus whole blood radioactivity (p = 0.006 and p = 0.009, respectively). Both stented and nonstented ECAs remained patent acutely, although two of six nonstented ECAs occluded by 30 days. By comparison 11 of 14 nonstented ECAs remained patent in another group of control animals. Scanning electron microscopy of control and stented arteries at 30 days demonstrated equivalently confluent endothelium. CONCLUSIONS: We postulate that endovascular stents reduce the thrombogenic effects of flap formation, tearing, dissection, and vasospasm in ECAs. PMID- 1914113 TI - Influx of neutrophils into the walls of large epicardial coronary arteries in response to ischemia/reperfusion. AB - BACKGROUND: There are several clinical situations in which large epicardial coronary arteries are deprived of blood flow, such as occurs when an obstructing thrombus or embolus lodges within a vessel or during coronary dissection. There is little information concerning the effect of flow deprivation on large epicardial coronary arteries. METHODS AND RESULTS: We studied a model in which a segment of a large epicardial coronary artery was deprived of blood flow using both proximal and distal clamps for 3 hours followed by reperfusion. On examination by light microscopy of cross sections of the arteries, 19 +/- 6 neutrophils were present in the intima of ischemic/reperfused vessels, whereas only a mean of 4 +/- 3 (SEM) were present in the intima of nonischemic vessels (p less than 0.02). On average, there were 17 +/- 9 neutrophils just under the elastic lamina in ischemic/reperfused vessels versus none in the nonischemic vessels (p less than 0.05); there were 16 +/- 10 neutrophils present within the media of ischemic/reperfused vessels, and none (p less than 0.05) in the nonischemic vessels. Electron microscopic analysis revealed that neutrophils in the ischemic/reperfused vessels were often "sandwiched" between the endothelial cells and the elastic lamina. Ultrastructural abnormalities within the myocardium also revealed damage to the microvasculature, including the presence of neutrophils within the vessels and erythrocyte stasis. To rule out the possibility that findings in the large epicardial arteries were due to toxic substances from static blood within the isolated arterial segment, a protocol was performed in which blood was removed from the isolated segment. Again, neutrophil infiltration into the vessel was observed. Resting mean epicardial coronary artery blood flow before coronary occlusion was 19 +/- 3 ml/min; mean coronary blood flow 2.5 hours after reperfusion was identical at 19 +/- 3 ml/min. Response to both endothelial-dependent vasodilation (acetylcholine) and endothelial independent vasodilation (nitroglycerin) challenges was normal early after reperfusion but was depressed late after reperfusion, suggesting progressive vascular dysfunction and hence a form of vascular reperfusion injury in this model. CONCLUSIONS: When large epicardial coronary arteries are deprived of blood flow, followed by reperfusion in this model, neutrophils migrate into the vessel wall as well as into the microvasculature. These abnormalities are associated with reduced endothelial-dependent and endothelial-independent coronary vasodilator reserve. PMID- 1914114 TI - Ultrasonic energy. Effects on vascular function and integrity. AB - BACKGROUND: Ultrasonic energy transmitted via flexible wire probes provides a new means of ablating atherosclerotic plaque. We studied the effects of ultrasonic energy (20 kHz) delivered via a ball-tipped wire probe on arterial vasomotor behavior in rabbit thoracic aortas in a perfused whole-vessel model. METHODS AND RESULTS: After precontraction with phenylephrine (10(-5) M) or KCl (60 mM), the effects of ultrasonic energy (0.7-5.5 W x 60 seconds, 42-330 J) on arterial vasomotor behavior were measured using long-axis ultrasonic vessel imaging of the proximal (ultrasonic probe-treated) and distal (untreated) control segments. The efficacy of plaque ablation at these same probe-tip power outputs was evaluated in atherosclerotic, human cadaver iliofemoral arteries. Ultrasonic energy caused dose (energy)-dependent relaxation in rabbit aortas after precontraction with phenylephrine in arteries with endothelium (n = 8) and without endothelium (n = 8) (p less than 0.001 versus ultrasound treated at power outputs of 2.9 and 5.5 W). There was no difference in the relaxation dose responses between endothelialized and endothelially denuded segments (p = NS). Ultrasonic energy also caused significant relaxation (67 +/- 8%) after voltage-dependent precontraction with 60 mM KCl. Temperature measurements revealed less than 1 degrees C warming of the vessel wall during as long as 2 minutes of treatment at a power output of 5.5 W. Pathological examination showed no smooth muscle injury at (moderate) power outputs that caused arterial relaxation. At probe-tip power outputs of 2.9-5.5 W, ultrasonic energy recanalized two of two totally occluded cadaveric iliofemoral vessel segments. The ultrasonic ablation catheter was also demonstrated to cause arterial relaxation in a recanalized canine femoral artery in vivo. CONCLUSIONS: Ultrasonic energy delivered via a flexible-wire probe produces dose-dependent, endothelium-independent smooth muscle relaxation capable of reversing both receptor-mediated and voltage-dependent vasoconstriction in vitro. At moderate power outputs, this relaxation response does not appear to be due to thermal effects or irreversible smooth muscle cell injury. This vasorelaxant effect of ultrasonic energy is also apparent in vivo, at doses that effectively ablate atherosclerotic plaque, and may improve the safety of arterial recanalization using ultrasonic energy. PMID- 1914115 TI - Comparison of 99mTc-teboroxime with thallium for myocardial imaging in the presence of a coronary artery stenosis. AB - BACKGROUND: This study tested the hypotheses in the setting of a coronary artery stenosis that 1) planar 99mTc-teboroxime myocardial scans are capable of providing a good estimate of relative coronary flow reserve, and 2) delayed washout of the tracer from the myocardium is a marker of reduced myocardial blood flow and, in certain cases, myocardial ischemia. METHODS AND RESULTS: Experiments were conducted in eight closed-chest domestic swine prepared with an artificial stenosis that reduced diameter of the left anterior descending coronary artery by 80%. Measurements of hemodynamics, regional myocardial blood flow, oxygen, and lactate metabolism were made 1) at baseline, 2) after 5 minutes of intravenous infusion of adenosine and neosynephrine ("stress"), and 3) at recovery 2 hours after discontinuing the adenosine/neosynephrine infusion. Simultaneous intravenous injection of teboroxime (approximately 9 mCi) and thallium (approximately 3.5 mCi) was made at peak stress, and serial planar teboroxime imaging began 1-2 minutes later. Scans were made in dynamic mode for 30 seconds each for 7 minutes after which a stress thallium scan (7 minutes acquisition) was obtained. A redistribution thallium scan was made 2 hours later after which a repeat teboroxime injection followed by serial imaging for 7 minutes was performed. The animal was then killed, and the heart removed for determination of microsphere activity. Under baseline conditions, transmural myocardial blood flow (ml/min/g) distal to the stenosis (1.06 +/- 0.17) was reduced (p less than 0.01) compared with the normally perfused circumflex zone (1.50 +/- 0.31). In response to intravenous infusion of adenosine/neosynephrine, flow increased (p less than 0.01) compared with baseline in both distal (2.00 +/- 0.84) and circumflex (4.67 +/- 1.55) zones. However, the distal : circumflex flow declined (0.45 +/- 0.17) compared with baseline (0.73 +/- 0.17; p less than 0.01). Two hours later flow had returned to baseline levels in both zones, and lactate production during stress (-41.7 +/- 37.5 mumol/min/100 g) had reverted to consumption (13.6 +/- 7.7; p less than 0.05). Analysis of stress teboroxime scans demonstrated 1) an increase (p less than 0.01) in the ischemic : normal zone (IZ:NZ) count between 30-second (0.50 +/- 0.14) and 7-minute scans (0.61 +/- 0.11); 2) a good correlation between the 30-second scan IZ:NZ count and the stress distal : circumflex flow (0.45 +/- 0.17; r = 0.74; p less than 0.05; slope = 0.90; intercept = 0); and 3) a close correlation between the IZ:NZ count of the 7 minute scan (0.61 +/- 0.11) and the recovery distal : circumflex flow (0.69 +/- 0.21; r = 0.89; p less than 0.01). The IZ:NZ count also increased (p less than 0.01) between 30-second (0.65 +/- 0.15) and 7-minute (0.72 +/- 0.14) scans following rest injection of teboroxime. As anticipated, serial thallium scans demonstrated evidence of redistribution between stress (IZ:NZ count = 0.62 +/- 0.08) and recovery (IZ:NZ count = 0.75 +/- 0.06; p less than 0.01) time points. The stress thallium scan IZ:NZ, however, was greater than that of the 30-second teboroxime scan as well as that of the stress distal : circumflex flow. CONCLUSIONS: Accordingly, the data indicate that 1) myocardial imaging with 99mTc teboroxime is valuable in the noninvasive assessment of relative coronary flow reserve and that 2) delayed washout of the tracer from the myocardium reflects reduced myocardial blood flow and, under conditions comparable to those of the present study, may be a marker of myocardial ischemia. PMID- 1914116 TI - Proarrhythmic effects of flecainide. Experimental evidence for increased susceptibility to reentrant arrhythmias. AB - BACKGROUND: The goal of this study was to investigate the nature and electrophysiological mechanisms of the proarrhythmic effects of flecainide in Langendorff-perfused rabbit hearts. METHODS AND RESULTS: A thin layer of epicardium was obtained by an endocardial cryotechnique in 10 Langendorff perfused rabbit hearts. Six other hearts were kept intact. Programmed electrical stimulation using up to three closely coupled premature stimuli and burst pacing was used to test the inducibility of arrhythmias both during control and administration of 1 micrograms/ml flecainide. During control, in the thin layer of epicardium, application of one to three premature stimuli induced nonsustained ventricular tachycardia in out of 10 hearts, and burst pacing induced nonsustained ventricular tachycardia in four hearts and sustained ventricular tachycardia in two hearts. During administration of 1 microgram/ml flecainide, application of one to three premature stimuli induced sustained ventricular tachycardia in five hearts, and burst pacing induced sustained ventricular tachycardia in nine hearts. All tachycardias were based on circus movement of the impulse around arcs of functional block. During administration of flecainide, different locations of the arc of block could be found in the same heart, leading to different reentrant circuits with different cycle lengths. In the control group of six intact hearts, application of up to three closely coupled premature stimuli in all cases induced ventricular fibrillation both during control and administration of flecainide. CONCLUSIONS: Flecainide alters propagation of the impulse in thin surviving layers of myocardium in a manner that facilitates the induction of functionally determined reentry. PMID- 1914117 TI - National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry as a standard for comparison of new devices. When should we use it, and what should we compare? PMID- 1914118 TI - Experimental issues in assessment of G protein function in cardiac disease. PMID- 1914119 TI - Is QT interval prolongation a strong or weak predictor for cardiac death? PMID- 1914120 TI - Exercise in patients with impaired left ventricular function. PMID- 1914121 TI - Reduced aerobic enzyme activity in skeletal muscles of patients with heart failure. A primary defect or a result of limited cardiac output? PMID- 1914122 TI - Experimental models of reentry, antiarrhythmic, and proarrhythmic actions of drugs. Complexities galore! PMID- 1914123 TI - Fixed and floating references in wall motion analysis. PMID- 1914124 TI - Relation of depression and mortality after myocardial infarction in women. PMID- 1914125 TI - Passive smoking and heart disease. PMID- 1914126 TI - The dipyridamole-thallium test. PMID- 1914127 TI - Abstracts from the 64th scientific sessions, American Heart Association. Anaheim, California, November 11-14, 1991. PMID- 1914128 TI - [Effect of acupuncture analgesia on synapses of paraventricular nucleus observed with transmission electron microscope]. AB - In order to study the ultrastructural change of the paraventricular nucleus of hypothalamus during the electro-acupuncture, 13 healthy and adult rats were divided into control group and electro-acupuncture group. The results are as follows: 1. The synapses of the paraventricular nucleus mainly belong to the axodendricular asymmetrical synapses and contain a lot of round clear synaptic vesicles. 2. The round clear synaptic vesicles of the paraventricular nucleus in the electro-acupuncture group are much fewer than those in the control group. The difference is very significant (P less than 0.01). This suggests that the paraventricular nucleus is involved in the electroacupuncture analgesia. PMID- 1914129 TI - [Effect of electrical stimulation and lesion of N reticularis paragigantocellularis lateralis on acupuncture analgesia in rats]. AB - The present study was aimed to investigate the role of the reticularis paragigantocellularis lateralis (RPGL) in acupuncture analgesia. Tail-flick response to electrical stimulation of the tail skin was taken as index of pain response. The first part of the study consisted of four groups: (1) surgical control, (2) electro-acupuncture, (3) electrical stimulation of RPGL, and (4) stimulation of RPGL simultaneously with electro-acupuncture. The pain threshold in the first group was quite stable during the experiments, but increased significantly after electro-acupuncture and/or brain stimulation (n = 14, P less than 0.01; n = 8, P less than 0.001; n = 14, P less than 0.001). The pain threshold of the fourth group increased much more than the second and the third group (P less than 0.001, P less than 0.01). In the second part of the study, the effect of electro-acupuncture was reduced significantly after electrical lesion of the RPGL unilaterally (n = 12, P less than 0.01). The present work indicates that electrical stimulation of RPGL enhances electro-acupuncture analgesia, whereas the lesion of RPGL reduces it. It is suggested that RPGL plays a role in acupuncture analgesia. PMID- 1914130 TI - [Role of ventrolateral medullary area in the effect of electrical needling "Neiguan" point on improving acute myocardial ischemia in rabbits]. AB - 40 healthy rabbits were anesthetized with 20% urethane and divided into 4 groups in same number: 1) electroacupuncture group physiological saline was applied locally on the S area of the ventral surface of the medulla: 2) naloxone group, naloxone (5 mg/ml. PH 6.5-7) was applied on the S area: 3) propranolol group, propranolol (5 mg/ml. pH 7.0) was applied on the S area: 4) control group, physiological saline was applied on the S area. The state of regional myocardial ischemia of the rabbits was caused by ligating the LAD for 20 minutes. The changes of the blood pressure and the ST values of standard lead II of ECG were observed before ligating and, at 5', 10', 15', 20', 25', 30', 35', 40', 45', 50', 55' and 60' after loosening respectively. Electroacupuncture was applied on "Neiguan" points bilaterally at 10' after ligating for 60 minutes (intensity 6-8 volt, frequency 60/min). The average potential changes of the ST values of standard lead II of 5 times were used as the index to evaluate myocardial ischemia and its recovery course. The followings are the main results of our observation: There were no statistical difference, of blood pressure and the ST values between the four groups before ligation. At 10 minutes after ligation, the ST values were elevated markedly, but there were no statistical significances between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914131 TI - [Effect of acupuncture on neuronal loss induced by axotomy in the rat hypoglossal nuclei]. AB - It was reported previously that acupuncture promotes regeneration of rat's peripheral nerve. In order to study the effect of acupuncture on recovery of motoneuronal lesion and regeneration of central nervous system, we studied the effect of acupuncture on neuronal loss induced by axotomy in the rat hypoglossal nuclei. A total of 6 pairs of rats (acupunctured and controls in pairs) were used, (each pair of) the rats were paired of the same litter and sex. After the right hypoglossal nerves were severed, rats were reared for 14 days. In this period, we gave acupuncture therapy to the acupunctured rats but nothing to the controls. After perfusion, serial paraffin sections of brain stems of rats were cut and stained with cresyl violet. Serial sections per rat were used for counting the perikaryon of the hypoglossal nuclei. The reduced percentage of neuronal population followed axotomy was calculated. It was found that neuronal loss was less severe in acupunctured rats. Difference in the reduced percentage of neuronal population between acupunctured rats and controls was significant statistically. It was shown that acupuncture increased survival of lesioned neurons, and thus acupuncture may be helpful to the recovery of neuronal lesion. The detailed mechanism is going to be explored. PMID- 1914132 TI - [C fiber is not necessary in electroacupuncture analgesia, but necessary in diffuse noxious inhibitory controls (DNIC)]. AB - Experiments were carried on rats. We applied capsaicin topically on sciatic nerve and used the techniques of extracellular recording and nerve trunk recording, Our results showed that the size of C compound action potentials in nerve trunk and C fiber response of spinal cord WDR neurons were decreased by at least 70% (mean) after topical application of capsaicin (250 micrograms) on the nerve, but A compound action potentials and A fiber response did not change significantly. It indicated that capsaicin blocked C fiber conduction selectively. Electroacupuncture (EA: 100 Hz, 0.1 ms, 3V) applied on left Zusanli (S36) and Sanyinjiao (Sp6) points inhibited C fiber response of spinal WDR neurons in the right side. The effect was similar to animal behavior analgesia elicited by EA. After applying capsaicin (250 micrograms) topically on left sciatic nerve, the inhibitory effect of EA on WDR neurons remained essentially intact (from 61.3 +/- 12.0% to 59.0 +/- 11.6%, n = 6, P greater than 0.05). It indicated that C fiber was not important in EA analgesia. Noxious heat (NH) applied on left hind paw by immersing the hind paw into 52 degrees C water inhibited C fiber response of spinal WDR neurons in the right side. It was called diffuse noxious inhibitory controls (DNIC). After applying capsaicin (250 micrograms) topically on left sciatic nerve, the inhibitory effect of NH on WDR neurons was dramatically decreased (from 77.7 +/- 8.5% to 8.1 +/- 8.9%, n = 6, P less than 0.001). It indicated that C fiber was important in DNIC. Both inhibitory effects of NH and EA were not changed by vehicle treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914133 TI - [Research on the relationship between central acetylcholine and acupuncture analgesia]. AB - The article systematically reported our physiological and biochemical work on the relationship between central acetylcholine and acupuncture analgesia. The results indicate: 1. Acupuncture on acupoints could produce analgesia. 2. Ach contents in cerebrospinal fluids and brain increased under acupuncture analgesia. 3. AChE activities iu brain elevated under acupuncture analgesia. 4. ChE inhibitor reinforced the effects of acupuncture and inhibitor of ACh synthesis could inhibit the effects of acupuncture, which could be reversed by administration of ACh and chlorocholine. M-AChR antagonists could also inhibit the effects of acupuncture. 5. The turnover rate of ACh in diencephalon, caudate nucleus and spinal dorsal horn accelerated when acupuncture analgesia. The discussion was given on the variation of metabolic dynamics in combination with related literature. PMID- 1914135 TI - [Response properties of SI cortical neurons to electro-acupuncture and manual acupuncture in the rat]. AB - Single SI cortical neurons were recorded extracellularly with glass micropipettes, and their response properties to electro-acupuncture (EA) of contralateral Tsusanli (St. 36) and Fenglung (St. 40), or to manual acupuncture (MA) of Tsusanli were observed in unanesthetized and paralyzed rats. In 46 rats, a total of 474 neurons were isolated in the hindlimb representation area of SI cortex. Among these neurons, 228 responded to peripheral mechanical stimulation, and could be classified as cutaneous neurons, deep neurons and cutaneous-deep convergent neurons. Thirty five of them were identified as nociceptive neurons. Neurons of various sensory neurons and with receptive fields (RFs) located in the contralateral hindlimb responded to EA. Significant difference (P less than 0.01) existed between the stimulation thresholds of cutaneous neurons (2.39 +/- 0.27V) and those of deep neurons (4.12 +/- 0.48V). There was no significant difference between the thresholds of nociceptive and non-nociceptive neurons. The typical response of SI neurons to single EA stimulation consisted of early discharges with a latency of 11.57 +/- 0.39 msec and late train discharges with a latency of 54.79 +/- 4.07 msec. A period of inhibition frequently intervened between the two groups of discharges. In a small portion of neurons, only a period of inhibition was produced. The responsiveness of neurons decreased markedly when the frequency of repeated EA stimulation was increased from 1 Hz to 50 Hz. Neurons of various sensory modalities responded to MA as well. Judging by RF distribution of the responsive neurons, however, the extent of action of MA was smaller than that of EA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914134 TI - [Studies on the relationship between acupuncture analgesia and testosterone or dihydrotestosterone in blood plasma]. AB - 55 rats (Wistar, Male, 250-350 g) were divided into 4 groups: (1) BTA (bilateral testectomy + adrenalectomy) group, (2) BT (bilateral testectomy) group, (3) BA (bilateral adrenalectomy) group, (4) SO (sham operation) group. EA was applied to bilateral "Tsusanli" points of each animal at 72 h. after operation. The potassium iontophoretic colorimetry was used to determine the pain threshold of rats, radioimmunoassay was used to measure the contents of T and DHT in femoral vein blood. T, DHT and the pain threshold of each animal were measured before operation, at 72 h, after operation and after EA, but for the SO group the measurement was done once at 72 h. after im testosterone phenylacetate. RESULTS: The content of T in BTA and BT groups were decreased. significantly at 72 h. after operation, but the changes of the pain threshold were similar to BA and SO groups. After EA the content of T in BT and SO groups were raised significantly (P less than 0.01), but in BT group raised slightly (P greater than 0.05). It was found in all animals that the content of DHT and the pain threshold were significantly elevated at 45 min after EA. No effect upon the pain threshold and EA analgesia was observed in SO group after im testosterone phenylacetate. CONCLUSION: T (from testes and adrenal) and DHT rose markedly after EA. Increasing T and DHT or decreasing T in plasma had no effect upon the pain threshold and EA analgesia. It is suggested that T and DHT in plasma may not play a role in the EA analgesia, in the other hand, EA may be used for improving the hypogonadal condition. PMID- 1914136 TI - Effect of intraventricular injection of 5,6-DHT on activities of nucleus raphe magnus in rats. PMID- 1914137 TI - [Effects of morphine and electro-acupuncture on the time lock and not-time lock responses of cortical unit discharges evoked by nociceptive stimulation in cats]. AB - In order to study the effects of morphine and electro-acupuncture(EA) on non-time lock response (N-TLR) and time-lock respone (TLR) of nociceptive unit discharges. N-TLR was shown by interspike interval mean function (ISIMF) and TLR by normalized cross-covariance function (NCCVF) reflecting the relationship between stimulation and response. The results showed that the N-TLR elicited by the noxious stimulation appeared as a decrease of ISIMF. Which was depressed obviously by EA and morphine, but inhibitory effect of EA was more rapid than morphine, that both EA and morphine inhibited mainly the late peak of the NCCVF elicited by the noxious stimulation, but inhibitory effect of EA was more rapidly developing and more quickly recovering than that of morphine. The inhibitory effect of EA on the early peak was very little. From above results it was suggested that the P-ED elicited by the noxious stimulation could be inhibited by both EA and morphine, but the degree and the speed of inhibition were difference. PMID- 1914138 TI - Progestin receptor cells in mouse cerebral cortex during early postnatal development: a comparison with preoptic area and central hypothalamus using autoradiography with [125I]progestin. AB - The distribution of progestin target cells in the cerebral cortex and the effect of estrogen treatment was assessed during the critical period of brain development and compared with the preoptic/central hypothalamic regions. [125I]progestin was injected into 0, 2, 8, and 12 day postnatal mice pretreated for 3 days with oil, 5 micrograms/100 g b, wt., or 100 micrograms/100 g b. wt. of estradiol dissolved in oil. Two hours after injection of radiolabeled ligand, brains were frozen and processed for thaw-mount autoradiography. At birth, labeled cells were detected in the deep (lamina VI) and intermediate (lamina V) layers of the lateral cortical regions, increased in laminae V-VI of the lateral cortex and laminae II-VI of the cingulate/paracingulate cortex at days 2 and 8, and decreased throughout the cortex by day 12. Pretreatment of animals with estradiol had no noticeable effect on the nuclear concentration of [125I]progestin in cortical cells, while estrogen weakly enhanced labeling in preoptic/central hypothalamic regions at day 2 and markedly augmented labeling in the 8 and 12 day brain. The results demonstrated that progestin receptor cells are present in the postnatal dorsal cortex, preoptic area, and hypothalamus and that the topography of cortical progestin target cells differs in part from that of estrogen target cells reported earlier. PMID- 1914140 TI - Generation of monoclonal antibodies specific for developmentally regulated antigens of the chicken retina. AB - In order to raise monoclonal antibodies specific for neural antigens that might be involved in regulatory events during histogenesis of the chick visual system, 5 different immunogen fractions were employed in conjunction with 4 immunization regimes. By screening 17,000 hybridoma supernatants from 58 fusion experiments, empirical guidelines were formulated for generation of antibodies with distinct specificities. A number of positive and negative results would not have been predicted from theoretical considerations and emphasize the relevance of empirical data. To substantiate our observations we present 10 monoclonal antibodies that bind to distinct cell types or layers of the retina. Single cell as well as explant cultures in conjunction with Western blot analysis were employed to determine subcellular localization and cell type specificity of selected antibodies. Six antibodies bind specifically to the inner limiting membrane or the optic fiber layer or the inner plexiform layer or the outer plexiform layer. Four recognize selectively ganglion cells or Muller glial cells or presumably subpopulations of amacrine cells. These antibodies promise to be helpful tools to evaluate mechanisms of neural differentiation. PMID- 1914139 TI - Time course of in vitro expression of NADPH-diaphorase in cultured rat brain neurons: comparison with in vivo expression. AB - The time course of NADPH-diaphorase expression was examined in primary cultures of rat central nervous system and in embryonic or neonatal rat brains using a histochemical method. In cerebral and brainstem cultures from 17-day-old embryonic rats, neuronal cells moderately expressing NADPH-diaphorase were first detected on about the 5th to 7th day of culturing. Both the density of positive cells and the staining intensity increased with age of cultures. The density of positive cells, calculated as a percent of the total number of cells, increased up to day 21 in cultures from both the cerebrum and the brainstem, indicating that NADPH-diaphorase is preferentially expressed in neurons with longer viability. On the other hand, virtually no intensely positive cells were detectable in cerebellar cultures at any period examined up to 21 days. In the in vivo study, moderately stained NADPH-diaphorase-positive neurons were first detected, mainly in the laterodorsal-pedunculopontine tegmental nuclei complex and partly in the striatum, in 16-day-old embryonic rat brain. At 2 days postnatal, intensely stained neurons were detectable in the cerebral cortex as well as in the tegmental nuclei complex and the striatum, indicating some delay in the in vitro, as compared to the in vivo, expression of neuronal NADPH diaphorase. PMID- 1914141 TI - Regional cerebral blood flow during hypoxia-ischemia in the immature rat: comparison of iodoantipyrine and iodoamphetamine as radioactive tracers. AB - The indicator fractionation method was used to measure regional cerebral blood flow (rCBF) in immature rats, using either iodo-[14C]antipyrine (IAP) or isopropyl-[14C]iodoamphetamine (IPIA) as the radioisotope. Seven-day postnatal rats received a subcutaneous injection of either IAP (5 microCi) of IPIA (10 microCi), two minutes following which the animals were sacrificed and their brains prepared for quantitative autoradiography. Blood flows to cerebral cortex, hippocampus, striatum, thalamus and hypothalamus were comparable using the two methods, whereas blood flows to white matter structures were substantially higher (+ 64-85%) with IAP. Spatial resolution, especially of the gray matter structures, was greater with IPIA than with IAP. During cerebral hypoxia-ischemia (unilateral common carotid artery ligation and hypoxia with 8% oxygen), blood flows to all regions of the ipsilateral cerebral hemisphere were not different from control at 10 and 20 min. At 1-3 h of hypoxia-ischemia, blood flows were decreased in all analyzed structures of the cerebral hemisphere ipsilateral to the carotid artery occlusion, ranging from 7% to 40% of control values. A columnar or patchy distribution of preferential perfusion was seen within the cerebral cortex, striatum and thalamus, with IPIA, which corresponds closely to the pathologic pattern of injury seen within these structures of the immature rat. Such a preferential perfusion was not seen in hippocampus, in which metabolic factors (intrinsic vulnerability) most likely predict the distribution of hypoxic-ischemic brain damage. PMID- 1914142 TI - Autoradiographic changes in brain adenosine A1 receptors and their coupling to G proteins following seizures in the developing rat. AB - In the central nervous system, adenosine has been shown to be a major regulator of neuronal activity in convulsive disorders, mainly via the A1 receptor subtype. In a previous work, we have shown that seizures lead to an age-dependent upregulation of cerebral adenosine A1 sites measured in isolated rat cerebral membranes. However, information concerning regional changes in the receptor density was so far lacking. In the present study, the effects of bicuculline induced seizures were investigated by quantitative autoradiography of central adenosine A1 receptors in developing rats and in adults. Animals were sacrificed 30 min after an intraperitoneal injection of either saline or a convulsive dose of bicuculline. Adenosine A1 receptors in brain sections were labeled by [3H]N6 cyclohexyladenosine (CHA), a potent receptor agonist. Generalized seizures induced a widespread increase in CHA-specific binding, with a marked enhancement in structures that mediate seizure activity, such as substantia nigra, amygdala, septum and hippocampus. Moreover, the addition of guanylyl-5'-imidodiphosphate, a GTP analogue, to the incubation medium reduced CHA binding by the same order of magnitude whether rats were given saline or bicuculline, suggesting that additional adenosine A1 receptors are also functionally linked to G proteins. The age-related postictal increase in adenosine receptors might contribute to facilitate adenosine anticonvulsant effect, especially in newborns. PMID- 1914144 TI - Effects of cholinergic agonists on immature rat hippocampal neurons. AB - We have investigated the effects of acetylcholine (ACh) and the cholinergic agonist carbachol on several cell types in the developing rat hippocampus. Pyramidal cells were responsive to cholinergic applications on the first day examined (postnatal day 2), indicating that postsynaptic cholinoceptivity develops early, perhaps before functional cholinergic innervation is present. These drugs, which induce a membrane depolarization and a conductance decrease in mature pyramidal cells, had similar effects (both magnitude and pharmacology) on most immature neurons. However, a minority of cells in immature tissue exhibited decreased input resistance (Rin) during the cholinergic-induced depolarization. This response is likely a product of cholinergic action on local circuit neurons: non-pyramidal-type cells from animals as young as 8 days demonstrated excitatory responses to application of cholinergic agonists. The study revealed a number of other features of immature cells which may have functional significance. Lucifer yellow injections showed significant dye coupling among CA3 (but not CA1) pyramidal cells in immature tissue, suggesting close metabolic and/or electrotonic coupling between those cells during development. Mature CA3 cells showed less dye coupling, but increased anomalous rectification, and longer time constant. Developmental changes in intrinsic cell properties, coupled to alterations in local circuit interactions, may alter tissue responsiveness to neurotransmitters such as acetylcholine, even if the receptor-mediated drug action remains stable. PMID- 1914143 TI - Morphine alters astrocyte growth in primary cultures of mouse glial cells: evidence for a direct effect of opiates on neural maturation. AB - To determine whether exogenous opiate drugs with abuse liability directly modify neural growth, the present study investigated the effects of morphine on astrocyte proliferation and differentiation in primary cultures of murine glial cells. The results indicate that morphine decreases glial cell production in a dose-dependent, naloxone-reversible manner. Most notably, gliogenesis virtually ceased in the presence of 10(-6) M morphine during the first week in culture, whereas 10(-8) M or 10(-10) M morphine caused an intermediate suppression of growth compared to control or 10(-6) M morphine treated cultures. Moreover, morphine treatment inhibited [3H]thymidine incorporation by glial fibrillary acidic protein (GFAP) immunoreactive, flat (type 1) astrocytes, suggesting that the decrease in glial cell production was due in part to an inhibition of astrocyte proliferation. Morphine also caused significant increases in both cytoplasmic area and process elaboration in flat (type 1) astrocytes indicating greater morphologic differentiation. In the above experiments, morphine-dependent alterations in astrocyte growth were antagonized by naloxone, indicating that morphine action was mediated by specific opioid receptors. These observations suggest that opiate drugs can directly modify neural growth by influencing two critical developmental events in astrocytes, i.e., inhibiting proliferation and inducing morphologic differentiation. PMID- 1914145 TI - The postnatal emergence of a functional somatosensory representation in the superior colliculus of the mouse. AB - The somatosensory map of the superior colliculus was studied in the mouse during the 2nd and 3rd postnatal weeks, with particular attention to the representation of the vibrissae. The presence of an organized somatosensory projection was not electrophysiologically demonstrable until the beginning of the 3rd postnatal week, in coincidence with the opening of the eyes. Recordings performed during the 2nd postnatal week showed that the collicular units responding to tactile stimuli were rare and functionally immature. Starting from the beginning of the 3rd postnatal week, there was a dramatic increase of the number of somatosensory units and the appearance of an ordered topography, together with the maturation of the neuronal electrical properties. All the features of the adult collicular somatosensory map were found in the 3rd postnatal week, including the magnification of the vibrissae occupying the central portion of the visual field. The functional maturation of the collicular somatosensory map of the mouse is therefore a postnatal event which starts during the 3rd postnatal week, just after the opening of the eyes. PMID- 1914147 TI - Evidence that the relative densities of afferents from both eyes control laminar distribution and binocular segregation of retinotectal projections in rats. AB - In the superior colliculus of normal rodents the crossed retinal projection overlaps the uncrossed projection. The present study describes an abnormal laminar distribution and binocular segregation of the retinotectal afferents induced after the experimental enlargement of the uncrossed retinotectal pathway in pigmented rats. Intraocular injections of anterograde tracers were used to investigate the topographic and laminar organization of retinotectal projections in adult rats given unilateral optic tract lesions at birth. These lesions are known to increase the number of ipsilaterally projecting ganglion cells in the opposite retina. The uncrossed retinal projection to the remaining superior colliculus forms an abnormal band of terminal labeling at the superficial half of the stratum griseum superficiale, markedly different from the laminar distribution of this pathway in unoperated controls. This abnormal uncrossed projection has its maximum density at the rostrolateral quadrant of the tectum. Within this region, the crossed retinotectal projection retracts from the surface of the superior colliculus, leading to partial binocular segregation. The results suggest that both the laminar distribution and the experimental binocular segregation of retinotectal afferents depend on the balance of the densities of the converging pathways from both eyes in the superior colliculus. PMID- 1914146 TI - pH regulation after acid load in primary cultures of mouse astrocytes. AB - Intracellular pH (pHi) recovery in primary cultures of mouse astrocytes after acid-loading was studied with the ion transport inhibitors (amiloride, SITS, acetazolamide, ouabain and bumetanide), and by reducing the concentration of Na+ or Cl- in HCO3- -free HEPES-buffered (HEPES) and in HCO3-/CO2 Hanks' balanced salt solution (HBSS). The pHi of astrocytes exposed to 15 mM NH4Cl decreased abruptly and began to recover slowly after 5 min. Exposure of the cells to NH4Cl for 2 min and reincubation in HEPES HBSS decreased pHi further within 1-2 min after removal of NH4Cl; pHi then recovered toward the control value. Cultures exposed to HCO3-/CO2 HBSS (10 mM/2%) showed changes in pHi in the opposite direction. These responses are unique to astrocytes and differ from those occurring in most other cells. Recovery of pHi after NH4Cl prepulse was markedly inhibited in low-Na+ and in amiloride-containing HEPES HBSS. Ouabain also reduced pHi recovery rate; however, SITS, acetazolamide and bumetanide did not. Therefore, Na(+)-H+ exchange is the major process for pHi recovery from acidification in HCO3- -free solution. In HCO3-/CO2 HBSS pHi recovery was markedly inhibited by SITS and acetazolamide, but not by amiloride, ouabain, or bumetanide. The inhibitory effect of SITS on pHi recovery was enhanced in low-Na+ HBSS. These results indicate that both Na+ and HCO3- are directly related to pHi recovery in HCO3-/CO2 solution after acid-load. Low-Cl HEPES HBSS and low-Cl HCO3 /CO2 HBSS media did not alter pH recovery rate. Thus, pHi recovery after acid load is not Cl- -dependent, and therefore, does not involve a Na(+)-dependent Cl- -HCO3- exchange process. It appears that mouse astrocytes possess 3 acid regulating systems: Na(+)-H+ exchange, Na(+)-HCO3- co-transport and Na(+) independent Cl- -HCO3- exchange. PMID- 1914148 TI - Reduction in the death and cytolamination of developing neurons by tetrodotoxin in the axonal target region. AB - Tetrodotoxin was injected into one eye of chick embryos so as to block activity in the target territory of the isthmo-optic nucleus (ION) during its period of neuronal death. This markedly reduced the neuronal death and thereby prolonged the survival of some 'aberrantly' projecting neurons which would normally all die. In addition, the cytoarchitecture of the ION developed abnormally. Since these two effects differ markedly in their dose-dependence and in other ways, they cannot both be explained by changes in the strength of a single retrograde signal. PMID- 1914149 TI - Evidence for opiate tolerance in newborn rats. AB - It has been reported that tolerance to the antinociceptive effect of morphine does not develop in rats younger than 15 days of age. This may be due to a masking effect of rapidly proliferating opiate receptors during the first 2 postnatal weeks. Newborn rats received morphine (20 mg/kg) or equivolume saline on postnatal days 5, 6, 7, 8 and antinociception was assessed on each day. On day 9, animals of both groups were injected with 0, 0.25, 0.50, 1, 2, 4, 8 or 20 mg/kg of morphine. Antinociception, tested by the tail-flick method, did not diminish over days 5-8, yet on day 9 a rightward shift in the dose-response curve occurred. Thus, tolerance in rats occurs to morphine induced antinociception earlier than 15 days postnatally. PMID- 1914150 TI - Pharmacologically defined M1 and M2 muscarinic cholinergic binding sites in the cat's substantia nigra: development and maturity. AB - Muscarinic cholinergic binding in the substantia nigra of the cat was documented during development and at maturity with autoradiographic methods by labeling the pharmacologically defined M1 and M2 subtypes of muscarinic binding sites. In cats from age embryonic day 40 to postnatal day 6 and at adulthood, M1 sites were labeled with [3H]pirenzepine and M2 sites were labeled with [3H]N methylscopolamine in competition with pirenzepine. Comparisons were made among binding site distributions, acetylcholinesterase staining and tyrosine hydroxylase-like immunoreactivity in serial or neighboring nigral tissue sections. M1 and M2 binding sites were present in the substantia nigra at all ages studied. Qualitative comparisons showed that M1 binding delineated the substantia nigra more distinctly than did M2 binding. For M1 binding sites in particular, the embryonic pars reticulata of the substantia nigra was more prominently labeled than the pars compacta. At adulthood both nigral subdivisions clearly exhibited M1 and M2 binding, with the pars compacta demonstrating some internal heterogeneity of binding density. These findings provide further evidence that the substantia nigra is a site of cholinergic transmission and suggest that the functional balance between acetylcholine and dopamine in the basal ganglia acts here as well as in the striatum. PMID- 1914151 TI - Distribution of estrogen target sites in the 2-day-old mouse forebrain and pituitary gland during the 'critical period' of sexual differentiation. AB - The present study provides a detailed anatomical description of estrogen target cells in the mouse forebrain and pituitary gland during the sexual imprinting stage of the brain. Six 2-day-old mice (3 males and 3 females) were s.c. injected with 16 alpha-[125I]iodo-11 beta-methoxy-17 beta-estradiol ([125I]MIE2) and two additional mice (one male and one female) were s.c. injected with 1000x unlabeled 17 beta-estradiol 1 h before [125I]MIE2 to check the specificity of estradiol binding. Two hours after injection the mice were decapitated, the brains dissected, frozen sectioned, and processed for thaw mount autoradiography. The highest intensity of nuclear labeling was observed in the preoptic-anterior hypothalamic area, amygdala and cortex entorhinalis. Strong labeling was present in the cerebral cortex and moderate to strong labeling in the lateral septum, bed nucleus of stria terminalis and pituitary gland. Weak to moderate labeling was observed in the bulbus olfactorius, circumventricular organs, basal ganglia, ventral striatum, thalamus, hippocampus and pineal gland. No sex differences were observed in the intensity of labeling and distribution of the estrogen target sites. The topographic distributions of estrogen-concentrating cells in the hypothalamus of the 2-day-old mouse forebrain was similar to the adult pattern but differed prominently in the cerebral cortex, entorhinal cortex and thalamus: the cerebral cortex showed an extensive and intensive labeling, the intensity of labeling in the entorhinal cortex greatly exceeded that observed in the adult and the nucleus anterior medialis thalami was distinctly labeled. PMID- 1914152 TI - Autoradiographic localization of adenosine A1 receptors in brainstem of fetal sheep. AB - Quantitative autoradiographic techniques were used to localize adenosine A1 receptors at the light microscopic level with the antagonist [3H]8-cyclopentyl 1,3-dipropylxanthine [( 3H]DPCPX) in the brainstem of fetal sheep. Since adenosine has been proposed as a neuromodulator, which effects the depression of fetal breathing movements during hypoxia, attention was directed to respiratory neuronal areas. The highest density of A1 receptors in respiratory related groups was found in an area of the rostral ventrolateral medulla, which is ventral to the facial nucleus, caudal to the superior olive and lateral to the rostral inferior olive. Intermediate densities were seen in the medial and lateral parabrachial nuclei. Adenosine A1 receptor density was low in the areas of the nucleus of the solitary tract and the nucleus ambiguous. These data suggest that moderate hypoxia in the fetus may depress respiration by withdrawing a tonic stimulus at the level of the ventral lateral medullary chemoreceptors. PMID- 1914153 TI - Synaptic 5'-nucleotidase is transient and indicative of climbing fiber plasticity during the postnatal development of rat cerebellum. AB - The transient appearance of 5'-nucleotidase, an adenosine-producing ecto-enzyme, was studied during specific stages of postnatal synaptogenesis in the rat cerebellum. For ultrastructural detection of 5'-nucleotidase activity, an enzyme cytochemical technique was used. Between postnatal days 4 and 6, enzymatic reaction product was present in the synaptic clefts of climbing fibers containing the perisomatic spines, apical cones and emerging dendrites of Purkinje cells (CF PC synapses). Labeled parallel fiber synapses were observed on dendritic shafts of cerebellar interneurons. At postnatal days 9 and 12, enzyme-positive parallel fiber terminals were in addition numerous on the spines of peripheral Purkinje branchlets, and gradually disappeared thereafter. Between postnatal days 8 and 15, labeling of perisomatic CF-PC contacts persisted. In contrast, climbing fiber synapses on Purkinje dendrites were only occasionally labeled. Between postnatal days 18 and 21, synaptic reaction product was restricted to mossy fibers. At the same time, association of 5'-nucleotidase with glial profiles was prominent throughout the cerebellar layers. In adult cerebellum (from 24 days onwards) all synapses were devoid of enzymatic activity. Throughout development, basket, stellate and Golgi cell synapses were devoid of enzymatic activity. We conclude that 5'-nucleotidase is present in excitatory cerebellar synapses during part of their generation period. The transient nature of this phenomenon suggests that 5' nucleotidase may serve as a novel, cytochemical marker for a specific state of synaptic maturation, and in particular for climbing fiber plasticity. A role of 5'-nucleotidase in purinergic neuromodulation and cellular contact formation could be significant in these processes. PMID- 1914154 TI - Cerebellar reaggregate and explant transplants contain Bergmann glial fibers. AB - In mammalian cerebellum, granule cells are believed to migrate from the external germinal layer to the internal granular layer on radially oriented arrays of Bergmann glial fibers. It has been shown that similar arrays of Bergmann fibers are present in intact cerebellar transplants in rats. In the present study radial, parallel arrays have been observed in reaggregate and explant transplants in rats. These findings are consistent with the hypothesis that Bergmann fibers are involved in migration of granule cells and/or other aspects of formation of the trilaminar cortical pattern in cerebellar transplants. PMID- 1914155 TI - Differential effects of neonatal castration on the development of sexually dimorphic brain areas in the gerbil. AB - We compared the effects of neonatal castration within 6 h of birth in the Mongolian gerbil on the development of the sexually dimorphic area pars compacta (SDApc) and supraschiasmatic nucleus (SCN). Development of these brain areas was also related to a masculine courtship ultrasonic vocalization, the frequency modulated upsweep. Castration immediately after birth resulted in differential effects with complete or partial reduction of SCN and SDApc volumes, respectively, as compared to male values. The rates of ultrasonic calling of males castrated as neonates were also decreased to female levels. In sham operated males, calling rates were positively correlated with the volume of the left SDApc, but not the right. Both the left and the right SDApc volumes were correlated with calling rates in males castrated as neonates. The asymmetric relationship between vocal behavior and area volume was specific to the SDApc. We suggest that in the neonate (a) the sensitivity of the SDApc to the differentiating effects of androgens differs from the SCN and (b) the asymmetric link between brain structure and vocal behavior depends on the effects of androgen within 6 h of birth. PMID- 1914156 TI - Ontogenetic and seasonal changes in immunoreactive vasotocin in the canary brain. AB - Using immunocytochemistry the central VT system of the canary was examined during ontogeny and throughout the season. At 4 weeks of age no VT-immunoreactive staining in the bed nucleus of the stria terminalis and lateral septum was present, but VT-containing cells and fibers were clearly visible in the nucleus paraventricularis of the hypothalamus. At 13 weeks of age a weak VT immunoreactivity appeared in the bed nucleus of the stria terminalis and lateral septum. This VT immunostaining increased progressively till at the age of 28 weeks adult levels were reached. In adulthood, cells and fibers in the lateral septum and the bed nucleus of the stria terminalis contained the highest amounts of immunoreactive VT during the breeding season, whereas during the molt, in august, a decreased VT immunostaining was noted. These seasonal changes in VT immunostaining coincided with variations in circulating testosterone level, which is high during the breeding season and low during the molt. In the ventral capsular region surrounding the nucleus robustus archistriatalis a clear VT immunoreactive fiber pattern was demonstrated at the age of 8 and 13 weeks in both female and male canaries. Although the size of this nucleus varies during the season no seasonal changes in the VT-immunoreactive pattern surrounding the RA were detected. The data suggest that the activity of the VT system slowly increases during development. At adulthood seasonal and gonadal hormone-dependent changes occur in the limbic VT system only. The VT immunostaining associated with the nucleus robustus archistriatalis however, is resistant to seasonal and gonadal influences. PMID- 1914158 TI - Local cerebral blood flow response to locally infused 2-chloroadenosine during hypotension in piglets. AB - Brain interstitial adenosine increases during hypotension in piglets. If adenosine is to participate in the regulation of neonatal cerebral blood flow (CBF) during hypotension, it must retain its vasodilatory action under that condition. To examine this issue, we studied the effects of locally infused 2 chloroadenosine (2-CADO), a stable adenosine analog, on local CBF in the piglet frontal cortex during normotension and graded hemorrhagic hypotension. We used the modified brain microdialysis/hydrogen clearance technique to simultaneously infuse 2-CADO into the frontal cortex and measure local CBF from the same area. When 2-CADO from 10(-8) M to 10(-3) M was infused under control conditions (n = 7), CBF increased 61% at 10(-5) M, 167% at 10(-4) M, and 210% at 10(-3) M. In hypotension experiments, local infusion of 10(-5) M 2-CADO (n = 8) caused significant increases in CBF (P less than 0.05) under control conditions (MABP = 65 mmHg) and at hypotensive blood pressures of 55 mmHg and 44 mmHg, respectively. At a blood pressure of 33 mmHg, however, infusion of the analog failed to increase CBF. Local infusion of 10(-3) M 2-CADO also produced a similar change in CBF during graded hypotension. These results indicate that 2-CADO dilates intracerebral vessels during normotension, and mild and moderate hypotension, and support the hypothesis that endogenous adenosine mediates autoregulatory adjustments of CBF during hypotension in newborn piglets. PMID- 1914157 TI - Postnatal development of ganglion cells in the rabbit retina: characterizations with AB5 and GABA antibodies. AB - The use of cell-specific monoclonal antibodies provides a means by which the emergence, differentiation and maturation of retinal neurons can be studied. The present study investigates the labelling of ganglion cells in the developing rabbit retina by a ganglion cell-specific monoclonal antibody, AB5(12,13). AB5 labelling of ganglion cells was observed as early as day postnatal. By 6-8 days postnatal, AB5-labelled ganglion cells had begun differentiating into the various ganglion cell subtypes observed in the adult retina. This differentiation process appeared to continue throughout the first 3 weeks postnatal. The AB5 monoclonal antibody was also used in a double-label paradigm with an anti-gamma-aminobutyric acid (GABA) polyclonal antibody to differentiate the GABAergic ganglion cells from other GABAergic elements in the retina and to study their development. GABAergic ganglion cells were first observed at 3 days postnatal and by 6 days postnatal, it was possible to observe a wide variety of GABAergic ganglion cells ranging from small cells to large alpha-type cells. The appearance of AB5 labelling in ganglion cells at relatively early stages of development suggests that the AB5 monoclonal antibody may be a useful tool for studying the development of ganglion cell structure, distribution, synaptic relationships and neurochemical specificity. PMID- 1914159 TI - An ontogenetic study of kindling using rapidly recurring hippocampal seizures. AB - The present study investigated the acquisition and retention of kindling in immature rats. Postnatal (PN) 7-28-day-old rats were electrically kindled in the ventral hippocampus. Ten-second, 20-Hz stimulus trains were delivered every 5 min for 6 h on one day (short interval rapidly recurring hippocampal seizures, RRHS) or every 30 min for 9 h on each of two consecutive days (long interval RRHS). Afterdischarge durations (ADD) and behavioral seizure scores (BSS) were recorded following each stimulation. Animals of all ages kindled with both short and long interval RRHS, as manifested by lengthening of ADD and increasing BSS. With short interval RRHS, the course of kindling was erratic; with long interval RRHS, kindling proceeded smoothly over both test days. In PN 14-28 rats, the degree of kindling obtained on the first day of long interval RRHS was retained at the start of the second experimental day. In contrast, PN 7 rats showed a transient decrease in ADD and BSS from day 1 to day 2. Afterdischarge thresholds declined with maturation. Among the PN 14-28 animals, younger rats exhibited longer seizures at the outset of kindling and proceeded through kindling faster. Once established, kindled motor seizures also occurred with 2-s, 50-Hz stimulus trains. We conclude that rapid kindling occurs at all ages; however, PN 7 rats are less capable of retaining the kindling effect than are older rats. PMID- 1914161 TI - Clinical chemistry analyte reference systems based on true value. PMID- 1914162 TI - Serological diagnosis with recombinant peptides/proteins. PMID- 1914160 TI - Corticotropin-releasing hormone is a rapid and potent convulsant in the infant rat. AB - Corticotropin-releasing hormone (CRH) administered into the cerebral ventricles of rats during the first postnatal week caused a specific and stereotyped behavior sequence: rhythmic chewing and licking (jaw myoclonus) were followed by 'limbic'-type seizures. The onset of the seizures was much more rapid (2-45 min vs 3-7 h) than in adult rats, and the convulsant doses were much lower (50 x 10( 12) mol per gram brain weight vs 750 x 10(-12) mol per gram brain weight in adults). CRH potency in inducing seizures varied inversely with age. CRH-induced seizures occurred prior to any changes in serum corticosterone, and were eliminated by the administration of a CRH antagonist, as well as of phenytoin. Electrocorticographic correlates of CRH-induced behaviors in the infant rat were inconsistent, suggesting a subcortical origin of CRH-induced paroxysmal events in the immature brain. PMID- 1914163 TI - HPLC with enzymatic detection as a candidate reference method for serum creatinine. AB - We present a candidate Reference Method for determining the concentration of serum creatinine. The method is based on HPLC combined with enzymatic determination. Creatinine plus 14[C]creatinine is extracted by cation-exchange chromatography, subjected to reversed-phase HPLC, and finally quantified enzymatically. Enzymatic measurement ensures no interference from co-eluting compounds, which has been a problem for some reported HPLC assays relying on ultraviolet detection. The average corrected recovery was 100.1% (SEM = 1.1%; n = 15). The accuracy was verified by assaying five sera with target values determined by isotope dilution mass spectrometry. The total interassay CV was less than or equal to 2.5%. We applied the method to study the specificity of HPLC-ultraviolet detection, using 72 plasma samples from hospitalized patients; no interference was noted. Thus, HPLC-ultraviolet detection appears to be specific, provided that sample cleanup is based on cation-exchange chromatography. Our diode-array detector studies of peak homogeneity supported this conclusion. Still, combined HPLC-enzymatic determination ensures even greater accuracy, ranking close to that by isotope dilution mass spectrometry. PMID- 1914164 TI - International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. AB - To minimize differences in apolipoprotein measurements among laboratories and methods, a standardization program involving common suitable reference material is needed. The Committee on Apolipoproteins of the International Federation of Clinical Chemistry initiated a collaborative study for the standardization of test systems for measuring apolipoproteins (apo) A-I and B, with 25 company laboratories and three research laboratories involved in apolipoprotein analysis to: (a) evaluate calibration differences among the test systems; (b) evaluate whether comparability of the data can be achieved with the use of frozen serum pools to recalibrate the different systems; and (c) evaluate and select suitable candidate reference material. We used 26 test systems for apo A-I and 28 for apo B. Relatively modest differences were found in calibration for apo A-I, but very wide differences were observed for apo B methods. After uniform calibration, the overall among-laboratory CV for apo B decreased from 19% to 6%. Three lyophilized serum preparations for apo A-I and three liquid-stabilized serum preparations for apo B were selected for further evaluation as candidate international reference materials. PMID- 1914165 TI - Determination of silver in blood, urine, and tissues of volunteers and burn patients. AB - Silver sulfadiazine cream (SSD) has been used successfully in the management of burn wound sepsis. Silver deposition has been found in the skin, gingiva, cornea, liver, and kidney of patients treated with this cream, causing argyria, ocular injury, leukopenia, and toxicity in kidney, liver, and neurologic tissues. Monitoring concentrations of silver in blood and urine of patients receiving this treatment has become necessary, but sensitive and suitable methods adaptable to a clinical laboratory are still needed. We have developed a flameless thermal atomic absorption spectrophotometric method to measure silver concentrations in blood, urine, and other tissues. The detection limit is 0.4 microgram/L; the within-run precisions (CV) are 5.16%, 3.83%, and 2.79% for concentrations of 5, 13.5, and 42 micrograms/L, respectively; and the between-run precisions are 4.3% and 3.2% for concentrations of 13.5 and 42 micrograms/L. The concentrations of silver in blood, urine, liver, and kidney of subjects without industrial or medicinal exposure are less than 2.3 micrograms/L, 2 micrograms/day, 0.05 microgram/g wet tissue, and 0.05 microgram/g wet tissue, respectively. In SSD cream-treated burn patients, plasma concentrations may be as great as 50 micrograms/L within 6 h of treatment and can reach a maximum of 310 micrograms/L. Silver in urine is detectable after one day of treatment and may reach a maximum of 400 micrograms/day. After absorption, silver was found to be deposited in various tissues. Tissue silver concentrations in one burn patient who died of renal failure after eight days of treatment were 970, 14, and 0.2 micrograms/g wet tissue in cornea, liver, and kidney, respectively. PMID- 1914166 TI - Indocyanine green-sulfobromophthalein pharmacokinetics for diagnosing primary biliary cirrhosis and assessing histological severity. AB - Primary biliary cirrhosis (PBC) is a chronic cholestatic disease in which there is a crucial need for quantitative liver-function tests. We have developed a mixed sulfobromophthalein (BSP)-indocyanine green (ICG) test and have applied it to 15 healthy subjects and 50 patients with PBC to determine its relevance to the histological severity of the disease. The two dyes were administered intravenously and sequentially as boluses. Plasma concentrations were measured over 60 min. Pharmacokinetic analysis of the plasma elimination curve permitted the calculation of clearance, constants k1 and k2, and the retention percentage at 45 min. In PBC patients, ICG kinetics were within the normal range except for those with stage IV disease (cirrhosis). BSP clearance and the k2 constant were reduced in all the patients, whereas the k1 constant was reduced only in stage III and IV disease. The BSP retention percentage at 45 min was highly correlated with histological stage (r = 0.89, P less than 0.001). The BSP-ICG mixed test may thus prove useful in the diagnosis and follow-up of patients with PBC. PMID- 1914167 TI - Radioimmunoassay of interleukin-6 in plasma. AB - We present a double-antibody radioimmunoassay for determining human interleukin-6 (IL-6) in biological fluids. The detection limit of the assay is 20 ng/L (B0 - 2 SD). Bound radioactivity in the range of 30% to 90% of the B0 counts corresponds to IL-6 concentrations of 100 to 14,000 ng/L. Analytical recovery of IL-6 added to EDTA-treated plasma averaged 25% more than that added to serum. The plasma concentration of IL-6 was therefore approximately 85 ng/L more than the concentration in simultaneously drawn serum. The mean serum concentration of IL-6 in 45 healthy subjects was 83 ng/L (range 20-290 ng/L), in 20 patients with multiple myeloma 303 ng/L, in 20 patients with rheumatoid arthritis 234 ng/L, and in 13 patients with systemic lupus erythematosus 183 ng/L. Markedly increased (greater than 3000 ng/L) concentrations of IL-6 were found in sera of patients with meningococcus meningitis and infectious peritonitis. PMID- 1914168 TI - Association between urinary N-acetyl-beta-glucosaminidase and its isoenzyme patterns and microangiopathy in type 1 diabetes mellitus. AB - Urinary N-acetyl-beta-glucosaminidase (NAG) and its isoenzymes (NAG A and NAG B) in samples from 87 type 1 diabetic patients and 40 apparently healthy reference subjects were studied with enzyme immunoassays. The diabetic patients had higher concentrations of urinary NAG than did the control subjects (P less than 0.01), but the isoenzyme pattern did not differ. There was a positive correlation between metabolic control (Hb A1c concentrations) and total NAG (P less than 0.01), NAG A (P less than 0.01), and NAG B (P less than 0.001). The diabetic patients were divided into three groups, depending on the degree of retinopathy. Subjects with severe forms of retinopathy did not have increased concentrations of urinary NAG unless they had concomitant nephropathy. The isoenzyme pattern was similar irrespective of degree of retinopathy or nephropathy. The results indicate that concentrations of urinary NAG are positively correlated to the degree of nephropathy, whereas there is no such correlation to the degree of retinopathy. PMID- 1914169 TI - Confirmation and differentiation of antibodies to human immunodeficiency virus 1 and 2 with a strip-based assay including recombinant antigens and synthetic peptides. AB - We evaluated the use of the INNO-LIA HIV-1/HIV-2 Ab test (LIA HIV; Innogenetics) for the confirmation of antibodies to human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). The test includes three recombinant HIV-1 proteins: p24 (gag), p17 (gag), and endonuclease (p31; pol), in combination with two synthetic peptides derived from the env gene of HIV-1 and one synthetic peptide selected from the env gene of HIV-2. Analysis of 450 sera from blood donors, 220 sera from patients with non-HIV pathology, and 28 Western blot (WB) p24-only reactive sera revealed no false-positive results, and the rate of indeterminate results was substantially lower than that with WB. Testing of 334 WB-confirmed HIV antibody positive sera (309 HIV-1; 25 HIV-2) revealed no false-negative results. In two of seven seroconversion panels tested, LIA HIV detected the presence of HIV antibodies before WB did. In the other five panels, LIA HIV and WB confirmed the presence of HIV antibodies in the same sample. The LIA HIV assay therefore appears well suited for routine confirmation of the presence of HIV-1 and HIV-2 antibodies. PMID- 1914171 TI - Estimating the performance characteristics of quality-control procedures when error persists until detection. AB - The concepts of the power function for a quality-control rule, the error detection rate, and the false rejection rate were major advances in evaluating the performance characteristics of quality-control procedures. Most early articles published in this area evaluated the performance characteristics of quality-control rules with the assumption that an intermittent error condition occurred only within the current run, as opposed to a persistent error that continued until detection. Difficulties occur when current simulation methods are applied to the persistent error case. Here, I examine these difficulties and propose an alternative method that handles persistent error conditions effectively when evaluating and quantifying the performance characteristics of a quality-control rule. PMID- 1914170 TI - Glucocorticoid receptors in normal leukocytes: effects of age, gender, season, and plasma cortisol concentrations. AB - We measured glucocorticoid receptors (GR) in mononuclear leukocytes (MNL) isolated from peripheral blood of 145 apparently healthy volunteers (86 men and 59 women). An age-related decrease in the number of GR was suggested between subjects younger than 20 years and elderly subjects; there was no apparent seasonal variation in GR. Gender difference in the number of GR was not significant, although women showed slightly fewer GR. Eight patients with dermatomyositis/polymyositis were examined to determine whether the number of GR in MNL could be down-regulated by their cognate ligands. The number of GR in MNL from these patients was significantly decreased one month after the initiation of prednisolone therapy. However, in normal subjects, the GR in MNL did not demonstrate circadian variation, in contrast to concentrations of plasma cortisol. PMID- 1914172 TI - Interlaboratory comparison of glycohemoglobin results: College of American Pathologists Survey data. AB - We describe recent changes in the College of American Pathologists Glycohemoglobin (gHb) Survey, made to improve the assessment of interlaboratory variability and the accuracy of results reported. The questionnaire portion of the survey was revised to include an updated list of current methods, and results for survey specimens were grouped according to the component measured (Hb A1, Hb A1c, or total gHb). The survey specimen material was changed to a material thought to give more reliable results with all available methods. After these changes, instituted in 1989, between-laboratory CVs decreased for some methods. Furthermore, gHb values between method types were more consistent with results obtained from fresh blood samples under very controlled laboratory conditions. However, these recent data also show that the interlaboratory variability is still quite high for some methods and that the variability within and between method types is still very great. We describe a pilot standardization program for gHb measurement. PMID- 1914173 TI - Dry electrolyte-balanced heparinized syringes evaluated for determining ionized calcium and other electrolytes in whole blood. AB - By analyzing whole blood containing no anticoagulants (uncoagulated whole blood) immediately after collection, we evaluated the relative changes in the concentrations of ionized calcium and other electrolytes in whole blood collected in dry heparinized syringes and in serum prepared from blood collected in evacuated blood-collection tubes. Using these dry heparinized syringes, we collected and analyzed whole blood that contained either 33 or 13 int. units of lithium heparin or 40 int. units of electrolyte-balanced heparin per milliliter of blood. We evaluated the effects both of these heparins at different concentrations of ionized calcium and of the incomplete filling of the syringes. We conclude that: (a) when analyzed within 2-3 min after collection, uncoagulated whole blood provides ionized calcium results unaffected by anticoagulants or cellular metabolism; (b) the preparation of serum unpredictably changes ionized calcium; (c) the use of dry electrolyte-balanced heparin virtually eliminates the interference in ionized calcium concentrations between 0.9 and 1.6 mmol/L; and (d) incomplete filling of electrolyte-balanced heparinized syringes produces no effect in syringes two-thirds full (60 int. units/mL heparin concentration) and a small effect in syringes one-third full (120 int. units/mL heparin). PMID- 1914174 TI - Enzymatic method for measuring ethylene glycol with a centrifugal analyzer. AB - We describe a semiautomated, enzymatic method of analysis for ethylene glycol in plasma. Glycerol dehydrogenase (EC 1.1.1.6) from Enterobacter aerogenes, which has high specificity for ethylene glycol, is mixed with 3 microL of specimen in a centrifugal analyzer. NAD+ is added to initiate the reaction, and 450 s after an initial 90-s delay, the absorbance at 340 nm is measured. Monthly calibration with a five-point calibration curve is sufficient to provide between-day precision (CV) of 2% to 5%. The detection limit is 0.3 mmol/L with a CV of 10%. There is no significant interference from ethanol, methanol, isopropanol, acetone, lactate, or glycerol. PMID- 1914175 TI - Major disagreements between immunoassays of carcinoembryonic antigen may be caused by nonspecific cross-reacting antigen 2 (NCA-2). AB - Four "sandwich"-type immunoassays of carcinoembryonic antigen (CEA) based on the use of monoclonal antibodies (Abbott CEA-RIA Monoclonal, Pharmacia/Wallac Delfia CEA kit, Roche CEA EIA Duomab 60, and our in-house immunoradiometric assay) were tested for cross-reaction with nonspecific cross-reacting antigen 2 (NCA-2) in meconium. The Roche assay did not react with NCA-2, but the other three assays cross-reacted strongly and to about the same extent with this antigen. NCA-2 is the CEA gene family member that is structurally most similar to CEA, and other authors have found by indirect evidence that this antigen also is increased in the serum of many cancer patients. In a previous study we found that the Roche assay yielded lower mean values than the other assays for CEA in serum from colorectal cancer patients. Furthermore, the correlation between the Roche CEA values and those of each of the other three assays was weaker than the correlation between these NCA-2 cross-reactive assays. We conclude that these results can be explained by the different cross-reactivity with NCA-2 of the antibodies used by the various assays, as described here. Our findings raise interesting questions regarding the possible role of NCA-2 as a tumor marker. PMID- 1914177 TI - Quantification of serum amyloid P by enzyme-linked immunosorbent assay. AB - This enzyme-linked immunosorbent assay procedure for quantifying serum amyloid P (SAP) in human plasma makes use of affinity-purified polyclonal antibodies to SAP in a "sandwich"-type format. The procedure is sensitive, reproducible, simple, and easily automatable. Results correlate well with those by a rocket immunoelectrophoresis method performed with the same antibodies. Sera from apparently normal individuals had a mean SAP content of 44.17 mg/L and increased with age. PMID- 1914176 TI - Microtechnique for quantifying phenol in plasma by gas chromatography-mass spectrometry. AB - Methods for detection and quantification of phenol have been developed primarily for use in environmental and industrial monitoring, given the widespread use of phenol as a disinfectant and antiseptic. Little information is available regarding concentrations of phenol in the blood of patients treated with phenol in regional nerve blocks (e.g., intrathecal) for temporary relief of pain or spasticity. We report a specific and sensitive method for quantifying phenol in plasma, using chemical derivatization and high-resolution capillary column gas chromatography in conjunction with mass spectrometry. The assay we describe was developed to monitor plasma concentrations of phenol in children given motor point nerve blocks with dilute phenol. PMID- 1914178 TI - Monoclonal antibody-based discrepancies between two-site immunometric tests for lutropin. AB - We compared five two-site immunometric assays (including three commercially available kits) for measuring lutropin (LH) in serum. Four of the assays involved monoclonal antibodies directed against the alpha-beta dimer, intact LH; these assays measured significantly lower concentrations of LH in 19 (out of 83) samples than did a commercial method not involving such antibodies. In five serum samples, two of the intact LH assays failed to detect any significant immunoreactivity above the detection limit. Findings of normal in vitro LH bioactivity in these samples did not confirm the low immunoreactivity of the intact LH assays. The inability of these assays to detect bioactive LH creates confusion in daily, routine testing as well as in research monitoring of bio/immuno ratios. The data presented here confirm our previous findings (Clin Chem 1991;37:333-40) and emphasize the need to avoid the use of monoclonal antibodies specific for the intact LH dimer. PMID- 1914179 TI - Six methods for direct radioiodination of mouse epidermal growth factor compared: effect of nonequivalence in binding behavior between labeled and unlabeled ligand. AB - Mouse epidermal growth factor (EGF) was radioiodinated by six different direct iodination methods. The 125I-labeled EGF preparations were distinguished by analyzing the binding of the radioligand to the EGF receptor (EGFR)-containing human placental membranes. The receptor-binding affinity of EGF labeled with Chloramine T was less than the affinity of unlabeled EGF, which precluded an accurate determination of the specific radioactivity of the 125I-labeled EGF preparation by "self-displacement analysis." Scatchard analysis of competitive binding data (increasing concentrations of unlabeled EGF) obtained with commercially prepared 125I-labeled EGF (Chloramine T method), according to the specific radioactivity stated by the manufacturer, resulted in a substantial underestimation of the apparent number of receptors. Iodination of EGF with Iodogen or Iodo-beads, reagents claimed to be more gentle because of their solid state, also yielded 125I-labeled EGF preparations that were not equivalent to the native EGF in receptor binding. In contrast, equivalence in the ligand-receptor interaction between labeled and unlabeled EGF could be achieved by iodinating EGF with iodine monochloride (ICl), Protag-125, or lactoperoxidase-glucose oxidase coupled beads (Enzymobeads). Scatchard plots of saturation and competitive binding data obtained with these 125I-labeled EGF preparations produced identical results for apparent receptor number and apparent dissociation constants. Such radioiodinated EGF preparations yield relevant binding data in competition studies of labeled and unlabeled EGF. PMID- 1914180 TI - Plasma lipoprotein peroxidation potential: a test to evaluate individual susceptibility to peroxidation. AB - Peroxidation of lipids is believed to play a key role in various degenerative diseases. However, few simple tests are able to detect individual susceptibility or resistance to peroxidation. Measurement of the basal concentrations of lipid peroxides in plasma is not satisfactory because they are so low. Therefore, we developed a test to determine susceptibility of whole plasma to metal/H2O2 catalyzed peroxidation. Incubation of 300-500 microL of plasma with H2O2/cupric acetate resulted in the formation of products from fatty acids (malonaldehyde, measured by thiobarbituric acid assay) and cholesterol (predominantly cholest-3,5 dien-7-one, measured by gas-liquid chromatography). In the presence of Cu2+, formation of malonaldehyde and cholest-3,5-dien-7-one increased at least 10-fold over basal values. Lipid peroxide (malonaldehyde) and cholesterol oxide concentrations after peroxidation were significantly higher (P less than 0.01) in diabetic plasma than in normal plasma. Because susceptibility to plasma peroxidation represents a balance between pro-oxidant factors and antioxidant protection, this test may be useful in determining individual susceptibility to peroxidation as influenced by nutritional and clinical status. PMID- 1914182 TI - Measuring rheumatoid factor in nonrheumatoid subjects: immunoturbidimetric assay, latex slide test, and enzyme-linked immunosorbent assay compared. AB - Previous studies of patients with rheumatoid arthritis (RA) have shown a good correlation between results from immunoturbidimetric assays of rheumatoid factor (RF) and latex fixation tests. To extend the research to non-RA subjects, we tested sera from 1000 pregnant women, half each in the first and third trimesters. By turbidimetry, 24 non-RA sera were regarded as positive for RF (greater than or equal to 20 int. units/mL) and 18 sera as borderline (15-19 int. units/mL). By the latex fixation test, 28 non-RA sera gave a clear reaction (positive) and 17 sera a weak reaction (borderline). The association between the tests was statistically highly significant (P less than 0.001). All sera with positive and borderline reactions were tested by enzyme-linked immunosorbent assay for RF isotypes, together with a random subsample of about one-sixth of the original serum samples. Positive RF results by immunoturbidimetry were predominantly due to the presence of IgM-RF. In contrast to some earlier findings, we saw no difference in the prevalence of positive RF reactions between sera from the first and third trimesters. PMID- 1914181 TI - Immunoradiometric assay of pS2 protein in breast cancer cytosols. AB - We studied the ELSA-pS2 immunoradiometric kit (CIS Bio International) for pS2 protein assay in breast cancer cytosols according to classic validation methods. In addition, we studied correlations between pS2, steroid receptors, and cathepsin-D assays. Repeatability (CV = 1.5% to 4.8%) and reproducibility (CV = 1.6% to 4.9%) were good. The results were linearly related to pS2 concentrations between 205 and 2200 ng/L; the detection limit was 40 ng/L. The accuracy of the assay was measured by assessing recovery; analytical recoveries were near 100% throughout the standard curve. The use of different compounds for cytosol preparation (Tris 10 mmol/L or phosphate 25 mmol/L, KCl 0.4 mol/L, bovine serum albumin 1 g/L) had no effect on pS2 results. pS2 was assayed in breast tumor cytosols from 197 postmenopausal and 92 premenopausal patients. The mean value was 24 micrograms/g of protein; the median and 25th and 75th percentiles were 6, 1, and 23 micrograms/g protein, respectively. We observed a relation between concentrations of pS2 and those of estrogen and progesterone receptors, but there was no relationship between the concentrations of pS2 and cathepsin-D. PMID- 1914183 TI - Pentobarbital quantification in the presence of phenobarbital by fluorescence polarization immunoassay. AB - We developed a method for measuring pentobarbital in samples that also contain phenobarbital. The phenobarbital is destroyed by adding sodium hydroxide and then heating at 95 degrees C for 60 min. Pentobarbital is not affected by this pretreatment and can then be measured with an Abbott TDx barbiturates kit. Using this method, we obtained an average analytical recovery of 98% of added pentobarbital and a correlation of y = 0.953x + 3.4 vs HPLC. The intra-assay CV was 3.7% at 25.8 mg/L; the interassay CV was 6.2% at 16.1 mg/L. Other long-acting barbiturates, e.g., hexobarbital, are also effectively destroyed by this alkali pretreatment. Other short-acting barbiturates, e.g., secobarbital, are not removed and would produce an interference. PMID- 1914184 TI - Comparison of thyroperoxidase and microsomal antibody assays in sera from patients with Graves disease. AB - Anti-microsomal (anti-Mic Ab) and anti-thyroperoxidase antibody activities (anti TPO Ab) were compared by using commercially available radioassay kits. Sera were collected from 52 patients with Graves disease before and after administration of carbimazole (1-methyl-2-thio-3-carbethoxyimidazole). The two antibody concentrations were significantly correlated, both before treatment (r = 0.835, P less than 0.001, n = 52) and at the end of treatment (r = 0.584, P less than 0.001, n = 52). Twenty-nine (Group I) of the 52 patients were in remission for two years after drug withdrawal, whereas 23 (Group II) relapsed. Within each group, the anti-Mic and anti-TPO Ab concentrations were significantly correlated (Group I: r = 0.781, P less than 0.0001; Group II: r = 0.866, P less than 0.0001). Relapse vs nonrelapse was linked to the antibody positivities measured before treatment: 91% vs 65% (chi 2 = 4.75, P less than 0.02) for anti-Mic Ab and 87% vs 62% (chi 2 = 4.05, P less than 0.02) for anti-TPO Ab. We conclude that assays of anti-Mic and anti-TPO Ab are equally reliable analytically and equally informative clinically. Because of its rapid implementation, the anti-TPO assay may advantageously replace anti-Mic Ab assay, especially for forming a prognosis of Graves disease. PMID- 1914185 TI - Polyclonal gammopathy with marked increase in serum viscosity. AB - A 45-year-old man with polyclonal hypergammaglobulinemia (gamma globulins, 102 g/L) had a serum relative viscosity of 13 nu but did not manifest clinical signs of hyperviscosity syndrome (e.g., retinopathy, bleeding diathesis, and neurological alterations), except for fatigue and anorexia. In contrast with other patients with polyclonal hyperviscosity reported so far, this patient did not have detectable rheumatoid factor in serum. Analytical ultracentrifugation of his serum showed aggregates of polyclonal IgG3 of various sizes (between 10 and 36 S). The serum also contained immune complex-like material, as demonstrated by the Raji cell immunoradiometric assay and the C1q solid-phase enzyme immunoassay. PMID- 1914186 TI - Biological variation of urinary magnesium. PMID- 1914187 TI - Neonatal hypothyroidism screening with immunochemiluminometric assay of thyrotropin. PMID- 1914188 TI - Enhancing interpretive test reporting: clinical chemists' unsettled perspective. PMID- 1914189 TI - Who is still a clinical chemist? PMID- 1914190 TI - Fluorescein interference with urinary creatinine and protein measurements. PMID- 1914191 TI - Utility of serum phospholipase A measurements. PMID- 1914192 TI - Excess serum osmolality after ingestion of methanol: the exception, not the rule. PMID- 1914193 TI - Colorimetric reagent for assay of urea. PMID- 1914194 TI - Presence of "flipped" lactate dehydrogenase isoenzyme pattern in serum from children with acute leukemia. PMID- 1914195 TI - Plasma renin activity and plasma prorenin assays. AB - Sensitivity and accuracy are essential features of an assay of plasma renin activity (PRA) because the normal concentration of PRA is only 1 pmol/L, and subnormal concentrations have diagnostic relevance. Conditions for blood collection need to be standardized but the conditions are not difficult for outpatients. For routine diagnostic purposes blood should be collected from ambulatory (ideally, untreated) patients on moderate sodium intake. To avoid irreversible cryoactivation of plasma prorenin (which is present in 10-fold greater concentrations than renin), samples should be processed at room temperature and stored completely frozen. Cryoactivation occurs when plasma is liquid at temperatures less than 6 degrees C. PRA is commonly measured with an enzyme kinetic assay in which angiotensin I (Ang I) is formed by the reaction of plasma renin with endogenous renin substrate (angiotensinogen). The Ang I so formed is measured by RIA; results are expressed as an hourly rate (micrograms/L formed per hour). This method, which is provided by most commercial kits, has the potential for unlimited sensitivity because the step for Ang I generation can be prolonged as long as necessary, so that enough Ang I forms to be measured accurately. Unfortunately, that sensitivity is not always exploited. Dilution of plasma during pH adjustment should be kept to a minimum. The Ang I generation step should last at least 3 h. The step should last 18 h for samples with PRA less than 1.0 micrograms/L per hour, to eliminate the errors inherent in the measurement and subtraction of immunoreactive Ang I in the untreated plasma (blank subtraction). These changes actually simplify PRA measurements because they eliminate the need for ice in the clinic and reduce by almost half the number of samples to be assayed by RIA. I also describe the method for measurement of plasma prorenin, which may be an important marker for patients with diabetes mellitus who subsequently develop vascular complications. PMID- 1914196 TI - Abnormal sodium metabolism and plasma renin activity (renal renin secretion) and the vasoconstriction volume hypothesis: implications for pathogenesis and treatment of hypertension and its vascular consequences (heart attack, stroke). AB - Arterial hypertension is sustained by either of two long-term mechanisms of arteriolar vasoconstriction or by an inappropriate reaction between them. One mechanism is renin-mediated, the other is related to antecedent renal sodium retention. The plasma renin value directly reflects the presence and degree of renin-mediated vasoconstriction, and, inversely, defines the predominance of sodium-related vasoconstriction. A hypotensive response, or lack of it, to angiotensin-converting enzyme inhibitor is similarly informative. Because the normal kidney exposed to high arterial pressure and normal salt intake will reduce its renin secretion to near zero, any renin secretion in a hypertensive setting can be considered abnormal. Typically, high-renin hypertensive patients are more vasoconstricted than low-renin patients with similar blood pressures. The intense vasoconstriction leads to relative hypovolemia, hemoconcentration, hyperviscosity, postural hypotension, and in severe forms even to acrocyanosis, all of which are dramatically reversed with anti-renin therapy. Conversely, low renin equally hypertensive patients have relatively more sodium volume and are less vasoconstricted; they are generally responsive to natriuretic drugs (e.g., diuretics or calcium antagonists) and appear relatively protected from vascular sequelae such as stroke and heart attack. These observations provide a new means for evaluating prognosis and a basis for mechanistically differentiating and treating hypertensive patients, allowing increasingly simpler and more-specific long-term therapies. PMID- 1914198 TI - The role of laboratory testing in the diagnosis of renovascular hypertension. AB - The diagnosis of renovascular hypertension depends heavily on laboratory tests. There is no universally applicable screening test, and it should be actively sought only in patients with clinical clues suggested by the history, physical examination, and routine laboratory testing. Hyperreninemia is a characteristic finding, and acute blockade of the renin system forms the basis of diagnostic tests such as the oral captopril test and captopril renography. Other abnormal laboratory findings include hypokalemia, proteinuria, and azotemia exacerbated by angiotensin-converting enzyme inhibitors. PMID- 1914197 TI - Role of vasopressin in clinical hypertension and congestive cardiac failure: interaction with the sympathetic nervous system. AB - The pressor action of vasopressin (AVP) in humans was investigated with the specific anti-vasopressor V1 antagonist d(CH2)5-O(Me)-Tyr-AVP. A single 0.5-mg intravenous bolus of this agent inhibited the pressor effect of AVP by about 80%. Normally hydrated humans had no blood pressure response to this dose, but this agent did prevent the blood pressure rise in response to exogenous AVP given in doses up to 200 milli-units/kg. Patients with severe hypertension, especially that associated with end-stage renal disease, tended to respond with moderate increases in blood pressure and plasma AVP after sodium overload and had a modest blood pressure fall (10-20 mmHg) in response to a single intravenous bolus of the AVP antagonist. Patients with an impaired sympathetic nervous system had increased sensitivity to the pressor action of AVP, in keeping with knowledge derived from experimental studies. These data suggest an interaction between AVP and alpha-adrenergic function, whereby the latter tends to attenuate the pressor action of AVP although it facilitates the release of AVP in response to various stimuli. In patients with congestive heart failure, the direct pressor action of AVP appears to contribute to increased systemic vascular resistance in about 30% of cases, i.e., those with plasma AVP concentrations well above the normal range. In these subjects, circulating AVP concentrations correlated with a decrease in vascular resistance in response to the V1 antagonist. PMID- 1914199 TI - Diabetic nephropathy: a disease causing and complicated by hypertension. AB - In examining the pathophysiology underlying the development of hypertension in diabetes mellitus, it is important to draw clear distinctions between Type I and Type II diabetes. In patients with Type I diabetes, with a peak onset of disease early in the second decade of life, hypertension clearly represents the sequelae to the development of substantial renal lesions, especially in the glomerulus. Thus the prevalence of hypertension in those patients without substantial glomerular lesions approximates the incidence of hypertension in the general population (approximately 4%). In patients with Type II diabetes mellitus and onset generally later in adult life, an increase in blood pressure can often be demonstrated early after or even before diagnosis of the disease (most readily demonstrated in the Pima Indians). Furthermore, clear familial tendencies towards the development of nephropathic complications of diabetes can be shown. In patients with Type I disease, the fall in glomerular filtration rate parallels the fall in glomerular capillary surface available for filtration. This reduction in the peripheral glomerular capillary surface correlates well with the expansion of the mesangium, strongly implicating the mesangial expansion in the demise in renal function. For both Type I and Type II diabetes mellitus, the increase in albuminuria may reflect an opening of large pores in the glomerular basement membrane, thereby allowing serum proteins to cross into the filtration space. PMID- 1914200 TI - Steroid characteristics of mineralocorticoid adrenocortical hypertension. AB - Adrenocortical causes of hypertension are established by examining the mineralocorticoid hormones produced in the zona glomerulosa and zona fasciculata. In the zona glomerulosa, aldosterone excess leads to hypertension, hypokalemia, and suppressed plasma renin activity, with increased concentrations of urinary aldosterone (either as the 18-glucuronide or free aldosterone) as an index of its production. Identifying a tumor by computed tomography scan verifies the diagnosis of a correctable lesion. If no tumor is found, several maneuvers are used to identify primary adrenal hyperplasia, a disorder with autonomous aldosterone production, for which reduction of adrenal mass is curative. The zona fasciculata has two major pathways: the 17-deoxy pathway, where deoxycorticosterone (DOC) and corticosterone are the significant steroids, and the 17-hydroxy pathway, which leads to cortisol production. Tumors of the 17 deoxy pathway, DOC-producing adenomas, have increased concentrations of DOC and its precursor steroids, normal concentrations of cortisol, and suppression of aldosterone production secondary to suppression of the renin system. Two enzymatic defects in the zona fasciculata, 11 beta- and 17 alpha-hydroxylase deficiency, can be first readily identified by the virilization in the former, hypogonadal features in the latter. Steroid patterns are diagnostic. DOC is produced in excess in both deficiencies and is the cause of the hypertension. Deficient or impaired 11 beta-hydroxy steroid dehydrogenase in the apparent mineralocorticoid excess syndrome or after licorice ingestion retards the conversion of cortisol to inactive cortisone in the kidney, leading to mineralocorticoid hypertension; this leads to suppression of the renin system and subsequently of aldosterone. PMID- 1914201 TI - Adreno-medullary hypertension: a review of syndromes, pathophysiology, diagnosis, and treatment. AB - Hypertension may be attributable to various disorders involving the central or peripheral adrenergic (catecholamine) pathways. Pheochromocytoma is the best known of these disorders, but many syndromes mimic the clinical features of this tumor. In adreno-medullary hypertension, cardiovascular tissues are stimulated by activation of alpha or beta adrenergic receptors, or both. Specific diagnosis of adreno-medullary hypertension depends on careful clinical assessment and selection of sensitive and specific biochemical tests for measuring the catecholamines and their principal metabolites in urine or plasma. If such tests indicate the presence of a chromaffin cell neoplasm, accurate localization (imaging) is provided by computed axial tomography (CAT) or magnetic resonance imaging (MRI). Adreno-medullary hypertension is effectively controlled, pharmacologically, by alpha and beta receptor antagonists, which may be given intravenously for emergencies. Excess catecholamine synthesis by pheochromocytomas can be reduced by methyltyrosine. Surgical cure of pheochromocytomas can be expected in most instances, but long-term surveillance for recurrent tumors, some of which may be malignant, is needed. Chemotherapy can reduce the tumor bulk of a malignant pheochromocytoma. Recent use of molecular biology techniques may be helpful in early detection of malignant transformation. PMID- 1914202 TI - Advances in catecholamine and metabolite measurements for diagnosis of pheochromocytoma. AB - Assessment of catecholamine production and excretion is important in the laboratory detection of pheochromocytoma, a rare but curable cause of hypertension. Advances in catecholamine and metabolite methodologies have enhanced the diagnostic acumen by increasing analytical sensitivity and eliminating many of the interferences observed with earlier methods. Estimation of urinary catecholamines metanephrine and vanillylmandelic acid is routinely used in the biochemical detection of pheochromocytoma and in monitoring the completeness of tumor excision as well as the possibility of recurrence. Traditional spectrophotometric and fluorometric methods for urinary catecholamines and their metabolites are being replaced by highly sensitive and selective chromatographic methods. The ability to quantify individual catecholamines and metanephrines by high-performance liquid chromatography is of particular value for detecting familial forms of the tumor that may secrete epinephrine. Plasma norepinephrine and epinephrine measurements are of additional diagnostic value in determining recent catecholamine release and response to clonidine suppression. For either urine or plasma measurements, appropriate patient preparation, sample collection, and method validation along with an understanding of the variable pattern of catecholamine secretion and metabolism in pheochromocytoma are essential. Advances in laboratory methodology and reference intervals for catecholamines for clinical interpretation are reviewed. PMID- 1914203 TI - Clinical evaluation and differential diagnosis of the individual hypertensive patient. AB - This paper attempts to define the theory and practice of a modern approach to the initial workup of the patient with hypertension. The process includes a complete general medical evaluation along with special measures to enable the fullest characterization and clinical differentiation of the disease. The initial workup aims to (a) establish that the hypertension is sustained and should be treated; (b) identify all definable and curable causes for the hypertension; (c) identify the presence and degree of attendant risk factors such as smoking, alcohol use, obesity, diabetes, and abnormal lipid metabolism; (d) characterize the hypertension in terms of its pathophysiology; and (e) assess the presence and degree of target organ damage to the heart, brain, and kidneys. Because all diastolic hypertension is due to arteriolar vasoconstriction, a fundamental strategy of this process is to distinguish between renin-mediated and sodium related vasoconstrictive forces and to evaluate which is preponderant. The chief instruments of this strategy are the renin-sodium profile and the response of plasma renin activity and blood pressure to specific antirenin system drugs. The captopril test, an important protocol in making this distinction, is primarily a powerful screening tool for confirming the possible presence or absence of curable renovascular disease or curable primary aldosteronism. That renin profiling cannot accurately discriminate between the contributions of either the renin or sodium-volume factors in that large fraction of medium-renin patients is not a viable reason for not performing the test. The test has its greatest strength for identifying sizable numbers of otherwise unrecognizable patients with very high or very low renin concentrations who might have curable disorders and who likely reflect different pathophysiologic vasoconstrictive mechanisms for which entirely different drug therapies are appropriate. However, the baseline renin test is also useful for assessing prognosis and the likelihood of a heart attack and it is valuable for deciding whether to use an anti-renin system drug (for medium and high renin concentrations) as opposed to natriuretic agents (low renin patients) such as a diuretic or calcium antagonists as the primary step. In our present state of knowledge, the basic diagnostic biochemical workup includes the renin-sodium profile and the 24-h urinary sodium, potassium, and microalbumin excretion rates. This package is further enriched by baseline electrocardiography and echocardiography and the evaluation of glucose and lipid patterns.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1914204 TI - Applications of ambulatory blood pressure monitoring in clinical practice. AB - Traditionally, blood pressure has been measured by the sphygmomanometer in the medical office. There is growing evidence, however, that office blood pressures may not be typical of values throughout the day. Between 20% and 30% of patients diagnosed with hypertension in the office actually are normotensive at other times. Ambulatory blood pressure monitoring with small, portable devices that automatically measure blood pressure every few minutes throughout the day appears to be an appropriate tool when "white-coat" hypertension is suspected--i.e., for individuals whose hypertension in the physician's office is not associated with other physical or historical evidence for cardiovascular disease or with other risk factors. Used prudently, ambulatory monitoring is a cost-effective technique that potentially can prevent unnecessary treatment of patients. Moreover, whole day measurements may correlate more closely than office measurements may correlate more closely than office measurements do with findings of cardiovascular disease. This new approach also has highlighted the circadian pattern of blood pressure, especially the sharp early to mid-morning increase that coincides with an increased tendency to major cardiovascular events. This has focused attention on directing antihypertensive therapy towards the morning hours. Ambulatory monitoring is now used routinely in studies of antihypertensive drugs. This technique has no placebo effect and takes fewer patients to assess drug efficacy than do conventional methods. PMID- 1914205 TI - Heterogeneity among hypertensive subjects: a tool for clinical decision-making. AB - Current antihypertensive treatment strategy tends to approach all patients similarly, with decision to treat, the goal of treatment, and medication use based largely on blood pressure measurement. Clearly, it would make far more sense if a management strategy could be developed that was not solely dependent on measurement of blood pressure, but rather reflected a clearer understanding of individual likelihood of adverse outcome, the nature of blood pressure control, and the importance of associated clinical and biological characteristics. New tools make it possible to accurately assess the status of the heart, kidney, and blood vessels, both as a guide to the need for therapy and as a measure of treatment progress when the treatment is used. New understanding of the vasoconstrictor and volume contributions to blood pressure control coupled with a rich armamentarium of therapeutic agents make it possible to tailor therapy more appropriately. Finally, growing awareness of the contribution of concomitant risk factors has made it clear that overall success depends on attention to the whole patient. PMID- 1914206 TI - Evolution of the indications for cesarean section. Results of a retrospective study. AB - We have analysed in retrospect the incidence of cesarean section during the years 1977-1989 in the 1st Obstetric and Gynecologic Clinic of the University of Bologna, and the development over time of the principal indications. The average incidence (17.1%) of cesarean section increased progressively from 9% in 1977 to 28% in 1989 with a peak at the beginning of the '80s (the period during which cardiotocographic monitoring became routinely used). With regard to the indications from 1977 up to date cesarean sections carried out on account of fetal distress increased almost five-fold. The increase in cesarean sections carried out on account of maternal disease, breech presentation and previous cesarean section was less important, while those performed for dystocia resulted markedly reduced. PMID- 1914207 TI - Dysmenorrhoea and sports activities in adolescents. AB - Primary or essential dysmenorrhoea is a painful syndrome which precedes by a few hours or accompanies the menstrual flow, present above all in adolescents. The aim of the present work is to evaluate the incidence of dysmenorrhoea in adolescents who practice sports. We examined two groups of athletes who practised sport in their adolescent period: 1) first population of athletes (483 subjects): women who had begun their activity before menarche (Group A: 261 subjects) and athletes who had started some years after the menarche (222 subjects); and in this latter group before (Group B1) and after (Group B2) the beginning of sports activity. 2) Second population (281 subjects) comprising: Group C (169 adolescents) comprised women who took part in sport only now and then; Group D (112 women) whose activity was of an athletic type. Comparing the percentage of dysmenorrhoea it emerges: 1) that dysmenorrhoea is present in a lower percentage in subjects in Group A (68.19%) in respect to women in Group B; 2) that in a considerable number of girls in Group B it was observed that there was a regression or an improvement in the pain symptomatology after the beginning in athletic activity; 3) dysmenorrhoea was much less in the more intense the sports activity (Groups C and D). From these data it can therefore be seen that athletic activity of almost any type or level has a positive influence on the dysmenorrhoea symptom, while it does not produce the same effect on other characteristics of the cycle, indeed, in some cases they were worsened. PMID- 1914208 TI - The residual ovary after hysterectomy. AB - Of 118 cases of patient who had undergone abdominal hysterectomy with the preservation of one or both the ovaries, only 73 patients (62%) attended for review. Eleven had had cysts of the residual ovary. The occurrence of an asymptomatic pathology in three cases suggest that patients, for whom preservation of an ovary was considered preferable, should undergo a periodic clinical and ultrasonographic review. PMID- 1914209 TI - Angular pregnancy. Clinical management. AB - A case of angular pregnancy was diagnosed by ultrasound examination after curettage of abortion hemorrhage. The rarity and clinical management of this condition are discussed, as well as the importance of ultrasound investigation for early diagnosis. PMID- 1914210 TI - Ovarian leiomyoma. Case report. AB - We describe a case of primary ovarian leiomyoma in a 16 year old patient; both ovaries were affected. Since at intervention normal tissue was found, the left ovary was preserved and a 30-months follow-up was carried out. Tumour markers (CA 125; alpha-fetoprotein; CEA and beta-HCG) were tested. Such a case has not previously been reported. Etiopathogenesis is also discussed. PMID- 1914211 TI - Vaginosonography in primary prevention of endometrial oncological pathology. AB - In 38 patients observed for postmenopausal bleeding endometrial thickness measured by vaginosonography before diagnostic curettage was compared with histological results. In 30 patients with endometrial thickness below 4 mm only inactive endometrium was found, whereas in 8 patients with endometrial thickness above 4 mm different pathologies were present. The role of vaginosonography in primary prevention of endometrial oncology is discussed. PMID- 1914212 TI - One case of "prune belly" syndrome: prenatal and prognostic valuation. AB - A case of "Prune Belly" syndrome, its sonographic diagnosis, from the 15th week and its monitoring by sonography and biochemical exams of fetal urine for study of renal function is described. The good relation between prenatal prognosis and neonatal renal function is verified after birth. PMID- 1914213 TI - Non-puerperal vulval haematoma. AB - A case of non-puerperal vulval haematoma has been presented. The aetiology and surgical management plan of this uncommon condition has been discussed. PMID- 1914214 TI - Reproductive capacity and outcome of pregnancy after metroplasty following the technique of Bret-Palmer partially modified in the pathological symmetric malformations of mullerian ducts. AB - During the period 1977-90, metroplasty for infertility and unexplained sterility was performed respectively in 19 and 6 cases of symmetric uterine malformations. The Bret-Palmer technique was used in 6 cases for partial septate uterus, while the same modified technique was performed in 11 cases of complete bicornuate uterus and in 8 cases of partial bicornuate uterus. No operative and postoperative complications were noted. With the modified Bret-Palmer operation there was the reconstruction of a single, large and regular uterine cavity. Of the 17 cases with adequate follow-up pregnancy occurred in 14 cases within 24 months of the operation; in 4 patients the outcome of pregnancy is not known. Of the remaining cases the pregnancy ended in spontaneous abortion in 2 patients, in 6 cases with live term infants and in 2 cases with live preterm infants. Caesarean section was performed electively in 3 cases and acutely in 3 cases. A vaginal delivery occurred in 2 cases. Benefits of the Bret-Palmer modified technique are discussed. PMID- 1914215 TI - Abnormal cervical cytologic, colposcopic and histologic findings in exposed DES young Israeli Jewish women. AB - A consistently higher rate of abnormal cervical cytology, colposcopic and histologic findings in 89 DES exposed Israeli Jewish women was found as compared to 318 women in a control group. This trend however reached statistical significance for abnormal colposcopic and histologic findings only in the 25-34 age group. The higher rate of abnormal findings can be attributed to DES exposure and not to an excess of other risk factors in the study group. Routine cytologic and colposcopic examination is recommended for DES exposed Israeli Jewish women who are otherwise at low risk for development of cervical neoplasia. PMID- 1914216 TI - Ultrasonic and postnatal findings in left visceral isomerism. AB - Sonographic and postmortem findings of left visceral isomerism associated with polysplenia are reviewed. Particular stress is given to pathologic data, which could prospectively suggest some specific ultrasonic features in order to characterize this complex syndrome. PMID- 1914218 TI - The influence of anemia on respiratory gases and acid base parameters of the fetus. AB - Fetal blood samples were collected by cordocentesis from 82 pregnant women; 12 of whom had severe forms of Rh isoimmunization, while 70 comprised the control group. The mean hematocrit value in the group under investigation was 15.72 +/- 3.62% and indication of severe anemia. The pH value in this group was 7.31 +/- 0.06; pCO2 partial pressure 6.36 +/- 0.64; O2-2.65 +/- 0.89 kPa; bicarbonate 23.84 +/- 3.02 mMol/l: base excess was -2.72 +/- 2.66 mMol/l and saturation 28.66 +/- 15.56%. In the control group the following values were established: pH -7.386 +/- 0.05; partial pressure pCO2-4.980 +/- 0.31 kPa; O2--4.960 +/- 0.90 kPa; bicarbonate 21.560 +/- 0.27 mMol/l; base excess -2.30 +/- 0.90 mMol/l and saturation 67.23 +/- 11.60%. The pH, partial pressure O2 and saturation values were significantly lower, while partial pressure CO2 was significantly higher in the investigated group than in the control group. Bicarbonates and base excess do not change significantly in the presence of anemia. Fetal blood sampling carried out by means of cordocentesis is the most reliable method for assessment of the degree of fetal anemia. The values of acid base parameters and of blood gases are an indication of either respiratory, respiratory-metabolic or metabolic acidosis. The possibilities of prenatal diagnostics, undoubtedly, contribute to a significant reduction of perinatal mortality. PMID- 1914217 TI - Respiratory gases and acid base parameter of the fetus during the second and third trimester. AB - Respiratory gases and acid base parameters were determined in the samples of fetal blood collected by cordocentesis from 70 patients with normal course of pregnancy, between 18th and 38th gestational week. The mean pH value was 7.386 +/ 0.05; partial pCO2 pressure -4.819 +/- 1.464 kPa; O2-5.712 +/- 1.24 kPa; bicarbonate 21.528 +/- 0.494 mMol/l; base excess -2.284 +/- 0.647 mMol/l and saturation 74.86 +/- 13%. Statistically significant negative correlation between gestational age and pH (r = 0.841, p less than 0.01) and partial O2 pressure (r = -0.961, p less than 0.01) was revealed. Partial CO2 pressure correlated significantly with gestational age (r = 0.923, p less than 0.01). The values of bicarbonate and base excess do not change significantly during gestation. Our own standards of examined parameters were formed. PMID- 1914219 TI - Alkaline phosphatases in biology and medicine. PMID- 1914220 TI - Interactions of the salivary and gastrointestinal systems. II. Effects of salivary gland dysfunction on the gastrointestinal tract. AB - Salivary gland dysfunction is uniformly detrimental to the oral cavity. Its effects on the GI tract have begun to be explored. Dry mouth is a common complaint among older adults, probably due to systemic disease and its therapy rather than the aging process per se. Evaluation of complaints of dry mouth should include medical history, sialometry and physical examination. Numerous medications can elicit drug-induced xerostomia. Patients who have received radiation therapy to the head and neck region often have permanent radiation induced xerostomia, which has been linked to esophagitis. SS is an autoimmune systemic exocrinopathy resulting in irreversible salivary gland dysfunction. SS has numerous GI manifestations, including dysphagia, temporal defects of deglutition, esophageal dysmotility, gastritis, pancreatitis and liver disease. Management of salivary hypofunction is directed toward preserving the dentition and improving patient comfort. Drug-induced xerostomia is often correctable by altering the therapeutic modality. PMID- 1914221 TI - Sphincter of Oddi motility and its disorders. PMID- 1914222 TI - The role of ciclosporin therapy in Crohn's disease. A review. PMID- 1914223 TI - Qualitative difference of anti-DNA antibody-producing cell precursors in the pre immune B cell repertoire between normal and lupus-prone mice. AB - The precursor frequency for anti-DNA antibody-producing cells in the pre-immune B cell repertoire was investigated in young female BALB/c and NZW mice, and in young and aged female NZB x NZWF1 (B/WF1) mice. Spleen cells from these mice were diluted serially and stimulated polyclonally in vitro with lipopolysaccharide (LPS) and IL-4 to induce both IgM and IgG1 production. The results demonstrated that there existed virtually no difference in precursor frequency for IgM anti DNA antibody-producing cells between normal and lupus mice, confirming previous observations made by other investigators. In contrast, the number of precursors for IgG1 anti-DNA antibody-producing cells was much higher in young and old B/WF1 mice than in normal mice. These results suggest that the high frequency of precursors for IgG1 anti-DNA antibody-producing cells in the pre-immune B cell repertoire of B/WF1 mice is a crucial factor for the pathogenesis of systemic lupus erythematosus. PMID- 1914224 TI - Spontaneous development of autoimmune uveoretinitis in nude mice following reconstitution with embryonic rat thymus. AB - This paper describes the spontaneous occurrence of an autoimmune uveoretinitis in nude (nu/nu) mice reconstituted when 4 weeks old by the grafting of rat embryonic thymus. The uveoretinitis was characterized histologically by progressive loss of the photoreceptor layer, observed in 4.0, 17.6, 42.9% and 71.4% of such mice at 3, 5, 7 and 12 months of age, respectively. Mice with uveoretinitis were shown to have serum IgG antibody reactive by indirect immunofluorescence with retinal photoreceptors, and with interphotoreceptor retinoid-binding protein (IRBP), but not retinal S-antigen, by immunoblotting and ELISA. A uveoretinitis could be adoptively transferred to syngeneic ungrafted nude mice by splenic CD4+ T cells from diseased animals. This is the first experimental model of a (T cell mediated) autoimmune uveoretinitis which develops spontaneously and which is not dependent upon deliberate sensitization with retinal antigens and adjuvants. PMID- 1914225 TI - Increased expression of class II major histocompatibility complex molecules on B cells in rats susceptible or resistant to HgCl2-induced autoimmunity. AB - Administration of HgCl2 to the susceptible Brown-Norway (BN) rats induces an autoimmune disease characterized by a T-dependent polyclonal activation of B cells responsible for a dramatic increase in serum IgE concentration. The resistant Lewis (LEW) rats injected with HgCl2 do not exhibit such autoimmune manifestations. We show here that, upon HgCl2 injections, major histocompatibility complex (MHC) class II molecule expression is increased very early in lymph nodes and spleen B cells from both strains. So far, it is the earliest marker (day 3) of the effect of HgCl2 on the immune system. In both strains this enhancement is transient, but regulatory mechanisms are much more efficient in the resistant LEW strain than in the susceptible BN strain. In addition, we observed that MHC class II molecule expression on B cells differs according to the organ and the rat strain tested. All these findings are discussed in an attempt to underline the role of MHC class II molecule expression in the occurrence of mercury-induced autoimmunity. PMID- 1914226 TI - Serum soluble CD4 and CD8 levels in Kawasaki disease. AB - The levels of soluble CD4 (sCD4) and sCD8 in serum correlate with the T cell subset activation and may be important in monitoring and characterizing disease processes during immunological diseases. We compared acute Kawasaki disease (KD) with anaphylactoid purpura (AP) and acute febrile viral infections, such as measles and infectious mononucleosis (IM), in terms of serum sCD4 and sCD8 levels. The levels of serum sCD4 and sCD8 were measured by a sandwich enzyme immunoassay. In addition, peripheral blood mononuclear cell subsets were analysed by single and two-colour flow-cytometric analyses in KD and IM patients. The levels of serum sCD4 and sCD8 were significantly elevated in patients during acute stages of KD, measles and IM, but not AP. Peripheral blood CD4+, CD8+ and also HLA-DR+ T cells count did not increase during the acute stage of KD; however, peripheral blood CD8+ and HLA-DR+ T cell counts were increased during the acute stage of IM. Our results suggest that there is a low level of activation of peripheral blood T cells during acute KD, or that infiltrated T cells in some local tissues of KD patients contribute to the elevated levels of serum sCD4 and sCD8. PMID- 1914227 TI - Urinary IL-6: a marker for mesangial proliferative glomerulonephritis? AB - A prospective study of plasma and urinary interleukin-6 (IL-6) levels was performed in 54 patients undergoing renal biopsy to determine whether detectable urinary IL-6 was a reliable marker for mesangial proliferation. Interleukin-6 was found in both the urine and plasma of seven patients, the urine alone of 15 patients, and the plasma alone of two patients. Interleukin-6 was not detected in the urine or the plasma of the remaining 30 patients, the urine of 10 healthy controls or the urine of 10 patients with rheumatoid arthritis with raised plasma IL-6. Interleukin-6 was found in the urine of only one out of an additional seven patients with lupus nephritis. Urinary IL-6 was associated with a variety of renal abnormalities and was not restricted to those with mesangial hypercellularity. Furthermore, many patients with mesangial hypercellularity did not have detectable urinary IL-6. There was no correlation between urinary IL-6 and plasma IL-6, urinary albumin excretion or urinary creatinine. These results suggest that IL-6 detected in the urine is a marker of renal IL-6 production, but not specifically of mesangial hypercellularity. The patients with IL-6 in the urine had a mean serum creatinine significantly higher than those without IL-6. It is not possible to distinguish at present whether IL-6 contributes to renal dysfunction or whether it reflects renal damage. PMID- 1914228 TI - Fibronectin and basement membrane components in renal amyloid deposits in patients with primary and secondary amyloidosis. AB - Kidney biopsies from one patient with primary (AL) and three with secondary (AA) amyloidosis were used for an ultrastructural study of the collocalization of basement membrane proteins and the extracellular matrix protein fibronectin within amyloid deposits. Antibodies against amyloid P component, laminin, and heparan sulphate proteoglycan core protein all reacted with the basement membranes and the amyloid depositions in AA and AL amyloidosis. Monoclonal and polyclonal antibodies against collagen type IV reacted only with the basement membranes. Anti-fibronectin reaction was found in association with the basement membranes in all four cases, while labelling of amyloid depositions was found only in one of the AA amyloid cases and in the AL amyloid depositions. It is concluded that basement membrane components may be of importance for the formation of amyloid fibrils. PMID- 1914229 TI - Differentiation between vascular permeability factor and IL-2 in lymphocyte supernatants from patients with minimal-change nephrotic syndrome. AB - Immunotherapy of cancers with recombinant IL-2 induces a vascular leak syndrome which is mainly due to an increase in vascular permeability. A lymphokine, the vascular permeability factor (VPF), which increases vascular permeability, has been characterized in minimal-change nephrotic syndrome (MCNS) and appeared very similar to IL-2. Here we have undertaken a further characterization of VPF in order to determine how closely related this factor was to human IL-2. Both the IL 2 bioassay and Western blot analysis of the MCNS lymphocyte concentrated supernatants with high VPF activity revealed the presence of low quantities of IL 2. Preparative isoelectrofocusing (IEF) of concentrated supernatants resolved each lymphokine in a separate peak, with apparent pIs of 5.2 for VPF and 7.5-10.1 for IL-2. Since a sensitive IL-2 ELISA failed to exhibit any significant antigenic presence of IL-2 in the IEF fractions with the highest VPF activity, we conclude that VPF activity of the concentrated supernatants is not related to IL 2 nor to a biologically inactive form of IL-2. When concentrated supernatants were subjected to preparative SDS-PAGE, VPF activity was recovered within low mol. wt material (1-12 kD). Immunoadsorption experiments gave definite proof since the complete removal of IL-2 from concentrated supernatants did not affect the VPF activity. Although high amounts of IL-2 increased vascular permeability, our experiments clearly demonstrate that VPF is a lymphokine distinct from IL-2. PMID- 1914230 TI - Alveolar macrophages from patients with bronchogenic carcinoma and sarcoidosis similarly express monocyte antigens. AB - It has been shown that bronchoalveolar lavages (BALs) from patients with sarcoidosis and other interstitial lung diseases contain abnormally increased numbers of alveolar macrophages (AM) expressing antigens found on monocytes. The aim of this study was to compare the phenotype of AM from patients with sarcoidosis with those from patients with non-interstitial lung disease, namely carcinoma. Using a panel of monoclonal antibodies against cells of the mononuclear phagocytic series and immunohistochemical staining, we have compared the expression of antigens on AM recovered at BAL and peripheral blood monocytes from patients with sarcoidosis, with similar cell preparations from bronchogenic carcinoma patients and normal volunteers. We have shown that CD14, CR1 (CD35) and CR3 (CD11b, CD18) are expressed on the majority of monocytes from all subjects, but on only a minority of normal AM. In both patients with sarcoidosis and patients with bronchogenic carcinoma increased proportions of AM expressed these monocyte-associated antigens. Since BALs from the carcinoma patients were derived from lung lobes which were radiologically free of tumour, the accumulation of AM expressing monocytic antigens is not a local response to the tumour. We conclude that infiltration of the lung with monocytes is a more general response to lung disease than has hitherto been reported. PMID- 1914232 TI - Human cerebral malaria: characterization of malarial antibodies in cerebrospinal fluid. AB - Anti-malarial antibodies were quantified in cerebrospinal fluid (CSF) of 17 cases of cerebral malaria, 16 presumptive cases (no demonstrable parasitaemia in peripheral blood but responding to i.v. quinine therapy) of cerebral malaria, and 15 controls. A schizont-enriched Plasmodium knowlesi antigen was used in an ELISA. Anti-malarial antibodies of IgA and IgM isotypes were not detectable in most of the CSF samples analysed, although serum antibody titres were high. However, 88% of CSF from cerebral malaria and 56% of presumptive cerebral malaria cases had significant levels of IgG anti-malarial antibodies in comparison to control CSF. The antibody levels did not correlate with the severity of coma but correlated well with the duration of coma. The CSF malarial antibody titres were independent of degree of parasitaemia. The possible role of CSF anti-malarial antibodies in cerebral malaria in the light of recent demonstrations of intrathecal synthesis of immunoglobulins and deposition of immune complex in cerebral tissues is discussed. PMID- 1914231 TI - Eosinophils adhere to and stimulate replication of lung fibroblasts 'in vitro'. AB - Eosinophils have been implicated in several disorders associated with the development of fibrosis. This led us to investigate the interactions between eosinophils and fibroblasts in vitro. Adhesion between purified guinea pig peritoneal eosinophils and monolayers of human fetal lung fibroblasts was assessed using the rose bengal dye staining assay. Fibroblast replication was assessed using a colorimetric assay based upon the uptake and subsequent release of methylene blue. Addition of phorbol myristate acetate induced a rapid, time dependent increase in eosinophil adhesion (127% and 328% over basal adhesion after 10 and 30 min, respectively). Phorbol myristate acetate-induced adhesion was inhibited by the peptides RGDS and GRGDS (48% and 42%, respectively using 1 mM peptide) and by nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway of arachidonic acid metabolism (46% inhibition at 15 microM). In addition, 24 h culture of fibroblast monolayers with interleukin 1 alpha (IL-1 alpha) or tumour necrosis factor alpha (TNF alpha) resulted in enhanced adhesion (10 U/ml IL-1 alpha stimulated adhesion by 55% of control, 500 U/ml TNF alpha by 75% of control). Conditioned media from cultured eosinophils stimulated fibroblast replication in a time-dependent fashion with maximal stimulation at 3 h. In contrast, media from guinea pig peritoneal macrophages in culture did not show such an effect. This study indicates that eosinophils are capable of both adhering to and releasing mitogens for fibroblasts in vitro. These observations suggest that eosinophils have the capacity to play a role in the development of fibrosis in disorders where they have been shown to be present. PMID- 1914233 TI - Heat shock proteins: friend and foe? PMID- 1914234 TI - Lymphocyte proliferative responses to chlamydial antigens in human chlamydial eye infections. AB - In order to study the relationship between cell-mediated immune responses to Chlamydia trachomatis and the pathogenesis of human chlamydial eye disease, we have measured the peripheral blood lymphocyte proliferative responses to whole chlamydial elementary bodies in 40 subjects with oculogenital chlamydial infection of varying severity, 13 subjects with genital chlamydial infections and 12 healthy seronegative controls. The mean stimulation index was significantly higher in those with oculogenital infections than in controls. There was a strong correlation between the response to C. trachomatis serotypes B and L1. We studied the relationship between proliferative responses and four clinical parameters: follicular conjunctivitis, papillary hypertrophy, corneal pannus and epithelial punctate keratitis, but were unable to show a significant association with any of these. Nor was there any association between proliferative response and serum antibody titre to C. trachomatis (pooled serotypes D-K), duration of disease or quantitative isolation of chlamydia from the conjunctiva. The depletion of CD8+ cells had no consistent effect on proliferative responses to serotype L1 in 13 subjects. PMID- 1914235 TI - IgM rheumatoid factor in congenital syphilis: associations with clinical and laboratory findings. AB - IgM rheumatoid factor (RF), measured by means of an ELISA, was detected in 92% of infants with congenital syphilis. Elevated levels were found to correlate with liver and renal involvement as well as the extent of the disease (P less than 0.05). In addition, levels of circulating immune complexes were closely related to the RF concentration (P less than 0.001). Following treatment of the infants both RF levels and VDRL titres declined at a similar rate (P less than 0.001). These findings indicated a close relationship between the disease process and IgM RF levels. It is postulated that IgM RF may add to immune complex deposition and exacerbate tissue damage in congenital syphilis. PMID- 1914236 TI - Autoantibody stimulation of the human thyrotropin receptor: regulation of adenylate cyclase activity, thyroglobulin and thyroid peroxidase mRNA levels in primary cultures of Graves' thyroid tissue. AB - The effects of immunoglobulin preparations from hyperthyroid Graves' disease patients on primary cultures of thyroid cells have been studied at the mRNA level. Autoantibodies to the thyrotropin (TSH) receptor from these patients, which had been initially characterized by their ability to stimulate adenylate cyclase and inhibit the binding of radiolabelled TSH to thyroid membrane preparations, were studied for their effects on thyroglobulin and thyroid peroxidase mRNA levels. Incubation of thyroid cells with TSH receptor autoantibodies from different Graves' disease patients for 48 h led to time- and dose-dependent increases in the levels of thyroid peroxidase and thyroglobulin mRNA in primary cultures of thyrocytes. The incomplete correlation between G protein-linked adenylate cyclase activation and thyroid mRNA elevation indicates the possibility of the involvement of alternative second messenger pathways in the regulation of thyroid cell function and differentiation. PMID- 1914238 TI - Occurrence of lymphocytotoxins in multi-case rheumatoid arthritis families: relation to HLA. AB - The presence of lymphocytotoxic antibodies (LCA) and their association with HLA haplotypes has been studied in 27 multi-case rheumatoid arthritis (RA) families (13 multiplex and 14 simplex) in Northern India. Of the total 59 RA patients, 69.4% had cytotoxins in their sera as compared with 2.5% of healthy controls. No differences were observed in the frequency of LCA in relation to sex and rheumatoid factor. LCA against B cells were significantly more predominant than those against T cells. Twenty families studied for correlation of HLA with LCA showed greater intensity of reaction with DR4+ haplotypes, particularly in simplex families. Similarly, the frequency of LCA among patients and unaffected parents was greater in simplex compared with multiplex families. Haplotype sharing with the patient was increased in the relatives positive for cytotoxins in these families. An immunogenetic contribution made by the affected parent and a common environmental stimulus may be responsible for the increased production of LCA in multi-case families with RA. PMID- 1914237 TI - Identification of the major fibroblast growth factors released spontaneously in inflammatory arthritis as platelet derived growth factor and tumour necrosis factor-alpha. AB - Rheumatoid arthritis is characterized by chronic inflammation and proliferation of a number of important elements within the joint including the synovial fibroblasts. Elevated levels of a number of cytokines such as Il-1, IL-2, IL-6, interferon-gamma (IFN-gamma), transforming growth factor-beta and tumour necrosis factor-alpha (TNF-alpha) have been detected in the synovial fluid of patients with rheumatoid arthritis and other inflammatory arthritides. It seems likely that local release of such mediators may be responsible for the proliferation and overgrowth of connective tissue elements in these disorders. In order to ascertain whether there was evidence to suggest local production or release of fibroblast growth factors in the joint in inflammatory arthritis, and to determine their identity, cells were obtained from the synovial fluid of 15 patients with chronic inflammatory arthritides. All subjects' synovial fluid cells spontaneously released growth factor activity for fibroblasts. This was present in large amounts, being detectable in culture supernatants diluted to a titre of at least 1/625. By a series of depletion experiments using solid-phase bound antibodies to cytokines, it was possible to demonstrate that this activity was due to TNF-alpha and platelet-derived growth factor (PDGF). Thus, this study showed for the first time that functionally active PDGF was released from synovial fluid cells. Both PDGF and TNF-alpha appeared to contribute in approximately equal amounts to this fibroblast growth factor activity, and were synergistic in effect. Thus this study provides evidence for the local production and release of these two cytokines and suggests that together they are the dominant factors in fibroblast proliferation within the synovial cavity. PMID- 1914240 TI - On making multiple comparisons in clinical and experimental pharmacology and physiology. AB - 1. It is a central thesis of this review that in clinical and experimental pharmacology and physiology the goal of statistical analysis should be to minimize the risk of making any false-positive inferences from the results of an experiment (experimentwise Type I error). 2. It is common in clinical and experimental pharmacology and physiology for the effects of several treatments to be tested within a single experiment. Specific intercomparisons of these several effects, made in a pairwise or more complex fashion, inflates the risk of making false-positive inferences unless special statistical procedures are used. 3. A number of multiple comparison procedures is described and their ability to control experimentwise Type I error is evaluated critically. 4. When only a few (less than 5) of all possible pairwise or more complex comparisons are made between treatment groups, the Dunn-Sidak procedure provides maximum protection against excessive experimentwise Type I error and is very convenient to use. 5. When a control group is compared with all other treatment groups in a pairwise fashion, especially when the number of groups is large, the Dunnett procedure is more powerful than the Dunn-Sidak. 6. If investigators insist on making all possible pairwise comparisons among treatment groups, the Tukey-Kramer procedure provides maximum protection against false-positive inferences but inflates the Type II error rate. If it is especially important to avoid Type II error then the more complicated, stepwise procedures of the Ryan-Peritz-Welsch variety should be considered. PMID- 1914239 TI - Detection and occurrence of the 60- and 52-kD Ro (SS-A) antigens and of autoantibodies against these proteins. AB - The simultaneous detection of anti-La, anti-60-kD Ro and anti-52-kD Ro antibodies by immunoblotting is greatly improved by changing the crosslinking level in the gel to an acrylamide/bisacrylamide ratio of 19:1. Using this method for the analysis of a number of systemic lupus erythematosus (SLE) and Sjogren's syndrome patient sera it was observed that antibody to the 52-kD Ro protein without anti 60-kD Ro antibody was restricted to Sjogren's syndrome patients (9/26), whereas antibody to the 60-kD Ro protein without contaminating anti-52-kD Ro antibody was only found in SLE patients (8/38). Moreover, in Sjogren's syndrome patient sera anti-Ro antibody was found only in combination with anti-La antibody (20/26), whereas in SLE patient sera anti-Ro antibody could be found without detectable anti-La specificity (4/38). Double immunofluorescence microscopy revealed that the 52-kD Ro and the 60-kD Ro proteins co-localize in the cytoplasm as well as in the nucleus, whereas immunoprecipitation of [32P]-labelled HeLa cell extract with monospecific anti-52-kD Ro and anti-60-kD Ro sera showed that both proteins are associated with the Ro RNAs. These data suggest the presence of both the 52-kD and the 60-kD Ro proteins in the same ribonucleoprotein complexes. To study the evolutionary conservation of the 52-kD Ro, the 60-kD Ro and the La proteins, extracts of cell lines derived from various mammalian species were analysed on Western blots using monospecific human antibodies. In contrast to the 60-kD Ro and the La antigens which are well conserved in evolution, the 52-kD Ro antigen could be detected in primate cells only by this immunological approach. PMID- 1914241 TI - Chloride ion ingested with sodium affects the development of cerebral lesions in stroke-prone spontaneously hypertensive rats. AB - 1. To determine the effect of chloride ion on the development of hypertension and the incidence of cerebral lesions in stroke-prone spontaneously hypertensive rats (SHRSP), groups of 10 rats were administered chronically with either 171 mmol/L sodium chloride or equimolar sodium provided as sodium citrate in the drinking water from the age of 12 weeks. 2. The life span was significantly extended in SHRSP given sodium citrate (336 +/- 28 vs 246 +/- 26 days, mean +/- s.e.m., P less than 0.05) but their development of hypertension was not different from SHRSP given sodium chloride. 3. In order to determine the role of calcium homeostasis, calcium in urine was collected. Urinary calcium in SHRSP given sodium citrate was significantly decreased (1.0 +/- 0.12 vs 1.8 +/- 0.18 mg/24 h urine, P less than 0.05). 4. If the normal life span is 320 +/- 35 days, this suggests that chloride ion ingested with sodium accelerates the development of cerebrovascular diseases, and that increased urinary calcium excretion may be related to this adverse chloride effect on the development of hypertension in SHRSP. PMID- 1914242 TI - L-nitroarginine increases blood pressure in the rat. AB - 1. Effects of administration of NG-nitro-L-arginine (NO2Arg), a guanidino nitroarginine derivative, for 1 week on blood pressure and some vascular responses of rats were studied. 2. A significant rise of the systolic blood pressure was observed after the administration of NO2Arg with food (0.023% in weight, about 2.8 mg of NO2Arg per rat per day). Relaxation by acetylcholine decreased markedly in ring preparations of the thoracic aorta of NO2Arg-treated rats. However, glyceryltrinitrate-induced relaxation was not reduced after NO2Arg administration, suggesting that NO2Arg administration specifically inhibited endothelium-dependent relaxation. 3. An increase of blood pressure may be because oral administration of NO2Arg inhibited endothelium-dependent relaxation in vivo suggesting that the release of EDRF is important in physiological control of blood pressure. PMID- 1914243 TI - Secretion of medullipin I by isolated kidneys perfused under elevated pressure. AB - 1. Medullipin I (Med I) is a hormone extracted from renal papillae and its renomedullary interstitial cells (RIC). Med I is stimulated by elevation of the renal artery perfusion pressure. 2. When isolated normal rat kidneys were perfused either with oxygenated blood or with 5% albumin bubbled with O2 at elevated perfusion pressures, Med I appeared to be secreted into the renal venous effluent (RVE). Addition of Tween 20, treatment of the assay rat with SKF 525A, inhibitor of cytochrome P-450 and removal of the liver from the systemic circulation prevented vasodepression of both the RVE and extracted Med I. The lipid in the RVE gave the same dose-response as extracted Med I. 3. Lowering the renal artery perfusion pressure below normal inhibited the secretion of Med I. As the perfusion pressure was elevated Med I secretion appeared to increase. 4. Previous observations and the present study support the view that the renin angiotensin system and the Medullipin system are double feedback systems involved in blood pressure control. PMID- 1914244 TI - Effect of gonadotropins and pregnancy on prorenin and renin in the rat. AB - 1. Stimulation of adult female rats with pregnant mare serum gonadotropin (PMSG) and human chorion gonadotropin (hCG) increased active plasma renin about two fold, but caused only a slight increase of plasma prorenin. The concentrations of active renin and prorenin in the ovaries, and active renin in the uterus all increased about two-fold 2 days after stimulation with PMSG. The prorenin in the uterus was below detection in unstimulated rats and did not change consistently after PMSG. 2. Active renin and prorenin in plasma were unchanged in relation to pregnancy, except for a slight decrease of prorenin in the third trimester. In the first and third trimester the concentration in the ovaries of active renin and prorenin was decreased to about one-third of that in normal female rats. In contrast active renin in the uterus was increased about two-fold in the first trimester, whereas prorenin did not change consistently. 3. Our results confirm that gonadotropins and pregnancy affect the renin-angiotensin system in rats. However, the changes in the plasma seem to be much smaller than those previously reported in humans. Accordingly, our results do not support a systemic role of prorenin for reproduction in the rat. PMID- 1914245 TI - Effect of reserpine on catecholamine contents and met-enkephalin and beta endorphin levels in the hypothalamus and the pituitary. AB - 1. The effects of reserpine treatment on the contents of catecholamines and opioid peptides have been studied in the rat hypothalamus and pituitary. 2. Hypothalamic and pituitary catecholamines were drastically depleted following acute reserpine treatment. 3. Reserpine treatment also resulted in a significant decrease in immunoactive met-enkephalin content in both the hypothalamus (25%) and the anterior lobe (50%), but not in the neurointermediate lobe of the pituitary. 4. No changes were observed in immunoactive beta-endorphin levels. 5. These findings suggest that the met-enkephalin contents in the hypothalamus and the anterior pituitary may be under catecholaminergic control. 6. The lack of effect of acute reserpine treatment on immunoactive beta-endorphin contents might be due to the opposing effects of adrenergic and dopaminergic mechanisms. PMID- 1914246 TI - Diltiazem and verapamil lower blood pressure in the unanaesthetized rat through CNS mechanisms involving endogenous opioids. AB - 1. To evaluate and compare the effects of the calcium channel blockers, diltiazem and verapamil, on CNS modulation of blood pressure, unanaesthetized and unrestrained rats with catheters previously inserted into the lateral cerebral ventricle and femoral artery received intracerebroventricular (i.c.v.) administration of diltiazem or verapamil, 10 or 50 micrograms/kg, or their diluent. 2. Diltiazem, at both 10 and 50 micrograms/kg i.c.v., produced significant (P less than 0.05) decreases in systolic and diastolic blood pressure and heart rate. Verapamil, at 50 micrograms/kg but not at 10 micrograms/kg i.c.v., produced a significant (P less than 0.05) decrease in blood pressure, while both doses significantly (P less than 0.05) decreased heart rate. 3. To examine the endogenous opioid systems as potential modulators of the effects of these calcium antagonists, the mu opioid antagonist naloxone, 20 micrograms/kg, was administered i.c.v. either before or after each calcium antagonist. Naloxone reversed and prevented the reduction in blood pressure produced by both agents. The decrease in heart rate produced by verapamil but not diltiazem was reversed by naloxone. 4. The results suggest that: (1) calcium channels in neuron membranes in the CNS play a role in blood pressure regulation; (2) at least part of the blood pressure reduction produced by calcium blockers may be effected in the CNS; and (3) central opioid mechanisms modulate part of the action of the calcium antagonists verapamil and diltiazem on blood pressure. PMID- 1914247 TI - Effect of tolerance to glyceryl trinitrate on vascular responses in conscious rabbits. AB - 1. The effect of tolerance to glyceryl trinitrate (GTN) on vasodilator and vasoconstrictor responses was examined in conscious rabbits and isolated rabbit aortic rings. 2. In conscious rabbits, depressor responses to 5 min infusions of GTN (10-40 micrograms/kg per min intravenously (i.v.)), sodium nitroprusside (SNP, 5-20 micrograms/kg per min i.v.) and acetylcholine (ACh, 3-12 micrograms/kg per min i.v.) were examined before and after transdermal treatment with GTN (20 mg/48 h). GTN pretreatment significantly attenuated GTN-induced depressor responses, indicating the development of tolerance, but did not affect the reductions in arterial pressure induced by SNP or ACh. 3. Similarly, aortic rings taken from GTN pretreated rabbits exhibited tolerance to GTN but the relaxant responses to SNP or the calcium ionophore A23187 were not affected. In the aortic rings from GTN-tolerant rabbits contractile responses to serotonin or the thromboxane-mimetic U46619 were significantly attenuated, in contrast to the responses to the alpha 1-adrenoceptor agonist phenylephrine (PE) which were significantly enhanced. 4. Similarly, in conscious rabbits, PE-induced increases in arterial pressure and hindlimb vascular resistance were significantly enhanced by GTN pretreatment but the responses to the alpha 2-adrenoceptor agonist BHT 920 were unaffected. 5. In conclusion, tolerance to GTN does not affect endothelium dependent vasodilatation but does cause a selective enhancement of alpha 1- but not alpha 2-adrenoceptor-mediated vasoconstriction. PMID- 1914248 TI - Direct and indirect stimulation of pancreatic exocrine secretion by neurotensin in anaesthetized dogs. AB - 1. The effects of neurotensin on pancreatic exocrine secretion were investigated both in the intact whole pancreas and in the isolated, blood-perfused pancreas ex vivo in anaesthetized dogs. 2. Intravenous (i.v.) injections of neurotensin (0.01 1 nmol/kg) elicited dose-dependent increases in the secretory rate of pancreatic juice without changes in plasma levels of cholecystokinin (CCK). The concentration of bicarbonate in the pancreatic juice induced by neurotensin was increased, but the protein concentration was scarcely changed. 3. The neurotensin induced secretion was inhibited by SCH23390, a dopamine D-1 antagonist, but not by domperidone, phentolamine, propranolol, atropine, cimetidine, or L-364,718, a CCK antagonist. 4. Intra-arterial (i.a.) injections of neurotensin (0.1-3 nmol/kg) also elicited dose-dependent increases in the secretory rate of pancreatic juice flow, but did not change bicarbonate or protein concentration. The secretory activities were less effective and 1 nmol/kg of neurotensin i.a. was approximately equal to that of 0.03 nmol/kg of neurotensin i.v. 5. These results suggest that neurotensin mainly stimulates pancreatic secretion by acting indirectly. Neurotensin-induced secretion is, at least in part, mediated by endogenously released dopamine which activates dopamine D-1 receptors on the pancreas. In addition to its indirect action, neurotensin has a weak direct action to stimulate pancreatic secretion. PMID- 1914249 TI - Metabolic basis of catecholamine-induced water transport in everted gut sacs of mouse. AB - 1. Catecholamine-induced water transport was measured using an everted gut sac technique. Adrenaline, noradrenaline and isoprenaline induce dose-dependent increases in water transport by the proximal intestinal sacs. Use of selective adrenergic agents revealed the possible involvement of alpha 1- and beta 2 receptors in mediation of catecholamine stimulation of water transport in this segment. 2. Inhibition of glycolysis reduced the effect mediated through alpha 1 receptors, while the inhibition of oxidative phosphorylation blocked the beta 2 receptor mediated increase in water transport. 3. Basal transport of water was also significantly reduced by inhibition of glycolysis but was significantly elevated by blockage of oxidative phosphorylation. 4. Suppression or stimulation of glycolysis was paralleled by similar changes in lactic acid release from the gut wall. 5. It is concluded that the energy for the catecholamine-induced water transport is contributed by glycolysis and oxidative phosphorylation coupled to alpha 1- and beta 2-receptors, respectively. Under basal conditions water transport is mainly dependent on glycolysis in the segment of intestine examined. PMID- 1914250 TI - Effects of torasemide on renal haemodynamics and function in anaesthetized dogs. AB - 1. We examined the effects of torasemide (0.3 and 1 mg/kg i.v.) on renal haemodynamics and function employing renal clearance and stop-flow techniques in anaesthetized dogs and compared these with furosemide (1 and 3 mg/kg i.v.). 2. Torasemide and furosemide did not influence renal haemodynamics, in the renal clearance study, but caused a dose-related and significant increase in urine flow and urinary excretion of sodium and potassium. Torasemide and furosemide increased fractional excretion of sodium in the distal tubules with a relatively small increase in the fractional excretion of lithium (index of sodium excretion at the proximal tubules, FELi). The diuretic profile of torasemide was of long duration, compared with that of furosemide. 3. Torasemide and furosemide inhibited sodium reabsorption at the distal portion of the tubules in the stop flow study. 4. It is suggested from these results, that the main diuretic site of action of torasemide is the ascending limb of the loop of Henle. PMID- 1914251 TI - Lack of sympathetic augmentation in response to intravenous load of glucose in rabbits. AB - 1. We investigated a link between sympathetic nervous function and carbohydrate metabolism by measuring renal sympathetic nerve activity in response to intravenous load of glucose in alpha-chloralose-urethane anaesthetized rabbits. 2. Intravenous infusion of a 25% glucose solution (0.5 g/kg) over 3 min caused a transient increase in arterial blood pressure and a decrease in renal sympathetic nerve activity. Thereafter, these parameters were restored and remained around preload levels while plasma glucose and insulin concentrations were still elevated. 3. Equimolar mannitol solution produced similar patterns of change in blood pressure and nerve activity without an elevation of plasma glucose and insulin levels. 4. The transient changes in blood pressure and renal nerve activity could be attributed to acute hypervolaemia indicated by similar changes in plasma osmolality and haematocrits in the two groups of treatment. 5. The present study did not support a close relationship between carbohydrate metabolism and the sympathetic nervous system regulating cardiovascular function. PMID- 1914252 TI - Activation of Na+/H+ exchange is unnecessary in the induction of c-fos mRNA in serum-stimulated vascular smooth muscle cells. AB - 1. The effects of extracellular Na+ concentration ([Na+]o) on serum-stimulated c fos mRNA induction in vascular smooth muscle cells (VSMC) were studied to examine whether the activation of Na+/H+ exchange and the following intracellular alkalinization are necessary in the induction of c-fos in VSMC. 2. When monitored with 2', 7'-bis (carboxylethyl)-5(6)-carboxyfluorescein, the reduction in [Na+]o in HCO(3-)-free buffer caused a dose-dependent inhibition of Na(+)-dependent intracellular pH recovery in acid-loaded VSMC. In addition, serum-stimulated intracellular alkalinization in VSMC was completely blocked by the removal of extracellular Na+. 3. By contrast, c-fos induction, quantified by slit blot hybridization of c-fos mRNA, was not fully inhibited by the reduction of [Na+]o. Furthermore, amiloride and ethylisopropyl-amiloride, inhibitors of Na+/H+ exchange, only partially blocked c-fos induction by serum. 4. We concluded from the observation above, that the intracellular alkalinization caused by the activation of Na+/H+ exchange was unnecessary in serum-stimulated induction of c fos mRNA in VSMC. PMID- 1914253 TI - Urinary excretion of prostanoids during sleep in obstructive sleep apnoea patients. AB - 1. Given the unexplained frequent association between systemic hypertension and obstructive sleep apnoea (OSA), the secretion of prostanoids during sleep was investigated (more specifically, the ratio of prostacyclin (PGI2) to thromboxane A2 (TxA2), since they have marked opposite effects on vascular tone). Prostacyclin has vasodilating effects, whereas thromboxane results in vasoconstriction. 2. In 11 OSA drug-free male patients (age 53 +/- 2 years, mean +/- s.e.m.; apnoea index 55 +/- 15 apnoeas/hour of sleep; body mass index 31 +/- 2 kg/m2), we measured the urinary excretion during sleep of 6-keto-PGF1-alpha and of thromboxane TxB2 (the stable metabolites of prostacyclin PGI2 and of thromboxane A2 respectively). This was done on two consecutive nights; one untreated, the other with nasal continuous positive airway pressure (CPAP) treatment. The results were compared with those of nine normal unobese male subjects. 3. The urinary ratio of 6-keto-PGF1-alpha to TxB2 was significantly (P less than 0.001) lower in the untreated OSA patients (1.7 +/- 0.2) than in the controls (3.1 +/- 0.3). It significantly increased with CPAP treatment to 2.3 +/- 0.2, P less than 0.02, which was no longer different from the controls. 4. These results suggest that OSA is associated with an abnormal release of prostanoids during sleep resulting in a decrease of the prostacyclin to thromboxane ratio which potentially has a vasoconstricting effect. The relationship between these changes and the systemic hypertension often observed in OSA patients remains to be established. PMID- 1914254 TI - Development of tolerance to kava in mice. AB - 1. The development of tolerance to the aqueous extract of kava, and to the lipid soluble extract (kava resin) was tested in mice. 2. Tolerance to the unknown pharmacologically active ingredient(s) developed very rapidly, given parenterally, in the aqueous extract. A minimally effective daily dose (50 mg/kg) of the aqueous extract for 3 days was sufficient to produce tolerance to a test dose of 150 mg/kg, which is close to the ED50. As tolerance was evident at the first test period it can be assumed to be physiological tolerance. 3. Kava resin decreased spontaneous motility and caused a loss of muscle control. A minimally effective daily dose of kava resin (100 mg/kg) did not produce tolerance to the above effects of a weekly test dose of kava resin (166 mg/kg) within 7 weeks. In a further experiment the dose was raised to 150 mg/kg twice daily and this schedule caused partial tolerance to occur within 3 weeks, but very little further tolerance developed over the ensuing 2-week period. 4. To try to induce learned (behaviourally acquired) tolerance a dose of 166 mg/kg kava resin was injected daily and animals were tested each day while under the influence of the drug. However, even under these conditions, there was no tolerance evident within 3 weeks, when the experiment was terminated. 5. It appears difficult to induce the development of physiological or learned tolerance to kava resin in mice. PMID- 1914255 TI - Anti-ischaemic and vasospasmolytic effects of a novel Ca2+ channel blocker, SD 3211, in vitro. AB - 1. The present study was undertaken to determine the vasospasmolytic activity of a novel non-dihydropyridine type of Ca2+ channel blocker, SD-3211, in isolated canine coronary arteries and its ability to reduce myocardial ischaemic damage in isolated perfused rabbit hearts. 2. The vasospasmolytic effect of SD-3211 was investigated using 3,4-diaminopyridine-induced rhythmic contraction, in comparison with its enantiomer (SD-3212), nicardipine and diltiazem. SD-3211 was shown to reduce the peak tension and increase the contraction frequency. The order of potency for the relaxation of the peak tension was as follows: nicardipine greater than SD-3211 greater than diltiazem greater than SD-3212 and being compatible with that for the relaxant effects of these compounds on KCl induced contraction in the same specimen. 3. Furthermore, the effect of SD-3211 on myocardial damage due to global ischaemia for 60 min followed by 60 min of reperfusion was examined. SD-3211 at a concentration of 2 X 10(-8) mol/L was given for 40 min before and again for 60 min after the ischaemia. SD-3211 attenuated the increase in leakage of creatine phosphokinase from the hearts and the decrease in pH of perfusate during reperfusion, while concomitantly providing a significant improvement in the post-ischaemic recovery of developed tension. 4. These results suggest that SD-3211 has properties to reduce coronary vasospasm and to provide protection against ischaemic damage, both of which may have beneficial actions in the treatment of ischaemic heart disease. PMID- 1914256 TI - Rheumatogenic streptococci and autoimmunity. AB - The uniqueness of the group A streptococcus in initiating a cardiodestructive disease in a limited segment of the human species, regardless of race or ethnic group, makes the quest for a unique host response to a specific streptococcal antigen an intriguing and persisting challenge for clinical investigators, particularly for those investigators interested in autoimmunity. New methodology is making possible more incisive research approaches. The defined streptococcal antigens that turn out to be epitopes identical with host tissues, such as the M protein/cardiac myosin model or the hyaluronate in the capsule of mucoid rheumatogenic strains, offer the opportunity for more incisive clinical investigations. The isolation and cultivation of cardiotoxic T cell clones directed against such epitopes shared by host and parasite may eventually be possible. We may then learn more about whether autoimmunity is indeed a factor in the pathogenesis of rheumatic heart disease. PMID- 1914257 TI - Low interleukin-2 synthesis by type 1 diabetics is regulated at the pretranslational level. AB - Insulin-dependent diabetes mellitus (IDDM) is believed to be a consequence of an autoimmune attack on beta cells by T cells. We have previously reported that T cells from the majority of patients with IDDM produced decreased levels of interleukin-2 (IL-2) following activation with phytohemagglutinin. In this study we began to characterize the basis for this defect. First, we tested whether the decreased IL-2 synthesis was due to the secretion of a factor which inhibited the ability of indicator cells to respond to IL-2 or which inhibited IL-2 release by responder cells. Second, we examined steady-state levels of IL-2 mRNA in IDDMs and controls. To make this feasible, given the limited number of peripheral blood lymphocytes (PBL) available from our patients, we depended upon an approach which enabled the generation of large numbers of resting T cells, called G0/G1 cells, from small numbers of PBL. Preliminary experiments demonstrated that G0/G1 cells from IDDMs reproduced the IL-2 defect seen originally with PBL. Our results suggested that the secretion of inhibitory factors could not explain the IL-2 defect. A comparison of steady-state levels of IL-2 mRNA from activated T cells of IDDMs and age-matched controls, however, demonstrated lower levels of IL-2 mRNA in IDDMs compared to controls. Finally, we observed that the IL-2 mRNA in IDDM T cells was less stabile than that in the control cells, suggesting a possible mechanism for the defect. PMID- 1914258 TI - Infection of "nonprofessional phagocytes" with Mycobacterium avium complex. AB - Organisms belonging to the Mycobacterium avium complex are the most common bacteria isolated from patients with AIDS. In these patients, M. avium is associated with disseminated disease, and bacteria are found within macrophages in the liver and spleen. To examine the potential of M. avium infection of a nonprofessional phagocyte, the murine fibroblast cell line (L929 cells) are infected with strain 101 (serotype 1) of M. avium. The duplication time for the intracellular bacteria was approximately 36 hr. Progressive intracellular growth ultimately resulted in the destruction of infected cells (after approximately 12 days in culture). Supernatant obtained from infected L929 cells contained interferon-beta (IFN beta) and granulocyte macrophage colony stimulating factor (GM-CSF) (50 +/- 12 ng/10(5) cells and 63 +/- 18 pg/10(5) cells, respectively, by 18 hr). IFN beta could be detected by 3 hr after infection, while GM-CSF was first detected by 6 hr. Release of IFN beta by infected L929 cells could subsequently stimulate NK cells, but not macrophages, to lyse infected L929 cells. These data using L929 cells suggest that M. avium may invade fibroblasts during the course of the infection and that fibroblast infection may trigger NK cell-mediated cytotoxicity against the infected fibroblasts. PMID- 1914259 TI - Cytokine production in vitro and the lymphoproliferative defect of natural measles virus infection. AB - In natural measles virus infection, evidence of intense immune system activation is present simultaneously with clinically relevant immune suppression. While evidence of activation is most prominent early in the disease, skin test responses and in vitro lymphoproliferation are depressed for weeks after the onset of the rash. It is not known whether the prolonged period of reduced immune responsiveness results from a single defect or a succession of different abnormalities. To gain further insight into measles-induced immune suppression we studied the production of soluble IL-2 receptor (sIL-2R), interferon-gamma (IFN gamma), IL-1 beta, and tumor necrosis factor (TNF alpha) by peripheral blood mononuclear cells (PBMC) isolated from measles patients at various times after the onset of the rash. Studies included addition of supplemental recombinant IL-1 beta (rIL-1 beta) or recombinant IL-2 (rIL-2) or suppression of prostaglandin synthesis by indomethacin (IM). Proliferation in response to phytohemagglutin (PHA) was abnormal at all stages of disease. During the acute phase (first week after the onset of the rash) spontaneous production of sIL-2R was increased (76 +/- 54 vs. controls 4 +/- 4; P less than 0.03), suggesting in vivo T cell activation while PHA-induced sIL-2R was decreased (228 +/- 43 vs. control 582 +/- 127; P less than 0.002), suggesting that the capacity to produce IL-2 in response to mitogen was limited. Supplementation of PHA-stimulated cultures with rIL-2 improved but did not normalize both proliferation (58,600 +/- 4900 to 70,700 +/- 4400 vs. control 97,700 +/- 15,500; P less than 0.03) and sIL-2R levels (114 +/- 58 to 309 +/- 87 vs. control 582 +/- 127; P less than 0.003). Both spontaneous (25 +/- 18 vs. control 237 +/- 92; P less than 0.002) and PHA-induced (20 +/- 20 vs. control 604 +/- 129; P less than 0.004) TNF alpha levels were subnormal and were not improved with rIL-2, rIL-1 beta, or IM, suggesting a block in monocyte TNF alpha production. Spontaneous and PHA-induced IFN-gamma and IL-1 beta levels were normal. During the convalescent phase (greater than 2 weeks after the onset of the rash), spontaneous levels of sIL-2R were normal and PHA-induced levels were completely normalized with supplemental rIL-2 but proliferation remained below normal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1914261 TI - The pathogenetic pathways of oral lichen planus--a review. PMID- 1914260 TI - Autoantibodies to the collagen-like region of C1Q deposit in glomeruli via C1Q in immune deposits. AB - The autoantibodies to the collagen-like region of C1q (CLR), purified from two patients with systemic lupus erythematosus, deposited in mouse glomeruli when human C1q was present in antigen-antibody complexes in glomeruli. The immune deposits with C1q in mouse glomeruli were achieved by the administration of cationized immune complexes containing human C1q. The presented data suggest that the autoantibodies to CLR could enhance the pathogenic role of immune complexes deposited in glomeruli by binding to C1q in immune deposits. These findings may explain the association of autoantibodies to CLR with proliferative lupus nephritis. PMID- 1914262 TI - Dental manpower demography in Israel--Part I. PMID- 1914263 TI - Breakthrough in dentistry: computerized technology--the Cerec system. PMID- 1914264 TI - Neurofibromatosis with orbital involvement--review of literature and case reports. PMID- 1914265 TI - Further thoughts about access to cardiovascular care. PMID- 1914266 TI - Management of coronary heart disease in the elderly. AB - The prevalence of coronary heart disease (CHD) increases rapidly with advancing age and remains the major cause of death among elderly Americans. The number of elderly has doubled in the last 30 years and is projected to continue growing at more than twice the rate of the general population. The resources required in managing CHD in this population will reach astronomical levels during the next few decades and will severely tax our ability to provide adequate medical care to all citizens, unless cost effective diagnostic and therapeutic strategies are developed which do not severely compromise health care. Risk factors for CHD should be identified and modified as early in life as possible. Modification of risk factors begun at advanced age appears to confer benefit, however. Anti ischemic drug therapy is the treatment of choice for patients with mild or moderate stable angina. Select elderly may be willing to accept the increased risks of coronary revascularization to achieve relief from debilitating angina or prolongation of life. Physicians must use care in planning diagnostic and therapeutic strategies. Quality of life and independence are often more important considerations than longevity in this age group. PMID- 1914267 TI - Effects of sublingual nitroglycerin in patients receiving transdermal nitroglycerin for coronary artery disease: prevention of cross-tolerance. AB - The systemic hemodynamic and coronary dilative responses to sublingual nitroglycerin were studied in patients receiving transdermal nitroglycerin. A total of 48 patients with coronary artery disease were divided into 4 groups: 12 patients receiving 1 tablet of sublingual nitroglycerin without transdermal nitroglycerin (Group 1), 12 patients receiving 1 tablet of sublingual nitroglycerin with 12-hour-daily intermittent therapy of transdermal nitroglycerin (Group 2), 12 patients receiving 1 tablet of sublingual nitroglycerin with continuous therapy of transdermal nitroglycerin with continuous therapy of transdermal nitroglycerin (Group 3), and 12 patients receiving 2 tablets of sublingual nitroglycerin with continuous therapy of transdermal nitroglycerin (Group 4). Before and during administration of sublingual nitroglycerin, aortic pressure, left ventricular pressure, and coronary artery diameter were examined at diagnostic cardiac catheterization in all patients. During sublingual nitroglycerin, the decreases of aortic systolic pressure and left ventricular end-diastolic pressure were greater in Group 1, 2, and 4 than in Group 3. Dilation of coronary arteries by sublingual nitroglycerin tended to be greater in Group 1, 2, and 4 than in Group 3. Thus, the effects of sublingual nitroglycerin for the relief of ischemia might be more prominent in patients with intermittent therapy of transdermal nitroglycerin than in those with continuous therapy. The increased dose of sublingual nitroglycerin for the relief of ischemia might be more effective in patients with continuous therapy of transdermal nitroglycerin. PMID- 1914268 TI - Changes in left atrial size in patients with lone atrial fibrillation. AB - A retrospective analysis was performed on 23 subjects with lone atrial fibrillation who were followed for an average of 6.2 years (1.1-12.8 years). In all patients, underlying organic heart disease was excluded based on history, physical exam, electrocardiogram, echocardiogram, and Doppler ultrasound interrogation. All patients had at least two echocardiographic studies during the period of observation. Atrial fibrillation was chronic in 11 subjects and paroxysmal in 12. All echocardiographic measurements were obtained by averaging the measurements of two blinded investigators. Left atrial size increased an average of 5.6 mm which translates into a 14.7% increase over the baseline measurement. This increase in size was not associated with a change in left ventricular mass or fractional shortening as determined by echocardiography. Subjects with chronic atrial fibrillation had a larger percent increase than subjects with paroxysmal atrial fibrillation (18.9 vs. 10.8%), although this relative change in size failed to reach statistical significance. The only variable which significantly contributed to the change in left atrial size was the duration of follow-up. We conclude that atrial fibrillation occurring in patients with lone atrial fibrillation may cause a slow and progressive increase in left atrial size independent of changes in left ventricular size or function. PMID- 1914269 TI - Left ventricular diastolic filling in patients with coronary artery disease without myocardial infarction. AB - Left ventricular diastolic dysfunction at rest was studied in 24 patients with coronary artery disease but no evidence of previous myocardial infarction. Seven patients with normal coronary arteries were studied as control. Diastolic filling was analyzed by the serial left ventricular volume and 14 radial axes from the gravity point of the left ventricle with cine left ventriculography. There were no differences in the systolic function between coronary artery disease and the normal control. Peak filling rate was decreased significantly in the groups with left anterior descending artery disease (LAD, p less than 0.05) and multivessel disease (MVD, p less than 0.05), but not in the group with right coronary artery disease (RCA). Time to peak filling rate was prolonged in each group of LAD (p less than 0.05), RCA (p less than 0.05), and MVD (p less than 0.001), compared with controls. The time-volume curve showed disturbed rapid filling in the LAD and RCA groups, and also both depressed rapid and slow filling in the MVD group. In the LAD group, the filling fraction was decreased significantly at the time of 25% of the diastolic period (p less than 0.001) and radial distension to the anterior wall was decreased at the time of 25%, 50%, and 75% of the diastolic period, compared with controls. In the RCA group, the filling fraction (p less than 0.001) and radial distension to the posterior wall were decreased only at the time of 25% of the diastolic period. In the MVD group, filling fraction and radial distension to the most wall were decreased at 25%, 50%, and 75% of the diastolic period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914270 TI - Left ventricular function during transient coronary occlusion: digital subtraction left ventriculograms during coronary angioplasty. AB - The impact of transient myocardial ischemia on left ventricular function was examined by digital subtraction left ventricular angiography. Contrast medium was injected into the right pulmonary artery before, at 60 seconds of balloon inflation, and 10 minutes after balloon deflation. A total of 69 patients completed the study. In 52 patients, the left anterior descending artery (LAD) was involved, and in 17, the right coronary artery (RCA) was the focus. Ejection fraction (EF) declined by balloon inflation and returned to baseline value after deflation of the balloon. There was tendency toward a lower EF and wider akinetic area for LAD dilatation. The linear correlation between resting EF and EF during balloon inflation suggested that the effect of momentary coronary occlusion on left ventricular function appears to be additive to pre-existing left ventricular dysfunction, and resting ejection fraction is an important parameter for estimating the degree of diminished left ventricular function during myocardial ischemia. PMID- 1914271 TI - Relationship of auscultatory fourth heart sound to the quantitated left atrial filling fraction. AB - The fourth heart sound (S4) has been associated with vigorous atrial contraction. However, the presence of S4 has not been previously correlated with quantitated left atrial filling fraction. In this study, the presence of an auscultatory S4 was compared with the Doppler echocardiographically quantitated left atrial filling fraction in 41 consecutive patients in whom S4 was judged to be present or absent according to the consensus of cardiologists. Left atrial filling fraction in patients with S4 was 49% and was significantly greater than 33% found in patients without S4 (p less than 0.005). Using atrial filling fraction of 35% as a dividing line, S4 had a sensitivity of 84% and a specificity of 75% for determining left atrial filling fraction greater than or equal to 35%. Furthermore, of 25 patients with S4, 21 (84%) had atrial filling fraction greater than or equal to or less than 35%, and of 16 patients without S4, 12 (75%) had atrial filling fraction less than 35%. Thus, the presence or the absence of S4 is quantitatively related to the left atrial filling fraction and appears to predict atrial filling fraction greater than or equal to or less than 35% reasonably well. PMID- 1914272 TI - A large-scale trial of captopril for mild to moderate heart failure in the primary care setting. AB - A large-scale, prospective, 8-week, office-based study was conducted to evaluate the effects of adding captopril to a therapeutic regimen of diuretic and digoxin or diuretic alone in the management of patients with mild to moderate congestive heart failure (CHF). A total of 2218 primary care physicians evaluated 6669 patients over the study period for efficacy parameters, which included changes in a modified New York Heart Association (NYHA) functional classification, symptomatology, and daily activity levels. Overall, 63.8% of evaluated patients improved with regard to functional ability, with 19% improving two or more modified NYHA classes. Symptoms of CHF, including dyspnea on exertion, fatigue, and orthopnea and signs, including rales and peripheral edema, were reduced in 86% of these patients: 41.5% demonstrated mild improvement; 30.0%, moderate improvement; and 14.5%, marked improvement. Three parameters, with which patients reported having difficulty at study entry, were assessed serially to evaluate changes in functional capacity; 78.5% of patients reported an increased walking distance, 72.3% had increased capacity for climbing stairs, and 60.2% had improved capacity for individual recreational activities. Adverse experiences were reported in 18.1% of all patients; 4.9% of patients withdrew from the study because of an adverse effect. Combination therapy with captopril and diuretic for CHF was shown to be safe and effective regardless of patient age (less than 70 years vs. greater than or equal to 70 years), duration of heart failure (less than 1 year vs. greater than 1 year), presence of digoxin treatment, or the dosing schedule employed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914273 TI - Heart rate variability: an important new risk factor in patients following myocardial infarction. AB - After acute myocardial infarction, cardiac autonomic, and particularly parasympathetic, activity decreases, followed by a gradual return toward normal over the next few weeks and months. The easiest measurable index of autonomic activity is heart rate variability, which can be assessed in a number of different ways. Where heart rate variability is low after myocardial infarction, long-term survival is considerably reduced, independent of other known risk factors. This may be caused by patchy autonomic denervation, rendering the heart more susceptible to potentially fatal arrhythmias. Prophylactic drug therapy might reduce mortality in patients with low heart rate variability. PMID- 1914274 TI - Catheter balloon valvuloplasty of stenotic porcine bioprosthetic valves: Part I: Anatomic considerations. AB - During the last several years, dilating balloons have been applied in the treatment of stenotic cardiac valves. This interest has recently been extended to stenotic porcine bioprosthetic valves. Part I of this review discusses the pathologic processes responsible for degeneration of porcine prostheses: intrinsic calcification (mineralization), cuspal tears and perforations, and cuspal thrombosis (non-infective). These changes form the basis of applied balloon valvuloplasty techniques. PMID- 1914275 TI - Familial recurring cardiac myxoma. AB - A 34-year-old woman presented with her fourth occurrence of an atrial myxoma and a right lower lung field mass. Her surgical history was extensive. In addition to resection of three previous atrial myxomas, she had undergone resection of her adrenal glands as a teenager because of Cushing's syndrome, and a hysterectomy at age 26 revealed a myxoid leiomyoma. Family history was remarkable as a maternal uncle and daughter died from embolic complications of left atrial myxomas and her sister previously had a left atrial myxoma resected. The patient underwent uncomplicated removal of the myxoma, and resection of the lung mass revealed a granuloma. A review of typical and atypical aspects of cardiac myxomas is provided including a rare and recently described syndrome of familial cardiac myxoma associated with Cushing's syndrome, spotty skin pigmentation and other myxoid tumors. PMID- 1914276 TI - Life-threatening ventricular tachycardia as the presenting symptom of metastatic cardiac disease. AB - We present 2 cases in whom repetitive rapid ventricular tachycardia (VT) was the initial manifestation of metastatic cardiac disease. In one patient, repetitive VT appeared during chemotherapy for stage IV paratesticular rhabdomyosarcoma which led to the diagnosis of cardiac metastases. In the other, it led to the diagnosis of malignant pericardial effusion 17 years after successful therapy for a breast carcinoma. In conclusion, in patients with present or past history of malignancy, the appearance of life-threatening VT should raise the suspicion of cardiac metastases. PMID- 1914278 TI - Jeremiah Stamler. AB - Jeremiah Stamler has had a major impact on the primary and secondary prevention of cardiovascular disease. His work began in the animal experimental laboratory and shifted to large-scale epidemiologic studies and clinical trials, resulting in nearly 800 contributions to the world medical literature. His influence is felt, not only through these publications and his innumerable lectures, but also... "through the hundreds of young people he has helped train (in the U.S. and abroad), and through the leadership role he has played locally, nationally, and internationally in preventive cardiology... The spirit imbuing the work of Dr. Stamler is a deep concern for human welfare, for the prevention of unnecessary disease, and for the prolongation of healthy life. This same spirit has made his name synonymous also with preservation of civil liberties, international cooperation among scientists of all countries, and efforts to avoid the catastrophe of nuclear holocaust." According to Dr. Geoffrey Rose, Dr. Stamler "... confronted the most devastating health problem of Western Society, cardiovascular disease. He espoused the belief that diet holds the key to its control at a time when that belief was widely considered to be false and its proponents a little crazy. That is now accepted wisdom, and the fact that in many countries at last the problem is in decline is due to this man more than to any other." PMID- 1914277 TI - Coronary vasospasm as a potential cause of myocardial infarction and paroxysmal atrial fibrillation in a relatively young woman. AB - Vasospasm-related myocardial infarction in young women with normal coronary arteries has infrequently been reported and vasospasm-related paroxysmal atrial fibrillation (PAF) has rarely been described. We present a 33-year-old woman with old inferior myocardial infarction and postinfarction angina at rest; the angina was accompanied by PAF and electrocardiographic ST-segment elevation in the inferior leads. Coronary angiography revealed normal coronary arteries and intracoronary acetylcholine provoked an intense and diffuse spasm of the right and left coronary artery. The spasm of the right coronary artery was associated with PAF and ST-segment elevation in the inferior leads. Frequently documented PAF, accompanied by chest discomfort and ST-segment elevation in the inferior leads, was more effectively removed with isosorbide dinitrate than with disopyramide. These data suggest that coronary vasospasm is a likely cause of myocardial infarction and even PAF, although the precise mechanism leading to PAF remains unknown. PMID- 1914279 TI - Successful immunotherapy of murine melanoma metastases with 7-thia-8 oxoguanosine. AB - We have recently reported that a synthetic nucleoside, 7-thia-8-oxoguanosine (7T8OG) is a potent activator of a number of effectors which are involved in anti tumor immune responses. 7T8OG was found to induce interferon (IFN) production, to activate asialo-GM1 positive (AGM+1) killer cells, and to enhance specific antibody responses. In the present study, we investigated the effect of 7T8OG on growth of the murine pulmonary B16 melanoma and on formation of metastases. C57BL/6 mice were injected i.p. with 50-150 mg/kg 7T8OG before or after i.v. inoculation of B16 melanoma tumor cells, and 17-19 days after tumor inoculation, the number of metastases in the lungs were counted. 7T8OG given systemically in a single or a divided dose 24 h prior to the challenge of tumor cells reduced the number of lung tumor metastases by 89-99% which is highly significant as compared to untreated control (P less than 0.001). Occasional extra pulmonary tumor growth in the thoracic cavity and neck lymph node was also completely inhibited. The reduction in the number of tumor nodules was dose dependent. A single dose of 150 mg/kg of 7T8OG was also effective in inhibiting the growth of 3-5 day old metastatic tumors. The cytotoxic activity of killer cells induced in vivo by 7T8OG was completely abolished by in vitro treatment of cells with anti-AGM1 antibody plus complement. Administration of anti-AGM1 antibody following the 7T8OG treatment completely abrogated the anti-tumor effect of 7T8OG, resulting in a massive increase in the number of tumor foci in the lungs. Administration of carageenan or silica followed by injection of 7T8OG caused a significant increase (P less than 0.01) in the number of pulmonary tumor nodules compared to treatment with 7T8OG only. These findings indicate that activated macrophages or perhaps their cytokine (tumor necrosis factor) also contribute to the host tumor defense by 7T8OG. PMID- 1914282 TI - Prevention of deep vein thrombosis after total knee arthroplasty. Coumadin versus pneumatic calf compression. AB - The rate of deep vein thrombosis (DVT) after total knee arthroplasty (TKA) without prophylaxis has been reported as high as 84%. Coumadin anticoagulation and pneumatic calf compression (PCC) boots are two current therapies that have been thought to be effective in reducing this high rate of DVT. To investigate these two methods, a nonrandomized prospective study was designed. The first group involved treating 48 consecutive knee arthroplasties with a regimen of coumadin anticoagulation. The second group involved 81 consecutive knee arthroplasties treated with sequential PCC boots. Bilateral lower extremity venography was performed between the eighth and tenth hospital postoperative days. The overall incidence of DVT in the coumadin group was 33%, with 29% having calf thrombi and 6% having thigh thrombi. The overall incidence of DVT in the boot group was 31%, with 27% having calf thrombi and 6% having thigh thrombi. In both groups, there were no treatment-related complications. Cost analysis of the administration of each type of therapy showed coumadin to be approximately 50% more expensive than PCC boots. Although coumadin and PCC boot therapy are safe and effective in reducing the incidence of DVT after TKA, there are economic factors that make the latter a more favorable option. PMID- 1914281 TI - Organ-specific growth of a murine lymphoma of spontaneous origin in nude mice. AB - The MOC-25 tumour arose spontaneously in a female nude mouse and was established as a continuous line intraperitoneally in nude mice, where it reproduces the topological features of its origin, growing preferentially in the uterus, ovaries and liver. Karyotype analysis showed that MOC-25 cells are hyperdiploid. Tumorigenicity and malignant behaviour were studied by transplanting tumour cells into different sites in nude mice. The comparison of tumour take after i.p. and s.c. injections of scaled concentrations of MOC-25 cell suspension showed preferential growth in the peritoneum. Regardless of the route of implantation (s.c., i.v., i.p.), this tumour rapidly and preferentially disseminated to the liver, uterus, ovaries, spleen and bone marrow. No significant differences in tumour growth and metastatic behaviour were observed when MOC-25 was injected in ovariectomized nude mice or in male nude mice. Morphology studies using light and electron microscopy, immunophenotyping and molecular analysis indicated a B lymphoid origin of the MOC-25 tumour. PMID- 1914280 TI - Effects of gamma irradiation on cultured rat and mouse microvessel endothelial cells: metastatic tumor cell adhesion, subendothelial matrix degradation, and secretion of tumor cell growth factors. AB - The effects of gamma-irradiation on the properties of microvessel endothelial cells were studied in vitro. After incubating confluent endothelial cell monolayers in low serum-containing medium for 24 h, the monolayers were irradiated with 137Cs. Survival of rat lung microvessel endothelial (RLE) and mouse brain microvessel endothelial (MBE) cells were similar after irradiation (Do = 2.17 and 1.75 Gy, Dq = 4.44 and 5.67 Gy, and n = 7.8 and 25 for RLE and MBE cells, respectively). We examined the effects of gamma-irradiation on endothelial cell morphology, adhesion of syngeneic rat lung or mouse brain metastasizing tumor cells, release of the subendothelial matrix-degrading enzyme heparanase, and secretion of soluble mitogenic factors that stimulated the growth of syngeneic metastatic tumor cells. The effects of gamma-irradiation were not apparent until several hours after irradiation, and by 24 h doses of greater than or equal to 10 Gy caused limited endothelial cell retraction and reorganization of the endothelial monolayer. By 24 h after irradiation there was also increased adhesion of metastatic tumor cells to RLE but not MBE cells. We also examined the effects of gamma-irradiation on the release from endothelial cells of enzymes that solubilize the subendothelial matrix. Radiation resulted in a significant increase in the release of matrix-degrading enzyme (heparanase) that solubilized [35S]-labeled heparan sulfate from subendothelial matrix. This was most pronounced in the 24 h sample from gamma-irradiated endothelial cells. Finally, we examined the gamma-irradiation-induced release of mitogenic factors from endothelial cells that could stimulate the growth of metastatic cells in serum limiting medium. The medium from RLE but not MBE cells stimulated the growth of a rat mammary carcinoma cell line. The results suggest that gamma-irradiation of microvessel endothelial cells can affect the interactions of tumor cells with endothelial cells and their subendothelial matrix; these processes could facilitate metastasis formation in irradiated tissues such as the lung. PMID- 1914283 TI - Evaluation of total knee arthroplasty using isokinetic testing. AB - Although total knee arthroplasty (TKA) has been studied extensively, objective muscle testing has not been reported. Isokinetic testing of 68 patients with degenerative joint disease scheduled for unilateral TKA revealed that marked muscular deficits in flexion and extension were present preoperatively in the involved knee. Postoperatively, hamstring peak-torque values were able to attain strength levels of the uninvolved knee within the period of seven to 12 months after surgery, whereas the quadriceps mechanism still showed a residual deficit at two years follow-up evaluation. In addition, the ratio of flexion to extension peak torques in the operated knee returned to normal values as the quadriceps mechanism was rehabilitated. A comprehensive evaluation system consisting of Cybex II isokinetic testing, gait mat analysis, and the Hospital for Special Surgery knee rating scale is also presented. Isokinetic testing correlated well with gait analysis. Patients with a nearly balanced quadriceps-to-hamstring ratio walked with a more symmetrical gait pattern. The knee rating scale was less reliable in assessing functional outcome. Functional testing and evaluation at the authors' institution has provided an important source of objective information that allows better planning and evaluation of TKAs. These isokinetic studies enable more critical planning of the rehabilitation program. Hamstring or quadricep exercises may be emphasized as required. The authors conclude that a balanced hamstring to quadriceps mechanism is needed for resumption of normal gait. PMID- 1914284 TI - Results of revision total knee arthroplasty associated with significant bone loss. AB - The results of 40 revision total knee arthroplasties (TKAs) in 38 patients performed for aseptic failure with significant bone loss were reviewed. All knees were evaluated for at least two years, with an average of 41 months (range, two to nine years.) Seventy-five percent of the knees were considered excellent or good. Ten percent were considered failures. There were no infections. Overall complication rate was 30%, of which wound complications were the most common. Revision TKA remains demanding, but results can be improved by (1) restoring the mechanical alignment of the knee with accurate component positioning; (2) filling all bone defects with bone, cement, or modular spacers; (3) using stems to assist in component support; and (4) adherence to soft-tissue balancing and care. PMID- 1914285 TI - Implications of metallic corrosion in total knee arthroplasty. AB - Increasing concern about the effects of metallic release from prosthetic implants has developed in the past several years. This article serves to review the basic science of the effects of metallic corrosion products. The possible ramifications of metallic release in human studies and patients with prosthetic implants are presented. PMID- 1914286 TI - Bilateral total knee arthroplasty. One cruciate retaining and one cruciate substituting. AB - Thirty bilateral-paired cruciate-retaining and cruciate-substituting total knee arthroplasties (TKAs) were evaluated two to five years after surgery. In general, the more deformed knees received the cruciate-substituting prosthesis. Preoperative Hospital for Special Surgery knee scores averaged 56.4 (range, 44 68) in the cruciate-retaining knees and 53.3 (range, 29-69) in the cruciate substituting knees. Postoperatively, 25 patients were observed climbing stairs. All patients were scored and asked their preference of knees. Fifteen patients handled stairs normally. Five patients climbed stairs favoring the cruciate substituting knee and four the cruciate-retaining knee. One patient favored one knee ascending and the other descending. In the cruciate-substituting knees, there were 27 excellent and three good knee scores. There were 28 excellent and two good knee scores in the cruciate-retaining knees. Ten patients preferred the cruciate-retaining knee, eight preferred the cruciate-substituting knee, and 12 had no preference. In this group of patients no clinical advantage of one type of TKA over the other was observed. PMID- 1914287 TI - Arthroscopic treatment of symptomatic total knee arthroplasty. AB - This paper reports experience with arthroscopic treatment of 53 patients with symptomatic total knee replacements since October 1983. There were no postoperative complications. Eighteen patients were diagnosed with the tethered patella syndrome--a patellofemoral dysfunction manifested by painful popping, catching, grinding, and jumping of the patellar component. Three distinct types of bands were identified that prevented the patella from seating into the femoral sulcus and/or tethered the patellar laterally. Complete resolution of preoperative symptoms followed arthroscopic removal of the fibrous bands. Of the seven patients with arthrofibrosis, two patients had knee fusions, two are awaiting that procedure, and three patients maintained increased motion, although one remains symptomatic with pain. Two patients demonstrated patellar malalignment treated by arthroscopic lateral retinacular release. Of the 24 patients who had arthroscopic evaluation as a diagnostic procedure, five patients had retained foreign matter or soft tissue, two patients had traumatic hemarthroses, nine patients had undefined pain syndromes, one patient demonstrated posterior instability, four patients were infected, two patients demonstrated loose tibial components, and two experienced dissociation of the metal tibial component from its polyethylene-articulating surface. In the authors' experience, operative arthroscopy of the prosthetic knee was reliable, safe, and effective. PMID- 1914288 TI - Periprosthetic fractures of the femur after total knee arthroplasty. A literature review and treatment algorithm. AB - Supracondylar femur fractures after total knee arthroplasty can significantly alter the quality of knee arthroplasties and provide a challenging problem for the treating surgeon. A review of the literature and an approach to the treatment of these periprosthetic fractures is presented. The predisposing factors, mechanisms of injuries, and characteristics of the fractures are identified. A classification system is proposed based on a modified Neer grading system, the degree of comminution, and the location and character of the fracture. A treatment algorithm is developed and based on acceptable alignments of less than 5 mm translations, angulations less than 5 degrees-10 degrees, minimal rotation, less than 1 cm of femoral shortening, and proper tibiofemoral prosthetic joint alignment. PMID- 1914289 TI - Partial rupture of the distal biceps tendon. AB - Rupture of the distal biceps tendon is a relatively uncommon injury. Roentgenograms often demonstrate osseous changes at the radial tuberosity consistent with the degenerative tendon changes seen at the time of surgical repair. Partial rupture of the distal biceps tendon exhibits features similar to that of complete disruption, including acute antecubital pain, weakness of elbow flexion, and forearm supination, and differs only in that the biceps tendon is still palpable in teh partial rupture. The clinical presentation, surgical confirmation, and treatment of this condition seems not to have been reported previously in the literature. PMID- 1914290 TI - Osteoporosis and bone density measurement methods. AB - Recent technologic advances in bone mineral densitometry have resulted in increasingly precise and accurate methods of estimating bone mineral density. Dual-photon absorptiometry has been made obsolete by the introduction of dual energy radiography, a development that is likely to result in more widespread use of densitometry. The technique allows a reproducible, low dose examination of the spine, hip, and total body. Although capable of selectively measuring trabecular bone, quantitative computed tomography is currently limited to the spine, and the reliability of the technique varies from center to center. Single-photon absorptiometry and ultrasound experimental methods are of limited value because only peripheral skeletal sites can be examined by these techniques. Although invaluable in epidemiologic research and in limited clinical situations, the role of densitometry in the management and prevention of involutional osteoporosis has not been established. The evidence indicates that densitometry is unlikely to be effective as a selective screening procedure. Long-term prospective studies are needed to clarify the role of densitometry in osteoporosis management. PMID- 1914292 TI - Biomechanical study of ligaments around the elbow joint. AB - The ligamentous contribution to elbow joint stability is a product of morphology and biologic parameters of each of the collateral ligaments. Better understanding of these characteristics is of paramount importance for successful ligament reconstruction in the surgery for joint replacement and traumatic injury. Two experiments were performed. In the first, the arc of elbow flexion where the individual ligament was either taut or slack was measured; in the second, the structural properties of each collateral ligament were determined by using bone ligament-bone preparations. The anterior medial collateral ligament (AMCL) and radial collateral ligament (RCL) were taut throughout most of the entire arc of flexion. The posterior medial collateral ligament (PMCL) was taut only when the elbow was in a flexed position. Among the collateral ligaments, the AMCL was the strongest and stiffest with an average failure load of 260 N. The palmaris longus tendon, the most frequently used graft for elbow ligament reconstruction, was similar in strength (357 N). PMID- 1914293 TI - Duplex scanning versus venography as a screening examination in total hip arthroplasty patients. AB - Combined B-mode/Doppler (duplex) scanning and venography were compared in routine perioperative screening for proximal deep vein thrombosis (DVT) in 158 total hip arthroplasty (THA) patients. Preoperative scans were performed in the first 60 patients; the low preoperative prevalence of 2% for proximal DVT was thought not to warrant routine preoperative scanning. Postoperatively, duplex scanning had a sensitivity of 79%, a specificity of 98%, and an accuracy of 97% when venography was considered as the gold standard. The postoperative incidence of proximal DVT was 12% in this group of THA patients treated with mechanical and pharmacologic prophylaxis. Including calf vein thrombosis, 30% had DVT postoperatively. This study demonstrates the efficacy of duplex scanning for diagnosing proximal DVT and describes an effective noninvasive method of screening THA patients for the presence of proximal DVT. PMID- 1914291 TI - Echinococcal infestation of the spine in North America. AB - Taenia echinococcal infestation, a parasitic disease rarely seen in the United States, occurred in a 62-year-old man. Bone is involved in about 1% of all cases, and of these cases, the spine is involved in about 50%. Preoperative identification is difficult because of lack of characteristic radiographic features. Successful management is also problematic because of the difficulty of preoperative diagnosis, the invasive nature of the bony involvement, and the variable anaphylactic reaction to the cyst fluid antigen. The diagnosis must be entertained in the differential diagnosis of benign spinal neoplasms especially when dealing with patients from endemic areas. PMID- 1914294 TI - Transient osteoporosis of the hip. Magnetic resonance imaging. AB - Magnetic resonance (MR) images of seven hips were reviewed in six patients with transient osteoporosis of the hip. The MR images of the affected joint showed increased joint fluid and diffuse signal abnormalities in the marrow of the femoral head, corresponding to a decreased signal intensity on T1-weighted images and an increased signal intensity on T2-weighted images. The MR images at the time of clinical improvement showed regression of the abnormalities. These MR abnormalities reflect the pathophysiology of this condition. PMID- 1914295 TI - Femoral neck fractures. 121 cases treated by Knowles pinning. AB - The femoral neck fracture remains one of the unsolved fractures. It is a fracture with a high incidence of nonunion and avascular necrosis. One hundred twenty-one mostly young adult patients with femoral neck fractures were treated by Knowles pins internal fixation. Patients were observed for an average of 32 months following surgery. Union occurred in all Garden Stage I and II undisplaced fractures, and the incidence of nonunion was 14% in Garden Stage III and IV displaced fractures. The incidence of avascular necrosis was 5.9% in undisplaced fractures and 34.5% in displaced fractures. There was no significant difference in avascular necrosis rates among age groups. Nonunion and avascular necrosis occurred mainly in displaced fractures. Knowles pinning offers the advantages of few technical failures, early weight bearing, high union rate, and low complication rate. PMID- 1914296 TI - Comparison of porous-threaded and smooth-threaded acetabular components of identical design. Two- to four-year results. AB - Between April 1985 and April 1987, 82 smooth-threaded and 62 porous-threaded acetabular components of identical design were implanted without structural bone grafting as primary acetabular replacements. At a minimum two year follow-up examination, statistically significant differences were found in the roentgenographic and clinical results between the two matched groups. Twenty-nine percent of the smooth-threaded cups and none of the porous-threaded acetabular components were classified as roentgenographically unstable. Clinically, groin or buttock pain was present in 25% of patients with smooth-threaded cups and in only 7.5% of the patients with the porous-threaded components. Six smooth-threaded components and none of the porous-threaded components have been revised to date. Because of the unacceptable high incidence of instability at short-term follow up, the smooth-threaded acetabular component is no longer being used at this institution. The addition of the porous coating was associated with the superior results noted in this group. PMID- 1914297 TI - Osteochondritis dissecans of the patella. MRI evaluation and a case report. AB - Osteochondritis dissecans of the patella is a rare cause of anterior knee pain. An illustrative case in a 22-year-old man demonstrates the current imaging modalities and surgical treatment. Specifically, magnetic resonance imaging (MRI) and arthroscopic knee surgery are discussed along with a review of the literature. Unlike standard roentgenograms, MRI can be helpful in determining the viability of the osteochondritic fragment and the amount of remaining attachment to the surrounding cancellous bone. This finding can have important bearing on choice of treatment. When surgery is indicated, arthroscopic treatment with excision of the fragment and curettage offers distinct advantages over open arthrotomy. Lateral release or other realignment procedures may be done in combination with the primary procedure. Prognosis for full recovery of knee function and relief of patellar pain is guarded in patients who require surgery. PMID- 1914298 TI - The effect of patient age, gender, and tibial component fixation on pain relief after cementless total knee arthroplasty. AB - Cementless total knee arthroplasties (TKAs) were prospectively evaluated for pain relief in 1110 knees. The effect of screws in the tibial component, the age of the patients, and the gender of the patients were studied to determine the effect of these parameters on pain relief one and two years postsurgery. The group with screws in the tibial component (Ortholoc II) had a significantly higher percentage of pain-free knees at one year than at two years postsurgery, and the older patients had a significantly higher rate of pain-free knees at one- and two years postsurgery than the younger patients. Older female patients with Ortholoc I TKAs had a significantly higher percentage of pain-free knees than did older male patients at one-year postsurgery, but not at two years. The group with screws in the tibial components (Ortholoc II) had a higher percentage of pain free knees at one-year postsurgery than did the Ortholoc I knees, but there was no difference between Ortholoc I and II at two-years postsurgery. In the Ortholoc II group, there was also no difference in results among sexes or between patients older and younger than 65 years old. The correlation coefficient was calculated to evaluate the relationship between body weight and the degree of pain after TKA. No significant correlation could be found at one and two years after surgery. PMID- 1914299 TI - High tibial osteotomy. Use of an osteotomy jig, rigid fixation, and early motion versus conventional surgical technique and cast immobilization. AB - High tibial osteotomy (HTO) using conventional surgical technique and cast immobilization was compared to HTO using an osteotomy jig, rigid internal fixation, and early motion. Fifteen patients (19 knees) had conventional HTO. The mean preoperative femoral-tibial angle was 2.5 degrees of varus, and the mean postoperative angle was 6.5 degrees of valgus. Two knees were undercorrected and eight knees (42%) had associated complications. Twenty patients (21 knees) had HTO utilizing the new surgical technique and postoperative management. The mean preoperative femoral-tibial angle was 2.3 degrees varus, and the mean postoperative angle was 7.6 degrees valgus. One knee was undercorrected (less than 4 degrees valgus) and one knee (5%) had an intraoperative intraarticular fracture. High tibial osteotomy with an osteotomy jig to provide accurate correction, and rigid internal fixation to allow early motion, is an attractive alternative to conventional HTO. PMID- 1914300 TI - Localized pigmented villonodular synovitis of the knee. Arthroscopic treatment. AB - Localized pigmented villonodular synovitis is a lesion that may affect any joint but is frequently found in the knee. Because of its rarity, diagnostic omissions are common. Definitive treatment usually involves resection of the lesions as well as a synovectomy. Nine patients were treated arthroscopically, thereby avoiding arthrotomy. There was no evidence of recurrence at the follow-up evaluation (range, 25-108 months; mean, 48 months). The patients with mechanical knee symptoms had small nodular lesions anteriorly related to the menisci; those with degenerative symptoms had slightly more prolific nodules in other sites. No recurrence occurred in either group. PMID- 1914301 TI - Use of carbon fibers in the reconstruction of knee ligaments. AB - Carbon fibers were used to reconstruct the anterior cruciate ligament and other knee ligaments in a consecutive series of 26 (mostly acute) patients who had suffered serious occupation-related injuries. After an average follow-up time of 52.4 months (one patient lost, one patient refused follow-up examination), the anterior drawer at 30 degrees was less than 5 mm (side-to-side difference) in 14 patients, 5-10 mm in six patients, and greater than 10 mm in four patients. Of 24 evaluatable patients, 22 returned to work, including 20 patients who work underground. Chronic pain, recurrent effusion, infection, and tender nodes did not occur in the series. Arthroscopic examination of five patients revealed minimal intraarticular debris. PMID- 1914302 TI - Functional hallux rigidus in the rheumatoid foot. AB - Hallux rigidus results from arthritic involvement of the first metatarsophalangeal joint. The authors have observed loss of motion at this joint in patients with rheumatoid arthritis in the absence of hallux valgus or joint destruction. A hyperextension deformity of the interphalangeal joint has also been observed, with a painful callus beneath it. The first metatarsophalangeal joint appears normal on roentgenograms, and passive motion of the joint is normal when it is examined clinically. The loss of first metatarsophalangeal motion is functional, and stems from muscle spasm of the great toe intrinsic muscles in an effort to relieve pressure on the lesser metatarsal heads. The interphalangeal hyperextension may develop secondary to "functional hallux rigidus." PMID- 1914303 TI - Shoulder strength analysis using the Cybex II isokinetic dynamometer. AB - The purpose of this study was to establish a data base of normal shoulder strength of young adults using the Cybex II dynamometer and specially designed fixation devices. Fifty healthy subjects aged 21 to 40 years old (26 men, 24 women) were tested. The mean peak torque values of their shoulders were measured at speeds of 0 degree, 60 degrees, 180 degrees, and 300 degrees per second. Mean peak torque values generally decreased as speed increased. Men were significantly stronger than women for all motions and speeds tested. Shoulder extension torque was greatest followed by adduction, flexion, internal rotation, abduction, and external rotation. Torque production tended to be greater on the dominant side. PMID- 1914304 TI - Fracture through the stalk of pedunculated osteochondromas. A report of three cases. AB - Although fracture through the base of an osteochondroma is a well-recognized clinical entity, the fate of such fractures has never been documented. Recommendations concerning the treatment of these fractures are contradictory. Of the three cases of fracture through the base of a pedunculated osteochondroma observed in the last 12 years, two healed without problem, one in a patient with a solitary osteochondroma, the other in a patient with multiple osteochondromas. The third patient remained symptomatic one year after injury, and histologic evaluation of the specimen after surgical excision confirmed the diagnosis of fibrous nonunion of the fracture. Experience with fractures through the base of a pedunculated osteochondroma suggests that the majority of these fractures will heal without complication, regardless of whether they involve solitary or multiple osteochondromas. However, symptomatic fibrous nonunion of such a fracture may occur particularly when an osteochondroma is located near large, mobile tendons. PMID- 1914305 TI - Fractures following limb-salvage surgery and adjuvant irradiation for soft-tissue sarcoma. AB - In a prospective study, consecutive patients were treated for soft-tissue sarcoma (STS) by wide resection and adjuvant irradiation. Twelve patients had resection of bone to achieve a tumor free margin; five of these patients were left with lower extremity open segmental cortical defects in the high-dose radiation field. Four of the five patients with cortical defects suffered a fracture through the defect more than six months after surgery. Only one of 71 patients not treated with bony resection suffered a late fracture. Patients requiring bony cortex resection for STS of the lower extremity should be considered at risk for late fracture if adjuvant irradiation is prescribed. PMID- 1914306 TI - The histomorphologic and morphometric study of asymptomatic hip arthroplasty. A postmortem study. AB - The purpose of this study was to determine the histologic findings at the bone cement interface in successful asymptomatic total hip replacements (THR) retrieved from patients at autopsy. The criteria for a successful hip arthroplasty were clinical, radiologic, and direct examination of the prosthesis at the time of harvesting. Twelve patients with a total of 14 cemented hip arthroplasties came to autopsy at a mean of 4.7 years after implantation. A detailed histomorphometric objective means of assessing the tissue response was applied to the membrane. The density of histiocytes correlated with the thickness of the membrane, the density of polyethylene particles, and the time after implantation. The fibrohistiocytic membrane in this group of patients was similar to that described in the literature in cases of loose THRs. These findings advance current understanding of transcellular particle transportation (directional exocytosis) in tissue reactions to endoprostheses of THR. PMID- 1914307 TI - Cementless total knee arthroplasty in patients over 65 years old. AB - Many factors influence the decision to implant a knee prosthesis with or without cement. Implant retrieval studies have demonstrated that bone ingrowth into porous-coated devices is possible even in older age groups. Early clinical follow up observations suggest that cementless total knee arthroplasty can be successful in patients over 65 years of age, and need not be reserved for younger patients. PMID- 1914308 TI - Zonal and age-related difference in the amounts of creatine kinase subunits in cartilage. AB - Energy metabolism in cartilage may affect the morphogenetic events of skeletal growth. Investigating enzymes responsible for energy metabolism in cartilage, such as creatine kinase (CK), can provide clues to an understanding of pathogenesis and treatment of osteochondrodysplasias. In this study levels of CK subunits M (muscle type) and B (brain type) were measured by a highly sensitive enzyme immunoassay system in growth and resting cartilages of the rat rib at various ages. CK-M was predominant, but there was no statistically significant difference in its quantity of CK among cartilages of various ages or between resting and growth cartilage. In contrast, although CK-B levels were low, they showed a significant decrease with advancing age and a significant increase in growth cartilage as compared with resting cartilage. The results of this study suggest that CK in cartilage, especially CK-B, may play an important role in skeletal growth. PMID- 1914310 TI - Electron microscopic analysis of the interdigital neuroma. AB - Electron microscopic evaluation was investigated in surgical specimens of interdigital neuroma. Edema of the endoneureum, fibrosis beneath the perineurium, axonal degeneration and necrosis suggest nerve damage occurs secondary to mechanical impingement in the etiology of interdigital neuroma. PMID- 1914309 TI - Arachidonic acid metabolism in articular chondrocytes. AB - In this study rabbit articular chondrocytes were cultured and the cells were labeled with 3H-arachidonic acid and 14C-stearic acid. 3H incorporation reached a plateau at four hours and 14C-incorporation reached a plateau at 24 hours. The 3H was associated mainly with phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) at the 2-position while 14C was found at the 1-position. When the double-labeled cells were incubated with bradykinin or ionophore A23187, a significant release of 3H into the medium was observed, while the 14C release was small. Approximately 90% of the 3H released was arachidonic acid. Small amounts of the released 3H were no longer associated with stearic acid; it was converted mainly into prostaglandin E2 (PGE2). When stimulated by either bradykinin or ionophore, a significant 3H loss was observed in cellular PC while there were no significant 3H changes in other phospholipids, triacylglycerols (TGs), or diacylglycerols (DGs). Although 14C of cellular lysophosphatidylcholine (lyso-PC) was not increased significantly, the 3H seemed to be released from the 2-position of PC by the action of phospholipase A2. There was no significant change in the breakdown of PC between palmitoyl-arachidonyl (16:0/20:4) and stearoyl-arachidonyl (18:0/20:4) species. Both A23187 and bradykinin may activate phospholipase A2, releasing arachidonic acid equally from the 2-position of PCs having either palmitic acid or stearic acid at the 1 position. Some of this material is converted to PGE2, but this conversion is low compared to other cell types. PMID- 1914311 TI - Surgical treatment of fresh injuries to the major ligaments of the knee. 1950. PMID- 1914312 TI - Suppression of prostaglandin E2 synthesis in the membrane surrounding particulate polymethylmethacrylate in the rabbit tibia. AB - Fifteen mature, New Zealand, female rabbits were divided into two groups. Using sterile technique, a 6-mm drill hole was made in the tibia 1 cm distal to the knee joint bilaterally. The marrow was scooped out underneath the hole. The right tibia received Simplex particulate cement polymer and the left leg functioned as a prepared, but nonimplanted, control. All animals were fed a standard diet. Whereas the six animals in Group 1 received regular water, the nine animals in Group 2 drank water in which sodium naproxen was dissolved (1.375 mg per ml). The animals were killed after 16 weeks. The implant area was harvested under sterile conditions and maintained in tissue culture. The cumulative collection of tissue culture supernatants over a three-day period was assayed for Prostaglandin E2 (PGE2) via radioimmunoassay. Specimens from Group 1 produced an average of 106.0 +/- 10.9 ng PGE2 on the right side, and 35.3 +/- 6.0 ng PGE2 on the left side. Specimens from Group 2 produced an average of 31.1 +/- 6.1 ng PGE2 on the right experimental side and 26.0 +/- 5.1 ng PGE2 on the left control side. The ratio of PGE2 values for the right divided by the left side yielded higher values in Group 1, compared to Group 2. Cement polymer particles have been shown to produce a florid foreign body histologic reaction similar to that associated with prosthetic loosening in man. This experiment has demonstrated that the increased PGE2 production by the membrane surrounding particulate cement polymer can be suppressed by the administration of an oral cyclo-oxygenase inhibitor. PGE2 has been previously shown to induce bone resorption in vivo and in vitro. The use of nonsteroidal antiinflammatory drugs may be indicated in retarding the bone loss associated with early prosthetic loosening. PMID- 1914313 TI - The effect of extraarticular varus and valgus deformity on total knee arthroplasty. AB - Because of trauma, metabolic bone disease, congenital deformity, or prior osteotomy, an extraarticular deformity may be present in patients requiring total knee arthroplasty. If the extraarticular deformity is not corrected extraarticularly, it must be corrected by compensatory distal femoral or proximal tibial wedge resection to produce overall limb alignment. Because such a wedge resection between the proximal and distal attachments of the collateral ligaments will produce asymmetrical ligament length, complex instabilities may result. This article, through overlay templates and trigonometric analysis, evaluates all the issues confronting the surgeon deciding whether to pursue intraarticular or extraarticular correction. The conclusions are as follows: (1) the closer a deformity is to the knee, the greater its importance, (2) femoral deformities are more difficult to correct intraarticularly than tibial deformities because femoral compensatory wedge resection produces instability only in extension, and (3) intraarticular correction of varus deformities produces lateral instability that is usually better tolerated than medial instability, and some extraarticular deformities are best treated by extraarticular correct, independent, or total knee arthroplasty. PMID- 1914314 TI - The lateral approach to the valgus knee. Surgical technique and analysis of 53 cases with over two-year follow-up evaluation. AB - Valgus deformity correction poses a major challenge in total knee arthroplasty (TKA). The standard medial approach has many technical limitations and disadvantages that include patellofemoral maltracking and subsequent patellar problems. The lateral approach has been developed and utilized successfully in 79 cases (53 with over two-year follow-up evaluation) since 1980. The biomedical rationale of the approach is sound, and addresses the pathologic anatomy of fixed valgus deformity. Surgical technique is direct, anatomical, more physiologic, and maintains soft-tissue integrity. The "lateral release" is performed as part of the approach. Patellofemoral tracking and alignment stability are optimized and medial blood supply preserved. Clinical experience has shown the approach to be more aesthetic and results objectively superior. Scores have been good/excellent in 94.3% of cases. Knee stability is enhanced with the use of nonconstrained prostheses in this difficult group of patients. The lateral approach is recommended as the "approach of choice" for fixed valgus deformity in TKA. PMID- 1914315 TI - Bone deficiency in total knee arthroplasty. Use of metal wedge augmentation. AB - Twenty-eight knees in 25 patients with a metal wedge augmentation for tibial bone deficiency were reviewed at 2.3 +/- 0.6 years (range, 2-3.5) after surgery. A medial side wedge was used in 24 knees and a lateral side wedge in four. The preoperative bone defect size was 12 mm +/- 6 mm on the medial side and 8 mm +/- 2 mm on the lateral side. The knee scores improved from a preoperative mean of 53 +/- 12 to 89 +/- 8 at the last evaluation. There were 79% excellent and 21% good results. There were no complications or reoperations. Radiolucent lines beneath the metal wedge were present in 13 knees but none were progressive. PMID- 1914316 TI - Patellar tendon bone grafting for patellectomized patients having total knee arthroplasty. AB - A technique for restoring the moment arm to improve quadriceps leverage after patellectomy has been developed and used in patients treated with total knee arthroplasty. Essentials of the technique involve use of a 2.5-cm diameter by 1 cm thick bone graft sewn into the previous anatomical position of the patella, using a subsynovial pouch for stabilization. Clinically, seven knees in six patients were treated with patellar tendon bone grafting during total knee arthroplasty. The final outcome of these patients was evaluated from 24 to 125 months (mean, 75.4 months). Good to excellent results were demonstrated in six of seven knees (85.7%) with sufficient extension power for normal gait in most cases. Failure to achieve painless, active extension was seen in one patient following revision knee arthroplasty complicated by chronic reflex sympathetic dystrophy of the knee. Patellar tendon bone grafting improves quadriceps leverage in previously patellectomized knees and is useful in restoring extensor function in such patients having primary or revision knee arthroplasty. PMID- 1914317 TI - Universal intramedullary instrumentation for unicompartmental total knee arthroplasty. AB - Certainly the advantages of unicompartmental total knee arthroplasty (TKA) are appealing as opposed to tricompartmental arthroplasty. Patients who have had unicompartmental arthroplasty have significant preservation of existing bone stock. They have an improved range of motion and they are definitely easier to revise. This reduces hospitalization time as well as costs with retention of more normal anatomy. In patients with unicompartmental disease with minimal patellofemoral changes, clinical results are certainly encouraging in terms of patient satisfaction with unicompartmental arthroplasty as opposed to tricompartmental arthroplasty. Restoration of function is unquestionably closer to normal than with tricompartmental arthroplasty. The advantages of an intramedullary instrumentation system for unicompartmental disease allows for a more standard method of placing unicompartmental prosthetic components so that less "eyeballing" occurs. Furthermore, utilization of a system that allows for more precise anatomical cuts should allow for better component fit as well as a return to a more normal femoral-tibial angle. PMID- 1914318 TI - The long-term efficacy of unicompartmental arthroplasty of the knee. AB - In a retrospective study of 48 consecutive patients (63 knees) treated by a medial unicompartmental arthroplasty for degenerative arthritis, all of the operations were performed by a single surgeon. Only Compartmental II femoral prostheses were used, coupled with either a Robert Brigham or Compartmental II tibial prosthesis that was greater than 6 mm in thickness. All components were cemented. Forty-four knees were available for follow-up examination that was performed five to 12 years postoperatively (mean, 7.4 years) by one examiner. There were 43 satisfactory results (89.6% of knees), one fair (2.1%), and four revisions (8.3%). Two knees (4.5%) had roentgenographic evidence of disease progression. Valgus alignment did not appear necessary for a satisfactory result, although most knees were within 4 degrees of neutral. Unicompartmental knee arthroplasty is indicated in properly selected patients. When properly performed, this procedure should last longer than five years. PMID- 1914319 TI - Contamination of operating room personnel during total arthroplasty. AB - The authors prospectively evaluated the degree of contamination to the operating room team during 60 consecutive total joint arthroplasties. Each member of the team was required to wear a hood, mask, protective eyewear, and shoecovers. At the conclusion of each procedure, all members were assessed in terms of degree and location of contamination. One hundred percent of the surgeons and first assistants were exposed. The face and eyewear were noted to be the area of greatest contamination. The authors found orthopedic surgeons to be at significant risk of contamination with blood and body fluids during total joint arthroplasty. PMID- 1914320 TI - Unicompartmental knee arthroplasty. Eight- to 12-year follow-up evaluation with survivorship analysis. AB - One hundred consecutive unicondylar knee arthroplasties were reviewed after eight to 12 years of follow-up evaluation. Eighteen patients (19 knees) had died, four patients (four knees) were lost to follow-up evaluation, and 13 patients (13 knees) had revision. Survivorship analysis revealed 90% survivorship of the prostheses at nine years, 85% at ten years, and 82% at 11 years. Sixty-four knees in 51 patients were studied clinically and roentgenographically at final follow up study. Of these, 87% had no significant pain. The average knee flexion was 115 degrees. Anatomic knee alignment averaged 3 degrees of valgus for the knees with preoperative varus alignment and 8 degrees of valgus for knees with preoperative valgus alignment. Fifteen percent of these elderly patients (mean age, 80 years) used a cane outdoors, but only 8% because of their knee. Sixty percent had radiolucent lines at the tibial bone-cement interface, and these lines were incomplete in 96% of cases. PMID- 1914321 TI - [The relationship between P300 latency and regional cerebral blood flow in patients with cerebral infarction in the territory of the deep perforators]. AB - We studied the relationship between P300 latency and regional cerebral blood flow (rCBF) in nondemented patients with cerebral infarction. Subjects were 24 nondemented patients (mean age 64.1 years) who had a CT-proven infarct in the territory of the deep perforators of the internal carotid artery system and 53 controls (mean age 64.1 years). Prolongation of P300 latency with advancing age was observed in the both groups. There was no significant difference in P300 latency and rCBF between the two groups. There was a negative correlation between P300 latency and rCBF, especially in the bilateral fronto-parietal regions in the patient group. These results indicate that cognitive function assessed by P300 latency may be related to rCBF in the fronto-parietal region in the nondemented patients with lacunar infarctions. PMID- 1914322 TI - [Autosomal recessive oculopharyngeal "muscular dystrophy"--clinical features and association with reduced activity of myophosphorylase]. AB - We reported two cases of brothers demonstrating oculopharyngeal muscular dystrophy (OPMD). The cases had consanguineous parents and five healthy siblings, which suggested the autosomal recessive inheritance. The initial symptom was slowly progressive blepharoptosis with onset in the third decade. On examination, total external ophthalmoplegia was observed in both patients. Additionally, the elder, a 57-year-old man, exhibited dysarthria, dysphagia and muscular weakness with atrophy of the face, bilateral proximal upper limbs and diffuse lower limbs. The younger brother, a 55-year-old man, displayed muscular weakness and atrophy distributed in the face and four limbs. Muscle biopsy of both cases revealed rimmed vacuoles and spheroid bodies in the atrophic and normal-sized fibers. Biochemical study of the biopsy specimens of the elder brother disclosed the myophosphorylase activity reduced to about 40% of the normal value, although in the younger brother, that activity was normal. OPMD is usually inherited in the autosomal dominant mode, and autosomal recessive OPMD is rare. The onset age of our cases was younger than that of the autosomal dominant OPMD. There were some differences in the clinical manifestation between the presented cases, which could be interpreted as phenotypic variation. The elder brother was thought to be associated with McArdle's disease. PMID- 1914323 TI - [Anticardiolipin antibody in cerebral infarction]. AB - We investigated the anticardiolipin antibody (ACA) in a series of patients with cerebral infarction without systemic lupus erythematosus (SLA). Clinical and laboratory data were assessed from a series of 250 non-SLE patients with cerebral infarction who visited our clinic from 1988 to 1990. The concentration of anticardiolipin IgG antibody was measured by an enzyme-linked immunosorbent assay technique. An elevated ACA level was defined as one which was greater than 3 standard deviations above the mean level for normal controls. We examined the CT findings and risk factors for stroke such as hypertension, diabetes mellitus, hyperlipidemia and cardiac disease. Laboratory data such as the platelet count, the presence of lupus anticoagulant and a biologic false-positive test for syphilis were also investigated. Among the 250 patients with infarction, IgG ACA was detected in 22 (8.8%). There was no significant difference in incidence of ACA between the patients with cerebral thrombosis and those with cerebral embolism. On CT scan, multiple cerebral infarcts were noted in 18 of the 22 patients. As regards the location of the infarct, the cerebral cortex together with the basal ganglia was more common than isolated lesions of the cortex or basal ganglia. Concerning the risk factors for stroke, hypertension was noted in 12, diabetes mellitus in 2, hyperlipidemia in 2 and cardiac disease in 2. Lupus anticoagulant and thrombocytopenia were not detected in any of the cases. A biologic false-positive test for syphilis was observed in one case. Dementia was present in 12 of the 22 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914324 TI - [Pathogenesis of ipsilateral hemiparesis in patients with lateral medullary syndrome]. AB - Lateral medullary syndrome is known to cause hemiparesis ipsilateral to the medullary lesion. However, it's clinical significance has not been fully evaluated. In this study, we made clinical and angiographic studies in patients with syndrome to elucidate the pathogenesis of ipsilateral hemiparesis. Thirty four patients with cerebral infarction presenting with this syndrome were studied. Their mean age was 51 years and all the patients were examined within 6 months of their first attack. Diagnosis of ipsilateral hemiparesis was made if subjective feeling of weakness in the upper and lower extremities was associated with increased deep tendon reflexes. Ipsilateral hemiparesis was observed in 38% of all the patients. Cerebral angiography was performed in 26 patients and divided into two groups; group A with ipsilateral hemiparesis (n = 9) and group B without ipsilateral hemiparesis (n = 7). In 56% of patients in group A, angiography showed non-visualization of ipsilateral vertebral artery (VA) and posterior inferior cerebellar artery (PICA). Non-visualization of these two arteries never occurred in the patients of group B. On the other hand, non visualization of VA alone was observed in 35% of the patients in group B, but it was none in the patients of group A. However, there were no differences in concerning the frequency of non-visualization of PICA alone or non-occlusion at all between both groups. Therefore, the focal ischemia in the region below the pyramidal decussation due to the occlusion of both VA and PICA, regardless of thrombotic or embolic episode, was considered to be responsible for ipsilateral hemiparesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914325 TI - [Hypothyroidism with increased serum levels of cholestanol and bile alcohol- analogous symptoms to cerebrotendinous xanthomatosis]. AB - We reported a 53-year-old woman with hypothyroidism due to ectopic thyroid gland. She showed intellectual impairment, bilateral pyramidal tract sings, slight cerebellar signs, and degenerative changes of brain white matter on CT and MRI, which were similar to symptoms and signs in cerebrotendinous xanthomatosis (CTX). We found increases of serum cholestanol in the patient and additional 3 patients with hypothyroidism. Total bile alcohol was also increased in the serum of the patients. We speculate that hypothyroidism and CTX might have a similar pathophysiological background on the development of neurological complications and atherosclerosis. PMID- 1914326 TI - [Adverse effects of branched chain amino acid transfusion on type-II citrullinemia--report of an adult case]. AB - A 24-year-old man was admitted to our hospital, because two days before the admission he had abruptly lost consciousness following generalized convulsive seizures. He had a past history of transient amnesia and a favor for peanuts. His grandparents had a record of consanguinity. On admission, he was comatose and flaccid with his four extremities. Laboratory examination revealed the followings; mild degree of abnormal liver function, slight elevation of blood ammonia, irregular theta basic rhythm on EEG, marked brain edema on CT and a normal liver ultrasonography. From the second hospital day, in addition to antiepileptic drugs and adrenocorticosteroids, branched chain amino acid was administered to reactivate damaged brain functions. Thereafter, the concentration of blood ammonia increased to more than 3,000 micrograms/dl, and as a result he fell into status epilepticus. On the fourth hospital day, the levels of citrulline in the plasma and urine taken on the first hospital day were found to have increased by 20 and 100 times, respectively. Although the transfusion of branched chain amino acid was stopped, he died while in coma on the 12th hospital day. Enzymatic analyses of necropsied liver specimens revealed that the quantitative activity of argininosuccinate synthetase had decreased to less than 10% in his urea cycle. In this patient, it was noted that, after transfusion of branched chain amino acid, his brain activities turned worse and blood ammonia was markedly elevated. There is a possibility that intravenous administration of branched chain amino acid may interrupt the urea cycle balance in an adult patient of citrullinemia with dysfunction of the brain, kidney and muscle, especially with brain edema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914327 TI - [A family of Machado-Joseph disease with a patient having frequent apnea in all day]. AB - One male and two female cases in a family of Machado-Joseph disease were reported. Two cases showed typical symptoms that are characterized by bulging eyes, ophthalmoplegia, dystonia, ataxia, spasticity of extremities and amyotrophy, and were consistent with Type II (Rosenberg et al). But another one lacked diversity of the symptoms, showing mainly progressive cerebellar ataxia for over 10 years. We pointed out the existence of a new type of MJD case exhibiting only progressive cerebellar ataxia over a long period. A female patient had dyspnea and insomnia after 20 years in her clinical course, and central sleep apnea was revealed by respiratory monitor. But, the apnea and irregular respiration appeared in both awake and sleep stages. We described the importance of attention to the apnea as a new complication of Machado-Joseph disease. PMID- 1914328 TI - [A case of scapuloperoneal atrophy with rigid spine having lobulated fibers in muscle biopsy]. AB - The patient, a 52-year-old male, noticed abnormalities on walking at about 20 years of age, followed by slowly progressive muscle weakness of arms and neck. The family history was negative. He showed muscular atrophy and weakness with a preferential involvement of the scapular, arms and peroneal muscles. Deep tendon reflexes were absent. He had a limited range of motion in the spine, but the onset was unclear. Creatine kinase (CK) was elevated (324 IU/L) and the EMG study showed myogenic pattern. Muscle biopsy was obtained from the biceps brachii muscle; on NADH dehydrogenase stain, there was subsarcolemmal increase in the oxidative enzyme activity showing "lobulated fiber" mostly seen in type 1 fibers. On electron-microscopy, the sub-sarcoplasmic areas which had high NADH activity, contained many mitochondria and glycogen particles. However, iodine-glycogen complex spectrum analysis pattern and debranching enzyme activity were normal. CT scan revealed low density in the paravertebral muscles, suggesting degeneration. This is a rare type of scapuloperoneal atrophy different from Emery-Dreifuss syndrome, rigid spine syndrome and FSH type muscular dystrophy. PMID- 1914329 TI - [A case of postinfectious polyradiculoneuropathy initially manifested as sudden and severe bilateral hearing loss]. AB - A 48-year-old man noted epi-gastralgia, right back pain and lumbago. One week later he developed sudden and severe bilateral hearing loss and progressive difficulty in walking due to generalized muscle weakness of the four extremities. In AIDP, involvement of the 8th cranial nerve is very rare. At the initial stage of the illness ABR disclosed prolonged latency of wave V, and other waves were not detected at all. Thereafter the ABR findings improved gradually with concomitant improvement of the clinical signs and symptoms, and waves I and III became identifiable together with a shortening of the latency of wave I. These ABR findings suggest that the main lesion in this patient involves the peripheral part of the cochlear nerve. Antibody titers for HSV-I were high in CSF and serum at the initial stage, and decreased gradually in parallel with the improvement of the neurological signs and symptoms. Seven cases of AIDP or Guillain-Barre syndrome with impairment of the 8th cranial nerve have been reported in the literature. Nevertheless, the present case is of interest because of the severity of the hearing impairment and also because this is the first case for which the time courses of ABR findings and HSV-I antibody titers are available. PMID- 1914331 TI - [Perifascicular necrosis and regeneration in a case of adult polymyositis]. AB - We report a case of adult polymyositis with peculiar muscular pathology of innumerable muscle fiber necrosis and regeneration accentuated in the perifascicular area. A 51-year-old woman developed generalized weakness of the extremities, trunk and bulbar muscles subacutely for two months. Anterior tibial muscle biopsy showed numerous tube-like necrotic/regenerative muscle fibers predominantly in the perifascicular area. The diameters of the muscle fibers were smaller in the periphery of the fascicles. Small arteries at the center of the fascicles occasionally showed marked perivascular cuffing, although complement component C9 was negative in the vessel wall. The gradient of the diameters of necrosis/regeneration fibers was thought to have been caused by ischemia of the muscles, which persisted at the perifascicular area leading to recurrent necrosis and regeneration and gradually invaded towards the center of the fascicles. We designated this muscular pathology as perifascicular necrosis and regeneration, and regarded it was an acute severe form of the perifascicular ischemic lesions of myositis. PMID- 1914330 TI - [Congenital facioscapulohumeral muscular dystrophy associated with tongue atrophy and sensorineural hearing disturbance]. AB - An 18-year-old high-school boy presented facial muscle weakness since birth, and then developed wasting around the neck, shoulder girdle, upper arms, and thighs. He was born to un-consanguineous parents. His father had suffered from similar but milder muscle atrophy with predominance on the right side of the face and shoulder girdle since adolescence. His mother and his only sibling were clinically unaffected. Hearing disturbance was detected at the age of 6, and he also noted atrophy of the tongue and the bilateral thighs at the age of 10. The symptom progressed gradually. Neurological examination on admission revealed a well-developed boy (166 cm/60 kg) with a prominent facial diplegia with distinct proximal muscular atrophy of the extremities. Muscles of the tongue, neck, upper arms, shoulder and pelvic girdles, and hamstrings were markedly involved. The anterior tibial muscles were also affected, while the calf muscles were hypertrophic. High arched palate, X legs, mild lordoscoliosis were also noted. Serum CK was slightly increased (424 IU/l), and needle EMG in the extremities including the tongue revealed myopathic changes. Muscle CT demonstrated marked atrophy of the proximal muscles in the lower limbs and hypertrophy of the calf muscles. Audiogram showed bilateral sensorineural hearing disturbance. Muscle biopsy of the gastrocnemius showed myogenic as well as neurogenic changes consisting of atrophic and hypertrophic fibers with interstitial cellular infiltration, and type I fiber predominance. With these family history as well as clinical and laboratory examinations, this case could be diagnosed as "congenital facioscapulohumeral muscular dystrophy".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914332 TI - [A case of subacute idiopathic pure pan-dysautonomia--recovery with prednisolone therapy]. AB - A 52-year-old man had, after an episode of fever in June 1989, developed orthostatic dizziness followed by sexual impotence, dysuria, decreased sweating and weight-loss, which progressed gradually and reached their maximum seven months after the onset. He was given 400 mg of droxydopa and 8 mg of midodrine HCL per day without apparent benefits, and was admitted to our hospital. His blood pressure (mmHg) and heart rate were 167/102 and 68 in supine position, and 74/41 and 62 in sitting position. Skin was dry. Pupillary reactions were sluggish. Left pupil was slightly irregular. Other cranial nerves, sensory and somatic motor functions were normal. Laboratory tests revealed as follows: slight anemia, ESR 42 mm/hour, serum IgG 2236 mg/dl, CSF protein 64 mg/dl and positive tests for non-specific autoantibodies. Nerve conduction studies and electromyogram were normal. Autonomic function tests showed postganglionic impairments of sympathetic and parasympathetic systems. The sural nerve biopsy disclosed normal myelinated fibers, but decreased unmyelinated fiber density to 60% of the control value. No demyelinating lesions, cell infiltration or amyloid deposits were seen. Under the diagnosis of idiopathic pure pan-dysautonomia, prednisolone, initially 60 mg daily, was added. Within 10 days, he showed marked improvement of general conditions. No exacerbation was seen during reduction or after withdrawal of prednisolone. Repeated tests showed normalizing laboratory data and regression of autonomic deficits. A year after onset he regained normal social life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914333 TI - [A case of cerebral infarction with circulating anticoagulant to Fletcher factor]. AB - A 44-year-old woman with a history of cerebral infarction and hypertension developed sudden onset of speech and visual disturbance. On admission, her general physical examinations showed high blood pressure of 210/120 mmHg and Raynaud's phenomena. The neurological examinations revealed right upper quadratic hemianopsia, left oculomotor nerve paresis and left hyperreflexia. Laboratory findings showed that antinuclear and anti-DNA antibodies were positive. The activity of Fletcher factor was reduced to 50%, and the activated partial thromboplastin time (APTT) was prolonged to 82.6 seconds. And a 1:1 dilution with normal plasma failed to correct the prolonged APTT, indicative of circulating anticoagulant to Fletcher factor. Plasma fibrinogen increased to 500 mg/dl but FDP was normal. The CT scan demonstrated the recurrently developed cerebral infarction in the left occipital lobe. Cerebral angiogram revealed mild atherosclerosis of basilar and bilateral posterior cerebral arteries, but any occlusive lesions were not found. Although she had a history of hypertension, this case suggests the possibility that the disturbance in fibrinolytic system may have been caused by the circulating anticoagulant to Fletcher factor, and contributed to her cerebral infarctions. PMID- 1914334 TI - [A case of lobar cerebral hemorrhage with low concentration of CSF cystatin C]. AB - A 49-year-old male was admitted to our hospital because of severe headache and dizziness which had occurred suddenly one day before admission. There was no past history contributory to cerebral hemorrhage but was family history of cerebrovascular accidents in his father and brother. Neurological examination revealed left homonymous hemianopsia, mild left hemiparesis, and left side hemi neglect in simultaneous stimuli on bilateral extremities. Laboratory data including peripheral blood cells, coagulation tests, and serum chemistry were unremarkable. Brain CT and MRI demonstrated large lobar hematoma in the right parieto-occipito-temporal region. Cystatin C level in the CSF samples taken on the 39th and 59 th days (38 and 27 ng/ml respectively) were low, compared with the normal value (greater than 100 ng/ml). These findings suggest that the lobar cerebral hemorrhage of the present case might have been caused by cerebral amyloid angiopathy with cystatin C deposits. PMID- 1914335 TI - [A case of Behcet disease with transverse sinus thrombosis and successful treatment with colchicine]. AB - A 64-year-old man was admitted to our hospital because of headache and fever. Four months before admission, he had suffered from thrombophlebitis of the legs, erythema, oral aphtha and genital ulcers, and was diagnosed as having Behcet disease. Several days prior to admission he developed fever and was treated with enoxacine, which caused disorientation and abnormal behavior. These psychiatric symptoms disappeared after enoxacine was discontinued. On admission he was neurologically normal. Fever and headache disappeared spontaneously. However, he complained again of headache, and was suspected to have cerebral sinus thrombosis. Brain CT scan showed no abnormality, but brain MRI and cerebral angiography demonstrated right transverse sinus thrombosis and stasis. He was treated with colchicine, isosorbide, and ticlopidine. Because he had a gastric ulcer, corticosteroids were not indicated. Two months later, brain MRI demonstrated reduction of the size of the sinus thrombosis, and the clinical outcome was favorable. We would like to emphasize the usefulness of MRI and colchicine in the patient with Behcet disease complicated by sinus thromboses. PMID- 1914336 TI - [A case of adrenomyeloneuropathy with marked spinal cord atrophy on magnetic resonance imaging]. AB - A 29-year-old man complained of increasing paraplegia and sphincter disturbances. On admission, he was 23 years old. He had moderate pigmentation of the skin, and his neurological examinations revealed spastic paraplegia, hyperreflexia of both legs with Babinski's signs, a pinprick sensation deficit below the L-1 level, loss of vibration sense in the lower extremities and horizontal nystagmus on lateral gaze. Endocrinological examinations revealed adrenocortical insufficiency. CSF, EEG, EMG, brain-CT and myelography did not show any abnormalities, but metrizamide CT myelography at the low thoracic spinal cord revealed decreased cord diameter. Nerve conduction velocities showed impairment in the tibial and peroneal motor fibers. Auditory brain-stem response revealed elongated III-V interval. A cystometrogram disclosed a reflex neurogenic bladder. In the analysis of the fatty acid component of plasma sphingomyelin, the C26/C22, C25/C22, C24/C22 ratios were found to be increased, and the diagnosis of adrenomyeloneuropathy (AMN) was confirmed. The patient's mother was also found to be asymptomatic carrier of AMN on the basis of long chain fatty acid plasma levels. The MRI performed in his age of 29 years, showed marked spinal atrophy from low cervical to low thoracic regions and mild cerebellar atrophy. This findings seems to correspond with chronic progressive demyelination of spinal white matter such as pyramidal tract and fasciculus gracilis. PMID- 1914337 TI - [Study of cerebral circulation and cerebrospinal fluid dynamics in a patient with agenesis of the corpus callosum using 123I-IMP SPECT and cine-mode MRI]. AB - A right-handed, 77-year-old man, complaining of dizziness, was diagnosed as agenesis of the corpus callosum (ACC) by MRI, which demonstrated a complete defect of the corpus callosum (CC) with symmetrical enlargement of the posterior horns of the bilateral ventricles (colpocephy) and focal hypo-plasticity of the frontal lobes. Neurological examination revealed only mild impairment of mental function and poor transfer of tactile form-board learning from the right hand to the left hand. As to the cerebral circulation detected by 123I-IMP SPECT, isotope distribution corresponded to the MRI brain images, though the defects were clearly seen on the medial surfaces of the bilateral frontal lobes, so interhemispheric fissure seemed to be opened widely. IV-DSA revealed hypo vascularity in the anterior territory of the anterior cerebral arteries. These findings suggested that this localized defect was due to hypo-vascularity and focal hypo-plasticity of the frontal lobes. On the other hand, cine-mode MRI findings that no signal-void phenomenon was found between the third ventricle and the longitudinal fissure indicated no shunt in cerebrospinal fluid. PMID- 1914338 TI - [A case progressive dementia developed after repeated head trauma]. AB - A 46-year-old man who developed progressive dementia after repeated head trauma was reported. At the age of 30 and 36, he encountered traffic accidents and suffered from blows to his head. At 37 years old, he noticed impairment of memory and comprehension. At 41 years old, he was observed to become easily angered. These symptoms were slowly progressive, and at age 46 he was examined by us. He had no particular family history of dementia. Neurological examination revealed a disturbance of cognitive ability. The brain CT and MRI showed marked atrophy of the cerebral cortex, especially in the frontal and temporal lobes without any demonstrable lesions in the white matter. A single photon emission computed tomography (SPECT) using inhalation of 133Xenon disclosed hypoperfusion of the cerebral blood flow localized in the bilateral frontal and parietal lobes. He was supposed to suffer from juvenile Alzheimer's disease which might have developed after repeated head trauma. One similar case had been reported as a posttraumatic premature Alzheimer's disease. Finally, we discussed other causes of dementia including metabolic, infectious and vascular diseases. The present case also suggests that head trauma might be one of the provoking or promoting factors of Alzheimer's disease. PMID- 1914339 TI - Clinical pharmacokinetics of propafenone. AB - Propafenone is a class 1C antiarrhythmic agent which is administered as a racemate of S(+)- and R(-)-enantiomers. It is well absorbed and is predominantly bound to alpha 1-acid glycoprotein in the plasma. The enantiomers display stereoselective disposition characteristics, the R-enantiomer being cleared more quickly. The hepatic metabolism of propafenone is polymorphic and genetically determined: about 10% of Caucasians have a reduced capacity to hydroxylate the drug. This polymorphic metabolism accounts for the marked interindividual variability in the relationships between dose and concentration, and between concentration and pharmacodynamic effects. During long term administration, the metabolism is saturable in patients with the 'extensive metaboliser' phenotype, leading to accumulation of the parent compound. Propafenone blocks fast inward sodium channels in a frequency-dependent manner, and also has moderate beta blocking effects. Both the enantiomers and the 5-OH metabolite have a potency to block sodium channels comparable with that of the parent compound. The S enantiomer is a more potent beta-antagonist than the R-enantiomer. Propafenone typically slows conduction markedly but only modestly prolongs refractoriness. These cardiac effects are determined by the extent of its myocardial accumulation. The drug should be used with caution in patients with serious structural heart disease, as it may cause or aggravate life-threatening arrhythmias. Significant interactions occur when propafenone is coadministered with other drugs. It increases the plasma concentrations of digoxin, warfarin, metoprolol and propranolol as well as enhancing their respective pharmacodynamic effects. Doses of these drugs should therefore be decreased if they are coadministered with propafenone. PMID- 1914340 TI - Formation of active metabolites of anticonvulsant drugs. A review of their pharmacokinetic and therapeutic significance. AB - All of the commonly used anticonvulsants drugs, except possibly primidone, are cleared from the human body mainly by metabolism. The metabolites of phenytoin, phenobarbital and ethosuximide have so far not been shown to possess significant pharmacological activity. However, carbamazepine-10,11-epoxide, derived from carbamazepine, has anticonvulsant activity comparable with that of its progenitor, while oxcarbazepine, a new anticonvulsant congener of carbamazepine, is essentially a prodrug for its 10-hydroxy derivative. Valproic acid forms numerous metabolites through a variety of pathways; 2-en valproic acid, a beta oxidation derivative, probably contributes to its anticonvulsant action, though the extent of the contribution is uncertain. Another metabolite, 4-en-valproic acid, has been considered a possible hepatotoxin and teratogen. N-Methyl phenobarbital and primidone, though both anticonvulsants in their own right, are metabolised to phenobarbital, which probably mediates much of their antiseizure effect. Primidone also yields the weaker anticonvulsant phenylethylmalonamide. The various benzodiazepine anticonvulsants form numerous metabolites, some of which possess both antiseizure and other forms of pharmacological activity. As yet, there is little understanding of how best to interpret simultaneous plasma concentration measurements of anticonvulsant drug and its active metabolite (or metabolites) in the clinical situation, and the possible roles of anticonvulsant metabolites in the idiosyncratic toxicity of these drugs remain largely unexplored. PMID- 1914343 TI - Sex, age and alfentanil pharmacokinetics. PMID- 1914344 TI - Protein binding of phenytoin. PMID- 1914342 TI - Fetal drug metabolism and its possible clinical implications. AB - The ability of the human conceptus to metabolise xenobiotics during early gestation is now well established. Specific activities of liver enzymes have been demonstrated to exist in the late embryonic phase for numerous cytochrome P450 monooxygenases and many phase II enzymes such as glutathione-, N-acetyl-, sulpho- and uridine diphosphate-glucuronosyltransferase. As in the adult, fetal drug metabolism may function in a dual manner, either as a protective mechanism against chemical aggression when transforming active molecules into inactive ones, or as a toxifying system when transforming innocuous compounds into reactive metabolites. Recent advances in the understanding of enzyme variabilities at molecular and functional levels illustrate the necessity of studying these variations in the human fetus as well as in adults, since the combination of genetic, developmental and environmental factors seem to control fetal enzyme activities and ultimately determine the variability in individual susceptibility to chemicals in utero. Despite the scarcity of well documented cases of adverse fetal reactions resulting directly from metabolic toxicity, the clinical relevance of the potential role of biotransformation in generating fetal toxicity is a strong appeal to promote further studies dealing with the ontogeny of drug-metabolising capacity and its regulation. PMID- 1914345 TI - Primary empty sella syndrome in childhood: association with precocious puberty. AB - Primary empty sella syndrome has been considered an infrequent finding in childhood. One hundred and twelve cases have been reported in children ages 0.7 to 18 years. The frequency of primary empty sella ranged from 1% to 58%. Endocrine abnormalities were described in nearly all children while visual abnormalities were noted in only 6%. Growth hormone deficiency was the single most common hormonal dysfunction noted in children with primary empty sella. Precocious puberty has been rarely reported in association with primary empty sella. We report the case of a 7-1/2 year old girl with gonadotropin dependent central precocious puberty and a partially empty sella who had no other hypothalamic-pituitary dysfunction. We suggest that pubertal abnormalities be included among the endocrine disorders potentially associated with the primary empty sella syndrome. PMID- 1914346 TI - Diaper choice. Too costly to bury. AB - Diaper choice (cloth vs. disposable) has become a controversial issue with increased public concern for the environment. One hundred and twenty-four consecutive mothers were surveyed during the postpartum period about diaper choice. Six percent reported physician/nurse discussion of diaper choice during prenatal care. Seventy-seven percent planned to use disposable diapers only. Twenty-two percent planned to use cloth diapers or a combination of cloth and disposable diapers. Major reasons for choice of disposables included convenience, avoidance of safety pins and cleanliness. Mothers selecting cloth or a combination cited environmental concerns, low cost and cleanliness as reasons for their choice. Factors found to be significantly associated with choice of cloth or combination were older maternal age, use of cloth with other children, and perception that disposables are more expensive. No significant association could be demonstrated between diaper choice and several demographic variables, breastfeeding, or knowledge of the environmental impact of disposables. An educational intervention promoting the use of cloth diapers did not influence diaper choice at two months. Most mothers have made a diaper choice by the time an infant is born. Providers of prenatal care seldom discuss diaper choice with pregnant women. An educational intervention to promote choice of cloth diapers had no effect on the diaper choices made by our population. PMID- 1914341 TI - Clinical pharmacokinetics in patients with liver disease. AB - From considerations of hepatic physiology and pathology coupled with pharmacokinetic principles, it appears that altered drug elimination in liver disease may result from the following mechanisms: reduction in absolute cell mass, in cellular enzyme content and/or activity, in portal vein perfusion due to extrahepatic/intrahepatic shunting, or of portal perfusion of hepatocyte mass due to decreased portal flow or sinusoidal perfusion; increase in arterial perfusion relative to portal perfusion; preferential perfusion of the sinusoidal midzone and terminal zones by arterioles; potential for direct mixing of arterial blood within the space of Disse; reduced exchange across the endothelial lining; and impaired diffusion within the space of Disse. In general, oxidative drug metabolism is impaired in liver disease and the degree of impairment of oxidisation differs between drugs but correlates best with the degree of sinusoidal capillarisation, i.e. the degree of access of the drug from the sinusoid to the hepatocyte. Drug conjugation appears to be relatively unaffected by liver disease, whereas elimination by biliary excretion correlates best with the degree of intrahepatic shunting and not with sinusoidal capillarisation. As the latter should impair hepatocyte access of all compounds similarly, a potentially important mechanism could be impaired access of oxygen to hepatocytes as oxidative metabolism is much more sensitive to oxygen supply than are conjugation or biliary excretion. This suggests a potentially important therapeutic role for agents which increase the hepatic oxygen supply. Useful adjunctive strategies may also derive from the oxygen limitation hypothesis. Anaemia should be targeted as a critically important variable, as should oxygen carrying capacity, i.e. modification of the smoking habit. Additionally, enzyme inducers such as barbiturates may be used if overriding hypoxic constraints are removed by oxygen supplementation. Agents likely to seriously compromise arterial perfusion of the hepatic vascular bed should be avoided, e.g. those causing postural hypotension or vasospasm. Vasodilators can be used to actively promote arterial perfusion. While the effect of liver disease on drug handling is highly variable and difficult to predict, there are well recognised principles for modifying dosage. These include halving the dose of drugs given systemically (or of low clearance drugs given orally) and a 50 to 90% reduction in the dose of drugs with a high hepatic clearance given orally. Changes in the pharmacodynamic effects of drugs (either alone or in addition to pharmacokinetic changes) can also be profound, and awareness of this possibility should be increased. PMID- 1914347 TI - Relationship of fever magnitude to rate of serious bacterial infections in infants aged 4-8 weeks. AB - We correlated the height of fever with underlying infectious etiology in 683 consecutive febrile infants aged four to eight weeks who received outpatient evaluation for sepsis during a five-year period. The relative number of infants with fever was inversely proportional to fever height, as 51% had a temperature 38.1-38.9 degrees C, 45% had a temperature 39-39.9 degrees C, and 4% had a temperature greater than or equal to 40 degrees C [hyperpyrexia]. There were 34 cases of serious bacterial infections [SBI], including 16 cases of urinary tract infection, 8 cases of bacteremia, 6 cases of bacterial meningitis, and 4 cases of Salmonella enteritis. The rate of SBI increased in direct proportion to fever height, being 3.2% in those with a temperature 38.1-38.9 degrees C, 5.2% in those with a temperature 39-39.9 degrees C, and 26% in those with a temperature greater than or equal to 40 degrees C. The 6.8% rate of SBI in those with fever greater than or equal to 39 degrees C was significantly greater than the 3.2% rate in those with fever less than 39 degrees C [p less than 0.035]; and the 26% rate of SBI in those with hyperpyrexia was significantly greater than the 4.1% rate in those with fever less than 40 degrees C [p less than 0.000004]. In identifying those with SBI, the presence of hyperpyrexia had a sensitivity of 21%, specificity of 97%, positive-predictive value of 25%, and negative-predictive value of 96%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914348 TI - Medical knowledge of high school students. PMID- 1914349 TI - Education for changes in knowledge or behavior. PMID- 1914350 TI - Effective treatment for an adolescent with chronic fatigue syndrome. PMID- 1914351 TI - Screening for psychosocial dysfunction in pediatric dermatology practice. AB - The Pediatric Symptom Checklist, a brief psychosocial screening questionnaire, was used in a multi-center study of pediatric dermatology clinics (n = 377). Overall rates of positive screening indicated that approximately 13% of patients screened positive, a rate similar to findings in primary care pediatric settings. Examining the sample in greater detail demonstrated that children whose dermatologic disorder is perceived to have a greater impact on their appearance are at higher risk for psychosocial dysfunction. PMID- 1914352 TI - Tuberculosis in infancy: a case report. PMID- 1914353 TI - Churg-Strauss syndrome in a 14-year-old boy diagnosed by transbronchial lung biopsy. PMID- 1914354 TI - Magnetic resonance imaging in infants exposed to cocaine prenatally: a preliminary report. PMID- 1914355 TI - Maternal recall of infant birth weight. PMID- 1914356 TI - Survey of pediatricians' attitudes towards HIV testing of patients and health care professionals (HIV testing and pediatricians). PMID- 1914357 TI - The model drug approach in clinical pharmacology. PMID- 1914358 TI - Development of a successful fourth-year medical school elective course in therapeutics. PMID- 1914359 TI - Effects of protein and carbohydrate content of diet on drug conjugation. AB - Eight healthy subjects were fed a high-protein-low-carbohydrate diet and, after a 3-day washout period, an isocaloric low-protein-high-carbohydrate diet. They received acetaminophen and oxazepam, drugs metabolized primarily by conjugation, on days 11 and 13, respectively, of each diet. Changing the diets of subjects from the high-protein-low-carbohydrate diet to the low-protein-high-carbohydrate diet resulted in a 14% increase in urinary recovery of acetaminophen glucuronide and a 32% increase in urinary recovery of oxazepam glucuronide (p less than 0.05). The increases in glucuronidation were at the expense of other pathways of metabolism, and there were no significant changes in the metabolic clearance rates of acetaminophen and oxazepam. Mean renal clearances of acetaminophen glucuronide, acetaminophen sulfate, and oxazepam glucuronide decreased 45%, 32%, and 54%, respectively (p less than 0.05), when the subjects were switched to the low-protein-high-carbohydrate diet. PMID- 1914360 TI - Influence of amiodarone on genetically determined drug metabolism in humans. AB - Amiodarone has been shown to interact with the nongenetically determined hepatic elimination of several drugs, including phenytoin and digoxin. Its influence on genetically determined metabolic pathways has not been studied in humans. We examined the effects of oral amiodarone therapy on the genetically determined metabolism of isoniazid (N-acetyltransferase), mephenytoin (cytochrome P450MEPH), and dextromethorphan (CYP2D6). Eight patients with arrhythmias were studied before and 76 +/- 16 days after amiodarone (loading dose of 1000 mg/day for 10 days followed by a maintenance dose of 200 to 400 mg/day). Genetically determined enzyme activity was assessed indirectly by calculating the metabolic ratio (parent drug/metabolite in 8-hour urine for CYP2D6 and P450MEPH and N acetylisoniazid/isoniazid in plasma for N-acetyltransferase) after oral administration of the parent compounds. At the time of phenotyping, plasma concentrations of amiodarone and N-desethylamiodarone were 0.66 +/- 0.35 micrograms/ml and 0.65 +/- 0.26 micrograms/ml, respectively. Amiodarone increased the log(metabolic ratio) of dextromethorphan from a median of -2.5 (range, -2.9 to -2.0) to a median of -1.9 (range, -2.5 to -1.5; p less than 0.02) but did not alter the metabolic ratio of mephenytoin or isoniazid. The amount of dextromethorphan excreted in urine increased from a median of 0.084 mumol/8 hours (range, 0.041 to 0.161 mumol/8 hours) to a median of 0.205 mumol/8 hours (range, 0.064 to 0.288 mumol/8 hours; p less than 0.02) and the amount of its metabolite (dextrorphan) tended to decrease from a median of 26 mumol/8 hours (range, 15 to 37 mumol/8 hours) to a median of 20 mumol/8 hours (range, 7 to 27 mumol/8 hours; p less than 0.09).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914361 TI - The pharmacokinetics of recombinant double-chain t-PA (duteplase): effects of bolus injection, infusions, and administration by weight in patients with myocardial infarction. AB - The current mode of administration of recombinant tissue-type plasminogen activator (rt-PA) in acute myocardial infarction is rather complex, although the rationale for the different components of this scheme is not clearly established. We compared pharmacokinetics of a continuous infusion of 38.5 MU of Burroughs Wellcome t-PA (duteplase) over 90 minutes in nine patients (phase I) with a scheme including a 0.04 MU/kg bolus, a 60-minute 0.36 MU/kg lytic infusion and a 180-minute 0.21 MU/kg maintenance infusion in 15 patients with acute myocardial infarction (Phase II). t-PA activity and antigen were fitted in a one-compartment model from which model-dependent and model-independent parameters were derived. Clearance of t-PA activity was 1020 +/- 465 (mean +/- SD) ml/min in phase I and 1359 +/- 590 ml/min in phase II. Clearance of t-PA antigen was 666 +/- 230 ml/min in phase I and 704 +/- 199 ml/min in phase II. Clearance of activity was significantly (p less than 0.01) higher than of antigen. Clearance and steady state plasma levels showed a large interindividual variability (coefficient of variation, 56.4%), but this was significantly reduced by dosing by weight (coefficient of variation, 28.9%; p = 0.031). A 10% bolus in phase II shortened the time to reach 75% and 90% of the steady-state plasma level by 4 and 5 minutes, respectively, not significantly different from phase I. A simulation study showed that a bolus should be approximately 15% of the lytic dose to achieve a maximal level in the shortest period. PMID- 1914362 TI - Pharmacokinetics of 2',3'-dideoxyinosine in patients with severe human immunodeficiency infection. II. The effects of different oral formulations and the presence of other medications. AB - 2',3'-Dideoxyinosine (ddI) has shown activity against human immunodeficiency virus in phase I clinical trials. The drug is rapidly degraded by acid, however, thus raising questions as to the efficiency and reproducibility of its absorption after oral administration. This investigation studies the bioavailability of several oral dosage forms of ddI. When ddI was given to fasting patients as an oral solution with antacid, the bioavailability was 41% +/- 7% (mean +/- SEM). However, when given as buffered tablets, the bioavailability was considerably less (25% +/- 5%). The bioavailability increased slightly when the tablets were given with supplemental antacid (36% +/- 6%). Two enteric-coated preparations had reasonable bioavailability (36% +/- 5% and 26% +/- 5%), but the peak plasma level was much lower and occurred at a much later time than with the oral solution. When ddI was given as a premeasured powder containing sucrose and buffer to be reconstituted by the patient (the "sachet" preparation), the bioavailability was 29% +/- 6%. This was similar to that of the oral solution for this particular group of patients (30% +/- 7%). However, the bioavailability of the sachet was only 17% +/- 4% when administered with food. When the sachet was given to patients receiving ranitidine, no consistent change in bioavailability was noted. Also, no change in ddI pharmacokinetics was noted in patients receiving ganciclovir. PMID- 1914363 TI - Stable isotope method for studying transdermal drug absorption: the nicotine patch. AB - A stable isotope-labeled drug method was used to determine the absolute bioavailability and absorption kinetics of a transdermal nicotine-delivery system (TTS). TTSs are being developed as an adjunct to smoking-cessation therapy. Deuterium-labeled nicotine was infused for 24 hours simultaneously to TTS application in cigarette-abstinent smokers. In 11 subjects with good patch adhesion, an average systemic dose of 19 mg nicotine was delivered, with average absolute bioavailability of 82%. The rate of nicotine absorption was maximal between 6 and 12 hours after TTS application and declined thereafter, plateauing between 16 and 24 hours at 62% of the maximal rate. Ten percent of nicotine was absorbed after the TTS was removed, demonstrating a reservoir for nicotine in the skin. Our study demonstrates the applicability of stable isotope methods in understanding the clinical pharmacology of transdermal drugs. PMID- 1914364 TI - Relationship between the pharmacokinetics and iron excretion pharmacodynamics of the new oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with thalassemia. AB - Single-dose and steady-state pharmacokinetics of the new oral iron chelator, 1,2 dimethyl-3-hydroxypyrid-4-one (L1) were studied in 14 patients with thalassemia and correlated with iron excretion. Food prolongs the rate of absorption of L1, but it does not affect significantly the extent of absorption measured by the area under the plasma concentration-time curve. Similarly, it does not affect the chelation potential of the drug. The mean elimination half-life of the drug is 3 hours, suggesting that a divided dose every 8 hours may assure better chelation. Our steady-state studies reveal that urinary iron excretion is independently influenced by body iron load (measured by ferritin levels) and by steady-state trough concentrations of the drug. While patients were receiving an unchanged regimen of 75 mg/kg/day, we have detected a gradual and significant decrease in trough concentrations in the presence of unchanged patients' compliance monitored by the Medication Event Monitoring System, diaries, and pill count. These findings suggest self-induction of L1 metabolism or decreased absorption during long-term therapy. Because of the concentration-dependent iron excretion, patients may need increasing doses to achieve negative iron balance. PMID- 1914365 TI - Mexiletine effects on theophylline disposition. AB - The effect of mexiletine administration on steady-state plasma theophylline concentrations was studied in eight normal healthy men in a prospective open label nonrandomized two-way crossover trial. Repeated doses of 300 mg of sustained-release theophylline were given every 12 hours for 9 days. Mexiletine hydrochloride, 200 mg every 8 hours, was given for five consecutive doses starting on the morning of day 6. Mexiletine increased theophylline levels in all subjects. Mean predose (trough) levels rose from 8.1 +/- 0.1 microgram.ml-1 to 13.4 +/- 0.6 micrograms.ml-1 and AUC(0-12) from 96.8 +/- 9.1 to 160.2 +/- 3.7 micrograms.ml-1.hr. Plasma clearance was reduced by mexiletine from 44.7 +/- 5.1 to 25.4 +/- 1.2 ml.hr-1. Both N-demethylated metabolites of theophylline were decreased by 60% by mexiletine, whose levels remained within its therapeutic range. Theophylline levels returned to pre-mexiletine values when this drug was discontinued. Mexiletine reduces theophylline clearance and increases its plasma concentration by inhibiting N-demethylation of theophylline. Plasma theophylline levels should be monitored when mexiletine is added. PMID- 1914366 TI - Headache pain model for assessing and comparing the efficacy of over-the-counter analgesic agents. AB - To refine the assessment of over-the-counter analgesic agents in the treatment of muscle-contraction headache, we designed a single-dose model with attention to specific methodologic features and two relevant assessments--the percentage of subjects who achieve complete relief and the time until pain is no longer experienced. Subjects were randomly assigned to receive a single dose of 1000 mg acetaminophen, 1000 mg aspirin with 64 mg caffeine, or placebo. Under double blind conditions, subjects rated headache pain intensity and relief over 4 hours and provided a Comparative Evaluation at the end of the trial. Both active agents were significantly distinguished from placebo on the time-point analyses (p less than 0.05) and summary end point measurements (sum of pain intensity difference [SPID], total of pain relief, percentage of patients with complete relief, percentage of treatment failures, and the Comparative Evaluation), as well as causing a faster elimination of headache (p less than 0.05). The aspirin-caffeine combination was rated higher than acetaminophen on all summary measurements, particularly SPID (p less than 0.05), with significantly more patients obtaining complete relief with aspirin-caffeine (p less than 0.01) than with acetaminophen. We conclude that this headache pain model can be used to demonstrate the efficacy of over-the-counter analgesic agents and to assess their relative efficacy. PMID- 1914367 TI - Sibutramine in weight control: a dose-ranging, efficacy study. AB - We tested the safety and efficacy of sibutramine, 5 and 20 mg, and placebo on weight loss. Medication was added to caloric restriction, behavior modification, and exercise in a parallel-group, double-blind clinical trial. Participants were 130% to 180% of ideal body weight and in good health. The study lasted 12 weeks over Thanksgiving, Christmas, and New Year's Day. Weight loss during 8 weeks of study medication was: placebo, 1.4 +/- 2.1 kg (n = 19); 5 mg sibutramine, 2.9 +/- 2.3 kg (n = 18); and 20 mg sibutramine, 5.0 +/- 2.7 kg (n = 18) (p less than 0.05 sibutramine, 5 and 20 mg, versus placebo; p less than 0.05 sibutramine, 20 mg versus 5 mg). There is a significant dose-effect relationship. Five participants left the study before completion, all because of adverse events; placebo (one patient), 5 mg sibutramine (one patient), and 20 mg sibutramine (three patients). Sleep difficulties were noted by eight participants (20 mg sibutramine, seven patients; 5 mg, one patient; and placebo, no patients). Six of 21 participants receiving 20 mg complained of irritability, unusual impatience, or "excitation." Sibutramine, 5 and 20 mg, added to a multimodal program assisted participants in losing weight. PMID- 1914369 TI - Dose comparability of atenolol and betaxolol. PMID- 1914368 TI - The determinants of response to diltiazem in hypertension. AB - We examined factors (blood pressure, plasma renin activity, and age) influencing the antihypertensive response in essential hypertensive patients given 240 mg/day of slow-release diltiazem in an unblinded study after a placebo run-in period. Subjects provided a range of diastolic blood pressures (90 to 115 mm Hg), of age (31 to 70 years), and of plasma renin activity (0.1 to 2.7 ng angiotensin I/ml/hr) on a 70 to 150 mEq sodium diet. Blood pressure, plasma renin activity, and plasma diltiazem concentrations were measured after the first (n = 21) and final dose (n = 19) of 120 mg diltiazem, twice daily for 4 weeks. Multiple linear stepwise regression of change in blood pressure versus age, plasma renin activity, and baseline blood pressure showed baseline blood pressure was the only predictor of response (p = 0.0002). For each increase of 10 mm Hg in baseline pressure there was a 7 mm Hg greater decrease in diastolic blood pressure. We conclude that patient age and plasma renin activity are not clinically significant predictors of antihypertensive response to diltiazem in hypertension. PMID- 1914370 TI - Understanding the publication process of Clinical Pharmacology & Therapeutics. PMID- 1914372 TI - AF-DX 116, a cardioselective muscarinic antagonist in humans: pharmacodynamic and pharmacokinetic properties. AB - Effects of AF-DX 116, a cardioselective antagonist, on M cholinergic receptors (M ChR) were studied in healthy volunteers. Occupancy of M-ChR subtypes by drug present in plasma samples (radioreceptor assay) was compared with these effects. After an intravenous dose of AF-DX 116 saturating greater than 90% of cardiac M2 ChR, an increase in heart rate by 25 beats/min was observed. This cardiac receptor occupancy and effect wore off with a parallel time course within 10 hours. No inhibition of salivary flow was observed, coinciding with a lack of M3 ChR blockade in the radioreceptor assay. Beta-adrenergic receptor blockade by propranolol did not affect either of the effects. No indication for active metabolites or stereoselective drug metabolism was found comparing HPLC and receptor assay for drug concentrations in plasma. We conclude that AF-DX 116 may be a useful drug for the treatment of bradycardia. Its lack of troublesome side effects is the result of its selectivity for cardiac M-ChR. PMID- 1914371 TI - A pharmacodynamic interaction between caffeine and phenylpropanolamine. AB - The pharmacokinetic and pharmacodynamic interaction between caffeine and phenylpropanolamine has been investigated in six normal subjects in a double blind, placebo-controlled, Latin-square design study. After 3 days on a 100 mEq sodium, xanthine-free diet, fasting subjects were placed in a supine position and were given 25 mg phenylpropanolamine and placebo, 250 mg caffeine and placebo, or 25 mg phenylpropanolamine and 250 mg caffeine in random order. Blood pressure, pulse, plasma renin activity, and plasma catecholamine levels were measured before and for 3 hours after drug administration. Plasma and urinary phenylpropanolamine, caffeine, and caffeine metabolite levels were measured serially for 48 hours. Coadministration of caffeine and phenylpropanolamine produced an additive increase in blood pressure. This effect could not be explained by any pharmacokinetic interaction between the two drugs and occurred even though phenylpropanolamine attenuated the epinephrine and renin response to caffeine. These data suggest that a clinically relevant interaction between caffeine and phenylpropanolamine does occur in drug-free subjects and that this interaction cannot be explained by a mechanism involving the sympathetic or renin angiotensin systems. PMID- 1914373 TI - The effects of oral nifedipine on hepatic blood flow in humans. AB - Duplex ultrasonography was used to measure changes in hepatic blood flow in 13 healthy volunteers after they received single doses of 10 mg oral nifedipine and placebo. Blood flow was measured in the hepatic artery and branches of the portal and hepatic veins at baseline and 0.3, 0.6, 1, 1.5, 2, 3, 4, and 5 hours after drug administration. Cardiac output was also measured at baseline and 1, 2, and 3 hours after dosing. Blood flow initially increased in all three vessels 0.6 hour after administration of nifedipine (29%, 56%, and 31% in the hepatic artery, hepatic vein, and portal vein, respectively) compared with placebo. Flow rapidly returned to baseline in the hepatic artery and hepatic vein, whereas it appeared to remain elevated through 3 hours in the portal vein. Nifedipine administration resulted in an increase in cardiac output of 26%, 22%, and 14% above placebo at 1, 2, and 3 hours, respectively. No significant differences were detected in the systolic, diastolic, or mean arterial blood pressures after nifedipine or placebo. This study demonstrates that nifedipine increases hepatic blood flow in a transient nature and systemic hemodynamic parameters do not necessarily reflect specific organ responses. The nifedipine-induced change in blood flow should be considered when nifedipine is coadministered with high-clearance drugs, because systemic availability may be increased. PMID- 1914374 TI - Relation of systemic exposure to unbound etoposide and hematologic toxicity. AB - The pharmacodynamics of total and unbound etoposide was studied in 28 adult patients with solid tumors who were receiving etoposide and cisplatin combination chemotherapy. Etoposide plasma concentrations were determined by use of an HPLC method, and etoposide plasma protein binding was determined by equilibrium dialysis. Patients with higher systemic exposure experienced greater hematologic toxicity. The sigmoid maximum effect model with unbound systemic exposure performed better (i.e., lower residual sum of squares) than the model using total systemic exposure; in all patients (7043 versus 9755) and in the subset of patients who had not received previous chemotherapy (1986 versus 3664). The model estimates for unbound systemic exposure were more precisely estimated than for total systemic exposure (e.g., coefficient of variation for the area under the concentration-time curve producing half of the maximal effect = 51% for total drug versus 21% for unbound drug). These findings indicate that the hematologic toxicity of etoposide is better correlated with systemic exposure to unbound drug than total drug, which may be of clinical importance because of the variable plasma protein binding of etoposide. PMID- 1914375 TI - Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans. AB - The effects of grapefruit juice (150 ml at -15, -10, -1/4, +5, and +10 hours) and cimetidine (200 mg at the same times) on the stereoselective pharmacokinetics and effects of 20 mg oral racemic nitrendipine were investigated in a placebo controlled crossover study in nine healthy men. In all subjects the AUC of racemic nitrendipine was increased by grapefruit juice (mean increase 106%; 95% confidence interval 64% to 158%) and cimetidine treatment (+154%; 95% confidence interval 77% to 265%). Comparable results were obtained for the peak plasma drug concentration and for both parameters of (S)- and (R)-nitrendipine. There were highly significant differences in the area under the concentration-time curve and peak plasma drug concentration between enantiomers within all treatments. Grapefruit juice had no effect on this stereoselectivity, but cimetidine increased the mean S/R ratio of areas under the curve (2.25) by 20% (95% confidence interval 12% to 29%) compared with placebo treatment (1.89). Half lives and time to reach peak concentration of the enantiomers were not different within and between treatments. There were no consistent effects on blood pressure with all treatments, but in most subjects there was a small temporary increase in heart rate after intake of nitrendipine. Grapefruit juice and cimetidine did not affect these hemodynamic parameters and did not cause additional adverse effects. PMID- 1914376 TI - Influence of menstrual cycle and gender on alprazolam pharmacokinetics. AB - The effects of menstrual cycle phases and gender on alprazolam pharmacokinetics were evaluated in normal volunteers. Alprazolam (1 mg) was administered to seven women during the late follicular and luteal phases of the menstrual cycle and to eight men on one occasion. No difference in alprazolam pharmacokinetic parameters was observed during the menstrual cycle phases. Mean alprazolam clearance (+/- SD) was 0.0037 +/- 0.0009 ml/hr during the follicular phase and 0.0036 +/- 0.001 ml/hr during the luteal phase (p greater than 0.05, difference not significant). With use of weight as a covariant, there was no difference in alprazolam pharmacokinetic parameters between women and men. Mean alprazolam clearance (+/- SD) was 0.0036 +/- 0.0009 ml/hr in women compared with 0.0041 +/- 0.0006 ml/hr in men (p greater than 0.05, difference not significant). Although alprazolam metabolism was similar on the 2 days tested, alterations may occur at other times during the menstrual cycle. Further investigation is needed to understand the effects of menstrual cycle phases and gender on drug metabolism. PMID- 1914377 TI - The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine. AB - The disposition of oxcarbazepine was studied in 12 young and 12 elderly healthy male and 12 young and 12 elderly healthy female volunteers, with emphasis on the influence of age. Oxcarbazepine was administered as a single dose of either 300 mg (men) or 600 mg (women), followed by multiple-dose (300 mg) administration twice a day for 7 days (men) or 6 days (women). Semilogarithmic plasma concentration-time curves showed an increasing decline at decreasing concentrations. Accumulation of the pharmacologically active metabolite monohydroxycarbamazepine was found to be more than one would anticipate on the basis of linear and unchanged pharmacokinetics. Saturation did not seem to occur at the level of renal excretion. No apparent differences between male and female volunteers were observed. A significant higher maximum concentration, higher area under the curve parameters, and a lower elimination rate constant were observed in the elderly. These observations are in line with a smaller renal clearance of monohydroxycarbamazepine in the elderly group. In a clinical situation, these age related differences are not likely to have important implications. In general, treatment with oxcarbazepine was well tolerated. PMID- 1914378 TI - Pharmacokinetics of galanthamine in humans and corresponding cholinesterase inhibition. AB - Measurements were done to determine the plasma concentrations of galanthamine and two of its metabolites, as well as the corresponding inhibition of acetylcholinesterase activity in erythrocytes after applying 5 and 10 mg galanthamine hydrobromide as a constant-rate intravenous infusion for 30 minutes and single oral doses of 10 mg in eight healthy male volunteers. The data obtained revealed first-order pharmacokinetics, complete oral bioavailability, and a mean terminal half-life of 5.68 hours (95% confidence interval, 5.17 to 6.25 hours). Renal clearance accounted for only 25% of the total plasma clearance (CL = 0.34 L.kg-1.hr-1). Only negligible quantities of the putative metabolites, epigalanthamine and galanthaminone, were detected in blood and urine. The inhibition of acetylcholinesterase activity was closely correlated with the pharmacokinetics of galanthamine, a median maximal value of 53% being achieved by applying 10 mg galanthamine intravenously. Analysis of in vitro and ex vivo concentration responses revealed no differences, indicating that no metabolites of galanthamine exert additional inhibition of acetylcholinesterase activity. PMID- 1914379 TI - Dose-ranging study of the novel recombinant plasminogen activator BM 06.022 in healthy volunteers. AB - The novel recombinant plasminogen activator BM 06.022 consists of the kringle 2 and protease domains of human tissue-type plasminogen activator and is unglycosylated because of its expression in Escherichia coli cells. Pharmacokinetics for activity and hemostatic effects of BM 06.022 were studied in 18 healthy male volunteers after an intravenous bolus injection over 2 minutes. BM 06.022 was administered successively at doses of 0.1125, 0.55, 2.2, 3.3, 4.4, and 5.5 MU to three volunteers. Plasma fibrinogen was unchanged; effects of BM 06.022 were observed on plasminogen only at higher doses, and dose-dependent effects were seen on alpha 2-antiplasmin and fibrin D-dimers. The concentration of plasminogen and alpha 2-antiplasmin was 87% +/- 3% and 79% +/- 3%, respectively, of baseline 2 hours after injection of 5.5 MU of BM 06.022. Fibrin D-dimers were highest with 1147 +/- 380 ng/ml at 5.5 MU of BM 06.022. The area under the activity concentration-time curve (AUC) increased dose-dependently and linearly. At 5.5 MU of BM 06.022, the AUC was 313 +/- 47 IU.hr.ml-1, the total plasma clearance was 306 +/- 40 ml/min, and the half-life was 14.4 +/- 1.1 minutes. PMID- 1914381 TI - Disposition of drugs in cystic fibrosis. II. Hepatic blood flow. AB - To determine whether the increased clearance of high extraction-ratio drugs in cystic fibrosis is caused by an increase in hepatic blood flow, the blood flow in main branches of the hepatic vein and portal vein was measured by use of noninvasive duplex ultrasound scanning in 10 adult subjects with cystic fibrosis and in 10 healthy age-, gender-, and height-matched control subjects. No statistically significant differences between subjects with cystic fibrosis and control subjects were detected in either the hepatic vein (217 +/- 103 ml/min for subjects with cystic fibrosis versus 211 +/- 135 ml/min for control subjects) or the portal vein (205 +/- 114 ml/min for subjects with cystic fibrosis versus 190 +/- 101 ml/min for control subjects) blood flows. These data indicate that a large (greater than or equal to 100%) increase in the clearance of high extraction-ratio drugs in patients with cystic fibrosis is unlikely to be primarily caused by an increase in hepatic blood flow. It is probable that alternative mechanisms such as enhanced secretory or metabolic pathways account in large part for increases in clearance of high extraction-ratio drugs. PMID- 1914380 TI - Single-dose pharmacokinetics of 14C-lovastatin in chronic renal failure. AB - An open study on the pharmacokinetics of lovastatin was conducted in six patients with chronic renal failure (mean creatinine clearance, 0.40 ml/sec; range, 0.20 to 0.65 ml/sec) and seven healthy subjects. Plasma levels of 3-hydroxy-3 methylglutaryl-coenzyme reductase inhibitory activity (total and active) and total radioactivity were determined over 168 hours after a single dose of 80 mg 14C-lovastatin. The mean area under the plasma concentration-time curve for active inhibitors were 606 +/- 346 and 282 +/- 138 ngEq.hr/ml (p = 0.04) in patients and control subjects, respectively. Total inhibitors in plasma and total radioactivity were similarly elevated in patients with chronic renal failure. Results indicate that patients with severe renal dysfunction have altered elimination kinetics of lovastatin. Current ongoing clinical studies in patients with renal dysfunction will allow better assessment of the pharmacodynamic meaning of our observations. PMID- 1914382 TI - Nicotine absorption and the subjective and physiologic effects of nicotine toothpicks. AB - This study investigated a new tobacco-free smoking substitute intended to provide not only the nicotine but also, to some extent, the manipulative component of the smoking act. Nicotine uptake and cardiovascular and subjective effects of nicotine-containing toothpicks (4 mg) were compared with those of nicotine chewing gum (4 mg). After the two products were chewed for 5 minutes, the nicotine uptake from the toothpick was twofold that of the gum. However, comparing the total nicotine deliveries of both products, they are quite similar. The cardiovascular parameters showed a clear nicotine effect, but they did not differentiate between the two products. Among the subjective parameters there were only minor differentiations. However, the potential advantages of the toothpicks: (1) dental care and (2) a possible substitute for the manipulative component of the smoking act, remain to be verified in further experiments. PMID- 1914383 TI - Nicotine metabolism in humans. PMID- 1914384 TI - Effects of smoking on caffeine urinary metabolites. PMID- 1914385 TI - The radiogenic hazards of working in a radiology department. PMID- 1914386 TI - The value of negative needle biopsy in suspected operable lung cancer. AB - The value of needle biopsy (NB) of pulmonary masses in patients unsuitable for surgery is well established. The presence of malignant cells confirms the diagnosis and thus aids management. We have reviewed 196 patients aged over 40 years with a solitary pulmonary mass suspected of being operable lung cancer to assess the effect of a negative NB result on the management. Malignant cells were discovered in 148 patients and diagnoses of infection were made in a further 10. In 38 patients no malignant cells were identified. Nineteen patients proceeded to thoracotomy and 13 of these had malignant disease. Nine others had further needle biopsies and eight of these had malignancy. Ten patients were followed up without any further intervention and four of these eventually proved to have malignancy. Thus of the 38 patients with no malignant cells on NB but no definite benign diagnosis, 25 had malignancy, six had benign disease and seven had presumed benign disease. In this series NB provided a definite benign diagnosis in 5.1% of patients. From this study it may be concluded that if a solitary pulmonary nodule has a high clinical suspicion of malignancy and the patient is a candidate for surgery, NB is of limited value in management. PMID- 1914387 TI - The radiological appearances of 'Q' fever pneumonia. AB - The chest film findings in a series of 21 cases of serologically proven 'Q' fever with radiological evidence of pneumonia were reviewed retrospectively. Segmental opacities which were slow to clear, often with loss of volume and sometimes lobar consolidation, were the most usual findings. Lesions were occasionally multiple and sometimes became rounded during resolution. The appearances were not considered sufficiently distinctive to allow the diagnosis to be made in the acute phase of the illness, although the appearance of round pneumonias which are slow to resolve should alert the radiologist to this possible diagnosis. The findings are discussed in relation to previously reported series. PMID- 1914388 TI - Diaphragmatic muscular bundles (slips): ultrasound evaluation of incidence and appearance. AB - Diaphragmatic muscular bundles (slips) connect the central tendon of the diaphragm to the inner aspect of the lower thoracic cage. They cause hepatic invaginations which may be visualized at ultrasound (US) or computed tomography. Two hundred patients underwent prospective US of the diaphragm and liver to determine the incidence and characteristics of slips. The incidence was 15%, rising to 30% in those aged 80 years and over. Slips average 1.2 cm in depth (range 0.1-3.6 cm) and their occurrence has no racial or sexual bias. Multiple slips were seen in 4% of patients, all females. Slips are echogenic and have a variety of appearances, typically nodular on transverse section and strand-like longitudinally. Knowledge of these structures will avoid confusion with liver and peridiaphragmatic pathology. PMID- 1914389 TI - Evaluation of magnification and paddle compression techniques in the assessment of mammographic screening detected abnormalities. AB - Between February 1988 and December 1989, 8.6% of all women who presented to the South East London Breast Screening Centre for mammography were recalled for assessment. Magnification or paddle compression techniques were used in the assessment of 39% of these patients. The aim of the study was to evaluate the improvement in mammographic specificity provided by these 'special views'. Three hundred and thirty cases were reviewed. The basic mammograms were assessed both alone and together with the special views, and the mammographic findings were scored according to the index of suspicion for malignancy. Special views were felt to be helpful when they led to an increase in mammographic specificity. It was found that special views increased mammographic specificity in 50.8% of cases. Sixteen 'equivocal' diagnoses became 'normal' or 'benign' and 15 of these patients avoided surgical biopsy. Twelve 'equivocal' diagnoses became 'malignant', which helped surgical planning, and in all 12 cases, histology confirmed the diagnosis of malignancy. It is felt that 'special views' are necessary for the complete mammographic assessment of many screen-detected abnormalities. PMID- 1914390 TI - Computed tomography of the brain: does contrast enhancement really help? AB - The contribution of intravenous contrast medium to the final diagnosis was assessed in 300 patients undergoing routine axial computed tomography (CT) of the brain. Two-hundred-and-twelve patients presented with symptoms or signs suggesting focal intracranial pathology and 88 with non-focal features. A total of 110 post-contrast scans were abnormal. The differential diagnosis was altered in 15 patients (5%) following contrast enhancement, 13 of whom presented with focal symptoms and signs. In three patients with normal plain scans and symptoms and signs suggesting focal intracranial pathology abnormalities were only seen after contrast medium and in only one was the lesion surgically treatable. In a further 15 patients (5%) contrast enhancement increased the certainty of the diagnosis that had been made on the uncontrasted scan. We feel that when the uncontrasted scan is normal contrast enhancement is only helpful in a limited number of patients with symptoms and signs suggesting focal intracranial pathology. Contrast enhancement is still important in differentiating abnormalities seen on the unenhanced scan even with modern high resolution CT scanners. PMID- 1914391 TI - Syringohydromyelia: radiological evaluation of 82 patients in a developing country. AB - A series of 82 patients presenting with syringohydromyelia and confirmed at operation were studied by conventional radiological techniques and computed tomography (CT). Cord collapse was demonstrated in 71% of the patients with wide bony canals and only 11% of patients with normal bony canals. It was most reliably shown with high resolution CT. Intrathecal CT metrizamide myelography (CTMM) failed to demonstrate contrast percolation into many cavities shown in the plain scans. Obliteration of the subarachnoid space at C1-2 levels appreciated in the plain scans strongly indicated coexisting tonsillar herniation, making CTMM unnecessary. In almost all patients, CTMM was found to be non-contributory if the high resolution plain CT scan failed to reveal cord cavitation. PMID- 1914392 TI - The role of early sonography in the management of the acute abdomen. AB - A prospective study was set up in a busy teaching hospital to evaluate the role of a 24 h emergency ultrasonography service in patients presenting with acute abdominal pain. Seventy-five patients due for admission via the accident and emergency department with acute onset of upper or lower abdominal pain were imaged at the request of our surgical colleagues. In 14 patients (18.7%), a diagnosis was made up by sonographic examination which had not been clinically expected. Twelve of this group were female with gynaecological pathology and all 14 had their proposed emergency surgery deferred following the sonographic examination. In 26 patients (34.7%), sonography confirmed the first diagnosis suspected clinically and in nine cases (12%) confirmed the second or third differential diagnosis. Sonography made no contribution to the diagnosis in 24 patients (32%) and in two cases (2.6%) was considered misleading. The results of this study demonstrate that emergency ultrasonography is most useful in the diagnosis of female patients presenting with mid to lower abdominal pain. PMID- 1914393 TI - The thick common bile duct in pyogenic cholangitis. AB - The paper describes thickening of the wall of the common bile duct in acute pyogenic cholangitis demonstrated by ultrasound. The abnormality appears as a hypoechoic stripe lying internal to the echogenic line of the normal common bile duct. The clinical features of acute cholangitis may be atypical and this new sign should be of value in these difficult cases. PMID- 1914394 TI - Survival after transhepatic embolization of gastro-oesophageal varices. AB - Twenty-five transhepatic embolization procedures were carried out between 1984 and 1989 on 24 patients with life-threatening haemorrhage from gastric or oesophageal varices after conservative methods had failed. There were two deaths related to the procedure and another 17 patients died during the following year. There were five survivors at 1 year, four are alive and well 4 years later, the fifth was lost to follow-up at 2 1/2 years. Survival at 1 year was not affected by a number of factors present at the time of embolization including the underlying liver pathology, the patient's age, platelet count, blood urea, serum bilirubin or the embolization technique. However, survival at 1 year was related to more normal coagulation values (international normalized ratios, INR) P less than 0.005, normal serum aspartate aminotransferase levels (P less than 0.025) and Pugh's grade A (P less than 0.01). We conclude that this procedure can prolong the survival of a small proportion of good risk patients. PMID- 1914395 TI - Pre-operative radiological and clinical assessment of hepatic tumours--is biopsy necessary? AB - The pre-operative investigations of 72 consecutive patients who underwent liver resection for hepatic tumours have been reviewed. A combination of clinical, biochemical and radiological findings correctly predicted histology in 93% of cases (the benign or malignant nature in 97%). Biopsy was performed in only 20 patients. Five of the biopsy reports were incorrect (75% accuracy, benign or malignant nature accuracy 90%). Although guided biopsy can be performed during radiological assessment of focal hepatic lesions we argue that it is rarely indicated and can be misleading in patients proceeding to hepatic resection. PMID- 1914396 TI - Use of air in double contrast barium enema--is it still acceptable? AB - There is conflicting evidence regarding the benefit of using carbon dioxide in a double contrast barium enema. In a double blind prospective study, 200 patients undergoing out-patient double contrast barium enemas (DCBE) were randomly allocated to receive either air or carbon dioxide (CO2) insufflation. After 24 h they were requested to complete and return a questionnaire regarding abdominal pain and distension experienced following the examination. The use of CO2 reduced the incidence of severe post-DCBE pain from 27% to 7%. There was a higher incidence of severe pain in younger patients, regardless of which gas was used. The incidence of severe pain following DCBE was unrelated to the presence or absence of abdominal pain as part of the patient's symptomatology. In the light of these findings we advocate the routine use of CO2 in DCBE. PMID- 1914397 TI - Complications of direct brachial artery puncture for arteriography: a comparison of techniques. AB - Direct brachial artery puncture is used increasingly for day-case arteriography and patients with severe aorto-iliac disease. In expert hands low complication rates are reported, but the risks of brachial artery puncture may be higher when it is performed by less experienced operators. Over a 2 year period 49 direct brachial artery punctures were performed for arteriography. In 27 cases catheters were inserted directly over a guide-wire via a variable puncture site. In 22 cases catheters were inserted through an introducer sheath via a high brachial puncture. Significant complications requiring active treatment or surgical intervention occurred in three (11%) cases where direct catheter insertion was used. There were no complications when an introducer sheath was used. Percutaneous high brachial aortography using an introducer sheath is a safer technique when brachial artery puncture is performed infrequently. PMID- 1914398 TI - Plain film reporting in the UK. AB - A survey has been carried out to investigate the extent of non-reporting and delayed reporting of plain radiographs in UK hospitals. The survey took the form of a confidential postal questionnaire to all consultant radiologists in the UK. Five hundred and sixty-five replies were included in the study, representing 45% of the total consultant workforce. The majority of respondents (58%) indicated their belief that all plain films should be reported by a radiologist. However, only 16% stated that all films were reported, and 22% stated that more than 10% of films were never reported. The principal categories of films not reported were: out of date, dental, fracture clinic follow-up and orthopaedic out patients. The commonest reason given for non-reporting was the near certainty that the report would be too late to influence clinical management. Although such a survey cannot be used to estimate precise prevalence, it does show that large numbers of radiological examinations go unreported, or are reported after the films have been returned from the referring clinician. The level of non-reporting is at variance with the stated ideals of the majority of radiologists questioned. Further research is needed to establish the clinical importance of present levels of non-reporting and delayed reporting. PMID- 1914399 TI - Percutaneous transcaval tumour biopsy using a 'road-map' technique. AB - The 'road-map' facility available on some of the commercially available digital subtraction angiography units is usually used to aid in the selective catheterization of a vessel during arteriography. We describe its use in the percutaneous transcaval biopsy of tumour within the inferior vena cava (IVC). PMID- 1914400 TI - Technical report: an injection technique for repositioning subclavian catheters. AB - Malpositioned central venous catheters need to be repositioned so as to avoid local toxicity from chemotherapeutic and other agents and to prevent venous thrombosis. We describe a simple, safe and effective technique for repositioning silicone central venous catheters, by using a hand injection of sterile saline. It was successful in all nine patients in whom it was attempted, with no complications. Five catheters were single lumen and four were double lumen. We feel that this method should be attempted prior to the use of more invasive techniques. PMID- 1914401 TI - Case report: vascular anomaly in Dieulafoy's disease. AB - We present a case of a vascular anomaly with Dieulafoy's disease in a young man. The diagnosis was made by coeliac and selective left gastric angiography after endoscopy, laparotomy and angiography had failed to detect the lesion. The patient was treated successfully by laparotomy and resection of the bleeding area in the stomach. This is the second report of a vascular anomaly with Dieulafoy's disease. PMID- 1914402 TI - Case report: multiple intracranial hydatid cysts with post-operative dissemination. AB - A case of primary multiple intracranial hydatid cysts is reported. The cysts were both supratentorial and infratentorial. One showed rim enhancement and perifocal oedema. Post-operatively, the number and size of cysts increased, possibly because of intraoperative rupture. PMID- 1914403 TI - Case report: cerebrospinal fluid fistula--a rare complication of myelography. AB - A case of a cerebrospinal fluid fistula developing following a lumbar puncture done for myelography is described. Radiographic documentation was obtained by a sinogram using an oily contrast medium. The exact aetiology of the fistula was undetermined, however, the large calibre of the spinal needle used for lumbar puncture as well as the patient's decubitus ulcer in the early post-myelography state may have had a role to play. The presence of a low grade infection also remains a possibility as the needle used was of an autoclaved, reusable type. PMID- 1914405 TI - Case report: the ultrasound and Doppler appearances of pelvic varices. AB - Dilatation of the veins of the broad ligament and ovarian plexi cause a very specific clinical entity called the pelvic congestion or pelvic pain syndrome. The ultrasound and Doppler appearances of this condition are unique and should be easily recognized. We describe these appearances in one patient and review the literature. PMID- 1914404 TI - Case report: an oxidized cellulose granuloma--another hepatic pseudotumour? AB - We report a patient who presented with right upper abdominal pain and jaundice 4 months after an elective cholecystectomy. A clinical diagnosis of choledocholithiasis was supported by imaging. Ultrasound and computed tomography also led us to diagnose an incidental liver tumour which guided biopsy demonstrated as an oxidized cellulose ('Oxycell') granuloma. PMID- 1914406 TI - Case report: pararenal extramedullary haematopoietic tissue--an unusual manifestation of myelofibrosis. AB - The case of a 41-year-old man with myelofibrosis who presented with anaemia and splenomegaly is described. Ultrasound examination revealed several multiple circumscribed hypoechoic masses adjacent to both kidneys. The lesions were confirmed by computed tomography (CT) and biopsy of them revealed extramedullary haematopoietic tissue. PMID- 1914407 TI - Pericardial cyst in a patient with acute chest pain. PMID- 1914408 TI - Patient dose reduction. PMID- 1914409 TI - US in predicting non-visualization of the gall-bladder on cholecystography. PMID- 1914410 TI - Diffuse systemic sclerosis and related diseases in Thailand. AB - Diffuse systemic sclerosis and the related syndromes were diagnosed in 115 patients during 1977-1987. Sixty-nine patients were available for clinical evaluation and analysis. These included 46 patients with diffuse systemic sclerosis, 2 with limited cutaneous systemic sclerosis, 2 with linear scleroderma, 18 with overlap syndrome (OS), and one with primary Raynaud's disease. The major clinical manifestations among the diffuse scleroderma patients were the involvement of the following systems; cutaneous (93.3%), musculoskeletal (69.6%), gastrointestinal (54.3%), and pulmonary (43.3%) while renal involvement (4.3%) was less common. Antinuclear antibodies were found in 89.7% with predominating speckle pattern (86.2%) and anti Scl 70 antibody (40.6%). In contrast to the Western series, HLA-DR2 was significantly increased in our diffuse systemic sclerosis patients (p less than 0.01). Among the 18 OS patients, the involvement of pulmonary system (44.4%) was the major cause of morbidity and renal involvement (55.6%) was found frequently although it was clinically mild. In conclusion, our diffuse systemic sclerosis and related diseases patients seem to have milder clinical manifestations than those of the Western series. PMID- 1914411 TI - Arthropathy associated with palmoplantar pustulosis. AB - A survey of 170 patients with a diagnosis of palmoplantar pustulosis (PPP) has been undertaken. Detailed family histories of our patients were compiled, dermatological and rheumatological examinations were made. Radiography was performed in patients with clinical suspicions of spinal and/or sacroiliacal, sternoclavicular and sternocostal joint involvement. Active chest-wall symptoms were screened by scintigraphy. Twenty-five patients (16 females, 9 males, with an age range of 32-66, mean 51 years) had some rheumatic complaints. Fifteen of them (60%) had anterior chest-wall involvement, 6 (24%) sacroiliitis (3 of whom also had AS) and 11 (44%) peripheral arthropathy. Six other patients suffered from transient and migratory joint pain. The joint disease was mild in all but 6 cases. Laboratory tests showed increased ESR in 6 patients (24%); only 3 of these patients had elevated CRP. A slightly elevated haptoglobin and/or orosomucoid were found in 12 cases (48%). Elevated IgA was present in 4, IgG in 2 and IgM in 1 patient. Fungal and bacteriological cultures of the skin were negative. A family history of psoriasis was present in 4 patients (16%), of psoriatic arthropathy in 1 patients (4%) and of PPP in 2 patients (8%). Six patients (24%) had concomitant psoriasis. No association between PPP H1a-AC antigens was found. A high incidence of HLA-B27 antigen, present in 8 patients (32%), was documented. A similar association with HLA-B27 has been found in patients with psoriatic arthritis (16). The feeble association with HLA-B13,-17,-37 and CW6 found in psoriasis was not present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914412 TI - Bernardino Ramazzini (1633-1714) physician of tradesmen, and possibly one of the "fathers" of sports medicine. PMID- 1914413 TI - Relationship between severity and clinical importance of symptoms in osteoarthritis. AB - Seventeen patients with primary osteoarthritis of the knee were evaluated with respect to the severity and clinical importance of pain, stiffness and physical function during the conduct of a double-blind randomized controlled trial of flurbiprofen SR versus diclofenac sodium SR using the WOMAC Osteoarthritis Index. Mean importance scores were similar for items within the same dimension as well as between items in different dimensions. In general, low levels of correlation were noted between the severity and importance of symptoms. Analysis of individual WOMAC items within a given subscale indicated that, although highly correlated, they differed from one another. Factor analysis further supported the contention that scores from items within a subscale could be summated into subscale scores. These observations are of importance in the weighting and aggregation of items within discrete dimensions and have the potential for reducing sample size requirements for clinical trials in osteoarthritis. PMID- 1914414 TI - Hyperparathyroidism in proximal femur fractures biological and histomorphometric study in 21 patients over 75 years old. AB - Proximal femur fractures in elderly people are more and more frequent. Falls and senile bone disorders are the risk factors of this fracture. In order to understand the mechanisms of these bone disorders, we studied 21 consecutive patients with this fracture using bone histomorphometry. Measurements of serum intact parathormone (PTH), 25-(OH)-vitamin D, 1,25-(OH) 2-vitamin D and osteocalcin have been performed in these 21 patients, included in a larger series. We excluded patients with renal failure (serum creatinine greater than 140 mumols/l), cancer, or previous metabolic bone disease. There were 19 female and 2 male patients, ranging from 75 to 96 years, (mean 84.9). We found a low frequency of cortical (2/21) and trabecular (3/21) osteoporosis. There was no case of clearcut osteomalacia. Following histomorphometric bone study, two patients showed a typical pattern of hyperparathyroidism, and in a third one, this condition seemed very likely. In these three patients who were among the oldest, and who had high levels of serum PTH, chronic renal failure and primary hyperparathyroidism could be excluded. High bone remodeling was frequent in our patients, as reflected by the enhancement of eroded surfaces (13 cases) and of osteoid thickness (7 cases). Intact PTH level was elevated in our series compared to normal values in adults (in accordance to the PTH elevation in the case control study in a larger series). These findings suggest a major role of a secondary hyperparathyroidism in senile bone disorders favoring proximal femur fractures. This hyperparathyroidism is probably secondary to mild calcium and vitamin D deficiency. It may lead to architectural bone changes favoring this fracture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914415 TI - Effect of interleukin-1 on hyaluronate synthesis by synovial fibroblastic cells. AB - Interleukin-1 (IL-1) stimulates fibroblast-mediated hyaluronate (HA) synthesis in vitro. In the present study the degree of polymerization of such HA was studied using HPLC (high performance liquid chromatography) with a size exclusion column combined with 125I-HABP assay used to measure the HA concentration in various HA molecular weight fractions separated using HPLC. IL-1 stimulated HA was more polydisperse than that produced by resting fibroblasts with a molecular weight varying from more than 4 x 10(6) daltons to less than 7.1 x 10(3) daltons. This IL-1 effect may contribute to the low molecular weight HA produced by freshly explanted arthritic synovial tissue and to the low viscosity of arthritic synovial fluid in vivo. PMID- 1914417 TI - Comparisons of spontaneous pain and tenderness in patients with primary fibromyalgia. AB - Pain was assessed in 47 patients with fibromyalgia in the University Rheumatology Clinic in Basle with the aid of three different techniques. First, a simple visual analog scale was used, later a body diagram on which patients could indicate pain separately in different regions of the body (pain score) and, finally, dolorimetric measurements at 56 typical PFS tender points. After four weeks of therapy, pain was again scored by patients using these techniques. The changes in assessment were compared with the aid of Spearman correlation. Data recorded with the aid of the body diagram correlated better with dolorimetric findings than did the results obtained from a simple visual analog scale. The severity of the disease can be more objectively assessed using these three techniques than it can using only the visual analog scale. In particular, the pain score and dolorimetry make possible a clear assessment of the value of therapeutic regimens. PMID- 1914416 TI - Protrusio acetabuli in adult rheumatoid arthritis. AB - In a retrospective study of 100 patients with adult rheumatoid arthritis, 23/100 (23%) were found presenting protrusio acetabuli (PA). PA of the hips was present in 28/193 (14.5%). This complication was more frequent in females, with 19/23 cases (82%), and its presence and severity were associated with longer duration of disease. On analysing the probable relationship between PA and glucocorticoid intake, no statistically significant differences were found between patients who had received such drugs and those who had not. With the method employed and in a selected rheumatoid arthritis population, PA was found in high prevalence. PMID- 1914418 TI - Functional testing in lumbar nerve root compression syndromes. An evaluation in patients with normal neurological findings. AB - A functional test using downhill walking was evaluated in relation to the myelographical examination in 33 patients with a suspected lumbar nerve root compression syndrome despite normal neurological findings. Any changes of motor or reflex signs or of straight leg raising were accepted as test results. They were noted in a decision matrix and the positive and negative predictive value (PPV and NPV, respectively) calculated. The PPV of any deterioration of the neurological status resulting from the test as a sign of abnormal myelographical findings was calculated to be approximately 85 per cent, the corresponding NPVs being approximately 50 per cent. In its present form, this functional test is inadequate as a screening procedure in these patients. PMID- 1914419 TI - Anti-thyroid microsomal antibody in synovial fluid as a revealing feature of seronegative autoimmune thyroiditis. AB - Two cases of recurrent monoarthritis are described in which antithyroid microsomal (antiMi) autoantibody (Ab) was found in synovial fluid (SF) before any clinical or serological evidence of thyroid disease. Subsequently, the follow-up of the two patients showed the appearance of thyroiditis within 2-5 years. The presence of anti-Mi Ab in SF might anticipate the appearance of autoimmune thyroiditis even in the absence of serum detectable antithyroid Ab, as was later observed in these two cases. PMID- 1914420 TI - Pigmented villonodular synovitis of the hip. A case report and review of the literature. AB - A 73-year-old patient, whose hip was completely destroyed by pigmented villonodular synovitis, was successfully treated by a total prosthetic replacement of this articulation. The etiopathogenesis of the illness is uncertain. Its' localization in the hip is, fortunately, a rare occurrence. It can be responsible for frequently extensive articular destruction which is even more dramatic when it affects young patients, whose average age is 35. Only early diagnosis permits conservative surgical treatment: total synovectomy associated with curettage of the foyers of osteolysis and their filling with bone grafts. If the destructive lesions are too extensive, an arthrodesis or replacement arthroplasty are proposed. PMID- 1914421 TI - Mixed sclerosing bone dystrophy with features resembling osteopoikilosis and osteopathia striata. AB - A 64-year old man, presenting pain in his back and left sciatalgia, was found to have a mixed sclerosing bone dystrophy with features resembling osteopoikilosis and osteopathia striata. Oval and round densities were found in the humeral heads, elbows, wrists, hands, pelvis, knees, feet. Striata densities were in the diaphyses of metacarpal and metatarsal bones. Bone scan was negative. Standard biochemical examinations of the blood and urine were negative. According to our investigations no evidence of osteopoikilosis other sclerosing bone dystrophies were found in the family of our patient. These data were discussed. PMID- 1914422 TI - Multicentric reticulohistiocytosis associated with subclinical Sjogren's syndrome. AB - A case of multicentric reticulohistiocytosis in a 60-year-old Japanese woman associated with subclinical Sjogren's syndrome is presented. The clinical features along with the light microscopic studies are commented. Partial improvement of the skin lesions and tendon sheath swelling was achieved after treatment with cyclophosphamide but the patient's general condition remained unchanged. Taking the rarity of multicentric reticulohistiocytosis into account, coexistence of these two conditions in the present and previously reported cases suggests that an autoimmune mechanism may play a part in the pathogenesis of multicentric reticulohistiocytosis. PMID- 1914423 TI - Long-term sequelae of pelvis irradiation: histological and microradiographical study of a femoral head. AB - Despite the lack of radiological signs, a femoral head showed histological and microradiographical features of osteonecrosis, 54 years after massive irradiation of the right hip. Intertrabecular spaces were invaded by connectivo-vascular tissue with focal accumulation of mast cells, and several resorption foci were filled with mononucleated cells. Moreover, all the microradiographs showed peculiar hypercalcified lines, sometimes containing empty osteocytic lacunae, the origin of which is difficult to precise. This study suggests that massive irradiation of weight-bearing epiphyses may be responsible for particularly long term hypovascularity, osteonecrosis and disturbed bone remodeling. PMID- 1914425 TI - Acute hepatitis due to ketoprofen. PMID- 1914424 TI - Histopathological findings in a case of systemic lupus erythematosus-associated anti-phospholipid syndrome. AB - The vessel anatomopathological lesions in a patient with systemic lupus erythematosus associated anti-phospholipid syndrome are described. Vasculitic lesions were nearly absent but small vessels showed hyalin thrombosis or substenosis due to subendothelial deposition of amorphous PAS-positive material in different anatomical districts. These findings can be related to the patient's clinical manifestations, particularly the central nervous system involvement and can be discussed regarding the possible pathogenetic mechanisms. PMID- 1914426 TI - Analgesic selection when the patient is allergic to codeine. PMID- 1914428 TI - Valproic acid hepatotoxicity in adults and older children. PMID- 1914427 TI - Dosage of antimycobacterial agents. PMID- 1914429 TI - Prediction of serum albumin concentration after albumin supplementation in pediatric patients receiving parenteral nutrition. PMID- 1914430 TI - A nonexponential, nonlogarithmic pharmacokinetic dosing method for gentamicin. PMID- 1914431 TI - Multiple-dose activate charcoal as adjunct therapy after chronic phenytoin intoxication. PMID- 1914432 TI - Criteria for use of ketorolac tromethamine in adult inpatients and outpatients. PMID- 1914433 TI - Aspects of sympathetic nervous system regulation in patients with cirrhosis: a 10 year experience. PMID- 1914434 TI - The effect of resistance training on blood pressure in normotensive women. AB - The purpose of the present study was to determine whether conventional resistance training alters 24-h ambulatory and manually determined casual blood pressure of normotensive women. Seven individuals (23 +/- 2 years old) trained 2 days week-1 for 20 weeks emphasizing the hip and knee extensor muscle groups. Three sets to exhaustion of the knee extension, squat, knee flexion and leg press exercises were performed. The load for each exercise represented approximately 80-85% of the one-repetition maximum. Average values for 24-h ambulatory blood pressure were not different (P greater than 0.05) pre- and post-training (systolic, 107 +/ 4 vs. 109 +/- 1 mmHg; diastolic, 73 +/- 2 vs. 71 +/- 2 mmHg). Ambulatory values over 8-h segments of the 24 h (day, evening, night) and casual resting determinations of blood pressure were also not affected. The lack of change in blood pressure cannot be explained by an insufficient training response. Knee extensor strength during dynamic or isokinetic actions increased (approximately 43%, P less than 0.05). In addition, biopsies from the vastus lateralis muscle showed an increase (P less than 0.05) in average muscle fibre cross-sectional area of 32%. This hypertrophic response was further substantiated by an increase (P less than 0.05) in lean body mass (41.2 +/- 1.3 kg to 43.4 +/- 1.5 kg). These results indicate that resistance training, which increases muscular strength, muscle fibre area and lean body mass, does not alter ambulatory or casual blood pressure. Thus, the concern that conventional resistance training may chronically elevate blood pressure does not appear warranted, at least in normotensive women. PMID- 1914435 TI - Transcutaneous oxygen tension measurements in the assessment of limb ischaemia. AB - The measurement of transcutaneous oxygen tension (TcPO2) has been adapted for the assessment of the blood supply of the lower limb. This study was undertaken to determine the most useful means of expressing TcPO2 measurements. We studied 176 patients with peripheral vascular disease and/or diabetes and 34 normal volunteers. Approximately++ half of the patients studied had ulceration or gangrene of the foot. A comparison of three methods of expressing TcPO2 measurement for predicting presence of ulceration was made using ROCA analysis. The absolute value of TcPO2 on the dorsum of the foot was the best predictor of the presence of ulceration or gangrene. An absolute value of TcPO2 of 30 mmHg on the dorsum of the foot had a sensitivity of 42% and specificity of 91%. The sensitivity of the test was as good in diabetic patients as in non-diabetic patients. PMID- 1914436 TI - Estimation of pulmonary vascular resistance in patients with ventricular septal defects by echo-Doppler cardiography. AB - The pulmonary vascular resistance is one of the parameters considered in the evaluation of patients with ventricular septal defects. We describe a new method to estimate resistance. The method estimates the systolic resistance in the pulmonary circulation and we assume that there is a linear relation between this resistance and the traditional resistance in which a continuous flow in systole and diastole is assumed. The systolic resistance was compared to the traditional resistance index in a group of patients whose invasive data were evaluated retrospectively. A close correlation between the two estimates of resistance was found and when the results were applied to another group of patients examined non invasively and invasively there was no significant difference between the invasive resistance index and the non-invasive estimate arrived at by the new method. PMID- 1914437 TI - Validation of body composition by dual energy X-ray absorptiometry (DEXA). AB - The present study validates the use of dual energy X-ray absorptiometry (DEXA) for measurement of body composition. The precision error was expressed as the SD (CV%) for fat mass, FAT%, lean tissue mass, and total body bone mineral: 1.1 kg (6.4%), 1.6% (5.7%), 1.4 kg (3.1%), and 0.03 kg (1.2%), respectively. The accuracy study in vitro used (1) mixtures of water and alcohol, (2) mixtures of ox muscle and lard, and (3) dried bones. In the clinically relevant range of values there were only small influences on DEXA measurements of variations in amount and composition of the soft tissue equivalents. The accuracy study in vivo compared the components of body composition measured recently by DEXA and earlier by dual photon absorptiometry, counting of naturally occurring total body 40K, and body density by underwater weighing in 25 healthy adult subjects. We found agreement between fat percentage (and lean body mass) by DEXA and the three established measurements modalities; mean differences were (-5.3 to -0.4%) and ( 0.7 to 2.5 kg) for fat percentage and lean body mass, respectively. We conclude that DEXA provides a new method of measuring body composition with precision and accuracy errors, which are compatible with the application of DEXA in group research studies and probably also in clinical measurements of the single subject. PMID- 1914439 TI - Preserved CO2 response in cerebral and muscular blood vessels during cimetidine treatment. AB - It is known that cimetidine inhibits the hypoxia-induced increase in cerebral blood flow (CFB) in dogs, but the mechanism of this inhibition is not fully understood. Since the accepted mechanisms explaining the increase in CBF during hypercapnia are very different from those active during hypoxia, acute hypercapnia was induced in 12 conscious dogs in order to study the cimetidine effect in this condition. Six dogs were given i.v. saline (control group) and the other six, i.v. cimetidine (4 mg kg-1). After 15 min, CBF and various muscular blood flow measurements were performed, using the microspheres technique under two conditions: (1) breathing air and (2) after 2 h inhalation of a gas mixture with FiCO2 0.10, FiO2 0.21 in nitrogen. The CBF increase was similar in both series with or without cimetidine. The changes in muscular blood flow were unaffected by the H2-blocker. We conclude that cimetidine has no effect on the CBF and on muscular blood flow during acute hypercapnia. PMID- 1914438 TI - Ambulatory measurement of nocturnal fluctuations in subcutaneous blood flow rate in the lower leg of man during 12-h periods with the portable CdTe(Cl) detector. Methodological considerations. AB - Possible sources of error during long-term measurements of subcutaneous blood flow rate with the portable CdTe(Cl) detector system were ruled out in the present study. Local blood flow rates were recorded in the lower legs of normal human subjects by means of the 133Xe wash-out technique. A good correlation was found between the portable CdTe(Cl) and stationary NaI(Tl) detector systems both prior to (r = 0.88, P less than 0.0001) and after (r = 0.68, P = 0.07) day over night (12 h) measurements. Identical post-ischaemic reactive hyperaemia could be demonstrated by both detector systems 12 h after the application of the isotope depot. This indicates that blood flow rates and vascular reactivity can be measured over 12 h by the portable CdTe(Cl) detector. Identical results were obtained during the 12-h measurements performed with the portable CdTe(Cl) detector attached directly to the skin surface and with the detector elevated above the skin surface. Therefore, geometrical changes were without any influence on our measurements. We conclude that measurements of subcutaneous blood flow rates in the lower leg of human subjects can be performed under out-patients conditions by means of the 133Xe wash-out technique and portable CdTe(Cl) detectors. A skin area greater than or equal to 4 cm should be labelled by means of the atraumatic, epicutaneous labelling technique and the detector attached directly to the skin surface with a single layer of a 20-micron thick gas-tight Mylar membrane interposed between the skin surface and the detector. The investigation of the subcutaneous blood flow rate should not be initiated until at least 90 min after labelling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914442 TI - The use of the walk test for the development of exercise guidelines. 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 field tests such as the one-mile-walk test. Health professionals often find it difficult to incorporate the results of such a field test in a format that can be used to advise individuals about how to start a safe and effective exercise program. This paper presents a computer program written in BASIC that determines an individual's maximal aerobic work capacity from a one-mile-walk test and establishes safe walk/jog guidelines that can be used to enhance physical fitness. Results are summarized in tabular as well as graphical format. This program, coupled with a new understanding of the benefits of exercise, allows for much more effective and precise exercise programs that will result in the improvement of the cardiovascular system and enhance the likelihood of long-term compliance. PMID- 1914441 TI - The forearm and leg perfusion techniques in man do not give the same metabolic information. AB - The present study evaluates whether forearm and leg perfusion techniques give the same metabolic information. Seven patients hospitalized for operation of uncomplicated disease were investigated pre-operatively in the fasted state, while seven other patients who were on intravenous nutrition were studied in the fed state. Blood flow and the extremity exchange of glucose, lactate, glycerol, free fatty acids and amino acids were measured simultaneously across the forearm and the leg in all individuals. In the fasted state the arteriovenous difference (a-v) of glucose uptake was statistically significant across the forearm while it was statistically insignificant across the leg (0.27 +/- 0.06 vs. -0.04 +/- 0.13 mmol l-1). The a-v differences of glycerol (0.025 +/- 0.028 vs. -0.043 +/- 0.013 mmol l-1) and free fatty acids 0.10 +/- 0.03 vs. -0.10 +/- 0.04 mmol l-1) were positive across the forearm while they were negative across the leg (P less than 0.01). In the fasted state the a-v difference of oxygen uptake (3.93 +/- 0.67 vs. 3.21 +/- 0.44 mmol l-1) and blood flow (4.1 +/- 1.0 vs. 4.0 +/- 0.7 ml min-1 100 g-1) did not differ between the arm and the leg, but the a-v difference in carbon dioxide production was significantly higher (P less than 0.05) across the forearm (2.43 +/- 0.37 vs. 1.29 +/- 0.29 mmol l-1) compared to the leg. In the fed state all the above-mentioned differences between forearm and leg became statistically insignificant. In the fed state the a-v difference of the sum of all amino acids was not significantly different from zero balance across the forearm (-146 +/- 103 mmol l-1) while there was a significant release from the leg (-175 +/- 6 mmol l-1, P less than 0.05). In the fed state the flux of the sum of all amino acids became significantly positive across the arm while it was not significantly different from zero balance across the leg. In the fed state, forearm blood flow was significantly higher than leg blood flow (6.2 +/- 0.5 vs. 4.0 +/- 0.2 ml min 1 100 g-1, P less than 0.001). The results in the present study demonstrate that the metabolic balance across regions of peripheral tissues may simultaneously differ considerably, i.e. being positive across the forearm and negative across the leg. This fact may imply that some previous claims may need reconsideration about 'peripheral tissue metabolism' associated with a certain clinical condition. PMID- 1914440 TI - Small accumulation of inosine monophosphate (IMP) despite high lactate levels in latissimus dorsi during transplantation. AB - The effects of prolonged ischaemia and subsequent reperfusion during and after reconstructive microsurgery on energy metabolism were studied. Repeated skeletal muscle biopsies were taken and analysed for high energy phosphates and their degradation products by high performance liquid chromatography and for lactate by a fluorometric procedure. Moderate changes in adenine nucleotides occurred during the first 4 h of ischaemia. After 6 h of ischaemia, when the creatine phosphate store was almost depleted and the lactate level had increased to 111 mmol kg-1 dry muscle, ATP content decreased and inosine monophosphate started to accumulate. The inosine monophosphate accumulation was however small, in spite of a high lactate level, which suggests that the increase in H+ associated with lactate formation is not important for the activation of AMP-deaminase during the present conditions. In spite of the accelerating metabolic deterioration during the later period of ischaemia, the reperfusion of the muscle resulted in a rapid normalization of all the studied metabolites, thereby indicating a rapid restoration of the muscle energy stores. PMID- 1914443 TI - A program to calculate the isoelectric point of macromolecules. AB - A program containing 260 sentences, written in BASIC and adapted to be run in personal computers, has been developed to calculate isoelectric point values of macromolecules (proteins, nucleic acids, polysaccharides, etc.). This implies the calculation of the coefficients and roots of a particular kind of polynomial. With common personal computers and using a compiled version of the program, the time required to calculate pI values of macromolecules containing for example, 9, 12, and 18 acid-base residues with different pK values was around 10 s, 2 min, and 2 h respectively. PMID- 1914444 TI - A basic program for calculation of APACHE II and Elebute scores and sepsis evaluation in intensive care medicine. AB - This paper describes a program for bedside-practicable calculation of APACHE II score, providing an additional option for both a rapid and sensitive screening as well as for a more specific sepsis assessment by the Elebute score in case of a putative diagnosis of sepsis. Thus, diagnostic and prognostic evaluation of septic patients and the assessment of disease progression and classification of "responders" to therapy can be promptly available in the ICU setting. The program is written in BASIC and therefore can easily be adapted to most microcomputers available on the market. PMID- 1914445 TI - A PC based computer program to aid the preparation of solvent systems for the HPLC. AB - An interactive computer program, SOLCOMP, is developed which calculates the volumes of the components that are to be added to obtain either a fresh solvent mixture or a new solvent system from the old one of required composition. The code is implemented in MicroSoft FORTRAN and GWBASIC which runs on any IBM compatible PC under MSDOS environment. PMID- 1914446 TI - Estimation of ED50 or LD50 using a programmable pocket calculator. AB - A program is developed for estimation of median effective dose (ED50 or LD50), using the hand-held programmable pocket calculator HP41CV. The well-known Finney's algorithm of probit analysis is used. Input of data is simple, but is restricted to a maximum of 15 groups. The program structure makes use of the technique of indirect addressing for storage, and statistical register manipulation for weighted regression. The ability of the calculator to give sufficiently precise results can be exploited in other similar situations. PMID- 1914447 TI - Computer image processing and automatic counting and measuring of fouling organisms. AB - The purpose of this study was to optimize the counting and measuring of marine fouling organisms on experimental panels using automated computer techniques. A script was developed that reduced the time required for the counting and measuring of marine fouling tubeworms by at least one order of magnitude over manual counts, with an error of five percent or less. Small, distinct tubeworms can be successfully counted by computer using a correction factor. Measurements of percentage cover or area should be made with larger tubeworms that have overlapping tubes. PMID- 1914448 TI - Computer analysis of physiologic signals in a cardiovascular research laboratory. AB - A comprehensive computer program which provides immediate computation and feedback has been developed for data acquisition and analysis of signals in a cardiovascular animal laboratory. The system is based on a microcomputer equipped with analog-to-digital converter and supports function modules which digitize, filter, and differentiate up to 8 simultaneously sampled cardiovascular signals. The program detects, analyses, and plots incoming and averaged beats. Beat-by beat signal averaging for each channel is performed and cardiac cycles are partitioned automatically. For each cardiac and average cycle the amplitude at 6 physiologic fiducial markers are measured and derived calculations are made. Channel vs channel plots and loop area measurements are also computed and displayed. The computer algorithms have been shown to give accurate, precise, and reproducible results when tested on canine cardiovascular data. Also, it has been demonstrated that signal averaging is an appropriate analysis technique for cardiovascular signals. PMID- 1914449 TI - A linear propagation model adapted to the study of fast perturbations in arterial hemodynamics. AB - The hemodynamic effect of rapid body accelerations is studied in this work using two different models of wave propagation in blood vessels. Simulation curves have been obtained with both models and compared with those measured in vivo on a dog's carotid artery. Results of the first model demonstrate that classic linear theories, based on linearization of the Navier-Stokes and continuity equations, provide a good explanation of the initial effect of body acceleration on pressure. However, the same models significantly underestimate the subsequent pressure perturbation damping. Modified empirical expressions for wave propagation, able to furnish a more accurate description of pressure energy losses occurring during fast hemodynamic phenomena, are thus utilized in the second model and their biophysical significance discussed. PMID- 1914450 TI - Mathematical model of electrotonic interactions during excitation and repolarisation of myocardial tissue. AB - A discrete model has been developed which reproduces the intercellular electrophysiological processes within a block of myocardial tissue. The behaviour of individual elements is introduced in the form of the digitised physiologic and premature action potentials which are comprehended as series of jumps between discrete polarisation levels. For each cellular element, the model introduces the excitation threshold as the minimum electric flow in the surrounding which can excite the cell, and the sensitivity towards the electronic interactions which can advance or slow down the depolarisation and repolarisation processes of the cell. The excitation threshold and the electronic sensitivity are dependent on the current polarity of the element. The numerical solution of the model does not use a fixed time slicing integration but is based on discrete planning of asynchronous events. The time increments are dynamically computed according to the chosen precision of the discrete polarity levels. The model enables efficient stimulation of the electrophysiological properties in three-dimensional models of the myocardial tissue. The paper presents a detailed formal description of the model. PMID- 1914451 TI - On the use of hidden Markov modelling for recognition of dysarthric speech. AB - Recognition of the speech of severely dysarthric individuals requires a technique which is robust to extraordinary conditions of high variability and very little training data. A hidden Markov model approach to isolated word recognition is used in an attempt to automatically model the enormous variability of the speech, while signal preprocessing measures and model modifications are employed to make better use of the existing data. Two findings are contrary to general experience with normal speech recognition. The first is that an ergodic model is found to outperform a standard left-to-right (Bakis) model structure. The second is that automated clipping of transitional acoustics in the speech is found to significantly enhance recognition. Experimental results using utterances of cerebral palsied persons with an array of articulatory abilities are presented. PMID- 1914452 TI - Strategies for graphical threshold determination. AB - Determining a threshold for a quantitative variable (arising in biological measurements for instance) is a common problem in medical decision making. We define seven commonly used strategies: each one leads to an optimal determination. To these strategies correspond relevant empirical curves: the ROC curve for strategies involving the sensitivity or the specificity, the predictive ROC curve (P-ROC curve) for strategies involving the positive and negative predicting values, and the well classified frequencies curve (WCF curve) for classification strategies where all misclassifications have the same importance. For one of the considered strategies, there also exists a theoretical formula for the optimal threshold, elicited within a classical probabilistic model, which gives a considerable advantage to this strategy. These strategies are applied to a stimulated example containing 702 cases, where we see that they lead to different optimal threshold values. Finally, we briefly review a practical application in the determination of thresholds for glycemia measurements, leading to the choice of one of them as the optimal one to consider in the gestational diabetes mellitus prediction. PMID- 1914453 TI - The assessment of bioequivalence in a two-period cross-over design: development of a simple BASIC program. AB - The complete algorithms needed in the calculation of confidence intervals on the basis of observations from a two-way cross-over bioequivalence trial are described. They do not contain assumptions as to the expected sampling distribution or possible period effects. The algorithms were used in a BASIC program, which was developed subsequently. Its validity is demonstrated here with a set of literature data. The program is available from the authors upon request. PMID- 1914454 TI - A system for compartmental modelling and simulation. AB - The paper describes a software package for modelling and simulating compartmental systems based upon a generalisation of the equations of compartmental systems. The aim is a versatile package which can be used for rapid model development. Its use is first illustrated in a number of simple classical examples. The power of the software--and more generally the methodology--is demonstrated by showing its application in developing a model-based system for insulin planning for diabetic patients. The software has been written in Pascal and runs on IBM PC and compatible computers. PMID- 1914455 TI - DTL: a language to assist cardiologists in improving classification algorithms. AB - Heuristic classifiers, e.g., for diagnostic classification of the electrocardiogram, can be very complex. The development and refinement of such classifiers is cumbersome and time-consuming. Generally, it requires a computer expert to implement the cardiologist's diagnostic reasoning into computer language. The average cardiologist, however, is not able to verify whether his intentions have been properly realized and perform as he hoped for. But also for the initiated, it often remains obscure how a particular result was reached by a complex classification program. An environment is presented which solves these problems. The environment consists of a language, DTL (Decision Tree Language), that allows cardiologists to express their classification algorithms in a way that is familiar to them, and an interpreter and translator for that language. The considerations in the design of DTL are described and the structure and capabilities of the interpreter and translator are discussed. PMID- 1914456 TI - Open prospective multicenter trial with a new monophasic contraceptive combination containing gestodene. AB - In a large and open prospective multicenter trial of 12,250 cycles from 2,378 women, contraceptive efficacy, clinical tolerance and acceptability of a new monophasic contraceptive combination containing 75 mcg gestodene (delta-5 levonorgestrel) and 30 mcg ethinyl oestradiol were studied. The objective was to assess efficacy, safety, side effects and cycle control of this oral contraceptive on healthy women using no other additional birth control methods. Two women became pregnant (0.016%) during the trial; both were patient failures. There was no effect on systolic or diastolic pressures. An average weight increase of 0.3 kg was noted. Cycle control was excellent with 95% of the cycles free of spotting and 98% free of breakthrough bleeding after six cycles. No serious complications occurred. There was an overall incidence of 14% reported side effects (after six cycles), indicating that the hormonal combination is well tolerated. It should be noted that 41.4% of the patients had some complaint before starting the treatment. For all complaints, a highly significant improvement was seen during the treatment. PMID- 1914457 TI - An open prospective study on the effects on carbohydrate metabolism of an oral monophasic contraceptive containing gestodene (WL-70). AB - The effects of a monophasic oral contraceptive (gestodene 75mcg + ethinylestradiol 30 mcg) on plasma glucose (PG) and insulin (IRI) responses to an oral glucose load (OGTT) and on glycosylated haemoglobin Alc (HbAlc), fructosamine (Fr), total cortisol (FT) and transcortin (CBG) were studied in 30 healthy women. Blood samples were taken before treatment and after 6 and 12 cycles. After 6 and 12 months, OGTT-PG and IRI levels showed substantially unchanged values; for HbAlc and Fr the same behaviour was seen with the exception of the latter between 6 and 12 months; FT and CBG showed significant rises. All recorded values were in the normal range. The basal and dynamic PG and IRI behaviour failed to show any significant variations between pre-treatment values and those after 6 and 12 months of OC administration. Other data showed a substantial neutrality for this oral contraceptive containing gestodene. PMID- 1914459 TI - Morphometric studies of the endometrium, the fallopian tube and the corpus luteum during contraception with the 300 micrograms norethisterone (NET) minipill. AB - Biopsy specimen from endometrium, Fallopian tube and corpus luteum were obtained from 35 women treated with 300 micrograms norethisterone daily and from 10 untreated, normally menstruating women. Peripheral levels of LH, progesterone and estradiol were measured. In the norethisterone-treated women four different ovarian reactions were identified. Ovarian activity was completely suppressed (Type A) in 3 women, follicular activity only (Type B) in 10 women, follicular activity was followed by insufficient luteal function (Type C) in 12 women, and peripheral estradiol and progesterone levels compatible with normal ovulation (Type D) in 10 women. The histology of the endometrium varied between atrophy (3 subjects), suppressed proliferation (9 subjects), proliferation (8 subjects), irregular secretory changes (12 subjects) and apparently normal secretory activity (3 subjects). When the histology of endometrium and Fallopian tube was compared with the peripheral hormonal levels and the corpus luteum steroid production in vitra, no correlation was found. Nor was a correlation found between the histologic changes of corpus luteum, endometrium and Fallopian tube. Thus, these target organs seem to react independently to norethisterone treatment. PMID- 1914458 TI - Effects of various IUDs on the composition of cervical mucus. AB - The influence of three different intrauterine devices on the composition of cervical mucus was studied. The amount of mucin, albumin and immunoglobulin G was estimated. After the insertion of an inert IUD, a decrease in mucin was observed. During copper-IUD use the content of mucin, albumin and IgG was increased in cervical mucus, while weight was not affected. In the levonorgestrel-IUD users, ovulation was inhibited in 2 out of 8 women. Mucus weight was increased. The amounts of mucin, albumin and IgG were not changed. In an in vitro experiment the effect of copper-IUDs on autooxidation of cholesterol was studied. There was an extensive conversion of cholesterol but addition of albumin quenched the oxidation of cholesterol. It is suggested that the increased secretion of albumin induced by copper-IUD users may offer protection against copper-induced cell damage. PMID- 1914460 TI - Sperm immobilizing effect of triterpene saponins from Acacia auriculiformis. AB - A mixture of two partially triterpenoid saponins (Tg), isolated from Acacia auriculiformis was tested for sperm immobilizing activity by using in vitro system. The lowest concentration (ED) required for an obvious immobilization of human sperm by using a modified Sander-Cramer test was found to be 0.35 mg/ml in physiological saline. The ability of the compound as a sperm immobilizing agent was compared with that of Triton X-100 and found to be more potent. Cervical mucus penetration test was also performed and the ED successfully prevented sperm entry in human cervical mucus. Supra-vital staining with eosin-nigrosin indicated death of the treated sperm. Electron microscopic study of Tg-treated sperm showed plasma membrane disintegration and dissolution of acrosomal cap which is presumably the cause for the spermicidal effect of the saponins. No permanent lesion was observed after application of 1.25 mg/ml Tg solution in physiological saline to the eye of rabbits for ten consecutive days. PMID- 1914461 TI - Antispermatogenic effects of tolnidamine in langur (Presbytis entellus). AB - Tolnidamine (50 mg/kg body weight; twice a week; oral) was administered for 90 days to adult male langur monkeys (Presbytis entellus entellus Dufresne) to assess its contraceptive potential. Semen weight, volume, seminal fluid volume, colour, pH and libido remained unchanged. Sperm motility, vitality and morphology were impaired with the advancement of treatment. Sperm density reduced to severe oligospermia following 75-90 days of treatment. Increased number of immature germ cells were also noticed. Resumption of changes to pretreatment range was observed following 90 days of cessation of treatment. However, sperm density remained low all through the recovery period of 150 days. Seminal fructose, ACP, LDH and citric acid concentrations did not change markedly. A significant depletion in GPC and magnesium levels was recorded during treatment and early recovery periods. Alterations in germ cells and Sertoli cells were also observed. A progressive but reversible rise in serum creatinine was evident. Other clinical parameters and body weight response revealed no drug-related alterations. In conclusion, tolnidamine medication induced irreversible inhibition of spermatogenesis. PMID- 1914462 TI - Pregnancy interceptive efficacy and biological profile of 3-amino-6,7-dimethoxy 1H-pyrazolo [3,4-b] quinoline (compound 85/83) in rodents. AB - Administration of compound 85/83 during the peri- and post-implantation period intercepted pregnancy in hamster and guinea pig by parenteral route and in hamster by oral route also. The m.e.d. for hamster and guinea pig was 10 and 20 mg/kg, respectively; lower doses were less effective. Restricting the administration to early post-implantation schedule interrupted pregnancy partially in both species. The compound was, however, ineffective in rat and in the pre-implantation schedule (days 1-4 post-coitum) in hamster. When tested in vitro on growing trophoblasts at 13.8 x 10(-5) M concentration, it prevented growth and caused degeneration of the cells within 24 h; lower concentration (9.2 x 10(-5) M) was less effective. The compound was found to be devoid of estrogenic, antiestrogenic, progestational and antiprogestational properties in conventional bioassays. In hormone competition assays, its relative binding affinity (RBA) to estrogen receptor was negligible (0.002% of estradiol-17 beta), while for uterine cytosol progesterone receptors in rabbit and hamster was 0.06 and 0.08% of progesterone, respectively. The compound 85/83 appears to intercept pregnancy by interfering with development of trophoblast cells. PMID- 1914463 TI - A proposed classification of changes in the electrocardiogram in acute myocardial infarction. AB - Concepts regarding the aetiology and significance of changes in the electrocardiogram in acute myocardial infarction (AMI) have been changing and modified substantially in recent years. Today, the electrocardiogram must be analysed in the light of our current knowledge. When interpreting it, one must consider all the new information that electrocardiography (including electrical field monitoring by means of body surface mapping) employing sophisticated technology can provide. Optimal electrocardiographic information and its classification in AMI require detailed evaluation of the electrocardiogram characterizing all alterations in waves, ST segment denivelizations as well as their combinations, distribution and duration. The authors propose a new classification of alterations in the electrocardiogram in AMI which takes into account also the dynamics of electrocardiographic alterations, formerly a standard parameter. Future research and, most importantly, clinical practice will show whether this electrocardiographic classification allows identification of relatively homogeneous (in terms of clinical status and prognosis) groups of patients with AMI. PMID- 1914464 TI - Value of signal averaged electrocardiogram for prediction of successful coronary artery thrombolysis. AB - In 60 patients with acute myocardial infarction (AMI) treated with brief i.v. infusion of streptokinase, signal averaged surface ECG as well as 24-hour ECG were recorded within the first 6 hours after admission and 5 to 10 days later. Results obtained from a group with presumed reperfusion (early plasma creatine kinase activity peak, cessation of pain, decrease in ST segment elevations, the appearance of "reperfusion arrhythmias"), were compared to those from patients with no reperfusion. The first recording showed a higher incidence of ventricular late potentials (VLP) in the group with reperfusion (77% vs. 44%, p less than 0.01), and a smaller difference in the incidence of complex ventricular arrhythmias (89% vs. 68%, p = 0.06). In the period between the two recordings, the incidence of VLP decreased in higher proportion in the same group (p less than 0.025). The incidence of complex ventricular arrhythmias was similar in both groups in the second recording. The authors conclude that complex ventricular arrhythmias following successful thrombolytic therapy occur together with "reperfusion VLPs", which are a better marker for successful thrombolysis in patients with AMI than a high grade of ventricular ectopic activity. PMID- 1914465 TI - Carotid and lower extremity arterial disease in acute myocardial infarction. AB - The authors present the results of noninvasive ultrasound examinations of the carotid and the arteries of the lower extremities in 111 patients with acute myocardial infarction. Carotid arterial disease was detected in 45 (41%). In 85% it was asymptomatic, haemodynamically significant lesions of the internal carotid artery were asymptomatic in more than half of the patients. Peripheral arterial disease was found in 43 patients (39%); it was bilateral in three fourths of them. Asymptomatic findings were present in 42%. Associated atherosclerotic lesions in both vascular locations were demonstrated in 16 patients (14%). On the average, patients with vascular changes had 3 risk factors and more. The most frequent risk factor was hypercholesterolaemia (79%) which was, at the same time, the most pronounced risk factor in patients with as well as without vascular changes. On the whole, peripheral vascular changes were found in 71 patients (64%) with acute myocardial infarction. PMID- 1914466 TI - Frequency and mechanism of daytime pulmonary hypertension in patients with obstructive sleep apnoea syndrome. AB - In order to study the frequency and the mechanisms of daytime pulmonary hypertension (PH) in obstructive sleep apnoea syndrome (OSAS) lung function tests, blood gas analysis and right-heart catheterization were performed in 46 consecutive patients. OSAS was assessed by polysomnography. 9 patients only (20%) had PH (mean pulmonary artery pressure (Ppa) greater than or equal to 20 mmHg). Patients with PH had lower daytime PaO2 (60.8 +/- 7.6 vs. 76.2 +/- 9.4 mmHg; p less than 0.001), higher daytime PaCO2 (44.8 +/- 4.2 vs. 38.0 +/- 4.0 mmHg; p less than 0.001), lower forced vital capacity (FVC) and forced expiratory volume (FEV1) (p less than 0.001), but the severity of OSAS was not different whether PH was present or not (apnoea index: 62 +/- 34 hour in the PH group vs. 65 +/- 40 hour, apnoea + hypopnoea index 102 +/- 33 hour in the PH group vs. 86 +/- 36 hour, lowest sleep SaO2: 59 +/- 21% in the PH group vs. 66 +/- 18%). There were significant correlations between Ppa and: daytime PaO2 (r = -0.61; p less than 0.001), PaCO2 (r = 0.55; p less than 0.001), FEV1 (r = -0.52; p less than 0.001) but not between Ppa and apnoea index, apnoea + hypopnoea index, lowest sleep SaO2. PH and daytime hypoxaemia were associated either with chronic airway obstruction or with severe obesity. PMID- 1914467 TI - A contribution to our understanding of post-implantation cross-section reduction in the vascular prostheses. AB - Using theory of linear elasticity, a theoretical model describing the decrease in the flow section of artificial vascular prostheses in response to blood pressure changes in proposed. The model is based on the presumably different deformation behaviours of the vessel and the prosthesis. An increase in the vascular intima thickness in small-calibre prostheses allows greater deformations of their inner surface, closely resembling those observed in the inner surface of the intimal layer of the normal vessel. Results of an analysis presented in the article show that depending on the material properties of the vascular prosthesis there exists such a critical radius of the prosthesis that smaller calibre prostheses, when used, become occluded. PMID- 1914468 TI - Passive geometric and elastic properties of human cadaver common carotid artery segments after intraluminal enzyme digestion with the aid of a four-way double balloon catheter. AB - A combined intraluminal nonenzymatic-enzymatic digestion procedure was carried out in situ on the common carotid arteries of 21 human cadavers with the aid of a four-way double balloon catheter. Denaturing pretreatment with NaOH, 2.5 mol for 20 min followed by crude pancreatic extract, 20 mg/ml for 20 min were used. Mechanical properties of cylindrical segments were measured in vitro, and compared with contralateral control segments. The inner radius increased and wall thickness decreased significantly at each pressure level in the 0-200 mmHg (0 26.7 kPa) intraluminal pressure range. Volume of wall material per unit length of the segment decreased by 11.6%, cross-section of the lumen at 100 mmHg (13.3 kPa) intraluminal pressure increased by 13.6%. These results show that the internal layers of human arteries can be removed by enzyme digestion increasing the lumen, while intact (medial and adventitial) layers still can give sufficient strength to the arterial wall. PMID- 1914469 TI - Ultrastructural changes in the endothelium of lung capillaries during experimental pneumonia. AB - In 35 guinea pigs a model of pneumonia was produced by transtracheal introduction of a sterile string. Electron microscopic study revealed that in the early stage of pneumonia (3-14 days after onset) endothelial cells in the capillaries of alveolar walls develop changes aimed at intensification of their function in sustaining an enhanced transcapillary gas exchange. In the following stage (1-4 months) endothelial cells develop progressing dystrophic changes leading to structural and functional disturbance of the blood-oxygen barrier. The dystrophic changes in endothelial cells develop later than those in alveolar epithelium. PMID- 1914470 TI - A comparative analysis of the spectrum of blood lipoproteins in random population samples. A Soviet-Polish cooperative lipid project. AB - Mean values of cholesterol contents in low- and high-density lipoproteins, and the 10% and 90% cut-off points of their distribution were determined in random samples of men aged 35-64 years and resident in three Soviet cities (Kiev, Moscow, Novosibirsk) and two Polish regions (Warsaw, and Tarnobrzeg province). Comparative analysis revealed that, while having identical mean total cholesterol levels, the studied populations differ both in the character of cholesterol distribution in atherogenic and nonatherogenic lipoproteins and in their age dynamics. The lipoprotein spectrum was also compared with data of overall mortality and that from ischaemic heart disease and stroke in the respective areas. The comparison suggested a potential association between the incidence of these diseases and the incidence of individual lipid risk factors in the population. The regional specifics of the blood lipoprotein spectrum must also be considered when developing programmes of atherosclerosis prevention. PMID- 1914471 TI - Atherosclerotic lesion of the circle of Willis: its study applying an atherometric system using multivariate statistical techniques. AB - In 2043 autopsies divided into the high (HAG) and low (LAG) atherosclerosis group a set of variables of a new atherometric system (AS) was used to characterize the atherosclerotic lesion (AL) in the circle of Willis arteries: fatty streaks (X), fibrous plaques (Y), severe plaques (Z), index of stenosis (P) and index of benignity (B). Principal component analysis identified a first component of severity (Y, P and Z) and a second component of benignity (X and B). Fibrous plaques play the main role in the severity of AL in the circle of Willis. The new AS proved its usefulness in characterizing the state of AL, whereas discriminant analysis and AS distinguished between the HAG and the LAG. The classification was correct in 74.5% and 76.5% when using three (X, Y, Z) and five (X, Y, Z, P, B) variables, respectively. PMID- 1914472 TI - Age-dependent changes in the level of antielastin antibodies of different immunoglobulin classes (IgG, IgM, IgA and IgD) in the human serum. AB - Serum samples from healthy subjects of different ages (within the age range 1-75 years) were tested for the presence of antielastin IgG, IgM, IgA and IgD by an enzyme-linked immunosorbent assay, utilizing insoluble human aortic elastin. All the tested sera showed detectable levels of antielastin antibodies of the four classes with the following regularities in changing their level with age. Antielastin IgG and IgM showed relatively high levels in the serum of children, growing even higher in the serum of subjects 18-20 years old. Then their levels were stabilized in the serum of 30-60 year olds for IgG and of subjects 30-50 years old for IgM and gradually decreased thereafter. The antielastin IgA showed non-significant changes with age up to the age of 40 and then its level gradually increased. The antielastin IgD showed statistically non-significant changes with age and a tendency to decrease after the age of 60. PMID- 1914473 TI - Comparative studies of systolic and diastolic function of the left ventricle in patients with dilated cardiomyopathy. AB - The main haemodynamic disturbance in dilated cardiomyopathy (DCM) is deterioration of systolic function of the left ventricle, while impairment of diastolic function demands more careful investigation. The purpose of the study was to analyse the relationship between the degree of dysfunction of the ventricle as a pump and diastolic dysfunction. During diastole, isovolumetric relaxation and myocardial compliance were assessed. Thirty nine patients with DCM underwent heart catheterization. The following results were obtained: an increase in LVMPD, LVEDP, LVESVI, LVEDVI and T; a decrease in EF, +dp/dt max, -dp/dt min, the (+dp/dt max)/(-dp/dt min) ratio was normal. There was a statistical correlation between: T and LVMDP (r = 0.79; p less than 0.001) and LVEDP (r = 0.67; p less than 0.001) as well as between LVEDVI and +dp/dt max (r = -0.67; p less than 0.001) and -dp/dt min (r = -0.64; p less than 0.001). It is concluded that in DCM: 1. the impairment of systolic and diastolic function progresses simultaneously, 2. disturbances in isovolumetric relaxation are dominant in relation to the filling phase deterioration. PMID- 1914474 TI - AaDO2 as a predictor of pulmonary hypertension resulting from pulmonary emboli. AB - The authors examined the records of all patients referred for right heart catheterization between 1963-84 because of persistent dyspnoea after one or more episodes of pulmonary emboli. Patients with a history of congestive heart failure, angina, restrictive or obstructive pulmonary disease that could explain their symptoms were excluded. Catheterization was performed 15.8 +/- 24 months after the first suspected episode of pulmonary embolism. Seven of the 29 patients included had resting pulmonary hypertension (PH). All of these had an alveolo arterial oxygen difference (AaDO2) greater than 25 mmHg. Twenty patients of the group, taken as a whole, had an AaDO2 greater than 25 mmHg. Information was available from 1 month to 5 years later in 6/9 patients with an AaDO2 less than 25 mmHg. In all of them dyspnoea improved or resolved. Information was available in 15/20 patients with AaDO2 greater than 25 mmHg. Three of 8 patients without PH but with an increased AaDO2 on the initial catheterization developed PH within 2 years. Dyspnoea increased in 1 of the remaining five. Four patients who initially had PH developed right heart failure 6 months-3 years later. In the remaining 3, dyspnoea was stable in 1, increased in 1 and one patient died with autopsy evidence of multiple pulmonary emboli. Abnormal oxygenation predicts the presence or subsequent development of PH in patients who are chronically dyspnoeic after pulmonary embolism. PMID- 1914475 TI - Surgical anatomy of the conduction system of the heart in anomalies of the membranous part of the ventricular septum with orifice in it. AB - Specific features of surgical anatomy of the atrioventricular conduction system (AVCS) in true and false aneurysms of the membranous part of the ventricular septum were studied on 126 heart specimens. The authors succeeded in localisation and dissection of the CS with the aid of an original method of anatomical microdissection which they prefer to the histologic method in studying the surgical anatomy of CS. The advantage of the authors' method consists in an objective anatomical identification of CS while preserving the integrity of adjacent structures. PMID- 1914476 TI - Thiamine cardiotropism. AB - Thiamine administration (200 mg/kg 2 hours before start of the experiment) substantially reduced the myocardial ischaemic lesion in a model of experimental myocardial infarction in the rat. As shown by stereometric analysis of histological heart preparations, the cytoprotective action of vitamin B1 is mediated by increased cardiomyocyte resistance towards ischaemia, i.e., through an adequate increase in the relative volume of the protection zone. Experiments on a model of emotional-painful stress in the rat show that the antiischaemic action of vitamin B1 cannot be explained by a specific cardiotropism of thiamine (the presence of thiamine phosphate buffer depots excludes the manifestation of coenzymatic effects of thiamine under given conditions) but by an antistressor action of thiamine resulting in exclusion of an important pathogenetic link in the mechanism of stress-conditioned cardiopathy. PMID- 1914477 TI - Gastric tonometry: an index of splanchnic tissue oxygenation? PMID- 1914478 TI - Gastric tonometry and venous oximetry in cardiac surgery patients. AB - OBJECTIVE: To determine the relationship between gastric intramucosal pH and several other indices of splanchnic perfusion in patients undergoing cardiopulmonary bypass. DESIGN: Prospective, single-arm study. SETTING: University Hospital. METHODS: Elective cardiac surgery patients (n = 8), free of hepatic disease, were studied. Before anesthetic induction, a triple-lumen, heparin-bonded fiberoptic catheter was inserted into the hepatic vein under fluoroscopic guidance. An identical catheter was inserted into the pulmonary artery. After endotracheal intubation, a nasogastric tube modified to permit measurement of gastric intramucosal pH was inserted into the stomach. Systemic oxygen delivery (DO2), and arterial, mixed venous, hepatic venous, and femoral venous blood gases and lactate concentrations were recorded at the following times: immediately before induction of anesthesia (time 1); during atrial cannulation (time 2); after 30 mins of hypothermic cardiopulmonary bypass (time 3); 15 mins after termination of cardiopulmonary bypass (time 4); and 1 hr after arrival in the ICU (time 5). Hepatic venous hemoglobin saturation (SO2) and mixed venous hemoglobin saturation (SvO2) were monitored continuously from times 1 to 5. Gastric intramucosal pH was recorded at times 2, 3, 4, and 5. The hepatic catheter was removed as soon as the last samples were collected in the ICU. RESULTS: The square of the weighted mean correlation coefficients (rw)2 for gastric intramucosal pH vs. hepatic venous lactate concentrations, gastric intramucosal pH vs. hepatic venous PO2, and gastric intramucosal pH vs. hepatic venous pH were (rw)2 = .50, (rw)2 = .58, and (rw)2 = .32, respectively. Systemic DO2, hepatic venous lactate concentrations, hepatic venous PO2, and hepatic venous pH were significant determinants in the multiple regression model for gastric intramucosal pH (r2 = .89). There were significant differences between SvO2 and hepatic venous SO2 at times 4 and 5. CONCLUSION: Gastric intramucosal pH may provide a minimally invasive way to monitor the adequacy of splanchnic DO2 in patients undergoing cardiopulmonary bypass. Additional data are necessary to determine whether low gastric intramucosal pH is truly a marker of supply dependent oxygen uptake across the hepatosplanchnic vascular bed under these conditions. PMID- 1914479 TI - Airway pressure release ventilation during acute lung injury: a prospective multicenter trial. AB - OBJECTIVE: To evaluate the feasibility of airway pressure release ventilation (APRV) in providing ventilatory support to patients with acute lung injury of diverse etiology and mild-to-moderate severity. DESIGN: Prospective, multicenter, nonrandomized crossover trial. SETTING: ICUs in six major referral hospitals. PATIENTS: Fifty adult patients with respiratory failure requiring mechanical ventilation and positive end-expiratory airway pressure. INTERVENTIONS: After optimization of continuous positive airway pressure (CPAP), conventional ventilation and APRV were administered sequentially for 30 mins. During APRV, the CPAP level and airway pressure release level were adjusted to prevent hypoxemia, while the degree of ventilatory support was adjusted by altering the frequency of pressure release. MEASUREMENTS AND MAIN RESULTS: Circulatory and ventilatory pressures, arterial blood gases and pH, heart rate, and respiratory rate were measured. Alveolar ventilation was augmented adequately in 47 of 50 patients by APRV. Adjustment of APRV required an increase in mean CPAP from 13 +/- 3 (SD) to 21 +/- 9 cm H2O and a release pressure of 6 +/- 5 cm H2O. This airway pressure pattern produced a mean airway pressure comparable to that pressure achieved during conventional ventilation. Failure of APRV in three patients could be attributed to an inadequate level of CPAP or an inadequate APRV rate. While maintaining oxygenation of arterial blood and circulatory function, APRV allowed a substantial (55 +/- 17%; p less than .0001) reduction in peak airway pressure compared with conventional positive pressure ventilation adjusted to deliver a comparable or lower level of ventilatory support. CONCLUSIONS: APRV is a feasible alternative to conventional mechanical ventilation for augmentation of alveolar ventilation in patients with acute lung injury of mild-to-moderate severity. PMID- 1914480 TI - Reduction of colonization and infection rate during pediatric intensive care by selective decontamination of the digestive tract. AB - OBJECTIVE: To compare the effects of two different antibiotic regimes on the colonization and infection rates of critically ill pediatric patients. DESIGN: A prospective randomized trial. SETTING: A pediatric ICU in a university hospital. PATIENTS: Fifty critically ill pediatric patients who required intensive care for at least 4 days were randomly allocated to either the selective parenteral and enteral antisepsis regimen (treatment group, n = 25) or the control group (n = 25). INTERVENTIONS: The treatment group received oral nonabsorbable antimicrobial agents (polymyxin E, gentamicin, and amphotericin B) and parenteral cefotaxime, whereas the control group received either perioperative antibiotic prophylaxis or antibiotic therapy according to clinical or microbiological evidence of infection. RESULTS: Both groups were comparable for age, body weight, sex, and severity of illness. Colonization with Gram-negative microorganisms and yeasts in the oropharynx, and digestive and respiratory tracts increased rapidly up to 52% in the control group, whereas there was no colonization with these microorganisms in the treatment group. The occurrence rates of acquired secondary infections in the control and treatment groups were 36% and 8%, respectively (p less than .025). There were no differences between groups in the duration of intensive care or mortality rate. CONCLUSION: Selective oropharyngeal and gastrointestinal decontamination combined with systemic cefotaxime application allows for a significant reduction of the colonization rate with Gram-negative bacteria and yeasts in critically ill pediatric patients undergoing prolonged intensive care. In addition, it significantly reduces the Gram-negative infection rate of the respiratory system. However, this therapeutic approach does not alter ICU length of stay or mortality rate. PMID- 1914481 TI - Hemodynamic instability after the initiation of extracorporeal membrane oxygenation: role of ionized calcium. AB - OBJECTIVES: To prospectively document the occurrence of ionized hypocalcemia in infants and children treated with extracorporeal membrane oxygenation (ECMO), to determine if the type of calcium salt (calcium chloride or gluconate) used in priming the ECMO circuit affected ionized calcium, to determine if ionized calcium concentrations correlate with total calcium, protein, albumin, or total magnesium values, and to determine if the hypotension usually observed after ECMO initiation correlates with low circulating ionized calcium concentrations. DESIGN: Prospective study. SETTING: Pediatric ICU and neonatal ICU. PATIENTS: Sixteen neonatal and three pediatric patients who were started on ECMO for cardiopulmonary support. INTERVENTIONS: The ECMO circuit was primed in a standardized manner, 100 mg of calcium gluconate was added in group 1 patients and 100 mg of calcium chloride was added in group 2 patients. MEASUREMENTS: Ionized calcium was measured from the circuit before initiation of ECMO and from the patient before, and then 5, 10, 15, 30, 60, 120, and 240 mins after initiation of ECMO. Total calcium and ionized calcium concentrations were measured simultaneously every 6 hrs. Serum total protein, albumin, magnesium, and ionized calcium values were measured from blood samples collected simultaneously twice daily. RESULTS: A significant decrease in the mean serum ionized calcium value occurred 5 mins after the initiation of ECMO in both groups, p less than .001. The ionized calcium value remained significantly decreased until 30 mins after the initiation of ECMO. There were no differences between the ionized calcium concentrations obtained during priming with calcium gluconate vs. those concentrations obtained with calcium chloride priming (p = .79). Throughout the course of ECMO, the serum ionized calcium concentrations ranged from 0.60 to 1.86 mmol/L. Poor correlations existed between circulating ionized calcium values and total calcium (r2 = .30), total protein (r2 = .20), albumin (r2 = .20), and magnesium concentrations (r2 = .10). There was a good correlation between the patients' BP and ionized calcium concentrations after bypass was initiated (r2 = .87). CONCLUSION: Our data demonstrate that ionized hypocalcemia is a frequent occurrence after the initiation of ECMO. Since there is a poor correlation between ionized calcium and total calcium, ionized calcium concentrations should be measured directly in these patients. PMID- 1914482 TI - Effect of associated injuries and blood volume replacement on death, rehabilitation needs, and disability in blunt traumatic brain injury. AB - OBJECTIVE: To examine the effects of associated injuries on death, disability, rehabilitation needs, and cost in patients with blunt traumatic brain injury. DESIGN: A retrospective case series analysis of 1,709 patients with blunt traumatic brain injury, or 37.2% of 4,590 consecutive blunt trauma patients, was combined with a prospective study of a subset of 202 of the 1,709 brain-injured patients obtained during the same time period with regard to need for rehabilitation services, residual disability, and costs at 1 yr after discharge from the acute trauma center. SETTING: A level I regional trauma center that is also the statewide neurotrauma and multiple trauma unit serving a population of more than 3 million persons. RESULTS: Contingency table analysis showed the Glasgow Coma Scale to be highly predictive (p less than .0001) of likelihood of mortality, need for postacute inpatient rehabilitation, or discharge home. Of the blunt traumatic brain injury patients, 40.4% (691) had an isolated brain injury and 59.6% (1,018) had brain plus at least one other systemic injury. The mortality rate of the isolated brain injury group was 11.1% compared with 21.8% in all brain plus systemic injury groups (p less than .0001). Spine, lung, visceral, pelvis, or extremity injuries in blunt traumatic brain injury all increased mortality rate to greater than 25% (all simultaneously significant, p less than .0001). Analysis of the interaction of brain injury (quantified by Glasgow Coma Scale) with blood replacement in the initial 24 hrs showed that at any Glasgow Coma Scale range, percent mortality increased as the volume of blood increased. Hypovolemic shock increased the mortality rate from 12.8% to 62.1% (p less than .0001). The need for postacute inpatient rehabilitation in survivors also increased as blood replacement increased, and shock increased the percent of patients requiring post-acute inpatient rehabilitation from 39.7% to 60.3%. In 202 consecutive surviving brain trauma patients followed for 1 yr, isolated brain injured patients with moderate brain injuries had a 4% need for posttrauma, postacute inpatient rehabilitation with a total cost per case of $12,489 compared with the brain plus extremity injury group, who had a 23% postacute inpatient rehabilitation rate and a total cost per case of $36,177 at 1 yr. With severe brain injury, isolated brain injury increased postacute inpatient rehabilitation to 29% and 1-yr cost to $59,274, but with the brain plus extremity injury group, postacute inpatient rehabilitation increased to 49% and cost to $84,950. CONCLUSIONS: In blunt traumatic brain injury, the addition of major visceral or extremity injuries, with need for blood replacement or shock, increases the risk of death, the need for rehabilitation, and the costs of disability. PMID- 1914483 TI - Acute physiology and chronic health evaluation (APACHE II) scoring in a cardiothoracic intensive care unit. AB - OBJECTIVE: To evaluate the predictive value of the Acute Physiology and Chronic Health Evaluation (APACHE II) scoring system in cardiothoracic surgical patients. DESIGN: Prospective survey with follow-up to hospital discharge. SETTING: A cardiothoracic surgical ICU in a tertiary referral center. PATIENTS: Eight hundred sixty-nine consecutive patients admitted to the ICU were entered into this study. Data on 12 patients were incomplete. Forty-three patients had nonsurgical diagnoses. Three patients had noncardiothoracic operations. These exclusions left 811 patients for analysis, and all results pertain to these 811 cardiothoracic surgical patients. INTERVENTIONS: Demographic and physiologic data relevant to the APACHE II score were collected on all patients and entered into a microcomputer database for analysis. MEASUREMENTS AND MAIN RESULTS: The following procedures were performed: 65% of patients had coronary artery bypass grafts; 23% had heart valve surgery; 5% had thoracic surgical procedures; and the remainder had a variety of cardiothoracic operations. The mean duration of ICU care was 2.3 days and the mean age was 57 yrs. The mean APACHE II score was 9.5 and the overall predicted risk of dying was 4.59%, with an actual ICU mortality rate of 4.56%. The relationship between the APACHE II score and mortality rate was linear and significant (p less than .001). Patients with an APACHE II score of less than 10 had a mortality rate of 0.93%. Only a score of greater than 30 was uniformly associated with death, and then only in one patient. A chronic disease history, emergency surgery, and a longer ICU stay were significant markers for mortality. CONCLUSIONS: There was a good relationship between the APACHE II score and mortality rate. Low APACHE II scores accurately predicted survival but only very high scores accurately predicted death. PMID- 1914484 TI - Cardiac output from carbon dioxide production and arterial and venous oximetry. AB - OBJECTIVE: To determine cardiac output from measurements of CO2 production (VCO2), and arterial (SaO2) and mixed venous (SvO2) oxygen saturations, using a modified Fick equation, in which cardiac output = VCO2/[k (SaO2 - SvO2)], where k represents a constant. DESIGN: A metabolic measurement cart was used to measure VCO2 and oxygen consumption (VO2) at 3-min intervals. SaO2 and SvO2 were measured via a pulse oximeter and a fiberoptic right heart catheter, respectively. The initial value of k for each study was determined from initial simultaneous measurements of thermodilution cardiac output, VCO2, SaO2, and SvO2 via the equation k = VCO2/[cardiac output (SaO2 - SvO2)]. The value of k was assumed to remain constant for the entire study period. Thereafter, cardiac outputs calculated from k and the measurements of VCO2, SaO2, and SvO2 were compared with the simultaneously obtained cardiac outputs determined by thermodilution. Similarly, cardiac outputs calculated from the traditional oxygen Fick equation, where cardiac output = VO2/[13.4 x hemoglobin (SaO2 - SvO2)], were compared with the simultaneously acquired cardiac outputs determined by thermodilution. SETTING: Surgical ICU in a Veterans Affairs Medical Center. PATIENTS: Seven postoperative patients, mechanically ventilated using the intermittent mandatory ventilation mode, were studied over a mean period of 4 hrs. RESULTS: Cardiac output (obtained from VCO2 and oximetry saturations) was closely related to thermodilution cardiac output: with linear regression showing r2 = .96 and standard error of the estimate = 0.59 L/min, n = 21; and, with bias and precision = 0.17 and 0.68 L/min, respectively. The traditional oxygen Fick cardiac output was also closely related to the thermodilution cardiac output (r2 = .81, standard error of the estimate = 1.46 L/min, n = 22; bias and precision = 0.31 and 1.46 L/min, respectively). CONCLUSION: The proposed method for calculating cardiac outputs solely from VCO2 and oximetry saturations yields results that correspond closely to thermodilution determined cardiac outputs. The method is simple and avoids the difficulties in the Fick method associated with accurate VO2 measurement. This approach may be suitable for continuous cardiac output monitoring in critically ill patients. PMID- 1914485 TI - Reduction of duration and cost of mechanical ventilation in an intensive care unit by use of a ventilatory management team. AB - OBJECTIVE: To test the hypothesis that a formal interdisciplinary team approach to managing ICU patients requiring mechanical ventilation enhances ICU efficiency. DESIGN: Retrospective review with cost-effectiveness analysis. SETTING: A 20-bed medical-surgical ICU in a 450-bed community referral teaching hospital with a critical care fellowship training program. PATIENTS: All patients requiring mechanical ventilation in the ICU were included, comparing patients admitted 1 yr before the inception of the ventilatory management team (group 1) with those patients admitted for 1 yr after the inception of the team (group 2). Group 1 included 198 patients with 206 episodes of mechanical ventilation and group 2 included 165 patients with 183 episodes of mechanical ventilation. INTERVENTION: A team consisting of an ICU attending physician, nurse, and respiratory therapist was formed to conduct rounds regularly and supervise the ventilatory management of ICU patients who were referred to the critical care service. MEASUREMENTS AND MAIN RESULTS: The two study groups were demographically comparable. However, there were significant reductions in resource use in group 2. The number of days on mechanical ventilation decreased (3.9 days per episode of mechanical ventilation [95% confidence interval 0.3 to 7.5 days]), as did days in the ICU (3.3 days per episode of mechanical ventilation [90% confidence interval 0.3 to 6.3 days]), numbers of arterial blood gases (23.2 per episode of mechanical ventilation; p less than .001), and number of indwelling arterial catheters (1 per episode of mechanical ventilation; p less than .001). The estimated cost savings from these reductions was $1,303 per episode of mechanical ventilation. CONCLUSION: We conclude that a ventilatory management team, or some component thereof, can significantly and safely expedite the process of "weaning" patients from mechanical ventilatory support in the ICU. PMID- 1914486 TI - Effects of hemorrhage and resuscitation on bacterial antigen-specific pulmonary plasma cell function. AB - BACKGROUND AND METHODS: Nosocomial pneumonia is frequent after hemorrhage and trauma, and often contributes to multiple organ system failure, morbidity, and mortality in this setting. Although the percentages and numbers of resting pulmonary B cells (clonal precursors) able to be stimulated to produce antibodies to bacterial antigens are markedly decreased after hemorrhage, the effects of hemorrhage on the pulmonary plasma cells actually producing antibody to bacterial antigens have not been examined. To investigate this question, mice were bled 30% blood volume, then resuscitated with the shed blood 1 hr later. At predetermined times after hemorrhage, the mice were intranasally immunized with liposomes containing the bacterial polysaccharide antigen levan (from Aerobacter levanicum). One week later, lung lavages were performed to measure bacterial antigen-specific secretory immunoglobulin A (sIgA) titers and the numbers of intraparenchymal pulmonary plasma cells producing antibody against the bacterial antigen were determined. RESULTS: Reduced numbers of pulmonary plasma cells producing antibody against the immunizing bacterial polysaccharide antigen were found between 1 and 14 days after blood loss, and titers of bacterial antigen specific secretory IgA were decreased for greater than 2 wks after hemorrhage. The importance of these abnormalities in pulmonary B-cell function was demonstrated by an increased susceptibility to Pseudomonas aeruginosa pneumonia in mice infected 4 days after hemorrhage, when bacterial antigen-specific pulmonary plasma cell numbers were at their lowest point. Resuscitated mice showed the same increased susceptibility to P. aeruginosa pneumonia as did hemorrhaged but unresuscitated animals. CONCLUSIONS: Hemorrhage, even if resuscitated, results in alterations in bacterial antigen-specific pulmonary B cell function and secretory IgA production that are profound, long lasting, and associated with increased susceptibility to infection at this mucosal surface. Because these effects on pulmonary B-cell function do not occur immediately after hemorrhage, immunization techniques able to enhance bacterial antigen-specific secretory IgA titers at pulmonary surfaces may be able to increase resistance to nosocomial pneumonia if administered shortly after injury and blood loss. PMID- 1914487 TI - Inhibition of thromboxane synthesis reduces endotoxin-induced right ventricular failure in sheep. AB - BACKGROUND AND METHODS: There is a marked decrease of the right ventricular ejection fraction after the administration of a bolus of endotoxin to sheep. This hemodynamic response may be the result of thromboxane-mediated pulmonary hypertension. Right ventricular function was studied in an ovine model after the administration of endotoxin (1 microgram/kg Escherichia coli) with and without pretreatment with OKY-046, a selective thromboxane synthetase inhibitor. RESULTS: OKY-046 attenuated the endotoxin-induced increase in pulmonary arterial pressure and prevented the early decreases in right ventricular ejection fraction and cardiac output. However, thromboxane synthetase inhibition failed to prevent endotoxin-induced hypoxemia. The marked increase in plasma thromboxane concentrations, which is usually seen after the administration of endotoxin, was prevented by pretreating the animals with OKY-046. On the other hand, increased plasma prostacyclin concentrations were observed in sheep treated with the thromboxane synthetase inhibitor. CONCLUSION: This series of experiments shows that the early endotoxin-induced decrease in right ventricular ejection fraction can be alleviated by the application of OKY-046. PMID- 1914488 TI - Measurement of alveolar ventilation and changes in deadspace by indirect calorimetry during mechanical ventilation: a laboratory and clinical validation. AB - OBJECTIVE: To validate the assessment of changes in alveolar ventilation and deadspace by indirect calorimetry. DESIGN: An open comparison of two methods using a criterion standard. METHODS: Simultaneous measurement of minute ventilation with a metabolic monitor and a pneumotachometer during controlled and synchronized intermittent mandatory ventilation in intensive care patients (n = 14). Measurement of a change in alveolar ventilation with three different tidal volume values in a single-compartment lung model using an added external deadspace. Alveolar ventilation and deadspace/tidal volume were calculated from Bohr's equation using end-tidal PCO2 for the alveolar PCO2 value. RESULTS: The mean differences between minute ventilation measured by a metabolic monitor and minute ventilation measured by a pneumotachometer during controlled and synchronized intermittent mandatory ventilation were -0.04 +/- 0.61 (SD) L and 0.01 +/- 0.85 L, respectively. No significant difference was observed between measurements at the endotracheal tube and the expiratory port of the ventilator. In studies using the lung model, the external deadspace represented 6% to 19% of the three tidal volume measurements. The mean difference between the actual and measured deadspace was 3 +/- 9 mL (8.2 +/- 4.7%), with a slightly, but not significantly, lower precision at the high tidal volume. CONCLUSIONS: Changes in alveolar ventilation and deadspace can be accurately measured by combined use of indirect calorimetry and end-tidal CO2 analysis. PMID- 1914489 TI - Tracheal damage following conventional and high-frequency ventilation at low and high humidity. AB - OBJECTIVES: To compare the degree of tracheobronchial damage in newborn lambs ventilated for 6 hrs with relative humidities of 30% or 90% and continuous positive airway pressure breathing, conventional mechanical ventilation of 25 and 60 breaths/min, or high frequency flow-interrupted ventilation at 600 breaths/min. BACKGROUND AND METHODS: Tracheobronchial damage secondary to mechanical ventilation remains a major iatrogenic lesion of the newborn despite substantial advances in both mechanical design and ventilatory techniques. A histologic scoring system was used to compare the damage noted in the tracheobronchial epithelium of newborn lambs after 6 hrs of conventional mechanical ventilation or high-frequency flow-interrupted ventilation at two relative humidities. Three groups of animals were ventilated for 6 hrs with an FIO2 of 0.21 at 36.0 degrees C and relative humidity of 90%. The first group received continuous positive airway pressure of 4 cm H2O, the second group received slow rate, conventional mechanical ventilation at 25 breaths/min, and the third group received fast rate, conventional mechanical ventilation at 60 breaths/min. Two other groups of animals were ventilated for 6 hrs with an FIO2 of 0.21 at 36.0 degrees C and relative humidity of 30%. The first group was ventilated with high-frequency flow-interrupted ventilation at 600 breaths/min and the second group with slow rate, conventional mechanical ventilation at 25 breaths/min. Two additional groups served as nonintubated controls; one group was killed immediately after sedation and the other group was killed after 6 hrs of sedation. RESULTS: The damage was mild but significantly different from controls when 90% humidity was used and there was no difference in the histology score between continuous positive airway pressure breathing and conventional mechanical ventilation at 25 or 60 breaths/min. Significant inflammation, erosion, necrosis, and blistering occurred with both conventional mechanical ventilation at 25 breaths/min and high-frequency flow-interrupted ventilation at 600 breaths/min when 30% humidity was used. The damage was only found 5 mm below the tip of the endotracheal tube and not at 3.5 cm beyond the endotrachea tube in the trachea nor in the right main bronchus. CONCLUSION: These data indicate that endotracheal intubation and mechanical ventilation, regardless of the method of ventilation, cause damage to the tracheal mucosa, but that poorly humidified inspired gases cause significantly greater damage. PMID- 1914490 TI - Role of exogenous growth hormone and insulin-like growth factor I in malnutrition and acute metabolic stress: a hypothesis. PMID- 1914491 TI - Acute pulmonary edema following pericardiocentesis for chronic cardiac tamponade secondary to trauma. PMID- 1914492 TI - Severe methemoglobinemia in a 3-week-old infant with a urinary tract infection. PMID- 1914493 TI - Ischemic damage to the trachea: lateral wall pressure versus intracuff pressure. PMID- 1914494 TI - Roles of UDP-glucuronosyltransferases in chemical carcinogenesis. AB - UDP-glucuronosyltransferases (UGT) play a major role in the elimination of nucleophilic metabolites of carcinogens, such as phenols and quinols of polycyclic aromatic hydrocarbons. In this way they prevent their further oxidation to electrophiles, which may react with DNA, RNA, and protein. They also inactivate carcinogenic, N-oxidized metabolites of aromatic amines. Furthermore, glucuronides may be stable transport forms of proximate carcinogens excreted via the biliary or urinary tract, thereby liberating the ultimate carcinogen at the target of carcinogenicity. Isozymes of the UGT enzyme superfamily that control the glucuronidation of metabolites of aromatic hydrocarbons and of N-oxidized aromatic amines have been identified in rats and humans. Phenol UGT appears to be coinduced with other drug-metabolizing enzymes via the Ah or dioxin receptor. This isozyme probably controls various proximate carcinogens and contributes to the persistently altered enzyme pattern, leading to the "toxin-resistance phenotype" at cancer prestages. Knowledge about UGTs in different species, their regulation, and their tissue distribution will improve the risk assessment of carcinogens. PMID- 1914495 TI - Local supercoil-stabilized DNA structures. AB - The DNA double helix exhibits local sequence-dependent polymorphism at the level of the single base pair and dinucleotide step. Curvature of the DNA molecule occurs in DNA regions with a specific type of nucleotide sequence periodicities. Negative supercoiling induces in vitro local nucleotide sequence-dependent DNA structures such as cruciforms, left-handed DNA, multistranded structures, etc. Techniques based on chemical probes have been proposed that make it possible to study DNA local structures in cells. Recent results suggest that the local DNA structures observed in vitro exist in the cell, but their occurrence and structural details are dependent on the DNA superhelical density in the cell and can be related to some cellular processes. PMID- 1914496 TI - Binding sites for human interleukin 1 alpha, gamma interferon and tumor necrosis factor on cultured fibroblasts of normal cornea and keratoconus. AB - Keratoconus, a bilateral corneal disease, is characterized by modifications in corneal shape and thinning of the stroma. From a biochemical point of view, a decrease in collagen content, probably due to the high collagenase activity, has been reported. Gamma Interferon (gamma-IFN), Tumor Necrosis Factor (TNF), and Interleukin 1 (IL1) are peptide regulatory factors involved in immunological responses, but they also play a role in the synthesis of collagen and prostaglandin E2 by fibroblasts. In these experiments, we have determined the number of membrane binding sites for gamma-IFN, TNF, and IL1, and the dissociation constant (Kd) for each radiolabelled ligand. All experiments were carried out on cultured corneal stromal cells. Data from normal human corneas and from keratoconus were compared. No differences were found concerning gamma-IFN and TNF binding sites between normal corneas and keratoconus, while fibroblasts from keratoconus proved to bear four fold more IL1 binding sites than normal fibroblasts, with similar Kd. PMID- 1914497 TI - Effects on the fetal rat eye of maternal benomyl exposure and protein malnutrition. AB - Benomyl, a benzimidazole fungicide, produced ocular and craniocerebral malformations in fetal rats when administered to the dams by gavage in a dose of 62.4 mg/kg of maternal body weight/day on days 7-21 of gestation. Ocular anomalies included retinal dysplasia, cataracts, microphthalmia, and anophthalmia. These anomalies occurred in 43.3% of fetuses exposed to benomyl and a normal protein diet but increased to 62.5% when benomyl administration was combined with a protein deficient (8% casein) diet. Microscopic examination of the malformed eyes revealed that the most common abnormality, retinal dysplasia, consisted of rosettes of retinal cells and retinal infolding. The majority of rosettes had a single layer and a limiting membrane. Rosettes with two or three layers were also observed, particularly in fetuses exposed both to protein deficiency and benomyl. Although anophthalmia was identified macroscopically in five fetuses, only a single instance of true anophthalmia was found microscopically. These data support the results of previous investigators that benomyl induces ocular malformation and that protein deficiency enhances the teratogenic effects of benomyl. The disorderly proliferation of retinal cells and rosette formation resembled the periventricular cell masses that accumulate in brains exposed to benomyl and certain other teratogenic agents. The anti-tubulin action of benomyl is known to impair microtubule formation and it may produce brain and ocular malformations by disruption of neuronal proliferation and migration. PMID- 1914499 TI - Preventive effect of isocitrate on glucocorticoid-induced cataract formation of developing chick embryo. AB - Glucocorticoid-induced cataract formation appears to proceed via oxidation or peroxidation steps possibly caused by multiple activities of glucocorticoid in the living system. Attempts were made to modify GC-induced metabolic changes and prevent cataract formation using intermediates of the citric acid cycle. The compounds were applied to the embryos at 3, 10 and 20 hr after the administration of hydrocortisone succinate sodium (HC:0.25 mumol/egg) to 15-day-old eggs. At 48 hr after HC treatment the lenses were classified and analyzed. Almost all lenses were classified as stage IV-V (greater than 94%). However, the application of sodium isocitrate (IC:15 mumol/egg) which was the most potent among several intermediates tested showed a significant preventive effect against cataract formation. The administration of IC prevented the decline of GSH, the elevations of LPO and reduced the marked elevation of glucose in the lens caused by HC. The IC treatment also diminished the elevation of LPO in blood and liver. The above effects by IC on HC-induced events may be due to the action of IC in preventing the early decline of hepatic GSH caused by HC. Possibly IC was utilized as an intermediate of the citric acid cycle and a substrate for isocitrate dehydrogenase in cytosol to modify GC-induced metabolic changes. PMID- 1914498 TI - Purification of the isoforms of tear specific prealbumin. AB - A chromatographic method for separating tear specific prealbumin (TSP) into six isoelectric forms is described. Size exclusion high performance liquid chromatography (SE-HPLC) was used to isolate TSP from whole tears, followed by chromatofocusing fast protein liquid chromatography (FPLC) of the SE-TSP fraction on a Mono P column. This yielded six fractions varying in isoelectric point (pI) between 5.3 and 4.6. Subsequent anion exchange FPLC (Mono Q column) allowed a slight further purification of each Mono P fraction and removed Polybuffer from the Mono P fractions. Isoelectric focusing (IEF) of the TSP isoforms verified that the heterogeneity was based on pI, and confirmed that the chromatofocusing separation was in many respects the same as an IEF separation. Purity of TSP isoforms was determined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), IEF, enzyme-linked immunosorbent assay (ELISA) and immunoblotting of samples separated by SDS-PAGE and IEF. Amino acid analysis and N-terminal amino acid sequencing revealed subtle differences between the TSP isoforms. The entire purification procedure was conducted both with and without the addition of reducing agents and protease inhibitors to tear samples and all buffers used in the purification process. Relatively little difference was seen in the TSP isoform profile under these two sets of conditions. However, the tendency of isolated TSP to aggregate and precipitate was dramatically decreased under reducing conditions, resulting in significantly higher protein recoveries. This chromatographic purification procedure provides a basis for further study of the nature of the heterogeneity of TSP and characterization of the properties of this protein. PMID- 1914500 TI - Development of actin polygonal arrays in rabbit lens epithelial cells. AB - In searching for a clue to the role of actin filament bundles organized into polygonal arrays, or geodomes, in lens epithelial cells, we examined several physical events occurring in the young rabbit lens which may initiate their formation. We used NZW rabbits between the ages of 24 days gestation and 50 days postnatal. Data were obtained from TEM, SEM and fluorescence microscopy. Parameters measured were lens weights, apical surface areas of cells in epithelial whole mounts, epithelial cell thickness, and timing of eyelid opening, breakdown of the tunica vasculosa lentis (TVL) and formation of the ciliary zonules; these findings were correlated with the first signs of development of the arrays. Polygonal arrays formed slowly beginning at one to two days after birth, and with advancing time these thickened and made more numerous connections with the lateral plasma membranes. Development of the arrays was not correlated with onset of vision or disappearance of the TVL or a sudden increase in cell area, since these events occur postnatally at about 9-10 days, nor with the development of zonular fibers since these are already in place at 24 days of gestation. Only lens weights showed a dramatic increase between 24 days gestation and birth. It is surmised that the expanding lens mass may be involved in some way in signaling the organization of actin filaments into geodomes. PMID- 1914501 TI - Quantitative evaluation of the corneal epithelial barrier: effect of artificial tears and preservatives. AB - The effect of artificial tear solutions on the corneal epithelial barrier was evaluated by measuring corneal uptake of 5, 6 carboxyfluorescein (CF) after exposure of rabbit corneas to various formulations in a conjunctival cup. Four tear solutions containing 0.01% benzalkonium chloride (BAC), a formulation containing 0.001% Polyquad, a contact lens re-wetting solution containing 0.004% thimerosal, and each of the above preservatives in balanced salt solution (BSS) were evaluated. Four non-preserved solutions were also tested. After treatment with the solutions corneas were exposed to the CF, removed from the eyes and dialyzed in balanced salt solution. The CF concentration in the dialysate was measured by fluorometry. Solutions containing 0.01% BAC caused a 9.24 to 99.28 fold increase in CF uptake as compared to control. Solutions preserved with Polyquad or thimerosal caused only a 0 to 4 fold increase in CF uptake while non preserved solutions caused no change compared to control. Corneas prepared for transmission electron microscopy using fixative containing ruthenium red exhibited damage which correlated well with CF uptake; the ruthenium red penetrated the epithelium to the basal cell layer after corneal exposure to solutions containing BAC while only superficial cell layers were stained after exposure to the other test solutions. The method used in this study allows statistical comparison of artificial tear formulations. The data show that patients with severe dry-eye who use artificial tears frequently should avoid tear solutions containing BAC and that non-preserved solutions are preferable for treatment of these patients. PMID- 1914503 TI - Retinal cryoapplication and fibrinolysis in experimental vitreous hemorrhage. AB - Retinal cryoapplication accelerates blood resorption of experimental vitreous hemorrhages shortening the time until fundus visualization is possible. For the animals that underwent cryoapplication five days after blood injection into the vitreous cavity, the mean time to fundus visualization was 3.75 weeks versus 5.06 weeks for the control group (p less than 0.001). Retinal cryoapplication also causes an increase in the concentration of fibrin degradation products in the vitreous cavity, indicating an activation of fibrinolysis, one of the most important processes involved in hemorrhage resolution. Use of topical indomethacin slightly lessens the effect of cryoapplication on acceleration of blood resorption (mean 4.06 weeks until visualization), but does not influence the effect on fibrinolysis. PMID- 1914502 TI - Cysteine protease inhibitor E64 reduces the rate of formation of selenite cataract in the whole animal. AB - The purpose of this experiment was to test the effectiveness of E64 in prevention of selenite nuclear cataract in the whole animal. E64 is an inhibitor of cysteine proteases such as calpain (EC.3.4.22.17). In the whole animal, daily intraperitoneal injection of E64 was mildly effective in slowing the rate of formation of selenite nuclear cataract, although prevention was not permanent. Frequency of the nuclear cataract in selenite group at 5 days post selenite injection was significantly decreased from 40% to 17% in the selenite + E64 group, and the density of cataract in the Se + E64 group was reduced. However, crystallins and calpain were still degraded in the selenite + E64 group. E64 was more effective against selenite cataract when present continuously during lens culture, where it slowed the rate of formation of nuclear opacity. Amelioration of cataract occurred both in vitro and in vivo even though lens calcium concentrations were elevated. The results supported the idea that application of calpain inhibitor is beneficial in prevention of rodent selenite cataracts. PMID- 1914504 TI - Suppression of VIP- and terbutaline stimulated aqueous humor flow by increased intraocular pressure in the cynomolgus monkey. AB - The effect of increased intraocular pressure (IOP) on stimulated aqueous humor flow (AHF) was studied in cynomolgus monkeys. Two experimental series were performed, one with unilateral VIP-treatment (60 micrograms intracamerally) and one with unilateral terbutaline-treatment (10 micrograms.ml-1 perfusion fluid). The AHF was determined with a labelled albumin dilution method, and an artificial increase in IOP was produced by clamping the outlet of the perfusion system, thus causing a net inflow of perfusion fluid. The initial AHF was significantly higher in the VIP-treated eye than in the control eye - 1.568 +/- 0.095 as compared to 1.112 +/- 0.103 microliters.min-1 (P less than or equal to 0.01). The spontaneous IOP was 5.8 +/- 0.4 mmHg (P less than or equal to 0.001) higher in the VIP treated eye. There was no difference in pseudofacility between the VIP-treated eye (0.063 +/- 0.016 microliter.min-1.mmHg-1) and the control eye (0.065 +/- 0.022 microliter.min-1.mmHg-1), but the total and true outflow facilities were higher in the VIP-treated eye. In the experiments with terbutaline, the initial AHF was 1.729 +/- 0.114 for the experimental eye and 1.262 +/- 0.104 microliters.min-1 for the control eye (P less than or equal to 0.01). The pseudofacility tended to be higher in the terbutaline-treated eye (0.072 +/- 0.026 microliters.min-1.mmHg-1) than in the control eye (0.048 +/- 0.012 microliters.min-1.mmHg-1), but the difference was not statistically significant. There was no difference in total and true outflow facility between the experimental and control eye. The results indicate that the pressure sensitivity of the AHF is independent of the initial level of the AHF. VIP increases true outflow facility, possibly via a direct effect on the trabecular meshwork. VIP also appears to rise the IOP due to an increase in episcleral venous pressure, which could be secondary to vasodilatation in the anterior segment. PMID- 1914505 TI - Detection and characterization of Ca(2+)-activated K+ channels in transformed cells of human non-pigmented ciliary epithelium. AB - Cell-attached and excised inside-out membrane patches were used to study single channel currents in a cell line derived from human non-pigmented ciliary epithelium. Most of the patches contained a Ca(2+)-dependent K+ channel with large unitary conductance (200 pS in symmetrical K+ solutions). Single channel current in cell-attached patches exposed to high K+ solution in the pipette showed a null potential of -36 mV. This value, which should yield an approximate estimation of cell membrane potential, was reversibly increased by -30 to -40 mV in the presence of Ca2+ ionophores. Tetraethylammonium up to 10 mM applied at the membrane cytoplasmic face had no effect on the channel. Addition of 1 mM BaCl2 to excised patches caused a voltage-dependent blockade of the channel. In the presence of barium the unit currents were not altered, but the channel remained closed for long periods of time and the open state probability decreased with depolarization. The possibility that this channel participates in regulation of transepithelial ciliary body secretion is discussed. PMID- 1914506 TI - Air/liquid corneal organ culture: a light microscopic study. AB - Air/liquid organ culture of tissues with stratified epithelial layers has been shown to encourage tight packing of cells and promote cellular differentiation. In this study human corneas cultured in a air/liquid environment were compared to paired, conventionally-cultured corneas to determine if the long-term morphology could be improved. Fourteen paired human corneas were cultured at 37 degrees C in covered culture dishes for 1 to 3 weeks. Air/liquid cultured corneas were placed epithelial-side up in a fixed position and culture medium was added to a level so that during rocking the corneal epithelia were intermittently exposed to air/liquid environments. Mate corneas were cultured using the conventional method. In this method corneas are fully submerged, epithelial-side down, in culture medium. After 3 weeks of culture significantly less epithelial intercellular edema was noted for the air/liquid cultures (p = 0.033), compared to conventional cultures. Significant improvements in cellular structure of the endothelial layers, after 1 and 3 weeks incubation (p = 0.029 and 0.000) and stromal layers, after 3 weeks in culture (p = 0.024), were also noted. We have shown that slight modifications of the organ culture environment lead to improvements in corneal morphology. Air/liquid corneal organ culture has promise for use in corneal wound healing studies and long-term culture. PMID- 1914507 TI - Relationship in humans between ascorbic acid consumption and levels of total and reduced ascorbic acid in lens, aqueous humor, and plasma. AB - The relationships between plasma, aqueous humor and lens ascorbic acid levels are examined in 131 samples from 127 patients. Mean ascorbate intake for nonsupplemented individuals was 148 mg/day or over two times the recommended daily allowance. A subset of 44 patients participated in a trial to assess the impact of vitamin C supplementation of 2 grams per day on aqueous and lens ascorbic acid levels. Such supplementation significantly increased both total and reduced ascorbic acid levels in plasma and aqueous and total ascorbic acid in the lens. Correlation coefficients relating total and reduced ascorbic acid levels in the three tissues ranged from 0.42 to 0.19 (p less than 0.05 for all correlation coefficients). Over 60% of the ascorbate was present in the reduced form in plasma and aqueous, and about 50% of the lens ascorbate was in the reduced form. PMID- 1914509 TI - The fate of antigen-antibody complexes in the rabbit cornea. AB - The mechanisms involved in the clearance of immune deposits in tissues are not yet clear. The cornea was chosen as a model to examine this question due to its avascularity and transparency. Bovine serum albumin (BSA) and rabbit anti BSA serum were injected at opposite sites into the corneal stroma of unsensitized rabbits. Within a day, a sharp opaque line was seen macroscopically between the two injection sites. Sections of the corneas were examined by light microscopy and electron microscopy; furthermore, immunohistochemical techniques were used. With the light microscope, a precipitation line was seen in the corneal stroma, which was identified as an antigen-antibody complex by immunofluorescence techniques. In the same area infiltrating polymorphonuclear cells and swollen keratocytes were observed. In the ultrathin sections precipitates were seen lying between the collagen fibrils without affecting the structure of the collagen. The swollen keratocytes had an activated rough endoplasmic reticulum. In certain cases the precipitates appeared to be intracellular, both in the polymorphonuclear cells, as well as in the keratocytes. These findings suggest that stromal keratocytes may play an important role in the degradation of corneal immune deposits. PMID- 1914508 TI - Production of latent transforming growth factor-beta and other inhibitory factors by cultured murine iris and ciliary body cells. AB - Aqueous humor contains transforming growth factor-beta (TGF-beta) and other inhibitory factors for cellular proliferation. In the present study we investigated the possibility that these factors are produced locally by cells found within the iris and ciliary body. Iris and ciliary body (I/CB) cells or whole tissue explants from C57BL/6 mice produced soluble factors which inhibited both murine thymocyte and mink lung epithelial cell proliferation. Indomethacin partially blocked inhibition of thymocyte proliferation, but did not affect inhibition of Mv1 Lu proliferation. The inhibitory activity of culture supernatants was not blocked by neutralizing antibodies to TGF-beta 1 or TGF-beta 2. However, following acid activation of culture supernatants from both I/CB and corneal tissue, increased inhibitory activity consistent with activation of latent TGB-beta was detected. Antibody neutralization experiments demonstrated that this increase in activity was due primarily to TGF-beta 2 for I/CB tissue. Polymerase chain reaction (PCR) analysis of cDNA generated from I/CB tissue mRNA showed prominent fragments representing both TGF-beta 1 and TGF-beta 2 mRNA. Corneal tissue, however, showed a prominent fragment for TGF-beta 1 mRNA, but either no band or a barely detectable fragment for TGF-beta 2 mRNA. Therefore, it remains uncertain whether TGF-beta 2 mRNA is produced by the cornea in this strain. Overall, these results demonstrated that three distinct categories of substances inhibitory to proliferation may be locally produced by resident iris and ciliary body cells: 1) indomethacin sensitive products, 2) TGF-beta 2 in latent form, and 3) factors not blocked by indomethacin or anti-TGF-beta neutralizing antibodies. Products generated by these tissues may have important regulatory properties in the development of immune responses to antigens introduced into the anterior chamber. PMID- 1914510 TI - Immunocytochemical study of phenobarbital- and 3-methylcholanthrene-inducible cytochrome P450 isozymes in primary cultures of porcine ciliary epithelium. AB - We found in the previous study that the induction of 7-pentoxyresorufin O dealkylase and 7-ethoxyresorufin O-dealkylase activities by phenobarbital and 3 methylcholanthrene, respectively, is more pronounced in porcine ciliary nonpigmented epithelial cells than in pigmented epithelial cells. In order to determine whether cytochrome P450 isozymes that mediate the O-dealkylase activities are also induced in nonpigmented cells under the conditions, primary cultures of porcine ciliary processes were treated with phenobarbital and 3 methylcholanthrene and the expression and localization of cytochrome P450 isozymes induced by these compounds were investigated by immunocytochemical methods using antibodies against the individual P450 isozymes. Intense labeling of nonpigmented epithelial cells was observed when ciliary processes treated with phenobarbital were reacted with anti-P450 (phenobarbital) antibody and when the processes treated with 3-methylcholanthrene were incubated with anti-P450 (methylcholanthrene) antibody. The labeling patterns supported the conclusion that the O-dealkylase activities and P450 isozymes specific for these activities are co-induced in and localized to the endoplasmic reticulum. This study is the first report presenting direct evidence of cytochrome P450 induction in primary cultures of ocular tissues and demonstrates the usefulness of porcine ciliary epithelial cells for studying the induction of ocular drug metabolizing enzymes. PMID- 1914511 TI - Trials of vaccination against experimental autoimmune uveoretinitis with a T-cell receptor peptide. AB - T lymphocytes which mediate several experimental autoimmune diseases, including encephalomyelitis (EAE) and uveoretinitis (EAU) in Lewis rats, preferentially utilize V beta 8 gene product in their receptor. Vaccination against a V beta 8.2 derived peptide was reported to inhibit EAE induction and we report here on the effect of vaccination with this peptide on the development of EAU. Experimental rats were pretreated with the V beta 8.2 peptide, emulsified in adjuvant (CFA), whereas control animals were untreated or injected with saline in CFA. Rats of all groups were immunized 30 or 40 days later with the immunopathogenic antigen, emulsified in Mycobacterium-enriched CFA. Vaccination with CFA emulsions containing either the V beta 8.2 peptide or saline, remarkably inhibited the development of the tested diseases, as compared to the untreated controls. Vaccination with the V beta 8.2 peptide had variable effects in this study on disease development: it inhibited the S-antigen-induced EAU more than did treatment with CFA in four out of six experiments, had a similar effect to that of CFA in one experiment and enhanced the disease in another experiment. Conversely, vaccination with the V beta 8.2 peptide slightly enhanced the EAU induced by the interphotoreceptor retinoid-binding protein (IRBP), or its dominant determinant, in three of four experiments and had no apparent effect in the fourth experiment. In addition, we could not reproduce the reported protective effect of vaccination with the V beta 8.2 peptide against induction of EAE. Vaccination with the V beta 8.2 peptide also had no clear effect on the development of humoral or cellular immune responses against S-antigen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914512 TI - The heart as a target organ of immune injury. AB - Over the last 10 years, our knowledge of immunologically mediated processes involving the myocardium appears to have made quantum leaps. New and important disease entities such as AIDS have appeared and the cardiologist now becomes an important member of the "AIDS team." Our understanding of "older diseases" such as sarcoidosis, Lyme disease, systemic lupus and other connective tissue syndromes has significantly increased. The concept of high-dose steroid therapy for these processes may, in fact, turn out to be futile and more selective, as less dangerous immunosuppression is being introduced. This concept has significantly advanced in the field of cardiac transplantation where immunosuppression has now been usurped by specific immunotherapy aimed at selective aspects of the immune sequence. New and exciting concepts will emerge from the molecular biology laboratory that will have direct bearing on the management of patients with cardiovascular disorders. This information explosion will force the cardiovascular physician to become more in tune with the world of immunology and molecular biology. Many obvious, significant problems remain, such as accelerated atherosclerosis in the transplant patient and the role of myocarditis in the patient with heart failure. However, it will truly be an exciting decade in which to work and watch the unraveling of these mysteries and hopefully, the study of today's problems will give way to solutions and a clearer understanding of the heart as a target of immune injury. PMID- 1914513 TI - Autoimmunity: present-day concepts and future prospects. PMID- 1914514 TI - Thymic nurse cells: a site for positive selection and differentiation of T cells. PMID- 1914515 TI - Oligonucleotide-primed in situ DNA synthesis (PRINS): a method for chromosome mapping, banding, and investigation of sequence organization. AB - Oligonucleotides were annealed to complementary sequences in fixed human metaphase chromosomes and extended with DNA polymerase. The newly synthesized fragments were labeled by incorporating bio-11-dUTP instead of TTP, and the sites of synthesis were detected by immunocytochemistry, using fluorochromes as the reporter molecules. We have obtained clear localization with oligonucleotides from alphoid (centromeric sequences), simple sequence (satellite) DNAs, a variety of Alu-dispersed repeated sequences, and oligonucleotides derived from the Tetrahymena and Trypanosoma telomere-specific sequences. The simple sequence and alphoid oligonucleotides gave results at least comparable to those obtained using the whole molecule as a probe for in situ hybridization, whereas the Alu oligonucleotides produced a diversity of results which depended on the absolute length and location of the oligonucleotide within the Alu sequence. The telomere specific oligomers also produced a variety of results. The G-rich Trypanosoma oligomer and its complementary C-rich sequence produced strong telomeric signals and some interstitial signals on mouse chromosomes, but only weak telomeric signals on human chromosomes. The G-rich Tetrahymena oligomer produced detectable telomeric signals on human chromosomes. The technique appears to be a valuable extension of present tools for mapping and examining the organization of DNA sequences within chromosomes. PMID- 1914516 TI - Assignment of human porphobilinogen deaminase to 11q24.1----q24.2 by in situ hybridization and gene dosage studies. AB - In situ hybridization and gene dosage-effect studies were conducted to determine the detailed chromosomal location of the gene encoding human porphobilinogen deaminase (PBGD). Red cell PBGD activity was normal in one patient with monosomy for 11q24.2----qter but was increased 1.5 times in another patient with trisomy for 11q22.2----qter. The cDNA probe for PBGD was found to be specifically hybridized to band 11q24. These results suggest that the gene for PBGD is localized within the region 11q24.1----q24.2. PMID- 1914517 TI - Mapping of the MYC gene to band 8q24.12----q24.13 by R-banding and distal to fra(8)(q24.11), FRA8E, by fluorescence in situ hybridization. AB - The MYC gene was mapped to R-banded human prometaphase chromosomes and to chromosomes expressing fra(8)(q24.11) by fluorescence in situ hybridization. By high-resolution banding analysis, the fluorescent signals were localized to R positive band q24.12----q24.13 of the long arm of chromosome 8. Furthermore, the signals were localized near the middle part, q24.12----q24.13, of the distal portion of fra(8)(q24.11) expression. Thus, the precise localization of MYC was to the subband 8q24.12----q24.13. PMID- 1914518 TI - In situ hybridization of two markers closely flanking the spinal muscular atrophy gene to 5q12----q13.3. AB - In order to refine the physical location of the p105-153Ra and M4 probes which closely flank the spinal muscular atrophy gene (SMA) on human chromosome 5q, in situ hybridization has been carried out on prometaphase chromosomes. Our results demonstrate that the disease gene is located between the 5q12----q13.1 and 5q13.3 bands. The present study will hopefully contribute to microdissection of the chromosomal region of the SMA gene. PMID- 1914519 TI - Rapid localization of membrane skeletal protein 4.1 (EL1) to human chromosome 1p33----p34.2 by nonradioactive in situ hybridization. AB - Hereditary elliptocytosis (HE) is a heterogeneous group of red-cell disorders. One class of HE patients was shown to have a mutated erythrocyte membrane skeletal protein 4.1 gene. We have recently shown that human protein 4.1 contains multiple isoforms with novel sizes, functions, and tissue-specific expression. Here, we report the subregional localization of this gene to human chromosome 1p33----p34.2, based on the fractional length, by nonradioactive in situ hybridization. PMID- 1914520 TI - Assignment of the fucosidase pseudogene FUCA1P to chromosome region 2q31----q32. AB - FUCA1P is a pseudogene of the structural fucosidase gene FUCA1. The former has been mapped to human chromosome 2, whereas the latter has been localized to chromosome 1p34----p36. We have further localized FUCA1P to chromosomal band 2q31 ---q32 by fluorescent in situ hybridization and digital imaging microscopy. This localization was confirmed by linkage analysis between FUCA1P and the COL3A1 gene in 2q24----q32 which gave maximal lod scores of 4.03 at 3% recombination. PMID- 1914521 TI - Chromosomal assignments of 23 biochemical loci of the rat by using rat x mouse somatic cell hybrids. AB - A panel of 18 rat x mouse somatic cell hybrid clones segregating individual rat chromosomes in different combinations was used to assign 23 biochemical loci to rat chromosomes. The chromosomal locations for these 23 loci were determined as follows: GOT1 on rat chromosome 1; HAGH on 2; ACP2, ADA, GANC, ITPA, and SORD on 3; LDHB on 4; PEPB on 7; GLB1 and HEXA on 8; IDH1 on 9; UMPH2 on 10; GUSB on 12; FH and PEPC on 13; PEPS on 14; ESD and NP on 15; DIA4 on 19; and PP on 20. In addition, ACP1 and GLO1 were reassigned to rat chromosomes 6 and 20, respectively. The chromosomal assignments of these loci extends the known syntenic homologies among rats, mice, and humans. PMID- 1914523 TI - Chromosome studies in the red howler monkey, Alouatta seniculus stramineus (Platyrrhini, Primates): description of an X1X2Y1Y2/X1X1X2X2 sex-chromosome system and karyological comparisons with other subspecies. AB - In the red howler monkey, Alouatta seniculus stramineus (2n = 47, 48, or 49), variations in diploid chromosome number are due to different numbers of microchromosomes. Males exhibit a Y;autosome translocation involving the short arm of an individual biarmed autosome. Consequently, the sex-chromosome constitution in the male is X1X2Y1Y2, with X1 representing the original X chromosome, X2 the biarmed autosome (No. 7), Y1 the Y;7p translocation product, and Y2 the acrocentric homolog of 7q. In the first meiotic division, a quadrivalent with a chain configuration can be observed in spermatocytes. Females have an X1X1X2X2 sex-chromosome constitution. Chromosome heteromorphisms were observed in pair 13, due to a pericentric inversion, and pair 19, due to the presence of constitutive heterochromatin. Microchromosomes, which varied in number between individuals, were also heterochromatic. NOR-staining was observed at two separate sites on a single chromosome pair (No. 10). A comparison of A.s. stramineus with A.s. macconnelli shows that these two subspecies have identical diploid chromosome numbers (47, 48, or 49), again due to a varying number of microchromosomes, and that they share a similar sex-chromosome constitution. Their karyotypes, however, are not identical, but can be derived from each other by a reciprocal translocation. Further comparisons with other A. seniculus subspecies reported in the literature indicate that this taxon is not karyologically uniform and that substantial chromosome shuffling has occurred between populations that have been considered to be subspecies by taxonomic criteria based on their morphometric attributes. PMID- 1914522 TI - The most frequently lost allelic site in human renal cell carcinoma (D3F15S2) on the short arm of chromosome 3 has homologous sequences on rat chromosome 8. AB - It has previously been shown that human chromosome 3 has banding homology to rat chromosome 8. We have previously isolated a cDNA from the D3F15S2 region and designated the gene as RIK. In the present study, we localized the homolog of this gene to rat chromosome 8. PMID- 1914524 TI - Second international workshop on human chromosome 17. PMID- 1914525 TI - Longitudinal differentiation of the human Yq heterochromatin as revealed by the restriction enzyme TaqI. AB - The restriction endonuclease TaqI cleaves DNA at TCGA sites which are very common in human satellite DNAs. However, this enzyme was not used successfully up to now to digest constitutive heterochromatin of human chromosomes, where those highly repetitive DNAs are preferentially located. In this work, we show that TaqI is able to cut and extract DNA from the major heterochromatic regions on chromosomes 1, 9, 15, and 16 which appear as unstained gaps. Yq heterochromatin displays moderate digestion along its entire length but a middle region can be distinguished which is usually more affected. Complete digestion of Yq heterochromatin can be achieved when this block has been previously undercondensed by treating cell cultures with the cytidine analog, 5-azacytidine. Thus, it may be deduced that some factors related to chromatin organization might be involved in the action of TaqI. These results come to reinforce previous data about heterogeneity of Yq heterochromatin, and allow us to subdivide it into three different regions according to their differential response to TaqI digestion. PMID- 1914526 TI - Visualization of R-bands in human metaphase chromosomes by the restriction endonuclease MseI. AB - Human metaphase chromosomes were treated with the restriction endonuclease MseI, which cuts DNA at TTAA sequences. This enzyme preferentially cuts and extracts DNA from G-bands and thus is the first restriction endonuclease allowing direct R band visualization. Specific patterns ranging from R+C-like to C-like banding can be induced, depending on the concentration of the enzyme. At intermediate concentrations, only a subset of R-bands are produced, corresponding to GC-rich bands that are especially resistant to heat denaturation (so-called T-bands). These results suggest that compositional differences between chromosomal regions determine the different rates of cleavage by MseI, not only between R- and G bands but also among different R-bands. PMID- 1914528 TI - Chromosome condensation from prophase to late metaphase: relationship to chromosome bands and their replication time. AB - As chromosomes condense during early mitosis, their subbands fuse in a highly coordinated fashion. Subband fusion occurs when two large subbands flanking one minor subband come together to form one band, which takes on the cytological characteristics of the original flanking subbands. Using four different banding techniques--GTG (G-bands obtained with trypsin and Giemsa), GBG (G-bands obtained with BrdU and Giemsa), RHG (R-bands obtained by heating and Giemsa), and RBG (R bands obtained with BrdU and Giemsa)--we studied subband fusion from prophase (1,250 bands per haploid set) to late metaphase (300 bands). To quantify the condensation process, a fusion index was established. We found that chromosomes contain preferential zones of condensation. From prophase to late metaphase, the early replicating subbands (R-subbands) fuse more readily with each other than do the late-replicating subbands (G-subbands). R-bands usually replicate early and condense late independently of the adjacent G-bands, which replicate late but condense early. Therefore, chromosome bands can undergo DNA replication and chromatin condensation relatively autonomously. Our data suggest that (1) chromosome replication and condensation are closely connected in time, (2) the metaphase bands represent independent units of chromatin condensation, and (3) the condensation process is an important feature of chromosome organization. PMID- 1914527 TI - Isolation and regional localization of 25 anonymous DNA probes on a chromosome 13 hybrid panel. AB - Clones were isolated from two flow-sorted chromosome 13 libraries. Twenty-five clones were localized to various regions of chromosome 13, using a well characterized panel of rodent x human hybrid cell lines. Eight DNA markers were localized to 13q14.2----q22, where the gene for Wilson disease, a recessive disorder of copper metabolism, was previously assigned. The new markers will be useful for the diagnosis of presymptomatic sibs of Wilson disease patients. We isolated six DNA clones proximal to the retinoblastoma gene, a region in which a translocation associated with rhabdomyosarcoma has been observed. Probes for both of these regions will be useful for the cloning of the genes involved in these diseases. PMID- 1914529 TI - Rationales for drug development in inflammation: eicosanoids and oxygen-derived free radicals. PMID- 1914530 TI - Nuclear volume in transitional cell tumours. An assessment of its prognostic and biological impact. PMID- 1914531 TI - Assessment of the physiological bone loss in women, with special emphasis on the menopausal changes. PMID- 1914532 TI - Towards early excision and extended grafting of excessive burns. PMID- 1914533 TI - Subcutaneous absorption of insulin in insulin-dependent diabetic patients. Influence of species, physico-chemical properties of insulin and physiological factors. AB - One major problem encountered when treating diabetic patients with insulin is the very large inter- and intra-individual variability in subcutaneous insulin absorption, a major contributory factor in the variability of the blood glucose level. Thus, to optimize insulin treatment the factors influencing the absorption have to be known and possibly utilized. The different types of insulin ("short acting", "intermediate-acting" and "long-acting") have different times of action. "Short-acting" and "intermediate-acting" human insulin are probably absorbed slightly faster than porcine (and bovine) insulin. "Long-acting" human insulin is absorbed significantly faster than bovine insulin. More concentrated "short acting" insulin (100 IU/ml) is absorbed slightly slower than less concentrated insulins (40 IU/ml). The absorption of "intermediate-acting" and "long-acting" insulin is dose-dependent, with a decreasing absorption rate with increasing dose of insulin. Insulin is administered subcutaneously either by injection or by using an infusion pump. The injection technique influences the absorption rate. Giving a continuous subcutaneous insulin infusion as a basal rate infusion, a depot is built-up. The building-up and the size of the depot, as well as the blood glucose and plasma insulin levels during steady-state conditions, are independent of the pulse-rate interval of the pump used (5 min vs 1 h). The size of the steady-state depot is constant during constant conditions but inversely correlated to the local subcutaneous blood flow and directly correlated to the infusion rate. An increase or decrease in the infusion rate during a basal rate infusion will after a delay of 2-3 h induce corresponding changes in the insulin absorption rate from the depot. After termination of the infusion, the insulin depot will still provide some insulin supply for 2-3 h. During the continuous infusion, the pharmacokinetics of the superimposed preprandial boluses will resemble injections of soluble insulin. The inter- and intra-individual variability in the insulin absorption, even when giving the same type, species, concentration and dose of insulin, is presumably primarily due to different and changing diffusion conditions in the subcutaneous tissue. Some factors which influence the diffusion conditions include exercise, local massage and, especially, local subcutaneous blood flow. Alterations in the blood flow induce, with a hyperbolic relationship, changes in the same direction in the absorption rate of injected and infused "short-acting" insulin and of injected "intermediate acting" insulin. Several factors have been shown to influence both subcutaneous blood flow and insulin absorption, e.g. injection site, skinfold thickness, smoking, orthostatic changes, ketosis and ambient temperature.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1914534 TI - The effects of general anaesthesia on antroduodenal motility, gastric pH and gastric emptying in man. AB - This survey was based on five recently published papers. The aims of the studies were to to investigate the effect of general anaesthesia on antroduodenal motility, gastric pH and gastric emptying. Antroduodenal motility was measured by manometry, gastric pH by a stomach microelectrode and gastric emptying rate using paracetamol absorption as an index. Two studies deal with antroduodenal motility during basal conditions and after administration of paracetamol and diazepam in 11 healthy volunteers. Three studies deal with the effects of 4 different methods of general anaesthesia on antroduodenal motility, gastric pH and gastric emptying rate in 43 patients undergoing orthopedic or plastic surgery not involving the abdomen having four different methods of general anaesthesia. In the healthy volunteers a close connection between antral activity and gastric emptying rate was found. Paracetamol had no effects on gastric pH. The changes in motility (a shortening of phase III and a decline in the incidence of antral phase III activity) were minor and ascribed to diurnal variations and by a possible stimulation of antral activity by the positioning of the manometric tube. It was found that no paracetamol was absorbed in the quiescent phase I, irrespective of its duration, and that the absorption rate of paracetamol correlated with the duration of phase II and the occurrence of antral activity during phases II and III. The effects of premedication with diazepam on antroduodenal motility, gastric pH and gastric emptying rate was investigated in the same healthy volunteers prior to the patient studies. Also in this study a correlation between antral activity and gastric emptying rate was found. Furthermore, it was observed that some volunteers had fast gastric emptying rate, indicated by fast absorption of paracetamol, the first study day and slow the second. It seemed that any intra or interindividual variation in gastric emptying rate arises from individual variations in antroduodenal motility. Diazepam tended to increase gastric emptying rate by enhancing the amplitudes of antral contractions and the motility index during phase II and pH of the gastric juice increased. Gastroduodenal motility was found to be normal in patients awaiting elective orthopedic or plastic surgery when premedicated with diazepam. pH of the gastric contents was not different from the findings in volunteers after administration of diazepam. All methods of general anaesthesia reduced the duration of the interdigestive motility complex, mainly by a reduction of phase II. General anaesthesia with halothane and enflurane depressed antral motility.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1914535 TI - Outcome from intensive care. A five year study of 1,308 patients. PMID- 1914536 TI - Central nervous system involvement in human immunodeficiency virus disease. A prospective study including neurological examination, computerized tomography, and magnetic resonance imaging. AB - Sixty-seven patients with different stages of human immunodeficiency virus (HIV) infection (47 CDC group IV, 20 CDC groups II or III) were followed prospectively for a median of 18 months with neurological examination, magnetic resonance imaging (MRI), and computerized tomography (CT) to evaluate the incidence of the AIDS dementia complex (CDC definition) and other neurological complications. Ten patients developed CNS opportunistic infection or malignancy. Among the remaining 57 patients, 12 of 37 (32%) belonging to CDC group IV, and 1 of 20 (5%) belonging to CDC groups II/III developed the AIDS dementia complex (p = 0.03). MRI white matter lesions occurred in 32% of CDC group IV patients and 5% of CDC groups II/III patients (p = 0.03). The corresponding figures for brain atrophy at CT were 71% and 30% (p less than 0.01) and for neurologic signs 49% and 20% (p = 0.06). The development of the AIDS dementia complex was significantly associated with the occurrence of MRI white matter lesions and a CD4 cell count of less than 200 x 10(6)/l, whereas it was not statistical significantly associated with brain atrophy at baseline. It is concluded that the AIDS dementia complex is a common feature of late stage HIV infection. Brain atrophy occurs in a large percentage of HIV infected patients, but the clinical significance of this atrophy is not clear. PMID- 1914537 TI - Changes in prescription of antibiotics in general practice in relation to different strategies for drug information. AB - The worldwide use of antibiotics is increasing with increasing costs and resistant bacteria as a consequence. The Danish use of antibiotics is one of the lowest in DDD/1,000 inhabitants/year; however, the use of ampicillin and co trimoxazole has been found to be too high. An information campaign in the beginning of 1987, using written material, stressed the importance of reducing the ampicillin and co-trimoxazole and increasing the penicillin usage in Denmark. This campaign was followed up by 10 lectures given by the same person in two (I and II) of the five counties of Zealand, Denmark. In county I, the lectures were given in meetings arranged by the local department of clinical microbiology. In county II, the lectures were given at meetings sponsored by a pharmaceutical company. The prescribing habits were generally changed significantly. In county I, the changes were significantly higher compared with counties only receiving written material. In county II, the prescribing habits did not change further compared with the counties only receiving written material. It is concluded that face-to-face information can improve the efficacy of written information, but sponsorship by pharmaceutical companies may weaken this efficacy. PMID- 1914538 TI - A perinatal audit of neonatal deaths in three Danish counties. AB - A perinatal audit of 109 neonatal deaths was carried out in three Danish counties (A, B and C) in order to investigate whether differences in the structure of antenatal care, delivery, and neonatal service had any influence on neonatal outcome and whether departure from generally accepted standards of satisfactory perinatal and neonatal care might have contributed to neonatal deaths. In the county (C) characterised by having no intensive neonatal care unit, significantly fewer liveborn infants with a gestational age of less than 28 weeks were reported to the Birth Register. County C had also significantly more potentially avoidable deaths compared with the county (B) which had a neonatal intensive care unit with specially trained staff available around the clock. The neonatal department in county A did not have specially trained doctors available in the hospital around the clock, and some cases of suboptimal care were caused by inadequate staffing and inappropriate decisions made by inexperienced junior doctors. The results indicate that it should be possible to improve the quality by having obstetric departments with access to neonatal intensive care units staffed with qualified personnel around the clock and by intensifying the postgraduate training of professionals performing peri- and neonatal care. PMID- 1914539 TI - Hereditary haemochromatosis in Denmark 1950-1985. Clinical, biochemical and histological features in 179 patients and 13 preclinical cases. AB - During the period 1950-1985, a total of 179 cases of clinically overt hereditary haemochromatosis (HH) were registered in Denmark, 140 males and 39 females. Median age at diagnosis was 55 years (range 29-81). Diagnostic approaches, symptoms and physical signs at discovery are described. All patients had grade 3 4 liver haemosiderin iron, and cirrhosis was present in 84%. Serum (S-) transaminase was elevated in 92%, S-alkaline phosphatase in 47% and S-bilirubin in 23%, while plasma prothrombin time was below normal in 34%. Females had higher alkaline phosphatase than males (p less than 0.05). Bone marrow haemosiderin iron (n = 81) showed no relation to iron status indicators and was unsuitable as a diagnostic tool. Skin biopsy (n = 56) was positive for haemosiderin iron in 67% and for melanin in 57%, but was of limited value in the assessment of HH. Arthropathy was registered in 44%; arthralgias and clinical joint abnormalities occurred more frequently in females than in males (p less than 0.05). Latent diabetes mellitus was found in 34% and overt diabetes in 55%, being more frequent in males than in females (p less than 0.05). Other endocrine abnormalities were seen in 66%. Cardiac failure was observed in 9% and abnormal ECG in 35%. Males had higher haemoglobin (p less than 0.0001) and S-iron (p less than 0.01) than females, while S-transferrin, transferrin saturation, S-ferritin and mobilizable iron stores showed no significant sex differences. Median transferrin saturation was 87% (range 52-100); values greater than 62% were observed in 96% of the patients. Median S-ferritin was 3,400 micrograms/l (800-12,700) and median iron stores 14.8 g (4.5-36.4). PMID- 1914540 TI - Dietary management of swallowing disorders. AB - Two major concerns in the dietary management of the dysphagic patient are to maintain adequate nutrition and to ensure safety during oral feeding. Dysphagic patients require modifications of standard hospital diets. Kitchen or nursing staff must remove from standard diet trays solid foods and liquids that pose swallowing hazards. Training kitchen and nursing staff and removing food are time consuming. It is also hazardous if certain foods are served to dysphagic patients through error or lack of knowledge. In addition, there is risk of inadequate nutrition when food is removed from trays. This paper proposes a four-level diet plan for patients who have difficulty swallowing solids and liquids. These diets gradually advance for patients undergoing treatment to improve swallowing function. The proposed diets save time for kitchen and nursing staff, reduce the risk of aspiration among patients, and serve as models for families as they prepare for discharge and meal planning at home. Diet guidelines are based on recommendations of the American Dietetic Association. PMID- 1914541 TI - Temporal reconstruction of sonographic imaging of disturbed tongue movements. AB - Documentation of tongue movement during swallowing has been restricted to the recording of fluorographic or ultrasound images on cine- or videofilm. The new approach of temporal sonographic imaging with reconstruction of one single image for the total act of swallowing presents a direct approach to obtaining substantial information concerning tongue movements and motility. The applicability of this reconstructed image for the documentation, interpretation, and comparison of tongue movements is demonstrated using examples of normal and pathologic swallowing. PMID- 1914543 TI - Achalasia and diet: assessment of the effect of achalasia on the diet of patients and their spouses. AB - The effect of achalasia on the diet of patients and their spouses was investigated using a validated questionnaire. The discordance between the diet of the patients and their respective spouses was compared with matched controls. There is no statistically significant difference between the discordance of case couples and control couples. Patients with achalasia, and their spouses, eat a normal diet. PMID- 1914542 TI - Biofeedback in the treatment of a selected dysphagic patient. AB - Electromyography and biofeedback techniques are well established in the disciplines of physical medicine for the retraining of muscle groups to approximate functional performance. This report documents the application of biofeedback techniques to the treatment of swallowing dysfunction in a selected dysphagic patient. PMID- 1914544 TI - Dysphagia occurring after polio. AB - Although they are delayed, progressive symptoms occurring after polio have recently received considerable attention, dysphagia in patients who have had polio has not been well-studied. The findings of historical, neurologic, and cineradiographic examinations in 13 patients with dysphagia who had had polio are presented. Historical evidence indicates that progressive dysphagia is among the worsening problems encountered by some patients several decades after their acute polio illness. Thorough evaluation of dysphagia symptoms in patients who have had polio is indicated to determine optimal feeding management and to search for treatable contributing factors. PMID- 1914545 TI - Pictorial review: principles of double-contrast pharyngography. AB - This pictorial essay will explain how to obtain quality double- contrast radiographs during pharyngography, present principles of the interpretation of double-contrast images of the pharynx, and show examples of benign and malignant pharyngeal tumors. PMID- 1914546 TI - Pleural fluid analysis in malignant mesothelioma. Prognostic implications. AB - Pleural fluid characteristics of 26 patients diagnosed with malignant mesothelioma over an 18-year period were reviewed and compared with those of patients with effusions due to other malignancies. Survival from time of initial thoracentesis was directly correlated with pleural pH and decreased pleural fluid/serum glucose ratios but was not related to protein or LDH concentration. Decreased pleural fluid pH was statistically related to a decreased pleural fluid/serum glucose ratio. Patients with low pH (less than 7.30) pleural effusions had statistically decreased mean survival and decreased mean pleural fluid/serum glucose ratios compared with patients with normal pH (greater than or equal to 7.30). Patients with malignant mesothelioma pleural effusions had statistically decreased mean pleural fluid pH compared with patients with other malignant pleural effusions. Decreased levels of pleural fluid pH and pleural fluid/serum glucose ratios have negative prognostic significance and probably correlate with the degree of tumor bulk affecting the pleural surface. PMID- 1914547 TI - Legionella pneumophila. A cause of severe community-acquired pneumonia. AB - In a prospective study of community-acquired pneumonias, 30 patients were diagnosed with Legionnaires' disease in 15 months. Clinical, laboratory and radiologic features of these patients are reviewed and compared with those who have pneumococcal pneumonia. Alcoholism, history of smoking, previous antimicrobial therapy, gastrointestinal and neurologic manifestations, elevations of serum transaminases, alkaline phosphatase and creatinine levels were more frequent in pneumonia due to Legionella pneumophila than in pneumococcal pneumonia. The presence of respiratory failure and radiologic progression were common findings that suggested L pneumophila as the etiologic agent of a community-acquired pneumonia. Development of respiratory failure was associated with involvement of several lobes and isolation of L pneumophila in any specimen. In 21 of 30 patients with Legionnaires' disease, L pneumophila was isolated from respiratory specimens. Overall mortality was 10 percent, but it increased to 27 percent in patients not treated with erythromycin initially. PMID- 1914548 TI - Lack of a relationship between induced changes in oxygen consumption and changes in lactate levels. AB - To determine whether the levels of oxygen consumption (VO2) required to relieve an existing oxygen debt are variable, increases in VO2 produced by increases in oxygen delivery (DO2) were evaluated longitudinally in septic patients with lactic acidosis and related to changes in lactate levels. Interventions were performed in 17 patients and consisted of fluid administration (n = 11), packed red blood cell transfusion (n = 19), or dobutamine infusion (n = 14). Interventions associated with a decreased lactate level or an unchanged/increased lactate level demonstrated similar increases from baseline VO2 (49 +/- 9 and 47 +/- 6 ml/min.m2, respectively) and similar postintervention absolute VO2 values (187 +/- 13 and 189 +/- 10 ml/min.m2, respectively) (both p greater than 0.6). When all interventions were considered, correlations were not observed between changes in lactate levels and changes in VO2 (r = 0.21, p greater than 0.60) or between changes in lactate levels and the postintervention VO2 values (r = 0.08, p greater than 0.45). These observations demonstrate that optimal levels of VO2 are variable and suggest that therapeutic interventions should be tailored to a patient's individual tissue needs and guided by an assessment of an oxygen debt (eg, lactate levels) rather than absolute VO2 measurements. PMID- 1914549 TI - Measuring the quality of well-being in cystic fibrosis and lung transplantation. The importance of the area under the curve. AB - The quality of well-being scale (QWB) has been used to measure overall life quality in a number of different clinical conditions, including cystic fibrosis and chronic obstructive pulmonary disease. Evidence supports its validity and reliability in both cross-sectional and longitudinal studies. One of the strengths of the QWB is that it is not organ-specific, so that it can take into account the broad impact of a disease and/or intervention, including unanticipated effects. The well-year of life is a concept that includes both morbidity and mortality: if a disease reduces quality of life by one-half, over a period of two years, that person can be said to have lost one full well-year. As we examine the impact of diseases such as cystic fibrosis, and of interventions such as lung transplantation, it is important to consider changes in overall well being over time to help individual patients and families make difficult therapeutic choices and to help formulate health policy. PMID- 1914550 TI - Acceptance of CPAP therapy for sleep apnea. AB - Although NCPAP is the most efficient nonsurgical treatment for patients with OSA, many patients do not accept sleeping with a nose mask. To determine the factors influencing acceptance, treatment with NCPAP was offered to 95 patients with an AHI greater than 15. After the first night on NCPAP, 47 of 65 patients decided to have NCPAP as a home therapy. Excessive daytime sleepiness was more frequently reported by acceptors than refusers. The frequency of complaints about psychomental symptoms such as poor mental performance and bad memory, was not different between the two groups. There was a close correlation between the rate of acceptance and the AHI as well as the number of positive answers to questions about symptoms of daytime sleepiness in a questionnaire, which correlated with the number and length of apneas. Acceptance of NCPAP was found to be dependent on the subjective feeling of impairment by hypersomnolence due to OSA. PMID- 1914551 TI - Nasal CPAP in nonapneic nocturnal asthma. AB - Nasal CPAP has been shown to improve nocturnal asthma in those patients with associated sleep apnea. We studied seven nonapneic, nonsnoring asthmatics to determine the effect of CPAP in this patient population. On the CPAP night vs the baseline night, there was a significant worsening of sleep architecture. This included increased awake time and decreased REM sleep. For the group, the overnight decrement in FEV1 was not improved. Of interest, two patients did have a marked improvement in FEV1 associated with improved oxygen saturation on the CPAP night. These individuals were restudied only on supplemental oxygen. This intervention also improved the overnight FEV1 and allowed the patients to have better sleep compared to the CPAP night. We concluded that CPAP is associated with disrupted sleep architecture in nonapneic asthmatics and nocturnal oxygen desaturation may play a role in the development of nocturnal asthma. PMID- 1914552 TI - The value of submucous needle aspiration in the prediction of surgical resection line of bronchogenic carcinoma. AB - The fiberoptic bronchoscope was used to perform a series of SMNAs from the tumor site in the bronchial tree toward the carina to decide on an appropriate surgical line of resection in 20 patients. The line of resection was examined histologically for tumor invasion. Of the 20 patients who underwent surgery 16 had lobectomies and four had pneumonectomies. Eighteen patients had no evidence of tumor invasion at the surgical resection site. Of the remaining two, one had a cancer-positive SMNA proximal to the resection line and demonstrated tumor cells in the surgical resection line. The second demonstrated tumor cells in the right lower and upper lobes with sparing of the right bronchus intermedius. This patient underwent lobectomy with subsequent resection of the remaining right upper lobe. On the basis of this experience we conclude that SMNA is effective in predicting the optimal surgical line of resection in lung carcinoma. PMID- 1914553 TI - Comparison of inspiratory work of breathing in T-piece breathing, PSV, and pleural pressure support ventilation (PPSV). AB - We have compared the inspiratory work of breathing during T-piece breathing, pressure support ventilation (PSV), and pleural pressure support ventilation (PPSV) by using a lung model with variable compliance and resistance, under simulated spontaneous breathing. Our lung model consists of two spring-loaded bellows, representing the lung and diaphragm, placed in an airtight container. Inspiration begins with the withdrawal of air from the diaphragm bellows by a time-cycled jet-flow-creating Venturi mechanism. Expiration occurs by opening the diaphragm bellows to the atmosphere. Work of breathing (WOB) is calculated by plotting the pressure-volume curve, with pressure corresponding to intrabox pressure and volume corresponding to the tidal volume; PPSV is a new mode of mechanical ventilatory support accomplished by setting the ventilator (Servo 900C) into the PSV mode with a level of 0 cm H2O, using the pleural pressure as the input and target signal. The PPSV maximally reduces WOB under any circumstances. The PSV sufficiently reduced WOB only in the normal lung and the lung with low compliance; however, a pressure supporting time is diminished in the lung with low compliance. The serious limitations of PSV remain in its application to the lung with high resistance. It is concluded that PPSV is closer to the actual patient's signal and has a potential advantage in reducing WOB in the lung with low compliance or high resistance (or both). The lung with flow limitation is still a challenging issue for mechanical ventilatory assistance. PMID- 1914555 TI - Postcoital asthma and rhinitis. AB - Sexual intercourse as a trigger factor for attacks of asthma and/or rhinitis and the morbidity caused thereof is not well recognized. We present four patients (three males and one female) with postcoital asthma and/or rhinitis. Acute severe asthma subsequent to sexual intercourse in one male patient had resulted in several emergency department visits and hospitalization on one occasion. Anxiety was a predominant feature in the patients and their spouses that had interfered with their sexual life and worsened their disease. Late asthmatic response, on occasions, occurred in two patients. None of the patients developed wheezing dyspnea or rhinitis, nor did they have a fall in peak expiratory flow rates on climbing two flights of stairs, an exercise considered equivalent to energy expended during sexual intercourse. Thus, sexual excitement rather than exercise appeared to be the cause of postcoital asthma and rhinitis. Adequate pharmacotherapy along with counseling of the patients and their spouses restored normal sexual function and control of asthma and rhinitis. Postcoital asthma and rhinitis can easily be overlooked due to patient embarrassment and lack of physician awareness. PMID- 1914554 TI - Transdermal delivery of the alpha 2-agonist clonidine does not alter airways responses to inhaled histamine or methacholine. AB - Previous studies have reported that the inhalation of the alpha 2-agonist clonidine decreases airways reactivity. Other studies have shown that oral doses of clonidine acutely increase airways reactivity to histamine, but not to methacholine. Recently, a transdermal clonidine delivery system (TTS) has been approved for use, and there is an increasing interest in using this system for management of postmenopausal and smoking cessation symptoms. To our knowledge, the effects of TTS on airways function in asthmatics have not been reported. The purpose of this study was to determine if use of TTS would alter airways reactivity. Six asymptomatic asthmatic subjects underwent a baseline methacholine challenge (M). In a double-blinded randomized crossover fashion, either a placebo or a TTS patch (TTS-1, 0.1 mg/day), was applied to the arm. Four days later, the challenge was repeated. After two to three days of washout, the alternate patch was applied, and a second challenge was performed. Several days later, a second baseline challenge was repeated. This sequence was then repeated using histamine (H). The patch was well tolerated by all subjects. There was no significant change in resting pulse or blood pressure, and for the group no change in airways reactivity to either M or H was noted. In conclusion, while use of TTS-1 does not improve airways function, its short-term use in asthmatics is not associated with an increase in airways reactivity. PMID- 1914556 TI - Cooperation between accessory cells and T lymphocytes in patients with tuberculous pleurisy. AB - We studied interleukin 1 (IL-1) activity of pleural fluid macrophages and peripheral blood monocytes obtained from ten patients with tuberculous pleurisy and ten patients with malignant pleurisy, using purified protein derivative (PPD) as a stimulating agent. Tuberculous pleural fluid macrophages and peripheral blood monocytes tended to produce higher IL-1 activity than malignant pleural fluid macrophages and blood monocytes and showed significantly more IL-1 activity than healthy control monocytes. However, no significant difference in IL-1 activity was observed between tuberculous pleural macrophages and blood monocytes. With the cooperation of these accessory cells, pleural fluid T lymphocytes in patients with tuberculous pleurisy showed a significant level of interleukin 2 (IL-2) activity in the presence of PPD. Tuberculous pleural fluid macrophages promoted greater IL-2 production than blood monocytes from either tuberculous pleural fluid or blood T lymphocytes despite relative equivalence in measured IL-1 production. Combination of tuberculous pleural fluid macrophages and pleural fluid T lymphocytes was the most effective for increasing IL-2 activity when compared with other combinations. These results suggest that tuberculous pleural fluid macrophages and T lymphocytes may contribute to the immunopathogenesis of tuberculosis at a local site of disease. PMID- 1914558 TI - Usefulness of carcinoembryonic antigen determination in bronchoalveolar lavage fluid. A comparative study among patients with peripheral lung cancer, pneumonia, and healthy individuals. AB - We compared carcinoembryonic antigen (CEA) levels in bronchoalveolar lavage (BAL) fluid and serum of patients with lung cancer, pneumonia, and healthy individuals to determine the usefulness of CEA in diagnosing lung cancer not visible endoscopically. Cancer patients had CEA lavage fluid levels (4,650 +/- 1,565 ng/mg of albumin) significantly higher than pneumonia patients (755 +/- 346 ng/mg) or healthy individuals, smokers (252 +/- 48 ng/ml), and non-smokers (175 +/- 6 ng/mg). In serum, CEA assay cannot discern between cancer (35 +/- 13 ng/ml) and pneumonia (4.6 +/- 1.4 ng/ml) (p = 0.06). Using 1,000 ng/mg of albumin as the cutting point in BAL fluid, sensitivity and specificity were 77 percent and 94 percent, respectively. In serum, 5 ng/ml provided a sensitivity of 55 percent and specificity of 91 percent. Positive and negative predictive values were 77 percent and 94 percent in BAL, respectively, and 62 percent and 89 percent in serum, respectively. Using a combination of serum and BAL fluid CEA levels, the sensitivity and specificity were 88 percent and positive and negative predictive values were 66 percent and 96 percent, respectively. When used in combination with serum levels of CEA or transbronchial biopsy, the diagnostic yield increased up to 88 percent. Thus, although CEA determination in BAL fluid improves diagnostic yield, it should not be used as the only diagnostic procedure. PMID- 1914557 TI - Cardiac dysfunction and pulmonary edema following scorpion envenomation. AB - Cardiac dysfunction with pulmonary edema following scorpion envenomation (SE) has been documented only in a few isolated case reports. We conducted a systematic hemodynamic study in five consecutive patients (mean age, 21.6 +/- 8 years) presenting with pulmonary edema occurring a few hours (9.6 +/- 5.2 hours) after SE. All patients had increased pulmonary capillary wedge pressure (mean, 25 +/- 1.8 mm Hg) while the systemic vascular resistance was elevated only in one. The stroke volume index was markedly depressed (21.7 +/- 3.6 ml/sq m) whereas cardiac index was normal or slightly decreased (2.5 +/- 0.4 L/min/sq m). Cerebral infarct and sudden cardiac arrest were the cause of death in two patients. In the three survivors, all the hemodynamic disturbances and respiratory abnormalities disappeared within a few days. We conclude that cardiac dysfunction was found in all five patients and this was reversible in the three surviving the acute episode. PMID- 1914559 TI - Conversion of COPD patients from multiple to single dose theophylline. Serum levels and symptom comparison. AB - The objective of the present study was to determine if patients with COPD who were taking Theo-Dur bid or tid (total dose 400 to 900 mg per day) could be safely switched to Uni-Dur, 800 mg given qd at bedtime. Twenty-eight patients were enrolled in the study, and 23 completed the study. The mean daily dose of theophylline prior to the study was 828 mg, while the mean dose after three weeks of Uni-Dur therapy was 783 mg. The mean serum theophylline level 10.5 +/- 3.6h after the last Theo-Dur dose was 10.5 mg/L. After three weeks of Uni-Dur therapy, the mean theophylline level at 8:00 AM was 14.6 mg/L, while the mean theophylline level at 8:00 PM was 9.9 mg/L. This latter level did not differ significantly from that obtained at the start of the study 10.5 +/- 3.6 h after the last dose of Theo-Dur. After three weeks of Uni-Dur therapy, the peak expiratory flow rate, the FEV1, and the FVC were not significantly changed from those at the initial evaluation. Twenty-one of the 23 patients ended up receiving 800 mg Uni-Dur qd. From this study, we conclude that once daily theophylline dosing with Uni-Dur compared with bid or tid dosing with Theo-Dur produces similar theophylline levels and pulmonary function, and most COPD patients who are taking 400 to 900 mg Theo-Dur daily can be managed with 800 mg Uni-Dur once daily at bedtime. PMID- 1914560 TI - Fluid balance during pulmonary edema. Is fluid gain a marker or a cause of poor outcome? AB - STUDY OBJECTIVE: To evaluate the importance of fluid balance and changes in extravascular lung water (EVLW) on survival in the ICU and short-term outcome in patients with pulmonary edema. DESIGN: Retrospective analysis of data (sorting by survival and "treatment received") from a recent randomized controlled trial of fluid restriction in this population. SETTING: Medical ICU of a university affiliated, tertiary-care medical center. PATIENTS: Eighty-nine patients (from the previously mentioned study) requiring pulmonary artery catheterization with abnormally high EVLW (greater than 7 ml/kg). MEASUREMENTS AND RESULTS: When analyzed by survival, the survivors had no significant fluid gain or change in EVLW but decreased wedge pressure and body weight, compared to nonsurvivors. When analyzed by fluid balance, patients who gained less than 1 L of fluid by 36 hours into the study had a better rate of survival (74 percent) than the rest (50 percent; p less than 0.05). Also, the median duration of days on the ventilator, ICU days, and days of hospitalization was approximately half as long for each variable in the group with less than 1 L of fluid gain. Even accounting for baseline differences in the severity of illness, fluid balance was an independent predictor of survival (p less than 0.05). When analyzed by whether or not EVLW decreased by more than 15 percent between the first and last measurement, only patients with ARDS or sepsis had decreased days on the ventilator and ICU days. CONCLUSIONS: These data support the concept that positive fluid balance per se is at least partially responsible for poor outcome in patients with pulmonary edema and defend the strategy of attempting to achieve a negative fluid balance if tolerated hemodynamically. PMID- 1914561 TI - High-volume, low-pressure cuffs. Are they always low pressure? AB - Ischemic tracheal complications due to the ETT cuff occur in approximately 10 percent of mechanically ventilated critically ill patients despite the use of high-volume, low-pressure ETT cuffs. Using a laboratory model, we studied the effects of airway pressure on three different ETT cuff designs, including two "low pressure" designs. Positive airway pressure acted on the "low pressure" cuffs to create a "self-sealing" effect that maintained tracheal occlusion despite airway pressures that exceeded cuff inflation pressure. Increases in airway pressure caused by decreased lung compliance resulted in higher cuff inflation pressures in all three groups, with the smallest increase occurring in the design that had the longest tracheal contact length. We conclude that the current high-volume, low-pressure ETT cuff design currently used does not guarantee low cuff pressure when high airway pressures occur, and an alternative design should be developed. PMID- 1914562 TI - Pressure support. Changes in ventilatory pattern and components of the work of breathing. AB - To evaluate the interaction between patient and ventilator during widely varying levels of pressure support (PS) ventilation, we studied 33 patients who had undergone aortocoronary bypass. All patients were without preoperative evidence of lung disease and had left ventricular ejection fractions greater than 45 percent. We assessed both changes in ventilatory pattern and the use of an extension of the Campbell technique to determine the components of the mechanical work of breathing (WOB). Patients were placed on 0, 10, 20, and 30 cm H2O of PS. We found that increasing the pressure support level (PSL) did not change minute ventilation, PCO2, or pH despite large changes in both rate and depth of breathing. The inspiratory time fraction was consistently and progressively reduced as PS increased. Although mean inspiratory flow (MIF) increased by 75 +/- 9 (SE) percent as the PSL increased to 30 cm H2O, mean airway pressure rose only 3.5 +/- 0.1 cm H2O. Observed changes in the resistive and elastic components of WOB at PSL greater than 0 were consistent with values predicted from baseline observations and changes in VT and MIF demonstrating that the Campbell technique of separating resistive and elastic components of the patient's WOB during unassisted ventilation can be extended to the analysis of WOB during mechanical ventilation. We were surprised to observe that although inspiratory WOB fell 67 +/- 13 percent as the PSL increased to 30 cm H2O, postinspiratory work by the inspiratory muscles (WOBPIIM) did not show significant change. The persistence and substantial values of WOBPIIM in some patients suggested the presence of significant patient-ventilator dyssynchrony, especially at higher levels of PS. Total inspiratory WOB per minute, including both patient WOB and WOB by the ventilator, increased by 186 +/- 29 percent, demonstrating that PS results in a respiratory pattern requiring substantially greater total mechanical work. PMID- 1914563 TI - Guidewire catheter change in central venous catheter biofilm formation in a burn population. AB - This study was designed to assess the risk of colonization and biofilm formation of central venous catheters left in situ for seven days vs those changed over a guidewire at three days and removed at seven days. Colonization was determined using scanning and transmission electron microscopy and compared to a special scraping/sonication culture method. Thirty-one catheters were examined, and no difference was found between catheters left in situ (9 of 16 colonized) and those changed over a guidewire (11 of 15 colonized). Colonization rates rose significantly from 4 of 15 catheters at the time of guidewire change to 11 of 15 at 7 days (p less than 0.001). Of the catheters defined as colonized by SEM, the special culture technique showed bacterial growth in only 35 percent, making a negative culture result of dubious value in ruling out catheter colonization. No beneficial effect of guidewire changes in reducing colonization could be demonstrated. PMID- 1914564 TI - A computer-controlled ventilator weaning system. AB - Weaning of patients from mechanical ventilation is a time-consuming, labor intensive process. Because most weaning decisions are based on objective data, we tested a computer-directed weaning system on postoperative patients. We developed an automatic, computer-controlled ventilator weaning system which interfaces a laptop computer to a ventilator and a pulse oximeter. The laptop computer program accesses patient data through the ventilator and pulse oximeter to make weaning decisions. The computer directly controls the ventilator through an interface developed for this system. We tested the system in nine postoperative patients who met the following criteria: negative inspiratory force less than or equal to 20 cm H2O, vital capacity greater than 10 ml/kg, inspired oxygen concentration less than or equal to 40 percent, and satisfactory arterial blood gas parameters (pH between 7.32 and 7.48, PCO2 between 32 and 48, and oxygen saturation greater than or equal to 90 percent). The computer decreased the SIMV rate by 2 breaths/min every 5 min until a rate of 2 breaths/min was reached, then decreased pressure support by 4 cm H2O every 5 min as long as the patient met the following criteria: respiratory rate between 8 and 25 breaths/min, minute ventilation between 6 and 14 L, and pulse oximeter oxygen saturation greater than or equal to 90 percent. If unsatisfactory weaning criteria were noted, the system automatically returned the patient to the previous weaning level. We successfully weaned nine patients using the system. Additional studies are underway to determine if this system can be used in medical patients. We believe this computer-controlled ventilator weaning system can be used successfully in patients requiring mechanical ventilation and may decrease the time and cost associated with the care of these patients. PMID- 1914565 TI - The environmental impact of chlorofluorocarbon use in metered dose inhalers. PMID- 1914566 TI - Aerosol bronchodilator delivery during mechanical ventilation. Nebulizer or inhaler? PMID- 1914567 TI - Care-giver protection from exposure to aerosolized pharmacologic agents. Is it necessary? PMID- 1914568 TI - Aerosol consensus statement. Consensus Conference on Aerosol Delivery. PMID- 1914569 TI - Anti-inflammatory therapy for acute lung injury. A review of animal and clinical studies. AB - The adult respiratory distress syndrome (ARDS) continues to demonstrate high mortality. This syndrome is frequently observed as a remote complication of another disease process and is characterized by a significant inflammatory component. The purpose of this review is to compare and contrast published research on the use of anti-inflammatory agents, steroidal and nonsteroidal, in animal models of acute lung injury. Emphasis is given to the nature of the experimental pulmonary injury, infusion (ie, oleic acid and zymosan-activated plasma) or bacteriologically (ie, endotoxin and live bacteria) induced and the timing of drug administration relative to induction of the insult. The clinical data available on the use of these drugs in ARDS are discussed, and a rationale is presented for future clinical trials in these patients. PMID- 1914570 TI - Drug-induced noncardiogenic pulmonary edema. PMID- 1914571 TI - Transesophageal and Doppler echocardiography in the diagnosis and management of infective endocarditis. PMID- 1914572 TI - Suddenly swollen neck associated with respiratory failure. PMID- 1914573 TI - The effect of tumor necrosis factor on vascular smooth muscle. In vitro studies using rat aortic rings. AB - The mechanisms of vasodilation in septic shock have not been well elucidated. We used isolated rat aortic rings as an in vitro model of vascular reactivity to assess the acute, direct effects on vascular smooth muscle relaxation of four cytokines: interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6), and tumor necrosis factor (TNF). The rings were precontracted with catecholamines and then test cytokines were added. The changes in tension with IL-1 at 1,000 U/ml, IL-2 at 1,000 U/ml, and IL-6 at 500 U/ml differed from controls by -67 +/- 59, -5 +/- 42, and 8 +/- 56 mg/mg of tissue, respectively (for each, n = 10, p = NS). The change in tension with TNF at 1,000 U/ml differed from controls by -176 +/- 42 mg/mg of tissue (n = 20), p less than 0.001). Chemical removal of the endothelium with deoxycholate diminished TNF-induced vasodilation to -62 +/- 14 mg/mg of tissue (p less than 0.05). The relaxation with TNF occurred in a concentration-dependent fashion and was unaffected by indomethacin. This study demonstrates that TNF has an acute, concentration-dependent, cyclooxygenase independent, vasodilatory effect on vascular smooth muscle. The effect of TNF was partially, but not fully, dependent on the presence of an intact endothelium, implying that TNF acts on both the endothelium and the smooth muscle. These findings suggest that TNF may play an important role in the vasodilation characteristic of septic shock. PMID- 1914574 TI - Pulmonary "capillary" wedge pressure not the pressure in the pulmonary capillaries. AB - In 1949, Hellems, Haynes, and Dexter proposed that the pressure in a catheter wedged so as to occlude a pulmonary artery was an "estimate" of the pressure in the pulmonary capillaries. Their report led to the designation of this pulmonary artery wedge pressure as the pulmonary "capillary" wedge pressure. In fact, the pulmonary artery wedge pressure is a distorted measure of the pressure in the pulmonary veins. Usually this pressure differs only slightly from the capillary pressure, and the misconception fostered by the inaccurate name is inconsequential; however, sometimes this misconception leads to errors in diagnosis. This report briefly reviews the early history of pulmonary vascular catheterization, offers an explanation of pulmonary artery wedge pressure, and discusses a disease in which pulmonary artery wedge pressure is normal, even though capillary pressure is elevated. PMID- 1914575 TI - Bronchoscopically induced bleeding. A summary of nine years' Cleveland clinic experience and review of the literature. PMID- 1914576 TI - Needle brush in the diagnosis of lung mass or nodule through flexible bronchoscopy. AB - Transbronchial needle aspiration (TBNA), in comparison with cytology brush and forceps biopsy, in the diagnosis of a pulmonary mass or coin lesions has been studied by Shure and Wang in the past. Both studies concluded that TBNA markedly increased the diagnostic yield. A new instrument, a "needle brush" (Mill Rose Lab), has been developed and compared with the following three instruments: a regular cytology brush was used first, followed by needle brush, TBNA, and forceps biopsy under fluoroscopy. Twenty-four patients were studied. A specific diagnosis was made in 16 patients (15 malignancies; one granuloma); in three patients, results were suspicious for malignancy, three patients had negative results, and in two patients the study was not complete. "Needle brush" biopsy was positive in 11 patients (exclusively in four); TBNA was positive in eight (exclusively in two). Regular brush biopsy was positive in seven (exclusively in none). Forceps biopsy was positive in four (exclusively in one; granuloma). We conclude that the needle brush and TBNA have a higher diagnostic yield in malignant lung masses or nodules. The use of regular brush and forceps biopsy did not increase the diagnostic yield in malignancy. Forceps biopsy might be more useful in benign diseases. PMID- 1914577 TI - Physiologic evaluation of bullous emphysema. PMID- 1914578 TI - Interstitial pneumonitis associated with "crack" cocaine abuse. AB - A 33-year-old woman developed acute bilateral pulmonary infiltrates after the intense use of rock cocaine (crack). She subsequently had progressive deterioration of pulmonary function to the point of being ventilator-dependent. Open lung biopsy showed a chronic interstitial pneumonia with extensive accumulation of free silica within histiocytes associated with mild pulmonary fibrosis. This pattern of interstitial pneumonia has not been previously reported in crack users. PMID- 1914579 TI - Patent foramen ovale associated with platypnea and orthodeoxia. AB - A case of positionally symptomatic right-to-left shunting across a patent foramen ovale with both platypnea and orthodeoxia despite normal pulmonary arterial pressures and normal right ventricular function is documented. When the patient was in a supine position, the calculated right-to-left shunt was 12.8 percent, and when seated 25 percent. Surgical closure of the patent foramen ovale relieved the symptoms and positionally induced shunting. The prevalence and associations of permanent and intermittent patency of the foramen ovale are discussed. It is recommended that those at risk of thromboembolism be screened for patency by contrast ultrasound or color flow techniques. If present, surgical closure needs to be considered to prevent paradoximal embolism and stroke. PMID- 1914581 TI - Localization of occult bronchogenic carcinoma by bronchography. AB - Bronchography is seldom recommended today to localize radiographically and bronchoscopically occult bronchogenic carcinoma. We report a case in which bronchography promptly localized such a tumor that had been occult to multiple bronchoscopies and chest computed tomograms (CTs). The patient is free of recurrence 32 months after lobectomy. Bronchography should be considered when bronchoscopies and CT fail to reveal a radiographically occult carcinoma. PMID- 1914580 TI - An unusual cause of respiratory alkalosis. AB - A 56-year-old man with a longstanding tracheostomy presented to the hospital with upper GI bleeding and was found to have a profound respiratory alkalosis. The cause of this patient's involuntary hyperventilation was hiccuping complicated by the absence of glottic closure. PMID- 1914582 TI - Essential thrombocythemia associated with angina pectoris with unusual coronary artery findings. AB - A case of ET associated with angina pectoris is presented. Angiography showed a 3.0-cm long mosaic-like thrombus shadow consisting of small filling defects in the proximal left anterior descending artery. The lesion could not be reduced with warfarin, ticlopidine, trapidil, urokinase or melphalan. Coronary artery bypass grafting was performed successfully. PMID- 1914583 TI - Failure of radiotherapy to resolve fatal lung damage due to paraquat poisoning. AB - The most effective treatment of severe paraquat poisoning in man is uncertain. In order to prevent pulmonary fibrosis, we employed radiotherapy of both lungs in a 23-year-old patient with severe paraquat poisoning; however, it failed to prevent the fatal outcome. PMID- 1914584 TI - Recurrent massive pleural effusion as a late complication of radiotherapy in Hodgkin's disease. AB - We report a very unusual case of a patient with recurrent massive PEs eight years after mediastinal radiotherapy for HD, in which evidence of lymphomatous recurrence could not be demonstrated. The diagnosis of PE as a complication of radiation is presumptive, and other disorders causing PE must be excluded. This condition requires symptomatic treatment and a close follow-up of the patient. PMID- 1914585 TI - Anomalous origin of the left main coronary artery from the right aortic sinus of Valsalva with vasospastic angina. AB - A case of anomalous origin of the left main trunk of the coronary artery from the right aortic sinus of Valsalva with vasospastic angina is described. Vasospasm was induced in the left main coronary artery by intracoronary administration of ergonovine. To our knowledge, this is the first reported case of vasospastic angina occurring in the presence of the anomalous origin of the left main coronary artery from the right aortic sinus. PMID- 1914586 TI - Cardiorespiratory arrest following peak expiratory flow measurement during attack of asthma. AB - We report two episodes of cardiorespiratory arrest immediately after measurement of peak expiratory flow in two young asthmatic subjects during an attack of asthma. Various mechanisms could be involved, particularly airway inflammation. PMID- 1914587 TI - Plasma cell pneumonia induced by Legionella pneumophila. AB - We report a case of severe Legionella pneumonia in which the histopathologic features of an open lung biopsy specimen were characterized by a monotypic plasma cell infiltrate and absence of granulocytes or other acute inflammatory cells. The clinical course was otherwise typical for a severe case of Legionella pneumonia with complete functional and roentgenographic recovery following a prolonged convalescence. We speculate on possible reasons for this patient's unusual histopathologic features. PMID- 1914588 TI - Ventilator autocycling due to an endotracheal tube cuff leak. AB - Ventilator autocycling can occur with any ventilator if the sensitivity is improperly set or if a gas leak exists in the respiratory system which creates a negative change in proximal airway pressure. We report a case of ventilator autocycling in a paralyzed patient secondary to an endotracheal cuff leak which was misconstrued as assisted ventilation. We believe this is the first report of autocycling due to a cuff leak. PMID- 1914589 TI - Subacute left ventricular free wall rupture. Surgical repair prompted by echocardiographic diagnosis. AB - Subacute cardiac rupture may occur in patients with electrocardiographic and enzyme evidence of transmural myocardial infarction. In the unusual case we encountered, these changes were absent. The echocardiographic observation of an echo-dense area within the pericardial space, due to an organized thrombus, provided early diagnosis of cardiac rupture and prompted surgery. PMID- 1914590 TI - Acute pulmonary effects of aerosolized pentamidine. PMID- 1914591 TI - Subpleural mononuclear cell infiltration in nonspecific pleuritis. PMID- 1914593 TI - Percutaneous tracheostomy. PMID- 1914592 TI - Gravity-dependent lung infiltrates. PMID- 1914594 TI - Fiberoptic bronchoscopy without premedication. PMID- 1914595 TI - Coronary arterial spasm and cardiac arrest following mediastinal radiation therapy for Hodgkin's disease. PMID- 1914596 TI - Serum lactate dehydrogenase in interstitial lung disease. PMID- 1914597 TI - Pleural fluid acidosis associated with pancreatic pseudocyst. PMID- 1914598 TI - Pneumothorax during pulmonary toxoplasmosis in an AIDS patient. PMID- 1914599 TI - The malignancy-sarcoidosis syndrome. PMID- 1914600 TI - ARDS: inflammation, infections, and corticosteroids. PMID- 1914601 TI - Beneficial effects of reducing pulmonary edema in patients with acute hypoxemic respiratory failure. PMID- 1914602 TI - Management of parapneumonic effusions. PMID- 1914603 TI - Leftward shift of the interventricular septum and pulsus paradoxus in obstructive sleep apnea syndrome. AB - Echocardiograms were taken from the parasternal long axis view during nocturnal sleep in ten patients diagnosed with OSAS. A table designed to support the echocardiographic probe prevented significant sleep disturbances during monitoring and allowed continuous data collection with and without nasal CPAP administration. In five of ten patients, there was before CPAP treatment a diastolic LSIVS during NREM sleep, inducing a flattening of the left ventricle. Arterial blood pressure recordings showed pulsus paradoxus when LSIVS was occurring. Nasal CPAP led to normal, unobstructed breathing, significant decrease in Pes nadir and disappearance of LSIVS and pulsus paradoxus. Increase in left ventricular afterload and increase in total peripheral resistance could lead to hypertrophy and hypertension in some OSAS patients. The presence of pulsus paradoxus in OSAS indicates a marked increase in Pes nadir, and its disappearance with nasal CPAP may be one of the signs of effective treatment of OSAS. PMID- 1914604 TI - Increased lung permeability following long-term use of free-base cocaine (crack). AB - The clearance of inhaled 99mTc DTPA aerosol from the lungs is used as an index of lung epithelial permeability. Using the radioaerosol method, we investigated the effects of long-term "crack" (free-base cocaine) inhalation on lung permeability in 23 subjects. Eighteen control subjects (12 nonsmokers and 6 cigarette smokers) with no history of drug use were also studied. Subjects inhaled approximately 150 muCi (approximately 5.6 MBq) of 99mTc DTPA aerosol and quantitative gamma camera images of the lungs were acquired at 1-min increments for 25 minutes. Regions of interest (ROIs) were selected to include the following: (1) both lungs; (2) each individual lung; and (3) the upper, middle, and lower thirds of each lung. 99mTc DTPA lung clearance was determined from the slopes of the respective time activity plots for the different RIOs. Radioaerosol clearance half-times (T1/2) for the seven nonsmoking crack users (61.5 +/- 18.3 minutes) were longer than for the seven cigarette-smoking crack users (27.9 +/- 16.9 minutes) and nine cigarette-smoking crack plus marijuana users (33.5 +/- 21.6 minutes). T1/2 for the nonsmoking crack users was significantly shorter (p less than 0.001) than for the nonsmoking control group (123.8 +/- 28.7 minutes). T1/2 for the cigarette smoking drug users was similar to that of the cigarette-smoking control group (33.1 +/- 17.8 minutes), suggesting a similar mechanism of damage from the smoke of crack and tobacco. From these groups, one nonsmoker and 11 cigarette smokers displayed biexponential 99mTc DTPA clearances, indicative of greater lung injury than found in the usual cases of monoexponential clearance. The upper lungs of all crack users groups cleared faster than the lower lungs. The faster and biexponential clearance properties of inhaled 99mTc DTPA aerosol were the principal functional abnormalities found in all the drug users. In contrast, 19 of 23 crack users had normal spirometry and gas exchange. These results indicate that 99mTc DTPA may provide a sensitive and useful assay to evaluate the physiologic effects of cocaine inhalation in the lung. PMID- 1914605 TI - Left ventricular ejection fraction in obstructive sleep apnea. Effects of long term treatment with nasal continuous positive airway pressure. AB - The effects of treatment with nasal continuous positive airway pressure (CPAP) on left ventricular ejection fraction (LVEF) were assessed in 29 patients with obstructive sleep apnea (OSA) in a prospective study using multiple gated equilibrium radionuclide angiocardiography. All patients were evaluated before CPAP treatment was initiated and were reevaluated after one year (mean +/- SE, 415 +/- 6 days), of home treatment with nasal CPAP. The mean LVEF increased from 59 +/- 1 percent to 63 +/- 1 percent (p less than 0.005). The degree of improvement in LVEF was correlated with baseline LVEF (r = 0.54; p less than 0.003), meaning that the lower the baseline value, the greater the increase with treatment. The changes were not different when subgroups of medicated and unmedicated patients were considered separately. These results show that long term nasal CPAP treatment results in improved left ventricular function in OSA. PMID- 1914606 TI - Childhood asthma and the indoor environment. AB - To investigate the influence of indoor air quality on respiratory health, a questionnaire-based study of 17,962 Canadian schoolchildren in kindergarten through grade 2 was carried out in 1988. The present report focuses on associations between several indoor environmental factors and childhood asthma. Increased reports of physician-diagnosed asthma were significantly associated (p less than 0.001) with exposure to environmental tobacco smoke (OR = 1.4), living in a damp home (OR = 1.5), the use of gas for cooking (OR = 2.0) and the use of a humidifier (OR = 1.7). Wheezing without a diagnosis of asthma also was associated (p less than 0.01) with environmental tobacco smoke (OR = 1.4, home dampness (OR = 1.6) and humidifier use (OR = 1.4), but not with gas cooking. Thus, several modifiable risk factors for respiratory illness may exist in Canadian homes. Further research is required to determine the nature of these cross-sectional observations. PMID- 1914607 TI - Indices of nonspecific bronchial responsiveness in a pediatric population. AB - A cross-sectional survey of the prevalence of asthma and bronchial hyperreactivity among schoolchildren (7 to 11 years old) was carried out in three areas of the Latium region (Central Italy). Out of 1,777 children tested with methacholine challenge (MCT), 15.1 percent had a 20 percent fall in FEV1 after a provocative concentration (PC20FEV1) of 4 mg/ml of methacholine or less; 69.7 percent had a PC20FEV1 less than 64.0 mg/ml, whereas 50.3 percent were nonresponders. Two continuous measures of bronchial responsiveness, the slope (percentage of change in FEV1 per mg/ml of methacholine) and the area under the dose response curve, were calculated in order to avoid the loss of information in nonresponders. Applying a receiver operating characteristic (ROC) curve analysis, the three estimators did not show any statistically significant difference in their overall performance in detecting asthma (ROC areas: PC20FEV1 = 0.683, slope = 0.681, area = 0.702 or asthma-like symptoms. The log transformation of slope, having a unimodal and slightly skewed shape, is an appealing continuous measure of bronchial responsiveness useful for epidemiologic studies. The final choice of an appropriate estimator of the concentration-response curve to methacholine, however, depends upon both the statistical tests or the modelling procedures to be used and clarification of the prognostic value of different indices of bronchial responsiveness. PMID- 1914608 TI - Characteristics of asthma among elderly adults in a sample of the general population. AB - This article describes the characteristics and course of asthma among subjects who were older than 65 years at the time of enrollment in a longitudinal study of a general population sample. It was present in 3.8 percent of men and 7.1 percent of women. An additional 4.1 percent of men reported having "asthma," but they also had seen a physician for "emphysema" and had smoked significantly; their "asthma" diagnosis is regarded as highly questionable. They did not show the elevated rate of allergy skin test reactivity of high serum IgE levels that were characteristic of other asthmatics. Many of the elderly asthmatics (mean age, 72 years) had severe disease with marked ventilatory impairment. There was a close relationship between the severity of wheezing complaints and impairment of the FEV1. Of the 46 patients, 48 percent reported an onset before age 40 years. There was no relationship between severity and age of onset or duration of disease. A second diagnosis of "chronic bronchitis" was reported by 46 percent of the asthmatics, but this did not delineate a distinctive group with late-onset, smoking-related disease. Death rates in the asthmatics tended to be higher than in nonasthmatics (odds ratio, 1.9; CI, 0.998 to 3.70, after stratifying by sex). Over a mean follow-up of 7.44 years, most symptoms as well as the FEV1 remained relatively stable. Chronic productive cough did tend to remit (p less than 0.01), but this was noted in the nonasthmatics as well. We estimate that no more than 19 percent of the asthmatics went into complete remission during follow-up. Most of these had mild initial symptoms; there were no remissions in subjects with severe disease at the time of entry. We concluded that asthma in the elderly is not a rare disease and may be associated with severe symptoms and chronic airways obstruction. If severe, it rarely goes into complete remission but tends to remain a severe, disabling disorder. PMID- 1914609 TI - Fibroproliferative phase of ARDS. Clinical findings and effects of corticosteroids. AB - Most patients with adult respiratory distress syndrome (ARDS) survive the initial insult which caused respiratory failure only to succumb later to sepsis caused by nosocomial pneumonia or to pulmonary fibrosis. Clinical criteria and analysis of the tracheal aspirate are notoriously inadequate for establishing a diagnosis of ventilator-associated pneumonia. We implemented a comprehensive diagnostic protocol to determine the cause of sepsis in ARDS patients who had been ventilated for more than three days and who had no bronchoscopic evidence of pneumonia. Nine patients with late ARDS who had fever (89 percent), leukocytosis (89 percent), a new localized infiltrate (78 percent), purulent tracheal secretions (89 percent), low systemic vascular resistance (50 percent), and marked uptake of gallium in the lungs (100 percent) had no source of infection identified. Open-lung biopsy specimens from seven patients showed the fibroproliferative phase of diffuse alveolar damage and confirmed absence of pneumonia. Treatment with prolonged high doses of corticosteroids was associated with a marked and rapid improvement in lung injury score (p less than 0.003 at five days). Our findings indicate that the fibroproliferative process occurring in the lungs of patients with late ARDS gives rise to clinical manifestations identical to those of pneumonia and is potentially responsive to steroid treatment. PMID- 1914610 TI - Comparative studies using a rigid thoracoscope and fiberoptic bronchoscope to treat spontaneous pneumothorax. AB - Prior to 1978, the conventional treatment of pneumothorax generally consisted of conservative therapies such as rest, needle puncture, or thoracic cavity drainage; however, when conservative therapies were ineffective or relapse occurred therapeutic approach, 34 percent (11/32) of our patients required a thoracotomy. Consequently, in 1981, we began to use alternative therapies to reduce the need for thoracotomy. In this report, we describe the results of using a rigid thoracoscope and fiberoptic bronchoscope for the treatment of spontaneous pneumothorax. Initially, we treated 31 of 79 patients with a rigid thoracoscope and electrocoagulation therapy. Therapy was effective in 17 (55 percent) of the patients. Only 13 (16 percent) of the 79 patients required a thoracotomy, which represents a 50 percent reduction in incidence. Of the 14 cases in which therapy was ineffective, the major cause of failure was our inability to view a broad thoracic area and treat all blebs with a rigid thoracoscope. Subsequently, we developed a method using a fiberoptic bronchoscope (FB), which allows an unrestricted view of the thoracic area, in combination with electrocoagulation and fibrinogen or thrombin solution (or both) for the treatment of spontaneous pneumothorax. We treated 19 of 39 patients with the FB method. Treatment was effective in 15 (80 percent) of the patients. Only 4 (10 percent) of the 39 patients required a thoracotomy, which is a reduction of over 60 percent in our original incidence. PMID- 1914611 TI - Step section preparation of transbronchial lung biopsy. Significance in the diagnosis of diffuse lung disease. AB - We retrospectively prepared step sections of nondiagnostic TBLB materials obtained from patients with diffuse or multiple lung disease and evaluated the diagnostic significance of the step section method. Among 112 patients with nondiagnostic TBLB findings, the preparation of step sections resulted in specific findings in seven cases. Step sections were especially useful for the detection of epithelioid granulomas and tumor tissue in patients with sarcoidosis and lymphangiosis carcinomatosa, respectively, but their contribution to the diagnosis of hypersensitivity pneumonitis, collagen-vascular disease, Mycoplasma pneumonia and pneumoconiosis was relatively small. In addition, step sections were useful for the detection of bronchiolitis obliterans affecting respiratory bronchioles. Overall, the examination of step sections was considered to be clinically useful in 30 cases (26.8 percent). Accordingly, the examination of step sections can be recommended before a further diagnostic procedure is chosen, if a TBLB performed in patients with diffuse or multifocal lung disease is nondiagnostic. PMID- 1914612 TI - Utility of pleural fluid analysis in predicting tube thoracostomy/decortication in parapneumonic effusions. AB - Recommended criteria for surgical drainage of parapneumonic effusions include evidence of frank purulence, a glucose level less than 40 mg/dl, a pH of less than 7.00, or an LDH greater than 1,000 IU/L. To test the utility of these criteria, we reviewed the three-year experience of three Rochester, NY, hospitals. We identified 133 patients undergoing thoracentesis for putative parapneumonic effusions. Of 91 patients with neutrophilic exudates, 43 met one or more criteria for tube thoracostomy: 48 did not. Twenty-one of the 43, including 9 with frank empyema, underwent immediate drainage. Of the 22 who did not, 11 eventually required tube thoracostomy and/or decortication. Of the 48 not meeting any of the criteria, 7 also came to surgery. Using whether the patients eventually underwent surgery as a measure of outcome, we calculated for those patients not undergoing immediate drainage the sensitivity, specificity, positive predictive values, and negative predictive values for each of the criteria. The four criteria have relatively high specificity ranging from 82 to 96 percent, but have low sensitivity varying from only 18 percent for a positive Gram stain to 53 percent for a fluid LDH greater than 1,000 IU/L. We conclude that these criteria have limited usefulness in predicting the need for eventual chest tube drainage/decortication. Patients not meeting the criteria require close follow-up as well. PMID- 1914613 TI - Effect of oxygen therapy on increasing arterial oxygen tension in hypoxemic patients with stable chronic obstructive pulmonary disease while breathing ambient air. AB - Recertification for long-term oxygen therapy (LTOT) has been recommended for patients who are clinically unstable when home oxygen therapy is begun. Periods of observation for clinical stability have ranged from three weeks to three months in large multicenter clinical trials. There is concern, however, that an increase in arterial oxygen tension occurring after three months may be related to the beneficial effects of oxygen rather than to continued changes in clinical stability. In a review of 20 patients receiving transtracheal oxygen (TTO2) therapy, it was found that four (20 percent) did not qualify for oxygen therapy at the end of six months because the PaO2 breathing ambient air had increased to levels above 55 mm Hg. All patients were clinically stable at the time of insertion of the transtracheal catheter and all had been receiving nasal oxygen for at least seven months (mean, 25.8 months) before entering the study. A retrospective analysis of data published by Weitzenblum et al disclosed that four (25 percent) of 16 patients had a similar increase in PaO2 when reexamined after one year of oxygen therapy. All of the patients had been studied at least one year before oxygen therapy was initiated and each had three consecutive arterial blood gas measurements done monthly to ensure clinical stability. The increase in PaO2 to levels above 55 mm Hg observed in patients receiving TTO2 therapy was associated with a reduction in alveolar-arterial oxygen gradient; however, arterial oxygen desaturation with walking persisted. The specific mechanisms for improvement in PaO2 during oxygen therapy require further study. Any recommendation for recertification of LTOT must recognize that an increase in PaO2 after three months may be due to the beneficial effects of the oxygen therapy and does not provide prima facie justification for termination of therapy. PMID- 1914614 TI - Factors associated with nightly variability in sleep-disordered breathing in the elderly. AB - The purpose of this study was to evaluate factors associated with nightly variability in sleep-disordered breathing. In this study, variability in sleep disordered breathing over two consecutive laboratory nights was evaluated in 71 aged volunteers with varying levels of sleep apnea. High variability (n = 13) and low variability (n = 58) groups were formed on the basis of an absolute two-night apnea/hypopnea index difference of a minimum ten events per hour. Results indicate high variability was related to longer soft palate measurements and the presence of nasal obstruction on physical examination. Within the high variability group, variation in sleep-disordered breathing occurred within identical gross body position over the two nights. The results suggest that local, anatomic factors affecting airway patency may not be constant from night to night. PMID- 1914615 TI - Superiority of live attenuated compared with inactivated influenza A virus vaccines in older, chronically ill adults. AB - Forty-eight older adults with chronic diseases were vaccinated intranasally with live attenuated influenza A/Korea/1/82 (H3N2), CR59 virus. Forty-two (88 percent) CR59 virus recipients became infected with vaccine virus without adverse effects or change in mean pulmonary function even among the 29 infected recipients with moderate to severe chronic obstructive pulmonary disease. Among control groups who received either monovalent or trivalent inactivated influenza virus vaccines intramuscularly, the rates of fourfold rises in serum antibody titer to hemagglutinin (HA) were not different from the rate following CR59 virus inoculation. However, CR59 virus was superior to inactivated virus vaccine at stimulating secretory antibody to HA. Vaccinees age 65 years and older were more likely to shed CR59 virus in nasal secretions than were younger vaccinees, but antibody responses were not different. CR59 virus vaccine was safe and immunogenic in this population and more often induced a nasal wash IgA antibody response than the inactivated virus vaccines. PMID- 1914616 TI - Etiology, treatment, and prognosis of large pericardial effusions. A study of 34 patients. AB - During the last 20 years, only a few studies have been published concerning large pericardial effusion. We recently reviewed 34 patients who presented with large pericardial effusion not associated with trauma. Our analysis revealed that half of the patients (52 percent) had pericardial effusion of unknown origin. Four patients had postmyocardial infarction pericardial effusion, three had associated malignant neoplasms, three suffered from collagen diseases, and two had infectious agents. Uremia and irradiation accounted for a single case each. Twenty-seven (79 percent) of the patients underwent pericardiocentesis and two (5.8 percent) had a pericardial window operation. The overall prognosis of the patients was excellent. PMID- 1914617 TI - Doppler echocardiography in 180 normally functioning St. Jude Medical aortic valve prostheses. Early and late postoperative assessments. AB - Limited Doppler echocardiographic data are available regarding velocities and gradients across normally functioning St. Jude Medical valves in the aortic position. To establish a standard reference for Doppler characteristics of normal aortic St. Jude Medical prostheses, we recorded continuous-wave Doppler measurements of peak and mean velocities and peak and mean gradients in 180 patients with normally functioning St. Jude aortic valves. There were 119 men and 61 women in the study; the mean age was 57 years. Minimal valvular regurgitation was present in 56 patients (31 percent). Velocities and gradients were reported in five patient groups according to valve sizes of 19 mm, 21 mm, 23 mm, 25 mm, and 27 mm; the mean gradients were 16 +/- 6, 16 +/- 6, 14 +/- 5, 12 +/- 5, and 12 +/- 6, respectively. Differences in velocities and gradients among the five valve sizes were not statistically significant (p = 0.05). Velocities and gradients were also analyzed in three patient groups according to time intervals after valve replacement. The first group (n = 64) underwent Doppler evaluation one to seven days postoperatively (mean, six days); the second group (n = 60) was evaluated after 8 to 30 days postoperatively (mean, 12 days); and the third group (n = 56) was evaluated after more than 30 days postoperatively (mean, 691 days). There were no significant differences in measurements for the three groups. PMID- 1914618 TI - Seismocardiography for monitoring changes in left ventricular function during ischemia. AB - Seismocardiography is a new noninvasive technique for recording cardiac vibrations. Changes in the recorded waves have been correlated with acute and chronic changes in left ventricular function. In this report, we describe a patient who developed ischemia induced by coronary angiography in the cardiac catheterization laboratory. The patient's seismocardiogram showed distinct changes during the ischemic episode that actually preceded the onset of symptoms and resolved after nitroglycerin therapy. The patient's seismocardiographic recordings were significantly different from the recordings from five control individuals. This observation suggests that seismocardiography may be helpful for monitoring left ventricular function during episodes of myocardial ischemia. PMID- 1914620 TI - Frequency spectra of normal breath sounds in childhood. AB - Clinicians who auscultate the chest of normal children note that the frequency content of their breath sounds appears to vary with age. Because these changes have not been systematically documented before, we recorded and analyzed inspiratory breath sounds in 35 children (0 to 13 years) and five adults (34 to 43 years). Our objective was to determine if the frequency content of normal breath sounds differed with age. Using a Fast Fourier Transform program, we calculated an average amplitude frequency spectrum from the inspiratory portion of the breath sounds of each subject (n = 10 breaths), and we compared the shape of the AFS and the values of selected frequency parameters. We found that the shape of the AFS of the youngest children differed most from the AFS of adults. Three of four selected frequency parameters (F25, F50, F95) differed significantly between children and adults (p less than 0.05), and one parameter (F75) did not (p = 0.11). The F25, F50, and F75 parameters of children (but not F95) were correlated (p less than 0.001) with increasing height and age. These results suggest that differences in the frequency content of the normal breath sounds of children and adults contribute to the differences that clinicians detect during clinical auscultation. PMID- 1914619 TI - Terfenadine effect on the bronchoconstriction, dermal response, and leukopenia induced by platelet-activating factor. AB - We have investigated the protective effect of oral terfenadine, a H1 antagonist, on the dermal and pulmonary response, and changes of circulating WBCs to injected and inhaled platelet activating factor. Nine men with mild asthma participated in a double-blind, crossover study using terfenadine, 120 mg, or placebo. Three hours after administration of study drug, pulmonary function was measured, and a PAF challenge was performed. Skin test to histamine and PAF was performed prior to study drug, and 2.5 hours after drug. Circulating WBC count was determined prior to PAF inhalation and during the PAF challenge. There was a significant improvement in pulmonary function on terfenadine. Terfenadine significantly inhibited the wheal and flare response to histamine and the flare response to injected PAF. Terfenadine did not have an effect on the change in circulating WBC count or the change in pulmonary function to inhaled PAF. These results suggest a limited role for endogenous histamine for the effects of PAF. PMID- 1914621 TI - Moms in jail. PMID- 1914622 TI - Object properties and knowledge in early lexical learning. AB - The ease with which young children learn object nouns suggests that they possess strategies to identify properties critical to lexical category membership. In previous work, young children used a same-shape criterion to extend new count nouns. The present research tested the generality of this shape bias. 2- and 3 year-olds were asked either to extend a novel count noun to new instances, or to choose unnamed objects to go together. The objects varied in shape, size, and texture. For half of the subjects, the objects had eyes--a property strongly associated with certain material kinds. If young children know this association, they should attend to texture as well as shape in classifying objects with eyes. With named objects only, both 2- and 3-year-old children classified eyeless objects by shape and objects with eyes by both shape and texture. The results suggest that very young children possess considerable knowledge about conditional relations between kinds of perceptual properties. Knowledge of such conditional relations may aid children in forming new categories and thus in discovering new word meanings. PMID- 1914623 TI - Longitudinal prediction of specific cognitive abilities from infant novelty preference. AB - A test of visual novelty preference, the Fagan Test of Infant Intelligence, was administered to a group of 113 full-term infants from the Colorado Adoption Project at 5 and 7 months of age. The infants were followed longitudinally and the Bayley scales were administered at 12 and 24 months, the Sequenced Inventory of Communication Development at 24 and 36 months, and the Stanford-Binet and the Colorado Specific Cognitive Abilities Test at 36 months. 1 novelty preference score was obtained for each infant by averaging across the 2 test ages. Novelty preference correlated significantly with 36-month Binet IQ, the first unrotated principle component from the cognitive battery, and the 24-month Bayley MDI score. Novelty preference was also compared to specific abilities at all 3 follow up ages; all of the specific abilities were significantly related to novelty preference, with the exceptions of 12- and 24-month Imitation and 36-month Perceptual Speed. Partial correlations suggest that novelty preference predicts language and memory independent of IQ. Overall, the results indicate that novelty preference during the first year of life not only predicts later IQ but may also reflect specific cognitive processes. PMID- 1914624 TI - Young children's adaptations to repeated separations from their mothers. AB - 80 infants, toddlers, and preschoolers were observed before, during, and after separations from their mothers, who were attending conferences (M duration = 4 days). Half the sample was separated only once and the other half experienced 3 separations across a 6-month period. The study was designed: (a) to determine how separations affect children's behavior when there are no changes in the family constellation as there typically are during other separations, such as the birth of a new child, and (b) to determine the effects of repeated separations. Fewer changes in sleep and play behaviors suggested that this type of separation was less stressful than separations for the birth of another child. Nonetheless, the separations were still stressful, but principally for the single-separation group. In that group, changes were noted in both play and sleep behaviors. Following reunion, their sleep behaviors and more sophisticated play behaviors returned to baseline. However, activity level and the more insecure behaviors, such as wandering aimlessly, watching other children play, and interacting with their teachers, remained elevated following the mother's return. The multiple separation group, in contrast, showed only 1 behavior change during their third separation, i.e., reduced interactions with their peers during the separation period, which returned to baseline following reunion. Repeated-measures analyses of the first and third separations of the multiple-separations group suggested that only the first separation was stressful. Thus, the infants and children in this study seemed to adapt to repeated separations. PMID- 1914625 TI - Are insecure-avoidant infants with extensive day-care experience less stressed by and more independent in the strange situation? AB - In order to test the hypothesis that elevated ratings of avoidance and classifications of insecure-avoidant attachments of infants with extensive infant day-care histories may be the result of the fact that children with routine experiences of separation are less stressed by, and more independent in, the Strange Situation than more traditionally reared infants, 2 groups of 12-month old infants with insecure-avoidant attachments were compared on 2 behavioral indices in each reunion-with-mother episode of the Strange Situation. 9 infants experienced less than 20 hours per week of nonparental care in their first year, and 11 infants experienced 20 or more hours of care. Contrary to propositions advanced by Clarke-Stewart, Thompson, and others, insecure-avoidant infants with extensive nonparental care experience whimpered, fussed, and cried more and engaged in object play less in each reunion episode than their insecure-avoidant counterparts with less nonparental care experience. These results are discussed in terms of the recent controversy surrounding infant day-care in the United States. PMID- 1914626 TI - Effect of maternal social support on attachment: experimental evidence. AB - The present study used an experimental format to evaluate the influence of maternal social support on the development of attachment. 46 WIC primigravidas were randomly assigned to an experimental or control condition. Volunteer coaches, trained to provide maternal support and information, met with experimentals prenatally and during the first postpartum year. Experimentals and controls did not differ on demographics, ego level, verbal ability, affect, or perceived social support. At 14 months, experimental infants scored higher on an Attachment Ratings cluster from Waters and Deane's new Q-sort procedure. This cluster was more sensitive than a Criterion Sort measure in detecting the effect of the manipulation and as or more sensitive to maternal affect, perceived support, and the HOME. These findings provide experimental evidence regarding the importance of social support on infant attachment and support for an alternative approach for reducing data from the attachment Q-sort. PMID- 1914627 TI - A two-year longitudinal study of stressful life events, social support, and social problem-solving skills: contributions to children's behavioral and academic adjustment. AB - We investigated the contributions of stressful life events and resources (social support and social problem-solving skills) to predicting changes in children's adjustment. At Time 1, 361 third through fifth graders completed measures of social support and social problem-solving skills. Their parents completed a stressful life events scale and a child behavior rating measure. The children's teachers provided ratings of behavioral and academic adjustment. 2-year follow-up data (Time 2) were obtained for approximately half of the sample on the same measures. Time 1 stressful life events and resources showed some significant but modest zero-order correlations with the Time 2 adjustment indices. Hierarchical multiple regressions revealed prospective effects for Time 1 social support on later teacher-rated competencies and grade-point average. In addition, increases over time in social support and social problem-solving skills (a composite score) were significantly related to improvement in behavioral and academic adjustment, whereas stressful life events were not predictive of adjustment. PMID- 1914628 TI - Vulnerability and resilience: a study of high-risk adolescents. AB - Factors that allow children to maintain socially competent behaviors despite stress were examined among 144 inner-city ninth-grade students with a mean age of 15.3 years. Stress was operationalized by scores on a negative life events scale, and definitions of social competence were based on peer ratings, teacher ratings, and school grades. Moderator variables examined included intelligence, internal locus of control, social skills, ego development, and positive life events. Following theoretical models by Garmezy and Rutter, distinctions were made between compensatory factors (which are directly related to competence) and protective/vulnerability factors (which interact with stress in influencing competence). Ego development was found to be compensatory against stress. Internality and social skills proved to be protective factors, while intelligence and positive events were involved in vulnerability processes. This study also revealed that children labeled as resilient were significantly more depressed and anxious than were competent children from low stress backgrounds. PMID- 1914630 TI - Burn management and research in China. PMID- 1914629 TI - Observations of parent reactions to sex-stereotyped behaviors: age and sex effects. AB - To examine differential socialization of boys and girls by mothers and fathers, home observations were completed for families of 92 12-month-old children, 82 18 month-old children, and 172 5-year-old children. Mothers gave more instructions and directions than did fathers, while fathers spent more time in positive play interaction. Differences in parents' reactions to 12- and 18-month boys and girls were as expected, with the exception that boys received more negative comment for communication attempts than did girls. The suggestion in the literature that fathers would be more involved in sex typing than mothers was not confirmed in this study. The only 2 significant sex-of-parent x sex-of-child effects occurred at 18 months; fathers gave fewer positive reactions to boys engaging in female typical toy play, and mothers gave more instruction to girls when they attempted to communicate. We argue that the second year of life is the time when children are learning many new skills and when parents are still experimenting with parenting styles and may well use stereotypical responses when unsure of themselves. PMID- 1914631 TI - Biomechanical evaluation of cervical spine instability after multiple level laminectomy. AB - Four fresh human cervical spine specimens (C2-T1) were tested both intact and with C5-C6 laminectomies to evaluate the biomechanical effects of multiple level laminectomy. The loads applied to the specimens were physiological and clinically relevant motion patterns were simulated. The results showed that C5 vertical displacements increased by 83.33% in axial compression, 168.75% in flexion, 106.09% in extension, and 35.14% in left bending after C5-C6 laminectomies compared with intact specimens. The increased rates of C6 vertical displacements after laminectomy were slightly lower than C5. The anterior horizontal bulging of C5-6 discs increased by 29.69% in axial compression, 13.86% in flexion, 61.79% in extension, and 13.40% in left bending after laminectomy. The rotational angles of whole specimens had an increase of 15% after laminectomy. The strains in the anterior vertebral bodies and posterior laminae near the articular processes of C5 and C6 were increased significantly after laminectomy. The data indicated that multiple level laminectomy can lead to biomechanical instability of the cervical spine. PMID- 1914632 TI - Transcoronary ethanol ablation of experimental ventricular tachycardia after epicardial ice mapping and localizing. AB - Thirty-seven reproducible ventricular tachycardias (VTs) were induced in 19 dogs after the onset of myocardial infarction. The site of origin of VT was localized in 19 (59%) of 32 VTs by ice epicardial mapping. After 0.3-1.2 ml of 95% ethanol was injected into a small coronary artery supplying the arrhythmogenic area, VT was no longer inducible in 10 of 14 dogs. Intramyocardial ethanol (1-3 ml) was injected into the site of origin of VT in 9 dogs including 4 with VTs reinduced after intracoronary ethanol. Six of these VTs were not reinduced. Thus, the total efficacy rate was 84%. In 7 dogs, after injection of 0.4-1.2 ml (mean 0.5 ml) of 95% ethanol into a small normal coronary artery, the extent of the changes in ECG, CK-MB and pathology was found to be related to the size of myocardial damage and to the dose of ethanol. The smaller the dose of ethanol was given and the more distal the branch of coronary artery into which the ethanol was injected, the smaller the myocardial damage was. The data demonstrated that intracoronary or intramyocardial injection of ethanol may ablate the experimental VT induced by programmed heart stimulation in dogs after myocardial infarction, indicating that this approach may be useful and meaningful in some selected instances. However, it is necessary to limit the myocardial damage as far as possible. PMID- 1914633 TI - The 1958 and 1987 ARA revised criteria for rheumatoid arthritis in Chinese patients. A comparative study. AB - The American Rheumatism Association (ARA) 1958 and 1987 criteria for the classification of rheumatoid arthritis (RA) were applied to 111 consecutive RA patients and 54 patients with non-RA connective tissue diseases from three hospitals of tertiary level in Beijing. Comparison of the two criteria showed that the specificity was the same, being 88% for both, whereas the sensitivity varied from 94% of the 1958 criteria to 91% of the 1987 criteria. Factors affecting the sensitivity were morning stiffness for more than one hour and increase of number of swollen joints from one to three in the 1987 revised criteria. PMID- 1914634 TI - Elimination of malignant clonogenic cells from human bone marrow using multiple myeloid cell-specific monoclonal antibodies and complement. AB - Single or combined monoclonal antibodies (McAbs) Zh53, Zh820, and Zh2-1 have been used to eliminate malignant clonogenic cells from human bone marrow. The test of cytotoxicity showed that all of these McAbs could express high specific cytotoxic action against HL-60 cells and were selectively complement-dependent cytotoxic to various types of fresh leukemic cells. Clonogenic assay detected that single treatment with antibody and rabbit complement (RC) could reduce clonogenic units of HL-60 cells by more than 2 logs and two treatments reduced clonogenic units by more than 4 logs. However, combination of 2 McAbs could reduce clonogenic units by 4-5 logs. The data suggest that multiple treatments with McAbs and RC or a combination of 2 McAbs are more effective than a single treatment in eliminating clonogenic tumor cells. Treatment of normal human bone marrow with Zh53, Zh2-1 and RC did not produce a loss of normal CFU-GM, but treatment with Zh820 reduced the clonic units of normal CFU-GM by 24%. PMID- 1914635 TI - Comparative evaluation of nine different methods for detecting enterotoxin of Escherichia coli. AB - Nine different methods for detecting enterotoxin of Escherichia coli were studied and compared. We found rabbit ileal-loop test and suckling mouse assay were both quite accurate and reliable for detecting heat labile toxin (LT) and heat stable toxin (ST) of enterotoxigenic Escherichia coli (ETEC). Mouse ileal-loop test was simple, but its sensitivity and specificity were comparatively low. CHO cell culture assay might be more sensitive and specific. LT-DNA probe was the most sensitive and specific method. In practical application, PIHT (plate immunohemolytic test), Biken's, SPA-CoA and ELISA methods are recognized as simple, rapid, sensitive and specific methods for detecting ETEC-LT. These methods can be selected for use in clinical laboratory. PMID- 1914636 TI - Experience with bromocriptine for the treatment of female infertility due to hyperprolactinemia. AB - From July 1981 to September 1988, 106 infertile patients with hyperprolactinemia treated with bromocriptine were reviewed retrospectively with special attention to the dosage of bromocriptine and the evaluation of infertility before treatment. 84 patients (79.2%) became pregnant. The 106 patients were divided into 3 groups according to the following doses: 7.5, 5.0, and less than 5.0 mg/day. The pregnancy rate was 90.7%, 84.6%, and 66.7% respectively with the highest at 7.5 mg/day, which was significantly higher than that at less than 5.0 mg/day (P less than 0.02). The average duration from treatment to pregnancy was 3.6, 3.4 and 7.4 months respectively. The longest duration in the less than 5 mg/day group was twice that in the other two groups. 85% of the pregnancies occurred within 6 months of treatment. Pretreatment of organic lesions and additional therapy for induction of ovulation were given to 29.8% of the pregnancies. The causes of infertility other than hyperprolactinemia were evaluated systemically before the use of bromocriptine. The optimal dose was 5 7.5 mg/day. Macroprolactinomas can be treated with bromocriptine, but should be followed up closely for the development of symptoms of intracranial pressure during pregnancy. PMID- 1914637 TI - Special spectacles facilitating debridement. Report of use in 300 cases. AB - According to the difference of light reflection of tissue with different degree of viability, spectacles were made from glass permitting light of certain wavelength to pass to help distinguish viable from nonviable tissue. They were used in debridement of wounds in 300 patients. The results showed that the quality of debridement was improved as evidenced by better healing and shorter healing time. These spectacles were helpful, especially for young and unexperienced operators to distinguish viable from nonviable tissue. They were also used to predict flap viability in plastic surgery. PMID- 1914638 TI - Stroke in urban and rural areas of China. AB - A large-scale population survey was conducted to clarify the degree of harm and feature of distribution of stroke in China. 5 800,000 of a billion people were investigated in 29 provinces and cities excluding Taiwan province. The incidence, prevalence and mortality were standardized by direct method using the world standard population. The incidence of stroke was 109.95 per 100,000 people in 1986 and its 95% CI (confidence interval) 107.25-112.65 per 100,000. The age standardized incidence was 115.87/100,000. The point prevalence of stroke was 245.49 per 100,000 people on December 31, 1986 and its 95% CI 241.57-249.61 per 100,000, with an age-standardized prevalence of 259.86 per 100,000. The mortality of stroke was 76.78 per 100,000 in 1986 and its 95% CI 74.52-79.04 per 100,000, with an age-standardized mortality of 80.94 per 100,000. There was a tendency for the rates to increase gradually from south to north and to decrease progressively from east to west. The models of linear regression were established between latitude and rates as well as between longitude and rates. The incidence, prevalence and mortality of stroke differed significantly in various topographic areas. They were much higher in cities than in rural areas, and much higher in men than in women. The incidence, prevalence and mortality increased with age, and their relationships fitted in Logistic curve well. PMID- 1914639 TI - [The legal importance of immediate pain in injection errors]. PMID- 1914640 TI - [Differential diagnostic classification of lymphomas in the gastrointestinal tract]. PMID- 1914641 TI - [Surgical treatment of gastrointestinal lymphomas]. PMID- 1914642 TI - [The value of chemo- and radiotherapy in gastrointestinal lymphomas]. PMID- 1914643 TI - [Dyspepsia and food intolerance in symptomatic gallstone disease. Does cholecystectomy help?]. AB - 60 patients with symptomatic gallstone disease were asked about their abdominal symptoms and food intolerance. Equally a healthy control group was investigated. Preoperatively, 72% of patients with gallstones suffered from right upper quadrant pain. Additionally all patients complained of associated dyspeptic symptoms (100% vs. 8% of the control group). 51% of patients with gallstone disease vs. 15% of the control group avoided flatulent and fatty food. 4 months after cholecystectomy, 90% were painfree, 82% were free of dyspeptic symptoms and 84% were not complaining of any food intolerance. 6% developed new food intolerances. Thus cholecystectomy seems to be an effective treatment, not only for typical gallstone related symptoms, but also for associated symptoms, such as dyspepsia and food intolerance. Different therapeutic regimens have to compete with these results. PMID- 1914644 TI - [Trans-sternal thymectomy in myasthenia gravis]. AB - Between 1986 and 1989 27 patients with myasthenia gravis underwent radical thymectomy: 24 patients without and two patients with thymoma through a trans sternal incision, another with thymomatous myasthenia through a left-sided thoracotomy. The patients were staged according to the modified Ossermann classification. The results were evaluated prospectively according to the Disability Status Scale of Oosterhuis. During a mean follow up of 22.4 months, 21 patients (77%) benefited from the operation with complete remission achieved in 9 (33%) and significant improvement noted in 12 (44%). There were no operative deaths and no hospital morbidity. The mean operation time was 88 minutes, the mean postoperative hospital stay 10.5 days. These results support the recommendation for radical trans-sternal thymectomy in the treatment of patients with myasthenia gravis as a safe procedure. PMID- 1914645 TI - [Fibrin-coated collagen fleece in thoracic surgery. Initial clinical experience]. AB - After resecting procedures to the parenchyma of the lung the resection site was sealed with a collagen vleece combined with fibrin glue in 26 patients. No patient exhibited rebleeding. An air leak was present up to the first postoperative day in 19 patients, up to the third postoperative day in 5 patients. In two patients, duration of air leak extended beyond the third postoperative day, this was defined as therapeutic failure. The use of collagen vleece combined with fibrin glue represents a valuable contribution in thoracic surgery. PMID- 1914646 TI - [Incidence of lung embolism before and after thrombectomy of deep leg and pelvic vein thrombosis]. AB - According to scintigraphic and pathological studies, pelvic and thigh venous thrombosis led to pulmonary embolism in 50-60% of all cases. After thrombectomy, an incidence of 1% is reported, when assessed only clinically. In 29 patients with acute pelvic or thigh venous thrombosis, perfusion scintigraphic lung scans were performed immediately before operation and on day 1 or day 2 postoperatively. In 7 patients (24.1%) preoperatively and 12 patients (41.4%) postoperatively, segmental perfusion defects indicating pulmonary embolism were demonstrated. Thus the incidence of pulmonary embolism according to thrombectomy is much higher than previously suspected. PMID- 1914647 TI - [The value of classification for therapy and prognosis of acute pancreatitis. Analysis of a patient sample of the Heidelberg Surgical University Clinic 1986 1989]. AB - 116 patients admitted for acute pancreatitis were analysed. In 80% of patients presenting biliary pancreatitis cholecystectomy and bile duct exploration was the prevalent treatment, in 7.8% pancreatic necrosis was removed. Indications to operate on patients with non-biliary pancreatitis included enhancement of pancreatic inflammation revealed by computed tomography and multi-organ-failure or sepsis complicating the course of the disease (incidence of laparotomy 20.3%, incidence of necrosectomy 12.3%). According to this concept 2 out of 3 patients presenting partial pancreatic necrosis recovered without operation. Lethality of patients with acute necrotizing pancreatitis (6.9%) was accounted 25%, over-all mortality 6%. Methods used for classification of severity of acute pancreatitis (Mainz classification, Ranson criteria) turned out to be not reliable. Clinical staging of pancreatitis was not in accordance with intraoperative findings in 51.9% of cases. As a prerequisite for stage-dependent therapy new objective data to access severity and clinical course of acute pancreatitis have to be worked out. PMID- 1914648 TI - [Gastrointestinal amyloidosis: differential diagnosis and indications for surgical therapy]. AB - The diagnosis of gastrointestinal amyloidosis may be difficult for both the radiologist and the examining surgeon because clinical symptoms are often uncharacteristic. Upper gastrointestinal series may show stenosing submucosal masses in the esophagus or gastric antrum with diminished peristalsis and pliability mimicking malignancies. With small bowel involvement, diminished motility and segmental or complete distension, a prolonged transit time, and eventually obstruction are common findings. In the present study, we report four cases of gastrointestinal amyloidosis and review the indications for operative treatment. Surgery should be avoided for abdominal pseudo-obstruction and but may be indicated in patients with gastrointestinal bleeding, perforation or other severe complications. The postoperative course is characterized by impaired wound healing, a high rate of heart and kidney failures, and considerable perioperative mortality. Thus, results are frequently unsatisfactory. PMID- 1914649 TI - [Ruptured aneurysm of the splenic artery in alpha 1-antitrypsin deficiency with liver cirrhosis and portal hypertension]. PMID- 1914650 TI - [Aneurysm of the gastroduodenal artery with aplasia of the celiac trunk]. PMID- 1914651 TI - [A summary of the national seminar on neonatal asphyxia and hysterectomy]. PMID- 1914652 TI - [Early diagnosis of fetal distress and neonatal asphyxia]. AB - 122 cases of high risk pregnancies, consisting of mainly pregnancy-induced hypertension (PIH), medical complications, postmaturity and suspected distress were periodically monitored with 11 biophysical and biochemical assays. Positive prediction accuracy rate was analyzed with a neonatal UA pH less than 7.20 as the criterion of fetal hypoxia and ischemia. A number of predicting items together, namely: NST, the other Manning's 4 items, internal monitoring with abnormal Cardiotocography, meconium deeply stained amniotic fluid, FBS pH less than 7.2, uterine contraction time lasting greater than 37 sec and interval shorter than 70 sec, gave the best sensitivity, specificity, positive and negative prediction rates and total accuracy rate of 71.69%, 84.06%, 77.55%, 79.45% and 78.68% respectively. The causes for false positive and false negative cases were discussed. Special attention must be paid to those cases with low UA pH al though normal Apgar scores during the neonatal period. PMID- 1914653 TI - [Correlation between neonatal Apgar scores and the results of maternal and umbilical cord blood gas analysis]. AB - The correlation between the Apgar scores of 162 neonatal 1 minute after birth and the result of maternal arterial and umbilical cord blood gas analysis was studied. The results were as follows: (1) With decreasing neonatal Apgar score, the value of the pH, PO2, HCO3, TCO2 and actual base excess (ABE) of the maternal arterial and umbilical cord blood also decreased markedly, while the PCO2, except that of the maternal arterial blood, increased obviously, and mixed acid base imbalance and hypoxemia also significantly increased (P less than 0.01). (2) Of the neonates with umbilical arterial blood pH less than or equal to 7.2, the proportion of neonates with Apgar score less than or equal to 3 amounted to 100%; that with on Apgar score of 4-7, was 77.7%; And that with on Apgar score of 8-10, was 56.31%. The difference was highly significant statistically (P less than 0.01). PMID- 1914654 TI - [Early diagnosis and prevention of hypoxic and ischemic encephalopathy and intracranial hemorrhage]. AB - 161 cases of newborn with history of perinatal hypoxic and clinical neural symptoms were intensively monitored by real-time ultrasound and clinical examination. Hypoxic and ischemic encephalopathy (HIE) and intracranial hemorrhage (ICH) were diagnosed in 44 cases. The incidences of HIE and ICH were 2.39 per 1,000 livebirths and 42.67 per 1000 cases of neonatal asphyxia or 12.7 per 1000 cases of fetal distress. The high risk factors contributing to HIE and ICH were investigated along with maternal complications during pregnancy and labor, neonatal complications and types of anoxia. The value of real-time ultrasound in the diagnosis of HIE and ICH was discussed. Early diagnosis and prediction of HIE and ICH were speculated upon. PMID- 1914656 TI - [Improved technics in 578 abdominal total hysterectomies]. AB - This paper reports the improved technics in 578 abdominal total hysterectomies. After dividing the infundibulo-pelvic ligaments and both layers of the broad ligaments the ovarian vessels were dissected out, cut and ligated, the utero sacral ligaments revered but not ligated, and if necessary, the bleeding points were tied. After cutting the intervening tissues on both sides of the uterus, the uterine vessels could be identified, clamped and ligated at level below the cervical internal os. The cut edges of the vaginal cuff had to be approximated exactly, avoiding too close and too tight sutures. There was no organ injured during the operations, no abdominal pain nor hemorrhage from the cut edge of vaginal cuff after operation. Of the 520 patients followed up after operation, 518 cases had good healing at the vaginal stumps with granulation in only 2 cases, the effect with this improved method of hysterectomy has been considered satisfactory. PMID- 1914655 TI - [Desirable temperature in the operating room during neonatal resuscitation]. AB - 30 naked and untouched neonates, delivered by cesarean section, were studied at room temperature of 23.97 +/- 1.73 degrees C, and moisture of 77.30 +/- 6.95% for 5 minutes. At the end of this period, the anal temperature (core temperature) lowered by 0.70 +/- 0.55 C. The data were analysed and a linear regression equation was set up with help of TSP software in IBM-PC computer. The value for core temperature decrease (W) = 3.089-0.081Q (room temperature). The coefficient of the regression equation (0.081) was found to be significant according to t test table. This study showed that the appropriate room temperature for naked and untouched neonates is 37-38 degrees C. Therefore, the author suggests that the synthetic measures of heat preservation be taken according to the needs of neonates, as well as parturients and medical staff. PMID- 1914657 TI - [An analysis of 749 cases of surgical treatment of uterine myomata]. AB - There were altogether 749 cases of uterine myomata verified surgically and pathologically in our hospital, in 1985 through 1989, amounting to 10.8% of all the patients admitted to the gynecological ward in the same period of time. All of them had operation varying according to the tumor site, size, number, complication, if present or whether preservation of fertility was desired. These included intraperitoneal total hysterectomy, vaginal total hysterectomy, myomectomy, extraperitoneal hysterectomy, combined vaginal, and abdominal routes for resection of submucous myoma, etc, altogether 7 kinds of operative procedures. Post operative complications rate was 1.1%. It is thought that the therapeutic result and long term outcome are closely related with the choice of operative procedures. PMID- 1914658 TI - [Analysis of hysterectomies in 118 obstetric cases]. AB - During a period of 36 years, the rate of hysterectomy was 0.054% of all obstetric patients in our hospital, 0.0446% of cesarean section cases, and 0.005% of vaginal deliveries respectively. From 50 s to 80 s, the cesarean section rate greatly increased while the hysterectomy rate in parturition decreased. The indications for cesarean hysterectomy change from ruptured uterus, abruptio placenta and intrapartum infection to uterine atony highly increased placenta or myoma of the uterus. Cesarean hysterectomy rate due to splitting of uterine wound after cesarean section highly increased in 80 s. Bleeding for more than 1,000 ml during operation accounted for 62.7% of them. However, operative complication rate reached to 11.8%. To reduce cesarean hysterectomy rate, we suggest emphasizing maternal health care, use of uterine packing to lessen bleeding and careful management of operation as important means for reducing uterine incision wound splitting after cesarean section. PMID- 1914659 TI - [Systemic control in rural perinatal health care ("Triple Ten Management")]. AB - Using "Triple Ten Management" as the basic method, we conducted research on a standard model of rural perinatal health care in our province. The "Triple Ten Management" includes: (1) controlling ten commonest high risk pregnancies; (2) application of ten perinatal monitoring techniques; (3) ten concerted managing regimes of rural perinatal care. Being verified in test points of 38 townships in 13 counties for one year, the model has been proved to be suitable for rural status and effective. The maternal mortality of the test points was reduced from 6.11/10,000 to 3.58/10,000; the perinatal mortality from 22.18% to 18.44% and the incidences of eclampsia and neonatal tetanus were also significantly reduced. PMID- 1914660 TI - [Use of amniotic drop-volume determination in estimating fetal lung maturity]. AB - The value of amniotic fluid drop-volume determination with a self-made Fetal Lung Maturity Apparatus in the analysis of fetal lung maturity is studied with 148 samples. The results were compared with those of L/S ratios, it shows that this method has a sensitivity of 95%, specificity 91% and accuracy 93%, if a falling drop-interval of less than or equal to 85 seconds was taken as the defining point for lung maturity. The mean falling drop-interval was 89.0 +/- 12.3 seconds in the 18-30 th week pregnancy samples, 72.7 +/- 9.4 seconds in the 36-42 nd week samples and 81.4 +/- 9.9 seconds in the 31-35 th week samples. (P less than 0.001). The effects of blood and meconium on the testing were also studied. The drop-volume test is recommended as an accurate, rapid and easy method in predicting fetal lung maturity. PMID- 1914661 TI - [CA125 and radioimmunoimaging in monitoring of epithelial ovarian carcinoma]. AB - Serum CA125 was measured by monoclonal antibody-OC125 in 50 primary and 29 suspected recurrent ovarian cancer patients. Among the later, RII examination by using 131I labelled polyclonal antibody-OCOV3 was carried out in 16 cases at the same time. For the suspected recurrent cases, the results, as checked by surgico pathological findings, revealed a corroborative rate of 79.3% for CA125 assay and 87.5% for RII technique. The positive predictive value of both CA125 assay and RII were 100%, while the negative predictive value was only 25% for CA125 assay and 50% for RII technique. However, for each individual case if the results of the two tests were combined, the negative predictive value was also 100%. Preoperative CA125 level had no significant relationship with the prognosis in primary cases. But the two year survival rate for recurrent cases with a preoperative CA125 less than or equal to 35,000 U/L was much higher than those with CA125 greater than 35,000 U/L. PMID- 1914662 TI - Cell cycle control of initiation of eukaryotic DNA replication. AB - Eukaryotic DNA replication is confined to a specific portion of the cell cycle (the S phase) and is highly regulated: every segment of the genome is replicated once per S phase, but no segment is normally replicated more than once. How this tight control of replication is accomplished is not known. However, the pace of research into the mechanisms of eukaryotic DNA replication and of cell cycle control has accelerated dramatically within the past few years. Recent investigations provide, for the first time, hints of how control of replication may be coupled at the molecular level to control of the cell cycle. This review is intended to bring these recent investigations to the reader's attention and to speculate about their relationships to each other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914663 TI - Developmental changes in fat body and midgut chromosomes of Drosophila auraria. AB - Changes in puffing activity of fat body (FB) and midgut (MG) chromosomes of Drosophila auraria during late larval and white prepupal development as well as after in vitro culture with or without ecdysterone were studied and compared with those of the salivary gland (SG). The Balbiani Rings characteristic of the SG chromosomes of D. auraria, are not formed in FB and MG. Most of the inverted tandem chromosomal duplications that have been found to be common to all three tissues showed differentiation of puffing activity of the bands considered to be homologous. The major early ecdysone puffs 73A and 73B (considered to be homologues of D. melanogaster puffs 74EF and 75B, respectively), together with other early ecdysone puffs were present in all three tissues. Clear intermoult and postintermoult puffs were not evident in FB and MG chromosomes. However, a small set of late ecdysone puffs could be scored in FB, while no late ecdysone puffs were abserved in MG. Other tissue-specific puffs were identified, but a very small number of them were limited to MG. PMID- 1914664 TI - Cytogenetic and molecular aspects of position effect variegation in Drosophila. III. Continuous and discontinuous compaction of chromosomal material as a result of position effect variegation. AB - Variations in compaction of chromosomal material of the rearrangements Dp(1;f) 1337, Dp(1;f) R, Dp(1;1)pn2b, and T(1;4)wm258-21, which display an extended position effect, were characterized. Morphological changes found in these rearangements were assigned to two major types: (i) continuous compaction, in which bands and interbands located distal to the eu/heterochromatin junction fuse into one compacted block of chromatin. The extent of compaction is increased by enhancers of position effect (low temperature, removal of the Y or 2R chromosome heterochromatin). In extreme cases compaction extends over dozens of bands. (ii) Discontinuous compaction, in which at least two zones of compaction separated by morphologically normal zones can readily be identified. As a result, some regions located at a greater distance from heterochromatin may be compacted more frequently than others that map nearer to it. A few regions (1D, 2B1-12, 2D) were shown to be most frequently compacted in all rearrangements investigated. The 2B13-18, 2C1-2, 2E, and 2F regions exhibited the lowest frequencies of compaction. Compaction of the zone containing the 2B1-12 bands is always accompanied by inactivation of the ecs locus, which maps in the 2B3-5 puff. At the same time the 2C1-2 and 2E bands located nearer to the breakpoint can retain normal morphology and puffing in response to ecdysterone. The results are interpreted as morphological manifestations of the discontinuity of the spreading effect. PMID- 1914665 TI - [Electrogastrography: the clinical significance of changes during fasting and postprandial state]. AB - Surface electrogastrograms were recorded in 95 patients. There were 6 groups of patients: chronic superficial gastritis (20), chronic atrophic gastritis (20), duodenal ulcer (20), gastric ulcer (17), gastric cancer (8), and diabetes mellitus (10). Electrogastrographic examination was continuously carried out for 60 minutes both in fasting and postprandial state. (1) During the fasting state, in 72% of the cases, there was a 50% to 100% change in the mean of the amplitude among six 10-minute periods of recording. (2) In 23 cases (25%), there was no amplitude increase in the postprandial electrogastrogram. Feeding caused an increase in amplitude by 30-240 microV over the prefeeding state in 70 cases (75%). (3) The distribution of amplitude in various groups of disease overlapped each other. The difference in amplitude or frequency would not be used as a diagnostic parameter of gastric diseases. (4) Tachygastria of 5-7.3 cycles per minute was observed in 15 of the 95 patients. The longest episode was a wave with 7.3 cycles per minute lasting for 20 minutes. It is difficult to evaluate the clinical significance of the observed tachygastria. PMID- 1914666 TI - [Duodenal ulcer disease: Helicobacter pylori and hyperchlorhydria]. AB - Basal and pentagastrin-stimulated gastric acid secretion and basal serum gastrin level were investigated in 55 active duodenal ulcer patients with antral colonization with Helicobacter pylori (HP) and 17 patients without. Our study shows that basal (BAO) and pentagastrin-stimulated gastric acid secretion (MAO and PAO) were significantly higher in HP positive than in HP negative patients with duodenal ulcer disease. There were also a tendency to increase in basal serum gastrin concentration in HP positive patients. We suggest that antral HP increases antral gastrin release and gastric secretion. Increased acid secretion then causes duodenal ulcers by producing a low intraduodenal pH. PMID- 1914668 TI - [Gastric elimination research on patients with gastric disease]. AB - Liquid elimination function of the stomach was studied in 41 patients and 9 normal subjects by using SPECT technique. The result suggested that six kinds of the liquid elimination curve of stomach can be classified. Patients with chronic gastritis and peptic ulcer mostly were kinds of slow elimination (1) and (2). Normal subjects mostly were kind of (6). The pathophysiologic significance of six kinds liquid elimination pattern needs further research. PMID- 1914667 TI - [A study on motility of sphincter of Oddi in postcholecystectomy syndrome]. AB - Endoscopic manometry of sphincter of Oddi (SO) and serum levels of gastrin, glucagon, and somatostatin were measured in patients with postcholecystectomy syndrome (n = 12), asymptomatic cholecystectomy patients (n = 6), and controlled subjects (n = 14). Pentagastrin-stimulated gastric acid secretion test was also performed in part of patients who had symptoms or no symptoms after the removal of gallbladder. The results showed that the patients of symptomatic group had hypertonic dyskinesia of SO as shown by deep and wide waves superimposed on high basal pressure plateau of SO. The symptomatic group also had a higher serum level of gastrin and a greater BAO than those of other two groups. No difference of serum levels of glucagon and somatostatin was found among these three groups. The hypertonic dyskinesia of SO and hypergastrinemia are possibly important factors in the pathogenesis of postcholecystectomy syndrome. PMID- 1914669 TI - [A survey on eight patients and one family history of Peutz-Jeghers syndrome]. AB - Eight patients with Peutz-Jeghers Syndrome (PJS) have been diagnosed by fiber light colonoscope in recent ten years in our hospital. Four of them coming from the same family. It was called "Gao family". We made a survey on 42 members in 5 generation of the family including 13 definite patients and 3 suspicious patients. The specification of PJS, the malignant change of polyps and the misdiagnosis of hamartoma are discussed in this paper. PMID- 1914670 TI - [The characteristics of right ventricular function in patients with essential hypertension]. AB - Two-dimensional and pulsed Doppler echocardiography were used to evaluate the function of right ventricule in 166 patients with essential hypertension and the results were compared with those of 79 normal subjects. The pulmonary artery peak flow velocity in 100 patients without left ventricular hypertrophy (LVH) had no significant difference with that of normal controls (0.65 +/- 0.17 vs 0.63 +/- 0.18, P greater than 0.05). The tricuspid early peak flow velocity (E) decreased (0.43 +/- 0.08 vs 0.46 +/- 0.12, P less than 0.01) but the late peak flow velocity (A) increased (0.30 +/- 0.09 vs 0.24 +/- 0.06, P less than 0.001). E/A reduced also (1.57 +/- 0.53 vs 2.02 +/- 0.78, P less than 0.01). The pulmonary peak flow velocity in 66 patients with LVH elevated markedly as compared with those without LVH (0.71 +/- 0.18 vs 0.65 +/- 0.17, P less than 0.001), A increased (0.34 +/- 00.10 vs 0.30 +/- 0.09, P less than 0.001) and E/A decreased (1.29 +/- 0.37 vs 1.57 +/- 0.53, P less than 0.001). The decrement of E/A correlated with the thickness of interventricular septum and the left ventricular mass (r = -0.68 and -0.60 respectively, P less than 0.01). The results show that the diastolic function of right ventricule was damaged in the early stage of essential hypertension but the systolic function remains unchanged. The diastolic function decreased and the systolic function increased further concomitantly with the development of LVH. PMID- 1914671 TI - [An analysis of 30 cases of chylothorax and chyloperitoneum]. AB - Thirty patients diagnosed as chylothorax and chyloperitoneum (13 of chylothorax, 9 of chyloperitoneum and 8 of both) in PUMC Hospital from 1923 to 1989 were reported. Thus, the incidence rate of these two diseases is rather low. The commonest causes were iatrogenic trauma (9 cases) and malignant tumor (7 cases). Other causes were tuberculosis (5 cases), lymphangioma (2 cases), Behcet's syndrome (1 case) and non-iatrogenic trauma (1 case). The etiology was not known in 5 cases. Acute episode was observed in patients with traumatic chylous effusion; it was usually manifested as dyspnea or abdominal distention. Patients with nontraumatic chylous effusion usually run a chronic course. The characteristics of chylous effusion were analyzed. Lymphangiography and lymphoscintigraphy with 99m TC-labeled dextran play important roles in diagnosis and treatment. It has been suggested that the changes in T-cell immunocompetence is important in determining whether the treatment should be conservative or operative. If chylous effusion is due to tuberculosis, antituberculosis treatment should be instituted. PMID- 1914672 TI - [Clinical significance of determination of urinary albumin, beta 2 microglobulin and Tamm-Horsfall protein in diabetics]. AB - Twenty-four hour urinary albumin (Alb) beta 2 microglobulin (beta 2m) and Tamm Horsfall protein (THP) were measured by radioimmunoassay in 69 diabetics and 23 normal controls. The excretion of urinary Alb, beta 2m and THP in the patients with diabetic nephropathy was found to be different from that of normal controls. The abnormality of excretion of Alb, beta 2m and THP is particularly evident in the patients with clinical diabetic nephropathy. These results indicate that the renal lesions of diabetes mellitus exist not only in the glomeruli but also in the proximal and/or distal tubules. There was a significantly positive correlation between THP excretion and creatinine clearance (less than 127 ml/min/1.73m2). The findings suggest that the excretion of urinary THP is a valuable index for evaluating the damages of nephrons. It is believed that determination of urinary Alb, beta 2m and THP in diabetics is beneficial to early detection of the sites and degree of the renal lesions. PMID- 1914674 TI - [Specific serum IgG antibodies against phthalic anhydride in occupationally exposed workers]. AB - Specific IgG antibodies against phthalic anhydride (PA) was determined in fifty heavily exposed workers, thirty non-exposed subjects and twelve patients with asthma as control groups. ELISA method was used by phthalic anhydride conjugated to human serum albumin antigen. The data demonstrated that specific IgG level was significantly increased only in heavily exposed workers. The average OD value was 0.6 +/- 0.47 (positive rate 78%), but 0.04 +/- 0.03 and 0.05 +/- 0.03 respectively in the two control groups. There was no association between the antibody level and clinical symptoms or the duration of exposure. The meaning of such increase requires further study. We believe, however, that in vitro specific IgG assay can be used as an indication of exposure to PA, or for etiological diagnosis of asthmatic patient and as a means to differential diagnosis. PMID- 1914673 TI - [Amyotrophic lateral sclerosis: an analysis of 167 cases]. AB - 167 cases of amyotrophic lateral sclerosis treated in Peking Union Medical College Hospital were analyzed. There was a significant difference between some of the clinical features of amyotrophic lateral sclerosis in China and western countries. The age of onset in China was 10 to 20 years earlier than and the male to female ratio (4.6:1) was 2 times higher than those in the west. Average age of death was 47 years, being earlier than that in the west. Some specific clinical features for early clinical diagnosis were also discussed. PMID- 1914675 TI - [Gas chromatographic analysis of aldicarb and its metabolites in urine]. AB - A method is described for the analysis of aldicarb and its metabolites in urine by GC/FPD. The sample was concentrated with activated charcoal-Florisil column chromatography, eluted by dichloromethane-acetone (1:1v/v). The aldicarb, aldicarb sulfoxide in the eluted solution were oxidized by oxidizing reagent into aldicarb sulfone. The concentration of aldicarb sulfone was analyzed by GC/FPD. The detection limit of 0.0024 mg/L and coefficient of variation of 2.4%-7.4% were achieved. Mean recovery rates were 90.9%, 86.6%, 92.6% for aldicarb, aldicarb sulfoxide and aldicarb sulfone, respectively. PMID- 1914676 TI - [Persistent ethanol drinking increases liver injury induced by trinitrotoluene exposure: an in-plant case-control study]. AB - On the basis of a general survey conducted in a munitions plant, a case-control study was made on the various risk factors of liver damage induced by trinitrotoluene (TNT) exposure in the plant. The result of analysis showed that two factors the amount of ethanol drunk on each occasion and the frequency of drinking every week had a dose response relationship with their OR of occupational TNT Liver damage, but there was no connection between smoking and occupational TNT liver damage and no interaction between drinking and smoking on occupational TNT liver damage. The above results have revealed that exposure to TNT and with a long history of heavy drinking, have a greater risk of suffering from chronic liver impairment than non-drinking TNT exposure workers. PMID- 1914677 TI - [Environmental and occupational exposure to benzene by investigation of expiratory benzene]. AB - In this paper, expiratory benzene due to environmental and occupational benzene exposure during the work-shift and the morning after was studied by the analysing benzene concentrations in environmental air, in breathing air and in urinary phenol concentration. The results showed that the concentrations of expiratory benzene and urinary phenol correlated significantly with exposure to benzene. It is suggested that the expiratory benzene is a good indicator in biomonitoring of workers exposed to benzene. PMID- 1914678 TI - [The study of standard of classroom temperature for middle and primary schools in freezing and cold regions in winter]. AB - In order to study the standard of appropriate temperature for classroom in freezing and cold regions, field and laboratory research were conducted. The results indicated: the appropriate temperature for classroom was 16-18 degrees C or 15-20 degrees C, according to the children's sense of cold and hot at different classroom temperature. The most appropriate classroom temperature was 18-20 degrees C, according to the changes of certain physiological indexes of children. 16-18 degrees C is recommended to be the standard of temperature for the middle and primary school classrooms in the cold regions in China. PMID- 1914679 TI - [Renal function of cations excretion in children predisposed to essential hypertension]. AB - We studied the renal function of cations excretion in 86 normal children, aged 4 6 years old. 24-hour urinary excretion of sodium, potassium, calcium, magnesium, copper and zinc were measured before and after acute oral salt loading. The result showed that urinary sodium levels were significantly lower (101.88 mmol/24 h, 126.58 mmol/24 h, respectively, P less than 0.01) in children with family history of essential hypertension than in those without family history after salt loading. This suggests that the children with family history may have hereditary functional defect in the excretion of sodium before developing hypertension. We also found the renal excretions of potassium, calcium and zinc showed difference between children with and without family history of essential hypertension. PMID- 1914680 TI - [Multivariate analysis on factors associated with preterm delivery]. AB - In order to estimate the occurrence of Preterm Delivery (PD) and factors associated with PD, 1141 perinatal cases at first affiliated hospital were collected by the method of systematic random sampling. The occurrence rate of PD was 6.0%. Multivariate analysis revealed that the history of premature birth, twin pregnancy, polyhydramnios, placenta praevia, premature rupture of fetal membranes and Bart's fetal hydrops were the main risk factors with statistical significance. Path analysis showed that the history of premature birth had indirect positive effect (elevating risk of PD) on PD through premature rupture of the fetal membranes and Bart's fetal hydrops. Similarly, twin pregnancy had indirect positive effect through premature rupture of the fetal membranes and polyhydramnios. It is suggested that proper health care of the pregnant mother attending to the risk factors should be emphasized to prevent the occurrence of PD. PMID- 1914681 TI - [A study of potential risk of HBsAg negative with RPHA]. AB - An experimental study of potential risk of hepatitis B virus infection was carried out on 1,074 donors who were HBsAg negative by RPHA. Those so-called "qualified donors" were reexamined by ELISA and SPRIA for HBsAg, HBeAg, anti-HBc and anti-HBc-IgM, and 89 of them examined for HBV-DNA by spot hybridization. The results showed that their positive rates of HBsAg, anti-HBc-IgM, HBeAg and HBV DNA were 5.96%, 3.35%, 2.14% and 65.17% respectively, with a total positive rate of 9.68%. The present so-called "qualified donors" are undoubtedly playing the role of source of infection to those who need blood transfusion. PMID- 1914682 TI - [Preliminary evaluation of inoculation of hepatitis B vaccine in normal adult subjects]. AB - A total of 107 subjects in population without HBsAg, anti-HBs and anti-HBc were inoculated with hepatitis B vaccine in month 0, 1, 6, respectively and followed up for three years. Seven months after the administration of first dose of vaccine response rate of anti-HBs was 94.4%, of which 68.2% had a S/N ratio greater than 10. Three years later the response rate of anti-HBs dropped to 75.7% and the rate of S/N ratio 10 fell to 46.7%, 20 subjects turned negative for anti HBs and one turned positive for HBsAg. During the same period, of 124 adults who were hepatitis B virus markers negative and were not inoculated, 14 became HBsAg positive (ALT increased in 3 of them) and 3 turned anti-HBs positive. PMID- 1914683 TI - [Dental anxiety among college students]. AB - In an epidemiological survey comprising 920 college students in 1988, dental anxiety was measured among 525 students, using Corah's questionnaire (CDAS). The data were analyzed with the view to evaluate the level of dental anxiety and analyse the cause. The results indicated that the level of dental anxiety in Chinese college students was significantly higher than that in foreign college students, women student's average score is significantly higher than men's (P less than 0.001). The immediate antecedent of painful dental experience, the influence of dental environment, the indirect experiences gained from the attitude of family or peer group, and the lack of knowledge of oral health were multifactorial risk factors of dental anxiety. PMID- 1914684 TI - [Study on environmental characteristics of coal smoke fluorosis areas]. AB - Typical samples of coal, the components and contents of coal smoke as well as the concentration of fluoride, SO2, IP, CO in indoor and outdoor air in fluorosis areas of the Three Gorges region were studied with the advanced methods of analysis in the past three years. Problems, such as the fluoride level of other polluted environmental samples, the distribution of different size particles in air, the total amount of inhabitants' fluoride intake and their intake pathways in the above mentioned areas were also studied in detail. A fundamental understanding of the environmental characteristics of these areas has thus been obtained. PMID- 1914685 TI - [An investigation of endemic fluorine poisoning caused by food contaminated by smoke containing fluorine]. AB - This paper reports an investigation of two endemic fluorine poisoning areas, where living conditions are special and life habits backward. It was found that fluorosis was also caused by burning coal in a primitive way, even though the average fluorine content of the burning was as low as 61.80 mg/kg. PMID- 1914686 TI - [Study on factors affecting aluminium leaching from aluminium-utensils]. AB - Temperature, pH, oxidative substances and other constituents in foods were studied on their effects on aluminium leaching from aluminium-utensils, using ICPAES method for determining the aluminium contents. The influence of heating on accelerating aluminium leaching was stressed and the effect of F- on aluminium leaching was confirmed. Fe3+ and NaCl were suggested for the first time as being able to promote aluminium leaching. The mechanism and practical significance of these effects are discussed. PMID- 1914687 TI - [Serum levels of 25-hydroxyvitamin D in normal Beijing subjects]. AB - This report describes the changes of serum Ca, P, ALP and 25-OH D3 (using protein binding assay) with age in 592 normal Beijing subjects, aged 0-87 years old. The results were: (1) There was highly negative correlation between age and 25-OH D3 (r = -0.380, P less than 0.01), especially after 41 years old, less between age and ALP and least with P and Ca. (2) There was a significant sex difference of 25 OH D3 and ALP (P less than 0.05). Their serum levels were higher in the male than in the female, indicating that the female is easier to suffer from metabolic bone disease than the male after 41 years of age. (3) There was a distinct seasonal variation in serum 25-OH D3 levels, which were lower in winter and Spring than in Summer and Autumn (P less than 0.001), indicating that there is a greater possibility of Vitamin D deficiency in Winter and Spring. PMID- 1914688 TI - [Day care surgery of inguinal hernia and hydrocele of children]. AB - From March 1983 to December 1989, day care operations were done for 12099 children (inguinal hernia 10913, hydrocele 1186) aging from 6 months to 13 years (75.9% of the children were under three). The postoperative complication rate was 0.84% and 15 children (0.12%) required hospitalization. The procedures and indications of the two operations and measures to prevent postoperative complications are discussed. We consider that day care surgery is safe and effective in minimizing the psychological burden of hospitalization, reducing hospital costs and decreasing the risk of cross-infection. PMID- 1914689 TI - [Endoscopic retrograde cholangiopancreatography in children]. AB - Endoscopic retrograde cholangiopancreatography (ERCP) was performed less in children than in adults. Twenty-seven children, aged from 56 days to 14 years (average 6 years), received ERCP from August 1989 to December 1990. The cannulation into the papilla of Vater was successful in 24 children (88.9%) and their pancreaticobiliary ductal system was visualized clearly. Congenital biliary dilatation (CBD) was diagnosed in 16 patients and other biliary disorders in 8 patients. The APBD was confirmed in almost all CBD patients, showing a close etiological relation. It was concluded that ERCP is helpful to diagnose and differentiate pediatric biliary diseases and to study the etiology and pathophysiology of CBD. PMID- 1914690 TI - [Spur valve jejunal interposition in choledochus cystectomy]. AB - During 1983-1990, 113 patients with congenital choledochus cysts were operated upon with the procedure called the spur valve jejunal interposition following total cystectomy, and satisfactory results were recorded in two years follow-up. However, early complications happened in 26.5% patients e.g. postoperative bile leakage, blood vomiting, small intestinal intussusception, adhesive intestinal obstruction, chyliform ascites, and disruption of wound. Six months-2 years after operation, reflux into bile duct and rapid emptying were observed in some cases in barium examination, and abdominal pain was found in 10% of the patients. The latter was probably due to bile gastritis, which never occurred in conventional Roux-y. An experimental study showed two types of reflux into artificial bile duct. Reflux due to intestinal distention should be checked by an one way valve, while reflux due to normal peristalsis of intestine would be naturally prevented by the intrabiliary pressure formed by the normal bile flow in a narrow bile duct. A spur valve serves an one way stopper and makes the artificial bile duct narrow. In conventional Roux-y, the biliary drainage limb (the artificial bile duct) is the natural path from the distal jejunum while the duodenal drainage limb is just a side-path of the G. I. tract. A wedge anastomosis designed for Roux-Y may convert the natural and side path relationship of the two drainage limbs and would be benefit to avoid reflux into the artificial bile duct. PMID- 1914691 TI - [Surgical treatment of complex congenital heart defect in children and infants]. AB - From January 1982 to June 1990, 2730 patients with congenital heart defects (CHDs) were treated. 537 patients had complex lesions. Fifty of them died, a mortality rate of 9.31%. The operative age ranged from 2 days to 11 years (mean 3.16 +/- 1.68 years), and weight from 2.2 kg to 29 kg (mean 12.2 +/- 3.99 kg). Repair with deep hypothermia plus circulatory arrest was performed in 58 patients, moderate hypothermia plus cardio pulmonary bypass in 459, and normal thermic bypass in 8. The clinical experience concludes that an accurate diagnosis should be made promptly in neonates with complex CHDs. In the cyanotic neonates, surgical results can be improved by use of PGE1 and balloon atrial septostomy. For congestive CHDs, operation must be performed earlier to prevent pulmonary hypertension. PMID- 1914692 TI - [Application of Ilizarov's external fixator on the basis of biology]. AB - Ilizarov's biology includes that, in the presence of tension and stress, both regeneration of bone and soft tissues with cellular proliferation and their biological synthesis become vigorous. The Ilizarov's external fixator has five functions namely: compression, distraction, de-angulation, derotation and translocation. The principles of this procedure include: corticotomy instead of conventional osteotomy, placement of 4-5 sets of 1.5 mm wires transfixed in the bones at different levels under tension of 70-110 kg on the circular rings without acute diastasis until the 5 th to 7th day, and then, callotasis-callus distraction. The quality and quantity of the regenerated bone within the widening distraction gap are closely related to the maximum preservation of bone marrow and periosseous blood supply, and a distraction of 1 mm per day and preferably done by 4 times 0.25 mm each time should be emphasized. Experiences in 17 cases of pseudarthrosis and unequal length of leg treated with Ilizarov's technique are presented. PMID- 1914693 TI - [Subchondral bone tissues in osteoarthritis of knee joint: a tetracycline labelling study]. AB - The patients with late osteoarthritis of the knee joint were given oral tetracycline to label the newly formed bone tissues before they were subjected to high tibial osteotomies or knee replacements. During the operation, the sclerotic subchondral bone tissue of the tibia and/or femur were procured. The bone specimens were processed into undecalcified sections and studied under fluorescence microscope. Apart from the autofluorescence of the trabeculae, strips of golden green labelled fluorescence of high intensity were noted along their peripheries, indicating that there were formatting and deposition of new bone along the periphery of the trabeculae. These new bone tissues were produced by the osteoblasts abutting the trabecular periphery. In the fatty tissues of the marrow interstices between the trabeculae, scattered dots and small flakes of golden green labelled fluorescence emerged at first. Then the labelled fluorescent dots and flakes agglomerated into large pieces of more intense fluorescence with concomitant decrease in fatty tissues. Eventually, these large pieces of labelled fluorescence fused with those of the trabeculae and there was a further decrease in fatty tissues. These findings suggested that the formation and deposition of new bone tissues in the marrow interstices proceeded according to above three stages. The new bone tissues were produced by marrow stromal cells. The two kinds of new bone tissues increased the bone mass and rendered sclerotic changes in upper end of the tibia and lower end of the femur in osteoarthritis of knee joint. PMID- 1914694 TI - [Diagnostic value of magnetic resonance imaging for chronic injury of spine and spinal cord]. AB - From March 1989 to July 1990, Magnetic resonance imaging (MRI) examination was conducted in 60 patients with chronic injuries of the spine and the spinal cord, of whom 32 patients received exploration and decompression operation. Based on the results of MRI, clinical neurological examinations, biological electrical examinations were compared treatment. MRI proved to show the minute changes of the spine, the definite location of spinal compression, the narrowing of spinal canal and the actual cause of compression objects. Thus, it is helpful in selecting treatment and in predicting prognosis. PMID- 1914695 TI - [Bone matrix gelatin. Clinical application in 38 cases]. AB - Bone matrix gelatin (BMG) was prepared and used clinically as graft-stuff in 38 patients. It was used to fill the bone defects resulted from excision of benign bone tumors (22 patients) and debridement of chronic osteomyelitis (3), to treat delayed union of fractures (5), and to make posterior spinal fusion (8). Fourty five days after operation, speckles or flakes of dense shadow appeared in the film at the original defects and fields. In 2 to 6 months, bony union took place in 36 patients (95%). Failure was noted in 2 patients with chronic osteomyelitis. Because of its excellent osteo-inductive property and nonantigenic treat, BMG has been proved to be an ideal substitute for bone graft. It is easy to prepare, safe for storage at room temperature and sound for transportation. PMID- 1914696 TI - [Deaths due to acute pancreatitis]. AB - In 908 patients with acute pancreatitis (AP), 77 belonged to necrotic AP, 34 patients died (14 sudden deaths). Diagnosis was verified by autopsy in 24 cases, by surgical exploration in 8, and by other means in 2. It was found that owing to the lack of information from autopsy, more AP deaths were neglected. In some AP cases, hemorrhage and necrosis in the pancreas happened in several hours. The severity of the pathologic changes in the pancreas (hemorrhage, necrosis) was not proportional to the mortality rate of AP especially in those sudden deaths, a fact implicating a systemic lethal factor released at the early stage of AP. we used systemic support of AP patients at the early stage and explored the patients only when complications ensued. Neither Ranson nor Imire risk factors was helpful in predicting sudden deaths of AP cases. PMID- 1914697 TI - [Percutaneous needle aspiration biopsy of mediastinal lesions]. AB - Percutaneous needle aspiration biopsy of mediastinal lesions was done in 49 patients. A high diagnostic value was obtained from lung (80%) and thymoma (70%) in mediastinal metastasis. The diagnostic rate for mediastinal malignant lymphoma, benign mediastinal cysts, and teratoma was 66.7%, 50% and 50% respectively. Pathological diagnosis of neurogenic tumors showed a positive rate of 33.3%. The procedure therefore, should be used selectively. PMID- 1914698 TI - [Extended parietal cell vagotomy in the treatment of perforation, hemorrhage, and stenosis due to duodenal ulcer]. AB - Ninety-five patients with perforation, haemorrhage, and stenosis due to duodenal ulcer were treated by extended parietal cell vagotomy (EP-CV). Eighty-eight (92%) (acute perforation 60 patients, haemorrhage 8 and stenosis 20) of them were followed up for 3.5 to 10 years (average 6 years). There was no operative death except for 2 documented recurrent ulcers (2.3%) and 1 recurrent stenosis. Of the 88 patients, 67 (76.3%) belonged to class I, 13 (14.7%) class II, 4 (4.5%) class III, and 4 (4.5%) class IV according to visick system. We believe that EPCV is effective in the treatment of perforation, haemorrhage, and stenosis of duodenal ulcer. PMID- 1914699 TI - [The liver in the pathogenesis of multiple organ failure]. AB - Our previous experimental studies showed that the liver is firstly and most severely involved in metabolic damage among various organs after hypoperfusion and sepsis. Changes of metabolites in liver and other organs as well as the function of circulating leukocytes were measured in three rat models with liver ischemia, or systemic hypoperfusion and sepsis. Partial liver ischemia 120 minutes after reperfusion not only resulted in significant decline of ATP and GSH levels in ischemic liver lobes but also in metabolic disorders in non-ischemic liver lobes, kidney, and small intestine. The amount of circulating white blood cells and zymosan stimulated chemoluminescence was increased. The findings showed that ischemic injury in partial liver may accelerate the whole liver damage and aggravate the metabolic disorders in other organs as well as the deterioration of homeostasis. Changes of liver sulfhydryl group levels and related metabolism were estimated. Significant decrease in liver sulfhydryl group levels during hypoperfusion and sepsis may contribute to various cellular metabolic disorders and destruction in early liver damage. PMID- 1914700 TI - [The effects of verapamil on calcium and magnesium concentrations during intestinal shock in rats]. AB - In rats with shock induced by superior mesenteric artery occlusion (SMAO), the concentration of calcium in liver cell mitochondria increased and that of magnesium decreased. In the same period, the calcium concentration in the homogenate of liver, lung, and kidney also decreased. 5mg/kg verapamil, which was given subcutaneously one hour before SMAO, could reversed the above calcium concentrations that the calcium concentration in liver cell mitochondria decreased and that in the homogenate of liver, lung, and kidney increased. We described the mechanism and clinical implications of the changes of calcium and magnesium concentrations during shock of SMAO, and the possibility of treatment with verapamil. PMID- 1914701 TI - [Correlation between retinal nerve fiber layer defect, neuroretinal rim area and visual impairment in primary open angle glaucoma]. AB - 120 eyes of normal subjects, 150 eyes of ocular hypertension, and 132 eyes of primary open angle glaucoma (POAG) were examined the retinal nerve fiber layer (RNFL), neuroretinal rim area (NRA), visual field, dark adaptation and pattern reversal visual evoked potential (PVEP), revealing that RNFL defect and NRA correlated with visual field defect, threshold of dark adaptation and latency of PVEP. RNFL examination using red free photographic technique yielded 96% sensitivity in glaucoma detection and 95% specificity in identifying normal eyes. Modified semiquantitative criterion for assessing RNFL defect had a good reproducibility. The mean NRA in normal eyes was 2.22 +/- 0.35 mm2. Therefore, 95% of the normal subjects had rim areas greater than 1.64 mm2; 82% of patients with POAG had NRA less than 1.64 mm2. 20.1% of the eyes of ocular hypertension had RNFL defect and 37.6% had NRA below the 95% lower point, suggesting that some patients with increased intraocular pressure could have structural abnormalities. The authors proposed that ocular hypertension without visual field defect but with significant RNFL defect and/or NRA decrease should be regarded as in a preliminary stage of POAG. PMID- 1914702 TI - [The effect of topical metoprolol on intraocular pressure]. AB - A single dose of topical 2% metoprolol, a new beta adrenergic antagonist, induced a significant IOP reduction in 20 normal volunteers (40 eyes) and 20 patients (40 eyes) with primary open angle glaucoma. The IOP of the latter 40 eyes remained significantly below the pretreatment levels during 6 months of continued application of the drug b.i.d. No changes were noted in pupil size, blood pressure, or heart rate, indicating that metoprolol is an effective ocular hypotensive. PMID- 1914703 TI - [The ocular hypotensive effect and side reactions of domestic clonidine eyedrops]. AB - The single dose test was performed on 100 various cases of glaucoma, with prolonged use t.i.d. for 1 month in 30 cases, for 3 months in 50 cases, for 6 months in 30 cases, and for 1 year in 20 cases. The IOP was lowered by an average 20%, the effect being similar to that of timolol. Clonidine lowered the blood pressure by less than 10%, and the papillary perfusion index was increased rather than decreased. The discomforts, such as thirst, somnolence and dizziness were tolerable and diminished with continued use. The author recommends its wide application in treatment of glaucoma. PMID- 1914704 TI - [Cerebral and carotid arterial radiograms in low tension glaucoma]. AB - Cerebral and carotid arterial radiograms were performed for 22 healthy volunteers, 8 patients with primary open angle glaucoma(POAG), and 10 patients with low tension glaucoma (LTG). Analysis of the Time-Radioactivity Curves suggested that insufficient perfusion of the carotid artery, especially the internal carotid artery, might play an important role in the optic nerve damage of some cases of LTG. PMID- 1914705 TI - [Histo- and ultrahisto-pathology of the anterior chamber angle in congenital glaucoma]. AB - 92 trabeculectomy specimens of congenital glaucoma, aged 35 days to 46 years, were studied by light and transmission electron microscopy, with findings of narrowed anterior chamber angle, thickened ciliary muscle displaced forward, and crooked or thickened trabeculae, many disintegrated with hyaloid degeneration. The cribriform meshwork appeared dense, with deposition of fibrillae and collagen or basement membrane-like material; Schlemm's canal was absent in 3 specimens; in some the lumen was narrowed or locally obliterated; and Descemet membrane-like substance covered the trabecular meshwork. The types of pathological changes, their relationship with the symptoms, and the locations of outflow resistance were discussed. PMID- 1914707 TI - [Refractive regression after intraocular lens implantation]. AB - Study of refractive changes after IOL implantation in 147 eyes revealed that astigmatism tended to increase, and the natural regressive course followed a negative exponential function, with the steep phase within 3 weeks for spherical, and 5 weeks for cylindrical errors. One (1) week after surgery, the axis of astigmatism was predominantly with the rule, and 2 months after operation, patients with preoperative WRA changed into various astigmatic axial directions, while 76.4% of the patients with preoperative ARA reverted to ARA. Those eyes in which the astigmatic axis was not horizontal 1 week after operation ended with stronger astigmatism in 2 months. PMID- 1914706 TI - [The exfoliation syndrome: report of 9 eyes in 7 patients]. AB - The clinical and histological manifestations in 7 patients (9 eyes) with the exfoliation syndrome were discussed, including some symptoms and signs that had not been reported before, e.g. the changes in form and locality of the exfoliation material. The author is of the opinion that glaucoma may be related to the exfoliation syndrome, while cataract is not. Therefore, early diagnosis of the syndrome is significant for the prevention and treatment of glaucoma. PMID- 1914708 TI - [Cystoid macular edema after rhegmatogenous retinal detachment surgery]. AB - 51 eyes of rhegmatogenous retinal detachment successfully reattached were prospectively studied with regard to the incidence of cystoid macular edema (CME). 14 eyes had CME 6 weeks after surgery, representing an incidence of 27.5%. No correlation was observed between CME and foveal involvement of the detachment, age of the patient, or the amount of subretinal fluid drained. CME is an important cause of postoperative visual impairment, and diagnosis is confirmed by fluorescein angiography. The angiographic features and classification of CME are described. PMID- 1914709 TI - [Management of cilio-choroidal detachment associated with rhegmatogenic retinal detachment]. AB - 51 cases (17%) of cilio-choroidal detachment were associated with rhegmatogenic retinal detachment in a series of 305 cases of the latter. The prominent feature in these cases was extraordinary hypotony, which was an important factor in pathogenesis of the transudative ciliochoroidal detachment. Among the 46 cases that underwent surgical operation, the rate of successful retinal reattachment was 70% (32/46) after a follow-up of 26 months. The good results were believed to have been due to early diagnosis, high dosage topical and systemic steroid therapy, intensive mydriasis, and performance of the retinal surgery as soon as the severe uveitis became alleviated. PMID- 1914710 TI - [Immunological study of endogenous uveitis. I. Dynamic study of autoimmunoreaction]. AB - The autoimmunoreaction was determined with pig eye antigen and bovine retinal soluble antigen (S-Ag) in 77 patients with endogenous uveitis (EU) and 100 healthy individuals. The results showed that lymphocytes of 6 (35.3%) of 17 patients with EU reacted to bovine S-Ag, while those of all 10 healthy subjects were negative. The positivity and titers of serum autoantibodies in the patients with EU were significantly higher than in the healthy subjects and was also related to the activity of EU. These data suggested that the S-Ag sensitized lymphocytes played an important role in the pathogenesis of pan-uveitis, and the serum autoantibodies were significant in the aggravation of EU. PMID- 1914711 TI - [An experimental study on the primary cell culture of human trigeminal ganglion]. AB - A primary cell culture of human fetal trigeminal ganglion in vitro was first established. The growth features and morphology of the three types of cells in the trigeminal ganglion were described. The neurons in the culture were identified with the immunoperoxidase technique. A new model for studying the latent infection of herpes simplex virus type 1 in human is provided. PMID- 1914712 TI - [The volumes of the orbit and the eyeball in human embryos]. AB - The orbital and eyeball volumes in 176 and 126 human embryos were measured respectively. The results showed that the orbit and the eyeball increased in volume with the age of the fetuses, while the corresponding ratios between the two differed insignificantly, indicating that the orbit and the eyeball developed parallelly during gestation. PMID- 1914713 TI - [An experimental study of the effect of severed ocular recti on anterior segment circulation]. AB - The effect of recti tenotomy on the blood flow in iris-ciliary body was studied in 30 anaesthetized dogs with 51Cr labelled RBC of the frog as biological microspheres. The quantitative determinations showed that the blood flow in eyes with 2, 3, and 4 recti detached were 4.47%, 20.80%, and 26.15% less respectively than that of the sham-operation controls, indicating that tenotomy of more than 3 recti compromised the anterior segment circulation seriously. The development of ischemia depended on the number of vertical recti severed when the regional circulation was in a critical situation with the detachment of 2 recti. PMID- 1914714 TI - [Q-switched Nd:YAG laser surgery on vitreous traction bands]. AB - The Q-switched Nd: YAG laser was used to cut vitreous traction bands in 20 eyes with an effective rate of 85%. The pulse energy ranged from 2.8-8.7mJ, and the total energy required was 196 +/- 155.3mJ. The distance of the laser beam focus to retinal surface was 3.7 +/- 2mm. Nd: YAG vitreolysis is an effective means in releasing traction bands and membranes in the posterior segment of the eye. Adaptation of a proper contact lens and optimal strength of energy with accurate focussing are conducive to increased efficacy and avoidance of retinal injury. PMID- 1914715 TI - Make a dent. PMID- 1914716 TI - Colectomy for constipation: physiologic investigation is the key to success. AB - The results of total abdominal colectomy (TAC) with ileorectal anastomosis as a treatment for colonic inertia (CI) were prospectively assessed. One hundred sixty three patients were evaluated for chronic constipation between July 1988 and November 1990. Patients underwent pancolonic transit times, anorectal manometry, cinedefecography (CD), and electromyography (EMG). CI was defined as diffuse marker delay on transit study without evidence of puborectalis contraction on CD or EMG. Sixteen patients (10 percent; 15 females and 1 male) with a mean age of 45 years (range, 24-75 years) with CI underwent TAC. Preoperative bowel frequency ranged from three per week to one per month; all 16 patients evacuated only with high doses of laxatives, enemas, or both. TAC was performed with no postoperative mortality or major morbidity; three patients were readmitted four times for successful conservative treatment of partial small bowel obstruction. At a mean follow-up of 15 months (range, 2-35 months), these 16 patients reported a mean frequency of spontaneous bowel evacuations of 3.5 per day (range, one to six per day). Patient satisfaction with the operation was "excellent" or "good" in 15 cases (94 percent). Thorough preoperative physiologic evaluation permits the selection of a small group of patients with CI who may benefit tremendously from TAC. PMID- 1914717 TI - Indeterminate colitis predisposes to perineal complications after ileal pouch anal anastomosis. AB - This study retrospectively evaluated 288 patients who had undergone ileal pouch anal anastomosis to determine the incidence of perineal complications and to relate these findings to the pathologic diagnosis, with the goal of specifically clarifying the appropriate surgical management of patients with indeterminate colitis. Of these 288 patients, 235 patients (82 percent) had a diagnosis of chronic ulcerative colitis, 18 patients (6 percent) had indeterminate colitis, 6 patients (2 percent) had Crohn's disease, and 29 patients (10 percent) had familial polyposis. All complications occurred at least 6 months after closure of the stoma and required operative therapy. Of 18 patients with indeterminate colitis, 9 patients experienced complications (50 percent) vs. 8 of 235 patients with chronic ulcerative colitis (3 percent), a highly significant difference (P less 0.001). Furthermore, the risk of eventual ileostomy because of perineal complications was 0.4 percent in patients with chronic ulcerative colitis vs. 28 percent in patients with indeterminate colitis (P less than 0.001). We conclude that a diagnosis of indeterminate colitis predisposes the patient undergoing ileal pouch-anal anastomosis to perineal complications, with a resultant high chance of reservoir loss. Ileal pouch-anal anastomosis should be considered with caution in the patient with a diagnosis of indeterminate colitis. PMID- 1914718 TI - Treatment of diversion colitis by short-chain fatty acids. Prospective and double blind study. AB - Diminished production of short-chain fatty acids (SCFA) by altered flora has been suggested in the pathogenesis of diversion colitis (DC). We evaluated prospectively the effectiveness of SCFA irrigation in 13 patients with excluded colon (eight males, five females; mean age, 48 years). The causes of diversion were inflammatory bowel disease (n = 4), colonic cancer (n = 2), sigmoid diverticulitis with perforation (n = 3), ischiorectal abscess (n = 2), and miscellaneous (n = 2). Patients were given, twice a day for 14 days in a double blind manner, a 60-ml enema containing either SCFA (acetate: 60 mmol/liter; propionate: 30 mmol/liter; and N-butyrate: 40 mmol/liter) (Group 1; n = 7) or isotonic NaCl (Group 2; n = 6). Endoscopy with biopsies was performed before starting the trial (D1) and 14 days later (D14). On D1 all patients had endoscopic and histologic findings suggestive of DC. No endoscopic or histologic changes were observed on D14 in either group. We conclude that endoscopic and histologic lesions of DC were not improved by SCFA irrigation during the 14 days. PMID- 1914719 TI - Surgical management of intestinal radiation injury. AB - The management of 14 cases of radiation injury to the intestinal tract over a 4 year period is evaluated. The longest latent interval between radiation treatment and symptoms was 30 years. Eight patients were treated surgically; six were treated conservatively by laser therapy or application of formalin to the affected mucosa. The indications for surgery were rectovaginal fistula (four), rectal stricture (one), radiation proctitis (eight), and small bowel obstruction (one). Seven patients underwent large bowel resection. These consisted of four anastomoses with coloanal J-reservoirs, two low anterior resections, and one coloanal anastomosis without reservoir. There was no perioperative mortality. Morbidity occurred in one of the eight surgical cases. Radical resection of the radiation-damaged rectum has been shown to be a safe and reliable treatment for rectovaginal fistulas, rectal strictures, and proctitis unresponsive to medical measures. Coloanal J-reservoir is the procedure of choice to avoid urgency and frequency symptoms associated with coloanal sleeve anastomosis. Laser therapy for hemorrhagic proctitis can achieve an important place in the management of this problem without recourse to surgery. PMID- 1914721 TI - Transanal excision of large, rectal villous adenomas. AB - The purpose of this study is to demonstrate that a transanal excisional approach can be successfully used in most cases of large, benign, rectal villous adenomas with acceptable rates of recurrence and complications in comparison with historic controls. A retrospective review of all cases of benign, large, rectal villous adenomas at this institution from 1975 to 1985 was performed. A total of 122 patients had large, benign, rectal villous adenomas excised. All except five were treated by transanal excision. Thirty-eight percent of lesions were more proximal than 8 cm from the anal verge. The average follow-up was 55 months. Twenty-seven percent of patients were treated for residual disease after a known incomplete initial treatment or an adenoma at the same location within 6 months of the original treatment. Thirty percent of patients were treated for recurrent adenoma 6 months after complete initial treatment. Two patients (1.7 percent) with recurrences were found to have invasive carcinoma. Both patients had excisional therapy, and one had additional radiation therapy for these carcinomas. Ten postoperative hemorrhages and two perforations occurred as symptomatic or serious complications. This renders a 10 percent complication rate for the study group, which is lower than reported by others using the Kraske or trans-sphincteric approach to the rectum. Because of the expected higher recurrence rate, regular follow-up is necessary for this type of therapy. In conclusion, this study demonstrated that transanal excision of large, benign, rectal villous adenomas can be a safe and effective method of treatment. PMID- 1914722 TI - Continent colostomy by means of a new one-piece disposable device. Preliminary report. AB - A study was established concerning a continent colostomy system consisting of a new one-piece disposable plug. Twenty patients participated: 13 men and 7 women, who ranged in age from 35 to 87 years. All patients had an end colostomy located on the left lower quadrant. The colostomy age ranged from 2 months to 7 years. Of the 20 participants, 17 found the new procedure to be safer and more comfortable, as well as a considerable improvement for their quality of life. The other three patients found no advantage in its use. In no case was there any perception of local, secondary, or general adverse effects owing to its use. Taking into consideration that the use of this new device does not require any type of special conditioning, we consider that it can contribute to the better quality of life of a colostomy patient, the one best able to evaluate the worthiness of its use. PMID- 1914720 TI - Autotransplantation of the pylorus sphincter at the terminal abdominal colostomy. Experimental study in dogs. AB - A method for constructing a continent colostomy has been tried in dogs. The pylorus sphincter with blood supply by the left gastroepiploic vessels was transposed around or anastomosed to the terminal abdominal colostomy in five dogs. One dog had a colostomy without pylorus transplantation. Evaluation was by clinical (consistency and weight of fecal material and number of defecations per day), radiologic, and manometry studies. There was no difference in the clinical data. In all the dogs, the radiologic study demonstrated emptying of the contrast medium to the peristomal skin. By manometry one high-pressure zone was demonstrated, and, in all dogs with a transposed or anastomosed pyloric segment, the average resting pressure was superior to that of the control dog. However, the transposed pylorus sphincter alone was not sufficient to control continence. PMID- 1914723 TI - Variable gastrointestinal and urologic cancers in a Lynch syndrome II kindred. AB - There are no premonitory physical signs or biomarkers which can identify the genotypic status in Lynch syndrome II. Diagnosis is therefore dependent on the pedigree, with attention to cancer of all anatomic sites, inclusive of those cardinal features of its natural history. The tumor spectrum in Lynch syndrome II has continued to expand commensurately with increasing interest in this disorder. We report a family showing the constant cancer features of this syndrome but, in addition, occurrences of carcinoma of the bile duct, urologic system, and extremely early-onset carcinoma of the pancreas, in patients in the direct genetic lineage who were considered to be candidates for having inherited the deleterious genotype. Diagnosis of Lynch syndrome II is crucial in targeting its surveillance and management. PMID- 1914724 TI - Morbidity and survival of liver resection for colorectal adenocarcinoma. AB - Sixty-two patients underwent hepatic resection for isolated colorectal metastases from 1963 to 1988. The numbers of hepatic resections were: lobectomy, 24 (39 percent); wedge resection, 23 (37 percent); and segmentectomy, 15 (24 percent). The median number of intraoperative blood transfusions was 3.0 units (range, 0-16 units). The median number of days in the hospital following hepatic resection was 13 (range, 4-51 days). There were 19 patients (30 percent), who developed a total of 23 complications. Surgery was required for complications in nine patients. Surgical mortality occurred in 5 of 62 (8 percent) patients. The estimated median survival in 56 patients with one to three metastases was 26 months, with a 28 percent estimated 5-year survival. The median size of the metastases was 4.0 cm (range, 0.7-13 cm). The estimated median survival in 27 patients with metastases less than 4 cm in diameter was 26 months, with a 24 percent estimated 5-year survival. The estimated median overall survival from the time of hepatic resection was 25 months. PMID- 1914725 TI - Anal encirclement with polypropylene mesh for rectal prolapse and incontinence. AB - Seventeen selected patients (mean age, 74 years)--14 with rectal prolapse and 3 with persisting anal incontinence after previous operations--underwent high anal encirclement with polypropylene mesh. There was no operative mortality. Prolapse recurred in 2 (15 percent) of the 13 patients followed up for 6 months or more (mean, 3.5 years). Three (27 percent) of the 11 patients with associated anal incontinence improved functionally, as did the three operated on for persisting incontinence, but only one patient regained normal continence. No breakage, cutting out, or infection related to the mesh was observed. Because of the risk of fecal impaction encountered in three of our patients, the procedure is not advocated for severely constipated patients. Despite the somewhat disappointing results regarding restoration of continence, we find this method useful in patients with rectal prolapse who are unfit for more extensive surgery, in controlling the prolapse to an acceptable degree. PMID- 1914726 TI - Do microscopic abnormalities at resection margins correlate with increased anastomotic recurrence in Crohn's disease? Retrospective analysis of 100 cases. AB - The relationship between histologic changes at resection margins and anastomotic recurrence was evaluated in patients with Crohn's disease. Pathology and medical records from 1960 to 1977 identified 100 patients who met the following criteria: 1) no prior surgery for Crohn's disease, 2) small bowel or small bowel and colonic resection with anastomosis done for Crohn's disease at the Cleveland Clinic, and 3) resection margins available for microscopic analysis. The following histologic features of the margins were evaluated: edema, inflammation, lymphoid aggregates, pyloric metaplasia, fibrosis, cryptitis and crypt abscesses, ulcers, granulomas, villous shortening, mucin depletion, neuronal hyperplasia, and transmural inflammation. Additionally, margins were categorized as histologically normal, showing nonspecific changes, showing changes suggestive of Crohn's disease, and showing changes diagnostic for Crohn's disease. Anastomotic recurrence occurred in 50 patients after an average follow-up period of 11.5 years. Cumulative recurrence-free rates for the four margin categories were not significantly different. Anastomotic recurrence was not associated with any clinical or histologic feature or combination of features. PMID- 1914727 TI - Clinical significance of tumor marker NCC-ST 439 in large bowel cancers. AB - We examined serum NCC-ST 439 for its significance as a tumor marker of large bowel cancer in 121 patients with primary and 36 with recurrent large bowel cancer. Serum NCC-ST 439 was positive in 27.3 percent of the former and 66.7 percent of the latter. It was false-positive in only 5.6 percent of patients with benign diseases. Positive serum NCC-ST 439 correlated with lymph node and liver metastases. The combination assay for NCC-ST 439, CEA, and CA19-9 was positive in 49.6 percent of the patients with primary tumors and 88.9 percent of those with recurrent tumors; in other words, the diagnostic accuracy improved. The results demonstrated that the determination of serum NCC-ST 439 in large bowel cancer might be useful in cancer staging and that NCC-ST 439, if used in combination with CEA, is particularly useful in diagnosing recurrences because of its improved diagnostic accuracy. PMID- 1914728 TI - Surgical therapy for rectovaginal fistulas in ulcerative colitis. AB - During a 9-year period, six women with ulcerative colitis (UC) and rectovaginal fistulas were surgically treated. Three underwent ileoanal pull-through procedures with simultaneous repair of the rectovaginal fistulas. Two patients had Kock pouches, and one had a Brooke ileostomy because extensive destruction of the rectal sphincter prohibited ileoanal procedures. The three patients who had ileoanal procedures all had excellent functional results. There has been no evidence of Crohn's disease or fistula recurrence. We believe that rectovaginal fistulas occur more frequently in UC than is generally accepted, and they can be safely managed with current reconstructive techniques. PMID- 1914729 TI - Fate of the rectum after colectomy and ileostomy for Crohn's colitis. AB - Eighty-four patients had colectomy with ileostomy and oversewing of the rectum for Crohn's colitis. Seventy-two patients were operated on because of intractable disease, colitis in combination with rectal fistulas, and toxic megacolon. The operative mortality was 6 percent, and neither emergency surgery nor treatment with steroids correlated with operative morbidity. After a median 7.7 years of follow-up, 25 ileorectal anastomoses had been undertaken, 16 of which were successful. Twenty-nine protectomies were performed; the resulting 10-year cumulative risk of proctectomy was 50 percent. While the risk of proctectomy was significantly less among patients with a normal rectum at colectomy compared with patients with proctitis, the initial macroscopic degree of proctitis did not correlate with the risk of subsequent proctectomy. The 5-year cumulative ileal resection rate in 29 patients with a rectum in situ but out of circuit was 29 percent. The possibility of a future ileorectal anastomosis should still be considered in patients with proctocolitis. PMID- 1914730 TI - Treatment of outflow tract problems associated with continent ileostomy (Kock pouch). Report of six cases. AB - The Kock pouch procedure has undergone a number of revisions since its conception, including creation of a valve and fascial stabilization. Nevertheless, complications which defeat the goal of continence are not unheard of. Naturally, when such complications arise, the patients are disadvantaged. Major examples include pouchitis and valve leakage. Lesser complications of strictures of the outflow tract, valve prolapse, and tissue loss in the outflow tract are also identified and are surgically remediable. Problems may be successfully addressed by minor corrections under local anesthesia or may mandate more extensive procedures. Examples are provided of such successful cases, which allow patients to derive the benefits of continent ileostomy. PMID- 1914732 TI - Stapled strictureplasty for Crohn's disease. AB - Stapled strictureplasty has been performed on 26 occasions in 22 patients. In contrast with sutured strictureplasty, there were no major postoperative complications. The use of staples provides a method of identifying whether recurrence is at the strictureplasty site. Stapled strictureplasty avoids an enterotomy through recurrent disease and may have advantages over conventional sutured strictureplasty. PMID- 1914731 TI - Enterolith intestinal obstruction owing to acquired and congenital diverticulosis. Report of two cases and review of the literature. AB - Diverticulosis of the small bowel, complicated by enterolith formation with ensuing obturation obstruction, was recently documented in two patients. One patient had an enterolith formed within a Meckel's diverticulum; the other had an enterolith dislodged from an acquired diverticulum. Both patients presented with signs and symptoms of acute small bowel obstruction. Only 20 such cases of bowel obstruction secondary to jejunal enterolithiasis and five cases secondary to Meckel's enterolithiasis have been reported. The mechanism of obstruction may involve local encroachment or enterolith expulsion with distal bowel obstruction, although the latter is much more common. Optimally, enteroliths are broken up and milked into the proximal colon without incising the bowel. Alternatively, the enterolith may be milked proximally to a less edematous portion of bowel and an enterotomy may be performed. At times, the primary diverticulum is resected with the contained enterolith. PMID- 1914733 TI - Anorectal manometry--a call for reason. PMID- 1914734 TI - Fistula-in-ano in Crohn's disease. PMID- 1914736 TI - Sphincter repair without overlapping for fecal incontinence. AB - Forty patients who had sphincter repair by one surgeon over the last 15 years were reviewed. The etiology of sphincter trauma was previous surgery (22), childbirth (14), and accidental trauma (4). Eleven patients had undergone at least one previous attempt at repair. Prior to operation, 12 patients were incontinent for liquid stool and 28 for formed stool. A technique of sphincter repair without overlapping was used. An associated diverting colostomy was carried out on seven patients who had had a previous failed repair. Follow-up was an average of 17 months after operation (range, 2-96 months). After operation, 25 patients were completely continent, 6 had occasional leaks of liquid stool, 4 were continent for solid stool only, and 5 showed no improvement. Neither diverting colostomy nor overlapping sutures appear to be mandatory for a successful repair of the anal sphincter after trauma. PMID- 1914735 TI - Anal sphincter reconstruction: anterior overlapping muscle repair. AB - Anal sphincter reconstruction for anal incontinence was performed in 55 women between 1973 and 1987 at The Jewish Hospital of St. Louis. The mean age was 34 years (range, 22-75 years). Incontinence was due to obstetric injury in 48 patients and to fistulotomy in 7 patients. Patients suffered from complete incontinence (41), incontinence of liquid stool and flatus (11), or incontinence of flatus only (3). All patients underwent an anterior overlapping sphincter muscle reconstruction, and one patient also had a posterior repair. Complete continence was restored in 28 patients, and partial continence was achieved in 24 patients. Only three patients remained totally incontinent. Clinical assessment did not accurately reflect functional outcome after 1 year of follow-up. No factor predicting outcome was found retrospectively. Clinical assessment of a patient's outcome may be inaccurate unless specific questions are asked. The use of a perineal drain reduced infection but did not affect outcome. Previous repair or associated rectovaginal fistula does not affect outcome. Sphincter injury owing to fistula disease may result in poor outcome after repair. PMID- 1914738 TI - Fibrin adhesive in the treatment of perineal fistulas. AB - Fifteen patients who developed a persistent perineal sinus after excision of the rectum and eight patients with a perineal fistula appearing after treatment of perineal abscesses were treated with instillation of fibrin adhesive to close the sinus or fistula. In 12 patients, the sinus tracts or fistulas were completely and permanently closed (52 percent). In five patients (22 percent), the fistulas healed after two or three attempts, while, in six patients (26 percent), the method failed to provide lasting closure. The method seems to be a valuable alternative in the treatment of a persistent, long and narrow perineal sinus or fistula. PMID- 1914737 TI - Predictive value of a negative computed tomographic scan in 100 patients with rectal carcinoma. AB - The predictive value of a negative computed tomographic (CT) scan was assessed in a group of 100 patients with rectal carcinoma by correlating operative findings and pathologic stages in the patients who had no evidence of extrapelvic metastases on a preoperative CT scan. Sixty-four patients (64 percent) had stage T3 or T4 tumors. Ten patients had unsuspected distant metastases for an overall negative predictive value of 90 percent. Seven patients had small liver metastases, and three had periaortic nodal metastases. Six of the patients with liver metastases had them completely resected at the original laparotomy. The predictive value of the CT scan diminished in the patients who were selected to receive full-dose preoperative radiation therapy and had a mean delay of 12 weeks between CT scan and laparotomy. The preoperative carcinoembryonic antigen levels were of no value in predicting the presence of distant metastases. These results show that a negative CT scan will fail to detect 10 percent of patients with small liver metastases or positive periaortic nodes. PMID- 1914739 TI - Delayed ileal pouch-anal anastomosis. Complications and functional results. AB - In patients with chronic ulcerative colitis (CUC), ileal pouch-anal anastomosis (IPAA) can be performed either at the time of colectomy or as a delayed procedure after total abdominal colectomy and ileostomy. There has been debate as to whether delayed IPAA results in superior functional results, since patients are frequently steroid-free and have little evidence of active disease. To assess this, we analyzed 95 patients who had undergone total abdominal colectomy, either with ileostomy and Hartmann's procedure or with ileorectostomy, 2-183 months prior to IPAA. Postoperative complications and functional results were compared with those of 776 CUC patients who underwent IPAA at the time of abdominal colectomy. Indications for prior colectomy included toxic megacolon (40 percent), failed medical therapy (36 percent), other reasons (e.g., iatrogenic perforation, cancer) (6 percent), and reasons unclear (18 percent). Nineteen percent of delayed-IPAA patients were taking steroids at the time of pouch construction. Follow-ups were similar in the two groups. The incidence of septic and obstructive complications after delayed IPAA vs. IPAA at the time of colectomy were 10.5 percent vs. 5.4 percent and 6.5 percent vs. 14.5 percent, respectively. There were no significant differences in postoperative functional results between the two groups. Delayed IPAA confers no advantage over IPAA performed at the time of colectomy in terms of functional outcome. Delayed IPAA was associated with a significantly higher rate of septic complications but a lower incidence of postoperative obstruction. PMID- 1914740 TI - Obstructing colorectal carcinomas. Prospective study. AB - Intestinal obstruction owing to colonic carcinoma is a relatively frequent cause of acute abdominal pain. The aim of this prospective study is to evaluate the prognostic factors that may influence the final outcome of those patients operated upon for an intestinal obstruction (OG) as opposed to those electively operated upon (EG). From September 1984 to March 1988, a total of 188 patients with colorectal cancer have been included in the study. One hundred thirty-five were EG, while 53 (28.1 percent) were OG. The mean ages were similar in both groups. Sex, morbidity, and mortality rates were equally distributed. Curative resection rate was significantly higher in the EG group (P = 0.029). Tumor staging tended to be significantly more advanced in OG patients (chi-square = 9.054; df = 3; P = 0.026). Multivariate analysis (proportional hazards model) showed that the only independent prognostic factor was tumor staging (P = 0.0000). Obstruction itself disappears as a predictive variable when tumor staging is introduced in the model. We conclude that obstructing colon carcinomas tend to be more locally advanced, that probably being the only reason for a worse long-term prognosis. PMID- 1914741 TI - Is colonoscopic screening appropriate in asymptomatic patients with family history of colon cancer? AB - Colonoscopy has been advocated by some investigators as the most appropriate means of screening asymptomatic patients with a positive family history of colorectal cancer. However, results of such screening have been widely disparate. The purpose of this study was to evaluate the yield of colonoscopy in a cohort of completely asymptomatic individuals with one or two first-degree relatives with a history of colorectal cancer and to compare this yield with that of colonoscopy in a group of patients with apparent anal bleeding. Patients with possible genetic disorders, such as familial polyposis, were excluded. A total of 160 asymptomatic patients and a comparison group of 137 patients with nonacute anorectal bleeding underwent colonoscopy. Colonoscopy was completed in 143 of the 160 study patients (89 percent) and in all of the comparison patients and did not result in any complications. Twenty-two adenomas were found in 17 study patients (10.6 percent); 16 of the 22 adenomas were less than 1 cm in size. In the comparison group, eight adenomas were identified (5.8 percent of patients). No cancers were identified. The difference in polyp frequency between groups was not significant. The relatively low yield of colorectal neoplasms discovered at colonoscopy in this study may in part be due to the small sample size or to the strict criteria used to define these asymptomatic patients but does not lend strong support to the notion that colonoscopy is an appropriate first step in screening the asymptomatic patient with one or two first-degree relatives with colon cancer. PMID- 1914742 TI - Behavioral medicine treatment in chronic constipation with paradoxical anal sphincter contraction. AB - Nine women and five children with severe chronic constipation received behavioral medicine therapy. Before treatment, all patients had a paradoxical contraction of the external anal sphincter at defecation attempts as demonstrated with electromyography and/or anorectal manometry. An electromyographic biofeedback device connected to an anal probe was used for the training that was performed on a regular toilet seat during five 1-hour sessions. Thirteen of the patients improved considerably and could learn to defecate spontaneously, and the use of laxatives ceased or diminished. Simultaneously with improvement, the paradoxical anal contraction disappeared. The results remained after 6 months, although two of the patients had received booster sessions of biofeedback training during follow-up. PMID- 1914743 TI - Anterior perineal sinus. AB - Each year we treat several patients with an anterior perineal sinus tract. They do not conform to commonly encountered perineal problems such as pilonidal disease, epidermal cysts, hidradenitis, fistulous abscess, or inflammatory bowel disease. In an effort to improve understanding of the problem and its clinical significance, we reviewed our practice records for the period from 1968 through 1988. Fifty-six patients underwent surgery for an anterior perineal sinus tract. In 31 patients, the clinical and pathologic condition defied classical diagnostic categorization. We have termed these lesions "anterior perineal sinuses." Their clinical characteristics, treatment, and pathologic assessment from the body of this report. Male predominance (87 percent) and midlife presentation (average age, 44 years) characterized this group. Local symptoms were present from several weeks to several years prior to treatment. Local anesthesia (74 percent) and limited surgery (100 percent) resulted in complete healing in all patients (average, 7 weeks). A 15 percent recurrence rate was noted. The pathologic evaluation demonstrated acute and chronic dermal and subcutaneous inflammation. The etiology of this process remains uncertain. Its predominance along the median raphe suggests a congenital midline inclusion disorder. PMID- 1914744 TI - Psoas abscess: difficulties encountered. AB - From 1961 to 1989, 67 patients underwent various surgical procedures for psoas abscess. Retrospective analysis was undertaken in an effort to determine optimal surgical therapy. Forty patients were cured with one operation. Twenty-one patients required two operations, four patients required three operations, and two patients required more than three operations. The reason for failure of treatment was failure to resect the diseased bowel or to drain the psoas abscess adequately. A technique to recognize and treat the abscess definitively will be illustrated. The most common etiologies were Crohn's disease in 49 patients, postoperative sepsis in eight patients, and complications of renal disease in four patients. The length of hospital stay ranged from 5 to 392 days (mean, 26 days). There were two deaths. Failure to recognize and treat psoas abscess results in considerable morbidity. PMID- 1914745 TI - Metachronous colorectal cancer in young patients: expression of the hereditary nonpolyposis colorectal cancer syndrome? AB - The cumulative incidence rate of metachronous colorectal cancer in patients younger than 40 years of age at diagnosis of the primary cancer has been shown to be 30 percent. Metachronous colorectal cancer is predominantly located in the right colon with a decreasing frequency toward the rectum. The risk of developing a metachronous colorectal cancer was found to be 16-29 times increased when compared with the risk of having a primary colorectal cancer. Because of the resemblance between characteristics of metachronous colorectal cancer and the features of hereditary nonpolyposis colorectal cancer (HNPCC), it is proposed that young colorectal cancer patients developing metachronous colorectal cancer could in fact be HNPCC patients. PMID- 1914746 TI - Role of carcinoembryonic antigen and liver function tests in the detection of recurrent colorectal carcinoma. AB - The optimal laboratory evaluation for the early detection of liver metastases from colorectal cancer is controversial. This investigation was undertaken to compare the efficacy of liver function tests (LFTs) with that of carcinoembryonic antigen (CEA) levels for the early detection of liver metastases. Patients who developed liver metastases after potentially curative resections of adenocarcinoma of the colorectum between 1974 and 1988 were reviewed. The following laboratory tests were serially evaluated during the follow-up period: CEA, alkaline phosphatase (AP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and lactic dehydrogenase (LDH). These values were retrospectively assessed from the time of documented liver metastases to identify which lab value(s) were elevated initially. Ninety-two patients were available for study. Average time for the occurrence of liver metastases was 20 months (range, 3-72 months). The incidence of elevation of individual tests at the time of suspicion of liver metastasis was: CEA, 94.6 percent (P less than 0.25, chi-squared); AP, 18.5 percent; SGOT, 12.0 percent; SGPT, 5.4 percent; and LDH, 29.3 percent. When comparing CEA with a battery of LFTs at the time of suspicion of liver metastasis, CEA was elevated with normal LFTs in 64.1 percent (P less than 0.05, chi-squared), the most frequent occurrence. At least one LFT was elevated with a normal CEA in only 2.2 percent; CEA and at least one LFT were increased in 30.4 percent; and both tests were normal in only 3.3 percent. These results indicate that, of the individual laboratory tests performed, CEA elevation heralds liver metastases significantly more frequently. LDH is the liver function test most frequently elevated when liver metastases are first suspected. When CEA is directly compared with a battery of LFTs, CEA is statistically significantly more frequently elevated. In fact, suspicion of liver metastases would have been delayed by the omission of LFTs in only 2.2 percent of patients. Therefore, we conclude that LFTs should be deleted from the follow-up of colorectal cancer patients, decreasing costs without significantly decreasing accuracy. PMID- 1914747 TI - Venous and neural invasion as predictors of recurrence in rectal adenocarcinoma. AB - After radical surgery for rectal adenocarcinoma, the presence of venous and neural invasion of tumor cells was correlated with the pattern of treatment failure, local in the pelvis or distant. Of 128 operation specimens, venous and neural invasion was demonstrated in 22 percent and 32 percent, respectively. A significant decrease of the distant recurrence-free 5-year survival (Kaplan-Meier method) was seen when venous invasion was demonstrated (32.9 percent vs. 84.3 percent; P less than 0.0001), whereas more local failures were registered in patients with neural invasion. The local recurrence-free 5-year survival in patients with neural invasion was 64.3 percent, compared with 81.1 percent when neural invasion was not demonstrated (P = 0.03). Their prognostic value was then studied in a Cox regression model including stage and grade. Neural invasion had the strongest association with local recurrences, whereas venous invasion was found to be the third strongest independent predictor of metastasis, after lymph node status and extent of local tumor infiltration. We conclude that examining for the presence of venous and neural invasion gives reliable prediction of recurrences after radical resection of rectal cancer. Recording of tumor recurrence pattern may lead to a better selection of patients for adjuvant therapy after surgery. PMID- 1914748 TI - Multiple primary colorectal adenocarcinomas: cytometric DNA ploidy patterns and histopathologic features. AB - The nuclear DNA distribution pattern was studied by means of image cytometry in 18 patients with synchronous and 7 patients with metachronous colorectal adenocarcinomas. About 80 percent of a total number of 53 carcinomas were found to consist of neoplastic cells where the nuclear DNA distribution pattern was of the aneuploid type. In 19 of the 25 patients, all carcinomas in the individual colon had identical nuclear DNA distribution patterns. Aneuploid tumors tended to appear more frequently in the sigmoid colon and the rectum than in the right colon. Carcinomas associated with an adenoma were more common in the rectum and in Dukes' A carcinomas. The results of cytometric assessments of the nuclear DNA ploidy pattern of the neoplastic cells in colorectal carcinomas have previously been found to be an independent prognostic variable. From the observations made in the present study, it is concluded that the cytometric DNA ploidy pattern of multiple primary colorectal carcinomas corresponds to that found in single carcinomas. The similarity between the two groups of cancer patients is also supported by conformity between histopathologic features and prognosis. PMID- 1914749 TI - Recovery of anal sphincter function following transabdominal repair of rectal prolapse: cause of improved continence? AB - Twenty-eight patients with complete rectal prolapse underwent anorectal manometry before and 6 months and 1-2 years after abdominal rectopexy and sigmoid resection in a study of the mechanisms responsible for postoperatively improved anal continence. Preoperatively, 22 patients reported defective and control. Seven patients (all with minor incontinence) regained normal control and eight other patients achieved improved continence after surgery. Anal resting, squeeze, and voluntary contraction pressures were significantly lower for defective than for normal control, with a significant rise in these pressures at 6 months after the operation, except for those incontinent patients in whom continence was not improved. No further pressure rise was seen later. Improvement of continence was not accompanied by changes in rectal sensation or reflexive functions of the internal anal sphincter. These results suggest that recovery of the resting and voluntary contraction functions of the sphincter muscles was the cause of continence improvement observed after surgery. Anal manometry was unable to predict outcome of function. Therefore, supplementary procedures for restoration of continence are not advisable, although patients with only minor incontinence are likely to regain full continence after rectopexy alone. PMID- 1914750 TI - Carcinoma of the gallbladder in ulcerative colitis and primary sclerosing cholangitis. Report of two cases. AB - The authors present the cases of two patients with carcinoma of the gallbladder complicating chronic ulcerative colitis. Both patients had concomitant primary sclerosing cholangitis. Twelve such cases of gallbladder carcinoma have been reported in the literature. The presence of primary sclerosing cholangitis in patients with ulcerative colitis is associated with malignancy of the extrahepatic biliary tree. It is suggested that, if colectomy is necessary, the liver should be biopsied and a cholecystectomy performed if the gallbladder is deemed abnormal. PMID- 1914751 TI - Disappearance of hyperplastic polyposis after resection of rectal cancer. Report of two cases. AB - Since 1980, when the first description of hyperplastic polyposis of the colon appeared, 18 cases of hyperplastic polyposis have been reported in the literature. Only two of them bore colonic cancer. Here we add two cases of hyperplastic polyposis accompanying rectal carcinoma following cancer resection, in which residual hyperplastic polyps disappeared after resection. PMID- 1914752 TI - Use of Dexon Mesh for abdominal partitioning above the peritoneal reflection. AB - Dexon Mesh (Davis & Geck, Sugarland, TX) was used to partition the abdomen after incomplete resection of a locally advanced left colon cancer. Following surgery, external beam radiotherapy was delivered to the left flank without the risk of radiation enteritis. The technique of abdominal partitioning using Dexon Mesh is described. PMID- 1914753 TI - The famous gastrocutaneous fistula of Alexis St. Martin. Why didn't it close? Or should we refer to it as a gastric stoma? PMID- 1914754 TI - Effect of elevated intracranial pressure on gastric acid secretion, mucosal blood flow and mucosal injury. AB - Head injury is frequently accompanied by an increase in intracranial pressure and gastric lesion formation. We used a model of controlled intracranial pressure to investigate the effect of elevated intracranial pressure on gastric acid secretion and mucosal blood flow and on the susceptibility of the gastric mucosa to lesion formation. With increasing intracranial pressure, there was a corresponding increase in gastric acid output but no significant change in gastric mucosal blood flow. This imbalance between acid secretion and blood flow could be a factor in the pathogenesis of the gastric lesions seen with head injury. Susceptibility to gastric mucosal injury then was studied in a model that is independent of the acid secretory state--exogenous intragastric HCl plus ethanol. Elevated intracranial pressure did render the gastric mucosa more susceptible to injury in this model, but there was no impairment of the increased gastric mucosal blood flow response to the increased acid back-diffusion. In this situation, factors other than altered overall blood flow appear to be responsible for the increased lesion formation. PMID- 1914755 TI - Inability of cytoprotection to occur during a period of gastric ischemia. AB - Prostaglandin E2 (PGE2), colloidal bismuth subcitrate (CBS), and sucralfate (SUC) are known to protect the gastric mucosa from ethanol injury. The proposed central role for the microcirculation in gastric mucosal defense and as a site for the expression of the protective effects of these agents was investigated in the rat stomach. Animals were pretreated with either PGE2, CBS, or SUC. Control rats were given normal saline. After allowing 15 min for expression of the pretreatment, ethanol was administered as a 10%, 25%, 50%, or 100% solution to groups of rats with normally perfused stomach and to other groups of rats in whom the stomach was made ischemic by cross-clamping the supracoeliac aorta immediately prior to the instillation of ethanol. The extent of gastric mucosal damage was measured using quantitative histological techniques and expressed as a percentage of surface area and volume of mucosa damaged. In the presence of ischemia, the extent of damage by ethanol was markedly increased, with total destruction of the mucosa by the 50% and 100% solutions. With 25% ethanol, the volume of mucosal damage was increased from 0.5% in the normally perfused stomach to 53.5% with ischemia. When 10% ethanol was instilled into the ischemic stomach, only 0.8% of the volume of the mucosa was damaged, which was not different from the volume of mucosa damaged after the ischemic stomach was exposed to normal saline alone (1.0%). Pretreatment with PGE2, CBS, or SUC did not significantly change the extent of damage seen with exposure of the ischemic stomach to 25% or 50% ethanol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914756 TI - Emptying of the gastric substitute, glucagon-like peptide-1 (GLP-1), and reactive hypoglycemia after total gastrectomy. AB - Postprandial glucagon-like peptide-1 (GLP-1), pancreatic glucagon, and insulin were measured in 27 tumor-free patients 43 months (median) after total gastrectomy and in four controls using a 99technetium-labeled 100-g carbohydrate solid test meal. Emptying of the gastric substitute was measured by scintigraphy. Fourteen patients suffered from early dumping symptoms, and five of them also reported symptoms suggestive of reactive hypoglycemia (late dumping). The median emptying half-time (T1/2) of the gastric substitute was 480 sec. Sigstad's dumping score was 8.5 +/- 1.6 (mean +/- SE) in patients with rapid emptying (T1/2 less than 480 sec), and 3.0 +/- 1.5 in patients with slow emptying of the gastric substitute (P = 0.02). The peak postprandial concentration of GLP-1 was 44 +/- 20 pmol/liter in controls, 172 +/- 50 in patients without reactive hypoglycemia, and 502 +/- 116 in patients whose glucose fell below 3.8 mmol/liter during the second postprandial hour. Plasma GLP-1 concentrations peaked at 15 min, and insulin concentrations at 30 min after the end of the meal. A close correlation between integrated GLP-1 responses and integrated insulin responses (r = 0.68) was observed. Multiple regression revealed that three factors were significantly associated with the integrated glucose concentrations during the second hour (60 120 min): Early (first 30 min) integrated GLP-1 (inverse correlation; P = 0.006), age (P = 0.006), and early integrated pancreatic glucagon (P = 0.005). There was a close (inverse) relationship of T1/2 with early integrated GLP-1 and pancreatic glucagon, but not with insulin. Gel filtration of pooled postprandial plasma of gastrectomized individuals revealed that all glucagon-like immunoreactivity eluted at Kd 0.30 (Kd, coefficient of distribution), the elution position of glicentin. Almost all of the GLP-1 like immunoreactivity eluted at Kd 0.60, the elution position of gut GLP-1. The authors contend that GLP-1-induced insulin release and inhibition of pancreatic glucagon both contribute to the reactive hypoglycemia encountered in some patients following gastric surgery. Rapid emptying seems to be one causative factor for the exaggerated GLP-1 release in these subjects. PMID- 1914757 TI - Definition for idiopathic gastric acid hypersecretion. A statistical and functional evaluation. AB - Zollinger-Ellison syndrome and other gastric acid hypersecretory states in which a specific etiology is identified are defined as a basal acid output of greater than 15.0 meq/hr. To determine the level of basal acid output that defines idiopathic gastric hypersecretion, basal acid outputs were investigated in normal subjects and patients with duodenal ulcers, and functional and statistical definitions for idiopathic gastric acid hypersecretion were developed. Sixty-five normal subjects were evaluated to define idiopathic gastric acid hypersecretion on a statistical basis, and 22 patients with refractory duodenal ulcers were evaluated to define idiopathic gastric acid hypersecretion on a functional basis. Mean basal acid output for the 65 normal subjects was 3.0 +/- 2.7 meq/hr. Even though the mean basal acid output for the group of 28 normal male subjects was slightly higher than for the group of 37 normal female subjects, the groups were not significantly different. The 95% confidence interval around the mean basal acid output for all normal subjects was 2.4-3.7 meq/hr, with little difference between the male and female groups. The mean basal acid output plus two standard deviations and the mean basal acid output plus three standard deviations for the 65 normal subjects were 8.4 meq/hr and 11.1 meq/hr, respectively. Of 109 patients with active duodenal ulcers treated for eight weeks with standard doses of antisecretory medication, 22 showed no healing as documented by endoscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914759 TI - Comparative tolerability profile of omeprazole in clinical trials. AB - The tolerability of omeprazole was compared to control agents in 68 clinical studies that enrolled a total of 4846 patients, of whom 3096 received omeprazole. The incidence of adverse experiences was independent of omeprazole dose administered, the age of the patients, and the disease treated (duodenal ulcer or endoscopically verified gastroesophageal reflux disease). The most common clinical adverse experiences were headache, diarrhea, abdominal pain, and nausea. The most common laboratory adverse experiences were elevated aspartate aminotransferase and elevated alanine aminotransferase. Omeprazole was well tolerated, and the incidence of clinical and laboratory adverse experiences was similar in patients receiving omeprazole, placebo, cimetidine, or ranitidine. PMID- 1914758 TI - Very-low dose antacid in treatment of duodenal ulcer. Comparison with cimetidine. AB - Antacid (AA) in a very low dose (88 mmol/day) was compared to the standard 800-mg dose of cimetidine in healing duodenal ulcers. The influence of sex, age, symptom duration at entry, night pain, smoking, coffee consumption, and alcohol on ulcer healing was studied. The antacid was given in two different schedules: group I- 20 ml 1 hr after breakfast and at bedtime; group II--10 ml 1 hr after breakfast and lunch and 20 ml at bedtime. Cimetidine (group III) was given in two divided doses: 400 mg 1 hr after breakfast and 400 mg at bedtime. Endoscopic control was performed after four weeks and, if necessary, after eight weeks of treatment. The healing rate after four weeks of treatment was, respectively, for groups I, II, and III, 45.5%, 55.8%, and 69.4% (group I = group II, and group III different from groups I and II). After eight weeks of treatment the healing rate was 61.5%, 80.8%, and 88.0% for groups I, II, and III, respectively (group II = group III, and group I different from groups II and III). Except for group I, smoking did not influence healing rate. Age, sex, symptoms at entry, night pain, and coffee consumption did not influence the treatment results. The authors concluded that the very low dose of magaldrate (88 mmol/day), when administered in three divided doses (10 ml after breakfast and lunch and 20 ml at bedtime) for eight weeks was as effective as 800 mg of cimetidine (400 mg twice a day) in healing duodenal ulcer. PMID- 1914760 TI - Effect of cimetidine on marathon-associated gastrointestinal symptoms and bleeding. AB - Occult gastrointestinal bleeding occurs in 8-30% of marathon runners. We hypothesized that cimetidine would decrease bleeding by reducing acid-mediated injury and conducted a blinded, placebo-controlled prospective trial to determine the impact of cimetidine on gastrointestinal symptoms and bleeding during a marathon. Thirty participants in the 1989 Marine Corps or New York City marathons completed pre- and postrace: (1) a questionnaire evaluating demographic, medication usage, training history, and gastrointestinal symptoms; (2) three consecutive stool Hemoccult (HO) cards; and (3) a stool Hemoquant (HQ). Fourteen runners (CR) took 800 mg of cimetidine by mouth 2 hr before the start and 16 runners (PR) took placebo. Three subjects were HO+ prerace and were not analyzed. Three subjects failed to take drug as directed and were analyzed as PR. Five of 14 PR and two of 13 CR were HO+ postrace (P greater than 0.05). Prerace HQ values (PR: 1.49 +/- 0.6 and CR: 0.60 +/- 0.1 mg hemoglobin/g stool) were not significantly different from postrace HQ values (PR: 0.73 +/- 0.2 and CR: 0.86 +/ 0.2 mg Hgb/g stool). Despite postrace HO+ conversion, no individual postrace HQ became abnormal. The frequency of gastrointestinal symptoms was similar for CR and PR, as well as HO- and HO+ individuals. Cimetidine did not significantly affect occult gastrointestinal bleeding as measured by HO or HQ results. This suggests that marathon-associated gastrointestinal symptoms and bleeding may be due to lesions other than acid-mediated disease or hemorrhagic gastritis. PMID- 1914762 TI - Reproducibility of endoscopic sphincter of Oddi manometry. AB - Results from endoscopic sphincter of Oddi manometry are being used to support the diagnosis of sphincter dysfunction in patients with unexplained pain after cholecystectomy. However, there are few data on the reproducibility of manometric records or motility diagnosis during a second test. In this study, the reproducibility of manometric records was assessed in 12 patients with pain after cholecystectomy by performing a second study after three months. Manometric tracings were evaluated without access to patients details and scored for sphincter basal pressure, frequency and amplitude of phasic contractions, propagation of phasic contractions, and responses to intravenous injection of cholecystokinin octapeptide (20 ng/kg). At the initial manometric study, four patients were diagnosed as normal, four as stenotic, and four as dyskinetic. Those diagnosed as normal and stenotic at the first study had an identical diagnosis at the second study. However, the diagnosis of dyskinesia was reproduced only in two of the four patients. In the other two patients a diagnosis of "stenosis" and "normal" was made at the second study. Cholecystokinin octapeptide (20 ng/kg intravenous bolus) produced inhibition of phasic contractions in all studies, both initially and at three months. We conclude that endoscopic sphincter of Oddi manometry is reproducible when the initial diagnosis is either normal or stenosis. However, the diagnosis of dyskinesia is poorly reproducible, perhaps due to the episodic nature of this manometric disorder or to progression of sphincter of Oddi dysfunction. PMID- 1914761 TI - A comparison of omeprazole and ranitidine for duodenal ulcer in South African patients. A multiracial study. AB - The study was a multicenter double-blind parallel-group comparison of omeprazole, a proton-pump inhibitor, with the H2-receptor antagonist, ranitidine, in 206 patients with duodenal ulcer. There were 145 men and 62 women of mixed racial origin with an average age of 40 years (range 19-76); 63 of them were white, 7 black, 135 coloured and 1 Asian. Each drug was given for four weeks and ulcer healing rate, symptom relief, and adverse events were recorded and compared between treatment groups. Patients received either 20 mg omeprazole once daily in the morning (N = 104) or ranitidine 300 mg once daily at night (N = 106). Healing rates were significantly higher in the omeprazole group than in the ranitidine group at both two weeks (80% vs 52%, P less than 0.001) and four weeks (95% vs 85%, P less than 0.05), using the "per protocol" approach, and these results were confirmed using the "intention to treat" approach. Omeprazole-treated patients reported significantly less daytime epigastric pain (P = 0.02) and heartburn (P = 0.04) after two weeks than ranitidine-treated patients. By four weeks, there were no significant differences in symptom reporting between groups. Both treatments were well tolerated, and there were no serious adverse events. PMID- 1914763 TI - Endoscopic retrograde sphincterotomy in swine. AB - Endoscopic retrograde sphincterotomy was performed on four sedated pigs, ages 3-4 months, using a standard human duodenoscope and papillotome. Sphincterotomies, 1 cm in length, were well-tolerated, and all animals recovered promptly, spontaneously regained gastrointestinal function, and gained weight. The first three animals were sacrificed after one week, and autopsy revealed no complications. The fourth animal was sacrificed immediately following the procedure, and no evidence of perforation was found. These observations demonstrate that the pig is a valid experimental model for endoscopic sphincterotomy. Its use in training is limited by technical and anatomic differences from humans. Potential uses of this technique in research are discussed. PMID- 1914764 TI - Percutaneous transhepatic manometry of sphincter of Oddi. AB - A nonoperative examination of the function of the sphincter of Oddi, involving percutaneous transhepatic manometry via the percutaneous transhepatic biliary drainage tract, was developed and clinically applied in 23 patients with biliary disease. Long-term recording of sphincter of Oddi motility, which was impossible using conventional intraoperative or endoscopic manometry, was made possible by means of this method and revealed various changes of sphincter of Oddi motility. The mean recording time was 131.33 +/- 9.77 min. The frequency of contractions of the sphincter of Oddi in basal fasting conditions varied from 0 to 13/min and high-frequency contractions (frequency 9.49 +/- 0.35/min, duration 5.77 +/- 0.54 min) were observed in 12 patients on a total of 19 occasions. In five patients, high-frequency contractions were observed twice during one session of continuous recording and the interval between burst contractions was 85.4 +/- 13.3 min. Long term continuous recording is advantageous for the evaluation of the function of the sphincter of Oddi and short-term manometry may not be representative of overall sphincter of Oddi motility. PMID- 1914765 TI - Prophylactic use of OKT3 in liver transplantation. A review. AB - Liver rejection in the era of cyclosporine-based immunosuppression is approximately 60-70%. Approximately 15-25% of liver transplant patients will require hemodialysis following transplantation. These facts argue for a potent, less nephrotoxic immunosuppressive regimen, especially during the period of vulnerability to these events. Prophylactic use of OKT3 has been suggested as a means to decrease the need for hemodialysis while maintaining potent immunosuppression. The goal of this review is to examine potential benefits and pitfalls of this regimen. A lack of documentation of long-term patient and graft survival, the potential susceptibility to infectious complications, development of sensitization, and the cost must be weighed against the decreased need for hemodialysis and the control of early rejection episodes. PMID- 1914766 TI - Rejection therapies. AB - One hundred thirty-eight primary liver allograft recipients received cyclosporine and prednisolone immunosuppression with azathioprine added during the induction phase. All rejections were biopsy-confirmed clinical rejections. Acute rejection was seen in 58.7% of the patients. The treatment of acute rejection was successful in 88.9% of treated patients. Rejection-related death was seen in 4.3%, and retransplantation was performed for acute or chronic rejection in 2.2% of the patients. The risk for dying increased with the number of rejection treatments. PMID- 1914767 TI - Effect of nifedipine on interdigestive gallbladder volume and postprandial gallbladder emptying in man. AB - The effect of two oral doses (10 and 20 mg) of nifedipine versus placebo on the fasted gallbladder volume and on the meal-induced gallbladder emptying was assessed according to a double-blind study protocol in 12 healthy volunteers. Eight subjects underwent three studies (with placebo and with both nifedipine doses), whereas in two subjects the effect of a 10-mg nifedipine dose vs placebo and in two others the effect of a 20-mg nifedipine dose vs placebo was examined. The studies were performed on separate days, and the gallbladder volume was measured by means of real-time ultrasonography. Neither placebo nor 20 mg nifedipine per os elicited any significant change in the fasted gallbladder volume. With 10 mg nifedipine per os a significant increase in the interdigestive gallbladder volume was observed: 22.9 +/- 2.9 cm3 before and 26.2 +/- 3.2 cm3 after the drug receipt (P less than 0.005). A trend towards an inhibition of the postprandial gallbladder emptying was observed with 10 mg nifedipine per os without, however, reaching the level of statistical significance. Following 20 mg nifedipine per os, a marked delay in the meal-stimulated gallbladder emptying occurred, as reflected by a decrease in the gallbladder ejection fraction from 48.1 +/- 4.5% (placebo) to 26.4 +/- 5.0% (nifedipine) (P less than 0.02) at 30 min and from 54.0 +/- 3.6% (placebo) to 33.2 +/- 4.6% (nifedipine) (P less than 0.02) at 40 min after the test meal. We conclude that a therapeutic oral dosage of nifedipine has a significant relaxing effect on the human gallbladder. PMID- 1914768 TI - Frequency of hereditary nonpolyposis colorectal cancer in southern Alberta. AB - The frequency of hereditary nonpolyposis colorectal cancer was evaluated in a group of colorectal cancer patients under age 50 diagnosed in southern Alberta between 1973 and 1987. Families were identified as positive for this syndrome if three first-degree relatives in the kindred had colorectal cancer. Of the 390 patients with adenocarcinoma, 318 patients participated. The frequency of hereditary nonpolyposis colorectal cancer was 3.1% (12 families) in this group (Ci95 1.6-5.3%). Clinical characteristics reported on from the index patients include tumor location, Dukes stage at presentation, frequency of synchronous and metachronous tumors, frequency of second primaries, and survival. The 5- and 10 year actuarial survival was 86% and 69%, respectively. PMID- 1914769 TI - Oral colon lavage solutions containing polyethylene glycol may interfere with ELISA detection of tumor-associated antigens in colonic effluent. AB - Immunologic methods for detection of colorectal neoplasia based on examination of stool or colonic effluent are being developed. Most current oral lavage preparations contain polyethylene glycol (PEG), and if PEG adversely interferes with immunologic testing these tests may become less useful. We describe a decrease in sensitivity of ELISA for tumor-associated antigens (TAA) when effluent samples are diluted in PEG-electrolyte lavage solution, equivalent to a commonly used oral lavage solution based on PEG. Radioisotope-labeled antigen binding to plastic plates was decreased by dilution in the PEG lavage solution. Antigen binding, present in colonic effluent collected by the laxative purge method, was absent in effluent collected by PEG oral lavage from the same patient. We conclude that PEG and PEG-containing lavage solutions interfere with ELISA detection of TAA in colonic effluents. We speculate that the in vitro, and possibly the in vivo, effect occurs at the level of antigen binding to the plate either by a steric effect or alteration of charge by the nonpolar properties of PEG. PMID- 1914770 TI - Two-color immunofluorescence and flow cytometric analysis of lamina propria lymphocyte subsets in ulcerative colitis and Crohn's disease. AB - By using two-color immunofluorescence with fluorescein isothiocyanate (FITC) and phycoerythrin (PE)-labelled monoclonal antibodies and multiparameter flow cytometry, we investigated lamina propria lymphocyte subsets of patients with ulcerative colitis (UC) and Crohn's disease (CD). Leu-3/Leu-2 (CD4/CD8) ratio of lamina propria lymphocytes (LPL) of CD (mean +/- SD: 1.9 +/- 0.8, P less than 0.01) was significantly decreased compared with controls (3.3 +/- 1.1), because of an increased number of CD8+ lymphocytes. The majority of lamina propria CD4+ cells were CD4+, Leu-8- and CD4+, CD45R- both in controls and IBD tissue. Many lamina propria T lymphocytes were activated, expressing HLA-DR antigen not only in IBD but also in controls. NK cells defined by CD16 and CD 56 (3.0 +/- 1.4%, P less than 0.01) were significantly decreased in patients with UC compared with controls (6.5 +/- 3.0%). A low proportion of B cells in the intestinal mucosa expressed Leu-8 antigen and CD23 antigen. The proportion of activated B cells of LPL was high in IBD mucosa as well as normal mucosa. These findings suggest that local activation of B cells leads to the loss of the expression of Leu-8 antigen and CD23. PMID- 1914771 TI - Short-chain fatty acids induce reversible injury of porcine colon. AB - Carbohydrate malabsorption frequently results in an increased net production of organic acids by colonic microorganisms and an acidification of colonic contents. Colonic structure and function during and following mucosal exposure to acetate at various H ion concentrations was examined under both in vivo and in vitro conditions. An acetic acid dose and time-dependent injury of the surface epithelium sequentially resulted in (1) degeneration and extrusion of enterocytes and increased ion permeability (pH 5.0); (2) formation of subepithelial blisters and increased mucosal permeability to mannitol (pH 4.0), and (3) sloughing of surface epithelium and the abolition of active NaCl absorption (pH 3.0). Both acetate and lactate at pH 4.0 produced significantly greater injury than similarly acidified NaCl. Crypt cell structure and Cl secretory function were preserved, however, and migration of viable cells from adjacent crypts rapidly covered the denuded surface within 30-60 min of recovery. Normal structure and function were nearly restored in 2 hr. These results suggest that colonic mucosal injury is possible under conditions that may be present during carbohydrate malabsorption syndromes. They also provide evidence that the process of surface reepithelialization may be of central importance in the defense and repair of the colonic mucosa during such acid-induced injury. PMID- 1914772 TI - Effect of obesity on gastroesophageal resistance to flow in man. AB - Chronic (obesity) and acute intraabdominal pressure increases appear to favor gastroesophageal reflux, but the mechanism is not completely understood. We hypothesized that it could be due to an alteration in the resistance gradient between the stomach and the gastroesophageal junction, even increasing intragastric resistance above resistance at the gastroesophageal junction. Hence, we used a pneumatic resistometer to measure gastric and gastroesophageal resistance to flow in 11 lean healthy controls and eight morbidly obese individuals without gastroesophageal reflux disease. Resistance was quantified at rest and during acute intraabdominal pressure increases, both in the recumbent and sitting positions. We found that gastroesophageal junction resistance was higher than gastric resistance in lean as well as in obese subjects (P less than 0.001). In obese individuals both gastric and gastroesophageal junction resistance were increased (P less than 0.001), thus a normal gastric gastroesophageal junction resistance gradient was maintained. Body position did not modify resistance. Acute increases in intraabdominal pressure decreased the gastric-gastroesophageal junction resistance gradient similarly in obese and lean subjects. We conclude that obesity by itself does not appear to predispose to gastroesophageal reflux, but it creates intraabdominal conditions that may favor reflux whenever the gastroesophageal barrier becomes weakened. PMID- 1914773 TI - Is rectosigmoid response to food modulated by proximal colon stimulation? AB - Rectosigmoid motor activity and postprandial breath hydrogen levels were monitored in eight healthy males under basal conditions and for 3 1/2 hr after a meal (beefburger and breadroll and ice cream incorporating 20 g lactulose). Within minutes of ingestion there was a significant increase in motility index (P less than 0.05) and also an initial temporary rise in breath hydrogen. A late increase in motor activity occurred in seven of eight subjects 123 +/- 19 min after the meal and was temporally related to the beginning of a second, much larger rise in breath hydrogen (r = 0.99; P less than 0.01). The close association between the timing of the rises in breath hydrogen and rectosigmoid motor activity would support the possibility that the latter may be generated by chemical or mechanical stimulation of the proximal colon. PMID- 1914774 TI - Retention of nondeflating balloon in small bowel. Case report and review of the literature. AB - Intubation of the upper gastrointestinal tract with balloon catheters has a role in the diagnosis, treatment, and research of many gastrointestinal conditions. A potential complication of this procedure, albeit rare, is failure of the balloon to deflate, thereby preventing removal of the intestinal tube. We describe a case where this problem arose and the series of maneuvers that were attempted to resolve it. Attempts at overdistending the balloon, reaching it via endoscopy, and ultrasound localization of the balloon all failed. The tube was successfully removed following CT-guided percutaneous needle puncture of the impacted balloon. The published experience with nondeflating catheter balloons in hollow viscera has been reviewed and the suggested methods for deflation or puncture are discussed. PMID- 1914776 TI - Development of non-Hodgkin's lymphoma of the colon after radiation therapy for Hodgkin's disease. AB - Developments in the therapeutic approach to Hodgkin's disease have resulted in excellent long-term survival statistics. However, these patients are at risk for second malignancies, most commonly acute myelogenous leukemia and non-Hodgkin's lymphoma. We present a patient who developed non-Hodgkin's lymphoma of the colon simulating adenocarcinoma 14 years after successful radiation therapy for Hodgkin's disease. PMID- 1914775 TI - Oral contraceptive-induced esophageal ulcer. Two cases and literature review. AB - Two patients with esophageal ulcers following ingestion of oral contraceptives are presented. Without discontinuing the drug, but providing that the pills were correctly ingested, the ulcers completely healed. This new adverse side effect of oral contraceptive emphasizes once more what appears to be a never-ending problem due to the lack of awareness of the prescribing physician. PMID- 1914777 TI - Gastric "pseudolymphoma" with restricted light chain expression in a patient with obscure gastrointestinal blood loss. AB - We present a case report of a gastric "pseudolymphoma" (GL) that exhibits restricted light chain expression and, therefore, illustrates the dilemma encountered when histologically benign lesions have phenotypic abnormalities suggesting malignancy. For many years this lesion has been considered usually benign; however, recent reports such as this one demonstrate immunologic signs of monoclonality in an otherwise histologically benign lesion. This finding challenges our assumptions as to the nature of this lesion and our definition of cancer. The lesion also displays "Castleman-like" features (angiofollicular hyperplasia) as well as "common inflammatory" germinal centers. In addition we briefly review the literature. PMID- 1914778 TI - Extensive gastrointestinal aspergillosis associated with AIDS. PMID- 1914779 TI - Omeprazole: gastrin and gastric data (August 1991) PMID- 1914780 TI - Evaluation of a system for the delivery of inhaled beclomethasone dipropionate to intubated neonates. AB - Since systemic dexamethasone therapy for bronchopulmonary dysplasia is associated with numerous side effects, a simple system to deliver aerosolized beclomethasone dipropionate (BDP) directly to the lungs of intubated neonates was developed and evaluated in vitro. The system consists of a self-inflating bag, metered dose inhaler (MDI) adapter, Tygon spacer and endotracheal tube (ETT). A dose is delivered by discharging the MDI into the system and giving 3 'breaths' with the bag. Different sizes of ETT do not affect the drug output (1.17 +/- 0.29 vs. 1.32 +/- 0.34 micrograms of BDP per dose using a 3.0-mm or 3.5-mm ETT, respectively; means +/- SD). However, a shorter system spacer substantially reduces the drug output. The majority (54.0%) of the particles exiting the ETT and available to the patient are in the respirable range (0.5-5.5 microns). Based on adult doses and delivery of BDP and the relative sizes of the adult and neonatal lung, it is estimated that a neonate will require 1-6 doses/day. Replacing dexamethasone in the treatment of bronchopulmonary dysplasia with aerosol topical steroids delivered by this system may improve both the safety and efficacy. PMID- 1914781 TI - Chloral hydrate disposition following single-dose administration to critically ill neonates and children. AB - Although the metabolism and pharmacokinetics of chloral hydrate (CH) have been studied in healthy adults, no comprehensive studies have been done in neonates and young infants. Major physiological differences between these groups could greatly affect drug disposition. In this study the patient population (22 patients) was divided into three groups according to postconceptual age: group 1 = preterm infants (31-37 weeks), group 2 = fullterm infants (38-42 weeks) and group 3 = toddler-child patients (57-708 weeks). After receiving one 50 mg/kg oral dose of CH, the parent drug and its metabolites were determined by gas chromatography utilizing an electron capture detector. CH, contrary to what has been reported in the adult, was detectable for several hours after oral administration to patients in all three groups. A highly significant negative correlation was observed amongst the three groups for the half-life (t1/2) and area-under-the-curve for 0 to infinity values for trichloroethanol (TCE), the active metabolite responsible for the sedation effect. The t1/2 value for TCE in group 3 (9.67 h) was similar to that reported for the adult population, but in the less mature subjects it was approximately three (group 2: 27.8 h) to four times (group 1: 39.8 h) greater. Trichloroacetic acid had a remarkably long residence time in the study population after a single dose of CH. The concentration of this metabolite failed to decline even 6 days after dose. These issues should be carefully considered when CH administration is contemplated for clinical use in neonates, infants and children. PMID- 1914782 TI - Lack of a pharmacokinetic interaction between doxapram and theophylline in apnea of prematurity. AB - To examine the possibility of a pharmacokinetic interaction between doxapram and theophylline, both drugs (1.5 mg/kg/h doxapram, and 0.5 mg/kg/h theophylline) were administered in that order and in reverse order to patients with apnea of prematurity. During the therapeutic steady state phase of doxapram considerable serum theophylline concentrations were found despite discontinuation of the latter drug for at least 48 h. Serum doxapram concentrations during theophylline steady state were negligible. Pretreatments of theophylline failed to alter the pharmacokinetic indices of doxapram. Thus, a lack of pharmacokinetic interaction between the two drugs was demonstrated. PMID- 1914783 TI - Dopamine sulphotransferase is better developed than p-nitrophenol sulphotransferase in the human fetus. AB - The distribution patterns of two forms of sulphotransferase were studied in human adult and fetal tissues. One form was studied with p-nitrophenol as substrate and it is referred to as 'TS'. The other form was studied with dopamine as substrate and it is referred to as 'TL'. The activities of TS (pmol X min-1 X mg-1; mean +/ SD) were 1,077 +/- 293 (adult liver; n = 6), 97.8 +/- 26.4 (fetal liver; n = 8); 38.0 +/- 12.8 (adult kidney; n = 5), 28.5 +/- 21.5 (fetal kidney; n = 8); 78.9 +/ 21.3 (adult lung, ex-smokers; n = 5), 83.0 +/- 23.1 (adult lung, smokers; n = 5), 25.8 +/- 10.0 (fetal lung; n = 8), 140.8 +/- 18.9 (ileum; n = 5), 68.6 +/- 30.7 (ascending colon; n = 5), 28.6 +/- 10.8 (fetal gut; n = 8), 23.9 +/- 14.5 (placenta; n = 5). The adult to fetal ratios for TS were 11.0 (liver), 1.3 (kidney), 3.1 (lung) and 2.6 (gut). The activities of TL were 28.9 +/- 17.4 (adult liver; n = 6), 97.2 +/- 52.3 (fetal liver; n = 8); 10.3 +/- 4.7 (adult kidney; n = 5), 37.7 +/- 29.9 (fetal kidney; n = 8); 79.6 +/- 18.8 (adult lung, ex-smokers; n = 5), 76.3 +/- 23.7 (adult lung, smokers; n = 5), 98.2 +/- 55.0 (fetal lung; n = 8); 391.2 +/- 37.3 (ileum; n = 5), 161.5 +/- 66.0 (ascending colon; n = 5), 200.6 +/- 137.1 (fetal gut; n = 8), 21.8 +/- 13.6 (placenta; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914784 TI - Excitation-contraction coupling in neonatal myocardium: effects of halothane and isoflurane. AB - We evaluated the effects of halothane and isoflurane on force, action potential, and staircase, an indicator of sarcoplasmic reticulum function, in right ventricular papillary muscles from 4- to 8-day rabbits using a single sucrose gap myograph at a low baseline stimulating frequency of 12 min-1. The ED50 for depression of peak force was 0.25% for halothane and 0.54% for isoflurane. Both anesthetics were more depressant to neonatal myocardium than has been reported in adult myocardium. The ratio of ED50 in neonatal myocardium to that reported in adult myocardium was similar for both anesthetics (0.42 and 0.39). Both anesthetics decreased the height of the plateau phase of the action potential by an equivalent amount but neither affected action potential duration. PMID- 1914785 TI - Pharmacokinetic aspects of caffeine in premature infants. AB - The pharmacokinetic profile of caffeine was studied in 15 premature infants. Five infants received a single intravenous dose of 10 mg/kg of caffeine citrate 100% at birth and on the 15th day of life. Ten neonates were studied during daily therapy with caffeine for prophylaxis of idiopathic apnea. The time course of plasma and urinary concentrations of caffeine and theophylline shows that caffeine is transformed to theophylline at birth, while total urinary xanthines decrease significantly (p less than 0.001) 72 h after the loading dose given on the 15th day of life. During the whole period of treatment, the decrease in total urinary xanthines and the constant urinary percentage elimination of theophylline are due to further metabolism of theophylline. We confirm that the intravenous loading dose of 10 mg/kg can rapidly obtain therapeutic blood levels of caffeine. We also confirm that the maintenance therapy can be carried out with a single daily dose. PMID- 1914786 TI - Disposition of cocaine in pregnant sheep. I. Pharmacokinetics. AB - Cocaine abuse by pregnant women is increasingly recognized as causing serious health consequences for mother and newborn. To assess the placental transfer and fetal effects of cocaine, we studied its pharmacokinetics following intravenous administration to the pregnant ewe and fetus. Following bolus doses of 0.5-4.0 mg/kg to ewes, cocaine appeared within 30 s in fetal circulation, with peak concentrations occurring in 4-5 min. The disappearance of cocaine in the fetal plasma paralleled that in maternal plasma, suggesting that a rapid equilibrium of cocaine occurred between maternal and fetal compartments. The mean half-life of cocaine in the fetus across doses (4.4-5.0 min) was similar to that in the ewe (4.0-5.6 min). Plasma clearance of cocaine in the ewe did not appear to vary according to dose. The fetal exposure to cocaine, as indicated by the area under the fetal plasma concentration versus curve, was a linear function of maternal cocaine dose (r = 0.96, p less than 0.01). These results demonstrate rapid placental transfer of cocaine after maternal administration in an animal model and rapid metabolism by mother and fetus. PMID- 1914787 TI - Disposition of cocaine in pregnant sheep. II. Physiological responses. AB - We studied maternal and fetal blood pressure, heart rate, arterial blood gases and fetal behavioral state alterations in response to maternally administered cocaine hydrochloride in 11 pregnant sheep. Cocaine administration to the ewe caused a dose-dependent increase in maternal blood pressure and heart rate and in fetal blood pressure, and a decrease in fetal arterial oxygen tension. In the ewe, blood pressure changes corresponded linearly to dose administered (r = 0.88, p less than 0.001). Blood pressure changes were correlated to peak plasma cocaine concentration in the ewe (r = 0.52, p less than 0.01) and in the fetus (r = 0.43, p = 0.05). In addition, in 7 of 8 fetuses which had entered rapid eye movement (REM) sleep within 5 min of maternal cocaine administration, REM sleep was abruptly terminated either by the cocaine, fetal hypoxia or some other nonspecific event caused by the maternal cocaine administration. Maternal cocaine administration causes maternal and fetal hemodynamic alterations that have potential adverse effects in pregnancy. PMID- 1914788 TI - Gene expression, ontogeny and transplacental induction of hepatic UDP glucuronosyl transferase activity in mice. AB - The ontogeny and transplacental inducibility of UDP-glucuronosyl transferase (UDPGT) activities potentially relevant to detoxification of polycyclic aromatic hydrocarbons were studied in (C57BL/6 x DBA/2) F1 or (DBA/2 x C57BL/6) F1 fetal mouse liver, with p-nitrophenol (PNP) and 3-hydroxybenzo[a]pyrene (3-OH-BP) as substrates. Both UDPGT activities developed during the late fetal period and reached almost 60% of the adult activity at term; PNP, but not 3-OH-BP UDPGT decreased significantly on postnatal day 1 before rising to adult levels. A single exposure to beta-naphthoflavone (beta NF; 150 mg/kg) on day 17 of gestation induced the PNP-UDPGT activity significantly (1.5-fold) by day 19 in the B6D2 F1s but not D2B6 F1s. A single dose of 3-methylcholanthrene (MC; 100 mg/kg) or 2,3,7,8,-tetrachlorodibenzo-p-dioxin (10 micrograms/kg) did not induce, but three injections of MC also resulted in significant induction in the fetuses of C57BL/6 mothers. 3-OH-BP-UDPGT was not significantly induced by any of the chemicals in either genetic cross. In a parallel study, a gene for an inducible mouse UDPGT, designated UDPGTm-1, was shown by Northern blotting to be expressed in fetal liver by day 18 of gestation at low levels relative to adults, but was not induced transplacentally by MC, beta NF or phenobarbital (PB). These results show that (1) at least two functionally defined UDPGT activities toward phenolic substrates are present in the late fetal mouse liver; (2) one of these is transplacentally inducible by beta NF and MC, but only in fetuses of C57BL/6 mothers, (3) induction where achieved was relatively small in magnitude, and (4) a gene of a PB-inducible UDPGT was expressed at low levels in the fetuses but was not induced transplacentally. PMID- 1914789 TI - Postnatal changes in the insulin-depleting action and disposition of cyproheptadine in rats. AB - The relationship between age-related differences in cyproheptadine (CPH)-induced alteration of endocrine pancreas function and the disposition of the drug was examined in this study. Various doses of CPH (5, 11, 22.5 or 45 mg/kg) were given orally once daily for 2 days to 10-, 15-, 25- and 50-day-old rats. Pancreatic and serum insulin measured 24 h after the second dose showed a drug-dependent decline, and the extent of this effect was dependent on the dose administered and the age of the animal. In 50-day-old rats, a significant reduction in pancreatic and serum insulin was detected only after high doses (22.5 and 45 mg/kg) of the drug. However, in 10- and 15-day-old rats, the effects were observed after the lowest dose (5 mg/kg). In separate experiments, the concentrations of CPH and its active metabolites, desmethylcyproheptadine (DMCPH), desmethylcyproheptadine 10,11-epoxide (DMCPH-epoxide) and cyproheptadine-10,11-epoxide (CPH-epoxide), were measured in the pancreas, liver and lung of neonatal and young rats at various times after the second dose of CPH (11 mg/kg). In the younger age groups (10- and 15-day-olds), there were significantly higher tissue levels of unchanged drug at all times examined. Certain of the drug metabolites known to be inhibitors of insulin synthesis had higher and/or more prolonged tissue concentrations in younger animals. For example, the metabolite CPH-epoxide was found only in tissues from younger age groups. Twenty-four hours after the second dose of CPH, no drug-derived product was present in tissues of 25- and 50-day-old rats, whereas significant amounts of DMCPH-epoxide, a potent CPH metabolite inhibiting insulin synthesis, was detected in the tissues of 10- and 15-day-old rats. The data show that there are age-related differences in the susceptibility of pancreatic B cells to the actions of CPH, and that these differences are associated with age-related changes in the disposition of the drug. PMID- 1914790 TI - CO2 breath tests using 14C-caffeine, 14C-methacetin and 14C-phenacetin for assessing postnatal development of monooxygenase activities in rats and marmosets. AB - The time course in which the activities of cytochrome P450-dependent drug metabolizing enzymes develop during the perinatal period differs for various types of monooxygenases as well as for various animal species. Using [3 methyl14C]-, [7-methyl14C]-caffeine, [14CH3]-methacetin and [14C2H5]-phenacetin as substrates in breath tests, the developmental changes in the rates of 14CO2 formation, due to changes in the activity of monooxygenases, were studied in rats and marmoset monkeys (Callithrix jacchus). In rats a rate of 0.006% of the dose administered/min was found to be exhaled as 14CO2 in the caffeine breath tests on the 1st day of life. This value increased gradually reaching adult rates of 14CO2 exhalation after 21 days for [3-methyl14C]-caffeine and after 25 days for [7 methyl14C]-caffeine. In marmosets the rate of 14CO2 exhalation for [3-methyl14C]- and [7-methyl14C]-caffeine was also low at birth and developed gradually reaching adult values of 14CO2 exhalation within 120-200 days. In rats the capacity for dealkylation of methacetin and phenacetin developed much faster compared with caffeine: 9 days postnatally, the exhalation of 14CO2 reached adult values. Offspring of marmosets reached adult values of 14CO2 exhalation at 8 days postnatally when using [14CO2]-methacetin as substrate and at 30 days postnatally using [14C2H5]-phenacetin in the breath test. The results suggest that the monooxygenases for the N-demethylation of caffeine, the O-demethylation of methacetin and the O-deethylation are rather substrate specific in the two species studied. The breath tests used are sensitive methods for assessing the development of different monooxygenases in vivo in rats and marmosets, and they may well (using 13C-labelled substrates) be applicable for studies in children to monitor effects of certain environmental pollutants. PMID- 1914791 TI - Induction of hepatic bilirubin-metabolizing enzymes by the traditional Chinese medicine yin zhi huang. AB - Daily administration of either phenobarbital (60 mg/kg) or yin zhi huang (YZH, 30 60 ml/kg) for 5 days to rats similarly accelerated the clearance and conjugation of intravenously infused bilirubin. However, the two drugs had quite different effects on liver enzyme activities associated with xenobiotic metabolism and with bilirubin metabolism. Phenobarbital markedly increased cytochrome P-450 levels and the cytochrome-P-450-mediated formation of 4-hydroxybiphenyl whereas YZH had a slightly depressive effect on this enzyme system. Both drugs increased glucuronyl transferase activity using bilirubin and alpha-naphthol as substrates. Bilirubin conjugation in microsomes activated by uridine diphosphate-N acetylglucosamine (NAG) was greater in YZH- than in phenobarbital-treated rats whereas phenobarbital was a more effective inducer in digitonin-activated enzyme. When alpha-naphthol was used as substrate (NAG-activated glucuronyl transferase), pretreatment with phenobarbital produced a greater increase in activity than did YZH. Glutathione-S-transferase activity (using chlorodinitrobenzene as substrate) was increased more than 2-fold by phenobarbital but only slightly (1.29 X) by YZH. In contrast, YZH (60 ml/kg) was more effective than phenobarbital in increasing glutathione peroxidase activity using cumene hydroperoxide as substrate. YZH appears to be a relatively specific inducer of enzymes involved in bilirubin metabolism. PMID- 1914792 TI - Trends in prevalence of diabetes mellitus in patients with myocardial infarction and effect of diabetes on survival. The Minnesota Heart Survey. AB - OBJECTIVE: The purpose of this study was to document trends in the prevalence of diabetes among men and women hospitalized for myocardial infarction (MI) and to determine the effect of diabetes on in-hospital case fatality rates and long-term survival. RESEARCH DESIGN AND METHODS: The Minnesota Heart Survey is a population based surveillance system that has monitored trends in coronary heart disease morbidity since 1970. As part of this effort, a 50% random sample of acute MI discharge records in Minneapolis-St. Paul metropolitan area hospitals was abstracted in 1970, 1980, and 1985. RESULTS: The prevalence of diabetes among MI patients was compared over time, and the data indicated a significant increase between 1970 and 1985 in both men (8.2 vs. 16.8%, P less than 0.001) and women (16.0 vs. 25.8%, P = 0.01). Diabetic individuals had an odds ratio of in-hospital death after an MI 1.5 times that of nondiabetic individuals (P less than 0.01) after controlling for the effects of sex, age, and year of MI. Among discharged MI survivors, the risk of death was 40% higher (P less than 0.01) in diabetic individuals than nondiabetic individuals after 6 yr of follow-up. Compared with nondiabetic individuals, diabetic individuals appeared more likely to have cardiac (pump) failure with acute MI. CONCLUSIONS: Our findings suggest that the risk of coronary heart disease morbidity and mortality attributable to diabetes may be increasing over time. Therefore, clinicians need to take extra care in the management of MIs in diabetic individuals, and public health efforts to reduce diabetes prevalence are warranted. PMID- 1914794 TI - Kinetics of zinc status in children with IDDM. AB - OBJECTIVE: To ascertain zinc deficiency in patients with insulin-dependent diabetes mellitus (IDDM) and evaluate the relationship between zinc clearance and body height velocity. RESEARCH DESIGN AND METHODS: Six boys and 11 girls with IDDM and zincuria and glycosuria were studied. Study quality and specific descriptive information concerning relationship and outcome measurement were assessed. RESULTS: The values of total-body zinc clearance in IDDM patients were higher than in the control subjects (24.6 +/- 1.8 vs. 15.1 +/- 0.6 ml.kg-1.h-1, P less than 0.01). There was a negative correlation between body zinc clearance values and height velocity in IDDM patients. CONCLUSIONS: Patients with IDDM have a secondary zinc deficiency, and normal growth may be stunted. PMID- 1914793 TI - Hypoglycemia due to surreptitious injection of insulin. Identification of insulin species by high-performance liquid chromatography. AB - OBJECTIVE: To identify the circulating species of insulin after separation by high-performance liquid chromatography (HPLC) in patients with factitious hypoglycemia. RESEARCH DESIGN AND METHODS: In three of four patients presented, the diagnosis of surreptitious insulin injection was made by documenting the presence of animal insulin in the circulation after separation of the circulating insulin forms by HPLC. RESULTS: Animal insulin was identified. CONCLUSIONS: Thus, the identification of the circulating form of insulin in the circulation by HPLC may be a useful adjunct in the diagnosis of factitious hypoglycemia if animal insulin has been injected and if the simultaneously measured concentrations of insulin and C-peptide are inconclusive. PMID- 1914795 TI - Epidemiology of childhood IDDM in U.S. Virgin Islands from 1979 to 1988. Evidence of an epidemic in early 1980s and variation by degree of racial admixture. AB - OBJECTIVE: The epidemiology of insulin-dependent diabetes mellitus (IDDM) was evaluated in a predominantly black population in the U.S. Virgin Islands. RESEARCH DESIGN AND METHODS: Primary ascertainment of diabetic subjects was by retrospective review of hospital and clinic records, and IDDM was defined by Diabetes Epidemiology Research International Group criteria. RESULTS: For the period 1979-1988, 28 children less than 15 yr of age were diagnosed with IDDM resulting in an average annual IDDM incidence rate (IR) of 7.5/100,000 (95% confidence interval 4.7-10.3). A significant increase in IDDM incidence (P less than 0.01) was observed when the IR rose to 28.4/100,000 in 1984. White children had the highest IR (28.9/100,000). The IR for Hispanics (7.2/100,000) was slightly higher than that for blacks (5.9/100,000). Among black children, a slight but nonsignificant male excess in incidence was observed (male-female ratio 1.5). When black or Hispanic patients were compared with age-matched control subjects with respect to grandparental race, the diabetic subjects had a greater percentage of white ancestry (P less than 0.02 and P less than 0.05, respectively). The incidence of IDDM in Caribbean blacks (West Indians) in the U.S. Virgin Islands was similar to blacks in the U.S. CONCLUSIONS: The epidemic of IDDM in 1984 provides support for a possible pandemic in the early 1980s. PMID- 1914796 TI - Accuracy of blood glucose estimation by children with IDDM and their parents. AB - OBJECTIVE: To evaluate the accuracy of blood glucose symptom recognition and subjective blood glucose estimation in insulin-dependent diabetic (IDDM) children and their parents. RESEARCH DESIGN AND METHODS: Blood glucose estimation questionnaires were completed 4 times/day at home during routine activities. A sequential sample of 19 families, who attended a pediatric diabetes clinic, with IDDM children less than 12 yr old and IDDM duration of greater than or equal to 9 mo comprised the study. RESULTS: Error grid analysis showed that both children and parents demonstrated poor accuracy, making clinically significant errors as frequently as clinically accurate estimates. The most common error was the failure to detect extreme blood glucose levels, with a significant tendency to underestimate hyperglycemia. Children often reported hypoglycemia when blood glucose was hyperglycemic. Confidence in the ability to estimate blood glucose was unrelated to measured accuracy. CONCLUSIONS: IDDM children and their parents demonstrated a higher rate of blood glucose estimation errors than IDDM adolescents and adults in previous studies. Even in families who use self monitoring of blood glucose frequently, self-reported ability to recognize symptoms and estimate blood glucose should be viewed with caution. Families with IDDM children need more education about errors in symptom recognition and blood glucose estimation. They should also be encouraged to use self-monitoring of blood glucose before treating children's reported hypoglycemic symptoms whenever possible. PMID- 1914797 TI - Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects. AB - OBJECTIVE: To compare postprandial glucose excursions and plasma free insulin analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). RESEARCH DESIGN AND METHODS: Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. RESULTS: Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). CONCLUSIONS: Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future. PMID- 1914798 TI - Use of fructosamine test in diabetic children. AB - OBJECTIVE: The goal of this study was to assess the effect of glucose and the contribution of the aldimine component on the measurement of fructosamine, the relationship of serum fructosamine with glycosylated plasma proteins, as measured by a new high-performance liquid chromatography methodology (Glyc PP-HPLC) and by an affinity chromatography (Glyc PP), and the ability of serum fructosamine to assess acute, short-term (1-2 wk), and long-term (2-3 mo) glycemic control. RESEARCH DESIGN AND METHODS: The measurement of fructosamine was unaltered by the addition of up to 27.5 mM glucose or by the elimination of the aldimine component of serum specimens by dialysis. Fructosamine was generated in vitro by incubating serum aliquots. This generation was dependent on time, glucose concentration, and temperature. RESULTS: Fructosamine (n = 27) correlated well with Glyc PP (r = 0.76, P less than 0.01) and significantly less with Glyc PP-HPLC (r = 0.46, P less than 0.01). Although oral glucose ingestion increased serum glucose acutely by 200%, fructosamine was unchanged at each time interval. Improving glycemic control decreased the mean serum fructosamine concentration from 3.68 (baseline) to 3.28 mM (P less than 0.01) at 1 wk and to 3.13 mM (P less than 0.01) at 2 wk. HbA1c correlated with fructosamine (r = 0.59) and Glyc PP-HPLC (r = 0.47) but correlated best with Glyc PP (r = 0.83). CONCLUSIONS: These results indicate the fructosamine assay is unaltered by serum glucose, solely measures the ketoamine component, correlates well with glycosylated plasma proteins measured by aminophenylboronic acid column chromatography, is unaffected by acute changes of serum glucose, and may be used to monitor changes in glycemic control over a 1-wk interval. PMID- 1914799 TI - Learning to empower patients. Results of professional education program for diabetes educators. AB - The patient empowerment approach to diabetes education is intended to enable patients to make informed decisions about their own diabetes care and to be fully responsible members of the health-care team. Facilitating patient empowerment requires a specific set of skills and attitudes on the part of diabetes educators. A professional education program designed to facilitate the acquisition and enhancement of the requisite skills and attitudes was designed, implemented, and evaluated. The program involved adhering to a simulated diabetes care regimen for 3 days followed by a 3-day intensive skills-based workshop. The 23 educators who participated in the first two offerings of this program made significant gains in their counseling skills and demonstrated a positive change in attitude. PMID- 1914800 TI - Microalbuminuria. Invalidity of simple concentration-based screening tests for early nephropathy due to urinary volumes of diabetic patients. AB - OBJECTIVE: To evaluate the possibility of replacing quantitative albumin excretion rate (AER) measurements with rapid screening tests for microalbuminuria. RESEARCH DESIGN AND METHODS: Dipstick-negative specimens from 363 consecutive insulin-dependent diabetes mellitus (IDDM) and 46 non-insulin dependent diabetes mellitus (NIDDM) patients from primary-care and hospital clinics (11% inpatients) within the district of Turku University Hospital were studied. Albumin concentrations and 12-h nightly excretion rates (N-AER) were measured by nephelometry (sensitivity 2 mg/L). RESULTS: An increased N-AER (greater than 15 micrograms/min) was seen in 99 IDDM (27%) and 15 NIDDM (33%) patients. The median urinary volume was 900 ml/12 h, with a maximum of 3000 ml. At the level of 20 mg albumin/L, the sensitivity to detect elevated N-AER was 70% among IDDM patients and 60% among NIDDM patients. At a lower albumin concentration of 10 mg/L, the sensitivities were increased to 91 and 87% in IDDM and NIDDM patients, respectively, but the specificities were reduced to 77 and 71%, respectively. CONCLUSIONS: To evaluate incipient nephropathy, we recommend quantitative measurements of N-AER from timed urine collections only. Dipstick tests are either insensitive or nonspecific. PMID- 1914801 TI - Psychological responses of obese type II diabetic subjects to very-low-calorie diet. AB - OBJECTIVE: Very-low-calorie diets have been shown to produce dramatic improvements in glycemic control in obese subjects with non-insulin-dependent (type II) diabetes. There have been no studies of the psychological responses of diabetic subjects to these diets. RESEARCH DESIGN AND METHODS: This study examined changes in hunger, depression, and anxiety in 33 obese type II diabetic subjects who were randomly assigned to behavior modification programs that used either a balanced diet of 4185-6277 J/day (1000-1500 cal/day) throughout or included an 8-wk period of a very-low-calorie diet (1674 J/day or 400 cal/day of lean meat, fish, or fowl). Subjects completed the Beck Depression Inventory, the Spielberger State Anxiety Questionnaire, and self-report measures of hunger frequently throughout the 20-wk program. RESULTS: Both groups experienced significant improvements in depressive symptomatology, anxiety, and lessening of hunger during the course of the program, with no significant differences observed between the balanced diet and the very-low-calorie diet groups. CONCLUSIONS: Very low-calorie diets, used in the context of a behavioral weight-control program, result in reductions in hunger and improvements in mood state comparable to those observed on more moderate weight-loss regimens. PMID- 1914802 TI - Clinic attendance and glycemic control. Study of contrasting groups of patients with IDDM. AB - OBJECTIVE: To assess factors associated with attendance at a specialized clinic for diabetes care. RESEARCH DESIGN AND METHODS: Adults with insulin-dependent diabetes mellitus (IDDM) in poor (HbA1 greater than or equal to 12%) versus good (HbA1 less than or equal to 10%) control and with no known complications comprised the study group. RESULTS: Infrequent attenders were in worse glycemic control than regular attenders (chi 2 = 6.60, P less than or equal to 0.01) and held health beliefs that downplayed the importance of getting advice from physicians (P less than or equal to 0.002) or providing opinions to physicians about what might be done to improve their health (P less than or equal to 0.001). CONCLUSIONS: Because infrequent attenders are more likely to be in poor glycemic control and thus at greater risk for diabetic complications, engaging them in regularly supervised treatment has important personal and public health implications. Additional studies are needed to understand why some diabetic patients limit their contact with medical providers and to develop more effective strategies for reversing this process. Initial findings from this study suggest that patient beliefs about the doctor-patient relationship may influence clinic attendance. PMID- 1914803 TI - Evaluation of new computerized method for recording 7-day food intake in IDDM patients. AB - OBJECTIVE: To evaluate a new computerized method for recording 7-day food intake. RESEARCH DESIGN AND METHODS: Randomized crossover trial was conducted with patients recording the amount and type of every food and drink consumed during a week by either a computerized device (Food-meter) or recording the data in a diary. Each method was applied twice. Twenty-one insulin-dependent diabetic patients (mean +/- SD age 25 +/- 9 yr) were studied. RESULTS: The two methods showed very good agreement in the evaluation of the patients' diets (1792 +/- 408 vs. 1764 +/- 436 kcal/day, 84 +/- 19 vs. 82 +/- 21 g/day protein, 68 +/- 22 vs. 67 +/- 23 g/day fat, 210 +/- 60 vs. 207 +/- 58 g/day carbohydrate with the conventional and computerized methods, respectively). The variability between the methods and the variability within each method were of similar magnitude. CONCLUSIONS: The Food-meter represents a useful tool for computerizing the 7-day food record. The method is easy, reliable, and time saving. Moreover, it minimizes the risk of transcriptional errors. PMID- 1914804 TI - Barriers to improving diabetes care for blacks. PMID- 1914805 TI - Too uptight about tight control? PMID- 1914806 TI - Illegible fingerprints. PMID- 1914807 TI - Classification of diabetes according to National Diabetic Data Group. PMID- 1914808 TI - Let's not forget IDDM in African-American children. PMID- 1914809 TI - Computer program for IDDM registries. PMID- 1914810 TI - Diabetes in Hispanic Americans. Introduction. PMID- 1914812 TI - Prevalence of diabetes in Mexican Americans, Cubans, and Puerto Ricans from the Hispanic Health and Nutrition Examination Survey, 1982-1984. AB - The purpose of this study was to estimate the prevalence of diagnosed and undiagnosed diabetes among Mexican Americans, Cubans, and Puerto Ricans in the United States and compare these estimates to data from prior surveys for U.S. non Hispanic whites and blacks. Data for this study are from the Hispanic Health and Nutrition Examination Survey, a multipurpose cross-sectional survey of three U.S. Hispanic populations conducted in 1982-1984. The interviewed sample of people aged 20-74 yr included 3935 Mexican Americans in the southwest, 1134 Cubans in Florida, and 1519 Puerto Ricans in the New York City area. The diabetes component consisted of interview questions on diabetes diagnosis and treatment and an oral glucose tolerance test administered to a subsample. The prevalence of diabetes was two to three times greater for Mexican Americans and Puerto Ricans than for non-Hispanic whites surveyed in 1976-1980. In Cubans, the prevalence was similar to that for non-Hispanic whites. In men and women 45-74 yr of age, the prevalence of diabetes was extremely high for both Mexican Americans (23.9%) and Puerto Ricans (26.1%) compared with Cubans (15.8%) or non-Hispanic whites (12%). The total prevalence of diabetes was not significantly different for Mexican Americans and Puerto Ricans but was significantly lower for Cubans. The relatively lower prevalence of diabetes among Cubans and the high prevalence in both Mexican Americans and Puerto Ricans may be related to socioeconomic, genetic, behavioral, or environmental factors. PMID- 1914811 TI - Origins of U.S. Hispanics. Implications for diabetes. AB - The purpose of this article was to characterize the origins of the United States Hispanic population and discuss the implications of these origins in the context of diabetes risk. Particular attention was focused on the genetic origins of the three major U.S. Hispanic groups, i.e., Mexican Americans, Puerto Ricans, and Cubans. The U.S. Census figures provided basic demographic information. Genetic marker data for ancestral populations were taken from a review of the literature and compendia. Genetic marker data for the Puerto Rican and Cuban populations were extracted from the literature. Genetic markers determined on approximately 1000 randomly selected Mexican Americans from Starr County, Texas, were taken as representative of the Mexican-American population. The Hispanic population is the second largest and fastest growing minority in the U.S. Estimates of the Hispanic population in 1988 indicated some 19.4 million residents, of whom 62% were classified as Mexican, 13% as Puerto Rican, and the remaining 25% as Cubans and others. Various lines of evidence can be used to characterize the Hispanic population and its origins. These include ethnohistory, self-assessment of ancestry, surname distributions, speech and cultural characteristics, quantitative traits, and genetic structure. Genetic data were used to estimate the contribution of putative ancestral populations to the contemporary gene pool. For Mexican Americans, 31% of the contemporary gene pool is estimated to be Native American derived, whereas 61 and 8% are Spanish and African derived, respectively. In Puerto Rico, the percentage of contributions of Spanish, Native American, and African admixture to the population are 45, 18, and 37%, respectively. For Cuba, the parallel estimates are 62, 18, and 20%. The high frequency of Native American-derived genes in the contemporary Hispanic population predict a higher frequency of non-insulin-dependent diabetes mellitus (NIDDM) under the assumption that genes are important in NIDDM etiology. Our results are consistent with the finding of the significant role of genes in determining risk. PMID- 1914813 TI - Epidemiological correlates of NIDDM in Hispanics, whites, and blacks in the U.S. population. AB - Characteristics, prevalence, and risk factors for non-insulin-dependent diabetes mellitus (NIDDM) among Hispanics, blacks, and whites aged 20-74 yr in the United States population were investigated with two national surveys that used a household interview to ascertain diagnosed diabetes and a 75-g 2-h oral glucose tolerance test to measure undiagnosed diabetes. The Hispanic Health and Nutrition Examination Survey of 1982-1984 studied Mexican Americans in the southwest U.S., Cuban Americans in the Miami, Florida, area, and Puerto Ricans in the New York City area. The National Health and Nutrition Examination Survey of 1976-1980 examined a national sample of U.S. residents, of whom data on blacks and whites were analyzed. People with diagnosed diabetes in the five populations were similar with respect to mean age (53-57 yr), age at diagnosis (45-48 yr), duration of diabetes (6.9-8.7 yr), and diabetes therapies (58-67% using pharmacological treatment). Mean age of people with undiagnosed diabetes (51-59 yr) was comparable to that of diagnosed cases, and mean fasting (7.1-7.8 mM) and 2-h postchallenge plasma glucose (14.1-15.5 mM) values for people with undiagnosed diabetes were similar among the five populations. However, obesity levels varied by race, sex, and whether diabetes was diagnosed or undiagnosed. Age-standardized prevalence of diabetes (sum of diagnosed and undiagnosed cases) was 6.2% in whites, 9.3% in Cubans, 10.2% in blacks, 13% in Mexican Americans, and 13.4% in Puerto Ricans. Thus, compared to whites, diabetes rates were 50-60% higher among Cubans and blacks and 110-120% higher among Mexican Americans and Puerto Ricans. Age-standardized rates of impaired glucose tolerance were similar among the five populations (10.3-13.8%). Increasing age, obesity, and family history of diabetes were associated with higher rates of diabetes but sex, physical activity, education, income, and acculturation were not risk factors or were only weakly associated with diabetes prevalence. PMID- 1914814 TI - Genetic and environmental determinants of type II diabetes in Mexican Americans. Is there a "descending limb" to the modernization/diabetes relationship? AB - Evidence from migrant population studies and secular trend data indicates that environmental factors play a role in the etiology of non-insulin-dependent (type II) diabetes. These environmental factors appear to be concomitants of the process whereby traditional populations become "modernized" or "westernized" and include increased intake of total calories, fat, and sucrose, decreased intake of total and complex carbohydrates, including fiber, and decreased physical exercise. There also appears to be a "postmodernization" process, which we have characterized as the "descending limb of the curve." In Mexican Americans in San Antonio, the prevalence of type II diabetes declines with acculturation to the values, attitudes, and behaviors of "postmodernized" American society. However, examination of the dietary and exercise concomitants of this process revealed a mixed picture. There was some suggestion that Mexican-American women, although not men, had entered onto the descending limb of the curve. However, Native American genetic admixture in Mexican Americans also covaried with affluence and acculturation in such a way that the declining prevalence of diabetes could as easily be due to genetic factors as to environmental factors. The "pancreatic exhaustion" theory holds that resistance to insulin action is a principal lesion leading to hypersecretion of insulin, hyperinsulinemia, and eventual islet cell failure and clinical diabetes. This theory predicts that prediabetic subjects will be hyperinsulinemic. In conformity with this theory, we have shown that subgroups of the Mexican-American population, defined on the basis of family history of diabetes, who would be expected a priori to be enriched with prediabetic subjects, are hyperinsulinemic as predicted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914815 TI - Microvascular complications of NIDDM in Hispanics and non-Hispanic whites. San Luis Valley Diabetes Study. AB - The goal of this article was to examine the differences in the rates of microvascular complications of non-insulin-dependent diabetes mellitus (NIDDM) in Hispanic and non-Hispanic white subjects. This was a geographically based case control study where prevalent cases of NIDDM were identified in medical records. Subjects attended a 4-h clinic to confirm NIDDM diagnosis and assess complication end points. Retinopathy was defined by stereofundus photographs. Distal symmetric neuropathy was determined by standardized clinical examination. Nephropathy was indicated by serum creatinine level, urine protein-creatinine ratio, and urine albumin concentration. This study consisted of 279 NIDDM subjects confirmed by oral glucose tolerance test and World Health Organization criteria aged 20-74 yr (187 Hispanic and 92 non-Hispanic white subjects). Duration-adjusted prevalence of retinopathy was significantly higher in non-Hispanic white subjects (54.1 per 100, 95% confidence interval [CI] 44.4-63.7) than in Hispanics (41.8 per 100, 95% CI 34.8-48.8). This excess occurred only in non-Hispanic white subjects with background retinopathy but not in those with more severe retinopathy. Hispanics and non-Hispanic white subjects did not differ significantly for the prevalence of neuropathy (31.6 per 100 in non-Hispanic white subjects and 26.3 per 100 in Hispanics) or nephropathy by any measure. There were no significant differences in duration of diabetes or mean glycohemoglobin levels between ethnic groups. Microvascular complications of NIDDM are not in excess among Colorado Hispanics, and retinopathy may be somewhat more common in non-Hispanic white people. PMID- 1914816 TI - Macrovascular complications in Mexican Americans with type II diabetes. AB - Mexican Americans have a threefold greater prevalence of non-insulin-dependent (type II) diabetes mellitus than non-Hispanic whites in the San Antonio Heart Study, a population-based study of diabetes. In addition, Mexican-American diabetic subjects (n = 365) have greater fasting glycemia than non-Hispanic white diabetic subjects (P less than 0.001). Despite these findings, and despite a higher prevalence of microvascular complications among Mexican Americans, there does not appear to be a marked difference in prevalence of macrovascular complications between Mexican-American and non-Hispanic white diabetic subjects. Mexican-American diabetic subjects have only a moderate excess of peripheral vascular disease (as judged by ankle-arm blood pressure ratios) relative to non Hispanic white diabetic subjects (sex-adjusted Mantel-Haenszel odds ratio 1.84, 95% confidence interval 0.75-4.49). Mexican-American diabetic subjects actually reported fewer myocardial infarctions than non-Hispanic white diabetic subjects (sex-adjusted Mantel-Haenszel odds ratio 0.73, 95% confidence interval 0.31 1.71). Duration was not associated with either peripheral vascular disease or myocardial infarction. Severity of glycemia was only mildly associated with presence of peripheral vascular disease and negatively associated with self reported myocardial infarction. This latter finding may represent a survival bias in that more severe diabetic subjects have already died and are not ascertained in a prevalence study. The absence of an ethnic difference in the prevalence of macrovascular disease contrasts with our previous reports from the San Antonio Heart Study, in which the prevalence of both retinopathy and proteinuria was observed to be higher in Mexican-American diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914817 TI - Diabetes mellitus in Mexico. AB - Diabetes in Mexico is a public health problem with considerable medical, social, and economic consequences. Although detailed data on the prevalence of diabetes and its complications are not available, health services utilization data of the Social Security organization (Instituto Mexicano del Seguro Social) indicate increasing use of primary and tertiary care for diabetes over a recent 10-yr period. A health interview survey conducted in 1988 indicated that, in different areas, from 3.5 to 12.7% of people aged greater than or equal to 65 yr are believed to have diabetes, and that rates are higher in many of the states bordering the United States. Diabetes ranks among the leading 10 causes of death throughout the country. Although the ranking varies from state to state and the diagnosis may not appear on the death certificate when death results from a complication of the disease, in 1983 diabetes was the leading cause of death in Mexico and the first or second leading cause in many of the states bordering the U.S. Gestational diabetes contributes to perinatal mortality, and in view of the high birth rates, represents an important facet of the disease in Mexico. The impact of specific complications of diabetes on morbidity and mortality in Mexico are not well delineated. The relative frequency and impact of insulin-dependent and non-insulin-dependent diabetes in Mexico are not known. PMID- 1914818 TI - Prevalence rates for diabetes mellitus in Puerto Rico. AB - The aim of this study was to analyze prevalence data for diabetes mellitus obtained from a household interview of a random sample of the general population by the Department of Health of the Commonwealth of Puerto Rico for the years 1975 1986. Details of the prevalence rate by sex and age were analyzed for the years 1981, 1984, 1985, and 1986 and for the urban and rural population in 1985. The mean prevalence rate of known cases of diabetes showed a tendency to increase from 3.1% in 1975 to 5.1% in 1986. Prevalence rates adjusted for age and sex showed an increase in the mean prevalence for 1986 compared with that of 1981. The prevalence rate was significantly higher for the rural population for the age group 45-64 yr old and for the urban population for the age-group greater than or equal to 65 yr. The prevalence rate compares with that of Mexican Americans and Puerto Ricans in the New York City area. On the basis of the prevalence data, approximately 90% of the diabetic population is non-insulin dependent and 10% are insulin dependent. Major risk factors thought to explain the increased prevalence of non-insulin-dependent diabetes are increasing longevity of the Puerto Rican population, genetic predisposition, obesity, and changes in life-styles. In conclusion, Puerto Ricans, as other Hispanic Americans, have a higher prevalence of diabetes than the white American population. PMID- 1914819 TI - Pathogenesis of NIDDM in Pima Indians. AB - The Pima Indians of Arizona have the highest reported prevalence and incidence of non-insulin-dependent diabetes mellitus (NIDDM) of any population in the world. A cross-sectional and longitudinal study was begun in 1982 to determine the metabolic characteristic(s) that is (are) predictive of the development of NIDDM and to document the sequence of metabolic events that occur with the transition from normal to impaired glucose tolerance and then to diabetes. Preliminary analyses suggest that insulin resistance is a primary abnormality predisposing Pima Indians to develop impaired glucose tolerance, and that the development of diabetes occurs with subsequent pancreatic failure. PMID- 1914821 TI - Diabetes in pregnancy in Mexican Americans. AB - Diabetes in pregnant Mexican-American women is a serious and expensive health problem. At the University of California, San Diego Medical Center, 44% of pregnant women are Mexican American. In the Diabetes in Pregnancy Clinic, only 7% of women with insulin-dependent diabetes are in this ethnic group compared with 66% of non-insulin-dependent diabetic patients and 51% of those with gestational diabetes mellitus (GDM). GDM is the most common complication of pregnancy in Mexican Americans with a prevalence approximately three times higher than that of whites (4.5 vs. 1.5%). Mexican-American obese GDM subjects had more frequent cesarean sections and were more likely to have complications of premature rupture of membranes and preterm labor (NS). Polycythemia and sepsis also occurred more often in their infants. Anthropometric measurements in infants of both lean and obese GDM subjects differed from those of infants of mothers without GDM. Infants of lean mothers with GDM were heavier and longer than those of lean mothers without GDM. In addition, they had increased waist-hip ratio and triceps and subscapular skin folds. Infants of obese mothers with GDM were heavier than those of lean mothers with GDM. Moreover, they were longer (P less than 0.04); had a higher body mass index (P less than 0.04); and larger waist and hip circumferences (P less than 0.03) and buccal (P less than 0.01), subscapular (P less than 0.01), and sum of skin-fold measurements (P less than 0.03). Our observations indicate that pregnant diabetic Mexican-American women have predominantly GDM and non-insulin-dependent diabetes. They represent a major public health problem because of increased maternal and neonatal morbidity. PMID- 1914820 TI - Obesity in Hispanic Americans. AB - The prevalence of obesity among Hispanic American populations is generally greater than among white populations in the United States. Among Mexican Americans, the prevalence of obesity was higher than among either Cuban Americans or Puerto Ricans. It is well known that the prevalence of diabetes increases with increasing levels of obesity or body mass index. However, it does not appear that the high prevalence of obesity in Mexican Americans completely accounts for the higher prevalence of diabetes seen in this ethnic group. Among Mexican Americans, the association of selected cardiovascular disease risk factors, high-density lipoprotein cholesterol subfractions and systolic blood pressure, was similar to that seen among other U.S. populations. Individuals with diabetes had higher values than seen among those without diabetes. In a comparison of nutrient intake in two Mexican-American populations, one rural and one urban, there were no major differences other than higher calorie intakes in the rural population compared with the urban population. In addition, the diet in the rural population, based on higher levels of the Keys score, was more atherogenic than that of the urban population. PMID- 1914822 TI - [The new SOS chromotest (CEA test) for demonstrating mutagens and promutagens based on the indicator strain Salmonella typhimurium TA1535]. PMID- 1914823 TI - [Parallel complementary sequences in natural DNA: the parallel biosynthesis hypothesis]. PMID- 1914824 TI - [The covalent immobilization of cholinesterases in polyacrylamide hydrogels]. PMID- 1914825 TI - [The level of immunoglobulins in the blood serum of the Greenland seal]. PMID- 1914826 TI - [Dna-specific catalytic antibodies in human blood sera]. PMID- 1914827 TI - [Surface topography of glycoconjugates of the plasmalemma of developing neurons during disruption of cytoskeletal elements]. PMID- 1914828 TI - [Comparison of the amino acid sequence of structural proteins from attenuated and pathogenic strains of the Venezuelan equine encephalomyelitis virus]. PMID- 1914829 TI - [Synthesis of recombinant antibodies (mouse/human) in lymphoid and nonlymphoid cells]. PMID- 1914830 TI - [Cytokine-dependent regulation of the production of TNF alpha and active forms of oxygen by macrophages of intact mice and mice with B16 melanoma]. PMID- 1914831 TI - Introduction: new treatment prospects for osteo-arthrosis. PMID- 1914832 TI - Characterisation of the glycosaminoglycan component of matrix. AB - The glycosaminoglycan component (GAG-S) of Matrix was shown by electrophoretic and 13C NMR analyses to be a low-molecular weight chondroitin sulfate. NMR analysis also indicates that the internal composition of GAG-S is 72.5% chondroitin 6-sulfate and 27.5% chondroitin 4-sulfate, with a degree of polymerisation corresponding to about forty monosaccharide residues. PMID- 1914833 TI - Metabolic fate of partially depolymerized chondroitin sulfate administered to the rat. AB - Partially depolymerized chondroitin sulfate (dCS) was tritiated and given to rats. With both the intramuscular and oral routes of administration the main route of excretion is urine. More than 40% of the radioactivity is present in tissues 24 h after administration. After intramuscular injection, radioactivity plasma levels rapidly increase with a peak at 0.6 h. The separation of the radioactive material on a Biogel P-4 column shows that the radioactivity in the first hour after injection is mainly constituted of dCS with molecular weight higher than 4000 daltons (dCS greater than 4000). The composition of the radioactive material changes with time; after 24 h the dCS greater than 4000 is a few percent of the total radioactivity. A large amount of tritiated water due to exchange and metabolization of dCS is found. Mono-, oligo- and polysaccharides resulting from the breakdown of dCS are also present. After oral administration, plasma radioactivity rapidly increases, with a shoulder and a small peak after 1 h and a large peak after 11 h. A tropism of the radioactivity towards glycosaminoglycan-rich tissues is observed. The presence of dCS greater than 4000 in plasma, synovia and cartilage after oral and intramuscular administrations of dCS may explain the chondroprotective effect of exogenous dCS. In fact, desulfated and sulfated oligo- and polysaccharides have regulatory effects on the synthesis and breakdown of hyaluronate-proteoglycan complexes of cartilage. PMID- 1914834 TI - Chondroprotection with chondroitin sulfate. AB - The remarkable insights into the pathogenesis of osteo-arthrosis (OA) have also affected the therapeutic field. Efforts have been made to find drugs which would somehow block or slow down the evolution of this disease. In this connection, a major contribution has been made by the investigations on glycosaminoglycans (GAGs), which play a crucial role in the physiology of joint cartilage. It was thus suggested that proper supplementation with GAGs might enable chondrocytes to replace the proteoglycans (PG). Galactosaminoglucuronoglycan sulfate (GAGGS) has been used for this purpose. In preliminary clinical trials, GAGGS exhibited a remarkable tolerability and good therapeutic efficacy. GAGs are generally able to inhibit certain enzymes present in the synovial fluid which may damage joint cartilage (elastase, hyaluronidase). Moreover, GAGGS has also been shown to act as an anti-inflammatory drug since it has an inhibitory effect over the complement. All these data supply evidence that, in theory, GAGGS may have a chondroprotective effect in patients with OA. In addition to the positive results of preliminary clinical trials, the use of GAGGS in OA therapy is based on the fact that this drug is absorbed by the body, is concentrated in the cartilages and produces no toxic or teratogenic effects. In the clinical studies performed so far, although of the open type, GAGGS has always yielded clinical improvement both of painful symptoms and of limited function thanks to its proven anti inflammatory activity. Thus once the results from other ongoing trials (double blind) are available, hopefully GAGGS will in fact become a basic drug for OA therapy. PMID- 1914835 TI - Clinical efficacy and tolerance of galactosoaminoglucuronoglycan sulfate in the treatment of osteoarthritis. AB - An open design has been carried out by the authors comparing the efficacy and the tolerance of galactosoaminoglucuronoglycan sulfates (GAGs) with those of ibuprofen lysine in patients affected by osteoarthritis (OA). The experimental group included forty patients of both sexes, aged from 35 to 67 years, with diffuse OA. Ten patients were treated with GAGs administered orally (600-1200 mg/die) and ten patients with GAGs administered intramuscularly (50-100 mg/die); likewise for the ibuprofen therapy two subgroups were formed, such that ten patients were given the drug orally (1500-2500 mg/die) and ten patients had intramuscular therapy (400-800 mg/die). The treatment lasted 40 days. The parameters considered were: pain at rest, pain on pressure, pain on active movement and pain on passive movement. Tolerance was considered by carrying out some routinary laboratory tests and a careful clinical and anamnestic examination. At the end of the study, an improvement in all the clinical variables considered was found in both groups of patients, with no significant differences between the oral and the intramuscular administrations. With regard to tolerance, it must be noted that 10% of the patients in each of the two considered groups patients suffered from gastro-intestinal diseases (pain, nausea, pyrosis). The results achieved, therefore, confirm the efficacy and above all the good tolerance of GAGs in the treatment of OA, characteristics of particular importance for a drug designed for the therapy of a chronic pathology such as OA. PMID- 1914836 TI - Effects of the treatment with matrix on elderly people with chronic articular degeneration. AB - Clinical trials have been conducted to evaluate the effectiveness of Matrix in osteoarthritis, mainly as regards the advantages offered by its physiological mechanism of action. The experiment, lasting 6 months, was performed on two hundred patients in four different Hospital Departments and one University Center. The results showed a considerable improvement both in pain and in mobility. No relevant side effects were found; only 3% of patients, with oral administration, noticed slight nausea and found it necessary to interrupt treatment. PMID- 1914837 TI - Galactosaminoglycuronoglycan sulfate (matrix) in therapy of tibiofibular osteoarthritis of the knee. AB - To evaluate the efficacy and tolerance of galactosaminoglycuronoglycan sulfate (Matrix vials) in the therapy of tibiofibular arthritis of the knee, forty patients suffering from this illness at radiological stages 1 and 2 undergoing concomitant therapy with NSAIDS, were randomized into two groups of twenty. The treatment group received the drug under study and the control group received placebo. Treatment was carried out in double blind. The therapy protocol comprised 25 intramuscular injections (one injection twice a week). This cycle was repeated for 6 months, for a total of 50 injections. The patients were visited on days 0, 90, 180, 240, 330 and 360. At each visit the following symptoms were evaluated: spontaneous pain, pain on loading, on passive movement and on pressure; changes in NSAIDS posology were also recorded; lastly any possible side effects were noted. Analysis of results has shown a statistically significant higher therapeutic effect on treatment with Matrix for all the symptoms taken into consideration. No important side effects were noted, either local or systemic; in two cases only in the group treated with Matrix and in the same number in the control group slight dyspeptic symptoms were found to occur, but without requiring suspension or reduction in posology. Two patients in the Matrix group and one in the control group left the study for non-compliance with the type of administration. The good clinical results obtained, together with the excellent tolerance shown by the drug, suggest that Matrix may be the drug of choice in the "basic" therapy of osteoarthritis, with its efficacy being demonstrated in an increasing number of clinical studies. PMID- 1914838 TI - Sensitization studies on chondroitin sulfate. AB - Results of several tests in guinea pigs performed in order to check the hypersensitivity hazard of chondroitin sulfate are reported. As per theoretical expectations, no immuno-enhancing effect leading to hypersensitivity was recorded. PMID- 1914839 TI - Chondrocyte physiopathology and drug efficacy. AB - After a brief exposition on the physiopathology of cartilage, and characteristic features of chondrocytes and proteoglycans (PGs) in osteoarthritis (OA), it is underlined how different molecules of GAGs and aggregated PGs added to the culture media can prevent damage and reduction of GAGs and fibril production in chondrocytes cultured with NSAIDs and corticosteroids. In animal models of OA, the local or general administration of GAGPS reduces the proteinase activity, the level of uronic acid in synovial fluid and the number of inflammatory cells in synovia. In the Pond-Nuki dog, GAGPS improves the cartilage surface. These favourable events can also occur in human OA, where it is, moreover, difficult to monitor the patients. For this purpose, patients must be selected in the first two stages of primary OA, and followed using NMR, the only device able to scan cartilage and subchondral bone, to determine their consistency and thickness, and to provide information on water content. PMID- 1914840 TI - Experimental and clinical pharmacology of glycosaminoglycans (GAGs). AB - The experimental and clinical pharmacology of glycosaminoglycans (GAGs) is discussed, including that of heparin and related compounds, hyaluronic acid and chondroitin sulfates. PMID- 1914841 TI - A pharmacological approach to glycosaminoglycans. AB - A pharmacological approach to glycosaminoglycans (GAG) is presented, reviewing their synthesis, functions and in particular their mechanism as drugs. The application of GAG sulfates in osteoarthritis therapy is examined in detail. PMID- 1914842 TI - The effects of enflurane on the DNase I activity in an isolated enzyme preparation and in the DNase I-G actin complex. AB - The effects of enflurane on the DNase I activity in an isolated enzyme preparation and in the DNase I-G actin complex were investigated. DNase I, DNase I-G actin complexes and G actin were exposed to various (0.2-5.0 vol.%) enflurane concentrations for 180 min. Thereafter, DNase I activity was determined. Compared with controls, DNase I activity and the inhibitory capacity of G actin for DNase I were not affected by enflurane. However, there was a shift in the absorption maximum of DNase I after exposure to enflurane. The results suggest that enflurane alters the DNase I conformation without inhibition of DNase I function. In clinical subjects, side effects of anaesthesia can occur by interactions between hydrophobic anaesthetics and the hydrophobic groups of amino acids in proteins. PMID- 1914843 TI - In vitro studies with Bay V 3522, a new oral cephalosporin. AB - The in vitro activities of Bay v 3522, cefaclor, cephalexin, cefuroxime, cefixime, amoxicillin/clavulanate (2:1) and reference penicillins were compared against 314 clinical isolates of Gram-positive and Gram-negative bacteria and nine strains of Escherichia coli that differed in their outer membrane proteins in agar dilution tests with an inoculum of 10(4) cfu/spot. The beta-lactamase stabilities of the cephalosporins were also evaluated by spectrophotometric assay using 21 different beta-lactamases. Bay v 3522 was the most potent cephalosporin overall against Gram-positive pathogens, but slightly less active than amoxicillin/clavulanate. In addition to being highly active against streptococci (MIC90 = 0.25 micrograms/ml) and methicillin-susceptible staphylococci (MIC90 = 1.0 micrograms/ml), Bay v 3522 was markedly more active than the other cephalosporins against Enterococcus faecalis (MIC90 = 4 micrograms/ml). Bay v 3522 was less potent against Gram-negative pathogens, especially nosocomial isolates of Escherichia coli and Klebsiella pneumoniae (MIC90 greater than 64 micrograms/ml), but was active against Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and beta-lactamase-negative Neisseria gonorrhoeae (MIC90 = 1.0 micrograms/ml0. Hydrolysis of Bay v 3522 by most beta-lactamases examined was significantly less than that observed for cephalothin and cefaclor; similar to that observed with cephalexin; and less than that observed with cefixime and cefuroxime. None of the beta-lactamases examined hydrolysed Bay v 3522 at a rate greater than 20 nmol/min/mg. The in vitro potency of Bay v 3522 against Gram-positive and fastidious Gram-negative pathogens and its resistance to hydrolysis by beta-lactamases produced by them support further investigation of this cephalosporin as a new oral therapeutic agent. PMID- 1914844 TI - In vitro activity of flurithromycin against some genital pathogens. AB - The in vitro antibacterial activity of a new macrolide drug, flurithromycin, was evaluated in comparison with the activity of erythromycin A against some genital pathogens. The strains tested, C. trachomatis, U. urealyticum. M. hominis, N. gonorrhoeae, S. agalactiae and M. genitalium, were both clinically isolates and ATCC standards. The evidenced activity of flurithromycin is similar to that of erythromycin A. Resistances with both macrolides were found in all M. hominis strains and in one strain of U. urealyticum. No particular differences are exhibited between clinical and standard microorganisms. PMID- 1914845 TI - Some pharmacokinetic data on miocamycin II. Concentrations in gynaecological tissues. AB - The gynaecological tissue levels of miocamycin were studied in ten female patients after pre-operative administration. The patients were divided into two groups on the basis of the scheduled sampling time. All the patients received 4200 mg of the drug, divided in 7 tablets of 600 mg each every 8 h, last administration 2 or 3 h before surgery. The tissue levels, obtained by means of the microbiological method (Sarcina lutea 9341), were frequently higher than those obtained in the serum at the same time. Miocamycin reached the highest concentration in the endometrium (2.5 micrograms/g) and the lowest in the vagina (1.1-0.8 micrograms/g). PMID- 1914846 TI - Rheological activity of propionyl L-carnitine. AB - The authors have evaluated the efficacy of chronic administration of propionyl l carnitine versus Buflomedil chlorhydrate in patients affected by vasculopathies. Patients were divided into two groups, A (n = 14) and B (n = 7); a third group C (n =7) was a control group of normal subjects. Groups A and C received 500 mg tablets of propionyl l-carnitine orally t.i.d. for 20 days. Group B received 40 mg of Buflomedil chlorhydrate i.v., b.i.d. for the same treatment period. Several blood cell viscosity parameters were evaluated. At the end of the trial it was possible to detect in the propionyl l-carnitine treated group a statistically significant decrease in haematic filtration time (HFT) and an increase in red blood cell flow velocity (Vrbc). Furthermore, some important rheological properties were noted, as demonstrated by modifications in the whole blood filtration, red blood cell flow velocity and viscosity of platelet-rich plasma following the addition of ADP. PMID- 1914848 TI - [Current status and prospect of reperfusion therapy and PTCA in acute myocardial infarction in China]. PMID- 1914847 TI - Post-marketing survey of nimesulide in the short-term treatment of osteoarthritis. AB - A multicentric trial was carried out to assess the therapeutic efficacy and tolerability of nimesulide in the treatment of patients with osteoarthritis. The trial involved 1600 general practitioners, 80 orthopedists and 88 specialists in internal medicine. A total of 22,938 ambulatory patients was admitted to the trial. Patients were given nimesulide tablets (40%) or granules (60%) from 100 to 400 mg/day for a length of time ranging from 1 to 3 weeks. The treatment was effective in relieving spontaneous pain and morning stiffness. The level of patients with adverse reactions, presumably related to nimesulide and mostly involving the gastro-intestinal tract, was 8%. The results of this study suggest that nimesulide is effective and well tolerated in the short-term treatment of a large number of patients with osteoarthritis. PMID- 1914849 TI - [Seminar on interventional treatment and thrombolytic therapy in coronary and valvular diseases]. PMID- 1914850 TI - [Referential project for thrombolysis in acute myocardial infarction]. PMID- 1914851 TI - [Evaluation of clinical criteria of coronary artery recanalization in acute myocardial infarction]. AB - Clinical features of recanalization of infarct-related coronary artery during thrombolytic therapy or emergency PTCA and their correlation with immediate coronary angiography were analysed in 23 patients with acute myocardial infarction (AMI) to evaluate the predictive value of clinical criteria of reperfusion. The coronary angiography was performed before treatment and every 15 to 30 minutes during intravenous (rt-PA) or intracoronary (UK or SK) thrombolysis. Reperfusion was achieved in 16 cases by thrombolysis and in 4 cases by PTCA. The results revealed that in patients with reperfusion chest pain was relieved rapidly at least 70% in a period of 30 minutes, the ST segments fell by 50% or more from their elevated levels during a period of 30 minutes. Transient "paradoxical" increase of ST segment elevation followed by rapid falling was observed in 4 patients. This phenomenon was considered as a reliable marker of reperfusion. The changes in cardiac rhythm and conduction were noticed in 90% of the patients with reperfusion, among them accelerated idioventricular rhythm and disappearance of new-onset AVB and intraventricular conduction defects were useful bedside evidences of reperfusion, and transient significant sinus bradycardia or AVB with or without transient hypotension were useful markers of reperfusion in inferior myocardial infarction. When these clinical criteria were separately used as predictor of infarct-related coronary artery recanalization, the specificity was about 70% to 80%. Using the presence of all 3 criteria, the specificity and predictive value increased to 100% and the sensitivity was 70.6%. The time interval between onset of symptoms and peak CK and CK-MB were significantly shorter in patients with reperfusion than in those without persistent reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914852 TI - [A primary report on thrombolytic therapy of acute myocardial infarction in 40 cases]. AB - Forty cases with acute myocardial infarction were treated by thrombolysis from June, 1989 through September, 1990. 32 males and 8 females. Age 44-76 (60 +/- 7.1) years. Coronary angiography was performed in 19 patients 10 days after intravenous thrombolysis on average. With intravenous thrombolysis the reperfusion rates were 69.2% (9/13) for streptokinase and 53.8% (7/13) for urokinase (Green Cross Company, Japan) according to the clinical criteria. No reperfusion was observed in 8 cases treated by China-made urokinase. The reperfusion rate of intracoronary thrombolysis was 85.7% (6/7). 5 cases had hemorrhagic complications, skin ecchymosis in 2 and mild gastrointestinal bleeding in 3, and no transfusion was necessary. No intracranial hemorrhage was noticed. PMID- 1914853 TI - [Percutaneous transluminal coronary angioplasty. A report of 100 cases]. AB - Percutaneous transluminal coronary angioplasty (PTCA) was performed in 100 coronary heart patients with 122 vessels and 138 lesions dilated. Among these 100 cases, there were 39 complex PTCA performed. The primary success rate was 93% (93/100), was 94.3% (115/122) according to vessel dilated and was 92.1% (127/138) according to lesion dilated. In 4 cases whose lesions were located at the bifurcation of the vessel, kissing balloon technique via a single guiding catheter was applied with success. In 5 cases of total occlusion PTCA was performed with success in 4. PTCA with stent in 1. PTCA was performed in 1 cases of high risk whose LVEF was only 30% and coronary hemoperfusion pump was used during the procedure. Emergency PTCA was performed in 3 AMI patients during the acute phase and elective PTCA in 8 AMI cases after successful thrombolytic therapy. There were complications in 9 cases (9%). Among these 9 cases, 2 developed O-wave MI which recovered after medicinal therapy. One AMI complicated with heart failure was treated by emergency PTCA with success, but the patient died 10 days after PTCA due to pump failure and pulmonary infection. There were no deaths due to PTCA, nor was emergency coronary artery bypass graft (CABG) performed. These cases were followed for 1-30 months on an average of 13 months. Clinical success rate was 91.3%. The clinical success rate was 93.1% by 201Tl perfusion study. Restenosis in 7 cases was confirmed by coronary angiography. For these restenotic cases, PTCA was repeated with success in 4, CABG performed in 1, coronary atherectomy in 1, and medicinal therapy employed in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1914855 TI - [A preliminary report on percutaneous balloon valvuloplasty by domestic balloon catheter]. PMID- 1914854 TI - [Percutaneous mitral commissurotomy by a domestic balloon catheter in 215 patients and a follow-up study of 41 cases]. AB - Between June, 1987 and June 1990, percutaneous balloon catheter mitral commissurotomy (PBMC) was performed in 215 patients (mean age 37.1 +/- 10.1 years) with rheumatic mitral stenosis by domestic balloon catheter and were successful in 213 patients (99%). After PBMC, there was a significant improvement in mitral gradient (2.58 +/- 0.93 kPa to 0.66 +/- 0.31 kPa, P less than 0.001), mean left atrial pressure (3.18 +/- 0.94 kPa to 1.26 +/- 0.55 kPa, P less than 0.001), mitral valve area (1.14 +/- 0.22 cm2 to 2.27 +/- 0.42 cm2, P less than 0.001) and left atrial dimension (46 +/- 5 mm to 36 +/- 4 mm, P less than 0.001). Severe mitral regurgitation was noted in two patients (0.9%) and pericardial tamponade in one patient (0.5%). No death was occurred. 41 patients from the first 160 ones were followed up for a mean of 25 +/- 6 months (12-36 months). Mitral valve area remained stable in all but one with restenosis. In addition, the experience on prevention and cure for complications of PBMC were discussed. PMID- 1914856 TI - [An application of His bundle electrogram to locate fossa ovalis during percutaneous transseptal balloon valvuloplasty]. AB - A new technique to locate the point of atrial septal puncture, i.e. His bundle electrogram locating method (HBELM), was reported. By using this HBELM, the successful rate of atrial septal puncture was 100% in 21 cases of mitral stenosis during percutaneous transseptal balloon valvuloplasty and in 5 cases of them, the puncture needle got into left atrium smoothly through patent fossa ovalis at the position determined by HBELM without making puncture. As well known, the point of atrial septal puncture is fossa ovalis. According to the anatomy, His bundle is located at the same horizontal line as fossa ovalis. After HBE being recorded, a horizontal line is drawn from the point of His bundle catheter electrode. The authors suggest that the intersect of this line with right border of thoracic vertebra should be the point of atrial septal puncture. The above study showed that HBELM for atrial septal puncture is a correct and easy method and may be better than other methods used before. PMID- 1914857 TI - [Experimental and clinical studies of using Nd: YAG laser via domestic metal cap and sapphire tip delivery systems]. AB - Sixteen segments of normal human cadaver aorta were irradiated by Nd: YAG laser beam delivered via domestic metal cap and sapphire tip fiber systems. Results revealed that the adherence to target tissue and tissue damage were more apparent with metal caps than those with sapphire tips. Furthermore, the latter had smoother edges of ablation crater less carbonization layers and smaller thermal necrotic zones. The delivery systems were used to perform laser angioplasty in 2 iliac and 5 coronary atherosclerotic arteries and all achieved immediate recanalization. PMID- 1914858 TI - [A canine trial using transventricular laser channel]. AB - Revascularization of ischemic myocardium by Nd: YAG laser channels was studied in 33 dogs with myocardial infarction. The dogs were separated into epi- and endo cardial (percutaneous and intraoperative) groups. Laser channels with a diameter of 400 microns were made by 6.7-6.8 watt lasersonics Nd: YAG unit. Then the dogs were killed and core samples of myocardium from the laser area were taken as planned. Evaluation includes pre- and post-operative echocardiography and radionuclide scanning to measure left ventricular (LV) function and regional blood flow. Improved LV function and increased uptake of radionuclides were demonstrated. There was no operative mortality. The histologic evidences of reconstructed myocardial microcirculation and communications with myocardial channels by laser were also reported. PMID- 1914859 TI - [Serum mitochondrial aspartate aminotransferase (ASTm) in acute myocardial infarction]. AB - The increase of serum ASTm activity might reflect the severity of damage at the subcellular level of the myocardium. 50 patients with acute myocardial infarction (AMI) were observed. The mean peak ASTm activity was 34.34 +/- 34.60 IU/L and 48 patients (96%) greater than or equal to 9 IU/L (two times median value of normal subject). The peak time (36 h) came later and the duration (120 h) was longer than that of CK-MB. ASTm/ASTt ratio in groups of AMI, non-AMI heart failure and acute ictero-hepatitis was 0.25 +/- 0.10, 0.02 +/- 0.05 and 0.05 +/- 0.02 respectively. The former was significantly greater than other two groups (P less than 0.01). The activity of ASTm in AMI cases with heart function at I, II and III + IV (Killip classification) was 21.8, 40.2 and 76.2 IU/L respectively (F = 8.407 P less than 0.01) and it was 84.9 and 24.7 IU/L in the death and surviving groups (P less than 0.01). The result showed that the estimation of serum ASTm level was helpful to the establishment of diagnosis in the patients with AMI who were sent delayed to the hospital. It held special significance in evaluating the severity of myocardial damage, heart function and in predicting the prognosis of AMI. PMID- 1914860 TI - [The relation between coronary diseases and lipid peroxidation]. PMID- 1914861 TI - [A clinical observation in 17 cases of electric alterans in patients with unstable angina with ST elevation]. PMID- 1914862 TI - [Electrophysiologic characteristics of multiple atrioventricular accessory pathways in patients with pre-excitation syndrome]. AB - The electrophysiologic studies in 4 patients with multiple accessory pathways (AP) were reported. The results showed that in these patients, the electrophysiologic characteristics were diversified: The VA intervals often changed abruptly during ventricular pacing at a set rate; and during ventricular pacing with incremental rate or a single premature stimulus scanning, the VA intervals revealed several different constant values. At the onset of AV reentrant SVT with wide QRS complex, the HBE showed VA-VA sequence and no H wave could be found; when orthodromic reentrant SVT, the VA interval and SVT cycle length were various, especially at the beginning of the onset. It was found that when the multiple APs located at both the right and left side and the septum of the heart, the variation of the VA interval would follow the variation of the atrial excitation sequence; when the multiple APs located at the same side of the heart, the atrial excitation sequence was unchanged. Of the 4 cases, 3 received epicardial mapping and surgical treatment. All the existence and locations of the APs suggested by the electrophysiologic studies were confirmed during the operation except one AP in which the location was slightly deviated from the pre estimation. PMID- 1914863 TI - [A matched study on major risk factors in myocardial infarctions]. PMID- 1914864 TI - [Risk factors and trend of changes in hypertension and coronary heart disease in Daqing]. PMID- 1914865 TI - [Antihypertensive activity of monoclonal antibody to angiotensin II]. AB - The antihypertensive effect of monoclonal antibody to angiotensin II (MAAII) was studied in renovascular hypertensive (RVH) rats. We found that MAAII could antagonize the pressor effect of exogenous angiotensin II but not of vasopressin in vivo. Five minutes after the administration of MAAII (15 mg/kg, i.v.), plasma angiotensin II could not be detected by radioimmunoassay and the mean blood pressure (MBP) decreased in RVH rats more than in normotensive rats (delta MBP: 5.33 +/- 0.12 and -1.17 +/- 0.29 kPa, respectively, P less than 0.01). The hypotensive effect of captopril was markedly inhibited by prior administration of MAAII, while that of nitroprusside and phentolamine was not. The results suggest that the antihypertensive effect of MAAII is mainly due to its specific binding to circulating angiotensin II. PMID- 1914866 TI - [The clinical aspect of percutaneous transluminal coronary angioplasty]. PMID- 1914867 TI - Acipimox--a nicotinic acid analogue for hyperlipidaemia. PMID- 1914868 TI - Oxpentifylline for venous leg ulcers. PMID- 1914869 TI - Update on MMR vaccination. PMID- 1914870 TI - Surgery for short sight? PMID- 1914871 TI - Rectal topical corticosteroid preparations. PMID- 1914872 TI - Alcohol problems in the general hospital. AB - Patients with acute alcohol-related problems are commonly encountered in hospital. All hospital doctors, as well as GPs, should be looking out for them to prevent or anticipate complications. Alcohol withdrawal ranges from an insignificant upset to a life-threatening syndrome with delirium, fits and serious neurological complications. Strong vitamins B and C injection deserves routine use in those at risk and is essential to treat such complications of withdrawal. Chlordiazepoxide is commonly used to attenuate the withdrawal syndrome; chlormethiazole is an alternative drug, for use only in hospital. After discharge from hospital a coordinated and integrated approach to management by the GP is essential: continued care and effective follow up are vital. PMID- 1914873 TI - Cooling the feverish child. PMID- 1914874 TI - [Lymphedema. Directions for proper actions and nursing measures in latent and clinically manifest lymphedema]. PMID- 1914875 TI - [The Feldenkrais method in ambulatory geriatric nursing and nursing of the sick]. PMID- 1914876 TI - [The community health nurse as a generalist]. PMID- 1914877 TI - [Bodily hygiene newly discovered. Change of consciousness in nursing]. PMID- 1914878 TI - [Qualifying organization of work. A strategy for the continuing education in ambulatory care]. PMID- 1914879 TI - [Family caring for family. Experiences with a discussion circle for nursing family members]. PMID- 1914880 TI - [Networking of home care services and a social work]. PMID- 1914882 TI - [Experiences in the organization of social work in the new federal districts. "...we could use you here very urgently"]. PMID- 1914883 TI - [Heirs, insurances and clients. Interest in the insurance of the nursing risk]. PMID- 1914881 TI - [Experiences in the organization of social work in the new federal districts. The principle of "attempt and error"]. PMID- 1914884 TI - [Oncologic nursing outside the hospital. Report of experiences of 4 years of ambulatory care of cancer patients in Basle]. PMID- 1914886 TI - [Examination scare]. PMID- 1914887 TI - [The new care and lodging legislation]. PMID- 1914885 TI - [Operating in the home. Ambulatory care by a visiting nurse from a pediatric cancer ward]. PMID- 1914888 TI - [Emphasis in the clinical specialization in nursing. New developments at the Louvain Catholic University in Belgium]. PMID- 1914889 TI - [What many elderly think about today--thoughts of a "young aged" on voluntary service by the elderly]. PMID- 1914890 TI - [Homelessness of single women. Karin N. from West Berlin as an example]. PMID- 1914891 TI - [Historical development and current state of regional anesthesia]. PMID- 1914892 TI - [Nursing requirements in the preparation for and the execution of regional anesthesia]. PMID- 1914893 TI - [Monitoring of patients with regional anesthesia]. PMID- 1914894 TI - [Qualifications for nurses in a pain clinic]. PMID- 1914896 TI - [Peridural anesthesia]. PMID- 1914897 TI - [Combination anesthesia]. PMID- 1914895 TI - [Spinal anesthesia]. PMID- 1914898 TI - [Brachial plexus blockade]. PMID- 1914899 TI - [Possibilities and limits in the use of regional anesthesia in children]. PMID- 1914900 TI - [Dealing with authority (authorities)]. PMID- 1914901 TI - [Thoughts on the participation of national socialist nursing personnel in euthanasia activities]. PMID- 1914902 TI - ["More continuing education" against frustration. First attempt at concretizing]. PMID- 1914903 TI - [A Czech-German school partnership between the vocational nursing school of the district Freyung-Grafenau and the Stredny zdravodnicka scola Pisek]. PMID- 1914905 TI - [Position of the educational concept: nursing professions]. PMID- 1914904 TI - [Educational concept: nursing professions]. PMID- 1914906 TI - [Fees for nursing administrators]. PMID- 1914908 TI - [Quality requirement of continuing education in the nursing professions]. PMID- 1914907 TI - [Position paper on the integration of nursing science, nursing pedagogy and nursing management into the scope of the university by the Permanent Conference of the higher educational institutions for administrators and teaching nurses in the German Federal Republic]. PMID- 1914910 TI - [Malignant peritoneal mesothelioma with unusual and extensive metastasis]. AB - A 43-year-old alcohol-dependent man had sustained three acute episodes of chronic pancreatitis. At the third hospital admission enlarged axillary and supraclavicular lymph nodes, widening of the mediastinum and bone metastases were noted. Cytological examination of a needle biopsy of the supraclavicular lymph node revealed a poorly differentiated adenocarcinoma. Because of the marked enlargement of the pancreas and the history, a rapidly and unusually metastasizing carcinoma of the pancreas was diagnosed. In view of the rapid deterioration of the patient no chemotherapy was begun and he died 4 weeks after admission. Autopsy confirmed the chronic pancreatitis but no carcinoma of the pancreas. Instead there was a peritoneal mesothelioma with extensive lymphogenous and haematogenous metastases. The incidence of this tumour is ever increasing. It should be included in the differential diagnosis, because survival time can be increased if the correct diagnosis is made very early. PMID- 1914909 TI - [20 years of selective coronary angiography (1968-1987). The indications, results and therapeutic consequences]. AB - 10,975 diagnostic left-heart catheterizations, performed between 1968 and 1987 in 8,436 men and 2,539 women, were analysed regarding indication, results and therapeutic implications. 6,974 patients (64%) had coronary heart disease, 2,573 (23%) a valvar defect and 849 a cardiomyopathy. The proportion of patients with coronary heart disease increased from 21% to 74% during the 20-year period, while that of patient with valvar defects fell from 52% to under 19%. Severe cardiac complications in relation to the procedure occurred in 0.88%, ending fatally in 8 patients (0.07%). 61% of patients with coronary heart disease and 31% of those with valvar defects were treated conservatively. Percutaneous transluminal coronary angioplasty (PTCA) gradually became more common after its introduction in 1977. In 1987, PTCA was indicated as often as a bypass operation. PMID- 1914911 TI - [Therapy-refractory primary intestinal lymphangiectasis]. AB - A 20-year-old man with severe physical weakness (from which he soon recovered spontaneously) was found to have hypoproteinaemia and lymphocytopenia (768/microliters). Ten years later, after having been free of symptoms in the meantime, oedema, ascites and abdominal pain occurred, associated with loss of physical capacity. Enteric loss of protein (alpha 1-antitrypsin clearance increased about thirtyfold) with a total serum protein concentration of only 3.7 g/dl, as well as histological evidence of lymphangiectasia of the small and large intestines provided the diagnosis of primary intestinal lymphangiectasia. In the course of the disease cholelithiasis and (after treatment with tranexamic acid) thrombosis of the axillary vein occurred. No treatment has been of any avail and the patient has been unable to work for three years. PMID- 1914912 TI - [The diagnosis of heparin-associated thrombocytopenia]. PMID- 1914914 TI - [The ileum pouch: indications, technics and long-term results]. PMID- 1914913 TI - [The therapy of heparin-associated thrombocytopenia]. PMID- 1914915 TI - [The adder]. PMID- 1914916 TI - [Edema in anorexia nervosa]. PMID- 1914917 TI - [The "anticardiolipin syndrome" in left-ventricular thrombus]. PMID- 1914918 TI - [The extracorporeal elimination of LDL cholesterol]. PMID- 1914919 TI - [The results of resuscitations in an emergency service]. AB - In a prospective study 166 consecutive cases of prehospital resuscitation by emergency doctors were analysed to ascertain those factors which affect the ultimate outcome. Cardiac causes were most frequent (69%): primary ventricular fibrillation was the most common ECG diagnosis (47%). Average time from definite cardiorespiratory arrest until onset of resuscitation procedures by an emergency doctor was 8.2 minutes, to first measures by other resuscitation personnel it was 6.6 minutes. In all cases in which resuscitation procedures were undertaken (in 33 within 10 minutes) this was done by medical personnel who were nearby by chance. 47 patients (28.3%) could be resuscitated and taken to hospital; 16 of them (9.6%) were discharged after "finally successful resuscitation", 13 without any neurological deficit. Favourable factors were: primary ventricular fibrillation and start of resuscitation manoeuvres within 10 minutes. These results highlight the need for training first-aid personnel so that the number of successful resuscitations can be increased. PMID- 1914921 TI - [Orthostatic tremor]. AB - Two men, aged 57 and 77 years old, reported increasing unsteadiness on standing upright for the past 2 and 5 years, respectively. It had become impossible for them to remain standing for more than 10 seconds, as otherwise they might fall down. Walking, sitting and lying were possible without difficulty. Both patients were found to have a fine tremor in both legs on standing only. There were no other neurological signs or symptoms. Electromyography of the leg muscles demonstrated tremor activity at 14-16 Hz. Propranolol, 40 mg three times daily, in the 57-year-old patient brought no improvement. However, on taking primidone, in slowly increasing doses up to 250 and 500 mg daily, respectively, the condition lastingly improved in both patients. PMID- 1914920 TI - [Metastasizing round-cell sarcoma of the right atrium]. AB - The chest roentgenogram in a 46-year-old woman with dyspnoea for several months revealed global cardiac enlargement. Echocardiography demonstrated a tumour in the right atrium, about 4 x 5 cm, as well as circular pericardial effusion. Septic temperatures occurred in the further course, and blood cultures grew Staphylococcus aureus. Recurrent pulmonary emboli and cerebral emboli with hemiparesis, especially of the brachiofacial region, occurred despite heparinization. Shortly after hospitalization a chest roentgenogram revealed a round shadow, about 1 cm in diameter, in the left upper lobe. The patient died in cardiogenic shock on the 16th hospital day. Autopsy showed the tumour to be a poorly differentiated round-cell sarcoma, originating from the wall of the right atrium, infiltrating the myocardium through to the epicardium and extending to the tricuspid orifice. The foramen ovale was open, making paradoxical emboli at atrial level possible. PMID- 1914922 TI - [Subacute chloroquine overdosage]. AB - Owing to a misunderstanding a 26-year-old man took for malaria prevention 2 tablets (1.0 g) chloroquine daily instead of the recommended dose of two tablets weekly. After 2 weeks he developed vertigo, generalized weakness and, after sun bathing, severe bullous light reaction. After 4 weeks generalized hair depigmentation occurred. Two weeks later abnormal accommodation and double vision set in so that he lost distant and near vision. All these signs disappeared after the drug was discontinued (vertigo, weakness and abnormal accommodation within 2 weeks; hair regrew in normal colour after 8 weeks). This case shows the whole spectrum of subacute chloroquine overdosage. PMID- 1914923 TI - ["Sludge" in the gallbladder--a critical diagnostic finding]. PMID- 1914924 TI - [Brain death diagnosis]. PMID- 1914925 TI - [Pseudo-obstruction of the colon]. PMID- 1914926 TI - [The fulminant toxic course of ulcerative colitis without the demonstration of megacolon]. PMID- 1914927 TI - [Percutaneous endoscopic gastrostomy]. PMID- 1914928 TI - [Tuberculosis of the larynx, oral cavity and pharynx]. PMID- 1914929 TI - [Nitroglycerin absorption by infusion tubes]. PMID- 1914930 TI - [Weight increase following nicotine abstinence]. PMID- 1914931 TI - [Lysis of gallstones with methyl tert-butyl ether: percutaneous transhepatic or transpapillary?]. AB - Thirty patients (23 women, 7 men, mean age 53 [24-77] years) with symptomatic radiolucent gallbladder stones were treated by litholysis with methyl tert-butyl ether (MTBE), introduced through a catheter inserted into the gallbladder either by the percutaneous-transhepatic route (n = 19) or the transpapillary route (n = 11). Correct placing of the catheter was more frequently successful by the percutaneous-transhepatic route than the transpapillary one (90 vs 73%). The duration of lysis (median: 7 h and 8 h, respectively) and the proportion of stones which were completely dissolved immediately after lysis (53 vs 55%) were similar in both groups. Supplemented by subsequent oral therapy, the success rate at 6 months was higher in the percutaneous-transhepatic group (83 vs 64%), however, recurrences were more frequent. In the percutaneous-transhepatic group there was one case of gall-bladder leak and one catheter dislocation, and in the transpapillary group there was one case of pancreatitis, one of induction of ether anaesthesia and one pulmonary embolism. MTBE lysis is a relatively speedy and effective mode of non-operative therapy for gall-bladder stones. The percutaneous-transhepatic method is suitable for younger patients with a normal gall-bladder. The transpapillary procedure is preferable for older patients, and also when gall-bladder puncture proves difficult or when there is concurrent choledocholithiasis. PMID- 1914932 TI - [Does the care of diabetic patients with renal failure in the predialysis phase need improvement?]. AB - The cardiovascular risk profile was assessed in all 208 diabetics accepted for dialysis in 28 German dialysis centres from 1985-1987 (104 men, 104 women, mean age 60 [22-82] years). 71 patients had type 1 and 128 type 2 diabetes, and 9 maturity onset diabetes of the young. Of 169 patients, 164 (97%) had hypertension (median systolic blood pressure at start of dialysis 200 [120-280] mm Hg). Only 74 patients (44%) were on continuing anti-hypertensive medication. Median serum cholesterol was 225 (66-424) mg/dl, LDL-cholesterol 158 (43-335) mg/dl and HDL cholesterol 32 (10-67) mg/dl. In patients with a history of myocardial infarction (n = 26) the median cholesterol concentration was 269 (126-424) mg/dl, while in those with no history of myocardial infarction (n = 132) it was 221 (66-280) mg/dl (P less than 0.05). Only 5% of the patients had received lipid lowering therapy. Out of 175 patients, 65 (37%) had a history of smoking, and 25 (14%) were still smokers at the start of dialysis. There was a strong association between smoking history and amputations. Only 98 of 208 patients (47%) had had a specialist ophthalmological examination in the 12 months preceding the start of dialysis. Proliferative retinopathy was present in 33 out of 53 (62%) type 1 and 15 out of 98 (15%) type 2 diabetics. Out of 22 patients with unilateral or bilateral blindness, 2 (10%) had received no photocoagulation. - This investigation reveals a need for better medical care of diabetics with pre-end stage renal failure. PMID- 1914933 TI - [Transitory AV block as a cardiac manifestation of Lyme disease]. AB - After one day of dizziness a 28-year-old man experienced a syncope on getting up. ECG revealed a 3 degrees atrioventricular (AV) block unresponsive to drug treatment. A temporary pacemaker was implanted. Erythema migrans 4 weeks before admission suggested Lyme carditis, and the diagnosis was confirmed serologically (ELISA increased polyvalently, IgM antibody titre 1:64, IgG antibody titre 1:512). On antibiotic treatment with amoxicillin (1 g three times daily) and prednisolone (initially 80 mg daily, with gradual dose reduction) the sinuatrial block regressed within 10 days. Holter monitoring still demonstrated occasional sinoatrial conduction disturbances for some days, until sinus rhythm was permanently re-established. This case illustrates that transitory AV block can be the sole manifestation of sporadic Lyme disease in Europe and should therefore be included in the differential diagnosis of any acute cardiac disease. PMID- 1914934 TI - [Multiple cerebrovascular lesions as fatal late sequelae of syphilis]. AB - A previously healthy man, aged 33 years, suddenly developed a hemiparesis and right facial paresis, as well as anisocoria and motor aphasia, preceded by recurrent attacks of dizziness. On admission he was somnolent. A flow murmur was heard over both carotid arteries; the blood pressure was 160/80 mm Hg. Cerebral computed tomography demonstrated multiple hypodense areas in the area supplied by several cerebral arteries, and marked cerebral oedema. Angiography of the aortic arch and the supra-aortic branches showed an occlusion of the left common carotid artery and a stenosis of the brachiocephalic trunk. The cerebral oedema, caused by ischaemia, did not respond to treatment. The patient died on the fourth hospital day from brainstem "strangulation". At autopsy syphilitic mesaortitis with characteristic lymphoplasmacellular endangiitis of the vasa vasorum of the aortic arch was demonstrated as the cause of the "aortic arch syndrome". Serology confirmed the diagnosis of an untreated tertiary syphilis. (VDRL titre 1:256; TPHA reactive; IgM-SPHA titre 1:64). Although a very rare cause, a late stage of syphilis should be considered in the differential diagnosis of cerebrovascular lesions in youngish patients. PMID- 1914935 TI - [Heart involvement in functional disorders of the thyroid gland]. PMID- 1914936 TI - [Opening and sending of mail in medical establishments]. PMID- 1914937 TI - [Prevention of thrombosis in symptomatic thrombocytosis?]. PMID- 1914938 TI - [Transferrin and ferritin in disordered iron metabolism]. PMID- 1914939 TI - [Preclinical lysis in acute myocardial infarct]. PMID- 1914940 TI - [Aimed endoscopic gastric lavage after propafenone overdose]. PMID- 1914941 TI - [Structure of the domestic animal stock in the old jurisdictions of the Federal Republic of Germany]. AB - After a short review of the size structure and the regional distribution of livestock holdings with cattle, pigs and poultry, the significance and distribution of those livestock holdings are presented, which according to their size and their density are excluded from certain national income compensations to German farmers because they are classified as not belonging to the farm sector proper by agricultural policy authorities. Compared to neighbouring member countries of the EC, the significance of these livestock holdings seems rather small. The introduction of the milk quota regime and the exclusion of larger livestock holdings from certain income compensations have retarded the process of structural change in livestock keeping since the middle of the 1980s. Among factors influencing the future development of the structure of livestock holdings, scientific and technical innovations in livestock breeding and husbandry as well as developments in the distribution of food will prevailingly intensify the tendencies of continuing concentration processes in livestock holdings whereas environmental legislation and agricultural price and market policies will probably counteract these tendencies. PMID- 1914942 TI - [Structure of the domestic animal stock in the new jurisdictions of the Federal Republic of Germany]. AB - Results of investigations about the pattern of livestock in the five new countries of the Federal Republic are described in this paper. Groupings about the distribution of enterprises with cattle-, pig- and sheep-keeping and their animals to classes of size set priorities. The problem of mass-animal keeping is shown in a survey about large equipment. Calculations of manure units per hectare agricultural area show, that with the maintaining of necessary organisation principles the permissible yield guidelines of manure and liquid manure should not be exceeded. PMID- 1914943 TI - [Noise emissions from animal farms. Causes, effects, measures to reduce them]. AB - Noise output of animal farms may have different reasons and effects and must be judged generally in dependence of the local conditions. It can be influenced by means of organization, technics and construction. Financial compensation in both directions is known in order to preserve good terms with the neighbours. PMID- 1914944 TI - [Emissions of dust and microbes from animal housing]. AB - The content of airborne dust and germs in animal houses is described qualitatively and quantitatively. After having left the animal house by way of the exhaust air the microorganisms suffer a decay which is caused by dispersion and death-rate. The dispersion can be demonstrated by models. The boundary of the dispersion of germs and dust is about 200 m from source under normal conditions. Epidemiologic studies indicate that some virus particles can be transported over several miles by way of the air. Control of airborne dust and germ levels in animal houses is still poor. PMID- 1914945 TI - [Odor and ammonia release during and after application of livestock manure]. AB - Slurry application causes often heavy odour and ammonia emissions. Those emissions are influenced by weather conditions, kind and dry matter content of slurry, soil conditions, plant growth and kind of slurry application and incorporation into the soil. On arable land odour and ammonia emissions can be kept low by soon incorporation into the soil and after top dressings on cropped fields by early application (end of January, February, at favourable weather conditions). For grassland, emissions can be reduced by applying slurry at favourable weather conditions, by slurry dilution with water or by "washing". Slurry injection methods or slurry acidification are still problematical. PMID- 1914946 TI - [Livestock manure as a vector for infectious agents]. AB - The causative agents of nearly all bacterial and viral infectious diseases are either directly excreted by the infected animals or they reach the floor via other ways and thus end-up also in the fecal and urinary excretions of the animals. Occasionally pathogens also can be found in slurries of clinically unsuspected livestock for a short period of time while they pass through the gut of individual animals without colonization or invasion of the tissues (e.g. salmonellas). Consequently the manures are a potential for spreading infectious diseases. But their real significance as a vector for infectious agents is to a large extent still unsolved, because in the literature only very few and sometimes doubtful cases are described. During storage of manures the numbers of pathogens are reduced. This effect can be intensified by prolongation of the storage time. To assess the real epidemiological significance of the animal manures as vectors for infectious diseases further research work is urgently needed. After disinfection of animal manures in accordance with the regulations during eradication of notifiable diseases no cases of spread of disease became known in the Federal Republic of Germany. The problems of agricultural utilization of manures in water protection areas are discussed from a microbiological point of view. PMID- 1914948 TI - [Effect of livestock manure on the chemical quality of groundwater]. AB - In Germany groundwater represents the main source for the water supply. Up to the present the nitrogen surplus due to agricultural production has increased to about 100 kg N/ha and year. This surplus reaches other, mainly aquatic ecosystems, transported by water and trough the air. The impact of the long-term load through nutrients on groundwater is exemplified here in the case of Lower Saxony. In karst and rock aquifers the transport velocities are usually relatively high. After nutrients have left the root zone of the soil there remains in this kind of aquifer little opportunity for nitrate decomposition. Therefore rising nitrate values can soon be observed in pumpage wells. Intensive cattle production is especially widespread in the northern parts of Lower Saxony. In these areas of sandy aquifers the period of substance transport between the input into the system and reaching pumpage wells may cover years or even decades. Therefore there is a greater chance for nitrate decomposition. Nonetheless many upper aquifers are severely contaminated with nitrates, for instance. In many cases a reductive chemical environment can be observed, which causes an increase in substances such as iron or trace elements like nickel. This leads to considerable problems for water supply and treatment. In order to protect the quality and decomposition capacity of the groundwater for the next generation it is urgently necessary to minimise nutrient surpluses in the field of agricultural production. PMID- 1914947 TI - [Livestock manure as a vector for parasites--a report of experiences]. AB - Analysing the results of own investigations and informations in literature a review is given about the role of manure specially in stables of high-intensity cattle and pig production as a vector for exogenic parasite stages. In the course of investigations--in most cases simulating practice conditions--so-called indicator germs were used as test material. In cattle stables manure is significant as a vector for Eimeria species, Cryptosporidium parvum, Sarcocystis species, Taenia saginata and Fasciola hepatica. In pig stables manure must be classified as a reservoir of infections with Toxoplasma gondii, Sarcocystis species and Ascaris suum; moreover it represents a favourable culturing medium for stable flies. Possibilities to overcome the problems are discussed under parasitological field of view. PMID- 1914949 TI - [An unusual case of chronic fibrosing endometritis and mucometra in a Watusi cow (Bos primigenius f. taurus) with uterine foreign bodies]. AB - Genital organs, ureter, urinary bladder, and blood were collected from a 12 year old watusi cow which never exhibited estrous behaviour. Post-mortem findings and hormone assays, however, indicated the incidence of recent estrous cycles. The animal showed a chronic panmetritis, retained fetal membranes or fetal residues, an infected mucometra with cystic glandular hyperplasia, and a leiomyoma. Tubular genitalia, ureter, and urinary bladder exhibited subacute inflammation. PMID- 1914950 TI - [LDH and CK isoenzyme patterns in the blood plasma of horses with elevated CK, LDH and AST activities]. AB - The distribution of LDH and CK isoenzymes in blood plasma of ten clinically sound Thoroughbreds with reasonable performance and without elevated clinico-chemical blood variables (reference group) was compared with 57 Thoroughbreds, which had histories of mild locomotor disturbances and/or poor performance and had elevated CK, LDH and/or AST activities (trial group). The trial group was subdivided according to the number of altered blood variables and in the groups with two as well as three altered blood variables also according to the extent of alteration of the total CK activity. The pattern of LDH and CK isoenzyme distribution in the blood plasma of the reference group was the following: 22% LDH1, 36% LDH2, 34% LDH3, 6% LDH4 and 2% LDH5 as well as 75% CK1 and 15% CK2. The remaining 10% of the plasma electropherogram could not be alloted to any one of the two CK bands. All trial groups built showed a similar pattern of changes in their isoenzyme distribution independent on kind and combination of altered enzyme activities. The shares of CK1, LDH4 and LDH5 were significantly increased whilst the shares of CK2, LDH1 and LDH2 decreased. A multiple analysis of variance demonstrated that only increased total CK activities had a pronounced effect on distribution of LDH and CK isoenzyme patterns in the trial group (p less than 0.01 for LDH2, LDH3, LDH4, CK1 and p less than 0.05 for CK2). The conclusion of the study was that the altered distribution pattern of LDH and CK isoenzymes of the trial group signalized an increased skeletal muscle membrane leakage. PMID- 1914951 TI - Human immunodeficiency virus: transmission concerns in clinical practice. PMID- 1914952 TI - Idiopathic subjective tinnitus treated by biofeedback, acupuncture and drug therapy. AB - The effect of three treatment modalities of idiopathic-subjective tinnitus (IST): acupuncture (AP), biofeedback (BF) and Cinnarizine (Cin), was investigated in 58 randomly selected subjects. The findings show that at the end of treatment, 50% of the patients in the biofeedback group reported some amelioration in the level of the tinnitus, while 30% of the acupuncture group and only 10% of the group receiving Cinnarizine reported an amelioration of the tinnitus. Treatment by biofeedback caused a significant easing in the degree of discomfort caused by the tinnitus to patients during rest. Within the limitations of the sample study, our results indicate that the biofeedback method is more effective in comparison with acupuncture and Cinnarizine in the treatment of those suffering from tinnitus. PMID- 1914953 TI - Pitfalls in the diagnosis of CPA tumors. PMID- 1914954 TI - Middle ear disease in childhood achondroplasia. PMID- 1914955 TI - Custom made tracheostomy tubes. PMID- 1914956 TI - The temporoparietal fascia flap in head and neck reconstruction. AB - The temporoparietal-galeal system of flaps provides the head and neck surgeon with a reliable source of pliable, well vascularized local tissue capable of reconstructing auricular, oropharyngeal/base of tongue/lateral floor of mouth, dural, mandibular, and facial defects. This report provides a description of the types of flaps available, methods of dissection, and examples of reconstructive uses with this versatile tissue. PMID- 1914958 TI - Surgical approach to lipoma in the cheek. PMID- 1914959 TI - Hemostatis in laryngoscopy. PMID- 1914957 TI - Spontaneous perforation of the pharynx/esophagus. AB - Spontaneous perforation of the pharynx/esophagus is an unusual and probably under diagnosed condition. This small series of patients demonstrating consistent clinical and radiological evidence of this condition suggests that it may be more common than has previously been supposed. It appears that in the majority of cases where the site of rupture occurs in the pharynx or upper esophagus that a self resolving clinical picture normally occurs. PMID- 1914960 TI - Canine fossa puncture: an alternative to antro-nasal puncture of the maxillary sinus. PMID- 1914962 TI - Cosmetic rhinoplasty using the external approach. AB - Although the external rhinoplasty remains controversial it is difficult to understand why. The columella scar is of little significance since this becomes nearly invisible if the closure is carefully performed. There is a relative postoperative prolongation of nasal tip swelling in comparison with the closed technique, however this also becomes negligible with time. On the other hand, in our experience the open approach will achieve better understanding of the patient's individual anatomy and thus lead to a more predictable result through increased exposure and precision tailoring. The external technique facilitates the application of the great variety of tip refinements that have been developed over the years to allow facial plastic surgeons to get consistently excellent results in rhinoplasty. PMID- 1914961 TI - Applied nasal anatomy & embryology. AB - The embryology & anatomy of the nose as it is applied to rhinoplasty is surveyed so that the surgeon in training can develop a basis from which to review the literature. This review demonstrates the need for the consolidation and clarification of the nomenclature associated with the complex anatomy of the nasal pyramid. PMID- 1914963 TI - External rhinoplasty approach to unusual rhinologic procedures. AB - The technique of external rhinoplasty has enjoyed a renaissance over the last ten years primarily for cosmetic and functional septorhinoplasty. The versatility of this approach for a variety of rhinologic problems is exemplified by the previous case studies. More specifically, it affords unparalleled exposure of the nasal architecture and for the repair of septal perforations and nasal obstruction secondary to nasal valve deficiency. It may also aid the surgeon in defining the level of cartilage and skin thickness in the excision of rhinophyma. Beyond the unchallenged advantage of improved exposure that the external rhinoplasty approach affords, the surgeon is able to use both hands (as one is not occupied with the nasal speculum) and to view the procedure with binocular vision and greater depth perception. The teaching advantages are obvious. The method is not difficult, it may be done under local anesthesia and it entails no additional risk to the patient. PMID- 1914964 TI - External rhinoplasty approach to transsphenoidal hypophysectomy. AB - The external rhinoplasty approach is a modification of the well recognized transseptal transsphenoidal hypophysectomy technique first introduced by Cushing in 1910. Our approach has been used successfully in 75 cases over a six year period, demonstrating its efficacy and safety. It provides a simple, reliable, rapid technique for exposing the septum and the floor of the nose with excellent exposure to the sphenoid sinus and pituitary gland. There has been no loss of nasal tip projection or other cosmetic deformity. PMID- 1914965 TI - External rhinoplasty approach for nasal dermoids in children. AB - Nasal dermoid is an uncommon condition but is still the most likely diagnosis when a child presents with a swelling on the nose visible at or shortly after birth. Total excision is the only treatment and this may require two procedures if there is an intracranial extension. The standard vertical midline scar is a common cause of dissatisfaction. We have used an external rhinoplasty approach for this problem and feel that it gives a better exposure with a superior cosmetic result. PMID- 1914966 TI - The external rhinoplasty for the correction of unilateral choanal atresia in young children. AB - The external rhinoplasty approach has been utilized in three young children for the correction of unilateral choanal atresia. It has been demonstrated to be technically feasible to utilize this technique in young children. It provides excellent exposure of the atresia plate with the ability to correct the atresia in a precise and confident way. This technique is an elegant alternative to transnasal puncture and transeptal resection. PMID- 1914967 TI - The complications of external rhinoplasty. AB - An analysis of complications of 867 consecutive external rhinoplasties over a 14 year period is presented. The most common intraoperative complication was excessive bleeding. Transient epiphora, bleeding, excessive and/or prolonged edema, septal dematoma, transient anosmia and various problems with packing were observed in the early postoperative period. Late complications included hypertrophic scar, localized periostitis, skin telangiectasia, etc. The complications of external rhinoplasty are comparable in incidence and severity of standard endonasal rhinoplasty. PMID- 1914968 TI - Acute uvulitis in combination with acute epiglottitis: a case presentation. AB - Acute uvulitis in adults is a rare condition, especially when associated with acute epiglottitis. Watchful monitoring of the airway, usually in the intensive care unit, is recommended. Along with appropriate antibiotics and steroids, we recommend all patients with acute uvulitis have a lateral radiograph of the neck to rule out acute epiglottitis. To avoid a possible fatality, a high index of suspicion should be maintained at all times in order to appropriately diagnose and treat these patients. PMID- 1914969 TI - Juvenile aggressive fibromatosis: report of three cases and review of the literature. AB - AF is a non-encapsulated, non-metastasizing fibrous tumor that has a tendency for local recurrence in up to 70% of cases. We suspect possible genetic disposition. Microscopically, AF is a poorly circumscribed fibrous tumor that infiltrates surrounding tissues. It presents as a painless, rapidly growing mass with a predilection for bone destruction. Treatment consists of a carefully planned en bloc resection after biopsy and accurate radiologic evaluation of the extent of the tumor. Radiation therapy and chemotherapy can be used as adjuvant therapy in selected patients. Three patients with AF of the head and neck are described, of which two were found to have congenital disorders of mesodermal development. PMID- 1914971 TI - Root canal treatment: current perspectives. PMID- 1914970 TI - Use of trimethoprim & sulfamethoxazole in the treatment of nasal sarcoidosis. PMID- 1914972 TI - Root canal treatment and pulpotomy in Kenya. AB - This study was carried out to evaluate the practice and depth of knowledge of root canal treatment and pulpotomy by dentists in Kenya. Questionnaires were prepared and mailed to 114 dentists whose addresses were available. Sixty seven (58.8%) dentists responded. Of these, 67.2% carried out root canal treatment (RCT) and 43.3% carried out pulpotomy. The main reasons given by most dentists in the public hospitals for not carrying out these procedures routinely were lack of facilities and materials. Furthermore, it was found that amongst those who carried out these procedures, some used outdated techniques and materials. In order to reduce the large number of teeth lost through extraction, materials and equipment should be made available to enable dentists carry out root canal treatment and pulpotomies routinely. It is also necessary to have continuing dental education amongst dentists to update their knowledge of these procedures. PMID- 1914973 TI - Clinico-radiological aspects of dentigerous cysts. AB - The clinico-radiological features of 10 dentigerous cysts occurring in 6 patients are described. Dentigerous cysts are odontogenic cysts and may present directly as a painless jaw swelling or indirectly as an unerupted tooth. Radiologically, these cysts present as a pericoronal unilocular expansile translucencies the width of which exceeds 2.5 mm, with mandibular involvement predominating. Radiology plays an important role in detecting multiple cysts in a case presenting with a single cyst and also in detecting clinically asymptomic cysts in cases with delayed or non eruption of the teeth. PMID- 1914974 TI - Mandibular fractures: an appraisal of the weak regions. AB - There is no uniformity in the role of different aetiologic factors in mandibular fractures in different cities of the world. Cultural and socioeconomic factors appear to have important contribution to the aetiologies. The condyle and the angle-body regions are most commonly fractured. There is no obvious relationship between aetiology and the site of fracture. Structural considerations suggest that differences between dentate (open section structure) and non dentate (closed section structure) regions are important determinants of fracture sites. Some modifications of standard teaching materials are recommended. PMID- 1914975 TI - Serum thyroglobulin autoantibody titres and immunoglobulin concentrations in Nigerians with goitre. AB - Using the tanned turkey red blood cell haemaglutination test, blood samples from 327 Nigerians with goitre were screened for the presence of thyroglobulin autoantibody. 15 (4.6%) were found to have significantly positive autoantibody titres while none of the 50 age and sex-matched normal controls and autoantibody. Of the 15 with significantly positive thyroglobulin autoantibody titres, only 2 were males, giving a male:female ratio of 1 to 6.5. The mean serum concentration of IgG in the positive cases (4,163 +/- 53.5 mg/100 ml) was significantly higher than either that of normal controls (3,044 +/- 147.6 mg/100 ml) of goiterous subjects with no thyroglobulin autoantibody (2,196 +/- 116.5mg/100ml). It was found that thyroglobulin autoantibody is an IgG immunoglobulin. It is concluded that autoimmune thyroid disease occurs in Nigerians with goitre and that females are affected more than males. PMID- 1914976 TI - The Widal test in a normal healthy population in the Sudan. AB - The Widal test was performed in 114 normal individuals from the Gezira area in Sudan. Salmonella typhi O agglutinins were found at a titre of 1.320 in 12 (10.5%) of them. Salmonella paratyphi A agglutinins were found at 1.160 in 5 (4.3%) and Salmonella paratyphi B "O" agglutinins were found in 6 (5.3%) at a titre of 1.160. None of these individuals had a history of typhoid fever or vaccination with TAB vaccine. The following points emerged: (i) normal healthy people in the Sudan have high antibody titres of Salmonella typhi; (ii) the Widal test in the Sudan should be interpreted against this background; (iii) previous diagnostic titre of 1.160 for S. typhi results in high false positive results; (iv) a titre above 1.320 is suggested as diagnostic for S. typhi; 1.160 for both S. partyphi B and S. paratyphi A. PMID- 1914977 TI - Subxiphoid pericardiostomy in the management of pericardial effusions. AB - Subxiphoid pericardiostomy for diagnosis and treatment of pericardial effusion was used in 21 patients. Total evaluation of the pericardial contents, direct inspection to break down loculations, simultaneous biopsies of the pericardium and pericardial fluid samples for diagnostic tests were achieved while avoiding the need for repeated pericardiocentesis and more invasive and difficult open drainage methods. Complete drainage without recurrence was obtained in 19 patients with one death and recurrence of effusion in another one. Two of these 19 cases developed constrictive pericarditis on follow-up and required a pericardiectomy. No other complications were encountered. The procedure can be done safely under local anaesthesia for all types of pericardial effusions providing prompt and long term relief of the abnormal haemodynamics. PMID- 1914978 TI - Pathogenesis of odontogenic cysts: an update. AB - This article briefly reviews the origin, classification and pathogenesis of the various odontogenic cysts. Keratocysts and follicular cysts are said to be developmental lesions arising from the remnants of the dental lamina and the cell rests of the dental follicle respectively. The radicular cysts are the most commonly occurring lesions associated with the apices of non-vital teeth. They are said to arise from proliferation of the cell rests of Malassez in chronically inflamed granulomata. It is noted that bone resorption is the major requirement for any bony lesion to expand; hence the interest in the role of diverse cellular and chemical mediators of bone resorption in disease. The current concepts of the role, in cyst initiation and growth, of enzymes including cellular metabolites and cytokines are presented. Evidence on the activities of collagenase, arachidonic acid metabolites, leukotrienes, hydroxyeicosatetraenoic acids, interleukin--1 and prostaglandins is cited. It is observed that the understanding of these cellular and molecular biological behaviour patterns may yield more appropriate information necessary for the development of more effective management modalities for such tissue degrading lesions as odontogenic cysts. PMID- 1914979 TI - Epidemiological and clinical aspects of oesophageal carcinoma in the USA. AB - A study was conducted of all primary oesophageal cancer cases hospitalized from 1970 to 1975 in Oklahoma City hospitals. During this 6 year period, 181 cases were identified. The average annual incidence in Oklahoma county was lowest in white females (2 per 100,000 population), and highest in black males (19 per 100,000 population). Some of the descriptive features of oesophageal carcinoma by age, sex and race distribution were largely compatible to those reported in the literature. Cases with carcinoma in which pain was the first symptom to appear, sought medical advice latest compared to cases with dysphagia as the first symptom, the latter group seeking medical advice earliest. Blacks and whites presented dissimilar distribution of tumours by site. Whereas in blacks 58% of carcinomas were located in the middle thoracic and none in the oesophagogastric junction, in whites tumours were more or less equally distributed in various anatomical sites. Black males exhibited higher mean ages at diagnosis in all sites than black females. The whites showed the opposite trend except in the oesophagogastric junction. Squamous cell carcinoma was the most frequent cell type (80%). The absence of adenocarcinoma cell types in blacks except only two male cases was a noteworthy observation. The clinical stage distribution by anatomical site was unusual for middle thoracic and gastric cardia carcinomas with 54% and 46% of tumours localized and in regional stages at diagnosis respectively. PMID- 1914980 TI - Medical practice in the next century: continuing medical education for change. AB - Dramatic changes have occurred in society since the Second World War. These include great advances in science and medicine. Such changes are likely to continue at an ever increasing rate. The changes and possible implications for health care delivery over the next fifty years are discussed. These changes and their potential implications place special demands on doctors since many will still be in active practice well into the next century. To meet the challenge doctors will need to adapt to and participate in change. Continuing medical education should, therefore, aim to assist doctors to adapt to and participate in change. PMID- 1914981 TI - Skeletal and dental fluorosis: two case reports. AB - Two case reports from a high fluoride (10 ppm) rural community. They presented with severe degrees of dental fluorosis, hyper-sensitivity of teeth and skeletal fluorosis all arising from the ingestion of high amount of fluoride in water over a long period of time. Both cases had deformities of the upper and lower limbs. However, the deformities were more pronounced in the lower limbs than in the upper limbs, resulting in knock knee. Radiological finding showed osteosclerosis of the axial bones while the appendicular bones exhibited osteoporosis. There was marked change of bone structure observed as osteomalacia, and course trabecular bone pattern. Osteoporosis was also associated with cortical thinning. Periosteal bone apposition was observed in the bones: and genu valgum of the limbs. Biochemical tests revealed normal values for serum calcium and inorganic phosphate. However, the serum alkaline phosphatase was elevated. This may be an indication of a pathological condition where there are possible compensatory mechanisms to maintain normal levels of serum calcium and inorganic phosphate. One case which had undergone corrective surgical intervention of the lower limbs four years earlier, had continued to live in the same environment using drinking water with 10 ppmF after corrective surgery, and showed no improvement. PMID- 1914982 TI - Fibrous dysplasia of the jaws: a case report. AB - This article reviews the present clinical, radiographic and histologic features of fibrous dysplastic lesions of the jaws. A case is presented of an apparently reactivated fibrous dysplastic jaw lesion, with evidence of cystic degeneration, in a 33-year-old female school-teacher who was first seen at the Department of Dental Surgery, University of Nairobi in March 1986. The dilemma in the management of fibrous dysplasia is reviewed and discussed. It is noted that while conservative surgical procedures remain the treatment of choice, situations arise where tremendous tissue activity would require early intervention by numerous cosmetic surgical shaving procedures. The present case, however, offers a unique management challenge due to the occurrence of extensive cystic degeneration in the mandible. PMID- 1914983 TI - Patterns of oxygenation during periodic breathing in preterm infants. AB - The characteristics of the arterial oxygen saturation (SaO2) signal during episodes of hypoxaemia (SaO2 less than or equal to 80% for greater than or equal to 4 s) associated with periodic and non-periodic apnoeic pauses were studied in 16 preterm infants with cyanotic episodes (patients). and 15 asymptomatic preterm infants (controls), matched on birthweight and gestational age. The patients showed a significantly higher percentage of apnoeic pauses followed by a hypoxaemic episode (25 vs. 6%, P less than 0.01), and a two-fold increase in the slope of the desaturation curve (8.4 vs. 4.3% per s, P less than 0.005) in periodic compared with non-periodic breathing. All other characteristic of oxygenation (baseline SaO2 before episodes of hypoxaemia, delay between onset of apnoeic pause and onset of desaturation, lowest SaO2 during episodes of hypoxaemia) were similar for periodic and non-periodic breathing patterns. Similar, but not significant, differences between isolated and periodic apnoeic pauses were also present in the controls. An analysis of episodes of bradycardia (less than or equal to 100 beats per minute (bpm] showed that out of 121 episodes in the patients 118 were accompanied by a fall in SaO2 to less than or equal to 80%, and in the remaining three SaO2 fell to 82%, 85% and 86%, respectively. Thus all episodes of bradycardia (less than or equal to 100 bpm) were associated with a fall in SaO2 detected by beat-to-beat pulse oximetry. Examination of hypoxaemic episodes and their relationship with bradycardia and with apnoeic pauses, periodic and non-periodic, may help the further understanding of the control of arterial oxygenation in preterm infants with cyanotic episodes. PMID- 1914984 TI - Growth retardation and the development of the respiratory system in fetal sheep. AB - In an experimental model of fetal growth retardation which involves the reduction of placental mass in ewes, we have investigated the effects of intrauterine deprivation on aspects of structural development of the trachea and lungs of fetal sheep (140 days gestation). We have also measured the volume of luminal liquid aspirated from the lungs and the phospholipid content of this liquid as an index of pulmonary surfactant production. The effects of growth retardation are evident in the trachea where the structural development of the mucosal and submucosal layers has been affected. Abnormal aspects of development include the frequent lack of a ciliated border on epithelial cells in the mucosal layer and the reduction in the extent of the folds usually characteristic of this layer in near term fetal sheep. Although the fetal lungs are smaller in growth retardation (P less than 0.01) they are appropriate for fetal weight and their structural development does not appear to have been retarded. In contrast, lung liquid volume is significantly reduced in relation to lung weight in growth retarded fetuses and the concentration of phospholipids in lung liquids is also reduced (P less than 0.01). PMID- 1914985 TI - Home oxygen therapy following neonatal intensive care. AB - In a 12-month period 28 of 164 consecutive very low birthweight (VLBW) infants receiving intensive care within 48 h of birth at King's College Hospital developed chronic lung disease, (oxygen dependence beyond 28 days of age). Fifteen of the 28 infants were eligible for home oxygen therapy, but this was only practical, because of home circumstances, in 8 infants (4.9%). These 8 infants received home oxygen therapy. One further infant, born at term and suffering from pulmonary hypoplasia was also discharged home on oxygen therapy. Two infants subsequently required readmission due to a deterioration in their respiratory status and died. Three others required re-admissions (total duration 32 days) for respiratory problems. The median duration of home oxygen therapy was 17 weeks (range 4-486 days). We conclude that home oxygen therapy is needed by only a very small number of preterm infants and is appropriate for only a proportion of them. Parents need to be counselled carefully regarding the possibility that the need for oxygen might be protracted. PMID- 1914986 TI - A chest radiograph scoring system to predict chronic oxygen dependency in low birth weight infants. AB - The usefulness of a chest radiograph scoring system to predict chronic oxygen dependency (oxygen dependency at 36 weeks post conceptual age) was determined in 40 infants with a median gestational age 27 weeks (range 24-32 weeks). The scoring system assessed the appearance of the preterm infant's chest radiograph taken at one month of age, and graded the radiograph according to lung volume, the presence of opacification, cystic elements and interstitial change (maximum score 24). Infants who were chronically oxygen dependent had significantly higher scores (median 9, range 7-20) than those not oxygen dependent (median 3, range 0 13, P less than 0.01). All nine chronically oxygen dependent infants had a score greater than 6, in comparison with only two of 31 infants not chronically oxygen dependent (P less than 0.01). A chest radiograph score of 6 thus had a sensitivity of 100% and specificity of 93.5% in predicting chronic oxygen dependency. PMID- 1914987 TI - The natural history and predictive value of early language delays in very low birth weight infants. AB - A cohort of 28 VLBW (less than or equal to 1500 g) infants was assessed at 1 and 3 years of age for hearing, language development and neurological status. Language delays were detected in 11 (39%) infants at 1 year, and in four (15%) at follow up at 3 years of age (P less than 0.05). Language quotients were significantly associated with perinatal variables at 1 but not at 3 years of age. Infants with neurological abnormalities had significantly lower language quotients at the 3-year follow up. No child with a normal language profile at 1 year exhibited a delay at 3 years of age. PMID- 1914988 TI - Delayed neurological adaptation in infants delivered by elective cesarean section and the relation to catecholamine levels. AB - We have studied the effect of mode of delivery and catecholamine (CA) surge at birth on neurobehaviour 1, 2 and 5 days after birth. Fifteen full-term infants were delivered by elective cesarean section (CS) and 15 full-term control infants were born vaginally. Infants born after elective CS were less excitable and had significantly reduced number of optimal responses during the first 2 days after delivery, compared to the controls. On the 5th day no significant neurological differences were found between the groups. Adrenaline and noradrenaline (NA) in umbilical arterial plasma were analysed in all infants. The mean values of NA were lower in the CS infants as compared to the vaginally delivered infants. Statistically significant correlations were found between low CA levels and poor muscle tone and/or lower grade of excitability in the CS infants. These results suggest that the high CA surge at birth might be of importance for the neurological adaptation after birth. PMID- 1914989 TI - At what age is the developing cerebral cortex of the rat comparable to that of the full-term newborn human baby? AB - By means of a comparative study of experimental data from the literature we estimated at what age the rat cerebral cortex corresponds to that of the full term newborn human infant with regard to the degree of maturation. As a result of this study we suggest that the 12-13-day-old rat pup fulfills this criterion. This finding should be of use to scientists who use the rat for studying certain processes assumed to occur in the human cerebral cortex around full-term birth. PMID- 1914990 TI - Inflating pressures for effective resuscitation of preterm infants. AB - The magnitude of inflating pressure necessary for effective resuscitation was examined in 70 preterm infants. The median pressure to cause adequate chest wall expansion was 22.8 cmH2O; no infant required a peak inflating pressure greater than 30 cmH2O. No further increase in inflation pressure was used during resuscitation and the median 5- and 10-min Apgar scores were 8 and 9, respectively. PMID- 1914991 TI - An early life-stage test with Daphnia magna Straus: an alternative to the 21-day chronic test? AB - Chronic life-cycle tests using the freshwater cladoceran Daphnia magna aim to measure the effect of toxic chemicals on adult reproduction, in terms of the number of viable offspring produced. A tacit assumption is made that the primary effect of toxicants in these tests is a sublethal effect on the parent, reducing egg production and hence fecundity. The authors' observations on two chemicals, sodium bromide and 3,4-dichloroaniline, demonstrate that this assumption is at least partly false. In these experiments, the primary toxic effect of these compounds was to kill developing eggs in the brood chamber. Total egg output was unaffected, whereas output of viable eggs was severely impaired--an acute lethal effect. A further experiment demonstrated that the effect was limited to those eggs developing in the brood chamber, with eggs in the ovary remaining unaffected. It was suggested that these observations may provide the basis for the development of a short, sensitive early life-stage test with this species. PMID- 1914992 TI - A comparison of the sensitivity of three Daphnia magna populations under chronic heavy metal stress. AB - The results from chromium, nickel, and zinc bioassays with three populations of Daphnia magna indicate that the investigated strains are differently sensitive. Sublethal concentrations which have a negative effect on survival and reproduction after 21 days of exposure also cause a significant reduction in the body length and brood size of primiparous females. Problems and consequences of the repeatability of such bioassays between laboratories in different countries are discussed. PMID- 1914993 TI - Protein degradation and related enzyme profiles on a sublethal toxicity of aldrin in the tissues of Rana hexadactyla. AB - The effects of a sublethal toxicity of aldrin were studied in the brain, muscle, kidney, and intestine of Rana hexadactyla after 1, 2, and 4 weeks of exposures. Aldrin toxicity resulted in a depletion of protein, an increase in amino acid levels, and an enhancement of the activity of protease and amino transferases. The changes were maximum after a 4-week exposure. PMID- 1914994 TI - Changes in adrenocortical-pituitary activity in the catfish, Clarias batrachus (L.), after mercury treatment. AB - The toxic effects of mercuric chloride (HgCl2), emisan 6 (a methoxy-ethyl mercury fungicide), and methyl mercuric chloride (CH3HgCl) on the adrenocortical pituitary activity of the catfish were investigated after 45, 90, and 180 days of exposure. The adrenocortical cells were highly stimulated in the 90-day HgCl2 group and became hyperplastic in the 180-day group. These cells were active in the 90-day emisan 6 group, with the infiltration of lymphocytes and fibrosis in the 180-day group. In the 90-day CH3HgCl gropu, the cells were active, with lymphocytic infiltration, fibrosis, and necrotic changes in some areas. In the 180-day CH3HgCl group, there was an extensive infiltration of lymphocytes, with localized sites of necrosis and hyperplasia. The ACTH cells in the pituitary were hypertrophied and degranulated in the Hg-treated groups, suggesting increased secretion of ACTH. The plasma cortisol level decreased significantly in the 90- and 180-day Hg-exposed groups in a time-dependent manner. Of the three mercurials, CH3HgCl is the most toxic in reducing the plasma cortisol level in all durations. These results suggest that Hg impairs the adrenocortical-pituitary activity of the catfish. PMID- 1914995 TI - Seasonal and sex-linked variations in hepatic and extrahepatic biotransformation activities in striped mullet (Mullus barbatus). AB - Microsomal cytochrome P450 content, NADPH-cytochrome c reductase, and phase I (ethoxycoumarin and ethoxyresorufin O-dealkylases) and phase II (glutathione S transferase and UDP-glucuronyltransferase) activities were studied in the liver and intestine of the striped mullet (Mullus barbatus) for 8 months (before and during sexual maturation). Biotransformation activities were much lower in extrahepatic tissues than the corresponding activities in the liver. Intestinal and hepatic biotransformation activities presented similar seasonal fluctuations: Phase I activity increased from October to February (during water cooling) and generally decreased before spawning; Phase II activity was not greatly different. Moreover, NADPH-cytochrome c reductase, ethoxyresorufin O-dealkylase, and glutathione S-transferase activities were measured in the kidney during the sexual maturation period. Renal phase I and phase II activities showed very little fluctuation during the 5 months studied. Cytochrome P450 and ethoxycoumarin and ethoxyresorufin O-dealkylases exhibited sex-linked differences during sexual maturation, whatever the tissue: in the liver the values are higher in male fish, whereas in the intestine and kidney they are lower. PMID- 1914996 TI - Present mercury levels in red blood cells of nearby inhabitants about 30 years after the outbreak of Minamata disease. AB - Samples of red blood cells (RBCs) from 1178 inhabitants, consisting of 546 males and 795 females (over 40 years old), of a coastal town near Minamata City were analyzed for total mercury. The mercury concentrations in the RBCs showed lognormal distributions for both sexes with higher values in males than in females. The geometric mean of the mercury concentrations in the RBCs was 27.5 ng/g (ranging from 8.0 to 69.1 ng/g) for males and 20.4 ng/g (ranging from 7.0 to 63.7 ng/g) for females. The mercury concentrations in the RBCs decreased with advancing age. A significant regression between the geometric mean of the mercury concentrations in the RBCs and age was obtained for both sexes. The mercury concentrations in the RBCs from male inhabitants of the coastland area were significantly higher than those from male inhabitants of the inland area. In terms of occupation, the highest mercury concentrations were observed in the RBCs from fisherman. No significant difference in the present mercury concentrations in the RBCs was observed between the cases with Minamata disease and the controls. PMID- 1914997 TI - Effects of organophosphorus insecticides: effects of trichlorfon and dichlorvos on the immune response of carp (Cyprinus carpio). III. In vitro effects on lymphocyte proliferation and phagocytosis and in vivo effects on humoral response. AB - Cells isolated from the pronephros of carp were incubated in vitro with the organophosphorus insecticide trichlorfon or dichlorvos, each of which is used in aquaculture to eliminate fish ectoparasites. Dose-dependent suppressive effects were observed in assays for lymphocyte proliferation and myeloid cell respiratory burst activities. Dichlorvos given by bath in vivo did not affect antibody production against Yersinia ruckeri even if the spleen and kidney were obviously contaminated according to acetylcholinesterase activity analysis. Some blood parameters of nonspecific immunity (ceruloplasmin, lysozyme, hemagglutinins) were slightly affected. PMID- 1914998 TI - Impact of insecticides on nontarget microarthropod fauna in agricultural soil. AB - Ecologically important soil microarthropods were used to evaluate the direct and residual toxicities of some insecticides under field and laboratory conditions. The density of total microarthropods and major groups, namely Acarina and Collembola, suffered a statistically significant and persistent decline in the aldrin 30 EC (0.25%)- and endosulfan 35 EC (0.33%)-treated soil of wheat fields. But dimethoate 30 EC (0.125%) and phosphamidon 85 EC (0.03%) applied in mustard fields produced only a temporary decline. Laboratory studies showed that all the above insecticides and monocrotophos 36 EC (0.2%), methyl parathion 50 EC (0.05%), chlordane 20 EC (0.125%), and carbaryl 50 WP (0.625%) had a direct knockdown effect on Cyphoderus sp. but another collembolan species, Xenylla sp., appeared to be somewhat resistant. Only endosulfan was toxic to a common soil Acarina species, Lancetoppia sp. Among four soil media, toxicity was maximum in pure sand, followed by sandy loam, clay, and organic soil. The residual toxicity of phosphamidon, dimethoate, methyl parathion, and endosulfan was more prolonged for Cyphoderus sp. than for Xenylla sp. Only the larval stage of Lancetoppia sp. was susceptible to the residual effect of endosulfan. LD50 and bioassay studies showed that Cyphoderus sp. can be employed as a potential biomonitor of insecticide pollution in soil. PMID- 1914999 TI - Effects of lead on kinetics of 3H-dopamine uptake by rat brain synaptosomes. AB - The effects of lead on 3H-dopamine (3H-DA) uptake in rat brain synaptosomes were studied. Pb inhibited 3H-DA uptake in vitro and in vivo in a concentration dependent manner. Altered pH versus 3H-DA uptake demonstrated comparable inhibition in buffered acidic, neutral, and alkaline pH ranges, and higher inhibition was observed in neutral pH. Kinetic studies of ATP activation of 3H-DA uptake indicated competitive inhibition by Pb. The inhibition of 3H-DA uptake followed the Na+ concentrations. The results indicate that the Pb inhibition of 3H-DA uptake is pH, ATP, and Na+ dependent. PMID- 1915000 TI - The genetic toxicology of organic compounds in natural waters and wastewaters. AB - This review was drawn from the literature describing genotoxic organic compounds in natural water (rivers, lakes, streams) and wastewater, as well as from recent discussions with industrial scientists and environmental regulators. Testing of wastewaters for genotoxicity may become a routine requirement for some industrial wastewater discharge permits, not unlike the more common requirement for routine aquatic toxicity tests. The stimuli for this are concerns that aquatic organisms inhabiting waters impacted by wastewater discharges suffer an increased risk of genetic damage or cancer, and that humans utilizing these waters for recreational and drinking water purposes may suffer similar genetic or carcinogenic risks. Some evidence suggests that neoplasia in aquatic organisms is related to habitat contamination, yet field evaluations fail to substantiate adequately a cause-and effect relationship. Because aquatic organisms respond like mammals to the same genotoxic compounds, the increased burden of genotoxic compounds to the environment may impact certain endemic species. Wastewater discharges may be one source of genotoxic organic compounds in those impacted areas. With respect to potential human health impacts, evidence is supportive of increased cancer risk to individuals drinking water from surface sources; however, this risk may or may not relate to whether the drinking water source received input of wastewater discharges or known carcinogens. Throughout the published literature reviewed herein, the Salmonella/Ames gene mutation test was widely used to assess genotoxic activity, although studies using indigenous plants and aquatic organisms as in vivo monitors of genotoxic activity exist. No "standard" or frequently followed protocols for sample collection, sample processing, selection of tests or their conduct, or interpretation of data exist for most of the genotoxicity studies reviewed. For the Salmonella/Ames test, the aqueous samples were concentrated usually on XAD resin or by liquid:liquid extraction, and without this concentration step few samples exhibited genotoxic activity. Hence, in most instances, the ambient concentration of the compounds causing this activity is below that which is readily detectable by this test, a finding not new to this review. In contrast, aquatic organisms in laboratory and field studies responded to ambient concentrations of genotoxic compounds, thus alleviating the need for sample concentration. However, there appears to be a reluctance to utilize this information for extrapolation to potential human health effects. Unfortunately, no generally accepted and scientifically validated protocol for preparing aqueous samples for genotoxicity testing exists. Developing such a protocol is necessary before embarking on widespread genotoxicity testing of wastewaters, especially if results are to be used for permit compliance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915001 TI - [Curriculum evaluation for clinical education in nursing]. PMID- 1915002 TI - [Economic characteristics of liberal medicine]. PMID- 1915003 TI - [Teaching-care integration in dentistry in Brazil]. PMID- 1915004 TI - [Nicaragua: reflections on the situational strategic planning of the health work force]. PMID- 1915005 TI - [Nursing research in Latin America]. PMID- 1915006 TI - [Continuing education of health personnel: the experience in Costa Rica]. PMID- 1915007 TI - [Review of the content of policy, economics, health planning and legislation in the programs of the public health schools in the United States of America]. PMID- 1915008 TI - [Health education: methodological aspects]. PMID- 1915010 TI - Perception or action: some comments on preparatory negative potentials. PMID- 1915009 TI - [Analysis of learning in a workshop on primary health care]. PMID- 1915011 TI - Neuromagnetic studies of sensory functions and mental imagery. PMID- 1915012 TI - Stimulant drugs and ERPs. PMID- 1915013 TI - Contingent negative variation (CNV) in psychopharmacology. PMID- 1915014 TI - Discussion: towards a pharmacology of information processing. PMID- 1915015 TI - Visual-spatial attention: preparation and selection in children and adults. PMID- 1915016 TI - Mechanisms of auditory selective attention as revealed by event-related potentials. PMID- 1915017 TI - The search for 'neutral' conditions for recording control event-related potentials in order to assess cognitive components to both irrelevant and relevant stimuli: evidence for short-latency cognitive somatosensory effects. PMID- 1915018 TI - ERPs and selective attention: commentary. PMID- 1915019 TI - Selective attention and mental chronometry. PMID- 1915020 TI - Separation and identification of event-related potential components by brain electric source analysis. PMID- 1915021 TI - Discrete versus continuous information processing: introduction and psychophysiology. PMID- 1915022 TI - Continuous versus discrete information processing: evidence from movement-related potentials. PMID- 1915023 TI - Brain control of cardiovascular dynamics. PMID- 1915024 TI - The electroencephalogram and evoked potentials in normal aging and dementia. PMID- 1915026 TI - Arousal and effort: a review and theoretical synthesis of studies of age-related changes in event-related potentials. PMID- 1915025 TI - P300 in the evaluation of aging and dementia. PMID- 1915027 TI - ERPs and brain structure: relationships across the adult age span in alcoholics and in a patient with herpes simplex encephalitis. PMID- 1915028 TI - Cerebral function in aging and Alzheimer's disease: the role of PET. PMID- 1915029 TI - Localization of brain sources of visually evoked responses: using single and multiple dipoles. An overview of different approaches. PMID- 1915030 TI - Physiological sources of evoked potentials. PMID- 1915031 TI - Topographic representation of event-related potentials. PMID- 1915032 TI - Event-related desynchronization during motor behavior and visual information processing. PMID- 1915033 TI - Activity of single neurons in monkey cortex preceding sensory cued limb movements. PMID- 1915034 TI - Cortical potentials associated with voluntary movements in monkeys. PMID- 1915035 TI - Functional localisation of motor processes in the human cortex. PMID- 1915036 TI - Transcranial facial nerve stimulation by magnetic stimulator in normal subjects. AB - Magnetic stimulation provides a new method to stimulate facial nerve transcranially. Stimulation can be directed to the intracranial part of the facial nerve, whereas the conventional electric stimuli are delivered extracranially to a more peripheral part of the nerve. Fourty healthy volunteers were examined to determine the normal responses for transcranial facial nerve stimulation. The center of the inducing coil ring was located so that its center was 3 cm posterior and 6 cm lateral to the vertex. Responses were recorded on the nasolabial fold. Latencies were 4.5 +/- 0.4 ms on both sides, being 1.1 ms longer than those elicited by electric stimulation of the nerve at the stylomastoid foramen. Amplitudes with magnetic stimuli were equal to those obtained with electric stimuli. The transcranial magnetic stimulation seems to be an accurate and promising method to examine the facial nerve. PMID- 1915037 TI - Conduction velocities and nerve fibre diameters of touch, pain, urinary bladder and anal canal afferents and alpha and gamma-motoneurons in human dorsal sacral roots. AB - 1. Single action potentials were recorded extracellularly at 2 sites from human sacral dorsal nerve roots, and their conduction time measured. Conduction velocity frequency distribution histograms were constructed from afferent and efferent nerve fibres. Conduction velocity distribution peaks could be identified from afferents of mechanoreceptors of the skin, the bladder, the anal canal, of stretch and flow receptors of the urinary bladder, from spindle afferents and from the 3 alpha (extrafusal) and 3 gamma-motoneuron (intrafusal) classes. The electrophysiologically measured roots were removed and morphometrically analysed. Nerve fibre diameter frequency distribution histograms were constructed with respect to 3 myelin sheath thickness ranges. Nerve fibre diameter distribution peaks could partly be correlated to the corresponding conduction velocity distribution peaks. 2. Identified nerve fibre classes, characterized by their group peak values of conduction velocity and fibre diameter were at about 36 degrees C (age 30 years): Spindle afferents: SP1 (60 msec-1/13.2 microns) SP2 (50/12.0?); touch afferents: TO (49 msec-1/13.0 microns), T1 (44/11.2), T2 (39/10.1), T3 (31/9.1), T4 (20/8.3); pain afferents: P (13 msec-1/?); mucosa touch afferents from bladder and anal canal: M (12.5 msec-1/?); bladder afferents from stretch receptors measuring probably mural tension: S1 (42.5 msec-1/?), ST (38/?) and from flow receptors: S2 (12.5/?); alpha-motoneurons: alpha 1 (60 msec 1/13.1 microns) [FF], alpha 11 (?/12.0) [F (int)], alpha 2 (50/10.2) [FR], alpha 3 (37/8.3) [S]; gamma-motoneurons: gamma beta (27 msec-1/7.2 microns), gamma 1 (20/6.7), gamma 2 (15/6.2). 3. Because of the strong temperature dependence of the conduction velocities a calibration of the structure of the velocities, which was almost independent of temperature, is defined by the condition that the alpha 2-motoneurons have the same peak conduction velocity then the secondary spindle afferents (SP2); the T1 touch afferents have about 10% lower velocity values. 4. Touch afferents and alpha-motoneurons had a different velocity-diameter relation, which indicated differences in the myelin sheath thickness and/or membrane properties. The conduction velocities of the touch afferents were more temperature-dependent than those of the alpha-motoneurons. Within the classes of touch afferents and alpha-motoneurons the temperature dependence increased towards smaller class peak values. 5. Through the use of action potential wave form comparisons it was possible to identify action potentials from single nerve fibres in each class of touch afferents (T0 to T4). Activity patterns of single touch units could partly be analysed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915038 TI - Fourier series analysis of the electrophysiological pattern of fatigue in healthy human beings, after curare administration. AB - Real time computer analysis of the electrophysiological development of muscular fatigue after small doses of d-tubocurarine (TC), has been examined in anesthetized human beings. As compared to a decrease of frequency in the control measurements, previous studies have shown an increase of the frequency of spikes after TC administration. The present experiments were carried out on the biceps brachii of 8 healthy human volunteers maintained in isometric contraction against a constant counter load until complete fatigue occurred. The Fourier spectrum analysis showed a statistically significant shift to lower frequencies before, and a milder statistically non significant shift after TC. These results may indicate that under mild curarization the early phase of muscular contraction requires a higher number of large motor units and thus, at a later stage of the contraction the pool of available large motor units becomes smaller. This conclusion supports the hypothesis that mild curarization causes a state of initial muscular fatigue. PMID- 1915039 TI - Magnetic motor evoked potentials (MEPs) in masseter muscles. AB - Electromyographic responses of the masseter muscles and orbicularis oris muscles following transcranial magnetic stimulations were recorded with surface and needle electrodes. MEPs in masseter muscles (latency 6.9 +/- 0.71 ms, mean +/- SD) due to activation of controlateral cortico-nuclear connections were evoked by magnetic stimulations at 4 cm laterally to the vertex on the biauricular line. These MEPs were followed bilaterally by a silent period lasting about 20 ms and, less constantly, by a later silent period lasting up to 80 ms. The ipsilateral responses to the same stimuli presented shorter latencies and higher amplitudes and they were ascribed to direct stimulation of the trigeminal nerve, probably its intracisternal portion. Ipsilateral masseter "cortical" MEPs could be elicited only by a lower output setting (70% of the maximum output) of the stimulator. Orbicularis oris MEPs were polyphasic and dispersed with latencies ranging from 7 to 11 ms. In patients with hemispheric or capsular ischemic lesions "cortical" MEPs were absent when stimulating the affected hemisphere and present when stimulating the unaffected one. We suggest that the direct corticomotoneuronal projections for the masseter are mainly crossed. PMID- 1915040 TI - Fibrillation potentials do not originate in type 1 muscle fibers? AB - Electrophysiological and muscle histochemical studies of denervated muscle were performed simultaneously in order to determine the relationship between fibrillation potentials and muscle fiber type. Fibrillation potentials recorded in the soleus muscle 2 weeks after resection of the sciatic nerve revealed a lower firing rate than in the extensor digitorum longus (EDL) muscle of the same rats. The majority of muscle fibers stained for adenosine triphosphatase (ATPase) activity after preincubation at pH 9.4, 4.6, and 4.3 in the soleus muscle were type 1 fibers, while most of those in the EDL were of type 2. Moreover, one of the rats, which demonstrated no fibrillation potentials in the soleus muscle, was found to have no type 2A or 2B fibers histochemically, in the same soleus muscle. These findings suggest that fibrillation potentials may not originate in type 1 fibers. PMID- 1915041 TI - Stapedius reflex decay test in diagnosis of myasthenia gravis (MG). AB - Stapedius reflex decay test (SRDT) was attempted in 30 patients with suspected myasthenia gravis (MG). In 43% of the sample measurement of the decay was not possible because of an audiologic abnormality, reflex threshold too high for safe testing or absence of the reflex with no obvious cause. A control group of 24 normal subjects showed a large variance and thus only a decay, after 5 minutes of stimulation, greater than 50% of the original value was considered abnormal. Out of 17 patients in whom SR decay was successfully measured, 7 (41%) had an abnormal value. Sensitivity of the test was found at 80%, specificity at 75%, when the clinical diagnosis of MG, upheld in follow-up, was taken as a criterion. The percentage of concordant abnormal findings was 50% for repetitive electrical stimulation of a peripheral nerve, 60% for positive effect of anticholinesterase drugs, 100% for presence of ACh receptor antibodies. PMID- 1915042 TI - Imaging after head trauma. Who needs what? AB - Decisions about the optimal imaging strategy in patients after acute head trauma can be based on clinical observations. Low-risk patients do not require radiographic imaging. CT is the procedure of choice for imaging moderate- and high-risk patients after head trauma. Because of its limited ability to guide therapy, plain skull radiography should be used sparingly; it may be useful in equivocal cases of bony injury not detected by CT or in selected moderate-risk patients (especially children under the age of 2 years). MR imaging rivals CT in the detection of intracranial injuries but is more expensive and cumbersome in seriously ill subjects and does not image bony structures. MR imaging is recommended after initial CT if subtle acute nonhemorrhagic and subacute hemorrhagic lesions are suspected, especially in the evaluation of child abuse. Otherwise, MR imaging is rarely needed in the emergency department management of acute head injury patients. PMID- 1915043 TI - Focus on radiology: Part I. PMID- 1915044 TI - Imaging of the atlas (C1) and axis (C2). AB - In imaging the atlantoaxial region in injured patients, the initial modality is plain radiography. The lateral C-spine as well as the open-mouth view are essential in this regard. On these views, it is not only important to examine the bony contour but also to look for indirect signs of injury such as prevertebral soft-tissue swelling, air in the prevertebral space, an increased width of the anterior atlantodental interval, and overriding of the C1-C2 joint on one side (the so-called wink sign of atlantoaxial rotatory subluxation). In patients in whom there is a high index of suspicion for occult trauma, but without fractures suggested or adequately visualized on routine films, or in those with severe cranial trauma, further studies should be pursued. CT scan is the modality of choice in optimally imaging the bony contours of the axis and atlas. It has limitations in visualizing transversely oriented fractures such as high dens fractures, transverse fractures of the facet joints (although widening of the facet joint is an indirect indication of facet fracture), or transverse arch fractures. Plain tomography may better demonstrate such transverse fractures but has several disadvantages. Plain tomography is often not as readily available as CT; it requires that the patient be placed in lateral decubitus position to obtain lateral tomograms, which may be contraindicated in such clinical circumstances; and it is not as easy to appreciate three-dimensional relationships on plain tomography as it is on CT. CT clearly defines the location of displaced bone fragments in relationship to the spinal canal as well as often demonstrating disc injuries. Ligamentous injury, though potentially visualized directly on MR imaging, is more commonly addressed with flexion-extension films. Flexion-extension studies should, obviously, be performed only in awake, oriented patients who are without neurologic deficit, and the studies should be done with close physician supervision and stopped at the first onset of pain. MR imaging may be helpful in demonstrating soft-tissue injuries such as hemorrhage, disc herniation, nerve root impingement, and direct spinal cord damage. PMID- 1915046 TI - Paranasal sinus radiography. AB - Infections of the paranasal sinuses are often seen in the Emergency Department. The use of plain film radiography is a safe and rapid way to confirm the diagnosis of such an infection. This article reviews the paranasal anatomy and appearance of non-neoplastic paranasal sinus diseases on plain films. PMID- 1915045 TI - Facilitating cervical spine radiography in blunt trauma. AB - The interpretation of cervical spine radiographs is an important facet of the evaluation of blunt trauma victims. The diagnostic accuracy of cervical spine films is dependent upon the technical adequacy of the radiographs and the clinician's diagnostic and interpretive skills. The anxiety inherent in cervical radiographic interpretation by the nonradiologist can be minimized by coupling the use of several simple techniques aimed at enhancing visualization of all cervical spine elements and optimizing bony definitions with an unhurried, methodical radiographic evaluation utilizing a number of radiologic "pearls" in those instances in which injury is less than readily apparent but still suspect. PMID- 1915047 TI - Upper airway obstruction in the pediatric patient. PMID- 1915048 TI - The portable chest film. AB - This article presents specific uses of the portable chest film. The specific utility, borderline utility, and pitfalls in interpretation of films that are often taken to investigate a number of diagnostic problems common to the practice of emergency medicine are discussed. PMID- 1915049 TI - Traumatic rupture of the thoracic aorta. AB - Because the diagnosis of a traumatic rupture of the aorta can be subtle, a high index of clinical suspicion must be maintained to arrive at a prompt and correct diagnosis. When chest radiography shows that the mediastinum is greater than 8 cm in width or that the arch or descending aorta are obscured, direct transfemoral arteriography remains the procedure of choice in hemodynamically stabilized patients. At the present time, computed tomography is not recommended as a definitive diagnostic modality. PMID- 1915050 TI - Ventilation-perfusion scintigraphy. AB - Ventilation-perfusion scintigraphy remains an important diagnostic tool in the evaluation of patients suspected of having PE. It is important for the emergency physician to be able to use the information from a lung scan appropriately in the diagnostic management of this elusive and life-threatening disorder. This requires a clear knowledge of how these scans are interpreted as well as a consultative approach between the physician ordering the lung scan and the nuclear medicine physician interpreting it. Each can ultimately contribute to the development of an effective management plan. It is important for the clinician to understand that a low-probability lung scan does not rule out PE, but in fact can have up to a 40% probability of PE when clinical suspicion is high. PMID- 1915051 TI - Emergency abdominal radiography. AB - Plain abdominal radiographs are rarely diagnostic when the patient presents with acute abdominal pain. Emergency physicians, therefore, should be aware of the appropriate indications and limitations of abdominal films in this setting and should be skilled in their interpretation to exclude the rare cases of pneumoperitoneum, pneumobilia, hepatic-portovenous gas, small and large bowel obstruction, toxic megacolon, volvulus and intramural gas. PMID- 1915052 TI - Hepatobiliary imaging. AB - A patient's clinical presentation should prompt an imaging evaluation that is cost effective for accurate diagnosis and leads to appropriate treatment of gallbladder inflammatory disease. In the setting of recurrent biliary colic, chronic cholecystitis is the main diagnostic consideration. Imaging hallmarks include gallstones and gallbladder wall thickening for which ultrasonography is uniquely suited. When a patient appears more toxic with right upper quadrant pain, one would more strongly consider acute cholecystitis. Because the morbidity and mortality of acute cholecystitis are reduced with early cholecystectomy, it is incumbent upon the clinician to make the diagnosis promptly and accurately. Hepatobiliary imaging with an IDA derivative has proven superior sensitivity, specificity, and accuracy for this condition. The examination has validity because it detects cystic duct obstruction, the primary pathophysiologic event responsible for most acute calculous and acalculous disease. Utilizing morphine augmentation when delayed filling is present has reduced the total examination time to less than 2 hours. Use of ancillary findings including gallbladder hyperemia and the "hot rim" sign help predict complicated cholecystitis, enabling more urgent intervention. The bulk of data presented in this review supports hepatobiliary imaging as the modality of first choice in the evaluation of acute cholecystitis. In the intensive care setting, where acalculous disease and atypical presentations are common, hepatobiliary imaging also plays a major role. We recommend liberal use of Sincalide pretreatment, morphine augmentation, and delayed images to promote gallbladder filling. If the gallbladder is nonvisualizing despite these maneuvers, sonography is often added as an aid to detect secondary signs of acute cholecystitis and help confirm the diagnosis with greater certainty prior to high-risk surgery. PMID- 1915053 TI - City mouse--country mouse. Urban versus rural radiology support. AB - In summary, the radiologic aspect of the emergency medicine practice in a rural setting usually involves doing a satisfactory job with less than you have at your disposal in a city practice or training program. Good communication with the radiologist and a solid knowledge of what can and cannot be done with the available equipment will save you aggravation and, possibly, litigation. PMID- 1915054 TI - Quality assurance for the radiology-emergency interface. AB - Quality assurance does not have to be a dirty word. Developing indicators, identifying trends, taking action, and reassessing the results can significantly benefit the technical and nursing staff, emergency physicians, radiologists, and, especially, the patients. PMID- 1915055 TI - The backstage story of the discovery of LHRH. PMID- 1915056 TI - Why I was told not to study inhibin and what I did about it. PMID- 1915057 TI - Remembrance of H. W. Magoun's contributions to the development of neuroendocrinology. PMID- 1915058 TI - Remembrance project: origins of RIA. PMID- 1915059 TI - Estrogen induction of growth hormone in the thyroidectomized rat. AB - GH production in the rat is almost completely dependent upon T3. Estrogens also stimulate GH in some rat models, and androgens have well documented stimulatory effects. This study examined estrogen and androgen effects on pituitary GH in rats with differing thyroid status. Diethylstilbesterol (DES; a potent synthetic estrogen, 5 mg Silastic implant), estradiol benzoate (50 micrograms/kg.48 h), or testosterone propionate (10 mg/kg.48 h) were administered for 3 weeks to ovariectomized rats that were either thyroid-intact or thyroid-ectomized. In intact rats, DES produced a 40% decrease in pituitary GH, whereas estradiol (at a lower relative dose) had no effect; testosterone produced a 65% increase in pituitary GH. Thyroidectomy decreased pituitary GH to less than 0.5% of intact values. DES and estradiol produced 50- to 70-fold increases in pituitary GH in thyroidectomized rats--reaching 23-36% of intact levels. In contrast, testosterone had no effect in thyroidectomized rats. Tamoxifen (an antiestrogen; 1 mg/kg.24 h) increased GH by 15-fold in thyroidectomized rats and completely blocked further GH induction by estradiol. T3 (20 micrograms/kg.24 h) increased pituitary GH levels by 200-fold in thyroidectomized rats--totally reversing the decrease produced by thyroidectomy; tamoxifen inhibited GH induction by T3 by 63%. The results indicate that estrogens powerfully induce pituitary GH in thyroidectomized but not intact rats through an estrogen receptor-mediated process. The DNA-binding domains of estrogen and T3 receptors, as well as their hormone response elements, share structural similarities. The present results are consistent with the hypothesis that estrogens and estrogen receptors may induce GH through unoccupied T3 response elements of the GH gene in thyroidectomized rats. PMID- 1915060 TI - A novel NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine-binding protein (CTBP; 5.1S) in rat liver: a comparison with 4.7S NADPH-dependent CTBP. AB - A novel NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) was purified by sequential fractionation of rat liver cytosol on Q Sepharose, phenyl-Sepharose, red-Sepharose, and polyacrylamide gel electrophoresis under nondenaturing conditions. The CTBP had a sedimentation coefficient of 5.1S, a Stokes' radius of 35 A, and a calculated mol wt of 76,000. The apparently homogenous protein consisted of a dimer of a polypeptide chain with a mol wt of 38,000 as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. NADPH increased both the affinity and maximal binding capacity for T3 in the 5.1S CTBP. The maximal activity to bind T3 was obtained by 3.0 x 10(-8) M NADPH. The calculated maximal affinity constant was 2.4 x 10(9) M-1, and the maximal binding capacity was 21,000 pmol T3/mg 5.1S CTBP. The order of affinity of iodothyronine analogs to the 5.1S CTBP was as follows: D-T3 greater than L-T3 greater than L-T4 greater than triiodothyroacetic acid. The optimal pH for T3 binding was 7.2-7.5. Ca2+, Mg2+, and Mn2+ (0.1-10 mM) did not influence T3 binding to CTBP. Zn2+ (1.0 mM), however, inhibited the binding. These results suggested that 5.1S NADPH-dependent CTBP, which is distinct from 4.7S CTBP that had been purified in our laboratory from rat kidney, is present in rat liver. PMID- 1915061 TI - Pulsatile luteinizing hormone responses to intermittent N-methyl-D,L-aspartate administration in hamsters exposed to long- and short-day photoperiods. AB - Hamsters exposed to short-day photoperiods (6-h light, 18-h darkness) develop a reversible inhibition of the reproductive axis which includes decreased LH pulse frequency, decreased FSH and testosterone levels, testicular regression, and presumably, decreased luteinizing hormone-releasing hormone (LHRH) release. The decrease in LHRH release could reflect a decrease in the ability of LHRH neurons to release the decapeptide in response to intermittent neuronal excitation. To analyze this possibility, the LHRH secretagogue, N-methyl-D-aspartate (NMA) was used to estimate relative releasability of endogenous LHRH pulses in hamsters exposed to long- and short-day photoperiods. Long-day (LD) or short-day (SD) hamsters were fitted with indwelling atrial catheters 2 days before experimentation. During 5-h sampling sessions (1300-1800 h), blood was withdrawn at 10-min intervals. In initial experiments, a NMA dose-response analysis revealed that 10 and 20 mg/kg NMA but not 2.5 and 5 mg/kg NMA, produced significant, dose-related LH responses in LD hamsters. Treatments with LHRH antagonist 4 h prior to NMA treatment completely blocked LH responses. The 10 mg/kg NMA dose was then used to directly compare LHRH responsiveness in LD and SD hamsters. NMA injections were administered to groups of LD and SD hamsters after hours 1, 2, 3, and 4 of sampling. In LD hamsters, LH responses to the first NMA pulse (2.65 +/- 0.09) were followed by diminishing responses to the second, third, and fourth NMA pulses (1.22 +/- 0.50, 1.22 +/- 0.43, and 1.15 +/- 0.42). By contrast, initial LH responses in SD hamsters (1.61 +/- 0.31) were followed by even more robust LH responses to the second, third, and fourth NMA challenges (2.89 +/- 0.34, 3.08 +/- 0.59, 2.65 +/- 0.32). Although LH responses to the first NMA pulse were slightly less in SD vs. LD animals, responses to all subsequent injections were actually greater in SD hamsters vs. their LD counterparts. Injections of 20 ng/kg LHRH in SD hamsters produced LH responses similar to those evoked by NMA. The same LHRH dose also produced continued, robust LH responses in LD hamsters, indicating that decrements in response to NMA were not due to diminished pituitary responsiveness. These results suggest that 1) the stimulatory actions of NMA are mediated by LHRH, 2) exposure to short days does not decrease the responsiveness of LHRH neurons to NMA, and 3) successive NMA challenges produce diminishing LH responses in LD hamsters, but not in SD hamsters.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915062 TI - Activin stabilizes follicle-stimulating hormone-beta messenger ribonucleic acid levels. AB - Activin, a gonadal peptide, stimulates FSH secretion in association with an increase in FSH beta messenger RNA (mRNA) levels at the level of the anterior pituitary gland. The goal of these studies was to determine whether the effects of recombinant human activin A (rhActivin A) are exerted at the post transcriptional level by affecting the stability of FSH beta mRNA. We determined the apparent half-life of FSH beta mRNA in the presence and absence of rhActivin A using actinomycin D. The anterior pituitary glands from adult male rats were isolated and dispersed enzymatically. Cells were preincubated in the presence of rhActivin A for 24 h to increase FSH beta mRNA levels. Actinomycin D was then added and the cells were incubated for a subsequent 4, 6, 8, 12, and 24 h in the presence or absence of rhActivin A. As reported earlier, the addition of rhActivin A caused parallel increases in FSH secretion and FSH beta mRNA levels, while having no effect on alpha or LH beta mRNA levels. Actinomycin D treatment decreased FSH beta mRNA to 49, 39, and 16% of control levels at the 4, 6, and 8 h time points, respectively. In contrast, when actinomycin D was added in the presence of rhActivin A FSH beta mRNA was reduced to 80, 58, and 42% of control levels at the 4, 6, and 8 h time points, respectively. Using the least squares method of analysis, the apparent half-lives of FSH beta mRNA under these two conditions were calculated. In the presence of actinomycin D, the half-life of FSH beta mRNA was 3.1 h. The addition of activin significantly increased the half life to 6.5 h. These results suggest that activin A stimulates FSH beta mRNA levels, at least in part, at the posttranscriptional level by increasing the stability of FSH beta mRNA. PMID- 1915063 TI - A monoclonal antibody to progesterone interrupts pregnancy in the hamster by curtailing secretion of the luteotropic complex of prolactin and follicle stimulating hormone. AB - A single ip injection of 6.5 nmol of a monoclonal (immunoglobulin G) antibody to progesterone (MAB-P4), administered on the morning of implantation (day 4), interrupted pregnancy by day 8 in 75% of treated hamsters. Pregnancy was unaffected until day 6 although histologically, the embryos contained very few mitotic figures. However, by day 7, the swellings began to regress and were completely eliminated by day 8. The onset of embryonic reabsorption coincides with a drastic fall in free (nonantibody-bound) serum progesterone (P4), in vitro production of P4, and in vitro and in vivo increases in estradiol. The effects of MAB-P4 are completely reversible by a concurrent injection of 1 mg P4 on day 4, whereas deferred injection of P4 to day 6 is ineffective. The onset of functional and structural luteolysis is paralleled by a significant decline in the minimal luteotropic complex of PRL and FSH but with no change in LH. The effects of MAB P4 are partially reversible by daily injection of FSH or PRL but not LH. We interpret these results as follows: normally during early pregnancy in the hamster endogenous P4 positively reinforces secretion of the luteotropic complex. MAB-P4 with its long half-life of 69 h binds serum P4 and therefore reduces circulating levels of free P4. Consequently, the secretion of PRL and FSH is curtailed without affecting LH. Thus, in the hamster when 6.5 nmol MAB-P4 is injected on day 4, the deprivation of P4 at the uterine level appears to be a secondary event to functional and structural luteolysis. PMID- 1915064 TI - The brain renin-angiotensin system and prolactin secretion in the male rat. AB - The present studies investigated the role of the brain renin-angiotensin system in the regulation of PRL secretion in the male rat. Blood samples were taken from conscious rats before, during, and after administration of test substances into the third cerebral ventricle. In the first series of experiments, we determined the sensitivity of the PRL response to intracerebroventricular (icv) administration of angiotensin II (Ang II) and found that PRL levels were significantly suppressed in a dose-related manner (10-500 ng). A dose of 1 ng did not significantly affect PRL values, compared to those from vehicle-injected animals. Ang II elicited water intake at doses of 50 and 500 ng, but not at the 10- or 1-ng doses. In the second series of experiments, we investigated the role of endogenous brain Ang II in the regulation of PRL secretion under basal and stimulated conditions. The endogenous system was manipulated by icv infusion of saralasin, an Ang II receptor antagonist, or icv injection of enalaprilat, a converting enzyme inhibitor, to prevent synthesis of Ang II. Neither saralasin nor enalaprilat administration produced an increase in PRL levels under basal, nonstressed conditions. However, during immobilization stress, when PRL levels increased 3-fold during icv vehicle infusion, saralasin infusion resulted in a 7 fold rise in plasma PRL titers relative to prestress baseline values. These results demonstrate that, in male rats, the inhibitory effects of icv administration of Ang II on PRL secretion are very sensitive and are observed at doses which do not affect water intake. The endogenous brain Ang II system appears not to be involved in the maintenance of the low plasma PRL levels observed under basal, nonstressed conditions. However, the system does appear to affect the magnitude of the PRL response to immobilization stress. PMID- 1915065 TI - A comparison of moment to moment and diurnal changes in circulating inhibin and testosterone concentrations in male rhesus monkeys (Macaca mulatta). AB - The secretion of inhibin by the testis was studied in the rhesus monkey, a species which exhibits marked episodic and diurnal patterns of testosterone (T) secretion. Inhibin and T were measured by RIA in blood samples drawn every 20 min for 24 h from 5 adult male monkeys. The molecular size of circulating inhibin, estimated by gel chromatography, was approximately 31 kDA. Plasma inhibin levels were undetectable in long term castrates. T was secreted episodically at a frequency of 6.0 +/- 0.9 pulses/24 h. The computer algorithm also identified 4.6 +/- 0.8 inhibin pulses/24 h. Of 30 T pulses among the 5 animals, however, only 7 coincided with low amplitude inhibin secretory bursts. Each animal demonstrated a significant diurnal periodicity in T secretion, with mean maximum concentrations at 0108 h (range, 2100-0640 h). By contrast, there was no significant diurnal rhythm for inhibin in any of the animals. The pulsatile administration of GnRH (0.1 micrograms/min, iv, for 3 min every 3 h) was used to activate the pituitary testicular axis in 6 juvenile monkeys. After 5 weeks of GnRH priming, a pulse of GnRH produced an immediate 4-fold rise in serum LH concentrations, followed within 30-50 min by a 5-fold increase in circulating T levels. FSH levels rose 50%. During the 3-h GnRH interpulse interval, however, there was no change in serum inhibin levels. Two GnRH-treated juvenile monkeys underwent bilateral orchidectomy. In each animal, circulating inhibin levels declined rapidly, with estimated first phase half-lives of 23 and 32 min, respectively. In conclusion, circulating inhibin concentrations in male rhesus monkeys exhibit neither the prominent moment to moment changes nor the circadian pattern characteristic of T secretion in this species. The relatively constant inhibin levels cannot be explained by prolonged metabolic clearance. The data are consistent with the proposal that most of the inhibin in the circulation is released across the apical surface of Sertoli cells into the seminiferous tubular fluid with passage into the rete testis from which it is continuously absorbed. The intermittent LH signal, by contrast, appears to make a minor contribution to the release of inhibin from the primate testis into the circulation. PMID- 1915066 TI - A carboxyl-terminal peptide from the parathyroid hormone-related protein inhibits bone resorption by osteoclasts. AB - PTH-related protein (PTHrP) interacts, via its amino-terminal 34 residues, with PTH receptors on osteoblasts to stimulate osteoclastic bone resorption indirectly. We now report that mature hPTHrP-(1-141) (EC50, approximately 10(-11) M) and a carboxyl-terminal fragment, PTHrP-(107-139) (EC50, approximately 10(-15) M), are potent inhibitors of resorption in an isolated rat osteoclast bone resorption assay, whereas hPTHrP-(1-108) and hPTHrP-(1-34) are inactive in this respect. PTHrP-(107-139) also inhibits resorption in a rat long bone organ culture system and reduces osteoclast spreading. PTHrP-(107-139) does not act on osteoclasts via a cAMP signal transduction mechanism, but its effects may be mediated by protein kinase-C. This previously unrecognized action of PTHrP, to inhibit osteoclastic bone resorption directly, indicates that PTHrP may be a precursor of multiple biologically active peptides with differing physiological functions. PMID- 1915067 TI - Human growth hormone variant produces insulin-like and lipolytic responses in rat adipose tissue. AB - Genes for normal human pituitary GH (hGH-N) and the GH variant (hGH-V) were expressed in stably transfected mouse mammary cells. The biological properties of hGH-N and hGH-V secreted into the medium were examined using rat adipocytes or epididymal fat segments. Methionyl-hGH produced in E. coli served as a reference standard. The three preparations were quite similar in their ability to bind specifically to intact fat cells and were virtually indistinguishable in their ability to increase glucose oxidation (an insulin-like response), induce refractoriness to insulin-like stimulation, and induce lipolysis in the presence of glucocorticoid. We conclude that placentally expressed hGH-V has a spectrum of metabolic activity comparable to pituitary hGH-N and may contribute to regulation of carbohydrate and lipid metabolism during pregnancy. PMID- 1915068 TI - Effect of antiserum to rat growth hormone (GH)-releasing factor on physiological GH secretion in the female rat. AB - To further study the physiological role of GH-releasing factor (GRF), we examined the effect of antiserum to rat hypothalamic GRF on spontaneous GH secretion in the normal female rat. Two groups of six conscious female rats were passively immunized with either nonimmune rabbit serum (NRS) or antirat GRF serum via a chronic indwelling atrial catheter. The secretory profiles of GH were observed by collecting blood samples at 15-min intervals for 1 h before and 4 h after administration. The NRS-treated rats showed a characteristic female pattern of spontaneous GH secretion. GH pulses were of low amplitude (mean +/- SEM, 26.8 +/- 2.4 ng/ml) and occurred irregularly at a frequency of 4.2 +/- 0.2/5 h, while interpeak through levels of GH were relatively high, with nadir values of 8.6 +/- 0.7 ng/ml. Synthetic rat GRF, given iv at a dose of 1 microgram/kg BW after the last blood sampling, stimulated GH release to a peak level of 153 +/- 37 ng/ml in the control rats. Administration of GRF antiserum caused a profound suppression of both pulse and trough components of GH secretion. This effect occurred rapidly, within 15 min after injection of antiserum, and GH secretion decreased uniformly to very low levels (3.4 +/- 0.1 ng/ml), with little or no fluctuation throughout the observation period. GRF antiserum also abolished the synthetic rat GRF-induced GH release, indicating sufficient potency of immunoneutralization. These results demonstrate that both GH pulses and troughs are dependent upon hypothalamic GRF in normal female rats, thereby substantiating earlier observations in male rats which demonstrated the physiological role of GRF in GH secretion. PMID- 1915070 TI - Coexpression of vasopressin and oxytocin in hypothalamic supraoptic neurons of lactating rats. AB - Magnocellular hypothalamic neurons in the rat supraoptic nucleus (SON) normally produce either vasopressin (VP) or oxytocin (OT). Here we demonstrate that many magnocellular neurons in the SON of lactating rats synthesize both hormones at the same time. We show the colocalization of the messenger (m) RNA that encodes the VP precursor with OT-neurophysin; OT mRNA with VP-neurophysin, the C-terminal glycopeptide of the VP precursor, and VP itself, and the presence of both mRNAs in the same cell. At the light microscopic level quantitative studies show that on the second day of lactation, 17% of the SON neurons produce both hormones, on the fifth day 13%, and on the ninth day 9%. Two days after lactation the number of cells that are positive for both hormones returns to the control level (2-3%). We also show by means of electron microscopic immunohistochemistry that both peptides (or their precursors) are present in the same neurosecretory vesicles in nerve endings in the posterior lobe of lactating rats. At the electron microscopic level quantitative studies show that on the second day of lactation 21% of the terminals contain mixed vesicles; this number increases to 24% by the fourth day and is down to 5% by the 15th day, a level similar to that found in control rats. Since the double-labeled cells seemed to be producing additional VP as opposed to OT, we hypothesized that the former should affect urinary osmolality. Urine samples of lactating rats show a significant (5-fold) increase in urine osmolality during lactation (highest on the second day). The increase in osmolality correlated with the increase in the number of VP positive cells during lactation. We suggest that magnocellular neurons that ordinarily synthesize little or no VP can produce this antidiuretic hormone to help the animal compensate for the loss of water associated with lactation. PMID- 1915069 TI - Circulating half-lives of follicle-stimulating hormone and luteinizing hormone in pituitary extracts and isoform fractions of ovariectomized and intact ewes. AB - Previous studies have shown that the circulating half-life (t 1/2) of serum FSH in ewes after hypophysectomy (HPX) increased 10-fold after ovariectomy (OVEX). The basis for this difference was examined in this study by determining the circulating half-life of serum FSH and LH in HPX ewes after administration of pituitary extracts and gonadotropin isoform fractions. High-speed supernatants of pituitaries from gonadal-intact and OVEX ewes were fractionated by electrofocusing in sucrose gradients and based on the pI distribution of FSH and LH divided into four pools, pH 4.3-4.8, 4.8-5.55, 5.8-6.7, and 6.7-10. These extracts were administered by iv bolus injection to HPX gonadal-intact ewes and blood samples collected between 15-1000 min later. The clearance pattern for both serum FSH and LH was heterogenous, indicative of a major rapid and a minor slow dissociating component. A significant (P less than 0.05) difference in circulating half-lives (rapid component) was observed between pituitary extracts from intact and OVEX ewes for FSH (t 1/2 = 32.8 +/- 8.6 min vs. 89.9 +/- 32.3 min) but not LH (31.3 +/- 9.2 min vs. 39.3 +/- 6.1 min, respectively), whereas no significant difference was observed between the corresponding FSH or LH isoform preparations. To establish if the difference in circulating half-lives obtained after HPX and bolus iv injection was due to mode of delivery, an extract of pituitaries from OVEX ewes was infused for 12 h into HPX sheep and the t 1/2 values determined after cessation of treatment and compared to those after a bolus injection. The clearance of both FSH and LH from plasma after infusion was significantly prolonged than after a bolus injection. It is concluded that the difference in circulating half-lives of FSH between pituitary extracts from intact and OVEX ewes after bolus administration is due to a difference in pituitary FSH composition. However, the prolonged clearance with infusion compared to bolus administration suggests that extrapituitary factors are also responsible. PMID- 1915071 TI - Human follicle-stimulating hormone exerts a stimulatory effect on spermatogenesis, testicular size, and serum inhibin levels in the gonadotropin releasing hormone antagonist-treated nonhuman primate (Macaca fascicularis). AB - The role of FSH in spermatogenesis was investigated in nonhuman primates depleted of testosterone by GnRH antagonist treatment. The GnRH antagonist antide (Nal Lys; [N-acetyl-D-2-naphthyl-Ala1,D-4-chloro-Phe2,D-pyridyl-Ala3, nicotinyl-Lys5,D nicotinyl-Lys6,isopropyl-Lys8,D-Ala10 ]-GnRH) was used at a daily dose of 450 micrograms/kg to suppress endogeneous gonadotropin and androgen production. Four groups of five cynomolgus monkeys (Macaca fascicularis) were subjected to the following treatment throughout a 16-week period: vehicle (group 1), GnRH antagonist (group 2), and GnRH antagonist plus human FSH (Fertinorm; 2 x 15 IU/day.animal; hFSH) during weeks 0-8 (group 3) or 8-16 (group 4). Testicular biopsies were performed before and after 4, 8, and 16 weeks of treatment. The tissue was analyzed by light microscopy and flow cytometry. Serum testosterone levels were suppressed into the range of orchidectomized animals in all GnRH antagonist-treated groups. In the absence of hFSH, serum inhibin levels were also markedly lowered. Concomitant administration of hFSH attenuated the GnRH antagonist-induced reduction of testicular size, while delayed treatment with hFSH failed to restimulate testicular volume. Numbers of A-dark spermatogonia, the reserve stem cells, were not altered by any of the treatments. hFSH either fully maintained or increased the counts for A-pale spermatogonia (renewing stem cells). The development of pachytene spermatocytes and round and elongated spermatids was markedly reduced or inhibited by the GnRH antagonist within 6-18 weeks. In contrasts, hFSH maintained these cell types at about 50% of baseline for 8 weeks. After 8 weeks of GnRH antagonist administration, hFSH stimulated A pale spermatogonia and spermatocytes 2- to 3-fold with only minor effects on spermatid numbers. By means of flow cytometry, testicular cells were quantified according to DNA content. Within 8-16 weeks of GnRH antagonist treatment the percentage of 4C (mainly primary spermatocytes), 1C (round spermatids), and 1CC cells (elongated spermatids) had fallen from 65-75% to 5-25%. hFSH completely maintained the relative number of these cells, but failed to significantly restimulate the formation of 1CC cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915072 TI - Functional recovery of the developing rat ovary after transplantation: contribution of the extrinsic innervation. AB - These experiments were undertaken to define the neuroendocrine mechanisms underlying the recovery of ovarian function after transplantation to an ectopic site. Both ovaries from 23-day-old rats were transplanted to the region of the neck, next to the jugular vein. Serum gonadotropin and plasma immunoreactive inhibin-alpha levels were determined at several intervals thereafter. Serum estradiol (E2) was measured during the first week posttransplantation. Reinnervation of the ovary by sympathetic and sensory nerves was monitored by immunohistochemistry. Sympathetic nerves were identified as adrenergic by the presence of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, and as peptidergic, by their neuropeptide-Y (NPY) or vasoactive intestinal peptide (VIP) immunoreactivity. Sensory nerves were identified by the presence of substance P (SP) and calcitonin-gene related peptide (CGRP) immunoreactivity. Serum LH and FSH increased, and plasma inhibin levels decreased, within 48 h after transplantation. Serum LH reached maximum levels on day 4, decreasing rapidly thereafter to basal values by day 6. These changes were functionally correlated with the posttransplantation fluctuations in serum E2, which decreased at 48 h, rebounded by day 4, and returned to basal values on day 7. Removal of the transplanted ovaries on day 3 resulted in the disappearance of serum E2 levels on day 4, thus confirming the ovarian graft as the source of E2. In contrast to LH, serum FSH remained significantly elevated for at least 3 weeks after transplantation, then decreased to basal levels after day 21, coinciding with the rise in inhibin secretion. Although a substantial loss of follicles was noted 48 h after transplantation, quantitative examination of the changes on day 4 revealed that approximately 40% of antral follicles were not necrotic. Ovulation and formation of corpora lutea were noted 21 days after transplantation. Reinnervation of the transplanted ovary by TH-, VIP-, NPY-, SP-, and CGRP-containing fibers was first detected 7 days after transplantation. Although VIP reinnervation was sparse and only transiently detected (days 7-21), the density of sympathetic (TH, NPY) and sensory (SP, CGRP) fibers increased 2- to 3-fold between days 7-28, remaining unchanged thereafter. Since apparent completion of this reinnervation coincided with reestablishment of normal levels of both LH and FSH, an additional experiment was performed to determine if the two events were causally related.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915073 TI - Expression of prolactin-related hormones in the early bovine conceptus, and potential for paracrine effect on the endometrium. AB - Hormones related to the pituitary hormones PRL and GH are produced by the utero placental unit of many species. In the cow, these include bovine placental lactogen (bPL) and a distantly related subfamily including the protein encoded by bovine PRL-related complementary DNA I (bPRCI). In the present studies, we defined the onset of expression of these genes in order to begin to study the regulation of their expression and function before implantation. Messenger RNA levels of both bPL and bPRCI were assessed by dot blot analysis of total RNAs prepared from conceptuses on days 15-25. Specific transcripts were not detectable at day 15 but were readily apparent beginning at day 17. To define the portions of the placenta responsible for expressing these genes, RNA was prepared from chorion (separated into cotyledons and intercotyledonary membrane), allantois, and amnion from day 58 gestation and analyzed by Northern hybridization. Transcripts for both these hormones were confined to the chorion, with intercotyledonary RNA containing at least as much as that prepared from cotyledons. To localize the product of these genes, extraembryonic membranes were immunostained with bPL and bPRCI antisera. Mononucleated trophoblastic cells stained for bPL and bPRCI at day 18; similar staining was apparent at days 23 and 24, as well as in some but not all binucleated cells. Microsomes prepared from endometrium exhibited specific binding of bPL throughout pregnancy as well as during the luteal phase of the cycle. At midgestation, these high affinity, low capacity receptors (dissociation constant of 1.27 x 10(-10) M, maximum binding capacity of 44.2 fmol/mg protein) demonstrated a selective affinity for bPL in preference to bGH and bPRL. Using this radioreceptor assay, we demonstrated the presence of bPL at nanomolar concentrations in washings from the uterine lumen, suggesting that bPL may exert paracrine effects on the endometrium. PMID- 1915074 TI - Age-related changes in proopiomelanocortin (POMC) gene expression in the periarcuate region of ovariectomized rats. AB - Aging of the female reproductive system results in a decline in estrous cyclicity which is due, in part, to alterations in hypothalamic function. Opioid peptides, especially the proopiomelanocortin (POMC)-derived neuropeptide, beta-endorphin, are thought to play a role in maintaining normal patterns of LH secretion. Previous studies have shown that the level of hypothalamic beta-endorphin and POMC messenger RNA (mRNA) decreases in old animals; however, it is unknown whether opioid peptides are involved in age-related reproductive decline. To determine whether POMC gene expression changes with age and is related to reproductive status, we assessed POMC mRNA levels by in situ hybridization histochemistry in the periarcuate region of young (3-4 months), middle-aged (10 12 months), and old (17-19 months) ovariectomized rats. Two methods of quantitation were used: 1) slides were apposed to x-ray film and POMC mRNA levels were quantitated over the entire periarcuate region, and 2) the same slides were dipped in emulsion and the level of POMC was quantitated in individual cells. POMC mRNA levels decreased 20-30% by the time animals were middle-aged, and no further decline was noted in the old animal groups. The decrease in POMC mRNA levels in the middle-aged and old animals occurred regardless of their reproductive status prior to ovariectomy. In addition, there was a 30-40% decline in the number of cells expressing POMC mRNA in middle-aged and old animals, suggesting an overall age-related decline in POMC gene expression in middle-aged and old animals independent of reproductive status. PMID- 1915075 TI - Glucose transport deficiency in diabetic animals is corrected by treatment with the oral antihyperglycemic agent pioglitazone. AB - Insulin-stimulated glucose uptake into muscle and fat involves regulation of the subcellular distribution and the expression of a specific facilitative glucose transporter protein (GLUT4). Peripheral glucose uptake is lowered in diabetes, and the expression of GLUT4 is depressed in animals that have been made diabetic (i.e. insulin deficient) by destruction of the pancreatic beta-cells. In the present study we found that GLUT4 expression is also decreased in an animal model for type II diabetes mellitus (noninsulin-dependent diabetes mellitus), KKAY obese mice. These KKAY mice have elevated circulating insulin levels, but target cell resistance to the metabolic actions of insulin. Treatment of both types of diabetic animals with pioglitazone, a new antihyperglycemic compound, corrects deficits in glucose transport and GLUT4 mRNA and protein abundance. Such corrections are, however, more readily detected in fat than in muscle. Increases in GLUT4 mRNA and protein levels and glucose transport function by pioglitazone are dependent upon the presence of circulating insulin. Treatment with pioglitazone alone is sufficient for correction of glucose transport in hyperinsulinemic insulin-resistant animals, but hypoinsulinemic animals require insulin therapy along with pioglitazone treatment for similar corrections. In these insulin-deficient animals, neither treatment with the drug alone nor minimal insulin replacement therapy results in substantial correction. Since insulin and this antihyperglycemic agent seem to work synergistically, it is likely that pioglitazone acts to amplify cellular responses to insulin. PMID- 1915077 TI - Expression of the low Km GLUT-1 glucose transporter is turned on in perivenous hepatocytes of insulin-deficient diabetic rats. AB - In normal fed rats the low Km glucose transporter GLUT-1 is expressed only in one row of hepatocytes immediately surrounding a terminal hepatic venule, while the high Km GLUT-2 is expressed in every hepatocyte. Previously, we showed that additional perivenous hepatocytes express GLUT-1 in fasting animals. In diabetes, as in starvation, the liver functions to release glucose into the circulation, but unlike starvation, circulating extracellular glucose is high in diabetes. By immunofluorescence and Western blotting we studied whether glucose or insulin is the primary extracellular signal for inducing GLUT-1 expression in hepatocytes. We observed that streptozocin-induced diabetes causes induction of GLUT-1 expression in the plasma membrane of hepatocytes within four cell rows of a terminal hepatic venule; GLUT-2 expression is unaltered. Chronic insulin treatment of diabetic rats reduces the number of rows of hepatocytes expressing GLUT-1 from approximately four to approximately two. In contrast, chronic insulin infusion into nondiabetic rats does not affect the number of hepatocytes expressing GLUT-1. Thus, both fasting and diabetes induce GLUT-1 expression in specific hepatocytes that normally do not express this gene. This induction correlates with low insulin levels in the blood, and not with circulating glucose levels. PMID- 1915076 TI - Stimulatory effects of recombinant follicle-stimulating hormone on Leydig cell function and spermatogenesis in immature hypophysectomized rats. AB - Although earlier reports suggest a stimulatory effect of FSH on Leydig cell function, controversy exists due to unavailability of FSH preparations free of contaminating LH. Recent availability of recombinant human FSH preparations made it possible to reinvestigate this question. Immature male rats were hypophysectomized (21-22 days old at surgery) and implanted with osmotic minipumps releasing 8 IU recombinant FSH or 18 IU purified human pituitary FSH (hpFSH)/day, whereas control animals received vehicle alone. After 7 days of treatment, testicular weight increased in the recombinant FSH and hpFSH-treated animals to values 2.3- and 2.5-fold those of controls, respectively. Analyses of the steroidogenic capacity of Leydig cells in testes of rats treated with recombinant FSH or hpFSH also revealed 2.9- and 3.8-fold androgen production in vitro compared to controls. In these rats recombinant FSH and hpFSH increased the LH receptor number in testicular homogenate by 50% and 70%, respectively. The increase in LH receptor number was associated with increases in the LH receptor mRNA levels. In hypophysectomized control rats, small seminiferous tubules contained spermatogonia and zygotene/early pachytene spermatocytes. In contrast, treatment with either FSH preparation enhanced the progression of meiosis, as evidenced by large number of pachytene spermatocytes and appearance of round spermatids. The present results show that LH-free recombinant FSH, like purified pituitary FSH, is capable of increasing the LH receptor content and steroidogenic responsiveness of Leydig cells through paracrine mechanisms together with a stimulatory effect on spermatogenesis. These observations suggest that prepubertal elevation of FSH secretion may be important for increasing Leydig cell steroidogenic capacity and spermatogenic progression. PMID- 1915078 TI - Hormonal control of the cervix in pregnant gilts. III. Relaxin's influence on cervical biochemical properties in ovariectomized hormone-treated pregnant gilts. AB - The effects of relaxin on the biochemical properties of both the uterine and vaginal portions of the cervix were examined between days 80-110 of pregnancy in ovariectomized gilts given progesterone to maintain pregnancy. In the cervix of control gilts and those ovariectomized and given progesterone plus relaxin, wet and dry weights, water content, and the glycosaminoglycan/collagen ratio increased between days 80-110 of gestation. Collagen concentrations based on wet or dry weight and glycosaminoglycan concentrations based on wet weight decreased during this period. After ovariectomy, there were no changes in these cervical connective tissue components when relaxin was not given. The glycosaminoglycans hyaluronic acid, heparan sulfate, and dermatan sulfate were found in the cervices of all treatment groups, with dermatan sulfate predominating. The ratio of the individual glycosaminoglycans did not change during pregnancy or with treatment. The major dermatan sulfate proteoglycan from the pig cervix was isolated and found to be similar in size, immunoreactivity, amino acid composition, and amino acid sequence to the major dermatan sulfate proteoglycans isolated from the cervices of other mammals. It is concluded that the relaxin-induced changes in the connective tissue composition of the cervix may contribute at least in part to increased extensibility and growth of the cervix during the last third of gestation in pigs. PMID- 1915079 TI - Precursors of alpha-inhibin modulate follicle-stimulating hormone receptor binding and biological activity. AB - Although several forms of monomeric alpha-inhibin have been isolated from follicular fluid, no biological function has yet been ascribed to these posttranslationally processed forms of the alpha-subunit precursor protein. Moreover, previous studies of a FSH receptor binding competitor (FRBC) isolated and characterized from porcine follicular fluid (pFF) suggested certain biochemical similarities between this protein and alpha-inhibin precursors. We, therefore, investigated the hypothesis that alpha-inhibin and/or its precursors might represent autocrine and/or paracrine modulators of FSH action in the ovary, accounting for some of this FRBC activity and thereby exerting some degree of regulation over follicular maturation. Three separate sources of alpha-inhibin proteins were investigated for FRBC activity, including pFF, human FF (hFF), and a 293 cell line into which the full-length human alpha-inhibin cDNA had been stably transfected. Conditioned medium from these transfected cells contained several forms of alpha-inhibin precursors as well as mature alpha-inhibin, but no beta-subunit or intact inhibin. alpha-Inhibin proteins from all three sources, purified by a variety of methods, including immunoaffinity chromatography on an anti-alpha-inhibin column, inhibited FSH binding to both natural tissue FSH receptors as well as recombinant rat FSH receptors expressed in 293 cells. Furthermore, dimeric inhibin and activin, medium from untransfected 293 cells, and non-alpha-inhibin-containing purification fractions were inactive in either assay. In addition, purified recombinant alpha-inhibin proteins were partial in vitro FSH antagonists in a bioassay in which cAMP generation from 293 cells expressing the recombinant FSH receptor is used as an index of FSH biological activity. These same fractions of hFF containing FRBC activity did not bind to LH receptors, thereby demonstrating receptor specificity for this activity. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting with alpha-inhibin or FRBC antisera, a 57,000 mol wt protein was identified in FRBC-active fractions from all three sources, suggesting that the active moiety was the full-length alpha-inhibin precursor protein or a large mol wt fragment, but not mature alpha-inhibin. Lastly, all FRBC activity from all three sources was extracted by an alpha-inhibin immunoaffinity column and was recoverable upon elution. These results demonstrate that proteins derived from the alpha-inhibin precursor modulate FSH binding to its receptor as well as its biological activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915080 TI - The mechanism of ICI 164,384 antiestrogenicity involves rapid loss of estrogen receptor in uterine tissue. AB - The antiestrogen ICI 164,384 (ICI) binds the estrogen receptor (ER) with approximately 20% the affinity of estradiol, but without the partial agonistic effects caused by tamoxifen. Investigations into the mechanism of ICI action have used ER molecules expressed in vitro to examine the binding of ER to ICI and the capacity of ICI-ER complexes to dimerize and bind to the estrogen response element (ERE). Our objectives were to study the biological effects, cellular distribution, and ERE-binding capacity of native uterine ICI-ER complexes after ip injection of 1 mg/kg ICI into 10-day castrate adult female mice. Synthesis of DNA and progesterone receptor were measured as end points of agonistic activity. ICI failed to stimulate either DNA or progesterone receptor synthesis above control levels, and pretreatment with ICI for 0.5 h reduced the stimulatory effect of estradiol by 75%. Measurement of uterine nuclear ER and cytosolic levels by exchange binding assay indicated a reduction in total ER levels within 0.5 h after ICI treatment, which remained below 20% for 24 h. Cycloheximide treatment did not block the ICI effect. Western blot analysis, immunohistochemistry, and steroid autoradiography confirmed the loss of ER protein. The ICI effect on ER was also demonstrable in vitro in the mouse TM4 estrogen-responsive cell line. ICI dramatically reduced ER levels to 5% of the control value by 4 h. Northern analysis indicated that ICI did not affect ER message levels, suggesting that the observed reduction in ER did not occur at the level of transcription. Gel shift assays indicated a low, but detectable, amount of ICI-ER binding to the vitellogenin A2 (VitA2) ERE. These results suggest that, although the ICI-ER complex binds weakly to DNA, ICI may cause its antagonistic effect by producing a rapid disappearance of the ER from the target tissue, resulting in an insufficient amount of ER to bind the native ligand and elicit agonist responses. PMID- 1915081 TI - Characterization of a N-bromoacetyl-L-thyroxine affinity-labeled 55-kilodalton protein as protein disulfide isomerase in cultured glial cells. AB - In glial cells, thyroid hormone regulates the polymerization state of the actin cytoskeleton by a mechanism that does not require protein synthesis or the nuclear T3 receptor. Using the affinity label N-bromoacetyl-L-T4, we identified a thyroid hormone-binding protein of 55 kDa (glial-p55) in cultured glial cells that is unique from the type II iodothyronine 5'-deiodinase and which exhibits a T4-dependent shift from a membrane-associated pool to the F-actin cytoskeleton. In a number of other cell types, a 55-kDa thyroid hormone-binding protein has been identified and shown to be a subunit of the enzyme protein disulfide isomerase (PDI). In this study we have characterized glial-p55 and compared it with purified rat hepatic PDI. Glial-p55 appears to be identical to PDI by peptide fragmentation analysis, using multiple methods. The hydrodynamic properties of glial-p55, determined by molecular sieve chromatography and sucrose density centrifugation, showed that this protein has a native molecular mass of 115 kDa, which is in close agreement with that reported for PDI. Like PDI, glial p55 is an acidic protein with a pI of 4.8 or less. Thus, the 55-kDa thyroid hormone-binding protein in glial cells appears to be PDI. PMID- 1915082 TI - Mammary stroma modulates hormonal responsiveness of mammary epithelium in vivo in the mouse. AB - Several lines of evidence indicate that there may be important stromal influences on epithelial behavior in a number of adult organs. The present studies were undertaken to examine the contribution of mammary gland stroma to mammary epithelial cell hormonal responsiveness in vivo. To accomplish this, mouse mammary epithelium from a developmental state that is not responsive to estrogen (E)-regulation of progesterone receptors (3-week-old) was surgically recombined with mammary stroma from a developmental state that is E-responsive (10-week-old) and vice versa. The recombinants were then tested in vivo for the ability of E to regulate epithelial progesterone receptors. The results demonstrate that when immature nonresponsive epithelium is transplanted to mature stroma of E responsive mice, the epithelium prematurely acquires E responsiveness. When the converse experiment was carried out, mature E-responsive epithelium retained its responsiveness when transplanted to stroma of immature nonresponsive mice. The contribution of the host systemic milieu to changes observed upon transplantation was also assessed. To do this, mature stroma was transplanted to nonresponsive mice before transplantation with nonresponsive epithelium. Under these conditions, the mature stroma was still able to promote responsiveness. Analysis of mammary gland morphology of the surgical recombinants revealed no significant differences in epithelial structures or organization that could account for the observed differences in hormone responsiveness. From these results we conclude that the local environment of mammary stroma has the capacity to influence mammary epithelial cell behavior and can modulate epithelial hormonal responsiveness in vivo. The mechanisms underlying stromal influences on epithelial behavior remain to be elucidated. PMID- 1915083 TI - Metabolic interfaces between growth and reproduction. IV. Chronic pulsatile administration of growth hormone and the timing of puberty in the female sheep. AB - Puberty in the female lamb is accompanied by an increased frequency of LH pulses, and during normal development this is preceded by a decline in GH. Conversely, in the growth-retarded lamb, when LH levels are depressed by low nutrition, GH secretion is elevated. Based upon this inverse relationship, we tested the hypothesis that GH may act as a metabolic signal from the brain to inhibit the secretion of LH, and that the decline in GH times puberty. Our approach was to extend high circulating GH levels far beyond the early postnatal period, in a physiological pattern and level, in an attempt to block the pubertal LH rise. To evaluate the pattern of LH as a continuous variable under conditions of constant estradiol negative feedback, the gonadotropin was measured in blood samples collected by jugular venipuncture twice weekly; the lambs were ovariectomized and treated chronically with estradiol (Silastic capsule) beginning at 3 weeks of age. Nine lambs served as untreated controls, and 7 were infused iv with pituitary-derived bovine GH (bGH) between 5 and 28 weeks of age. A programmable backpack infusion pump delivered bGH as hourly pulses, with a total dose of 18 micrograms/kg.24 h, to maintain a physiological pattern and level of GH. At various ages, blood samples were collected at 12-min intervals for 6 h to monitor patterns and levels of peripheral LH and GH. Circulating GH in untreated and treated lambs averaged 7.7 +/- 1.5 ng/ml over a 6-h period at 4 weeks of age and declined to 1.1 +/- 0.2 ng/ml by 19 weeks in the untreated lambs; in contrast, bGH-infused lambs averaged 10.4 +/- 0.9 ng/ml at 19 weeks. Although body weights did not differ, back fat depth and quantity of perirenal fat were reduced in bGH treated females compared to that in controls. Moreover, insulin-like growth factor-I levels were higher in bGH-treated compared with control lambs, and the bGH-treated lambs exhibited glucose intolerance, thus confirming that infused bGH was biologically active. Neuroendocrine sexual maturity, however, was not different in bGH-treated and control lambs, and it occurred at 21-22 weeks of age. The results do not support our hypothesis that decreasing GH secretion is a requirement for puberty in the sheep. Moreover, unlike in children with delayed puberty, exogenous bGH did not advance normal puberty in the lamb.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915084 TI - Multiple steroidogenic cell populations in the thecal layer of preovulatory follicles of the chicken ovary. AB - The thecal layer of the preovulatory follicle of the chicken ovary produces primarily androgens and estrogens. However, the precise cellular sites of androgen and estrogen synthesis in the thecal layer have not been identified. Therefore, our aims were 1) to identify steroidogenic cells in the thecal layer of the preovulatory follicles by localizing specific steroidogenic enzymes in these cells by immunocytochemistry, and 2) to confirm that these cells which contained the specific steroidogenic enzymes secreted the expected steroid in a short term cell incubation. Follicles were collected 2 h after oviposition and prepared for immunocytochemistry and short term cell incubation. Immunocytochemistry for cholesterol side-chain cleavage cytochrome P450 (P450SCC), 17 alpha-hydroxylase cytochrome P450 (P450C17), and aromatase cytochrome P450 (P450AROM) was performed to localize pregnenolone-, androgen-, and estrogen-producing cells, respectively, on frozen sections and paraffin sections of the five largest preovulatory follicles. Interstitial cells showed immunoreactivity for both P450SCC and P450C17, whereas a specific cell population of the theca externa, hereafter termed aromatase cells, showed immunoreactivity for P450AROM. Furthermore, fibroblasts in the theca externa indicated immunoreactivity for P450C17. The immunoreactivity of P450C17 and P450AROM enzymes in specific cells in the theca externa appeared to decrease with follicular maturation. The third largest, fourth largest, and fifth largest follicles were selected for short term cell incubations because the immunoreactivity for P450 enzymes in the thecal layer of these follicles was high. Isolated theca interna cells, theca externa cells, and a combination of interna and externa cells were incubated with/without ovine LH (oLH) for 3 h. The medium was assayed for progesterone, testosterone, and 17 beta-estradiol by RIAs. Incubation of theca interna cells with oLH increased progesterone and testosterone production in a dose-dependent manner. However, we did not observe any production of progesterone and testosterone by theca externa cells. Theca externa cells produced 17 beta-estradiol, and its production was increased significantly when theca interna and externa cells were coincubated in the present of oLH. Based on these data, we propose a multiple cell theory for steroidogenesis in the thecal layer of preovulatory follicles of the chicken ovary which states that interstitial cells in the theca interna produce progestins and androgens, fibroblasts in the theca externa may function as an additional site for the conversion of progestins to androgens, and aromatase cells in the theca externa require androgens as substrate to produce estrogens. PMID- 1915086 TI - Nomenclature clarification for the bovine placental prolactin-related hormones. PMID- 1915085 TI - Transforming growth factor-alpha and -beta differentially regulate growth and steroidogenesis of bovine thecal cells during antral follicle development. AB - The actions and interactions of transforming growth factor-alpha (TGF alpha) and TGF beta on growth and differentiation of bovine thecal cells were investigated. Bovine thecal interna cells were isolated from small (less than 5 mm), medium (5 10 mm), and large (greater than 10 mm) antral follicles and cultured in the presence or absence of TGF alpha and/or TGF beta. Both [3H]thymidine incorporation and changes in cell number (i.e. DNA levels) were evaluated to determine effects on thecal cell growth. Short term treatment of cells with TGF alpha (18-24 h) stimulated thymidine incorporation, and longer term treatments (4 days) increased cell number. TGF beta suppressed thymidine incorporation below that observed in untreated cultures, but had no effect on cell number. When combined with TGF alpha, TGF beta suppressed the ability of TGF alpha to stimulate thymidine incorporation and increase cell number. The response to these growth factors was similar for cells isolated from the different stages of antral follicle development. The effects of TGF alpha and TGF beta on thecal cell differentiation were evaluated by quantitating changes in androstenedione and progesterone accumulation in cultures treated with TGFs in the absence (basal) or presence of hCG, estradiol (E2), or a combination of hCG and E2. E2 and hCG were included in this study because previous research has demonstrated that these hormones alter thecal cell steroidogenesis. Treatment with TGF alpha resulted in a suppression of basal and hormonally stimulated accumulation of androstenedione during days 0-3 of culture, whereas TGF beta did not significantly alter androstenedione accumulation. TGF alpha also suppressed progesterone accumulation during days 0-3 of culture in the absence or presence of hormones. In contrast, TGF beta stimulated accumulation of progesterone in cultures that did not contain E2, which suppressed progesterone during this period. Therefore, during days 0-3 of culture, TGF alpha appears to have suppressive effects on androstenedione and progesterone production, whereas TGF beta can stimulate progesterone production in the absence of E2. During days 3-6 of culture, thecal cell differentiation changes, and the capacity to produce androstenedione dramatically declines, while the capacity to produce progesterone increases. During this period, either TGF alpha or TGF beta slightly increased basal progesterone accumulation and partially suppressed the ability of hCG to stimulate progesterone. The effects of TGFs on thecal cell steroidogenesis were similar with cells isolated from the different stages of antral follicle development. Results from these studies provide evidence that THF alpha and TGF beta can modulate thecal cell growth and differentiation (i.e. steroidogenesis).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915087 TI - Distribution of circulating insulin-like growth factor-I (IGF-I) into tissues. AB - Intravenous infusions of amino terminal methionyl insulin-like growth factor-I (N Met IGF-I; 8 micrograms/kg body wt x h; 24 h) were performed in lactating sheep and samples of mammary lymph, cerebrospinal fluid, and postinfusion tissues collected to examine distribution of the recombinant analog outside the vascular space. Samples were analyzed using an antibody specific for N-Met IGF-I and a second IGF-I antibody which recognized endogenous IGF-I and the N-Met variant equally. N-Met IGF-I infusion increased total plasma IGF-I immunoreactivity (ir) from 150 to 290 ng/ml. N-Met IGF-I was distributed into mammary lymph, increasing total lymph IGF-I from 60 to 130 ng/ml. By contrast iv N-Met IGF-I had no significant effect on IGF-I ir in cerebrospinal fluid. N-Met IGF-I was distributed on plasma and lymph IGF binding protein as endogenous IGF-I with binding to the 150,000 mol wt species predominant in plasma and the 40,000-50,000 mol wt pool of proteins predominant in lymph. N-Met IGF-I was also distributed into extra-vascular tissue accounting for 36% (kidney) to 62% (spleen) of total tissue IGF-I ir at the end of the infusion. The IGF-I antibodies were also used for the autoradiographical localization of IGF-I in postinfusion muscle and mammary tissue. No significant difference in antibody binding was observed to muscle fiber and mammary epithelium, but in marked contrast binding of the N-Met specific antibody to connective tissue of muscle and mammary was significantly less than the total IGF-I antibody (P less than 0.001; N-Met/total, 0.12). The data suggest that the contribution of blood-derived N-Met to total IGF-I varies markedly between tissues and provides evidence that blood-borne IGF-I may fill specific endocrine functions in selected tissues. PMID- 1915088 TI - Progesterone regulates epidermal growth factor receptor on mucous secreting cells in the rabbit endocervix. AB - During postnatal differentiation, epidermal growth factor (EGF) receptor is expressed by all major cell types of the cervix. Computer-assisted image analysis confirmed the highest concentration of EGF receptor is in the epithelial cells. Flow cytometric analysis of subpopulations of epithelial cells from estrous rabbits showed the mucous secreting cells had the highest concentration of EGF receptor, i.e. 1-1.5 x 10(5) receptors per cell. Because the mucous secreting cells are targets for steroid hormones it seemed likely that steroids regulate EGF receptor expression. To investigate this possibility, hormone-dependent changes in EGF receptor expression were quantified by flow cytometry. Ovariectomy and the treatment of ovariectomized animals with estradiol altered forward angle light scatter and side scatter signals which correlated with cell size and secretory granule content, respectively. However, the number of epithelial cells and the number of EGF receptors per cell were unaffected. Progesterone treatment of ovariectomized animals dramatically reduced the number of EGF receptors on the mucous secreting cells, accounting for a 43% reduction in the total EGF receptor content of the epithelium. The treatment of neonates with diethylstilbestrol did not change the number of EGF receptors in endocervical epithelial cells when examined in adulthood. However, the number of mucous secreting cells was decreased, thereby reducing the EGF receptor content of the epithelium 19-36% compared to estrous and estradiol-treated animals. These results provide the first evidence that progesterone regulates EGF receptor on mucous secreting cells in the endocervix and that diethylstilbestrol treatment alters the EGF receptor content of the epithelium by altering its cellular composition. PMID- 1915089 TI - Distribution and characterization of endogenous benzodiazepine receptor ligand (endozepine)-like peptides in the rat gastrointestinal tract. AB - Endozepine is the generic name for a family of peptides that are capable of displacing benzodiazepines and the 3-carboxylate ester of beta-carboline from their specific binding sites on synaptosomal membranes. The 104-amino acid polypeptide diazepam-binding inhibitor (DBI) and the octadecaneuropeptide (ODN) generated by tryptic digestion of DBI are two members of the endozepine family. In the present study we have used RIA, HPLC, in situ hybridization, and immunohistochemical techniques to identify and localize endozepine-like molecules in the rat gastrointestinal tract. Significant amounts of endozepine-like immunoreactivity (LI) were detected throughout the gut; the highest concentrations were found in the duodenum and antrum. HPLC analysis revealed that the immunoreactive material eluted as a major peak with a higher retention time than that of synthetic ODN. The distribution of the immunoreactive peptide(s) was studied using the peroxidase-antiperoxidase technique at the light microscope level. Endozepine-LI was localized only in the epithelial cell layer of the intestine in both goblet cells and enterocytes. In the stomach, endozepine-LI appeared to be restricted to deep layer of the epithelial cells. The diffuse neuroendocrine cells (amine precursor uptake and decarboxylation system) as well as myenteric and neuronal cells were devoid of immunoreactivity. A good correlation was observed between RIA and immunocytochemical data, in that the esophagus, which contained very low concentrations of endozepine-LI, also exhibited weak immunostaining of secretory cells. In situ hybridization using a 35S-labeled cRNA probe showed that endozepine mRNA was located in the mucosa. Taken together, these results show that in the rat, epithelial cells synthesize endozepine-LI material. Since epithelial cells also contain a high density of peripheral-type benzodiazepine-binding sites, our data indicate that endozepines may play a role in water, electrolyte, and/or mucus regulation in the rat gastrointestinal tract. The occurrence of high levels of endozepine-LI in the rat stomach also suggests that endozepines can be involved in the regulation of gastric acid secretion through modulation of local gamma-aminobutyric acid-ergic neurotransmission. PMID- 1915090 TI - Estrogen action on growth hormone in pituitary cell cultures from adult and juvenile macaques. AB - Basal growth hormone (GH) levels are higher in female than male primates, and estradiol (E) treatment of gonadectomized primates increases serum GH. To determine if the effect of E is mediated at the level of the somatotroph, we verified the effect of E-treatment on serum GH in spayed macaques, and then examined the effect of E on GH secretion in serum-free monkey pituitary cultures. Daily blood samples were obtained from cynomolgus macaques which were spayed upon detection of menstruation and immediately implanted with either empty (n = 5) or E-filled (n = 5) 2-cm silastic capsules. The average level of GH was significantly higher (P less than 0.003) in the E-treated group than in the control group (6.4 +/- 0.7 vs. 3.7 +/- 0.6 ng/ml). Pituitaries from rhesus monkeys were dispersed and cultured in 48-well plates on extracellular matrix in DME/F12 with insulin, transferrin, selenium. Using pituitary cells from a long term spayed female, two plates were established with and without phenol red. Each plate was treated with E in a dose-related manner (0.001-10 nM) from days 0-18 (4 wells per dose). There was a significant dose-related increase in medium prolactin (PRL) in both plates, but E had no effect on GH. Therefore, the effect of E on GH in spayed monkeys cannot be accounted for by a direct action on somatotrophs. Additional phenol red-free pituitary cultures were established from four juvenile males, one adult male, two juvenile females, and two adult females and treated with E in a dose-related fashion for 28 days. Neither the adult male, the adult female, nor the juvenile female cultures exhibited an increase in GH with E treatment. Only the four juvenile male pituitary cultures showed a variable increase in GH with maximal responses ranging from 5 to 40% over control. This data suggested that the juvenile male pituitary contained an E sensitive GH-secreting cell population which is not present in the other pituitary cultures. PRL and GH double-immunocytochemical staining of pituitary cultures from an adult female and a juvenile male revealed a significant population of rounded and possibly double-labeled cells in the juvenile male culture which were infrequently seen in the adult female culture. Speculatively, this population could represent mammosomatotroph stem cells that corelease GH and PRL upon stimulation. PMID- 1915091 TI - Endometrial relaxin: effects of mastectomy in the cyclic and pregnant guinea pig. AB - Mastectomy in the guinea pig increases the incidence of still births and neonatal deaths compared with intact animals. The guinea pig has the endometrial gland cells (EGC) as the major source of relaxin, and this hormone has possible roles in uterine quiescence, cervical dilatation, and lengthening of the interpubic ligament in pregnancy. An effect of mastectomy on uterine relaxin has been sought by immunocytochemical localization during the estrous cycle, mid and late pregnancy and on endometrial relaxin gene expression in the late pregnant mastectomized animal by Northern analysis. Endometrium from midpregnant (day 35) and late pregnant (day 63) and from lactating (days 5, 21, and 28) guinea pigs immunostained with antiserum to porcine relaxin by the avidinbiotin technique. By increasing the sensitivity of the latter, relaxin immunostaining was also detected for the first time in EGC from cyclic animals (days 9 and 14). A pattern and intensity of relaxin immunostaining could be readily assigned to each of the stages examined: estrous cycle, midpregnancy, late pregnancy, lactation, and post weaning. The dark uniform staining of the EGC in late pregnancy was followed by sporadic staining of the EGC in lactation, returning to the cyclic picture after weaning. Endometrium from mastectomized cyclic and late pregnant guinea pigs showed a reduction in the amount of immunostaining compared with the relevant control animals. The reduction was most pronounced in the mastectomized late pregnant guinea pig. This result was reflected in an apparently lower level of relaxin mRNA in the endometrium of these animals compared to intact controls. These data indicate a novel linkage between the mammary gland, either directly or indirectly, to the nonpregnant or pregnant uterus. The loss of this signal appears to be associated with subsequent problems at parturition which may be linked to the reduction in endometrial gland relaxin production. The nature of this signal from the mammary gland, normally considered to be an exocrine rather than an endocrine gland, is unknown. PMID- 1915092 TI - Growth hormone-releasing factor stimulates calcium entry in the GH3 pituitary cell line. AB - The GH3 pituitary cell line has been extensively used to study various aspects of the stimulus secretion coupling process. It is known that GH3 cells release PRL and GH in the basal state and in response to various secretagogues. However, this cell line was considered unsuitable as a model for studying the effects of GHRF since the neuropeptide did not affect GH secretion or gene expression. This suggested that the GH3 cells may lack GHRF receptors. The present study investigates the effect of GHRF on free intracellular Ca2+ concentrations in GH3 cells. Cytosolic free calcium concentrations ([Ca2+]i) were monitored in individual cells by microspectrofluorimetry using the fluorescent dye indo 1. When the cells were challenged with a brief application of GHRF (100 nM; 15 sec), 36 out of 59 of these cells responded within a few seconds by a marked increase in [Ca2+]i. GHRF enhanced the frequency of [Ca2+]i oscillations in spontaneously active cells or triggered [Ca2+]i oscillations in inactive cells. The response to GHRF was totally blocked by external Ca2+ free solutions and Ca2+ channel blockers. Combined electrophysiological and fluorescent experiments were carried out in 16 cells. Eleven responded to GHRF. In all cases, the Ca2+ transients triggered by GHRF were associated with action potentials. The Ca2+ responses observed in our experiments clearly show that GH3 cells possess membrane receptors to GHRF. Thus, it is likely that the lack of secretory response observed in GH3 cells does not result from the absence of binding sites to the peptide. It is more likely to be related to alterations of transduction mechanisms resulting in uncoupling between stimulation and secretion. PMID- 1915093 TI - The role of Ca(2+)-related events in glucose-stimulated desensitization of insulin secretion. AB - The spontaneous decline of insulin secretion (third phase) that occurs under a variety of secretory conditions is well documented and suggests a general impairment or desensitization of the secretory process. We have examined several aspects of Ca2+ flux as well as regulators of Ca-linked second messenger events in freshly isolated rat islets chronically stimulated with glucose over 24 h, a period that encompasses initial (hour 1), peak (hour 3), and subsequent impaired or desensitized (hour 20-22) secretion. In islets incubated for these periods in HB104 medium with 22 mM glucose, 45Ca2+ uptake did not vary (12.6 +/- 1.6 vs. 10.2 +/- 1.7 vs. 13.2 +/- 3.4 pmol Ca2+/islet.10 min at 1, 3, and 22 h, respectively). Chronic incubation in 2 mM glucose reduced total Ca2+ uptake at each of the time periods, but, again, uptake did not change with desensitization (9.8 +/- 1.4 vs. 6.6 +/- 2.1 vs. 7.8 +/- 2.3 pmol Ca2+/islet.10 min). In 11 mM glucose, the Ca channel antagonist verapamil (1-10 microM) reduced insulin secretion by 55-80% in a dose-dependent manner over 1-3 h; islets continuously exposed to verapamil escaped inhibition by 20 h even at the highest concentration. However, in islets first exposed to 10 microM verapamil only during 20-22 h, hourly insulin secretion was suppressed 25%, 45%, and 33% at 20, 21, and 22 h, respectively, indicating that glucose-desensitized islets were still sensitive to further inhibition of Ca channels. Staurosporine (1 microM), an inhibitor of protein kinase-C activity, progressively inhibited glucose stimulated insulin secretion from 48% at 1 h to more than 80% by 3 h; again, this inhibitory effect was lost by 20 h of chronic staurosporine. When staurosporine was first administered at 20 h, insulin secretion was modestly suppressed and returned to control values in the next hour. With continuous glucose, the islet response to positive stimulation of endogenous C-kinase activity by carbachol was maintained. The Ca/calmodulin inhibitor trifluoroperazine also inhibited insulin secretion by 75-80% during 1-3 h and continued to exert inhibitory effects through 23 h of continuous administration. We conclude that even though insulin secretion has desensitized to glucose, 1) Ca2+ entry is unchanged and is still regulated by glucose, 2) voltage-dependent Ca channels are still sensitive to blockade by acute verapamil, but can desensitize to chronic verapamil; 3) stimulus-enhanced C-kinase activity may be especially labile during glucose induced desensitization, while 4) possible Ca/calmodulin potentiation of secretion persists through the three secretory phases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915094 TI - Evidence for an organ- and sex-specific role of basic fibroblast growth factor in the development of the fetal mammalian reproductive tract. AB - Basic fibroblast growth factor (bFGF) has been implicated as an embryonic mesoderm-inducing factor. It has also been detected in the mesodermally derived fetal and adult reproductive tracts. To address its possible role in the development of the reproductive tract, male and female fetal genital ridges and urogenital (UG) sinuses were transplanted bilaterally under the kidney capsule of syngeneic host rats; the transplants and the hosts were the same sex. Antiserum to bFGF (anti-bFGF) or normal rabbit serum (NRS) was infused into the right renal artery. The transplants on the left uninfused kidney served as internal controls. Upon vascularization, the transplants grow and differentiate essentially normally, but their overall growth after 14 days was reduced by about 40% compared to their growth in situ. Neutralization of endogenous bFGF with anti bFGF resulted in approximately 41% inhibition of growth in the male genital ridge, but had no effect on the male UG sinus or any component of the female reproductive tract. The growth suppression of the male genital ridge was accompanied by an inhibition of the differentiation of the epididymis. After 7 days of treatment, development of the epididymis was impaired by 75%, and by 14 days, the organ was absent. Previous studies of fetal reproductive tract development have focused on the role of steroids and Mullerian inhibiting hormone. Our studies suggest that bFGF plays a role in the development of the male reproductive tract, especially the epididymis, and further suggest the possible role of this peptide growth factor in a steroid hormone-dependent process. PMID- 1915095 TI - Effect of recombinant human inhibin on gonadotropin secretion by the male rat. AB - We have examined the effect of recombinant human inhibin-A on basal and GnRH induced gonadotropin secretion by male rats or cultured anterior pituitary cells. Inhibin, administered sc 6 h before the experiment, induced dose- and time related decreases in plasma FSH, but not LH, levels in both intact and castrated male rats. Inhibin also significantly interfered with the in vivo stimulatory effect of 20-500 ng GnRH on FSH release, but had inconsistent and usually modest effects on the LH response. While exposure of cultured pituitary cells to inhibin for 72 h has been reported to interfere with GnRH-induced gonadotropin release, we examined here the effects of shorter exposure periods relevant to in vivo experiments. Exposure of the cells to inhibin (31.3-312.5 pM) for 2-6 h measurably (P less than or equal to 0.01) decreased the ability of 10 nM GnRH to stimulate both FSH and LH released by cultured cells. In contrast, lower (3.1 and 9.4 pM) doses of inhibin had little or no effect. Longer exposures to inhibin (10, 24, and 72 h) increased the inhibitory effect of 31.3-312.5 pM inhibin, while 3.1 and 9.4 pM remained ineffective at all times. These results indicate that exposure of the male rat to inhibin for 6 h decreases FSH secretion, and that this effect is at least partially mediated through blunting of the pituitary response to GnRH. In contrast, the ability of inhibin to interfere with LH release, which is readily apparent in cultured pituitary cells, appears to be of lesser importance in the intact male rat. PMID- 1915097 TI - Hormonal regulation of type II glucocorticoid receptor messenger ribonucleic acid in rat brain. AB - Differences in the regulation of type II glucocorticoid receptor (GR) mRNA levels in female rat brain regions involved in the control of the hypothalamic-pituitary adrenal axis were studied by Northern blot analysis after chronic administration of corticosterone or dexamethasone to adrenalectomized (ADX), ovariectomized (OVX), and ADX/OVX animals. The effect of chronic estradiol or progesterone treatment of intact animals was also studied. Our results show that type II GR mRNA levels of ADX animals were significantly increased above control values in amygdala (140%) and hippocampus (196%), but not in hypothalamus. These increased transcript levels were down-regulated by corticosterone or dexamethasone, with the exception of those in the amygdala, where corticosterone had no effect. Ovariectomy significantly increased hypothalamic GR mRNA content (174%) over control values, and this increase was sensitive to dexamethasone. The combined effect of adrenalectomy/ovariectomy on GR mRNA levels was greater than that of adrenalectomy only in amygdala. Corticosterone increased amygdala transcript levels in OVX and ADX/OVX animals. Estradiol administration to intact animals raised the GR mRNA content of amygdala, while progesterone treatment had no effect on any of the brain regions studied. We conclude that there exists heterogeneity with respect to type II GR mRNA regulation by corticosterone and dexamethasone in brain regions of ADX female rats, and that certain limbic structures show greater sensitivity to these hormonal manipulations, suggesting a more prominent role in the regulation of the hypothalamic-pituitary-adrenal axis. Our results also suggest that circulating estrogens can influence the sensitivity of brain structures (i.e. hypothalamus and amygdala) to glucocorticoids by altering GR mRNA levels. These regions may represent integration sites at which gonadal steroids are able to alter stress hormone secretion. PMID- 1915096 TI - Effect of recombinant inhibin on follicle-stimulating hormone secretion by the female rat: interaction with a gonadotropin-releasing hormone antagonist and estrogen. AB - There is considerable support for the hypothesis that one component of FSH secretion is independent of GnRH. The ability of follicular fluid preparations containing inhibin to suppress FSH release in the absence of GnRH drive has suggested that this component might be responsive to gonadal proteins. However, follicular fluid contains several proteins that either stimulate or inhibit FSH secretion, thus complicating interpretation of the results. The recent availability of recombinant human (rh) inhibin-A has allowed us to specifically investigate the effect of this protein on FSH secretion by rats whose GnRH release and/or effect was blocked by a specific antagonist, [Ac-D2Nal1,DCpa2, D3Pa13,Arg5, D5-(p-methoxyphenyl) 5-oxo-2-aminopentanoic acid16, DAla10]GnRH, or by estradiol (E2). In a first experiment, the GnRH antagonist (100 micrograms/kg, injected sc 21 h earlier) lowered plasma immunoactive FSH levels by 36%, and rh inhibin-A (25 micrograms/kg, injected iv 6 h earlier) lowered them by 44%. The combination of both treatments decreased FSH values by 82% (P less than or equal to 0.01 vs. either compound alone). Inhibin and the antagonist also significantly (P less than or equal to 0.01) decreased FSH bioactivity. A second experiment investigated the independent or combined effects of inhibin and E2. E2 (40 micrograms/kg, injected sc at -36 and -12 h) lowered FSH levels by 53%, and inhibin (25 micrograms/kg, injected iv at -6 h) decreased FSH concentrations by 37%. Administration of both compounds produced a 63% inhibition (P less than or equal to 0.05 vs. inhibin alone; P less than or 0.01 vs. E2 alone). Finally, we studied the interaction among the GnRH antagonist, inhibin, and E2. In this protocol plasma FSH levels in rats injected with inhibin and the antagonist did not show an additional decrease after treatment with E2. These results indicate that plasma FSH levels in rats whose GnRH receptors or secretion are blocked can be further lowered by inhibin. Thus, the ability of rh-inhibin-A to interfere with FSH secretion in the ovariectomized rat appears to involve a mechanism independent of the GnRH drive. PMID- 1915098 TI - Effect of extracellular sodium on thyroid hormone uptake by mouse thymocytes. AB - In mouse thymocytes, a stereospecific saturable energy-dependent and ouabain inhibitable system facilitates T3, but not T4, entry. We studied here the effect of sodium depletion on cellular uptake of thyroid hormones by mouse thymocytes. Time-course experiments indicated that extracellular sodium depletion reduced [125I]T3 uptake at each time studied. At equilibrium, the removal of extracellular sodium and its substitution with isoosmotic choline decreased saturable [125I]T3 uptake by 60 +/- 10%; this effect was dose dependent. The substitution of sodium with lithium, instead of choline, had no effect on the uptake process. [125I]T4 uptake was lower than that of [125I]T3 and not affected by sodium depletion. The half-maximal effect of sodium deprivation on [125I]T3 uptake was reached at an extracellular sodium concentration of about 40 mM. The variation of external pH influenced T3 accumulation by thymocytes. [125I]T3 progressively decreased from acid to alkaline pH under normal and sodium-depleted conditions; however, the sodium-dependent fraction was more than doubled at physiological pH compared to that at more acidic and more alkaline pH. The sodium ionophore monensin decreased T3 uptake by 51% at a concentration of 20 microM. These results indicated the existence of a sodium-related mechanism of T3 uptake into mouse thymocytes that does not operate for T4 uptake. PMID- 1915099 TI - Thyrocyte migration and histiotypic follicle regeneration are promoted by epidermal growth factor in primary culture of thyroid follicles in collagen gel. AB - The effect of epidermal growth factor (EGF) on the morphology of porcine thyroid follicles cultured in collagen gel was studied by light and electron microscopy. Treatment with EGF (10 ng/ml) for 1-4 days induced a progressive migration of thyrocytes radiating from the mother follicles into the collagen lattice. Migrating cells were often connected with junctional complexes, thus forming small follicles containing microlumina, in which the limiting portion of the plasma membrane expressed microvilli. Autoradiography of [3H]thymidine incorporation in EGF-treated cultures showed that more than 80% of nuclei in mother follicles and migrating cells were labeled after 4 days. TSH (2 mU/ml) given simultaneously with EGF did not influence the effect of EGF on multiplication, migration, and formation of microfollicles. TSH given for 12 h after 4 days of exposure to EGF was able to induce luminal dilation of mother follicles, but caused no change in the appearance of microlumina. It is concluded that thyrocytes in collagen gel retain epithelial characteristics during prolonged stimulation with EGF, in spite of a migrating response. The whole sequence of events, starting with the intact follicle, i.e. multiplication, migration of thyrocytes, and formation of new follicles, could, thus, be visualized to occur in response to a single mitogen, EGF. EGF might be involved in the generation of new follicles in the intact gland. PMID- 1915100 TI - Analysis of the thyroglobulin internalization process using in vitro reconstituted thyroid follicles: evidence for a coated vesicle-dependent endocytic pathway. AB - We have designed a new experimental system based on in vitro reconstituted thyroid follicles (RTF) to study the relative implication of macropinocytosis and micropinocytosis processes in the internalization of thyroglobulin (Tg). Thyrocytes cultured in the presence of TSH reorganize in histiotypic and functional follicles. Tg, which accumulates into the newly formed intrafollicular lumen (IL), was pulse labeled with [125I]iodide. Basal or TSH-activated Tg internalization, i.e. transfer from IL to cells, was assessed by measuring [125I]Tg in the cells and the IL; the IL fraction was collected after selective opening of lumina by a short treatment of RTF in a calcium-free medium. We used the ratio between cellular and IL labeled Tg contents as an endocytic index. TSH caused a very rapid increase in the cellular uptake of labeled Tg; the endocytic index increased by a factor of 4-8. The TSH effect was maximum after 15-20 min. TSH had no effect when the chase-incubation was performed at 4 C, but exhibited the same stimulatory action in terms of both time course and amplitude of action at 20 and 37 C. The macropinocytosis-related cellular structures, the pseudopods, were never observed in RTF maintained at 20 C; they were rare at 37 C and only found after 30 min of TSH treatment. At 20 as well as 37 C, the action of TSH on Tg endocytosis was concentration dependent in the range of 0.05-10 mU/ml. A fraction of Tg internalized by thyrocytes was found in coated vesicles. The labeled Tg content of purified coated vesicles varied with the temperature of the chase-incubation and was increased in TSH-treated RTF. Taken together, these data show that endocytosis of Tg by thyroid follicular cells in resting or moderately activated states does not proceed via the pseudopod formation-dependent mechanism, also termed macropinocytosis. Tg internalization would be related to what is referred as micropinocytosis and would involve a coated vesicle-dependent endocytic pathway. PMID- 1915101 TI - Thyroglobulin internalized by thyrocytes passes through early and late endosomes. AB - We have tried to characterize the intracellular compartments involved in the traffic of the thyroid prohormone thyroglobulin (Tg) from the site of storage, the follicular lumen, to the expected site(s) of proteolytic degradation, lysosomes. Electron microscope immunogold labeling with antibodies against Tg, cation-independent mannose-6-phosphate receptor (MPR), or arylsulfatase-A (ArS-A) was used to identify endocytic structures. The implication of these structures in the transport of Tg was analyzed by following the internalization and intracellular fate of Tg-colloidal gold complexes microinjected into the thyroid follicular lumen. Immunogold labeling was performed on ultrathin cryosections of intact pig tissue, in vitro reconstituted thyroid follicles (RTF), and isolated vesicles prepared by differential and isopycnic centrifugation. Microinjection experiments were carried out on RTF. Using double labeling for MPR and ArS-A, we characterized three types of structures: those slightly positive for MPR and ArS A, those strongly positive for both markers, and those only positive for ArS-A. These compartments exhibited the properties of early endosomes (EE), late endosomes (LE), and lysosomes (L), respectively. Tg immunoreactivity was high in EE, low in LE, and undetectable in L. Similar morphological and immunochemical characteristics of EE, LE, and L were found in intact tissue, RTF, and isolated vesicles. Tg-gold complexes microinjected into the lumen of RTF were efficiently internalized within 5 min into structures with the appearance of EE. Sixty minutes after the injection, Tg-gold complexes were detected into LE and L. We present here the first direct experimental evidence for an involvement of endosomal compartments in the Tg internalization/degradation pathway. The data indicate that internalized Tg molecules are transported to EE and then transferred from EE to LE. PMID- 1915102 TI - Nerve growth factor modulates the activation of the hypothalamo-pituitary adrenocortical axis during the stress response. AB - In the present study, we have investigated the functional relationship between the nerve growth factor protein (NGF) and the hypothalamus-pituitary adrenocortical axis (HPAA). We have found that while iv injected NGF is able to stimulate the HPAA activity in rats, NGF is not able to stimulate the axis after a block of the hypothalamus produced by chlorpromazine-morphine-Nembutal treatment. Also, the stress activation of the HPAA is significantly reduced by pretreatment of the rats with anti-NGF immunoglobulin G. These results suggest that the stimulatory action of NGF on HPAA activity requires the release of ACTH secretagogues from the hypothalamus and that NGF may modulate the HPAA response to stress stimuli. PMID- 1915103 TI - Enhanced insulin secretory response to acetylcholine by perifused pancreas of 5 day-old preobese Zucker rats. AB - The insulin secretion rate in response to different secretagogues and neurotransmittors was studied in perifused pancreas of 5-day-old lean (Fa/Fa) and preobese (fa/fa) Zucker rats. Glucose (16.6 mM) alone or in combination with 20 mM arginine or 5 mM theophylline induced a net stimulation of insulin secretion. This effect was similar in the two groups. By contrast, the stimulatory effect of acetylcholine on glucose-induced insulin secretion was significantly higher in preobese pups than in lean rats. There was also a tendency toward a higher inhibitory effect of norepinephrine on insulin secretion in preobese than in lean rats, but this difference did not reach statistical significance. Together these results demonstrate a normal insulin secretion in response to nutrient secretagogues in preobese fa/fa rats but an enhanced effect of acetylcholine. This latter effect may be related to the changes in the autonomic nervous system activity, which is usually described in obese fa/fa rats. PMID- 1915104 TI - Skeletal effects of calcitonin in ovariectomized rats. AB - Although calcitonin (CT) has been shown to be effective for the prevention of bone loss in early postmenopausal women, the skeletal effects of the hormone specifically during the early stages of estrogen deficiency have not been characterized histomorphometrically to date. The current study involves use of the ovariectomized (OVX) rat as an animal model for early postmenopausal bone loss to perform such a histomorphometric analysis. One group of OVX rats was injected sc with salmon CT on alternate days for a 6-week period. Additional groups of OVX and sham-operated control rats were treated with vehicle alone. In comparison to control rats, the proximal tibia of vehicle-treated OVX rats were characterized by a 3-fold decrease in cancellous bone volume and significant increases in osteoblast surface (+200%), osteoclast surface (+143%), mineralizing surface (+111%), mineral apposition rate (+36%), bone formation rate (+181%), and longitudinal bone growth (+38%). In contrast, treatment of OVX rats with CT normalized tibial cancellous bone volume and significantly decreased all of the above cellular- and fluorochrome-based indices of bone turnover to near control levels. The results indicate that CT treatment depresses bone turnover and prevents the development of osteopenia in OVX rats. These findings are consistent with the bone protective effect of CT in early postmenopausal women and further support the OVX rat as an animal model for the preclinical evaluation of prophylactic treatments for postmenopausal bone loss. PMID- 1915105 TI - Alteration of proto-oncogene c-fos expression in neonatal estrogenized BALB/c female mice & murine cervicovaginal tumor LJ6195. AB - Experiments were performed to determine the effect of neonatal estrogen treatment on the expression of the proto-oncogene c-fos in the BALB/c mouse cervicovaginal tract. Estradiol induces the expression of c-fos in the normal mouse cervicovaginal tract. However, c-fos expression was not stimulated by estradiol in the cervicovaginal tracts of mice that received neonatal estrogen treatment. In addition, the level of expression of c-fos by the estrogen- and progesterone induced murine cervicovaginal LJ6195 tumor was similar to that in the normal vaginal tract following estradiol stimulation and was not regulated by estradiol. PMID- 1915106 TI - Pituitary adenylate cyclase-activating polypeptide (PACAP) potentiates the gonadotropin-releasing activity of luteinizing hormone-releasing hormone. AB - In order to determine if the newly discovered neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP), interacts with the known hypothalamic releasing factors to modulate pituitary hormone secretion, the effect of PACAP, either alone or in combination with either LHRH, TRH, CRF or GHRH, was examined in rat anterior pituitary cell cultures. While PACAP alone weakly stimulated LH and FSH release, PACAP and LHRH, in combination, interacted synergistically to stimulate gonadotropin secretion. No significant changes in the secretion of either TSH, ACTH, or GH were observed in response to PACAP, either alone or in combination with the other releasing factors. Addition of an LHRH antagonist demonstrated that the PACAP effect on gonadotropin release was neither mediated by the LHRH receptor nor the result of LHRH contamination of the PACAP preparation. Because of the sequence homology (68%) between the N-terminal 28 amino acids of PACAP and VIP, the addition of a VIP antagonist was used to demonstrate that the PACAP effect is not mediated through the VIP receptor. The observation that PACAP interacts synergistically with LHRH in stimulating gonadotropin release suggests intriguing possibilities for PACAP in regulating gonadotropin secretion and reproductive function. PMID- 1915107 TI - Renin-dependency of glycyrrhizin-induced pseudoaldosteronism. AB - A prospective study was carried out on 12 patients with chronic hepatitis who were taking 546 mg/day of glycyrrhizin for 4 weeks in order to identify the factors responsible for the development of hypertension and hypokalemia. In 5 patients, blood pressure increased and serum potassium decreased after the treatment (responders). In the remaining 7 patients, these values were unchanged (nonresponders). There were no significant differences in age, plasma aldosterone, the catecholamine concentrations or serum transaminases. The basal plasma renin activity (PRA) in the responders was more than 1.5 ng/m/h (2.5 +/- 0.3 ng/m/h), while that in the non-responders was less than 1.5 ng/m/h (0.7 +/- 0.1 ng/ml/h). Furthermore, a positive correlation between the basal RPA and the changes in blood pressure, and a negative correlation between the basal PRA and the changes in potassium were found. These results suggest that patients with higher PRA levels are more likely to develop hypertension and hypokalemia when treated with glycrrhizin. PMID- 1915108 TI - Localization of kallikrein in rat pineal glands. AB - The presence of kallikrein mRNA has been reported in the pineal gland of rats. Using an antibody to rat tissue kallikrein, we immunohistochemically examined the localization of cell components producing tissue kallikrein in this gland. The kallikrein immunoreactive cells were scattered in the parenchyma of the pineal gland. Their cell bodies were polymorphic with cell processes and a large nucleus similar to that of the pinealocyte. Frequently immunoreactive materials were seen to be localized in the perivascular areas. PMID- 1915109 TI - Application of improved coupling assay method for peroxidase of diseased thyroids: report of three cases. AB - Recently we have developed an assay method for peroxidase-catalyzed coupling of iodotyronine residues of thyroglobulin, which is applicable to human diseased thyroid tissues. In the present study, the assay method as well as usual peroxidase assay methods were applied to thyroids of three patients (No. 1: familial goiter with impaired thyroglobulin synthesis, No. 2: mild chronic thyroiditis, No. 3: dyshormonogenetic goiter) who showed organification of iodine with high TSH levels and low thyroid hormone levels in sera. In general, these patients showed relatively high activities measured by guaiacol oxidation assay, iodide oxidation and coupling assay compared with those of control thyroids. Iodothyronine content in thyroglobulin was very low except thyroxine in No. 2. These results indicate that factors other than peroxidase may be responsible for the cause of the hypothyroid state. The coupling assay method used here is therefore useful for the detection of the 'coupling defect' in patients in a hypothyroid state. PMID- 1915110 TI - Intranasal administration of His-D-Trp-Ala-Trp-D-Phe-LysNH2 (growth hormone releasing peptide) increased plasma growth hormone and insulin-like growth factor I levels in normal men. AB - The effects of intranasal and iv administration of His-D-Trp-Ala-Trp-D-Phe-LysNH2 (GHRP) on plasma GH, PRL, LH, FSH, TSH, cortisol, insulin, IGF-I as well as GHRH like immunoreactivity (LI) levels were examined in 6 healthy male subjects. An iv bolus injection of GHRP(1 micrograms/kg BW) caused a remarkable increase in plasma GH levels with a mean (+/- SE) peak of 54.9 +/- 4.2-micrograms/L. In addition an intranasal administration of GHRP resulted in a significant, dose related increase in plasma GH with peaks of 39.6 +/- 15.3 micrograms/L at a dose of 30 micrograms/kg BW, 14.1 +/- 5.0 micrograms/L at 15 micrograms/kg BW and 7.5 +/- 5.7 micrograms/L at 5 microgram/kg BW. Plasma PRL and cortisol levels were slightly but significantly increased after iv administration of GHRP, whereas GHRP totally failed to affect plasma TSH, LH, FSH, insulin, blood sugar and GHRH LI levels. Seven consecutive, intranasal administrations of 15 micrograms/kg BW GHRP every 8h were well tolerated in all subjects examined. During this treatment, GH responsiveness to GHRP was not attenuated by desensitization and plasma IGF-I was increased from 94.5 +/- 5.8 micrograms/L before GHRP to 125.8 +/ 6.0 micrograms/L after repeated GHRP administration. These findings indicate that intranasal administration of GHRP stimulates GH secretion and consequently enhances IGF-I production in normal subjects. If GHRP is demonstrated to be beneficial in the treatment of some patients with GH deficiency, the intranasal route of administration may be more useful than the painful injection because a prolonged period is required for the treatment. PMID- 1915111 TI - Growth hormone (GH) profiles with successive provocation by GH-releasing hormone and arginine in children: a clinical appraisal. AB - To establish a single and reliable test for evaluating growth hormone (GH) secretion, we examined successive GH provocation by two agents with different modes of action, GH releasing-hormone (GHRH) and arginine (Arg) in 60 children of short stature, 6 patients with pituitary dwarfism and 9 normal young adults. Their GH profiles were qualitatively classified into 4 types: 25 children and 7 adults responded to both stimuli with 2 GH peaks (48.7 +/- 4.3 [SEM] micrograms/L for GHRH and 32.2 +/- 2.6 micrograms/L for Arg in children; 25.8 +/- 7.6 micrograms/L and 30.1 +/- 9.2 micrograms/L respectively in adults) (type A). A single peak for GHRH (57.7 +/- 4.6 micrograms/L) without an Arg-induced peak was obtained in 29 younger children (type B), which is considered to be a GHRH dominant pattern. Two of them were diagnosed as hypothalamic GHRH deficiency based on a low nocturnal plasma GH and good response to GH treatment. Six adolescents and 2 adults showed a blunted response to GHRH (9.0 +/- 1.1 micrograms/L) but a normal response to Arg (40.6 +/- 9.5 micrograms/L) (type C), which appears to be caused by somatostatin (SRIH) hypertonicity. None with pituitary dwarfism responded to both stimuli (4.5 +/- 1.3 and 2.3 +/- 0.5 micrograms/L). Thus, the GHRH-Arg test makes it possible to evaluate the counterbalance between GHRH and SRIH as well as to differentiate pituitary GH deficiency from hypothalamic GHRH dysfunction. PMID- 1915112 TI - Effects of TAP-144-SR, a sustained-release formulation of a potent GnRH agonist, on experimental endometriosis in the rat. AB - A new, simple experimental endometriosis model was established by auto transplanting endometrial tissue fragments beneath kidney capsules in female rats. The transplanted endometrial tissue grew well, forming a fluid-filled cyst, which reached maximal size 2 to 3 weeks after transplantation. The growth and maintenance of the transplants was dependent on the ovary: ovariectomy induced regression of well grown transplants. The therapeutic effects of TAP-144-SR (biodegradable microcapsules of copoly (DL-lactic/glycolic acid) copolymer containing a potent GnRH agonist, TAP-144 (D-Leu6-[des-Gly10-NH2]-GnRH ethylamide, leuprolide acetate) were studied with this rat endometriosis model. A single sc injection of TAP-144-SR (corresponding to 1, 10 or 100 micrograms/kg/day of TAP-144), suppressed the growth of the transplanted endometrial tissues and uterine weight in a dose-dependent manner. At 100 micrograms/kg/day, the suppressive effect was more marked in rats given TAP-144 SR than in those given TAP-144 solution. The extent of suppression was comparable to that caused by ovariectomy. Serum and pituitary concentrations of LH and FSH were also reduced more markedly by the administration of TAP-144-SR than by TAP 144 solution. From these results, the present endometriosis model was found to be useful for the evaluation of compounds with potential therapeutic activity. The sustained-release formulation of TAP-144 seems to be beneficial over its solution in terms of both convenience and efficiency for therapy of patients with endometriosis. PMID- 1915113 TI - Effect of media conditioned by concanavalin A activated spleen cells on pancreatic islet cells. AB - The effect of media conditioned by concanavalin A-activated spleen cells (C-sup) on insulin release and its islet cell cytotoxicity were studied. In a functional study, C-sup significantly inhibited both basal insulin release and glucose stimulated insulin release. Morphologically, C-sup had a destructive effect on isolated islets after 72 h incubation. Islet cell cytotoxicity was shown by lactate dehydrogenase (LDH) release assay after 5 days incubation with C-sup in a dose-dependent manner. These results suggest that acceleration of the onset of diabetes in young diabetes prone (DP) Bio-Breeding/Worcester (BB/W) rats following the injection of C-sup may depend on the suppressive and cytotoxic effects of C-sup on pancreatic islet cells. PMID- 1915114 TI - Effects of estrogen on growth of androgen-responsive rat prostatic tumor (R 3327). AB - It has been known that estrogen has synergistic effects with androgen on growth of normal male accessory sex organs of rats. The present study was therefore undertaken to examine the effects of estrogen on androgen-responsive rat Dunning R 3327 prostatic tumor. The weight of male accessory sex organs was suppressed by estrogen on growth of treatment, but synergistic effects of estrogen and androgen on these organs were seen following combined treatment with androgen and estrogen. In contrast to the effects of estrogen on accessory sex organs, estrogen influenced a R 3327 tumor only in the negative direction regardless of whether androgen was injected simultaneously or not. When the dihydrotestosterone injection was reduced from 500 to 100 micrograms/rat/day after the tumor appeared as subcutaneous nodules, the weight of the accessory sex organs was similar to that of the control animals. However, this amount of dihydrotestosterone increased tumor growth equally when compared to those treated with a pharmacological dose of dihydrotestosterone. Therefore, the response of R 3327 tumor to androgen was different from that of the accessory sex organs. PMID- 1915115 TI - Reduced brown adipose tissue thermogenesis and metabolic rate in pre-obese mice treated with monosodium-L-glutamate. AB - To clarify whether reduced brown adipose tissue (BAT) thermogenesis and resting metabolic rate (RMR) are the cause or the consequence of obesity in monosodium-L glutamate (MSG)-treated mice, we measured guanosine-5'-diphosphate (GDP) binding, and oxygen consumption in the interscapular BAT (IBAT) mitochondria, and the RMR in pre-obese (3-week-old) and obese (12-week-old) MSG-treated mice. Decreases in IBAT mitochondrial GDP binding and oxygen consumption as well as lowered RMR in MSG-treated mice were found even in the pre-obese stage as well as the obese stage, when compared to those in control mice. These findings suggest that reduced BAT thermogenesis may be one of the contributing factors in the development of obesity. PMID- 1915116 TI - In vivo effect of thyrotropin on intracellular translocation of thyroid peroxidase in rat thyroid cells by an indirect immunofluorescence method. AB - The in vivo effect of thyrotropin (TSH) on the intracellular localization of thyroid peroxidase (TPO) in rat thyroid epithelial cells was examined by an indirect immunofluorescence method. The staining for TPO in the epithelial cells of normal rats appeared all over the cytoplasm, especially in the apical region. The injection of propylthiouracil for 3-10 days increased the staining in the apical region. The administration of L-thyroxine for 7-10 days to normal rats abolished the relatively high localization of TPO in the apical region, and resulted in TPO staining all over the cytoplasm. Six hours after TSH was injected into the thyroxine-treated rats, localization of TPO staining in the apical region was observed. These results suggest that TSH may play a role in the translocation of preexisting TPO to the apical region before TSH-induced biosynthesis becomes evident. PMID- 1915117 TI - Heterogeneity of non-insulin-dependent diabetes mellitus in HLA types and clinical features: comparison with insulin-dependent diabetes mellitus. AB - We determined HLA types in 110 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and studied the relationship between the HLA phenotypes and clinical features. Sixty-nine patients with insulin-dependent diabetes mellitus (IDDM) and 100 healthy blood donors served as controls. Concerning HLA DR and DQ loci, frequencies of DR4, DRw9 and DQw3.2 were higher, and those of DR2, DRw8, DRw11, DRw12 and DQw1 were lower in patients with IDDM compared than in healthy controls. There were no differences between NIDDM and normal controls in the frequency of a particular HLA DR antigen except for a decreased frequency in DRw11 in the former. The frequency of DQw3.2 antigen in NIDDM was intermediate between IDDM and normal controls. There were some differences between DQw3.2 positive and -negative NIDDM patients in clinical features. Those who showed low C-peptide responses during oral glucose tolerance test were more frequently found among DQw3.2-positive NIDDM patients. These results suggest that Type 1 diabetes mellitus may have a mild clinical course and is found among the Japanese NIDDM population. PMID- 1915118 TI - Detection of thyroid microsomal and thyroglobulin antibodies by new sensitive radioimmunoassay in Hashimoto's disease; comparison with conventional hemagglutination assay. AB - We evaluated clinical usefulness of thyroid microsomal antibody (MCAb) and thyroglobulin antibody (TGAb) measured by new sensitive radioimmunoassays (RIA). These assays are simple and reproducible; the intra- and inter-assay coefficients of variation were 3.6-6.8% and 6.6-13.2% in the MCAb assay, and 3.2-7.7% and 7.6 12.3% in the TGAb assay, respectively. In 126 patients with Hashimoto's disease, the antibody activity determined by this RIA correlated with that determined by the hemagglutination assay (HA) (r = 0.848 for MCAb, r = 0.686 for TGAb, p less than 0.001). MCAb was detected by RIA in all of 115 HA-positive and 4 of 11 HA negative patients, and TGAb by RIA in all of 84 HA-positive and 29 of 42 HA negative patients: the prevalence of MCAb was 94% and that of TGAb was 90% in the disease. Moreover, some showed high antibody activity only in RIA. In another group of 14 patients with biopsy-proved Hashimoto's disease with no antibody activity by routine HA tests, serum MCAb was detected in 3 (21%), TGAb in 11 (79%), and both activities in 2 (14%). Our results indicate that (1) the RIA tests are more sensitive than the conventional HA test, and that (2) the present RIA test for TGAb is more sensitive than that for MCAb in detecting autoimmune abnormalities, especially in patients with biopsy-proved Hashimoto's disease who give negative results in the HA test. PMID- 1915119 TI - Prevalence of apical periodontitis and results of endodontic treatment in middle aged adults in Norway. AB - The present investigation based on a random sample of 50-year-olds from Oslo, Norway, indicate a prevalence of apical periodontitis of 3.5% of the teeth present. Forty-four percent of the endodontically treated teeth presented with a radiographically detectable periapical radiolucency. There was a statistically significant negative correlation between the quality of the root fillings evaluated and prevalence of apical periodontitis. PMID- 1915120 TI - Dynamic resistance of teeth: technical considerations and applications of an experimental device. AB - Tooth fracture by impact is the most common cause of fracture in human incisors. We have designed an experimental system to measure the dynamic fracture force of teeth in vitro, and initial results obtained from a sample of healthy, recently removed human incisors are reported. The method was reproducible and reliable, and the results provide a baseline for studies evaluating the effect of endodontic procedures on the dynamic fracture force of teeth. PMID- 1915121 TI - SEM study of surface architecture of gutta-percha cones. AB - The apical third of 60 standardized, gutta-percha cones obtained from six different manufacturers were analyzed by scanning electron microscopy. Despite the fact that the majority of the commercial gutta-percha cones showed rather uniform and smooth surfaces, some displayed morphologic variations such as gross protuberances or deeply cratered areas containing numerous free or entrapped crystal-like particles. PMID- 1915123 TI - Tissue reactions after experimental luxation injuries in immature rat teeth. AB - Immature permanent teeth often develop complications after luxation injuries. The pathology and the degenerative processes of the complications, however, are not well understood. In this study, we histologically examined the long-term reactions of immature rat teeth after standardized luxation injuries delivered in our previously developed experimental model. The upper first molars of 3-week-old male Wistar rats weighing 50-60 g were pushed horizontally toward the palate to cause a constant amount of dislocation. The follow-up changes of the luxated molars were studied up to 56 days after the trauma. Soon after the trauma, the periodontium had irregular fibers, degenerated cells, hemorrhage and edema in various places. After 12 h, a cell free area appeared in the palatal periodontium. In the alveolar bone and on the surface of the root, resorption occurred one day and 5-7 days after injury respectively. Although the damage in the periodontium and alveolar bone was gradually repaired, the root resorption, especially in the palatal cervical region, continued throughout the experimental period. In the most cases, the dental pulp did not seem to be damaged immediately after the trauma. By the 3rd day after injury, however, displacement of odontoblasts into the dentinal tubules was observed in many teeth. Moreover, formation of irregular dentin was observed in some teeth after 7 days. These changes of the pulp tended to disappear in the later stages of the experiment. PMID- 1915122 TI - In vivo efficacy of various retrofills and of CO2 laser in apical surgery. AB - The purpose of the present study was to radiographically assess the efficacy of various retrofilling materials and of the use of CO2 laser in apical surgery. The mandibular premolars of six beagle dogs were infected, resulting in periapical lesions. Apical surgery was performed without root canal treatment. Amalgam with cavity varnish, glass ionomer cement and a lightcured composite resin were the retrofilling materials used. In half of the material CO2 laser was used on the root surface and the bone, for occlusion of the dentinal tubuli and sterilization. The healing following surgery was observed radiographically for six months. The highest success rate (89%) was found in the roots retrofilled with amalgam and varnish, and the lowest (60%) in those retrofilled with the composite resin. The difference between these groups was statistically significant. The success rate following retrofilling with glass ionomer cement was 69%, and was not significantly different from both the other groups. Under the conditions of this study, the use of CO2 laser during surgery did not affect the treatment results. PMID- 1915125 TI - Effects of the penetration of a root canal filling material into the mandibular canal. 2. Changes in the alveolar nerve tissue. AB - The root canal filling material "Vitapex" (Neo Dental Chemical Products Co., Tokyo), made of calcium hydroxide and iodoform with the addition of silicone oil, was experimentally injected into the mandibular canals of dogs, and its effect on the alveolar nerve tissue was examined by light and electron microscopy. No change was observed as long as the injected paste did not come into direct contact with the nerve, but tissue damage was found at sites of direct contact. After removal of degenerated nerve debris by macrophages and Schwann cells, the persisting external membranes or "Schwann tubes" appeared to provide a scaffolding for axonal regeneration and Schwann cell proliferation. PMID- 1915124 TI - Effects of the penetration of a root canal filling material into the mandibular canal. 1. Tissue reaction to the material. AB - The root canal filling paste Vitapex (Neo Dental Chemical Products Co., Tokyo), made of calcium hydroxide and iodoform with the addition of silicone oil, was experimentally introduced into the mandibular canals of 29 dogs. Tissue reactions to the paste were examined by radiography, histopathology, and electron microscopy. These examinations revealed that the paste was phagocytosed by macrophages and, in general, was gradually resorbed over time. The paste was also found to cause heterotopic calcification and/or ossification within the area of original penetration. PMID- 1915126 TI - Epinephrine permeation across dentin in vitro. AB - The permeation of epinephrine across human dentin discs was studied in vitro. Permeation was measured across dentin of two different thicknesses, with and without the presence of smear layers. Epinephrine was readily detected at the earliest measured time (10 min) and reached peak concentrations between 30 and 50 min. Epinephrine flux (concentration multiplied by the volume of the effluent per min) increased with decreasing thickness of the discs and increased significantly with the removal of the smear layer. The T 1/2 (half-time in min necessary to reach steady-state diffusion of epinephrine) decreased as dentin thickness was reduced and fell further in the absence of the smear layer. This study suggests that the permeation of epinephrine across dentin is inversely related to dentin thickness and retarded by the presence of a smear layer. Also, the topical use of 1 mg/ml epinephrine produced therapeutically useful drug concentrations, but the rate of permeation was relatively slow. PMID- 1915128 TI - Thermomechanical compaction of gutta-percha: a scanning electron microscope study. AB - The root canals of 20 freshly extracted maxillary central incisors and canines were prepared and filled by thermo-mechanical or lateral condensation of gutta percha cones without sealer. The adaptation of the filling material to the root canal walls was then examined with a scanning electron microscope. A more homogenized mass of gutta-percha could be detected in teeth filled by thermomechanical compaction of gutta-percha cones. The morphology of the prepared root canal system was well reproduced by the use of both techniques. PMID- 1915127 TI - Dentine hypersensitivity: a review. AB - Dentine hypersensitivity is a relatively common pain condition. Local pulpal inflammation, traumatic oral hygiene and dietary habits have been considered in the etiology of dentine hypersensitivity. Dentine hypersensitivity is probably caused by a change in fluid flow in the dentinal tubules, which in turn excites the nerve endings located at the pulp-dentine border. Consequently, treatment success would depend on the prevention of fluid flow across the dentinal tubules (sodium fluoride, stannous fluoride, sodium monofluorophosphate, strontium chloride, sodium citrate, potassium oxalate, and resins/adhesives), or on the desensitization of the nerve endings located at the pulp-dentine border (potassium nitrate). Although a wide variety of treatment methods have been available, clinical data is characterized with ambiguity, warranting further research of the factors which could possibly be implicated in the occurrence of dentine hypersensitivity. PMID- 1915129 TI - Histometric study of the effect of occlusal alteration on periodontal tissue healing after surgical injury. AB - The effect of occlusal alteration upon healing of the periodontium after surgical injury was studied in 62 male Wistar rats, nine weeks of age. An osteotomy was made with a bur through the vestibular bone plate, the periodontal ligaments and into the superficial part of the root surface of the first mandibular molar. In the same session, the occlusion of the antagonistic tooth was altered in the experimental groups by either placing a high amalgam restoration, grinding, or extraction. The occlusion in the control group was unaltered. The rats were killed 70 days after surgery, and examined histologically. A histometric registration of the periodontal repair revealed a significant narrowing of the periodontal ligament width in the non-occluding teeth, as well as significant thickening of cementum at and above the surgical cavity site. The hypo- and hyper occluding teeth did not show significant changes as compared to the controls. PMID- 1915130 TI - Healing of the guinea pig incisor after partial pulp removal. AB - A histological and microradiographical study was made of eruption and healing of guinea pig lower incisors after endodontic treatment compared with intact incisors. One incisor per animal was cut perpendicularly at the level of the gingiva. One third to one half of the pulp was removed. The experimental periods were 0, 4, 7, 16, 21 and 31 days. Unstained, HE or Brown and Brenn stained sections were studied microscopically. Some teeth were sectioned undecalcified and studied microradiographically. In intact incisors the dentin matrix deposition and mineralization were described. In the dentin, incisally to the pulp proper, narrow canals, the walls of which consisted of mineralized material, were found opening at the occlusal surface. Histologically, in the treated teeth, a beginning of cell-rich fibrodentin deposition at the original dentin wall was present at Day 4. At Day 7 a substantial walling off of the pulp is achieved by cell-rich and some cell-poor fibrodentin. After 16 days large amounts of cell rich and cell-poor fibrodentin were covered by some tertiary dentin. After 31 days the amount of tertiary dentin was larger than after 16 days and also covered the incisal part of the root canal walls. Further apically some vasodentin and newly formed normal, secondary, dentin was observed. In course of this period the cells of the cell-rich and cell-poor fibrodentin first showed necrobiosis, then necrosis. The cell-rich fibrodentin appeared not fully mineralized. All blood vessels and strands of soft tissue which ran in canals in the fibrodentin came to a dead end. Thus the root canal was fully obturated. Although the teeth appeared (nearly) normal to the naked eye and radiographically after 31 days, histologically they were not. Large amounts of fibrodentin still being present incisally which showed the dual potential of the guinea pig pulp to produce both fibrodentin and orthodentin. PMID- 1915131 TI - In vitro efficacy of sodium perborate preparations used for intracoronal bleaching of discolored non-vital teeth. AB - Bleaching materials containing 30% hydrogen peroxide have been used successfully for the treatment of discolored non-vital teeth. Intracoronal application of these materials was occasionally associated with the development of external root resorption. Extracted human teeth with intact crowns were discolored in vitro and bleached with three preparations of sodium perborate. These preparations included: sodium perborate with 30% hydrogen peroxide, sodium perborate with 3% hydrogen peroxide and sodium perborate with water. The bleaching materials were placed in the pulp chamber of the discolored teeth and sealed with IRM for 14 days. They were replaced with fresh preparations after 3 and 7 days. The coronal tooth shades were evaluated after 3, 7 and 14 days and a comparison of the bleaching success of the groups was made at each interval. It was found that after 14 days and three bleachings there was no significant difference in success between the groups. It is therefore recommended that sodium perborate be used in combination with water rather than with hydrogen peroxide to reduce the risk of post-bleaching external root resorption. PMID- 1915132 TI - Cytotoxicity of eugenol in sealer containing zinc-oxide. AB - In this study two zinc-oxide-based root canal sealers were compared for their tissue toxic response. The sealers tested were zinc-oxide eugenol and zinc-oxide glycerine. Fifteen albino rats were used for the study and were injected subcutaneously in the preset state. The tissue response was assessed by counting the polymorphonuclear cells at Day 1, Day 7 and Day 15 of the study period. The inflammatory response was graded according to the mean polymorphonuclear counts in the five rats for each period. The results showed that the toxicity was greater for the eugenol-containing sealer and increased during the three time intervals. For the non-eugenol sealer the response was milder and reached a peak by 7 days after which it decreased. PMID- 1915133 TI - Endoscopic treatment of anastomotic strictures in Crohn's disease. AB - The results of endoscopic balloon dilatation in 27 patients with anastomotic strictures caused by Crohn's disease are reported. All patients had obstructive symptoms not responding to corticosteroids and of such a degree that resection or strictureplasty was considered necessary. The patients were followed up for 7 to 38 months after their first dilatation. Eighteen patients were more or less free from obstructive symptoms while the results were less favourable in the remaining nine patients. The median time after the latest surgical intervention was seven years in the group with a successful outcome and 1.6 years in the group with a poor outcome, which may indicate that some patients have a more aggressive form of Crohn's disease where balloon dilatation is only of moderate value. However, all patients experienced at least a temporary effect, so that balloon dilatation can be considered for use in situations where it is desirable to postpone surgery. PMID- 1915134 TI - Anticholinergic medication in diagnostic endoscopy of the upper gastrointestinal tract. AB - The effects of two different forms of anticholinergic medication on endoscopic quality and patient discomfort were studied in 235 consecutively observed out patients. Patients were randomized to receive either scopolamine i.v. and placebo transdermally, saline i.v. and saline transdermally, or placebo i.v. and scopolamine transdermally. No differences could be observed between the groups with respect to gastric motor function or endoscopic quality (as judged by the endoscopist), or discomfort during endoscopy (as judged by the patient). Transdermally applied scopolamin resulted in a significant increase (2p = 0.002) in post-endoscopy discomfort due to dryness of the mouth. The findings speak against the use of i.v. scopolamine (20 mg) or transdermally applied scopolamine (0.5 mg) in endoscopy of the upper gastrointestinal tract. PMID- 1915135 TI - Diazemuls versus diazepam as premedication in upper gastrointestinal endoscopy: a randomised cross-over study. AB - The efficacy and tolerability of Diazemuls versus conventional diazepam as endoscopic premedication was evaluated in a study with a cross-over design performed in 26 patients undergoing upper gastrointestinal tract endoscopy. No statistically significant differences were found between the two forms of premedication with regard to degree of sedation, patient compliance or recovery of psychomotor function. With respect to short-term amnesic effects, efficacy and tolerability Diazemuls was comparable to the conventional formulation of diazepam. Diazemuls may therefore be proposed as an alternative premedication for endoscopy. PMID- 1915136 TI - The duodenum in liver cirrhosis: endoscopic, morphological and clinical findings. AB - Endoscopic studies were performed to determine whether changes occurred in the duodenum related to portal hypertension in patients with liver cirrhosis. The total of 271 patients studied were subdivided into three groups: 83 patients with liver cirrhosis and portal hypertension, 53 with liver cirrhosis but no portal hypertension, and 135 controls. In the duodenum of cirrhotic patients with portal hypertension several changes were observed on endoscopy that were also present in the other two groups. Atrophy and vascular malformations, however, were present only in the duodenum of cirrhotic patients with portal hypertension, although in only a few patients and with statistical significance only for vascular malformations (p less than 0.01, phi = 0.21). Eleven percent of the patients had more than one endoscopic finding, but the associations of findings were without statistical significance. No statistically significant correlation was observed between the clinical severity of cirrhosis or the severity of esophageal varices and the endoscopic findings. Finally, there was no statistically significant difference between the histological findings of duodenitis in the three groups of patients. PMID- 1915137 TI - Use of an alternative guidewire system in endoscopic placement of biliary endoprosthesis. AB - A new guidewire with increased flexibility, torque control and a new smooth outer coating has been designed for use in interventional vascular radiology. The successful use of an adaptation of it in endoscopic management of malignant biliary strictures is reported. PMID- 1915138 TI - Information requirements and sedation preferences of patients undergoing endoscopy of the upper gastrointestinal tract. AB - Patients' attitudes to sedation and their information needs before undergoing endoscopy were investigated using a questionnaire. One hundred and two patients completed the study; 32 had undergone endoscopy before. Sixty-six (94%) of the new patients and all follow-up patients knew why they were undergoing the procedure; 65 (93%) new and 28 (88%) follow-up patients understood how the procedure was carried out. Forty-one percent of the new and 25% of the follow-up patients wanted an information booklet about their disease and its management. Most patients chose to be sedated during the endoscopy. The proportion wishing to be sedated did not differ significantly between the new and follow-up patient groups. Sedation and information should be offered to all patients undergoing endoscopy. PMID- 1915139 TI - Cholangiosepsis: endoscopic drainage and antibiotic therapy. PMID- 1915140 TI - Clinical features, pathophysiology and relevance of portal hypertensive gastropathy. AB - The frequency and importance of gastric mucosal lesions in patients with portal hypertension have been increasingly recognized in recent years. This article describes the clinical and endoscopic features of portal hypertensive gastropathy and reviews the current state of knowledge concerning the pathophysiology and treatment of the disorder. PMID- 1915141 TI - Tube cecostomy as a cause of cecal pseudotumor. AB - A 60-year-old male presented with findings on radiographic and physical examination which were compatible with colonic obstruction. A tube cecostomy was performed. Colonoscopy seven months later revealed a pseudotumor composed of granulation tissue in the cecum at the site of the previous cecostomy. PMID- 1915142 TI - Endoscopic and histopathologic features of Degos' disease. AB - The case is reported of a 69-year-old female with atrophic papules on the skin who developed multiple spontaneous intestinal perforations of which she eventually died. The skin lesions in combination with lesions in the gastrointestinal tract are typical for Degos' disease or malignant atrophic papulosis. The characteristic histopathological and endoscopic features of this rare disease are reported. This case demonstrates the importance of routinely performing endoscopy in Degos' disease to detect silent perforation, even in patients without gastrointestinal complaints. PMID- 1915143 TI - Use of endoscopy to diagnose symptomatic duodenal duplication cyst in an adult. AB - The case of a female patient with a symptomatic duodenal duplication cyst diagnosed on endoscopy is reported. It is very important to discriminate between this rare anomaly and choledochocele as the treatment differs. Ultrasonography and ERCP are useful for the differential diagnosis. This rare anomaly is more often diagnosed in children. In adults duodenal duplication cysts may cause obstructive jaundice. The endoscopic finding of a cystic lesion in the medial wall of the second duodenal section at the papilla Vateri should be interpreted as a sign of the disease. PMID- 1915145 TI - Teaching by endoscopy simulation. PMID- 1915144 TI - Unusual presentation of a case of brain abscess after endoscopic injection sclerotherapy of esophageal varices. AB - Although an increasing number and variety of complications of endoscopic injection sclerotherapy (EIS) of bleeding esophageal varices have been reported, infectious complications are rare. A case of brain abscess following EIS is reported which was characterised by an unusual clinical presentation in that there was no fever or leucocytosis. This presentation could have led to the abscesses being mistaken for brain metastases. The outcome of antimicrobial therapy was favorable which provided further evidence in support of the diagnosis. PMID- 1915147 TI - Tension pneumoperitoneum after colonoscopic polypectomy. PMID- 1915146 TI - Is premedication necessary in diagnostic endoscopy of the upper gastrointestinal tract? PMID- 1915148 TI - Pneumoperitoneum following colonoscopy in a patient with a solitary rectal ulcer. PMID- 1915149 TI - Surgical treatment of retrograde jejunogastric intussusception after temporary endoscopic management. PMID- 1915150 TI - An endoscopic technique for stent recovery used after duodenal perforation by a biliary stent. PMID- 1915151 TI - Massive hemorrhage due to angiosarcomatosis diagnosed by intraoperative small bowel endoscopy. PMID- 1915152 TI - Modelling protein three-dimensional structure using tritium planigraphy. AB - We propose the use of data on the topography of the label-accessible surface of a protein molecule obtained by the method of tritium planigraphy as a criterion for choosing the optimal intermediate arrangements of alpha-helices in globular proteins so as to model their three-dimensional structures. This approach has been used for modelling the three-dimensional structure of parvalbumin III from pike. The proposed model has been compared with high-resolution X-ray structural data for a related protein, paryvalbumin from carp. The possibilities and limitations of this approach are discussed. PMID- 1915153 TI - Fourier transform infrared spectroscopy of aqueous dispersions of phosphatidylserine-cholesterol mixtures. AB - The effect of cholesterol on vibrational spectra in the non polar and in the polar region of dimyristoyl phosphatidylserine (DMPS) and of phosphatidylserine from bovine spinal cord (PS) has been investigated. The small shifts in the methylene CH stretching frequencies after taking into account the contribution of the cholesterol spectrum were interpreted as a combined effect of cholesterol on the conformation of the chains and of the lesser contributions of the cholesterol methyl groups. Cholesterol also influences the ratio of the trans (1465 cm-1) to the lower wavelength (1457 cm-1) CH2 bending bands. No significant direct effect of cholesterol on the vibration of the polar residues was discerned. The small shift of the carboxylate band observed below the phase transition is probably due to the change in the intermolecular zwitterions when the average distance between the neighboring polar groups increases due to incorporation of cholesterol molecules. PMID- 1915154 TI - Thermal transitions in the structure of tubulin. Environments of aromatic aminoacids. AB - The environment of aromatic aminoacids in the thermal transition of brain tubulin has been studied by several spectroscopic techniques (Fourth Derivative, Difference Absorption, Fluorescence and Circular Dichroism), in order to study its denaturation. An irreversible, temperature-induced, structural transition was found at around 48 degrees C. In order to establish the relative degree of hydrophobicity of tubulin aromatic residues, before and after the thermal transition, difference and fourth derivative absorption spectra at different temperatures were compared with spectra of tyrosine and tryptophan model compounds in different media. It was found that at high temperatures, tubulin acquires a partially denatured stable state, with a significant amount of residual structure still preserved. This state is characterized by a general increase of the exposure of tyrosine residues to the medium, while the environment of tryptophans becomes more hydrophobic. PMID- 1915156 TI - Selective analysis of antitumor drug interaction with living cancer cells as probed by surface-enhanced Raman spectroscopy. AB - A new technique for the selective measurement of small amounts of antitumor drugs in the nucleus and cytoplasm of a living cancer cell, based on surface-enhanced Raman spectroscopy (SERS), is proposed. The ability to detect SERS signals from very dilute (up to 10(-10) M) solutions of doxorubicin or adriamycin (DOX), and 4'O-tetrahydropyranyl-adriamycin (THP-ADM), as well as from their complexes with targets in vitro and in vivo, has been demonstrated. SERS spectra were obtained from a population as well as from single living erythroleukaemic K562 cells treated with DOX. The results of the measurements on the population of cells containing DOX in nuclei or in the cytoplasm are well correlated with the microscopic SERS measurements on the single cells treated with DOX, obtained by selectively recording signals from the living cell nucleus or from the cytoplasm. Possibilities for the application of this new technique in different aspects of cancer research are discussed. PMID- 1915155 TI - Time-dependent elastic extensional RBC deformation by micropipette aspiration: redistribution of the spectrin network? AB - The time dependence of small elastic extensional RBC deformation by micropipette aspiration has been analyzed. This process shows two-phases which are characterized by time constants of the order of some tenths of seconds and about ten seconds, respectively. The equilibrium tongue length is reached after about 30 s. For the first, fast step we assume that the membrane model of immobilized boundaries holds, i.e., the skeleton is tightly associated with the lipid bilayer and no redistribution of the skeleton with respect to the lipid bilayer is allowed. This lipid-spectrin interaction or anchorage is characterized by some association force density. It has been shown that at a given tongue length the force generated owing to the membrane deformation and acting to redistribute the spectrin, overcomes (in some membrane area) the association force density and results in an additional increase of the sucked membrane length. Equations have been derived to describe this process. From the experimental conditions of an RBC aspiration and the determined tongue length corresponding to the second slow aspiration step, the association force density between the lipid bilayer and the spectrin network may be determined. From literature data and our own results a force density of between 40 and 50 Pa has been estimated. PMID- 1915158 TI - Vibrational mode analysis of guanine by neutron inelastic scattering. AB - The low-temperature neutron inelastic spectrum of guanine has been measured. In order to assign the intense peaks observed in this spectrum, a normal mode analysis has been performed, using the Wilson GF-method. The theoretical treatment is based on a non-redundant set of internal coordinates, and a simplified valence force-field approximation. Only the fundamentals have been considered for simulating the internal vibrational mode spectrum. The calculations account for the spectral shape as well as the main observed peaks. PMID- 1915157 TI - 31P-NMR study of pig intestinal brush-border membrane structure: effect of zinc and cadmium ions. AB - 31P-NMR experiments on intact pig small intestine brush-border membrane vesicles (BBMV) and detergent-solubilized membranes gave direct insights into the organization of the phospholipids (PL) and their interaction with zinc and cadmium ions. Various endogenous PL were identified from well resolved BBM micelle spectra. These experiments revealed a strong interaction of Zn2+ and Cd2+ with the negatively charged phosphatidylinositol and phosphatidylserine. In BBM micelles, a progressive time-dependent PL degradation occurred in the absence of ions and indicated the presence of active phospholipases. The presence of zinc inhibited the degradation process whereas cadmium had the opposite influence. 31P spectra of BBMV were carefully characterized. Neither zinc nor cadmium affected the PL bilayer structural organization. A degradation of PL, monitored by the increase of the inorganic phosphate (Pi) signal, also occurred in vesicles but to a lesser extent than in micelles. A 2/3 internal, 1/3 external PL asymmetry was observed in the absence and presence of ions. PMID- 1915159 TI - Difluorophosphate as a 19F NMR probe of erythrocyte membrane potential. AB - Erythrocyte membrane potential can be estimated by measuring the transmembrane concentration (activity) distribution of a membrane-permeable ion. We present here the study of difluorophosphate (DFP) as a 19F NMR probe of membrane potential. This bicarbonate and phosphate analogue has a pKa of 3.7 +/- 0.2 (SD, n = 4) and therefore exists almost entirely as a monovalent anion at physiological pH. When it is incorporated into red cell suspensions, it gives two well resolved resonances that arise from the intra- and extracellular populations; the intracellular resonance is shifted approximately 130 Hz to higher frequency from that of the extracellular resonance. Hence the transmembrane distribution of DFP is readily assessed from a single 19F NMR spectrum and the membrane potential can be calculated using the Nernst equation. The membrane potential was independent of, DFP concentration in the range 4 to 59 mM, and haematocrit of the cell suspensions of 31.0 to 61.4%. The membrane potential determined by using DFP was 0.94 +/- 0.26 of that estimated from the transmembrane pH difference. The distribution ratios of intracellular/extracellular DFP were similar to those of the membrane potential probes, hypophosphite and trifluoroacetate. DFP was found to be transported across the membranes predominantly via the electrically-silent pathway mediated by capnophorin. Using magnetization transfer techniques, the membrane influx permeability-coefficient of cells suspended in physiological medium was determined to be 7.2 +/- 2.5 x 10(-6) cm s-1 (SD, n = 4). PMID- 1915161 TI - Intentional replantation. PMID- 1915160 TI - Molecular characterization of the human platelet integrin GPIIb/IIIa and its constituent glycoproteins. AB - Human platelet plasma membrane glycoproteins IIb (GPIIb) and IIIa (GPIIIa) form a Ca(2+)-dependent heterodimer, the integrin GPIIb/IIIa, which serves as the receptor for fibrinogen and other adhesive proteins at the surface of activated platelets. Below the critical micellar concentration of Triton X100 (TtX), the three glycoproteins do not bind appreciably to TtX and form association products of large size. The size-exclusion chromatographic patterns of GPIIb, GPIIIa and GPIIb/IIIa have been obtained at 0.2% TtX, and the molecular properties of the association products and monomer fractions have been determined by analysis of the detergent bound to the glycoproteins, laser-light scattering, sedimentation velocity, and electron microscopy (TEM). The monomer of the GPIIb-TtX complex was identified by the molecular mass (M) of the glycoprotein moiety (125 +/- 15 kDa), the molecular size (9.5 +/- 1.5 nm x 11 +/- 1.5 nm) and globular shape observed by TEM. It has a molecular mass (M*) of 197 +/- 20 kDa, a sedimentation coefficient s degrees 20* of 5.8 +/- 0.1 S, a Stokes radius R s* of 6.8 +/- 0.4 nm, and a frictional ratio f*/fmin* of 1.7 +/- 0.14. The (GPIIb)n-TtX complexes are disulphide-bonded size-heterogeneous association products of GPIIb, tetramers being the smallest species found. GPIIIa has a greater propensity to self associate than GPIIb, this tendency being lower below 1 mg GPIIIa/ml, 0.1 mM Ca2+, pH 9.0. The (GPIIIa)n-TtX complexes are noncovalent size-heterogeneous association products of GPIIIa, tetramers being the smallest form observed. The monomer of the GPIIIa-TtX complex was identified by the 103 +/- 15 kDa M determined for the glycoprotein moiety, and the 9 +/- 1.5 nm x 10 +/- 1.5 nm size and globular shape observed by TEM. It has a M* of 136 +/- 15 kDa, a s degrees 20* of 3.9 +/- 0.3 S, a Rs* of 6.4 +/- 0.5 nm, a f*/fmin* of 1.9 +/- 0.3, and, when stored at pH 7.4, has a certain tendency to form filamentous association products (20-70 nm x 2-5 nm), as observed by TEM. The GPIIb/IIIa-TtX complex in 0.2% TtX/0.1 mM Ca2+ elutes as a single monomeric fraction, as deduced from the 210 +/- 15 kDa M determined for its glycoprotein moiety and the 12 +/- 1.5 nm x 14 +/- 1.5 nm size of the globular forms observed by TEM.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915162 TI - Treatment of endodontic perforations and the potential for repair. PMID- 1915163 TI - Monitoring office sterilizers with bacterial spores. PMID- 1915164 TI - The art of masterful retreatment. 1. Post removal: obstacles to opportunities. PMID- 1915165 TI - Aggravation of penicillin-induced epilepsy in rats with locus ceruleus lesions. AB - The rate and pattern of development of seizures induced by penicillin injected intraperitoneally were determined in rats that had been depleted of brain norepinephrine (NE) by bilateral injections of the neurotoxin 6-OH dopamine into the locus ceruleus. Behavioral observations and scalp electrographic recordings were made after injection and the efficacy of NE depletion was determined by high performance liquid chromatography measurement of cortical levels of NE and its metabolites. We found that in comparison to sham-operated control rats, NE depleted rats had a significantly shorter latency to first observable myoclonic jerk, the first epileptic discharge, the first convulsion with sustained epileptic discharges, and a longer duration of convulsions. We observed a similar electrographic pattern of multifocal spikes with bilateral synchrony in both groups. However, more of the control rats (six of 12) had convulsions as compared to the lesioned rats (four of 12). These findings are consistent with previous evidence that depletion of neocortical NE facilitates the development of epileptiform activity in the CNS; however, a convulsive state was not induced by NE depletion. PMID- 1915166 TI - Anticonvulsant actions of anticholinergic drugs in soman poisoning. AB - The acute effects of the organophosphorus cholinesterase inhibitor soman include hypersecretions, convulsions, and death. The purpose of this study was to evaluate the anticholinergic compounds aprophen, atropine sulfate, azaprophen, benactyzine, benztropine, biperiden, scopolamine HBr, and trihexyphenidyl for their efficacy in preventing soman-induced hypersecretions and convulsions. Male rats were injected with the oxime HI-6 (125 mg/kg, i.p.), to increase survival time, along with various intramuscular doses of the anticholinergics 30 min prior to a dose of soman (180 micrograms/kg, s.c.; equivalent to 1.6 x the median lethal dose) that produced 100% convulsions. Signs of intoxication as well as the time-to-onset of convulsions were observed. The calculated anticonvulsant median effective dose values were 0.18, 0.33, 0.36, 0.55, 2.17, 2.30, 2.45, and 31.09 mumol/kg for scopolamine HBr, biperiden, trihexyphenidyl, benactyzine, benztropine, azaprophen, aprophen, and atropine sulfate, respectively. The same rank order of potency for inhibition of hypersecretions among these compounds was observed. Parallel studies with quaternary analogs of atropine sulfate and scopolamine HBr demonstrated, however, that these charged compounds afford no protection against soman-induced hypersecretions and convulsions. The results indicate that tertiary anticholinergic compounds afford protection against soman induced convulsions and hypersecretions and that the beneficial anticonvulsant effects are mediated through the central cholinergic system. Excitatory amino acid neurotransmitter systems may be involved in the effectiveness of these compounds. PMID- 1915167 TI - Discriminatory effect of cyclic alternating pattern in focal lesional and benign rolandic interictal spikes during sleep. AB - Twenty epileptic patients (10 male and 10 female) were polygraphically recorded during nocturnal sleep. Ten subjects, with a wide age range, were affected by focal lesional epilepsy, and 10 were children affected by benign epilepsy with rolandic spikes (BERS). In five cases a bihemispheric expression of the focal lesional bursts emerged occasionally during the night recordings. The behavior of interictal electroencephalographic (EEG) paroxysms were analyzed with respect to the two arousal states of non-rapid-eye-movement (REM) sleep: (a) the cyclic alternating pattern (CAP), expressed by biphasic EEG periodic activities and related to long-lasting fluctuations between greater (phase A) and lesser (phase B) arousal levels; and (b) the non-CAP (NCAP), manifested by EEG stationarities that reflect a sustained relative stability of arousal. The CAP/NCAP modality affected the spiking activity and distribution of the focal lesional EEG paroxysms, which appeared enhanced during CAP and which were mostly collected in phase A. The even more powerful influence of CAP and especially phase A on the secondary bisynchronous bursts suggests a crucial integration among thalamocortical circuits, arousal modulation, and epileptic generalization mechanisms. Conversely, in the BERS recordings no significant differences emerged throughout CAP and NCAP. The intense activity of the rolandic foci induced by sleep as such could be explained on the basis of the greater dependence of these functional cortical EEG abnormalities on the degree of synchronization during sleep. PMID- 1915168 TI - Scalp and limbic P3 event-related potentials in the assessment of patients with temporal lobe epilepsy. AB - Auditory oddball scalp and limbic P3s were recorded from 18 patients with unilateral temporal lobe epilepsy (TLE) prior to seizure surgery. Limbic P3s were unilaterally absent ipsilateral to the seizure focus and were present in the nonepileptogenic temporal lobe in all 18 cases studied. Scalp P3s, recorded from C3 and C4, on the other hand, were elicited bilaterally and there was no significant difference in amplitude or latency between the epileptogenic and nonepileptogenic sides. These data concur with studies of scalp P3 performed following surgery and suggest that the assessment of the contribution of limbic P3 to scalp P3 may be masked by volume conduction effects and other generators of P3. We conclude that the P3 recorded from central scalp sites, unlike its limbic counterpart, offers little clinical information in the presurgical assessment of patients with TLE. PMID- 1915169 TI - Magnetoencephalographic localization of subdural dipoles in a patient with temporal lobe epilepsy. AB - We report magnetoencephalographic localization of subdural electrode dipoles placed at the basal and mesial surfaces of the temporal lobe in a patient with temporal lobe epilepsy. The locations of the three dipoles were predicted from their magnetic fields with a computer model of the head as a conducting sphere. The predicted locations were within 1, 3, and 4 mm of the actual locations. These results, obtained in an area of the brain from which epileptiform discharges are frequently recorded, strongly support the capability of magnetoencephalography to accurately localize electrical events in this brain region. PMID- 1915170 TI - Seizure frequency in intractable partial epilepsy: a statistical analysis. AB - We examined the seizure records of 13 patients (nine men and four women, ages 27 50 years) with intractable partial epilepsy, maintained with steady anti epileptic drug dosages. Patients recorded daily seizure frequency on calendars. Periods of outpatient observation ranged from 99 to 1,710 days and the number of observed seizures ranged from 18 to over 400, with daily seizure rates of 0.1-4.3 per day. We used the quasi-likelihood regression model to examine the following four departures of the daily seizure counts from a Poisson (random) model: (1) linear increasing or decreasing time trends in expected seizure rates; (2) clustering, where the expected seizure rate on a given day depends on the number of seizures observed on the immediate prior days; (3) monthly cyclicity; and (4) increased variability (overdispersion). Linear time trends were seen in six patients (four increasing and two decreasing), clustering was seen in 10 patients, and a near-monthly cycle appeared in four patients (two of nine men and two of four women). A significant amount of extra variation (overdispersion) relative to a Poisson distribution was observed in all but one of the 13 patients. Departures from a Poisson (random) model appear more common in this population of patients with medically intractable epilepsy than is commonly recognized, and have clinical importance as well as implications for the design of clinical studies. PMID- 1915172 TI - Epileptic seizure as a presenting symptom of cerebrotendinous xanthomatosis. AB - Cerebrotendinous xanthomatosis (CTX) is a rare hereditary disease characterized by xanthomata of tendons, osteoporosis, cataracts, cerebellar ataxia, spastic paresis, and dementia. Though electroencephalographic (EEG) abnormalities are frequent in CTX, epileptic seizures have not been recognized as a major feature. A CTX patient is reported who presented with a generalized epileptic seizure and was evaluated with EEG and neuropsychological testing. Epilepsy should be considered a feature of CTX, and CTX considered as a possible, though rare, cause of symptomatic seizures. PMID- 1915171 TI - Complex partial status epilepticus provoked by ingestion of alcohol: a case report. AB - A 27-year-old man had a 5-year history of a peculiar state characterized by clouded consciousness provoked by ingestion of alcohol. The episode was identified electroclinically as nonconvulsive status epilepticus and was activated by ingestion of alcohol. Single-photon emission computed tomography (SPECT) examination during the nonconvulsive status epilepticus showed increased regional cerebral perfusion in the right frontal region. This finding, along with the EEG expressions, supports a cortical origin of the nonconvulsive status epilepticus and a diagnosis of complex partial status epilepticus (CPSE). To our knowledge, this is the first report of a documented case of CPSE during intoxication provoked by alcohol ingestion and also of a SPECT examination during CPSE. PMID- 1915173 TI - Benign partial epilepsy of childhood with monomorphic sharp waves in centrotemporal and other locations. AB - We reviewed EEGs from children whose history and clinical course was compatible with benign partial epilepsy of childhood with centrotemporal spikes. In 21% of patients with a single EEG focus, the discharge was outside the centrotemporal area. In 37.5% of patients with more than one focus, one was in the centrotemporal area while the other was not. We suggest that the typical EEG features of this syndrome are the normal background, the stereotypic morphology of the sharp waves, and their activation by drowsiness and sleep, not their exclusive location in the centrotemporal regions. Insistence on a centrotemporal location for the EEG discharges in this syndrome may lead to a misclassification of the type of epilepsy in some children with implications for therapeutic decisions and prognostic statements. PMID- 1915174 TI - Outcome for West syndrome following surgical treatment. AB - We report the case of an 18-month-old child with infantile spasms and a hypsarrhythmic electroencephalogram (EEG) pattern associated with a porencephalic cyst. Surgical removal of the cyst and its surrounding tissue was performed following failure of medical therapy. Postoperatively, the patient has been free of infantile spasms for 12 months and the EEG has normalized. He has been maintained on the same preoperative antiepileptic medications. This case suggests that surgical treatment is helpful in selected patients with infantile spasms and focal CNS lesions. PMID- 1915175 TI - Juvenile myoclonic epilepsy: factors of error involved in the diagnosis and treatment. AB - Juvenile myoclonic epilepsy (JME), a common form of idiopathic generalized epilepsy, has a distinct clinical and electroencephalographic profile. Often JME is not recognized, with serious consequences on the sufferers. We examined factors contributing to the missed diagnosis even in an epilepsy clinic. Of 70 JME patients, 66 (91.4%) were not diagnosed on referral and 22 (33%) were not initially recognized in the epilepsy clinic. The correct diagnosis was established after a mean of 8.3 +/- 5.5 years from disease onset and an interval of 17.7 +/- 10.4 months from first evaluation in the epilepsy clinic. Myoclonic jerks, the hallmark of the disease, were not usually reported by patients. Similarly, relevant questioning may not be included in the history. Absence seizures antedating jerks by many years, myoclonic jerks reported as unilateral, generalized tonic-clonic seizures occurring during sleep and focal EEG abnormalities are other factors contributing to not recognizing JME. Our study reemphasizes the need to have not only a correct seizure diagnosis but also a correct epilepsy-disease diagnosis. PMID- 1915176 TI - Eye closure sensitivity without photosensitivity in juvenile myoclonic epilepsy: polysomnographic study of electroencephalographic epileptiform discharge rates. AB - Two cases of juvenile myoclonic epilepsy (JME) presented with myoclonic jerks and EEG activation after eye closure, without sensitivity to intermittent photic stimulation. The effect of eye closure was computed by comparing discharge rates of polyspike-and-wave (PSW) complexes after eye closure and after eye opening. For one patient, never treated pharmacologically, a nocturnal polysomnograph was performed to study the variation of discharge rates of PSW complexes during wakefulness and sleep. The rate of PSW complexes was high during wakefulness before sleep onset, increased during spontaneous nocturnal awakenings, and became maximal during final morning awakening. Among nonrapid eye movement (NREM) sleep stages, EEG epileptiform activity was maximal during stages III and IV. Discharges were completely suppressed by rapid eye movement (REM) sleep. Awakenings following deep NREM sleep were very activating if no REM sleep was interposed. Awakenings from light NREM sleep were much less activating. There were no EEG abnormalities in awakenings immediately following REM sleep. Results suggest that REM sleep, similarly to eye opening, plays a role in inhibiting EEG manifestations of JME with eye closure sensitivity. PMID- 1915177 TI - Recognition impairment correlated with short bisynchronous epileptic discharges. AB - The occurrence of transitory cognitive impairment during diffuse subclinical electroencephalographic (EEG) discharges has been widely documented but the role of the parameters influencing the cognitive performance and the involvement of motor or verbal response in the tasks used is still under debate. Fifteen patients suffering from primary generalized epilepsy with frequent bisynchronous EEG epileptic bursts underwent a shape recognition task during EEG monitoring. The test sequence was as follows: memorandum, pause, and multiple choice set. After pressing the response button, the patient was asked to confirm the choice verbally. The following parameters were considered: geometrical complexity of the shape, chronological position of the burst occurring during the single test, and the duration of discharge ranging from 1 to 3 s. Results showed a significant increase in incorrect responses during the test when discharges occurred, with more errors occurring for difficult than for easy shapes. Neither the discharge position nor the duration of the epileptic burst influenced the performance. Diffuse epileptic activity of short duration produced selective effects on the cognitive process regardless of the motor component of the response. PMID- 1915178 TI - Epilepsy in children with mental retardation: a cohort study. AB - The cumulative risk of seizures and epilepsy was investigated in a prospectively identified cohort of 221 children with mental retardation (MR) born between 1951 and 1955 in Aberdeen, Scotland. By age 22 years, 33 (15%) had epilepsy. An additional 16 (7%) had had at least one seizure, but did not meet the criteria for epilepsy. The cumulative risk of epilepsy was 9, 11, 13, and 15% at 5, 10, 15, and 22 years, respectively. In children with MR and no associated disabilities, the cumulative risk of epilepsy was only 2.6, 3.2, 3.9, and 5.2% at 5, 10, 15, and 22 years. In children with MR and cerebral palsy (CP), the cumulative risk was 28, 31, and 38% at 5, 10, and 22 years. Children with a postnatal injury associated with MR had a cumulative risk of epilepsy of 53, 66, and 66% at 5, 10, and 15 years after the injury. By age 22 years, 39% had achieved 5-year seizure-free remission, including 56% of children with MR without associated disability, 47% of children with MR and CP, and 11% of children with a postnatal injury. We conclude that, in the absence of associated disability or postnatal injury, the risk of epilepsy in the retarded population is low. Epilepsy in this population also will frequently enter remission in later life. PMID- 1915179 TI - Disability pensions for epilepsy with or without mental retardation: a 15-year Swedish survey. AB - The disability pensions of the Swedish National Social Insurance Board to persons with epilepsy from January 1, 1971 to December 31, 1985 were studied. On the latter date 6,658 individuals in the register were receiving disability pensions. This corresponds to an age-specific prevalence (16-64 years) of 1.2 per 1,000. Female and male patients were about equally represented. Four diagnostic categories were specified: I: 34% with epilepsy as the main diagnosis; II: 43% with epilepsy as a complementary diagnosis; III: 4% with epilepsy as a main and mental retardation (MR) as a complementary diagnosis; and IV: 19% with MR as a main and epilepsy as a complementary diagnosis. Overall 43% had both epilepsy and MR. The crude prevalence per county ranged from 0.25 to 1.23 per 1,000. Age on entry was 1.8-63.8 (mean, 36.7) years, and pension duration was 0.1-15 (mean, 7.4) years. Mean age on prevalence day was 43.9 years. During the 15-year period annual pension costs were 20-380 million Swedish kronor (SEK) ($3-60 million), and the total costs were 2,370 million SEK ($365 million). Adjusted to 1989, the costs would be 84-463 million SEK ($13-71 million) and 4,258 million SEK ($655 million), respectively. PMID- 1915180 TI - The influence of electroencephalographic focus laterality on efficacy of carbamazepine in complex partial and secondarily generalized tonic-clonic seizures. AB - Forty-five outpatients with chronic epilepsy with complex partial seizures (CPS) alone or associated with secondarily generalized tonic-clonic seizures (SGTCS) were treated with carbamazepine (CBZ) monotherapy. All patients had only a unilateral scalp electroencephalographic (EEG) focus. Left- (n = 29) and right- (n = 16) sided foci patients were comparable for age, sex, duration, and etiology of epilepsy as well as total and free CBZ serum levels. CBZ significantly improved CPS irrespective of the side of the EEG focus, whereas SGTCS were controlled for greater than 1 year in 15 of 19 patients with left focus and in three of 11 patients with right focus. When patients with poorly controlled seizures discontinued CBZ and changed to other therapies, they achieved a significant reduction in number of SGTCS, whereas the number of CPS was unchanged. The side of EEG focus seemed to be relevant to the control of SGTCS by CBZ. Interhemispheric neurotransmitter asymmetries may be involved in the EEG focus side-dependent CBZ response. PMID- 1915181 TI - Treatment of porphyric convulsions with magnesium sulfate. AB - We report a 16-year-old girl with acute intermittent porphyria who had abdominal pain, generalized tonic-clonic and simple partial seizures, and inappropriate antidiuretic hormone secretion. Because most antiepileptic drugs are contraindicated in porphyria, she was treated with magnesium sulfate i.v. Soon after starting treatment, seizures stopped, returned, and then again responded in several trials with discontinuation and reinstitution of i.v. magnesium sulfate. Our experience encourages the use of magnesium sulfate for treatment of seizures in patients with porphyria. PMID- 1915182 TI - Clinical trials of investigational antiepileptic drugs: monotherapy designs. AB - The standard designs for safety and efficacy trials of investigational antiepileptic drugs are placebo-controlled, add-on trials and active control equivalence studies. These designs, motivated by medical ethics, have serious evidential limitations. Add-on trials are frequently criticized as insensitive and difficult to interpret in the presence of drug interactions; active control equivalence studies are not probative of test drug activity. As an alternative, we describe two trial designs: a placebo-control design with inpatients who in undergoing a presurgery seizure evaluation have had all antiepileptic drugs discontinued; and an active-control design aimed at showing the test drug superior to the control treatment, thus avoiding the interpretational difficulties of no-difference outcomes. A critical feature of these new designs is the limitation of subject exposure to unacceptable treatments. This is accomplished through protocol criteria--corresponding to therapeutic failure- which both terminate a subject's trial participation and form the basis of efficacy comparisons. PMID- 1915183 TI - Fetal rest-activity cycles and chronic exposure to antiepileptic drugs. AB - Rest-activity patterns were studied in fetuses exposed to antiepileptic drugs (AEDs) and in control fetuses at three intervals during pregnancy: 20, 32, and 38 weeks. At 20 weeks, periods of rest and activity were distinguished on the basis of fetal motility. Trunk, head, and arm movements were totaled. Periods of absence of movements for greater than 3 min were found in 20 of 31 recordings from AED-exposed fetuses compared with 11 of 20 recordings from controls (p greater than 0.05). The duration of these periods of inactivity did not differ significantly between the two groups. At 32 and 38 weeks, information on fetal motility and fetal heart rate (FHR) were combined to recognize rest-activity patterns according to the fetal behavioral state concept. At 32 weeks, three true fetal behavioral states were found for the study group, while there were none in the control group. Coincidence 1F through 4F occurred significantly less frequently at 32 weeks than at 38 weeks, regardless of whether fetuses were AED exposed or not: 59% vs. 82% for the study group and 59% vs. 80% for the controls. At 38 weeks, true fetal behavioral states appeared in 20 of 34 fetuses exposed to AEDs and in 17 of 35 controls (p greater than 0.05). The sequence in which parameters changed within state transitions was found to follow the same preferred pattern in both groups. For transitions from behavioral state 1F (quiet sleep) into 2F (active sleep) the FHR pattern changed significantly earlier than fetal body or eye movements, while for the reverse transitions the FHR pattern changed significantly later (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915186 TI - Abstracts from the annual meeting of the American Epilepsy Society. Philadelphia, Pennsylvania, December 8-11, 1991. PMID- 1915184 TI - Lack of major effects on mouse brain adenosine A1 receptors of oral carbamazepine and calcium antagonists. AB - Interaction with adenosine A1 receptors is a possible contributory mechanism to the anticonvulsant effects of carbamazepine (CBZ) and the dihydropyridine calcium antagonists. We measured the binding of [3H]cyclohexyladenosine to adenosine A1 receptors in mouse brain stem, cerebellum, and cortex after oral administration of nifedipine, nimodipine (NMD), and CBZ for 7 days and compared the results with binding in control mice. Equilibrium dissociation constant (Kd) and receptor numbers (Bmax) were calculated using Scatchard and saturation isotherm analyses. Mean Kds (SEM) in control brain stem, cerebellum, and cortex were 2.09 (0.31), 2.39 (0.2), and 3.12 (0.28) nM, respectively. Results of Bmax for the same areas were 188 (26), 280 (24), and 449 (54) fmol/mg protein. Nifedipine (p less than 0.005) and NMD (p less than 0.02) raised the Kd of A1 receptors only in the cerebellum, and CBZ increased cerebellar Bmax (p less than 0.05). These minor effects on A1 receptors in CF1 mice, when given in doses previously shown to have anticonvulsant properties in these animals, do not suggest that alteration in A1 receptor activity is an important mechanism for the anticonvulsant effects of these drugs. PMID- 1915187 TI - Air pollution and acute respiratory illness in five German communities. AB - To assess the impact of short-term exposure to air pollution on respiratory illness in children we recruited pediatricians and hospitals in five German cities to report daily counts of children's visits for croup symptoms and obstructive bronchitis. Data were collected for at least 2 years in each location. These symptoms are predominantly found in very young children, with the croup reporting peaking at 2 years of age and obstructive bronchitis at 1 year. Attacks of croup and obstructive bronchitis were relatively rare events: the mean number of cases of croup per day in each city ranged from 0.5 to 3, and obstructive bronchitis was even less frequent. A total of 6330 cases of croup and 4755 cases of obstructive bronchitis were observed during the study. The distributions of these events were quite skewed and were modeled as a Poisson process. To focus the analysis on short-term correlations and avoid seasonal confounding, biannual, annual (seasonal), and six shorter term cycles were controlled for in the regression models. After controlling for short-term weather factors, total suspended particulate matter (TSP) and nitrogen dioxide (NO2) were associated with croup cases. An increase in TSP levels from 10 micrograms/m3 to 70 micrograms/m3 was associated with a 27% increase in cases of croup; the same increase in NO2 levels resulted in a 28% increase in cases. No pollutant was associated with daily cases of obstructive bronchitis. PMID- 1915185 TI - Relationship between platelet and brain GABA transaminase inhibition by single and multiple doses of vigabatrin in rats. AB - Vigabatrin (gamma-vinyl-GABA, GVG) is an inhibitor of brain GABA transaminase (GABA-T) that also inhibits platelet GABA-T in rats and humans. We have compared the effects of single and multiple doses of GVG on both enzymes in 19 groups of 10 adult male Wistar rats, treated with increasing GVG doses (0-1,600 mg/kg/day) for 1, 8, and 28 days. The platelet GABA-T was more sensitive to the inhibitory effects of GVG than the brain enzyme was especially with low dosages of GVG. After 8 days of treatment, higher GVG plasma levels and a higher inhibition of both enzymes were shown. However, after 28 days, lower GVG plasma levels and similar inhibition of both enzymes compared to the eighth day were found. Correlations between platelet and brain GABA-T for individual rats were statistically significant after 1 day (r = 0.40, p less than 0.01) but not after 8 and 28 days of treatment because of the total inhibition of platelet GABA-T and only partial inhibition of brain GABA-T. We concluded the following: (a) platelet GABA-T is more inhibited than brain GABA-T when low doses of GVG are used and (b) multiple doses reach a higher inhibition of both enzymes than single doses, which could be explained by an increase in GVG concentrations. PMID- 1915188 TI - Spirometric abnormalities among welders. AB - A group of manual welders (N = 57) engaged in gas welding joint faces of moulded brasswares, age group 13-60 years (mean: 29.2 +/- 1.37 years), having a mean exposure period of 12.4 +/- 1.12 years (range: 1-35 years) were subjected to spirometry to evaluate the prevalence of spirometric abnormalities. The findings were compared with those obtained from a reference group (N = 131) (mean age: 31.2 +/- 1.35 years) engaged in nonwelding jobs such as packing, labelling, and transportation of the finished brassware articles. The welders showed a significantly higher prevalence of respiratory impairment (28.0%) than that observed among the unexposed controls (6.1%) (P less than 0.001), as a result of exposure to welding gases which comprised fine particles of lead, zinc, chromium, and manganese. This occurred despite the lower concentration of the pollutants at the work place. In the exposed group, the smoking welders showed a prevalence of respiratory impairment significantly higher than that observed in the nonsmoking welders (40.0 vs 18.7%) (P less than 0.10). A similar trend was observed in the control group indicating that smoking had a deteriorating effect on spirometric tests. The results of the pulmonary function tests showed a predominantly restrictive type of pulmonary impairment (12.3%) followed by a mixed ventilatory defect (8.7%) among the welders. The effect of age on pulmonary impairment was not discernible either in the exposed or unexposed group. The analysis of data in relation to duration of exposure showed significant correlation between the prevalence of respiratory abnormalities and length of exposure. Welders exposed for over 10 years showed a prevalence of respiratory abnormalities significantly higher than those exposed for less than 10 years (44.4 vs 13.3%) (P less than 0.01) thereby showing that occupational exposure to welding fumes resulted in increased prevalence of pulmonary impairment in the welders. Smoking also had a contributory role thereby suggesting an interaction between smoking and welding exposure on the prevalence of pulmonary impairment in the welders engaged in brassware industries. PMID- 1915189 TI - Mercury in the dorsal root ganglia of rats treated with inorganic or organic mercury. AB - Autometallographic silver amplification has been used to demonstrate the localization of mercury deposits in rat dorsal root ganglia after repeated intraperitoneal injections of mercuric chloride or methylmercuric chloride. The silver-enhanced mercury deposits were demonstrated with the light and electron microscope. The degree of intracellular staining of the individual cells depended on the mercury compound and total dosage. Ganglion cells (types A and B) and macrophages were found to accumulate mercury after a total dosage of 400 micrograms HgCl2. After 600 micrograms HgCl2, satellite cells, endothelial cells and fibroblasts were additionally found to contain mercury deposits. Treatment with 6000 micrograms CH3HgCl caused faint staining of type A and B ganglion cells and fibroblasts. Macrophages, however, were the most heavily stained cells after treatment with CH3HgCl. Ultrastructurally, mercury was exclusively located in lysosomes. This was irrespective of the cell type and mercury compound used for treatment. PMID- 1915190 TI - The toxicity, in vitro, of silicon carbide whiskers. AB - To mouse cells in culture, SiC whiskers (SiCW) and asbestos are similarly cytotoxic, disrupting cell membranes and killing cells. Both shorten cell generation time, increase the rate of DNA synthesis, increase total cell DNA content, and cause a loss in growth control often associated with malignant cellular transformation. Within the narrow size range of materials examined, the amount of damage appeared to be more a function of the number of whiskers present than of their size. Silicon carbide whiskers, if mishandled, may pose a serious health hazard to humans. PMID- 1915191 TI - Estimation of the allergen content of house dust samples by enzymatic assay. AB - House dust extracts contain protease and acid phosphatase activities which can be shown to be related to the content of major allergens for humans. A study of the quantitative association between measured enzyme activities and the potency of the extracts to bind IgE antibodies from the serum of house-dust-allergic patients is presented. Since major allergens from mites and other insects contributing to the allergenic potential of household dust on chemical isolation coincide with proteolytic enzymes, and since the bulk of pollen allergenic activity is related to acid phosphatase, the method presented here allows the quantitative appraisal of the contribution of the biomass of animal and plant origin to the allergenic potency of environmental dust samples without the use of human blood samples as sources of specific antibodies. PMID- 1915192 TI - Methods for integrated exposure monitoring of lead and cadmium. AB - An international pilot monitoring study on exposure to lead (Pb) and cadmium (Cd) has been implemented in Beijing, Yokohama, Stockholm, and Zagreb as part of the UNEP/WHO human exposure assessment locations (HEAL) Program. The main objective was to develop and test methods, including methods for quality assurance, for monitoring of personal exposure to Pb and Cd. The study included analytical training for Pb and Cd in blood, air filters, dust, diets, and feces, as well as exposure monitoring activities in small groups of nonsmoking women, 23-53 years of age, during 7 consecutive days. Airborne particulates, duplicate diets, feces, and blood were collected. An extensive quality assurance program was implemented in order to assure the reliability and comparability of the monitoring data. The main problem in the sample collection was associated with the air monitoring. The pumps were noisy, and the batteries had to be recharged every 6-8 hr. Collection of duplicate diets during 1 week gave good estimates of average dietary intakes of Pb and Cd. The metal contents in feces were found useful for evaluation of total peroral intakes. The methods used made it possible to demonstrate that the diet was the main source of Cd exposure at all the HEAL sites. PMID- 1915193 TI - Pharmacokinetics of the dermal route of exposure to volatile organic chemicals in water: a computer simulation model. AB - A kinetic model of dermal absorption of nonpolar organic nonelectrolytes in dilute aqueous solutions is described. The model uses systems dynamics STELLA software and is designed for a Macintosh computer. The model assumes the outer stratum corneum layer of skin to be the rate-determining barrier to dermal absorption and assumes that both stratum corneum and viable epidermal layers have storage capacity for lipophilic solutes. The model predicts between 30 and 94% of experimental results with humans under the same conditions. The degree of departure between experimental and theoretical results is inversely related to the solute's octanol/water partition coefficient, which is consistent with the most recently hypothesized mechanisms of transport of molecules across the dermal barrier. The model has potentially useful applications for risk assessment if used within its defined limits. PMID- 1915194 TI - Lysine and protein metabolism in the young lactating woman. AB - Five lactating and five postpartum non-lactating women of similar ages, times postpartum, body weight and height consumed a liquid formula diet that supplied 1.3 g protein and 32 kcal/kg per day (lactating subjects) and 1.1 g protein and 26 kcal/kg per day (non-lactating subjects). Their last meal supplied 25% of the daily intake and was consumed 4 h before they received L-[13C1]lysine (27 mumol/kg) by a single intravenous injection and L-[15N2]lysine (27 mumol/kg) orally. Frequent plasma and breath samples were collected for 6 h during which time they consumed no food. On a separate day, subjects received NaH13CO3 (10 mumol/kg) as a single intravenous dose and breath samples were collected for 6 h. Plasma tracer lysine levels were determined by gas chromatography-mass spectrometry isotope ratiometry, and breath 13CO2 levels were measured by gas isotope-ratio mass spectrometry. Averaged tracer data for the two groups were fitted to a multicompartmental model of lysine and protein metabolism that partitioned lysine kinetics between a central and two tissue compartments. The tissue compartments had characteristically fast and slow rates of lysine turnover. The results were compared with those previously obtained in nulliparous women. The postpartum state was associated with a reduction in protein turnover in a compartment with a rapid rate of protein turnover and postpartum women catabolized significantly less lysine than nulliparous controls. Lactating women catabolized slightly more lysine than the non-lactating postpartum subjects, especially when lysine catabolism was expressed as a proportion of lysine flux. Lactation was associated with smaller splanchnic and extracellular pools of free lysine and with an increase in the rate constant for absorption of orally administered lysine. Lysine flux was significantly lower in the lactating subjects and this was associated with a decrease in the rate of lysine turnover in the slowly turning over lysine compartment. The results suggest that lactation is associated with a slower rate of protein turnover in a peripheral tissue compartment. We conclude that an intake of 1.3 g protein/kg per day may be inadequate to support the protein needs of lactation and body protein metabolism and may result in metabolic adaptations that maintain lactation at the potential expense of other aspects of maternal protein turnover. PMID- 1915195 TI - A comparison of physical activity in Gambian and UK children aged 6-18 months. AB - The activity patterns of 81 Gambian and 53 UK children aged six, 12 or 18 months were compared by means of an activity diary technique. Major differences between communities were observed in the duration of play (2-3 times longer in UK compared to Gambian children) and in the duration of vigorous activities such as crawling, walking and running (2-4 times longer duration in the UK compared to the The Gambia). To investigate whether the lower activity of Gambian children could be explained by differences in nutritional or health status, subgroups of Gambian children were compared. Only small differences in activity pattern were found between Gambian children above and below 80% weight for age and between Gambian children who were or were not diagnosed ill within 10 days of study, suggesting that other factors (e.g. socio-cultural differences or the absence of conventional toys) may explain the lower activity of Gambian compared to UK children. PMID- 1915196 TI - Some regional variations in dietary patterns in a random sample of British adults. AB - Comparison was made of the reported frequency of consumption or choice of 30 food items by 8860 adults in the 11 standard regions of Great Britain, with the use of log-linear analysis to allow for the age, sex, social class and smoking habit variations between the regions. The South-East was taken as the base region against which the others were compared. The number of food items for which there were significant differences from the South-East were Scotland 23, North 25, North-West and Yorkshire/Humberside 20, Wales 19, West Midlands 15, East Midlands 10, East Anglia 8, South-West 7 and Greater London 9. Overall the findings confirm a North/South trend in relation to eating habits, even when demographic and smoking-habit variations are taken into account, with the frequent consumption of many fruit and vegetable products being much less common and of several high-fat foods (chips, processed meats and fried food) more common in Scotland, Wales and the northern part of England. In most regions there was a significantly lower frequency of consumption of fresh fruit, fruit juice, 'brown' bread, pasta/rice, poultry, skimmed/semi-skimmed milk, light desserts and nuts, and a higher consumption of red meat, fish and fried food than in the South-East. PMID- 1915197 TI - Dietary modification of Parkinson's disease. AB - To investigate the efficacy of a low-protein diet suitable for long-term use, and to observe the effect in a double-blind manner of re-introducing large neutral amino acids or an inactive placebo amino acid, eight patients with 'on-off' phenomenon were given a low-protein diet suitable for long-term use, and then the diet was supplemented with large neutral amino acids (LNAA) or placebo in a double-blind crossover trial. Five patients had improved Parkinsonian disability on a low-protein diet compared to normal diet. On supplementing the diet with LNAA or placebo, three subjects' Parkinson's disease was significantly better on placebo and there was a trend towards improvement on placebo noticed subjectively by seven patients; however, there was no overall significant difference in disability measured by mobility diaries. Thus, we have been unable to show that the improvement on a low-protein diet is due to a reduction in LNAA, rather than a placebo effect, possibly due to the paucity of subjects; however, the patients' identification of the LNAA supplement suggests that it is a genuine effect. PMID- 1915198 TI - The validity of a food use questionnaire in assessing the nutrient intake of physically active young men. AB - The validity of a self-administered food use questionnaire, comprising 122 questions on food items or dishes and designed especially to assess the intake of micronutrients, was evaluated using a 7-day food record (7DR) as a reference method. The subjects kept the food record after they filled in the questionnaire. Eighty-four male athletes participated in this study. The nutrient intake from the food use questionnaires was calculated in two ways: (i) in questionnaire 1 (FUQ-1), the portion size reported by the subjects was used, and (ii) in questionnaire 2 (FUQ-2), a 'typical' portion size was used regardless of the subject's report. In FUQ-1, the reported nutrient intake tended to be overestimated in comparison to the 7DR, whereas in FUQ-2 comparable results on a group level for all nutrients, except for proteins and fats, were obtained. The percentage of subjects similarly classified into tertiles (7DR vs. FUQ-1 or FUQ 2) varied between 37 and 54 per cent. The results show that the food use questionnaire agreed well with the food record on a group level, if a typical portion size was used. However, the agreement on an individual level was not quite as good. PMID- 1915199 TI - Palatability and intake of two commercial liquid diets in patients with poor appetite. AB - Either of two nutritionally complete liquid diets was offered prospectively for 10 consecutive days to 32 elderly patients to compare intake volume and palatability. All patients were hospitalized in a medical department and had poor appetite. The diets, which were each available in two flavours, contained either intact or partially hydrolysed proteins. They were given as sip-feeds in addition to normal food. Both products received high palatability ratings. Mean (+/- SD) volumes of intake per day were 369 (+/- 127) ml for the protein hydrolysate diet and 416 (+/- 119) ml for the intact protein diet (NS), representing approximately half of the intended intakes. There was no indication that taste fatigue developed for either of the products. PMID- 1915200 TI - Draft declaration on food, nutrition and health in Europe. Report of the Heads of the WHO Collaborating Centers on Nutrition, presented at the FENS meeting in Athens, May 1991. PMID- 1915201 TI - Discrepancy between anthropometry and biochemistry in the assessment of the nutritional status of the elderly. AB - Institutionalized aged subjects, considered free of evolutive disease and whose body weight was stable, were studied. They were divided into two groups depending on their body mass index: controls (BMI greater than or equal to 24) and depleted (BMI less than or equal to 21). The depleted group, as judged by anthropometric measurements, showed dramatically reduced body muscle and adipose masses. Usual blood parameters were normal in both groups. Biochemical markers of the protein and energy status, viz. albumin, transthyretin, transferrin, somatomedin-C, as well as serum levels of osteocalcin and apolipoproteins AI, AII, B, CII, CIII and E, were not affected in the depleted group. However, moderate iron deficiency and marked zinc deficiency were found in this group. It is concluded that in the elderly, biochemical markers of the protein and energy status are not related to the nutritional status assessed by anthropometry. PMID- 1915202 TI - Long-term effects of dietary counselling on nutrient intake and weight loss in obese children. AB - The effects of dietary counselling on food and nutrient intake and weight loss were studied over a two-year period in 32 obese children (relative weight greater than 120%) with intensive treatment (Group I) and in 16 obese children treated in a school health-care setting (Group II). The control group (Group III) comprised 29 normal-weight children (relative weight less than 120%). The children were 6 16 years old. The obese children were treated for one year and observed for another year. Food consumption data were collected by a four-day food record method. At baseline there were no differences in food consumption or nutrient intake between obese and normal-weight children. During treatment the children in Group I reduced their mean daily fat intake (P less than 0.001) and this reduction was maintained throughout the observation period. In Groups II and III no change was observed in mean daily fat intake. The relative body weight decreased by 16.2% in Group I (P less than 0.001) during the first year and the lower body weight was maintained during the observation year. No significant weight reduction was observed in Group II. The decrease in energy intake was significantly correlated with the reduction in body fat mass over the first year (rs = 0.50; P = 0.05, n = 16) in obese children passing through their pubertal growth spurt and to the reduction in relative weight over the first year (rs = 0.90; P less than 0.05, n = 5), as well as to the decrease in fat mass over the second year (rs = 0.70; P less than 0.05, n = 11) in adolescents beyond their growth spurt. In conclusion, intensive treatment resulted in decreased fat intake and also led to a reduction in relative weight, whereas a conventional approach appeared to be ineffective with regard to nutrient intake and weight loss. PMID- 1915203 TI - Urinary riboflavin and its metabolites: effects of riboflavin supplementation in healthy residents of rural Georgia (USA). AB - The following study was designed to provide a comprehensive assessment of urinary riboflavin and flavin metabolites before and after ingestion of a riboflavin load in normal human volunteers. With respect to riboflavin, the total flavin excretion, the flavin-to-creatinine ratio, and the response of the flavin catabolites to the supplement indicate a well-nourished population. Differences in the effects of supplementation on the specific flavin catabolites across sex and age groups are included in detail for the first time. The feasibility of the use of flavin catabolites for determination of riboflavin status should be tested further in individuals with clinical signs of ariboflavinosis. PMID- 1915204 TI - Enzymatic evaluation of riboflavin status of infants. AB - Riboflavin status of solely breast-fed (SBF) infants aged 1-6 months (study 1) and solely or partially breast-fed (PBF) and weaned infants aged 6-24 months (study 2) was examined by the erythrocyte glutathione reductase activation test. Maternal riboflavin status and milk riboflavin content were also measured in study 1. Riboflavin status of the infants was significantly superior to that of their mothers. However, 35 per cent of SBF infants examined suffered from biochemical riboflavin deficiency as judged by the glutathione reductase test. Supplementary feeding of 6-8-month-old infants and weaning of older infants had positive effect on riboflavin status. There was no obvious relationship between riboflavin status and anthropometric status. Milk riboflavin concentration was comparable or only slightly lower than values reported for Western women, despite marked deficiency in the mothers. PMID- 1915205 TI - Linoleic acid lowers LDL cholesterol without a proportionate displacement of saturated fatty acid. AB - We tested the specificity of the plasma cholesterol-lowering effect of linoleic acid in a comparison of linoleate-rich and saturated fatty acid-rich foods. Twelve mildly hypercholesterolemic men and women ate the two diets for three weeks each in a random cross-over design, after a two-week baseline period. A linoleic acid-rich supplement was added to the baseline diet so that the saturated and monounsaturated fatty acid content did not change significantly. Despite the consequent increase in total fat intake, the linoleate-rich diet (23 per cent energy from polyunsaturated fatty acids) significantly lowered plasma total and low-density lipoprotein (LDL) cholesterol (-8 per cent and -14 per cent respectively), while high-density lipoprotein (HDL) cholesterol rose 8 per cent. The direction of these changes was similar in all 12 subjects. Compared with a supplement that raised dietary saturated fatty acids to 30 per cent energy, the linoleate acid-rich diet gave lower total cholesterol (-14 per cent), LDL cholesterol (-18 per cent) and HDL cholesterol (-12 per cent) concentrations. Linoleic acid lowers LDL cholesterol even when saturated fatty acids are not significantly displaced and substantially more when there is such displacement. PMID- 1915206 TI - Body impedance measurements during dialysis. AB - Changes in body weight in relation to changes in body impedance were studied in six male and four female patients before and during dialysis. Before dialysis, fat-free mass from skinfolds was 46.5 +/- 6.8 kg, and total body water calculated from bio-electrical impedance was 36.9 +/- 5.2 kg. Body water expressed as a percentage of fat-free mass was calculated to be 80 +/- 4%. Mean weight loss, which was assumed to be only loss of water, was 2.7 +/- 0.7 kg. Total body impedance increased by 80 +/- 16 omega from 495 +/- 39 omega to 575 +/- 47 omega. Weight loss and increase in body impedance were highly correlated (r = -0.91, P less than 0.001). However, based on prediction formulas for total body water from bio-electrical impedance, the observed weight (water) loss should be associated with an increase in impedance of only 39 +/- 11 omega. It is concluded that the impedance value before dialysis is a relatively low value, due to the low specific resistivity of the excess of extra-cellular water in the body before dialysis. As a consequence, prediction formulas for body composition from bio electrical impedance, developed in normal hydrated subjects, overestimate body composition (total body water, fat-free mass) in subjects with oedema. PMID- 1915207 TI - Effect of socio-demographic conditions on growth of urban school children of Bangladesh. AB - The relationship between socio-demographic variables and growth of 242 school children from five schools in Dhaka city, Bangladesh, was investigated. The socio demographic data were collected by questionnaire and the anthropometric data were collected by visits to each school on a prefixed date. Children from the high family-income group showed significantly higher body weight, height, MUAC, SFT, wt/age, and ht/age compared with children from the low-family-income group. When the effect of age, sex, father's occupation and family size were adjusted for by means of multiple analysis of variance, the family income still showed a significant contribution to the variation in the anthropometric indices of these children. These findings suggest that family income makes a significant contribution as a determinant of growth of urban school children in Bangladesh. PMID- 1915208 TI - Explanatory style and cell-mediated immunity in elderly men and women. AB - Correlated pessimistic explanatory style--the belief that negative events are caused by internal, stable, and global factors--with lowered immunocompetence in a sample of 26 older adults. Two measures of cell-mediated immunity--T-helper cell/T-suppressor cell ratio and T-lymphocyte response to mitogen challenge--were lower in individuals with a pessimistic style, controlling for the influence of current health, depression, medication, recent weight change, sleep, and alcohol use. A relative increase in the percentage of T-suppressor cells seemed to underlie this immunosuppression. Although the mechanism by which explanatory style might influence immune function remains unknown, we speculate that a pessimistic style might be an important psychological risk factor--at least among older people--in the early course of certain immune-mediated diseases. PMID- 1915209 TI - Hypertension risk and caffeine's effect on cardiovascular activity during mental stress in young men. AB - Examined the cardiovascular effects of caffeine plus behavioral stress in men low versus high in risk of essential hypertension. Caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) or placebo was given on alternate days to 19 low-risk men (negative for parental hypertension and low-normal resting blood pressure, BP) and 20 high-risk men (positive history, high-normal BP). Forty minutes later, each worked for 15 min on a demanding psychomotor task during which BP, cardiac output, and vascular resistance were determined. During rest, caffeine raised vascular resistance in both groups. During the task, it supra-additively increased the systolic BP response by enhancing the rise in cardiac output, producing equivalent BP rises in both groups. Due to the higher resting pressures of the high-risk men, caffeine plus the task resulted in 50% of these having transient BP of 140/90 mg Hg or greater. Caffeine in combination with mental stress may produce undesirable BP in those at risk for hypertension. PMID- 1915210 TI - Question-induced cognitive biases in reports of dietary intake by college men and women. AB - In two experiments, investigated how variations in questionnaire structure influence respondents' reports of two aspects of dietary intake--the frequency with which various food items are eaten and the sizes of the portions that are eaten. In Experiment 1, approximately 400 subjects, prior to making a frequency judgment, were asked to think either about a specific occasion or about all the occasions on which they had eaten a particular food. The thoughts that preceded the frequency judgment influenced that judgment: Thinking of the range of occasions on which a food is consumed resulted in higher frequency estimates than thinking only of the most recent occasion. In Experiment 2, the same subjects made judgments about their typical portion sizes of several foods relative to described standards. For only one of eight foods were estimates properly and significantly affected by differences among the described standards. These results suggest that respondents are not particularly sensitive to portion-size definitions. We consider the implications of these phenomena for the development of a general theory of the cognitive processes that subserve health-survey responding. PMID- 1915211 TI - Social support networks among families of children with craniofacial anomalies. AB - Investigated the social support available to families of children born with craniofacial anomalies and the perceived degree of satisfaction derived from these relationships. Thirty-six children (1 month to 5 years old) born with craniofacial deformities (FD) were matched by age and sex to 36 children with no significant physical or behavioral problems. The Social Support Questionnaire Revised, the Revised Denver Developmental Screening Test, and a semistructured interview were administered. Results indicated that parents of FD children reported less available social support and were significantly less satisfied with their support. Parents of children who had more severe physical impairments and were rated as less attractive reported having less available and less satisfying social support. In particular, the social competence of the child was the most important predictor of parental social support. This result is interesting as the parents of FD children appeared to underreport the presence of behavioral psychological problems in their children. PMID- 1915212 TI - Psychological side effects of breast cancer screening. AB - Evaluated the impact of receiving abnormal mammogram results on women's anxiety and breast cancer worries and on their breast self-examination (BSE) frequency and intentions to obtain subsequent mammograms. A telephone survey was conducted with 308 women 50 years old and older approximately 3 months following a screening mammogram. Subjects included women with suspicious abnormal mammograms, nonsuspicious abnormal mammograms, and normal mammograms. Women with suspicious abnormal mammograms exhibited significantly elevated levels of mammography related anxiety and breast cancer worries that interfered with their moods and functioning, despite the fact that diagnostic work-ups had ruled out breast cancer. Women with moderate levels of impairment in mood or functioning were more likely to practice monthly BSE than women with either high or low levels of impairment. Breast cancer worries, perceived susceptibility to breast cancer, and physician encouragement to get mammograms all exhibited independent positive relationships to mammogram intentions. PMID- 1915213 TI - Symptom schemata in chronic respiratory patients. AB - In view of evidence that illness prognoses and adaptive functioning may be influenced by the accuracy of people's knowledge about their physical symptoms, the present study extended these findings to the chronic care population. It was hypothesized that individuals hold beliefs and develop theories about their physical symptoms and that the accuracy of these beliefs is predictive of the individuals' general level of adaptive functioning. A modified version of an instrument designed to measure the accuracy of illness schemata was employed with a sample of 31 chronic respiratory patients. Accuracy rating correlated positively and significantly with ratings of adaptive functioning, whereas no relationship was observed between adaptive functioning and severity of the patients' medical condition. Well-informed patients functioned at a higher level physically, psychologically, and socially than less-informed patients. These findings point to the importance of patient education for prognosis. Possible mediating factors are discussed. PMID- 1915214 TI - Prevalence of dieting among working men and women: the healthy worker project. AB - Examined dieting to lose weight in a population of 2,107 men and 2,540 women employed in 32 worksites in the upper Midwest. Lifetime prevalence of this behavior was estimated to be 47% in men and 75% in women, and point prevalence was reported as 13% and 25% in men and women, respectively. Lifetime prevalence of participation in organized weight-loss programs was 6% in men and 31% in women; current prevalence was 1% in men and 6% in women. The strongest correlate of dieting behavior was relative body weight. In logistic regression analyses, dieting tended to be associated positively with education and occupational status and, in men only, was more prevalent among those with a history of hypertension. Dieters reported lower food intakes than nondieters, but the two groups did not differ consistently in reported physical activity. Overall, dieting appears to be a pervasive behavioral U.S. phenomenon that may contribute in part to population differences in the prevalence of obesity. PMID- 1915215 TI - Parental cigarette smoking and cognitive performance of children. AB - A prior study identified a relationship between parental cigarette smoking and cognitive performance by adolescent children who did not smoke. That study was stimulated by the reasoning that environmental smoke might influence performance through oxygen deprivation. The present study, using longitudinal data from the Child Health and Development Studies (1987), extended the earlier research by controlling for mother's prenatal smoking and other potentially confounding variables and by examining four different measures of cognitive performance. The findings indicate that the relationship between parental smoking and at least one of the cognitive measures persists with controls and that there is a dose response relationship between parental smoking and cognitive performance. Findings are discussed in the context of mechanisms that might explain the association between parental smoking and child cognition. PMID- 1915216 TI - Measuring medical and nursing students' attitudes toward AIDS. AB - Investigated attitudes toward AIDS patients among medical and nursing students. Two separate cohorts of students (total N = 550) were surveyed to examine and then validate with confirmatory factor analysis the latent factor structure of such attitudes. Results indicate that a three-factor structure representing fear of contagion, negative emotions, and professional resistance provides a good fit to the data (goodness-of-fit index [GFI] = .92, parsimonious GFI = .67). We offer the resulting 15-item AIDS Attitudes Scale (AAS) as a reliable and valid measure for assessing health care students' attitudes toward working with AIDS patients. Our results suggest the presence of multiple predictors of such attitudes. PMID- 1915217 TI - Use of carbon monoxide breath validation in assessing exposure to cigarette smoke in a worksite population. AB - Assessed the usefulness of carbon monoxide (CO) breath validation of self reported smoking status in a large worksite population (N = 4,647). CO assessment was performed as part of a baseline survey procedure. CO levels differed substantially in relation to self-reported smoking status and amount smoked. Correcting for ambient exposure (estimated by mean CO levels among never smokers) produced more satisfactory results than uncorrected CO levels. Striking company differences were observed in mean CO exposures among self-reported never smokers. An unexpected finding was that 17.1% of current smokers reported smoking less than daily. Although the CO measure was excellent in detecting moderate and heavy smokers, it was inadequate in detecting occasional and light smokers. If detection of occasional or lighter smoking is critical to the purposes of the study, the more expensive (but more accurate) cotinine measure is preferred. PMID- 1915218 TI - A rational approach to lameness and its prevention--at last? PMID- 1915219 TI - Laminitis research. PMID- 1915220 TI - The epidemiology and possible MHC linkage of culicoides hypersensitivity. PMID- 1915221 TI - Laminitis in the pony: conservative treatment vs dorsal hoof wall resection. AB - The clinical and radiographic findings in 21 ponies with laminitis and its treatment and results are described. All ponies received non-steroidal anti inflammatory drugs. All were fed hay and no concentrates. They were box rested for varying periods depending on clinical improvement. Dorsal hoof wall resection was performed in 11 ponies and all regained complete soundness. To shorten the period of non-activity, working ponies were shod and the hoof wall defect was packed with technovit or a combination of glue with cotton cuttings. Ten were treated conservatively; two recovered completely, four remained lame and four were killed because of recurrent laminitis. PMID- 1915222 TI - Prevalence of serum precipitating antibodies in horses to fungal and thermophilic actinomycete antigens: effects of environmental challenge. AB - Sera from 54 two- to three-year-old Thoroughbred horses from an English racing stable were examined for precipitins to antigen extracts prepared from 18 species of moulds (fungi and thermophilic actinomycetes) isolated from the same stable. Twenty-seven horses exhibited serum precipitins to one or more antigens; sixteen of the mould antigens elicited positive reactions in sera from one or more horses. Significantly more precipitins occurred in sera of those horses stabled in a barn than among those stabled in individual boxes. This indicated a possible association between type of housing, level of exposure to airborne moulds and presence of serum precipitins. None of the horses had overt respiratory disease. This study agrees with reports of the presence of serum precipitating antibodies to mould antigens in clinically healthy horses and confirms that serological tests, therefore, are of little value in the diagnosis of chronic obstructive pulmonary disease (COPD) or 'heaves'. PMID- 1915223 TI - Pulmonary gas exchange correlated to clinical signs and lung pathology in horses with chronic bronchiolitis. AB - Eight horses (mean weight 438 kg) with chronic obstructive pulmonary disease (COPD) were studied for clinical signs, ventilation/perfusion relationships (VA/Q) and lung morphology. Four horses were killed and necropsied after the study. In horses with COPD, minute ventilation was almost twice as high as normal, whereas PaO2 was significantly decreased. Cardiac output was normal, but pulmonary artery pressure and pulmonary vascular resistance were significantly increased. The VA/Q distribution was abnormal with an increased scatter of VA/Q ratios. However, shunt (VA/Q = 0) was increased in one horse only. Ventilation of dead space and high VA/Q regions (VA/Q greater than 10) were increased markedly and comprised 74 per cent of minute ventilation. On lung biopsy, all horses showed chronic bronchiolitis with epithelial hyperplasia and metaplasia. Diffuse acinar hyperinflation also was evident at necropsy. There was a significant inverse correlation between the respiratory rate and the fractional ventilation of normal VA/Q regions. Also, there was a significant agreement between the extent of bronchiolar epithelial hyperplasia in necropsy specimens of lungs and the degree of ventilation of high VA/Q regions and dead space. The findings suggest that hyperinflation of the lung due to obstructed airways may be the common denominator of increased ventilation of high VA/Q regions and dead space ventilation and of elevated pulmonary artery pressure in horses with COPD from chronic bronchiolitis. PMID- 1915224 TI - Evaluation of transabdominal ultrasound-guided amniocentesis in the late gestational mare. AB - Serial transabdominal amniocentesis was performed on eight mares in late gestation. Ultrasonography was used to identify the two placental fluid sacs and the foetus. A biopsy guide attached to the transducer allowed visualisation of the needle path during insertion. Amniotic fluid was obtained in 85 per cent of the attempts, although as mares approached parturition substantial pools of amniotic fluid were more difficult to locate. Two mares aborted during the study probably because of complications of the procedures, whereas six mares produced normal foals at term. The abortions preclude clinical use of this technique currently. However, there was sufficient success in retrieval of amniotic fluid and outcome of pregnancies to continue the study of amniocentesis in larger groups of mares to determine the clinical and research value of this technique. PMID- 1915225 TI - Identification of subclinical tendon injury from ground reaction force analysis. AB - In this study a method of analysing ground reaction forces was developed to help in the diagnosis of subclinical flexor tendon injury. A Kistler force plate was used to obtain records from a population of Thoroughbreds in National Hunt training over a period of two years. Characteristic features of the force patterns generated were measured and shown to have low variance, both between horses and over a period of two racing seasons in animals that were sound throughout the trial. Specific changes in the loading pattern of the limb, which correlated with injury of the superficial digital flexor tendon, were identified from horses that sustained clinical injury during the study. Retrospective analysis showed that changes became apparent in the force patterns before this group of horses exhibited clinical lameness. This type of analysis provides an objective means of detecting tendon injury at an early stage. PMID- 1915226 TI - A comparison of two techniques for arthrocentesis of the equine metacarpophalangeal joint. AB - Because arthrocentesis of the metacarpophalangeal joint through the proximal palmar pouch may induce synovial haemorrhage, this study evaluated arthrocentesis through the lateral collateral sesamoidean ligament. The proximal palmar pouch and collateral sesamoidean ligament approaches were used in contralateral forelimbs to obtain paired initial synovial fluid samples from 16 horses 12 to 15 h before being killed. Synovial fluid samples also were collected from the same joints at necropsy and the subcutis, synovium and articular cartilage were evaluated. Metacarpophalangeal joint arthrocentesis through the collateral seamoidean ligament yielded fewer haemorrhagic synovial fluid samples with less subcutaneous and synovial inflammation, and also yielded 2 ml of synovial fluid more often than arthrocentesis through the proximal palmar pouch. PMID- 1915227 TI - Use of DNA fingerprinting in paternity analysis of closely-related Exmoor ponies. AB - DNA fingerprinting techniques were used to try to resolve the parentage of an Exmoor pony foal. Three young Exmoor ponies, one female and two males, shared a paddock and the female subsequently became pregnant. The two possible sires were three-quarter siblings and were also half-siblings to the dam. Southern hybridisation of Exmoor pony DNA with human mini-satellite probes resolved the disputed parentage in spite of the fact that there was a 70 per cent band share between the individuals involved. Colt M6 was 2.06 times more likely to be the father than an uncle, and Colt M3 was 477 times more likely to be an uncle than the father. PMID- 1915228 TI - Pharmacokinetic, biochemical and tolerance studies on carprofen in the horse. AB - Carprofen, a non-steroidal anti-inflammatory drug (NSAID) was administered to three Thoroughbred geldings and three Shetland ponies to determine its plasma disposition and tolerance. The main pharmacokinetic characteristics of carprofen in horses and ponies were a volume of distribution of 0.08 to 0.32 litres/kg (mean +/- se = 0.23 +/- 0.04) a systemic clearance of 26.4 to 78.5 ml/min (mean +/- se = 44.9 +/- 8.0) and a plasma elimination half-life of 14.5 to 31.4 h (mean +/- se = 21.9 +/- 2.3). There was no evidence of any accumulation of carprofen in plasma when the drug was given orally at a dose rate of 0.7 mg/kg for 14 consecutive days. Carprofen was well tolerated following intravenous (iv) and oral administration. Intramuscular (im) administration resulted in elevated levels of plasma creatine kinase suggesting muscle cell damage. According to the results of this study carprofen can be regarded as a long-acting NSAID in horses from a pharmacokinetic point of view. Either iv, im or the oral route of administration could be used to achieve high carprofen plasma concentrations. PMID- 1915229 TI - Ultrasonographic evaluation of fetlock annular ligament constriction in the horse. AB - The diagnosis of restriction of free movement of the flexor tendons through the fetlock canal usually rests on the characteristic clinical appearance of this condition, or airtendography. In a series of seven normal Warmblood horses and 16 diseased horses of various breeds, the efficacy of ultrasonography in the diagnosis of this condition was determined. In normal limbs, the annular ligament is a very thin structure usually not visible on sonograms. In diseased limbs, ultrasonography outlined flexor tendon injury, distension and thickening of the digital sheath, peritendovaginal tissue proliferation and thickening of the annular ligament. Four different types of constriction syndrome were noticed. The first type (nine cases), was characterised by thickening of the annular ligament and distension of the digital sheath; the second type (three cases) was dominated by distension of the digital sheath; the third type (three cases) was characterised by superficial digital flexor tendon injury and thickening of the annular ligament and in the fourth type (one case), the constriction resulted from distension of the digital sheath and extensive peritendovaginal tissue proliferation. PMID- 1915230 TI - Fusion of the distal intertarsal and tarsometatarsal joints in the horse using intraarticular sodium monoiodoacetate. AB - Six normal horses received 3 intra-articular injections of sodium monoiodoacetate (MIA) in the distal intertarsal (DIT) and tarsometatarsal (TMT) joints of one hindlimb. Injections were at three week intervals, and post injection pain was controlled with routine administration of phenylbutazone for five days following each injection. All horses underwent a gradually increasing exercise programme consisting of walking and trotting beginning one week after the first injection and continuing for 24 weeks. All treated joints showed increasingly severe radiographic evidence of degenerative joint disease with time. Clinical signs were mild or absent during exercise. All treated joints showed radiographic and histological evidence of fusion 24 weeks after the first injection. Amount of radiographic fusion ranged from 54.49 per cent to 88.64 per cent of the joint space. Histologically, the joint space that appeared radiographically fused was filled mainly with woven and lamellar bone. Fibrocartilage and fibrous tissue was seen frequently in the transition between fused and unfused areas. Articular cartilage in unfused areas was thin, fibrillated, hypocellular and histochemically showed diminished proteoglycan content. Existing joint space was filled with fibrin and necrotic, acellular chondroid matrix. We conclude that MIA will produce fusion of the DIT and TMT joints of normal horses in 24 weeks, and may offer a relatively easy, inexpensive and non-invasive treatment for distal tarsal osteoarthritis in the horse. PMID- 1915231 TI - An epidemiological study of summer eczema in Icelandic horses in Norway. AB - A survey of summer eczema was conducted on 391 Icelandic horses in Norway. The study showed a prevalence of summer eczema of 17.6 per cent in the horses investigated. Icelandic horses born in Norway where shown to be less affected with summer eczema than imported horses, 8.2 per cent and 26.9 per cent respectively (P less than 0.001). There was no difference in the prevalence of summer eczema relative to gender or colour of the horse. The number of horses affected with summer eczema rose with increasing age and the number of years which had elapsed since importation. On average, Icelandic horses born in Norway developed summer eczema at the age of 5.3 years. The onset of disease for imported horses was, on average, 4.1 years after importation. The study also revealed that a significantly greater number of horses imported from Iceland to Norway during the period October to April, which has a minimal or low activity of insects (32.3 per cent), had developed summer eczema, compared with horses imported during the period May to September, when insects are more active (16.7 per cent), (P = 0.044). Horses with summer eczema were shown to be significantly more affected by respiratory disease than non-affected horses (P = 0.0086). The most common sites and clinical signs of summer eczema are also described. PMID- 1915232 TI - Distribution of leucocyte antigens in Icelandic horses affected with summer eczema compared to non-affected horses. AB - Three hundred and three horses, exported from Iceland to Norway, Sweden, Denmark, Switzerland or Germany were tested for their distribution of leucocyte antigens. One hundred and thirty-six horses were affected with summer eczema. The panel of sera recognised the internationally accepted ELA-specificities A 1 to A10, and the nine work shop specificities W 11 to W 15 and W 18 to W 21. Also, some local specificities, characterised in Switzerland (Be I, Be III, Be 8, Be 25, Be 26, Be 27), and two non major histocompatibility complex (MHC)-linked antigens (Ely 1:1, Ely 2) were included. Only one antigen, Be 8, gave a statistically significant difference in distribution between the two populations: Relative risk = 2.5, x2 = 10.11, corrected P less than 0.01. PMID- 1915233 TI - Whole blood re-calcification time in equine colic. AB - Whole blood re-calcification times were evaluated as a measure of endotoxin associated coagulopathy in horses. First, the effects of endotoxin concentration and duration of in vitro incubation of citrated whole blood with endotoxin on the whole blood re-calcification time of blood collected from healthy horses were determined. Increasing concentrations or incubation times of endotoxin accelerated the whole blood re-calcification time. This effect was attributed mainly to increased monocyte thromboplastin activity. Second, whole blood re calcification time, a clotting profile, plasma factor VII activity and plasma endotoxin concentration on blood samples obtained from 35 equine colic patients and 10 healthy horses were determined. Compared with healthy horses, colic patients had a longer mean whole blood re-calcification and prothrombin time, lower per cent factor VII activity and higher mean fibrin degradation products concentration. Within the colic patient group, horses that did not survive had detectable endotoxin in plasma, longer whole blood re-calcification and prothrombin times, and lower plasma factor VII activity, compared with colic patients that survived. These data indicate that colic patients with endotoxaemia experience hypercoagulable states, followed by consumptive coagulopathy. Although the cause of endotoxin-associated coagulopathy is likely multi-factorial, increased expression of monocyte thromboplastin activity may be involved in the pathogenesis of coagulopathy. The whole blood recalcification time is a simple, fast and inexpensive way to detect coagulopathy during endotoxaemia and determine the prognosis for survival. PMID- 1915235 TI - Radiographic technique for the pelvis in the standing horse. PMID- 1915234 TI - Changes in some haematological and metabolic indices in young horses during the first year of jump-training. AB - Effects of an 18 min exercise test, on three separate occasions during a one year jump-training programme, was studied in seven horses. Determinations were carried out on venous blood for packed cell volume, haemoglobin, total protein, lactate and pyruvate, glucose, free fatty acids, insulin, glucagon, blood gases, bicarbonate, pH, aldolase, aspartate aminotransferase and alanine amino transferase. Exercise caused a slight increase in lactate and pyruvate, total protein, aldolase, alanine aminotransferase, pO2, bicarbonate and pH. Glucose, free fatty acids and pCO2 levels decreased. Training caused no significant difference in these changes. However, during the year, increases in lactate and decreases in pH (resting levels) were observed. PMID- 1915236 TI - Sarcocystis neurona cultured in vitro from a horse with equine protozoal myelitis. PMID- 1915237 TI - Critical pulmonary stenosis in a newborn foal. PMID- 1915238 TI - Paper symposium: Biomedical applications of two-dimensional gel electrophoresis. PMID- 1915240 TI - A practicable two-dimensional electrophoresis of urinary proteins as a useful tool in medical diagnosis. AB - Practical experience with a rapid two-dimensional electrophoresis technique for routine analysis of urinary proteins is discussed. The method consists of cellulose acetate electrophoresis in combination with sodium dodecyl sulfate (SDS) electrophoresis, performed together with Coomassie Blue gel staining on "PhastSystem". Over 400 analyses were performed within the time of two years. Most patients were from nephrological, urological and kidney-transplant departments. Some of them were from obstetric, pediatric or oncological departments. A systematic discussion and evaluation of the two-dimensional protein pattern with typical examples is outlined. PMID- 1915239 TI - The simplified technique of high resolution two-dimensional polyacrylamide gel electrophoresis: biomedical applications in health and disease. AB - The application of our simplified technique of high resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to human body fluids is reviewed. Serum/plasma protein changes associated with alcohol abuse, familial dyslipoproteinemia ("fish-eye" disease), and myocardial infarction are demonstrated. High resolution 2-D PAGE of amniotic fluid, cerebrospinal fluid, urine, and saliva is shown with reference to the work of others, and the detection of pink-violet staining "lumicarmines" in sweat and tear fluid is reported for the first time. General aspects relating to the methodology are discussed. These include sample preparation, the choice of electrophoresis conditions (denaturing or nondenaturing) and detection method (Coomassie Brilliant Blue or silver), and the effects of native protein pretreatment with sodium dodecyl sulfate prior to silver staining or isoelectric focusing gel shrinkage in glycerol prior to second-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. PMID- 1915242 TI - The identification of proliferation and tumour-induced proteins in human endothelial cells: a possible target for tumour therapy. AB - The continued growth and spread of tumours is dependent on the proliferation of the endothelial cells of their vasculature. The presence of proliferation- or tumour-induced surface proteins on these endothelial cells would offer a suitable epitope for monoclonal antibody therapy of tumours. Using cultured human umbilical and capillary endothelial cells, we have stimulated them with simple mitogens and tumour conditioned media and examined the proteins induced by [35S]methionine incorporation and 125I-surface-labelling. Two-dimensional polyacrylamide gel electrophoresis revealed the induction of proliferation and tumour-related antigens on the surface of the endothelial cells. Subsequent monoclonal antibody studies suggest that tumour specific surface proteins are present on most tumour endothelium. PMID- 1915241 TI - Analysis of cerebrospinal fluid from patients with psychiatric and neurological disorders by two-dimensional electrophoresis: identification of disease associated polypeptides as fibrin fragments. AB - Two-dimensional electrophoresis (2-DE) of cerebrospinal fluid (CSF) samples--from 347 patients with various psychiatric and neurological disorders--and subsequent silver staining revealed two additional polypeptides (Mr 40,000) in 49% of 111 schizophrenics, 46% of 43 schizoaffective patients, 36% of 41 patients with affective disorders, 43% of 28 patients with multiple sclerosis, but not in 25 patients without neurological symptomatology, nor in 9 patients with Lues, and in only 2 of 25 patients with AIDS. The two polypeptides, as detected by 2-DE, eluted after size exclusion chromatography in fractions containing proteins with Mr greater than 200,000. After 2-DE of CSF samples, enriched by gel chromatography, the polypeptides were immobilized by blotting onto glass-fiber membranes and subjected to N-terminal sequencing. Polypeptide A was identified as beta-chain remnant (beta 2), derived from plasmin cleavage of fibrin(ogen). After size exclusion chromatography, 2-DE, and Western blotting, polypeptide A and B, as well as several other spots, reacted with fibrinogen antibodies, suggesting that the polypeptides are subunits of a fibrin degradation complex. PMID- 1915243 TI - Two-dimensional polyacrylamide gel electrophoresis of human lung cancer: qualitative aspects of tissue preparation in relation to histopathology. AB - It is of great importance to identify new objective markers significant for the diagnosis, treatment, and prognosis of human cancers. Cytometric assessment of the DNA content has been shown to be one parameter which correlates excellently with the clinical course of patients with solid cancers of the breast, prostate, and thyroid. However, additional specific marker polypeptides are needed in order to further improve the diagnostic and prognostic sensitivity. Two-dimensional polyacrylamide gel electrophoresis (2-DE) is a unique tool in this field of cancer research, but serious problems concerning intersample variations in the 2 DE pattern must be solved because quantitative variations of potential marker polypeptides are expected to occur at low levels. In this study we examined a modified preparation method for tumor tissues, focusing on the relation between histopathological properties and 2-DE gel quality. We selected a group of human lung cancers sharing similar prognosis; nevertheless, the 2-DE patterns showed significant intersample but low intrasample variations. It is concluded that histopathological features, such as a local homogeneity, and the amounts of connective tissue and serum proteins are critical factors for the successful preparation and high quality of 2-DE-gels. PMID- 1915244 TI - Nuclear and DNA-binding proteins in human brain tumors. AB - Nuclear proteins obtained from human brain tumor cell lines by differential salt extraction were subjected to high-resolution two-dimensional electrophoresis. Several hundred spots were detectable in the low salt (0.4 M NaCl) extract using silver staining. These patterns exhibited remarkable differences between the different cell lines we analyzed. A less complex pattern occurred when nuclei were subsequently treated with high salt (2.5 M NaCl/5 M urea). We compared the electropherograms from various human glioblastoma cell lines and found them very similar and even a high degree of similarity occurs between glioblastomas and other human tumor cell lines. Beside these more general observations we detected several proteins at least enriched in human glioblastomas which were totally absent in low grade astrocytomas and nonglial tumors. They could be separated from the bulk of nonspecific proteins by simple modifications of the isoelectric focusing conditions. From these results we conclude that nuclear proteins obtained by sequential salt extraction and separated by two-dimensional techniques may provide tumor specific proteins suitable for antibody production. PMID- 1915245 TI - Molecular profiles of the cell membrane bound and cytoplasmic forms of the human MHC class-II associated invariant polypeptides. AB - Several sub-types of histocompatibility class-II molecules are known to exist, including DR, DQ and DP, each subset organized in alpha and beta heterodimers. These molecules play a central role in immunorecognition via direct noncovalent binding of degraded nonself immunogenic peptides followed by ligand-interaction with T cells. In the cytoplasm the class-II alpha and beta chains associate, in addition with a third backbone molecule known as the invariant chain. In this study we show that all class-II subsets associate with the invariant chain probably from the same pool and that a subset of invariant chain is expressed as a cell surface subunit. This sub-unit, whose function is still unknown, was detected by flow-cytometry and by two-dimensional gel analysis followed by antibody-mediated immunoprecipitations. PMID- 1915246 TI - Biochemical characterization by two-dimensional electrophoresis of lymphocyte antigens involved in cell-to-cell or cell-to-matrix adhesion. AB - We have exemplified three cases of application of two-dimensional (2-D) electrophoresis to the characterization of lymphocyte membrane antigens. We could show that the proteins recognized by two monoclonal antibodies, LAK1 and LAK2, on the surface of large granular cells mediating natural- and lymphokine-activated killing are distinct molecules. LAK1 is expressed without any structural modification, even on the surface of endothelial cells. Another membrane antigen, recognized by the monoclonal antibody FB12, was shown to have the overall structure of the integrins of the very late activation (VLA) class, being composed of an alpha and of a beta subunit. The latter corresponded to the beta 1 type as already characterized for other VLAs, whereas the alpha chain was different from alpha 1 through alpha 6. The 2-D protocol using immobilized pH gradients for the first dimension allows reliable assessment of the identity of individual components because of the reproducibility of the absolute coordinates for spot position. PMID- 1915247 TI - A comparative analysis of alterations in protein expression after activation or human immunodeficiency virus, type 1 infection of human CD4+ T cells. AB - We have previously described an in vitro model for studying human immunodeficiency virus, type 1 (HIV-1) infection in CD4+ T cells [1]. This model employs the WE17/10 cell line, which loses expression of its T cell receptor/CD3 (TCR/CD3) after several months of productive infection. We have used this model to analyze the synthesis and posttranslational modification of viral and cellular proteins after HIV-1 infection and to determine the relationship of these changes to TCR/CD3 expression. Mainly we observe positive changes in protein expression after infection. A phosphoprotein, referred to as WH:1, appears in infected cells that still express their TCR/CD3 complex, and its persistence is linked to the presence of the complex. We examined whether loss of the TCR/CD3 complex could be associated with alterations in the T cell activation pathway as a result of infection. We used T cell activators and inhibitors to determine whether there were common elements between the two events. Quantitative enhancement in one spot, Cs:1, occurred after both Cyclosporin A treatment of uninfected cells and HIV-1 infection of untreated cells. Taken altogether, these data suggest that a correlation exists between negative regulation of late events in the T cell activation pathway and down regulation of the TCR/CD3 complex after HIV-1 infection. PMID- 1915248 TI - Global analysis of lymphocyte gene expression: perturbation of H-9 cells by infection with distinct isolates of human immunodeficiency virus--an exposition by multivariate analysis of a host-parasite interface. AB - AIDS is a progressive disease associated with steady loss of helper T cells and several other functions. As the disease evolves, cytopathogenic human immunodeficiency (HIV) variants of increasing virulence can be isolated from the host. The HIV is an unusually variable genome by virtue of a low replication fidelity. In this report we describe our effort to test the hypothesis that there is a correlation between virus variability and cytopathogenicity, and further, that there is an "impact" of the virus infection on the expression of host cellular genes. To search for such a relationship, we infected H-9 cells (human CD4+ lymphoblastoid cell line) with each of 5 isolates of HIV of distinct origin and cytopathogenicity. To measure the influence of the virus infection on the expression of host cellular genes, shortly after infection, (3 h or 13 h), cells were radiolabeled and the radioactive polypeptides separated by two-dimensional gel electrophoresis. Radiofluorographs were prepared and analyzed to determine relative rates of biosynthesis of cellular polypeptides. To organize the large amounts of data found, cluster analysis and principal component analysis were used to expose the data in formats that allowed a model construction. The rates of biosynthesis of many cellular polypeptides were altered upon viral infection in terms of both enhancements and impairment of biosynthesis. Some of the variation in polypeptide synthesis was isolate-specific, while most alterations were of modest magnitude. There appears to be no "overall effect" associated with infection by a cytopathic variant of the virus. Polypeptides affected by the cytopathic variants were determined as targets for further investigation. The method used promotes the measurement of "ensemble" information that is characteristic of the process and it promotes the creation of models of virus action. PMID- 1915249 TI - A study of protein synthesis in cells cultured from involved psoriatic skin. AB - Using histochemical techniques an abnormal programme of epidermal differentiation has been well documented in psoriasis. In order to characterise further the biochemistry of this process we have cultured dermal fibroblasts and epidermal keratinocytes from involved psoriatic skin. This has facilitated metabolic radiolabelling of skin cells and analysis of protein synthesis by two-dimensional polyacrylamide gel electrophoresis. The expression of keratin and differentiation markers was identical to that of normal keratinocytes, suggesting that psoriatic epidermal differentiation is not truncated in vitro as has been postulated to be the case in vivo. Low molecular mass components (5-8.5 kDa), previously shown to be upregulated in suprabasal keratinocytes, were detected in epidermal fractions from psoriatic skin enriched for basal cells. Of special interest was a component of 26 kDa, pI 5.9, which was highly upregulated in psoriatic as compared to normal cultured keratinocytes and was not detected in fibroblasts. These findings are in accord with a qualitatively abnormal pattern of differentiation for keratinocytes in the involved psoriatic epidermis. PMID- 1915250 TI - An improved method combining two electrophoretic procedures: application to the separation of lens alpha-crystallin isoforms. AB - Polypeptides having different net electric charges and very similar molecular weights, visualized as one single band in sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS-PAGE), can be readily analyzed by an improved method combining two electrophoretic procedures. The methodology consists of the identification and isolation of selected protein bands from SDS-PAGE, their equilibration in an isoelectric focusing (IEF) sample buffer, and their casting and separation in an IEF flat-bed gel. This method requires no extra equipment, is highly reproducible, is suitable for quantitative and comparative studies, and is especially useful in the case of small samples. As a particular example, we analyze here the subunit composition of alpha-crystallins of young and embryonic quail lenses. PMID- 1915251 TI - The application of two-dimensional polyacrylamide gel electrophoresis to medical microbiology: molecular epidemiology of viruses and bacteria. AB - A variety of molecular methods can be used to identify protein and nucleic acid markers with which to investigate the epidemiology of viruses and bacteria. This paper reviews the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) for studying microbial molecular epidemiology. A small format 2-D PAGE system is described for locating protein markers in group B coxsackie viruses (CVB) and Haemophilus influenzae isolates. Representative isolates of CVB serotypes 2, 4, and 5 were compared by analysing the intracellular proteins present in CVB-infected HEp-2 cells by 2-D PAGE protein gels. Although some of the virus-induced proteins had similar electrophoretic mobilities, the three serotypes could be distinguished from each other on the basis of a major virus-induced protein of molecular weight between 39,000 and 43,000. Protein differences were demonstrated among six serotype 2 CVB (CVB-2) isolates. Four clinical CVB-2 isolates collected over a period of four months had indistinguishable two-dimensional protein profiles. Comparison of the two dimensional protein profiles of cloned virus stocks prepared from a single clinical CVB isolate demonstrated that it was a heterogeneous virus population. The proteins of nontypable and type-b H. influenzae isolates were compared. Up to 160 proteins, detected by staining with Coomassie Brilliant Blue R, were resolved by 2-D PAGE. Although protein differences between individual bacterial isolates were detected, comparable two-dimensional protein profiles were found for the two groups of H. influenzae isolates. There was no similarity in the two-dimensional protein profiles of H. influenzae and Aeromonas. Potential protein markers were identified that may be useful in long-term studies of H. influenzae epidemiology. PMID- 1915252 TI - Why is the driver rarely motion sick? The role of controllability in motion sickness. AB - The central hypothesis of the work is that the dimension of control-no control plays an important role in motion sickness. Although it is generally agreed that having control over a moving vehicle greatly reduces the likelihood of motion sickness, few studies have addressed this issue directly, and the theoretical explanation for this phenomenon is not completely clear. In this study, we equated groups differing in controllability for head movement, vision, activity, and predictability, which have often been suggested in the literature as explanations for the driver's immunity to motion sickness. Twenty-two pairs of yoked subjects were exposed to nauseogenic rotation. One subject of each pair had control over the rotation and head movements, while the other was exposed passively to the same motion stimulus. Subjects who had control reported significantly fewer motion sickness symptoms and less of a decrement in their well-being, as compared to the yoked subject without control. The results are discussed in relation to Reason's sensory rearrangement theory and the concept of feed-forward mechanisms in motion perception. PMID- 1915253 TI - Hand strength: the influence of grip span and grip type. AB - The maximal force from each of the fingers II-V (FF) and the resultant force between the jaws of the tool (RF), due to contribution from all fingers, were measured using a pair of modified pairs. The RF was measured at 21 handle separations and the FF was measured at seven handle separations for each finger. A traditional grip type was compared with a 'reversed' grip where the little finger was closest to the head of the tool. Sixteen subjects (8 females and 8 males) participated in the study. Both the RF and FF varied according to the distance between the handles. For both grip types, the highest RF was obtained at a handle separation of 50-60 mm for females and 55-65 mm for males. For wide handle separations, the RF was reduced by 10% (cm increase in handle separation). The force-producing ability of the hand was influenced by the grip type and the highest RF was obtained when using the traditional grip. An interaction was found between the fingers, i.e., the maximal force of one finger depended not only on its own grip span, but also on the grip spans of the other fingers. About 35% of the sex difference in hand strength was due to hand size differences. PMID- 1915254 TI - The insulation provided by infants' bedclothes. AB - The insulation provided by bedclothes of given thermal resistance (tog value) depends on the size of the body insulated. For simple shapes, discs, strips and cylinders, it is always less than the tog value. If the trunk and limbs of a baby are considered to be thermally independent cylinders, each with the bedclothes well tucked in, the net insulation, I, in tog units, is described by (1/I) = 0.6/Ib + 0.3/Im + 4.5/G, where Ib is the tog value of the bedclothes, Im that of the mattress and G the girth of the trunk in centimetres. I is reduced if the cot is small, if occupation has been belief, and if the bedclothes are loosely draped over the baby. I is increased (perhaps 2.5 times) if the baby curls up tightly. It is concluded that there is little risk of overinsulating a normal baby whose posture is not restricted, but a combination of fever and thick bedclothes might be dangerous. PMID- 1915255 TI - Acceptable weights and physiological costs of performing combined manual handling tasks in restricted postures. AB - Eight healthy, male underground coal miners (mean age = 36.9 yrs +/- 4.5 SD) participated in a study examining psychophysically acceptable weights and physiological costs of performing combined lifting and lowering tasks in restricted head-room conditions. Independent variables included posture (stooping or kneeling on two knees), task symmetry (symmetric or asymmetric), and vertical lift distance (35 cm or 60 cm). All tasks were 10 min in duration and were performed under a 1.22 m ceiling to restrict the subject's posture. Subjects were required to raise and lower a lifting box every 10s, and asked to adjust the box weight to the maximum amount they could handle without undue strain or fatigue. During the final 5 min of each test, data were collected to determine the energy expenditure requirements of the task. Results of this study demonstrated that psychophysical lifting capacity averaged 11.3% lower when kneeling as compared to stooping. Subjects selected 3.5% more weight in asymmetric tasks, and lifted 5.0% less weight to the 60 cm shelf compared to the 35 cm shelf. Heart rate was not significantly affected by posture, but was increased an average of 4 beats/min in asymmetric conditions, and by 3.5 beats/min while lifting/lowering to/from the high shelf. Oxygen uptake was increased by 9% when stooped, by 10% when lifting/lowering asymmetrically, and by 8.2% when performing the task to the high shelf. Results of this study indicate that, wherever possible, materials that must be lifted manually in low-seam coal mines be designed in accordance with the decreased lifting capacity exhibited in the kneeling posture. PMID- 1915256 TI - An electromyographic study of dental work. AB - Musculoskeletal disorders are common among dentists, and have been ascribed to the demands of high precision work and sustained static loading in the neck shoulder region, combined with a flexed and rotated cervical spine. In order to determine muscular load levels during dentistry, activity in neck, shoulder, and arm muscles was recorded using an electromyography technique (EMG). Normalized mean, median, 10th and 90th percentile EMG amplitude levels (% maximal reference contraction, %max-RVC) were calculated during ordinary dental work. Among the muscles investigated, the trapezius muscle on both sides had the highest mean (the right trapezius 9.0% and the left 7.6% of max-RVC) and 10th percentile amplitude levels (both about 2% of max-RVC). The trapezius muscles showed similar myoelectric activity on the right and left side, probably because of similar muscular static load on the both sides. The right extensor carpi radialis muscle had a significantly higher muscular load level than the left one, possibly due to stabilization demands on the dominant wrist during demanding precision work. The infraspinatus muscle had low activity level on both sides, reflecting that the dentists worked with a small degree of arm elevation and external rotation. The dentistry work thus seems to generate relatively high muscular load on both trapezius and dominant extensor-carpi-radialis, and relatively low load on the infraspinatus muscle. PMID- 1915257 TI - Paul Branton 1916-1990. PMID- 1915259 TI - Theoretical and functional analysis of the SIV fusion peptide. AB - The fusion domain of simian immunodeficiency virus (SIV) envelope glycoproteins is a hydrophobic region located at the amino-terminal extremity of the transmembrane protein (gp32). Assuming an alpha helical structure for the SIV fusogenic domain of gp32 in a lipid environment, theoretical studies have predicted that the fusion peptide would insert obliquely in the lipid bilayer. This oblique insertion could be an initial step of the fusion process by disorganizing locally the structure of the lipid bilayer. We have tested this hypothesis by selectively mutagenizing the SIV gp160 expressed via a vaccinia virus vector, to alter the theoretical angle of insertion of the fusion peptide. The fusogenic activity of the wild-type and mutant glycoproteins was tested after infection of T4 lymphocytic cell lines by the recombinant vaccinia virus, and measure of syncytia formation. Mutations that modified the oblique orientation reduced the fusogenic activity. In contrast, mutations that conserve the oblique orientation did not alter the fusogenic properties. Our results support the hypothesis that oblique orientation is important for fusogenic activity. PMID- 1915258 TI - Identification of 3- and 4-repeat tau isoforms within the PHF in Alzheimer's disease. AB - The microtubule associated protein tau is incorporated into the pronase resistant core of the paired helical filament (PHF) in such a way that the repeat region is protected from proteases, but can be released as a major 12 kDa species from the PHF core by formic acid treatment and by boiling in SDS. This fragment retains the ability to aggregate in the presence of SDS. Detailed sequence analysis of the 12 kDa species shows that it consists of a mixture of peptides derived from the repeat region of 3- and 4-repeat tau isoforms comigrating as a single electrophoretic band. However, the 4-repeat isoforms released from the core lack either the first or the last repeat. The pronase-protected region of tau within the PHF core is therefore restricted to three repeats, regardless of isoform. The alignment of cleavage sites at homologous positions within tandem repeats after protease treatment indicates that the tau-core association is precisely constrained by the tandem repeat structure of the tau molecule. PMID- 1915260 TI - Electrostatic destabilization of the cytochrome b6f complex in the thylakoid membrane. AB - Three of the membrane-spanning polypeptides of the chloroplast cytochrome (cyt) b6f complex were sequentially released from the thylakoid membrane, in the order cyt b6, suIV and Rieske iron-sulfur protein, as the pH was increased from 10 to 12, a protocol usually employed to remove peripheral proteins from membranes. The fourth polypeptide of the cyt b6f complex, cyt f, which spans the membrane once, was apparently not released. The pH values for half-release at low ionic strength were approximately 10.7, 11.1 and 11.3 respectively. The separation of the polypeptides of the complex and the sequential release is readily seen at pH 11, where the loss from the membrane of cyt b6, suIV and Fe iron-sulfur center is approximately 90%, 50% and 20%, respectively. the release of cyt b6 from the membrane was reflected by the absence of its characteristic reduced minus oxidized absorbance signal. The pH values at which the release occurred increased as the ionic strength was raised, implying that the release of the b6f polypeptides arises from extrusion due to repulsive electrostatic interactions probably caused by deprotonation of tyrosine and lysine residues. The lipid content of the released polypeptides was very low, consistent with the observation of a non-membranous state. It is proposed that the pH-dependent extrusion requires two electrostatic effects at alkaline pH higher than approximately 10.5: (i) increased electrostatic repulsion between neighbouring polypeptides of the complex, arising from increased net negative charge in the peripheral segments of these polypeptides, which can cause separation of the polypeptides from the complex; and (ii) ionization of residues such as tyrosine in the membrane-spanning alpha-helices, and neutralization of residues such as lysine which can bind to the negative membrane surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915261 TI - Protein targeting towards the thylakoid lumen of chloroplasts: proper localization of fusion proteins is only observed in vivo. AB - Routeing of fusion proteins to the thylakoid lumen of the chloroplast was compared in vitro and in vivo. The Escherichia coli protein beta-lactamase was used as a passenger to study this intraorganellar sorting process. The first step, translocation of beta-lactamase into the chloroplast stroma, occurs properly both in vitro and in vivo and is dependent on the presence of a transit peptide in the protein construct. The second step, targeting towards the thylakoid lumen, is more complicated as was also observed previously when other passenger proteins were used. In vitro, the presence of a thylakoid transfer domain is not enough for routeing and proper processing. Only when the complete thylakoid lumen precursor plastocyanin was fused to beta-lactamase was the fusion protein processed adequately, but routeing was still incomplete. However, in vivo, the information present in the thylakoid transfer domain was the only requirement for proper transport towards the thylakoid lumen. These data show that in vivo, the only requirement for targeting of passenger proteins towards the thylakoid lumen is the presence of a transit peptide and a thylakoid transfer domain. Furthermore, we demonstrate that the in vitro import system does not necessarily reflect the in vivo situation with respect to intraorganellar sorting. PMID- 1915262 TI - Decoding signals for membrane protein assembly using alkaline phosphatase fusions. AB - We have used genetic methods to investigate the role of the different domains of a bacterial cytoplasmic membrane protein, MalF, in determining its topology. This was done by analyzing the effects of MalF topology of deleting various domains of the protein using MalF-alkaline phosphatase fusion proteins. Our results show that the cytoplasmic domains of the protein are the pre-eminent topogenic signals. These domains contain information that determines their cytoplasmic location and, thus, the orientation of the membrane spanning segments surrounding them. Periplasmic domains do not appear to have equivalent information specifying their location and membrane spanning segments do not contain information defining their orientation in the membrane. The strength of cytoplasmic domains as topogenic signals varies, correlated with the density of positively charged amino acids within them. PMID- 1915263 TI - Role of potentially charged transmembrane residues in targeting proteins for retention and degradation within the endoplasmic reticulum. AB - The selective breakdown of newly synthesized proteins retained within the endoplasmic reticulum (ER) is probably mediated by the specific recognition of structural features of protein substrates by components of a degradative system. Within the alpha chain of the multisubunit T-cell antigen receptor (TCR) complex, a transmembrane sequence containing two basic amino acid residues has been shown to act as a determinant for retention and rapid degradation in the ER. We now demonstrate that single basic or acidic amino acid residues can cause targeting for retention and degradation in the ER when placed within the transmembrane domain of an integral membrane protein normally destined for the cell surface. The effect of such potentially charged residues is dependent on their relative position within the transmembrane sequence and on the nature of the amino acid side chains. The phenotypic changes induced by potentially charged transmembrane residues occur without apparent alterations of the global folding or transmembrane topology of the mutant proteins. These observations test the hypothesis that potentially charged residues within transmembrane domains can provide the basis for a motif for ER degradation and explain the selective breakdown of some proteins retained within the ER. PMID- 1915264 TI - Novel genes for potential ligand-binding proteins in subregions of the olfactory mucosa. AB - Odorant detection is specifically mediated via receptor neurons in the olfactory mucosa but is a complex process involving a number of different cell types producing proteins of differing function. We have used the technique of subtractive hybridization cDNA cloning to identify novel genes expressed exclusively in the olfactory mucosa which may play a role in olfaction. Ten distinct groups of cDNA clones were identified which corresponded to mRNA transcripts highly expressed in rat olfactory mucosa but undetectable in thymus, kidney, lung, brain, spleen and liver. Some of these clones identify substructures in the mucosal tissue for which no other probes are currently available. Others identify novel mRNA species in the Bowman's glands. The predicted proteins for three of these clones are homologous to proteins which bind to either lipopolysaccharides (RYA3 and RY2G5) or to polychlorinated biphenyls (RYD5). In addition, while RYA3 and RY2G5 are highly homologous, they appear to be expressed in different parts of the mucosal tissue. The sequence homologies and subanatomical location of expression suggest that these proteins might interact with odorants before or after specific recognition by odorant receptors. Therefore, the olfactory mucosa may possess diverse, functionally distinct odorant-binding proteins which recognize and bind separate classes of odorants. PMID- 1915265 TI - Identification of the second subunit of the murine interleukin-5 receptor: interleukin-3 receptor-like protein, AIC2B is a component of the high affinity interleukin-5 receptor. AB - Murine interleukin-5 (IL-5) binds to its receptor with high and low affinity. It has been shown that the high affinity IL-5 receptor (IL-5-R) is composed of at least two membrane protein subunits and is responsible for IL-5-mediated signal transduction. One subunit of the high affinity IL-5-R is a 60 kDa membrane protein (p60 IL-5-R) whose cDNA was isolated using the anti-IL-5-R monoclonal antibody (mAb), H7. This subunit alone binds IL-5 with low affinity. The second subunit does not bind IL-5 by itself, and is expressed not only on IL-5-dependent cell lines but also on an IL-3-dependent cell line, FDC-P1. Expression of the p60 IL-5-R cDNA in FDC-P1 cells, which do not bind IL-5, reconstituted the high affinity IL-5-R. We have characterized the second subunit of the IL-5-R by using another anti-IL-5-R mAb, R52.120, and the anti-IL-3-R mAb, anti-Aic-2. The anti Aic-2 mAb down-regulated binding of IL-5 to an IL-5-dependent cell line, Y16. Both R52.120 and anti-Aic-2 mAbs recognized membrane proteins of 130-140 kDa expressed on FDC-P1 and Y16 cells. The R52.120 mAb recognized both murine IL-3-R (AIC2A) and its homologue (AIC2B) expressed on L cells transfected with suitable cDNAs. The high affinity IL-5-R was reconstituted on an L cell transfectant co expressing AIC2B and p60 IL-5-R, whereas only the low affinity IL-5-R was detected on a transfectant co-expressing AIC2A and p60 IL-5-R.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915266 TI - Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. AB - Leukemia inhibitory factor (LIF) is a cytokine with a broad range of activities that in many cases parallel those of interleukin-6 (IL-6) although LIF and IL-6 appear to be structurally unrelated. A cDNA clone encoding the human LIF receptor was isolated by expression screening of a human placental cDNA library. The LIF receptor is related to the gp130 'signal-transducing' component of the IL-6 receptor and to the G-CSF receptor, with the transmembrane and cytoplasmic regions of the LIF receptor and gp130 being most closely related. This relationship suggests a common signal transduction pathway for the two receptors and may help to explain similar biological effects of the two ligands. Murine cDNAs encoding soluble LIF receptors were isolated by cross-hybridization and share 70% amino acid sequence identity to the human sequence. PMID- 1915267 TI - p53 is frequently mutated in Burkitt's lymphoma cell lines. AB - A panel of 12 Burkitt's lymphoma cell lines and four other B cell lines were tested for the presence of mutations in p53. Protein analysis using a mutant specific antibody and sequencing of both cDNA and genomic DNA revealed changes relative to the standard p53 protein sequence in 12 of the 16 lines studied, including 10 of the BL lines. Mutation of p53 in the BL lines was usually accompanied by loss of the other allele of p53. Testing of the mutated p53 cDNAs for gain of transforming activity or loss of growth suppression activity showed that several of the BL mutants were functionally altered from wild-type p53. PMID- 1915268 TI - The plant oncogene rolC is responsible for the release of cytokinins from glucoside conjugates. AB - The rolC gene of Agrobacterium rhizogenes, which drastically affects growth and development of transgenic plants, codes for a cytokinin-beta-glucosidase. Indeed, rolC protein expressed in Escherichia coli as a fusion protein hydrolyses cytokinin glucosides, thus liberating free cytokinins. Furthermore, beta glucosidase activity present in E. coli extracts expressing the rolC protein was inhibited by affinity-purified antibodies specific for the rolC protein. Finally, rolC proteins expressed in transgenic plants were shown to be responsible for cytokinin-beta-glucosidase activity. Morphological and phytohormonal analysis, performed on transgenic plants that are somatic mosaics for the expression of the rolC gene, extend and confirm our interpretation that the developmental, physiological and morphological alterations caused by rolC expression in transgenic plants are primarily due to a modification of the cytokinin balance. These observations shed new light on the control of growth and differentiation in plants by growth factors. PMID- 1915269 TI - The GTPase stimulatory activities of the neurofibromatosis type 1 and the yeast IRA2 proteins are inhibited by arachidonic acid. AB - Three proteins, GTPase activating protein (GAP), neurofibromatosis 1 (NF1) and the yeast inhibitory regulator of the RAS-cAMP pathway (IRA2), have the ability to stimulate the GTPase activity of Ras proteins from higher animals or yeast. Previous studies indicate that certain lipids are able to inhibit this activity associated with the mammalian GAP protein. Inhibition of GAP would be expected to biologically activate Ras protein. In these studies arachidonic acid is shown also to inhibit the activity of the catalytic fragments of the other two proteins, mammalian NF1 and the yeast IRA2 proteins. In addition, phosphatidic acid (containing arachidonic and stearic acid) was inhibitory for the catalytic fragment of NF1 protein, but did not inhibit the catalytic fragments of GAP or IRA2 proteins. These observations emphasize the biochemical similarity of these proteins and provide support for the suggestion that lipids might play an important role in their biological control, and therefore also in the control of Ras activity and cellular proliferation. PMID- 1915270 TI - Casein kinase II induces c-fos expression via the serum response element pathway and p67SRF phosphorylation in living fibroblasts. AB - Elevation of intracellular casein kinase II (CKII) levels through microinjection of purified CKII results in the rapid and transient induction of c-fos in quiescent rat embryo fibroblasts, and activation of quiescent cells by serum is accompanied by the nuclear relocation of endogenous CKII. The induction of c-fos by CKII is inhibited by coinjection of oligonucleotides corresponding to the sequence of the serum response element (SRE) present in the c-fos promoter, indicating that competitive displacement of positive factors from the endogenous c-fos SRE prevents c-fos induction by CKII. Furthermore, the expression of c-fos induced by either CKII injection or serum activation is also inhibited by microinjection of antibodies against the 67 kDa serum response factor (p67SRF) indicating the absolute requirement of p67SRF in this process. Finally, we show the specific phosphorylation of p67SRF in vivo following microinjection of CKII into quiescent cells. Together, these data strongly support that CKII induces c fos expression through binding/activation of the phosphorylated p67SRF at the SRE sequence. PMID- 1915271 TI - Poliovirus proteinase 3C converts an active form of transcription factor IIIC to an inactive form: a mechanism for inhibition of host cell polymerase III transcription by poliovirus. AB - In HeLa cells, RNA polymerase III (pol III)-mediated transcription is severely inhibited by poliovirus infection. This is due primarily to a reduction in the transcriptional activity of TFIIIC, a transcription factor which binds in a sequence specific manner to the internal promoter of pol III genes. Using gel retardation assays, we have shown previously that inhibition of pol III transcription by poliovirus is correlated with disappearance of a transcriptionally active form of TFIIIC (complex I) concomitant with the appearance of a faster mobility, transcriptionally inactive form of TFIIIC (complex III). We show here that a poliovirus with a point mutation in the proteinase 3C (3Cpro) region failed to produce complex III and is limited in its ability to inhibit pol III transcription compared with the wild-type virus. Incubation of purified 3Cpro, expressed in Escherichia coli, with transcriptionally active TFIIIC (complex I) in vitro resulted in generation of the transcriptionally inactive complex III form of TFIIIC. In an in vitro transcription assay, treatment of the complex I form of TFIIIC with 3Cpro almost completely inhibited pol III transcription. Finally expression of the 3Cpro gene in transfected HeLa cells resulted in significant inhibition of pol III-mediated transcription. The results presented here suggest that proteolysis of the transcriptionally active form of TFIIIC by poliovirus 3Cpro is a mechanism by which poliovirus inhibits host cell RNA pol III transcription. PMID- 1915273 TI - Effects of retinoic acid excess on expression of Hox-2.9 and Krox-20 and on morphological segmentation in the hindbrain of mouse embryos. AB - Mouse embryos were exposed to maternally administered RA on day 8.0 or day 7 3/4 of development, i.e. at or just before the differentiation of the cranial neural plate, and before the start of segmentation. On day 9.0, the RA-treated embryos had a shorter preotic hindbrain than the controls and clear rhombomeric segmentation was absent. These morphological effects were correlated with alterations in the spatiotemporal distribution patterns of two genes, Hox-2.9 and Krox-20, which are expressed in the otic and preotic hindbrain and in specific neural crest cell populations. Hox-2.9 was expressed throughout the preotic hindbrain region, instead of being confined to rhombomere 4. Krox-20 was not expressed rostral to the Hox-2.9 domain, i.e. its normal rhombomere 3 domain was absent. The Hox-2.9/Krox-20 boundary was ill-defined, with patches of alternating expression of the two genes. In migrating neural crest cells, Hox-2.9 expression was both abnormally extensive and abnormally prolonged. Neural crest cells expressing Krox-20 remained close to the neural tube. Embryos exposed to RA on day 8 1/4 appeared to be morphologically normal. We suggest that early events leading to rhombomeric segmentation and rhombomere-specific gene expression are specifically vulnerable to raised RA levels, and may require RA levels lower than those in the region of somitic segmentation. PMID- 1915274 TI - The oct3 gene, a gene for an embryonic transcription factor, is controlled by a retinoic acid repressible enhancer. AB - Oct3 is an embryonic octamer-binding transcription factor, whose expression is rapidly repressed by retinoic acid (RA). In this report, we have determined the transcriptional control region of the oct3 gene and studied the mechanism of the RA-mediated repression. The chromosomal oct3 gene consists of five exons. Three subdomains of the POU region and transactivating domain are located in separate exons. Transcription initiates at multiple sites in the GC-rich region lacking a typical TATA box. The upstream 2 kb region can confer the cell type-specific expression and RA-mediated repression. Analysis of the upstream region by deletion mutagenesis locates a cis element (RARE1) which functions as a stem cell specific, yet RA-repressible, enhancer. Footprint and gel-retardation assays show that RARE1 is composed of two domains, each of which is recognized by distinct factors. Microinjection of oct3-lacZ constructs into fertilized eggs indicates that RARE1 can function in early embryos. We suggest that RARE1 is a critical cis element for oct3 gene expression in embryonic stem cells and for the RA-mediated repression. PMID- 1915272 TI - Transcriptional activation by heterodimers of the achaete-scute and daughterless gene products of Drosophila. AB - The achaete-scute complex (AS-C) and the daughterless (da) genes encode helix loop-helix proteins which have been shown to interact in vivo and to be required for neurogenesis. We show in vitro that heterodimers of three AS-C products with DA bind DNA strongly, whereas DA homodimers bind weakly and homo or heterocombinations of AS-C products not at all. Proteins unable to dimerize did not bind DNA. Target sequences for the heterodimers were found in the promoters of the hunchback and the achaete genes. Using sequences of the former we show that the DNA binding results obtained in vitro fully correlate with the ability of different combinations to activate the expression of a reporter gene in yeast. Embryos deficient for the lethal of scute gene fail to activate hunchback in some neural lineages in a pattern consistent with the lack of a member of a multigene family. PMID- 1915275 TI - POU proteins bend DNA via the POU-specific domain. AB - POU proteins constitute a family of ubiquitous as well as cell type-specific transcription factors that share the conserved POU DNA binding domain. This domain consists of two distinct subdomains, a POU-specific domain and a POU homeodomain, that are both required for high affinity sequence-specific DNA binding. In a circular permutation assay, several POU proteins, including Oct-1, Oct-2A, Oct-6 and Pit-1, demonstrated a position dependent mobility of the protein-DNA complexes, suggesting induction of DNA bending. This was confirmed by detection of relative bend direction, using pre-bent DNA, and by enhanced ligase mediated cyclization. Bending was caused by interaction with the POU domain. By contrast, binding of the POU homeodomain did not distort the DNA structure, indicating that the POU-specific domain confers DNA bending. PMID- 1915276 TI - A negatively acting DNA sequence element mediates phytochrome-directed repression of phyA gene transcription. AB - Phytochrome represses transcription of its own phyA genes within 5 min of light triggered conversion to its active Pfr form. We have utilized microprojectile mediated gene transfer into etiolated rice seedlings to delineate sequence elements in the oat phyA3 promoter responsible for this regulation. Linker-scan mutagenesis of this promoter has identified two positive elements which together are necessary for maximal transcription in the absence of Pfr. These elements are designated PE1, centered at position -357 bp, and PE3, centered at position -96 bp. Sequence mutagenesis immediately downstream of PE3 results in maximal transcription in the presence of high Pfr levels, indicating that Pfr represses phyA3 transcription through a negatively acting sequence element. This element, designated RE1, with the sequence CATGGGCGCGG, encompasses a motif that is highly conserved in all monocot phyA promoters thus far characterized. DNase I protection analysis indicates that oat nuclear extracts contain multiple factors that bind to an array of sequence motifs, including PE1 and part of PE3, within 400 bp upstream of the oat phyA3 transcription start site. This DNA-binding pattern is not altered by Pfr. Weak binding to part of the RE1 motif is evident but also with no difference between high and low Pfr levels. We conclude that the signal transduction chain that mediates Pfr-directed repression of phyA3 transcription terminates with a negatively acting transcription factor that binds to the sequence element RE1. PMID- 1915277 TI - A novel switch-activating site (SAS1) and its cognate binding factor (SAP1) required for efficient mat1 switching in Schizosaccharomyces pombe. AB - The pattern of parental DNA strand inheritance at the mating type locus (mat1) determines the pattern of mat1 switching in a cell lineage by regulating the formation of the site-specific double-stranded break (DSB) required for mating type interconversion in Schizosaccharomyces pombe. To study the molecular basis of this programmable cell type change, we conducted structural and functional analyses of the DNA sequence flanking the DSB at mat1. We have identified and characterized a DNA-binding activity that interacts with a specific sequence located 140 bp from the DSB site. Deletion analysis of DNA sequences located distal to mat1 cassette revealed the presence of at least two switch-activating sites (SAS1 and SAS2), both of which are required for generating an efficient level of DSBs and consequently, for efficient switching. We found that SAS1 overlaps with the target site of the DNA-binding activity called SAP1 (for switch activating protein). Point mutations generated in the SAS1 element that adversely affect binding of SAP1 protein in vitro were found to reduce the efficiency of switching in vivo, suggesting the requirement of SAP1 for switching. Pedigree analysis revealed that SAS1 is equally required for initial switching (one switch in four grand-daughters of a cell) and for consecutive switching (where the sister of a recently switched cell switches again), indicating that the two developmentally asymmetric cell divisions required to generate a particular pattern of switching share the same molecular control mechanism. PMID- 1915278 TI - Nucleosomes are positioned with base pair precision adjacent to the alpha 2 operator in Saccharomyces cerevisiae. AB - Analysis of the chromatin structure of minichromosomes containing the binding site for the yeast alpha 2 repressor protein by indirect end-labeling has previously indicated that nucleosomes are stably positioned over sequences adjacent to the alpha 2 operator in the presence of the repressor. Development of a primer extension assay for nucleosome position now allows a more detailed examination of the location of these nucleosomes relative to the operator sequence, and indicates that nucleosomes are precisely and stably positioned both translationally and rotationally over sequences adjoining the operator. In addition, this assay enables analysis of the chromatin structure of single copy, genomic sequences. Chromatin structures determined for two genes regulated by alpha 2, STE6 and BAR1, are consistent with nucleosomes precisely positioned downstream of the operator sequence, incorporating promoter elements, in alpha cells but not in a-cells. The location of these nucleosomes relative to the operator sequence is highly analogous to that observed in the minichromosome. The stability of the nucleosomes adjacent to the operator together with the precision of their location suggests that they may play a role in repression of a specific gene expression by alpha 2. Further, the primer extension assay allows a comparison of the structure of these positioned nucleosomes formed in vivo to that previously described for core particles reconstituted in vitro. PMID- 1915279 TI - DNA-dependent phosphorylation of histone H2A.X during nucleosome assembly in Xenopus laevis oocytes: involvement of protein phosphorylation in nucleosome spacing. AB - ATP is required for physiological nucleosome alignment in chromatin reconstituted from high-speed nuclear supernatants of Xenopus laevis oocytes. Here we show that during in vitro nucleosome assembly the histone variant H2A.X becomes phosphorylated upon transfer onto DNA, a process which is also observed in vivo. Histone H2A.X phosphorylation increases in the early phase of the assembly reaction, reaching a steady state after approximately 16 min and is maintained with a half-life of the phosphate groups of approximately 2 h. After 6 h, the overall phosphorylation state of H2A.X is reduced, indicating that the phosphorylation-dephosphorylation ratio decreases considerably over time. Addition of alkaline phosphatase leads to a persistently lowered state of H2A.X phosphorylation, in contrast to other nuclear phosphoproteins which undergo rapid rephosphorylation. This suggests that H2A.X phosphorylation is a unique step in the histone-to-DNA transfer process. Selective inhibition of DNA-dependent phosphorylation of H2A.X and of other proteins causes a loss of the physiological 180 bp spacing. PMID- 1915280 TI - Expression of the replication protein Arp of phasyl shows dual regulation by an antisense promoter. AB - Phasyl is the smallest naturally occurring replicon found so far in Escherichia coli. It encodes a protein which is essential for autonomous replication (Arp). The transcriptional start of the arp gene was mapped. A strong antisense promoter was found in close proximity to the arp promoter. The inactivation of this promoter led in cis to a strong increase of the transcription of the arp gene and to the inactivation of autonomous replication of phasyl. The product of the antisense promoter is an 83 nt RNA molecule, which is not translated. The antisense RNA led in trans to the inhibition of the translation of the arp mRNA, presumably mediated by the formation of an RNA-RNA hybrid in which the Shine Dalgarno sequence of the arp transcript is sequestered. The expression of the arp gene is thus controlled by two negatively acting mechanisms: it is subject to a transcriptional control in cis exerted by the antisense promoter and to a translational control in trans mediated by the antisense RNA. Inactivation of one mechanism of control cannot be compensated by the remaining one. PMID- 1915282 TI - In vitro translation of Plasmodium falciparum aldolase is not initiated at an unusual site. AB - It has been proposed recently that translation of fructose-1,6-diphosphate aldolase of the malaria parasite Plasmodium falciparum is initiated at a UAG codon, both in the parasite and in a rabbit reticulocyte cell-free translation system. We have introduced mutations around that UAG codon and find that cell free expression of a construct encoding an AUG in this position results in a slightly larger translation product. The translation product of the construct encoding the UAG codon is of the same apparent molecular weight as the products obtained from two other constructs; one in which the UAG is replaced by AAG, and one in which nucleotides upstream from a second AUG codon are deleted. Thus we show that translation is not initiated at the UAG and conclude that synthesis of aldolase in the parasite starts at an AUG, provided after splicing of pre-mRNA. PMID- 1915281 TI - Transfer of rpl22 to the nucleus greatly preceded its loss from the chloroplast and involved the gain of an intron. AB - Most chloroplast and mitochondrial proteins are encoded by nuclear genes that once resided in the organellar genomes. Transfer of most of these genes appears to have occurred soon after the endosymbiotic origin of organelles, and so little is known about the process. Our efforts to understand how chloroplast genes are functionally transferred to the nuclear genome have led us to discover the most recent evolutionary gene transfer yet described. The gene rpl22, encoding chloroplast ribosomal protein CL22, is present in the chloroplast genome of all plants examined except legumes, while a functional copy of rpl22 is located in the nucleus of the legume pea. The nuclear rpl22 gene has acquired two additional domains relative to its chloroplast ancestor: an exon encoding a putative N terminal transit peptide, followed by an intron which separates this first exon from the evolutionarily conserved, chloroplast-derived portion of the gene. This gene structure suggests that the transferred region may have acquired its transit peptide by a form of exon shuffling. Surprisingly, phylogenetic analysis shows that rpl22 was transferred to the nucleus in a common ancestor of all flowering plants, at least 100 million years preceding its loss from the legume chloroplast lineage. PMID- 1915283 TI - Interaction of antibiotics with A- and P-site-specific bases in 16S ribosomal RNA. AB - We have studied the interactions of the antibiotics apramycin, kasugamycin, myomycin, neamine and pactamycin with 16S rRNA by chemical probing of drug ribosome complexes. Kasugamycin and pactamycin, which are believed to affect translational initiation, protect bases in common with P-site-bound tRNA. While kasugamycin protects A794 and G926, and causes enhanced reactivity of C795, pactamycin protects G693 and C795. All four of these bases were previously shown to be protected by P-site tRNA or by edeine, another P-site inhibitor. Apramycin and neamine, which both induce miscoding and inhibit translocation, protect A1408, G1419 and G1494, as was also found earlier for neomycin, gentamicin, kanamycin and paromomycin. A1408 and G1494 were previously shown to be protected by A-site tRNA. Surprisingly, myomycin fails to give strong protection of any bases in 16S rRNA, in spite of having an apparently identical target site and mode of action to streptomycin, which protects several bases in the 915 region. Instead, myomycin gives only weak protection of A1408. These results suggest that the binding site(s) of streptomycin and myomycin have yet to be identified. PMID- 1915284 TI - The 3 A crystal structure of yeast initiator tRNA: functional implications in initiator/elongator discrimination. AB - A significantly improved molecular model of yeast initiator tRNA (ytRNA(iMet) has been prepared that gives insight into the structural basis of eukaryotic initiator tRNA's unique function. This study was made possible by X-ray data collected at synchrotron radiation sources with the newly developed technologies of 'imaging plates' and 'storage phosphors'. These data extend beyond the resolution limit of 4.0 A reported previously to a current limit of 3.0 A and are considerably more accurate. Refinement of the model against the new data (R factor = 21.5%) clearly reveals a novel modification and a set of tertiary interactions involving sequence features characteristic of eukaryotic initiator tRNAs. We hypothesize these to be the structural elements responsible for part of the special function of yeast tRNA(iMET). PMID- 1915286 TI - The protein encoded by the rolB plant oncogene hydrolyses indole glucosides. AB - The rolB gene of Agrobacterium rhizogenes, whose expression stimulates the formation of roots by transformed plant tissues and other growth alterations in transgenic plants, codes for a beta-glucosidase able to hydrolyse indole-beta glucosides. Indeed, we show that extracts of bacteria and/or plant tissue expressing the rolB protein hydrolyse indoxyl-beta-glucoside (plant indican). Because of the structural similarity between indoxyl-beta-glucoside and indole-3 acetyl-beta-glucoside (IAA-beta-glucoside), we propose that the physiological and developmental alterations in transgenic plants expressing the rolB gene could be the result of an increased intracellular auxin activity caused by the release of active auxins from inactive beta-glucosides. Thus two of the oncogenes carried by the T-DNA of the plant pathogen Agrobacterium rhizogenes (rolB and rolC) perturb plant growth and development by coding for beta-glucosidases with distinct specificities. Whereas the rolC beta-glucosidase releases cytokinins from their glucoside conjugates, the rolB encoded protein hydrolyses indole-beta-glucosides. The combined action of these two genes therefore is expected to modulate the intracellular concentration of two of the main growth factors active in plants. PMID- 1915285 TI - A single base change in the acceptor stem of tRNA(3Leu) confers resistance upon Escherichia coli to the calmodulin inhibitor, 48/80. AB - We have isolated several classes of spontaneous mutants resistant to the calmodulin inhibitor 48/80 which inhibits cell division in Escherichia coli K12. Several mutants were also temperature sensitive for growth and this property was exploited to clone a DNA fragment from an E. coli gene library restoring growth at 42 degrees C and drug sensitivity at 30 degrees C in one such mutant. Physical and genetic mapping confirmed that both the mutation and the cloned DNA were located at 15.5 min on the E. coli chromosome at a locus designated feeB. By subcloning, complementation analysis and sequencing, the feeB locus was identified as identical to the tRNA(CUALEU) gene. When the mutant locus was isolated and sequenced, the mutation was confirmed as a single base change, C to A, at position 77 in the acceptor stem of this rare Leu tRNA. In other studies we obtained evidence that this mutant tRNA, recognizing the rare Leu codon, CUA, was defective in translation at both permissive and non-permissive temperatures. The feeB1 mutant is defective in division and shows a reduced growth rate at non permissive temperature. We discuss the possibility that the mutant tRNA(3Leu) is limiting for the synthesis of a polypeptide(s), requiring several CUA codons for translation which in turn regulates in some way the level or activity of the drug target, a putative cell cycle protein. PMID- 1915287 TI - The three-dimensional structure of reovirus obtained by cryo-electron microscopy. AB - The structures of reovirus serotypes T2J (Jones), T3D (Dearing) and the T3D core particle have been determined by cryo-electron microscopy and image processing. At a resolution of 30 A the two serotypes have similar features. The core is visible within the virus structure. The outer surface of the virus particles contains 120 holes at T = 13.1 local 6-fold axes. The holes penetrate into the virus as far as the surface of the internal core shell. Protrusions extending 4 nm from the virus surface surround each hole on the outside of the virus. At the 5-fold axes on the surface of the virus flat 'penton craters' form covers over the underlying core spikes. The detailed structure of the reovirus shell is very different to that of rotavirus although both have holes at T = 13.1 axes. Little evidence was seen of reovirus fibres extending from the virus surface. PMID- 1915288 TI - Towards a transgenic mouse model of sickle cell disease: hemoglobin SAD. AB - In order to obtain a transgenic mouse model of sickle cell disease, we have synthesized a novel human beta-globin gene, beta SAD, designed to increase the polymerization of the transgenic human hemoglobin S (Hb S) in vivo. beta SAD (beta S-Antilles-D Punjab) includes the beta 6Val substitution of the beta S chain, as well as two other mutations, Antilles (beta 23Ile) and D Punjab (beta 121Gln) each of which promotes the polymerization of Hb S in human. The beta SAD gene and the human alpha 2-globin gene, each linked to the beta-globin locus control region (LCR) were co-introduced into the mouse germ line. In one of the five transgenic lines obtained, SAD-1, red blood cells contained 19% human Hb SAD (alpha 2 human 1 beta 2SAD) and mouse-human hybrids in addition to mouse hemoglobin. Adult SAD-1 transgenic mice were not anemic but had some abnormal features of erythrocytes and slightly enlarged spleens. Their erythrocytes displayed sickling upon deoxygenation in vitro. SAD-1 neonates were anemic and many did not survive. In order to generate adult mice with a more severe sickle cell syndrome, crosses between the SAD progeny and homozygous for beta thalassemic mice were performed. Hemoglobin SAD was increased to 26% in beta thal/SAD-1 mice which exhibited: (i) abnormal erythrocytes with regard to shape and density; (ii) an enlarged spleen and a high reticulocyte count indicating an increased erythropoiesis; (iii) mortality upon hypoxia; (iv) polymerization of hemolysate similar to that obtained in human homozygous sickle cell disease; and (v) anemia and mortality during development. PMID- 1915289 TI - Aberrant melanogenesis and melanocytic tumour development in transgenic mice that carry a metallothionein/ret fusion gene. AB - We generated four independent transgenic mouse lines that showed severe melanosis of the whole body by introducing the ret oncogene fused to the mouse metallothionein (MT)-I promoter-enhancer (MT/ret). Whereas melanogenesis was accelerated without distinct proliferative disorders in one line, melanocytic tumours frequently developed in the other three lines. Northern hybridization and in situ hybridization analyses showed that tumour cells and non-tumorous melanin producing cells expressed the transgene at high levels. The aberrant melanogenesis and tumour development were influenced by genetic and environmental factors. Furthermore, crossbreeding experiments between the transgenic mice and Wv mice suggested that the ret gene product can partially compensate for the defect of melanocyte development in Wv mice. This is a novel mammalian model in which melanosis and melanocytic tumours develop stepwise, triggered by a single transgene. PMID- 1915290 TI - Heterogeneity of microsomal Ca2+ stores in chicken Purkinje neurons. AB - Chicken cerebellum microsomes were subfractionated on isopycnic, linear sucrose (15-50%) density gradients. The distribution of four markers of intracellular, rapidly-exchanging Ca2+ stores, i.e. the Ca2+ pump, the receptors for inositol 1,4,5-trisphosphate (IP3) and ryanodine (Ry), and calsequestrin (CS, an intralumenal, high capacity Ca2+ binding protein) was investigated biochemically and immunologically. In the cerebellum, high levels of these markers are expressed by one of the cell types, the Purkinje neuron. Heavy subfractions were enriched in both CS and Ry receptor, intermediate subfractions in the IP3 receptor, while the Ca2+ pump was present in both intermediate and heavy subfractions. Intact cells and pelleted subfractions were examined by conventional and immuno-electron microscopy (immunogold labeling of ultrathin cryosections with anti-CS and anti-IP3 receptor antibodies). Of the strongly CS labeled, moderately dense-cored vacuoles (calciosomes) recently described in chicken Purkinje neurons only partly exhibited labeling for the IP3 receptor as well, and the rest appeared negative. The latter were enriched in a heavy subfraction of the gradient where Ry receptors were also concentrated, whereas the CS-rich vacuoles in an intermediate subfraction were almost always IP3 receptor-positive. The population of CS-rich calciosomes of chicken Purkinje neurons appears therefore to be molecularly heterogeneous, with a part responsive to IP3 and the rest possibly sensitive to Ry. PMID- 1915292 TI - The receptor-like protein tyrosine phosphatase HPTP alpha has two active catalytic domains with distinct substrate specificities. AB - Cloning and expression of the homologous domains of the receptor-like tyrosine phosphatase HPTP alpha shows that both domain 1 (D1) and domain 2 (D2) are enzymatically active. The two domains display different substrate specificities with D1 preferentially dephosphorylating MBP approximately RR-src greater than PNPP while D2 favours PNPP much much greater than RR-src and is inactive towards MBP. Each domain has lower activity than an expressed protein containing both domains. Analysis of chimaeric D1/2 proteins suggests that no particular region of D2 is responsible for the low activity of D2 on RR-src and that the specificity differences of D1 and D2 reflect overall sequence dissimilarities. Activities of D1 and D2 are inhibited by zinc, vanadate and EDTA and differentially susceptible to inhibition by heparin and poly(Glu4:Tyr1). Unusually, the activity of the protein containing both domains is stimulated by these polyanions. Regions amino-terminal to each domain are important for catalysis since deletion of these sequences abolishes phosphatase activity. Activity of the double domain polypeptide was also lost upon deletion of the sequence amino-terminal to D1, indicating that inactivation of D1 may suppress D2 activity. Differences in substrate specificity and responses to effectors and the interdependence between the two domains are likely important properties in the function of this PTPase in signal transduction. PMID- 1915291 TI - The integrity of the conserved 'WS motif' common to IL-2 and other cytokine receptors is essential for ligand binding and signal transduction. AB - Recent studies have identified a new family of cytokine receptors, which is primarily characterized by the conservation of periodically interspersed four cysteine residues and the W-S-X-W-S sequence ('WS motif') within the extracellular domain. However, the role of such conserved structures still remains elusive, in particular that of the WS motif. Interleukin-2 (IL-2) is known to play a critical role in the clonal expansion of antigen-stimulated T lymphocytes, and the IL-2 signal is delivered by one of the receptor components, the IL-2 receptor beta (IL-2R beta) chain. The IL-2R beta chain, unlike the IL-2R alpha chain, belongs to this receptor family. In the present study, we analyzed the function of the WS motif of IL-2R beta (Trp194-Ser195-Pro196-Trp197-Ser198) with the use of site-directed mutagenesis. Our results indicate the critical role of the two Trp residues in the proper folding of the IL-2R beta extracellular domain and point to the general functional importance of the WS motif in the new cytokine receptor family. PMID- 1915293 TI - Energetically distinct early and late stages of HlyB/HlyD-dependent secretion across both Escherichia coli membranes. AB - The alternative secretion pathway which exports hemolysin across both Escherichia coli membranes into the surrounding medium is directed by an uncleaved C-terminal targeting signal and the membrane translocator proteins HlyD and HlyB. In order to identify stages and intermediates in this unconventional secretion process we have examined the effect of inhibition of the total proton motive force (delta P) and its components during the in vivo HlyB/HlyD-dependent export of a 22.4 kDa secretion competent HlyA C-terminal peptide (Actp). Secretion of Actp was severely inhibited by the proton ionophore carbonylcyanide m chlorophenylhydrazone (CCCP), which collapses simultaneously membrane potential delta psi and the proton gradient delta pH, and also by valinomycin/K+, a potassium ionophore which disrupts delta psi. The inhibition of secretion by valinomycin/K+ was ameliorated by imposition of a pH gradient, the second component of the delta P, and selective depletion of delta pH by nigericin also blocked secretion. This indicates that, as in the secretion of beta-lactamase to the periplasm, HlyB/D-directed secretion requires delta P itself and not specifically one of its components. However, inhibition of HlyB/D-dependent secretion was only marked when CCCP, valinomycin/K+ or nigericin were present during the early stage of Actp secretion; at a later stage the secretion was not significantly inhibited. HlyB/D-dependent secretion appears therefore to share with conventional secretion across the cytoplasmic membrane an early requirement for delta P, but comprises in addition a late stage which does not require delta P, delta psi or delta pH. The translocation intermediate identified in the delta P-independent late stage of secretion was associated with the membrane fraction. Analysis of the protease accessibility of this intermediate in whole cells and spheroplasts showed that it was not in the periplasm, nor was it exposed on the cell surface or on the periplasmic faces of either the inner or outer membranes. This may reflect its close association with the inner membrane or a membrane translocation complex. PMID- 1915294 TI - Sequential action of mitochondrial chaperones in protein import into the matrix. AB - Translocation and folding of proteins imported into mitochondria are mediated by two matrix-localized chaperones, mhsp70 and hsp60. In order to investigate whether these chaperones act sequentially or in parallel, we studied their interaction with newly imported precursor proteins in isolated yeast mitochondria by coimmunoprecipitation. All precursors bound transiently to mhsp70. Release from mhsp70 required hydrolysis of ATP and did not immediately generate a tightly folded protein. For example, after imported mouse dihydrofolate reductase (a soluble monomeric enzyme) had been released from mhsp70, folding to a protease resistant conformation occurred only after a lag and was much slower than the release. Under standard import conditions, no significant association of DHFR with hsp60 could be detected. Similarly, newly imported hsp60 subunit was released from mhsp70 as an incompletely folded, unassembled intermediate which accumulated at low temperature and assembled to hsp60 14-mer at higher temperature in an ATP-dependent manner. Mas2p (the larger subunit of the MAS encoded processing protease) first bound to mhsp70, then to hsp60, and only then assembled with its partner subunit, Mas1p. We propose that ATP-dependent release from mhsp70 is insufficient to cause folding of imported proteins and that assembly of hsp60 and Mas2p requires sequential, ATP-dependent interactions with mhsp70 and hsp60. PMID- 1915295 TI - Plastid translation and transcription genes in a non-photosynthetic plant: intact, missing and pseudo genes. AB - The non-photosynthetic, parasitic flowering plant Epifagus virginiana has recently been shown to contain a grossly reduced plastid genome that has lost many photosynthetic and chloro-respiratory genes. We have cloned and sequenced a 3.9 kb domain of plastid DNA from Epifagus to investigate the patterns of evolutionary change in such a reduced genome and to determine which genes are still present and likely to be functional. This 3.9 kb domain is colinear with a 35.4 kb region of tobacco chloroplast DNA, differing from it by a minimum of 11 large deletions varying in length from 354 bp to 11.5 kb, as well as by a number of small deletions and insertions. The nine genes retained in Epifagus encode seven tRNAs and two ribosomal proteins and are coextensive and highly conserved in sequence with homologs in photosynthetic plants. This suggests that these genes are functional in Epifagus and, together with evidence that the Epifagus plastid genome is transcribed, implies that plastid gene products play a role in processes other than photosynthesis and gene expression. Genes that are completely absent include not only photosynthetic genes, but surprisingly, genes encoding three subunits of RNA polymerase, four tRNAs and one ribosomal protein. In addition, only pseudogenes are found for two other tRNAs. Despite these defunct tRNA genes, codon and amino acid usage in Epifagus protein genes is normal. We therefore hypothesize that the expression of plastid genes in Epifagus relies on the import of nuclear encoded tRNAs and RNA polymerase from the cytoplasm. PMID- 1915296 TI - A 210 kDa nuclear matrix protein is a functional part of the mitotic spindle; a microinjection study using SPN monoclonal antibodies. AB - Six monoclonal antibodies identify a 210 kDa polypeptide which shows a cell cycle specific redistribution from the nucleus to the mitotic spindle. In interphase cells this polypeptide was localized in the nucleus and behaved during differential cell extraction as a component of the nuclear matrix. It accumulated in the centrosome region at prophase, in the pole regions of the mitotic spindle at metaphase and in crescents at the poles in anaphase, and reassociated with the nuclei as they reformed in telophase. Due to its staining pattern we call the protein the Spindle Pole-Nucleus (SPN) antigen. The localization of SPN antigen during mitosis was dependent on the integrity of the spindle since treatment of cells with nocodazole resulted in the dispersal of SPN antigen into many small foci which acted as microtubule organizing centres when the drug was removed. The SPN antigen was present in nuclei and mitotic spindles of all human and mammalian cell lines and tissues so far tested. When microinjected into the cytoplasm or nuclei of HeLa cells, one antibody caused a block in mitosis. Total cell number remained constant or decreased slightly after 24 h. At this time, about half the cells were arrested in a prometaphase-like state and revealed aberrant spindles. Many other cells were multinucleate. These results show that the SPN antigen is a protein associated with mitotic spindle microtubules which has to function correctly for the cell to complete mitosis. PMID- 1915297 TI - A factor that positively regulates cell division by activating transcription of the major cluster of essential cell division genes of Escherichia coli. AB - Cell division in Escherichia coli requires the products of the ftsQ, ftsA and ftsZ genes. It is not known how the cell regulates the cellular concentrations of these essential elements of the division system. We describe here a factor that activates cell division by specifically increasing transcription from one of the two promoters that lie immediately upstream of the ftsQAZ gene cluster. The trans acting factor is the product of the sdiA gene, which was isolated on the basis of its ability to suppress the division inhibitory effect of the MinC/MinD division inhibitor. In addition, the sdiA gene product suppressed the action of other chromosomally encoded division inhibitors, induced minicell formation in wild type cells, and restored division activity to an ftsZ temperature-sensitive mutant grown under nonpermissive conditions. All of these properties were explained by the ability of the sdiA gene product specifically to increase transcription of the ftsQAZ gene cluster, resulting in an increase in cellular concentration of the FtsZ protein. The sdiA gene product is the first factor thus far identified that specifically regulates expression of this key group of cell division genes. PMID- 1915298 TI - Control of yeast GAL genes by MIG1 repressor: a transcriptional cascade in the glucose response. AB - Glucose repression is a global regulatory mechanism in yeast. We have investigated how glucose regulates the GAL genes, which are required for galactose fermentation. We found that the GAL genes are controlled by a transcriptional cascade. Thus, GAL4, which encodes an activator of the GAL genes, is repressed by MIG1, a zinc finger protein that binds to the GAL4 promoter. MIG1 has a dual role in control of the GAL genes, since MIG1 also binds to the promoter of GAL1, a gene regulated by GAL4. A disruption of MIG1 interacts synergistically with a disruption of GAL80, a gene involved in galactose induction. This suggests that the MIG1-dependent response to glucose is amplified by down-regulation of the induction pathway. PMID- 1915300 TI - A novel lineage-specific nuclear factor regulates mb-1 gene transcription at the early stages of B cell differentiation. AB - The mb-1 gene, which encodes a protein associated with membrane-bound antibody, is expressed only at the early stages of B cell differentiation. To gain insight into the mechanisms that underlie temporally regulated gene expression, we examined the mb-1 promoter region for interactions with cell type-specific DNA binding proteins. Here, we report the characterization of a novel nuclear factor that recognizes the mb-1 promoter. This DNA binding activity, termed Early B cell Factor, or EBF, is expressed in early stage B cells, but not in late stage B cells, T cells or non-lymphoid cells. EBF recognizes the nucleotide sequence 5' CAAGGGAAT-3' in the mb-1 and major histocompatibility complex (MHC) class II A alpha d promoters. The binding of EBF to DNA was characterized by DNase I footprinting and by methylation interference analysis which indicated both major and minor groove contacts. The specificity of EBF binding is distinct from that of other nuclear factors expressed in hematopoietic cells. EBF appears to consist of at least two polypeptides of approximately 70-75 kDa and 80-85 kDa. The EBF binding site was important for maximal mb-1 promoter activity in early stage B cells. Moreover, the EBF binding site conferred correct lineage- and stage specific transcriptional activity upon a heterologous promoter in a context dependent manner. Thus, EBF appears to represent an important transcriptional regulator of B cell specific gene expression. PMID- 1915299 TI - RNA polymerase I can mediate expression of CAT and neo protein-coding genes in Trypanosoma brucei. AB - We show that the ribosomal RNA (rRNA) promoter can efficiently direct expression of protein-coding genes in the parasitic protozoan Trypanosoma brucei. The rRNA promoter was characterized by: (i) point mutations at the rRNA transcription initiation site which completely abolished its promoter function in transient CAT transformation assays; (ii) the alpha-amanitin resistance of transcription of rRNA promoter-neomycin phosphotransferase (neo) genes in stably transformed trypanosomes; and (iii) the nucleolar location of neo RNA, synthesized under the control of the rRNA promoter. The rRNA promoter-derived CAT mRNA required a 3' splice acceptor site and the neo mRNA was trans-spliced and polyadenylated. In situ hybridization revealed neo RNA at the nucleolus in stably transformed trypanosomes in which rRNA promoter-neo constructs were integrated either at a rRNA locus or at a locus for the procyclic acidic repetitive protein (PARP) coding genes. We postulate that trans-splicing, by uncoupling the requirement for transcription of protein-coding genes by RNA polymerase II, allows RNA polymerase I mediated protein-coding gene transcription, presumably because a 5' cap can be transferred to the pre-mRNA by trans-splicing. PMID- 1915301 TI - Transcription from the adenovirus major late promoter uses redundant activating elements. AB - The adenovirus major late promoter (MLP) has been analyzed by constructing recombinant viral genomes containing mutations in possible promoter elements. Single base pair changes in the TATA box had no effect on viral replication, and MLP expression, as measured by the accumulation of late mRNAs, was at wild type levels. However, a double mutation in the TATA box reduced viral replication and MLP expression, demonstrating that the TATA box is important, although not essential, for maximal activity in virus. Primer extension analysis showed that the mRNAs were initiated at the correct position. A mutation in the CAAT box was viable, and had only minor effects on MLP expression. However, this mutation when coupled to a single mutation in the TATA box, severely reduced viral replication and expression from the MLP. Similarly, a viable mutation in the UPE, shown previously to abolish binding of USF, coupled to a single mutation in the TATA box was lethal. These results suggest that both USF and the CAAT box binding factor CP1 can interact with TFIID to effect activation, and thus that the mechanism of activation is functionally redundant. PMID- 1915302 TI - DNA template effect on RNA splicing: two copies of the same gene in the same nucleus are processed differently. AB - Many cellular and viral genes are parts of complex transcription units containing multiple splicing choices. During the course of an adenoviral replicative cycle, different spliced versions of a single gene predominate, depending on the stage of infection. This is true for several adenoviral genes. In this paper we show for the viral E1B transcription unit that splice site usage regulates this process. The change in alternative splicing in this system does not depend on the sequence of the transcribed genes. Non-adenoviral genes, such as the SV40 early region and the polyoma early region, which normally show little or no regulation of spliced RNA product formation, become regulated for mRNA production after insertion into the adenoviral genome. Additional studies show that E1B splicing regulation in adenovirus is a cis effect. Staggered infections using two discernable viral genomes resulted in a situation where both early and late genomes exist in the same nucleus. Neither genome was able to impose its regulated splicing pattern on the other, indicating that the cue for the switch in viral gene splicing is not directly dependent on global changes in trans acting splicing factors. This suggests a model where the signal for changes in RNA processing for the E1B gene is linked to the state of the DNA template or its localization within nuclear subcompartments. PMID- 1915303 TI - Trans splicing integrates an exon of 22 nucleotides into the nad5 mRNA in higher plant mitochondria. AB - The genes coding for NADH dehydrogenase subunit 5 (nad5) in mitochondria of the higher plants Oenothera and Arabidopsis are split into five exons that are located in three distant genomic regions. These encode exons a + b, c and d + e, respectively. Maturation of the mRNAs requires two trans splicing events to integrate exon c of only 22 nucleotides. Both trans splicing reactions involve mitochondrial group II intron sequences that allow base pairings in the interrupted domain IV, demonstrating the flexibility of intron structures. The observation of fragmented intron sequences in plant mitochondria suggests that trans splicing is more widespread than previously assumed. RNA editing by C to U alterations in both Oenothera and Arabidopsis open reading frames improves the evolutionary conservation of the encoded polypeptides. Three C to U RNA editing events were observed in intron sequences. PMID- 1915304 TI - Chloroplast ribosomal intron of Chlamydomonas reinhardtii: in vitro self splicing, DNA endonuclease activity and in vivo mobility. AB - All chloroplast 23S ribosomal RNA genes of the unicellular alga Chlamydomonas reinhardtii contain an 888 bp group I intron with an internal open reading frame (ORF). A precursor RNA encompassing the intron with its 5' and 3' flanking sequences was shown to self-splice both during in vitro transcription and upon incubation of the isolated pre-RNA under self-splicing conditions. Expression of the internal ORF in Escherichia coli in the presence of a plasmid containing a cDNA corresponding to the intronless form of the 23S rRNA gene resulted in specific cleavage of the cDNA at or close to the exon junction sequence. To test whether this ORF-encoded double-strand DNA endonuclease is involved in intron mobility in vivo, the same ribosomal cDNA was stably integrated into the C. reinhardtii chloroplast genome using particle gun mediated transformation. All the transformants with the cDNA integrated at the expected site in the chloroplast genome had the intron precisely inserted at the artificial exon junction site. These experiments demonstrate that the chloroplast ribosomal intron of C. reinhardtii behaves as a ribozyme in vitro and also as a mobile genetic element in vivo provided a target site is present. PMID- 1915308 TI - Retraction. Infectious measles virus from cloned cDNA. PMID- 1915306 TI - Substrate specificity of the dsRNA unwinding/modifying activity. AB - Double-stranded RNA (dsRNA) unwinding/modifying activity, which is present in a wide range of eukaryotic cells, has been previously shown to convert up to 50% of adenosine residues to inosines within intermolecular dsRNA. In the present study, we report that this activity also modifies, though slightly less efficiently, intramolecular double-stranded regions of synthetic RNAs. Our results widen the range of the possible biological substrates for the activity since many stem and loop type RNA secondary structures (intramolecular dsRNA), present in eukaryotic as well as viral transcripts, can potentially serve as substrates. In addition, we have found that the dsRNA unwinding/modifying activity requires a double stranded region of at least 15-20 base pairs (bp) for substrate recognition. Furthermore, modification efficiency was found to be critically dependent on the length of the double-stranded region; as the size decreased below 100 bp, it dropped precipitously. Our results suggest that efficient modification may occur only with relatively long (greater than 100 bp) dsRNA, perhaps because multiple copies of the enzyme must be bound. PMID- 1915305 TI - Homologous mRNA 3' end formation in fission and budding yeast. AB - Sequences resembling polyadenylation signals of higher eukaryotes are present downstream of the Schizosaccharomyces pombe ura4+ and cdc10+ coding regions and function in HeLa cells. However, these and other mammalian polyadenylation signals are inactive in S. pombe. Instead, we find that polyadenylation signals of the CYC1 gene of budding yeast Saccharomyces cerevisiae function accurately and efficiently in fission yeast. Furthermore, a 38 bp deletion which renders this RNA processing signal non-functional in S. cerevisiae has the equivalent effect in S. pombe. We demonstrate that synthetic pre-mRNAs encoding polyadenylation sites of S. pombe genes are accurately cleaved and polyadenylated in whole cell extracts of S. cerevisiae. Finally, as is the case in S. cerevisiae, DNA sequences encoding regions proximal to the S. pombe mRNA 3' ends are found to be extremely AT rich; however, no general sequence motif can be found. We conclude that although fission yeast has many genetic features in common with higher eukaryotes, mRNA 3' end formation is significantly different and appears to be formed by an RNA processing mechanism homologous to that of budding yeast. Since fission and budding yeast are evolutionarily divergent, this lower eukaryotic mechanism of mRNA 3' end formation may be generally conserved. PMID- 1915307 TI - Sequence-independent RNA cleavages generate the primers for plus strand DNA synthesis in hepatitis B viruses: implications for other reverse transcribing elements. AB - Reverse transcription of RNA into duplex DNA requires accurate initiation of both minus and plus strand DNA synthesis; this in turn requires the generation of specific primer molecules. We have examined plus strand primer generation in the hepatitis B viruses, small DNA viruses that replicate via reverse transcription. The plus strand primer in these viruses is a short capped RNA derived from the 5' end of the RNA template by cleavage at a specific set of sites. To elucidate the cleavage mechanism we constructed a series of viral mutants bearing alterations in and around the cleavage sites. Our results reveal that the cleavage reaction is sequence-independent and indicate that the cleavage sites are positioned by measurement of the distance from the 5' end of the RNA. Comparison of these findings with what is known about RNase H-mediated primer generation in retroviruses and other retroid elements suggests that, despite many divergent features, some common molecular features are preserved. PMID- 1915309 TI - Mutagenicity of methylazoxymethanol acetate in the presence of alcohol dehydrogenase, aldehyde dehydrogenase, and rat liver microsomes in Salmonella typhimurium His G46. AB - Methylazoxymethanol (MAM) is the short-lived toxic and carcinogenic aglycone of cycasin, a natural component of the cycad plant. In the present study, the stable acetate ester of MAM, MAM acetate, was tested in combination with porcine liver esterase and Salmonella typhimurium His G46 to study the comparative mutagenicity of this compound in the presence of rat hepatic alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and rat liver microsomes. In the presence of rat liver microsomes and an NADPH-generating system, mutagenicity of MAM acetate was not significantly altered. However, addition of rat liver 105,000g supernatant fraction and/or NAD+ significantly increased the number of his+ revertants above control. A concentration-dependent increase in mutagenicity of MAM acetate was observed for NAD+ from 50 to 200 microM, while NADP+ caused a decrease in mutagenicity of MAM acetate in this same concentration range. Pyrazole (100-500 microM) had no significant effect on mutagenicity of MAM acetate in the presence of rat liver 105,000g supernatant, while disulfiram at 500 microM resulted in a significant decrease in mutagenicity of MAM acetate. The results of this study implicate ALDH as essential in activation of MAM acetate to a mutagenic species in this system, while the role of ADH and microsomes appears to be minimal. PMID- 1915310 TI - DNA sequence analysis of X-ray induced Adh null mutations in Drosophila melanogaster. AB - The mutational spectrum for 28 X-ray induced mutations and 2 spontaneous mutations, previously determined by genetic and cytogenetic methods, consisted of 20 multilocus deficiencies (19 induced and 1 spontaneous) and 10 intragenic mutations (9 induced and 1 spontaneous). One of the X-ray induced intragenic mutations was lost, and another was determined to be a recombinant with the allele used in the recovery scheme. The DNA sequence of two X-ray induced intragenic mutations has been published. This paper reports the results of DNA sequence analysis of the remaining intragenic mutations and a summary of the X ray induced mutational spectrum. Only one of the X-ray induced mutations is a single base change, a C to G transversion (AdhnLA80). Therefore, the mutational spectrum of X-ray induced mutations consists predominantly of deletions that are observed to range in size from two base pairs to deletions of a large number of loci as determined by genetic complementation analysis. The combination of DNA sequence analysis with genetic complementation analysis shows a continuous distribution in size of deletions rather than two different types of mutations consisting of deletions and "point mutations." Sequencing is shown to be essential for detecting intragenic deletions. Of particular importance for future studies is the observation that all of the intragenic deletions consist of a direct repeat adjacent to the break-point with one of the repeats deleted. PMID- 1915311 TI - Enumeration of 6-thioguanine-resistant T-lymphocytes in the peripheral blood of nonhuman primates (cynomolgus monkeys). AB - We have investigated the use of cynomolgus monkeys (Macaca fascicularis) as a model of somatic cell mutagenesis in non-human primates. Using techniques described by Albertini (Mutation Research 150:411-422, 1985) for similar studies in humans, the frequency of TG-resistant T-lymphocytes in the peripheral blood was determined in animals that were either untreated or treated with ethylnitrosourea. The frequency of TG-resistant cells in untreated males was (mean +/- SD) 6.0 +/- 5.9 per 10(6) cells and for untreated females was 2.9 +/- 2.7 per 10(6) cells. The spontaneous frequency of TG-resistant cells for all animals was 4.2 +/- 4.44 per 10(6) cells. Maximum frequency of TG-resistant cells for two animals treated with a single I.P. dose of ENU was 45.1 and 77.9 per 10(6) cells. Substantial increases in frequencies of TG-resistant cells were not seen until at least 63 days after treatment. The TG-resistant phenotype of clones isolated in the assay was stable after growth for 2 weeks in the absence of selective agent. Many of the TG-resistant clones selected were frozen for future molecular analysis. PMID- 1915312 TI - Induction of micronuclei in mouse bone marrow cells: an evaluation of nucleoside analogues used in the treatment of AIDS. AB - Various nucleoside analogues are being used or are being considered for use as therapeutic drugs to inhibit replication of the HTLV-III/LAV virus in infected human cells. Here, the ability of seven nucleoside analogues, a combination of two analogues, and two other therapeutic compounds to induce genotoxic and cytotoxic damage in vivo was evaluated in the mouse bone marrow micronucleus test. Using a 3-consecutive-day oral treatment protocol, almost all of the test chemicals induced a significant increase in the frequency of micronucleated polychromatic erythrocytes (MN-PCE) in male B6C3F1 mice, ranked in decreasing potency as 6-thioguanine greater than Cytarabine HCl greater than 3'-azido-3' deoxythymidine (AZT)/2',3'-dideoxycytidine combination = AZT greater than Ribavirin = 2',3'-didehydro-3'-deoxythymidine greater than 2',3'-dideoxyadenosine = 2',3'-dideoxycytidine. The frequency of MN-PCE was not increased significantly by treatment with 2',3-dideoxyinosine (DDI) or pentamidine isethionate (PI). The differential ability of AZT and DDI to induce MN in mouse bone marrow was verified from peripheral blood smears prepared from subchronic (90 day) oral studies. The lack of genotoxic activity by DDI was route-specific since, when tested by intraperitoneal injection, a small but significant increase in MN-PCE was observed. A number of these chemicals induced a significant depression in erythropoiesis. However, there was not a significant correlation between the increase in MN-PCE and the depression in the percentage of PCE. This lack of a correlation suggests that factors other than DNA damage may contribute to the inhibition in the rate of erythropoiesis. The presence of increased levels of micronuclei in bone marrow PCE following treatment with various nucleoside analogues suggests that intrinsic genotoxic activity in mammalian cells should be one factor considered during drug selection for AIDS therapy. PMID- 1915313 TI - Lack of genotoxicity of cross-linked acrylate polymers in four short-term genotoxicity assays. AB - Three cross-linked polyacrylate polymers containing either methylenebis acrylamide (MBA), trimethylolpropane triacrylate (TMPTA), or triallylamine (TAA) cross-linkers were tested for genotoxicity with the Salmonella mammalian microsome assay, the L5178Y mouse lymphoma TK +/- assay, the unscheduled DNA synthesis assay in primary cultures of rat hepatocytes, and the in vivo bone marrow cytogenetic assay. The results indicate that none of the three polymers was genotoxic in these assays. PMID- 1915314 TI - Relationship between DNA adduct formation and unscheduled DNA synthesis (UDS) in cultured mouse epidermal keratinocytes. AB - Primary cultures of mouse epidermal keratinocytes from SENCAR mice were treated with 7,12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene [B(a)P], (+/-)7 beta-8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+/ )anti-BPDE], and (+/-)7 beta, 8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10 tetrahydrobenzo(a)pyrene [(+/-)syn-BPDE] to examine the relationship between DNA adduct formation and the induction of unscheduled DNA synthesis (UDS). DNA adducts were measured as pmol hydrocarbon bound per mg of DNA, and UDS was quantitated autoradiographically as net grains per nucleus. A good correlation was observed between the levels of UDS detected and the amount of DNA adducts present in the cell population when comparing similar compounds within the linear dose-response range of 0.005 micrograms/ml-0.25 micrograms/ml. A higher rate of UDS for a given level of DNA adducts was interpreted as an increased efficiency of DNA repair. In some cases, an increase in the efficiency of DNA excision repair correlated with lower tumor-initiating activity. For this family of PAH, the concentration below which UDS could no longer be detected was approximately 0.01 microgram/ml. However, DNA adducts were measurable at concentrations of 0.01 and 0.005 micrograms/ml. The limits of detection of the current UDS assay in the SENCAR MEK culture system occurred at hydrocarbon adduct levels of approximately 10 pmol/mg DNA, or approximately 1 adduct per 3 x 10(5) bases. Additionally, the UDS assay was unable to detect DNA repair induced by the weakly carcinogenic PAHs, dibenz(aj)anthracene and 7-methyl-dibenz(aj)anthracene. The UDS assay did detect DNA repair by the more strongly carcinogenic PAH, 6-methylcholanthrene. These results suggest that the present UDS assay with MEKs is a useful assay for the rapid screening of potential genotoxic agents. However, the limits of sensitivity are such that the current assay may be unable to detect a low level of DNA damage induced by some weakly genotoxic (carcinogenic) agents. In addition, while the limits of sensitivity determined in these experiments apply to the polycyclic aromatic hydrocarbon class, other classes of genotoxic compounds such as alkylating agents or crosslinking agents may exhibit different thresholds of detection. PMID- 1915315 TI - Antimutagenic activities of naturally occurring polyamines in Chinese hamster ovary cells in vitro. AB - Spermine and spermidine, ubiquitous polyamines present in bacteria and animal cells, are also involved in cell growth. Since they interact with the double helix, they can stabilize the DNA molecule. Recent evidence of the antimutagenic and anticarcinogenic capacity of spermine has focused attention on the mechanism(s) by which such agents can protect cells from induced damages. In the present paper we show the ability of spermine and spermidine to decrease the level of sister chromatid exchanges induced in Chinese hamster ovary cells cultivated in vitro, by treating them with Psoralen + UVA irradiation (able to induce mainly monoadducts and DNA cross-links). Two different mechanisms of polyamine action can be invoked to explain the preservative activity of this class of agents. PMID- 1915317 TI - Malaria in pregnancy: clinical features and outcome of treatment. AB - Over two consecutive malaria seasons in 1987 and 1988, 37 patients were admitted to the Gonder College Hospital with malaria in pregnancy. In 10 patients the diagnosis was missed initially and delayed for up to 72 hours after admission. The differential diagnoses considered on first line included incomplete abortion, labour, postpartum haemorrhage, and fulminant hepatitis in pregnancy. Twelve patients (32.4%) died, five of these died undelivered. Fifteen pregnancies (40.5%) ended up in abortion, preterm delivery with early neonatal death and still birth. This study has shown that malaria in pregnancy can have different clinical manifestations that may mislead the physician. This may delay the diagnosis and initiation of treatment which may have a fatal outcome for both the mother and the baby. PMID- 1915316 TI - Genotoxic effects of gossypol acetic acid on cultured murine erythroleukemia cells. AB - Gossypol acetic acid, a male anti-fertility drug, was evaluated for its effects on cell multiplication, chromosomes, scheduled and unscheduled DNA synthesis, and the surface ultrastructure in cultured murine erythroleukemia cells (clone 6A11A). Gossypol treatments inhibited cell multiplication at 10 and 20 micrograms/ml concentrations and this inhibitory effect increased with elevated dosage and prolonged treatment. Gossypol significantly depressed the mitotic index but did not alter chromosome numbers or increase the frequency of chromosomal structural abnormalities. Cell fraction techniques revealed that gossypol induced a negative effect on cellular DNA synthesis at concentrations as low as 3.3 micrograms/ml after 24 hr of treatment. The number of cells undergoing DNA synthesis decreased with increasing dosages and durations of drug exposure. An unscheduled DNA synthesis assay (UDS) found gossypol to be an active UDS inducing agent at certain dose levels and treatment times, as measured by increase in net nuclear gain and percentage of UDS cells (ANOVA, Bonferroni test, P less than 0.05). A scanning electron microscope study revealed that 10 micrograms/ml treatment with gossypol caused changes in mouse erythroleukemia cell surface ultrastructure characterized by general balding and the appearance of holes, often after 48 hr of treatment. PMID- 1915318 TI - Organophosphate pesticide poisoning in 50 Ethiopian patients. AB - Organophosphate pesticide poisoning in 50 patients treated at the Tikur Anbessa Hospital over a period of 6 years is described. Most of the cases were attempted suicide (94%). The majority of the patients presented with the typical clinical features of Parasympathetic overactivity. Atropine was the mainstay of treatment. Mortality from organophosphate pesticide poisoning was 20%. There is a strong need to device a national system of control of pesticides and educate the public about the dangers of pesticides. PMID- 1915319 TI - Levels of doses to radiological workers in Ethiopia: 1977-1988. AB - During the period 1977 to 1988, a total of 10,494 Eastman Kodak Type 2 film badges and 19,236 Vinten lithium fluoride thermoluminescence dosimeters (TLDS) were delivered to medical workers in Ethiopia of which 5,135 (48.93%) film badges and 19,177 (99.69%) TLDS were evaluated. The annual average occupational doses to the workers were estimated to be 1.44 and 4.51 mSv with corresponding collective dose equivalents of 0.29 and 4.51 man-Sv respectively. Comparisons of doses to similar workers in different countries were compiled from the literature. Based on the TLD results and the 1977 International Commission on Radiological Protection (ICRP) risk coefficients it is estimated that the occurrence of extra fatal and non-fatal cancer cases is in the order of 74 per million radiological workers per year. The hereditary defects expected are 18 and 36 cases in the next two and in all future generations respectively. During these periods, the number of institutions monitored rose from 35 to 88 while the workers monitored increased from 100 to 450. PMID- 1915320 TI - Risk behaviors for HIV infection: their occurrence and determinants in Jima-Town, southwestern Ethiopia. AB - Little is known about the occurrence of high risk behaviours for HIV infection among the general population of Ethiopia. With this in mind, 495 randomly selected males between 15 and 49 years of age were questioned about specific risk behaviours. From this interview a total and sex risk behaviour score were calculated and then analysed for their association with sociodemographic factors and knowledge and attitudes about AIDS. This investigation was carried out in the fall of of 1988 in Jima-Town, southwestern Ethiopia. Several high risk behaviours were found to be highly prevalent; 47.2% reported a history of sex with prostitutes (18% in the past month), and 39% reported receiving injections in the past year. Higher risk scores were significantly associated with high knowledge about AIDS and among skilled labourers and those between 25 to 34 years of age. PMID- 1915323 TI - A study and analysis of spinal canal diseases in the Black Lion Hospital by myelography. AB - Sixty seven lumbar and thoracic myelographic examinations were performed during the period February 1987 to September 1988. Fourteen patients (21%) had normal myelography while 53 (79%) patients had pathological findings. Spinal canal tumours accounted for the majority of complete CSF blocks (76.7%) Seventy-five per cent of the intradural tumours showed no abnormality on plain films of the vertebral column, whereas 75% of the extradural tumours had pathological findings. Dorsal (central) disc herniation was more frequent (70%) than lateral herniation with almost equal distribution at L5-S1 and L4-L5 disc spaces. Central disc herniation was more common at L4-L5 (71%). The measurement of the interpedicular distance on plain radiograph was not found to be diagnostic in our single case of spinal stenosis. PMID- 1915321 TI - Case report: haemorrhagic mesenteric cyst mimicking appendicitis. AB - A five-year old girl who presented with an acute abdominal emergency was found to have a haemorrhagic mesenteric cyst intraoperatively. The clinical picture and the mode of management are presented and discussed. The possibility of a complicated mesenteric cyst should be considered in the differential diagnosis in patients with an acute abdomen. PMID- 1915322 TI - Leech--an unusual cause of (laryngo-tracheal) obstruction. AB - A case of acute laryngo-tracheal obstruction in a 12-year old boy is presented. A live leech was removed from the larynx under general anaesthesia. A high index of suspicion of leeches as foreign bodies in children with acute onset of respiratory distress associated with hemoptysis and early surgical intervention is emphasized. PMID- 1915325 TI - Energy cost of front-crawl swimming in women. AB - The purpose of this study was to examine the relationship between the energy cost of swimming per unit distance (Cs) at different velocities (v) and performance level, body size and swimming technique in women. A total of 58 females swimmers were studied. Three performance levels (A, B, C) were determined, ranging from the slower (A) to the faster (B, C). At level C and at 1.1 m.s-1, Cs,1.1 was reduced by 7% when directly compared to level B. The Cs,1.1 was reduced by 10% when calculated per unit of height (h) and by 37% when calculated per unit of h and hydrostatic lift (HL). For the whole group of swimmers, the equation regression was Cs,1.1 = 0.27 h-2.38 HL - 7.5 (r = 0.53, P less than 0.01). To evaluate the specific influence of arm length two groups of long- and short-armed swimmers were selected among swimmers of similar h and performance. The Cs was significantly higher (P less than 0.05) by 12%, SD 2.2%, for short-armed than for long-armed swimmers. To evaluate the influence of different types of swimming technique, two other groups of similar performance and anthropometric characteristics were selected. The Cs was significantly higher (P less than 0.05) by 12%, SD 4.5% for swimmers using for preference their legs rather than their arms. The Cs of the sprinters was 15.7%, SD 2% higher than that of the long distance swimmers. For all groups, Cs increased with v on average by 8% to 11% every 0.1 m.s-1. These findings showed that Cs variations of these women were close to those previously demonstrated for men. The Cs depends on performance level, body size, buoyancy, swimming technique and v. PMID- 1915324 TI - The relationship between anaerobic threshold and electromyographic fatigue threshold in college women. AB - The purpose of this study was to investigate the relationship between anaerobic threshold (Th(an)) and muscle fatigue threshold (EMGFT) as estimated from electromyographic (EMG) data taken from the quadriceps muscles (vastus lateralis) during exercise on a cycle ergometer. The subjects in this study were 20 female college students, including highly trained endurance athletes and untrained sedentary individuals, whose fitness levels derived from their maximal oxygen consumption ranged from 24.9 to 62.2 ml.kg-1.min-1. The rate of increase in integrated EMG (iEMG) activity as a function of time (iEMG slope) was calculated at each of four constant power outputs (350, 300, 250, 200 W), sufficiently high to bring about muscle fatigue. The iEMG slopes so obtained were plotted against the exercise intensities imposed, resulting in linear plots which were extrapolated to zero slope to give an intercept on the power axis which was in turn interpreted as the highest exercise intensity sustainable without electromyographic evidence of neuromuscular fatigue (EMGFT). The Th(an) was estimated from gas exchange parameters during an incremental exercise test on the same cycle ergometer. The mean results indicated that oxygen uptake (VO2) at Than was 1.39 l.min-1, SD 0.44 and VO2 at EMGFT was 1.33 l.min-1, SD 0.57. There was no significant difference between these mean values (P greater than 0.05) and there was a highly significant correlation between VO2 at Than and VO2 at EMGFT (r = 0.823, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915327 TI - EMG power spectra of elbow extensors during ramp and step isometric contractions. AB - The goal of the present study was to compare electromyogram (EMG) power spectra obtained from step (constant force level) and ramp (progressive increase in the force level) isometric contractions. Data windows of different durations were also analysed for the step contractions, in order to evaluate the stability of EMG power spectrum statistics. Fourteen normal subjects performed (1) five ramp elbow extensions ranging from 0 to 100% of the maximum voluntary contraction (MVC) and (2) three stepwise elbow extensions maintained at five different levels of MVC. Spectral analysis of surface EMG signals obtained from triceps brachii and anconeus was performed. The mean power frequency (MPF) and the median frequency (MF) of each power spectrum were obtained from 256-ms windows taken at 10, 20, 40, 60 and 80% MVC for each type of contraction and in addition on 512-, 1024- and 2048-ms windows for the step contractions. No significant differences (P greater than 0.05) were found in the values of both spectral statistics between the different window lengths. Even though no significant differences (P greater than 0.05) were found between the ramp and the step contractions, significant interactions (P less than 0.05) between these two types of contraction and the force level were found for both the MPF and the MF data. These interactions point out the existence of different behaviours for both the MPF and the MF across force levels between the two types of contraction. PMID- 1915326 TI - Early adaptations in gas exchange, cardiac function and haematology to prolonged exercise training in man. AB - In order to determine the effect of short-term training on central adaptations, gas exchange and cardiac function were measured during a prolonged submaximal exercise challenge prior to and following 10-12 consecutive days of exercise. In addition, vascular volumes and selected haematological properties were also examined. The subjects, healthy males between the ages of 19 and 30 years of age, cycled for 2 h per day at approximately 59% of pre-training peak oxygen consumption (VO2) i.e., maximal oxygen consumption (VO2max). Following the training, VO2max (l.min-1) increased (P less than 0.05) by 4.3% (3.94, 0.11 vs 4.11, 0.11; mean, SE) whereas maximal exercise ventilation (VE,max) and maximal heart rate (fc,max) were unchanged. During submaximal exercise, VO2 was unaltered by the training whereas carbon dioxide production (VE) and respiratory exchange ratio were all reduced (P less than 0.05). The altered activity pattern failed to elicit adaptations in either submaximal exercise cardiac output or arteriovenous O2 difference. fc was reduced (P less than 0.05). Plasma volume (PV) as measured by 125I human serum albumin increased by 365 ml or 11.8%, while red cell volume (RCV) as measured by 51chromium-labelled red blood cells (RBC) was unaltered. The increase in PV was accompanied by reductions (P less than 0.05) in haematocrit, haemoglobin concentration (g.100 ml-1), and RBCs (10(6) mm-3). Collectively these changes suggest only minimal adaptations in maximal oxygen transport during the early period of prolonged exercise training. However, as evidenced by the changes during submaximal exercise, both the ventilatory and the cardiodynamic response were altered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915328 TI - Thermoregulatory and subjective responses of clothed men in the cold during continuous and intermittent exercise. AB - Thermoregulatory and thermal subjective responses were studied in ten male, clothed subjects during continuous (C) and intermittent (I) exercise at the same average level of oxygen consumption. The subjects performed both I and C twice, dressed in two different three-layer cold-protective clothing ensembles of two thermal insulation levels [total clothing insulation = 2.59 clo (L) and 3.20 clo (H)]. Experiments were carried out at an ambient temperature of -10 degrees C. Rectal temperatures increased similarly in both types of exercise. Mean skin temperature (Tsk) was lower in I compared to C with both levels of clothing insulation. Over the last 0.5 h of the experiment Tsk was approximately 1.3 degrees C lower in I than in C for clothing L. The skin evaporation rate was higher in clothing H than L but did not differ between I and C. Subjective ratings for thermal sensations of the whole body (BTS) and hands were close to neutral in I and around slightly warm in C. The BTS was lower in I than in C and was lower in L compared to H. It was concluded that, at equal average energy expenditure, thermal responses to intermittent and continuous exercise in the cold differ in clothed subjects, principally as a result of different patterns of heat exchange. PMID- 1915329 TI - In situ NADH laser fluorimetry during muscle contraction in humans. AB - The aim of the present study was to use nicotinamide adenine dinucleotide phosphate, reduced (NADH) fluorimetry, to investigate in situ NADH changes during muscle contraction in humans on an isokinetic dynamometer. Thirteen healthy male subjects each performed one maximal voluntary contraction (MVC) with the knee extensor muscle. The NADH muscle fluorescence was monitored by a double beam laser fluorimeter which uses an optical fibre, percutaneously inserted through a needle into the vastus lateral muscle, to guide the light. The NADH fluorescence was continuously measured at a wavelength of 337 nm. To estimate the haemodynamic artefact, blood backscattering was simultaneously determined at a wavelength of 586 nm. The fluorescence signal was recorded before, during and after contractions at 50% of MVC. The fibre was kept out of contact with the muscle during contractions at 100% of MVC and was only put into contact with it at the end of the contraction. At the onset of contractions at 50% of MVC, NADH fluorescence increased rapidly for 3 s and remained stable thereafter until exhaustion. After a muscle measurement had been made, the optical fibre was put successively into solutions of increasing NADH concentration to ascertain the relationship between the muscle fluorescence signal and the muscle NADH level. This procedure yielded estimated mean values for muscle NADH of 0.172 mmol.kg-1, SEM 0.028 and of 0.184 mmol.kg-1, SEM 0.027 after contractions at 50% and 100% of MVC, respectively, from a resting value of 0.087 mmol.kg-1, SEM 0.015. These results indicated that in situ laser fluorimetry could be used to evaluate NADH changes in humans during muscle contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915330 TI - Strength characteristics of a healthy urban adult population. AB - A random sample of 778 subjects representing ages 25, 35, 45 and 55 years were studied for the amount of habitual physical activity, their anthropometric structure, vertical jumping height, trunk extension and flexion torques and dynamic endurance fitness of trunk extension and flexion. The proportion of subjects who were habitually physically active did not change systematically with age. The highest number of physically inactive subjects was found in men and women in the 35-year age group. The results in all the tests used to assess the strength characteristics were statistically significant when related to sex (P less than 0.001) and in all, except the relative maximal isometric torque of trunk extension, when related to age (P less than 0.001). Everyday physical activity was related to the variation in vertical jumping height (P less than 0.001), as well to the dynamic endurance fitness (P less than 0.001) of trunk extension and flexion. The decline in vertical jumping height and dynamic endurance fitness of trunk extension and flexion fitness was found to start at earlier ages than that of relative maximal isometric trunk extension and flexion torques. Dynamic endurance fitness of trunk flexion showed a more pronounced decline with age than trunk extension fitness. PMID- 1915332 TI - The effect of different blood sampling sites and analyses on the relationship between exercise intensity and 4.0 mmol.l-1 blood lactate concentration. AB - The aim of the study was to examine whether the difference in lactate concentration in different blood fractions is of practical importance when using blood lactate as a test variable of aerobic endurance capacity. Ten male firefighters performed submaximally graded exercise on a cycle ergometer for 20 25 min. Venous and capillary blood samples were taken every 5 min for determination of haematocrit and lactate concentrations in plasma, venous and capillary blood. At the same time, expired air was collected in Douglas bags for determination of the oxygen consumption. A lactate concentration of 4.0 mmol.l-1 was used as the reference value to compare the oxygen consumption and exercise intensity when different types of blood specimen and sampling sites were used for lactate analysis. At this concentration the exercise intensity was 17% lower (P less than 0.01) when plasma lactate was compared to venous blood lactate, and 12% lower (P less than 0.05) when capillary blood lactate was used. Similar discrepancies were seen in oxygen consumption. The results illustrated the importance of standardizing sampling and handling of blood specimens for lactate determination to enable direct comparisons to be made among results obtained in different studies. PMID- 1915331 TI - Effects of supramaximal exercise on blood glucose levels during a subsequent exercise. AB - The purpose of the present investigation was to examine the effects of hyperglycemia induced by supramaximal exercise on blood glucose homeostasis during submaximal exercise following immediately after. Six men were subjected to three experimental situations; in two of these situations, 3 min of high intensity exercise (corresponding to 112, SD 1% VO2max) was immediately followed by either a 60-min period of submaximal exercise (68, SD 2% VO2max) or a 60-min resting period. In the third situation, subjects performed a 63-min period of submaximal exercise only. There were no significant differences between the heart rates, oxygen uptakes, and respiratory exchange ratios during the two submaximal exercise bouts (greater than 15 min) whether or not preceded by supramaximal exercise. The supramaximal exercise was associated within 10 min of the start increases (P less than 0.05) in blood glucose, insulin, and lactate concentrations. This hyperglycemia was more pronounced when subjects continued to exercise submaximally than when they rested (at 7.5 min; P less than 0.05). There was a more rapid return to normal exercise blood glucose and insulin values during submaximal exercise compared with rest. The data show that the hyperinsulinemia following supramaximal exercise is corrected in between 10-30 min during submaximal exercise following immediately, suggesting that this exercise combination does not lead to premature hypoglycemia. PMID- 1915333 TI - The ventilatory threshold gives maximal lactate steady state. AB - The purpose of this study was to examine whether the ventilatory threshold (Thv) would give the maximal lactate steady state ([la]ss, max), which was defined as the highest work rate (W) attained by a subject without a progressive increase in blood lactate concentration [la]b at constant intensity exercise. Firstly, 8 healthy men repeated ramp-work tests (20 W.min-1) on an electrically braked cycle ergometer on different days. During the tests, alveolar gas exchange was measured breath-by-breath, and the W at Thv (WThv) was determined. The results of two-way ANOVA showed that the coefficient of variation of a single WThv determination was 2.6%. Secondly, 13 men performed 30-min exercise at WThv (Thv trial) and at 4.9% above WThv (Thv + trial), which corresponded to the 95% confidence interval of the single determination. The [la]b was measured at 15 and 30 min from the onset of exercise. The [la]b at 15 min (3.15 mmol.l-1, SEM 0.14) and at 30 min (2.95 mmol.l-1, SEM 0.18) were not significantly different in Thv trial. However, the [la]b of Thv + trial significantly increased (P less than 0.05) from 15 min (3.62 mmol.l-1, SEM 0.36) to 30 min (3.91 mmol.l-1, SEM 0.40). These results indicate that Thv gives the [la]ss, max, at which one can perform sustained exercise without continuous [la]b accumulation. PMID- 1915334 TI - The influence of a respiratory acidosis on the exercise blood lactate response. AB - The purpose of the present study was to examine the influence of a respiratory acidosis on the blood lactate (La) threshold and specific blood La concentrations measured during a progressive incremental exercise test. Seven males performed three step-incremental exercise tests (20 W.min-1) breathing the following gas mixtures; 21% O2 balance-nitrogen, and 21% O2, 4% CO2 balance-nitrogen or balance helium. The log-log transformation of La oxygen consumption (VO2) relationship and a 1 mmol.l-1 increase above resting values were used to determine a La threshold. Also, the VO2 corresponding to a La value of 2 (La2) and 4 (La4) mmol.l-1 was determined. Breathing the hypercapnic gas mixtures significantly increased the resting partial pressure of carbon dioxide (PCO2) from 5.6 kPa (42 mm Hg) to 6.1 kPa (46 mm Hg) and decreased pH from 7.395 to 7.366. During the incremental exercise test, PCO2 increased significantly to 7.2 kPa (54 mm Hg) and 6.8 kPa (51 mm Hg) for the hypercapnic gas mixtures with nitrogen and helium, respectively, and pH decreased to 7.194 and 7.208. In contrast, blood PCO2 decreased to 4.9 kPa (37 mm Hg) at the end of the normocapnic exercise test and pH decreased to 7.291. A blood La threshold determined from a log-log transformation [1.20 (0.28) l.min-1] or as an increase of 1 mmol.l-1 [1.84 (0.46) l.min-1] was unaffected by the acid-base alterations. Similarly, the VO2 corresponding to La2 and La4 was not affected by breathing the hypercapnic gas mixtures [2.12 (0.46) l.min-1 and 2.81 (0.52) l.min-1, respectively].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915335 TI - Changes in conduction velocity, median frequency, and root mean square-amplitude of the electromyogram during 25% maximal voluntary contraction of the triceps brachii muscle, to limit of endurance. AB - The objective of the present study was to investigate whether isometric contraction of the right triceps brachii muscle, of maximal duration and at 25% of the maximal voluntary contraction (MVC), would reduce mean fibre conduction velocity (CV) for the active motor units (MU). In addition to the cross correlation of surface electromyograms (EMG) for CV determination, median frequency (fm) and root-mean-square amplitude (rms-amplitude) were calculated. The initial 5 min of the recovery of the three parameters was also investigated. The MVC were performed before and after the sustained contraction. Seven males six in their twenties and one aged 43-participated in the investigation. Mean CV for the unfatigued muscle was 4.5 m.s-1, SD 0.38. On average, CV decreased less than 10% during the sustained contraction (P less than 0.05). The fm decreased almost linearly (46%) during the endurance time, while three quarters of the 250% increase in rms-amplitude took place during the last 50% of the contraction (P less than 0.001, both parameters). The MVC was reduced by 39% immediately after exhaustion (P less than 0.05). During the 1st min of recovery the rms-amplitude decreased by 50%, and the fm increased from 54% to 82% of the initial value (both P less than 0.05). No measurable simultaneous CV restitution occurred. A parallel 15% increase in fm and CV took place during the last 4 min of recovery (both P less than 0.001), while the amplitude remained constant. Since mean CV was essentially unchanged during the last 50% of the endurance time where large changes in fm and rms-amplitude occurred, factors supplementary to CV probably caused the striking changes in fatigue EMG, notably-MU recruitment, synchronization of MU activity, and lowering of MU firing frequencies. Nevertheless, during the last 4 min of recovery the entire increase in fm could be accounted for by the simultaneous increase in CV. PMID- 1915336 TI - Time course of muscle adaptation after high force eccentric exercise. AB - The repeated bout effect on changes in muscle damage indicators was examined in two groups of subjects following two bouts of 70 maximal eccentric actions of the forearm flexors. Fourteen college age female subjects were placed into two groups. The two bouts were separated by 6 weeks (n = 6), and 10 weeks (n = 8). The subjects performed the same amount of work for the bouts. The muscle damage indicators were isometric strength (STR), relaxed elbow joint angle (RANG), flexed elbow joint angle (FANG), perceived muscle soreness ratings (SOR), and plasma creatine kinase activity (CK). These measures were obtained pre-exercise and 5 days following each bout. The first bout showed significant changes in all measures over time for both groups (P less than 0.01). For the 6-week group, significantly smaller changes in RANG (P less than 0.01), SOR (P less than 0.05), and CK (P less than 0.01), as well as significantly faster recoveries (P less than 0.05) for STR and FANG were produced in the second bout. For the 10-week group, significantly smaller changes in RANG (P less than 0.05) and CK (P less than 0.01) were demonstrated by the second bout, but not significant difference was found for STR, FANG, and SOR between bouts 1 and 2. Changes in CK were still significantly smaller than that of the first bout when 6 subjects (3 subjects from each group) performed the same exercise 6 months after the second bout, but no difference in other measures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915337 TI - A. E. Braunstein Plenary Lecture. Nuclear skeleton, DNA domains and control of replication and transcription. AB - Chromosomal DNA is organized in loops or domains of about 100 kb. Their ends seem to be attached to special protein skeletal structures. The DNA-attachment sites can be subdivided into permanent and transient types. The permanent or constitutive attachment sites, which are retained in all types of cells (including those inactive in replication and transcription), either coincide with or are located close to replication origins. This observation provides a simple way for isolation of DNA fragments containing replication origins. Such fragments from the chicken alpha-globin gene domain and other regions of the chicken genome contain DNA sequences which interact with nuclear proteins present in dividing cells, but absent from non-dividing cells. Several new consensus sequences interacting with nuclear proteins were detected. The 5' end region of the alpha globin gene domain containing a replication origin was found to possess enhancer activity lacking tissue specificity. Hence, the domain organization of DNA is related to the organization of replication process. Other sets of data indicate that the integrity of DNA domains is important for maintaining transcription within the domain. According to these data, even a single nick at an distance of about 100 kbp seems to be sufficient for blocking transcription within the whole domain at the stage of RNA elongation. Thus, topological integrity of DNA may be an important factor involved in formation of active chromatin. PMID- 1915338 TI - The discovery of glycogenin and the priming mechanism for glycogen biogenesis. AB - The biogenesis of glycogen in skeletal muscle requires a priming mechanism that has recently been elucidated. The first step is catalysed by a protein tyrosine glucosyltransferase and involves the formation of a novel glycosidic linkage, namely the covalent attachment of glucose to a single tyrosine residue (Tyr194) on a priming protein, termed glycogenin. The next stage is the extension of the glucan chain from Tyr194 and involves the sequential addition of up to seven further glucosyl residues. This reaction is brought about autocatalytically by glycogenin itself, which is a Mn2+/Mg(2+)-dependent UDP-Glc-requiring glucosyltransferase. The glucan primer is elongated by glycogen synthase, but only when glycogenin and glycogen synthase are complexed together. Glycogen synthase dissociates from glycogenin during the synthesis of a glycogen molecule, enabling glycogen molecules to reach their maximum theoretical size. Each mature glycogen beta particle in muscle contains one molecule of glycogenin attached covalently, and an average one glycogen synthase catalytic subunit bound non covalently. As evidence accumulates that a priming protein may be a fundamental property of polysaccharide synthesis in general, the molecular details of mammalian glycogen biogenesis may serve as a useful model for other systems. PMID- 1915339 TI - Primary structure of nuclease P1 from Penicillium citrinum. AB - The primary structure of nuclease P1, which cleaves both RNA and single-stranded DNA, from Penicillium citrinum was elucidated. The complete amino acid sequence consisting of 270 residues was determined by analysis of peptides obtained by digestion with Achromobacter protease I of the reduced and S-aminoethylated protein and by digestion with Staphylococcus aureus V8 protease of the reduced and S-carboxymethylated protein. Four half-cystine residues were assigned to Cys72-Cys217 and Cys80-Cys85. N-Glycosylated asparagine residues were identified at positions 92, 138, 184 and 197. Fast-atom-bombardment and laser-ionization MS were successfully used to confirm the determined amino acid sequences of peptides and to estimate the molecular mass of this glycoprotein having heterogenous sugar moieties, respectively. Comparison of the amino acid sequence of nuclease P1 with other nucleases revealed that the protein has a high degree of sequence identity (50%) with nuclease S1 from Aspergillus oryzae. The His-Phe-Xaa-Asp-Ala sequence (positions 60-64) is similar to the sequence (His-Phe-Asp-Ala) involving the active-site His119 of bovine pancreatic RNase A, and the Pro-Leu-His sequence (positions 124-126) is identical with the sequence involving the active-site His134 of porcine pancreatic DNase I. PMID- 1915340 TI - Differential scanning calorimetric study of carboxypeptidase B, procarboxypeptidase B and its globular activation domain. AB - High-sensitivity differential scanning calorimetry has been applied to the study of porcine pancreatic carboxypeptidase B, the proenzyme and its 81-residue activation domain. The thermal study has been carried out over a range of scan rates, ionic strengths and pH values. The thermal unfolding of the isolated activation domain has been found to be reversible and corresponds to that of a typical compact globular structure, with melting temperatures higher than those of the enzyme and proenzyme. Both proteins, on the other hand, undergo an irreversible, highly scan-rate-dependent thermal denaturation under all the experimental conditions investigated. The denaturation of the enzyme at pH 7.5 and the proenzyme at pH 7.5 and 9.0 follows the two-state irreversible model [Sanchez-Ruiz, J.M., Lopez-Lacomba, J.L., Cortijo, M. & Mateo, P.L. (1988) Biochemistry 27, 1648-1652]. Thus the kinetic constants and activation parameters of the denaturation process could be obtained and compared to those for other proteins, particularly those of the closely related carboxypeptidase A system. PMID- 1915342 TI - Heat-shock response of rat hepatoma variant cells. AB - The effect of mild heat shock on protein synthesis was examined in differentiated and dedifferentiated, glucocorticoid-sensitive and resistant clones of H4IIEC3 rat hepatoma cells by one- and two-dimensional gel electrophoresis of [35S]methionine-labeled proteins. Among the major heat-shock proteins, five were induced in all hepatoma clones. Certain members of the HSP70 family and the corresponding mRNAs were only slightly inducible in the glucocorticoid-resistant variants, but were strongly inducible in the sensitive ones. Three other proteins lacked heat inducibility in the dedifferentiated clones. The constitutive level of one major heat-shock protein was elevated in all dedifferentiated variants. These results show that the stage of differentiation influences the expression of heat-shock genes of hepatoma cells. We found no correlation between the elevated constitutive or induced level of heat-shock proteins and heat resistance. PMID- 1915341 TI - Protein-kinase-C-independent activation of arachidonate release and prostaglandin E2 formation in macrophages interacting with certain bacteria. AB - Certain bacterial species, of which we selected Fusobacterium nucleatum, Gardnerella vaginalis, Peptostreptococcus anaerobius and Propionibacterium acnes, were found to induce release of arachidonic acid in a dose- and time-dependent manner in mouse macrophages. The release of arachidonic acid showed a characteristic lag period of approximately 10 min and was accompanied by selective transformation into prostaglandin E2. Bacteria killed by various methods caused a similar response, indicating that bacterial surface structures rather than secreted products were involved. Down-regulation of protein kinase C by treatment of macrophages with 4 beta-phorbol 12-myristate 13-acetate hardly affected the response to bacteria at all, except for a partial inhibition in the case of P. acnes. Furthermore, the generation of prostaglandin E2 was synergistically enhanced when macrophages were exposed to both bacteria and phorbol ester. It is also unlikely that bacterial activation was mediated exclusively via a rise in cytosolic [Ca2+], since bacteria stimulated the release of arachidonic acid also when [Ca2+] was clamped at various levels and since the response to bacteria was enhanced in an additive to synergistic manner when combined with calcium ionophore. Changes in protein phosphorylation in macrophages exposed to F. nucleatum (Gram-negative) were virtually identical to those seen with bacterial lipopolysaccharide, while P. anaerobius (Gram-positive) induced enhanced labeling of a single detectable phosphoprotein. In both cases, the changes in protein phosphorylation showed a time lag of 4-8 min and occurred independently of protein kinase C, consistent with a possible role in signal transduction. These results demonstrate that certain bacteria cause activation of arachidonic acid release and prostaglandin E2 formation in mouse macrophages; that the response is independent of protein kinase C and that it is not wholly mediated via a rise in cytosolic [Ca2+]. PMID- 1915343 TI - Formation of nucleophosmin/B23 oligomers requires both the amino- and the carboxyl-terminal domains of the protein. AB - Nucleophosmin/B23 is a nucleolar phosphoprotein which forms oligomers. To determine the domain essential for oligomer formation, various deletion and point mutation clones of nucleophosmin/B23 were constructed. Nucleophosmin/B23 and the mutant proteins were produced by (a) coupled in vitro transcription and translation and (b) expression in Escherichia coli with T7 RNA polymerase expression vector (pET-8c). Nucleophosmin/B23 synthesized in vitro has the same peptide map as that synthesized in HeLa cells. Similarly, it formed oligomers which could be detected in SDS/PAGE and were cross-linked with nitrogen mustard in vivo. Substitution of Met5, Met7, and Met9 with Leu or deletion of five amino acids at the C-terminus abolished the oligomerization. Deletion of portions of amino acids in the middle of the molecule (amino acid residues 83-152, 117-186 and 185-240) had little effect on the oligomerization. Co-expression of the N- and C-terminal mutant clones in vitro did not produce oligomers. These results indicate that intra-molecular interactions with both the N- and C-terminal domains are essential for oligomer formation. PMID- 1915344 TI - Proteolytic cleavage sites in smooth muscle myosin-light-chain kinase and their relation to structural and regulatory domains. AB - Proteolysis of the smooth muscle myosin-light-chain kinase with either thermolysin or endoproteinase Lys-C cleaves the enzyme towards the amino-terminus between the first and second unc domains, unc-II-1 and unc-II-2, and in the calmodulin-binding domain. The thermolytic fragment extends 532 residues from Ser275 to Ala806 and is resistant to further digestion. It is catalytically inactive and does not bind calmodulin. Further proteolysis of the thermolytic fragment with trypsin generates a constitutively active fragment. Digestion with endoproteinase Lys-C initially results in an inactive fragment of 516 residues, Ala287 to Lys802. Further digestion with Lys-C endoproteinase results in a constitutively active 474-residue fragment with the same amino-terminus, but a carboxyl-terminus at Lys760, near Arg762, the last conserved residue of protein kinase catalytic domains. There is no cleavage in the acidic-residue-rich connecting peptide between the amino-terminus of the catalytic domain and the unc I domain, nor within the unc-II or unc-I domains or between the adjacent unc-II-2 and unc-I domains. The pattern of cleavages by these proteases reflects well the predicted domain structure of the myosin-light-chain kinase and further delineates the regulatory pseudosubstrate region. A synthetic peptide corresponding to the pseudosubstrate sequence, MLCK(787-807) was a more potent inhibitor by three orders of magnitude than the overlapping peptide MLCK(777-793) proposed by Ikebe et al. (1989) [Ikebe, M., Maruta, S. & Reardon, S. (1989) J. Biol. Chem. 264, 6967-6971] to be important in autoregulation of the myosin-light chain kinase. PMID- 1915345 TI - NMR studies on p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens and salicylate hydroxylase from Pseudomonas putida. AB - p-Hydroxybenzoate hydroxylase from Pseudomonas fluorescens and salicylate hydroxylase from Pseudomonas putida have been reconstituted with 13C- and 15N enriched FAD. The protein preparations were studied by 13C-NMR, 15N-NMR and 31P NMR techniques in the oxidized and in the two-electron-reduced states. The chemical shift values are compared with those of free flavin in water or chloroform. It is shown that the pi electron distribution in oxidized free p hydroxybenzoate hydroxylase is comparable to free flavin in water, and it is therefore suggested that the flavin ring is solvent accessible. Addition of substrate has a strong effect on several resonances, e.g. C2 and N5, which indicates that the flavin ring becomes shielded from solvent and also that a conformational change occurs involving the positive pole of an alpha-helix microdipole. In the reduced state, the flavin in p-hydroxybenzoate hydroxylase is bound in the anionic form, i.e. carrying a negative charge at N1. The flavin is bound in a more planar configuration than when free in solution. Upon binding of substrate the resonances of N1, C10a and N10 shift upfield. It is suggested that these upfield shifts are the result of a conformational change similar, but not identical, to the one observed in the oxidized state. The 13C chemical shifts of FAD bound to apo(salicylate hydroxylase) indicate that in the oxidized state the flavin ring is also fairly solvent accessible in the free enzyme. Addition of substrate has a strong effect on the hydrogen bond formed with O4 alpha. It is suggested that this is due to the exclusion of water from the active site by the binding of substrate. In the reduced state, the flavin is anionic. Addition of substrate forces the flavin ring to adopt a more planar configuration, i.e. a sp2 hybridized N5 atom and a slightly sp3-hybridized N10 atom. The NMR results are discussed in relation to the reaction catalyzed by the enzymes. PMID- 1915346 TI - A fluorescence spectroscopic study of glutaminyl-tRNA synthetase from Escherichia coli and its implications for the enzyme mechanism. AB - Interaction between Escherichia coli glutaminyl-tRNA synthetase (GlnRS) and its substrates have been studied by fluorescence quenching. In the absence of other substrates, glutamine, tRNA(Gln) and ATP bind with dissociation constants of 460, 0.22 and 180 microM, respectively. The presence of other substrates has either no effect or, at best a weak effect, on binding of ligands. Attempts to isolate enzyme-bound aminoacyl adenylate did not succeed. Binding of the phosphodiester, 5'-(methyl)adenosine monophosphate (MeAMP), to GlnRS was studied by fluorescence quenching and radioactive-ligand binding. tRNA also only has a weak effect on phosphodiester binding. Selectively pyrene-labeled GlnRS was used to obtain shape and size information for free GlnRS. A comparison with the GlnRS shape in the GlnRS/tRNA(Gln) crystal structure indicates that no major change in shape and size occurs upon tRNA(Gln) binding to GlnRS. 5,5'-Bis(8-anilino-1-naphthalene sulfonate) (bis-ANS), a non-covalent fluorescent probe, was also used to probe for conformational changes in GlnRS. This probe also indicated that no major conformational change occurs upon tRNA(Gln) binding. We conclude that lack of tRNA-independent pyrophosphate-exchange activity in this enzyme is not a result of either lack of glutamine or ATP binding in the absence of tRNA, or formation of aminoacyl adenylate and slow release of pyrophosphate. A conformational change is implied upon tRNA binding, which promotes pyrophosphate exchange. Fluorescence studies indicate that this conformational change must be limited and local in nature. PMID- 1915348 TI - Preparation and kinetic properties of 5-ethylphenazine-glucose-dehydrogenase-NAD+ conjugate, a semisynthetic glucose oxidase. AB - 5-Ethylphenazine-glucose-dehydrogenase-NAD+ conjugate (EP(+)-GlcDH-NAD+) was prepared by linking both poly(ethylene glycol)-bound 5-ethylphenazine and poly(ethylene glycol)-bound NAD+ to glucose dehydrogenase. The average number of the ethylphenazine moieties bound/enzyme subunit was 0.8, and that of the NAD+ moieties was 1.2. This conjugate is a semisynthetic enzyme having glucose oxidase activity using oxygen or 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) as an electron acceptor. When the concentration of oxygen or MTT is varied, the oxidase activity fits the Michaelis-Menten equation with the following values of the kinetic constants: for the system with oxygen, the turnover number per subunit is 0.40 s-1 and Km for oxygen is 1.57 mM; and for the system with MTT, the turnover number is 0.11 s-1 and Km for MTT is 0.072 mM. The catalytic cycle of the semisynthetic oxidase has two catalytic steps: reduction of the NAD+ moiety by the active site of the glucose dehydrogenase moiety and oxidation of the NADH moiety by another catalytic site of the ethylphenazine moiety. The apparent intramolecular rate constants of these steps were estimated, and the values are as follows: 0.39 s-1 for the reductions of the NAD+ moiety, 2.2 s-1 and 0.12 s-1 for the oxidation of the NADH moiety in the systems with oxygen and with MTT, respectively, and 3.2 s-1 and 0.18 s-1 for the reduction of the ethylphenazine moiety in the systems with oxygen and with MTT, respectively. On the bases of these results, the following three rate acceleration mechanisms of the semisynthetic glucose oxidase are discussed: high effective concentration, intramolecular coupling of successive catalytic reactions, and multiple connection between the two kinds of the catalytic sites. PMID- 1915347 TI - Pterocarpan phytoalexin biosynthesis in elicitor-challenged chickpea (Cicer arietinum L.) cell cultures. Purification, characterization and cDNA cloning of NADPH:isoflavone oxidoreductase. AB - NADPH:isoflavone oxidoreductase (IFR) is the first soluble enzyme of the pterocarpan-specific part of phytoalexin biosynthesis in chickpea (Cicer arietinum L.). The enzyme was purified to apparent homogeneity by a five-step procedure from chickpea cell cultures treated with yeast extract as elicitor. Analysis by gel filtration and SDS/PAGE showed that the enzyme consists of a single polypeptide with a molecular mass of 36 kDa. Km values for the substrates 2'-hydroxyformononetin, 2'-hydroxypseudobaptigenin and NADPH were 6, 6 and 20 microM, respectively. The IFR showed pronounced specificity for the substitution pattern of isoflavones. We found a 2'-hydroxy group and a 4',5'-methylenedioxy or 4'-methoxy function to be essential for acceptance as substrate. The isoelectric point of the protein was determined as 6.3 by IEF and there is no evidence for the existence of isoenzymes. Partial amino acid sequences of IFR were determined from internal peptides obtained by tryptic digestion of the protein and corresponding oligonucleotides were synthesized. A lambda gt10 cDNA library was constructed using poly(A)-rich RNA isolated from chickpea cell cultures treated with Ascochyta rabiei elicitor. 150 positive clones were obtained by screening 2 x 10(5) clones with an IFR-specific oligonucleotide. The identity of sequenced clones was confirmed by comparison of the deduced amino acid sequence with the internal peptide sequences of purified IFR. The sequence of a 1183-bp clone contained a continuous open reading frame of 954 bases encoding a polypeptide of 318 amino acids with a calculated molecular mass of 35.4 kDa, indicating that a full-length cDNA coding for IFR was isolated. PMID- 1915350 TI - Characterization of two pterin derivatives isolated from Methanoculleus thermophilicum. AB - Methanoculleus thermophilicum was shown to contain two pterin derivatives. The structures of these pterin derivatives were established from amino acid analysis, 1H-NMR and fast-atom bombardment mass spectrometry data. One of the pterins was identified as tatiopterin-O, an aspartyl derivative of methanopterin with a proton at position 7 of the pterin moiety. The other pterin, which we named thermopterin, differed in the structure of the aniline group, containing two additional hydroxyl residues. The IUPAC name of thermopterin is N-[-1'-(2"-amino 4"-hydroxy-6"-pteridinyl)ethyl]-4- [2',3',4',5'-tetrahydroxypent-1'-yl(5'----1") O-alpha-ribofuranosyl-5"-phosphoric acid]-2,5-dihydroxyaniline, in which the phosphate group is esterified with alpha-hydroxyglutarylaspartic acid. PMID- 1915349 TI - Investigation of the structure of lipid A from Actinobacillus actinomycetemcomitans strain Y4 and human clinical isolate PO 1021-7. AB - The lipopolysaccharides of Actinobacillus actinomycetemcomitans strain Y4 and a human clinical isolate PO 1021-7 were examined by SDS/PAGE, deoxycholate/PAGE and mass spectrometry. PAGE analysis revealed an electrophoretic pattern similar to the SR-type lipopolysaccharide (LPS) of Salmonella. Deoxycholate/PAGE indicated the LPS of A. actinomycetemcomitans to consist of short sugar chains. Chemical analysis revealed the presence of thiobarbituric-acid-positive material (3-deoxy D-manno-octulosonic acid equivalents) and four neutral sugars: glucose, galactose, D-glycero-D-manno-heptose and L-glycero-D-manno-heptose. Phosphate, glucosamine, glycine, and the fatty acids, 3-hydroxymyristic acid, myristic acid and palmitic acid, comprised the remainder of the molecule. The structure of the free lipid A revealed it to consist of a 1,6-glucosamine disaccharide esterified at C4' by a phosphomonoester. The hydroxyl group at C3 and the amide group of the non-reducing glucosamine were both acylated by 3-myristoylmyristic acid; analogous sites on the reducing glucosamine were acylated by 3-hydroxymyristic acid. Hydroxyl groups at C4 and C6' in the free lipid A were unsubstituted, with C6 being the proposed attachment site of the polysaccharide moiety. Chemical analysis revealed the presence of glycine in the intact LPS; its exact location in the A. actinomycetemcomitans LPS is still to be determined. Both intact LPS and free lipid A were highly lethal to galactosamine-sensitized mice, comparable to that of Salmonella. PMID- 1915351 TI - Adaptive regulation of Na(+)-dependent phosphate transport in the bovine renal epithelial cell line NBL-1. Identification of the phosphate transporter as a 55 kDa glycoprotein. AB - 1. Na(+)-dependent phosphate transport activity from bovine brush border membrane vesicles (BBMV) was reconstituted into artificial phospholipid membranes. It was shown, using lectin affinity chromatography, that transport activity was mediated by a glycoprotein. 2. The bovine kidney epithelial cell line NBL-1 expresses a Na(+)-dependent phosphate transporter which shows adaptive regulation in response to various media phosphate concentrations. Cells incubated in low-phosphate medium and medium containing 10 mM phosphate have Vmax values of 6.34 +/- 0.18 and 2.95 +/- 0.1 nmol.mg-1.3 min-1 and Km values of 17.1 +/- 3.0 and 36.3 +/- 7.14 microM for phosphate transport, respectively. Thus there is a significant (P less than 0.001) decrease in the Km and increase in the Vmax of transport when cells are transferred from 10 mM phosphate medium to low-phosphate medium. 3. Adaptation of phosphate transport in NBL-1 cells to low-phosphate medium was abolished by tunicamycin, an inhibitor of protein glycosylation, indicating that the transporter in these cells, like that in bovine BBMV, is a glycoprotein. 4. Cells were adapted to low-phosphate medium in the presence of [3H]mannose. Under these conditions a single membrane protein of molecular mass 55 kDa was labelled in the absence but not the presence of tunicamycin. Little labelling occurred if the cells were maintained in high-phosphate medium. 5. On the basis of these observations, it is proposed that the phosphate transporter of NBL-1 cells is a 55-kDa glycoprotein. Phosphate is accumulated across the brush border membrane of renal proximal tubule cells via a Na+/phosphate cotransport system. Na(+) dependent phosphate transport has been extensively studied in isolated brush border membrane vesicles from rabbit and rat kidney [1-3]. The symport of phosphate and Na+ is electroneutral with a stoichiometry of 2Na+/phosphate at physiological pH values. PMID- 1915352 TI - Expression and characterization of protein kinase C-delta. AB - A cDNA encoding protein kinase C-delta (PKC-delta) was isolated from a rat brain library. The coding region was subcloned into the expression vector pmt2 and transfected into COS-1 cells. Expression of the protein led to an 11-fold increase in activity as determined with a synthetic peptide based on the PKC delta pseudosubstrate site. The Mr of PKC-delta as determined by SDS/PAGE and immunoblot analysis using anti-(PKC-delta C-terminal) antibodies was 77,000. The enzyme was purified to near homogeneity and showed total dependency on phospholipid and diacylglycerol (or phorbol esters) for activity. Like PKC epsilon, PKC-delta displays no Ca2+ dependence for activation. The substrate specificity of PCK-delta is similar to that of PKC-epsilon but quite different from other PKCs. PMID- 1915353 TI - Retraction concerning amino acid sequence of a 12-kDa inhibitor of protein kinase C. Mistaken identity of a protein kinase C inhibitor. PMID- 1915354 TI - Mathematical analysis of enzymic reaction systems using optimization principles. PMID- 1915355 TI - Structural analysis of the entire proopiomelanocortin gene of Xenopus laevis. AB - In the pars intermedia of the pituitary the prohormone proopiomelanocortin (POMC) is tissue-specifically processed to, among other peptides, alpha-melanotropin (alpha MSH). In the South African clawed toad Xenopus laevis this hormone mediates the process of background adaptation: release of alpha-MSH causes darkening of the animal, while inhibition of alpha-MSH release results in a pale toad. Elevated release of alpha-MSH coincides with a higher rate of POMC gene transcription. The present study aims to find possible transcriptional regulatory elements in the Xenopus POMC gene. For that purpose the complete nucleotide sequence of the POMC gene and its 5'- and 3'- flanking regions were determined and analyzed. The Xenopus POMC gene promoter contains several regions which may be regulatory DNA elements in view of their similarity with corresponding regions of mammalian POMC gene promoters. In the rat POMC gene promoter, many of these regions represent protein-binding sequences. Besides the promoter sequence and the protein-coding sequences, no other segments with significant identity between the Xenopus and human POMC genes were found. Intron A of the Xenopus POMC gene contains a simple sequence, (TATC)76, and a JH12 repetitive element, while the 3' flanking region contains a repetitive-EcoRI-monomer-2 element. Comparison of the JH12 sequence of the POMC gene with JH12 sequences from other Xenopus genes revealed a 335-bp consensus sequence which is flanked by a 30-bp inverted repeat. This JH12 consensus sequence is significantly larger than the previously reported JH12 core region. Alignment of intron B of the Xenopus POMC gene with database sequences revealed a consensus sequence of a novel Xenopus repetitive element of 330 bp flanked by a nearly perfect inverted repeat, indicating that this element may be a transposon-like element. PMID- 1915356 TI - A 60-kDa protein from rabbit reticulocytes specifically recognizes the capped 5' end of beta-globin mRNA. AB - The binding of proteins from rabbit reticulocyte lysate to in-vitro-generated beta-globin mRNA and its defined segments was investigated using ultraviolet cross-linking experiments as well as gel-retardation assays. Under stringent conditions, only three proteins (72, 60 and 50 kDa) were found associated with full-length beta-globin mRNA at different positions. The 72-kDa protein is most likely the poly(A)-binding protein and binds, as expected, to the poly(A) tail, whereas the 50-kDa protein exhibits affinity for the trailer region of beta globin mRNA. The binding region of the 60-kDa protein is located at the 5' end of beta-globin mRNA. The interaction of this protein is dependent on the presence of the 5' cap structure, as indicated by competition experiments using an uncapped beta-globin-mRNA leader segment. Further competition experiments with beta-globin mRNA, deleted in part in the leader region, suggest that, besides the cap structure, certain sequence elements are necessary for the interaction of the 60 kDa protein and the beta-globin mRNA leader. PMID- 1915357 TI - The polymerase domain of Streptococcus pneumoniae DNA polymerase I. High expression, purification and characterization. AB - The 3'-terminal two-thirds of the Streptococcus pneumoniae polA gene was cloned in an Escherichia coli genefusion vector with inducible expression. The resulting recombinant plasmid (pSM10) directs the hyperproduction of a polypeptide of 70.6 kDa corresponding to the C-terminal fragment of pneumococcal DNA polymerase I. Induced cells synthesized catalytically active protein to the extent of 7% of the total soluble protein in the cells. The polymerase fragment was purified to greater than 90% homogeneity with a yield of 1.5 mg pure protein/l culture. The protein has DNA polymerase activity, but no exonuclease activity. The enzyme requires a divalent cation (MgCl2 or MnCl2) for polymerization of DNA. Comparison of the mutant and wild-type pneumococcal polymerases shows that the construction did not affect the enzymatic affinity for the various substrates. The mutant protein, like its parent DNA polymerase I, exhibited an intermediate level of activity with primed single-stranded DNA. At high molar ratio of enzyme/DNA substrate, the polymerase fragment catalyzes strand displacement and switching after completing the replication of a primed single-stranded M13 DNA molecule. PMID- 1915358 TI - An amplified insect dihydrofolate reductase gene contains a single intron. AB - We have used methotrexate-resistant mosquito (Aedes albopictus) cells as the source of DNA for cloning an 8.5-kb EcoRI fragment containing an amplified dihydrofolate reductase (DHRF) gene. An estimated 1200 copies of the DHFR gene were represented in nuclear DNA from Mtx-5011-256 cells, which were 3000-fold more resistant to methotrexate than wild-type cells. Southern blot analysis indicated that all of the amplified DHFR genes were contained within a 1.8-kb AccI fragment represented in the cloned DNA. In contrast to mammalian DHFR genes which span approximately 30 kb, the complete amino acid coding sequence of the mosquito DHFR gene spanned 614 nucleotides, including a single 56-nucleotide intron that interrupted a conserved Arg codon at amino acid position 27. Additional introns characteristic of mammalian DHFR genes were absent; conservation of the first intron in the mosquito DHFR gene supports a regulatory role for this intron. The mosquito DHFR gene coded for a 186-amino-acid protein with 43-48% similarity to vertebrate DHFR. PMID- 1915359 TI - The lux genes of the luminous bacterial symbiont, Photobacterium leiognathi, of the ponyfish. Nucleotide sequence, difference in gene organization, and high expression in mutant Escherichia coli. AB - The lux genes required for light expression in the luminescent bacterium Photobacterium leiognathi (ATCC 25521) have been cloned and expressed in Escherichia coli and their organization and nucleotide sequence determined. Transformation of a recombinant 9.5-kbp chromosomal DNA fragment of P. leiognathi into an E. coli mutant (43R) gave luminescent colonies that were as bright as those of the parental strain. Moreover, expression of the lux genes in the mutant E. coli was strong enough so that not only were high levels of luciferase detected in crude extracts, but the fatty-acid reductase activity responsible for synthesis of the aldehyde substrate for the luminescent reaction could readily be measured. Determination of the 7.3-kbp nucleotide sequence of P. leiognathi DNA, including the genes for luciferase (luxAB) and fatty-acid reductase (luxCDE) as well as a new lux gene (luxG) found recently in luminescent Vibrio species, showed that the order of the lux genes was luxCDABEG. Moreover, luxF, a gene homologous to luxB and located between luxB and luxE in Photobacterium but not Vibrio strains, was absent. In spite of this different lux gene organization, an intergenic stem-loop structure between luxB and luxE was discovered to be highly conserved in other Photobacterium species after luxF. PMID- 1915360 TI - Molecular symmetry and arrangement of subunits in extracellular hemoglobin from the nematode Ascaris suum. AB - The arrangement of subunits and molecular symmetry of extracellular hemoglobin from the nematode Ascaris suum, an 11.7S molecular of molecular mass 332 kDa and composed of eight identical subunits, was studied. Dissociation of the molecule at alkaline and acid pH yielded 4.6S and 2.7S components, identified as polypeptide-chain dimers and monomers, respectively. Cross-linking with glutardialdehyde followed by SDS/PAGE resulted in a maximum number of eight bands identified in order of decreasing mobility as monomeric and 2-8 cross-linked polypeptide-chain species. Comparison with values predicted from theory shows that the distribution of protein among the various cross-linked species, obtained after different extents of exposure to cross-linker, is consistent with a two layered arrangement of subunits involving one type of interaction between subunits from different layers and another between subunits within the same layer. Electron micrographs of the molecule showed two profiles, a square and a rectangle. We propose a model for the molecule which is eight subunits arranged in two layers, stacked in an eclipsed orientation. The proposed model is consistent with the results from sedimentation, cross-linking and electron microscopy. Taken together, our findings indicate D4 symmetry for Ascaris hemoglobin. PMID- 1915361 TI - Possible involvement of Lys603 from Escherichia coli glucosamine-6-phosphate synthase in the binding of its substrate fructose 6-phosphate. AB - Pyridoxal 5'-phosphate is a competitive inhibitor of glucosamine-6-phosphate synthase with respect to the substrate fructose 6-phosphate. Irreversible inactivation of pyridoxal-5'-phosphate-treated enzyme with [14C]-cyanide resulted in covalent incorporation of close to 1 mol pyridoxal 5'-phosphate/mol enzyme subunit. The enzyme-pyridoxal-5'-phosphate complex could also be inactivated by reduction with NaBH3CN. Sequence analysis of the unique radioactively labelled tryptic peptide, resulting from inactivation with [3H]NaBH3CN, identified the C terminal nonapeptide encompassing the modified Lys603. The presence of fructose 6 phosphate protected this residue from pyridoxylation. Direct evidence that a lysine residue is involved in the binding of the substrate as a Schiff base came from the isolation at 4 degrees C of a enzyme-fructose-6-phosphate complex in a 1:1 molar ratio. Treatment of the enzyme-[14C]fructose-6-phosphate complex with NaBH3CN revealed one site of modification in the tryptic peptide map. In contrast, trapping the same complex with potassium cyanide resulted in the isolation of several radiolabelled peptides containing lysines which could potentially bind fructose 6-phosphate. However, since the radioactivity was not specifically associated with the lysine residues, it is suggested that these 14C labelled peptides resulted from the decomposition of an unstable alpha,alpha' dihydroxyaminonitrile adduct rather than from a lack of specificity of fructose 6 phosphate fixation. Lys603 is then the candidate of choice for fructose 6 phosphate binding since it lies at or near the active site as demonstrated by the trapping experiments with pyridoxal 5'-phosphate described above, and among the lysines which belong to the sugar-binding domain this is the only one conserved between the three members of the purF, glutamine-dependent, amidotransferase subfamily which include the glucosamine-6-phosphate synthase from Escherichia coli, Saccharomyces cerevisiae and the Rhizobium nodulation protein NodM. PMID- 1915362 TI - The conformation of porcine-brain natriuretic peptide by two-dimensional NMR spectroscopy. AB - Two-dimensional (2D) 1H-NMR spectra of porcine-brain natriuretic peptide (pBNP) have been recorded at 300 MHz and 400 MHz. Peak assignments have been made and the combined information from chemical shifts, coupling constants, temperature coefficients and NOEs have been used to determine the conformational properties of pBNP in (C2H3)2SO. Overall the peptide appears to be flexible, with the possibility of some beta-type structure near the C terminus. Some of the assignments and deduced structural features in the current study differ from those in a recent report by Inooka et al. [Inooka, H., Kikuchi, T., Endo, S., Ishibashi, Y., Wakimasu, M. and Mizuta, E. (1990) Eur. J. Biochem. 193, 127-134] which may indicate the sensitivity of the structure of this peptide to differences in solution conditions. PMID- 1915363 TI - Yolk protein in leech. Identification, purification and characterization of vitellin and vitellogenin. AB - Theromyzon tessulatum vitellin was identified as a lipoglycoprotein of 490 kDa. The insolubility of this molecule in low-ionic-strength media was used to extract it from the ovaries. Antiserum prepared against vitellin was shown to react with a coelomic fluid component of 520 kDa. This vitellin precursor, or vitellogenin, was purified by gel permeation and ion-exchange column chromatography. These two lipoglycoproteins were characterized by amino acid, carbohydrate and lipid analysis and subunit composition. In spite of differences in terms of native molecular mass, solubility and isoelectric point, the lipoglycoproteins isolated from the coelomic fluid and the ovary were similar in their subunit components (a single polypeptide of 165 kDa) and in their amino acid and carbohydrate compositions. However, vitellogenin was found to be more highly lipidated (31.8% by mass) than vitellin (24% by mass) and lipid analysis indicated a higher amount of sterols and phospholipids in vitellogenin. From these data, we conclude that vitellogenin and vitellin are probably dimers of two identical subunit polypeptides plus lipid and that, after vitellogenin is sequestered in the oocyte, part of its lipid component is stripped from the molecule to give vitellin. Furthermore, electrophoretic analysis seems to indicate that vitellogenin synthesis and secretion is initiated following the third and last blood meal of the animal but that vitellogenin significantly accumulates in the coelomic fluid before being incorporated in the oocytes suggesting a complex mode of vitellogenesis regulation. PMID- 1915365 TI - Sequence-specific 1H-NMR assignments and secondary structure of the lipoyl domain of the Bacillus stearothermophilus pyruvate dehydrogenase multienzyme complex. AB - The lipoyl domain (residues 1-85) of the lipoate-acetyltransferase polypeptide chain of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus has been subjected to detailed structural analysis by means of two-dimensional (2D) 1H-NMR spectroscopy at 400 MHz. Sequence-specific proton resonance assignments were made, but at this field strength not all of the side chain protons could be assigned, especially from complex spin systems like those of leucine, proline and lysine residues. Measurement of short-range interproton distances identified two extensive regions of beta-sheet, each containing four anti-parallel peptide strands. The lipoyl-lysine residue (Lys42) is located in a tight turn at a corner of one sheet, the N-terminal and C-terminal residues of the domain are close together in two adjacent beta-strands in the other. The lipoylated and unlipoylated forms of the domain have almost identical spectra, indicating that there is little, if any, conformational change in the protein as a result of the post-translational modification. PMID- 1915364 TI - Crystal structure of the Tyr45Trp mutant of ribonuclease T1 in a complex with 2' adenylic acid. AB - The recombinant Tyr45Trp mutant of Lys25-ribonuclease T1 was overexpressed and purified from an Escherichia coli strain. The mutant enzyme, which shows reduced activity towards GpA and increased activity towards pGpC, pApC and pUpC compared with wild-type RNase T1, was co-crystallized with 2'-adenylic acid by microdialysis. The space group is P212121 with unit cell dimenions a = 4.932(2), b = 4.661(2), c = 4.092(1) nm. The crystal structure was solved using the coordinates of the isomorphous complex of wild-type RNase T1 with 2'-AMP. The refinement was based on Fhkl of 7726 reflexions with Fo greater than or equal to 1 sigma (Fo) in the resolution range of 2.0-0.19 nm and converged with an R factor of 0.179. The adenosine of 2'-AMP is not bound to the guanosine binding site, as could be expected from the mutation of Tyr45Trp, but is stacked on the Gly74 carbonyl group and the His92 imidazole group which form a subsite for substrate binding, as already observed in the wild-type 2'-AMP complex. The point mutation of Tyr45Trp does not perturb the backbone conformation and the Trp indole side chain is in a comparable position to the phenolic Tyr45 of the wild type enzyme. PMID- 1915366 TI - Microcalorimetric investigation of the interactions between the subunits of the bovine pancreatic procarboxypeptidase A-S6 complex. AB - A complete microcalorimetric investigation of the interactions between the native subunits of the bovine pancreatic procarboxypeptidase A-S6 ternary complex has been performed. All the association constants and thermodynamic parameters associated with the reactions forming the various complexes have been determined. The influence of pH and ionic strength on the binding reactions has been investigated. Interestingly, the affinity between the subunits is not significantly modified by varying the ionic strength. In this respect, an enthalpy/entropy compensatory effect is observed for the binding of subunit III to subunit I when the ionic strength is increased, suggesting a physiological function for the association. The various pathways for formation of the ternary complex have been studied. Binding of subunit II (or III) to subunit I, the central element of the ternary complex, does not significantly modify the affinity of the other subunit for subunit I. From a thermodynamic point of view, the same final state is obtained whatever the pathway of ternary complex formation. This study is the first step of a kinetic investigation of the associated subunits. PMID- 1915367 TI - Non-random conformation of a mouse IgG2a monoclonal antibody at low pH. AB - The pH dependence of the conformation of a mouse IgG2a, kappa monoclonal antibody (MN12) was investigated by several physical techniques, including fluorescence spectroscopy, near-ultraviolet and far-ultraviolet CD, and electric-field-induced transient birefringence measurements. The intensity of the intrinsic tryptophan fluorescence remained constant in the pH range from 3.5 to 10.0. A conformational alteration in the MN12 molecule was observed in the pH region between pH 3.5 and 2.5, as reflected by a substantial enhancement of the fluorescence quantum yield. This effect was more pronounced at high ionic strengths. The fluorescence emission was unaltered, indicating that the acid-induced conformational state is different from a completely unfolded state. This was confirmed by CD and fluorescence polarisation measurements. Iodide and acrylamide fluorescence quenching studies indicated a gradually increasing accessibility of MN12 tryptophan residues with decreasing pH. At low pH precipitation was observed in the presence of iodide. One rotational relaxation time (0.16-0.18 microseconds) was observed for MN12 by electric-field-induced transient birefringence measurements at low ionic strength. After exposure of MN12 to low pH for 1 h, the relaxation time was increased to 0.23 microseconds; a further increase to 0.30 microseconds was observed after 24 h. The combined results suggest an acid induced expansion and enhanced flexibility of MN12, which eventually leads to irreversible aggregation. PMID- 1915368 TI - Cell-free immunity in Cecropia. A model system for antibacterial proteins. PMID- 1915369 TI - Identification of the cDNA clone which encodes the 58-kDa protein containing the amino acid sequence of rat liver non-specific lipid-transfer protein (sterol carrier protein 2). Homology with rat peroxisomal and mitochondrial 3-oxoacyl-CoA thiolases. AB - The relationship between the rat liver non-specific lipid-transfer protein (nsLTP) and the 58-kDa protein cross-reactive with anti-nsLTP antibodies, was investigated by cDNA analysis. A 1945-bp cDNA clone was isolated which encodes a 58.7-kDa protein. This protein is identical to the 58-kDa immunoreactive protein determined by N-terminal sequence analysis of the purified 58-kDa protein. It consists of 546 amino acid residues, of which the 123 C-terminal residues are identical to the sequence of nsLTP. The N-terminal 400 amino acid residues of the 58.7-kDa protein were found to have 23.5% identity with the sequence of both mitochondrial and peroxisomal rat 3-oxoacyl-CoA thiolases, including a hypothetical substrate-binding site. The cDNA insert hybridizes with 1.1-kb, 1.7 kb, 2.4-kb and 3.0-kb mRNA species in RNA isolated from various rat tissues and from Chinese hamster ovary (CHO) cells. Southern blot analysis suggests that these mRNA species are generated from a single gene. Mutant CHO cells, deficient in peroxisomes, lack nsLTP. We have found that the mRNA encoding nsLTP is still present in these cells, which suggests that the absence of this protein is related to the lack of peroxisomes. PMID- 1915370 TI - Purification and characterization of a new kappa-carrageenase from a marine Cytophaga-like bacterium. AB - A bacterial strain able to degrade various sulfated galactans (carrageenans and agar) was isolated from the marine red alga Delesseria sanguinea. From the cell free supernatant of cultures grown on crude lambda-carrageenan, a kappa carrageenase was purified by ammonium sulfate fractionation, gel filtration on Sephacryl S 200 HR and ion-exchange chromatography on DEAE--Sepharose-CL6B. The purified kappa-carrageenase was detected as a single protein upon SDS/PAGE. Its molecular mass was estimated at 40 kDa. Activity was observed against kappa carrageenan over the pH range 5.0-8.5 and was optimal at pH 7.2 in Tris buffer or 7.0 in Mops buffer. The enzyme activity remained stable at 30 degrees C, but only for up to 1 h at 40 degrees C. Analysis of the degradation products of the kappa carrageenase by gel filtration and 13C-NMR spectroscopy indicated that the enzyme degrades kappa-carrageenan down to the level of the kappa-neocarratetraose sulfate. The properties of this new enzyme are compared with those of previously characterized carrageenases. PMID- 1915372 TI - Membrane proteins exposed on the external side of the intestinal brush-border membrane have fusogenic properties. AB - The intestinal brush-border membrane contains one or several membrane proteins that mediate fusion and/or aggregation of small unilamellar egg phosphatidylcholine vesicles. The fusion is accompanied by a partial loss of vesicle contents. Proteolytic treatment of the brush-border membrane with proteinase K abolishes the fusogenic property. This finding suggests that the fusogenic activity is associated with a membrane protein exposed on the external or luminal side of the brush-border membrane. Activation of intrinsic proteinases of the brush-border membrane liberates water-soluble proteins (supernate proteins). These proteins behave in an analogous way to intact brush-border membrane vesicles; they induce fusion of egg phosphatidylcholine vesicles and render the egg phosphatidylcholine bilayer permeable to ions and small molecules (Mr less than or equal to 5000). Furthermore, supernate proteins mediate phosphatidylcholine and cholesterol exchange between two populations of small, unilamellar phospholipid vesicles. Supernate proteins are fractionated on Sephadex G-75 SF yielding three protein peaks of apparent Mr greater than or equal to 70,000, Mr = 22,000 and Mr = 11,500. All three protein fractions show similar phosphatidylcholine-exchange activity, but they differ in their effects on the stability of egg phosphatidylcholine vesicles. The protein fraction with an apparent Mr greater than or equal to 70,000 has the highest fusogenic activity while the protein fraction of apparent Mr = 11,500 appears to be most effective in rendering the egg phosphatidylcholine bilayer permeable. PMID- 1915371 TI - N-myristoyl-transferase activity in cancer cells. Solubilization, specificity and enzymatic inhibition of a N-myristoyl transferase from L1210 microsomes. AB - The activity catalyzed by N-myristoyl transferase (NMT) is described for the first time in microsome-rich fractions from the murine leukemia cell line L1210, rat brain and mouse liver as biological sources. The enzyme from each source can accommodate various types of proteins (protein kinase A, virus structural gag protein or pp60src) as modelized by the use of their N-terminal derived peptides (GNAAAARR, GQTVTTPL and GSSKSKPKDP, respectively). As for some other types of membrane-bound enzymes, NMT activity can be enhanced by pretreatment with various types of detergents, amongst which Triton 770 and deoxycholate were the most potent. Further experiments on the L1210 microsome-rich fractions demonstrate that these two detergents were able to solubilize the microsomal enzyme, without modifying its substrate specificity. Finally, three compounds described in the literature to be inhibitors of NMT activity from other sources were tested for L1210 microsome-associated activity. None of them show any significant potency in inhibiting this activity. A new compound, myristoylphenylalanine, shows a slightly better inhibitory effect on the L1210 microsomal activity than the reference compounds with a median inhibitory concentration (IC50) of 0.2 mM. PMID- 1915373 TI - In vivo 31P-NMR studies of Desulfovibrio species. Detection of a novel phosphorus containing compound. AB - The phosphorus metabolism of sulfate-reducing bacteria was, for the first time, probed by in vivo 31P NMR. A novel phosphoric anhydride diester compound was detected in Desulfovibrio desulfuricans ATCC 27774 at intracellular concentrations up to 5 mM. The compound has been extracted and partially purified by anion-exchange chromatography and analysed by 31P, 13C and 1H NMR. These studies show that the novel phosphorus-containing compound is formed by five carbon atoms and is probably cyclic, with a Mr of approximately 300. Various Desulfovibrio strains were examined in vivo for the presence of this phosphorus containing compound. Detectable amounts of the novel metabolite were found in D. desulfuricans ATCC 27774 when grown on lactate/sulfate, lactate/thiosulfate or pyruvate/sulfate. The phosphorus-containing compound was not detected when this strain of D. desulfuricans was grown on lactate/nitrate or pyruvate; neither was it detected in two other strains which, like D. desulfuricans ATCC 27774, have the capability of utilizing nitrate as a terminal electron acceptor. PMID- 1915374 TI - Cloning and expression of human ciliary neurotrophic factor. AB - Ciliary neurotrophic factor (CNTF) is a survival factor for avian ciliary ganglion neurons and a variety of other neuronal cell types in vitro. We report here the cloning of the entire genomic sequence encoding human CNTF and its primary structure. Biologically active CNTF has been expressed in Chinese hamster ovary cells from a human genomic DNA clone. Human CNTF has no significant sequence similarity to any previously reported protein, although approximately 84% similarity exists compared with rat and rabbit CNTF. The lack of both an N terminal signal sequence and consensus sequences for glycosylation or hydrophobic regions, and the fact that active CNTF is expressed but not released into the culture medium of transfected cells, argue in favour of human CNTF as a cytosolic protein. These data provide a basis for understanding the role of CNTF in nervous system physiology and pathology. PMID- 1915375 TI - The influence of transferrin binding to L2C guinea pig leukemic lymphocytes on the endocytosis cycle kinetics of its receptor. AB - The parameters regulating the internalization and recycling of transferrin specific receptors were determined in guinea pig leukemic B lymphocytes, in the absence or presence of ligand. We show that after the cells were purified, 45-56% of the total receptors were on the cell surface. In the absence of transferrin, unoccupied receptors are quickly internalized (rate constant, 0.12 min-1) whereas their recycling is much slower (rate constant, 0.026 min-1). This difference between endocytosis and recycling rates leads to a balanced receptor distribution with only 22% of the total receptors outside after incubation of the cells for 20 30 min at 37 degrees C. The internalization rate of occupied receptors, measured in the presence of transferrin is faster (rate constant, 0.21 min-1) than that of unoccupied receptors calculated in the absence of transferrin (0.12 min-1; see above). On the other hand, mere binding of transferrin to its receptor, without internalization, arrested by cytoplasm acidification, is sufficient to induce a large increase (by a factor of seven) in the recycling rate of unoccupied internal receptors from 0.026 min-1 to 0.17 min-1. Thus, in these lymphocytes, transferrin mobilizes internal receptors by modifying the kinetic rates of internalization and recycling, leading to a new equilibrium between external and internal receptors. PMID- 1915376 TI - The three-dimensional structure of a DNA hairpin in solution two-dimensional NMR studies and structural analysis of d(ATCCTATTTATAGGAT). AB - The hairpin formed by d(ATCCTATTTATAGGAT) was studied by means of two-dimensional NMR spectroscopy and conformational analysis. Almost all 1H resonances of the stem region could be assigned, while the 1H and 31P spectra of the loop region were interpreted completely; this includes the stereospecific assignment of the H5' and H5" resonances. The derivation of the detailed loop structure was carried out in a stepwise fashion including some improved and new methods for structure determination from NMR data. In the first step, the mononucleotide structures were examined. The conformational space available to the mononucleotide was scanned systematically by varying the glycosidic torsion angle and pseudorotational parameters. Each generated conformer was tested against the experimental J coupling constants and NOE parameters. In the following stage, the structures of dinucleotides and longer fragments were derived. Inter-residue distances between protons were calculated by means of a procedure in which the simulated NOEs, obtained via a relaxation-matrix approach, were fitted to the experimental NOEs without the introduction of a molecular model. In addition, the backbone torsion angles beta, gamma and epsilon were deduced from homocoupling and heterocoupling constants. These data served as constraints in the next step, in which the loop sequence was subjected to a multi-conformer generation procedure. The resulting structures were tested against the mentioned constraints and disregarded if these constraints were violated. This yielded a family of structures for the loop region, confined to a relatively narrow conformational space. A representative conformation was subsequently docked on a B-type stem which fulfilled the structural constraints (derived from the NMR experiments for the stem region) to yield the hairpin structure. Results obtained from subsequent restrained-molecular-mechanics as well as free-molecular-mechanics calculations are in accordance with those obtained by means of the analysis described above. The structure of the hairpin loop is a compactly folded conformation and the first base of the central TTTA region forms a Hoogsteen T-A pair with the fourth base. This Hoogsteen base pair is stacked upon the sixth base pair of the B-type double-helical stem. The second base of the loop is folded into the minor groove, whereas the third base of the loop is partly stacked on the first and fourth bases. The phosphate backbone exhibits a sharp turn between the third and fourth nucleotides of the loop. The peculiar structure of this hairpin loop is discussed in relation to loop folding in DNA and RNA hairpins and in relation to a general model for loop folding. PMID- 1915377 TI - Isolation and characterisation of porcine sorbin. AB - Sorbin has been isolated from extracts of porcine upper intestine, and the biological activity in absorbing water and electrolytes utilized to monitor the purification procedure. Pure sorbin was obtained in a yield of about 1 mg/Mg boiled intestine. The protein chain has 153 amino acid residues and the primary structure was determined by analyses of CNBr-cleaved fragments and four enzymatic digests. The protein has a free N-terminal Met and an amidated C-terminal Ala. No structural similarity was observed with other known proteins in data bases, but several segments have special properties and the C-terminal half is rich in Pro and Arg. PMID- 1915378 TI - Human and rodent sequence analogs of Alzheimer's amyloid beta A4 share similar properties and can be solubilized in buffers of pH 7.4. AB - The filamentous amyloid protein aggregates found in the brain of patients affected with Alzheimer's disease principally consist of a peptide termed beta A4, according to its secondary structure of beta-pleated sheets and its molecular mass of about 4 kDa. It has a length of up to 42 or 43 residues. By chemical means, we have synthesized peptide analogs corresponding to the human and rodent beta A4 sequences. We describe structural and functional properties of peptides spanning residues 1-43, 10-23, 1-27 and 4-27 of beta A4. The peptides have been tested for their ability to form filaments in vitro. Their solubilities and secondary structures in solution and in the solid state have been used to detect differences between the properties of human and rodent beta A4 sequences. We show that mouse and rat beta A4 homologs are as amyloidogenic as the human sequence. The absence of amyloid deposits in the brain of aged rats and mice is therefore not due to the three amino acid substitutions identified within the sequence which is homologous to beta A4 of humans. Moreover, peptides corresponding to residues 1-27 of human and rodent beta A4 are solubilized under physiological conditions; thus they are very unlikely to form stable filaments in vivo. PMID- 1915379 TI - Latent fibronectin-degrading serine proteinase activity in N-terminal heparin binding domain of human plasma fibronectin. AB - The N-terminal 70-kDa fragment of human plasma fibronectin, purified from a cathepsin D digest, is characterized by lack of stability. It is processed proteolytically during incubation in the presence of Ca2+ into 27-kDa N-terminal heparin-binding and 45-kDa collagen-binding domains. The N-terminal residue in the 27-kDa fragment was blocked as in native fibronectin. The 45-kDa fragments began with the sequences AAVYQP, AVYQP and VYQP (residues 260, 261, 262-265 of fibronectin) that correspond to the beginning of the collagen-binding domain. In the presence of Ca2+ the purified 27-kDa fragment underwent further processing finally leading to the cleavage of the bond K85-D86 and to the simultaneous appearance of a specific proteolytic activity. Inhibition studies suggests that the newly generated enzyme is a Ca(2+)-dependent serine proteinase. Among all assayed matrix proteins, the newly generated enzyme cleaves native fibronectin and its fragments. It is proposed that this fibronectinase may originate from the N-terminal domain of fibronectin. PMID- 1915380 TI - Transcriptional activation of early-response genes by hydrogen peroxide in a mouse osteoblastic cell line. AB - H2O2, like other oxidants, is known to act as a mitogen at low concentrations in resting Balb/3T3 or mouse epidermal JB6 cells. We described previously that H2O2 induces some early response genes in Balb/3T3 cells. We extended these observations using another cell line, MC3T3 (mouse osteoblastic) cells by examination of transcriptional activity of these genes and by using inhibitors of protein kinases. H2O2 increased the expressions of c-fos, c-jun, egr-1 and JE genes which are known to be early response genes and are induced by mitogenic stimuli in many types of cells. Exogenous addition of H2O2 increased the mRNA levels of these genes, the kinetics of increase being similar to those of their inductions by a phorbol ester or serum. Nuclear run-on transcription showed that this induction occurred at the transcriptional level. H2O2 at 0.1-0.2 mM induced maximal expressions of c-fos and c-jun, whereas 0.3 mM H2O2 was required for induction of stress-induced heme oxygenase mRNA. The inductions of c-fos and c jun were inhibited by 50 microM H7, a protein kinase inhibitor that is relatively specific for protein kinase C, but were not affected by H9, relatively specific for cAMP-dependent protein kinase. In cells pretreated with 12-O tetradecanoylphorbol 13-acetate, however, in which protein kinase was supposed to be downregulated, H2O2 induced c-fos and heme oxygenase as efficiently as in untreated cells. H2O2 did not increase the phosphorylation of p80 protein, which is known to be a substrate for protein kinase C. Thus, H2O2 seemed to induce c fos and c-jun by activating protein kinases distinct from protein kinase C. Activity of the chloramphenicol acetyltransferase gene under control of the serum response element of human c-fos genes was increased by H2O2 treatment, whereas that under control of cAMP-response element was not affected. These results indicate that the inductions by H2O2 of c-fos and possibly other early response genes are mediated through activation of the serum-response element in their enhancer. PMID- 1915381 TI - Selective decontamination of the intestines: an important clinical treatment modality? PMID- 1915382 TI - Review of Citrobacter bacteremia in cancer patients over a sixteen-year period. AB - A review was conducted of 65 episodes of Citrobacter bacteremia in cancer patients during a 16-year period. Cases of polymicrobial bacteremia were excluded from this analysis. The infection occurred most commonly in patients with acute leukemia. Most patients acquired the infection in the hospital, and 57% had received antibiotic therapy during the preceding ten days. Fever occurred in 98% of cases and shock in 17%. Thirty-eight percent of patients had concomitant pneumonia. Patients with shock, pneumonia or hemorrhage had a substantially poorer prognosis. The response rate was 72% for patients who received appropriate antibiotics. Patients who continued to have positive blood culture results while receiving appropriate antibiotic therapy had a poor prognosis. Beta-lactam antibiotics were more effective than aminoglycosides. PMID- 1915384 TI - In vitro phagocytic interaction between Trichomonas vaginalis isolates and bacteria. AB - The phagocytic activity of 12 Trichomonas vaginalis isolates against both gram positive bacteria (Staphylococcus aureus ATCC 25923, Lactobacillus spp.) and gram negative bacteria (Enterobacter cloacae ATCC 13047, 5 strains of Escherichia coli, Pseudomonas aeruginosa ATCC 27853) was studied. Results showed that all the isolates were able to ingest Staphylococcus aureus to a variable degree, and almost all of them showed phagocytic activity against Pseudomonas aeruginosa. Furthermore, experiments with a restricted number of isolates of Trichomonas vaginalis showed that they phagocytized, often very effectively, human vaginal lactobacilli. Only in some cases was the addition of serum essential for bacteria ingestion. Phagocytic uptake of Escherichia coli and Enterobacter cloacae was not detectable under the experimental conditions used. It is concluded that phagocytosis may be involved in changes in vaginal biocenosis during the early stages of trichomoniasis. PMID- 1915383 TI - Non-typhoid Salmonella bacteraemia in Greater Copenhagen 1984 to 1988. AB - A retrospective survey of non-typhoid Salmonella bacteraemia in the period 1984 to 1988 was carried out by the five departments of clinical microbiology in Greater Copenhagen. A total of 168 patients were identified. A gradual increase was observed from 11 cases in 1984 to 58 cases in 1988. The corresponding incidence per 100,000 inhabitants in Copenhagen rose from 0.9 in 1984 to 5.0 in 1988. During the same period the total registered incidence of human Salmonella infections in Denmark increased from 17.6 to 67.4 per 100,000 inhabitants. The serotype most often isolated from bacteraemic patients was Salmonella dublin followed by Salmonella enteritidis and Salmonella typhimurium. Salmonella dublin demonstrated enhanced invasive and pathogenic properties. Predisposing factors were present in 56% of the patients; the most common was malignant disease. A fatal or complicated course of the bacteraemia was observed more frequently in patients with underlying diseases than in persons who had previously been healthy. A total of 17% of the patients died; one-fifth of these had a ruptured aortic aneurysm. It is concluded that the substantial increase in the number of cases and the often serious course taken by the infection demonstrate a need for increased efforts at prophylaxis. PMID- 1915385 TI - Efficacy of oral fluconazole in the treatment of AIDS associated oesophageal candidiasis. AB - To assess the efficacy and tolerance of fluconazole in the treatment of oesophageal candidiasis, 47 AIDS patients with this infection were enrolled in an open prospective study using fluconazole 100 mg given orally once daily. Clinical cure was obtained in all of 41 evaluable patients, with confirmation of cure in all of 31 patients who underwent post-treatment oesophagoscopy. Forty patients were followed up for at least 30 days; none suffered a relapse of oesophagitis but seven had a recurrence of stomatitis which was effectively treated with fluconazole. Fluconazole was well tolerated. Nausea was noted in three patients one of whom interrupted therapy. Transient mild elevation of ALT/AST was noted in five of 41 patients (12%). Fluconazole appears to be a safe and effective agent for oral therapy of oesophageal candidiasis associated with AIDS. PMID- 1915386 TI - Leuconostoc species as a cause of bacteremia: two case reports and a literature review. AB - Two new cases of significant bacteremia caused by Leuconostoc spp. are reported and five others described in the literature are reviewed. Four of the seven patients were under one year old and presented with prolonged diarrhea related to gastrointestinal disorders. The remaining three patients were over 50 years of age and being treated in intensive care units. Six patients had nosocomially acquired catheter-related bacteremia. Leuconostoc spp. are naturally resistant to vancomycin, and five patients had received this antibiotic for prior bacteremia caused by methicillin-resistant staphylococci. The majority of patients presented with fever without severe complications. Penicillin is the treatment of choice and there is no report of any death directly attributable to infection by these microorganisms. Infection with Leuconostoc spp. should be suspected if "vancomycin-resistant streptococci" are isolated from the blood, and recorded as a potential cause of bacteremia in patients with indwelling intravenous catheters. PMID- 1915387 TI - Peritonitis with CDC group IVc-2 bacteria in a patient on continuous ambulatory peritoneal dialysis. AB - A case of CDC group IVc-2 peritonitis in a patient on continuous ambulatory peritoneal dialysis (CAPD) is described. To the authors' knowledge, this is the first case reported of CAPD peritonitis in which a member of this unusual group of bacteria was isolated as the sole microorganism. As this microorganism is usually resistant to most antibiotics commonly used to treat peritonitis in patients on CAPD, microbiological investigations with identification and antimicrobial susceptibility tests are mandatory. PMID- 1915388 TI - Penetration of ciprofloxacin into human cerebrospinal fluid in patients with inflamed and non-inflamed meninges. AB - The penetration of ciprofloxacin into the cerebrospinal fluid (CSF) in 25 patients with non-inflamed meninges and in 9 patients with inflamed meninges was studied. In the patients with non-inflamed meninges plasma and CSF were obtained 1-10 h after the second dose of ciprofloxacin and in the patients with inflamed meninges 1, 2, 3, 5, 7 and 9 h after the second dose. In the first group (non inflamed meninges) data from 6 patients were obtained 4, 5 and 6 h post-dose. Mean ciprofloxacin concentrations in the CSF ranged from 0.073 mg/l to 0.106 mg/l during this observation time, while in the second group (inflamed meninges) they ranged from 0.089 to 0.260 mg/l. These results demonstrate that ciprofloxacin diffuses into the CSF at concentrations which exceed the MICs of Neisseria meningitidis and most gram-negative aerobic bacilli. PMID- 1915389 TI - Sensitivity of Helicobacter pylori to different bile salts. AB - The sensitivity of Helicobacter pylori to different unconjugated or conjugated bile acids both on BHI blood agar and in BHI broth supplemented with starch, horse serum or egg yolk was studied. Bile salts were more toxic in the medium containing starch than in the media containing horse serum or egg yolk, and unconjugated bile salts were more toxic than the conjugated salts. Deoxycholic acid was the most toxic of the bile acids studied. Ox bile was bacteriostatic at the 2% level. Bile Salts 3 mixture was bactericidal at a concentration of 0.25 mmol. PMID- 1915390 TI - Effect of meropenem on the intestinal microflora. AB - Ten healthy volunteers were given 500 mg of meropenem by intravenous infusion over 30 min three times daily for seven days. Stool specimens were collected before, during and after meropenem administration. The numbers of enterobacteria and streptococci decreased during the administration period, while the numbers of enterococci increased. There was a decrease in the numbers of clostridia, bacteroides and gram-negative cocci, while the numbers of gram-positive cocci and rods were not changed by the administration of meropenem. The intestinal flora returned to normal in all volunteers within two weeks after the termination of meropenem administration. PMID- 1915391 TI - Endocarditis caused by an unidentified gram-positive coccus. PMID- 1915392 TI - Sacro-iliac joint infection caused by Eikenella corrodens. PMID- 1915393 TI - Isolation of a dysgonic fermenter (DF-3) from urine of a patient. PMID- 1915394 TI - Improved tween 80 hydrolysis method for identification of Moraxella (Branhamella) catarrhalis. PMID- 1915395 TI - Possibility of heterosexual transmission of hepatitis C virus. PMID- 1915396 TI - Enzyme immunoassay for detection of immunoglobulin M antibodies to Giardia lamblia. PMID- 1915398 TI - Latex agglutination for rapid identification of methicillin-resistant Staphylococcus aureus recovered from selective media. AB - The accuracy of combining latex agglutination with selective media for the identification of methicillin-resistant Staphylococcus aureus (MRSA) was determined. Test strains were identified by latex agglutination on blood agar, the heat-stable thermonuclease test and broth microdilution MICs of oxacillin and included 97 MRSA, 56 methicillin-susceptible Staphylococcus aureus, 52 methicillin resistant, and 49 methicillin-susceptible Staphylococcus species. Isolates were grown on trypticase-soy agar with 5% sheep red blood cells (TSAB), Mueller-Hinton agar (MHA), mannitol-salt agar (MSA), and four media designed for the selective growth of MRSA:TSAB with clindamycin and gentamicin, MHA with oxacillin, MSA with oxacillin, and lipovitellin-salt-mannitol agar (LVSM) with 1 microgram oxacillin disks applied. The mean sensitivity, specificity, and positive predictive value for the combination of latex agglutination with selective media for the identification of MRSA was 96%, 99% and 98% respectively. PMID- 1915399 TI - Effect of washing sputum on detection of pneumococcal capsular antigen. AB - The effect of washing of sputum on detection of pneumococcal capsular antigen was investigated. A total of 357 sputa from 104 patients was tested. Antigen could be detected in 164 (46%) of the sputa in both the washed and unwashed portions, and could not be detected in either portion in a further 180 (50%) sputa. Four (1%) of the sputa agglutinated in the negative control, and were considered to be auto agglutinating. In 9 (3%) sputa antigen could be detected in the unwashed portion, but not in the washed portion. There were no specimens in which antigen could be detected in the washed portion only. These data indicate that pneumococcal capsular antigen can be detected as reliably in washed sputum as in unwashed sputum. PMID- 1915397 TI - Comparison of two schedules of cefoperazone plus aztreonam in the treatment of neutropenic patients with fever. AB - Cancer patients were randomized to receive an every 4 hour or every 8 hour schedule of cefoperazone plus aztreonam during 617 febrile episodes. The overall response rate for the 478 evaluable episodes was 76% and there was no difference in response rate between the two schedules. The response rate was 79% for cases of pneumonia and 63% for cases of bacteremia. Only 50% of the microbiologically documented infections caused by gram-positive organisms responded whereas 95% of gram-negative infections, including all of those caused by Pseudomonas aeruginosa, responded. Response rates were lower among patients whose neutrophil counts decreased during therapy than among those whose neutrophil counts increased (64% vs. 85%, p = 0.008). Side-effects that were possibly or probably related to antibiotic therapy were observed during 11% of the episodes. The most common side-effects were diarrhea and rashes including one case of Stevens Johnson syndrome. Three patients developed a coagulopathy during therapy. Cefoperazone plus aztreonam proved to be an effective combination for treatment of gram-negative infections and fever of unknown origin in cancer patients and an every 8-hour schedule of administration was as effective as an every 4-hour schedule. Approximately half of the patients with gram-positive infections required additional antibiotics for successful therapy. PMID- 1915400 TI - In vitro activity of cefpodoxime, a new oral cephalosporin, compared with that of nine other antimicrobial agents. AB - The in vitro activity of the compound RU-51746, the sodium salt of cefpodoxime (which is administered orally as the ester cefpodoxime proxetil) was compared with that of other commonly used oral antibiotics against a selection of clinical isolates of common bacteria from patients with urinary tract, soft tissue and respiratory tract infections. RU-51746 was found to inhibit 90% of Enterobacteriaceae at less than 1 mg/l; pneumococci, pyogenic streptococci (Lancefield groups A, C and G) and Streptococcus agalactiae were almost all inhibited by concentrations of less than 0.06 mg/l; Haemophilus influenzae (including beta-lactamase producers) were inhibited by less than 1 mg/l; 90% of Branhamella catarrhalis were inhibited at less than 2 mg/l. Activity against Acinetobacter spp. and staphylococci was variable and enterococci were all resistant. PMID- 1915402 TI - In vitro activity of cefpodoxime against staphylococci in comparison to other cephalosporins. PMID- 1915401 TI - In vitro activity of cefpodoxime against bacterial isolates obtained from patients with cancer. AB - The in vitro activity of cefpodoxime, an oral cephalosporin ester, against 792 bacterial isolates representing 36 species was evaluated in comparison to that of ciprofloxacin and trimethoprim/sulfamethoxazole (TMP/SMX). Cefpodoxime inhibited the majority of Streptococcus spp., Haemophilus influenzae and Proteus mirabilis at a concentration of less than or equal to 0.12 microgram/ml. It was also active against Citrobacter diversus, Escherichia coli, Klebsiella spp., Proteus vulgaris, Serratia marcescens and methicillin-susceptible Staphylococcus aureus isolates. Overall, cefpodoxime appeared to be less active than ciprofloxacin and TMP/SMX against many pathogens common in cancer patients. PMID- 1915403 TI - Isolation of Bacteroides ureolyticus from the female genital tract. PMID- 1915404 TI - Flavimonas oryzihabitans as a cause of ocular infection. PMID- 1915407 TI - In vitro antimicrobial properties of deferoxamine mesylate. PMID- 1915406 TI - False resistance results using 5 micrograms cefixime disks to test Haemophilus influenzae. PMID- 1915405 TI - Lack of evidence of an etiological role of Chlamydia trachomatis in recurrent otitis media. PMID- 1915408 TI - Emergence of Candida krusei infections after therapy of oropharyngeal candidiasis with fluconazole. PMID- 1915409 TI - Prosomes (proteasomes) of higher plants. AB - From different plant tissues such as tobacco (Nicotiana rustica), potato (Solanum tuberosum), and mung bean (Phaseolus radiatus), ring- or cylinder-shaped particles called prosomes were isolated by either sucrose gradient centrifugation or fast protein liquid chromatography (FPLC). These particles have a diameter of 12 to 14 nm and a length of 16 to 18 nm. They migrate under conditions of nondenaturing gel electrophoresis as one distinct band. Sedimentation coefficient and buoyant density in Cs2SO4 of the plant prosomes were determined by analytical ultracentrifugation to be approximately 23S and 1.23 g/cm3, respectively. The total molecular mass was estimated by gel filtration to be 650 kDa. Plant prosomes are composed of 12 to 15 proteins with molecular masses in the range of 24 to 35 kDa with isoelectric points of pH 5 to 7 as revealed by two-dimensional gel electrophoresis. The protein patterns of prosomes from the three different plant species are very similar. Polyclonal antisera against potato prosomes reacted in Western blots with prosomal proteins of all three plant species. They also bind to some prosomal proteins of animal species. Antisera against animal prosomes react with some proteins of plant prosomes. As shown by lectin blotting, plant prosomes are glycosylated carrying glucosyl- or mannosyl, and N acetylgalactosaminyl residues. Prosomal preparations contain non-stoichiometric amounts of small RNA of about 80 kDa. These results suggest that plant prosomes are structurally and functionally homologous to prosomes of other eukaryotic cells. PMID- 1915410 TI - UV-microbeam irradiations of the mitotic spindle: spindle forces and structural analysis of lesions. AB - Mitotic PtK1 spindles were UV irradiated (285 nm) during metaphase and anaphase between the chromosomes and the pole. The irradiation, a rectangle measuring 1.4 x 5 microns parallel to the metaphase plate, severed between 90 and 100% of spindle microtubules (MTs) in the irradiated region. Changes in organization of MTs in the irradiated region were analyzed by EM serial section analysis coupled with 3-D computer reconstruction. Metaphase cells irradiated 2 to 4 microns below the spindle pole (imaged by polarization optics) lost birefringence in the irradiated region. Peripheral spindle fibers, previously curved to focus on the pole, immediately splayed outwards when severed. We demonstrate via serial section analysis that following irradiation the lesion was devoid of MTs. Within 30 s to 1 min, recovery in live cells commenced as the severed spindle pole moved toward the metaphase plate closing the lesion. This movement was concomitant with the recovery of spindle birefringence and some of the severed fibers becoming refocused at the pole. Ultrastructurally we confirmed that this movement coincided with bridging of the lesion by MTs presumably growing from the pole. The non-irradiated half spindle also lost some birefringence and shortened until it resembled the recovered half spindle. Anaphase cells similarly irradiated did not show recovery of birefringence, and the pole remained disconnected from the remaining mitotic apparatus. Reconstructions of spindle structure confirmed that there were no MTs in the lesion which bridged the severed spindle pole with the remaining mitotic apparatus. These results suggest the existence of chromosome-to pole spindle forces are dependent upon the existence of a MT continuum, and to a lesser extent to the loss of MT initiation capacity of the centrosome at the metaphase/anaphase transition. PMID- 1915411 TI - Gastric lipase and pepsinogen during the ontogenesis of rabbit gastric glands. AB - In rabbit stomach, gastric lipase activity level was found to increase from birth to 30 days old (weaning), and then decreased. In contrast, pepsin activity only appeared between 30 to 45 days old, and increased till to the adult level. It was observed that maturation of gastric glands in cardial mucosa was a downward elongation process from the mitotic cell pool. These mitotic cells were always found in the neck of the gastric glands, corresponding to the bottom of the gland at 6 days old and to the mid-zone of the gland in adult. Location of rabbit gastric lipase (RGL) cells in cardial glands varied with age and was found along the pit of the gastric glands at 6 days old. The extent of this cellular location decreased with age, whereas a second RGL cell zone appeared below the mitotic cell area at 18 and 30 days old. At 45 days old, the pepsinogen cells appeared in the bottom of the gland, and consequently the RGL cells were located in the mid zone of the gastric glands, between mitotic cells (neck of the gland) and pepsinogen cells (lower part of the gland). Ultrastructural study of cardial gastric glands revealed different morphologies of the secretion granules in the cells along the gastric glands. In 6-day-old rabbits, secretory granules were found uniformly electron dense in the bottom of the glands and were RGL-labeled by the immunogold technique. In the medium part of the glands, granules appeared biphasic, with a clear and a dense part, and RGL labeling was confined to the electron-dense part.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915412 TI - Acinar heterogeneity of the epidermal growth factor receptor in the liver of male rats. AB - Epidermal growth factor is cleared from the circulation by the liver, forming a very steep portal-to-central sequestration gradient. It was unknown whether this was due to the position within the liver acinus or whether it was due to functional differences in the hepatocytes. Experiments were undertaken to elucidate the lobular distribution and heterogeneity of the epidermal growth factor receptor in rat liver. Immunocytochemistry showed a predominantly higher staining density over periportal localized hepatocytes. Receptor binding studies with isolated, cultured hepatocytes, enriched in periportal or perivenous located cells, were performed. Our data revealed high- and low-affinity binding sites with a kd of 26 pM and 0.87 nM, respectively, for periportal hepatocytes. The high-affinity receptors were restricted to the periportal hepatocytes only, whereas the number of low-affinity receptors showed a 3 to 4-fold concentration gradient between both cell populations. PMID- 1915413 TI - Biosynthesis and processing of polysialylated NCAM by AtT-20 cells. AB - Polysialylation is a unique posttranslational modification of NCAM. In this report, we investigated the kinetics and localization of NCAM polysialylation in AtT-20 cells. We show that this cell line expresses both the 180 kDa and 140 kDa isoforms of NCAM, in agreement with the proposal that it belongs to a neuroendocrine lineage. The two NCAM chains bear polysialic acid (PSA) and migrate in sodium dodecyl sulfate (SDS) gels as a diffuse, high Mr component, as has been observed in fetal brain. Polysialylation of neosynthesized NCAM was found to be a rapid event, occurring within 8 to 13 min after the beginning of the pulse and appeared to be essentially complete as soon as it was detected. Treatment with endosialidase specific for PSA led to the appearance of two components of 200 and 160 kDa which still bear short sialosyl oligomers. Neither this treatment nor the slowing down of synthesis by lowering the temperature revealed any intermediate bearing oligomers of polysialic acid in the process of elongation suggesting the possibility that polysialylation may involve the transfer to NCAM of preassembled completed PSA chains. Endo H resistance preceded polysialylation, which was totally blocked by monensin and swainsonine which inhibit transport of plasma membrane or secreted proteins within the Golgi complex and the maturation of complex-type oligosaccharide chains, respectively. Depletion of cell-surface NCAM with proteinase K did not prevent the appearance of polysialylated molecules in similar amounts as in untreated cells suggesting that NCAM polysialylation occurs either in a late Golgi or in a post-Golgi compartment but before the molecules reach the plasma membrane. PMID- 1915414 TI - Human nucleoporin p62 and the essential yeast nuclear pore protein NSP1 show sequence homology and a similar domain organization. AB - NSP1 is an essential nuclear pore protein in yeast. We observed that anti-NSP1 antibodies label mammalian nuclear pore complexes and recognize nucleoporin p62. Also peptide antibodies raised against the NSP1 carboxy-terminal end cross-react with p62, a conserved component of the nuclear pore complex in higher eukaryotes. To further analyze the structural and functional similarity between NSP1 and mammalian nucleoporins, we cloned and sequenced nucleoporin p62 from a HeLa cDNA library. Human p62 consists of a carboxy-terminal domain homologous to the essential yeast NSP1 carboxy-terminal domain and an amino-terminal half resembling the repetitive middle domain of NSP1. The full-length p62 and a fusion protein consisting of cytosolic mouse dihydrofolate reductase (DHFR) and the p62 carboxy-terminal domain were expressed in transfected HeLa cells. Only overexpressed full-length p62, but not the DHFR-C-p62 fusion protein, binds wheat germ agglutinin (WGA). This suggests that modification by N-acetylglucosamine is mainly restricted to the repetitive amino-terminal half of p62 and implies a role of this type of repetitive sequences in nuclear transport. In the transfected HeLa cells, the DHFR-C-p62 fusion protein forms patchy aggregates that accumulate at the nuclear periphery but are also scattered through the cytoplasm. It is suggested that nucleoporin p62 may be targeted and anchored to the pore complex via its carboxy-terminal domain which reveals a hydrophobic heptad repeat organization similar to that found in lamins and other intermediate filament proteins. PMID- 1915415 TI - Detection of an elicitor on infection structures of Puccinia graminis using monoclonal antibodies. AB - The basidiomycetous fungus Puccinia graminis f. sp. tritici causes the stem rust disease of wheat. Resistance of wheat to the fungus is often associated with the hypersensitive reaction of infected host cells. A glycoprotein isolated from germ tube cell walls of the pathogen elicits a hypersensitive-like response when injected into wheat leaves. Infection structures morphologically identical to those grown on wheat were induced in the absence of the host plant, and indirect immunofluorescence together with specific monoclonal antibodies to the elicitor was employed to locate the antigen at fungal infection structures. No binding occurred to germ tubes or appressoria. The antibodies located the antigen only at that part of the fungal infection structure that develops endophytically in nature and, moreover, only at the youngest part of this structure. In rust infected wheat leaves, the immunolabel appeared only at haustoria, the structures thought to be involved in specific recognition between host and parasite. PMID- 1915416 TI - Phosphorylation of ribosomal protein S10 is dispensable for initiation of DNA replication and bud emergence in Saccharomyces cerevisiae. PMID- 1915417 TI - Cell cycle-dependent ADP-ribosylation of the nuclear matrix. PMID- 1915418 TI - Differentiation-specific gene expression from the H10 histone promoter in ES cells. PMID- 1915419 TI - Nuclear pore complex glycoprotein p62 of Xenopus laevis and mouse: cDNA cloning and identification of its glycosylated region. AB - cDNA clones for nuclear pore complex glycoprotein p62 of two distantly related species, mouse and Xenopus laevis, were isolated. Antibodies raised against recombinant murine p62 react on protein blots with p62 of both species and decorate pore complexes. Analysis of the predicted protein sequence indicates that vertebrate p62 is organized into two structurally different regions. The entire carboxy-terminal half (86.7% identical amino acids) and the amino-terminal 56 amino acids (62.5% identity) have been highly conserved during evolution. The amino-terminal half contains several penta amino acid repeats and is able to form beta-sheets, whereas the carboxy-terminal half is predominantly organized in alpha-helical structures in part with heptad repeats typical for intermediate filament proteins. p62 of mouse and Xenopus is glycosylated by N acetylglucosamine additions in the amino-terminal half. The region containing these potential glycosylation sites has been identified. PMID- 1915420 TI - Endocytosis of human IgG:Fc receptor complexes by transfected BHK cells. AB - We have analyzed the mode of uptake of human beta FcRII molecules expressed in BHK cells (clone 2/14). When challenged with aggregated human IgG (ahIgG), these cells bind the ligand at 4 degrees C and endocytose the IgG: receptor complexes rapidly upon warming to 37 degrees C, as seen by fluorescence microscopy with antibodies directed against human IgG. Using 125I-labeled ahIgG, we found that 40% of the bound ligand was internalized within 15 min, and approximately 60% within 2 h. Surface replication and thin sectioning combined with immunogold labeling revealed that the ligand was taken up by coated vesicles and was transferred to the endosomal/lysosomal compartment. This was confirmed by confocal laser microscopy of cells double labeled for clathrin and ahIgG. After modulation of the coated vesicle pattern by hypertonic medium, ahIgG transport was impaired. These data show that a single isoform of human FcRII, expressed in an animal cell negative for Fc receptors, can use the coated vesicle based endocytic pathway of the host cell. Reincubation of cycloheximide-treated cells with a second batch of ligand showed that approximately 20% of the beta FcRII was recycled. This finding is in apparent contrast to the fate of the endogenous Fc receptors expressed on mouse macrophages. PMID- 1915421 TI - Temperature dependence of prolactin endocytosis and casein exocytosis in epithelial mammary cells. AB - As previously reported in epithelial mammary cells of lactating rabbit, prolactin exerts a stimulatory effect on casein secretion. After binding to a membrane receptor, the complex hormone-receptor is internalized in mammary cells. Peptide hormone action involves the generation of second messengers. These second messengers can be emitted as soon as hormone is linked to the membrane receptor. However, it is not excluded that endocytosis and transfer of prolactin inside the cell take part in the emission of second messenger and related secretory response. In order to precise intracellular transport pathways in the lactating mammary cell, we have examined the effects of reduced temperature on the one hand on prolactin endocytosis, on the other hand on casein secretion and on the stimulating effect of prolactin on casein secretion. Endocytosed prolactin was cytochemically localized mainly on the plasma membrane at 4 degrees C. At 25 degrees C, the hormone accumulated, during 60 min, in endosomes and multivesicular bodies. At 37 degrees C, prolactin was detectable after 15 and 30 min inside the cells and disappeared after 60 min. Transport and exocytosis of secretory proteins were only partly inhibited at 25 degrees C as attested by autoradiography localization and biochemical assays of newly synthesized caseins. However, at 25 degrees C, prolactin was no more able to stimulate casein exocytosis. These results show that intracellular transport of prolactin and secretagogue effect of the hormone does not proceed at 25 degrees C. However, secretory mechanisms of the cell are always able to be stimulated by exogenous arachidonic acid at this temperature. Low temperature appears as a good means to study intracellular transport in the mammary cell. PMID- 1915422 TI - Catheter ablation of left posteroseptal accessory pathways and of long RP' tachycardias with a right endocardial approach. AB - Fifty-four patients with a posteroseptal accessory connection and symptomatic tachycardias underwent catheter ablation of the anomalous pathway. Eight had the permanent form of reciprocating tachycardias (long RP' tachycardia) and 46 had a left posteroseptal preexcitation marked by a prominent R wave in lead VI. In 14 of 19 patients, ventriculoatrial conduction time during tachycardia lengthened in conjunction with functional left bundle branch block; this behaviour was significantly different from a series of patients with right posteroseptal preexcitation in which functional left bundle branch block lengthened the ventriculoatrial time in only one of 12 patients. A quadripolar electrode catheter was left within the proximal coronary sinus in order to locate the earliest atrial or ventricular activation site. The appropriate bipole was used as the radiographic and electrophysiological reference of the insertion of the accessory pathway. A catheter was then positioned on the septal side of the right atrium, outside the coronary sinus, so that atrial activity during reciprocating tachycardia and ventricular activity during preexcitation were synchronous with or earlier than that recorded within the proximal coronary sinus. Accessory pathway potential was not recorded in any patient. Early ventricular potential occurring --1.5 +/- 8 ms relative to delta wave onset was present at that site. In 38 patients, including 5 with permanent junctional tachycardia, high current (14 mA) pacing yielded direct ventricular paced QRS complexes (no delay spike QRS) with a morphology similar to left posteroseptal maximal preexcitation. Slight movements of catheter position yielded significantly different pace-maps. One to eight 160 J cathodal shocks (510 +/- 213 J cumulative per patient) were delivered at this site in 61 sessions. Following fulguration, tachycardia recurred without drugs in only one patient over a follow-up period of 20 +/- 13 months. Asymptomatic intermittent preexcitation recurred in two patients. In all patients with long RP' tachycardia, the ablation procedure was successful without the need for drugs or permanent cardiac pacing. A long-term follow-up electrophysiological study in 18 patients demonstrated that conduction through the anomalous pathway was absent in 16 and deeply altered in the two patients with intermittent preexcitation; no tachycardia was inducible in any patient. In conclusion, catheter ablation of left posteroseptal accessory pathways is a feasible procedure using a right atrial approach outside the coronary sinus. This technique is also effective for the treatment of the permanent form of reciprocating tachycardia. PMID- 1915423 TI - Peak aortic blood acceleration: a possible indicator of initial left ventricular impairment in patients with coronary artery disease. AB - In 25 patients undergoing diagnostic cardiac catheterization, a catheter-tip electromagnetic velocity transducer was used to evaluate maximum velocity and acceleration of blood in the ascending aorta. All patients underwent a complete haemodynamic evaluation, including high-fidelity recording of intraventricular pressures and calculation of the derived indices, left ventriculography and coronary angiography. Nineteen patients with critical coronary stenoses were divided according to the presence of signs of left ventricular dysfunction, while the control group consisted of six subjects with chest pain, but without cardiac abnormalities detectable by cardiac catheterization. Maximum aortic acceleration was significantly lower in coronary patients (378 +/- 130 vs 562 +/- 82 in the control group P less than 0.01) and also in the selected subgroup of coronary patients with normal haemodynamic and angiographic indices of left ventricular systolic function (310 +/- 102 vs 562 +/- 82, P less than 0.01). No relationship could be observed between maximal blood acceleration and left ventricular peak systolic pressure, +dP/dt, left ventricular end-systolic volume index and ejection fraction. Our results suggest that maximal blood acceleration from the left ventricle may detect an initial myocardial impairment in patients with definite coronary artery disease but with normal conventional indices of left ventricular function. The clinical interest of this index, however, is limited by overlapping values in patients with and without coronary artery disease and the inability of a further separation of ischaemic patients in accordance with the severity of left ventricular impairment and the extension of coronary artery involvement. PMID- 1915424 TI - The relationship between coffee consumption and lipid levels in young and older people in the Heidelberg-Michelstadt-Berlin study. AB - The relationship between coffee consumption and serum lipid levels was studied in a randomly selected sample of 395 young and 385 elderly adults in the Federal Republic of Germany. Analyses were done separately for men and women and for young and older people. After adjustment for body mass index, activity level, smoking, total energy intake, dietary fat, fish, milk, tea and alcohol consumption and oral contraceptive use a statistically significant increase in total serum- and LDL-cholesterol levels with increased coffee consumption was observed in the group of young men only. In this subgroup a difference of 0.11 mmol.l-1 serum cholesterol and of 0.10 mmol.l-1 LDL cholesterol for each additional cup of coffee consumed daily was calculated. This is one of the few studies that includes elderly people. No significant trend was seen between coffee consumption and serum- or LDL-cholesterol levels in the elderly. PMID- 1915425 TI - Degenerative aortic regurgitation. AB - In view of the growing incidence of degenerative origin among the aetiologies of aortic regurgitation, we felt it interesting to report our experience of the surgical treatment of such patients. Out of 313 patients operated on for isolated chronic aortic regurgitation between 1974 and 1989, 102 (32.6%) had aortic regurgitation of degenerative origin and form the basis of this study. The patients were divided into group I (n = 48) without aneurysm of the ascending aorta and group II (54 patients) with anulo-aortic ectasia. The first group was further subdivided according to the diameter of the ascending aorta: in group Ia (23 patients) the aorta was normal with a root diameter of less than 40 mm, while in group Ib (25 patients) the aorta was enlarged (root diameter between 40 and 54 mm). There was no statistically significant difference between the pre-operative and operative parameters of patients in groups Ia and Ib. All underwent aortic valve replacement without associated surgery of the ascending aorta. During a mean follow-up of 58 months, five patients from group Ib had aortic dissection and in another three, an ascending aorta aneurysm developed. Reoperation was performed in six cases. No such complications occurred in group Ia. At 6 years, the proportion of patients free from complications related to the ascending aorta was 100% in group Ia vs 63 +/- 6% in group Ib (P less than 0.05). In group II, all the patients underwent aortic valve replacement. The modalities of repair of the ascending aorta differed with time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915426 TI - The relationship between causal attribution and rehabilitation in patients after their first myocardial infarction. A cross cultural study. AB - Full rehabilitation of a patient following myocardial infarction (MI) involves resumption of work and the restoration of quality of life. Two groups of patients (87 Israeli and 98 Swedish) were admitted to the CCU and followed up after their first MI. To evaluate the patients' own perception of events ('causal attribution theory'), sequential interviews were scheduled. Physical risk factors correlated poorly with rehabilitation outcome at 6 months. However, two patient clusters were pinpointed according to the patients' subjective explanation of the factors contributing to their MI. These 'causal attribution scores' had a predictive value, independent of culture, age, education, disease severity and depression. It is therefore concluded that evaluation of patient perception may assist in planning intervention for high risk psychologically debilitated patients, and thus favourably enhance their rehabilitation outcome. PMID- 1915427 TI - Comparison of hormonal and haemodynamic changes after long-term oral therapy with pimobendan or enalapril--a double-blind randomized study. AB - Twenty-four patients (one female, 23 male) with mild to moderate heart failure were randomly and double-blindly assigned to an oral treatment with 5 mg enalapril twice daily or 5 mg pimobendan (UDCG 115) twice daily. After the first tablet intake, blood pressure and heart rate were measured for 6 h. Therapy continued over 6 months. Systolic arterial blood pressure dropped from 126 +/- 20 mmHg to 111 +/- 14 mmHg (P less than 0.05) after the first enalapril tablet and from 123 +/- 16 mmHg to 112 +/- 13 mmHg (P less than 0.05) after the first pimobendan tablet. After 6 months, no important changes in blood pressure were observed in the pimobendan group and only a minor decrease in the enalapril group. There was no significant change in heart rate either after the first dose or after long-term therapy with either medication. After 6 months, cardiac index increased from 2.73 +/- 0.75 l.min-1.m-2 to 3.38 +/- 0.69 l.min-1.m-2 (P less than 0.01) after pimobendam, but did not change after enalapril (2.95 +/- 0.75 l.min-1.m-2 to 2.96 +/- 0.89 l.min-1.m-2, NS). Pulmonary capillary wedge pressure decreased during pimobendan long-term therapy from 16 +/- 8 mmHg to 14 +/- 8 mmHg (NS) and during enalapril from 21 +/- 7 to 14 +/- 7 mmHg (P less than 0.01). Exercise capacity increased in the pimobendan group from 17.2 +/- 5.4 kJ to 23.0 +/- 9.6 kJ (P less than 0.05), and in the enalapril group from 20.4 +/- 11.9 kJ to 24.8 +/- 18.5 kJ (NS) during long-term therapy over 6 months. Plasma renin activity increased from 0.96 to 3.6 ng.ml-1.h-1 (P less than 0.05) during enalapril long-term therapy, but remained unchanged (1.38 vs. 1.32 ng.ml-1.h-1, NS) during pimobendan. The new inotrope, pimobendan, exerted favourable long-term effects without haemodynamic or humoral signs of tolerance development. PMID- 1915429 TI - Significance of ST segment changes induced by dobutamine stress test after acute myocardial infarction. Which are reciprocal? AB - In order to determine the significance of predischarge stress-induced ST segment changes after a first non-complicated acute myocardial infarction, a dobutamine stress test was performed in 104 patients. Dobutamine was infused in doses of 5, 10, 15 and 20 micrograms.kg-1.min-1 every 5 min with ECG and blood pressure control. It induced a substantial increase in heart rate and systolic blood pressure. The patients were divided into 4 groups: (1) anterior (n = 28); (2) inferior (n = 32); (3) posteroinferior (n = 27) and (4) high lateral plus anterior or anterolateral (n = 17) infarction. They were followed for 2 to 18 months (mean 7.5 +/- 5). In basal conditions the ST segment was elevated in 49 patients and depressed in 20. Combined ST elevation and depression was seen in 11. After dobutamine there was ST elevation in 80 patients, depression in 71 and combined elevation and depression in 60. The magnitude of the maximal ST elevation was correlated with the magnitude of the maximal ST depression in each group of patients. There was a good inverse linear correlation between ST segment shifts in inferior vs high lateral leads, and ST depression was considered as a benign mirror image of opposite ST elevation in such leads. In patients with posterior infarction, anterior ST depression was considered as a mirror image of posterior ST elevation. In the remaining cases ST depression was a criterion of positivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915428 TI - Dose-related antiarrhythmic effects of nicainoprol in patients with chronic ventricular arrhythmias--a double-blind, placebo-controlled, cross-over multicentre trial. Nicainoprol Study Group. AB - One hundred and three patients with a history of ventricular arrhythmia were screened by baseline 24-h Holter monitoring for a minimal mean number of 30 premature ventricular beats (PVB) per hour. One hundred and one patients were subsequently enrolled in a double-blind, cross-over trial, including four 4-day periods with administration of placebo (PL) or nicainoprol (N.) in doses of 200, 400, 600 mg three times daily in randomized order. Antiarrhythmic efficacy could be evaluated in 61 patients who met all requirements of the protocol, including a complete sequence of valid Holter recordings (greater than 18 h each). Total PVBs were significantly reduced by the 400-mg dose (65%) and the 600-mg dose (71%) as compared to baseline. Two hundred mg N. and PL led to a non-significant reduction of PVBs by 41% and 24%, respectively. An individual response, assumed where there was simultaneous reduction of total PVBs greater than 75%, of ventricular pairs greater than 90% and elimination of ventricular runs, was found in 6 (10%), 10 (16%), 21 (34%), and 22 (36%) patients with PL, 200 mg N., 400 mg N. and 600 mg N., respectively. Four hundred and 600 mg N, significantly prolonged the PR interval (0.17 s and 0.18 s; median values) as compared with baseline (0.16 s), while the QRS duration was significantly increased only by the 600-mg dose (from 0.10 to 0.11 s). Heart rate, mean blood pressure, QT and JTc intervals were not significantly influenced by any dose of N.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915430 TI - Acute administration of captopril lowers the natriuretic and diuretic response to a loop diuretic in patients with chronic cardiac failure. AB - Angiotensin-converting enzyme inhibitors suppress plasma concentrations of the sodium retaining hormones angiotensin II and aldosterone. This action should potentiate the natriuretic and diuretic effects of loop diuretics. Some studies indicate, however, that the introduction of angiotensin-converting enzyme inhibitors for the treatment of cardiac failure is associated with transient weight gain and the development of oedema. We have compared the natriuretic and diuretic response to intravenous frusemide 40 mg alone with the natriuretic and diuretic response to intravenous frusemide 40 mg following the administration of a single dose of captopril in 12 supine male patients with stable chronic cardiac failure. Captopril lowered the 4 h diuretic response to frusemide from 1160 (60) to 685 (77) ml (P less than 0.05) and the natriuretic response from 120 (9.6) to 68 (11.7) mmol (P less than 0.05). Creatinine clearance fell after captopril from 91 (7.2) to 57 (7.7) ml min-1 (P less than 0.05). Systolic and diastolic blood pressures were lower after the administration of captopril but these changes were not significant. Plasma renin activity rose from 3.8 (1.04) to 12.34 (2.94) ng ml h-1 (P less than 0.05) and plasma angiotensin II was reduced from 24.9 (5.05) to 8.14 (1.8) pg ml-1 (P less than 0.05). Plasma aldosterone concentrations were not significantly lower following captopril. Angiotensin-converting enzyme inhibitors cause an acute fall in creatinine clearance which may reduce the effects of loop diuretics and attention must be paid to diuretic dosage when initiating angiotensin-converting enzyme inhibitors for the treatment of cardiac failure. PMID- 1915431 TI - Left ventricular dynamics and plasma catecholamines during isometric exercise in patients following cardiac transplantation. AB - Haemodynamics and plasma catecholamine responses to isometric exercise were evaluated invasively in 11 orthotopic heart transplant recipients and seven control subjects. Differences in haemodynamic responses between the two groups were already apparent after one min of handgrip at 30% of maximal voluntary contraction, and very pronounced at the end of the fourth minute. At this point transplanted patients showed smaller increments in heart rate (4.8 +/- 3.2 vs 20.4 +/- 14.1 beats.min-1, P less than 0.001), mean arterial pressure (13.7 +/- 7.2 vs 31.5 +/- 12.2 mmHg, P less than 0.001) and cardiac index (0.51 +/- 0.22 vs 1.02 +/- 0.53 L.min-1.m-2, P less than 0.01), whereas left ventricular end diastolic pressure increased to a greater extent (8.8 +/- 4.9 vs 2.2 +/- 1.8 mmHg, P less than 0.01). Stroke volume index increased similarly (3.8 +/- 1.8 vs 2.0 +/- 3.5 ml beat-1.m-2, NS) and systemic vascular resistance remained unchanged in both groups. The slopes of the left ventricular function curves (ratio of change in left ventricular work to change in left ventricular end diastolic pressure) indicated depressed left ventricular function in the transplanted patients. The two groups showed similar increments in mixed venous plasma norepinephrine and epinephrine indicating normal sympathoadrenal activation in the transplanted patients. In conclusion, transplanted hearts respond to handgrip with attenuated increases in heart rate, cardiac output and arterial pressure and by increasing left ventricular filling pressure, suggesting a poor contractile reserve probably due to denervation. Circulating catecholamines, especially epinephrine, probably contribute to the cardiac responses to isometric exercise. PMID- 1915432 TI - The early phenomena of restenosis following percutaneous transluminal coronary angioplasty. AB - In man the early onset of fibrocellular tissue reaction, which leads to restenosis following an initial successful percutaneous transluminal coronary angioplasty, has been poorly documented because of limited opportunities to study this phenomenon. The present study focused on early changes in seven patients who died within 20 days of a percutaneous transluminal coronary angioplasty procedure. Differences in the mode of laceration were noted between concentric and eccentric plaques. In the former, tears occur at the thinnest site of the plaque or within an already attenuated fibrous cap. The injury usually remains limited to the plaque. In eccentric lesions lacerations tend to occur in the non atherosclerotic wall segment, affecting the musculoelastic layers and the media. A further site of predilection is the border zone between the non-affected wall and the plaque. Early tissue response is characterized by fibrin-platelet depositions, and a proliferation of macrophages and spindle-shaped cells. The latter express the immunocytochemical characteristics of smooth muscle cells. However, differences occur according to the type of tissue injured. Laceration of the musculoelastic layers or media causes a rapid and extensive cellular response. Injury to an atheroma, on the other hand, mainly causes plaque fissures with either mural thrombosis and total luminal obstruction, extensive plaque haemorrhage or a 'wash-out' of the atheromatous debris. In the latter case the lining of the 'crater' shows an accumulation of macrophages and, once more, a proliferation of spindle-shaped cells. The present observations support the concept that the early response is due to an interaction of platelet-fibrin thrombus and smooth muscle cells, with a possible role for macrophages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915433 TI - Analysis of 100 emergency aortocoronary bypass operations after percutaneous transluminal coronary angioplasty: which patients are at risk for large infarctions? AB - Severe vascular complications are an inherent risk of percutaneous transluminal coronary angioplasty (PTCA). Data from 100 emergency aortocoronary bypass operations required after 2850 interventions (3.5%) were retrospectively analysed in order to identify factors that determine postoperative infarct size. Large infarctions were assumed if the patient died of cardiogenic shock (n = 12), if postoperative angiography demonstrated a decrease in left ventricular ejection fraction of more than 20% of if R-waves in the ECG decreased by more than 40% and a QRS-score increased by more than 5. According to these definitions, 29 patients experienced large infarctions, while 71 experienced no or only small infarctions. The following factors differentiated the two groups: age (58 vs 53 years, P = 0.008), pre-PTCA exercise work load (88 vs 118 Watts, P = 0.0001), exercise ischaemia score (2.7 vs 1.9, P = 0.045), degree of pre-PTCA stenosis (83 vs 86%, P = 0.03), coronary multivessel versus single vessel disease (60 vs 38%, P = 0.02), collaterals to the target vessel (10 vs 34%, P = 0.05), total vascular occlusion during PTCA (76 vs 56%, P = 0.035), and long duration of ischaemia after onset of the complication (253 vs 179 min, P = 0.012). Data from patients with large postoperative infarctions who survived ranged between those with no or small infarctions and those who died of cardiogenic shock. Higher age (P = 0.04), reduced exercise tolerance (P = 0.0004), absence of collaterals (P = 0.04), and duration of ischaemia until reperfusion (P = 0.001) were independent predictors of large postoperative myocardial infarctions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915435 TI - Pericardial effusion from self-inserted needle in the heart. PMID- 1915434 TI - Progression and regression of atherosclerosis, what roles for LDL-cholesterol and HDL-cholesterol: a perspective. AB - Numerous observational and intervention studies have shown that total (and LDL) cholesterol levels correlate positively with progression of atherosclerosis. It has also been shown that a mean low HDL cholesterol level is a potent predictor of CHD (coronary heart disease) in populations in which atherosclerotic diseases are prevalent. Recently, studies based on repeat angiographic examination, which are reviewed here, have shed new insight on the different roles that total cholesterol (or LDL) and HDL-cholesterol play on progression and regression of coronary atherosclerosis, respectively. From an epidemiological viewpoint, based on observational as well as intervention studies, the theory emerges that progression correlates best with total (and LDL-) cholesterol and that regression correlates best with HDL-cholesterol. The working hypothesis, if confirmed, will have practical implications for primary and secondary preventive measures. PMID- 1915436 TI - The kidney in congestive heart failure. AB - Congestive heart failure (CHF) is characterized by activation of (i) vasopressor and antinatriuretic influences (ii) and by counter-activation of vasodilator natriuretic systems. The former comprise the sympathoadrenal, renin-angiotensin aldosterone and arginine vasopressin systems, and possibly endothelin and withdrawal of endothelium dependent relaxing factor respectively. The latter include the prostaglandins (PGE-2, PGI-2), dopamine and atrial natriuretic factor. The response of the kidney to chronic heart failure, i.e. vasoconstriction and antinatriuresis, resembles the renal reaction to volume depletion. The adverse renal effects of ACE inhibitors in some patients with advanced congestive heart failure may be explained by lowering of renal perfusion pressure and dependence of glomerular filtration rate on angiotensin II. PMID- 1915437 TI - Time-constant adaptations in heart failure. AB - The circulatory compensatory mechanisms designed to cope quickly with physiological stress (e.g. sympathetic nervous system and the Frank-Starling mechanism) are less effective when there is chronic pathological stress, such as congestive heart failure (CHF). Other mechanisms come into play that operate over a longer time (e.g. activation of the renin-angiotensin-aldosterone system, myocardial hypertrophy and physiological deconditioning). Changes in blood vessels and skeletal muscle metabolism that result from inadequate delivery of oxygenated blood to working muscles belong to the group of mechanisms that develop slowly. When CHF therapy is successful, the abnormalities produced by this latter group of mechanisms will improve, but slowly. The concept that compensatory mechanisms have either short or long time constants for activation and reversal may explain why exercise tolerance improves much later than haemodynamics, which can be reversed acutely with vasodilator therapy. PMID- 1915438 TI - Mechanics of contraction and relaxation of the ventricle in experimental heart failure produced by rapid ventricular pacing in the conscious dog. AB - A model of heart failure produced by rapid ventricular pacing in the conscious dog instrumented with a conductance catheter to monitor instantaneous left ventricular volume has been developed. This experimental model is capable of analysis of the left ventricular pressure-volume relationship on a beat-to-beat basis, and has been used to assess ventricular function serially in the progress of heart failure and effects of pharmacological intervention. In seven dogs the magnitude of cardiotonic effects were significantly attenuated after development of heart failure. These findings support the concept that in the failing heart there is subsensitivity to beta-adrenergic stimulation in proportion to the severity. The failing heart was characterized by incomplete left ventricular relaxation. Dobutamine improved left ventricular early relaxation but did not affect chamber distensibility. In contrast new phosphodiesterase inhibitor, E 1020, improved ventricular distensibility with less marked changes in active relaxation; improved left ventricular relaxation appeared to be mediated by increased systolic shortening with enhancement of internal restoring forces, and improved distensibility by accelerated function of sarcoplasmic reticulum through increased intracellular cyclic AMP. PMID- 1915440 TI - Inflammatory heart disease. PMID- 1915439 TI - Perspectives of drug therapy in heart failure. AB - Despite an increasingly wide range of therapeutic options in heart failure management, fatality rates and morbidity remain high and new and better drugs are still needed. Assessing drug efficacy, and comparing two drugs, is difficult. Studies with mortality as an endpoint need to be large and long-term, and studies using exercise tolerance as an endpoint have inherent problems of design and execution. Although haemodynamic measurements are useful in assessing acute drug effects they are not helpful in the chronic state and a 'surrogate' endpoint for assessing heart failure is needed. Measurements of calf blood flow at rest and after exercise provide results that correlate with the patient's clinical state and response to therapy. Measurements of calf blood flow and treadmill exercise time were found to be useful in comparing the effects of ibopamine with captopril in patients with chronic heart failure. PMID- 1915441 TI - The value of endomyocardial biopsies in myocarditis and dilated cardiomyopathy. AB - Since the introduction of the bioptome in 1962, examination of fresh endomyocardial tissue has been undertaken progressively in many centres despite the misgivings of some investigators. In my own experience, I have examined biopsies from 3225 patients, of whom 1978 were suspected to have dilated cardiomyopathy. Of these patients, 549 showed evidence of myocarditis. Categorization into active (acute), resolving (healing) and resolved (healed) stages is important because of therapeutic implications. It is concluded that endomyocardial biopsies are of immense value in dilated cardiomyopathy where the relationship with myocarditis has become established. Even though in many cases only non-specific features are found, biopsy excludes those conditions that can result in a hypertrophied, dilated heart. Biopsy also forms the baseline for further investigations, such as virological, immunological, morphometric analyses and distinction from alcohol effects, all of which have thrown light on the pathogenetic mechanism of dilated cardiomyopathy. PMID- 1915442 TI - Endomyocardial biopsy findings in cases with pericarditis or perimyocarditis. AB - In order to determine the presence or absence of myocarditis in cases with viral or idiopathic pericarditis, a study was conducted as one of our series on endomyocardial biopsy. There were two groups of patients, pericarditis cases (n = 8), and patients with perimyocarditis (n = 6). In the former group, it was confirmed that cardiac sarcoplasmic enzymes were not released during the acute stage of the disease. In the latter, there was positive evidence of the enzyme release. Also, employing our method of categorizing the possibility of myocarditis at the histopathological level, we found that the category 'highly suggestive' of myocarditis was absent in all eight cases with pericarditis. However, in cases with perimyocarditis, this category was assigned in four out of six cases (67%), indicating a high incidence. The category, 'slightly suggestive', was seen in three cases of the former (38%) and two cases of the latter group (33%). It is concluded that in patients with pericarditis, the release of cardiac sarcoplasmic enzyme is an important diagnostic element in the diagnosis of perimyocarditis even if the clinical features reveal a predominance of pericarditis. In patients with perimyocarditis, progression to residual cardiac disease, such as conduction disturbance or congestive heart failure, is likely. PMID- 1915443 TI - Dilated cardiomyopathy and myocarditis: monoclonal antibodies to diseased heart tissues. AB - This study looked for the presence of abnormal contractile protein antigens and alterations in contractile protein expression in dilated cardiomyopathy (DCM). Monoclonal antibodies were raised to extracts from hearts removed at cardiac transplantation from two patients with dilated cardiomyopathy (DCM), and one with myocarditis. The specificities of the antibodies were assessed on cryostat sections from eight hearts with DCM. Although an extensive search was made for DCM-specific antibodies among over 1500 clones, none were found. However, a panel of antibodies was prepared and characterized, including antibodies to human adult myosin heavy chain beta, actin and troponin-I, which were selected for their value as reagents for immunocytochemical studies on cardiac, skeletal and smooth muscle. No significant alteration in the distribution of the epitopes recognized by these antibodies was found in DCM although more atrial myocytes in patients with DCM contained myosin adult heavy chain-beta. As a similar increase was found in atria from patients with other diseases who had a normal filling pressure, it was concluded that this alteration was unrelated to filling pressure, and was not specific for DCM. Further work with well defined monoclonal antibodies to other cardiac components in DCM could be useful in defining the alterations which lead to the functional defects in DCM and other cardiac diseases of unknown cause. PMID- 1915444 TI - Expression of MHC class I and II antigens and the Il-2 receptor in rejection, myocarditis and dilated cardiomyopathy. AB - In myocarditis and dilated cardiomyopathy a secondary immunopathogenesis is likely, since alterations to the humoral and cellular immune system have been repeatedly demonstrated. In rejection after heart transplantation activation of the immune system has been clearly seen. This may be comparable to myocarditis and thus could be a model for inflammatory heart disease. This study was set up to investigate whether an increased expression of antigens of the major histocompatibility complex and of the Il2 receptor in endomyocardial biopsies of patients after cardiac transplantation, myocarditis and dilated cardiomyopathy takes place. Cryostat sections were investigated immunohistologically by the immunoperoxidase test. There was an expression of class II antigens (HLA-DR, HLA DP, HLA-DQ) in acute rejection and in myocarditis and in some patients with dilated cardiomyopathy on endothelial cells, interstitial cells but not on the myocytes. The results for class I (HLA-A, B, C) are similar, but in addition an expression on myocytes was observed in myocarditis and rejection. A second immunopathogenesis is most likely in some patients with dilated cardiomyopathy. The expression of the Il2 receptor on interstitial cells as a specific marker of cell activation was only seen in acute rejection and in some cases of myocarditis. PMID- 1915445 TI - Immune response to the endothelium in myocarditis, dilated cardiomyopathy and rejection after heart transplantation. AB - The role of endothelial cells in inflammatory heart disease and rejection after heart transplantation is only partly understood. To determine whether an immune reaction against endothelial cells occurs we examined endomyocardial biopsies from patients with myocarditis (n = 13), dilated cardiomyopathy (n = 23), no clinical rejection (n = 10) and moderate to severe rejection after heart transplantation (n = 10). These were compared to 'normal' donor hearts with monoclonal endothelial-specific antibodies EN4, Pal-E and F VIII-related antigen. Nearly all endothelial cells were stained positively with EN4. There were no significant changes in the binding of the antibodies except in rejection when Pal E and F VIII-related antigen were significantly increased. It is concluded that apart from their possible role as antigen-presenting cells, endothelial cells are important targets in rejection after heart transplantation. Damage or cytolysis of endothelial cells may cause both altered transendothelial permeability and functional decrease in antigen presentation. PMID- 1915446 TI - Serum neopterin--possible immunological marker of myocardial inflammation in patients with dilated heart muscle disease. AB - Measurement of neopterin in biological fluids is a sensitive and specific tool for detecting activation of the T cell/macrophage system. Serum neopterin level, detected by radioimmunoassay, and data from morphological investigations of myocardium were compared in 29 patients with a clinical diagnosis of dilated heart muscle disease. According to the results of endomyocardial biopsy (22 cases) and autopsy (seven cases), 14 patients had morphological features of myocarditis, 13 dilated cardiomyopathy and two a fibrotic subtype of dilated cardiomyopathy (DCMP). The mean neopterin level in all patients (12 +/- 9 nM l-1) was higher than in the control group (5 +/- 2 nM l-1) (P less than 0.05). Also, the mean neopterin level was significantly higher in patients with myocarditis and fibrotic subtype of DCMP (16 +/- 11 nM l-1) than in patients with a morphological diagnosis of DCMP (9 +/- 6 nM l-1) (P less than 0.05). The highest neopterin levels in both groups were found in those who subsequently died during follow-up (mean level 23 +/- 10 nM l-1). There was a correlation between neopterin and beta 2-microglobulin (r = 0.83, P less than 0.05). Our study suggests that the raised serum neopterin level may be a marker of myocardial inflammation and unfavourable prognosis in patients with a clinical diagnosis of dilated heart muscle disease. PMID- 1915447 TI - Release of oxygen free radicals by macrophages and neutrophils in patients with rheumatic fever. AB - The generation of oxygen free radicals (OFR) by peripheral blood monocytes and neutrophils of patients with rheumatic fever (RF) and rheumatic heart disease (RHD) has been studied using the luminol-enhanced chemiluminescence technique. The mechanism of OFR generation was studied by measuring NADPH oxidase enzyme activity. The effect of substrate was studied by measuring the hexose monophosphate (HMP) shunt enzymes: glucose-6-phosphate dehydrogenase and 6 phosphogluconate dehydrogenase. Three groups of patients [i) recurrent rheumatic activity, (ii) chronic RHD, (iii) acute pharyngitis) and normal controls were studied at day 0 and followed-up serially at 15, 90 and 180 days. The release of OFR, was significantly higher (P less than 0.001) in patients with recurrent rheumatic activity than in those with acute pharyngitis or chronic RHD, throughout the study period. A significant decline (P less than 0.001) in OFR release was observed from day 0 to day 180 in these patients, whereas no such change was observed in the chronic RHD group. This study raises the possibility that these phagocytic cells, which infiltrate the myocardium, may through generation of OFR, have a role in the pathogenesis of cardiac damage seen in patients with RHD. PMID- 1915448 TI - Experimental giant cell myocarditis induced by cardiac myosin immunization. AB - To identify a cardiac protein that could cause a serious autoimmune myocarditis, membranous proteins and myosin as antigens were investigated. In mice immunized with membranous proteins, the lesions induced were limited on the histological level. On the other hand, in Lewis rats immunized with cardiac myosin, serious myocarditis was induced. Every rat showed evidence of heart failure which was fatal in a few. Histology disclosed extensive cell infiltrates and myocardial necrosis. Among those lesions, giant cells were present. This myocarditis could be also transferred adoptively by lectin-activated spleen cells, T-lymphocytes, but not by IgG fraction. Thus, cardiac myosin can induce autoimmune giant cell myocarditis in Lewis rats. PMID- 1915449 TI - Myopathies and cardiomyopathies: histochemical and biochemical analyses. AB - The most frequent muscle diseases affecting the heart are muscular dystrophies and myotonic dystrophy. Apart from congenital heart diseases, various metabolic disorders are characterized by cardiac involvement. Potent candidates are carnitine deficiency, beta-oxidation deficiencies, and mitochondrial myopathies such as Kearns-Sayre syndrome. A typical example of an anaerobic metabolic myopathy causing cardiomyopathy is acid maltase deficiency. For diagnosis, ECG and echocardiography as well as cardiac catheterization should be performed and, if indicated, a heart muscle biopsy should be carried out. Diagnosis of the underlying disease should be possible from skeletal muscle biopsy. Besides routine staining, histology should include specific stainings for glycogen, lipids and mitochondrial activity or dystrophin. If certain histochemical abnormalities are found indicating a metabolic disorder, biochemistry is helpful for final diagnosis. PMID- 1915450 TI - Myocardial catecholamine concentrations in dilated cardiomyopathy and heart failure of different origins. AB - Myocardial catecholamine concentrations were determined in endomyocardial biopsies from patients with heart failure to assess if tissue catecholamine levels relate to the severity of myocardial damage or the aetiology of the underlying disease. Methodological studies revealed a good reproducibility of catecholamine determinations in biopsies; the variance between paired biopsies was below 17% when myocardial catecholamines were related to non-collagen protein (NCP). Myocardial norepinephrine (in pg micrograms-1 NCP) levels were comparable in patients with dilated cardiomyopathy (DCM, 5.3 +/- 3.4, n = 22) and in patients with coronary or valvular heart disease (5.6 +/- 4.7, n = 14). In both groups, a significant reduction of myocardial norepinephrine was found (controls 12.0 +/- 3.4, P less than 0.0006). In a subgroup of patients with heart failure and a LVEF less than 30% (3.9 +/- 3.5, n = 17) myocardial norepinephrine content was lower than in patients with heart failure and LVEF of 31-55% (6.6 +/- 3.4, n = 19) (both P less than 0.05 against controls: 12.0 +/- 3.4, n = 16). A correlation between myocardial norepinephrine and LVEF was found in DCM (P less than 0.001, r = 0.70). The loss of myocardial norepinephrine is a characteristic feature of heart failure. It is independent of the origin of failure, but correlates with the impairment of LV function. PMID- 1915451 TI - Diastolic dysfunction as a precursor of myocardial damage by reoxygenation. PMID- 1915452 TI - Clinical aspects and haemodynamics in the follow-up of dilated cardiomyopathy and myocarditis. AB - Many studies on the natural history of dilated cardiomyopathy show high probability of death or of cardiac transplantation in a large percentage of patients. These studies have several methodological limitations. Our prospective study, carried out from 1971, and which evaluated 120 patients, showed improved survival in more recent years. Survival 3 years after diagnosis changed from 30% (1971-6/1981) to 88.4% (7/1986-1/1989). Thirty patients were investigated by haemodynamic exercise test to assess their haemodynamic behaviour during exercise, to evaluate the effects of pharmacological treatment and to define parameters of prognostic value. Different haemodynamic behaviours were observed. Haemodynamic investigation during exercise is useful to assess the effect of treatment and may have prognostic value. Myocarditis presents a spectrum of clinical symptoms and echocardiographic abnormalities. In patients with congestive heart failure left ventricular dysfunction is common. Patients with atrioventricular block or chest pain usually have good left ventricular function. During follow-up, improvement is possible but persistent left ventricular dysfunction is associated with a high mortality rate. When left ventricular function is good at presentation and does not deteriorate during follow-up the prognosis is good. PMID- 1915454 TI - Right ventricular cardiomyopathy: is there evidence of an inflammatory aetiology? PMID- 1915453 TI - Pericardioscopy--a new diagnostic tool in inflammatory diseases of the pericardium. AB - Pericardioscopy is a new diagnostic tool to visualize macroscopically alterations in both the epicardium and pericardium. The first experience in 30 patients is reported, after pilot investigations were carried out in experimental animals. After puncture of the pericardial effusion a 9F sheath was introduced under echocardiographic and/or x-ray control. The fluid was removed by aspiration and 100-150 ml of body warm saline were infused in the pericardial sack. A flexible 8F fiberglass instrument (Vantec, Baxter or Storz) and a rigid 110 degree 8F endoscope (Storz) were used for visualization of peri- and epicardium and for video documentation. Complementary to visualization, optically-guided and controlled epicardial and pericardial biopsies were performed and analysed further. Specific diagnosis of pericardial effusion is thus greatly facilitated by the triad, pericardioscopy, cytology and epicardial as well as pericardial biopsy. PMID- 1915455 TI - Sarcoid heart disease--results of follow-up investigations. AB - 52 patients thought to have sarcoid heart involvement have been followed up. By administration of a standardized glucocorticoid therapy we demonstrated improvement of patients' symptoms, ECG disturbances, thallium scan defects of left heart muscle and there was 60-70% regression of pulmonary sarcoidosis. There was a low death rate. We conclude that our diagnostic measures are reliable, and that glucocorticoid therapy is efficacious in the early stages of the disease. PMID- 1915456 TI - Diagnostic assessment of macrophage phenotypes in cardiac transplant biopsies. AB - Forty-one endomyocardial biopsies of the right interventricular septum have been investigated in 24 immunosuppressed patients after orthotopic heart transplantation. Monoclonal antibodies 27E10, 25F9, and RM3/1, which react with different macrophage phenotypes, and antisera MRP-8 and MRP-14, specific for proteins expressed on endothelial and monocyte cell surfaces in inflammation as well as markers for CD4+ and CD8+ T-lymphocytes, were employed in an indirect immunoperoxidase staining technique. This methodology permits more physiological recognition of the inflammatory process within the myocardium. It was possible to verify and to distinguish acute early, late and down-regulatory stages of inflammation in 33 biopsies (80%). No evidence of inflammation was found in seven biopsies (17%). Conventional histopathology with haematoxylin-eosin and Masson's trichrome was performed simultaneously, and demonstrated inflammation to be present in 23 of 41 biopsies (56%). An important findings is that CD4+ and CD8+ lymphocytes were absent in 15 of 41 specimens (37%) although there was inflammation proven by the presence of different macrophage phenotypes. The results indicate the necessity of long-term serial investigations of the physiological role of specific inflammatory macrophage phenotypes during the rejection process. It is concluded that the phenotyping of macrophage and endothelial cell differentiation antigens offers a sensitive approach to assess diagnosis of myocardial inflammation as a consequence of ongoing rejection in cardiac allografts. PMID- 1915458 TI - Contractile responses of myocytes isolated from patients with cardiomyopathy. AB - Single cardiac myocytes isolated from failing and non-failing human ventricles were superfused at 32 degrees C and electrically stimulated at 0.2 Hz. Their contraction amplitude and velocities of contraction and relaxation were continuously during challenge with isoprenaline or high extracellular calcium. Action potentials were monitored with intracellular microelectrodes, and calcium transients followed using the fluorescent dye fura-2. Changes in contractility were correlated with severity of disease, as defined by New York Heart Association class, dose of diuretics, left ventricular ejection fraction and left ventricular end-diastolic pressure. Beta-adrenoceptor desensitization was detected in these cells as a decreased response to isoprenaline relative to that of calcium in the same cell. Significant correlations were obtained between reduction of beta-adrenoceptor sensitivity and all four indicators of disease severity. No correlation between the maximum contraction amplitude in high extracellular calcium and severity of disease was observed, the same was true for contraction and relaxation velocity in high calcium. Some significant decline in contractility with age of the patient was noted. Analysis with respect to aetiology of disease showed a subpopulation with dilated or hypertrophic cardiomyopathy where relaxation of the single cells was impaired. This was related to a prolonged calcium transient and action potential. Isoprenaline accentuated the lengthened second phase of relaxation, whereas high extracellular calcium reduced it. These interventions had similar effects on action potential duration. The actions of isoprenaline and calcium were similar on cells from failing and non-failing human hearts and on normal guinea-pig myocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915457 TI - Impaired myocyte function in vitro incubated with sera from patients with myocarditis. AB - Sera positive for antimyolemmal antibodies (AMLAs) from patients with acute biopsy-proven myocarditis exerted a cytotoxic effect on cardiocytes stimulated in vitro. Using an edge-detecting system, contraction amplitude and contraction velocity were altered after the addition of AMLA-positive sera when compared to sera from healthy controls. Antibodies alone did not change the functional parameters. Only the presence of complement and heart-reactive antibodies mediated the detrimental effects. This suggests that a complement-mediated antibody-dependent immune mechanism is operative in human myocarditis. PMID- 1915459 TI - The role of pericardiectomy in pericardial disorders. AB - Pericardiectomy today is an accepted therapeutic concept in patients with different pericardial disorders. The postoperative outcome of patients is mainly influenced by two factors. First, diagnosis has to be established early to avoid myocardial deterioration and secondary organ failure, especially of liver and kidneys. Second, the whole accessible surface of atria and ventricles has to be freed from diseased and calcified pericardium. To achieve this, we prefer a total median sternotomy for the surgical approach. In selected cases of acute pericardial effusion or as a palliative procedure, a small infrasternal incision or anterolateral thoracotomy is used for pericardiocentesis and creation of a pericardio-pulmonary window. Between January 1969 and March 1990 we treated 187 patients with different pericardial disorders. Mortality was 4.8% overall, and was especially low (2.8%) among the 106 patients with acute and chronic pericardial effusion. Out of 67 patients with constrictive pericarditis, four died during hospital stay (5.9%). The prognosis is still poor for patients with primary or secondary malignant pericardial tumours, in whom surgery is mostly restricted to palliative resection, and a special group with constrictive and mostly calcified epicarditis, for whom no surgical option is available. PMID- 1915460 TI - Lyme borreliosis as a cause of myocarditis and heart muscle disease. AB - Lyme borreliosis (LB) is a multisystem disorder that may cause self-limiting or chronic diseases of the skin, the nervous system, the joints, heart and other organs. The aetiological agent is the recently discovered Borrelia burgdorferi. In 1980, cardiac manifestations of LB were first described, including acute conduction disorders, atrioventricular block, transient left ventricular dysfunction and even cardiomegaly. Pathohistological examination showed spirochaetes in cases of acute perimyocarditis. Recently, we were able to cultivate Borrelia burgdorferi from the myocardium of a patient with long standing dilated cardiomyopathy. In this study, we have examined 54 consecutive patients suffering from chronic heart failure for antibodies to Borrelia burgdorferi. On ELISA, 32.7% were clearly seropositive. The endomyocardial biopsy of another patient also revealed spirochaetes in the myocardium by a modified Steiner's silver stain technique. These findings give further evidence that LB is associated with chronic heart muscle disease. PMID- 1915461 TI - Prognostic determinants in conventionally treated myocarditis and perimyocarditis -focus on antimyolemmal antibodies. AB - In this study from two specialized centres 85 patients with histologically proven myocarditis (n = 10) and clinically ascertained perimyocarditis (pericardial effusion and cardiomegaly or segmental wall motion abnormality; n = 75) were followed up for 4.5 + 1.9 years. Immunosuppressive treatment was not applied. After a mean follow-up period of 4.5 + 1.9 years 55% of patients had improved clinically and 35% of patients were completely free of symptoms. Relapses had occurred up to three times. Chronic forms were found in 20% of patients, mostly in those with pericarditis and effusions. Eighteen percent of the patients deteriorated gradually. In 20% of the chronic or deteriorating patients congestive heart failure developed (postmyocarditic heart muscle disease). Fifteen percent of the patients died, mainly from bacterial perimyocarditis and to a lesser extent from inflammatory heart disease from enteroviruses. Patients who succumbed after more than 6 months died either suddenly or from progressive heart failure. A favourable outcome was often accompanied by a decrease in titre, but this decrease was less impressive in those who had antimyolemmal and antisarcolemmal antibodies. The persistence of these antibodies in high titres predominated in patients with poor prognosis and postmyocarditic dilated heart muscle disease, as did cytolytic serum activity. PMID- 1915462 TI - Humoral immune response against contractile proteins (actin and myosin) during cardiovascular disease. AB - Sensitive and highly specific ELISA assays were developed to determine humoral immune response against actin and myosin in 122 patients suffering from various cardiovascular diseases: acute viral myocarditis (n = 10, MYO), acute myocardial infarction (n = 28, AMI), valve surgery (n = 35, VALVE), coronary bypass surgery (n = 35, CABG), and peripheral vascular surgery (n = 14, VASC). Anti-actin and anti-myosin antibodies were determined on admission and serially during a period of 90 days. Anti-actin and anti-myosin immune response (IgG, IgM) was expressed comparing absorbance of the patients' serum with a reference serum. In the different patient groups significantly (P less than 0.01) higher anti-actin and anti-myosin antibody concentrations were found on admission compared with age matched control groups. During follow-up, all patient groups except the vascular surgery group showed a significant immune response against actin and myosin, with an immune response ratio (peak/admission) for AMA IgG and IgM respectively of 2.12 and 2.40 in the VALVE group, 1.30 and 1.99 in the CABG group, 1.42 and 1.48 in the AMI group and 1.66 and 1.25 in the MYO group; and for AAA IgG and IgM respectively of 1.57 and 3.00 in the VALVE group, 1.54 and 1.64 in the CABG group, 1.25 and 1.07 in the AMI group, and 1.42 and 1.42 in the MYO group. A significant correlation between pre-cardiac injury and peak post-cardiac injury anti-myosin and anti-actin autoantibody levels could be demonstrated suggesting that pre-injury sensitization to these antigens plays an important role in evoking post-cardiac injury immune response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915463 TI - Biochemical changes in endometrial carcinoma and their correlation to clinical outcome and prognosis. AB - Four biochemical parameters, soluble oestradiol (REC) progesterone (RP) receptors, 17B oestradiol and isocitric dehydrogenase enzymes were studied to evaluate hormone sensitivity in 51 patients with endometrial carcinoma. Samples of tumours were taken before and after 7 to 14 days of oral medroxyprogesterone acetate (MPA) treatment for histological and biochemical analysis. Hormone sensitivity assessed by a decrease in receptor concentration after MPA in REC rich (p less than 0.005) and RP rich (p less than 0.02) tumours was 65% and 63% respectively. Induction of isocitric dehydrogenase enzyme with MPA was highly significant in REC rich (p less than 0.0001) and RP rich (p less than 0.001) tumours, as was the induction of 17B oestradiol dehydrogenase in REC rich (p less than 0.01) and RP rich (p less than 0.005), confirming progestogen sensitivity. Post MPA dehydrogenase enzyme levels predicted survival more accurately than pre MPA receptor status of the tumours. PMID- 1915464 TI - Pelvic malignancy presenting as a pelvic inflammatory process in pre and postmenopausal women. AB - Among two hundred and twenty-one patients admitted with the diagnosis of pelvic inflammatory disease (PID), 6 had an underlying malignancy. The rate of underlying malignancy was 1.4% in premenopausal patients and 42.8% in postmenopausal patients. This difference was statistically significant, p less than 0.001. In postmenopausal patients presenting with a pelvic inflammatory process pelvic malignancy should be highly suspected and thorough examination made. PMID- 1915465 TI - Postmenopausal extragenital choriocarcinoma. A case report and review of the literature. AB - A case is presented of extragenital abdominal choriocarcinoma without uterine lesion in a postmenopausal woman. Nineteen years after her antecedent pregnancy, a legal abortion, and thirteen years after her menopause, the patient was admitted to the hospital because of intermittent abdominal pain. Explorative laparotomy revealed a large tumour mass in the greater omentum, mesosigmoideum, peritoneal implants and metastatic growth to the serosal lining of the uterus and the wall of the stomach. Cytoreductive surgery was performed. The histopathological report showed an extrauterine, nongonadal pure choriocarcinoma. Immunoperoxidase stain was strongly positive for hCG and a raised serum beta-hCG level preoperatively confirmed the diagnosis. A polychemotherapy regimen was administered. However, after six months the beta-hCG levels increased rapidly. Liver, lung and mediastinal metastases were diagnosed. The patient's condition rapidly deteriorated and she expired one month later. The post mortem examination showed a far advanced extragonadal pure choriocarcinoma without any obvious primary origin. The implications for a possible origin of extragonadal nongestational choriocarcinoma are briefly discussed. PMID- 1915466 TI - Osteocalcin: a valuable bone metastasis marker. AB - Osteocalcin (BCG) in an osteoblast product which reflects the bone formation rate. It could be a valuable bone metastasis marker. To investigate this, we measured serum osteocalcin levels by using radioimmunoassay method in 11 healthy subjects and in 79 cancer patients. The cancer patients consisted of 36 non metastatic, 29 with only bone metastasis and 14 with extraosseous metastases. Significance was found only between bone metastatic patients and non-metastatic patients in both sexes (p. 0.05). There was no significance between non metastatic patients and patients with other than bone metastases. This study shows that osteocalcin measurements reflect bone formation rates in bone metastasis and could be used as a bone metastasis marker in suspicious cases. PMID- 1915467 TI - Acute renal failure associated with intraperitoneal cisplatin chemotherapy with systemic thiosulfate protection in ovarian cancer patients. AB - Acute renal failure associated with intraperitoneal cisplatin chemotherapy occurred in 4 courses of treatment each given to one patient, and comprised 3.4% of the total number of intraperitoneal treatment courses. The 4 patients recovered completely, 2 of them after dialysis. Several possible reasons for this complication, which occurred in spite of thiosulphate systemic protection, are considered. Strict adherence to the treatment protocol is mandatory in order to avoid severe nephrotoxicity. PMID- 1915468 TI - Ovarian neoplasm mimicking rectal carcinoma. Report of a case and review of the literature. AB - We report a rare case of primary endometrioid carcinoma of the ovary which presented clinically with rectal bleeding mimicking a rectal cancer. The patient's pre-operative evaluation included radiographic and sero-immunologic findings which indicated a primary ovarian neoplasm. Only two other cases of ovarian carcinoma with this presentation have been reported in the literature. Gynecologic processes that can present as bleeding gastrointestinal lesions are reviewed. PMID- 1915469 TI - Conservative surgery in vulvar-vaginal neoplasias and fertility. 3 clinical cases. AB - In this article we present three clinical cases of patients affected by vulvar neoplasm. Since the patients were very young when the disease was diagnosed, we decided for a conservative treatment. All patients underwent a surgical non mutilant therapy which guaranteed a surgical radicality and, at the same time allowed them a normal reproductive life. Later all patients conceived and their pregnancies developed physiologically till the end. One patient died 23 years later; the two other are still alive and disease-free. PMID- 1915470 TI - Is immunoprophylaxis of cancer possible? AB - With the three modalities of cancer treatment, surgery, radio- and chemo-therapy, even when applied in optimal conditions, over 50% of patients remain incurable because of metastatic disease. Hence the importance of preventive methods of approach to cancer. Host human tumors arise in renewing cell populations, while others, which originate in tissues with a slower rate of proliferation, are often preceded by tissue injury, which induces an adaptive proliferation (irritants, viruses, hypoxia etc.). Prospective and retrospective studies have shown that a "precancerous lesion" (intraepithelial neoplasia), meaning a certain histopathological substratum which, when not disturbed in its natural history through diagnostic or therapeutic proceedings, can evolve in a significant proportion, to invasive cancer. Our earlier studies have revealed a specific host resistance to placental suspension (PS) when injected intradermally in patients with clinical conditions having, as histopathological substratum, an adaptive cellular proliferation. These findings suggest that a successful immunologic approach for adaptive proliferation is a boosted cell-mediated hypersensitivity reaction which, as an adjunct to other therapies, would eliminate and thus prevent the progression of adaptive proliferation towards neoplasia. A vaccine consisting of PS used as an immunogen, mixed with and adjuvant (BCG) may allow the strengthening of what is a natural but ineffective bodily response to the problem of adaptive proliferation. It is easier to eliminate immunologically an antigenic homogeneous cellular proliferation process than a neoplastic one which is antigenically heterogeneous. The induction of cell-mediated hypersensitivity reaction by a PS + BCG vaccine in healthy people would also be a primary immunoprophylaxis for some solid tumors in man.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915471 TI - Effects of atropine treatment on in vitro and in vivo binding of 4-[125I] dexetimide to central and myocardial muscarinic receptors. AB - Upregulation of muscarinic cholinergic receptors (mAChR) after chronic atropine treatment has been described previously. The present study was designed to evaluate 4-iodine-125 dexetimide as an agent to determine changes in the number of mAChR. Rats were injected subcutaneously with atropine (500 mg/kg) either once or chronically, once daily for 10 days, and sacrificed 24 h later. In vitro binding assays with 4-[125I]-dexetimide showed significant increases in the number of mAChR in cerebra (21%) and ventricles (45%) after chronic atropine treatment but not after acute treatment. The affinity of binding to cerebral and ventricular mAChR declined after acute and chronic atropine treatment. In vivo studies were carried out involving intravenous injection of 4-[125I]-dexetimide 24 h after atropine treatment. Binding was markedly reduced in the brain and heart. Upregulation of mAChR, as seen in in vitro studies, could not be observed because of the remaining atropine. Occupancy of mAChR by atropine persisted as long as 7 days after one dose. The results of these studies indicate that 4 [125I]-dexetimide binding reflects the effects of atropine on central and peripheral muscarinic cholinergic receptors in vitro and in vivo. PMID- 1915473 TI - Single photon emission tomography imaging of myocardial oxidative metabolism with 15-(p-[123I]iodophenyl) pentadecanoic acid in patients with coronary artery disease and aorto-coronary bypass graft surgery. AB - A total of 29 patients with coronary artery disease (CAD) were investigated with 15-(p-[123I] iodophenyl)pentadecanoic acid (123I-IPPA) and sequential single photon emission tomography (SPET). Of these, 19 were studied after aorto-coronary bypass graft surgery. Some 13 patients without evidence of CAD served as a control group. Two SPET studies (early and late) were carried out within 45 min after intravenous administration of 200 MBq 123I-IPPA at peak sub-maximal exercise. Semi-quantification of uptake (related to perfusion) and turnover (linked to metabolism) was obtained by segmental comparison of oblique slices. Taking coronary arteriography as the "gold standard", 123I-IPPA scintigraphy had the following figures of merit for sensitivity and specificity in the diagnosis of CAD: for the left anterior descending artery territory 93% and 95%, for the left circumflex artery region 96% and 92%, and for the right coronary artery territory 77% and 92%, respectively. In all, 90% of the reperfused myocardial segments showed an improvement of uptake. Of these, 61% exhibited increased turnover after revascularization and 39% had pathologic turnover and thus a dissociation of improvement of perfusion and oxidative metabolism after surgery. PMID- 1915472 TI - PET studies with L-[1-11C]tyrosine, L-[methyl-11C]methionine and 18F fluorodeoxyglucose in prolactinomas in relation to bromocryptine treatment. AB - Aspects of metabolism in prolactinomas were investigated by positron emission tomography using L-[1-11C]tyrosine, L-[methyl-11C]methionine and 18F fluorodeoxyglucose (18FDG). Using L-[1-11C]tyrosine, four patients were monitored prior to and 18 h after an injection of 50 mg bromocriptine. At 18 h after bromocriptine intervention, L-[1-11C]tyrosine uptake into tumour was reduced with 28% (P less than 0.07). A correlation analysis of the bromocriptine-induced decrease in L-[1-11C]tyrosine uptake and the reduction of serum prolactin levels indicated that the action of bromocriptine on prolactin synthesis and prolactin release is not coupled. In the untreated situation, the four patients were investigated with 18FDG as well, but the prolactinomas could not be visualized. Three untreated patients were studied with L-[methyl-11C]methionine. The tumour imaging potential of L-[methyl-11C]methionine and L-[1-11C]tyrosine appeared to be nearly equivalent for prolactinomas. Unlike prolactinoma tissue, the salivary glands showed a pronounced preference for L-[1-11C]tyrosine as compared to L [methyl-11C]methionine. L-[1-11C]tyrosine is a valuable tool to obtain information on the metabolism and treatment of prolactinomas. PMID- 1915474 TI - Demonstration of disturbed free fatty acid metabolism of myocardium in patients with non-insulin-dependent diabetes mellitus as measured with iodine-123 heptadecanoic acid. AB - Myocardial free fatty acid metabolism and left ventricular function were evaluated in 15 middle-aged patients with non-insulin-dependent diabetes mellitus (NIDDM) and in 8 healthy control subjects. The study subjects had no evidence of coronary heart disease on the basis of clinical history, exercise ECG or myocardial perfusion scintigraphy. During peak exercise, iodine-123 hepatadecanoic acid (HDA) was intravenously injected. Myocardial activity distribution of 123I-HDA was measured 10, 30, and 50 min after exercise using single-photon emission tomography (SPET); and then further corrected by free 123I iodine. Venous blood samples were drawn for detecting the plasma activity of 123I. The net extraction of 123I-HDA into the myocardium was obtained by dividing the corrected tissue 123I concentration by the integral of the plasma time activity curve. The net extraction was 0.40 +/- 0.06 min-1 (mean +/- SD) patients with NIDDM and 0.38 +/- 0.06 min-1 in control subjects (P greater than 0.1), respectively. The faster elimination rate of 123I-HDA was found in patients with NIDDM (0.029 +/- 0.008 min-1) than in control subjects (0.022 +/- 0.004 min-1; P less than 0.01). There was no statistically significant difference in left ventricular ejection fraction (LVEF) at rest between patients with NIDDM (53 +/- 9%) and control subjects (56 +/- 2%), whereas the increase of LVEF during exercise remained lower in patients with NIDDM (3.4 +/- 8.2%) than in control subjects (11.8 +/- 5.8%; P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915475 TI - Diagnosis of brain death with technetium 99m hexamethylpropylene amine oxime. AB - We report on the utility of technetium 99m hexamethylpropylene amine oxime (99mTc HMPAO) to diagnose brain death following cardiac surgery on a 49-year-old man with triple-vessel coronary artery disease. The imaging parameters and criteria to diagnose irreversible brain damage (brain death) with 99mTc-HMPAO are outlined. Brain imaging with this tracer seems to be more reliable than classic radionuclide angiography and has a potential value to confirm the diagnosis of brain death at an early stage. In addition, it may be used to evaluate the perfusion pattern to other vital organs with potential for transplantation. PMID- 1915476 TI - Testicular involvement of sarcoidosis diagnosed by gallium-67 scintigraphy. AB - Gallium-67 scintigraphy helped to determine the extent of systemic sarcoidosis and demonstrated testicular involvement in a 32-year-old black man who presented with ataxia, weight loss, and a left testicular mass. To our knowledge, this is the first case of testicular sarcoidosis demonstrated by gallium-67 scintigraphy in a patient with systemic sarcoidosis. PMID- 1915477 TI - Losses of gallium in common laboratory ware and ways to minimize them. PMID- 1915478 TI - Paediatric oncology in developing countries. AB - Paediatric oncology in developing countries is a specialty in its own right that has so far been largely neglected by the western medical profession. It has specific features of genetic cancer predisposition and of external factors influencing phenotypic cancer manifestations. We point out here some of the specific features of cancer presentation in children of developing countries. PMID- 1915479 TI - Caustic burns of the upper digestive and respiratory tracts. AB - In a series of 51 children presenting with an accidental caustic burn, symptoms were analysed for their predictive value of significant i.e. necrotizing oesophageal lesions (grade II or III). For the whole group, the incidence of significant oesophageal lesions was 37%. Vomiting and/or respiratory distress were associated with high incidence of significant oesophageal burn (84% and 75% respectively). The particular location of each caustic burn was analysed for its association with caustic burns at other anatomical sites. Of the 18 patients with a laryngeal burn, 72% also had a grade II or III oesophageal burn. The 19 patients with a grade II or III oesophageal burn and the 18 patients with a laryngeal burn, all had lesions at other sites. In the group of 19 patients with a caustic lesion limited to one site, only 1 patient showed mild oesophagitis (grade I) without late sequelae. PMID- 1915480 TI - Human leucocyte class I and II antigens in coeliac disease: a study in an Austrian paediatric population. AB - Regional variations in the human leucocyte antigen (HLA) distribution patterns of coeliac disease (CD) have been reported. This study focuses on phenotype frequencies of a cohort of Austrian paediatric CD patients in comparison with those recorded in the literature. HLA class I and II typing was performed in 136 CD patients and 667 healthy controls from the general population of the same geographical area. The HLA phenotypes of our controls agreed with those published for Caucasians. In our patients the relative risks (RR) were 6.43 for DR3 and 2.52 for DR7, the aetiologic fractions being 0.58 respectively 0.24. The highest RR (7.78) was found for DR3/DR7 heterozygotes. The RR for DR5 was increased in heterozygosities, either with DR3 (3.34) or DR7 (5.53), yet not for DR5 alone. Of our patients, 10% were lacking both DR3 and DR7 as well as B8, 82% of them were positive for DQw3. In these DR3 and DR7 negative patients, DR4 and DR5 were significantly more frequent than in the others. DR5 was also significantly more common in these patients compared to controls lacking the same antigens, whereas this did not hold true for DR4. Prospective studies are required to determine any link between these HLA heterogeneities and long-term progression of the disease. PMID- 1915481 TI - Final height in girls with untreated constitutional delay in growth and puberty. AB - During a 10-year period, 23 girls compared to 118 boys presented with constitutional delay in growth and puberty. Of these girls, 15 were followed to final height to determine the outcome of the untreated condition in terms of both growth and psychological well-being. At presentation chronological age was 13.2 (1.7) years [mean (S.D.)], bone age delay 2.7 (0.9) years, standing height standard deviation score (SDS) -3.4 (0.9), and predicted adult height (PAH) SDS 1.3 (0.7) (Tanner-Whitehouse II method). Final height SDS was -1.5 (0.8) measured at 18.9 (2.6) years of age. Mean age at menarche was 15.6 (0.9) years. There was no significant difference between final adult height (FH) and PAH but there was a significant difference between FH and target height (P less than 0.001). Psychological questionnaires revealed no significant difference in self-esteem, marital or employment status between the patient and control groups. There was no significant correlation between self-esteem and FH but 80% felt their growth delay had affected success either at school, work or socially. Of the patients, 50% would have preferred treatment to advance their growth spurt. This study demonstrates that girls with constitutional delay in growth and puberty reached their PAH, although this was lower than the midparental heights. The girls also experienced significant distress due to delayed growth and puberty and treatment to advance growth should be considered more frequently. PMID- 1915482 TI - Exercise performance in very low birth weight children at the age of 7-12 years. AB - Fifteen very low birth weight children, 9 appropriate for gestational age (AGA, mean birth weight 1302 +/- 164 g) and 6 small for gestational age children (SGA, mean birth weight 1263 +/- 117 g), were studied at the age of 7-12 years, and compared to a group of 26 healthy, age-, sex-, and height-matched children born at term. None of the VLBW children had developed chronic bronchopulmonary disease. Pulmonary function tests and progressive exercise tests on a treadmill were performed. Forced vital capacity, forced expiratory volume at 1 s and forced expiratory flow between 25% and 75% of vital capacity were normal for all subjects. No differences were found in maximum oxygen consumption, anaerobic threshold and maximal heart rate between the AGA and SGA children and the respective controls. Both in the AGA and SGA subgroups, the pre-exercise oxygen uptake results were comparable to those of the controls. In the SGA subgroup the energy cost of running was significantly higher with respect to the controls, while no difference was found between the AGA and the control children. In conclusion, children with birth weight less than 1501 g have normal values of aerobic fitness. In SGA children the efficiency of running is slightly reduced. PMID- 1915483 TI - Spontaneous hyphaema in childhood. AB - Between January 1987 and September 1989 three children presented to the childrens' casualty department with spontaneous hyphaema. Physical examination and haematological investigations were sufficient to determine their cause in two cases (sickle cell disease and acute lymphoblastic leukaemia). In the third child an ophthalmological examination under general anaesthesia revealed a granulomatous lesion of the iris consistent with the diagnosis of juvenile xanthogranuloma. PMID- 1915484 TI - Ultrasonic measurements of the posterior cranial fossa structures in neonates and infants. AB - The structures in the posterior cranial fossa of neonates and infants were visualized ultrasonically via the anterior fontanelle. The diameters of the cerebellar vermis, pons, fourth ventricle and cisterna vermis were measured in the midsagittal plane in neonates (n = 76), 1-month-old infants (n = 61) and 3- to 6-month-old infants (n = 35). The normal values obtained will be useful for evaluation of morphological abnormalities in the posterior cranial fossa. PMID- 1915485 TI - Aseptic meningitis in children: correlation between fever and interferon-gamma level. AB - We studied the correlation between interleukin-1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in cerebrospinal fluid (CSF) and clinical/laboratory findings in children with aseptic meningitis. In 19/27 patients (70%), the CSF IFN level was high at initial diagnosis, and reduced to a low or undetectable level during the convalescent phase (5-14 days later) of the disease. There were no differences in IL-1 beta and TNF-alpha levels between the acute and convalescent phase of the patients. The serum IFN-gamma levels in the patients, which were simultaneously examined were undetectable in the acute phase. When we compared the clinical/laboratory findings between the 29 patients with detectable CSF IFN gamma level and the 21 patients with an undetectable CSF IFN-gamma level in the acute phase, the former demonstrated higher body temperature (P less than 0.01), and higher cell number and protein level in the CSF (P less than 0.05) than the latter. On the other hand, there were no significant differences in the duration of meningeal signs, the titre of C-reactive protein, and the peripheral leucocyte count between the two groups. By the Spearman's rank sum test, the CSF IFN-gamma levels correlated more definitively with the severity of febrile episode (maximal body temperature, duration of fever and body temperature at the first lumbar tap), and the cell number and protein level in the CSF. These results suggest that IFN-gamma produced in the inflamed intrathecal space may be associated with the pathogenesis of aseptic meningitis, especially the production of fever. PMID- 1915486 TI - Epidemiological study of congenital diaphragmatic defects with special reference to aetiology. AB - Congenital diaphragmatic defects (CDD) are easily accessible to ultrasonographic diagnosis. In spite of progress in the management of prenatally detected cases, the mortality rate for CDD remains high. The prognosis depends mainly on the severity of fetal lung hypoplasia but is also linked to the associated malformations. We report on 77 cases of CDD ascertained between 1982 and 1988 from 136,161 consecutive births in the Bouches du Rhone area. The spontaneous perinatal mortality rate was 61% with 28 early post-natal deaths and 14 stillbirths. Eight pregnancies were terminated after prenatal diagnosis. The diaphragmatic defect was associated with other congenital anomalies in 33 cases, more often among stillborn (92.8%) than liveborn infants (23.6%). A chromosomal abnormality was present in 9 cases representing 11.6% of all CDD and in 27.2% of cases with other anomalies. A Mendelian disorder was present in 9 cases (eight Fryns syndrome and one Fraser syndrome). This study underlines the necessity of a systematic work up of prenatally diagnosed cases, including fetal karyotyping and analysis of associated malformations in order to adapt the management of the pregnancy and delivery to the prognosis. PMID- 1915487 TI - Neonatal citrullinaemia with satisfactory mental development. AB - In an infant with neonatal citrullinaemia therapy was instituted on day 1 of life with a low-protein diet and oral supplements of arginine, alpha-keto-acids, essential amino acids and carnitine. The latter may have contributed to the excellent clinical outcome, as evidenced by normal growth and satisfactory psychomotor development at 3 years of age. PMID- 1915488 TI - Patient triggered ventilation in chronically ventilator-dependent infants. AB - Patient triggered ventilation (PTV) has been assessed as a method of respiratory support in infants remaining ventilator-dependent beyond the 1st week of life. Sixteen preterm infants were studied who had a median gestational age of 26 weeks and postnatal age of 22 days. PTV was delivered using a ventilator incorporating an airway pressure trigger. PTV was only successfully maintained until extubation in 3 infants, failing to provide a satisfactory method of respiratory support in the remaining 13 infants after a median of 1 h (range 1-10). One of the 13 infants was persistently asynchronous at 1 h despite manipulation of inflation time. The other 12 infants, at failure of PTV, were making respiratory efforts which were inadequate to consistently trigger the ventilator. Infants in whom PTV was successful were older, more mature and of greater birth weight; the trigger delay at 1 h was significantly shorter in this group (P less than 0.05). A predictor of failure of PTV was asynchrony in the 1st h after commencing PTV (P less than 0.02). We conclude PTV incorporating an airway pressure trigger infrequently provides a useful method of respiratory support in infants who are chronically ventilator-dependent. PMID- 1915489 TI - Detecting vesico-ureteral reflux in asymptomatic siblings of children with reflux by direct radionuclide cystography. AB - The incidence of vesicoureteral reflux (VUR) among asymptomatic siblings of children with VUR is much higher than the estimated incidence in the general population. It might be expected that identifying them and keeping them under close observation and/or either surgical or conservative treatment, might reduce the risk of renal scarring. Fifty-three asymptomatic children, all under 6 years of age and all siblings of children with proven VUR, were studied and direct radionuclide voiding cystography (DRVC). There were 31 (58%) boys, and 22 (42%) girls. Nine children (17%) were younger than 1 year, 13 (25%) were between 1 and 2 years of age, while 31 (58%) were older than 2 years. VUR was detected in 22 (42%) of the 53 siblings. The incidence of VUR varied considerably according to the age, and sex of the child, the highest being in boys younger than 1 year. Most of the severe reflux was seen in children under 2 years of age. Out of 11 patients with VUR, grade 2 and 3, there were 10 younger than 2 years, whereas, only 2 of the 11 siblings with VUR, grade 1 were younger than 2 years of age. The mean age of children with VUR grades 2 and 3 was 19 months, compared to the mean age of 50 months for those with VUR grade 1. DRVC, a highly sensitive method, exposes the patient to much less radiation than X-ray voiding cystography. We believe that the benefit of detecting VUR in asymptomatic siblings with DRVC outweights the invasiveness of the procedure. The predictive value of positive family history alone in identifying VUR in our study was 42%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915490 TI - Cerebral blood flow velocities during orthostasis and physical exercise. AB - The peak flow velocities in the middle cerebral artery were continuously recorded by transcranial Doppler sonography in 29 children. Arterial blood pressure and heart rates were measured every minute. The values observed during orthostasis and physical exercise were compared to baseline values obtained in the supine position. During orthostasis the velocities were, on average, reduced to 87%-94%, the minimal values being 75%-78% of the baseline values. The heart rate increased whereas blood pressure showed only minor alterations. Upon standing up the systolic peak flow velocity remained unchanged while the mean- and enddiastolic peak flow velocities decreased to 66% and 39% respectively. On average, the velocities increased to 103%-108% during physical exercise. Systolic blood pressure increased to the same extent, the heart rate even more. Continuous recording of cerebral blood flow velocities may be more useful than intermittent measurements of blood pressure to differentiate children with and without symptoms of orthostasis. PMID- 1915492 TI - Hans-Ulrich Zellweger (1909-1990). PMID- 1915491 TI - Increased volume density of peripheral mitochondria in skeletal muscle of children with exercise intolerance. AB - Muscle biopsies from 17 children with exercise intolerance and other miscellaneous symptoms and signs showed changes in mitochondrial content. The patients could not be classified according to known criteria. The histopathological changes were quantified by morphometric analysis and the clinical data were statistically analysed to detect intercorrelations. After a mean follow up period of 6.8 years (range 0.5-13.6), patients were re-examined and the course of the disease was determined. No clinical entity could be established. None of the patients showed aggravation of the exercise intolerance, but 71% noted no improvement. An increased volume density of peripheral mitochondria was shown in 59%. Based on clinical history, histopathological changes and course we suggest that some of these patients suffer from a yet unknown disturbance in energy metabolism. Recognition of these patients is important for appropriate counselling. PMID- 1915494 TI - Growth hormone treatment of Turner syndrome patients with insufficient growth hormone response to pharmacological stimulation tests. AB - Growth before and during treatment with biosynthetic human growth hormone (hGH) was studied in 13 patients with Turner syndrome (TS) and a growth hormone (GH) response of less than 10 micrograms/l to two standard provocative tests. During 1 year of treatment with hGH (0.15 IU/kg per day) height velocity (mean +/- SD) increased significantly (P less than 0.001) from 3.7 +/- 1.8 cm/year to 7.6 +/- 1.5 cm/year. The auxological data in these girls before and during treatment with hGH were similar to those observed in TS patients with a normal response of GH to pharmacological stimuli. It is concluded that in girls with Turner syndrome GH testing should only be performed when height velocity is below the Turner norm. In TS patients with residual growth potential a clinically significant growth acceleration can be obtained with a higher-than-replacement dose of hGH, i.e. 0.15 IU/kg per day, regardless of GH testing. PMID- 1915495 TI - Calcitonin secretion in children with insulin-dependent diabetes mellitus. AB - To test the hypothesis that calcitonin (CT) deficiency may contribute to bone mineral loss in insulin-dependent diabetes mellitus (IDDM), we studied basal and calcium stimulated (2 mg/kg body wt. in 5 min) CT levels in 15 children with IDDM and osteopenia. Ten age-sex matched healthy children were studied as controls. Since extractable CT (exCT) allows more sensitive and specific measurement of CT monomer, we measured both total serum CT (tCT) and exCT. Diabetic children had slightly but significantly (P less than 0.05) higher basal levels of both tCT (24.5 +/- 7.1 ng/l) and exCT (5.6 +/- 1.6 ng/l) than controls (tCT: 18.7 +/- 5.4 ng/l; exCT: 4.3 +/- 1.2 ng/l). Calcium stimulation test pointed out significant increase (P less than 0.001) of tCT and exCT in both groups with peak values not significantly different in IDDM in respect to controls. However, diabetic children showed a reduced CT reserve evidenced by a lower peak/basal ratio (diabetics: tCT 1.68, exCT 1.84; controls: tCT 2.49, exCT 2.88) and by a more rapid decrease in CT levels. We conclude that CT deficiency is not a causative factor of diabetic osteopenia. The slightly higher basal CT values suggest that an increased bone reabsorption may be operative in IDDM and it stimulates CT secretion. This chronic "C" cell stimulation may induce the reduction in CT reserve observed employing the calcium infusion test. PMID- 1915497 TI - Persistence of parvovirus B19-DNA in blood of a child with severe combined immunodeficiency associated with chronic pure red cell aplasia. AB - In a female child with severe combined immunodeficiency, pure red cell aplasia was observed which required regular transfusions of erythrocytes. Parvovirus B 19 DNA (but no antibodies) was detected in stored serum samples after the death of the patient. We suggest that the anaemia was a consequence of parvovirus infection which persisted for at least 2 years due to the immunodeficiency. PMID- 1915496 TI - Histiocytic cytophagic panniculitis: report of a case in a 12-year-old girl. AB - We report a 12-year-old girl with nodular skin lesions, fever, pancytopenia, coagulation defects and a fatal outcome within 4 months. Histopathology revealed proliferation of histiocytes with haemophagocytosis in skin, perivisceral fat and haemopoietic organs. The symptoms were most consistent with cytophagic histiocytic panniculitis. PMID- 1915498 TI - AIDS cases in adolescents and young adults in Italy: inferences from descriptive epidemiology. AB - To assess the magnitude of the AIDS epidemic in the Italian adolescent (13-19 years) and young adult (20-24 years) age groups, data on AIDS cases notified to the AIDS Operational Centre as of 31 March 1990 were used. Of the 6068 reported AIDS cases, 0.7% occurred among adolescents and 15.7% among young adults. Among adolescents most cases were haemophiliacs (45.4%), while among young adults, drug use was the most frequently reported mode of transmission (87.5%). Females were more likely than males to contract the disease through the heterosexual contact in both the adolescent (20.0% vs 0%) and in young adult (15.1% vs 0.7%) age groups. Among young adults a geographical trend was present with a decrease in case rates from north to south, while for adolescents the rates were higher in northern and southern than in central Italy. If the incidence of AIDS is to be reduced in Italy, further efforts should be made to target the adolescent age group, since many of the young adult cases are likely to have resulted from HIV infection during adolescence. PMID- 1915493 TI - Pyridoxine-dependent seizures, clinical and therapeutic aspects. AB - Pyridoxine-dependency is a rare autosomal recessive disorder causing a severe seizure disorder of prenatal or neonatal onset, psychomotor retardation and death in untreated patients. Treatment requires life-long supplementation with pyridoxine (vitamin B6). The underlying defect is unknown, and there is no biological marker for the disease. Clinical diagnosis is often delayed and severe neurological sequelae are common. This article summarizes both clinical and therapeutic aspects. PMID- 1915499 TI - Successful bone marrow transplantation and treatment of BCG infection in two patients with severe combined immunodeficiency. AB - We report successful bone marrow transplantation (BMT) in two patients with severe combined immunodeficiency (SCID), who had developed BCG infection following neonatal vaccination. Patient 1 had Omenn Syndrome, associated with hypertrophic non-obstructive cardiomyopathy. Patient 2 had SCID due to adenosine deaminase deficiency. This communication demonstrates that with appropriate anti mycobacterial cover, immunological reconstitution together with full recovery from BCG infection can be achieved by BMT. As demonstrated by persistent negative Mantoux tests, specific cell-mediated immunity to BCG was not acquired following BMT. We suggest that these children may continue to be at risk from mycobacterial infection. PMID- 1915500 TI - Neutrophil chemotaxis in infants delivered by caesarean section. AB - We evaluated polymorphonuclear leucocyte (PMN) chemotaxis and cortisol levels in cord blood from 15 healthy term infants delivered by caesarean section and from 15 healthy vaginally delivered term infants. Mean neutrophil chemotaxis was significantly higher in infants delivered by caesarean section (78.3 +/- 23.4 microns) than in vaginally delivered infants (57.8 +/- 16.6 microns; P = 0.01). Mean blood cortisol level was significantly lower in infants delivered by caesarean section (9.14 +/- 2.76 micrograms/dl) than in infants born by vaginal delivery (20.71 +/- 6.98 P = 0.0001). No relationship was found between PMN chemotaxis and blood cortisol level. The higher neutrophil chemotactic activity observed in infants delivered by caesarean section could be related to general maternal anaesthesia. PMID- 1915501 TI - The cardio-facio-cutaneous syndrome: report of a patient and review of the literature. AB - We report a 3-year-old girl with the cardio-facio-cutaneous (CFC) syndrome. She presented the typical combination of mild developmental delay, postnatal onset short stature with relative macrocephaly, a wide and prominent forehead with posteriorly rotated ears and down-slanting palpebral fissures, an atrial septal defect, and ectodermal abnormalities. All cases reported to date occurred sporadically. The aetiology remains unknown; de novo mutations of an autosomal dominant gene seem the most likely explanation. PMID- 1915502 TI - Maternal phenylketonuria syndrome in cousins caused by mild, unrecognized phenylketonuria in their mothers homozygous for the phenylalanine hydroxylase Arg 261-Gln mutation. AB - Intrauterine growth retardation, microcephaly, and developmental delay in two first cousins lead to the recognition of phenylketonuria (PKU) in their mothers, 24- and 23 year-old sisters with blood phenylalanine concentrations of approx. 1.2 mmol/l who had never been treated and had no overt mental retardation. Both mothers were shown to be homozygous for a point mutation leading to an Arg-to-Gln substitution at codon 261 of the phenylalanine hydroxylase gene, a mutation which has been recently identified and tentatively associated with a mild variant of PKU. Our observation suggests that homozygosity for the Arg-261-Gln mutation can indeed result in "mild" PKU with little or perhaps no mental retardation, but also indicates that in such women, who may go unrecognized if not screened for, blood phenylalanine is elevated enough to cause the maternal PKU syndrome in their offspring. PMID- 1915504 TI - Can high-dose immunoglobulin therapy be indicated in neonatal rhesus haemolysis? A successful case of haemolytic disease due to rhesus (c + E) incompatibility. AB - A male neonate with hyperbilirubinaemia and progressing anaemia due to rhesus (c + E) incompatibility received high dose intravenous gammaglobulin (ivIgG) therapy at 13 days of age. Clinical response to therapy was confirmed by a rapid decrease in serum bilirubin level, and with the prevention of a further decline of the haemoglobin level. No side-effects were noted. High dose ivIgG therapy could be an alternative to (exchange) blood transfusion in case of some haemolytic diseases of newborn. PMID- 1915503 TI - Effects of dopamine infusion on plasma catecholamines in preterm and term newborn infants. AB - Newborn infants (21 preterm and 13 term) received dopamine infusions at a low (2.5-3.4 micrograms/kg per min) and/or high (5-10 micrograms/kg per min) infusion rate and changes in plasma catecholamines were monitored. The mean baseline values for dopamine, noradrenaline and adrenaline were between 240 and 560, 125 and 144 and 62 and 82 pg/ml, respectively. During low-rate infusion of dopamine, there was a significant increase in plasma dopamine (20-100 fold), noradrenaline (three- to five-fold) and adrenaline (threefold). Administration of dopamine at the high rate resulted in an even larger increase in the plasma catecholamines (dopamine, 100-300 fold; noradrenaline, seven- to eightfold; adrenaline, four- to sixfold). In a double-log plot, there was a highly significant correlation between the plasma concentrations of dopamine and noradrenaline (r = 0.77; P less than 0.001). In conclusion, infusion of dopamine in term and preterm newborn infants is accompanied by an enhanced sympatho-adrenal tone which may contribute to the cardiovascular effects of dopamine in these patients. PMID- 1915506 TI - High serum aluminium levels and acute reversible encephalopathy in a 4-year-old boy with acute renal failure. AB - We report a 4-year-old boy, in acute renal failure, who had acute encephalopathy with very high serum aluminium levels (135 micrograms/l [5 mumol/l]) after receiving vesical irrigations with alum. We believe that in situations of non focal neurological deterioration with no apparent cause in patients with impaired renal function receiving aluminium-containing preparations, the possibility of acute aluminium poisoning should be considered. PMID- 1915505 TI - Epoetin alfa in anaemic children or adolescents on regular dialysis. AB - Eighteen patients aged 5-18 years on regular dialysis had a packed cell volume (PCV) less than 0.27. On treatment with epoetin alfa (EA) PCV increased by 0.05 or more in all patients. Iron supplementation was necessary in 13 patients with a ferritinaemia less than 300 micrograms/l before study. During treatment, plasma potassium increased significantly and more vigorous antihypertensive measures were required in 8 patients, 5 of them being already on antihypertensive drugs before EA. Iliofemoral thrombosis occurred in 1 patient 10 days after renal transplant. The data indicate that EA ameliorates the anaemia of chronic renal disease. The main concerns arising during treatment with EA are hyperkalaemia, arterial hypertension and possibly thrombosis. PMID- 1915507 TI - Myopathy in Williams-Beuren syndrome. AB - Williams-Beuren syndrome (WBS) is a disorder of unknown aetiology. The classical features of the syndrome include a typical ('elfin') facies, mental retardation and heart defects. Myopathy has not so far been part of the spectrum of WBS. We studied six patients with WBS aged 3-25 years, five of whom showed clinical and morphological evidence of myopathy. The clinical manifestations of myopathy included hypotonia in infancy, walking delay, joint contractures, scoliosis, and increased exhaustion on exertion. These symptoms were present in variable expression but part of a typical postural pattern. Examination of muscle biopsies showed lipid storage in four patients and increased variability of fibre size in three. In one patient a muscle biopsy gave normal results. Biochemical investigation in four patients with morphological evidence of lipid storage in muscle revealed muscle carnitine deficiency in three. In addition, enzyme activities of fatty acid beta-oxidation were low in one of two specimens tested. It is concluded that a clinically relevant myopathy is part of the multi-system manifestation of WBS and a clinical trial of carnitine supplementation is justified. PMID- 1915508 TI - Colour-flow-mapping in patients with ventricular septal defect. PMID- 1915509 TI - Jubilee Lecture of the Scottish Paediatric Society. Do we really need community paediatricians? A summary of the lecture given at the Triennial Meeting of the Scottish Paediatric Society. AB - To summarise, I have supported the development of a specialty of "child development and rehabilitation" as an independent branch of paediatrics separate from neurology; emphasised the importance of expertise in child abuse for all paediatricians and not just those working in "the community"; described the changing role of specialist paediatric doctors in pre-school surveillance and the school health service; and suggested that we may need community paediatricians with a public health orientation. It is important to determine what community paediatricians should do and to ensure that the training they receive is relevant to the tasks required of them. PMID- 1915511 TI - Paediatric training in the European community. Confederation of European Specialists in Paediatrics (CESP). PMID- 1915510 TI - Osteoarticular infections due to Kingella kingae in children. AB - By the description of two cases of osteoarticular infections due to Kingella kingae in two young children we wish to draw the attention of clinicians to invasive infections due to this micro-organism. Since its biological characterization in 1976, K. kingae has been increasingly reported as a human pathogen. Most common presentations are endocarditis, bacteraemia, septic arthritis, osteomyelitis and spondylodiscitis. Interestingly, osteorticular involvement is largely predominant in previously healthy children. From the literature, we reviewed 51 cases of K. kingae bone and joint infections, representing 23 cases of septic arthritis, 17 of osteomyelitis and 11 spondylodiscitis. Of the cases 88% occurred in children below 5 years of age and in all cases only one bone or joint was involved. An underlying disorder could be found in only 4 patients. Since these infections have a favourable outcome with intravenous antibiotic treatment, proper isolation and identification of K. kingae is essential. PMID- 1915512 TI - The value of the routine chest roentgenogram in the cardiological evaluation of infants and children. A prospective study. AB - The value of the routine chest roentgenogram was studied in 284 patients, newly admitted to our paediatric outpatient department. Emergency patients were excluded from the study. In 141 cases the initial diagnosis after history, physical examination and ECG was "no heart disease", while in 143 cases it was "heart disease". After a follow up of up to 4 years, 170 children appeared to have "no heart disease" and 114 definite heart disease. In 7.7% of cases the chest roentgenogram made at the first visit to the outpatient department led to a change in policy, whereas in only 3.8% was the chest roentgenogram in someway helpful in establishing the correct diagnosis. Amongst those children with initial diagnosis of innocent murmur, the chest roentgenogram led to a diagnosis of "heart disease" in only 2.8% of cases. It is concluded that for the differentiation "heart disease" or "no heart disease", a chest X-ray film is not indicated. In children with "heart disease" the chest X-ray film is also of little value, and is mostly to be used only for documentation. PMID- 1915513 TI - Further delineation of the ichthyosis follicularis, atrichia, and photophobia syndrome. AB - We describe an 18-month-old male infant suffering from the ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome and further delineate the clinical phenotype. Severe retardation of growth and psychomotor development, chill-like seizures, bronchial asthma, urticaria, a proneness to skin infections and transient nail dystrophy observed in our patient are non-obligatory manifestations of this disorder. Histological examination of the atrichia revealed poorly developed, shortened hair follicles and a complete absence of sebaceous glands. The sex ratio of published cases suggests an X-linked recessive inheritance. The marked clinical variability of the IFAP syndrome might be the expression of a contiguous gene defect. PMID- 1915514 TI - Pubertal maturation in girls treated for childhood acute leukaemia. AB - Eleven girls treated during childhood for acute leukaemia were followed up during their pubertal development. At each examination weight, height, pubertal stage, FSH, LH, oestradiol, testosterone, androstenedione and dehydroepiandrosterone sulphate levels were evaluated. Clinical and endocrinological studies were performed according to age and pubertal stage and compared to those of healthy girls matched for age and pubertal stage. Results showed that pubertal maturation and gonadal function were not affected by oncotherapy; however menarche was attained earlier. Early menarche was explained by the overweight of treated girls during early puberty. No evidence of early hypothalamic activation was found, but endocrine patterns showed a faster hypothalamopituitary-ovarian axis maturation in patients than controls. Cranial irradiation showed no correlation with pubertal onset and age at which menarche was attained. Adolescent menstrual and endocrine patterns were normal. PMID- 1915515 TI - The effects of a somatostatin analogue on the metabolism of an infant with Beckwith-Wiedemann syndrome and hyperinsulinaemic hypoglycaemia. AB - Hypoglycaemia is a frequent finding during the neonatal period and may be due to insulin overproduction. Patients with Beckwith-Wiedemann syndrome have reduced numbers of somatostatin-producing cells and decreased extractable somatostatin. In this study the effect of long-acting somatostatin (SMS201-995) on the glucose and insulin levels in an infant with Beckwith-Wiedemann syndrome and hyperinsulinaemic non-ketotic hypoglycaemia is described. SMS201-995 lowered basal insulin levels while maintaining normal glucose and insulin homeostasis. During fasting however, both glucose levels declined rapidly whereas insulin levels did not. The absence of both ketosis and elevated levels of free fatty acids and lactate during hypoglycaemia, as observed in our patient, are important diagnostic clues since the insulin levels themselves may sometimes be only slightly elevated. PMID- 1915516 TI - Disorders of oesophageal motility in children with psychomotor retardation and gastro-oesophageal reflux. AB - A group of 25 children affected by different degrees of psychomotor retardation (severe (n = 13); mild-moderate (n = 12)) and symptoms suggesting gastro oesophageal reflux (GOR) underwent oesophageal manometry and oesophageal pH monitoring. Of these patients, 21 (84%) were affected by GOR. In all children with severe brain damage and GOR (12/13), oesophageal manometry showed marked motility abnormalities that persisted after cure of GOR. In patients with minor retardation and GOR (9/12), oesophageal manometry showed normal motility or a less severe degree of oesophageal motor dysfunction which improved after curing the GOR. These results suggest that oesophageal motor dysfunction is a frequent occurrence in children affected by severe psychomotor retardation and GOR. PMID- 1915517 TI - Salicylate treatment in Kawasaki disease: high dose or low dose? AB - Salicylate is the basic therapy for Kawasaki disease, however its optimal dose is controversial. We investigated the therapeutic efficacy of high dose (100 mg/kg per day, n = 30) versus low dose (30 mg/kg per day, n = 30) salicylate. Duration of fever, SGPT, serum salicylate, plasma thromboxane B2 (TxB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) levels were compared before enrollment and on days 4, 7 and 14 of treatment. In the high dose group, duration of fever was significantly shorter than that of the low dose group (3.2 +/- 0.3 versus 5.4 +/- 0.8 days, P less than 0.05), however, SGPT levels were significantly elevated (157 +/- 34 versus 48 +/- 11 IU/1, P less than 0.05). No differences in the incidence of coronary artery lesions were observed (5/30 versus 7/30). Plasma TxB2 production was completely blocked in both groups, and plasma 6-keto-PGF1 alpha levels in the high dose group on day 14 was lower than that in the low dose group (39 +/- 8 versus 159 +/- 65 pg/ml, P less than 0.05). SGPT and plasma 6 keto-PGF1 alpha correlated with serum salicylate concentration. These data suggest that high dose salicylate therapy may be disadvantageous as anti thrombotic therapy, and supports the notion that low dose therapy is safe in the acute stage of Kawasaki disease. PMID- 1915518 TI - Defective activation of the alternative pathway of complement in patients with homozygous C2 deficiency: studies in two unrelated families. AB - Selective homozygous deficiency of the second component of complement, C2, with increased susceptibility to infection was detected in five children of two unrelated families. Because the haemolytic activity of the alternative complement pathway (AP) was in the low normal range, we evaluated the AP activation pattern. Serum levels of factor B measured immunochemically and the haemolytic function of factor B were low normal. Levels of C3d were not increased. Activation products of factor B were undetectable indicating the absence of in vivo activation of AP. Activation of C3 in vitro by activators of the AP (zymosan A and lipopolysaccharide) was profoundly deficient in homozygous C2 deficiency while heterozygous carriers exhibited intermediate values. There was no correlation between serum levels of factor B and in vitro C3 activation. We conclude that defective AP activation may contribute to increased susceptibility to bacterial infections in some patients with homozygous C2 deficiency. PMID- 1915519 TI - Chronic bilateral dacryo-adenitis in identical twins: a possible incomplete form of Sjogren syndrome. AB - We report an unusual case of chronic bilateral dacryo-adenitis in 10-year-old identical twin sisters. Both girls presented with bilateral lacrimal gland enlargement and developed moderate xerophthalmia and keratitis. Both the lacrimal and minor salivary gland biopsies showed a non-granulomatous inflammatory infiltration of mono-nuclear cells. All granulomatous diseases and neoplasms could therefore be ruled out and only Sjogren syndrome and very few other forms of chronic dacryo-adenitis remained as possible diagnoses. Both patients and their parents were evaluated for auto-antibodies. Very low titres of smooth muscle antibodies were found in one, antinuclear antibodies in two and anti-dsDNA antibodies in all four members of the family. Even though the titres of antinuclear and anti-dsDNA antibodies increased in one of the sisters, both patients did not develop any sign or symptom of a systemic connective tissue disease. During the 6 years' follow up, both patients showed persistent tarsal gland enlargement but no other symptoms apart from a moderate xerophthalmia and occasional mild keratitis. PMID- 1915521 TI - Phenylketonuria does not cause cataracts. AB - In a study of 46 adults aged 28-71 years with untreated phenylketonuria (PKU) there were 3 (6.5%) with cataracts. This incidence was similar to that in the Australian population and in a control series of intellectually disabled adults. Only two of the PKU patients with cataracts could be examined by slit-lamp biomicroscopy and in both the findings suggested that the prolonged use of phenothiazines may have played a role. Slit-lamp examination of a further ten untreated PKU patients and 13 PKU adults who had been treated in childhood revealed only small lens opacities (in 40%) of a type found in 72.7% of a control group. The study provides no support for claims that PKU can cause cataracts. PMID- 1915520 TI - A family with severe X-linked arthrogryposis. AB - Five males are reported with severe X-linked arthrogryposis. Main findings are marked respiratory insufficiency and feeding problems, multiple contractures, deformities of chest and vertebral column, and typical facies. Most of these findings can be explained by a pronounced prenatal and postnatal muscle weakness. The sole living child has severe psychomotor retardation. Several female carriers show mild features (clubfeet, contractures, hyperkyphosis, and slight muscle weakness). One manifesting carrier is affected more severely (multiple contractures, mental retardation, and various dysmorphic features). Additional investigations including muscle biopsy revealed none of the usual signs of denervation, and pointed to the presence of a degenerative muscle disorder. PMID- 1915522 TI - Chronic metabolic alkalosis in an infant with cystic fibrosis. AB - A 6-month-old infant suffering from cystic fibrosis is reported. In spite of an apparently appropriate treatment and in absence of respiratory infection, the patient showed progressive anorexia, intermittent vomiting and weight loss. These non-specific signs and symptoms could all be explained by metabolic alkalosis and disappeared immediately after oral supplementation with sodium and potassium chloride. This unusual metabolic complication should be searched for in every cystic fibrosis infant with unexplained anorexia and failure to thrive. PMID- 1915523 TI - High frequency oscillatory ventilation near resonant frequency of the respiratory system in rabbits with normal and surfactant depleted lungs. AB - It has been suggested that high frequency oscillatory ventilation (HFV) might improve gas exchange and reduce the risk of pressure-related side-effects compared to conventional mechanical ventilation (CMV). Whereas most studies have used arbitrarily set frequencies for HFV, we evaluated the effects of HFV near resonant frequency (fr). Anaesthetised and tracheotomized adult rabbits (n = 10; 3.8-5.1 kg body weight) were ventilated by alternating periods of CMV and HFV near fr. Negative ventilator resistance was used for complete resistive unloading of the respiratory system before each HFV period. This enabled a continuous swinging at resonance thus allowing measurement of fr and selection of exactly that frequency for the HFV run. Intra-animal CMV-HFV comparisons (n = 4) were performed on each animal: with healthy lungs at a mean airway pressure (MAP) of 0.5 kPa and after saline lung lavage at MAPs of less than 1.5 kPa; 1.5-1.8 kPa; greater than 1.8 kPa. Surfactant removal caused total respiratory system compliance (Ctot) to decrease from 44 +/- 5 to 22 +/- 3 ml/kPa. Corresponding fr was 244 +/- 48 and 360 +/- 30 min-1, respectively. HFV produced effective pulmonary gas exchange but did not improve arterial oxygenation in comparison with CMV at matched MAPs both before and after surfactant depletion. Volume amplitudes of oscillation necessary to achieve normocapnia were slightly above the natural plus equipment (2 ml) dead space. Maximum intra-alveolar pressure (Pmax) was calculated for the HFV runs from MAP, Ctot, and the volume amplitude of oscillation. Pmax during CMV was nearly twice that during HFV at equivalent PaCO2 and equivalent MAPs throughout the experiments. PMID- 1915524 TI - Testosterone esters advance skeletal maturation more than growth in short boys with chronic renal failure and delayed puberty. AB - Four young males with chronic renal failure and absent or stagnant puberty were treated with testosterone esters. Endocrine evaluation before therapy showed low plasma follicle stimulating hormone (FSH) levels and relatively high luteinizing hormone (LH). Following therapy skeletal maturation accelerated more than growth velocity, resulting in a lower predicted adult height. In three patients osteoporosis increased or rickets developed. Testosterone therapy was effective in developing sex characteristics, but endogenous pubertal development was not stimulated. Growth velocity was increased, but the effect on growth was more than outweighed by bone age acceleration. PMID- 1915525 TI - High dose intravenous gamma-globulin in intractable epilepsy of childhood. AB - Eight children aged between 1.3 and 13 years suffering from epilepsy refractory to conventional anticonvulsive therapy were treated with high dose intravenous gamma globulin (200 mg/kg, 3 times per week, repeated after 3 weeks). Immunological studies after therapy showed normal results. In four children, clinical and EEG findings markedly improved. In one other case a partial response was noted. No improvement was observed in the remaining three cases. We confirm that although the mechanism is still obscure, high doses of i.v. gammaglobulin may have a beneficial effect in a significant number of children with intractable epilepsy. PMID- 1915526 TI - Organic aciduria in Pearson syndrome. PMID- 1915527 TI - Episiotomy and neonatal lidocaine intoxication. PMID- 1915528 TI - Isolated intention tremor: a sign of metastatic neuroblastoma. PMID- 1915529 TI - Coffin-Siris syndrome with normal plasma biotinidase activity. PMID- 1915531 TI - Functional, augmented rectal bladder: early clinical experience. AB - From August 1988 until March 1990, 10 female patients received an augmented, functional rectal bladder according to the technique first described by Kock. Indications were radical cystectomy in 8 and undiversion from a previously wet stoma in 2 patients. There was no perioperative mortality. Postoperative complications were: one obstructive pyelonephritis (treated with a temporary nephrostomy); one obstruction at the ileal intussusception (operative revision), and one slipping at the sigma nippel (no treatment). Intravenous pyelographies taken 2-3 months postoperatively, showed 13 normal and 5 slightly dilated renal units. All patients are completely continent by day, 7 are continent at night, 2 wear sanitary pads during the night due to occasional spotting. The preliminary experience with this new technique is encouraging and warrants further clinical application in patients in whom the external urethral sphincter is not available as continence organ. PMID- 1915530 TI - First experience with pentamidine inhalation in human immunodeficiency virus infected children. PMID- 1915532 TI - Prognostic factors in prostatic adenocarcinoma assessed by means of quantitative histology. AB - A series of 91 patients with prostatic adenocarcinoma were retrospectively followed up for an average of 15.6 years. The biopsies of the primary tumours were analysed using morphometry for six nuclear features, mitotic-activity index (MAI) and volume-corrected mitotic index. The histological grading of the tumours into three grades was done, and perineural infiltration and lymphatic infiltration were estimated. Clinical stage (p = 0.0137), lymphatic infiltration (p = 0.076) and histological grade (p = 0.1603) were the best predictors of survival in univariate analysis. A multiparameter analysis of progression in T category disclosed the MAI to be the most important single prognostic factor (p = 0.0276). Histological grade predicted progression in M category (p = 0.0166) in the same analysis. In intracapsular T1-T2 tumours, the SD of nuclear perimeter (p = 0.008) was shown by a multivariate analysis to be the most important predictor of progression. Progressed T1-T2 tumours had higher mitotic index values (p = 0.0215). The results advocate the use of mitotic indexes and morphometric measurements instead or as an adjunct of the conventional histological grading while predicting the progression of prostatic adenocarcinoma. PMID- 1915533 TI - Radical prostatectomy for carcinoma of the prostate: long-term follow-up of 115 patients. AB - From July 1969 to September 1990, 370 patients with prostatic cancer underwent radical prostatectomy at our institution. Of these 370 patients, 115 consecutive patients could be followed for more than 10 years (mean 12.5). Patients with stage pT1-pT3 tumors received no further treatment until progression occurred. Patients with regional lymph node metastases (stages pT2-3pN1-2M0) were treated by either an immediate orchiectomy or an adjuvant hormonal therapy. No radiotherapy was applied prior to radical prostatectomy or thereafter. Of the 115 patients followed for more than 10 years, 84 had stage pT1-2, 22 had stage pT3, and 9 had stage pT2-3pN1-2 tumors. The observed 10-year survival rate of all 115 patients (including those with regional lymph node metastases) was found to be 67.0%. The 10-year disease-free survival rate was 58.3% and the tumor-related survival rate was 83.5%. Considering only patients with locally confined (stage pT1-2) tumors, the 10-year survival rate was 75.0%. This observed survival rate equals the 10-year survival expectancy of a male age-matched control population (69.9%). Progression (local recurrence or distant metastatic spread) was noted in 27.8% of patients within the 10-year interval after radical prostatectomy. Within this time interval, 16.5% of the patients died from their disease. PMID- 1915534 TI - Renal cell carcinoma: vena caval invasion and prognostic factors. AB - Ninety-one consecutive patients with renal cell carcinoma stages pT1-4/N0-3/V0 2/M0 were analyzed for survival rates. The overall 5-year survival was 57%. Factors which made an impact on 5-year survival rates were: (1) grade of anaplasia (GI: 72%, GII: 42%, GIII: 22%; p = 0.0001); (2) pathological stage (pT1 2: 86%, pT3: 30%; p = 0.0000); (3) perinephric fat invasion (pT1-2: 86%, pT3a: 61%; p = 0.01); (4) nodal involvement (N0: 69%, N1: 11%; p = 0.0000), and (5) venous invasion (V0: 72%, V1-2: 30%; p less than 0.01). There were no differences in survival rates between V1 and V2 tumors (p greater than 0.05). Using multivariate statistical analysis we found that grade of anaplasia and venous invasion contained dire prognostic information (p = 0.0000). Among patients with stage pT3b, those without perinephric fat invasion or nodal involvement had a better survival rate than those with capsular infiltration (p less than 0.01) and a significantly better rate than those with perinephric fat invasion and nodal involvement (p less than 0.01). Moreover, there were no differences between stages pT3b with venous invasion only and stages pT1-2 (p greater than 0.05). Patients with venous invasion developed distant metastases with a significantly higher frequency than those without (p = 0.01). The prognostic impact of venous invasion is unclear yet, but is probably related to perinephric fat invasion and nodal involvement. Until further data are collected, the radical approach with complete removal of the thrombus remains the treatment of choice for localized renal cell carcinoma with vena caval extension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915535 TI - Endoscopic treatment of vesicoureteral reflux following transurethral resection of a vesical carcinoma by Teflon injection. AB - We have treated 33 patients who presented with reflux in 40 ureters following transurethral resection (TUR) for bladder cancer. One or two injections of Teflon were made under the submucosal intramural ureter. Among the 32 ureters that could be correctly evaluated, we observed that vesicoureteral reflux disappeared in 18 (56.3%), and decreased the grade of reflux in 5 (15.6%). There were no modifications in the 9 remaining ureteral units (28.1%). Control urogram and/or sonogram scan were performed in all cases and demonstrating the absence of obstructive uropathy. PMID- 1915536 TI - Ostioplasty: a simple technique for ureterovesical reconstruction following intravesical ureterocelectomy. AB - A simple operation for the management of simple, i.e. intravesical, ureteroceles, which we have named 'ostioplasty', is presented. After unroofing the ureterocele, the retracted, gaping ureteric ostium is advanced and fixed medially to the center of the bladder trigone with three 5-0 polyglycolic acid sutures. The exposed intravesical ureter is covered with a new mucosal layer formed from the mobilized lateral edges of the unroofed ureterocele, sutured together over the ureter with 5-0 polyglycolic acid. Ostioplasty has been used in 5 patients so far with excellent anatomic and functional results. It is a simple and valuable surgical option to standard ureterovesical reimplantation after excision of a simple ureterocele, provided that the ureterocele is of moderate size and the bladder trigone retains good muscular support. PMID- 1915537 TI - Transitional cell carcinoma of the bladder or renal pelvis in children. AB - Transitional cell carcinoma (TCC) of the bladder or renal pelvis is rare in children. We report 2 children with TCC of the bladder and 1 with TCC of the renal pelvis. One of the two children with bladder carcinoma experienced frequent intravesical recurrences, which is in contrast to the usual clinical course of bladder carcinoma in children. In the 3rd child, renal pelvic carcinoma was found incidentally in a renal pelvis specimen removed during pyeloplasty. PMID- 1915538 TI - Urinary Tamm-Horsfall protein excretion in patients with primary vesicoureteral reflux. AB - The excretion of urinary Tamm-Horsefall protein (THP) was determined by enzyme linked immunosorbent assay and glomerular filtration rate (GFR) was calculated with technetium-99m diethylenetriamine pentacetic acid (99mTc-DTPA) renal scintigraphy in 26 consecutive patients with primary vesicoureteral reflux (VUR) before and after antireflux surgery. Wide variations of urinary THP excretion and GFR were seen in all grades of VUR. On the basis of the relationship between urinary THP excretion and GFR before the surgery, patients were divided into three groups. The first group (group A, n = 8) had normal urinary THP values and normal values of GFR. The second group (group B, n = 11) had high THP excretion and moderately decreased GFR, the third group (group C, n = 7) had normal urinary THP excretion and severely decreased GFR. In group A, urinary THP values remained normal and GFR improved in all patients after surgery. In group B, GFR improved when urinary THP dropped immediately, but GFR did not improve when urinary THP remained high after surgery. In group C, GFR did not improve and urinary THP continued to be low or tended to drop again after the surgery. The results suggested that serial measurements of urinary THP excretion and GFR by 99mTc-DTPA renal scintigraphy before and after antireflux surgery are useful for the evaluation of renal function in patients with primary VUR. PMID- 1915539 TI - Effect of distilled water and bacillus Calmette-Guerin on exfoliated bladder tumor cells. AB - The effect of distilled water on exfoliated tumor cells from transitional bladder carcinoma was compared to the effect of bacillus Calmette-Guerin (BCG; a nonspecific immunotherapeutic agent) dissolved in either saline or distilled water. The experiment was controlled by comparison to the effect of saline on tumor cells under the same conditions. Distilled water proved as effective as BCG in distilled water (p less than 0.001) and much more destructive than BCG in saline within the 2-hour time limit of the experiment (p less than 0.001). PMID- 1915540 TI - Ultrastructural changes of bladder cancer cells following methylene blue sensitized photodynamic treatment. AB - The cytotoxic efficacy of methylene blue-sensitized photoinactivation of bladder cancer cells has been proved in vitro and in vivo in our previous work. The ultrastructural changes of MBT-2 murine bladder cancer cells following methylene blue-sensitized phototherapy have been evaluated by scanning and transmission electron microscopy. MBT-2 cells were pretreated with 0.1% methylene blue, and then exposed to ordinary light for different durations from 1 to 60 min. Both electron microscopic examinations showed that changes in tumor cells occurred at 5 min of illumination with fenestration and minipore formation on the cell membrane and mitochondrial disintegration. At 30 min, cleavage and cracking of the cell membrane with ribosomal lysis were noted. Finally, fragmentation with decomposition of the membrane and chromosomal condensation and lysis resulted at 60 min. This study showed that the cytotoxic effect induced by methylene blue phototherapy is initiated in the cell membrane and intracellular mitochondria in the early phase. PMID- 1915541 TI - Relationship between DNA flow cytometric data, nuclear morphometric variables and volume-corrected mitotic index in transitional cell bladder tumors. AB - The relationship between the mean nuclear area, standard deviation of the nuclear area, the mean area of the 10 largest nuclei in a section (NA10), volume corrected mitotic index (M/V index), DNA index (DI) and S-phase fraction (SPF) were assessed in a panel of 222 transitional cell bladder tumors. The relations between the morphometric variables and DI (p less than 0.0001), and between the morphometric variables and SPF (p less than 0.0001) were highly significant. Pearson's correlation coefficients between NA10 and DI (r = 0.413) and between SPF and the M/V index (r = 0.536) were also highly significant (p less than 0.0001). The SPF could be estimated reliably by morphometric methods, whereas the estimation of DI is not perfect. The combination of morphometric variables allowed a more reliable estimation of flow cytometric parameters. The results suggest that DI and SPF can be semiquantitatively estimated in routine histopathological sections by simple morphometric methods. PMID- 1915542 TI - Serum immunosuppressive acidic protein as a tumor marker for renal cell carcinoma. AB - Since there are no reliable tumor markers in renal cell carcinoma, the present study was undertaken to evaluate immunosuppressive acidic protein (IAP) in patients with this tumor. Serum IAP levels were measured in 143 consecutive patients before and/or after nephrectomy by turbidimetric immunoassay. IAP levels had increased according to tumor diameter. Positivity rates of IAP were noticed as 45%, 75%, and 100% for patients with stage I/II, stage III, and stage IV diseases, respectively. Three-year survival rates also correlated with IAP: 96%, 81%, and 44% in preoperative levels below 500, of 501-1,000, and of more than 1,001 micrograms/ml, respectively. Serum IAP levels decreased within 3 months after the operation and increased with recurrence. These results suggest that serum IAP may serve as a tumor marker in patients with renal cell carcinoma. PMID- 1915544 TI - An unusual scrotal swelling: epididymal malakoplakia. A case report and review of literature. AB - A case of malakoplakia confined to the epididymis is described. This patient presented with an incidental epididymal swelling during exploration of an irreducible inguinal hernia. The clinical features are compared with those of the previously reported cases. PMID- 1915543 TI - Actinomycosis of urachal remnants. AB - A case of actinomycosis of the urachus is described. A 25-year-old woman presented with a midline mass below the umbilicus. The differential diagnosis included an inflammatory or a neoplastic lesion. Diagnosis was made by histologic examination, after complete excision of the tumour. Post-operative penicillin was given and the patient's recovery was uneventful. A review of the literature is presented with special reference to the pathogenesis and treatment. PMID- 1915545 TI - Renal extramedullary hematopoiesis simulating hypernephroma. AB - We report a 63-year-old woman who presented with anemia and a left kidney mass. Guided fine-needle aspiration of the mass revealed extramedullary hematopoiesis and enabled avoiding an unnecessary operation. Subsequent bone marrow biopsy demonstrated myelofibrosis. Twenty-four months later the mass remained stable. PMID- 1915546 TI - Effect of estrogen and androgen hormones on the prostate transplanted under the kidney capsule of mice. PMID- 1915548 TI - Interleukin 6 inhibits delayed-type hypersensitivity and the development of adjuvant arthritis. AB - We studied the effect of interleukin 6 (IL 6) on the delayed-type hypersensitivity (DTH). In mice immunized with sheep red blood cells (SRBC), a DTH response was evoked by antigen challenge into the hind paw 5 days after immunization. The magnitude of the response was assessed by footpad swelling measured 24 h after antigen challenge. IL 6 significantly suppressed the DTH in its induction phase in a dose-dependent manner when administered s.c. into the back at a dose of greater than 2.5 micrograms twice a day (5 micrograms/day) for 5 consecutive days from the day of immunization (day 0) to 1 day before antigen challenge (day 4). Heat-inactivated IL 6 did not suppress the DTH response. Furthermore, the suppressive activity of IL 6 was completely abolished by affinity chromatography on an anti-IL 6 antibody. This suppression was also obtained when IL 6 was administered only on day 0 and day 1, but not on days 3 and 4. This indicates that IL 6 acts on the early part of the induction phase of DTH development. Furthermore, footpad swelling was suppressed even by the administration of IL 6 after antigen challenge. These results show that IL 6 suppresses both the induction and effector phases of DTH. To confirm further this inhibitory effect of IL 6, we examined its effect on the development of adjuvant arthritis in rats. Administration of IL 6 also significantly suppressed the development of adjuvant arthritis. PMID- 1915547 TI - Differential inhibition of interleukin 2- and interleukin 4-mediated human B cell proliferation by ionomycin: a possible regulatory role for apoptosis. AB - Surface immunoglobulin (Ig) cross-linking by anti-IgM (mu) antibodies leads to B cell activation resulting in numerous early biochemical events including an increase in intracellular [Ca2+]. Furthermore, anti-mu-activated B cells become able to proliferate in response to interleukin (IL)2 and IL4. These studies examined the effect of the calcium ionophore ionomycin, an enhancer of cytoplasmic [Ca2+] levels, on IL2 and IL4-mediated proliferation of anti-mu stimulated normal human B cells. Ionomycin inhibited the proliferative response of anti-mu-activated B cells to IL4. In contrast, IL2 and phorbol 12,13 dibutyrate (PBu2)-mediated B cell proliferation was refractory to the growth inhibitory effects of ionomycin. In an attempt to delineate a possible mechanism(s) for this differential growth effect of ionomycin, we first studied direct effects of ionomycin on activated B cells. Our data suggested that ionomycin induced DNA fragmentation in anti-mu-costimulated B cells. Interestingly, in contrast to PBu2, IL4 did not prevent ionomycin-dependent DNA fragmentation. Importantly, H7, an inhibitor of protein kinase C activation, down regulated only the IL2 and PBu2-driven B cell proliferation but not B cell proliferative response to IL4. These results suggest that putative protein kinase C activation, either by direct treatment with phorbol ester or during IL2 signaling, counteracts the inhibitory effects of ionomycin. In contrast, IL4 signaling does not exhibit the same protective properties. PMID- 1915549 TI - Diversity of immunoglobulin heavy chain gene segment rearrangement in B lymphoblastoid cell lines from X-linked agammaglobulinemia patients. AB - X-linked agammaglobulinemia (XLA) is characterized by an arrest in early B lymphocyte differentiation. Precursor B cells are present in the bone marrow (BM), whereas peripheral blood B cell numbers are severely decreased. A series of Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines (BLCL) was established from peripheral blood of three XLA patients belonging to one pedigree. These BLCL manifested productive VHDJH rearrangements and a random utilization of the VH families. The CDR3 regions of the rearrangements varied in length from 12 to 47 nucleotides and included N regions in all cases. The results supported the conclusion that the few B lymphocytes in peripheral blood of XLA patients exhibit all mechanisms that generate immunoglobulin (Ig) heavy (H) chain diversity. However, no evidence for somatic mutation was found. Within the VH3 family 50% of the expressed VH gene segments belonged to a single subgroup and within the VH4 family a preferential utilization of one VH4 gene element was observed. The utilization of H chain joining (HH) elements was biased to JH4 and JH6 and a high percentage of the CDR3 regions was found to be generated by unconventional mechanisms, such as multiple D usage and the fusion of D elements to D segments with irregular recombination recognition signals. These unique features of the recombined and expressed VHDJH regions in XLA may explain the inability of XLA patients to respond to a variety of antigens. Alternatively, they could be secondary to a B lymphocyte maturation defect in XLA. PMID- 1915550 TI - The B cell antigen receptor of class IgD can be expressed on the cell surface in two different forms. AB - Membrane-bound immunoglobulins of the IgM and IgD class are expressed on the B cell surface in association with a disulfide-linked heterodimer consisting of alpha and beta subunits. While the alpha component of the IgM antigen receptor (IgM-alpha, 34 kDa) is encoded by the B cell-specific gene mb-1, the gene coding for IgD-alpha (35 kDa) has not yet been identified. We show here that the alpha component of the IgD antigen receptor is also encoded by the mb-1 gene. The difference in molecular weight between IgM-alpha and IgD-alpha thus seems to be due to post-translational modifications of the mb-1 gene product. We also demonstrate that the previously described myeloma variant J558L delta m2.6 expresses an alternative form of the IgD antigen receptor, which does not contain an alpha/beta heterodimer. PMID- 1915551 TI - Chimeric mouse human IgG3 antibodies with an IgG4-like hinge region induce complement-mediated lysis more efficiently than IgG3 with normal hinge. AB - We have altered the amino acid sequence of the hinge and the first constant domain (CH1) of mouse/human chimeric IgG3 antibodies by site-directed mutagenesis, so as to make the sequences identical to those of IgG4. All the mutant antibodies with altered hinge region were more active in complement activation and complement-mediated lysis than native IgG3. The mutations in CH1, however, did not alter the activity. This demonstrates the importance of the hinge region in modulating this effector function. The results show that the primary structure of neither CH1 nor the hinge of IgG4 is responsible for the lack of complement activation shown by this subclass. PMID- 1915552 TI - A rearranged lambda 2 light gene chain retards but does not exclude kappa and lambda 1 expression. AB - Mice transgenic for the lambda 2 light chain of MOPC315 were established. In newborn transgenics (TG), lambda 2 was the only light chain found on B cells. However, by day 21, lambda 2 high kappa low as well as lambda 2 low kappa high double expresser populations were emerging. lambda 2 was found on an increased fraction of serum immunoglobulins (Ig), this fraction declined with age. Correspondingly, kappa and lambda 1 expression was suppressed in young mice but increased with age. In adult mice kappa or lambda 1 were often co-expressed with lambda 2 in single serum Ig molecules. Most B cell hybridomas from and adult TG secreted lambda 2,kappa mixed molecules and had rearranged their kappa chain genes. One lambda 2,lambda 1 hybridoma and even a lambda 2,kappa,lambda 1 hybridoma were also found. In conclusion, isotypic exclusion in lambda 2 TG is complete in newborns but becomes increasingly leaky with age. Antigen probably expands the lambda 2 low kappa high B cell population; this population is most likely the major source of serum Ig in adult lambda 2 TG mice. In contrast, the lambda 2 high kappa low population, a major fraction of which is CD5+ Mu low delta low, appears only infrequently to develop into antibody-secreting plasma cells. PMID- 1915553 TI - Experimental Borrelia burgdorferi infection in inbred mouse strains: antibody response and association of H-2 genes with resistance and susceptibility to development of arthritis. AB - We have investigated the specific humoral immune response and its correlation to the development of disease after experimental inoculation of B. burgdorferi in different inbred strains of mice. All mouse strains tested showed high levels of specific IgM antibodies during the initial 10 days of infection. Specific IgG antibodies predominantly of the IgG2a, IgG2b and IgG3 isotypes were found in increasing amounts by 14 days post infection. Antibody titers peaked at days 65 and 110. Particularly low titers of specific IgM and/or IgG antibodies were detected in sera of AKR/N and B10.BR mice. Antibodies specific for numerous B. burgdorferi antigens including the outer surface proteins A (31 kDa) and B (34 kDa) and a protein(s) of molecular mass of approximately 40 kDa, most probably 41 kDa (flagellin) and/or 39 kDa (p39), were induced in all inbred mouse strains within 2 weeks inoculation albeit in varying concentrations. Later during infection, the patterns of antibody specificities were much more complex. With regard to development of disease all strains of mice tested fall into three groups: (a) mice of H-2k haplotype (AKR/N, C3H/HeJ, C3H/HeN, B10.BR) developed a chronic progressive arthritis in the tibiotarsal joints, (b) mice of H-2 haplotypes, H-2b (C57BL/6), H-2j (B10.WB), H-2r (B10.R111) and H-2s (B10.S) developed arthritis of variable duration and intensity which was not progressive and (c) mice of H-2d haplotype (BALB/c, DBA/2, C.B-17, B10.D2, Cal.20), irrespective of their background genes or Igh allotype, showed no clinical signs of arthritis at any time point following inoculation of B. burgdorferi organisms. The finding of similar patterns of apparently protective antibodies in all mouse strains tested together with the striking association between the H-2d haplotype and resistance, and between the H-2k haplotype and the occurrence of B. burgdorferi-induced arthritis suggest a critical role of T cells in the development of the disease in mice. PMID- 1915554 TI - Bidirectional activating signals between Trypanosoma brucei and CD8+ T cells: a trypanosome-released factor triggers interferon-gamma production that stimulates parasite growth. AB - The hemoflagellate Trypanosoma brucei (T.b.) is the cause of African sleeping sickness. T. b. brucei which is pathogenic for rodents but nonpathogenic for humans was used to examine the interactions between the parasite and mononuclear cells (MNC). Co-cultivation in vitro of rat or human MNC and T.b. brucei resulted in a rapid non-antigen-specific release of interferon-gamma (IFN-gamma) which was dependent on CD8+ lymphoid cells. The parasites triggered MNC proliferation if IFN-gamma was blocked by a specific antibody in vitro. Separate cultures of parasites and MNC in a two-chamber system allowing exchange of soluble mediators showed CD8+ cell-dependent MNC triggering, indicating that a diffusable factor released by trypanosomes acts on the MNC. Gel filtration according to molecular mass of disrupted parasites and assay of the fractions revealed a peak activity at an approximate molecular mass of 185 kDa for the trypanosome-derived lymphocyte-triggering factor (TLTF). Conversely, there was a CD8+ cell-dependent action of MNC on the trypanosomes. MNC released a diffusable factor that in short term experiments caused a striking increase in number of parasites. This effect was inhibited by antibodies against rat IFN-gamma. The increase in number of trypanosomes was promoted by rat MNC or rat IFN-gamma but not human MNC or human IFN-gamma suggesting a species-restricted recognition of IFN-gamma. An in vivo uptake of IFN-gamma by the parasites was suggested by immunohistochemical staining of T.b. brucei with an mAb against rat IFN-gamma and Western blot of the parasites showing a band with a molecular mass corresponding to IFN-gamma. The bidirectional signals we define here may explain certain features of trypanosomiasis, i.e. T cell activation, immunosuppression and host-range restriction. The seemingly important role of the TLTF indicates that it should be purified and explored as target for immune-specific intervention. PMID- 1915555 TI - CD4 and CD8 accessory molecules function through interactions with major histocompatibility complex molecules which are not directly associated with the T cell receptor-antigen complex. AB - Both the subset-specific, CD4 and CD8 T cell accessory molecules and the antigen specific T cell receptor (TcR) interact with major histocompatibility complex (MHC) class I and class II molecules on the surface of antigen-presenting cells. We analyzed whether the CD4/CD8 molecules exert their accessory function through binding with the same MHC molecules which participate in the TcR-antigen-MHC complex. We utilized a CD4-, CD8-, class I-allospecific T cell hybridoma which functionally manifests both cytotoxic T lymphocyte (CTL) and T helper1 (Th1) phenotypes, and rendered it bispecific by transfecting it with genes encoding either a class II-restricted, 2,4,6-trinitrophenyl (TNP)-I-Ad-specific TcR or a non-MHC-restricted chimeric TcR, composed of a variable part of an anti-TNP antibody. Expression of either CD4 or CD8 transgenes in these hybridomas enhanced and augmented their reactivity towards the appropriate target cells regardless of the type of TcR-MHC interaction. Thus, class I-specific responses could be enhanced through CD4-class II interactions, and class II-restricted responses could be augmented through CD8-class I interactions. Furthermore, these accessory molecules also potentiated TNP-specific responses by the chimeric TcR which is MHC unrestricted. The accessory molecules facilitated both interleukin 2 (IL2) production and cytolytic activity by shortening the activation time and rendering the cells responsive to lower antigenic stimuli. The degree of activity of the T cell hybridomas correlated with the level of accessory molecule expression and was not related to the effector function mediated by the cells. Anti-CD4 or -CD8 antibodies completely inhibited the activity of transfectants expressing the corresponding accessory molecule, regardless of the MHC type of the TcR interaction. Such antibodies blocked direct TcR stimulation provided by either anti-T3/Ti antibodies or lectins, but could not inhibit the activation through agents that bypass the TcR such as phorbol 12-myristate 13-acetate plus ionophore. Taken together, these studies demonstrate that the CD8/CD4 molecules can exert their accessory function through interactions with MHC molecules which are not directly associated with the TcR-Ag-MHC complex, and that this accessory effect is associated with TcR-mediated triggering at an early stage of the signaling process and is not related to the effector mechanism assigned to the CD4 and CD8 T cell subsets. PMID- 1915556 TI - Is there really a "lack of natural tolerance to allotypic gamma-globulins in rabbits"? AB - We present data of extended studies on the possibility of maternally derived allotype Ig inducing a state of natural immunological tolerance to a non inherited allotype in the offspring. Rabbits homozygous at the a locus, encoding allotypes in the variable region of immunoglobulin heavy chains, and rabbits homozygous at the unliked b locus, encoding allotypes of the constant region of kappa 1 chains, were immunized at the age of 2 months against the non-inherited allotype of their heterozygous mothers to which they had been exposed in utero and in early life. As control, we immunized rabbits of the same Ig phenotype but born to homozygous mothers, and therefore not exposed to that allotype. Immunization was done in a3/a3 offspring of either a1/a3 or a3/a3 mothers, by injecting a 1 IgG, and in b6/b6 offspring of b4/b6 or b6/b6 mothers, by injecting b4 IgG. The IgG was injected either in a soluble form or emulsified in adjuvant. Injection of soluble IgG elicited only a low response, if any, revealing no differences between the various groups. All rabbits responded upon immunization with IgG in adjuvant. We have not found any good evidence for natural tolerance to a non-inherited allotype, although progeny of a1/a3 mothers had slightly decreased responses to a1. On the contrary, progeny of b4/b6 mothers responded even better than offspring of b6/b6 mothers, upon such immunization with b4. To induce tolerance experimentally, we injected newborn rabbits, either from heterozygous a1/a3 or from homozygous a3/a3 mothers, with a1 serum or IgG. Newborn of heterozygous b4/b6 or of homozygous b6/b6 mothers were injected with b4 serum or IgG in the same way. Such treatment resulted in partial tolerance to each allotype. In an attempt to amplify the tolerizing effect of the maternal a1 Ig, we injected newborn rabbits of a1/a3 mothers with the serum of their mother. The response upon subsequent immunization with a1 allotype of another individual did not differ significantly from the response of control rabbits. The response was much poorer when rabbits were injected with nonmaternal tolerogen at birth, and when the same Ig preparation was used as immunogen. In a control experiment, neonatal injection of xenogeneic proteins, human IgG or bovine serum albumin, clearly resulted in tolerance. We speculate that tolerance to allotypes is established in the T cell repertoire only but bypassed by recognition of idiotypic determinants on antigen molecules by helper T cells, which trigger anti allotype antibody formation by allotype-specific B cells. The end result of it is a lack of natural tolerance. PMID- 1915557 TI - Phagocytosis enhances murine macrophage activation by interferon-gamma and tumor necrosis factor-alpha. AB - Previously, we reported that exposure of bone marrow-derived macrophages (M phi) to a phagocytic stimulus in the simultaneous presence of interferon-gamma (IFN gamma) induced these cells to generate nitrite (NO2-). This effect was achieved using both living (i.e. promastigotes of the protozoan parasite Leishmania enriettii) and inert (latex beads) particles. When the phagocytic stimulus was Leishmania, enhanced intracellular killing accompanied elevated NO2- secretion. As shown here, the capacity of phagocytosis to elicit NO2- production by IFN gamma-treated M phi was inhibited by antibody to murine recombinant tumor necrosis factor-alpha (rTNF-alpha), suggesting that phagocytosis enabled IFN gamma to activate M phi via the induction of TNF-alpha as an autocrine second signal. M phi NO2- production in response to rIFN-gamma and either exogenous TNF alpha or Leishmania was strongly enhanced by prostaglandin E2, consistent with such a mechanism. However, addition of either Leishmania promastigotes or latex beads to M phi cultures simultaneously exposed to both IFN-gamma and exogenous murine or human rTNF-alpha further potentiated activation as measured by NO2- release. Furthermore, anti-TNF antibody failed to inhibit M phi responses to rIFN gamma and bacterial lipopolysaccharide (LPS) in the presence or absence of Leishmania; also exogenous rTNF-alpha did not significantly affect NO2- production by IFN-gamma/LPS cultures despite a strong enhancement by Leishmania. These results suggest that phagocytosis enhances M phi responses by a process more complex than the sole induction of TNF-alpha. Phagocytosis also increased M phi NO2- production elicited by IFN-gamma plus TNF-alpha in L-arginine-deficient media. These results indicate that phagocytosis may be an important mechanism of up-regulating M phi microbicidal activity, and could be particularly relevant upon arginine depletion which occurs during an inflammatory response. PMID- 1915558 TI - Interferon-gamma inhibits serotonin release from mouse peritoneal mast cells. AB - Conditioned medium (CM) from concanavalin A-activated mouse spleen cells inhibits antigen-induced 5-hydroxytryptamine (5-HT) release from mouse peritoneal mast cells when added for 24 or 48 h to cell cultures containing monoclonal IgE sensitizing antibody. We present the following evidence that the spleen cell derived inhibitory factor is interferon-gamma (IFN-gamma): (a) CM from Con A activated spleen cells and from Chinese hamster ovary (CHO) cells transfected with the murine (Mu)IFN-gamma gene both produced a graded inhibition of 5-HT release when added to peritoneal cell cultures containing IgE and subsequently challenged with antigen; (b) the relative inhibitory potency of the two preparations corresponded to their relative IFN content as determined by antiviral bioassay; (c) the inhibitory activity of spleen cell CM and of CM from IFN-gamma gene-transfected CHO cells was abolished by treatment with a rat monoclonal MuIFN-gamma-neutralizing antibody, i.e. 5-HT release returned to control levels, and (d) a highly immunopurified preparation of recombinant MuIFN gamma retained the inhibitory activity, and was active at concentrations as low as 2 U/ml. The inhibitory activity of IFN-gamma appeared to be a direct effect of the cytokine on mast cells, since CM generated for different time periods from unfractionated peritoneal cells treated with purified recombinant MuIFN-gamma contained no inhibitory activity other than IFN-gamma itself, as demonstrated by neutralization of the cytokine with monoclonal antibody. Furthermore, purified recombinant MuIFN-gamma was equally active on mast cells enriched by density centrifugation up to 95% purity as on unfractionated peritoneal cells (1%-2% mast cells). Purified recombinant MuIFN-gamma inhibited 5-HT release induced by a range of different cell activators, namely antigen, anti-IgE, compound 48/80 and calcium ionophore A23187. Hence inhibition is not specific to IgE-dependent activation of mast cells, but seems to be directed more generally at the secretory process of these cells. PMID- 1915559 TI - Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF), in addition to being a growth factor for granulocytes and macrophages, is an activator of cells of the monocyte/macrophage lineage and induces HLA class II expression and cytokine synthesis in these target cells. Macrophage activation and class II expression are prominent features in rheumatoid arthritis (RA) joints, but the mechanism of their stimulation is not understood, since interferon-gamma, the major stimulus of class II expression, is not usually detectable at the protein level in synovial cell culture supernatants. We have, therefore, studied GM-CSF expression in cultures of cells derived from joints affected by RA and osteoarthritis (OA), and show that GM-CSF is produced spontaneously both by RA synovial cells and to a lesser extent by OA synovial cells in the absence of extrinsic stimuli. GM-CSF production continues for the 5-day duration of the culture period. Using neutralizing antibodies to tumor necrosis factor (TNF)-alpha we demonstrated that GM-CSF production in RA synovial cell cultures is dependent on the continued presence of active TNF-alpha. This result supports our concept that continued activation of the cytokine network is a marked feature of RA, and that TNF-alpha plays a pivotal role in this network, by regulating the production of other pro inflammatory cytokines, such as interleukin 1, as demonstrated previously, and GM CSF. PMID- 1915560 TI - Expression and regulation of beta 7(beta p) integrins on mouse lymphocytes: relevance to the mucosal immune system. AB - A mouse lymphocyte surface molecule which is selectively expressed by mucosal T cells and detected with the monoclonal antibody (mAb) M290 has provisionally been identified as a beta 7 integrin. Identification was based on close homology of its beta subunit at the N terminus with the recently reported, highly distinctive, human beta 7 sequence. mAb were prepared against the beta and alpha subunits of the mouse molecule, termed beta 7 and alpha M290, respectively, and used to study surface expression of the two components. beta 7 was present on most lymph node lymphocytes in association with alpha 4 rather than alpha M290. This integrin, beta 7 alpha 4, was shown to be identical to LPAM-1 (beta p alpha 4) the Peyer's patch homing receptor. Stimulation in vitro of mouse lymph node T cells with anti-CD3 in the presence of transforming growth factor (TGF)-beta increased beta 7 expression in about 40% of cells and changed the associated alpha chain from alpha 4 to the novel alpha M290 subunit, which, in most cells, was expressed de novo. Immunoprecipitation of beta 7 both from these cells and from intraepithelial lymphocytes gave closely similar results and showed predominance of the beta 7 alpha M290 integrin. It is suggested that in vivo this change in alpha-chain usage occurs in mucosal T cells in response to TGF-beta acting in the mucosal microenvironment and that the new integrin confers particular adhesive properties, possibly homing specificity, on the cells. PMID- 1915561 TI - Rat "first-wave" mature thymocytes: cycling lymphoblasts that are sensitive to activation-induced cell death but rescued by interleukin 2. AB - The sequential appearance of thymocyte subsets in rat ontogeny was studied using the surface markers CD4, CD8, and the alpha/beta T cell receptor (here referred to as TcR). It was noted that the first TcRhigh thymocytes, appearing around birth, are not resting lymphocytes but cycling blast cells. These "first wave" TcRhigh cells are medullary in location and predominantly of the CD4/CD8 "single positive" phenotype. Only about 5% express the light chain of the interleukin (IL)2 receptor, indicating that binding of IL 2 to high-affinity receptors is not driving proliferation of these blasts. Newborn TcR high blast cells were purified and analyzed in vitro. When cultured without further additions, they rapidly stopped cycling. Stimulation with cross-linked anti-TcR monoclonal antibody plus IL 2 resulted in vigorous and rapid proliferation that exhibited accelerated kinetics as compared to peripheral resting T cells. In contrast, TcR cross linking without exogenous IL 2 induced cell death. This TcR-induced cell death involved fragmentation of DNA characteristic of apoptosis that was readily detectable within 18 h of culture. Addition of IL 2 to these short-term cultures prevented TcR-induced DNA fragmentation. Together, these results suggest that in newly formed TcRhigh thymocytes, TcR engagement results in clonal deletion if the IL 2 receptor remains unoccupied but allows clonal expansion if IL 2 is provided. This mechanism may be operative in the establishment of self-tolerance during T cell development. PMID- 1915562 TI - Cyclosporin A blocks surface IgM-mediated growth inhibition in an immature B lymphoma, BKS-2. AB - Cyclosporin A (CSA) is an immunosuppressive drug, which blocks selective activation pathways in T and B cells. Antigen receptor-mediated signaling events have been shown to be very sensitive to CSA. Signaling through the surface IgM receptor had been shown to induce growth inhibition in immature B cell lymphoma cells. In this report, we demonstrate that CSA caused significant reversal of growth inhibition induced by an anti-mu antibody in an immature B lymphoma, BKS 2. Time-course experiments indicated that CSA was completely effective when added as late as 4 h after the addition of ligand. CSA was also found to have no direct effect on anti-mu-induced Ca2+ elevation. These results suggest that the likely target for CSA lies downstream from the initial generation of second messengers, such as Ca2+. PMID- 1915563 TI - Glucocorticoids suppress the production of interleukin 4 by human lymphocytes. AB - Given that glucocorticoids (GCS) were reported to increase the production of interleukin 4 (IL4) by mouse T cells and that GCS are widely used to treat allergic diseases it was important to examine the effect of these agents on IL4 production by human lymphocytes. We here demonstrate that the production of IL4 by human lymphocytes is markedly inhibited by small concentrations of hydrocortisone. The suppression is observed at the protein and at the mRNA levels and it is not secondary to the GCS-induced inhibition of IL2 production. PMID- 1915564 TI - Effects of thyrotropin-releasing hormone on behavioral disturbances in middle cerebral artery-occluded rats. AB - The effects of thyrotropin releasing hormone (TRH) on behavioral and histological changes were studied in rats subjected to left middle cerebral artery occlusion. The drug was given i.p. once or several times a day from 1 week after occlusion for 2 weeks. A single administration of TRH (1 and 10 mg/kg) did not affect the neurological deficits, but recovery of the deficits was accelerated by multiple administration (7 times a day) of TRH and single administration (once a day) of YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), a new TRH analogue with a longer half-life. Both YM-14673 and single (1 and 10 mg/kg) and multiple administration of TRH ameliorated the disturbance of passive avoidance learning. Neuronal degeneration in the cerebral cortex and striatum was not influenced by the administration of TRH. Thus, we found that neurological deficits and disturbance of passive avoidance learning behavior in middle cerebral artery-occluded rats could be ameliorated by administration of TRH. PMID- 1915565 TI - Pituitary adenylate cyclase-activating polypeptide: a novel, long-lasting, endothelium-independent vasorelaxant. AB - The vasoactivity of the 27- and 38-amino acid forms of the novel peptide pituitary adenylate cyclase-activating polypeptide (PACAP) was tested in vitro. Both forms of PACAP caused endothelium-independent vasodilation (assayed by their vasodilator action on rabbit aorta). When superfused for 1 min the relaxation EC50 of PACAP27 was 23 +/- 8 nM and of PACAP38 was 152 +/- 66 nM. PACAP was 100 fold more potent than vasoactive intestinal polypeptide (VIP) (PACAP27 shows 68% amino acid sequence homology with VIP), and had a prolonged duration of action, a 1 min exposure to 1 microM PACAP27 lasting 135 +/- 7 min and to 1 microM PACAP38 108 +/- 3 min. Adenylate cyclase activity in homogenates of rabbit aortic smooth muscle cells was increased by PACAP27 and PACAP38 with EC50s of 4.4 and 0.73 nM, respectively. PACAP27 and PACAP38 are potent, long-lasting, endothelium independent vasodilators. PMID- 1915566 TI - Reserpine-induced reduction of in vivo binding of SCH 23390 and N-methylspiperone and its reversal by d-amphetamine. AB - In order to clarify the role of endogenous dopamine in the binding of [3H]SCH23390 and [3H]N-methylspiperone to the mouse striatum in vivo, the effects of reserpine and the reversal of these effects by d-amphetamine were investigated. Radioactivity was measured in the striatum and cerebellum following i.v. injection of each ligand into control and drug-treated mice. The ratio of radioactivity in the striatum to that in the cerebellum, plotted as a function of time, showed a linear correlation. Pretreatment with reserpine 24 h prior to injection of tracer significantly decreased the in vivo binding of both [3H]SCH23390 and [3H]N-methyl-spiperone in a dose-dependent manner. Saturation experiments indicated that these changes in in vivo binding were due mainly to changes in apparent affinity rather than to the number of binding sites available. Administration of d-amphetamine to reserpine-treated mice reversed the effect of reserpine in a dose-dependent manner. Blockade of dopamine D1 receptors with SCH23390 did not prevent the reversal by d-amphetamine of [3H]N methylspiperone binding in vivo; however, treatment with haloperidol did prevent the effect of d-amphetamine on [3H]SCH23390 binding. These results suggest that dopamine D2 receptor-mediated neurotransmission might itself regulate the binding of dopamine to receptors in vivo. PMID- 1915567 TI - Effect of cyclosporine on ornithine decarboxylase activity in rat submaxillary lymph nodes: modulation by sympathetic nerves. AB - In order to examine whether cyclosporine activity in submaxillary lymph nodes is dependent on sympathetic modulation, rats received a unilateral superior cervical ganglionectomy together with a contralateral sham-operation. Two weeks later, cyclosporine (5 or 20 mg/kg per day s.c.) was injected for five days. Freund's complete adjuvant was injected 1 h before the third injection of cyclosporine and the rats were killed 2 h after the last injection of cyclosporine. A significant increase in ornithine decarboxylase activity in submaxillary lymph nodes was observed two weeks after sympathetic denervation. Cyclosporine decreased enzyme activity in submaxillary lymph nodes on the sham-operated side by 67-77% and by 21-41% on the denervated side (P less than 0.01). The incorporation of [35S]methionine into proteins in ipsilateral submaxillary lymph nodes was increased by unilateral superior cervical ganglionectomy and decreased by cyclosporine to a similar extent in denervated and innervated lymph nodes. Superior cervical ganglionectomy decreased by about 93-95% the norepinephrine content of submaxillary lymph nodes regardless of cyclosporine treatment. The results indicate that an appropriate sympathetic neural environment is needed for cyclosporine to have an effect on ornithine decarboxylase activity in lymphoid tissue. PMID- 1915568 TI - Inhibitory effect of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) in vascular smooth muscle. AB - The inhibitory effects of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB 8) on vascular smooth muscle contraction and cytosolic Ca2+ level ([Ca2+]i) were examined using isolated rabbit aorta loaded with a fluorescent Ca2+ indicator, fura-2. TMB-8 (100 microM) decreased the high K(+)-induced increase in muscle tension, and [Ca2+]i and 45Ca2+ influx to their respective resting levels. TMB-8 (100 microM) almost completely inhibited the increase in [Ca2+]i and 45Ca2+ influx due to norepinephrine although muscle tension was only partially decreased. A higher concentration of TMB-8 (300 microM) inhibited the remaining portion of the contraction without additional decrease in [Ca2+]i. The inhibitory effect of TMB-8 on high K(+)-induced contraction, but not on the norepinephrine induced contraction, was antagonized by the increase in external Ca2+ concentrations or by the Ca2+ channel activators, CGP 28,392 and by Bay K8644. In Ca(2+)-free solution, norepinephrine-induced transient increases in [Ca2+]i and muscle tension and 100 microM TMB-8 inhibited these changes. The caffeine-induced transient increases in [Ca2+]i and muscle tension were also inhibited by TMB-8 at concentrations higher than those needed to inhibit the norepinephrine-induced transient changes. In permeabilized smooth muscle, TMB-8 (300 microM) did not inhibit the Ca(2+)-induced contraction. These results suggest that TMB-8 inhibits vascular smooth muscle contractility by inhibiting Ca2+ influx, Ca2+ release and Ca2+ sensitization of contractile elements. PMID- 1915569 TI - Administration of carbamazepine in the nucleus of the solitary tract inhibits the antihypertensive effect of clonidine. AB - The effects of carbamazepine administration into the nucleus tractus solitarii (NTS) on central alpha 2-adrenergic cardiovascular function were studied in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Stereotaxic microinjections of carbamazepine (288 ng/60 nl) into the NTS of SHR transiently increased blood pressure, heart rate, and renal sympathetic nerve activity. These effects were followed by a modest depressor and bradycardic effect, with no change in sympathetic nerve activity. In addition, previous intra NTS administration of carbamazepine attenuated the antihypertensive effect of the centrally acting alpha 2-adrenoceptor agonist, clonidine. Similar carbamazepine effects were observed in the WKY rats. These results suggest that some of the cardiovascular changes observed during carbamazepine treatment involve antagonism of central noradrenergic mechanisms. PMID- 1915570 TI - Blockade of morphine place conditioning by the CCKA receptor antagonist devazepide. PMID- 1915571 TI - 13-hydroxy-linoleic acid induces airway hyperreactivity to histamine in guinea pigs. PMID- 1915572 TI - Cocaethylene inhibits dopamine uptake and produces cocaine-like actions in drug discrimination studies. PMID- 1915573 TI - L-NG-nitro arginine produces an exaggerated hypertension in anesthetized SHR. PMID- 1915574 TI - Role of sulfhydryl groups in the stimulatory effect of captopril on vascular prostacyclin synthesis. AB - The effect of captopril on vascular prostacyclin production was studied, evaluating which of its components--sulfhydryl (SH) group or proline--is responsible for this effect. Rat aortas were incubated with captopril (10-100 microM), 2-mercaptoethanol or proline (10 microM), and captopril plus the SH binding reagents N-ethylmaleimide or ethacrynic acid (50 microM). Prostacyclin was measured by radioimmunoassay of 6-keto-prostaglandin F1 alpha. Captopril stimulated prostacyclin production. This effect was associated with an enhanced conversion of arachidonate to prostacyclin and was not related to bradykinin. Since 2-mercaptoethanol increased vascular prostacyclin per se and proline did not, the stimulatory effect of captopril appears to be dependent upon the SH group; in addition, both SH blockers, N-ethylmaleimide and ethacrynic acid, antagonized this effect. This study shows that captopril stimulates vascular prostacyclin synthesis directly and that the SH group plays a key role in this action. This stimulation of prostacyclin synthesis may contribute to the antihypertensive action of captopril. PMID- 1915575 TI - Antagonism by propyl-beta-carboline-3-carboxylate of passive avoidance impairment induced by diazepam. AB - We investigated the effects of propyl-beta-carboline-3-carboxylate (beta-CCP) on learning and memory tasks in a passive avoidance test in mice to clarify whether beta-CCP is an agonist or antagonist at benzodiazepine (BZP) receptors. At doses up to 10 mg/kg i.v., beta-CCP had no effect on mice in the passive avoidance test. Diazepam impaired passive avoidance behavior and methyl-beta-carboline-3 carboxylate(beta-CCM) enhanced it. beta-CCP blocked these effects of diazepam and beta-CCM in a dose-dependent manner similar to the effect of Ro15-1788. These effects of beta-CCP, which are thought to be mediated by BZP receptors, indicate that beta-CCP is an antagonist in the passive avoidance test. PMID- 1915576 TI - A role for nitric oxide in capsaicin-induced gastroprotection. PMID- 1915577 TI - Contractile effects and binding properties of endothelins/sarafotoxins in the guinea pig ileum. AB - Seven of the eight known isopeptides of the endothelin/sarafotoxin (ET/SRTX) family were tested on the isolated guinea pig ileum and found to cause a concentration-dependent increase in basal tone. The rate or the amplitude of the spontaneous rhythmic contractions of the ileal smooth muscle were essentially not affected by any of the peptides. The maximum contraction elicited by vasoactive intestinal contractor (VIC) was slightly stronger than that induced by endothelin 1 (ET-1) or sarafotoxin-b (SRTX-b), and significantly stronger than the maximal contractions elicited by sarafotoxin-a (SRTX-a), sarafotoxin-c (SRTX-c), or endothelin-3 (ET-3). Sarafotoxin-d (SRTX-d) caused, essentially, no contraction but a rather marked relaxation. The potencies of the various peptides to induce the increase in tension, in terms of EC50 values (cumulative effective concentrations that induce half-maximum response), ranged between 6 and 95 nM depending on the peptide. VIC, ET-1, SRTX-b and SRTX-a had similar potencies and were significantly more potent than SRTX-c and ET-3. A high concentration of SRTX b elicited no additional response when applied to the organ bath after one of the other peptides had shown a maximal effect. Binding experiments with ileal membranes revealed similar binding properties for the various peptides. Competition with iodinated SRTX-b showed no meaningful differences between the various peptides. It is concluded that all the ET/SRTX peptides compete for the same receptor subtype in the ileum. In terms of efficacy, VIC can be considered as a full agonist of this receptor, SRTX-d is probably an antagonist, while all the other peptides behave as partial agonists. PMID- 1915578 TI - The effects of tianeptine on wet-dog shakes, fore-paw treading and a flexor reflex in rats are consistent with enhancement of 5-hydroxytryptamine uptake. AB - Tianeptine is a novel antidepressant which uniquely facilitates 5 hydroxytryptamine (5-HT) uptake. When given in a dose of 10 mg/kg to rats pretreated with either carbidopa or phenelzine, it markedly reduced the frequency of wet-dog shakes, fore-paw treading, tremor and hind-limb abduction evoked by L 5-hydroxytryptophan (L-5-HTP) given 30 or 60 min later. This effect of tianeptine was opposite to that of paroxetine, a selective 5-HT uptake inhibitor, which greatly increased the 5-HTP-induced behavioural syndrome. In contrast, tianeptine did not affect behaviours elicited by the 5-HT receptor agonists, 5-methoxy-N,N dimethyltryptamine (5-MeODMT) or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane hydrochloride (DOI), which are not substrates for the 5-HT uptake process. In spinal animals, tianeptine attenuated an ipsilateral flexor reflex, an effect opposite to that of citalopram, a selective 5-HT uptake inhibitor. These effects of tianeptine are consistent with its ability to increase 5-HT reuptake. PMID- 1915579 TI - Studies of the renin-angiotensin system in the wall of rat femoral resistance vessels. AB - The responses to angiotensinogen, angiotensinogen-(1-14) (tetradecapeptide, TDP), angiotensin I, and angiotensin II and the effect of the renin inhibitor, CH-66, the angiotensin-converting enzyme (ACE) inhibitor, perindopril, and the receptor antagonist, saralasin, were investigated in isolated femoral resistance arteries of the rat. The response to angiotensinogen in the presence of kallikrein was also investigated. Angiotensin I and TDP elicited a contraction which was not reduced by CH-66 but was inhibited by perindopril and saralasin. The response to angiotensinogen was small and not blocked by saralasin but the response to angiotensinogen that was mixed with renin for a few seconds was saralasin sensitive and perindopril and CH-66 showed a tendency to block this response. The response to angiotensinogen was enhanced in the presence of kallikrein. These results suggest (1) the presence of a partial renin-angiotensin system (RAS) in this preparation, (2) that TDP is not converted via renin while both angiotensin I and TDP are converted through ACE in this preparation and (3) that the responses to angiotensinogen and TDP are different. PMID- 1915580 TI - Effect of NZ-107 on late-phase airway responses and airway hyperreactivity in guinea pigs. AB - The effect of NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H) pyridazinone) on late-phase airway responses and airway hyperreactivity was investigated in the guinea pig. Challenge with inhaled ovalbumin in conscious guinea pigs actively sensitized with inhaled ovalbumin caused triphasic bronchial obstruction, which peaked at 5-30 min, 6-8 h and 24 h. In this model, airway hyperreactivity to acetylcholine was observed 48 h after antigen challenge. Orally administered NZ-107, given 2 h before ovalbumin challenge significantly inhibited airway responses at 5-30 min (10 mg/kg), 6-8 h (30 mg/kg), 24 h (10 mg/kg) and airway hyperreactivity (30 mg/kg). When NZ-107 (10 mg/kg) was orally administered to the guinea pigs 3 h after ovalbumin challenge, it also inhibited airway responses at 6-8 h and 24 h and airway hyperreactivity. In anaesthetized guinea pigs, intravenous administration of NZ-107 (0.03-1.0 mg/kg) inhibited platelet-activating factor (PAF)- and propranolol-induced airway hyperreactivity to histamine. These results suggest that NZ-107 may be a useful drug for the treatment of bronchial asthma by reducing late-phase airway responses and airway hyperreactivity. PMID- 1915581 TI - Dual regulation of pancreatic vascular tone by P2X and P2Y purinoceptor subtypes. AB - The effects of ATP on the pancreatic vascular bed of the rat were studied under resting tone. ATP exerted two different effects depending on the concentration used: a slight vasodilatation in the 1.65-49.5 microM range which was statistically significant only at 16.5 microM and a concentration-related vasoconstriction in the 495-4 950 microM range. Theophylline, a P1 purinoceptor antagonist, did not modify the vasodilator effect of ATP. The existence of two P2 purinoceptor subtypes (P2y and P2x) in our preparation may be responsible for the dual effect of ATP. The P2y antagonist 2,2'pyridylisatogen (PIT) used at 5 microM, revealed a vasoconstrictor effect of ATP 165 microM, a concentration without effect per se. Furthermore, the transient vasoconstrictor effect of ATP 495 microM was changed into a long-lasting one in the presence of PIT. On the other hand, the blockade of P2x purinoceptors by the desensitizing agent, alpha,beta-methylene ATP, increased the vasodilator effect of ATP 16.5 microM. In conclusion, two subtypes of P2 purinoceptor do exist on the pancreatic vascular bed: P2y inducing vasodilatation and P2x inducing vasoconstriction. At vascular resting tone, the effect observed with ATP therefore depends on the concentration used and on the balance between P2y/P2x purinoceptors. PMID- 1915582 TI - Inhibition of 5-hydroxytryptamine neuronal activity by the 5-HT agonist, DOI. AB - Systemic, intra-raphe and microiontophoretic administration of the 5 hydroxytryptamine (5-HT)1C/5-HT2 agonist (1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane (DOI) inhibited the firing of 5-HT neurones in the dorsal raphe. DOI administered systemically and directly into the raphe also decreased the extracellular concentration of 5-hydroxytryptamine (5-HT) in the frontal cortex. In contrast, the administration of DOI directly into the frontal cortex did not significantly alter the concentration of frontal cortical extracellular 5-HT. The reduction of the firing rate of 5-HT neurons in the dorsal raphe and extracellular 5-HT concentration in the frontal cortex induced by systemic administration of DOI could not be blocked by the 5-HT2 antagonist ketanserin, ritanserin (5-HT2/5-HT1C antagonist) or the putative 5-HT1A antagonist, pindolol. These results suggest that the inhibition of 5-HT neuronal firing seen with administration of DOI is mediated via an action within the dorsal raphe and at least in close proximity to the 5-HT neurone cell bodies. The decrease in frontal cortical extracellular concentration of 5-HT release was not due to a direct action in the frontal cortex itself and may possibly be as a result of the decrease in the firing rate of the 5-HT neurones in the dorsal raphe. The mechanism of action of DOI to produce these effects is, however, unclear and warrants further investigation. PMID- 1915583 TI - Anticonvulsant and sleep-waking influences of riluzole in a rat model of absence epilepsy. AB - Six WAG/Rij rats, an animal model of human absence epilepsy, were injected intraperitoneally with riluzole. At 4 mg/kg, riluzole decreased the number, mean duration and spike-frequency of the spontaneously occurring discharges for 3 h. Riluzole also increased slow wave sleep at the expense of waking. As riluzole at 3 mg/kg decreased the number and spike-frequency of the discharges without inducing a sedative effect, this compound could be of therapeutic interest in human absence epilepsy. PMID- 1915584 TI - Human alpha-calcitonin gene-related peptide (CGRP)-(8-37), but not -(28-37), inhibits carotid vasodilator effects of human alpha-CGRP in vivo. AB - Human alpha-calcitonin gene-related peptide-(8-37) alone (up to doses of 30 nmol kg-1 min-1) had no significant effects on blood pressure, heart rate or common or internal carotid haemodynamics, although it caused significant, reversible, inhibition of the hypotensive, tachycardic, and common and internal carotid vasodilator effects of human alpha-CGRP (0.03 nmol kg-1 min-1) in conscious, Long Evans rats. Human alpha-CGRP-(28-37) up to doses of 300 nmol kg-1 min-1 had no cardiovascular effects itself and did not influence responses to human alpha CGRP. These results are consistent with the carotid haemodynamic effects of human alpha-CGRP being due largely to activation of the CGRP1-receptor subtype. PMID- 1915585 TI - Possible involvement of nitric oxide in long-term potentiation. AB - Long-term potentiation (LTP) in the hippocampus is known to involve NMDA (N methyl-D-aspartate) receptors. Since activation of NMDA receptors in the cerebellum results in the formation of nitric oxide (NO), we studied the possible involvement of this messenger in hippocampal synaptic plasticity. We report here that the NO-synthase inhibitor, L-N omega-nitro-arginine, blocks LTP and that sodium nitroprusside, which releases NO, produces a long-lasting enhancement in synaptic efficacy which is not additive with tetanus-induced LTP. PMID- 1915586 TI - Effect of cicletanine on overpacing-induced ST-segment elevation in conscious rabbits. A comparison with verapamil. AB - We compared the effects of cicletanine (10 mg/kg i.v.) and verapamil (0.1 mg/kg i.v.) on heart rate, ventricular effective refractory period, systolic and diastolic arterial blood pressure and overpacing-induced ST-segment elevation detected by right ventricular intracavital electrogram in conscious rabbits. Cicletanine significantly reduced overpacing-induced ST-segment elevation, which is an indicator of myocardial ischemia, and heart rate, but did not influence blood pressure and ventricular effective refractory period. Verapamil did not significantly influence ventricular effective refractory period, blood pressure or heart rate, but reduced the ST-segment elevation induced by frequency loading. These results suggest that acute treatment with cicletanine induces an anti ischemic effect in the overpaced heart of conscious rabbits. PMID- 1915587 TI - NPC 15669 enhances survival and reverses leukopenia in endotoxin-treated mice. PMID- 1915588 TI - Calcium influx modulates DNA synthesis and proliferation in A7r5 vascular smooth muscle cells. AB - In A7r5 vascular smooth muscle cultures basal Ca2+ influx was higher in growing versus quiescent cells (P less than 0.05), due primarily to a five-fold increase in dihydropyridine-inhibitable Ca2+ influx (P less than 0.005). Verapamil decreased [3H]thymidine incorporation in a concentration dependent fashion with a significant 6 +/- 2% inhibition at 0.1 microM and a maximal inhibition of 67 +/- 2% at 100 microM. Similarly, nitrendipine inhibited fetal calf serum-stimulated [3H]thymidine incorporation with a threshold concentration of 1 nM and a maximal inhibition of 79 +/- 12% at 10 microM. In quiescent cells, verapamil (10 microM) inhibited the increases in [3H]thymidine incorporation stimulated by fetal calf serum, serotonin, vasopressin or 12-0-tetradecanoyl phorbol-13-acetate by 37-43% (P less than 0.001 vs. control for all). Finally, verapamil (100 microM) and nitrendipine (10 microM) inhibited proliferation by 39 +/- 10 and 20 +/- 6%, respectively (P less than 0.01 and 0.02 vs. control, respectively). Thus in A7r5 cells, proliferation is associated with increased Ca2+ influx via dihydropyridine sensitive Ca2+ channels and organic Ca2+ channel antagonists inhibit DNA synthesis and cell proliferation. PMID- 1915589 TI - Carbamazepine distinguishes between adenosine receptors that mediate different second messenger responses. AB - The mechanism of the therapeutic and prophylactic effects of carbamazepine (CBZ) in affective psychoses is unknown but may in part be related to the potent competitive interaction of CBZ with adenosine-binding sites in the brain. The anticonvulsant and sedative properties of CBZ are reminiscent of the effects evoked by adenosine-agonists and contrast sharply with the opposite actions of adenosine-antagonists like caffeine. However, indirect evidence suggests an antagonist- rather than an agonist-like activity of CBZ at adenosine-receptors. We have used various model systems, in which adenosine receptor subtypes mediate different second messenger-responses, to investigate this-apparent paradox. CBZ was found to antagonize the A1-receptor-mediated inhibition of cyclic AMP accumulation in cultured astroblasts and in GH3-cells. Furthermore, CBZ also inhibits the adenosine-induced increase in the level of cyclic AMP in cultured astroblasts, which is mediated by low-affinity A2b-receptors. In contrast, CBZ does not block the inhibition elicited by adenosine-agonists of the agonist induced increased formation of inositolphosphates in human neutrophils, which is mediated by high-affinity A2a-receptors. The specific antagonism by CBZ of A1- but not of high-affinity A2a-receptors was further supported by binding experiments using rat brain membranes. These results suggest that the paradox of CBZ's antagonistic effects at adenosine-receptors might be at least partially reconciled by a selective antagonistic action of CBZ at A1 receptors but not at high-affinity A2a-receptors. PMID- 1915590 TI - Action of organic solvents on protein kinase C. AB - The action of organic solvents on the biochemical and biophysical properties of protein kinase C (PKC) was measured in a defined lipid vesicle system. Chloroform, benzyl alcohol and ethanol all partially activated PKC. They had no effect on the Ca(2+)- or anionic phospholipid-, phosphatidylserine-dependence. Their ability to activate PKC correlated with their lipid perturbing effect as measured by the decrease in fluorescence anisotropy. Chloroform was the most potent activator stimulating PKC phosphotransferase activity up to a level 40% of that obtained by the endogenous activator, diacylglycerol. The three fluidizers induced a more hydrophobic environment for at least one PKC tryptophan residue. This may have been due to insertion of an additional or different region of protein kinase C into the lipid bilayer as demonstrated by a blue shift in tryptophan fluorescence, providing an explanation for their inability to act as competitors of PKC binding of phorbol esters. Higher concentrations of the organic solvents resulted in a lipid bilayer that was too fluid to support membrane activity. This study demonstrates that these anesthetics and alcohols modulate lipid structure which subsequently induces PKC to undergo a different protein-lipid interaction in comparison to the endogenous activator, diacylglycerol. This supports the proposal that the biophysical state of the membrane plays a significant role in modulating PKC activity. PMID- 1915591 TI - Mapping the xanthine C8-region of the adenosine A1 receptor with computer graphics. AB - Substitution at the 8-position of 1,3-dipropylxanthines can lead to very potent and selective adenosine A1 antagonists. The xanthine C8-region was investigated in this study, using CAMM (computer-assisted molecular modeling). This region can be divided into two subregions with a considerable overlap in volume: a phenyl region which binds the flat substituents and a cycloalkyl region which binds the other substituents. The 8-phenyl-substituted derivatives bind with an N9-C8-Cl' C2' dihedral angle of 220 degrees; this dihedral angle is 330 degrees for the 8 cycloalkyl-substituted derivatives. The lower affinity of C8-substituted 7-methyl 1,3-dipropylxanthines can be explained quantitatively with steric hindrance, which C8-substituents experience from the 7-methyl group in these conformations. The substitution pattern determines the affinity for 8-phenyl-substituted compounds for which the energy cost to reach the dihedral angle of 220 degrees is low, but has little influence otherwise. The affinity of the 8-cycloalkyl-1,3 dipropylxanthines is mainly volume dependent, because of a forbidden area near the cycloalkyl region. PMID- 1915592 TI - Polymyxin B is a selective and potent antagonist of calmodulin. AB - Polymyxin B, a cyclic peptide antibiotic, is considered to be a rather selective antagonist of protein kinase C. This drug is therefore widely used to evaluate the involvement of protein kinase C in cellular processes. In the present study, we investigated the effects of polymyxin B on the activity of calmodulin dependent cyclic 3':5'-nucleotide phosphodiesterase in vitro. The drug potently inhibited this enzyme (IC50 80 nM in the presence of 500 microM Ca2+), while about 200-fold higher concentrations were required to inhibit protein kinase C to the same extent. Phosphodiesterase inhibition was competitive with respect to Ca2+ and calmodulin. Evidence for the formation of a complex between polymyxin B and calmodulin was obtained by polyacrylamide gel electrophoresis under non denaturing conditions, and by affinity chromatography of calmodulin on polymyxin B-agarose. We therefore suggest that, at least in vitro, polymyxin B is a potent and selective inhibitor of calmodulin. PMID- 1915594 TI - Inhibition of gamma-aminobutyrate and glycine uptake into synaptic vesicles. AB - The substrate specificity of vesicular GABA and glycine uptake was studied in vesicle fractions from brain and spinal cord, respectively. Glycine, beta-alanine and gamma-vinyl-GABA were competitive inhibitors of the GABA uptake were competitive inhibitors of the GABA uptake by synaptic vesicles in brain. Likewise GABA and beta-alanine turned out to be competitive inhibitors of vesicular uptake of glycine in spinal cord. The apparent K1 values were in the same range as the respective Km values for the transport systems. Accumulation of different amino acids were examined, and the structurally related amino acids GABA, beta-alanine and glycine were all taken up by both vesicle fractions. In the present study, we suggest that there are similarities in the vesicular transporters for GABA and glycine, and the two amino acids are probably taken up into the same vesicle population. The key factor in differentiating between GABA and glycine as transmitters in the terminals could be the synthesis and the high-affinity synaptosomal uptake. PMID- 1915593 TI - Modulation of [3H]glibenclamide binding to cardiac and insulinoma membranes. AB - The existence of a single or of multiple populations of glibenclamide binding sites is a subject of controversy. In the present study, radioligand binding techniques were employed to determine whether multiple populations of [3H]glibenclamide binding sites exist in pancreatic tumor (insulinoma) cells. Additional studies were performed to further characterize the binding of [3H]glibenclamide to insulinoma and cardiac membranes. [3H]Glibenclamide bound to high (0.1 nM) and low (240 nM) affinity binding sites in insulinoma membranes. The physiological relevance of multiple populations of sites is unknown. The binding of glibenclamide to insulinoma and cardiac membranes was altered by guanine nucleotides and not adenine nucleotides. This suggests glibenclamide binding can be modulated by G-proteins. Glibenclamide binding was also modulated by divalent cations. The divalent cations, Ca2+ and Zn2+, stimulated specific glibenclamide binding to cardiac and insulinoma membranes, while Mg2+ and Mn2+ enhanced cardiac binding only. Moreover, the lowering of pH from 7.4 to 6.5 was found to enhance specific glibenclamide binding. Interestingly, the magnitude of this effect was much larger in cardiac membranes. The specific nature of the regulation of glibenclamide binding by guanine nucleotides, divalent cations and pH remains to be explored. PMID- 1915596 TI - Early bone lesions in the hyperparathyroidism of hyperlipidemic rats. AB - Hyperlipidemic rats were examined histopathologically at 10, 14, 18 and 22 weeks of age for evaluation of early bone lesions in renal secondary hyperparathyroidism. Serum chemistry revealed that the mean levels of total cholesterol, triglyceride and phospholipid were greater than the respective control levels at 10 weeks of age, and that they increased with age. The mean levels of urea nitrogen, creatinine, inorganic phosphorus and calcium were also greater than the respective control levels at and after 14 weeks of age. Grossly, the kidney showed enlargement with an irregular surface and the parathyroid gland was swollen at and after 14 weeks of age. Histologically, the bone showed proliferation and hypertrophy of osteoblasts, an increase in osteoid seams, and an increase in and irregularity of the cement lines. These changes were first seen at 14 weeks of age, and became more severe with age. In addition, osteoclasts were increased at and after 18 weeks of age, and the parathyroid gland was enlarged at and after 14 weeks of age. On the other hand, segmental glomerular sclerosis was detected at 10 weeks of age, and became more severe with increasing age. PMID- 1915595 TI - Benextramine irreversibly inhibits [125I]neuropeptide Y affinity labeling of the Y2 binding protein in bovine hippocampus. AB - Affinity labeling of iodinated neuropeptide Y (NPY) to bovine hippocampal binding proteins revealed that benextramine inhibited specific NPY labeling of the 50 kDa NPY binding protein (Y2 binding protein) in a dose-dependent manner (IC50 = 33 microM). Hippocampal membranes, which were pretreated with benextramine and washed, exhibited decreased [125I]NPY labeling of binding proteins in a similar dose-dependent manner. These findings demonstrate that benextramine irreversibly blocks specific NPY binding to the 50 kDa NPY Y2 binding protein. PMID- 1915597 TI - Effect of the energy density of non-purified diets on growth, gestation and lactation in mice. AB - The effects of dietary energy density on the performance of growing, gestating and lactating C57BL/6J mice were determined in order to develop pelleted non purified practical diets for use in all stages of the mouse life cycle. Experimental diets with 4 levels of energy at 24% crude protein (CP) were pelleted and the nutritional values were determined using adult rats. The nitrogen-corrected metabolizable energy (MEn) values ranged from 2.86 to 3.73 kcal/g and the digestive CP (DCP) contents ranged from 20.5 to 22.6% on a dry matter (DM) basis. Mice responded to decreased dietary energy by increasing their feed intake to maintain MEn intake levels, except for 1 week after weaning and during lactation periods. During these periods, mice fed lower energy diets could not consume as much MEn as those fed higher energy diets. The lowest energy diet, in comparison with the highest energy diet, resulted in approximately a 33% lower weaning weight of pups at 3 weeks of age, a 13.2 to 34.4% slower growth at 3 to 4 weeks of age, and a 9.3 day delay in the onset of vaginal opening in young females. Lower energy diets, however, did not affect the litter size or the birth weight of pups. The DCP intake usually increased with decreases in dietary energy but apparently this did not affect the performance of the mice. It was concluded that an optimal diet should have an MEn value of 3.73 kcal/g DM or more for both the one week post weaning growth period and during lactation, but a diet with an MEn value of 2.86 kcal/g DM was sufficient for growth after 4 weeks of age and during gestation. PMID- 1915599 TI - [Diabetic peculiarity of the ALS-Ay and ALR-Ay strains]. AB - ALS and ALR mice were developed as mouse models of alloxan-induced diabetes. These strains do not show spontaneous onset of diabetes. When an obesity gene (Ay) was introduced to these two strains, severe diabetic conditions occurred spontaneously in the produced ALS-Ay and ALR-Ay strains. These strains were examined body weight gain, food consumption, water consumption, urinary sugar content, ketone body level and blood sugar level, and subjected to glucose tolerance test. As a result, in comparison with ALS mice, male ALS-Ay mice showed no obesity and very low tolerance to the glucose tolerance test performed 24 weeks after birth. The level of insulin secretion was 5.0 microU/ml or less, showing hardly any secretory reaction. On the other hand, female ALS-Ay mice were obese and showed no marked decrease in glucose tolerance. The level of insulin secretion was high, and the secretory reaction was strong. In ALR-Ay strain, both male and female mice were obese and showed diabetic conditions similar to those of ALS-Ay mice, though the severity tended to be lower. The characteristic features of diabetic conditions in these mice suggest that these strains, particularly ALS-Ay, may serve as useful new-type models of diabetes. PMID- 1915598 TI - [Canonical discriminant analysis for hematological and serum biochemical changes during pregnancy period in squirrel monkeys (Saimiri sciurea)]. AB - Hematological and serum biochemical data obtained from non-pregnant, pregnant and post-partum squirrel monkeys (Saimiri sciurea) were analyzed by canonical discriminant analysis (discriminant analysis with reduction of dimensionality). All animals were of wild origin and had been maintained under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N.I.H., Japan. Months were standardized by the day of parturition. The calculated arithmetic means and standard deviations were listed for each item of measurement performed. Items detected statistically significant difference (p less than 0.01) between months were as follows: red blood cell count (RBC), mean corpuscular volume (MCV), hematocrit value (Ht), hemoglobin concentration (Hb), white blood cell count (WBC), albumin concentration (ALB), blood urea nitrogen concentration (BUN), total cholesterol concentration (T-CHO), triglyceride concentration (TG), alkaline phosphatase activity (ALP) and calcium concentration (Ca). Results of canonical discriminant analysis showed that the value of the first canonical variate (Z1) decreased from the early period of pregnancy to the middle period, and that the second canonical variate (Z2) decreased from the middle period of pregnancy to the end of pregnancy. The meaning of their changes were discussed. PMID- 1915600 TI - Evaluation of a new tail-cuff method for blood pressure measurements in rats with special reference to the effects of ambient temperature. AB - We evaluated a recently developed tail-cuff apparatus for the indirect blood pressure measurement in rats with special reference to the effects of ambient temperature. For this purpose, we designed two preparations 1) an intact preparation to determine the effect of ambient temperature on blood pressure measurements and 2) an anesthetized and catheterized preparation for comparison of the values of blood pressure obtained by the indirect and by the direct method. This apparatus also required enough pulse volume oscillations to measure the accurate value of blood pressure. Sufficient pulse volume oscillations were obtained within 20 min at 30 and 40 degrees C. At 40 degrees C, the values of blood pressure, pulse rate and rectal temperature were significantly higher than those at 30 degrees C. Correlation between blood pressure and rectal temperature was significant, and blood pressure increased with rectal temperature dependently. The values of the indirect measurement were close to the values measured directly, and these correlations were highly significant. Thus, we showed the effects of temperature for indirect blood pressure measurement. This tail-cuff apparatus could measure the accurate value of indirect blood pressure without thermal stress at 30 degrees C. PMID- 1915601 TI - Central effects of yohimbine on copulatory behavior in aged male rats. AB - It is well known that yohimbine has a history of popular use because of its supposed aphrodisiac properties. The present study was done to determine whether yohimbine can modify the copulatory behavior of aged male rats. Adult male rats of the Wistar-Imamichi strain, 52 weeks of age and weighing 600-650g, were injected intracerebroventricularly with yohimbine hydrochloride (5, 10 micrograms/10 microliters/rat) or vehicle. Each male was then given the opportunity to mate with a receptive female for 30 min after administration of yohimbine or vehicle. Yohimbine produced significant decreases in the latency to initial mounting and significant increases in the number of mountings. However, there was no ejaculation in the yohimbine-and vehicle-treated males. This study is the first to clearly establish an important modulator of sexual arousal for yohimbine in aged male rats. PMID- 1915602 TI - [The diurnal changes in behaviors on laboratory beagle dogs]. AB - Diurnal patterns of food and water intakes, fecal and urine outputs, and locomotive activity were observed on beagles for three days continuously. They were kept individually in cages at temperature 21-23 degrees C, humidity 40-70% with a light time 7:00-19:00. The results showed that food and water intakes, and locomotive activity have diurnal patterns. Fecal and urine outputs have not diurnal patterns, but times of fecal and urine outputs is similar in many animals. The results suggest that physical condition is shown by quantitative values of behaviors, and sensitivity of diagnosis is raised by recognition of their diurnal patterns. PMID- 1915603 TI - Pyrogenic responses of the pika, Ochotona rufescens rufescens. AB - In 3-month-old male and female pikas, Ochotona rufescens rufescens, reared at an ambient temperature of 25 degrees C, the mean within-day body temperature was 39.2 degrees C without significant variance. At an ambient temperature of 35 degrees C it increased markedly in males while decreased slightly at 5 degrees C. The pikas showed lower sensitivity than Japanese white rabbits to a pyrogenic E. coli endotoxin. PMID- 1915604 TI - Pink-eyed dilution, a coat color mutation in the Japanese field vole (Microtus montebelli). AB - Inheritance of dilute coat color with pink eye in the Japanese field vole (Microtus montebelli) was investigated by mating of the dilute mutant with a normal agouti vole and a white vole. As the results, it was cleared that an autosomal recessive gene p is responsible for the pink-eyed dilution in M. montebelli. PMID- 1915605 TI - Spermatic granuloma in the epididymis of a beagle dog. AB - Pathological examination of a 9-month-old beagle dog revealed the epididymal spermatic granuloma. Grossly, a white nodule was observed in the cauda epididymis on the right side. Microscopically, there were numerous spermatozoa in the center of granuloma, surrounded by a wall of macrophages, fibroblasts, plasma cells, lymphocytes, neutrophils and giant cells. Furthermore, many macrophages containing IgG were observed in the center of granuloma. PMID- 1915606 TI - Tissue culture study on Mongolian gerbil's (Meriones unguiculatus) malignant melanoma. AB - We tried to culture melanoma cells from a Mongolian gerbil's (Meriones unguiculatus) malignant tumor. In primary culture, most of cells have abundant melanin granules in their cytoplasm. Melanin granules decreased through 5 to 15 serial passages and disappeared after 15 th passage. The morphology of the cells varied from spindle to large polydendritic cells. Although typical melanin granules were not seen when the cells were stained by Masson-Fontana method, the cells were positive for DOPA reaction. Electron microscopically, most of the cells have well-developed Golgi apparatus and rough-surfaced endoplasmic reticulum with dilated cistern, and premelanosome-like granules were frequently observed in their cytoplasm. PMID- 1915608 TI - Permanent marking of colored mice using dry ice. AB - Freeze marking, using dry ice, was successfully applied to colored mice for permanent, individual, identification. By this method, a 5-8 mm piece of dry ice is pressed against the skin of mice for 10 seconds. About 3 weeks after this treatment, spots of white hair growing at the site of treatment became recognizable to the naked eye, and allowed permanent identification of individual animals thereafter. The white spots were very clear in colored mice, and greatly facilitated animal identification as compared to conventional marking methods. Treatment of the animals with dry ice for 10 seconds has no discernible effects on the site of the treatment or the general condition of the animals. PMID- 1915607 TI - Effect of starvation and refeeding on the circadian rhythms of hematological and clinico-biochemical values, and water intake of rats. AB - We investigated the effect of starvation for 24 hr and subsequent refeeding for 12 hr on the circadian rhythms of 39 hematological and clinico-biochemical parameters, and water intake of F344 rats. The rats scarcely drank any water during the starvation period, but subsequently their intake of water were normal, even in the light period. During starvation, 12 parameters such as serum levels of alkaline phosphatase activity and PaCO2 decreased with time-related and time related increases of 8 parameters such as the erythrocyte count and cholinesterase activity. During refeeding for 12 hr, almost all these biochemical parameters were normalized, but none of the hematological values except the leukocyte count returned to normal levels. Starvation and refeeding had little affect on the circadian rhythms of others. PMID- 1915609 TI - [Periovulatory time courses of serum LH in the Japanese monkey (Macaca fuscata)]. AB - Serum LH, E2-17 beta and progesterone concentration were measured in 16 cycles of 15 female Japanese monkeys. Three of the 16 cycles were ascertained to be anovulatory. Ten of the 13 ovulatory cycles showed LH peaks varying from 25 to 280 ng/ml. However, in remaining 3 cycles, LH peak could not be determined, probably because of a lag of blood-sampling schedule. E2-17 beta peaks were detected 0-30 hrs before LH peak in 8 cycles, but 13 or 20 hrs after LH peak in 2 cycles. Time-intervals from LH peak to ovulation ranged 0-47 hrs 30 min. No correlation was detected between concentrations of LH and progesterone in the luteal phase. PMID- 1915610 TI - Spontaneous leukemia occurring in aged Slc: Wistar rats and its transplantation into rats. AB - Spontaneous leukemia occurred in 36% of a group of 39 aged Slc: Wistar rats, which ranged in age at death from 99 to 123 (average age: 114) weeks old. The leukemic rats showed hemolytic anemia, jaundice and leukocytosis (21,000 to 360,000/mm3). Macroscopically, they were characterized by splenomegaly and hepatomegaly. The leukemia cells were rich in basophilic cytoplasm containing eosinophilic granules. Their nuclei were oval and occasionally revealed mitotic figures. These leukemia cells were consistently transplantable into both Slc: Wistar and F 344/NSlc rats. In the transplanted cases, the latency and survival periods were prolonged in proportion to decreases in the inoculated cell dose. PMID- 1915612 TI - Orthodontics in the year 2000. PMID- 1915611 TI - [A three-dimensional computerized reconstruction of the rectum, anus and surrounding muscles of the rat fetus at the 20th gestation day]. AB - Using fetuses of Wistar/I rats on the 20th gestation day. We designed a three dimensional computerized reconstruction of the rectum, anus and the surrounding muscles. The tissues were fixed in Bouin's solution sagittally sectioned serially were stained with hematoxylin-eosin. Light microscopic pictures at 40 x magnification were subjected to the analysis using a three-dimensional image processing system, consisting of a drum-scanner, a general purpose computer (Micro VAX II), and a color image processor. The results showed that this system clearly reconstructed the three-dimensional image of the rectum, anus and the surrounding muscles and suggested the presence of the puborectal muscle sling. PMID- 1915613 TI - Face height and tooth eruption in adults--a 20-year follow-up investigation. AB - A longitudinal roentgen cephalometric investigation of vertical craniofacial and dentoalveolar changes during 20 years of adulthood, was performed in 15 men and 15 women. Two lateral cephalograms taken at the average ages 25 and 45 years, were available of each subject. Skeletal and dental changes were described by 13 linear and four angular cephalometric measurements. The analysis of the linear variables showed that total anterior face height increased by 1.60 mm on average. Approximately one-fifth of this increase occurred in the upper and four-fifths in the lower face. In the dentoalveolar region, significant increments of all dimensions except overjet and overbite were found, indicating an eruptive movement of the teeth and a vertical development of their investing tissues. The analysis of the angular measurements showed that posterior rotation of the mandible and uprighting of the upper incisors had occurred during the period of investigation. PMID- 1915614 TI - Surface resorption following two forms of rapid maxillary expansion. AB - Rapid maxillary expansion (RME) is a useful orthodontic technique for correction of posterior cross-bite of skeletal origin. The aim of the present study was to compare the frequency and nature of root resorption in premolars subjected to RME by means of either a tissue-borne, fixed split acrylic (Haas) palatal expansion applicance, or an all-wire framework appliance. Another factor examined was the relationship between the pattern of resorption and the duration of the retention period. RME was performed on five patients using the fixed split acrylic appliance and on four patients with the all-wire framework appliance. Following the transverse expansion, two upper and two lower premolars were extracted and processed for histological examination. Root resorption was found mainly on the buccal surfaces of all maxillary premolars. The resorption lacunae covered more of the root surface in premolars treated with an all-wire framework appliance compared to premolars treated with the acrylic expansion plate. The largest resorption areas were found on teeth extracted shortly after the expansion period and the smallest on premolars retained for a relatively longer period. Mandibular premolars showed neither buccal nor lingual resorptions. It was concluded that maximum anchorage of the expansion device, using the tissue-borne acrylic appliance, seems preferable in order to minimize the incidence of buccal surface root resorption. A longer post-treatment observation time is needed in order to draw more specific conclusions regarding the healing process of the damaged root surface. PMID- 1915615 TI - Second messengers: regulators of mechanically-induced tissue remodelling. AB - One of the most intriguing aspects of tissue reaction to mechanical forces such as in orthodontic tooth movement is the transduction of force into a meaningful cellular response. The behaviour of all eukaryotic cells is modulated by internal signalling systems which translate a wide array of external stimuli such as hormones or mechanical forces, into a very narrow range of internal signals (second messengers). Classically, the second messenger associated with mechanical force transduction is adenosine 3'5' cyclic monophosphate (cAMP); since it was virtually the only second messenger understood in any detail from 1960 to the late 1970s this is hardly surprising. A great deal more is now known about cell signalling mechanisms and for various reasons outlined in this review, the assumption that cyclic AMP is the sole messenger system in the transduction of mechanical forces is no longer tenable. PMID- 1915616 TI - The effect of osseointegrated implants on the dento-alveolar development. A clinical and radiographic study in growing pigs. AB - In an attempt to study the effect of osseointegrated implants on vertical dentoalveolar development, six growing pigs of the Pigham strain were used, one of them randomly selected as a control. The test pigs received four fixtures each, three in the lower jaw and one in the upper. The fixtures were placed in areas where different patterns of the dento-alveolar development were expected. The clinical and radiographic findings have clearly shown that the implants do not behave like normal erupting teeth during the development of the dentition. Neither do the fixtures move together with the adjacent teeth, but behave more like ankylosed teeth. PMID- 1915617 TI - The efficacy of two-stage titanium implants as orthodontic anchorage in the preprosthodontic correction of third molars in adults--a report of three cases. AB - Orthodontic movement of teeth is often required to satisfactorily treat a variety of oral rehabilitation problems. Considerable limitations in the clinical application of orthodontic treatment may result from the lack of teeth suitable for anchorage. Three patients with edentulous posterior segments are presented illustrating how implants can be utilized for preprosthodontic correction of impacted third molars rendering them suitable as bridge abutments. The patients have been followed for 8-10 years. Two-stage titanium implants were used as orthodontic anchorage as no dental anchorage was available. Edgewise orthodontic mechanics were used to move the third molars mesially with forces up to 2.5 N (about 250 g). No movement of the implants occurred and they were radiologically and clinically intact at the end of the orthodontic loading and were, therefore, subsequently used as bridge abutments. PMID- 1915618 TI - Bond strengths of five different ceramic brackets: an in vitro study. AB - The purpose of this investigation was to compare the bond strengths to enamel obtained in shear/peel and tensile/peel modes of testing using five different ceramic brackets and two different light-cured composites. The site of failure was also examined. Shear/peel bond strength was significantly affected by adhesive type, with Heliosit having higher mean bond strengths than Prismafil. Bond strength was significantly affected by bracket type; the highest mean bond strength in both tests being attained using Transcend with Heliosit. All brackets resisted shear/peel forces better than tensile/peel forces. High bond strengths are associated with an increased incidence of bracket and enamel fractures with Transcend and Starfire. PMID- 1915619 TI - A comparison of shear bond strengths between new and recycled ceramic brackets. AB - The recycling of 'used' ceramic brackets in the orthodontic surgery has been previously described. The present study investigated the shear bond strength of both recycled and new ceramic brackets. The mean shear bond strengths of the new and recycled ceramic brackets were 259.7 +/- 88.2 N and 187.2 +/- 60.8 N, respectively. Although significantly lower (P less than 0.01), the bond strength of recycled ceramic brackets appeared to be clinically adequate. There appeared to be little difference in the variation in bond strength between the new and recycled ceramic bracket group. Our results showed that the site of bond failure depended on the magnitude of bond strength. Scanning electron micrograph examination of the failure sites showed enamel fracture in one sample where the bond strength was extremely high. PMID- 1915620 TI - Effects of age, gender, and body size on nasal cross-sectional area in children. AB - The long-term goal of this research is to define the dimensions of nasal airway adequacy in children. Nasal airway size and variables associated with growth were assessed in 138 healthy children aged 7-15 years. The pressure-flow technique (Warren, 1984) was used to calculate the smallest cross-sectional area of the nasal airway. Mean nasal area was 0.38 +/- 0.12 cm2 for 7-9-year-olds, 0.40 +/- 0.13 cm2 for 10-12-year-olds, and 0.46 +/- 0.16 cm2 for 13-15-year-old children, the effect of age being statistically significant. Nasal airway size did not vary systematically with body size nor was there any clear difference between girls and boys. We conclude that age should always be considered when assessing the status of the nasal airway in children and adolescents. PMID- 1915621 TI - Measurement of intra-oral negative air pressure during dummy sucking in human newborn. AB - Non-nutritive sucking on a dummy was studied in 23 clinically normal full-term infants with a mean gestational age of 40 weeks (SD 1.5). The intra-oral negative air pressure was measured by a miniature air pressure transducer inside a commercial dummy. The sucking pattern in these infants was always composed of periodical changes between sucking burst and interburst periods with a mean rate of 5.3 (SD 1.6) bursts per minute. The mean rate of sucks within a sucking burst was 1.7 (SD 0.2) sucks/sec. The mean value of maximum intra-oral negative air pressure among newborn was 58 mbar (SD 14.6) during dummy sucking. During interburst periods the negative air pressure remained at a mean value of 8.4 mbar (SD 5.8). PMID- 1915622 TI - Effect of bracket and wire composition on frictional forces. AB - Previous work on friction has considered movement of single teeth along an archwire. The aim of this investigation was to consider friction in buccal segment attachments during overjet reduction involving sliding mechanics. A buccal segment model was constructed to compare friction in steel and ceramic brackets, using steel and nickel titanium wires of two sizes along with a new experimental polymeric wire. The results indicate that friction during overjet reduction is minimized by using larger dimension rectangular wires and by using steel rather than nickel titanium. Comparing steel with ceramic brackets in series, the latter show greater frictional resistance, but only when used with the smaller rectangular wires. The combined effect of environment, ligation, bracket, and archwire significantly reduced the difference. Clinically, there may, therefore, be little to choose between steel and ceramic brackets in the buccal segments, with wire choice as determined by tooth displacement being more important. Comparison of the results with those obtained using single brackets illustrates the problems of interpreting results from friction experiments. The polymeric archwire in its present form was found to be unsuitable for use in orthodontics. PMID- 1915623 TI - An extra X chromosome effect on craniofacial morphogenesis in men. AB - A comparative study of the craniofacial complex in men with an extra X chromosome, and normal male and female individuals was carried out using cephalometric radiography. The anterior cranial base, anterior and posterior facial height, maxillary base and ascending ramus were found to be significantly decreased in men with Klinefelter syndrome when compared to the male control group. Significant differences in the lengths of mandibular base and posterior cranial base were not found. When compared to the female control, all structures examined were significantly increased, except for the maxillary base. PMID- 1915624 TI - The relevance of genetic susceptibility in Graves' disease and immune thyroiditis. AB - It has been known for a long time that there is an increased incidence of Graves' disease and immune thyroiditis in certain families. Genetic research of this disease has shown that it is most probably transmitted in a multifactorial way, i.e. that environmental as well as genetic factors play a role in the genesis of the diseases. This hypothesis is supported by the fact that the rate of concordance is maximally 50% in identical twins. The following model of threshold values is conceivable for the formal genetics of Graves' disease and immune thyroiditis: the diseases break out whenever the sum of environmental (viruses, bacteria, iodine excess, hormones, stress) and genetic (MHC and non MHC restricted) factors is higher than a given threshold. One of the major genes influencing the genesis of the diseases seems to be HLA-DR3 (or a closely linked gene in strong linkage disequilibrium). If this gene is present, fewer environmental factors are possibly needed. PMID- 1915625 TI - Thyroid-specific antigens in Basedow's disease. AB - All three major thyroid-specific auto-antigens, namely Tg, TPO and the TSH receptor, have now been cloned. Of greatest significance in the pathogenesis of Basedow's disease is the TSH receptor. It is anticipated that in the coming years this accomplishment by a number of laboratories will lead to major advances in our understanding of this disease. Opportunities are now available to study the molecular mechanisms underlying Basedow's disease, and we will emerge from a phase of descriptive investigation. It is quite possible that before the 200th anniversary of Basedow's description of this disease, specific immunotherapy will permit the treatment or prevention of Basedow's disease, without requiring ablation of the thyroid, or medicinal blockade of thyroid hormone synthesis while hoping that the disease will remit spontaneously. PMID- 1915626 TI - The TSH receptor in autoimmune Basedow's disease. AB - The cloning approaches of the past two years have opened new doors to the pursuit of our understanding Basedow's disease. The cloning of the TSH receptor is the most dramatic step; nevertheless, all the proteins mentioned in the following appear to be important molecules in the bioactivity of the thyroid cell and are implicated as autoantigens. PMID- 1915627 TI - Structure of the TSH receptor. PMID- 1915628 TI - Autosomal dominant inheritance of the tendency of develop thyroid autoantibodies. PMID- 1915629 TI - Antiidiotypic antibodies against anti-TPO antibodies in sera of patients with autoimmune thyroid disorders. PMID- 1915631 TI - Expression of iodothyronine deiodinase in cultured thyroid cells. PMID- 1915630 TI - Interleukin-6 is not a second mediator of interleukin-1 induced suppression of thyroid function in cultured human thyrocytes. PMID- 1915632 TI - Some unanswered questions in thyroid-related ophthalmopathy. PMID- 1915633 TI - Nature of a 64 kDa eye muscle membrane autoantigen as determined from immunoprecipitation and immunoblotting. PMID- 1915634 TI - Autoantibodies to eye muscle and orbital fibroblasts in the pathogenesis of thyroid-associated ophthalmopathy. PMID- 1915635 TI - Eye-muscle membrane antibodies in autoimmune orbitopathy. PMID- 1915636 TI - Modulation of HLA-DR expression on retroocular fibroblasts from patients with active thyroid-related ophthalmopathy: in vitro effects of agents used in the management of hyperthyroidism and ophthalmopathy. PMID- 1915637 TI - Some immunological correlations between thyroid pathology and ophthalmopathy. AB - Hormonal and immunogenetic investigation of patients with ophthalmopathy in the presence of thyroid pathology and without it made it possible to come to a conclusion of the independence of both diseases. Immunological markers of thyroid pathology in the presence of ophthalmopathy are noted less frequently than in thyroid diseases without ophthalmopathy. The latter is characterized by the presence of specific autoantibodies to eye muscle membranes in the patients' sera. The presence of antithyroid antibodies increases the probability of appearance of antibodies to eye muscles and therefore can be regarded as a risk factor of ophthalmopathy. PMID- 1915638 TI - Differential diagnosis of hyperthyroidism. PMID- 1915639 TI - Why do we need the ophthalmologist? PMID- 1915640 TI - Ophthalmological diagnosis in autoimmune orbitopathy. PMID- 1915641 TI - Antithyroid drug treatment of von Basedow's disease: results from a multicenter study. PMID- 1915642 TI - Effect of therapy duration and low and highly dosed thiamazole treatment in Basedow's-Graves' disease. PMID- 1915644 TI - Methimazole and agranulocytosis--clinical study. AB - The paper deals with agranulocytosis as one of the side effects of methimazole. The analysis of 7 cases allows some conclusions in respect to prevention, early detection and treatment of this rare but serious complication. PMID- 1915643 TI - Adverse effects related to antithyroid drugs and their dose regimen. PMID- 1915645 TI - Radioiodine treatment of Basedow's disease: interference and influence factors, risk estimation. AB - I-131 treatment of Basedow's disease is effective and safe. Relatively high energy doses to the thyroid in the range of 150-200 Gray are needed in endemic goiter areas, where immunogenic hyperthyroidism may coincide with functional autonomy. Induction of euthyroidism by low doses of antithyroid drugs (methimazole, carbimazole) before I-131 treatment prevents complications and has no significant influence on outcome of I-131 therapy. As compared to alternative therapeutic modalities, the risks of I-131 are low. PMID- 1915646 TI - Results of 131I theory for 2,000 thyrotoxic patients: do the effects depend on the dose? PMID- 1915647 TI - Surgery for immunogenic hyperthyroidism. PMID- 1915648 TI - Treatment of hyperthyroidism with potassium iodide. AB - Potassium iodide was given to 17 cases of Basedow's disease in comparison to 12 normal controls for 5 weeks. In the thyrotoxic patients, the maximum decrease in serum T3 and T4 levels was observed 2 and 3 weeks, respectively, but in some cases remained normal even at 5 weeks. The euthyroid persons showed a small decrease in T4 and T3 and an increase in serum TSH. PMID- 1915649 TI - Nonsteroid immunosuppressants in endocrine orbitopathy. PMID- 1915650 TI - Glucocorticoid therapy of Graves' ophthalmopathy. PMID- 1915651 TI - The role of plasmapheresis in Graves' ophthalmopathy. PMID- 1915652 TI - Role of orbital radiotherapy in the treatment of Graves' ophthalmopathy. PMID- 1915653 TI - Pitfalls associated with orbital decompression for thyroid-related orbitopathy. PMID- 1915654 TI - Visual evoked potentials in Basedow's ophthalmopathy before and after orbital decompression or retrobulbar irradiation. AB - VEP are an objective and a more sensitive sign of optical neuropathy in Graves' ophthalmopathy than is visual acuity. A correlation exists between VEP and the changes in the external eye muscles as visualized on CT scans. VEP should always be registered if CT changes are present. Improvement of optic neuropathy as evaluated from VEP seems to be remarkably infrequent. PMID- 1915655 TI - Total thyroidectomy in the treatment of Basedow's ophthalmopathy. AB - Four patients in the age 42-63 (3 females and 1 male) with Basedow's disease and hyperthyroidism were investigated. Visual changes were classified to the IV group of American Thyreologic Society's classification. A total thyroidectomy was performed when status of euthyreosis has been obtained. Check examinations were carried out 6, 12 and 18 months after surgery. It has been confirmed that total thyroidectomy performed in patients with thyroid ophthalmopathy leads to reduction of infiltrative changes in the orbit. However, this can be stated not earlier than 12 months after surgery. PMID- 1915656 TI - Binding activity of glucocorticoid receptors after heat shock. AB - The response of glucocorticoid receptors (GR) to heat was measured by the change in ligand binding activity both in control cells and in cells made tolerant to heat by a prior mild heat exposure. The study was prompted by earlier data showing that one of the heat shock proteins (HSP90) is an essential component of the GR complex and that treatment of mammalian cells with hydrocortisone induces resistance to heat damage. The GR rapidly loses binding activity after commencement of heating. There is a 50% loss of activity after 4 min at 45 degrees C, 8 min at 44 degrees C, or 17 min at 43 degrees C. The reduction in binding is due mainly to a reduction in affinity of binding to the ligand. The ability to bind glucocorticoid recovers quickly after heat treatment. Activity returns to levels 60-80% of normal by 2 h after a heat treatment that initially reduces binding to less than 20% of normal. However, complete restoration of binding activity takes approximately 3 days. The recovery of binding activity does not require protein synthesis. Pretreatment of cells with hydrocortisone, using conditions that induce heat resistance, reduces the activity to 10-20% of control, but residual receptors display a heat sensitivity similar to that of control cells. There was evidence for a limited degree of protection of GR from heat damage in thermotolerant cells. PMID- 1915657 TI - Spreading of mouse fibroblasts on the substrate with multiple spikes. AB - Mouse embryo fibroblasts were cultivated on special substrates with discontinuous surfaces. The substrates were silicon plates with multiple vertical (65-90 microns height) spike-like silicon microcrystals evenly distributed on the plate surfaces. It was shown that the cells were successfully spread and flattened on these substrates. The spread cells formed several discrete attachment zones at the tops and side surfaces of the spikes; these zones were separated from one another by distances considerably greater than the diameter of the unspread cell. At early stages of spreading the unspread cells attached to the tops of single spikes and extended long filopodia attached to the distant spikes. At later stages the lamellae were formed between the filopodia: probably these filopodia served as guidelines for extension of lamellae and progressive cell spreading. These experiments demonstrated that continuity of substrate surface is not a necessary condition for advanced cell spreading. PMID- 1915659 TI - Characteristics of an infinite life span diploid human fibroblast cell strain and a near-diploid strain arising from a clone of cells expressing a transfected v myc oncogene. AB - Diploid human fibroblasts were transfected with a plasmid carrying a v-myc oncogene linked to the neo gene or with a vector control carrying a neo gene. Drug-resistant clones were isolated and subcultured as needed. All populations went into crisis and eventually senesced. But while they were senescing, viable appearing clones were noted among the progeny of a transfected population that expressed the v-myc oncogene. After several months, these cells began replicating more rapidly. Karyotype analysis indicated that they were clonally derived since all of them had 45 chromosomes, including 2 marker chromosomes. This cell strain was designated MSU-1.1. Similar analysis showed that cells from an earlier passage were diploid. These cells were designated MSU-1.0. Both strains have undergone more than 200 population doublings since their siblings senesced, without any change in chromosome complement. Both strains express the v-myc protein and have the same integration site for the transfected v-myc and neo genes. The MSU-1.0 cells cannot grow without exogenously added growth factors. The MSU-1.1 cells grow moderately well under the same conditions and grow to a higher saturation density than MSU-1.0 cells. Since the chance of human cells acquiring an infinite life span in culture is very rare, the data suggest that MSU-1.1 cells are derived from MSU-1.0 cells. The expression of v-myc is probably required for acquisition of an infinite life span, since this phenotype did not develop in populations not expressing this oncogene. However, expression of v-myc is clearly not sufficient, since all of the progeny of the clone that gave rise to the MSU-1.0 cells expressed this oncogene, but the vast majority of them senesced. PMID- 1915658 TI - Retinol-binding protein and transthyretin expressed in HeLa cells form a complex in the endoplasmic reticulum in both the absence and the presence of retinol. AB - To establish a suitable experimental system for studies of the interaction of retinol-binding protein (RBP) with transthyretin (TTR) we have expressed the corresponding cDNAs in HeLa cells. To investigate whether complex formation might occur already in the endoplasmic reticulum (ER), the C-terminal ER retention signal, KDEL, was attached to TTR. The tetrameric TTR-KDEL fusion protein was retained in the ER of HeLa cells. When RBP was co-expressed with TTR-KDEL, RBP was retained intracellularly. A cDNA-encoding purpurin, a protein which is 50% identical to RBP, was then expressed together with TTR-KDEL. Purpurin was not retained intracellularly and did not bind to TTR coupled to Sepharose. The effect of the vitamin A status on the secretion of TTR and RBP was examined. While TTR expressed alone was not retained intracellularly, TTR was retained in vitamin A deficient cells when co-expressed with RBP. Addition of retinol stimulated rapid secretion of both proteins. These results demonstrate that TTR can form a complex with RBP in the ER. The data suggest that RBP and TTR are secreted as a complex. PMID- 1915660 TI - Micromanipulation of mitotic chromosomes in PTK2 cells using laser-induced optical forces ("optical tweezers"). AB - To study the potential use of optical forces to manipulate chromosome movement, we have used a Nd:YAG laser at a wavelength of 1.06 microns focused into a phase contrast microscope. Metaphase and anaphase chromosomes were exposed while being monitored by video microscopy. The results indicated that when optical forces were applied to late-moving metaphase chromosomes on the side closest to the nearest spindle pole, the trapped chromosomes initiated movement to the metaphase plate. The chromosome velocities were two to eight times the normal rate depending on the chromosome size, geometry, and trapping site. At the initiation of anaphase, a pair of chromatids could be held by the optical trap and kept motionless throughout anaphase while the other pairs of chromatids separated and moved to opposite spindle poles. As a result, the trapped chromosome either was incorporated into one of the daughter cells or was lost in the cleavage furrow, or the two chromatids eventually separated and moved to their respective daughter cells. If the trap was removed at the beginning of anaphase B, the chromosome moved back to the poles. Our experiments demonstrate that the laser-induced optical force trap is a potential new technique to study noninvasively the mitotic spindle of living cells. PMID- 1915661 TI - Arrangement of kinetochore proteins and satellite DNA in neuronal interphase nuclei: changes induced by gamma-aminobutyric acid (GABA). AB - Discrete chromatin domains occupy specific nuclear compartments in neuronal interphase nuclei. Nuclear rotation, defined as the motion of interphase chromatin domains, has been proposed to function in the placement of specific chromatin domains to nuclear compartments which are appropriate to the physiological state or the state of differentiation of the cell. Rates of this chromatin motion may be increased by agents, including gamma-amino butyric acid (GABA), which may cause changes in gene expression. To test whether GABA also causes a spatial rearrangement of specific chromatin domains, the three dimensional distribution of kinetochores in nuclei of mouse dorsal root ganglion neurons was determined by immunofluorescence. In addition, centromeric satellite DNA sequences were localized by in situ hybridization using a biotinylated mouse satellite DNA probe followed by immunofluorescence. Kinetochores occurred in clusters, associated with nucleoli or in intermediate nucleoplasmic regions, between the nucleolus and the nuclear membrane. Clusters of satellite DNA sequences were found either associated with nucleoli or throughout the nucleoplasm. Strikingly, nucleoplasmic kinetochores consistently occupied a 5 microns distance from the nuclear center, representing 70% of the spherical nuclear radius. Exposure of neurons to GABA induced a significant reorganization of kinetochores which may represent movement of chromosomes to alternate nuclear compartments to accommodate a new transcriptional state. PMID- 1915662 TI - Ionophore-induced apoptosis: role of DNA fragmentation and calcium fluxes. AB - Two ionophores specific for K+, valinomycin and beauvericin, induce a type of cell death very similar to apoptosis due to tumor necrosis factor (TNF alpha). Both ionophores cause cytolysis accompanied by internucleosomal DNA fragmentation of the dying cell into units of 200 base pairs. Morphologically, the cell death appears to consist of a mixture of nuclear apoptotic changes and cytoplasmic necrotic changes. As in the case for TNF alpha-mediated death, metabolic inhibitors have no effect on the course of cell death, but DNA fragmentation and cytolysis are decreased by the endonuclease inhibitor, zinc. Beauvericin and valinomycin trigger an increase in the cytoplasmic calcium concentration, most likely due to release of calcium from intracellular stores, and chelation of cytoplasmic calcium with quin-2 inhibits DNA fragmentation. Thus, these ionophores set off apoptosis through a calcium-activatable endonuclease, suggesting that other nonphysiological toxins might also cause apoptosis through their ability to indirectly elevate the cytoplasmic calcium concentration, without the need to invoke specific surface receptors. PMID- 1915663 TI - Apolipoprotein A-1 expression is resistant to dimethyl sulfoxide inhibition of myogenic differentiation. AB - Primary cultures of chick embryonic muscle (CEM) were analyzed for the differential expression of a 26-kDa protein during myogenesis. We have identified this 26-kDa protein as apolipoprotein A-1 (Apo A-1), the major protein of serum high density lipoprotein particles. Apo A-1 was expressed in a pattern temporally similar to those of muscle-specific proteins, by myoblasts at very low levels, and by myotubes at high levels. The half-life of Apo A-1 in CEM cell homogenates was 23 min. This fast turnover rate appeared to be due to the secretion of Apo A 1 into the culture medium. To further characterize the relationship of Apo A-1 expression and myogenic differentiation, CEM cultures were treated with dimethyl sulfoxide (DMSO). In the presence of 2% DMSO, myotubes exhibited an atrophied morphology and an inhibition of the synthesis and accumulation of muscle-specific sarcomeric proteins. During recovery from DMSO treatment, the expression and accumulation of muscle-specific proteins returned to high levels. In contrast, the rates of synthesis and secretion of Apo A-1 in control, DMSO-treated, and DMSO-recovered CEM cells were nearly equivalent. These results indicate that the expression of Apo A-1 is not strictly linked to the expression of muscle-specific sarcomeric proteins in skeletal muscle and suggest that independent, or additional regulatory mechanisms exist which modulate Apo A-1 expression during myogenesis. PMID- 1915664 TI - Differential expression of poly(ADP-ribose) polymerase and DNA polymerase beta in rat tissues. AB - The activities of two DNA repair-related enzymes, poly(ADP-ribose) polymerase and DNA polymerase beta, and their mRNA levels were measured in 17 tissues of Wistar rats. A large variety in enzyme activity values could be detected in the tissues examined; the highest levels of activity for both enzymes were found in the testis. A good correlation between poly(ADP-ribose) polymerase activity and the level of the transcript of the gene coding for the enzyme was observed in many tissues. A less satisfactory correlation could be evidenced for DNA polymerase beta. The almost parallel amounts of the mRNAs for poly(ADP-ribose) polymerase and DNA polymerase beta in the tissues examined suggest a possible coexpression of the genes coding for these enzymes. Additional studies have been carried out in testis and liver by immunohistochemical techniques and by in situ hybridization analyses. While in the testis the spermatocytes were shown to contain both enzymes and their transcripts, in other types of cells this could not be observed. In the liver mRNAs and enzymes were only found in 20% of the hepatocytes. This may in part explain both the low levels of the mRNAs and the modest activities of the two enzymes in that tissue. PMID- 1915665 TI - Uptake of hyaluronan in hepatic endothelial cells is not directly affected by endotoxin and associated cytokines. AB - The uptake of hyaluronan (HYA) labeled with 3H in its acetyl group was measured in cultured liver endothelial cells from normal rats and from rats previously treated with sublethal doses of Escherichia coli endotoxin (ET). Replicate cultures were also exposed to recombinant human tumor necrosis factor-alpha (TNF alpha), interleukin-1 (IL-1) or interferon-gamma for 1 to 3 h before the measurement of hyaluronan uptake. Under all conditions, HYA was absorbed by endothelial cells at rates consistent with receptor-mediated absorption. In cells exposed to HYA 20 h after isolation, rate of uptake was less than half the rate in cells exposed 6 or 7 h after isolation. Cellular uptake of HYA was neither reduced nor enhanced by any of the treatments with cytokines. Prior exposure of the cell donors to ET caused a three-fold increase in their plasma HYA but did not alter the subsequent rate of cellular HYA uptake in vitro, either with or without added treatment with TNF-alpha or IL-1. It was concluded that the elevation of plasma HYA caused by septicaemia or by the experimental administration of ET or TNF-alpha cannot be attributed to direct interference with HYA receptors on hepatic endothelial cells. PMID- 1915666 TI - Inhibition of phorbol ester-induced cell activation in microgravity. AB - T lymphocytes and monocytes were exposed to microgravity and activated to produce interleukin 2 and interleukin 1, respectively. When Jurkat T cells were triggered with monoclonal antibodies directed against the CD3/T cell receptor complex in the presence of THP-1 monocytes used as accessory cells, cell-to-cell contacts took place in microgravity leading to normal production of interleukin 2 and interleukin 1, as compared to ground controls. In contrast, when cells were individually stimulated by soluble substances including a protein kinase C activating phorbol ester, the production of interleukin 1 and interleukin 2 was dramatically inhibited during microgravity exposure. This result indicates that microgravity may affect the cellular target of phorbol ester. PMID- 1915667 TI - Nuclear responses to protein kinase C signal transduction are sensitive to gravity changes. AB - A number of studies have suggested that gravity changes may influence mammalian cell growth and differentiation. To obtain insight in the molecular mechanisms underlying these effects, we have studied immediate early gene expression in response to activation of cytoplasmic signal transduction under microgravity conditions. In this paper we show that epidermal growth factor (EGF)- and 12-O tetradecanoyl-phorbol-13-acetate (TPA)-induced expression of the c-fos and c-jun protooncogenes is decreased in microgravity, while no effect of gravity changes was observed on A23187- and forskolin-induced expression of these genes. These decrease in c-fos expression was not due to delayed kinetics under microgravity. These results demonstrate that gravity differentially modulates distinctive signal transduction pathways. PMID- 1915668 TI - Identification and immunolocalization of calreticulin in pancreatic cells: no evidence for "calciosomes". AB - In the present study, we have shown that calreticulin is a major Ca(2+) sequestering protein in pancreatic microsomes. This protein is a peripheral membrane protein and could be extracted from the microsomal membrane with carbonate buffer at pH 11.4. Calreticulin was identified in the membrane fractions by immunoblotting with a specific antibody, by a 45Ca2+ overlay technique, and by NH2-terminal amino acid analysis of the purified protein. Immunocytochemical localization of calreticulin in pancreatic acinar cells and pancreatic fibroblasts showed that the protein is localized to the ER membranes in these cells. We were unable to detect calsequestrin or any calsequestrin-like proteins in the pancreas and found no evidence for the existence of large numbers of specialized, calreticulin-containing vesicles which could be an equivalent of the calsequestrin-containing calciosomes previously reported in this tissue. Purified pancreatic calreticulin binds Ca2+ with both a low and a high capacity (approximately 1 mol of Ca2+/mol of protein and approximately 20-23 mol of Ca2+/mol of protein). The concentrations of Ca2+ required for half-maximal saturation of the low and high capacity sites were approximately 4-6 microM and approximately 1.5 mM, respectively. We conclude that calreticulin, which is confined to the lumen of the ER, plays a major role in Ca2+ storage in pancreatic cells. PMID- 1915669 TI - Experimental autoimmune retinitis in the rat induced by immunization with rhodopsin: an ultrastructural study. AB - Experimental autoimmune retinitis induced by immunization with rhodopsin was investigated in the Lewis rat using transmission electron microscopy and light microscopy. The first signs of retinitis consisted of scattered infiltrations of lymphocytes and other mononuclear cells, predominantly in the inner nuclear layer and outer plexiform layer. Occasionally, some macrophages were detected in the photoreceptor cell layer. Eyes exhibiting a clinically moderate or severe inflammation contained areas of normal retina coexistent with mildly to severely inflamed foci. The central retina was more frequently affected than the peripheral area. In moderately inflamed foci, macrophages infiltrated the photoreceptor cell layer, damaging and eliminating its structures. Inflammatory cells penetrated the photoreceptor outer segment layer which remained unaltered so far in spite of a high serum anti-(rhod)opsin antibody titer. In stages of severe inflammation, massive infiltrations of macrophages and polymorphonuclear cells destroyed the photoreceptor cells focally, leaving the retinal pigment epithelium virtually unaffected. Adjacent to these foci the pigment epithelial cells sometimes exhibited increased numbers of phagosomes and swelling. The locations of the cell infiltrations and lesions in progressive stages of development suggest that the rod outer segments are the target for the autoimmune damage. The described patterns of inflammation were compared with those of previous studies using other animal species and inciting antigens. Especially in rhodopsin-induced retinitis, the blood-retina barrier at the level of the Bruch's membrane/pigment epithelium appears to be highly resistant to cytotoxic cells. The present observations are in agreement with the concept that the cellular immune response plays a major role in the pathogenesis of (rhod)opsin-induced retinitis. PMID- 1915670 TI - Choroidal and ciliary body blood flow analysis: application of laser Doppler flowmetry in experimental animals. AB - Laser Doppler flowmetry (LDF) measures the flux of red blood cells in a vascular network embedded in tissue. In the present report, choroidal and ciliary body blood flow was measured continuously using an LDF technique in pentobarbital anesthetized cats. Blood flow measurements were made from the choroid beneath the lateral and superior rectus muscles and from the surface above the ciliary body 2 3 mm posterior to the limbus. In some experiments, the sympathetic nerve to the eye was stimulated; in others, intraocular pressure (IOP) was monitored manometrically with a controlled saline infusion delivered into the anterior chamber to gradually elevate IOP. Norepinephrine (NE) and methacholine (MC) also were tested for their effects on choroidal blood flow when given intravenously and intra-arterially. Transient bilateral carotid artery occlusions produced a significant drop in blood flow, but flow did not decrease to zero probably due to collateral contribution of the vertebral circulation. Sympathetic nerve stimulation produced a frequency-dependent decrease in both choroidal and ciliary body blood flow with the latter exhibiting a lower threshold and a greater magnitude of effect. Gradual elevation of IOP produced a proportional decrease in choroidal blood flow. The level of intraocular pressure required to decrease blood flow was dependent on the existing ocular perfusion pressure. Both intravenous and intra-arterially administered NE produced dose-dependent decreases of choroidal blood flow despite graded increases of systemic arterial blood pressure. In contrast, MC produced dose-dependent increases of choroidal blood flow in conjunction with graded decreases of systemic blood pressure. The results of the present report demonstrate the validity of the LDF technique for performing continuous reading of blood flow changes in the choroid and ciliary body of experimental animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915671 TI - Angiotensin-like immunoreactive cells in the chicken retina. AB - The cellular distribution of Angiotensin II (ANGII) in the chicken retina was studied by immunocytochemical methods. Three different antibodies directed against ANGII revealed a distinct subpopulation of ANGII-positive amacrine cells. Their cell bodies were located in the innermost rows of the inner nuclear layer (INL). ANGII-positive cell bodies also were found in the ganglion cell layer (GCL). Faint labelling in the centre of the INL was visible, probably related to Muller cell bodies. Single ANGII-positive fibres, each arising from an amacrine cell body, ran to sublayer 3 or 5 of the INL, forming narrow plexi. In addition, small fibres connecting sublayer 3 with sublayer 5 could be observed. ANGII positive fibres could neither be detected in the optic nerve nor in the outer parts of the retina. Incubation of the tissue in ANGII or angiotensin I (ANGI) dissolved in Ringer solution prior to fixation, increased number and intensity of labelled cells and resulted in better labelling of sublayers 3 and 5 of the inner plexiform layer (IPL). Blockage of the conversion of ANGI to ANGII by adding captopril to the ANGI containing pre-incubation medium reduced the ANGII induced staining enhancement. All three ANGII-antibodies showed corresponding results. These results indicate that a subpopulation of amacrine cells contains angiotensin II in chicken retina. This subpopulation is apparently able to take up ANGII and ANGI, to convert ANGI to ANGII and to store ANGII. PMID- 1915672 TI - The phagocytosis of ROS by RPE cells is not inhibited by mannose-containing ligands. AB - We have examined the ability of mannose and the mannose-rich ligands, mannan and mannosylated BSA, to inhibit the phagocytosis of rod outer segments (ROS) by cultured rat retinal pigment epithelial (RPE) cells. Mannose, at concentrations up to 0.25 M, had no effect on either the binding or the ingestion of ROS. At concentrations above 0.25 M, the cells were rounded and showed detachment from the substrate, and phagocytosis was markedly inhibited. Neither mannan (2 mg ml 1), nor mannosylated BSA(0.8 mg ml-1), affected the phagocytosis of ROS. These results suggest that the phagocytosis of ROS is probably not mediated by a mannose receptor on the surface of the RPE cells. PMID- 1915673 TI - Identification of an S-antigen-like molecule in Drosophila melanogaster: an immunohistochemical study. AB - Vision is a highly complex process common to many vertebrate and invertebrate species. The visual system of Drosophila represents a valuable model in which to study this process since its chromosomal makeup has been well mapped and many mutants containing specific photoreceptor defects have been described. S-antigen is a well-characterized photoreceptor cell protein which plays a fundamental role in the visual process. In this study, we used a panel of four monoclonal antibodies (MAbs) specific for amino, mid and carboxy terminal amino acid sequences in S-antigen in order to examine S-antigen immunoreactivity in the Drosophila visual system. Two MAbs, MAb5C6.47 and MAbC10-C10, localized S-antigen to the retinules and ocelli. In contrast, MAbA2-G5 and MAbA9-C6 did not stain. The presence and strong antigenic similarity of an S-antigen homolog in Drosophila suggests that in both vertebrates and invertebrates S-antigen plays a major role in the regulation of the phototransduction of vision. PMID- 1915674 TI - Effects of long-term administration of HMG-CoA reductase inhibitors on cholesterol synthesis in lens. AB - The effects of long-term dosing with inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase on the rate of cholesterol biosynthesis were examined in the lens and liver of rats and hamsters. While both pravastatin and lovastatin inhibited incorporation of [14C]acetate into cholesterol in liver slices 2-4 hr after an oral dose, lovastatin, but not pravastatin, inhibited sterol synthesis in lens as well. At 24 hr after a single oral dose, cholesterol synthesis in livers from drug-treated animals was increased compared to controls. This induction of the cholesterol synthetic pathway was observed for both drugs in the liver but only for lovastatin in the lens. After 4 days of once-daily oral doses, synthesis in the lens was induced two to threefold by lovastatin but not by pravastatin. When the drug was included in the continuous diet for 4-5 days, lovastatin caused increases in cholesterol synthesis in the lens whereas lenses from pravastatin-treated animals were identical to controls. This was not a species-specific effect since a similar tissue selectivity was observed in the hamster. The increase in cholesterol synthesis in lenses observed in lovastatin treated rats was accompanied by an increase in the activity of HMG-CoA reductase enzyme. These studies demonstrate that non-selective HMG-CoA reductase enzyme inhibitors can inhibit cholesterol synthesis in the lens, and following this inhibition a marked induction in the cholesterol biosynthetic pathway develops in the lens and this induction is associated with an increase in HMG-CoA reductase enzyme activity. PMID- 1915675 TI - Changes in expression and distribution of lactate dehydrogenase isoenzymes in the developing chick retina. AB - We have investigated the expression and distribution of lactate dehydrogenase (LDH) isoenzymes in the developing and adult chicken retina. Non-denaturing polyacrylamide gel electrophoresis was used to follow the appearance and expression of the five main LDH isoenzymes in tissue homogenates. Immunohistochemistry was used to define the distribution of the aerobic heart type LDH and the anaerobic muscle type LDH in paraffin sections of embryonic and adult chick retina. The electrophoretic results show that the expression of the anaerobic isoenzyme increases in the retina as development proceeds. Immunoreactivity against the anaerobic isoenzyme localizes to the inner plexiform layer and other regions of the inner chick retina. The aerobic isoenzyme immunoreactivity is localized to the inner segments of the photoreceptor cells as well as the ganglion cell layer. Both antibodies bind weakly in other layers of the retina with the notable exception that the anaerobic protein does not localize in the photoreceptor cell inner segments. These results provide further evidence for the anaerobic nature of the adult inner retina. As retinal development proceeds, the expression of the anaerobic isoenzyme in the retina increases. PMID- 1915676 TI - Age-related cysteine uptake as rate-limiting in glutathione synthesis and glutathione half-life in the cultured human lens. AB - The study included human lenses of ages ranging from newborn to 92 years. Protein free reduced glutathione decreased 14-fold, whereas protein-free oxidized glutathione increased 2.6-fold with increasing age. L-Cyst(e)ine uptake g-1 lens of very old cultured lenses decreased 70% from that exhibited in newborn lenses, demonstrating a marked decline of L-cyst(e)ine uptake as a function of age. In these same lenses the synthesis of reduced glutathione (mumol g-1 lens) decreased 73% with age. It was concluded that the glutathione decrease observed in the aging human lens was associated with decreased uptake of L-cyst(e)ine, decreased glutathione synthesis and possibly an increase in protein-free oxidized glutathione. The high correlation of L-cyst(e)ine uptake and glutathione synthesis supports the hypothesis that L-cyst(e)ine uptake is a rate-limiting factor of glutathione synthesis in the intact human lens. By the use of buthionine sulfoximine, the half-life of glutathione was estimated to be 90 hr in the cultured human lens. PMID- 1915677 TI - The lenticular nucleus, light, and the retina. AB - Lenticular absorbance and retinal illumination are reviewed in the light of earlier observations showing that the nucleus rather than the lens as a whole is the main absorber of radiation. Corneal refraction is taken into account. Consideration is given to the Stiles-Crawford effect, and to the accumulation of lipofuscin in the retinal pigment epithelium which may be caused by illumination of the retina. PMID- 1915678 TI - Potassium-evoked responses from the retinal pigment epithelium of the toad Bufo marinus. AB - Changes in the apical and basal membrane potentials and the resultant changes in the transepithelial potential were recorded from the isolated retinal pigment epithelium of the toad Bufo marinus while the potassium concentration superfusing the apical membrane was changed. Lowering apical potassium caused an initial apically-generated hyperpolarization that increased the transepithelial potential which was usually followed by a delayed basally-generated hyperpolarization that decreased the transepithelial potential. Light evoked a similar pattern of apical and basal responses in a preparation of neural retina-retinal pigment epithelium choroid. The delayed basal hyperpolarization was accompanied by an apparent increase in basal membrane resistance, and was inhibited by adding the anion transport blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid or the metabolic inhibitor dinitrophenol to the solution superfusing the choroidal side of the retinal pigment epithelium (RPE). The results suggest that a change in the chloride equilibrium potential or chloride conductance of the basal membrane mediates the delayed basal response. PMID- 1915679 TI - Stimulation of rod outer segment phagocytosis by serum occurs only at the RPE apical surface. AB - The phagocytosis of isolated rod outer segments by cultured rat retinal pigment epithelium (RPE) previously has been shown to be stimulated by serum in the culture medium. In vivo, serum is normally in contact with the basolateral surface of the RPE. Components of serum have also been detected in the interphotoreceptor matrix, raising the possibility that these components may be in contact with the apical RPE surface. However, with conventional culture techniques it is not clear whether the stimulation of phagocytosis by serum occurs at the basolateral or apical surface. To resolve this uncertainty, phagocytosis was studied using RPE cultured on microporous filters, permitting control of which RPE surfaces are in contact with serum. Serum was found to have no influence on phagocytosis when present at the RPE basolateral surface, regardless of the serum concentration (2 or 20%). In contrast, phagocytosis was elevated three- to fivefold when 2% serum was present at the apical RPE surface, irrespective of the presence of serum at the basolateral surface. It is concluded that serum stimulates the phagocytosis of ROS only when the serum is present at the RPE apical surface. PMID- 1915680 TI - Age-related changes in local water and protein content of human eye lenses measured by Raman microspectroscopy. AB - The Raman microspectroscopic method was used to determine the local water and protein content in human lenses. In 18 lenses of varying age position-defined water/protein content measurements were carried out along the visual and the equatorial axis. A main characteristic of the human lens is its constant and relatively low protein content. In addition this constant nuclear value is reached within a short distance from the capsular surface. For statistical analysis of age-related changes the data points in individual lenses were piecewise linearized. (1) The mean nuclear water content was calculated from the data points in the inner 80% of the visual axis. (2) The steep drop in water content was linearized using a least-squares linear regression approach. The distance between lenticular surface and the intersection of the regression line with the line representing the nuclear mean was denominated as surface layer width. It proved that: (i) the mean nuclear water content significantly increased with age, (ii) the width of the surface layer was age independent in the anterior and posterior poles of the visual axis, and (iii) in the equatorial axis the surface layer width significantly decreased with age. Seven human lenses with small opaque spots were also investigated. The opaque spots proved to have a normal-for-site water content and some of them were flanked at their capsular side by a zone with a high-for-site water content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915681 TI - Development of the rabbit retina. IV. Tissue tensility and elasticity in dependence on topographic specializations. AB - A method is introduced for the quantification of specific compliance and the elasticity of small pieces of living retinal tissue. These pieces are fixed at their margins by means of tissue glue, and loaded with a small iron spherule the bending force of which can be gradually enhanced by the action of an electromagnet. Retinal bending caused by such calibrated forces is measured by a horizontal light microscope, and used for estimations of specific compliance and elasticity of the tissue. Three different particular regions of the rabbit retina -periphery, visual streak, and (prospective) medullary rays--were tested at several post-natal developmental stages. From very early stages on (day 2 p.p.) up to adulthood the peripheral retina was found to be significantly more tensile than the two other central regions. This can be shown to depend greatly on the thickness of the tissue which is lower in the retinal periphery. During early post-natal development, all retinal regions except the (prospective) medullary rays become thinner. The tensility of the tissue increases, with the exception of the medullary rays which reduce their compliance strongly. In the adult retina, however, the tensility of all retinal regions is reduced as compared with the neonatal tissue. This seems to be caused by a constant gradual increase of the elasticity of the retina during development which, in turn, may be caused by several developmental parameters, e.g. the formation of synapses, the outgrowth of glial side branches ensheathing neighbouring neuronal cells, or a reduction in extracellular clefts. It is proposed that these differences in tensility between different retinal regions, may be the cause for differential retinal expansion driven by the intraocular pressure. Thus, simple mechanical features of the tissue may contribute to the formation of important topographic specializations of the retina, e.g. the visual streak as the site of highest visual acuity. PMID- 1915682 TI - The glycation-associated crosslinking of lens proteins by ascorbic acid is not mediated by oxygen free radicals. AB - The reaction by which ascorbic acid (ASA) causes the glycation and crosslinking of lens proteins displays a rigid requirement for the presence of oxygen, and is inhibited by the presence of glutathione. Oxygen is required to oxidize ASA to dehydroascorbic acid (DHA) and other products which are the active glycating species. No evidence could be found to support a role for oxidative protein crosslinking by a free radical mechanism. Crosslinking was not inhibited by blocking protein sulfhydryl groups with iodoacetamide, nor were the protein crosslinks dissociated by boiling with 2% mercaptoethanol prior to SDS-PAGE. The addition of a variety of oxygen free radical quenchers had no effect on the extent of protein crosslinking. In fact, the removal of oxygen from the reaction mixture had no effect on either protein glycation, protein crosslinking or the modification of lysine residues, provided DHA was used as the glycating agent. All of these activities were inhibited, however, if ASA was the glycating agent. This confirms that oxygen is required only to convert ASA to DHA. PMID- 1915683 TI - Retinal microglia: a new cell in idiopathic proliferative vitreoretinopathy? AB - Despite numerous studies of the role of mononuclear phagocytes in proliferative vitreoretinopathy, the origin of these cells has remained obscure. Notably, retinal microglial cells have consistently been neglected. Applying double label immunohistology with a set of new cell markers to 37 preretinal traction membranes, we have identified a distinct population of proliferating cells presumably of microglial origin. The identification of microglia relies on positive labels for LN-1, Ricinus communis agglutinin-1, vimentin, HLA-DR, and nucleoside diphosphatase, and negative labels for Leu-M1, Leu-M3, EBM-11, von Willebrand factor, CD22, cytokeratin, and glial fibrillary acidic protein. Microglia are much more prevalent in idiopathic than in traumatic proliferative vitreoretinopathy and insignificant in proliferative diabetic retinopathy. HLA-DR expression was not restricted to pigment epithelium as previously reported but also observed in microglia, macrophages, endothelial and glial cells. The detection of retinal microglial cell proliferation suggests a pathogenetic role of these cells and questions current concepts of the cellular biology of proliferative vitreoretinopathy. PMID- 1915684 TI - Identification of bovine corneal protein 54 (BCP 54) as an aldehyde dehydrogenase. PMID- 1915685 TI - NASA plans and opportunities. PMID- 1915686 TI - On understanding the biology of aging: studies in space. PMID- 1915687 TI - Posture and the circulation: the age effect. AB - The primary instigator of circulatory response to the upright posture is the rapid displacement of about 10% of blood volume from the thorax to the lower body. The resultant hemodynamic deficit induces postural intolerance, especially orthostatic hypotension, in elderly over 70 years of age and in some young subjects after exposure to weightlessness. In this review, our objectives have been: 1) to describe in the normal subject the hemodynamic consequences of the headup posture, as well as lower body negative pressure, the compensatory responses intended to cope with these stresses, and their mechanisms; 2) to outline the effect of age on the circulatory responses to these stresses; and (3) to analyze and compare the tests currently used to assess circulatory tolerance. Our ability to design effective countermeasures to orthostatic circulatory intolerance is severely handicapped by our inadequate knowledge of the basic hemodynamic events incident to normal and abnormal orthostatic tolerance. We believe that better understanding and standardization of the postural tests, better experimental design to include greater emphasis on inter and intra individual variability, and wider application of currently available noninvasive circulatory techniques would greatly improve the prospects for success in this research area. PMID- 1915688 TI - Cardiovascular physiology in space flight. AB - The effects of space flight on the cardiovascular system have been studied since the first manned flights. In several instances, the results from these investigations have directly contradicted the predictions based on established models. Results suggest associations between space flight's effects on other organ systems and those on the cardiovascular system. Such findings provide new insights into normal human physiology. They must also be considered when planning for the safety and efficiency of space flight crewmembers. PMID- 1915689 TI - Age-related bone changes. AB - Bone changes occur during normal aging in both men and women. Changes are both quantitative and qualitative in nature, and include: 1) alterations in the dynamics of bone cell populations, resulting in uncoupling of the normal process of bone resorption and formation; 2) changes in bone architecture (e.g., rearrangement of trabecular struts) and cross-sectional geometry (characterized by subperiosteal expansion and enlargement of the medullary cavity); 3) accumulation of microfractures; 4) localized disparity in the concentration of deposited minerals, with hypomineralization in some areas and hypermineralization in others; 5) changes in the crystalline properties of mineral deposits; and 6) changes in the protein content of matrix material. In addition, there are age related changes in the status of calcium and phosphate regulating hormones: parathyroid hormone increases, and production of the most active metabolites of vitamin D3 decreases. These hormonal changes undoubtedly affect the maintenance of normal bone homeostasis. Other important factors which can profoundly influence bone status in the elderly are decreased physical activity and dietary inadequacies. Bone tissue is particularly responsive to mechanical loading, and the magnitude of bone mass loss as a consequence of decreased physical activity may not be fully appreciated. Interactions of the above mentioned changes are not completely understood, and the degree to which these changes have been documented in humans varies considerably. Clearly, however, the overall net result is the occurrence of age-related loss of bone tissue and bone strength. This process is accelerated after menopause in women, resulting in the clinical condition commonly known as osteoporosis. In addition to loss of bone mass (usually reported as a decrease in bone mineral content), osteoporosis is accompanied by bone pain, spinal deformity, loss of height, and fractures. PMID- 1915690 TI - Can the adult skeleton recover lost bone? AB - The loss of bone mineral with aging and subsequent development of osteoporosis is a common problem in elderly women, and as life expectancy increases, in elderly men as well. Space flight also causes bone loss and could be a limiting factor for long duration missions, such as, a Mars expedition or extended occupation of a space station. Before effective countermeasures can be devised, a thorough knowledge of the extent, location, and rate of bone loss during weightlessness is needed from actual space flight data or ground-based disuse models. In addition, the rate and extent that these losses are reversed after return from space flight are of primary importance. Although the mechanisms are not likely to be the same in aging and space flight, there are common elements. For example, strategies developed to prevent disuse bone loss or to enhance the rate of recovery following space flight might have direct applicability to clinical medicine. For various reasons, little attention has been given to recovery of bone mass following space flight. As a prelude to the design of strategies to enhance recovery of bone, this paper reviews published literature related to bone recovery in the adult. We conclude that recovery can be expected, but the rate and extent will be individual and bone site dependent. The development of strategies to encourage or enhance bone formation following space flight may be as important as implementing countermeasures during flight. PMID- 1915691 TI - The mechanical control system of bone in weightless spaceflight and in aging. AB - Bone loss is notable in elderly persons and in astronauts returning from spaceflight, however, the bone changes in these radically different patient populations appear morphologically similar. Bone structure depends upon several independent basic processes: growth, modeling, and remodeling. Each process follows a stereotyped sequence of steps. Alteration of any step may yield a similar bone loss, although from an entirely different mechanism. Mechanical forces appear to coordinate the fundamental bone shaping processes by a negative feedback control system. Determining how mechanical signals control the mass, architecture, and strength of bone may establish the limits by which exercise can prevent osteoporosis in the elderly and in astronauts despite obvious differences in etiology. PMID- 1915692 TI - Research on sleep, circadian rhythms and aging: applications to manned spaceflight. AB - Disorders of sleep and circadian rhythmicity are characteristic of both advancing age and manned spaceflight. Sleep fragmentation, reduced nocturnal sleep tendency and sleep efficiency, reduced daytime alertness, and increased daytime napping are common to both of these conditions. Recent research on the pathophysiology and treatment of disrupted sleep in older people has led to a better understanding of how the human circadian pacemaker regulates the timing of the daily sleep-wake cycle and how it responds to the periodic changes in the light dark cycle to which we are ordinarily exposed. These findings have led to new treatments for some of the sleep disorders common to older individuals, using carefully timed exposure to bright light and darkness to manipulate the phase and/or amplitude of the circadian timing system. These insights and treatment approaches have direct applications in the design of countermeasures allowing astronauts to overcome some of the challenges which manned spaceflight poses for the human circadian timing system. We have conducted an operational feasibility study on the use of scheduled exposure to bright light and darkness prior to launch in order to facilitate adaptation of the circadian system of a NASA space shuttle crew to the altered sleep-wake schedule required for their mission. The results of this study illustrate how an understanding of the properties of the human circadian timing system and the consequences of circadian disruption can be applied to manned spaceflight. PMID- 1915693 TI - Sleep and circadian rhythms. AB - The human biological clock or "circadian system" serves the function of preparing the body and mind for restful sleep at some times of day and active wakefulness at others. The observed circadian rhythms result from three interacting processes: endogenous rhythm generation mechanisms, entrainment mechanisms to keep these rhythms "on track," and exogenous masking processes stemming from changes in environment and behavior. In both advanced age and extraterrestrial travel these processes, particularly the latter two, can be dramatically effected with a consequent disruption in sleep and daytime functioning. We are currently studying the age-related effects on these processes in healthy 80 year olds using two different protocols. The first involved 36 h of constant wakeful bedrest which "unmasked" the endogenous component of circadian rhythms in various physiological and psychological functions. This experiment revealed little difference between nine old men and four young men in the endogenous body temperature rhythm, but revealed quite marked differences between the age groups in subjective activation and objective performance rhythms. A similar pattern occurred in the second experiment, which was a phase shift study comparing five old women with eight middle-aged men in their response to an acute 6 h phase advance in routine. Despite rather short-lived age-related differences in circadian rhythms, there were dramatic differences between the age groups in measures of sleep, mood, activation, and performance efficiency lasting for a week or more after the phase shift. PMID- 1915694 TI - Altered cell function in microgravity. AB - Physiological changes in humans during spaceflight upon return to earth have been attributed to systemic adaptation, response to stress, and lack of normal exercise. Studies from the Skylab, SL-3, and D-1 missions have demonstrated that significant physiological alterations are seen in single cell prokaryotes and eukaryotes, as well as in animal tissues. Basic cellular functions such as electrolyte concentration, cell growth rate, glucose utilization, bone formation, response to growth stimulation, and exocytosis are modified in microgravity. Many of the physiological changes seen in humans, vertebrate and simple organisms in spaceflight may originate from dysfunction of basic biological mechanisms caused by microgravity. Aging humans share many of the symptoms seen in astronauts during spaceflight. These include reduced cardiac function, loss of bone and reduced immune response and orthostatic hypotension. It is possible that some of physiological adaptations seen in aging may share common physiological basis with those changes seen in spaceflight. Since microgravity affects prokaryotic and eukaryotic cell function at a subcellular and molecular level, space offers us an opportunity to learn more about basic biological mechanisms which are essential to life. PMID- 1915695 TI - The pituitary: aging and spaceflown rats. AB - Decrements in growth hormone (GH) release we observed in two spaceflight experiments and four tail-suspended rat studies mimic age-associated changes in the mammalian pituitary GH system seen by Meites and others. The spaceflight data suggest that formation of high molecular weight bioactive disulfide-linked aggregates of the 20 and 22K monomeric GH forms may be reduced in microgravity, thereby, reducing target tissue activity. Correlative studies to confirm spaceflight as a model for pituitary GH system aging should include: 1) investigation of mechanisms of intracellular hormone packaging, 2) consequences to biological activity of the hormone molecule, and 3) study of intracellular microtubule dynamics. PMID- 1915696 TI - Heterogeneity of changes in lymphoproliferative ability with increasing age. AB - Although mean mitogen-induced lymphoproliferation decreases with increased age, the response of individual subjects demonstrates great heterogeneity. Results of this study clearly illustrate that individual variation is apparent not only in the level of proliferation, but also in the amount of interleukin-2 (IL-2) detectable after mitogen stimulation. Further, addition of exogenous IL-2 significantly increases proliferation in only about one third of elderly subjects. Data from inbred strains of rats housed under identical environmental conditions indicate that although genetic factors greatly influence both the level of proliferation and the rate of decline with age, variation occurs even within one inbred strain of rat. PMID- 1915697 TI - Cellular immunosenescence: an overview. AB - Recent studies on space flights suggest that certain T cell immunologic activities are vulnerable to microgravitation. It would be desirable to know the extent to which these changes can be prevented or reversed. Since the changes observed are analogous to the effects of aging on immunity, a brief overview is presented of our current knowledge of age-related changes in immune cells and of the various interventional methods which have been used successfully in preventing the decline with age and in elevating the levels of immune functions of old individuals. PMID- 1915698 TI - Immune response during space flight. AB - The health status of an astronaut prior to and following space flight has been a prime concern of NASA throughout the Apollo series of lunar landings, Skylab, Apollo-Soyuz Test Projects (ASTP), and the new Spacelab-Shuttle missions. Both humoral and cellular immunity has been studied using classical clinical procedures. Serum proteins show fluctuations that can be explained with adaptation to flight. Conversely, cellular immune responses of lymphocytes appear to be depressed in both in vivo as well as in vitro. If this depression in vivo and in vitro is a result of the same cause, then man's adaptation to outer space living will present interesting challenges in the future. Since the cause may be due to reduced gravity, perhaps the designs of the experiments for space flight will offer insights at the cellular levels that will facilitate development of mechanisms for adaptation. Further, if the aging process is viewed as an adaptational concept or model and not as a disease process then perhaps space flight could very easily interact to supply some information on our biological time clocks. PMID- 1915699 TI - Caenorhabditis elegans: a model system for space biology studies. AB - The utility of the nematode Caenorhabditis elegans in studies spanning aspects of development, aging, and radiobiology is reviewed. These topics are interrelated via cellular and DNA repair processes especially in the context of oxidative stress and free-radical metabolism. The relevance of these research topics to problems in space biology is discussed and properties of the space environment are outlined. Exposure to the space-flight environment can induce rapid changes in living systems that are similar to changes occurring during aging; manipulation of these environmental parameters may represent an experimental strategy for studies of development and senscence. The current and future opportunities for such space-flight experimentation are presented. PMID- 1915700 TI - Differential effect of adenosine on DNA synthesis in lymphoid and myeloid cell lines. AB - In this report, the effects of adenosine on the promyelocytic cell line HL-60 and on T-lymphocytic clones are compared. According to previous reports, adenosine induces a dose-dependent inhibition of DNA synthesis in T-lymphocytes. Conversely, adenosine dose-dependently enhances DNA synthesis in HL-60 cells, as documented with [3H]thymidine uptake studies and flow cytometric cell-cycle analysis. Unlike its effect on lymphocytes, the adenosine effect on HL-60 cells does not seem to be mediated by receptor binding, but it appears to be correlated with an intracellular mechanism following active uptake. Despite the different effects exerted by adenosine on lymphocytes and myeloid cells, a purinergic pathway appears to be more generally involved in the regulation of some phases of cell growth. PMID- 1915701 TI - Effect of doxorubicin exposure on cell-cycle kinetics of human leukemia cells studied by bivariate flow cytometric measurement of 5-iodo-2-deoxyuridine incorporation and DNA content. AB - Cell kinetics of two human leukemic cell lines, Molt-4 and K562, following a 2-h exposure to doxorubicin, were studied. DNA flow cytometry provided static information that for both cell lines a dose-dependent accumulation occurred at the G2 + M compartment that disappeared in time. Kinetic information was provided by time-monitoring cells labeled with 5-iodo-2-deoxyuridine (IdUrd) by two parameter flow cytometry, analyzing the IdUrd label and the DNA content. The cell cycle time (Tc) of exponentially growing Molt-4 cells was determined to be 20 h. Twenty-four hours after a 2-h exposure to 0.25 micrograms/ml doxorubicin, the Tc had increased to 23 h; following exposure to 1.0 micrograms/ml, it increased to 33 h. Cell kinetics of K562 cells following doxorubicin exposure were monitored in time up to 4 days. The average Tc of exponentially growing K562 cells was determined to be 24.7 h. Twenty-four hours following 2-h exposure to 0.25 or 0.5 micrograms/ml doxorubicin, the Tc were determined to be 28 and 32 h, respectively. After an additional 2 days, the Tc were both determined to be 24 h. The dose-dependent, reversible cell-cycle delay that persisted at least 48 h should be taken into account as an additional mode for decrease of a (tumor) cell population doubling time after exposure to doxorubicin. PMID- 1915702 TI - The role of monocyte-derived hemopoietic growth factors in the regulation of myeloproliferation in juvenile chronic myelogenous leukemia. AB - Juvenile chronic myelogenous leukemia (JCML) is a rare pediatric malignancy characterized by marked hepatosplenomegaly, leukocytosis with prominent monocytosis, elevated fetal hemoglobin, no Philadelphia chromosome, and generally a poor prognosis. In vitro, JCML peripheral blood granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM) demonstrate the unique characteristic of "spontaneous" proliferation at very low cell densities in the absence of exogenous growth factors. The "spontaneous" CFU-GM proliferation can be abolished by prior adherent cell (monocyte) depletion, suggesting a paracrine mode of cellular proliferation. Although previous studies using a [3H]thymidine ([3H]TdR) incorporation assay suggested an important role for granulocyte-macrophage colony-stimulating factor (GM-CSF) in JCML, many non growth factor-related reasons for [3H]TdR incorporation and the relatively low level of inhibition of [3H]TdR uptake left those conclusions open to question. Therefore, we performed clonal CFU-GM assays, which more specifically reflect cytokine effects on CFU-GM, using JCML peripheral blood mononuclear cells (PBMNC) and neutralizing antibodies against GM-CSF, granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating (M-CSF), interleukin 3 (IL-3), interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), interleukin 4 (IL-4), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF alpha), and interferon gamma (IFN gamma). Cultures containing anti-GM-CSF alone inhibited "spontaneous" JCML CFU-GM by 87% +/- 9% (mean +/- standard error of the mean [SEM]). No other anti-cytokine antibody produced a significant inhibition of CFU-GM growth. Various combinations of antibodies, excluding anti-GM-CSF, failed to demonstrate any synergistic inhibitory effects upon CFU-GM. Because this apparent paracrine cellular stimulation could be due to excessive cytokine production, by monocytes or other accessory cells, we examined cytokine levels in conditioned media from various JCML cell populations using enzyme-linked immunosorbent assays (ELISAs). Monocytes from only a minority of JCML patients produced higher than normal quantities of GM-CSF, G-CSF, IL-1 beta, IL-6, and/or TNF alpha, but no obvious pattern could be discerned. Further, only 7 of 15 JCML monocyte-conditioned media (MCM) had elevated GM-CSF, and 6 of 15 JCML patients had normal levels of all nine cytokines tested. The monocyte depletion experiments and the inhibition experiments with anti-cytokine antibodies taken together demonstrate clearly that the "spontaneous" growth of JCML CFU-GM in vitro critically depends on at least one monocyte-derived growth factor, GM-CSF.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915703 TI - Growth inhibition and differentiation in HL-60 leukemia cells induced by 1,25 dihydroxyvitamin D3 and tumor necrosis factor alpha. AB - Various concentrations of 1,25-dihydroxyvitamin D3 (vit D3; 10(-9)-10(-7) M) and recombinant human tumor necrosis factor alpha (rTNF-alpha; 60-960 U/ml) were used to induce growth inhibition and differentiation of the human promyelocytic leukemia cell line HL-60 based on growth kinetics, colony formation, morphological analysis, nonspecific esterase (NSE) activity, surface antigen expression, and cytokine release. Both vit D3 (10(-8)-10(-7) M) and rTNF-alpha (60-960 U/ml) were antiproliferative against the HL-60 cells, and a cooperative effect was noted when the two inducers were used in combination. After 5 days of incubation, vit D3 induced the HL-60 cells to differentiate into monocytes/macrophages, resulting in the formation of 3.0% +/- 0.4%, 18% +/- 2.0%, and 43% +/- 3.8% of morphologically mature cells at 10(-9), 10(-8), and 10(-7) M, respectively. The induced cells were NSE positive and expressed monocyte associated antigens (EBM11, CD11b, and HLA-DR). Conversely, rTNF-alpha (60-960 U/ml) was unable to trigger the HL-60 cells to differentiate. However, rTNF-alpha could apparently increase the proportion of the morphologically mature and NSE /antigen-positive cells when used in combination with vit D3 (10(-9)-10(-8) M). Following differentiation induction, HL-60 cells from vit D3-treated HL-60 cultures acquired the ability to secrete certain monokines, including interleukin 1 beta (IL-1 beta), prostaglandin E2 (PGE2), and granulocyte-macrophage colony stimulating factor (GM-CSF), and adding rTNF-alpha in addition to vit D3 invariably increased the production of IL-1 beta and PGE2. PMID- 1915704 TI - The effects of interleukin 6 and interleukin 3 on early hematopoietic events in long-term cultures of human marrow. AB - Interleukin (IL)-6 and IL-3, both alone and in combination, stimulate hematopoietic cells in short-term in vitro assays and in vivo. To study their ability to influence hematopoiesis in a system that mimics many features of the marrow microenvironment, long-term cultures (LTC) were produced by co-cultivating normal human marrow cells on feeder layers of murine marrow-derived stromal cells (M2-10B4 cells) genetically engineered to produce human IL-6 and/or IL-3. Feeders stably producing 20 ng/ml IL-6 slightly increased the output of clonogenic progenitors in these LTC but did not change the production of mature (total nonadherent) cells as compared to control cultures. Feeders producing 50 ng/ml IL 3 increased both clonogenic progenitor output (approximately threefold) and the output of mature cells (six-fold) as compared to controls. Feeders producing both factors also increased the output of both progenitors and mature cells. At the time of the weekly half-medium change when primitive clonogenic progenitors in the adherent layer are quiescent, such progenitors were actively cycling in all cultures with factor-producing feeders, as shown by [3H]thymidine suicide assays. Similarly, three sequential daily additions of 20 ng/ml of IL-6 also stimulated the quiescent progenitors to enter S-phase 2 days later, although single doses of recombinant IL-6 as high as 100 ng/ml failed to do so. The combined presence of IL-6- and IL-3-producing feeders, but neither alone, was also able to enhance more than twofold the maintenance and early differentiation of cells capable of generating clonogenic cells for at least a further 5 weeks in secondary LTC. Thus, the provision of a continuous source of IL-6 or IL-3 to primitive hematopoietic cells even in the LTC system can enhance late events in the hierarchy of hematopoietic cell differentiation, but a combination of the two factors is required to stimulate early multipotent progenitors. PMID- 1915705 TI - Correction by CSF-1 of defects in the osteopetrotic op/op mouse suggests local, developmental, and humoral requirements for this growth factor. AB - Mice that are mutant at the op locus have a severe deficiency of mononuclear phagocytes due to an inactivating mutation in the CSF-1 (macrophage colony stimulating factor, M-CSF) gene. op/op mice are toothless, possessing skeletal abnormalities, a low body weight, and compromised fertility; they are osteopetrotic due to a deficiency of osteoclasts. The congenital osteopetrosis, toothless phenotype, osteoclast deficit, and the defects in splenic and femoral macrophages were corrected by routes of administration of human recombinant CSF-1 that maintained normal circulating CSF-1 concentrations. Early restoration of circulating CSF-1 was required for rescue of the toothless phenotype, but only partially restored body weight. In contrast, the deficiencies of pleural and peritoneal cavity macrophages and the reduced female fertility were not corrected by restoration of circulating CSF-1. These results suggest that although circulating CSF-1 is required for osteoclast and macrophage production, local synthesis and action of the growth factor are important for certain target cell populations. PMID- 1915706 TI - Bioavailability of iron. PMID- 1915707 TI - Cholinergic modulation of optokinetic and vestibulo-ocular responses: a study with microinjections in the flocculus of the rabbit. AB - In spite of a large body of histochemical evidence for a cholinergic system in the cerebellum, particularly in lobules IX and X, the physiological role of such a system has remained obscure. In view of the important role of these same lobules in the control of the vestibulo-ocular (VOR) and optokinetic (OKR) responses, we tested the effect of microinjections of cholinergic (ant)agonists in the flocculus of the rabbit on these reflexes. Very marked effects were found. Bilateral floccular injection of the aspecific cholinergic agonist carbachol raised the gain of the OKR by about 0.46 above the baseline values, while the gain of the VOR in darkness was raised by about 0.14. These effects were statistically significant and persisted for several hours. Similar, but smaller effects were obtained after injection of eserine, an inhibitor of acetylcholinesterase. Thus, the effects could be produced by increasing the naturally present amount of acetylcholine. Microinjections of the nicotinic blocker mecamylamine reduced the gain of the VOR and OKR, although these effects did not reach statistical significance. The muscarinic blocker atropine significantly reduced the gain of the OKR, but not of the VOR. The present results argue strongly for an important physiological role of the cholinergic system in the cerebellum. Specifically, acetylcholine appears to be involved in the modulation of oculomotor reflexes through the flocculus. PMID- 1915708 TI - Responses to reward in monkey dorsal and ventral striatum. AB - The sources of input and the behavioral effects of lesions and drug administration suggest that the striatum participates in motivational processes. We investigated the activity of single striatal neurons of monkeys in response to reward delivered for performing in a go-nogo task. A drop of liquid was given each time the animal correctly executed or withheld an arm movement in reaction to a visual stimulus. Of 1593 neurons, 115 showed increased activity in response to delivery of liquid reward in both go and nogo trials. Responding neurons were predominantly located in dorsal and ventromedial parts of anterior putamen, in dorsal and ventral caudate, and in nucleus accumbens. They were twice as frequent in ventral as compared to dorsal striatal areas. Responses occurred at a median latency of 337 ms and lasted for 525 ms, with insignificant differences between dorsal and ventral striatum. Reward responses differed from activity recorded in the face area of posterior putamen which varied synchronously with individual mouth movements. Responses were directly related to delivery of primary liquid reward and not to auditory stimuli associated with it. Most of them also occurred when reward was delivered outside of the task. These results demonstrate that neurons of dorsal and particularly ventral striatum are involved in processing information concerning the attribution of primary reward. PMID- 1915709 TI - Generator study of brainstem auditory evoked potentials by a radiofrequency lesion method in rats. AB - The generators of brainstem auditory evoked potentials (BAEPs) in rats were investigated experimentally. Discrete lesions of the brainstem auditory pathway were made unilaterally using a stereotaxic radiofrequency coagulation method, and the BAEPs were recorded before and after the lesions to observe the alterations. The waves of the BAEPs were affected by the lesions as follows: (1) all of the BAEP waves were attenuated or eliminated by a lesion of the auditory nerve; (2) wave II was abolished or attenuated in amplitude following a lesion of the cochlear nucleus; (3) marked reduction or abolition of wave III occurred with some effect on waves IV and V following lesions of the superior olivary complex; (4) the following trough in the wave III was significantly attenuated by lesions of the lateral lemniscus that were associated with inconsistent changes in waves IV and V; (5) no waves were affected significantly by a lesion of the inferior colliculus. The method of radiofrequency lesion using stereotaxic localization proved to be a simpler and more rapid procedure for determining the generators of BAEPs in animals than other surgical lesion methods. PMID- 1915710 TI - Neonatal hyperthyroidism disrupts hippocampal LTP and spatial learning. AB - Excess thyroid hormone at an early stage of development produces marked neurochemical and morphological alterations in the rat hippocampal formation. In order to better understand the functional significance of these changes, we tested adult rats treated neonatally with triiodothyronine (T3), and their control litter mates, in a spatial learning task and for the induction of long term potentiation (LTP) in the dentate gyrus (DG) of the hippocampal formation. The T3-treated rats were significantly impaired in their performance on the spatial task in comparison to their matched controls. Similarly, the efficacy of LTP induction was significantly attenuated in the T3-treated animals. Further, a significant correlation was obtained between LTP induction and performance on the spatial learning task. Thus, a brief neonatal excess of thyroid hormone produces impairments in spatial learning along with decreases in LTP, long held as a model of learning and memory. This relationship provides a unique opportunity to study associations between behavioral, physiological, pharmacological and morphological processes intimately associated with the hippocampal formation. PMID- 1915711 TI - Sensitivity of external cuneate neurons to neck rotation in three-dimensional space. AB - A functionally meaningful vestibular-neck interaction, such as it has been demonstrated for postural reflexes and self-motion perception, requires the spatial and temporal response characteristics of vestibular and neck signals to be similar. We investigated the spatial coding in neurons of the external cuneate nucleus (ECN) with natural neck and vestibular stimulations, and compared them to that of neurons in the descending and medial vestibular nuclei (DVN and MVN, respectively) obtained with vestibular stimulation. Neurons were recorded extracellularly in chronically prepared cats held under light barbiturate anesthesia. Neck stimulation was performed by sinusoidally rotating the animals' trunk relative to the earth-fixed head in six different vertical planes and in the horizontal plane. Vestibular stimulation was elicited by whole-body rotations in the corresponding planes. During neck stimulation in the vertical planes, most ECN neurons showed an approximately sinusoidal discharge modulation about resting rate, which became maximal during rotation in a specific plane. Off this plane, the response declined along a cosine function and reached zero in the orthogonal plane. The majority of these ECN neurons also responded to horizontal neck rotation; the resulting "optimal" direction of rotation in three-dimensional space varied considerably among the neurons. Yet, there was a certain preference; the majority of these ECN neurons fired maximally if trunk rotation in the yaw plane stretched the neck on the ipsilateral side, if roll brought the contralateral shoulder closer to the head, and if pitch brought the back closer to the occiput. A minority of ECN neurons showed more complex response patterns which could not be described by a single, optimal direction. About one third of the neck-sensitive ECN neurons tested showed weak responses during whole body rotation, which might stem from a weak vestibular input to this nucleus. In the DVN and MVN, the optimal direction in three-dimensional space with vestibular stimulation typically had a cosine-like spatial tuning. The spatial distribution of these directions clearly differed from that of neck-sensitive neurons in the ECN. We therefore assume that a further processing of the two input signals takes place at later stages in the CNS (e.g., in the vestibulo-cerebellum) in order to yield a functionally useful vestibular-neck interaction. PMID- 1915713 TI - Transient increase of contraversive saccade parameters following kainic acid injection in the periparabigeminal area of guinea pig. AB - Anatomical and electrophysiological data have shown that, in the guinea pig as well as in the cat, the nucleus prepositus hypoglossi gives rise to a disynaptic ascending projection to the superior colliculus via the peri-parabigeminal area in the mesencephalon. The functional role of this indirect pathway in the generation of eye movements has been studied by pharmacologically interfering at the mesencephalic level and by examining the induced effects on two differently elicited saccades in the alert guinea pig. A small iontophoretic injection of kainic acid induces a transient increase of the spontaneous saccadic activity in the contraversive direction leading to a pseudo-nystagmus. Both the amplitude and the mean velocity of the contraversive saccades are greater than before the injection. A similar enhancement also affects the parameters of the contraversive saccades induced by trunk rotations. These results suggest that peri parabigeminal neurones exert an excitatory influence on their target cells in the ipsilateral superior colliculus which is responsible for contraversive rapid eye movements. PMID- 1915712 TI - Serotonin immunoreactive neurons are present in the superficial layers of the hamster's, but not the rat's, superior colliculus. AB - Immunocytochemistry for serotonin (5-HT) was carried out in both hamsters and rats in order to determine whether or not 5-HT-positive cells existed in the superior colliculus (SC) of either species. In both hamster and rat, the superficial and deep SC laminae contained dense networks of 5-HT-positive fibers. The rat's SC contained no 5-HT-positive neurons. In hamster, numerous 5-HT immunoreactive cells were visible throughout the depth of the stratum griseum superficiale (SGS). These neurons had a variety of morphological characteristics and included marginal cells, horizontal cells, and neurons with vertically oriented dendritic trees. No 5-HT-positive neurons were found in any other portion of the hamster's SC. 5-HT-positive SC cells were observed with antisera from two different sources and they were not seen in animals that were pretreated with reserpine. Pretreatment with fluoxetine (an inhibitor of 5-HT uptake) also resulted in a disappearance of 5-HT-positive neurons in the hamster's SC. This result indicated that "serotonergic" cells in the colliculus of this species are capable of taking up, but probably not synthesizing, this indoleamine. The dorsal and ventral lateral geniculate nuclei (LGNd and LGNv, respectively) both contain numerous 5-HT-positive fibers and both of these structures receive input from the SGS. Combination of retrograde tracing with fluorogold and immunocytochemistry indicated that 5-HT-accumulating SC neurons were not the source of these fibers. Unilateral ablation of the superficial SC laminae also failed to reduce 5-HT immunoreactivity in either the LGNd or LGNv. These results are consistent with the possibility that 5-HT-accumulating cells in the hamster's SC may be interneurons that take up this transmitter after it is released by afferents to this nucleus. PMID- 1915714 TI - Interocular mismatch in spatial frequency and directionality characteristics of striate cortical neurones. AB - Spatial-frequency dependence of directional tuning and directional bias was compared, for both eyes, in four previously established discrete classes of binocular feline striate cortical neurones. Two classes (respectively direction selective or bidirectional at optimal spatial frequency) were directionality invariant at all spatial frequencies. In the remaining two classes, both direction-biased at optimal spatial frequency, directional bias either altered or reversed with change in spatial frequency. In all four classes, the directional tuning of a majority of neurones sharpened at high spatial frequency through either eye, although the bandpass characteristics were sometimes dissimilar for the two eyes. All neurones were of the same type through either eye. Amongst the two classes of direction-biased neurones, the strength of bias was commonly different through the two eyes. Where reversal of bias occurred, that reversal took place at different spatial frequencies for each eye. Thus, the direction and orientation preferences of cortical neurones are fixed at optimal spatial frequency, but their envelope of tuning to a gamut of spatial frequencies is not. These differences are potentially related to binocular coding of visual perspective, including dynamic object rotation in visual space. PMID- 1915715 TI - Visual and vestibular signals in the lateral mesencephalic tegmental region of the cat. AB - Single unit recordings from two alert cats were used in an attempt to further elucidate the function of the lateral mesencephalic tegmental region (LTR), a part of the mesencephalon forming a link between the superior colliculus and the lower brain stem. A total of 155 units recorded from the LTR were tested with visual, vestibular and acoustic stimuli. Of these, 54 cells (36%) were characterized as either visually (n = 33) or vestibularly (n = 21) responsive and an additional 13 cells were driven by complex acoustic stimuli. Visually responsive cells typically were directionally selective with large, mainly contralateral receptive fields. Vestibularly responsive cells were modulated by stimulation of either the horizontal canals (yaw stimulation; n = 16) or of both pairs of vertical canals (pitch stimulation; n = 5). About half of the cells with activity modulated by rotation about the yaw axis increased discharge during ipsiversive (Type I), the other half during contraversive rotation (Type II). Of the 5 cells with activity modulated by pitch stimulation, 4 preferred the nose down and only 1 the nose-up direction. Although the discharge of units responsive to yaw stimulation was roughly in phase with head velocity (mean phase lag with respect to head velocity: 10.6 deg), none of the vestibular cells had activity correlated with eye position, eye velocity or movement of visual stimuli. Our observations suggest that the LTR might introduce visual and vestibular signals into the tecto- facial pathway which may be used to adjust the size of pinna movements with respect to the size of ongoing head- or body movements. PMID- 1915717 TI - Age differences in visual sensory integration. AB - Numerous authors have reported that elderly persons are more affected than young adults when submitted to reduced or conflicting sensory inputs conditions. These results, however, do not permit to evaluate whether the elderly suffer from a reduced peripheral sensibility or from a deficit in the central integrative mechanisms responsible for configuring the postural set. The present experiment evaluated the ability of elderly to reconfigure the postural set when submitted to successive reduced and augmented visual sensory conditions. Results showed that young and elderly subjects' sway dispersion increased when they were exposed to a reduced visual sensory condition (i.e., vision/no-vision transition). However, when exposed to augmented sensory condition (i.e., no-vision/vision transitions) young adult were able to adapt rapidly and reduced their sway dispersion whereas the elderly exhibited an increased sway dispersion. This inability to adapt to an augmented sensory condition suggest that elderly persons, in addition to a reduced peripheral sensibility, have a deficit with central integrative mechanisms responsible for reconfiguring the postural set. PMID- 1915718 TI - Compensatory eye movements in the presence of conflicting canal and otolith signals. AB - Orbital motion of the head with the face directed towards the axis of rotation is a stimulus to the otolith organs which is in the opposite rightwards-left-wards sense to the rotational stimulus to the semicircular canals. This can be experienced, for example, by a child held at arms length "en face' and swung from side to side. As one swings, say to the right, the child's head rotates to its right yet moves linearly to its left. Eye movement responses to a transient orbital movement were observed whilst subjects fixated earth-fixed targets. i) a "near target" placed between the head and the axis whose relative displacement is in the same direction as head rotation, and ii) a "far target" placed beyond the axis whose relative motion is in the opposite direction to head rotation. The motion stimuli evoked slow phase eye movements at 45 ms latency, always in the opposite direction to head rotation, thus compensating for the motion of the far target but in the wrong direction for fixating the near target. Theoretically, fixating the near target demands a predominance of the otolith ocular-reflex, which would give an eye movement in the correct direction. However, despite visual cues, it seems that if the canal and otolith-ocular reflexes are evoked in opposing directions, the otolith reflex fails to operate at a sensitivity sufficiently high to reverse the direction of the canal-reflex. PMID- 1915716 TI - Coordination of hand movements and saccades: evidence for a common and a separate pathway. AB - We studied the reaction times and initial directions of hand movements and saccades of human subjects who fixated and pointed as quickly as possible at eccentric targets which were presented unexpectedly. The targets were positioned on a horizontal bar which was placed in front of the subject. Different stimulus conditions were used in the experiments. Knowledge of the target position or the presence of an auditory co-stimulus slightly affected the reaction times of saccades in response to visual stimuli. Auditory co-stimuli reduced the reaction times considerably when the targets were presented after a delay of 200 ms after extinction of the central fixation point. Similar reductions were observed in the reaction times of the hand movements. However, these reductions were seen in hand responses to undelayed as well as delayed target presentations. The saccades were always made in the correct direction when the target was presented without delay. When the target was delayed about 50% of the saccades were made in the wrong direction. Even for undelayed targets the hand sometimes made mistakes. The number of mistakes increased to 35% when the target presentation was accompanied by the sound pulse. For delayed targets the proportion of wrong hand movements was about 50%. For such targets saccades and hand movements were practically always made in the same direction. If visual information is available, saccades and hand movements are generated independently of each other. However, if visual information is not present at the appropriate time and the target position has to be guessed, saccades and hand movements are generated on the basis of shared information.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915719 TI - Myelination of the rat retina by transplantation of oligodendrocytes into 4-day old hosts. AB - Oligodendrocyte transplantation into the retina enables us to investigate the early events in myelin formation in a new in vivo system. The axons of rat retinal ganglion cells are unmyelinated in the eye but should express a myelination initiation signal since they acquire myelin posterior to the globe. The lamina cribrosa may block the migration of oligodendrocytes from the optic nerve into the retina. Animals that lack a lamina cribosa such as the rabbit have myelinated retinas. We have bypassed the lamina cribrosa by using transplantation techniques and inserted freshly isolated syngeneic 3-week-old rat oligodendrocytes into the unmyelinated 4-day-old rat retina during the period of active optic nerve myelination. The animals are sacrificed at 1-week intervals for 8 weeks. The retinas are examined immunocytochemically for myelin with an antibody to myelin basic protein (MBP). MBP-positive cells are seen extending processes at 1 and 2 weeks. Three and four week retinas show the formation of thicker and longer myelin sheaths oriented along the same radial path as the retinal ganglion axons with maximal MBP staining intensity seen by 5 weeks. Transplanted retinas are negative when stained for P0, a Schwann cell antigen, ruling out Schwann cell myelination of our retinas. We have shown that rat cerebral oligodendrocytes survive, mature, and express a myelin-specific protein in the retinal environment in a pattern consistent with myelination of ganglion cell axons. Retinal transplantation provides a new in vivo model to study oligodendrocyte development and axonal-glial interactions, free from the difficulties inherent in culture systems. PMID- 1915720 TI - Monosialoganglioside GM1 reduces NMDA neurotoxicity in neonatal rat brain. AB - Monosialoganglioside GM1 prevents excitatory amino acid (EAA)-related neuronal death in cultured central nervous system (CNS) neurons and reduces the severity of acute brain damage in different experimental models of cerebral ischemia. Using a model of brain damage induced by intracerebroventricular administration of N-methyl-D-aspartate (NMDA) in neonate rats, we evaluated whether GM1 is capable of exerting antiexcitotoxic effects following its systemic administration in vivo. Newborn rats subjected to brain damage by NMDA and contemporaneously treated subcutaneously with GM1 showed significantly reduced (i) loss in hemispheric weight, (ii) loss in tissue choline acetyltransferase activity, and (iii) morphological damage in various brain areas. These results indicate that systemic GM1 treatment is efficacious in reducing EAA-related neuronal damage in vivo and suggest that such a phenomenon may underlie its capability to ameliorate neurological outcome following cerebral ischemia. PMID- 1915721 TI - Electrical properties of axons within probst bundles of acallosal mice and callosi that have reformed upon glial-coated polymer implants. AB - Lesioning of the developing cerebral midline and corpus callosum of mice results in the formation of bilateral masses of axons known as Probst's longitudinal bundles. These ectopic axons were examined using an in vitro brain slice technique, and they were found to be functional and to have electrical properties that were similar to those of the unlesioned corpus callosum at a comparable age. When a nitrocellulose bridge is properly oriented at the site of the callosal lesion in neonates, the implant will support the migration of glia which, in turn, promote the redirection of callosal axons across the midline. These axons were also analyzed by in vitro brain slice techniques, and they were found to be functional and to have electrical properties that were similar to the unlesioned corpus callosum with respect to conduction velocity and chronaxie but dissimilar with respect to charge threshold and rheobase current. PMID- 1915722 TI - Ultrastructural changes in the blood-brain barrier after nimodipine treatment and induced hypertension. AB - Fourty-four narcotized rats were split into two equal groups, one being treated with nimodipine and the other with a placebo. By use of norfenefrine the blood pressure was raised to values of 150 and 180 mm Hg within the limits of the autoregulation of brain perfusion and under continuous measurement. Fifteen minutes after application of the standard tracer, horseradish peroxidase, the animals were exsanguinated using a saline perfusion and then perfusion-fixed with Karnovsky's solution. After development of the peroxidase staining the brain sections were evaluated and then allocated to their respective groups. In brain tissues from the experimental group significantly more frequent perivascular accumulations of horseradish peroxidase reaction product were found (P less than 0.001). In electron micrographs it could be seen that the tight junctions were intact and that there was a neuroendothelial transport, with horseradish peroxidase-filled vesicles, in the endothelium, muscle cells, and brain parenchyma. These vesicles represent a medium of transport for all proteins of high molecular weight and can therefore result in brain edema. It is concluded that nimodipine damages the blood-brain barrier by disturbance of the autoregulation of the cerebral blood flow. PMID- 1915723 TI - Behavioral recovery following intrastriatal implantation of microencapsulated PC12 cells. AB - The motor deficits associated with Parkinson's disease may be ameliorated by intrastriatal placement of dopamine-secreting cells in a polymer capsule. Water soluble polyelectrolytes were utilized for membrane encapsulation of dopamine secreting PC12 cells. Membrane permeability studies revealed exclusion of radiolabeled 69,000 Da albumin, whereas 30,000 Da carbonic anhydrase was able to cross the membrane. No cytolytic activity was observed following incubation of the encapsulated PC12 cells with PC12 cell-directed antiserum and fresh complement. In vitro, dopamine release and the surface area of intact cells per microcapsule, reached a plateau at 4 weeks that was maintained for at least 12 weeks. Viable PC12 cells were observed in microcapsules implanted for 4 and 8 weeks in nonlesioned guinea pig striata. The behavioral effect of intrastriatal dopamine release from microencapsulated PC12 cells was evaluated in the 6 hydroxydopamine unilaterally lesioned rat model. From 1 to 4 weeks postimplantation a significant reduction in rotation behavior under apomorphine challenge was observed with PC12 cell-loaded microcapsules as compared to empty microcapsules. Tyrosine hydroxylase immunopositive PC12 cells were observed 4 weeks postimplantation in all animals exhibiting a reduction in turning behavior. Implantation of polymer-encapsulated cells may provide a means for long-term delivery of neurotransmitters and growth factors to the nervous system. PMID- 1915724 TI - Viral Kirsten ras infection differentiates PC12 cells and enhances their survival upon implantation into brain. AB - Neuronal cells from established cell lines can offer a well-characterized source of cells for transplantation to the brain that is an alternative to fetal neurons. The infection of members of the PC12 cell line with a retrovirus containing ras-oncogene leads to their neuronal differentiation without the need of nerve growth factor (NGF). We find that neoplastic, naive PC12 cells grafted to the striatum of normal adult rats cause the transient formation of large hemorrhagic cavities and do not survive. After differentiation by infection with Kirsten-ras murine sarcoma virus, and transplantation to the opposite striatum of the same brain, PC12 cells survive for at least 8 weeks and emit neurites. These neuron-like cells and their neurites retain tyrosine hydroxylase and choline acetyl transferase, as detected immunohistochemically. Thus, ras-primed PC12 cells may serve as a continuous source for both cholinergic and adrenergic transmitters, in vivo, without the need of exogenous nerve growth factor. PMID- 1915725 TI - Loss of intensity-induced inhibition in inferior colliculus neurons leads to audiogenic seizure susceptibility in behaving genetically epilepsy-prone rats. AB - The genetically epilepsy-prone rat (GEPR) exhibits elevated seizure sensitivity and audiogenic seizures (AGS). The inferior colliculus (IC) is the most critical brain region for AGS initiation. The present study evaluated IC neuronal firing and convulsive behavior simultaneously in freely moving GEPRs. High intensity acoustic stimulation produces neuronal firing reductions (intensity-induced inhibition) in about 50% of IC neurons in normal rats. However, in GEPR IC neurons, intensity-induced inhibition is significantly less effective than normal. Offset inhibition is also reduced in GEPR IC neurons, which leads to a greater than normal incidence of offset (afterdischarge) responses at high stimulus intensities. At AGS onset most IC neurons exhibit burst firing and reductions of acoustically evoked neuronal responses. Responsiveness to acoustic stimuli returns following AGS. This change in IC neuronal firing pattern suggests that the network that governs IC neuronal firing has temporarily changed from the auditory system to the network that mediates seizure propagation. GABA is strongly implicated in intensity-induced, binaural, and offset inhibition in IC neurons. The diminished efficacy of these forms of GABA-mediated acoustically evoked inhibition in the GEPR IC extends previous results, showing reduced effectiveness of exogenously applied GABA and benzodiazepine in GEPR IC neurons. This reduced effectiveness of GABA-mediated inhibition along with excess excitant amino acids in GEPR IC, previously reported, appear to be vital neurotransmitter mechanisms, subserving the exaggerated output of IC neurons at high acoustic intensities. This exaggerated IC firing may be instrumental in seizure initiation in this epilepsy model. PMID- 1915726 TI - In vitro models differentiating between direct and indirect effects of ischemia on astrocytes. AB - Mouse astrocytes in primary cultures were subjected to an in vitro model of ischemia (hypoxia combined with substrate deprivation, excess potassium, or elevated glutamate) and examined with the light (phase) and electron microscope. Three hours of hypoxia alone or in combination with the other insults had little effect upon the morphology of astrocytes but did cause disaggregation of polyribosomes. With reoxygenation, polyribosomes reformed and many mitochondria changed from the orthodox to the condensed configuration. Notably, there was little swelling. Excess (50 mM) potassium, added (as KCl) to a normal isotonic medium, also caused no swelling. However, when 50 mM potassium was substituted for a similar amount of sodium, marked astrocyte swelling did occur. A morphologically similar swelling was seen when glutamate (50 microM to 1 mM) was added to the culture medium, both with or without hypoxia with or without substrate deprivation. Potassium or glutamate-induced swelling was reversible with 1 h of recovery in normal medium. These results show that alterations in postischemic astrocytic morphology in vivo to a large extent can be reproduced in astrocytes in primary cultures. In addition, they suggest that postischemic astrocyte swelling is related to alterations in extracellular milieu, including accumulation of glutamate and/or alterations in the potassium/sodium ratios with increased potassium and decreased sodium. In contrast, morphologic alterations in polyribosomes and in mitochondria appear to be a direct response to ischemia itself. PMID- 1915727 TI - The influence of postmortem delay on evoked hippocampal field potentials in the in vitro slice preparation. AB - The influence of postmortem delay, and thus in situ anoxia/ischemia, on the recovery, viability, and maintenance of in vitro hippocampal slices was studied parametrically. Brains from rats were kept in situ for delays of 5, 30, 60, 90, 120, or 180 min before dissection and slicing of the tissue. Using standard in vitro conditions, Schaffer collateral and perforant path-evoked field potentials were recorded in the respective cell layers at 2, 4, and 8 h after beginning in vitro maintenance. With submaximal stimulus intensities the percentage of slices displaying at least a 1-mV population spike remained above 20% for all postmortem delays, and this measure of viability was indistinguishable (65%) across the delays of 5 and 30 min in both CA1 and fascia dentata (FD). The amplitudes of the EPSP and population spike and the population spike-to-EPSP ratio tended to decline with anoxic delay in both CA1 and FD; however, approximately half-maximal population spikes averaged greater than 3 mV, even for the longest postmortem delay of 3 h. These results indicate that the delay between death and preparation of in vitro hippocampal slices is less important for obtaining physiologically viable slices than previously believed. These data also imply that meaningful electrophysiological information about premortem brain conditions may be inferred from nervous system tissue which is not available immediately after death. PMID- 1915728 TI - Golgi, histochemical, and immunocytochemical analyses of the neurons of auditory related cortices of the rhesus monkey. AB - Morphological characteristics of the neurons of the auditory cortical areas of the rhesus monkey were investigated using Golgi and horseradish peroxidase methods. Neurons of the auditory cortices can be segregated into two categories, spinous and nonspinous, which can be further subclassified according to their dendritic arrays. The spinous neurons include pyramidal, "star pyramid," multipolar, and bipolar cells. As in other cortices, pyramidal cells are found in layers II-VI and appear to be the most numerous of all cortical neurons. The "star pyramids" have radially oriented dendrites with a less prominent apical shaft and are found mainly in the middle cortical layers. The spinous multipolar neurons are also found in the middle cortical layers and have their dendrites radially arrayed but have no apical dendrite. The spinous bipolar cells, found in the infragranular layers, occur most frequently in the lateral auditory association cortex. The nonspinous neurons include neurogliaform, multipolar, bitufted, and bipolar cells and are found in all cortical layers. The neurogliaform cells are the smallest of all neurons and have radially arrayed, recurving dendrites. The nonspinous multipolar cells also have radially arrayed dendrites but vary in size from being confined to one cortical layer to extending across four laminae. The bitufted neurons are subclassified into three groups: neurons whose primary dendrites arise radially from their somata, those whose dendrites arise from two poles of their somata, and those that have a single primary dendrite arising from one pole and multiple dendrites from another pole of their somata. The nonspinous bipolar cells also have several variants but usually have dendrites arising from two poles of the somata. The chemical characteristics of the auditory neurons were investigated using histochemical and immunocytochemical methods. Peptidergic neurons, i.e., cholecystokinin-, vasoactive intestinal polypeptide-, somatostatin-, and substance P-reactive neurons are found in the various subregions of the auditory cortices and are distributed differentially in the cortical laminae. These neurons are of the nonpyramidal type. Gamma aminobutyric acid-reactive neurons are also nonpyramidal cells and they are found in all cortical layers. Their numbers varied among the cortical laminae in the different auditory regions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915729 TI - GM1 ganglioside treatment reduces functional deficits associated with cortical focal ischemia. PMID- 1915730 TI - A novel assay for the in vivo study of Schwann cells. AB - An in vivo assay was developed for long-term analyses of Schwann cells at the single cell level. Schwann cells were isolated from sciatic nerves and labeled with the fluorescent gold label Fluoro-Gold. Cells were then transplanted into severed sciatic nerves of young adult rats. Gold-labeled Schwann cells, identified by double-labeling with S100 antibodies, were observed up to 10 mm away from the transplant site and after 90 and 120 days of survival in vivo. PMID- 1915731 TI - Decreased levels of [Met]enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide in parkinsonian adrenal medulla. AB - Adrenal medullary tissue was collected from parkinsonian patients at autopsy and at the time of autologous transplantation of the adrenal medulla to the caudate nucleus, and from nonparkinsonian patients at autopsy and during nephrectomy. Levels of the following neuropeptides were measured by radioimmunoassay in samples of the medullary tissue: neuropeptide Y (NPY), substance P (SP), [Met]enkephalin ([Met]ENK), vasoactive intestinal peptide (VIP), peptide YY, and bombesin-like immunoreactivity. Regression analysis was used to establish a relationship between patient age, time to organ harvest, and peptide levels in nonparkinsonian tissue. Levels of [Met]ENK, VIP, NPY, and SP were significantly lower in parkinsonian adrenal medullae than that predicted from the control group. These results suggest that the adrenal medulla of a parkinsonian patient is severely compromised, either by the disease process itself or by the antiparkinsonian medications used to treat the symptoms of the disease. PMID- 1915732 TI - Levodopa reduces the growth promoting effects of striatal extracts on rostral mesencephalic tegmentum cultures. AB - Rats with unilateral 6-hydroxydopamine lesions (6-OHDA) of the mesencephalon and vehicle controls (SHAM) were chronically treated with carbidopa (CD) or CD plus levodopa (CD/LD) for 18 days. Seventy-two hours following the last treatment, ipsilateral striata, contralateral striata, and cerebellums from each treatment group were homogenized separately and the supernatant extracts were incubated with rostral mesencephalic tegmentum cultures. As indices of growth-promoting activity (GPA), number of viable neurons and their process lengths were measured 40 h later. In all cultures exposed to striatal extracts, the 6-OHDA lesion was associated with greater GPA than the SHAM extracts. CD/LD consumption reduced this GPA in a dose-dependent fashion in both the lesioned and the SHAM animals. These data suggest that denervation of the striatum enhances the production of a striatally derived neurotrophic factor, the production of which is sensitive to levodopa. Chronic levodopa treatment in Parkinson's disease may therefore contribute to disease progression by reducing the compensating effects of this neurotrophic factor on remaining mesencephalic neurons. PMID- 1915733 TI - Hippocampal damage and kainic acid injection induce a rapid increase in mRNA for BDNF and NGF in the rat brain. AB - In situ hybridization and Northern blots were used to study expression of mRNAs for members of the nerve growth factor family in the rat brain following an excitatory stimulus. One hour after a unilateral needle insertion or saline injection into the dorsal hippocampus, the level of brain-derived neurotrophic factor (BDNF) mRNA increased markedly in granular neurons of the dentate gyrus and in the piriform cortex ipsilateral to the injection. The same treatment also increased the level of NGF mRNA in granular neurons of the ipsilateral dentate gyrus. The rapid increase in BDNF and NGF mRNA after a needle insertion or injection of saline was transient and preceded by an increase in c-fos mRNA in the same brain regions. In contrast to a needle insertion per se or a saline injection, 7 h after a unilateral injection of kainic acid into the dorsal hippocampus, the level of BDNF mRNA was dramatically increased in the ipsilateral hippocampus, as well as in the ipsilateral frontoparietal, piriform and perihinal cortex, the amygdaloid complex, claustrum, and ventromedial hypothalamus. A less pronounced increase was also seen in these brain areas on the contralateral side. Northern blots revealed that the level of BDNF mRNA increased 5- and 40-fold in the contra- and ipsilateral hippocampus, respectively, compared to sham-operated control animals. In contrast to BDNF and NGF, the level of hippocampus-derived neurotrophic factor/neurotrohin-3 (HDNF/NT-3) mRNA was not altered by either needle insertion or injection of saline or kainic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915734 TI - Differential effects on sensory nerve processes and behavioral alterations in the rat after treatment with antibodies to nerve growth factor. AB - Published work on the effects of antibodies to nerve growth factor (ANTI-NGF) treatment on rats has shown an increase in the number of unmyelinated central processes of dorsal root ganglia (DRG) neurons (31). This increase is interpreted to be sprouting of the central projections of the DRG neurons. To test for sprouting of the peripheral DRG projections, we quantitated the number of peripheral DRG processes in the peripheral nerves of ANTI-NGF-treated compared to untreated rats, following selective surgery to eliminate motor and sympathetic nerve fibers. We report the numbers of peripheral DRG processes in an NGF deprived environment decrease by 48% compared to untreated controls and the decrease is selective for the unmyelinated fiber population. Since the majority of the unmyelinated population is nociceptive, two nociceptive behavioral measures, one reflexive (tail flick) and one nonreflexive (paw or skin pinch), were performed and demonstrated decreased responses in the ANTI-NGF-treated compared to untreated and preimmune-treated rats. These data suggest a directional effect, primarily on the unmyelinated sensory population which results in altered nociceptive behavior, induced by the suppression of one endogenous factor, NGF. Furthermore, it is important to note that the centrally directed sensory processes project to a central nervous system environment and the peripherally directed processes are in a peripheral nervous system environment. Thus, a single molecule may have different effects on directional growth of a neuronal population that may be related to the interactions available in the substrate of the environment. PMID- 1915735 TI - Trajectory of redirected corticospinal axons after unilateral lesion of the sensorimotor cortex in neonatal rat; a phaseolus vulgaris-leucoagglutinin (PHA-L) tracing study. AB - The corticospinal neurons of the rat project almost exclusively to the contralateral spinal cord. Retrograde and anterograde tracing experiments showed that only about 2-4% of the corticospinal neurons of the sensorimotor cortex project to the ipsilateral spinal cord in the normal rat. The large majority of corticospinal axons (more than 90%) travel at spinal level at the base of the contralateral dorsal funiculus; in addition a few axons run in the contralateral lateral funiculus and at the base of the dorsal horn. The undecussated axons run in the ipsilateral dorsal (about 1-2%) and ventral (about 1-2%) funiculi. The rearrangement of the corticospinal projections was studied with various tracing methods in rats subjected to unilateral lesion of the sensorimotor cortex at Postnatal Day 2 to 4. Spinal injections of the tracer WGA-HRP that were restricted to the side opposite to the cortical lesion showed a significant increase of retrogradely labeled corticospinal neurons in the intact cortex as compared to the proportion of ipsilateral projections in control experiments. This was consistent with an increased density of anterogradely labeled corticospinal terminals in the spinal cord ipsilateral to an injection of WGA-HRP in the motor cortex opposite to neonatal lesion, in comparison to normal rats. The trajectory of these "aberrant" ipsilateral corticospinal projections resulting from the neonatal lesion of the opposite sensorimotor cortex was analyzed by means of the anterograde tracer phaseolus vulgaris-leucoagglutinin (PHA-L), injected in the motor cortex. These data indicated that decussated corticospinal axons recross at spinal levels, close to their terminal zone, where they appear to ramify and terminate in the spinal gray including the motoneurons. Such recrossing axons thus represent one new possible mechanism, among other previously reported ones, contributing to the increase of ipsilateral corticospinal projections in rats subjected to neonatal cortical lesion. PMID- 1915736 TI - The focally demyelinated rat fimbria: a new in vitro model for the study of acute demyelination in the central nervous system. AB - We have produced controlled local demyelination in Wistar rat fimbriae by injection of microliter quantities of the detergent lysophosphatidyl choline (LPC) stereotactically. Six to seven days later the hippocampus and fornix was dissected out en bloc and maintained in vitro for electrical evaluation of conduction through the damaged area. The tissue was then fixed for verification of the lesion by light and electron microscopy. All fimbriae showed a normal conducted action potential with a latency of 0.5 to 1.5 ms when the conduction distance was 4-5 mm. LPC-lesioned fimbriae also showed a later wave with a latency of 4-5 ms. This later wave had the same stimulus-response curve as the primary action potential, but was more sensitive to repeated stimulation. We interpret this wave as evidence of conduction into or through a demyelinated region. LPC-lesioned fimbriae also showed histological evidence of demyelination. This preparation provides an in vitro model for the study of acute local demyelination of central nervous system white matter, such as that induced by multiple sclerosis and other focally demyelinating diseases. PMID- 1915737 TI - Distribution and number of transferrin receptors in Parkinson's disease and in MPTP-treated mice. AB - Transferrin is a glycoprotein that functions primarily to deliver iron to the cell. Recent studies suggest that the transferrin receptor mediates the intracellular delivery and transport of iron bound to transferrin in the CNS. Iron-catalyzed free radical generation has been proposed as a possible cause of nigral cell death in Parkinson's disease. Our hypothesis is that abnormal iron handling by the transferrin receptor may contribute to the formation of free radical species which catalyze the lipid peroxidation of nigral cell membranes. We have assessed the number of transferrin receptors on membrane fractions prepared from the human striatum from control subjects and patients with Parkinson's disease. Equilibrium-binding studies demonstrated a reversible, saturable, and high-affinity transferrin binding site (KD = 3 nM) in human brain membranes. Regional binding assays indicate that the number of transferrin receptors in the putamen was reduced significantly in Parkinson's disease. The density of transferrin receptors was unaltered in membranes prepared from the caudate nuclei and the globus pallidus. To address the possibility that transferrin receptors are located on dopaminergic terminals, we have examined the distribution and number of transferrin receptors in the striatum of MPTP-treated mice using in vitro autoradiographic methods. In these experiments, the loss of dopaminergic terminals in the striatum was visualized by differential [3H]mazindol uptake site autoradiography. A marked reduction in the density of both transferrin receptors and [3H]mazindol binding sites was observed in the mouse striatum 7 days post-MPTP treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915738 TI - Sensory neurons of the rat sciatic nerve. AB - Experiments have been undertaken in this laboratory over recent years to accurately determine the numbers and sizes of somatic neurons which contribute to the normal sciatic nerve, at mid-thigh levels, of the adult, albino rat. This article is concerned with the dorsal root ganglion (DRG) neuron population of the sciatic nerve whose cell bodies were identified through retrograde labeling of cut branches of the sciatic with horseradish peroxidase (HRP) and/or its wheat germ conjugate (WGA-HRP). It is essential to understand the neuronal composition of the normal rat sciatic nerve if the consequences of aging, nerve injury, and surgical repair to improve functional regeneration are to be properly evaluated. Neuron counts were determined from camera-lucida paper drawings of all labeled profiles in DRGs L3-L6 at 100 x magnification. The profiles, obtained by labeling individual branches of the sciatic nerve (sural, lateral sural, tibial, peroneal, medial, and lateral gastrocnemius/soleus nerves) were traced from 40-microns thick, serial, frozen sections. The sizes of the perikarya, areas and diameters, were determined by tracing the perimeters of the drawn profiles on a digitizing tablet. The tablet's output was inputted directly into a specially designed computer spreadsheet which contained a mathematical table for correcting the split-cell error inherent to the sectioning process. Afferents from any given branch of the sciatic normally occupied two to three adjacent ganglia. Sciatic DRG neurons were normally located in lumbar ganglia L3-L6. Nearly 98-99% of all sciatic DRG perikarya resided in the L4 and L5 DRGs. The L6 DRG, traditionally regarded as an important contributor to the rat sciatic, contained merely 0.4% of its afferent neurons while the L3 ganglion, frequently overlooked as a contributor, contained 1.2% of the mid-thigh sciatic afferents. The mean size of rat DRG neurons was about 29 microns (550-600 microns2). The corrected counts revealed that the normal sciatic nerve (at mid-thigh levels), in rats between 2 and 12 months of age, contained a mean, total DRG neuron population of about 10,500 neurons. This is probably an underestimate by 3-5% of the true number due to occasional unreliable labeling of some of the small DRG neurons. It is estimated that the normal, mean number of sciatic DRG neurons of young to middle aged rats lies somewhere between 10,500 and 11,000 +/- 2000. The data suggest that nearly 20% of all DRG neurons in the sciatic nerve supply muscle afferents. The vast majority of the remaining neurons are involved with innervation of the skin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915739 TI - Plasmodium yoelii: antibody response in resistant and susceptible mouse strains. AB - The numbers of antigen-reactive antibody-secreting cells, levels of parasite antigen-specific serum antibodies and numbers of red blood cells staining positive for surface immunoglobulin were determined for susceptible and resistant mouse strains following infection with Plasmodium yoelii 17x. As a control, these parameters also were measured using antigen prepared from normal red blood cells. The relatively susceptible C57BL/6 mice produced more antigen-specific antibody secreting cells and had higher levels of immunoglobulin positive red blood cells than did DBA/2 mice, but the DBA/2 mice had more antigen-specific IgG in their sera. Both mouse strains possessed cells secreting antibody reactive with soluble normal red blood cell antigen; however, C57BL/6 mice had more IgG positive unparasitized RBC than did DBA/2 mice. Despite possessing fewer antibody positive normal RBC, DBA/2 mice had significantly higher levels of serum antibodies that reacted with soluble red blood cell antigen. These data indicate that levels of serum antibody may not reflect the amounts of antibody produced and that use of any single assay to assess the magnitude of the antibody response may give rise to misleading results. PMID- 1915740 TI - Trypanosoma cruzi in the opossum Didelphis marsupialis: parasitological and serological follow-up of the acute infection. AB - The opossum Didelphis marsupialis is known to be among the most important wild reservoirs of Trypanosoma cruzi and one in which the trypanosome may go through both the usual vertebrate intracellular cycle in its tissues and an extracellular cycle in the lumen of its scent glands. The species is highly resistant to heavy inocula and, depending on the parasite strain, experimental infections may be permanent or self limited. Aiming to understand the mechanisms involved in this parasite-host interaction we made a study of the acute phase of infection with different T. cruzi strains. Strains F, G-49 and G-327 produced durable infections with relatively high parasitemia and invasion of the scent glands, while equivalent inocula of the Y strain resulted in scanty parasitemia of short duration, no invasion of the SG, and no evidence of persistent parasitism. A smaller inoculum of G-49 produced only subpatent though persistent parasitemia and no invasion of the scent glands. The humoral immune response was less marked in the Y group; among the other groups IgM and IgG antibodies increased to high levels, higher in the G-49 group. The increase in IgG coincided with a drop of parasitemia to subpatent levels. Two opossums inoculated directly in the scent glands with culture forms of the Y strain had a short-lived subpatent parasitemia, but the parasites remained in the glands and serum Ig antibodies reached high levels. Immunoblot analysis showed that the sera of the inoculated opossums recognized few T. cruzi antigens (more in the F strain) in comparison with those of mice. However, with the only exception of those subcutaneously inoculated with the Y strain and including two naturally infected specimens, all the opossum's sera recognized a 90-kDa peptide in all T. cruzi strains. Our results confirm that opossums are able to selectively eliminate some strains of T. cruzi and indicate that the mechanism involved in this selection is probably not related to the humoral immune response. In infections by strains that are able to establish a permanent foothold in opossum tissues, there are indications that IgG antibodies participate in the control of the parasite population of the acute phase but are unable to prevent the chronic phase. It was once more demonstrated that the opossum infected scent glands function as diffusion chambers for parasite antigens but that, on the other hand, the parasites are here protected against the mechanisms developed by the host to control their population. PMID- 1915742 TI - Plasmodium falciparum: the calmodulin gene is not amplified or overexpressed in chloroquine resistant or sensitive isolates. AB - The in vitro growth of Plasmodium falciparum is sensitive to some calmodulin antagonists and these compounds show antagonism with classic antimalarials such as chloroquine suggesting competition for the same drug binding site. In order to ask if calmodulin is involved in resistance to chloroquine we cloned the calmodulin gene of P. falciparum. We show that it is encoded by a single gene and that the putative protein is highly homologous to calmodulin from other eukaryotes. The calmodulin gene is encoded on chromosome 14 and contains a single intron of 506 bp that has the appropriate donor and acceptor splice sites. Two major transcripts of similar size are encoded by this gene. The sequence of the gene is identical and the calmodulin protein is expressed approximately equally in chloroquine resistant and sensitive isolates of P. falciparum suggesting that alterations in this protein play no role in the mechanism of chloroquine resistance in the isolates tested. PMID- 1915741 TI - Trypanosoma cruzi: early resistance induced by culture-derived trypomastigotes. AB - Previous observations in this laboratory showed that injection of culture-derived trypomastigotes (CT), in CBA/J mice, induced an early increased resistance that was detected 24-72 hr after antigen injection and permitted mice to survive a challenge of 10(5) blood trypomastigotes (BT) corresponding to 2000 LD50%. Present experiments were conducted to determine the optimal conditions for inducing this early resistance and to investigate the early morphological changes which occurred in blood and lymphoid organs of mice infected with either BT or CT. Among nine antigens tested, only living CT showed a protective effect permitting most of mice to survive 30 days after BT challenge, while control mice injected with PBS or other antigens died at 10 +/- 1 days. A dose-response relationship was seen when different doses of CT were tested, higher doses of CT inducing higher survival and lower parasitemia. Injection of CT by either an im or ip route induced similar degrees of resistance but significantly different results were obtained when mice were challenged by using ip or im routes. Higher parasitemia and lower survival were always obtained when animals were challenged by the ip route. Within 72 hr, mice injected with BT presented a lymphopenia which reached a maximum at 48 hr, a depletion of thymic cortical zone, and splenomegaly with hyperplasia of the white pulp and congestion of the red pulp. No gross alterations were observed in animals infected with CT. Overall data suggest that the early resistance is a specifically induced phenomenon and that BT and CT induce different early reactions in the CBA/J lymphoid organs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915743 TI - Entamoeba histolytica: microtubule movement during mitosis. AB - The movement of microtubules (MTs) during nuclear division of Entamoeba histolytica was ultrastructurally studied. Regarding this MT movement, five stages of mitosis could be defined: prophase, metaphase, anaphase A, anaphase B, and telophase. In early stages of mitosis, chromatinic material appeared condensed, and MTs were detected in the center of the nucleus. Later, MTs seemed to grow from an electron-dense body located in the center of the nucleus. This body might be the microtubule organizing center, which organized the MTs, first in a lateral way, and later to form the mitotic spindle, which was made of a bundle of MTs joined by their ends. This junction of MTs to themselves could also be observed in cross-sections. The last stage of mitosis was the nuclear separation. Two different morphological types of intranuclear vesicles were also observed, which seemed to have different types of membrane. Both intranuclear vesicles were present during nuclear division, generally in clusters, and located close to the nuclear periphery. PMID- 1915744 TI - Schistosoma mansoni: eggshell formation is regulated by pH and calcium. AB - The protein precursors of the schistosome eggshell are synthesized and packaged into secretory vesicles in the vitelline cells. These vesicles appear to contain an emulsion of eggshell precursor material. Evidence is presented to show that these secretory vesicles are acidic as in other systems and that this acidity stabilizes the emulsion and prevents the eggshell cross-linking reactions from occurring. Alkalinizing treatments trigger eggshell formation within the secretory vesicles as shown by (1) the induction of autofluorescence and (2) by electron microscopy which shows that the eggshell precursors have aggregated within the secretory vesicles into spherical particles bearing microspines. These aggregates formed in the secretory vesicles were isolated and shown to have the same protease resistance and amino acid composition as authentic eggshell. The calcium ionophore A23187 induces scattered autofluorescence in intact female worms which electron micrographs show to be due to exocytosis of eggshell material. Based on these observations we propose a model for the formation of schistosome eggshell and suggest that it may apply to all trematodes in which the eggshell precursors are present as stable emulsions in the secretory vesicles of the vitelline cells. PMID- 1915745 TI - Detection of polymerase chain reaction-amplified malarial DNA in infected blood and individual mosquitoes. AB - Chelex treatment of Plasmodium falciparum and P. berghei infected tissues, in lieu of organic extraction, was followed directly by polymerase chain reaction amplification of primed circumsporozoite gene sequences. The amplified DNA products were detected in stained gels and hybridization blots of extracts from individual infected mosquitoes and dissected mosquito tissues as well as small volumes of infected blood. Parasite development, within the mosquito midgut and salivary gland, was also monitored as a function of time post infectious blood meal. The temporal presence of amplifiable circumsporozoite gene sequences in the infected mosquito midgut lumen, midgut endothelium, and salivary glands corresponded directly to the visual identification of ookinetes, oocysts, and salivary gland sporozoites, respectively. PMID- 1915746 TI - Plasmodium falciparum: an invasion inhibitory human monoclonal antibody is directed against a malarial glycolipid antigen. AB - A Plasmodium falciparum malaria blood stage antigen was detected using a human monoclonal antibody (MAb A52A6) obtained from a clinically immune donor. Immunofluorescence analysis showed that the MAb reacted with the intracellular parasite throughout the asexual blood stage cycle as well as with gametocytes. The MAb also reacted with the surface of erythrocytes containing late stage P. falciparum parasites. The antigen seen by the MAb was species- but not strain- or isolate-specific. At rupture of the infected erythrocytes, antigenic material was deposited on the membrane of uninfected cells surrounding the parasite. At merozoite invasion MAb reactive material was present on the invaginating erythrocyte membrane, indicating an involvement of the antigen in the invasion process. This was also indicated by the high capacity of the MAb to inhibit merozoite invasion in vitro. The antigen appears to be a phosphoglycolipid, sensitive to phospholipase and present in lipid extracts of P. falciparum infected erythrocytes. PMID- 1915747 TI - Leishmania donovani: long-term culture of axenic amastigotes at 37 degrees C. AB - L. donovani promastigotes were subjected to heat treatment yielding an axenic amastigote stage which was long-term cultured at 37 degrees C. No differences were observed between the growth rates of axenic amastigotes and promastigotes. Flow cytometry-derived DNA histograms of axenic amastigotes and promastigotes were typical of exponentially growing cell populations. Moreover, axenic amastigotes were metabolically active as evidenced by the release of an immunoprecipitable extracellular acid phosphatase (SAcP) into their culture supernatant. Cell transformation was confirmed by transmission electronmicroscopic examination of thin sections and extended by fracture-flip survey which allowed differentiation of cell membranes. The ultrastructure and nanoanatomy of axenic amastigotes was identical to that of intracellular amastigotes. The production of large amounts of heat-shock axenic amastigotes suitable for biochemical and biological studies of differentiation in Leishmania donovani may have important implications in the development of prevention and/or treatment strategies. PMID- 1915748 TI - Onchocerca volvulus: application of the polymerase chain reaction to identification and strain differentiation of the parasite. AB - Previous studies have demonstrated that the genome of Onchocerca volvulus contains a variable tandemly repeated DNA sequence family with a unit length of 150 bp. The variability of the 150-bp family has been exploited to develop O. volvulus strain and species specific DNA probes. Application of these DNA probes to the study of the epidemiologically most significant life cycle stages of the parasite has been confounded by several obstacles. These include the relative insensitivity of some of the DNA probes and the difficulty in releasing genomic DNA from infective larvae and skin microfilariae in a form that may be directly detected by hybridization to the probes. DNA sequence comparison of 18 known examples of the 150-bp repeat has been used to develop two populations of degenerate oligonucleotides. These oligonucleotides have been shown to support the amplification of the 150-bp repeat family from Onchocerca DNA, using the polymerase chain reaction. Both strain and species specific members of the repeat family are faithfully amplified, allowing characterization of a parasite on the basis of hybridization of the PCR amplification products to the previously developed DNA probes. This method is shown to be applicable to all diagnostically important forms of the parasite, including adults, infective larvae, and skin microfilariae. In addition, the method is capable of detecting O. volvulus infective larvae directly in extracts of blackfly vectors. PMID- 1915749 TI - Angiostrongylus costaricensis: culture of third-stage larvae to young adults in a defined medium. AB - The third-stage larvae of Angiostrongylus costaricensis were successfully cultured to young adults in a chemically defined medium. The most suitable medium for the development was Waymouth's medium among eight defined media examined. Twenty-eight days after cultivation in this medium, 77% of the larvae developed to young adults, although these worms gradually died thereafter. When Waymouth's medium was supplemented with mouse red blood cells, these young adult worms continued their development. The mean body lengths of the worms cultivated in Waymouth's medium supplemented with RBCs were significantly larger than those of the worms in the medium without RBCs on Days 14 and 21 after cultivation. Addition of RBCs was essential for their further development. At 28 days after cultivation, the maximum body length of the worms was 2.1 mm for males and 3.3 mm for females. Additions of serum, yeast extract lactalbumin hydrolysate, and growth factors to Waymouth's medium did not provide any additional benefits for worm development. PMID- 1915750 TI - Plasmodium falciparum: the effect of pH and Ca2+ concentration on the in vitro cytoadherence of infected erythrocytes to amelanotic melanoma cells. AB - Cytoadherence of Plasmodium falciparum-infected erythrocytes to amelanotic melanoma cells was pH dependent; increased adherence was observed in the pH range of 6.1 to 6.8 and was greatest between pH 6.6 and 6.8 Ca2+ promoted cytoadherence, but at higher concentrations (40-50 mM) than is usually the case for cell-cell adhesion. The effects of pH and Ca2+ were interdependent--the pH optimum of cytoadherence was altered by the Ca2+ concentration in the medium. The adherent properties of several P. falciparum lines (including a knobless cytoadherent line) under varying pH and Ca2+ concentrations were similar. PMID- 1915751 TI - Leishmania donovani: characteristics of adenosine and inosine transporters in promastigotes of two different strains. AB - The nucleoside transport characteristics of two strains of Leishmania donovani promastigotes were studied. Strain S1, growing in fully defined medium, and strain S2 (MHOM/ET/67/HA3) both transported adenosine and inosine, but only strain S1 transported uridine and thymidine. Competition studies in the presence of 100 microM of unlabeled adenosine, inosine, guanosine, 2'-deoxyadenosine, tubercidin, formycin B, 3'-deoxyinosine as well as uridine, thymidine and cytidine, with either 1 microM [3H]adenosine or [3H]inosine as permeant, were carried out. The inhibition profile with [3H]inosine as permeant was essentially identical in S1 and S2 promastigotes, indicating that the same inosine transporter was present in both strains. However, with [3H] adenosine as permeant, significant differences were noted between the two strains. Thus, only adenosine, 2'-deoxyadenosine, tubercidin, uridine, and thymidine were strongly inhibitory in S1 promastigotes, while essentially all nucleosides tested were effective in S2 promastigotes. This indicates that adenosine transport in S2 promastigotes seems to involve a transporter differing from that described for S1 promastigotes. PMID- 1915752 TI - Ascaris suum: stage-specific differences in lectin binding to the larval cuticle. AB - A glycosylated component with affinity for wheat germ agglutinin (specific binding to n-acetyl-D-glucosamine monomers and oligomers) and weak affinity for poke weed mitogen (specific binding to n-acetyl-D-glucosamine oligomers) was detected temporally on the surface of Ascaris suum larvae developing in vitro and on in vivo-derived larvae. The component was identified on the surface of in vitro-derived late second stage larvae, on all late third stage larvae (derived from pig lung), and all fourth stage larvae (obtained from pig intestines and from in vitro culture) of A. suum. None of the newly hatched first molt, L2, or early L3 bound any of the lectins tested. The component exhibited no affinity for concanavalin A (specific binding to alpha-D-mannosyl and alpha-D-glucosyl residues) or Dolichos biflorus lectin (specific binding to n-acetyl-D galactosamine). A component with similar lectin binding specificities had previously been found on the cuticle of adult A. suum. PMID- 1915753 TI - Schistosoma mansoni: a simple method for the extraction of DNA from single worms for PCR amplification. PMID- 1915754 TI - Leishmania donovani: use of two different, commercially available, chemically defined media for the continuous in vitro cultivation of promastigotes. PMID- 1915755 TI - Morphological studies on the effect of L-leucine methyl ester on mouse peritoneal macrophages in vitro. AB - Mouse peritoneal macrophages (MO) were treated in culture with 5 mM L-leucine methyl ester (L-Leu-OMe), for 5, 10, 20, 40, and 60 min. The treatment resulted in rapid vacuolisation of the cytoplasm due to the dilatation and disruption of lysosomes. Autophagy caused by lysosomal enzymes destroyed most of the cytoplasmic organelles by 40 minutes after L-Leu-OMe treatment, but the cell membrane and nucleus were in many MOs resistant to the damage. 60 min after L-Leu OMe treatment most of the MOs were killed. It is supposed that the disruption of the lysosomes is caused by formaldehyde produced by the hydrolysis of L-Leu-OMe. PMID- 1915756 TI - The nominal section thickness--importance of their correction for morphometry. AB - The real finite section thickness of histologic slices is one of the dominant artefacts in morphometrical studies. Investigations without correction of the section thickness error are not reproducible or comparable. On this basis we measured the real finite section thickness of histologic slices with a nominal section thickness of 2, 4 and 6 microns with a microinterferometrical method. We also estimated the size of the error of a fictive volume density and a fictive Sholpo-correction. On the nominal section thickness of 2 and 6 microns we determined significant differences between the nominal section thickness and the real finite section thickness. We found analogue differences in the estimation of the fictive volume densities and in the fictive Sholpo-corrections. We did not determine a significant difference between the real finite and the nominal section thickness for the nominal section of 4 microns. We also could not determine significant differences between the real and nominal fictive volume densities and Sholpo-corrections. The measurement errors are discussed, and a test of reproducibility was performed. PMID- 1915757 TI - Relation between renal and hepatic excretion of drugs: XV. Organ distribution and transport of the new antiarrhythmic drug Bonnecor in kidney and liver of rats. AB - Following administration of various doses of 14C-labeled Bonnecor (0.15 to 0.6 mg/100 g b.wt. i.v.) renal excretion of 14C-radioactivity dominates and the total rate of excretion both via kidney and liver reaches 60% during 6 h clearance experiment, independent of the administered dose. Otherwise nearly the same concentration of 14C-radioactivity can be measured in kidney and liver tissue. An alpha- und beta-slope of disappearance from the tissue seems to exist. At different times after administration of Bonnecor (0 to 15 h) the concentrations in kidney and liver tissue are distinctly higher compared with plasma concentrations. In vitro experiments on tissue slices confirm a nearly identical degree of accumulation of 14C-radioactivity in liver and kidney. In renal cortical slices the high degree of accumulation depends on active tubular transport processes. Comparing accumulation in liver slices under aerobic and anaerobic conditions a preferential passive uptake of Bonnecor can be demonstrated. Efflux kinetics in slices from liver and kidney cortex is in accordance with this interpretation. PMID- 1915758 TI - Effect of the microbial constituents, LPS and BCG, on the glycosaminoglycans of chondrocyte cultures. AB - Earlier we reported that articular chondrocytes in monolayer culture produce pericellular proteoglycans both with short and long half lives, T-1 and T-2 (Kittlick et al. 1991 b). Now monolayer cultures have been investigated to assess the influence on the metabolism of pericellular proteoglycans or glycosaminoglycans by lipopolysaccharide of E. coli and S. typhimurium as well as by Bacillus Calmette-Guerin. PMID- 1915760 TI - Chondrocytes may activate macrophages. AB - It is demonstrated that conditioned media of articular chondrocytes cultured with Bacilli Calmette-Guerin are capable of activating macrophages. This activation reaches different levels and is expressed both by different cell survival and enhanced synthesis of glycosaminoglycans that remain cell-associated (exp. group III) or are secreted (exp. group II). The reason of these variances is unknown. - A protein factor is supposed to be present in variable concentration or activity. Interleukin-1 could not be correlated with the results. PMID- 1915759 TI - Studies on lipid peroxidation in pancreatic tissue. In vitro formation of thiobarbituric-acid-reactive substances (TBRS). AB - In pathogenic studies on acute pancreatitis the importance of a temporary ischemia on induction of autodigestion was demonstrated. Because of the involvement of oxygen-derived free radicals in the ischemia/reperfusion injury of other tissues we have investigated the influence of artificial oxidants, as FeCl3 and H2O2, on pancreatic tissue and isolated pancreatic acinar cells. Lipid peroxidation was determined as thiobarbituric-acid-reactive substances (TBRS). In these experiments the TBRS concentration was elevated within the first min of incubation with FeCl3. The exposure of pancreas homogenates and intact acinar cells to H2O2 had no remarkable effect on formation of TBRS. Under this condition the survival of cells was strongly reduced, while cells exposed to FeCl3 revealed a remarkably slower rate of cytolysis. The missing correlation between cell lysis and elevation of TBRS suggests that lipid peroxidation might not be essential process in pancreatic acinar cell damage. PMID- 1915761 TI - Changes in the activities of jejunal glucosidases in experimental intestinal tumorigenesis induced by 1,2 dimethylhydrazine in rats fed different diets. AB - The purpose of the present study was to establish the effect of the carcinogen 1,2 dimethylhydrazine on the activities of the jejunal glucosidases and to assess the possible modifying effect of different diets. Two control groups of Wistar albino rats were used - fed standard pellet diet and fed the same diet + 1,2 dimethylhydrazine treatment. Six experimental groups treated with 1,2 dimethylhydrazine were provided. One of them was fed standard diet, containing 30% of wheaten bran and the other 5 groups received high-lipid diets, containing 30% of different fats. The rats were injected subcutaneously once a week for 12 weeks with 20 mg 1,2 dimethylhydrazine/kg b.m. and left for 12 weeks in order to develop a tumor growth. The activities of 5 glucosidases (lactase, maltase, sucrase, palatinase and cellobiase) were determined in homogenates from jejunal mucosa taken near by the tumors and in homogenates from the tumors themselves. An expressed decrease of the jejunal glucosidase activities near the tumors and in the tumors was established. The animals fed 30% wheaten bran diet did not develop tumorigenesis and showed comparatively slight decrease of the enzyme activities. In general, the high-fat regimens did not exert such a preventive effect. PMID- 1915762 TI - Host recognition by toxigenic plant pathogens. AB - Certain fungal pathogens release host-selective (or host-specific) toxins (HST) as a host recognition factor during spore germination at the infection site on plants. Prior to penetration of the pathogen into its host, the released toxin specifically binds to a putative receptor on the host cells and initiates signaling mechanisms leading to pleiotropic effects on cells. Of these, the crucial one negates the general and inducible defense reactions of the cells. This is accomplished by a signal from the HST, which is transduced through a path way at or near the step of plasma membrane modulation, which is directly or indirectly triggered by the HST. This mechanism operates even though the toxin may affect mitochondria or chloroplasts as the primary target organelle. The fungal spore is able to penetrate the so-called 'narcotized cell' and completes the initial colonization of the host. The host recognition process may take place without necessitating host cell death, even in the case of perthophytic parasites. At the molecular level, HST-mediated recognition of the host by a pathogen requires strict stereochemical precision like a lock and key. PMID- 1915763 TI - Implications of toxins in the ecology and evolution of plant pathogenic microorganisms: bacteria. AB - This review attempts to rationalise what is known about bacterial phytotoxins and associate it with the ecology and possible evolution of the producing organisms. Study of non-toxin producing variants gives insight into the ecological role of the toxin. Elucidation of chemical structures of phytotoxins has shown that many exist as families of analogous compounds. Studies on the variation of chemical structures and how they are distributed across species and genera can lead to development of hypotheses on evolutionary relationships. Knowledge on biosynthetic pathways to toxins allows recognition of specific enzymatic steps involved in developing the characteristic features of the structures. Phytotoxins often have a potent biochemical activity, and in some cases the producing organism has associated mechanisms to prevent action of the toxin upon itself; in such cases toxigenesis is clearly not a chance event. The various aspects of bacterial toxigenesis indicate that bacterial phytotoxins are special secondary metabolic products that play beneficial roles to the producing organisms in their various ecological niches. PMID- 1915764 TI - On the mechanism of the involvement of endothelium in reactive hyperemia. AB - Experiments on anesthetized dogs and on vascular test-preparations demonstrated that reactive hyperemia (RH) was accompanied by the appearance of vasodilator in the blood, and that the level increased with the duration of occlusion of the artery. Removal of the endothelium of the part of the vascular bed studied using saponin, decreased the RH and relaxation of a test-preparation. A rise of pressure in the vascular bed, and a decrease in the deformability of the endothelium resulting from pretreatment with dimerized glutaraldehyde, affected both the hyperemia and the reaction of the vascular preparation in a similar way. It was concluded that the RH resulted from the secretion of vasoactive substances by the endothelium in response to a fall in intravascular pressure. PMID- 1915765 TI - Effect of vasoactive amines on Weibel-Palade bodies in capillary endothelial cells. AB - The presence and distribution of Weibel-Palade bodies in stomach and colonic mucosal microvessels after the administration of vasoactive amines (serotonin and histamine), the serotonin depletor reserpine, and the von Willebrand factor secretagogue thrombin, was studied by transmission electron microscopy. These agents elevated the number of Weibel-Palade bodies in all microvascular endothelial cells and especially in capillaries. It is concluded that vasoactive amines enhance the synthesis and secretion of large von Willebrand protein multimers by endothelial cells. PMID- 1915767 TI - Vidalols A and B, new anti-inflammatory bromophenols from the Caribbean marine red alga Vidalia obtusaloba. AB - Chemical studies of the Caribbean red alga Vidalia obtusaloba have resulted in the isolation of two new bromophenolic metabolites, vidalols A and B (1, 2). The new compounds were discovered as part of an organized effort to isolate new naturally-occurring anti-inflammatory agents with a focus upon those which may function through the inhibition of phospholipase A2. PMID- 1915766 TI - Altered brain cholinergic enzymes activity in the genetically obese rat. AB - Genetically obese male Zucker rats (fa/fa) and their lean littermates (Fa/-) were used in this experiment. Fourteen-week-old obese and lean littermates were sacrificed and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) enzymes were assayed in specific brain regions. The assays of these enzymes indicate that obese animals had a significantly lower ChAT activity in the cerebellum, pons, and cerebral cortex and a significant increase in ChAT activity in the thalamus and hypothalamus. Meanwhile, the cerebral cortex, cerebellum, midbrain, thalamus and hypothalamus of the obese animals showed significantly higher AChE activity than their lean littermates. It was concluded from this study that obesity may be associated with changes in the enzymes of the brain cholinergic system. PMID- 1915768 TI - Transgenic vertebrates. Introduction. PMID- 1915769 TI - Transgenic regulation in laboratory animals. AB - This chapter is an attempt to summarize some commonly accepted and some more subjective opinions about the regulation of transgene expression in laboratory animals. After a short historical introduction, I present some general notions regarding gene structure/function. The spotlight shifts then to the description of the most popular techniques for gene transfer, including the targeted gene replacement. The different approaches are briefly discussed in terms of intrinsic advantages and limitations regarding gene expression patterns. Furthermore, the role of enhancers, promoters and other cis-acting elements such as silencers and dominant control regions as well as their involvement in the chromatin on-off state are discussed on the basis of a specific example studied in our laboratory. The review concludes by presenting recent results and the new perspectives opening in the field of 'surrogate' (also called 'reversed') genetics. Some problems which remain to be solved both at the technical as well as at the social ethical level are also briefly presented. PMID- 1915770 TI - Analysis of the immune system with transgenic mice: B cell development and lymphokines. AB - Over the last decade transgenic mice expressing genes relevant for the immune system have been generated. Transgenic expression of immunoglobulin heavy and/or light chain genes of different isotypes and different specificities have helped to better understand phenomena relevant to B cell development such as allelic exclusion of immunoglobulins and B cell tolerance. Transgenic mice expressing interleukin genes have also been used to study the ways of action of these important growth and differentiation factors in the context of the mouse immune system. PMID- 1915771 TI - Analysis of the immune system with transgenic mice: T cell development. AB - Transgenic mice carrying functionally rearranged T cell receptor genes have contributed significantly to our knowledge of T cell development and thymic positive and negative selection processes. In addition, TCR-transgenic mice have been used to investigate mutations affecting thymocyte development, like scid and lpr. Gene targeting by homologous recombination will allow to analyze more specifically the molecular mechanisms underlying thymic selection and peripheral tolerance. PMID- 1915773 TI - Production of transgenic birds. AB - The avian embryo presents a tremendous challenge for those interested in accessing and manipulating the avian germ line. By far the most successful method of gene transfer is by retrovirus vector. The efficacy of retrovirus vectors has been demonstrated by germ line insertion of replication-competent retroviruses as well as the insertion of replication-defective retrovirus vectors carrying bacterial marker genes. Retroviral vectors have also been shown to be useful for the transfer and expression of genes in somatic cells. Further, germ line transgenesis has been reported in both the chicken and the Japanese quail. In addition, several alternative gene transfer methods are under development. These include transfection of avian sperm, development of germ line chimeras using primordial germ cells and blastodermal cells, and the development of embryonic stem cell lines. Potentially, basic research and the poultry industry will derive substantial benefit from this revolutionary technology. PMID- 1915772 TI - Transgenesis in fish. AB - Gene transfer into fish embryo is being performed in several species (trout, salmon, carps, tilapia, medaka, goldfish, zebrafish, loach, catfish, etc.). In most cases, pronuclei are not visible and microinjection must be done into the cytoplasm of early embryos. Several million copies of the gene are generally injected. In medaka, transgenesis was attempted by injection of the foreign gene into the nucleus of oocyte. Several reports indicate that the injected DNA was rapidly replicated in the early phase of embryo development, regardless of the origin and the sequence of the foreign DNA. The survival of the injected embryos was reasonably good and a large number reached maturity. The proportion of transgenic animals ranged from 1 to 50% or more, according to species and to experimentators. The reasons for this discrepancy have not been elucidated. In all species, the transgenic animals were mosaic. The copy number of the foreign DNA was different in the various tissues of an animal and a proportion lower than 50% of F1 offsprings received the gene from their parents. This suggests that the foreign DNA was integrated into the fish genome at the two cells stage or later. An examination of the integrated DNA in different cell types of an animal revealed that integration occurred mainly during early development. The transgene was found essentially unrearranged in the fish genome of the founders and offsprings. The transgenes were therefore stably transmitted to progeny in a Mendelian fashion. Southern blot analysis revealed the presence of possible junction fragments and also of minor bands which may result from a rearrangement of the injected DNA. In all species, the integrated DNA appeared mainly as random end-to-end concatemers. In adult trout blood cells, a small proportion of the foreign DNA was maintained in the form of non-integrated concatemers, as judged by the existence of end fragments. The transgenes were generally only poorly expressed. The majority of the injected gene constructs contained essentially mammalian or higher vertebrates sequences. The comparison of the expression efficiency of these constructs in transfected fish and mammalian cells indicates that some of the mammalian DNA sequences are most efficiently understood by the fish cell machinery. Chloramphenicol acetyl transferase gene under the control of promoters from Rous sarcoma virus, and human cytomegalovirus, was expressed in several tissues of transgenic fish. Chicken delta-crystallin gene was expressed in several tissues of transgenic fish.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1915774 TI - Production of pharmaceutical proteins in milk. AB - There is every reason to expect that it will be possible within the next few years to begin to use farm animals to produce large quantities of some of the human proteins that are needed for the treatment of disease. Revolutionary new opportunities for the production of novel proteins in milk have been created by the development of methods for gene transfer. Exploitation of these opportunities depends upon selection and cloning of milk protein genes and identification of the sequences that govern tissue specific hormonally induced expression in the mammary gland. Studies with three genes, ovine beta-lactoglobulin, rat beta casein and whey acidic protein of rat and mouse, suggest that they may all meet this requirement. Fragments of the ovine beta-lactoglobulin, murine whey acidic protein and rabbit beta-casein genes have directed production of novel proteins in the milk of transgenic mice, sheep, rabbits and pigs. The proteins were biologically active and usually co-migrated with authentic proteins. In early experiments, protein concentration was low, but our recent observations suggest that fusion genes containing genomic clones direct production of concentrations of protein that are suitable for commercial exploitation. In the longer term, two approaches may offer the potential of more reliable expression. Control elements capable of directing expression that is independent of site of insertion of the gene, but dependent on the number of copies of the gene, have been identified for a small number of genes. The availability of such elements for the milk protein genes would increase the reliability of gene expression considerably. Alternatively, targeted mutation of genes may allow the insertion of coding sequences within an existing gene so avoiding position effects. PMID- 1915775 TI - The genetic engineering of production traits in domestic animals. AB - The transfer of recombinant DNA by microinjection of embryo pronuclei provides a novel approach to the manipulation of production traits in domestic animals. In this review, several of the key areas currently under investigation are examined and their progress evaluated. These include the manipulation of the endocrine system by altered growth hormone genes and the modification of animal biochemistry by the introduction of the cysteine biosynthetic pathway and the glyoxylate cycle. The possibilities inherent in the alteration of structural proteins important to domestic animal productivity, and some ethical issues relevant to the release of modified animals are also considered. The experimental information obtained so far in the area indicates that transcriptional regulation of the genes and a thorough understanding of the physiological processes involved are both important factors in the practical application of the technique to the improvement of animal productivity. PMID- 1915778 TI - Electrophysiological study of interaural sound intensity difference in the dolphin Inia geoffrensis. AB - A wave observed in the auditory brainstem responses (ABR), sensitive to the side of sound presentation, is described in a dolphin (Inia geoffrensis). Dependence of the wave threshold on location of the sound source showed that the interaural intensity difference was more than 20 dB. PMID- 1915777 TI - Transgenic vertebrates. Conclusions and outlook. PMID- 1915776 TI - Disease resistance in farm animals. AB - Genetic variations in disease resistance of farm animals can be observed at all levels of defence against infectious agents. In most cases susceptibility to infections has polygenic origins. In domestic animals only a few instances of a single genetic locus responsible for disease resistance are known. A well examined example is the Mx1 gene product of certain mice strains conferring selective resistance to influenza virus infections. Attempts to improve disease resistance by gene transfer of different gene constructs into farm animals include the use of monoclonal antibody gene constructs, transgenes consisting of antisense RNA genes directed against viruses and Mx1 cDNA containing transgenes. PMID- 1915779 TI - Insulin acts on the hypothalamic glucose-facilitated neurons to induce hyperglycemia and hyperinsulinemia in the rat. AB - Microinjection of insulin (0.04-0.12 IU/microliter) into the anterior hypothalamus or the lateral hypothalamus, but not the ventromedial hypothalamus of the rat brain, caused a dose-dependent rise in blood glucose and in serum insulin. The majority (71.5%) of the glucose-facilitated neurons recorded in the lateral hypothalamic area were excited by intracerebral injection of insulin. The data indicate that insulin acts on the hypothalamic glucose-facilitated neurons to induce hyperglycemia and hyperinsulinemia. It is unknown whether insulin normally reaches the hypothalamic area, or how it might do so. PMID- 1915780 TI - Reevaluation of hydropathy profiles of voltage-gated ionic channels. AB - A reevaluation of the secondary structure of Na, Ca and K channel proteins led to the following results. Only three segments (S1, S5 and S6) of each repeat are sufficiently hydrophobic to be predicted as transmembrane helices, if a window of 19 amino acids is used. Some of the S2 and S3 segments show higher hydrophobic values when calculated with the window of 9 amino acids and can be predicted as short helices. S4 segments are strongly hydrophilic and cannot be predicted as transmembrane helices. Some of the S2, S3 and S4 segments have an amphipathic character; however, these helices do not span a membrane. A model is proposed where 12 hydrophobic transmembrane helices surround 12 shorter helices, forming a hydrophilic pore. In addition, a unique pattern for S4 segments of voltage-gated channel proteins is defined. PMID- 1915781 TI - An improved test for Africanized honeybee mitochondrial DNA. AB - Mitochondrial DNA derived from Apis mellifera scutellata, the ancestor of the Africanized bees of the New World, lacks a BglII restriction site found in other types of honeybee. We present primers allowing amplification of a 485-bp section of the cytochrome b gene containing this site, using the polymerase chain reaction. Digestion of the amplified product with BglII yields contrasting patterns between Africanized and other honeybees. PMID- 1915782 TI - Schistosoma mansoni: a chemoattractive factor released by males and its receptor in females. AB - Chemoattraction between developing (23- to 28-day-old) and adult (10- to 12-week old) Schistosoma mansoni males and females has been described previously. We report here on in vitro attraction of mature worms to released products of worms of the opposite sex. In the absence of a stimulus worms migrated randomly and did not show any preference in their orientation. Males were not significantly attracted to released products of females. Females exhibited greatest attraction to released products of males, and some attraction to the lipid fraction of released products of males. The aqueous fraction of male-released products slightly repelled females. Prior exposure to released products of males rendered females unresponsive to subsequent exposure, suggesting receptor saturation. These findings have important potential implications for the control of schistosomiasis by intercepting attraction and mating between males and females. PMID- 1915783 TI - Epidemiology and risk factors of pneumonia in critically ill patients. Intensive Care Unit Group for Infection Control. AB - Risk factors for pneumonia were analysed in a large population of critically ill patients, collected in two prospective multicentre "pneumonia studies" in Italy. Twenty-three intensive care units were involved and the study time was 150 unit months. Only patients without previous pulmonary infection, with intensive care unit stay greater than or equal to 48 hours and no rapidly irreversible illness at admission were included. The incidence of pneumonia in the 1475 selected patients was 15% (220 cases). 239 patients died in ICU; the mortality rate was significantly higher in patients developing pneumonia (p less than 0.0001); pneumonia was found to be an independent highly significant risk factor for death in critically ill patients (OR = 3.88; p less than 0.0001). Multivariate analysis of seven risk factors for pneumonia showed a significantly higher risk in patients with neuromuscular disease (OR = 3.8, p less than 0.002), impairment of airway reflexes at admission (OR = 2.93, p less than 0.0001), and greater than or equal to 24h respiratory assistance (OR = 3.05, p less than 0.0001). Impairment of airway reflexes at admission to the emergency room or intensive care unit identifies the population who will experience 3/4 of the overall lower respiratory tract infections. Rapid recognition of at-risk patients seems clinically important and may improve awareness programs and preventive approaches. PMID- 1915785 TI - The inappropriateness of conventional use of the correlation coefficient in assessing validity and reliability of dietary assessment methods. AB - Accuracy and precision of nutritional data are crucial in estimating effects in nutritional epidemiology. Because it is known that such data are usually flawed, studies have been designed to estimate both the validity of diet assessment methods in measuring "true" diet and the reliability of these methods in providing nutrient data that are at least reproducible. In these studies, validity and reliability have often been gauged by computing correlation coefficients between two or more estimates of diet and testing the coefficient's departure from 0. We propose that the correlation coefficient may be inappropriate in these studies as a measure of association. If correlation coefficients are presented, we suggest that one should also present confidence intervals and test the departure of the coefficient from approximately 1 rather than 0. We have examined this approach using dietary data from various studies. We have computed 95% confidence intervals of the correlation coefficients and have tested H0:rho = 0.95 as an approximation of rho = 1.00. In all of the studies selected, comparisons produced correlation coefficients statistically significantly different from both 0.95 and 0. Due to the dependence of the correlation coefficient on factors unique to individual studies, it is recommended that other techniques be used to assess agreement between nutrient scores derived in reliability or validation studies. Viable options include linear regression, analyses of the standard deviations of the differences between scores, and examinations of the intraclass correlation coefficient. PMID- 1915787 TI - The use of AIDS surveillance data for short-term prediction of AIDS cases in Madrid, Spain. AB - The paper presents a preliminary attempt to predict the numbers of AIDS cases in the Community of Madrid (CAM) up to 1992. Using AIDS case surveillance data gathered by CAM, and a statistical procedure that includes a distribution for reporting delays, the numbers of new diagnoses, reports, AIDS deaths and numbers of patients alive is predicted. Approximate confidence limits for the numbers of new diagnoses are given. We emphasise that these predictions are tentative given the nature of the reporting delays, and discuss the use of such predictions and the requirements for their improvement. PMID- 1915784 TI - Antigens of the Mycobacterium avium, Mycobacterium intracellulare complex. AB - In the past decade, the clinical significance of the Mycobacterium avium, Myobacterium intracellulare complex (MAC) has increased dramatically primarily because of the association between the MAC and the acquired immunodeficiency syndrome (AIDS). Recent hospital reports have suggested that about one-half of AIDS patients in the United States are infected with the MAC. The resulting myobacteremia is a primary cause of mortality in 5-10% of these patients. This increased clinical importance of the MAC has generated renewed interest in MAC immunobiology. In this review, recent immunological and biochemical characterizations of four classes of dominant myobacterial antigens - glycopeptidolipids, arabinogalactan, lipoarabinomannan and MAC proteins - is examined. In addition, future prospects for improved diagnosis of MAC disease using defined monospecific antigens is discussed. PMID- 1915786 TI - On the interaction of Trypanosoma cruzi neuraminidase and human lipoproteins. AB - Binding and penetration of Trypanosoma cruzi to host cells is a process that preludes infection and is mediated by specific recognition molecules. Neuraminidase is one of the parasite molecules involved in infection and, in this review, we describe some of its biochemical characteristics, its interaction with human lipoproteins and its effect on infection of mammalian cells. PMID- 1915788 TI - Epidemiology of infant deaths due to congenital malformations: Italy 1958-1981. AB - The spatial and temporal distribution of infant death rates attributed to the single cause of congenital malformation (DCM) in Italy was studied for the period 1958-1981. Variation of DCM rates in this period was investigated for the whole country, for the three main geographical areas of the North, Center, and South, and for each of the 18 Italian regions (there are 20 administrative regions, but in this study Abruzzo were pooled with Molise and the Aosta Valley with neighbouring Piedmont). It was found that DCM decreases significantly with time. The decrease is considerable in the North and the Center of the country, whereas in the South temporal variation is minimal. There is a marked decrease of the variance of the DCM rates between regions with later years, possibly indicating a tendency to equalization of environmental effects in a large part of the peninsula. PMID- 1915789 TI - Flash flood disaster--Nimes, France, 1988. AB - On October 3, 1988, at 7:45 a.m. a flash flood occurred in the region of Nimes, France. Though the homes of 45,000 people were damaged and more than 1,100 vehicles were destroyed, only 3 severe injuries and 9 deaths were reported. A community survey was conducted to study (1) what factors might have contributed to the limited number of deaths, (2) the reactions of the population to the disaster, and (3) the health effects associated with the impact and postimpact phases of the disaster. Overall, 108 questionnaires were completed from a systematic sample of 187 households living in ground-level dwellings in two of the most seriously affected areas of the city. Only 17% of all interviewees knew that they lived in an area subject to flood. When they realized they were in danger, 93% of all persons were in their houses or other buildings, 4% were in the streets, and 3% were in cars. Fifty-six percent of the interviewees tried to get to safety. Thirty percent of the interviewees reported that they were rescued; 20% of these persons reported being saved from a direct life threat. Neighbors (40%), family members (20%), firefighters (12%), the Red Cross (10%), and military personnel (8%) conducted rescue operations. Six percent of all members of interviewed households were reportedly suffering mild injuries that, in 70% of these cases, had been sustained during the impact phase. Health problems and injuries during the postimpact phase may have been limited by the response of trained military personnel and by the distribution of boots and gloves to other responders.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915791 TI - A seroepidemiological survey on Leishmania infantum infection. AB - Findings from a seroepidemiological survey of Leishmania infantum (LI) infection are presented. Among residents in the province of Rome, 2.7% (4.4% in the city of Rome and 1% in the suburbs) of 374 adults were positive for specific LI antibodies in indirect haemoagglutination studies. Among 217 adult residents of Caltanissetta province (Sicily), 4.1% were positive for LI antibodies (4.2% in Caltanissetta city and 4% in the suburbs). Serological tests for LI antibodies were also carried out on stray dogs captured in Rome. 5% of them resulted positive. Our findings show that LI infection is moderately present in both Rome and Caltanissetta, the latter being an area of known endemicity. According to our data, LI infections are usually asymptomatic: none of the positive subjects had a history of visceral leishmaniasis, and none of the seropositive dogs showed any sign or symptom correlated to leishmaniasis. PMID- 1915790 TI - Short term changes in cardiovascular risk factors in the Di.S.Co. Intervention Project. Research Group of the DI.S.Co. Project. AB - The Di.S.Co. Project--Sezze District Community Control--is aimed at achieving in the general population the prevention of chronic diseases through community intervention. Two areas are enrolled, one for intervention (25,706 subjects) and one for reference (12,655 subjects). In 1983 the first survey was conducted on a sample of males and females aged 20-69, and some risk factors for cardiovascular diseases were measured. In 1986 a second screening was conducted on the same sample examined in 1983 and in a new one to evaluate the effect of community treatment during the three-year intervention. The main net differences obtained in the treatment area against controls (by the paired analysis), adjusted by the initial levels of the risk factors considered, were: in males body mass index: 1.3% and number of cigarettes smoked per day: -5.1%; in females systolic blood pressure: -2.1%, body mass index: -3.2% and number of cigarettes smoked per day: 34.4%. The theoretical probability of death from atherosclerotic cardiovascular diseases in 25 years was estimated by the multiple logistic function and in three years it increased by 1% in males, while for females it decreased by 6.5%. PMID- 1915792 TI - Retention of leptospiral agglutinins and long-term response to administration of monoclonal antibodies in vervet monkeys (Cercopithecus aethiops) on Barbados. AB - In a study of 21 wild-caught Barbadian vervet monkeys (Cercopithecus aethiops sabaeus), naturally-acquired leptospiral agglutinins were found to persist for over five years. Groups of seropositive as well as seronegative vervets were given a placebo, or full-strength monoclonal antibodies MCA F12C3 (Icterohaemorrhagiae copenhageni), or diluted F12C3 MCAs. They were challenged 24 hours later with a suspension of highly virulent leptospires (copenhageni) administered intraperitoneally. Immunoprotection was evident in animals receiving full strength MCAs as measured by their failure to develop any substantial antibody response and by their lower geometric mean titres over a period of 142 weeks (maximum GMT of 113 compared with a maximum of 1280 in the placebo group). Diluted MCAs had little or no protective value. The serological response of the monkeys which were seropositive at capture to challenge with virulent copenhageni antigen was strongly anamnestic both in those given MCAs and those given placebo. None of the naturally or experimentally infected vervets showed clinical signs of leptospiral illness. PMID- 1915793 TI - French intravenous drug users: knowledge and sexual behavior change. AB - In a population based survey conducted in France in 1988, 41 respondents reported present or past intravenous drug use. Controlling for age and gender, intravenous drug users (IDUs) engage in more high risk sexual behavior than the general population (sex with other IDUs, multiple partners), but they do not use condoms more frequently. They are five times more likely to have had an HIV test. PMID- 1915794 TI - Screening of children for enteric bacterial pathogens in the outborn neonatal ward in Lagos, Nigeria. AB - Babies, on admission into a neonatal ward at the Lagos University Teaching Hospital, had their rectal swab specimens examined bacteriologically and screened for enteric bacterial pathogens over a one-year-period at two-week intervals. It was found that on the average there were 3 (9.68%) enteric bacterial pathogens out of an average of 31 admissions at each screening period. The enteric bacterial pathogens isolated included: non-typhoid salmonellae, which accounted for 55 (80.88%) isolates out of the 68 enteric bacterial pathogens, Salmonella typhi 2.94%, Shigella dysenteriae 2.94%, Shigella flexneri 4.41%, S. boydii 1.47%, S. sonnei 1.47%, Campylobacter jejuni 1.47% and Enteropathogenic Escherichia coli (EPEC) 2.94%. The main clinical conditions associated with those babies in whom the enteric pathogens were isolated included sepsis, prematurity, neonatal jaundice and tetanus. It is concluded that the enteric bacterial pathogens, even though they were not directly associated with diarrhoeal disease in the newborns in this study, might have contributed to other illnesses like sepsis and meningitis. It is also noteworthy that the enteric bacterial pathogens isolated sporadically from the babies could have been over-looked in view of the fact that it is not conventional to search for enteric bacterial pathogens in babies without diarrhoea on admission. Rectal swab investigations could provide additional information which might be of epidemiological importance in ill neonates in the clinical settings that prevail in developing countries. PMID- 1915796 TI - New Clostridium difficile serotypes in Poland. AB - Polish isolates of Clostridium difficile strains of different origin were studied. All strains were serotyped according to the Delmee scheme. Twenty-one strains remained untypeable. By typing them with antisera against 5 Polish strains we observed 5 new serotypes. PMID- 1915795 TI - Meningococcal meningitis in Italy: 1887-1986. AB - In Italy three epidemic peaks of meningococcal meningitis have occurred reflecting pandemic recrudescence of the disease. The seasonal distribution of the disease is similar in the epidemic or non-epidemic periods. There is no significant difference in the regional distribution of the disease. The disease is more prevalent among young males. The prevalent serogroup of Neisseria meningitidis is C. There has been a decrease in resistance to sulphonamides and an increase to rifampin among the isolated strains. PMID- 1915797 TI - Possible environmental factors related with transmission of HTLV-I among children. PMID- 1915798 TI - Cell cycle arrest and DNA damage after melphalan treatment of the human myeloma cell line RPMI 8226. AB - Exposure of a myeloma cell line (RPMI 8226) to a 30-minute pulse of melphalan (1 phenylalanine-mustard) resulted in a cell cycle progression delay characteristic for DNA cross-linking agents. Reduction of outflow of cells from late S- and G2 phases was more pronounced as compared to that from G1-phase. The consequence is a progressive accumulation of cells in late S- and G2-phases. At restoration of outflow of cells from late S- and G2-phases, complete removal of DNA interstrand cross-links, as measured by DNA alkaline elution, was noted. At this time less than 50% of maximum DNA-protein cross-links were removed. Further we found no correlation between restored outflow of cells from the G2-phase and removal of DNA-protein cross-links during the follow-up time of 72 h. No DNA double strand breaks as measured by DNA neutral elution were formed during the observation period. The data suggest that removal of DNA interstrand cross-links seems prerequisite for the outflow of cells from G2 after melphalan treatment. PMID- 1915799 TI - A novel monoclonal antibody specific for human pre-B cell leukemia/lymphoma. AB - A novel monoclonal antibody, designated WH14-antibody (WH14-Ab), was produced by using a non-T ALL cell line (HBL-3) as an immunogen. 35S-labelled immunoprecipitate revealed that the antigen reacting with WH14-Ab was estimated to be 30 Kd. Immunoglobulin isotype of WH14-Ab was IgG1. In the normal hematopoietic tissue, WH14-Ab reacted with a small number of monocytes (less than 30%) in the peripheral blood, but neither with the lymphocytes nor granulocytes. WH14-Ab reacted with HBL-3 and REH, but not with other B-cell leukemia/lymphoma and EBV-transformed cell lines. In addition, WH14-Ab reacted with most non-T ALL and pre-B lymphoblastic lymphoma. WH14-Ab did not react with all T-cell lymphomas. These findings indicate that the WH14-Ab may recognize the cell surface determinant shared by immature B cells, especially pre-B cells, in the B cell lineage. WH14-Ab may be useful not only for the detection of pre-B cell leukemia/lymphomas but also for the investigation of maturation and differentiation of B-cell lineage. PMID- 1915801 TI - Peripheral blood T lymphocytes in patients with monoclonal gammopathies: expanded subsets as depicted by capacity to bind to autologous monoclonal immunoglobulins or reactivity with anti-V gene-restricted antibodies. AB - The presence of T cells binding F(ab')2 fragments of the idiotypic immunoglobulin was examined by immunofluorescence in peripheral blood of patients with monoclonal gammopathy. In 3 out of 11 tested patients, 1-15% idiotype-binding T cells of either CD4 or CD8 phenotype were found. In 1 patient both a CD4+ and a CD8+ idiotype-binding T-cell fraction were present. In 1 patient the idiotype binding T cells also reacted with a mAb directed against the variable parts of the TCR alpha or beta chains, further indicating a clonal origin at the alpha/beta level. 3 patients had an expanded predominant T-cell receptor V gene usage based on the reactivity with the limited panel of TCR mAb, but these "clonal" T cells did not bind the idiotype. The study supports the existence of idiotype-specific T cells in peripheral blood of patients with monoclonal gammopathy. Such cells might have a regulatory role on the monoclonal B-cell clone and may be an important target for immunotherapy. PMID- 1915800 TI - Magnetic resonance imaging in idiopathic hemochromatosis. AB - The therapeutic management of patients with idiopathic hemochromatosis (IH) requires an accurate estimate of hepatic iron overload in order to prevent tissue fibrosis and organ failure. Magnetic resonance imaging (MRI) was used to estimate liver iron overload in 5 patients with IH and in 8 normal controls. Signal intensity ratio between liver and subcutaneous fat in T1-, proton- and T2 weighted images was significantly lower in IH when compared with normal controls, and increased gradually during treatment by phlebotomy. Mean serum ferritin at diagnosis was 755 micrograms/l (range: 648-900) in IH and 85 micrograms/l (range: 19-232) in normal controls. A high correlation (r = -0.93) was present between liver signal intensity ratio and serum ferritin; both changed in parallel during removal of iron by phlebotomy. MRI may provide a safe and accurate method of detecting iron overload in the precirrhotic phase of IH, obviating the need for liver biopsy. It may also be used to monitor treatment. PMID- 1915802 TI - Leukocyte removal filtration of platelet concentrates. A study of platelet loss using 111In-labelled platelets and dynamic gamma camera scintigraphy. AB - 111In labelled platelets and gamma camera scintigraphy were used for the study of the platelet loss during leukocyte removal filtration of stored platelets. Two different filters were examined, Imugard IG500 and Pall PL100, and platelet pools containing varying number of platelet concentrates were filtered. It was found that a sizeable amount of the platelets was trapped within the filter. Some of the trapped platelets could be recovered by rinsing the filters with normal saline. The most appropriate rinsing volume to recover lost platelets seemed to match with the "dead space" volume within the filter. It is concluded that radiolabelled platelets and gamma camera scintigraphy appears to be an excellent method to investigate the dynamic events of platelet loss during leukocyte removal filtration. This technique should be well applicable for the study of technological advances in filter construction. PMID- 1915803 TI - Danazol: in vitro effects on human hemopoiesis and in vivo activity in hypoplastic and myelodysplastic disorders. AB - We examined the effects of danazol on in vitro growth of human bone marrow and peripheral blood progenitor cells from 15 normal donors and 5 myelodysplastic patients, and on in vivo hemopoiesis in 30 patients with hypoplastic or myelodysplastic disorders. At concentrations similar to that reported as the plasma level after oral administration, danazol significantly increased CFU-GM colony growth in all normal donors, while the influence on CFU-E, BFU-E, CFU-MK and CFU-GEMM colony growth was less evident. The stimulatory effect on CFU-GM was observed even after accessory cell depletion. Np stimulatory effect either in vitro on the growth of all hemopoietic progenitors or in vivo was observed in 15 myelodysplastic patients, while 7 complete and 3 partial hematological responses occurred in 15 patients with hypoplastic disorders. In conclusion, our results suggest that danazol exerts a direct stimulatory activity in vitro at least on CFU-GM, and a hemopoietic stimulatory effect in vivo in hypoplastic but not in myelodysplastic disorders. PMID- 1915804 TI - Biochemical identification of the antigen recognized by the monoclonal pan-B cell antibody Y29/55. AB - To examine the biochemical structure of the antigen recognized by the monoclonal pan-B cell antibody, Y29/55, the Daudi- and Jurkat-cell lines were labeled by two different methods and immunoprecipitation experiments were carried out. After surface labeling with iodine, two bands with molecular weights of about 38 and 42 kD were observed. The same two proteins were precipitated after biosynthetic labeling with (35S)-methionine from B cells and, to a lesser extent, from T cells. Therefore, it seems that the same proteins, or proteins with similar molecular weight, exist intracellularly in T cells as exist on the surface of, and possibly intracellularly, in B cells. It was confirmed that 80-90% of normal blood-derived B cells were stained with Y29/55 by indirect immunofluorescence. Double-labeling experiments with the pan-B cell antibodies Leu 16 (CD 20) and Leu 12 (CD 19) showed a B-cell population which could be stained with both antibodies (Y29/55 and Leu 16 or Y29/55 and Leu 12). A minor cell population was stained with the antibody Y29/55 alone. Our findings indicate that the antibody Y29/55 recognizes a B-cell antigen, which has not been described previously. PMID- 1915805 TI - Variations in serum erythropoietin and transferrin receptor during phlebotomy therapy of hereditary hemochromatosis: a case report. AB - Serum levels of transferrin receptor and erythropoietin were determined in 2 patients with hereditary hemochromatosis undergoing phlebotomy therapy. The objective of the study was to determine changes in serum transferrin receptor and serum erythropoietin occurring during therapy, and to investigate if such changes could be useful to monitor the therapy. The study showed that serum transferrin receptor, and to a lesser extent serum erythropoietin, may be better parameters than serum ferritin as indicators of when phlebotomy should be discontinued. The most sensitive parameter, however, appeared to be the serum transferrin receptor/ferritin ratio. PMID- 1915806 TI - Immunological properties of ferritin during in vitro maturation of human monocytes. AB - Ferritin in macrophages from human liver and spleen is rich in L subunits but, in the peripheral blood monocytes from which tissue macrophages are derived, the ferritin contains a high proportion of H subunits. We have studied the maturation of monocytes in vitro and the immunological properties of cellular ferritin during this process. Mononuclear cells were isolated from peripheral blood of normal subjects and patients with idiopathic haemochromatosis. Monocytes were obtained by incubation on plastic. The adherent cells were incubated in medium with or without added iron (ferric ammonium citrate) for 20 hours and harvested. Monocytes were also incubated for 7 days before incubation with iron. Ferritin concentrations were determined using immunoassays specific for H and L rich isoferritins. Freshly isolated monocytes were found to have similar concentrations of H- and L-rich isoferritins. Incubation with iron caused an increase in both H- and L-type ferritins. After incubation for 7 d the ferritin present in the normal cell lysates was L-rich and incubation with iron caused accumulation of L-, but not H-type ferritin. Maturation of monocytes is thus associated with the loss of H-rich isoferritins. There were no differences between normal subjects and patients with idiopathic haemochromatosis in ferritin concentrations. In vitro maturation provides an excellent model for studying the developmental control of ferritin synthesis and breakdown. PMID- 1915807 TI - Value of maintenance therapy with chemotherapy or interferon during remission of acute myeloid leukaemia. AB - 108 consecutive patients with de novo acute myeloid leukaemia at ages 15 to 59 years were treated in a prospective controlled multicentre trial. Induction with combination TAD resulted in a complete remission in 85 cases (79%). After a cyclic consolidation programme for 6 months, 73% of the remissions continued. The maintenance therapy was at random either nothing, or alpha interferon, or monthly 5 day courses with thioguanine and cytarabine. The median duration of all remissions was 13 months; that of those in the control and interferon arms 15 months each, and in the chemotherapy arm 18 months. The median survival of all the 108 patients was 16 months; that of those in the control arm 20 months, in the interferon arm 33 months and in the chemotherapy arm 26 months. At 5 yr, 31%, 22% and 31%, respectively, were alive. The survival curves did not differ from each other significantly. Maintenance treatment after an intensive induction and a moderately intensive consolidation was of no benefit in this study. Interferon did not improve the prognosis. PMID- 1915809 TI - Relationship between the proportion of paroxysmal nocturnal hemoglobinuria (PNH) III-erythrocytes and the frequency of exacerbated hemoglobinuria in PNH. PMID- 1915808 TI - Patients treated with natural (leukocyte-derived) interferon (IFN)-alpha do not develop IFN antibodies. PMID- 1915810 TI - [The effect of lithium oxybutyrate on the circadian rhythms of the activity and body temperature of rats maintained under different light regimens]. AB - The chronobiological properties of lithium hydroxybutrate were studied in the open field test at the preventive administration of the drug to rats (7 days, 10 mg/kg daily subcutaneously) kept under natural photoperiod of the summer and winter solstice and CT 12:12. It was found that lithium hydroxybutrate can preserve, reveal the lost rhythms and synchronize the available circadian and infradian rhythms of the activity and body temperature of the rats. The degree and direction of this effect depend on the initial rhythmostasis, the time of the drug administration and the regimen of illumination under which the animals are kept. PMID- 1915811 TI - [The analgetic activity of antidepressants and their influence on the pain relieving effect of acupuncture]. AB - The analgesic properties of new Soviet-made antidepressants pyrasidol, incazan, tetrindol as compared with amitriptyline and their influence on the analgesic effect of acupuncture were studied in experiments on rats by using the method of electrical stimulation of the tail root with stimuli of the increasing intensity. All the studied drugs at single and subchronic (6 days) administration possessed the analgesic actions. Pyrasidol exerted the most pronounced effect. The antidepressants enhanced the analgesic effect of electroacupuncture, in particular during activation of the points of general action and this effect showed up to the greatest degree under medication with pyrasidol. PMID- 1915812 TI - [Experimental and clinical data on the characteristics of analgesic action during forced immobilization]. PMID- 1915813 TI - [The action of amtizol and gutimin on the respiratory metabolism of the neuron]. AB - The effects of antihypoxants gutimine and amtisole on oxygen consumption by the intact nerve cell of the invertebrate and the activity of NADN-DH and SDH dependent ways of oxidation in the cell were studied. Under normoxia gutimine inhibited the nerve cell respiration and decreased the activity of NADN-DN and SDH-dependent ways of oxidation by 15% and 5% respectively. Amtisole activated the neuron respiration increasing the activity of NADN-DH-dependent way of oxidation. Both antihypoxants, despite the fact that they refer to the same class of compounds, have different mechanisms of action on the neuron metabolism. Gutimine appears to be a pharmacological agent, protector, amtisole as an initiator of the active adaptative reorganization of the intracellular metabolism. PMID- 1915814 TI - [The protective action of vasocyclin (prostacyclin) on the ischemic myocardium]. AB - The effect of vasocyclin (prostacyclin) on the blood supply, activity and functional state of the intact and ischemic myocardium was studied in experiments on anesthetized cats. The drug (100, 300 and 500 mg/kg/min) was shown to produce a dose-dependent increase of the coronary blood flow, systolic and cardiac outputs, an enhancement of the myocardial contractile function, a lowering of arterial blood pressure. Under acute occlusion of the coronary artery vasocyclin improves the functional state of the myocardial ischemic focus, stabilizes the contractile and pumping functions of the heart, exerts the antiarrhythmic action. PMID- 1915815 TI - [The absence of a parallelism between the antihypoxic and anti-ischemic actions of pharmacological agents]. AB - The experiments on different species of animals (mice, cats) showed the lack of parallelism between the antihypoxic and anti-ischemic effects of pharmacological agents. Of four studied antihypoxic agents (lithium oxybutyrate, piracetam, glyo 6, a derivative of pyrimidine S-207) only GABA derivatives showed an increase of the lactate/pyruvate ratio in the blood of the venous sinus under occlusion of the coronary artery and consequently possessed the anti-ischemic properties. Such difference in the effects of the antihypoxic agents on the myocardium was determined to a certain degree by their different influences on the collateral coronary blood circulation. PMID- 1915816 TI - [The anti-arrhythmic activity of the arylamides of alpha hexamethyleneiminocarboxylic acids]. AB - A high antiarrhythmic activity of arylamides of alpha-hexamethyleniminocarbonic acids was found on different experimental models of arrhythmias. It was shown that the lengthening of the carbonic chain in carbonic acids (R) as well as the change from ortho-toluidides to xylidides or mesidides in the aromatic fragment of the molecule increased the antiarrhythmic activity of the studied compounds, their toxicity also increased. The choice of compounds with optimal properties is determined by the combination of all investigated factors: intensity and duration and also the specific features of the spectrum of the antiarrhythmic effect, toxicity and therapeutic range. PMID- 1915817 TI - [The angioprotector and hypolipemic activity of leukomizin in experimental atherosclerosis]. AB - A sesquiterpenic lactone leucomyzin possessing the anti-inflammatory activity significantly reduces the extensiveness of atherosclerotic lesions of the aortas of the rabbits receiving dietary cholesterol. The drug prevents an increase of permeability of the aorta and microvessels under the influence of cholesterol, bradykinin, ovalbumin and histamine. In addition to the angioprotective action, leucomyzin possesses the hypolipidemic activity in rats with experimental hyperlipidemias and (after prolonged administration) in rabbits with cholesterol atherosclerosis. By its antiatherosclerotic and angioprotective activity leucomyzin is superior to prodectine, by its hypolipidemic action it is comparable with miscleron. PMID- 1915818 TI - [The protective properties of monoamines and amino acids in an indomethacin induced stomach lesion in rats]. AB - Serotonin, histamine, tryptophan administered in low doses were shown to protect the rat gastric mucosa against indomethacin-induced hemorrhages. When administered in high doses, serotonin retained the protective properties, while histamine and histidine, on the contrary, increased the hemorrhagic lesion of the tissue. Tryptophan and histidine given in low doses promoted a decrease of the indomethacin elevated levels of serotonin and histamine in the gastric mucosa. PMID- 1915819 TI - [The effect of metacin on the activity of digestive enzymes participating in the hydrolysis of fats normally and in stress]. AB - The effect of a peripheral cholinolytic methacin on the activity of lipolytic enzymes of the pancreas and small intestine was studied on intact and stress exposed animals. The drug was shown to induce certain changes in the activity of lipolytic enzymes. The preliminary administration of methacin attenuates the shifts in the activity of the studied enzymes observed under stress action. PMID- 1915820 TI - [The effects of cholinergic preparations in Alzheimer's disease]. PMID- 1915822 TI - [Structural phospholipids and the lipid peroxidation processes after the action of a platinum preparation]. AB - In the initial period after a single toxic administration of cis dichlordihydrooxyamine platinum in the rat liver there was found an increase of the contents of total phospholipids (PL) at the expense of the change in the contents of lysofractions as well as phosphatidylcholine (PC), polyglycerophosphates (PGP) and phosphatide acids. There was observed suppression of the antiradical activity leading to intensification of lipid peroxidation (LPO) processes. In the later periods of the experiment the decrease of phospholipid contents is determined by a reduction of the levels of phosphoinosites, sphyngomyelin, PGP. At the same time the processes directed at the restoration begin to function resulting in normalization of some links of LPO and the PL fractions which are the most important during reparation of hepatocytic membranes. PMID- 1915823 TI - [The inhibiting effect of cimetidine on a number of enzymes]. AB - The results of the comparative study on the contents and activity of the enzymes of the system of oxidases of mixed function in the lungs and liver in rabbits, the specific features of phospholipid spectrum in the supernatant and microsomal fractions of the lungs and liver tissues are presented. The same parameters were investigated in experimental chronic inflammatory diseases of the lungs. The degree of the damage of the monoxygenase capacity of the lungs and the degree of the liver involvement in the process were established. The peculiarities of the inhibitory action of cimetidine on the detoxication capacity of the lungs and liver and on the disorder of the reproduction of phospholipids in these organs were revealed. The substrate specificity of cimetidine in inhibition of microsomal NADPN-cytochrome-C-reductase both in the liver and in the lungs, the probability of blocking the synthesis of phospholipids at the level of phosphatide acid and citidinephosphatecholine were noted. The results obtained should be taken into consideration during drug therapy. PMID- 1915821 TI - [The contraceptive efficacy and mechanism of action of combinations of ethinyl estradiol and norethisterone acetate]. AB - The purpose of the study was to establish the optimal combinations of ethynilestradiol and norethysterone acetate exhibiting a high contraceptive activity. It was shown that the ratio of 1:20 (ethynilestradiol 0.04 mg/kg and norethysterone acetate 0.8 mg/kg) is characterized by a high contraceptive efficacy. The inhibitory effect on the incretion of lutropin and follitropin leading to the change of the process of oogenesis and gravidary reorganization of the endometrium underlies probably the mechanism of action. PMID- 1915824 TI - [The carcinogenic activity of spirobromine]. AB - The carcinogenic activity of spyrobromin was studied during the chronic experiment on 1.5-2-month-old rats and mice of both sexes. The drug was administered intragastrically and intraperitoneally once a week in the maximally tolerant dose for 24 months. Under the given experimental conditions spyrobromin can diminish the latent period of the development of tumours in the experimental rats at intraperitoneal administration. At intragastric administration of the drug no decrease was noted in the latent period and no increase of tumours was observed in the experimental groups of the animals as compared with control. Spyrobromin is considered to be a weak carcinogen. The oral route of administration is the most safe with respect to the oncogenic risk. PMID- 1915825 TI - [New drug forms of isosorbide dinitrate: the problem of an objective evaluation in patients with ischemic heart disease]. AB - In 7 patients with ischemic heart disease and stable angina pectoris the efficacy of three oral isosorbide dinitrate (ID) formulations, nitrosorbide, isodinite and isodinite-retard, was compared. The antianginal and anti-ischemic effects were assessed in terms of exercise treadmill tests performed prior to and repeatedly after (2, 5 and 7 hours) single-dose administration (in comparison with placebo). The efficacy of isodinite-retard only slightly differed from that of placebo. Isodinite had a more pronounced effect than nitrosorbide, although the duration of isodinite effect was shorter than that of nitrosorbide. Plasma ID and its metabolite, isosorbide-5-mononitrate concentrations mirrored exercise duration changes. ID content in the tablets of all formulations studied corresponded to those indicated by the manufacturer. The differences in the efficacy of ID formulations can be attributed to the differences in their bioavailability. Thus, the method used permitted to reveal significant distinctions in the efficacy of different ID formulations. These distinctions must be taken into account in clinical practice. PMID- 1915826 TI - [The effect of trofopar, AICA phosphate and Essentiale on the detoxifying function and blood circulation of the liver in lesions in man]. AB - The comparative clinicopharmacological studies established the ability of hepatotropic agents with the membrane stabilizing properties and metabolic activity--trophopar, aika-phosphate and essential to stimulate to various degrees the processes of microsomal oxidation of antipyrine in hepatocytes at their insufficiency in patients with lesions of the hepatobiliary system of the alcohol and viral etiology. The studied drugs improve also the condition of the intrahepatic hemodynamics according to the findings of rheohepatography. The correlations between the positive dynamics of the values of antipyrine clearance, the degree of arterial blood filling (the rheographic index) and the increase of serum albumin content were found that confirms the ability of trophopar, aika phosphate and essential to exert the complex influence on the systems and mechanisms of the realization of the liver antitoxic function. PMID- 1915827 TI - [Radiospectroscopic research on the interaction of the pyrazole molecule with phospholipids]. AB - By using the NMR spectroscopy it was shown that hydrogen bond is formed during the interaction between pyrazole molecule and iecithin. The hydrogen bond formation is probably one of the manifestations of the biological activity of pyrazole. PMID- 1915828 TI - [A chronobiological approach to evaluating the individual reactivity of animals in a practical psychopharmacological experiment]. AB - As shown numerous data from our laboratory in time course of different behavioral tests (active avoidance response, re-learning in Y-maze etc.) and psychopharmacological effects (amphetamine-induced stereotypy, haloperidol catalepsy) short period (minute or second range) fluctuations are presented. By means of their account rhythmical patterns may be obtained individually for each animals. On this basis all animals can be typified such that can serve as a safe prognostic criterion of individual pharmacological sensitivity and speed of development of development of tolerance to psychotropic drugs. PMID- 1915829 TI - [The unreliability of selecting short- and long-sleep mice by the results of a one-time determination of the duration of ethanol anesthesia]. AB - Duration of ethanol (5 g/kg, orally) anesthesia was measured in male C57 B1/6 and white SHR (bred from Swiss) mice in three consecutive experiments with a 7-day interval between them. The number of short-sleep (SS) mice (duration of anesthesia was 30 min) and long-sleep (LS) mice (duration of anesthesia was over 120 min) in the selected groups decreased in the second and third experiments. This means that groups of SS and LS taken one and two weeks after the first selection for any experiment are not homogeneous because only in some animals the initial characteristics remain. PMID- 1915830 TI - [The determination of ampicillin in the blood and urine of patients by microcolumn high-performance liquid chromatography]. AB - The method of the quantitative determination of ampicillin in the blood serum and urine on the Soviet-made chromatograph "Milichrom" with an ultraviolet detector and 2 x 62 cm column is described. The conditions of chromatography were as follows: wavelength-210 nm; elution rate-100 microliters/min; analysis time-12 min. The conditions of chromatographic analysis were selected on sorbents Lichrosorb RP-18, Nucleosil S-18 and Silosorb S-18. The given method of ampicillin determination--is characterized by a high specificity, accuracy, the use of small volumes of the blood taken from a finger, the rapidity of making analyses and may be recommended for introduction in the clinical practice for optimization of treating patients with ampicillin. PMID- 1915831 TI - [The use of the perfused rat heart as a model for selecting antihypoxic compounds]. AB - The test system for selection of antihypoxic compounds was developed and approved on the basis of the model of the perfused rat heart. It was found that the hypoxic state of the moderate degree of severity simulated on the myocardium is optimal for the assessment of the studied antihypoxic compounds. Taking into consideration the fact that at the early stages of hypoxia the electron transport is disordered at the level of the first enzymatic complex of the respiration chain, the protective actions of the agents (menadione and hydroquinone) being able of shunting the respiration chain to bypass the damaged area were studied. It was found that under hypoxia these compounds improve the energy-dependent contractile properties of the myocardium, that is, show up the antihypoxic effects. PMID- 1915832 TI - [Buspirone as a representative of a new generation of tranquilizers-anxiolytic agents]. PMID- 1915833 TI - [The clinical use of the preparation kordaron in different arrhythmias]. AB - Cordaron (amiodaron, angoron, atlansil, cordinil, trangorax) is a drug produced by the French-Belgian firm "Labaz". Some pharmacological properties of cordaron and in particular its ability to increase the refractory period both of the atrioventricular junction and the abnormal pathway that hampers the circulation of excitation between the atria and ventricles influencing the mechanism of reverse excitation provide favourable conditions for elimination of arrhythmias. In a number of papers of the Soviet and foreign authors there are presented the results of cordaron treatment of patients with various cardiac rhythm disorders which indicate a fairly high antiarrhythmic effectiveness of the drug. Its lethal dose is practically absent. Side effects show up only during a prolonged therapy and disappear after the drug withdrawal. PMID- 1915834 TI - Treatment of intact hepatocytes with synthetic diacyl glycerols mimics the ability of glucagon to cause the desensitization of adenylate cyclase. AB - Incubation of intact hepatocytes with either of the synthetic diacyl glycerols 1 oleoyl-2-acetyl glycerol (OAG) or dihexanoyl glycerol (DHG) caused the transient uncoupling of the ability of glucagon to stimulate adenylate cyclase in membranes prepared from those cells. No change occurred in either the activity of the catalytic unit of adenylate cyclase or the coupling of Gs to adenylate cyclase. Diacyl glycerol action appeared to mimic glucagon-mediated desensitization of adenylate cyclase, suggesting that protein kinase C activation may provide the molecular trigger for glucagon desensitization. PMID- 1915836 TI - Biosynthesis of paf-acether. XVII. Regulation by the CoA-independent transacylase in human neutrophils. AB - Treatment of intact human polymorphonuclear neutrophils (PMN) with low concentrations of phorbol myristate acetate (PMA, 1-10 ng/ml) induced paf-acether (paf) and lyso paf formation, arachidonate release, and simultaneous inhibition of CoA-independent lyso paf: transacylase as assayed in a cell-free system. Inhibition of [3H]lyso paf reacylation was also observed when it was exogenously added to the PMA-treated intact PMN. When higher concentrations of PMA (40-100 ng/ml) were used, paf biosynthesis was severely impaired and the level of the CoA independent transacylase activity returned to basal level. Since lyso paf appears to be the substrate for PMA-activated paf formation (remodeling pathway), we showed that [14C]acetate was incorporated into the paf molecule. By contrast, labeling with [3H]choline was not appropriate in this model. The presented results are against the involvement of a de novo route in paf synthesis initiated by PMA and open a new possibility of an important role for the CoA-independent transacylase in controlling the level of lyso paf availability for paf formation. PMID- 1915835 TI - cDNA sequence of a Drosophila melanogaster gene, Dfur1, encoding a protein structurally related to the subtilisin-like proprotein processing enzyme furin. AB - Screening a genomic library of Drosophila melanogaster DNA with a human fur cDNA probe resulted in the isolation of DNA clones that apparently belonged to two different DNA regions of the Drosophila genome. Subsequently, corresponding Drosophila cDNA clones were isolated. Nucleotide sequence analysis indicated that these cDNA clones originated from two different genes, which were called Dfur1 and Dfur2. From overlapping Dfur1 cDNA clones, a composite cDNA could be constructed and analysis of its nucleotide sequence revealed the coding sequence for a protein of 899 amino acid residues. This protein, designated Dfurin1, exhibited striking sequence homology to human furin and contained the same protein domains except for the cysteine-rich region. Furthermore, unlike human furin, Dfurin1 possessed an extended amino-terminal region in which a potential transmembrane anchor was present. PMID- 1915837 TI - Introduction of BAPTA into intact rat submandibular acini inhibits mucin secretion in response to cholinergic and beta-adrenergic agonists. AB - Incorporation of the calcium chelator BAPTA into isolated, intact rat submandibular acini by hypotonic swelling, resulted in complete inhibition of carbamylcholine, noradrenaline and isoproterenol stimulation of mucin secretion. No effects of intracellular BAPTA on cell viability or beta-adrenergic stimulation of cyclic AMP formation were observed. The data are the first to demonstrate that calcium is necessary for beta-adrenergic stimulation of secretion and suggest that Ca2+ provides a common link in the triggering of exocytosis. PMID- 1915838 TI - Cell adhesive activity of two animal lectins through different recognition mechanisms. AB - Cell adhesive activity of two animal lectins, frog (Rana catesbeiana) S-type 14K lectin and echinoidin (a C-type lectin from sea urchin plasma), was studied with human rhabdomyosarcoma (RD) cells. RD cells attached to and spread on plastic plates coated with each lectin. Cell adhesion by the frog lectin was completely inhibited by the addition of lactose or asialofetuin glycopeptide. Echinoidin induced cell adhesion was only inhibited by peptide GRGDS. Since echinoidin is known to contain an RGD-sequence, our results clearly indicate that this sequence is active as the cell adhesive signal. These results suggest that some of the animal lectins may function as a cell adhesive molecule rather than using the carbohydrate-recognition mechanism. PMID- 1915839 TI - Modification of alpha-amylase from Bacillus licheniformis by the polyaldehyde derived from beta-cyclodextrine and alpha-amylase thermostability. AB - The cleavage of beta-cyclodextrine by sodium periodate at the seven 2-3 diols of the glucose unit gives rise to the polyaldehyde 1, used to modify alpha-amylase. The reductive modification of alpha-amylase from Bacillus licheniformis reduced the number of reactive lysine groups from 8 to 3.5 per mol of enzyme with an activity loss of 25% and increased the half-life at 80 degrees C from 4.7 to 7.0 minutes. PMID- 1915840 TI - A distinct 2,5-di-(tert-butyl)-1,4-benzohydroquinone-sensitive calcium store in bovine adrenal chromaffin cells. AB - The fluorescent Ca2+ indicator Fura 2 was used to monitor Ca2+ release induced by the Ins(1,4,5)P3-mobilizing agonist angiotensin II (Ag II), caffeine and 2,5-di (tert-butyl)-1,4-benzohydroquinone (tuBHQ), in intact bovine adrenal chromaffin cells. Under low external Ca2+ conditions, tuBHQ, Ag II and caffeine elicited Ca2+ rises, indicating Ca2+ release from internal stores. Prior addition of Ag II had no noticeable effect on the extent of release of Ca2+ induced by tuBHQ. Stimulation of the cells with tuBHQ before either Ag II or caffeine, similarly had no effect on Ca2+ released by these two agonists. It was concluded, therefore, that there is a third intracellular Ca2+ store in bovine adrenal chromaffin cells, distinct and non-overlapping, from those sensitive to caffeine or Ins(1,4,5)P3-mobilizing agonists. PMID- 1915841 TI - Characterization of a tissue-type plasminogen activator from porcine urine. AB - Porcine urine, unlike human urine, does not contain detectable amounts of urokinase-type plasminogen activator (u-PA). The plasminogen activator present in porcine urine is of tissue-type (t-PA) as identified by the following criteria. (1) Porcine urine PA exhibits an Mr of 65,000 similar to the Mr of human t-PA (64 70,000) but distinct from the Mr of human u-PA (55,000). (2) Antibodies against human t-PA bind and inhibit crude and purified porcine urine PA, while human u-PA specific antibodies do not react with porcine urine PA. (3) Plasminogen activation by porcine urine PA is markedly stimulated in the presence of fibrinogen fragments. (4) Porcine urine PA activity is not affected by concentration of amiloride substantially suppressing human u-PA activity. PMID- 1915842 TI - ADP/ATP translocator is essential only for anaerobic growth of yeast Saccharomyces cerevisiae. AB - All three genes (AAC1, AAC2 and AAC3) encoding the mitochondrial ADP/ATP translocator, were inactivated in a haploid yeast strain by a gene disruption technique. The triple mutant was still able to grow on fermentable carbon sources but only in the presence of oxygen. Under aerobic conditions neither translocator protein nor carrier-mediated transport was detected in all mutants in which the AAC2 gene was disrupted. It was further shown that a functional AAC genes product is essential only for anaerobic growth of Saccharomyces cerevisiae but not for growth under derepressed conditions. Under anaerobic conditions a non-detectable amount of AAC3 gene product is sufficient to ensure the cell growth and multiplication. PMID- 1915843 TI - The induction of lamellar stacking by cholesterol in lecithin-bile salt model systems and human bile studied by synchrotron X-radiation. AB - Small angle X-ray scattering (SAXS) with synchroton radiation was used to investigate interactions among lipid particles in lecithin-bile salt model systems and in native gallbladder biles. In model systems in the absence of cholesterol, isotropic, continuous spectra were found, indicating the absence of periodic structures. In the presence of excess cholesterol, interaction in the form of lamellar stacking was detected by the appearance of discrete diffraction peaks. In the supersaturated cholesterol region of the commonly accepted phase diagram [1], where cholesterol crystals were expected, we found lamellar stacking. The high proportion of cholesterol to bile salts seems to be the common denominator of these models. The lamellar stacking was also found in native unprocessed bile. This effect of cholesterol on lipid structure has not been previously described. Lamellar stacking may contribute to cholesterol solubilization. Its influence on the kinetics of cholesterol crystallization is presently unknown. PMID- 1915845 TI - Distribution of a negative regulator of haematopoietic stem cell proliferation (AcSDKP) and thymosin beta 4 in mouse tissues. AB - A competitive enzyme immunoassay using acetylcholinesterase as tracer for thymosin beta 4, has been developed. Using this assay and a previously described EIA for AcSDKP, a negative regulator of pluripotent haematopoietic stem cell proliferation, the levels of these two peptides were determined in mouse tissue extracts. The combination of EIAs with different HPLC procedures validated these methods and clearly demonstrated the ubiquity of these peptides in mouse tissues. Similar results are reported for rabbit thymus which suggest different hypotheses for AcSDKP biosynthesis. PMID- 1915844 TI - Involvement of sapecin in embryonic cell proliferation of Sarcophaga peregrina (flesh fly). AB - Addition of antibodies against sapecin to the culture medium of NIH-Sape-4 cells derived from a Sarcophaga embryo greatly inhibited cell proliferation, whereas addition of sapecin stimulated cell proliferation. These results suggest that sapecin is involved in the proliferation of embryonic cells of Sarcophaga. Sapecin is known to have potent antibacterial activity, so it seems to have two different biological functions: i.e. protection against bacterial infection and stimulation of embryonic cell proliferation. PMID- 1915846 TI - Functioning of quinone acceptors in the reaction center of the green photosynthetic bacterium Chloroflexus aurantiacus. AB - The photosynthetic reaction centers (RC) of the green bacterium Chloroflexus aurantiacus have been investigated by spectral and electrometrical methods. In these reaction centers, the secondary quinone was found to be reconstituted by the addition of ubiquinone-10. The equilibrium constant of electron transfer between primary (QA) and secondary (QB) quinones was much higher than that in RC of purple bacteria. The QB binding to the protein decreased under alkalinization with apparent pK 8.8. The single flash-induced electric responses were about 200 mV. An additional electrogenic phase due to the QB protonation was observed after the second flash in the presence of exogenous electron donors. The magnitude of this phase was 18% of that related to the primary dipole (P+QA-) formation. Since the C. aurantiacus RC lacks H-subunit, this subunit was not an obligatory component for electrogenic QB protonation. PMID- 1915847 TI - The protecting effect of L-carnitine on Ca(2+)-loaded rat liver mitochondria. AB - It is shown that L-carnitine strongly increases the ability of rat liver mitochondria to respond to the train of Ca2+ additions by a transient stimulation of the State-4 respiration rate. Such an effect requires ATP and the L-carnitine efficiency strongly decreases when ATP is omitted. Oleate influences the mitochondria in a fashion opposite to that of L-carnitine. The oleate effect is strongly diminished by L-carnitine. Again, the L-carnitine effect requires ATP, and D-carnitine fails to substitute for L-carnitine. It is suggested that L carnitine removes, in an ATP-dependent manner, endogenous or added fatty acids, which are involved in oxidative damage of Ca(2+)-loaded mitochondria. PMID- 1915848 TI - Electron microscopy of the complexes of ribulose-1,5-bisphosphate carboxylase (Rubisco) and Rubisco subunit-binding protein from pea leaves. AB - The structure of ribulose-1,5-bisphosphate carboxylase (Rubisco) subunit-binding protein and its interaction with pea leaf chloroplast Rubisco were studied by electron microscopy and image analysis. Electron-microscopic evidence for the association of Rubisco subunit-binding protein, consisting of 14 subunits arranged with 72 point group symmetry, and oligomeric (L8S8) Rubisco was obtained. PMID- 1915849 TI - Identification of the site phosphorylated by casein kinase II in smooth muscle caldesmon. AB - Phosphorylation of avian gizzard caldesmon by casein kinase II was investigated. The enzyme incorporates about 1 mol of phosphate per mol of caldesmon. All sites of phosphorylation are located in short chymotryptic peptides with Mr 25-27 kDa or in the short N-terminal peptide formed after cleavage of chicken gizzard caldesmon at Cys153. The primary structure of the tryptic peptide containing the main site of duck gizzard caldesmon phosphorylation is S-E-V-N-A-Q-N-X-V-A-E-D-E T-K, where X is an unidentified residue, presumed to be phosphoserine. Thus, Ser73 is the main site phosphorylated by casein kinase II in avian gizzard caldesmon. PMID- 1915850 TI - Identification of potential amino acid residues supporting anticodon recognition in yeast methionyl-tRNA synthetase. AB - Sequence comparisons among methionyl-tRNA synthetases from different organisms reveal only one block of homology beyond the last beta strand of the mononucleotide fold. We have introduced a series of semi-conservative amino acid replacements in the conserved motif of yeast methionyl-tRNA synthetase. The results indicate that replacements of two polar residues (Asn584 and Arg588) affected specifically the aminoacylation reaction. The location of these residues in the tertiary structure of the enzyme is compatible with a direct interaction of the amino acid side-chains with the tRNA anticodon. PMID- 1915851 TI - 15N NMR studies of the conformation of E. coli dihydrofolate reductase in complex with folate or methotrexate. AB - We have employed 15N NMR to characterize the conformations of Escherichia coli dihydrofolate reductase (ECDHFR) in complex with [5-15N]folate or [5 15N]methotrexate (MTX). Two 15N resonances were observed for DHFR/MTX binary complex. The relative population of these two conformations is pH dependent. Addition of NADP+ or NADPH results in the disappearance of the low field resonance. In contrast, only one conformation was observed for both the DHFR/folate and DHFR/folate/NADP+ complexes. However, the 15N chemical shift of [5-15N]folate in the binary DHFR/folate complex is 7.28 ppm upfield from that of the ternary complex, suggesting the possible loss of a hydrogen bonding to N5 of folate in the ternary complex. PMID- 1915852 TI - Identification of seven novel protein-tyrosine kinase genes of Drosophila by the polymerase chain reaction. AB - We used the polymerase chain reaction to identify 7 novel tyrosine-kinase genes (dtk1 to -7) in Drosophila melanogaster, dtk4 coded for a part of the kinase catalytic domain nearly identical in sequence to that of the human receptor for insulin-like growth factor 1, whereas sequences encoded by dtk1 and dtk2 were highly homologous to that of the chicken fibroblast growth factor receptor. PMID- 1915853 TI - Platelet-activating factor activates cardiac GK via arachidonic acid metabolites. AB - Platelet-activating factor (PAF), added to the bathing solution, stimulated the cardiac muscarinic K+ channel (KACh) in the cell-attached patch (no agonist in the pipette). The PAF-induced KACh channel activation was blocked by WEB2086, a PAF-receptor inhibitor, indicating that the PAF-receptor mediated the response. PAF-induced activation was prevented by nordihydroguaieretic acid, a lipoxygenase inhibitor, and AA-861, a 5-lipoxygenase inhibitor, but was not affected by indomethacin, a cyclo-oxygenase inhibitor. The PAF-induced KACh channel activity disappeared upon formation of inside-out patch. In this inside-out patch, intracellular GTP alone induced maximal channel reactivation, which was inhibited by GDP-beta S. These results suggest that 5-lipoxygenase metabolites of PAF released arachidonic acid cause a persistent stimulation of GK but not the KACh channel itself, resulting in a receptor-independent activation of the KACh channel by GTP. PMID- 1915854 TI - Different superstructural features of the light responsive elements of the pea genes rbcS-3A and rbcS-3.6. AB - Analyses of the DNA sequences, named Light Responsive Elements (LREs), relevant in the photoactivation of the two pea genes rbcS-3A and rbcS-3.6, encoding the same protein but differently expressed, have been carried out, taking advantage of two complementary methods; a theoretical analysis, based on conformational energy calculations, and an experimental evaluation of LREs curvature, derived from gel electrophoretic mobilities of multimers of the LREs and of oligonucleotides corresponding to the three boxes in which they can be dissected. Theoretical and experimental analyses show that the curvature of the rbcS-3A LRE is larger than that of rbcS-3.6 LRE, and seems to be correlated with rbcS-3A higher transcription efficiency. PMID- 1915855 TI - 2D 1H NMR studies of oxidized 2(Fe4S4) ferredoxin from Clostridium pasteurianum. AB - Oxidized ferredoxin from Clostridium pasteurianum, containing two Fe4S4 clusters, has been investigated using 2D 1H NMR spectroscopy at 600 MHz. 2D NMR experiments allowed complete assignment of the sixteen isotropically shifted signals corresponding to the beta-CH2 protons of the eight metal coordinated cysteines. Geminal connectivities of Cys beta-CH2 protons were identified through magnitude COSY experiments and confirmed through 2D NOESY experiments. A few additional signals could be assigned to the corresponding alpha-CH protons. The importance of 2D experiments to achieve firm assignments of isotropically shifted signals in paramagnetic metalloproteins is stressed. PMID- 1915856 TI - Molecular cloning and nucleotide sequence analysis of a cDNA encoding pea cytosolic ascorbate peroxidase. AB - A cDNA clone encoding the cytosolic ascorbate peroxidase of pea (Pisum sativum L.) was isolated and its nucleotide sequence determined. While ascorbate peroxidase shares limited overall homology with other peroxidases, significant homology with all known peroxidases was found in the vicinity of the putative active site. PMID- 1915857 TI - Characterization of full-length cDNAs and the gene coding for the human GM2 activator protein. AB - Full-length cDNAs coding for the human GM2-activator protein has been isolated and characterized, and its genomic structure studied in two overlapping clones in lambda-EMBL-4 isolated from a human brain genomic library. Two different cDNAs were found that were identical to the 5'-terminus to nt 1311 (counted from the A of the initiation codon, ATG) including the entire protein coding sequence. However, they were entirely dissimilar in the 3'-non-coding sequences. The genomic clones covered 94% of the full-length cDNA sequence. Three introns were found. The last exon spans contiguously the carboxyl terminus of the protein and the entire 3'-untranslated region of one of the two cDNAs with different 3'-ends. The origin of the 3'-portion of the other cDNA clone is not clear at this time. PMID- 1915858 TI - A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB. AB - GM2-gangliosidoses are neurological disorders caused by a genetic deficiency of either the beta-hexosaminidase A or the GM2 activator, a glycolipid binding protein. In a patient with an immunologically proven GM2 activator protein deficiency, A T412----C transition (counted from A of the initiation codon) was found in the coding sequence, which results in the substitution of Arg for the normal Cys107 in the mature GM2 activator protein. The remainder of the coding sequence remained entirely normal. PMID- 1915859 TI - A metallothionein-like gene from maize (Zea mays). Cloning and characterization. AB - A differentially expressed maize gene has been cloned and sequenced. Transcriptional and translational start sites have been mapped and 2.5 kb of 5' flanking DNA were sequenced. The 8 kDa protein encoded by this gene shows striking similarity to the metallothionein-like proteins recently described in Pisum sativum and Mimulus guttatus. The maize MT-L gene message is very abundant in roots without exposure to high levels of metals, present at lower concentration in leaves and pith, and at very low concentration in seed. PMID- 1915860 TI - Binding sites in fibronectin for an enterotoxigenic strain of E. coli B342289c. AB - The binding of fibronectin and fibronectin fragments to the enterotoxigenic strain E. coli B34289c was studied. E. coli cells bound to two distinct sites of fibronectin, one being the N-terminal domain, which also contains the binding sites for staphylococci and streptococci, and the other located within the central heparin binding region. In addition, the N-terminal and the heparin binding domain mediated the attachment of bacteria in a solid phase binding assay. E. coli cells expressed two classes of receptors, the first, a 17 kDa protein, recognized by the N-terminal fragment and the second, having a mol. mass of 55 kDa, which interacts with the internal heparin binding domain. Bacterial receptors, which bind the N-terminal end of fibronectin, may be structurally related. PMID- 1915861 TI - Immunological demonstration of epsilon PKC. Murine tissue distribution, ontogeny, cellular localization and translocation. AB - An antiserum raised against an epsilon PKC-specific peptide recognizes epsilon PKC with an apparent molecular weight of 97 kDa in cytosol of mouse brain. No cross-reaction with alpha, beta, gamma PKC or the delta PKC-like p76-kinase is observed. Epsilon PKC is mainly present in brain. Just traces of this PKC isoenzyme can be detected in some other murine tissues. Ontogenetic studies indicate that the amount of epsilon PKC in murine brain increases constantly and reaches a maximal level at day 7 after birth. Upon TPA activation epsilon PKC is translocated from the cytosol to the particulate fraction in a brain homogenate. PMID- 1915862 TI - Proton NMR investigation of the reconstitution of equine myoglobin with hemin dicyanide. Evidence for late formation of the proximal His93F8-iron bond. AB - Reconstitution of apoequine myoglobin (apoEqMb) with hemin dicyanide (FePPIX(CN)2) was monitored by 1H NMR spectroscopy to gain information about the sequence of events leading to metEqMbCN. At least one step in the pathway is slow enough to allow us to follow the time-dependence of formation of the product, a mixture of heme-insertion isomers characterized by others (Jue, T., Krishnamoorthi, R. and La Mar, G.N. (1983) J. Am. Chem. Soc. 105, 5701-5703; Lecomte, J.T.J., Johnson, R.D. and La Mar, G.N. (1985) Biochim. Biophys. Acta 829, 268-274). However, in contrast to all previously reported Mb-FePPIX reconstitutions, we find that the initial ratio of heme-insertion isomers is not 1:1. This mixture is, instead, found to be enhanced in the isomer which dominates at equilibrium. This is taken as evidence for a '[FePPIX(CN)2.EqMb]' intermediate which lacks the proximal His93F8-Fe bond and which proceeds quickly toward an equilibrium ratio of heme-insertion isomers. Therefore the heme-insertion isomer ratio is frozen only when the proximal His93F8-Fe bond is formed. The difference in this ratio of heme-insertion isomers between EqMb (4.5:1) and SwMb (2.5:1) likely reflects the amino acid substitution: Lys----Arg45CD3 (EqMb----SwMb). PMID- 1915863 TI - Hydrolysis of branched cyclodextrins by a cyclodextrin-hydrolyzing enzyme from Bacillus sphaericus E-244. AB - The action of a cyclodextrin-hydrolyzing enzyme from Bacillus sphaericus E-244 on branched alpha- and beta-cyclodextrins was investigated. Glucosyl-alpha cyclodextrin (6-O-alpha-D-glucosylcyclomaltohexaose) and maltosyl-alpha cyclodextrin (6-O-alpha-D-maltosylcyclomaltohexaose) were hydrolyzed to 6(3)-O alpha-D-glucosylmaltohexaose and 6(3)-O-alpha-D-maltosylmaltohexaose, respectively. Glucosyl-beta-cyclodextrin (6-O-alpha-D-glucosylcyclomaltoheptose) and maltosyl-beta-cyclodextrin (6-O-alpha-D-maltosyclomaltohepatose) were also mainly transformed to 6(4)-O-alpha-D-glucosylmaltoheptaose and 6(4)-O-alpha-D maltosylmaltoheptaose, respectively. These results suggest that the cyclodextrin hydrolyzing enzyme cleaves branched alpha- and beta-cyclodextrins at an alpha-1,4 linkage which is located furthest from the branching point on the cyclodextrin ring. PMID- 1915864 TI - The Pro117 to glycine mutation of staphylococcal nuclease simplifies the unfolding-folding kinetics. AB - Kinetics of unfolding and refolding of a staphylococcal nuclease mutant, in which Pro117 is replaced by glycine, have been investigated by stopped-flow circular dichroism, and the results are compared with those for the wild-type protein. In contrast to the biphasic unfolding of the wild-type nuclease, the unfolding of the mutant is represented by a single-phase reaction, indicating that the biphasic unfolding for the wild-type protein is caused by cis-trans isomerization about the prolyl peptide bond in the native state. The proline mutation also simplifies the kinetic refolding. Importance of the results in elucidating the folding mechanism is discussed. PMID- 1915865 TI - Apolipoprotein D transcription occurs specifically in nonproliferating quiescent and senescent fibroblast cultures. AB - We studied apolipoprotein D (apoD) mRNA in primary cultures of human diploid fibroblasts (HDF). In early-passage HDF no apoD mRNA was detected in replicating cells in sparse culture, but the gene was expressed in quiescent cells in confluent and in serum-starved cultures. In contrast, late-passage HDF expressed apoD mRNA in sparse culture, but the level increased after attainment of confluence. Thus fibroblasts, the common cell-type expressing apoD mRNA in vivo, express this characteristic following growth-arrest. The same pattern of activation was found in another fibroblast cell line deficient in apoB/E (LDL) receptors, excluding a role for cellular cholesterol delivery by the LDL-receptor pathway controlling apoD expression. PMID- 1915866 TI - Analysis of the 5' non-coding region of rat liver S-adenosylmethionine synthetase mRNA and comparison of the Mr deduced from the cDNA sequence and the purified enzyme. AB - A 3 kb cDNA coding for rat liver S-adenosylmethionine (AdoMet) synthetase has been isolated. The Mr of the protein has been unequivocally determined by cDNA sequencing and enzyme purification on a thiopropyl-Sepharose column. The length of the mRNA 5' non-coding region has been defined by primer-extension analysis. The rat liver cloned cDNA has been also used to detect S-adenosylmethionine synthetase mRNA in human liver. PMID- 1915867 TI - Activation of c-myc promoter by c-myc protein in serum starved cells. AB - The function of the c-myc protein, the product of a proto oncogene, is not clearly understood although many reports, including ours, suggest that the c-myc protein plays several roles in the regulation of transcription and DNA replication. Here we examined the effects of c-myc protein on transcription from the c-myc promoter, and by inference its role in auto-regulation, after introducing into cultured cells a c-myc expression vector and a CAT reporter gene linked to the promoter and upstream region of the human c-myc gene. To minimize the effects of the endogenous c-myc protein on the exogenously added CAT reporter gene, the transfected cells were treated under serum-free conditions. The results show that CAT expression from the myc promoter increased in a dose-dependent manner after addition of the c-myc expression vector, and that it also required the presence of a c-myc binding sequence previously identified 2 kb upstream from c-myc's first exon. Moreover, the domains of the c-myc protein important for transactivation were determined by use of various deletions mutants of c-myc cDNA. The results showed that the N-terminal portion in the c-myc protein was necessary for transactivation beside the C-terminal portion containing basic region, helix-loop-helix, and leucine zipper. PMID- 1915868 TI - D1 protein degradation during photoinhibition of intact leaves. A modification of the D1 protein precedes degradation. AB - Illumination of intact pumpkin leaves with high light led to severe photoinhibition of photosystem II with no net degradation of the D1 protein. Instead, however, a modified form of D1 protein with slightly slower electrophoretic mobility was induced with corresponding loss in the original form of the D1 protein. When the leaves were illuminated in the presence of chloramphenicol the modified form was degraded, which led to a decrease in the total amount of the D1 protein. Subfractionation of the thylakoid membranes further supported the conclusion that the novel form of the D1 protein was not a precursor but a high-light modified form that was subsequently degraded. PMID- 1915869 TI - New evidence suggests that the initial photoinduced cleavage of the D1-protein may not occur near the PEST sequence. AB - When isolated reaction centres of photosystem 2 from pea or wheat are exposed to photoinhibitory illumination in the presence of an electron acceptor, breakdown products of the D1-protein are observed having molecular masses ranging from about 24 to 10 kDa. By using antibodies raised to the C-terminal or N-terminal portions of D1 it was shown that the major breakdown fragment of 24 kDa was derived from the C-terminus. This conclusion was supported by phosphorylation studies and from the digestion pattern obtained by lysine specific endoprotease induced proteolysis. The complementary N-terminal breakdown fragment was found to have an apparent molecular mass of 10 kDa. The implications of these data are discussed in terms of the possible relationship between the 24 kDa C-terminal fragment and the 23.5 kDa breakdown fragment detected in vivo by Greenberg et al. [1987, EMBO J. 6, 2865-2869] and it is suggested, based on limited proteolysis using papain, that the latter may not be derived from the N-terminus as previously thought but also originates from the C-terminus. PMID- 1915870 TI - Expression of an inwardly rectifying K+ channel from rat basophilic leukemia cell mRNA in Xenopus oocytes. AB - Rat basophilic leukemia cells (RBL-2H3) have previously been shown to contain a single type of voltage-activated channel, namely an inwardly rectifying K+ channel, under normal recording conditions. Thus, RBL-2H3 cells seemed like a logical source of mRNA for the expression cloning of inwardly rectifying K+ channels. Injection of mRNA isolated from RBL-2H3 cells into Xenopus oocytes resulted in the expression of an inward current which (1) activated at potentials negative to the K+ equilibrium potential (Ek), (2) decreased in slope conductance near Ek, (3) was dependent on [K+]o and (4) was blocked by external Ba2+ and Cs+. These properties were similar to those of the inwardly rectifying K+ current recorded from RBL-2H3 cells using whole-cell voltage clamp. Injection of size fractionated mRNA into Xenopus oocytes revealed that the current was most strongly expressed from the fraction containing mRNA of approximately 4-5 kb. Expression of this channel represents a starting point for the expression cloning of a novel class of K+ channels. PMID- 1915871 TI - Effects of cholesterol- or 7-ketocholesterol-containing liposomes on colony forming ability of cultured cells. AB - Experiments with cultured Chinese hamster cells showed that incubation of the cells with (phosphatidylcholine + cholesterol + 7-ketocholesterol)-containing liposomes (4:3:1 by weight) during two hours led to a decrease in the colony forming ability of cells down to zero, while (phosphatidylcholine + cholesterol) containing liposomes (1:1 by weight) reduce this parameter by 90%. Furthermore, the cholesterol-containing liposomes (without 7-ketocholesterol) induce a decrease in the number of the maximal-site colonies accompanied by the corresponding increase in the number of the middle-size colonies. PMID- 1915872 TI - Destabilization of Zn2+ coordination in ADP-ribose transferase (polymerizing) by 6-nitroso-1,2-benzopyrone coincidental with inactivation of the polymerase but not the DNA binding function. AB - 6-Nitroso-1,2-benzopyrone, an oxidation product of 6-amino-1,2-benzopyrone, binds to the DNA-recognizing domain of the ADP-ribose transferase protein and preferentially destabilizes Zn2+ from one of the two zinc finger polypeptide complexes present in the intact enzyme, as determined by the loss of 50% of 65Zn2+ from the 65Zn(2+)-isolated protein molecule, coincidental with the loss of 99% of enzymatic activity. The 50% zinc-deficient enzyme still binds to a DNA template, consisting of a 17-mer DNA primer annealed to M13 positive strand, resulting in the blocking of DNA synthesis by the Klenow fragment of Pol I. Auto poly-ADP-ribosylated ADP-ribose transferase, which is the probable physiological state of this protein in intact cells, does not bind to primer-template DNA and does not block DNA synthesis by the Klenow fragment. On the basis of this in vitro model it is proposed that molecules which inhibit or inactivate ADP-ribose transferase in intact cells can induce significant alteration in DNA structure and replication. PMID- 1915873 TI - Localization of subunits in proteasomes from Thermoplasma acidophilum by immunoelectron microscopy. AB - The subunit topography of the Thermoplasma acidophilum proteasome was determined by immunoelectron microscopy using monospecific antibodies directed against the two constituent subunits (alpha,beta). Anti-alpha-subunit IgG was found to bind to the outer disks of the cylinder- or barrel-shaped molecule, while the binding sites of the anti-beta-subunit IgG were mapped on the two inner rings. Probably the homologues of the two subunits in the compositionally more complex but isomorphous eukaryotic proteasomes occupy equivalent positions. PMID- 1915874 TI - NMR studies of [U-13C]cyclosporin A bound to human cyclophilin B. AB - NMR data (1H and 13C chemical shifts, NOEs) on [U-13C]cyclosporin A bound to cyclophilin B were compared to previously published data on the [U-13C]CsA/CyPA complex [Fesik et al., (1991) Biochemistry 30, 6574-6583]. Despite only 64% sequence identity between CyPA and CyPB, the conformation and active site environment of CsA when bound to CyPA and CyPB are nearly identical as judged by the similarity of the NMR data. PMID- 1915875 TI - Reactions of the alpha-tocopheroxyl radical in micellar solutions studied by nanosecond laser flash photolysis. AB - Laser flash photolysis of alpha-tocopherol in methanol and in aqueous micellar solutions has been shown to produce the alpha-tocopheroxyl radical. The reaction between the alpha-tocopheroxyl radical and ascorbate in positively charged hexadecyltrimethylammonium chloride (HTAC) micelles occurred with a second order rate constant of 7.2 x 10(7) M-1.s-1, whereas in negatively charged sodium dodecyl sulphate (SDS) micelles the rats constant was only 3.8 x 10(4) M-1.s-1. The alpha-tocopheroxyl radical was found to be relatively long-lived in HTAC micelles (t1/2 greater than or equal to 5 min), allowing the slow disappearance of the alpha-tocopheroxyl radical by reaction with glutathione to be observed. PMID- 1915876 TI - Biosynthesis of ferulic acid esters of plant cell wall polysaccharides in endomembranes from parsley cells. AB - A microsomal preparation from suspension-cultured parsley cells is able to transfer ferulic acid from the respective CoA thioester to endogenous acceptors. The reaction is not enhanced by digitonin but stimulated by Mg2+, Ca2+ and Co2+. Spermine can partly replace divalent ions. Solubility properties and degradation by polysaccharide hydrolases suggest that the products are polymeric cell wall carbohydrates. Sucrose density gradient centrifugation revealed that the most active vesicle fraction is distinct from plasma membranes but does also not peak with IDPase. It is suggested that a subfraction of the Golgi-apparatus is the source of enzyme and acceptors. PMID- 1915877 TI - The retarded rate of acid-catalyzed solvolysis of glycoside bonds between reducing-end glucose residue and ceramide in glycosphingolipids compared with that of glycoside bonds between hexopyranosides. AB - Rates of acid-catalyzed solvolysis of glycoside bonds in glycosphingolipids were compared to establish a basis for conducting saccharide analysis. Permethylated globotetraosylceramide and asialogangliotriaosylceramide as model compounds for methylation and sugar composition analysis, respectively, were solvolyzed under acidic conditions and the sugar components thus obtained were determined at specified times by gas liquid chromatography, after they had been derivatized. Reducing-end glucose residues in both compounds were liberated more slowly than other sugar residues. Glycoside bonds between reducing-end glucose and ceramide in glycosphingolipids would thus appear to be more resistant towards acid catalysed solvolysis than other glycoside bonds between hexopyranosides. PMID- 1915878 TI - Presence of phospholipase C in coated vesicles from bovine brain. Dual regulatory effects of GTP-analogs. AB - Bovine brain coated vesicles display free calcium-dependent phospholipase C activity. Gpp(NH)p and GTP gamma S inhibited phospholipase C at nanomolar concentrations. Increasing concentrations of Gpp(NH)p and GTP gamma S reversed the inhibitory effects and stimulated phospholipase C activity. Preincubation of coated vesicles with pertussis toxin blocked the poorly-hydrolyzable GTP-analogs' inhibitory effects on phospholipase C. These data indicate that guanine nucleotides exert a dual regulatory control of phospholipase C in coated vesicles and that the inhibitory pathway is mediated by a pertussis toxin-sensitive G protein. PMID- 1915879 TI - Overproduction, purification and crystallization of Bacillus cereus oligo-1,6 glucosidase. AB - The gene coding for oligo-1,6-glucosidase from Bacillus cereus ATCC7064 has been overexpressed in Escherichia coli MV1184 cells under the control of the lac promoter in the genetically engineered plasmid pBCE4-2. Oligo-1,6-glucosidase was purified in large quantities and was crystallized at 25 degrees C by using a hanging drop vapor diffusion method with 53% saturated ammonium sulfate. The crystals have the shape of hexagonal bipyramids and belong to the space group P6(2) or P6(4) with lattice constants of a = b = 106.1 A, c = 120.0 A and gamma = 120 degrees. PMID- 1915880 TI - Identification of 4-chlorobenzoyl-coenzyme A as intermediate in the dehalogenation catalyzed by 4-chlorobenzoate dehalogenase from Pseudomonas sp. CBS3. AB - The intermediate in the reaction catalyzed by 4-chlorobenzoate dehalogenase from Pseudomonas sp. CBS3 was identified as 4-chlorobenzoyl-CoA. One component of 4 chlorobenzoate dehalogenase worked as a a 4-chlorobenzoyl-CoA ligase catalyzing the formation of 4-chlorobenzoyl-CoA from 4-chlorobenzoate, coenzyme A and ATP. This intermediate was detected spectrophotometrically and by HPLC. 4 chlorobenzoyl-CoA was the substrate for the dehalogenase component, which catalyzed the conversion to 4-hydroxybenzoate with concomitant release of coenzyme A. PMID- 1915881 TI - Tetanus toxin receptor. Specific cross-linking of tetanus toxin to a protein of NGF-differentiated PC 12 cells. AB - A subclone of rat pheochromocytoma cells expresses high affinity receptors for tetanus toxin on differentiation with NGF [Walton, K.M., Sandberg, K., Rogers, T.B. and Schnaar, R.L. (1988) J. Biol. Chem. 263, 2055-2063]. In the presence of protein cross-linking agents, [125I]tetanus toxin, bound to these cells at 0 degree C, forms a cross-linked product with apparent molecular weight of 120 kDa. The formation of [125I]tetanus toxin conjugate involves the heavy chain of the toxin, is prevented by cold toxin and it is largely reduced by pretreating cells with proteases. The cross-linked product is formed only upon incubation of the toxin with NGF-differentiated cells. These results suggest that a protein with apparent molecular weight of 20 kDa is involved in the neurospecific binding of tetanus toxin. PMID- 1915882 TI - Alkyllysophospholipid ET-18-OCH3 acts as an activator of protein kinase C in HL 60 cells. AB - HL-60 cells are very sensitive to the cytotoxic action of ether lipids. Several hypotheses have been proposed to explain this cytotoxicity. We investigated the influence of the alkylphospholipid ET-18-OCH3 on the activity of protein kinase C. HL-60 cells were incubated with ET-18-OCH3 at a concentration of 20 micrograms/ml for 4 h. After the incubation the membrane fraction of the HL-60 cells was isolated and the activity of protein kinase C was determined while it was still associated with the membrane, using the synthetic peptide substrate [Ser25]-protein kinase C (19-31) as a protein kinase C specific substrate. The activity of the membrane-bound protein kinase C was increased in HL-60 cells treated with ET-18-OCH3 compared to untreated HL-60 cells. The increase in protein kinase C activity was not a consequence of translocation and appeared to be additive to the effect of the phorbol ester 12-myristate 13-acetate. In contrast, solubilized protein kinase C from HL-60 cells could be inhibited or stimulated in vitro by ET-18-OCH3, dependent on the mode of addition of ET-18 OCH3 and phospholipids. PMID- 1915883 TI - Folding intermediates of hyperthermophilic D-glyceraldehyde-3-phosphate dehydrogenase from Thermotoga maritima are trapped at low temperature. AB - D-Glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic eubacterium, Thermotoga maritima, is extremely thermostable showing a thermal transition beyond 105 degrees C. At low temperature, 'cold denaturation' becomes detectable only in the presence of destabilizing agents. Reconstitution after preceding denaturation depends on temperature. At 0 degree C, no significant recovery of activity is detectable, whereas between 30 and 100 degrees C reactivation reaches up to 85%. Shifting the temperature from low values to the range of optimum reconstitution releases the trapped intermediate in a fast reaction. Evidence from ultra-centrifugal analysis and far-UV circular dichroism proves the intermediate to be partially assembled to the tetramer, with most of its native secondary structure restored in a fast reaction. Fluorescence emission exhibits at least biphasic kinetics with the rate-limiting step(s) reflecting local adjustments of aromatic residues involved in tertiary contacts in the native state of the enzyme. PMID- 1915884 TI - Tunicamycin inhibits the initiation of DNA synthesis stimulated by prostaglandin F2 alpha in Swiss mouse 3T3 cells. AB - Tunicamycin, an inhibitor of the asparagine-linked protein N-glycosylation, blocks the initiation of DNA synthesis in Swiss 3T3 cells stimulated by prostaglandin F2 alpha alone or with insulin. This effect is exerted only when tunicamycin is added from 0 to 8 h after stimulation and it decreases the rate of entry into S phase. Blocking of labeled sugar incorporation to proteins occurs regardless of the time of PGF2 alpha stimulation. In contrast tunicamycin does not inhibit protein synthesis. These results suggest that N-glycoprotein synthesis early during the prereplicative phase is an important event controlling the mitogenic action of PGF2 alpha. PMID- 1915885 TI - Human Zn-alpha 2-glycoprotein cDNA cloning and expression analysis in benign and malignant breast tissues. AB - Two cDNA clones coding for Zn-alpha 2-glycoprotein (Zn-alpha 2-gp) have been isolated from a human breast library and their nucleotide sequences determined. The deduced amino acid sequence contains the coding information for a hydrophobic signal peptide and the 278 residues of the mature protein. Comparison of this sequence with that from the protein purified from plasma reveals four differences: two amino acid changes (Gln-67 and Glu-222) and insertion of two residues (Ile-75 and Phe-76). Northern-blot analysis showed that the Zn-alpha 2 gp gene is expressed in liver and normal breast, but not in placenta, ovary and thyroid. A comparative analysis in mammary tissues from women with different diseases revealed enhanced expression of Zn-alpha 2-gp gene in benign breast lesions and a variable expression level in breast cancers. PMID- 1915886 TI - Two proteins act as the IUF1 insulin gene enhancer binding factor. AB - IUF1 is a pancreatic beta cell-specific factor which binds to the sequence 5' CPyCTAATG-3' (CT box) within the human insulin gene enhancer. Here we show that IUF1 is composed of 2 binding activities that can be separated by DEAE ion exchange chromatography. South Western blot analysis indicates that these distinct binding activities have apparent molecular weights of 115 kDa and 46 kDa. PMID- 1915887 TI - Molybdopterin adenine dinucleotide and molybdopterin hypoxanthine dinucleotide in formylmethanofuran dehydrogenase from Methanobacterium thermoautotrophicum (Marburg). AB - Formylmethanofuran dehydrogenase from Methanobacterium thermoautotrophicum was purified to apparent homogeneity and found to contain per mol (apparent molecular mass 110 kDa) 0.6 mol molybdenum, 4 mol non-heme iron, 4 mol acid-labile sulfur, and in addition, 0.7 mol of a pterin-containing co-factor (apparent molecular mass 800 Da) which has been characterized. The pterin material was extracted after alkylation by iodoacetamide and the extract subjected to HPLC on Lichrospher 100 RP-18. Three pterin compounds were resolved. On the basis of their UV/visible spectra and of the products formed after cleavage by nucleotide pyrophosphatase and alkaline phosphatase they were identified as the [di(carboxamidomethyl)]-derivatives of molybdopterin guanine dinucleotide (MGD), of molybdopterin adenine dinucleotide (MAD), and of molybdopterin hypoxanthine dinucleotide (MHD). The three pterin dinucleotides were present in the proportions 1:0.4:0.1. PMID- 1915888 TI - Distribution of glutathione peroxidases and glutathione reductase in rat brain mitochondria. AB - The distribution of glutathione reductase (GR), glutathione peroxidase (GPx) and phospholipid hydroperoxide glutathione peroxidase (PHGPx) in isolated rat brain mitochondria was investigated, using a fractionation procedure for the separation of inner and outer membranes, contact sites between the two membranes and a soluble fraction mainly originating from the mitochondrial matrix. The data indicate that GR and GPx are concentrated in the soluble fraction, with a minor portion of the two enzymes being associated with the contact sites. PHGPx is localized largely in the inner membrane. The possible functional significance of these findings is discussed. PMID- 1915889 TI - Analysis of the polyadenylation consensus sequence context in the genes of nuclear encoded mitochondrial proteins. AB - A compilation of the pre-mRNA ends of the genes of nuclear encoded mitochondrial proteins resulted in a consensus sequence of the type (T/A)NTTNNNNNTTTNAATAAA. Nucleotide positions +8, +13, +14, +16 and +17 downstream of the AATAAA sequence show also a predominance of nucleotide T. This consensus sequence suggests the importance of the immediate surroundings of the cannonical polyadenylation signal sequence AATAAA on the efficiency of the cleavage and polyadenylation of this specific group of pre-mRNAs. PMID- 1915890 TI - In vitro activation of the Saccharomyces cerevisiae Ras/adenylate cyclase system by glucose and some of its analogues. AB - Using crude membrane preparations of Saccharomyces cerevisiae, we have demonstrated that glucose and glucose analogues which are not efficiently phosphorylated activate the guanine nucleotide-dependent adenylate cyclase in vitro. The activation appears to be mediated by the Ras proteins. Moreover, data are presented indicating that glucose and its analogues activate adenylate cyclase by stimulating the exchange of guanine nucleotides at its regulatory component. Thus, it has been possible to show the action of a physiological effector on the nucleotide exchange reaction in a member of the ras superfamily. PMID- 1915892 TI - The calpain-calpastatin system in vascular smooth muscle. AB - Vascular smooth muscle contains large amounts of the Ca(2+)-dependent protease calpain II. In this study, we compared bovine aortic muscle (muscle phenotype) to cultured bovine aortic cells of smooth muscle origin (modulated phenotype) with respect to major constituents of the calpain-calpastatin system. Bovine aortic muscle contained only calpain II by activity measurements, Western blot of tissue extracts and Northern blot of poly(A)+ RNA. On the other hand, using the same methodologies, both calpains I and II as well as the 110 kDa inhibitor protein, calpastatin, were identified in cultured bovine aortic cells of smooth muscle origin. We conclude that the phenotypic state of smooth muscle cells is associated with differential expression of major components of the calpain calpastatin system. Moreover, bovine aortic muscle is the only tissue identified to date that contains calpain II exclusively. PMID- 1915891 TI - On the mechanism of oligomycin inhibition of Ca(2+)-induced mitochondrial respiration. AB - The addition of oligomycin in the presence of Ca2+ increased the ADP pool in mitochondrial suspension. It is suggested that oligomycin inhibition of Ca(2+) induced mitochondrial respiratory activation is the function of the increased endogenous ADP pool. Low ADP concentrations (5-20 microM) produce the same inhibitory effect as oligomycin. The increase of ADP levels in the presence of glucose plus hexokinase resulted in the inhibition of Ca(2+)-induced respiration, while the addition of phosphoenol pyruvate plus pyruvate kinase followed by a reduction in ADP levels, reversed the oligomycin inhibitory effect. One of the essential stages of ADP accumulation in mitochondrial suspensions in the presence of oligomycin and Ca2+ is proposed to be the formation of ADP from AMP and ATP, effected by adenylate kinase. PMID- 1915893 TI - Detection of the lipid-linked precursor oligosaccharide of N-linked protein glycosylation in Drosophila melanogaster. AB - The presence of a glycan of the same molecular size as the lipid linked precursor oligosaccharide (Glc3Man9GlcNAc2) of the N-linked protein glycosylation pathway in mammalian cells has been detected in a glycolipid fraction of cultured Drosophila melanogaster cells. Oligosaccharide sequencing studies were consistent with the existence of a glucosylated high mannose containing structure, which may be the common precursor for N-linked protein glycosylation in insect cells. PMID- 1915894 TI - Cloning of the D-lactate dehydrogenase gene from Lactobacillus delbrueckii subsp. bulgaricus by complementation in Escherichia coli. AB - A strain of Escherichia coli (FMJ144) deficient for pyruvate formate lyase and lactate dehydrogenase (LDH) was complemented with a genomic DNA library from Lactobacillus delbrueckii subsp. bulgaricus. One positive cloned showed LDH activity and production of D(-)lactate was demonstrated. The nucleotide sequence of the D-LDH gene (ldhA) revealed the spontaneous insertion of an E. coli insertion sequence IS2 upstream of the gene coding region. The open reading frame encoded a 333-amino acid protein, showing no similarity with known L-LDH sequences but closely related to L. casei D-hydroxyisocaproate dehydrogenase (D HicDH). PMID- 1915895 TI - Formation and crystallization of Thermus thermophilus 70S ribosome/tRNA complexes. AB - 70S ribosomes from Thermus thermophilus are able to form ternary complexes with N AcPhe-tRNAPhe from either Thermus thermophilus or Escherichia coli, in the presence of a short oligo(U) of six or nine uridines. A complex of N-AcPhe tRNAPhe/(U)9/70S ribosome from Th. thermophilus was crystallized under the same conditions used for the growth of crystals from isolated ribosomes (S.D. Trakhanov, et al., (1987) FEBS Lett. 220, 319-322). PMID- 1915896 TI - Strong expression of foreign genes following direct injection into fish muscle. AB - We report here for the first time direct injection of genes into fish muscle in vivo. Plasmids used contain either SV40 early promoter, rabbit beta-cardiac myosin heavy chain promoter, human MxA promoter or an artificial promoter, fused to a chloramphenicol acetyltransferase (CAT) or beta-galactosidase reporter gene. CAT assays revealed that most gene constructs were highly expressed. Histochemical analysis showed that beta-galactosidase was strongly expressed at the site of injection within muscle fibres. This method provides an excellent system for testing expression of gene constructs, including those of mammalian origin, in fish muscle in vivo and has the potential for fish vaccination. PMID- 1915897 TI - Formation of enzyme-substrate disulfide linkage during catalysis by protein disulfide isomerase. AB - During the regeneration of native ribonuclease A (RNase) from the disulfide scrambled molecule by protein disulfide isomerase (PDI), the substrate forms a covalent intermediate with the enzyme through disulfide linkage(s). This has been shown by the appearance of a band at the molecular weight position expected in SDS-PAGE at the same time as the increase in RNase activity. The new band decreased when the regeneration of RNase activity approached completion and disappeared by treatment of the reaction mixture with excess dithiothreitol. PMID- 1915898 TI - Differential expression of laminin chains in hepatic lipocytes. AB - The lipocyte is an important source of laminin in the normal liver. We have investigated the expression of the 3 chains of laminin in isolated rat lipocytes. Both B1 and B2 chains, but not A, were found in medium from 5-day-old lipocyte primary cultures by immunoblotting and immunoprecipitation of 35S-labeled proteins after reducing SDS-polyacrylamide gel electrophoresis. An additional polypeptide of Mr = 380,000 was identified by immunoprecipitation. Under non reducing conditions only one Mr = 900,000 band was revealed. High levels of B1 and B2 mRNAs were also demonstrated in 5-day-old cultured lipocytes while at the time of seeding, only B2 chain mRNAs were clearly detectable. A chain mRNA was constantly absent. These results suggest that lipocytes produce a variant form of laminin in primary culture and that the Mr = 380,000 polypeptide could be unrelated to the A chain of laminin. PMID- 1915899 TI - Comparative study of subunits of phenylalanyl-tRNA synthetase from Escherichia coli and Thermus thermophilus. AB - FPLC separation of alpha- and beta-subunits of phenylalanyl-tRNA synthetases from E. coli MRE-600 and Thermus thermophilus HB8 has been carried out in the presence of urea. Native alpha-subunits of both enzymes were primarily alpha 2-dimers and tended to aggregate. Most E. coli enzyme beta-subunits were monomeric and only a small fraction was represented by beta 2-dimers. All thermophilic beta-subunits were beta 2-dimers. It was shown that monomers and all forms of homologous subunits had no catalytic activity in tRNA(Phe) aminoacylation. For the enzymes and their subunits, titration curves were obtained and isoelectric points were determined. The comparison of the relative surface charges indicated similarity of the surfaces of entire enzymes and the corresponding beta-subunits. Alpha subunits displayed a distinctly different pH dependence of the surface charge. A spatial model of the oligomeric structure and a putative mechanism for its formation are discussed. PMID- 1915900 TI - Surgical thrombectomy for ilio-femoral venous thrombosis. PMID- 1915901 TI - Follow-up after reconstructive arterial surgery. PMID- 1915902 TI - Isolated iliac aneurysms. AB - Isolated iliac aneurysms are relatively infrequent, often difficult to detect and therefore rarely considered in the differential diagnosis. Because of their close anatomical relationship to the ureters, bladder, colon, pelvic veins, femoral and sciatic nerve roots one is often misled. The consequences can be grave; chronic ureteric obstruction for instance can cause damage to one or both kidneys. With the growing frequency of tube grafting for aortic aneurysms it becomes increasingly important to consider the prevalence and incidence of isolated iliac aneurysms. The aim of this study is to report the incidence, clinical course and outcome of these lesions. In a consecutive series of 678 aorto-iliac aneurysms in the years 1972-1988 there were 53 isolated iliac aneurysms (7%) ranging in size from 3.5-14 cm whereas the reported incidence in the literature lies between 1 2%; the prevalence in consecutive autopsy series is even less than 1%. CT scanning proved to be the gold standard for the evaluation of pelvic aneurysmal disease whilst angiograms were of little help. A palpable mass was present in nine cases; GI-tract signs in 12 (five patients being operated on for suspicion of appendicitis or sigmoiditis), the genito-urinary tract was involved in eight cases, sciatic or femoral root nerve compression occurred in seven, recurrent pulmonary embolism in two, lower extremity ischaemia in seven and a-v fistula in one. The male:female ratio was 51:2 and that of ruptured to non-ruptured aneurysms 15:38. The site of isolated iliac aneurysms was the common and/or the internal iliac artery uni- or bilaterally. The external iliac artery was never involved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915903 TI - Magnetic resonance morphological, chemical shift and flow imaging in peripheral vascular disease. AB - We have used magnetic resonance imaging to study the aorto-iliac region in 13 patients with peripheral disease. Five healthy volunteers were studied for comparison. Magnetic resonance spin-echo imaging, chemical shift imaging to determine lipid content of atheroma, phase-shift velocity mapping and quantitative flow studies were obtained and the findings compared with radiological angiograms. The velocity profiles study showed an increased velocity at the site of a stenosis in eight patients who had iliac artery disease. Quantitative flow measurements made in both iliac arteries and the aorta in five patients and five volunteers showed a flow ratio in both iliac arteries less than 0.85 in patients with a stenosis of one iliac artery and a ratio greater than 0.85 in the volunteers. In one patient studied before and after angioplasty, flow improved post-angioplasty. The flow curve showed a characteristic distortion in diseased vessels compared with healthy vessels. In the chemical shift images of aortic atheroma five were classified as fibrous and three were lipid rich. This preliminary study showed the potential of magnetic resonance to assess non invasively the morphology, composition and the haemodynamic significance of atheroma. This could be important in the study of the progression of peripheral vascular disease and its response to pharmacological and surgical intervention and in the planning treatment of lesions. PMID- 1915904 TI - The effect of preformed confluent endothelial cell monolayers on the patency and thrombogenicity of small calibre vascular grafts. AB - Endothelial cell seeding has been proposed as a method to improve the patency rates in small calibre prosthetic vascular grafts. The seeding methods used at present leave much of the graft luminal surface devoid of endothelial cells and thus still significantly thrombogenic. We have developed a method to preform confluent endothelial cell monolayers, on the grafts prior to implantation, and this study investigates the effect of these monolayers on the early thrombogenicity and patency of polytetrafluoroethylene (PTFE) grafts. Small diameter PTFE grafts were seeded with canine endothelial cells obtained from the external jugular vein. Each of five dogs then received a graft seeded with its own cells and a contralateral, non-seeded control graft. At 1 and 10 weeks after graft implantation graft thrombogenicity was assessed by the use of Indium labelled platelets. The thrombogenicity index (TI) of each graft was determined from counts of gamma activity recorded over a period of 7 days. Grafts were subsequently removed at 12 weeks. At 1 week the mean TI for the seeded grafts was 0.123 (SD 0.019) and that for the controls 0.183 (SD 0.017) (p = 0.005). At 10 weeks only the seeded grafts could be assessed because all of the control grafts had occluded. At this point in time the seeded grafts had a mean TI of 0.159 (SD 0.011) (p = 0.047 vs. seeded at 1 week). By the time of removal at 12 weeks, all control grafts were occluded but only one of the seeded grafts had occluded (p = 0.025). In conclusion, the use of preformed, confluent endothelial cell monolayers for seeding prosthetic grafts significantly reduces the early graft thrombogenicity and improves graft patency. It does not, however, completely halt the increase in thrombogenicity which occurs during the early post-implantation period. PMID- 1915905 TI - Muscle ATP and lactate and the release of myoglobin and carbanhydrase III in acute lower-limb ischaemia. AB - Serum-myoglobin and carbanhydrase III (S-CAIII), a specific muscle enzyme, were measured on admission, during surgery and in the postoperative period in 23 patients with acute lower-limb ischaemia and in 21 patients with chronic limb ischaemia in order to evaluate these molecules as possible markers of the degree of clinical ischaemia. The muscle contents of ATP and lactate were determined in muscle biopsies from patients with acute ischaemia on admission. Unlike S myoglobin and S-CAIII they discriminated between cases which required subsequent amputation from those which did not. Clinical signs of ischaemia were, however, of no value in this respect and there were no correlations between clinical signs or the duration of ischaemia and S-myoglobin or S-CAIII or the contents of ATP or lactate in muscle tissue. The levels of S-myoglobin and S-CAIII correlated well (r = 0.95, p less than 0.0001). In patients who subsequently required an amputation S-myoglobin increased ten-fold (i.e., from 24-48 h postoperatively in acute arterial ischaemia and from 3 h postoperatively in patients with chronic limb ischaemia). In patients with a successful revascularisation S-myoglobin returned to normal levels. It is concluded that in this investigation S-myoglobin had no prognostic value on admission and that S-myoglobin analyses in the postoperative course may be useful for making clinical decisions concerning impending recirculation failures. PMID- 1915906 TI - Duplex scanning alone before carotid endarterectomy: a 5-year experience. AB - The role of duplex scanning and arteriography as a means of assessing patients for carotid endarterectomy has been reviewed for the period 1984 to 1988 when 98 carotid endarterectomies were performed. Of these 44 were selected for surgery on the basis of duplex assessment alone, 48 after carotid angiography and duplex scanning and six after angiography alone. No difference between the groups of patients was observed for either perioperative or follow-up complication rates, although all late deaths occurred in patients who had been examined by angiography. By the end of the study period angiography was requested for less than 30% of all patients undergoing carotid endarterectomy. It is argued that the change in our practice is safe provided that certain criteria are met. These include angiography in cases of suspected aortic arch or proximal vessel disease and in those symptomatic patients with a duplex diagnosis of complete occlusion. PMID- 1915907 TI - Revascularisation for a poorly functioning solitary kidney. AB - Renovascular disease in a solitary kidney is a difficult and challenging problem. In six patients, with a mean age of 62 years, revascularisation was undertaken. In four of them, one to three attempts at PTA were made before the operation but all were unsuccessful. The preoperative mean serum creatine (Cr) was 3.52 mg% (range 2.5-5.5). The stenoses were caused by atherosclerosis in five cases and fibromuscular dysplasia (FMD) in one. Two methods of revascularisation were used: aortorenal bypass with saphenous vein (three patients) or PTFE (two patients), and transaortic renal endarterectomy with a venous patch (one patient). One patient with an aortic aneurysm underwent simultaneous aortic repair with a PTFE graft. There was no mortality or major complications in our series and no patient suffered acute tubular necrosis (ATN) after surgery. The mean follow-up period was 51 months (15-84 months). Postoperative Cr and blood pressure improved in all patients. Four patients no longer required any medication and the other two only needed reduced doses of antihypertensive drugs. Based on our experience of patients with poor single kidney function, we do not recommend PTA in this specific group of patients and suggest an aggressive surgical approach, which can effectively improve solitary kidney function, thus eliminating further haemodialysis. PMID- 1915908 TI - Aorto-iliac/femoral reconstructions in patients with vasculogenic impotence. AB - One hundred and forty-eight patients out of 386 undergoing aorto-iliac or aortofemoral bypass had preoperative impotence, 37 of these were diabetics. In all of them Doppler studies revealed a penile/brachial pressure index less than 0.6 and an abnormal waveform analysis. Nocturnal penile tumescence was investigated in 44 cases and found to be abnormal. Angiography showed unilateral or bilateral obstructive lesions of the hypogastric arteries in 80%, in addition to aortic, common and external iliac and femoral lesions. One hundred and thirty patients (87.8%) had straight aorto-iliac/femoral bypass grafts inserted without a direct attempt to revascularise the hypogastric arteries but 24 had distal anastomoses to the bifurcation of the common iliac artery. In the remaining 18 patients the hypogastric artery was reconstructed on one side by an additional bypass or reimplantation on the graft. In 22 of 106 patients (20.7%) undergoing aortofemoral bypass, 18 of 24 (75%) with the distal anastomosis to the iliac bifurcation, and 14 of the 18 (77.7%) with revascularisation of the hypogastric arteries, erectile function was regained. A good result was obtained in only five of the diabetic patients (13.5%). Our experience suggests that: (1) impotence, as indicated by non-invasive investigations, was vasculogenic in origin since patients with the most effective revascularisation of the hypogastric arteries had the best results; (2) when it is feasible, revascularisation of the hypogastric arteries should be carried out more often, during the aorto-iliac or aortofemoral reconstructions, particularly in younger impotent patients; (3) aorto-iliac revascularisation restores potency in only a few diabetic patients. PMID- 1915910 TI - The selection of amputation level: an approach using decision analysis. AB - The choice of level for a major amputation of the leg depends upon the careful balancing of the advantages of preserving the knee joint against the risks of failure to heal and subsequent revision of the amputation stump. A study has been carried out to measure the values that health care professionals put upon different levels of disability resulting from amputation. The results show that the reduction of quality of life is thought to be 5-10% and 10-20%, respectively, for ambulation upon a below-knee and above-knee prosthesis and about 50% for failure to mobilise on an artificial limb. These utilities have been incorporated into a decision analysis to determine the optimum strategy for evaluation of amputation level, with other probabilities obtained from published data. The results demonstrate the advantage of attempting to preserve the knee joint, even if the chance of primary healing is as low as 20%. Tests of likely healing are most useful if the sensitivity is high, with specificity being less important, and the advantages may be outweighed by the costs of false negatives if sensitivity is below 90%. Sensitivity analysis shows that these findings remain valid over a wide range of possible values. Further research is required to gain more accurate information on which to base decisions, but on current evidence a policy of below-knee amputation in all cases of clinical doubt may be preferable to the use of currently available tests. PMID- 1915909 TI - PTFE or HUV for femoro-popliteal bypass: a multi-centre trial. AB - Despite wide clinical experience the choice between human umbilical vein (HUV) or polytetrafluoroethylene (PTFE) when the saphenous vein is inadequate remains unclear. In a multi-centre trial of 801 femoro-popliteal bypasses, autogenous vein could not be used in 252 (31%), of which 191 were randomised to either HUV or PTFE and started on aspirin 300 mg plus dipyridamole 150 mg (ASA + DPM) twice daily. Graft patency measured objectively by independent trial coordinators was expressed on an "intention to treat" basis by life table and analysed statistically by log rank and confidence intervals (95% CI). Overall, 101 grafts failed and cumulative patency was 53% (45-61%) at 3 years compared with 60% (55 65%) in 549 vein grafts. Prosthetic bypass patency above knee was 65% (55-75%); markedly better than 35% (23-47%) below knee (p less than 0.001) and comparable with 62% (55-69%) in 217 above knee saphenous vein grafts. Most failures occurred early at a rate of 52/1000 patient-months in the first 3 months (43/1000 for vein) falling to 21/1000 by 6 to 12 months and around 10/1000 subsequently. Randomisation produced comparable groups of 87 HUV and 104 PTFE grafts. Cumulative primary patency for HUV was 68, 63 and 57% at 1, 2 and 3 years, respectively compared with 61, 56 and 48% for PTFE with wide confidence intervals for the difference at 3 years (-20 to 38%, p = 0.27).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915911 TI - Computerised vascular data management: a flexible modular registry suitable for the evaluation of long-term results in patients subjected to multiple interventions. AB - We have designed a computerised vascular registry (CVR) combining storage of complete patient histories in minute detail, including reoperations and long-term follow-up, with clinical applicability. The basic concept of this registry is the storage of data in a structure of cycles (one cycle per treatment episode), modules (clusters of logistically correlated data) and data-chapters (clusters of clinically correlated data). The registry was designed to minimally interfere with routine clinical practice, for instance by collecting the data step-by-step at the wards and out-patient clinics, quite similar to traditional record keeping. The CVR enables production of inventories of all stored data. More importantly, and in addition to other registries, the structure of our registry adequately enables analyses of data of patients with multiple interventions and patients with long-term follow-up. A microcomputer was used for the input of data, which were stored in a structure enabling effortless transportation of the data to a mainframe computer. Standard software programs were used. Simple inventories and analyses were performed on a microcomputer, and a mainframe computer was used for more complex analyses. The performance and applicability of the newly designed CVR was thoroughly tested in comprehensive retrospective studies. On the basis of these experiences several adjustments were carried out after which the CVR was introduced into clinical practice. PMID- 1915912 TI - Z-plasty of abdominal aortic aneurysm sac to prevent aortoduodenal fistula. PMID- 1915913 TI - A simple means of access for harvesting the lesser saphenous vein. AB - Enhanced patient expectations combined with improvements in vascular technique have increased the number of lower limb arterial bypass operations performed. The natural consequence is a parallel increase in the number of re-operations for failed or failing bypasses where the optimal conduit--the ipsilateral long saphenous vein has already been used. Indeed, there are many occasions where the long saphenous vein cannot be utilised at the primary operation, either because of the demands of coronary artery bypass surgery, or because of the presence of phlebitic vein segments. As autologous vein is generally preferred to prosthetic material for distal (tibial) bypasses, the vein must be harvested from other sites. Frequently there is insufficient or inadequate arm vein from a single source. Also, there is a natural reluctance to use the contralateral long saphenous vein, even if it is still available, because of the potential need for an arterial bypass on that side. The short saphenous vein is a valuable alternative. We describe a simplified approach (compared to the more conventional posterior approach) to harvest this vein which can then be used either in isolation or in combination with a superficial femoral endarterectomy or as part of a composite vein graft. PMID- 1915914 TI - Cauda equina syndrome associated with an aorto-caval fistula. PMID- 1915915 TI - Pseudoaneurysm resulting from avulsion of the right renal artery: endoaneurysmal bypass. PMID- 1915916 TI - Aortic aneurysm repair in a renal transplant patient: preservation of renal function. PMID- 1915917 TI - False aneurysm of the abdominal aorta in Behcet's disease. PMID- 1915918 TI - Heparin for axillary vein thrombosis. PMID- 1915919 TI - Audit by envelope. PMID- 1915920 TI - Playing POSSUM with ruptured aneurysms. PMID- 1915921 TI - [The problems of the contacts of medical personnel with gynecologic patients]. PMID- 1915922 TI - [Stress and immunity]. PMID- 1915923 TI - [The difficult delivery of the fetal shoulders]. PMID- 1915924 TI - [The antenatal diagnosis of fetal status]. PMID- 1915925 TI - [Acute leukemia in children]. PMID- 1915926 TI - [Injuries to the cervical spine]. PMID- 1915927 TI - [Male pseudohermaphroditism]. PMID- 1915928 TI - [2 tables for calculating the amount of glucose and insulin doses for parenteral administration]. PMID- 1915929 TI - [The intimate world of the young family]. PMID- 1915930 TI - [The work experience of a polyclinic day hospital]. PMID- 1915931 TI - [The status and outlook for the training of specialists with a paramedical education in the USSR]. PMID- 1915932 TI - [Drug preparations for managing the hypertensive crisis]. PMID- 1915933 TI - [L. N. Svift-Gornova]. PMID- 1915934 TI - [The fixed-period work contract and its types]. PMID- 1915935 TI - The basic infertility investigation. PMID- 1915936 TI - Is the inappropriate gonadotropin secretion of patients with polycystic ovary syndrome similar to that of patients with adult-onset congenital adrenal hyperplasia? AB - OBJECTIVE: To assess gonadotropin alterations in adult-onset congenital adrenal hyperplasia (CAH) and to compare these findings with those of patients with polycystic ovary syndrome (PCOS) in an effort to better understand the pathophysiology of these abnormalities. DESIGN: Prospective study of 9 newly diagnosed patients with CAH, 10 with PCOS, and 10 ovulatory controls. INTERVENTIONS: Baseline measurements of serum androgens, progestins, estradiol (E2), estrone (E1), unbound E2, luteinizing hormone (LH), and follicle stimulating hormone (FSH). Serum LH and FSH were measured after intravenous gonadotropin-releasing hormone (GnRH) and in 15-minute blood samples for 6 hours to determine LH pulsatility. RESULTS: Serum androgens were elevated but comparable in the two patient groups. Serum LH was also elevated (P less than 0.05) but was higher in PCOS than CAH. Serum LH:FSH ratios were similar as were the responses to GnRH. Serum E1 was elevated only in PCOS, but unbound E2 was elevated to the same degree in both PCOS and CAH (P less than 0.05). Patients with PCOS had a decreased LH interpulse interval compared with controls and CAH (P less than 0.05), but LH pulse amplitude was increased in both PCOS and CAH (P less than 0.05). Serum E2 and unbound E2 correlated significantly with LH (P less than 0.05), LH responses to GnRH as well as to LH pulse amplitude in CAH (P less than 0.05). The LH interpulse interval did not correlate with estrogen in any group. None of the LH parameters correlated with serum progestin levels in CAH. CONCLUSIONS: The gonadotropin abnormalities of CAH appear to be intermediate between those of controls and PCOS. Although elevated estrogen may explain these abnormalities in CAH, additional factors may be operative in PCOS. PMID- 1915937 TI - Gonadotropin pulsatility in a stimulated cycle: clomiphene citrate increases pulse amplitudes of both luteinizing hormone and follicle-stimulating hormone. AB - OBJECTIVE: To elucidate gonadotropin secretory patterns during ovarian hyperstimulation for in vitro fertilization. DESIGN: All volunteers who attended the unit during a period of 3 months were prospectively investigated. SETTING: Infertility unit of the University Central Hospital of Oulu. PARTICIPANTS: Normally menstruating tubal infertility patients (n = 8) and healthy women with ovulatory cycles (hospital personnel, n = 11). All patients finished the study. INTERVENTIONS: Clomiphene citrate (CC), 50 mg, was administered on cycle days 5 to 9 and 300 IU of pure follicle-stimulating hormone (FSH) on cycle day 7 and 150 IU on cycle day 8. MAIN OUTCOME MEASURES: Serum samples for luteinizing hormone (LH) and FSH measurements were collected at 10-minute intervals for 6 hours on cycle day 7 (effect of CC) and day 9 (effect of CC/FSH), and the data were analyzed with the Munro computer program. RESULTS: The number of LH peaks was identical in the controls and study subjects on cycle days 7 and 9, whereas the pulse amplitude (P less than 0.025) and the pulse area (P less than 0.01) were higher in the CC/FSH-treated patients. The increase in overall mean LH level during the hormone therapy was not significant. In the CC/FSH-treated women, a decreased number of FSH pulses (P less than 0.01) with increased amplitude (P less than 0.001) and pulse area (P less than 0.01) was found. Clomiphene citrate treatment increased the mean FSH level (control versus cycle day 7, P less than 0.05) which was further increased (cycle day 7 versus cycle day 9, P less than 0.05) by FSH administration on cycle days 7 to 8. Otherwise pure FSH was found to be unable to modify endogenous LH or FSH secretory patterns under these conditions. CONCLUSIONS: Clomiphene citrate increases the amplitudes of both LH and FSH pulses in the midfollicular phase of a stimulated cycle, an effect which is not influenced by pure FSH administration. PMID- 1915938 TI - Segregation analysis and genetic counseling when both parents carry balanced chromosomal translocations. AB - OBJECTIVE: To assess the risk of chromosomally abnormal offspring and discuss counseling approach when both parents carry balanced translocations. DESIGN: Theoretical segregation analysis is performed and use of empiric data is used in genetic counseling. SETTING: Patients are referred to Division of Reproductive Genetics at the University of Tennessee, Memphis. PATIENTS, PARTICIPANTS: The mother, heterozygous for reciprocal translocation 46,XX, rcp(7;13)(p21;q22) and father, heterozygous for Robertsonian translocation 45,XY,rob(13q;14q) were referred for genetic counseling concerning risks of chromosomally abnormal offspring. INTERVENTIONS: Segregation analysis, genetic counseling, and chorionic villus sampling. MAIN OUTCOME MEASURE(S): A cumulative risk was derived to use for counseling purposes. Cytogenetics using GTG-banding was performed on cultured chorionic villus cells. RESULTS: Theoretical risk of this couple having chromosomally abnormal offspring was 40.5%. On the basis of empirical data and risk factors inherent in the specific translocations, the maternal contribution at midtrimester was 3.5%; the paternal contribution was 1% to 2%. The sum of these risks was used in counseling. CONCLUSIONS: The fetus was found to be 46,XY,rcp(7;13)(p21;q22). PMID- 1915939 TI - Lectin binding of endometrium in women with unexplained infertility. AB - OBJECTIVE: To investigate whether peri-implantation phase endometrium in women with unexplained infertility differs from the endometrium of normal fertile women. DESIGN: Assessment of the function of the endometrium by using endometrial biopsy specimens and lectin histochemistry. SETTING: Infertility Clinic, Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Eighteen normal fertile women (group I) and 18 women with unexplained infertility (group II). INTERVENTIONS: Endometrial biopsies were obtained from both groups at 5, 7, and 9 days after the luteinizing hormone (LH) surge. MAIN OUTCOME MEASURES: Five biotinylated lectins, concanavalin A (ConA), wheat germ agglutinin (WGA), soybean agglutinin, Peanut, and Ulex europaeus I were used as analytical probes to study endometrial glycoconjugates. Histochemical staining was performed using the avidin-biotin peroxidase method. The lectin binding by endometrial glands, surface epithelium, stromal cells, and vessels was assessed. RESULTS: In group I, ConA stained the subnuclear glandular cytoplasm, glandular lumen, stroma cells, and surface epithelium. In group II, ConA binding to glandular or surface epithelium was none or equivocal. In group I, WGA bound to glandular cytoplasm and stroma cells on days LH + 5 and LH + 7. In group II, WGA binding was absent in glands but present in stroma. CONCLUSIONS: Reproductive failure of women with unexplained infertility may be associated with defective biosynthesis and distribution of glycoconjugates that subsequently results in an unfavorable endometrial environment during the peri-implantation phase. PMID- 1915940 TI - Subfertility and the risk of low birth weight. AB - OBJECTIVE: We evaluated the association between subfertility and low birth weight infants. DESIGN: Women in this analysis participated in a cross-sectional investigation of maternal risk factors for adverse pregnancy outcomes. SETTING: Medical and obstetric history and life style information were obtained from women who delivered at the Boston Hospital for Women, 1977 to 1980. PATIENTS, PARTICIPANTS: Our analysis was restricted to nondiabetic married women who planned their pregnancies and subsequently delivered viable singletons (3,622). The 644 "subfertile" women (no conception during a year of unprotected intercourse) were compared with 2,978 "fertile" women (conception within 1 year). MAIN OUTCOME MEASURE(S): The relative risk of low birth weight was estimated using the cumulative incidence risk ratio. RESULTS: After adjusting for confounding, the relative risk of delivering a low birth weight infant (less than 2,500 g) for subfertile women versus fertile women was 1.9 (95% confidence interval [CI], 1.3 to 2.8). The adjusted relative risk of delivering a term low birth weight (intrauterine growth retarded) infant was 2.3 (95% CI, 1.2 to 4.4). CONCLUSIONS: In these data, subfertility is a predictor for low birth weight. The association may result from endocrinological, immunological, cervical, or other factors that interfere with optimal fetal growth. PMID- 1915941 TI - Effect of platelet-derived growth factor on endometrial stromal cell proliferation in vitro: a model for endometriosis? AB - OBJECTIVE: To assess the direct effects of platelet-derived growth factor (PDGF), a macrophage secretory product structurally and functionally similar to substances released by peritoneal macrophages isolated from endometriosis patients, on endometrial cell proliferation. DESIGN: Prospective analysis of cell proliferation in vitro. SETTING: Proliferative phase endometrial stromal cells isolated from biopsy specimens were grown in short-term culture and served as a model for stromal components of endometriotic implants. PATIENTS: Biopsies were obtained from regularly cycling volunteers without endometrial pathology. INTERVENTIONS: Platelet-derived growth factor was added to nutrient medium in both the presence and absence of suboptimal (2.5%) calf serum (CS) supplements and a physiological estradiol (E2) concentration (10(-9) M). MAIN OUTCOME MEASURES: Cumulative [3H]-thymidine incorporation as a reflection of cell proliferation. RESULTS: Platelet-derived growth factor exerted a significant dose dependent effect on stromal cell proliferation in both the presence and absence of CS (P less than 0.01). This effect was enhanced in, at best, an additive but not synergistic manner by E2 10(-9) M. CONCLUSION: These data imply that macrophage secretory products such as PDGF may play a significant role in the maintenance or proliferation of endometriosis. PMID- 1915942 TI - Guidelines for the provision of psychological evaluations for infertile patients at the University of Connecticut Health Center. AB - OBJECTIVE: Because of the psychologically demanding nature of infertility treatment, it has been recommended that psychological services be made available to infertile patients. However, no specific guidelines for the scope or usage of those services has been proposed. Our objective was to formulate guidelines to be used at our institution to provide psychological evaluations to infertility patients. DESIGN: The guidelines were formulated through discussions between the division psychologist and attendings and then presented to and modified by the University Ethics, Risk Management, Legal, and Institutional Review Board departments. SETTING: The University of Connecticut Health Center Division of Reproductive Endocrinology and Infertility provides tertiary level care to infertility patients. Services include assisted reproductive technologies and donor gamete programs. Surrogate parenting is not a provided service. RESULTS: Guidelines for the provision and use of psychological services for infertility patients were formulated. CONCLUSIONS: These guidelines are preliminary in nature and intended to provide a starting point for discussion among physicians, nurses, and mental health professionals regarding the psychological needs of infertility patients. PMID- 1915943 TI - Risk factors for ectopic pregnancy in 556 pregnancies after in vitro fertilization: implications for preventive management. AB - OBJECTIVE: To analyze risk factors for ectopic pregnancy (EP) after in vitro fertilization (IVF). DESIGN: A retrospective study of IVF pregnancies was performed between November 1983 and December 1989. SETTING: This study was conducted in a tertiary care center, the Port-Royal University Hospital. PATIENTS: Patients' records were reviewed for 48 EP and 508 intrauterine pregnancies obtained by IVF. INTERVENTIONS: Forty-six salpingectomies were performed for EP after IVF. MAIN OUTCOME MEASURE: We evaluated the impact on the ectopic rate of tubal status, the type of ovarian stimulation and luteal phase support, and the number of embryos transferred. RESULTS: Forty-three of 48 EP occurred in patients with tubal infertility. The rate of EP was significantly higher when the indication was tubal (11.1%) than when it was endometriosis (2.1%) or unexplained infertility (3.4%). Pathological findings revealed tubal lesions in all 46 salpingectomies. CONCLUSIONS: Ectopic pregnancy after IVF appears related to pre-existing tubal pathology. However, routine prophylactic salpingectomy to prevent the risk of EP does not appear justified. PMID- 1915944 TI - Tubal ectopic pregnancy after in vitro fertilization and embryo transfer: a role for proximal occlusion or salpingectomy after failed distal tubal surgery? AB - OBJECTIVE: To assess predisposing factors to tubal pregnancy after in vitro fertilization-embryo transfer (IVF-ET). DESIGN: Retrospective analysis of 891 ET cycles. SETTING: University-based IVF program. PATIENTS, PARTICIPANTS: All ET cycles performed in the study period were included; the indication for IVF was tubal factor in 640 (72%) and other (nontubal) factors in 251 (28%) cycles. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Observing a higher than expected number of tubal pregnancies in our program; we examined subgroups to determine those at highest risk. RESULTS: Tubal pregnancies comprised 12% of clinical pregnancies in the tubal factor group but only 2.6% in the cycles nontubal factor group (P less than 0.05). Of 640 ET cycles in the tubal factor group, 359 were performed in patients who had prior tubal reconstructive surgery; tubal pregnancies comprised 15.6% of the clinical gestations in this subgroup. In the remainder of the tubal factor group (no prior tubal surgery), 281 ET cycles yielded a tubal pregnancy rate of only 5.5% (P less than 0.05). CONCLUSIONS: Women with prior reconstructive surgery for distal tubal disease are at highest risk of developing tubal pregnancy after IVF. PMID- 1915945 TI - Partial zona dissection or subzonal sperm insertion: microsurgical fertilization alternatives based on evaluation of sperm and embryo morphology. AB - OBJECTIVE: To establish guidelines for application of partial zona dissection, subzonal sperm insertion, and regular in vitro fertilization (IVF) in severe male factor patients. DESIGN: Two studies were performed: partial zona dissection and IVF was applied in 57 couples during the first period, and subzonal sperm insertion was also applied in a second group of 47 couples. SETTING: Procedures were performed in an academic research environment. PATIENTS, PARTICIPANTS: Couples who failed fertilization previously, others not acceptable for IVF, and a third group in whom IVF was expected to fail. INTERVENTIONS: Oocytes were micromanipulated with either partial zona dissection or subzonal sperm insertion, or the zona pellucida was left intact. Embryos were replaced in patients prophylactically treated with methylprednisolone and antibiotics. MAIN OUTCOME MEASURES: Because several microsurgical fertilization techniques are now available, this study was performed to compare sperm parameters, embryo morphology, fertilization, and implantation rates after application of two successful micromanipulation procedures. RESULTS: Twenty-one pregnancies were established in 104 patients, 5 definitely from subzonal sperm insertion and 4 from partial zona dissection. Patients who failed IVF before had a similar chance of pregnancy after the use of micromanipulation, as first time patients (9/53 versus 12/51). In a subgroup of 15 patients who failed IVF with insufficient numbers of motile sperm, fertilization was significantly higher after subzonal sperm insertion. Partially zona-dissected embryos from couples with severe teratozoospermia (less than or equal to 5% normal forms; strict criteria) had significantly more morphological abnormalities than those from patients with moderate teratozoospermia (6% to 10% normal forms). In severely teratozoospermic patients, significantly fewer partially zona-dissected than subzonally inserted embryos implanted. CONCLUSIONS: The decision of which micromanipulation method to perform can possibly be based on careful analysis of sperm morphology. PMID- 1915946 TI - The effect of embryo quality on subsequent pregnancy rates after in vitro fertilization. AB - OBJECTIVE: To determine if a simple morphological classification of embryos was predictive of subsequent pregnancy. DESIGN: Prospective case series. SETTING: University-based in vitro fertilization (IVF) program. PATIENTS, PARTICIPANTS: Consecutive embryo transfer (ET) cycles (n = 206). INTERVENTIONS: Embryos were classified into three grades: (1) equal-size blastomeres with no fragmentation; (2) unequal-size blastomeres; and (3) evidence of fragmentation. MAIN OUTCOME MEASURES: Embryo quality, age, indication for IVF, and stimulation protocol were evaluated for their effect on pregnancy rates (PR's). RESULTS: In cycles in which the best embryo transferred was grade 3, 2, or 1, the clinical PRs per ET were 0% (0/11 cycles), 12.8% (6/47 cycles, P less than 0.05), and 21.8% (32/148 cycles, P less than 0.05), respectively. When one, two, or three or more grade 1 embryos were replaced, the clinical PRs per ET were 15.6%, 16.3%, and 40% (P less than 0.05), respectively. Using logistic regression, embryo quality (P = 0.0011) and patient's age (P = 0.0044) were the only variables that affected PRs. CONCLUSION: The transfer of more than two good quality embryos had a positive effect, patient's age had a negative effect on PRs after IVF-ET. PMID- 1915947 TI - The gonadotropin-releasing hormone agonist stimulation test--a sensitive predictor of performance in the flare-up in vitro fertilization cycle. AB - OBJECTIVE: To evaluate the initial versus early pattern of estradiol (E2) change after administration of a gonadotropin-releasing hormone agonist (GnRH-a), i.e., the GnRH-a stimulation test versus E2 pattern, respectively, as predictors of ovarian response and pregnancy in in vitro fertilization (IVF) patients stimulated with a flare-up protocol. DESIGN: Prospective study in a consecutive group of patients. SETTING: Tertiary care, institutional setting. PATIENTS: Two hundred twenty-eight patients entered and completed the study. The only patients excluded from study were those anticipated to have polycystic ovarian disease, those with a single ovary, or those with an ovarian cyst(s). INTERVENTIONS: Patients were stimulated with a GnRH-a flare-up protocol beginning on menstrual day 2. MAIN OUTCOME: Evaluation of the GnRH-a stimulation test and the E2 pattern as predictors of the number of mature oocytes retrieved and pregnancy. RESULTS: The GnRH-a stimulation test but not the E2 pattern was predictive of the number of mature oocytes retrieved (r = 0.53, P less than 1 X 10(-5) and pregnancy (chi 2 = 8.5, P = 0.04). The E2 pattern was predictive of the duration and number of ampules of gonadotropin required for stimulation. CONCLUSION: The GnRH-a stimulation test is a sensitive predictor of performance in the flare-up IVF cycle. PMID- 1915949 TI - Ejaculatory duct obstruction in subfertile males: analysis of 87 patients. AB - OBJECTIVE: To study the causes, presentation, and treatment of ejaculatory duct obstruction in subfertile males. DESIGN: Collaborative retrospective study of clinical experience collected by two urologists over a 15-year period. SETTING: National Health Service and Private Care Hospitals. PATIENTS, PARTICIPANTS: Subfertile males with azoospermia (n = 67), very severe oligozoospermia (n = 17), oligozoospermia (n = 1), or normal sperm concentration (n = 2) in small volume ejaculates with acid pH and little or no fructose. INTERVENTIONS: Exploration of scrotum with vasogram and testicular biopsy, plus reconstruction if possible. MAIN OUTCOME MEASURES: Follow-up seminal analysis and occurrence of pregnancy in female partners. RESULTS: The causes were: mullerian duct cyst (n = 17); wolffian duct malformation (n = 19); previous surgical trauma (e.g., imperforate anus) (n = 15); previous genital infection (n = 19); tuberculosis (n = 8); megavesicles (pathological dilatation of vesicles and ampullae of unknown cause) (n = 8); and carcinoma of prostate (n = 1). After incision of Mullerian duct cysts, five pregnancies were produced. Five pregnancies occurred in the other groups using a variety of surgical techniques. CONCLUSIONS: Routine vasography has shown that ejaculatory duct obstruction is not as rare as previously thought. The diagnosis should not be missed because the condition is simple to correct surgically in certain cases. PMID- 1915948 TI - The relationship between in vitro fertilization and naturally occurring antibodies: evidence for increased production of antiphospholipid autoantibodies. AB - OBJECTIVE: Assessment of possible effects of ovarian stimulation during in vitro fertilization (IVF) treatment cycles on circulating levels of antiphospholipid and antinuclear autoantibodies. DESIGN: The study was performed prospectively. Sera were obtained at three time points along IVF treatment cycle. Levels of autoantibodies directed against nuclear components, mitochondrial antigens, and phospholipids were determined using enzyme-linked immunosorbent assay. PATIENTS: Thirty-five patients, who underwent at least one previous IVF attempt, and 36 age and sex-matched controls were analyzed. All participants were randomly selected. RESULTS: The mean levels of antiphospholipid (but not antinuclear) autoantibodies in sera from IVF-treated patients were found to be significantly higher than the corresponding values of the control group (for immunoglobulin [Ig]M isotype: anticardiolipin, antiphosphatidyl L-serine; for IgG isotype: anticardiolipin, antiphosphatidyl L-serine, and antiphosphatidylcholine; P less than 0.0001, assessed by Mann-Whitney test). The autoantibody levels remained more or less constant at different time points along the treatment cycle. No correlation with age and number of previous IVF cycles was demonstrated. CONCLUSIONS: Serum levels of antiphospholipid (but not antinuclear) autoantibodies increase after IVF treatment. Based on these preliminary data, it is not yet possible to estimate if the observed changes in autoantibody levels might have any future clinical influence on infertile patients undergoing IVF treatment. PMID- 1915950 TI - Testis volumes, semen quality, and hormonal patterns in adolescents with and without a varicocele. AB - OBJECTIVE: To study the effects of varicocele on testicular function in adolescents. DESIGN: A prospective controlled study in 88 randomly selected adolescents. SETTING: All participants were referred to the fertility outpatient clinic of our University Hospital. PARTICIPANTS: All participants with a grade II varicocele (group 2) or a grade III varicocele (group 3) were selected at a district military medical council, whereas a similar group of healthy volunteers without a varicocele served as controls (group 3). INTERVENTIONS: Testis volumes were measured using an orchiometer. Semen analysis was performed according to standard procedures, and serum hormone levels were determined using a radioimmunoassay. MAIN OUTCOME MEASURE(S): Testis volumes, semen quality, and hormonal parameters in adolescents with and without a varicocele were compared. RESULTS: In group 1 (n = 21), the mean left testis volume (24.5 mL; 95% confidence interval [CI]: 22.8 to 26.2) was significantly (P less than 0.05) different from group 2 (n = 15) (20.9 mL: 95% CI: 18.5 to 23.4) and group 3 (n = 52) (20.7 mL; 95% CI: 19.2 to 22.2) (P less than 0.01) adolescents. In adolescents with a pronounced varicocele-associated left testicular growth failure, the total sperm number was reduced. However, sperm concentration, motility, and morphology were not altered. Luteinizing hormone, follicle stimulating hormone, testosterone, and prolactin levels were all within the normal ranges in the three groups. CONCLUSIONS: Left testicular growth failure in adolescents with a varicocele is only associated with a decrease in total sperm number. PMID- 1915951 TI - Human spermatozoa selection in improved discontinuous Percoll gradients. AB - OBJECTIVE: Improve the technique of human spermatozoa separation using Percoll density gradients. DESIGN: We compared the spermatozoa separation obtained after density gradients from a physiological stock Percoll solution and a hyperosmotic stock Percoll solution. SETTING: Sperm samples were obtained from the Laboratory of the Biology of Reproduction at Brest, France, a public hospital. PATIENTS, PARTICIPANTS: One hundred thirty-eight healthy donors. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The resolution of the separation was assessed by the number of motile spermatozoa recovered after separation using density gradients. RESULTS: The improvement of the resolution of separation is at least twofold greater with the use of hyperosmotic gradients than with that obtained by physiological gradients. Moreover, the best resolutions of separation were obtained from pathological sperm. Finally, the influence of buoyant density spermatozoa on the resolution of separation by this technique is clearly demonstrated. CONCLUSIONS: With this modification, the technique of Percoll density gradients, used for the separation of human spermatozoa, is strongly advised especially in pathological cases. PMID- 1915952 TI - The resazurin reduction test provides an assessment of sperm activity. AB - OBJECTIVE: The objective of the study was to determine if reduction of the dye resazurin by semen could be correlated with the concentration of motile sperm. DESIGN: After assessment of sperm count and motility, specimens were incubated for 1 hour with resazurin (25 micrograms/mL of semen) and visual color changes indicative of dye reduction noted. SETTING: Specimens were obtained from men seeking care for infertility at one of four sites: (1) University of California, San Francisco (UCSF) In Vitro Fertilization Program; (2) UCSF Andrology Laboratory; (3) a gynecological practice in Maine; and (4) a private andrology laboratory in Southern California. PATIENTS: Individuals were self-selected by their desire to have a semen analysis in conjunction with the diagnosis or treatment of infertility. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The reduction of the dye resazurin and its correlation with motile sperm density. RESULTS: When the motile sperm concentration was greater than or equal to 20 X 10(6)/mL, 86% of specimens produced a positive color change. Conversely, 86% of specimens with a motile sperm concentration of less than 20 X 10(6)/mL either did not change color or changed only over a narrow range. CONCLUSION: Reduction of resazurin offers an assessment of the active sperm in a specimen without the need to do a sperm count or evaluation of motility. PMID- 1915953 TI - Sperm donors: their attitudes toward providing medical and psychosocial information for recipient couples and donor offspring. AB - OBJECTIVES: To determine the willingness of sperm donors to provide in-depth medical and psychosocial information on their application forms and to share this information with recipient couples and their offspring. DESIGN: Sperm donors in two donor programs were asked to complete 12-page application forms. In addition to frequency tabulations of responses, chi 2 analyses were performed to compare responses from two programs. SETTING: The two donor programs were Baylor College of Medicine Sperm Bank Program, Scott Department of Urology, Houston, Texas, and Reproductive Resources, Metairie, Louisiana. MAIN OUTCOME MEASURES: Attitude toward providing in-depth medical and psychosocial information to recipient couples. RESULTS: Ninety percent of these donors are willing to complete lengthy application forms providing medical and psychosocial information. Ninety-six percent are willing to share this information in a nonidentifying manner with recipient families. Thirty-six percent say that they will be donors if anonymity cannot be guaranteed, and 60% indicate that they will meet or provide identifying information to the child at age 18. Seventy-two percent left personal messages to their potential offspring. CONCLUSIONS: Sperm donors are willing to provide in depth nonidentifying information for recipient families. Permanent files with medical and psychosocial information on all donors should be developed, maintained, and made available to all recipients, whether they request donor information at the time or conception or not. PMID- 1915954 TI - Reproductive hormone levels after pituitary allograft in cyclosporin-treated monkeys. AB - OBJECTIVE: To determine the course of events during the onset of hyperprolactinemic amenorrhea, a nonhuman primate model was sought that did not require suckling or interference with the in situ hypothalamic-pituitary axis. DESIGN: Because removal of the adenohypophysis from hypothalamic influence results in secretion of large quantities of prolactin (PRL) but little of the other adenohypophyseal hormones, we explored the possibility of establishing pituitary allografts in monkeys. Normally cycling female rhesus monkeys were immunosuppressed with a daily regimen of cyclosporin A (CyA; 10 to 15 mg/kg per day) and then subcutaneously grafted with a pituitary from another animal (allograft). Blood samples were obtained daily via saphenous vein puncture during control, only CyA-treatment, and allografted-plus CyA- menstrual cycles. SETTING: Oregon Regional Primate Research Center, Beaverton, Oregon. PARTICIPANTS: Female Macaca mulatta exhibiting regular menstruation. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prolactin, luteinizing hormone (LH), estradiol (E2), and progesterone (P) levels were determined in harvested serum. RESULTS: Temporary survival of 5 of 11 (45%) allografts was assumed based on elevations in serum PRL. Of the viable grafts, 4 of 5 (80%) resulted in reproductive dysfunction, as first evidenced by delay or loss of the preovulatory rise in E2. When the peak of follicular E2 was delayed, then the LH surge occurred, but it was also delayed. If follicular E2 levels did not peak, then the LH surge was absent as was luteal P production. CONCLUSION: These data suggest that in the etiology of PRL-induced infertility in women, the first event is a suppression of follicular E2 production. In addition, the hypothalamus probably remains responsive to the positive feedback of E2 during early or moderate hyperprolactinemia. PMID- 1915955 TI - Horse and marmoset monkey sperm bind to the zona pellucida of salt-stored human oocytes. AB - The present study demonstrates that horse and marmoset monkey sperm can bind to the human zona of salt-stored oocytes that failed to fertilize in vitro. Marmoset monkey sperm are also able to penetrate the salt-stored human zona. In contrast, human sperm do not bind to the zona of either horse or marmoset monkey oocytes. These results suggest that human sperm binding to the zona pellucida is more strictly species-specific than it is for horse and marmoset monkey sperm. In contrast, horse and marmoset monkey sperm contain receptors recognized by the human zona. PMID- 1915956 TI - Platelet-activating factor stimulates motion parameters of cryopreserved human sperm. AB - Platelet-activating factor is a naturally occurring molecule that does not appear to cause the detrimental effects to sperm as have been reported for other synthetic stimulatory agents. Incubation of freeze-thawed sperm with low motility with PAF at concentrations greater than or equal to 1.0 microM significantly improved a number of motion parameters (% motility, VSL and LIN). Optimal incubation conditions for PAF were defined at 1 hour and at 25 degrees C. The success of assisted reproductive techniques employing cryopreserved sperm with poor motility may be enhanced by stimulation protocols employing PAF. PMID- 1915958 TI - Uterine leiomyosarcoma with massive necrosis diagnosed during gonadotropin releasing hormone analog therapy for presumed uterine fibroid. AB - Recurrence of heavy vaginal bleeding and massive necrosis of a uterine leiomyosarcoma are reported in a 41-year-old female who was being treated with GnRH-a for a presumed uterine fibroid. The pathogenic mechanisms of such an event are reviewed and discussed in light of the available literature on the subject of GnRH-a and the treatment of uterine smooth muscle neoplasms. PMID- 1915957 TI - The detection of spermine and spermidine in human in vitro fertilization supernatants and their relation to early embryo-associated suppressor activity. AB - Suppressor activity in human IVF supernatants is dependent on the activity of monoamine oxidase present in nonheat-treated FBS and is therefore likely a polyamine. Pooled suppressive growth phase IVF supernatants were concentrated and subjected to HPLC fractionation. The inhibitory peak in the 1,000 to 2,000 d range was neutralized by antibody reactive with spermine and spermidine, and the presence of both polyamines was confirmed by TLC and by ELISA. These data suggest that IVF supernatant polyamines (spermine and spermidine) are responsible for the early embryo-associated suppressor activity correlating with pregnancy success. PMID- 1915959 TI - A 10-year prospective study of women with a history of recurrent fetal losses fails to identify Listeria monocytogenes in the genital tract. AB - An attempt was made to isolate L. monocytogenes from the cervix and endometrium of patients who presented to the Dartmouth-Hitchcock Medical Center's Reproductive Counseling Unit with a history of two or more fetal losses. Endometrial tissue and endocervical swabs were cultured in a prospective fashion for the presence of L. monocytogenes. During the 10-year study period, none of the patients with recurrent fetal losses were found to harbor the organism in their genital tract. It would appear that L. monocytogenes contributes to fetal loss, but probably not on a recurrent basis. Routine culturing for L. monocytogenes in the asymptomatic patient in a clinical setting is not cost effective and is therefore unwarranted. The portal of entry is possibly the GI tract, with bacteremia and transplacental spread to the fetus. Ascending infection through the introduction of L. monocytogenes into the vagina and cervix may occur. Because of the difficulty in identifying L. monocytogenes in the feces, as well as the self-limiting nature of listeriosis, it would appear unwarranted to give routine administration of antibiotics in patients who have had a history of a fetal loss because of L. monocytogenes. PMID- 1915960 TI - Slow excretion of exogenous human chorionic gonadotropin simulating repeated pregnancies and pregnancy losses. AB - We report a patient undergoing hMG-induced superovulation who demonstrated delayed excretion of hCG, originally believed to be because of successive biochemical pregnancies. However, sequential hCG titers after administration of exogenous hCG demonstrated a longer than normal half-life for the excretion of hCG in this patient. To what extent delayed excretion of hCG contributes to the diagnosis of biochemical pregnancy in assisted reproductive technology programs has yet to be determined. PMID- 1915961 TI - Influence of cigarette smoking on pituitary and sex hormone balance in healthy premenopausal women. AB - Plasma gonadotropin FSH and LH, PRL, sex steroids (17-beta E2, E1, and P), SBP binding capacity, and urine estrogens (E1, E2, and E3) were measured in 485 premenopausal healthy women, subdivided according to smoking habits. The aim of the study was to verify if cigarette smoking influences sex hormone balance. Baseline PRL levels were significantly lower (P less than 0.002) in smoker (n = 174) than in nonsmoker (n = 311) women. No difference was found in the other parameters of the two groups, particularly in plasma and urine estrogenic pattern. Our data suggest that smoking directly affects PRL levels by involving the hypothalamic mechanism that regulates PRL secretion. PMID- 1915962 TI - [Dental rehabilitation in the mentally retarded performed under general anesthesia]. AB - Experiences of dental treatments carried out in general anesthetization at the Oral Surgery and Dental Clinic between 1980 and 89. The 372 intravenous and 49 intratracheal narcoses and treatments are of "team" work characteristic and invite a better organization of the dental treatment of the mentally deficient. PMID- 1915963 TI - [Testing of dental enamel hardness by an in vivo method]. AB - The authors studied the microhardness of sound enamel in healthy persons, with in vivo measurements by the Vickersdiamond, used in earlier tests. The evaluation of the impressions was done by a modificated image-analysis method. The method by Fosse et al, for in vivo microhardness measurements can bring good results in practice according to the investigations. The image-analysis makes the evaluation essentially easier. The intraindividual use of this method in longitudinal examinations eliminates the sources of error occurring at horizontal comparisons. PMID- 1915964 TI - [Bacterial resistance of certain photopolymerizing filling materials and glass ionomer cements]. AB - In the course of the study the photopolimerizating filling materials (Visiomolar, Heliomolar, Heliosit, Silux, P-50, Prismatic) and the glass ionomer cements (Ketacfil, Ketac-silver) served as supposed sources of carbon for Ps. aeruginosa. All the examined materials have shown a suitable resistance to the studied bacterium species. If sunflower oil has been absorbed onto the surface of the examined materials, then a limited increase of the living germ counts has been observed. Ketac-silver was proved to be bactericidal in every case. PMID- 1915965 TI - [Survey of reasons for tooth extraction in the framework of government-sponsored dentistry]. AB - The purpose of this study was to determine the reasons for tooth extraction and to estimate the state of dental health in Hungary. Questionnaires with detailed instructions were sent to 300 Hungarian dental practitioners selected at random asking them to record and submit data on every extracted tooth during one month in 1986. They were also asked to give the reason for extraction in each case. 115 dentists returned completed forms on 7978 teeth which they had extracted. The dental caries was the most frequent cause for extraction (64%), followed by periodontal diseases (25.1%). 3103 teeth, 60.73% of teeth extracted because of caries had not been treated before the extraction. The results show that the dental caries remains the most important challenge for the Hungarian dental service during the next decades. The great numbers of extractions per dentist reveal the inadequacy of dental service in Hungary. PMID- 1915966 TI - [Caries epidemiology in Budapest nursery schools]. AB - The examination sample was a group of 1592 children of 3 to 6 years of age (787 boys and 805 girls). Aim of the examination was to gather information about the rate and intensity of caries cases of Capital kindergartners. The results permit to state that the rate and intensity of caries show a declining tendency in the last twenty years. Unfortunately, the ratio of children with front teeth caries increase. 39.4% of the 5 years old and 38.6% of the 6 years old have intact teeth. PMID- 1915967 TI - [Synchronously occurring malignant melanoma and gingival carcinoma]. PMID- 1915969 TI - [General principles of planning fixed prostheses on implants]. AB - The planning of fixed prostheses comprising also implant abutment is determined by that, as regards loadability, none of the implant kinds can be considered as first rate abutment tooth. At planning bridges the procedure according to the prosthetic principles related to weaker or damaged periodontium teeth is employed. PMID- 1915968 TI - [Study of the effectiveness of amine fluoride and stannous fluoride containing toothpaste and mouthwash]. AB - AmF and SnF2 containing toothpastes (equally 750 ppm F-) and mouthrinses (equally 125 ppm F-) from the GABA International Agency were tested. After a five month treatment period (daily two times tooth cleaning), in the saliva of the examined persons the germ counts of the S. mutans and Lactobacillus showed a decreasing tendency, though the change was not statistically significant. The control group used NaF containing cleaners (toothpaste; 1500 ppm F-, mouthrinse; 250 ppm F-) for also a five month treatment period. Within this group the germ counts of the microorganisms of the examined saliva did not change markedly. PMID- 1915970 TI - [The effect of toothbrushing on approximal dental surfaces]. AB - Altogether 52 teeth (20 anteriors, 13 premolars and 19 molars) scheduled for extraction were used for study. Before extraction the teeth were brushed with a medium textured toothbrush applying the modified Bass method with five strokes of proximal cleaning. The lack of professional and proximal cleaning aids makes planimetrically. The following conclusions were drawn: 1. The usual five strokes with a toothbrush are not able to remove old plaque, therefore professional tooth cleaning is necessary. 2. After toothbrushing twice as much plaque remains on the proximal than on the buccal and lingual surfaces. This implies the necessity of proximal cleaning. The lack of professional and proximal cleaning aids makes the establishment of good oral hygiene illusorical. PMID- 1915972 TI - [Angle of inclination of the frontal surfaces in the axis of the lateral incisors and first lower premolars]. AB - The angular offset of the tooth bed extensions of the upper jawbone and the mandible were evaluated in case of 280 intact skulls processed according to anthropological aspects (of 137 male, 116 female and 27 undeterminable genous). The angle measurements were carried out by goniometer between the alveolar edge of the tooth bed extensions and the root peak part, in reletion to the vertical straight at right angle to the Frankfurt horizontal plane, in the axis I. 2 on the upper jawbone, in I.2 on the mandible and in P.1. No significant differences were found between the measures either of males and females or of the right and left side. The offset angle of the front surface of the tooth bed extension showed an average value of -12.1 degrees on the maxilla in the axis I.2, 6.1 degrees on the mandible in the axis I.2 and 2.9 degrees in the P.1 axis. The data should be used for planning enossal dental implants. PMID- 1915971 TI - [5-year results of combines (radiation and surgical) treatment of intraoral squamous cell carcinoma]. AB - Results of the combined (irradiation + surgical) treatment of 33 patients, in great majority with advanced mouth cavity flattened epithelium are reported on. With 45% of the patients a 3 years survival could be obtained. The mainly radical surgical interventions were carried out after big dose preoperative irradiation treatment (Co. 60). PMID- 1915973 TI - [Classification of numerical anomalies of the dentition. Dental anomalies from the case load of a district dentist, 8]. PMID- 1915974 TI - [Abnormal production of adrenal gland hormones--special reference to mineralocorticoids]. PMID- 1915975 TI - [Abnormal production of adrenal gland hormones--special reference to glucocorticoids]. PMID- 1915976 TI - [Abnormal production of adrenal gland hormones--special reference to congenital adrenal hyperplasia]. PMID- 1915977 TI - Medical complications of pregnancy. PMID- 1915978 TI - Menstrual migraine. PMID- 1915979 TI - Nocturnal negative pressure ventilation. AB - In this study, 25 patients between the ages of 12 and 24 years who had neuromuscular diseases, a vital capacity less than 50 percent of predicted, and a history suggestive of nocturnal hypoventilation were observed with overnight monitoring of end-tidal CO2 (EtCO2) and O2 saturation (SaO2). Those patients with a strong clinical history and evidence of nocturnal hypoventilation (increased EtCO2 of 50 to 70 torr and decreased SaO2 [less than 90 percent]) (10 patients) were placed on nocturnal negative pressure ventilation (NNPV). Admission, treatment, and posttreatment arterial blood gases were analyzed by paired statistical "t" tests. Comparison of mean PaO2 values obtained on admission with those obtained during treatment revealed a greater than 97.5 percent confidence (p = 0.025; n = 7). Mean PaO2 values obtained after treatment (off negative pressure ventilation [NPV], awake during daytime) were 65.9 +/- 18.2 mmHg and 79.0 + 14.5 mmHg, respectively (p = 0.005; n = 6). Comparison of post-treatment PaO2 values as a percentage of admission (pretest) values showed a significant change at the 0.5 percent level with an applied Wilcoxan Signed-ranks Matched pairs Test. The mean PaCO2 values obtained upon admission and those obtained during treatment were 53.7 +/- 15.1 mmHg and 48.1 +/- 14.2 mmHg, respectively (p = 0.05; n = 7), and comparison mean PaCO2 values obtained upon admission and after treatment were 57.9 +/- 16.0 mmHg and 51.2 +/- 7.0 mmHg, respectively (p = 0.1; n = 6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915980 TI - Antimalarial effect of cyclosporin-A on murine P. berghei and human P. falciparum. AB - The effects of Cyclosporin-A (CsA) on the growth of Plasmodia were investigated in an experimental murine model in vivo and on human malaria in vitro. Mice were inoculated with Plasmodium berghei and then treated with different doses of CsA at the patent period. The development and course of this normally lethal parasitaemia in mice was affected by treatment with CsA which is a known immunosuppressant. The drug showed complete protection at a dose of 20 mg/kg wt/day without any recrudescence. Antibody level was at the detection limit after first bout of drug-cured infection. CsA was found to be an inhibitor of P. falciparum growth in a dose dependent fashion, as the concentrations of drug in culture medium increased, a significant reduction in parasitaemia was observed. PMID- 1915981 TI - Bionomics of Anopheles culicifacies giles in riverine tract rural areas of district Shahjahanpur, Uttar Pradesh. AB - Studies on seasonal prevalence, resting behaviour, gonotropic conditions and breeding habits of Anopheles culicifacies were carried out from January 1987 to December 1989 in riverine villages of Dadraul PHC in Shahjahanpur district, Uttar Pradesh. Man hour densities of An. culicifacies varied from 11.3 to 125.1 during the study period. The species showed two peaks of high prevalence: one during March to June and the other during October to December. The first peak was higher than the second. The collection revealed a higher proportion of freshly fed to semi-gravid females thus indicating the outdoor resting behaviour of the species. From the immatures collected from riverbed pools, 7 anopheline species were identified. Of the 955 specimens identified, An. culicifacies constituted the highest number (62.1%). The study indicates that low rainfall and drought did not affect An. culicifacies densities or malaria transmission in riverine areas. PMID- 1915982 TI - Living conditions and occurrence of malaria in a rural community. AB - Results of a prospective study of the association between environmental factors and malaria occurrence among 1461 individuals in an Indian rural community are reported. A multiplicative model was fitted by relating malaria positivity with different environmental risk factors as categorical variables. The risk of acquiring malaria infections varied significantly within a village stratified by proximity of breeding sources to human dwellings (chi 2 = 19.87, df = 5, p = 0.0000) and different types of houses (chi 2 = 11.32, df = 2, p = 0.0035). People residing in thatched houses with [Relative Risk (RR) = 6.72] and without false ceiling (RR = 11.27) are exposed to greater risk of contracting malaria infections when compared to tiled houses (RR = 1.00). However, malaria infection was not significantly associated with proximity of cattlesheds to human dwellings (chi 2 = 1.54, df = 2, p = 0.46). A significantly high risk was observed in zones where the cattle to man ratio was very low and vice versa (chi 2 = 15.32, df = 6, p = 0.018). These data suggest and corroborate with earlier studies that transmission is a local problem and it varies within a village according to the microepidemiological factors. PMID- 1915983 TI - Evaluation of juvenile hormone analogue JHM/S-31183 against immature stages of mosquitoes in natural habitats. AB - A study was carried out to evaluate the potentiality of Juvenile hormone compound JHM/S-31183 against immatures of mosquitoes in natural habitats. Of two formulations tested 1% emulsifiable formulation was marginally superior than the granule formulation. Adult emergence of An. stephensi was completely inhibited upto 12 weeks when 0.5% granule formulation was applied at 0.04 ppm in wells as against 50% inhibition upto 8 weeks in pools. However, in Culex quinquefasciatus the per cent inhibition of adult emergence varied from 52 to 90 per cent. 100% inhibition in pools upto one week at 0.04 ppm in An. stephensi was also obtained with 1% emulsifiable formulation but the effect was diluted in successive weeks. The impact of this formulation was not much pronounced against Culex quinquefasciatus. PMID- 1915985 TI - Insecticide susceptibility of mosquito vectors in Sundargarh district, Orissa. PMID- 1915984 TI - Symptomatic diagnosis of Plasmodium falciparum malaria in field conditions. AB - This paper examines the relationship between clinical manifestations and parasitaemia in relation to malaria endemicity. Discriminant analysis, showed that fever alone can detect 74.4% of the parasite positive cases and the inclusion of other symptoms like headache, vomiting, nausea, bodyache and diarrhoea marginally increases the efficiency of discrimination (i.e., from 74.4% to 74.7%). It was observed that the association of symptoms with parasitaemia varies with the degree of malaria endemicity. The percentage of correct classification of parasite carriers varied from 45.7% in the immune population to 80.6% in the non-immune population. A significant difference was observed in the density grades between symptom positive and symptom negative cases. Slide examination in hyperendemic area does not give any advantage over the clinical examination and the data obtained from the slides collected during fever surveys tend to overestimate the malaria incidence in hyperendemic area. PMID- 1915986 TI - Impact of monitoring on malaria control activities of PHC workers. PMID- 1915987 TI - Seasonal prevalence of anophelines in Kheda district, Gujarat. AB - Seasonal changes in the population structure of anophelines were studied in Kheda district, Gujarat. Mosquito collections were made from the villages of Nadiad taluka, representing 3 different physiographic zones. Maximum number of anopheline species (13) were recorded from canal irrigated area followed by 11 species from non-canal irrigated and 8 species from riverine areas. Four anophelines namely An. subpictus, An. culicifacies, An. annularis and An. stephensi were predominant. High densities of An. culicifacies and An. subpictus were recorded in March and August. Results of a four year study (1985 to 1988) on the population of anophelines from 3 different physiographic entities showed marked differences in the seasonal abundance of different species. PMID- 1915988 TI - Dental implants. PMID- 1915989 TI - The epithelial interface with osseointegrated implants. AB - The development of osseointegration has generated interest in the field of intraoral and maxillofacial implantology. There is well documented evidence of a high level of success in achieving osseointegration, using titanium and alumina ceramic implant materials. Long term retention of intraoral implants appears in part, to be dependent upon the integrity of the epithelium/implant interface. This paper presents the design features of two commercially available systems Intra-Mobile-Zylinder (IMZ) and Tubingen (Frialit), which represent titanium and alumina-ceramic implants respectively, and reviews current knowledge of the nature of the epithelial junction to implant materials and the bacterial flora associated with successful and failing implants. Implant failure may be caused by a site specific infection with a similar ecosystem and bacterial flora to that found in periodontal disease. Care in patient selection and maintenance of a healthy epithelial junction are essential for the long term function of osseointegrated implants. PMID- 1915990 TI - Anterior veneers for the adolescent patient: 1. General indications and composite veneers. AB - Composite and porcelain veneers offer a conservative method of masking discolouration of the teeth of younger patients. Composite veneers are the less destructive of tooth tissue, but also the less durable. This two-part article reviews the use of veneers in treating the adolescent patient. Part 1 examines indications for treatment and gives a step-by-step guide to the clinical procedure for veneering with composite. Next month, Part 2 will cover porcelain veneers and draw some overall conclusions. PMID- 1915991 TI - Stress in dental practice. AB - The life of a GDP is stressful, and the reasons why dentists may experience stress in their chosen profession are many and varied. This article discusses the causes of stress, and outlines some strategies for coping with it. PMID- 1915992 TI - The history, development and use of interproximal wedges in clinical practice. AB - Wedges, when correctly selected and applied, can make an important contribution to the initial quality and the longevity of some restorations, and can greatly facilittae a number of clinical procedures. The authors outline the important role of interproximal wedges in restorative dentistry, and, in an historical perspective, describe how the principles elucidated when wedges were first employed in restorative dentistry more than 150 years ago are still applicable today. PMID- 1915993 TI - Functional appliances: a systematic approach. AB - It can be argued that all functional appliances are basically similar, using a family of common component parts. The components incorporated into a design should be chosen rationally, after consideration of the particular malocclusion to be treated. This article therefore explains functional appliances in terms of their components. It aims to give a greater understanding of the principles involved, and thus aid the practitioner in prescribing the most appropriate design for a particular clinical situation. PMID- 1915994 TI - Transposition. PMID- 1915995 TI - Amelogenesis imperfecta: early interception to prevent attrition. AB - Early recognition and action are essential elements in the management of amelogenesis imperfecta. The authors describe how a combination of prompt clinical action and preventive care were used to minimize the chances of decay and wear to the permanent dentition of a young patient suffering from this condition. PMID- 1915996 TI - [Insulin analogs in 1991]. AB - Despite multiple injections of soluble insulin, it remains impossible to perfectly simulate physiological post-prandial plasma insulin profile. Moreover, crystal suspensions of very long-acting insulin show wide variations in the kinetics of crystal dissolving and therefore in biological activity. These data have lead to the development of insulin analogues, either very rapid-acting or long-acting, in order to avoid these disadvantages. This study focuses on the in vitro characteristics, the biological effects in animals, and the clinical effects in healthy subjects and in diabetic patients of the analogues having therapeutic potential. PMID- 1915997 TI - [Insulin secretion in nondiabetic manioc consumers]. AB - The study of pancreatic beta cell function during an intravenous glucose tolerance test performed on 28 healthy cassava eaters showed 3 types of response: normal insulin secretion in 17 subjects, a significantly elevated peak at 30 min, compared to the control group (6 subjects p less than 0.0125), with preservation of insulin secretion dynamics, and a late peak at 120 min. (5 subjects p less than 0.0125). Among the different factors capable of stimulating insulin secretion, in absence of a significant increase in glycaemia, the hypothesis of cell membrane lesions caused by cyanogenic components has been suggested. The abnormalities observed seem to be in relation with the length of duration of cassava consumption, but neither with plasmatic or urinary levels of thiocyanate, nor with the genetic study. PMID- 1915998 TI - Effect of weight loss on insulin sensitivity and cardiovascular risk factors in glucose tolerant and intolerant obese subjects. AB - We observed 170 obese patients during 55 weeks in order to study the influence of insulin resistance and insulin sensitivity on cardiovascular risk factors in such patients as well as the changes occurring on these subjects as a result of weight loss. At the beginning of the study, the patients were divided into two groups, according to the results of an oral glucose tolerance test (OGTT) performed with 75 g of glucose: Group A, glucose tolerant subjects (n = 81), Group B, glucose intolerant subjects (n = 89). Initially Group B patients showed higher values for fasting blood glucose, 2 h after OGTT, systolic and diastolic blood pressure, cholesterol, triglycerides and cholesterol/HDL-cholesterol ratio when compared to Group A patients (p less than 0.05). Fasting and 1 h-post glucose load serum insulin levels in both Group A and Group B patients were higher than those found out in non over-weight tolerant subjects, but there were no differences between both groups. The serum glucose descent slope after an insulin tolerance test (ITT) was lower for group B than for group A (p less than 0.05), whereas both groups demonstrated lower descent slopes than non overweight tolerant subjects (p less than 0.05). After a 55 weeks follow-up period, the patients in Group A had lost 4.6 +/- 0.7 kg and those in Group B 6.2 +/- 1.1 kg. In both groups, the values for SBP, DBP, FBG, triglycerides and cholesterol/HDL-cholesterol ratio had dropped significantly, with a rise in the HDL-cholesterol level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1915999 TI - Total and cause-specific mortality in a population based cohort of diabetics in Greece. AB - Eleven years after a diabetes detection drive--conducted in a sample of 21,410 individuals--a follow-up study showed that 207 persons had died from a total of 489 previously known diabetics. Ten year survival rates were lower in male and female diabetics as compared to those observed in the general population. In addition it was shown that diabetic patients died more often from cardiovascular causes compared to sex and age matched samples of the general population (males 63.3% vs 44.3%; females 76.0% vs 51.7%). No mortality differences by the type of hypoglycaemic treatment were noted. PMID- 1916000 TI - [Does glycemic level influence the pharmacokinetics of an antibiotic (cefoperazone)?]. AB - Hyperglycemia may modify pharmacokinetics of some antibiotics as shown in the literature. We studied the influence of glycaemic levels on pharmacokinetics properties of cefoperazone in 12 type 1 insulin dependent diabetic patients. Hyperglycaemia was obtained by a reduction of one quarter of their usual insulin dosage and normoglycaemia by an artificial pancreas (Biostator GCIIS). Cefoperazone had a high protein affinity and a high biliary elimination. Pharmacokinetic study was performed during a 8 hour period following one gram intravenous bolus. We did not found any influence of glycaemic level (normoglycaemia or hyperglycaemia) on the pharmacokinetic parameters of cefoperazone. PMID- 1916001 TI - The type 1 diabetes and HLA-DR in Turkey. AB - Studies of various insulin-dependent diabetes mellitus (IDDM) populations have shown that certain HLA antigens confer a high risk of developing disease. There is very little information concerning the distribution of HLA antigens in type 1 diabetes in the Turkish population. In this study, the HLA types of 75 patients and 50 controls were investigated. HLA-DR3 and HLA-DR4 were found more frequently in the IDDM cases (p = 0.0018 and 0.0119, respectively). DR3/DR4, although more frequent, did not achieve statistical significance. The decreased frequencies of DR1 and DR2 in the IDDM population were not significant whereas the DR7 was found to be significantly decreased (p = 0.025). The younger age of onset was strongly associated with DR4 (p = 0.0029). DR3 was more common among the male and DR4 in the female patients. However, the differences were not significant. PMID- 1916002 TI - [Is glycated hemoglobin always a reliable marker of long term metabolic control in diabetic patients?]. PMID- 1916003 TI - [Should one extend the indication for pancreas transplantation to non-uremic insulin dependent diabetic patients?]. PMID- 1916004 TI - Different patterns of inhibition of adrenaline-induced platelet aggregation and kinetics in vivo by acetylsalicylic acid and indobufen. AB - The inhibitory effect of 50 mg/kg lysyl acetylsalicylic acid (ASA) intravenously injected 24 and 4 h before 80 micrograms/kg adrenaline, 40 mg/kg indobufen injected 15 min before, or a combination of ASA plus indobufen on the platelet aggregation and kinetics was evaluated in anaesthetized dogs previously injected with 111indium- (111In-) labelled platelets using gamma-camera dynamics studies. The highest degree of inhibition, indicated by the lowest platelet aggregation ratio decrease and the most significant 111In-labelled platelet mobilization from hepatic and splenic stores with a corresponding increase of labelled and unlabelled platelet counts in blood, was obtained in ASA-treated dogs. Such changes were less marked when ASA plus indobufen was injected. In indobufen treated dogs a similar mobilization of 111In-labelled platelets with an increase in circulating platelet numbers was evident only after the second adrenaline injection. It is concluded that platelet mobilization is mainly dependent on the production of an ASA-sensitive substance. PMID- 1916005 TI - Chronic lisuride hydrogen maleate administration enhances muscarinic receptor binding in senescent rat brain. AB - Changes in the regional density of muscarinic-1 (M1) receptors and the effect of lisuride hydrogen maleate on these changes were studied in senescent rat brain by in vitro autoradiography. In young adult controls, M1 receptor binding was most dense in the striatum and hippocampus, followed by the cerebral cortex and amygdala. Binding to M1 receptors was markedly lower in these areas of the senescent brain compared with the young adult brain. These decreases were reversed by intraperitoneal administration of 50 micrograms/kg.day lisuride for 14 days. The present results indicate that the therapeutic efficacy of lisuride depends on normalization of not only monoamine systems but also acetylcholine systems. PMID- 1916006 TI - The effect of steroids on theophylline absorption. AB - The effect of hydrocortisone on plasma theophylline concentrations was evaluated in 20 patients suffering from chronic bronchitis or stable bronchial asthma. Choline theophyllinate (400 mg) was orally administered every 12 h for 8 days and blood samples were taken every 2 h during the day for the measurement of theophylline concentrations. Intravenous bolus injections of 500 or 1000 mg hydrocortisone on day 5 or day 7, respectively, did not significantly alter plasma theophylline concentrations. PMID- 1916007 TI - A multicentre trial to evaluate the efficacy and tolerability of alpha glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia. AB - An open clinical trial was carried out to compare the efficacy and the tolerability of 1 g/day alpha-glycerylphosphorylcholine (alpha-GPC) with 1 g/day cytosine diphosphocholine (CDP) both given intramuscularly for 90 days in 120 patients with mild to moderate vascular dementia. The clinical evaluation, carried out at the start as well as halfway through (45 days) and at the end of treatment (90 days), was expressed by psychometric tests (modified Parkside behaviour rating scale, Sandoz clinical assessment geriatric scale, word fluency test, Hamilton's rating scale of depression, narration subtest of Wechsler memory scale). Both treatments produced a definite symptomatic improvement and showed a very good tolerability. The results suggest that in most tests alpha-GPC possessed a statistical higher efficacy and an overall more satisfactory activity assessed by both patients and investigators compared with CDP. PMID- 1916008 TI - Circadian blood pressure rhythms in elderly hypertensive patients. AB - Blood pressure was recorded for 24 h in 121 essential hypertensive patients aged between 20 and 90 years. To characterize the circadian blood pressure rhythm, the differences between the daytime blood pressures (recorded at 8-min intervals between 8 a.m. and 10 p.m.) and the night-time blood pressures (recorded at 30 min intervals between 10 p.m. and 8 a.m.) were calculated. The difference between daytime and night-time blood pressures was significantly (P less than 0.01) decreased in elderly hypertensive patients aged between 65 and 90 years compared with in those aged 20-39 years. In patients with heart insufficiency the circadian blood pressure rhythmicity was significantly (P less than 0.05) further reduced compared with in uncomplicated hypertensives. This may be explained by increased sympathetic tonus in patients with heart insufficiency and reduced vascular compliance may be the cause of the overall reduced circadian blood pressure rhythmicity in elderly hypertensive patients. PMID- 1916009 TI - Complement activation via the alternative pathway in a patient with insulin dependent diabetes mellitus. AB - A 41-year old male with insulin-dependent diabetes mellitus previously unsuccessfully treated with a controlled diet and glibenclamide, and subsequently with increasing insulin doses (5 and 20 IU/day) experienced polyuria, glycosuria and loss of weight. On admittance to hospital serum C3 concentrations were found to be depressed. The insulin dose was further increased to 30 IU/day and the patient was also treated with 20 mg nafamostat mesylate given intravenously twice daily for 6 days. On completion of nafamostat mesylate treatment serum C3 concentrations were increased but after 17 days they started to decrease again. PMID- 1916010 TI - Syndecan, a cell surface proteoglycan, exhibits a molecular polymorphism during lung development. AB - Syndecan, a cell surface proteoglycan, binds multiple extracellular ligands, and is developmentally regulated in epithelial and mesenchymal tissues. The branching morphogenesis of embryonic lung is dependent on epithelial-mesenchymal interactions and, based on studies with inhibitors, on proteoglycan synthesis. To assess the role of syndecan in lung development, we examined the structure and distribution of syndecan in Day 12 to 18 embryonic mouse lungs using monoclonal antibody 281-2 for histology, immunopurification, and Western blots. At Day 12, syndecan localizes mainly on epithelial cell surfaces, but also stains mesenchymal cells near the epithelium. By Day 14, syndecan is expressed predominantly on epithelia and by Day 18, syndecan remains on airway epithelia but is absent from the alveolar pneumocytes. This change in expression correlates with a change in syndecan structure; the relative mass of syndecan gradually falls from Day 12 to Day 18 without a change in relative mass of the core protein. The difference is due to a developmental reduction in the size of the glycosaminoglycan chains; heparan sulfate chains on syndecan from Day 14 lungs were nearly twofold larger than those from Day 18 lungs. Newly synthesized syndecan in the lungs had the same relative mass as total syndecan, indicating that the change in mass is due to a developmental change in the nature of the syndecan synthesized. The alteration in syndecan structure could alter the function of this proteoglycan during lung development. PMID- 1916011 TI - A head signal influences apical migration of interstitial cells in Hydra vulgaris. AB - Although interstitial cells of hydra can migrate either apically or basally along the body column, there is a distinct bias toward apical cell accumulation. This apical bias could be produced by a local vectorial property of the tissue or it may be controlled by a more global property, such as a signal from the apical head region. The migration behavior of BrdU-labeled interstitial cells was examined in several types of grafts to distinguish between these two general types of migration control. Grafting BrdU-labeled midgastric region tissue into a host in either the normal or the reverse orientation had no effect on the apical bias, indicating that a local vectorial cue was probably not guiding cells apically. In grafts with heads or with feet at both ends of the body column, there was no directional bias in migration if the labeled tissue was equidistant from both ends. In the two-headed grafts, if the labeled tissue was closer to one end, there was a bias in the direction of the closer head. The results suggest that a graded signal emanating from the head creates the apical bias and may attract cells via chemotaxis. The apical bias is enhanced in decapitated animals regenerating a head, indicating that the attracting signal is present and is possibly stronger in regenerating heads. The signal for cell migration may be involved in a patterning process underlying head regeneration. PMID- 1916013 TI - Spindle pole centrosomes of sea urchin embryos are partially composed of material recruited from maternal stores. AB - The spindle poles of fertilized sea urchin eggs have commonly been modeled as being derived from the centrosomes of the fertilizing spermatozoon. Boveri's theory of fertilization, proposed at the turn of the century, states that the maternal centrosome is suppressed or inactivated during oogenesis and that the sperm centrosome is functionally dominant. In support of this proposal, more recent studies have shown that the sperm imports a determinant that is involved in centrosomal replication. Examination of sea urchin zygotes immunofluorescently labeled with a new anti-centrosomal antibody by quantitative confocal laser scanning microscopy shows, however, that spindle pole centrosomes are not exclusively paternal structures, but additionally contain material derived from maternal pools. Furthermore, this maternal centrosomal material is divided among daughter blastomeres during cleavage. It therefore appears that although the sperm centrosome plays a dominant role in organizing the spindle poles, much of the centrosomal material within the spindle poles of the zygote is actually recruited from preexisting egg cytoplasmic stores. These data indicate that centrosomes of sea urchin embryos are biparentally derived, composite organelles. PMID- 1916012 TI - Increased aggrecan (cartilage proteoglycan) production in the sclera of myopic chicks. AB - A previously characterized chick model of myopia was used to evaluate biochemical changes in the sclera which are associated with ocular enlargement and myopia. Chicks were monocularly occluded for 10 days and the DNA, hydroxyproline, and glycosaminoglycan contents of the sclera were compared between the normal and the myopic eyes. No significant differences could be detected in total DNA or hydroxyproline content. There was, however, a 34% increase in glycosaminoglycans and a 20.7% decrease in cell density within the posterior sclera of myopic eyes. The biosynthesis of scleral proteoglycans was determined by measuring 35SO4 incorporation in the sclera of chicks visually occluded for 5, 10, and 15 days. No differences could be detected in 35SO4 incorporation into the cornea or the anterior sclera. However, 35SO4 incorporation was significantly increased in the posterior sclera of myopic eyes by 64% at Day 5, 39% at Day 10, and 49% at Day 15. When fractionated on Sepharose CL-4B, scleral proteoglycans were resolved into two peaks which were identified by Western blot analysis as aggrecan (cartilage proteoglycan) and decorin. Furthermore, Western blot and dot blot analyses indicated that significantly more aggrecan core protein was present in the sclera of myopic eyes compared with equivalent amounts of sclera from control eyes. These results indicate that increased synthesis and accumulation of aggrecan, which increases the volume of extracellular matrix in the posterior sclera, are responsible for the ocular enlargement observed in this model of myopia. PMID- 1916014 TI - Furrow-related contractions are inhibited but furrow-unrelated contractions are not affected in af mutant eggs of Xenopus laevis. AB - In embryos from af mutant females of Xenopus laevis, the cleavage furrows stayed on the surface and cytoplasmic divisions did not take place at all, while nuclear divisions continued (Kubota et al., 1991). To gain insights into the roles of the normal product of af on early development, contractile events which have been observed in the period from fertilization until first cleavage in wild-type eggs were examined in af mutant eggs. Activation waves, activation contraction, and surface contraction waves which were identical to those in wild-type eggs were observed in af eggs by time-lapse video recording. However, second polar body elimination was inhibited in af eggs, although a sign of the polar body formation was indicated by the cytoplasmic bulge of the egg surface as seen by light and electron microscopy. These results indicate that the normal product of af regulates furrow-related contractile events which involve formation of the contractile ring, but exerts no effects on furrow-unrelated contractions in early Xenopus eggs. PMID- 1916015 TI - Axonal transport and release of transferrin in nerves of regenerating amphibian limbs. AB - Transferrin, a plasma protein required for proliferation of normal and malignant cells, is abundant in peripheral nerves of birds and mammals and becomes more concentrated in this tissue during nerve regeneration. We are testing the hypothesis that this factor is involved in the growth-promoting effect of nerves during the early, avascular phase of amphibian limb regeneration. A sensitive enzyme-linked immunosorbent assay for axolotl transferrin was developed and used to determine whether this protein meets certain criteria expected of the trophic factor(s) from nerves. During limb regeneration adult sciatic nerves greatly increased their content of transferrin, which immunohistochemistry revealed was distributed in both axons and Schwann cells. Using the double ligature method with sciatic nerves in vivo, it was determined that transferrin is carried by fast anterograde axonal transport at all stages of limb regeneration. An approach based on multicompartment organ culture demonstrated that fast-transported transferrin was secreted in physiologically significant amounts at distal ends of regenerating axons. Finally, the concentration of transferrin in the distal region of larval axolotl limb stumps was found to decrease directly and rapidly in response to axotomy. Since transferrin is important for both axonal regeneration and cell cycling, the present data have significance for various aspects of nerve's trophic activity during limb regeneration. PMID- 1916016 TI - Regulation of gene expression in preimplantation mouse embryos: effects of the zygotic clock and the first mitosis on promoter and enhancer activities. AB - Previous studies have reported that promoters requiring enhancers for full activity in mammalian somatic cells also require enhancers when injected into mouse two-cell embryos, whereas the same promoters can be expressed just as efficiently in the absence of an enhancer when injected into arrested one-cell embryos. Experiments were designed to determine whether this phenomenon reflected normal developmental changes at the beginning of mammalian development, or simply differences in the physiological states of these cells under the experimental conditions employed. The activity of three different promoters that function in a wide variety of mammalian cells was measured both in embryos whose morphological development was arrested and in embryos that continued development in vitro. Expression of the injected gene was related to the onset of zygotic gene expression ("zygotic clock"), the phase of the cell proliferation cycle, the use of aphidicolin to arrest cell proliferation, and formation of two-cell embryos in vitro and in vivo. The results demonstrated that promoter activity was tightly linked to zygotic gene expression, while the need for enhancers to stimulate promoter activity depended only on formation of a two-cell embryo. These results further support the hypothesis that the first mitosis induces a general repression of promoters prior to initiation of zygotic gene expression that is relieved specifically by enhancers. PMID- 1916017 TI - Aggregation of beta-1,4-galactosyltransferase on mouse sperm induces the acrosome reaction. AB - beta-1,4-Galactosyltransferase (GalTase) is present on the surface of mouse sperm, where it functions during fertilization by binding to oligosaccharide residues in the egg zona pellucida. The specific oligosaccharide substrates for sperm GalTase reside on the glycoprotein ZP3, which possesses both sperm-binding and acrosome reaction-inducing activity. A variety of reagents that perturb sperm GalTase activity inhibit sperm binding to the zona pellucida, including UDP galactose, N-acetylglucosamine, alpha-lactalbumin, and anti-GalTase Fab fragments. However, none of these reagents are able to cross-link GalTase within the membrane nor are they able to induce the acrosome reaction. On the other hand, intact anti-GalTase IgG blocks sperm-zona binding as well as induces the acrosome reaction. Anti-GalTase IgG induces the acrosome reaction by aggregating GalTase on the sperm plasma membrane, as shown by the inability of anti-Gal-Tase Fab fragments to induce the acrosome reaction unless cross-linked with goat anti rabbit IgG. These data suggest that zona pellucida oligosaccharides induce the acrosome reaction by clustering GalTase on the sperm surface. PMID- 1916018 TI - Stimulation of head-specific nerve cell formation in Hydra by pulses of diacylglycerol. AB - In Hydra magnipapillata, repeated pulses of diacylglycerol (DG) induce a lengthening of the body column and the formation of ectopic head structures (Muller, 1989). In the present study, seven pulses given on 7 successive days led, in the gastric region, to a 1.87-fold increase in the number of epithelial cells from 16,200 to 30,400; a 4.6-fold increase in the total number of nerve cells from 2900 to 13,400; and an 18-fold increase of RF-amide immunopositive nerve cells from 100 to 1800. This subset of neurons, which is normally distributed in the form of a density gradient having its high point around the mouth and ending below the tentacle whorl in the upper gastric column, displays an altered pattern in DG-treated animals. While the density peak in the original head persisted, a second peak developed in the lower gastric region at the site of imminent ectopic tentacle formation, reflecting the local increase in positional value. Thus, the temporal sequence in which DG-induced ectopic apical body structures arise is a function of the rise in positional value and reflects the normal spatial sequence of these structures along the body column: first RF amide neurons appear, then tentacles, and finally hypostomes. PMID- 1916019 TI - Synaptic differentiation can be evoked by polymer microbeads that mimic localized pericellular proteolysis by removing proteins from adjacent surfaces. AB - Synaptic differentiation is normally "induced" by regulatory signals that are exchanged only at close contacts between neurites and their predetermined target cells. These signals can, however, be mimicked by contact of either cell with some kinds of polymer microbeads. To find what bead action is responsible for this mimicry, we compared the effects of active and inert microbeads on Xenopus muscle cells developing in culture and on glass-adsorbed films of laminin or fibronectin. Our results show that inductive bioactivity is a property of native polystyrene microbeads that (a) is not dependent merely on bead-muscle adhesion, (b) can be eliminated simply by exposing the beads to inert serum proteins, and (c) correlates closely with the ability of some beads to desorb proteins from adjacent surfaces. Quasi-synaptic differentiation of the muscle surface thus seems to be triggered by the focal removal of peripheral cell surface components, rather than by direct bead interactions with membrane receptors or ion channels or their gradual acquisition of endogenous regulatory substances. Since nerve muscle interaction also causes an elimination of extracellular matrix proteins from the muscle surface, very early in synapse development, we consider the possibility that the extracellular degradation of peripheral surface components contributes to the transmission of inductive positional signals during synaptogenesis. PMID- 1916020 TI - Temporal pattern of posterior positional identity in mouse limb buds. AB - This study describes the temporal pattern of posterior positional identity in mouse limb bud cells. To do this wedges of tissue from the posterior edge of mouse limb buds at various stages (limb stages: Wanek et al., 1989b. J. Exp. Zool. 249, 41-49) were grafted to the anterior edge of a host chick embryo wing bud. Grafts of mouse posterior cells are able to induce the formation of supernumerary digits every time when they are taken from buds from stage 3 through stage 6. At stage 7, the frequency declines and by stage 8 the chick cells no longer respond. The results indicate a change in tissue properties at stage 7, which progresses by stage 8 to the point at which posterior positional identity is no longer detectable by this assay. These temporal changes in this aspect of limb pattern formation can be used as an additional criterion to guide the identification of genes involved in the specification of posterior positional identity. PMID- 1916022 TI - Basic co-ordination of manipulative forces of children with cerebral palsy. AB - The coordination of manipulatory forces during prehension was studied in 12 children with cerebral palsy (CP) and compared with that of controls. The results indicated that coupling of grip force and load force does not develop in children with CP. These children's force development increased in stages, with an early onset of excessive grip force. They did not use anticipatory control of the isometric force development during the load phase. Prolonged delays between successive phases indicated inefficient sensory feedback during the movement. The early onset of grip force and the over-all high force employment may compensate for the lack of anticipatory control and inefficient sensorimotor integration. PMID- 1916021 TI - EGF antisense oligodeoxynucleotides block murine odontogenesis in vitro. AB - The initiation of odontogenesis depends on the site-specific proliferation of mandibular epithelium beginning at Day 11 in embryonic mice. We have previously reported that the local expression of epidermal growth factor mRNA in the murine mandible is developmentally regulated, expressed at Days 9 and 10 immediately prior to the initiation of tooth bud formation at Day 11. Exposure of Day 9 mandibular explants to antisense oligomers of epidermal growth factor blocks the initiation of odontogenesis. These results are the first demonstration of the involvement of epidermal growth factor in the inductive specification of a complex epithelial derivative. PMID- 1916023 TI - Kinaesthetic abilities of clumsy children. AB - Kinaesthesis was examined in 80 clumsy and 80 control children aged between six and nine years. Seven tasks were administered which required passive and active movements in both kinaesthetic and kinaesthetic-visual modes. Clumsy children performed inferiorly on three tasks which involved passive or active demands. A range of tasks appears to be necessary to identify kinaesthetic dysfunction. PMID- 1916024 TI - Neuropsychological aspects of tuberous sclerosis in relation to epilepsy and MRI findings. AB - The neuropsychological performances, outcome of epilepsy and MRI topography of tubers of 23 children with tuberous sclerosis were reviewed. Seven children had normal intelligence, 10 had mental retardation, and six mental retardation and autism. An adverse association was found between the number of lesions and IQ, behaviour and severity of epilepsy. Posterior lesions, in addition to frontal lobe dysfunction, were observed in children with autism. Tuberous sclerosis with well-defined cerebral lesions may represent a model for the relationship between different neuropsychiatric problems. PMID- 1916025 TI - Behaviour of severely malnourished children in a Jamaican hospital. AB - The behaviour of 18 children with severe malnutrition between the ages of six and 24 months was observed. They were compared with 21 age-matched adequately nourished children in hospital with other diseases, and were given regular developmental assessments with the Griffiths test. On admission to hospital the malnourished children were less active and more apathetic than the controls when alone in their cots, while the controls were more distressed. When given toys, initially the malnourished children explored them less, using fewer play actions and touching fewer toys. These differences were not present on recovery. Initial behaviour did not predict later developmental levels. PMID- 1916026 TI - Prader-Willi syndrome in a Swedish rural county: epidemiological aspects. AB - The total population under 25 years of age in one rural county in Sweden was screened in an attempt to find all cases of Prader-Willi syndrome and to establish prevalence rates for the disorder. 11 clear and five suspect cases were found. For the seven- to 25-year-old age-group the prevalence was 13 per 100,000 for clear cases only, but 20 per 100,000 if borderline cases were included. There was a slight over-representation of males, but it was possible that this was a result of under-representation of females in the very young age-groups, in whom hypogonadism may be difficult to diagnose. PMID- 1916027 TI - Forced-choice preferential looking acuity of children with cortical visual impairment. AB - Forced-choice preferential-looking acuity estimates from cortically visually impaired (CVI) infants and children were compared with three measures of visual function. Mean acuity deficit varied with fixation, tracking and visual impairment. Acuity deficit correlated with centile score for sensorimotor skills, but not for gross motor skills. The results suggest that these estimates provide information about the CVI child's ability to use vision in everyday life. Correlations were found between initial acuity deficits and acuity deficits measured from three months to six years later. Forced-choice preferential-looking acuity estimates may be useful for evaluating treatment response and establishing guidelines for educational materials for these infants and children. PMID- 1916028 TI - Multiple minor malformations as a marker for prenatal etiology of cerebral palsy. AB - A consecutive series of 137 patients with cerebral palsy living in institutions and aged between 18 and 30 years was examined for minor malformations, using a modified Weighted Anomaly Score. After examination, the patients were divided into two groups, based on whether their cerebral palsy was prenatal or postnatal in onset. A further subset of prenatal-onset patients with unidentified etiology was also analysed. Both the prenatal group with known etiology and the subgroup with unknown etiology had significantly more minor malformations than the postnatal group. These results suggest that multiple minor malformations may indicate prenatal etiology of cerebral palsy. PMID- 1916029 TI - 'Idiopathic childhood absences', a system disorder: its diagnosis and differentiation. PMID- 1916030 TI - Low level of GABA in CSF in vitamin B6-dependent seizures. PMID- 1916031 TI - Dopa-responsive dystonia. PMID- 1916032 TI - BRL 24924, a 5-hydroxytryptamine type 3 antagonist, and gastric secretion of acid and pepsin in vivo. AB - BRL 24924, a specific 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, was evaluated for effects on gastric secretion of acid and pepsin and possible influences on the effects of serotonin on gastric secretion. Experiments were carried out in conscious dogs with a gastric fistula during a background stimulation of gastric secretion by continuous infusions of pentagastrin, bethanechol or histamine. During infusion of pentagastrin or histamine, BRL 24924, by itself, influenced gastric secretion with stimulation during a low potent background stimulation and inhibition during a potent background stimulation. A serotonin-counteracting effect of BRL 24924 on gastric secretion was found only during infusion of pentagastrin. The secretory stimulation attained by BRL 24924 could be blocked by atropin suggesting a cholinergic mechanism--5-HT4 receptors? The inhibitory effects on gastric secretion and the serotonin-counteracting effects of BRL 24924 are supposed to be via 5-HT3 receptors. PMID- 1916033 TI - Basal and postprandial cholecystokinin values in chronic pancreatitis with and without abdominal pain. AB - We have investigated the relationship between cholecystokinin levels and abdominal pain in patients with chronic pancreatitis. The baseline and postprandial cholecystokinin levels were measured in 15 patients with chronic pancreatitis (8 with and 7 without abdominal pain) and in a reference group of 8 healthy subjects. The baseline, 30 and 60 min postprandial plasma cholecystokinin levels were significantly (p less than 0.05) higher in the patients with pain as compared with the other two groups. No correlation was observed between increased cholecystokinin levels and impairment of the exocrine pancreatic function as assessed by the NBT-PABA test. The increased cholecystokinin levels might be an important factor in the genesis of pain in chronic pancreatitis. PMID- 1916034 TI - Single morning and nightly doses of ranitidine 300 mg: an appraisal of their antisecretory effects by continuous pH monitoring. AB - Gastric acidity of 12 patients with healed duodenal ulcers was continuously monitored over 24 h in order to assess the antisecretory effects of two different administration times of a single daily dose of ranitidine 300 mg. Each patient orally received either (a) placebo at 08.00 h and 22.00 h; (b) ranitidine 300 mg at 08.00 h and placebo at 22.00 h, or (c) placebo at 08.00 h and ranitidine 300 mg at 22.00 h in randomized and double-blind fashion. Each medication was administered on three separate occasions, with intervals of at least 1 week. Both the morning and the bedtime doses of ranitidine were significantly superior (p less than 0.001) to placebo in controlling 24-hour gastric acidity, while, in the same period, ranitidine nocte was more effective (p less than 0.001) than ranitidine mane. During the night, bedtime ranitidine caused more acid inhibition (p less than 0.001) than morning ranitidine, but the opposite (p less than 0.01) occurred during the daytime. This study shows that the antisecretory effect of morning ranitidine during the daytime is less consistent than that achieved by bedtime ranitidine during the nocturnal period. As similar rates of duodenal ulcer healing have recently been achieved with morning and conventional nighttime administration of H2 antagonists, it becomes clear that antisecretory drugs can also be beneficial with an acid inhibition which is shorter-lasting than that which was previously thought to be necessary or, alternatively, that also daytime acidity is important in ulcerogenesis. PMID- 1916035 TI - Hepatitis delta virus RNA detection in chronic HBsAg carriers with and without HIV infection. AB - Hepatitis delta virus (HDV) RNA detection was carried out, using a full-length HDV RNA probe, in serum of 43 patients with chronic HDV infection. Among them, 30 cases (70%) were HDV RNA-positive. With respect to other HDV markers, serum HDAg (detected by immunoblot) was found in 33 patients (77%) and IgM anti-HD in 29 (67%). A similar percentage of HDV RNA-positive patients with and without circulating hepatitis B virus (HBV) DNA (32.5 vs. 37%, respectively) was found. Antibodies against the human immunodeficiency virus (HIV) were detected in 15/43 subjects studied. The presence of HDV RNA was significantly higher (p less than 0.05) in anti-HIV-seropositive cases (93%) than in the HIV-seronegative ones (57%). Moreover, simultaneous HDV and HBV replication was found more frequently (60 vs. 18%, p less than 0.05) and at higher levels among the anti-HIV-positive patients than in the rest. In addition, in most of the anti-HIV-positive subjects, HDV RNA and HBV DNA were constantly positive during a whole year of follow-up. PMID- 1916036 TI - Effect of epidermal growth factor on disaccharidase activity in intestinal epithelial cells of mice. AB - The effects of epidermal growth factor (EGF) on disaccharidase activity in intestinal epithelial cells were studied in mice. In salivectomised mice, the sucrase and maltase activities decreased significantly compared to the control group. When EGF was given to salivectomised mice, the sucrase and maltase activities rose, but still remained below the normal values. These results show that the submaxillary glands produced another factor, beside EGF, which induced glycoprotein enzyme formation in the Golgi complex. PMID- 1916037 TI - Ischemic bowel necrosis induced by endothelin-1: an experimental model in rats. AB - Local intra-arterial administration of endothelin-1 induced small intestinal mucosal damage in rats in a dose-dependent manner. A remarkable decrease in mucosal blood flow (15% of control values) was observed by a laser Doppler flowmetry 10 min after injection of endothelin-1 (1 nmol/kg). Endothelin-1 at this dose induced significant hemorrhagic and necrotic lesions in the small intestinal mucosa 30 min after the injection. Decreased mucosal blood flow was attenuated to some extent by the pretreatment with platelet-activating factor (PAF) inhibitor, CV-6209, superoxide dismutase plus catalase or the calcium antagonist, nicorandil. All these inhibitors significantly prevented the endothelin-1-induced ischemic necrotic damage in the small intestine. These results suggest a potential role of endothelin-1 in the pathogenesis of ischemic bowel diseases in clinical situations and also the possibility that PAF and oxygen-derived free radicals may be involved as secondary mediators in endothelin induced intestinal tissue damage. PMID- 1916038 TI - Liver cirrhosis and chronic calcifying pancreatitis are associated with different morphotypes. AB - The different morphotypes of patients have been determined by sonography of the upper abdomen and statistical calculation according to a previously published method. Patients have been classified into the following 3 groups: 'longilignes', 'normotypes' and 'brevilignes' which fit with ancient anatomical descriptions. In 74 normal controls, there were 21.6% brevilignes and 44.5% longilignes, in alcoholic cirrhosis (n = 31) 77.4 and 6.4%, respectively, in postnecrotic viral cirrhosis (n = 28). 25.0 and 17.8% and in alcoholic chronic calcifying pancreatitis (n = 25) 12.0 and 76.0%. These differences which are significant between all groups show that the morphotype of the human body is different in cirrhotic and pancreatitis patients. As morphotypes preexist to cirrhosis and chronic pancreatitis, this is an argument for the assumed predisposition (possibly hereditary) to cirrhosis and chronic pancreatitis. PMID- 1916039 TI - Effect of omeprazole on nocturnal intragastric pH in cirrhotics with inadequate antisecretory response to ranitidine. AB - Failure of acid suppression by H2-receptor antagonists has been observed, and recently we have found a higher frequency of patients with inadequate antisecretory response among patients with cirrhosis of the liver. In the present study comprising 16 cirrhotics with inadequate antisecretory response to 300 mg of ranitidine, we tested the effect of 40 mg omeprazole. Nighttime intragastric pH was continuously monitored, and a rise in the intragastric pH above 4.0 for more than 6 h following the oral dose at 18.00 h was considered as response. The median pH profile during the omeprazole treatment was significantly higher than with ranitidine (p less than or equal to 0.001). In contrast to 300 mg ranitidine, which despite sufficient plasma levels 2 and 4 h after intake (762 +/ 431 and 802 +/- 668 ng/ml) resulted in a rise in the nighttime intragastric pH above 4 only for 1.8 +/- 1.7 h, after omeprazole for at least 5 days, the intragastric pH was for 10.1 +/- 2.4 of 12 h above 4 during the night (p less than 0.001). The omeprazole plasma levels were 611 +/- 323 and 881 +/- 533 ng/ml after 2 and 4 h. The data obtained with intragastric pH monitoring indicate that the H+K(+)-ATPase inhibitor omeprazole is able to overcome the H2-blocker resistance in cirrhotics. PMID- 1916040 TI - Maturation of the contralaterally recorded auditory brain stem response. AB - Ipsilaterally and contralaterally recorded auditory brain stem responses to 80 dB nHL clicks were recorded from 37 infants, aged 2 weeks to 20 mo and from six adults, all with normal auditory function. With increasing age, contralateral waves A, B, C, and D and ipsilateral waves III and V decreased in latency, with the contralateral morphology more closely resembling the ipsilateral morphology as age increased, especially after the age of 9 mo. The mean latencies and their change with age for waves A and B resembled those of ipsilateral waves III and III', respectively; both waves C and D demonstrated similarities with wave V. Large waveform changes were seen with maturation in the latency region of contralateral waves C and D. In 42 of 43 subjects, wave V latency occurred after wave C and before wave D. Peak to peak amplitudes of contralateral waves A-B and D-E' increased with age, but were smaller than those of ipsilateral I'-III and V V', respectively. The smaller contralateral responses make their use for threshold estimation problematic, especially before the age of 9 months. The contralateral response, however, may help to select wave V in ambiguous cases, and to determine response laterality. PMID- 1916041 TI - On the origin of wave II of the auditory brain stem evoked response. AB - The generators of the several components of the auditory brain stem evoked response (ABR) have yet to be completely identified. However, there is compelling evidence to suggest specific generators for waves I and II, namely the distal and proximal portions of the auditory nerve, respectively. Although there is no question concerning the origin of wave I, there remains some uncertainty as to whether or not wave II arises entirely from the auditory nerve. The purpose of this study was to examine the behavior of wave II, as recorded via vertical versus horizontal derivations, in an effort to determine if wave II in both derivations is equally affected by stimulus manipulations (i.e., as would be presumed from a single generator theory). ABR recordings were obtained from normal-hearing young adults using vertical (hairline-to-ipsilateral mastoid and hairline-to-contralateral mastoid) and horizontal (mastoid-to-mastoid) derivations of responses to clicks presented at a variety of stimulus levels (40 80 dB nHL) and rates (19.9-59.9/sec.). The results indicate a shorter latency for wave II recorded in the horizontal derivation (wave IIa), compared to the vertical derivation (wave IIb). Also, wave IIa was found to be more susceptible to increased stimulus rate and exhibited a different latency behavior than wave IIb. These findings seem difficult to reconcile on the basis of a single generator for waves IIa and IIb. PMID- 1916042 TI - Real ear measures of auditory brain stem response click spectra in infants and adults. AB - This study investigated spectral differences for auditory brain stem response (ABR) clicks measured in infant and adult ear canals. Click stimuli were presented via insert earphones into the ear canals of 15 adults and 11 infants at 30 and 60 dB nHL. An ER-7C probe microphone fed the stimulus to a spectrum analyzer for analysis of spectral content. Infants had spectral peaks at higher frequencies (mean = 2339.77 Hz) than adults (mean = 1618.75 Hz). The infants also exhibited greater variability in their spectral peaks (SD = 669.37) than did adults (SD = 319.0). The total energy of the clicks was the same in infants' and adults' ears. These results indicate that click stimuli such as those used for ABR testing resonate in infant and adult ears differently, and that the resonance in infants is much more variable than the resonance of adults. These findings provide additional evidence for the need to use infant norms when screening infant hearing using the ABR. Similarly, the findings suggest that infant ABRs may be more correlated with higher frequency behavioral thresholds than those assumed for adults. PMID- 1916043 TI - Thresholds of discomfort in young children. AB - Procedures for obtaining thresholds of discomfort from young children are almost nonexistent. This is likely due to the problems encountered in finding a task that they can easily perform. The purpose of this project was to design and test a procedure appropriate to the cognitive and language abilities of 4- to 5-yr-old hearing-impaired children. Data obtained from normally hearing subjects indicate that the procedure can be used with children whose mental ages are at or above 5 yr. PMID- 1916044 TI - Optimization of automated hearing test algorithms: simulations using an infant response model. AB - Computer simulation was used to evaluate several parameters of an automated hearing test algorithm in an attempt to optimize the algorithm for accuracy and efficiency. An infant response model was developed to guide the simulations. Test parameters of interest were starting intensity and stopping rule and their interaction with a measure that is thought to emulate infant reliability, probability of task orientation. Results indicated that stopping rule, within the ranges investigated, had little effect on accuracy but had major impact on efficiency. Starting intensity interacted with the hearing status of pseudosubjects in influencing accuracy. Accuracy was most influenced by probability of task orientation. The simulated test data are compared to data from infants and young children in the accompanying article so that the response model can be evaluated. PMID- 1916045 TI - Optimization of automated hearing test algorithms: a comparison of data from simulations and young children. AB - A five-up, five-down automated staircase procedure was used to explore the effects of variable starting and stopping rules as they interact with infant behavior in influencing the accuracy and efficiency of infant auditory threshold testing. Results from 146 infants were compared to results from computer simulations (see accompanying article) in order to evaluate an infant response model used in the simulations. Results indicate that the automated procedure successfully discriminated between infants with normal versus abnormal tympanograms. In addition, the model accurately predicted infant results in terms of the effects of starting and stopping rules. The model was less useful in predicting the relationship between minimum response levels and false positive rates. PMID- 1916046 TI - Evaluation of three strategies for fitting hearing aids binaurally. AB - Three strategies for evaluating optimum frequency shaping and noise reduction in binaural digital hearing aids were compared in a repeated-measures design, using a new preference-based prescriptive fitting method. These strategies consisted of using preferred frequency shaping and noise reduction values binaurally: (1) based on monaural testing; (2) based on separate evaluations of each ear; and (3) based on evaluation of a second ear while subjects wore an aid programmed with the preferred values in the first ear. Individually preferred characteristics were programmed for 17 hearing-impaired subjects, most of whom exhibited symmetrical sensorineural hearing loss. Each subject was administered intelligibility estimation and midplane localization measurements in the laboratory, as well as a questionnaire survey based on situational listening in the real world. No statistically significant differences in preferences for either frequency shaping or noise reduction were found for the three fitting strategies, suggesting that monaural testing is sufficient in symmetrical cases to provide information for binaural fitting. Related to this finding, differences across binaural conditions were minimal for both intelligibility estimation and localization results. A significant improvement in localization performance under binaural conditions over monaural listening, however, was documented by both the laboratory and the real world data. A strong overall preference for binaural over monaural amplification was also documented under real world conditions. PMID- 1916047 TI - Reliability and intersubject variability of the real ear unaided response. AB - Intratester test-retest reliability of the real ear unaided response (REUR) was determined on 49 ears using the Frye 6500 real ear analyzer. Results revealed mean differences of less than 1 dB for repeat measurements at seven test frequencies between 250 and 4000 Hz. The average peak resonant frequency of the repeated measure was within 16 Hz of the initial measure. In addition, the intersubject variability of the amplitude of REUR was quite large. A range of 7 dB was found at 250 to 500 Hz with the range expanding to 15 to 20 dB at 2000 to 4000 Hz. Also, the peak resonant frequency varied between 2100-4800 Hz. These results are discussed in terms of those dispensers who use the REUR to "custom" order hearing aids. PMID- 1916048 TI - Hearing aid coupler output level variability and coupler correction levels for insert earphones. AB - HA coupler type SPLs were independently determined by two experimenters for five repeated measurements with and without replacement of two ER-3A and two EARTONE 3A insert earphones. Measurements were made using a B&K DB-0138 coupler configured as an HA-1, HA-2 earphone coupler and HA-2 earphone coupler with entrance through a rigid tube referred to as the DB-0138 coupler. The HA-1, HA-2, and DB-0138 SPLs were found to be very stable (+/- 0.2 dB) for all intra- and interexperimenter measurements for each insert earphone and coupler type from 125 to 8000 Hz. Averaged across both experimenters and all repeated measurements, the mean HA-1 and HA-2 coupler SPLs were similar for each insert earphone from 125 to 8000 Hz. The mean HA-1, HA-2, and DB-0138 coupler SPLs were similar for each insert earphone from 125 to 2000 Hz; however, from 3000 to 8000 Hz the DB-0138 coupler SPLs were higher than the HA-1 and HA-2 coupler SPLs for each insert earphone. This occurred because of the geometrical differences between the insert earphone to coupler connections and coupler types. The HA-1 minus DB-0138 and HA 2 minus DB-0138 coupler SPL differences, or coupler correction levels, could be explained by quarter-wave resonances and stepped-diameter tubing systems creating acoustic horn effects. PMID- 1916049 TI - Increased plasma plasminogen activator inhibitor 1 levels. A possible link between insulin resistance and atherothrombosis. AB - According to recent prospective studies, hypofibrinolysis due to elevated plasma plasminogen activator inhibitor 1 levels appears to be an independent risk factor for myocardial reinfarction in men, and hyperinsulinaemia, a major indicator of insulin resistance is considered as a risk factor for coronary disease. It has recently been shown that insulin resistance is accompanied by an increased plasma plasminogen activator inhibitor 1 concentration: A significant correlation coefficient was demonstrated between plasminogen activator inhibitor 1 and fasting plasma insulin in the normal population, in obese subjects, in Type 2 (non-insulin-dependent) diabetic patients and in angina pectoris. Attempts to decrease insulin resistance such as fasting, diet, or administration of an oral anti-diabetic drug such as Metformin induced a parallel decrease in plasma insulin and plasminogen activator inhibitor 1 levels. This inhibitor is produced by endothelial cells and by hepatocytes in culture. Plasminogen activator inhibitor 1 synthesis by hepatocytes in culture was stimulated by an increasing insulin concentration, or low density lipoproteins, whereas the endothelial cell synthesis was stimulated by very low density lipoproteins especially when they were obtained from hypertriglyceridaemic patients. Therefore, a direct effect of insulin or lipoprotein changes on the cells which synthesize plasminogen activator inhibitor 1 could be responsible for its increased plasma concentration in insulin resistance states. The increase in plasma plasminogen activator inhibitor 1 levels linked to hyperinsulinaemia is a tempting partial explanation for the association between insulin resistance and coronary disease. PMID- 1916050 TI - Influence of affinity of antibodies upon their detection by liquid phase radiobinding assay and solid phase enzyme linked immunosorbent assay. Demonstration using monoclonal antibodies raised against rDNA human proinsulin. AB - Hybridomas producing proinsulin antibodies were cloned by limiting dilution of cell cultures obtained by fusion of splenocytes of immunized mice with immortal myeloma cells. Some proinsulin monoclonal antibodies crossreacted with labelled insulin but none did with labelled C-peptide indicating that the involved epitopes were at one of the insulin/C-peptide junctions or included in the insulin moiety. Hybridoma supernatants were assayed for IgG concentration by a solid phase assay and for ligand binding by a radiobinding assay and an enzyme linked immunosorbent assay. The half-life of immune complexes formed with radioligand was measured and, as expected, correlated with affinity as measured by the method of Scatchard. Antibody titres determined by enzyme linked immunosorbent assay did not correlate to those measured by radiobinding assay. IgG concentration correlated to enzyme linked immunosorbent assay titres but not to radiobinding assay titres. Finally, a significant correlation was found between radiobinding assay titre and the product of enzyme linked immunosorbent assay titre by the period of immune complexes. It is concluded that, except for very low affinity antibodies, enzyme linked immunosorbent assay is a capacity assay whereas radiobinding assay is influenced by both antibody concentration and affinity. The former assay is thus best suited to detecting low affinity antibodies whereas the latter is more efficient in the presence of low levels of high affinity antibodies. PMID- 1916051 TI - Changes in vitreal oxygen tension distribution in the streptozotocin diabetic rat. AB - Measurements of vitreal oxygen tension have been made for the first time in the streptozotocin-induced diabetic rat eye. A total of 36 Sprague Dawley rats were divided into a control (n = 18) and streptozotocin injected group (n = 18), and after 5-6 weeks of established hyperglycaemia, an acute experiment was performed in which vitreal oxygen tension profiles were determined with oxygen sensitive microelectrodes. The control rats had significant oxygen tension gradients in the vitreous close to retinal arteries with relatively flat oxygen tension profiles close to retinal veins and intermediate regions. All control rats had a substantial arteriovenous oxygen tension difference when measurements were made on retinal arteries and veins. In contrast the oxygen tension profiles measured in the vitreous of streptozotocin rats showed markedly reduced oxygen gradients in the vicinity of retinal arteries and a smaller arteriovenous oxygen tension difference. In both groups of rats, for distances of 500 microns and greater from the retina (mid vitreous) a plateau oxygen tension value was observed. No significant difference was found in this mean mid vitreous value between the control rats and diabetic rats under the same systemic conditions. We conclude that there are significant changes in oxygen tension near retinal arteries in streptozotocin-induced diabetes before any histopathological changes are evident. PMID- 1916052 TI - Altered expression of glucose transporter isoforms with aging in rats--selective decrease in GluT4 in the fat tissue and skeletal muscle. AB - To elucidate the cellular mechanisms of glucose intolerance associated with aging, both the protein and mRNA levels of glucose transporter isoforms were studied in the various tissues of young (7-week-old) and aged (20-month-old) rats. GluT4 (adipose/muscle-type glucose transporter) protein, which is specifically expressed in insulin-responsive tissues, was selectively decreased per milligram of cellular membrane protein in both the epididymal fat tissues and the gastrocnemius muscle of the aged rats compared with the young rats. When the changes in total cellular membranes per gram of tissue are taken into account, a further decrease in GluT4 protein per gram of tissue was observed in the tissues of the aged rats compared with the young rats. The decreased amount of GluT4 protein in the fat tissues of the aged rats is probably due to the decreased protein synthesis rather than the stability, since GluT4 mRNA/micrograms of cellular total RNA was also decreased. In contrast, GluT4 mRNA in the gastrocnemius muscle was rather increased and a ratio of GluT4 protein/GluT4 mRNA was decreased by 70% in the aged rats, suggesting that the translational efficiency and/or stability of GluT4 protein is decreased in the skeletal muscle of the aged rats compared with the young rats. GluT2 (liver-type glucose transporter) protein and mRNA in the liver were also decreased in the aged rats, while no apparent decrease in GluT1 (HepG2/brain-type glucose transporter) protein/mg of cellular membrane protein was observed in the skeletal muscle and fat tissues of the aged rats compared with the young rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916053 TI - Different aetiologies of type 2 (non-insulin-dependent) diabetes mellitus in obese and non-obese subjects. AB - Insulin responses to intravenous glucose infusion and glucose utilization during hyperinsulinaemic euglycaemic clamp were determined in a large homogeneous group of 65-year-old male subjects. Twenty-eight had untreated Type 2 (non-insulin dependent) diabetes mellitus and the remaining 44 control subjects had a normal glucose tolerance. Diabetic patients with abdominal obesity displayed peripheral insulin resistance in combination with defective insulin secretion, whereas non obese diabetic patients showed only a secretory defect. Thus, Type 2 diabetes in obese and non-obese elderly male subjects may take two forms where the cause of hyperglycaemia differs. PMID- 1916054 TI - Simple empirical assessment of beta-cell function by a constant infusion of glucose test in normal and type 2 (non-insulin-dependent) diabetic subjects. AB - The plasma insulin or C-peptide response to a 90-min constant glucose infusion 5 mg.kg ideal body weight-1.min-1 provides Beta-cell assessment comparable to more intensive methods. In 14 diet-treated Type 2 (non-insulin-dependent) diabetic subjects and 12 non-diabetic subjects, plasma insulin and C-peptide concentrations gave near linear plots against simultaneous glucose values. The 'glucose-insulin and glucose-C-peptide vectors' (G-I and G-C vectors), could be extrapolated to predict insulin and C-peptide levels during a 12 mmol/l hyperglycaemic clamp. Predicted concentrations correlated with clamp concentrations, r = 0.94 and r = 0.98 respectively, p less than 0.001, validating the vectors as empirical glucose dose-response curves. The vector slopes correlated highly with %Beta, a mathematical model-derived measure of Beta-cell function using constant infusion of glucose model assessment, Spearman r = 0.95 and 0.93 for insulin and C-peptide, respectively. G-I vector slopes in 21 diet treated Type 2 diabetic subjects with fasting glucose (mean + 1 SD) 7.5 +/- 2.3 mmol/l, were lower than in 28 non-diabetic subjects, (geometric mean, 1 SD range, 8.4 pmol/mmol (3.3-21.0) and 25.1 pmol/mmol (14.3-44.1), p less than 0.001, respectively), indicating an impaired Beta-cell response. The G-I vector slopes correlated with obesity in both groups (r = 0.54 p less than 0.02 and 0.72, p less than 0.001 respectively), and, in 15 non-diabetic subjects, correlated inversely with insulin sensitivity as measured by a euglycaemic clamp (r = -0.66, p less than 0.01). Thus, Beta-cell function needs to be interpreted in relation to obesity/insulin resistance and, taking obesity into account, only 4 of 21 diabetic patients had Beta-cell function (G-I vector slope) in the non-diabetic range. The fasting plasma glucose in the diabetic subjects correlated inversely with the obesity-corrected G-I and G-C vector slopes (partial r = -0.57, p less than 0.01 and -0.86, p less than 0.001, respectively). The insulin or C-peptide response to the glucose infusion provides a direct empirical measure of the Beta cell function, which can be interpreted in relation to obesity or to insulin resistance to assess underlying pancreatic responsiveness. PMID- 1916055 TI - Characterization of the insulin-antagonistic effect of growth hormone in man. AB - The insulin-antagonistic effect of growth hormone was characterized by infusing the hormone at three different infusion rates (6, 12 or 24 mU.kg-1.min-1) for one h in 11 healthy subjects. The insulin effect was measured with the euglycaemic clamp technique combined with D-(3-3H)-glucose infusion to evaluate glucose production and utilization. A control study with NaCl (154 mmol.l-1) infusion was also performed. The insulin levels during the clamps were similar in all studies (36 +/- 0.2 mU.l-1). Peak growth hormone levels were reached at 60 min (growth hormone 6 mU.kg-1.h-1: 31 +/- 5; growth hormone 12 mU.kg-1.h-1: 52 +/- 4 and growth hormone 24 mU.kg-1.h-1; 102 +/- 8 mU.l-1). The insulin-antagonistic effect of growth hormone started after approximately 2 h, was maximal after 4-5 h (approximately 39% inhibition of glucose infusion rate between control and growth hormone 24 mU.kg-1.h-1) and lasted for 6-7 h after peak levels. The resistance was due to a less pronounced insulin effect both to inhibit glucose production and to stimulate glucose utilization. Growth hormone infusion of 12 mU.kg-1.h-1 induced a similar insulin-antagonistic effect as the higher infusion rate whereas 6 mU.kg-1.h-1 induced a smaller response with a duration of 1 h between 3-4 h after peak levels of growth hormone. The present study demonstrates that growth hormone levels similar to those frequently seen in Type 1 (insulin-dependent) diabetic patients during poor metabolic control or hypoglycaemia, have pronounced insulin-antagonistic effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916057 TI - Mortality in Israeli Jewish patients with type 1 (insulin-dependent) diabetes mellitus diagnosed prior to 18 years of age: a population based study. AB - A total of 614 Jewish patients under the age of 18 with Type 1 (insulin dependent) diabetes mellitus, diagnosed in Israel during the period 1 January 1965 to 31 December 1979, were identified by exhaustive screening of all possible sources. Mortality experience of this cohort was updated to 31 March 1988 through the Central Population Registry and 14 deaths were identified. The ascertainment rate for diagnosed cases as well as for deaths is estimated at about 95%. There was a significantly higher (p less than 0.001) by 3.2-fold excess mortality relative to the age and sex-adjusted mortality as expected the general Jewish population in Israel. This excess was due to three cause-of-death categories: diabetic ketoacidosis (n = 3; p less than 0.001), cardiovascular diseases (n = 3; p less than 0.001) and infections (n = 2; p = 0.03). The rate of malignancies (n = 2), external causes (n = 3) and other general causes (n = 1) did not differ significantly from that expected. During the first 15 years of the disease cumulative mortality resembled that of the general population, with a subsequent steep increase so that by 20 years disease duration, the rate was four-fold higher than expected. This mortality pattern was similar irrespective of age at onset, sex and ethnic group (Ashkenazi vs non-Ashkenazi Jews). A factor contributing to the lack of increase in mortality rate in the first 15 years of Type 1 diabetes may be the comprehensive multidisciplinary treatment approach employed for most juvenile diabetic patients in Israel leading to early referral and an overall better metabolic control. PMID- 1916056 TI - Gestational diabetes mellitus: evidence for autoimmunity against the pancreatic beta cells. AB - Diabetes mellitus is a frequent transient or rare permanent complication of pregnancy. The role of autoimmune phenomena in this gestational form of diabetes is incompletely understood. We have examined sera from 312 pregnant women who had abnormal glucose tolerance (based on a screening examination during the second trimester) for the presence of islet cell surface antibodies or insulin autoantibodies. Fifty-eight of these women were lost to follow-up. Of the remaining subjects, 144 (57.1%) had gestational diabetes diagnosed by formal glucose tolerance testing and the others (42.9%) were normal. Sixty percent of the women with gestational diabetes eventually required insulin to control their blood glucose during pregnancy. One serum from the non-diabetic women was positive for insulin antibodies (0.9%); 8 of the sera from the patients with gestational diabetes were positive (5.6%). Subsequent analysis revealed that all nine of the women whose sera were positive for insulin autoantibodies had been treated with insulin previously. Islet cell surface antibodies were strongly correlated with gestational diabetes. Forty-five of 144 gestational diabetic sera were positive (31.3%) whereas only 9 of 108 suspect control sera (8.3%) and 7 of 60 unknown sera (11.7%) were positive. These data suggest that a high percentage of pregnant women who screen positive for glucose intolerance have serological evidence of an autoimmune response against the pancreatic islets, in spite of the state of relative immune tolerance during pregnancy. These data suggest that autoimmune phenomena may play a role in gestational diabetes and that the presence of islet cell antibodies can predict insulin-requiring gestational diabetes. PMID- 1916059 TI - Reproducibility of insulin sensitivity measured by the minimal model method. AB - Insulin resistance is a critical component underlying the altered glucose homeostasis in a variety of metabolic and non-metabolic disorders. Aging, body fat distribution, obesity, diabetes mellitus or hypertension are well recognized conditions associated with an impaired tissue sensitivity to insulin action. Apart from such constant factors, insulin sensitivity can be acutely modified by independent variables such as physical exercise, dietary factors, alcohol intake or harmless drugs. To evaluate the day-to-day intra-individual variation in insulin sensitivity, glucose homeostasis and lipid profiles, we investigated the insulin sensitivity index (S1) (determined by the minimal model method of Bergman), basal and post-glucose-load insulin and glucose levels, serum total triglyceride and lipoprotein cholesterol fractions in 15 healthy young men (24 +/ 1 year, mean +/- SEM), on two different occasions at an interval of 3 weeks (days 1 and 21), after 3 days of a standard dietary regimen and after an overnight fast. Blood pressure, heart rate, body weight and 24 h urinary sodium excretion were almost identical in the two phases. S1(day 1) varied from 4.2 to 15.8 x 10(-4).min-1 pro microU/ml (mean: 10.2 +/- 0.9) and correlated with S1(day 21) (11.2 +/- 1.2 x 10(-4).min-1 pro microU/ml, r = 0.78, p less than 0.0007). The slope of the relationship did not differ from 1 (1.01, p greater than 0.90), the intercept was close to the origin (0.8, p greater than 0.73) and the coefficient of variation was 14.4%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916058 TI - Decreased hepatic glucagon responses in type 1 (insulin-dependent) diabetes mellitus. AB - The effect of glucagon infusion on hepatic glucose production during euglycaemia was evaluated in seven Type 1 (insulin-dependent) diabetic patients and in ten control subjects. In the diabetic subjects normoglycaemia was maintained during the night preceding the study by a variable intravenous insulin and glucose infusion. During the study endogenous insulin secretion was suppressed by somatostatin (450 micrograms/h) and replaced by insulin infusion (0.15 mU.kg 1.min-1). 3H-glucose was infused for isotopic determination of glucose turnover. Plasma glucose was clamped at 5 mmol/l for 2 h 30 min and glucagon (1.5 ng.kg 1.min-1) was then infused for the following 3 h. Hepatic glucose production and glucose utilisation were measured during the first, second and third hour of the glucagon infusion. Basal hepatic glucose production (just prior to glucagon infusion) was similar in diabetic (1.2 +/- 0.3 mg.kg-1.min-1) and control (1.6 +/ 0.1 mg.kg-1.min-1) subjects. In diabetic patients hepatic glucose production rose slowly to 2.1 +/- 0.5 mg.kg-1.min-1 during the first hours of glucagon infusion and stabilized at this level (2.4 +/- 0.5 mg.kg-1.min-1) in the third hour. In control subjects hepatic glucose production increased sharply to higher levels than in the diabetic subjects (3.4 +/- 0.3 mg.kg-1.min-1) during the first and second hour of glucagon infusion (p less than 0.05) and then gradually fell (2.9 +/- 0.4 mg.kg-1.min-1) during the third hour. In conclusion, when stimulated with glucagon at a physiologic plasma concentration diabetic patients had 1) an overall reduced hepatic glucose production response and 2) an abnormal sluggish response pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916060 TI - Height and glucose tolerance in adult subjects. AB - In a prospective study concerning the pathogenesis of impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus, 346 subjects with no clinical history of diabetes were given a standard 75 g oral glucose tolerance test. The expected positive associations between 120-min plasma glucose concentration and age and body mass index were observed in both sexes and between 120-min plasma glucose and waist/hip ratio in male subjects. An unexpected negative correlation was found between 120-min plasma glucose and height in both sexes (r = -0.23, (95% confidence interval, -0.38 - -0.07) p less than 0.007 for male subjects and r = -0.24, (-0.37 - -0.11) p less than 0.006 for female subjects). These negative associations with height remained significant after controlling for age and body mass index in male subjects but not in female subjects. In the latter a highly significant negative relationship of height with age was recorded (r = -0.33, (-0.45 - -0.20) p less than 0.0001). Comparison between individuals with impaired glucose tolerance and control subjects matched for sex, age and body mass index showed that subjects with impaired glucose tolerance are significantly shorter. Mean (+/- SEM) height in the male subjects with impaired glucose tolerance (n = 29) was 173.4 +/- 1.1 cm vs 176.9 +/- 1.3 cm in control subjects, p = 0.02. In the female subjects (n = 39) mean (+/- SEM) height was 159.4 +/- 1.0 cm vs 162.4 +/- 1.0 cm in control subjects, p = 0.02. The negative relationship between height and glucose tolerance is a new epidemiological observation which has not been previously reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916061 TI - The Fourth International Serum Exchange Workshop to standardize cytoplasmic islet cell antibodies. The Immunology and Diabetes Workshops and Participating Laboratories. PMID- 1916062 TI - Epidemiological and ethical consiluations on trials with immunotherapy in pre type 1 (insulin-dependent) diabetes mellitus. PMID- 1916063 TI - Cell sorting within the prestalk zone of Dictyostelium discoideum. AB - The prestalk zone of slugs of Dictyostelium discoideum has been shown to contain three subregions in which the extracellular matrix genes ecmA and ecmB are differentially expressed; it is generally thought that these regions are defined by extracellular signals. Using beta-galactosidase as a cell marker, we have shown that cells can sort specifically to all three regions. Cells from the posterior-prestalk zone ("prestalk 0 zone") which are injected into the slug tip move within 60 min back to their position of origin. When cells from the anterior prestalk zone (presumably containing a mixture of ecmA and ecmB expressers) are transplanted to the posterior prestalk zone, they move to the tip ("prestalk A zone") within 1 h and about 30 min subsequently are often found in a cone-shaped region within the tip ("prestalk B zone"). Cells transplanted to their own positions do not move significantly within this period. Since the subregions of the prestalk zone can be defined by sorting, it is possible that they are normally formed in this way rather than by position-dependent signals. Cells transplanted without a change in anterior-posterior position and cells which have sorted back to their positions of origin eventually spread out throughout the prestalk zone. This suggests that sorting preferences of cells are respecified. When posterior prestalk cells are transplanted to the prespore zone, respecification of sorting preference is suspended until the cells return to the prestalk zone and anterior-prestalk cells acquire posterior-prestalk sorting preferences. PMID- 1916064 TI - Purification and characterization of developmentally regulated AMP deaminase from Dictyostelium discoideum. AB - AMP deaminase, the enzyme that catalyzes the conversion of adenosine monophosphate (AMP) to inosine monophosphate (IMP) and ammonia, was purified from the cellular slime mold, Dictyostelium discoideum in the nutrient-deprived state. The native enzyme had an apparent molecular weight of 199,000 daltons. Its apparent Km was 1.6 mM and its Vmax was 1.0 mumol min-1 mg-1, as measured by the release of IMP From AMP. The enzyme, like other AMP deaminases, was found to be activated by ATP, and inhibited either by GTP or inorganic phosphate. It was also specific for the deamination of AMP. Deaminase activity was increased either when vegetative cells were placed in a nutrient-deprived medium (for up to 6 h) or when vegetative cells were treated with the drug hadacidin. In cells actively growing in complete media, enzyme activity was more non-specific, hydrolyzing adenosine as well as AMP. AMP deaminase in D. discoideum appears to be stage specific and developmentally regulated, possibly serving to regulate the adenylated nucleotide pool and the interconversion to guanylated nucleotides during early morphodifferentiation. PMID- 1916065 TI - Tunicamycin-inducible polypeptide synthesis during Xenopus laevis embryogenesis. AB - Tunicamycin treatment of Xenopus laevis embryos enhanced the synthesis of a specific set of polypeptides with molecular masses of 98, 78, 59 and 58 kDa. The 78-kDa polypeptide was tentatively identified as glucose-regulated protein (GRP) 78 on the basis of molecular mass, pl (5.2), and tunicamycin inducibility, which took place upon treating embryos after the midblastula transition (MBT). The synthesis of a polypeptide with this electrophoretic mobility was detected but was not tunicamycin-inducible at stages prior to the MBT. GRP78 mRNA was detectable before the MBT but was not inducible by tunicamycin until the tailbud stage. A comparison of tunicamycin-induced polypeptide synthesis in Xenopus embryos, A6 cell line, and white blood cells by 2D-PAGE and fluorography revealed three spots in the GRP78 region of the gel. One was observed in both embryos and adult cells; another was adult-specific; and the third one was possibly an embryo specific form. These results suggest that GRP78 synthesis might undergo a switch from an embryonic to an adult pattern during Xenopus development. PMID- 1916066 TI - Comparison of morphological and biochemical characteristics of cultured chondrocytes isolated from proliferative and hypertrophic zones of bovine growth plate cartilage. AB - Primary cultures of chondrocytes isolated from the proliferative and hypertrophic zones of bovine growth plate cartilage were established, and their morphological and biosynthetic characteristics were compared. High-cell-density monolayer cultures maintained a predominantly chondrocytic morphology, preserved their zone specific collagen phenotype, and produced an abundant proteoglycan matrix. In contrast, monolayer cultures plated at low cell densities contained many cells with fibroblastic morphology and initiated the synthesis of type I collagen within 72 h following seeding. On a per cell basis, the proliferative zone chondrocytes displayed greater biosynthetic activity than chondrocytes from the hypertrophic region. Characterization of newly synthesized collagens showed that type II collagen was the major biosynthetic product of both types of cells. In contrast, type X collagen was synthesized exclusively by hypertrophic chondrocytes and represented about 20% of the total collagen produced by these cells. The type X collagen molecules synthesized by the hypertrophic cells contained disulfide bonds within their triple-helical domains and assembled into a high-Mr aggregate. When polymerase chain reaction (PCR) was employed to amplify type X collagen sequences from cDNA obtained by reverse transcription of mRNA from cultures of both types of chondrocytes, only the hypertrophic chondrocyte mRNA yielded PCR amplification products indicative of the presence of type X collagen transcripts. PMID- 1916067 TI - Tissue and age-specificity of post-translational modifications of N-cadherin during chick embryo development. AB - Our previous studies indicated that regulation of N-cadherin expression differs spatially and temporally among tissues of the eye, possibly reflecting the distinct roles it has in the development and maintenance of eye tissues. To understand this regulation of N-cadherin expression and its function in different tissues during embryonic development, we investigated the post-translational modifications of N-cadherin and its association with the cytoskeleton. We show that N-cadherin is a sulfated and phosphorylated protein. The phosphorylation of N-cadherin occurs in an age- and tissue-specific pattern during development in the neural retina, brain, lens and heart. The extent of sulfation of N-cadherin is also age-dependent, and both sulfated and unsulfated pools of N-cadherin exist in the same tissue as indicated by two-dimensional electrophoresis. The degree of association of N-cadherin with the cytoskeleton differs from one tissue to another, as well as within a single tissue at different stages of development. A positive correlation was found between the extent, developmental timing, and tissue specificity of N-cadherin phosphorylation and the degree of N-cadherin association with the cytoskeleton. Our results suggest the existence of a microheterogeneous population of N-cadherin molecules, within which posttranslational modification of N-cadherin may affect its association with the cytoskeleton and its expression and function during development. PMID- 1916068 TI - Amino acid sequence of bovine muzzle epithelial desmocollin derived from cloned cDNA: a novel subtype of desmosomal cadherins. AB - Desmosomes are cell-type-specific intercellular junctions found in epithelium, myocardium and certain other tissues. They consist of assemblies of molecules involved in the adhesion of specific cell types and in the anchorage of cell-type specific cytoskeletal elements, the intermediate-size filaments, to the plasma membrane. To explore the individual desmosomal components and their functions we have isolated DNA clones encoding the desmosomal glycoprotein, desmocollin, using antibodies and a cDNA expression library from bovine muzzle epithelium. The cDNA deduced amino-acid sequence of desmocollin (presently we cannot decide to which of the two desmocollins, DC I or DC II, this clone relates) defines a polypeptide with a calculated molecular weight of 85,000, with a single candidate sequence of 24 amino acids sufficiently long for a transmembrane arrangement, and an extracellular aminoterminal portion of 561 amino acid residues, compared to a cytoplasmic part of only 176 amino acids. Amino acid sequence comparisons have revealed that desmocollin is highly homologous to members of the cadherin family of cell adhesion molecules, including the previously sequenced desmoglein, another desmosome-specific cadherin. Using riboprobes derived from cDNAs for Northern-blot analyses, we have identified an mRNA of approximately 6 kb in stratified epithelia such as muzzle epithelium and tongue mucosa but not in two epithelial cell culture lines containing desmosomes and desmoplakins. The difference may indicate drastic differences in mRNA concentration or the existence of cell-type-specific desmocollin subforms. The molecular topology of desmocollin(s) is discussed in relation to possible functions of the individual molecular domains. PMID- 1916069 TI - Evaluation of the primary skin irritation and allergic contact sensitization potential of transdermal triprolidine. AB - A transdermal patch for the OTC antihistamine, triprolidine (TP), might provide benefits in terms of increased efficacy and reduced sedative side effects. However, concerns over potential irritant or allergic contact sensitization (ACS) skin reactions necessitated through skin toxicity testing before and during initial clinical development. Initial effort was expended on development of a binary vehicle delivery system comprised of TP in 0.5% oleic acid (OA) in propylene glycol (PG). Rabbit skin irritation and Buehler guinea pig skin sensitization testing indicated that this TP/OA/PG formula had both skin irritation and ACS potential. Both tests underestimated, to some degree, the skin toxicities observed in later clinical testing. In clinical tests, skin irritation was due mainly to the OA/PG vehicle, but was enhanced in the presence of high TP concentrations. Of 26 subjects enrolled in a rising dose clinical pharmacokinetics study, one subject exposed twice to TP/OA/PG presented with delayed skin reactions suggestive of ACS. Positive diagnostic patch test results for this subject and four out of five other twice-exposed study subjects suggested that the TP/OA/PG formula had a very high ACS potential. Subsequent predictive clinical patch testing was conducted with a buffered aqueous TP formula which provided in vitro skin penetration of the drug equivalent to the TP/OA/PG formula. These clinical studies demonstrated that TP itself had no significant irritation potential but still induced ACS reactions in a high proportion of test subjects. The incidence of adverse skin reactions to TP was considered to be too high relative to the degree of improved therapeutic benefit of this delivery form. On this basis, all technology development effort was discontinued. PMID- 1916070 TI - Acute neurotoxicity of sodium azide and nitric oxide. AB - Sodium azide is a chemical of rapidly growing commercial importance with a high acute toxicity and an unknown mechanism of action. Although it has some chemical properties and biological effects in common with cyanide, its lethality does not appear to be due to inhibition of cytochrome oxidase. Unlike cyanide it is a potent vasodilator and inhibitor of platelet aggregation presumably by virtue of its conversion to nitric oxide in vivo and in isolated preparations of blood vessels and thrombocytes. It is not clear whether the high toxicity of azide is due to nitric oxide or to the parent anion. Of a number of possible azide antagonists tested in intact mice only phenobarbital in both anesthetic and subanesthetic doses afforded statistically significant protection against death. Diazepam, phenytoin, and an anesthetic dose of a ketamine/xylazine combination had no effect. Major motor seizures are sometimes seen in human azide poisoning, and these are a regular feature of azide poisoning in laboratory rodents. Solutions of nitric oxide given systemically to mice produced no signs of toxicity, but doses 1,000-fold lower placed in the cerebroventricular system of rats produced brief but violent tonic convulsive episodes. A dose of 0.61 mmol/kg azide as given systemically regularly produced convulsions whereas a dose of 6 mumol/kg given icv produced seizures in rats. The icv convulsive dose of azide was 50-fold larger than the icv dose of nitric oxide. These results suggest that azide lethality is due to enhanced excitatory transmission in the central nervous system perhaps after its conversion to nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916071 TI - Effects of oral administration of a high-molecular-weight crosslinked polyacrylate in rats. AB - Oral feeding studies of a crosslinked, high-molecular-weight polyacrylate polymer (PA) were conducted to (1) characterize the biological effects following exposure to either 0, 300, 1000, or 3000 mg PA/kg/day for 93 days; (2) characterize the fecal and urinary mineral excretion at these same dose levels; and (3) monitor the absorption, distribution, and excretion (ADE) of radiolabeled PA following a single oral exposure. The subchronic study results indicate that dietary intake of up to 3000 mg/kg/day PA had no adverse histopathology, hematology, body weight, or clinical chemistry effects in rats. Dietary exposure to PA did, however, result in an elevation in urinary excretion of sodium and phosphorus, whereas excretion of magnesium, calcium, and potassium was lowered. A more detailed study demonstrated that although the urinary excretion of these minerals was changed, total recovery of the minerals (feces + urine), except for sodium, was not different from that for controls. An increase in sodium excretion was expected since PA was in the form of a sodium salt. The ADE studies following a single oral dose of PA indicate that the majority of dosed PA (91.9%) was excreted in the feces. As expected, a small percentage (approximately 3.5%) was absorbed, possibly metabolized, and excreted. In summary, the oral administration of high levels of PA resulted in (1) no histological, hematological, or clinical chemistry changes; (2) no alteration in the overall mineral excretion (feces + urine) with the exception of sodium; and (3) primarily fecal excretion of orally administered PA. PMID- 1916072 TI - Evaluation of seven in vitro alternatives for ocular safety testing. AB - Seven in vitro assays were evaluated to determine if any were useful as screening procedures in ocular safety assessment. Seventeen test materials (chemicals, household cleaners, hand soaps, dishwashing liquids, shampoos, and liquid laundry detergents) were tested in each assay. In vivo ocular irritation scores for the materials were obtained from existing rabbit low volume eye test (LVET) data. The seven assays evaluated included the silicon microphysiometer (SM), luminescent bacteria toxicity test (LBT), neutral red assay (NR), total protein assay (TP), Tetrahymena thermophila motility assay (TTMA), bovine eye/chorioallantoic membrane assay (BE/CAM), and the EYTEX system (ETS). For the seventeen materials used in this study there was a significant correlation between the in vivo irritant potential and in vitro data for all the tests except the EYTEX System (SM, r = -0.87; LBT, r = -0.91; NR, r = -0.85; TTMA, r = 0.78; TP, r = -0.86; ETS, r = 0.29). The irritation classifications provided by the BE/CAM also did not correspond with the actual in vivo irritancy potential of the test materials. The result of this study suggested it may be possible to classify materials into broad irritancy categories with some of the assays. This would allow their use as screens prior to limited in vivo confirmation in the ocular safety assessment process. PMID- 1916073 TI - Two-week, repeated inhalation exposure of F344/N rats and B6C3F1 mice to ferrocene. AB - Ferrocene (dicyclopentadienyl iron; CAS No. 102-54-5) is a relatively volatile, organometallic compound used as a chemical intermediate, a catalyst, and as an antiknock additive in gasoline. It is of particular interest because of its structural similarities to other metallocenes that have been shown to be carcinogenic. F344/N rats and B6C3F1 mice were exposed to 0, 2.5, 5.0, 10, 20, and 40 mg ferrocene vapor/m3, 6 hr/day for 2 weeks. During these exposures, there were no mortality and no observable clinical signs of ferrocene-related toxicity in any of the animals. At the end of the exposures, male rats exposed to the highest level of ferrocene had decreased body-weight gains relative to the weight gained by filtered air-exposed control rats, while body-weight gains for all groups of both ferrocene- and filtered air-exposed female rats were similar. Male mice exposed to the highest level of ferrocene also had decreased body-weight gains, relative to controls, while female mice had relative decreases in body weight gains at the three highest exposure levels. Male rats had a slight decrease in relative liver weight at the highest level of exposure, whereas no relative differences in organ weights were seen in female rats. Male mice had exposure-relative decreases in liver and spleen weights, and an increase in thymus weights, relative to controls. For female mice, relative decreases in organ weights were seen for brain, liver, and spleen. No exposure-related gross lesions were seen in any of the rats or mice at necropsy. Histopathological examination was done only on the nasal turbinates, lungs, liver, and spleen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916074 TI - The acute effects of S-(1,2-dichlorovinyl)-L-cysteine and related chemicals on renal function and ultrastructure in the pentobarbital-anesthetized dog: structure-activity relationships, biotransformation, and unique site-specific nephrotoxicity. AB - S-(1,2-Dichlorovinyl)-L-cysteine (L-DCVC), a substrate for the renal cysteine conjugate beta-lyase, and other related chemicals were administered intravenously to pentobarbital-anesthetized dogs. Six pertinent findings emerged regarding their nephrotoxicity. (1) L-DCVC was acutely nephrotoxic in the dog. (2) The earliest indicator of L-DCVC-induced renal damage was an increase in the urinary excretion rate of protein. (3) Contrary to results from other species, L-DCVC induced renal ultrastructural lesions only in the S1 and S2 cells of the proximal tubule. (4) The toxicity of L-DCVC (23.15 mumol/kg, iv) to S1 and S2 cells resulted from a direct tubular insult and not from overlapping episodes of hypoxia or ischemia. (5) L-DCVC could be detected in plasma only during the first 30 min after its injection. In addition, no L-DCVC and only small amounts of N acetyl-L-DCVC and S-(1,2-dichlorovinyl)mercaptoacetic acid (DCV-MAA) (1.5% and less than 1% of the administered dose, respectively) were detectable in urine during the 6 hr following L-DCVC administration. (6) DCV-MAA and chloroacetic acid as well as other compounds that are not substrates for the renal cysteine conjugate beta-lyase (i.e., S-allyl-L-cysteine, vinthionine, and S-(1,2 dichlorovinyl)-D,L-alpha-methylcysteine) were not acutely nephrotoxic. These findings provide indirect evidence for the involvement of beta-lyase in the toxification of L-DCVC in the dog. PMID- 1916075 TI - Mechanisms of pulmonary edema induced by an organophosphorus compound in anesthetized dogs. AB - To determine the mechanism governing pulmonary edema induced by an organophosphorus compound, S-(2-diisopropylaminoethyl)-O-ethylmethyl phosphonothiolate (VX), lung lymph flow and lymph-to-plasma protein concentration ratio were measured in six anesthetized, open-chest, mechanically ventilated beagle dogs before and after intravenous injection of 6 micrograms/kg of VX. Systemic and pulmonary hemodynamic data (heart rate, aortic blood flow, and left atrial, systemic arterial, pulmonary arterial, and pulmonary capillary pressures) were continuously recorded. Arterial blood gases and pH were measured every 30 min. Histological examinations and lung water content measurements were also carried out. Following VX injection, lung lymph flow increased (from 109 +/- 38 to 179 +/- 66 microliters/min, p less than 0.05) while lymph-to-plasma protein concentration ratio remained unchanged (from 0.64 +/- 0.14 to 0.62 +/- 0.12, N.S.). Neither systemic nor pulmonary hemodynamics were changed. Lung water content expressed as blood-free wet-to-dry weight ratio increased from 4.31 +/- 0.23 to 5.35 +/- 0.26 (p less than 0.05). Histological examinations revealed in many cases diffuse congestion of lungs and interstitial edema. These results suggest that VX injection induces an increase in pulmonary capillary permeability which may lead to a high-permeability edema. PMID- 1916076 TI - Toxicity of organophosphate nerve agents and related phosphonylated oximes compared to their anticholinesterase activity in neuron cultures. AB - Oximes, such as pralidoxime and toxogonin, are important therapeutic agents for the treatment of organophosphate (OP) nerve agent poisoning. Oximes can react with these nerve agents to give intermediates, phosphonylated oximes, which may be equally toxic to the parent OP. The sc LD50s of a series of phosphonylated 2 butanone and 2,3-butanedione monoximes were compared to the sc LD50s of their parent OPs (tabun, sarin, and VX) in CD-1 mice. In every case the derivatives were significantly less toxic than their parent nerve agents. Times to death, and to signs of poisoning, were inversely proportional to the dose of test compound, and in all mortalities, blood serum acetylcholinesterase (AChE) was severely inhibited. The relative potencies of these compounds, as well as soman, cyclohexyl methylphosphonofluoridate, and diisopropyl fluorophosphate, as inhibitors of AChE in primary cultures of mouse embryo neurons, correlated with their in vivo toxicities. The results indicate that mouse embryo neuron cultures may be a useful model with which to study this class of compounds. PMID- 1916077 TI - Muscarinic receptors and mucus secretion in swine tracheal epithelium: effects of subacute organophosphate treatment. AB - This swine trachea study was undertaken to examine the effects of nerve agents on mucus gland cell function. Subacute treatment of swine with soman, sarin, and VX inhibits acetylcholinesterase and leads to down-regulation of muscarinic receptors in tracheal submucosal gland cells. Muscarinic receptor density in isolated cells as determined by [3H]QNB binding was reduced by 60-65% and that measured using [3H]NMS was decreased by 65-73%. Subacute treatment of swine for 7 days with soman and VX caused a small, significant increase in the fraction of receptors with high affinity for carbachol. The decrease in receptor density was accompanied by a decrease in acetylcholine-induced mucus secretion. The decrease in mucus secretion was not due to a decrease in the ability of the cells to produce or release mucus since cross-tolerance did not develop to methoxamine induced mucus secretion. Therefore, we conclude that in mucus gland cells tolerance development can be linked functionally to muscarinic receptor loss. PMID- 1916078 TI - Metabolism of glyphosate in Sprague-Dawley rats: tissue distribution, identification, and quantitation of glyphosate-derived materials following a single oral dose. AB - Five groups of male Sprague-Dawley rats were orally administered a mixture of [14C]- and [12C]-glyphosate (N-phosphonomethylglycine) at a dose level of 10 mg/kg body weight. The majority of radioactivity 2 hr after administration was associated with the gastrointestinal contents and small intestinal tissue. Approximately 35-40% of the administered dose was absorbed from the gastrointestinal tract, and urine and feces were equally important routes of elimination. The total body burden 7 days after administration was approximately 1% of the administered dose and was primarily associated with the bone. Total recovery for this study ranged from 95 to 102% of the administered dose. Metabolic profiles of tissues containing greater than 1% of the administered dose at various times after administration indicated that nearly 100% of the body burden of radioactivity was present as unmetabolized parent glyphosate. A minor component constituting less than 0.1% of the administered dose (less than 0.4 ppm) was observed in colon tissue from animals 2 hr after the administration of glyphosate and was also present in the GI contents of one animal 28 hr after administration of the radiolabel. The retention time for this metabolite was similar, but not identical, to the retention time for AMPA (aminomethylphosphonic acid), the major bacterial metabolite of glyphosate found in soil. Tissue extraction efficiency was always greater than 90% and stability assays indicated no significant effect of storage on either parent glyphosate or AMPA. The results from this study indicate that virtually no toxic metabolites of glyphosate were produced since there was little evidence of metabolism and essentially 100% of the body burden was parent compound with no significant persistence of material. PMID- 1916079 TI - Chronic exposure to a simulated urban profile of ozone alters ventilatory responses to carbon dioxide challenge in rats. AB - Male Fischer 344 rats were exposed to a simulated urban profile of ozone (O3) (9 hr ramped spike, integrated concentration = 0.19 ppm) for up to 78 weeks. Small, but statistically significant, changes in breathing patterns and mechanics in unanesthetized, restrained rats were observed at Weeks 1, 3, 13, 52, and 78 during postexposure challenge with 0, 4, and 8% carbon dioxide (CO2). The data indicate that O3 exposure caused an overall increase in expiratory resistance (Rc), but particularly at 78 weeks. This increase in Rc most likely accounts for the rats' reduced ability to increase ventilation during CO2 challenge compared to control rats. Reductions in CO2-induced tidal volume increases were observed in all O3-exposed animals during postexposure challenges to 4 and 8% CO2. Cumulatively, over all time points, spontaneous frequency of breathing and CO2 induced hyperventilation were also reduced. The decrease in frequency was dependent on a significant increase in the inspiratory time relative to control without a change in expiratory time. Light microscopic evaluation of the lung did not reveal any lesions associated with O3 exposure at any time point. Although statistically significant effects were detected, the etiology of the above mentioned functional changes remains speculative. The potential relevance of these data to acute and chronic O3 exposure in humans is also discussed. PMID- 1916080 TI - Modulation of interleukin-2-driven proliferation of human large granular lymphocytes by carbaryl, an anticholinesterase insecticide. AB - Studies in other laboratories have provided evidence that the interleukin-2 (IL2) signaling pathway in lymphocytes includes essential, serine proteases. Since the anticholinesterase (antiCHE) insecticides are potent serine hydrolase (esterase and protease) inhibitors, we assessed the ability of carbaryl (CA, a widely used antiCHE insecticide) and alpha-naphthol (NA, a major metabolite of carbaryl) to modulate IL2-driven proliferation of large granular lymphocytes (LGL) purified from human peripheral blood. These cells express nearly all of the natural killer (NK) activity of human peripheral blood. NK cells are normal lymphocytes that respond to IL2 by proliferating and increasing their tumoricidal activity on a per cell basis. Cultures of purified LGL, initiated in the presence of human recombinant IL2, were harvested on culture Day 4, then proliferation was measured as [3H]thymidine incorporation. When added only at the time cultures were initiated. CA inhibited incorporation 10-32%, 35-53%, and 54-57% at 0.5, 5.0, and 50 microM, respectively. In contrast, NA had no effect at 0.5 and 5.0 microM, but was inhibitory (16-17%) at 50 microM. Reexposure to CA or NA, during the incorporation assay, had little effect on the observed inhibition profiles. Chemically induced changes in cell number during an 8-day culture period reflect the chemically induced changes in [3H]thymidine incorporation. Neither CA nor NA produced cell death. Quantitation of both CA and NA by HPLC indicated a rapid loss of CA (ca. 95% in 24 hr) and a much slower loss of NA from the culture medium. CA inhibited human LGL proliferation at concentrations producing little or no inhibition of serum CHE, an indicator of exposure to antiCHE insecticides. PMID- 1916081 TI - Investigations of amitraz neurotoxicity in rats. IV. Assessment of toxicity syndrome using a functional observational battery. AB - A Functional observational battery (FOB) was utilized to provide a semiquantitative description of the hyperreactivity, excitability, and debilitation produced by amitraz. Adult male Long-Evans rats were administered either vehicle or 10, 25, 50, 100, or 200 mg/kg amitraz ip. They were tested with the FOB immediately before dosing, at 1 and 4 hr, and at 1, 2, 4, and 8 days after dosing. Higher doses (100-200 mg/kg) produced increased reactivity to manipulation, tenseness, and aggression. Most or all doses produced depressed arousal and rearing activity, hypothermia, body weight loss, and autonomic changes including ptosis, chromodacryorrhea resulting in facial crustiness, loss of the pupil reflex, and decreased defecation. Altered gait and decreased landing foot splay were also produced by amitraz. For the most part, effects of lower doses (10-50 mg/kg) were reversible by 2 to 4 days after treatment. In the higher dose groups, however, signs of toxicity were evident, and in some cases even more prominent (e.g., handling hyperreactivity), 8 days after a single dose of amitraz. The FOB thus provided a semiquantitative description of the magnitude and time course of many features of the amitraz toxicity syndrome. PMID- 1916082 TI - Early effects of lead on bone marrow cell responsiveness in mice challenged with Listeria monocytogenes. AB - Listeria monocytogenes challenge of lead-treated mice results in increased mortality. Since macrophage development constitutes the initial phase of the immune response to L. monocytogenes, bone marrow and spleens from Pb-treated mice that were infected with L. monocytogenes were analyzed for their ability to form colonies when exposed to the macrophage growth factor CSF-1. Serum colony stimulating activity also was evaluated. Data obtained indicate the Pb exposure results in decreased responsiveness of bone marrow and spleen cells to CSF-1 while colony-stimulating activity in serum rises. This lack of bone marrow derived macrophage development may contribute to the increased mortality observed with L. monocytogenes challenged. Pb-treated mice. PMID- 1916083 TI - Rapid administration of high-dose human antibody Fab fragments to dogs: pharmacokinetics and toxicity. AB - The treatment of drug overdose with drug-specific antibody fragments may require very high antibody doses. To address the feasibility of this therapy, we studied the pharmacokinetics and toxicity of high-dose human nonspecific Fab fragments in beagles. Three dogs received 5.3 g/kg Fab iv over 1 hr. Because nephrotoxicity was observed, three subsequent dogs received 3.2 g/kg. The fraction of the Fab dose excreted in urine (10 +/- 6%) was lower than reported values for either high or low doses of Fab in other species. The terminal serum elimination half-life (42 hr for the higher and 48 hr for the lower dose) was also longer than reported values for other species, due to lower renal and nonrenal Fab clearance. Fab administration was tolerated without adverse hemodynamic effects. One of three dogs at each dose developed transient oliguria. All dogs developed a transient but marked increase in the serum creatinine concentration. At 2 weeks creatinine clearance had returned to normal. Urinary protein and albumin excretion at 2 weeks were within the normal range for dogs but were increased over their baseline values. The histology of all organs was normal at 3 weeks by light microscopy, and renal histology by electron microscopy was also normal. The mechanism of Fab nephrotoxicity, not observed previously with high-dose Fab in rats or lower doses of Fab in other species including dogs, is not clear. These data suggest that further study of the potential toxicity of high-dose Fab, and its reversibility, is needed to assess the feasibility of treating drug overdose with this antibody fragment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916084 TI - Toxicity of 2,6-dichlorothiobenzamide (chlorthiamid) and 2,6-dichlorobenzamide in the olfactory nasal mucosa of mice. AB - The toxic effects of the herbicide chlorthiamid (2,6-dichlorothiobenzamide) and its major environmental metabolite 2,6-dichlorobenzamide (DCBA) were examined in the nasal passages of C57Bl mice following single ip injections. Chlorthiamid (12.25, and 50 mg/kg) induced an extensive destruction of the olfactory region, similar to that previously observed with the analogue dichlobenil (2,6 dichlorobenzonitrile). Necrosis of Bowman's glands was evident first, whereas degeneration and necrosis of the olfactory neuroepithelium developed less rapidly. The lesions were most severe in the dorsomedial region of the nasal cavity. At longer post-treatment intervals, the olfactory epithelium was replaced by a respiratory-like epithelium, and there was fibrosis of the lamina propria. DCBA was also toxic to the olfactory region (100 mg/kg), inducing necrosis of the Bowman's glands and the neuroepithelium in the dorsomedial region of the nasal cavity. No lesions were observed in other parts of the nasal cavity or in the liver after administration of chlorthiamid or DCBA. Chlorthiamid (IC50 = 51 microM), but not DCBA, inhibited the covalent binding of 14C-labeled dichlobenil in the olfactory mucosa in vitro. It is proposed that the toxic effects of chlorthiamid and dichlobenil in the olfactory mucosa are mediated by common or closely related metabolites. PMID- 1916085 TI - Indirect costs: FASEB looks for the answers. PMID- 1916086 TI - Consensus conference on indirect costs. PMID- 1916087 TI - Analysis of SBIR phase I and phase II review results at the National Institutes of Health. AB - A cohort of phase I and phase II summary statements for the SBIR grant applications was evaluated to determine the strengths and weaknesses in approved and disapproved applications. An analysis of outcome variables (disapproval or unfunded status) was examined with respect to exposure variables (strengths or shortcomings). Logistic regression models were developed for comparisons to measure the predictive value of shortcomings and strengths to the outcomes. Disapproved phase I results were compared with an earlier 1985 study. Although the magnitude of the frequencies of shortcomings was greater in the present study, the relative rankings within shortcoming class were more alike than different. Also, the frequencies of shortcomings were, with one exception, not significantly different in the two studies. Differences in the summary statement review may have accounted for some differences observed between the 1985 data and results of the present study. Comparisons of Approved/Disapproved and Approved Unfunded/Funded yielded the following observations. For phase I applicants, a lack of a clearly stated, testable hypothesis, a poorly qualified or described investigative team, and inadequate methodological approaches contributed significantly (in that order) to a rating of disapproval. A critical flaw for phase II proposals was failure to accomplish objectives of the phase I study. Methodological issues also dominate the distinctions in both comparison groups. A clear result of the data presented here and that published previously is that SBIR applicants need continuing assistance to improve the chances of their success. These results should serve as a guide to assist NIH staff as they provide information to prospective applicants focusing on key elements of the application. A continuing review of the SBIR program would be helpful to evaluate the quality of the submitted science. PMID- 1916088 TI - Compartmentation of folate-mediated one-carbon metabolism in eukaryotes. AB - Folate coenzymes supply the activated one-carbon units required in nucleic acid biosynthesis, mitochondrial and chloroplast protein biosynthesis, amino acid metabolism, methyl group biogenesis, and vitamin metabolism. Because of its central role in purine and thymidylate biosynthesis, folate-mediated one-carbon metabolism has been the target of many anticancer drug therapies. This review is a summary of recent results that suggest that folate-mediated one-carbon metabolism is highly compartmentalized in eukaryotic cells. Evidence exists for compartmentation of folate coenzymes and their one-carbon units between intracellular organelles, for substrate channeling of folate coenzymes, and for compartmentation by intracellular folate-binding proteins. Metabolic, regulatory, and therapeutic implications of these processes are discussed. PMID- 1916089 TI - Gram-negative endotoxin: an extraordinary lipid with profound effects on eukaryotic signal transduction. AB - The lipid A domain of lipopolysaccharide (LPS) is a unique, glucosamine-based phospholipid that makes up the outer monolayer of the outer membrane of most gram negative bacteria. Because of its profound pharmacological effects on animal cells, especially those of the immune system, lipid A is also known as endotoxin. Despite decades of earlier work, the precise chemistry of endotoxins and the biochemical pathways for their enzymatic synthesis have been elucidated only within the past 5 years. In this review, we summarize the essentials of endotoxin biochemistry and also present recent experiments aimed at identifying surface receptors, signal-transducing elements, transcriptional factors, and key intracellular targets involved in the response of animal cells to endotoxins. PMID- 1916090 TI - Nutritional requirements for boron, silicon, vanadium, nickel, and arsenic: current knowledge and speculation. AB - Definition of specific biochemical functions in higher animals (including humans) for the ultratrace elements boron, silicon, vanadium, nickel, and arsenic still has not been achieved although all of these elements have been described as being essential nutrients. Recently, many new findings from studies using molecular biology techniques, sophisticated equipment, unusual organisms, and newly defined enzymes have revealed possible sites of essential action for these five elements. Based on these findings and the response of animals and/or humans to low intakes of these elements, the following speculations have been presented: 1) Boron has a role that affects cell membrane characteristics and transmembrane signaling. 2) Silicon is necessary for the association between cells and one or more macromolecules such as osteonectin, which affects cartilage composition and ultimately cartilage calcification. 3) Vanadium reacts with hydrogen peroxide to form a pervanadate that is required to catalyze the oxidation of halide ions and/or stimulate the phosphorylation of receptor proteins. 4) Nickel is needed for the CO2-fixation to propionyl-CoA to form D-methylmalonyl-CoA. 5) Arsenic has an important role in the conversion of methionine to its metabolites taurine, labile methyl, and the polyamines. If any of these speculations are found to be true, the element involved will be firmly established as having a nutritional requirement because the body obviously cannot synthesize it. Based on animal findings, the dietary requirement is likely to be small; that is, expressed in micrograms per day. PMID- 1916091 TI - Structure and function of A1 adenosine receptors. AB - The A1 adenosine receptor is the best characterized of the widely distributed purinergic receptor family. The purified brain A1 receptor is a monomeric 35- to 36-kDa glycoprotein. A1 receptors can be clearly distinguished from A2 adenosine receptors on the basis of structure activity relationships with selective ligands. Recent structure activity data suggest that subtypes of A1 (A1a, A1b, and A3) and A2 (A2a and A2b) receptors may exist. A1 receptor-mediated responses are coupled via multiple pertussis toxin-sensitive GTP binding proteins (G proteins) to many different effectors in various tissues: adenylate cyclase, phospholipase C, Na+- Ca2+ exchange, Ca2+ channels, Cl- channels, and K+ channels. The formation of calcium-mobilizing inositol phosphates can either be enhanced or inhibited. In general, adenosine has been found to act in concert with other hormones or neurotransmitters in either an inhibitory or a stimulatory way. The myriad modulatory actions of adenosine suggest that: 1) adenosine may simultaneously produce multiple effects within the same cell; and 2) activation of A1 receptors may lead to either a decrease or an increase in the coupling of other receptors to their G proteins. PMID- 1916092 TI - Fc receptors and immunoglobulin binding factors. AB - Receptors for the Fc portion of Ig (Fc receptors, FcR) are found on all cell types of the immune system. Three types of FcR react with IgG: Fc gamma RI is a high-affinity receptor binding IgG monomers whereas Fc gamma RII and Fc gamma RIII are low-affinity receptors binding IgG immune complexes; the three types of Fc gamma R are members of the Ig superfamily. Two FcR react with IgE:Fc epsilon RI is a multichain receptor binding IgE with high affinity; it is composed of an IgE-binding alpha chain, homologous to Fc gamma RIII, and of gamma and beta chains that are necessary for receptor expression and signal transduction. The low-affinity Fc epsilon RII is the only FcR described so far that is not a member of the Ig superfamily but resembles animal lectins; it is composed of a transmembrane chain with an intracytoplasmic NH2 terminus. Fc alpha R has homology with Fc gamma R and is a member of the Ig superfamily. Receptors for IgM and IgD are not characterized yet. Finally, Ig transport is made by FcR-like molecules such as the poly-Ig receptor or an MHC-like receptor found on neonatal intestine. A remarkable property of most FcR is the fact that they are released in cell supernatants and circulate in biological fluids as immunoglobulin binding factors (IBF) generated either by cleavage at the cell membrane or by splicing of FcR transmembrane exon. Immunoglobulin binding factors may interfere with Ig mediated functions and have direct immunoregulatory activities. Involvement of FcR or IBF has been postulated in several diseases, and monoclonal antibodies to FcR are beginning to be used in therapeutics, particularly to target cytotoxic effector lymphocytes and monocytes to tumor cells. PMID- 1916094 TI - Endothelins. AB - The discovery of endothelium-derived relaxing (prostacyclin, EDRF) and contracting factors (EDCF) in the past decade opened up new vistas not only for basic and clinical research, but revolutionized our thinking about regulation and control of the cardiovascular system in health and disease. One of the most exciting developments in recent years was the discovery of a peptidergic EDCF and its isolation and identification as a unique 21-amino-acid peptide, endothelin (ET). This review summarizes the state-of-the-art in some areas of this fast moving field, including the biosynthesis, tissue-specific expression, and binding of ET isoforms. Recent information about the nature of endothelin-converting enzyme (ECE) and the cloning, sequencing, and expression of ET receptor subtypes will be discussed. Based on current knowledge of the wide variety of biological actions of ETs, working hypotheses are presented about the possible autocrine, paracrine, and humoral actions of ETs and their potential role in modulating cardiovascular functions. In addition, the proposed significance of ETs in human cardiovascular diseases is summarized. In spite of the abundance of studies generated over the past 3 years and the postulated working hypotheses based on these findings, the true significance of ETs in short- and long-term regulation/modulation of tissue function remains to be determined. This will be the task of future investigations, using more sensitive detection methods and selective inhibitors of the biosynthesis and actions of ETs. PMID- 1916093 TI - Staphylococcal enterotoxin microbial superantigens. AB - Staphylococcal enterotoxins are a family of structurally related proteins that are produced by Staphylococcus aureus. In addition to their role in the pathogenicity of food poisoning, these microbial superantigens have profound effects on the immune system, which makes them useful tools for understanding its mechanism of action. These molecules (24-30 kDa) are highly hydrophilic and exhibit low alpha helix and high beta pleated sheet content, suggesting a flexible, accessible structure. Staphylococcal enterotoxins are among the most potent activators of T lymphocytes known. The receptors for staphylococcal enterotoxins on antigen-presenting cells are major histocompatibility complex (MHC) class II molecules. Further, the alpha-helical regions of the class II molecule are essential for function and appear to interact directly with the NH2 terminal region of staphylococcal enterotoxins such as SEA. Recent studies have shown that a complex of staphylococcal enterotoxin and MHC class II molecules is required for binding to the V beta region of the T cell antigen receptor. Staphylococcal enterotoxin mitogenic activity is dependent on induction of interleukin 2, which may be intimately involved in the mechanism of toxicity. The mouse minor lymphocyte stimulating (M1s) "endogenous" self-superantigen has been shown to be a retroviral gene product, so this too is apparently a microbial superantigen. An understanding of the mechanisms of action of these microbial superantigens has implications for normal and pathological immune functions. PMID- 1916095 TI - Human liver cocaine esterases: ethanol-mediated formation of ethylcocaine. AB - A new, pharmacologically active metabolite of cocaine, ethylcocaine, has been reported in individuals after concurrent use of cocaine and ethanol. Formation of ethylcocaine may contribute to the common coabuse of these two drugs and the apparent danger of this practice. We have identified a nonspecific carboxyl esterase that catalyzes the ethyl transesterification of cocaine to ethylcocaine in the presence of ethanol. In the absence of ethanol, this human liver esterase catalyzes the hydrolysis of cocaine to benzoylecgonine, a metabolite that is inactive as a psychomotor stimulant. A second human liver esterase is also described. This enzyme catalyzes hydrolysis of cocaine to ecgonine methyl ester, also inactive as a stimulant. These two liver esterases may play important roles in regulating the metabolic inactivation of cocaine. PMID- 1916096 TI - The golden age of Federation meetings: 1936-1942. PMID- 1916098 TI - Good science in the newly emerging European democracies. PMID- 1916097 TI - Research funding. PMID- 1916099 TI - Nutritional sciences: opportunities with expanding biosciences. PMID- 1916100 TI - State-of-the-art biomolecular core facilities: a comprehensive survey. AB - A survey of 124 protein and/or nucleic acid chemistry facilities has provided a basis for estimating the resources needed to establish a facility, the financial support needed to keep it operating, and the technical capabilities it might reasonably be expected to achieve. Based on these data, an average core facility occupied 870 ft2, was staffed by three full-time personnel, and was equipped with 4-5 major instrument systems. Because user fees generated an average of about $101,000/year in income compared with an average operating budget of about $197,000/year, even a facility that charged user fees would, on average, still require an annual subsidy of about $96,000. Although most government and industrial core facilities did not assess user fees, at least 83 of the 124 respondents did have a preestablished schedule of service charges that enabled a compilation to be made of the average cost of providing a number of typical facility analyses and syntheses. The greater than 100-fold range in charges assessed in core facilities for seemingly identical services was shown to result from the equally large range in the degree of subsidization of these laboratories. Although an average facility might be expected to offer four or five of the following six major services--amino acid sequencing, amino acid analysis, HPLC peptide isolation, peptide synthesis, fragmentation of proteins and DNA synthesis--less than 10% of the responding laboratories provided mass spectrometry, capillary zone electrophoresis, or RNA synthesis. With the exception of peptide synthesis, which had an average turn-around time of about 24 days, all other major services had turn-around times that averaged in the range of 4-9 days. Additional data are summarized regarding average sample throughput in core laboratories and the amount of protein that is needed for hydrolysis/amino acid analysis and sequencing. PMID- 1916101 TI - Dietary fat: exogenous determination of membrane structure and cell function. AB - Evidence indicates that principal features of the membrane involve structural organization of lipids in the form of a bilayer with functional proteins either bound to the bilayer surface or inserted into the bilayer and interacting within specific domains in the lipid milieux. In homeotherms, intrinsic and extrinsic factors apparently form the basis for determination of membrane lipid composition and thus membrane physicochemical properties. Moreover, many intrinsic metabolic controls, such as fatty acid desaturation and phospholipid biosynthesis, may be attenuated by change in the nature of the extrinsic or dietary influence. This review will focus on the role of dietary fat as a determinant of subcellular structural constituents to illustrate that feeding nutritionally adequate diets differing in fatty acid composition can induce physiological transitions in membrane function involving the activity of enzymes responsible for synthesis of membrane constituents, hormone-activated functions and expression of activity in the cell nucleus. PMID- 1916102 TI - Antigen presentation in acquired immunological tolerance. AB - In acquired tolerance, previous exposure to antigen under certain conditions induces specific unresponsiveness instead of specific immunological memory. It has been studied as an approach to the mechanisms of self-tolerance that operate on immunocompetent T and B lymphocytes once they leave their sites of origin in the thymus and the bone marrow. Possible mechanisms involve induction of specific suppressor cells or inactivation of antigen-specific lymphocytes (clonal anergy) as a consequence of abortive antigen presentation, in which the antigen receptor is effectively engaged but certain poorly defined accessory signals the T lymphocytes require are lacking. We propose that small, resting B lymphocytes, which lack these accessory signals, are the inactivating antigen-presenting cells in acquired tolerance to proteins and to the class II transplantation antigens. B lymphocytes, which can use their antigen receptors to gather and process antigens that are present at very low concentrations, may play a role in self-tolerance. In addition, B lymphocytes and T lymphocytes rendered anergic by encounter with self antigens could persist as self-specific suppressor cells to block an autoimmune response of autoreactive clones that had escaped deletion or anergy. PMID- 1916103 TI - Protein transport across the endoplasmic reticulum membrane: facts, models, mysteries. AB - The first step in the biosynthesis of secretory proteins, plasma membrane proteins, and many other proteins in a eukaryotic cell involves the transport of at least portions of the polypeptides across the endoplasmic reticulum (ER) membrane. Parts of the polypeptide chains serve as signals that direct the translocation across and the integration into the ER membrane and also determine the orientation of membrane proteins. The transport process itself may be divided into two phases: an initiation or targeting cycle, which is fairly well understood, and the actual transfer of the polypeptide chain through the membrane, the mechanism of which is still mysterious. The initiation cycle generally involves the function of the signal recognition particle (SRP) which binds to signal sequences through its 54-kDa polypeptide component, and of the SRP-receptor (docking protein) in the ER membrane whose function is dependent on GTP. The membrane transfer of the polypeptide chain appears to involve a translocation complex consisting of several membrane proteins, one of which is the signal sequence receptor protein (SSR). PMID- 1916105 TI - Collagen family of proteins. AB - Collagen molecules are structural macro-molecules of the extracellular matrix that include in their structure one or several domains that have a characteristic triple helical conformation. They have been classified by types that define distinct sets of polypeptide chains that can form homo- and heterotrimeric assemblies. All the collagen molecules participate in supramolecular aggregates that are stabilized in part by interactions between triple helical domains. Fourteen collagen types have been defined so far. They form a wide range of structures. Most notable are 1) fibrils that are found in most connective tissues and are made by alloys of fibrillar collagens (types I, II, III, V, and XI) and 2) sheets constituting basement membranes (type IV collagen), Descemet's membrane (type VIII collagen), worm cuticle, and organic exoskeleton of sponges. Other collagens, present in smaller quantities in tissues, play the role of connecting elements between these major structures and other tissue components. The fibril associated collagens with interrupted triple helices (FACITs) (types IX, XII, and XIV) appear to connect fibrils to other matrix elements. Type VII collagen assemble into anchoring fibrils that bind epithelial basement membranes and entrap collagen fibrils from the underlying stroma to glue the two structures together. Type VI collagen forms thin-beaded filaments that may interact with fibrils and cells. PMID- 1916104 TI - Prions and prion proteins. AB - Neurodegenerative diseases of animals and humans including scrapie, bovine spongiform encephalopathy, and Creutzfeldt-Jakob disease are caused by unusual infectious pathogens called prions. There is no evidence for a nucleic acid in the prion, but diverse experimental results indicate that a host-derived protein called PrPSc is a component of the infectious particle. Experiments with scrapie infected cultured cells show that PrPSc is derived from a normal cellular protein called PrPC through an unknown posttranslational process. We have analyzed the amino acid sequence and posttranslational modifications of PrPSc and its proteolytically truncated core PrP 27-30 to identify potential candidate modifications that could distinguish PrPSc from PrPC. The amino acid sequence of PrP 27-30 corresponds to that predicted from the gene and cDNA. Mass spectrometry of peptides derived from PrPSc has revealed numerous modifications including two N-linked carbohydrate moieties, removal of an amino-terminal signal sequence, and alternative COOH termini. Most molecules contain a glycosylinositol phospholipid (GPI) attached at Ser-231 that results in removal of 23 amino acids from the COOH terminus, whereas 15% of the protein molecules are truncated to end at Gly-228. The structure of the GPI from PrPSc has been analyzed and found to be novel, including the presence of sialic acid. Other experiments suggest that the N linked oligosaccharides are not necessary for PrPSc formation. Although detailed comparison of PrPSc with PrPC is required, there is no obvious way in which any of the modifications might confer upon PrPSc its unusual physical properties and allow it to act as a component of the prion. If no chemical difference is found between PrPC and PrPSc, then the two isoforms of the prion protein may differ only in their conformations or by the presence of bound cellular components. PMID- 1916106 TI - Lactose intolerance and the genetic regulation of intestinal lactase-phlorizin hydrolase. AB - Lactase-phlorizin hydrolase, which hydrolyzes lactose, the major carbohydrate in milk, plays a critical role in the nutrition of the mammalian neonate. Lactose intolerance in adult humans is common, usually due to low levels of small intestinal lactase. Low lactase levels result from either intestinal injury or (in the majority of the world's adult population) alterations in the genetic expression of lactase. Although the mechanism of decreased lactase levels has been the subject of intensive investigation, no consensus has yet emerged. Recent studies have begun to define the cellular and molecular biology of this enzyme. In animals and humans, a glycosylated precursor is proteolytically cleaved to yield the mature enzyme on the microvillus membrane of the enterocyte, bound to the lipid bilayer only by a hydrophobic anchor sequence. The enzyme hydrolyzes lactose, phlorizin, and glycosylceramides. A decline in lactase specific activity occurs at the time of weaning in most mammalian species; in most humans who have low lactase activity as adults, the decline occurs at approximately 3-5 years of age. In a few human groups, the elevated juvenile level of lactase specific activity persists throughout adulthood. These developmental patterns of lactase expression are most likely regulated at the level of gene transcription. PMID- 1916107 TI - RNA polymerase: regulation of transcript elongation and termination. AB - Expanded interest in studying the mechanisms of elongation and termination during transcription has come as a result of several recent findings that highlight the importance of the regulation of these processes in human health. Several cellular proto-oncogenes contain regulated blocks to elongation (1), and the human immunodeficiency viruses also control gene expression in part by regulating the efficiency of elongation in response to the trans-activating protein, TAT (2). This review considers these recent findings and compares potential mechanisms of regulation used by prokaryotic and eukaryotic RNA polymerases during elongation and termination. In all these systems, many of the detailed mechanisms of transcription elongation and termination are still to be defined; however, we have tried to group examples that may share some common regulatory elements into simplified categories. PMID- 1916108 TI - Computer-aided mechanogenesis of skeletal muscle organs from single cells in vitro. AB - Complex mechanical forces generated in the growing embryo play an important role in organogenesis. Computerized mechanical application of similar forces to differentiating skeletal muscle myoblasts in vitro generate three-dimensional artificial muscle organs. These organs contain parallel networks of long unbranched myofibers organized into fascicle-like structures. Tendon development is initiated and the muscles are capable of performing directed, functional work. Kinetically engineered organs provide a new method for studying the growth and development of normal and diseased tissue. PMID- 1916110 TI - Integrity of scientific enterprises. PMID- 1916111 TI - Posters at scientific meetings in the United States. PMID- 1916109 TI - Isotope time--50 years ago. PMID- 1916112 TI - [Gastric acidity inhibition. Consequences on N-nitrosocompounds-induced gastric carcinogenesis]. PMID- 1916113 TI - [Effects of gastric acid secretion inhibition on intrinsic factor secretion and cobalamin absorption]. PMID- 1916114 TI - [How to quantify argyrophil (enterochromaffin-like cells) cells in the fundus mucosa?]. PMID- 1916115 TI - [Effect of endogenous and exogenous gastrin on enterochromaffin-like cell proliferation]. PMID- 1916116 TI - [Fundic endocrine disease of fundic atrophic gastritis with achlorhydria. I- Serum gastrin and fundic endocrine hyperplasia relationship. Reality and significance]. PMID- 1916117 TI - [Fundic endocrinopathy in fundic atrophic gastritis with achlorhydria. II- Carcinoid tumors]. PMID- 1916118 TI - [Anomalies of fundic argyrophil cell proliferation (enterochromaffin-like cells) in Zollinger-Ellison syndrome]. PMID- 1916119 TI - [Effects of antisecretory therapy on serum gastrin and argyrophil cells of the fundus mucosa]. PMID- 1916120 TI - [From acid secretion inhibition to enterochromaffin-like cell proliferation. Traps on the path]. PMID- 1916121 TI - [Anomalies of serum gastrin secretion in digestive pathology]. PMID- 1916123 TI - [Biomedical research and Huriet's law: revival or recession of clinical research?]. PMID- 1916122 TI - [Gastric anacidity. Effects on gastrointestinal microflora and physiopathological consequences]. PMID- 1916124 TI - [Significance of isolated anti-HBs antibodies in subjects not vaccinated against hepatitis B viruses]. AB - The significance of isolated anti-HBs antibodies in subjects not vaccinated against the hepatitis B virus (HBV) was investigated in 13 healthy blood donors. All were European and none had any risk factor for hepatitis B infection. Serological assays included HBV-DNA and anti-preS 2 antibody determinations which were all negative. After injection with hepatitis B vaccine (Hevac B), only one out of the 13 subjects exhibited an anamnestic response in favor of secondary immunization. Neutralization tests for serum anti-HBs antibody were positive in only 6 subjects. Our data suggest that in most cases isolated anti-HBs positivity does not correspond to true antibody; booster injection of HBV vaccine seems to be the best way of verifying that antibodies are really protective. PMID- 1916125 TI - [How to express the percentage of words expressing the frequency (or sensitivity) of symptoms in a disease?]. AB - A prospective multicenter study concerning 30 vocabulary terms was undertaken to determine if: 1) these terms could be equated with specific percentages; 2) observer assessment varied with time; 3) teachers and students used the same words with the same meaning; 4) certain words were more discriminant than others, and 5) terms corresponding to numbers were the same in French as in English. Three hundred and thirty medical professionals, coming from general and digestive units of 45 University, regional, or private institutions, were asked to answer three types of questionnaires pertaining to the same 30 words, but in a different order. One to 3 months later, 170 of them were asked to fill out the same questionnaire with the same words but in a different order. Sixteen percent were University professors, 15 percent were hospital or private surgeons, 19 percent were senior residents, 29 percent were interns or junior residents and 21 percent were medical students.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916126 TI - [Molecular biology of hepatitis B virus. I: Structure, genetic organization, replication, transcription]. PMID- 1916127 TI - [Molecular biology of the hepatitis B virus. II: Importance of the detection of DNA of the hepatitis B virus in serum and liver]. PMID- 1916128 TI - [Severe dysplasia of the esophagus: what should be done?]. PMID- 1916129 TI - [Collis's operation for brachyesophagus. (49 patients)]. AB - The results of infradiaphragmatic Collis' gastroplasty for the treatment of gastroesophageal reflux associated with acquired short brachyesophagus (Barrett's esophagus) were prospectively studied in 49 patients (50 operations). Clinical and endoscopic findings, and 3-hour postprandial pH measurement including Kaye's score were evaluated at short (3 to 8 months), medium (1 to 4 years), and long term (more than 4 years) for all patients. Postoperative morbidity was 16 percent; there were 3 deaths (6 percent). Short term results, evaluated in 45 patients, were considered satisfactory in 30, poor (pyrosis and esophagitis) in 2, and incomplete (pyrosis without esophagitis in 2, dysphagia in 5, mild esophagitis in 6) in 13. Long term results (32 patients) were satisfactory in 24, poor in 5, and incomplete in 3 (pyrosis without esophagitis in one, gastric outlet disorder in 2). Long term pH measurements were obtained in 21 patients: 3 out of 6 patients with high scores had clinical or endoscopic signs of esophagitis. Analysis of late results showed that: a) satisfactory short term outcome was maintained in all but 2 patients (deterioration was observed in one patient 4 years later because of aggressive treatment for terminal bronchopulmonary carcinoma; the other was observed 5 years later after steroid therapy for aspergilloma with severe asthma); b) pH scores were variable in 11 patients. This variability and discordance of pH measurements was most likely due to the presence of acid secretion above the new esogastric junction, which was observed in half of the cases. We conclude that Collis' gastroplasty provided good results in Barrett's esophagus and might be compared to duodenal diversion in ulterior studies in this setting. PMID- 1916130 TI - [Effect of gastrin and enprostil, a PGE2 analog, on colonic cancerous cell growth]. AB - The effects of gastrin (G-17), proglumide (a gastrin receptor antagonist), and enprostil (a synthetic analog of prostaglandin E2) used alone or in association were studied in colonic cancer Prob and Regb cell growth. The Prob (progressive in BD IX rats) and Regb (regressive) cell lines were cloned from a single chemically-induced rat colonic cancer. After a serum-free period corresponding to one doubling cell time, cells were incubated with 100 to 1,200 pM G-17, 40 or 80 mM proglumide, and 2.5 to 5 micrograms/ml enprostil for 8 h. Cell growth was measured 48 h later by colorimetric MTT assay. Two and four hundred pM G-17 gave a growth stimulation of 17.4 percent and 31 percent for Prob cells respectively or 35.5 percent and 49 percent for Regb cells. Growth stimulation was found to be statistically different (P less than 0.01) for Prob and Regb cells. Proglumide partially inhibited this growth stimulation whereas enprostil inhibited in totally. These results suggest that growth of some colonic cancer cell lines may be G-17 dependent. However the intensity of cell-growth stimulation depends on the level of cell malignancy or differentiation in a single tumor. PMID- 1916131 TI - [Immunochemical evidence of a mutated p53 protein expressed in human colorectal adenocarcinoma]. AB - Evidence is accumulating that the p53 anti-oncogene is a key gene in the genesis of carcinoma in human colon and rectum. Although mutations of the p53 gene have been shown to be frequent, the protein was present in only approximately 50 percent of specimens examined. However only one monoclonal antibody recognizing an epitope present on wild-type p53 had been used. We studied the p53 expression in a series of 16 colorectal carcinoma specimens using 3 different monoclonal antibodies (pAb 421, 1801, 240). Specific immunofluorescent staining was quantified by dual parameter (DNA/p53) flow cytometry. Two different types of preparations were compared in order to verify the conservation of the antigen. Nuclear suspensions prepared from frozen tumor fragments were shown to produce results equivalent to those of whole cell preparations originating from fresh surgical specimens. The p53 protein was detected in 9 of the 16 cancers with pAb 421 and 240 monoclonal antibodies (8 of which were also positive for pAb 1801 antibody). Four additional tumors were considered positive for pAb 240 antibody alone. Overall, 13/16 cancer specimens were shown to present immunoreactivity for pAb 240 antibody. Topography of staining was investigated by immunohistochemistry with peroxidase methods. Eight cases were informative, 6 of which presented nuclear staining compatible with the cytometry results. There was one discordant case i.e. pAb 240 antibody being positive on cytometry and entirely negative on immunohistochemistry. This small series allowed us to show that 81 percent of tumor samples stained with monoclonal antibody pAb 240, considered to be specific to mutated protein, and that some tumors express a p53 protein which is not detected with terminal sequence-specific antibodies. PMID- 1916132 TI - [Jejunal secretion of immunoglobulins and secretory component in three patients with primitive humoral immunoglobulin deficiency]. AB - Jejunal secretion of albumin, immunoglobulins and secretory component was studied using the segmental perfusion technique with an occluding balloon, in two patients with common variable hypogammaglobulinemia and one patient with selective immunoglobulin A deficiency. Results were compared with those of twenty two controls previously studied under the same conditions. In all three cases, jejunal secretion rate of immunoglobulin A was nil and secretion rates of albumin and immunoglobulin G were increased as compared to controls. Jejunal secretion rate of immunoglobulin M was increased in the patient with selective immunoglobulin A deficiency, normal in one case of common variable hypogammaglobulinemia and almost nil in the other case. Secretory component was secreted in the jejunal lumen mostly or exclusively under a free form depending on partial or total absence of immunoglobulin A and M. This study allowed to confirm in vivo that secretion of secretory component is independent of the presence of immunoglobulins. Intestinal perfusion might be a useful tool in the investigation of immunological diseases of the intestinal tract. PMID- 1916133 TI - [External adjuvant radiation therapy in rectal cancers. Analysis and results of randomized trials]. PMID- 1916135 TI - [Liver lipogranulomas with log-term fever caused by paraffin oil]. AB - In hepatic granuloma, identification of lipogranulomas generally leads to etiological diagnosis. The case reported here was granulomatosis due to mineral oil ingestion, revealed by prolonged fever. In the literature lipogranulomas are generally asymptomatic and diagnosed at autopsy. PMID- 1916134 TI - [Diaphragm of inferior vena cava associated with Budd-Chiari syndrome. Contribution of ultrasonography and color Doppler echocardiography]. AB - We report the case of a young man presenting clinical features of portal hypertension of unknown origin. The ultrasonographic examination showed suprahepatic blockage signs leading to the diagnosis of Budd-Chiari syndrome caused by incomplete diaphragm of the inferior vena cava. The color Doppler examination suggested caval obstruction, showing an abrupt shift from a laminar to a bosterous flux. Secondly cavograms and surgery later confirmed the diagnosis. PMID- 1916136 TI - [Caustic esophago-gastric and liver lesions caused by ingestion of a plastic resin hardener]. PMID- 1916138 TI - [Mirizzi's syndrome secondary to cystic lithiasis. Treatment with endoscopic sphincterotomy]. PMID- 1916137 TI - [Intrahepatic bile duct dilatation and cholestatic viral hepatitis A]. PMID- 1916139 TI - [Nilutamide-induced acute hepatitis]. PMID- 1916140 TI - Helicobacter pylori density on antral mucosa of patients with and without duodenal ulceration. PMID- 1916141 TI - [Diffuse colonic adenocarcinoma in the course of ulcerative colitis]. PMID- 1916142 TI - [Acute colonic pseudo-obstruction (Ogilvie's syndrome): treatment with cisapride]. PMID- 1916143 TI - [Vitamin D deficiency caused by exocrine pancreatic insufficiency complicating hemorrhagic rectocolitis]. PMID- 1916144 TI - Effect of erythromycin on gastroesophageal reflux. PMID- 1916145 TI - [Lymphoma and adenocarcinoma of the small intestine revealing celiac disease in adults]. PMID- 1916147 TI - [Pseudo-angina pain: coexistence of esophageal and coronary microcirculatory anomalies]. PMID- 1916146 TI - [Transient ischemic colitis complicating sickle cell crisis]. PMID- 1916148 TI - [Gastritis caused by spiral bacteria other than Helicobacter pylori: clinical, histological and ultrastructural study]. PMID- 1916149 TI - Effects of water-immersion-induced stress and intraperitoneal administration of brain-gut peptides upon immunoreactive thyrotropin-releasing hormone and prostaglandin E2 concentrations in the rat stomach. AB - The effects of water-immersion-induced stress and intraperitoneal (i.p.) administration of selected neuropeptides on the levels of thyrotropin-releasing hormone (TRH) and prostaglandin E2 (PGE2) were studied in the rat stomach. Water immersion caused a significant decrease immunoreactive-TRH (ir-TRH) concentrations in the stomach, and a significant increase in ir-TRH concentrations in the gastric juice. The concentrations of PGE2 were significantly increased at 0.5-4 hrs, and significantly decreased at 6-8 hrs after water-immersion. In the experiment of i.p. administration of selected neuropeptides, the level of ir-TRH in the stomach was significantly decreased after VIP injection, whereas it was significantly increased after beta-endorphin injection. The concentration of PGE2 was significantly decreased in the stomach after i.p. administration of TRH and VIP. However, it did not change after beta endorphin injection. These results indicate that some neuropeptides may participate in regulating the endogenous level of PGE2 and that these interrelations between neuropeptides and PGE2 may be important as ulcerogenic factors in stress ulcers induced by water-immersion in the rat. PMID- 1916150 TI - Role of mucosal blood flow in duodenal ulcer formation induced by dulcerozine. AB - To clarify the role of mucosal blood flow in the pathogenesis of ulcer formation, the authors investigated dulcerozine-induced duodenal ulcers in rats. Administration of dulcerozine, 500 mg/kg by intragastric route or 250 mg/kg given intraperitoneally, induced acute ulcers in the duodenum, but not the stomach, in all rats. Using the pyloric ligation method, it was determined that although dulcerozine significantly increased gastric acid secretion, no duodenal ulcers were observed in these animals. The administration of 1 ml of 0.1 N HCl every hour for 6 hours did not induce duodenal ulceration. The mucus glycoprotein content of the corpus, antrum and proximal duodenum did not differ following dulcerozine administration. Duodenal mucosal blood flow, which was measured by an electrolytically generated hydrogen gas clearance technique, decreased significantly following dulcerozine administration even in pylorus-ligated rats. In contrast, there was an increase in the gastric mucosal blood flow following administration of the drug. Therefore, not only an increase in gastric acid secretion but also a decrease in duodenal mucosal blood flow are suggested to be responsible for dulcerozine-induced duodenal ulceration. PMID- 1916151 TI - Mechanism of feminization in male patients with non-alcoholic liver cirrhosis: role of sex hormone-binding globulin. AB - We measured serum sex hormone-binding globulin (SHBG) using a radioimmunoassay developed by us, testosterone (T), estradiol (E2), free T and free E2 in 50 male patients with non-alcoholic liver cirrhosis (compensated: 30, decompensated; 20) and age-matched healthy male subjects, SHBG was significantly increased in patients with liver cirrhosis compared with healthy subjects. The high serum SHBG level in male compensated cirrhotic patients tended to decrease with progression to the decompensated state. Serum cholinesterase showed a positive correlation with SHBG in liver cirrhosis. Serum free T and the T/SHBG ratio decreased, while serum E2, free E2, and the E2/T and the free E2/free T ratios increased in liver cirrhosis, resulting in estrogen predominance and feminization of male patients. These changes were more marked in decompensated than compensated liver cirrhosis. An increased free E2/free T ratio was observed in patients with gynecomastia, palmar erythema or vascular spider. The T/SHBG ratio showed a positive correlation with serum free T, suggesting that it can be used as a free T index in liver cirrhosis. From these observations, it is suggested that serum SHBG plays an important role, by regulating the serum free T level in the occurrence of feminization in male patients with non-alcoholic liver cirrhosis. PMID- 1916152 TI - Genotyping of the aldehyde dehydrogenase 2 (ALDH2) gene using the polymerase chain reaction: evidence for single point mutation in the ALDH2 gene of ALDH2 deficiency. AB - About half of all Japanese lack the activity of aldehyde dehydrogenase 2 (ALDH2), and suffer a flush after alcohol intake due to the marked elevation of blood acetaldehyde concentration. The cause of ALDH2 deficiency is thought to be a single point mutation in codon 487 of the ALDH2 gene. However, this mutant ALDH2 gene has not yet been cloned and sequenced. We amplified and cloned the exon 12 of the ALDH2 gene using polymerase chain reaction (PCR), and revealed that normal GAA coding glutamic acid is replaced for AAA coding lysine in codon 487 of the mutant ALDH2 gene. Based on this finding, we performed the genotyping of the ALDH2 gene using PCR and allele-specific oligonucleotide probes. The genotypes of 13 subjects with ALDH2-active phenotype were all homozygous for the normal ALDH2 gene (ALDH2(1)), while in 9 subjects with ALDH2-deficient phenotype 2 subjects were homozygous for the mutant ALDH2 gene (ALDH2(2)) and the other 7 subjects were heterozygous for both genes, indicating that the mutant ALDH2 gene is dominant. In 20 normal control subjects, the prevalence of ALDH2(1)/ALDH2(1), ALDH2(1)/ALDH2(2) and ALDH2(2)/ALDH2(2) was 45%, 45% and 10% respectively. On the other hand, in 36 alcoholic liver disease patients, the prevalence of the genotypes was 83%, 17% and 0%. These results confirmed the previous observation that the incidence of ALDH2 deficiency is much lower in alcoholic liver disease patients than in the general population, and suggested that most of the ALDH2 deficient patients with alcoholic liver disease are heterozygous for the normal and mutant ALDH2 genes. PMID- 1916154 TI - Electron microscopic studies on duck hepatitis B virus particles in hepatocytes and sequential changes in various patterns of infection. AB - To investigate the critical factors involved in the elimination of the duck hepatitis B virus (DHBV) in acute infection, the sequential changes in the number of DHBV particles in hepatocytes were studied electron microscopically in ducks experimentally infected by DHBV. Twenty Japanese white Peking ducks were infected with DHBV on the day of hatching, and on the 7th day and 14th day after hatching. Inoculation of DHBV on the day of hatching, and on the 7th and 14th day after hatching resulted in persistent viremia, transient viremia and no viremia, respectively in ducks as tested by spot hybridization assay. The number of DHBV particles in the liver correlated well with the amount of serum DHBV-DNA, DHBV particles decreased in hepatocytes without any interaction of inflammatory cells over the observation period, and the number of particles was not associated with the degree of hepatic inflammation. From these results, the elimination of the virus was thought to be induced by a reduction of viral replication in the hepatocytes and not by destruction of their host cells. There must be an age dependent factor which strongly suppresses the viral replication. PMID- 1916153 TI - Significance of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in the pathogenesis of fulminant hepatitis: possible involvement of serine protease in TNF-mediated liver injury. AB - The effect of tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1) alpha, which are thought to be principal mediators inducing homeostatic abnormalities during endotoxemia, were investigated on cultured hepatocytes in an attempt to understand their role in the pathogenesis of fulminant hepatitis. Both TNF and IL 1 had no direct cytotoxicity on cultured adult rat hepatocytes as assessed by their effects on protein synthesis and also cytosolic enzyme activity released into the culture medium in the presence of 5 mM D-galactosamine (Ga1N). However, IL-1 caused a dose-dependent inhibition of DNA synthesis in cultured adult rat hepatocytes. Moreover, the serum from TNF-treated rats, prepared after intravenous administration of TNF (5 X 10(4) U per rat), caused a significant increase of enzyme release into culture medium in contrast to control rat serum. The cytotoxicity disappeared when the serum from TNF-treated rats was pretreated by heating at 56 degrees C for 30 min, and was decreased by the addition of the protease inhibitor, aprotinin. In vivo, gabexate mesilate, a serine-type protease inhibitor, prevented GalN/TNF-induced fulminant hepatitis, whereas MX-1, an anti complement agent, had no such effect. These results strongly suggest that IL-1 has a inhibitory effect on hepatocytes in terms of DNA synthesis and that TNF indirectly induces hepatocellular damage through the serine proteases which are possibly activated by the cytokine in vivo. PMID- 1916155 TI - Hepatic collagen synthesis in patients with alcoholic and nonalcoholic liver disease. AB - To examine the synthesis of hepatic collagen in patients with alcoholic and nonalcoholic liver disease, liver biopsy specimens were incubated in vitro with 14C-proline, and the radioactivity of the newly synthesized protein-bound 14C hydroxyproline was measured. Mean hepatic collagen synthesis was 0.82 +/- 0.19 pmole of 14C-hydroxyproline/g liver/2 h in control subjects without histological liver fibrosis. Hepatic collagen synthesis was increased in patients with alcoholic and nonalcoholic liver diseases, especially in those with alcoholic fibrosis, alcoholic cirrhosis and chronic active hepatitis. The raised collagen synthesis in alcoholic liver disease rapidly decreased after withdrawal of alcohol. When alcoholic liver disease were compared with nonalcoholic liver disease, there was no significant difference in hepatic collagen synthesis. PMID- 1916156 TI - Albumin mRNA expression in human liver diseases and its correlation to serum albumin concentration. AB - The expression of albumin mRNA in human liver samples was investigated in order to understand the molecular mechanism of albumin gene expression in various liver diseases. Albumin mRNA in acute hepatic failure and decompensated liver cirrhosis was reduced significantly compared to normal control liver (P less than 0.05). Serum albumin concentration is closely correlated with albumin mRNA content (r = 0.895, P less than 0.01). These data suggest that albumin concentration is mainly regulated at albumin mRNA level in the liver despite the presence of other regulatory mechanisms and that expression of albumin mRNA level is correlated with disease severity. But in several cases there was a discrepancy between albumin mRNA level and severity of liver disease, so further investigation of the regulatory factors of albumin gene expression should be performed. PMID- 1916157 TI - Clinicopathological studies on solid and cystic tumors of the pancreas. AB - Three cases of pancreatic tumor in two females (case 1, case 3) and one male (case 2) were reported. Macroscopically cases 1 and 3, which were surrounded by a thick fibrous capsule, developed toward the outside of the pancreas and the cut surface showed mainly cystic degenerative areas filled with necrotic and hemorrhagic materials. In contrast with these two cases, case 2 was buried in the pancreatic tissue and the cut surface showed cystic degenerative areas in its center with a thick fibrous capsule and tumor cell nests invading beyond the capsule to the parenchyma of the pancreas. Microscopically each tumor was identical. The solid areas on the periphery were composed of sheets of polygonal uniform cells subdivided by delicate fibrovascular stalks. Near the degenerative areas, tumor cells lay on a delicate fibrovascular core in one or two layers, with pseudopapillary patterns. Mitotic figures were very rare. All three cases demonstrated immunoreactivity for alpha-1-antitrypsin, but not for islet hormones, tumor markers nor neuron-specific enolase. Although electronmicroscopically, zymogen granules were detected in cases 2 and 3, and annulate lamellae in cases 1 and 3, ductal cell character features were not so developed. From the above, these tumors were diagnosed as solid and cystic tumors of the pancreas. Furthermore, it was suggested that they differentiated in the direction of acinar cells. PMID- 1916158 TI - Role of phospholipid in the formation of large aggregates and dissolution of insoluble calcium salts in mode bile solution. AB - The role of phospholipid in the formation of large aggregates and the dissolution of insoluble calcium salts in bile was studied in mode bile solutions of various lipid compositions. Calcium carbonate was added as an insoluble calcium salt. As the ratio of phospholipid concentration to bile acid increased, the rate of bile acid in the formation of large aggregates increased; total calcium concentration also increased but Ca2+ concentration did not change. Furthermore, a close relationship between the sum of the bile acid and phospholipid concentrations in the large aggregate fraction and the total calcium concentration in model bile solutions was observed. It could be concluded that phospholipid plays a role in dissolution of insoluble calcium salts by promoting the formation of large aggregates in bile. PMID- 1916159 TI - Monitoring the pressure of the sphincter of Oddi by percutaneous transhepatic choledochoscopy: new method for evaluating motor function. AB - The pressure of the sphincter of Oddi was measured in 40 patients using a thin microtransducer introduced via percutaneous transhepatic choledochoscopy. Choledochograms of the Vaterian bile duct were classified into four types: N (normal), I, II and III. Judging from the length of the Vaterian bile duct and the degree of fibrosis observed in the biopsy specimens, duodenal papillitis was found to be more severe in Type III than in Type II. Nevertheless the systolic pressure was significantly lower in Type III. We considered that when duodenal papillitis is considerably advanced, the force of contraction of the sphincter is reduced. In addition, based on choledochoscopic observations, as duodenal papillitis increased in severity, the incidence of an irregular shape at the end of the common bile duct during diastole increased. The indications for endoscopic sphincterotomy were determined based on the pressure of the sphincter of Oddi in patients with normal duodenal papilla. In the 26 patients in whom the procedure was not indicated, no gallstones developed. In the 3 patients in whom the procedure was indicated and performed, gallstones have not developed. However, 3 of the 6 patients in whom the procedure was indicated but not performed developed gallstones. This method is useful in evaluating the motor function of the sphincter of Oddi under relatively physiological conditions. PMID- 1916161 TI - A case report of juvenile polyposis with adenomatous change and a review of 34 cases reported in Japan. AB - It has recently come to be thought that cases of juvenile polyposis have a natural tendency to develop adenoma and/or carcinoma. Here we present a case of juvenile polyposis coli with adenomatous change in a 21-year-old male, with a review of 34 cases of juvenile polyposis in the Japanese literature, and discuss the pathogenetic development of the polyps and their malignant potential. In this case, focal or entire adenomatous areas were found in large part of the polyps in the resected sigmoid colon and rectum, though these findings had not been recognized in 23 polypectomy specimens from the rectum 10 months prior to the operation. It was suggested that adenomatous change developed quickly in a very short time. PMID- 1916162 TI - Water immersion stress induces heat shock protein in mouse gastric mucosa. PMID- 1916160 TI - A case of small bowel carcinoma in Crohn's disease. AB - A 46-year-old man had symptoms of ileus four years and five months after being diagnosed as Crohn's disease. Upon small bowel radiography, a short, spindle shaped stenosis on the distal site of the ileum was found. In the resected specimen, there was a constricted area with wall hypertrophy, and the mucosal surface of this region was rough and granular. At the site of this region, well differentiated adenocarcinoma was noted, which infiltrated the serosa in the form of mucous adenocarcinoma. Transmural disproportional inflammation and non caseating granuloma were also around there. The X-ray findings in this case are considered to be useful for diagnosis of carcinoma during the long term observation period for Crohn's disease. PMID- 1916163 TI - Ethanol elevates intracellular calcium in rabbit parietal cells. PMID- 1916164 TI - Factors affecting human bile pH. PMID- 1916165 TI - Effect of local instillation of alcohol on sphincter of Oddi motor activity: combined ERCP and manometry study. AB - The effect of local instillation of alcohol on sphincter of Oddi motor activity was determined by endoscopic manometry. Sphincter of Oddi pressures and motor function were compared in eight cholecystectomized subjects with normal sphincter of Oddi motor function and in four patients with chronic alcoholic pancreatitis. The effect of local instillation of 3 ml of 40% alcohol was compared with water instillation. In cholecystectomized subjects, alcohol produced a significant increase of basal sphincter of Oddi pressure from 21.0 +/- 2.8 mm Hg to 95.8 +/- 83 mm Hg (p less than 0.01) without significant changes in the amplitude, duration, and frequency of phasic contractions. In patients with alcoholic chronic pancreatitis, alcohol instillation resulted in a significant increase of basal sphincter of Oddi pressure from 32.5 +/- 4.8 mm Hg to 225.1 +/- 105 mm Hg without changes in amplitude, duration, and frequency of phasic contractions. Two patients with chronic alcoholic pancreatitis had a tonic contraction of the sphincter of Oddi with transitory and mild epigastric pain. Local instillation of alcohol increases sphincter of Oddi motor activity which may play a role in the pathogenesis of alcoholic pancreatitis. PMID- 1916166 TI - Per-rectal pulsed irrigation versus per-oral colonic lavage for colonoscopy preparation: a randomized, controlled trial. AB - The aim of this study was to compare the efficacy and patient tolerance of a new pulsed irrigation system to colonic lavage for colonoscopic preparation. Thirty four prospective patients scheduled for routine colonoscopy were randomized to one of two preparations: a per-rectal pulsed irrigation device (18 patients) versus per-oral colonic lavage (15 patients). Colonoscopic preparation was assessed on a 0 to 4 plus scale by region and overall. This was done live and by video tape by two independent endoscopists who were blinded to the patient's preparation. There was no significant difference with respect to cleanliness of the colon with pulsed irrigation patients having an average overall preparation score of 3.00 +/- 0.19 (SEM) versus colonic lavage patients with a score of 3.14 +/- 0.19. There was also no statistically significant difference between the two groups with respect to demographics, time to reach the cecum, time for entire procedure, volume of aspiration or wash, or sedation given. We conclude that the new pulsed irrigation device provides an alternative to the standard per-oral lavage solution for colonoscopic preparation. PMID- 1916167 TI - Evaluation of submucosal upper gastrointestinal tract lesions by endoscopic ultrasound. AB - The proper diagnosis of submucosal upper gastrointestinal tract mass lesions by endoscopy or barium study is difficult. Differentiation between submucosal tumors, vascular structures, and extrinsic organs is often impossible. We performed endoscopic ultrasound examination of 91 patients with upper gastrointestinal submucosal mass lesions. Endoscopic ultrasound was accurate in determining the site of origin in 48 of 50 cases where pathology or angiography comparison was available. Leiomyoma, lipoma, varices, and carcinoma had characteristic ultrasonographic findings. Endoscopic ultrasound is a useful procedure in the evaluation of upper gastrointestinal submucosal mass lesions. PMID- 1916168 TI - Reproducible demonstration of blood flow at duodenal ulcer margins by endoscopic reflectance spectrophotometry. AB - Changes in gastrointestinal mucosal blood flow were evaluated by index of oxygen saturation (ISO2) and index of hemoglobin concentration (IHB) measured with a reflectance spectrophotometer. This report examined the reproducibility of endoscopic measurements of ISO2 and IHB. Study 1: The everted stomachs of three anesthetized rats provided hands-on instruction (one teacher and three learners). Six sets of readings were obtained endoscopically (the mean calculated to give the measurement) at each level of gastric mucosal perfusion when gastric blood flow was varied by withdrawing blood from the carotid artery. Study 2: Fourteen duodenal ulcer patients with ulcer bleeding were transfused and stabilized. Two endoscopists (one teacher and one learner) took turns to obtain endoscopic ISO2 and IHB measurements at the margin of the ulcer and at the adjacent normal appearing mucosa. delta ISO2 was calculated as the ulcer margin value minus adjacent mucosa value. In study 1, the correlation coefficients between the ISO2 measurements of the experienced and those of the other three observers were 0.99, 0.97, and 0.97, respectively. In study 2, the correlation coefficients between the ISO2 measurements obtained at the ulcer margin and at the adjacent normal mucosa, and delta ISO2 obtained by the experienced observer and one of the three learners were 0.94, 0.97, and 0.94, respectively. Relative to the adjacent area, 79% of the duodenal ulcers studied had increased (+delta ISO2), and 21% had decreased blood flow (-delta ISO2) at the ulcer margins. IHB measurements were less reproducible, particularly at the ulcer margin. The measurements of ISO2 and delta ISO2 were reproducible in the everted rat stomach and in duodenal ulcer patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916169 TI - Outcome of injection sclerotherapy using absolute alcohol in patients with cirrhosis, non-cirrhotic portal fibrosis, and extrahepatic portal venous obstruction. AB - In order to assess the comparative efficacy and safety of endoscopic injection sclerotherapy in patients with portal hypertension of different etiology, i.e., cirrhosis, non-cirrhotic portal fibrosis, and extrahepatic portal venous obstruction, 87 patients with variceal bleeding were initiated on sclerotherapy using absolute alcohol. There was no significant difference in the success rate of sclerotherapy as well as in the number of sessions and volume of alcohol required for variceal obliteration between the three groups. Major complications included esophageal ulcers (30.0%), symptomatic strictures (18.6%), and interval re-bleed (17.1%) with similar complication rates for the three groups (p greater than 0.05). There was no difference between patients with Child's class A cirrhosis compared with classes B and C together with respect to efficacy and complications of sclerotherapy. Fifty patients (25 cirrhosis, 11 non-cirrhotic portal fibrosis, and 14 extrahepatic portal venous obstruction) with complete variceal obliteration were followed up for a mean period of 16.5 months. Sixteen patients (32%) had variceal recurrence, but bleeding due to recurrent varices occurred in only one case. There was no difference among the three groups for overall variceal recurrence, although recurrence tended to be somewhat later in extrahepatic portal venous obstruction (9.4 +/- 4.0 months) compared with that in cirrhosis (5.1 +/- 3.6 months) and non-cirrhotic portal fibrosis (4.8 +/- 2.6 months). PMID- 1916170 TI - Endoscopic transesophageal fine needle aspiration of mediastinal masses. PMID- 1916171 TI - ERCP findings in hepatic alveolar echinococcosis. PMID- 1916172 TI - Fasciola hepatica pancreatitis: endoscopic extraction of live parasites. PMID- 1916173 TI - Endoscopic diagnosis of hookworm infection. PMID- 1916174 TI - Multiple left-sided colon ulcers due to typhoid fever. PMID- 1916175 TI - Metastatic implantation of laryngeal carcinoma at a PEG exit site. PMID- 1916177 TI - Repeated hydrostatic balloon dilation in obstructive gastroduodenal Crohn's disease. PMID- 1916176 TI - Gastric chloroma associated with upper gastrointestinal tract bleeding. PMID- 1916178 TI - Submucosal gastric hemorrhage following extracorporeal shock wave lithotripsy of bile duct stones. PMID- 1916179 TI - Endoscopic sphincter of Oddi manometry: a clinical practice and research tool. PMID- 1916180 TI - Bipolar electrocoagulation treatment for hemorrhagic radiation injury of the lower digestive tract. PMID- 1916181 TI - Direct percutaneous endoscopic jejunostomy. PMID- 1916182 TI - Colonoscopy in patients with large inguinal hernias. PMID- 1916183 TI - Needle knife sphincterotomy: a necessary tool. PMID- 1916184 TI - Duodenal migration and retrieval of metallic biliary stent. PMID- 1916185 TI - Pseudo-migration of a biliary stent. PMID- 1916186 TI - Absolute alcohol as an esophageal variceal sclerosant. PMID- 1916187 TI - Is fluoroscopy mandatory for achalasia dilation? PMID- 1916188 TI - Tuberculosis in a colonic juvenile retention polyp. PMID- 1916189 TI - Colonoscopic disimpaction of the appendiceal orifice. PMID- 1916191 TI - Utilization of a needle biopsy for histological diagnosis of a submucosal mass. PMID- 1916190 TI - Pseudomembranous colitis associated with endocarditis prophylaxis for endoscopy. PMID- 1916192 TI - Pull-enteroscopy. PMID- 1916193 TI - Calcium channel blockers and gingival hyperplasia. PMID- 1916194 TI - Erythematous gingiva with spontaneous bleeding. PMID- 1916195 TI - Midline gingival mass. PMID- 1916196 TI - Matrix band adaptation for "wraparound" Class II amalgams. PMID- 1916197 TI - A safe and convenient means of recapping needles. PMID- 1916198 TI - Ankyloglossia: a review of the literature. PMID- 1916199 TI - Stability of epinephrine in local anesthetic cartridges. PMID- 1916200 TI - The report of the panel to develop radiographic selection criteria for dental patients. PMID- 1916201 TI - Dentistry as portrayed in literature and popular entertainment. PMID- 1916203 TI - An interdisciplinary approach to treating psychogenic pain in the dental implant patient. PMID- 1916202 TI - Undoing iatrogenic odontophobia. PMID- 1916204 TI - An unusual case of an erupting microsupernumerary tooth. PMID- 1916205 TI - Phylogenetic aspects of pancreastatin- and chromogranin-like immunoreactive cells in the gastro-entero-pancreatic neuroendocrine system of vertebrates. AB - Using a battery of region-specific antisera raised against different amino acid sequences of pancreastatin (Pst) (Pst-1-6, Pst-1-17, Pst-14-49, Pst-33-49) as well as two antisera raised against chromogranin (Cg) A and CgA/B and the biotin avidin technique, the phylogenetic distribution of Pst-immunoreactive (-IR) and Cg-IR cells was studied in the gastroentero-pancreatic (GEP) neuroendocrine system. The investigation was carried out with representatives of all vertebrate classes as well as with the protochordates Branchiostoma lanceolatum and Ciona intestinalis. The study revealed the presence of Pst-IR and Cg-IR cells in the gastro-intestinal mucosal epithelium as well as in the islet parenchyma of all vertebrates studied with the only exception found in rat. In the rat GEP system unequivocal immunoreactions were obtained only by the use of antiserum CgA/B. In the gastro-intestinal tract of the deuterostomian invertebrates no Pst-IR or Cg IR cells could be observed with any of our antisera. Whether this might indicate that Pst-like or Cg-like peptides are characteristic for vertebrates or, more likely, whether similar proteins/peptides might be present in the alimentary tract of protochordates which do not react with the antisera at hand, remains to be clarified. Thouh pronounced interspecies and some intraspecies differences were found, several general conclusions can be drawn. In all vertebrate species, the Pst-IR and Cg-IR cells observed in the mucosal epithelium of the gastro intestinal tract showed an endocrine structure and were of the so-called open type. The Pst and the Cg antisera which gave immunoreactions with parenchymal cells in the islets of Langerhans also reacted with cells in the epithelium of the pancreatic ducts. Comparative analysis of the reaction properties of the region-specific antisera used indicated that the Pst-like material in the islet cells of the cartilaginous fish species studied seems to be "mammalian-like," whereas it appears to be different in the other (phylogenetically younger) submammalian vertebrates. In addition, the Pst-like peptides in the gastro intestinal mucosal epithelium and in those in the islets seem to differ in most submammalians. Finally, in the pyloric-duodenal junction of the quail (Coturnix c. japonica) the presence of a so far unknown peptide of the Cg family is presumed. In general, our results seem to indicate that the phylogeny of Pst-like and Cg-like peptides is not as "straight" as those which have been demonstrated for several other neurohormonal peptides.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1916206 TI - Kinetic analyses of peptidylglycine alpha-amidating monooxygenase from pancreatic islets. AB - Peptidylglycine alpha-amidating monooxygenase (PAM) plays an important role in the post-translational processing of bioactive neuropeptides by participating in C-terminal amidation. We have examined PAM activity in the pancreatic islets of the anglerfish (AF), Lophius americanus. It was previously demonstrated that the cofactor requirements and pH optimum for the fish PAM are essentially identical to PAM obtained from other tissues and species. The present study was performed to examine the enzymatic characteristics of the fish islet PAM in more detail. One of the questions addressed was the suitability of the AF islet neuropeptide Y like peptide, aPY-Gly, as a substrate for the islet PAM. Partially purified PAM from AF islet secretory granules was incubated with [125I] aPY-Gly and the resulting products were analyzed by HPLC. The islet PAM readily mediated the formation of aPY-amide from aPY-Gly. PAM purified from bovine adrenal chromaffin granules also catalyzed the amidation of [125I] aPY-Gly. The kinetic parameters of the islet PAM were examined using trinitrophenylated-D-Tyr-Val-Gly (TNP-D-YVG) and 4-nitrohippuric acid (4-NHA). The Km of the islet PAM was 25 +/- 5 microM for TNP-D-YVG and 3.4 +/- 1 mM for 4-NHA. The competitive inhibitor of mammalian PAM activity, 4-methoxybenzoxyacetic acid, proved to be a potent inhibitor of the islet PAM as well, with an apparent KI of 0.06 mM. These results demonstrate that the AF islet PAM exhibits substrate compatibility, kinetic parameters, and inhibitor susceptibility quite similar to the characteristics of PAM from other tissues and species. PMID- 1916207 TI - Histology, ultrastructure, and in vitro steroidogenesis of the testes of two male phenotypes of the protogynous fish, Thalassoma duperrey (Labridae). AB - Species with multiple male reproductive phenotypes may serve as model systems to study the relationship between form and function in reproduction. Large and small males of the protogynous wrasse, Thalassoma duperrey differ in reproductive behavior, gonad morphology, and gonadal steroid production. Initial-phase (IP) males are small males that spawn in groups. They have large testes with high sperm production. Terminal-phase (TP) males are large, defend temporary spawning territories, and spawn individually with females. TP males are derived from either IP males or from sex-changed females. Regardless of origin, TP males have much smaller testes than do IP males, but steroid-producing Leydig cells in the gonads of TP males appear more numerous and better developed. Testes of TP males produce more testosterone (T) and especially 11-ketotestosterone (11-KT) in vitro than do testes of IP males, and the production is more responsive to salmon gonadotropin. 11-KT was the major metabolite produced by incubating the gonads of TP males with 14C-labeled steroid precursors. In vitro 11-KT production was correlated with plasma levels of 11-KT in TP males and these levels were significantly higher than those of IP males. The in vitro conversion of 17 alpha hydroxyprogesterone to 17 alpha, 20 beta-progestogen (17 alpha, 20 beta-P) for both types of males was similar, and was highest in winter when spawning occurred every day. Basal production of 17 alpha, 20 beta-P was similar in IP and TP male testes, and was enhanced by gonadotropin. The enzyme 20 beta-hydroxysteroid dehydrogenase, responsible for the conversion of 17 alpha-hydroxyprogesterone to 17 alpha, 20 beta-P resided in the sperm. These results indicate a function of 17 alpha, 20 beta-P in male reproductive function, probably spermiation, and a relationship of Leydig cell development and high levels of 11-KT production to the terminal male phenotype, perhaps reproductive or aggressive behavior, rather than to male gametogenesis per se. PMID- 1916208 TI - The complete amino acid sequence of prolactin from the bullfrog, Rana catesbeiana. AB - The complete amino acid sequence of prolactin (PRL) from an amphibian species, the bullfrog (Rana catesbeiana), has been determined and conserved residues and domains were analyzed by sequence comparison of PRLs from 15 species of five major vertebrate classes. The bullfrog PRL consists of 197 amino acid residues with three disulfide linkages formed between residues 4-11, 58-172, and 189-197. The bullfrog PRL shows the highest identity with sea turtle PRL (75%); lower identities with chicken PRL (72%), pig, horse, and fin whale PRLs (68%), human, cattle, sheep, and elephant PRLs (60-58%), and rat and mouse PRLs (50%); and significantly lower identity with teleost PRLs (about 30%). It is apparent that all tetrapod PRLs characterized so far contain three disulfide bonds in homologous positions and differ from teleost PRLs which lack the N-terminal disulfide loop. The tetrapod and teleost PRLs share 34 common residues and these conserved residues are clustered in six domains (PD1 to PD6), suggesting that these common residues, or at least part of them, are responsible for the activities common to all PRLs. On the other hand, PD5 is conserved significantly within tetrapod PRLs, but to a lesser extent in teleost PRLs, suggesting that the PD5 contributes to the activities specific to tetrapod PRLs. PMID- 1916209 TI - Isolation and primary structure of glucagon from the endocrine pancreas of Thunnus obesus. AB - Glucagon has been isolated from the endocrine pancreas of a tunid, Thunnus obesus. The primary structure of the glucagon molecule was established as H S E G T F S N D Y S K Y L E T R R A Q D F V Q W L K N S. The sequence is identical to those of sculpin and flounder glucagon and glucagon II from anglerfish. It also shows high homology to the mammalian hormone (76%). The mass determined by fast atom bombardment (3508) was consistent with the proposed structure. Immunological properties of the tuna glucagon were analyzed by radioimmunoassay, showing a high degree of cross-reactivity with the 30K antibody. PMID- 1916210 TI - Cells in the intestinal system of holothurians (Echinodermata) express cholecystokinin-like immunoreactivity. AB - The presence of cholecystokinin (CCK), originally isolated from porcine small intestine, has been reported in a diversity of invertebrates ranging, from cnidarians to protochordates, but so far, not in echinoderms. We have used immunohistochemical techniques to demonstrate the presence of cells expressing CCK-like immunoreactivity in the intestine of three species of sea cucumber: Holothuria mexicana, H. glaberrima, and Stichopus badionotus. The immunoreactivity was observed within the cytoplasm of these cells, in what appeared to be granular or vesicle-like structures. The cell bodies were present in the outer connective tissue layer of the intestine and had a neuronal appearance, sending an axon-like structure into the circular muscle and internal connective tissue. A plexus of fibers expressing CCK-like immunoreactivity was found overlying the muscle layer. Contractility of H. mexicana intestinal strips was studied under partially isometric conditions. CCK and related peptides induced relaxation of the basal muscle tension, and of tension induced by ACh application, suggesting a role for this agent in the intestinal physiology of holothurians. PMID- 1916211 TI - Steroidogenic cell subpopulations obtained from the theca of preovulatory follicles in the ovary of the domestic fowl. AB - The purpose of the present study is to provide further evidence in support of the theory which suggests that two cells are involved in the secretion of estrogens and androgens in the theca of the preovulatory ovarian follicles in the domestic fowl. The third (F3), the fourth (F4), and the fifth (F5), in order of decreasing size follicles, were obtained from white Leghorn hens. Theca cells were dispersed by trypsin treatment, and isolated cells were centrifuged in a continuous Percoll gradient (0-100%). Testosterone and 17 beta-estradiol secretion from cell samples in each density gradient fraction were radioimmunologically assayed. The highest secretion of 17 beta-estradiol was registered in cells isolated in density fractions ranging from 1.059 to 1.070 g/ml, while the maximal testosterone production was found in fractions from 1.037 to 1.048 g/ml. The different results were obtained from the three types of follicles studied (F3-F5). Morphological study of the F4 follicle showed typical steroidogenic cells with abundant lipid droplets in the cytoplasm in the theca interna, whereas clusters of poorly differentiated epithelial cells were visualized between fibroblast layers of the theca externa. The secretion of aromatizable androgens by the typical steroidogenic cells of the theca interna and estrogen production in the epithelial cells of the theca externa are postulated. PMID- 1916212 TI - In vitro effects of arginine vasotocin on testosterone production by testes of rainbow trout (Oncorhynchus mykiss). AB - The objective of this study was to investigate the effect of arginine vasotocin (AVT) on testosterone (T2) production by the rainbow trout testis in culture. AVT increased T2 production in a dose-dependent manner in immature testes. The maximum response (10 nM AVT) increased T2 production 6-fold over basal (3-6 pg/mg tissue protein). Mature testes did not respond to AVT. Salmon gonadotropin (2.5 nM sGtH, SGA-GtH) stimulated T2 production by both juvenile (5-fold) and mature (11-fold) testes. When AVT (100 nM) was added in addition to salmon gonadotropin (sGtH; from 0.1 to 100 nM), AVT had a stimulatory effect at the submaximal doses of sGtH, but T2 production did not exceed the maximum level obtained with sGtH (100 nM) alone. Isotocin also increased T2 production although to a lesser degree than AVT. The maximum response at 10 nM increased T2 production 4-fold over basal. beta-Endorphin had no effect on T2 production. PMID- 1916213 TI - Levels of 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one, 3 beta,17 alpha,20 alpha trihydroxy-5 beta-pregnane, and other sex steroids, in blood plasma of male dab, Limanda limanda (marine flatfish) injected with human chorionic gonadotrophin. AB - In a previous study, plasma sex steroid levels were measured in female dab (Limanda limanda) induced to ovulate by injections of human chorionic gonadotrophin (HCG). In the present study, a similar experiment was carried out on male dabs. In common with female dabs, 17 alpha,20 alpha-dihydroxy-4-pregnen-3 one and 3 beta,17 alpha,20 alpha-trihydroxy-5 beta-pregnane showed the greatest response. Their plasma levels increased, respectively, from 6 +/- 1.6 and 13 +/- 6.2 ng/ml to ca. 62 ng/ml within 36 hr and then decreased. Levels of both steroids remained low in fish injected with saline. There was no statistically significant effect of HCG on plasma testosterone or 11-ketotestosterone concentrations. Initial levels of both hormones were between 10 and 20 ng/ml, and decreased simultaneously in both HCG- and saline-injected fish. Levels of 17 alpha-hydroxy-4-pregnen-3,20-dione, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, 11-deoxycortisol, and 17 alpha,20 beta, 21-trihydroxy-4-pregnen-3-one were mostly below the detection limits of the assays (0.4 ng/ml). There was no statistically significant effect of HCG on either the total volume of milt collected or the proportion occupied by spermatozoa. PMID- 1916214 TI - Immunoaffinity purification and partial characterization of sea bass (Dicentrarchus labrax) growth hormone. AB - Growth hormone (GH) was isolated from sea bass (Dicentrarchus labrax) pituitary extract by a simple one-step procedure involving immunoaffinity chromatography. A monoclonal antibody raised against chicken GH and found to immunostain very specifically the GH cells in the pituitary of the sea bass was coupled to CNBr activated Sepharose 4B. Sea bass pituitary extracts were run on the affinity column, and the eluted material was analyzed on reversed-phase HPLC and found to consist of one single peak. The yield of purified hormone was 2.4 mg/g pituitary. Two monomeric forms (MW = 20,000 and 22,000 Da) of sea bass GH were identified by gel electrophoresis. Gel electrofocusing revealed apparent isoelectric points of 6.15, 6.50, and 6.95. Amino acid composition is consistent with other vertebrate GHs. The immunological relatedness was tested by immunoblotting using antisera raised against GH of different species. Polyclonal antisera raised against the isolated hormone exhibited a specific labeling of the GH cells in sea bass pituitary sections as well as of the immunoblotted purified GH. PMID- 1916215 TI - Comparison of in vivo biological activities of luteinizing hormone releasing hormone (LHRH) analogues in 60-day-old cockerels. AB - The in vivo biological activities of various luteinizing hormone releasing hormone (LHRH) analogues in immature 60-day-old cockerels were compared, based on their capacity to increase circulating luteinizing hormone (LH) concentrations. Intravenous injections of 50, 100, or 500 ng of [Gln8]LHRH (cGnRH-I) and [His5,Trp7,Tyr8]LHRH(cGnRH-II) induced significant increases in the plasma LH level. The maximum response was always observed 2 min after the injection. Mammalian LHRH(mGnRH) significantly increased plasma LH, but only at the 500 ng dosage level. [Ile8]LHRH, [D-Ala6]LHRH, [Ala4]LHRH, [Leu8]LHRH, and [Phe5]LHRH increased plasma LH at 50-500 ng. [Ile7]LHRH, [Phe3]LHRH, and [Phe2]LHRH did not significantly increase plasma LH. Relative in vivo biological activities, calculated from dose (30-100 ng)-response curves of mGnRH-I, cGnRH-I, cGnRH-II, [Ile8]LHRH, [D-Ala6]LHRH, [Ala4]LHRH, [Leu8]LHRH, [Ile5]LHRH, [Ile7]LHRH, [Phe3]LHRH, and [Phe2]LHRH were 1.00, 1.40, 1.81, 1.50, 4.59, 1.90, 1.28, 1.56, 0.57, 0.67, and 0.57, respectively. These results demonstrate that avian LHRHs have higher biological activities than mammalian LHRH in the chicken. Furthermore, cGnRH-II is more potent than cGnRH-I, and [D-Ala6]LHRH has a very high activity while [Ile7]LHRH and [Phe2]LHRH have very low activities. PMID- 1916216 TI - Progestins and cortisol delay while estradiol-17 beta induces early parturition in the guppy, Poecilia reticulata. AB - Fertilization and gestation are intrafollicular in the guppy (Poecilia reticulata), and ovulation occurs at the end of gestation prior to parturition. In this study, the effects in vivo of the ovarian steroids, progesterone, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-P), cortisol and estradiol-17 beta, the antiprogestin RU 486, and aromatase inhibitor, 4 hydroxyandrost-4-ene-3,17-dione (4-HAD), on gestation and parturition were studied in the guppy. Progesterone (0.05 and 0.10 micrograms/ml of water), 17 alpha,20 beta-P (0.01 micrograms/ml and greater), cortisol (0.10 micrograms/ml) and 4-HAD (0.10 micrograms/ml) all prolonged gestation presumably by inhibiting ovulation. 17 alpha,20 beta-P was most effective in inhibiting ovulation and parturition for up to 36 days postpartum. This inhibition was reversed when fish were transferred to steroid-free water. Besides extending gestation, 17 alpha,20 beta-P and 4-HAD also inhibited development of vitellogenic oocytes. Estradiol-17 beta (0.05 and 0.10 micrograms/ml) and RU 486 (10 micrograms/g body weight) both induced premature parturition presumably by accelerating onset of ovulation. These results, together with our previous observations on the steroid profile in the guppy, strongly suggest roles for estradiol-17 beta and cortisol in regulating ovulation and parturition. PMID- 1916217 TI - Phenotypic inhibition of the renin-angiotensin system, emergence of the Ren-2 gene, and adaptive radiation of mice. AB - The renin-angiotensin system in sub-genus Mus displays unique features including duplication of the renin gene in most strains, strong expression of the second gene in submandibular gland of males, and inhibited responses to injected renin. Our findings indicate that this inhibition results from a paucity of renin substrate and is consistent with first-order kinetics. We find substrate paucity to be a feature of both sexes and all sub-species and strains of Mus irrespective of gene duplication. Attempts to increase the level of substrate in blood by intravenous injection caused marked increases in blood pressure in Mus, suggesting that substrate paucity was a phenotypic prerequisite for successful emergence of enhanced renin expression in salivary gland. We propose that these phenomena are linked to salivary "lethal factor", possibly transferred by biting, in an evolutionary sequence that has provided a major selective advantage for Mus and influenced the ecology and evolution of rodents. PMID- 1916218 TI - Progesterone downregulates progesterone receptor, but not estrogen receptor, in the estrogen-primed oviduct of a turtle (Trachemys scripta). AB - Progesterone downregulates nuclear progesterone receptor (Rp) and estrogen receptor (Re) in the estrogen-primed mammalian uterus and chick oviduct. We sought to determine if this downregulation mechanism is operative in the turtle oviduct. Female turtles were primed for 4 days with 17-beta-estradiol, after which progesterone (5 mg) was administered by injection every 24 h. Re and Rp levels in progesterone-treated and control turtle oviducts were measured by [3H]steroid-binding assays (pyridoxal 5' phosphate method) at 12, 24, 48 and 72 hr after initial progesterone treatment. Serum progesterone levels of progesterone-treated turtles increased only slightly from 0 hr (0.3 ng/ml) to 12 hr (0.6 ng/ml) after progesterone administration, increased considerably by 24 hr (5.3 ng/ml), and remained elevated (6-8 ng/ml) through 72 hr. Cytosol and nuclear Rp levels of estrogen-primed turtle oviducts showed distinct seasonal variation, with Rp levels higher in spring and summer months than in winter months. There was no seasonal variation in Re levels. Both cytosol and nuclear Rp responded to progesterone treatment. Cytosol Rp levels of progesterone-treated oviducts were significantly reduced below control levels by 12 hr after progesterone administration and remained low through 72 hr. Nuclear Rp levels of progesterone treated oviducts showed no change at 12 hr, increased at 24 hr and then dropped at 48 and 72 hr. However, progesterone did not downregulate Re in the turtle oviduct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916219 TI - Effects of some potassium channel blockers on the ionic currents in myelinated nerve. AB - The effects of some potassium channel blockers on the ionic currents and on the so-called K(+)-depolarization in intact myelinated nerve fibres were studied. 4 AP, and in particular, Flaxedil, proved to be selective K(+)-current blockers. However, TEA, a crown ether (DCH18C6), a longchained triethylammonium compound (C10-TriEA), capsaicin, and the extract from the medicinal herb Ruta graveolens proved not to be selective K(+)-current blockers; they all block Na(+)-currents as well, although to a lesser extent. The sodium inactivation curve did not change under TEA and Flaxedil but was shifted on the potential axis in negative direction by DCH18C6, 4-AP, capsaicin and the Ruta extract whereas C10-TriEA caused a shift of both sodium inactivation and activation parameters in positive direction. Regarding to the kinetics of the persisting K(+)-current fraction, two different kinds of blockade were found: 1. Unchanged K(+)-kinetic which is typical for the effects of TEA, 4-AP, Flaxedil, and C10-TriEA. 2. Clearly changed K(+)-kinetic, characterized by K(+)-transients; which is typical for the effects of capsaicin and in particular, for those of DCH18C6 and of the Ruta extract. The possibly different modes of action of both groups of blockers are discussed in terms of current models for the action of potassium channel blockers. PMID- 1916220 TI - Conformational changes of contractile proteins accompanying modulation of skeletal muscle contraction. Polarized microfluorometry investigations. AB - Results of studies on the modulation of skeletal muscle contraction by phosphorylation of myosin regulatory light chains and by exchange of magnesium for calcium in myosin heads were reviewed. The polarized fluorescence method was used in these studies, and conformational changes of contractile proteins accompanying modulation of skeletal muscle contraction were investigated. It was found that both the exchange of bound magnesium for calcium on myosin heads and the phosphorylation of myosin regulatory light chains control the ability of myosin heads to induce, upon binding to actin, conformational changes of thin filament leading to decrease or increase of its flexibility. The changes in actin filament flexibility may be caused by alteration of both the inter- and the intramonomer structural organization. PMID- 1916221 TI - Na(+)-Ca2+ exchange in the rat brain during ontogeny. AB - A rise of Na(+)-Ca2+ exchange during ontogenic development was found in the rat brain which parallels brain maturation. Nerve endings are the main structure which contributes to the rise of the exchange activity. PMID- 1916222 TI - Effects of substituted aryloxyaminopropanols on photosynthesis and photosynthesizing organisms. AB - The inhibitory activity of 22 substituted aryloxyaminopropanols having beta-lytic and local anaesthetic properties was studied from the view-point of their influences on photosynthesis in plant chloroplasts as well as growth and synthesis of chlorophyll in algae and wheat plants. The inhibitory activity increased significantly with the increasing length of alkyl-substituents of the aryloxyaminopropanol molecule. Less pronounced dependences were found with respect to the position of the substituent chain on benzene ring. The inhibitory activity was found to correlate well with the lipophilicity of the compounds studied. PMID- 1916223 TI - Biosynthesis of trichothecene mycotoxins: cell-free epoxidation of a trichodiene derivative. AB - A cell-free enzyme system from cultures of Fusarium culmorum catalyses the 12,13 epoxidation of semi-synthetic 9 beta,10 beta-epoxytrichodiene to 9 beta,10 beta;12,13-diepoxytrichodiene. This enzyme activity may be involved in the biosynthesis of trichothecene mycotoxins and since the 12,13-epoxide is known to be essential for toxicity, the enzyme activity probably confers the toxic properties associated with this group of mycotoxins. The epoxidase requires NADPH and molecular oxygen, is inhibited by carbon monoxide, and thus appears to be a cytochrome P-450-dependent mono-oxygenase. Whole cell cultures of the fungus carry out the same biotransformation, and in addition hydroxylate the diepoxide product at position 3, yielding 3 alpha-hydroxy-9 beta,10 beta;12,13 diepoxytrichodiene. PMID- 1916224 TI - Protein and other compositional differences of the extracellular material from slimy and non-slimy colonies of non-mucoid Pseudomonas aeruginosa. AB - The composition of extracellular material produced by non-mucoid strains of Pseudomonas aeruginosa differed when grown on surfaces that either did or did not induce the formation of slime under conditions where the medium was identical. The nature of the changes in protein composition indicated that protein expression differed in the course of growth on the two surfaces, and hence that there were physiological consequences associated with growth under conditions which do or do not lead to slime formation. The compositional differences also included elevated levels in extracellular material from the slimy colonies of two virulence factors, protease and rhamnolipids. PMID- 1916225 TI - Amplification of the secretory IgA response to Toxoplasma gondii using cholera toxin. AB - Our study demonstrates that cholera toxin (CT) markedly enhances the intestinal anti-T. gondii antibody response following oral immunisation of mice with a T. gondii sonicate (TSo) and CT. The antibodies induced were mostly IgA and secretory IgA but a small quantity of IgG was also produced. In contrast, no intestinal anti-T. gondii IgM antibodies were detected. Anti-CT IgA antibodies were also present in intestinal secretions but in much lower quantities than the T. gondii-specific IgA. No anti-CT IgG nor IgM antibodies were detected. Western blot analysis showed that CT induced not only an increase of the intensity of the intestinal IgA antibody response to the 30-kDa band but also induced intestinal IgA antibodies against other major T. gondii proteins (p22, and the 28-kDa antigen) as recognised by specific monoclonal antibodies. The amplification of the anti-T. gondii secretory IgA response by means of an appropriate adjuvant may be one major step leading towards an orally induced immune protection against toxoplasmosis. PMID- 1916226 TI - Enhanced intraspecific protoplast fusion in yeast. AB - Intraspecific hybrid production from the polyethylene glycol induced fusion of yeast protoplasts was greatly increased when calcium propionate was included as the source of the requisite Ca2+. The use of calcium propionate, as opposed to the more commonly employed calcium chloride, resulted in substantially greater yields of hybrids from intraspecific fusions of protoplasts of Saccharomyces cerevisiae and Candida albicans. It is postulated that the ability of calcium propionate to enhance the fusion frequency is due to the anion binding to the etheric oxygen of PEG and potentiating the fusogenicity of the polymer. PMID- 1916227 TI - A novel method for detection and counting of single bacteria in a wide field using an ultra-high-sensitivity TV camera without a microscope. AB - We describe a novel method for enumeration of bacteria, based on the principle that small, light emitting particles on a flat surface can be easily and rapidly detected and counted using an ultra-high-sensitivity TV camera. To test this method, we obtained TV images of individual cells of a luminous bacterium on a membrane filter without the use of a microscope. The positions of the luminous points in the TV images were almost the same as the positions of the bacterial colonies after growth. Our results show that the single cells can be efficiently detected and counted by our method if they emit light or can be stimulated to emit light. PMID- 1916228 TI - Comparative study of lipopolysaccharides from Wolinella recta, W. curva, W. succinogenes and Campylobacter sputorum ssp. sputorum. AB - Lipopolysaccharides (LPS) were extracted from cells of Wolinella recta ATCC 33238, W. curva ATCC 33224, W. succinogenes ATCC 29543 and Campylobacter sputorum ssp. sputorum A 3563 by a hot phenol-water method and purified by nuclease treatment and by repeated ultracentrifugation. Chemical compositions of the purified LPS including fatty acid and sugar composition were examined and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed. All LPS preparations contained a monosaccharide identified as L-glycero-D mannoheptose, and another heptose isomer identified as D-glycero-D-mannoheptose was a typical constituent of the LPS from all three Wolinella species. PMID- 1916229 TI - Analysis of the human serological response to Chlamydia trachomatis 60-kDa proteins by two-dimensional electrophoresis and immunoblotting. AB - Earlier analyses of sera from humans and animals with chlamydial infections demonstrated a strong immune response to proteins of approximately 60 kDa. We have used two-dimensional (2D) electrophoresis followed by immunoblotting to more accurately define patient responses to the chlamydial 60-kDa cysteine-rich envelope protein (OMP2) and to the 57-kDa stress protein (SP) implicated in immunopathological damage. OMP2 and SP were separated on 2D gels by their distinct isoelectric points and identified by fluorography of [35S]-labelled proteins and cross-reaction with anti-mycobacterial antiserum, respectively. The majority of patients sera showed a strong reaction both to OMP2 and the SP (18/20 and 17/20 sera, respectively). Fewer sera (9/20 and 10/20 sera, respectively) reacted with two other polypeptides also present in the 60-kDa range by this analysis. PMID- 1916230 TI - Construction and evaluation of a cea-lacZ gene fusion for the detection of environmental mutagens and carcinogens. AB - The cea-kil operon of the ColE1 plasmid is negatively regulated by the LexA repressor and therefore, it is under the control of SOS regulation. We constructed a gene fusion between the cea and lacZ genes. Expression of the translational fusion can be easily detected by monitoring the levels of beta galactosidase. Since the whole detection system is plasmid-based, it can be used in both Escherichia coli and Salmonella typhimurium strains. The SOS-function inducing activities of 14 chemical mutagens were investigated in E. coli K12 and in two S. typhimurium Ames-strains and compared with results obtained by the SOS chromotest and by the Umu-test. To correct for the inhibitory effects of test chemicals on mRNA and/or protein synthesis, the level of the constitutive chloramphenicol acetyl transferase was assayed in parallel. PMID- 1916231 TI - Production of monoclonal antibody to Clostridium difficile toxin A which neutralizes enterotoxicity but not haemagglutination activity. AB - Nine monoclonal antibodies (mAb) to Clostridium difficile toxin A were produced. The isotype of one mAb (37B5) was IgG2b, kappa, and that of the other eight mAbs was IgM, kappa. Immunoblot analysis after non-denatured PAGE showed that with the exception of one mAb (112G6) all mAbs gave a positive reaction with the 540 kDa band of toxin A. Immunoblot analysis showed that four mAbs (2E15, 3B4, 37B5 and 49C4) gave a positive reaction with the 240 kDa major band of toxin A. In neutralisation tests with these mAbs for enterotoxicity, mouse lethality, haemagglutination activity and cytotoxicity, 37B5 neutralised enterotoxicity in a rabbit ileal loop response test but did not neutralise any other biological activities. None of the other eight mAbs showed any neutralising activities at all. PMID- 1916232 TI - Antigenic relationships among the rickettsiae of the spotted fever and typhus groups. AB - Using immunoblots to analyze antigenic relationships among the pathogenic spotted fever and typhus group rickettsiae, I found that the rickettsial lipopolysaccharide (LPS) was a group-specific antigen. All the rickettsiae examined had 135-kDa and 58-kDa protein antigens. The spotted fever rickettsiae and Rickettsia canada had, in addition, 190-kDa protein antigens which were antigenic analogs of previously described protective antigens of R. conorii and R. rickettsii. PMID- 1916233 TI - Lack of specific hybridization between the lep genes of Salmonella typhimurium and Bacillus licheniformis. AB - This paper describes an attempt to clone the Bacillus licheniformis lep gene, encoding signal peptidase, using the Salmonella typhimurium lep gene as a hybridization probe. Although a hybridizing fragment was obtained, DNA sequence analysis indicated that it did not contain the lep gene. Instead, the protein encoded by the cloned fragment showed similarity with a variety of L asparaginases. PMID- 1916234 TI - Can dietary intake patterns account for the familial aggregation of disease? Evidence from adult siblings living apart. AB - The familial aggregation of certain chronic diseases is well documented [Perkins, 1986; King et al., 1984; Anderson, 1982]. Dietary data on adult brothers living apart were used to examine whether familial clustering of disease could be explained by nature or nutriture. Intakes of nutrients were strikingly more similar among siblings than expected: when correlations were adjusted for country of residence, 21 of 25 (84%) were statistically significant. Thus, dietary patterns among adult siblings are more alike than could be predicted by their sharing a common culture, as alike as has been described for monozygotic twins, and as alike as described for familial correlations of serum cholesterol. Incorporation of dietary measures in co-twin studies or studies of siblings can improve the estimates of the true genetic effect on disease pathogenesis. PMID- 1916236 TI - A powerful test of sib-pair linkage for disease susceptibility. PMID- 1916235 TI - A variance components/major locus likelihood approximation on quantitative data. AB - The variance components/major locus model encompasses a major locus, a polygenic component, and shared environmental effects. The model attributes familial correlations to polygenic and shared environmental effects when testing for major locus inheritance or accounts for the major locus when estimating variance components. Because exact computation of the likelihood of the variance components/major locus model on quantitative data requires excessive computer time, I developed an approximation. The approximation retained the general shape of the likelihood surface. Accuracy of the approximation did not vary consistently with allele frequency or the size of the major locus effect. PMID- 1916237 TI - Mixed model segregation analysis of LDL-C concentration with genotype-covariate interaction. AB - Mixed model complex segregation analyses have in the past ignored the possibility of genotype-covariate interaction. Only in the nonmixed model with polygenic heritability equal to zero have segregation analyses been performed that allowed for genotype specific regression of the phenotype on covariates. We present an extension of Hasstedt's [1982] mixed model likelihood approximation which does allow for genotype-covariate interaction in the mixed model. Following description of this approximation, we validate the likelihood calculation by a Monte Carlo procedure based on the actual pedigree and missing data structure used in a complex segregation analysis of low density plus very low density lipoprotein cholesterol (LDL-C + VLDL-C) in baboons. The observed averages of the bootstrap parameter estimates adequately recover the generating values, which included parameters specifying genotype-covariate interaction. We then applied both a traditional complex segregation analysis and an analysis with genotype covariate interaction to test for the presence of a major locus affecting LDL-C levels in baboons. The model including genotype-covariate interaction was significantly different from the model without interactions, and strongly supported the hypothesis that there is a segregating Mendelian locus as opposed to a random environmental factor. This major locus accounts for approximately 46% of the variance in LDL-C levels, as compared to 40% explained by a locus with no genotype-covariate interaction. PMID- 1916238 TI - Efficient methods for computing linkage likelihoods of recessive diseases in inbred pedigrees. AB - Traditional methods for computing linkage likelihoods can be infeasible for data that involve considerable inbreeding and missing information, characteristics of large pedigrees affected by rare recessive diseases. For this type of data, we propose alternative procedures that can efficiently provide good approximates of linkage likelihoods. These approximation procedures are constructed based on a new mathematical representation of the multiloci inheritance model. Instead of representing each person by a single variable, the genotype, the disease gene alleles, and the marker alleles are taken as separate variables. This allows us to break down the computations into manageable pieces. This new representation is also potentially useful for multipoint mapping. PMID- 1916239 TI - Twenty-five years ago in Genetics: electrophoresis in the development of evolutionary genetics: milestone or millstone? PMID- 1916240 TI - Marker-dependent recombination in T4 bacteriophage. III. Structural prerequisites for marker discrimination. AB - Distance- as well as marker-dependence of genetic recombination of bacteriophage T4 was studied in crosses between rIIB mutants with known base sequences. The notion of a "basic recombination," which is the recombination within distances shorter than hybrid DNA length in the absence of mismatch repair and any marker effects, was substantiated. The basic recombination frequency per base pair can serve as an objective parameter (natural constant) of general recombination reflecting its intensity. Comparative studies of the recombination properties of rIIB mutants with various sequence changes in the mutated sites showed that the main factor determining the probability of mismatch repair in recombination heteroduplexes is the length of a continuous heterologous region. A run of A:T pairs immediately adjoining the mismatch appears to stimulate its repair. In the case of mismatches with DNA strands of unequal length, formed by frameshift mutations, the repair is asymmetric, the longer strand (bulge) being preferentially removed. A pathway for mismatch repair including sequential action of endonuclease VII (gp49)----3'----5' exonuclease (gp43)----DNA polymerase (gp43)----DNA ligase (gp30) was proposed. A possible identity of the recombinational mismatch repair mechanism to that operating to produce mutations via sequence conversion is discussed. PMID- 1916241 TI - Adaptive reversion of a frameshift mutation in Escherichia coli. AB - Mutation rates are generally thought not to be influenced by selective forces. This doctrine rests on the results of certain classical studies of the mutations that make bacteria resistant to phages and antibiotics. We have studied a strain of Escherichia coli which constitutively expresses a lacI-lacZ fusion containing a frameshift mutation that renders it Lac-. Reversion to Lac+ is a rare event during exponential growth but occurs in stationary cultures when lactose is the only source of energy. No revertants accumulate in the absence of lactose, or in the presence of lactose if there is another, unfulfilled requirement for growth. The mechanism for such mutation in stationary phase is not known, but it requires some function of RecA which is apparently not required for mutation during exponential growth. PMID- 1916242 TI - Genetic variance for body size in a natural population of Drosophila buzzatii. AB - Previous work has shown thorax length to be under directional selection in the Drosophila buzzatii population of Carboneras. In order to predict the genetic consequences of natural selection, genetic variation for this trait was investigated in two ways. First, narrow sense heritability was estimated in the laboratory F2 generation of a sample of wild flies by means of the offspring parent regression. A relatively high value, 0.59, was obtained. Because the phenotypic variance of wild flies was 7-9 times that of the flies raised in the laboratory, "natural" heritability may be estimated as one-seventh to one-ninth that value. Second, the contribution of the second and fourth chromosomes, which are polymorphic for paracentric inversions, to the genetic variance of thorax length was estimated in the field and in the laboratory. This was done with the assistance of a simple genetic model which shows that the variance among chromosome arrangements and the variance among karyotypes provide minimum estimates of the chromosome's contribution to the additive and genetic variances of the trait, respectively. In males raised under optimal conditions in the laboratory, the variance among second-chromosome karyotypes accounted for 11.43% of the total phenotypic variance and most of this variance was additive; by contrast, the contribution of the fourth chromosome was nonsignificant. The variance among second-chromosome karyotypes accounted for 1.56-1.78% of the total phenotypic variance in wild males and was nonsignificant in wild females. The variance among fourth chromosome karyotypes accounted for 0.14-3.48% of the total phenotypic variance in wild flies. At both chromosomes, the proportion of additive variance was higher in mating flies than in nonmating flies. PMID- 1916243 TI - Genetic analysis of chromosome region 63 of Drosophila melanogaster. AB - The salivary chromosome region including cytological division 63 of Drosophila melanogaster was genetically analyzed in order to (1) characterize this previously unstudied region and (2) attempt to isolate mutations in the hsp82 gene. Seven deletions which span this region were isolated, including four which remove the hsp82 gene. A Minute mutation was mapped to this region and this Minute was used to isolate duplications in the 63 region. These duplications map the Minute to 63B8-C1. F2 screens were initiated using deletions which remove the hsp82 gene. Over 15,000 chromosomes were screened, yielding 40 lethal mutations which comprise 14 complementation groups. Several of these mutations map outside the 63 region and appear to give second site interaction with the Minute locus. Four loci, including the Minute gene, are candidates for hsp82 mutations by cytogenetic mapping. These loci were tested for complementation with a P element carrying the hsp82 gene. However, none of the mutations was rescued. PMID- 1916244 TI - The effect of modifiers of position-effect variegation on the variegation of heterochromatic genes of Drosophila melanogaster. AB - Dominant modifiers of position-effect variegation of Drosophila melanogaster were tested for their effects on the variegation of genes normally located in heterochromatin. These modifiers were previously isolated as strong suppressors of the variegation of euchromatic genes and have been postulated to encode structural components of heterochromatin or other products that influence chromosome condensation. While eight of the modifiers had weak or no detectable effects, six acted as enhancers of light (lt) variegation. The two modifiers with the strongest effects on lt were shown to also enhance the variegation of neighboring heterochromatic genes. These results suggest that the wild-type gene products of some modifiers of position-effect variegation are required for proper expression of genes normally located within or near the heterochromatin of chromosome 2. We conclude that these heterochromatic genes have fundamentally different regulatory requirements compared to those typical of euchromatic genes. PMID- 1916245 TI - Genetic exchange across a paracentric inversion of the mouse t complex. AB - Mouse t haplotypes are distinguished from wild-type forms of chromosome 17 by four nonoverlapping paracentric inversions which span a genetic distance of 20 cM. These inversion polymorphisms are responsible for a 100-200-fold suppression of recombination which maintains the integrity of complete t haplotypes and has led to their divergence from the wild-type chromosomes of four species of house mice within which t haplotypes reside. As evidence for the long period of recombinational isolation, alleles that distinguish all t haplotypes from all wild-type chromosomes have been established at a number of loci spread across the 20-cM variant region. However, a more complex picture emerges upon analysis of other t-associated loci. In particular, "mosaic haplotypes" have been identified that carry a mixture of wild-type and t-specific alleles. To investigate the genetic basis for mosaic chromosomes, we conducted a comprehensive analysis of eight t complex loci within 76 animals representing 10 taxa in the genus Mus, and including 23 previously characterized t haplotypes. Higher resolution restriction mapping and sequence analysis was also performed for alleles at the Hba-ps4 locus. The results indicate that a short tract of DNA was transferred relatively recently across an inversion from a t haplotype allele of Hba-ps4 to the corresponding locus on a wild-type homolog leading to the creation of a new hybrid allele. Several classes of wild-type Hba-ps4 alleles, including the most common form in inbred strains, appear to be derived from this hybrid allele. The accumulated data suggest that a common form of genetic exchange across one of the four t-associated inversions is gene conversion at isolated loci that do not play a role in the transmission ratio distortion phenotype required for t haplotype propagation. The implications of the results pose questions concerning the evolutionary stability of gene complexes within large paracentric inversions and suggest that recombinational isolation may be best established for loci residing within a short distance from inversion breakpoints. PMID- 1916247 TI - The structure of genealogies and the distribution of fixed differences between DNA sequence samples from natural populations. AB - When two samples of DNA sequences are compared, one way in which they may differ is in the presence of fixed differences, which are defined as sites at which all of the sequences in one sample are different from all of the sequences in a second sample. The probability distribution of the number of fixed differences is developed. The theory employs Wright-Fisher genealogies and the infinite sites mutation model. For the case when both samples are drawn randomly from the same population it is found that genealogies permitting fixed differences are very unlikely. Thus the mere presence of fixed differences between samples is statistically significant, even for small samples. The theory is extended to samples from populations that have been separated for some time. The relationship between a simple Poisson distribution of mutations and the distribution of fixed differences is described as a function of the time since populations have been isolated. It is shown how these results may contribute to improved tests of recent balancing or directional selection. PMID- 1916246 TI - Interspecific backcross mice show sex-specific differences in allelic inheritance. AB - Transmission distortion is identified as a difference in transmission frequency of two alleles from the normal 1:1 Mendelian segregation in diploid organisms. Transmission distortion can extend over part or all of a chromosome. The recent development of interspecific mouse backcrosses has provided a powerful method for multilocus mapping of entire chromosomes in a single cross, and consequently for identifying distortions in allelic inheritance. We used an interspecific backcross of [(C57BL/6J x Mus spretus)F1 x C57BL/6J] mice to map molecular loci to mouse chromosome 2 and had previously found that the distal region of the chromosome showed distortions in allelic inheritance. We now report the mapping of five loci (Actc-1, D2Hgu1, His-1, Hox-4.1 and Neb) to chromosome 2, which, in addition to the Abl, Ada, B2m, Bmp-2a, Hc, Emv-15, Fshb, Hck-1, Pax-1, Pck-1, Spna-2 and Vim loci previously mapped in our interspecific backcross, serve as markers to measure allelic inheritance along approximately 75% of mouse chromosome 2. Statistical analyses are used to identify and delimit chromosomal regions showing transmission distortion and to determine whether there are sex specific differences in allelic inheritance. These studies provide evidence for sex-specific differences in allelic inheritance for chromosome 2 and suggest biological explanations for this form of transmission distortion. PMID- 1916248 TI - Causes of sex ratio bias may account for unisexual sterility in hybrids: a new explanation of Haldane's rule and related phenomena. AB - Unisexual hybrid disruption can be accounted for by interactions between sex ratio distorters which have diverged in the species of the hybrid cross. One class of unisexual hybrid disruption is described by Haldane's rule, namely that the sex which is absent, inviable or sterile is the heterogametic sex. This effect is mainly due to incompatibility between X and Y chromosomes. We propose that this incompatibility is due to a mutual imbalance between meiotic drive genes, which are more likely to evolve on sex chromosomes than autosomes. The incidences of taxa with sex chromosome drive closely matches those where Haldane's rule applies: Aves, Mammalia, Lepidoptera and Diptera. We predict that Haldane's rule is not universal but is correct for taxa with sex chromosome meiotic drive. A second class of hybrid disruption affects the male of the species regardless of which sex is heterogametic. Typically the genes responsible for this form of disruption are cytoplasmic. These instances are accounted for by the release from suppression of cytoplasmic sex ratio distorters when in a novel nuclear cytotype. Due to the exclusively maternal transmission of cytoplasm, cytoplasmic sex ratio distorters cause only female-biased sex ratios. This asymmetry explains why hybrid disruption is limited to the male. PMID- 1916249 TI - [Induction of unstable mutations in Drosophila melanogaster by microinjection of oncogenic virus DNA into polar embryonic plasm. Malignant effect of oncoviral DNA]. AB - We have demonstrated that the ability to induce benign neoplasms We have dominant mode of inheritance in Drosophila melanogaster is the specific feature of oncoviral DNAs. It is supposed that development of this type of neoplasms in Drosophila is connected with the changes in expression of protooncogenes in mutant genome: firstly, the genetic factors directing the development of neoplasms and Drosophila protooncogenes which shared the homology with v-src are localised in the same regions; secondly, there are structural rearrangements in c src/fps (29A) protooncogene in mutant stocks which display the ability for neoplastic growth. PMID- 1916250 TI - [Features of transformation of competent cells and Bacillus subtilis protoplasts by integrative vectors]. AB - The effect of structural peculiarities of DNAs from integrative plasmids on the transformation activity was studied. Monomeric forms of the plasmids can only transform B. subtilis competent cells, when plasmid selective marker is inserted into chromosomal fragment within the plasmid. Polymeric forms are needed for efficient transformation. Both single- and double-stranded DNAs of integrative plasmids transform no B.subtilis protoplasts, this being irrespective of plasmid structure. PMID- 1916251 TI - [Chromosomal control of chiasma distribution in house mice. Analysis of chiasma distribution in homo- and heterozygotes by inversion in chromosome 1]. AB - Examination of chiasma distribution in the chromosome 1 in male mice homo- and heterozygous for distal inversion In(1)12Rk and in normal mice was carried out. No differences in chiasma distribution was found between homozygotes for the inversion and homozygotes for normal chromosome 1. A drastic change in this trait was revealed in heterozygous animals. In heterozygotes, the telomeric segments of SC were asynapsed and unavailable for recombination. This leads to significant decrease in the frequency of bivalents bearing chiasmata in pretelomeric region. In turn, it produced chiasma redistribution in proximal noninverted portion of the bivalent 1. These results could be interpreted as evidence for chromosomal control of chiasma distribution pattern: the distance of certain part of the chromosome from telomere and interference (which also operates at the chromosomal level) are more important for determination of the chiasmata frequency in the given region, than its genetic content. PMID- 1916252 TI - [Systemic reorganization of the architechtonics of polytene chromosomes in onto- and phylogenesis of malaria mosquitoes. Structural features regional of chromosomal adhesion to the nuclear membrane]. AB - Principles of organization of chromocenter in salivary gland cells and zones of chromosome attachment to nuclear envelope in ovarian nurse cells were determined. It was shown that blocks of centromeric heterochromatin (alfa-heterochromatin) have no direct connection with nuclear envelope. Such connections are ensured by beta-heterochromatin. Homologous chromosome regions were shown to be of different morphology and nature of chromosome-membrane links in different mosquito species. A map of polytene chromosomes of ovarian nurse cells in Anopheles messeae Fall, was established. No differences were found in band quantity of these chromosomes as compared to salivary gland chromosomes. PMID- 1916253 TI - [Chromosomal restructuring of three species of chiromonads from the Chernobyl region (Diptera, Chironomidae)]. AB - Chromosomal polymorphism of three species--Chironomus plumosus, Ch. balatonicus and Glyptotendipes glaucus collected from the Chernobyl Zone demonstrated following characteristics: lack of standard karyotype, the presence of hetero- and homozygotic inversions (seven para- and one pericentric), increase in centromeric heterochromatin (55% larvae in homo- and heterozygotic state), the presence of B chromosomes (21%)--in Ch. plumosus; only two larvae had a standard karyotype, the rest demonstrating hetero- and homozygotic inversions (eleven paracentrics), reciprocal translocations of the IVF and IA arms, B chromosomes (5.4%), increase in telomeric (43.6%) and centromeric (1.8%) heterochromatin--in Ch. balatonicus; two types of hetero- and homozygotic inversions, replacement of standard sequences in C and D for inversional homozygotic ones--in Gl. glaucus. PMID- 1916254 TI - [Methodological approach to genetic-selection analysis of social behavior of animals (Using as an example domestic behavior of the silver fox)]. AB - Social behaviour of animals, i.e. interspecies contacts, were studied in a population of silver foxes in the longitudinal model domestication experiment. Three social behaviour traits were analysed: contactibility, critical distance and domestication index. The latter trait is a linear function of elementary behaviour reactions, postures induced by man which is determined by the principal components method. The most valiable selection phenotype for further modelling of domestication, as shown by the capacity to adequately reflect a pattern of genotype--environment interaction, the structure of correlation ratios for different forms of behaviour and the level of genetic relationships between relatives, is the domestication index. PMID- 1916255 TI - [Activation of expression of two immunoglobulin SN-genes in the American mink with Aleutian disease]. AB - 110 ranch-raised minks were injected with the Aleutian disease virus. Allotypes of constant regions of gamma-heavy chains of the mink immunoglobulins secreted have been analysed during 3 months. Activation of the expression of two markers (H3 and/or H4) up to minor or to nominal level (above 200 micrograms/ml) was observed. No such enhancement of expression of two other allotypes (H6 and H8) was found. The results suggest that the expression of two mink immunoglobulin CH genes induced by viral infection has allotype-specific regulation. PMID- 1916256 TI - [Correction for the estimated load of hereditary diseases in the population of the Krasnodarsk district]. AB - Medico-genetical examination of children from 6 invalid houses, 2 asylum houses, 3 internate schools and 1 house for deaf and feeble-hearing children as well as from the internate school for children with poor vision was undertaken in Krasnodar district. 10.6% of the children were found to have chromosomal abnormality, 26.5%--multifactorial pathology and 62.9% of children were affected by monogenic diseases. The spectrum of diseases covers 20 forms, 8 of them being autosomal-dominant, 10--autosomal-recessive and 2--X-linked forms. A "selective" method presented in this article for revealing patients affected by genetical diseases in specialised institutions permitted to evaluate a portion of the patients having been not identified when using the "survey" expeditional method of population--epidemiological study of the district population. This portion constitutes 19%. The more accurate values of genetic load in populations of Krasnodar district were obtained, being 1.06-0.06 for autosomal-dominant, 0.78 0.05 for autosomal-recessive and 0.38-0.05 for X-linked diseases per thousand. PMID- 1916258 TI - [Marriage structure of residents of Kharkhov in relation to genetically significant socio-demographic characteristics]. AB - Positive assortative mating for education and profession has been revealed by means of sample analysis of couples married in two districts of Kharkov in 1960 and 1985. The contingency coefficient measuring the association between education of husband and wife in 1985 was K = 0.27 in one and K = 0.35 in the other district. The degree of assortative mating for profession was K = 0.57 and K = 0.19 in 1960, K = 0.27 and K = 0.31 in 1985, in two districts, respectively. PMID- 1916257 TI - [Load of hereditary diseases in the populations of the Adyg autonomic district]. AB - Comparative analysis of the loads of hereditary diseases in two ethnically different populations coexisting in the Adyg national district was performed. The modes of inheritance of diseases studied were tested by segregational analysis. The results obtained demonstrated that the load of autosomal-recessive diseases in the populations of the Adyg national district is higher than that in Russian population, while the load of autosomal-dominant diseases is similar in two populations. This difference in the level of the loads appear to be connected with genetic structure of the populations studied. Regressional analysis of relations between loads and the level of inbreeding in the Adyg population showed the explicit interrelation between the load of autosomal-dominant diseases and the Fst correlation coefficient being 0.89. PMID- 1916259 TI - [Significance of indices of potential selection for residents of the USSR]. AB - Crow's indices of the opportunity for selection and their components connected with differential mortality (Im) and differential fertility (If) were estimated for populations of Soviet Union republics and for a number of USSR ethnic groups on the basis of demographic statistics. More than 10-fold decrease in the Im value was revealed in the total population of the USSR during 1926-1987. At present, the Im values in republics vary from 0.020 to 0.094 for urban population and from 0.030 to 0.121 in rural population, the ratio of perinatal mortality in the whole structure of prereproductive mortality being higher in the republics with lower values of the Im. The range of the If values for different peoples (0.148-0.643) is wider than for the populations of the republics (0.326-0.578). Interethnic differences contribute 47% of the variance in fertility. The structure of Crow's indices is given for urban and rural populations of the republics. Genetic implications of the data presented are discussed with respect to possible manifestation of the effects of inter-group selection. PMID- 1916260 TI - [Hidden polyteny in giant embryonic nuclei of Drosophila melanogaster gnu mutants]. AB - Drosophila melanogaster embryos, whose mothers are homozygous for the gnu (a recessive lethal mutation with maternal effect) undergo DNA synthesis but are defective in nuclear division. This leads to formation of giant nuclei in the syncytial blastoderm. The interior spatial chromatin organization and possibility of obtaining polytene chromosomes in these nuclei was analysed. Partial conjugation of homologous chromatids, which is an evidence for cryptic polyteny in the gnu embryos nuclei, was shown. PMID- 1916261 TI - Is there a Xenopus transcription factor that can substitute for TFIIIA? Re: Two TFIIIA activities regulate expression of the Xenopus 5S RNA gene families. PMID- 1916262 TI - TEF, a transcription factor expressed specifically in the anterior pituitary during embryogenesis, defines a new class of leucine zipper proteins. AB - We have identified and characterized a new member of the leucine zipper (bZIP) gene family of transcription factors, thyrotroph embryonic factor (TEF). Analysis of the ontogeny of TEF gene expression reveals the presence of TEF transcripts, beginning on embryonic day 14, only in the region of the rat anterior pituitary gland in which thyrotrophs arise. This pattern of gene expression corresponds temporally and spatially to the onset of thyroid-stimulating hormone (TSH beta) gene expression, which defines the thyrotroph phenotype. Coupled with this observation, we find that TEF can bind to and trans-activate the TSH beta promoter. In contrast to this restricted pattern of expression during embryogenesis, TEF transcripts appear in several tissues in the mature organism. We propose that TEF belongs to a new class of bZIP proteins on the basis of the unique homology between TEF and another member of the bZIP gene family, the albumin D box-binding protein (DBP). TEF and DBP transcripts are coexpressed in a pituitary cell line, and these two proteins can readily form heterodimers. The DNA-binding and dimerization domains of TEF correspond to those found in other bZIP proteins. We have however, identified a cluster of basic amino acids, found only in TEF and DBP, that is necessary for the proper DNA-binding site specificity of TEF. A major trans-activation domain of TEF resides outside the region of homology to other bZIP proteins. These data are consistent with a role for a member of a new class of bZIP transcription factors in activating gene expression in the developing thyrotroph. PMID- 1916263 TI - Chromosome tangling and breakage at anaphase result from mutations in lodestar, a Drosophila gene encoding a putative nucleoside triphosphate-binding protein. AB - We describe a Drosophila maternal-effect gene, lodestar, mutations in which cause chromatin bridges at anaphase. lodestar maps to cytological position 84D13-14, and we identified the lodestar gene in germ-line transformation experiments by the ability of a genomic fragment to restore fertility to females homozygous for lodestar mutations. lodestar encodes a potential nucleoside triphosphate binding protein, which is a novel member of the D-E-A-H box family of proteins. Antibodies raised against the lodestar gene product detect a protein that undergoes cell cycle-dependent changes in distribution in the embryo. The protein is cytoplasmic at interphase, and rapidly enters the nucleus early in prophase. It is restricted to the region enclosed by the spindle envelope during metaphase and anaphase; but by telophase, the lodestar protein is contained entirely within the reforming nucleus. PMID- 1916264 TI - Negative regulatory sequences in the lin-14 3'-untranslated region are necessary to generate a temporal switch during Caenorhabditis elegans development. AB - The heterchronic gene lin-14 controls the temporal sequence of developmental events in the Caenorhabditis elegans postembryonic cell lineage. It encodes a nuclear protein that normally is present in most somatic cells of late embryos and L1 larvae but is absent at later stages. Two lin-14 gain-of-function mutations delete 3'-untranslated sequences causing an inappropriately high level of the lin-14 nuclear protein late in development. These mutations identify a negative regulatory element that controls the formation of the lin-14 protein temporal gradient. The 21-kb lin-14 gene is differentially spliced to generate three lin-14 transcripts that encode protein products with variable amino terminal regions and a constant carboxy-terminal region. The sequence of the gene revealed no protein sequence similarity to any proteins in various data bases. PMID- 1916265 TI - Temporal regulation of lin-14 by the antagonistic action of two other heterochronic genes, lin-4 and lin-28. AB - Heterochronic genes form a regulatory pathway that controls the temporal sequence of the Caenorhabditis elegans postembryonic cell lineage. One of these genes, lin 14, encodes a nuclear protein that constitutes a temporal developmental switch. During wild-type development, lin-14 protein is abundant during early larval stage 1 (L1) to specific L1-specific cell lineages but is nearly undetectable at L2 and later stages to specify L2-specific and later cell lineages. To determine the roles played by other genes in executing this temporal switch, we have analyzed how lin-14 expression is regulated by other heterochronic genes. lin-4 is required to down-regulate lin-14 protein levels during the L1 stage, whereas lin-28 positively regulates lin-14 protein levels. The lin-4 gene product is a candidate for interacting with the negative regulatory element in the 3' untranslated region of lin-14. lin-29 mutations do not affect lin-14 protein levels, consistent with lin-29 acting downstream of lin-14. Switching off lin-14 expression during the L1 stage is not triggered by the passage of time per se but, rather, is normally dependent on feeding or the feeding-dependent initiation of postembryonic cell division. PMID- 1916266 TI - Binding of the CBP2 protein to a yeast mitochondrial group I intron requires the catalytic core of the RNA. AB - The yeast CBP2 gene product is required for the splicing of the terminal intron (bI5) of the mitochondrial cytochrome b pre-mRNA in vivo. In vitro, bI5 RNA self splices efficiently only at high MgCl2 concentrations (50 mM); at 5 mM MgCl2, efficient splicing requires purified CBP2 protein. To determine the sequences within bI5 recognized by the protein, we have constructed deletion and substitution mutants of the RNA. Their binding to CBP2 was assessed by their ability to inhibit protein-dependent splicing of the wild-type bI5 RNA. Several regions, including the large L1 and L8 loops, can be deleted without affecting binding. They can therefore be eliminated from consideration as critical recognition elements. In contrast, other changes prevent the RNA from binding CBP2 and also impair self-splicing. Thus, either the catalytic core contacts the protein directly, or the integrity of the core is required for proper display of other RNA sequences that bind the protein. The results are consistent with a model in which the CBP2 protein facilitates splicing by binding to and stabilizing the active structure of the RNA. However, a more specific model is proposed in which the protein specifically enhances Mg2+ binding required for catalysis. PMID- 1916267 TI - MAT alpha 1 can mediate gene activation by a-mating factor. AB - In the yeast Saccharomyces cerevisiae, expression of alpha-specific genes is governed by the MAT alpha 1 and MCM1 gene products. MAT alpha 1 and MCM1 bind cooperatively to PQ elements upstream of alpha-specific genes. The PQ element not only directs alpha-specific expression but can also direct gene induction in response to treatment with a-mating pheromone. We have used gene fusions to investigate whether induction conferred by the PQ box is mediated through either MAT alpha 1 or MCM1, or a combination of both. When MCM1 is fused to the DNA binding domain of the bacterial repressor LexA, this fusion protein is capable of trans-activating a lacZ reporter gene driven by a LexA operator. However, the transcriptional activity of the MCM1-LexA fusion is not further enhanced by treatment of cells with a-factor. A MAT alpha 1-LexA fusion protein is also capable of trans-activation through a LexA operator. Moreover, the activity of the MAT alpha 1-LexA fusion protein can be further induced by treatment with a factor. When progressive deletions are made from the amino terminus of MAT alpha 1 in the fusion protein, the basal level of trans-activation progressively decreases, but the inducibility of the fusion protein increases. MAT alpha 1-LexA fusion proteins, which have greater than or equal to 57 amino acids deleted from the amino terminus of MAT alpha 1 are not capable of trans-activation. In addition, the activity of the MAT alpha 1-LexA fusion protein is dependent on the functions of the STE7, STE11, and STE12 genes that encode components of the pheromone response pathway. PMID- 1916268 TI - Nucleotide sequence of a cluster of genes involved in the transformation of Haemophilus influenzae Rd. AB - A genetic locus implicated in the development of competence in Haemophilus influenzae Rd has been previously mapped to a 12.8-kb PstI region of the chromosome [Tomb et al., J. Bacteriol. 171 (1989) 3796-3802]. To define the boundaries of this locus and to identify the gene(s) involved in transformation, additional mini-Tn10kan mutagenesis was performed and the region containing all mutagenic insertions was sequenced. Three new transformation-deficient (Tfo-) mutants were found, bringing the number of distinct mutations mapped to this region up to eight. The transformation frequency of strains carrying the new insertions was 25- to 10(5)-fold less than wild type. The ends of the mini Tn10kan element were used as starting points to sequence a 9.1-kb region. The position of the eight mutagenic insertions was determined and ten putative open reading frames (ORFs) were found. One of the mini-Tn10kan elements had inserted in an intergenic region while the rest had inserted in six of the ORFs. Based on the phenotypes of the mutant strains and the position of the insertions, we concluded that at least three of the genes should be involved in transformation. In addition, fourteen 9-11-bp uptake signal sequences (USS) were found, four of which were part of stem-loop structures and could function as attenuators of terminators of transcription. PMID- 1916269 TI - Sequence of RAD54, a Saccharomyces cerevisiae gene involved in recombination and repair. AB - The complete nucleotide sequence of the RAD54 gene of the yeast Saccharomyces cerevisiae has been determined. The sequenced region contains an open reading frame of 2694 bp, and the predicted RAD54 protein has a potential nucleotide binding site and possible nuclear targeting sequences. Northern analysis reveals a transcript of approx. 3.0 kb which is induced following x-ray irradiation. PMID- 1916270 TI - Improved shuttle vectors for cloning and high-level Cu(2+)-mediated expression of foreign genes in yeast. AB - New yeast episomal vectors having a high degree of utility for cloning and expression in Saccharomyces cerevisiae are described. One vector, pYEULlacZ, is based on pUC19 and employs the pUC19 multiple cloning site for the selection of recombinants in Escherichia coli by lacZ inactivation. In addition, the vector contains two genes, URA3 and leu2-d, for selection of the plasmid in ura3 or leu2 yeast strains. The presence of the leu2-d gene appears to promote replication at high copy numbers. The introduction of CUP1 cassettes allows these plasmids to direct Cu(2+)-regulated production of foreign proteins in yeast. We show the production of a helminth antigen as an example of the vector application. PMID- 1916271 TI - A twin-reporter vector for simultaneous analysis of expression signals of divergently transcribed, contiguous genes in filamentous fungi. AB - To analyze the promoter region(s) of divergently transcribed fungal genes, a twin reporter vector was constructed. This vector contains two divergently oriented reported genes, encoding Escherichia coli beta-glucuronidase (uidA) and E. coli beta-galactosidase (lacZ). Terminator regions of the Aspergillus nidulans nitrate and nitrite reductase-encoding genes, niaD and niiA, respectively, have been cloned 3' to the reporter genes to ensure proficient transcription termination of the reporter genes. The reporter genes have been separated by a unique NotI restriction site, which can be used for the insertion of expression signals. A mutant argB selection marker has been introduced in order to obtain A. nidulans transformants with a single copy of the vector integrated at the argB locus. The use of the vector was demonstrated by insertion of the A. nidulans niaD-niiA intergenic region and analysis of A. nidulans transformants obtained with this construct. Control of expression of both reporter genes was found to be in accordance with previously published data on control of nitrate assimilation [Cove, Biol. Rev. 54 (1979) 291-327]. PMID- 1916272 TI - The nucleotide sequence of rpsL and its flanking regions in Salmonella typhimurium. AB - The ribosomal protein (r-protein)-encoding gene, rpsL, and regions flanking it, from Salmonella typhimurium, have been sequenced directly from polymerase chain reaction-amplified chromosomal DNA. The deduced amino acid sequence is identical to that of the Escherichia coli rpsL encoded r-protein. At the nucleotide level, the similarity is 98%, suggesting a strong pressure for the conservation of this important protein. More surprisingly, the noncoding sequences surrounding the gene are also conserved at the 98% level, suggesting that they too are functionally important. PMID- 1916273 TI - High-level synthesis of active adenylate cyclase toxin of Bordetella pertussis in a reconstructed Escherichia coli system. AB - The Bordetella pertussis adenylate cyclase(Cya) toxin-encoding locus (cya) is composed of five genes. The cyaA gene encodes a virulence factor (CyaA), exhibiting adenylate cyclase, hemolytic and invasive activities. The cyaB, D and E gene products are necessary for CyaA transport, and the cyaC gene product is required to activate CyaA. We reconstructed, in Escherichia coli, the cya locus of B. pertussis by cloning the different genes on appropriate vectors under the control of strong promoters and E. coli-specific translation initiation signals. We show that in the absence of additional gene products, CyaA is synthesized at high levels, is endowed with adenylate cyclase activity, but is devoid of invasive and hemolytic activities. CyaC is sufficient to confer upon the adenylate cyclase holotoxin full invasive and partial hemolytic activities. Coexpression of the cyaB, D and E genes neither stimulates nor potentiates the activation brought about by CyaC. This reconstructed system should help to elucidate both the mechanism and the structural requirements of holotoxin activation. PMID- 1916274 TI - Sequence of the lyc gene encoding the autolytic lysozyme of Clostridium acetobutylicum ATCC824: comparison with other lytic enzymes. AB - The lyc gene, encoding an autolytic lysozyme from Clostridium acetobutylicum ATCC824, has been cloned. The nucleotide sequence of the lyc gene has been determined and found to encode a protein of 324 amino acids (aa) with a deduced Mr of 34,939. The lyc gene is preceded by two open reading frames with unknown functions, suggesting that this gene is part of an operon. Comparison between the deduced aa sequence of the lyc gene and the directly determined N-terminal sequence of the extracellular clostridial lysozyme suggests that the enzyme is synthesized without a cleavable signal peptide. Moreover, the comparative analyses between the clostridial lysozyme and other known cell-wall lytic enzymes revealed a significant similarity with the N-terminal portion of the lysozymes of Streptomyces globisporus, the fungus Chalaropsis, the Lactobacillus bulgaricus bacteriophage mv1, and the Streptococcus pneumoniae bacteriophages of the Cp family (CPL lysozymes). In addition, the analyses showed that the C-terminal half of the clostridial lysozyme was homologous to the N-terminal domain of the muramoyl-pentapeptide-carboxypeptidase of Streptomyces albus, suggesting a role in substrate binding. The existence of five putative repeated motifs in the C terminal region of the autolytic lysozyme suggests that this region could play a role in the recognition of the polymeric substrate. PMID- 1916275 TI - Nucleotide sequence analysis of the endoglucanase-encoding gene, celCCD, of Clostridium cellulolyticum. AB - The nucleotide sequence of the Clostridium cellulolyticum endo-beta-1,4- glucanase (EGCCD)-encoding gene, celCCD, and its flanking regions, was determined. The open reading frame encodes a protein (Mr 66,061) which consists of 584 amino acids (aa). The N terminus shows the features of the typical signal peptide, with a cleavage site after Gly24. The protein could be divided into N terminal and C-terminal regions by an intermediate Pro + Thr-rich sequence. Deletion analysis suggests the C-terminal region is not necessary for EG activity. The predicted aa sequence of the mature protein was similar to those of the central catalytic and the following C-terminal regions of the C. thermocellum endoglucanase H (EGH; identity, 58.8%). The N-terminal region resembled that of the endoglucanase, EGCCA, from C. cellulolyticum (identity, 24.7%; 336 aa) and the endoglucanase, EGE, from C. thermocellum (identity, 31.4%; 373 aa). The C terminal regions ended with two conserved 21-aa stretches which had close similarity to each other. The C-terminal sequence was also highly similar to the reiterated domain of several EG and a xylanase from C. thermocellum, and of an EG from C. cellulolyticum. PMID- 1916276 TI - Characterization of a gene conferring bialaphos resistance in Streptomyces coelicolor A3(2). AB - A gene (bar) was identified adjacent to the hrdD sigma factor gene in Streptomyces coelicolor A3(2). The predicted bar product showed 32.2% and 30.4% identity to those of the pat and bar genes of the bialaphos (Bp) producers Streptomyces viridochromogenes and Streptomyces hygroscopicus, respectively; these genes encode phosphinothricin (PPT) N-acetyltransferases that function as enzymes in the Bp biosynthetic pathway and as resistance determinants. The S. coelicolor bar gene conferred high-level resistance to Bp when cloned in S. coelicolor on a high-copy-number vector. Enzymic assay showed that the S. coelicolor bar gene product inactivates PPT by transfer of acetyl groups from acetyl CoA. The S. coelicolor bar gene appears to be expressed from two promoters (p1 and p2) and is divergently transcribed with respect to hrdD. The downstream (barp2) transcript overlaps the hrdDp1 transcript and the upstream (barp1) transcript overlaps both the hrdDp1 and hrdDp2 transcripts. Inactivation of hrdD did not prevent transcription from either bar promoter, indicating that sigma hrdD is not essential for recognition of these sequences. PMID- 1916277 TI - Sequences of two adjacent genes, one (DAL2) encoding allantoicase and another (DCG1) sensitive to nitrogen-catabolite repression in Saccharomyces cerevisiae. AB - Reported are the nucleotide sequences of the yeast allantoicase-encoding gene (DAL2) and that of an unknown gene adjacent to it. Expression of the unidentified gene is sensitive to nitrogen catabolite repression (NCR) and regulated by the DAL80 product, a previously documented control element regulating allantoin pathway gene expression. Both genes possess multiple upstream activation sequences (UAS) homologous to the UASNTR element shown to be required for sensitivity to NCR. Also present upstream from DAL2 is a mutant form of the upstream induction sequence required for response of DAL7 to induction. Its occurrence in mutant form is consistent with the poor induction of DAL2 expression observed in vivo. PMID- 1916278 TI - The cell-cycle-regulated budding yeast gene DBF2, encoding a putative protein kinase, has a homologue that is not under cell-cycle control. AB - The budding yeast cell-cycle gene, DBF2, encoding a putative protein kinase, was shown to have a homologue, designated DBF20. This gene was cloned, sequenced, and confirmed to be highly homologous to DBF2, with over 80% identity in the 490 most C-terminal amino acid residues. Either gene could be deleted by itself, but deletion of both genes simultaneously was lethal, indicating that they are redundant for at least one vital function in yeast. In contrast to the DBF2 mRNA, which is expressed under cell-cycle control at or near START [Johnston et al., Mol. Cell. Biol. 10 (1990) 1358-1366], the DBF20 mRNA is expressed at a low level and not under cell-cycle control. Assuming there is no translational control, the differential expression of the mRNAs would result in a cell-cycle fluctuation of the relative levels of the gene products, which may constitute a novel form of regulation. PMID- 1916280 TI - DNA synthesis on discontinuous templates by DNA polymerase I of Escherichia coli. AB - DNA polymerases normally catalyze DNA synthesis in a template-directed manner. Generally, the continuity of the phosphodiester backbone of the template strand was thought to be an absolute requirement for DNA synthesis. Here, I demonstrate that a 3'-exonuclease-deficient derivative of the Klenow (large) fragment of Escherichia coli DNA polymerase I (PolIk) can carry out DNA synthesis on discontinuous templates in vitro. Addition of multiple nucleotides (nt) to the 3' end of a blunt-end duplex, templated by unlinked single-stranded oligodeoxyribonucleotides (oligos), was monitored electrophoretically. The reaction was demonstrable with either homopolymers or mixed-sequence oligos, but showed a requirement for complementarity between the first nt added to the duplex and the 3' nt of the unlinked oligo. These results demonstrate that continuity of the phosphodiester backbone of the template strand is not absolutely required for in vitro DNA synthesis by a 3'-exonuclease-deficient form of PolIk. PMID- 1916279 TI - Resolution of sequencing ambiguities: a universal FokI adapter permits Maxam Gilbert re-sequencing of single-stranded phagemid DNA. AB - We propose a method to resolve ambiguities encountered when single-stranded (ss) phagemid DNA templates are sequenced by the dideoxy method. A single oligodeoxyribonucleotide (oligo) is synthesized with the following features: (i) the 20 nucleotides (nt) at the 5'-end form a double-stranded hairpin containing a FokI restriction site, exactly as previously described by Podhajska and Szybalski [Gene 40 (1985) 175-182]; (ii) the 23 nt at the 3'-end hybridize to the (+)strand of ss phagemid DNA in the region complementary to the M13 universal sequencing primer. In a simple one-tube set of reactions, ss phagemid DNA is annealed to this oligo, cleaved by FokI at a unique site outside the vector multiple cloning site and then labelled at this unique site by Klenow polymerase and [alpha 32P]dCTP. These reactions provide a convenient route by which Maxam-Gilbert chemical degradation sequencing methods can be used to resolve ambiguities encountered in the dideoxy-sequencing of a unidirectional deletion series already prepared in popular phagemid vectors. A single oligo allows labelling of all members of a deletion series. A second universal oligo allows the same set of reactions to be applied to inserts cloned into (-)strand phagemids. PMID- 1916281 TI - Sequence and conservation of genes at the distal end of the transfer region on plasmids F and R6-5. AB - The nucleotide sequence of the region downstream of transfer gene traI, including fertility inhibition gene finO, on the conjugative plasmids F and R6-5, has been determined. Analysis of the F sequence revealed two open reading frames (ORF's), ORF248 and ORF186; ORF186 (finO) is interrupted by the insertion of IS3. The R6-5 sequence also contained ORF248 and an intact ORF186, although an additional ORF (ORF286) was located between the two genes. ORF248, which we have designated traX, and ORF186 (finO) are highly conserved on both plasmids. The organisation of these genes indicates that traI and traX on F, and traI, traX and ORF286 on R6 5 are co-transcribed from their respective promoters upstream of traI. Sequences homologous to traX were detected on a range of conjugative F-like plasmids, whereas sequences homologous to ORF286 were only found on plasmids R6-5, R100 and R1. The conservation of traX sequences suggests a functional importance for that gene and/or its product. PMID- 1916282 TI - Location and sequence of the todF gene encoding 2-hydroxy-6-oxohepta-2,4-dienoate hydrolase in Pseudomonas putida F1. AB - The gene (todF) encoding 2-hydroxy-6-oxohepta-2,4-dienoate hydrolase in Pseudomonas putida F1 was shown to be located upstream of the todC1C2BADE genes. The latter form part of the tod operon and encode the enzymes responsible for the initial reactions in toluene degradation. The nucleotide (nt) sequence of todF was determined and the deduced amino acid (aa) sequence revealed that the hydrolase contains 276 aa with a Mr of 30,753. The deduced aa sequence was 63.5% homologous to that reported for 2-hydroxymuconic semialdehyde hydrolase which is involved in phenol degradation by Pseudomonas CF600. PMID- 1916283 TI - Agrobacterium rhizogenes lacZ-rolC gene expression in Escherichia coli: detection of the product in transgenic plants using RolC-specific antibodies. AB - The rolC sequence of the Agrobacterium rhizogenes Ri plasmid was fused in-frame to the 3' end of the lacZ gene in plasmid pEX3. The fusion protein RolC-beta galactosidase was accumulated as insoluble inclusion bodies in Escherichia coli. Antibodies were raised in rabbits against the fusion protein. After affinity purification, RolC-specific antibodies were found to react with a 22-kDa polypeptide prepared from roots of transgenic tobacco plants possessing a rolC gene. The result of differential centrifugation suggested that RolC is present in the soluble fraction of transformed cells. PMID- 1916284 TI - New shuttle vectors for direct cloning in Saccharomyces cerevisiae. AB - We have constructed new shuttle vectors to facilitate the screening of recombinant plasmids after direct transformation of yeast cells. The vectors are pBluescript-based shuttle vectors in which the lacZ marker has been replaced by an analogous system based on the Saccharomyces cerevisiae URA3 gene. DNA fragments are inserted in a polylinker located after the beginning of the URA3 coding sequence. Transformants are selected either by Trp or Leu prototrophy. Plasmids bearing an insert are selected by growth on 5-fluoro-orotic acid (5 FOA), a uracil analog toxic to cells containing a functional URA3+ gene (thus, this method requires the recipient strain to be ura3-); only cells containing a plasmid with an insert that disrupts the functional continuity of the URA3 gene can grow on medium containing 5-FOA. Using these plasmids, we were able to directly reclone the ACE1 gene from genomic DNA by directly transforming a strain deleted for ACE1. These vectors can be used for a variety of purposes including rapid cloning of genes by complementation or expression of fusion genes driven from the URA3 promoter. PMID- 1916285 TI - Cloning and chromosomal mapping of nuclear genes encoding chloroplast and cytosolic glyceraldehyde-3-phosphate-dehydrogenase from Arabidopsis thaliana. AB - Both cDNA and genomic clones for the nuclear genes encoding chloroplast (cp) (gapA and gapB) and cytosolic (gapC) glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Arabidopsis thaliana have been isolated and characterized. Genomic Southern-blot analyses indicate that there is only one copy of each gapA, gapB and gapC gene in A. thaliana. Comparison of the deduced amino acid (aa) sequences shows that the A and B subunits are highly similar (80% positional aa identity), while there is less similarity between the cp and cytosolic subunits (45% aa identity). These relationships are consistent with the idea that the cp and cytosolic GAPDHs evolved from different lineages, as suggested in our previous study of tobacco GAPDHs [Shih et al., Cell 47 (1986) 73-80]. In addition, the chromosomal locations for the three gap genes were determined by restriction fragment length polymorphism mapping; the three gap genes are not closely linked, gapA (55.8 cM) and gapC (0.0 cM) are on chromosome 3, and gapB (51.3 cM) is on chromosome 1. PMID- 1916286 TI - A bioluminescence assay for gene expression by continuously growing mammalian cells: application for detection of human immunodeficiency virus type 1 (HIV-1). AB - An in-situ assay for monitoring regulated gene expression in continuously growing mammalian cells is described. This technique can be used for the detection of the transactivator (Tat) protein in human immunodeficiency virus(HIV)-infected cells. Human kidney cells 293, harboring the luc gene, and fused to the HIV-1 long terminal repeat, were isolated and served as tester cells. Tat is supplied by transfection with a tat-carrying plasmid, or alternatively by addition of Tat containing cell extracts, made from virus-infected or plasmid-transfected cells. Light emitted from the tester cells is recorded on film continuously, or by a photo sensor. Transactivation by HIV Tat results in a pronounced increase in light emission from the tester cells (up to 3000-fold). This assay, which detects HIV-specific gene products, may be used as a diagnostic tool for the detection of active HIV present in peripheral blood. PMID- 1916287 TI - A surface expression vector for antibody screening. AB - To select specific antibodies (Ab) from large recombinant libraries using small amounts of antigen, we have constructed a phagemid that expresses a single-chain Ab fused to pIII, a coliphage protein product of gene III that initiates infection by binding to F pili. Surprisingly, the production of the fusion protein (Ab::pIII) was induced by wild-type (wt) phage fd in the absence of IPTG. Ab::pIII was identified by a monoclonal Ab to an epitope in the linker sequence between the heavy and light chains, and by antisera to their N-terminal sequences. It is able to bind antigen and be assembled into infectious phagemid particles that can be enriched on columns of immobilised antigen. The phagemid DNA is even smaller than that of wt fd phages and can easily be propagated in plasmid form. Most importantly, its Ab::pIII-encoding gene can be tightly repressed so that Ab libraries can be amplified without risk of being dominated by deletion mutants. After induction, however, large quantities of the fusion protein can be produced, thus greatly facilitating its analysis. PMID- 1916288 TI - The salmon gene encoding apolipoprotein A-I: cDNA sequence, tissue expression and evolution. AB - A cDNA encoding an apolipoprotein (Apo) has been isolated from the Atlantic salmon (Salmo salar) and sequenced. It encodes a peptide of 258 amino acids (aa), including a signal peptide of 18 aa, with 5'- and 3'-untranslated regions of the mRNA of 12 and 329 nucleotides, respectively. The protein has structural features in common with other Apo's of human and avian origin, including conserved sequences in the signal peptide and a series of internal repeats of 22 aa. The sequence has been identified as salmon Apo A-I (sApoA-I), and has 23% aa identity with human ApoA-I. Northern-blot analysis using the sApoA-I cDNA probe against total RNA prepared from several salmon tissues detects the expression of this gene in liver, intestine and muscle. A phylogenetic analysis reveals that the mammalian ApoA-I, ApoA-IV and Apo-E aa sequences are more closely related to each other than any of them are to sApoA-I. This suggests that the duplication events, from which A-I, A-IV and E arose, occurred after the divergence of the tetrapod and teleost ancestors. PMID- 1916289 TI - Isolation, characterization and sequencing of the chicken apolipoprotein-AI encoding gene. AB - The chicken ApoAI gene has been isolated and characterized. This gene contains three introns: the first is situated after nucleotide (nt) 41 in the 5' untranslated region of the gene, the second interrupts the codon specifying the Gly-10 of the prepeptide, and the third disrupts the codon for Asp42 in the mature ApoAI protein. The chicken ApoAI gene has 62.6% sequence similarity with the human and 65.0% similarity with the rat gene. Intron-exon organization of the chicken gene is similar to that of human and rat ApoAI genes. Two different transcriptional start points (tsp), only 2 nt apart from each other, have been obtained for the chicken ApoAI gene. The 5'-flanking sequence of the gene contains TAAATA (TATA-like box) and CCACAT (CCAAT-like box) sequences, which are located 21 bp and 96 bp upstream from the tsp, respectively. This gene's sequence and structural organization provide a basis for future studies of the regulation of chicken ApoAI gene expression. PMID- 1916290 TI - Cloning and expression analysis of a cDNA encoding fumarylacetoacetate hydrolase: post-transcriptional modulation in rat liver and kidney. AB - Fumarylacetoacetate hydrolase (FAH) is an enzyme which is deficient in human hereditary tyrosinemia type 1. We have cloned and sequenced a rat liver cDNA encoding FAH. The identity of the clone was ascertained by hybrid-selection experiments and deduced amino acid (aa) sequence homologies with sequenced oligopeptide fragments of the purified rat liver protein. The cDNA codes for a 419-aa protein of 45,946 daltons. We used this cDNA as a probe in conjunction with a specific anti-rat FAH antibody to study the expression pattern of the FAH gene in rat liver and kidney. Northern blot analysis indicates that the kidney contains slightly more FAH mRNA that the liver. Western blotting shows, however, that the liver contains about twice as much FAH protein as the kidney. Primer extension experiments suggest that there are no differences in the 5' untranslated (UT) ends of the FAH mRNA of both tissues. We conclude that synthesis of the FAH protein is in part regulated at the post-transcriptional level in rats liver and kidney, and that this regulation does not appear to be mediated by the 5'-UT sequence of the FAH mRNA. PMID- 1916292 TI - Sequence and expression of the MnP4 gene encoding basic proline-rich protein in macaque salivary glands. AB - We report here the macaque MnP4 cDNA and genomic sequences which encode a basic proline-rich protein (PRP), which is synthesized in macaque parotid gland and submandibular gland. The locations of intron positions and the prototype of the tandem 20-amino-acid repeat motif with the sequence, PPPPGKPQGPPQQGGNKPQG, in MnP4, were compared to those in related genes encoding PRP and glutamic/glutamine rich proteins (GRP) in humans and rodents. Exceedingly high homology of the first exon and 40-bp region immediately upstream of exon I is observed with other PRP genes of all species studied. In order to identify the regulatory elements involved in control of MnP4 gene expression, a rat submandibular gland-derived cell line (RSMT-A5) was transfected with MnP4-cat constructs that contained the promoter and 5'-flanking regions of the macaque MnP4 gene fused to the bacterial cat gene. Deletion analysis revealed that putative positive and negative regulatory elements reside between nucleotides (nt) -107 and +5, and nt -586 and 108, respectively. As part of this study, the promoter of the macaque MnP4 gene appears to be salivary gland specific. This salivary gland-specific gene expression attests to the complexity of transcriptional regulation in eukaryotes. PMID- 1916291 TI - The ornithine aminotransferase-encoding gene family of rat: cloning, characterization, and evolutionary relationships between a single expressed gene and three pseudogenes. AB - As a first step towards understanding the molecular mechanisms through which the expression of the gene (OAT) encoding ornithine aminotransferase (OAT) is regulated in a tissue-specific manner, we have used a near full length OAT cDNA to isolate related sequences from a rat genomic DNA library. Twenty-one unique clones representing five contigs and spanning approximately 140 kb of genomic DNA were isolated and characterized. From these clones we have identified a single expressed OAT gene and three processed pseudogenes. The comparison of the EcoRI, BamHI, and HindIII fragments contained within these genomic clones with those detected in total genomic DNA by the cDNA probe suggests that essentially all of the OAT-related sequences in the rat genome have been isolated. Thus, the tissue specific regulation of OAT gene expression appears to be effected through a single expressed gene. Data are presented which suggest that the OAT-1, OAT-2, and OAT-3 pseudogenes arose approximately 28.5, 7.3, and 25.1 Myr ago, respectively. Mutation rates are presented for each codon position of the expressed rat and human OAT genes. The region of the rat genome flanking the boundary of the OAT-3 pseudogene is of additional interest as it shares considerable identity to sequences contained within expressed genes and flanking other processed pseudogenes. PMID- 1916293 TI - Internal deletions in human interleukin-6: structure-function analysis. AB - By cDNA mutagenesis, we have constructed internal and C-terminal deletions (delta 21-51, delta 52-97, delta 97-104, delta 127-174, delta 97-184 and delta 134-184) in human interleukin-6 (hIL-6). All those deletion-carrying hIL-6 (delta hIL-6) proteins were then produced in Xenopus laevis oocytes and examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results show that, at least in frog oocytes, the first potential N-glycosylation site (Asn45) is utilized exclusively. The IL-6 conformation of these deletion-carrying proteins has been studied by immunoprecipitation with two kinds of monoclonal antibodies (mAb's): mAb's that show preference towards denatured hIL-6, or conformation-specific mAb's. The binding pattern of these two series of mAb's indicated that the IL-6 conformation has been largely destroyed for four of our delta-proteins. Proteins delta 21-51 and delta 127-174 have kept a part of the IL 6 tertiary structure since they are still recognized by some conformation specific mAb's. All of these delta hIL-6 proteins were inactive in the IL-6 hybridoma growth factor (HGF) assay and unable to inhibit the HGF activity of the recombinant human wild-type IL-6 (wt hIL-6). Moreover, the oocyte-synthesized delta hIL-6 (delta 21-51, delta 127-174, delta 97-184, delta 134-184) did not bind to the IL-6 receptor. Finally, we have produced two proteins with aa 29-33 or 97-104 substituted by corresponding murine IL-6 (mIL-6) sequences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916294 TI - Cleavage pattern of the homing endonuclease encoded by the fifth intron in the chloroplast large subunit rRNA-encoding gene of Chlamydomonas eugametos. AB - The fifth group-I intron in the chloroplast large subunit rRNA-encoding gene of Chlamydomonas eugametos (CeLSU.5) is mobile during interspecific crosses between C. eugametos and Chlamydomonas moewusii. Like the six other mobile introns that have been well characterized so far, CeLSU.5 contains a long open reading frame (ceuIR) coding for a site-specific endonuclease (I-CeuI) that cleaves the C. moewusii intronless gene in the vicinity of the intron-insertion site. This stimulates gap repair and mediates efficient transfer of the intron at its cognate site. By expressing the ceuIR gene in the Escherichia coli vectors pKK233 2 and pTRC-99A, we recently demonstrated that the endonuclease is highly toxic to E. coli [Gauthier et al., Curr. Genet. 19 (1991) 43-47]. To eliminate this problem and characterize the cleavage pattern and recognition sequence of the I CeuI endonuclease, we have expressed the ceuIR gene in E. coli under the control of a bacteriophage T7 promoter in a tightly regulated M13 system, and developed an in vitro system to assay partially purified I-CeuI activity. This allowed us to determine that I-CeuI recognizes a sequence of less than 26 bp centered around the insertion site and produces a staggered cut 5 bp downstream from this site, yielding 4-nucleotide (CTAA), 3'-OH overhangs. PMID- 1916295 TI - Geminivirus-based shuttle vectors capable of replication in Escherichia coli and monocotyledonous plant cells. AB - Shuttle vectors have been constructed that are able to replicate in either Escherichia coli or plant cells. They contain the ColE1 origin of replication and parts of the wheat dwarf virus genome, a geminivirus infecting a variety of species of monocotyledonous plants. Such plasmids are able to replicate in E. coli and wheat cells. The plasmids can be rescued in E. coli and show no changes during their passage through plant cells. Such an E. coli/plant cell shuttle vector system could be used for the amplification of foreign genes in plant cells, for studies on DNA rearrangement or the isolation of plant transposons. PMID- 1916296 TI - Murine gamma E-crystallin is distinct from murine gamma 2-crystallin. AB - The murine gamma E-crystallin-encoding gene (gamma E-cry) was isolated from a genomic DNA library. The nucleotide (nt) sequence was determined of 1100 bp upstream from the first exon to the polyadenylation site, comprising more than 3600 bp. The gene was characterized by phylogenetic nt sequence analysis in context with the already described gamma-cry genes from rat, mouse and human. The gamma E-cry genes (mouse and rat) are clearly separate from the corresponding gamma F-cry genes. Based on the phylogeny, the discussion about the murine gamma 2-cry classification as gamma F-cry [Bloemendal et al., Exp. Eye Res. 48 (1989) 465-466] is resolved. The murine gamma E-cry gene has characteristics similar to other genes from the gamma-cry gene family, except for an 18-fold repeat of the sequence, 5'-CTCAG, located at the 3'-end of intron B. There is no similar repeat structure in any other gamma-cry gene. No binding site for a common transcription factor could be detected among the 1100 bp of the 5'-region. PMID- 1916297 TI - Production of functional rat HMG1 protein in Escherichia coli. AB - High-mobility group-1 protein (HMG1) was produced in Escherichia coli under the control of the T7 promoter/T7 RNA polymerase system. The protein can be produced and purified with yields similar to those obtained from animal tissues. HMG1 purified from E. coli is homogeneous and capable of selectively binding cruciform DNA, indicating that post-translational processing of vertebrate HMG1 is not necessary for its DNA-binding ability. PMID- 1916298 TI - Characterization of Alu repeats surrounding the human ferredoxin-encoding gene. AB - Three Alu sequences have been identified surrounding the human ferredoxin encoding genes. Among them, one is located about 1000 bp upstream from the active gene, whereas two others flank the ferredoxin pseudogene, psi FDX3. All these Alu sequences contain poly(A) tails and are flanked by direct repeats, indicating that they arose by RNA-mediated transposition events. PMID- 1916299 TI - The poverty of living alone. PMID- 1916301 TI - Laboratory testing: current recommendations for older adults. AB - Efficient use of laboratory testing is essential in the care of the elderly, both for making accurate diagnoses and keeping costs in line. Further, primary care physicians treating the elderly need to have an understanding of the effect of age on laboratory values. Clinically significant change occurs with age in some values but not in others. This review focuses first on the effect of aging on different laboratory values and then discusses current recommendations for the most commonly used laboratory tests. PMID- 1916300 TI - Managing hypertensive emergencies and urgencies in the geriatric patient. AB - The aging cardiovascular and renal systems put the elderly patient at increased risk of end-organ damage from marked hypertension. Thus, the office-based physician needs to be skilled in making the diagnosis of a hypertensive urgency or emergency based on accurate blood pressure readings and an assessment of the heart, brain, retina, and kidney. Hypertension urgency and emergency are distinguished from each other by the clinical decision of how quickly the blood pressure must be lowered. The clinician has a wide variety of agents from which to choose for pharmacologic treatment, with the goal being a smooth and safe reduction in blood pressure. PMID- 1916302 TI - Topical steroids: a guide for use in the elderly patient. AB - Topical steroids are indicated for the treatment of a number of skin disorders affecting the elderly, including several forms of dermatitis and psoriasis. Proper selection of a topical steroid is based on several factors, including the disorder and anatomical site being treated, the potency, dosage form, and application technique of the steroid, potential side effects, and the presence of coexisting factors such as infection and preexisting atrophy. This review outlines guidelines for the safe, efficacious selection and administration of these commonly prescribed agents in the elderly patient. PMID- 1916303 TI - Ophthalmic herpes zoster: diagnosis and antiviral therapy. AB - Elderly patients, whether of normal or depressed immune status, are at increased risk of herpes zoster infection. Ocular complications occur in 50% of patients with zoster that reactivates in the ophthalmic division of the trigeminal ganglion. Early intervention with high-dose oral acyclovir has been effective in preventing many of these complications, while reducing the duration of the acute infection. Postherpetic neuralgia remains a difficult therapeutic problem, and options are offered. PMID- 1916304 TI - Geriatric depression: atypical presentations, hidden meanings. AB - Geriatric patients with affective illness often present with unusual or atypical symptom patterns that make diagnosis difficult. Depression may be masked as pseudodementia, somatization, or anxiety/irritability, or it may be an underlying factor in pain syndromes and alcohol abuse. In the elderly, depression may be a primary or secondary symptom of a concomitant medical condition, including thyroid disease and occult neoplasm. Common medications, including some antihypertensive agents, may also have etiologic significance. PMID- 1916305 TI - Here's to happier endings. PMID- 1916306 TI - Caring for older women: no more 'hand-me-down' medicine. PMID- 1916307 TI - Age-related changes of supranucleosomal structures and DNA-synthesizing properties of rat liver chromatin. AB - The template activity, nucleosomal pattern and thermodenaturation parameters of transcriptionally low active (TLA) and transcriptionally active liver chromatin fractions were studied in adult (6-8 months) and old (26-28 months) rats. The following age-related changes of chromatin template properties were found: decrease of endogenous DNA polymerase alpha- and beta-activity in vitro in both chromatin fractions, and redistribution of newly synthetized RNA between mono- and oligonucleosomes in the TLA fraction. These changes are thought to be connected with age-related reorganization of chromatin structure, i.e. with increase of DNA-protein interactions, which stabilize association of chromatin supranucleosomal structures. PMID- 1916308 TI - Habituation of the proboscis extension response as a function of age in Drosophila melanogaster. AB - Habituation of the proboscis extension response induced by sugar tarsal stimulation was individually studied in males of Drosophila melanogaster all along the adult life span (2-71 days of age at 25 degrees C). A polynomial regression fits the best the results: the speed of acquisition of this kind of learning decreases between the ages of 3 and 35 days, a plateau being observed in flies older than 35 days. Similar results have been previously obtained using associative learning tasks of increasing complexity. These effects of age could be due to a memory impairment, but also to deficits in the process of central inhibition of irrelevant motor responses. PMID- 1916309 TI - Repair of DNA single-strand breaks in lymphocytes from Alzheimer's disease patients. AB - We have studied DNA single-strand breaks (SSB) and their repair, after gamma irradiation, in lymphocytes from patients with Alzheimer's disease (AD) and from normal, age-matched individuals, using alkaline sucrose gradient centrifugation. We have found that values for AD patients and normals are similar in each of the following: level of breaks in unirradiated cells, level in cells irradiated with 150 Gy and rate of repair. Also, preliminary results for young and old normal individuals showed no significant difference between their SSB levels in unirradiated cells, nor between levels in irradiated cells nor in repair rate. In all cases, post-irradiation repair appeared to be almost complete after 50 min incubation. We conclude that gamma-irradiation produces no gross difference in the initial number of SSB between lymphocytes from AD patients, old normals and young normals, and that their repair is equally proficient. PMID- 1916310 TI - Effects of age and turpentine-induced inflammation on the activity of ceruloplasmin from blood of CFY rats. AB - The activity of ceruloplasmin (CP) increased 3-fold in rat blood between 1 week and 20 months of age, but the difference in CP activity of adult and old rats was only 14%, which still is statistically significant (p less than 0.01). The increase in NaCl and KCl concentrations in vitro resulted in the same exponential decrease in activities of CP from both young and old animals. Turpentine-induced inflammation caused an increase in blood CP levels in both young (52%) and old (25%) animals compared to age-matched controls (p less than 0.001 and p less than 0.01, respectively). These results indicate that the antioxidant activity of CP is maintained as a function of age in rat blood, which is beneficial for preventing the increase in lipid peroxidation. PMID- 1916311 TI - The immune-neuroendocrine homeostatic network and aging. AB - A unified model of immune and neuroendocrine aging is proposed. In doing so, the idea of an immune-neuroendocrine homeostatic network in higher animals is introduced. Next the concepts of homeorrhesis (moving homeostasis), developmental program and their relation to systemic aging are discussed. Finally, the experimental evidence supporting the view that immune and neuroendocrine aging are interdependent processes is briefly reviewed. This evidence makes it clear that organismal aging can no longer be described in terms of purely neuroendocrine or immunologic models. It is hoped that the idea of an immune neuroendocrine homeostatic network will provide a conceptual frame of reference where the growing body of experimental data regarding immune-neuroendocrine interactions during aging can be naturally accommodated. PMID- 1916313 TI - Dark adaptation and falls in the elderly. AB - The human eye is capable of adjusting to wide variations in light intensity by altering the pupil size and the sensitivity of the retina to light. Falls are one of the commonest problems of old age, and the causes are multifactorial. As falls often occur at night, this study was designed to compare dark adaptation in groups of elderly fallers and non-fallers. Twenty-two female patients in a geriatric assessment ward were included in the study and classified as 'fallers' or 'non-fallers'. A full ophthalmic examination was performed on each subject, and dark adaptation measured, in a single-blind fashion, using the Friedmann visual field analyser; following initial bleaching of the retinal photoreceptors, the room was placed in total darkness and retinal sensitivity measured every minute for 20 min. The values, expressed as log filter density, were plotted against duration of time in the dark. The mean values at 5 min were 0.9 in the fallers and 1.4 in the non-fallers (p less than 0.02 unpaired t test) and at 20 min 2.2 and 3.2, respectively (p less than 0.04). These results indicate reduced retinal sensitivity and hence impaired dark adaptation in the falling group. Lighting levels in the homes of many old people have been shown to be inadequate. Impaired dark adaptation may leave an elder person virtually blind for a minute or more on moving from a bright room to a darker area. The provision of night lights in the homes of recurrent fallers may offset the influence of impaired dark adaptation. PMID- 1916312 TI - Body composition in hypertensive elderly and middle-aged patients. AB - The occurrence of hypertension, leading to various life-threatening complications in the elderly is a widely recognized problem. The changes of body composition were determined in 120 control and untreated hypertensive subjects of various ages. In middle-aged hypertensive males, the total blood volume and plasma volume increased significantly compared to those of the healthy controls, while this increase was not significant in the case of hypertensive middle-aged females. In contrast, in the elderly hypertensive male subjects, the volume of all fluid components decreased, except the total body fat and the vascular volumes. There was a slight, statistically non-significant, increase in all the vascular volumes except in the red cell mass. The elderly hypertensive females showed the same tendency compared to the healthy controls of the same age. The vascular compartments seem to be decreased in elderly males, compared to those of the middle-aged males, while slightly increased in elderly females. PMID- 1916314 TI - Core body temperature in the elderly and factors which influence its measurement. AB - Several studies have reported that core body temperature decreases with age and has greater variability in older populations. Furthermore, oral measurement, the most frequently used clinical method for determining fever, may not accurately reflect core body temperature. This study was designed to compare accurate measurements of oral and core body temperatures in a group of 93 healthy subjects, aged 62-96, under controlled conditions. Increasing age, presence of dentures, and type of thermometer were examined to determine if they affect body temperature measurements. Core temperatures did not show a negative relationship with advancing age (r = -0.02) nor did variation in temperatures increase with age. Neither the type of thermometer nor the presence of dentures significantly affected the measurement of temperature. PMID- 1916315 TI - Long-term treatment effects in patients with bilateral retinoblastoma: ocular and mid-facial findings. AB - A total of 99 patients with bilateral retinoblastoma who had been treated between 1965 and 1982 were reexamined in April 1988 to study the late effects of treatment. Their median age at the follow-up visit in 1988 was 16 years (range, 6 27 years), and the median follow-up was 15 years (range, 6-26 years). All patients underwent a full eye examination, morphometric measurements of the mid face and genetic counselling. Each eye or orbit and the corresponding side of the patient's mid-face were evaluated separately, resulting in 198 data sets from 99 individuals. Subjects were divided into four treatment groups according to whether photo- and cryo-coagulation, enucleation, radiation therapy or various combinations thereof were used. In all, 81 eyes had a visual acuity of greater than 0.4 (in 23 of these, however, only with low-vision aids). Within a dose range of 36-51 Gy, the location of the tumor (36%) or cataract (15%) were the main factors responsible for poor visual acuity, whereas radiation retinopathy and/or optic neuropathy occurred in only three cases. Cataracts were more frequently observed following orthovoltage as compared with megavoltage therapy (P = 0.012). A total of 72 eyes had been enucleated and had not received radiation therapy at any time. Cosmetic results (as measured by several parameters) in these cases were significantly better then those in 28 subjects who underwent combined radiation therapy and enucleation. As defined by various subjective as well as objective findings, mid-facial hypoplasia occurred significantly more often following orthovoltage as compared with megavoltage therapy. PMID- 1916317 TI - Nasal retinal dragging in X-linked retinoschisis. AB - X-linked retinoschisis is a disorder characterized by the presence of foveal schisis and often peripheral splitting of the retina in the nerve fiber layer. The accompanying complications include vitreous hemorrhage and retinal detachment, which can lead to blindness. In this report five patients who presented during infancy or early childhood had nasal retinal dragging. PMID- 1916316 TI - Diabetic retinopathy after successful kidney-pancreas allotransplantation: a survey of 18 patients. AB - To investigate the effects of normoglycaemia on diabetic retinopathy, we evaluated 18 uremic diabetic patients before and after successful pancreas kidney transplantation. In all, 12 uremic diabetic patients who submitted to kidney transplantation alone served as the control group; 4 of these subjects received a kidney transplantation alone, whereas 8 underwent a double kidney-pancreas transplantation but lost the pancreas graft within the first few weeks post surgery. The mean age and the mean duration of both diabetes and dialysis were comparable in the two groups. All patients were studied prior to and at 6 and 9 months after surgery, then at annual intervals. Subjects were divided into three groups according to follow-up: less than 1 year, between 1 and 3 years and greater than 3 years. At each control visit, a complete clinical examination was performed by two independent examinators; retinal fluorescein angiography was carried out as well. The following parameters were evaluated: visual acuity, capillary closure, macular oedema, neovascularization at the disk and elsewhere and vitreous haemorrhage. A score ranging from -2 to +2 was assigned to each parameter for quantification of the variation between baseline values and those obtained at the end of the follow-up. This score was assigned by two different ophthalmologists. Eyes that were affected at baseline by end-stage diabetic retinopathy (secondary retinal detachment, neovascular glaucoma) were not entered in the study. A total of 18 eyes were lost to follow-up in the 2 groups because of laser treatment, cataract extraction, anterior ischaemic optic neuropathy and cytomegalovirus retinitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916318 TI - Reduction of severe macular edema in eyes with poor vision after panretinal photocoagulation for proliferative diabetic retinopathy. AB - Currently available data from multicenter randomized trials on laser treatment of diabetic macular edema refer only to eyes with pretreatment visual acuities of 20/160 or better. After observing reduction of more severe macular edema and visual improvement following panretinal photocoagulation (PRP) alone in some patients, we reviewed our experience with this problem. In 18 eyes of 14 patients with proliferative diabetic retinopathy and visual acuity of 20/200 or worse, secondary to severe macular edema were identified. At 6 months after PRP without focal macular laser treatment, macular edema was reduced in 13 eyes, 8 of which improved by greater than or equal to 2 lines of vision. Among the latter 8 eyes, the visual acuity of 4 recovered to 20/80 or better; the remaining 10 eyes, which had chronic retinal pigment epithelial atrophy or extensive macular ischemia, did not improve. Based on these observations, we suggest that peripheral PRP performed in multiple sessions over several months may have a beneficial effect on severe macular edema in some eyes with adequate macular perfusion. PMID- 1916319 TI - Detection and quantification of hyperfluorescent leakage by computer analysis of fundus fluorescein angiograms. AB - Digital imaging systems can be used for direct acquisition of images of the ocular fundus or for their indirect acquisition from fundus photographs or transparencies. Computerised image processing techniques can then be used to manipulate and quantify features of interest. We describe a method for the detection and quantification of macular leakage in fluorescein angiograms. The rate of change in fluorescence over time is examined on a pixel-by-pixel basis and used to provide a gradient threshold that discriminates pixels displaying leakage from normal pixels. A region-growing technique is then used to enhance the detection of leakage missed by gradient thresholding alone. This report discusses the potential applications of the technique and highlights the methodology required to obtain reproducible results. PMID- 1916320 TI - Retinal blood flow in diabetic children and adolescents. AB - A total of 209 diabetic children and adolescents aged 6-17 years (mean, 12.6 +/- 2.3 years) were examined by ophthalmoscopy, video fluorescein angiography and hemoglobin (HbA1c) test. Microaneurysms were found in 26% of the children (ophthalmoscopy, 11%; angiography, 23%). The prevalence of retinopathy was 16% in patients aged 6-10 years, 27% in those aged 11-13 years and 36% in those aged 14 17 years. Only five diabetics aged 11-17 years showed lesions other than microaneurysms (hard exudates, intraretinal hemorrhages or retinal capillar leakage). Retinal blood flow was quantified using video fluorescein angiography. The arm-retina time (ART) and the arteriovenous passage time (AVP) as parameters of the retinal microcirculation were obtained using an image analysing system. The mean value for ART was 9.7 +/- 2.5 s and that for AVP was 1.43 +/- 0.52 s. AVP was significantly shorter in diabetic children and adolescents with good glycemic control (HbA1c, less than 7%; AVP, 1.35 +/- 0.44 s) than in those with bad glycemic control (HbA1c, greater than or equal to 9%; AVP, 1.65 +/- 0.51 s). PMID- 1916321 TI - Factors influencing the ocular pulse--axial length. AB - The amplitude of the intraocular pressure pulse and pulsatile ocular blood flow (POBF) were correlated with the axial length and refraction of 68 eyes of healthy subjects. Measurements were obtained with subjects in the sitting position using an ophthalmic A-scan and a pneumotonometer linked to a Langham ocular blood-flow system. The amplitude of the ocular pulse and the magnitude of POBF were found to decrease with increasing axial length (r = -0.61, P less than 0.001 and r = 0.74, P less than 0.001, respectively). A similar close relationship was found between the ocular pulse amplitude and POBF and the refractive state of the eye (r = 0.63, P less than 0.001 and r = 0.7, P less than 0.001, respectively). The reasons for the association are discussed and the importance of the observations in the construction of studies in which ocular pulse amplitude or POBF are to be measured in different groups of subjects is emphasised. PMID- 1916322 TI - Effects of artificial tears on corneal epithelial permeability in dry eyes. AB - The aim of this study was to detect possible changes in the permeability of the corneal epithelium in dry eye patients treated with artificial tears. For this reason, corneal epithelial permeability was measured in 68 consecutive dry eye patients before and after 8 weeks of treatment with artificial tears by means of objective fluorophotometry (polyvinyl alcohol 1.4% + chlorobutanol 0.5%, 25 subjects; polyvinyl pyrrolidone 2% + benzalkonium chloride 0.005%, 25 subjects; polyvinyl pyrrolidone 2% without preservative, 18 subjects). Before treatment, the stromal fluorescein uptake of dry eyes was three times higher than that of healthy control eyes. Eight weeks after the beginning of treatment the corneal epithelial permeability of patients treated with polyvinyl alcohol 1.4% + chlorobutanol 0.5%, as well as of those treated with polyvinyl pyrrolidone 2% without preservative, was reduced significantly (-44.9% and -43.4%, respectively; P less than 0.001). However, patients who had been treated with polyvinyl pyrrolidone 2% + benzalkonium chloride 0.005% showed no significant change in corneal epithelial permeability after treatment (-7.9%; P = 0.3). PMID- 1916323 TI - Differential spectrofluorometry in the human vitreous: blood-retina barrier permeability to fluorescein and fluorescein glucuronide. AB - A method is described for the separate quantitation of fluorescein and fluorescein glucuronide in the vitreous by differential spectrofluorometry. An ocular fluorometer was equipped with monochromatic laser excitation at two rapidly interchangeable wavelengths. The data analysis accounts for absorption of light in the cornea, lens, and extrinsic ocular fluorophores. Examination of seven patients with insulin-dependent diabetes and different degrees of diabetic retinopathy demonstrated that both fluorescein and fluorescein glucuronide enter the eye through the blood-retina barrier. The mean ratio between the permeabilities of fluorescein glucuronide and fluorescein was 0.9 (range, 0.3 1.9). Thus, differences in the molecular size and lipid solubility of the two substances appear to be of little or no importance for their inward penetration of the barrier. No association was found between the relative permeability and the degree of retinopathy. PMID- 1916324 TI - Determination of spatial coordinates in ocular fluorometry. AB - A method has been developed for the determination of spatial coordinates of ocular fluorescence measurements made by a non-contact-lens type of fluorometer (Fluorotron, Coherent Inc., Palo Alto, Calif., USA). The method is based upon a mathematical model of the instrument and the eye. The model is adapted to the individual eye by the extraction of information from the fluorescence scan and the use of keratometry to determine the radius of curvature of the anterior corneal surface. The validity of the model was examined by comparison of the ocular axial length as measured by fluorometry vs ultrasonometry in 26 eyes of healthy human subjects. The results of fluorometry differed from those of ultrasonometry by less than +/- 2%. PMID- 1916325 TI - Lens fluorometry: light-attenuation effects and estimation of total lens transmittance. AB - Front-face fluorometry of the axial fluorescence profile of the lens is influenced by attenuation of light along the optical pathways leading to and from the detection volume. The resulting distortion is evident when the curve is compared with the intrinsic profile that can be recorded by direct measurement on the transected lens. Assuming that attenuation of light by scatter and absorption is proportional to fluorescence, the intrinsic profile can be reconstructed from the non-invasive fluorescence profile. The calculations involve the deduction of total lens transmittance and fluorescence-related absorptivity, parameters that provide essential information about the optical quality of the lens. The method was applied to human lens fluorometry in vivo and in vitro (excitation 430-490 nm, fluorescence 530-630 nm). Even the most anterior lens fluorescence measurements were found to be markedly affected by attenuation of light in the lens. Lens transmittance estimates agreed within +/- 12% with direct measurements of lens transmittance. The differences were due in part to inter-individual variations in the shape of the intrinsic fluorescence profile of the lens. PMID- 1916326 TI - Origin and renewal of the intrinsic glycoproteins of the aqueous humor. AB - Rabbits were injected either intravitreally or intra-aqueously with L-[3H]-fucose and killed at several intervals after the administration of this marker for glycoproteins. The aqueous humor, the vitreous body and the ciliary body were processed for radiometry (liquid scintillation counting), sodium dodecyl sulfate poly-acrylamide gel electrophoresis (SDS-PAGE) and fluorography. Light microscopic autoradiography was carried out on semi-thin sections of the ciliary body and revealed intense activity in terms of the synthesis, migration and renewal of glycoproteins in the ciliary epithelium. The amount of unbound [3H] fucose in the aqueous humor decreased sharply by 4 h, and the labeled glycoproteins were present only in very small quantities at 1 day after the intra aqueous injection. When [3H]-fucose was injected intravitreally, unbound radiolabel could be detected in the aqueous humor for greater than 1 day and the labeled glycoproteins, for up to 21 days after injection. The amount of unbound or bound [3H]-fucose was higher in the vitreous than in the aqueous at any interval after the intravitreal injection. Following the intra-aqueous injection, the amount of label that reached the vitreous body was practically insignificant. The levels of radioactivity in the serum were extremely low, as they were in the contralateral eye when tritiated fucose was injected into one eye only. Most of the Coomassie blue-stained bands detected in SDS-PAGE contained labeled glycoproteins as revealed by fluorography of gels simultaneously containing aqueous and vitreous samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916327 TI - The effect of wavelength on glial fibrillary acidic protein immunoreactivity in laser-induced lesions in rabbit retina. AB - Rabbit retinas were treated with low-intensity laser coagulation at five different wavelengths. Using an indirect immunocytochemical method, the retinas were stained for glial fibrillary acidic protein (GFAP) at 2, 4, 21 and 32 days after coagulation such that we could follow GFAP expression in the Muller cells during retinal repair. GFAP-positive staining was found in the end feet of the Muller cells at 2 days after laser coagulation. GFAP immunoreactivity was observed throughout the Muller cells, surrounding the central necrotic tissue, at days 4, 21 and 32 after laser coagulation. Scar tissue in the subretinal space at days 21 and 32, which was more pronounced for the longer wavelengths produced by the Krypton and Nd-YAG lasers, also showed GFAP immunoreactivity. The Muller cells remained GFAP-immunoreactive for at least 32 days after laser coagulation. PMID- 1916328 TI - A histopathologic study of retinal lesions inflicted by transscleral iontophoresis. AB - In the present study, retinal lesions were induced by transscleral iontophoresis (1.5 mA) in rabbits. The size and severity of the lesions increased with the duration of application (2-25 min). No lesion was noted after less than 1 min application. Immediately after 5 min iontophoresis, the edematous retina exhibited necrotic retinal pigment epithelium (RPE), loss of outer segments, and thinning of the inner and outer nuclear layers. At 5 days after iontophoresis, there was a proliferation of RPE cells and macrophages in the subretinal space, with thinning of the inner and outer retinal layers continuing. By day 14, the retina had been reduced to a glial membrane. Immediately after 15 min iontophoresis, the damaged retina appeared in a mummified form containing no cellular elements. By day 5 thereafter, macrophages and actively proliferating RPE cells had been noted in the necrotic retina. By day 14, a glial membrane had formed. PMID- 1916329 TI - Histology and transmission electron microscopy of the cornea in xeroderma pigmentosum type C. AB - Xeroderma pigmentosum is a very rare precancerous skin disease that is triggered by sunlight. It is caused by a defect in the DNA repair system and causes benign and malignant transformations. Only eye tissues that come into contact with UV light are affected, such as the lids, conjunctiva and cornea. We describe a patient who suffered from xeroderma pigmentosum type C, showing the typical skin alterations but no sign of malignancy. A perforating keratoplasty was performed on both eyes because of the dense opacity of the corneas. The corneal buttons obtained were examined by light and transmission electron microscopy. Degeneration was found only in the basal-cell layer of the corneal epithelium. The most severe morphological changes were seen in Bowman's layer, the subepithelial stroma, Descemet's membrane and the corneal epithelium. Bowman's layer was often interrupted or replaced by a degenerative pannus, which extended into the underlaying stroma. Subepithelial "channels" were localized in the basal epithelium and protruded into the subepithelial stroma. In both corneas, Descemet's membrane contained different amounts of so-called lattice collagen, and the remaining endothelial cells in the left cornea contained numerous melanin granules. PMID- 1916330 TI - [Hygienic evaluation of glue compositions for use in domestic drinking water supply installations]. PMID- 1916331 TI - [Hygienic substantiation of maximum permissible level of triethylphosphate in reservoir water]. AB - Data is presented on hygienic regulation of triethylphosphate (TEP) in the water of reservoirs. TEP is used in agriculture as plasticizer, as well as feedstock for organophosphides. Complex assessment of the results obtained made it possible to recommend 0.3 mg/l as MAC for TEP; the limiting index of harmfulness is general sanitary (BOD stimulation). PMID- 1916332 TI - [Structural and functional changes in the liver of pregnant rats and their fetuses exposed to cadmium, benzol and lead nitrate]. AB - Lead nitrate administered to noninbred rats with drinking water on the level of IO MAC (0.3 mg/l) during the whole period of gestation lead to the strengthening of hepatotoxic effect of cadmium chloride (7.5 and 15 mg/kg daily by gavage from the 1st to 20th day of gestation), manifest in significant increase of the hepatocytes alteration index, increase of the number of the pyknotic cells of reticuloendothelial system, increase of the degree of dams' liver hepatocytes dystrophy, decrease in the specific volume of megakaryocytes in the liver of their fetuses. PMID- 1916333 TI - [Hygienic evaluation of women's work in radio-manufacturing industry]. AB - Conditions and character of labour of women working in revolver production are determined by exposure to noise, contact with cooling oils, static field, monotony, hypodynamics, tension of the visual analyser, which leads to the stress of the functional systems of the organism, development of fatigue, decrease in labour productivity, increased morbidity level with temporary loss of capacity for work. A complex of health-improving measures on normalization of occupational factors, rationalization of labour and rest regimen, implementation of which would promote increase in the capacity for work of women engaged in revolver production. PMID- 1916334 TI - [Late sequelae of the effect of electromagnetic field on animals]. AB - Simple and complex forms of behaviour, gas composition and acid-alkaline blood status in rats following exposure to the electro-static field (ESF) and iraionization, as well as in their offspring were studied. It has been found out, that ESF combined with the negative polarity air ionization damage motor and sex activity, conditioned-reflectory activity, changes blood indices. The observed disturbances in the organism of parent animals influenced fetus development. PMID- 1916336 TI - [Complex evaluation of nitrogen-containing compounds]. PMID- 1916335 TI - [Experimental study of toxic properties of silicon tetrafluoride]. PMID- 1916337 TI - [Magnesium level in food rations and the prevalence of ischemic heart disease among the population]. AB - Virtual consumption of magnesium with food by an unorganized population of men aged 20-59 (780 people) living in Kiev has been studied. Insufficient magnesium content in the nutrition rations of the population (10% lower than the recommended values) has been observed. A correlation between the low magnesium consumption with food and prevalence of the ischemic heart disease, such risk factors of it, as hyperlipoproteinemia, arterial hypertension, redundant body weight. PMID- 1916338 TI - [Effect of radiating heat and physical exercise on adolescents]. PMID- 1916339 TI - [Necessity to change the paradigms in radiation hygiene]. AB - A question has been raised on the necessity to substitute the hypothesis of the biological effectiveness of ionizing irradiations as a paradigm of radiation hygiene for the linear--++non-threshold hypothesis. A comparison of the methodological substantiation fo both hypotheses and a conception of "acceptable risk" has been carried out. It is suggested, that the possibility of theoretical substantiation of setting standards for the radiation factor on the basis of adaptational hypothesis be acknowledge instead of the linear--++non-threshold conception which has lost its historic significance. PMID- 1916340 TI - [Methods of the control of non-ionizing radiation]. PMID- 1916341 TI - [Chronic effect of alternating electric field on genetic and morphometric indicators of the body]. PMID- 1916342 TI - [Data on substantiation of maximum permissible level of diethylchlorothiophosphate in atmospheric air]. PMID- 1916343 TI - [Toxicity of bis(2-methoxyethyl)ether of sebacic acid]. PMID- 1916344 TI - [Effect of fluorine after its complex intake]. PMID- 1916346 TI - [Transaminase activity during storage of blood serum and tissue extracts]. PMID- 1916345 TI - [Ontogenetic characteristics of the body response to chronic exposure to chemical substances]. AB - Chronic intoxication by carbon oxide and long-term exposure to hypoxic hypoxia produced more favourable reactions in animals, exposed to these in the early terms of ontogenesis. The observed regularity was not found under chronic exposure to styrene and epichlorohydrin ++. A supposition is made on the evolutionary predetermination of this effect pertaining to unfavourable factors of hypoxic nature. PMID- 1916347 TI - [Effect of adaptation to cold and physical training on heat emission during muscle work]. AB - People, for a long time exposed to cold and physical training or cold only, exhibit strengthening of thermal regulatory reactions aimed at the preservation of heat in the body in the state of rest, as well as during muscular tension. Adaptation of the organism to cold in the situation of limited motor activity lead to the increase of the thickness of the body "cover" under the conditions of rest in the cold due to the decrease of the temperature of skeletal muscles, while physical training in the cold facilitates stabilization of muscular temperature and, correspondingly, lessening of the thickness of the "cover". At the initial stage of muscular activity thermal regulatory reactions of the organism are aimed at the decrease in heat emission, which promotes accelerated heating of the muscles. PMID- 1916348 TI - [Creative heritage of A.N. Sysin and the current problems of soil hygiene]. PMID- 1916349 TI - [Hygienic evaluation of aldehyde transformation in atmospheric air (review of the literature)]. PMID- 1916350 TI - [A method of determining the level of furazolidone in the water medium]. PMID- 1916351 TI - [Photocolorimetric analysis of 2,4,6-trichlorophenylhydrazine in the air of the work area]. PMID- 1916352 TI - [Concentrating and determining the levels of microquantities of bancol in the air and water]. PMID- 1916353 TI - [Predicting the toxicity indicators and MPEL of various acids of the fat group, their methyl ethers and sodium salts in the air of the work area]. PMID- 1916354 TI - [Combined effects of substances on the taste of water]. PMID- 1916355 TI - [Use of a nuclear activation method in the study of toxicokinetics of chemical substances]. PMID- 1916356 TI - [Calculation of standards for physical development of children and adolescents using a programmable microcalculators]. PMID- 1916357 TI - [The hygienic evaluation of the preparation Putidoile and its effect on the sanitary state of water objects]. PMID- 1916358 TI - [The hygienic basis for the permissible concentration of the herbicide Pachtona in reservoir water]. PMID- 1916359 TI - [The hygienic regulation of trichloropropylphosphate in a water environment]. PMID- 1916360 TI - [The effect of pesticides and plant growth regulators on the morbidity in a rural population]. PMID- 1916361 TI - [The hygienic evaluation of crushed marble as filter material for water preparation]. PMID- 1916362 TI - [Dynamics of the survival of K. pneumoniae and P. aeruginosa in a water environment in experimental conditions]. PMID- 1916363 TI - [The complex hygienic regulations relating to the conditions of the use of pesticides on protected ground]. AB - Pesticide usage on protected grounds must be conducted with severe hygienic regulations. Its use must be minimised and in future replaced by biological plant protectors. PMID- 1916364 TI - [The uptake of mercury and arsenic from food rations by adults and children]. PMID- 1916365 TI - [Evaluation of the quality and shelf life of boiled fish sausage products based on microbiologic indices]. PMID- 1916366 TI - [The interrelation of psychophysiological indices and the level of motor activity in adolescent school children]. PMID- 1916367 TI - [Optimization of the functional state of primary school children using the rhythm of the teaching activity]. PMID- 1916368 TI - [The effect of the method of treating samples of dried fungi on the process of extracting cesium radionuclides]. AB - Most effective extraction of Cesium-137 radionuclide (near 100%) is produced by water during 48 h. The addition of salt (20 g/l) is not effective in this process. PMID- 1916370 TI - [Radiation conditions in the cabs of drivers of transports used for hauling radioactive materials and wastes]. PMID- 1916369 TI - [An analysis of the cytochemical oxidoreductase activity of the peripheral blood lymphocytes of rats exposed to 131I]. AB - Savage of rats with I131 at 2.5 MB/kg level followed with changing in red-ox processes in lymphocytes. It is caused not only by irradiation, but also by the indirect influencing of the thyroid gland's hormones. PMID- 1916371 TI - [The status of the higher nervous activity in animals exposed to microwaves in conditions simulating the intermittent work of radiolocators]. AB - Impulsive microwave irradiation (3 GHz, 400 imp/sec, duration of a pulse 2 microseconds, rotary speed--3.16 and 29 rpm) leads to the CNS activation in white rats. Activation was most at the slow antenna rotation (3 rpm). PMID- 1916372 TI - [The hygienic evaluation of the protection of winter wheat cultivated using intensive technology]. PMID- 1916373 TI - [The effect of sodium nitrite on the external respiration and the oxygen transport function of the blood]. PMID- 1916374 TI - [Evaluation of changes in memory and learning processes caused by pesticide poisoning]. PMID- 1916375 TI - [The properties of DDT isomers which determine its accumulation in the body and environmental objects]. PMID- 1916376 TI - [Possibilities of the chemical sterilization of soft contact lenses made of polyacrylamide]. PMID- 1916377 TI - [The oxidative phosphorylation of rat liver mitochondria in acute methanol poisoning]. PMID- 1916378 TI - [The basis for the maximum allowable concentration of cadmium in regard to its carcinogenicity]. PMID- 1916379 TI - [Social environmental factors and cardiovascular diseases of nautical personnel (review)]. PMID- 1916380 TI - [The history of the Department of General Hygiene of the Academician A.A. Bogomolets Kiev Medical Institute (on the 150th anniversary of the institute)]. PMID- 1916381 TI - [Photocolorimetric determination of carbohydrates in water]. PMID- 1916382 TI - [The determination of dimetpramide in water and biological media using liquid chromatography]. PMID- 1916383 TI - [The titrimetric determination of nitrites in aqueous solutions using an ascorbinometric method]. PMID- 1916384 TI - [Determination of heavy metals in the blood]. PMID- 1916385 TI - [More on the additivity when evaluating the combined action of several factors]. PMID- 1916387 TI - "New knowledge: the key to meeting the challenges of aging." The Gerontological Society of America, 44th annual scientific meeting. November 22-26, 1991, San Francisco, California. Program abstracts. PMID- 1916386 TI - [The correct determination of the allowable quantity of nitrates in vegetables in the drying process]. PMID- 1916388 TI - [Toxicological studies and their role in improving working conditions and preventing of occupational diseases of chemical etiology]. PMID- 1916389 TI - [Effect of hyperbaric oxygenation on the status of the oxidation- reduction system and bioenergetics in phosphorus-processing industry workers]. AB - Prolonged contacts with the hazardous substances in phosphorus processing caused noticeable changes in the oxidation-restoration system and bioenergetics. Therapeutic and preventive hyperbaric oxidation procedures improved the processes of bioenergetic supply in the body, which was caused by more active oxidation processes and decreased tissue hypoxia. PMID- 1916390 TI - [Use of bemitil for increasing the resistance of the human body to combined effects of carbon monoxide and heating microclimate]. AB - Basing on experimental data, it was established that single administration of 0.5 mg bemitil increased human resistance to carbon oxide in concentration 300 mg/m3. The use of bemitil optimized human body state in the conditions of the complex influence of carbon oxide and extreme heating microclimate. PMID- 1916391 TI - [Experimental study of toxic properties of dimethylcadmium]. AB - The article presents the results of research into the physical, chemical and toxicological properties of metallo-organic compound dimethylcadmium. Through functional, morphologic and biochemical technique, in acute, pre-acute and chronic experiments on animals, established were the major toxicometric parametres, the substance's action on the blood system, respiration, functioning of the kidney, the liver, the CNS and the gonads. The data showed that, if inhaled, dimethylcadmium was more toxic than the other cadmium non-organic compounds, being a polythropic poisonous substance with particular damaging effects on the kidney, the liver, the CNS and the respiratory organs. The MAC for dimethylcadmium concentrations in the working zone air was proposed at 0.001/0.005 mg/m3. PMID- 1916392 TI - [Effect of potassium bichromate on mucous membranes of the nasal cavity and paranasal sinuses in animal experiments]. AB - Common white rats were used in the study of potassium bichromate (PB) influence and paranasal sinuses mucosae. Single 2-10 PB endonasal introductions were performed on hemostatic collagenic sponge and on paraffin. PB revealed ability in significant causing chronic atrophic rhinosinusitis , and demonstrated weak carcinogenic properties through the induction of some nasal tumours after a prolonged contact of the nasal mucosa with the substance. PMID- 1916394 TI - [Sanatorium rehabilitation of deep coal mine workers of Donetsk after myocardial infarction]. AB - The article contains a study of 529 myocardial infarction cases in coal miners with provisional assessments of their health states after the rehabilitation course. Inadequacy of the resort treatment procedures was established, the clinico-functional examinations of the patients were irregular and limited to one or two procedures, which hampered the objective assessment of the measures taken. The drug treatment procedures were also inadequate both in respect of the patients' health conditions and with regard to specific drug prescriptions, dosages and frequency of administration. The results of the prolonged study revealed that 50% rehabilitation cases were unduly handled and returned to clinic with health complications after 6 months. The rehabilitation course did not include the psychotherapeutic rehabilitation component, which would be of paramount importance for the patients under the new health circumstances. Out patient admission epicrises were not performed whatsoever, or were of a low quality, thus accounting for future rehabilitation failures. PMID- 1916393 TI - [Current problems of epidemiology and toxicology of the occupational action of lead (review of the literature)]. AB - The focus of current research on industrial lead toxicity is on the definition of dose-response relationships, particularly++ at low levels of exposure. Major interest surrounds the development of biochemical and physiologic markers of subclinical toxicity. Need exists to better delineate the toxicity of lead on the peripheral and central nervous system the kidneys, the cardiovascular system and the reproductive organs. To obtain more accurate information on cumulative individual exposure to lead, future research on lead toxicity will increasingly utilize X-ray fluorescence (XRF) analysis for determination of the lead content in bone. PMID- 1916395 TI - [Prevalence of hypertension among railroad engine operators at a metallurgical plant]. AB - The article comments on a study of the labour conditions peculiarities of industrial rail-way engine operators and the epidemiology of hypertension disease in this professional group. 962 persons (both mechanics and their subordinates) were examined, all of them males, 20-59 years of age, with the duration of work: less than 10 years--366 cases, 11-20 years--483 cases, over 20 years--113 cases. The analysis of hypertension prevalence revealed that the morbidity rate was markedly higher among the engine teams' personnel as compared with the depot workers. The morbidity rate difference between the industrial rail-way engine mechanics and main-line engine mechanics was insignificant. The high morbidity rate necessitates improvements of the labour conditions, e.g. working shift cuts, establishment of physical rehabilitation and psycho-emotional relaxation units, as well as rational diet. PMID- 1916396 TI - [Indicators of mental and physical work capacity during reserpine treatment of patients with arterial hypertension working under neuro-emotional stress]. AB - The article deals with reserpine influence on mental and physical working capacity, psychic state and professionally relevant functions of memory and concentration in 36 male patients of 50 +/- 2.0 years of age suffering from arterial hypertension and engaged in professions characterized with extreme neuro emotional stress conditions ( enterprise managers). It was shown that reserpine induced a stable and significant hypotensive effect, improved the physiological indices and physical working capacity, but hampered the mental and cognitive function activity, concentration and short-term memory. Reserpine cannot be recommended for drug therapy in out-patient departments in the treatment of the patient professionally engaged in stable emotional stress conditions. PMID- 1916397 TI - [SAN testing using a programmable microcalculator]. PMID- 1916398 TI - [Data on hygienic standardization of N,N-diethyl-2-chloroacetamide in the air of the work area]. PMID- 1916399 TI - [Reaction of the nervous system cells to infrasound]. PMID- 1916400 TI - [Maximum permissible exposure levels of harmful substances in the air of the work area ratified by the USSR Ministry of Health in 1989]. PMID- 1916402 TI - [Changes in various indicators of nonspecific immunity in operators exposed to high environmental temperature]. AB - 30 degrees C temperature conditions caused no vivid changes in the non-specific immunity indices in operators. Temperature levels at 40 degrees C and 60 degrees C caused non-specific immunity marked decrease. The changes registered immediately after exposing to high temperatures were less vivid as compared to those registered three hours later. Repeated exposing to 60 degrees C 1 week later displayed more expressive shifts in the non-specific immunity indices. PMID- 1916401 TI - [Functional state and development of diseases of the locomotor system in seamstresses in relation to their work characteristics and degree of physical exertion of the hand muscles]. AB - Physiological and clinical on-the-spot studies were performed of the labour conditions in 3 groups of female sewing-machine operators (respectively, engaged in making women's dresses, men's suits and men's coats). The analysis performed revealed different degrees of physical load and fatigue in the operators depending on the occupational peculiarities. Specific features of the peripheral nervous system and locomotor system disorders were studied in details, along with the causal relationships underlying the degree of physical load and fatiguability, overstrain development and cumulation. The results of the study were used as a basis for setting Health-Related regulations for sewing-machine operators. PMID- 1916403 TI - [Current problems of occupational pathology]. PMID- 1916404 TI - [Epidemiology of pneumoconiosis and dust bronchitis in machine-building industry workers]. AB - The article provides a study of pneumoconiosis morbidity rate in machine-building industry workers in 1967-1986. The pneumoconiosis prevalence was ranging from 3.9 to 0.8 cases per 1000 medical examinations performed. The disease's initial forms were predominantly diagnosed through considerably frequent (30%) cases of anthraco-tuberculosis. More complicated forms of dust bronchitis were studied in 1971-1988 and registered at approximately 1 case per 1000 medical examinations. A vivid trend towards pneumoconiosis morbidity decrease and respective age and duration of work indices' growth was found in the latter decade, which was explained by more persistent measures taken towards working conditions improvement. PMID- 1916405 TI - [Tattooing of the bronchial mucosa in patients with pneumoconiosis and dust bronchitis]. AB - Medical examinations were performed of 138 pneumoconiosis (PC), 123 dust bronchitis (DB) cases and 28 pulmonary cases of non-occupational etiology. Fiber bronchoscopy with biopsy of bronchial mucosal tissue and, if necessary, transbronchial biopsy were performed in all the cases. Bronchial mucosa tattooing in persons exposed to different industrial aerosols did not depend on the forms of PC, DB and the diseases' stages. Nevertheless, it was established that, at more expressed stages of the disease and in case with complications (anthraco tuberculosis), tattooing of the bronchial tree was more developed. In 92.3% cases, tattooing was formed in persons exposed to industrial aerosols containing more than 10% free silicon deoxide. On the tissue level, the morphologic substrate of the tattooing was lymphatic nodes obturating the coniophages and the coniotic infiltration of the bronchial mucosa connective tissue. Anthraco tuberculosis induced specific inflammation contributed to the infiltration process due to the lymphodynamic disorders caused by lymphadenopathy. PMID- 1916406 TI - [Effects of fixed working postures on the functional state of the neuromuscular system of the workers]. PMID- 1916407 TI - [State of central and regional hemodynamics in riveters depending on the type of blood circulation]. AB - Tetrapolar rheovasography was used to medically examine 54 riveters, of equal age and duration of work, who were exposed to the complex action of low-intensity vibration and noise. The central, cerebral and peripheral hemodynamic indices were assessed depending on the blood circulation type with dew account of the current views on the hemodynamic norms. Identified were differences in the absolute figures of most indices of central and cerebral hemodynamics depending on the blood circulation type. The 'levelling' of the peripheral blood circulation indices was performed by initial vibration disease pathologic developments in vascular tension. It can be concluded that the hypokinetic type of blood circulation is a risk factor which should be taken into account in selecting the occupational criteria for riveters. PMID- 1916408 TI - [State of the pancreas in persons with alcohol-related risk factors]. AB - Clinico-laboratory and instrumental techniques were used to investigate the pancreas states in alcohol abusers at preclinical stage. Examined were 74 persons, 24-31 years of age, with established alcohol-related risk-factors, who would consider themselves healthy. The character and forms of alcohol addiction were determined by a psychiatrist. Complaints were studied in the group which fell into astheno-vegetative syndrome (56.2%), dyspeptic disorders (32%) and pain (14.1%). Ultrasound scanning of all the cases was performed. Pancreas tissue echostructure changes were detected in 16% cases, including fibrosis and edema in 7 and 5 cases, respectively. Hydrochloride methionine intraduodenal testing was performed to assess the pancreas external secretion indices. 98.6% cases manifested changes in external secretory function, e.i. increased concentration and secretion of amylase, decreased concentration and secretion of bicarbonates in the stable volume and rate of pancreatic juice secretion. PMID- 1916409 TI - [Current status of hygienic assessment of industrial impulse noises (review of the literature)]. PMID- 1916410 TI - [Immunity and non-specific defense in workers exposed to chronic action of low dosage ionizing radiation (review of the literature)]. AB - The article contains a review of some medical literature data on the current state of non-specific protection and immunity in persons exposed to chronic actions of low-dosage ionizing radiation. Both in the 60s, when the occupation related levels of ionizing radiation not infrequently exceeded MALs, and in the 80s, when such levels were considerably lowered, most researchers stressed the possibility of inhibiting the non-specific protection, T- and B-systems indices, formation of allergies and autoallergies. The changes and developments are considered by the authors a result of a complex action of both radiation and non radiation-induced industrial factors. PMID- 1916411 TI - [Methodology problems of in-depth studies of occupational diseases]. AB - The article sets forth some methodological issues related to the substantial analysis of occupational morbidity. Confirmed is the necessity of stratifying the morbidity along the line of individual professions and professional groups, of inviting scientists from technical research centres, practical physicians for elaborating preventive measures in occupational medicine. PMID- 1916412 TI - [Effects of work conditions of women on the outcome of pregnancy and labor]. AB - Working under the occupational conditions of Gr. 3 of hazardness is a risk-factor with respect to the reproductive function in women. Working under such conditions before pregnancy and its early stages (before it was diagnosed) is fraught with complications for the pregnancy course and for the fetus. Creation of normal labour conditions immediately after pregnancy has been diagnosed is capable of protecting the mother's health, but it cannot guarantee the fetus' viability. The proposed measures influenced positively pregnancy terminations in the women working at the KAMAZ Automobile Plant. PMID- 1916413 TI - [Sanitary-hygienic assessment of polyurethane foam contents of KH-96 used in sealing of ventilation equipment in coal mines]. AB - The article contains a hygienic and chemical assessment of the KH-96 polymethane foam plastic material used in air hermetization in coal mines. A set of measures is proposed to ensure safety in working with the material. PMID- 1916414 TI - [Assessment and ways of improving sanitary-hygienic conditions of crane operator work]. PMID- 1916415 TI - [Retrospective analysis of carcinogenic hazards of beta naphthylamine and benzidine production as a stage of an epidemiological study of tumors in workers engaged in aniline dye industry]. PMID- 1916416 TI - [Effects of smoking on several indices of external respiration in practically healthy workers of radiochemical industry (a dynamical study)]. PMID- 1916417 TI - [A multi-chamber model of quartz dust kinetics in the pulmonary region during chronic inhalation exposure in rats]. AB - The contributors propose a multichamber model for the assessment of dust particles' concentration, elimination and translocation in deep pulmonary zones. The choice of the model structure is dominated by the following criteria: that dust penetration into the interstitial pulmonary tissues and its translocation to the lymph nodes can be performed by non-phagocytized particle only; that these processes depend on the degree of dust-induced lesions in the macrophages and the growth of compensating neutrophilic phagocytosis; that part of the penetrating particles would continuously return to the free surface of the pulmonary zone together with the mobilized interstitial lung macrophages. The model adequately corresponds to the experimental data obtained in prolonged inhalation experiments, and imitates the kinetic effects related to severe damages and protection of the pulmonary clearance macrophage mechanisms. PMID- 1916418 TI - [Interventional ultrasound in the diagnosis and therapy of fetal malformations]. AB - The author discusses his own experience in ultrasonically guided needle diagnosis and treatment of foetal malformations. Over the period from January 1, 1980 to May 1, 1985 1266 amniocenthesis, 50 chorion biopsies, 32 heart punctures, 15 craniocenthesis, 10 decompressions of obstructed urinary tract, 1 urinary shunt catheter placement, 2 ovarian cyst punctures, 1 thoracocenthesis and 110 intraamniotic instillations of prostaglandins and hypertonic saline solution, were performed. The author concludes that ultrasound is of major importance in antenatal diagnosis and treatment of foetal malformations, but that the clinical potential of these procedures should not be under-or over-estimated. PMID- 1916419 TI - [The effect of early rehabilitation in patients with myocardial infarct determined by echocardiography]. PMID- 1916420 TI - [Cardiac trichinosis--echocardiographic study]. AB - Trichinosis is an intestinal and tissue infection of man caused by Trichinella spiralis. The most frequent and serious complication is myocarditis. M-mode and two-dimensional echocardiographic studies were carried out on 16 patients with clinical manifestation of trichinosis. The parameters of the left ventricular function, measured by echocardiography were examined, and the results were compared with the same parameters in 50 normal individuals. In 11 patients a variety of morphologic findings, like pericardial effusion, adhesions, focal endomyocardial fibrosis, dilated left ventricular cavity, were found. In one patient intra cavitary thrombus was bound. Pathologic parameters of the left ventricular function were registered in 15 patients. PMID- 1916421 TI - [Relation between Doppler echocardiography and the surface area of the mitral valve]. AB - The Doppler signal of mitral flow velocity depends not only on the pressure drop across the mitral orifice, but on the volume flow also. Since the slope of the maximum velocity curve and the rate of decrease of pressure drop during diastole are influenced by the degree of obstruction, we compared the findings of the Doppler examination in our patients with different mitral valve areas determined by 2-D echocardiography. PMID- 1916422 TI - [Echotomography of malignant tumors of the liver]. AB - The echotomographic primary liver carcinoma can be hyperechogenic and hypoechogenic, or both. In metastasis, in addition to the pattern of primary carcinoma end-lesion changes are also visible, or liver parenchyma can be diffusely heterogeneous. The echotomographic findings of primary and secondary liver tumours cannot be differentiated. The origin of metastasis in the liver cannot be established by echotomography. However, a typical echotomographic picture can be obtained in some carcinoma (colon carcinoma). PMID- 1916423 TI - [Echographic evaluation of gallbladder contractility]. AB - The advantages of echography (EG) in the follow-up of morphologic and structural changes of cholecyst are wellknown. In this paper we tried to prove the possibilities of echography in the evaluation of cholecyst contractility as the reflection of its function. In 70 patients peroral cholegraphy (POH) and EG were performed simultaneously. In POH the congruence of contraction intensity evaluation, made visually and measured, was present in 74.3% of the cases, and EG in 71.4%. In relation to visual evaluation, the measurements in cm proved to be reliable. The evaluation of cholecyst contractility by measurements in cm was statistically congruent in POH and EG. According to the results of investigation, the measurements of cholecyst length and width in the left oblique position were more reliable. The total length was a more constant measure of cholecyst size. The contractility was satisfactory if 1/3 of total width (a) and length (b) was approximately equal to the total of width and length before (A) and after (B) stimulation. This can be expressed by the following formula: K 1/3 (a+b) A (a+b) B (a+b). The echographic evaluation of contractility can be used as an additional procedure to cholecyst investigation and that it can replace POH completely. PMID- 1916424 TI - [Diagnosis of periorbital diseases by means of ultrasound]. AB - The ophthalmology was one of the first medical branches which used ultrasound in diagnostical purposes. The structure of the eye, with the large vitreous body, through which the ultrasound waves pass without attenuation, is highly appreciated in ultrasound examination, thus the diagnostical results of ocular diseases are extremely good. On the base of our rich ophthalmological experience we left the scope of the eye and the orbit, and made ultrasound examinations of the head and the face. The echograms of two patients presented original patterns: one was malignant melanoma of the skin with typical echograms performed by A and B scannings, and the other case was the Mikulicz disease with typical echograms. Original echograms of these patients can be considered as a contribution to ultrasound diagnosis of paraorbital diseases. PMID- 1916425 TI - [New aspects in the diagnosis of fetal malformations using ultrasound]. AB - The article deals with new ultrasound diagnostic aspects of foetal malformations. The frequency of such events in Yugoslav population is described and importance of their early detection is emphasized. The following features of foetal malformations are discussed: systems, characteristics, possible aetiopathogenesis, ultrasound detection and sonographic signs. Some congenital malformations are illustrated by original ultrasound and postnatal pictures. Their postnatal and intrauterine corrections are examined. Consequently, the optimal possible abortion is discussed. The analysis concerns the practical classification of congenital malformations into serious, incorrectable, incompatible with life, recommendation for abortion, and into light, correctible anomalies. Exclusion of pathologic events in risk-groups and during routine practice is emphasized. Possible errors (false-positive and false-negative diagnosis) and difficulties in the definition of small structural anomalies are presented. Complementary diagnostical methods are also enumerated. PMID- 1916426 TI - [Human placental lactogen levels in normal pregnancy monitored by serial ultrasound]. AB - Parallel to the great use of ultrasound in diagnostical purposes the interest for biological effects of ultrasound is growing every day. The present studies of the biological action of ultrasound concerned the cytogenetic investigations as well as those of animals and men. Taking into account that the extrapolation of results from animals to men is uncertain all data obtained in human population are of utmost importance. We tried to define the possible biological action of routine diagnostical ultrasound on foetoplacental unit. Women with physiological pregnancy were exposed to ultrasound during regular antenatal control examinations in the 20th, 30th and 38th week of gestation. The follow-up concerned HPL levels in the serum 1 hour before and 1 hour after exposure to ultrasound. There was no significant difference in concentrations of the examined hormone in both blood samples. PMID- 1916427 TI - [Standard fetal growth curves--current aspects of their utilization]. AB - The total 3492 complete measurements were performed in order to make asymptomatic curves of intrauterine foetal development. Of this number 1756 measurements concerned the biparietal diameter (BPD) and 1736 the abdominal diameter (ABD). Measurements of the biparietal diameter were done from the 13th to the 41st week of gestation. The mathematical processing of all serial groups was done according to defined algorithm. On the basis of statistical analysis of distribution frequency and dispersion parameters the necessary findings were obtained. Thanks to these findings asymptomatic curves of intrauterine foetal development were made. PMID- 1916428 TI - [Sonosalpingography and/or hysterosalpingography, advantages and disadvantages]. AB - Sonosalpingography is a new procedure in the examination of the passage of the uterine tube. It was first used by Dr. Richman from the United States. On the basis of the comparison of sonosalpingographic and histerosalpingographic findings it was concluded that in spite of advantages (simple and fast method) sonosalpingography should be indicated only in cases where hysterosalpingography is contra-indicated. PMID- 1916430 TI - [Sonographic monitoring of follicular maturation]. AB - In recent years the interest for the evidence of ovulation and its follow-up has increased. This increase is especially evident in the field of out-body insemination. The ultrasound follow-up of ovulations is performed in the case of the growth of the follicle; determination of the ovulation ring; and observation of the Douglas free liquid. The authors present values of the follicular diameter on the 14th day of gestation in 34 patients with spontaneous, stimulated and induced cycles. In their opinion this procedure is a very useful method which, in addition to other parameters, enables a good inspection into the functioning of the ovary. PMID- 1916429 TI - [Biopsy of the chorionic villi with the aid of ultrasound in the diagnosis of chromosome disorders in the 1st trimester]. AB - Chorion frondosum biopsy is a method of antenatal diagnosis based on the chorion villi cell analysis, with the aim of detecting hereditary disorders of chromosomal and genetic origin. The method was applied at the Department of Gynaecology and Obstetrics in women with undesired pregnancy from 8 to 12 weeks. This was the first phase of our investigation. Chorion frondosum samples were taken by Jackson's forceps and "Portex" cannula for transcervical aspiration. The role of ultrasound, as a component part of this method, is pointed out in the paper. Ultrasound was applied in a way not to damage the embryo and its membranes, and to locate chorion frondosum--the site of taking the appropriate chorionic villi. The success of detection of foetal chromosomal constitution in our study was 84%. Chromosomopathy was registered in on case. The foetus had tetraploidy--92, XXYY. PMID- 1916431 TI - [Value of echotomographic measurement of the diameter of the head and abdomen and the length of the femur in the determination of body mass in neonates]. AB - A formula for the antenatal assessment of the body mass of a newborn infant is suggested. It consists of the 3 foetal parameters measured by ultrasound: the biparietal diameter, the transversal abdominal diameter and the femur length. The advantage of this formula was established by a good correlation between these parameters and body-mass after birth in comparison to formulae made of a single parameter or of a combination of two parameters. The described procedure was compared with other trials. The formula was especially convenient for the measurement of longitudinal components, as foetal femur length. In this way the approximate three-dimensional feature is obtained. PMID- 1916432 TI - [Sonographic prediction and detection of ovulation]. AB - The aim of the study was to define the role of sonography as a separate method in prediction and confirmation of ovulation. The growth of the follicle over the period from the 10th to the 17th day of menstruation was sonographically followed up in 63 spontaneous and induced cycles. It was found that sonography was a quick and simple method. As separate method it can be used for the confirmation of ovulation, prevention of hyperstimulated ovarian syndrome and determination of the best time for artificial insemination. In combination with the other procedures it is convenient for prediction of ovulation. PMID- 1916433 TI - [Doppler echocardiography in the evaluation of prosthetic valve function]. AB - The limitations of invasive and noninvasive procedures, including M-mode and 2-D echocardiography, in the follow-up of patients with prosthetic heart valve replacement, are numerous and well known. Doppler echocardiography helps the functional evaluation of prosthetic valves by reliable detection of valvular regurgitation through a malfunctioning prosthetic valve or due to paravalvular leaks. On the other hand, serial determinations of the values of pressure drops or effective valve orifice areas, calculated from the half-time pressure, enables the diagnosis of prosthetic valve obstruction or dehiscence. The results in the assessment of prosthetic valve function by Doppler echocardiography in a group of operated patients, are reported. Signs of prosthetic valve malfunction were not present in 6 patients with mitral valve prostheses and two patients with two valve-prostheses (mitral and aortic) in the group ob 13 evaluated patients. In two patients with Bjork mitral valves mitral regurgitation was found. It was due to valvular leakage in one patient and to paravalvular leakages in the other. In both patients with aortic prosthetic dysfunction a paravalvular leak was diagnosed. There was an invasive proof of prosthetic regurgitation in the same four patients. The only patient with biologic mitral valve prosthesis presented a significant flow obstruction. PMID- 1916434 TI - [Continuous and pulsed Doppler in the examination of arterial circulation in the extremities]. AB - The authors present their experience in the investigation of arterial circulation by continuous and pulsed Doppler. The results obtained by Doppler's method were correlated with other noninvesive methods and arteriography. Arteriographic findings were scored by Bollinger method. A statistically significant difference of the flow and systolic pressure values was found between angiographically normal subjects and those with single and multiple lesions. The authors conclude that ankle flow and systolic index measurements, obtained by Doppler technique, are influenced by the degree, extensiveness and localisation of arteriosclerotic lesions on the lower limb arteries. The method was successfully applied in the control of the effects of medicamentous and surgical therapy. PMID- 1916435 TI - [Immunologic response to microorganisms from a polluted ventilation system in a working environment]. AB - Authors point out the morbidity of employees working in ventilation systems contaminated with various microorganisms. They analysed 96 workers exposed to air conditioning system (Group A), and 71 workers (Group B) breathing normal ambient air. The workers of both groups were subjected clinically by functionally and immunologically. Preparation of antigens "MMM" (Monday morning miseries) was used as an original method by Ajello et al. for producing antigens from systemic mycotic agents and subsequently modified. The aim of the present study is to evaluate the possibility of using ELISA in clinical practice for respiratory allergy diagnosis, and especially Hypersensitivity pneumonitis. Atopic status was determined by skin prick tests with common airborne allergens including Dermatophagoides pteronyssinus, ragweed, grasses and Aspergillus fumigatus., by Enzygnost--IgE (Behringwerke AG, Marburg) and for specific IgE by RAST technique (Pharmacia, Uppsala). The skin prick tests were performed with "MMM"-antigens. PEFR (Peak Expiratory Flow-Rate) was measured by using a Wright's peak flow meter. PEFR was recorded on Monday (first day at work) and Friday (the end of the working week). Measured values of PEFR in both groups of employees from Monday to Friday were elaborated by the Wilcoxon test. RESULTS AND DISCUSSION: Culture of scrapings from air conditioning vents were obtained and water from the humidifier system also cultured. They were grown: T. vulgaris, Aspergillus fumigatus, Thermoactinomyces vulgaris and others. Results of questionnaires, clinical evaluation and diagnostical procedures in employees of Group A and B are as follows: Thirty eight workers in Group A had a positive clinical history of "Monday illness". In the symptomatic Group A we found in 8 cases abnormal chest roentgenogram. Further, there was no correlation between the presence of antibodies (ELISA) against MMM and pulmonary function abnormalities, as measured by either spirometry or DLCO. Further, we found good agreement between ELISA and prick test results with antigen MMM. Wilcoxon test showed a statistically significant difference between the two groups (0.01). The median or central value of PEFR reduction in Group A is 10.23 per cent, and in Group B 1.49 per cent. A 30 per cent reduction of PEFR was observed in 5.21 per cent of subjects in Group A. Exposure to ventilation systems contaminated with Thermophilic actinomyces may be responsible for increased morbidity and reduced performance of employees working in air conditioning systems. Particularly the main filter should be checked regularly. Moreover, regular microbiologic examinations of dust and water from air preventing chronic obstructive lung diseases in employees working in areas served by contaminated air conditioning systems. PMID- 1916436 TI - [Determination of T lymphocyte subpopulations in malignant lymphoproliferative diseases]. AB - The aim of this work was to investigate T cell subset composition of peripheral blood cells in patients with acute myeloid leukaemia, acute lymphoblastic and chronic lymphocytic leukaemia, by enumerating T cells positive for receptors for sheep erythrocytes (E-RFC, A-RFC) using the method of E-rosette, and for CD3, CD4 and CD8 antigens, by indirect immunofluorescence technique, using the monoclonal antibodies of the OK series. The study was performed on 57 patients without therapy and 46 healthy persons. The results of enumeration of T cells and their subsets obtained in the stage of the disease when the total leukocyte count was below 20 x 10(9)/L, were markedly decreased in all three types of leukaemias. The most significant decrease of relative count of T cells and their subpopulations was obtained in CLL patients. Analysis of T cells subsets and their ratio in CLL patient in the stage of disease when the total leukocyte count as higher than 20 x 10(9)/L, demonstrated the most pronounced decrease of total T lymphocytes and CD4+ cells. The relative count of the "active" (A-RFC)T cells and CD8+ cells did not change, and was the same as in the patients suffering from CLL with a lower leukocyte count. PMID- 1916437 TI - [Reference values in immunodiagnosis: the approach using the Senieur protocol]. AB - In an attempt to standardize the normal values for immunological tests it is necessary to establish strict admission criteria. The EURAGE Concerted Action Programme on Ageing of the European Community described the SENIEUR protocol with criteria for immunological studies in man, based on clinical and laboratory information. Our results on humoral and cellular components of immunity in dependence of age, according to SENIEUR protocol admission criteria are presented. PMID- 1916438 TI - [The effect of serum on NK cell activity]. AB - In the immunosurveillance of the development and spread of tumors NK cells seem to have a major role. For this reason, the assessment of NK cell activity of patients with a malignant disease represents a significant immunological parameter. The results of our study indicate that for the group of 26 breast cancer patients basic NK cell activity is significantly below NK cell activity for healthy controls. In a previous set of experiments we found that a short term incubation of peripheral blood lymphocytes of these patients in medium, alone, gives a considerable augmentation of impaired basic NK activity, so we made an attempt to determine the influence of autologous serum on NK cell activity. Our data indicate that both healthy serum and autologous serum of breast cancer patients, in the early stage of disease, give a similar degree of inhibition of NK cell activity, after in vitro cultivation of PBL, when compared to PBL cultured in medium with FCS, and that only sera from breast cancer patients with advanced disease had a greater inhibiting effect. Incubation of PBL of healthy controls with autologous healthy sera showed a somewhat greater inhibitory effect on NK cell activity than sera from breast cancer patients in the early stage of disease. We consider that monitoring of NK cell activity after incubation with autologous serum may give not only a better assessment of NK cell activity of these patients in vivo, but also possibilities fro investigating factors which lead to serum-induced modulation of NK cell activity. PMID- 1916440 TI - [The occurrence of diabetes and organization of diabetes health services in Yugoslavia]. AB - According of data of the antidiabetic medical service, in Yugoslavia there are registered 380,000 patients with diabetes. This makes 1.70% of total population. In northern parts of the country, with a higher development of agriculture, industrialization and urbanisation, the prevalence of diabetes is over 2%. In southern parts, mostly highlands, the prevalence of diabetes is less than 1%. According to needs, the antidiabetic medical service is better in developed parts of the country with higher prevalence of diabetes. Altogether in Yugoslavia, there are 8 central institutions for diabetes and endocrinology, 81 dispensaries, and 130 out-patients units for diabetics. The antidiabetic medical service is in progress, qualitatively and quantitatively, along with the progress of the prevalence and incidence of diabetes. PMID- 1916439 TI - [The importance of hormone receptor determination in breast malignancies]. AB - Estrogen and progesterone receptor phenotypes expressed as "positive" or "negative" are widely used for the determination of estrogen dependence of primary breast tumor. In our opinion the receptor phenotype, so important for biological and clinical behavior of tumor, should consider the quantitative values of receptor content. For this purpose, the correlation between quantitative estrogen versus progesterone receptor content and the distribution of the quantitative estrogen and progesterone receptor content within some parameters of tumor and tumor-host was analyzed. Our results show: There is the same range of correlation between estrogen versus progesterone receptor content in tubular tumor type, invasive ductal and lobular carcinomas, and in all three histologic grades; Histologic type influences the estrogen dependence through histologic grade. There is no difference in distribution of the quantitative estrogen and progesterone receptor content when corresponding grades of tubular tumor type, invasive ductal and lobular carcinomas are compared; In premenopause status histologic grade defines different groups with regard to the quantitative progesterone receptor content; In postmenopause status histologic grade defines different groups with regard to the quantitative estrogen and progesterone receptor content; In tumors with histologic grade I, transition of pre to postmenopause status is connected with a significant increase of the frequency of the high quantitative estrogen receptor content; In tumors with histologic grade III, transition of pre to postmenopause status is connected with a significant increase of the frequency of the low quantitative estrogen and progesterone receptor content. PMID- 1916441 TI - [Modification and visualization of the allergic reaction in isolated and innervated organs]. AB - The model-systems, as are isolated innervated organs (IIO) taken out from the sensibilized animals, could improve the screening of immunomodulators. The stimulation of extrinsic motor nerves of IIO contemporary with antigen-antibody reaction (AAR) produced two types of responses. The first type was the increase of tonus and the induced contractions. The second type of reaction was the decrease of the contractions. The first type of response was recorded when the motor nerve was cholinergic and the second type of reaction was recorded when the motor nerve was adrenergic-purinergic (vas deferens). Guinea-pigs and rabbits were the most convenient experimental animals. The preparation of mice and rats for the immunological experiments should be improved, the more so from mice and rats, since useful model-systems could be obtained. Human serum and white of eggs were the most convenient antigens. The immunomodulators thymopentin and muramyl dipeptide injected before or after AAR did not change the tonus and induced contractions in comparison with control ones. PMID- 1916442 TI - [Thyroiditis]. AB - We reviewed the results of the long term study of incidence, clinical characteristics, some etiological possibilities and pathogenetic mechanisms in inflammatory diseases of thyroid gland. Among persons who suffered of acute thyroiditis we presented the most frequent causes and prominent clinical characteristics in the course of the disease with special interest for predisposing factors. Contrary to the most frequent opinions, the number of cases with subacute (de Quervain) thyroiditis is so similar to the number of cases with Graves diseases. For these reason we concluded that subacute thyroiditis is important medical problem, in spite of its benignity. Even well known clinical characteristics and therapy of subacute thyroiditis, etiology and pathogenetic mechanisms are not well estimated. The group of chronical thyroiditis described as autoimmune thyroiditis, indicates on etiology of this heterogeneous group of thyroid diseases. Modern aspects of therapy are shown at the end of the study. PMID- 1916443 TI - [Determinants of susceptibility to the induction of autoimmune diabetes in inbred strains of rats]. AB - Interleukin 2 (IL 2) proved to be important for the generation of autoreactive T cells in the pathogenesis of different autoimmune disorders, including diabetes. Also, we have previously shown that lymphoid cells obtained from inbred strains of rats Dark August (DA) and Albino Oxford (AO) exhibited a genetically determined difference in their ability to produce IL 2. In this study, in DA and AO rats, we analysed the susceptibility to the induction of autoimmune diabetes with multiple subdiabetogenic doses of alloxan. Rats were injected i.v. with 25 mg/kg b.w. of alloxan in 5 consecutive days. All DA rats developed moderate and persistent hyperglycaemia 15 days after the induction. In contrast, AO rats failed to develop the disease after the same regimen of induction. When the induction was made in (AO x DA)F1 rats, all of them developed the disease similar to the susceptible parental DA strain. However, the onset was delayed (the 40th day after the induction) and the glycaemia was constantly lower than in DA rats. Our results indicate that the difference in the response to the induction of autoimmune diabetes between susceptible DA strain, being high IL 2 producer, and resistant AO strain, being low IL 2 producer, is genetically determined. The results also suggest that this control could involve the gene determining the level of IL 2 production in DA and AO rats, thus signifying that the susceptibility to the induction of this form of autoimmune diabetes could be related to the level of IL 2 activity. PMID- 1916444 TI - [The significance of individual inhalation allergens in the sensitization of children with respiratory allergy]. AB - Four hundred children were skin tested with following allergens: Dermatophagoides pteronyssinus, moulds, animal dander (mixture of dog, cat, sheep and horse dander), tree pollens, weed pollen (Ambrosia artemisifolia), and six grass pollens, as well as three nutritive allergens in children less than three years of age. Results demonstrated that in 200 children with perenial rhinitis and/or asthma. Dermatophagoides gave positive results in over 90%. In 200 children with pollen allergy, grasses were major allergens, and among them Timothy (Phleum pratense) gave over 90% of positive results. It is to be concluded than skin testing with many inhalatory allergens is not necessary in patients with typical clinical picture. Skin test with Dermatophagoides and Timothy should be done, and further evaluation taken into consideration only if these are negative. PMID- 1916445 TI - [Clinico-laboratory characteristics of physical urticaria]. AB - Physical urticarias represent a specific reaction of the skin, which is characterised by local erythema, edema and pruritus at the site where the physical stimulus has been applied. However, local changes can be associated with various systemic manifestations. Specific cutaneous reactions due to physical factors may be the first manifestation of a systemic and/or infectious disease, which should be taken into account as physical urticarias generally occur in young patients. In view of the above mentioned, as well as unpredictable course of the disease and relatively limited therapeutic effects, the etiology and pathogenesis of the physical urticarias are one of the most interesting fields of investigation in contemporary medicine. PMID- 1916446 TI - [Effect of ranitidine on the pharmacokinetics of theophylline in patients with obstructive pulmonary disease]. AB - Investigations were performed on 20 patients with mild and moderately severe forms of bronchiale asthma or chronic obstructive bronchitis. Theophylline for oral use (sustained release form) and Ranitidine (second generation H2-blocker) were used in the first group of patients (7 females and 3 males, average age 37.9). Dosage of theophylline from patients sera was monitored at 3, 6 and 12 hours, beginning with the initial morning dose. The second group of patients (9 females and 1 male, average age 46.3) were on Ranitidine therapy, along with 250 mg intravenous theophylline-ethylene-diamine. Fractionated dosage of theophylline was done within 12 hours. Pharmacokinetic parameters were calculated according to the concentration of theophylline in the sera of patients in the second group. Significant differences were not found by statistical analysis (T-test) in the pharmacokinetic parameters of theophylline although significantly higher concentrations of theophylline were found in the sera of patients in the first group. This indicated that there are individual differences on the metabolism of theophylline drugs with concomitant use of Ranitidine. PMID- 1916447 TI - [Proteinuria in dermal vasculitis (incidence, degree and possible mechanisms of onset)]. AB - The paper comprises 63 patients with diagnosed vasculitis of the skin who had abnormal findings in the urine. Thirteen of these patients had positive skin findings and abnormal findings in the urine, with concomitant attacks of dyspnea as seen in bronchial asthma. These patients account for 20% of the entire group, while there was an incidence of 37% of systemic manifestations. Skin findings: 45% had a maculopapular rash, 36% had urticarial findings, 13% had urticaria and angioedema and 6% had angioedema alone. Nonspecific biologic syndrome of evolution was statistically significant while no significant changes were found in the number of white blood cells and eosinophils. The degree of proteinuria ranged from 0.1 g/L to 1.16 g/L. Most patients with proteinuria above 0.25 g/L had microhematuria. Slightly over 50% of the patients had signs of complement activation by the alternative pathway, along with the presence of cryoglobulins. Increased histamine in the serum was found in over 50% of the patients although the values of histamine did not correlate with the degree of proteinuria. Proteinuria was not detected in patients with very high values of histamine (and without signs of vasculitis), which indicates that histamine itself responsible for changes in the glomeruli. There is a possibility that local tissue hyperhistaminemia is responsible for the increased permeability of the basal membrane of the glomeruli. According to the obtained results, the etiology of proteinuria and microhematuria should be pursued in the pathogenesis of vasculitis as signs of complement activation indicate. Other possible causes for proteinuria were excluded. The proteinuria was selective, benign according to its course and degree, occurred concomitantly with skin findings and was absent during remission of the disease. PMID- 1916448 TI - [Laboratory study of patients with endemic nephropathy]. AB - The introduction deals with the main characteristics of two representatives of high risk pregnancies: diabetes mellitus and EPH gestoses. Particular interest was shown in risks that may occur in pregnant diabetics, with which they must be acquainted. Some theories are given on the pathogenesis of EPH gestoses. The aim of our investigation was to determine the concentration at which immunoglobulins G, M and A pass in cord blood, amniotic fluid and urine, and whether there is a significant difference between control group and among pregnant diabetics or those with EPH gestoses. The investigation was performed by the nephelometric technique on the Immunochemistry Analyzer. Each group consisted of 20 women, with a total of 60. Immunoglobulins A, M and G were determined in the mothers' sera, cord blood or amniotic fluid. IgG was obtained in urine in measurable concentrations. A significant increase of IgG was found in the urine of pregnant diabetics. IgM was significantly increased in the sera of diabetic mothers. IgA was significantly increased in pregnant diabetics, while both high risk pregnancy groups had an increased IgA in cord blood. The values of IgA in amniotic fluid were decreased in the EPH gestoses group in comparison to the group of diabetics. The authors find these variations interesting and feel they should be followed in other high risk pregnancy groups. PMID- 1916449 TI - [Levels of immunoglobulins in various media from healthy pregnant women and women with diabetes mellitus and EPH gestosis]. AB - The introduction deals with of the history, etiology and, briefly, clinical manifestations of endemic nephropathy. The authors state that a large number of investigations have been done until today, but without producing a diagnostic test for early diagnosis of the disease. This led the authors to pursue certain laboratory investigations. The control group consisted of 30 healthy individuals while patients diagnosed as Endemic Nephropathy were grouped according to stages of the disease: initial, developed, terminal stages. Nucleotides in erythrocytes (5' UMP, 5' IMP, 5' GMP, 5,CMP, 5' AMP, 5' ADP, 5' ATP) were determined on the Acidic Aminoanalyzer, with use of a special UV detector. Catecholamines in the urine were determined by using ratiofluorometery. Creatinine phosphocinase, hydroxybutirat--dehydrogenase and 2,3 DPG were determined on the "Carlbiochem" enzymometer. LDH, its isoenzymes as well as its profile were determined by electrophoresis on starch gel. Specific proteins such as haptoglobin, alpha 2 macroglobulin, alpha 1 antitrypsin, alpha 1 acid glycoprotein, properdin factor B, ceruloplasmin were determined on the Immunochemistry Analyzer. Total cholesterol and cholesterol in lipoproteins fractions VLDL, LDL and HDL were determined on the Cholesterol Analyzer. All results were evaluated statistically. Our conclusion is that they are interesting and contribute to the diagnosis of endemic nephropathy. PMID- 1916450 TI - [Specific hormone reactions to aircraft noise in pregnant women]. AB - In order to find out if there is some specific hormonal reaction to JET aircraft noise, a group of eight pregnant women, living in a small suburban community near the airport "Beograd", were investigated. Pregnant women in the first three months of pregnancy were exposed to the aircraft noise of 75-85 dB/A during 60 minutes, before and after that blood and urine samplers were taken for analyses. Those preliminary result of the level of cortisone, cortisol, testosterone and prolactin suggested that aircraft noise modified the hormonal reaction. Further investigation is needed in order to point out some other possibilities. PMID- 1916451 TI - [Immunologic disorders in lung malignancies and possibilities of immuno corrective therapy]. AB - The nonspecific immune competence was investigated in three groups of patients with bronchogenic lung cancer: group I (n = 30) was tested prior to any therapy; group II (n = 8) after radiotherapy; and group III (n = 13) after the end of combined radio and immunotherapeutical (Thymex-L) treatment. A total of 46 healthy persons served as control group. Both cellular (the number and function of T cells and mononuclear phagocytes) and humoral (the number of B cells and the levels of serum immunoglobulins and immune complexes) immune reactivity were tested. The number of T cells and B cells, as well as their function, were markedly depressed in a majority of patients before therapy; the number and reactivity of phagocytes were significantly higher in patients than in controls. The radiologic treatment caused further decrease of T cell number and function. The number of phagocytes was significantly higher than before radiotherapy. This treatment had no effect on the parameters of humoral immunity. All these parameters were less affected in patients who were simultaneously treated by irradiation and Thymex-L; no effect was seen on the humoral immunity, except the immune complexes, which returned to normal values only in that group of patients. PMID- 1916452 TI - [Parameters of humoral immunity in patients with breast carcinoma during therapy with leukocyte interferon]. AB - The values of parameters of humoral immunity, such as concentration of immunoglobulins IgG, IgA, and IgM, as well as the absorbance of patients serum at 450 nm (A4 5 0) in the presence of PEG 6000 (as a measure of the presence of immune complex in circulation, CIC) in a group of breast cancer patients stage T + N0 M0, after surgical tumor resection, and before and after various therapy phases with the leucocyte IFN therapy are given. The IFN (product of Torlak, Belgrade, or Immunological Department Zagreb) therapy was performed in four therapy phases. During the first month (first phase) 3.10(6) U IFN-alpha were administered i.m. every day, during the second month 3.10(6) U were administrated thrice weekly, during the third month 3.10(6) U IFN-alpha were administered i.m.twice weekly, and during the fourth month 3.10(6) U IFN were administered i.m. once a week. The average concentration of IgG, IgA, and IgM fall in the range of normal values during the therapy. Nevertheless, some mild stimulation of the IgG production and transient one for IgA can be noticed. The average value of A4 5 0 for patients was before therapy significantly (P less than 0.05) higher than normal value--at the end of the therapy it was in the range of normal A4 5 0. PMID- 1916453 TI - Reduced arterial baroreflex control of muscle sympathetic nerve activity in young borderline hypertensives. AB - Mean arterial pressure (MAP), heart interval (HI) and muscle sympathetic nerve activity (MSNA) were measured before and after a bolus injection of phenylephrine in 11 normotensives (NT) and 12 borderline hypertensives (BHT). (1) Basal MSNA was elevated in BHT compared to NT. (2) Both baroreflex slope for HI and that for MSNA were significantly less in BHT. (3) There was an inverse correlation between the slope for MSNA and the basal MSNA (r = -0.63). Thus, arterial baroreflex control of sympathetic activity may be reduced in BHT and the reduction may be involved in the elevated sympathetic nerve activity in these subjects. PMID- 1916454 TI - Local venous lactate changes and spectral analysis of surface EMG during fatiguing isometric efforts in intrinsic hand muscles. AB - In this study relationships between local venous lactate concentrations and power spectrum changes in surface EMG due to fatiguing isometric contractions were investigated. Two different isometric efforts of the opponents pollicis muscle, 25% and 50% of maximum voluntary contraction, were examined. In 25% of maximum voluntary contraction no changes in local venous lactate were observed, whereas mean power frequency values of surface EMG shifted significantly towards lower frequencies. On the contrary, in 50% of maximum voluntary contraction lactate significantly increased and was related to the mean power frequency shifts of the surface EMG. These data suggest that lactate plays a role in muscle fatigue only in a limited intensity range of isometric muscle contractions. PMID- 1916455 TI - Similarities in age differences in heat pain perception and thermal sensitivity. AB - Age differences in the thresholds for heat pain, warmth and cold were studied in 64 healthy persons from 17 to 63 years of age (32 women, 32 men). The stimuli were applied to the thenar and the dorsum pedis with a contact thermode. The thresholds increased significantly with age in all modalities on the foot, but not on the hand. Furthermore, the quotients of the individual foot and hand thresholds revealed a significant relative increase in all thresholds on the foot. The length of the afferent pathways seems to influence the degree of age related changes both in heat pain perception and in thermal sensitivity, resulting in a distal-proximal pattern of age-dependent decline. PMID- 1916457 TI - Focal reflex myoclonus in corticobasal degeneration. AB - Focal reflex myoclonus was observed in a patient clinically diagnosed as affected by corticobasal degeneration. Myoclonus was not preceded by a cortical discharge and contralateral parietal components of the somatosensory evoked potentials were reduced in amplitude. No simple pathophysiological mechanism can account for all cases of focal reflex myoclonus seen in clinical practice. PMID- 1916456 TI - Clinical observations in early and late onset Parkinson's disease. AB - The present study compares 30 patients who developed idiopathic Parkinson's disease (PD) at the age of 48 years or younger and 47 patients who developed the disease at the age of 68 years or older. PD patients with early onset had rigidity and bradykinesia as the predominant features at onset and during the course of the illness. In contrast older onset patients exhibited more often tremor at the beginning while later in the course most of them developed the full triad of symptoms i.e. tremor-rigidity-bradykinesia. In spite of such differences the overall disability status did not differ between the two groups of patients. An additional observation was that the early onset patients were apter to show earlier and more often abnormal movements and response fluctuations related to the L-Dopa therapy. PMID- 1916458 TI - Familial occurrence of hypothyroidism and cerebellar ataxia. AB - Several cases of association between cerebellar ataxia and hypothyroidism have been reported, in which cerebellar symptoms regressed after euthyroid state was obtained, suggesting an etiologic relationship between hypothyroidism and ataxia. We present a further case of hypothyroidism and ataxia, with a peculiar positive family history for both thyroid and cerebellar disorders. Long-term replacement therapy with L-thyroxine determined the regression of hypothyroidism; however, no improvement in cerebellar symptoms was observed. The lack of response of the neurologic symptoms to L-thyroxine treatment suggests the absence of an etiological relationship between thyroid disease and cerebellar disease in this case. PMID- 1916459 TI - Unexpected white matter changes in an early treated PKU case and improvement after dietary treatment. AB - We report a case of classic phenylketonuria (PKU) treated by dietary restriction until the age of 5 years. At the age of 18 years, she developed anxious depressive symptoms and deterioration of school performance. Neurophysiological investigations showed changes in VEPs and BAEPs and brain MRI showed white matter abnormalities. The return to a diet low in phenylalanine reduced psychiatric disturbances and reversed neurophysiological and MRI changes. Our data confirm previous observations of white matter involvement in PKU and the utility of lifelong dietary therapy to prevent neurological and/or psychiatric deterioration. PMID- 1916460 TI - Hemorrhagic cerebral infarct and ulcerative colitis. A case report. AB - We report the occurrence of a cerebral ischemic infarct in a young normotensive woman suffering from ulcerative colitis. One week later, clinical neurological deterioration corresponded with hemorrhagic transformation of the previously ischemic region and white matter edema. Extensive laboratory investigation excluded other possible causes for stroke mechanism and rather supported a cerebral vasculitic process, while significant improvement both on neurological and bowel function was observed under prednisone therapy. This report provides some additional support to the possible association between ulcerative colitis and cerebrovascular complications. PMID- 1916461 TI - Cervicogenic headache. The differentiation from common migraine. An overview. AB - Common migraine and cervicogenic headache have many traits in common, so many that they may be mixed up. Both are unilateral headaches with a female preponderance. However, as for a number of variables, they differ. This first and foremost has to do with factors concerning the neck. In cervicogenic headache, the following symptoms and signs are present: a reduced range of motion in the neck; mechanical precipitation of attack, either by neck movements or by external pressure over the greater occipital nerve of the C2 root; ipsilateral shoulder/arm pain; unilaterality without side-shift. Similar findings are usually not made in common migraine. Typical migraine symptoms, such as nausea, vomiting, photophobia, and phonophobia also occur in cervicogenic headache, but less frequently and to a lesser degree. Operative procedures directed to occipital/nuchal structures may afford decisive differentiation between the two disorders. In our estimation, cervicogenic headache and common migraine are two distinct disorders, with their own clinical patterns, pathogenesis, treatment - and, in all probability, also prognosis. PMID- 1916462 TI - Advances in neoplastic disease of the liver and biliary tract. PMID- 1916464 TI - Liver disease in infancy: a 20 year perspective. PMID- 1916463 TI - Cystic disease of the liver and biliary tract. AB - The widespread availability of ultrasound imaging has led to more frequent recognition of cystic disease affecting the liver and biliary tract. There is a wide range of possible causes. Cystic disease of infective origin is usually caused by an Echinococcal species, or as the sequel of a treated amoebic or pyogenic abscess. The clinical and radiological features are often then distinctive and will not be dwelt upon in this review, except in respect of their contribution to the differential diagnosis of non-infective disorders. The principal non-infective cysts can be conveniently divided between the simple cyst, the polycystic syndromes (usually with coexistent renal disease), Caroli's syndrome, and choledochal cysts. The overlap between constituent members of these groups, and the association of cystic disease with hepatic fibrosis (especially with congenital hepatic fibrosis) has attracted considerable attention, and it has been suggested that they may all be considered to belong to a hepatobiliary fibrocystic continuum. In addition there are a variety of cystic neoplasms and a miscellany of unusual forms. PMID- 1916465 TI - Portal hypertension--25 years of progress. PMID- 1916466 TI - Infections. PMID- 1916467 TI - Nutritional support in liver disease. PMID- 1916469 TI - Immunological aspects of liver disease. PMID- 1916468 TI - Drug metabolism and hepatotoxicity. PMID- 1916472 TI - The Liver Unit at King's College. PMID- 1916473 TI - Primary biliary cirrhosis. PMID- 1916471 TI - Chronic active hepatitis. PMID- 1916475 TI - History and development of the Liver Unit. PMID- 1916470 TI - Viral hepatitis. PMID- 1916474 TI - Liver transplantation. PMID- 1916476 TI - Acute liver failure. PMID- 1916477 TI - Liver regeneration in relationship to acute liver failure. PMID- 1916478 TI - Alcoholic liver disease. PMID- 1916479 TI - Idiopathic bile acid malabsorption--a review of clinical presentation, diagnosis, and response to treatment. AB - Between 1982 and 1989, the seven day retention of 75SeHCAT was measured in 181 patients with chronic diarrhoea that remained unexplained after full investigation. Altogether 121 of the 181 had a seven day 75SeHCAT retention greater than or equal to 15% and thus had no evidence of abnormal bile acid turnover. Twenty one had a seven day 75SeHCAT retention greater than or equal to 10% but less than 15%. Their clinical features were typical of the irritable bowel syndrome, and none of eight treated with cholestyramine showed symptomatic improvement. Sixteen patients had a seven day retention greater than or equal to 5% and less than 10%, six of whom had improved symptoms after treatment with bile acid chelating agents. The remaining 23 patients had a 75SeHCAT retention of less than 5% at seven days and responded to bile acid chelators. This group had a characteristic illness with intermittent watery diarrhoea, but no constitutional upset. It was not possible to distinguish the patients with bile acid malabsorption exclusively on the basis of the clinical symptoms and investigations, other than 75SeHCAT retention. We conclude that the measurement of 75SeHCAT retention is useful, appropriate, and necessary in patients with unexplained chronic diarrhoea. PMID- 1916480 TI - Effect of protein and lactulose on the production of gamma-aminobutyric acid by faecal Escherichia coli. AB - The value of lactulose treatment in hepatic encephalopathy is widely recognised but its mode of action remains controversial. Much evidence supports a role for gamma-aminobutyric acid in hepatic encephalopathy, and lactulose could alter its bacterial production in the gut. Using the rat synaptic membrane assay and gas chromatography mass spectrometry, the production of gamma-aminobutyric acid by faecal Escherichia coli, with and without the addition of albumin, haemoglobin, whole blood, and lactulose under aerobic and anaerobic conditions was determined. Using an inorganic medium, maximal gamma-aminobutyric acid production occurred after a culture period of between 25 and 50 hours. The concentration after 30 hours of aerobic culture at 37 degrees C by a single strain was mean (SEM), 101 (5) mumol/l (99% confidence intervals 87-114 mumol/l; n = 8; interassay coefficient of variation 14.7%). gamma-aminobutyric acid production was significantly increased by the addition of albumin and haemoglobin. Under anerobic conditions, it was one fifth of that produced aerobically, but the addition of albumin and haemoglobin increased production by greater than 700%. Lactulose did not significantly attenuate gamma-aminobutyric acid production under aerobic or anaerobic conditions. gamma-aminobutyric acid determined by the rat synaptic membrane assay showed a highly significant correlation (r = 0.99) with that detected by gas chromatography mass spectrometry. These data confirm that gamma-aminobutyric acid is produced by faecal E coli and that protein enhances its production considerably, and suggest that lactulose does not exert its therapeutic effect by attenuating gamma-aminobutyric acid production. PMID- 1916481 TI - Deoxyribonucleic acid amplification and hybridisation in Crohn's disease using a chlamydial plasmid probe. AB - The possibility that Crohn's disease is caused by infection with Chlamydia trachomatis was examined by probing for chlamydial plasmid deoxyribonucleic acid (DNA) in DNA extracts from Crohn's disease tissue and by means of a serological study. Gut DNA extracts were obtained from 10 patients with Crohn's disease and four control subjects and were probed with a chlamydial plasmid probe after Southern blotting. The polymerase chain reaction was also used to amplify any chlamydial plasmid DNA present in tissue DNA extracts, before Southern blotting and probing. Chlamydial proctitis control specimens were not available: gut DNA extracts mixed with traces of chlamydia plasmid served as positive controls. Using these techniques, no chlamydial plasmid DNA sequences were found in Crohn's disease tissue. An enzyme linked immunosorbent assay for C trachomatis LI was performed on 48 patients with Crohn's disease and 48 control subjects. Seropositivity was present in 14.6% of patients and 29% of control subjects and was not statistically significant (p greater than 0.05). The failure to show chlamydial DNA and the lack of serological response to chlamydia make C trachomatis infection a very unlikely factor in the pathogenesis of Crohn's disease. PMID- 1916482 TI - Smoking, humoral immunity, and ulcerative colitis. AB - Since ulcerative colitis predominantly affects non-smokers and ex-smokers we have examined the possibility that smoking modifies the humoral immune response to an antigenic challenge from the gut lumen. Gut lavage was used in healthy subjects and patients with ulcerative colitis, including both smokers and non-smokers. Antibodies in the intestinal fluid to Escherichia coli (five pooled serotypes), Candida albicans, gliadin, ovalbumin, and beta lactoglobulin were measured by ELISA to determine specific antibody concentrations of IgG, IgA, and IgM classes. Total IgG, IgA, and IgM were also measured in intestinal secretions and serum. In addition, circulating antibody concentrations of IgG, IgA, and IgM to three gut commensals - E coli (five pooled serotypes) C albicans, and Poroteus mirabilis were measured. There was a significant reduction in the IgA concentration in intestinal fluid of smokers with ulcerative colitis compared with healthy non smoking controls. No other significant differences were found between the groups. Overall, these data are not consistent with the idea that smoking suppresses immune responses in the gut and suggest that the effect of smoking in colitis is mediated by another mechanism. PMID- 1916483 TI - Diversion colitis: histological features in the colon and rectum after defunctioning colostomy. AB - Diversion of the faecal stream by ileostomy or colostomy leads to inflammation in the defunctioned segment, known as diversion colitis. The affected bowel is rapidly restored to normality by reanastomosis. Diversion colitis should not be mistaken for inflammatory bowel disease, for which reanastomosis would be inappropriate. Studies of biopsy material from patients with diversion colitis have shown a variety of histological features, but no consistent pattern. The histology in resection specimens of defunctioned large bowel from 15 patients with no pre-existing inflammatory bowel disease was studied. Nine patients had symptoms of abdominal pain or rectal discharge of blood or mucus that developed between 9 months and 17 years after diversion procedure. The histology was abnormal in all. Findings were similar in 14 patients, regardless of the duration of faecal diversion, and comprised diffuse mild chronic inflammation with or without mild crypt architectural abnormalities, crypt abscesses, or follicular lymphoid hyperplasia. One patient had more severe changes, resembling active ulcerative colitis. These features in biopsy specimens are unlikely to be diagnostic but should provide useful information in avoiding a mistaken diagnosis of inflammatory bowel disease in these patients. PMID- 1916484 TI - Inflammatory bowel disease in the Bedouin Arabs of southern Israel: rarity of diagnosis and clinical features. AB - A prospective epidemiological and clinical study of ulcerative colitis and Crohn's disease was undertaken in the Bedouin Arabs of southern Israel between 1981 and 1990. There were six patients with ulcerative colitis and the prevalence rate in 1990 was calculated to be 9.8/10(5) (95% confidence intervals 3.6-17.4) in the total population, or 6.2/10(5) (0.8-22.5) in men and 13.7/10(5) (3.7-35.0) in women. Two cases of Crohn's disease occurred, both in women; the prevalence rate was 3.2/10(5) (0.4-11.8) in the entire population, and 6.8/10(5) (0.8-17.5) in women. The prevalence rates (age adjusted) in Arabs were significantly lower (p less than 0.01) than the corresponding rates in the local Jewish populations. The Bedouin patients were aged mean (SD) 34.0 (16.4) years at time of diagnosis. The clinical features of both diseases resembled those in the Jewish and other reported populations. It is suggested that the exposure of the Bedouin Arabs to the environmental causative factors of ulcerative colitis and Crohn's disease has hitherto been limited and thereby accounts for the rarity of these diseases in this population. PMID- 1916485 TI - Validation of organ culture in colonic adaptation to surgical manipulation. AB - Valuable information on intestinal adaptation can be gained by using the technique of organ culture to measure the crypt cell production rate. It is not known, however, whether the production rate in organ culture accurately represent that in vivo. Colonic crypt cell production rate, determined by a standard method in vivo, was compared with that in vitro in organ culture in 56 rats. Extensive jejunoileal bypass was used to stimulate colonic hyperplasia, and colonic defunction (by transverse colostomy) led to hypoplasia. There were no differences in crypt cell production rates between in vivo and in vitro groups in normal colon (4.62 (0.39) v 4.80 (0.23) cells/crypt/hour), after 80% jejuno-ileal bypass (7.81 (0.71) v 6.75 (0.72) cells/crypt/hour), or after defunction (2.11 (0.39) v 1.81 (0.35) cells/crypt/hour). Adapting colonic mucosa does not undergo appreciable readaptation in vitro in short term organ culture (10-24 hours). Crypt cell production rate results obtained in man probably reflect in vivo values. PMID- 1916486 TI - Relation between electromyography and anal manometry of the external anal sphincter. AB - Thirteen patients with faecal incontinence and 26 control subjects were studied to investigate whether a quantitative electromyographic (EMG) signal could be correlated to anal manometry. Three different electrodes were used--a concentric needle electrode, a disposable sponge electrode, and a hard anal plug electrode. The maximum amplitude of the EMG recording was used as a quantitative parameter. Linear regression showed significant correlation between EMG and anal manometry with the sponge electrode, both at rest and during squeeze. Significant correlation was also found with the concentric needle electrode during squeeze but not at rest. No correlation was found with the hard anal plug electrode either during squeeze or at rest. Reproducibility studies using the sponge electrode showed acceptable day to day variation. In conclusion, quantitative EMG recordings from a disposable sponge electrode placed in the anal canal correlate well to anal manometry and may be used for assessment of sphincter function, but the hard anal plug electrode cannot be recommended. PMID- 1916487 TI - Failure of cholinergic stimulation to induce a secretory response from the rectal mucosa in cystic fibrosis. AB - The secretory response to cholinergic stimulation was investigated in rectal biopsy specimens from children with cystic fibrosis and a control group using a modified Ussing chamber technique. Acetylcholine (10(-3) mol/l) increased the short circuit current in 12 control specimens by mean (SEM) 83.0 (16.4) microA/cm2, but samples from five children with cystic fibrosis failed to exhibit such a response (-1.4 (3.2) microA/cm2). Amiloride (10(-4) mol/l), which will inhibit electrogenic sodium absorption in viable tissues, caused similar reductions in the short circuit current of both control and cystic fibrosis tissues (control = -37.7 (7.7) microA/cm2; cystic fibrosis = -44.0 (9.3) microA/cm2). Thus, the failure of chloride secretion observed in the small intestine also exists in the rectal mucosa. This observation could be used both to aid diagnosis and to study the basic defect. PMID- 1916488 TI - A 10 year single centre experience of percutaneous and endoscopic extraction of bile duct stones with T tube in situ. AB - A non-randomised single centre study of 226 consecutive patients referred over 10 years with retained common bile duct stones and a T tube in situ or a cholecystostomy tube are reported. Percutaneous extraction was attempted in 204 and endoscopic extraction in 68 patients. Percutaneous clearance was achieved in 158 (77.5%) patients and endoscopic clearance in 52 (76.5%) patients. Six of 153 (3.9%) patients followed after percutaneous treatment suffered major complications (pancreatitis, cholangitis, or tract perforation). Three of 67 (44%) patients followed after endoscopic treatment suffered major complications (pancreatitis, cholangitis, or bleeding). When the initial method of treatment failed, the alternative was used, resulting in an overall success rate of bile duct clearance of 94.3%. It is concluded that percutaneous and endoscopic methods of bile duct clearance in patients with a T tube in situ are equally effective, carrying similar complication rates. This study has helped to clarify the indications and efficacy of these alternative treatments. PMID- 1916489 TI - Effect of ursodeoxycholic acid treatment on ileal absorption of bile acids in man as determined by the SeHCAT test. AB - The effects of urodeoxycholic acid on ileal absorption of bile acids and on serum bile acid and lipoprotein concentrations were studied. Eight healthy subjects were investigated. The gamma emitting bile acid analogue, SeHCAT, was given orally and its fractional catabolic rate and seven day retention were assessed by repeated external counting over the upper abdomen during the next seven days. Ursodeoxycholic acid was then given orally at a dose of 15 mg/kg/day for three weeks and the study was repeated during treatment. The fractional catabolic rate increased by 64% (mean (SD), 0.333 (0.159) v 0.203 (0.061)/day; p less than 0.05) and seven day retention decreased by 44% (15(10) v 27(10)%, p less than 0.001), indicating bile acid malabsorption. Total serum cholesterol fell from 5.79 (1.22) to 5.50 (1.18) mmol/l (p = 0.05), while serum ursodeoxycholic acid increased 22 fold (7.87 (2.67) v 0.34 (0.24) mumol/l, p less than 0.001). Five of the subjects continued taking 30 mg/kg/day of ursodeoxycholic acid for one week and showed an increase in fractional catabolic rate of 81% (0.300 (0.091) v 0.166 (0.037)/day; p less than 0.05) and a fall in seven day retention of 50% (16 (12) v 32 (8)%, p less than 0.01). There were significant reductions in total cholesterol (5.36 (1.71) v 6.08 (1.47) mmol/l; p less than 0.05) and low density lipoprotein cholesterol (3.70 (1.33) v 4.58 (1.16) mmol/l; p less than 0.05). The results support the concept tht ursodeoxycholic acid treatment interferes with the absorption of endogenous bile acids, and emphasise the beneficial effects of this treatment of lipoprotein concentrations in man. PMID- 1916490 TI - Inhibitory effect of a cholecystokinin antagonist on the proliferative response of the pancreas to pancreatobiliary diversion. AB - Since pancreatobiliary diversion probably stimulates pancreatic growth by increasing cholecystokinin secretion, the effect of the cholecystokinin antagonist CR-1409 on this adaptive response was tested. Male Wistar rats (n = 108) weighing 220-250g were randomised to receive either pancreatobiliary diversion (n = 60) or sham diversion (n = 48) and thereafter to receive either saline injections or CR-1409 (10 mg/kg/day, subcutaneously). Rats were killed at four, seven, and 14 days postoperatively, when blood was obtained for cholecystokinin assay and the pancreas was assessed for proliferative activity by three techniques: nucleic acid and protein assay, bromodeoxyuridine labelling, and metaphase arrest after vincristine administration (1 mg/kg, intraperitoneally). Pancreatobiliary diversion increased plasma cholecystokinin concentrations by 91% at seven days and 137% at 14 days, irrespective of CR-1409 treatment. Total pancreatic RNA content was doubled by pancreatobiliary diversion at four days (2.15 v 1.07 mg/100 g body weight: p less than 0.001) and at seven days (3.43 v 1.76 mg/100 g: p less than 0.001), and trebled at 14 days (4.27 v 1.32 mg/100 g: p less than 0.001). Pancreatobiliary diversion increased bromodeoxyuridine labelling index from 1.1 to 3.7% at seven days and the cell birth rate from 0.09 to 0.06%. CR-1409 completely abolished this proliferative response and partly prevented the rise in RNA. The results confirm pancreatic hypertrophy and increased acinar cell proliferation after pancreatobiliary diversion. CR-1409 prevents this adaptive growth, probably by blocking cholecystokinin receptors. Bromodeoxyuridine labelling and the metaphase arrest technique may be used to assess pancreatic cell kinetics. PMID- 1916491 TI - Cereal chemistry, molecular biology, and toxicity in coeliac disease. PMID- 1916492 TI - Ursodeoxycholic acid in chronic liver disease. AB - The hydrophilic bile acid ursodeoxycholic acid has recently been shown to reduce biochemical markers of both cholestasis and hepatocellular damage in patients with chronic liver diseases. The most compelling evidence available is for chronic cholestatic liver diseases, in particular primary biliary cirrhosis, primary sclerosing cholangitis, and cholestasis associated with cystic fibrosis. The effects may be less beneficial in patients with advanced liver disease from these conditions. Data from placebo controlled trials are now available in support of earlier uncontrolled observations, but it is not yet clear whether short term benefit results in an improvement in longterm prognosis. The mechanism of action of the compound seems to reside in its displacement of toxic hydrophobic bile acids from both the bile acid pool and hepatocellular membranes. There may be an independent effect on bile flow, which could be of particular importance in cystic fibrosis, and possibly an effect on the immune system. Ursodeoxycholic acid should now be regarded as occupying a central place in the medical management of chronic cholestatic liver diseases, in particular primary biliary cirrhosis, because it improves cholestasis and reduces hepatocellular damage and it is not toxic. Research should now be targeted on whether treatment with ursodeoxycholic acid, initiated early in cholestatic liver conditions, improves the long-term outcome. PMID- 1916493 TI - Appropriateness of cholecystectomy in the United Kingdom--a consensus panel approach. AB - A consensus development approach was used to assess the extent to which doctors in the UK agreed about the appropriate indications for cholecystectomy. Two panels, one composed entirely of surgeons and one containing a mix of relevant specialists, were asked to rate a series of possible indications. A consensus was achieved for 61% (surgical panel) and 67% (mixed panel) of indications considered. The surgical panel considered more indications as being appropriate for cholecystectomy (29% v 13%) and fewer indications as being inappropriate (27% v 50%) than the mixed panel. For between one third and a half of all indications, the panels were unable to reach agreement, partly as a result of differences in views as to the role of endoscopic sphincterotomy. PMID- 1916494 TI - Double blind, placebo controlled trial of metronidazole in Crohn's disease. AB - A double blind study compared the efficacy of metronidazole in two doses (20 mg/kg, 10 mg/kg) with placebo in patients with Crohn's disease. One hundred and five patients participated but only 56 completed the 16 week study -21 were withdrawn for deterioration of symptoms, 17 for adverse experiences, and 11 for protocol violation. Significant improvement in disease activity as measured by the Crohn's disease activity index (metronidazole 20 mg/kg, 97 units; metronidazole 10 mg/kg, 67 units; placebo -1 unit, p = 0.002) and serum orosomucoid (metronidazole 20 mg/kg/day, 49; 10 mg/kg/day, 38; placebo, -9, p = 0.001)) were detected. Changes in C reactive protein concentrations did not achieve significance when all three groups were considered but were significant when all metronidazole treated patients were grouped and compared with the placebo treated patients (0.8 v -0.9, p less than 0.05). Although patients receiving metronidazole 20 mg/kg/day had a greater improvement in disease activity than those receiving 10 mg/kg/day (difference 30 units (95% confidence intervals -27-87), the small sample size may have precluded the detection of statistical significance. Preliminary analysis suggests that metronidazole was more effective in patients with disease confined to the large intestine or affecting both small and large bowel than in those with small bowel disease only. There were no differences in remission rates between metronidazole and placebo treated patients. We conclude that metronidazole warrants further assessment in the treatment of patients with active Crohn's disease. PMID- 1916495 TI - Self-dilatation of oesophageal strictures. AB - A new technique for the management of upper and mid-oesophageal benign strictures is reported. A deflated oesophageal balloon catheter coated with steroid paste is passed by the patient through the stricture, the balloon is inflated and then withdrawn. This technique can be used for both strictures caused by tablet or corrosive damage that recur rapidly and where stricturing is the result of a chronic disease not amenable to medical or surgical treatments. Three patients in who this technique has been used with satisfactory patient tolerance and compliance and good relief of symptoms are reported. PMID- 1916496 TI - Elemental diet in the management of Crohn's disease during pregnancy. AB - Four patients with Crohn's disease were treated with an elemental diet during pregnancy. Two had active disease and two also had symptoms of small intestinal obstruction. All went into a clinical remission within a few days of starting treatment. Treatment periods varied from two to four weeks, and were followed by elemental diet as a supplement to normal food in two patients. At term, all delivered a healthy infant. These patients indicate that elemental diet is a safe form of treatment for Crohn's disease during pregnancy and may be considered as an alternative to conventional drug treatments which carry a theoretical risk of teratogenesis. PMID- 1916497 TI - Transplantation of a donor liver with haemochromatosis: evidence against an inherited intrahepatic defect. AB - An iron loaded liver from a 40 year old man with occult haemochromatosis was transplanted into a 19 year old woman with acute liver failure secondary to a paracetamol overdose. Increased parenchymal hepatic iron was found in a liver specimen at biopsy undertaken because of mild rejection 30 days after transplantation. After transplantation the patient had two episodes of liver rejection confirmed by biopsy. The hepatic iron concentration fell from 161 mumol/g on day 30 after transplant to 26.5 mumol/g (normal less than 40) on day 210. Iron absorption, measured 45 days after transplant, was in the normal range at 12.4%. The rapid fall in hepatic iron and the normal iron absorption study result suggest that the genetic defect of haemochromatosis is not exclusively an intrahepatic defect. PMID- 1916498 TI - Gastrointestinal intraluminal pH. PMID- 1916499 TI - Incidence of heterotopic gastric mucosa in the upper oesophagus. AB - In a prospective study of the frequency and clinical importance of heterotopic gastric mucosa in the upper oesophagus, 634 consecutive veteran patients (98% male), undergoing endoscopy for various gastrointestinal complaints, were evaluated. Sixty four patients (10%) had heterotopic gastric mucosal patches varying in size from 0.2-0.3 cm to 3 x 4-5 cm often immediately below the upper oesophageal sphincter. Biopsies of these patches showed fundic type gastric mucosa with chief and parietal cells. The 10% prevalence is more than twice the highest reported prevalence rate of endoscopically detected patches in the upper oesophagus. The characteristic location of these patches at the sphincter area, their uniformly fundic type gastric mucosa, and their poor correlation with clinical and endoscopic evidence of gastro-oesophageal reflux support the hypothesis that they are congenital in nature. PMID- 1916500 TI - Detection of Helicobacter pylori infection of the gastric mucosa by measurement of gastric aspirate ammonium and urea concentrations. AB - Helicobacter pylori possesses unusually high urease activity that lowers the urea concentration and raises the ammonium concentration of the gastric juice in infected people. The value of measuring urea and ammonium concentrations in gastric juice obtained during upper gastrointestinal endoscopy as a means of diagnosing the presence and eradication of the infection was assessed. Twenty four subjects with the infection and 14 in whom it had been eradicated were examined. Their H pylori status was confirmed by antral biopsy and 14C urea breath test. The median (range) gastric juice urea concentration in infected subjects was 0.8 mmol/l (0.5-2.9 mmol/l), which was lower than that in the uninfected subjects (2.1 mmol/l (1.0-3.7 mmol/l)) (p less than 0.001). The median gastric juice ammonium concentration in infected subjects was 3.4 mmol/l (1.0 13.0 mmol/l), which was higher than that in the uninfected subjects (0.64 mmol/l (0.02-1.4 mmol/l)) (p less than 0.001). Though the two groups overlapped in respect of their urea and ammonium concentrations, they were completely different when the urea: ammonium ratios were calculated--the ratios ranged from 0.04-0.7 (median 0.26) and from 1.1-113 (median 3.4) in infected and uninfected subjects respectively (p less than 0.001). Treatment with H2 antagonists did not change the concentrations of urea and ammonium or their ratio in gastric juice. Measurement of the urea: ammonium ratio in aspirated gastric juice obtained during routine upper gastrointestinal endoscopy may provide a rapid method of detecting H pylori infection and of confirming its eradication. PMID- 1916502 TI - Physical activity at work and duodenal ulcer risk. AB - To determine whether the social class differences in duodenal ulcer frequency may be explained by differences in physical activity at work, the energy expenditure during work, smoking habits, and social class were compared in 76 recently diagnosed duodenal ulcer patients and in age and sex matched community controls. As anticipated, the relative risk of duodenal ulcer showed significant associations with smoking and social class. Social class and physical activity at work were associated with one another. After adjusting for age, sex, smoking, and social class, physically active work was still associated with duodenal ulcer, with relative risks for moderate and high activity compared with sedentary work being 1.3 (0.6-3.0) and 3.6 (1.3-7.8) respectively. Within each social class stratum, the relative risk of having a duodenal ulcer was greater in those with a high level of occupational activity than in those undertaking sedentary work. PMID- 1916501 TI - Weekend treatment with 20 and 40 mg omeprazole: effect on intragastric pH, fasting and postprandial serum gastrin, and serum pepsinogens. AB - Weekend treatment with 20 mg omeprazole reduces ulcer relapse rates but the results may improve with a higher dose regimen. We have evaluated three day weekend treatment with 20 and 40 mg doses of omeprazole in eight healthy subjects in a double blind crossover study. Twenty four hour ambulatory intragastric pH and basal and meal stimulated serum gastrin and serum pepsinogens A and C values were studied. The investigations began on the Friday before the third weekend course of omeprazole and were repeated on alternate days, except Sundays, for two weeks. When compared with values before the study, median 24 hour intragastric pH and basal and meal stimulated gastrin concentrations were significantly (p less than 0.01-0.05), but transiently, raised with both doses of omeprazole. Basal pepsinogen A and C values were significantly (p less than 0.01) increased on all study days, but did not return to their pre-study values before the next weekend dose, except for pepsinogen C in subjects treated with 20 mg omeprazole. A dose dependent effect was found for all parameters studied (p less than 0.05). In conclusion, weekend treatment with 20 and 40 mg omeprazole produces pronounced and dose dependent increases in intragastric pH, basal and meal stimulated serum gastrin, and basal serum pepsinogen A and C without inducing prolonged hypoacidity or hypergastrinaemia. Weekend treatment with 40 mg omeprazole merits further study in the prevention of peptic ulcer relapse. PMID- 1916503 TI - Acute upper gastrointestinal bleeding in patients with AIDS: a relatively uncommon condition associated with reduced survival. AB - To determine the cumulative incidence of acute upper gastrointestinal bleeding and its effect upon survival in patients with AIDS, 453 consecutive AIDS patients diagnosed in our hospital between June 1985 and March 1989 were followed for a median period of six months (maximum 42 months). The cumulative probability of acute gastrointestinal bleeding was 3% at six months and 6% at 14 months. This event was associated with significantly reduced survival. Independent risk factors for bleeding were: severe thrombocytopenia at the time of diagnosis and non-Hodgkin's lymphoma as the first clinical manifestation of AIDS. The potential causes of bleeding were investigated in all cases by emergency endoscopy or by necropsy examination in those patients whose clinical condition precluded the procedure. In nine of 15 patients, bleeding was due to lesions specifically associated with AIDS, but in the remainder the source of bleeding was not a direct consequence of HIV infection. We conclude that acute upper gastrointestinal bleeding rarely complicates the course of AIDS, but its occurrence is associated with decreased survival. As many of the causes are potentially treatable, a complete diagnostic approach is indicated in these patients, except those who are terminally ill. PMID- 1916504 TI - Trophic action of epidermal growth factor on human duodenal mucosa cultured in vitro. AB - The action of epidermal growth factor on the human duodenal mucosa has been studied by estimating the crypt cell production rate in cultured explants, using a stathmokinetic technique with crypt microdissection. The addition of epidermal growth factor (400 ng/ml) to paired explants from five patients caused an almost fivefold increase in the crypt cell production rate, showing that epidermal growth factor has a trophic action on the human duodenal mucosa in vitro. PMID- 1916505 TI - Placental ferritin in coeliac disease: relation to clinical stage, origin, and possible role in the pathogenesis of malignancy. AB - Placental ferritin is a tumour associated antigen present in the serum of patients with active Hodgkin's and non-Hodgkin's lymphoma, and the serum values fall during remission of the disease. There is no correlation between placental and total blood ferritin values. Because of the strong association between coeliac disease and lymphoma, 19 children with active and 25 with inactive coeliac disease were screened for the presence of placental ferritin. Thirty two children with other intestinal disorders served as controls. Placental ferritin was identified by using a monoclonal antibody in an ELISA procedure. The mean (SEM) placental ferritin value in the control serum was 12.6 (2.4) while the values in serum of patients with active and inactive coeliac disease were 117 (22.8) and 43.8 (10.2) U/ml respectively. Patients with active coeliac disease differed significantly from both control subjects (p = 0.0004) and those with inactive disease (p = 0.03). Peripheral blood lymphocytes contained no placental ferritin. It was present, however, in lamina propria lymphocytes of intestinal biopsy specimens from active coeliacs. Placental ferritin was also found in some of the better differentiated malignant cells in two patients with adult onset enteropathy associated lymphoma. Placental ferritin is known to have an immunosuppressive effect, and this may be one of the necessary steps in the development of malignancy associated with coeliac disease. Gluten free diet, by reversing this state, may have a role in the prevention of lymphoma. PMID- 1916506 TI - Improved prognosis of ovarian cancer in The Netherlands during the period 1975 1985: a registry-based study. AB - Survival of 568 patients with ovarian cancer, diagnosed in 1975-1985, was studied by means of a population-based registry in the Southeast Netherlands. Patients diagnosed in the period 1981-1985 had a significantly better prognosis than patients diagnosed in 1975-1980. This improvement of survival declined with advancing age of the patients. In women younger than 60 years, mortality from ovarian cancer decreased, while incidence remained stable. Apart from the effect of new treatment methods, consisting of more extensive tumor reduction and cisplatin-based combination chemotherapy, advances in supportive care as well as a trend toward earlier diagnosis, possibly in combination with an increasing proportion of less malignant tumors, may explain the improvement in prognosis. Survival was strongly related to stage at diagnosis and to age, the prognosis of younger patients being more favorable. Patients with tumors of either germ cell or stromal origin generally survived longer than patients with epithelial tumors, but this difference disappeared after adjustment for stage and age. Patients still alive after 6 years did not have a survival significantly different from that of the general female population. PMID- 1916507 TI - Endodermal sinus tumor of the ovary: a case series with flow cytometric DNA content analysis. AB - Endodermal sinus tumors (EST) are rare germ cell ovarian malignancies occurring primarily in young women. A retrospective review of the Magee-Womens Hospital tumor registry revealed eight cases of pure EST and two mixed tumors in which the EST component was predominant. Mean patient age was 18.2 years. Abdominal pain was the most common presenting symptom and a pelvic mass was palpable in all patients. Four patients are currently alive and well with no evidence of disease. All were treated with surgery and combination chemotherapy. Flow cytometric DNA content analysis of paraffin-embedded tumor tissue identified similar aneuploid cell populations in three of five tumors analyzed with relative peak positions of 1.72, 1.62, and 1.70. The management of women with endodermal sinus tumor remains controversial with regard to type of chemotherapy employed and the use of second look laparotomy. The prognosis role of flow cytometric DNA content analysis is yet to be determined. PMID- 1916508 TI - Antitumor effects of human recombinant interferon-gamma and tumor necrosis factor on five cervical adenocarcinoma cell lines, in vivo and in vitro. AB - We examined the antitumor effects of recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) on cervical adenocarcinoma cell lines, in vitro and in vivo. Four of five cell lines showed a high sensitivity to IFN-gamma, in vitro. One of five cell lines showed a remarkable sensitivity to TNF, in vitro. Only one cell line resistant to both IFN and TNF was derived from a well differentiated adenocarcinoma of endocervical type. Experiments using nude mice bearing transplanted tumors revealed that these cytokines were also effective against tumors in vivo. All these observations suggest that IFN-gamma or TNF can have positive effects in the treatment of patients with adenocarcinoma of the uterine cervix. PMID- 1916509 TI - Aggressive multimodality treatment for cervical cancer with paraaortic lymph node metastases. AB - A Phase I/II trial of weekly cisplatin and extended field radiation therapy for cervical carcinoma and paraaortic metastases was initiated. A total of 13 patients have entered this trial since 1985. The objective of the study was to determine the efficacy and toxicity of extended field radiation therapy and cisplatin as a radiation sensitizer in this high-risk group of patients. The addition of paraaortic nodal radiation was derived from our earlier trial using cisplatin and pelvic radiation therapy followed by combination chemotherapy (cisplatin, adriamycin and cytoxan). Of the 13 patients entered, 8 are alive without evidence of disease and 5 have recurred, all exclusively outside the treatment fields. Three of the five had positive scalene node biopsies prior to the initiation of therapy. Four patients have died from distant metastases, one is alive with lung and bone metastases, and there have been no recurrences in the pelvis or paraaortic treated areas. The encouraging results of complete local and pelvic control of tumor and acceptable toxicity warrants continuation of this trial. PMID- 1916510 TI - Presentation of cervical cancer. AB - To determine how patients with invasive cervical cancer present and whether presentation affects disease-free survival (DFS), a review of 81 patients treated for cervical cancer by the Division of Gynecologic Oncology and Pelvic Surgery at the Southern California Permanente Medical Group between January 1, 1986, and December 31, 1986, was performed. Fifty-six percent of patients presented with abnormal vaginal bleeding, twenty-eight percent presented with abnormal Papanicolaou (Pap) smears, nine percent presented with pain, four percent presented with vaginal discharge, and four percent presented with other symptoms. Follow-up was 24 to 41 months. Patients presenting with abnormal Pap smears had DFS of 96%. Those presenting with abnormal vaginal bleeding had DFS of 51% and those presenting with pain had DFS of 29%. Presentation strongly influences DFS (chi 2 = 16.8, P less than 0.001). Of women presenting with abnormal Pap smears, 87% were Stage I and 13% were Stage II. Of women presenting with other than abnormal Pap smears, 40% were Stage I, 34% were Stage II, and 26% were Stage III or IV. Presentation with abnormal Pap smear and stage are significantly related (chi 2 = 14.8, P less than 0.001). Of women presenting with abnormal Pap smears, 89% had cancers 0 to 2 cm, 5% had cancers 2.1 to 4 cm, and 5% had cancers greater than 4 cm in diameter. Of women presenting with other than abnormal Pap smears, 21% had cancers 0 to 2 cm, 26% had cancers 2.1 to 4 cm, and 53% had cancers greater than 4 cm in diameter. Presentation with abnormal Pap smear is significantly associated with tumor size (chi 2 = 25.4, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916511 TI - Five-year survival in patients given intra-arterial chemotherapy prior to radiotherapy for advanced squamous carcinoma of the cervix and vagina. AB - Five-year survival studies in patients with advanced gynecologic pelvic malignancy treated with intra-arterial chemotherapy followed by radiotherapy have not been reported in the literature. Forty-six evaluable patients entered into a study between 1981 and 1985 at the University of Texas-M.D. Anderson Cancer Center were reviewed for follow-up. Two patients were FIGO (International Federation of Gynecology and Obstetrics) Stage IIB cervical cancer, thirty-one patients were Stage III cervical cancer, seven patients were Stage IVA cervical cancer, and six patients were unstaged, cut-through cervical cancer, or primary vaginal carcinoma with bulky tumor volume. Seventeen patients had evidence of obstructive uropathy by intravenous pyelogram. Pretreatment lymphangiogram was carried out in 32 patients, 14 of whom were positive for pelvic lymph node involvement. Forty-four patients had received no prior therapy before initiating intra-arterial chemotherapy. Thirty-five (76%) of the patients responded to locally infused pelvic intra-arterial chemotherapeutic agents consisting of mitomycin-C, bleomycin, and cisplatin. Vincristine was given peripherally by intravenous access. There were 24 (52%) partial responders, 11 (24%) complete responders, and 11 (24%) nonresponders. Two (4%) patients progressed during treatment, while twenty-six (57%) patients relapsed after receiving chemotherapy followed by radiotherapy. Three additional patients died from treatment-related causes, one secondary to renal failure, one to massive pulmonary embolus, and one from a combination of pulmonary toxicity secondary to bleomycin and sepsis. Three of fifteen patients in complete remission died from unrelated causes with no evidence of disease. The 5-year survival rate for the study group was 30%, with a median survival duration of 18 months. PMID- 1916512 TI - Selection for percutaneous nephrostomy in gynecologic cancer patients. AB - For patients with gynecologic cancers who present with ureteral obstruction, it is often difficult to determine whether intervention with nephrostomy tube is appropriate. This study was designed to determine if evaluation prior to percutaneous nephrostomy could accurately predict patients who would benefit from intervention. Twenty-two gynecologic cancer patients with bilateral ureteral obstruction were evaluated. Criteria contraindicating intervention included disease progression while on therapy, potentially life-threatening medical problems, Zubrod performance status greater than 2, no available efficacious therapy, noncompliance, and poor pain control. A single criterion was sufficient to contradindicate percutaneous nephrostomy placement. Including replacement nephrostomies, a total of 46 percutaneous nephrostomies and four stents were placed in 19 patients. Three patients had no intervention. Only 9 patients did not have any contradictions to placement of percutaneous nephrostomy, based on predictive criteria. Patients without contraindications to percutaneous nephrostomy survived longer (median days, 242 versus 37; P less than 0.05), had improved quality of life (median days at home, 164 versus 2; P less than 0.05), and had a better chance of receiving therapy after percutaneous nephrostomy (9 versus 2 patients; P less than 0.05). Assessment prior to percutaneous nephrostomy maybe helpful in guiding the physician in recommending intervention. PMID- 1916513 TI - Conservative management of cervical intraepithelial neoplasia during pregnancy. AB - Conservative treatment of a pregnant woman with moderate dysplasia that progressed to microinvasive carcinoma within 6 months is presented along with a review of the relevant literature to date. Pregnancy does not necessarily create special difficulties for the detection and diagnosis of cervical lesions as long as the patient is followed carefully. In this case, close observation using cytology and colposcopy along with colposcopically directed excisional biopsy postponed the need for more aggressive intervention, while minimizing possible disruption of the pregnancy and danger to the mother and infant. A simple hysterectomy performed 6 weeks postpartum proved successful and the cancer has not recurred. PMID- 1916514 TI - Peutz-Jeghers syndrome with ovarian sex cord tumor with annular tubules and cervical adenoma malignum. AB - A patient with Peutz-Jeghers syndrome, a sex cord tumor with annular tubules, and an initially unrecognized adenoma malignum of the cervix is described. The patient presented with a mucinous adenocarcinoma in the vaginal apex. Review of the hysterectomy slides demonstrated an adenoma malignum of the cervix. In addition to a microscopic sex cord tumor with annular tubules of the right ovary, the left ovary contained mucinous cystadenomas. Adenoma malignum remains a difficult diagnosis and is frequently made only after hysterectomy for a presumed benign indication; pathology frequently demonstrates a deeply invasive, unusually well-differentiated adenocarcinoma of the cervix. Patients with Peutz-Jeghers syndrome need careful clinical and cytologic follow-up to exclude such lesions. PMID- 1916515 TI - Aggressive angiomyxoma of the female pelvis and perineum: review of the literature. AB - Aggressive angiomyxoma is an uncommon neoplasm which predominantly involves the pelvis and perineum of young White females. Misdiagnosis is common. Treatment typically involves surgery, and in spite of apparently complete resection, recurrences are common. Local spread into the adjacent fascia and musculature is frequently reported, and rarely, extension into intestine and bladder. The first reported case of pubic bone involvement, including its histology, radiologic features, and operative management, is discussed. Including this patient, 26 women with this tumor have been reported in the literature and are reviewed, along with 2 previously reported cases from the University of New Mexico Tumor Registry. PMID- 1916516 TI - Stage IB glassy cell carcinoma of the cervix diagnosed during pregnancy and recurring in a transposed ovary. AB - A case report of glassy cell carcinoma of the cervix occurring during pregnancy is presented. Clinical staging was FIGO IB and treatment consisted of a radical hysterectomy, bilateral ovarian transposition, and postoperative pelvic radiation therapy. The patient had a relapse in one of the transposed ovaries. A review of ovarian conservation in Stage IB carcinoma of the cervix is discussed. PMID- 1916517 TI - Changing concepts in the management of vulvar cancer. AB - Vulvar carcinoma varies widely in its clinical presentations and prognosis. The reviewed literature outlines the achievements of conventional surgery, radiation, or chemoradiation therapy in its management. Currently therapeutic concepts are evolving. New treatment strategies replacing the uniform use of radical vulvectomy and bilateral groin dissection are proposed. These strategies are tailored to the clinical and pathological disease extent and location and integrate the possible therapeutic advantages of both surgery and chemoradiation. The testing and use of the proposed multimodality therapy protocols require the expertise of gynecologic, radiation, and medical oncologists. This approach should lead to improved anatomic and functional preservation in early disease and improved locoregional in advanced disease. PMID- 1916518 TI - Necrotizing fasciitis: a complication of squamous cell carcinoma of the vulva. AB - Necrotizing fasciitis is an often fatal, often initially unrecognized condition. Although it was first described over 60 years ago, occurrence in the vulva was only first recognized in 1972. The condition is most often associated with diabetes, prior injury, surgery, or irradiation. Aggressive surgical excision is required, early in the course of the disease, to salvage the patient. An association with vulvar carcinoma in a nondiabetic patient has not been previously reported. We report such a case, with a poor outcome, because surgical intervention was not possible until late in the course of the disease. PMID- 1916519 TI - [Therapeutic possibilities for urge incontinence]. PMID- 1916520 TI - [Imaging procedures in the evaluation of bladder changes in female urinary incontinence]. PMID- 1916521 TI - [Acceptance and subjective well-being with a norgestimate combination pill]. AB - 683 women were assessed in the present study. All study participants were subjected to an overall clinical examination before and after a 4-month regimen of a low-dose norgestimate-containing combination oral contraceptive (Cileste); in addition, their subjective well-being was investigated by an appropriate questionnaire. 63.3% of the study participants rated drug tolerance as 'very good' and 23.0% rated it as 'good' at evaluation in the 4th cycle. Between the first and second evaluation, we observed a significant improvement of the depressive mood and of skin and hair problems. Women with skin and hair problems often suffer from 'severe dysmenorrhea'. This difference was statistically significant only at the first evaluation (i.e. before the combined norgestimate regimen) and was not observed in the 4th cycle (i.e. during the Cileste regimen), while the incidence of menstrual disturbances was generally found to decrease. PMID- 1916522 TI - [Vulvar cancer. Bern university gynecologic clinic patients treated 1978 to 1987]. AB - Between 1978 and 1987, 44 women with primary invasive carcinoma of the vulva were treated. The mean age of the patients was 69 years (24-91). The predominant histologic type was squamous cell carcinoma. Thirteen radical vulvectomies were performed. Various other vulvar operative procedures were performed on 27 cases and were followed up with or without radiation therapy. The 5-year survival rate was 80% in stage T1 patients, 58% in T2 and 40% in T3. Patients with negative lymph nodes had a survival rate of 79% after 5 years and those with positive nodes a survival rate of 40%. A modified radical vulvectomy was performed: to the Pary-Jones incision we use an additional groin incision. The advantage is better wound healing as compared to Way's technique. PMID- 1916523 TI - [Does fetal reaction to vibro-acoustic stimulation depend on its activity state?]. AB - The value of vibro-acoustic stimulation of the fetus in predicting fetal well being remains controversial. This prospective randomised study comprised of 25 women with pregnancies ranging between 37 and 41 weeks. The fetal response in each case was investigated before and after a real and a sham stimulation. Each real stimulation led to immediate fetal movements (p less than 0.0001). The fetal reaction was independent of the preexisting behavioral state; vibro-acoustic stimulation can induce a change in the behavioral state. Fetal bradycardia following vibro-acoustic stimulation was not observed. PMID- 1916524 TI - [Gynecologic urology]. AB - Urinary incontinence, urge symptoms and repeated urinary tract infections are among the most frequent ailments seen in women. Usually, they are easily diagnosed and treated effectively using conservative means. If this treatment fails, a urodynamic investigation should be performed. This includes urethrocystometry and a lateral urethrocystography. The diagnosis made through urodynamic exploration leads to a specific treatment, which usually means, in the case of stress urinary incontinence, a surgical procedure. Subsequently, based on our observations and experiences through urodynamic testing and postoperative follow-ups, we present a concept for the treatment of stress urinary incontinence. Furthermore, the benefits and risks of various vaginal and abdominal surgical approaches, as well as some specific modifications, have been evaluated. PMID- 1916525 TI - [Proceedings of the regional divisions of the Italian Society of Hematology. Abstracts]. PMID- 1916526 TI - Parasitic protozoa of cyprinid fishes: protozoa of the roach Rutilus rutilus (Linnaeus, 1758) in Czechoslovakia. AB - In the years 1985-1988, a total of 254 specimens of the roach, Rutilus rutilus, captured in 23 localities of South Bohemia, were examined for the presence of protozoan parasites. Only 17 specimens (6.7%) were free of infection, whereas the others were infected at least with one parasite species, mixed infections were observed most frequently. The following species were found rarely: Myxidium rhodei Leger, 1905 in the liver and muscles. Pleistophora mirandellae Vaney et Conte, 1901 in ovaries, Trichodina nemachili Lom, 1960 on the skin, Trichodina prowazeki Grupcheva et Lom, 1980 on the skin (the first finding in Czechoslovakia). The data concerning localization of individual parasites and their prevalence are presented and five protozoan species described in detail. PMID- 1916527 TI - Variability of the hard parts of opisthaptor of Gyrodactylus leucisci Zitnan, 1964 (Monogenea: Gyrodactylidae). PMID- 1916528 TI - A new Huffmanela species, H. schouteni sp. n. (Nematoda: Trichosomoididae) from flying fishes in Curacao. AB - A new nematode species, Huffmanela schouteni sp. n., has been established on the basis of its egg morphology and biological characters (adult nematodes are unknown). The dark-shelled eggs of this histozoic parasite occur in masses in the abdominal cavity, serose covers of internal organs and in the liver of the flying fishes Hirundichthys affinis Gunther (type host) and Cypselurus cyanopterus Cuvier et Valenciennes in Curacao. The eggs of H. schouteni sp. n. differ from those in other congeneric species mainly in the absence of small spines on the surface of the transparent envelope enclosing the egg proper, measurements (size of eggs 0.069-0.075 x 0.027-0.030 mm) and their localization in the host. A key to Huffmanela species based on egg morphology has been provided. PMID- 1916529 TI - Ultrastructure of the male reproductive system of the trematode Brachylaimus aequans. AB - The transmission electron microscopic studies of the trematode Brachylaimus aequans revealed that the seminal vesicle and ejaculatory duct are lined with syncytial epithelium with numerous lamellate processes. The cirrus and genital pore are covered with a spineless tegument, which is almost identical with the body tegument. The testes contain tailed spermatozoa developing during spermiogenesis from biflagellate spermatids whose flagella (9 + 1) fuse with the median cytoplasmic process. The lumina of seminal vesicle, ejaculatory duct and cirrus are filled with spermatozoa. PMID- 1916530 TI - Studies on the development of the cestode Proteocephalus neglectus La Rue, 1911 (Cestoda: Proteocephalidae) under experimental conditions. AB - A part of the life cycle of Proteocephalus neglectus La Rue, 1911, a parasite of trout, starting from release of eggs from mature parasites into water, to the early phase of development in the definitive host, was studied under experimental conditions. Special regard has been paid to development in the intermediate host, copepod Cyclops strenuus. Some oncospheres in eggs kept in water at 5 and 10 degrees C remained infective for 20-25 days. The percentage of infected copepods depended on the length of their contact with parasite eggs. Cestode larvae (cercoscoleces) were formed in the intermediate host on days 8-10 p.i. at the temperatures of 21-22 degrees C, on days 18-21 at 15 degrees C, on days 24-28 at 10 degrees C, and on days 59-65 at 6 degrees C. Most larvae, including infective cercoscoleces, were localized in the cephalothorax of the intermediate host, particularly in its first segment. This localization did not change during their development. The infectivity of cercoscoleces was verified by experimental infection of Salmo gairdneri fry. The development of the cestode in this definitive host was observed for 17 days after infection at 10 degrees C. The finding of P. neglectus cereoscoleces in fish of the families Cottidae and Cyprinidae on day 2 after experimental infection indicates that these larvae can survive for a short time in atypical fish hosts. PMID- 1916531 TI - Intestinal parasites: a study of human appendices. AB - Histological sections of 414 appendices were examined parasitologically. Enterobius vermicularis was found in 8.7%, eggs of Ascaris lumbricoides in 0.5%, trophozites of Dientamoeba fragilis in 4.8%, Endolimax nana in 2.2%, Entamoeba coli in 1% and cysts of Giardia intestinalis in 1.9% of cases. Appendicopathies associated with Enterobius were most frequent in the age group from 6 to 10 years (24.3%) and from 21 to 25 years (12.2%). Patients older than 15 years were practically women only. Dientamoeba was most frequent in the age group from 11 to 15 years (11.3%). In women D. fragilis was three times more frequent than in men. The coincidence of D. fragilis and E. vermicularis infections was 50%. No interactions were seen between the protozoans in the contents of the appendix and its mucous membrane. Statistical evaluation indicates possible etiologic role of E. vermicularis in the occurrence of acute appendicities. D. fragilis appears to be the most common intestinal protozoan parasite in Bohemia. PMID- 1916532 TI - Redescription of, and comments on, Caligus lacustris Steenstrup et Lutken, 1861 (Copepoda, Caligidae), a parasite of freshwater fishes. AB - Caligus lacustris is the only freshwater species of a marine genus containing some 200 species. Although it is widespread and abundant in extensive freshwater habitats of the Old World, it has never been adequately described and accurately illustrated. This paper provides detailed description and illustrations of C. lacustris, based on new material from the territory of the USSR. PMID- 1916533 TI - Studies on ticks of veterinary importance in Nigeria: intrinsic factors influencing oviposition and egg-hatch of Amblyomma variegatum under natural conditions. AB - During the peak of rains of 1983, 1984 and 1985 in the forest zone of Nigeria, female Amblyomma variegatum engorged to various weights were subjected to different experiments for the purpose of observing the intrinsic factors which influence oviposition and egg-hatch under natural conditions. Two types of oviposition patterns were observed. New terms were introduced to quantify the relationships between the daily weight loss and daily number of eggs oviposited by a tick. These terms are "actual mass", "convertible blood mass", "oviposition efficiency" and "mass conversion rate". A major advantage of adopting the "oviposition efficiency" and "mass conversion rate" is that they relate directly to the measure of the metabolic activity utilized by the tick for the process of oviposition. The entity "convertable blood mass" also enables recognition of individual capability in the utilization of blood mass for oviposition. Investigation on the relationship of weight of eggs with sequence of oviposition showed that eggs were heavier when few eggs were laid than when numerous eggs were oviposited. The heaviest eggs were laid towards the end of oviposition. Two types of relationship were found to exit between the sequence of oviposition and the eclosion period of eggs. Adult A. variegatum engorged to more than 2.49 x were affected by immersion in water for longer than 7 days. Such ticks died without ovipositing and the water in which they were submerged became dark-red. Eggs immersed in water for periods ranging from 1-7 days hatched in about the same number of days as control eggs and their viability in terms of percent-hatch was not affected. PMID- 1916535 TI - Effect of ivermectin on the development of serum antibody activity in rabbits infested with Psoroptes cuniculi (Acari: Psoroptidae). AB - Effect of ivermectin injected subcutaneously in a single dose on the serum specific antibody activity against. Psoroptes cuniculi antigens was studied on four heavily and three weakly P. cuniculi infested rabbits. It has been shown that ivermectin enhanced the production of the specific antibody, especially in weakly infested rabbits. The serum specific antibody activity in both heavily and weakly infested rabbits reached the peak levels on fifth after injection of ivermectin. PMID- 1916534 TI - Occurrence of Aedes aegypti (L.) and Culex quinquefasciatus Say (Diptera, Culicidae) in houses of different constructions in Phnom Penh, Kampuchea. AB - The relation between the number of mosquito specimens of the most abundant species Aedes aegypti (L.) and Culex quinquefasciatus Say and the construction of houses which they inhabited was studied. The effect of the building materials and of the height at which the floor was situated above the ground were assessed in five and four localities, respectively. It was found that in the localities having the character of a town the mosquitoes were most abundant in houses constructed from corrugated plate and in those the floor of which was situated 2 3.5 m above the ground. In the locality of a village character, the mosquitoes were most numerous in brick houses with the floors at the ground level. PMID- 1916536 TI - A new species of the genus Gyrodactylus Nordmann, 1832 (Monogenea) from Gobio gobio (L.). AB - Gyrodactylus dykovae sp. n. (Monogenea: Gyrodactylidae) is described from the fins of the freshwater fish, Gobio gobio (L.) (Cyprinidae), from the Rokytna River near Moravsky Krumlov, Czechoslovakia. This species is most related to G. gobii Shulman, 1953 from which it differs by possessing more robust anchors with considerably larger shaft and by the morphology of the hook proper of marginal hooks. PMID- 1916537 TI - Notes on Gyrodactylus gussevi Ling Mo-en, 1962 (Monogenea: Gyrodactylidae). AB - The authors describe a species which is strikingly similar to the species Gyrodactylus gussevi Ling Mo-en, 1962 on the basis of morphometrical evaluation of 6 gyrodactylid specimens found on the fins of Parasilurus asotus (L.) which was captured in the River Amur near Khabarovsk. Due to inaccurate and incomplete original description of G. gussevi, the authors have to determine this species only provisionally as G. gussevi. As a result of evident appurtenance to G. latus -complex, P. asotus seems to be the "wrong" host. PMID- 1916538 TI - Coypus (Myocastor coypus) as a new host of Cryptosporidium parvum (Apicomplexa: Cryptosporidiidae). PMID- 1916539 TI - Domestic geese (Anser anser L.) as a new host of Cochlosoma anatis Kotlan, 1923. PMID- 1916540 TI - Viviparus contectus as a new intermediate host of Linstowiella viviparae (Linstow, 1877) (Trematoda: Cyathocotylidae). PMID- 1916541 TI - [Effect of (+)-S-145 calcium salt dihydrate, an orally active antagonist of the thromboxane A2/prostaglandin endoperoxide receptor, on platelet aggregation]. AB - The effect of (+)-S-145, (1R, 2S, 3S, 4S)-(5Z)-7-(3-phenylsulfonylaminobicyclo [2.2.1] hept-2-yl) heptenoic acid on human and guinea pig platelet aggregation was examined. (+)-S-145 sodium salt inhibited human platelet aggregation induced by arachidonic acid (AA), 9,11-methanoepoxy-PGH2 (U 46619), collagen, ADP or epinephrine with the IC50 being 0.047-0.146 microM in an in vitro system. When (+)-S-145 calcium salt dihydrate was administered orally to guinea pigs, it inhibited AA-, U-46619- or collagen-induced platelet aggregation dose-dependently with the minimum effective dose being 0.03 mg/kg, and the effective duration being maximally 3 hr. The inhibiting potency and effective duration of (+)-S-145 calcium salt dihydrate after multiple administrations, once a day (0.5 mg/kg) for 7 days, were almost the same as those after a single administration. Although (+) S-145 sodium salt showed a partial agonist effect (shape change) on platelets in vitro, the effect diminished after pretreatment of the platelets with a lower dose of this compound. These data suggest that (+)-S-145 calcium salt dihydrate is an orally effective potent platelet aggregation inhibitor. PMID- 1916542 TI - [Pharmacokinetics and the time course of pharmacodynamics of recombinant human erythropoietin (SNB-5001)]. AB - Pharmacokinetics and the time course of pharmacodynamics of recombinant erythropoietin (SNB-5001) were investigated. The plasma concentration of SNB-5001 reached Cmax at 6-7 hr after the subcutaneous injection and gradually decreased. Most of the SNB-5001 in plasma disappeared at 48 hr. Serum erythropoietin activity changed similarly to plasma SNB-5001 concentration. It was indicated that SNB-5001 moves into the plasma and organs having intact bio-activity after its injection. The decrease in serum iron and increase in unsaturated iron binding capacity (UIBC) began at 8 hr after the injection. Both the trough point of serum iron decrease and the peak point of UIBC increase were 24 hr after the injection. Each value recovered to the initial level at 72 hr. Total iron binding capacity did not change. Increase in reticulocytes began at 24 hr and reached the peak at 72-96 hr after the injection of SNB-5001. Reticulocytes count recovered to the initial level at 120 hr. The pharmacodynamics time course after the subcutaneous injection of SNB-5001 was the same as that after the intravenous injection. It was indicated that SNB-5001 reached an effective plasma level at the earlier absorption phase after the subcutaneous injection. PMID- 1916543 TI - [Effects of recombinant human erythropoietin (SNB-5001) on renal anemic rats induced by drugs]. AB - In order to investigate the clinical usage of SNB-5001 (recombinant human erythropoietin), two types of anemic models induced by drugs were prepared. One group of rats was intravenously injected with 8 mg/kg of cisplatin. These rats temporarily showed leucopenia and thrombocytopenia. Since 2 weeks after the cisplatin injection, rats chronically showed renal failure and moderate anemia. Another group was subcutaneously injected with 15 mg/kg of puromycin, 4 times a week, for 3 weeks. These rats showed hypercholesteremia and hypoalbuminemia, and they showed chronic renal failure and severe progressive anemia. Anemic rats received SNB-5001 (50 or 500 U/kg) once a day for 7 days. In the anemic rats induced by cisplatin, more than 50 U/kg of SNB-5001 dose-dependently increased reticulocytes, red blood cells (RBC), hemoglobin (HGB) and hematocrits (HCT). SNB 5001 apparently improved the anemia induced by cisplatin. On the other hand, in anemic rats induced by puromycin, 50 U/kg of SNB-5001 increased reticulocytes, but did not increase RBC, HGB and HCT. SNB-5001 at the dose of 500 U/kg stopped the progress of anemia in puromycin treated rats. It was suggested that SNB-5001 is useful for the improvement of renal anemia induced by drugs, but the effects are affected by the uremic condition and the stage of renal anemia. PMID- 1916544 TI - [The contractile response of isolated lingual arteries from rabbits treated with bacterial lipopolysaccharide via the stimulation of B1-receptors for kinins]. AB - The effect of intravenous injection of 10 micrograms of a lipopolysaccharide (endotoxin) extracted from E. coli to rabbits on the responses of isolated lingual arteries to des-Arg9-bradykinin (a specific kinins B1-receptor agonist) was studied. Endotoxin injection led to the appearance of the endothelium independent contractile effect of des-Arg9-bradykinin in the arteries; endotoxin elicited this response when administered at 1, 5 or 20 hr before the experiment, in a time-interval dependent manner. The contractile response to des-Arg9 bradykinin of the arteries isolated from animals receiving endotoxin 20 hr before the experiment was attenuated by des-Arg9-[Leu8]-bradykinin (a specific inhibitor of kinins B1-receptor) or pretreatment of the animals with an inhibitor of protein synthesis (cycloheximide and actinomycin D). When compared with the effect of des-Arg9-bradykinin, bradykinin (a potent kinin B2-receptor, but weak B1-receptor stimulant) caused slight contraction of the arteries; however, this effect was not endotoxin-dependent and was not modified by des-Arg9-[Leu8] bradykinin. Effect of in vitro preincubation with endotoxin of the arteries isolated from animals receiving saline 20 hr before the experiment was further studied. The preincubation (for 1 and 5 hr) with endotoxin of the arteries in the presence or absence of plasma had no effect on the sensitivity of the arteries to des-Arg9-bradykinin; the sensitivity was also unaffected in the presence or absence of endotoxin, thus suggesting that there is no interaction between endotoxin and some plasma-related factors with the appearance of the contraction in response to the kinin B1-receptor agonist in the arteries in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916545 TI - [Effect of AS-2646, a novel antiulcer agent on gastric mucosal defensive factors in rats]. AB - The effects of AS-2646 on the acute gastric mucosal lesions induced by various noxious agents and the gastric mucosal defensive factors were studied in rats, and the following results were obtained: 1) AS-2646 (5-100 mg/kg, p.o.) dose dependently inhibited the formation of the mucosal lesions induced by ethanol, ethanol-HCl, taurocholate-HCl and serotonin, and its anti-lesion spectrum was the widest among the compounds (cimetidine, pirenzepine, sulpiride and prostaglandin E1) examined here. 2) AS-2646 (5-10 mg/kg, p.o.) not only improved the changes of gastric mucosal hemodynamics induced by the blood removal and/or the reserpine treatment, but also inhibited the mucosal lesions induced by them. 3) AS-2646 (2 20 mg/kg, p.o.) antagonized the decrease in the surface gastric mucus and mucosal hexosamine contents induced by stress and/or aspirin. 4) AS-2646 (2-20 mg/kg, p.o.) caused no significant effect on the gastric mucosal prostaglandin E2 levels. 5) AS-2646 inhibited Campylobacter pylori in vitro. These results indicate that AS-2646 may be useful as a novel antiulcer drug with the defensive factor-potentiating and anti-Campylobacter pylori effects. PMID- 1916546 TI - [Effects of ovariectomy on naloxone-modulated hypertension in spontaneously hypertensive rats (SHR)]. AB - Ovariectomy was performed at 4 weeks of age (W), and the rats were used when they were 33 and 75 W old. Systolic blood pressure (BP) was measured by the tail-cuff method. Naloxone (10 mg/kg) was given i.p. Catecholamines (CA) were determined with HPLC. Norepinephrine (NE) was not significantly altered in intact rats by naloxone; however, a significant increase in NE appeared in the plasma, hippocampus, thalamus plus mid-brain and hypothalamus in castrated rats following naloxone. With naloxone treatment, dopamine (DA) was significantly increased in the plasma and hypothalamus, but decreased in the cerebral cortex in intact rats; and with castrated rats, there was a tendency to see an increase in plasma DA and significantly increased levels of DA in the thalamus plus mid-brain and hypothalamus. This suggests that in female brain, lack of estrogen in the castrated rats leads to an increase in intrinsic opiate, and this in turn inhibits CA release. On the other hand, when naloxone was administered to castrated rats, intrinsic opiate was blocked, and, consequently, inhibition of CA release was lost and induction of CA release was enhanced. PMID- 1916547 TI - [Evaluation of HCl-induced gastric mucosal lesions using a computer image processing system]. AB - Oral administration of HCl (0.2 N, 0.4 N, 0.6 N, 0.8 N) solution produced congestive or hemorrhagic gastric mucosal lesions in rats. Lesion areas were differentiated into two areas (i.e., brown area and black area) macroscopically. Then, fine observations were performed on two areas using a computer image processing system (CIPS) and histological techniques. Cell necrosis from the mucosal surface to the middle mucosal layer were observed in the brown area, and gastric mucosal necrosis that reached to a deeper layer were observed in the black area. These results indicate that histological degree of lesion may be reflected in the macroscopic changes. Concerning the concentration of HCl, over 0.4 N HCl solution induced mucosal lesions, but HCl solution (0.4 N HCl) only produced a brown area. Maximum changes in the mucosal surface were observed at 30 min to 1 hr by 0.6 N HCl and at 15 to 30 min by 0.8 N HCl. Therefore, the best condition for evaluating the preventive effects of anti-ulcer agents is 30 min after treatment by 0.6 N HCl solution and 15-30 min after treatment by 0.8 N HCl solution. These results suggest that this technique may provide both quantitative and qualitative information on histological changes. PMID- 1916548 TI - Characteristics of nodules through the high-resolution frequency analyzer. PMID- 1916549 TI - Voice fatigue after theater performance in actors. PMID- 1916550 TI - Variability of phonetograms. AB - Various sources of phonetogram variation were investigated, i.e. graphs showing voice sound pressure level (SPL) for a speaker's loudest and softest phonation at different fundamental frequencies. The short-term SPL variation within a vocalization was analyzed for 10 female and 10 male normal speakers and for 10 female patients with nonorganic dysphonia, i.e. patients with insufficient voices and no indication of pathology according to microlaryngostroboscopy. This variability was about 5 dB in soft phonation and less in loud phonation. The agreement between 2 investigators independently determining SPL for identical vocalizations by means of a sound-level meter was also studied and found to be quite good. The long-term variation was analyzed in 1 male and 1 female normal subject in 15 phonetogram recordings made on different days; the standard deviation averaged across fundamental frequency and subjects was found to be approximately 3 dB. The implications of these findings for a clinical use of phonetograms are discussed. PMID- 1916551 TI - Embryological considerations of distinctive feature theory. AB - The role of the physiology is emphasized here, perhaps to the eventual denial of the importance of the acoustic cues involved at these stages. The acoustic cues are the result of the physiology and are a further development of the features of speech. The selection of the sounds of babbling is a function of the physiological readiness and is an internal function [Locke, 1983]. Sounds are produced that are not used in final adult speech [Locke, 1983]. It is the acoustic cues of the environment that perhaps cause the 'babbling drift' toward adult speech of the environment [Brown, 1958]. In line with the above-mentioned ideas regarding branchial arch development, most of the components of the outer and middle ear are derivatives of the first branchial arch, which though limited musculature is involved, especially for sound perception, might downplay the role of acoustics at these earliest stages even further. If it can be said that cortical organization and representation development follow a similar sequence as is evidenced from the branchial arches and their derivatives, the importance of acoustic stimuli, at this point, would be even further questioned for these early stages. The assumption should be made that a muscle or muscle group does not function prior to this established branchial arch pair sequence. The major distinction here has been utilization of the structures in a 'conscious', deliberate, voluntary manner with a specific goal in mind. The babbling and even feeding that children undergo provides evidence that these structures function perhaps long before any sequence of branchial arch pair developmental sequence can be applied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916552 TI - [Psychosocial aspects of sexuality in the elderly woman]. AB - In the doctor's office, counseling in matters of sexuality in the aged is rare, and scientific data are sparse. Speculative literature is of little use. Normative ideas from earlier decades need to be checked for their present-day validity. Sexuality as a learning process and form of communication is relatively constant, so that few generalizations are possible. A widely accepted theory is that of non-use, which means in analogy to the mental faculties in aging a steady decline of sexual functions. The possibilities for sexual activity in age are impaired not only by illness and the side effects of drugs; rather, the difference in life expectancy in men and women is also becoming ever more relevant. Thus, today, 1/7 of the 70-75 men are widowed compared with 50% of the women of the same age--three times as many. By the year 2000, 15% of the population will be aged 85 or older. The expected ratio of women to men is 2:1. Elderly women suffer from depression that lasts for weeks about three times as often as men. Possible consequences in the sexual area should be considered. PMID- 1916553 TI - [Sexual counseling of elderly patients]. PMID- 1916554 TI - [Hormonal changes in aging from the viewpoint of the gynecologist]. AB - The major relevant age-related changes that take place in women are caused by estrogen deficiency of rapid onset. This deficiency results in such changes as vaginal and vulval atrophy, atrophic urethrocystitis, breast flabbiness, thinning of the skin and its appendages, and also the severe metabolic changes like osteoporosis and cardiovascular disorders. All of these changes, in concert or alone, are capable of impairing a woman's sex life. Numerous genital complaints can be eliminated by local treatment with estriol cream, estriol vaginal suppositories, or systemic estriol. For the successful treatment of pronounced menopausal symptoms and the prevention of osteoporosis and cardiovascular disorders, estrogens at medium, so-called replacement, doses, given in combination with progestagen, are applied sequentially. PMID- 1916556 TI - [Peripheral facial paralysis. 1: Diagnosis--examinations]. PMID- 1916555 TI - [Lipoprotein metabolism in menopause. Effect of hormonal substitution therapy]. AB - Oral administration of conjugated estrogens, estradiol valerate and micronized estradiol--but not the percutaneous application--in the postmenopause modifies the plasmic lipoprotein profile by lowering, dose-dependently, LDL and elevating HDL (HDL2). In parallel, the cardiovascular mortality is decreased by 50-66%, with smokers also benefiting to the same extent. On account of the increased risk for endometrial carcinoma associated with postmenopausal estrogen monotherapy, combination with a lowest-dose gestagen is imperative. However, the very numerous synthetic gestagens can antagonize the favorable effects of the estrogen on lipoprotein metabolism. This applies in particular to the gestagens of the 19 nortestosterone type, such as norethisterone acetate and, in particular, levonorgestrel, but less so the 17-hydroxyprogesterone derivatives medroxyprogesterone acetate and medrogestone with their very low androgenic effect. PMID- 1916557 TI - [Mineral metabolism and aluminum burden with hydrotalcit. A placebo-controlled randomized double-blind study]. AB - In a randomized, double-blind study, the influence of hydrotalcit (aluminium magnesium hydroxide carbonate hydrate) on the mineral metabolism was investigated. No significant and clinically relevant changes in calcium, phosphate, magnesium or aluminium concentrations in the serum were observed. Nor were these substances eliminated in greater amounts in the urine. Merely the elimination of magnesium was higher in the group receiving the test substance than in the placebo group; after discontinuation of the medication, no difference in the elimination rates was found. Thus, provided that renal function is intact, the use of hydrotalcit does not lead to any disturbance in the mineral balance, or, in particular, to any additional aluminium burden. PMID- 1916558 TI - [Pediatric immunodeficiency ambulatory care for interdisciplinary management]. PMID- 1916559 TI - [Classification of uv light as dangerous and safe?]. PMID- 1916560 TI - [Sinusitis in the child from the ENT specialty point of view]. AB - In the child, acute sinusitis generally accompanies infections of the upper airways, so that, as a rule, treatment of the infection also deals with the sinusitis at the same time. Against this background, clinical diagnosis is adequate, and further diagnostic measures--in particular x-ray examinations, are superfluous. Only if the child feels really ill, or if inflammation spreads to the orbits is a diagnostic x-ray required. Bacterial superinfection, in particular with orbital involvement, necessitates massive antibiotic treatment and, where appropriate, the exclusion of an abscess and/or intracranial complications. In clinically healthy children, radiopacities can often be seen on the x-ray of the paranasal sinuses, in which case, we are dealing with an occult sinusitis. In general, this clears up spontaneously, and only rarely needs treating. Polypous sinusitis in childhood is rare and requires surgical therapy. PMID- 1916561 TI - [Peripheral facial paralysis. Part 2: Therapy of peripheral facial paralysis- facial hyperkinesia]. PMID- 1916562 TI - [Combination therapy in chronic heart failure. Hemodynamic effects with a calcium antagonist-diuretic combination]. AB - In twelve patients with chronic cardiac insufficiency (NYHA II-III), the effect of a fixed combination of drugs (160 mg verapamil/50 mg triamterene/25 mg hydrochlorothiazide) on cardiac hemodynamics was studied over a period of four weeks. During the course of treatment, the arterial blood pressure decreased from 145 +/- 16/93 +/- 9 mmHg to 133 +/- 18/86 +/- 14 mmHg, and the heart rate from 79 +/- 13 to 75 +/- 12 beats/min. Exercise blood pressure (900 watts) decreased from 180 +/- 22/104 +/- 14 mmHg to 158 +/- 25/96 +/- 17 mmHg and the heart rate from 104 +/- 14 to 100 +/- 16 beats per min. After treatment, a decrease in pulmonary arterial pressure and resting pulmonary capillary wedge pressure (PPA:-2.3 mmHg, PPC:-1.4 mmHg) and in exercise pressure (PPA:-8.5 mmHg, PPC:-6.6 mmHg) was established. Clinically relevant changes in cardiac output and cardiac index were not observed. The subjective symptoms (NYHA stage) were improved in eight patients. Combination treatment would appear suitable for patients with mild-to moderate cardiac insufficiency. PMID- 1916564 TI - ["Sydney system". A new world-wide gastritis classification]. PMID- 1916563 TI - [Pharmacologic advantages of individual cholesterol synthesis inhibitors? Prof. Dr. Dr. med. W. Schunack, Free University Berlin, elaborates on differential therapeutic considerations]. PMID- 1916565 TI - [Serum cholesterol and coronary sclerosis]. AB - Among both the general population and physicians, there is considerable uncertainty as to the significance of elevated cholesterol levels. Many laboratories consider all values above 200 mg/dl to be abnormal or undesirable. Taking the case of a 66-year-old lady doctor as an example, arguments against such an undifferentiated view are advanced. It is concluded that cigarette smoking continues to be the major risk factor for coronary heart disease, and every effort should be made to reduce it. Elevated cholesterol levels alone usually have no clinical significance; they should be assessed only in conjunction with other blood parameters, but also with age and sex. PMID- 1916566 TI - [20 years kidney transplantation. Experience of a practice]. AB - Between September, 1969, and May, 1990, 1,086 kidney transplantations were performed in Freiburg. In the majority of cases, the transplantations were allografts and had been made possible by close cooperation with the Eurotransplant Foundation. The results of this long-term study show that the transplant function rates at one year in the period under observation were comparable. Only the introduction of the immunosuppressive agent cyclosporine A brought about any improvement. On the basis of the results achieved at our center, the HLA system had an influence on transplantation function rate only in the case of the DR system. However, this does not mean that, for organ matching, the HLA system should no longer be complied with, since multicentric studies have substantiated its importance. High-risk groups, such as diabetics and elderly patients who undergo a transplantation achieve the same good results as the low risk groups, provided that each case is carefully considered on its individual merits. PMID- 1916567 TI - [Detection of side effects. 1: Spontaneous detection of drug risks- responsibility of the physician]. PMID- 1916568 TI - [Constant beta blockade around the clock. Drug study in general practice conditions]. PMID- 1916569 TI - [Secondary prevention of stroke in relation to its cause. Prof. K. M. Einhaupl gives references for more controlled prevention. Interview by T. U. Keil]. PMID- 1916570 TI - [Meteorism]. AB - Gastrointestinal bloating is a common complaint met within the general practitioner's office. The most important cause of this symptom is an increase in the volume of gas in the gastrointestinal tract. Differential diagnoses include aerophagia, ingestion of gas-producing foods, gastric hypersecretion, bacterial overgrowth in the small intestine, disordered gastrointestinal transit, malabsorption or maldigestion of carbohydrates. In addition, nonulcer dyspepsia and the irritable bowel syndrome must be excluded. The diagnosis is based on a history of eructation, heart burn, flatulence and diarrhea, dietary habits, physical examination, laboratory analysis and apparative diagnostic measures. Therapy depends on the underlying cause of the disease. PMID- 1916571 TI - [Neuronal colon dysplasia in adulthood. Diagnosis, clinical aspects and therapy]. AB - In patients with primary chronic constipation (n = 18) and diverticulosis of the sigmoid (n = 17) biopsies were examined enzyme-histochemically and the diagnosis of neuronal colonic dysplasia of the rectosigmoid was established. In eleven controls however a normal innervation was observed (p less than 0.001). Patients with neuronal colonic dysplasia usually failed to respond to conservative methods of treatment. Indication for surgery depended upon the duration and severity of the symptoms. The actual treatment--partial lateral submucous sphincterotomy, resection of the sigmoid colon or subtotal colectomy--was determined by the extent of the morphologically and functionally altered intestinal segment. PMID- 1916572 TI - [Detection of side effects. 2: Responsibilities of the pharmaceutical industry, drug commissions, the Federal Health Office and international organizations]. PMID- 1916573 TI - [Pain therapy with non-prescription analgesics]. PMID- 1916574 TI - [Controversy over natural healing procedures. Interview by Elizabeth Moosmann]. PMID- 1916575 TI - [HIV infection. The French have no fear of AIDS]. PMID- 1916576 TI - [Neurodermatitis: good results from therapy. Reader's opinion on pathogenesis]. PMID- 1916577 TI - [Mycoplasma fermentans changes HIV pathology. Cytotoxicity--syncytia formation]. PMID- 1916579 TI - [Risks of unconventional viruses for man. Results of modern technology]. PMID- 1916578 TI - [Glucocorticoid therapy in childhood]. AB - In children, too, treatment with glucocorticoids may occasionally be necessary. On the one hand, replacement treatment in children with the adrenogenital syndrome, on the other pharmacotherapy in a number of diseases may be required. The latter include the genuine nephrotic syndrome, autoimmunological diseases, hypsarrhythmia, and, in the field of neonatology and neonatological intensive care, the treatment of the respiratory distress syndrome and bronchopulmonary dysplasia. Side effects of pharmacotherapy include suppression of the adrenal cortical function and growth disorders, together with truncal obesity, formation of striae of distension or osteoporosis. PMID- 1916581 TI - [Alcohol-induced ketoacidosis. 1: symptoms, diagnosis, differential diagnosis]. PMID- 1916580 TI - [The effect of topical heparin on histamine-induced wheals. A double-blind study]. AB - Since it is difficult to demonstrate the effectiveness of heparin-containing ointments in the treatment of thrombophlebitis under clinical conditions, a double-blind experimental trial was performed in 18 volunteers. To produce a reproducible inflammation, ten drops of a histamine solution containing 10 mg histamine/100 ml, were applied to an area measuring 4 x 7 cm2 on both forearms of each test subject. Under each drop, the skin was pricked five times. Ten minutes after induction of inflammation, one forearm of each subject was treated in a double-blind randomized manner with an ointment containing heparin (50,000 IU heparin/100 g), the other arm being treated with the heparin-free ointment base. As a criterion of the effectiveness of the ointment, the course of the temperature of the forearms was measured using thermography. Ten minutes after application of the histamine solution, the temperature increased by a mean of about 3 degrees centigrade. After 30 minutes' treatment with heparin-containing ointment, the temperature then decreased by 1.77 degrees C, while that of the forearms treated with heparin-free ointment base decreased by only 1.14 degrees C. The difference was statistically significant (p less than 0.001). Sixty minutes after treatment the differences were still significant at p = 0.012. This study thus demonstrates the effectiveness of heparin-containing ointment in the treatment of histamine-induced inflammation. PMID- 1916582 TI - [Therapy of hypertensive coronary patients. Open long-term study with a combination of atenolol and nifedipine]. AB - In the present study, 20 patients with both hypertension and stabile angina pectoris were treated twice daily for 6 months with 50 mg atenolol and 20 mg retard-formulation nifedipine. The effect of this treatment on blood pressure and heart rate was investigated at rest and under standardized ergometric conditions, and by means of a 24 h Holter ECG. The frequency of angina pectoris episodes in 6 week periods was reduced by 34% over 6 months. The initial decrease in systolic and diastolic blood pressure (by 25%) was maintained over the long term at rest and under exercise. Patient exercise tolerance with reduced oxygen utilization, as represented by the product of pressure x rate, showed a lasting improvement. After 6 months, monotopic ventricular premature beats in particular were reduced significantly (46%) as compared with the initial situation. PMID- 1916583 TI - [The Stasi persecution syndrome]. AB - For many years western psychiatrists only out of their clinical experience have known about a syndrome for which the name Stasi-persecution-syndrome will be used here. Stasi was the all powerful secret police of what was the East German Democratic Republic. The syndrome concerns an hitherto unknown number of the aprox. 50,000 survivors. It is a sequel of a form of persecution now more generally named torture. The characteristics of the persecution include arrestion, interrogations, degradation, humiliation, maltreatment, assault, mass detention in tiny rooms, hunger, cold, discrimination, defamation, disgrace, outlaw, social degradation, absence of rights, uncertainty of future, life threatening, and stigmatizing. The sequels resemble in many aspects of what is known by the psychiatry of the persecuted, but own a special flavor. Among the sequels are persisting and paranoid anxieties, re-arousable by specific situations. There are also realistic anxiety and persecution dreams, mood disturbances, lack of confidence, attempted suicide and complaints about lack of understanding by others, which the victims suffer from. Questions of indemnification for psychiatric sequelae have entered into a new stage after the East-German parliament had passed a rehabilitation bill and because of corresponding declarations in the unification treaty. Psychiatrists should fight for treatment costs and appropriate compensation for physical and psychiatric sequels of Stasi persecution to be set into reality as soon as possible. There is urgent need for a not yet existing scientific literature and publications of clinical experiences. PMID- 1916585 TI - [Psychotherapy in schizophrenic psychoses--historical development, effectiveness and currently accepted methods]. AB - Psychotherapy has a long tradition in the treatment of schizophrenic psychosis. Individual therapies--based on psychoanalysis in continental Europe and in the first half of this century due to emigrants in England and the United States- were predominant. The development of family therapy then led to modified forms and in particular group therapy for relatives of schizophrenic patients. There is a variety of treatments available today: assistance in coping with the disease, cognitive therapies and social skill training, psychotherapy based on depth psychology, family therapy and work with the relatives of patients. Some encouraging studies on efficacy are already available. Drug treatment continues to be the dominant form of therapy, but modified psychotherapeutic programs for patients and their relatives have become an important supplement to neuroleptic therapy and relapse prevention, particularly since the "Vulnerability-Stress Hypotheses" became widely accepted. PMID- 1916584 TI - [Overcoming disease and biography of lumbar disk surgery patients--a typology based on 30 case studies]. AB - A random sample of 30 patients hospitalized for lumbar disc surgery was studied on four specific occasions: before surgery in a biographic interview; during post operative treatment by behavioural observations; at discharge from hospital and 15 months on average after surgery in further interviews about their ability to cope with the illness and about their social adaptation. Data analysis was carried out according to the method of structural hermeneutics (Oevermann et al. 1979). By contrastive comparison of the cases, a typology of coping behaviour in patients during the out-patient, in-patient, and post-hospitalization phase was developed. 15 patients showed a consistent type of coping behaviour which we have termed "autonomistic". This finds expression at the behavioural level in a patient-doctor struggle who determines treatment. It is motivated by an ambivalence conflict between fear of and desire for dependence and care. Variants of autonomistic coping behaviour and their dependence on biographic influences are presented using 2 case histories. Against this background the problem of adaptivity is discussed. PMID- 1916586 TI - [Femoral nerve lesion in heparin therapy]. AB - Two case reports on femoral nerve lesion due to hematoma in the iliopsoas muscle or as the case may be in the iliacus muscles on both sides are presented with review of the literature. Synopsis of the reported cases--certainly a minority of anticoagulant therapy complications nevertheless increasingly mentioned in the literature--suggests that there might be a higher risk of bleeding for women within the first week of so-called high-dose heparin therapy. Coagulation studies do not contribute essentially in preventing retroperitoneal haematoma since they are within therapeutic limits in many cases. So clinical observation is crucial in the diagnosis of this complication of heparin therapy, which might occur more frequently under concomitant administration of acetacylic acid. Early surgical decompression of the femoral nerve seems to provide better results seen on follow up than conservative treatment, especially in patients with rapid onset of severe limb weakness. PMID- 1916587 TI - [Toxicological assessment of 2,5,2',5'-tetrachlorobiphenyl and its major metabolite, 3-hydroxy-2,5,2',5'-tetrachlorobiphenyl in rats]. AB - We observed previously that polychlorinated biphenyl (PCB) could be classified to two groups, 3-methylcholanthrene (MC)-type and phenobarbital (PB)-type, in term of inducibility of the hepatic enzymes. MC-type PCBs such as 3,4,3',4' tetrachlorobiphenyl (TCB), 3,4,5,3',4'-pentachlorobiphenyl (PenCB) and 3,4,5,3',4',5'-hexachlorobiphenyl (HexCB) exhibited high acute toxicity in parallel with their induction ability of microsomal benzo[a]pyrene 3-hydroxylase and cytosolic DT-diaphorase. On the contrary, PB-type PCBs such as 2,5,2',5'-TCB and 2,4,5,2',4',5'-HexCB which induce microsomal benzphetamine N-demethylase and NADPH-cytochrome P-450 reductase activities showed virtually no or very low toxicity. In the present study, we examined effects of 2,5,2',5'-TCB and its major metabolite 3-hydroxy-2,5,2',5'-TCB on body weight gain, organ weights and activities of hepatic enzymes in rats and assessed acute toxicity of these compounds. As the results, in both 2,5,2',5'-TCB and 3-hydroxy-2,5,2',5'-TCB groups, the body weights were increased during the experiment, but the rate of growth was significantly suppressed after 3 days. Significant hypertrophy of the liver and decrease of total liver lipid content were observed in 2,5,2',5'-TCB group, but the atrophy of spleen and thymus was not affected in both groups. On the other hand, in 2,5,2',5'-TCB group, benzo[a]pyrene 3-hydroxylase and benzphetamine N-demethylase activities were increased to 2. 4-fold and 1.5-fold, respectively, but were not increased in 3-hydroxy-2,5,2',5'-TCB group. After injection of 2,5,2',5'-TCB, 45% of the dose was excreted as 3-hydroxy-2,5,2',5' TCB in feces for 5 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916588 TI - [Acute toxicity, inductive effects of liver enzymes and distribution in the liver of 1,2,3,7,8-pentachlorodibenzo-p-dioxin in rats]. AB - Acute toxicity, inductive effects of liver enzymes and liver persistency of 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PenCDD) were compared with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) using male Wistar rats. 1,2,3,7,8 PenCDD treatment at a dose of 0.1 mumol/kg resulted in significant depression of growth of rats from a day to 28 days after treatment. However, the effect was relatively less than that of 2,3,7,8-TCDD. On 5 days, similarly to 2,3,7,8-TCDD treated group, liver hypertrophy and thymic atrophy were observed in 1,2,3,7,8 PenCDD-treated groups. In addition, 1,2,3,7,8-PenCDD showed potent 3 methylcholanthrene-type inducing ability. For example, the activities of benzo(a)pyrene 3-hydroxylase and DT-diaphorase were 25-fold and 10-fold of control, respectively. On 30 days, about 50% of the inductive effects on 5 days were maintained in both 1,2,3,7,8-PenCDD- and 2,3,7,8-TCDD-treated groups. Amount of 1,2,3,7,8-PenCDD distributed to the liver on 5 days was about 80-90% of dose and was about 1.5 times greater than that of 2,3,7,8-TCDD. About 50% of dose of 1,2,3,7,8-PenCDD remained even on 30 days after treatment. From these results, it is suggested that 1,2,3,7,8-PenCDD possessing the potent acute toxicity comparable to 2,3,7,8-TCDD and higher persistency in the liver might be more important than 2,3,7,8-TCDD in terms of the chronic toxicity. PMID- 1916589 TI - Effects of 3-methylsulphonyl-4,5,3',4'-tetrachlorobiphenyl and 7,8-benzoflavone on aryl hydrocarbon hydroxylase activity in Ah responsive and Ah nonresponsive strains of mice. AB - In general, C57BL/6NQdj (C57) and DBA/2JCrj (DBA) strains of mice are considered to be the aryl hydrocarbon (Ah) responsive and Ah nonresponsive strains of mice, respectively, which are determined by whether the hepatic aryl hydrocarbon hydroxylase (AHH) activity is enhanced (Ah responsive) or not (Ah nonresponsive) after the treatment of 3-methylcholanthrene (MC). In this study, first, we examined that the Ah responsiveness was systemically regulated in the lungs and kidneys as well as in the liver and observed its systemic control in these three organs in the two strains of mice. Then, we prepared the hepatic microsomes of the two strains of mice after the treatment of MC (42 mg/kg, once), 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD, 20 micrograms/kg, 6 times) and 2,3,4,7,8 pentachlorodibenzofuran (PenCDF 60 micrograms/kg, 6 times) in order to investigate the effects of 3-methylsulphonyl-4,5,3',4'-tetrachlorobiphenyl (3-MSF TCB, 1.5-45 micrograms/ml) and 7,8-benzoflavone (ANF, 1.4-42 micrograms/ml) on the respective hepatic microsomal AHH activities and the following results were obtained. 1. As compared with the control enzyme activity, TCDD-induced AHH activity was the highest, PenCDF-induced one the second and MC-induced the lowest in both strains of mice. The inductions of the enzyme activity by these chemicals were much more remarkable in the Ah responsive C57 strain than those in the Ah nonresponsive DBA strain. 2. 3-MSF-TCB and ANF enhanced or reduced the enzyme activity depending on both their concentrations and kinds of microsomes, namely, those prepared from untreated control mice and mice treated with MC, TCDD or PenCDF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916590 TI - The synergistic effect of chlorinated chemicals (trichlorosalicylanilid, 4-chloro m-cresol, trichlorophenoxyacetic acid, trichloroethanol, trichloromethiazide, trichlorofon and trichloroacetaldehyde) and low concentrations of griseofulvin on porphyrin metabolism. AB - The synergistic effect of chlorinated chemicals and 0.1% griseofulvin (GF) on porphyrin metabolism was investigated. Drinking water containing 0.03% trichlorosalicylanilid, 0.1% 4-chloro-m-cresol, 0.1% trichlorophenoxyacetic acid, 0.3% trichloroethanol, 0.1% trichloromethiazide, 0.3% trichlorofon and 0.1% trichloroacetaldehyde was given separately to dd-y strain mice. Each group was divided into two subgroups, one treated with feed containing 0.1% GF and the other treated with normal feed. The treatments were continued for 45 to 165 days, after which porphyrins in the erythrocytes, feces and liver were analyzed by a chromatographic method. In the 0.03% trichlorosalicylanilid and 0.1% GF group, 0.1% 4-chloro-m-cresol and 0.1% GF group, 0.1% trichlorophenoxyacetic acid and 0.1% GF group and 0.3% trichloroethanol and 0.1% GF group, a slight elevation of fecal coproporphyrin and protoporphyrin was seen. There was no elevation of hepatic and erythrocytic porphyrins. This result shows that the chemicals used in this study did not have a potential for porphyria, but that they are capable of inducing slight porphyrin abnormalities in a synergistic reaction with 0.1% GF. PMID- 1916591 TI - [The effect of organochlorine compounds on the induction of sister chromatid exchanges in cultured human lymphocytes]. AB - In this study, first, we investigated the effect of 7,8-benzoflavone (ANF), mitomycin C (MMC), a well-known genotoxic compound, and ANF plus MMC on the induction of sister chromatid exchanges (SCEs) in human whole-blood cultures. Second, we examined the effect of mixture of organochlorine compounds, which very resembled their contamination of healthy people in its composition, on the induction of SCEs in the same blood culture system in order to clarify their genotoxicity as a whole. The following results were obtained. 1. ANF and MMC significantly enhanced the number of SCEs/cell at the concentrations of 4 x 10( 5) M and 10(-8)M, respectively. When both of the compounds were simultaneously added in the blood cultures, their effects on the induction of SCEs seemed to be additive. 2. Without ANF in the blood culture system, namely, an usual system of the SCEs experiment, we could not find a dose-response relationship between the concentration of the mixture of organochlorine compounds and the induction of SCEs/cell. With ANF, however, we observed a fairly good dose-response relationship between them. 3. In the whole-blood culture system with ANF, we found significantly great number of SCEs/cell at the level of twenty times higher concentration of the organochlorine compounds than the ordinary level. According to the results described above and of our other studies, 50% effective concentration (EC50, about 2 SCEs/cell higher than control SCEs/cell) of the mixture was considered to be about 5 times greater level over the general one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916592 TI - [Influences of polychlorinated dibenzofuran on pUC18 plasmid DNA]. AB - We investigated an effect of polychlorinated dibenzofuran (PCDF) on pUC18 plasmid DNA. The mixtures of pUC18 and PCDF were introduced into the competent cells derived from E. coli. The competent cells were cultured on Luria-Bertani agar plate containing ampicillin. The number of colonies was not decreased in compared with it of E. coli inserted non-treated pUC18. The pUC18 re-extracted from the E. coli with PCDF-treated pUC18 were digested with 15 kinds of restriction enzymes and agarose gell electrophoresed. As the results no changes were found in compared with non-treated pUC18. Those findings suggested that the PCDF did not react with pUC18. PMID- 1916593 TI - In vitro analysis of polychlorinated biphenyls (PCBs) and 2,3,4,7,8 pentachlorodibenzofuran (PCDF) cellular toxicity in PLC/PRF/5 cell proliferation- the effect of ursodeoxycholic acid, inchin-gorei-san and shou-saiko-to on cell toxicity. AB - We investigated the cell toxicity of polychlorinated biphenyls (PCBs) and 2,3,4,7,8-pentachlorodibenzofuran (PCDF) as an indicator of the quantity of m RNA, which synthesizes the HBV core antigen region, and secreting protein, which is an HBV surface antigen in PLC/PRF/5 cells. The determination of m-RNA was conducted according to the methods of reverse transcriptase and polymerase chain reaction. Furthermore, the reductive action of ursodeoxycholic acid, shou-saiko to and inchin-gorei-san on the PCBs and PCDF toxicity was investigated. The cell number of 1 x 10(5)/ml and concentrations of 200 micrograms/ml for PCBs and 500 microM for PCDF were used in these experiments. The titer of HBsAg was gradually increased from 1 in 1 x 10(3)/ml of cell numbers to 100 in 1 x 10(6)/ml of cell numbers. The curve became a plateau in 1 x 10(6)/ml of cell numbers. The cell number of 1 x 10(5)/ml was used in the experiments. The titer of HBsAg decreased following in the increase of concentration of PCBs. The HBsAg, even in the PCBs concentration of 1000 micrograms/ml showed a titer of 22.5%. However, the highest concentration of PCDF in this study, that is, 500 microM of PCDF, did not show any decrease of HBsAg activity. The concentrations of 200 micrograms/ml for PCBs and 500 microM for PCDF were used in the investigation of drug effects. A high titer HBsAg was observed in high concentrations of shou-saiko-to in comparison with a control group. Ursodeoxycholic acid and inchin-gorei-san exhibited a similar tendency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916594 TI - [A study of epidermal alterations induced by PCDF on experimental carcinogenesis]. AB - An effect of 2,3,4,7,8-pentachlorodibenzofuran (PCDF) as a promoter on a course of experimental skin carcinogenesis in mice by chemicals 20-methylcholanthrene (MC) has been proved by our previous studies. Details of ultrastructural epidermal alterations induced by MC and PCDF were observed and an attempt to differentiate benign tumor from malignant one in which a combined application of MC and PCDF on mice skin resulted was done electron microscopically. Four significant findings as follows were detected. First of all even the epidermal cells without tumor had some atypicality. Secondly both of benign tumor and normal-appeared skin without tumor had giant and round-shaped keratohyalin granules (KHGs) which show a tendency of less keratinization. Thirdly cytoplasmic projections of epidermal cells increased in number and sparse tonofilaments scattered in the cytoplasm of benign tumor. This is also an appearance of mucous metaplasia of keratinocytes as well as the form of KHGs mentioned above. Finally benign tumor had thick horny cells including numerous lipid droplets, and that is a sign of acceleration of epidermal turn over. Since epidermal cells have little chance to be exposed to carcinogens when they quickly keratinize, they rarely form a cancer. When epidermal cells have such tendency as less keratinization or more keratinization, they are supposed to be less sensitive to any stimuli of carcinogens, and consequently they incline to be benign tumor instead of malignant one. PMID- 1916595 TI - [Carcinogenicity of 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7,8 hexachlorodibenzofuran when given by gavage to rats]. AB - Previous studies showed that 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) could produce tumors in the liver and subcutaneous tissues of rats by subcutaneous administration. The present study has examined the carcinogenicity of the same compounds in rats by oral administration. Wistar strain male rats were sacrificed at two years after oral administration (0.2 mg/rat) of 2,3,4,7,8-PenCDF or 1,2,3,4,7,8-HCDF. Among rats given 2,3,4,7,8-PenCDF, a cholangiohepatoma and a osteosarcoma were revealed in a rat each. Moreover, a few hepatic nodules were found in two rats in each experimental group. These results suggest that these compounds of polychlorinated dibenzofurans have a tumorigenic potency by oral administration. PMID- 1916596 TI - [Carcinogenic effects of polychlorinated biphenyls (PCBs) and their derivatives, including carcinogenicity to the lung]. AB - PCBs are compounds whose physical/chemical properties led to their wide spread commercial use. The persistence and stability of PCBs have resulted in a world wide distribution. PCDFs, ones of PCB derivatives, are primary causal agents of mass food poisoning, called Yusho in Japan and Yu-Cheng in Taiwan. Several epidemiologic studies on the carcinogenicity of PCBs in both occupational exposure and accidental intoxication suggest that PCBs might be a potent carcinogen in liver and lung. Many investigators reported that PCBs induced hepatocellular carcinoma in rat and mice. Although either mutagenic or genotoxic effects of PCBs are not definite, their tumor promoting effects have been repeatedly demonstrated in the liver. The effects of PCBs as tumor promoter in the lung have also been reported. PCB congeners that efficaciously promote carcinogenesis increase cytochrome P-450-dependent monooxygenases, which are abundant both in bronchiolar Clara cells and in hepatocytes. PCB congeners which are inducers of P-450 may be active as tumor promoter by inhibiting intercellular communication and/or by stimulating cell proliferation. Furan derivatives like PCDFs have high affinity to bronchiolar Clara cells and hepatocytes. PCDFs induce necrosis and epoxide formation to their target cells, which might result in carcinogenesis of liver and lung. PMID- 1916597 TI - [Immunohistological and histopathological study of the effect of PCB on the periodontal tissue]. AB - We performed immunohistochemical and histopathological investigation on the inflamed gingiva from the patient with Yusho and on the periodontal tissue from PCB poisoned rats respectively. The results obtained were as follows. 1) In the gingiva from the Yusho patients, the proportions of plasma cells, B cells, T cells in the inflammatory cells and CD4/CD8 ratio were 47.9%, 18.3%, 10.7%, and 2.84, respectively. 2) In the periodontal tissue from rats with experimental periodontitis, we found no definitive difference between the PCB poisoned rats and the clinically healthy rats. PMID- 1916598 TI - [Elimination of PCDF and PCB congeners in the blood of patients with PCB poisoning in Taiwan]. AB - The blood of 3 Yu-cheng patients sampled from 1980 to 1989 were analyzed for congeners of polychlorinated dibenzofurans (PCDF) and polychlorinated biphenyls (PCB) by high resolution gas chromatography-mass spectrometry and gas chromatography-electron capture detection. The high concentrations of 2,3,4,7,8 penta-, 1,2,3,4,7,8-hexa- and 1,2,3,4,6,7,8-hepta-CDFs (15.4, 37.7 and 4.8 ppb in lipid basis, respectively) were eliminated from the blood at half-lives of 2.14, 2.56 and 2.32 years, respectively. The high concentrations of 8 PCB congeners in the blood were also decreased with time at half-lives of 1.16-4.56 years. The half-lives of retainable PCB congeners were about 2 times longer than those of the PCDF congeners. PMID- 1916599 TI - [PCB methyl sulphone: comparison of tissue levels in Baltic grey seals and a Yusho patient]. AB - Methyl sulphone metabolites of PCB and DDE were isolated from different tissues of a Baltic grey seal (Halichoerus grypus). Main components in the seal blubber were identified as 3-MeSO2-2,2',4',5,5'-pentaCB, 4-MeSO2-2,2',4',5,5'-pentaCB, 3 MeSO2-p,p'-DDE, 4-MeSO2-2,2',3',4',5-pentaCB and 4-MeSO2-2,2',3,4',5',6-hexaCB. Liver and lung in the seal contained different MeSO2-PCB pattern compared to all other tissues. These levels in the both tissues were estimated to be 28 and 15 ppm (lipid basis) which corresponded to the same level as the PCB. Concentrations of MeSO2-PCB in any tissues of a Yusho patient were low compared to those in the seal. PMID- 1916600 TI - [Coplanar PCBs, PCDFs and PCDDs in the subcutaneous adipose tissue of Yusho patients and normal controls]. AB - 3,4,3',4'-tetrachlorobiphenyl (T4CB), 3,4,5,3',4'-pentachlorobiphenyl (P5CB) and 3,4,5,3',4',5'-hexachlorobiphenyl (H6CB) [Co-PCBs] in the subcutaneous adipose tissue of seven Yusho patients and eight normal controls were determined to assess the contribution in the risk caused by the Yusho causual agents (PCBs, PCDFs, PCDDs and Co-PCBs) by using high resolution gas chromatography/high resolution mass spectrometry in selected ion monitoring mode. 3,4,3',4'-T4CB, 3,4,5,3',4'-P5CB and 3,4,5,3',4',5'-H6CB were detected in the subcutaneous adipose tissue of the Yusho patients at the levels, of 6 to 29 ppt, of 32 to 130 ppt and of 160 to 1,140 ppt, respectively. The TCDD-Eq (Equivalents) value calculated by TCDD-TEfs (Toxic Equivalent factors) was from 8 to 30 ppt. On the other hand, 3,4,3',4'-T4CB, 3,4,5,3',4'-P5CB and 3,4,5,3',4',5'-H6CB were detected in the subcutaneous adipose tissue of normal controls at the levels, of 3 to 9 ppt, of 41 to 280 ppt and of 47 to 200 ppt, respectively. The TCDD-Eq value calculated by TCDD-TEfs was from 9 to 57 ppt. In the Yusho patients, the average TCDD-Eq value calculated by TCDD-TEfs of the residual Co-PCBs, PCDFs and PCDDs was 17, 491 and 24 ppt, respectively. Therefore, we concluded that the typical symptoms for the Yusho patients are caused mostly by PCDFs. PMID- 1916601 TI - [Studies on the application of residual PCBs, PCQs and PCDFs concentrations to Yusho diagnosis]. AB - Results of Yusho annual inspection were reviewed from the view point of correlation of PCBs, PCQs and PCDFs concentration in blood or subcutaneous adipose tissue and clinical findings. To make discussion quantitative, fifteen terms of clinical findings on Yusho disease were quantified on the severity by evaluating (+) as 2 points, (+-) as 1 point and (-) as 0 point. First, the temporal variations of the severity of clinical findings on 5 Yusho patients were figured. Additionally, the temporal variations of blood triglyceride and PCBs concentration, and GOT were also surveyed. The adopted terms of clinical findings were general malaise, cough, sputum, headache, abdominal pain, peripheral neuropathy, soreness of joints, deformity of nails, comedo formation, acne-like eruption, secondary infection, scar formation, disorder of Meibomian glands, edema of eye lids and increased discharge from the eyes. During the investigated period from 1972 to 1988 the total score of clinical findings clearly decreased on two patients who had high score, tended to decrease on two other patients, and was not clear on another patient. Secondly, the correlation coefficients were calculated between each of PCDFs, PCBs or PCQs concentration in subcutaneous adipose tissue or blood and the total score at the year in which the adipose tissue and blood were taken. For the female patients the correlation coefficient of PCDFs concentration in subcutaneous adipose tissue and total score of clinical findings was the highest of all (r = 0.9885). However, for the male patients it was not available because the number of the subjects was only two. Thus far it has been reported that the powers of PCBs gas chromatogram pattern and PCQs concentration as criteria for Yusho diagnosis are low as for the subjects who belonged to the border area between Yusho patients and normal persons. This survey suggests that PCDFs concentration in subcutaneous adipose tissue can be a potent criterion that has a high correlation with the clinical findings of Yusho. PMID- 1916602 TI - A comparative study on the concentrations of polychlorinated biphenyls (PCBs) and polychlorinated quaterphenyls (PCQs) in the blood and hair of "Yusho" patients and inhabitants of Nagasaki Prefecture. AB - The relationship between polychlorinated biphenyl (PCB) and polychlorinated quaterphenyl (PCQ) concentrations in the blood and hair was investigated. The materials in this study consisted of 49 blood samples and hair obtained from 27 patients with PCB poisoning (Yusho) and 22 normal controls. The alkaline decomposition method described in the official standard analytical methods for the isolation of PCB and PCQ fractions was used. In the blood of the control group, the mean concentration of PCBs was 2.25 ppb, while the concentration of PCQs was too low to be detected by our analytical method. On the other hand, the mean concentration of PCBs in the Yusho group was about 2.8 times higher than that in the control group. The mean concentration of PCQs in the blood was 0.61 ppb in the Yusho group, but PCQs were not detectable in the control group. In the hair, the mean concentration of PCBs was 25.85 ppb and 9.41 ppb in the Yusho group and control group respectively. The mean concentration of PCQs in the hair of Yusho patients was 0.44 ppb, but PCQs were not detected in the control group. The PCB level in the hair was higher than that in the blood, but the PCQ level in the hair was lower than that in the blood. These results suggest a difference of excretory system among polyhalogenated compounds such as PCBs or PCQs. We consider that PCBs display a greater affinity than PCQs for the pilosebaceous system of the human skin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916603 TI - [Studies on distribution and excretion of squalane in dogs administered for 2 weeks]. AB - In the previous papers, we demonstrated, by using rats, that squalane (2,6,10,15,19, 23-hexamethyltetracosane) could stimulate the fecal excretion of 2,3,4,7,8-pentachlorodibenzofuran, the most important etiologic agent of Yusho, which was accumulated in the body of rat. We also reported that, in rats and dogs, squalane did not show any appreciable toxic signs during 3-month treatment, though a part of squalane was absorbed from gastrointestinal tract of dogs. In the present paper, we have investigated the elimination of absorbed squalane in beagle dogs. During the treatment with squalane orally at a dose of 1200 mg/kg/day for 14 days, the fecal excretion of squalane per day was 65-90% of the daily dose. After the treatment (on the day 14), squalane levels in blood and hair were about 30 ppm and 14640 ppm, respectively. On the day 56 after the first dosing, squalane was not detected in blood. On the day 70, squalane level in hair was reduced to about 1% of that on the day 14. Squalane levels in skin, liver, adipose tissue and small intestine on the day 70 were also reduced compared with that on the day 42. Moreover, small amount of squalane was still excreted into feces from the day 15 to the day 70. These results suggested that absorbed squalane was gradually excreted through feces and skin in dogs. PMID- 1916604 TI - [Therapeutic trial for promotion of fecal excretion of PCDFs and PCBs by the administration of cholestyramine in Yusho patients]. AB - Any effective therapy for elimination of causal agents remaining in Yusho patients was not found until now. To know the profile of fecal excretion of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs), the amounts of PCDFs and PCBs in the stool of six Yusho patients with the typical symptoms were determined. The stool samples of Yusho patients were collected in 1989. PCDFs, i.e., 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8 pentachlorodibenzofuran (PnCDF), 1,2,3,4,7,8- and 1,2,3,6,7,8 hexachlorodibenzofurans (HxCDFs), 1,2,3,4,6,7,8-heptachlorodibenzofuran (HpCDF) and octachlorodibenzofuran (OCDF) were detected in all of the samples. PCDFs found in the stool samples were mostly PnCDF and HxCDFs. Of PCDFs detected, PnCDF and HxCDFs contributed to 42 +/- 4.7% and 43 +/- 5.5% as mean +/- SE, respectively. The fecal excretion of PnCDF and HxCDFs in Yusho patients was 720 +/- 490 pg/day and 790 +/- 620 pg/day as mean +/- SE, respectively. On the other hand, the fecal excretion of PnCDF and HxCDFs in normal controls was 32 +/- 13 pg/day and 47 +/- 5.2 pg/day as mean +/- SE, respectively. The fecal excretion of PnCDF and HxCDFs in Yusho patients was about 23 times and 17 times each higher than that in normal controls. The fecal excretion of PCBs in Yusho patients and normal controls was 400 +/- 430 ng/day and 150 +/- 39 ng/day, respectively, as mean +/- SE. In order to promote the excretion of these toxic chemicals in the stool of Yusho patients, the patients were continuously administered with cholestyramine, an anion exchange resin, at a dose of 4 g, 3 times a day, for 6 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916605 TI - [Treatment of Yusho patients with cholestyramine]. AB - Six typical Yusho patients (3 men, 48-58 years old, and 3 women, 45-55 years old) were treated with cholestyramine, 8-12 g/day, for 24 weeks. Improvement of some symptoms, such as arthralgia and malaise, was observed in 2 men, although this effect was non-specific. None of the patients showed increment of excretion of polychlorinated biphenyl or polychlorodibenzofuran into feces. PMID- 1916606 TI - [Associations between blood PCB level and symptoms of Yusho patients, twenty years after outbreak]. AB - To investigate relationships between blood PCB (polychlorinated biphenyls) level and symptoms of Yusho patients, twenty years after outbreak, a comparative study was designed in accordance with the results of medical examination conducted in 1988. For this examination, standardized forms were introduced in 1986, and a whole system for data-processing has been completed through two-years' efforts. Study subjects were 259 Yusho patients (male: 136, female: 123) for whom PCB concentration in blood was reported, among a total of 285 patients examined (91%). And 31 examination items which correspond or relate to the diagnostic criteria for Yusho (1976) were selected from the examination form for analysis. Mean blood PCB concentration in the subjects was 4.78 ppb ranging 0.6-32.0 ppb. The subjects were stratified for four blood PCB levels, less than or equal to 2.6 ppb; less than or equal to 4.0 ppb; less than or equal to 6.0 ppb; greater than 6.0 ppb, by dichotomized categories (normal/abnormal) for the results of each examination. This two-by-four table was transformed to two-by-two table with a cut-off point where the largest chi 2-value was obtained. Then the odds ratio (OR) adjusted for gender and age was calculated for the examination item which showed a statistically significant decrease or increase in crude odds ratio, to assess the association between blood PCB level and symptoms of Yusho patients. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916607 TI - [Ocular manifestations of Yusho 22 years after the onset]. AB - Ocular manifestations were studied in 91 Yusho patients who took the contaminated rice oil 22 years ago. Tear film dysfunction was examined using the rose bengal test. Eighty-seven percent of the patients complained eye discharge, although edema of the eyelid and pigmentation of the conjunctiva were rarely seen. Cystic swelling of the tarsal glands was seen in 16 patients (18%) and white cheese-like contents in the tarsal glands were detected in 7 patients (8%). Twenty-five patients showed positive staining with the rose bengal test, although the intensity of the staining was slight. From this study it appears that there may not be tear film dysfunction in Yusho patients. PMID- 1916609 TI - [Vasopressin and cardiovascular control]. PMID- 1916608 TI - [Dermatological findings in the annual examination of the patients with Yusho in 1989-1990]. AB - We reported the skin symptoms of the patients with Yusho in the 1989 and 1990 annual examinations. We also studied the alteration of the skin symptoms in 33 patients followed up for 14 years (1977-1990). Most of these patients showed obvious improvement in their skin symptoms during 12 years (1977-1988). However, a remarkable improvement was not observed in recent 3 years and approximately 40% of the patients still had comedones and/or acneiform eruptions. PMID- 1916610 TI - Do prescribers know the results of key clinical trials? GEP (Groupe d'etude de la Prescription). AB - A survey was run on a sample of 134 French GPs from the Rhone-Alpes region, in an attempt to investigate the way they recollect important clinical trials that should have an impact on their practice. It was found that 1) most of them did not remember these trials (however, the awareness score did vary throughout the trials); 2) the correlation between prescription claims and awareness score was very poor. PMID- 1916611 TI - Determination of free concentration of piroxicam and naproxen in plasma. The influence of experimental conditions in equilibrium dialysis. AB - An equilibrium dialysis method was established in order to investigate possible relationships between free drug concentrations of piroxicam and naproxen and clinical events. Therefore the influence of variations in pH, phosphate concentration and sodium azide concentration of the dialysis buffer on the free concentrations of piroxicam and naproxen was investigated. Piroxicam was found to have a pH-dependent protein binding. Therefore a good control of pH during the dialysis process is necessary. This has been achieved by increasing the buffer capacity of the dialysis buffer, by adding an antibacterial agent to the dialysis buffer and by cleansing the dialysis cells with 70% ethanol before use to prevent bacterial growth. Addition of 0.03% sodium azide as an antibacterial agent and the use of a 0.09 mol/l phosphate buffer gave good pH control. A method to correct for deviations of pH in measurements of free concentrations of piroxicam by a simple mathematical correction has been found. As naproxen was found to have a protein binding independent of pH, a pH-correction is not necessary for this drug. Standardized conditions in determination of protein binding of drugs by equilibrium dialysis are important, as composition of the dialysis buffer and pH of plasma compartment at equilibrium may influence the free concentration measurements. Comparisons of data from experiments using different methods are therefore difficult; the importance of pH-control is stressed. With the methods used in the present investigation, equilibrium dialysis in connection with HPLC, the coefficients of variation for piroxicam and naproxen free concentrations are 5.5% and 7.4%, respectively. PMID- 1916612 TI - Salicylic acid disposition in children with rheumatoid arthritis. AB - The plasma level profile of SA and SUA after a single oral dose of ASA was studied in 8 children with juvenile rheumatoid arthritis, aged 3.5-15.0 years. Pharmacokinetic parameters were on average similar to those reported in the literature for adult subjects, although a somewhat larger intersubject variability was found. PMID- 1916613 TI - The uterotonic action of the aqueous extract of Bridelia atroviridis in the rat. AB - The effects of the aqueous extract of leaves of Bridelia atroviridis (Bridelia), a small African tree, on the mechanical activity of rat uterus were studied. The aqueous extract of leaves of B atroviridis administered in a concentration dependent manner (5 x 10(-6)-1.2 x 10(-3) g/ml) induced contractions that were antagonized by various calcium entry blockers (nifedipine, diltiazem, manganese chloride). In absence of external calcium ions, repeated applications of a supramaximal concentration of Bridelia (1.2 x 10(-3) g/ml) evoked sustained and repeated contractions the amplitude of which was congruent to 20% of those obtained in the physiological external calcium concentration. Bridelia-induced contractions in calcium-free medium were inhibited by isoprenaline (8 x 10(-7) M), caffeine (15 x 10(-3) M) and trifluoperazine (10(-5) M). Contractile responses induced by Bridelia in both calcium-containing and calcium-free media were antagonized by prior incubation of uterus with phorbol 12, 13-dibutyrate (6 x 10(-7) M), cholera toxin (6 x 10(-8) M) or pertussis toxin (5 x 10(-7) g/ml). These results show that Bridelia has a potent uterotonic action in the rat. The cellular basis of this action appears to be complex, and involves various mechanisms including calcium mobilization from both intra and extracellular compartments and activation of phospholipase C through a G-protein. PMID- 1916614 TI - Effects of administration route on valproate pharmacokinetics in the rabbit. AB - The absorption of sodium valproate was studied in 5 rabbits. Each animal received the drug (70 mg/kg) via 3 routes: intravenous, gastric and duodenal. For the 2 extravascular routes, the absolute bioavailability F, maximal plasma concentrations Cmax, times to peak Tmax and absorption coefficients Kabs were the same. Absolute bioavailability was always close to unity. This indicated that valproic acid was absorbed from the intestine as well as from the whole gastrointestinal tract. The other pharmacokinetic parameters such as terminal plasma half-life, total clearance and volume of distribution remained unchanged whatever the route of administration. PMID- 1916615 TI - Nifedipine alters serum theophylline levels in asthmatic patients with hypertension. AB - The effect of nifedipine on serum theophylline levels in 13 female hypertensive patients having asthma on theophylline therapy has been investigated. Administration of a slow release theophylline product in a dose of 200 mg bidaily for 15 days provided a steady-state through serum theophylline concentration (11.2 +/- 2.7 micrograms/ml). After this period, 10 mg bidaily nifedipine was added to therapy and trough serum theophylline levels, pulmonary function tests and blood pressure measurements have been performed following 15 and 45 days of simultaneous use of theophylline and nifedipine. No change has been observed in serum theophylline level after 15 days of simultaneous use, however after 45 days, serum theophylline level was significantly lower (7.3 +/- 1 micrograms/ml). There were no changes in clinical responsiveness of either of these drugs. PMID- 1916616 TI - Lack of evidence of ketoprofen kinetic changes during the oestrous cycle in rats. AB - This study was designed to document possible changes in ketoprofen kinetics in female rats related to the stage of the oestrous cycle. At 3 different stages of the oestrous cycle (proestrus, oestrus or dioestrus), 3 different groups of 5 animals each received a single 10 mg/kg intraperitoneal dose of ketoprofen and blood samples were taken at 0.25, 0.5, 0.75, 1, 2, 4, 8, 12 and 24 h after administration. Ketoprofen pharmacokinetic parameters (Cmax, T1/2 alpha and beta, AUC and MRT) were calculated. Our data did not reveal any significant differences in ketoprofen kinetics related to the oestrous cycle. PMID- 1916617 TI - [Special aspects of physical training during the rehabilitation stage of coronary patients]. AB - Practical aspects: Physical exercise is a basic component of the rehabilitation program for patients recuperating from myocardial infarction or bypass surgery. The aim of exercise is to enhance physical performance by improving coordination, flexibility, strength, speed and endurance. The training concept is matched to the individual capability, which is determined by an exercise test at the beginning of the rehabilitation program. On the basis of this test, an "exercise heart rate" is calculated with the aim of protecting the patient from overstrenuous activity. Depending on their physical fitness, the patients are divided into two groups: those with a capability of less, and those with a capability of more than 1 watt/kg. Most elderly patients are no longer active participants in sports, so that guidance through flexibility and coordination exercise is offered. Usually, patients perform a daily program of 15 minutes of physical activity in their individual groups, and spend 45 minutes walking and relaxing. In addition, they have opportunities for swimming, jogging and cycling. Decreased left-ventricular function: The effects of a four-week training program in myocardial infarction (MI) patients with moderate-to-severe left-ventricular dysfunction were investigated in two distinct studies. In neither study was a deterioration in the ejection fraction at rest or during exercise observed. In the second study, an additional parameter was provided by the Swan-Ganz catheter. Neither pulmonary wedge pressure (PWP) nor cardiac output indicated any deterioration in response to dosed training. However, in this second study, four patients in the training group with a resting ejection fraction (EF) less than 30% developed complications. All these patients had a pathological PWP at rest. Nevertheless, five patients with an EF less than 30% but with a normal PWP at rest completed the training program without complications. The long-term prognosis for training post-MI patients with severe left-ventricular dysfunction would appear to be no worse than for controls. Results of the first study: During the four-week training program, no complications occurred. No major changes in the EF at rest and during training were seen. In the training group the EF at rest increased slightly to 40 +/- 10%. The EF during exercise improved to 39 +/- 10%. Delta EF showed a decrease of 3 +/- 8%. After the four-week training period the decrease was 1 +/- 9%. In the control group, a major increase in the EF at rest to 41 +/- 10% was seen. The EF during exercise, however, showed only a small increase to 43 +/- 15%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1916618 TI - Cardiovascular benefits of physical activity. AB - Animal studies have consistently shown increased heart strength, size, and vascularity in wild animals compared to domestic animals. While exercise has not been shown to decrease atherosclerosis in either animals or humans, it has been theorized that exercise makes the heart more resistant to ischemia through stimulation of collateral vessel formation and enlargement of already existent coronary arteries. In humans, the benefits and dangers of exercise have been researched with morphological, hemodynamic, and epidemiological studies. Many of these are discussed here as well as the national fitness recommendations made by various health organizations. A summary of the cardiovascular benefits of exercise as supported by the literature is then presented. PMID- 1916619 TI - [Modification of risk factors through physical training and low-fat diet]. AB - This intervention program investigated the applicability and the effects of intensive physical exercise and low-fat diet on the progression of coronary atherosclerotic lesions and stress induced myocardial ischemia in patients with stable angina pectoris. Patients participating in this study were recruited following routine coronary angiography for angina pectoris. Inclusion criteria were male sex, stable symptoms, a willingness to participate in the study for at least twelve months, and coronary artery stenoses well documented by angiography. Exclusion criteria were unstable angina pectoris, left main coronary artery stenosis greater than 25% luminal diameter reduction, severely depressed left ventricular ejection fraction (less than 35%), significant valvular heart disease, insulin-dependent diabetes mellitus, primary hypercholesterolemia (type II hyperlipoproteinemia, low-density lipoprotein greater than 210 mg/dl), and conditions precluding regular physical exercise. 18 patients participated in this program for one year; they consumed a low-fat, low-cholesterol diet (less than 20 energy % fat, cholesterol less than 200 mg/day) and exercised for more than 3 h/week. Myocardial oxygen consumption was estimated from maximum rate-pressure product at peak exercise; it was correlated to stress induced myocardial ischemia, as measured by 201Tl-scintigraphy. Results were compared with those of 18 matched patients on "usual care". In the intervention group, physical work capacity (161 +/- 34 W vs. 194 +/- 42 W) and maximum rate pressure product (25.0 +/- 6.3 x 10(3) vs. 27.2 +/- 5.3 x 10(3)) increased significantly (p less than 0.01). Patients willing to devote time and effort to intensive physical exercise and to comply with a low-fat diet may benefit from this form of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916620 TI - Exercise training in patients after heart transplantation. AB - The post-cardiac transplantation patient is frequently debilitated as a result of "end-stage" heart disease and typically demonstrates muscle wasting, with a reduced work capacity, maximum heart rate and peak oxygen uptake. At submaximal effort perceived exertion and ventilation are higher, and the absolute ventilatory threshold lower, than in normals. A number of published studies have now shown that an exercise rehabilitation programme can induce a good training effect, although possibly not complete restoration of physiological function. The prescription of exercise must take into account the denervated heart's peculiar response to effort, and rely more on perceived exertion and metabolic measurements for defining intensity of training rather than target training heart rates. Changes in mood and personality have also been noted in these patients, and while these may improve spontaneously with the passage of time, there is some evidence that a rehabilitation programme can help in this regard. PMID- 1916621 TI - [Can the training of coronary patients be monitored by readily measurable parameters?]. AB - The prognosis of coronary patients in terms of the mortality of coronary heart disease shows a positive relation to the severity of clinical and functional diagnostic parameters. Thus exercise therapy should be monitored by criteria that take ischemia, the myocardial situation and rhythm disorders into account. These criteria should be reliable and should be easy to determine as well as to apply. For pragmatic reasons the non-invasive evaluation of findings and the diagnostic symptom-limited ergometer test are especially significant for dosage and monitoring of exercise therapy. Monitored exercise therapy is here understood to mean individually adjusted exercising by patients, and training thus has to be based on diagnostic findings. First existing complaints have to be analyzed and such findings as size of infarction in the ECG, heart volume in the X-ray, size and function of the left ventricle by echography, etc. checked. Afterwards maximum physical work capacity on a multistage bicycle ergometer test is measured with respect to the following termination criteria: a) subjective reports by the patient during exercise (e.g. onset and severity of angina pectoris, dyspnea and/or fatigue of the leg muscles) and b) objective criteria such as significant ischemic ST-depression, exercise-hypertension, age-related submaximal heart rate and significant rhythm disorders. An inverse correlation is found between measured maximum symptom-limited physical performance and the frequency of cardiac termination criteria; a comparable inverse correlation exists with heart volume: max. O2 pulse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916622 TI - [Quality of life and personal satisfaction following heart transplantation: an indicator of treatment results]. AB - Cardiac transplantation is an established method of treatment to prolong survival in terminally-ill patients with severe heart disease. This study was undertaken to evaluate the quality of life and its best expression as satisfaction in patients who had undergone cardiac transplantation one year previously. From a total of 47 patients (14 with coronary artery disease, 27 with dilated cardiomyopathy and six with valvular heart disease), self-assessment questionnaires were completed to judge postoperative improvement/deterioration (change of status) and satisfaction with the level achieved as designated on the basis of visual analogue scales. Quality of life and satisfaction were assessed in nine categories: physical, emotional, mental, vocational, sexual status, financial situation, leisure activities, partnership and overall quality of life. The data was analyzed with the Wilcoxon and Kruskal-Wallis tests. The patients reported a consistent improvement in quality of life and satisfaction with respect to all categories except financial situation. Accordingly, quality of life after cardiac transplantation can be regarded as substantially improved. While most marked improvement was incurred in physical status and, consequently, overall quality of life, there was also a meaningful salutary effect on psychosocial aspects of life such as emotional well-being and leisure time activities. There were significant differences between change of status postoperatively and satisfaction with the level achieved in the categories of mental and vocational status, financial situation and partnership as well as family relations. Statistical analysis showed that outcome with respect to quality of life and satisfaction was not dependent on the underlying disease or the age of the patient at the time of transplantation. PMID- 1916623 TI - [Subjective sleep disturbances and psychosocial states in long-term abstainers]. AB - To evaluate the relation between subjective sleep disturbances and psychosocial factors in alcoholics, we studied the subjective estimate of sleep, occupation, marital status, and economic status in 210 abstainers, using check lists which were given to each patients (169 answerers, 82. 9% recovery). We also performed psychological tests of Yatabe-Guilford Personality Inventory in 145 subjects, Maudsley Personality Inventory in 115, and Cornell Medical Index in 103. The results were as follows: 1. Sleep disturbances were seen in 100 abstainers (59.2%). 2. The abstainers who had abstained for less than 2 years showed higher incidence of sleep disturbances than those who had abstained for 2 years or more (70.7% and 37.5%, respectively). 3. The abstainers with sleep disturbances were more frequently unemployed, more frequently divorced, and had lower economic status than those without sleep disturbances (69.0% vs. 36.3%, 31.0% vs. 17.4%, and 49.0% vs. 23.2%, respectively). 4. Three psychological tests suggested that abstainers with sleep disturbances had more immature and neurotic personalities. The present study suggests that the occurrence of sleep disturbances in abstainers may be relevant to their psychosocial states. PMID- 1916624 TI - [Effect of blood hemoglobin concentration on anaerobic threshold]. AB - Anaerobic threshold (AT) has been advocated as an objective method of evaluating exercise capacity in patients with chronic congestive heart failure. The factors that determine AT, however, remain still unclear. To assess the influence of oxygen transport capacity on AT, patients with iron deficiency anemia were studied before and after treatment with iron. Twenty-nine female subjects were studied. They were divided into the following 3 groups: 1) iron deficiency anemia (group IDA: Hgb less than 11 g/dl and ferritin less than 10 ng/ml) consisting of 4 athletes and 6 non-athletes, 2) latent iron deficiency (group Lat-ID: Hgb greater than or equal to 11 g/dl and ferritin less than 10 ng/ml) consisting of 4 athletes, and normal (group Nor: Hgb greater than or equal to 11 g/dl and ferritin greater than or equal to 10 ng/ml) consisting of 15 athletes and 6 non athletes. By bicycle ergometer using ramp protocol, peak oxygen uptake (peak VO2) and AT were measured in each group. Following the 1st exercise testing, groups IDA and Lat-ID were treated by oral iron for 1-1.5 months. The 2nd exercise testing was then performed. Furthermore, to investigate whether muscle cell energy metabolism itself is altered by iron deficiency, P magnetic resonance spectroscopy (MRS) was performed in 2 relatively severe anemic patients during forearm exercise while assessing the changes in phosphocreatine and inorganic phosphate. Peak VO2 and AT in non-athletes were significantly lower in IDA group than Nor group (peak VO2 (ml/min/kg): 23.7 +/- 5.1 vs 33.3 +/- 3.8, p less than 0.01, AT (ml/min/kg): 15.9 +/- 3.3 vs 21.3 +/- 1.3, p less than 0.01). After iron administration, Hgb was increased significantly in IDA group (from 9.0 +/- 1.8 to 12.1 +/- 0.8 g/dl, p less than 0.01) accompanied by an improvement in peak VO2 and AT (peak VO2 (ml/min/kg): from 34.2 +/- 12.4 to 40.0 + 13.0, p less than 0.001, AT (ml/min/kg): from 20.9 +/- 6.3 to 25.0 +/- 8.0, p less than 0.001). Lat ID and Nor groups showed no changes. MRS indices of cell energy metabolism of the 2 severely anemic patients did not differ from those of normal controls, and no changes were observed after iron treatment. It is concluded from these results in iron deficiency anemia that oxygen transport is a determinant of anaerobic threshold. PMID- 1916625 TI - [Histological investigation on hydroxyapatite ceramics as materials of artificial bone grafts in the cervical spine]. AB - The purpose of this study is to understand the utility of the hydroxyapatite (HA) ceramics as artificial bone graft substances in the cervical spine. METHOD: Dense and porous HA were implanted into the vertebral body and intervertebral space of the adult dog cervical spine and the implanted cervical bones were removed 4, 8 and 24 weeks after implantation and examined by contact microradiography (CMR), and histological observations of the non-decalcified material stained with Van Gieson's and decalcified material stained with hematoxylin and eosin. RESULTS AND CONCLUSION: 1. Sufficient formation of new bone with the bone marrow was recognized on the surface and in the pores of the porous HA being implanted to the cervical vertebra. 2. Dense HA was inadequate for the implantation into cervical areas because of its physical nature, such as glass-like smooth surface and the extreme hardness. 3. HA was not fit for usage in the intervertebral space of the cervical spine because of its total ineffectiveness in the functions such as the supporting heavy weight of the head and the mobility and its histologically poor activity of the new bone formation in the intervertebral space. PMID- 1916626 TI - [Mechanisms of ventricular tachycardia induced by electrophysiological methods in humans]. AB - To clarify the mechanisms of ventricular tachycardia (VT) in humans, sixty patients (average age, 43.9 +/- 15.6 years) with life-threatening VT were examined electrophysiologically. Multielectrode catheters were inserted to the heart and programmed electrical stimulation was performed to induce VT. VT was inducible in thirty (50%) of 60 patients. In twenty-nine (93.6%) of these 30 patients VT was induced by ventricular extrastimuli, suggesting that the most important mechanism for the induction of VT is reentry. Background of VT was idiopathic (IDIO) in 36 patients. The remaining 24 patients had underlying heart disease (HD), and only two of them had old myocardial infarction; this was considerably different from that in USA and Europe in which more than 70% of patients with VT have ischemic heart disease. Induction rate VT (IRVT) in IDIO and HD were both 50%. IRVT in 46 sustained VT was 63% and it was significantly higher than that in 14 non-sustained VT (7.1%). The QRS morphology of VT was complete right bundle branch block (RBBB) pattern in 33 patients [with left axis deviation (LAD); 14 and without LAD; 19] and left bundle branch block (LBBB) pattern in 24 patients. IRVT was significantly high in RBBB with LAD (92.9%) compared with RBBB (63.6%), RBBB without LAD (42.1%) and LBBB (37.5%). Both cardiothoracic ratio and ejection fraction had no relationship to IRVT. PMID- 1916627 TI - [A population study of long-term salt restriction in mild hypertensives]. AB - We all agree to the importance of the salt restriction in the prevention and the treatment of hypertension. But it is not easy to teach the way to reduce salt intake in each person or patient. And we also not confident that how long could they maintain the low salt diet. In this study we investigate following problems, 1) Can the salt intake be reduced in public population? 2) Can blood pressure be lowered by reducing salt intake in mildly hypertensive individuals? 3) If the desired changes are obtained, can they be preserved for a long time? and 4) Are there any difference in the amount of the salt intake between hypertensives and normotensives? One hundred and forty subjects from 23,940 people in whom borderline to mild hypertension was found at group medical examinations in each district, where a total of 29,940 people were examined, were registered to a educational course of new salt-restriction program. Salt intake was estimated from salt measurement in 24-hour urine samples. Educational program was composed of many lectures, sampling party and individualized consultations about dietary problems, using an original dietary questionnaire list. The results were as follows: In short-term (2.5 months) after the initial education, sodium intake reduced from 235.1 +/- 110.8 mmol/day to 161.4 +/- 85.0 mmol/day (p less than 0.001). The systolic and diastolic blood pressure also fell significantly in borderline hypertensives (from 148 +/- 7/87 +/- 5 mmHg to 141 +/- 12/85 +/- 7 mmHg, p less than 0.001) and hypertensives (from 165 +/- 13/99 +/- 8 mmHg to 157 +/- 15/95 +/- 8 mmHg, p less than 0.001) but they did not change in normotensives (from 133 +/- 6/80 +/- 6 mmHg to 131 +/- 9/82 +/- 8 mmHg). In long-term (range from 12 to 36 months) observation, low salt diet (167.6 +/- 72 mmol/day) and a fall in blood pressure were also maintained in borderline (142 +/- 2/85 +/- 7 mmHg, p less than 0.001) to hypertensive population (156 +/- 14/93 +/- 8 mmHg, p less than 0.001), and in the normotensive population, no change in blood pressure was observed (134 +/- 13/82 +/- 9 mmHg). Hypertensives tended to show higher sodium intake than normotensives (206 +/- 101 mmol/day vs. 199.0 +/- 96, p less than 0.005), and also show higher sodium/potassium ratio than normotensives and borderline hypertensives (4.3 +/- 2.3 vs. 3.6 +/- 1.6 and 3.8 +/- 1.8, p less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1916628 TI - [The inductive effect of interleukin 4 on IgG4 and IgE synthesis in human peripheral blood lymphocytes]. AB - Using murine monoclonal antibodies against human IgG subclasses, specific and sensitive enzyme-linked immunosorbent assay to quantitate the four human IgG subclasses in cell culture supernatants were established. The effect of human recombinant interleukin-4 (IL4) on the synthesis of IgG subclasses by normal peripheral blood lymphocytes was investigated. The IL4 preferentially induced IgG4 synthesis and IgE as well in vitro, whereas it had no effect on IgG1, IgG2 and IgG3 synthesis. The IL4-induced IgG4 and IgE production was inhibited in a dose-dependent manner by recombinant interferon-gamma and anti-human IL4 monoclonal antibody, respectively. Collectively, these data indicate that IL4 plays an important regulatory role in both IgG subclass and IgE synthesis. PMID- 1916629 TI - [Synthesized leukotoxin: its biological activity and establishment of radioimmunoassay]. AB - Leukotoxin, 9: 10-epoxy-12-octadecenoic acid, was reported to exist in human burned skin and neutrophils, and to have toxic effects in experimental animals and antifungal effects against rice blast disease. Leukotoxin was regarded as a toxic and/or defensive substance in living beings. The author synthesized leukotoxin from linoleic acid with peracetic acid and purified practically by thin layer chromatography. The leukotoxin synthesized was injected into guinea pigs intravenously and caused a systemic convulsion of the animal body and cardiac arrest. The leukotoxin synthesized, on the other hand, was conjugated with bovine serum albumin (BSA) by means of the mixed anhydride technique and immunized in rabbits. After immunization of leukotoxin conjugated with BSA over 4 months, the author succeeded in producing anti-leukotoxin antiserum for the first time. According to a titration test of antiserum, sixty-folds diluted antiserum was found to bind approximately 50% of methylated leukotoxin labeled with carbon 14. And unlabeled leukotoxin was detected at least 5 ng in this radioimmunoassay by use of polyethylene glycol precipitation. This antiserum had a strong specificity to leukotoxin and no cross-reactivity to the other analogs tested. The role of leukotoxin in living creatures had not been clarified yet. Therefore both the leukotoxin synthesized by this simple procedure and the anti-leukotoxin antibodies would aid the study of the mechanism of its biological activities and its histochemical investigations. PMID- 1916630 TI - [HTLV-I tax mediated activation of cellular genes in transgenic mice]. AB - The tax protein of human T-cell leukemia virus type I (HTLV-I) is known to be a potent transactivator of its own long terminal repeat (LTR) promoter and the cellular genes (IL-2, IL-2R, c-fos and GM-CSF). These effects of tax have been studied in vitro, mostly in T-cell lines. To determine its function in vivo in multiple cell types, we have used two transgenic mouse lines in which tax is expressed under the control of the LTR (LTRtax) or murine Thyl. 2 (Thytax) transcriptional regulatory sequences. Tax protein is expressed in fibroblasts, salivary gland, skeletal muscle, bone matrix and thymus tissue. In these tissues the expression of endogenous IL-2R, c-fos, GM-CSF, Zif268, IL-6, and PDGF-B were studied. In fibroblastic tumors GM-CSF, IL-6, PDGF-B, Zif268, c-fos were expressed at high levels. No significant changes in expression of these genes were seen in other tissues. This suggests that tax mediated transcriptional transactivation alone is not sufficient to cause accumulation of these cellular gene products. Other events which occur during tax mediated transformation in vivo allow high levels of cellular gene expression constitutively. PMID- 1916631 TI - [Behavioral and neuropathological analyses of rats with intrahippocampal lesions]. AB - Rats with intrahippocampal lesions produced by infusion of colchicine showed an impairment of learning ability and a decrease in local choline acetyl-transferase activity. In addition, these rats showed bizarre excitable behavior from 3 days after infusion for about an average of 10 days. This included daytime arousal, and easy jumping and squeak reactions against external stimuli as compared to the sham-operated control rats. Moreover, three-dimensional behavioral analysis disclosed: (i) the lesioned rats showed an increase ambulation compared to the control rats, (ii) a more centrally oriented sequence of wandering, while the control rats tended to display peripheral movement around the wall of the test cage, and (iii) they showed a decrease movement associated with rearing compared to the control rats. Neuropathologically, pyramidal neurons and fascia dentata of the lesioned hippocampus showed degeneration from 3 days with a marked astrocytic reaction. In addition, transient over expression of synaptophysin-immunoreactive material was seen in early stage of degeneration and this corresponded ultrastructurally to the presence of swollen synaptic boutons containing numerous non-core synaptic vesicles. These findings appeared to represent in part an abnormal excitement seen in patients with organic brain lesions, in which the excitement has been considered to correspond with neuronal death. Thus, the hippocampus-lesioned rats may provide an animal model to analyse the abnormal behaviors associated with neuronal death. PMID- 1916632 TI - [A case of type B chronic hepatitis showing rapid progression to liver cirrhosis with prolonged positive IgM anti-HBc]. AB - We reported a case of type B chronic hepatitis with high titer of IgM anti-HBc continuously, which progressed to liver cirrhosis rapidly. The patient was a 37 years-old man, and was diagnosed as chronic type B hepatitis with severe activity by laparoscopy and liver biopsy. The titer of IgM anti-HBc persisted high level for more than 2 years. Then the second liver biopsy showed the progression to liver cirrhosis within only about 2 years. It is a very rare case to prolong positive IgM anti-HBc for such a long time. Anti-HBc production of PBMC was enhanced remarkably in this case. We considered that HBc antigens released into serum from hepatocytes with severe exacerbations had enhanced the anti-HBc producing activity of B lymphocytes. And the rapid progression in this case would be due to the episodes of severe exacerbations. PMID- 1916633 TI - A role for beta-endorphin in the pathogenesis of human obesity? AB - The discovery of several endogenous substances with morphine-like activity (endorphins and enkephalins) which possess potent behavioral effects, interfering with food and water intake, has led to suggest their implications in the pathogenesis of human obesity. This suggestion is mainly based on: 1) the ability of opiate antagonists naloxone and naltrexone to reduce food intake in some particular situations associated with obesity: 2) the existence of raised plasma levels of beta-endorphin in obese children and adults not corrected by weight loss; and 3) the increased responsiveness to the metabolic and hormonal effects of opiate agonism and antagonism found in obese but not in normal weight subjects. Although the problem still awaits a definite answer, it seems not hazardous to hypothesize a role for beta-endorphin in some pathogenetic events associated with human obesity. PMID- 1916635 TI - Secretion and elimination of insulin by the in vitro perfused pancreas and liver of rats with thioacetamide-induced liver cirrhosis. AB - Pancreatic secretion and hepatic removal of insulin have been measured in thioacetamide (TAA)-induced compensated rat liver cirrhosis in perfusion experiments. Peripheral plasma concentrations of glucose and insulin were slightly decreased in TAA-treated rats. Pancreatic secretion and hepatic removal of insulin remained unchanged by the TAA-treatment. Thus, even in morphologically and biochemically proven experimental liver cirrhosis, insulin secretion and removal may not be disturbed. PMID- 1916634 TI - Attenuated anomeric difference of glucose-induced insulin release in the perfused pancreas of diazoxide-treated rats. AB - Mild hyperglycemia was induced in normal rats by oral administration of both diazoxide and D-glucose. After 48 hours of such a treatment, the insulin and glucagon secretory responses of the perfused pancreas to alpha- and beta-D glucose (3.3 mM) were examined in the presence of 10.0 mM L-leucine. The output of insulin, but not that of glucagon, and the perfusion pressure were higher in treated than control rats. The alpha-anomer of D-glucose was a more potent insulin secretagogue than beta-D-glucose in both control and treated rats. However, the alpha/beta ratio in insulin output was twice higher in control than treated rats. By analogy with other experimental models of diabetes, the attenuation in the anomeric difference of glucose-stimulated insulin output in the treated rats could reflect an altered secretory response to alpha- rather than beta-D-glucose. These findings suggest that hyperglycemia provokes, as a function of its severity and duration, first attenuation and then suppression, if not inversion, of the anomeric preference for alpha-D-glucose in insulin release. They are also compatible with the hypothesis that the anomeric malaise, associated with B-cell glucotoxicity, is caused by a progressive accumulation of glycogen in this cell. PMID- 1916636 TI - Diacylglycerols modulate insulin action in rat adipocytes. AB - Effect of 1,2-diacylglycerols on the insulin receptor function and insulin action in rat adipocytes was studied. 1,2-dioctanoylglycerol (100 micrograms/ml) did not alter insulin binding but it did stimulate phosphorylation of the beta-subunit of the insulin receptor as well as its tyrosine kinase activity. However, dioctanoylglycerol inhibited insulin-stimulated receptor autophosphorylation. This concentration of dioctanoylglycerol inhibited insulin-stimulated CO2 metabolism, lipogenesis and 3-O-methyl-glucose transport in a dose-dependent manner but did not alter any of these bioeffects in absence of insulin. While there was no direct link between diacylglycerol effect on tyrosine kinase activity of the insulin receptor and insulin action in rat adipocytes, the parallel inhibition of insulin-stimulated receptor autophosphorylation and insulin bioeffects by dioctanoylglycerol suggests its direct or indirect role in insulin signalling in rat fat cells. PMID- 1916637 TI - Insulin binding to skeletal muscle microsomes in lactating and dry sheep. AB - Microsomes were prepared from skeletal muscles taken from lactating and non lactating ewes. Insulin binding to these microsomes was not affected by reproductive status. There were significant differences in the ability of individual muscles to bind insulin. These differences correlated with the function of the muscle, as defined by the predominant muscle fibre type. PMID- 1916638 TI - Glucose reduces PDGF production and cell proliferation of cultured vascular endothelial cells. AB - The effect of glucose on PDGF production and cell proliferation was studied on cultured bovine aortic endothelial cells. PDGF levels were measured using an enzyme-linked immunosorbent assay technique newly developed in our laboratory. The cell proliferation rate was determine on the basis of 3H-thymidine incorporation into cellular DNA. PDGF levels in culture medium were below the detection limit of the assay. However, PDGF levels were measurable in cultured endothelial cells at confluence. Both PDGF production and thymidine incorporation were significantly reduced in the endothelial cells cultured with high concentrations of glucose. These results suggest that reduced PDGF production and cell proliferation may be involved in altered vascular endothelial function in diabetics. PMID- 1916639 TI - Relation between blood plasma viscosity and presence of vascular and neurological complications in diabetic Africans. AB - The relation between changes in plasma and serum viscosity and the presence of diabetic vascular and neurological complications was investigated in 50 diabetic Africans. Diabetics with complications had significantly elevated plasma and serum viscosity compared with those of both diabetics without complications and healthy non-diabetics. Hypertension also contributed to the elevation of plasma and serum viscosity in diabetics with complications. Plasma and serum viscosity of diabetics significantly correlated with the number of vascular and neurological complications. Diabetics with cerebrovascular disease had the highest plasma and serum viscosity due to the presence of many complications. The results of this study suggest that changes in plasma and serum viscosity may be associated with abnormalities of vascular and neurological function present in diabetic Africans. PMID- 1916640 TI - The binding of different biosynthetic and extracted human growth hormones to the growth hormone-binding protein of human serum: a comparative study. AB - This study of the human growth hormone binding protein (GHBP) was undertaken using several samples of hGH, extractive or recombinant, from different origins. They were labelled in identical conditions and assayed by gel chromatography after incubation with three human sera having different levels of binding activity. For each serum the binding activities of the five recombinant hormones were very close and significantly higher (P less than 0.005) then the binding activities of the 2 extractive hormones. A radioactive peak which appeared in the zone of high molecular weights was more important with extractive than with recombinant hormones (P less than 0.01). This peak increased with the ageing of the tracer and appeared even when the tracer was incubated in the absence of serum. Thus, it is for its main part not related to another binding protein but, more likely, to a polymerization of the hormone. These data point out the importance of accurate technical conditions to have a reproducible assay for GHBP and to interpret the results in studies of growth disturbances. PMID- 1916641 TI - N-acetyl-beta-glucosaminidase and albuminuria in acromegaly. AB - Significantly increased albuminuria and N-acetyl-beta-glucosaminidase activity in serum and urine have been observed in acromegalic patients in comparison with healthy persons (P less than 0.001). No relationship between these biochemical variables and serum growth hormone or insulin concentration was found in our group of patients. Significant correlation was determined between urinary NAG activity and albuminuria of acromegalic patients (r = 0.84). PMID- 1916642 TI - Insulin sensitivity in patients with primary hyperparathyroidism before and after parathyroidectomy: sequential euglycemic insulin clamp studies. PMID- 1916644 TI - An effect of prolactin on K uptake by lactating rat mammary tissue. PMID- 1916645 TI - Cardiac and plasma catecholamine responses to exercise in patients with hyperthyroidism. PMID- 1916643 TI - Presence of glucagon-containing peptides in a human pancreatic glucagonoma and its liver metastasis. PMID- 1916646 TI - Impact of the perfluorochemical FC43 on function of isolated islets: a preliminary report. PMID- 1916647 TI - Analysis of low molecular mass GTP-binding proteins in insulinoma-derived RINm5F cells by two-dimensional gel electrophoresis. PMID- 1916648 TI - Multicenter clinical trial to evaluate the therapeutic use of recombinant growth hormone from mammalian cells in the treatment of growth hormone neurosecretory dysfunction. AB - The efficacy and safety of a 12-month treatment with recombinant human growth hormone from mammalian cells (r-hGH, Saizen) in growth hormone neurosecretory dysfunction (GHND) are evaluated in this study. r-hGH was administered subcutaneously, at a dosage of 0.5 IU/kg/week divided into 6 equal daily doses. A total of 16 (12 M and 4 F) poorly growing patients, height -2.3 SD or more below the mean for chronological age and sex, were included in the study. r-hGH therapy significantly increased the growth velocity; from 3.57 +/- 0.85 cm/year, before therapy, to 7.09 +/- 2.29 cm/year after 12 months (p less than 0.001). Patients' height SD score rose from -3.40 +/- 0.84 SDS to -2.98 +/- 0.69 SDS (p less than 0.01). Somatomedin C increased significantly from a baseline value of 0.59 +/- 0.32 U/ml to 1.26 +/- 0.66 U/ml after therapy (p less than 0.01). Finally, r-hGH therapy improved the pretreatment adult height prediction; from an initial prognosis of -2.66 +/- 0.79 SDS to -2.17 +/- 0.81 SDS after treatment (p less than 0.01). No side effects or adverse reactions were observed during treatment. Anti-r-hGH antibody formation was not found in any of the patients included in the study. PMID- 1916650 TI - Evaluation of 24-hour growth hormone spontaneous secretion: comparison with a nocturnal and diurnal 12-hour study. AB - Spontaneous growth hormone (GH) secretion in 116 short children was studied by sampling blood for GH measurement every 20 min over 24 h. We calculated 24-h mean GH concentration (MGHC), diurnal 12-h MGHC (dMGHC) and nocturnal 12-h MGHC (nMGHC). The children were subdivided into four groups: prepubertal children with 'classical' GH deficiency (group 1, n = 12, low responses to two provocative stimuli tests and MGHC less than 3 ng/ml), prepubertal children with 'nonclassical' GH deficiency (group 2, n = 36, normal GH responses to two provocative tests and MGHC less than 3 ng/ml), short normal children (normal GH responses to two provocative tests and MGHC greater than 3 ng/ml) at stage P1 of puberty (group 3, n = 41) and at stage P2 of puberty (group 4, n = 27). The values of MGHC, dMGHC and nMGHC were significantly higher in groups 3 and 4 than in groups 1 and 2, and in group 4 than in group 3. The values of MGHC and nMGHC were significantly higher in group 2 than in group 1. MGHC correlated highly with nMGHC and dMGHC (r = 0.97 and 0.94, respectively; p less than 0.001). On the basis of regression equations between MGHC and nMGHC or dMGHC, the study of the diagnostic accuracy showed values higher for nMGHC than for dMGHC: 94.1 vs. 89.6% for sensitivity, and 93.7 vs. 89.7% for specificity, respectively. PMID- 1916649 TI - Exogenous human growth hormone reduces body fat in obese women. AB - The effects of biosynthetic methionyl human growth hormone (met-hGH) on body composition and endogenous secretion of insulin-like growth factor I (IGF-I) were studied in obese women ranging between 138 and 226% of ideal body weight. Following double-blind procedures, 12 subjects were assigned at random to either treatment with met-hGH (n = 6, 0.08 mg/kg desirable body weight) or placebo (n = 6, bacteriostatic water diluent). Treatments were delivered intramuscularly three times per week for a period of 27-28 days. Subjects were instructed to follow a weight-maintaining diet and their pre- and posttreatment kilocaloric intake was monitored for verification. The baseline peak serum GH response to L dopa/arginine stimulation for the study population as a whole, was in the hyposecretory range (9.6 +/- 1.9 ng/ml), accompanied by a low level of circulating IGF-I (0.56 +/- 0.09 U/ml). Hydrodensitometry revealed that the met hGH-treated subjects had a significant reduction in body fat, while an observed mean increase in fat-free mass (FFM) approached significance. The percent change in body fat was unrelated to pretreatment levels of body fat, total body weight, or initial endogenous GH status. Changes in circulating IGF-I were similar to those for FFM, with increases approaching significance. There were no significant changes in body composition or IGF-I in the placebo-treated subjects. No significant differences were observed in the self-reported dietary intake of kilocalories during the experimental period between the two groups. We conclude that exogenous GH reduces body fat in obese women in the apparent absence of significant kilocaloric restriction. The effect appears to be unrelated to endogenous GH secretion or body composition. PMID- 1916652 TI - Evidence of altered dopaminergic modulation of prolactin and thyrotropin secretion in patients with polycystic ovary syndrome. AB - In order to evaluate the functional activity of the tubero-infundibular dopaminergic system in polycystic ovary syndrome (PCOS), we analysed the prolactin (PRL) and thyrotropin (TSH) responses to the dopamine antagonist sulpiride. We studied 8 euthyroid women affected by PCOS and 7 normal women. The mean baseline PRL values were normal in both groups. After sulpiride administration the incremental area under the PRL profile in PCOS was significantly lower than in normal subjects (p less than 0.01). The mean basal plasma TSH levels were significantly higher in the PCOS than in the control group (p less than 0.01). After sulpiride administration the incremental area under the TSH profile was significantly lower in PCOS patients than in normal women (p less than 0.01). The higher basal plasma levels of TSH, the blunted response of PRL and the lack of response of TSH to sulpiride in PCOS suggest a relative decrease of the dopaminergic activity in PCOS patients. PMID- 1916651 TI - Nocturnal profile of growth hormone secretion during sleep induced by zolpidem: a double-blind study in young adults and children. AB - Overnight blood sampling for repeated growth hormone (GH) assays, regarded as the most physiological assessment of GH status, may induce some disturbances in patients' sleep and then in the evaluation of GH secretion. We studied the influence of a hypnotic drug, zolpidem (10 mg), on nocturnal GH profiles (GH peak, time to first and maximum GH peak, area under the curve, mean integrated concentration) over two nights at a 7-day interval, in a double-blind cross-over design in a group of 12 young adult volunteers (27.9 +/- 4.3 years), and in a group of 12 children (10.8 +/- 2.3 years) with short stature, in a parallel double-blind study. Mean GH profiles showed no difference between zolpidem treated subjects and placebo-treated controls, either in adults or in children. Although in these experimental conditions, sleep onset latency was significantly reduced with zolpidem in the adult volunteers, the mean time to first GH peak remained unchanged. Furthermore, GH profile did not relate with sleep duration, sleep onset latency or number of awakenings. A hypnotic drug, such as zolpidem, given at bedtime, is therefore devoided of effect on nocturnal GH profile and may be used in young children for overnight blood sampling when needed. PMID- 1916653 TI - Congenital hypothyroidism and pericardial effusion. AB - A group of infants, affected by congenital hypothyroidism diagnosed through the neonatal screening program, was investigated with echocardiography to detect the presence of pericardial effusion. We studied the relationship between the effusion and the etiology of hypothyroidism, established through thyroid scintiscanning. Our data show a high prevalence of effusion in hypothyroid patients, without other clinical signs of cardiac involvement as well as a relationship between the etiology of hypothyroidism and the presence of effusion. This seems to be much more frequent in those forms which can imply a more severe hormonal defect, particularly during fetal life (agenesis/dyshormonogenesis). Furthermore, the high prevalence of pericardial effusion suggests to start the L T4 replacement therapy with lower dosages as commonly advised, in order to avoid a cardiac involvement. PMID- 1916655 TI - 17th annual meeting of ISGD. Williamsburg, Va, June 19-22, 1991. Abstracts. PMID- 1916654 TI - Dynamic changes in soluble interleukin-2 receptor levels during treatment of Graves' disease. Correlation with disease activity. AB - The activation of T lymphocyte is accompanied by the release of soluble interleukin-2 receptors (sIL-2R) which can be assessed in biological fluids. A prospective study of the dynamic changes in sIL-2R levels was performed in the serum of 10 patients undergoing a medical treatment for Graves' disease. All patients received carbimazole during the study and, when necessary, L-thyroxine to compensate hypothyroidism. sIL-2R levels were measured before (M0) and after the 1st (M1), 3rd (M3) and 6th month (M6) of treatment. The levels of sIL-2R were high at M0 and M1, and decreased significantly between M1 and M3 (p = 0.03). At M0, the levels of sIL-2R were highly correlated with triiodothyronine (T3) levels (p = 0.0003), early [131I] uptake (p = 0.007) and, to a lesser degree, with anti thyrotropin receptor antibody levels (p = 0.02). At M6, no correlation was found anymore. We conclude that sIL-2R levels are increased in patients with untreated Graves' disease. They are highly correlated with the markers of Graves' disease activity and decrease during medical treatment. PMID- 1916656 TI - Association of pharmacological tests and study of 24-hour growth hormone secretion in the investigation of growth retardation in children: analysis of 257 cases. AB - Growth hormone (GH) secretion can presently be investigated by several methods: pharmacological provocative tests, study of 24-h GH secretion, measurement of somatomedin-C (Sm-C)/insulin-like growth factor (IGF) I, and the growth hormone releasing hormone (GHRH) test. In order to compare the results obtained, these methods were used in 257 children with growth retardation (169 boys, 88 girls). Their height SD was -2.7 +/- 0.2, chronological age 11 3/12 +/- 1 6/12 years, and bone age 8 4/12 +/- 1 4/12 years. Mean growth velocity was 4.5 +/- 1.5 cm/year. One hundred and thirty-eight boys and 80 girls were prepubertal, and 31 boys and 8 girls were pubertal (B2 G2). All children underwent the study of 24-h GH secretion (n = 257) and pharmacological provocative tests (two tests, n = 213; one test n = 44). Sm-C/IGF I was measured in prepubertal children (n = 131), and a GHRH test was carried out (n = 153). In addition, the mean integrated concentration of growth hormone secretion (IC-GH) was assessed in a control group of 23 children and was found to be 5.4 +/- 1.2 ng/ml/min. The IC-GH in the group as a whole was 2.6 ng/ml/min. The mean maximum peak during pharmacological tests varied considerably according to the test used, ranging from 7.8 ng/ml for the arginine test to 17.1 ng/ml for the glucagon and betaxolol test. The maximum peak and the 24-h IC-GH were not significantly correlated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916657 TI - Comparative study of biosynthetic human growth hormone immunogenicity in growth hormone deficient children. AB - The immunogenicities of six recombinant human growth hormone (rhGH) preparations, from KABI (A rhGH191 and B rhGH192), Eli Lilly (C), Nordisk (D), Sanofi (E) and Serono (F), used to treat 260 GH-deficient children, have been compared using a common specific and sensitive procedure for antibody determination. For this purpose we developed two immunoassays: a competitive liquid radioimmunoassay using 125I-rhGH, and an immunometric solid enzymoimmunoassay in which the rhGHs were immobilized. Blood samples were collected from the GH-deficient children before treatment and after 3, 6, 9, 12, 18 and 24 months of therapy. Human GH antibodies were detected in children treated with 3 of the 6 rhGH preparations. Seven percent of the patients treated with hormone A, 14% with hormone B and 22% with hormone C formed antibodies against the respective rhGH. Differences in capacity and affinity of the hGH antibodies were observed between these anti-GH positive groups. They could be divided into 2 groups according to their immunopotency. One group (7, 14 and 6% of the patients treated with hormones A, B and C, respectively) developed anti-hGH antibodies with very low binding capacities (30-100 fmol/ml). The other group (16% of the patients treated with hormone C) developed IgG-type antibodies to hGH with higher binding capacities (200-1,200 fmol/ml) and a measurable binding affinity (Ka = 10(8) M-1). These hGH antibodies partially inhibited the binding of labeled GH to its specific liver membrane receptor. However, because of their low titer, they did not inhibit growth in the treated children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916658 TI - Sodium valproate-induced menstrual disturbance in young women. AB - Two young girls with epilepsy presented with menstrual disturbances whilst on treatment with sodium valproate. On withdrawing valproate therapy, period cyclicity returned to normal in both individuals. An exaggerated luteinising hormone response to parenterally administered gonadotropin-releasing hormone was present in both subjects. The temporal relationship between normalisatin of periods and stopping the sodium valproate suggests that this drug may possibly affect the control of the menstrual cycle through a GABAergic mechanism. PMID- 1916659 TI - Papillary carcinoma in an ectopic thyroid. AB - Ectopic thyroid tissue can be seen anywhere from the foramen caecum to the lower neck. Most frequently it presents as a thyroglossal duct cyst associated with a normal thyroid gland. Less common is total ectopia, which can occur as a lingual thyroid or occasionally in non-lingual locations. Malignant transformation of such ectopic tissue is extremely uncommon. Only 21 cases of lingual thyroid carcinomas have been reported until 1971. We present, to our knowledge, the first case of a papillary carcinoma in a non-lingual ectopic thyroid in the absence of an orthotopic thyroid. PMID- 1916660 TI - Hepatorenal reflex regulating kidney function. AB - In anesthetized male rats, infusion of glutamine (2 mumol/min) into the superior mesenteric vein at a rate known to induce liver cell swelling leads to marked decreases in renal glomerular filtration rate, renal para-aminohippurate clearance and urinary flow rate. Glutamine infused at identical rates into the jugular vein does not elicit any of these effects. The effect of glutamine is mimicked by serine but not by glutamate. Spinal transection, renal denervation or section of the vagal hepatic nerves abolishes the effect of mesenteric venous glutamine infusion. Mesenteric application of glucagon (1 ng/min) or of both glutamine and glucagon enhances glomerular filtration rate and urinary flow rate. Infusion of 1 ng/min glucagon through the jugular vein does not significantly alter glomerular filtration rate or urinary flow rate. The data disclose a powerful liver-borne mechanism regulating kidney function that is mediated by the hepatorenal innervation. PMID- 1916661 TI - Estrogen and progesterone receptors in the gallbladders from patients with gallstones. AB - Cytosolic receptors for estrogen and progesterone were assayed in 50 gallbladders from 29 women and 21 men who had cholecystectomies because of cholelithiasis. High-affinity (equilibrium dissociation constant, KD = 0.46 +/- 0.23 nmol/L of 24 cases) estrogen receptors were detected in 20 of 29 gallbladders from women (range = 1.6 to 32 fmol/mg protein; mean +/- S.D. = 10.9 +/- 8.1), whereas in men only 4 of 21 specimens contained detectable estrogen receptors. High-affinity (KD = 0.45 +/- 0.17 nmol/L; mean +/- S.D. of 41 cases) progesterone receptors were found in 25 of 29 gallbladders of women (range = 2 to 62 fmol/mg protein; mean +/ S.D. = 19.2 +/- 14.4) and in 16 of 21 gallbladders of men (range = 4 to 36 fmol/mg protein; mean +/- S.D. = 12.5 +/- 8.5). There is a statistically significant difference between men and women in the proportion of estrogen receptor-positive gallbladders, 19% and 69% for men and women, respectively. Progesterone receptors are present in similar proportion in the gallbladders of men (72.2%) and women (86.2%). In women a positive correlation between estrogen and progesterone receptors was found. Even in the absence of estrogen receptors, the gallbladders of men express progesterone receptors at levels similar to those observed in women. At least in cholelithiasic gallbladders, this suggests that a sex difference exists in the coexpression of estrogen and progesterone receptors. Such a difference could be related with the higher gallstone incidence in women than in men. PMID- 1916662 TI - Bone loss after liver transplantation. AB - We studied 35 adult patients (mean age = 43 yr) referred for orthotopic liver transplantation. Spinal bone mineral density was measured by quantitative computed tomography scanning before transplantation (n = 35) and at 3 mo (n = 21) and 12 mo (n = 11) after orthotopic liver transplantation. The readings were corrected to age 50 yr, using the regression equations derived from normal control subjects. Quantitative bone histological studies were performed in 17 patients before orthotopic liver transplantation and 3 mo after orthotopic liver transplantation. Before orthotopic liver transplantation, the corrected spinal bone mineral density in men was 108 +/- 20 mg/cm3, less than in male control subjects (129 +/- 22 mg/cm3, p less than 0.005). In women patients the value was 117 +/- 27 mg/cm3, and in female control subjects 126 +/- 19 mg/cm3 (NS). However, women patients with primary biliary cirrhosis had lower spinal bone mineral density (106.5 +/- 14.8) than female control subjects (p less than 0.005). Histologically, the resorbing surface was near the normal mean, whereas the osteoblast surface, tetracycline surface and bone formation rate was lower in men (p less than 0.05) but not women. Spinal bone mineral density decreased by 24% in the first 3 mo after orthotopic liver transplantation with no further decrease at 12 mo. Five patients had vertebral fractures within 6 mo of orthotopic liver transplantation. One patient fractured a wrist and three had osteonecrosis of the hip or knee.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916663 TI - Hepatic activity and mRNA expression of aspartate aminotransferase isoenzymes in alcoholic and nonalcoholic liver disease. AB - In liver and serum, AST activity is dependent on two isoenzymes, which are mitochondrial and cytosolic in nature. In an attempt to explain the well-known increase of serum mitochondrial AST-to-total AST ratio in chronic alcoholism (which is due to a specific increase of the mitochondrial isoenzyme), we analyzed: (a) liver and serum AST, ALT and glutamate dehydrogenase activities in 23 active drinkers with minimal liver changes, 11 alcoholic patients with cirrhosis who had stopped drinking, 18 nonalcoholic patients with viral chronic hepatitis and 11 subjects with normal livers; and (b) the expression of messenger RNAs for AST isoenzymes in the corresponding liver samples. Enzymatic activities were decreased in the liver irrespective of the origin of the liver disease. In patients with viral chronic hepatitis (or in those with alcoholic cirrhosis when abstinent), variations in liver proteins and messenger RNAs paralleled significant decreases in mitochondrial AST, ALT and glutamate dehydrogenase and a nonsignificant decrease of cytosolic AST. In alcoholic patients with minimal liver changes, the significant decrease of hepatic cytosolic AST, ALT and glutamate dehydrogenase activities contrasted with a close-to-normal liver mitochondrial AST activity; the increased amounts of mitochondrial AST messenger RNA give evidence for a pretranslational mechanism of regulation, indicating a possible increase in the total production of mitochondrial AST in the liver. The decrease of hepatic cytosolic AST activity was statistically significant only in alcoholic patients without cirrhosis who had a normal cytosolic AST mRNA level, thus suggesting a contributory role of translational or posttranslational regulation. In conclusion, regulation of AST isozymes during liver disease is complex, including differential, pretranslational and translational or posttranslational mechanisms. PMID- 1916664 TI - Extracellular ATP, intracellular calcium and canalicular contraction in rat hepatocyte doublets. AB - Bile-canaliculus contraction in rat hepatocyte doublets is postulated to involve activation of an actin-myosin system. We examined this hypothesis by determining the relationship between canalicular contraction and cystolic free Ca2+ ([Ca2+]i) concentration after extracellular addition of ATP or microdialysis of myosin light chain kinase or its Ca(2+)-independent fragment, which retains catalytic activity. After incubation of doublets with 200 mumol/L ATP in the absence of extracellular Ca2+, [Ca2+]i peaked at 40 sec and 71% of canaliculi contracted within 4 min. Decreasing effects were observed with equimolar ADP, AMP and nonhydrolyzable ATP, but no effect was observed with adenosine. The effect of extracellular ATP on [Ca2+]i and canalicular contraction was dose dependent. Addition of extracellular Ca2+ and ATP resulted in a plateau level of [Ca2+]i. Cytochalasin D, which depolymerizes actin filaments, inhibited ATP-induced canalicular contraction, but not the increase in [Ca2+]i. Microdialysis of myosin light chain kinase and its Ca(2+)-independent fragment (but not the heat denatured fragment, albumin, trypsin plus soybean inhibitor or buffer) into one hepatocyte of a doublet resulted in canalicular contraction in 86% of doublets. Injection of myosin light chain kinase or its Ca(2+)-independent fragment did not increase [Ca2+]i within 5 min. These results indicate that (a) the basolateral plasma membrane of hepatocytes has a P2Y-class purinoceptor, (b) increased [Ca2+]i after incubation with ATP is initially due to mobilization from internal sites and (c) canalicular contraction is directly related to [Ca2+]i and activation of an actin-myosin system. The physiological role of extracellular ATP in canalicular contraction is uncertain. PMID- 1916666 TI - ATP-dependent taurocholate transport by rat liver canalicular membrane vesicles. AB - We conducted an experimental study to examine the possibility that ATP is involved in the mechanism by which bile acids are excreted through the liver canalicular membrane in opposing the concentration gradient. Canalicular membrane vesicles were purified from the livers of Sprague-Dawley rats, and the uptake of tritiated sodium taurocholate into canalicular membrane vesicles was determined by rapid filtration technique. Vesicle-associated sodium taurocholate was increased in the presence of ATP and ATP-regenerating system. This was also observed at a voltage-clamped condition. ATP-dependent uptake into the osmotically reactive intravesicular space was saturated with increasing concentrations of sodium taurocholate (Km = 47 mumol/L, Vmax = 270 pmoles/mg protein.20s). ATP-dependent uptake increased to the point of saturation when the sodium taurocholate concentration was 50 mumol/L and the ATP concentration was increased from 0 to 1 mmol/L (Km = 64 mumol/L). Among the several nucleotides used, ATP was a potent stimulator of transport, whereas a nonhydrolyzable analogue (i.e., adenosine 5'-[beta,gamma-imino]triphosphate) showed no effect. In addition, ATP-dependent transport was inhibited by vanadate in a dose-dependent manner. From these results it was concluded that the primary active transport of sodium taurocholate is present in hepatocellular canalicular membranes. This transport is directly dependent on ATP, and hydrolysis of gamma-phosphate of ATP is required. PMID- 1916665 TI - Role of extracellular zinc and copper on metallothionein regulation in cultured rat hepatocytes. AB - Cellular and extracellular metallothionein contents of rat hepatocytes cultured in the presence of albumin (30 mumol/L) with zinc (1, 10, 50 and 100 mumol/L), copper (1, 10 and 50 mumol/L), zinc and copper (1, 10 and 50 mumol/L of each metal) or no metals in the culture medium have been measured by radioimmunoassay. Cellular metallothionein levels increased steadily with culture time regardless of the metal treatment and showed little dependence (only a twofold increase) on extracellular zinc or copper at all metal concentrations and times (up to 3 days) studied. In contrast, the presence of both metals simultaneously in the culture medium strongly increased cellular metallothionein contents, acting synergistically in some cases. Significant extracellular metallothionein was observed when copper or zinc and copper were present in the culture medium, most of which is likely a consequence of cell leakage because no evidence of physiological secretion was observed. Total metallothionein production (cellular and extracellular metallothionein levels) indicated that copper was a better metallothionein inducer than zinc in these experimental conditions. These results indicate that metallothionein regulation in the hepatocyte is different depending on the extracellular metal levels and composition and that attention must be given to metallothionein release from the hepatocyte. PMID- 1916667 TI - The effect of capsaicin on gallbladder fluid absorption. AB - The role of the enteric nervous system of the gallbladder on mucosal water absorption was evaluated by intraluminal administration of capsaicin, a selective stimulant of afferent nerve endings. It has been postulated that the neural responses of the gallbladder are peptidergic and mediated by prostanoids. Anesthetized cats underwent gallbladder perfusion with a physiological buffer solution containing 14C polyethylene glycol as a nonabsorbable tracer to quantitate mucosal water absorption. Capsaicin was added to the perfusate and administered intraluminally at a rate of 5 mg/kg-1/hr-1 for 2 hr. One experiment on five cats was performed when capsaicin was administered and five control experiments were performed when only vehicle was added to the perfusate. Five experiments were performed when indomethacin was administered intravenously (5 mg/kg-1/hr-1) and buffer solution alone was used to perfuse the gallbladder, and five experiments were performed when capsaicin was added to the perfusate and indomethacin was administered intravenously. Additional experiments were performed when lidocaine was added to the perfusate and when lidocaine and capsaicin were administered simultaneously. Gallbladder absorption and perfusate and tissue prostaglandin E and 6 keto prostaglandin F1 alpha concentrations were evaluated. To determine whether capsaicin induced gallbladder inflammation, tissue myeloperoxidase concentrations were measured. Control feline gallbladders absorbed approximately 0.6 ml/hr. Indomethacin alone significantly decreased gallbladder absorption. Capsaicin administration increased gallbladder absorption to approximately 1.6 ml/hr, and this increase was significantly inhibited by indomethacin. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916669 TI - Adaptive regulation of hepatic bile salt transport: effects of alloxan diabetes in the rat. AB - The hepatic transport of bile salts appears to be adaptively regulated by changes in the bile salt pool size and in the flux of bile salt through the liver. The maximum secretory rate of taurocholate increases or decreases when the bile salt pool size is modified by either oral feeding of cholate or taurocholate (up regulation) or prolonged bile salt depletion through a biliary fistula (down regulation), respectively. It is not known whether adaptive regulation of hepatic bile salt transport operates under conditions in which the bile salt pool size is modified by endogenous changes in bile acid metabolism. Because experimental diabetes mellitus is associated with alterations in the synthesis of bile acids and total bile salt pool size and composition in the rat, we examined the effects of diabetes mellitus induced by alloxan (5 mg/100 gm body weight, intravenously) and insulin treatment on hepatic bile salt transport and relate the changes to bile salt pool size variations. At 3 days after alloxan injection (DIAB-3 group) both taurocholate maximum secretory rate and pool size were significantly decreased, whereas they were restored to normal values after 6 days of diabetes (DIAB-6 group). Insulinopenic diabetes for 14 days (DIAB-14 group) and for 24 days (DIAB-24 group) resulted in a marked increase of basal bile salt secretory rate (secondary to an increased contribution of cholate conjugates) and an enhanced taurocholate maximum secretory rate compared with control rats (147% and 188% increase, respectively) and with a group (PHARM-control) that received alloxan but did not develop detectable glycosuria (224% and 286% increase, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916670 TI - Dietary fish oil effects on biliary lipid secretion and cholesterol gallstone formation in the African green monkey. AB - We studied two groups of adult male African green monkeys to assess the effects of dietary fish oil on biliary lipid secretion and cholesterol gallstone formation. One group was fed 0.8 mg cholesterol/kcal and 42% of calories as fat with half of the fat calories derived from lard; the other group was fed a similar diet except for the isocaloric substitution of menhaden oil for lard. After 2 1/2 to 3 yr, necropsies were performed and the presence of gallstones was determined. Gallbladder bile specimens were analyzed for cholesterol saturation index, as well as for bile acid species and biliary phospholipid fatty acid composition. Our results showed that 67% of animals fed the lard diet had cholesterol gallstones compared with only 22% of animals in the group fed the fish oil diet (p = 0.08). The cholesterol saturation index of gallbladder bile also tended to be higher in the lard-fed group (1.15 +/- 0.11) compared with the fish oil-fed group (0.86 +/- 0.09, p = 0.06). No differences between the two dietary groups were noted in the percentages of the various types of bile acids. However, a greater percentage of omega-3 fatty acids and a lesser percentage of 18:1, 18:2 and 20:4 fatty acids were found in the biliary phospholipids from the fish oil-fed group compared with the lard-fed group. Biliary lipid secretion rates were then measured during isolated recirculating liver perfusion performed with a constant sodium taurocholate infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916671 TI - The effect of GABA on serum and hepatic polyamine concentrations after partial hepatectomy in rats. AB - Serum and hepatic polyamine concentrations including putrescine, spermidine and spermine were documented at various time intervals after partial hepatectomy in rats treated with GABA (500 micrograms/gm body wt) or isotonic saline. Aside from a transient decrease in spermidine levels, GABA treatment had no effect on serum polyamine concentrations. In the liver, however, GABA treatment markedly attenuated the increase in hepatic putrescine concentrations that occurs after partial hepatectomy such that levels were 64%, 74% and 100% lower than in saline treated controls on days 1, 2 and 3 after partial hepatectomy (p less than 0.005, p less than 0.01 and p less than 0.05, respectively). Spermidine and spermine concentrations in the liver were not affected by GABA treatment. To determine the mechanism whereby GABA lowers putrescine concentrations in regenerating liver, ornithine decarboxylase messenger RNA and enzyme activity were documented after GABA treatment. Although ornithine decarboxylase messenger RNA levels were similar, ornithine decarboxylase enzyme activity was significantly inhibited 12 hr after partial hepatectomy in GABA-treated rats compared with saline-treated controls. The results of this study indicate that GABA inhibits hepatic putrescine synthesis at a posttranscriptional level in rats after partial hepatectomy. These results could help to explain the impairment in hepatic regenerative activity that occurs in patients with elevated serum GABA concentrations and fulminant hepatic failure. PMID- 1916668 TI - Screening for candidate hepatic growth factors by selective portal infusion after canine Eck's fistula. AB - Completely diverting portacaval shunt (Eck's fistula) in dogs causes hepatocyte atrophy, disruption of hepatocyte organelles, fatty infiltration and low-grade hyperplasia. The effect of hepatic growth regulatory substances on these changes was assessed by constantly infusing test substances for four postoperative days after Eck's fistula into the detached left protal vein above the shunt. The directly infused left lobes were compared histopathologically with the untreated right lobes. In what has been called an hepatotrophic effect, stimulatory substances prevented the atrophy and increased hepatocyte mitoses. Of the hormones tested, only insulin was strongly hepatotrophic; T3 had a minor effect, and glucagon, prolactin, angiotensin II, vasopressin, norepinephrine and estradiol were inert. Insulin-like growth factor, hepatic stimulatory substance, transforming growth factor-alpha and hepatocyte growth factor (also known as hematopoietin A) were powerfully hepatotrophic, but epidermal growth factor had a barely discernible effect. Transforming growth factor-beta was inhibitory, but tamoxifen, interleukin-1 and interleukin-2 had no effect. The hepatotrophic action of insulin was not altered when the insulin infusate was mixed with transforming growth factor-beta or tamoxifen. These experiments show the importance of in vivo in addition to in vitro testing of putative growth control factors. They illustrate how Eck's fistula model can be used to screen for such substances and possibly to help delineate their mechanisms of action. PMID- 1916672 TI - Urinary excretion of lithocholic acid and its conjugates by the bile duct-ligated rat. AB - The 3-O-glucuronide of lithocholic acid has been shown to be a potent cholestatic agent in rats. However, even after the onset of lithocholic acid glucuronide induced cholestasis, little of the administered material was recovered in urine. To determine whether this phenomenon was related to the steroid moiety or the form of conjugation, small doses of radiolabeled lithocholic acid glucuronide, lithocholic acid, taurolithocholic acid and/or lithocholic acid sulfate were administered to rats with ligated bile ducts. Urinary excretion of isotope was followed for 24 hr and urinary metabolites of the administered compounds were identified by thin-layer chromatography. Lithocholic and taurolithocholic acids were slowly but relatively efficiently excreted in urine with 73% and 91% of the dose, respectively, recovered in urine over 24 hr. More than 80% of the label in urine from animals receiving these two compounds was in the form of taurine conjugated beta-muricholic acid. In contrast, lithocholic acid 3-glucuronide and 3-sulfate were poorly excreted: 9% and 12% of the administered doses, respectively, were recovered in urine in 24 hr. Of the small amount of label in urine from rats given the glucuronide, 90% was identified as lithocholic and taurolithocholic acid glucuronides. When lithocholic acid sulfate was given, thin layer chromatography of urine showed two peaks, which were tentatively identified as tauromurideoxycholic and taurolithocholic acid sulfates. More definitive identification was not possible because of the small amount of the administered dose excreted in urine in these forms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916673 TI - Effects of single ethanol administration on hepatic ornithine decarboxylase induction and polyamine metabolism. AB - The effects of a single ethanol administration on ornithine decarboxylase induction, polyamine metabolism and DNA synthesis in rat liver after partial hepatectomy were studied. Ethanol given 1 hr before partial hepatectomy at the dose of 2, 3 or 5 gm/kg body wt inhibited the increase in ornithine decarboxylase activity and that in the putrescine level in the liver 4 hr after partial hepatectomy. The hepatectomy increased the amount of ornithine decarboxylase messenger RNA expressed, and this amount was unaffected by ethanol administration. Further, ethanol did not accelerate the degradation of ornithine decarboxylase 4 hr after partial hepatectomy, indicating that the inhibition of ornithine decarboxylase activity caused by ethanol was not caused by a decrease in the ornithine decarboxylase messenger RNA level or by the acceleration of ODC degradation. The single dose of ethanol inhibited [3H]thymidine incorporation into the hepatic DNA 24 hr after partial hepatectomy. The suppression of [3H]thymidine incorporation was partially reversed by the administration of putrescine. These results suggested that ethanol inhibits the increase in ornithine decarboxylase activity after transcription, suppressing the accumulation of putrescine, which prevents DNA synthesis in response to hepatectomy. PMID- 1916675 TI - Intracranial pressure waves and intracranial hypertension in rats with ischemic fulminant hepatic failure. AB - Brain edema and intracranial hypertension are a major cause of death in fulminant hepatic failure. We have shown that brain water measured in rats after hepatic devascularization (portacaval anastomosis followed in 24 to 48 hr by ligation of the hepatic artery) increases with the progression of encephalopathy. In this study, we examined whether intracranial hypertension develops in this model of fulminant hepatic failure. Using a fiberoptic pressure transducer, intracranial pressure rose from 3.3 +/- 1.1 mm Hg to 23.7 +/- 2.7 mm Hg (mean +/- S.E.M.) by the time the corneal reflex was lost; intracranial pressure was unchanged in control rats. Immediately after ligation of the hepatic artery, intracranial pressure was normal and remained stable until the last hours of the experiment, when it progressively rose, suggesting a loss of intracranial compliance. In addition, sudden and short episodes of marked increases in intracranial pressure (greater than 50 mm Hg) not related to seizure activity markedly decreased cerebral perfusion pressure. Internal carotid artery blood flow, an indirect measure of cerebral perfusion, decreased 29% +/- 12% by the end of the experiment. The time elapsed from ligation of the hepatic artery until loss of the corneal reflex (range 340 to 940 min) was related to the change in cerebral perfusion pressure, suggesting that an increase in systemic arterial pressure at the time of the initial rise in intracranial pressure may result in an increased length of survival. In this animal model, widely used to study the pathogenesis of hepatic encephalopathy, intracranial hypertension invariably appears in the terminal phase of the course. The development of intracranial pressure waves may be an indication that brain herniation is imminent. PMID- 1916674 TI - Canine bile contains anticrystallization factors that inhibit precipitation of calcium carbonate. AB - Previous studies have strongly suggested that human bile contains a substance(s) that interferes with the precipitation of calcium phosphate and carbonate from solution. These studies, however, did not distinguish between calcium binding by biliary constituents resulting in decreased calcium carbonate saturation (alterations in solution thermodynamics) and true inhibition of calcium salt precipitation by kinetic factors. Because our recent studies have shown that canine common duct bile is always supersaturated with calcium carbonate (thermodynamically at risk for precipitation), we hypothesized that it must contain kinetic factors that inhibit formation and/or growth of calcium carbonate crystals. Effects of canine bile, bovine albumin and the bile salt taurocholate on calcium carbonate precipitation were studied in highly supersaturated solutions of calcium carbonate that spontaneously undergo rapid precipitation. Measured free ionized calcium concentrations, [Ca++], and calculated calcium carbonate saturation indices were compared in test solutions and controls to evaluate the thermodynamic effects of test solutions on the degree of saturation in the assay system. It is shown that addition of only 0.2 ml of normal canine gallbladder bile to the assay system (a 1:101 dilution of biliary components) abolished precipitation. A lesser inhibitory effect (a decrease in the rate of precipitation) was observed when gallbladder bile was diluted but was lost after 10-fold dilution. Canine common duct bile caused a decrease in the rate of precipitation similar to diluted gallbladder bile. In contrast, sodium taurocholate (250 mmol/L), the major bile salt in the dog, and albumin (1.5 gm/L), the most abundant protein in bile, had only a minimal inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916676 TI - Current concepts in cell-mediated hepatic allograft rejection leading to ductopenia and liver failure. AB - Hepatic allograft rejection is presently classified into acute and chronic rejection based on histological features, timing and reversibility. However, because features of both types of rejection can occur at any time, and in many combinations, the terms "acute" and "chronic" seem inappropriate in some instances. Thus the term "cellular rejection" better defines the histological features of portal hepatitis, nonsuppurative destructive cholangitis and endotheliitis, which are independent of time and response to therapy. Similarly, because progressive bile duct destruction leading to a decrease in the number of interlobular and septal bile ducts is the major histological feature of "chronic rejection," the term "ductopenic rejection," defined as the loss of bile ducts in 50% or more of portal tracts independent of time and reversibility, seems more appropriate. The pathogenesis of cell-mediated rejection has not been completely explained; however, direct immunocytic attack on small bile ducts and small arteries appear to be the major feature. The process may lead to bile duct loss ("ductopenia"). The pathogenetic role of foam-cell arteritis resulting in ischemic bile duct injury and the role of humoral mechanisms in causing ductopenic rejection awaits further clarification. In the past, irreversible ductopenic rejection occurred in approximately 10% of all patients who underwent their first liver transplantation; this figure, however, appears to be decreasing. The clinical features of irreversible rejection include persistent and progressive cholestasis; rising serum levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase; and a decrease in hepatic synthetic function. Ductopenic rejection can occur early (2 to 5 wk after liver transplantation) but most often develops between 6 wk and 6 mo after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916677 TI - A hepatorenal depressor reflex: a possible clue to the pathogenesis of the hepatorenal syndrome. PMID- 1916678 TI - Hepatitis C: improving the diagnostic armamentarium. PMID- 1916679 TI - Hepatocyte growth factor receptor and the c-met oncogene. PMID- 1916680 TI - Transforming growth factor B and hepatic fibrosis: cause or effect? PMID- 1916681 TI - The American Association for the Study of Liver Diseases. Postgraduate course & 42nd annual meeting. November 2-5, 1991, Chicago, Illinois. Abstracts. PMID- 1916682 TI - Gastrointestinal manifestations of type 1 neurofibromatosis (von Recklinghausen's disease). AB - Gastrointestinal involvement in von Recklinghausen's disease occurs in three principal forms: hyperplasia of the submucosal and myenteric nerve plexuses and mucosal ganglioneuromatosis which leads to disordered gut motility; gastrointestinal stromal tumours showing varying degrees of neural or smooth muscle differentiation; and a distinctive glandular, somatostatin-rich carcinoid of the periampullary region of the duodenum that contains psammoma bodies and which may be associated with phaeochromocytoma. This review describes the histopathological features of these lesions and discusses potential pitfalls in their differential diagnosis. Their accurate identification has significant implications for clinical management and may even provide the first pointer to the diagnosis of neurofibromatosis. PMID- 1916683 TI - Thin malignant melanomas. PMID- 1916684 TI - A histopathological study of the appendix at autopsy and after surgical resection. PMID- 1916685 TI - Sclerosing lymphocytic lobulitis of the breast--evidence for an autoimmune pathogenesis. AB - We describe 13 cases of inflammatory lesion of breast lobules in young and middle aged women, presenting as breast lumps, with, in five cases, associated breast pain. The patient with the most florid bilateral disease subsequently developed Hashimoto's thyroiditis. This prompted us to consider an autoimmune pathogenesis for all the breast lesions. We confirm a previously documented association of such breast lesions with diabetes mellitus and review the evidence for a possible HLA association. Increased HLA-DR expression by breast epithelial cells was observed in cases available for study. Of the seven patients screened for circulating autoantibodies, three had none, one had smooth muscle antibodies, one parietal cell, one parietal cell and thyroid microsomal, and the seventh had the thyroid autoantibodies expected in Hashimoto's disease. Five of seven patients whose HLA-status was determined were HLA-DR3, 4 or 5 positive, either singly or in combination. Immunophenotypic analysis of the mammary lymphoid infiltrate showed that the majority of infiltrating lymphocytes were B-cells. PMID- 1916686 TI - Epithelial damage by Helicobacter pylori in gastric ulcers. AB - On review of 136 consecutive biopsies of benign gastric ulcer, Helicobacter pylori was detected in 78 cases (57.3%). The gastric epithelium colonized by Helicobacter pylori showed a characteristic constellation of changes, including loss of apical mucous portion of individual cells, drop-out of epithelial cells, epithelial pits, erosions and cellular tufts, indicative of cellular injury and regeneration. Among the 58 Helicobacter-negative cases, similar changes were not observed in the ulcer edges, except for two cases which exhibited some cellular tufts. Thus, the topographic association of Helicobacter pylori with epithelial damage in the gastric ulcer edges in more than half of the cases suggests that this organism probably plays an aetiological role in ulcerogenesis, at least in these cases. Furthermore, the epithelial changes are so distinctive that they can serve as a helpful histological indicator for the presence of Helicobacter pylori in gastric biopsies. PMID- 1916687 TI - Lymphoid follicular hyperplasia--a distinctive feature of diversion colitis. AB - Diversion colitis refers to the inflammatory changes that occur in the defunctioned segment of the large intestine following diversion of the faecal stream. We report the histological features in the defunctioned rectums from seven patients: one each with severe constipation and Behcet's disease, two with Crohn's disease with rectal sparing and three with ulcerative colitis. The appearances of diversion colitis in a previously normal rectum are compared with diversion colitis with superimposed inflammatory bowel disease. Lymphoid follicular hyperplasia was found in all cases. This was marked in patients with inflammatory bowel disease, with or without initial rectal involvement. Other changes comprised surface epithelial degeneration and ulceration, mucosal inflammation including crypt abscesses, and crypt branching. Inflammatory and crypt changes were mild, except in ulcerative colitis where changes were marked and resembled those of the proximal colon. Lymphoid hyperplasia is a distinctive feature in diversion colitis. The term follicular proctitis, previously used to indicate chronic ulcerative colitis exclusively, should be re-examined. PMID- 1916688 TI - Lymphocyte predominance Hodgkin's disease (nodular paragranuloma)--a bcl-2 negative germinal centre lymphoma. AB - Hodgkin's disease, lymphocyte predominance type (nodular paragranuloma), is of germinal centre origin and the tumour cells have a B-cell phenotype. As the T(14;18) translocation, and the subsequent expression of bcl-2 protein by germinal centre cells, is the most characteristic finding of centroblastic centrocytic lymphoma, we have tested a series of 11 cases of lymphocyte predominance Hodgkin's disease, using Southern blot analysis for the major breakpoint region and the minor breakpoint cluster region, polymerase chain reaction with primers for the major and minor breakpoint cluster region, and immunohistological studies with a monoclonal antibody specific for the bcl-2 protein. All three techniques gave negative results in the cases of Hodgkin's disease, establishing a clear differentiation from centroblastic-centrocytic lymphoma. These findings are useful in the differential diagnosis between the two entities and raise the question of the non-clonal nature of lymphocyte predominance Hodgkin's disease. PMID- 1916689 TI - Autoimmune oophoritis associated with polycystic ovaries. AB - Autoimmune oophoritis is a rare cause of premature ovarian failure. Previous histological descriptions are sparse, with even fewer reports of cystic ovaries associated with this condition. Two cases of autoimmune oophoritis presenting as cystic ovaries with menstrual abnormalities are described, with immunocytochemical analysis of the inflammatory cell infiltrate. Serum autoantibodies to ovary and adrenal were present in both cases. Although rare, recognition of the condition by histopathologists is important because of the strong association with other 'organ-specific' autoimmune diseases, especially idiopathic Addison's disease. A review of the 17 reported cases indicates five where cystic changes were present in the ovary. PMID- 1916690 TI - Intracytoplasmic lumina--a useful diagnostic feature of adenocarcinomas. AB - The monoclonal antibody NCRC-11, which has epithelial membrane antigen (EMA)-like immunoreactivity, was used to identify intracytoplasmic lumina in a series of 105 adenocarcinomas from various sites and in 283 breast carcinomas; 55% of the non breast carcinomas and all breast carcinomas except one of spindle cell type contained intracytoplasmic lumina. The highest frequency (16.4% of tumour cells) was found in invasive lobular carcinoma of the breast. The use of antibodies with EMA reactivity is advocated in the routine investigation of metastatic and undifferentiated tumours. PMID- 1916691 TI - Intra-abdominal pacinian neuroma: a rare lesion in an unusual location. PMID- 1916692 TI - Fibrin-ring granulomas: a non-specific reaction to liver injury? PMID- 1916694 TI - Cutaneous ciliated cyst. PMID- 1916693 TI - Gastric localization of systemic leishmaniasis in a patient with AIDS. PMID- 1916695 TI - Hodgkin's disease and sinus histiocytosis with massive lymphadenopathy-like changes. AB - Sinus histiocytosis with massive lymphadenopathy (SHML) is a disorder of unknown origin which is only infrequently associated with lymphoid neoplasms. We report the first two cases of Hodgkin's disease with simultaneous SHML-like changes in the same lymph node. PMID- 1916696 TI - High-grade T-cell lymphoma following treatment with cyclosporin A. AB - A 47-year-old man with persistent severe oropharyngeal ulceration developed a high-grade T-cell lymphoma soon after commencing treatment with cyclosporin A. Using Southern blotting to identify T-cell beta-chain gene rearrangements, evidence of clonal restriction was found both in blood and lymph node DNA samples. Two BamH1 rearranged bands were demonstrated in both samples. In the blood a 16 Kb band predominated, with a weaker 28 kb band. In the lymph node sample this pattern was reversed. The findings suggest that a bi-clonal population of T-lymphocytes or clonal evolution of an existing T-cell monoclone had developed, and that cyclosporin contributed to the emergence of a high-grade T-cell lymphoma. PMID- 1916697 TI - Immunolocalization of urokinase-type plasminogen activator in adenomas and carcinomas of the colorectum. AB - Carcinogenesis in the human colon is associated with a marked increase in the tissue content of the urokinase-type plasminogen activator (u-PA). This study was performed to determine the type of cells responsible for the u-PA increase in carcinomas of the colon and in their precursor lesions, the adenomas, by immunohistological evaluation applying monoclonal antibody 3689 directed to the beta-chain of u-PA. Normal intestinal mucosa (n = 17) showed hardly any staining of u-PA, but some lamina propria cells were faintly positive. Carcinomas (n = 17) and adenomas (n = 16) showed a considerable and comparable staining intensity of u-PA in neoplastic columnar epithelial cells, and this staining was found to be diffuse and cytoplasmic. In a majority of the neoplastic tissues the u-PA staining was found to be patchy and not related to known risk markers of malignancy such as dysplasia in the adenomas, or to prognostic determinants such as Dukes' classification or differentiation in the carcinomas. The observation of strong u-PA positive lamina propria cells in adenomas but infrequently observed in normal mucosa and carcinomas was noteworthy. u-PA staining intensity of the tissue sections was found to correlate well with the u-PA antigen level in the tissue extracts determined by ELISA (r = 0.52, P = 0.0001) but poorly with the u PA activity determined enzymatically (r = 0.28, P = 0.05). In conclusion, the u PA increase in neoplasia of the human colon can be attributed to an increased diffuse cytoplasmic content of u-PA in neoplastic columnar epithelial cells. PMID- 1916699 TI - Mac387: its non-specificity as a tumour marker or marker of histiocytes. AB - A commercially available monoclonal antibody which detects histiocytes in paraffin sections, Mac387, was reacted with 148 soft tissue sarcomas, 29 carcinomas and 10 malignant melanomas. The soft tissue sarcomas had been previously immunophenotyped. All categories of sarcomas, with the exception of angiosarcomas, were positive. Most showed staining in less than 50% of the tumour cells. Six of 10 adenocarcinomas and three of nine basal cell carcinomas were positive, while squamous carcinomas and malignant melanomas were negative. Normal squamous mucosa and epidermis were also positive. The results of this study suggest that Mac387 is of little value in the differential diagnosis of soft tissue tumours, nor is it a specific histiocytic marker. PMID- 1916698 TI - A new insight into the histogenesis of 'mesodermomas'--malignant mesotheliomas. AB - A myogenic phenotype was induced in cultures of human mesothelial cells treated for 72 h with atrazine, a triazine derivative. Immunoreactivity for both myosin and myoglobin was detected in a large number of these cells, irrespective of their polygonal or spindle morphology, whereas no expression of desmin was observed. These findings support the embryological identity of mesothelium and mesoderm, the former being, in the post-embryonic stage, potentially capable of differentiation along the same lineages which the latter normally displays during embryogenesis. In the light of this concept it can be assumed that primary malignancies arising from the mesothelium have the competence to express the pluripotent nature of embryonic mesoderm, and hence the term mesodermoma is appropriate for this group of tumours, including mesotheliomas in a classical sense. A postulated mechanism for the phenotypic change of mesothelial cells is also outlined, involving atrazine conversion to 5-aza-chloro-cytidine, a probable DNA hypomethylating and gene activating agent, like its analogue 5-azacytidine. PMID- 1916700 TI - Primary leiomyosarcoma of bone. AB - Four cases of primary leiomyosarcoma of bone are presented. The histology of this rare tumour has been studied with a panel of monoclonal antibodies to the intermediate filaments desmin and vimentin, and to other markers including smooth muscle actin, myosin, alpha 1-antitrypsin, alpha 1-antichymotrypsin, lysozyme, S 100 protein and cytokeratin. The tumour cells were uniformly positive for desmin, vimentin, and in one case for smooth muscle actin; all the other markers were negative. The findings have been compared with other spindle cell lesions of bone and with electron-microscopy of the tumours. Immunohistochemistry allows the histological diagnosis to be made without the need to resort to ultrastructural studies. PMID- 1916701 TI - The changing phenotypic appearance of a malignant vulval neoplasm containing both carcinomatous and sarcomatous elements. AB - We describe the changing phenotypic appearance over a 7-year period of a malignant neoplasm of the vulva. This lesion was studied by light and electronmicroscopy and immunohistochemical techniques. The tumour contained both carcinomatous and sarcomatous elements including osteosarcomatous differentiation. To our knowledge osteosarcomatous differentiation has not been reported previously at this site. We submit that the best term for this type of neoplasm, based on tumour differentiation rather than reputed histogenesis, is carcinosarcoma. Tumours such as these occurring in the female genital tract should be distinguished from metastatic mixed Mullerian tumours. PMID- 1916702 TI - Testicular regression syndrome--a pathological study of 77 cases. AB - Testicular regression syndrome is characterized by a rudimentary epididymis and spermatic cord with absence of testicular tissue. Although it has been well described in the surgical literature, few pathological studies have been performed. We report 77 cases of the syndrome, deriving from a 26-year retrospective review. Typical gross descriptions described several cm of spermatic cord with a small mass of firm, fibrotic tissue at one end; elements of the vas deferens, spermatic artery and venous plexuses were usually present. Histologically, the distal expansion of most of the specimens was composed of dense fibrovascular tissue with no evidence of seminiferous tubules or normal testicular elements. Instead, scattered foci of calcification and brown pigment were present. The finding of dystrophic calcification and haemosiderin deposition, with no evidence of viable testicular tissue, in the presence of relatively normal spermatic cord elements, supports the concept of generally unilateral and occasionally bilateral anorchia secondary to remote infarction. The young age of the patients, coupled with the history of an absent testis from birth, is supportive of in utero damage. These histopathological findings provide support for the concept of in utero torsion of the testis as the basis for the testicular regression syndrome. PMID- 1916703 TI - Malakoplakia of the middle ear. PMID- 1916704 TI - Palisading granuloma of the ovary. PMID- 1916705 TI - Pseudo-epitheliomatous hyperplasia in thymic cysts. PMID- 1916706 TI - Hashimoto's disease in a benign cystic teratoma of the ovary. PMID- 1916707 TI - Duodenal adenocarcinoma complicating coeliac disease. PMID- 1916708 TI - More women using new birth-site options. PMID- 1916709 TI - Information overload: CEOs seek new tools for effective decision making. AB - The amount of data available to hospital CEOs is growing exponentially. But these numbers are worthless if executives can't use them to make effective decisions. As one CFO puts it, "Information systems are only helpful so long as you have the management processes that allow you to use the data." PMID- 1916710 TI - Survey: CEOs rate usefulness of data-based reports. PMID- 1916711 TI - Sizing up systems: researchers to test performance measures. AB - Researchers are preparing to test 81 possible performance indicators that health care systems can use to more thoroughly measure how well they are carrying out their missions. In addition to measurements of financial performance and quality, the indicators cover such areas as community service and customer satisfaction. PMID- 1916712 TI - Hospitals probe job candidates' values for organizational 'fit'. AB - In trying to fulfill their institutional missions, hospitals are seeking out ways to identify job candidates who share their organizational values. To that end, they are increasingly incorporating psychological testing and structured interviewing into the selection and promotion process. PMID- 1916713 TI - Hospitals wary of interpretation of medical device reporting law. PMID- 1916714 TI - Hospitals go back to basics to attract referring physicians. PMID- 1916715 TI - Policies to limit life-sustaining treatment. PMID- 1916716 TI - Will new technology solve integration problems? PMID- 1916717 TI - Former Surgeon General Koop speaks out on health care reform and policy issues. Interview by Mark Hagland. PMID- 1916718 TI - Hospitals get chance to equip offices for less. PMID- 1916719 TI - States battle new Medicaid funding regulations. PMID- 1916721 TI - CEOs expect slow, steady managed care growth. PMID- 1916720 TI - Tough times force CEOs to adjust career paths. PMID- 1916722 TI - Currents ... payment. PMID- 1916723 TI - Technology acquisition: trends in imaging. AB - A great deal has happened in the imaging area this year. Our imaging special report examines changes in the field: from hospitals' new negotiating tactics to the impact of the new Medicare capital payment regulation. In an in-depth report, we examine new trends developing in hospitals' and hospital groups' contracting for imaging equipment purchasing. Then we take a look at how hospitals' technology acquisition strategies--and vendors' research and development plans- are being remolded by the new capital regulation. Finally, we revisit the capital fold-in regulation itself. PMID- 1916724 TI - CEOs: well-informed reporters can be powerful hospital allies. AB - Working with the news media to achieve accurate, fair reporting on one's hospital can be a time-consuming chore, but CEOs say the effort is well worth it. Sometimes, even crisis-mode media management can have its upside. PMID- 1916725 TI - Expenses dip to 5-year low; interest rates ease, inflation slows, but admissions fall. PMID- 1916726 TI - PROs' new quality improvement focus: will it work in practice? AB - According to the Health Care Financing Administration, the PRO program's new emphasis on outcomes addresses provider concerns about subjectivity in the review process. But providers are wary of how it will play out. PMID- 1916727 TI - Nurses seek expanded role in clinical quality improvement. PMID- 1916728 TI - The best approach to recruiting women MDs. PMID- 1916729 TI - Long-term career planning: flexibility is key. PMID- 1916730 TI - Weakest hospitals getting weaker, new HFMA data show. PMID- 1916731 TI - Nursing homes change image to attract workers. PMID- 1916732 TI - Feds: provider capacity critical to Oregon's success. PMID- 1916733 TI - EPO helps hospital save millions on employee benefits. PMID- 1916734 TI - Mental health care: the challenge for hospitals. PMID- 1916735 TI - Polymorphisms at VNTR loci suggest homogeneity of the white population of Utah. AB - Apparent departure from equilibrium of genetic parameters measured for multiallelic single-locus markers such as VNTR (variable number of tandem repeat) loci has been suggested as evidence of underlying heterogeneity of the tested population. Using allele frequency distributions at eight VNTR loci from the white population of Utah, we show that the observed number of alleles and the gene diversity at each locus are congruent according to expectations of the neutral mutation model. This demonstrates the genetic homogeneity of the white population of Utah with reference to the allele (total and rare) frequency distribution at eight VNTR loci. The importance of such procedures is discussed in the context of using VNTR polymorphism data for forensic and medicolegal applications. Recommendations for reporting population data for hypervariable loci are also made to aid potential users in conducting similar analyses. PMID- 1916736 TI - Ancient movement patterns determine modern genetic variances in Europe. AB - A summary ethnohistory database on population movements in Europe between 2000 B.C. and A.D. 1970 was related to genetic variances and distances based on 26 genetic systems. For the purposes of these analyses, Europe was divided into 85 terrestrial quadrats measuring 5 degrees x 5 degrees. Counts, stratified by time, were taken of the number of movements out of and into each quadrat (called source and target counts, respectively) and between each pair of quadrats. The source and target counts have distinct and different patterns in Europe and vary significantly over time. Central Europe and the Pontic area have the quadrats with the highest source counts, and the Balkans have the highest target counts. Modern genetic variances per quadrat are significantly correlated with source and target counts, somewhat more prominently with source counts. Genetic distances between pairs of quadrats are correlated strongly with geographic distances and moderately and negatively correlated with the total number of movements between these quadrats. Partial correlations of genetic distances with total number of movements, holding geographic distance constant, are small and mostly nonsignificant. These results are interpreted in light of our knowledge of the history and biology of the populations concerned. PMID- 1916737 TI - Genetic and cultural transmission in Sicily as revealed by names and surnames. AB - The study of names as cultural characters and of surnames, which behave like genetic markers, is useful for comparing cultural and genetic transmission. Genetic transmission has a unique vertical component, which also can be present in the transmission of cultural traits associated with a horizontal (or epidemic) component resulting from local customs or fashion. Our aims in this study are to infer genetic patterns in Sicily from surnames and names and to evaluate and compare the consequences of vertical versus horizontal transmission of cultural markers. Names and surnames of 88,383 consanguineous spouses collected in 16 dioceses of Sicily were analyzed by multivariate analysis to reveal and compare the geographic clusters obtained from both sets of data. As a result, both data sets indicate a major separation between the eastern and the western region of Sicily. Also, distance matrices obtained from names are highly correlated with those from surnames. But names seem to form fewer and larger geographic clusters, whereas surnames are more greatly subdivided into smaller clusters. The most common male names present a different pattern from surnames. Vertical transmission is the cause of the similarity of the main geographic patterns of names and surnames and their correspondence with findings from geography of genes, and horizontal cultural transmission explains the major differences. Furthermore, the genetic and cultural affinities can be correlated with the historical background of Sicily. PMID- 1916738 TI - Effect of changes in population size on genetic microdifferentiation. AB - Changes in local population size are expected to have an effect on the degree of genetic microdifferentiation. A decrease in population size is expected to lead to an increase in microdifferentiation, and an increase in population size to a decrease in microdifferentiation. These expectations are routinely used with historical and/or demographic data to evaluate changes in estimates of microdifferentiation obtained over time for human populations. Here I look more closely at these expectations by using simple mathematical models that relate a change in average effective population size to the degree of microdifferentiation. The direction of change in microdifferentiation is influenced by the migration structure of the populations and the proximity of the region to an equilibrium state. A change in population size always leads to a new equilibrium, but the speed at which this new equilibrium is reached depends on migration and time depth. A decline in population size in one generation always leads to an immediate increase in the degree of microdifferentiation. An increase in population size in one generation could lead to an initial decrease or increase in the degree of microdifferentiation or to no change at all. Consideration of the parameters of the models shows under what conditions such changes occur. The relevance of these models is explored using summary data from a number of human populations. PMID- 1916740 TI - Doubts about isonymy. AB - The method of isonymy, developed by Crow and Mange for estimating inbreeding from surname frequencies, requires an assumption that has not been appreciated: It is necessary to assume that all males in some ancestral generation, the founding stock, had unique surnames. Because this assumption is seldom justified in real populations, the applicability of the isonymy method is extremely limited. Even worse, the estimates it provides refer to an unspecified founding stock, and this implies that these estimates are devoid of information. PMID- 1916739 TI - Geographic distributions of within-population variability in blood pressure. AB - Data on mean blood pressure with standard deviation were extracted from the medical and anthropologic literature for as many populations as possible. The populations were classified as traditional, transitional, or modern. Both mean and within-population variability were found to be higher in more modern populations, confirming the prediction that variability of a character of low heritability is higher in an adverse environment, where it is more difficult to maintain homeostasis. In addition, variability increases with age, indicating a breakdown in homeostasis with aging. On average, males had higher diastolic blood pressure than females, and on average, females had greater variability in systolic blood pressure than males. There was a highly significant negative relationship between latitude and within-population variability in blood pressure. PMID- 1916741 TI - Severe combined immunodeficiency among the Navajo. I. Characterization of phenotypes, epidemiology, and population genetics. AB - Previous studies have identified a high incidence of severe combined immunodeficiency (SCID) among the Navajo Native American population. To determine the incidence and population genetics of this condition, we reviewed the death certificates of all children who died between 1969 and 1982, established the cases that met criteria identified in previously investigated cases, and interviewed the selected children's families. SCID cases were distributed spatially and temporally. Segregation parameter estimates of 0.27-0.38 were obtained from data from 24 interviewed families, suggesting an estimated gene frequency of 2.1% (arguing against a multifactorial inheritance). SCID cases referred to specialty centers lacked T and B cells in their blood, and their serum immunoglobulins ranged from absent to near normal. PMID- 1916742 TI - Modeling the AIDS epidemic in Mexico City. AB - To study the future course of the AIDS epidemic in Mexico City, we use an open compartmental model to forecast new AIDS cases among homosexual and bisexual males and among heterosexual males and females. For each group three compartments are defined: uninfected persons, infected but asymptomatic persons, and persons diagnosed with AIDS. It is assumed that the AIDS epidemic will follow the propagation of infectious disease model, where spread of infection is proportional to the product of the number of healthy persons and the number of infected ones. The compartmental model is represented by a system of nonlinear differential equations describing the rate of change in the number of persons in each compartment. The impact of preventive measures is explored by decreasing the probability of HIV transmission, which is one of the model parameters representing behavioral patterns. By April 1989, 491 AIDS cases had been reported in Mexico City and classified as sexually related. Our model predicts that the AIDS incidence will continue to rise in Mexico City for the foreseeable future and will spread among the heterosexual population. Decreasing the transmission probability by 10% in all groups (through education programs) will result in a decrease of 18.1% in the number of accumulated cases over a 5-year period. A 20% decrease would prevent more than 31% of the cases. We conclude that mathematical models can be valuable in predicting the spread of the AIDS epidemic and the impact of behavioral change on its spread. PMID- 1916744 TI - Seasonality of triplet births in the United States. AB - Birth data on 1050 sets of triplets delivered in the United States from 1985 to 1988 were analyzed to establish whether seasonal variations in the number of triplet births occur. These data were compared to live birth data from the entire United States population over a similar period; the US data exhibit a seasonal variation with a peak in late summer. Seasonality in the number of triplet births was noted, and it differed significantly (p = 0.01) from that of the entire US population. A large peak in triplet births was seen in the spring (April-May) and a smaller peak in late summer (August-September). Only minor differences in these trends could be observed when triplet data were stratified by cause of pregnancy (spontaneous versus drug-induced ovulation) or corrected for the shorter gestations of triplet pregnancies. PMID- 1916743 TI - Demographic study of one sedentary and two migrant populations of eastern India. AB - Demographic data were collected from 185 sedentary Oraon of Gumla district of Bihar, 255 migrant Oraon, and 242 migrant Tamang households, covering a total population of 1009, 1414, and 1537 individuals, respectively. Both migrant groups were tea garden laborers working in the Birpara, Lankapara, and Tulsipara tea gardens in the Jalpaiguri district, West Bengal, India. The present study reveals that the migrant Oraon possess significantly higher fertility and (infant) mortality than the sedentary Oraons even though they are a genetically similar group. The study also reveals that the two migrant groups differ with respect to both fertility and mortality even though they inhabit similar physical and sociocultural environments. PMID- 1916745 TI - Note on estimates of the inbreeding coefficient through study of pedigrees and isonymous marriages. AB - Crow and Mange (1965) developed a method to estimate the inbreeding coefficient (F) through an ingenious surname analysis. Such formulations assume a regularity of transmission of surnames, monophyletism, and random occurrence of consanguineous marriages. Accordingly, the ratio of isonymous partners to F of the offspring is equal to 4. Nevertheless, genealogy analyses show that the consanguineous marriages do not necessarily occur regularly. Therefore the isonymy analysis gives a misestimation of the inbreeding coefficient, depending on the prevailing form of nonrandomness. We suggest a small correction to the formulation in situations when pedigree information is available. The weighted mean of the ratio of isonymous partners to F of the known consanguineous marriages is suggested as a way to improve the formulas. The technique was applied to a northeastern Brazilian sample, and the results agree well with those of bioassays and therefore provide an apparently more realistic estimate of the inbreeding coefficient by isonymy. PMID- 1916746 TI - Pathology of the fallopian tube, broad ligament, peritoneum, and pelvic soft tissues. PMID- 1916747 TI - Selected topics in the pathology of the vagina. PMID- 1916748 TI - Advances in the pathology of intersex conditions. PMID- 1916749 TI - Academic manpower survey of 1990: I. Descriptors of departments of pathology in the United States (from the Joint Task Force on Pathology Manpower ASCP/CAP/APC). AB - A survey of chairmen of United States departments of pathology (97% response rate) augmented with data from the Association of American Medical Colleges shows that roughly two thirds (65%) of departmental faculty are physicians, the great majority of whom are pathologists. Most of the remainder are persons with solely the PhD degree (26.4% of faculty). The composition of departments of pathology in terms of age, gender, ethnic origin, academic rank, and tenure status is also reported. In contrast to a comparable survey performed 5 years previously, the present report shows that in 1989, departments of pathology contained (1) 20.6% more faculty positions, (2) a greater proportion of faculty members with a PhD degree, (3) greater numbers of open positions, and (4) a probable increase in the proportion of faculty that are female and that are of an ethnic minority. PMID- 1916750 TI - Uterine stromal neoplasms: a clinicopathologic and DNA flow cytometric correlation. AB - Twenty-five uterine stromal neoplasms (five stromal nodules and 12 low-grade and eight high-grade stromal sarcomas) were studied to determine the correlation between clinicopathologic features, flow cytometric tumor DNA content and proliferative fraction, and patient outcome. Fifteen of the 20 sarcomas (five of them high grade) were confined to the uterus (stages I and II); the other five (two low grade and three high grade) extended outside the uterus (stages III and IV). Stromal nodules and low-grade sarcomas manifested diploid DNA content and low proliferative index. All stromal nodules and the majority of low-grade sarcomas pursued a benign clinical course. Two cases of low-grade sarcoma ran a malignant course; both patients had high-stage disease. Three of the high-grade sarcomas were diploid and five were aneuploid. All eight neoplasms demonstrated high proliferative index and seven ran a malignant course (four of five were stage I and three of three were stage IV). Three high-grade stage I tumors had a low mitotic rate but a high proliferative index and ran an aggressive course. All high-stage sarcomas were clinically aggressive, irrespective of their histologic classification or DNA characteristics. The proliferative index by flow cytometry may offer an objective adjunct in predicting the aggressive potential of a subset in low-stage neoplasms. PMID- 1916751 TI - Hepatic amyloidosis: morphologic differences between systemic AL and AA types. AB - The liver is almost universally involved in systemic amyloidosis. Patterns of topographic distribution of amyloid within the liver lobule have been recognized, but the reliability of using these for classification of amyloid type is in question. We examined 286 livers from cases of systemic amyloidosis obtained from autopsies at Los Angeles County-University of Southern California Medical Center, classifying them as AL or AA type by means of the potassium permanganate Congo red-staining method along with a specific anti-AA antiserum. Prior publications have asserted that deposition of secondary (AA) amyloidosis is limited to the vessels in the portal tract, constituting a "vascular" pattern, and that in primary (AL) amyloidosis the deposits exhibit a "sinusoidal" pattern in that they are seen along hepatic sinusoids as well as in portal vessels. We confirmed that AL amyloid involves the portal vessels as frequently as AA amyloid and that deposition occurred significantly more frequently in the portal stroma, the central vein, and the "sinusoidal" areas. However, we also found a "sinusoidal" pattern in 29 of 78 cases of secondary (AA) amyloidosis; in 14 of these, more than half of the sinusoidal spaces were replaced by amyloid deposits. We also noted that in 23 of the 29 AA amyloidosis cases with "sinusoidal" involvement, a "sago" pattern of distribution of amyloid in the spleen was present. No consistent association of a specific chronic inflammatory disease with "sago" spleen and "sinusoidal" deposits could be documented. We conclude that topographic distribution of amyloid within the liver lobule is not a reliable method of distinguishing AA from AL amyloidosis and that specific staining methods must be used if the physician is to be able to attempt modern therapeutic modalities. PMID- 1916752 TI - Fibrous hamartoma of infancy: an immunohistochemical and ultrastructural study. AB - Fibrous hamartoma of infancy is an uncommon lesion of uncertain histogenesis. Three cases were studied by light microscopy, electron microscopy, and immunohistochemistry. Two histologic variants are presented. Ultrastructurally, fibroblasts and myofibroblasts were found in the fascicular-fibroblastic areas while primitive mesenchymal cells were found in the immature-appearing regions. Vimentin positivity was noted in both areas, whereas desmin and actin positivity was found mainly in the fascicular-fibroblastic regions. The lesion appears to fulfill the criteria for its characterization as "hamartoma." PMID- 1916753 TI - Hypopharyngeal sebaceous carcinoma: a case report. AB - A hypopharyngeal squamous-cell carcinoma with sebaceous differentiation is reported. In the primary as well as the metastatic lymph nodes, the tumor showed basaloid, squamous, and sebaceous cells. In addition, immunostaining for S-100 protein and vimentin manifested scattered cells showing cytoplasmic processes suggesting myoepithelial cells. An exhaustive review of the literature revealed only one similar case previously reported. The probable origin from the minor salivary glands is discussed. PMID- 1916754 TI - Mycoplasmal infection in the kidneys of patients with acquired immunodeficiency syndrome. PMID- 1916755 TI - Joint CAP-RF and ASCP-RPS residency training statement: response of the Joint Task Force on Pathology Manpower. PMID- 1916756 TI - The accelerated graying of American pathology. PMID- 1916757 TI - Diagnosis of genetic disease using recombinant DNA. Third edition. AB - Recombinant DNA methodology has greatly increased our knowledge of the molecular pathology of the human genome at the same time as providing the means to diagnose inherited disease at the DNA level. Direct detection and analysis of a range of genetic defects are now possible using cloned gene or oligonucleotide probes or by direct sequencing of the disease gene(s). In addition, the use of restriction fragment length polymorphisms (RFLPs) within and around these genes as indirect genetic markers has not potentiated the tracking of disease alleles in affected pedigrees in cases where direct analysis was not feasible. RFLPs associated with linked anonymous segments may also be used not only to diagnose hitherto undetectable disease states, but also for chromosomal localization of the loci responsible. We present here an updated list of reports describing both the direct and the indirect analysis/diagnosis of human inherited disease; it is intended to serve as a guide to current molecular genetic approaches in diagnostic medicine. PMID- 1916758 TI - Increased SOD1 enzymatic activity and gene modifications in orangutans: evolutionary implications. AB - Superoxide dismutase CuZn (SOD1) enzymatic activity was measured in five orangutans (Pongo pygmaeus, PPY) and compared to that of man, chimpanzee, and gorilla. It was found to be increased by a factor of two in one orangutan (Ralfina) and by a factor of 1.5 in the four others. In situ hybridization of the SOD1 cDNA human probe showed a heterozygous intra-chromosomal rearrangement of pair PPY XXI, possibly an insertion, in Ralfina. Southern blotting showed that the SOD1 gene is modified in the three orangutans that were investigated and that a further modification of the 5'-end of the gene had occurred in Ralfina. The evolutionary implications of these observations are discussed. PMID- 1916759 TI - Studies on the phylogenetic conservation of the SRY gene. AB - A probe from a conserved motif of the SRY gene (sex-determining region Y), a prime candidate for the human testis-determinant, was hybridized to DNA from 23 species representing 5 vertebrate classes. Hybridization occurred in species with male or female heterogamety, in species with and without sex chromosomes and in those with temperature sex determination. Sex-specific signals were observed only in mammals. Conservation of sequences homologous with SRY through 400 million years of vertebrate evolution would indicate persistence of function. However, if SRY is the primary sex determinant in mammals, it is not clear that it has a similar function, or even one that is sex-related, in nonmammals. PMID- 1916760 TI - A 5'-truncated c-myc gene variant not associated with a risk of cancer. AB - By analyzing c-myc specific fragments from white blood cell DNAs of 98 gastric cancer patients and 46 control subjects, we observed 6 unexpected patterns due to presence of a variant c-myc gene in addition to the normal gene. Restriction enzyme mapping indicated that the variant c-myc gene was the result of a 5' deletion including the first exon and part of the first intron. The deleted region, non-coding for the functional c-myc protein, contains sequences involved in the regulation of transcription. We therefore analyzed the c-myc mRNAs from a subject carrying the truncated gene and from a subject homozygous for the normal gene in Northern blotting experiments: the mRNAs were indistinguishable, both qualitatively and quantitatively. Family analysis demonstrated that the truncated gene is inherited in a Mendelian fashion. Population studies showed that the allele, both in patients and in control subjects, reaches a polymorphic frequency (2.1% for the whole sample) and that it is not associated with a risk of cancer. PMID- 1916761 TI - "Spontaneous" FRA16B is a hot spot for sister chromatid exchanges. AB - Six heterozygous carriers of a fragile site at 16q22 were available for the current study. We demonstrated that the observed fragile site was a "BrdUrd sensitive" fra(16)(q22) or FRA16B, capable of spontaneous expression in some individuals (= "spontaneous" FRA16B). Significant differences either in spontaneous or in ethylmethane sulfonate (EMS)-induced sister chromatid exchange (SCE) frequencies were found between the fragile 16q22 site, whether expressed or not, and its homologous normal site. These data complement our previous findings on FRAXA and provide additional arguments indicating that fragility and SCE are variable cytogenetic expressions of the same DNA structural alteration. PMID- 1916762 TI - Two unrelated children with partial trisomy 1q and monosomy 6p, presenting with the phenotype of the Larsen syndrome. AB - Two unrelated children presented with similar clinical features (facial dysmorphism and multiple joint dislocations) suggesting the diagnosis of Larsen syndrome. Both carried an inherited unbalanced translocation resulting in partial trisomy 1q and partial monosomy 6p. Analysis of skin collagen from one of the probands disclosed a decreased alpha 1/alpha 2 chain ratio of collagen type I, increased thermal stability and increased hydroxylation of proline and lysine. The present findings suggest that, as a result of the chromosome rearrangements, both patients have a mutation on a gene involved in collagen production, located either on chromosome 1q or, more probably, on 6p. It is furthermore suggested that other cases of Larsen syndrome are the result of a similar mutation. PMID- 1916763 TI - Analysis of synaptonemal complexes in a heterozygous human male carrier of a reciprocal translocation involving an acrocentric chromosome: heterosynapsis without previous homosynapsis. AB - Silver-stained synaptonemal complexes in surface-spread pachytene nuclei from an oligospermic man, heterozygous for a reciprocal translocation involving an acrocentric chromosome, were analyzed by electron microscopy. Contrary to the classically expected configuration, nonhomologous pairing was observed with asymmetrical association of the lateral elements of the nonhomologous arms of the quadrivalents. A possible role of heterosynapsis in germ cell conservation is discussed. PMID- 1916764 TI - Methods for analysis of multiple cystic fibrosis mutations. AB - A large number of mutations causing cystic fibrosis (CF) have been reported. In an attempt to improve methods for genetic diagnosis and for heterozygote screening, we evaluated methods for efficient analysis of the delta F508, G542X, G551D, R553X, and N1303K mutations. We found that multiple mutations can be analyzed simultaneously using hybridization with allele-specific oligonucleotides. Alternatively all of these mutations can be detected by amplification of DNA followed by restriction enzyme digestion and analysis on polyacrylamide gels. A previously reported method for use of modified primers for DNA amplification to allow detection of virtually any single-base change by restriction enzyme analysis proved particularly useful. The common delta F508 mutation and three mutations in exon 11 were analyzed using a multiplex amplification reaction followed by double digestion with restriction enzymes and electrophoresis in a single lane on a polyacrylamide gel. In a sample of 439 CF chromosomes from North American Caucasians, the frequencies of various mutations were as follows: delta F508 = 75.8%, G542X = 2.7%, G551D = 3.2%, R553X = 1.4%, and N1303K = 1.4% for a total of 84.5% detection of CF chromosomes by analysis for these five mutations. PMID- 1916765 TI - Chromosomal localization of the human D3 dopamine receptor gene. AB - A novel dopamine D3 receptor gene that may be involved in psychiatric diseases has recently been characterized. It has been assigned to chromosome 3 by hybridization with a D3 receptor probe to human sorted chromosomes, and localized to band 3q 13.3 by in situ hybridization. PMID- 1916766 TI - Regional assignment of the human cell cycle control gene CDC2 to chromosome 10q21 by in situ hybridization. PMID- 1916767 TI - Glutathione S-transferase class mu in French alcoholic cirrhotic patients. AB - The lack of glutathione S-transferase mu (GST mu) was examined in 45 healthy French Caucasians and 45 alcoholic cirrhotic French Caucasians: microsamples of blood were taken and DNA amplified by the polymerase chain reaction. We have concluded that there is no relationship between this genotype and the development of alcoholic cirrhosis in these heavy consumers of ethanol. PMID- 1916768 TI - DNA-fingerprinting: a short note on mutation rates. PMID- 1916769 TI - Segregation of lymphocyte low molecular weight DNA and antinuclear antibodies in a family with systemic lupus erythematosus in first cousins. PMID- 1916770 TI - Preventing neonatal herpes? PMID- 1916771 TI - Genitourinary medicine, AIDS and the NHS Act: will contracting arrangements lead to contracted services? PMID- 1916773 TI - Clinico-pathological conferences. PMID- 1916772 TI - Microbiological, epidemiological and clinical correlates of vaginal colonisation by Mobiluncus species. AB - The microbiological and epidemiological correlates of vaginal colonisation by Mobiluncus species were examined among randomly selected women attending a sexually transmitted disease (STD) clinic. Women positive for Trichomonas vaginalis were excluded. Mobiluncus spp. were detected by Gram stained vaginal smear in 21% of 633 STD clinic patients, including 53% of those with and 4% of those without bacterial vaginosis (BV), as diagnosed by clinical criteria. Gardnerella vaginalis and Mycoplasma hominis detected by vaginal culture and Mobiluncus detected by vaginal Gram stain were each independently associated with BV after adjusting by logistic regression for the presence of sexually transmitted disease pathogens, gravidity, parity and number of lifetime sexual partners (p less than 0.001 for each organism). Bacterial vaginosis was negatively correlated with isolation of lactobacilli, yeast and herpes simplex virus. After adjusting for presence or absence of BV, women with Mobiluncus were more likely to harbour G vaginalis (odds ratio 5.6, 95% confidence interval 1.6 19.5), M hominis (OR 3.7, 95% CI 2.0-7.0) and Neisseria gonorrhoeae (OR 2.9, 95% CI 1.4-6.0) and less likely to harbour vaginal yeast (OR 0.4, 95% CI 0.2-1.0); were more likely to be black (OR 2.7, 95% CI 1.5-4.6), and to have been pregnant (OR 1.8, 95% CI 1.1-3.1); but after the adjustment for BV, vaginal colonisation by Mobiluncus was not associated with symptoms of odour, abdominal pain, menstrual irregularities, or with adnexal tenderness. In summary, Mobiluncus, Gardnerella vaginalis and Mycoplasma hominis were independently associated with a clinical diagnosis of bacterial vaginosis, and Mobiluncus was further associated with the presence of BV-associated microorganisms (M hominis and G vaginalis), N gonorrhoeae, black race, and gravidity. PMID- 1916774 TI - Sexually transmissible diseases in injecting drug users. AB - Self-reported histories of sexually transmissible diseases (STDs) and HIV serostatus were investigated as part of a study of HIV risk behaviour in a sample of 1245 Syndey injecting drug users (IDUs) (mean age 27.5 years) both in and out of treatment. A high lifetime prevalence of STDs was reported in both men and women. For male IDUs, the lowest reported lifetime prevalence of STDs was in heterosexuals, with bisexuals intermediate and homosexuals reporting the highest prevalence. HIV seroprevalence followed the same pattern. For women, bisexuals had the highest reported STD history, heterosexual women were intermediate and homosexual women reported the lowest prevalence. Over one third of the bisexual women reported having been involved in prostitution. These data indicate that over one third of IDU men and over half of IDU women reported at least one STD in their lifetime. The high lifetime prevalence of STDs in IDUs indicates that this group is at increased risk of sexual transmission of HIV, given the importance of STDs as a cofactor. Reducing the prevalence of STDs in IDUs is a possible additional strategy to diminish the spread of HIV among IDUs and from them to non IDU sexual contacts. PMID- 1916775 TI - The value of serum TPHA titres in selecting patients for lumbar puncture. AB - Between January 1981 and December 1989, 258 patients with positive syphilis serology underwent lumbar puncture. Nine patients had long-standing neurosyphilis and had lumbar punctures performed during the course of their follow-up. Of the remaining 249 only 12 demonstrated the presence of TPHA in the CSF. The serum TPHA titre for eight of these 12 patients, and seven of the nine (two having no titre reported) known neurosyphilis patients at the time of original diagnosis, was 1 in 5120 or more. The four remaining newly found CSF positive patients had serum TPHA titres of 1 in 2560. We suggest that a serum TPHA titre of 1 in 2560 or greater should be considered as a criterion when selecting patients for lumbar puncture, especially when there are no clinical signs or symptoms. PMID- 1916776 TI - Survey of the management of Chlamydia trachomatis infection of the cervix. AB - A questionnaire was sent to all genitourinary medicine (GUM) clinics in the United Kingdom. Physicians were asked whether women attending the clinics were routinely screened for Chlamydia trachomatis, what treatment was given and whether and how a test of cure (TOC) was carried out after treatment; 94.5% of clinics responded. Screening for chlamydia was not carried out routinely in 4.8% of clinics. Treatments and their costs varied widely between clinics; six antibiotics were prescribed in 35 different ways. Less than half the clinics used regimens compatible with the advice of the World Health Organisation (WHO) and the Centers for Disease Control (CDC). Antibiotics in larger doses and/or for longer durations than those known to be effective were prescribed in 85% of clinics. Unnecessary routine TOC were carried out by 86% of clinics in 29 different ways. Sixteen percent of clinics carried out TOC immediately after completion of therapy, which is inadvisable on technical grounds. There is a need to standardise and improve the treatment and follow-up of chlamydial infection in women attending GUM clinics. PMID- 1916778 TI - Techniques used in clinical immunology. PMID- 1916777 TI - The role of genito-urinary medicine in adolescent sexuality. AB - OBJECTIVE: To examine the sexual behaviour and the prevalence of sexually transmitted diseases among adolescent girls who attended the Genito-Urinary Medicine Clinic in Birmingham. DESIGN: Retrospective case control study. SETTING: The Genito-Urinary Medicine Clinic (Ward 19), General Hospital, Birmingham. SUBJECTS: 159 adolescent girls aged 13-16 years; 215 female clinic attenders older than 16 years and 55 male partners of the adolescent girls. OUTCOME MEASURES: Number of sexual partners; contraceptive practice, and prevalence of sexually transmitted infections. RESULTS: The number of sexual partners was similar among the girls and controls. More girls than controls did not use any form of contraceptives, 49% versus 33.5% (p less than 0.01). The prevalence of bacterial vaginosis and gonorrhoea was significantly higher in the girls than in the controls (p less than 0.05). Compared with the girls and controls, the male partners of the adolescents had more sexual partners, and a higher prevalence of sexually transmitted infections--92.7%, 78.6% and 76.7% in the males, controls and girls respectively. CONCLUSION: The adolescent girls were associating with older men who had many sexual partners, and a higher prevalence of infections. By targetting these girls and their partners for counselling and health education the genitourinary medicine specialty can play a significant and positive role in adolescent sexuality. PMID- 1916779 TI - Serotyping Neisseria gonorrhoeae: a report of the Fourth International Workshop. PMID- 1916780 TI - Hidradenitis suppurativa. PMID- 1916781 TI - Sexual attitudes, preferences and infections in Ancient Greece: has antiquity anything useful for us today? AB - Modern society bears a heavy burden of medico-social pathology particularly amongst its young. The size, nature and costs of the sexually transmitted disease element is now considerable and dwarfs such successes as have been achieved. In the belief that the structure of a society and the way that structure functions determines the size of its STD problem, a review of Ancient Greek society has been undertaken. Greek society, not least concerning all aspects of sex, was well ordered, frank and tolerant. Some of the areas of Greek society's structure and functioning which differ most markedly from ours, and seem to have determined a modest STD problem, are highlighted and discussed. Greek ideas that might be adapted to match today's needs are presented for consideration. PMID- 1916782 TI - Eminent venereologists 5: Carl Crede. PMID- 1916783 TI - Recurrent periurethral abscess. PMID- 1916784 TI - Non-gonococcal urethritis in men practising "safe" sex. PMID- 1916785 TI - Gastrointestinal obstruction associated with Chlamydia trachomatis. PMID- 1916786 TI - Value of performing biopsies in genitourinary clinics. PMID- 1916787 TI - Sexual assault of men: a series. PMID- 1916788 TI - Choosing equipment for colposcopy in genitourinary medicine. PMID- 1916789 TI - The diagnosis of prostatitis: a review. PMID- 1916790 TI - Metastatic cerebral lymphoma. PMID- 1916791 TI - Subcutaneous interferon alpha 2a combined with cryotherapy vs cryotherapy alone in the treatment of primary anogenital warts: a randomised observer blind placebo controlled study. AB - OBJECTIVE: To compare patient tolerance and treatment efficacy of subcutaneous interferon (IFN) alpha 2a plus cryotherapy versus cryotherapy alone in treatment of primary anogenital (AG) warts. DESIGN: Randomised placebo controlled observer blind study. Statistical analysis was by chi square and Mann Whitney U tests. PATIENTS: 60 patients with newly diagnosed AG warts. INTERVENTION: 29 and 31 patients were treated with subcutaneous IFN alpha 2a plus cryotherapy or placebo injections plus cryotherapy, respectively. MAIN OUTCOME MEASURES: Clinical presence or absence of AG warts. Patients wart-free at 8 weeks were asked to re attend at 12 weeks; those with persistent warts at 8 weeks were withdrawn from the study. RESULTS: At 8 weeks 60.7% (17/28 patients) of the IFN group and 67.9% (19/28 patients) of the placebo group were clinically wart-free (not significant); corresponding figures at 12 week review were 29.6% (8/27 patients) and 40% (10/25 patients) respectively (not significant). There was no difference in treatment response between males and females. Recurrence of warts at three month review, in patients cleared of warts at 8 weeks, was seen in 50% (8/16) and 37.5% (6/16) of patients in the IFN and placebo groups respectively (not significant). Multiple warts and the presence of perianal/anal canal warts, either alone or concurrent with warts on the genitalia, at first clinic attendance, were adverse prognostic indicators (p less than 0.001, and p = 0.05 respectively). Cervical human papilloma virus (HPV) infection, exophytic or subclinical, was present in 58.3% and 77.2% of females in the IFN and placebo groups respectively, at trial entry. Although these lesions were not directly treated, colposcopic resolution was seen in 12.5% of affected women, in both treatment groups, by the end of the 7 week treatment period. Systemic side effects were significantly more common in the IFN than in the placebo group, 50% versus 10.7% of patients (p less than 0.01). Severe influenza like symptoms occurred, after the first three injections only, in one patient treated with IFN; all other reported side effects were mild. CONCLUSIONS: Subcutaneous IFN alpha 2a combined with cryotherapy is no more effective than cryotherapy alone in the treatment of primary AG warts. The presence of multiple warts and perianal/anal canal warts are adverse prognostic indicators. PMID- 1916792 TI - Homosexual prostitution among male drug users and its risk for HIV infection. AB - OBJECTIVE: to assess whether male prostitution is an independent risk factor for HIV infection among male (intravenous and nonintravenous) drug users. DESIGN: a cross-sectional study. SETTING: various low-threshold methadone clinics and the sexually transmitted diseases clinic of the Municipal Health Service in Amsterdam and a drug-treatment centre in The Hague. PARTICIPANTS: 343 male intravenous drug users and 106 male non-intravenous drug users. MAIN OUTCOME MEASURES: characteristics concerning drug use behaviour, sexual behaviour, and sociodemography, related to prostitution and HIV-antibodies. RESULTS: of the 449 study participants, 88 (20%) reported a history of prostitution; no differences were found between intravenous and non-intravenous drug users. Younger age, West German nationality, and having had private homosexual sex contacts, were independent predictors of a history of prostitution. Independent predictors of HIV infection were (1) longer residency in Amsterdam; (2) having had predominantly homosexual private sex contacts; (3) longer duration of intravenous drug use; and (4) frequent needle sharing. CONCLUSION: no evidence was found to suggest that male prostitution in itself contributed to the risk of HIV infection. PMID- 1916793 TI - Epidemiology of penicillin resistant Neisseria gonorrhoeae. AB - OBJECTIVE: To study the epidemiology of Neisseria gonorrhoeae that exhibit both chromosomal and plasmid-mediated resistance to penicillin. MATERIALS AND METHODS: A total of 1589 strains of N gonorrhoeae isolated from patients attending St Mary's Hospital, London were tested for both their susceptibility to penicillin and for their auxotype and serotype. RESULTS: Of the 940 non-penicillinase producing N gonorrhoeae, 840 were considered penicillin sensitive (MIC less than or equal to 0.5 mg/l) and 100 were chromosomally-mediated resistant N gonorrhoeae (CMRNG), (MIC greater than or equal to 1.0 mg/l). Of the 649 penicillinase producing N gonorrhoeae (PPNG), 429 carried the 4.4 megadalton (MDa) penicillinase encoding plasmid and 220 carried the 3.2 MDa plasmid. CMRNG were predominantly serogroup IB (90%). PPNG with 3.2 MDa plasmid were the only group more often serogroup IA (58%) than IB (42%). Serovar IA-1/2 and requirement for arginine, hypoxanthine and uracil (AHU) were associated with increased susceptibility to penicillin whereas serovar IB-5/7 was associated with decreased susceptibility in nonPPNG. There was a significant difference in the distribution of the IA and IB serovars between PPNG carrying either the 4.4 MDa or 3.2 MDa plasmid. AHU and PAOU requiring strains were not found among PPNG and were uncommon among CMRNG. CONCLUSION: Some clear associations have been found but the pattern among PPNG appears more complex and in most instances could be related to clusters of a single strain over a short time span. PMID- 1916794 TI - Patterns of homosexually acquired gonococcal serovars in Edinburgh 1986-90. AB - AIM: The aim of this study was to observe the changes in gonococcal serovar pattern in homosexual men over a 5 year period. METHODS: All men who presented to the Genitourinary Medicine clinic at Edinburgh Royal Infirmary between 1986 and 1990 with homosexually acquired gonococcal infection were included in the study. Gonococcal isolates were serotyped and the temporal change in isolated serovars noted. RESULTS: Over the 5 year period 32 different serovars were associated with 175 homosexually acquired infections. There was a dynamic temporal change in the dominant serovars with a continual influx of new strains some of which become established in the community but most of which appeared only transiently. Rapid variation in incidence over time was observed for certain serovars while others remained at more constant levels. There was a marked association between certain serovars (Ae/Av; Back/Bropyt; Bacejk/Brpyut; Bacejk/Brpyust; Baejk/Brpyut) and homosexually acquired infection. CONCLUSIONS: Possible determinants for the patterns observed are discussed but the underlying mechanism is probably multifactorial. PMID- 1916795 TI - Chlamydia trachomatis in sexually active teenage girls. Factors related to genital chlamydial infection: a prospective study. AB - The incidence of new infections with C trachomatis was found to be 19%. Predisposing factors for a subsequent chlamydial infection were multiple partners, smoking and previous infection with C trachomatis. Girls with a spread cervical ectopy were not more likely to contract a chlamydial infection in one year than girls without an ectopy. Oral contraceptive use was not found to predispose for a chlamydial infection. PMID- 1916796 TI - Antibody in sera of patients infected with Trichomonas vaginalis is to trichomonad proteinases. AB - BACKGROUND: A recent report demonstrated the immunogenic character of the cysteine proteinases of Trichomonas vaginalis. It was of interest, therefore, to examine for the presence of serum anti-proteinase antibody among patients with trichomoniasis. METHODS: An immunoprecipitation assay was used involving protein A-bearing Staphylococcus aureus first coated with the IgG fraction of goat anti human Ig and then mixed with individual sera of patients to bind human antibody. These antibody-coated bacteria were then added to detergent extracts of T vaginalis. Bound immune complexes on S aureus were washed and solubilised for electrophoretic analysis on acrylamide copolymerised with gelatin for detection of proteinase activity. RESULTS: Sera from patients (50/50), but none from sera of normal, uninfected women, possessed IgG to numerous trichomonad cysteine proteinases. The presence of this serum anti-proteinase antibody disappeared after drug treatment and cure of patients of the T vaginalis infection. CONCLUSIONS: The commonality of the anti-proteinase antibody in the sera of patients with trichomoniasis provided evidence for the expression of the same repertoire of parasite proteinases during infection. These observations have important implications for the in vivo relevance of the proteinases and indicate that strategies to use a specific serum antibody response for diagnosis of this infection may be possible. PMID- 1916797 TI - Sexually transmitted diseases in homosexual males in Seville, Spain. AB - BACKGROUND AND METHODS: The absence of any official statistics on the prevalence of STD in homosexual men in Spain induced us to carry out a prospective study of new homosexual patients who consulted the STD Clinic of the School of Medicine in Seville, between January 1988 and December 1989. The aim of the study was to determine the prevalence of symptomatic and asymptomatic infections in this group of patients. RESULTS: 1805 patients were seen during the study period; 318 patients were homosexual of whom 309 agreed to participate in the study. Of the 309 homosexual men, 108 (35%) had symptoms and the remaining 201 (65%) were asymptomatic. In the symptomatic group the diagnoses were: syphilis 28 (25.9%); urethritis 40 (37%) (of these 40, 11 had Neisseria gonorrhoeae, five had Chlamydia trachomatis, five had Ureaplasma urealyticum, one had Herpes simplex virus and in 18 no pathogen was detected); genital herpes seven (6.4%). Eleven (10%) had concomitant infections. The following infections were found in the asymptomatic group: syphilis 23 (11.4%), N gonorrhoeae six (3%), C trachomatis two (1%), Herpes simplex virus one (0.5%). Antibodies against HIV were detected in 30 (9.6%) of the total group. CONCLUSIONS: Sexually transmitted diseases are common amongst homosexual men in Seville and many of these are asymptomatic. PMID- 1916798 TI - Fournier's gangrene of scrotum in a patient with AIDS. AB - Fournier's gangrene of the scrotum, a form of necrotising fasciitis, is a rare but potentially fatal disorder. Predisposing conditions include chronic alcoholism and diabetes mellitus, possibly as a result of impaired immunity. Fournier's syndrome, occurring in a patient with AIDS, is described. PMID- 1916799 TI - Acute infection with human immunodeficiency virus presenting with neurogenic urinary retention. AB - Several neurological presentations of acute primary infection with HIV have recently been described. A previously unrecognised presentation with neurogenic retention of urine and sacral sensory loss is reported. The case is discussed in the context of other neurological syndromes associated with seroconversion to HIV, and of other viral causes of acute retention of urine. The importance of considering the possibility of primary HIV infection in a wide range of self limiting neurological disorders is emphasised. PMID- 1916801 TI - Syphilis and HIV infection. PMID- 1916800 TI - Autoinoculation lupus vulgaris of the perineum. AB - The case of a young heterosexual male, with a 7 year history of an asymptomatic progressive plaque over the right side of the perineum is described, which 4 years later involved the left perineum and scrotal skin, indicating autoinoculation. The diagnosis of lupus vulgaris was made by strongly positive tuberculin test, histopathology, and a favourable response to a short course of intensive antitubercular therapy. PMID- 1916802 TI - Rising incidence of genital herpes in an STD clinic in north India. PMID- 1916803 TI - Screening for Chlamydia trachomatis in a Turkish population. PMID- 1916804 TI - Preventing neonatal herpes? PMID- 1916805 TI - Sexually transmitted diseases in rape victims. PMID- 1916806 TI - Analysis of the 5' flanking region of the human beta-glucuronidase gene. AB - We have sequenced 4.2 kb of the 5' flanking region of the human beta glucuronidase gene, compared this sequence to the 5' upstream sequence reported for the murine gene, determined the transcription start sites of the human gene, and studied expression of human minigene deletion constructs in COS cells. The 200 bp immediately 5' to the translation initiation codon have a high G + C content (72%) and contain no TATA box, two properties commonly associated with "housekeeping genes." The sequence 5' to -200 bp contains seven Alu repetitive elements which account for more than 50% of this flanking sequence. From deletion analysis of minigene constructs, 200 bp of 5' sequence appeared sufficient for maximal expression in transfected COS cells. S1 nuclease protection analysis showed that transcription initiates from a cluster of sites around -30 bp in all tissues examined. In some cases, a low but detectable level of transcription also initiates 126 bp upstream of the ATG. Inspection of the sequence surrounding both start sites revealed some similarity to the recently described "initiator" transcriptional control element (S.T. Smale and D. Baltimore (1989), Cell 57: 103 113). Comparison of the 5'flanking sequence with that available from the murine beta-glucuronidase gene reveals only one 28-bp highly conserved region, which surrounds the -126 start site. PMID- 1916807 TI - Mapping of the mouse 86-kDa heat-shock protein expressed gene (Hsp86-1) on chromosome 12 and related genes on chromosomes 3, 4, 9, and 11. AB - The HSP86 gene family in BALB/c, AKR/J, C58/J, and NFS/N inbred mice comprises an intron-containing expressed gene and, depending on the strain, two to four other HSP86-related members that are apparently processed pseudogenes. The expressed gene locus, Hsp86-1, was identified by its sequence identity with the mouse HSP86 cDNA coding region together with the presence of an intron at the same position as in the homologous human gene. Hsp86-1 was mapped 11.6 cM from the immunoglobulin heavy chain gene IgH on Chromosome 12 using an intersubspecies backcross. Two of the other loci that were common to all inbred strains tested, designated Hsp86-ps1 and Hsp86-ps2, were mapped to positions on Chromosomes 11 and 3, respectively. An HSP86-related locus specific to NFS/N and C58/J mice, designated Hsp86-ps3, was mapped on Chromosome 9. Also, an HSP86-related locus that was unique to NFS/N mice, designated Hsp86-ps4, was mapped to Chromosome 4. PMID- 1916808 TI - The properdin structural locus (Pfc) lies close to the locus for tissue inhibitor of metallothionine proteases (Timp) on the mouse X chromosome. AB - We have confirmed the assignment of the structural locus of the complement factor properdin (Pfc) to the mouse X chromosome and mapped it between monoamine oxidase A (Mao-a) and hypoxanthine phosphoribosyltransferase (Hprt) using a Mus spretus x Mus musculus interspecific backcross of 108 animals. The structural locus for murine tissue inhibitor of metallothionine proteases (Timp) could not be separated from properdin in a panel of 18 recombinant animals. By minimizing the number of double recombinants the following gene order was obtained: Otc-Mao-a (Pfc, Timp)-Hprt-Cf-9. The implications for comparative mapping of human and mouse X chromosomes are discussed. PMID- 1916809 TI - Localization of the xeroderma pigmentosum group B-correcting gene ERCC3 to human chromosome 2q21. AB - The human excision-repair gene ERCC3 was cloned after DNA-mediated gene transfer to the uv-sensitive Chinese hamster ovary mutant cell line 27-1, a member of complementation group 3 of the excision-defective rodent cell lines. The ERCC3 gene specifically corrects the DNA repair defect of xeroderma pigmentosum (XP) complementation group B, which displays the clinical symptoms of XP as well as of another rare excision-repair disorder, Cockayne syndrome. The gene encodes a presumed DNA and chromatin binding helicase, involved in early steps of the excision-repair pathway. ERCC3 was previously assigned to human chromosome 2 (L.H. Thompson, A.V. Carrano, K. Sato, E.P. Salazar, B.F. White, S.A. Stewart, J.L. Minkler, and M.J. Siciliano (1987) Somat. Cell Genet. 13: 539-551). Here we report its subchromosomal localization in the q21 region of chromosome 2 via somatic cell hybrids containing a translocated chromosome 2 and in situ hybridization with fluorescently labeled ERCC3 probes. PMID- 1916810 TI - Large-scale physical mapping within the region 22q12.3-13.1 in meningioma. AB - The lack of physical mapping data strongly restricts the analysis of the meningioma chromosomal region that was assigned to the bands 22q12.3-qter. Recently, we reported a new marker D22S16 for chromosome 22 that was assigned to the region 22q13-qter by in situ hybridization. Utilizing somatic cell hybrids we now sublocalized the marker D22S16 within the band region 22q12-13.1, thus placing it in the vicinity of the gene for the platelet derived growth factor (PDGFB). A physical map was established for the regions surrounding the PDGFB gene and the D22S16 marker. By means of pulsed-field gel electrophoresis (PFGE) D22S16 and PDGFB were found to be physically linked within 900 kb. We also identified two CpG clusters bordering the PDGFB gene. For the enzyme NotI, a variation of the PDGFB restriction pattern was found between different individuals. PFGE analysis of the two loci (PDFGB and D22S16) failed to identify major rearrangements in meningioma. PMID- 1916811 TI - Human chromosome 16 physical map: mapping of somatic cell hybrids using multiplex PCR deletion analysis of sequence tagged sites. AB - Physical mapping of human chromosome 16 has been undertaken using somatic cell hybrid DNAs as templates for polymerase chain reaction (PCR) deletion analysis of sequence tagged sites (STSs). A panel of 29 somatic cell hybrids was analyzed, confirming and refining previous chromosome 16 breakpoint orders and distinguishing between the locations of breakpoints in new hybrids. Ten STS markers were coamplified in three multiplex reactions allowing the rapid, simultaneous deletion analysis of nine different loci. The locations of the protamine (PRM1), sialophorin (SPN), complement component receptor 3A (CR3A), NAD(P)H menadione oxidoreductase 1 (NMOR1), and calbindin (CALB2) genes were refined. PMID- 1916812 TI - Laser microdissection of the fragile X region: identification of cosmid clones and of conserved sequences in this region. AB - Laser microdissection has been used to dissect material from the X-chromosome region involved in fragile-X-linked mental retardation. After dissection, single chromosome slices corresponding to this fragile site were subjected to DNA amplification using either a vector ligation method (to provide known anchor sequences) or primer oligonucleotides corresponding to the ubiquitous Alu sequences. Amplified material was then cloned or, alternately, used to screen a gridded cosmid library. Eight cosmid clones identified in this way were regionally mapped using a panel of hybrid cell lines and shown to originate from a narrow interval centered on the fragile X site. Two clones are included in the approximately 6-cM interval defined by probes RNI (DXS369, 5 cM proximal) and VK21 (DXS 296, 1-2 cM distal) and which includes the fragile site, and at least one clone contains sequences conserved across species suggestive of a gene. This method combines the focused approach of microdissection and the convenience of obtaining cosmid (rather than small-insert) clones; it may be useful for studies of other defined chromosomal regions. PMID- 1916813 TI - A pseudogene on the X chromosome for the human trifunctional enzyme MTHFD (methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase formyltetrahydrofolate synthetase). AB - The human trifunctional folate-dependent protein MTHFD has been mapped to chromosome 14q24 and to the X chromosome was identified by screening an X chromosome-specific library. Amplification by the polymerase chain reaction (PCR) and sequencing of PCR products indicate that the sequence is an intronless pseudogene. PMID- 1916814 TI - Assignment of two of the translation initiation factor-4E (EIF4EL1 and EIF4EL2) genes to human chromosomes 4 and 20. AB - The eukaryotic translation initiation factor (eIF-4E) has recently been cloned from human, mouse, and yeast. This polypeptide is the rate-limiting component of the eukaryotic translation apparatus and is involved in the mRNA-ribosome binding step of eukaryotic protein synthesis. We have designed oligonucleotide primers to the 3' untranslated region of the gene encoding eIF-4E and specifically amplified the human gene in human/rodent somatic cell hybrids using the polymerase chain reaction. By this method, one of the human eIF-4E genes (EIF4EL1, eukaryotic translation initiation factor 4E-like 1) has been mapped to human chromosome 4qter-4p15. In addition, we have localized a second eIF-4E gene (EIF4EL2, eukaryotic translation initiation factor 4E-like 2) to human chromosome 20 by Southern blot analysis of mapping panels established from human/rodent somatic cell hybrids. PMID- 1916815 TI - The gene for von Recklinghausen neurofibromatosis (NF1) maps to the pericentromeric region of chromosome 17 in Chinese families. AB - Linkage analysis of six Chinese families with neurofibromatosis type 1 (NF1) confirms the location of the NF1 gene to the region of the proximal long arm of chromosome 17, as in Caucasian populations. The diagnosis of NF1 was made according to internationally accepted criteria. The markers used were D17S71, D17S58, D17S33, and EVI2A. The overall odds in favor of NF1 lying within this linkage group in the families studied are over 150,000:1, with a maximum location score of 5.112 for the interval D17S58-EVI2A. PMID- 1916816 TI - Evidence that descendants of three founders constitute about 25% of hemophilia B in the United States. AB - In our sample of 160 consecutive Caucasian hemophiliacs, 14 (9%) had a G----A transition at bp 10,430 that substitutes serine for glycine 60 in the first EGF domain of the factor IX molecule. Each of these hemophiliacs had clinically mild disease. Haplotype data and familial pedigrees indicate that 12 of these hemophiliacs are likely to be related to a common ancestor. The 13th and 14th patients possess different haplotypes and thus represent independent origins of the mutation. In addition, we have screened these 160 hemophiliacs for the previously reported mutations resulting from founder effects at IIe397----Thr and Thr296----Met. Herein we report an additional nine hemophiliacs with the mutant Thr397 allele and five additional hemophiliacs with the mutant Met296 allele. Haplotype data for these 14 hemophiliacs support the original founder effect hypotheses for these mutations. In total, the above three mutations are found in 44 of the 160 seemingly unrelated Caucasian hemophiliacs (28%). The sample includes patients from all regions of the United States and Ontario, Canada. Descendants of these three founders comprise approximately two-thirds of the missense mutations found in our sample of Caucasian hemophiliacs with clinically mild disease. PMID- 1916817 TI - Localization of the gene for the DNA-binding protein AP-2 to human chromosome 6p22.3-pter. AB - A variety of cellular proteins bind to cellular and viral enhancer elements. One such factor, known as AP-2, is a 52-kDa transcription factor identified by its interaction with the SV40 and metallothionein enhancers. In addition, it has been found that AP-2 binds to the SV40 T-antigen. AP-2 activity is mediated by both the state of cellular differentiation and changes in signal transduction pathways, suggesting a potential role of AP-2 in the regulation of diverse cellular processes. As part of an effort to examine the chromosomal organization of cellular genes encoding transcription factors, we report the mapping of the gene encoding AP-2 to human chromosome 6p22.3-24 by analysis of somatic cell hybrids and in situ hybridization to chromosomes. PMID- 1916818 TI - Report of the chromosome 5 workshop. PMID- 1916819 TI - An 18-locus linkage map of the pericentromeric region of the human X chromosome: genetic framework for mapping X-linked disorders. AB - We report a high-resolution genetic linkage map of the region Xp11.4 to Xq13.3, spanning the centromere of the X chromosome and encompassing approximately 30 cM. This 18-locus map is composed of 11 intervals that are spaced on average about 3 cM apart. Markers incorporated into the map together detect 19 distinct polymorphisms and include five genes (TIMP, SYP, AR, CCG1, PGK1), the OATL1 cluster, the hypervariable locus DXS255, the centromeric locus DXZ1, and 10 other anonymous DNA segments. Given that this map spans roughly one-fifth of the length of the X chromosome and includes many loci currently used in both diagnosis and mapping of X-linked disorders, it should be useful for genetic counseling and for guiding efforts to clone disease genes in this region. PMID- 1916820 TI - The generation of a library of PCR-analyzed microsatellite variants for genetic mapping of the mouse genome. AB - Forty-three sequences containing simple sequence repeats or microsatellites were generated from an M13 library of total genomic mouse DNA. These sequences were analyzed for size variation using the polymerase chain reaction and gel electrophoresis without the need for radiolabeling. Seventy-two percent of the sequences showed allelic size variations between different inbred strains of mouse and the wild mouse, Mus spretus; and 53% showed variation between inbred strains. Thirty-seven percent were variant between B6/J and DBA/2J, and 81% of these were resolved using minigel agarose electrophoresis alone. This approach is a useful way of generating the large number of variants that are needed to create high resolution maps of the mouse genome. PMID- 1916821 TI - Physical mapping of the human carbonic anhydrase gene cluster on chromosome 8. AB - A cluster of genes encoding the three cytoplasmic carbonic anhydrase isozymes CAI, CAII, and CAIII lie on the long arm of chromosome 8 (8q22) in humans. These genes have been mapped using pulsed-field gel electrophoresis. The genes lie in the order CA2, CA3, CA1. CA2 and CA3 are separated by 20 kb and are transcribed in the same direction, away from CA1. CA1 is separated from CA3 by over 80 kb and is transcribed in the direction opposite to CA2 and CA3. The arrangement of the genes is consistent with proposals that the duplication event which gave rise to CA1 predated the duplication which gave rise to CA2 and CA3. The order of these three genes differs from that suggested for the mouse based on recombination frequency. PMID- 1916822 TI - A class I jumping clone places the HLA-G gene approximately 100 kilobases from HLA-H within the HLA-A subregion of the human MHC. AB - By the combination of cosmid cloning, chromosomal jumping, and pulsed-field gel electrophoresis (PFGE), we have fine-mapped the HLA-A subregion of the human major histocompatibility complex (MHC). Through the isolation of a class I jumping clone, the Q alpha-like HLA-G class I gene has been placed within 100 kb of HLA-H. The tight physical linkage of these class I genes has been further supported by hybridizing PFGE blots with locus-specific probes. It has been found that both of the above class I genes are linked to HLA-A, with HLA-H residing no more than 200 kb from the HLA-A gene. These data support the possible existence of a Q alpha-like subregion composed of nonclassical HLA class I genes within the human MHC linked telomerically to the HLA-A locus. PMID- 1916823 TI - Physical mapping of two loci (D9S5 and D9S15) tightly linked to Friedreich ataxia locus (FRDA) and identification of nearby CpG islands by pulse-field gel electrophoresis. AB - The Friedreich's ataxia locus (FRDA) has recently been mapped to 9q13-q21 by tight linkage to D9S15 and D9S5 loci. The present lack of recombination between these loci precludes further genetic mapping and suggests that the distances involved are in the megabase range. We have established a 1-Mb map around loci D9S15 (defined by probe MCT112) and D9S5 (defined by probe DR47) and found that they are at most 260 apart. Six rare cutting site clusters were found in a 450-kb segment containing both loci. Three clusters were completely unmethylated in two cell lines tested and might correspond to CpG islands flanking transcribed sequences. Cosmid mapping of a 52-kb region around D9S5 and pulse-field gel electrophoresis analysis showed the presence of three other CpG clusters that were partially or completely methylated. Two of them were present in the cosmid clones available and were associated with sequences conserved in other vertebrate species. The CpG islands and conserved sequences presented here can be used to search for genes defective in Friedreich's ataxia. PMID- 1916824 TI - Linkage mapping and fluorescence in situ hybridization of TCTE1 on human chromosome 6p: analysis of dinucleotide polymorphisms on native gels. AB - Highly informative dinucleotide repeat polymorphisms were identified at the T complex-associated-testes-expressed-1 (TCTE1) locus on human chromosome 6p. Electrophoresis of single-stranded DNA on native gels facilitated the analysis of the dinucleotide polymorphisms. Linkage mapping positions this marker midway between the centromere and HLA with recombination fractions as follows: D6Z1-0.21 TCTE1-0.24-HLA. Two-color fluorescence in situ hybridization places TCTE1 proximal to CRIL171 (D6S19). Together, linkage and in situ hybridization indicate that the order of the loci is D6Z1-D6S4-D6S90-TCTE1-D6S19-D6S29-HL A-telomere. A sequence tagged site (STS) was established, and three yeast artificial chromosome (YAC) clones were identified for the TCTE1 locus. PMID- 1916825 TI - Isolation and characterization of two human H1 histone genes within clusters of core histone genes. AB - Two human H1 histone genes, termed H1.3 and H1.4, were isolated from two cosmid clones. The H1.4 gene is associated with an H2B gene, whereas genes coding for all four core histones are located in the vicinity of the H1.3 gene. This cluster arrangement was found both in the two cosmid clones and on overlapping bacteriophage clones isolated from an EMBL3 library. In continuation of our previous analysis of two human H1 genes, this analysis raises the number of completely sequenced H1 histone genes within clusters of core histone genes to four. PMID- 1916826 TI - Porcine SINEs: characterization and use in species-specific amplification. AB - A porcine repetitive DNA sequence has been isolated from an intron of the glucose phosphate isomerase gene. The copy number of this and related sequences was estimated to be approximately 10(5) copies per genome. The sequence possesses all the characteristics of short interspersed elements (SINEs) described in other mammals: The repeat is 300 bp in length, has an poly(A)stretch, and contains insertion duplication sites. Homology to seven other porcine sequences, which also have the characteristics of SINEs, has been demonstrated. Primer oligonucleotides, based on conserved regions in the SINE sequences, have been synthesized. Using these primers, PCR-mediated specific amplification of porcine sequences was demonstrated from pig x mouse and pig x hamster hybrid cell lines. Cloning and sequencing of some amplified porcine sequences verify that the sites of priming are SINE sequences. PMID- 1916827 TI - The construction of human somatic cell hybrids containing portions of the mouse X chromosome and their use to generate DNA probes via interspersed repetitive sequence polymerase chain reaction. AB - Interspersed repetitive sequence polymerase chain reaction (IRS-PCR) has become a powerful tool for the rapid generation of DNA probes from human chromosomes present in rodent somatic cell hybrids. We have constructed a somatic cell hybrid containing a major portion of the mouse X chromosome in a human background (clone 8.0). IRS-PCR was developed for the specific amplification of mouse DNA using either of two primers from the rodent-specific portion of the murine B1 repeat. Amplification was subsequently performed with clone 8.0 and a subclone, 8.1/1, which retains a small murine X-chromosomal fragment including Hprt and the Gdx locus. A total of 15-20 discrete PCR products ranging in size from less than 500 to greater than 3000 bp were obtained from clone 8.0 with each primer. In clone 8.1/1, a subset of these bands plus some additional bands were observed. Nine bands amplified from clone 8.1/1 have been excised from gels and used as probes on Southern blots. All of the fragments behaved as single-copy probes and detected domesticus/spretus variation. They have been regionally mapped using an interspecific backcross. The probe locations are compatible with those of markers known to be present in clone 8.1/1. These results demonstrate the feasibility of this method as applied to the mouse genome and the high likelihood of generating useful DNA probes from a targeted region. PMID- 1916828 TI - A deletion in the amelogenin gene (AMG) causes X-linked amelogenesis imperfecta (AIH1). AB - Amelogenesis imperfecta is characterized by the defective formation of tooth enamel. Here we present evidence that the X-linked form of this disorder (AIH1) is caused by a structural alteration in one of the predominant proteins in enamel, amelogenin. Southern blot analysis revealed a deletion extending over 5 kb of the amelogenin gene in males with the hypomineralization form of the AIH1. Carrier females were heterozygous for the molecular defect. The deletion appears to include at least two exons of the amelogenin gene and the extent of the deletion was verified by PCR analysis. The mutation was shown to segregate with the disease among 15 analyzed individuals belonging to the same kindred. Our results link a defect in the amelogenin gene to the abnormal formation of enamel. We thus conclude that the amelogenin protein has a role in biomineralization of tooth enamel. PMID- 1916829 TI - Physical mapping of yeast artificial chromosomes containing sequences from the human beta-globin gene region. AB - The recently developed technique for cloning genomic DNA fragments of several hundred kilobases or more into yeast artificial chromosomes (YACs) makes it possible to isolate gene families while preserving their structural integrity. We have analyzed five independent yeast clones identified by PCR screening using oligonucleotides derived from the adult human beta-globin gene. Analysis of the five clones containing YACs by conventional and pulsed-field gel electrophoresis revealed that all of the clones include a YAC with sequences from the adult beta globin gene as expected. One of the clones contains multiple, unstable YACs. Two other clones carry single YACs in which there are at least two unrelated human genomic inserts. The remaining two clones contain single YACs, 150 and 220 kb in size, that contain the entire beta-globin gene family and flanking regions in a single, structurally intact genomic fragment. These should prove useful in future studies of the regulation of expression of genes in the beta-globin gene cluster. PMID- 1916830 TI - Research in health education and promotion. PMID- 1916831 TI - Research and health education. PMID- 1916832 TI - Integrating qualitative and quantitative evaluation methods. PMID- 1916834 TI - Listen and you will be heard: the importance of the consumer in the development of mass media material. PMID- 1916833 TI - Findings from formative evaluations. The health education components of the control of diarrhoeal disease programmes in five American countries. PMID- 1916835 TI - Health education theories and research for AIDS prevention. PMID- 1916836 TI - Evaluating the quality of health education programmes. Some comments on methods and implementation. PMID- 1916837 TI - Policy paper. Health education in preventing tobacco use. PMID- 1916838 TI - The contribution of the IUHE to the evolution of key areas in health education. Forty years in perspective. PMID- 1916839 TI - Health--united efforts. PMID- 1916841 TI - Education for a better quality of life. PMID- 1916840 TI - Health education: historic windows of opportunity. PMID- 1916842 TI - "Meeting global health challenges". PMID- 1916843 TI - Towards positive health education. PMID- 1916844 TI - An informational perspective on skill transfer in human-machine systems. AB - Differentiation of perceptual invariants is proposed as a theoretical approach to explain skill transfer for control at the human-machine interface. I propose that sensitivity to perceptual invariants is enhanced during learning and that this sensitivity forms the basis for transfer of skill from one task to another. The hypothesis implies that detection and discrimination of critical features, patterns, and dimension of difference are important for learning and for transfer. This account goes beyond other similarity conceptions of transfer. To the extent that those conceptions are specific, they cannot account for effects in which performance is better following training on tasks that are less rather than more similar to the criterion task. In essence, this is a theory about the central role of low-dimensional informational patterns for control of behavior within a high-dimensional environment, and about the adjustment of an actor's sensitivity to changes in those low-dimensional patterns. PMID- 1916845 TI - Recombination of automatic processing components: the effects of transfer, reversal, and conflict situations. AB - This research was conducted to evaluate the effects of compatible and incompatible automatic processes on performance. Subjects were trained for 8400 trials of consistent mapping practice in a semantic category visual search task and then transferred for 2352 trials to conditions that utilized the trained component processes in various ways. Results indicate that if the components were reused in a compatible fashion (target and distractor transfer), there was positive transfer. Target and distractor reversal resulted in equivalent and severe performance disruption that persisted for the entire retraining period. Target conflict produced disruption equivalent to the reversal conditions. Distractor conflict resulted in less initial disruption, which dissipated before the end of the retraining period. The results are discussed in terms of agreement with strength-theoretic views of visual search and in terms of practical training and retraining issues. PMID- 1916846 TI - Affinity repertoire of monoclonal antibodies obtained by primary or secondary in vitro immunization. AB - The effect of the antigenic dose (1 ng-10 micrograms DNP-KLH/ml) on affinity constants of monoclonal antibodies produced by in vitro immunization was investigated. A statistically significant (p = 0.0000) trend could be demonstrated since the higher antigen concentration that was used during the five day culture the lower was the obtained Kass value. The range of affinities of the IgM monoclonal antibodies was similar to what was obtained from IgM antibodies produced by in vivo immunizations. However, the combination of a primary in vivo immunization followed by a secondary in vitro stimulation schedule resulted in an antigen dependent generation of high affinity isotype switch variants, exhibiting even higher affinities compared to monoclonal antibodies produced from only in vivo immunized animals. These results demonstrate that it is possible to elicit both an antigen-driven primary or secondary response in vitro. PMID- 1916847 TI - Expression of genetically engineered immunoconjugates of lymphotoxin and a chimeric anti-ganglioside GD2 antibody. AB - Human lymphotoxin was genetically conjugated to the constant region of a human gamma 1 immunoglobulin gene at the end of either the second (CH2-LT) or third (CH3-LT) constant region domain. The altered heavy chain constant regions were combined in a plasmid vector together with the variable regions of a mouse anti ganglioside GD2 antibody 14.18 and the human kappa constant region. The resulting immunoconjugate constructs were expressed in transfected hybridoma cells and tested for both their antibody and lymphotoxin activities. The two constructs were assembled to varying degrees depending on whether the third heavy chain constant region was present. Both forms retained their ability to bind antigen and mediate ADCC but only CH3-LT was able to mediate the lysis of melanoma target cells in the presence of human complement. Lymphotoxin activity, as defined in a cytolytic assay with mouse fibroblasts, was found to increase significantly as a function of heavy chain assembly and to be equivalent to unconjugated lymphotoxin. Neither of the constructs were cytotoxic for antigen-bearing melanoma cells that are normally resistant to lymphotoxin and tumor necrosis factor alpha. Such immunoconjugates may prove useful in targeting cytokines to the site of antigen-bearing cells in vivo. In this case, as a means of eliciting an inflammatory response at the site of a solid tumor. PMID- 1916848 TI - A monoclonal antibody applicable for determination of C-peptide of human proinsulin by RIA. AB - BALB/c, (BALB/c x B10.A)F1 and (BALB/c x B10)F1 hybrid mice were immunized with C peptide of human proinsulin. The (BALB/c x B10.A)F1 hybrids were the best responders and yielded 3 hybridomas secreting specific monoclonal antibodies. One of them, C-PEP-01, bound the C-peptide with high affinity (Kas = 1.1 x 10(9) l/mol), cross-reacted fully with human proinsulin but not with insulin, glucagon or somatostatin and apparently recognized the regions of C-peptide comprising amino acid residues 8-13 and 25-31. A RIA system could be set up employing this monoclonal antibody suitable for estimation of C-peptide concentrations in a diagnostically useful range (1-50 ng/ml). PMID- 1916849 TI - Characterization of a monoclonal antibody against concanavalin A binding antigen of Aspergillus fumigatus. AB - A monoclonal antibody was produced against a Concanavalin A (Con A) binding major epitope of Aspergillus fumigatus using a novel method of immunization. The antigen was purified using monoclonal antibody affinity chromatography reacted with specific antibodies present in human sera. Both allergic bronchopulmonary aspergillosis and aspergilloma showed high levels of antibody, against this purified antigen, when compared to normal controls. Similar results were obtained when the monoclonal antibody was used in a capture antigen assay. The antibody reacted with several A. fumigatus extracts in rocket electrophoresis demonstrating a single precipitin arc, which disappeared when Con A intermediate gel was used. This monoclonal antibody demonstrated reactivity only with cytoplasmic components of hyphae and spores of A. fumigatus, when a colloidal gold was used as a probe in immunoelectron microscopy. PMID- 1916850 TI - Monoclonal antibodies monospecific to single-chain urokinase-type plasminogen activator (scu-PA). AB - Until now, single-chain urokinase-type plasminogen activator (scu-PA) could not be distinguished from urokinase (UK) by immunological methods. Therefore, in our study monoclonal antibodies (mAbs) specific for scu-PA were raised in mice. These mAbs proved to discriminate between scu-PA, UK and plasmin-activated scu-PA. The clones producing these mAbs could be cultivated in a serum-free medium. Furthermore, very pure preparations were obtained by a one-step purification procedure on protein-A-sepharose. The mAbs described provide a future potential for immuno-affinity chromatography and for the specific determination of scu-PA. PMID- 1916851 TI - Optimization of growth and secretion of human monoclonal antibodies by hybridomas cultured in serum-free media. AB - To facilitate the production and purification of human monoclonal antibodies, we evaluated the ability of human hybridomas to adapt to chemically defined-serum free media. From a panel of human hybridomas secreting antibody against serotype specific lipopolysaccharide determinants of gram-negative bacteria, the growth and secretion properties of the two hybridomas producing antibodies against two strains of Pseudomonas aeruginosa, 4-8KH15 and 4-10KH139, were analysed. Both clones did not grow in protein-free medium. However, it was possible to adapt them to serum-free media consisting of a basal medium supplemented with insulin, transferrin, ethanolamine, and selenite. Antibody secretion rates were equal (4 8KH15: 26-31 micrograms IgM/10(6) cells/day) or higher (4-10KH139: 58-90 micrograms IgM/10(6) cells/day) in serum-free media as compared to conventional serum-supplemented medium. Our studies suggest that adaptation of the described hybridomas to selected serum-free media results in an antibody production which is very high as compared with reports in comparable systems. The establishment of these conditions will significantly facilitate the production of large amounts of human monoclonal antibodies which is a prerequisite for a therapeutical application. PMID- 1916853 TI - Preliminary development of two predictive models for DNR patients in intensive care. AB - The purpose of this study was to identify which variables are the best predictors of a do-not-resuscitate (DNR) classification and develop a model to predict the nursing care required by DNR patients in the ICU. Data collected on DNR and non DNR patients included nursing care requirements, severity of illness, resource allocation and sociodemographic characteristics. One model identified the best predictors of a DNR classification in intensive care as the origin of admission and the severity of illness score on the day of admission to intensive care. The second model identified the best predictors of nursing care requirements for DNR patients in intensive care as the number of days spent in intensive care prior to the DNR order, the average daily resource allocation points after the DNR order, and the severity of illness score on the day the DNR order was designated. PMID- 1916852 TI - Production of human monoclonal antibodies in dialysis tubing. AB - Human x mouse hybridoma cells were grown in dialysis tubing (DT) to obtain large quantities of human monoclonal antibodies (MAb). Hybridoma cells were grown inside the DT, which was placed in a tissue culture flask containing medium. The medium inside the DT was supplemented with different additives which may be selected depending on the intended use of the MAb. About 10-50 times higher concentrations of immunoglobulin (Ig) were obtained after cultivation in DT compared to conventional tissue culture (CTC) for 2 days. The purity of the MAb was high which facilitated further antibody purification. Production of human MAb in DT proved to be excellent for evaluation studies in laboratory scale. It does not require expensive equipment and several hybridomas can be grown simultaneously. PMID- 1916854 TI - Homeless shelter policies for women in an urban environment. AB - A survey of shelters serving women in Chicago (N = 43) identified admission criteria, policies and services, estimated the number of homeless women in childbearing years served by the shelters, the number who were pregnant or mothers with children, and identified unmet health needs and health services provided. The majority (64%) of the women using shelters were African American and there was great variability in shelter policies. Women with male children more than seven years old, pregnant women and substance abusers were less likely to be admitted. PMID- 1916855 TI - Correlates of successful breastfeeding. AB - This study of factors related to success in breastfeeding used achievement motivation and information theories to develop the hypotheses. The sample (N = 150) were married, primigravidas, planning to breastfeed. Breastfeeding for at least six weeks was the criterion for success. Pregnant women's achievement motivation and level of information about breastfeeding were found to be positively related to success in breastfeeding. PMID- 1916856 TI - Nutritional support in HIV infection: a multilevel analysis. AB - Infection with the human immunodeficiency virus (HIV) and the development of the acquired immunodeficiency syndrome (AIDS) is a long-term process in many individuals. The progression of HIV disease is beginning to demonstrate many commonalities with other chronic diseases. Although research has not yet shown clear-out evidence that diet can make a difference in the course of disease in HIV-infected clients, nutrition should be viewed as an important component of holistic care for HIV-infected clients because: 1) wasting and symptoms of malnutrition are common problems associated with these clients; and 2) nutrition has proven to be a beneficial component of care in other chronic conditions. This paper uses the model developed by Winett, King and Altman (1989) to review nutritional support in HIV infection from a multilevel perspective ranging from personal psychology to institutional/societal controls. The author concludes that there is a potential benefit from integrating nutritional assessment, diagnosis and education into the holistic care of HIV-infected clients at the personal, interpersonal, organizational and societal levels. PMID- 1916857 TI - Telling stories: narrative approaches in qualitative research. AB - There is a new attention across disciplines to narrative knowing--the impulse to story life events into order and meaning. In this paper, narrative is presented as a framework for understanding the subject and interview data in qualitative research. Examples of narrative approaches are offered, narrative analyses are contrasted with other kinds of qualitative analyses, and truth in narratives is considered. PMID- 1916858 TI - Comparison of two schema for classifying nursing research. AB - To examine trends in nursing research during the last five years of the 1980s and to test the reliability and validity of two taxonomic schemes to classify nursing research, 811 abstracts from three years of a national nursing research conference (Council of Nurse Researchers, 1983, 87, 89) were reviewed and classified independently by three investigators. Taxonomies were research topics as categorized in the Sigma Theta Tau International Directory of Nurse Researchers (STT) and the Classification of Nursing-Related Dissertations (DISSER). More than half of abstracts addressed clinical topics, and clinical research topics increased significantly over time (p less than .001). At least two of the three raters agreed on coding for 62.8 percent of abstracts with STT schemes, 70.9 percent with DISSER scheme (p less than .01). Additional testing and standardization of taxonomies for nursing research is needed to improve reliability and validity. PMID- 1916860 TI - Deconstructing the dogma in nursing knowledge and practice. AB - The existence of dogma, the unquestioning adherence to authority and tradition, is well documented as a barrier to knowledge development. Numerous examples of dogma can be found in nursing, particularly in regard to the nature of nursing as a discipline and practice of nursing. While authority and tradition provide a foundation of stability and consensus, blind faith is to be avoided. In this paper, the critical examination of examples of dogmatic belief is encouraged so that clear and useful characterizations of the nature of nursing may be developed. PMID- 1916859 TI - Interviewing institutionalized elders: threats to validity. AB - In the course of an ethnographic study of an intergenerational Geriatric Remotivation Program in a Southeastern U.S. nursing home, we encountered difficulties in interviewing institutionalized elders that threatened the validity of the data. The purpose of this paper is to explicate the difficulties and to recommend strategies for overcoming them. Four main clusters of elder characteristics threatened the validity of data: (1) physical characteristics; (2) cognitive characteristics; (3) affective characteristics; and (4) personal characteristics. Problematic data were categorized as "insufficient," "unclear," "nice" and "emotionally charged." Strategies for increasing validity when interviewing impaired institutionalized elders included increasing the sample size, returning to the setting frequently, lengthening observation periods, recognizing the value of stories, recognizing the value of socializing, using videotapes, collecting both interview and observation data, and having elders view and respond to videotaped recordings. PMID- 1916861 TI - "Tugboat Annie:" nursing's hero of Pearl Harbor--Grace Lally (1897-1983). AB - In 1991 we will mark the 50th anniversary of the Japanese attack on Pearl Harbor. Few nurses know that the Chief Nurse aboard the USS Solace, the only hospital ship in port on that fateful day, played a critical role in caring for the survivors. Grace Lally's calm, professional manner, along with her sensitivity to the needs of her patients, her 12 nurses, and the crew of the Solace made her a hero. This study is an investigation of her role on December 7, 1941, and her contributions as a career military nurse. PMID- 1916862 TI - Physical and psychosocial effects of antepartum hospital bedrest: a review of the literature. PMID- 1916863 TI - Nurse Manners' guide to politically correct behavior. PMID- 1916864 TI - On mischief. PMID- 1916865 TI - Informative survey of nursing journals. PMID- 1916866 TI - The influence of feminist philosophy on nursing practice. PMID- 1916867 TI - [Chronic immunoproliferative syndromes]. AB - Immunoproliferative syndromes are etiologically unclear, rare diseases which involve polyclonal B- and/or T-cell proliferations and frequently develop into malignant non-Hodgkin-lymphoma. Typically, these diseases are characterized by lymphadenopathies, hepatosplenomegaly, general fatigue and autoimmune phenomena. Here we briefly outline 6 syndromes, two of which--the "pluripotential chronic immunoproliferative syndrome" (CPIS) and the "angioimmunoblastic lymphadenopathy" (AILD)--are discussed in more detail. We favor the notion that CPIS is a variant form of AILD clinically dominated by severe autoimmune hemolytic anemia. Both diseases share the high frequency of anti-cytoskeleton autoantibodies. PMID- 1916868 TI - [Reiter's disease in a patient with chronic recurring parotitis]. AB - We report a 30-year-old patient who suffered from an acute exacerbation of chronic parotitis followed by manifestation of Reiter's syndrome one month later. Clinical course of both symptoms were in favour of a connection between them. PMID- 1916869 TI - [The influence of the duration of infusion on the acute toxicity of amphotericin B. Comparison of two hour versus four hour infusions]. AB - A prospective, randomized, double-blind crossover study was performed to compare the incidence and severity of amphotericin-B-induced acute toxicity (chills, fever, nausea and vomiting) after two- and four-hour infusions in 33 leukemic patients with suspected or microbiologically proven systemic fungal infections. Each patient was treated in an alternating fashion of two- and four-hour infusions every other day. Toxicity was graded according to modified WHO criteria. Evaluation of 264 infusions revealed no difference between the two schedules neither in incidence nor severity of acute toxic reactions. These data indicate that amphotericin B given over 2 hours is equally well--or poorly (!)- tolerated than the four-hour regimen. PMID- 1916870 TI - [Clinical experiences with mefloquine in tropical malaria--a prospective study]. AB - The therapeutic effects and side effects of mefloquine in falciparum malaria were investigated in an open prospective trial involving 20 patients. None of them had a history of neurologic or psychiatric disorders. Mefloquine was given in a total dose of 1500 mg base. The cure rate was 100%, fever and parasitemia subsided within 3 days. Side effects were vomitus and nausea in 25% of the patients. No neurological or psychiatric disorders were observed. Mefloquine was shown to be a safe therapeutic agent in the dosage used. However, regular follow-up examinations should be done in short intervals because of the possibility of late neuropsychiatric side effects; the patients and their relatives should be informed about this fact. PMID- 1916871 TI - [Gamma-1 heavy chain disease with the demonstration of Bence-Jones proteins]. AB - We describe a 61-year-old patient suffering from gamma-1-heavy-chain disease (gamma 1-HCD) associated with Bence-Jones-lambda proteinemia and proteinuria. The analysis of the patients gamma 1-HCD protein (WIN) shows a deletion of the complete Fd fragment. The N-terminal seven amino-acid residue does not resemble any of the known immunoglobulin-heavy-chain variable regions. Unexpectedly, in PBL-DNA and in DNA from EBV-immortalized cells we found in addition to the expected predominantly rearranged Ig-lambda-light-chain gene a predominant rearrangement of an Ig-kappa gene. These findings show that the gamma-1-heavy chain disease of the patient involves a defective regulation of Ig-light-chain gene activation as well. PMID- 1916872 TI - [Uveitis: occurrence in rheumatic diseases and immunosuppressive therapy]. AB - In 13/53 patients with uveitis an associated rheumatic condition was found. An infectious etiology could be assumed in 3/53 cases. Methotrexate was used in noninfectious uveitis in 11/53 cases, who were refractory to high doses of systemic steroids: all improved, 5 patients achieved complete remission. PMID- 1916873 TI - [High dose 7S-immunoglobulin therapy in collagenoses. Clinical observations and effects on the lymphocyte subsets and immunoglobulin production]. AB - Therapy with 7S-immunoglobulins in 8 patients with various connective tissue diseases led to a decrease of clinical disease activity. In vitro experiments showed that treatment induces change of B-cell function. Significant quantitative alteration of relative lymphocyte subpopulations did not occur. CRP, C3c, C4 and circulating immune complexes tended to normalization. PMID- 1916874 TI - [Renal involvement in rheumatic (systemic) diseases: new diagnostic possibilities]. AB - Patients (pts) with rheumatoid arthritis (RA) may develop structural damage and functional deterioration of the kidney, where interstitial fibrosis and mesangioproliferative glomerulitis are seen most frequently. Compared to controls 80 pts with RA under various therapeutical regimes and 23 pts with SLE excreted immunoreactive membrane proteins of the proximal tubule at an increased rate. 30 out of 76 pts, but all with SLE, revealed a pathological pattern of proteinuria in SDS-PAGE. PMID- 1916875 TI - [Macrophage activity during high dose steroid pulse therapy and 7S-immunoglobulin administration in patients with collagenoses. Comparison with in vitro studies]. AB - Patients with connective tissue diseases show increased neopterin levels indicating the activation of the monocyte system. Corticosteroids reduce the release of neopterin in vivo and in vitro. After i.v. 7S-Ig administration neopterin increases in vivo transiently and decreases beyond the pretherapeutic levels. Addition of 7S-Ig to cell cultures reduces the macrophage activation. PMID- 1916876 TI - [Cotrimoxazole in Wegener's granulomatosis--a prospective study]. AB - During the last 3 years 34 patients with Wegener's granulomatosis (W. G.) were treated 37 times with co-trimoxazole (Co-trim). In 10 patients with locoregional disease the progression of W. G. could be stopped in each case. In 27 cases (24 patients) with generalized W. G. in complete remission achieved with cyclophosphamide and prednisolone (Cyc/Pred) a relapse occurred in more than 50% (14/27) of the cases. PMID- 1916877 TI - Bacterial lipopolysaccharide acts synergistically with selected macromolecular polyanions to induce MHC-nonrestricted cytotoxic cells. AB - We examined whether bacterial lipopolysaccharide, at a dose range extending to less than 1.0 ng/ml, would work with cofactors to induce MHC-nonrestricted cytotoxic cells. To this end, normal mouse splenocytes were cultured for 5 days with LPS and potential cofactors, after which the cells were tested for cytotoxic activity in short-term 51Cr-release assays. We found that LPS can act synergistically with the macromolecular polyanions, dextran sulfate and polyinosinic acid. The effector cells induced by LPS and polyanions showed characteristics of activated NK cells in that they were (1) cytotoxic for widely differing sources of tumor cells, (2) not inhibited by an anti-T cell receptor antibody, and (3) not removed by depletion of CD4+ or CD8+ cells. LPS was active at picogram concentrations when dextran sulfate was included. Exposure of splenocytes to LPS was necessary during the early phase of the 5-day culture, but as little as 1 h of exposure was required, whereas exposure to the macromolecular polyanions during either the first or the last 2 days of a 5-day culture with LPS was effective. As expected with LPS activity, the cytotoxic cell response was prevented by polymyxin B or by the use of splenocytes from LPS non-responder C3H/HeJ mice. Screening of the S. minnesota R mutants and other partial LPS structures revealed that lipid A was closely associated with LPS activity in this assay system and that at least one partially detoxified structure, a deacylated LPS, could substitute for native LPS. PMID- 1916879 TI - Recent state of cyclophosphamide-induced skin allograft tolerance in mice. PMID- 1916878 TI - Characterization of human lymphocytes separated from fetal liver and spleen at different stages of ontogeny. AB - Membrane markers on human lymphocytes separated from fetal liver and spleen were studied. Depending on the period of intrauterine development, a growing percentage of T- and B-lymphocytes (up to 16% and 45%, respectively) among spleen cells was seen, but in liver the number was low independent of the gestational age (T cells less than 10% and B cells less than 15%). The majority of early CD3+ spleen cells (21st-28th week) expressed TCR alpha beta but not TCR gamma delta, although a significant proportion of these cells was still lacking CD4, CD8, and CD5 differentiation antigens, suggesting their immaturity. Later spleen T cells (29th-36th week) expressed the phenotype as mature adult-type T cells (CD3+TCR alpha beta +CD4/8+CD5+). During ontogeny in fetal spleen, a growing number of B cells could be estimated without any changes in the proportion of subsets, expressing the different light and heavy chains. However, the proportion of CD5+ B cells decreased with gestational age. The results suggest that the functional immaturity of antenatal splenocytes could not be caused by dramatic phenotypical differences in comparison with adult-type splenic lymphocytes. PMID- 1916880 TI - Nomenclature for factors of the HLA system, 1990. PMID- 1916881 TI - HLA class I nucleotide sequences, 1991. AB - The HLA Class I sequences included in this compilation are taken from publications listed in the accompanying paper, Nomenclature for factors of the HLA system, 1990 and Nomenclature for factors of the HLA system, 1989. Where discrepancies have arisen between reported sequences the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments identity between residues is indicated by a hyphen (-). Unavailable sequence is indicated by a period (.). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number. PMID- 1916882 TI - HLA class II nucleotide sequences, 1991. AB - The HLA Class II sequences included in this compilation are taken from publications listed in the accompanying paper, Nomenclature for factors of the HLA system, 1990 and Nomenclature for factors of the HLA system, 1989. Where discrepancies have arisen between reported sequences the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments identity between residues is indicated by a hyphen (-). Unavailable sequence is indicated by an asterisk (*). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number. PMID- 1916883 TI - Sera but not immunoglobulins of ophthalmic Graves' patients stimulate human embryonal fibroblasts' biosynthetic activity in culture. AB - The retroocular connective tissue changes in the ophthalmopathy of Graves' disease are known, however, the mechanism which leads to the increase in fibroblast number and activity is poorly understood. Using human embryonal fibroblast monolayers, fibroblast biosynthetic activity in the presence of sera, immunoglobulin deprived sera or immunoglobulins of Graves' patients with and without ophthalmopathy has been measured. Both sera and immunoglobulin deprived sera of the ophthalmic Graves' patients caused a marked increase of protein synthesis and a moderate increase of the sulphated glycosaminoglycan synthesis of fibroblasts. The same stimulatory effect was not found when immunoglobulin in fetal calf serum was used instead of sera, though anti-fibroblast IgG-s were present both in the sera and separated immunoglobulin fractions, as it has been demonstrated in an ELISA system. We conclude that the sera of ophthalmic Graves' patients contains a factor which stimulates human embryonal fibroblasts' biosynthetic activity in culture; this factor is not an immunoglobulin. The system described here seems to be suitable for studying the accompanying connective tissue changes in Graves' disease. PMID- 1916884 TI - Alteration in natural defense activity against NK-susceptible B16 melanoma cells after treatment with Corynebacterium parvum. AB - We have investigated the effects of administration of C. parvum on host anti metastatic activity against B16 melanoma H-2L, a natural killer (NK) sensitive clone with a low expression of H-2b. The anti-metastatic activity was estimated by monitoring the following two points. One was the survival ratio at an early stage after an intravenous (iv) inoculation of radiolabeled B16 H-2L cells, the other was the formation of pulmonary metastases after iv injection with the tumor cells. Administration of C. parvum showed a biphasic change in the NK activity of the spleen cells and the peritoneal exudate cells (PEC) in mice. At an early phase (2-3 days) after administration of C. parvum, the NK activity of the spleen cells and PEC was significantly augmented. On the other hand, at a later phase (14 days) after C. parvum administration, the NK activity was deeply depressed. In correlation with NK activity of the mice treated with C. parvum, the anti metastatic activity of the hosts was augmented in the early phase, whereas a depressed level of anti-metastatic activity was observed in the late phase after administration of C. parvum. These results suggest that the modification of NK activity is a possible basis for modulation of anti-metastatic activity by C. parvum. PMID- 1916885 TI - HLA class I and II expression in rhabdomyosarcomas. AB - The expression of class I and II histocompatibility antigens was studied in 43 specimens of skeletal and in 36 specimens of cardiac muscle. Expression was also analyzed in the tumoral counterpart of striated muscle tissue, in 21 rhabdomyosarcomas (13 embryonic, 2 alveolar and 6 pleomorphic). Normal striated muscle showed very weak HLA class I antigen expression and no class II expression. The rhabdomyosarcomas showed increased class I expression, possibly related to malignant transformation of this type of tissue and with the degree of cellular differentiation. In our series of rhabdomyosarcomas, we observed class II neoexpression only in some HLA class I positive specimens, which was unrelated to the degree of cellular differentiation in these tumors. PMID- 1916886 TI - Immunogenetics of systemic lupus erythematosus in Spanish patients: differential HLA markers. AB - HLA-DR3 antigen included in the compound phenotype B18BfF1 (but not the one linked to the B8BfS compound phenotype) was found to be significantly increased in our SLE patients. It is remarkable that in our Southern-Mediterranean population, B18BfF1DR3 individuals (but not B8BfSDR3) are prone to SLE with renal disease, in contrast with other Northern European and Caucasoid populations. Also, patients with autoantibodies to Ro/La have a significant increase of the B8DR3 compound phenotype. Production of autoantibodies against Ro alone was associated to DR2 and production of anti-Sm/nRNP to DR3 (either B18BfF1 or B8BfS associated) only in the subgroup without renal disease. The distinctive HLA and autoimmune associations to SLE with and without renal disease suggests that both clinical forms may not share a common identical pathogenesis. PMID- 1916887 TI - Ontogeny and function of two non-lymphoid cell populations in the chicken embryo. AB - The purpose of the study was to determine what type of non-lymphoid cells develop in chicken embryos during ontogeny, and whether these cells are functional. To detect these cells, we used monoclonal antibodies specific to two groups of non lymphoid cells: CVI-ChNL-68.1, specific for mononuclear phagocytes, and CVI-ChNL 68.2, specific for a subpopulation of reticulum cells in spleen, liver and bursa. Monoclonal antibodies HIS-C7, HIS-C1, and HIS-C12, which are specific to leukocytes, B lymphocytes, and IgM respectively, were used to correlate the ontogeny of non-lymphoid cells and lymphoid cells. Mononuclear phagocytes and reticulum cells were detected in the liver, spleen, yolk sac, bursa, gut, and thymus at about the same time as leukocytes, but earlier than B lymphocytes. To determine whether mononuclear phagocytes and reticulum cells in spleen and liver absorb antigen, we injected embryos intravenously with colloidal carbon and the antigen FITC-Ficoll. In addition, acid phosphatase was used as a marker for phagocytic activity. Reticulum cells in the liver and spleen were functional from the first point of detection, whereas mononuclear phagocytes in the liver and spleen started to absorb antigen a few days after their development. PMID- 1916888 TI - Identification of amino acids in the V3 region of gp120 critical for virus neutralization by human HIV-1-specific antibodies. AB - The importance of the dependence on single amino acids in the V3 region of HIV-1 gp120 was evaluated for virus neutralization and antibody-dependent cellular cytotoxicity (ADCC). Synthetic overlapping 15-mer peptides and a set of omission peptides covering amino acids 301-317 were used. Sera from 29 HIV-1-infected individuals at different stages of disease were tested for neutralization, ADCC and specific IgG reactivity. Six HIV-1 neutralizing monoclonal antibodies (mAb) acted as controls. All mAb reacted with a region (amino acids 304-318) of gp120, previously shown to induce neutralizing antibodies. The amino acids essential for reactivity were identified to be within the sequence GPGR (amino acids 312-315). The importance of this region for occurrence of neutralizing antibodies in infected humans was investigated using the same set of peptides. Out of 29 individuals, 21 were found to have neutralizing antibodies in titres between 100 and 1000. Among the neutralization-positive sera, 17/21 (81%) reacted with amino acids 304-318, compared with only one of eight sera (13%) negative in neutralization. When any of the four amino acids G, P, G or R were deleted, the seroreactivity decreased considerably. The conserved sequence GPGR was therefore considered to be the most important for neutralization in this region in human sera as well. Thus, the conserved sequence GPGR in the V3 region of gp120 is critical for virus neutralization by human HIV-1-specific antibodies. PMID- 1916889 TI - Human immunodeficiency virus (HIV)-infected cells and free virus directly activate the classical complement pathway in rabbit, mouse and guinea-pig sera; activation results in virus neutralization by virolysis. AB - Since animal models of human immunodeficiency virus (HIV) infection are being used increasingly in determining various aspects of virus/host interaction and as models for virus expression, it will be important to assess any significant differences in anti-viral immune responses between animals and humans. Previous studies have shown that incubation of HIV with non-immune sera from several animal species results in virus neutralization, and that rabbit serum can lyse HIV-infected cells. The objectives of the current study were to evaluate the animal complement pathway(s) activated by HIV and HIV-infected cells and determine the mechanism by which complement could mediate viral neutralization. Incubation of HIV-infected cells with mouse, guinea-pig or rabbit sera resulted in cell-surface deposition of C3 fragments. Deposition of C3 fragments did not occur either in the presence of C4-deficient guinea-pig serum or in the absence of Ca2+, indicating that activation by infected cells occurred via the classical pathway. Neutralization of free virus was also mediated by the classical pathway since C4-deficient guinea-pig serum and Ca(2+)-chelated sera lacked activity. Serum treatment of virus resulted in release of HIV reverse transcriptase (RT), suggesting that neutralization occurred by C5b-9-mediated virolysis. RT was also released from simian immunodeficiency virus by animal complement. Antibodies in animal sera were not responsible for the classical pathway activation by free virus or HIV-infected cells. These results define several substantial differences between animal and human complement reactivity with HIV which could significantly affect the ability of HIV to replicate in animals, and which need to be considered in the assessment of animal models of HIV infection. PMID- 1916890 TI - Oral immunization with xenogeneic antibodies stimulates the production of systemic and mucosal anti-idiotypic antibodies. AB - The humoral and mucosal immune responses to oral immunization with xenogeneic antibodies were studied using an animal model in which female rabbits were fed daily doses of the MOPC-315 murine IgA antibody, and were mated during the course of the feeding programme. Serum and colostrum samples were assayed for the presence of anti-idiotypic antibodies by ELISA assay, before and after depletion of anti-IgA antibodies, by affinity chromatography using another murine IgA idiotype. It was shown that all animals responded to exposure to the MOPC-315 idiotype with the production of serum anti-murine immunoglobulin antibodies and that four of six animals produced serum anti-idiotypic antibodies. That the immune response included antibodies directed against the antigen-binding site was confirmed by competition ELISA assay. Mucosal IgG and IgA anti-immunoglobulin antibodies were present in milk from all antibody-fed rabbits tested, and IgA anti-idiotypic antibodies were detectable in the colostrum of one rabbit. The results provide some support for the hypothesis that human exposure to xenogeneic antibodies, most commonly bovine milk immunoglobulins, may provoke the production of anti-idiotypic antibodies, and that such exposure may lead to disturbances of immune regulation. PMID- 1916891 TI - Expression of a dietary protein in E. coli renders it strongly antigenic to gut lymphoid tissue. AB - Bacteria that colonize the intestinal mucosa elicit a strong mucosal immune response, whereas food antigens such as ovalbumin are very weakly immunogenic to the gut-associated lymphoid tissue. This may either be due to special physico chemical properties of bacterial substances versus proteins from animals and plants, or to stimulating properties of the bacteria on, e.g., antigen presentation, rendering all substances contained within bacteria antigenic. To test these hypotheses, ovalbumin was expressed in wild-type Escherichia coli and germ-free female rats were colonized with this strain. The systemic and mucosal antibody response of these rats was compared with that of rats given large amounts of dietary ovalbumin. Biliary IgA antibodies, which reflect the local IgA antibody production in the intestine, were only found in the rats colonized with ovalbumin-synthesizing E. coli. IgG antibodies in the bile were also only seen in these rats. We conclude that mucosal immunogenicity depends on the context in which a protein is presented to the gut-associated lymphoid tissue, rather than to special antigenic characteristics of the protein in itself. PMID- 1916892 TI - Maturation of the antibody response to a protein-coupled form of the organophosphorus toxin soman. AB - We have analysed the serum antibody response of BALB/c mice to the organophosphorus toxin soman coupled to the protein carrier keyhole limpet haemocyanin (So-KLH) and compared the specificity of the serum antibodies to that of hybridomas described previously. The relative inhibitory capacities of various soman analogues for serum antibodies correlated with those for the monoclonal antibodies. Our results also demonstrate that immune memory to this organophosphorus hapten is stable for greater than 1 year. Interestingly, maturation of the serum antibody response is accompanied by fine specificity changes resulting in increased binding to soman-protein conjugates but not in significant changes in binding to free hapten analogues of soman. This finding suggests that contributions made by the protein carrier or bridge structure, including those made by amino acid side chains involved in the linkage, may play a significant role in the maturation process of antibodies recognizing protein coupled organophosphorus haptens such as So-KLH. Structurally related but charge dissimilar organophosphate haptens such as nitrophenylphosphocholine were poorly recognized, even when conjugated to protein with the same diazophenyl linkage used to conjugate soman. This is consistent with maintenance of high specificity in the memory immune response to soman-coupled protein. PMID- 1916893 TI - Idiotype specific T-cell lines inducing experimental systemic lupus erythematosus in mice. AB - Immunization of mice with either antibodies bearing the 16/6 idiotype (16/6 Id) or anti-idiotypic antibodies against the 16/6 Id induces experimental systemic lupus erythematosus (SLE). We report here the establishment and characterization of 16/6 Id-specific T-cell lines from C3H.SW (H-2b) and BALB/c (H-2d) mice. Both lines proliferate specifically in response to the 16/6 Id in an H-2-restricted manner. The injection of 16/6 Id-specific T cells into syngeneic mice led to the development of experimental SLE. Furthermore, inoculation of the 16/6 Id-specific T-cell line derived from C3H.SW mice into the H-2 compatible C57BL/6 mice, which are non-responders to the 16/6 Id, induced experimental SLE. This report provides direct evidence for the role of idiotype-specific T cells in the induction of experimental SLE. PMID- 1916895 TI - Erythrocyte-reactive T-cell lines and clones from normal mice recognize serum derived antigens. AB - T-cell clones and cell lines which apparently respond to autologous (syngeneic) erythrocytes have been generated from the spleens of normal mice. The response showed considerable cross-reactivity with red blood cells (RBC) from other species, including chicken, and was 'heteroclitic' in that reactivity against some species of RBC, notably rat and monkey, was greater than to mouse. The clones were Thy-1+ L3T4+ Lyt-2- and recognized antigen in association with I-Ak or I-Ek. At least three specificities were identified on the basis of reactivity to crude lysates of mouse and rat RBC. One of the putative clones, M0.5/1/D2, showed a change in reactivity during culture, proliferating strongly against antigen-presenting cells (APC) without added erythrocytes. Analysis of the clones and lines using an I-Ak I-Ek expressing hybridoma, HB-98, has indicated that only one, M5/1/F5, was likely to be erythrocyte-specific; the remainder were responding to antigens present in foetal calf serum (FCS). The data demonstrate that apparent erythrocyte specificity can be a result of serum components being presented to T lymphocytes via red blood cells. PMID- 1916894 TI - Does staphylococcal enterotoxin B bind directly to murine T cells? AB - We have investigated the binding potential of staphylococcal enterotoxin B (SEB) to murine T cells using the induction of early activation events in Th1 and Th2 T cell clones in the absence of antigen-presenting cells (APC) as indicators of direct interactions between SEB and the T-cell receptor (TcR). We consistently found that concanavalin A (Con A) induced rises in intracellular free calcium as well as inositol phosphate accumulation in APC-free T-cell clones. However, SEB uniformly failed to induce either calcium fluxes or inositol phosphate turnover in Th1 and Th2 T-cell clones in the absence of APC. In addition, we have used proliferation assays to show that (i) T-cell clones prepulsed with SEB did not respond when APC were added, (ii) APC-independent T-cell clones responded to soluble anti-TcR antibodies but not to SEB in the absence of APC, and (iii) SEB coupled to Sepharose beads did not stimulate T-cell clones in the absence of APC. Taken together our results argue against SEB binding to the TcR without the participation of MHC class II molecules. PMID- 1916896 TI - Tumour necrosis factor-alpha induces translocation of protein kinase C in tumour necrosis factor-sensitive cell lines. AB - In this study we investigated whether the anti-proliferative effect of tumour necrosis factor-alpha (TNF-alpha) was associated with the activation of protein kinase C (PKC), using PANC-1 cells (TNF-alpha sensitive) and LoVo cells (TNF alpha resistant). In combination with 12-0-tetradecanoylphorbol-13-acetate (TPA), a potent activator of PKC, TNF-alpha caused marked inhibition of the growth of LoVo cells. Inhibition of PANC-1 cell growth by TNF-alpha was blocked by pretreatment with TPA for 24 hr, along with down-regulation of PKC activity. Intracellular translocation of PKC from cytosol to membrane was induced by TNF alpha treatment in PANC-1 cells but not in LoVo cells. PMID- 1916897 TI - Transcriptional and post-transcriptional mechanisms involved in the differential expression of LPS-induced IL-1 and TNF mRNA. AB - The amplification of cytokine mRNA following incubation of macrophages with inflammatory stimuli and protein synthesis inhibitors has been related to stabilization of labile mRNA species containing the 3'AUUUA consensus sequence. In the present study, cycloheximide-treated lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages had a five- to six-fold increase in tumour necrosis factor (TNF) mRNA when compared to parallel LPS-stimulated controls. Interleukin 1 beta (IL-1 beta) mRNA levels in these cells, however, were significantly lower than the LPS controls. The down-regulation of IL-1 beta by cycloheximide was not apparent for IL-1 alpha mRNA, which had a two- to three-fold increase in the LPS stimulated cycloheximide-treated macrophages. A similar profile was observed in vivo in which up-regulation of TNF, but not IL-1 beta mRNA, was apparent in mice administered cycloheximide plus LPS relative to LPS alone. Cycloheximide-treated LPS-stimulated macrophages demonstrated a significant increase in transcriptional activity for TNF, but not IL-1 beta, by nuclear run-on transcription assays and an increase in the amount of the nuclear binding factor NFKB when compared to LPS controls. The cycloheximide-mediated increase in TNF mRNA was also related to an increased stability of the TNF message, while no significant increase in stability was apparent in IL-1 beta mRNA. Therefore, the differential expression of TNF and IL-1 beta mRNA in cycloheximide-treated macrophages involves both transcriptional and post-transcriptional regulatory mechanisms. PMID- 1916898 TI - IL-8 causes in vivo neutrophil migration by a cell-dependent mechanism. AB - A dose-dependent neutrophil migration was observed following the injection of recombinant interleukin-8 (rIL-8) into rat peritoneal cavities. This finding contrasts with the inability of rIL-8 to induce neutrophil emigration into subcutaneous air-pouches. Pre-treatment of the animals with dexamethasone (0.5 mg/kg, s.c.) or depletion of the peritoneal resident cell population abolished the neutrophil migration induced by rIL-8 and by recombinant interleukin-1 beta (rIL-1 beta). Different from that which occurs with rIL-1 beta, neutrophil migration induced by rIL-8 was not enhanced by an increase in the peritoneal macrophage population. Transference of homologous total resident peritoneal cells to the air-pouch rendered this cavity responsive to the chemotactic effect of rIL 8 and potentiated the neutrophil migration induced by rIL-1. Our results show that both rIL-8 and rIL-1 beta are able to induce in vivo neutrophil migration by an indirect mechanism, dependent on resident cells. Neither macrophages nor lymphocytes seem to be involved in the rIL-8 chemotactic effect. However, peritoneal resident mast cells may be implicated in this mechanism. These cells, when stimulated in vitro by rIL-8, released a factor that when injected into peritoneal and air-pouch cavities induced neutrophil migration. PMID- 1916899 TI - Mast cell adhesion to fibronectin. AB - The MCP-5 murine mast cell line, as well as primary bone marrow-derived cultured mast cells (BMCMC), are demonstrated to bind to fibronectin, a ubiquitous adhesion protein of the extracellular matrix. BMCMC required activation by phorbol myristate acetate (PMA) to adhere to fibronectin, whereas MCP-5 displayed spontaneous adherence. The binding of both MCP-5 and BMCMC was dose dependent, with maximal adhesion at a fibronectin concentration of 20 micrograms/ml. The 120,000 molecular weight (MW) proteolytic fragment of fibronectin containing the RGDS cell attachment site was able to substitute for the native fibronectin molecule in promoting mast cell attachment. Mast cell adhesion to fibronectin, in addition, could be inhibited by the RGDS peptide alone. These data suggest that, in addition to the previously described mast cell-laminin interactions, mast cells also adhere to fibronectin, thus providing further insight into their tissue localization and possible roles in processes such as wound healing and fibrosis. PMID- 1916900 TI - The measurement of respiratory burst induced in polymorphonuclear neutrophils by IgA and IgG anti-gliadin antibodies isolated from coeliac serum. AB - The properties of IgA and IgG anti-gliadin antibodies from the serum of patients with coeliac disease have been compared. The antibodies were quantified by ELISA using microtitre plates coated with crude gliadin fractions. Their specificity was confirmed by immunoblotting. Heat-treated sera containing IgA antibodies stimulated chemiluminescence when added together with neutrophils to microtitre plates coated with crude gliadin. Sera containing only IgG antibodies were less efficient. When IgA and IgG were purified from a serum containing both classes of anti-gliadin antibodies, each of the preparations was able to stimulate neutrophil chemiluminescence in plates coated with gliadin. Although the yield of anti-gliadin antibody determined by ELISA was high, the ability of the purified immunoglobulins to stimulate neutrophil chemiluminescence was much less than that of the unfractionated serum. This loss of activity was shown to be due to the ability of each class of antibody to potentiate the activity of the other in the whole serum. PMID- 1916901 TI - Regulation of Forssman antigen expression during maturation of mouse stromal macrophages in haematopoietic foci. AB - During a trial to develop a monoclonal antibody (mAb) specific to stromal macrophages (M phi) in haematopoietic foci, we have created a mAb, designated F10, that stains the stromal M phi more selectively than any other mAb reported. As F10 was found to react with Forssman glycosphingolipid (GSL) specifically and to give clearer immunostaining than anti-Forssman GSL IgG, we have studied Forssman antigen expression during maturation of the stromal M phi in splenic haematopoietic foci using F10 and a system of allogenic bone marrow transplantation which allows us to know the turnover of the stromal M phi in vivo. C3H/He mice (H-2k) were lethally irradiated and intravenously infused with the bone marrow cells of BALB/c nu-nu mice (H-2d). Splenic frozen-sections and cytocentrifuge preparations of splenic haematopoietic clusters from the recipient mice were stained with F10 and with mAb against major histocompatibility class I antigens. H-2d-type stromal M phi began to appear in the haematopoietic clusters at Week 5 and they gradually replaced H-2k-type stromal M phi. The percentage of Forssman+ stromal M phi gradually decreased and reached a nadir at Week 6, when most stromal M phi were already of the donor type. At Week 8, however, Forssman+ stromal M phi levels returned to normal. The delayed expression of Forssman antigen on the stromal M phi in haematopoietic foci following genotypic conversion suggests that Forssman antigen is regularly expressed on the subpopulation of stromal M phi, which mature well under specific microenvironmental factors in vivo. PMID- 1916902 TI - Mucosal and systemic antibody formation in the rat after intranasal administration of three different antigens. AB - In order to study the role of nasal-associated lymphoid tissue (NALT) in the local nasal immune response, rats were immunized intra-nasally with either of the following trinitrophenylated (TNP) antigens; the thymus-dependent keyhole limpet haemocyanin (KLH), or the thymus-independent lipopolysaccharide (LPS), or with the particulate (thymus-dependent) sheep red blood cells (SRBC). Primary responses hardly occurred, while only TNP-KLH elicited a considerable secondary response. The major responding organ was the posterior cervical lymph node. Specific antibody-forming cells (AFC) occurred in the medulla and were mainly of the IgA or IgG isotype. Hardly any specific AFC were found in NALT or the surrounding mucosa. Intranasal immunization evoked no antibody response in the lung. Ample anti-TNP antibodies could be detected in the sera of animals, primed and boosted with TNP-KLH or TNP-LPS. No specific serum antibodies occurred after immunization with TNP-SRBC. The results are discussed in view of the immunological defence in the upper respiratory tract. PMID- 1916903 TI - The nature of immunoglobulin idiotypes and idiotype-anti-idiotype interactions in immunological networks. PMID- 1916904 TI - T lymphocyte participation in acute serum sickness glomerulonephritis in rabbits. AB - The extent and timing of glomerular T lymphocyte infiltration was studied in acute serum sickness (AcSS) glomerulonephritis (GN) in rabbits. AcSS was initiated by a single intravenous injection of bovine serum albumin (BSA). Rabbits developed circulating BSA anti-BSA immune complexes, and rapid immune elimination of the circulating antigen was associated with the deposition of immune complexes in the kidney and the onset of a diffuse endocapillary proliferative GN. On the day of immune elimination (defined as when less than 1% of the injected antigen remained in the circulation), rabbits developed significant proteinuria (98 +/- 36 mg/24 h; normal 14 +/- 1 mg/24 h, P less than 0.01), glomerular macrophage accumulation (44.3 +/- 21.1 macrophages per glomerulus [mac/glom]; normal 0.28 +/- 0.18 mac/glom, P less than 0.01), and a significant glomerular T lymphocyte influx (3.0 +/- 0.9 cells/glomerular cross section [c/gcs]; normal 0.47 +/- 0.13 c/gcs; P less than 0.005). On the day prior to immune elimination, increased T cells numbers were observed in some rabbits (2.4 +/- 2.1 c/gcs) together with a minor macrophage presence (7.6 +/- 3.6 mac/glom) and minimal proteinuria (17.6 +/- 3 mg/24 h). These studies demonstrate the influx of T lymphocytes together with macrophages at the onset of proteinuria in serum sickness nephritis and are consistent with a role for cell-mediated immunity in the pathogenesis of this lesion. PMID- 1916905 TI - Proceedings of the Australasian Society for Experimental Pathology, twenty-third annual meeting. 30 September-3 October 1991. Abstracts. PMID- 1916906 TI - Advances in transplantation immunology. Proceedings of a meeting held at the University of Aberdeen, 18-21 September 1990. PMID- 1916907 TI - Advances in transplantation immunology. PMID- 1916908 TI - Monoclonal and polyclonal antibodies: clinical aspects. AB - Over the years, the ways in which the antibodies ATG and OKT3 have been used in clinical transplantation have changed. ATG was first on the scene and has been used as initial immune suppression in certain forms of transplantation, of which cardiac transplantation is one good example. It has not been commonly used in renal transplantation, but there is evidence that this may be changing. The nephrotoxic side-effects of cyclosporin continue to cause anxiety, and high rates of initial non-function of kidney allografts have made early management difficult; this may have contributed to some early graft failures. There is currently interest in avoiding the use of cyclosporin initially by commencing immune suppression treatment with ATG, in an attempt to improve the immediate function rate of kidney grafts. When function is established, more conventional treatment schedules, usually with cyclosporin A, are introduced. ATG is also being incorporated in basic immunesuppressive regimes as part of multiple drug treatments. The hypothesis of multiple drug treatments is based on the idea that if a number of different immune suppressive agents are used, then the dose of each may be reduced, with minimisation of side-effects. This concept may be true, but the price may be that of an increased rate of malignancy in the long-term graft recipients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916909 TI - Monoclonal antibody therapy for the induction of transplantation tolerance. AB - There are three ways in which monoclonal antibodies could be used to facilitate the induction of tolerance to foreign tissues after organ transplantation. First, depleting monoclonal antibodies could be directed against the T cells responsible, thereby reducing their number and acting to non-specifically immunosuppress the patient. This is generally not sufficient to allow tolerance induction in the T cells which repopulate the periphery. Second, depleting monoclonal antibodies could be used to remove donor passenger leukocytes and antigen-presenting cells from the donor organ, which may both reduce immunogenicity and increase the chance of tolerance induction. Third, non depleting, but functionally blocking, monoclonal antibodies to T cell molecules such as CD4 and CD8 can allow the specific induction of transplantation tolerance in mouse models, an approach which might be applicable to man, not only for organ transplantation, but also in the treatment of autoimmune diseases. These three approaches are, in time, likely to complement each other in clinical practice. Monoclonal antibodies can be tailored to each approach by choosing appropriate specificities and isotypes, and further refinements can be made where necessary by making monovalent or humanised antibodies. The application of each of these approaches to clinical therapy is described. PMID- 1916910 TI - The blood transfusion effect: experimental aspects. AB - In some animal models of organ transplantation, notably the rat, preoperative administration of donor strain blood may produce long-term allograft survival even in the absence of adjunctive immunosuppressive therapy. The ability of blood transfusion to prevent rejection is highly dependent on the strain combination and type of graft, as well as the nature, dose and timing of transfusion. Although the effect is donor-specific, partial sharing of MHC and/or minor antigens between the blood and organ donor may be sufficient to prolong graft survival. The mechanisms underlying the enhancing effect of blood transfusion and other protocols which lead to specific unresponsiveness in the adult animal are undoubtedly complex and still poorly understood. In contrast to neonatal tolerance, where there is complete clonal deletion or anergy, lymphocytes from enhanced animals often show normal alloreactivity in vitro. Blood transfusion provokes an accelerated immune response to an allograft with rapid leukocyte infiltration of the graft and associated induction of class I and class II MHC target antigens. Moreover, graft infiltrating cells obtained from non-rejecting grafts in transfused recipients show levels of in vitro specific cytotoxicity equivalent to or in excess of those found in rejecting grafts. Despite the heightened cellular response provoked by blood transfusion, host regulatory mechanisms override the rejection response and there is substantial evidence for the existence in transfused animals of T cells with antigen specific suppressor activity. However, the site in the rejection process at which suppression is mediated is unknown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916911 TI - Alternative approaches for the induction of transplantation tolerance. AB - The immunosuppressive drugs currently in use in clinical transplantation are undoubtedly very effective at controlling graft rejection. However, their use is associated with a large number of side-effects, both immunological and non immunological, particularly in the longer term. From an immunological point of view, the major disadvantage of these agents is that their mode of action is immunologically non-specific, resulting in blanket or pan-immunosuppression of the recipient's immune system. Thus, not only is the recipient's immune response against the organ graft suppressed, but responses to all other antigenic stimuli such as viral infections are also prevented. The transplant recipient can therefore become severely immunocompromised as a result of the drug therapy and is susceptible to opportunistic infections and an increased incidence of cancer. One of the aims for the design of new immunosuppressive therapy is to develop protocols that are both effective and immunologically specific, such that only the immune response to the transplanted organ is suppressed. The optimal approach would be to induce tolerance to the donor histocompatibility antigens before transplantation, permanently paralysing the ability of the recipient's immune system to mount a rejection response against the graft. Some of the approaches for the induction of immunological tolerance currently being explored in clinical transplantation will be discussed. These include total lymphoid irradiation (TLI) and donor bone marrow transfusion combined with anti-lymphocyte globulin (ALG) post-transplantation. In addition some new approaches for the induction of tolerance before transplantation currently being investigated in experimental systems will be presented. PMID- 1916912 TI - Monitoring of rejection in renal transplantation. AB - With better immunosuppression, the results of kidney transplantation have improved greatly during the last 10 years. It has never been possible to completely suppress rejection, and transplant physicians and surgeons still need to maintain a constant vigilance in order that rejection does not go unrecognised in their patients. 1.1. CLINICAL FEATURES. These are often absent, although the patient may have noted a decreased urine volume and gain in weight. The kidney is sometimes tender and enlarged. 1.2. BIOCHEMICAL FEATURES. There is a rise in the plasma urea and creatinine and a reduced creatinine clearance. Unfortunately, other conditions such as cyclosporin nephrotoxicity can produce similar changes. 1.3. RADIOLOGICAL FEATURES. Isotope renography may demonstrate reduced renal perfusion and excretion but this is also seen in ATN. Ultrasound may demonstrate an increase in renal size. On Duplex renal ultrasonography changes in renal perfusion patterns can often be demonstrated. MRI has shown a loss of cortico medullary differentiation during rejection, but this is not very specific. 1.4. CYTOLOGICAL FEATURES. The presence of lymphocytes in the urine is often indicative of rejection, as is the finding of inflammatory cells in fine needle aspirates from the transplanted kidney. 1.5. HISTOLOGICAL FEATURES. Renal biopsies are best obtained using a Biopty Gun under ultrasound control. Cellular rejection is characterised by a heavy infiltrate of lymphocytes which invade the renal tubules (tubulitis). Vascular rejection is characterised by endothelial proliferation and fibrinoid necrosis of the vessel wall. 1.6. CONCLUSION. Several of the above tests are often required to establish the presence or absence of rejection. PMID- 1916913 TI - Immunophenotypic analysis of leukocyte infiltration in the renal transplant. AB - Immunohistological analyses of transplant biopsy material can provide valuable insight into the intragraft events following transplantation. The magnitude, composition and phenotype of the leukocyte infiltration and up-regulation of parenchymal antigen expression within the renal allograft have been major areas of interest. Immunohistological analyses have demonstrated the presence of leukocyte infiltration not only during clinical rejection episodes, but also during periods of stable graft function. Nevertheless the infiltration is significantly increased during clinical rejection. Indeed, quantitation of the leukocyte infiltration using a morphometric point counting technique or image analysis can be used prospectively to diagnose rejection in the renal transplant recipient. Macrophages and T lymphocytes (both of the CD4 and CD8 phenotype) are the major infiltrating cells, B lymphocytes and NK cells being present, but in the minority. Activated and proliferating cells have been demonstrated during allograft rejection and may provide a means of identifying a functionally active infiltrate. PMID- 1916914 TI - Fine-needle cytology in the monitoring of human renal allograft progress. AB - The differential diagnosis of early post-transplant renal dysfunction is complex. Clinical evaluation alone is often inaccurate and it is usually necessary to have recourse to additional investigation. Imaging methods, biochemistry and needle core biopsy have all proved invaluable in this way, but for making consecutive evaluations of renal allografts, fine-needle aspiration cytology has now emerged as a safe, rapid and reliable addition. Indeed, with a such a negligible incidence of complications, aspirates may be taken on a regular basis with the information obtained not only helping in routine diagnosis but also providing a useful research insight into the dynamic nature of the rejection process. The technique has evolved mainly over the past two decades, initially being based on traditional, semi-quantitative, morphometric cytology. However, monoclonal antibody technology and immunocytochemistry have been developing over the same time period and much use has been made of such procedures as immunofluorescence, immunoperoxidase, immunogold-silver and immunoalkaline phosphatase in further, more subtle analyses of aspirated cell populations. Renal aspiration cytology has become an established technology which is now being adapted to the study of liver, pancreas and even lung allografts. PMID- 1916915 TI - Techniques used to define human MHC antigens: serology. AB - The classical, routine test employed for definition of HLA antigens expressed in humans (tissue typing) is the complement-mediated cytotoxicity assay developed by Terasaki and McClelland in the early 1960s. In both healthy persons and patients, the assay target cells are usually lymphocytes obtained from peripheral blood, but when typing cadaver donors, splenic or lymph node lymphocytes can be used. HLA-A, B, Cw (class I) antigens are expressed on all nucleated cells while HLA DR, DQ (class II) are restricted to B lymphocytes and immune activated cells. Tissue typing has been achieved using culture cells from amniocentesis and typing of cell lines is possible with small modifications to the standardised cytotoxicity assay. Usually, target cells are incubated under oil with typing antisera at 22 degrees C in a 60- or 72-well Terasaki tray. After 30 min rabbit serum is added as a source of complement. After a further 60 min incubation the test is stained. A positive reaction results in target cell death. There are local variations to this test. Automation of the assay is now commonplace, from reagent dispensing to automated reading of finished assay. The use of antibody coated magnetisable microspheres has enabled separation of pure B lymphocyte samples for class II typing and has reduced incubation times through antigen modulation. It is possible to define antibodies to HLA antigens in the same assay using target cells with known HLA phenotypes. PMID- 1916916 TI - Pancreatic islet transplantation future prospects. AB - There is good evidence that the long-term complications of diabetes are caused by poor control of blood sugar, even in patients where intensive glucose monitoring is used to control insulin therapy. Pancreatic transplantation offers the potential for normalisation of glucose metabolism, but at the cost of major surgery and immunosuppression. The possibility of separating the insulin secreting tissue from the exocrine gland has many attractions. Isolated pancreatic islets are small enough to allow transplantation as free grafts by an injection technique. Furthermore, it may be possible to modify the graft in such a way as to prevent rejection with minimal or no immunosuppression. For pancreatic islet transplantation to become useful in clinical practice it will be necessary to develop efficient techniques for harvesting viable islet tissue in adequate quantities, identify a suitable site for transplantation and prevent rejection. Over the past 20 years experimental models of islet transplantation have proven the potential of this approach, but until recently it has not been possible to translate these experiments into clinical practice. Recently, there have been significant advances in the techniques available for separation of islets from the pancreas of large mammals and man, and recent clinical trials of islet transplantation have shown evidence of short-term function. However, significant problems remain, particularly those of rejection and the maintenance of long-term function, before introduction of clinical islet transplantation as standard therapy for diabetes can be expected. PMID- 1916918 TI - Epidermal allografts. AB - The epidermis is the sheet of stratified epithelial cells covering the dermal connective tissues. In addition to the epithelial cells (known as keratinocytes) there exist within the epidermis two populations of migratory leukocytes: the class II-positive, dendritic Langerhans' cell, and gamma-delta receptor-positive T lymphocytes. Allografts consisting essentially of epidermis have been in use since the introduction of "pinch" grafts by L. Reverdin in 1872. However, the capacity to culture keratinocytes in vitro to produce sheets of stratified epithelial cells has opened new possibilities. Cultured keratinocyte layers are devoid of passenger leukocytes and were initially widely believed not to be susceptible to rejection. This, however, is clearly not the case, at least in rats and humans. Nevertheless, in spite of severe acute rejection, it is interesting that cultured keratinocyte allografts are very poor at evoking antibody responses in graft recipients. Where permanent survival of the keratinocyte is required, autografts must be used, since the administration of immunosuppression to protect allografts would not be justified. Clinical application of cultured keratinocyte allografts, without immunosuppression, is limited to their use as temporary dressings (e.g., in burns) or to stimulate the recipient's own skin cells to growth (e.g., on leg ulcers). Autografts have been used for patients with extensive burns and in the treatment of chronic mastoiditis. PMID- 1916917 TI - Small bowel transplantation: future prospects. AB - The mesenteric lymph nodes and Peyer's patches of the small bowel present a significant target for immune attack in rejection. In addition they have the potential to proliferate and cause graft-versus-host disease (GVHD). Immune mediated impairment of mucosal barrier function will allow translocation of bacteria from the gut lumen into the blood stream. This factor, with the development of septicaemia, was probably responsible for the majority of deaths in early clinical cases treated with azathioprine and prednisolone. In the experimental situation GVHD and rejection can be studied as separate entities in transplants between parental strain rats and F1 hybrids. The use of immunohistochemical staining with strain specific monoclonal antibodies has enabled the migration pattern of lymphocytes to be studied. Within 24 h of transplantation donor lymphocytes can be detected in the spleen and mesenteric lymph nodes of the recipient. This cell transfer is clearly effected through the blood stream as the severed lymphatics of the grafted bowel take at least 7-10 days to regenerate and from connections with the recipient lymph system. At a practical level impairment of normal lymphatic drainage may cause problems with the absorption of fats and fat-soluble molecules such as cyclosporin. Denervation of the bowel also presents a problem in the initial phase after transplantation, with hypersecretion from the crypts causing diarrhoea. Since the introduction of cyclosporin a small number of successful human transplants have been reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916919 TI - Xenografts--future prospects for clinical transplantation. AB - This paper outlines the basic problems that still need to be overcome before xenografting becomes a reality. It presents evidence that if the first of these problems (preformed or natural antibody to pig) can be overcome then pig kidneys will: (a) not hyperacutely reject from a human; and (b) will not, under currently used immunosuppression, induce massive new primary or secondary responses. It also makes brief justification of the use of the pig as the donor of choice and outlines what essential animal work we feel necessary before an actual pig-to human transplant is contemplated. PMID- 1916920 TI - Techniques used to define human MHC antigens: monoclonals, class I and class II biochemistry. AB - A variety of straightforward biochemical techniques have been applied to the analysis of HLA molecules. These techniques centre largely on two components: monoclonal antibodies (mAbs) and gel analysis systems. Although only the basic applications are discussed here, the techniques have broad applications. Monoclonal-gel systems may be used for the characterisation of polymorphisms in HLA class I alpha chains or class II alpha and beta chains. This requires the use of mAbs which are locus-specific and monomorphic. Alternatively, B lymphoblastoid cell lines (B-LCL) whose HLA antigen mobilities are known in advance may be used for screening uncharacterised monoclonals for locus specificity. PMID- 1916921 TI - Regulation of MHC expression. AB - The level of expression of class I and class II MHC antigens in any particular cell is not a fixed characteristic, but is subject to wide fluctuation. The "resting" level of expression varies widely in different cell types, e.g., the cells of the exocrine pancreas and the myocardial cell express neither class I nor class II MHC antigens, whereas B lymphocytes express high levels of both class I and class II. The factors regulating these resting levels are beginning to be elucidated at the DNA level. The resting levels of class I and class II MHC antigen expression can be very greatly increased, primarily as a consequence of exposure to various cytokines released during inflammatory responses, but also in response to other non-specific stimuli. This probably represents an evolutionary adaptation to increase the capacity of infected tissues to present foreign peptides to the immune system, and thereby favour the survival of the host. However, when this phenomenon occurs in a transplanted organ, the increased expression of the now foreign MHC antigens in the context of the new host very likely plays a role in the graft's own destruction. The increased expression of class I MHC antigens, especially if the cell does not express these antigens at all at the time of grafting, will very likely render the cell susceptible to CD8+ cytotoxic T lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916922 TI - Techniques used to define human MHC antigens: polymerase chain reaction and oligonucleotide probes. AB - The various HLA class II specificities, identifiable by serological or cellular typing reagents, reflect underlying polymorphisms of the constituent alpha and beta chains, encoded at several loci within the HLA-D region. Variation in these genes is concentrated in allelic hypervariable regions but can also be found elsewhere. Sequence-specific oligonucleotides (SSO) can be used to detect individual alleles with a high degree of accuracy by probing dot-blotted DNA, amplified to high copy number by the polymerase chain reaction (PCR). The classic DR specificities (DR1-DRw14) can be identified with certainty by sequential hybridization to a series of 14 SSO probes. In addition, fine resolution of specificities such as the subtypes of DR4 is possible using a combination of SSO probes and group-specific amplification in which PCR primers designed to amplify only DR4 alleles are employed. Similar methods can be applied to the typing of DQ and DP alleles even on whole blood samples which have been stored at -20 degrees C for up to 8 years. A full HLA class II type may be obtained on a large number of samples simultaneously without the need to separate and store viable lymphocytes. Thus, the sensitivity and robustiness of this technique give it major applications in the analysis of histocompatibility and disease associations, particularly in circumstances where facilities for the initial preparation and storage of samples may be limited. PMID- 1916923 TI - The relationship between MHC restricted and allospecific T cell recognition. AB - The existence in the mature T cell repertoire of a high precursor frequency of cells which recognise allogeneic MHC molecules appears to contradict the well established dogma of positive selection for self MHC restriction. In order to explore the possibility that alloreactive cells are derived from a fraction of the repertoire that is not self-MHC-restricted, the contribution of in vivo primed T cells to "primary" alloresponses was investigated. Peripheral blood T cells were separated into virgin and memory populations by sorting for low and high levels of LFA-3 expression, and their proliferative responses to MHC incompatible stimulator cells was quantitated. The results demonstrated that approximately half of a "primary" alloresponse is contributed by previously primed T cells that, by definition, must be self-MHC restricted. Furthermore it was possible to define the original MHC-restricted antigen specificity of two T cell clones raised against the allospecific HLA-DR1 from a DR4Dw4/DRw13DW19 responder. The emerging consensus view that anti-MHC alloreactive T cells, like antigen-specific T cells, are specific for MHC/peptide complexes, and have a parental self-MHC restriction, begs a structural explanation. Comparison of multiple DR beta 1 domain sequences reveals that DR molecules fall into groups that have extensive homology in the residues on the beta 1 domain alpha-helix that are predicted to point up towards the T cell receptor (histotopic), and thus to determine MHC restriction. Given that the DR alpha chain is invariant this creates the possibility that anti-DR allorecognition can mimic self-restricted recognition. Within these groups of histotopically similar DR products there are multiple differences in the peptide-binding residues that lie on the inner aspects of the alpha-helix or on the floor of the antigen-binding groove. As a consequence, it is predicted that a different array of endogenous peptides will be bound, due to determinant selection. Thus, allorecognition within these groups may result from the recognition of endogenous peptides that are bound by stimulator but not by responder MHC products, seen in a self-restricted manner. In combinations where histotopic similarity does not exist, allorecognition may be best explained by the chance occurrence of a receptor selected for intermediate affinity for thymically expressed MHC molecules having a higher affinity for an allogeneic histotope. Such a receptor would have been deleted in a thymus expressing the allospecificity, but would be perceived as "safe" in the absence of this MHC product. PMID- 1916924 TI - Mechanisms of T lymphocyte activation. AB - The proliferation of T lymphocytes in response to an antigenic stimulus requires the successive ligation of a range of T lymphocyte receptors by MHC-presented antigen, molecules expressed on the surfaces of accessory cells and lymphokines. A range of intracellular signalling systems are involved, with the possibility of alternative activation pathways utilising different intracellular signalling systems, though protein kinase C activation appears to play a key role. Appreciation of the complexity of the response may allow more selective clinical modulation of T lymphocyte-dependent immunological responses. PMID- 1916925 TI - The role of HLA matching in transplantation. AB - All viable human tissues transplanted from one individual to another are at risk of rejection. The extent of risk depends on the donor HLA-host T cell receptor disparity. Such disparity is now known to involve genetic products coded by both HLA and non-HLA genes. T cell responses to mismatches on transplants are graded: the greater the mismatch the greater the number of clones of T cells responding. Consequently, the more severe the rejection process. Global statistics support this view in that cumulative mismatches at HLA are associated with poorer graft survival. However such studies also suggest that mismatches at different HLA loci vary in potency. The strength of mismatch seems to increase from HLA-A, the weakest, through HLA-B to HLA-DR, the most potent. Analysis of clinical results suggests that the risk associated with HLA mismatches in kidney transplantation dwindles after the first five months post-transplant. Although graft losses tend to occur sporadically thereafter, no major risk associated with HLA mismatches can be discerned. Whether this dwindling impact of HLA mismatches with time post transplant is a general phenomenon applicable to all transplants, or whether it suggests some form of adaptation of host to graft in kidney transplant recipients alone is a subject for further exploration. Tissues vary widely in their susceptibility to rejection through HLA mismatches.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916926 TI - Negative cross-match selection of HLA-DR compatible kidneys for highly sensitised patients. AB - Patients who have developed alloantibodies against almost all foreign HLA antigens are very difficult to transplant, because the cross-match with potential donors is often positive. The ideal donor for such patients is an HLA identical or compatible donor, but due to the enormous polymorphism of the HLA complex, the chance of finding such a donor is very small. The acceptable mismatch program, which takes advantage of the HLA-A and B antigens toward which the patient has not developed antibodies, and HLA-DR matching in the computerised selection of kidney donors, has significantly decreased the waiting time for these highly sensitised patients. Furthermore, graft survival is similar to that of non-highly sensitised patients. PMID- 1916927 TI - Immunological aspects of clinical renal transplantation. AB - Improved facilities for treating patients with end-stage renal failure have resulted in more elderly and debilitated patients being accepted for treatment. Renal transplantation is now the optimum form of treatment but organ procurement has failed to match clinical demand. Future developments may focus on further non specific immunosuppressive agents. As one year survival rates for first cadaver allografts now exceed 85% in many units, the significance of new developments will be increasingly difficult to evaluate. PMID- 1916928 TI - Immunological aspects of clinical liver transplantation. AB - With the improved survival achieved in the 1980s it has become apparent that graft rejection is a major problem following liver transplantation [1]. Hyperacute rejection is uncommon, although syndromes of fulminant graft failure due to immunological mechanisms have been described. Acute cellular rejection occurs in approximately 70% of patients and usually responds to high-dose steroids. Between 10 and 15% develop chronic rejection, characterised by a progressive destruction of intrahepatic bile ducts which is irreversible [2]. The principal targets of both acute and chronic liver allograft rejection are intrahepatic bile ducts and endothelium [2]. The increased ability of these cell types to express MHC antigens and adhesion molecules may be responsible for their involvement [2, 3] and may be enhanced by the release of proinflammatory cytokines associated with viral infection, particularly CMV [3]. Although the importance of HLA matching remains unknown patients transplanted with ABO incompatible livers have a higher incidence of graft rejection [4]. Lymphocytes probably instigate rejection but liver damage may result from the recruitment of several effector mechanisms involving the activation of neutrophils, macrophages and B cells as well as cytotoxic T cells [5]. Clinical studies are required to determine the optimum immunosuppressive management of liver transplants and in particular to assess the role of new immunosuppressive agents such as monoclonal antibodies and FK506. PMID- 1916929 TI - Immunological aspects of corneal graft rejection. AB - Immunological graft rejection is a major cause of corneal graft failure. HLA class I and II antigens are expressed by various cells within the cornea and during sensitisation of the recipient donor antigens appear to be presented by both donor and recipient antigen presenting cells. Certain donor and host factors have been shown to influence the incidence of corneal graft rejection, and the manipulation of these factors is discussed. PMID- 1916930 TI - Mechanisms of graft failure after human marrow transplantation: a review. AB - Graft failure (GF) following bone marrow transplantation (BMT) in man is usually attributed to allograft rejection; however, other mechanisms of GF exist. Exposure of the developing allograft to viruses, myelotoxic drugs, and damage to the host-derived marrow stroma during graft-versus-host disease (GVHD) may all cause GF. Later, in the posttransplant course, recurrence of the original disease may ultimately destroy or replace the graft. Overall allogeneic rejection remains the most important cause of GF and most in vivo and in vitro evidence points to a T cell mechanism. The incidence of rejection after clinical BMT is very variable and highly dependent on HLA and non HLA histocompatibility differences between donor and recipient, the level of recipient sensitisation pre-BMT and the immunosuppressive protocols used pre-transplant and for the prevention of GVHD. PMID- 1916931 TI - Immunosuppressive therapy in bone marrow transplantation. AB - Immunosuppressive and immunomodulatory techniques have a central role in bone marrow transplantation (BMT). A wide range of agents with different mechanisms of action, including steroids, cyclosporin, cytotoxic agents, irradiation and monoclonal antibodies are used to achieve the following treatment aims: (1) Suppression of the recipient's immunity to permit donor marrow engraftment and prevent graft rejection; (2) Prevention of graft versus host disease (GvHD); (3) Treatment of established acute or chronic GvHD. PMID- 1916932 TI - A critical review of immunosuppressive therapy. AB - Low-dose Prednisolone probably has a useful role in combination with other drugs, but is ineffective on its own in prophylaxis. Side effects are relatively mild in contrast to high-dose steroids. Azathioprine is a relatively non-toxic drug whose main side-effects are on the bone marrow and liver. As with steroids, it is ineffective on its own. Cyclosporin is undoubtedly the most potent of the currently available immunosuppressives. Careful monitoring is essential to avoid toxicity, in particular nephrotoxicity. Its value is enhanced by relative sparing of suppressor wells and B lymphocytes. While concern still exists regarding progressive long-term nephrotoxicity, it seems now more likely that this can be avoided by careful dose regulation. Hirsutism and cost are two important disadvantages. ALG, ATG and monoclonal antibodies directed against T lymphocytes (e.g., OKT3) or surface receptors such as IL-2 receptors are increasingly being used and there is hope of the development of an increasing range of new, more specific monoclonals. PMID- 1916933 TI - Minor histocompatibility antigens. AB - Immune responses against foreign tissue or organs can be directed against alloantigenic differences between donor and host encoded by genes of the major histocompatibility complex (MHC; HLA in man and H-2 in mouse). However, when MHC antigens are matched, as in HLA-identical siblings, or between different mouse strains sharing the same H-2 haplotype, graft rejection still occurs and is then directed against alloantigenic differences termed minor histocompatibility (H) antigens. Their molecular nature is not yet determined but they are recognised by T cells in an MHC-restricted manner, so are assumed to be derived from molecules co-expressed with MHC class I or II glycoproteins, possibly as peptides or as "super-antigens". The genes encoding them are scattered throughout the genome, including the Y chromosome, on which the H-Y antigen gene has been mapped in both man and mouse. One striking feature of minor H antigens is their recognition by T cells but not by antibodies. This made work with them, before our ability to generate T cell responses and maintain T cell clones in vitro, very slow but currently the use of MHC-restricted T cell clones has enabled detailed mapping studies and should eventually allow for their molecular characterisation. PMID- 1916934 TI - In vivo versus in vitro activity of cyclosporine. AB - Cyclosporine (CS) is a relatively new immunosuppressive agent which is selective in its action in that it acts on lymphocytes, T and B cells, and only indirectly if at all on other haemopoietic cells. Numerous studies over the last decade have shown quite clearly that, in vitro, CS inhibits lymphocyte activation at a relatively early stage by preventing the production and release of lymphokines, probably by inhibition of lymphokine gene transcription. However, studies in vivo have produced clearly different findings--although CS in vivo is completely effective in preventing the development of mature effector function (i.e., T dependent antibody synthesis by B cells or T cell-mediated cytotoxicity) and the consequences of that effector function (e.g., transplant rejection), there is clear evidence that lymphocytes can be activated to at least the stages of cell division and clonal expansion under cover of therapeutic levels of CS. The contradictions between in vitro and in vivo findings are discussed in terms of the possible mechanism of action of CS in vivo. PMID- 1916935 TI - Monitoring cyclosporin: is it still important? AB - This paper reviews the current data which provide a rationale for the measurement of cyclosporin as a guide to therapy. Methodological problems related to sample matrix and analytical technique are considered, and the most commonly used methods considered. Factors which could influence the clinical interpretation of cyclosporin measurements are examined, including other drug therapy, compliance with therapy, cyclosporin metabolites, pharmacokinetic variables and sample timing. It is concluded that, whilst isolated measurements do not offer a definitive diagnostic tool, taken in context they can be of considerable value in optimising therapy. PMID- 1916936 TI - Mutagenicity and carcinogenicity of tea, Camellia sinensis. AB - Aqueous, caffeine free and tannin fractions of commercial tea and tannic acid were tested for mutagenicity in Ames test. Tea fractions of tannic acid were non mutagenic in strains TA 100, TA 98, TA 1535 and TA 1538 of Salmonella typhimurium with or without metabolic activation (rat-S9 mix) at different doses tested. In strain TA 98 the above tea fractions and tannic acid inhibited the S9 mix mediated mutagenicity of tobacco in a dose dependent manner. The different tea fractions at 60 degrees C, did not increase the tumor incidence in Swiss mice by gavage feeding. They also failed to produce tumors when injected subcutaneously. Caffeine free tea extract decreased the tobacco induced liver tumors but had no effect on lung tumors. The same fraction was ineffective in hexachlorocyclohexane induced liver tumors in Swiss mice. PMID- 1916937 TI - Identification of DNA binding proteins which may regulate phosphoenolpyruvate carboxykinase gene. AB - Transcription of phosphoenolpyruvate carboxykinase (PEPCK) gene is induced in response to cyclic AMP (cAMP) or cAMP elevating hormones. The role of transcription factors (DNA binding proteins) in the induction process has been studied. Two nuclear proteins, apparent mol. wt of 53 and 30 kDa, have been shown to bind to the 5'-flanking DNA of PEPCK gene which contains hormonal responsive elements as well as TATA box. DNA binding activity of 53 kDa protein increases by 3.5 fold in cells treated with 8-(4-chlorophenylthio)-cAMP (8-CPT-cAMP). The increased binding activity may be due to the phosphorylation of this protein by an activated cAMP-dependent protein kinase (cA kinase) in treated cells. Based on this observation, a hypothesis that 53 kDa may be specific transcription factor for PEPCK and therefore, play a major role in the regulation of this gene is proposed. PMID- 1916938 TI - Identification of immune complex antigens in sera of Indian kala-azar patients. AB - Level of circulating immune complex (IC) in visceral leishmaniasis is much higher than that in control sera. In immunoblot experiment, treatment of kala-azar IC with patient sera showed at least 6 bands of which the band around 55 kDa region was most prominent. The band at 55 kDa is primarily due to the presence of an antigen recognized by its corresponding antibody present in the patient sera. This was confirmed by using radiolabelled antibody from kala-azar patient serum and antipromastigote serum. The heavy chain of IgG originating from IC is also present in the same region which was detected by its recognition with antihuman IgG. The IC gave a band at 55 kDa region with sea-urchin antitubulin. Kala-azar sera also reacted with purified rat brain tubulin. The present results suggest that a tubulin like protein is present at 55 kDa region along with the heavy chain of IgG. PMID- 1916939 TI - Identification and size variation of terminal fragments of sheep pox virus genome. AB - Terminal fragments of sheep pox virus DNA identified by snap-back analysis showed terminal covalent cross-links. Southern blot hybridization using a terminal fragment probe confirmed the termini and terminal repeats (common sequences) of the sheep pox virus genome. Terminal fragment length variability was observed between virus isolates. PMID- 1916940 TI - Potential application of dot-immunobinding assay as a rapid diagnostic test in tuberculous meningitis. AB - A simple dot-immunobinding assay (Dot-Iba) in nitrocellulose paper was developed for the detection of specific IgG antibody to Mycobacterium tuberculosis antigen 5 and mycobacterial antigen in cerebrospinal fluid of patients with tuberculous meningitis (TBM). The assay gave 77.1% sensitivity for the detection of IgG antibody to M. tuberculosis antigen 5 and 48.6% sensitivity for the detection of mycobacterial antigen in patients with TBM. PMID- 1916941 TI - An enzymeimmunoassay method for thyroxine determination in serum samples. AB - Here we describe an enzymeimmunoassay (EIA) for thyroxine (T4) in serum, whose performance is comparable to that of a sensitive T4 radioimmunoassay (RIA). In this assay, specific T4 antibody adsorbed on polystyrene beads is used along with T4-horseradishperoxidase as the tracer and omicron-phenylenediamine as chromogen. Several samples were analysed both by this T4 EIA and by using a commercial RIA kit for T4. The results correlate well with a correlation coefficient r = 0.9 and slope = 0.93 (n = 50). PMID- 1916942 TI - Rapid serodiagnostic test for pulmonary tuberculosis. AB - Immune complexes (ICs) were isolated from sera of patients with pulmonary tuberculosis (PT), non-tuberculous pulmonary diseases and healthy control subjects by polyethylene glycol (PEG) precipitation method. Specific mycobacterial antibody in ICs was tested against an affinity purified mycobacterial antigen by counter-current immunoelectrophoresis (CIE). The results show that specific mycobacterial antibodies are present only in ICs of patients with PT (70%). Therefore CIE could be used as a simple and rapid serodiagnostic test in patients with PT, particularly when bacteriological methods in sputum specimens are negative for Mycobacterium tuberculosis. CIE has several operational advantages over ELISA and best suited to laboratories with limited resources. PMID- 1916943 TI - Glutathione and glutathione-related enzymes in busulfan treated rat lens. AB - Glutathione (GSH) and GSH-related enzymes, glutathione reductase (GR), gamma glutamyl cysteine synthetase (gamma-GCS), gamma-glutamyl transpeptidase (gamma GTP), glutathione S-transferase (GST) and adenosine triphosphatase (ATPase) enzymes were analysed to study the effect of busulfan on the defence mechanisms of the lens. All these enzymes were found to increase significantly except GSH which showed only 7.9% increase as compared to controls in precataractous stage. These results affirm that busulfan is capable of evoking a response from the enzymes involved in the various pathways of GSH enabling the lens to prolong its clarity. The cataractous lenses showed significant decrease in all these parameters. Here, the impairment of the defense mechanism (GST, GR) and the total ATPase may be attributed to the cumulative action of the drug which can react with -SH groups of these enzymes, ultimately causing opacification. PMID- 1916944 TI - Lethal and haemorrhagic activity of Russell's Viper venom--neutralization by polyvalent, monovalent and toxoid antiserum. AB - Lethal and haemorrhagic activity of Russell's Viper venom was compared against polyvalent bivalent commercial antiserum and monovalent antiserum raised in rabbit. Formaldehyde-detoxified venom offered 7-fold protection against lethal activity and 12.5-fold against haemorrhagic activity of the venom. Whole venom and formaldehyde-detoxified venom along with Freund's complete adjuvant, injected in rabbits produced high titre antiserum. Amongst all the six antiserum tested, the monovalent antiserum raised in rabbit, showed maximum precipitating bands in immunogeldiffusion and immunoelectrophoresis. The toxoid-antiserum offered maximum protection against the venom-induced lethality and the monovalent antiserum offered maximum protection against haemorrhagic activity. PMID- 1916945 TI - Changes in macrophage membrane proteins in relation to protein deficiency in rats. AB - Resident and thioglycollate (TG) macrophages were isolated from rats fed 20 and 4% protein diets. These cells were cultured for 2 and 18 hr; further the membrane proteins were separated by SDSPAGE. Though basically all the samples had a similar banding pattern, the protein profile was very complex in nature. TG elicited macrophages from the protein fed group had increased contents of high molecular weight proteins compared to the resident cells from both the groups as well as TG cells from the protein deficient group. The difference increased with prolonged incubation. Polypeptides at 56.5 and 46 kd which were prominently present in the control samples, was very low in the protein deficient ones. Bands at 34, 32, 27 to 19.5 kd were reduced in the TG cells from the protein fed group. The protein deficient samples exhibited a strong band at 43 kd (presumably actin) while it was present in very small amounts in the cells from the protein fed groups. These observations indicate that the protein restriction had down regulated TG induced modulation of macrophage membrane proteins to the level of resident cells which are physiologically in a lower state of activation. These changes could reflect on their reduced functional properties. PMID- 1916946 TI - Effects of protein restriction on functional properties of rat peritoneal macrophages. AB - Rats were maintained on 20% and 4% protein diets for 3 weeks. The functional properties of thioglycollate (TG) elicited macrophages from these groups were compared with the non elicited resident cells from the protein fed group. Elicitation of macrophages in response to TG was low in the protein deficient group. These cells also exhibited low adherence in overnight cultures compared to those isolated from the protein fed group; however their viability and total protein content remained unaltered. Normal resident and TG elicited cells from 4% protein fed group exhibited an initial lag period in H2O2 production in response to zymosan stimulation. The lag period could be correlated to the high endogeneous catalase activity in these cells. Incubation with zymosan resulted in rapid decline in catalase levels, facilitating evolution of H2O2. On prolonged incubation, the elicited cells from the protein fasted rats evolved about 87% H2O2 compared to the protein fed samples. In the absence of zymosan all the samples possessed comparable NADPH oxidase activity. Zymosan induced activation of this enzyme was higher in TG cells from the protein fed groups, compared to the protein fasted and the resident samples. The cellular enzyme activity, however was not altered in the TG cells of both the groups though it declined rapidly in the corresponding resident cells. Significant reduction (congruent to 50%) in both serum iron and transferrin in the low protein fed samples did not correspondingly affect the oxidative burst process. However the engulfment of yeast cells was greatly impaired due to protein restriction. Adherence and phagocytic properties of macrophages are regulated by the activity of their membrane constituents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916947 TI - Effect of calcium channel blocker (diltiazem) on platelet aggregation. AB - Platelet aggregation with collagen, ADP and sodium arachidonate was significantly inhibited by 0.48 and 0.24 mg/ml of diltiazem but no significant effect occurred with 0.024 mg/ml of diltiazem. It is suggested that the antiplatelet property of diltiazem may be utilized in clinical setting and diltiazem may be tried synergistically with other antiplatelet drugs. PMID- 1916948 TI - Antioxidant protection mechanism of chick hepatic mitochondria exposed to lanthanum chloride & neodymium chloride treatment. AB - Acute lanthanum chloride (250 mg/kg body wt) and neodymium chloride (200 mg/kg body wt) administrations resulted in significant enhancement of glutathione level in chick hepatic mitochondria. However, glutathione-s-transferase activity was depressed. There was no alteration in the activity of glutathione reductase. Activity of glucose-6-phosphate dehydrogenase was not altered under lanthanum and neodymium treatment. There was a significant enhancement of intramitochondrial glutathione peroxidase and superoxide dismutase. Lipid peroxidation remains the same as control group of animals. PMID- 1916949 TI - Essential components of mitochondrial protein import apparatus in Saccharomyces cerevisiae. PMID- 1916950 TI - Evaluation of in vitro cytotoxic T lymphocyte assays as a predictive test for the occurrence of graft vs host disease. AB - The potential value of in vitro cytotoxic T lymphocyte (CTL) assays for predicting the occurrence of graft vs host disease (GVHD) following allogeneic bone marrow transplantation was evaluated in 12 mouse donor-host combinations associated with various degrees of GVHD. These donor-host combinations were selected after evaluation of GVHD triggered by minor histocompatibility antigens (MiHA) in 24 allogeneic strain combinations derived from six strains of H-2b mice. Recipients (n = 475), previously submitted to total body irradiation (9.5 Gy), were transplanted with 10(7) bone marrow cells along with 5 x 10(7) spleen cells. While lethal GVHD was observed in half of the strain combinations, it was possible to select 12 donor-host combinations characterized by severe, mild, or absent GVHD. When levels of anti-host CTL activity were assessed following in vivo priming and in vitro boosting, strong CTL-mediated cytotoxicity was observed in all combinations whether they developed GVHD or not. CTL frequency measured by limiting dilution analysis (LDA) ranged from 1/16880-1/306. The Spearman rank test revealed no positive correlation between GVHD intensity and donor anti-host CTL activity assayed either in bulk culture experiments or in LDA conditions. These results indicate that MiHA capable of triggering potent CTL responses in vitro do not necessarily initiate GVHD, and that in vitro measurement of donor CTL activity against host-type Con A blasts is not a predictive assay for anti MiHA GVHD. However, the possibility to recruit CTL populations targeting host MiHA expressed specifically on hematopoietic cells suggests a novel therapeutic strategy for the cure of hematopoietic malignancies. Indeed, transplantation of donor hematopoietic stem cells supplemented with T cells aimed at MiHA specifically expressed by host hematopoietic cells, could possibly potentiate the desirable graft vs leukemia effect without increasing the risk of GVHD. PMID- 1916951 TI - Polymorphism in V kappa 10 genes encoding L chains of antibodies bearing the Ars A and A48 cross-reactive idiotypes. AB - p-azophenylarsonate-specific antibodies of A/J mice which bear the Ars-A crossreactive idiotype utilize the V kappa-Ars-A gene segment, a member of the V kappa 10 family. Southern hybridization of genomic DNA from several inbred strains using a probe from the 5' flanking region of the V kappa-Ars-A gene demonstrated three patterns of restriction fragment length polymorphisms (RFLP). Six genes corresponding to hybridizing bands were obtained from DNA libraries of C.AKR, PERU and A/J mice, and nucleotide sequence comparisons revealed two allelic groups: AKR1 (Igk-V10.1a), AJ1 (Igk-V10.1b) and PERU1 (Igk-V10.1c); AKR2 (Igk-V10.2a), AJ2 (Igk-V10.2b), and PERU2 (Igk-V10.2c). The Igk-V10.1b gene of the A/J strain is the V kappa-Ars-A gene used in Ars-A idiotype-positive antibodies. The product of the C.AKR allele (Igk-V10.1a) contained four amino acid substitutions in CDR3 as compared with Igk-V10.1b. These substitutions probably explain the failure of AKR mice and other strains with the same V kappa 10 RFLP pattern to provide in genetic crosses a L chain which, together with the A/J VH-ArsA gene product, form Ars-A idiotype-positive antibodies. Also, the nucleotide sequence identity between the Igk-V10.1c and Igk-V10.1b alleles and the Igk-V10.2c and Igk-V10.2b alleles is significantly greater than that seen in comparisons with the Igk-V10.1a and Igk-V10.2a alleles, respectively, suggesting an evolutionary pathway similar to that of the linked Igk-J locus. BALB/c antibodies bearing the A48 regulatory idiotype contain L chains encoded by the BALB/c Igk-V10.1b and Igk-V10.2b alleles. Strongly A48 idiotype-positive antibodies utilize the Igk-V10.1b chain, and weakly A48-positive antibodies use the Igk-V10.2b L chain. The possible effects of amino acid substitutions specified by the Igk-V10.1a, Igk-V10.1c, Igk-V10.2a, and Igk-V10.2c alleles on their ability to provide L chains used in A48 idiotype-positive antibodies are discussed. PMID- 1916952 TI - Allelic differences in hemolytic activity and protein concentration of BF molecules are found in association with particular HLA haplotypes. AB - After separating the *F and *S alleles by electrophoresis the allele-specific hemolytic activity was detected by agarose overlay method using the programmable densitometer for scanning. The hemolytic activity of BF allotypes was analyzed from 81 individuals. In thirteen FS heterozygous serum samples BF F had lower hemolysis than BF S. Four FF homozygous samples also exhibited lower hemolysis than a homozygous control sample. The low hemolytic activity of F in FS heterozygotes was not due to decreased protein concentrations relative to S. On the contrary, BF F was associated with higher protein concentration than BF S. The relative quantitation of the allele specific BF protein was done by crossed immunoelectrophoresis. BF F with low hemolytic activity but with high protein concentration associated strongly with HLA B35 phenotype and the family material confirmed the association with the haplotypes A3, Cw4, B35, DR1, BFFB, C4A3BQO (or A2BQO, A3,2BQO). The results suggest that particular MHC haplotypes contain a factor B allele with encoding for poor hemolytic activity or that MHC haplotype specific regulatory elements affect pre- or post-translational activity levels. PMID- 1916953 TI - Transfected human class I gene product adequately assembles minor histocompatibility antigens. PMID- 1916954 TI - An intragenic recombinant class I gene: H-2Ddx. PMID- 1916955 TI - Kayser-Fleischer like ring in autoimmune chronic active hepatitis. AB - Kayser-Fleischer ring is considered an important diagnostic sign of Wilson's disease. We report a 9 year old boy with autoimmune chronic active hepatitis who exhibited Kayser-Fleischer like ring. PMID- 1916956 TI - Intestinal malrotation in adults. AB - Intestinal malrotation presenting with abdominal problems are not common beyond the neonatal period. An adolescent or adult harboring this anomaly may suffer from delay in diagnosis and inappropriate treatment including surgery. We report three patients, aged 17, 31 and 50 years, with intestinal malrotation presenting as an appendicular problem (2) and chronic abdominal pain (1). The former mode of presentation has not been reported so far. PMID- 1916957 TI - Retained surgical sponge simulating colonic carcinoma. PMID- 1916959 TI - Amebic pericarditis following ruptured right liver lobe abscess. AB - We present an unusual case of suppurative pericarditis following rupture of a solitary right lobe amebic liver abscess. The condition was treated successfully by drainage of the liver abscess alone. PMID- 1916961 TI - Delta infection in acute hepatic failure. PMID- 1916960 TI - Frequency and pattern of gastrointestinal tumors in Kashmir. PMID- 1916958 TI - Primary malignant melanoma of esophagus. AB - Primary esophageal melanoma is a rare tumor. A 35 year old male with primary malignant melanoma of the esophagus is reported. He presented with dysphagia and weight loss. At autopsy a fusiform polypoidal growth was seen in the middle third of the esophagus. Microscopic sections showed a malignant melanoma in an in situ as well as invasive form. PMID- 1916962 TI - Domperidone induced galactorrhea. PMID- 1916963 TI - Indigenous PEG tubes: further modifications. PMID- 1916964 TI - Percutaneous pancreatography in tropical pancreatitis. PMID- 1916965 TI - 2nd annual conference, UP State Chapter, Indian Society of Gastroenterology; King George's Medical College, Lucknow; March 8-9, 1991. PMID- 1916966 TI - Diagnostic scoring systems: have they arrived? PMID- 1916967 TI - A scoring system to differentiate cirrhotic from non-cirrhotic portal hypertension. AB - When it is not possible to perform a liver biopsy in cirrhosis, one has to rely on suggestive clinical and biochemical parameters and imaging procedures to arrive at a presumptive diagnosis. Based on the statistical method described by Spiegelhalter and Knill-Jones, we have devised a scoring system to reliably differentiate cirrhotic from non-cirrhotic portal hypertension without a liver biopsy. Age, presence of ascites, liver scan result and serum albumin, taken together, could confirm or rule out the diagnosis of cirrhosis in two-thirds of patients with portal hypertension. A score of 5 or more suggested cirrhosis (sensitivity 78%), and of 5 or more suggested cirrhosis (sensitivity 78%), and a score of -6 or less suggested a non-cirrhotic cause (sensitivity 64%) for portal hypertension, both with 100% specificity. Eliminating liver scan result reduced both sensitivity and specificity, suggesting that liver scan is an important component of the score. This score may be useful not only in the management of individual patients but also to classify them in clinical trials. PMID- 1916968 TI - Separate pancreatic and biliary ductal openings in alcoholic chronic pancreatitis. AB - Endoscopic retrograde cholangiopancreatograms of 49 patients with chronic pancreatitis (alcohol related 18; idiopathic 31) were assessed retrospectively. Thirteen (72%) of 18 patients with alcohol-related chronic pancreatitis had separate openings of the common bile duct and the main pancreatic duct into the duodenum. This was significantly more frequent (p less than 0.01) than in previously studied controls (37%). Although this finding was seen more frequently in patients with alcohol related chronic pancreatitis than in those with idiopathic chronic pancreatitis (14 of 31, 45%), the difference was not statistically significant. It is concluded that alcohol-related chronic pancreatitis, but not idiopathic chronic pancreatitis, is associated with the presence of separate openings of the common bile duct and main pancreatic duct into the duodenum. PMID- 1916969 TI - Extraintestinal manifestations of idiopathic ulcerative colitis. AB - One hundred and fifty patients of idiopathic ulcerative colitis were studied for extraintestinal manifestations by clinical, radiological and biochemical means. One or more such manifestations occurred in 34.7% of patients. Sacroiliitis (14%) and peripheral arthritis (10.7%) were the commonest manifestations, followed by ocular (8%), mucocutaneous (2.7%), vascular (2%) and hepatobiliary (1.3%) manifestations. We conclude that the incidence and spectrum of extraintestinal manifestations in Indian patients with idiopathic ulcerative colitis are similar to those in western patients. PMID- 1916970 TI - Ribavirin in acute viral hepatitis. AB - A double-blind, placebo-controlled trial using ribavirin (200 mg orally four times a day for two weeks) was conducted in 30 patients with acute uncomplicated viral hepatitis (excluding hepatitis B). Clinical and laboratory parameters were evaluated on days 5, 10 and 14 after starting treatment. Mean levels of ALT and AST were significantly lower in the ribavirin treated group as compared to the placebo group on days 5, 10 and 14; serum bilirubin levels were significantly lower in the ribavirin group on days 10 and 14. Ribavirin therapy was not associated with any significant side effects. We conclude that ribavirin therapy in acute uncomplicated non-B viral hepatitis leads to more rapid normalisation of biochemical parameters. PMID- 1916971 TI - Hepatitis E: the enterically transmitted non-A, non-B hepatitis. PMID- 1916972 TI - Esophagitis: clinical and endoscopic assessment of sucralfate therapy. AB - Twenty patients with endoscopically proved reflux esophagitis were studied. Each patient was given 1 gm sucralfate 4 times a day for 6 weeks. Clinical and endoscopic assessment of the effects of sucralfate on reflux esophagitis was done. 50% patients became asymptomatic and 60% healed endoscopically. The drug was well tolerated. We conclude that sucralfate is an effective and well tolerated drug for treatment of reflux esophagitis. PMID- 1916974 TI - Nosocomial infection due to salmonella senftenberg (case report). AB - Besides various clinical manifestations and made of spread of Salmonella infections, isolation of S. senftenberg a rare serotype from patients hospitalised for surgical procedures indicates nosocomial infection. A prolonged stay in hospital with surgical trauma facilitated the organism to cause infection in the compromised host. PMID- 1916973 TI - Role of radiotherapy in the management of primary carcinoma of the fallopian tube. AB - Primary fallopian tube carcinoma is a rare neoplasm. It may be postulated that postoperative loco-regional radiotherapy is a valuable adjunctive in the overall management of the tubal carcinoma. However, we can't advocate the efficacy of this approach authentically due to a very small number of cases. A prospective controlled and randomized trial with larger patient number may yield some definite conclusions regarding it's optimal management. PMID- 1916975 TI - Retinal detachment surgery. PMID- 1916977 TI - Lactate dehydrogenase (LDH) isoenzymes patterns in ocular tumours. AB - Estimation of lactate dehydrogenase (LDH) isoenzymes in the serum and aqueous humor was carried out in 15 cases of benign ocular tumour, 15 cases of malignant tumor and 15 normal cases. Cases of both sexes aged between 1 year and 75 years were included. LDH, isoenzymes specially LDH4 and LDH5 are higher and LDH1 and LDH2 lower in sera of patients with malignant tumor specially retinoblastoma as compared to benign tumor cases and control cases. LDH isoenzymes in aqueous humor are significantly higher and show a characteristic pattern in retinoblastoma cases, the concentration was presumably too low in the control, malignant tumor other than retinoblastoma and benign tumor cases as its fractionation was not possible. PMID- 1916976 TI - Scleral buckling with hydrogel implant. AB - The hydrogel implant for scleral buckling, first developed in 1980, is said to combine the advantages of both solid silicone rubber and silicone sponges. But it is still not widely used. Our clinical experience with the hydrogel implant used in 23 cases of rhegmatogenous retinal detachment is described. It was used both as exoplant and implant. Anatomical success was achieved in 91% of the cases. There was no infection, erosion, migration of extrusion of the buckle. The advantages are that it is soft, elastic, nontoxic, and nonpyogenic; it is devoid of infection and postoperatively it swells up, for additional heightening of the buckle. This new material appears to combine the advantages of both silicone sponge and solid silicon rubber thereby providing an ideal buckling material. PMID- 1916979 TI - Prediction of intra ocular lens power in 100 patients using the ophthasonic a scan unit. AB - The aim of this study was to determine the range of ametropias encountered by using the computerized Ophthasonic A-Scan. The SRK formula was used to compute the IOL power using axial length and keratometry as inputs. The accuracy of prediction of IOL power was calculated by noting the disparity between the expected post-operative refraction and the actual refraction obtained after one and a half months of IOL implantation. The results obtained were encouraging; the maximum deviation from the expected result being +/- 3.2 D. PMID- 1916978 TI - One point low volume peribulbar anaesthesia versus retrobulbar anaesthesia. A prospective clinical trial. AB - A prospective trial was conducted on 142 patients who underwent cataract surgery, to compare the efficacy of a single point, low volume peribulbar with that of retrobulbar anaesthesia. It was found that peribulbar anaesthesia is as efficacious as retrobulbar anaesthesia without the associated complications. It also avoids the facial block used by most ophthalmologists to supplement a retrobulbar block, thus markedly reducing the post-operative patient discomfort as well as the total volume of anaesthetic used. PMID- 1916980 TI - Why go endocapsular? AB - A prospective randomized clinical trial was carried out to compare the intercapsular or the endocapsular technique of IOL insertion and conventional posterior chamber IOL insertion after can opener capsulotomy. Age and sex matched groups of 76 patients each underwent surgery by the two techniques. The corneal and the uveal reaction was evaluated on the first day after the surgery and specular counts were done at six weeks. Though the difference between the two groups was not statistically significant, a trend in favour of intercapsular technique emerged strongly. PMID- 1916981 TI - Hospital epidemiology of dry eye. AB - One hundred consecutive cases of dry eye were studied to comment upon its epidemiological aspects. The incidence of dry eye amongst ophthalmic outpatients was 0.46% with a male:female ratio of 1:1.22. Fifty seven percent of the patients were above 50 years of age. The incidence was higher amongst outdoor workers and people from rural areas with poor socioeconomic status. The influence of hot and dry climate and nutritional status on dry eye incidence is discussed. PMID- 1916982 TI - Conjunctival microbial flora in leprosy. AB - Conjunctival sacs of seventy one leprosy patients, paramedical and medical personnel working in a leprosy home were cultured. None of these eyes had any pathology in the outer eye. Surprisingly, 46.2% of the eyes which showed a positive culture carried accepted pathogens; Staphylococcus aureus being the commonest. Determining the preoperative bacterial flora and their elimination before undertaking intraocular surgery is recommended. PMID- 1916983 TI - Visual evoked response in macular diseases. AB - Visual evoked responses (VER) were recorded in 10 patients with unilateral maculopathy. VER latency and amplitude were compared between the affected and unaffected eyes. Evaluation of results reveals that in macular disease with fluid accumulation (Central Serous Retinopathy and Traumatic Macular Oedema) the VER showed amplitude reduction depending on reduced visual acuity with no significant change in latency, whereas, in disease with degeneration of retinal layers, (Degenerative Maculopathy) latency was markedly increased signifying associated conduction defect. PMID- 1916984 TI - Congenital nystagmus with head posture (a modified approach in surgical management). AB - The surgical methods for correction of an abnormal head posture in congenital nystagmus presently in use, do not correct the head posture adequately and in some cases produce a postoperative tropia. We felt that this may be related to the arbitrary quantities of surgery suggested by various workers. We have observed that surgery on the medial rectus is approximately one and a half times as effective as on the lateral. Using this ratio, excellent results have been obtained in 5 cases which are reported herein. PMID- 1916985 TI - Self-inflicted corneal injuries in a child with congenital sensory neuropathy (a case report). PMID- 1916986 TI - Malignant melanoma of choroid. AB - Four cases of malignant melanoma of the choroid are reported due to rarity of the condition in India. One of the cases presented with Naevus of Ota. All the cases had typical clinical and investigative features. All cases were enucleated. Histopathologically three of them were of mixed type and one was of the epithelioid type. Two of the cases were seen in patients below 40 years of age. PMID- 1916987 TI - Groenblad Strandberg syndrome--a case report. AB - A rare case of Groenblad Strandberg syndrome in which angioid streaks are associated with pseudoxanthoma elasticum is being reported. The pathology, clinical features, complications and treatment of angioid streaks are discussed in detail. PMID- 1916988 TI - Cavernous hemangioma of the frontal bone: a case report. PMID- 1916989 TI - Irvine H. Page: 1901-1991. The celebration of a leader. PMID- 1916991 TI - Cyclosporine causes sympathetically mediated elevations in arterial pressure in rats. AB - Cyclosporine-induced immunosuppression has emerged as a new cause of hypertension, but the underlying mechanisms are poorly understood. In patients, this hypertension is accompanied by sympathetic neural activation. We therefore hypothesized that increased sympathetic nerve discharge is an important mechanism by which cyclosporine raises blood pressure. To test this hypothesis, we examined effects of acute administration of cyclosporine (5 mg/kg i.v.) or vehicle on renal and lumbar sympathetic nerve activity, renal and femoral blood flow velocity (pulsed Doppler flowmetry), and arterial pressure in chloralose anesthetized rats. Vehicle had no effect on sympathetic nerve activity, whereas cyclosporine caused renal and lumbar sympathetic nerve activity to increase progressively over 60 minutes to levels that were 362 +/- 46% and 388 +/- 70%, respectively, of the baseline values (p less than 0.05). These increases in sympathetic nerve activity were accompanied by proportional increases in renal and femoral vascular resistance and sustained increases in mean arterial pressure (+19 +/- 3 mm Hg, p less than 0.05 versus baseline). The cyclosporine-induced increases in regional vascular resistance and arterial pressure were greatly attenuated, or abolished, by ganglionic blockade or by clonidine (central sympatholysis) but were unaffected by angiotensin converting enzyme inhibition. These findings demonstrate that in an anesthetized animal preparation, the vasoconstrictor and blood pressure-raising effects of cyclosporine are caused by sympathetic neural activation. PMID- 1916990 TI - Structure, expression, and regulation of the murine renin genes. AB - It has long been known that the renin-angiotensin system plays an integral role in the regulation of blood pressure and electrolyte and fluid balance in mammals. The advent of molecular biologic techniques has afforded new insights into the genes regulating blood pressure. Laboratory mice and rats have been used as experimental models to examine the structural organization and expression of the renin gene. It is now well established that some mice, unlike rats and humans, contain a duplicated copy of the renin locus, which accounts for the high level of renin activity long known to be found in the submandibular gland of some mice. Indeed it is this fortuitous observation that facilitated the isolation of the first complementary DNA clones for renin and ultimately the many species-specific probes now available to analyze mammalian tissues for evidence of primary renin expression. The use of complementary DNAs as probes for primary renin expression helped confirm and further clarify earlier studies demonstrating the presence of renin activity in a number of extrarenal tissues. Although expression in some of these tissues is evolutionarily conserved, their significance has still been elusive. In this report we review the impact of molecular biology on our current understanding of renin gene structure and organization, tissue- and cell-specific expression and regulation, and the changes in renin expression throughout ontogeny. In addition, we describe how new developments in gene transfer technology have added important tools to our arsenal for examining renin gene regulation and how these technologies can be used to develop new tools for renin and hypertension research. PMID- 1916992 TI - Pathogenesis of hypertension in the sinoaortic-denervated spontaneously hypertensive rat. AB - The present study was performed to examine the relation between the gain of the baroreceptor reflex and the pathogenesis of hypertension in the spontaneously hypertensive rat. Spontaneously hypertensive or Wistar-Kyoto rats underwent either sinoaortic baroreceptor denervation or sham denervation at 28-35 days of age. Four months later these rats were chronically instrumented for measurements of arterial pressure and heart rate. Sixty-minute computerized measurements of arterial pressure showed no difference between spontaneously hypertensive sham (163 +/- 5 mm Hg) and spontaneously hypertensive baroreceptor-denervated (166 +/- 5 mm Hg) rats, or Wistar-Kyoto sham (114 +/- 3 mm Hg) and Wistar-Kyoto baroreceptor-denervated (121 +/- 4 mm Hg) rats. The gain of baroreceptor reflex control of heart rate was assessed by measuring maximal heart rate responses to changes in arterial pressure elicited by bolus injection of phenylephrine and nitroprusside (gain = slope of linear regression equation of change in heart rate versus change in arterial pressure). Baroreceptor reflex gain was significantly higher in Wistar-Kyoto sham rats (-2.10 beats/min/mm Hg) than spontaneously hypertensive sham rats (-0.94 beats/min/mm Hg). Baroreceptor denervation significantly decreased baroreceptor reflex gain in both Wistar-Kyoto (-0.26 mm Hg) and spontaneously hypertensive (-0.22 beats/min/mm Hg) groups. Since baroreceptor denervation did not exacerbate the development of hypertension in adult spontaneously hypertensive rats or lead to hypertension in Wistar-Kyoto rats, we conclude that a primary dysfunction in the baroreceptor reflex alone is not responsible for the development of hypertension in this model. PMID- 1916993 TI - Sympathoadrenal control by paraventricular hypothalamic beta-endorphin in hypertension. AB - The paraventricular hypothalamus regulates autonomic nerve outflow and is innervated with beta-endorphin-immunoreactive nerve terminals. This study examined the effects of beta-endorphin microinjected into the paraventricular hypothalamus on blood pressure, heart rate, and plasma catecholamine and glucose concentrations in conscious, unrestrained spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at the age of about 9 weeks. Thirty minutes after paraventricular hypothalamic injection of [125I] beta-endorphin (3.5 micrograms), most of the recovered radioactivity was detectable within +/- 0.5 mm from the injection site in the coronal, sagittal, and horizontal planes. Unilateral paraventricular hypothalamic injections of beta-endorphin (1 and 0.1 microgram/0.1 microliter) increased blood pressure and heart rate in both strains in a dose-independent manner with significantly greater increases in SHR. Plasma catecholamine and glucose concentrations were measured 15, 30, and 60 minutes after beta-endorphin injection. Norepinephrine concentrations were not significantly altered in WKY rats but increased in SHR. Epinephrine concentrations increased in both strains with significantly greater increases in SHR. Increases in catecholamine concentrations were not dose-related. Glucose concentrations also increased in both strains with significantly greater increases in SHR only at the lower dose. Ganglionic blockade with pentolinium significantly reduced beta-endorphin-induced pressor and tachycardiac responses in SHR. Pretreatment of the paraventricular hypothalamus with naltrexone (1.1 micrograms) in SHR blocked the initial pressor and tachycardiac responses to beta endorphin (0.1 microgram) and blunted increases in epinephrine and glucose levels. When the animals were anesthetized with alpha-chloralose 2-5 days after the study in conscious animals, there were no differences in blood pressure or heart rate between strains after beta-endorphin (0.1 microgram) injection. The results indicate that conscious SHR show enhanced cardiovascular and sympathoadrenal responses to beta-endorphin injected into the paraventricular hypothalamus, suggesting that alterations in the activity of the paraventricular hypothalamic beta-endorphin system can modulate the development of hypertension in SHR. PMID- 1916994 TI - Endothelin in hypertensive resistance arteries. Intraluminal and extraluminal dysfunction. AB - The effects of intraluminal and extraluminal endothelin-1 and its interactions with endothelium-derived relaxing factor were studied in perfused mesenteric resistance arteries of Wistar-Kyoto rats and spontaneously hypertensive rats. Changes in intraluminal diameter were recorded. In adult Wistar-Kyoto rats, but not spontaneously hypertensive rats, low concentrations of intraluminal endothelin-1 (10(-10) to 10(-9) M) caused relaxations of quiescent arteries blocked by indomethacin. After endothelial removal, intraluminal endothelin-1 evoked concentration-dependent contractions in both strains. Extraluminal endothelin-1 caused greater contractions of arteries with endothelium than intraluminal endothelin-1, and the sensitivity was lower in adult hypertensive rats; endothelial removal enhanced the contractions to extraluminal endothelin-1 to a greater extent in hypertensive than in normotensive rats. In arteries without endothelium, intraluminal and extraluminal endothelin-1 caused comparable contractions, but the sensitivity was reduced in adult but not young hypertensive as compared with normotensive rats. Both young spontaneously hypertensive and normotensive rats exhibited a high sensitivity to the peptide. In arteries precontracted with endothelin-1, endothelium-dependent relaxation to intraluminal acetylcholine was reduced in hypertensive as compared with normotensive rats, whereas relaxations to extraluminal acetylcholine were increased in hypertensive rats. Thus, endothelin-1 interacts with both vascular smooth muscle and the endothelium. The sensitivity of vascular smooth muscle to endothelin-1 is reduced in adult hypertensive rats. Intraluminal activation of the endothelium by endothelin-1 or acetylcholine is reduced in spontaneously hypertensive rats, whereas extraluminal activation causes more pronounced responses in hypertensive than in normotensive rats, suggesting a prominent dysfunction of the intraluminal surface of the endothelium in hypertension. PMID- 1916995 TI - The renin-angiotensin system and the vascular wall from experimental models to man. A symposium. Monte Carlo, October 12-13, 1990. PMID- 1916997 TI - Cardiac and aortic effects of angiotensin converting enzyme inhibitors. AB - The effects of six angiotensin converting enzyme inhibitors (captopril, CGS 16617, cilazapril, enalapril, utibapril, and quinapril) on cardiovascular structure, systemic hemodynamics, left ventricular end-diastolic pressure, left ventricular pumping ability, and aortic distensibility were assessed in male normotensive Wistar-Kyoto and spontaneously hypertensive rats 16-19 weeks of age. Rats (10 in each group) were treated for 3 weeks with drugs or control diluents administered daily by gavage. The agents, in general, had similar hemodynamic effects, although these effects on cardiac mass were variable; some agents reduced left ventricular mass and some produced no change. These effects occurred in hypertrophied as well as nonhypertrophied chambers. Furthermore, changes in left ventricular pumping ability were not necessarily related to the ability of these agents to change left ventricular mass; this dissociation in performance was neither related to change in structure nor to changes in aortic distensibility. Thus, even within a same class of antihypertensive agents (i.e., angiotensin converting enzyme inhibitors), similarly induced hemodynamic alterations were associated with inconsistent changes in left ventricular pumping ability or aortic distensibility regardless of whether the structure was hypertrophied before therapy. These dissociated responses in cardiovascular structure and function may be related to pharmacodynamic or pharmacokinetic differences; alternatively, they also may be related to these differences in action on local myocytic renin-angiotensin systems or in intramyocytic biological responses. PMID- 1916996 TI - Molecular mechanisms of vascular renin-angiotensin system in myointimal hyperplasia. AB - Angiotensin II has been shown by many investigators to be a potent growth factor for vascular smooth cells in culture as well as in vivo. Depending on the conditions, the response of these cells is either hypertrophy or hyperplasia. These observations have important clinical implications, because it has been shown that angiotensin II participates in the hypertrophic response of the vessel wall during hypertension and the hyperplastic response after balloon angioplasty. Thus, an understanding of the molecular mechanism of these responses is important in the development of potential treatment strategies. This review examines the evidence for the growth-promoting properties of angiotensin II, concentrating on these molecular mechanisms. Hypotheses are presented that may explain the bifunctional effects (hypertrophy versus hyperplasia) of angiotensin II. These hypotheses revolve around the interaction of angiotensin with endothelium- and smooth muscle cell-derived products. These autocrine and paracrine interactions play important roles in the modulation of vascular structure. PMID- 1916999 TI - Effects of saralasin on arterial compliance in normotensive and hypertensive rats. Role of endothelium. AB - We used an experimental model of in situ isolated carotid arteries to clarify the participation of angiotensin II (Ang II) in the mechanical properties of the arterial wall in 12-week-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). The effects of local incubation with saralasin ([Sar1,Thr8]Ang II, 10(-6) M) on carotid compliance were compared with the effects of endothelium removal and with those of total abolition of vasomotor tone with potassium cyanide (0.1 mg/ml). Operating carotid compliance measured for pressure values close to the mean arterial pressure of each group was (mean +/- SD) 12.6 +/- 2.9 x 10(-3) microliters/mm Hg.mm vessel in WKY rats and 8.2 +/- 1.6 x 10(-3) microliters/mm Hg.mm vessel in SHRs (p less than 0.001). With intact endothelium, local incubation with saralasin increased carotid compliance by 24% in WKY rats and 23% in SHRs relative to control values (p less than 0.05 and p less than 0.001, respectively). Endothelium removal induced significant increases in carotid compliance in WKY rats (17%, p less than 0.01) and in SHRs (33%, p less than 0.001). After endothelium removal, saralasin induced significant further carotid compliance increases in both strains (+18%, p less than 0.001, and +11%, p less than 0.01, in WKY rats and SHRs, respectively). After potassium cyanide poisoning, carotid compliance did not increase further relative to saralasin values in both strains with or without endothelium. These findings suggest that Ang II receptors play a major role in the control of the basal vasomotor tone of large arteries in both normotensive and hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1916998 TI - Effects of the converting enzyme inhibitor cilazaprilat on endothelium-dependent responses. AB - The effects of cilazaprilat were assessed on endothelium-dependent relaxations and contractions in isolated canine arteries. In coronary arteries incubated with indomethacin, cilazaprilat potentiated endothelium-dependent relaxations to bradykinin. In superfusion-perfusion bioassay studies with femoral arteries, cilazaprilat augmented the release of nonprostanoid endothelium-derived relaxing factors caused by bradykinin. To verify whether this effect was solely due to inhibition of the converting enzyme, the effects of cilazaprilat on responses to a variety of endothelium-dependent vasoactive agents were assessed. Endothelium dependent relaxations to acetylcholine, thrombin, and vasopressin were not altered significantly by cilazaprilat. However, those induced by ADP and aggregating platelets were enhanced significantly by the compound. Endothelium dependent relaxations to ADP-beta-S were augmented significantly but to a lesser extent. Furthermore, in the presence of the nitric oxide synthase antagonist NG nitro-L-arginine, ADP-beta-S still caused small relaxations that were possibly mediated by endothelium-derived hyperpolarizing factor. These relaxations were augmented by cilazaprilat. Thus, the augmentation of purinergic relaxations may involve an increased production of endothelium-derived relaxing factors in addition to the protection of ADP from breakdown. Cilazaprilat did not affect endothelium-dependent contractions to acetylcholine or the calcium ionophore A23187 in canine basilar arteries, previously shown to be mediated by superoxide anions. Thus, cilazaprilat is not a scavenger of superoxide anion. Because this agent potentiates endothelium-dependent relaxations to bradykinin, ADP, and aggregating platelets, the present study suggests that, in addition to the lowering of plasmatic levels of angiotensin II, the antihypertensive and cardioprotective effects of cilazaprilat are mediated through an increased production of endothelium-derived relaxing factors. PMID- 1917000 TI - Effect of converting enzyme inhibition on allograft-induced arterial wall injury and response. AB - Converting enzyme inhibition (CEI) can prevent myointimal proliferation after arterial wall balloon injury. Because intimal proliferation is the main long-term complication of chronic vascular rejection, we tested the effect of CEI (perindopril, 1 mg/kg twice a day) on arterial rejection-induced intimal proliferation, using a model of aortic allograft in normotensive Wistar-Kyoto and spontaneously hypertensive rats. Eight-week-old rats were grafted and studied 2 months later. The structural parameters of the transplanted aortic wall were measured by morphometric analysis of specifically stained, formol-fixed sections. CEI did not prevent adventitial inflammatory infiltration but significantly increased the number of living cells and prevented the partial destruction of elastic laminae in the media, thereby increasing medial thickness to close to that of sham-operated controls. CEI significantly decreased intimal thickness and intimal collagen density, without changing the absolute number of intimal smooth muscle cells. The intimal thickness and the intimal collagen density were significantly correlated with the effect of CEI on blood pressure. CEI partially prevented the consequences of immune injury to the media within the arterial wall, probably by suppressing the proinflammatory activity of angiotensin II. It also decreased the recipient arterial wall response by acting more on the trophicity of intimal cells and on their ability to produce collagen rather than by directly inhibiting smooth muscle cell proliferation in our model of arterial allograft. PMID- 1917001 TI - Endothelial function in humans. Studies of forearm resistance vessels. AB - The endothelium is increasingly recognized as a modulator of vascular tone, and evidence also is accumulating for an important role of the endothelium in humans in vivo. Endothelial release of prostacylin appears to regulate hyperemic blood flow after ischemia and muscle exercise, and the potent vasodilating properties of endothelium-derived relaxing factor (EDRF) are well established. Tonic release of EDRF plays an important role in the regulation of vascular tone in normal subjects, and a reduction of EDRF release in response to muscarinergic stimulation has been described in subjects with uncomplicated hypertension and also in hyperlipidemic patients. These observations point toward an early disturbance of endothelial function in disorders known as risk factors for the development of atherosclerosis. Furthermore, altered EDRF release and responsiveness to stimuli may be involved in the disturbed regulation of peripheral vascular tone in congestive heart failure. The physiological role of the vasoconstricting peptide endothelin-1 is not yet defined, but the study of the vascular actions of the peptide in humans has shown a vasodilating effect (for low dosages or when the vasconstricting effects are blocked), as well as a marked and long-lasting vasoconstricting effect. Although the mechanisms leading to vasodilation are not clear in humans, endothelin-1-induced vasoconstriction appears to be completely dependent on the activity of voltage-operated calcium channels and can be blocked by organic calcium antagonists but not by nitrovasodilators or EDRF. Further clarification of the role of the endothelium will provide a better understanding of circulatory physiology and pathophysiology and eventually may lead to the development of new therapeutic modalities. PMID- 1917002 TI - Endothelial function in human coronary arteries in vivo. Focus on hypercholesterolemia. AB - To examine whether and to what extent hypercholesterolemia may affect the vasoactive role of the endothelium before the onset of angiographically visible atherosclerosis in the coronary circulation, we studied normal subjects (group 1, n = 11), individuals with elevated low density lipoprotein plasma values but angiographically smooth coronary arteries (group 2, n = 8), and patients with hypercholesterolemia and minimal disease of the vessel under study (group 3, n = 8). Coronary vasomotor function was evaluated by three interventions: subselective intracoronary infusion of acetylcholine (0.036, 0.36, and 3.6 micrograms/min) with a 3F Doppler catheter in the left anterior descending artery, 0.3 mg intracoronary nitroglycerin ("endothelium-independent"), and increase in blood flow (assessment of flow-dependent, endothelium-mediated coronary dilation). In group 1, all interventions caused coronary dilation of the left anterior descending artery as assessed by automatic quantification of digitized cineframes. However, in group 2, acetylcholine elicited substantial coronary vasoconstriction, and the vasodilator response to nitroglycerin and to increases in flow (flow-dependent dilation) was preserved. In group 3, the acetylcholine-induced coronary vasoconstriction was even more pronounced, and the flow-dependent dilation was impaired (+5.1 +/- 1% versus +10.5 +/- 1.1% [group 1], p less than 0.05). The coronary flow reserve (derived from Doppler flow velocity measurements) in response to papaverine was not significantly different in normal and hypercholesterolemic individuals (groups 2 and 3). However, the increase in coronary flow exerted by acetylcholine was substantially depressed in patients with hypercholesterolemia (groups 2 and 3) as compared with normal individuals (+48 +/- 8.3% and +49 +/- 25% versus +220 +/- 28.5%, respectively, p less than 0.01). Thus, hypercholesterolemia elicits endothelial dysfunction in coronary conduit and resistance vessels in humans that precedes angiographically visible atherosclerotic lesions in large coronary arteries. Conceivably, these vascular alterations contribute to increased coronary vasomotor tone within the coronary circulation and may predispose these patients to myocardial ischemia. PMID- 1917003 TI - The heart to heart stuff. PMID- 1917004 TI - Hypolipidaemic and antiatherosclerotic effects of plumbagin in rabbits. AB - Plumbagin (2-methyl-5-hydroxy, 1:4 naphthoquinone) isolated from the roots of Plumbago zeylanica when administered to hyperlipidaemic rabbits, reduced serum cholesterol and LDL-Chol. by 53 to 86 percent and 61 to 91 percent respectively. It lowered cholesterol/phospholipid ratio by 45.8 percent and elevates the decreased HDL-Chol significantly. Further, Plumbagin treatment prevented the accumulation of cholesterol and triglycerides in liver and aorta and regressed atheromatous plaques of thoracic and abdominal aorta. Plumbagin treated hyperlipidaemic subjects excreted more fecal cholesterol and phospholipids. In conclusion-Plumbagin feeding brings about a definite regression of atheroma and prevents the accumulation of cholesterol and triglycerides in liver and aorta. PMID- 1917005 TI - Lung function development in Indian men and women during late adolescence and early adulthood--a longitudinal study. AB - Lung function development was studied in a cohort of Indian men (n = 31) and women (n = 36), over a period of four years during late adolescence and early adulthood. Forced expiratory spirograms and peak expiratory flow rates were recorded at intervals of approximately two years. All volumes and flow rates were higher in men, but volume adjusted flow rates were higher in women. Forced vital capacity (FVC) forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) were significantly higher in men even after standardizing for age, height and weight. Height and PEF increased significantly in men and women over the four years. Volumes showed a greater increase whereas flow rates and volume adjusted flow rates showed a greater decrease in men. The decline in the forced expiratory flow in the middle half of the FVC (FEF 25-75%) was significantly less in women. These results suggest that although lung size is greater in men, small airway dynamics may be better in young women. PMID- 1917006 TI - A comparative study of lung functions in rice mill and saw mill workers. AB - A lung function study was carried out to determine the relative effect of rice husk and saw dust on mill workers. The study consisted of 195 subjects of which 56 rice mill workers, 71 saw mill workers and 68 controls of similar age, sex and socio-economic condition. FVC was significantly reduced in saw-mill workers compared to both the controls and rice mill workers. Both FEV1 and PEFR/min were significantly reduced in both mill workers compared to controls. The fall in PEFR/min in saw mill workers was also significant when compared to rice mill workers. FVC was reduced after 5 years of exposure only in saw mill workers. FEV1 was reduced within a year which was further reduced after 5 years in both mill workers. PEFR/min was highly reduced within a year remained so even after 5 years. PMID- 1917007 TI - Learning, memory and the brain. AB - Human and non-human animals acquire information about the world through the process of learning, and store that information as memory. Yet central as the storage process is to adaptive behaviour, progress in understanding its neural bases has been slow and only recently efforts have shown clear signs of being successful. The knowledge that comes from this progress strongly suggests that different kinds of learning involve different neural circuits and accordingly involve different memory systems. Indeed, it is becoming increasingly clear that multiple memory systems may be a fundamental part of the design of the vertebrate brain. It has long been supposed that learning leads to the formation, or to the strengthening of particular pathways in the brain. Once formed, or strengthened in this way a pathway was viewed as a 'trace' or 'engram' 'representing' the particular experience or relationship which had been learned. There is substantial evidence that neural pathways, especially synaptic connectivity, can be modified by experience-as by rearing rats in an 'enriched' environment with other rats rather than rearing them in isolation--as well as by modifying the diet or by depriving young rats of their thyroid gland. This evidence demonstrates that the central nervous system is plastic, but provides no hint that such plasticity is involved in learning. The evidence that synaptic plasticity is indeed involved in learning and memory is relatively recent. PMID- 1917008 TI - Ethanol induced electroencephalographic changes from certain central loci of canine brain. AB - Effect of intracerebroventricular (i.c.v.) ethanol on pre-optic area (POA) and hippocampus (HPC) was investigated by recording chronological changes in their electroencephalographic (EEG) activity, through chronically implanted cannulae and bipolar electrodes, in five conscious male beagle dogs. Recordings were made for two hours after microinjection and compared with cortical (CO) tracings. The predominant pattern of EEG activity from subcortical loci was high voltage discharges though synchronization was also observed. Cortical EEG depicted slow waves with some potentiation. The study demonstrated similar type of response form POA and HPC, which was different from CO, suggesting that ethanol produces different actions at subcortical and cortical level. PMID- 1917009 TI - To assess effect of noise on hearing ability of bus drivers by audiometry. AB - The present study was planned to assess the noise levels to which the drivers from State Transport Sangli Depot., are exposed during their duty hours and to explore the effects of high intensity noise of their hearing ability by audiometric examination. The study was done both in study and control group. Noise levels were measured in the driver's cabin and in the working place of the controls which ranged from 89 to 106 dB and 50 to 62 dB respectively. Audiometric examinations were performed in the study and control groups. 89% of the drivers and 19% from the control group showed abnormal audiograms. PMID- 1917010 TI - Peak expiratory flow rates in elderly Indians. AB - Peak expiratory flow rates were measured in 124 normal elderly men (55-85 yr) using the Wright's peak flow meter. In the less than 60 yrs age group (n = 32; mean age 57.7 yr) the PEFR was 431 +/- 13 lpm, while for the group greater than 60 yr (mean age 69.0 +/- 6.0; n = 92), the PEFR value was 373 +/- 11 1pm. These values are similar to those reported in other Indian studies, suggesting that the ethnic variations amongst Indian subjects do not affect the PEFR. However, the reported values are lower than those observed in Europeans, but greater than those of Chinese. The PEFR regressed at a rate of 4.47 1pm/year increase in age, but is positively correlated to the subjects' height (cm), and their FVC and FEVI. The smokers had a significantly higher PEFR as compared with the non smokers. This finding was contrary to what was expected. PMID- 1917011 TI - Longitudinal study of lung function development in a cohort of Indian medical students: interaction of respiratory allergy and smoking. AB - This study was done to identify some factors that affect the growth and development of lung function during adolescence and early adulthood. Forced expiratory spirograms and peak expiratory flow rates were obtained in a cohort of normal young men (n = 63) over a period of 4 years, at intervals of approximately 2 years. Two factors that disturbed the normal pattern of lung function development in this group were smoking and respiratory allergy. Among the smokers and the allergics the decline in the forced expiratory volume expressed as a percentage of the forced vital capacity (FEV1%), the forced expiratory flow in the middle half of the forced vital capacity (FEF25-75%) and the FEF25-75% expressed as a ratio of the forced vital capacity (FEF/FVC) was more than double that among the normal subjects. The number of smokers and of allergics increased during the course of the study from 15 to 19 and from 16 to 23 respectively. There was a significant (P less than .01) interaction between smoking and the manifestation of respiratory allergy. Among nonsmokers, the number of allergic subjects increased from 12 to 13, while among smokers it increased from 4 to 10, during the four years. PMID- 1917012 TI - A membrane-free plethysmograph for recording volume changes including microlitres. AB - A method of plethysmography which does not require an air/water tight chamber is described. The method is sensitive enough to record microlitre volumes/volume changes. Its application in two situations, viz. in experimental (artificial) edema and blood flow measurement in the human hand has been demonstrated. PMID- 1917013 TI - Circadian rhythmicity of growth hormone at high altitude in man. AB - Circulatory levels of growth hormone (GH) were estimated at 0600 h, 1200 h, 1800 h and 2400 h in each of 10 subjects of sea level residents (SLR) in New Delhi (226 m) and in high altitude natives (HAN) settled at an altitude of 3650 m. Both in SLR and HAN the GH secretion showed an identical pattern, the values were lowest at 0600 h and highest at 2400 h. Nevertheless, in HAN the GH levels at different timings of the day were found to be significantly higher than in SLR. PMID- 1917014 TI - Variations in plasma trace-elements concentration during fracture healing in dogs. AB - The study was conducted on healthy Mongrel dogs. Fracture of Radius Ulna was inflicted with wire-saw. Subsequently repair was carried out using bone plates. Plasma Zinc concentrations decreased significantly from control values of 317.71 to 294.92 micrograms/dl at day one post-operatively and the values reached basal levels by 21st day. The concentrations of plasma Copper, Cobalt and Iron continued to decrease during the post-operative period. However, Manganese concentration increased significantly during the corresponding post operative period. Results indicate withdrawal of minerals from body reserves during bone repair. PMID- 1917015 TI - Effect of mid-dorsal caudate nucleus on conditioning for pain stimulus in rats. AB - Male rats were subjected to conditioning, with light source as conditioned stimulus, followed by a noxious stimulus applied to the tail as unconditioned stimulus. There was development of conditioned response after a few days, which was inhibited later on. PMID- 1917016 TI - Baroreceptor reflexes in postural control of circulation in rabbits. AB - The present study was undertaken to evaluate reflex cardiovascular responses to postural stress in rabbits. The changes in mean arterial pressure (MAP) and heart rate (HR) were monitored in the supine position and following sudden passive head up tilt (HUT), and head down tilt (HDT) to 70 degrees. The results show a significant increase in MAP (18.57%, P less than 0.001) and HR (2.92%, P less than 0.02) with HUT; and a marked decrease in MAP (43.48%, P less than 0.001) and HR (8.21%, P less than 0.001) with HDT (as compared to the values in supine position). The changes in MAP were found to be more marked than those in HR. The depressor responses to HDT were more marked than the pressor responses to HUT. PMID- 1917017 TI - Study of serum immunoglobulins in normal pregnancy. AB - Suppression of maternal immune response may be one of the factors contributing to continuation of pregnancy, a state in which the foetus exists as a well tolerated homograft. Studies on serum immunoglobulin levels in pregnancy show varying results. In this study serum immunoglobulin levels of Ig G, Ig A and Ig M were estimated in 75 normal pregnant women, 25 in each trimester. These were compared with a control group of 25 healthy women. A graded significant decrease in Ig G levels was observed throughout the pregnancy. Ig A levels decreased during the first and second trimester of pregnancy. A significant increase in Ig M levels from the first to third trimester was observed. PMID- 1917018 TI - Role of acetylcholine and dopamine in dorsal hippocampus on hoarding behavior in rats. AB - The probable roles of Acetylcholine (Ach) and Dopamine (DA) in the modulation of instinctual behaviors of feeding and hoarding (HS), as also the body weight and vaginal cyclicity (EI), were studied by instillation of Atropine (Ach antagonist), Haloperidol (DA antagonist) and Apomorphine (DA agonist) in the dorsal hippocampus of nonpregnant female rats. It was observed that the HS was significantly decreased with both Atropine and haloperidol and increased with Apomorphine, although the food intake was decreased with the three chemicals. It appears that action of both Ach and DA on the dorsal hippocampus has a positive influence on hoarding behavior. PMID- 1917019 TI - Expiratory flow rate changes during the menstrual cycle. PMID- 1917021 TI - Mucosal immunology I: Basic principles. PMID- 1917020 TI - Ontogeny of the mucosal immune system and IgA deficiency. AB - Studies of ontogenesis contribute to better understanding of regulatory events underlying the striking heterogeneity in B-cell differentiation pathways employed in the human mucosal immune system. This disparity is probably explained by exogenous environmental factors, although regional differences probably also exist in accessory cells and cytokines involved in local immune responses. IgA deficiency signifies a heterogeneous syndrome but is basically a manifestation of a defect in B-cell differentiation. The immaturity of the IgA system revealed in this disorder bears a striking resemblance to that seen in newborn infants. It may therefore be worthwhile to consider IgA deficiency in relation to the ontogeny of mucosal immunity. PMID- 1917022 TI - Selective transport of IgA. Cellular and molecular aspects. AB - The principal characteristic immunoglobulin of mucosal surfaces, secretory immunoglobulin A (S-IgA), is the product of two different types of cell present in mucosal and glandular tissues. Submucosal plasma cells, which are generated largely within the common mucosal immune system, synthesize predominantly polymeric, J chain-containing IgA, which is selectively bound by polymeric immunoglobulin receptor or secretory component (SC) on the basolateral surfaces of mucosal and glandular epithelial cells. The molecular and cellular events involved in SC expression, its intravesicular transport together with its polymeric IgA ligand to the apical surface of the epithelial cell, during which IgA becomes covalently linked to SC, and the proteolytic cleavage of SC from the apical membrane to release S-IgA into the lumen have been elucidated. Additional receptors and mechanisms for the uptake, catabolism, and transport of IgA exist, especially in the liver. The biologic significance of IgA transport lies in the secretion of large quantities of S-IgA antibodies for the protection of huge areas of mucosal surfaces and for the provision of passive immunity to suckling infants, and in the immune elimination of antigenic materials by hepatobiliary transport. PMID- 1917023 TI - The regulation of IgA B-cell differentiation. AB - IgA B-cell differentiation is affected by several kinds of events. One key event, IgA B-cell switch differentiation, is a process that may be controlled by tissue specific "switch" cells or an identifiable switching cytokine or lymphokine that operates in an IgA-specific fashion. Another event, or group of events is IgA B cell terminal differentiation in B cells already switched to IgA. Such terminal differentiation may also be regulated in an IgA-specific fashion, at least insofar as class-nonspecific lymphokines can be presented to IgA B cells in a class-specific fashion by cells bearing IgA-Fc receptors. Emerging knowledge of the regulation of IgA B cells offers many opportunities to enhance or inhibit IgA B-cell development at several levels. In coming years this will prove important, not only in devising ways of protecting against mucosal pathogens, but also in modifying immunologic diseases that have their basis in mucosal immune system dysfunction. PMID- 1917024 TI - Regulation of lymphocyte traffic to mucosa-associated lymphatic tissues. AB - Lymphocyte recognition and binding to endothelial cells at sites where lymphocytes exit the blood is controlled by several molecules. At mucosal sites, the lymphocytes use at least VLA-4, CD44, and LFA-1 (CD18/CD11a) to bind the endothelial cell ligand molecules. The endothelial cell surface ligand for CD44 is probably a human equivalent of MECA-367 and hyaluronate. LFA-1 can bind to ICAM-1/ICAM-2; and VLA-4, to VCAM-1 on endothelium. However, for physiologic lymphocyte migration, these molecules may still need additional ligands that are currently uncharacterized. At sites of inflammation, cytokines increase the expression of ICAM-1, VCAM-1, and a third endothelial cell antigen, ELAM-1, whose counter-receptor on leukocyte surface is presently unknown. Upregulation of these molecules apparently facilitates the traffic of lymphocytes and other leukocytes to sites of inflammation, thus partially determining the nature and extent of inflammation. These same molecules may be equally responsible for the pathologic characteristics of the immune response seen, for example, in inflammatory bowel diseases. PMID- 1917025 TI - Structure and function of intestinal M cells. AB - M cells are structurally distinctive, uniquely permeable epithelial cells found only overlying the domes of mucosal lymphoid follicles. Antigenic macromolecules and some viruses, bacteria, and protozoa enter their apical surface by endocytosis or phagocytosis. These substances traverse the M-cell cytoplasm by transcytosis, breaching the epithelial barrier, and then interact with the subepithelial immunocompetent cells to initiate mucosal and systemic immune responses. The M cell serves as a portal of entry for selected pathogens that cause disease locally in the wall of the intestine or, following dissemination, at distant sites. The mechanisms that regulate adherence to and penetration of M cells by macromolecules and microorganisms are not known, but selective binding of secretory IgA to the luminal surface may be important. Whether M cells simply serve a sieving function and always transport substances unchanged across the epithelial barrier or whether they also sort and process antigens they endocytose and present them to adjacent lymphoid cells requires further study. PMID- 1917026 TI - Intestinal intraepithelial lymphocytes. AB - Recent data on phenotype, differentiation, and functions of intestinal intraepithelial lymphocytes (IEL) in rodents and in humans are reviewed in this article. IEL form a large population of activated T cells located at the interface between the body and the septic intestinal content. Phenotypic studies indicate that IEL are mainly CD8-positive cells that contain both TCR alpha beta and TCR gamma delta cells in variable proportion depending on the species and antigenic intraluminal stimulation. Studies in experimental models suggest a dual origin, both thymus-dependent and thymus-independent of IEL, and a role of the gut epithelium in the differentiation of IEL. Functional studies allow insight on the mechanisms by which IEL can protect the intestinal epithelium or conversely, when abnormally activated, induce epithelial damage. PMID- 1917027 TI - Antigen handling by the epithelium and lamina propria macrophages. AB - The absorptive enterocyte of the small intestine expresses MHC class II antigens both constitutively and as a result of induction by cytokines. This can function to restrict antigen presentation in vitro. However, there is no direct evidence that its function in vivo is to restrict the presentation of absorbed soluble protein antigens to the available intraepithelial lymphocyte population. Alternatively, the class II molecule may be acting as a receptor for immunologically relevant antigen and transporting this antigen in a protected route across the epithelium. A third possibility concerns a possible educational role for epithelial class II. The epithelium of the intestine is identical in embryologic origin to thymic epithelium, which is known to be involved in the positive selection of alpha/beta TCR CD4-positive and CD8-positive T cells. The early development in ontogeny of epithelial and lamina propria cells expressing class II, the association of gamma/delta TCR with IEL (at least in rodents), and the reported thymus independence of these gamma/delta IEL26 all support speculation that the Ia-positive cells of the lamina propria in the fetus and the epithelium in the adult cooperate to restrict the diversity of the response to bacterial antigens and, in the antigen-free fetal state, to self-antigens. A mechanism providing constant positive selection or tolerization of T cells responsive to bacterial or food antigens would be very beneficial. The macrophage/dendritic lineage cells of the lamina propria can present antigen and modulate the response to that antigen. Because the subpopulations of these cells in the lamina propria are distinct from the antigen-handling cells of Peyer's patches, however, it is likely that the follicular and diffuse lymphoid tissues have evolved either to respond to different types of antigen or to induce and regulate different responses to the same antigen. PMID- 1917028 TI - Gastrointestinal mast cells. New approaches for analyzing their function in vivo. AB - Mast cells have been implicated in a variety of physiologic or pathologic responses in the gastrointestinal tract; however, the precise contributions of the mast cell to these reactions have been difficult to define. This article discusses general aspects of mast cell biology, outlines new approaches for the analysis of mast cell function in vivo, and reviews recent evidence indicating that mast cells can produce a wide spectrum of multifunctional cytokines. PMID- 1917030 TI - Screening for Chlamydia trachomatis in military personnel by urine testing. AB - In order to determine the infection rate of Chlamydia trachomatis in young males in Austria an epidemiological study was performed on 335 male Austrian soldiers attending the military hospital for a health check-up procedure. Three hundred twenty-nine (98.2%) of the screened males were clinically asymptomatic. Chlamydial diagnosis was established by testing first catch urine (FCU). Urine sediment was tested by an enzyme immunosorbent assay (EIA) and by a direct immunofluorescent test (DIF test). Positive results in both tests were defined "true positives." In 41 (12.2%) of all the 335 soldiers a genital chlamydial infection could be demonstrated by a positive result of the sediment of the FCU in both tests. 93% of the positive results in the DIF test could be confirmed by the EIA whereas only 77% of the positive EIA tests were also positive in the DIF test. Data on genital symptoms and the history of sexually transmitted diseases (STDs) as well as information about sexual relationships were available from all persons included in the study and did not differ between chlamydia positive and negative ones. The study demonstrates a high infection rate with C. trachomatis in mostly asymptomatic young males when using FCU for chlamydial diagnosis. Due to the discrepancy between the EIA and the DIF test, positive results of the sediment of FCU in the EIA test should be confirmed by the DIF test to eliminate false positive cases. PMID- 1917029 TI - Corynebacterium jeikeium bacteremia at a tertiary care center. AB - During a six-year period 23 patients with isolation of Corynebacterium jeikeium (formerly known as Corynebacterium group JK) from one or more blood cultures at a university hospital were identified. Cases occurred sporadically without time- or ward-related clustering. Review of the cases showed that most infections were nosocomial, that most of the patients had underlying malignant disease, had a chronic intravascular catheter implanted, had been pretreated with antibiotics, and were neutropenic at the time the blood cultures were drawn. Patients with only one versus those with more than one positive blood culture differed in some important aspects. Patients with only one positive blood culture were less likely to have acute leukemia, had significantly higher neutrophil counts and a shorter duration of preceding antibiotic treatment, and all had other probable causes of infection and fever. The mortality also appeared to be lower in these patients. Despite the possibility of increasing frequency of blood cultures positive for C. jeikeium, severe infections due to this organism continue to be largely confined to neutropenic patients with hematologic malignancy. PMID- 1917031 TI - Swedish Study Group. A randomized multicenter trial to compare the influence of cefaclor and amoxycillin on the colonization resistance of the digestive tract in patients with lower respiratory tract infection. AB - Eighty-four patients with lower respiratory tract infections participated in a randomised double-blind parallel multicenter trial in order to compare the efficacy of cefaclor and amoxycillin as treatment for lower respiratory tract infections and their ability to influence colonization resistance. Cefaclor was given to 40 patients and amoxycillin to 44 patients perorally in doses of 250 mg t.i.d. for seven days in a double-blind fashion. Sputum, oropharyngeal and intestinal specimens were taken for microbial analysis to isolate the causative pathogen of the lower respiratory tract infection and to follow the microflora changes before, during and after antibiotic treatment. The clinical outcome showed 92.5% cured or improved patients on cefaclor versus 88.4% on amoxycillin. The difference in clinical outcome between the two treatment groups was not statistically significant. Among the pathogenic bacteria isolated, Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae dominated. There was no difference between the two treatments with regard to microbiological efficacy. Treatment with cefaclor did not cause any significant impact on the oropharyngeal microflora. Administration of amoxycillin caused a significant reduction of the number of Streptococcus salivarius and Veillonella cocci, while an increase in number of enterobacteria was seen in the oropharyngeal microflora. In the intestinal flora, cefaclor significantly reduced the number of streptococci, staphylococci and anaerobic cocci, while the number of enterococci, enterobacteria, bacteroides and Candida albicans significantly increased. The intestinal microflora was partly influenced by amoxycillin treatment. Thus there was a significant increase in the number of enterobacteria, anaerobic gram positive rods and bacteroides. In conclusion, none of these agents caused any major disturbances in the colonization resistance in patients with lower respiratory tract infections. PMID- 1917033 TI - Hepatitis C virus antibodies among risk groups in Turkey. AB - In order to determine the prevalence of hepatitis C virus (HCV) infection in the Black Sea region in Turkey, 287 serum samples taken from risk groups were investigated for anti-HCV antibodies using HCV EIA system. Anti-HCV antibodies were found to be positive in 51.2% of chronic haemodialysis patients, 20.6% of probable acute non-A, non-B hepatitis patients, 4% of patients who had multiple blood transfusions, 1.5% of the health personnel, while in new haemodialysis patients anti-HCV antibodies were not found. PMID- 1917032 TI - Supplemental immunoglobulin (ivIgG) treatment in 163 patients with sepsis and septic shock--an observational study as a prerequisite for placebo-controlled clinical trials. AB - In a multicenter observational study of 163 medical and surgical patients with a total of 173 episodes of sepsis or septic shock (Elebute sepsis score: 19.0 +/- 0.5), the effects of supplemental i.v. immunoglobulin (i.v. IG) treatment (unmodified polyvalent IgG pH 4.25, n = 123; for Pseudomonas sepsis, n = 50, Pseudomonas IgG) on multiple organ failure (MOF) were investigated by means of APACHE II score changes (pretreatment: 23.7 +/- 0.6). In 44% of the cases ("responders"), a prompt improvement in APACHE II score (defined as decrease greater than or equal to 4) was evident from day 0 to day 4 after onset of therapy, thus being in close time relationship to the i.v. IG administration. This improvement, associated with a better prognosis (mortality 24% vs. 55%), was found in all subgroups, most importantly the following: polyvalent IgG vs. Pseudomonas IgG treatment; medical vs. surgical patients; moderate vs. severe MOF; and gram-positive vs. gram-negative septicemia. In a small-sized second comparative nonrandomized control group (n = 27, antibiotic treatment alone) of septic patients (Elebute: 14.7 +/- 1.0) with similar MOF severity (APACHE II: 23.6 +/- 1.4), the response rate (30%) was, though not statistically significant, lower by one-third. The optimal baseline score ranges for patient inclusion into future placebo-controlled randomized i.v. IG trials were found to be 20-35 for the APACHE II score and 12-27 for the Elebute score. PMID- 1917035 TI - Social, economic and psychological impacts of childhood diseases subject to immunization. PMID- 1917034 TI - Infections and other illnesses of children in day-care centers in Helsinki. I: Incidences and effects of home and day-care center variables. AB - Illnesses among children attending municipal day-care centers (DCCs) were followed in a prospective study in Helsinki during 1985-1986. The study comprised 1,905 follow-up years among children in 29 DCCs. The mean number of illness periods was 4.9 per follow-up year, 7.9 for those under the age of three years and 3.8 for older children. The corresponding average numbers of days of illness were 23, 39 and 17. The most common diagnoses were upper respiratory tract infections (46.0%), diarrhea (17.2%), otitis media (12.9%), eye infections (4.0%), acute tonsillitis (3.2%), and bronchitis (3.0%). The six most common diagnoses, all infections, caused 86% of periods and 79% of days of illness. The ten most common infectious diseases caused 90.9% of absence periods, surgical operations 1.8%, and injuries 0.8%. In children under three years of age, a small area and volume of a DCC, lack of fully mechanized ventilation, and lack of separate facilities were associated with a higher incidence of one or all of the six most common infections. A large number of children at a DCC and small homes were associated with a high incidence of one or all of the most common infections among both younger and older children. The effects of passive smoking, number of siblings, number of household members, and incomes of families were not statistically significant. PMID- 1917036 TI - In situ amplification of single copy gene segments in individual cells by the polymerase chain reaction. AB - A method is described using the polymerase chain reaction (PCR) to amplify defined nucleic acid strands in individual cells in situ in conventional smears of bone marrow and peripheral cells. Using radioactively labeled precursors, the incorporation into newly synthesized strands by PCR can be detected by microautoradiography. The specificity of the method can be monitored by gel electrophoresis of the material shed into the reaction mixture. Thus it could be shown that even single genes in individual cells can be amplified to visibility. In a mixture of HIV infected and non infected cells both can be clearly distinguished from one another. PMID- 1917037 TI - Facial palsy with elevated protein in otherwise normal CSF in a child with Lyme disease. AB - This is a report on an eight-year-old girl who presented with facial palsy, headache, fatigue, arthralgias and myalgias six weeks after two tick bites. Physical examination was unremarkable with the exception of a left-sided facial palsy. Laboratory investigation revealed normal complete blood count, ESR and CRP. The spinal tap showed a protein of 63 mg/dl, glucose 45 mg/dl and no cells. IFT titres to Borrelia burgdorferi in serum and CSF were significantly elevated. The diagnosis was supported by Western blot analysis. Treatment was started with ceftriaxone i.v. for a total of 14 days. Under this therapeutic regimen the patient improved substantially within five days. Investigation of CSF in patients with facial palsy may help to establish the diagnosis of Lyme disease by simultaneously measuring IFT to B. burgdorferi in serum and spinal fluid, even in cases where CSF shows little or no signs of inflammation. PMID- 1917038 TI - Prosthetic valve endocarditis caused by Corynebacterium pilosum. AB - A case of prosthetic valve endocarditis caused by Corynebacterium pilosum in a 79 year-old woman developed eighty years after aortic valve replacement with bovine pericardium bioprosthesis is described. In spite of the antibiotic therapy she presented an unfavourable course that led to her death. PMID- 1917039 TI - Acute hepatitis C virus superinfection followed by spontaneous HBeAg seroconversion and HBsAg elimination. AB - Acute hepatitis C virus superinfection followed by spontaneous hepatitis B e antigen seroconversion and hepatitis B surface antigen clearance in a patient with chronic type B hepatitis is described. The observations suggests that HCV may exert a suppressive effect on hepatitis B virus. PMID- 1917040 TI - Acute obstructive respiratory diseases in infants and children associated with parvovirus B19 infection. PMID- 1917042 TI - Salmonella typhimurium infection leading to acute interstitial nephritis. PMID- 1917041 TI - Unusual aminoglycoside susceptibility pattern and mechanisms of resistance of Serratia marcescens strains from Italy. PMID- 1917043 TI - Lyme borreliosis: ten years after discovery of the etiologic agent, Borrelia burgdorferi. AB - Since the recovery of its causative agent, Borrelia burgdorferi, in 1981, Lyme borreliosis has become the most prevalent tick-borne disease in the United States as well as in Europe. Its steadily increasing clinical spectrum now includes erythema migrans, acrodermatitis chronica atrophicans, lymphadenosis beniga cutis, arthritis, myocarditis, progressive meningoencephalitis, myositis, and various ocular and skin disorders. The true incidence of Lyme borreliosis in the world is unknown. In the United States, it has increased from 2,000 cases in 1987, to more than 8,000 in 1989. It occurs now in regions where the tick vectors, Ixodes dammini and Ixodes pacificus, are absent and where other species of ticks may be responsible for maintaining and distributing the spirochete. In Europe, Lyme borreliosis has been reported from 19 countries; its occurrence coincides with the distribution of the vector tick, Ixodes ricinus and possibly Ixodes hexagonus. Specific and dependable serological tests are still not available, but development of probes for specific antigens and the polymerase chain reaction appear promising in detecting ongoing infections and in identifying B. burgdorferi in ticks, animal, and human hosts. Brief reference is made to advances in the preparation of whole cell and genetically engineered vaccines. PMID- 1917044 TI - Laboratory diagnosis and seroepidemiology of Lyme borreliosis. AB - Laboratory diagnosis of Lyme borreliosis is performed by direct detection of Borrelia burgdorferi in body fluids and tissue samples. This can be achieved by cultivation of the organisms, staining techniques, or demonstration of parts of the genome. Although the best aetiologic proof in case of positivity, these methods cannot yet serve as routine techniques: they are too time consuming and expensive. Currently, the usual method for establishing the diagnosis of Lyme borreliosis is serologic testing (indirect detection). Immunofluorescence, hemagglutination, ELISA tests with whole cell antigen should be considered as screening methods. Assays with selected fractions of B. burgdorferi antigens or tests using selected recombinant antigens should be considered as more specific. Immunoblotting (Western blotting) may be considered as a confirmatory test. However, the interpretation of test results requires an experienced investigator. Laboratory diagnosis of B. burgdorferi infections of the central nervous systems (CNS) is the most highly developed method. Demonstration of intrathecally produced specific antibodies, and, moreover, demonstration of specific oligoclonal bands may very well prove the actual infection of the CNS and/or the nerve roots. Seroepidemiological investigations identify neurological manifestations as the most frequent ones among European cases of Lyme borreliosis. The true incidence and prevalence of Lyme borreliosis, however, cannot be determined with current diagnostic methods and must await the development of methods to identify actual infection. PMID- 1917045 TI - Lyme borreliosis of central nervous system (CNS) in children: a diagnostic challenge. AB - Within 24 months in a consecutive series of 84 children with neurological symptoms indicative of Lyme borreliosis of the central nervous system (CNS) 45 seronegative children (group III), 17 seropositive (group II), and 22 children with specific Borrelia burgdorferi results in cerebrospinal fluid (CSF)-i.e. B. burgdorferi antibodies and/or intrathecally produced B. burgdorferi antibodies and/or positive B. burgdorferi culture in CSF were observed. The results show that intrathecally produced B. burgdorferi antibodies are the most important marker for the diagnosis of neuroborreliosis (with 71.4% positives) and B. burgdorferi cultivation directly from CSF may be successful in the earliest phase of the disease. Since each of the specific CSF parameters may be false negative in some cases, a careful synopsis of laboratory parameters was done. It shows that CSF protein and CSF cell values are higher in group I than in II or III. Neither can seronegativity exclude nor can seropositivity confirm the diagnosis of neuroborreliosis as in only 71% of group I serum B. burgdorferi antibodies were detected. In view of these aspects clinical and laboratory results are discussed. PMID- 1917046 TI - Penicillin G sodium and ceftriaxone in the treatment of neuroborreliosis in children--a prospective study. AB - A controlled clinical study was set up to examine whether penicillin G sodium (PG) or ceftriaxone (C) is superior in the treatment of acute neuroborreliosis in childhood. Within a time period of 18 months 77 children with symptoms indicative of Lyme borreliosis of the central nervous system (CNS) were seen. In 23 of these children Borrelia burgdorferi specific cerebrospinal fluid (CSF) parameters confirmed the diagnosis of a neuroborreliosis. These children were treated at random with intravenous (i.v.) PG 400,000-500,000 I.U./kg/day for 14 days (group I) or with i.v. ceftriaxone 75-93 mg/kg/day for 14 days (group II), respectively. Clinical examination and a set of diagnostic laboratory parameters were done at admission, right after therapy, three, six and partly 12 months after therapy. The general condition of all children in both groups improved dramatically during antibiotic therapy, and no relapse occurred within the observation period. Considering the clear and comparable decrease of B. burgdorferi serum titres and the clinical outcome (duration of disease and follow-up for at least six months) in children of both groups no difference between both antibiotic drugs can be demonstrated. PMID- 1917047 TI - Cutaneous manifestations of Lyme borreliosis. AB - The dermatological symptoms of Lyme borreliosis present with a typical clinical pattern and characteristic time of appearance. In contrast to other manifestations of Lyme borreliosis they are easily recognizable in most of the cases. In the first stage, erythema migrans arises at the tick bite site. With this symptom the diagnosis of Lyme borreliosis can be established. During all manifestations of Lyme borreliosis the history of erythema migrans is an important parameter to verify the diagnosis. In the early stage of disease a lymphocytic proliferation can appear at the tick bite site, at the ear lobe, or at the mamilla. Borrelia lymphocytoma can be diagnosed when antibodies against Borrelia burgdorferi are positive. Years after infection, acrodermatitis chronica atrophicans arises at distal body sites causing livid swelling and gradually skin atrophy. Skin lesions can be accompanied by neuropathies, mostly of the lower legs, which in contrast to the skin lesions, do not respond well to antibiotic therapy. There is evidence that some cases of Shulman syndrome, morphea and lichen sclerosus et atrophicus might be related to a borrelia infection as indicated by cultivation of B. burgdorferi from skin biopsies of morphea and response to antibiotic treatment in some cases. The classical dermatological symptoms of Lyme borreliosis, erythema migrans, borrelia lymphocytoma and acrodermatitis chronica atrophicans respond to oral antibiotic treatment. In acrodermatitis chronica atrophicans parenteral antibiotic therapy is sometimes necessary. PMID- 1917048 TI - Preliminary characterization of Borrelia burgdorferi CSF isolates. AB - Borrelia burgdorferi was cultivated from three cerebrospinal fluid (CSF) samples of children (aged three and a half, four and a half and eight years) who were admitted to the hospital because of acute facial palsy, aseptic meningitis, and aseptic meningitis plus facial palsy. CSF was taken on day one in two cases and on day two in the remaining case after onset of symptoms. All three strains showed a very similar SDS-PAGE pattern, without an OspB and 20kD band. However, of nine monoclonal antibodies (Moab) raised against B. burgdorferi B31, the Moab H5332 recognized two strains, one of them very weakly, and the flagella specific Moabs H9724, H605, and H6TS (less intensively) recognized all strains. This preliminary characterization reveals heterogeneity among CSF Borrelia isolates of cases from a very close geographic area. PMID- 1917050 TI - Rufloxacin once daily in acute exacerbations of chronic bronchitis. AB - In this open study the efficacy and tolerability of rufloxacin in a single dose of 400 mg the first day and 200 mg the nine consecutive days was studied in 26 patients with an acute exacerbation of chronic bronchitis. Twenty-two patients were evaluable for efficacy. Four patients stopped treatment prematurely after five days because of clinical cure. At the enrollment visit a pathogen was isolated in the sputum sample in 19 of 22 evaluable patients. The predominant pathogens were Streptococcus pneumoniae and Moraxella catarrhalis. In 17 of these 19 bacteriologically evaluable patients the initial infecting organism was eradicated from specimens obtained within 48 hours after the end of therapy. There was one case of persistent infection caused by S. pneumoniae (MIC 4 mg/l), one patient had a superinfection with Serratia marcescens (MIC 1 mg/l) susceptible to rufloxacin and therapy was stopped after five days due to clinical failure. One week after the end of therapy, 15 patients remained free from infection whilst one patient experienced reinfection with Klebsiella pneumoniae (MIC 0.5 mg/l). Clinical cure or improvement was observed in 21 of 22 patients. Mild adverse events were reported by two of 26 enrolled patients. In one patient, complaining of headache and dizziness, the adverse events were considered possibly study drug related. No abnormal laboratory findings were reported. Nadir plasma levels of rufloxacin were measured and no accumulation in plasma was observed during treatment. A ten day course of an oral single dose of rufloxacin proved efficacious and was well tolerated in patients with an acute exacerbation of chronic bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917051 TI - [Postoperative nitrogen loss]. AB - Total nitrogen excretion was studied prospectively in 54 surgical patients during the first and second postoperative day by the Chemiluminescence method. The results were compared to three different methods for approximation of the total nitrogen excretion. Daily total nitrogen excretion was 13.13 +/- 5.7 g after peripheral vascular procedures, 15.97 +/- 8.1 g after major surgical procedures and 20.42 +/- 5.2 g in septic patients. The assessment of total nitrogen excretion by the three other methods underestimated real nitrogen losses by 20 52%. The nitrogen concentration in various secretions was relatively constant. We conclude that measuring the urine nitrogen losses only and adjusting them for the calculation of the total nitrogen excretion by several factors in incorrect. Direct measurement of total nitrogen excretion is too costly for the use in daily clinical practice. PMID- 1917049 TI - Safety of ciprofloxacin in children: worldwide clinical experience based on compassionate use. Emphasis on joint evaluation. AB - Six hundred and thirty four adolescents and children aged three days to 17 years treated with ciprofloxacin on a compassionate basis were analysed for drug safety. 62% of the ciprofloxacin courses were given to patients with respiratory tract infection, primarily those with acute pulmonary exacerbation of cystic fibrosis. The mean daily oral dose was 25.2 mg/kg body weight. The duration of treatment ranged from one to 880 days (mean 22.8 days). Because of the arthropathogenic potential of quinolones in juvenile animals special emphasis was placed on the evaluation of musculoskeletal adverse events. Arthralgia considered by the treating physicians to be related to ciprofloxacin was reported in eight children, all of whom were females. Arthralgia resolved in all children. Some of these children were given subsequent courses of ciprofloxacin with no complaints of arthralgia. Overall, the safety profile of ciprofloxacin in children is not substantially different from that of adults. PMID- 1917052 TI - [Infusion mixtures--study of clinical practice in Austria]. AB - Options in parenteral therapy increasingly require administration of several medications simultaneously. Very little is known about the compatibility and pharmacological stability of such mixtures. We investigated how widespread this practice is, which carrier solutions are most commonly used, and whether specific medication mixtures ('cocktails') or constant formulations for TPN are applied. Upon our request, physicians and nursing staff of 54 general hospital wards (19 surgical, 18 internal medicine, 17 intensive care) in 17 Austrian hospitals recorded the parenteral admixtures for one week under the supervision of a hospital pharmacist. We found that: 1. Admixing is commonly practiced in all wards. In all but one of the wards two or even more medications are added into one single infusion. 2. Carrier solutions were: Dextrose/fructose (87% of the wards), electrolytes (90%), amino acids (40%), fat emulsions (26%), colloids (14.8%), albumin (5.5%) and Solcoseryl (5.5%). 3. Fixed combinations for i.v. therapy are practiced in 70% of the wards (mostly analgetics with corticosteroids or vitamins) 4. In almost half of the units constant formulations for TPN exist (46%). Only few of the combinations named have been investigated or tested for stability. The compatibility of most of the admixtures is unknown, while a few are clearly incompatible. Admixtures to one of the carrier solutions (Solcoseryl) are known to have caused serious complications before. For several admixtures, conflicting data about compatibility were found in the literature. The theoretical basis for incompatibilities is discussed together with some typical examples. Also some rules for admixtures are given. Questions concerning the compatibility of simultaneous parenteral drug applications are too specific to be answered for most physicians. Advice and counseling on this subject should become a new task for clinical pharmacists. PMID- 1917053 TI - [Does varied parenteral zinc administration modify interaction between tumor and host? Studies based on an animal model]. AB - Zinc speeds up a lot of metabolic processes because it is essential for a lot of enzymatic reactions. A modification of the zinc pool may influence the tumor growth. We used an animal model where we applied the Yoshida sarkoma intraperitoneally in its ascites form to parenterally fed Sprague-Dawley rats. Four groups with ten tumor bearing (TBR) and ten non-tumor-bearing rats (NTBR) each received different parenteral nutrition. The normocaloric Group 1 and the hypocaloric (reduced to 1/3 energy) Group 2 were fed without zinc. In Groups 3 (normocaloric) and (hypocaloric) high doses of zinc (0.519 mg/500 g Kg/d) were substituted. In Group 3 we found the quantitatively and qualitatively highest proof of tumor mass. The nitrogen content of the ascites wasn't significantly changed within the groups. We found a weight loss of the NTBR with zinc substitution. Zinc improves the synthesis of the tumor and leads to a weight loss of the host in our animal model. PMID- 1917054 TI - [A new method for the determination of circulating blood volume--erythrocyte marking with sodium fluorescein]. AB - The knowledge of circulating blood volume extends the possibility of judgement of the circulation status and is a valuable help for the management of volume therapy. Blood volume measurements are rarely done in clinical practice in underestimation of their value for the therapy because of their high technical expense, long duration of examination, bad repeatability and radiation exposure. A method for blood volume determination which possesses more favorable abilities than known radioactive methods has been developed by staining red cells with fluorescein sodium. This paper presents an insight into the method and examines the reliability of measurement by means of repeated determinations in vivo. PMID- 1917055 TI - [Storage of thrombocyte concentrates: ultrastructural and functional changes]. AB - Optimal storage of platelet concentrates is still an unsolved problem. The present paper demonstrates changes in morphology and function of stored platelets. Transmission microscopy reveals a loss of organelles as well as a progredient destruction of cell membranes during storage. At the same time in vitro aggregability is clearly diminished. Therefore, further investigations seem to be necessary to improve storage conditions of platelets. PMID- 1917056 TI - [Tumor cell separation by cell saver and membrane filter passage]. AB - Definite suspensions of malignant cells from three human tumor cells lines (bladder, prostate and renal cell carcinom) were passed through a cell saver (Althin Mediplast) and a leucozyte removal filter (PALL RC 100) under standard conditions. The examination of the solutions did not detect any malignant cells at all. If investigations with malignant cells in the blood will confirm these results, the use of intraoperative autotransfusion in urological tumor surgery would be possible. PMID- 1917057 TI - Impact of leukocytes on the storage of platelet concentrates. PMID- 1917058 TI - Is leukocyte depletion important in the prevention of alloimmunization by random single donor platelet transfusions? PMID- 1917059 TI - Filtration of platelet concentrates. AB - The transfusion of leukocyte-containing blood products causes a number of side reactions, which among others induces alterations of the immune system of the recipient leading to alloimmunization or immunosuppression. Antibodies against antigenic determinants of the major histocompatibility complex-proteins of class I are the major cause of alloimmunization. Though platelets are easy targets for HLA antibodies, they cannot induce the antibody production themselves. This requires leukocytes, carrying the MHC-proteins of the class II. Standard platelet concentrates for the clinical routine have more than 10(6) leukocytes. Leukocyte filters with a special surface modification reduce the number of leukocytes in platelet concentrates underneath this CILL-value (critical immunogenic load of leukocytes), thus reducing the antigenic, immunogenic effects of leukocyte contamination considerably. PMID- 1917060 TI - Plateletpheresis with the new COBE Spectra. AB - The COBE Spectra was evaluated in 71 plateletpheresis procedures. Using the collection and anticoagulant algorithms of the system (n = 57) we collected 4.3 +/- 1.2 x 10(11) platelets with a mean separation efficiency of 70.2 +/- 12.1%. The cell contamination was very low (leukocytes 0.5 +/- 1.0 x 10(7), red cells 1.5 +/- 2.2 x 10(7]. In four different modifications of the standard separation protocols, we tried to reduce the ACD consumption in order to shorten the donation time and to improve donor safety. A constant ACD/blood ratio of 1:9 and increase of the blood flow to 50 ml/min (n = 14) caused significantly lower yields (3.1 +/- 0.7, p less than 0.01) and visible spontaneous platelet aggregates in the collection line in 50% and in the PC's in 29% of the runs. In order to prevent platelet activation the ACD algorithm had to be maintained, but a reduction of the ACD/blood ratio to about 15% was acceptable. PMID- 1917061 TI - The Enhancement Package for the COBE Spectra Apheresis System. PMID- 1917062 TI - Principles for storage of platelet concentrates. PMID- 1917063 TI - Future technologies in transfusion medicine. PMID- 1917064 TI - Ubiquitous pollution by n-hexane and reference biological levels in the general population. AB - n-Hexane levels were determined by gas chromatography and mass spectrometry in environmental air and in the alveolar air, blood and urine of a group of subjects aged on average of 38 years who had not been occupationally exposed to this hydrocarbon. n-Hexane was found in all environmental air samples examined (n = 49), with the mean concentration being 104 ng/l (limit values, 1-279 ng/l). It was also found in all 49 samples of alveolar air, with the mean concentration being 50 ng/l (variation limit, 1-304 ng/l). In 64 samples of urine, n-hexane was found in only 50 samples, with the mean concentration being 1,417 ng/l (limit values, 34-8,820 ng/l). In 77 of the 90 blood samples taken, a mean concentration of 608 ng/l was detected (variation limit, 15-7,684 ng/l). Particularly the haematic and urinary concentration showed significant differences among the nine groups of individuals classified according to their work activity. The lowest levels were found in the blood and urine of farmers: 270 and 298 ng/l, respectively. The highest values were found for chemical workers (1,377 and 411 ng/l), respectively printers (585 and 2,691 ng/l respectively), and traffic wardens (740 and 8,820 ng/l, respectively). In all, 95% of the determinations of n-hexane yielded values of less than 255 ng/l in environmental samples, less than 105 ng/l in alveolar air, less than 1,475 ng/l in blood and less than 5,875 ng/l in urine. A comparison of these data revealed a significant correlation between environmental levels and alveolar (r/s = 0.769; P less than 0.00001), haematic (r/s = 0.624; P less than 0.0002), and urinary (r/s = 0.597; P less than 0.0005) values for n-hexane. PMID- 1917066 TI - Environmental and biological monitoring of non-occupational exposure to 1,3 dichloropropene. AB - Voluntary bystanders, simulating a situation of non-occupational exposure to Z- and E-1,3-dichloropropene (Z- and E-DCP), were exposed during field application of this nematocide in the Dutch flower-bulb culture. Environmental monitoring revealed that mean respiratory exposure concentrations of Z- and E-DCP varied from non-detectable levels to 1.12 mg/m3 8-h time-weighted average (TWA) for Z DCP and to 0.91 mg/m3 8-h TWA for E-DCP. Biological monitoring was executed by determining urinary mercapturic acid metabolites of Z- and E-DCP according to a method recently validated in occupationally exposed applicators. A linear relationship between respiratory exposure to Z- and E-DCP and the urinary excretion of both mercapturic acids was observed in bystanders. Dermal uptake did not contribute significantly to the internal dose of Z- or E-DCP. The urinary mercapturic acid of Z-DCP was a more sensitive parameter for the detection of exposure than was respiratory air monitoring. In future studies it would be worthwhile to determine the extent of exposure of real bystanders to DCP on the basis of urinary mercapturic acid excretion. PMID- 1917065 TI - Biological monitoring of environmental and occupational exposure to mercury. AB - Biological monitoring was used to assess mercury exposure from occupational and environmental sources in a group of chloralkali workers (n = 89) and in a control group (n = 75). In the control group, the median value for blood mercury (B-Hg) was 15 nmol/l, that for serum mercury (S-Hg) was 4 nmol/l and that for urinary mercury (U-Hg) was 1.1 nmol/mmol creatinine. Corresponding levels in the chloralkali group were 55 nmol/l, 45 nmol/l and 14.3 nmol/mmol creatinine, respectively. In the control group, there were statistically significant relationships between fish consumption and both B-Hg and S-Hg values (P less than 0.001), whereas U-Hg correlated best with the individual amalgam burden (P less than 0.01). In the chloralkali group, the mercury levels in blood and urine were significantly related to the type of work (P less than 0.001) but not to the length of employment, to fish consumption or to the quantity of dental amalgam fillings. In both groups there were poor correlations between smoking or alcohol intake and the mercury levels in blood and urine. The results strongly suggest that fish is an important source of methylmercury exposure and that amalgam fillings are probably the most important source of inorganic mercury exposure among occupationally unexposed individuals. In the chloralkali group, mercury exposure from fish and amalgam was overshadowed by occupational exposure to inorganic mercury. PMID- 1917067 TI - Impeded lung function in moulders and coremakers handling furan resin sand. AB - A total of 39 moulders and coremakers exposed to furan resin sand and 27 unexposed local controls were examined by lung-function tests before and after a work shift. In all, 28 of the subjects exposed to furan resin sand and the control group were evaluated by dynamic spirometry and nitrogen washout. The remaining 11 subjects exposed to furan resin sand were studied using both static and dynamic spirometry and the CO single-breath technique. The time-weighted average exposure to furfuryl alcohol was about 7 mg/m3, with peak values exceeding the present Swedish short-term exposure limit (40 mg/m3). The exposure to respirable dust and formaldehyde as time-weighted over the shift was less than 2 mg/m3 and 0.4 mg/m3, respectively, in all groups. During the work shift studied, the 28 exposed subjects had more complaints of airway symptoms than did the controls, showing an average decrease of 0.21 in forced vital capacity but no fall in any other lung-function variable. The remaining 11 exposed subjects demonstrated a post-shift decrease in total lung capacity. The results indicate an acute restrictiveness induced by exposure to furan resin sand, but the underlying mechanism is unclear. Chronic impairment of lung function was not observed. PMID- 1917068 TI - Determination of tetrahydrophtalimide and 2-thiothiazolidine-4-carboxylic acid, urinary metabolites of the fungicide captan, in rats and humans. AB - Capillary gas chromatographic (GC) methods using sulphur and mass selective detection for the qualitative and quantitative determination of tetrahydrophtalimide (THPI) and 2-thiothiazolidine-4-carboxylic acid (TTCA), urinary metabolites of the fungicide captan in rat and humans, were developed. Urinary detection limits were 2.7 micrograms/l for THPI and 110 micrograms/l for TTCA. Intraperitoneal and oral administration of captan to rats resulted in a 48 h cumulative urinary excretion of THPI of 1%-2% and 3%-9% of the dose, respectively. Cumulative urinary excretion of TTCA over 48 h ranged from 2% to 5% of the captan dose for the respective routes of administration. In urine of non exposed human subjects, neither THPI nor TTCA could be detected. In urine of fruit-growers who were occupationally exposed to captan, both THPI and TTCA could be detected. Based on these results, THPI and TTCA are proposed as promising parameters for the biological monitoring of occupational exposure to captan. PMID- 1917069 TI - Mobilized mercury in subjects with varying exposure to elemental mercury vapour. AB - In a mercury mobilization test, 0.3 g of the complexing agent sodium 2,3 dimercaptopropane-1-sulfonate (DMPS) was given orally to 10 workers with moderate occupational exposure to elemental mercury vapour, to 8 dentists with slight exposure, to 18 matched controls, and to 5 referents without amalgam fillings. In the workers, DMPS caused an increase in 24-h urinary mercury excretion by a factor of 10; in the dentists, 5.9; in the controls, 5.3; and in the amalgam-free referents, 3.8. Of the mercury excreted during 24 h, 59% appeared during the first 6 h. Close, albeit non-linear, associations were found between mobilized mercury and the premobilization mercury levels in plasma and urine, but not with the duration of occupational exposure or the rough estimate of the integrated function of blood levels vs time. The present data indicate that mercury mobilized after a single DMPS dose in close connection with exposure is mainly an index of recent exposure and is not significantly affected by slow body pools or long-term exposure. PMID- 1917070 TI - Metal concentrations in lung tissue of subjects suffering from lung cancer. AB - Concentrations of nine metals (Fe, Ca, Mg, Zn, Cu, Co, Ni, Pb and Cr) concentrations in lung tissues from 224 lung cancer cases were compared with those in other cases to achieve an understanding of their contribution to the development of lung cancer and the varieties after the development of cancer. Comparisons of metal concentrations in each cell type of lung cancer were also performed. All cases were collected from routine autopsies in Tokyo and Saitama, Japan. The copper concentration in tissue from lung cancers was significantly higher than that in other specimens, although calcium, magnesium, zinc and cobalt concentrations in lung cancers were significantly lower than those in other cases. There were no significant differences in the 99% intervals (excluding extremely high values for occupationally exposed cases) for chromium, nickel and lead concentrations between lung cancers and other cases, although these values were lower in lung cancers. However, in comparisons of men only, the chromium concentration, the degree of lung contamination and the severity of pulmonary emphysema in lung cancer cases were significantly higher than those in other specimens. Moreover, percentages of lung cancer in men at each degree of contamination and each severity of emphysema increased with increasing grades. Thus, this finding could be evidence that the exposure to contaminants other than chromium and nickel in the air had affected the development of lung cancer, except for occupationally exposed individuals. Therefore, almost all chromium and nickel in lung tissue might not deposit in carcinogenic forms such as hexavalent chromium or nickel subsulfide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917073 TI - Effect of vibration frequency on finger blood flow. AB - A total of 18 healthy subjects (9 men and 9 women) 20-35 years of age were used to study the effect of vibration frequency on finger blood flow. Seven vibration frequencies of 16, 31.5, 63, 125, 250, 500 and 1,000 Hz, at vibrational accelerations of 10 m/s2 (rms: root mean square) or 50 m/s2 (rms), with the exception of 16 Hz, which was measured at only 10 m/s2 (rms), were randomly applied to the palm of the right hand for 1 min at intervals of about 3 min. Finger blood flow was measured simultaneously in both the right and the left middle fingers with a blood flowmeter using a thermal diffusion method and in the left middle finger with a laser Doppler flowmeter. The experiments were performed in an artificial climate chamber set at 23 degrees C air temperature and 50% humidity. Relatively great responses were observed at frequencies of 31.5-63 and 250-500 Hz on the exposed and unexposed sides, respectively, as measured with a blood flowmeter using a thermal diffusion method and at 31.5-63 as well as 500 Hz on the unexposed side with a laser Doppler flowmeter. These results may be related to Meissner's and pacinian corpuscles. PMID- 1917071 TI - Serum IgE and lung function in workers exposed to phthalic anhydride. AB - A total of 23 phthalic anhydride (PA)-exposed workers (air levels up to 17 mg/m3) showed significantly (P less than 0.01) more workrelated symptoms in their eyes (48% vs 6%) and nose (39% vs 0) than did 18 unexposed control subjects. Two of the exposed workers had PA-associated asthma. Surprisingly, the control group exhibited significantly (P less than 0.05) more symptoms of nonspecific bronchial hyperreactivity (44% vs 13%). The exposed workers showed significantly higher levels of total serum IgE (medians, 32 vs 15 kIU/l, P less than 0.05), although values for specific IgE against PA did not differ. This may indicate that such exposure can facilitate the entry of common allergens. There was a significant difference in PA-specific IgG [enzyme-linked immunosorbent assay (ELISA) ratios 0.21 vs 0.12; P less than 0.01]. There were no differences in lung function with regard to vital capacity (VC) and forced expiratory volume (FEV1), closing volume expressed as a percentage of VC (CV%), volume of trapped gas (VTG) before and after inhalation of metacholine, or carbon monoxide transfer factor (TLCO), whereas exposed workers displayed significantly higher late expiratory flow rates (MEF50 and MEF25). In a [99mTc]-diethylenetriamine penta-acetate (DTPA) clearance test, there was no difference between exposed subjects and controls. In summary, exposure to PA did not cause subclinical effects of the lungs. Subjects with lower-airway symptoms showed lower FEV1, MEF50, and MEF25 values and higher VTG (after metacholine) than did those without symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917072 TI - 2-Acetylfuran, a confounder in urinalysis for 2,5-hexanedione as an n-hexane exposure indicator. AB - The apparent amount of 2,5-hexanedione, a biomarker of n-hexane expsoure in occupational health, in the urine of both exposed and non-exposed subjects varied not only as a function of the pH at which the urine sample was hydrolyzed but also depending on the capillary column used for gas chromatographic (GC) analysis of the urinary hydrolyzates after extraction with dichloromethane. The formation of a compound, identified by gas chromatography-mass spectrometry (GC-MS) as 2 acetylfuran, following acid hydrolysis was a major cause of confounding effects. This compound was hardly separated from 2.5-hexanedione on a capillary column such as DB-WAX, whereas separation could be achieved on a DB-1 capillary column. 2-Acetylfuran was formed when a urine sample was heated at a pH of less than 2 for hydrolysis, and the amount detected in urine did not differ between exposed and non-exposed subjects, indicating that the formation of 2-acetylfuran is independent of n-hexane exposure. When urinary hydrolysis is used, hydrolysis at a pH of less than 0.5, extraction with dichloromethane, and GC analysis on a non polar capillary column are proposed to be the best analytical conditions for 2,5 hexanedione analysis in biological monitoring of exposure to n-hexane. PMID- 1917074 TI - Individual response to physical work in the heat in relation to sweating and skin blood flow. AB - The aim of the present study was to examine heart rate and rectal temperature responses to dynamic exercise in a hot environment and their relationship to sweating and skin blood flow. Eight physically trained men were the study subjects. The experiments consisted of 60-min bicycle ergometer tests at intensities of 50 and 100 W in the heat (36 degrees C/30% relative humidity). During the tests, oxygen consumption, heart rate, rectal temperature, and skin temperatures on eight sites were measured. The whole-body sweat rate and evaporation rate and the rate of dripping sweat were measured by a continuous weighing technique. Skin blood flow was estimated from the changes in forearm blood flow. In all, 13 tests were done at 50 W and 10 tests were conducted at 100 W. At 50 W, a physiological steady state was attained in all tests, i.e. the rise in heart rate was less than 10 beats min-1. At 100 W, in all experiments the heart rate and rectal temperature increased continuously throughout the tests. At the end of exercise, the heart rate varied from 98 to 150 beats min-1. At 50 W work load, the heart rate and rectal temperature did not significantly correlate with any of the thermoregulatory parameters. At 100 W, the heart rate and rectal temperature correlated with the total sweat rate (r = -0.66 and -0.71, respectively; P less than 0.05), with the onset of dripping (r = 0.74 and 0.66, respectively, P less than 0.05), and with the ratio of forearm blood flow to dripping sweat rate (r = 0.83 and 0.85, respectively; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917075 TI - Criteria for substituting amalgam with composite resins. AB - In recent years patients' aesthetic requirements have increased as knowledge of new materials and techniques has spread. Enamel etching and composite filling materials have enabled dentists to meet high functional and aesthetic standards in the placing of anterior and, latterly, posterior restorations. There has been a dramatic growth in the use of posterior composites and the aim of this paper is to provide the practising dentist with guidelines for the use of these materials. PMID- 1917077 TI - Orthodontic abnormalities in patients with eating disorders. AB - Many anorexic and bulimic patients induce vomiting by inserting their fingers in the oral cavity. We hypothesized that finger pressure could lead to tooth movement, eventually resulting in the development of orthodontic abnormalities, particularly open-bite. Twenty-four females with eating disorders and 24 matched controls underwent orthodontic examination and completed a dental questionnaire. Orthodontic abnormalities were more commonly found in the eating disorder group and open-bite was the most common abnormality seen. The presence of open-bite or other orthodontic abnormality was not associated with patient reports of self induced vomiting, which would suggest that digital pressure was not the causative factor. The dental appearances indicated that the skeletal base pattern was abnormal in many cases. The findings could, in part, be accounted for by the fact that patients with eating disorders were less likely than controls to have completed courses of orthodontic treatment. Alternatively, the orthodontic abnormality may have contributed to the development of an eating disorder. Further study of this area is proposed. PMID- 1917076 TI - Potential teratogenic and carcinogenic effects of dental materials. AB - Public awareness of potential health hazards from drugs and chemicals is increasing. Doubts about dental materials are also being raised. However, there is a fundamental difference in the magnitude of exposure from potent drugs and from dental materials, which are designed to be as inert and stable as possible; the risk to health could a priori be considered very low. The risk to the patient and to dental personnel should be evaluated separately and based on relevant conditions of exposure and available toxicological data for the specific chemicals released from the dental materials in question. This paper also reviews, briefly, the theories for chemically-induced teratogenic and carcinogenic effects in general, in order to put into perspective suspected adverse reactions to dental materials. PMID- 1917078 TI - Update on low-calorie sweeteners to benefit dental health. AB - Ten different types of high-intensity, low-calorie sweeteners that have potential dental applications as sugar substitutes are appraised, taking into consideration their general properties, safety and toxicological assessment, metabolic fate in the body, regulatory status and any dental research that has been carried out on them. Attention focuses on the continuing expansion in the wide diversity of types of sweeteners becoming available, the multiple sweetener concept, the growing interest in materials of natural origin, and the distinction between non cariogenic and actively anti-cariogenic properties of the individual sweeteners. PMID- 1917079 TI - Periodontal treatment and prophylaxis in the frail elderly. AB - Throughout the world the numbers of elderly are rapidly increasing. Survival to age 80 years and beyond is now commonplace in many industrialized nations. Of particular concern to the health professions is the previously unimagined growth in the population aged 80 years and over who are at increased risk of morbidity and disability. The rates of edentulism and tooth loss are rapidly declining with a consequent increase in the risk of developing periodontitis. Periodontal treatment and prophylaxis for the frail and the functionally dependent elderly involve a complete analysis of the physical and emotional status of the patient. The effects of chronic conditions, illnesses and medications on the ability of the older patient to accept treatment must be understood if periodontal care is to have a reasonable chance of success. In medically compromised patients and in patients who are unable to maintain oral hygiene, non-surgical periodontal therapy may be the best approach to treatment, although there are alternative routes to treatment as well as prevention. Periodontal diseases can be treated successfully in the aged and periodontal health can be sustained. PMID- 1917080 TI - Replacement complete dentures: no friends like old friends. AB - Provision of replacement complete dentures for an increasingly elderly population presents problems for the dentist. Reduced adaptability in the older person leads to difficulty in learning to use new appliances unless existing skills can be employed. It is therefore helpful to reproduce familiar features of a patient's old appliances, especially if these have been used for some years. This paper describes a method of treatment that provides both clinician and laboratory with the ability to achieve this objective, while retaining freedom to eliminate clinically-identified faults in the old appliances in the process of provision of the new. The technique depends on the substitution of conventional wax-rimmed record blocks with wax replicas of the old appliances. These replica record blocks lend themselves to any - major or minor - alteration during occlusion recording. They also incorporate a rigid baseplate and function as special trays. PMID- 1917081 TI - Founders of the American Association of Women Dentists: their legacy lingers on. AB - Lucy Hobbs was the first women to graduate as a dentist from Ohio Dental College in 1866. By the turn of the century a sufficient number of women had graduated to create a need for the establishment of groups specifically for women in dentistry. The Women's Dental Association of the United States was incorporated in 1892 with 12 founding members, although the name was changed to American Association of Women Dentists (AAWD) in 1928. This paper traces the history of the AAWD and provides some biographical details about the 12 founders. PMID- 1917082 TI - Teeth for life: oral disease prevention in research and practice. PMID- 1917083 TI - Effects of extensive apical reaming and calcium hydroxide dressing on bacterial infection during treatment of apical periodontitis: a pilot study. AB - An apical dentine sampling technique was applied in order to monitor the bacteriology of the pulp canal and radicular dentine before and during treatment of teeth with chronic apical periodontitis. Twenty-three teeth with a radiographic diagnosis of apical periodontitis were studied. They were subjected to a standardized two-appointment treatment regimen of extensive apical reaming in the absence of antimicrobial agents and 1-week dressing with calcium hydroxide. Bacteriological samples were taken from the root canal at the start, and apical dentine samples at the end, of each sitting. Provision was made to allow growth of anaerobic bacteria. All root canals but one showed growth at the start of treatment. Dentine samples were positive in 14 of the 23 teeth at the end of the first appointment. Eight of the 23 canals had detectable growth from the canal at the start of the second appointment, but in sufficient numbers for quantification in only one root canal. The subsequent dentine samples were otherwise negative at the second appointment. There was a tendency for teeth causing symptoms to harbour more bacteria than symptomless teeth. PMID- 1917084 TI - The influence of different root canal instruments on root canal preparation: an in vitro study. AB - Nine endodontic instruments from different manufacturers (Reamers, K-files, Hedstrom files, K-Flex files, Flexofiles, S-files, Burns Unifiles, Flexicut files and Flex-R files) were used to prepare 180 simulated root canals in resin blocks. The instrument's ability to reproduce a theoretical pre-established ideal canal shape was assessed by comparing the original canal path with the resulting enlarged canal shape by a double exposure photographic method. The individual ability of each instrument to transport debris was also observed during instrumentation under a stereomicroscope. Regardless of the instrument type, none was able to reproduce ideal results; however, clinically acceptable results could be obtained with all of them. The coronal and apical debris transportation characteristics proved to be similar with all instruments. PMID- 1917085 TI - Flare-up rate of single-visit endodontics. AB - The purpose of the study was to compare the flare-up rate for single-visit endodontics among teeth without radiographic or clinical signs of apical periodontitis, those with radiographic or clinical signs of apical periodontitis not previously root-treated, and those with apical periodontitis where retreatment was performed. All teeth were instrumented to a predetermined minimum size with a 0.5 per cent solution of sodium hypochlorite being used as the irrigant. The root canal was obturated without regard to the presence or absence of symptoms or diagnosis of the apical condition. The patients were given written post-operative instructions and a prescription for 600 mg ibuprofen to be taken if mild to moderate pain developed. If severe pain and/or swelling developed, the patient was instructed to telephone immediately and was considered to have had a flare-up. Teeth without signs of apical periodontitis did not have any flare-ups. One flare-up occurred in 69 teeth with signs of apical periodontitis not previously root-treated. The majority of the flare-ups (3 of 22 teeth) occurred in teeth with signs of apical periodontitis requiring retreatment. PMID- 1917086 TI - The ability of the radiograph to determine the location of the apical foramen. AB - An in-vitro radiographic study of human teeth was performed in order to evaluate the ability of radiographs to determine the location of the apical foramen. The tip of an endodontic file was positioned at the apical foramen of each canal in 117 extracted human teeth (213 canals) and in 56 teeth (92 canals) still within the alveolus of dried jaw specimens. Parallel radiographs were taken in a bucco lingual plane of all teeth. The tip of the instrument appeared to be at the root surface (apical foramen) in 82 per cent of canals. There was no significant difference in results between the teeth radiographed in the alveolus of dried jaw specimens and extracted teeth when the radiographs were evaluated under a stereomicroscope. PMID- 1917087 TI - Self-replantation of an avulsed tooth: 30-year follow-up. AB - A 42-year-old man had been previously hit in the mouth when he was 12 years old, and the upper left central incisor was completely avulsed. The patient immediately replanted the tooth and did not seek any dental treatment. After 28 years he noticed discoloration and abscess formation. Root canal treatment was performed, and the tooth has remained in a stable, functional position. PMID- 1917088 TI - Class II antigen expressing cells in experimentally induced pulpitis. AB - This study reports on the occurrence of class II antigen expressing cells in inflammatory lesions experimentally induced in the rat incisor pulp. Concanavalin A and lipopolysaccharide of Bacteroides gingivalis were applied to the exposed pulp following a preparation through alveolar bone and dental tissues in the midpart of the root. In a set of control teeth, pulpal exposures were capped with Cavit without the placement of antigenic material. Animals were killed after 3, 12, 24, 48 or 96 hours. Pulp tissue specimens were subjected to immunohistochemical analysis utilizing a monoclonal mouse anti-rat class II antigen antibody. Semi-quantitative assessment of positively stained cells was carried out under the light microscope. Significantly more class II antigen expressing cells were identified in the challenged pulps than in the controls at all experimental periods. The increase in cells peaked at 48 hours to taper off at the subsequent 96-hour observation. The rapid and intense influx of class II antigen expressing cells suggests that these cells are associated with the initial defence of the dental pulp. PMID- 1917089 TI - The effect of post space preparation on the apical seal of root fillings using chemically adhesive materials. AB - The effect on the apical seal of root filling teeth with two sealer cements that reacted chemically with tooth structure was studied in vitro. In addition, apical leakage of teeth obturated with these materials and subsequently prepared to accept a post was tested. Ninety single-rooted teeth with mature apices were prepared chemomechanically by the stepback technique using files and copious irrigation with 2.5 per cent sodium hypochlorite. The teeth were then randomly allocated to six groups of 15 teeth each. Two groups were root filled by lateral condensation of gutta-percha and one of three sealer cements: Tubliseal, a radiopaque glass ionomer luting cement, Ketac Cem, and a chemically active composite resin, Panavia Ex. Thirty minutes later, in one group for each material, a post space was prepared leaving 4-5 mm of root filling at the apex. The extent of apical leakage in each group was determined after immersion in Indian ink for 14 days. The teeth were demineralized, dehydrated and immersed in methyl salicylate, which rendered them transparent, and a linear measurement of dye penetration was recorded. No statistically significant difference in the extent of leakage was found between the sealers in those groups which were filled by lateral condensation and left intact. However, the degree of leakage increased after post space preparation with the glass ionomer and Tubliseal groups, but was reduced in the Panavia Ex group. PMID- 1917090 TI - Predictability of radiographic diagnosis of variations in root canal anatomy in mandibular incisor and premolar teeth. AB - Four hundred and fifty-five extracted mandibular incisor and 340 extracted mandibular premolar teeth were radiographed to assess the incidence of twin canals as visualized on radiographs taken in the mesio-distal direction. The ability to detect the presence of these twin canals by viewing radiographs taken in the standard bucco-lingual direction was then assessed. Using the guideline that 'disappearance or narrowing infers division' when viewing these radiographs resulted in a failure to diagnose one-third of the twin canals. PMID- 1917091 TI - A method for the construction of simulated root canals in clear resin blocks. AB - A method for the construction of simulated root canals in clear resin blocks is described. The canals are inexpensive, simple to produce and are of high enough quality for use in both undergraduate and continuing education. With minor modifications, the canals can also be used for research, particularly during the assessment of instruments and preparation techniques. PMID- 1917092 TI - A one-stage calcific barrier technique in a root-fractured incisor tooth: a case report. AB - This paper describes the use of calcium hydroxide powder as an immediate plug before root canal obturation in the case of a root-fractured upper central incisor that had been unresponsive to 18 months of treatment to create a calcific barrier. The calcium hydroxide plug allowed both good condensation of the filling material and prevention of extrusion of the root filling material which could have been detrimental to continued healing of the fracture. PMID- 1917093 TI - Endodontics in the UK 1990: an overview. AB - The first workshop on endodontics, in 1978, pointed out that the standard of endodontics in the United Kingdom was poor. The British Endodontic Society has subsequently attempted to improve the remuneration in the NHS by conducting and publishing a survey, and also establishing guidelines for minimum acceptable standards. Despite this, in the author's opinion, there has been no improvement. However, four ways of raising the standards of endodontics are proposed. PMID- 1917094 TI - Undergraduate endodontic teaching at the London Hospital Dental Institute. AB - Integration, whole patient care and small group teaching are concepts which set the pattern for undergraduate teaching at 'The London'. This system promotes co operation between disciplines, enables students to see the basic teaching in a wider clinical context, activates the learning process and gives students an opportunity to learn responsibility by running their own 'mini-practices'. Unfortunately, the system also has some undesirable effects, which are discussed with special reference to the teaching of endodontics. PMID- 1917095 TI - The curriculum in endodontology at the Academic Centre for Dentistry Amsterdam (ACTA), The Netherlands. AB - At the Academic Centre for Dentistry, Amsterdam (ACTA) clinical endodontics is taught and practised in a general clinic supervised by general dental practitioner instructors; they are continuously trained and supported by the endodontics staff, who are members of the Department of Cariology and Endodontology. The scientific basis of endodontology and the theory of clinical endodontic procedures are taught by the endodontic staff, primarily by using a textbook, a clinical manual, videotapes and a computer program, all accompanied by detailed instructional objectives. During their preclinical training, which allows 63 hours for practising procedures and performing several clinical tests, the students are taught one basic technique to prepare and fill root canals and to restore endodontically treated teeth. This technique, accompanied by clearly outlined criteria, is also used in the patient clinic. In the experience of the staff, who are limited to endodontology, the use of manuals, audiovisual aids and instructional objectives has been very beneficial, and the student's assessment of the endodontology course was, in general, very favourable. Although the clinical results are quite good, the endodontic staff feel that there is still some room for improvement of the teaching. Finally, an elective period has recently been introduced. PMID- 1917096 TI - Comparison of undergraduate endodontic teaching programmes in the United Kingdom and in some dental schools in Europe and the United States. AB - The pattern of teaching root canal therapy within dental schools of the UK was determined and compared with that carried out within several dental schools in Europe and the USA. Although it appeared that 'teachers of endodontics' in the UK were advocating techniques adopted elsewhere, it was clear that, within the dental undergraduate curriculum as a whole, the teaching of root canal therapy was given a lower priority than that in some schools in Europe and the USA. Recommendations to remedy this unsatisfactory position are provided. PMID- 1917097 TI - Vocational trainees' views of their undergraduate endodontic training and their vocational training experience. AB - By means of a questionnaire, the views of recently qualified graduates, who were participating in vocational training schemes, on their undergraduate endodontic training and postqualification experience were examined. On the basis of these finding suggestions are made as to what changes are necessary in their undergraduate training and how their skills can be further improved after qualification. PMID- 1917098 TI - The organization and running of postgraduate endodontic 'hands-on' courses. AB - Considerable preparation, planning and detailed organization are necessary if endodontic 'hands-on' courses are to be stimulating and worthwhile for participant and teacher alike. Projection facilities, lighting, seating and working surface requirements must be checked immediately on arrival at the venue. The format, although flexible enough to allow for the wide range of knowledge and practical ability found within any one group, must adhere to and stress the current fundamentals in endodontic teaching. Not only can information and skill in diagnosis, root canal preparation and obturation be taught in a 'hands-on' format, but rubber dam isolation techniques can also be practised very successfully. Tutors must be prepared to demonstrate personally their clinical ability and experience of principles and techniques taught during the course. Post-course feedback can be an extremely useful means of ensuring that 'hands-on' courses are relevant, with the appropriate practical emphasis required by the general dental practitioner, as well as the necessary stress on endodontic principles. PMID- 1917099 TI - Organizing a postgraduate course. AB - The running of a section 63 hands-on course on endodontics requires prior planning. Suggestions on how to plan such course include the design of the programme, the number of course members and instructors, requirements from the postgraduate centre, equipment and materials needed, travel and accommodation, and finally reimbursement. PMID- 1917100 TI - Continuing education in endodontology in The Netherlands. AB - The Netherlands Society for Endodontology has developed a 5-year plan for continuing education that served as a guideline for two basic courses in endodontology. The 2-day basic course has been attended by over 2000 dentists, and has been very much appreciated according to the evaluation outlined in this article. The development and content of these courses are described. Over the past 10 years it has been shown that there is a high demand for continuing education in endodontology in The Netherlands, and that a properly designed and presented course may be very successful. PMID- 1917101 TI - British Endodontic Society proposals for recruitment of instructors for 'hands on' courses for general dental practitioners. AB - This paper addresses the problem of the insufficient number of instructors available for 'hands-on' endodontic courses for dental practitioners throughout the UK. The Council of the British Endodontic Society proposes the setting up of regional endodontic study clubs. Subsequently, some study club members will be encouraged to present 'hands-on' courses to other practitioners in their region. It is hoped that Area Representatives of the Council, who will organize the study clubs, will be found among the university teachers of endodontics. PMID- 1917102 TI - Specialization in endodontics. AB - The dental profession within the UK is currently reviewing the desirability of recognition of practice-based specialties and the establishment of specialist registers in various disciplines, including endodontics. In order to merit consideration for specialty status, in any discipline there must be an increase in the level of theoretical knowledge, and in the range and complexity of clinical procedures beyond the basic level of training. There must be an identified public need extending beyond the provisions of the general dental services for the particular skills of the practice-based specialist, who would also complement the consultant services, which have a limited capacity to provide the level of treatment demanded. Acceptance of the principle of specialist practice implies a belief that this will enhance the development of the profession, improve academic and clinical standards and provide a higher-quality and more widely available service to the public. The case for the specialist endodontist is argued, as is the importance of establishing appropriate academic and clinical training programmes to equip individuals with the requisite knowledge and skills. Academic institutions must develop imaginative and innovative courses to provide such education within the profession. PMID- 1917103 TI - Establishing a postgraduate course in endodontics. AB - A proposal was first made to the University of London in 1985 to establish an MSc degree in Endodontics. It was finally approved in 1988. The first course started in 1988, and is now offered by two schools of the University, the United Medical and Dental Schools of Guy's and St Thomas's Hospitals and the Institute of Dental Surgery. The course has three main components: a taught part, clinical practice and a research project. The taught part is a course common to both the schools, while clinical practice and the research are carried out at the students' respective schools. PMID- 1917104 TI - Setting up an MSc programme in endodontics. AB - The course has been designed to provide a suitable foundation for academic and general practice careers. Emphasis has been placed on developing diagnostic and practical skills. Students are encouraged to review their clinical practice critically in the light of recent advances in knowledge. The course begins with an intensive period of lectures and seminars covering general aspects of endodontics, and is generously supplemented by practical demonstrations and classes on a variety of procedures performed on laboratory models. The course continues with lectures and seminars designed to stimulate group discussion. These are complemented by supervised clinical sessions encompassing assessment, planning and treatment of a comprehensive range of conventional and surgical endodontic problems. The syllabus includes relevant basic sciences, pathology, differential diagnosis, pharmacology and therapeutics. The biological basis for endodontics is stressed and covers the following: maintenance of pulp vitality; effects of pulp capping pulpotomy and pulpectomy; the management and treatment of traumatic injuries to teeth; the management of medically compromised patients; the effect of various methods of instrumentation of root canals; radiology; restorative treatment of the endodontically treated tooth; the interface between endodontics and periodontics, prosthetics or orthodontics. Each student is required to undertake a research project and write a report. PMID- 1917105 TI - IgG4 autoantibodies to DNA in systemic lupus erythematosus patients. AB - The presence of DNA-specific IgG4 antibodies was demonstrated in the sera of patients with systemic lupus erythematosus (SLE) by a microtiter solid-phase radioimmunoassay. A patient with distal interphalangeal swelling and extensive ulcers in the oral cavity, seronegative for anti-DNA antibodies of the IgG isotype, was found to have anti-DNA autoantibodies exclusively of the IgG4 subclass. These autoantibodies directed against the dsDNA conformation cross reacted with chondroitin sulfate, dermatan sulfate and heparin. PMID- 1917106 TI - Differences in level and avidity of secretory IgA antibodies in breast milk of Swedish, Indian and Japanese mothers to soybean protein. AB - Colostrum was collected from Swedish, Indian and Japanese mothers. The samples were as a mean, collected 4.00-4.25 days after delivery of term infants. The level of specific IgA antibody to 2S, 7S and crude soybean antigen were measured by the enzyme-linked immunosorbent assay (ELISA). The avidity of the IgA antibodies to 7S soybean antigen was also measured with an ELISA system using different molarities of potassium thiocyanate for elution of the specific IgA antibody from solid phase-bound antigen. The level of specific IgA antibody to 7S and crude soybean antigen in the milk of the Indian mothers was significantly higher than in the milk of the Japanese mothers (p less than or equal to 0.01). In contrast, the avidity expressed as the molarity of KSCN for 50% elution of IgA antibody to 7S soybean antigen in the milk of the Japanese mothers was significantly higher than in the milk of the Indian mothers (p less than 0.01). PMID- 1917107 TI - A new method of the measurement of nasal secretion in guinea pigs. AB - A simple quantitative method to measure nasal secretion in guinea pigs is described. Nasal secretion was measured with a piece of cotton thread dyed with fluorescein at one end which was inserted into an anterior naris and kept there for 60 s. The stretch of color of a thread dyed with fluorescein was proportional to fluid volume and to increase in weight of a thread due to absorbed nasal secretion induced by nasal provocation. In addition, the stretch of color due to nasal secretion was associated with the score of rhinorrhea. Thus, it is considered that the amount of nasal secretion can be reflected to the length of the stretch of color. Each secretion on the ipsilateral and the contralateral sides induced by nasal provocation could be separately measured by this method. The amount of nasal secretion induced by allergen in passively sensitized guinea pigs could be reduced by pretreatment with ketotifen or flutropium. These results suggest that our method may serve as a quantitative test for nasal secretion in guinea pigs, which would be useful in the study of hypersecretory response in the allergic model or in evaluating the effect of antiallergic drugs on nasal allergy. PMID- 1917108 TI - Depolarizing action of allergens on passive sensitized lymphocytes. AB - An ability of rat thymus lymphocytes to respond to pollen allergens has been found. The lymphocytes were exposed with plasma of pollinosis patients. The subsequent addition of allergens specific for the patient caused the decrease of lymphocyte plasma membrane potential. The decrease was detected by use of potential-sensitive fluorescent probe 4-(p-dimethylaminostyryl)-1 methylpyridinium. This newly found effect can be employed for diagnostics of atopic states. PMID- 1917109 TI - Ongoing IgE synthesis by atopic B cells is enhanced by interleukin-3 and suppressed directly by interferon-gamma in vitro. AB - Human recombinant interleukin-3 (rIL-3; 10 U/ml) consistently augmented spontaneous IgE synthesis by isolated atopic B cells in vitro, whereas rIL-4 (1 1,000 U/ml) failed to induce IgE synthesis by these cells. Recombinant interferon gamma (rIFN-gamma) suppressed ongoing IgE production by atopic B cells in a dose dependent manner. IFN-gamma also inhibited IgE synthesis by a human myeloma cell line (U-266), demonstrating the direct effect of IFN-gamma on the terminal differentiation of IgE-secreting plasma cells. IL-3 and IFN-gamma from different sources displayed the same effects on IgE synthesis. Neutralizing antibodies toward IL-3 or IFN-gamma abolished their activities toward IgE synthesis, supporting the specificity of the effect of these cytokines. The quantity of endogenous IFN-gamma produced by stimulated T cells was significantly decreased in atopic patients compared to nonatopic controls, which might be responsible for the propensity of a high blood IgE level in atopic patients. PMID- 1917110 TI - Identification of soybean proteins responsible for respiratory allergies. AB - Serum samples from 32 patients who suffered attacks during the asthma outbreaks of 1987 and 1988 in Cartagena, Spain, supposedly caused by soybean dust, were studied. At least 90% had specific IgE to shell components and only 13% showed specific IgE to shell-depleted soybean grains. A control group of 32 patients who also suffered asthma attacks but on different days from those of the outbreaks were negative. The shell's most important allergen with an apparent molecular weight of 8 kDa was not present in shell-depleted grains. This allergen as well as other less important shell allergens may be different from the allergens already identified by using serum from patients suffering food allergy to soya. PMID- 1917111 TI - Peripheral denervation suppresses the late phase of delayed-type hypersensitivity. AB - The impact of peripheral denervation on antigen-specific immune responses was analysed on the B and T cell levels. Delayed-type hypersensitivity (DTH) response to sheep red blood cells (SRBC) or oxazolone was used in mice as a model system of in vivo T cell reactivity. Serum antibody levels to SRBC, measured by an enzyme-linked immunosorbent assay (ELISA), were evaluated to analyse the B cell response. The effect of peripheral denervation on immune responsiveness was studied both at the point of sensitization and elicitation. The results show that peripheral denervation significantly suppresses the local DTH response. The late, inflammatory phase but not the early phase of the DTH reaction was reduced after denervation (p less than 0.01). The DTH suppression by denervation was similar irrespective of whether the neurectomy was performed 1 or 4 weeks prior to sensitisation. Even in the contralateral limb, with intact innervation, the inflammatory DTH reactivity was decreased. We believe that this phenomenon might be due to abrogation of the reflex arch since the denervation procedure did not give rise to a significant systemic downregulation of DTH. Also, peripheral denervation significantly suppressed footpad swelling induced by local administration of cholera toxin, a potent phlogistic compound. The antibody response against the same immunogen was not influenced by denervation. Our results suggest that denervation of a mixed peripheral sensory/motor nerve abrogates the formation of both T cell-dependent and independent inflammatory responses. PMID- 1917112 TI - IgG Fc receptors on epithelial cells of distal tubuli and on endothelial cells in human kidney. AB - IgG Fc receptors (FcR) in cryostat sections of human kidney were studied using functional assays and monoclonal antibodies (MoAbs). Using functional assays, FcR were detected on cells in glomeruli and distal convoluted tubuli, on endothelial cells and on interstitial cells. These cells were also stained with B1D6, a MoAb reactive with a 40-kD molecule with low affinity FcR activity. Using MoAbs against leukocyte FcR, a different pattern of reactivity was obtained. MoAbs against FcR I (32.2), FcR II (IV.3 and C1KM5) and FcR III (3G8 and Leu11b) stained interstitial macrophages only. The data confirm the presence of FcR on renal glomeruli and interstitial cells and also indicate that epithelial cells of distal tubuli and endothelial cells express FcR. Furthermore, renal FcR appear to be structurally different from the FcR I, II and III defined on leukocytes. PMID- 1917113 TI - Inhalation exposure of mice to trimellitic anhydride induces both IgG and IgE anti-hapten antibody. AB - The development of antibody responses resulting from inhalation exposure to chemical allergens has been studied in mice. Inhalation exposure of BALB/c mice to atmospheres containing approximately 5 mg/m3 of the respiratory allergen trimellitic anhydride (TMA) resulted in the appearance of both serum IgG and IgE anti-hapten antibody. IgE anti-TMA was first detectable 2-3 weeks following the initiation of exposure and was still present at 6 weeks. Under the same conditions of exposure, 2,4-dinitrochlorobenzene (DNCB), a contact allergen which apparently lacks the capacity for respiratory sensitization, failed to elicit detectable amounts of anti-dinitrophenol (DNP) antibody. Exposure to increased concentrations of atmospheric DNCB (15 mg/m3) did, however, result in an IgG anti DNP response but not in IgE antibody. These data demonstrate firstly, that atmospheres containing low molecular weight respiratory allergens can initiate specific IgE responses in mice, and secondly, that inhaled chemicals may differ in their ability to induce IgE antibody. PMID- 1917114 TI - IgE-positive duodenal mast cells in patients with food-related diarrhea. AB - Thirty-seven consecutive adult patients with a history of adverse reactions to foods, manifested mainly as diarrhea, were investigated with skin prick test (SPT), IgE levels in serum, and the presence of IgE bound to mast cells in duodenal biopsy specimens. Nineteen percent had increased serum IgE levels indicating the presence of atopic disease and in 35% positive SPTs for one or several allergens related to their gastrointestinal symptoms were found. In 92% of the patients with positive SPTs to food, IgE-positive mast cells in duodenal biopsy specimens were found, twice as many as in patients with negative SPTs (47%). Forty-two percent of normal individuals without any adverse reactions to foods had IgE-bearing mast cells in their intestinal mucosa. The results showed that 'arming' of mast cells with IgE locally was relatively prominent but not consistent in the gut of patients with food-related diarrhea suggested to be allergic by positive SPT. Intestinal IgE-mediated hypersensitivity reactions could be of pathogenetic significance in most of these patients. However, since also half of the normal individuals were found to have IgE-positive intestinal mast cells, this phenomenon presumably also reflects a normal physiological defence mechanism. PMID- 1917115 TI - The effect of systemic treatment with platelet-activating factor on the migration of eosinophils to lung, pleural and peritoneal cavities in the guinea pig. AB - Subcutaneous treatment of guinea pigs with platelet-activating factor (PAF) caused an increase in the prevalence of eosinophils in lavage fluid recovered from pulmonary airways, and pleural and peritoneal cavities. In PAF-treated animals, total numbers of eosinophils and macrophages in washings were positively correlated, thus there was no apparent competition between the two cell types for migration at traffic sites into body cavities. The results indicate that PAF acts centrally to enhance the migration of eosinophils and monocytes into body cavities, perhaps by inducing bone marrow release of both classes of leucocytes which may then migrate constitutively into lung, pleural and peritoneal cavities. PMID- 1917116 TI - Reminiscing: the state of the art as a basis for practice. AB - This integrated review presents the state of the art in reminiscing and life review as derived from a review of the literature from 1960-1990. Reports, reviews, and research are categorized and critiqued with the purpose of clarifying the use of reminiscing for practice. Out of ninety-seven published articles describing reminiscing, only seven report negative outcomes; the remainder are either positive or nonevaluative. As a result, the author concludes that clinicians should use reminiscing in their practice, and researchers should continue to define the variables that lead to successful reminiscing. PMID- 1917117 TI - Ethnicity and intergenerational perceptions of family solidarity. AB - Intergenerational interaction between matched pairs of older parents and their middle-aged offspring were explored in this research, comparing Mennonites and non-Mennonites. Middle-aged respondents replied to a mailed questionnaire, and their parents were interviewed. Five dimensions of family solidarity were compared between the generations, with the result that middle-aged offspring typically report less family solidarity than do their parents. These results are explained in terms of the concept of the "developmental stake." PMID- 1917118 TI - Experience sampling with elderly persons: an exploration of the method. AB - The daily lives of a sample of elderly widows (greater than 69 years of age) were studied using the method of experience sampling developed by Csikszentmihalyi and his colleagues. The purpose of the study was to investigate the response of elderly people to experience sampling as a means of collecting information about their activities, thoughts, and moods during the course of one week. The method proved acceptable to the majority of participants and yielded reliable, valid data about their home lives, particularly from among the younger, more physically able women. Experience sampling was, within certain limits, a useful method of obtaining information from elderly people. PMID- 1917119 TI - Identity processes and perceptions of the life span in chronic mental patients. AB - This study was an exploratory investigation of identity and life-span perceptions in a sample of thirty-seven chronic mental patients, ranging from twenty-three to sixty-four years of age, using the "life drawing," a projective technique. Age differences were found in the adaptation of identity to the life experiences associated with mental illness. Individuals less than thirty years old were more likely to adopt a "patient identity"; in contrast, the over-forty years-old adapted to their illness through denial. These differences held regardless of psychiatric diagnosis, suggesting a process of identity adaptation more general than is implied in mental disorder diagnostic systems. PMID- 1917120 TI - No time to look back: approaching the finish line of life's course. AB - Gerontologists have labelled individuals who do not follow the normal aging pattern of reduced physical activity and declining health as "successfully aging" adults. Competitive and sport-involved elder persons represent a kind of elderly elite who may exhibit special psychological characteristics that help to explain their active approach to late life. As part of a larger study on the physical fitness and body composition of participants at seniors' games, a qualitative exploration of personal life philosophy was undertaken in order to initiate understanding about the cognitive make-up of competitive older men and women. Content analysis of open-ended survey questions about life in review and future goals permitted insight into life orientation differences between men and women. The responses provided evidence that sport and physical recreation may be an important type of coping strategy for some elderly adults who find life meaning and a sense of achievement in challenging themselves physically. Beyond a general optimism in life orientation, uncertainties about the nature of the future left many with a sense of urgency combined with specific short-term goal setting. PMID- 1917121 TI - Weather fronts and acute myocardial infarction. AB - Some methodological aspects are discussed of the investigation of acute infarct myocarditis (AIM) in relation to weather fronts. Results of a new method of analysis are given. Data were analysed from about the hour of the onset of symptoms, and led to the diagnosis of AIM either immediately or within a few hours or days (3019 cases observed over 4.5 years during 1982-1986 in Plzen, Czechoslovakia). Weather classification was based on three factors (the type of the foregoing front, the type of the subsequent front, the time section of the time interval demarcated by the passage of the surfaces of the fronts). AIM occurrence increased in particular types of weather fronts: (i) by 30% during 7 12 h after a warm front, if the time span between fronts exceeded 24 h; (ii) by 10% in time at least 36 h distant from the foregoing cold or occlusion front and from the succeeding warm or occlusion front; (iii) by 20% during 0-2 h before the passage of the front, provided the foregoing front was not warm and the interval between fronts exceeded 5 h. AIM occurrence decreased by 15%-20% for time span between fronts greater than 24 h at times 6-11, 6-23 and 6-35 h before a coming warm or occlusion front (for interfrontal intervals 25-48, 49-72 and possibly greater than 72 h), and also at 12-23 and possibly 12-35 h before a cold front (for intervals 49-72 and possibly greater than 72 h), if the foregoing front was cold or an occlusion front. PMID- 1917122 TI - Dynamic sweating response of man to infrared irradiation in various spectral regions. AB - In an attempt to detect differences in the thermal effect of infrared irradiation of different wave-lengths, transient sweating response to infrared irradiation in various spectral regions was examined. In Series 1, the ventral or dorsal surface of the nude subject was irradiated repetitively for a period of 4 min (2 min on, 2 min off) by each of three kinds of infrared heaters with main emissivity in 'near-infrared' (NIR; 0.7-2.8 microns), 'intermediate-infrared' (MIR; 1.5-5.8 microns), and 'far-infrared' (FIR; 2.8-25 microns) regions. The sweating response on a non-irradiated area tended to be the greatest with MIR, while the magnitude of the sweating response on the irradiated area showed no consistent differences among various wavelengths. The results infer that MIR stimulated cutaneous thomoreceptors most effectively, while its direct effect on local sweat gland activity was minimal. In Series 2, the effects of 9-12 min irradiations in more restricted ranges of wavelength were compared by the combination of the three kinds of heaters with filters (translucent to wavelength ranges of 1.3-2.7, 2.7 3.5, 3.6-8.0 microns, respectively). The sweating response on a remote area was predominantly greater with the range of 2.7-3.5 microns than with the other wavelength ranges, while the local effect on sweating was minimal with this range. The results of Series 2 reinforce those of Series 1, indicating that the degree of stimulation of cutaneous thermoreceptors and of direct thermal effect on sweat gland activity differ with spectral regions incident on the skin, thus affecting local and remote effects on the sweating response. PMID- 1917123 TI - Air temperature and humidity and human comfort index of some city parks of Mexico City. AB - A series of air temperature (Ta) and relative humidity (HR) measurements were carried out in five urban parks and their surroundings in Mexico City. It was found that Ta is lower and RH is higher inside the parks. There were differences (P less than 0.05) between the parks and surroundings in air temperature, relative humidity, vapour pressure (e), vapour pressure deficit (VPD) and the thermohygrometric human comfort index (THI). Ta differences were more marked during the early afternoon. Maximum differences of Ta, e, and DPV were 5.6 degrees C, 0.6 and 1.2 mbar. There is strong evidence that the magnitude of differences in Ta are directly proportional to the surface of urban parks. PMID- 1917124 TI - Estimation of cold stress effect on dairy cows. AB - Twelve crossbred heifers (Slovak Spotted x Holstein-Friesian) were housed in an open, uninsulated barn with straw bedding and a concrete-floored yard. Minimum temperatures inside the barn were as low as -19 degrees C. The average milk yield decreased as the temperatures approached these minima. Compared with the temperature conditions, the feed intake and blood levels of glucose and free fatty acids increased. The level of sodium declined significantly during the second cold period. Correlations and regressions between milk yield and biochemical parameters were calculated, and the results indicate that the concentrations of free fatty acids, cholesterol, and triiodothyronine and the haematocrit values may serve to predict milk production during periods of cold stress, or in lactations of 305 days. PMID- 1917125 TI - An eleven-year cycle in human births. AB - The prominent endogenous cycle of the sun, with a period of approximately 11 years, is correlated with human conceptions. Time series methods (periodograms and periodic regression analyses) established that an approximate 11-year period exists in the data on births in the 20th century (1909-1985) in the United States and in New Zealand. Statistical comparisons indicated a reliable and direct relationship of conceptions with the approximately 11-year sunspot cycle. These findings were discussed in terms of the possible mediating role of geomagnetic disturbances and other factors that have been suggested in the literature to mediate human conception. PMID- 1917126 TI - Sensible climates in monsoon Asia. AB - This study identifies characteristics of the geographical distribution of sensible climates and their diurnal and annual variations, and presents a classification of bioclimates in monsoon Asia by using Kawamura's discomfort index formula. During the hottest month, tropical areas and areas in central and South China are uncomfortable for humans throughout the day and night, and temperate zones in lowlands are uncomfortable during the daytime. Tropical zones are uncomfortable all year long and temperate zones in lowlands are uncomfortable during summer. Four climatic types were distinguished in monsoon Asia. Climatic type I, hyperthermal throughout the year, occurs in the tropics south of latitude 20 degrees N. Climatic type II, hyperthermal in the hottest month and comfortable in the coldest month, extends over latitudes from 20 degrees to 30 degrees N except in the highlands. Climatic type III, hyperthermal in the hottest month and hypothermal in the coldest month, encompasses temperate zones of East Asia and subtropical arid areas of northwestern India. Climatic type V, comfortable in the hottest month and hypothermal in coldest month, occurs near the southeast coast of the Soviet Union and in the highlands of the Himalayas. PMID- 1917127 TI - The spectral distribution of biologically active solar radiation at Miami, Florida, USA. AB - The spectral distribution of solar radiation was studied under different sky conditions during a 15-month period in Miami, Florida (USA), and over a latitudinal gradient at solar maximum. Spectroradiometric scans were characterized for total irradiance (300-3000 nm) and the relative energetic and photon contributions of the following wavelength regions: UV-B (300-320 nm); UV-A (320-400 nm); B (400-500 nm); PAR (400-700 nm); R (600-700 nm); and FR (728-732 nm). Notable results include: (i) significantly higher UV-A energy fluxes than currently in use for laboratory experiments involving the biological effects of this bandwidth (values ranged from 33.6 to 55.4 W/m2 in Miami over the year); (ii) marked diurnal shifts in B:R and R:FR, with elevated R:FR values in early morning: (iii) a strong correlation between R:FR and atmospheric water content; and (iv) unusually high PAR values under direct sunlight with cloudy skies (2484 mumol/2 per s). PMID- 1917128 TI - Hospital cardiovascular deaths and total distribution of deaths in 180 consecutive months with different cosmic physical activity: a correlative study (1974-1988). AB - The dynamics of total hospital deaths from different kinds of cardiovascular diseases in one 1000-bed hospital were compared with 10 monthly cosmic/solar and geomagnetic physical activity parameters. Data used were of 180 consecutive months; 15,601 deaths including 5667 from cardiovascular diseases were included in this study. It was concluded that the number of monthly hospital deaths shows a highly significant correlation with monthly solar physical activity. PMID- 1917129 TI - The receptor encoded by the human c-MET oncogene is expressed in hepatocytes, epithelial cells and solid tumors. AB - The human c-MET oncogene encodes a transmembrane tyrosine kinase (p190c-met) with structural and functional features of a growth-factor receptor. Monoclonal antibodies (MAbs) have been used to investigate the distribution of the c-Met protein in human normal and neoplastic tissues. By immunofluorescence microscopy homogeneous expression was detected in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Positive staining was also found in epithelial cells of the endometrium and ovary, and in basal keratinocytes of esophagus and skin. By Northern blot analysis, high levels of c-met messenger RNA were detected in specimens of liver, gastro-intestinal tract and kidney. c-met-specific mRNA was also found in thyroid, pancreas and placenta, in which organs c-Met protein was barely detectable by immunofluorescence. The antibodies revealed expression of c-MET protein in hepatomas (11/14), carcinomas of colon and rectum (19/21), stomach (11/22), kidney (16/19), ovary (9/17) and skin (7/17). Carcinomas of the lung (13/20), thyroid (11/13) and pancreas (5/7) were also positive. In these last cases (lung, thyroid and pancreas) tumor cells were homogeneously stained by the antibodies, whereas in their normal counterparts staining was barely detectable. These data suggest that the receptor encoded by c-MET plays a physiological role in epithelial cell growth and that its expression is altered in human carcinomas. PMID- 1917130 TI - Changes in glycolipids in human renal-cell carcinoma and their clinical significance. AB - The expression patterns of glycolipids of human renal-cell carcinoma were studied in primary tumors from 23 cases and 5 metastatic lesions from 4 cases using HPTLC (high-performance thin-layer chromatography). The expression pattern of glycolipids in primary tumors was characteristic of the histological cell type. In granular-cell carcinoma, lactosylceramide (CDH), GM3 and the longer-chain gangliosides (gangliosides migrating more slowly than GM3) increased, although in clear-cell carcinoma, CDH and other glycolipids tended to decrease. Globoside decreased in all cases but one, irrespective of cell type. In metastatic lesions of the clear-cell type, the prominent increase in longer-chain gangliosides was characteristic. Furthermore, the same expression pattern as that of metastastatic lesions was shown in 3 of 14 patients with primary clear-cell carcinoma, all of whom developed metastases soon after radical nephrectomy. These studies indicate that the increased expression of the longer-chain gangliosides in primary tumor is one of the factors associated with high metastatic potential, and also predict early post-operative development of metastasis. PMID- 1917131 TI - Cysteine endopeptidase activity levels in normal human tissues, colorectal adenomas and carcinomas. AB - We have assayed cysteine endopeptidase activities in 17 types of normal human tissue and in matched sets of colorectal mucosa, adenoma and carcinoma samples. Our data indicate that cathepsin B enzyme levels vary 70-fold and cathepsin L enzyme levels vary 20-fold from one normal tissue to another. Cathepsin B specific activity in normal tissues fell into 3 categories. High activity, with a mean of 156.7 +/- 41.5 nmoles min-1 mg-1 protein, was measured in liver, thyroid, kidney and spleen; intermediate activity, with a mean of 60.2 +/- 8.3 nmoles min 1 mg-1 protein, was measured in heart, colon, adrenal and lung; and low activity, with a mean of 18.4 +/- 9.7 nmoles min-1 mg-1 protein, was measured in prostate, testis, nerve, stomach, pancreas, brain, skeletal muscle, skin and breast. Cathepsin L specific activity fell into 2 categories. High activity, with a mean of 51.1 +/- 4.9 nmoles min-1 mg-1 protein, was measured in thyroid, liver and kidney; and low activity, with a mean of 11.4 +/- 5.5 nmoles min-1 mg-1 protein, was measured in spleen, colon, heart, adrenal, lung, testis, brain, nerve, skin, stomach, pancreas, skeletal muscle, prostate and breast. Our characterization of these enzyme levels provides a reference standard for normal cathepsin B and L activities in human tissues that should enhance the detection of their deregulation in disease states. For example, in studies of colorectal carcinoma and normal mucosa, we observed a significant tumor-specific increase in cathepsin B and L activities with particularly high activity levels in earlier (Dukes' A and B) compared to later (Dukes' C and D) stages of colorectal cancer. In contrast, adenomas from colorectal cancer patients expressed normal levels of cathepsin B activity, providing evidence that the increase in expression of cathepsin B may be a sensitive marker for progression from the pre-malignant to the malignant state in the development of colorectal cancer. PMID- 1917132 TI - Expression of integrin receptors on 45 clinical neuroblastoma specimens. AB - Immunohistological expression of integrins has been analyzed on 45 neuroblastoma specimens representative of the different clinical and histological forms of the tumor. None of the specimens expressed the alpha 5 chain of the integrins. The beta 1 chain was expressed on all specimens, the alpha 1 chain on 44 specimens and the alpha 3 chain on 42; the 4 specimens which lacked alpha 1 or alpha 3 were stage-4 neuroblastomas. The alpha 2 chain was expressed on 18 specimens, and the alpha 6 chain on 17; 15 reacted with both. Their reactivity was related to the maturation of the tumor rather than the stage of the disease: they were expressed on low-grade, well-differentiated specimens; stage 3-4 neuroblastoma specimens analyzed at diagnosis were negative, but usually expressed both chains when analyzed after in vivo differentiation by chemotherapy. alpha v reacted with 18 specimens and beta 3 with 12, without strict relation with the stage of the disease and/or its degree of differentiation; 9 well-differentiated specimens expressed the beta 4 chain; only 4 well-differentiated specimens expressed the alpha 4 chain. The 4 specimens which lacked alpha 1-beta 1 or alpha 3-beta 1 expression had n-myc amplification, whereas those which expressed either alpha 4, beta 4, beta 3 or alpha v had no amplification. Furthermore, the expression of the 3 heterodimers alpha 4-beta 1, alpha v-beta 3 and alpha 6-beta 4 was essentially observed on primary tumors which developed in the mediastinum. The expression of alpha 2-beta 1 and alpha 6-beta 1 was observed on both n-myc positive and -negative specimens. beta 1 and alpha 3 were diffusely expressed on all counterparts of these tumors, from undifferentiated neuroblasts to ganglion and Schwann cells. The alpha 1 chain reacted with undifferentiated and intermediate neuroblasts as well as with Schwann cells, but ganglion cells were negative. alpha 2 and alpha 6 chains were negative on undifferentiated neuroblasts, variably expressed on intermediate neuroblasts, and restricted to Schwann cells in ganglioneuroma. The expression of alpha 4 and beta 4 was restricted to Schwann cells. alpha v and beta 3 occasionally reacted with undifferentiated and intermediate neuroblasts; alpha v was strongly positive on Schwann cells but negative on ganglion cells, whereas beta 3 was positive on both neuronal and non-neuronal populations. PMID- 1917133 TI - Effects of HC antibody in autologous tumor-specific cytotoxicity by human melanoma tumor-infiltrating lymphocytes. AB - Heteroconjugate (HC) antibody has a potential use in cancer biotherapy because of its ability to mimic antigenic specificity and induce cytotoxicity in the activated lymphocytes against various tumor cells. This study investigated the effects of HC antibody (anti-CD3 MAb x anti-p97 melanoma cell MAb) in autologous tumor-specific cytotoxicity by interleukin-2 (IL-2)-activated melanoma tumor infiltrating lymphocytes (TILs). HC antibody significantly augmented p97pos uncultured autologous tumor cell lysis mediated by effector TILs or cytotoxic T lymphocyte (CTL) clones derived from TIL. It did not significantly increase p97mix autologous tumor-cell lysis and slightly inhibited the lysis only at higher E:T ratios and higher concentrations (greater than or equal to 100 ng/ml). It inhibited p97neg autologous tumor-cell lysis. HC antibody respectively induced potent lysis of p97pos or modest lysis of p97mix tumor cells by allogeneic effector TILs as well as PBMC. In contrast, parental anti-CD3 MAb primarily suppressed the autologous tumor-specific cytotoxicity, and did not induce lysis of uncultured melanoma cells, regardless of differences in expression of p97 antigens on tumor cells. Although parental anti-p97 MAb did not augment or suppress the autologous tumor-specific cytotoxicity, it completely abrogated HC antibody-mediated augmentation of p97pos autologous tumor cell lysis by effector TILs. Anti-class-I MAb, but not anti-DR MAb, suppressed the autologous tumor specific cytotoxicity, but failed to block HC antibody-mediated augmentation of p97pos autologous tumor-cell lysis. These results suggest that the levels of p97 antigen expression largely influenced HC antibody-mediated modulation of TIL cytotoxicity against uncultured autologous tumor cells. PMID- 1917134 TI - Incidence of histologic types of uterine sarcoma in relation to menstrual and reproductive history. AB - To determine whether the occurrence of one or more histologic types of uterine sarcoma is related to events in a woman's reproductive life, a population-based case-control study was conducted. One-hundred sixty-seven women newly diagnosed with uterine sarcoma among residents of 6 geographic regions were compared to 208 women selected at random from the same populations with regard to histories of menstruation, pregnancy and childbearing, and breast feeding, as reported during a telephone interview. Compared to women whose menstrual periods began at age 13, women whose menses began earlier were at increased risk of leiomyosarcoma (OR = 2.0, 95% CI 0.9, 4.3); other histologic types were less strongly associated with early age at menarche. Women with leiomyosarcoma and endometrial stromal sarcoma, but not malignant mixed Mullerian tumors, tended to have ceased menstruating 2-3 years later than controls. None of the histologic types was clearly related to parity or to age at first live birth, but each was inversely related to age at last live birth. Associations were observed between leiomyosarcoma and histories of an induced abortion (OR = 4.2, 95% CI 1.2, 14.2) and of breast feeding after a live birth (OR = 0.5, 95% CI 0.3, 1.0); these relationships were not observed for other morphologic variants. These results suggest possible similarities and differences in menstrual and reproductive risk factors among histologic types of uterine sarcoma, and between these malignancies and the more common breast, endometrial and ovarian carcinomas. PMID- 1917135 TI - Prevalence of HTLV-I and HTLV-II infection in Gabon, Africa: comparison of the serological and PCR results. AB - A cluster sampling survey was performed in 1989 in Libreville, Gabon, to determine HTLV-I and HTLV-II prevalence and to compare the efficacy of polymerase chain reaction (PCR) and serology in detecting HTLV-I and HTLV-II infections. A total of 322 sera from adults were tested by ELISA and by Western blot (WB). The WB patterns were interpreted according to WHO criteria and those of the manufacturer. PCR analysis using primer pairs in the gag and pol region, with a specific probe for HTLV-I and HTLV-II, was performed on the lymphocytes of the 322 adults. In addition, 134/322 samples were re-tested with tax primers, in a second laboratory. Using WHO criteria, 8/322 (2.5%) samples were positive on WB and 25 were indeterminate; with the criteria of the kit, 26/322 (8.1%) were positive and 7 were indeterminate by WB. By PCR, 13 (4%) samples were positive, including 12 for HTLV-I (3.7%) and one for HTLV-II (0.3%). All 8 seropositive samples (by the WHO criteria) were positive by PCR, as were 4 out of 25 indeterminate samples. Only one out of 289 seronegative samples was positive by PCR. In contrast, only 12/26 positive samples by the kit criteria were confirmed by PCR. These results confirm the relatively high HTLV-I/II seroprevalence observed in Gabon. HTLV-I infection is preponderant, but HTLV-II is also present. The WHO criteria for WB give a better fit with PCR results than the kit criteria for WB. In the absence of a specific confirmatory test and based on the uncommon "seronegative" HTLV-I/II infection, the indication for PCR appears limited to the positive WB samples (to differentiate HTLV-I and II infection) and to the indeterminate WB samples. PMID- 1917136 TI - Effect of cigarette smoking and alcohol consumption in the etiology of cancers of the digestive tract. AB - This study presents the comparative patterns of risk of selected digestive tract cancers (esophagus, stomach, colon, rectum and liver) for males in relation to cigarette smoking and alcohol drinking, based on the data from case-control studies conducted in the Korea Cancer Center Hospital (KCCH). There was strong positive association between cigarette smoking and esophageal cancer, but none of the other sites was significantly related to cigarette smoking. In esophageal cancer, a dose-dependent effect for cigarette smoking was observed, with the odds ratio ranging from 1.29 for ever smoking up to 1 pack daily to 3.17 for smokers of more than 2 packs per day. The risk declined markedly following cessation of smoking. Cancers of the esophagus, rectum and liver were strongly related to alcohol consumption. Compared with non-drinkers, the OR for heavy drinkers was 9.14 in esophageal cancer, 4.75 in rectal cancer and 2.46 in liver cancer. In cancer of the stomach and colon, however, there was no association with alcohol drinking. PMID- 1917137 TI - Expression of lymphocyte homing receptor gene is lost in multi-drug-resistant variants of human T-lymphoblastoid CCRF-CEM cells. AB - The 2.2-kb human cDNA clone PBL32, encoding for the lymphocyte homing receptor (LHR) was used to study the expression of this determinant in multi-drug resistant (MDR) variants of human T-lymphoblastoid CCRF-CEM (CEM) cells. LHR is significantly associated with the drug-sensitive phenotype, its expression being progressively and quantitatively reduced in MDR variants of CEM cells according to the extent of drug resistance. PMID- 1917138 TI - Autocrine control of human meningioma proliferation: secretion of platelet derived growth-factor-like molecules. AB - We have used cell-culture techniques to investigate growth-factor production by human meningioma cells. Meningioma tissue was dispersed with collagenase and the cells grown to high density in tissue-culture flasks. The cultures were used to generate conditioned medium (MEN-CM), which was used to cultivate IMR32 cells (a human neuroblastoma line) and freshly dispersed primary meningioma cells. MEN-CM profoundly stimulated the in vitro growth of both IMR32 and meningioma cells. In addition, H3-thymidine uptake by cultured meningioma cells was increased in a dose-dependent manner by varying concentrations of MEN-CM. A neutralizing anti body against platelet-derived growth factor (PDGF) completely abolished the stimulatory effects of MEN-CM, whereas an antibody against TGF-alpha was without effect. The mitogenic activity of MEN-CM, as assayed by promotion of H3-thymidine uptake by cultured meningioma cells, eluted from a Sephadex G-100 column in 3 peaks corresponding to molecular weights of greater than or equal to 150, 56 and 28 kDa. Our results show that proliferation of human meningiomas may be under autocrine control via secretion of PDGF-like molecules. PMID- 1917139 TI - Re-transformation of non-transformed hybrids between c-myc-activating mouse plasmacytoma cells and normal fibroblasts by transfection with activated c-Ha-ras but not c-myc. AB - In a mouse plasmacytoma S194, c-myc oncogene is rearranged with Ig gene by chromosomal translocation and is consequently activated. We previously reported that transformation of phenotype and expression of rearranged c-myc were repressed in independently isolated hybrid clones, I-1 and IV-10, between S194 and normal fibroblasts. In order to investigate the relationship between transformation of phenotype and oncogene expression, transcriptionally enhanced c myc or activated c-Ha-ras was transfected into I-1 or IV-10I, a subclone of IV 10. Transfectants expressing high levels of c-myc were found to retain the non transformed phenotypes. On the other hand, transfectants expressing activated c Ha-ras showed the transformed phenotypes. These results suggest that enhanced expression of c-myc is not sufficient for re-transformation of the non transformed hybrid clones between c-myc-activating plasmacytoma cells and normal fibroblasts, but expression of activated c-Ha-ras could diminish or overcome the tumor-suppressive activity of normal fibroblasts. PMID- 1917140 TI - Increased ether lipid cytotoxicity by reducing membrane cholesterol content. AB - Ether-linked glycerophospholipids (ether lipids, EL) are selectively toxic and anti-proliferative agents against cancer cells in vitro. The reason for such selectivity is not completely clear. Their mechanism of action is mediated through an interaction with the plasma membrane and the membrane lipid composition may modulate it. As a continuation of previous reports, we now present data showing that cholesterol concentration modulates EL toxicity in the K562, U937 and MOLT4 leukemic cell lines in vitro. Cells become sensitive to otherwise ineffective doses of EL when their cholesterol content is lowered. Cell cholesterol levels were reduced by exposure to an egg lipid mixture (neutral glycerides, phosphatidylcholine and phosphatidylethanolamine, AL721). The data contribute to an understanding of the EL mechanism of action on membranes and suggest that the cellular cholesterol concentration must be considered a major factor in modulating the cytotoxic effects of EL. PMID- 1917141 TI - Anti-tumoral activity of L and D isomers of aspartic acid beta-hydroxamate on L5178Y leukemia. AB - D and L isomers of aspartic acid beta-hydroxamate (respectively DAH and LAH) were compared for their in vitro and in vivo activity against the murine leukemia L5178Y and their tolerance in vivo in DBA/2 mice. DAH and LAH displayed comparable cytotoxic activity against L5178Y leukemia in vitro. Death of leukemia cells was observed at concentrations above 1.2 mM for both DAH and LAH. High concentrations of L-asparagine partially reversed the growth-inhibitory effects of DAH and LAH on L5178Y cells for concentrations of DAH and LAH lower than 0.6 mM. Intraperitoneal administration of DAH and LAH to mice showed that the LD10, LD50 and LD90 of DAH was 3- to 4-fold greater for DAH than for LAH. DAH was able to eradicate L5178Y tumors in mice without inducing toxic deaths, whereas LAH at comparable doses killed all the animals treated. PMID- 1917142 TI - Establishment of a new human cancer cell line secreting protease nexin-II/amyloid beta protein precursor derived from squamous-cell carcinoma of lung. AB - A new cell line (LC-1/sq) of human lung squamous-cell carcinoma was established from a surgically resected specimen of primary lung cancer. Upon continuous propagation in serum-free culture medium, it secreted trypsin inhibitors into the conditioned medium. The major fraction of the trypsin inhibitor (T1-1) was purified to apparent homogeneity by anion-exchange and gel-filtration high performance liquid chromatography (HPLC) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by transblotting to Immobilon. T1-1 effectively inhibited trypsin. Chymotrypsin, plasmin and kallikrein were inhibited to a lesser extent, but urokinase-type plasminogen activator, elastase, thrombin and papain were not inhibited. The activity of T1-1 was acid-stable and heat-resistant, and its molecular weight was 115 kDa by SDS PAGE. It exhibited single NH2-terminal sequence, and its first 20 NH2-terminal amino-acid residues were identical with those of protease nexin-II (PN II)/amyloid beta-protein precursor (APP). These characteristics of T1-1 suggest that the major trypsin inhibitor secreted by LC-1/sq is indistinguishable from PN II/APP. LC-1/sq is the first lung squamous carcinoma cell line that secretes functionally active trypsin inhibitor, PN-II/APP, in vitro and is useful for studying its biological significance in malignant tumor. PMID- 1917143 TI - Immunotoxins constructed with anti-CD25 monoclonal antibodies and deglycosylated ricin A-chain have potent anti-tumour effects against human Hodgkin cells in vitro and solid Hodgkin tumours in mice. AB - Twenty-three monoclonal antibodies (MAbs) against the IL-2 receptor alpha-chain (CD25) were evaluated as ricin A-chain immunotoxins for the treatment of Hodgkin's disease. Primary screening used an indirect assay in which the cells were treated with the test antibody followed by a Fab' immunotoxin against mouse immunoglobulin. This screening identified 5 MAbs which inhibited protein synthesis in L540 Hodgkin cells by 50% at a concentration (IC50) of 6 x 10(-11) M or less: RFT5 gamma 1, RFT5 gamma 2a, B-B10, B-F2 and B-G3. These MAbs were then linked directly to deglycosylated ricin A-chain (dgA) and were confirmed to have potent and specific toxicity for L540 cells. The immunotoxins had the following potency order: RFT5 gamma 1 greater than RFT5 gamma 2a greater than B-B10 greater than B-F2 greater than B-G3. The most effective immunotoxin, RFT5 gamma 1.dgA, had an IC50 value of 7 x 10(-12) M, which is the same as that of whole ricin. In vivo, a single intravenous injection of 48 micrograms of RFT5 gamma 1.dgA, RFT5 gamma 2a.dgA, B-B10.dgA or B-F2 induced lasting complete remissions in 78, 66, 50 and 44%, respectively, of nude mice bearing subcutaneous solid L540 tumours of 0.7 cm diameter. Two tumours which regrew after B-B10.dgA treatment were re established in tissue culture. Both had reduced sensitivity to B-B10.dgA in vitro but not to immunotoxins recognizing different antigens on Hodgkin cells. The MAbs that produced the most potent immunotoxins, RFT5 gamma 1, RFT5 gamma 2a and B B10, had no significant cross-reactivity with normal human tissues outside the lymphoid system as judged from indirect immunoperoxidase staining of frozen sections. By contrast, B-F2 strongly stained normal human renal tubules. PMID- 1917144 TI - Human tumor spontaneous metastasis in immunosuppressed newborn rats. I. Characterization of the bioassay. AB - We characterize a new model of spontaneous metastasis of human tumor cells using anti-thymocyte serum (ATS) immunosuppressed newborn rats. We analyzed the intrinsic value of the bioassay of measurement of tumorigenicity and metastatic capacity using 17 human tumor cell lines, of which were 9 human malignant melanomas. Most of these cell lines revealed as tumorigenic and metastatic in lungs and/or lymph nodes 3 weeks after s.c. injection in the ventral flank of newborn rats, irrespective of their origin. All the melanoma cell lines that we injected were tumorigenic and 77% were metastatic, whereas the same cell lines grafted in nude mice showed no evidence of metastases after 6 weeks' examination. We were not able to show any relationship between tumorigenicity in nude mice and the malignant behavior of these cells in ATS-treated newborn rats. Likewise, neither chromosome abnormalities, nor antigenic marker expression were found to be related to tumor growth in nude mice or newborn rats. Two intrinsic parameters of the model were studied: number of cells injected vs. dose of ATS injected for one melanoma cell line; and role of the 3rd and 4th injections of ATS in the establishment and development of pulmonary metastases. Moreover, we show that s.c. injection in the ATS-treated newborn rat may represent a suitable method for studying melanoma cell tumor growth and spontaneous dissemination. PMID- 1917145 TI - Inhibition by retinoic acid of hepatocarcinogenesis induced by N nitrosomorpholine and of expression of myc oncogene protein in Sprague-Dawley rats. AB - The effects of all-trans-retinoic acid (RA) on hepato-carcinogenesis induced by N nitrosomorpholine (NNM) and on the expression of myc p110 proteins were investigated in male Sprague-Dawley rats. Rats received i.m. injections of RA twice a week and, from the beginning of the experiment, were given drinking water containing NNM for 8 weeks. Pre-neoplastic and neoplastic lesions staining positively for gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase placental type (GST-P) or myc p110 protein were examined histochemically. At week 18, quantitative histological analysis showed that prolonged administration of RA resulted in a significant reduction in the number, size and volume of GGT positive and GST-P-positive hepatic lesions. Administration of RA also caused a significant increase in the proportion of myc p110-negative lesions to the total pre-neoplastic lesions observed. Myc p110-negative lesions had a significantly lower mitotic index than myc p110-positive lesions. These findings indicate that RA inhibits hepatocarcinogenesis and suggest that this effect may be related to its influence in reducing the expression of myc gene proteins and its subsequent inhibition of cell proliferation in pre-neoplastic lesions. PMID- 1917146 TI - Risk factors for cancer of the oesophagus in Kerala, India. AB - A case-control study of oesophageal cancer was carried out in Trivandrum, Kerala, involving 267 cases and 895 controls. Risk factors studied in males were pan (betel)-tobacco chewing, bidi and cigarette smoking, drinking alcohol and taking snuff. Only pan-tobacco chewing was investigated in females as very few indulged in the other habits. Among males significant associations with higher risk were observed for bidi smoking (p less than 0.001), bidi plus cigarette smoking (p greater than 0.05) and drinking alcohol (p less than 0.001). While a significant effect of duration of pan-tobacco chewing (p less than 0.005) was observed in males, there was no significant trend, the risk first falling then rising as duration of use increased. This was partly due to confounding with smoking. No effect of pan-tobacco use was observed in females. A step-wise model was fitted, retaining only those risk factors which were significant when adjusted for other factors; the risk factors included were duration of pan-tobacco chewing, duration of bidi smoking, daily frequency of bidi and cigarette smoking and alcohol use (yes or no). An adjusted relative risk of 2.03 was observed for a pan-tobacco habit of more than 40 years' duration, of 4.70 for more than 20 years of bidi smoking, of 4.80 for more than 20 bidis/cigarettes per day, and of 2.33 for regular alcohol use (in each category relative to a baseline of those never indulging in the relevant habit). PMID- 1917147 TI - Indications of future decreasing trends in skin-melanoma mortality among whites in the United States. AB - Trends in skin melanoma death rates during a 35-year period, 1950-84, were analyzed according to age, sex, and birth cohort for whites in the United States. In contrast to upward trends observed for older men and women (i.e., over 40), downward trends were noted for younger age groups. The risk of dying from skin melanoma appears to have peaked for male cohorts born during the 1950s and for female cohorts born during the 1930s. Assuming no future environmental or lifestyle changes, the upward trend in age-adjusted mortality rates, which averaged 2 to 3% per annum since 1950, is projected to discontinue and bend downward by the second decade of the 21st century. Skin melanoma incidence data, which was limited to a series of 12 years (1973-84) and inadequate for cohort analyses, were included to demonstrate that trends in age-specific rates were comparable with those observed for mortality during the overlapping time period. Incidence trends according to anatomical site are also described. These results indicate that baseline data necessary for assessing the potential effects on this disease from future depletions of the ozone layer, and predicted increases of solar ultra-violet radiation exposure, would be improved with the inclusion of cohort data and age-specific trend analyses. PMID- 1917148 TI - Characterization of gangliosides in human uveal melanoma cells. AB - We have evaluated the ganglioside composition of 20 primary uveal melanomas, of 2 cell lines derived from 2 uveal melanomas, of a liver metastasis from an uveal melanoma, and of 8 normal choroids. The results show that normal choroid tissue has a ganglioside content similar to the primary tumors of uveal melanoma except for GD1a, GD1b, and GT1b, which are present only on normal choroid tissues. On the other hand, the uveal melanomas have similarities with cutaneous melanomas, since GM3 (74%) and GD3 (25%) are found in both tissues and are present in about the same amounts. However, GM1 was found in 50%, GM2 in 20% and GD2 in none of the uveal melanomas. According to data published by others, cutaneous melanoma biopsies have no GM1, whereas GM2 is present in 100% and GD2 in 71% of tumor tissues. Transplantation of the 2 cell lines subcutaneously into nude mice resulted in the growth of tumors which had a ganglioside profile larger than that of the primary tumors. GM3 was significantly diminished and GD3 significantly increased in the primary uveal melanoma from patients who had received radiotherapy before enucleation compared with those who did not have radiotherapy. These results show that uveal melanomas contain gangliosides that could be used as targets for monoclonal antibody therapy. PMID- 1917149 TI - The systemic complement activation caused by interleukin-2/lymphokine-activated killer-cell therapy of cancer causes minimal systemic neutrophil activation. AB - Twenty-three cancer patients undergoing therapy with interleukin-2 and lymphokine activated killer cells were studied for evidence of complement activation and systemic neutrophil activation occurring during the course of therapy. Patient plasma samples demonstrated evidence of marked complement activation, with 3-fold elevations of C3a desArg concentrations by the 8th day of therapy. Concentrations of C4a desArg were also elevated by the end of therapy. In vitro chemotaxis of patients' neutrophils both to C5a and to the synthetic peptide chemotaxin, FMLP, was initially normal and then fell progressively to 60% of normal by the end of treatment. Mean neutrophil cell-surface expression of complement receptor Type 1 and complement receptor Type 3 increased in inverse temporal relationship to the deficit in chemotaxis, but showed no consistent pattern for individuals and was only doubled at maximum. Thus, despite a degree of complement activation which should have produced pronounced neutrophil activation, the response of the circulating neutrophils was diminished. In view of this discrepancy, the toxicity of this therapy may not be mediated by activation of circulating neutrophils. PMID- 1917150 TI - Univariate and multivariate analyses of the relationship between adenocarcinoma and solitary and multiple adenomas in colorectal adenoma patients. AB - In 584 consecutive patients with no previous history of cancer or polypectomy, 769 adenomas were excised endoscopically and classified retrospectively according to the following parameters: macroscopic growth pattern, size, histological type, grade of dysplasia, anatomical site, presence of adenocarcinoma (ADK), number of adenomas and sex and age of the patient. A multivariate logistic analysis confirmed that size and histological type are the 2 most important predictors of ADK, both in solitary and in multiple adenomas. Adenomas located in the sigmoid portion and in the rectum have an increased probability of ADK, independent of size and histology. Multiple polyps, when compared to solitary polyps, were more frequent in males (p less than 0.01) and were more often larger than 2 cm. Significant similarities in histology, morphology and degree of dysplasia were observed among multiple adenomas from the same patient. PMID- 1917151 TI - Dietary factors and stomach cancer in Spain: a multi-centre case-control study. AB - A multi-centre case-control study of diet and gastric cancer was carried out in 4 regions of Spain (Aragon, Castile, Catalonia and Galicia). We selected 354 cases of pathologically confirmed gastric adenocarcinoma from 15 hospitals, representative of nearly all those in the study areas. A control for each case, matched by age, sex and area of residence, was selected from the same hospital as the case. Habitual diet was investigated by the dietary history method, and past diet by means of a frequency questionnaire. The results regarding consumption of food items are presented here. With respect to habitual diet, an increase in risk was associated with consumption of preserved fish, cold cuts and oleaginous fruits. A high intake of cooked green vegetables, fresh noncitrus fruit and dried fruit showed an inverse association with the risk of gastric cancer. Simultaneous intake of 2 groups of food which increase or decrease the risk of cancer strengthens the respective individual effect. The intake of protective food items seems to neutralize the effects of food items which increase risk. With reference to past diet, a possible protective effect was observed for daily consumption of fresh fruit and green vegetables. PMID- 1917152 TI - Meat, cooking methods and colorectal cancer: a case-referent study in Stockholm. AB - The associations between methods of cooking meats and colorectal cancer were examined in a population-based case-referent study performed in Stockholm in 1986 1988. The study included 559 cases and 505 referents. Total meat intake, frequent consumption of brown gravy, and a preference for a heavily browned meat surface each independently increased the risk for colorectal cancer. The relative risks (RR) were higher for rectal than for colon cancer, and for boiled meat (RR colon = 1.7, RR rectum = 2.7) than for meat fried with a medium or lightly browned surface (RR colon = 0.8, RR rectum = 1.1), but the highest risks were for meat fried with a heavily browned surface (RR colon = 2.8, RR rectum = 6.0). The analyses were adjusted for year of birth, gender and fat intake. Further adjustments for total energy, dietary fiber intake, body mass and physical activity had little or no influence on the results. The findings suggest that, in addition to frequent meat intake, a heavily browned meat surface formed when frying meat at high temperatures is important in the etiology of colorectal cancer. PMID- 1917153 TI - Survival of breast cancer patients in relation to factors which affect the risk of developing breast cancer. AB - In order to evaluate the prognostic significance of risk factors for developing breast cancer, a population-based study was conducted of 2,445 breast cancer patients diagnosed in Denmark, 1983-1984. Data on clinical and pathological characteristics of breast cancer were derived from the Danish Breast Cancer Cooperative Group and data on risk factors from a self-administered questionnaire. Among 1,744 patients (71%) with complete information, survival was determined primarily by size of the tumour, skin invasion, number of positive lymph nodes and grade. No significant association was found between survival and reproductive or hormonal risk factors, dietary variables, alcohol consumption and smoking. Low current body weight and weight loss indicated a poor prognosis, independent of the clinical characteristics of the tumour. PMID- 1917154 TI - Breast cancer screening and cost-effectiveness; policy alternatives, quality of life considerations and the possible impact of uncertain factors. AB - Mammographic screening for women aged 50-70 is effective in reducing breast cancer mortality, but the impact on quality of life and the attainable mortality reduction remain to be discussed. The consequences of expanding screening programmes to include women in other age groups are uncertain. We have predicted the effects and costs for 5 popular screening variants, differing in age group and screening interval, on the basis of our analysis of the Dutch screening trials and of the reported mortality reductions in other trials. We have also investigated the influence of a large number of uncertain factors. Screening for women aged 50 and over with a 2- or 3-year interval is very cost-effective and will result in reductions of respectively 16% or 10% in breast cancer mortality in a real population. Variation of most variables keeps the cost-effectiveness (CE) ratio limited to the range of US $3,000 to 5,000 per life-year gained. A 2- to 3-fold change in CE ratio would only occur if the extreme estimates of mortality reduction in the Swedish screening trials were applied. The impact on quality of life (QoL) is limited: for the 2-yearly screening policy for women aged 50-70, the cost per Quality-Adjusted Life-Year (QALY) gained is 4,050, whereas the cost per life-year gained is US $3,825. The CE ratio for 2-yearly screening of women aged 40-70 is 5,400, but the additional cost per additional life-year gained is US $35,000. It would be preferable by far to extend the screening programme to women over the age of 70 or to shorten the screening interval for women aged 50-70. Screening performances, the demand for mammograms outside screening and the possibility of a survival improvement irrespective of screening have a strong impact on QoL and CE. PMID- 1917155 TI - The impact of a breast cancer screening programme on quality-adjusted life-years. AB - Trials have shown that breast cancer screening is effective in reducing breast cancer mortality and gaining life-years. The question is whether taking into account the impact of a screening programme on quality of life would lead to a less positive view. Screening may have effects on quality of life in the short run for women participating and effects in the long run as a result of the expected shift in the number of women experiencing early and advanced phases of the disease, after the initiation of the programme. In this study 4 steps have been taken: (I) published studies on quality of life and breast cancer (screening) up to 1989 have been reviewed and summarized and, based on these data, the consequences of breast cancer and treatment have been described; (2) values have been assigned to the disease and treatment phases by experts in breast cancer and public health (N = 31, response 87%); (3) these values have been inserted in the MISCAN model predicting the prevalence of disease/treatment phases with and without a 2-yearly screening programme for women aged 50-70 and multiplied by the duration of these phases; (4) analyses have been done to establish the sensitivity of the results for the values inserted. The programme of 2-yearly mammographic screening for women aged 50-70 is predicted to be 8% "less effective" (range -19.7 to +3.2%) when computing quality-adjusted life years. We conclude that this adjustment is too small to attribute a major role to quality of life in the decision to undertake a large-scale breast cancer screening programme. PMID- 1917156 TI - Abnormalities of the EGF receptor system in human thyroid neoplasia. AB - The epidermal-growth-factor receptor (EGF-r) and its ligands are involved in the control of proliferation of both normal and neoplastic thyroid epithelium. Autocrine stimulation of growth involving this receptor system has been identified in several types of human neoplasia and we were interested to determine whether it might occur in human thyroid tumours. We have therefore examined an archival series of thyroid tumours and non-neoplastic pathologies for expression of the EGF-r and 2 of its ligands, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF), using immunohistochemistry. We found evidence of expression of both the EGF-r and the TGF-alpha in the majority of thyroid tumours, with a trend to higher expression in more malignant neoplasms. We also found variable levels of expression of EGF-r and TGF-alpha in all cases of thyroiditis examined. We conclude that there is a potential autocrine loop involving the EGF-r system in both neoplastic and non-neoplastic conditions of the human thyroid. PMID- 1917157 TI - Concentrations of oestrone and 4-hydroxyandrostenedione in malignant and normal breast tissues. AB - 4-Hydroxyandrostenedione (4-OHA) is a specific inhibitor of aromatase activity used for the treatment of breast cancer in post-menopausal women. Treatment with 4-OHA has been shown to inhibit the peripheral conversion of androstenedione to oestrone and reduce plasma oestrogen concentrations, but the effect of treatment on breast-tissue oestrone concentrations is not known. We have therefore examined the effect of treatment with 4-OHA on oestrone concentrations in normal and malignant breast tissues and also measured plasma and tissue 4-OHA concentrations. Changes in tumour oestrone concentrations were related to DNA polymerase alpha activity, a marker of cellular proliferation. Blood and breast tissue samples were obtained before and 36 hr after treatment with 4-OHA. The mean plasma concentration of 4-OHA was 27.9 +/- 19.3 ng/ml, compared with levels of 33.7 +/- 25.6 ng/g for breast tumour and 13.5 +/- 11.5 ng/g for normal breast tissue. There was a significant correlation between 4-OHA concentrations in plasma and normal breast tissue (r = 0.91, p less than 0.001). Treatment with 4 OHA resulted in a significant (p less than 0.02) decrease in breast-tissue oestrone concentrations. For 3/4 tumour samples, a marked decrease in the concentration of oestrone (78 +/- 4%) was associated with a similar decrease (64 +/- 16%) in DNA polymerase alpha activity. It is concluded that treatment with 4 OHA effectively reduces breast-tissue exposure to oestrogen. PMID- 1917158 TI - Efficacy and selectivity of monoclonal-antibody-targeted drugs and free methotrexate in fluorescence-labelled mixed tumour-cell monolayer cultures and multicellular spheroids. AB - Free methotrexate (MTX) and 2 monoclonal antibody (MAb)-MTX conjugates were tested against mixed human tumour-cell cultures, in which 2 cell lines of differing antigenicity or drug sensitivity, pre-labelled with fluorescent dyes, were added together in microtitre wells. Conjugates were selectively cytotoxic for cells bearing high concentrations of the relevant antigen, and MTX was preferentially cytotoxic for wild-type cells rather than MTX-resistant variants when tested on separate cultures. In mixed cultures these selectivities were substantially retained, although there was a varying tendency towards intermediate cytotoxicity for each cell line of the pair. MTX was cytotoxic for cell line 79 IT grown as multicellular spheroids, but a MAb-MTX conjugate and a MAb-RTA immunotoxin showed little cytotoxicity against spheroids at the highest concentrations tested, although they were highly effective against monolayer cells. Mixed spheroids could be formed efficiently from most cell lines, although in some cases cell distribution was non-random. In mixed spheroids prepared between wild-type and MTX-resistant 79 IT variants, relative MTX sensitivities conformed broadly to those seen in separate monolayer cultures. Fluorescence labelling was a reliable method for determining cell behaviour under the above conditions. We conclude that (a) selectivity of therapeutic agents in mixed cultures was partially, but not completely, impaired compared to that observed in separate cultures, and (b) that low Mr drugs are effective against 3-dimensional tumour-cell structures but antibody-targeted conjugates are not. PMID- 1917160 TI - Putrescine and spermidine uptake is regulated by proliferation and dexamethasone treatment in AR4-2J cells. AB - Polyamines are essential for cell growth and differentiation. Their specific uptake contributes to the regulation of intracellular polyamine levels. In this study, we describe the modulation of this transport mechanism in a rat tumoral pancreatic acinar cell line (AR4-2J) and analyze the transport system characteristics of the normal rat pancreatic acini. Normal acini had a common carrier for spermidine and spermine, like AR4-2J cells, but not a specific putrescine carrier. Intracellular polyamine deprivation enhanced putrescine and spermidine uptake of AR4-2J cells with no modification of polyamine carrier affinity. Uptake was modulated during growth and decreased for both polymaines at confluence. AR4-2J cell differentiation with dexamethasone prevented cell proliferation and diminished uptake of both putrescine and spermidine without affecting their respective carrier affinities. Our data show, first, that the polyamine transport system could be modulated by polyamine metabolism with no change in its affinity characteristics. Second, in rat pancreatic acinar cells, neoplastic transformation was partly characterized by induction of a high affinity putrescine carrier. This phenotype was not reversed by dexamethasone induced cell differentiation. PMID- 1917159 TI - Enhancement of anti-neoplastic activity of cytosine arabinoside against human HL 60 myeloid leukemic cells by 3-deazauridine. AB - Drug resistance is one of the major reasons for failure of chemotherapy of acute leukemia with cytosine arabinoside (ARA-C). In order to overcome this problem we have investigated the interaction of ARA-C with 3-deazauridine (3-DU) against HL 60 myeloid leukemic cells. 3-DU is an interesting agent to use in combination with ARA-C, since drug-resistant cells that are deficient in deoxycytidine kinase are very sensitive to this uridine analogue. We have observed that for both short and long drug exposure there was a potent synergistic interaction between ARA-C and 3-DU with respect to their cytotoxic effects on HL-60 leukemic cells. This synergy could be explained by an increased cellular uptake of ARA-C to ARA-CTP by the leukemic cells in the presence of 3-DU, due to the reduction in the pool of dCTP produced by this latter analogue. Since dCTP is a potent feedback inhibitor of the phosphorylation of ARA-C by deoxycytidine kinase, the reduction in the dCTP produced by 3-DU results in an increased rate of phosphorylation of the arabinosyl analogue. Our results suggest that ARA-C and 3-DU may be an interesting drug combination to circumvent drug resistance in the chemotherapy of acute leukemia. PMID- 1917161 TI - Dipyridamole enhancement of doxorubicin-induced translocation of nucleophosmin and inhibition of cell growth in HL-60 cells. AB - Dipyridamole (DPM) enhanced sensitivity to doxorubicin (DOX) in a human leukemia cell line that was already relatively sensitive to this agent. Using an immunofluorescence technique, we determined the localization of nucleophosmin (protein B23) in HL-60 cells after incubation with DOX in the absence and presence of DPM. Bright nucleolar fluorescence was observed in control HL-60 cells. The addition of DOX (0.1-0.25 micrograms/ml) in the culture system resulted in time- and dose-dependent induction of nucleophosmin translocation from the nucleolus to nucleoplasm and inhibition of cell growth. DPM (5 microM) alone had no effect on nucleophosmin translocation and inhibition of cell growth. However, the addition of DPM to the cells enhanced DOX-stimulated translocation of nucleophosmin. There was a good correlation between the DPM enhancement of DOX induced nucleophosmin translocation and the increased inhibition of cell growth. The cell number decreased to a greater extent within a shorter time period under treatment with DOX in the presence of DPM. Short exposure (0.5 hr) of HL-60 cells to DOX induced dose-response nucleophosmin translocation and cell growth inhibition. Such effects of a short exposure to DOX were also enhanced by DPM (5 microM) included in the fresh medium after removal of DOX. This was in agreement with the observation that DPM could increase the cellular DOX by inhibiting the drug efflux from the cells. These results demonstrate that DPM, being able to increase and retain the intracellular levels of DOX, can markedly enhance the cytotoxicity of DOX, and suggest possible clinical application. "Nucleophosmin translocation", as observed by immunofluorescence, could be useful in determining the efficacy of combinations of DOX and DPM in cancer chemotherapy. PMID- 1917162 TI - Peri-tumor interleukin-2 causes systemic therapeutic effect via interferon-gamma induction. AB - This study compares the direct local therapeutic effects of multiple peri-tumor injections of interleukin-2 (IL-2) and interferon gamma (IFN-gamma), also the associated systemic therapeutic effects on distant untreated tumors resulting from the peritumor injections. The therapeutic effects were tested against intramammary implants of an immunogenic, syngeneic C3H mammary carcinoma. Peritumor IL-2 and IFN-gamma had nearly equal local and systemic therapeutic effects. In a comparison of the therapeutic effects of IL-2 and IFN-gamma injected systemically, only the IFN-gamma injections resulted in a significant number of cures. IL-2 and IFN-gamma did not have an additive effect when used in combination, suggesting that they have connected, rather than separate, paths of action in the anti-tumor immune response. The injection of anti-IFN-gamma-MAb abrogated the systemic therapeutic effect of peri-tumor IL-2, indicating that the systemic therapeutic effect was the result of IFN-gamma induction at the IL-2 injection site. PMID- 1917163 TI - Kinetics of biochemical, electrophysiological and morphological events (including lysosomal disorder) during the course of suramin-induced differentiation of the human colon-cancer cell clone HT29-D4. AB - Suramin, a polysulfonated naphtylurea, has been shown to bind to a wide variety of tumor growth factors, and to exhibit anti-proliferative effects on several cell lines. We have followed the suramin-induced (100 micrograms/ml) evolution of morphological, biochemical and electrophysiological changes in HT29-D4 human colonic adenocarcinoma cell clone as a function of culture time. After 5 days of culture in the presence of the drug the cells were polarized and exhibited apical brush border and tight junctions. The polarization process of carcino-embryonic antigen (CEA) in the apical membrane domain was achieved after 8 days of treatment, while the correct localization of HLA class-I molecules in the basolateral membrane domain occurred after 14 days of culture in the presence of suramin. Spontaneous potential difference (PD) and transepithelial resistance (Rt) were recorded from the 9th day of treatment and reached maximum values at day 15 (PD = 3 mV; RT = 450 omega cm2), giving evidence that the differentiation process triggered by suramin concerned virtually all cells in the monolayer. Untreated cells were consistently found to be electrically inactive. Finally, from day 10 of suramin treatment, the lysosomal system was perturbed including accumulation of large autophagic vacuoles and, later, typical lamellar inclusion bodies. These structures were never seen when cells were induced to differentiate in suramin-containing serum-free medium. Moreover, similar perturbations of the lysosomal system could be obtained by adding BSA in the suramin-containing defined medium, suggesting that the lysosomal storage disorder occurring upon suramin treatment was due to endocytosis of suramin-BSA complexes. We conclude that lysosomal impairment due to the presence of BSA in the culture medium did not prevent HT29-D4 cells from differentiating and that it was not an early event which could be involved in the mechanism of action of suramin. However, this perturbation might account for some of the toxic effects occurring during chronic suramin treatment in humans. PMID- 1917164 TI - Improvement by affinity chromatography on antiidiotypic monoclonal antibodies (MAbs) of immunoreactivity and in vivo targeting of radiolabelled anti-HMW-MAA MAb TP61.5 in nude mice bearing human melanoma lesions. AB - The human high-molecular-weight melanoma-associated antigen (HMW-MAA) represents a useful marker for immunoscintigraphy in patients with melanoma. Since injection of a radiolabelled anti-HMW-MAA monoclonal antibody (MAb) visualizes only about 60% of melanoma lesions, approaches are being developed to increase the sensitivity of immunoscintigraphy. One of them aims at improving the immunoreactivity of radiolabelled anti-HMW-MAA MAbs, since this approach may improve the targeting of radiolabelled MAbs to melanoma lesions. We have previously shown that affinity chromatography on insolubilized anti-idiotypic MAbs is a useful method for purifying immunoreactive anti-HMW-MAA MAb TP61.5 from 125I-labelled MAb preparations and that not all the anti-idiotypic MAbs are useful for this purpose. Since the increasing number of available anti-idiotypic MAbs is likely to facilitate the application of this procedure in many antigenic systems, we have now tested criteria to select anti-idiotypic MAbs suitable for the purification procedure. Furthermore, we have investigated the effect of the increase in immunoreactivity of 125I-MAb TP61.5 on its in vivo targeting to human melanoma lesions transplanted into nude mice. Among the 3 anti-idiotypic MAbs tested, the most effective in purifying immunoreactive MAb TP61.5 molecules following radiolabelling is MAb TK7-110, with which 125I-MAb TP61.5 displays an immunoreactivity similar to that displayed with melanoma cells. This parameter may represent a useful criterion to identify anti-idiotypic MAbs suitable for the purification procedure, if the present results are confirmed with a large number of anti-idiotypic MAbs in different antigenic systems. We have also shown that an incubation time for up to 4 hr of 125I-MAb TP61.5 with insolubilized MAb TK7-110 is the most effective in increasing immunoreactivity and in recovering immunoreactive MAb applied to the affinity matrix. The increase in the immunoreactive fraction of 125I-MAb TP61.5 significantly increases its specific localization in human melanoma lesions transplanted into nude mice. These results suggest that purification of radiolabelled immunoreactive anti-HMW-MAA MAb TP61.5 by affinity chromatography using anti-idiotypic MAb TK7-110 represents a useful approach to increasing the sensitivity of immunoscintigraphy in patients with melanoma. PMID- 1917166 TI - Simplifying the understanding of congenital malformations of the heart. PMID- 1917165 TI - Induction of multiple-drug resistance during anti-neoplastic chemotherapy in vitro. AB - Induction of P-glycoprotein-related multi-drug-resistance (MDR) has been shown in normal and malignant tissues to result from environmental stresses such as heat shock, exposure to carcinogens or X-ray irradiation. To identify conditions under which MDR is enhanced during anti-neoplastic chemotherapy, a cell line showing low-level intrinsic MDR was investigated. In the pleural mesothelioma cell line, PXF1118, less than 1% of cells expressed P-glycoprotein (P-gp), as shown by immunocytochemical staining with monoclonal antibody (MAb) MRK16. Exposure of PXF1118 to vincristine, vindesine, vinblastine or doxorubicin for 2-3 weeks led to an increase in the MDR cell fraction of up to 15-28% during 2 to 3 weeks. For doxorubicin and vindesine, dose-dependence was observed: drug concentrations not capable of eliciting cytotoxicity failed to induce significant P-gp expression. Nutrient starvation in aging medium, exposure to activated cyclophosphamide (even at high concentrations) or cisplatin caused only negligible MDR induction. After exposure to vindesine for 6 weeks, tumor colonies exhibited highly enhanced resistance to Vinca alkaloids, doxorubicin, etoposide and dacarbacine, whereas their sensitivity to mitomycin, activated cyclophosphamide or cisplatin remained unchanged. As determined by [3H]-thymidine uptake and proliferation antigen expression, induction of MDR phenotype was observed at minimal proliferative activity with no change in cell count during exposure to anti-cancer drugs, thus suggesting that the drug treatments changed the phenotype of the cells rather than selecting for a resistant sub-population. In addition, changes in cell differentiation were observed during MDR induction. Induction of P-gp during exposure to anti-cancer drugs thus provides a model for MDR development during initially successful chemotherapy. of P-gp during exposure to anti-cancer drugs thus provides PMID- 1917167 TI - Paediatric cardiology in the first decade of the International Journal. PMID- 1917168 TI - Advances in the understanding of systolic and diastolic functions of the heart. PMID- 1917169 TI - Advances in pacing therapy for bradycardia. AB - Advances have been made rapidly in the field of cardiac pacing. The most significant technologic advance is that of pacemakers capable of rate-adaptive pacing. Multiple types of sensors are now used for rate-adaptive pacing; some are commercially available and many are undergoing clinical investigation. In the near future, clinical investigation will begin on pacemakers that incorporate dual simultaneous sensors for rate-adaptive pacing. Significant improvement has been made in electrode design. Electrodes with low thresholds allow improved battery longevity. Steroid-eluting leads have proven reliable and capable of avoiding the early threshold rise seen with other electrodes. Standardization of pacemaker connector dimensions is now under way. The International Standards Organization has established the guidelines for connector standardization, and the guidelines have been adopted by the major manufacturers. The ultimate "smart" pacemaker would be capable of autoprogramming most or all of its programmable features. Many autoprogramming features have already been incorporated, and several others such as automatic programming of output and sensitivity are under investigation. PMID- 1917170 TI - Hotline at the European Society of Cardiology: what questions will these multicentric trials answer? PMID- 1917171 TI - Cardiovascular pathology, quo vadis? PMID- 1917172 TI - Morphogenetic considerations on congenital malformations of the outflow tract. Part 1: Common arterial trunk and tetralogy of Fallot. AB - On the basis of our recent embryologic work concerning the separation process of the outflow tract, together with our study of the morphology of specimens from the Leiden Collection of malformed hearts, we have reconsidered, in conjunction with the pertinent literature, the morphogenesis of common arterial trunk and tetralogy of Fallot. The constant characteristics of common arterial trunk, namely a common trunk, a common arterial orifice and a ventricular septal defect, can be explained simply by absence of the aorto-pulmonary septum, or its complete failure to contribute to the process of separation. The nature of the variable morphologic features, however, is not always clear. Presence of such variation is not contradictory to the explanation of the main characteristics in this malformation. Tetralogy of Fallot, in contrast, can be considered to result from anterior displacement of the columns of the aorto-pulmonary septum relative to the outlet segment and its proximal boundary, the primary fold. Our findings, and suggestions, diverge considerably from conventional theories concerning the morphogenesis of these malformations. PMID- 1917173 TI - The role of medical treatment of distal type aortic dissection. AB - We analyzed the short-term and long-term outcome of 42 patients with distal type aortic dissection. Twenty-eight patients underwent intensive medical therapy within two weeks after the onset of pain (acute dissection). The remaining 14 patients had chronic dissection. The goals of medical treatment were to control blood pressure and to attain a negative C-reactive protein test result. Hospital survival rate in the patients with acute dissection was 96% (27/28). In-hospital complications included changes in mental status, renal dysfunction, bradycardia, orthostatic hypotension, and liver dysfunction, all of which were managed medically. Three of these patients underwent surgical therapy in the chronic phase and were discharged uneventfully. Fifteen (62.5%) of the 24 medically treated patients were discharged with negative C-reactive protein tests. Spontaneous resolution of a dissection was demonstrated by radiological examinations in 8 cases. Five-year survival rates in 24 medically treated patients was 93%. Hospital survival rate in the patients with chronic dissection was 100% (14/14). The rigorous control of blood pressure in the acute phase, and subsequent meticulous evaluation of the dissection by radiological tests and C reactive protein test provides acceptable short-term and long-term outcomes of patients with acute distal dissection without the need for emergency surgical intervention. PMID- 1917174 TI - Efficacy of continuous and intermittent transdermal treatment with nitroglycerin in effort angina pectoris: a multicentric study. The Collaborative Nitro Group. AB - Eighty-eight patients (84 men and 4 women; mean age 59.3 years) with stable exercise-induced angina pectoris were enrolled in this within-patient, placebo controlled study aimed at comparing the efficacy of the continuous and intermittent (12 hour on, 12 hour off) application of transdermal nitroglycerin. Eighty-one patients completed the study. After a 1-week placebo run-in period, during which the stability of angina was assessed on a bicycle ergometer, the patients received continuous treatment (two 10 mg/24 hour patches twice daily, at 8 a.m. and 8 p.m.), intermittent treatment (two 10 mg/24 hour patches at 8 a.m. and two placebo patches at 8 p.m.) and placebo (two placebo patches twice daily, at 8 a.m. and 8 p.m.), each given for one week in a double-blind randomised sequence, according to a 3 x 3 latin-square design. A cycloergometric exercise test was performed at the end of each period of treatment, 4 and 10 hours after the application of the morning patch. In comparison with placebo, both schedules of the active treatment induced a significant increase in both the ischemic (duration of exercise to 1 mm ST segment depression) and the angina threshold (duration of exercise to mild angina) at the 4th and at the 10th hours after dosing. A significant difference was also found between continuous and intermittent treatment at the same times of observation, in favour of the intermittent schedule. The limited number of anginal attacks recorded during placebo prevented any clinical evaluation of the treatments. This study shows that the efficacy of transdermal nitroglycerin is more pronounced when it is given following an intermittent schedule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917175 TI - Respiratory syncytial virus and supraventricular tachycardia in an infant. AB - A 7-week infant admitted with bronchiolitis proven to be caused by respiratory syncytial virus developed a supraventricular tachycardia which responded to digitalization. She has remained well and no longer requires medication 6 months later, her electrocardiogram now being normal. The course of the illness suggests an association between infection with respiratory syncytial virus and the development of the tachycardia. PMID- 1917176 TI - Doppler echocardiography of double orifice of the left atrioventricular valve in atrioventricular septal defect. AB - A left atrioventricular valve having a double orifice is a rare congenital abnormality, and is most commonly described in association with atrioventricular septal defect. We report the Doppler echocardiographic findings of this abnormality and present a case where limited surgical repair has resulted in a favourable outcome. PMID- 1917178 TI - Angiographic appearance and re-operation in an adult patient with the Bland Garland-White syndrome. AB - Reconstructive surgery was performed in a 57-year old woman in whom initially the left coronary artery had originated from the pulmonary trunk, producing progressive symptoms of congestive heart failure. Recurrence of shunting was documented by Doppler echocardiography and contrast angiography, necessitating a second surgical intervention 17 months after the first procedure. PMID- 1917177 TI - Pulmonary venous atrial systolic flow reversal detected by transthoracic Doppler as a sign of congestive heart failure: a case report. AB - Reversal of flow in the pulmonary veins during atrial contraction was detected by transthoracic pulsed Doppler echocardiography in a patient with bicuspid aortic valve and heart failure. The flow reversal disappeared after his recovery from heart failure. Flow reversal during atrial contraction detected by transthoracic Doppler may be a sign of congestive heart failure. PMID- 1917179 TI - Free-floating ball thrombus in left atrium: pathological features and clinical implications. AB - A patient with a free-floating ball thrombus in the left atrium complicating mitral stenosis is described. The pathological features and clinical implications are discussed. PMID- 1917180 TI - Pustular osteoarthropathy and its differential diagnosis. AB - A combination of costo-sterno-clavicular hyperostosis and palmo-plantar pustulosis, sometimes with hyperostotic spondylosis and spondylarthritis, is called pustular osteoarthropathy. In the Western hemisphere 40 cases have been reported and in the Far East the condition occurs more commonly. Five cases are described. Diagnosis is difficult because the skin lesions can occur before the costo-sterno-clavicular hyperostoses. The clinical condition is discussed together with the differential diagnosis. Pustular osteoarthropathy seems to be an enthesopathy and the palmoplantar pustulosis is interpreted as a form of psoriasis. PMID- 1917181 TI - Metastatic fractures of long bones. AB - Forty-two patients with a total of 52 metastatic fractures of long bones were analysed retrospectively with regard to the type of treatment, complications, general mobility and survival. Endoprosthetic replacement appeared to be better than osteosynthesis in the proximal femur, and this method should also be considered in pathological fractures of the distal femur. Nailing is indicated in fractures of the shafts of long bones in the lower limb, and also in the humerus. Osteosynthesis with a plate has only limited indications. Cement should be added to an osteosynthesis or replacement of a pathological fracture in order to achieve immediate stability. On the whole, the life expectancy of these patients has improved; five in our series lived for more than 6 years after the treatment of their metastases. The method of surgical treatment therefore needs more consideration. PMID- 1917182 TI - The development of osteosarcoma in four-fold selected group of patients. AB - Patients with osteosarcoma have been submitted to four-fold selection using parameters previously shown to be associated factors. These are sex, age at onset, haptoglobins and histological type. Further data have been added to the final resulting sequence of patients. In the four-fold selected group there is an age-dependent AB0 distribution which confirms the relevance of the criteria used and, consequently, the influence on sarcoma development. It can be assumed from these investigations that the occurrence of osteosarcoma is modified by several genetically fixed factors (HP type, sex, AB0 group). PMID- 1917183 TI - Tumours of the patella. AB - We report 15 cases of primary tumours and pseudotumours of the patella. The radiographic features and the surgical treatment of the different histological types are described in relation to Enneking's surgical staging and data derived from the literature. PMID- 1917184 TI - Osteosarcoma following a fractured shaft of femur. A case report. AB - A boy, aged 14 years, sustained a fracture of the midshaft of the femur. This was treated conservatively and healed in 13 weeks. One year later an osteosarcoma developed at the site of the healed fracture. PMID- 1917185 TI - Delayed changes of vascular permeability in the cat's spinal cord following continuous electrical stimulation. AB - Liquefactive necrosis coexistent with alteration of vascular permeability was studied following electrical stimulation of the spinal cord. Evans blue albumen complex (EBA) (2.5%) was perfused one hour before electrical stimulation for 30 min with 10 mA current of 0.3 msec duration at a frequency of 20 Hz. Perfusion with saline and formalin was carried out at 0, 1, 3, 6 and 12 h after stimulation had been completed. Results were independent of the time lapse after completion of the stimulation. Liquefactive necrosis, swelling and moniliform degeneration and myelinoclasia of the myelin sheath were noted only in the external layer of the white matter. EBA leakage occurred, but there was no further expansion with time. PMID- 1917186 TI - [Results of the surgical treatment of chronic hematogenous osteomyelitis of the tibia. A series of 122 cases]. AB - Between 1968 and 1987 the authors treated 122 cases of chronic haematogenous osteomyelitis of the tibia by operation. The procedures used were drilling, sequestrectomy, and saucerisation, with bone resection in 2 cases. Operation was combined with chemotherapy for between 10 and 60 days. Eleven patients, thought to be healed, were lost to follow-up after 4 months. The remainder were reviewed for between 4 and 288 months, 97 for more than one year. After the first operation 102 patients healed completely, while 20 relapsed. Of these, 12 were treated by further operation and 8 by drainage of the abscess. Two patients relapsed twice and another 4 times. When last seen 110 patients were healed, 6 had an intermittent discharge and 6 had a permanent sinus. Special features of chronic osteomyelitis of the tibia are discussed, including destructive lesions of the knee and tibio-tarsal joints, a high incidence of axial deformity, indications for particular surgical approaches, the use of cancellous grafts and arguments against bone resection. The lesions carry a relatively good prognosis. PMID- 1917188 TI - Displaced femoral neck fractures treated with the Gouffon pin. AB - One hundred fractures of the neck of the femur, Garden stage III or IV, were treated with Gouffon pins during a three year period. Seventy-nine were followed from 24 to 52 months. Union occurred in 59 fractures. Eighteen fractures did not unite and 2 became redisplaced within the first week. Avascular necrosis was noted on radiographs in 14 of the 59 united fractures. A higher pin migration rate was found in Garden stage IV fractures, and in the failures. PMID- 1917187 TI - Infective iliopsoas bursitis. A case report. AB - We report a case of infective iliopsoas bursitis, and to our knowledge a similar case has not been described. The anatomical relation between the bursa and the hip, and related pathological conditions are reviewed. The contribution of CT guided catheterisation is emphasised as it allows aspiration of fluid, injection of radio-opaque material and lavage. PMID- 1917189 TI - Fracture with loss of the proximal femur in a child. A case report. AB - An 8 year old child was involved in a road accident and sustained a large wound in the left groin; radiographs showed a fracture with loss of the proximal femur. After skeletal traction for 80 days, there was bony regeneration of the proximal femur. At 8 months she was able to walk without support and her left leg was 2 cm only shorter than the right. PMID- 1917190 TI - Discoid lateral meniscus. AB - Discoid meniscus is uncommon and usually affects the lateral meniscus. We present 16 patients (8 male and 6 female) with tears of a discoid lateral meniscus occurring in 1800 arthroscopies. We carried out an arthroscopic partial meniscectomy leaving an intact peripheral rim. This is biomechanically satisfactory and the early results are encouraging. PMID- 1917191 TI - Longterm analysis of Sheehan total knee arthroplasty. AB - Sheehan total knee arthroplasty was carried out in 405 knees at two centres. The patients were followed up from two to eleven years. The clinical results were assessed, the complications documented and the influence of specific factors on the result was evaluated. The principal complications arose from the patella and the femorotibial articulation. The low rate of loosening and the achievement of satisfactory alignment lead the authors to support the concept of a long stem. PMID- 1917192 TI - Sonography in the diagnosis of painful hips. AB - We report our use of linear sonography in evaluating painful and irritable hips. Images were correlated with the clinical course and outcome, and other methods of diagnostic imaging. Sonography demonstrated the anatomical structures of the hip, the joint space and capsule. A significant increase of joint space due to the progressive development of intra-articular fluid was found in patients with transient synovitis, septic arthritis and osteomyelitis of the femoral neck. Sonography and CT scanning appear to be the most reliable methods of making an early diagnosis of various hip disorders. Both allow serial examination for evaluating the patients' clinical progress. Sonography has the advantages of being noninvasive, cheap, easy to use, and devoid of irradiation or any other known complications. PMID- 1917193 TI - Experimental study on allogenic bone grafts. AB - The effects of various processing techniques on the biomechanical properties and the histological incorporation of bone grafts were investigated in a rat model over a 6 month period. The stiffness of bone increased after freezing to -80 degrees C and freeze-drying. Decalcified bone was very soft. Visco-elasticity was pronounced at 4 to 12 weeks and the stiffness of the graft increased at 16 weeks. This progressive rise in stiffness was in line with the progressive incorporation of the graft. The bone incorporation ratio is proposed as a histological indicator of osteo-inductive properties. It was found to be best in fresh autografts, followed by processed allografts (frozen, freeze-dried and decalcified) and fresh allografts. The values of these 3 groups showed a statistically significant difference. PMID- 1917194 TI - Isolated contracture of the long head of biceps femoris muscle. AB - A rare case of contracture of the long head of biceps femoris in a soccer player is described. Degeneration was probably caused by repeated corticosteroid injections. He made a full recovery after release of the shortened long head. PMID- 1917196 TI - Solitary metastasis of the patella as the first manifestation of lung cancer. PMID- 1917197 TI - The relation of low grade mental ability to fractures in young men. AB - Reaction time, choice reaction time and mental ability were measured in a sample of 123 young men. Previous musculoskeletal injuries were noted. Eight subjects who had experienced a bone fracture in the preceding 20 months had significantly longer choice reaction time and poorer mental ability test results than the non injured. This preliminary result shows that long choice reaction time and poor performance on mental ability tests are associated with accidental musculoskeletal injuries. PMID- 1917195 TI - Bone morphogenetic protein: a review. AB - The osteogenic potential of bone and bone matrix has been characterised only by its biological effects and the parameters influencing it. Recently, the osteoinductive ability of bone matrix had been defined chemically by the description of a bone morphogenetic protein (BMP), and the parameters of osteogenic factors from different species have now been recognised. The current state of isolation, purification and characterisation of these factors is summarised in this review. General aspects of the isolation and testing of BMP preparations, and the results of orthotopic application of BMP implants, including clinical cases, are reported. PMID- 1917199 TI - [Idiopathic aseptic osteonecrosis of the capitate bone. Literature review apropos of 3 new cases]. AB - The authors report 3 cases of idiopathic avascular necrosis of the capitate and review them together with published reports of 16 further cases. The patients are normally young and the diagnosis delayed. The radiographs may demonstrate an eggshell appearance, a sequestrum, marked sclerosis, or cystic changes. A classification is proposed based on the portion of the bone involved. Early osteoarthritic changes occur and carpal instability may develop. It is suggested that there are features in the blood supply which may be significant. Treatment is by operation, involving either excision of the capitate with replacement with a prosthetic spacer, or else by arthrodesis. PMID- 1917198 TI - Arthroscopic distension in the management of frozen shoulder. AB - We report a prospective study comparing the results of treatment for frozen shoulder by manipulation and physiotherapy, arthroscopic distension and physiotherapy, and physiotherapy alone in 75 patients. The first two gave better results than physiotherapy alone and we recommend arthroscopic distension as a good alternative to manipulation. It is more controllable and gives valuable information about the pathological lesions in the joint. PMID- 1917200 TI - Thrombocytopenia and absent radius (TAR) syndrome. AB - We give details of seven children with the TAR syndrome, Thrombocytopenia with absence of the radius. Two of the children were siblings. The TAR syndrome is characterised by hypomegakaryocytic thrombocytopenia and bilateral absence of the radius. It is inherited as an autosomal recessive trait. PMID- 1917201 TI - The relevance of the U.S. experience to the reforms in the British National Health Service: the case of General Practitioner Fund Holding. AB - This article presents a discussion of the relevance of the U.S. experience in general, and health maintenance organizations in particular, to the reforms advocated by the current Conservative government in the general practitioner services of the British National Health Service. The author analyzes empirical information relevant to the assumptions made by the Conservative reformers that (1) the HMO type of practice is better able to respond to people's needs than are current general practitioner arrangements; (2) entrepreneurship in medicine is good for patients; (3) market-based primary care is more efficient than the nonmarket system in the United Kingdom; and (4) the expansion and strengthening of the private sector is an efficient and equitable means of encouraging competition and raising revenues. All of these assumptions are questioned. PMID- 1917202 TI - Paying the hospital: American problems and foreign solutions. AB - Hospital financing in the United States suffers from many problems. Many persons lack access because they lack third-party coverage. Among those covered, benefits vary, and persons receive unequal services. Costs are high and are uncontrolled. The hospital is burdened by complicated relations with many payers. In order to cover their costs and earn extra cash, hospitals overcharge the more generous third parties, and recriminations result. All other developed countries have either statutory health insurance, national health services, or full public financing of privately managed hospitals. Whatever the financing method, all countries avoid the problems prevailing in the United States. All citizens are covered, all have access, and hospitals reject no one for financial reasons. All citizens have equal benefits and receive the same basic services. Regulation by government and negotiations with health insurance carriers guarantee the hospital's operating costs to service its catchment area adequately, but also prevent the hospital from installing excessive equipment and excessive staff. Each hospital is paid by all-payer standard rates, administration of reimbursement is simple, and shifting of costs among payers is both unnecessary and administratively impossible. Costs are contained by the total management of the system, not by fragmented efforts by separate insurance carriers. Considerable strategic thinking by government, the providers, and other interest groups sets guidelines for spending levels every year to meet the country's clinical needs but also to stay within its fiscal capacity. Capital investment for new treatments depends on government grants and evaluation of needs. PMID- 1917204 TI - Addressing the contradictions: health promotion and community health action in the United Kingdom. AB - Within mainstream health education/promotion in the United Kingdom, the last few years have witnessed an upsurge of interest in community development, sometimes coupled with an undermining of the fundamental principles of this approach. This article addresses some of the contradictions and dilemmas that this development has presented for the community health movement. Current trends in health promotion policy and practice are examined in relation to broader health and welfare policy of the 1980s, the history of community development in health, and the background to the World Health Organization's "Health for All by the Year 2000" and health promotion initiatives. The possibilities and limitations of utilizing the rhetoric, to support community health action, are explored with reference to recent attempts by the community health movement to "reclaim" Health for All. PMID- 1917203 TI - Medical selection: Auschwitz antecedents and effluent. AB - Medical selection in Auschwitz represents the penultimate application of the traditional paradigm of medicine: the physician as gatekeeper and decision maker. The historical evolution of that role is considered in the context of public health, medical police, quarantine, and immigration. In Nazi Germany the physician was assigned responsibility for selection on behalf of the state. The ethical implications of medical selection are considered in the context of medicine today in an age of sophisticated biotechnology, constrained resources, and an aging population; an age in which the medical profession has yet to establish a fundamental system of values. PMID- 1917205 TI - Community action for health promotion: a strategy to empower individuals and communities. AB - Health status is directly affected by environmental conditions and by personal health-related behaviors, and it is indirectly affected by environmental conditions that themselves influence health behaviors. A comprehensive approach to health promotion, therefore, should encourage individuals to adopt and maintain personal behaviors that would prevent disease and promote health; discourage health-damaging personal behaviors by individuals and facilitate people engaging in health-promoting behaviors; and eliminate health hazards from the physical and social environment and make that environment more health promoting. This comprehensive approach would require social and community action to change environmental conditions as well as efforts to change individual behavior. A model of health promotion interventions is developed within which community action plays a central role. The author then presents a model of community organization to influence public policy to achieve health promotion goals. The community organization model, previously tested in comparative case study research, is illustrated with examples drawn from appropriate health promotion programs. PMID- 1917206 TI - Crisis, neoliberal health policy, and political processes in Mexico. AB - The Mexican case represents an orthodox neoliberal health policy in the context of the structural adjustment adopted by the Mexican government in 1983. The social costs of this strategy are very high, including an increase in unemployment, wage depression, regressive redistribution of wealth, and profound changes in social policies. These transformations are reflected in the health sector, where the four main axes of neoliberal policy--expenditure restrictions, targeting, decentralization, and privatization--have been implemented. This represents a change in social policy from a model based on citizens' social rights and the state's obligation to guarantee them, to a model characterized by selective public charity. This strategy has been imposed on society as a result of the Mexican corporative political regime based on a state party system. Since 1985, however, there has been a growing process of independent organization of civil society. This led in the presidential elections of 1988 to the defeat of the candidate of the governing party by the candidate of a popular-democratic opposition front. Although the government party imposed its candidate through electoral fraud, social mobilization against neoliberal policies continues in the midst of an important political crisis that can only be resolved by profound democratization of Mexican society. PMID- 1917207 TI - Poverty crisis in the Third World: the contradictions of World Bank policy. AB - Politicians, the mainstream media, and orthodox social science have all been telling us of a final victory of capitalism over socialism, suggesting that capitalism is the only viable option for solving the world's problems. Yet, the global capitalist system is itself entering the third decade of a profound structural crisis, the costs of which have been borne largely by the exploited and oppressed peoples of the underdeveloped periphery. While the World Bank's latest World Development Report recognizes the current poverty crisis in the third world, its "two-part strategy" for alleviating poverty is based on an inadequate analysis of how peripheral capitalist development marginalizes the basic needs of the third world poor. Hence, the World Bank's assertion that free market policies are consistent with effective antipoverty programs does not confront the class structures and global capitalist interests bound up with the reproduction of mass poverty in the third world. The World Bank's subordination of the basic needs of the poor to free-market adjustments and reforms in fact suggests that the real purpose of its "two-part strategy" is to ensure continued extraction of surplus from third world countries by maintaining the basic structure of imperialist underdevelopment. PMID- 1917208 TI - Health policy reform in the People's Republic of China. AB - With very limited resources, China has developed perhaps the world's largest network of health care services. The health status of its peoples has risen dramatically during the past 40 years. The reasons for these achievements are complex and include an ideology of equity for all citizens, the near universal availability of adequate food, education, housing, jobs, and transport, and the universal availability of accessible and affordable treatment and preventive health services. Despite these achievements China is facing new problems. These include the aging of the population, continued growth of the population leading to ever increasing demands on all sectors of the economy including health services, urban-rural inequalities, low productivity in the health services, lack of legal safeguards for health protection, a continued burden of infectious and endemic diseases, weak infrastructure for prevention and primary health care, and an increasing burden of chronic diseases associated with tobacco smoking and atherosclerotic circulatory diseases and trauma due to traffic accidents and occupational hazards. Decentralized management, financial incentives for health workers, privatization of medical practitioners, health legislation, and changes to health insurance arrangements have been introduced as a means of addressing the issues. The outcomes have been uneven, with little or no improvements in some problems and good progress in others. Changes in the health system appear to be reflecting not only health reform measures but also general economic reforms. PMID- 1917209 TI - A concept of health-financing reform in the Soviet Union. AB - A conceptual framework and a blueprint of the health-financing reform have been proposed to the Soviet Parliament by a group of economists and health policy analysts. The draft law offers a new pattern of health financing that is expected to increase both the volume and quality of medical care through raising additional funds, decentralizing health policies and management, providing medical facilities with higher motivation for productive and cost-effective performance, and creating economic incentives for employees and individuals for better labor conditions, pollution abatement, and healthy lifestyles. PMID- 1917210 TI - Solidarity and AIDS: introduction. AB - Perhaps more than any other disease in recent history, AIDS has taught a cruel and crucial lesson: the constraints on our response to this epidemic are as deep as our denial, as entrenched as the inequities that permeate our society, as circumscribed as our knowledge, and as unlimited as our compassion and our commitment to human rights. Elaborating on these themes, the final three articles in this Special Section on AIDS consider three widely divergent yet intimately connected topics: AIDS in Cuba, AIDS in Brazil, and global AIDS prevention in the 1990s. Together, they caution that if we persist in treating AIDS as a problem only of "others," no country will be spared the social and economic devastation that promises to be the cost of our contempt and our folly. Solidarity is not an option; it is a necessity. Without conscious recognition of the worldwide relationship between health, human rights, and social inequalities, our attempts to abate the spread of AIDS--and to ease the suffering that follows in its wake- most surely will fall short of our goals. Finally, as we mourn our dead, we must take to heart the words of Mother Jones, and "fight like hell for living." This is the politics of survival. PMID- 1917211 TI - Human immunodeficiency virus in Cuba: the public health response of a Third World country. AB - This article describes Cuba's effort to develop a comprehensive program for control of its human immunodeficiency virus (HIV) epidemic. The program consists of multiple interventions, including blood donor screening, a ban on imported blood and blood products, widespread semicompulsory screening of defined and general populations, research and clinical trials on treatment and diagnostic methods, and health education in the press, radio, television, workplace, and schools. The most controversial of the program's measures has been the treatment of HIV antibody-positive persons (both asymptomatic and clinically ill) through what Cubans term a "sanatorial regimen," consisting of admission into an institutional setting where both preventive and curative treatment is offered, and where residents have limited contact with their families, neighborhoods, friends, and the rest of society. The Cuban HIV control program merits studying because of the comprehensiveness of the measures in a poor country; the special experience of screening large, mostly healthy populations; its potential contribution to understanding the natural history of the disease due to the early identification and follow-up of HIV antibody-positive individuals; and the cultural, political, and socioeconomic conditions that give rise to a different epidemiologic profile of the disease and to an apparent societal consensus on the controversial issue of institutional semiconfinement. PMID- 1917212 TI - We are all people living with AIDS: myths and realities of AIDS in Brazil. AB - Although AIDS was expected in Brazil, no serious efforts were undertaken to prevent AIDS from taking root. Irresponsible press and media coverage highlighted the spread of AIDS within the gay community of the United States, creating an aura of immunity in Brazil to what was characterized as a "foreign" disorder. When AIDS did surface in 1983, the official response was to adopt an abstract, inappropriate, and ideological "Western" model, in which only stigmatized "others" and "minorities" were at risk of HIV infection. Brazilian health authorities subsequently downplayed the significance of the sale of contaminated blood in HIV transmission, and likewise ignored the rising rates of AIDS among Brazil's one unarguable majority group: the poor. An analysis of efforts to force the "facts" of AIDS to fit a false model's predictions leads to a clearer definition of the broader context of the Brazilian epidemic: we all are people living with AIDS, precisely because we live in this age of AIDS; it is sheer folly to discriminate against persons infected by HIV and to obstruct their participation in efforts to curtail the epidemic's spread; and the necessary response to AIDS is solidarity, not because it is poetic, but because no other response will suffice. PMID- 1917213 TI - Global AIDS: critical issues for prevention in the 1990s. AB - A review of the first decade of global experience with the struggle against HIV/AIDS suggests that prevention will require both full application of existing approaches and fundamental changes in concepts and values. The critical deeper issues can be grouped under three headings: behavior, societal action, and globalism. Behavior, individual and collective, will be increasingly recognized as the major challenge for public health. However, for purposes of HIV prevention (and other issues) a sufficient understanding of behavior has not yet been developed. At the societal level, the activism of community organizations has shifted the balance of initiative in public health toward the community. The long term implications of this evolution for roles and responsibilities at the community, national, and international levels must be explored. Finally, an understanding of global solidarity, based on respect for human rights and on the objective conditions of the modern world, will be critical for the future capability to deal effectively with HIV/AIDS. In summary, the future of HIV/AIDS prevention and control cannot be separated from the major public health and social issues of our time. PMID- 1917214 TI - A response to Samuel Epstein's article on synthetic bovine growth hormone. PMID- 1917215 TI - The West German health care system: a critique. AB - Several leading health policy staff of the AFL-CIO and major unions met with the Board of Physicians for a National Health Program (PNHP) in May 1990. They described the active discussions currently ongoing within the AFL-CIO Health Care Committee, which is composed of 14 international union presidents and sets AFL CIO policy on health care issues. Some union presidents reportedly favored a single-payer, Canadian-style approach, while others apparently preferred a proposal modeled after the West German system, which preserves a major role for insurance companies. The PNHP Board was emphatic in its preference for the single payer approach. Board member Dr. Vicente Navarro wrote the following letter to the union presidents on the AFL-CIO Health Care Committee detailing his critique of the West German approach. PMID- 1917216 TI - Maternity and parental leave, preschool child care, and tax receipts. PMID- 1917217 TI - An evaluation of the maximal anaerobic capacity in man. AB - Maximal anaerobic capacity, i.e., the maximal amount of energy released by anaerobic processes (Ean max, J.kg-1), has been evaluated from maximal increase of plasma lactate concentration (Lap) in eight male subjects of different physical fitness submitted to supramaximal runs of various intensity performed until volitional exhaustion (temps-limite, tlim). As previously found (2), the interindividual differences of tlim were reduced when exercise intensity was expressed by the anaerobic component of exercise defined as the difference between the overall energy requirement (E, W.kg-1) and maximal aerobic power Eox max, W.kg-1). Within the range of intensity studied, Lap did not vary significantly as a function of E-Eox max. However, the performances achieved by the less fit subjects (group 1) remained lower than those achieved by the more athletic subjects (group 2). Mean Lap were significantly higher in group 2 (17.2 mmol.l-1 than in group 1 (13.7 mmol.l-1. The rate of increase of Lap, defined by the ratio Lap/tlim, was a linear function of E-Eox max. The energy equivalent of plasma lactate accumulation (beta), given by the reciprocal of the slope of the equation describing the relationship Lap/tlim = f(E-Eox max), amounts 56.8 J.kg-1 when Lap is increased by 1 mmol.l-1. The energy released by anaerobic glycolysis was calculated by multiplying beta by mean Lap measured in the two groups of subjects. Assuming that the energy yielded by the anaerobic alactic processes amounts 260 J.kg-1(1), mean Ean max values in group 1 and 2 were found to be equal to 1040 (range:910-1110) and 1240 J.kg-1 (range: 1100-1330), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917219 TI - The reproducibility of the 4 mmol/l lactate threshold in trained and untrained women. AB - Lactate threshold measurements are part of the routine testing done for training and diagnostic purposes. The reproducibility of the 4 mmol.l-1 threshold has, however, rarely been investigated. Twenty-seven untrained and 10 endurance trained females each performed two incremental spiroergometric treadmill tests at 5% grade, with three-minute speed increase intervals. Running speed at the threshold increased from 1.9 to 2.1 m.sec-1 in the untrained and remained constant at 3.4 m.sec-1 in the trained group. Heart frequency and oxygen uptake did not change significantly in either group. The variability of changes between untrained individuals expressed by correlation coefficients was r = 0.63 for oxygen uptake, 0.55 for running speed and 0.42 for heart frequency. These figures for the trained persons were r = 0.61; 0.92 and 0.88 respectively. The higher reproducibility of the anaerobic threshold in trained women supports the high value attached to the anaerobic threshold in training guidance. For untrained women, training recommendations of the basis of treadmill tests must consider treadmill running speed to be 0.14m.sec-1 higher than initially achieved during the first test because of coordination problems. Training-guidance-based heart frequency must take into account a higher variability for untrained than for trained females. PMID- 1917218 TI - A 2-km walking test for assessing the cardiorespiratory fitness of healthy adults. AB - A simple walking test was developed with 159 (females = 80, males = 79) healthy 20-65-year-old subjects. All the subjects first walked the distances of 1.0, 1.5 and 2.0 km on a flat dirt road. Half of the participants were tested in the laboratory for maximal oxygen uptake (VO2max), and the 2-km test was repeated again twice. In a comparison of the three distances, the 2-km test was repeatable, the most preferable subjectively and the most accurate in predicting VO2max. A sex-specific prediction model including walking time, heart rate at the end of the walk, age and body mass index predicted 73-75% of the variance in VO2max (ml.kg-1.min-1) and that with body weight 66-76%, with a standard error of estimate of the order of 9-15% of the mean. The cross-validation of the models yielded reasonable accuracy in obese men and women and in moderately active men, and less accuracy in moderately active women and highly active men. These results suggest that a fast 2-km walk supplemented with simple measurements is a feasible and accurate alternative for determining the cardiorespiratory fitness of healthy adults. PMID- 1917220 TI - Relationship of cardiac size to maximal oxygen uptake and body size in men and women. AB - It has been suggested in previous studies that the difference in endurance performance between males and females is related to gender-specific differences in cardiac function. Other studies have not equated males and females for physical condition, and this may have contributed to the findings. The purpose of this study was to determine the extent to which the difference in VO2max in groups of similarly trained males and females was explained by gender differences in cardiac size, fat-free weight (FFW) and hemoglobin concentration [( Hb]). Measurements of VO2max, FFW, [Hb] and cardiac size (LVM) were made on 19 males and 20 females comparable in age and cardiorespiratory capacity. The difference between men and women in LVM accounted for 68.3% of the gender difference in VO2max, and the combination of LVM and FFW accounted for 98.7% of the gender related difference in VO2max. It was concluded that the gender difference in LVM accounts for a majority of the difference in VO2max in males and females, with other aspects of body size accounting for nearly all the remaining difference. The gender difference in heart size primarily reflects the smaller overall dimensions of women. PMID- 1917221 TI - Physiological comparison of international, national and regional alpine skiers. AB - The purpose of this study was to evaluate the predictive power of physiological tests in categorizing competitive alpine skiers. Sixty-one subjects (30 female and 31 male) were classified into three levels: international, national, and regional on the basis of past competition results. Hydrostatic weighing, maximal cycling, Wingate, 60-s repeated jump, and vertical jump tests were used to assess body composition, aerobic and anaerobic power, respectively. MANOVA revealed a significant group by gender interaction (Hotellings T, p less than .001), and main effects of gender and group (p less than .001). Discriminant analyses performed separately for male and female groups determined which variables were responsible for differences and resulted in selection of the following variables for classification of the men: average work from the repeated jump, absolute power for the vertical jump, and Wingate endurance. For the women, average work from the repeated jump, absolute and relative vertical jump power, absolute maximum Wingate power, and relative repeated jump power were most important. Fat free mass was a powerful predictor for both sexes because of its strong relationship (r greater than 0.85) with power results. Aerobic power was not useful in group classification. In conclusion, physiological tests of anaerobic power and fat-free mass were the best predictors of group membership. PMID- 1917222 TI - Ventilatory threshold and maximal oxygen uptake during cycling and running in female triathletes. AB - Maximal oxygen uptake (VO2max) and the ventilatory threshold (Tvent) were measured during cycle ergometry (CE) and treadmill running (TR) in a group of 10 highly trained female triathletes. Tvent was defined as the VO2 at which the ventilatory equivalent for oxygen increased without a marked rise in the ventilatory equivalent for carbon dioxide. Female triathletes achieved a significantly higher mean (+/- SE) relative VO2max for running (63.6 +/- 1.2 ml.kg-1.min-1) than for cycling (59.9 +/- 1.3 ml.kg-1.min-1). When oxygen uptake measured at the ventilatory threshold was expressed as a percent of VO2max, the mean value obtained for TR (74.0 +/- 2.0% of VO2max) was significantly greater than the value obtained for CE (62.7 +/- 2.1% of VO2max). This occurred even though the total training time and intensity were similar for the two modes of exercise. Female triathletes had average running and cycling VO2max values that compared favorably with maximal oxygen uptake values previously reported for elite female runners and cyclists, respectively. However, mean running and cycling Tvent values (VO2 Tvent as%VO2max) were lower than recently reported values for single-sport athletes. The physiological variability between the triathletes studied and single-sport athletes may be attributed in part to differences in training distance or intensity, and/or to variations in the number of years of intense training in a specific mode of exercise. It was concluded that these triathletes were well-trained in both running and cycling, but not to the same extent as female athletes who only train and compete in running or cycling. PMID- 1917223 TI - Physiological adaptations to concurrent endurance training and low velocity resistance training. AB - This study investigated the effects of concurrent endurances and low velocity resistance training (LVR) on measures of strength and aerobic endurance. One group (ES) performed concurrent endurance training 3 days a week and LVR training on alternate days, 3 days a week for 12 weeks. The other group (S) performed only LVR training 3 days a week for 12 weeks without any endurance training. Measurements and increases in training volume were made every three weeks in both groups. Group ES exhibited increases in submaximal exercise responses after 3, 9 and 12 weeks (p less than 0.05). Knee extension peak torque and total work as well as cross-sectional area of quadriceps femoris were significantly increased after 6 and 9 weeks of training in both groups. These findings indicate that no significant differences in strength gains were observed between subjects performing concurrent endurance and resistance training or resistance training only. However, the time-course of adaptations between groups was somewhat different. PMID- 1917224 TI - The effects of acute moderate exercise on lymphocyte function and serum immunoglobulin levels. AB - The extent and duration of changes on lymphocyte function and serum immunoglobulin (Ig) levels were examined in 12 women who walked 45 min at 60% VO2 max in a laboratory setting. A 2-factor, 2 x 6 design with repeated measures on both factors was utilized. The first factor was condition (exercise and rest), and the second factor was time (six times of measurement over a 24-h period), with treatment order counterbalanced. The 45-min walk, in comparison to rest in a seated position, was not associated with significant changes in circulating numbers of interleukin-2-activated T cells (CD5 and CD25) or on spontaneous or concanavalin-A-stimulated lymphocyte proliferation. A trend for decreased phytohemagglutinin-stimulated lymphocyte proliferation in comparison to the rest condition, however, was seen 1.5 h following the exercise bout (p = 0.047). The patterns of change for serum IgG, IgA, and IgM were significantly different (p = 0.001, p less than 0.001, p = 0.010, respectively) between conditions. IgG rose 7.2% immediately following exercise, and then returned to baseline 1.5 h later, which contrasted significantly with changes in the rest condition. These same patterns of change occurred also with IgA and IgM, but increases immediately following exercise were not significant, although a trend was seen for IgA (p = 0.03). The 45-min walk had no effect on plasma cortisol and epinephrine levels relative to the rest condition, but was associated with a significant 89% increase in norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917225 TI - The relationship between stiffness of the musculature and static flexibility: an alternative explanation for the occurrence of muscular injury. AB - The static flexibility of the gleno-humeral joint of fourteen experienced male weight lifters was determined. Further the subjects performed a series of quasistatic muscular actions of the deltoid/pectoralis musculature during which a brief perturbation was applied. The damped oscillations resulting from such a procedure provided data pertaining to the stiffness of each subject's musculature. A significant correlation (r = -0.544, p less than 0.05) between maximal stiffness and static flexibility was observed. This relationship is discussed with reference to the popular belief that flexibility is related to the incidence of muscular injury. It is proposed that the injury-reducing benefits associated with a high degree of flexibility can be effectively explained through the relationship between flexibility and stiffness. PMID- 1917226 TI - Anabolic steroid use in body builders: an echocardiographic study of left ventricle morphology and function. AB - To ascertain the effect of anabolic steroids (AS) on left ventricle size and function, M-mode and 2D echocardiographic evaluation was carried out in 14 body builders at the end of a phase of AS self-administration (8 +/- 3 weeks, mean +/- S.D.) and after a period (9 +/- 2 weeks, mean +/- S.D.) of drug withdrawal, as well as in 14 other body builders who had never made use of AS, and in 14 sedentary individuals. All the subjects were also examined anthropometrically. Ventricular septal thickness index was slightly greater in athletes using AS, compared to the other two groups (p less than 0.05), while left ventricle mass, the end-diastolic volume indexes and isovolumetric relaxation time, (a parameter of left ventricle diastolic function) were significantly increased (p less than 0.001) as well as the fat free mass (FFM), a marker of skeletal muscle mass. The non-users showed no differences in echocardiographic parameters, compared to sedentary controls. During the off treatment phase, the percentage of adipose mass increased and FFM decreased, while echocardiographic parameters did not vary significantly from on treatment values. The findings indicate that AS can induce an unfavourable enlargement and thickening of the left ventricle, which loses its diastolic properties with the mass increase. These modifications tend to persist following a short period of drug withdrawal. PMID- 1917227 TI - Influence of anabolic steroids on body composition, blood pressure, lipid profile and liver functions in body builders. AB - The effects of anabolic steroids on body composition, blood pressure, lipid profile and liver functions were studied in male body builders who received a weekly i.m. injection of nandrolone-decanoate (100 mg) or placebo for 8 weeks in a double blind way. In addition, 5 body builders received the same dosage of nandrolone-decanoate or placebo, in a double blind cross-over design during two 8 week periods, interspersed by 12 weeks. Anabolic steroids induced a 25-27% decrease in HDL-cholesterol, which was virtually reversed 6 weeks after cessation of drug use. In the SAD group an increase in diastolic blood pressure was observed, which returned to pre-anabolic values approximately 6 weeks after cessation of drug administration. No deleterious effects of anabolic drugs on plasma activity of liver enzymes were found. Increases in lean body mass were found in all groups, though the increase in the subjects who received anabolic steroids was superior to that in the placebo-treated subjects. The increase in lean body mass suggests increases in muscle mass. PMID- 1917228 TI - Diagnosis and treatment of stress fractures located at the mid-tibial shaft in athletes. AB - Anterior mid-tibial stress fractures are a clinical problem. The diagnosis can be delayed because the normal radiographic anteroposterior and side views may only show thickening of the anterior cortex. Oblique views and tomography are often required. Isotope scan confirms the diagnosis and is the method of choice. The treatment varies from rest to operational intervention. A delayed union of this area of the tibia is a potential complication and is a high risk for an athlete, a complete fracture being the most serious complication. We present the results of conservative and operative treatment of 17 patients. Of these cases, nine progressed to a delayed union and operation was performed using transversal drilling with a 2.0-2.5 drill. We recommend a period of rest up till six months and surgical intervention with drilling of the hypertrophied cortex if there is any suspicion of a possibility of a delayed union. Also, if there is a long delay in the diagnosis, operative treatment is recommended. Biopsy is recommended during surgery for differential diagnosis. PMID- 1917229 TI - Anxiety and intense running exercise in the presence and absence of interpersonal competition. AB - The purposes of this study were to evaluate the effects of intense running exercise in the presence and absence of interpersonal competition on both (a) pre exercise anxiety levels and (b) alterations in anxiety as a consequence of the exercise. Seven females and 10 males performed a 5-mile run over the same outdoor course on two separate days. In one condition the subjects ran in a road-race in which intense exercise was combined with interpersonal competition. In the second condition, exercise of the same intensity (84% VO2max) and duration was completed, but interpersonal competition was absent. Cognitive (State-Trait Anxiety Inventory; STAI) and somatic (Body Awareness Scale; BAS) aspects of anxiety were measured 15 min before and after exercise as well as on a separate day under non-stressful, baseline conditions. A main effect for the Trials factor was found using repeated measures ANOVA [Condition (presence/absence of interpersonal competition) X Gender X Trials (baseline/pre-exercise/post exercise)], and post-hoc analysis revealed that post-exercise state anxiety and body awareness levels were both reduced compared to pre-exercise baseline values. Condition and Gender main effects were not significant nor were any of the interaction effects. Pre-exercise STAI and BAS levels were found to be significantly (p less than .01) elevated above baseline values. However, while post-exercise STAI scores were significantly (p less than .01) below the baseline STAI level, the post-exercise BAS values did not fall below the corresponding baseline level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917230 TI - Perception of effort in female and male competitive swimmers. AB - The primary purpose of this investigation was to compare 31 competitive female swimmers with 31 competitive male swimmers on their perceptual responses to submaximal swimming. A secondary purpose was to evaluate the relationship between heart rate (HR) and perceived exertion (RPE) in swimming. Each swimmer completed a 200-yd swim in his/her specialty stroke at 90% of the swimmer's current best time. Underwater and overhead pace lights were used to achieve an even pace during the swims, and HR was monitored by means of radiotelemetry. Ratings of overall and local perceived exertion were assessed immediately following each swim with Borg's 6-20 scale. ANOVA revealed no RPE differences across stroke classifications for the female or male swimmers, but local and overall RPE were lower (p less than 0.01) in the females. Mean HR, however, was significantly higher (p less than 0.05) for the female swimmers. Unlike research with other exercise modes, correlational analyses revealed that overall and local RPE were unrelated to HR (p greater than 0.05). Based on these findings, it is concluded that 1) female swimmers judged a paced swim to be less effortful than did male swimmers despite a greater objective strain in the females, and 2) HR was not correlated with perception of effort. PMID- 1917231 TI - The effects of non-response in a prospective study of cancer: 15-year follow-up. AB - Out of 11,136 Japanese men identified on the island of Oahu, Hawaii in 1965 by the Honolulu Heart Program, 8006 responded to a mailed questionnaire and were examined. Some 1871 responded only to the mailed questionnaire, and 1259 did not respond at all. After 15 years of follow-up, the examined men had significantly lower risk of death from all causes and death from cancer. Minor differences were also noted between the two groups in the risk of cancer of the lung, stomach, colon, and rectum. However, the examined men had a significantly higher risk of prostate cancer. In general, the strength of these non-response effects was mainly due to risk differences in the first five years of the 15-year follow-up period. The relative risk (RR) of each of the seven endpoint events tended towards 1.0 as each of the three successive five-year follow-up intervals were considered. An exception to this was the prostate cancer incidence RR which favoured the unexamined men throughout the entire 15 years, but significantly so only in the last five-year follow-up interval. When the 8006 examined and 1871 unexamined men who responded to the mailed questionnaire were evaluated with respect to the association of cigarette smoking with lung cancer incidence, the RR for smokers was 9.77 for the examined men, and 6.73 for the unexamined men. Since these RRs are not significantly different, there should be little bias in RR estimates of cigarette smoking for lung cancer if the observation was limited to only the examined men. With regard to the association of body mass index (BMI) with colon cancer in older men, the RRs for men in the highest BMI quintile were quite comparable, at 1.37 for the examined group and 1.60 for the unexamined men. We conclude that although some non-response effects on cancer incidence exist in this cohort, they do not appear to be serious enough to have changed conclusions drawn about risk relationships. PMID- 1917232 TI - Socioeconomic differentials in cancer among men. AB - The relationship between cancer and socioeconomic position is examined for men using data from three sources--the Whitehall Study of London civil servants, the OPCS Longitudinal Study and the Registrar General's Decennial Supplement. Mortality from, or registration for, malignant neoplasms was higher overall in lower socioeconomic groups. There was considerable variation in the strength, and to a lesser extent direction, of the association of specific cancer sites and socioeconomic position within each of the studies. However, between the studies the relationships between socioeconomic position and the particular cancers were very similar. The similarity in results, taken in conjunction with the differences in design and methods of the three studies, makes it very unlikely that these consistent associations are due to artefacts. The heterogeneity in relationships between specific cancer sites and socioeconomic position suggests that no single factor--such as differences in general susceptibility or differences in smoking behaviour--can account for these associations. However socioeconomic differentials displayed by a particular malignancy do offer clues to its aetiology, and provide an indication of the scope that exists for reducing the burden of cancer within a population. PMID- 1917233 TI - Who has Pap tests? Variables associated with the use of Pap tests in absence of screening programmes. AB - Characteristics associated with the use of Pap tests were studied in a random sample of 581 women 18-69 years old; residents of Turin, Italy. There has been no organized screening programme in the area. (Tests possibly related to symptoms were not considered). Data were analysed by multiple logistic regression. Some 48% of women had never had a smear. The prevalence of women ever undergoing a Pap test was higher in middle-aged, married and more educated women (p less than 0.001 in all these cases). We found a linear trend (p less than 0.05) related to time since last visit to the family physician. A number of 'preventive' behavioural practices (physical exercise, no alcohol consumption) and experience of early diagnostic procedures for cancer e.g. BSE and mammography, were also associated with ever having had a Pap smear. The prevalence of ever-tested women was significantly lower among lifetime non-smokers than among ex-smokers and current smokers who planned to stop smoking but not lower than in current smokers who did not plan to stop. Results were similar when having had a test within the last three years was taken as the outcome. These results may be useful in planning screening strategies and educational programmes designed to improve attendance in an organized screening programme. PMID- 1917234 TI - Epidemiological evidence for the 'two-disease hypothesis' in Hodgkin's disease. AB - This study relates to 1803 newly diagnosed cases of Hodgkin's Disease (HD) registered between 1984 and 1988 by a specialist leukaemia-lymphoma registry covering approximately half of England and Wales. In addition to registration data the analyses use routine census data. Rye classification is available for the majority of cases with only 7% being unclassified. The data confirm that the young adult peak in HD occurrence is attributable to the nodular sclerosing subtype (NS), and there is some evidence that NS has a different geographical distribution by county to the other Rye subtypes. Because of possible geographical biases in the classification, subsequent spatial analyses are disaggregated by age at diagnosis with particular emphasis being placed on the two age groups 0-34 and 50-79 years. For these, trends of risk by areal socioeconomic status are in opposite directions and the effects of urban-rural status while in the same direction also differ significantly. Allowance for these does not, however, explain the significant difference between the county distributions of the two groups. Patterns of spatial clustering are quite distinct with evidence for local spatial aggregation amongst younger cases. PMID- 1917235 TI - Diet and cancer of the colon and rectum: a case-control study in China. AB - A case-control study was carried out in Harbin city to assess the role of diet in the aetiology of colorectal cancer. A total of 336 incident cases of histologically confirmed colorectal cancer (111 colon cancer and 225 rectal cancer) and an equal number of controls with other non-neoplastic diseases were interviewed in hospital wards. Data concerning the average frequency of consumption and amount consumed of single food items were obtained by a dietary history questionnaire. Odds ratios and their confidence limits were computed. Multiple regression for risk status was also used. Vegetables, particularly green vegetables, chives and celery, have a strong protective effect against colorectal cancer. Reduced consumption of meat, eggs, bean products and grain was associated with increasing risk for cancer of the rectum. Alcohol intake was found to be an important risk factor for developing colon cancer and male rectal cancer. PMID- 1917236 TI - Folate intake and carcinogenesis of the colon and rectum. AB - Experimental evidence suggests that folate depletion plays a role in carcinogenesis. A case-control study examining folate intake was conducted. Some 428 colon and 372 rectal cancer cases with matched neighbourhood controls were interviewed regarding usual intake of foods, including food preparation. Unadjusted folate was not associated with risk of either cancer. Controlling for kilocalories, odds ratios (ORs) for those with the highest folate intake were 0.5 (95% confidence interval (CI): 0.24-1.03) and 0.31 (95% CI: 0.16-0.59) for females and males for rectal cancer. There was no change in colon cancer risk associated with folate intake. There was an indication of an interaction of folate and alcohol intake; the difference in risk associated with low and high folate intake was highest for males in the highest alcohol category. Associations were of similar magnitude for other dietary factors correlated with folate. It appears that intake of folate or a correlated factor may be negatively related to risk of rectal cancer. PMID- 1917237 TI - Are respiratory symptoms and chronic airflow limitation really associated with an increased risk of respiratory cancer? AB - The relationship between respiratory symptoms, chronic airflow limitation and respiratory cancer was examined in a random population sample of 876 middle-aged men. All men were examined in 1974 with interview and lung function tests. Information on respiratory cancer from 1974 to June 1985 was obtained from the Danish Cancer Register. Using a multivariate Cox regression model including age as the underlying time scale and controlling for pack-years of cigarettes, cough and breathlessness were found to be significantly related to cancer--relative risks (RRs) 2.5 (95% confidence interval (CI): 1.3-5.0) and 2.2 (95% CI: 1.0 4.9), respectively. Phlegm, chronic phlegm, and chronic bronchitis were not related to respiratory cancer after controlling for age and smoking. Forced expiratory volume in one second (FEV1) was related to respiratory cancer, RR = 2.1 (95% CI: 1.3-3.4) per litre under the expected FEV1 given height. Thus, our study demonstrates some relationship between respiratory symptoms and FEV1 and respiratory cancer; however, the study at the same time questions the previously demonstrated relationship between phlegm and respiratory cancer. PMID- 1917238 TI - Bias from missing values: sex differences in implication of failed venepuncture for the Scottish Heart Health Study. AB - Missing values are common in epidemiological data, and yet their possible effect on the results of the investigation is seldom quantified despite the fact that they are a likely source of bias. This paper describes a simple method, based on odds ratios, for assessing whether missing values are likely to cause bias, and for quantifying the magnitude of any such bias. The method is applied to the Scottish Heart Health Study, a study of risk factors for coronary heart disease amongst 10,359 men and women. It is found that, although no bias is apparent in the male subjects, females with missing blood samples are twice as likely to have a history of myocardial infarction than other women. Missing blood samples are shown to be associated with increased body mass index and difficult peripheral veins. The bias caused by the missing female blood samples is considerable, with estimated errors of between 4% and 12% in the mean values of total cholesterol, HDL-cholesterol, triglycerides, creatinine, uric acid and fibrinogen. PMID- 1917240 TI - Social class inequalities in the decline of coronary heart disease among New Zealand men, 1975-1977 to 1985-1987. AB - Coronary heart disease (CHD) is regarded as a disease of developed 'western' societies. Within developed societies, however, CHD is typically a disease of the less affluent socioeconomic classes. This has not always been the case. Forty years ago. CHD was reported to be more common among the upper social classes. In New Zealand, as in other developed countries, this original trend across social classes was reversed during the past 40 years. In 1975-1977, a gradient across social class was observed for both CHD and cerebrovascular disease mortality, with the lowest social classes experiencing the highest mortality. This study has now been repeated for the period 1985-1987. Employed males aged 15-64 years were categorized by the Elley-Irving scale into six social classes. The overall age standardized mortality rate from CHD declined over the ten-year period, from 163.0 to 121.7 per 100,000 person-years. Over the same period, however, the social class gradient for coronary mortality actually increased. The overall age standardized mortality rate from cerebrovascular disease also declined over the ten-year period, from 25.9 to 17.7 per 100,000 person-years. A social class gradient for cerebrovascular mortality was present in both periods. In contrast to coronary mortality, however, the social class gradient diminished slightly over the ten-year period. PMID- 1917241 TI - Mortality among urban bus drivers. AB - Driving a bus in urban areas is considered to be a highly stressful occupation, one which also involves exposure to air pollutants generated by motor vehicles. In order to investigate the potential health hazards associated with this occupation, the causes of death of 376 New York City bus drivers were studied. Analyses of proportionate mortality found a significant excess due to ischaemic heart disease in drivers in both races combined (proportionate mortality ratio PMR = 1.23), and among the 58 non-white drivers (PMR = 1.72). A significantly elevated risk of death from mental, psychoneurotic and personality disorders (ICDA Ninth Revision 290-319, which includes alcoholism and narcotics abuse) was also found in the combined group (PMR = 2.66), and among the white drivers (PMR = 3.05). For all drivers, PMRs for all malignant neoplasms (PMR = 1.26) and for cancer of the oesophagus (PMR = 2.54) were significantly elevated. No cancer sites were found to be significantly elevated in the proportionate mortality analyses by race. These findings are consistent with the growing body of literature linking job strain with cardiovascular disease among bus drivers. PMID- 1917239 TI - Edinburgh Artery Study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. AB - Intermittent claudication has been studied in cardiovascular surveys but limited information is available on asymptomatic peripheral arterial disease. The purpose of this paper is to describe the prevalence of both asymptomatic and symptomatic disease and relation to ischaemic heart disease in the Edinburgh Artery Study. A cross-sectional survey was conducted on an age-stratified sample of men and women aged 55 to 74 years selected from age-sex registers in ten general practices in the city. Arterial disease was assessed in 1592 participants by means of the WHO questionnaire on intermittent claudication and measurement of the ankle brachial systolic pressure index (ABPI) and change in ankle systolic pressure during reactive hyperaemia. The prevalence of intermittent claudication was 4.5% (95% confidence interval (CI): 3.5%-5.5%). Major asymptomatic disease causing a significant impairment of blood flow occurred in 8.0% (95% CI: 6.6%-9.4%). A further 16.6% (95% CI: 14.6%-18.5%) had criteria considered abnormal in clinical practice: 9.0% had ABPI less than 0.9 and 7.6% had reactive hyperaemia pressure reduction greater than 20%. Intermittent claudication was equally common in both sexes. The ABPI and reactive hyperaemia results suggested a slight preponderance of asymptomatic disease in males and were consistent with an increasing prevalence with age and lower social class. Mean ABPI was higher in normal men than women, and was lower in the left leg than the right suggesting a unilateral predisposition to disease. Subjects with major asymptomatic disease had more evidence of ischaemic heart disease than in the normal population (relative risk (RR) 1.6; 95% CI: 1.3-1.9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917242 TI - Cigarette smoking and birthweight: type of cigarette smoked and a possible threshold effect. AB - The effects on birthweight of the number of cigarettes smoked and their tar, nicotine and carbon monoxide yields were investigated prospectively in 1309 pregnant women of whom 414 were smokers. Several approaches to modelling the effect of smoking were tried. These suggested that while both yield and quantity smoked were important, yield had the greatest effect. This led to an empirical approach whereby consistent smokers were divided into four categories according to whether they smoked a low or high quantity of cigarettes per day and whether they smoked low or high yield cigarettes. Using these four groups it emerged that women smoking a low quantity of low yield cigarettes had babies of a similar mean birthweight to those of non-smokers whereas those smoking a low quantity of high yield cigarettes had babies whose birthweight was reduced to the same degree (6% or more) as those of mothers who smoked higher quantities. This apparent threshold was estimated as 13 cigarettes/day and 15 mg/cigarette carbon monoxide. We conclude that brand smoked is at least as important as quantity and that in this population there is evidence for a threshold for tobacco smoke intake below which no discernible effect on birthweight is seen. PMID- 1917243 TI - Comparison of smoking prevalence in school students sampled from the United States of America and the Union of Soviet Socialist Republics. AB - To assess the smoking prevalence among adolescents in the USA and the USSR, students in Moscow and Minneapolis were surveyed by common protocol and identically trained staff. Smoking habits were measured by a self-report questionnaire and an expired air sample of carbon monoxide (CO). Significant gender differences were found between the two national groups. Among girls in the USA, there was a significantly higher rate of weekly smoking as compared to girls in the USSR. Among boys in the USSR as compared to those in the USA, there was a significantly higher rate of ever smokers and daily smokers, but also of ex smokers. These gender differences may reflect cultural differences in smoking patterns between the two countries. Cigarette smoking is clearly a public health problem in both countries with its onset in adolescence. PMID- 1917244 TI - Combined effect of grain farming and smoking on lung function and the prevalence of chronic bronchitis. AB - The combined effect of grain farming and smoking on lung function and the prevalence of chronic bronchitis was examined in 1633 residents 20 to 65 years of age from the town of Humboldt, Saskatchewan. Multiple multivariate analysis indicated that in women grain farming and smoking had a significant synergistic effect on the values of forced expired volume in one second/forced vital capacity (FEV1/FVC), mid-expiratory flow rate (MMFR), flow rate at 50% and 25% of total volume (Vmax50 and Vmax25) after adjustment for covariates including age and height. No other factors were found to change the results. The combined effect of grain farming and smoking on lung function was not statistically significant in men. The data also show that female non-smoking grain farmers had an identical prevalence of chronic bronchitis compared with non-smoking female non-farmers, 2.0% versus 2.1%. But in women with a positive smoking history, the prevalence was 13.2% and 5.9% respectively, giving an adjusted odds ratio in grain farmers compared to non-farmers of 3.55 (95% confidence interval (Cl): 1.06-11.30). It was found that the prevalence of chronic bronchitis increased more rapidly with increasing cigarette consumption in grain farmers than in non-farmers in women. It was estimated that 85%, 72% and 66% of the prevalence of chronic bronchitis was attributed to the joint effects of grain farming and ex-smoking, light smoking (1-19 cigarettes/day) or heavy smoking (20+ cigarettes/day) status, respectively. In contrast to women, the effect of grain farming on the prevalence of chronic bronchitis was similar in men with and without a positive smoking history. Our data suggest that there is a positive interactive effect of grain farming exposure and smoking on lung function and the prevalence of chronic bronchitis in women. The difference in the interaction between men and women requires further study. PMID- 1917245 TI - Indoor air pollution exposure and lower respiratory infections in young Gambian children. AB - In a rural population-based cohort study of approximately 500 Gambian children under five years old followed for one year, incidence of acute lower respiratory infections (ALR) was related to various risk factors including parental smoking and regular carriage on the mother's back while cooking, a proxy measure for exposure to smoke from cooking fires. Two statistical analyses using a 'child weeks at risk' approach were carried out, including and excluding multiple disease episodes in the same child. Weekly surveillance for ALRI found 75 episodes in 62 children. Stratified analyses using both approaches suggested father's smoking, and, for girls only, carriage on the mother's back while cooking and being part of a polygamous family were the main risk factors associated with infection: when multiple episodes occurring in the same child were excluded, not having a health card was an additional risk factor in children over a year old. Multiple logistic regression modelling of data from both approaches, including each of these risk factors and sex, age, village and season, suggested father's smoking, carriage on the mother's back while cooking and being part of a polygamous family increase risk of ALRI, the latter two for girls only. The analysis excluding multiple episodes in the same child also suggested that not having a health card is a risk factor for children aged 1-5 years. The difficulties in interpreting these findings are discussed. PMID- 1917246 TI - Smoking habits and risk of benign breast disease. AB - The relationship between smoking habits and the risk of benign breast disease (BBD) was analyzed using data from a case-control study conducted between 1981 and 1983 in the greater Milan area, Northern Italy. Cases (n = 288) were women with histologically confirmed BBD (203 dysplasia, 85 benign tumours) referred to the National Cancer Institute of Milan for biopsies. Controls were women (n = 291) seen on selected days for a cytological smear for cervical cancer in outpatient clinics of the same Institute. No consistent association emerged between various indicators of smoking habits (smoking status, number of cigarettes smoked per day, duration of smoking) and the risk of BBD. Compared with never smokers the relative risk (RR) of all BBD combined was 0.7 (95% confidence interval, Cl: 0.4-1.3) in exsmokers, 1.4 (95% Cl: 0.8-2.5) in smokers of less than 10 cigarettes per day, and 1.1 (95% Cl: 0.7-1.7) in smokers of 10 or more cigarettes per day. There was some suggestion that the risk may be below unity post-menopause, but the relative risks for smokers were not statistically different in pre- (RR = 1.2; 95% Cl: 0.8-1.8) and post-menopausal (RR = 0.6; 95% Cl: 0.2-1.7) women. The risk of benign tumours (chiefly fibradenoma) was higher in current smokers, but this finding was not statistically significant (RR = 1.5; 95% Cl: 0.9-2.6) and the highest risks were observed in the strata of lighter smokers and those with shorter duration of smoking. Overall these results fail to support a negative association between smoking habits and benign breast disease. PMID- 1917247 TI - The relationship between socioeconomic factors and pulmonary tuberculosis. AB - The role of socioeconomic factors for the risk of developing tuberculosis (TB) is unclear. Differences and similarities between cases and controls on various socioeconomic factors were determined. Some 84 black TB patients on ambulatory treatment and 84 disease-free controls living in the same urban area (South Africa) and matched for age and sex were studied. VARIABLES MEASURED: demographic details, general living conditions, household ownership of luxury items, and weekly consumption of four proteins (meat, fish, chicken and cheese). Three socioeconomic indices were constructed from the above variables. No significant differences were found between cases and controls on most of the variables. Overall significant differences were found on the pattern of language groups (chi square; p = 0.031), employment groups (chi-square; p = 0.029) and meat (chi square; p = 0.012) and chicken consumption (chi-square; p = 0.034). A tendency was observed for more employed cases than controls to have a primary school education. However, no conclusive evidence was found on the association between socioeconomic factors and risk of developing TB. The development of a more appropriate socioeconomic measure for developing countries is a necessary step for further research. PMID- 1917249 TI - The use of 'spot' measurements in epidemiological studies of the health effects of magnetic field exposure. AB - In several countries, epidemiological studies are being planned, or are in progress, to test the hypothesis that a causal relation exists between exposure to extremely low frequency magnetic fields and cancer incidence. One of the major difficulties in these studies is the development of valid and efficient protocols to assess magnetic field exposure. In studies focusing on residential magnetic fields, many researchers are turning to recently developed stationary automated magnetic field monitors to characterize exposure. We argue that a relatively small number of manually collected 'spot' measurements may be an adequate alternative which has several advantages. We compared a dichotomous exposure classification based on continuous magnetic field monitoring of 40 houses with that obtained through 'spot' measurements randomly sampled from the continuous records. We found that a single spot measurement had at least an 80% chance of classifying houses correctly and that this probability did not increase significantly as the number of readings was increased. We also calculated the sensitivity and specificity of various simulated measurement protocols and, from these, the effect of misclassification on estimates of relative risk. Since relatively large spatial variations in background magnetic field exist in many homes, we suggest that a small number of readings collected manually at several points within a residence may characterize the magnetic field better than continuous monitoring at one fixed location. PMID- 1917248 TI - Familial transmission of alcohol use: IV. A seventeen-year follow-up on the relationships between parent and adult offspring alcohol use; Tecumseh, Michigan. AB - The sample for this study comprised 190 three member sets of father, mother, and adult son or daughter who were first interviewed in 1960 as part of Cardiovascular Examination I of the Tecumseh Community Health Study. At that time, alcohol data were collected from self-reports for both parents and offspring. In 1977 alcohol data were again collected for the adult offspring only, from self-reports. In 1960 offspring's drinking was significantly related to both fathers' and mothers' drinking and remained so in 1977 despite shifts over time in the proportions of offspring across five alcohol use categories. The majority of offspring did not fall into their parents' category, but the mode by and large reflected the parent category. The majority of offspring of non drinkers did drink, but at low and not high volume; the majority of offspring of high volume drinkers drank at lower levels than their parents, and were not likely to be life-long abstainers, although they may have become past drinkers. Two non-drinking parents reinforced non-drinking in their adult offspring and two drinking parents reinforced the early onset and persistence of high volume drinking. Among offspring who changed their drinking level between 1960 and 1977, those who had drunk less than their parents were the most likely to have increased their drinking, and those who had drunk more than their parents were the most likely to have decreased their drinking. Patterns observed in this study may be viewed as intrafamilial sources of drinking stability transmitted across generations in a single community. PMID- 1917250 TI - Risks of delivery during the 20th to the 36th week of gestation. AB - Using routinely collected maternity discharge data from 250,000 women in Scotland, we examined the risks of late spontaneous abortion and preterm delivery during the period 20 up to 36 weeks of gestation. Gestational age is treated as a fetal survival time and the risks of delivery associated with a history of spontaneous abortion, induced abortion and perinatal death are examined in a survival model controlling for several demographic and socioeconomic variables. The main objective of the study is to identify factors which are associated with high relative hazard of delivery early in the period, but with decreasing relative hazard of delivery as pregnancy progresses. The factor most clearly associated with converging hazards is a history of two or more spontaneous abortions, and this may reflect the tendency to repeat pregnancy outcome. PMID- 1917251 TI - Levels and determinants of early neonatal mortality in Natal, northeastern Brazil: results of a surveillance and case-control study. AB - An institution-based surveillance and nested case-control study was conducted in Natal, Northeastern Brazil to estimate the level and determinants of early neonatal mortality. The early neonatal mortality rate was 25.5 per 1000 live birth, 75% of early neonatal deaths were premature low birthweight infants, and the mortality rates were 591 and 318 per 1000 respectively, for preterm small for gestational age (PT-SGA) and preterm appropriate for gestational age (PT-AGA) infants. Mortality was 50 per 1000 for term low birthweight, and 8.6 for term normal birthweight AGA infants. In addition to prematurity and low birthweight, the main risk factors associated with early neonatal death were maternal smoking, complications during pregnancy or intrapartum, and inadequate antenatal care. The associations were weaker for prepregnancy factors such as single marital status or low maternal body weight, and no significant associations were observed with socioeconomic status. These findings suggest that in this population, efforts to reduce early neonatal death should focus on improved maternal care and the prevention of prematurity. PMID- 1917253 TI - The spread of human immunodeficiency virus type 2 into Europe: a geographical analysis. AB - Geographically-related computer databases on the global incidence of HIV-1 and HIV-2 infection are being maintained in the Department of Geography at the University of Cambridge, England. Using the information they contain, the original geographical heartlands of HIV-2 infection are identified as former Portuguese and French colonies in West and South Central Africa. The same databases permit the reconstruction of the diffusion corridors by which the virus is spreading from these heartlands into Europe. The reconstruction shows that, as a result of traditional links with their former colonies, the main areas of infection in Europe are Portugal and France. These countries have subsequently acted as diffusion nodes for the spread of the virus to other parts of Europe. The patterns of spread thus differ fundamentally from those by which HIV-1 infection arrived in and is moving through Europe. PMID- 1917252 TI - Childhood mortality among users and non-users of primary health care in a rural west African community. AB - To evaluate the effectiveness of primary health care (PHC) interventions implemented through the Pahou PHC Project, the utilization of PHC by 74 children aged 4 to 35 months who died in 1986 or 1987 was compared to that of 230 controls who survived and were individually matched by date of birth, sex and place of residence. The crude death rate was 35.9/1000/year. Measles vaccination before the first birthday significantly reduced the risk of mortality (Relative Risk/RR = 0.4). Children with less than 75% weight for age early in 1986 had an increased risk (RR = 4.3). Children who died had had significantly fewer contacts with the village health worker (VHW) in the last six months prior to death (RR = 0.3). A similar association was not observed for periods more than six months prior to death. Children who had more regular contact with the VHW throughout life were better protected than children for whom contact had been less systematic. We conclude that VHWs contribute to a better survival of young children through regular personal contact with the household. PMID- 1917254 TI - Rising trend of reported primary genital syphilis and genital ulcer disease in Burkina Faso. AB - Recent trends in reported primary genital syphilis and genital ulcer disease (GUD) were assessed in Burkina Faso using incidence data reported to the Ministry of Health. From 1978 to 1983 the yearly reports of genital syphilis and GUD rose by 42%. A single period moving average was calculated for each consecutive 13 week period from 1978 to 1983, documenting an average 7% rise per year. Severe limitations in the Ministry of Health of personnel and other resources for surveillance were noted and no improvements in surveillance methods were evident during this study. The rising trend suggests a growing problem of ulcerative sexually transmitted diseases, which may, in turn, facilitate infection with sexually acquired human immunodeficiency virus, coincident with the expansion of this epidemic in Africa. Syphilis complications are also almost certain to include adverse pregnancy outcome due to maternal syphilis. The rising trend in genital syphilis and GUD, and the probable increase in associated adverse sequellae, require that prevention and control of sexually transmitted diseases should be made a high priority. PMID- 1917255 TI - Household clustering and intra-household transmission patterns of hepatitis B virus infection in South Africa. AB - The objective of this study was to investigate household clustering of hepatitis B virus (HBV) infection in South Africa in order to understand intra-household patterns of virus transmission that would provide information on potential risk factors of HBV infection. Subjects were the household contacts of 28 hepatitis B surface antigen (HBsAg) positive children (index-carrier), 22 hepatitis B surface antibody positive children (index-past-infection) and 35 children with no serological evidence of HBV infection (index-negative). Evidence of HBV infection (at least one positive HBV marker) was present in 73.7%, 48.7% and 38.2% and HBsAg was present in 19.9%, 8.7% and 2.9% of household contacts of index-carrier (N = 186), index-past-infection (N = 150) and index-negative (N = 207) children respectively. The clustering of HBV infection and HBsAg was present in all subgroups of household contacts regardless of the degree of relatedness to the index child. As age increased, the cumulative prevalence of HBV infection increased while the likelihood of being HBsAg positive decreased. Regardless of age, males were more likely (p less than 0.01) than females to be HBsAg positive. We conclude that HBV infection clusters in households; that there is an increased susceptibility, which is probably not genetically mediated, of becoming an HBV carrier in certain households and that males are at greater risk of being HBV carriers. Intra-household horizontal person-to-person transmission, the precise mechanisms of which are not known, is important in South African blacks. PMID- 1917256 TI - Severity of measles and cross-sex transmission of infection in Copenhagen 1915 1925. AB - Using data on children hospitalized with measles in Copenhagen in 1915-1925, it was found that secondary cases infected at home by someone of the opposite sex had a relative case-fatality rate risk (RR) of 1.52 (95%, confidence interval (Cl): 0.80-2.88) compared with secondary cases infected by someone of the same sex. Males infected by a girl suffered more severely than when infected by another boy (RR = 2.46; 95% Cl: 1.00-6.04) whereas there was no difference for girls. In households with two cases of measles, case fatality was significantly higher in families with a boy and a girl infected at the same time compared with families with two boys or two girls (RR = 1.89; 95% Cl: 1.06-3.37). There was no difference in mortality in families with two boys or two girls having measles at the same time. These results strengthen previous observations from Guinea-Bissau that close contact with a child of the opposite sex increases the severity of measles infection. PMID- 1917257 TI - The protective effect of measles vaccine under routine vaccination conditions in Dar es Salaam, Tanzania: a case-control study. AB - A case-control study was conducted to determine the protective effect of measles vaccine under routine vaccination conditions in Dar es Salaam, Tanzania. A total of 172 cases of measles were obtained over two six-week periods from hospitals likely to admit such cases in the city and their mothers interviewed using a questionnaire that had been developed for the purpose. In addition, each case was matched to four controls for age, sex and place of residence and their mothers were also interviewed using the same questionnaire as for the cases. Vaccination status of the cases and the controls was ascertained by asking the mothers as well as obtaining vaccination information from the Mother-and-Child or Road-to Health (MCH) clinic cards normally issued to mothers at first vaccination of their children. The overall protective effect of measles vaccine in all age groups studied was found to be 54% (95% confidence limits (CL)36%-67%) when mothers' recall for vaccination status was used. This level of protection was considered to be low compared with the efficacy of the vaccine under experimental conditions in controlled trials previously reported. However when MCH Clinic cards were used to ascertain vaccination status the protective effect rose to as high as 96% (95% CL 83%-99%). Potential biases in the study design and their role in masking or exaggerating the vaccine efficacy are discussed. It was therefore concluded that the protective effect of measles vaccine under routine vaccination conditions prevailing in Dar es Salaam region at the time of this study was as high as observed under experimental conditions when ascertainment of vaccination status was record-based. The study therefore recommended that, whenever in doubt about vaccine efficacy, simple study designs like the case-control method should be used to quickly evaluate vaccine efficacy by utilizing record-based vaccination status ascertainment methods. PMID- 1917258 TI - Cluster survey for poliomyelitis and neonatal tetanus in Ilorin, Nigeria. AB - The incidence of poliomyelitis and neonatal tetanus in Ilorin Local Government Area was estimated using a 40-cluster, retrospective survey of neonatal tetanus deaths and lameness from poliomyelitis in March and April 1988. The survey identified 19 neonatal tetanus deaths among 1601 livebirths, giving an incidence rate of 14.9/1000 livebirths. Some 31 residual paralytic polio cases were identified among 4576 children aged five to nine years, giving a prevalence rate of 6.8/1000 children in this age group and an annual incidence rate of 38.3/100,000 general population. Immunization of pregnant women with tetanus toxoid, had a greater impact on mortality from neonatal tetanus than delivery in hospital or birth at home attended by a traditional birth attendant. Antenatal coverage with two doses of tetanus toxoid was 62.6%. Poliomyelitis and neonatal tetanus still constitute important causes of childhood morbidity and mortality in Ilorin and antenatal tetanus immunization coverage is not yet sufficient to control neonatal tetanus in this population. The target age for immunization with tetanus toxoid should be extended to include all women of childbearing age. Further retrospective surveys from other Nigerian states are needed to determine the magnitude of the neonatal tetanus problem throughout the country. PMID- 1917259 TI - Risk factors of neonatal tetanus in Senegal. AB - A case-control study for evaluating the risk factors of neonatal tetanus was conducted in a rural area of Senegal under demographic surveillance (Niakhar). Some 45 neonatal tetanus deaths that occurred in the study area between March 1983 and March 1986 were investigated. They were matched with 187 controls. Neonatal tetanus accounted for one-third of all neonatal deaths; mortality from neonatal tetanus was 16/1000 livebirths. The effect of various demographic, socioeconomic, epidemiological and behavioural factors was investigated in a multivariate analysis using linear logistic regression. There was no difference associated with socioeconomic factors between cases and controls. Factors associated with the skill and behaviour of birth attendant and mother were highly significant and were associated with high odds ratio (OR) and included whether the hands of the person cutting the cord were washed with soap (OR = 5.22; p = 0.001); whether the person who dressed the cord was skilled (OR = 4.71; p = 0.012); whether the age of the mother was less than 18 years (OR = 7.03; p = 0.027) and whether the birth attendant arrived before delivery (OR = 4.15, p = 0.023). Conversely, the type of tool used to cut the cord did not have a significant effect (p = 0.239). Data analysis suggests that a main source of Clostridium tetani may be the hands of the birth attendant and that the main mode of contamination may be the dressing of the wound stump. Results suggest that teaching mothers and birth attendants simple hygienic principles and basic techniques may have a significant impact on neonatal tetanus mortality. PMID- 1917260 TI - Water supply, sanitation and diarrhoeal disease in Nicaragua: results from a case control study. AB - A case-control study of risk factors for child diarrhoeal disease was undertaken in a rural area of Nicaragua. Some 1229 children under the age of five were matched with an equal number of children of the same age presenting with other illnesses unrelated to water and sanitation. The main types of water supply were sampled at monthly intervals and tested for the presence of faecal coliforms in order to characterize their microbiological quality. In spite of marked differences in water quality between the different types of water supply, no relationship was found with diarrhoea morbidity. In contrast, there was a statistically significant association between water availability and diarrhoea morbidity. Children from homes with water supplies over 500 meters from the house had incidence rates of diarrhoea 34% higher than those of children from houses with their own water supply. Owning a latrine was not found to be significantly related to diarrhoea morbidity. A mother's level of schooling was inversely correlated with the frequency of diarrhoea in her children. A significant association was also found between the number of children under the age of five living in the house and the incidence of diarrhoea. These effects remained significant after controlling for confounding variables by conditional logistic regression. PMID- 1917261 TI - Compound hygiene, presence of standpipe and the risk of childhood diarrhoea in an urban settlement of Papua New Guinea. AB - Children below five years of age residing in an urban settlement of Papua New Guinea were monitored from May 1987 to July 1988 in an attempt to identify aetiological factors of childhood diarrhoea. Presence of faeces in the compound was associated with a 48% increase (incidence density ratio (IDR) = 1.48, 95% confidence interval (CI): 1.163-1.897) in diarrhoea morbidity whilst the presence of pigs in the compound was associated with a 69% increase (IDR = 1.694, 95% CI:1.317-2.189). The presence of a standpipe in the compound was associated with a reduction in diarrhoea morbidity of 56%. The effect of presence of faeces, animals, and standpipe on the incidence of diarrhoea was not dependent on whether or not mothers were literate. We conclude that any intervention aimed at these factors is likely to reduce diarrhoea morbidity in similar urban ecosystems. PMID- 1917262 TI - Evidence for recent diarrhoeal morbidity as a risk factor for persistent diarrhoea: a case-control study. AB - The association between persistent diarrhoea and 'recent morbidity' defined as that occurring within the two-month period immediately preceding the onset of persistent diarrhoea was investigated in a population-based case-control study in rural North India. In two separate matched case-control analyses children with persistent diarrhoea (cases) were compared to population controls (five controls matched to each case) and acute diarrhoeal controls (three controls matched to each case). After correcting for possible confounding variables, comparing children with persistent diarrhoea and matched population controls, presence of a recent diarrhoeal illness was significantly associated with persistent diarrhoea with an odds ratio (OR) 2.6 (95%) confidence interval (CI): 1.1-7.1; p less than 0.05); during infancy this OR was 5.2 (95% CI: 1.0-31.9; p less than 0.01). Comparing children with persistent diarrhoea to matched acute diarrhoeal controls, presence of recent diarrhoeal illness was associated with an OR of 5.1 (95% CI: 1.3-20.3) in favour of the episode becoming persistent; in infants this OR was 10.4 (95% CI: 1.1-132.4; p less than 0.001). PMID- 1917263 TI - Sociodemographic factors associated with serum anti-Shigella lipopolysaccharide antibodies and shigellosis. AB - The association between various sociodemographic variables and the presence of anti-Shigella sonnei lipopolysaccharide (LPS) antibodies was examined in a random sample (N = 383) of male Israeli conscripts. Of the male conscripts, 190 (49.6%) had pre-existing antibodies against S. sonnei LPS (defined as HA titres of greater than or equal to 1:10 after treatment of sera with 2-mercaptoethanol). Univariate analysis revealed a significant positive association between the presence of humoral anti-S. sonnei LPS antibodies and sociodemographic variables including Eastern origin (p = 0.007), low socioeconomic status (p = 0.0016), and the number of siblings (p = 0.023). When multiple logistic regression was used to control simultaneously for the effects of the other variables, ethnic origin emerged as the strongest correlate of anti-S. sonnei LPS antibodies. On the other hand, the association of the sociodemographic variables in subjects suffering from S. sonnei infection during their military service, was in the opposite direction (p less than 0.001 for both socioeconomic status and ethnicity). These findings suggest differences between subpopulations in acquired immunity to S. sonnei due to differences in exposure to the homologous organism prior to military service. PMID- 1917264 TI - Estimating maternal mortality in Djibouti: an application of the sisterhood method. AB - In many developing countries even crude estimates of the level of maternal mortality are lacking and the prospects of fulfilling this need using conventional sources of vital registration and health service statistics are not encouraging. The constraint this imposes on the effective planning, management and evaluation of the programmes now being launched to reduce these neglected deaths is self-evident. It is less obvious how the majority of developing countries can be expected to meet the call for reliable estimates of maternal mortality by 1995. The sisterhood method provides a means of obtaining population based estimates using household surveys for data collection. This paper describes the application of the method in Djibouti in the context of a rapid multi-purpose household survey in difficult field circumstances. In recent years the reduction of the level of maternal mortality in developing countries has become a priority for both national governments and international agencies. Attention has been drawn to the wide range of levels within and between countries and to the huge discrepancies in the lifetime risk of maternal death for women in the developed compared with the developing world. This risk has been estimated to range from 1 in 19 in West Africa to almost 1 in 10,000 in Northern Europe. PMID- 1917265 TI - Experimental evaluation of the effects of drug information on antibiotic prescribing: a study in outpatient care in an area of Sri lanka. AB - The intervention level of epidemiology is useful for studying effects in health systems research. Due to practical and ethical reasons, it is often difficult to apply experimental methods such as classical randomized clinical trials in the field. However with alternative approaches such as 'randomization by group' some of these problems can be overcome. Drug information has since long been considered as an instrument to influence physicians, however evaluation of its effects is a new field of research. In the present study the impact of drug information on prescribing behaviour was evaluated in an outpatient setting in Sri Lanka. The study included 15 state health institutions (45 prescribers) with a common drug formulary. Groups of prescribers were randomized into two interventions; newsletters and newsletters reinforced by a group seminar, and one control group. The target topic was 'rational prescribing of antibiotics'. Some 18,766 randomly selected outpatient drug prescriptions were studied. Antibiotics (and sulphonamides) were prescribed to 33.2% of the patients. An overall trend towards a decrease in proportion of patients prescribed antibiotics in the two intervention groups was seen, although the difference was not significant (p greater than 0.05) compared to the control group. This is similar to the effect of written information on prescribing in other studies. A mean difference of 7.4% in written, -7.3% in written + seminar and -0.4% in the control group was shown. The general antibiotic prescribing pattern did not change in any of the three groups. Penicillin was the most commonly prescribed antibiotic and tetracycline was only rarely prescribed to children. This experiment indicates the feasibility of drug information intervention studies in developing countries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917267 TI - Guidelines on ethics for epidemiologists. PMID- 1917266 TI - Comparison of linear and exponential multivariate models for explaining national infant and child mortality. AB - Product form multivariate regression models (multiplicative exponential) were developed with infant and child mortality as outcomes, and national economic, health, nutrition, education, and demographic statistics as predictor variables. The models were applied to data from 129 countries, resulting in R-square values for the product form models of infants and child mortality of 0.77 and 0.80. For comparison purposes, more conventional sum form models (additive linear) were also estimated, and yielded R-square values (0.22, 0.29) markedly lower than the product form models. The product form models also had a much more uniform distribution of residuals and provided improved model fit across the different categories of nations. An inherent advantage to the product form models is that they did not predict negative mortality rates, in contrast to the sum form models which did predict negative mortalities for some of the more developed nations. Using a product form model, the correlation between physicians per capita and infant mortality was shown to be negative rather than positive--thus correcting for an anomaly seen in previous studies which showed a positive correlation between physicians per capita and infant mortality. PMID- 1917268 TI - Computer based indices of body mass and overweight. PMID- 1917269 TI - Psychiatric history and related exposures as risk factors for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. AB - Data from case-control studies of Alzheimer's disease (AD) were pooled to examine the possible roles of history of depression, anti-depressant treatment and adverse life events as risk factors. History of depression was found to be associated with AD, although the effect was confined to late onset cases. The association held for episodes of depression more than 10 years before AD onset, as well as for episodes occurring within a decade of onset. No association was found with anti-depressant treatment. However, data were only available from two studies, limiting the power of the analysis. Also, no association was found with the three major life events considered in the pooled analysis: death of spouse, death of a child and divorce. PMID- 1917270 TI - The EURODEM collaborative re-analysis of case-control studies of Alzheimer's disease: implications for clinical research and practice. AB - The EURODEM re-analyses of 11 case-control studies of Alzheimer's disease imply that familial aggregation of dementia, Down's syndrome, and parkinsonism occurs more frequently in Alzheimer's disease than in matched controls. Prior history of head trauma, hypothyroidism, and depression also occurs in higher frequency among patients with Alzheimer's disease. Exposure to a series of other medical conditions and environmental toxins was not significant. The association between Alzheimer's disease and maternal age remains unclear. PMID- 1917272 TI - Chronic chorioamnionitis: a clinicopathologic study of 17 cases. AB - The clinicopathologic features of 17 cases of an unusual variant of chorioamnionitis distinguished by a pure or predominantly chronic inflammatory infiltrate in the fetal membranes rather than the usual acute inflammatory reaction are reported. In six cases, there was an equal (one case) or minor (five cases) component of acute inflammation in the fetal membranes as well. Concomitant villitis, found in 11 cases, was almost uniformly lymphohistiocytic and destructive, but it varied greatly in severity. Immunoperoxidase stains for cytomegalovirus, herpes simplex I and II, and Toxoplasma gondii; Warthin-Starry, Gomori methenamine silver, Dieterle, Gram and acid fast stains; placental or amniotic fluid culture; and limited maternal serologic studies failed to identify a specific infectious etiology in any case. Seven women had experienced at least one previous spontaneous abortion, fetal death in utero, or preterm birth. No patient reported a history of fever, rash, or flu-like syndrome during pregnancy. Serious antenatal complications were numerous. Preterm birth occurred in 13 cases. Gestational age ranged from 25 to 42 weeks (mean 32 weeks) and birth weight ranged from 740 to 3,230 g (mean 2,100 g). When expressed as a percentile for gestational age, 47% of infants had a birth weight at or below the 25th percentile, and 76% were at or below the 50th percentile. Two infants were born with gross anomalies, and one infant died in the neonatal period. PMID- 1917271 TI - The EURODEM collaborative re-analysis of case-control studies of Alzheimer's disease: implications for public health. AB - In the EURODEM pooling and re-analysis of case-control studies of Alzheimer's disease it has been possible to examine putative risk factors with increased power to detect associations. The fundamental problems of case and control selection persist, such as use of prevalent cases, selection through contact with specific services, difficulties of control choice. Risk factors such as family history and head trauma are shown again, although the biases introduced in collection of exposure data could still account for these findings. Other associations which are shown, such as smoking may be accounted for by factors related to survival and use of prevalent cases. The direct public health implications of these findings are limited. Intervention based on many of the associations found in this re-analysis would have relatively low impact on overall rates of Alzheimer's disease because of the small proportion of the population exposed. The total public health impact of any such intervention would be also limited according to the contribution which Alzheimer's disease makes to overall rates of dementia. Improvement of cardiovascular indices may improve the cerebrovascular status of the population, possibly reducing the incidence of vascular dementia. Other broad strategies to maintain health and function would seem prudent, but specific recommendations to reduce the incidence of Alzheimer's disease, or to slow progression of the disorder cannot be recommended on the basis of these re-analyses. It is clear that more research is needed to understand the risks of different pathologies related to Alzheimer's disease as well as dementia and cognitive change generally in the population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917273 TI - Mast cells in the female genital tract. AB - Mast cells in the human uterus and adnexa have been studied using basic lead acetate fixation and a long toluidine-blue technique to maximise the numbers of cells stained. Counts were performed on measured areas of tissue and the numbers of mast cells related to clinical and pathologic variables. Considerable variation in numbers was found among individual cases at all the sites studied. In the endometrium and myometrium, a drop in the number of mast cells has been demonstrated with advancing age, particularly after menopause. In leiomyomas the highest counts were in the smaller and more cellular lesions. It is concluded that the numbers of mast cells are at least partly related to the degree of cellularity or atrophy of the surrounding tissues. No significant association was found with menorrhagia or with the presence of leiomyomas. PMID- 1917274 TI - Further studies of lectin binding by villous and extravillous trophoblast in normal and pathological pregnancy. AB - Examination of human pregnancy tissues with a panel of lectins provides the opportunity to probe different aspects of carbohydrate structure. Nine biotinylated lectins [concanavalin A (con A), wheat germ agglutin (WGA), Lens culinaris A (LCH-A), Pisum sativum (PSA), Phaseolus vulgaris (PHA-E and PHA-L), Ulex europaeus 1 (UEA1), Griffonia simplicifolia (GSI and GSII)] were used to investigate the lectin binding of human trophoblast in normal, tubal, and molar pregnancy. All lectins except UEA1 bound to normal villous syncytiotrophoblast. Binding of lectins to extravillous trophoblast was more restricted than to villous trophoblast, occurring predominantly with con A, PHA-E, PHA-L, WGA, GSI, and GSII. LCH-A reacted with cyto-trophoblastic columns but not with interstitial or endovascular trophoblast. Con A and GSII were the only lectins that bound to trophoblastic giant cells. GSI and GSII bound preferentially to extravillous trophoblast, showing only focal reactivity with villous trophoblast. Lectin binding in ectopic pregnancy was similar to that in normal first-trimester intrauterine pregnancy. Reactivity in molar pregnancy also generally mirrored that observed in normal pregnancy; however, reactivity of GSII with villous trophoblast was more consistent than that observed in normal pregnancy, and GSI showed uniform binding to proliferating syncytial areas. Thus, lectin binding studies allow definition of surface carbohydrates, which may play a role in the controlled trophoblast proliferation and invasion that occurs in normal pregnancy. PMID- 1917275 TI - Endometrial adenocarcinoma with a component of giant cell carcinoma. AB - We report six high-grade endometrial adenocarcinomas with a malignant giant cell component. The patients ranged in age from 43 to 85 years (mean 65); five were postmenopausal. All the patients presented with vaginal bleeding. The tumors all had a giant cell component that was composed of poorly cohesive sheets and nests of bizarre multinucleated giant cells admixed with an approximately equal number of mononucleate tumor cells. A sarcomatoid pattern and a marked inflammatory infiltrate were each present in three cases. All the tumors contained at least focal areas of endometrial adenocarcinoma of one of the usual types. Occasional malignant giant cells were positive for cytokeratins (AE1/AE3 or CAM 5.2) and epithelial membrane antigen in all three tumors tested. Three tumors were in stage I, one stage III and two stage IV. Two of the patients with stage I disease (each with superficial myometrial invasion) were alive and well 6 and 2 years later. Of the remaining four patients, three died of disease 2.5 years, 6 months, and 5 months after presentation, and one was alive with extensive abdominal disease after 1 year. Giant cell carcinoma of the endometrium is an aggressive tumor that should be distinguished from other endometrial tumors with a prominent giant cell component, including trophoblastic tumors, certain primary sarcomas, and malignant mixed mullerian tumors. It is imperative that malignant giant cells and non-neoplastic giant cells not be confused, as is possible in a curettage or biopsy specimen. PMID- 1917276 TI - Prognostic significance of proliferation in endometrial adenocarcinomas: a multivariate analysis of clinical and flow cytometric variables. AB - In a prospective study, the prognostic significance of clinical and flow cytometric variables was evaluated in univariate and multivariate analyses of 489 cases of endometrial adenocarcinoma. Age, uterine cavity depth, stage, histopathologic grade, myometrial invasion, ploidy level, and S-phase fraction were of prognostic value in the univariate analysis. In a multivariate analysis of clinical variables, age and uterine cavity depth were insignificant. When adding flow cytometric variables (DNA content and S-phase fraction) separately to the clinical variables, the significance of myometrial invasion was reduced, and histopathologic grade became nonsignificant when S-phase fraction was included. When adding both DNA content and S-phase fraction, the DNA content became prognostically insignificant. S-phase fraction was, next to clinical stages III and IV, found to be the strongest predictor of outcome. It is concluded that S phase fraction is a new, objective parameter that can be used for the identification of prognostically different subgroups of patients within a given stage and grade. PMID- 1917277 TI - Cystic adenomatoid tumor of the uterus. AB - We describe a case of cystic adenomatoid tumor of the uterus in a 38-year-old woman. The tumor was a subserosal cystic mass with a maximum diameter of 8 cm and located at the posterior wall of the right cornual region. Histologically, the tumor was composed of multiple cavities lined by flattened cells, lying among thin septa of connective tissue. The neoplasm showed small solid areas with a more typical histologic pattern of adenomatoid tumor. Immunohistochemical techniques showed the cells to be positive for keratins. They showed desmosomes, abundant intracytoplasmic filaments, and microvilli on ultrastructural study. The histologic, immunohistochemical, and ultrastructural characteristics of the present case closely resemble those of benign cystic mesothelioma and strongly support the mesothelial origin of the adenomatoid tumor of the uterus. PMID- 1917278 TI - Ovarian serous tumor with mural nodules of carcinomatous derivation (sarcomatoid carcinoma): report of a case. AB - An ovarian serous cystic tumor of low malignant potential with solid mural sarcoma-like nodules is reported. This tumor metastasized to the ileal wall. The nodules in the ovary and in the ileal wall were made up of highly malignant cells with admixed osteoclast-like multinucleate giant cells. Immunohistochemical reactions demonstrated the epithelial differentiation of the tumor. We propose that the term "sarcomatoid carcinoma" of the ovary should be adopted for these lesions. PMID- 1917279 TI - North American Association for the Study of Obesity and the Society for the Study of Ingestive Behavior. NAASO/SSIB 1991 annual meeting. Sacramento, California, October 20-21, 1991. Abstracts. PMID- 1917280 TI - Centenary biographical note. Wilhelm Noller 1890-1964. PMID- 1917281 TI - Studies on immunodiagnosis of human paragonimiasis and specific antigen of Paragonimus heterotremus. AB - Adult Paragonimus heterotremus were recovered from the lungs and pleural cavity of cats orally infected with metacercariae. The worms were ground and extracted with distilled water. The soluble crude antigen (CA) contained about 40% proteins which could be fractionated by gel filtration on Sephadex G-200 into three profiles namely the F1, F2 and F3. The CA and its Sephadex profiles were used in an indirect enzyme-linked immunosorbent assay (ELISA) for detecting antibodies to P. heterotremus in three groups of patients, i.e. patients whose sputum and/or faeces revealed P. heterotremus eggs (group 1), patients with other parasitic infections (group 2), bacterial proven tuberculosis patients (group 3) and healthy, parasite-free controls (group 4). The sensitivity and specificity of the assay when the F1 was used as the antigen were 100%. Western blot analysis revealed that specific antigen of P. heterotremus was a non-protein component of Mr35 kDa. PMID- 1917282 TI - Ultrastructure of sperm and spermatogenesis of Lobatostoma manteri (Trematoda, Aspidogastrea). AB - Mature sperm has two axonemes of the 9 + '1' pattern incorporated in the sperm body, a row of peripheral microtubules interrupted along part of the sperm by the axonemes, some microtubules in the interior of the sperm and a long lateral extension (lobe) of the sperm body, an elongate nucleus and mitochondrion, and many dense rod-like structures. A supporting rod extends underneath a specialized region consisting of alternating thin and thick transverse rows of irregular dense patches, and with surface ridges around (all or) most of the surface of the sperm. Primary spermatocytes in the prophase of the first meiotic division have synaptonemal complex(es), and are rich in mitochondria. In early spermiogenesis, mitochondria are arranged around the surface of the nucleus, a dense layer appears at one pole of the nucleus, close to an apposed dense layer at the cell membrane in which a row of microtubules develops. The intercentriolar (= central) body develops close to the nucleus. The fully developed intercentriolar body has a regular striation and is located perpendicular and close to the surface of the nucleus. Two flagella extend into the space surrounding the outgoing median process, their basal bodies are located perpendicular to the intercentriolar body and their cross-striated rootlets extend along the surface of the rounded nucleus. At a later stage, rootlets and flagella become more parallel with the intercentriolar body, the nucleus and the fused mitochondria migrate into the median process, and the flagella become incorporated into the median process (= sperm body). The outgrowing spermatozoa are connected to the cytoplasm of the cytophore by dense arching membranes. Finally, rootlets of flagella are resorbed and the spermatozoa are pinched off close to the basal bodies. Two species (Lobatostoma and Multicotyle) of the same family differ strongly in the type of spermiogenesis, although their mature sperm is of the same basic type, i.e. spermiogenesis is not necessarily more useful for phylogenetic considerations than sperm structure. PMID- 1917284 TI - A comparative study of the regenerative processes in a trematode, Philophthalmus gralli, and a planarian, Dugesia dorotocephala. AB - Adults of Philophthalmus gralli, an eyefluke of birds, were laterally amputated mid-way between the anterior testis and the ventral sucker. Worms were sampled at various short time intervals (30 min-6 h) after in vitro culture and long time intervals (1-8 days) after transplantation back to the host. Specimens were fixed for scanning electron microscopy and light microscopy and compared to the planarian, Dugesia dorotocephala, which was laterally transected in the pharyngeal region and maintained in springwater. It was found that wound closure took place by 2 days in the planaria; however, at the end of 8 days wound closure had been initiated but not yet completed in P. gralli. Replacement of major tissues was observed only in D. dorotocephala. Because calcium had been reported to be critical for planarian regeneration, a histochemical stain for calcium distribution was carried out. At the end of the 2-day study, no differences could be found in calcium distribution between the two organisms. No areas of calcium concentration were noted in any tissue important for the regenerative process. PMID- 1917283 TI - Host-finding and host recognition of infective Ancylostoma caninum larvae. AB - A. caninum larvae responded to environmental and host stimuli with four behavioral phases of host-finding. (1) Snake-like movement was stimulated by warmth and by defined vibrations of the substratum. (2) Waving behavior was a prerequisite for the passive change-over to dog hairs. It was stimulated by heat radiation and by the CO2 content, warmth, and humidity of an air stream. (3) Creeping direction: the larvae were attracted by heat in temperature gradients as weak as 0.04 degrees C mm-1 and by dog hydrophilic skin surface extracts, but not by skin lipids or serum. (4) Penetration into agar was stimulated by heat, dog hydrophilic skin fraction, and dog serum. The effective component of serum had a molecular weight of between 5000 and 30,000 and proved to be a protein, since it lost its effectiveness after digestion with proteinases. Dog saliva, urine, milk, and various pure dog serum components did not stimulate penetration. A. caninum larvae were able to penetrate mouse skin repeatedly, but they did not follow the tracks of previously penetrated larvae in agar. PMID- 1917285 TI - Screening of murine monoclonal antibodies against living schistosomula of Schistosoma mansoni by radioimmunoassay. AB - A radioimmunoassay was developed to screen supernatants of murine monoclonal antibodies against surface antigens of living schistosomula of Schistosoma mansoni. Of 196 clones screened, 10% bound schistosomula. Of these, 74% bound only schistosomula. The remaining molecules also reacted with soluble adult worm antigens and soluble egg antigens as determined by enzyme-linked immunosorbent assay. Immunoblot analysis demonstrated that monoclonal antibody 204-3E4 reacted with a 68 kDa protein, a glycoprotein that induces substantial resistance against S. mansoni infection. Recognition of an 18 kDa antigen by 204-3F1 antibody was stage-specific with the antigen being expressed in cercariae, 3- and 24-h-old parasites but not 4-day, lung stage or adult worms. Monoclonal antibody 204-4E3 reacted with purified S. mansoni paramyosin. These data indicate that radioimmunoassay using living schistosomula is a rapid alternative method to identify murine hybridomas that secrete antibodies which react with surface antigens of S. mansoni. PMID- 1917286 TI - Correlation between gut hypersensitivity and resistance to Trichostrongylus colubriformis infection of outbred and inbred lines of guinea pigs. AB - The relationship between gut sensitivity and immunity to challenge infection was examined in outbred and inbred guinea pig lines. Primary infections terminated at 3,6,9 or 13 days and multiple infections of 3 days' duration confirmed the importance of direct gut stimulation and the period of exposure in the induction of immunity and gut hypersensitivity. The studies with the multiple 3-day infections confirmed that the third-stage larvae alone are capable of inducing strong protective immunity and showed that this is accompanied by pronounced gut sensitivity to parasite extracts and secretions. Finally, two inbred guinea pig lines selected for enhanced resistance or susceptibility to T. colubriformis infection displayed corresponding high or low capacities to mount hypersensitivity reactions following a single truncated 3-day primary infection. PMID- 1917287 TI - Effect of Plasmodium berghei infection and chloroquine on the hepatic drug metabolizing system of mice. AB - The hepatic microsomal mixed-function oxidase (MFO) system was markedly impaired during Plasmodium berghei infection in mice. Cytochrome P-450 and other mono oxygenases, viz. aniline hydroxylase, aminopyrine-N-demethylase and benzo(a)pyrene hydroxylase, were significantly decreased while microsomal heme showed a four-fold increase at peak parasitemia (greater than 50%). Oral treatment with chloroquine (16 mg kg-1 body wt for 4 days) of P. berghei-infected mice cleared the parasitemia within 72 h and almost normalized the altered levels of MFO indices, a week after cessation of treatment. The findings were further supported by the isoenzymic profile and drug-binding properties of terminal mono oxygenase, cytochrome P-450. PMID- 1917288 TI - A new methodology for studying parasite specificity and life cycles of trematodes. AB - A new approach to the genome characterization of trematode sporocysts is described to investigate the life cycles of three species of Helicometra and to compare their degree of specificity for mollusc and teleost hosts. PMID- 1917289 TI - Modes of transmission for Ascaris lumbricoides and Trichuris trichiura among Chinese children in Macao City. AB - To obtain more information on the transmission of Ascaris lumbricoides and Trichuris trichiura in Macao City, 308 Chinese children were surveyed. The infection rates of A. lumbricoides and T. trichiura were 14.9 and 6.8%, respectively. There was no association between the infections. A. lumbricoides infection was associated with age and T. trichiura with new immigrants from China. No association was found between the infections and family socio-economic factors. The results suggest that the modes of transmission for A. lumbricoides and T. trichiura may be different in highly urbanized areas. PMID- 1917290 TI - 18S rRNA sequences of Leishmania enriettii promastigote and amastigote. AB - Dideoxy sequencing with reverse transcriptase and universal primers was used to obtain partial sequences of the 18S rRNAs from the promastigote and amastigote life-cycle stages of L. enriettii. Approximately 1400 nucleotides of sequence from the two stages were compared. Unlike Plasmodium berghei, in which 18S rRNAs from the mosquito stage and the mammalian stage of the life cycle are only 96.5% similar, the amastigote and promastigote rRNAs of L. enriettii are identical. In addition, a comparison of 1425 bases of the L. enriettii promastigote sequence with the published sequence of L. donovani revealed only four differences; the two sequences are 99.8% similar. A likely explanation for this high similarity, considering the 97% similarity between L. donovani and the related genus Crithidia fasciculata, is that the two species are closely related and of comparatively recent origin. The low diversity between the 18S rRNA sequences of Leishmania species is similar to that reported for 13 Tetrahymena species, where similarities ranged from 98.1 to 99.9%, but different from the pattern reported in the genus Naegleria, where divergence was greater. PMID- 1917291 TI - Conformation of MeAla6-cyclosporin A by NMR. Relationship of sidechain orientation of the MeBmt-1, MeLeu-9, and MeLeu-10 residues to immunosuppressive activity. AB - MeAla6-cyclosporin A (MeAla6-CsA) is a unique CsA analog that shows weak immunosuppressive activity and yet binds strongly to the proposed cytosolic protein receptor, cyclophilin (CyP). Preliminary 1H NMR data showed significant chemical shift differences between spectra of MeAla6-CsA and CsA, suggesting different preferred conformations. A more detailed study, however, revealed that the backbone conformations of the two molecules are essentially identical, and that the differences can be accounted for, principally, by the sidechain motions of the MeBmt-1, MeLeu-9, and -10 residues. ROE and coupling constant data show that in MeAla6-CsA, the preferred chi 1 rotamers for MeLeu-9 and -10 are + 180 degrees (T), whereas in CsA there is a more even distribution of rotamer populations for MeLeu-10, and a preferred -60 degrees (G-) chi 1 rotamer for MeLeu-9. Similar data argue that the sidechain of MeBmt-1 is more restricted in its motion in MeAla-CsA than in CsA. Temperature studies suggest that these preferred rotamers for MeAla6-CsA may increase the stability of the hydrogen bond between NH(7) and CO(11), but prevent particular residues, especially the essential MeBmt-1 sidechain, from adopting orientations required to elicit immunosuppressive activity. The significant changes observed in the preferred orientations for the sidechains of the MeBmt-1, MeLeu-9, and MeLeu-10 residues in MeAla6-CsA argue that the particular orientations which they assume in CsA are not essential for cyclophilin binding. PMID- 1917293 TI - Conductance measurements in solid phase peptide synthesis. I. Monitoring coupling and deprotection in Fmoc chemistry. AB - Potentiated conductance shows promise for monitoring the progress of both coupling and deprotection reactions in solid phase peptide synthesis using Fmoc chemistry. Sterically hindered base may be added to the aprotic polar solvents used for synthesis, this induces ionisation of acids formed in the coupling and deprotection reactions, thus giving rise to a conductance signal in the solvent. Changes in this signal allow reactions occurring at the resin to be followed with no degradation of coupling efficiency. PMID- 1917292 TI - Biological and conformational studies of [Val4]morphiceptin and [D Val4]morphiceptin analogs incorporating cis-2-aminocyclopentane carboxylic acid as a peptidomimetic for proline. AB - We report the synthesis, biological activity, and conformational analysis of tetrapeptide analogs related to [Val4]morphiceptin and [D-Val4]morphiceptin in which the proline at the second position has been replaced with cis-2 aminocyclopentane carboxylic acid (cis-2-Ac5c). Since the cis-2-Ac5c residue contains a normal amide, only the trans form has been observed about the amide bond between the first and second residues. The cis-2-Ac5c is a beta amino acid with two chiral centers resulting in two possible configurational isomers, namely (1S, 2R) and 1R, 2S) forms. The analogs containing the (1S, 2R)-Ac5c residue show activity at the mu-receptor but are inactive at the delta-receptor, resulting in a high selectivity for the mu-receptor. The (1R,2S)-Ac5c containing analogs are completely inactive at both the mu- and delta-receptors. The conformational analysis indicates that the separation of the aromatic rings of the tyrosine and phenylalanine residues, as expressed by the center-to-center distance, is 10.1 12.7 A for the preferred conformations of the bioactive analogs containing the (1S,2R)-Ac5c residue while a range of 4.8-7.0 A is observed for the preferred conformations of the inactive analogs with the (IR,2S)-Ac5c residue. A comparison of the findings from the conformational analysis and biological assays establishes the fact that a relatively large separation of the two aromatic side chains is required for the mu-opioid receptor activity of these molecules. Since the tetrapeptide amides studied in this investigation show similar biological profiles to those of the morphiceptin-related analogs, we have compared the preferred conformations estimated for the cis-2-Ac5c containing analogs with those of morphiceptin. One of the low energy conformations calculated for morphiceptin with the cis form about the tyrosine and proline residues has considerable topological similarity with the bioactive analogs containing the (1S,2R)-Ac5c residue, indicating that the cis from about these two residues is required for the biological activity of the morphiceptin-related analogs containing the proline at the second position. PMID- 1917294 TI - Heterodetic bicyclic decapeptide cyclo (Glu1-Leu2-Pro3-Gly4-Ser5-Ile6-Pro7- Ala8) cyclo-(1 gamma-5 beta) Phe9-Gly10. Synthesis and 2-D NMR conformational analysis. AB - Bicyclic peptides are useful model molecules that can mimic the constrained local folding of a great number of natural peptides and proteins, such as ionophoric peptides, enzyme active site, and ligand-receptor active site. The synthesis of the bicyclic title compound with the liquid phase method is described with experimental details. Of particular interest is the heterodetic closure of the second ring. The peptide showed a complexing activity with metal cations like Ba2+, Ca2+, and Mg2+. The free bicyclic peptide conformation in solution has been studied by means of NMR spectroscopy and a plausible structure model worked out with model building on NMR constraints is proposed. PMID- 1917295 TI - Hydration of clupeine in solution. AB - Spin-lattice relaxation times, T1, of H2(17) O at 25 degrees were measured for aqueous solutions of clupeine and its constituent amino acids, which are serine, threonine, proline and arginine. The dynamic hydration numbers, nDHN, of clupeine and amino acids were determined from a concentration dependence of T1. The coordination numbers nh, and the rotational correlation times, tau ch, of water molecules around clupeine and amino acids were estimated and compared with that of pure water. The tau ch/tau co of clupeine was 1.85 and close to that of arginine. The experimental value of nDHN of clupeine was in good agreement with that calculated from the nDHN values of the constituent amino acids. This means that the clupeine molecule has a random conformation in solution. PMID- 1917296 TI - Cyclization of disulfide-containing peptides in solid-phase synthesis. AB - Disulfide-containing peptides may be obtained in good yields and purities when oxidations are carried out on peptide chains anchored to polymeric supports used for solid-phase synthesis. Such approaches take advantage of the pseudo-dilution phenomenon which favors intramolecular processes. A variety of procedures have been demonstrated using the related model peptides Ac-Cys-Pro-D Val-Cys-NH2 and Ac-Pen-Pro-D Val-Cys-NH2 (which both readily assume a type II beta-turn conformation that becomes stabilized by a 14-membered disulfide-containing intramolecular ring), and oxytocin (conformationally mobile 20-membered disulfide ring). Both Boc and Fmoc were used for N alpha-amino protection, the beta-thiols of cysteine or penicillamine were blocked by S-acetamidomethyl (Acm), S-9 fluorenylmethyl (Fm), or S-trityl (Trt), and compatible anchoring linkages included HF-labile 4-methylbenzhydrylamide (MBHA), TFA-labile tris (alkoxy)benzylamide (PAL), and photolabile o-nitrobenzylamide (Nonb). Assemblies of linear sequences proceeded smoothly, and polymer-supported oxidations were carried out in a variety of ways either directly or after deblocking to the resin bound dithiol. Chains were released from the support without substantial damage to the disulfide bridges, and overall yields were as high as 60-90%. PMID- 1917297 TI - Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships. AB - The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physiochemical properties contained substantial structure activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physiochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables. PMID- 1917298 TI - Guanidination of a peptide side chain amino group on a solid support. AB - A novel guanidination method of converting a peptide side chain amino group to a guanidino group on a solid support is described. Four guanidinating reagents were evaluated using a model tetrapeptide attached to a polystyrene resin. Experimental data indicate that the two nitroguanidinating reagents, but not the two tosylguanidinating reagents, can be used effectively in solid phase peptide synthesis. PMID- 1917299 TI - Computational analysis of conformational behavior of cholecystokinin fragments. I CCK4, CCK5, CCK6 and CCK7 molecules. AB - A conformational analysis has been performed on several peptide fragments (CCK4 to CCK7) of the cholecystokinin neuromodulator. The Monte-Carlo Metropolis method was used to explore the conformational space of all these flexible units and different electric charge distributions were introduced in order to mimic pH effects. Results agree reasonably well with experimental data from NMR and fluorescence experiments. The CCK4 fragment displays a peculiar conformational behavior when compared to all other longer peptides with short range interaction between the Trp and Phe aromatic side-chains. Several H-bonded conformers including C- or beta-turns are found for CCK5 to CCK7. These findings are correlated to the central and peripheral actions of these compounds and hypotheses concerning the best possible templates for each one are discussed. PMID- 1917300 TI - Transesterification of peptide esters and peptidyl resins in methanol-containing calcium acetate. AB - The following crude peptide derivatives obtained by thermolysin catalysis in the presence of calcium acetate, were dissolved in methanol and in methanol containing calcium acetate to determine the possible occurrence of transesterification: Z-Asn-Leu-Gly-OEt, Boc-Asn-Leu-Gly-OEt, Moz-Asn-Leu-Gly OBzl, Moz-Asn-Leu-Gly-OtBu, Moz-Gln-Leu-Gly-OEt, Moz-Asn-Ile-Gly-OEt, and Moz-Asn Leu-Ala-OEt. Only Z-Asn-Leu-Gly-OEt and Moz-Gln-Leu-Gly-OEt were transesterified in methanol, indicating the existence of a peptide derivative-Ca2+ catalytic complex that may favor the reaction. In the presence of calcium acetate, all protected peptide esters except the t-butyl esters were transesterified. The transesterification of several other di- and tripeptide derivatives of different structures in methanol-containing calcium acetate was detected by HPLC and confirmed by the isolation and characterization of some of the protected peptide methyl esters obtained. Boc-Leu-Gly- and Moz-Asn-Leu-Gly-Merrifield resin were also transesterified in these solutions. PMID- 1917301 TI - A novel reagent, dialkylphosphite, for peptide synthesis. AB - The same dialkylphosphite reagent can be used for both N protection and C activation of amino acids. Two N-diisopropyloxyphosphinyl (Dipp) tripeptide esters were prepared, and nine N-Dipp-dipeptide acids were synthesized through the activated amide intermediate. The positive ion FAB-MS of N-Dipp-tripeptide showed novel cleavage patterns in that only the N-phosphoryl fragment ions gave intense peaks while the C-terminal series ions did not appear. This novel character might be useful for peptide sequence analysis. In addition, dialkyloxyphosphinyl group can be examined by 31P-NMR for peptide conformational analysis and inspection for the degree of racemization during the coupling reaction. PMID- 1917303 TI - Preparations, solution conformation and molecular structures of N,N'-ethylene bridged dipeptides and their derivatives. AB - The solution conformations of novel dipeptides, methyl (2S, 3'S)-3-methyl-2-(2' oxo-3'-isopropyl-1'-piperazinyl)-butanoate (EVV-OCH3), methyl (2S, 3'S)-3-phenyl 2-(2'-oxo-3'-benzyl-1'-piperazinyl) propionate (EFF-OCH3), and their derivatives (Boc-Gly-EVV-OH, Boc-Gly-EVV-Gly-OH, and Boc-Gly-EFF-OH), were studied by 1H NMR measurements and molecular mechanics calculations (1). The molecular structures of Boc-Gly-EVV-OH, Boc-Gly-EFF-OH, and the hydrochloride of EVV-OCH3 were determined by X-ray analyses. The conformations of the piperazinone rings and the side chains of these oligopeptides were clarified. PMID- 1917302 TI - Determination of the disulfide bond pairings in bovine transforming growth factor alpha. AB - A rapid method for determining the three disulfide bond pairings in bovine transforming growth factor-alpha (bTGF-alpha) was developed by digesting bTGF alpha with thermolysin followed by separation of the generated peptides by reversed-phase HPLC. The disulfide-bonded peptides were identified by amino acid sequencing and fast atom bombardment mass spectrometry. The disulfide bond pairings in bTGF-alpha were determined to be homologous to those in the human and mouse TGF-alpha molecules. A species of low bioactivity isolated from the folding/oxidation mixture of chemically synthesized bTGF-alpha was demonstrated to contain two incorrect disulfide bonds. These results indicate that mispairing of disulfide bonds in bTGF-alpha significantly reduces the activity of this molecule. PMID- 1917304 TI - Synthesis of S-alkyl and C-terminal analogs of the Saccharomyces cerevisiae a factor. Influence of temperature on the stability of Fmoc and OFm groups toward HF. AB - The a-mating factor of Saccharomyces cerevisiae Tyr-Ile-Ile-Lys-Gly-Val-Phe-Trp Asp-Pro-Ala-Cys(farnesyl)OCH3, and 10 analogs modified at the cysteine side chain and/or the terminal carboxyl were synthesized using a combination of solid phase and solution phase methodologies. The strategy of synthesis involved the condensation of an amine terminal protected decapeptide with a carboxyl terminal S-alkylated dipeptide ester or amide using benzotriazol-l-yloxy-tris(methylamino) phosphonium hexafluorophosphate as the coupling agent. The protected decapeptide was assembled on a PAM-resin using 9-fluorenylmethoxycarbonyl (Fmoc) for the protection of the Tyr alpha-amine and Lys epsilon-amine and 9-fluorenylmethyl ester (OFm) for the protection of the Asp beta-carboxyl. Premature loss of the OFm group from the HF cleavage was observed at 0-2 degrees, whereas no loss occurred when the cleavage reaction was conducted at -5 degrees. In contrast to these results, the OFm group in Asp(OFm) was partially removed by HF at -5 degrees and was completely stable to HF only at -20 degrees. The S-alkylated dipeptide esters were prepared, in yields from 64% to 88%, via thioalkylation of amine protected or unprotected dipeptide esters using potassium fluoride dihydrate as the base. The use of a tertiary amine as the base of thiohexadecanylation resulted in low reactivity. PMID- 1917305 TI - General method for rapid synthesis of multicomponent peptide mixtures. AB - A method is suggested for the synthesis of multicomponent peptide mixtures. The method is a solid phase synthesis modified in order to give a closely equimolar mixture of peptides with predetermined sequences. The main point of modification is that before every coupling cycle the resin is divided into equal parts and each portion is coupled with a different amino acid. Then the portion are mixed and before the next coupling cycle the resin is again distributed into equal portions. The method is illustrated by the synthesis of a mixture of 27 tetrapeptides and that of 180 pentapeptides. PMID- 1917306 TI - Hydrolysis of beta-casein by gastric proteases. I. Comparison of proteolytic action of bovine chymosin and pepsin A. AB - Hydrolysis of beta A2-casein by bovine chymosin and pepsin A was performed in order to compare the hydrolysis of the two enzymes on this protein. Different conditions have been tested: pH 5.5 for 116h and pH 3.5 for 7 h [E/S = 1/100 (w/w)] for chymosin. pH 3.0 for 24 h [E/S = 1/1000 (w/w)] for pepsin A. Under these conditions 17 peptides were obtained after the action of chymosin and 23 after the action of pepsin A. They corresponded respectively to the cleavage of 14 and 15 peptide bonds for chymosin and pepsin A. However, six of the peptide bonds were only hydrolyzed by chymosin and seven other bonds only by pepsin A. Our results showed a preferential splitting at the Leu-X, Ser-X, and Trp-X bonds for chymosin and Leu-X, Met-X, and Thr-X, for pepsin A. Some of the identified peptides contained sequences with possible physiological roles. PMID- 1917307 TI - Cyclization studies with tetra- and pentapeptide sequences corresponding to beta casomorphins. AB - The tetrapeptide Boc-D-Orn-Phe-D-Pro-Gly-OH and the pentapeptide sequence Boc Tyr(tBu)-D-Orn-Phe-D-Pro-Gly-OH were used to study the influence of different coupling reagents on the yield and purity of these model peptides. The simple structure prevented racemization and cyclodimerization and facilitated the ring formation. The most favorable effects on yield and purity were obtained in both reactions using diphenyl-phosphoryl azide (DPPA) and norborn-5-ene-2,3 dicarboximidodiphenylphosphate (NDPP), while the cyclizations with the powerful activating reagents benzotriazol-1-yl-oxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP) and 2-(1-H-benzotriazol-1-yl)-1,1,3,3 tetramethyluronium hexafluorophosphate (HBTU) with the exception of the cyclopentapeptide reaction with HBTU/4-dimethylaminopyridine gave unsatisfactory results. PMID- 1917308 TI - Infrared spectroscopic discrimination between alpha- and 3(10)-helices in globular proteins. Reexamination of Amide I infrared bands of alpha-lactalbumin and their assignment to secondary structures. AB - We have undertaken a new and more detailed Fourier-transform infrared (FTIR) spectroscopic study of alpha-lactalbumin (in D2O solution) aimed at correlating its secondary structures to observed Amide I' infrared bands. The spectra reported here were interpreted in light of the recently determined crystal structure of alpha-lactalbumin and by comparison with the spectra and structure of the homologous protein lysozyme. Of particular importance is the new evidence supporting the assignment of the band at 1639 cm-1 to 3(10)-helices. This assignment is in excellent agreement with one based on theoretical and experimental studies of 3(10)-helical polypeptides. The frequency observed for 3(10)-helices is distinctly different from that at which alpha-helices are typically found (viz., around 1655 cm-1). In the present study, two bands are clearly resolved in the latter region at 1651 and 1659 cm-1. Both are apparently associated with alpha-helices. These results suggest that for D2O solutions of globular proteins. FTIR spectroscopy can be a facile method for detecting the presence of these two different types of helical conformation and distinguishing between them. This provides a distinct advantage over ultraviolet circular dichroism spectroscopy (UV-CD). This work also provides a basis for future studies of alpha-lactalbumin which examine the effects of environment (e.g., pH, temperature) and ligands (e.g., Ca2+, Mn2+) on its conformation. PMID- 1917309 TI - 2-Chlorotrityl chloride resin. Studies on anchoring of Fmoc-amino acids and peptide cleavage. AB - The esterification of 2-chlorotrityl chloride resin with Fmoc-amino acids in the presence of DIEA is studied under various conditions. High esterification yields are obtained using 0.6 equiv. Fmoc-amino acid/mmol resin in DCM or DCE, in 25 min, at room temperature. The reaction proceeds without by product formation even in the case of Fmoc-Asn and Fmoc-Gln. The quantitative and easy cleavage of amino acids and peptides from 2-chlorotrityl resin, by using AcOH/TFE/DCM mixtures, is accomplished within 15-60 min at room temperature, while t-butyl type protecting groups remain unaffected. Under these exceptionally mild conditions 2 chlorotrityl cations generated during the cleavage of amino acids and peptides from resin do not attack the nucleophilic side chains of Trp, Met, and Tyr. PMID- 1917310 TI - Peptides from chiral C alpha,alpha-disubstituted glycines. Crystallographic characterization of conformation of C alpha-methyl, C alpha-isopropylglycine [(alpha Me)Val] in simple derivatives and model peptides. AB - The molecular and crystal structures of one derivative and three model peptides (to the pentapeptide level) of the chiral C alpha,alpha-disubstituted glycine C alpha-methyl, C alpha-isopropylglycine [(alpha Me)Val] have been determined by X ray diffraction. The derivative is mClAc-L-(alpha Me)Val-OH, and the peptides are Z-L-(alpha Me)Val-(L-Ala)2-OMe monohydrate, Z-Aib-L-(alpha Me)Val-(Aib)2-OtBu, and Ac-(Aib)2-L-(alpha Me)Val-(Aib)2OtBu acetonitrile solvate. The tripeptide adopts a type-I beta-turn conformation stabilized by a 1----4N--H...O = C intramolecular H-bond. The tetra- and pentapeptides are folded in regular right handed 3(10)-helices. All four L-(alpha Me)Val residues prefer phi, psi angles in the right-handed helical region of the conformational map. The results indicate that: (i) the (alpha Me)Val residue is a strong type-I/III beta-turn and helix former, and (ii) the relationship between (alpha Me)Val chirality and helix screw sense is the same as that of C alpha-monosubstituted protein amino-acids. The implications for the use of the (alpha Me)Val residue in designing conformationally constrained analogues of bioactive peptides are briefly discussed. PMID- 1917311 TI - Conformations of neurotensin in solution and in membrane environments studied by 2-D NMR spectroscopy. AB - Two-dimensional HOHAHA and ROESY nuclear magnetic resonance techniques are used to obtain complete proton resonance assignments and to perform a conformational investigation of the neuropeptide neurotensin (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg Arg-Pro-Tyr-Ile-Leu) in aqueous solution, methanol, and membrane-mimetic [deuterated sodium dodecylsulfate (SDS)] environments. Results suggest the absence of discernible elements of secondary structure in water and methanol. ROESY spectra confirm that Lys-Pro and Arg-Pro peptide bonds are all-trans, but that a significant population of cis Arg-Pro bonds arises in aqueous solution, which increases in the environment of SDS micelles. The conformational ensemble of the peptide is observed to narrow as it becomes bound through its cationic mid region to SDS micelles, with the accompanying advent of local extended structure. The overall results indicate the inherent conformational flexibility of neurotensin, and emphasize the environmental dependence of conformation in peptides of medium length. PMID- 1917312 TI - Synthesis and biological evaluation of mouse growth hormone-releasing factor. AB - The recently described mouse growth hormone-releasing factor (mGRF) was synthesized by the solid phase procedure, purified by 2 stages of preparative high performance liquid chromatography and fully characterized. The biologic activity of the 42-amino acid peptide (H-His-Val-Asp-Ala-Ile-Phe- Thr-Thr-Asn-Tyr Arg-Lys-Leu-Leu-Ser-Gln-Leu-Tyr-Ala-Arg-Lys-Val-Ile-Gln-Asp-Ile-Met-Asn- Lys- Gln-Gly-Glu-Arg-Ile- Gln-Glu-Gln-Arg-Ala-Arg-Leu-Ser-OH) was assessed in primary cultures of both mouse and rat anterior pituitary cells and compared to synthetic rat (rGRF) and human (hGRF) growth hormone-releasing factors. mGRF was equipotent to rGRF in mouse somatotrophs but slightly less potent in rat somatotrophs, while hGRF was 3-5 times less potent in both rodent species. PMID- 1917313 TI - Enhancement of solubility by temporary dimethoxybenzyl-substitution of peptide bonds. Towards the synthesis of defined oligomers of alanine and of lysyl glutamyl-glycine. AB - The synthesis of the model compound Aloc-Ala-Ala-Dma-Ala-Ala-OMe has been described as an illustration of the fact that a large group reversibly alkylating the amido group of an oligomer can disturb the regularity of a peptide backbone, oppose its aggregation and thus enhance its solubility greatly, affording synthons for further oligomerization. Application of such a group not only affects the solubility, but alters also the properties of the intermediates. The concomitant change in reactivity may run to such an extent that N-alkylation of oligomers has to be abandoned (this was encountered in the attempted synthesis of Lys-Glu-Dmg). Consequently, the solubility of the growing protected peptide chain will become progressively less and in the mentioned example the oligomerization had to be terminated at the dodecapeptide level, indicating the severe need for reversible "structure-breaking" functions. PMID- 1917315 TI - Dominant exudative vitreoretinopathy: a sporadic case with a normal platelet aggregation study. AB - Case report of a woman with the characteristics of dominant exudative vitreoretinopathy. These anomalies are however unilateral and the family study is not very contributive. A platelet aggregation study carried out on the patient and 3 family members is normal. PMID- 1917314 TI - Submacular scar excision in age-related macular degeneration. AB - Disciform scars secondary to age-related macular degeneration were surgically removed in three patients. Postoperative visual acuity improved minimally in one case and decreased in the other two cases. The results suggest further investigation is needed with possible modifications of our technique for future studies. PMID- 1917316 TI - A traumatic cyst of the sclera. AB - The author describes a traumatic implantation cyst of the sclera which developed about two years after an injury with a knife, which caused a perforating scleral wound. The wound was sutured with the operating microscope. The possible mechanisms of the development of this cyst are discussed. Ophthalmologists should still bear in mind the possibility of the development of cysts of the sclera after injuries, which are rare complication nowadays. PMID- 1917317 TI - Toxicity of high-dose intravitreal dexamethasone. AB - The intravitreal toxicity of a high concentration of dexamethasone was studied in New Zealand white rabbits. No toxicity was observed after intravitreal injections of up to 4.8 mg/0.2 ml. PMID- 1917318 TI - Uncontrolled primary angle closure glaucoma: results of early intercapsular cataract extraction and posterior chamber lens implantation. AB - In this study we retrospectively evaluated the effect of intercapsular or extracapsular cataract extraction and posterior chamber lens implantation in 67 eyes of 57 patients with different types of primary angle closure glaucoma (PACG) in combination with cataract. We subdivided this patient population into three groups, based on the preoperative methods of intraocular pressure (IOP) control. The best results were obtained in patients with acute PACG (55% IOP reduction) and in patients with uncontrolled PACG (44% IOP reduction). In the other PACG groups an IOP reduction of between 20 and 33% was achieved. A long-term postoperative IOP of less than 21 mmHg was established in 63 eyes or 94%. In 91% the glaucoma medication was reduced, 65% of all eyes needed no glaucoma medication postoperatively. We conclude that an intercapsular cataract extraction with PC-IOL implantation should be considered in both controlled and uncontrolled PACG in patients with cataract, instead of filtering surgery or combined procedures. Even in eyes with relatively good visual acuity, cataract extraction might be considered as a means of achieving glaucoma control. PMID- 1917319 TI - Long-term effect of erbium-YAG laser (2.9 microns) on the primate cornea. AB - An erbium-YAG (2.9 microns) laser was used in the primate eye to irradiate the anterior surface of the cornea in one group and the midstroma in another group after temporary lamellar keratectomy. The eyes were observed clinically up to a period of eight months, when the animals were sacrificed. The initial opacification of the cornea caused by the erbium laser application gradually disappeared over the observation period and was replaced by a faint haze. The healing process was faster in Group II (midstromal laser ablation). Some degree of flattening of the cornea after laser ablation was seen in both groups by photokeratoscopy. At the end of the observation period, the irradiated corneas demonstrated normal appearing corneal structure without significant damage to the corneal epithelium, stroma, or endothelial cells. Further experimental studies are needed to improve the laser delivery system and reduce the degree of corneal damage produced by long laser pulses. PMID- 1917321 TI - Improvement of visual acuity and corneal physiology in keratoconus by fitting aspherical, high oxygen-permeable contact lenses. AB - Keratoconus is a condition in which the cornea assumes a complex irregular curvature caused by central corneal thinning. The abnormal topography of the cornea in combination with central corneal scarring results in an impaired visual acuity. Even in mild cases spectacles do not correct vision adequately. The use of hard contact lenses with a spherical geometry in the past has already given a marked therapeutic improvement. The use of these lenses however, is complicated by hypoxia and mechanical trauma of the cornea. These complications could theoretically be avoided by fitting elliptical lenses with a high oxygen transmission. To investigate this hypothesis we compared low oxygen-permeable spherical lenses with high oxygen-permeable elliptical contact lenses in a group of twenty patients with mild keratoconus. Our results showed both a marked subjective and objective visual improvement after fitting elliptical lenses with a low incidence of complications. PMID- 1917320 TI - The effect of isosorbide-mononitrate eye drops on the human intraocular pressure and aqueous humor dynamics. AB - In a randomized, double-masked, single drop study the effect of topical isosorbid mononitrate (ISMO) 0.5% eye drops, the main metabolite of isosorbid-dinitrate, widely used in the treatment of coronary heart diseases, was studied in patients suffering from open angle glaucoma or ocular hypertension. There was no statistically significant IOP change within 8 hours posttreatment after topical administration of ISMO 0.5%. There were no side effects after application of the ophthalmic solution of ISMO 0.5%. There were no significant changes in blood pressure and pulse rate either. A 2% ophthalmic solution of ISMO was investigated with respect to a response on the aqueous humor dynamics in 10 healthy volunteers. Anterior chamber fluorophotometry revealed a mean increase in aqueous flow of 39% within 3 hours after topical application (P less than 0.01). However, in comparison to the placebo treated fellow eyes there were no statistical significant difference in aqueous humor flow during the time of investigation. There was a statistical significant reduction of IOP during the same time period (p less than 0.03) in all treated eyes. PMID- 1917322 TI - Ectopic hematopoiesis in the human iris. AB - Hematopoietic islands of erythroblastic precursor cells with mitotic activity were found pathologically in the distorted iris of a 35-year-old diabetic male. The eye had been enucleated for absolute hemorrhagic glaucoma occurring secondary to central vein occlusion and complicating previous vitrectomy, repair of retinal detachment and extracapsular cataract extraction. PMID- 1917323 TI - Phacoanaphylactic endophthalmitis: a clinicopathologic review. AB - Lens-induced uveitis or phacoanaphylactic endophthalmitis (PE) is a chronic endophthalmitis with a zonal granulomatous inflammation surrounding a ruptured lens. One hundred forty four cases of PE were retrospectively evaluated clinically and histopathologically. The disease was not well recognized clinically as only six of the cases were given the clinical diagnosis of PE. Most cases (80%) occurred after trauma, surgical or non-surgical. The time after injury varied from two days to fifty nine years. Of those individuals less than 55 years of age who had no history of trauma. 29% were noted by clinical history to have microphthalmia. Although classically the inflammation of PE has been described as being confined to the anterior aspect of the eye, the choroid was involved with an inflammatory reaction in 76% of the cases. PMID- 1917324 TI - Abstracts of the 185th meeting of the NOG, Maastricht 20-22 March, 1991. PMID- 1917325 TI - Myofunctional therapy in Germany. PMID- 1917326 TI - An approach to digitsucking cases. Part one. Consideration of methods of instructions for digitsucking cases. PMID- 1917327 TI - [The young and tobacco: can we be optimistic?]. PMID- 1917328 TI - [Consensus methodology in the health sector]. PMID- 1917329 TI - [Perceived health and functional capacity of a non-institutionalized elderly population in Barcelona]. AB - In order to explore the perceived health and functional capacity in the elderly, a cross-sectional study was undertaken in a representative sample of the non institutionalized population aged 65 and over, resident in Barcelona (N = 1,288), and included in the 2nd Health Interview Survey. Sociodemographic information was collected, as well as perceived morbidity, sensorial problems and functional capacity (measured by the activities of daily living [ADL]). Some 60.3% of the elderly reported having "good" or "very good" health, and 56% reported being able to do all ADL without difficulties. Women in general reported a worse perceived health and a higher chronic limitation in each age group (p = 0.001). Age was not significantly associated with perceived health, but was...associated with disability (ADL) (p = 0.001). Variables with a stronger association with "poor", "bad" o "very bad" perceived health were: comorbidity (OR = 3.69 IC 95% = 2.60 5.25), restricted activity (OR = 3.25 IC 95% = 1.86-5.66) and incapacity in any of the basic ADL (OR = 2.15 IC 95% = 1.38-3.36). The elderly who were dependent in any of the basic ADL were more frequently female, 75 or more years old, and in 10.5% of the cases did not receive any personal help. The present study gives a general description of the health status and functional capacity of the elderly and identifies a group of old people with unmet basic care needs. PMID- 1917331 TI - [Level of knowledge of patients with type II diabetes mellitus in primary care]. AB - A personal interview to 148 patients was carried out with the aim of getting to know the level of information of type II diabetic patients at an Urban Health Center in Santander. A validated questionnaire made up of 14 questions on general aspects of diabetis, dietetic habits and capability to handle complications was used. The Cronbach's alpha coefficient of questionnaire was 0.69. The correct answer average was 6.3 (IC = 5.9-6.5). Patients were best informed about general aspects and had much less information with regard to the handling of complications and to their diet. The differences among these three sections of questions were significative (p less than 0.001). The patients under diet treatment obtained worse results than those treated with oral hipoglucemiants and insulin. Our results are worse than those reported by other similar populations at a national level. Also, and due to the differences in knowledge within this group, we believe that the establishment of groups and subgroups when educating diabetic patients is possible and also highly recommended. PMID- 1917330 TI - [Tobacco use in the province of La Garrotxa. Comparative study 1982-1986]. AB - The objective of this study is to compare the prevalence of smoking among young students of the area of La Garrotxa between 1982 and 1986. Two surveys were made, following the same methodology, interviewing two samples of student population 13 to 25 years old. The total number of interviewed students were 1,039 in 1982 and 1,133 in 1986. The smoking prevalence was lower in 1986 than in 1982, decreasing from 55% to 35%. This difference was due to a decrease in the prevalence of those younger than 17 in both sexes and remained stable after adjusting for age, sex and school. The initial age for experimental smoking was delayed by 1 year from 1982 to 1986. The proportion of smoker parents was not different between both periods. We conclude that smoking habit has decreased in younger people, and this is probably due to a delay in the age of smoking initiation. PMID- 1917332 TI - [Opinion on health priorities in the community of Valencia]. AB - In this study we have used a qualitative approach partially based on the Delphi technique to establish the ten priorities for health in the Valencian Community for the next five years. Two rounds of mail surveys were made sending questionnaires to 1834 people including Health Councillors of the Town Halls, nurses and doctors of the three valencian provinces. The overall response rate was 28.3%. The priorities which were perceived as most important by the respondents were the development of primary care, improvements in the management of health services and the development of preventive medicine. The fourth and fifth places of the ranking were: improvements of emergency services and increasing the budget devoted to hospital care. The 6th priority was preventive measures in cardiovascular diseases, the 7th actions against drug abuse, the 8th special attention to childhood and ageing populations and the last two priorities were protection of the environment and infectious diseases prevention. We consider this approach as useful to obtain additional valuable information complementary to the information obtained from traditional statistics or health surveys specially in the areas of management, diseases prevention and actions towards special groups of population. PMID- 1917333 TI - [About avoidable mortality]. PMID- 1917334 TI - Is attachment of bacteria to the epithelial cells of the nasopharynx the key to otitis media? AB - Epithelial cells from the nasopharynx of 42 young healthy individuals were obtained by swabbing. The filtered cellular mixture was stained with acridine orange and bacteria attached to the epithelial cells were counted using a fluorescence microscope. Simultaneously qualitative and quantitative bacteriological analyses were performed. Young individuals (less than 2 years) had significantly more attached bacteria than older ones (11-15 years) (P = 0.0001). The presence of middle ear pathogens in the nasopharynx of young children was significantly more prominent than in the older age groups (P less than 0.001). Attachment of middle ear pathogens to nasopharyngeal epithelial cells of young individuals may predispose to otitis media. PMID- 1917335 TI - Volunteer otolaryngology practice in rural Mexico. AB - Medical missions, particularly with religious or military affiliation, are becoming more commonly performed in the Third World. Modern surgical techniques for correcting congenital anomalies frequently require staged operative procedures with long-term follow-up. However, in remote or isolated Third World villages, operative procedures must often be done at a single setting, without staging, utilizing limited intraoperative equipment. Very short postoperative hospitalizations may be all that are available and follow-ups are severely limited. We report our experience on a two-week mission to Mexico where 46 major otolaryngologic surgeries were performed. Follow-up was limited, in most patients, to visits within only a few days of the surgical procedure. Techniques for Third World otolaryngologic surgical experience are discussed including the correction of cleft deformities. PMID- 1917336 TI - Management of airway obstruction in the Pierre Robin sequence. AB - A 10-year retrospective study of the management of airway obstruction in 26 infants with Pierre Robin sequence was made. It was not possible when the infant was first seen to assess the future severity of the airway obstruction but later 3 distinct groups could be identified according to the airway management which had become necessary. The deaths from respiratory obstruction indicate the prime importance of airway management. Laryngoscopy for intubation or endoscopic evaluation was often difficult and sometimes could not be achieved. 'Awake intubation' without general anesthesia has proved to be safer and less difficult using a special purpose slotted laryngoscope. Airway management should be individualized following the progressive sequence of posturing in the prone position, nasopharyngeal tube, endotracheal intubation and tracheotomy until successful control is achieved as indicated by the clinical features and pulse oximetry. PMID- 1917337 TI - Pregnancy-induced hypertension and congenital hearing loss. AB - It has been suggested that pregnancy-induced hypertension (PIH--pre-eclampsia or toxaemia of pregnancy) may cause sensorineural hearing loss (SNHL) in the offspring. To establish the validity of this concept a clinical survey of the prevalence of congenital hearing loss in relation to PIH in the South East Kent Health District in the United Kingdom over a period of 4 years was undertaken. Description of the temporal bones in a case of PIH is presented. The total number of live births in this period was 12,927, out of which 512 mothers (3.9%) were diagnosed as having PIH. To date 17 cases of bilateral SNHL have been diagnosed in this period (excluding known syndromes, conductive hearing loss and unilateral SNHL). One of the mothers of these children had PIH. It is possible that otologists, in the absence of any obvious cause, have attributed the cause of bilateral SNHL to PIH. Histopathological findings in temporal bones from a 29 week fetus, whose cause of death was severe maternal hypertension, showed massive haemorrhages in the inner ear and middle ear and internal auditory meatus, a frequent finding in temporal bones obtained at autopsy from fetuses and neonates who were born prematurely. This study suggests that PIH per se is unlikely to cause SNHL in the newborn. PMID- 1917338 TI - The Jervell and Lange-Nielsen syndrome. AB - Deafness and electrocardiographic changes (prolongation of the Q-T interval and inversion of the T wave) with a clinical picture of syncopal attacks and sudden death, were described as a distinct syndrome by Jervell and Lange-Nielsen in 1957. The syndrome is inherited as an autosomal recessive trait. In this study, all the cases reported since 1957 and their proposed prevalence are reviewed. The authors describe the 4 cases they have studied, all of which presented congenital sensorineural hearing loss and electrocardiographic changes characteristic of the syndrome. The relatively high number of cases they have encountered casts doubt on literature that states that the syndrome occurs more frequently in Northern European populations. Consequently, it is advisable to perform an electrocardiogram in all children affected by congenital deafness. PMID- 1917339 TI - The impact of a syndromal diagnosis on surgery for congenital minor ear anomalies. AB - Between 1964 and 1986, 104 ears of 86 patients with a minor congenital ear anomaly underwent an exploratory tympanotomy at the Institute of Otorhinolaryngology of the University Hospital Nijmegen. A classification of these anomalies is proposed based on the surgical findings and results. The 4 groups in this classification are: isolated stapes ankylosis, stapes ankylosis associated with an anomaly of the malleus and incus, an isolated anomaly of the malleus and incus with a mobile stapes footplate and finally, aplasia of the oval and/or round window. In a total of 29 ears (22 patients) out of these 104 ears, the anomaly formed part of a syndrome. The various syndromes and the anomalies encountered are discussed. The impact of a syndromal diagnosis on the outcome of reconstructive ear surgery is discussed per syndrome. PMID- 1917340 TI - Hearing loss and ear disorders in Malaysian school children. AB - In Malaysia 1,307 randomly selected primary school children were screened to find out the prevalence of hearing loss and middle ear disorders. Seventy-six students (5.81%) failed the screening audiometric test. There were 95 students (7.26%) with middle ear disorders. History of ear discharge was absent in 24 out of 57 cases with CSOM (42.11%) (P less than 0.001). Forty-three out of 95 children having middle ear disorders passed the screening audiometric test (P less than 0.01 Fisher exact test). Screening audiometric test fails to detect about 46% of cases with middle ear disorders. Screening audiometric test and otological examination if conducted by the school health medical officers regularly will be able to detect almost all the cases with hearing loss and middle ear disorders. PMID- 1917341 TI - Long-term follow-up of chronic maxillary sinusitis in children. AB - In 26 children, aged between 3 and 7 years, the course of therapy-resistant chronic maxillary sinusitis over a mean period of 6 years and 3 months, was analysed. The results showed that spontaneous cure had occurred in 24 of the 26 children, on average after they reached the age of 7 years. The chronic character of upper respiratory tract infections in young children is difficult to explain. PMID- 1917342 TI - The open surgical approach to subglottic hemangioma. AB - The management of subglottic hemangioma in infants remains controversial. We report two patients in whom an open surgical approach was utilized to completely excise the subglottic hemangioma. Both children have been successfully extubated and have remained symptom-free since that time. PMID- 1917344 TI - Airway obstruction in Hurler's syndrome--radiographic features. AB - The mucopolysaccharidosis (MPS) diseases are progressive clinical disorders which are characterized by a deficiency of lysosomal enzymes. In MPS I (Hurler's syndrome), reduced activity of alpha-L-iduronidase leads to intralysosomal storage of dermatan and heparan sulfate in various tissues. Airway obstruction is a frequent problem in these patients, often secondary to abnormal cervical vertebra, a short neck, a high epiglottis, and mucopolysaccharide infiltration of the soft tissues in the upper aerodigestive tract. Evaluation of these abnormalities may include plain film and videofluoroscopic examinations of the airway. The therapeutic and diagnostic implications of such studies are discussed in a review of 4 patients with Hurler's syndrome manifesting upper airway obstruction. PMID- 1917343 TI - Otogenic brain abscess in childhood. AB - Brain abscesses are quite rare complications of middle ear infections. Although temporal lobe abscesses are more common than cerebellar abscesses, the converse was found to be true in our series of 10 cases. Eight cases of cerebellar abscess and 2 cases of temporal lobe abscess in the paediatric age group were reported including 4 cases of latent brain abscesses which manifested themselves after mastoidectomy for middle ear infection. Brain abscess is by far the most serious of otogenic complications. PMID- 1917345 TI - Nutritional status of vitamin A in a healthy elderly population in Japan. AB - In this study nutritional status of vitamin A (VA) in a healthy elderly population in Japan was examined. Healthy elderly volunteers with mean age of about 67 at the start of the study were recruited. Analysis of serum VA concentration was carried out four times in two consecutive years. No deficient subject was detected from the serum VA concentration. Only small percentages were assessed to be in a low or marginal VA status. Consequently, the nutritional status of VA in the elderly Japanese seemed to be adequate judging from the serum VA concentration. Contrary to that, mean values of daily dietary intake of VA in both females and males were almost acceptable but the respective values varied over a wide range with no correlation with the serum VA concentrations. Accordingly, serum VA concentration provided a more definitive evaluation to assess VA nutriture than its dietary intake. PMID- 1917346 TI - Vitamin A in the urine of carnivores. AB - Vitamin A levels (retinol equivalents) in the urine of canines were between 423 ng/ml (dog) and 6304 ng/ml (silver fox). Neither vitamin A nor vitamin E was found in the urine of herbivores, omnivorous and rodents. No vitamin A but low levels of vitamin E were detected in cats. Vitamin A in the urine was present as retinol and retinyl esters (basically retinyl palmitate/oleate). The total excretion of vitamin A represented 15 to 63% of the daily uptake in dogs, while less than 4% of vitamin E was excreted. Results after precipitation and ultracentrifugation indicate that similar carrier proteins may exist for retinol, retinyl esters and alpha-tocopherol in the urine. The biological significance of this phenomenon is discussed with regard to the high concentrations of retinyl esters in the blood plasma of carnivores bound to lipoproteins. PMID- 1917347 TI - Comparison of plasma alpha- and gamma-tocopherols after oral and intramuscular administration of RRR-alpha-tocopherol or RRR-gamma-tocopherol to weanling pigs. AB - Equimolar amounts of either RRR-alpha-tocopherol (alpha-TOH) or RRR-gamma tocopherol (gamma-TOH) were given as single doses orally and, as water-based emulsions, by intramuscular (i.m.) injection to weanling pigs. Venous blood was sampled at regular intervals and plasma was analyzed for comparison of alpha-TOH and gamma-TOH kinetics. Irrespective of the method of application no significant differences were found between alpha-TOH and gamma-TOH in (a) the maximum increase above initial concentration (delta C), (b) the time of peak concentration (tmax), and (c) the time from half-maximum concentrations on the ascending and the descending parts of the plasma curve. However, alpha-TOH was retained longer in plasma than gamma-TOH, and the areas-under-curve from Oh to 24 h and from Oh to 48 h (AUC0-24 and AUC0-48) were significantly greater for alpha TOH. In diarrheic pigs given oral gamma-TOH, tmax was prolonged, delta C was lower and AUC0-24 and AUC0-48 were reduced compared with healthy pigs (p less than 0.05). The results indicate that pigs absorb both vitamers to a similar extent but that gamma-TOH is eliminated from plasma more rapidly. PMID- 1917348 TI - Riboflavin status in a group of institutionalized elderly. AB - We studied the riboflavin intake and biochemical status in a representative sample (20 males and 52 females) of institutionalized elderly people (aged 68-95) living in the Autonomic Community of Madrid. The riboflavin density of the diet was in general higher than the recommended amount, so the quality of the diet, related to riboflavin, can be considered satisfactory, and probably the caloric deficit is the major cause of the low intakes found. We found no correlation between the intake and biochemical status of riboflavin. The elderly with erythrocyte glutathione reductase greater than 1.2 are not those who have lower intakes. The cause of the deficit could be the different malabsorption problems and diseases that affect people as age increases. PMID- 1917349 TI - Bioavailability of folate following ingestion of cholestyramine in the rat. AB - The effect of cholestyramine ingestion on the intestinal deconjugation and absorption of folic acid (PGA) and brewers yeast folate was investigated using a rat bioassay and liver folate uptake as the response parameter. Male weanling Sprague Dawley rats were depleted on a low AIN-76A formulated basal diet for 21 days. During a 14 day repletion period folic acid (PGA) and brewers yeast were added to provide 0.25, 0.5 and 1.0 mg of folate per kg of diet. Cholestyramine was administered directly as part of the diet at 1.1%. All diets were made isonitrogenous and isocaloric. Based on a parallel line assay, the relative biological value of folate for PGA + cholestyramine (79) was significantly different from the standard diet (PGA = 100), while those for brewers yeast (88) and for brewers yeast + cholestyramine (88) did not differ from the standard diet. Ingestion of cholestyramine significantly reduced the bioavailability of PGA versus brewers yeast folate in rats. PMID- 1917350 TI - An investigation into the effect of different intakes of vitamin C on drug metabolism in Gambian men. AB - Hepatic mixed-function oxidase activity was measured in Gambian men during a period of low seasonal vitamin C intake and after vitamin C supplementation. Demethylation of methoxyphenylacetamide (methacetin) was followed using a breath test, in which the exhalation of 13C-enriched CO2 was measured following an oral dose of 13C-methacetin. Vitamin C supplementation, sufficient to increase plasma levels significantly, did not influence methacetin metabolism. However, methacetin metabolism in unsupplemented men appeared normal in the majority of cases. Hepatic tissue may not have been sufficiently depleted of vitamin C to impair the activity of the mixed function oxidase system. PMID- 1917351 TI - The effect of vitamin E (alpha-tocopherol) supplementation on hepatic levels of vitamin A and E in ethanol and cod liver oil fed rats. AB - Eight groups of 5 rats were fed 8 differing liquid diets with and without ethanol, cod liver oil and/or increased levels of vitamin E. Hepatic levels of vitamins A and E were determined following the 28-day feeding time. Ethanol consumption decreased the levels of hepatic vitamin E (p less than 0.05), vitamin A (p less than 0.05) and the ratio of vitamin A/E (p less than 0.05). Hepatic levels of vitamins A and E were unaffected in rats fed cod liver oil. Supplementation of the normal dietary level of 30 IU of vitamin E per kg diet, with an additional 142 IU alpha tocopherol/kg diet, restored hepatic concentrations of vitamin E to normal levels in alcohol-fed rats. The hepatic levels of vitamin A in rats fed ethanol diets supplemented with vitamin E were less than that of control rats but were 4.3 times greater than that of rats on ethanol diets unsupplemented with vitamin E. However, the vitamin A and E ratio was equal to normal in this group of rats. The vitamin A/E ratio was reduced in liver of rats fed non-alcoholic diets supplemented with vitamin E due to increased levels of hepatic vitamin E. Additionally, rats fed cod liver oil diets containing ethanol also indicated decreased hepatic vitamin A and E levels. However, these levels were greater than that of rats fed only alcoholic diets suggesting that these vitamins are replaced by the vitamin A and E content in the cod liver oil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917352 TI - Biosynthesis of ascorbic acid and riboflavin in radiated germinating chickpea. AB - Biosynthesis of ascorbic acid and riboflavin in radiated germinating chickpea seeds was studied at ambient room temperature (20-35 degrees C). Synthesis of these vitamins increased significantly with increasing germination time up to 120 hrs depending upon the treatment (P less than 0.05). Maximum amounts of ascorbic acid, 22.32 and 16.84 mg/100 g (wet weight) were found in the 0.10 kGy samples after 120 hrs of germination in tap and distilled waters respectively. Radiation dose of 0.20 kGy resulted in the development of maximum riboflavin, 11.4 and 11.0 micrograms/g (dry weight) on germination in tap and distilled waters respectively. An overall significant linear relation (r = 0.954 to 0.957) was found between vitamin biosynthesis and germination time up to 120 hrs in both the radiated and unradiated chickpea. PMID- 1917353 TI - Protective role of ascorbic acid and vitamin B-complex against pesticide-induced clastogeny in bone marrow cells of mice. AB - Concurrent administration for one week of vitamins B-Complex (0.3 ml of 1% Polybion) or ascorbic acid (0.25 ml of 1% Redoxon, to 8-week old albino swiss mice, Mus musculus along with organophosphorous pesticide Malathion or carbamate pesticide Rogor (both 1 microliters/kg b.wt.) could significantly decrease the chromosome-clastogeny rate induced by the pesticides alone in the metaphase chromosomes of bonemarrow cells. The vitamins were not clastogenic, whereas the Malathion proved to be clastogenic four-times and Rogor six-times more than the control rate. The vitamins seem to reduce the incidence of fragmentation and subsequent rearrangements induced by the pesticides. On the basis of the available literature, it is presumed that the vitamins might be preventing the formation of mutagenic lipid conjugates of biometabolised forms of the pesticides. PMID- 1917354 TI - The interrelation of urinary calcium and sodium intake in healthy elderly Japanese. AB - To evaluate whether habitual excess sodium intake is significant as a risk factor for calcium loss in elderly Japanese, a relationship between calcium excretion and sodium excretion was studied in 39 male and 44 female Japanese, aged 60 and over. They are healthy, free-living and consuming a self-selected diet. A significant positive correlation between urinary calcium excretion and sodium excretion per 24-hour was observed both in males (r = .415, p less than 0.01) and in females (r = .330, p less than 0.05). The relationship was still significant even after adjustment for sex, age, body mass index, alkaline phosphatase levels and protein as well as calcium and phosphorus intake. It was estimated that the increase in urinary calcium excretion was about 1.0 mmol/day per 100 mmol increase in urinary sodium excretion. PMID- 1917355 TI - Selection of carbohydrate to protein ratio and correlations with weight gain and body fat in rats allowed three dietary choices. AB - In order to determine the spontaneous macronutrient choice of a normal rat population, we allowed growing animals to choose their food among three isocaloric diets: 5% protein - 40% carbohydrate; 45% protein - 40% carbohydrate and 5% protein - 70% carbohydrate, and we measured macronutrient intake, carbohydrate to protein (C/P) ratio and weight gain twice weekly during 9 weeks. At the end of the study, final body weight gain and fat accretion as well as brain serotonin content were measured. Protein consumption increased and fat intake decreased steadily during the assay (from 18.8 to 29 kcal% vs. 35.7 to 25.2 kcal%) whereas carbohydrate consumption remained constant (approx. 46 kcal%) ("carbohydrate homeostasis"), and as a consequence the C/P ratio dropped. There were great variations in total protein consumption between animals (13-32 kcal%) and an inverse relationship with fat intake because carbohydrate consumption was constant. Daily weight gain was negatively correlated with the corresponding C/P ratio, as were final weight gain and body fat content with the global C/P ratio characterizing the food choice of each rat. The concentrations of brain serotonin and 5-hydroxyindole acetic acid were rather uniform and did not show any correlations with any of the other variables. The percent food protein chosen by the animal determined the outcome of the trial at 9 weeks, i.e. food intake, weight gain and body fat accretion. In this experimental model, body fat accumulation is, therefore, directly linked to the protein content of the diet, inversely proportional to the fat level and not related to the carbohydrate content. Since the animals increase the proportion of protein in their food with age above basic nutritional requirements, it is postulated that the macronutrient choice of the rat is also determined by the need of the brain for a proper and balanced supply of neurotransmitter precursors adapted to the situation of each animal. PMID- 1917356 TI - Protein-chemical standardization of the erythrocyte glutathione reductase activation test (EGRAC test). Application to hypothyroidism. AB - The erythrocyte glutathione reductase activation coefficient (EGRAC) is an index of riboflavin deficiency or, more exactly, of FAD deficiency in man. In this report a sensitive version of the EGRAC test is introduced that is based on the molecular properties of glutathione reductase and its FAD-free apoenzyme. The hemoglobin concentration of the blood sample can be estimated simultaneously using the spectrophotometric absorption at 340 nm. - The method was tested for 33 thyroidectomized patients in comparison with a euthyroid control group. From the average EGRAC values (1.40 vs. 1.22) it was deduced that the average free FAD level was approximately 2 times lower for the patients' than for the control group. Discussed is the role of the EGRAC test in hormonal and nutritional disorders. PMID- 1917357 TI - Urinary vitamin excretion after lactation: a test for hydrosoluble vitamin requirement during lactation in the rat. PMID- 1917358 TI - Grim prospects for AIDS/HIV spread worldwide. PMID- 1917360 TI - WHO sets guidelines for preventing HBV/HIV transmission in healthcare settings. PMID- 1917359 TI - 10 million AIDS orphans forecast by year 2000. PMID- 1917361 TI - Cities in distress: a rescue strategy. AB - Too serious to ignore any longer, the world's rampant urban health deterioration now requires serious and fast rescue efforts by not only the health authorities but all government and community sectors. One impetus to national plans of action was the technical discussions at this year's Forty-fourth World Health Assembly whose goal was to map out "strategies for Health for All in the face of rapid urbanization." It became evident that primary health care should be made as relevant to the inmates of the cities' shantytowns as it is to rural inhabitants. ICN's statement at the discussions (p. 108) shares WHO's preoccupation with the unacceptable urban environmental health standards and recommends a strategy based on a primary healthcare approach and intersectoral cooperation. During the talks ICN nurse consultants also voiced ICN's views on mobilizing the communities and the necessary involvement and education of women, who are considered the best representatives from among the urban poor to be involved in community health. Nurses are an indispensable part of these urban health teams and, if they are not already, should start now to become involved in urban policymaking and planning and consider how their national nurses' association can individually or collaboratively support healthy city projects and national healthy city networks. Some guidelines for future strategy can be derived from the following overview of the magnitude of the urban crisis and the WHA technical discussions. PMID- 1917362 TI - Challenging healthcare economics and technology to save the environment. AB - Nurses as frontline healthcare personnel can become strong advocates for a healthy environment, and the place to start is in the healthcare setting itself. The growing environmental awareness behooves nurses to address many professional practices that harm the environment. Below, how nurses in South Australia are questioning a hospital's practices and choice of technology. PMID- 1917363 TI - The status of nursing administrators in Hungary. AB - The College for Health Workers was established in 1973 in Hungary with the aim to educate and train highly qualified healthcare workers to meet all the demands of special health care. Although matrons (nursing administrators) who have graduated from the College are capable of performing special tasks to ensure quality care, they do not have the corresponding authority and recognition. Below, how nurse researchers in Hungary proved this hypothesis. PMID- 1917364 TI - Strategies for managing conflict. AB - As nursing becomes more international, it is becoming increasingly important to know how different cultures respond to various phenomena. Below the authors compare conflict handling modes of Italian nurses with those of American nurse and business managers. PMID- 1917365 TI - Even her feminist friends see her as "only" a nurse. PMID- 1917366 TI - Single-use syringes herald drop in hepatitis B/HIV risk. PMID- 1917367 TI - Paris Declaration on women, children and AIDS. PMID- 1917368 TI - Knowledge and attitude concerning mental health of primary health care workers in Nigeria. AB - Primary health care (PHC) in developing countries continues to rely heavily on paramedical personnel. Using a structured questionnaire, 207 PHC workers in Nigeria were assessed on the concept, attitude to, detection and treatment of mental disorders. PHC workers without previous exposure to mental health training were significantly more likely to hold on to traditional views on the aetiology of mental disorders. Most of the health workers (82%) indicated that mental disorders accounted for 5% or less of their patient load. Detection rate for the vignette on neurosis as a case of mental disorder was poorer than that for psychosis (36% vs. 71% of respondents respectively). Psychopharmacological knowledge of the PHC workers was found to be poorest for antidepressant medication. Only 30% of the health workers could suggest specific types of mental health programme that could be introduced at PHC level. Many of them (72%) expressed a generally negative attitude towards mentally ill patients. Suggestions are made on the short and long term training requirements of the PHC workers in order to ensure the successful integration of mental health care into the primary health care programme in Nigeria. PMID- 1917369 TI - The use of inpatient psychiatric care by immigrants in a London Borough. AB - The prevalence of admission to psychiatric inpatient care in the major immigrant groups in the London Borough of Newham in 1982 is surveyed and results discussed with reference to relevant published literature. High admission rates were found among young West Indian men and older West Indian women, Pakistani men, older Indian women, Irish women and women from the West African new commonwealth. Women from the East African new commonwealth had a low admission rate. The diagnostic mixture found in patients from the various groups is discussed. PMID- 1917370 TI - A survey of patients' attitudes towards inpatient psychiatric ward rounds. AB - Attitudes towards the multidisciplinary ward round were assessed in fifty psychiatric inpatients, from two wards, using a semi-structured interview. About three quarters of them had at least a moderately favourable impression of the ward round but more than half would still prefer not to be interviewed in this way. Levels of anxiety and perceived helpfulness were positively correlated. Afro Caribbeans found the interview significantly less helpful, less understandable and less memorable. Men found it less helpful than women and there were differences found between the two wards. Possible explanations for these findings are discussed. PMID- 1917371 TI - Suicide by burning in Korea. AB - Of 2,143 admissions following suicide attempts over a seven year period (1980 1986) in Seoul, Korea, there were 38 cases (1.8%) of suicide by burning. These cases were matched by age and sex with a control group of suicide attempts in general and were investigated for psychosocial differences from other suicide attempters. No significant differences were found in social factors such as education, religion, marital status, seasonal change and occupation. The majority of suicide attempts by burning were in a public place (73.7%) and were eventually fatal despite intensive medical treatment (78.9%). Half (52.7%) suffered from significant mental disorders and marital disharmony. PMID- 1917372 TI - The Red Lion Lounge Bar: an unusual setting for day care of the elderly mentally infirm. PMID- 1917373 TI - Addressing racism in psychiatry: is the therapeutic community model applicable? AB - Several reports have documented the failure of statutory psychiatric services in Britain to provide for the needs of clients from minority ethnic groups. Black clients are particularly underrepresented in Psychotherapy for reasons which are complex and varied, but include the institutionalised racism which pervades British society. We argue that the Therapeutic Community (TC) model of treatment (or aspects of it deployed in other mental health situations) provides a potential for a less racist service. Using the Henderson Hospital TC as a case in point, we argue that the TC is an approach which can meet the needs of black peoples. However, it is acknowledged that despite the ideological suitability of the TC model for black clients, in practice the Henderson Hospital is not fulfilling its role in providing therapy to this group. We discuss possible explanations and suggest the practical changes necessary, so that Henderson Hospital can meet the needs of clients in a multi-cultural Britain. PMID- 1917374 TI - Double jeopardy: psychopathology of black mentally ill returned migrants to Jamaica. AB - The psychopathology of 126 black Jamaican migrants who had spent an average of 12 years in North America and the United Kingdom and had subsequently returned to Jamaica, was established and compared to that of a matched control group of Jamaicans who had never migrated. There was a statistically significant difference in the pattern of diagnosis between the two groups (p less than 0.0001), and although the existence of a past history of mental illness between the groups was not statistically significant (p less than 0.1), the returned migrants had a significantly higher frequency of mental hospitalisation (p less than 0.0001) than the controls, with 94% of the previous hospitalisations of the returned migrants being for schizophrenic illnesses. Case studies are presented to illustrate the social stresses experienced by the returned migrant group in the countries to which they migrated and on the return to their home country, and thus to underscore the double jeopardy faced by these patients experiencing return migration. PMID- 1917375 TI - A comparison of taxonomic systems for classifying homeless men. AB - The present study compared the relative merits of two taxonomic systems for classifying homeless men. One system classified homeless men based on their past history of psychiatric disability. The other system classified individuals on the basis of their current psychiatric impairment. Both classification systems displayed significant discriminating power using a set of predictor variables that included demographic variables, childhood happiness, current life satisfaction, social support, stressful life events, and history of homelessness. Based on the percentage of correct classifications the system based on current impairment was superior to the system based on past history. PMID- 1917376 TI - The factor structure of the General Health Questionnaire in a Japanese high school and university student sample. AB - Factor structures of the 60- and 30-item versions of the General Health Questionnaire (GHQ) were explored, using data collected from 236 Japanese high school and university students. The 60-item version produced factors interpretable as social functioning, anxiety, somatic symptoms, and severe depression; the 30-item version produced general dysphoria, social functioning, depressive thoughts, difficulty in concentration and insomnia. Although the two versions of the GHQ produced the same number of factors, their structures differed in content. Thus it may be necessary to examine the factor structures of the GHQ when using it in a study of a population containing subjects with different cultural backgrounds. PMID- 1917377 TI - Control of calcium regulating hormones in the vertebrates: parathyroid hormone, calcitonin, prolactin, and stanniocalcin. PMID- 1917378 TI - Immunoarchitecture of regenerated splenic and lymph node transplants. PMID- 1917379 TI - Laser microbeam as a tool in cell biology. PMID- 1917381 TI - Molecular basis of cell cycle control in early mouse embryos. PMID- 1917380 TI - Observation of intracellular Ca2+ with aequorin luminescence. PMID- 1917382 TI - Cellular mechanisms of pattern formation in the developing limb. PMID- 1917384 TI - An experimental osteosarcoma of the athymic nude rat. AB - In this report we describe an experimental osteogenic sarcoma that had been radiation-induced on Sprague-Dawleys by Delbruck in 1980. We transplanted it to 120 athymic nude rats achieving take rates of 100%. The tumor doubling time was 10.5 days. The osteosarcoma on athymic rats thus proliferated extraordinarily well compared to other known models. Pulmonary metastases were demonstrated in 100% of the examined animals. Pathological examinations revealed morphological similarities to human osteosarcoma and no signs of anaplasia. PMID- 1917383 TI - Thromboxane production by platelets during tumor cell-induced platelet activation. AB - We have evaluated in a homologous system the mechanisms of platelet activation by cells isolated from fresh human tumor tissues and the role of thromboxane B2 (TxB2) generation in this process. Thirty-eight of the 46 tumor tissues considered showed a high platelet-aggregating activity, with no particular distribution in any specific tumor type. Apyrase caused a nonsignificant reduction in the aggregation response, hirudin did not change it, while iodoacetic acid or p-hydroxymercuriphenylsulfonate, specific cysteine proteinase inhibitors, significantly reduced the platelet-aggregating capacity of these tumor cells. In 9 colon carcinomas and in 8 breast carcinomas the levels of TxB2 produced by platelets after addition of tumor cells were measured: tumor cell induced platelet aggregation was accompanied by a significant production of the metabolite; indobufen, a cyclooxygenase inhibitor, significantly reduced aggregation and particularly TxB2 production, while the drug had no effect on both parameters if preincubated with tumor cells only. These data suggest that cells isolated from different human tumor tissues activate platelets through the activity of tumor-associated cysteine proteinase(s); platelet aggregation by tumor cells is largely dependent on arachidonic acid metabolism in platelets, while such metabolism in tumor cells does not play a significant role. PMID- 1917385 TI - Reduced metastatic ability of in vitro differentiated human rhabdomyosarcoma cells. AB - We studied the human embryonal rhabdomyosarcoma cell line RD and 8 derivatives obtained in our laboratory either by cell cloning or by culturing in vitro cells from tumors or secondaries grown in nude mice. The expression of desmin and of the embryonic isoform of myosin and the formation of multinuclear myotube-like structures were studied as specific markers of myogenic differentiation. During continuous growth, each derivative contained a proportion (ranging from 5 to 80% among derivatives) of desmin-positive cells and a small number of myosin-positive or multinuclear elements. Cells from continuous cultures were injected intravenously in nude mice, producing lung and kidney/adrenal nodules. No correlation was found between the proportion of cells expressing desmin and metastatic capacity. When cultures were grown in differentiation medium (Dulbecco's minimal essential medium + 2% horse serum) some derivatives (designated type A) showed a strong increase in the proportion of myosin-positive cells, while others (type B) showed no increase. In vitro differentiation significantly reduced the metastatic ability of type A cells, while no modification was observed in type B after growth in differentiation medium. The proliferative ability of type A and type B cells grown in differentiation medium did not correlate with the proportion of myosin-positive cells, and extensive formation of multinuclear myotubes was never observed. It was concluded that reduction of experimental metastatic ability was mediated by events related to late, though not necessarily terminal, differentiation of rhabdomyosarcoma cells. PMID- 1917386 TI - Invasion and metastasis, a recurring theme in multiple fields. PMID- 1917387 TI - Effects of synthetic peptides and protease inhibitors on the interaction of a human ovarian cancer cell line (NIH:OVCAR-3) with a reconstituted basement membrane (Matrigel). AB - We have investigated the adhesive properties and invasiveness of cells of the human ovarian carcinoma line, NIH:OVCAR-3, in vitro. OVCAR-3 cells exhibited a similar rate of adhesion to all substrates tested including laminin, fibronectin, and collagens I and IV. The synthetic peptide YIGSR-NH2, which corresponds to an attachment site in laminin, inhibited the adhesion of the cells to laminin, but not to fibronectin. In contrast, a GRGDS-NH2 peptide blocked adhesion to fibronectin but not to laminin. OVCAR-3 cells invaded and formed branched colonies on Matrigel. Colony formation was retarded by both YIGSR-NH2 and GRGDS NH2 peptides. Serine protease inhibitors and human recombinant TIMP, the tissue inhibitor of metalloproteases, inhibited ovarian tumor cell invasion while a synthetic collagenase IV inhibitor (SC-44463) had no effect. These studies suggest that metalloproteases other than collagenase IV may be important for the invasive activity of ovarian cancer cells. It is possible that synthetic peptides with antiadhesive cellular activity and certain antiproteases could be used to control the progressive colonization and invasion of peritoneal surfaces by malignant ovarian cancer cells. PMID- 1917388 TI - Cultured retinal pigment epithelium cells from donors with type I diabetes show an altered insulin response. AB - Retinal pigment epithelium (RPE) isolated from 13 of 49 eyes of donors with insulin-dependent diabetes produced viable, proliferating cultures. No difference was found in baseline glucose uptake and lactate production, as measured by 13C and 1H nuclear magnetic resonance, between the RPE cells from diabetic donors and those cultured from normal donors. Insulin-mediated stimulation of glucose uptake and lactate production was decreased significantly in the RPE cells from diabetic donors compared with those from normal controls. Oxygen consumption and the percentage of endogenous oxygen consumption from fatty-acid oxidation, determined by using a specific inhibitor, were similar in both groups. Cellular proliferation and endocytosis, measured by liposome uptake, also were stimulated by insulin similarly in both types of cells. These results show that at least one or more mechanisms of insulin action in the RPE, thought to be a noninsulin dependent tissue, may be altered permanently by chronic insulin-dependent diabetes. This finding may have implications for the pathogenesis of disease in noninsulin-dependent tissues even in patients with tight glycemic control. PMID- 1917389 TI - Blood-retinal barrier breakdown investigated by real-time magnetic resonance imaging after gadolinium-diethylenetriaminepentaacetic acid injection. AB - Recent magnetic resonance imaging (MRI) studies show that gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) entry into the vitreous space can be used as a qualitative marker of blood-retinal barrier (BRB) disruption. To determine if a more quantitative measurement of BRB breakdown could be obtained, the utility of acquiring real-time, T1-weighted proton images was studied after Gd-DTPA injection. Two days before the MRI experiment, panretinal photocoagulation was done. The mean signal intensity over selected regions-of interest (ROI) in the vitreous and anterior chamber was followed before and after (0, 10, 20, 30, 45, and 60 min) Gd-DTPA injection (1.0 mmol/kg, intravenously). At every laser power setting used in this study (0, 200, 400, 600, and 800 mW), the change in the mean signal intensity could be approximated by a simple exponential equation. However, the time constants determined for these curves were too imprecise to be useful as correlates between laser power and BRB breakdown. The slope of the line fit to the data in the first 20 min postinjection (ie, an initial-rate analysis) was a more precise correlate between BRB breakdown and laser power. This slope represented the rate of change in mean signal intensity in the ROI as a result of the entry of Gd-DTPA, and it was called the "leakiness" parameter. The leakiness parameter reflected changes in the permeability surface area product of the BRB if the blood flow and the Gd DTPA arterial concentration immediately after injection were approximately the same between animals. PMID- 1917390 TI - Prenatal ethanol exposure alters scotopic and photopic components of adult rat electroretinograms. AB - Ocular malformations and visual deficits are pathognomic of fetal alcohol syndrome (FAS). However, there are no reports on retinal visual function. To determine if prenatal (human second-trimester equivalent) or prenatal plus 10 days of postnatal (human third-trimester equivalent) ethanol exposure produced scotopic and/or photopic deficits in adult hooded rats, electroretinography (ERG) was used to examine rod and cone, increment threshold, dark adaptation, and paired-flash amplitude recovery functions. The rhodopsin content per eye also was determined. Five main results were found. First, voltage-log intensity and latency-log intensity functions, generated from single-flash ERGs in fully dark adapted rats, showed increases in absolute threshold and latency and decreases in response amplitude. Second, cone ERGs had latency increases. Third, there were decreases in the scotopic and photopic critical flicker-fusion frequencies, increment threshold functions, and absolute and relative refractory periods. Fourth, rod sensitivity, range, and rate of dark adaptation were decreased. Fifth, rhodopsin content per eye was decreased. These data showed that prenatal ethanol exposure produces long-term deficits in retinal sensitivity, amplitude, light and dark adaptation, temporal processing, and excitability. Larger deficits occurred in the scotopic than photopic system and were produced with an additional 10 days of postnatal ethanol exposure. Alterations in photoreceptors and other cells of the distal retina probably contributed to these deficits. The relevance and applicability of these data to FAS and subclinical alcohol embryopathy have yet to be demonstrated; however, they suggest that similar retinal alterations may occur in human FAS. PMID- 1917392 TI - Liposome suppression of proliferative vitreoretinopathy. Rabbit model using antimetabolite encapsulated liposomes. AB - The effects of the antimetabolites, cytarabine (Ara-C) and 5-fluorouridine 5' monophosphate (FUMP), encapsulated in multivesicular liposomes on formation of vitreous fibroproliferative membranes in New Zealand white (NZW) rabbits were studied. In pharmacokinetic studies, the drug half-life in the vitreous cavity was 124 hr after intravitreal administration of 1.0 mg of FUMP in liposomes. By contrast, the drug half-life after a single injection in nonliposome-treated controls was only 4.5 hr. In a heterologous dermal fibroblast model of proliferative vitreoretinopathy (PVR), there was a 92% decrease in frequency of tractional retinal detachments in rabbits receiving a single intravitreal injection of liposome-encapsulated 0.1 mg of FUMP compared with controls receiving liposomes without drug. A dose of 1 mg of Ara-C in liposome-treated rabbits was associated with only a 46% reduction in tractional detachment compared with controls. Multivesicular liposome-encapsulated FUMP may be useful for inhibiting formation of fibroproliferative membranes in the vitreous after vitreoretinal surgery. PMID- 1917391 TI - Growth factor-induced cytosolic calcium ion transients in cultured human retinal pigment epithelial cells. AB - Growth factor-induced changes of cytosolic free calcium ion concentration ([Ca2+]i) and phosphatidylinositol (PI) turnover in cultured human retinal pigment epithelial (RPE) cells were studied, and their temporal relationship was compared. After a 24-hr serum depletion, RPE cells were loaded with fura-2/AM, and [Ca2+]i was analyzed using a digital imaging microscopy system. The resting [Ca2+]i in a single cultured human RPE cell was 153 +/- 1.5 nM (mean +/- the standard error of the mean [SEM], n = 105). The percentage of reactive cells that had Ca2+ transients induced by various growth factors were: epidermal growth factor, 18%; basic fibroblast growth factor (bFGF), 5%; nerve growth factor, 15%; platelet-derived growth factor (PDGF), 70%; insulin-like growth factor, 0%; fibronectin, 0%; insulin, 3%; and fetal bovine serum (FBS), 100%. The PDGF showed a peak concentration of 237 +/- 4.7 nM (mean +/- SEM, n = 67) and FBS, 774 +/- 34.5 nM (mean +/- SEM, n = 52). Chelation of the extracellular Ca2+ by EGTA made the resting and peak concentration lower. The Ca2+ transients occurred within 60 sec and lasted less than 5 min after the application of the growth factors. However, measurements of phosphoinositides in 24-hr serum-starved RPE cells revealed that growth factor-induced PI turnover was much slower than Ca2+ transients. In addition, FBS, bFGF, and PDGF increased the contents of inositol phosphate, inositol biphosphate, and inositol triphosphate (IP3) in RPE cells slowly up to 60 min except that PDGF showed a peak of IP3 at 15 min after stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917393 TI - Angiostatic steroids potentiated by sulfated cyclodextrins inhibit corneal neovascularization. AB - It is known that hydrocortisone can be converted to a potent angiogenesis inhibitor by coadministration with heparin or with a sulfated cyclodextrin. The activity of tetrahydrocortisol-S, a purely angiostatic corticosteroid, can be potentiated by beta-cyclodextrin tetradecasulfate as shown in this study. This drug "pair" and other pairs of corticosteroids and beta-cyclodextrin tetradecasulfate can be applied topically to inhibit corneal neovascularization. Endotoxin-induced corneal neovascularization in rabbits was treated with beta cyclodextrin tetradecasulfate coadministered with either: hydrocortisone, tetrahydrocortisol-S, or 6-alpha-fluoro-17,21-dihydroxy-16-beta-methyl-pregna 4,9(11),diene,3, 20-dione. When optimal ratios of steroid and cyclodextrin were used, neovascularization was reduced to 13%, 26%, and 28% of untreated controls for the three steroids, respectively. Hydrocortisone-cyclodextrin drug pairs suppressed virtually all inflammatory cell infiltration (induced by endotoxin), whereas tetrahydrocortisol-cyclodextrin pairs only partially reduced inflammation. These results demonstrate that corneal neovascularization and corneal inflammation are separable processes and that the neovascularization may be treated specifically using angiostatic steroids without inflammatory activity. PMID- 1917394 TI - Sustained-release endotoxin. A model for inducing corneal neovascularization. AB - The rabbit corneal pocket assay is one of the most frequently used systems for the study of angiogenesis. This model particularly is useful to identify stimulators of new blood vessel formation. More recently, however, interest in inhibitors of angiogenesis has grown, and several antiangiogenic agents have been identified. Investigations of angiogenesis inhibitors require a reliable model for the stimulation of neovascularization. One method was modified to produce corneal neovascularization by implanting into the rabbit cornea a sustained release polymer containing endotoxin (Escherichia coli lipopolysaccharide). The implant was prepared by mixing weighed quantities of endotoxin with ethylene vinyl acetate copolymer (Elvax) and forming 1-mm3 pellets containing 1%, 7.5%, 15%, 20%, 30%, and 40% (w/w) of endotoxin. Pure Elvax pellets were implanted as controls. Intrastromal corneal pockets were created in 92 eyes of male, albino New Zealand rabbits (n = 80), and sterilized endotoxin-copolymer implants were introduced. The growth rate of new vessels was measured by slit-lamp biomicroscopy. Endotoxin loads of 15% (n = 40) produced a strong neovascularization response with minimal stromal edema, with a mean growth rate of 0.21 +/- 0.12 mm/day. Loads of 1%, 7.5%, and 20% yielded 0.1 +/- 0.03 mm/day, 0.27 +/- 0.05 mm/day, 0.30 +/- 0.06 mm/day, respectively (n = 8, each group). Higher loads (30% and 40%; n = 8, each group) produced intense neovascularization, accompanied by severe corneal edema that obscured accurate measurement of the vessels. Corneal pockets that did not contain polymer implants were avascular. When endotoxin-Elvax pellets were removed, the new vessels regressed within 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917395 TI - Effect of interferon on a primary conjunctival epithelial cell model of trachoma. AB - An in vitro human primary conjunctival epithelial system was adapted to determine if the effects of interferon-gamma (IFN-gamma), as described in cultured cell lines, were applicable to human ocular infection with Chlamydia trachomatis, Primary human epithelial cell cultures were exposed to varying concentrations of IFN-gamma. The treatment resulted in the induction of the tryptophan decyclizing enzyme indolamine 2,3-deoxygenase (IDO) in a dose-dependent manner as determined by assaying the conversion of tryptophan to its metabolites using reversed-phase high-performance liquid chromatography. Little IDO induction occurred in the presence of IFN-alpha or IFN-beta. Catabolism of up to 38% of available tryptophan occurred in IFN-gamma-treated cells in contrast to controls that showed only baseline activity. Cells cultured with IFN-gamma and then infected with an ocular isolate of C. trachomatis (TW-5), had a reduction in the percentage of inclusion-containing cells by over 80% in a dose-dependent manner. Reversal by the addition of exogenous tryptophan substantiated that IFN-gamma mediated induction of IDO and catabolism of tryptophan were responsible for inhibition of intracellular growth of C. trachomatis. PMID- 1917396 TI - Temporal contrast sensitivity loss in primary open-angle glaucoma and glaucoma suspects. AB - The need for more sensitive tests for the early detection of compromised visual function in glaucoma is established by anatomic and psychophysical evidence of damage occurring to optic nerve fibers in eyes with normal visual fields. The results are reported of temporal frequency testing on 51 glaucoma suspects without visual field loss in either eye, 52 glaucoma patients with visual field deficits in the tested eye, and 11 normal subjects. Modulation transfer functions were obtained using a sinusoidally flickering 5 degrees spatially uniform white field viewed with central fixation and plotted at six frequencies from 5-30 Hz. The results showed a frequency-specific sensitivity loss centered at 15 Hz and a nonfrequency-specific mean sensitivity loss, that was greater, on average, in glaucoma patients than in suspects. Sensitivity losses of both kinds were seen in most glaucoma patients, but only in a minority of glaucoma suspects. About 12% of suspects were indistinguishable from the lowest performing one third of these glaucoma patients. A smaller number of suspects appeared to form a second mode in the frequency distribution for temporal sensitivity at 15 and 25 Hz. In patients with glaucoma, age was found to be a significant factor associated with the magnitude of mean sensitivity loss. Age was not a significant factor contributing to sensitivity loss in individual suspect data as measured by regression analysis, but it contributed to a small and consistent sensitivity loss across frequency for group-averaged data in those older than 55 years of age. PMID- 1917397 TI - Parapapillary atrophy and retinal vessel diameter in nonglaucomatous optic nerve damage. AB - Parapapillary chorioretinal atrophy and decreased retinal vessel diameter occur in glaucomatous eyes. To evaluate the frequency and degree of these signs in nonglaucomatous optic neuropathy, the authors evaluated morphometrically and compared 47 patients with nonglaucomatous optic nerve atrophy from extraocular causes with 292 patients with primary open-angle glaucoma and 179 normal subjects. Eyes with anterior ischemic optic neuropathy were excluded. The parapapillary atrophy was differentiated into a central zone (beta) with sclera and large choroidal vessels visible by ophthalmoscopy and a peripheral zone (alpha) with irregular pigmentation. Both zones did not differ significantly in the eyes with nonglaucomatous optic neuropathy and the normal eyes. In the glaucomatous eyes, they were significantly larger and occurred more frequently. The retinal vessel diameter was significantly smaller in both groups with optic nerve atrophy than in the normal group. It was concluded that decreased retinal vessel diameters unspecifically suggest optic nerve atrophy. Evaluation of parapapillary chorioretinal atrophy can be helpful in differentiating nonglaucomatous from glaucomatous optic neuropathy. PMID- 1917398 TI - Pharmacokinetic basis for nonadditivity of intraocular pressure lowering in timolol combinations. AB - The authors determined whether the ocular absorption of topically applied timolol in the pigmented rabbit was affected significantly by coadministration with either pilocarpine or epinephrine in the same drop to explain the nonadditivity in intraocular pressure lowering (IOP) seen clinically. They instilled 25 microliters of 0.65% timolol maleate solution (equivalent to 0.5% timolol), both in the presence and absence of 2.6% pilocarpine nitrate or 1% epinephrine bitartrate, into pigmented rabbit eyes. The time course of timolol concentration in the conjunctiva, anterior sclera, corneal epithelium, corneal stroma, aqueous humor, iris-ciliary body, and lens was monitored for 360 min by using reversed phase high-performance liquid chromatography. The area under the timolol concentration-time curve in all but one of the anterior segment tissues was reduced by 20-50% (mean, 40%) when timolol was coadministered with pilocarpine and by 20-70% (mean, 42%) when timolol was coadministered with epinephrine. Such an effect was not a result of alterations in corneal permeability or aqueous humor turnover rate, nor was it related to the extent of systemic absorption caused by pilocarpine and epinephrine. Rather, the reduction in ocular timolol absorption may have been caused by the accelerated washout of timolol by tears stimulated by the coadministered drugs and, to a lesser extent, by the loss of timolol through binding to the increased amount of tear proteins induced by the coadministered drugs. Thus, the nonadditivity in IOP lowering from timolol pilocarpine and timolol-epinephrine combinations is probably caused by changes in precorneal timolol clearance. PMID- 1917399 TI - Effects of acetylcysteine on rabbit conjunctival and corneal surfaces. A scanning electron microscopy study. AB - Conjunctival and corneal epithelial surfaces of normal rabbit eyes with their associated mucus were studied by scanning electron microscopy before and after treatment with the mucolytic agent N-acetylcysteine (AC). Four groups received topically one 50-microliters drop of either (Group A) 0.1 MAC, (Group B) 0.1 M AC every 5 min for 1 hr, (Group C) 0.1 M AC every 5 min for 2 hr, or (Group D) three drops of 20% AC over 15 min. The effects of the instillation of AC on mucus removal and cellular lesions increased in the order (A) less than (B) less than (C) less than (D). Treatment A had no effect on cornea and conjunctiva. Treatment B cleaned away mucosal debris without alteration of either conjunctival or corneal epithelium. Treatment C had a similar effect on the mucus but was associated with focal necrosis, and treatment D produced widespread necrosis, desquamation of epithelial cells, and inflammation. PMID- 1917400 TI - Interferon-gamma inhibits collagen synthesis by human Tenon's capsule fibroblasts in vitro. AB - Collagen deposition is largely responsible for scar information, an undesirable outcome of glaucoma filtering surgery. Because interferon-gamma (IFN-gamma) has been reported to inhibit collagen synthesis in a variety of cells, the authors examined its effect on collagen synthesis by Tenon's capsule fibroblasts cultured from three patients. In addition, the authors studied the effects of IFN-gamma on fibroblast proliferation. IFN-gamma inhibited collagen synthesis at dosages of 1 10,000 U/ml. The average median effective dose (ED50) was 6.60 U/ml. In contrast, IFN-gamma had no significant effect on cell proliferation in dosages of 0.001 10,000 U/ml. These results suggest that IFN-gamma may be a useful agent for modifying the wound healing response, particularly after glaucoma filtering surgery. PMID- 1917401 TI - The role of tetracycline in chronic blepharitis. Inhibition of lipase production in staphylococci. AB - Tetracycline administered in low doses can be effective in the long-term management of patients with meibomian keratoconjunctivitis (MKC). However, the mechanism of action does not appear to be a reduction of bacteria. Seventy-five percent of the ocular staphylococci in such patients are resistant to tetracycline. An alternative mechanism of action could be the inhibition of production of extracellular enzymes by the ocular flora. Inhibition of lipase production could result in lowered levels of toxic hydrolysis products (free fatty acids), which may exacerbate the disease process. The authors tested this hypothesis by examining the differential effect of tetracycline on growth and lipase production in a tetracycline-resistant and tetracycline-sensitive strain of Staphylococcus epidermidis and S. aureus isolated from patients with MKC and Staphylococcal blepharitis. Tetracycline caused significant decreases in the production of lipase in the sensitive and resistant strains of S. epidermidis without concominant decreases in growth. In contrast, S. aureus strains showed parallel decreases in both lipase production and inhibition of growth. The authors propose that the sensitivity of lipase production to tetracycline, in tetracycline-resistant S. epidermidis, may partially explain the clinical improvement observed in MKC patients. PMID- 1917402 TI - The linearity of proximally induced accommodation and vergence. AB - This study sought to determine the linearity and amplitude of both proximally induced accommodation (PIA) and vergence (PIV) by comparing the open-loop accommodation and vergence responses, respectively, to individual stimuli located at viewing distances ranging from 0.20 m to 1,500 m. For the measurement of PIA, the vergence and accommodation loops were opened by subjects (N = 10) monocularly viewing the target through a 0.5-mm pinhole, while accommodation was assessed concurrently using an infrared optometer. In the assessment of PIV, the accommodation loop was opened either by subjects (N = 10) viewing a low-frequency difference of Gaussian (DOG) grating or by viewing the targets binocularly through 0.5-mm pinholes. For both PIV methods, the vergence loop was opened by vertical dissociating prisms while the heterophoria was assessed for the various target distances using the von Graefe technique. The results demonstrated significant changes in both PIA and PIV for stimuli located closer than 3 m. However, both proximal components attained a minimum level and remained constant for targets at or beyond 3 m. Furthermore, the magnitudes of PIA and PIV were linearly related to the target distance measured in diopters and meter angles, respectively. These findings clearly demonstrate the influence of target proximity on the oculomotor system. PMID- 1917403 TI - Accuracy of topographic measurements in a model eye with the laser tomographic scanner. AB - The authors evaluated the accuracy of topographic measurements with the laser tomographic scanner using a model eye. Diameter, depth, and shape at different axial lengths of four sample holes that simulated optic nerve heads in phakic and aphakic conditions were determined by confocal imaging. The computer-generated cross-section profiles of the simulated optic nerve heads corresponded well with the actual contours as photographed by scanning electron microscopy. The average relative error in diameter was 2.0% (range: 0.3-2.9%) for the phakic model eye and 3.6% (range: 0.6-8.2%) for the aphakic model eye. The average relative error in depth was 11.7% (range: 1.2-20.1%) for the phakic model eye and 10.1% (range: 1.7-22.6%) for the aphakic model. PMID- 1917404 TI - Testosterone-induced suppression of autoimmune disease in lacrimal tissue of a mouse model (NZB/NZW F1) of Sjogren's syndrome. AB - The current investigation was designed to examine whether androgen administration might suppress autoimmune disease in lacrimal glands of a mouse model (NZB/NZW F1) of Sjogren's syndrome. Autoimmune, female mice were treated with vehicle or varying concentrations of testosterone for 0, 17, 34, or 51 days, and tears, lacrimal glands, as well as submandibular tissue, were collected from killed mice after androgen exposure. Glands were histologically processed and evaluated with a computer-assisted image analysis system. Results showed that testosterone administration induced a significant, time-dependent decrease in the extent of lymphocytic accumulation in the lacrimal gland. After 34-51 days of androgen therapy, the magnitude of lymphocyte infiltration had been suppressed 22- to 46 fold, compared with that in placebo-treated tissue. This hormone effect was associated with significant reductions in the number of focal infiltrates, the area of individual foci, and the total quantity of lymphocyte infiltration per lacrimal section. Testosterone exposure also stimulated an increase in lacrimal gland weight and a rise in tear volumes, relative to those measured in the same mice before treatment. In addition, androgens significantly diminished the extent of lymphocyte accumulation in submandibular tissue. In summary, our results demonstrate that androgen administration may inhibit the progression of autoimmune disease in lacrimal and submandibular glands of NZB/NZW F1 mice. PMID- 1917405 TI - Magnetic resonance chemical shift imaging and spectroscopy of atherosclerotic plaque. AB - An in vivo magnetic resonance imaging (MRI) technique for identification and characterization of atherosclerotic plaque was assessed in animal and human models. Atherosclerosis was induced in the abdominal aorta of four rabbits by a combination of balloon denudation and a high cholesterol diet. In vivo conventional spin-echo and fat/water suppressed images of the rabbit aortae were obtained at 1.5 T. Chemical shift imaging (CSI) was achieved using a hybridization of selective excitation and modified Dixon techniques. These techniques were then used to obtain images of atherosclerotic lesions in the carotid arteries of four patients prior to endarterectomy. The MRI results were corroborated by histologic and high-resolution proton MR spectroscopic (8.5 T) analysis of rabbit aorta, human carotid endarterectomy, and six additional human superficial femoral and iliac atherectomy specimens. All animal and human lesions were classified as either fatty streaks or fibrotic plaque. When compared to conventional spin-echo images, fat suppression by CSI substantially improved the measured contrast-to-noise ratio between plaque and vessel lumen, and enhanced its discrimination from periadventitial fat. In contrast, water suppression eliminated visualization of plaque due to the negligible amount of isotropic (liquid-like) signal from the immobilized lesion lipids. Magnetic resonance spectroscopy corroborated the CSI results by demonstrating broad, ill-defined fat resonances characteristic of nonmobile lipids in both human and rabbit atherosclerotic lesions. These findings indicate that in vivo MRI of plaque is technically feasible and can be markedly improved using chemical shift imaging. PMID- 1917406 TI - The effects of iodixanol and iopamidol on hemodynamic and cardiac electrophysiologic parameters in vitro and in vivo. AB - Iodixanol is a new, nonionic, dimeric contrast medium which, in concentrations appropriate for radiographic use, is hypotonic with respect to plasma. The purpose of these in vivo and in vitro studies was to compare the effects of iopamidol, iodixanol formulated to isotonicity with sodium salts (sodium formulation), and iodixanol formulated to isotonicity with sodium, calcium, and magnesium salts (cationic formulation) on hemodynamic and electrophysiologic parameters. In vitro, the spontaneous rate of contraction by guinea pig right atrial and force development by right ventricular papillary muscles were evaluated in the presence of 1% to 100% (v/v) of the three contrast media. Iopamidol significantly (P less than .05) decreased the rate of atrial contraction to a greater extent than either formulation of iodixanol. Iopamidol decreased papillary muscle force development more than the sodium formulation of iodixanol (P less than .05). The cationic formulation of iodixanol had little effect (less than 30% change) on papillary muscle force development at concentrations up to 100%. The contrast media were also injected into the left coronary arteries of open-chest, anesthetized dogs at 0.8 mL/second for 5 to 30 seconds. All contrast media increased (P less than .05) systolic blood pressure (SBP), mean arterial pressure (MAP), and peak left ventricular pressure (LVP). Iopamidol increased LVP and LV end diastolic pressure to a greater extent (P less than .05) than the cationic formulation of iodixanol. We conclude that iopamidol affected cardiovascular parameters more than iodixanol. PMID- 1917407 TI - Ultrasonographic estimation of fetal body composition for children of diabetic mothers. AB - The authors hypothesized that ultrasound-generated measurements of the fetus could be used to predict body composition for children of diabetic mothers. Seven ultrasonically identifiable fetal morphometric parameters were measured on 21 fetuses of diabetic mothers within 7 days of delivery. These seven individual measurements were then matched to neonatal morphometric estimations of body composition by means of stepwise regression analysis. Ultrasound variables which were found to show significant correlation to the newborn estimates of body composition were combined to generate an equation that could predict neonatal lean body mass and fat mass. Neonatal lean body mass could be predicted with R = .93 (P less than .001, 95% confidence limits .80-.98). Neonatal fat mass could be predicted with R = .81 (P less than .001, 95% confidence limits .55-.92). Prospective evaluation of the regression equations in an additional 18 patients showed no significant difference between ultrasound-predicted body composition and newborn morphometric estimation of body composition. The authors conclude that estimations of fetal body composition are possible, and may provide a valuable tool in the identification of fetal growth abnormalities. PMID- 1917408 TI - Carpo-metacarpal growth disturbance and the assessment of carpal narrowing in children with juvenile rheumatoid arthritis. AB - Second metacarpal length (M2), radio-metacarpal length (RM), and intermetacarpal width (W) were measured on 96 radiographs in 52 children with polyarticular juvenile rheumatoid arthritis (JRA), and compared with body height and skeletal maturation in order to: (1) differentiate between processes resulting in retardation of bone growth and those producing delay in skeletal maturation; (2) assess the severity and progression over time of such retardation; and (3) assess the impact of retardation of the second metacarpal on the assessment of carpal narrowing in children with JRA. All measurements were converted into z scores (the units of standard deviation above or below the normal mean for each measurement) based on published norms. Retardation of M2 (mean z scores -0.91) began earlier and was more severe compared with retardation of height (mean z score -0.25). This disproportion widened with increasing duration of disease. That this primarily represents a disturbance in M2 growth rather than a secondary effect due to altered maturation is suggested by the bone ages being normal (mean z score 0.14) and the absence of premature closure of the metacarpal physes. Z scores for RM/W (mean -3.53) were at least 1 Z more negative than for corresponding measurements of RM/M2 (mean -2.41) in 47 (90.4%) children and the mean difference between the z scores for RM/W was -1.12. This discrepancy between RM/W and RM/M2 was eliminated by correcting for the reduction in M2. PMID- 1917410 TI - The effects of ioxaglate 320, iohexol 350, and iopamidol 370 on erythrocyte aggregation. AB - The authors report a randomized, double-blind prospective trial comparing the effects of nonionic with ionic low-osmolar contrast media on erythrocyte aggregation. The study group comprised 40 consecutive patients with pathology necessitating selective angiography. Patients were examined using either ioxaglate 320, iohexol 350, or iopamidol 370. Erythrocyte aggregation was assessed both macroscopically and microscopically. Erythrocyte aggregation occurred more frequently in the iopamidol group (13 of 45 samples examined) than in the iohexol (4 of 46) or ioxaglate (5 of 51) groups (P = .002). PMID- 1917409 TI - Gd-DTPA-enhanced short repetition time and short inversion time inversion recovery magnetic resonance imaging. Experimental and clinical assessment. AB - To suppress both water and fat signal while retaining the high signal of Gd-DTPA enhancement, magnetic resonance imaging (MRI) of phantoms and 28 patients with mass lesions was done using short repetition time (TR) and short inversion time inversion recovery (STIR) sequences. Optimal STIR pulse sequences of 500 to 1000/80-100/20-30 (TR/TI/TE) were determined by an experimental study. In most instances, a signal bandwidth of +/- 8 kHz was used to increase the signal-to noise ratio. The authors measured image contrast between lesions and adjacent fatty tissue and compared postcontrast STIR and T1-weighted spin-echo (T1-W SE) images. When the signal intensity of a lesion is 80% of adjacent fatty tissue on postcontrast T1-W SE, short TR STIR images provide better tumor delineation. PMID- 1917411 TI - Effect of lidocaine on the meninges in an experimental animal model. AB - Arachnoiditis has been reported in patients who had received previous epidural injections of anesthetic agents. The purpose of this study was to determine if epidural injections of lidocaine are sufficient to cause arachnoiditis. Four monkeys that received a single epidural injection of lidocaine hydrochloride 1% were compared to four controls that had epidural injections of 0.9% saline. Four dogs that had multiple epidural injections of lidocaine hydrochloride 1% were compared to four controls that had multiple injections of saline. All animals were killed on the eighty-fourth day of the experiment. The dural sac, containing nerve roots and spinal cord, was removed intact from the lumbar spinal canal, fixed, sectioned, stained, and examined microscopically for evidence of arachnoid inflammation and fibrosis. No significant changes were found in the treated animals. Lidocaine hydrochloride 1% injected singly or repeatedly in the epidural space does not appear to be a cause of significant chronic meningeal reaction. PMID- 1917413 TI - The lure of academic radiology. PMID- 1917415 TI - Training and postgraduate examinations in radiology in Australasia. PMID- 1917414 TI - Correlative imaging in radioimmunotherapy. PMID- 1917412 TI - In vitro evaluation of a mechanical injector for infusion of magnetic resonance contrast media. AB - The authors evaluated the performance of a prototype mechanical injector developed for infusion of magnetic resonance (MR) contrast media. The injector was installed in a 0.6-T clinical MR scanner, and evaluation was made using saline (viscosity: 1.0 cP) and gadopentetate dimeglumine (viscosity: 4.9 cP) with 16-, 21-, and 25-gauge needles, and 244- and 366-cm connecting tubing. At a fixed flow rate of 1 mL/second, volume infused was within 10% of the desired volume except for infusions less than 1 mL. Reproduction of flow rates was less reliable. With saline, maximal flow rates were 5.5 mL/second, 4.2 mL/second, and 1.1 mL/second for the 16-, 21-, and 25-gauge needles, respectively, and 3.7 mL/second, 2.4 mL/second, and 0.9 mL/second, respectively, for gadopentetate dimeglumine. Needle size was identified as the major factor limiting flow rate. The magnet was reshimmed after the injector was installed, and no deleterious effects were identified on gradient echo (TR: 250/TE:18/flip angle 60 degrees) MR images. PMID- 1917416 TI - Understanding complex images. Perspectives from visual cognition. PMID- 1917417 TI - Bone and soft tissue lesions: diagnosis with combined H-1 MR imaging and P-31 MR spectroscopy. PMID- 1917418 TI - Results of the 1990 survey of the American Association of Academic Chief Residents in Radiology (A3CR2) emphasizing data about chief residents in radiology. PMID- 1917419 TI - Oesophageal pH monitoring. PMID- 1917420 TI - The role of 3 hour distal oesophageal pH monitoring in gastro-oesophageal reflux. AB - It has been suggested in the literature that an eight hour period of distal oesophageal monitoring is adequate for the diagnosis of reflux in symptomatic patients. The aim of this study was to investigate whether 3 hour intra oesophageal pH-metry could be substituted for the eight hour test period without loss of sensitivity in the diagnosis of GOR. Twenty patients were tested, 10 of whom had classical De Meester symptoms of GOR and 10 asymptomatic patients served as controls. All were commenced on 3 hour ambulant pH monitoring of the distal oesophagus. This was followed by a separate period of 8 hour testing. Each test had a 50% supine time period. The following variables were determined: (i) number of reflux episodes (ii) number longer than 5 minutes (iii) longest episode of reflux, (iv) percent of time that pH was below 4. Results are analysed using the 'Esophogram' computer program. 8 hour monitoring resulted in a positive diagnosis of GOR in 10 of 10 patients, giving an overall sensitivity of 100%. 3 hour testing was positive in 8 patients (sensitivity of 80%). The best correlations were obtained when comparing total reflux episodes, and the percent of total time pH less than 4, but overall the tests correlate poorly for individual variables. None of the controls had positive 3 or 8 hour testing. We conclude therefore, that 3 hour pH metry may be a useful screening test to confirm symptomatic reflux, and can be performed within a single clinic visit. If negative, arrangements must be made for more prolonged monitoring. PMID- 1917421 TI - Neuroleptic malignant syndrome--follow-up study. PMID- 1917423 TI - Front crawl drowning following previous syncopal episodes. PMID- 1917422 TI - Broncho-oesophageal fistula of infectious origin. AB - A case of end stage pulmonary destruction secondary to adult onset broncho oesophageal fistula of infectious aetiology is presented. Advanced bronchiectatic damage to the pulmonary parenchyma may be avoided by the maintenance of a high index of suspicion and a systematic approach to the diagnosis of recurrent lower respiratory tract infections. PMID- 1917425 TI - Gm typing of Irish coeliac patients and controls does not help locate the "second" coeliac gene. AB - A two gene model has been proposed to explain the inheritance of coeliac disease (CD). One gene is on chromosome 6 in the MHC complex (HLA associated). It has been suggested the second gene is located on chromosome 14, in or near the region encoding for immunoglobulin heavy chain allotypes (Gm types). In a study of 102 unrelated Irish coeliacs and a group of ethnic controls, we have failed to show an association of CD with any particular Gm type or types. There is no evidence to confirm that a gene on chromosome 14 is implicated in the inheritance of CD. PMID- 1917424 TI - Pharmacogenetics and drug metabolism: an Irish perspective. AB - Genetic factors, particularly in relation to control of liver drug metabolism, are a major cause of variability in the response to drugs. In 145 Irish subjects 48% were fast acetylators of sulphadimidine in contrast to 80% in Chinese subjects. Eleven (7.6%) of our Irish population showed an improved ability to oxidise delrisoquine. The therapeutic implications of these findings are discussed. PMID- 1917426 TI - High level penicillin resistant Streptococcus pneumoniae. PMID- 1917427 TI - Medication and the management of infantile gastroenteritis. PMID- 1917428 TI - Antineutrophil antibodies (ANCA) PMID- 1917429 TI - Thromboblastic hyperthyroidism: sensitive monoclonal TSH assay demonstrates suppressed immunoreactive TSH. AB - We describe a case of frank clinical hyperthyroidism due to hydatidiform mole. This is thought to be due to human chorionic gonadotrophin (hCG) or a closely related molecule produced by the tumour. hCG can cross-react with TSH in older TSH radioimmunoassays causing falsely elevated TSH levels. We demonstrate this does not occur with a chemiluminescent immunometric (monoclonal) TSH assay despite circulating hCG levels greater than 10(6) u/L. PMID- 1917430 TI - A preventable cause of tracheal injury at oesophagectomy. AB - Advocates of transhiatal oesophagectomy warn of the danger of tracheal injury resulting from the blind dissection of tumours of the upper and middle thirds of the oesophagus when the tumour has invaded the membranous part of the trachea. We report an unusual cause of tracheal injury at transhiatal oesophagectomy due to dissection at the level of the inflated endotracheal cuff in a patient with a tumour at the gastro-oesophageal junction. PMID- 1917431 TI - Chemical pathology out-of-hours services in Beaumont and Blanchardstown hospitals following the introduction of continuous accident and emergency cover for local catchment areas. AB - The effect on the Chemical Pathology 'on-call' services at Beaumont and Blanchardstown hospitals of the change in the Accident and Emergency service from a regular roster covering the northern half of Dublin to continuous local catchment area cover is reported. At Beaumont, the number of patient specimens each night from the A&E department is similar to the peak level which occurred approximately every third day under the old rota system. The total continuous demand in the hospital is about 10% higher than the previously reported peak demand. At Blanchardstown by contrast, the demand from A&E has fallen by about 60% from the previous peak but services to inpatients have increased by 50% over the previous year's published figure. Thus the on-call demands for Chemical Pathology services continue to grow but there has been a large shift in demand towards the hospital with the greater catchment area. PMID- 1917432 TI - Carcinoid tumour of the larynx: a case report and clinico-pathological review. AB - Carcinoid tumour of the larynx is a rare condition but one that is being increasingly recognised. We report the case of a 66 year old lady with an advanced malignant laryngeal carcinoid, metastasizing to the regional lymph nodes, thyroid and submandibular glands. Surgery is the treatment of choice in this condition--radiotherapy and chemotherapy being ineffective. Prognosis is poor, and most patients eventually die of distant metastases. The clinical, biochemical and histological findings are reviewed. PMID- 1917433 TI - The microbial flora of in-use blood pressure cuffs. AB - The capacity of blood pressure cuffs to act as vehicles of hospital infection has been recognised. We describe the microbial flora of in-use DINAMAP blood pressure cuffs used in the operating theatres and one recovery room in a teaching hospital. Our results show significant microbial contamination of in-use blood pressure cuffs. PMID- 1917434 TI - Polycythaemia and neuroblastoma. AB - The treatment of primary proliferative polycythaemia (polycythaemia rubra vera) may include radioactive phosphorus (P32) in conjunction with venesection. Acute leukaemia or carcinoma can be associated with the use of P32. We present a case of primary proliferative polycythaemia treated by repeat venesection together with P32 whose follow-up was complicated by the development of malignant neuroblastoma. PMID- 1917435 TI - Reassessing Freud's case histories. The social construction of psychoanalysis. PMID- 1917436 TI - Nobelesse oblige: lives of molecular biologists. Essay review. PMID- 1917437 TI - Fate of intravenously injected aminated beta(1----3) polyglucose derivatized with 125I-tyraminyl cellobiose. AB - Aminated beta(1----3)glucan (polyglucose, AG), a potent soluble immunomodulator, was radio-iodinated and traced after intravenous administration to rats. Since the glucose polymer cannot be 125I-labelled directly by conventional methods, the polysaccharide had to be substituted with an adduct which binds the radiolabel. To this end, tyraminyl cellobiose (TC) was coupled to amino groups of AG by means of cyanuric chloride. This procedure resulted in a degree of substitution corresponding to 3.6% (or 1 molecule of tyraminyl cellobiose being incorporated per 28 molecules of glucose). AG substituted with TC (TC-AG) could be labelled with 125I by conventional procedures. After intravenous administration of 125I-TC AG the serum concentration dropped about 50% from 1 min to about 15 min after injection, while a further drop from 50% to about 25% was observed during the next 15-60 min. The finding that 60 min after injection most of the radioactivity was recovered in the kidneys and urine, together with the results from gel chromatography showing that the low Mw fraction of the injected material disappeared first from the circulation, suggests that the initial rapid phase of elimination is due mainly to glomerular filtration. The molecules that are too large for kidney excretion are taken up mainly by the liver (about 10% of injected dose) at a slower speed. This notion was supported by the finding that a preparation of high Mw glucan obtained by gel chromatography survived for a long period in the circulation, and was eliminated mainly by accumulation in liver, whereas a preparation of low Mw glucan was rapidly eliminated by glomerular filtration. Several days after injection the liver contained nearly 90% of the recovered radioactivity, whereas the kidneys and other organs contained only insignificant amounts. This indicates that radioactivity associated with the kidneys after 60 min reflects glomerular filtration, whereas radioactivity in liver results from uptake leading to lysosomal accumulation. Isolation of liver cells after injection disclosed that the radioactivity per cell was the same in Kupffer cells (KC) and liver endothelial cells (LEC), whereas the uptake per parenchymal cell (PC) was about 30% of the uptake per KC and LEC. It could be calculated that in the intact liver, the population of PC was responsible for 50% of the uptake, whereas the populations of LEC and KC contained 35% and 15%, respectively, of the total liver radioactivity. These findings raise the question whether not only KC, but also LEC and PC may be mediators of the immune responses caused by beta(1----3) polyglucose. PMID- 1917438 TI - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral immunity: I. Similarities to Staphylococcus aureus Cowan Strain I (SAC) in the in vitro T dependent antibody response. AB - We have determined that suppression of the in vitro T-dependent humoral immune response by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is dependent on the type and concentration of serum used in the culture media. Only five out of 23 commercial lots of serum (screened at both 5 and 10%) could support a suppression in the presence of 30 nM TCDD, with the remaining lots demonstrating an apparent 'protective-like' effect against the TCDD exposure. When log dose response curves were established with TCDD (0.3, 3.0, and 30 nM) in media containing each of the serum lots supporting a suppression (at both 5 and 10%), we determined that only three lots could support a full dose-responsive suppression. Subsequently, in a comparison study between the effects of TCDD and the polyclonal B-cell activator Staphylococcus aureus Cowan Strain I (SAC) on the in vitro T-dependent humoral immune response, we have found that SAC suppresses the antibody response to SRBC and demonstrates the same serum dependency for this effect as was previously noted for TCDD. Under serum-free culturing conditions, TCDD (30 nM) caused a 15 fold increase in the AFC response to SRBCs over controls, suggesting that direct addition of TCDD to whole splenocyte cultures in the absence of serum-derived growth factors results in an increase in B-cell activation. Likewise, under serum free conditions, SAC dose-dependently increased the AFC response over media controls, and at doses which achieved the same degree of suppression of the humoral response aa TCDD. Taken together, these studies suggest that TCDD has actions that are similar to a T cell independent polyclonal B cell activator such as SAC, and selectively acts on the B cell to suppress the T-dependent humoral immune response by a mechanism which is unique to this series of compounds. This effect however, is only detectable under appropriate serum-supported (or serum deficient) culture conditions as described. PMID- 1917439 TI - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral immunity: II. B cell activation. AB - Previous reports have indicated similarities in the actions of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) and the polyclonal B cell activator Staphylococcus aureus Cowan Strain I (SAC) on the in vitro T-dependent antibody response to SRBC. This finding has suggested that B cell activation is likely to be an important component in the direct effects of TCDD on lymphocyte function. In the current investigation, various techniques were employed to determine whether TCDD could cause the activation of splenic-derived dense resting B cells in the absence of antigen and to determine if the modulatory effect of serum derived growth factors is the result of a direct action on the B lymphocyte. TCDD (30 and 60 nM) caused an increase in proliferation of dense resting B cells at both 72 and 96 h following addition. This action of TCDD was demonstrated to possess a serum dependency that was based on the lot of serum in which the cells were cultured. Under similar conditions, TCDD (30 nM) stimulated an increase in total IgM secretion as measured on day 7 of culture. A similar profile of activity was observed in vivo, where splenic-derived dense resting B cells from animals treated with 1 microgram/kg TCDD for 5 days, but unsensitized to SRBC, demonstrated a 10-fold increase in proliferation on day 3 of culture which likewise occurred in a serum dependent manner. In addition, we observed that mice treated with 1 microgram/kg TCDD for 5 days and sensitized with SRBCs, sustained a complete loss in their splenic-derived dense B cell populations (day 4 after sensitization). The loss of this B cell population is indicative of a movement of these cells into a blastogenic state of activation and is not observed in matched corn oil-treated controls. These findings support our previous observations and give evidence that TCDD is capable of causing the direct activation of resting B cells. This activation is dependent on the type of serum present during in vitro culture and appears to be intensified in the presence of antigen in vivo. PMID- 1917441 TI - Taxation without representation. PMID- 1917440 TI - Drug-mediated increase of susceptibility of human lung cancer to NK or LAK effector cells. AB - Previous studies in murine models have shown that in vivo or in vitro treatment of tumor cells with mutagenic triazene compounds (TZC) lead to the appearance of novel drug-mediated tumor antigens (DMTA) capable of eliciting graft resistance in syngeneic hosts. This phenomenon, defined as 'chemical xenogenization' (CX), could be of potential value for immunochemotherapy of human neoplasias. It was also shown that TZC modulate NK sensitivity of murine tumor cells. Therefore, experiments were conducted to evaluate whether susceptibility of a human lung adenocarcinoma cell line (H125) to natural cytotoxic effectors could be affected by treatment with an in vitro active TZC. The results showed that drug treatment of H125 line leads to heritable increase of susceptibility to NK and LAK cells. Moreover, increased binding between effector and drug-treated target cells was observed. Additional studies on HLA antigens showed that changes in HLA-ABC molecule expression were probably not involved in TZC-induced increase of NK/LAK susceptibility. These results suggest that TZC treatment of a human tumor could result in increased expression of membrane structures recognized by natural cytotoxic effector cells. Further studies are required to explore whether these changes are generated by mutational events correlated with TZC-induced CX of human cancer cells. PMID- 1917442 TI - RBRVS: still good news for physicians. AB - Lately, many physicians have been saying they've become disillusioned with the RBRVS. They don't believe the physician payment reform will bring gains for their undervalued evaluation and management services. They don't trust the federal government to live up to its end of the bargain. However, no one should write off the RBRVS. As can be seen from the text below, RBRVS will protect undervalued evaluation and management services in an era of medicare budget-cutting; it will introduce fairness and rationality into the Medicare payment system; it will provide a basis for arguing against unfair cuts in reimbursement (such as the recent ban on payment for most EKG interpretations) and it will bring the profession together to fight against any further cuts in the Medicare program. PMID- 1917443 TI - The friends of the medical school. AB - The Friends of the John A. Burns School of Medicine, as an organization, is an extension of a basic need. Mary Cutting has compiled a history of the organization in which she was an instrumental force. Some of the highlights are included below. PMID- 1917444 TI - Alcohol and sleep apnea. AB - Acute ingestion of ethanol induces vasodilation and swelling of respiratory mucosa; it depresses respiratory centers resulting in hypotonia of oropharyngeal dilator muscles and inducing or aggravating sleep apnea. However, no association between the sleep apnea syndrome (SAS) and Alcohol Use Disorders (AUD) has been demonstrated. PMID- 1917445 TI - Monoclonal antibodies. PMID- 1917446 TI - The origins of the government's doctors in Scotland. PMID- 1917447 TI - 50 years of Health Bulletin: a reminiscent retrospect. PMID- 1917448 TI - Scottish sport to the year 2000--its impact on health. PMID- 1917449 TI - Continuing hospital care in Scotland: a survey of consultant geriatricians. AB - We report a survey of Consultant Geriatricians in Scotland with regard to the provision of continuing geriatric care. There are wide variations in the numbers of patients that individual consultants are responsible for, the type and geographical site on which a service is provided, and also in views on the adequacy of staffing levels. Quality of physical surroundings and nursing care are generally thought to be more than adequate. Consultants believed their main contribution was providing expert medical advice, and felt their patients' quality of life could most be improved by increased diversional therapy. There are wide geographical differences in the number of private nursing and residential homes in Scotland but they have had some influence on the criteria for placement of patients in continuing hospital care. PMID- 1917450 TI - An assessment of computing activity by GPASS users in Scottish general practice. AB - The electronic questionnaire has been developed as a means of collecting data held on computers in Scottish General Practices using the standard national general practice computer system (GPASS). In 1989, data were gathered from 251 computerised Scottish practices using a floppy disc based interrogation program, amalgamated and then analysed. The results of this study are presented and examined in three separate ways: by region, by date of initial computerisation, and by list size per general practitioner (GP). PMID- 1917452 TI - Euthanasia 1990--attitudes in Britain, USA and The Netherlands. PMID- 1917451 TI - Public knowledge of hospices: a street survey in Glasgow. AB - A street survey was conducted in Glasgow to find out the level of public knowledge of and attitudes to hospices generally and two local hospices. The level of knowledge was not high, though attitudes to hospices were positive. Those few respondents with unfavourable attitudes had little knowledge of hospices generally and knew little about the local hospices. The factors associated with level of knowledge and attitudes were different for the two local hospices. The media and the collection of money for hospices were the main source of knowledge. PMID- 1917454 TI - Music therapy in Scotland: an introduction. PMID- 1917453 TI - Cervical cancer screening: women's knowledge, attitudes and preferences. AB - Screening status of women aged 20-64 registered with a large group practice was determined using laboratory and general practice records. A postal survey was carried out on 1,416 women divided into: 1. 'Non-attenders'--never had a smear. 2. 'Defaulters'--smear more than five years ago. 3. 'Attenders'--smear in last five years. Screening status was related to social class and education. Single and nulliparous women were less likely to have been screened. Knowledge of the test was poor in all three groups. Most women were willing to have a smear performed and previous non-attendance might have been overcome by a call/recall system. The woman's general practitioner was the preferred taker of smears, regardless of sex. Of those willing to have the test 95% would attend the general practitioner if no alternative was provided. Improved uptake depends on an organised call/recall system with smear taking based in primary care, and on improved health education. PMID- 1917455 TI - Music therapy--a review. PMID- 1917456 TI - The Scottish Dentists' Questionnaire 1987: an overview. PMID- 1917457 TI - [Sexual transmission of hepatitis viruses]. PMID- 1917458 TI - [Borrelia infections of the skin--progress of knowledge since the discovery of Lyme disease]. AB - The description of Lyme disease in 1976 and the detection of its causative agent, the spirochete Borrelia burgdorferi (B. burgdorferi), in 1982 led to an increase in our knowledge of the course of B. burgdorferi infection and its clinical manifestations. The classic tick-borne dermatoses erythema chronicum migrans (ECM), lymphadenosis benigna cutis (LABC) and acrodermatitis chronica atrophicans (ACA) were proven by isolation of the spirochete from skin lesions to be caused by B. burgdorferi infection. In early disease (less than 1 year) ECM and LABC can develop locally at the site of infection (stage I), but both these skin manifestations can also occur together with multiple lesions after dissemination of the causative organism (stage II). ACA is typical for late infection (greater than 1 year, stage III). High titres of B. burgdorferi antibodies have been found in patients with localized sclerodermalike lesions (circumscribed scleroderma, lichen sclerosus et atrophicus, anetoderma), and frequent simultaneous occurrence of ACA suggests an association with late B. burgdorferi infection. Similarly, we found four cases of cutaneous B-cell lymphoma possibly arising from LABC in association with the same markers of late B. burgdorferi infection. Additionally, some cases of Schonlein-Henoch purpura and of Shulman syndrome may be associated with Lyme borreliosis. The disease is endemic in central Europe, and almost exclusively ticks of the Ixodes ricinus complex seem to transmit B. burgdorferi to humans, whereas the reservoir of infection seem to be rodents, especially mice. The main diagnostic tool is serological examination for B. burgdorferi antibodies, which will become detectable 3-6 weeks after infection. Enzyme-linked immunosorbent assay (ELISA) and the indirect immunofluorescence test (IFT) revealed similar sensitivity. In early disease, sensitivity for antibody detection could be improved by immunoblot technique and by flagellum-ELISA, which is specific for this early sensitizing B. burgdorferi antigen. For treatments, penicillin is no longer recommended as the drug of first choice, because low sensitivity of B. burgdorferi has been observed in vitro and in vivo. Tetracycline, doxycycline and amoxicillin p.o. are now preferred for the treatment of Lyme borreliosis, and in neurologic and cardiac abnormalities ceftriaxone i.v. is recommended. Treatment duration should be 14 days in early disease and 30 days in late disease. PMID- 1917459 TI - [Epidemiology of urticaria diseases]. AB - In a prospective analysis, all patients presenting with urticaria in the practices of a general practitioner and a dermatologist and at a university clinic in the course of a year were ascertained and underwent diagnostic examination according to a uniform scheme. Urticarias are common skin diseases, affecting, at a modest estimate, about 1.3% of the population. Of all the general practitioner's patients about 3% had one of the many types of urticaria. The same percentage was found in the dermatologist's practice and among the patients attending the university clinic. The incidence of the different types of urticaria differs considerably at the different levels of medical care. This may be due to the fact that the patients are referred to a specialist or to a clinic only when the diagnosis or treatment is problematic. Half the general practitioner's urticaria patients suffer from physical urticarias (this includes the minor variants that do not necessarily require medical care). In the clinic, however, only a quarter of all patients with urticaria had physical variants. Patients with chronic urticaria accumulate in clinics because they have been referred for diagnosis and therapy. Predominantly young people were affected by physical urticaria, the peak being between 10 and 40 years. Patients with chronic "endogenous" urticaria were significantly older. About 30% of all patients also had angio-oedema, at least temporarily. Isolated swelling without urticaria occurred in only 3.9% of all patients. In urticaria, there was a slight female predominance: of all patients with physical urticaria, 61.1% were female, and the corresponding figure for nonphysical types was 53.6%. An almost equal sex distribution was found in chronic urticaria (51.9% female). In our prospective study patients presenting with urticaria only as a minor symptom was also ascertained. Many minor variants of physical urticaria were seen in these patients. In the dermatological practice, urticaria was diagnosed incidentally in 6-8% of cases. In the clinic, however, 20% of the physical urticarias and 10% of the acute nonphysical urticarias were recorded as incidental findings. PMID- 1917460 TI - [Computer networks in clinical practice--a histology data bank system]. AB - In hospital and in private practice huge amounts of data have to be managed. Conventional storage and documentation techniques are being replaced more and more by the use of computers. Local area networks based on the interconnection of stand-alone PC workstations offer several advantages over non-communicating systems. The use of computer networks solves many communication problems and in this way improves the flow of information. The interconnection may be achieved by step-by-step integration of preexisting elements. This paper presents a database system for archiving routine histology data and illustrates the use of a computer network in a dermatology department. PMID- 1917461 TI - [Therapy of progressive scleroderma with gamma-interferon]. AB - In an open study conducted over 6 months, gamma interferon was administered to 12 patients suffering from progressive systemic sclerosis. The dosage used was three injections, each of 50 micrograms s.c. in the first 2 weeks, followed by 50 micrograms twice a week. All patients fulfilled the criteria required for classification as type II in the ADF system or the major criterion of the ARA (proximal sclerosis). Therapeutic effects were noted as a decrease in of skin thickness (10/12 = 83%), improvement in muscle and joint pains (5/8 = 63%) and reduction of the procollagen-type III peptide in serum by more than 20% (8/12 = 66%). No effects on fibrosis or dysfunction of internal organs were seen. Disease progression did not occur in any of the patients. Side-effects of gamma interferon were noted in 4 patients, in the form of slightly elevated body temperature and transient influenza-like symptoms, but these occurred only at the beginning of therapy and soon passed. PMID- 1917462 TI - [Systemic proliferative angioendotheliomatosis: a cutaneous manifestation of malignant B-cell lymphomas. Histologic and immunohistologic studies of two cases]. AB - Angioendotheliomatosis proliferans systemisata (AEPS) is a rare disease entity characterized by a predominantly intravascular proliferation of tumour cells. Two forms of AEPS are differentiated: a very rare, benign and self-limiting form, which is endothelial in origin, and a more common, malignant form, which is an angiotropic intravascular malignant B-cell lymphoma. Histological and immunohistological investigations of the malignant form of AEPS are presented: In a 69-year-old woman cutaneous lesions appeared 5 months before the diagnosis of B immunoblastic lymphoma. In a 57-year-old woman lesions were observed simultaneously with the relapse of a high-grade malignant B-cell lymphoma. Immunohistological identification of the proliferating cell type made diagnosis of intravascular B-cell lymphoma possible in paraffin-embedded biopsies. PMID- 1917463 TI - [Systemic treatment of common warts with beta-interferon]. AB - A 21-year-old female suffering from recalcitrant subungual and periungual common warts was treated without success for 3 years by both conservative and surgical approaches. After intravenous therapy with human fibroblast beta interferon (IFN beta; 3 cycles, 14 days each; daily dose 1-3 x 10(6) IU) complete remission of all warts was achieved. Even 1 year after the treatment with human IFN-beta, the patient was still free of warts. We conclude that in selected cases common warts can be treated with intravenous human fibroblast IFN-beta. However, because of the high cost of this well-tolerated therapy, it cannot be recommended for all patients with common warts. PMID- 1917464 TI - [Mineral salts for support in selective ultraviolet phototherapy]. PMID- 1917465 TI - [History of the foundation of the German Society of Dermatology]. PMID- 1917466 TI - [Dermatologic phototherapy]. PMID- 1917467 TI - [Polymerase chain reaction--principle and application in medicine]. AB - The polymerase chain reaction, a new molecular technique, is of increasing importance in many areas of medical research and diagnosis. Within hours DNA sequences can be amplified millionfold with very high specificity, making detection and further analysis possible. Using multiple rounds of exponential amplification, even one copy of a gene of interest can be detected by agarose gel electrophoresis and other methods. Furthermore, minute amounts of DNA even from tissue damaged by embedding in paraffin can be analysed. Polymerase chain reaction methodology has already gained significance in many areas of medical research, e.g. diagnosis of inherited diseases, detection of viral DNA in clinical samples, cancer research and diagnosis, and characterization of gene expression. PMID- 1917468 TI - [Lipedema]. AB - An overall view of the clinical findings in lipedema is given and of its treatment. Lipedema is shown to be a distinct illness, and not just a disturbance of the distribution pattern of subcutaneous fatty tissue. The diagnosis is based on an accurate history and specific criteria on clinical examination and palpation. PMID- 1917469 TI - [Oral hairy leukoplakia in patients with kidney transplantation]. AB - Oral hairy leukoplakia was initially reported only in HIV-infected patients and was considered pathognomonic for HIV infection. The presence of Epstein-Barr virus and the decrease in Langerhans cells seem to be necessary for the development of oral hairy leukoplakia. HIV antigen is not present in oral hairy leukoplakia. We report on seven renal transplant recipients with oral hairy leukoplakia. In six of these patients no HIV infection was present. All patients showed marked immunosuppression following a vigorous immunosuppressive regimen. Five patients each had several rejection episodes, which were treated with further immunosuppressive therapy in addition to the basic immunosuppressive regimen. One patient was infected with HIV from the renal graft and another suffered from liver cirrhosis with portal hypertension caused by chronic hepatitis B infection. We believe that oral hairy leukoplakia is a marker for severe immunosuppression that is not necessarily associated with HIV infection. Organ transplant recipients undergoing dermatological check-up should be examined for oral hairy leukoplakia. PMID- 1917470 TI - [Structure analysis of the skin surface using computer-assisted laser profilometry. New method for the quantitative assessment of roughness structure of the skin]. AB - Up to now, it has been difficult to record the roughness of the skin and to define it satisfactorily by measuring techniques. A new method for computer assisted structural analysis of the skin surface is introduced, which uses laser beams for measurement without contact. This measuring technique is suitable for quantitative characterization of normal skin surfaces and for pathological alterations to the skin surface. Because of the dynamic properties of the skin, it is characterized by means of silicone replicas of the skin surface. Different parameters of roughness are determined and completed by mathematical and statistical processes such as Fourier transform and an autocorrelation function. These processes are related to the digitally stored three-dimensional profile of the skin surface. The new method is presented by means of some examples characterizing a typical clinical finding of rough eczematous skin. A comparison with photographs taken with a scanning electron microscope demonstrates the quality of resolution achieved with the measuring technique. PMID- 1917471 TI - [Acute disseminated histiocytosis X (Langerhans cell histiocytosis) with fatal course in an adult]. AB - Histiocytosis X is very rare in late adulthood, usually taking a benign course with a good prognosis. A 56-year-old patient developed acute disseminated histiocytosis X with multiorgan involvement. Despite extensive diagnostic work-up the diagnosis could only be established on the grounds of a skin biopsy. Histiocytosis X cells are S 100 protein-positive and express the membrane antigens CD 1, CD 4 and HLA-DR. Electron microscopy reveals Birbeck granules. On static cytophotometry, histiocytosis X cells exhibited normal DNS content without aneuploidy. One year after the onset of disease the patient's condition deteriorated rapidly despite aggressive polychemotherapy (CHOP), and he died of multiorgan failure due to histiocytosis X. PMID- 1917472 TI - [Laugier-Hunziker-Baran syndrome]. AB - Laugier-Hunziger-Baran syndrome is characterized by lenticular melanin pigmentation of the lips and oral mucosa that may be associated with longitudinal melanonychia. Neither a systemic nor a local cause is demonstrable. There is no risk of development of oral or subungual malignant melanoma. Fifteen cases of this syndrome, which has not yet been reported in the German literature, are described. PMID- 1917473 TI - [Cheilitis et pareitis granulosa: spontaneous course]. AB - Our report describes the spontaneous development of a cheilitis granulomatosa of a 50 year old female patient. In the course of the disease spontaneous regression alternated with pareitis granulomatosa. PMID- 1917474 TI - [Tumor form of lymphostatic papillomatosis of the skin]. AB - The case of a patient with two plantar papillomatous tumours that had had a relapsing course over 10 years is presented. The tumours were located on the right forefoot and the left great toe. Several operations were performed for different diagnoses, i.e. plantar verrucae, verrucous carcinoma and pyoderma vegetans. Histologically, the papillomas proved to be pseudocarcinomatous hyperplasias with multiple ectatic dermal lymph plexuses. Indirect lymphography revealed a circumscribed lymphatic dysplasia with cystic-ectatic cutaneous vessels within the tumour area. Draining lymphatic collectors were conspicuously reduced in number. Isotope lymphography showed a normal lymph transport rate from the foot to the groin. It is concluded that the circumscribed disturbance of lymphatic drainage is the decisive cause of the reactive papillomatous hyperplasia. Thus, these papillomas clinically resembling verrucous carcinoma represent the tumour variant of a papillomatosis cutis lymphostatica. PMID- 1917475 TI - [Eosinophilic cellulitis--clinical and histological aspects]. AB - Eosinophilic cellulitis (Wells' syndrome) is a rare skin disease whose aetiology is still unknown. The onset is acute, and different disease stages may exist simultaneously during the course. Histological examination shows flame figures as a characteristic, but not pathognomonic, feature. In later stages the infiltrate adopts granulomatous characteristics. Malignant haematological disorders, which frequently occur with this disease, should be excluded. PMID- 1917476 TI - [Skin manifestations in myopathies]. PMID- 1917477 TI - [The treatment of pressure urticaria with anti-inflammatory agents]. PMID- 1917478 TI - [Memorandum and recommendations by the German Society for Andrology and the German Society for the Study of Fertility and Sterility on the status of andrology in the Federal Republic]. PMID- 1917479 TI - 1991 Distinguished Scientific Achievement Award presented to William J Bair. PMID- 1917480 TI - 1991 Founders Award presented to Melvin W. Carter. PMID- 1917481 TI - 1991 Elda E. Anderson Award presented to James E. Tarpinian. PMID- 1917482 TI - 1991 William McAdams Outstanding Service Award. PMID- 1917484 TI - Evaluation of ocular hazards due to electric arc flash at an in-line switch. AB - We investigated the ocular damage resulting from operation of a solid blade pole mounted in-line electrical switch at between 16 and 17 kV with current loads between 38 A and 340 A. Spectroradiometric data for the electric arcs produced as the switch was opened were obtained over the waveband 200 to 1500 nm. The eyes of adult pigmented rabbits were exposed to the arc flash at a distance of 2 m. The ocular tissues were assessed clinically and histologically up to 48 h postexposure. Threshold damage was clinically detectable only in eyes exposed to a 340 A arc. We conclude that at the normal current loads on a 17-kV electric power transmission line, the principal oculovisual hazards are due to molten metal fulminated from the switch by the arc, and after-images due to the bright visible light flash. At a working distance of 2 m, the ultraviolet ocular hazard is negligible. Adequate eye protection is provided by clear polycarbonate safety lenses. PMID- 1917483 TI - Calculation of shielding door thicknesses for radiation therapy facilities using the ITS Monte Carlo program. AB - Shielding calculations for door thicknesses for megavoltage radiotherapy facilities with mazes are generally straightforward. To simplify the calculations, the standard formalism adopts several approximations relating to the average beam path, scattering coefficients, and the mean energy of the spectrum of scattered radiation. To test the accuracy of these calculations, the Monte Carlo program, ITS, was applied to this problem by determining the dose and energy spectrum of the radiation at the door for 4- and 10-MV bremsstrahlung beams incident on a phantom at isocenter. This was performed for mazes, one termed "standard" and the other a shorter maze where the primary beam is incident on the wall adjacent to the door. The peak of the photon-energy spectrum at the door was found to be the same for both types of maze, independent of primary beam energy, and also, in the case of the conventional maze, of the primary beam orientation. The spectrum was harder for the short maze and for 10 MV vs. 4 MV. The thickness of the lead door for a short maze configuration was 1.5 cm for 10 MV and 1.2 cm for 4 MV vs. approximately less than 1 mm for a conventional maze. For the conventional maze, the Monte Carlo calculation predicts the dose at the door to be lower than given by NCRP 49 and NCRP 51 by about a factor of 2 at 4 MV but to be the same at 10 MV. For the short maze, the Monte Carlo predicts the dose to be a factor of 3 lower for 4 MV and about a factor of 1.5 lower for 10 MV. Experimental results support the Monte Carlo findings for the short maze. PMID- 1917485 TI - Mobility and plant uptake of inorganic 14C and 14C-labelled PCB in soils of high and low retention. AB - Quantifying and understanding the mobility of 14C and organic pollutants in soils is important, especially in the context of underground waste disposal. We studied migration of 14C applied as NaHCO3 (14C-CO3) and as 2,2',5,5' tetrachlorobiphenyl (14C-PCB) in carbonated, high-organic-matter-content and acidic, low-organic matter-content undisturbed soil cores. The mobility of 14C-PCB depends on the profile distribution and amount of soil organic matter, whereas the mobility of 14C-CO3 depends primarily on the soil carbonate content. The solid/liquid partition coefficients (Kd) for 14C-CO3 were 6.7 and 1.2 mL g-1 for the two soils, respectively. For the 14C-PCB, the corresponding Kd values were 49 and 22 mL g-1. Plant/soil concentration ratios (CR) for inorganic 14C have previously been derived using overly conservative assumptions. Using plants grown in outdoor lysimeters, CR values for 14C-CP3 of 0.7 and 1.3, on a dry-weight basis, were measured for the two soils. These values are about 25-fold lower than the currently used values. The corresponding CR values for 14C-PCB were 0.014 and 0.088. For both 14C sources, there was evidence of atmospheric transfer from the soil to the plants. This was especially important for 14C-CO3, where it may have been dominant. Detailed modelling of 14C transport from underground waste disposal should include volatilization as a loss process from soil as well as a source for plants. PMID- 1917486 TI - Recognition of microclimate zones through radon mapping, Lechuguilla Cave, Carlsbad Caverns National Park, New Mexico. AB - Radon concentrations range from less than 185 to 3,515 Bq m-3 throughout Lechuguilla Cave, Carlsbad Caverns National Park, New Mexico. Concentrations in the entrance passages and areas immediately adjacent to these passages are controlled by outside air temperature and barometric pressure, similar to other Type 2 caves. Most of the cave is developed in three geographic branches beneath the entrance passages; these areas maintain Rn levels independent of surface effects, an indication that Rn levels in deep, complex caves or mines cannot be simply estimated by outside atmospheric parameters. These deeper, more isolated areas are subject to convective ventilation driven by temperature differences along the 477-m vertical extent of the cave. Radon concentrations are used to delineate six microclimate zones (air circulation cells) throughout the cave in conjunction with observed airflow data. Suspected surface connections contribute fresh air to remote cave areas demonstrated by anomalous Rn lows surrounded by higher values, the presence of mammalian skeletal remains, CO2 concentrations and temperatures lower than the cave mean, and associated surficial karst features. PMID- 1917487 TI - Determining the 222Rn exhalation rate of building materials using liquid scintillation counting. AB - A new method for determining the free 222Rn exhalation rate from building materials is described. The sample is enclosed in a container from which the exhaled Rn is continuously purged by nitrogen gas. After 2-3 h, when the Rn level in the container has reached a steady-state concentration, the outflowing Rn is trapped on silica gel at about -190 degrees C. About 16 h after sampling, the silica gel is analyzed by liquid scintillation counting to determine the area exhalation rate. The method described has a good repeatability and reproducibility with coefficients of variation of 7.8% and 8.3%, respectively, at 5 Bq m-2 h-1. The low limit of detection of 11 mBq 222Rn offers the opportunity to quantify the exhalation rate of almost all kinds of building materials. It was found that the air humidity strongly influences the exhalation rates of building material and, therefore, should be controlled. Two typical building materials were investigated. For gypsum, an increase in the exhalation rate with increasing water vapor pressure was found, whereas for concrete, a linear decrease with increasing water vapor pressure was observed. The 222Rn area exhalation rates of 20 Dutch building materials, including some experimental ones, were determined at 50% RH, 20 degrees C, showing a range of less than 0.02-15.8 Bq m-2 h-1. The lowest values were found for natural gypsum board, the highest for phosphogypsum blocks. Building materials containing fly ash gave area exhalation rates comparable to those of similar materials without fly ash. PMID- 1917488 TI - Half-lives of 214Pb and 214Bi. AB - New measurements on chemically separated samples of 214Bi have yielded a mean half-life value of 19.71 +/- 0.02 min, where the error quoted is twice the standard deviation of the mean based on 23 decay runs. This result provides strong support for the historic 19.72 +/- 0.04 min half-life value and essentially excludes the 19.9-min value, both reported in previous studies. New measurements of the decay rate of 222Rn progeny activity initially in radioactive equilibrium have yielded a value of 26.89 +/- 0.03 min for the half-life of 214Pb, where the error quoted is twice the standard deviation of the mean based on 12 decay runs. This value is 0.1 min longer than the currently accepted 214Pb half-value of 26.8 min. PMID- 1917489 TI - Perspective on the historical development of radiation standards. AB - This paper discusses the historical development of standards for limiting routine radiation exposures of workers and the public. The radiobiological and epidemiological basis for radiation protection standards and practices, as this basis has evolved over time, is emphasized. Difficulties with using dose equivalents and nominal risk factors, which were developed primarily for purposes of radiation protection (i.e., to establish dose limits), in estimating radiation risks at the low levels of exposure routinely experienced in the workplace and the environment are discussed. The increasing importance of the principle that exposures should be reduced as low as reasonably achievable (ALARA) in radiation protection of workers and the public is described. PMID- 1917490 TI - Use of thin thermoluminescent dosimeters for phantom surface-dose measurements. PMID- 1917491 TI - Short- vs. long-term indoor radon measurements. AB - The major advantage of short-term vs. long-term indoor Rn measurements is that the information is available rapidly. A study of the results obtained for Rn measurements developed in Spain, employing grab samples and 3-mo alpha-track measurements, is discussed. PMID- 1917493 TI - A local area network for controlling the ordering and purchasing of radioactive material. AB - Efficient control over the purchase and receipt of radioactive material is a necessary part of any radiation safety program. We describe a novel computerized method for monitoring the flow of radioactive material within a large broad licensed medical research complex. The Local Area Network (LAN) described interfaces the radiation safety office with radionuclide receiving, the authorized user, grants and contracts, special accounts, and purchasing. Task specific software enables the authorized user to place an order and allows the monitoring of possession/ordering limits, personnel, date of order, and time of receipt via the screen. The resultant data base is easily annexed for specific information. The system is user-friendly and adaptable to any set of circumstances. PMID- 1917492 TI - The measurement system for 222Rn monitoring with charcoal adsorption collectors. PMID- 1917494 TI - A description of the demonstration Integral Fast Reactor fuel cycle facility. AB - A fuel examination facility at the Idaho National Engineering Laboratory is being converted into a facility that will electrochemically process spent fuel. This is an important step in the demonstration of the Integral Fast Reactor concept being developed by Argonne National Laboratory. Renovations are designed to bring the facility up to current health and safety and environmental standards and to support its new mission. Improvements include the addition of high-reliability earthquake hardened off-gas and electrical power systems, the upgrading of radiological instrumentation, and the incorporation of advances in contamination control. A major task is the construction of a new equipment repair and decontamination facility in the basement of the building to support operations. PMID- 1917495 TI - Radiation shielding design for a hot repair facility. AB - A new repair and decontamination area is being built to support operations at the demonstration fuel cycle facility for the Integral Fast Reactor program at Argonne National Laboratory's site at the Idaho National Engineering Laboratory. Provisions are made for remote, glove wall, and contact maintenance on equipment removed from hot cells where spent fuel will be electrochemically processed and recycled to the Experimental Breeder Reactor-II. The source for the shielding design is contamination from a mix of fission and activation products present on items removed from the hot cells. The repair facility also serves as a transfer path for radioactive waste produced by processing operations. Radiation shields are designed to limit dose rates to no more than 5 microSv h-1 (0.5 mrem h-1) in normally occupied areas. Point kernel calculations with buildup factors have been used to design the shielding and to position radiation monitors within the area. PMID- 1917496 TI - Response to Scarpitta and Harley's 'Radon calibration factor for charcoal canisters'. PMID- 1917497 TI - Human subjects used for biokinetic studies. PMID- 1917498 TI - Ad hominem commentaries do not belong in scientific journals. PMID- 1917499 TI - Interhospital variations in admission severity-adjusted hospital mortality and morbidity. AB - In this study hospital admissions are categorized into admission severity groups based on key clinical findings. Severity of illness is determined again later in the hospital stay after treatment has been initiated. High severity on this second review is labeled major morbidity or morbidity, depending on the severity level, and these rates serve as a health outcome indicator along with in-hospital mortality. This study's findings show, for ten hospitals randomly selected from MedisGroups users, considerable interhospital variation in standardized mortality and morbidity ratios for ten frequently occurring DRGs on the adult medical service. After adjusting for admission severity and case mix, three of the ten study hospitals have a statistically significant (p less than .01) difference between the hospital's standardized mortality ratio and 1.0. Such a significant difference exists for the standardized major morbidity ratio of four hospitals and for the standardized morbidity ratio of three hospitals. At the DRG-specific level, our results show that 8.9 percent, 4.4 percent, and 15.0 percent of the hospital-specific mortality, major morbidity, and morbidity ratios, respectively, are statistically significant. Most hospital outliers have fewer deaths or morbid cases than expected. We caution that the study hospitals may not be representative of a larger group of U.S. hospitals. PMID- 1917500 TI - Measuring outcomes of hospital care using multiple risk-adjusted indexes. AB - Using existing data sources, we developed three risk-adjusted measures of hospital quality: the risk-adjusted mortality index (RAMI), the risk-adjusted readmissions index (RARI), and the risk-adjusted complication index (RACI). We describe the construction and validation of each of these indexes. After these measures were developed, we tested the relationships among the three indexes using a sample of 300 hospitals. Actual numbers of adverse events were observed for each hospital and compared to the number predicted by the RAMI, RARI, and RACI models. Then each hospital was ranked on each index. Our results showed that no relationship existed between a hospital's ranking on any one of these indexes and its ranking on the other two indexes. This result provides some evidence that no measure of quality should be used by itself to represent different aspects of the quality of hospital care. Adequate overall measures of hospital quality will need to include multiple measures in order to be credible and to reflect the complexity of hospital care. The findings suggest that consumers, payers, and policymakers cannot simply choose one hospitalwide measure, such as the mortality rate, to validly represent a hospital's performance: those hospitals with high rankings on their mortality rates do not necessarily rank high on their readmission rates or complication rates. PMID- 1917501 TI - AIDS case management: the client's perspective. AB - The Robert Wood Johnson Foundation's AIDS Health Services Program uses case management to provide community-based care for people with AIDS. This article reports data concerning implementation of case management, based on interviews with program clients in nine communities. Some clients receive case management from a community-based organization (CBO), while others have clinic-based case managers. Clinic clients are more likely to be disadvantaged. Over 25 percent of respondents report having no case manager at either site, and 10 percent report having two case managers. Those who need social services are more likely to have a case manager. Between 18 and 25 percent have had no contact with their case manager in a month, but over 50 percent have had multiple contacts. Frequency of contact is positively related to having needs for social services. Evaluations of case managers are favorable, but there is some dissatisfaction with ease of access. Having a case manager is positively related to having service needs met. Results suggest that (1) efforts to coordinate care through case management must deal with the existence of clinics and CBOs as distinct treatment sites with differing clientele, and (2) explicit policies concerning eligibility for case management and frequency of monitoring must be developed. PMID- 1917502 TI - Case management: a randomized controlled study comparing a neighborhood team and a centralized individual model. AB - This randomized controlled study compared two types of case management for skilled nursing level patients living at home: the centralized individual model and the neighborhood team model. The team model differed from the individual model in that team case managers performed client assessments, care planning, some direct services, and reassessments; they also had much smaller caseloads and were assigned a specific catchment area. While patients in both groups incurred very high estimated health services costs, the average annual cost during 1983-85 for team cases was 13.6 percent less than that of individual model cases. While the team cases were 18.3 percent less expensive among "old" patients (patients who entered the study from the existing ACCESS caseload), they were only 2.7 percent less costly among "new" cases. The lower costs were due to reductions in hospital days and home care. Team cases averaged 26 percent fewer hospital days per year and 17 percent fewer home health aide hours. Nursing home use was 48 percent higher for the team group than for the individual model group. Mortality was almost exactly the same for both groups during the first year (about 30 percent), but was lower for team patients during the second year (11 percent as compared to 16 percent). Probable mechanisms for the observed results are discussed. PMID- 1917503 TI - Medicaid beneficiaries under managed care: provider choice and satisfaction. AB - This study describes patterns of choosing a provider and of consumer satisfaction among prepaid Medicaid beneficiaries in Monroe County, New York, and compares their level of satisfaction to that of fee-for-service Medicaid beneficiaries. Two interview surveys were conducted with AFDC and HR (general assistance) Medicaid eligibles, the first under the fee-for-service system servicing the Medicaid population, and the second 18 months after the introduction of a mandatory, prepaid managed care system for Medicaid beneficiaries. The results show significant ethnic differences in patient choice of provider and provider site. Given the choice, Medicaid beneficiaries switch from clinics as their usual source of care to private physician practice. Under prepayment, white Medicaid beneficiaries tripled their affiliations with private doctors, while "others" doubled theirs. The results also demonstrate higher levels of patient satisfaction with "humaneness of doctors" and with "quality of care" among those beneficiaries under prepaid care, than previously documented for those under fee for-service. The evaluations of humaneness and quality of medical system may reflect the respondents' perceptions that the process of receiving care under prepaid, managed care is somehow different, no longer second class, and better that it was under the fee-for-service Medicaid. PMID- 1917505 TI - Critical thinking for environmental health risk education. AB - This article proposes an approach for helping school-age children to think critically about environmental health risks. It discusses three key elements of a school curriculum--defining a decision perspective, making choices under uncertainty, and thinking about consequences--and recommends procedures to aid in classroom implementation of the proposed ideas. Critical thinking skills are shown to enhance childrens' ability to anticipate the health or safety consequences of a decision by distinguishing automatic from decision thinking, by detecting inconsistent objectives or neglected consequences, and by making explicit value-based tradeoffs. Training in critical thinking also should empower children because it acknowledges the power of personal initiatives in decreasing health risks and, in general, because it focuses the classroom experience on learning about how to think rather than merely learning about what to think. PMID- 1917504 TI - Relationship between patient race and survival following admission to intensive care among patients of primary care physicians. AB - This study investigated the existence of racial differences in the survival of patients admitted to intensive care by family physicians and general internists for circulatory illnesses. The study population consisted of 249 consecutive patients admitted by these specialists to an ICU in a tertiary care hospital in Pitt County, North Carolina, during the June 1985 to June 1986 period. Logistic regression was used to specify the unique effect of race on ICU patient survival in-hospital, controlling for potential confounding factors such as disease severity, type of health insurance, and case mix. Black patients were almost three times more likely than white patients to die in-hospital following admission to the ICU (RR = 2.9, 95 percent I = 1.5, 5.6). Most of this difference in survival was explained by racial differences in disease severity. PMID- 1917506 TI - Predictors of risk perceptions of childhood injury among parents of preschoolers. AB - This article assesses the relationship between parents' perceived risk of childhood injuries and familial, sociocultural, and situational variables. Data were obtained through a random digit dial telephone survey of 1,200 households with a preschool child in a southeastern metropolitan area. Perceived risks of childhood injury measures were based on social science theory and childhood injury epidemiology. Multiple item measures included dimensions of seriousness and likelihood for both injuries and hazards. When risk perceptions were viewed as individual items, parents underestimated the risk of some hazards and injuries and overestimated the risks of others, and parents whose children have sustained a recent injury had higher risk perception overall. When risk perceptions were viewed as summed scales, sociodemographic variables and parental safety behaviors were not significant predictors. Sociocultural factors of having a child previously injured, the parent reporting stress, having a household with self reported risk factors, and the perception of the child as active and hard to manage are related to summed scales of risk perceptions, with some interactions by race of the parent. Findings illustrate the role of situational and sociocultural characteristics of respondents in risk perception research. PMID- 1917507 TI - Communicating with environmental and health risk takers: an individual differences perspective. AB - This research explores the effects of different messages strategies in interaction with individual differences in risk taking. The data are from two field experiments (2 x 2 x 3 factorial design) with 506 adults. The message variables are risk targets, media formats, and information sources. Results indicate individual differences in concern and information seeking for Adventurous, Impulsive, and Rebellious risk takers. Rebellious risk taking is negatively associated with information seeking and impulsive risk taking is negatively associated with both concern, and information seeking. For the rebellious risk taker, a newspaper article with a state agency source caused higher levels of concern and information seeking about the risk than a newspaper article with the Surgeon General as the source. In contrast, for the impulsive risk taker, concern about the risk is greatest when the message is from a state agency source and in a brochure. What is a successful source and media strategy with one type of risk taker may have no effects or even negative effects with another type of risk taker. PMID- 1917508 TI - The relationship between radon knowledge, concern and behavior, and health values, health locus of control and preventive health behaviors. AB - Understanding similarities between health-related and radon-related knowledge, attitudes, and behaviors may suggest application of effective strategies of radon related education in targeted populations. A mail survey was returned by 300 randomly selected homeowners in a community at risk for high home radon concentrations (50% response). While 64% were concerned, only 7% tested their homes. The expected association between radon knowledge, radon concern, and information-seeking was identified. In addition, those who tested their homes had greater knowledge and did more information seeking. Health values and radon concern were only weakly related. Environmental concern explained the greatest variance in radon concern (10%). Internal health locus of controls were more likely to have high radon concern. Of the preventive health behaviors, not smoking and seat belt use were the best predictors of variance in radon concern (5%). Segmenting the population is suggested for best educational outcome. Relating information to environmental issues may be helpful. Health-conscious people may need awareness of risks. Issues of self-control and radon testing and reduction may be helpful for some. Synergy between smoke and radon, compounded by smokers lack of concern suggests targeting smokers for education efforts. PMID- 1917509 TI - Healthy cities: the Indiana model of community development in public health. AB - While the Institute of Medicine's Report on The Future of Public Health provokes debate on public health issues in the United States, the Healthy Cities movement is one approach to addressing many of these issues. Healthy Cities Indiana began in 1988 and adapts the European and Canadian healthy cities experience within the sociopolitical context of Indiana and the United States. Six Indiana cities are collaborating with Indiana University School of Nursing and the Indiana Public Health Association in a process of urban health promotion. The overall healthy cities process is presented including: city commitment, formation of healthy city committee, community leadership development, city action, provision of data-based information to policy makers, and action research and evaluation. Each step in the healthy cities process is described, highlighting examples from the Indiana experience, including an analysis of selected data describing the cities. The facilitators of a healthy city provide support to city leaders in other cities interested in becoming involved in the healthy cities process. Implications of healthy cities for health educators and other health professionals are suggested. PMID- 1917510 TI - Communicating about environmental risks: how the public uses and perceives information sources. PMID- 1917511 TI - Newspaper coverage of cancer clusters. AB - This study reports an analysis of 176 newspaper articles about cancer clusters. The type of diseases, number of diseases, and status of ongoing health investigations were reported in the majority of articles. But background information such as, comparison of actual and expected number of cases, environmental causes and their confounders, and the existence of other clusters were not reported as often. Statements about risk were reported in most articles and, contrary to our expectations, were relatively balanced among risk asserting, risk denying, and mixed opinions. We noted a preponderance of risk asserting statements in the beginning of stories. Cluster stories cited an average of three sources, and two of these three sources were usually government officials. The remaining sources were divided among citizens, representatives of environmental advocacy groups and industry, and unaligned experts. Drawing on these data, we offer some suggestions to improve communication between scientists and journalists. PMID- 1917513 TI - Radioiodination and biodistribution of analogs of a calichemicin constituent. AB - Analogs of the aromatic constituent of calichemicins were labeled with 131I by exchange reactions. Radiochemical yield for methyl-4-hydroxy-5-iodo-2,3-dimethoxy 6-methylbenzoate was approx. 90%. For methyl-4-benzyloxy-2-hydroxy-3-iodo-6 methylbenzoate the yield was about 30%. Biodistribution studies were carried out in mice following intravenous administration of tracer doses. Average brain uptake of the first compound at 3 min was 0.28%, and that of the second 1.96%. Tissue distribution of the two compounds elsewhere was similar in nature. High uptake was observed initially in the liver; this reduced with time, while radioactivity in the GI-tract increased. The benzylated compound appeared potentially useful for designing a brain imaging radiopharmaceutical. PMID- 1917514 TI - Effect of Pseudomonas aeruginosa-derived pyocyanin and 1-hydroxyphenazine on pulmonary mucociliary clearance monitored scintigraphically in the baboon model. AB - The effect of products of the bacterium Pseudomonas aeruginosa on mucociliary lung clearance has been monitored in vivo in the baboon model by scintigraphy. Clearance was found to be inhibited by both 1-hydroxyphenazine and pyocyanin, and a dose-effect was illustrated by the former. This confirms previous in vitro results as well as results from work on guinea-pigs, and holds good prospects for the use of the baboon model under anesthesia in such investigations. PMID- 1917512 TI - Risk information for public consumption: print media coverage of two risky situations. AB - This study examines (1) the extent to which newspaper and magazine coverage of two risky situations included the kinds of cognitive information about risks that would help readers make risk judgments and (2) the extent to which the scientific sophistication of the audience would influence such inclusion. The two situations were a nuclear power plant accident that released a small amount of radioactive steam into the atmosphere and a report in the New England Journal of Medicine about a potential relationship between coffee consumption and pancreatic cancer. Stories about each topic in trade magazines, popular science magazines, general magazines, and both prestige and more typical daily newspapers were examined to determine the nature and extent of risk information included. The analysis found more detailed risk information in these stories than has been found in past studies, but it also suggested that sophistication of audience was not a good predictor of the presence/absence of such information. The most pronounced differences in communication strategies were found instead between topics, not across types of media. Closer examination of individual stories suggests that the variance may be attributable to differences in the way stories about the two incidents were framed by journalists. PMID- 1917515 TI - Technetium-99m-labeled platelets: comparison of labeling with a new lipid-soluble Sn(II)-mercaptopyridine-N-oxide and 99mTc-HMPAO. AB - Platelets pretinned with a neutral Sn(II)-2-mercaptopyridine-N-oxide (SN-MPO) were labeled with 99mTc and compared to those labeled with 99mTc-HMPAO. The conditions of labeling platelets, e.g. concentrations of platelets and Sn(II) MPO, 99mTc in ACD-saline or ACD-plasma media, pH and incubation time, were optimized using canine platelets. Moderate labeling efficiency was obtained with 20 micrograms of tin(II) chloride and 30 min incubation with Sn-MPO and pertechnetate. The viability of labeled platelets was determined by platelet recovery and platelet survival times in Beagle dogs. The labeling efficiency with platelets from 43 mL of blood was 62.8 +/- 7.6%. The platelet recovery was 35.7 +/- 5.0% and exponential survival time was 34.6 +/- 3.1 h compared to 43.3 +2- 12.0% and 29.5 +/- 3.3 h for 99mTc-HMPAO-labeled platelets. These values were significantly (P less than 0.01) lower than 111In-labeled platelets. Biodistribution in dogs indicates lower retention in blood, spleen and liver after some initial 99mTc excretion in urine. The platelet deposition with 99mTc platelets (Sn-MPO method) on polyurethane angio-catheters was similar to 99mTc HMPAO-labeled platelets. This study indicates that the platelets could be successfully labeled with pertechnetate in a cost-effective manner for the evaluation of thromboembolic complications. PMID- 1917516 TI - The in vivo release of 90Y from cyclic and acyclic ligand-antibody conjugates. AB - Yttrium binding ligands DOTA, caDTPA and CT-DTPA were each conjugated to monoclonal antibody B72.3, labelled with 90Y and injected into mice in order to assess the in vivo inertness of the antibody-linked 90Y-ligand complexes. Levels of 90Y in femur shafts of the DOTA-B72.3 mice were low, being approximately 7 and 44%, respectively, of levels in the femur shafts of the caDTPA-B72.3 and CT-DTPA B72.3 treated mice. This finding demonstrates the greater inertness and by implication the greater suitability for immunotherapy of the DOTA-90Y complex. PMID- 1917517 TI - Evaluation of two new bifunctional chelates for radiolabeling a parathyroid specific monoclonal antibody with In-111. AB - BB5-G1, a monoclonal antibody specific for human parathyroid cell membrane antigen was conjugated with two new ligands, BrMe2HBED and Br phi HBED and radiolabeled with 111In. We have compared the biodistribution of 111In-labeled BB5 using the new ligands to conventionally labeled (125I-labeled and 111In-DTPA labeled) BB5 in a nude mouse model. Both 111In-BrMe2HBED-BB5 and 111In-Br phi HBED-BB5 attained high parathyroid-to-blood and parathyroid-to-muscle ratios by 72-96 h. 111In-Br phi HBED-BB5 showed lower %ID/g than 111In-BrMe2HBED-BB5 in the clearance organs, the liver and kidney; renal activity had cleared significantly by 120 h. This work suggests that 111In-Br phi HBED-BB5 offers improved in vitro behavior and may be useful as a radiopharmaceutical for localizing parathyroid tissue. PMID- 1917518 TI - Evaluation of the 323/A3 monoclonal antibody and the use of technetium-99m labeled 323/A3 Fab' for the detection of pan adenocarcinoma. AB - The 323/A3 murine monoclonal antibody, initially described as reactive to breast carcinomas, is found by immunohistological analyses to have broad cross reactivity with adenocarcinomas of diverse histologic origin. The 323/A3 antigen is similar to the tumor-associated 17-1A antigen as revealed by immunoblot and cross-competition cell binding studies. We have investigated the potential use of the 323/A3 monoclonal antibody for tumor imaging as a Fab' molecule labeled with 99mTc. In vitro studies demonstrate that 323/A3 Fab' has high affinity (2-3 x 10(9) M-1) with no significant loss of immunoreactivity compared to the intact IgG. In vivo studies demonstrate that 99mTc 323/A3 Fab' can rapidly detect human breast and colon tumor xenografts growing in athymic nude mice. Distinct breast tumor visualization is observed as early as 1 h post intravenous administration with the 99mTc 323/A3 Fab'. Distinct colon tumor visualization is observed by 3 h (the earliest time point imaged). Tumor-to-blood ratios are higher for 99mTc 323/A3 Fab' than with a 99mTc-labeled nonspecific isotype-matched Fab' antibody. These results suggest that 99mTc 323/A3 Fab' can detect 17-1A antigen and may have potential clinical utility for the rapid diagnostic imaging of adenocarcinomas. PMID- 1917519 TI - Role of serum albumin as a carrier of 99mTc-complex to tumor tissue. AB - To elucidate a factor required for tumor-imaging 99mTc-labeled radiopharmaceuticals, in vivo behaviors of 99mTc-L-cysteine (99mTc-Cys) and 99mTc 2-mercaptoethylamine (99mTc-ME) were compared with that of 99mTc-DL-homocysteine (99mTc-Hcy) which had been found to accumulate in several experimental tumors. When these three complexes were intravenously injected into mice bearing Ehrlich solid tumor, their tumor affinity was found to depend on their binding ability to serum albumin; 99mTc-Hcy, the albumin-binding ability of which was highest of the three, was the most tumor-tropic. When the albumin-bound complexes of these three were injected, their tumor distributions were enlarged. These results suggest the importance of serum albumin in serving as a carrier for the transport of 99mTc Hcy-related compounds to tumor tissue. PMID- 1917520 TI - Suitability of rodent tumor models for experimental PET with L-[1-11C]tyrosine and 2-[18F]fluoro-2-deoxy-D-glucose. AB - The applicability of five different rodent tumors for experimental PET has been investigated. L-[1-11C]Tyrosine was a better indicator for the growth activity of the tumors than [18F]FDG. For experimental PET, the three mice models studied appeared inappropriate; the Lewis lung tumor and the fibrosarcomateous FIO 26 had too low a tyrosine utilization, while the lymphosarcomateous LY showed insufficient tumor-to-background ratios. Of the two rat models, the necrotic Walker 256 carcinosarcoma was less suitable. By using L-[1-11C]tyrosine, the solid, rhabdomyosarcoma tumor offers good possibilities of monitoring therapeutic interventions with PET. PMID- 1917521 TI - Comparison of different methods for LDL isolation and radioiodination on liver LDL receptor binding in vitro. AB - Lipoproteins were isolated either by immunoaffinity chromatography (LDL and VLDL) or ultracentrifugation (LDL). Purified lipoproteins were labeled with 123I using either Iodogen or iodine-monochloride (IC1) each followed by purification with gel-chromatography or dialysis (total of 4 combinations). Lipoprotein concentrations of 0.1-6 micrograms protein/mL were used for direct binding assays investigating the specific binding of labeled lipoproteins (in the presence of a 50-fold excess of unlabeled lipoproteins) to human liver apo-B, E-receptors. In separate experiments displacement of bound 123I-lipoproteins (labeled by the methods mentioned) by unlabeled ones was studied. The binding capacities estimated by Scatchard analysis were similar to each other (141-163 ng protein bound/mg liver plasma membrane protein) independent from the method used for isolation and labeling. Also the affinity constants were very similar and ranged from 0.9 to 1.7 micrograms protein/L. It is concluded that immunoaffinity chromatography or ultracentrifugation for isolation of lipoproteins and the Iodogen or IC1-method for radiolabeling can be recommended to be equally good for in vitro receptor investigation. PMID- 1917522 TI - Imaging of human ovarian tumour xenografts in nude mice using a novel 111In labelled monoclonal antibody (10B). AB - Monoclonal antibody (mAb) 10B, directed against the human ovarian adenocarcinoma cell line, HEY, was conjugated with cyclic DTPA anhydride and labelled with 111In. The biodistribution of 111In-DTPA-10B was determined in non-tumour bearing mice and mice bearing subcutaneous (s.c.) and intraperitoneal (i.p.) HEY tumours. The radiolabel was preferentially targeted to s.c. and i.p. tumours in comparison with a control mAb. 111In-DTPA-2G3, which does not bind to HEY cells. Among normal organs, the predominant uptake of radiolabel was into liver and kidney. Subcutaneous tumours were successfully imaged using external gamma scintigraphy following i.v. injection of 111-In-DTPA-10B. The results suggest that 111In-DTPA 10B may be a useful agent for the diagnostic imaging of tumour masses in patients with ovarian cancer. PMID- 1917523 TI - Dosimetry and pharmacokinetics of monoclonal antibody A6H with human renal cell carcinoma xenografts: single dose study. AB - Implantable miniature thermoluminescent dosimeters and conventional biodistribution analysis were used to determine the locally absorbed radiation dose delivered to three morphologically distinct human renal cell carcinoma xenografts (TK-39, TK-82 and TK-177C; N = 87) following a 50 microCi infusion of 131iodine-labeled monoclonal antibody A6H. Xenografts were clearly detected by radioimmuno-scintigraphy. Pronounced differences were noted among the three xenografts in MAb pharmacokinetics and in the locally absorbed irradiation doses which ranged from 2 to 5 cGy per injected microCi of 131iodine-labelled A6H. PMID- 1917524 TI - Lipophilic 99mTc-nitride radiopharmaceuticals as potential myocardial imaging agents. AB - Monocationic 99mTc-nitrido complexes of a variety of diphosphine ligands have been prepared and the in vivo distribution of such cations has been examined in Sprague-Dawley rats. These complexes show initially high myocardial uptake with subsequent wash-out in this animal model. The lack of myocardial retention can be attributed to the facile in vivo reduction of these cations. PMID- 1917525 TI - Preparation, radiolabeling and biodistribution of a new class of bisaminothiol (BAT) ligands as possible imaging agents. AB - In developing new ligands as potential brain and heart perfusion imaging agents two ligands based upon N2S2 donor atoms with the biphenyl backbone were synthesized. Biphenyl-2,2'-bis(N-1-amino-2-methyl-propane-2-thiol) (BP-BAT-TM) and biphenyl-2,2'-bis(N-1-amino-2-ethyl-butane-2-thiol) (BP-BAT-TE) form stable, neutral and lipid soluble complexes with [99mTc]pertechnetate in the presence of tin(II) tartarate as a reducing agent. The [99mTc]BP-BAT-TM complex penetrates the blood-brain barrier following i.v. injection into rats. Washout from the brain is fast, indicating no retention. The biodistribution of [99mTc]BP-BAT-TE in rats showed an initial heart uptake (0.8%/organ, at 2 min) and a slow washout (0.74% at 15 min). No brain uptake was found (0.05%). Significant uptake and retention in liver was observed. An imaging study of [99mTc]BP-BAT-TE in a monkey showed no brain uptake and a clear indication of liver uptake and gall bladder clearance. These results indicate that this ligand system may be suitable as the basic core structure for the development of new imaging agents. Further studies with structural variations in the biphenyl backbone are warranted to develop new 99mTc imaging agents for clinical applications. PMID- 1917527 TI - Synthesis and biodistribution of 123I N-(2-aminoethyl)-5-iodo-2 pyridinecarboxamide (Ro 43-0463), a monoamine oxidase B inhibitor. AB - N-(2-Aminoethyl)-5-iodo-2-pyridinecarboxamide (Ro 43-0463) was radiolabeled with 123I in 22% radiochemical yield by anionic isotopic exchange in acidic medium. Biodistribution studies of this radioligand in rats showed peak brain uptake of 0.50% of the injected dose at 30 min and slow washout over 60 min. PMID- 1917526 TI - Evaluation of quaternized and neutral muscarinic receptor ligands in normal and DES-treated rat. AB - The localization of quaternized muscarinic receptor (mAChR) antagonists, [11C]methyl tropanyl benzilate ([11C]MTRB) and [11C]methyl quinuclidinyl benzilate ([11C]MQNB), in rat pituitary was compared to that of [11C]tropanyl benzilate ([11C]TRB), a neutral antagonist. The quaternized ligands localize via a mAChR-mediated mechanism as shown by 60% reduction in radioactivity concentrations in the presence of QNB. [11C]TRB appears to localize primarily by a non-mAChR specific mechanism. Induction of pituitary prolactinomas by diethylstilbestrol resulted in a reduction of [11C]MTRB pituitary localization compared to normals. Elevated serum prolactin levels due to prolactinoma presence had no measurable effect on myocardial [11C]MTRB uptake or on KD values. Bmax values for myocardial mAChR were similar for controls and for DES exposure of 10 weeks. PMID- 1917528 TI - Improved monoclonal antibody tumor/background ratios with exchange transfusions. AB - Blood exchange transfusions were performed in nude rats with subcutaneous HTB77 human ovarian carcinoma xenografts in an attempt to improve specific monoclonal antibody (MoAb) tumor/non-tumor uptake ratios. Animals were injected intravenously with both 131I-5G6.4 specific and 125I-UPC-10 non-specific MoAb. Twenty-four hours later 65-80% of the original blood was exchanged with normal heparinized rat blood and then these rodents were sacrificed. Exchange transfusion significantly (P less than 0.05) decreased normal tissue activities of 131I (except for muscle) by 63-85%, while tumor activity decreased only 5%. Tumor to background ratios increased from 0.1-0.8 to 2.3-6.3. Exchange transfusions substantially enhance tumor/normal tissue antibody uptake ratios and, along with plasmapheresis, may be useful in enhancing antibody localization in vivo, particularly for therapy. PMID- 1917529 TI - Two new cases of Hb Denmark Hill [alpha 95(G2)Pro----Ala] discovered in south west France: electrophoretical and chromatographical considerations. PMID- 1917530 TI - A new abnormal variant, Hb Yahata or beta 112(G14)Cys----Tyr, found in a Japanese: structural confirmation by DNA sequencing of the beta-globin gene. PMID- 1917532 TI - Hb St. Francis [beta 121(GH4)Glu----Gly]: a new mutation at the same site as Hb D Los Angeles. PMID- 1917531 TI - Beta-thalassemia, HB S-beta-thalassemia and sickle cell anemia among Tunisians. AB - We analyzed the mutations present in 19 patients with beta-thalassemia major, in 11 patients with Hb S-beta-thalassemia, and the beta S haplotypes of 34 patients with sickle cell anemia. The study included 84 relatives. Dot-blot analysis of amplified DNA with various specific oligonucleotide probes identified 11 different known beta-thalassemia mutations and frameshifts; a new frameshift at codons 25/26 (+T) was detected through sequencing of amplified DNA. The common beta-thalassemia mutations at codon 39 (C----T) and at IVS-I-110 (G----A) were also most prevalent among the Tunisian patients, while the milder T----C mutation at IVS-I-6 was not found. All mutations cause a beta 0-thalassemia or a severe beta + -thalassemia [T----A at -30; IVS-I-5 (G----A); IVS-I-110 (G----A)] which explains the need for regular blood transfusions in the thalassemia major and S beta-thalassemia patients. Nearly all sickle cell anemia patients carried the beta S mutation on a chromosome with haplotype 19 (or Benin) and all had severe anemia with sickling complications. Identification of the beta S haplotype was through dot-blot analysis with oligonucleotide probes that detect mutations in the G gamma and A gamma promoter sequences, specific for this haplotype. PMID- 1917533 TI - Cell design for reducing the amount of sickle cell hemoglobin needed per gelation assay. PMID- 1917534 TI - Hb E [beta 26(B8)Glu----Lys] in a Czechoslovakian family. PMID- 1917535 TI - Hb Koln or alpha 2 beta 2(98)(FG5)Val----Met in a Czechoslovakian family. PMID- 1917536 TI - A third instance of the high oxygen affinity variant, Hb Heathrow [beta 103(G5)Phe- greater than Leu]: identification of the mutation by mass spectrometry and by DNA analysis. AB - Hb. Heathrow [beta 103(G5)Phe- greater than Leu] was identified in an Englishman with a life-long history of polycythemia, his father had been similarly affected. A hemoglobin variant was suspected from the high oxygen affinity of the patient's blood. The Hb Heathrow abnormal beta chain was resolved from the normal beta chain by high performance liquid chromatography, and the abnormal peptide and the amino acid replacement were identified by mass spectrometry. The corresponding base change (C- greater than G at codon 103) was demonstrated by sequence analysis of the polymerase chain reaction amplified exon 2 of the genomic beta globin gene. This is only the third known instance of Hb Heathrow. PMID- 1917537 TI - A new unstable and low oxygen affinity hemoglobin variant: Hb Stanmore [beta 111(G13)Val----Ala]. AB - Hb Stanmore is a new hemoglobin variant with the amino acid substitution beta 111(G13)Val----Ala. It is unstable and has a low oxygen affinity. The propositus (of Italian nationality) is a double-heterozygote for Hb Stanmore and beta(0) thalassemia. PMID- 1917538 TI - The usefulness of sequence analysis of amplified DNA for the identification of delta chain variants. AB - A method of identifying delta chain variants using relatively small volumes of blood is described. The procedure consists of the amplification of two segments of genomic DNA with two sets of delta chain specific primers and sequencing of the three exons (exons 1, 2, and 3) which are part of the amplified DNA segments. Data for three delta chain variants present in seven adult heterozygotes are presented. PMID- 1917539 TI - Hb Geelong [beta 139(H17)Asn----Asp]. AB - Hb Geelong [beta 139(H17)Asn----Asp] was detected in a German woman of Polish Russian descent. It is an unstable variant which appears to increase the severity of a beta (+)-thalassemic phenotype in the propositus. The electrophoretic properties of Hb A and Hb Geelong are similar on cellulose acetate in both acidic and alkaline conditioning. The electrophoretic mobility and the amino acid analysis of beta XT-14 indicated the substitution Asn----Asp at beta 139. The sequence of beta XT-14 was confirmed by dansyl-Edman degradation. The slight increase observed in the P50 of whole blood is not intrinsic to the beta 139 substitution, but is thought to result from an increased 2,3-diphosphoglycerate level in response to anemia. No family studies were possible to investigate the mode of inheritance of either beta (+)-thalassemia or Hb Geelong in the propositus. Synthetic globin chain ratios suggest that impaired synthesis of the variant globin chain is partially responsible for the low level of Hb Geelong in peripheral blood. PMID- 1917540 TI - Hb Luxembourg [alpha 24(B5)Tyr----His], Hb Maputo [beta 47(CD6)Asp----Tyr], and Hb Fukuyama [beta 77(EF1)His----Tyr]. PMID- 1917541 TI - Incidence of double-band HSRs in chromosome 1 of the house mouse, Mus musculus musculus, from Oland (Sweden): a population study. AB - The incidence of homogeneously staining regions (HSRs) in chromosome no. 1 of Mus musculus musculus was ascertained by C-band staining on chromosomes of mice collected on the island of Oland (Sweden). A total of 157 specimens from eight localities representing three regions were analysed. Mice with enlarged chromosome no. 1, due to double-band HSRs, were found in all three regions. The overall incidence of HSR-bearing chromosomes was 6.7% in mice collected on Oland in 1988. In the two largest samples, the incidences were 14.5% (n = 31) and 3.9% (n = 76). With regard to HSR size, several different variants were present. Size differences were found for the proximal as well as for the distal HSR band. Different mutant forms were found even within one population (a single farm). The implications of these findings are discussed. PMID- 1917542 TI - In situ localization of the Antennapedia gene on the chromosomes of nine Drosophila species of the obscura group. AB - The homeotic Antennapedia gene, cloned from the genomic DNA of D. subobscura, was localized on the polytene chromosomes of nine species of the Drosophila obscura group. In all of them, the probe used hybridized on chromosomes equivalent to the E element of Muller's terminology. These results are consistent with the idea that single copy genes do not move around the genome and that chromosomal elements have conserved their genetic identity during evolution. PMID- 1917544 TI - Effect of extra Y chromosome on number and fluctuating asymmetry of sternopleural bristles in Drosophila melanogaster. AB - The effect of the extra Y chromosome on the number and fluctuating asymmetry of sternopleural bristles in Drosophila melanogaster was studied at two temperatures, 18 degrees C and 25 degrees C, in the stock In(l)wm4/y+Y. The extra Y chromosome significantly increased the number of sternopleural bristles especially in the lateral areas of the sternopleura, which hampered the analysis of the effect of the extra Y chromosome on fluctuating asymmetry. The formula used was one which assumes that the fluctuating asymmetry is dependent on the total number of bristles. It was found that the extra Y chromosome increased fluctuating asymmetry at 18 degrees C but decreased it at 25 degrees C. There was less fluctuating asymmetry in females than in males. It appears that the extra Y chromosome has an effect on the temperature which is most favourable to the development of the sternopleural bristles. PMID- 1917543 TI - Chromosomal localization of the glucose phosphate isomerase (GPI) gene in cattle, sheep and goat by in situ hybridization--chromosomal banding homology versus molecular conservation in Bovidae. AB - A porcine genomic glucose phosphate isomerase (GPI) DNA probe was used for in situ hybridization with metaphase chromosomes in cattle, sheep and goat. The probe gave distinct signals on the q22----proximal part of the q24 segment of chromosome 18, 14 and 18 in cattle, sheep and goat, respectively, indicating the location of GPI gene. The three species belong to the family Bovidae and have high resemblance in chromosome banding patterns. The localization of the GPI locus to the same site on chromosomes with almost similar banding patterns suggests high degree of homology at these sites in the three species. Correlation between banding homologies and possible similarities at the molecular level is discussed. PMID- 1917545 TI - Studies of the species barrier between Drosophila madeirensis and Drosophila subobscura. II. Genetic analysis of developmental incompatibilities in hybrids. AB - The genetic analysis of two abnormal characters, extra sex combs and abnormal head shape in hybrids between Drosophila madeirensis and Drosophila subobscura, revealed a major effect of the X chromosome in both cases. Autosomes also play a role in determining these abnormalities, the E chromosome in case of extra sex combs, the E and O chromosomes in case of abnormal head shape. Autosomes do not cause the two abnormal characters, without interacting with the X chromosome. PMID- 1917546 TI - Interaction of master mind, big brain, neuralized and Notch genes of Drosophila melanogaster as expressed in adult morphology. PMID- 1917547 TI - Sterility of male and female hybrids of Drosophila virilis and Drosophila lummei. AB - The sterility of interspecific hybrids between the sibling species Drosophila virilis and D. lummei was tested in reciprocal F1s and different second generation combinations of cytoplasm, sex chromosomes and autosomes. Males with motile sperm and females with at least one mature egg were scored as fertile. When D. virilis was the mother, about 5 per cent of the F1 male progeny was sterile, the reason being that the X of D. virilis was weakly incompatible with the heterozygous second, fourth and fifth chromosomes. The F1 males carrying the X chromosome of D. lummei were all fertile. The X chromosome of D. lummei, and in particular its species-specific double inversion In(1)a + b, nevertheless caused sterility in 70 per cent of males in the presence of homozygous autosomes of D. virilis. Sterility was rare among the females, although some weakly disadvantageous X versus autosome and autosome versus autosome interactions were detected. The male and female hybrid sterilities were based on different genetic systems. The results emphasize the central role of the X chromosome in hybrid male sterility. PMID- 1917548 TI - Polymorphism at the Adh and alpha Gpdh loci in Drosophila melanogaster: effects of rearing temperature on developmental rate, body weight, and some biochemical parameters. AB - The role of developmental time in the world-wide cline of Adh and alpha Gpdh allele frequencies of Drosophila melanogaster, and the relationship with weight and some biochemical characters, were investigated. Experimental strains were constructed with different combinations of Adh and alpha Gpdh alleles but with similar genetic background. Developmental time, adult weight, protein-and triglyceride-content, and ADH and alpha GPDH enzyme activity were measured at a rearing temperature of 20, 25 and 29 degrees C. Genotype effects were found in all studied characters. In general the developmental times of genotypes were: AdhFF less than AdhFS less than AdhSS and alpha GpdhFF greater than alpha GpdhFS = alpha GpdhSS. Developmental time and adult weight were strongly affected by rearing temperature. Triglyceride content and ADH and alpha GPDH enzyme activity were slightly affected by temperature. Interactions between genotype and temperature effects were found for developmental rate, adult weight and protein content. No trade off was observed between developmental time on the one hand and adult weight, protein- and triglyceride-content, and ADH and alpha GPDH enzyme activity on the other hand. It is argued that developmental rate differences might be one of the underlying mechanisms of the world-wide cline of the Adh and alpha GPdh allele frequencies. PMID- 1917549 TI - Genetic specification of life span and self-fertility in recombinant-inbred strains of Caenorhabditis elegans. AB - The genetic basis of life-span and age-specific fertility has been analysed using recombinant-inbred strains of the nematode Caenorhabditis elegans. Estimates of narrow-sense heritability range from 0.05 to 0.36 for life span and from 0.36 to 0.49 for total self-fertility. Positive phenotypic and genetic correlations for life span and total fertility were also observed, although in most cases the correlations were not significant. In general, age-specific hermaphrodite fertility was positively correlated with fertility on contiguous days but was negatively correlated with fertility on more distant days. We estimate that a minimum of two to three genes specify each of these traits in this genetic background. Three single-gene markers were used to generate strain distribution patterns, and two of these were found to be linked with loci that specify life span and/or fertility. We also saw evidence for a significant environmental component affecting self-fertility. PMID- 1917550 TI - Quantitative analysis of genetic differentiation among European and Chilean strains of Drosophila subobscura. AB - An analysis of the interpopulational differences observed between four European and four Chilean stocks of Drosophila subobscura, with regard to wing size, egg to-adult development time and preadult viability, shows highly significant differences between the eight stocks irrespective of the continent from which the flies are derived. The divergence of the local populations with regard to the quantitative traits described here, supplements other evidence of interpopulational differences in mating activity, chromosomal and enzyme polymorphisms. These together indicate that the evolutionary process that promotes race formation is relatively rapid, bearing in mind that D. subobscura was detected for the first time in South America in 1978. PMID- 1917551 TI - Breeding behaviour of pilot whales revealed by DNA fingerprinting. AB - Most species of whale spend the majority of their lives well away from land, are capable of migrating over large distances and are difficult to identify individually. However, conservation measures require a detailed understanding of their social structure, breeding behaviour and migration patterns. The advent of DNA fingerprinting permits a systematic investigation of such parameters. In the Faeroe Islands there exists a traditional harvest of long-finned pilot whales (Globicephala melas), in which intact social groups (pods) are captured. This affords a unique opportunity to study genetic relationships within and between pods. We report here on a paternity analysis, using DNA fingerprinting, of mother fetus pairs and males sampled from complete pods. In addition, a single, highly polymorphic minisatellite locus was used to infer degrees of relatedness between groups of fetuses and females. Taken together, our results suggest that pods consist of closely related adult females and their offspring. Sexually mature males either move frequently between pods or remain in their natal pod but refrain from mating with female relatives. Whichever hypothesis is correct, the data suggest that each male spends only a few months with the female post-mating and individual males often father several fetuses within a pod. PMID- 1917552 TI - The evolutionary history of Drosophila buzzatii. XXI. Cumulative action of multiple sterility factors on spermatogenesis in hybrids of D. buzzatii and D. koepferae. AB - The genetic basis of sterility in male hybrids of Drosophila buzzatii and D. koepferae has been investigated by assessment of the effects on spermatogenesis of substituting separate chromosome segments of the recipient species with the homologous material from the donor species, either in heterozygous (autosomes) or hemizygous (X chromosome) condition, after successive backcrossing of hybrid females to either parental species. Introgressed segments were identified by the characteristic asynapsis of the polytene chromosomes in their heterospecific regions. Except for one case, the introgression of chromosome segments either from autosome 3, 4, or 5 brings about sterility only when the introgressed segment exceeds a minimum size (threshold size). Segments of equal size frequently produce similar abnormalities, whose severity increases with the size of the introgressed segment. Apparently, throughout these autosomes of D. buzzatii and D. koepferae there are many non-allelic, minor sterility genes, whose individual segregation cannot be recognized phenotypically, and which act cumulatively on the same characteristics of spermatogenesis, each contributing a small effect to the phenotype. Accordingly, these genes should be considered as polygenes, and the type of sterility they bring about should be properly designated polygenic sterility. PMID- 1917553 TI - Ecological and genetic models of host-pathogen coevolution. AB - A model is presented to analyse the forces that maintain genetic polymorphism in interactions between host plants and their pathogens. Genetic variability in hosts occurs for specific resistance to different pathogen races and variability in pathogens occurs for specific virulence to different host races. The model tracks both fluctuating population sizes and changing gene frequencies. Analyses over a range of parameters show that ecological and demographic factors, such as birth and death rates, often have a more profound effect on the amount of polymorphism than genetic parameters, such as the pleiotropic costs of resistance and virulence associated with different alleles. A series of simple measures are proposed to predict the amount of genetic polymorphism expected in particular host-pathogen interactions. These measures can be used to develop and test a comparative theory of genetic polymorphism in host-pathogen coevolution. PMID- 1917554 TI - Geographic origin of the US and Brazilian Aedes albopictus inferred from allozyme analysis. AB - A survey of genetic variation using allozymes was conducted on 57 populations of Aedes albopictus, an Asian mosquito that was introduced into the US and Brazil in the mid-1980s. Our objective was to quantify the patterns of genetic variation among its populations and to use that information to trace genetically the geographic origin of the US and Brazilian populations. Populations from the various regions were genetically distinct from one another. Populations from within a region were genetically similar to one another, which resulted in a significant positive correlation between geographic and genetic distances. A discriminant analysis of allele frequencies separated populations from the various countries into nine non-overlapping clusters; the US, Japanese, Chinese and Brazilian populations formed closely placed, but distinct, clusters. The probability of assigning a population to the correct country was 98 per cent. The US and the Brazilian populations were closest in terms of genetic distance from the Japanese populations. Based on discriminant and genetic distance analyses, we conclude that the US and the Brazilian Aedes albopictus originated in Japan. PMID- 1917555 TI - Analyses of survival rate of unresectable pancreatic adenocarcinoma in aspect of data analyses. AB - Using Cox's proportional hazard model and Weibull's proportional hazard model and taking into account the covariates involved, estimation of survival time was made on 94 confirmed deceased cases of unresectable pancreatic adenocarcinoma (excluding cases of cystadenocarcinoma) from the data of their admission for confirmation of diagnosis. The following results were obtained: 1) The covariates which were related to the prognosis of unresectable pancreatic adenocarcinoma were presence or absence of metastasis to the liver and lung, type of treatment for obstructive jaundice, and whether in such treatment, chemotherapy, or radiotherapy was conducted. 2) Estimation of the survival time after adjusting these factors showed that the median survival time was 57 days in untreated cases with metastasis, 107 days in untreated cases without metastasis, 284 days in cases with metastasis in which surgical treatment for obstructive jaundice, chemotherapy, and radiotherapy was administered, and 350 days in cases without metastasis in which the same positive treatment was administered. It can therefore be deduced that multidisciplinary treatment is effective in prolonging life. PMID- 1917556 TI - Ultrastructural changes in aging rat tracheal gland. AB - Ultrastructural differences in the tracheal gland between young and aged rats were studied. Marked differences were observed in the serous cells between the young (8-17 week-old) and the aged (20-30 month-old) subjects. The secretory granules of the serous cells of the young subjects were homogeneously electron dense, whilst those of the aged subjects had a bizonal appearance. These bizonal granules contained abundant mucous material. The trans Golgi network of the aged rat serous cells was more developed and formed a fine meshwork in comparison with that of the young subjects. In the aged subjects, findings indicate alterations not only in the function of the Golgi apparatus including formation of secretory granules and addition of terminal sugars to the secretory protein but also the histochemical and ultrastructural properties of the secretory material. The changes in the Golgi apparatus are possibly responsible for depression of the tracheal host defense mechanism and might explain why various airway diseases increase with aging. PMID- 1917557 TI - Superficial Sylvian veins as landmarks for operation of middle cerebral artery aneurysms. AB - A retrograde approach to aneurysms located at the middle cerebral artery bifurcation which uses the superficial Sylvian veins as landmarks is described. Fifty patients with 51 aneurysms were operated on using this technique. This method made it easier for surgeons to decide where to enter the Sylvian fissure for dissection of the middle cerebral artery branches and to secure the parent artery. PMID- 1917558 TI - Parathyroid tumors in atomic bomb survivors in Hiroshima: first report of surgical cases, 1956-1988. AB - Seventeen patients with parathyroid gland tumors underwent surgical resection at the Hiroshima University Hospital between 1956 and 1988. Three of them where born after the atomic bomb explosion, and 6 of the remaining 14 patients (42.9% of the total- a high proportion) were atomic bomb survivors. Because parathyroid gland tumors and hyperparathyroidism are assumed to develop in patients who have been exposed to radiation after a long latent period, it is necessary to anticipate the possible occurrence of these diseases in atomic bomb survivors. The present paper is the first to report surgically extirpated parathyroid gland tumors in atomic bomb survivors. PMID- 1917559 TI - Sebaceous epithelioma in the external auditory meatus: a case report. AB - We report a rare case of sebaceous epithelioma(SE) in the external auditory meatus of an 84-year-old woman. The tumor, measuring 1.5 cm in diameter, was hemispherical, yellowish-brown, elastic and hard. It was removed surgically without complications and there has been no recurrence two years postoperatively. The histopathologic findings were characteristic of a sebaceous epithelioma. The controversy over the origin of this tumor is discussed. PMID- 1917560 TI - The effect of bovine brain gangliosides on essential tremor. AB - We reported the case of a 74-year-old woman suffering from essential tremor for 20 years which was treated effectively with purified bovine brain gangliosides containing GM1, GD1a, GD1b and GT1b gangliosides. The trials of the treatment were conducted twice, 40 mg and 20 mg gangliosides per day respectively administered intramuscularly. Essential tremor dramatically improved with gangliosides on the second day of treatment, suggesting that the effect of gangliosides was not induced by neuronal sprouting or regeneration. It is speculated that a certain type of essential tremor is a reversible disease of membrane disorder. PMID- 1917561 TI - Blocking of the amino groups of histone proteins by glucose. PMID- 1917562 TI - Protection against salicylate-induced hepatic injury by zinc. A histochemical and biochemical study. AB - Female Wistar rats received an oral dose of 700 mg salicylic acid/kg body wt., given as sodium salicylate. Some of the salicylate-treated rats received two subcutaneous injections of 100 mumol kg-1 ZnCl2 (24 h before and simultaneously with the salicylate administration). Other animals were given one subcutaneous injection of 100 mumol kg-1 ZnCl2 simultaneously with the salicylate treatment. Control rats were similarly injected with ZnCl2. Twenty four hours after salicylate treatment, serum and livers were taken for histochemical and biochemical analysis. The most remarkable effects of the treatment were enrichment of lipid droplets and iron and a reduction of glycogen, particularly in the periportal hepatocytes. The effects of salicylate were partially prevented by two ZnCl2 injections. The protective effects of ZnCl2 may be due to lower iron uptake into hepatocytes and by the induction of zinc metallothionein, which can serve as a scavenger for oxygen radicals. PMID- 1917563 TI - Immunocytochemical localization of heparan sulphate proteoglycan in the rat submandibular gland. AB - Heparan sulphate proteoglycan is the predominant proteoglycan synthesized by the parenchymal cells of the rat submandibular gland. A polyclonal antibody was used to localize this proteoglycan in the adult rat submandibular gland. Localization was accomplished by indirect immunoperoxidase cytochemistry at the light and electron microscopic levels. Heparan sulphate proteoglycan was localized in a continuous, linear pattern in the lamina densa of the basement membrane surrounding all of the epithelial components of the gland as well as the basement membrane of the capillaries and small arterioles in the glandular stroma. In addition, heparan sulphate proteoglycan was seen in vesicles and pits along the acinar cell basal plasmalemma adjacent to the basement membrane and in the endoplasmic reticulum and Golgi apparatus of the acinar cells. PMID- 1917564 TI - Immunohistochemical distribution of MAM-3 and MAM-6 antigens in developing salivary glands of the human fetus. AB - The immunohistochemical expression of MAM-3 and MAM-6 antigens was studied developing human fetal salivary gland removed at autopsy of 22 normal fetuses of varying maturity (10-40 weeks of gestation). The onset of functional maturation in the fetal gland was seen at 21 weeks of gestational maturity. The acini and ducts then underwent distinct alterations in antigen expression with growth and maturation until the late developmental stage (33-40 weeks of gestation) when they resemble the adult salivary gland. The role of maturing duct cells in histogenesis of salivary gland tumours is discussed. PMID- 1917565 TI - Metabolic variability within individual fibres of the cat tibialis posterior and diaphragm muscles. AB - Variance in succinate dehydrogenase activity along the transverse and longitudinal axes of fibres from the cat tibialis posterior and diaphragm muscles was determined in order to estimate the three-dimensional distribution of mitochondria within single fibres. The variance (coefficient of variation) in succinate dehydrogenase activity along the transverse fibre axis was greatest in type IIB fibres from both muscles. Intracellular compartmentalization (i.e. subsarcolemmal vs central core differences in succinate dehydrogenase activity) was observed only in type II fibres from the tibialis posterior; the succinate dehydrogenase activity of the subsarcolemmal region was significantly greater than that of the central core. The extent of succinate dehydrogenase variance along the longitudinal fibre axis was dependent on the total length of the fibre segment analyzed, the muscle, and fibre type. The coefficient variation for short fibre segments, i.e. 40 microns, was significantly lower than that for much longer fibre segments (840 microns). Significant differences in the coefficient variation for 840 microns fibre segments were observed between the diaphragm and tibialis posterior muscles. The longitudinal variance in succinate dehydrogenase activity was higher in diaphragm muscle fibres. The succinate dehydrogenase variance along the longitudinal axis of type II fibres was higher in diaphragm muscle fibres. The succinate dehydrogenase variance along the longitudinal axis of type II fibres was significantly greater than that of the type I fibre population. These results indicate that mitochondria are heterogeneously distributed within muscle fibres. Possible functional implications of such intrafibre metabolic variance are discussed. PMID- 1917566 TI - Detection of p24 in HIV-1 infected cells embedded in LR White and Lowicryl K4M. AB - In this study we present a postembedding on-grid immunogold labelling procedure for the ultrastructural localization of the HIV-1 core protein p24. HIV-1 infected cells were fixed in 0.1% glutaraldehyde, incompletely dehydrated and embedded in LR White or in Lowicryl K4M. Antigenic sites were detected by incubation of ultrathin sections with primary mouse monoclonal antibody anti-HIV 1 p24, followed by the secondary antibody goat anti-mouse IgG coupled to 10nm gold particles. Antigenicity of p24 was found to withstand the applied fixation and was shown to be preserved in LR White as well as in Lowicryl. The described procedure permits the uncomplicated and easy detection of p24 in HIV-1 infected cells and tissues. PMID- 1917567 TI - Three-dimensional ultrastructure of anionic sites of the glomerular basement membrane by a quick-freezing and deep-etching method using a cationic tracer. AB - The ultrastructure of anionic sites in the lamina rara externa (LRE) of rat glomerular basement membrane (GBM) was studied in three dimensions by a quick freezing and deep-etching method using polyethyleneimine (PEI) as a cationic tracer. Results were compared with those obtained with conventional ultrathin sections examined by transmission electron microscopy. Examination with the quick freezing and deep-etching method was done without (group 1) or with (group 2) contrasting/fixation with a phosphotungstic acid and glutaraldehyde mixture and post-fixation with osmium tetroxide, which were necessary for visualization of PEI particles by conventional ultrathin sections. Using the quick-freezing and deep-etching method without following contrasting/fixation and post-fixation (group 1), many PEI particles were observed to decorate around fibrils, which radiated perpendicularly from the lamina densa to connect with the podocyte cell membrane. The arrangement of PEI particles was not as regular as that previously reported using conventional ultrathin sections. In contrast, the tissue that was studied with quick-freezing and deep-etching followed by contrasting/fixation and post-fixation (group 2) showed a shrunken appearance. The arrangement of PEI particles was regular (about 20 particles/1000 nm of LRE) as that previously observed using conventional ultrathin sections. However, the number of PEI particles on the LRE was markedly decreased and interruption of decorated fibrils was prominent, as compared with group 1. Ultrastructural examination using conventional ultrathin sections with contrasting/fixation and post-fixation (group 3) demonstrated PEI particles on the LRE in reasonable amounts (18-21 particles/1000 nm of LRE) with fairly regular interspacing (45-65 nm) as reported previously.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917568 TI - Histochemical studies on the mechanism of macromolecule leakage across the glomerular capillary wall. Barrier effect of the anionic groups of the capillary wall against the serum protein leakage. AB - For the purpose of revealing the barrier effect of the anionic groups of glomerular capillary wall against the serum protein leakage, morphologic and histochemical observations were made on the rat kidney perfused in situ with three kinds of cationic macromolecules different in chemical characteristics followed by blood flow restoration. The polyethyleneimine perfusion resulted in the complete disapperance of ionized anionic groups of glomerular capillary and the massive protein leakage through glomeruli by blood flow restoration. Cationic ferric colloid perfusion induced moderate protein leakage, and avidin perfusion was less in neutralization effect of anionic groups and the protein leakage was of least. The protein leakage from glomeruli, however, was stopped or markedly suppressed soon after the blood flow restoration by the newly formed functioning anionic barrier probably by some particular serum protein deposition. The findings indicate that the deionization of the glomerular capillary wall will not be responsible for the persistent albuminuria. PMID- 1917569 TI - Immunochemical and immunohistochemical studies, using antisera against porcine 25 kDa amelogenin, 89 kDa enamelin and the 13-17 kDa nonamelogenins, on immature enamel of the pig and rat. AB - Enamel proteins were extracted from the newly formed layer of immature porcine enamel, and the 25 kDa amelogenin, 89 kDa enamelin and 13-17 kDa nonamelogenins were purified. Specific antisera were raised against these proteins. Antibodies specific to the C-terminal region (residues 149-173) of the 25 kDa amelogenin were generated by absorption of the anti-25 kDa amelogenin serum with 20 kDa amelogenin, which contains residues 1-148 of the antigen. Immunoelectro-transfer blotting of the extracted porcine enamel proteins showed that the anti-25 kDa amelogenin serum recognized the 25 kDa and other low and high molecular weight amelogenins. The C-terminal specific anti-25 kDa amelogenin serum reacted only with amelogenins having molecular weights over 23 kDa. The anti-89 kDa enamelin serum recognized the 89 kDa enamelin and lower molecular weight proteins, but neither the amelogenins nor the 13-17 kDa nonamelogenins. The antiserum against the 13-17 kDa nonamelogenins showed no cross reactivity to the 89 kDa enamelin, but recognized higher molecular weight nonamelogenins. In immunohistochemical preparations of the porcine tooth germs, the 25 kDa amelogenin-like immunoreactivity over immature enamel decreased in a gradient from the enamel surface to the middle layer. In the inner layer immunoreactivity was concentrated over the prism sheaths. The C-terminal specific 25 kDa amelogenin-like immunoreactivity was intense at the outer layer of immature enamel and decreased sharply toward the middle layer. Prism sheaths were intensely stained by the antiserum to the 13-17 kDa nonamelogenins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917570 TI - Multiple peptide immunoreactivities in the nervous system of Aeschna cyanea (Insecta, Odonata). An immunohistochemical study using antisera to cholecystokinin octapeptide, somatoliberin, vasoactive intestinal peptide, motilin and proctolin. AB - By use of the indirect immunoperoxidase method, the brain, the suboesophageal ganglion and the corpora cardiaca of the dragonfly Aeschna cyanea have been shown to be immunoreactive to proctolin antiserum and to several mammalian peptide antisera including unsulfated cholecystokinin octapeptide (CCK-8 NS) (Andries et al. 1989), vasoactive intestinal peptide (VIP), human somatoliberin (hGRF) (Andries et al. 1984) and motilin antisera. Immunohistochemical studies have been performed on material fixed in a solution of picricacid paraformaldehyde or in Bouin Hollande's sublimate solution. Antisera were applied on alternate sections or, according to the elution-restaining method of Tramu et al. (1978), one after another on the same section. Multiple peptide immunoreactivities appear expressed in the brain and the suboesophageal ganglion. Cells reactive to both hGRF and VIP antisera show also gastrin/CCK-like immunoreactivity and some of them are also detected by motilin antiserum. Besides, some cells immunopositive to CCK-8 NS and motilin antisera do not show hGRF or VIP immunoreactivity. At least, two pairs of protocerebral cells appear immunoreactive to both CCK-8 NS and proctolin antisera. Therefore, the present observations support our previously developed idea (Andries et al. 1989) that the population of CCK-like cells is heterogenous. PMID- 1917571 TI - A comparison of two populations of decidual cells by immunocytochemistry and prostaglandin production. AB - The decidua has been implicated in the control of human labour, particularly through changes in prostaglandin production, but this tissue contains a number of different cell types. A density gradient system was used to obtain two populations of cells from term human decidua, and these populations were characterised. The more dense cells (population B) was a mixed population, predominantly macrophages (80%), but small numbers of T- and B-lymphocytes were also present, as identified by immunocytochemistry. Most of these cell types also contained detectable levels of cyclooxygenase enzyme. The less-dense cell population (population A) did not contain significant numbers of the above cell types and released prolactin, suggesting that they were decidual stromal cells. This preparation of decidual stromal cells may be of use in defining the functions of these cells in labour. PMID- 1917572 TI - Detection of estrogen receptor (ER) in the rat brain using rat anti-ER monoclonal IgG with the unlabeled antibody method. AB - Application of Sternberger's unlabeled antibody enzyme method for detection of the estrogen receptor (ER) using a rat primary antibody with rat tissues has been discouraged, presumably because nonspecific staining of endogenous IgG was expected with the required anti-rat IgG bridging antibody. Because the blood brain barrier greatly reduces immunoglobulin infiltration into the brain, we hypothesized that rat brain tissue could be specifically immunostained using rat IgG primary antibodies. A rat monoclonal anti-ER antibody (H222) specifically stained ERs in the brains of ovariectomized but not in ovariectomized estrogen treated rats. In contrast, the uterus, a well-perfused target organ stained intensely in a nonspecific fashion. Dense populations of estrogen receptors were observed in the medial preoptic area, the bed nucleus of the stria terminalis, and the arcuate and ventromedial nuclei of the hypothalamus. A monoclonal rat IgG directed against alpha-tubulin labeled primarily cortical dendrites quite distinct from the neuronal nuclei that are the primary antigenic sites for the estrogen receptor antibody. These results confirm that the sensitive unlabeled antibody method can be applied to rat brain tissues, even when the primary antibody is rat IgG and that labeling of endogenous IgG may be used as a simple method to evaluate the integrity of the blood brain barrier. PMID- 1917573 TI - Immunohistological detection of Saruplase (recombinant single-chain urokinase type plasminogen activator) in normal rat tissue. AB - Saruplase--a recombinant single-chain urokinase-type plasminogen activator was identified immunohistochemically in normal rat tissue after intravenous administration by means of a polyclonal antibody. For this purpose, rat tissues were fixed in various ways (liquid nitrogen, ethanol, formaldehyd solution). Saruplase could be detected by the PAP method, streptavidinbiotin system and indirect immunofluorescence in the kidney (proximal tubule), liver (hepatocytes, Kupffer cells) and spleen (reticular cells). Saruplase was not localized in the rat endothelium. It is discussed that the rat-specific receptors for urokinase type plasminogen activator on endothelial cells cannot bind Saruplase due to the extreme species specificity. PMID- 1917574 TI - Fixation of cryo-sections under HIV-1 inactivating conditions: integrity of antigen binding sites and cell surface antigens. AB - Cryostat-sections of biopsies from HIV-infected patients or HIV/SIV-infected experimental animals pose a biohazard risk to laboratory workers. The objective of this study was to select a procedure that appropriately fixes cryo-sections and reduces the risk of HIV-1 infectivity. This inactivation procedure should preserve antigen binding capacity of host-produced antibodies and the antigenic structure of epitopes present in these tissues, while retaining sufficient morphologic detail. We tested the effect of seven different established fixation inactivation procedures for HIV-1 on the detection of specific antibodies and membrane markers, compared to acetone fixation as a reference. Frozen sections of spleens from mice immunized with trinitrophenyl (TNP)-Ficoll were incubated with TNP-alkaline phosphatase to detect specific antibody-forming cells and follicular immune complexes containing TNP-specific antibodies. In addition, sections were stained with monoclonal antibodies directed against IgM (187-1), T-cells (anti Thy-1), and marginal metallophilic macrophages (MOMA-1). Five procedures proved useful as they gave results similar to regular acetone fixation. In contrast, two procedures with a methanol-containing fixative obscured both antigen binding sites and membrane antigens. Subsequently, these five selected procedures were tested on glass slide preparations of HIV-1 infected cell lines, expressing HIV-1 determinants defined by monoclonal antibodies. Finally, the procedures were tested on sections of an HIV-1 infected human lymph node, for detection of HIV specific B-cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917575 TI - Presence of IGF-1-like peptides in the neuroendocrine system of the Atlantic hagfish, Myxine glutinosa (Cyclostomata): evidence derived by chromatography, radioimmunoassay and immunohistochemistry. AB - By the use of radioimmunoassay and chromatography peptides related to insulin like growth factor 1 (IGF-1) have been identified in the cylostomian species Myxine glutinosa. IGF-1-like-immunoreactivity was detected in serum as well as in brain, intestine, pancreas and liver. After acid gel chromatography, the IGF-1 like immunoreactivity eluted as one major peak, with an apparent molecular weight of between 2-4 kDa. When the same antiserum was applied immunohistochemically, IGF-1-like-immunoreactivity was observed in endocrine cells of the mucosal epithelium throughout the primitive intestinal tube. These cells were of the open type and occurred in small clusters. In addition, the majority of the endocrine cells of the pancreas of Myxine displayed IGF-1-like-immunoreactivity. In some of the specimens investigated IGF-1-like-immunoreactive perikarya and fibers were observed on all levels of the brain. Distribution patterns and densities of the IGF-1-like-immunoreactive structures in Myxine correlated with the measurements obtained by radioimmunoassay. Absorption studies with insulin- and IGF-related peptides as well as with crude extracts and the peak material obtained after gel chromatography indicated that the IGF-1-like peptides in Myxine are different from mammalian and non-mammalian insulins as well as from mammalian IGF-1. Generally, the results suggest a long phylogenetic history of IGF-1-like peptides and indicate their fundamental functional impact in all vertebrates. PMID- 1917576 TI - Synaptic relationships between GABA-immunoreactive neurons and an identified uniglomerular projection neuron in the antennal lobe of Periplaneta americana: a double-labeling electron microscopic study. AB - Two types of central neurons in the antennal lobe of the American cockroach Periplaneta americana were labeled with a combination of two specific markers. Their synaptic contacts were characterized and their distribution on the neurons examined. A uniglomerular pheromone-sensitive projection neuron with dendritic arbor in the male-specific macroglomerulus (attractant neuron) was characterized physiologically by intracellular recording and then filled with biocytin, which was converted to a marker for this individual neuron by a preembedding procedure. In a postembedding procedure local, multiglomerular interneurons were marked by immunogold labeling of GABA. Two kinds of synaptic contacts were found on the attractant neuron. (i) Input synapses from GABA-immunoreactive profiles. There were many of these, which (together with results of previous studies) suggests that local interneurons mediate polysynaptic transmission from antennal receptor fibers to the projection neuron. (ii) Output synapses onto GABA-immunoreactive profiles and onto non-identified neurons. These contacts indicate that signals generated by the projection neurons in a given glomerulus are passed back to multiglomerular interneurons and hence are also transmitted to other glomeruli. PMID- 1917577 TI - Identification of muramyl derivatives in Mollusca Gastropoda tissue. AB - Previous findings have demonstrated the presence of muramic acid and the lack of sialic acid in gastropod glycoconjugates from different tissues. The present study investigated the composition of muramyl derivatives in Mollusca Gastropoda tissue from the foot, mantle and periesophageal ganglia, using HRP-labeled lectins (LTA, UEA I, GSA IB4, GSA II, DBA, SBA, RCA II, WGA, PNA, ConA) and glycosidase digestion (neuraminidase, lysozyme, alpha-L-fucosidase, beta-N acetylglucosaminidase, alpha-N-acetylgalactosaminidase). Muramyl derivatives from the tissue examined showed some differences related to the composition of the terminal disaccharides. Indeed, foot and mantle mucocytes exhibited muramic acid in a terminal position, linked to (subterminal) N-acetylgalactosamine, whereas in neuron cells muramic acid was present in an internal position and linked to N acetylglucosamine. Diversities also occurred between foot and mantle mucocytes with respect to the receptor sugar for penultimate N-acetylgalactosamine. PMID- 1917579 TI - Quantitative succinate dehydrogenase analysis in normal and ragged-red muscle fibers. AB - Single fiber analyses were performed in normal and diseased muscle by means of a high-resolution microphotometric method. We investigated the activity distribution of a mitochondrial marker enzyme, succinate dehydrogenase, within single muscle fibers. We differentiated between the central and the subsarcolemmal region. Both normal muscle fibers, and ragged-red fibers from patients with a mitochondrial myopathy showed significantly higher succinate dehydrogenase activities in the subsarcolemmal region. Since the fibers' supply of oxygen is accomplished by diffusion from capillaries located close to the sarcoplasmic membrane our results are of functional importance. PMID- 1917578 TI - The kallikrein-kinin system in the rat hypothalamus. Immunohistochemical localization of high molecular weight kininogen and T kininogen in different neuronal systems. AB - High molecular weight kininogen (HKg) and T kininogen (TKg) were detected and localized by immunocytochemistry in adult rat hypothalamus. In addition, kininogens were measured by their direct radioimmunoassay (RIA) or by indirect estimation of kinins released after trypsin hydrolysis and high pressure liquid chromatography (HPLC) separation of bradykinin (BK) and T kinin. A specific HKg immunoreactivity demonstrated with antibodies directed against the light chain (LC) of HKg was colocated with SRIF in neurons of hypothalamic periventricular area (PVA) projecting to external zone (ZE) of median eminence (ME). Heavy chain (HC) immunoreactivity which could be related to HKg or to low molecular weight kininogen (LKg) was detected in some other systems: i) parvocellular neurons of suprachiasmatic (SCN) and arcuate nuclei containing SRIF, ii) magnocellular neurons (mostly oxytocinergic) of paraventricular (PVN) and supraoptic (SON) nuclei, iii) neurons of dorsomedian and lateral hypothalamic areas. TKg immunostaining was restricted to magnocellular neurons of PVN, SON, accessory nuclei (mostly vasopressinergic) and to parvocellular neurons of SCN (vasopressinergic). TKg projections are directed towards the internal zone (ZI) of ME, but very few immunoreactive terminals are detectable in neurohypophysis. TKg staining parallels with vasopressin during water deprivation, and is undetectable in homozygous Brattleboro rats. In some magnocellular neurons, TKg and HC (related to HKg or LKg) are coexpressed. TKg, was also detected in hypothalamus and cerebellum extracts by direct RIA, and BK and T kinin were identified after trypsin hydrolysis. HKg and LKg can act as precursor of BK which can play a physiological role as releasing factor, neuromodulator- neurotransmitter,--or modulator of local microcirculation in hypothalamus. The three kininogens are also potent thiolprotease inhibitors which could modulate both the maturation processes of peptidic hormones and their inactivation and catabolism. PMID- 1917580 TI - Are there cholinergic through-fibers in the superior cervical ganglion of the mouse? AB - Choline acetyltransferase immunocytochemistry was used to detect the presence and distribution of cholinergic through-fibers in the superior cervical ganglion of adult mice. The results revealed a great number of choline acetyltransferase positive axons in the cervical sympathetic trunk and the varicose terminal axons involved in the innervation of the principal ganglionic cells within the ganglion. Immunostained axons were scarce or absent in the external or internal carotid nerves. The immunocytochemical results argue against the physiological importance of cholinergic through-fibers in the postganglionic nerves. PMID- 1917581 TI - Demonstration of glial fibrillary acidic (GFA) protein by electron immunocytochemistry in the granular cells of a choristoma of the neurohypophysis. AB - The origin of the nests of granular cells comprising choristomas of the infundibular process and the stalk of the pituitary gland is controversial. Using electron microscopic immunocytochemistry, the astrocytic marker, glial fibrillary acid protein (GFAP), has been demonstrated diffusely in the cytoplasm of some of the granular cells, but not within the granules or cellular organelles of some of the granular cells. Cytoplasmic filaments were not detected in these granular cells, but cells with abundant filaments extended processes between the granular cells. These filament-rich cells stained much more intensely for GFAP than the positively staining granular cells. The expression of GFAP by the granular cells and the filament-containing cells between them in the pituitary implies an astrocytic origin for both cell types, but the absence of filaments in the granular cells suggests that the GFAP is in an unpolymerized (soluble) form. The granular cell is likely to represent a transitional cell type of astrocytic origin in which the glial filaments have undergone partial or complete degradation. PMID- 1917582 TI - Changes in the distribution of intermediate filament proteins and collagen IV in fetal and adult human pancreas. I. Localization of cytokeratin polypeptides. AB - The expression patterns of individual cytokeratin polypeptides in foetal and adult human pancreatic tissues were examined using monoclonal antibodies. We demonstrated that human pancreatic epithelia in early stages of development (14 weeks of gestation) contain cytokeratins 7, 8, 18 and 19, which are typical of simple epithelia, as well as cytokeratin 4 and 17, which are characteristic of stratified epithelia. In the pancreatic ducts, most of these cytokeratins appeared to be expressed together. Cytokeratins 1, 5, 10, 13, 16 and 20 were not detectable. In contrast, the pancreatic parenchyma was only positive for cytokeratins 8 and 18, except a transient expression of cytokeratins 7 and 19 in pancreatic islets and acinar cells during the foetal development. A focal cytokeratin 7 staining of single acinar cells was seen in newborn and in adult islets. In the stromal tissue, vascular smooth muscle cells were partly reactive with cytokeratin 8 and 18 specific antibodies. The results are discussed in the light of differentiation-dependent changes in the expression of individual cytokeratin polypeptides in developing epithelia. PMID- 1917584 TI - [Technique and complications of microvascular reanastomosis]. AB - We describe 193 free tissue transfers for routine indications and for the solution of difficult problems. Some complex venous anastomoses are illustrated. The complete loss of a transplant is the most important complication of free tissue transfer. In most cases it is due to a thrombosis of the venous microanastomosis. PMID- 1917583 TI - [Jejunum transplantation. Therapeutic progress?]. AB - Either the musculocutaneous island flap (especially the pectoralis major flap) or the free jejunal transplant are used for large mucosal defects of the oro- and hypopharynx. As a jejunal transplant is more time consuming than the use of a musculocutaneous flap, its use must be justified. A review of the literature and our own experience show that the jejunal transplant should be preferred because (1) it is more versatile, (2) it can easily be handled, (3) it provides better functional results, (4) it avoids the functional and aesthetic morbidity of the donor site defect and (5) it has a lower complication rate than the pectoralis major flap. PMID- 1917585 TI - [Clinical use of microvascular reanastomosed transplants]. AB - We report 155 free jejunal transplants carried out since August 1984. The complications and the indications for the use of free intestinal transplants in the reconstruction of defects of the oral cavity and pharynx are recorded. Also we report the use of the revascularised latissimus dorsi myocutaneous flap and the fascicutaneous radial forearm flap in head and neck reconstruction. PMID- 1917587 TI - [Mandibular resection in cancer of the tongue and/or mouth floor]. AB - The role of the lingual periosteum in the spread of tumours is not yet clear. We examined the histological behaviour of 60 cancers of the tongue and floor of the mouth lying close to the mandible. There were no tumour cells in the periosteal lymphatics. This is in accord with clinical experience that tumour invasion of the periosteum is not associated with an increased rate of metastases to the cervical lymph nodes. From our experience, we conclude that (1) a radical resection of the mandible is mandatory for every lesion lying in the gingivo lingual gutter that invades bone; (2) for tumours close to, but not directly invading the lingual surface of the mandible, marginal resection of the alveolar ridge is appropriate and provides an adequate margin. PMID- 1917586 TI - [Modification of the microvascular reanastomosed latissimus dorsi flap for reconstruction after extensive maxillary resection]. AB - Large defects after extended maxillectomy and orbital exenteration were immediately reconstructed using a modification of the revascularized musculocutaneous latissimus dorsi flap. Three skin islands were transplanted based on the muscular part of the flap. The first island replaced the hard palate, the second the lateral nasal wall and the third was used together with the preserved eyelids to reconstruct an eye socket. The muscular part of the flap was folded spirally so that each skin island reached the site to be reconstructed. PMID- 1917588 TI - [Oral hygiene and dental status in patients with squamous cell cancers of the upper aerodigestive tract]. AB - Dental status and oral hygiene were investigated in a case-control study of 100 patients suffering from head and neck cancer and 214 age- and sex-matched controls. The dental status and paradontal status are poor in cancer patients. The number of decayed or missing teeth was significantly higher in our patients compared with controls. Furthermore, in the tumour group the rate of moderate or severe gingivitis and the presence of extensive tartar were significantly higher. These findings are mainly due to poor oral hygiene. Few of the cancer patients ever brushed their teeth, and the number of dental check-ups was significantly lower than in control subjects. Poor oral hygiene is predominantly an expression of self-neglect due to chronic alcohol consumption, which was present in nearly all of our patients. Furthermore, it seems to be related to an unsatisfactory health education in the lower social strata, to which most of cancer patients belong. PMID- 1917589 TI - [Indications for transnasal endoscopic and microscopic and external paranasal sinus operations. A critical intermediate report]. AB - A comparison of the paranasal sinus operations performed in 1980/1981 (n = 310) and 1988/1989 (n = 540) in the author's clinic demonstrates an impressive shift to endonasal techniques. These operations have increased from 35.4% to 74.6%. About three-quarters of the operations for chronic sinusitis were done by the endoscopic technique. In a quarter of the cases we found an extremely extensive chronic recurring polyposis indicating systemic disease. We prefer the microscopic technique for these cases. The extranasal approaches are now used more rarely in the surgery of inflammatory lesions. Nevertheless, they are still important for the treatment of complications, injuries and tumours of the paranasal sinuses, and they constitute 18.9% of all operations. PMID- 1917590 TI - [Retrotonsillar abscess. Diagnosis by flexible endosonography]. AB - A retrotonsillar abscess is a dangerous complication of acute tonsillitis that can be fatal if treatment is delayed. We report the pre-operative findings of flexible endosonography and transcutaneous sonography of a patient with retrotonsillar abscess. The results show, that the new digitally guided, flexible probes of endosonography improve the diagnosis of paratonsillar abscess and are superior to transcutaneous sonography especially for delineating retrotonsillar spread. PMID- 1917591 TI - HLA antigens influence resistance to lung carcinoma. AB - The concept of genetic factors playing a role in the pathogenesis of lung cancer has gained increased attention. The present study was undertaken to reexamine the question of HLA antigen association with carcinoma of the lung. In a study of 90 patients, a significant association occurred between HLA-DR7 and resistance to lung cancer, after accounting for smoking status and sex. HLA class I antigens were also implicated. These results suggest that major histocompatibility complex loci affect carcinoma of the lung. PMID- 1917592 TI - Autoimmunity in human immunology. PMID- 1917594 TI - The American Society for Histocompatibility and Immunogenetics, 17th annual meeting. October 11-15, 1991, Washington, DC. Abstracts. PMID- 1917593 TI - Autocrine stimulation of interleukin 1 in human adherent synovial lining cells: down regulation by interferon gamma. AB - Interleukin 1 (IL-1) exerts biological properties on various immune and nonimmune cell types and tissues and thus may play an important role during chronic inflammatory processes. Here we have examined the IL-1 biosynthesis in adherent synovial lining cell (ASLC) cultures obtained from patients with rheumatoid arthritis (RA). We report that ASLCs in culture showed heterogeneous endogenous levels of IL-1 alpha and beta expression. Recombinant interleukin 1 (rIL-1) alpha or beta induced increases of IL-1 alpha and beta mRNA and proteins levels in ASLCs. Although IL-1 synthesis is enhanced by rIL-1 treatment, no soluble IL-1 alpha or beta could be detected by specific enzyme-linked immunosorbent assays. A pretreatment with recombinant IFN gamma (rIFN gamma) down-regulated the effect of rIL-1 on IL-1 synthesis in ASLCs. Actinomycin D suppressed the endogeneous and rIL-1-induced IL-1 mRNA expression Indomethacin, in the presence of rIL-1 alpha or beta, up-regulates the level of expression of IL-1 beta in ASLCs pretreated with rIFN gamma, but has the opposite effect in non-pretreated cells. The increase of IL-1 gene expression by rIL-1 in human ASLCs from RA patients may contribute as an amplification of the disease progress. These studies may also explain the beneficial effects of IFN gamma in experimental models of IL-1 induced bone and cartilage degradation and in patients with diseases involving IL 1. PMID- 1917595 TI - Pions--the potential for therapeutic gain in locally advanced prostate cancer: dose escalation and toxicity studies. AB - Since 1982, 49 patients with locally advanced carcinoma of the prostate have been treated with pion radiotherapy in tolerance and tumor response studies. The relative biological effectiveness (RBE) was confirmed as 1.5 for both acute and late effects, a figure expected on the basis of animal and human studies. The radiation dose has been safely escalated to tolerance, which is estimated to be 37.5 Gy pi in 15 fractions (volume less than 500 cc), and 36 Gy pi in 15 fractions (volume 500-800 cc). Severe acute toxicity occurred in 6% and severe chronic toxicity in 4%, figures comparable to those seen with conventional radiotherapy. The equivalent photon doses are approximately 78 Gy in 39 fractions and 73 Gy in 36 fractions, respectively. That this high dose can be delivered with no increase in toxicity is a reflection of smaller volume radiotherapy achieved by exploiting the dose distribution and biological characteristics of pions. Local response rates of 94% are reported. A Phase III study is now under way. PMID- 1917596 TI - Twice-daily, split-course abdominopelvic radiation therapy after chemotherapy and positive second-look laparotomy for epithelial ovarian carcinoma. AB - Between July 1983 and December 1988, 34 patients with ovarian carcinoma received whole abdominal irradiation in an attempt to eliminate residual disease following second-look laparotomy. Three additional patients who had initial complete responses to chemotherapy were treated for a recurrence of their disease. All patients had been treated with chemotherapy that included cisplatin and cyclophosphamide. Three patients had also received doxorubicin with some or all chemotherapy cycles. Thirty Gray of abdominopelvic radiation therapy (APRT) was delivered using a twice-daily, split-course schedule. Eleven patients also had a boost of 9-20 Gy to sites of residual disease. Treatment was well tolerated. Only one patient did not complete therapy and two patients had 1-week prolongations of treatment because of hematologic toxicity. Thirty-two percent of patients had grade 2 neoplasms and 61% had grade 3 disease. Three patients with grade 1 tumors continue to have no evidence of disease 20-50 months after irradiation. Patients with grade 2 and 3 neoplasms who had microscopic residual disease prior to APRT had relapse-free survival rates at 3-years of 10% and 14%, respectively. Twelve patients with gross residual disease had rapid recurrences (median time to relapse, 4.9 months) and all have died of their disease. Although 14 patients (38%) have experienced small bowel obstructions, all of these had known recurrent abdominal disease at the time. Twenty patients (54%) had undergone more than two abdominal surgeries prior to APRT, and several were noted to have extensive adhesions at second-look laparotomy. None of the five patients currently believed to be free of disease has experienced a small bowel obstruction. Radiation is only one of several factors that contributed to bowel obstructions. Although APRT may be able to eliminate residual disease in a small proportion of patients with microscopic residual disease after chemotherapy, the aggressive biology of tumors that respond incompletely to chemotherapy and the compromises in radiation dose and schedule that must be made in these heavily treated patients probably contribute to the disappointing results of this treatment. PMID- 1917598 TI - Survival and failure analysis in stage II endometrial cancer using the revised 1988 FIGO staging system. AB - Fifty-one patients with Stage II endometrial carcinoma diagnosed between 1974 and 1987 were restaged according to the FIGO 1988 revisions for endometrial carcinoma. Patients were divided into Stage IIA, those patients with cervical glandular involvement without stromal invasion, and Stage IIB, those patients having stromal invasion of the cervix. Tumor grade was also assessed. Patients were treated with radiation therapy alone, pre-operative radiation therapy followed by a simple hysterectomy, or a simple hysterectomy followed by postoperative radiation therapy. The 5-year actuarial survival for Stage IIA was 86% and the 5-year actuarial survival for Stage IIB was 46% (p = 0.06). The 5 year local recurrence rate in each group was 9%. Stage IIA had a distant metastases rate of 14% whereas 44% of the patients in Stage IIB developed distant disease (p = 0.06) at 5 years. The grade of the tumor did not play a role in local recurrence. However, when tumor grade was analyzed with respect to distant disease, 14% of patients with grade 1 tumors developed distant metastases, 31% of patients with grade 2 tumors developed distant metastases, and most significantly, 63% of patients with grade 3 tumors developed distant metastases (p = 0.004). There was no statistically significant relationship between stromal invasion and tumor grade. This study concludes that grade is the greatest predictor of survival, with only 37% of grade 3 patients surviving at 5 years. As a predictor of survival, stromal invasion is of less significance than grade (p = 0.06 vs. p = 0.004). Death most often occurs because of distant metastases, and local failure is rare and is not dependent on the degree of cervical involvement or grade. PMID- 1917597 TI - Adjuvant whole abdominopelvic irradiation for high risk endometrial carcinoma. AB - Fifty-six patients with surgical Stage III or IV endometrial carcinoma, or earlier stage disease with two or more risk factors for peritoneal recurrence, were given postoperative whole abdomino-pelvic irradiation (WAPI) with nodal and vaginal boosts between November 1981 and May 1989. Mean age at diagnosis was 63 years. Twenty-seven patients were surgical Stage I-II, 17 Stage III, and 12 Stage IV. Thirty-seven (66%) had deep myometrial involvement, 34 (61%) had positive peritoneal cytology, 31 (55%) had high grade lesions, 20 (36%) had either serous papillary or adenosquamous histologic variants, and 13 (23%) had up to 2 cm residual disease remaining after surgery. Mean overall follow-up was 45 months. The 7-year actuarial survival was 63.8% with a 7-year disease-free survival (DFS) of 60.9%. By surgical stage, the 7-year DSF was 77.1% for Stage I-II, 57.8% for Stage III, and 25.0% for Stage IV (p = 0.006). The 7-year DSF was 79.8% for those with lesions of Broder's grade 1 or 2, and 46.9% for grades 3 or 4 (p = 0.001). Multivariate analysis demonstrated that of all covariates considered, only surgical stage and histologic grade had prognostic significance for survival and disease-free survival. Acute toxicity has been common but mild; chronic toxicity has been almost entirely subclinical with the exception of three cases of moderate to severe bowel toxicity. These results suggest that post-operative WAPI is a safe and efficacious treatment alternative for patients with surgical Stage I through III high-risk endometrial carcinoma. PMID- 1917599 TI - Flow cytometric DNA content analysis of paraffin block embedded endometrial carcinomas. AB - Flow cytometry is being used as an aid in planning the treatment of patients with various malignancies. We report our experience with DNA content analysis on paraffin-embedded carcinomas. Hospital, radiation therapy, clinic, and pathology records were reviewed in 139 cases of endometrial carcinoma diagnosed between December 1980 and December 1986. Patients having Stage IV tumors, endometrial sarcomas, dual primary tumors, or incomplete records were eliminated from the analysis, which left 98 evaluable patients. This report outlines our experience with the first 20 patients. Five of 20 (25%) specimens demonstrated DNA content consistent with aneuploidy, median coefficient of variance of 5.3%. The median survival time of these five patients is 55 months, with three dying of cancer and one patient dying of other causes but with metastatic disease. The median %S phase was 3.7% in the 15 patients comprising the DNA content diploid population, median coefficient of variance 5.4%. No patient whose tumor showed S-phase cells below 3.7% died of endometrial cancer. Four of 7 patients developed recurrent cancer with 3 of the 4 patients dying of disease in the high %S phase group. The median patients survival time in the DNA content diploid population was 73 (range: 17-98) months. Patients with 3.7% or below S-phase cells had a median survival time of 75 (range: 40-98) months whereas the median survival time was 48 (range: 17-89) months for patients having a %S phase fraction above 3.7%. Although the number of patients studied is small, it appears that DNA content aneuploid tumors are frequently "upstaged" at surgery. These patients may not benefit from preoperative irradiation. Accurate determination of the %S phase fraction in DNA content diploid tumors may possibly identify patients with a poorer prognosis who may benefit from adjuvant therapy. PMID- 1917600 TI - Results of radiotherapeutic management of primary carcinoma of the vagina. AB - Forty-five previously untreated patients with primary carcinoma of the vagina were treated with curative radiotherapy from 1965 through 1985. All patients were staged according to the FIGO system. One patient was classified as Stage 0, 15 as Stage I, 22 as Stage II, 6 as Stage III, and 1 as Stage IV. Treatment consisted of intracavitary irradiation alone in Stage 0 patients. Stage I patients received intracavitary/interstitial irradiation alone or in combination with external irradiation and an implant when feasible. When treated with an implant only, the total tumor dose delivered was between 65-70 Gy. External irradiation consisted of delivering a dose of 45-50 Gy over a period of 4 1/2-5 weeks to the whole pelvis to treat the regional lymph nodes. An additional dose of 20-25 Gy was delivered to the site of original involvement using an implant when feasible. If not technically feasible, as in advanced stages, the patient was treated with additional external irradiation to a total dose of 65-70 Gy by a shrinking field technique. All patients except one were followed either until death or for a minimum of 2 years. The actuarial 5-year survival rates were 100% for Stage 0, 78% for Stage I, and 71% for Stage II patients. None of the patients with Stage III or IV disease survived. Of the patients who recurred, all but two did so within 16 months after diagnosis. Pelvic recurrence as the first site of recurrence occurred in 86% of the patients who recurred. Distant recurrence as a component occurred in 20% of all failures. Complications as a consequence of therapy occurred in 18% of the patients. Vaginal necrosis that healed with conservative treatment was seen in four patients and the other four patients had rectal complications of varying severity. Thus, curative radiotherapy is an effective method of treatment, with acceptable morbidity, in patients with early stage primary carcinoma of the vagina. PMID- 1917601 TI - Design of a plastic minicolpostat applicator with shields. AB - A plastic intracavitary applicator system for the treatment of cancer of the uterine cervix is described. This applicator has a minicolpostat and a mechanism for affixing the tandem to the colpostats. Traditional afterloading refers only to the radioactive source. Both the source and the ovoid shield are afterloaded together in this applicator in contrast to traditional afterloading systems which afterload the source alone. A potential advantage of our applicator system is that it allows high quality CT localization because the sources and shields can be removed and the applicator is made of plastic. The advantages and disadvantages of this variation to the Fletcher system as well as other aspects of applicator design are discussed. An experimentally verified dose calculation method for shielded sources is applied to the design problems associated with this applicator. The dose distribution calculated for a source-shield configuration of the plastic applicator is compared to that obtained with a commercial Fletcher-Suit-Delclos (FSD) applicator. Significant shielding improvements can be achieved for the smallest diameter ovoid, that is, in the minicolpostat. The plastic minicolpostat dose distributions are similar to those produced by the conventional larger diameter colpostats. In particular, the colpostat shielding for rectum and bladder, which is reduced in the metal applicator's minicolpostat configuration, is maintained for the plastic minicolpostat. Further, it is shown that, if desired, relative to the FSD minicolpostat, the mucosa dose can be reduced by a suitable change of the minicolpostat source position. PMID- 1917603 TI - Nucletron MicroSelectron calibration and radiation survey. AB - The calibration of a Nucletron MicroSelectron High Dose Rate Remote Afterloader unit and the radiation survey around the facility is discussed. The radiation survey of the facility indicates that the use of an existing linear accelerator vault will provide adequate shielding. The methodologies for performing source calibration are presented. PMID- 1917602 TI - A rapid-afterloading vaginal cylinder for 137Cs brachytherapy. AB - A small diameter, single-step afterloading vaginal cylinder has been developed for 137Cs brachytherapy of the vaginal cuff and walls. The Lucite cylinder has an interior slot of rectangular cross section running along its length and opening to the outside of the patient. A single rectangular Lucite insert, containing preselected sources, fits into the slot. Two short sources in the tip form a T with the sources along the vaginal canal and provide a high, uniform dose rate across the spherical tip of the applicator. A catalog of 30 precalculated loadings provides surface dose rates at the tip which vary from 140 to 230 cGy/hr for standard source strengths, as well as a variety of dose rate profiles along the vaginal wall. The applicator is tapered at the base for comfortable and secure placement, and the single-step insertion reduces both patient discomfort and personnel radiation exposure for this procedure. PMID- 1917604 TI - Evaluation of a total scalp electron irradiation technique. AB - A dosimetric evaluation of a total scalp electron-beam irradiation technique that uses six stationary fields was performed. The initial treatment plan specified a) that there be a 3-mm gap between abutted fields and b) that the field junctions be shifted 1 cm after 50% of the prescribed dose had been delivered. Dosimetric measurements were made at the scalp surface, scalp-skull interface, and the skull brain interface in an anthropomorphic head phantom using both film and thermoluminescent dosimeters (TLD-100). The measurements showed that the initial technique yields areas of increased and decreased dose ranging from -50% to +70% in the region of the field junctions. To reduce regions of nonuniform dose, the treatment protocol was changed by eliminating the gap between the coronal borders of abutted fields and by increasing the field shift from 1 cm to 2 cm for all borders. Subsequent measurements showed that these changes in treatment protocol resulted in a significantly more uniform dose to the scalp and decreased variation of doses near field junctions (-10% to +50%). PMID- 1917605 TI - Expedient set-up of tangential breast fields with a simple gantry attachment. AB - A novel technique for setting up tangential fields is described. The technique uses a simple device (Breast Aligner) which attaches to the collimator of the treatment unit. The function of the Breast Aligner is similar to conventional front and back pointers except that the beam edge rather than central ray is defined. By delineating beam entrance and exit points at the posterior field edge, the device greatly simplifies and expedites set-up, and enhances precision of port alignment. Additional advantageous features include: (a) the ability to compensate for small inadvertent variations from the initial set-up position or for patient movement between the set-up of opposing ports, (b) the ability to visually check port alignment in the treatment position immediately before irradiation, and (c) decreased chance of human and equipment error by eliminating the need for measurements and calculations at the time of treatment. Our method can be used for SSD or SAD techniques and, with minor adjustment, is applicable for establishment of coplanar cephalad field borders as required at the junction of a supraclavicular field. PMID- 1917606 TI - The relationship between facility structure and outcome in cancer of the prostate and uterine cervix. AB - Since 1972, the Patterns of Care Study (PCS) has investigated the quality and demographics of clinical radiation therapy in the United States. Using outcome results from a study of patients treated for carcinoma of the cervix or adenocarcinoma of the prostate in 1978, an evaluation of the relationship of outcome to facility structure was undertaken. Binary logistic regression of outcome on stage and structure showed consistent but modest contributions of structure, even after the effects of stage were considered. Implications of these findings are discussed. PMID- 1917607 TI - Cancer of the uterus: the value of MRI pre- and post-irradiation. AB - In cancer of the uterus, the morphologic factors influencing the choice of therapy and patient prognosis are tumor size, depth of invasion, presence of lymph node metastasis, and stage. Clinical staging is often inaccurate with resultant suboptimal therapy, thereby invalidating comparison between treatment options. The available cross-sectional imaging modalities of ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI), have significantly improved the staging of malignant disease. In the pelvis, MRI offers several advantages over the other imaging modalities. In particular, MRI has excellent soft tissue contrast resolution, allowing direct multiplanar imaging with evaluation of tumor extension in all three directions, and has variable imaging parameters (TR/TE)--characteristics of the echo patterns--to facilitate optimal tumor detection. It is a non-invasive technique with an ability to visualize blood vessels without the need for contrast injection and is independent of body habitus. However, MRI is not tissue-specific and a histological diagnosis is required in all cases. In the post-radiotherapy patient, MRI has the ability to demonstrate radiation tissue change and the potential to differentiate radiation fibrosis from recurrent/residual tumor. Its non-invasive nature and lack of ionizing radiation make it suitable for assessing treatment response and as an adjunct for patient monitoring. PMID- 1917608 TI - The vanishing role of preoperative radiation therapy for stage I endometrial carcinoma. PMID- 1917609 TI - The effect of overall treatment time in radiotherapy for localized prostate carcinoma. PMID- 1917611 TI - 3-D beams need unambiguous 3-D names. PMID- 1917610 TI - Outcome for lymph node dissection negative T-1b, T-2 (A-2,B) prostate cancer treated with external beam radiation therapy in RTOG 77-06. AB - One hundred four patients with stage T-1b, T-2 N-O M-O prostate cancer were treated with external beam irradiation as part of RTOG 77-06. Lymph nodes were negative by lymph node dissection in 16 patients with T-1b and 88 patients with T 2 cancers. Survival exceeds age matched expected survival for the 10 years of observation (63% vs 59% at 10 years). Patterns of failure at 10 years show 87% of patients were free of isolated local recurrence, 79% free of metastatic failure, 67% free of any failure, and cause specific survival shows 86% free of cancer death at 10 years. The outcome of this group is equal or superior to reports of radical prostatectomy in similar stage patients. PMID- 1917612 TI - Exact calculation of isodoses with the Leksell Gamma Unit. PMID- 1917613 TI - The use of intraoperative transabdominal ultrasound in gynecologic brachytherapy. PMID- 1917614 TI - Electron beam irradiation of conjunctival lymphomas. PMID- 1917615 TI - Cell repopulation and overall treatment time. PMID- 1917616 TI - Impact of dose in outcome of irradiation alone in carcinoma of the uterine cervix: analysis of two different methods. AB - This is a retrospective analysis of 1211 patients with histologically proven invasive carcinoma of the uterine cervix with a minimum follow-up of 3 years treated with irradiation alone. The pelvic failure rates by stage were 9.6% for IB, 18.6% for IIA, 23% for IIB, 41% for III, and 75% for Stage IVA disease. External beam and intracavitary irradiation doses to point A and pelvic lymph nodes were calculated. In patients with Stage IB and IIA disease there was no significant correlation between doses to these points and pelvic tumor control. In Stage IIB doses of less than 6000 cGy to point A correlated with a high pelvic failure rate (8 of 12, 66.7%) in contrast to doses of 6000 to 9000 cGy (61 of 261, 23.4%) or higher than 9000 cGy (10 of 74, 13.5%) (p less than or equal to 0.01). In Stage III the pelvic failure rate with doses below 6000 cGy to point A was 72% (18 of 25) compared to 39% (71 of 180) for 6000 to 9000 cGy or 35% (27 of 77) with doses above 9000 cGy (p less than or equal to 0.01). TDF calculation of doses was carried out. In Stage IB and IIA there was no significant correlation between TDF to point A and probability of pelvic recurrence. In Stage IIB with TDF below 135, the pelvic recurrence rate was 41.6% (20 of 48) compared to 20% (61 of 305) with higher TDF (p less than or equal to 0.01). In Stage III the pelvic failure rate was 51% with TDF below 160 (70 of 136) in comparison with 29.5% (46 of 156) with higher TDF (p less than or equal to 0.01). Grade 2 sequelae of therapy were noted in about 10% of the patients and grade 3 in 4.7% of patients with Stage IB (18 of 384), 10.2% (12 of 128) with Stage IIA, 9.3% (33 of 353) with Stage IIB, and 8.2% (24 of 293) with Stage III disease. Doses from external beam and intracavitary irradiation to the rectum or the bladder neck were calculated. The actuarial incidence of major rectal or rectosigmoid sequelae was 2% to 4% with doses to the rectum of 6000 to 8000 cGy, 7% to 8% with 8000 to 9500 cGy, and 13% with doses higher than 9500 cGy (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917617 TI - Stage IB or IIA-B carcinoma of the intact uterine cervix greater than or equal to 6 cm in diameter: is adjuvant extrafascial hysterectomy beneficial? AB - This is an analysis of 150 patients with Stage IB or IIA-B carcinoma of the intact uterine cervix greater than or equal to 6 cm in diameter treated with irradiation alone (75 patients) or irradiation followed by surgery (75 patients) at the University of Florida between October 1964 and June 1983. Minimum follow up in this series was 5 years. There was no significant difference in the distribution of prognostic factors between the two treatment groups. The 5-year local control rate was 74% with irradiation alone and 76% with irradiation and surgery. The 5-year survival rates for irradiation alone versus irradiation plus surgery were as follows: cause specific, 62% and 55%, and absolute, 54% and 52%. The proportion of patients who developed treatment complications necessitating hospitalization or a second operation was 4/75 (5%) after irradiation alone and 12/75 (16%) after irradiation and surgery. The authors conclude that the routine use of adjuvant extrafascial hysterectomy is not warranted in this patient population. PMID- 1917618 TI - The effect of volume of disease in patients with carcinoma of the uterine cervix. AB - This is a retrospective study of 635 consecutively treated patients with FIGO Stage IIB or IIIB carcinoma of the uterine cervix. All patients were treated definitively with radiation therapy. The effect of volume of disease on outcome was studied. The 5-, 10-, and 15-year disease-free survivals (DFS) for the 346 Stage IIB patients were 64%, 61%, and 58%, respectively. Corresponding DFS for the 289 Stage IIIB patients were 40%, 38%, and 34%, respectively. The presence of bilateral parametrial invasion did not alter the 10-year DFS in Stage IIB patients (61% vs 64%, p = 0.60) but did decrease it in Stage IIIB patients (34% vs 50%, p = 0.006). Patients with both Stage IIB and IIIB cancers and central bulky disease (greater than or equal to 5 cm in diameter) had decreased DFS when compared to those without central bulky disease. Stage IIB patients with the lateral half of the parametrium involved had a decreased 10-year DFS in comparison with medial half involvement (52% vs 68%, p = 0.004). The total pelvic failure rate was 23% for Stage IIB and 41% for Stage IIIB patients. Central bulkiness increased the pelvic failure rate by about 11% for all patients. Bilateral parametrial disease increased the pelvic failure rate in Stage IIIB patients but not in patients with Stage IIB disease. The total pelvic failure rate for Stage IIB patients was greater in those whose disease extended into the lateral parametrium. Multivariate analysis was done using stage, lateral pelvic wall dose, parametrial disease, central bulkiness, age, and total dose to point A as variables. With local control as the endpoint, only stage (IIB vs IIIB) was significant (p = 0.008). Using DFS as the endpoint, stage (p = 0.0001) and central bulkiness of tumor (p = 0.026) were significant. Complications were not increased in patients with bulky or bilateral disease. We conclude that there is justification for subdividing FIGO Stage IIIB patients into those with unilateral or bilateral disease; however, these data do not support such a division for FIGO Stage IIB patients. These latter patients would be better analyzed with reference to medial versus lateral parametrial extension because of the difference in pelvic control and survival. PMID- 1917619 TI - Incidence of complications with mini vaginal culpostats in carcinoma of the uterine cervix. AB - Between 1980 and 1987, 298 patients with carcinoma of the uterine cervix were treated at the University of Louisville Department of Radiation Oncology. Of these, 197 (66.1%) were treated for cure by radiotherapy alone: 36 by external beam alone and 161 by external beam and tandem and ovoid applications. The F.I.G.O. staging of the 161 patients was 82 (50.1%) Stage IB, 9 (5.6%) Stage IIA, 40 (24.9%) Stage IIB, and 30 (18.6%) Stage III. The usual treatment was whole pelvis irradiation followed by two intracavitary applications using the Fletcher Suit Applicators of tandem and ovoids in 79/161 patients (49%), a 3-M Mini Applicator (Fletcher Suit Delcos Applicator) in 52/161 patients (32.3%), and a 3 M Mini Applicator with Caps in 30/161 patients (18.6%). The incidence of grade 3 4 gastrointestinal or genitourinary complications as defined by the RTOG was 19.3% (31/161). Various treatment parameters were analyzed to define possible contributing factors. Grade 3-4 complications were seen in 7.6% (6/79) of patients treated with the standard ovoid Fletcher system, 26.9% (14/52) treated with the mini-ovoid system, and 36.6% (11/30) treated with the mini-ovoid system with caps (p = .0006). Although trends were noted, neither the vaginal surface dose (VSD) from the ovoids nor the addition of the external beam dose to the VSD (total vaginal surface dose = TVSD) were significant independent variables (p = 0.19 and = 0.133, respectively). The TVSD was significant when comparisons were made between different ovoid systems (p = 0.05 for less than 12,000 cGy and p = 0.004 for greater than 12,000 cGy). In this study, the 3-M mini applicator was associated with a significant increase in grade 3-4 complications as compared to the Standard Fletcher Suit Applicator. PMID- 1917620 TI - Analysis of complications in patients with endometrial carcinoma receiving adjuvant irradiation. AB - We analyzed the complications in 310 patients with pathologically documented endometrial carcinoma who received adjuvant radiation therapy (RT) at Fox Chase Cancer Center between 1970 and 1986. Variables included timing of treatment, technique, total dose, age, diabetes, previous abdominal surgery, hypertension, prior bowel pathology, and lymphadenectomy. According to the FIGO (1985) system, 258 patients had Stage I disease, 48 had Stage II, and one had Stage III. One hundred seventy patients received preoperative (preop) RT, 138 received postoperative (postop) RT, and 2 received preop and postop RT. A 4-field technique was used for 212 of 235 patients receiving external-beam (EX) RT, and 75 patients were treated with intracavitary (IC) RT only. Median follow-up was 5.5 years. Actuarial survival of all 310 patients was 78% at 5 years. Thirty-two complications occurred, involving the rectum, small bowel, femur, or lower extremity. Complications were graded according to the ECOG scoring system as grade 2 (mild) and grades 3, 4, or 5 (serious). One of 75 patients treated with IC RT only experienced a grade-2 complication (proctitis). Of 71 patients receiving 4-field EX RT only, 25 preop (16%) and 14 postop (14%) patients had complications. Of 139 patients treated with both EX and IC RT, grade-2 complications were seen in 5% of 87 preop patients and 12% of 52 postop patients (p = 0.17), whereas serious complications were observed in 4% of each group. Univariate analysis of the variables of interest revealed that the incidence of complications was associated with a lymphadenectomy (p = .03), use of external RT (p less than .01), and decreasing age (p = .04). Multivariate analysis confirmed that use of external RT was the most significant predictor for complications. In conclusion, similar complication rates were found in patients treated with either preop or postop 4-field EX RT. While pelvic RT clearly decreases pelvic relapse in patient with endometrial carcinoma, the risk benefit ratio for treatment of these patients should be carefully considered when recommending adjuvant RT for pelvic control. PMID- 1917621 TI - The effect of overall treatment time on the outcome of definitive radiotherapy for localized prostate carcinoma: the Radiation Therapy Oncology Group 75-06 and 77-06 experience. AB - From 1976 to 1983, 1091 patients were entered into RTOG protocols 75-06 and 77 06. Of these, 780 patients complied with protocol requirements, received a minimum tumor dose of greater than or equal to 6500 cGy, and received no endocrine therapy. There were 78, 342, and 360 patients with localized prostate carcinoma, Stages T1b(A2), T2(B), and T3,4(C), respectively. The potential follow up period ranges from 6 years 5 months to 13 years 3 months, with a median follow up of 9 years. This study examines the influence of overall treatment time on the outcome of definitive radiotherapy for localized prostate carcinoma in this patient population. Within each stage, patients were divided into three groups according to the total number of elapsed days while on treatment: within 49 days (less than or equal to 7 weeks); 50 to 63 days (8 to 9 weeks); and greater than or equal to 64 days (greater than 9 weeks). Based on actuarial analysis, within each stage, the overall treatment time did not have any impact on the following: overall survival, NED survival, or local/regional control. When grouped under different histologic grades, that is, Gleason scores 2-5, 6-7, and 8-10, the actuarial local/regional control showed no statistical difference among the three groups. The actual local/regional failures were analyzed and stratified by stage and Gleason scores, and no statistical difference was noted among the three groups for each stratification. The range of local/regional failure rates among the three groups for T1b(A2), T2(B), and T3,4(C) disease were 0%-8%, 16%-23%, and 24%-27%, respectively. The corresponding range of local/regional failure rates for patients with Gleason scores of 2-5, 6-7, and 8-10 were 13%-14%, 18%-22%, and 22%-33%, respectively. The incidence of late complications was not related to the number of elapsed treatment days. Therefore, the overall treatment time does not have an impact on the outcome of definitive radiotherapy for localized prostate carcinoma. It is hypothesized that prostate carcinoma behaves as late-reacting tissue in which there is little, if any, accelerated repopulation of clonogenic tumor cells during the later half of a protracted course of radiotherapy. This observation is in direct contrast to that suggested for head and neck carcinoma and bears important implications in daily radiotherapeutic management of patients with prostate carcinoma. PMID- 1917622 TI - Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706. AB - Significant late intestinal and urinary morbidity from external beam irradiation for adenocarcinoma of the prostate has been a constant concern of both the urologist and the radiation oncologist. We analyzed two large Radiation Therapy Oncology Group trials (7506 and 7706) using primary irradiation in the treatment of local or locoregional adenocarcinoma of the prostate to assess morbidity via the Radiation Therapy Oncology Group scoring scheme (grade 1-5). One thousand twenty patients were treated in total with a minimum follow-up of 7 years in the surviving patients. There was a 3.3% incidence of intestinal complications defined as grade 3 toxicity or more with .6% of patients experiencing bowel obstruction or perforation. Urinary complications defined as grade 3 toxicity or more were found in 7.7% of patients with only 0.5% experiencing morbidity that would require a major surgical intervention such as laparotomy, cystectomy, or prolonged hospitalization. Intestinal and urinary complications were evaluated in reference to several parameters that might have an impact on their incidence (i.e., previous laparotomy, stage of disease, hypertension, positive lymph nodes, previous transurethral resection, total dose, and energy of accelerator used). Only total dose (greater than 70 Gray) was found to have a significant impact on the incidence of the urinary complications. None of these factors had a significant impact on the incidence of intestinal complications. These data from two large multi-institutional trials represent a fair estimate of the actual incidence of major intestinal and urinary complications from external beam irradiation in the management of local and locoregional adenocarcinoma of the prostate. Since the incidence of these major complications remains very low, we believe that external beam irradiation remains an excellent alternative to radical prostatectomy in the management of these patients. PMID- 1917623 TI - Multivariate analysis of factors predicting local relapse after radical prostatectomy--possible indications for postoperative radiotherapy. AB - Between 1970 and 1983, 273 patients underwent radical surgery (radical prostatectomy--261, radical cystoprostatectomy--12) for newly diagnosed adenocarcinoma of the prostate at Duke University Medical Center and received no adjuvant radiotherapy. A total of 46 patients developed local recurrence. Forty developed local relapse only and six developed simultaneous local and distant failure. The crude local relapse rate was 17% (46/273). The actuarial local failure rate at 5, 10, and 15 years was 12%, 32%, and 35%, respectively. Univariate and multivariate analyses were performed to identify factors predictive of local relapse after radical surgery. Possible prognostic factors analyzed were: age, type of biopsy, use of adjuvant hormonal therapy, histologic grade, histologic involvement of seminal vesicles, positive surgical margins, clinical stage, and elevated acid phosphatase. Factors identified as significant predictors of local relapse by univariate analysis were: poorly differentiated histology (p = 0.0001), seminal vesicle involvement (p = 0.0009), and positive surgical margins (p = 0.0001). An elevated preoperative acid phosphatase was of borderline significance (p = 0.06). On multivariate analysis, poorly differentiated histology (p = 0.0007), positive margins (p = 0.0015), and elevated acid phosphatase (p = 0.0273) were significant predictors of local failure. Seminal vesicle involvement was no longer a significant predictor of local failure. However, on subsequent univariate and multivariate analyses, seminal vesicle involvement was the only significant predictor for the development of distant metastases (p = 0.0019, multivariate). Thus, patients with poorly differentiated tumors, positive surgical margins, or elevated preoperative acid phosphatase are at high risk for local relapse after radical prostatectomy. These patients should be included in future clinical trials studying the role of adjuvant radiotherapy after radical prostatectomy, or offered adjuvant radiotherapy if they cannot or will not participate in such trials. PMID- 1917624 TI - Radiotherapy following radical prostatectomy in patients with adenocarcinoma of the prostate. AB - From 1973 to 1986, 160 patients with adenocarcinoma localized to the prostate were treated with radical prostatectomy and pelvic lymphadenectomy. In 78 (49%) patients more advanced stage of disease was found at surgery and they received local pelvic irradiation (RT). This consisted of 45 Gy for microscopic and 55 Gy for macroscopic residual disease. RT was given at 1.8 Gy a day, using the four field "box" technique with the 23 MV X ray beam. Pelvic lymph node metastases were found in 28 (36%) patients who, in addition to RT, received systemic therapy: 20 with cyclophosphamide alone, 4 combined with 5-Fluorouracil, and 4 patients received DES. The 5- and 10-year overall actuarial survival was 95 and 77%, respectively, and the 5- and 10-year disease-free survival was 58 and 43%, respectively. Recurrent tumor was found in 34 (44%) patients. Of these 34 patients, 32 (94%) had distant metastatic tumor and 2 (6%) had local recurrence in the pelvis. The presence of metastatic disease in pelvic lymph nodes had clinical significance since it influenced disease-free survival and the incidence of tumor recurrence. The 10-year disease-free survival for the 50 patients with no lymph node metastases was 51%, as compared to 28% for the 28 patients with such metastases, p = 0.001. Similarly, recurrent tumor was found in 28% of the former and 68% of the latter patients, p = 0.002. Other important parameters predicting recurrence were: clinical stage, p = 0.018, histological grade, p = 0.013, and Gleason's grade, p = 0.002. This treatment program was very well tolerated and of low toxicity. There was no surgical mortality. Surgical complications were seen in 10 (13%) patients including: minor in 5 and major in 5. At 1 year, 77% of the patients remained continent, while 10% had mild stress incontinence. Of the remaining 13% only 3 (4%) patients had severe incontinence (greater than 5 pads daily). RT toxicity was mild with 38% experiencing diarrhea. Severe toxicity was seen in 2 (3%) patients who, early in the study, developed scrotal and lower extremity edema. Severe chemotherapy complications were seen in 1 (4%) patient who had severe neutropenic sepsis. Postoperative radiotherapy is a well tolerated, safe and effective treatment in patients who have microscopic or macroscopic residual tumor following radical prostatectomy. PMID- 1917625 TI - External beam irradiation versus 125 iodine implant in the definitive treatment of prostate carcinoma. AB - We reviewed the record of all 983 patients seen at the Hahnemann University, Department of Radiation Oncology for evaluation of prostate cancer during the megavoltage era. We compared the results of 276 patients who were treated definitively with either external beam irradiation or Iodine 125 implantation. The groups were similar in most prognostic characteristics. Where appropriate, multivariate statistical techniques were used to compensate for the effects of differences in grade and stage between the two groups. There were striking differences between implant and external beam patients in both local failure rates and disease-free survival, mostly attributable to poor local control in the implant patients. Thirty-eight percent of the Stage A and B implant patients failed locally in the first 5 years whereas only 5% of a comparable group of external beam patients did so. A2 patients, however, exhibited similar disease free survival in both cohorts. Complication rates were 11% in the implant group and 19% in the external beam group. We conclude that there are serious doubts about the efficacy of Iodine 125 implantation in maintaining local control, and that this translates into worse relapse-free survival. By contrast, local control and relapse-free survival may be satisfactory in the A2 patients, and complication rates may be lower with implant. The above suggests that Iodine 125 interstitial implantation is well suited to only a minority of early stage prostate cancer patients and that most patients with Stage B and C prostatic carcinoma should be treated with either external beam irradiation or with radical prostatectomy. PMID- 1917626 TI - A comparison of the roles of surgery and radiation therapy in the management of carcinoma of the female urethra. AB - Between 1939 and 1986, 42 patients with carcinoma of the female urethra were treated with surgery and/or radiation therapy at the University of Iowa. Ten patients were treated with surgery alone, 28 with radiation therapy alone, and 4 with combined surgery and radiation therapy. Seventeen patients (40%) developed persistent or recurrent disease at the primary site and 15 (36%) had failures in the inguinal nodes. The actuarial 5-year survival rate was 33.5%. Only 36% (10/28) of patients treated with radiation therapy had local failures, compared to 60% (6/10) of those treated with surgery alone. The best results were achieved with combined interstitial and external beam irradiation. Whereas 57% (8/14) of patients who were treated with combined interstitial and external beam irradiation were alive NED at 3 years, none of 7 patients (0%) treated with interstitial implants only and 2 of 7 patients (29%) treated with external beam irradiation alone were alive NED at 3 years. There was a significantly lower inguinal failure rate in patients who received treatment to the inguinal nodes (10%) than in those who did not receive inguinal area treatment (52%), and this translated into a superior 5-year survival for those patients (60% vs 18%). Survival rates did not correlate with histopathologic type in this series, although there were differences in the patterns of failure. Survival rates did correlate well with clinical stage. PMID- 1917627 TI - Effect of oxygen level on the enhancement of tumor response to radiation by perfluorochemical emulsions or a bovine hemoglobin preparation. AB - Attempts to correct tumor hypoxia with oxygen-carrying solutions have used high concentrations of inspired oxygen (FiO2 100% or 95%). In the clinic, however, obtaining such high levels of FiO2 using mask ventilation in older patients or in children may be difficult. Since lower levels of FiO2 had not been previously tested, we examined the antitumor efficacy of FiO2 levels of 65, 85, and 95% breathed for 1 hr prior to and during irradiation used with the concentrated perfluorochemical emulsion F44E, the less concentrated emulsion, Fluosol-DA, or a new preparation consisting of purified bovine hemoglobin solution, PBHS. When tested in mice bearing the Lewis lung carcinoma with 2, 3, or 4 Gy daily for 5 days, daily Fluosol-DA produced only a small increase in the slope of the tumor growth delay versus irradiation alone, when used with 85% FiO2 (dose modifying factor [DMF] 1.3), but produced a DMF of 2.1 with 95% FiO2. Various concentrations of F44E (2, 4, or 8 g PFC/kg) each required a 95% FiO2 for full effect but the 8 g/kg dose had a discernable effect with an FiO2 of 65% and 85% (DMF 1.25 and 1.30, respectively). For PBHS, in contrast, a DMF of 1.6 was observed at 20% FiO2, but surprisingly this increased further to 2.1 with 95% FiO2. Further investigations of PBHS with irradiation demonstrated that daily administration of PBHS (12 ml/kg) 1 hr before single Xray fractions of 5, 10, 15, or 20 Gy with 20% FiO2 resulted in a DMF of 1.6-1.7 in the FSaIIC fibrosarcoma compared with irradiation alone when ascertained by tumor cell excision assay. These results indicate that to achieve maximum antitumor benefit with these oxygen-carrying solutions with radiation therapy, care must be taken to insure that FiO2 levels near 100% are achieved. PMID- 1917628 TI - Low dose rate irradiation and halogenated pyrimidine effects on human cervical carcinoma cells. AB - The response of two human cervical carcinoma cell lines to the combination of bromodeoxyuridine (BrdUrd) incorporation and low dose rate irradiation (LDRI) was assessed. Survival curves were generated following both acute (67.2 Gy/hr) and low dose rate (0.11-0.62 Gy/hr) 137Cs gamma-ray irradiation. The two cell lines exhibited markedly different radiation responses, but for the chronic irradiation, there was no significant difference in response between the low dose rates for either cell line. In all cases, the low dose rate radiation response could be described using a single exponential y = e-alpha D. The sensitizer enhancement ratio (SER) at 10% survival was determined and for the first cell line the low dose rate slope (alpha) was approximately 0.7 Gy-1 with an SER of 1.3-1.5 and an SER of approximately 1.6 for the acute response. In contrast, the second cell line had a low dose rate slope (alpha) of approximately 0.4 Gy-1, an SER of 1.3-1.5, and an SER of approximately 1.7 for the acute response. The similarity of the SER's is notable in light of the marked differences between the intrinsic radiation response of the cells. As the concentration and/or time of exposure to BrdUrd increased, both cytotoxicity and the degree of sensitization also increased. This study demonstrates that SER's with BrdUrd and LDRI are comparable to those obtained for acute exposures in two cervical carcinoma cell lines. The results suggest that this combination of modalities may have clinical applications. PMID- 1917629 TI - Quantitative histological changes in a human melanoma xenograft following exposure to single dose irradiation and hyperthermia. AB - The purpose of the present paper is, in terms of quantitative histology, to explain the growth response of a human melanoma xenograft after exposure to single dose irradiation (7.5 Gy, 15.0 Gy, and 25.0 Gy) and hyperthermia (42.5 degrees C for 60 min). Data from several experiments on the mitotic activity, the occurrence of different modes of cell death and reproductively dead cells in the tumors are discussed. The tumor cell proliferation is only transiently reduced after 7.5 Gy and 15.0 Gy, and tumor regression mainly results from an increased cell loss. Cell loss through apoptosis and cell disintegration during mitosis show a dose-dependent increase after irradiation. Although the fraction of necrosis, relative to the number of tumor cells, increases after 7.5 Gy and 15.0 Gy, the cell loss through necrosis, that is, the production of necrosis, is probably reduced. Compared to the cell loss through apoptosis and mitotic death, the removal of necrosis is probably less important in determining the regression rate of the tumors after 7.5 Gy and 15.0 Gy. After 25.0 Gy the cell production is markedly reduced, and cell loss increases, partly due to radiation injury to the vascular system, resulting in necrotization of the tumor core. Thereafter, the tumor regression rate depends mainly on the rate of necrosis removal. The mitotic activity of remaining cells is not reduced after hyperthermic treatment, and the tumor growth response is a result of an increased cell loss. Although the occurrence of apoptosis and cell disintegration in mitosis increases after hyperthermia, these modes of cell loss are of minor importance for the tumor regression after treatment. The increased cell loss is mainly due to massive necrosis formation in the central tumor areas, a result of heat injury to tumor blood vessels. After necrotization of the tumor core, the regression rate depends mainly on the rate of necrosis removal. PMID- 1917630 TI - A dosimetric analysis of Morris, Fletcher, and Henschke systems for treatment of uterine cervix carcinoma. AB - The role of intracavitary irradiation in the treatment of uterine cervix carcinoma is well established, and over the years a number of different systems for intracavitary irradiation have been developed. To compare the clinical efficacy of different systems and to develop guidelines for the design of applicators with new sources such as americium-241, we present a dosimetric comparison of three systems: (a) the Morris system, a modified Stockholm technique; (b) the Henschke system; and (c) the Fletcher system. Using a computerized planning system, dose distributions with different configurations of each system were calculated. For each case, doses to point A, B, and a set of reference points representing bladder and rectum were also calculated. Also, the 60 Gy reference volumes, as defined by ICRU Report No. 38, 1985, were calculated for six different treatment regimens. These treatment regimens employ widely different combinations of whole pelvis external beam dose, split pelvis external beam dose, and intracavitary irradiation dose to achieve similar clinical outcomes for the treatment of various stages of cervix carcinoma. From this analysis we observe the following: (a) The Morris system produces a higher dose rate to point A (70 to 90 cGy/hr) compared to the Fletcher or Henschke system (50 to 70 cGy/hr); (b) the doses to point B relative to point A dose are about the same for all three systems at 28 to 32%; (c) the doses to reference rectum and bladder points relative to point A dose for clinically equivalent configurations are about the same for Fletcher and Henschke systems (58-65%) not including the effects of shields in the vaginal ovoids, and somewhat higher for the Morris system (72-79%); (d) the volume treated to a given dose rate by each intracavitary system alone is about the same; and (e) the 60 Gy volume depends critically upon the external beam whole pelvis dose, rising steeply as the external beam whole pelvis dose approaches 30 Gy. Since different groups have used widely different prescriptions of external beam whole pelvis dose, ranging from 0 to 50 Gy depending upon stage, the 60 Gy volumes for these various dose prescriptions are strikingly different. Because the Morris system uses lower values for the external beam whole pelvis dose than the others, its 60 Gy volume for the advanced Stage IIB and IIIB is 2 to 4 times lower than others. This choice makes the Morris system more conservative than others, probably resulting in slightly lower cure rates for the advanced stage disease. PMID- 1917631 TI - Protection of pets in Israel against chemical warfare agents. PMID- 1917632 TI - Comments on aldicarb toxicosis in cattle. PMID- 1917633 TI - Treatment of bacterial endocarditis in cattle. PMID- 1917634 TI - Colonel Alm recounts vital role of veterinarians in Persian Gulf conflict. PMID- 1917635 TI - Service to the country and the profession. PMID- 1917636 TI - New Internal Revenue Service ruling may affect many personal service corporations. PMID- 1917637 TI - Manufacturer's liability for defective veterinary products. PMID- 1917638 TI - Cache Valley virus infection in Texas sheep flocks. AB - Cache Valley virus (CVV), an arbovirus indigenous to the United States, has been implicated as an important teratogenic agent in sheep. The prevalence and distribution of Texas sheep with CVV-specific antibody were investigated. In 1981, 19.1% of 366 sheep located in 22 counties of Texas had antibodies specific for CVV. Of 50 flocks examined in the major sheep-producing counties in Texas, 34 had sheep with antibodies that reacted with CVV, including all sheep tested in 6 flocks that were seropositive. Sera obtained from sheep at the Texas Agricultural Experiment Station at San Angelo between 1986 and 1989 were also examined for CVV specific antibody because this flock was the subject of the episode of CVV associated congenital malformations during the 1986 and 1987 lambing season. Approximately 8.6% of 104 sheep in 1986, 63.4% of 164 in 1987, 11.3% of 44 in 1988, and 71.9% of 89 in 1989 from the Texas Agricultural Experiment Station at San Angelo tested were seropositive. The data indicate that CVV infections in sheep were widespread in Texas in 1981 and that the virus is enzootic in sheep at the Texas Agricultural Experiment Station in San Angelo, where the episode of congenital malformations had initially been reported in 1987. PMID- 1917639 TI - Antibiotic and sulfonamide residues from Food Safety Inspection Service bob veal calf tissues by region, from October 1987 to September 1988. AB - Of 3,095 bob veal carcasses declared positive to the calf antibiotic and sulfonamide test (CAST) performed by USDA-FSIS personnel during the fiscal year 1988, 967 were submitted to USDA-FSIS laboratories for intensified antimicrobial evaluation of kidney, liver, and muscle specimens. In the western region, CAST positive specimens were analyzed from certified calves, that is, calves declared free of antimicrobials by their producers. In the midwestern and eastern regions, 20% of the CAST-positive carcass submissions were certified and 20% had not been certified. Among the regions, neomycin was the most commonly reported agent from kidney specimens; however, there were some distinct differences among regions (24.6% of the specimens in the Midwest, 37.4% in the East, and 46.8% in the West). Reports of gentamicin in specimens also were different among regional laboratories (9.0% in the Midwest, 12.1% in the East, 3.1% in the West). Sulfamethazine was less frequently reported by the western laboratory, never exceeding 2% among the 3 tissues tested, whereas the eastern and midwestern laboratories had at least 1 tissue type that was greater than or equal to 9%. Not all specimens were subjected to sulfonamide evaluation. Regional patterns were noticed for unidentified microbial inhibitors, which were most evident for liver in which 24.6% of the specimens at the western laboratory were classified as having unidentified microbial inhibitors, and only 6.3% of specimens at the eastern laboratory were classified as having unidentified microbial inhibitors. PMID- 1917640 TI - Effects of castration on chronic bacterial prostatitis in dogs. AB - An Escherichia coli bacterial prostatitis was experimentally induced in dogs to determine the effect of castration on chronic bacterial prostatitis. Two weeks after instillation of bacteria directly into the prostate gland, 17 of 22 adult mixed-breed male dogs had positive urine or prostatic fluid cultures or both. Seven of the 17 dogs were randomly chosen to be castrated, and 10 of the 17 served as sham-operated controls. At weekly intervals, urine was obtained from 17 dogs for aerobic microbiologic culturing. At each week, dogs with no bacterial growth in the cultured urine had prostatic fluid collected for aerobic microbiologic culture. Dogs with negative urine, prostatic fluid, and prostatic tissue needle biopsy culture results at week 7 were euthanatized. For remaining dogs, weekly cultures were continued until the dogs were euthanatized at week 12. None of the 7 castrated dogs and 6 of the 10 dogs subject to sham operation had prostatic infection at the time of necropsy. The castrated dogs had a mean infection duration of 4.2 weeks, which was statistically shorter than the 9.5 week mean duration of infection in the sham-operated controls. Cultures of prostatic tissue obtained immediately after euthanasia correlated 100% with urine and prostatic fluid cultures taken before euthanasia. All of the 6 dogs with positive prostatic cultures at termination had moderate to marked lymphoplasmacytic chronic prostatitis. The 11 dogs that were not infected at the end of the study had normal to moderate lymphoplasmacytic chronic prostatitis on histologic examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917641 TI - Leptospira interrogans serovar bratislava infection in two dogs. AB - Two dogs with clinical histories suggestive of leptospirosis were examined serologically and culturally for evidence of leptospiral infection. Antibodies to Leptospira interrogans serovar bratislava were detected in serum from one dog, and the organism was isolated from urine of that dog. In a serologic survey of dogs in the state of Illinois, reactor rates to bratislava were higher than those to canicola or icterohaemorrhagiae. In cases of suspect canine leptospirosis, serovars such as bratislava, not contained in canine vaccines, should be considered in a differential diagnosis. PMID- 1917642 TI - Hyponatremia and hyperkalemia associated with idiopathic or experimentally induced chylothorax in four dogs. AB - Two dogs with idiopathic chylothorax and 2 dogs with experimentally induced (ie, ligation of the cranial vena cava) chylothorax were treated by intermittent thoracic drainage. Of these 4 dogs, 3 that did not have evidence of renal failure had normal or near-normal serum sodium and potassium concentrations before thoracic drainage began, and all 3 developed repeatedly marked hyponatremia and hyperkalemia during thoracic drainage. Another dog became weak and depressed, ostensibly because of hyperkalemia. Serum sodium and potassium concentrations in 1 dog with spontaneous chylothorax returned to normal after chylothorax resolved and thoracic drainage was stopped. The other 3 dogs died or were euthanatized, and the effect of stopping thoracic drainage could not be evaluated. In 3 dogs in which it was measured, normal-to-high plasma cortisol concentration was observed before and after adrenocorticotropin administration, and 2 dogs also had hyperaldosteronemia. Hyponatremia was hypothesized to be caused by sodium loss via thoracic drainage whereas hyperkalemia may have been multifactorial in origin, but probably was attributable, at least, in part to decreased renal potassium clearance. PMID- 1917644 TI - Staphylococcus hyicus abortion in a sow. AB - Five aborted fetuses from a mature sixth-parity sow with severe greasy pig disease as a gilt, were submitted for diagnostic evaluation. Necropsy of the fetuses revealed serogelatinous edema in the SC connective tissue of the ventral abdominal region (especially around the umbilicus), exaggerated amounts of serohemorrhagic fluid in the abdominal, pleural, and pericardial cavities, and hemorrhagic kidneys, with diminished consistency. Staphylococcus hyicus was isolated in pure culture from liver, lung, kidney, and brain tissues and from abdominal, pleural, pericardial, and gastric fluids. PMID- 1917643 TI - Cytosine arabinoside chemotherapy for acute megakaryocytic leukemia in a cat. AB - Myeloproliferative disease in a cat was characterized by severe, nonregenerative anemia, circulating blast cells, and proliferation of bizarre megakaryoblasts in the bone marrow. The number of circulating platelets was markedly higher than normal at initial examination. Chemotherapy with cytosine arabinoside was successful in inducing complete remission and maintaining survival for 122 days. PMID- 1917645 TI - Repair of an open radial fracture in an adult horse. AB - An open radial fracture in an adult horse (450 kg) was repaired by internal fixation, using two 18-hole 4.5-mm broad dynamic compression plates and 5.5- and 4.5-mm bone screws. The fracture healed completely, but when evaluated 9 months after surgery, the horse was lame on the fractured limb at a trot. Local infiltration of anesthesia along the distal half of the bone plates greatly ameliorated the lameness, suggesting that the plates were irritating the soft tissues and extensor tendons along the cranial and lateral aspects of the antebrachium. Both bone plates were removed simultaneously with no complications, and the horse became sound. PMID- 1917646 TI - Nonsurgical removal of chondroid masses from the guttural pouches of two horses. AB - Chondroid masses were successfully removed from the guttural pouches of 2 horses, using an endoscope, a snare, and a vacuum pump. This technique is an alternative to surgical removal of chondroid masses in patients when basic lavage of the affected guttural pouch is ineffective. Complications were not encountered. Advantages of this snare technique include avoidance of surgery and its potential complications, minimal recovery time, and minimal expense. PMID- 1917648 TI - Types of colic and frequency of postcolic abortion in pregnant mares: 105 cases (1984-1988). AB - The records of 105 pregnant mares and 105 nonpregnant horses with colic admitted to an equine hospital were reviewed. The 2 groups had similar types of colic and short-term survivability. Of the 105 pregnant mares, 31 were treated medically and 74 required surgical intervention. Thirty-three of the 105 mares died or were euthanatized. Thirteen (18%) of the 72 remaining mares aborted. Of 4 mares with severe medical cases, 2 died, 1 aborted, and 1 aborted and died. Of 27 horses with medical cases that required less intensive treatment, none died and 2 aborted. Of the 74 horses that required surgery, 45 survived to termination of pregnancy (foaling or abortion); 36 of these mares (80%) had a live foal. The type of surgical lesion had no effect on pregnancy outcome. Stage of gestation at initial examination, duration of anesthesia, or intraoperative hypoxia or hypotension had no effect on pregnancy outcome. However, when hypoxia occurred during colic surgery in the last 60 days of pregnancy, the mares either aborted or delivered severely compromised foals that did not survive. PMID- 1917647 TI - Ultrasonographic evaluation of horses with thrombophlebitis of the jugular vein: 46 cases (1985-1988). AB - Medical records of 46 horses with jugular vein thrombophlebitis that were evaluated ultrasonographically were reviewed. The ultrasonographic appearance of the thrombus within the jugular vein was classified as noncavitating if it had uniform low to medium amplitude echoes, or as cavitating if it was heterogenous with anechoic to hypoechoic areas representing fluid or necrotic areas within the thrombus, and/or hyperechoic areas representing gas. Signs of pain on palpation of the affected vein (P less than 0.001), heat over the vein (P = 0.001), and swelling of the vein (P less than 0.05) were significantly associated with the ultrasonographic detection of a cavitating lesion. Ultrasonography also was useful for selecting a site for aspiration of a specimen for bacteriologic culturing and susceptibility testing. PMID- 1917649 TI - Diseases of mynahs. PMID- 1917650 TI - What is your diagnosis? Soft tissue mass in the left retroperitoneal space. PMID- 1917651 TI - FAVOR urges proactive stance on extra-label use. PMID- 1917652 TI - A pathfinder. PMID- 1917653 TI - Why we don't (or won't) delegate. PMID- 1917654 TI - Integrating veterinary services into disaster management plans. PMID- 1917655 TI - Movers and shakers. PMID- 1917656 TI - Partial budget analysis of vaccinating dairy cattle against coliform mastitis with an Escherichia coli J5 vaccine. AB - Partial budget analysis of clinical coliform mastitis prevention supported vaccination of dairy cows with an Escherichia coli J5 vaccine. Increased profits of $57/cow lactation were predicted using a computer spreadsheet derived partial budget with generalized herd input data. Herd vaccination programs were predicted to be profitable when greater than 1% of cow lactations resulted in clinical coliform mastitis. Herd vaccination programs were predicted to be profitable at all herd milk production levels. PMID- 1917657 TI - Evaluation of the safety of ivermectin administered in a beef-based formulation to ivermectin-sensitive Collies. AB - Twenty-four Collies sensitive to the toxic effects of ivermectin, when administered at high dosages, were studied to evaluate the effects of repeated monthly treatment with an ivermectin beef-based formulation at amounts up to 10 times the dosage recommended for heartworm prevention in dogs. Collies were treated 3 times at 30-day intervals at rates of 12, 36, or 60 micrograms of ivermectin/kg of body weight, or with vehicle. Complete physical and neurologic examinations were performed on all dogs prior to the first treatment and after the final treatment. Clinical observations and ivermectin reaction scores were recorded daily for each dog throughout the study. Clinical or neurologic signs characteristic of ivermectin toxicosis were not observed for any dog during the study. Single episodes of vomiting were recorded for 2 vehicle-treated dogs and 2 dogs treated with ivermectin at 12 micrograms/kg from 6 to 21 days after treatment. At the end of the study, all dogs were challenge-exposed with ivermectin at 120 micrograms/kg to reconfirm their sensitivity to this class of compounds. All dogs developed signs typical of ivermectin toxicosis during the subsequent 48- to 72-hour period. Results of this study demonstrated that ivermectin can be administered repeatedly without adverse effects at rates up to 60 micrograms/kg (10 times the recommended use level) to Collies known to be sensitive to this drug. PMID- 1917658 TI - Staggers induced by consumption of perennial ryegrass in cattle and sheep from northern California. AB - Staggers was diagnosed in sheep and cattle from the northern California coast. The diagnosis was made on the basis of history of ingestion of perennial ryegrass (Lolium perenne) stubble, clinical signs of transient ataxia, which was aggravated by stimulation, and nearly complete recovery after removal of ryegrass as the primary forage. Morbidity was high, but death did not occur in any affected animals. The toxic endophyte, Acremonium lolii, was in most lower leaf sheaths from the ryegrass. Injection of extracts of the ryegrass from affected farms into mice induced signs of toxicosis. Additionally, ryegrass from all 3 farms contained the tremorgenic mycotoxin, lolitrem-B. PMID- 1917659 TI - Botulism associated with feeding alfalfa hay to horses. AB - Botulism was believed to be the cause of progressive symmetric myasthenia in 8 horses on a farm in North Carolina. One horse was found dead, 6 were euthanatized after becoming recumbent, and 1 affected horse recovered. Cecal and colonic contents of 2 horses were determined to contain Clostridium botulinum spores. Alfalfa hay that was fed to the horses contained spores and toxin. PMID- 1917660 TI - Toxoplasmosis in two cats with inflammatory intestinal disease. AB - Lymphocytic-plasmacytic enteritis, a chronic inflammatory intestinal disease, was diagnosed in 2 cats. In 1 cat, recurrence of clinical signs after initiating treatment was attributed to relapse of the inflammatory intestinal disease, but was found to be attributable to relapsing toxoplasmosis secondary to immunosuppressive drug therapy. Treatment with clindamycin resolved the recurrent toxoplasmosis. In the second cat, clinical signs of toxoplasmosis did not develop, but serologic testing yielded evidence of active toxoplasmosis. Treatment with clindamycin caused the titers to decrease. Relapsing toxoplasmosis may be responsible for apparent resistance to treatment in cats for inflammatory intestinal disease being treated with immunosuppressive drugs. PMID- 1917661 TI - Tracheal obstruction caused by tree needles in a cat. AB - Tracheal obstruction was suspected in a 1-year-old female domestic shorthair cat. Clinical signs consisted of inspiratory and expiratory dyspnea and cyanosis. The cat did not improve when treated with oxygen, epinephrine, prednisolone sodium succinate, and aminophylline. Bronchoscopy revealed obstruction of the trachea and carina by a 2.5-cm twig and needles from a Douglas fir tree. Needles had migrated into distal airways. The cat was euthanatized at the owner's request. PMID- 1917662 TI - Surgical treatment of a congenital bronchoesophageal fistula in a dog. AB - A 1-year-old male Cairn Terrier was evaluated for chronic coughing that was aggravated by eating or drinking. Radiography revealed an esophageal diverticulum, regional megaesophagus, and focal interstitial densities in the right caudal and middle lung lobes. Using fluoroscopy and contrast radiography, contrast material was seen to accumulate in the diverticulum and to reflux into the right middle, caudal, and accessory bronchi. Radiographic diagnosis was bronchoesophageal fistula. Via right eighth intercostal space thoracotomy, the abnormal connection between esophagus and caudal lobe of the right lung was identified, the lobe was resected, and the esophagus was closed. Histologic examination of the connecting tissue revealed a lining of stratified epithelium, with the superficial layer being predominantly ciliated columnar epithelium. Several findings led to the conclusion that the fistula was a congenital lesion, arising from aberrant formation of the respiratory tract from the embryologic digestive tract. Histologic examination revealed smooth muscle and lack of inflammation in tissue surrounding the fistula, which are criteria for identifying congenital bronchoesophageal fistula in human patients. The dog was young and did not have a history of esophageal foreign bodies. Postoperative complications were not encountered, and 9 months later, the dog was reported to be eating dry dog food without coughing. Congenital and acquired bronchoesophageal fistulas in dogs are reported infrequently. Furthermore, 2 of 12 previously reported bronchoesophageal fistulas in dogs, one of which was considered congenital, developed in Cairn Terriers. PMID- 1917663 TI - Probable congenital esophageal stenosis in a thoroughbred foal. AB - Esophageal stenosis was diagnosed in a 7-day-old Thoroughbred foal referred for evaluation of bilateral milky nasal discharge. Double-contrast radiography revealed concentric narrowing of the esophagus at the level of the fifth rib, overlying the base of the heart. Lateral displacement of the esophagus was not apparent. X-ray computed tomography of the cranial portion of the thorax confirmed normal cardiac and great vessel anatomy, ruling out vascular ring anomaly. A nasogastric tube was placed, extending past the stenosis and into the stomach, and the foal was fed mares' milk via this tube. On day 14, the foal was allowed to nurse the mare hourly and was made to stand, with the cranial half of its body elevated for 5 minutes after each feeding. On day 19, the foal was allowed to nurse ad libitum and eat hay and grain with the mare. Signs of regurgitation and aspiration were not apparent. On day 29, the foal was discharged to the owner. PMID- 1917664 TI - Mesothelioma in cattle: eight cases (1970-1988) AB - Over an 8-year period, 8 beef cattle with mesothelioma were admitted to the Auburn University College of Veterinary Medicine and the Louisiana State School of Veterinary Medicine. Diagnosis was confirmed by histologic examination of affected tissues. Five bulls, 1 steer, and 2 cows were affected. Four of the bulls had scrotal swelling; 2 cows and 1 bull had ventral abdominal swelling. The peritoneal cavity was involved in 5 cases, the pleural cavity was affected in 2 cases, and in 2 cases, disease was apparently confined to the vaginal cavity. Of the 8 cattle, 6 died or were euthanatized; only cattle with tumor apparently confined to the vaginal cavity survived. PMID- 1917666 TI - Fringe benefits received by veterinarians, 1989. PMID- 1917665 TI - Ultrasonographic findings in dogs and cats with oxalate nephrosis attributed to ethylene glycol intoxication: 15 cases (1984-1988). AB - Renal ultrasonographic findings in 12 dogs and 3 cats determined to have oxalate nephrosis presumed to be secondary to ethylene glycol intoxication were examined. Ultrasonographic changes varied from mild to marked increases in renal cortical echogenicity. A pattern of greater than normal cortical and medullary echogenicity with persistence of areas of lesser echo intensity at the corticomedullary junction and central medullary regions was observed. This pattern, termed the halo sign, was recognized in 7 dogs and 1 cat concurrent with the development of clinical anuria. Ultrasonographic patterns in these clinical cases were similar to those observed in a previous study of dogs with experimentally induced ethylene glycol nephrosis. Ultrasonographic findings were not considered pathognomonic of ethylene glycol nephrosis. Due to the high death rate reported in the cases surveyed, detection of ultrasonographic changes was considered to warrant a guarded to poor prognosis. Because of the association of the halo sign with anuria, its detection was considered to warrant a grave prognosis. PMID- 1917667 TI - What is your diagnosis? Radiologic diagnosis--patent ductus arteriosus. PMID- 1917668 TI - Ratios of cross-sectional areas of muscles and their tendons in a healthy human forearm. AB - The muscles and tendons in the forearm and hand of a young man, amputated after an accident, have been weighed and measured. The physiological cross-sectional areas of those muscles that had long tendons were 35 +/- 9 (mean and standard deviation) times the cross-sectional areas of the tendons. The mean is very close to the optimum calculated from the theory of Ker, Alexander & Bennett (1988). It implies that the tendons experience stresses of about 11 MPa and strains of about 1.3%, when the muscles exert their maximum isometric forces. Very much larger forces would be needed to break the tendons. PMID- 1917670 TI - Effects of excess iodine in chick embryo thyroid follicles: initial inhibition and subsequent hypertrophy. AB - The effects of excess iodine on the development of the thyroid gland of chick embryos was assessed following injections of potassium iodide prior to incubation. Iodide injection resulted in a significantly greater thyroid gland weight (goitre) on Day 18 of incubation and a delay in hatching. Histological studies of the thyroid gland on Day 12 of incubation revealed that iodide injection had inhibited thyroid follicle development. On Day 14, however, the thyroid glands of the iodide-treated embryos were indistinguishable from controls and on Day 18 the thyroid follicles of the iodide-injected embryos were clearly hypertrophied. In agreement with these light microscopical observations, electron microscopical examination showed conspicuous development of rough endoplasmic reticulum in the follicle cells of both iodide-treated 14 and 18 days old embryos and in those of the corresponding controls. Immunocytochemical studies of the pituitary of 18 days old embryos revealed a depletion of immunoreactive TSH suggesting that the iodide-induced hypertrophy of the thyroid was mediated by an activation of the thyrotropes. Iodide treatment was without effect on plasma levels of T3 and T4 for Day 18 embryos suggesting that the compensatory hypertrophy of the thyroid gland was sufficient to maintain circulating levels of thyroid hormones. The present results demonstrate that, in the embryonic chick thyroid, excess iodine produces effects which occur in two phases. The first phase consists of a transitory inhibition of the formation of follicles; it is followed by a second phase of compensatory hypertrophy resulting in goitre. The first phase probably results from a direct inhibitory effect of iodine on the developing thyroid whereas the second phase probably reflects a stimulation of the thyroid by TSH. PMID- 1917669 TI - Morphometry of the human thigh muscles. A comparison between anatomical sections and computer tomographic and magnetic resonance images. AB - The present study examined the relative accuracy and precision of MR and CT procedures for determining the CSA of individual muscles from the human thigh. Serial AN, CT and MR cross-sections were obtained from three cadaveric lower limbs. The MR measurements provided accurate and precise values for the CSAs of most thigh muscles, generally within +/- 7.5% of the AN standard. In contrast, CT tended systematically to overestimate the AN CSA by 10-20%. Retest procedures indicated that highly reliable measurements could be obtained from both MR and CT images. However, subjective interpretations of boundaries between closely apposed muscle bellies, particularly for muscles with more than one head, were necessary for resolving entities in the imaging records and this decreased the relative accuracy of MR and CT measures. Interestingly, MR records demonstrated an incomplete septum between vastus lateralis and vastus intermedius more prominently than AN cross-sections. The novel cross-validation procedures used in this study also highlighted several system-based errors in the MR records that, if undetected and left uncorrected, would have seriously biased the morphometric data obtained with this technique. In general, MR provides high resolution images of the human thigh muscles which may be used to obtain valid measures of the CSA of these structures. PMID- 1917671 TI - Reinnervation of developing rat molars. AB - The ability of regenerating inferior alveolar nerve (IAN) fibres to reinnervate dentine of developing rat first molar teeth was investigated. At intervals of 5, 15, 30 and 50 days after intramandibular transection of the IAN at the age of 20 days, the percentage of innervated dentinal tubules was estimated and compared with results from a series of control specimens. In addition, the myelinated axon populations of the root canal pulps were examined by light microscopy. Degeneration of almost all pulpal myelinated axons and dentinal unmyelinated axons occurred within 5 days of surgery. By 15 days after transection there was evidence of some pulpal reinnervation by myelinated axons but less than 2% of dentinal tubules showed reinnervation (control, 31.8%). At 30 days after surgery the figure for dentinal reinnervation was approximately 17.7% (control, 44.9%), and by 50 days after transection (70 days of age) mean innervation was about 70% of the level observed in control 70 days teeth, though the difference between control and experimental specimens was not significant at the 5% level of probability. The results indicate that reinnervation of dentine does occur in developing teeth after nerve transection. It is argued that the results suggest a faster and probably more complete reinnervation in young animals; and that reinnervation may be attributable more to an active than to a passive mechanism, and this may also apply to dentinal innervation during development. PMID- 1917672 TI - Intracellular production of adrenal renin in the fetal mouse. An immuno-electron microscopical study. AB - Renin-containing cells in fetal adrenal glands of the mouse were investigated with the protein A-gold immunocytochemical technique. On Day 14 of gestation, a small number of specific granules were weakly immunoreactive and were distributed in the Golgi region. Sometimes, apparent exocytosis of gold-labelled particles could be seen opening into the extracellular space. On Day 16 of gestation, numerous gold particles were demonstrated in the Golgi region as well as in the specific secretory granules. Immunoreactivity of the specific granules was increased as compared with Day 14, though some granules were observed to have no reaction with the antibody. On Day 18 of gestation reactivity for renin decreased, while a few clustered immunoreactive granules were demonstrated just beneath the cell membrane. No gold particles were observed in the Golgi apparatus during this period and more granules negative for renin were noted than on Day 16 of gestation. These results suggest that renin is produced and released temporarily by adrenal cortical cells in the late fetal life of the mouse. PMID- 1917673 TI - The response of the regional lymph node to epididymal sperm granulomas after vasectomy. AB - The cause of the variable immune response in the regional testicular lymph node of inbred Albino Swiss rats after vasectomy was investigated in two experiments. In the first, the ductus deferens was transected at its junction with the epididymis so that, in every case, sperm granulomas developed in the epididymis, from which lymph is known to drain invariably to the testicular node. In spite of this, not all testicular nodes showed histological signs of an immune response at 12 weeks after vasectomy. In the second experiment the contents of epididymal lymphatics were compared in vasectomised rats and sham-operated controls at intervals of up to 18 months after operation. Lymphatics in animals with an 'active' epididymal granuloma invariably contained numbers of macrophages and lymphocytes, thought to be involved in antigen transport, while those of controls contained none. It is concluded that variations in the lymphatic drainage of vasal granulomas were not primarily responsible for the variable lymph node response to vasectomy previously reported. PMID- 1917674 TI - A comparative study of the circle of Willis in fetal and adult life. The configuration of the posterior bifurcation of the posterior communicating artery. AB - The configuration of the posterior bifurcation of the posterior communicating artery is commonly described as the 'adult configuration' if the diameter of the precommunicating part of the posterior cerebral artery (P1) is larger than the diameter of the posterior communicating artery itself (PCA). In these cases the blood supply to the occipital lobes is mainly from the vertebro-basilar system. Only in a minority of cases is the fetal or embryonic configuration found. Here the diameter of the PCA is larger than the diameter of the P1 and the blood supply to the occipital lobes is mainly from the internal carotid artery via the posterior communicating artery. In order to track the origin of these different configurations, 53 complete circles of Willis (106 sides) in brains of fetuses and infants aged from 12 weeks to 60 weeks after conception were examined with the aid of an operating microscope, and measurements were made of the diameters of the PCA, P1 and P2. It is concluded that the variations of this part of the circle of Willis are the result of developmental modifications. This is confirmed by a statistical analysis that shows a relation between the stage of development of the brain and the occurrence of the different configurations. The frequencies of the adult and fetal configurations gradually increase at the expense of the transitional configurations. This configuration is found early in development and is characterised by the equality of the diameters of the PCA and P1. These findings contradict the views, found in the literature, that the variations either exist early in development as a consequence of genetic factors or arise after birth as a consequence of mechanical genetic factors. PMID- 1917675 TI - Thyroid morphology and function and its role in thermoregulation in the newborn southern elephant seal (Mirounga leonina) at Macquarie Island. AB - The thyroid gland of the newborn southern elephant seal pup exhibits markedly increased secretory activity during the first 24 hours after birth. Thyroid epithelial cell height is cuboidal to columnar for pups from birth to 48 hours postpartum after which it decreases by five days of age. Ultrastructurally the thyroid epithelial cells show pseudopodia protruding into the lumen at zero, two and six hours after birth. After 24 hours postpartum pseudopodia are rarely observed in thyroid follicles from two to 20 days old pups. The number of colloid droplets increases by six hours after birth and they are distributed throughout the cytoplasm. At 24 hours and two days, few colloid droplets are observed. Plasma T4 concentration increases three-fold from birth, to peak at six hours postpartum after which it steadily declines. Plasma concentration of T3 increases eight-fold between birth and 24 hours postpartum. T3 levels remain high until five days to seven days, then decrease to 20 days. The observed changes in thyroid epithelial cell height and ultrastructure is strongly suggestive of increased secretion of thyroid hormones during the first six hours of postnatal life. This pattern of thyroid activity is similar to that in other newborn mammals which have been examined. The thyroid gland of the southern elephant seal is markedly active at birth and is responsible for the elevated levels of T4 and T3, thus playing a vital role in maintaining the body temperature of the newborn seal when it enters the harsh environment of the sub-Antarctic. PMID- 1917676 TI - The effects of disorders of cartilage formation and bone resorption on bone shape: a study with chondrodystrophic and osteopetrotic mouse mutants. AB - The shapes of scapulae and basi-occipital bones from three genetically distinct achondroplastic mutants and one osteopetrotic mutant in the mouse (achondroplasia, brachymorphic, stumpy and grey lethal), and appropriate controls, have been compared using Fourier analysis and multivariate statistical techniques. Normal littermates were generally similar in shape, but mutants were significantly different from these controls and from each other. The pattern of morphological differences between the mutants and between the mutants and normal controls is examined. These differences are discussed in relation to the different effects of the four genes on bone morphogenesis, and the significance of these findings in relation to the contributions of cartilage formation and bone resorption to skeletal morphogenesis is considered. PMID- 1917677 TI - Adaptations of the rat small intestine to a single and a double period of undernutrition. AB - Male rats were undernourished from birth to 3 weeks of age and then allowed a period of unrestricted access to food. These animals were subjected to a second period of undernutrition from 9 to 12 weeks. A group of rats undernourished from 9 to 12 weeks only, and a group well-fed throughout life were used for comparison. Six rats from each group were anaesthetised by intraperitoneal injection with sodium pentobarbitone and killed by perfusion with glutaraldehyde at 12 weeks of age and the small intestine removed and its length recorded. Resin embedded sections 1 micron thick were cut in the transverse plane from proximal and distal regions of each intestine. Point and intersection counting was performed to estimate villous surface area, volume and shape as well as crypt and muscle volume. The body weight of the undernourished rats was significantly (P less than 0.01) reduced compared to controls, with doubly undernourished rats weighing significantly (P less than 0.05) less than singly deprived animals. Rats undernourished once showed larger deficits in villous surface area and volume in distal regions than in proximal ones. However, in rats undernourished during the weaning period and again in later life the proximal part also became affected, while the distal region was not affected further. Therefore, it appears that the distal region of the rat small intestine is more vulnerable to a single period of food restriction during adult life than is the proximal part. PMID- 1917678 TI - Tail fin regeneration in teleosts: cell-extracellular matrix interaction in blastemal differentiation. AB - The fins of teleosts are appendices capable of regenerating by an epimorphic process that completely restores in a few days the original shape and size. After a partial amputation, the process that follows consists of: wound healing, blastema formation and cell differentiation to form a particular cell population responsible for the building of the different tissue elements. The present work deals with the histochemical and ultrastructural characterisation of the extracellular matrix (ECM) components in different blastemal regions. In the subepidermal space of the tip of a regenerating ray, two zones can be identified: the blastema proper (BP) that occupies the more apical region and extends proximally along the centre of the regenerating ray, and the actinotrichial blastemic region (ABR), located laterally to the former, about some micrometres beneath the tip and tightly related with the palisade of the actinotrichia. Hyaluronate is the more prominent glycosaminoglycan (GAG) in BP whereas sulphated GAGs and collagen are scarce in distal portions but they can be identified proximally. In the ABR a network composed mainly of sulphated GAGs and in part of collagen is developed. This network connects the actinotrichia of each palisade and extends around them. The significance of the ECM components in the morphogenetic processes of the regenerating rays is discussed. In addition a model for the synthesis of lepidotrichia by lepidotrichium-forming cells, differentiated from blastemal cells, is given. PMID- 1917679 TI - Ontogeny of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta HSD) in human testis as studied by immunocytochemistry. AB - The enzyme complex 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) is involved in the biosynthesis of all classes of active steroids, including androgens. To correlate possible changes in 3 beta-HSD with the well-known variations in testosterone secretion during development, the authors localized this enzyme by immunocytochemistry during fetal and postnatal periods of development in the human testis. In the fetal testis, 3 beta-HSD was detected in Leydig cells during the second and third trimester of gestation. In 8 month-old and 11-year-old boys, however, no immunoreaction could be detected in the testis. In pubertal boys, Leydig cells appeared well developed and immunopositive. Since the fluctuations in 3 beta-HSD immunoreactivity are similar to those already observed for androgen secretion, activation of 3 beta-HSD by trophic hormones may play an important role in androgen production during fetal and postnatal development. PMID- 1917680 TI - The application of pentoxifylline in the stimulation of sperm motion in men undergoing electroejaculation. AB - The ability of pentoxifylline to stimulate the motion characteristics of antegrade and retrograde sperm collected at the time of electroejaculation with a rectal probe was assessed in six neurologically impaired men. Before electroejaculation, the bladder was rinsed and instilled with 20 to 30 ml Ham's F 10 medium. Washed sperm were incubated with various doses (0, 0.1, 1, and 3 mmol/L) of pentoxifylline. Video sequences were recorded at intervals from 0 to 4.5 hours and analyzed for sperm motion parameters using manual and computer assisted semen analysis. The results were compared with equimolar concentrations of caffeine. Both pentoxifylline and caffeine demonstrated a dose-dependent stimulation of percent motility and other motion parameters. A maximal stimulation of two-fold to three-fold for both percent motility and curvilinear velocity, and 30% to 60% for straight line velocity was observed after incubation under these conditions. A significant increase in mean linearity was observed in samples incubated with 0.1 mmol/L pentoxifylline at 1.5 hours. Significant lateral head displacement was not observed at any time point. Two couples underwent gamete intrafallopian transfer (GIFT) in conjunction with this electroejaculation sperm stimulation procedure, and one has since delivered a normal child. These studies show that pentoxifylline stimulation can improve the movement characteristics of asthenospermic sperm from neurologically impaired men. Such sperm stimulation techniques do not affect the fertilization process and may improve the chances for conception in some cases of male-factor infertility. PMID- 1917681 TI - Assessment of the hypothalamic-pituitary-testicular function in male patients with Wilson's disease. AB - Sixteen male patients with Wilson's disease were studied to detect potential endocrine dysfunctions. There was no clinical evidence of feminization in any of the patients, and the patient group spanned most pubertal stages. Gonadotropin, testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate, androstenedione, estradiol, prolactin, cortisol, thyrotropin, and free thyroxine levels were determined. Low or borderline luteinizing hormone (LH) levels were present in most of the patients. In six of the adult patients, a standard gonadotropin-releasing hormone (GnRH) test was performed. Five of the six patients had blunted LH and follicle-stimulating hormone (FSH) responses to GnRH. Increased androgen levels were found in eight of the patients. Sex hormone binding globulin was normal in eight of nine tested patients. Three single-dose human chorionic gonadotropin (hCG) stimulation tests of six adult patients showed normal responses. Three other patients who had elevated baseline levels responded with modest increases. Since liver disease is usually associated with decreased androgen levels, it is difficult to account for the elevated androgen levels. Both increased androgen levels and copper accumulation in the hypophysis could be responsible for the blunted GnRH response. PMID- 1917682 TI - Diurnal rhythm of testosterone and luteinizing hormone in hypogonadal men. AB - To determine the relationship between increasing luteinizing hormone (LH) production and the diurnal secretion of LH and testosterone (T) in adult men, studies were performed on five men with gonadotropin insufficiency associated with prolactinoma, five eugonadal men, and five men with primary testicular failure. Blood samples were drawn every 10 to 20 minutes for 24 hours beginning at 8:00 to 8:30 AM to evaluate diurnal periodicity. Mean (+/- SEM) LH levels in the three groups were 7.67 +/- 1.46 mlU/ml, 13.9 +/- 3.2 mlU/ml, and 62.3 +/- 14.4 mlU/ml, respectively, and mean serum T levels were 8.05 +/- 1.49 nmol/L, 13.9 +/- 3.5 nmol/L, and 9.15 +/- 1.3 nmol/L, respectively. Cosinor analysis revealed that each hyperprolactinemic man had a T rhythm with a significant 24 hour periodicity; the mean acrophase was at 5:00 AM. Testosterone levels were 35.0 +/- 10.6% less at 4:00 PM than at 8:00 AM. Eugonadal men also demonstrated a significant diurnal T rhythm with an acrophase at 6:00 AM, and T levels were 15.8 +/- 5.3% less at 4:00 PM than at 8:00 AM. By contrast, there was no significant diurnal rhythm in T secretion among the men with testicular failure, although serum T levels were 11.5 +/- 3.7% less at 4:00 PM than at 8:00 AM. For LH, hyperprolactinemic men demonstrated a significant 24-hour rhythm with an acrophase at 1:30 AM, whereas no significant 24-hour periodicity was identified among either eugonadal men or men with testicular failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917683 TI - Relative ratios of lactoferrin, albumin, and acid phosphatase seminal levels as sperm quality markers in fertile and infertile men. AB - Human seminal plasma proteins from fertile and infertile men were fractionated by electrophoresis. The amounts of three Coomassie-stained protein bands were measured by densitometry. Their relative ratios were constant in normospermic men but varied in the infertile patients. Laboratory manipulation of the semen was shown not to affect the protein ratios as observed after liquefaction, incubation at various temperatures, and storage at -20 degrees C. The three proteins were purified by chromatographic techniques and identified as lactoferrin, albumin, and acid phosphatase by electrophoresis, high-pressure liquid chromatography, and enzyme assays. The use of these proteins to evaluate the contributions of different fluids to seminal plasma is discussed. PMID- 1917684 TI - S-adenosyl-L-methionine decarboxylase activity in the rat epididymis: ontogeny and androgenic control. AB - The authors describe the occurrence of high levels of S-adenosyl-L-methionine decarboxylase (SAMDC) activity in the rat epididymis, and its ontogeny and androgenic control. As early as 15 days of age, SAMDC activity exists, although a peak of activity is observed at 25 days. Bilateral orchidectomy resulted in a decline of epididymal SAMDC activity. However, an androgen-independent fraction, accounting for 34% of total activity, appears to exist in the epididymis. In 45 day-old orchidectomized rats, SAMDC activity was stimulated by testosterone treatment in a dose-dependent manner. However, treatment of 45-day-old intact animals with a high dose of the androgen failed to modify SAMDC activity, indicating that, at this age, the enzyme is maximally stimulated by endogenous androgens. The observed effect of testosterone on castrated rats was completely abolished by concomitant treatment with the antiandrogen flutamide. This compound was ineffective on the androgen-insensitive fraction. To assess the contribution of circulating and luminal androgens to the maintenance of epididymal SAMDC, rats were unilaterally orchidectomized and activity was determined in both epididymides after 7 days. The SAMDC activity was identical in epididymides from both sides, suggesting circulating androgens suffice to maintain normal levels of activity. It was concluded that androgens regulate epididymal SAMDC activity, although an androgen-independent fraction appears to exist. PMID- 1917685 TI - Collection and analysis of semen from the common marmoset (Callithrix jacchus). AB - The authors examined the seminal characteristics of 16 male common marmosets (Callithrix jacchus) to provide baseline data for future studies of the reproductive biology of this species. Semen samples were collected by electroejaculation. There was considerable inter- and intra-male variation in all seminal characteristics. The median seminal volume was 30 microliters (range 8 to 85 microliters), and the median total sperm count was 5.1 x 10(6) sperm (range, 0.1 to 43 x 10(6]. The median progressive sperm motility was 48% (range, 10% to 76%), and 49% of the sperm exhibited normal morphology (range, 24% to 81%). Three types of sperm head abnormalities and eight types of tail defects were noted. Tail defects were common (median, 50%; range, 17% to 76%), whereas head defects were relatively rare (median, 4.5%; range, 0% to 24%). The results indicate that semen samples can be routinely collected from this species, but considerable inter- and intra-male variation can be expected. It is therefore important to examine several semen samples from each male marmoset to obtain an accurate seminal picture. PMID- 1917686 TI - Effects of follicular fluid administration on serum bioactive and immunoreactive FSH concentrations and compensatory testosterone secretion in hemicastrated adult rats. AB - In adult rats, removal of one testis (hemicastration) results in an elevation of serum follicle-stimulating hormone (FSH) concentrations and a compensation in testosterone secretion by the remaining testis without a corresponding increase in testis size. To determine whether changes in FSH secretion and compensatory androgen production are related, serum testosterone concentrations were measured after inhibin-rich porcine follicular fluid was administered twice daily for 4 days to block the hemicastration-induced rise in FSH. Both serum immunoreactive FSH (immuno-FSH) and bioactive FSH (bio-FSH) concentrations were increased 4 days after hemicastration. The significant increase in serum immuno-FSH in hemicastrated animals was prevented by follicular fluid administration, whereas the serum bio-FSH activity and biologic to immunologic (B/I) ratios were increased in follicular fluid-treated animals. The follicular fluid-induced reduction in serum immuno-FSH had no effect on serum testosterone secretion in hemicastrated rats. Serum inhibin concentrations were reduced 27% in hemicastrated rats compared with intact controls, while administration of exogenous follicular fluid increased serum inhibin concentrations. An elevation in serum immuno-FSH secretion after hemicastration apparently is not required for the compensatory testosterone response. However, the observation of increased bio FSH in hemicastrated and follicular fluid-treated animals raises questions about the importance of FSH quality (bioactivity), rather than quantity, for controlling testicular steroidogenic activity. PMID- 1917687 TI - Hypergonadotropic hypogonadism and sperm abnormalities in men born with benign sacrococcygeal teratoma. AB - To elucidate the hypothetical role of a primary germ cell defect in the development of a germ cell tumor, with subsequent testicular dysfunction, the authors studied a series of men who had surgery performed for a benign sacrococcygeal teratoma when newborns. The mean levels of serum testosterone and gonadotropins did not differ from the control patients. However, gonadotropin releasing hormone stimulation caused exaggerated responses of serum luteinizing hormone and follicle-stimulating hormone. Testicular size was small in three of eight patients. Semen analysis showed abnormal semen quality in five of eight patients. Only one patient had no evidence of testicular dysfunction. The results indicate that men born with benign sacrococcygeal teratoma may have Leydig cell dysfunction, abnormal spermatogenesis, or both. It was speculated that the associated abnormalities may have a common etiology: for instance, they might be due to a congenital germ cell defect. PMID- 1917688 TI - Relationship between sperm motility assessed with the Hamilton-Thorn motility analyzer and fertilization rates in vitro. AB - To determine which sperm movement characteristics are related to in vitro fertilization rates, semen and swim-up preparations used for in vitro fertilization in 108 patients were assessed using the Hamilton-Thorn HTM-2030 Motility Analyzer (HTMA) and other sperm tests. There were highly significant correlations between manual and HTMA results for sperm concentration (Spearman r = 0.881; P less than 0.001) and the percentage of motile spermatozoa (Spearman r = 0.580; P less than 0.001). The percentage of motile spermatozoa with average path velocities greater than 10 microns/s and greater than 20 microns/s, straight line and curvilinear velocity, linearity (straight line velocity vs curvilinear velocity), amplitude of lateral head displacement, and beat-cross frequency were significantly higher in the insemination medium after selection of motile spermatozoa by the swim-up technique than in the semen. Linearity (P less than 0.01), the percentage of morphologically normal spermatozoa (P less than 0.05) and straight line velocity (P less than 0.05) in semen, and the percentage of motile spermatozoa with average path velocities greater than 10 microns/s in both semen (P less than 0.05) and insemination medium (P less than 0.05) were significantly correlated with in vitro fertilization rate when examined by a nonparametric (Spearman) test. With logistic regression analysis of all data, only the diagnoses of male infertility and tubal disease, linearity in semen, and the percentage of motile spermatozoa with average path velocities between 10 and 20 microns/s in insemination medium were significantly related to in vitro fertilization rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917689 TI - Mitosis in normal adult guinea pig Leydig cells. AB - In this study, Leydig cells in mitosis in adult guinea pigs were quantified. Testes of adult control guinea pigs (n = 10) were fixed by whole body perfusion with 2.5% glutaraldehyde in cacodylate buffer, postfixed in a mixture of osmium tetroxide-potassium ferrocyanide, and embedded in Epon Araldite for qualitative and quantitative microscopy. Using stereologic techniques, the total number of Leydig cells per testis and the number of dividing Leydig cells per testis were quantified. Light microscopic studies revealed the presence of dividing Leydig cells. Ultrastructural studies on a few of these Leydig cells showed that they contained abundant smooth endoplasmic reticulum and mitochondria, which further supported this identity. The total number of Leydig cells per testis and the number of dividing Leydig cells per testis were determined as 14.1 x 10(6) (standard error [SE] = 0.33) and 8 x 10(3) (SE = 5), respectively. These results indicate that Leydig cells undergo mitosis at a rate of 1 per 1.75 x 10(4) in adult guinea pigs. PMID- 1917690 TI - Influence of bovine follicular and oviduct fluids on sperm capacitation in vitro. AB - The ability of bovine follicular fluid (FF) and oviduct fluid (ODF) to capacitate sperm was determined. At concentrations of greater than 20%, both FF and ODF capacitated sperm within 4 hours, but at concentrations greater than 40%, FF also initiated the acrosome reaction. Non-luteal ODF at a concentration greater than 60% capacitated sperm within 2 hours. Non-luteal ODF maintained sperm motility better than either luteal ODF or FF. Sperm previously capacitated in ODF underwent the acrosome reaction when exposed to solubilized zonae pellucidae (25 ng/microL) or FF (20%, V/V). Sperm treated with 60% non-luteal ODF or 60% FF fertilized more oocytes at 2 hours than did sperm in treatments with less concentrated fluid. After 4 hours, all fluid treatments and modified Tyrode's medium supplemented with heparin exhibited a higher percentage of fertilized oocytes than the modified Tyrode's medium alone. Concentrations of both protein and glycosaminoglycans were significantly lower in ODF than in either blood serum or FF. These studies demonstrated that ODF capacitated sperm and sustained motility, but sperm were capacitated more rapidly in non-luteal than in luteal ODF. In contrast, FF was able to both capacitate sperm and induce the acrosome reaction. These effects of ODF and FF on aspects of sperm function were uniquely concentration-dependent, suggesting that different mechanisms may operate in ODF and FF to regulate these events. PMID- 1917691 TI - Evaluation of human sperm hyperactivated motility and its relationship with the zona-free hamster oocyte sperm penetration assay. AB - The authors studied hyperactivated motility of human spermatozoa as a method of evaluating capacitation by examining its relationship to results of zona-free hamster oocyte sperm penetration assays (SPA) of semen samples from 50 men attending the infertility clinic. Hyperactivated motility was assessed in the seminal plasma and after swim-up preparation of spermatozoa at 1, 3, and 24 hours of incubation in capacitation media using a computer-assisted semen analysis system equipped with a hyperactivation module. Hyperactivated motility reached a peak at 1 hour and plateaued at 3 hours. The percentage of spermatozoa in seminal plasma with star-spin hyperactivated motility was significantly lower in the group showing no penetration in the SPA. The hyperactivated motility characteristics did not differ in the groups with positive or negative penetration. Correlation analysis failed to show any significant relationship between the hyperactivated motility parameters and SPA score. When the hyperactivated motility characteristics were compared in samples with normal and abnormal semen analyses, the total percentage of spermatozoa with hyperactivated motility and the percentage with star-spin at 3 hours were significantly lower in the group with abnormal semen analysis. The data indicate that lower hyperactivated motility of spermatozoa was found in patients with a score of zero for SPA and in patients with abnormal semen analysis. It was concluded that although no direct correlations were found between the results of SPA and hyperactivated motility, evaluating hyperactivated motility may still be useful as an early indicator of capacitation abnormalities of human spermatozoa not measured by SPA. PMID- 1917692 TI - The effects of normal aging on the response of the pituitary-gonadal axis to chronic clomiphene administration in men. AB - Serum androgens decline with age in normal men, despite normal or elevated bioactive serum gonadotropins, suggesting that primary testicular dysfunction occurs with aging. The authors further assessed the question of age-related testicular dysfunction by evaluating whether raising serum gonadotropins above the normal serum range for an extended time in healthy elderly men might result in bringing their gonadal function to a level similar to that found in young adult men. Five elderly (65 to 85 years old) and five young adult men (26 to 33 years old) were given 50 mg of clomiphene citrate (CC) twice a day for 8 weeks to stimulate gonadotropin production. During that time, testosterone (T), non-sex hormone-binding globulin bound T, and estradiol increased significantly in both age groups, while serum inhibin increased significantly only in the young adult men. The increases in serum androgens with CC administration were significantly greater in the young adult men than in the elderly men. These hormone changes occurred in the setting of serum gonadotropins that increased significantly in both age groups, although there was a tendency for the elderly men to have a smaller increase in luteinizing hormone. Despite 8 weeks of stimulation of the pituitary-gonadal axis by CC administration, the elderly men demonstrated significantly diminished testicular responses compared with the young adult men. Sertoli cell function, as determined by inhibin production, was more diminished in the elderly men than was Leydig cell function. These data strengthen the hypothesis that normal aging in men is accompanied by a decline in testicular function. PMID- 1917694 TI - MM 55266 and MM 55268, glycopeptide antibiotics produced by a new strain of Amycolatopsis. Isolation, purification and structure determination. AB - Two novel glycopeptide antibiotics MM 55266 and MM 55268 containing fatty acid acyl functions, and of molecular formula C86H89N8O35Cl5 and C87H91N8O35Cl5, respectively, have been isolated and identified from a complex produced by Amycolatopsis sp. NCIB 40089. Fermentation conditions for their production, and methods for their isolation are described. Structures have been deduced by use of COSY and NOE NMR techniques and supported by chemical degradation studies. Both glycopeptides possessed good antibacterial activity against Gram-positive organisms. PMID- 1917693 TI - Pituitary regulation of the expression of the farnesyl pyrophosphate synthetase gene in the testes of the sexually maturing rat. AB - While investigating the coordinate regulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and farnesyl pyrophosphate synthetase, the authors observed that rat testes contained high levels of a farnesyl pyrophosphate synthetase mRNA that was larger than that found in most other tissues. This mRNA contains upstream AUG codons that may alter its rate of translation. The developmental and hormonal regulation of this testicular mRNA were investigated. Testicular levels of farnesyl pyrophosphate synthetase mRNA increased in rats between 30 and 40 days of age and remained elevated. Significant increases in serum testosterone concentrations and secondary sexual organ weights first occurred at 50 days of age. Hypophysectomy resulted in nearly undetectable levels of testicular farnesyl pyrophosphate synthetase mRNA. Treatment of hypophysectomized rats with gonadotropins increased the levels of this mRNA toward normal. These data indicate that an increase in farnesyl pyrophosphate synthetase mRNA takes place in testes just before the onset of puberty. This may be induced by the peripubertal rise in follicle-stimulating hormone. PMID- 1917695 TI - A new antibiotic, okicenone. I. Taxonomy, fermentation, isolation and biological characteristics. AB - A new antibiotic, okicenone was isolated from the culture broth of Streptomyces sp. KO-3599. The antibiotic possesses cytocidal activity against mammalian tumor cells in vitro at concentrations of 0.53-11.0 micrograms/ml whereas the antibiotic showed no antimicrobial activities against Gram-positive and Gram negative bacteria, fungi or yeast at a concentration of 1,000 micrograms/ml. PMID- 1917696 TI - A new antibiotic, okicenone. II. Physico-chemical properties and structure elucidation. PMID- 1917697 TI - A novel hepatoprotective gamma-lactone, MH-031. I. Discovery, isolation, physico chemical properties and structural elucidation. PMID- 1917698 TI - The structure of heneicomycin. AB - The antibiotic heneicomycin (1), C44H62N2O11, was isolated from cultures of Streptomyces filipinensis as an amorphous yellow powder. Mass spectral and NMR analysis showed the compound to be a deoxy modification of aurodox (2), a member of the elfamycin antibiotic family. A marked change in mass spectral fragmentation compared to aurodox and 1H NMR couplings indicated the absence of the hydroxyl at position 30 of aurodox (position 3 of the tetrahydropyran). PMID- 1917699 TI - Antibacterial activity of 5-acylaminothiazole derivatives, synthetic drugs related to beta-lactam antibiotics. AB - Newly synthesized 5-acylaminothiazolium salts and one 5-acylaminothiazolidine, considering their chemical structure and reactivity, have been proposed as potential inhibitors of bacterial serine DD-peptidases. A moderate antibiotic activity with (5-phenylacetylamino-3-thiazolio)acetate and (5 phenylacetylaminothiazolidin-3-yl)acetic acid was observed on Staphylococcus aureus ATCC 25923. The methyl- and tert-butyl esters of the thiazolium salt have shown lower MIC values. Moreover, when introduced into an exponential growth phase culture of S. aureus, the three active thiazolium salts induced a partial lysis indicating an impairing of the bacterial cell wall biosynthesis. The observed time-dependent binding of the best compound to the PBPs of S. aureus was too slow and occurred at too high concentrations to account for its MIC value. Consequently, the antibiotic activity of the thiazolium salts on the S. aureus cells seems not to be satisfactorily explained by a penicillin-like interaction with the PBPs. PMID- 1917700 TI - Cephalosporin antibiotics. I. Synthesis and structure-activity relationships of 3 thiazoliomethyl derivatives. AB - The synthesis and the structure-activity relationships of 3-thiazoliomethyl cephalosporins are described. In a series of these parenteral compounds, 2-(2 aminothiazol-4-yl)-(Z)-2-methoxy-iminoacetamido group was found to be a favorable substituent for the C-7 position of the cephem nucleus. They showed potent antibacterial activity against both Gram-positive and Gram-negative bacteria including some beta-lactamase producing species. PMID- 1917701 TI - Cephalosporin antibiotics. II. Synthesis and biological properties of CS-461 and related compounds. AB - The synthesis, structure-activity relationships, and biological properties of 3 thiazoliomethyl cephalosporins are described. 7-[2-(2-Aminothiazol-4-yl)-(Z)-2- methoxyiminoacetamido]-3-[5-(2-hydroxyethyl)-4-methylthiazoliomethyl+ ++]-3- cephem-4-carboxylate sulfate (CS-461) showed potent antibacterial activity against a wide variety of bacteria both in vitro and in vivo. Furthermore, CS-461 exhibited significantly low acute toxicity in mice. PMID- 1917702 TI - Naphthyridinomycin-DNA adducts: a molecular modeling study. AB - Monocovalent groove binding complexes of antitumor antibiotic naphthyridinomycin and its analogs with DNA sequence d(ATGCAT)2 have been studied by molecular mechanics to understand which enantiomer of the drug and what chirality at C(7) of the drug are preferred for forming better drug-DNA adducts. The effect of hydroquinone intermediate and the substitution at C(11) on drug-DNA interactions have also been investigated. The results indicate that the enantiomer that forms the best adduct is different from the one reported earlier in the literature. The drug with an R configuration at C(7) is preferred for binding. The hydroquinone models do not necessarily provide a given analog of the drug with additional favorable DNA interactions. The substitution at C(11) by OH provides the best binding model. This finding agrees well with the results from previous biochemical studies. The sequence specific studies indicate that the sequence d(ATGCAT)2 is slightly preferred over others. PMID- 1917703 TI - Total synthesis and biological evaluation of unnatural (-)-medermycin [(-) lactoquinomycin]. PMID- 1917705 TI - Novel antitumor antibiotics, saptomycins D and E. PMID- 1917704 TI - Studies on free radical scavenging substances from microorganisms. II. Neocarazostatins A, B and C, novel free radical scavengers. PMID- 1917706 TI - Syntheses and enzyme inhibiting activities of cyclophellitol analogs. PMID- 1917707 TI - Inhibition of epidermal growth factor-induced activation of phospholipase C by psi-tectorigenin. PMID- 1917708 TI - Low-frequency component of the gerbil brainstem response: response characteristics and anesthesia effects. AB - The auditory brainstem response (ABR) was recorded with epidural electrodes in awake and anesthetized gerbils. Low- and high-frequency components of the ABR were separated by analog filters and compared as functions of stimulus intensity, frequency, repetition rate, and effects of anesthesia. In response to 0.5 kHz tone bursts, thresholds of the low-frequency component (LF-ABR) were significantly lower than that of the most prominent peak of the high-frequency components (wave P4). At both 2 and 4 kHz, thresholds of the LF-ABR and wave P4 were not significantly different. Changes in stimulus intensity over a 70 dB range produced similar changes in peak amplitudes and latencies for the LF-ABR and P4. However, while the amplitude of the LF-ABR was inversely related to stimulus frequency, the amplitude of P4 was reduced at 0.5 kHz, as compared to 2 and 4 kHz. Increases in stimulus rate from 7 to 100 bursts/s produced little change in the amplitude of the LF-ABR. At rates of 80 and 100 bursts/s, the LF ABR was sinusoidal in appearance due to the proximity of successively generated potentials. In contrast, the amplitude of P4 varied inversely with stimulus rate between 20 and 100 bursts/s. Administration of ketamine and xylazine produced minor changes in the amplitudes and latencies of both the LF-ABR and wave P4. The response characteristics of the gerbil LF-ABR are similar to those of the low frequency component of the ABR in humans and cats. The LF-ABR provides an estimate of hearing threshold at low frequencies (0.5 kHz) as well as higher frequencies (2-4 kHz). A major advantage to the LF-ABR is that it can be recorded at high stimulation rates in awake and anesthetized animals, thus providing an efficient measure of auditory function. PMID- 1917709 TI - A cochlear model using feedback from motile outer hair cells. AB - A model of cochlear vibrations based upon motile outer hair cells (OHCs) has been developed using physiologically demonstrated phenomena. Rapid longitudinally directed OHC forces are connected in such a way as to form a negative-feedback system. The responses at the higher frequencies (greater than 1 kHZ) are quite realistic: they have properly shaped amplitude curves with large tip-to-tail ratios (30-50 dB), Q10's of 2-6, and 'shoulders' at frequencies an octave below the resonant frequency. The phases are also quite realistic, though asymptoting at somewhat lower values (about -6 pi radians) than observed physiologically. The responses in the apical section are not so realistic. The form of the OHC force is physically unrealizable, but realizable forms are discussed. PMID- 1917710 TI - Reorganization of auditory cortex after neonatal high frequency cochlear hearing loss. AB - Cochleotopic representation in cortex (AI) is extensively reorganized in cats having neonatal, bilateral high frequency cochlear hearing loss. Anterior areas of AI, normally devoted to high frequencies, contain neurons which are almost all tuned to one lower frequency. This frequency corresponds, at the level of the cochlea, to the border between normal and damaged haircell regions. PMID- 1917711 TI - The ionic and electric environment in the endolymphatic sac of the chinchilla: relevance to the longitudinal flow. AB - The ionic composition of the endolymph in the endolymphatic sac (ES) of the chinchilla was measured using double-barreled ion-selective micro-electrodes. The DC potential of the ES was 9.3 +/- 1.8 mV (N = 18). The K+, Na+, and Cl- concentrations of the ES were 13.3 +/- 4.7 mM (N = 6), 129.0 +/- 8.8 mM (N = 6), and 124.3 +/- 16.6 mM (N = 6), respectively. In light of the chemical potentials of the cochlear endolymph previously reported [Ikeda and Morizono (1989), Hear. Res., 39, 279-286] the pressure gradient of the endolymph between the cochlea and ES was calculated to be 71.5 mmHg at 38 degrees C. The contribution of the osmotic and hydrostatic pressure gradients of the endolymph to the longitudinal flow is discussed. PMID- 1917712 TI - Age-related changes in cochleas of mongolian gerbils. AB - The effects of aging on the gerbil cochlea were studied in 16 animals raised in a quiet environment. Animals were tested at ages ranging from 33 to 36 months, the approximate average lifespan of gerbils in our colony. Hearing sensitivity was assessed by measures of whole-nerve compound action potential (CAP) thresholds and surface preparations of the organ of Corti were subsequently examined by light microscopy for losses of sensory hair cells. These quiet-aged animals showed a wide range of hair-cell losses and threshold shifts. Outer hair cells often showed significant losses while inner hair cells were rarely absent. All animals had some threshold shift, especially at frequencies above 4 kHz. These shifts ranged from 1 to 68 dB. At high frequencies, threshold shifts often occurred without hair-cell losses at corresponding cochlear locations. At low frequencies, threshold shifts seldom reflected the losses of hair cells commonly found in the cochlear apex. Thus, the correlation of specific hair-cell losses and CAP threshold shifts at corresponding frequencies was poor. On the other hand, the total number of missing hair cells, irrespective of location, was a good, general indicator of the hearing capacity in a given ear. It appears that the factor or factors that makes cochleas susceptible to hair-cell loss with increasing age also affects other cochlear mechanisms that are necessary for normal functioning of the ear. PMID- 1917713 TI - Neonatal conductive hearing loss does not compromise brainstem auditory function and structure in rhesus monkeys. AB - The effect of conductive hearing loss on the maturation of the auditory pathway was evaluated using the auditory brainstem response (ABR) in rhesus monkeys. Ten newborn rhesus monkeys were assigned to control (N = 4), unilateral hearing loss (N = 3), or bilateral hearing loss (N = 3) groups. Hearing loss was created by surgically excising a 3 mm section of the external auditory canal and suturing the canal. Auditory brainstem responses to click stimuli were recorded prior to and after the surgical procedure and bi-monthly or monthly for a 14 month follow up period. Results showed that after surgery all ears developed an estimated 30 50 dB conductive hearing loss which was retained throughout the follow-up period. Contrary to expectations, the latencies of the ABR component waves decreased with age in all ears. When adjusted for hearing level, there were no differences between ears in maturation of the component waves of the ABR. These data suggest that, in primates, a conductive hearing loss does not affect the maturation of those aspects of the auditory pathway reflected in the ABR. Furthermore, the conductive losses were not accompanied by any discernible change in the neuronal sizes of brainstem auditory neurons or the volume of the cochlear nuclei. PMID- 1917714 TI - Effects of noise and salicylate on auditory evoked-response thresholds in the chinchilla. AB - The combined effects of noise and sodium salicylate on auditory sensitivity were examined in the chinchilla. Sensitivity was monitored by recording the evoked response recorded with an electrode implanted in the inferior colliculus. Sodium salicylate (300 mg/kg/day), an octave band of noise centered at 500 Hz (80 or 105 dB SPL), or both of these agents were delivered for 15 days. Threshold testing was performed at 7 frequencies before, during, and after exposure to the ototraumatic agent(s). The salicylate alone caused an average temporary threshold shift of less than 10 dB and essentially no permanent shift. Animals exposed to noise alone had temporary and permanent threshold shifts which were not significantly different from those observed in animals exposed to noise plus salicylate. The data suggest that a single daily injection of sodium salicylate, resulting in peak serum salicylate concentrations of 28 to 34 mg% 2 to 4 hours after delivery, does not exacerbate the temporary or permanent threshold shifts induced by 15-day, 24-hour-per day exposure to either a moderate- or high-level, low-frequency noise. A second series of experiments utilizing a higher dose of salicylate (450 mg/kg/day) was not completed due to a high mortality rate among subjects that received salicylate and were exposed to noise. This result was consistent with other recent examinations of the interaction of these agents. PMID- 1917715 TI - Unusual morphology of the stria vascularis in pigmented strain 2/NCR guinea pigs. AB - This paper reports an abnormality in the morphology of the apical stria vascularis of inbred 2/NCR guinea pigs as compared to outbred animals. Cochleas were embedded in plastic, sectioned, and examined in the light and electron microscopes. In the 2/NCR animals, the apical stria vascularis consisted of a cuboidal epithelium composed of a monolayer of poorly differentiated cells. Few or no capillaries were associated with this epithelium. No melanin pigment was present in the abnormal region of the stria in these animals, although pigmentation appeared normal in lower turns of the cochlea. Measurements of compound action potential thresholds between 2 and 40 kHz revealed no differences in auditory function between the two strains. PMID- 1917716 TI - Cochlear efferent neurones and protection against acoustic trauma: protection of outer hair cell receptor current and interanimal variability. AB - We have measured the changes in neural and microphonic sensitivity in the basal turn of the guinea-pig cochlea produced by intense acoustic overstimulation (10 kHz, 115 dB SPL for 60 s and 150 s). As reported previously, the drop in neural and microphonic sensitivities observed after overstimulation were highly correlated [Patuzzi et al. (1989) Hear. Res. 39, 189-202]. Presentation of a non traumatizing pure-tone to the contralateral ear (10 kHz, 80 dB SPL) during acoustic overstimulation reduced the amount of acoustic trauma measured using the neural response or the microphonic response. Transection of the medial olivo cochlear system of efferent fibres at the floor of the fourth ventricle abolished this protective effect of contralateral sound and dramatically reduced the variability in the data. Since the low-frequency microphonic is a simple measure of the receptor current through the outer hair cells, and this current probably plays a part in enhancing the mechanical sensitivity of the cochlea, the protection of the microphonic we have observed suggests that the efferent system protects neural sensitivity by protecting the mechano-electrical transduction of outer hair cells. The drop in variability after sectioning the efferents also suggests that inter-animal variations in susceptibility to noise trauma may be a consequence of differing tonic activity of the efferents, and/or a variation in the sensitivity of the efferent pathway. PMID- 1917717 TI - Pilocarpine elicits the interdental cell secretory activity of the inner ear. AB - Subcutaneous injection of pilocarpine in guinea pigs resulted in the following ultrastructural changes: 1) the apical cavities of the interdental cells were filled with a substance indistinguishable from the overlying amorphous layer of the TM; 2) a great number of spherical structures appeared over the limbal portion of the tectorial membrane. In TEM photomicrographs these structures displayed the same appearance as the amorphous layer of the TM and were usually continuous to it; 3) the number of holes that decorate the upper surface of the limbal portion of the TM was dramatically increased and it was found that they connect the endolymphatic space to the apical cavities of the interdental cells; 4) there was an increase in the number of the small extracellular vesicles found in the clear spaces of the tectorial membrane. These facts suggest that pilocarpine stimulates the secretion of the interdental cells, confirming the existence of the secretory processes previously described (Prieto et al., 1990). These findings can be related to the turnover of the TM in the adult animal and, perhaps, to the secretion of some organic compound to the endolymph. We postulate that the actions of pilocarpine on the interdental cells are most probably mediated by the activation of muscarinic acetylcholine receptors in these cells. PMID- 1917718 TI - Brainstem auditory evoked responses from birth to adulthood: normative data of latency and interval. AB - Development of wave latency and interpeak interval (IPI) in brainstem auditory evoked responses (BAER) from birth to adulthood was examined. Adult equivalence was reached for most wave latencies and IPIs between the ages of 9 months and 3 years. The observation of the III-V/I-III interval ratio suggests that after term data the I-III IPI decreases more than the III-V IPI. I-III, III-V and I-V IPIs shortened from the l-month old group to the 4-6 year old group by 22%, 15% and 19% respectively. The III-V/I-III interval ration may be a useful BAER measure. Normative data of various BAER measures at different ages are presented. The slope of the L-I function for wave V was slightly steeper in younger groups than in older groups (40 microseconds/dB in the 1-month old group 32 microseconds/dB in the adult group). This change which was accompanied by an age-related difference in the absolute wave latency. It is suggested that age-dependent norms should be used in evaluation of the L-I function. PMID- 1917719 TI - Auditory nerve of the normal and jaundiced rat. I. Spontaneous discharge rate and cochlear nerve histology. AB - Hyperbilirubinemia is a major problem in neonatal intensive care. Hearing impairment is one of its sequelae. Although lesions of the central auditory pathways are known to be associated with this disorder in both humans and homozygous Gunn rats, the presence of cochler pathology is still controversial. The purpose of this study was to examine the functional integrity of the peripheral auditory system in the Gunn rat. The Gunn rat is a mutant of the Wistar strain with congenital deficiency of the liver enzyme uridine diphosphoglucuronyl transferase which is essential for bilirubin conjugation. This deficiency is inherited as an autosomal recessive trait, with the homozygous animals (jj) showing evidence of bilirubin encephalopathy. The heterozygotes (Jj) have 50% enzyme deficiency and are not jaundiced. The Long-Evans rat served as a control. The approach was to study the discharge characteristics fo single auditory nerve fibers using standard procedures in a closed and calibrated sound system. Various response measurements which would reveal pathological processes in the cochlea were analyzed. In this study, spontaneous discharge rate distribution and interspike interval statistics derived from Gunn rat auditory nerve recordings were found to be within the normal range, and cochlear nerve histology showed no evidence of neuropathy. PMID- 1917720 TI - Auditory nerve of the normal and jaundiced rat. II. Frequency selectivity and two tone rate suppression. AB - This study is the continuation of the functional probing of the auditory periphery in the normal and jaundiced rat. Threshold tuning curves from normal rat auditory nerve fibers were comparable to those reported in other mammals. Life-long unconjugated hyperbilirubinemia does not appear to have a widespread, demonstrable effect on cochlear frequency selectivity and sensitivity as measured by the shapes of FTCs of single auditory nerve fibers. Most fibers from the jj Gunn rats had threshold tuning curves as sharp as those from control animals (Jj Gunn and Long-Evans). Any difference seems to lie in a greater threshold variability, particularly for the high-SR fibers, for the Gunn rat strain. Two tone rate suppression, particularly above CF, was detected in most fibers from the three groups of rats. The optimal suppression frequency (SF) as a function of CF displayed the same progression. Suppression thresholds at any given CF were generally higher for high-SR fibers than for low-SR fibers for all three groups of animals. PMID- 1917721 TI - Leadership: an essential facet of a successful practice. PMID- 1917722 TI - Bacteria in food packaging paper and board. AB - The bacteria of food packaging paper and board were studied. Most of the aerobic strains were spore-formers; members of the genus Bacillus with B. cereus group (B. cereus, B. mycoides, B. thuringiensis), B. polymyxa group (B. polymyxa, B. circulans, B. macerans, B. pabuli), B. brevis and B. licheniformis predominated. The main source of spore-forming bacteria in paper and board was the broke (rejected paper or board, which is repulped and recycled into the process). Gram negative bacteria were rare in paper and board in spite of their abundance in the stock. A strain of B. pumilus forming clumping, hairy spores may be of significance in aseptic packaging. PMID- 1917723 TI - Effect of chemical treatments on the micro-organisms associated with malting of sorghum grains and sorghum malt. AB - The effect of five chemical preservatives on the micro-organisms associated with sorghum grain and malts was investigated. Sorbic acid, sodium benzoate, nisin, formaldehyde and lime at concentrations up to 500, 100, 1000, 1500 and 2000 ppm, respectively did not adversely affect the malting properties of sorghum grain. Only HCHO and Ca(OH)2, each of which prevented bacteria and mould growth at 500 and 2000 ppm, respectively, were sufficiently effective at maximum practicable concentrations to control microbial contamination during malting. PMID- 1917724 TI - The characteristics of a new non-spore-forming cellulolytic mesophilic anaerobe strain CM126 isolated from municipal sewage sludge. AB - A new mesophilic anaerobic cellulolytic bacterium, CM126, was isolated from an anaerobic sewage sludge digester. The organism was non-spore-forming, rod-shaped, Gram-negative and motile with peritrichous flagella. It fermented microcrystalline Avicel cellulose, xylan, Solka floc cellulose, filter paper, L arabinose, D-xylose, beta-methyl xyloside, D-glucose, cellobiose and xylitol and produced indole. The % G + C content was 36. Acetic acid, ethanol, lactic acid, pyruvic acid, carbon dioxide and hydrogen were produced as metabolic products. This strain could grow at 20-44.5 degrees C and at pH values 5.2-7.4 with optimal growth at 37-41.5 degrees C and pH 7. Both endoglucanase and xylanase were detected in the supernatant fluid of a culture grown on medium containing Avicel cellulose and cellobiose. Exoglucanase could not be found in either supernatant fluid or the cell lysate. When cellulose and cellobiose fermentation were compared, the enzyme production rate in cellobiose fermentation was higher than in cellulose fermentation. The optimum pH for both enzyme activities was 5.0, the optimum temperature was 40 degrees C for the endoglucanase and 50 degrees C for the xylanase. Both enzyme activities were inhibited at 70 degrees C Co-culture of this organism with a Methanosarcina sp. (A145) had no effect on cellulose degradation and both endoglucanase and xylanase were stable in the co-culture. PMID- 1917725 TI - Deoxyribonuclease activities in Myxococcus coralloides D. AB - Myxococcus coralloides D produced cell-bound deoxyribonucleases (DNases) during the exponential phase of growth in liquid medium. DNase activity was much higher than that detected in other myxobacterial strains and was fractionated into three different peaks by filtration through Sephadex G-200. The DNases were named G, M and P. The optimum temperatures were 37 degrees C, 33 degrees C and 25 degrees C respectively, although high activities were recorded over the temperature range 20-45 degrees C. The pH range of high activity was between 6.0 and 9.0, with an optimum for each DNase at 8.0. DNases M and P were strongly inhibited by low concentrations of NaCl, but activity of DNase G was less affected by NaCl. The three activities required divalent metal ions as cofactors (especially Mg2+ and Mn2+); however, other metal ions (Fe2+, Ni2+, Zn2+) were inhibitors. The molecular weights were estimated by gel filtration chromatography and SDS-PAGE as 44 kDa (DNase G), 49 kDa (DNase M) and 39 kDa (DNase P). PMID- 1917727 TI - Distribution of Aeromonas species in waters with different levels of pollution. AB - Strains of Aeromonas spp. (883) were isolated from 10 stations in the north-west of Spain. Biotyping of the strains gave: 55% Aeromonas caviae, 34% A. hydrophila, 6% A. sobria and 5% Aeromonas spp. Phenotypic characters that have been claimed to be related to virulence such as haemolysis and the Voges-Proskauer reaction were detected mostly in A. hydrophila and A. sobria. The distribution of the species was significantly related to levels of faecal pollution in waters. Aeromonas caviae predominated in sewage and waters with a high degree of faecal pollution. In less polluted waters, either fresh or marine, A. caviae and A. hydrophila were almost equally distributed. In waters with low or no faecal pollution, the proportion of A. sobria to other species increased considerably. PMID- 1917728 TI - Yeasts associated with red meats. PMID- 1917726 TI - Relation of human serum antibody against Staphylococcus epidermidis cell surface polysaccharide detected by enzyme-linked immunosorbent assay to passive protection in the mouse. AB - A specific and rapid enzyme-linked immunosorbent assay (ELISA) has been applied for the detection of immunoglobulins to Staphylococcus epidermidis cell surface polysaccharides in human serum. Positive IgG, IgM and IgA titres of more than 1: 6400, 1: 1600 and 1: 400 were observed with this assay against passive protective human serum. However, IgG, IgM and IgA titres of less than 1: 400, 1: 100 and 1: 50 were shown in non-protective serum. When the cross-reactivity of passive protective human serum to homologous and heterologous cell surface polysaccharides was examined by inhibition test with ELISA, remarkable inhibition was shown with homologous cell surface polysaccharide, whereas no inhibition was observed with heterologous substances. According to these results, the quantitation of human serum antibody by the ELISA method against Staph. epidermidis cell surface polysaccharide was found to be significant for the demonstration of passive protective activities against Staph. epidermidis. PMID- 1917729 TI - Fractal perspectives in pulmonary physiology. AB - Like other organs that exchange substantial quantities of material with blood, the lung accommodates a large two-dimensional surface in a component three dimensional volume. The lung's structure shows a resemblance to certain one- and two-dimensional mathematical functions that possess plane- and space-filling properties. When viewed from a conventional geometric perspective, many of the familiar forms and functions of pulmonary tissue appear to possess unusual qualities that defy explanation. Mathematically, they behave as though they had a fractional geometric dimension. This property is shared by a class of functions known as fractals. Fractals are described, and practical techniques are presented to measure the properties of the edges and surfaces of the lung. The consequences of fractal structure are also considered for the bronchial tree, pulmonary vasculature, and microcirculation. Insights arising from viewing the lung in this new perspective are summarized. PMID- 1917730 TI - Effects of systole-specific pericardial pressure increases on coronary flow. AB - It has been postulated that intrathoracic pressure increases may impair cardiac function by decreasing coronary flow. To determine whether altered coronary flow causes or results from change in cardiac function, we used 14 anesthetized dogs in propranolol-induced heart failure following atrioventricular node ablation. After thoracoabdominal binding, the animals were paced and ventilated at the same frequency, and inspiration was synchronized with cardiac systole, resulting in systole-specific pericardial pressure increases (SSPPI). At SSPPI magnitudes of 15 and 30 mmHg, left atrial transmural pressure decreased and cardiac output increased, whereas decreases in left ventricular end-systolic transmural pressure and myocardial O2 consumption were directly related. Concurrent decreases in coronary sinus flow (CSF) and coronary arteriovenous O2 gradient with SSPPI 15 mmHg indicate autoregulation. However, the arteriovenous O2 gradient remained unaltered with SSPPI 30 mmHg, despite further decrease in CSF. Because the absolute diastolic aortic pressure decreased, a limit may exist for increasing SSPPI above which CSF may be directly affected. PMID- 1917731 TI - Water homeostasis in desert-dwelling horses. AB - This study set out to investigate tolerance of the body water pool to short-term water deprivation in horses and, in particular, to assess whether feral horses from the Namib Desert showed tolerance to dehydration superior to Transvaal. Hydration status was compared in six feral horses from the Namib Desert and in six Boerperd farm horses under conditions of normal hydration and after 72 h of dehydration. Under normal hydration, the two groups did not differ significantly in water intake, plasma sodium and potassium concentrations, plasma osmolality, hematocrit, total plasma protein, body water content, or water turnover (ml.kg 0.82.day-1). The Namib horses were significantly smaller (P less than 0.0001) and turned over 5 liters less water per day than the Boerperd during normal hydration and 4 liters less during dehydration. Increases in plasma sodium concentration after 72 h of dehydration were greater (P less than 0.05) in the Namib horses. It was concluded that horses can easily tolerate water deprivation that results in a 12% reductions in body mass. The feral horses of the Namib desert were not significantly different per unit mass from domestic horses with regard to indexes of total body water content under conditions of normal hydration and after 72 h of dehydration. Their smaller size and, hence, lower water turnover might be mechanisms they use for survival in the Namib Desert. PMID- 1917732 TI - Relationship between alae nasi activation and breathing route during exercise in humans. AB - We studied the relationship between alae nasi muscle (AN) activation and breathing route in normal subjects during exercise. Nasal and oral airflow were measured simultaneously using a partitioned face mask and were recorded with the AN electromyogram. Subjects breathed via 1) the nose and mouth (NM) 2) the nose only (N), or 3) the mouth only (M). As ventilation (VE) rose progressively, the peak phasic inspiratory AN activity (IAAN) increased for all breathing routes. IAAN during N [11.8 +/- 2.0 arbitrary units (AU)] was greater than during NM (3.3 +/- 1.3 AU) and M (2.4 +/- 1.0 AU; P less than 0.01) measured at the highest common VE (over a 10-l/min range). At the highest 20% of IAAN recorded during NM, the total VE during N (24 +/- 5 l/min). However, for the same IAAN, nasal VE during NM (27 +/- 3 l/min) was similar to that during N. Thus, as ventilation increases during exercise, AN activity and nasal ventilation are tightly correlated, independently of flow through the mouth. This suggests either reflex modulation of AN activity by nasal flow or coordination of AN activation with the flow-partitioning mechanism of the upper airway. PMID- 1917733 TI - Cold exposure during military operations: effects on anaerobic performance. AB - This study examined the effects of military field operations (MFO) under different environmental conditions on anaerobic performance. US Marines were tested in the field under the following conditions: 1) noncold environment (NC; n = 30, 10-32 degrees C) and 2) cold environment (CO; n = 32, -2 to -22 degrees C). Subjects performed 30-s Wingate tests (WIN) pre- and immediately post-MFO to assess anaerobic performance. The MFO consisted of approximately 4.5 days of combat training maneuvers while carrying field equipment (packs and weapon, approximately 25 kg). WIN measures obtained were absolute and relative mean power (MP), 5-s peak power (PP), and fatigue index (% decline). Significant main effects (P less than 0.01) were observed for time (pre-post MFO). Reductions occurred in absolute MP [651.8 +/- 30.3 to 616.4 +/- 28.5 (SE) W] and PP (897.8 +/- 41.6 to 857.0 +/- 39.1 W); however, no effect on fatigue index was seen. Significant interaction effects (P less than 0.05) were observed in relative measures. Reductions (pre-post) in MP (NC = 8.64 +/- 0.16 to 8.37 +/- 0.14 W/kg; CO = 8.91 +/- 0.26 to 8.04 +/- 0.15 W/kg) and PP (NC = 11.80 +/- 0.24 to 11.61 +/ 0.33 W/kg; CO = 12.23 +/- 0.35 to 11.20 +/- 0.19 W/kg) were greater under CO than NC conditions. These changes were found despite significant (P less than 0.05) but comparable pre-post weight reductions in both CO and NC conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917734 TI - Differences between VO2 maxima of twitch and tetanic contractions are related to blood flow. AB - The purpose of this investigation was to compare oxygen uptake (VO2) and fatigue characteristics of isotonic tetanic contractions with those observed during isotonic twitches in dog gastrocnemius-plantaris muscle. Tetanic contractions (1/s, 200-ms trains of 50 impulses/s) elicited a peak VO2 of 9.01 +/- 0.42 mumol.g-1.min-1, which declined 29% in 30 min. The peak was significantly lower during 4/s twitches (6.23 +/- 0.36 mumol.g-1.min-1), but the rate of decline was similar. Peak blood flow (Q) was 37% higher and decreased more slowly during tetanic than twitch contractions. VO2/Q and VO2/venous PO2 were similar in both groups at peak VO2 and later declined or remained constant over time. Power was significantly greater with tetanic contractions with the relative decline between 3 and 30 min similar in both groups (32 and 37%). In conclusion, tetanic contractions result in significantly higher VO2 and power than do twitch contractions. This was derived primarily from increased Q because the arteriovenous O2 difference was similar. A significant determinant of the difference in Q between twitch and tetanic contractions is mechanical hindrance of Q. There is relatively more time for unhindered flow in the tetanic contractions. In electrically stimulated muscles, maximal VO2 is related to Q and reflects mainly Q through the muscle rather than the VO2 capacity of the muscle. PMID- 1917735 TI - Enhanced exercise-induced rise of aldosterone and vasopressin preceding mountain sickness. AB - A possible contribution of exercise to the fluid retention associated with acute mountain sickness (AMS) was investigated in 17 mountaineers who underwent an exercise test for 30 min on a bicycle ergometer with a constant work load of 148 +/- 9 (SE) W at low altitude (LA) and with 103 +/- 6 W 4-7 h after arrival at 4,559 m or high altitude (HA). Mean heart rates during exercise at both altitudes and during active ascent to HA were similar. Exercise-induced changes at LA did not differ significantly between the eight subjects who stayed well and the nine subjects who developed AMS during a 3-day sojourn at 4,559 m. At HA, O2 saturation before (71 +/- 2 vs. 83 +/- 2%, P less than 0.01) and during exercise (67 +/- 2 vs. 72 +/- 1%, P less than 0.025) was lower and exercise-induced increase of plasma aldosterone (617 +/- 116 vs. 233 +/- 42 pmol/l, P less than 0.025) and plasma antidiuretic hormone (23.8 +/- 14.4 vs. 3.4 +/- 1.8 pmol/l, P less than 0.05) was greater in the AMS group, whereas exercise-induced rise of plasma atrial natriuretic factor and changes of hematocrit, potassium, and osmolality in plasma were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917737 TI - Diaphragmatic intramuscular pressure in relation to tension, shortening, and blood flow. AB - We used an in situ isolated diaphragmatic preparation in anesthetized dogs to relate intramuscular pressure (IMP) to the blood flow, tension, and shortening of the diaphragm. In this preparation, the diaphragm shortens in a fashion similar to the intact diaphragm. Tension was measured by transducers attached to the left costal margin, which was detached from the rib cage and abdomen; IMP was measured by a miniature transducer placed between muscle fibers; length was measured by sonomicrometry; and diaphragmatic blood flow was monitored by measuring left phrenic arterial flow. In protocol 1, the relationships between tension, shortening, and IMP were assessed by stimulating the diaphragm for 2 s at various frequencies. Tension and shortening increased with increasing stimulation frequency up to 50 Hz with no change thereafter. Tension was linearly related to IMP. Similarly, there was a linear relationship between the degree of shortening and IMP; however, the slopes varied considerably between dogs. In protocol 2, the diaphragm was paced intermittently (12 trains/min, duty cycle of 0.5) with a gradual increase in stimulation frequency. Blood flow during contraction phase rose slightly at low tension and then declined significantly when tension exceeded 30% of maximum, whereas relaxation-phase flow increased with the increase in tension. IMP rose linearly with the increase in tension, and the IMP, at the point where contraction-phase flow became severely limited, was 50 +/- 14 mmHg (mean +/- SE). We conclude the following. 1) IMP is linearly related to tension and shortening; however, because tension and shortening changed simultaneously during contractions, the independent relationship of either tension or shortening and IMP remained untested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917736 TI - Physiological responses to glycerol ingestion during exercise. AB - To study selected cardiovascular, thermoregulatory, and hormonal responses to the consumption of glycerol solutions during exercise, nine subjects cycled for 90 min at 50% peak O2 uptake in a 30 degree C, 45% relative humidity environment. Beverages tested included a 10% glycerol solution (G), a 6% carbohydrate electrolyte beverage (CE), the 6% carbohydrate-electrolyte beverage plus 4% glycerol (CEG), and a water placebo (WP) ingested at regular intervals during the first 60 min of exercise. The beverages were administered in counterbalanced order with subjects serving as their own controls. Ingestion of the glycerol solutions resulted in an increase in plasma osmolality and attenuation of the decrease in plasma volume associated with the WP treatment (P less than 0.05). Plasma renin activity was highest with WP (P less than 0.05), and G was associated with increased antidiuretic hormone levels (P less than 0.05). Ratings of perceived thirst were lowest for CEG and G, and the frequency of gastrointestinal distress was greatest for G (P less than 0.05). However, no differences among beverage treatments were observed for heart rate, esophageal temperature, sweat rate, ratings of perceived exertion, or changes in cortisol and aldosterone levels. These data indicate that there are no substantial metabolic, hormonal, cardiovascular, or thermoregulatory advantages to the consumption of solutions containing 4 or 10% glycerol during exercise. PMID- 1917738 TI - Doubly labeled water measurement of human energy expenditure during strenuous exercise. AB - The energy expenditures (EE) of 23 adult male Marines were measured during a strenuous 11-day cold-weather field exercise at 2,200- to 2,550-m elevation by both doubly labeled water (2H2 18O, DLW) and intake balance methods. The DLW EE calculations were corrected for changes in baseline isotopic abundances in a control group that did not receive 2H2 18O. Intake balance EE was estimated from the change in body energy stores and food intake. Body energy-store changes were calculated from anthropometric [-1,574 +/- 144 (SE) kcal/day] and isotope dilution (-1,872 +/- 293 kcal/day) measurements made before and after the field exercise. The subjects kept daily logbook records of ration consumption (3,132 +/ 165 kcal/day). Mean DLW EE (4,919 +/- 190 kcal/day) did not differ significantly from intake balance EE estimated from food intake and either anthropometric (4,705 +/- 181 kcal/day) or isotope dilution (5,004 +/- 240 kcal/day) estimates of the change in body energy stores. The DLW method can be used with at least the same degree of confidence as the intake balance method to measure the EE of active free-living humans. PMID- 1917739 TI - Ventilatory response of the sleeping newborn to CO2 during normoxic rebreathing. AB - The ventilatory response of the newborn to CO2 was studied using a rebreathing method that minimized changes in arterial PO2 during the test. The aim was to study the variability of the ventilatory response to CO2 and take this into account to assess the relative magnitude of the response to CO2 during rapid-eye movement (REM) sleep and quiet sleep (QS). Five full-term babies aged 4-6 days were given 5% CO2 in air to rebreathe for 1.5-3 min. O2 was added to the rebreathing circuit to maintain arterial O2 saturation and transcutaneous PO2 (Ptco2) at prerebreathing levels. Tests were repeated four to five times in REM sleep and QS. Mean Ptco2 levels varied between individuals but were similar during REM sleep and QS tests for each subject. The mean coefficient of variability of the ventilatory response was 35% (range 15-77%) during QS and 120% (range 32-220%) during REM sleep. PtcO2 fluctuations during tests [6.0 +/- 3.0 (SD) Torr, range 1-13 Torr] were not correlated with ventilatory response. Overall the ventilatory response was significantly lower in REM sleep than in QS (12.2 +/- 3.0 vs. 38.7 +/- 3.0 ml.min-1.Torr-1.kg-1, P less than 0.001; 2-way analysis of variance) due to a small (nonsignificant) fall in the tidal volume response and a significant fall in breathing rate. In 12 REM sleep tests there was no significant ventilatory response; mean inspiratory flow increased significantly during 8 of these 12 tests. We conclude that there is a significant decrease in the ventilatory response of the newborn to CO2 rebreathing during REM sleep compared with QS. PMID- 1917741 TI - Glyconeogenic and glycogenic enzymes in chronically active and normal skeletal muscle. AB - The chronically active (pseudomyotonic) gastrocnemius muscle in the C57B16J dy2J/dy2J mouse contains both elevated lactate and glycogen as well as fibers that have high amounts of glycogen and enhanced glyconeogenic activity. In the present study we analyze the activities of some key glyconeogenic enzymes to assess the causes of elevated muscle glycogen and to determine the pathway for glycogen synthesis from lactate. Glycogen synthase, malate dehydrogenase, phosphoenolpyruvate carboxykinase, and malic enzyme were all elevated in homogenates of the chronically active muscle. Activities of glycogen phosphorylase and fructose 1,6-bisphosphatase were decreased in whole muscle homogenates. Histochemistry demonstrated that the high-glycogen fibers were typically fast-twitch glycolytic fibers that had high glycogen synthase, glycogen phosphorylase, and malic enzyme activities. Malate dehydrogenase activity followed succinate dehydrogenase activity and did not correlate to high-glycogen fibers. Thus the high-glycogen fibers have an elevated enzymatic capacity for glycogen synthesis from lactate, and the pathway may involve use of the pyruvate kinase bypass enzymes. PMID- 1917740 TI - Effect of chest wall vibration on breathlessness in normal subjects. AB - This study evaluated the effect of chest wall vibration (115 Hz) on breathlessness. Breathlessness was induced in normal subjects by a combination of hypercapnia and an inspiratory resistive load; both minute ventilation and end tidal CO2 were kept constant. Cross-modality matching was used to rate breathlessness. Ratings during intercostal vibration were expressed as a percentage of ratings during the control condition (either deltoid vibration or no vibration). To evaluate their potential contribution to any changes in breathlessness, we assessed several aspects of ventilation, including chest wall configuration, functional residual capacity (FRC), and the ventilatory response to steady-state hypercapnia. Intercostal vibration reduced breathlessness ratings by 6.5 +/- 5.7% compared with deltoid vibration (P less than 0.05) and by 7.0 +/- 8.3% compared with no vibration (P less than 0.05). The reduction in breathlessness was accompanied by either no change or negligible change in minute ventilation, tidal volume, frequency, duty cycle, compartmental ventilation, FRC, and the steady-state hypercapnic response. We conclude that chest wall vibration reduces breathlessness and speculate that it may do so through stimulation of receptors in the chest wall. PMID- 1917743 TI - Additive effects of training and high-fat diet on energy metabolism during exercise. AB - This study was conducted to obtain additional information about the adaptations after 12 wk of high-fat diet (HFD) per se or HFD combined with endurance training in the rat using a two [diet: carbohydrate (CHO) or HFD] by two (training: sedentary or trained) by two (condition at death: rested or exercised) factorial design. Adaptation to prolonged HFD increases maximal O2 uptake (VO2max; 13%, P less than 0.05) and submaximal running endurance (+64%, P less than 0.05). This enhancement in exercise capacity could be attributed to 1) an increase in skeletal muscle aerobic enzyme activities (3-hydroxyacyl-CoA dehydrogenase and citrate synthase in soleus and red quadriceps) or 2) a decrease in liver glycogen breakdown in response to 1 h exercise at 80% VO2max. When training is superimposed to HFD, the most prominent finding provided by this study is that the diet-induced effects are cumulative with the well-known training effect on VO2max, exercise endurance, oxidative capacity of red muscle, and metabolic responses to exercise, with a further reduction in liver glycogen breakdown. PMID- 1917742 TI - Mechanism for pressor response to nonexertional heating in the conscious rat. AB - The purpose of this study was to determine the systemic hemodynamic mechanism(s) underlying the pressor response to nonexertional heat stress in the unrestrained conscious rat. After a 60-min control period [ambient temperature (Ta) 24 degrees C], male Sprague-Dawley rats (260-340 g) were exposed to a Ta of 42 degrees C until a colonic temperature (Tc) of 41 degrees C was attained. As Tc rose from control levels (38.1 +/- 0.1 degrees C) to 41 degrees C, mean arterial blood pressure (carotid artery catheter, n = 33) increased from 124 +/- 2 to 151 +/- 2 mmHg (P less than 0.05). During this period, heart rate increased (395 +/- 5 to 430 +/- 6 beats/min, P less than 0.05) and stroke volume remained unchanged. As a result, ascending aorta blood flow velocity (Doppler flow probe, n = 8), used as an index of cardiac output, did not change from control levels during heating, but there was a progressive Tc-dependent increase in systemic vascular resistance (+30% at end heating, P less than 0.05). This systemic vasoconstrictor response was associated with decreases in blood flow (-31 +/- 9 and -21 +/- 5%) and increases in vascular resistance (94 +/- 16 and 53 +/- 8%; all P less than 0.05) in the superior mesenteric and renal arteries (n = 8 each) and increases in plasma norepinephrine (303 +/- 37 to 1,237 +/- 262 pg/ml) and epinephrine (148 +/ 28 to 708 +/- 145 pg/ml) concentrations (n = 12, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917744 TI - Skeletal muscle relaxation rate after fasting or hypocaloric feeding. AB - The effect of malnutrition on skeletal muscle relaxation is not entirely clear; some studies indicate no change and others a slowing of the relaxation rate. We investigated whether these different results were due to type of malnutrition, muscle fiber type composition, or the index used to express relaxation rate. The effect of a 2-day fast (16% body wt loss) or 1 wk of hypocaloric feeding (22.6% wt loss) on relaxation rates of soleus and extensor digitorum longus (EDL) muscles was studied in situ with the use of anesthetized adult Wistar rats. Relaxation rates were assessed for twitch contractions using half-relaxation times and exponential phase half-times and for tetanic contractions using exponential phase half-times. The rate of relaxation was unaffected by fasting, whereas hypocaloric feeding reduced relaxation rates after twitch and tetanic contractions in both soleus and EDL muscles. We conclude that slowing of skeletal muscle relaxation rate occurs after 1 wk of hypocaloric feeding but not after 2 days of fasting. The slowing is independent of muscle fiber composition, type of contraction, or the index used to express relaxation rate. PMID- 1917745 TI - Modulation of vascular reactivity to serotonin in the dog lung. AB - Experiments were conducted to compare the effects of cyclooxygenase inhibition (COI) on vascular reactivity to serotonin (5-HT) in the isolated blood-perfused canine left lower lung lobe (LLL) and in isolated canine intrapulmonary lobar artery rings with and without a functional endothelium. LLLs (n = 6), perfused at constant blood flow, were challenged with bolus doses of 50, 100, and 250 micrograms 5-HT before COI, after COI with 45 microM meclofenamate, and after infusion of prostacyclin (PGI2) during COI. Lobar vascular resistance was segmentally partitioned by venous occlusion. Pulmonary arterial pressure increased from 13.5 +/- 1.0 to 16.3 +/- 0.8 cmH2O (P less than 0.01) after COI but declined to 13.1 +/- 1.1 cmH2O (P less than 0.01) subsequent to PGI2 infusion (91.3 +/- 14.5 ng.min-1.g LLL-1). The pulmonary arterial pressure changes were related to changes in postcapillary resistance. The dose-dependent pressor response to 5-HT was potentiated by COI (P less than 0.01) but reversibly attenuated (P less than 0.05) by PGI2 infusion. Isolated intrapulmonary artery rings (2-4 mm diam) exhibited a dose-related increase in contractile tension to 5 HT. The response to 5-HT was enhanced (P less than 0.05) in rings devoid of a functional endothelium. However, COI (10 microM indomethacin) did not alter (P greater than 0.05) the dose-related increase in contractile tension to 5-HT in rings with an intact endothelium. Our results suggest that both PGI2 and endothelium-derived relaxing factors modulate pulmonary vascular reactivity to 5 HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917747 TI - Sweating and skin blood flow during exercise: effects of age and maximal oxygen uptake. AB - Individuals greater than or equal to 60 yr of age are more susceptible to hyperthermia than younger people. However, the mechanisms involved remain unclear. To gain further insight, we examined the heat loss responses of 7 young (24-30 yr) and 13 older (58-74 yr) men during 20 min of cycle exercise [67.5% maximal O2 uptake (VO2max)] in a warm environment (30 degrees C, 55% relative humidity). Forearm blood flow (FBF) and chest sweat rate (SR) were plotted as a function of the weighted average of mean skin and esophageal temperatures [Tes(w)] during exercise. The sensitivity and threshold for each response were defined as the slope and Tes(w) at the onset of the response, respectively. When the young sedentary men were compared with a subgroup (n = 7) of the older physically active men with similar VO2max, the SR and FBF responses of the two groups did not differ significantly. However, when the young men were compared with a subgroup of older sedentary men with a similar maximal O2 pulse, the SR and FBF sensitivities were significantly reduced by 62 and 40%, respectively. These findings suggest that during a short exercise bout either 1) there is no primary effect of aging on heat loss responses but, rather, changes are associated with the age-related decrease in VO2max or 2) the decline in heat loss responses due to aging may be masked by repeated exercise training. PMID- 1917746 TI - Independent control of mucosal and total airway blood flow during hypoxemia. AB - In the larger airways, the blood circulation forms a subepithelial (mucosal) and outer (peribronchial) microvascular network. This raises the possibility that blood flow in these two networks is regulated independently. We used hypoxemia as a stimulus to induce changes in tracheal mucosal blood flow normalized for systemic arterial pressure (Qtr n) measured with an inert soluble gas technique and total bronchial blood flow (Qbr) and normalized Qbr (Qbrn) measured with an electromagnetic flow probe in anesthetized sheep. Fifteen minutes of hypoxemia [PO2 40 +/- 7 (SD) Torr] decreased mean Qtr n from 1.1 +/- 0.4 to 0.8 +/- 0.4 ml.min-1.mmHg-1.10(2) (-27%; P less than 0.05; n = 7) and increased mean Qbr n from 12.1 +/- 3.2 to 17.1 +/- 5.4 ml.min-1.mmHg-1.10(2) (+41%; P less than 0.05; n = 6). The rise in Qbr correlated with cardiac output (r = 0.68; P less than 0.05). Phentolamine pretreatment (0.1 mg/kg iv) blunted the hypoxemia-related decrease of mean Qtr n (-8%; P = NS). Tyramine (2.5 mg) applied locally to the trachea decreased mean Qtr n significantly after 30 and 45 min by 31 and 19%, respectively (P less than 0.05). 6-Hydroxydopamine (0.2 mg 4 times for 1 h locally applied) prevented the hypoxemia-induced as well as local tyramine induced decrease in mean Qtr n (0 and 0%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917748 TI - Pulmonary blood flow and ventilation-perfusion heterogeneity. AB - We studied the independent influence of changes in perfusion on pulmonary gas exchange in the left lower lobe (LLL) of anesthetized dogs. Blood flow to the LLL (QLLL) was raised 50% (increased QLLL) or reduced 50% (decreased QLLL) from baseline by partial occlusion of the right or left pulmonary artery, respectively. Minute ventilation and alveolar PCO2 of the LLL remained constant throughout the study. We determined ventilation-perfusion distributions of the LLL using the multiple inert gas elimination technique. Increased QLLL impaired LLL pulmonary gas exchange. All dispersion indexes and all arterial-alveolar difference areas increased (P less than 0.01). Decreased QLLL increased the log standard deviation of the perfusion distribution (P less than 0.05) and reduced the log standard deviation of the ventilation distribution (P less than 0.01) but did not affect the dispersion indexes or alveolar-arterial difference areas. We conclude that ventilation-perfusion heterogeneity is increased by independent changes in perfusion from normal baseline blood flow, even when ventilation and alveolar gas composition remain constant. PMID- 1917749 TI - Frequency characteristics of airway and tissue impedances in respiratory diseases. AB - We measured the frequency characteristics (at 10-40 Hz) of airway (Za) and tissue (Zt) impedances in cases of chronic obstructive pulmonary disease [asthmatic bronchitis (AB), chronic pulmonary emphysema (CPE)] and interstitial pneumonitis (IP) by use of an improved random noise oscillation and body box method. The results were then compared with those obtained for normal subjects. The real part of Za was markedly elevated in patients with AB but only slightly elevated in those with CPE. To interpret these data we used an electromechanical analogue including serial inhomogeneity with shunt impedance. From this model we concluded that AB causes both the central and peripheral airway resistances to increase, while CPE brings about a rise mainly in peripheral resistance. In IP patients, only the imaginary part of Zt decreased, which might reflect the decrease in both lung and chest wall compliance. In CPE patients, but not in AB patients, the real part of Zt fell. These data were consistent with the assumption that the decrease in mass per unit volume of lung tissue and hyperinflation of the chest wall in CPE patients might lower the tissue resistances. PMID- 1917750 TI - Effect of waveforms of inspired gas tension on the respiratory oscillations of carotid body discharge. AB - The responses of carotid body chemoreceptor discharge to repeated ramps (20- to 60-s forcing cycle durations) of inspired gas tensions were studied in spontaneously breathing and in artificially ventilated pentobarbitone anesthetized cats. In all animals the mean intensity of chemoreceptor discharge followed the frequency of the forcing cycle, and superimposed on this were oscillations at the frequency of ventilation (breath-by-breath oscillations). The amplitude of the breath-by-breath oscillations in discharge was often large, and it waxed and waned with the forcing cycle. It was greatest when the mean level of discharge was falling and smallest near the peak of mean discharge. No qualitative differences were observed between PO2-alone forcing in constant normocapnia and PCO2-alone forcing in constant hypoxia. The variation in the amplitudes of breath-by-breath oscillations was shown to be due primarily to variations in the amplitudes of the downslope component of the discharge oscillation. Variations in the upslope component of individual oscillations were small. The factors responsible for the breath-by-breath oscillations are discussed, and it is concluded that the shape of the waveform of arterial gas tensions that stimulate the peripheral chemoreceptors departs markedly from that of a line joining end-tidal gas tensions. This causes breath-by-breath oscillations of discharge to be very large after an "off" stimulus. Reflex studies involving the forcing of respiratory gases should therefore include consideration of these effects. PMID- 1917751 TI - Histamine-induced constriction of canine peripheral lung: an airway or tissue response? AB - We compared the histamine responsiveness of peripheral airways (less than 6.0 mm diam) and parenchymal tissues in eight anesthetized paralyzed open-chest mongrel dogs. We measured pressure in a peripheral bronchus by using an antegrade wedged catheter and pressure in the alveolar region subtended by the wedged bronchus by using an alveolar capsule. Sinusoidal volume oscillations at a frequency of 0.5 Hz were delivered by a linear motor pump into the segment through the wedged catheter. We calculated the resistance of the segment (Rseg) and partitioned Rseg into tissue viscance (i.e., proportional to the resistive pressure drop between the alveolus and the pleura) and peripheral airway resistance. Measurements were taken under baseline conditions and after delivery of increasing concentrations of aerosolized histamine (0.1 micrograms/ml to 100.0 mg/ml) into the segment. We found that the histamine responsiveness of the peripheral airways and lung tissues varied markedly within a given dog. In four of eight dogs the airways were more responsive to histamine, in three of eight the tissues were more responsive, and in one of eight the response was equivalent at the two sites. We conclude that in a given animal, there is marked heterogeneity in the histamine responsiveness of the peripheral airways and parenchymal tissues and that either may dominate responsiveness in the peripheral lung. PMID- 1917752 TI - Influence of posture on lung volumes and impedance of respiratory system in healthy smokers and nonsmokers. AB - In 105 adults we investigated the influence of the body positions, sitting with respect to supine, on lung volumes and on the input resistance, (Rrs) and reactance (Xrs) of the respiratory system. Rrs and Xrs were measured between 2 and 26 Hz by means of a forced oscillation technique. Vital capacity (VC) and expiratory reserve volume (ERV) are smaller in the supine position; this reduction decreases with age and is less for ERV in male smokers than in nonsmokers. The Rrs values are larger in the supine position, and the slope of the Rrs-frequency curves tends to become less positive or negative, depending on sex, age, and smoking habits. Xrs decreases at lower frequencies. The changes in Rrs due to posture are larger in young smokers than in young nonsmokers. This is not explained by changes in ERV and may reflect changes in the intrinsic properties of the airways induced by smoking. PMID- 1917753 TI - O2 and rat pulmonary artery tone: effects of endothelium, Ca2+, cyanide, and monocrotaline. AB - The present study examines the influence of the endothelium (E), Ca2+ concentration, cyanide and monocrotaline (MCT) pretreatment on the responses of isolated rat hilar pulmonary arterial rings (PA) to hypoxia. In PA precontracted with phenylephrine, hypoxia induced an initial E-dependent relaxation phase followed by an E-independent transient contraction and a final relaxation. An increase in Ca2+ concentration from 1.5 to 2.5 mM produced an E-dependent reduction in tone generation under O2 and a significant enhancement of the hypoxia-elicited initial relaxation and the transient contractile responses. Addition of cyanide (0.1 mM) to precontracted PA produced a transient contraction similar to that caused by hypoxia. Preincubation with cyanide led to inhibition of tone generation and abolition of the contraction to hypoxia. However, the final relaxation response to hypoxia was not inhibited by cyanide. Thus, hypoxia produces an E-independent contraction via a mechanism that appears also to be activated by cyanide, and this response is not altered by MCT. The endothelium alters the response to hypoxia in a Ca(2+)-dependent manner. PMID- 1917754 TI - Role of the sympathetic nervous system in cold-induced hypertension in rats. AB - Hypertension develops in rats exposed chronically to cold [6 +/- 2 degrees C (SE)] and includes both an elevation of mean arterial pressure and cardiac hypertrophy. Previous studies suggest that cold-exposed animals, at least initially, have a large sustained increase in the activity of their sympathetic nervous system, suggesting a failure of the baroreceptor system to provide sufficient negative feedback to the central nervous system. The present study was designed to investigate whether alterations in the activity of the sympathetic nervous system, including the baroreceptor reflex, occur during exposure to cold and whether they contribute to cold-induced hypertension. Twenty male rats were prepared with indwelling catheters in the femoral artery and vein. Ten of the rats were exposed to cold (6 +/- 2 degrees C) chronically, while the remaining 10 were kept at 26 +/- 2 degrees C. Withdrawal of arterial blood samples (less than 5 ml/kg), measurement of direct arterial pressures, and measurement of baroreflex function were carried out at 0800 h at intervals throughout the experiment. Norepinephrine and epinephrine concentrations in plasma were also determined at intervals throughout the experiment. Systolic, diastolic, and mean blood pressures of cold-exposed rats were increased to levels significantly above those of controls. The sensitivity of the baroreflex (delta heart period/delta mean arterial pressure) was decreased in the cold-treated group. The concentration of norepinephrine in plasma increased after 24 h of exposure to cold and remained elevated throughout the experiment, whereas the concentration of epinephrine in plasma increased initially but returned to control levels after 19 days of exposure to cold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917755 TI - Effect of thoracic duct drainage on hydrostatic pulmonary edema and pleural effusion in sheep. AB - Positive end-expiratory pressure (PEEP) increases central venous pressure, which in turn impedes return of systemic and pulmonary lymph, thereby favoring formation of pulmonary edema with increased microvascular pressure. In these experiments we examined the effect of thoracic duct drainage on pulmonary edema and hydrothorax associated with PEEP and increased left atrial pressure in unanesthetized sheep. The sheep were connected via a tracheostomy to a ventilator that supplied 20 Torr PEEP. By inflation of a previously inserted intracardiac balloon, left atrial pressure was increased to 35 mmHg for 3 h. Pulmonary arterial, systemic arterial, and central venous pressure as well as thoracic duct lymph flow rate were continuously monitored, and the findings were compared with those in sheep without thoracic duct cannulation (controls). At the end of the experiment we determined the severity of pulmonary edema and the volume of pleural effusion. With PEEP and left atrial balloon insufflation, central venous and pulmonary arterial pressure were increased approximately threefold (P less than 0.05). In sheep with a thoracic duct fistula, pulmonary edema was less (extra-vascular fluid-to-blood-free dry weight ratio 4.8 +/- 1.0 vs. 6.1 +/- 1.0; P less than 0.05), and the volume of pleural effusion was reduced (2.0 +/- 2.9 vs. 11.3 +/- 9.6 ml; P less than 0.05). Our data signify that, in the presence of increased pulmonary microvascular pressure and PEEP, thoracic duct drainage reduces pulmonary edema and hydrothorax. PMID- 1917756 TI - Inhibition of pulmonary surfactant function by phospholipases. AB - Previous studies have shown that respiratory failure associated with disorders such as acute pancreatitis correlates well with increased levels of phospholipase A2 (PLA2) in lung lavages and that intratracheal administration of PLA2 generates an acute lung injury. In addition, bacteria such as Pseudomonas have been shown to secrete phospholipase C (PLC). We studied the effects of these phospholipases on pulmonary surfactant activity using a pulsating bubble surfactometer. Concentrations greater than or equal to 0.1 unit/ml PLA2 destroyed surfactant biophysical activity, increasing surface tension at minimum bubble size from less than 1 to 15 mN/m. This surfactant inactivation was predominantly related to the effect of lysophosphatidylcholine on the surface film, although the fatty acids released with higher PLA2 concentrations also had a detrimental effect on surfactant function. Similarly, as little as 0.1 unit PLC increased the surface tension at minimal size of an oscillating bubble from less than 1 to 15 mN/m, an effect that could be mimicked by the addition of dipalmitin to surfactant in the absence of PLC. Moreover, lower, noninhibitory concentrations (0.01 unit/ml) of PLA2 and PLC increased the sensitivity of surfactant to other inhibitory agents, such as albumin. Thus, relatively low concentrations of PLC and PLA2 can cause severe breakdown of surfactant function and may contribute significantly to some forms of lung injury. PMID- 1917757 TI - Effects of pulmonary restriction on hypercapnic responses of heart-lung transplant recipients. AB - Previous studies of hypercapnic ventilatory responses (HCVR) in human heart-lung transplant recipients (HLTX) have yielded conflicting results. We compared the HCVR of restricted transplant recipients (HLTX-R) to recipients with normal pulmonary function (HLTX-N), and normal controls (C). HLTX-R exhibited limited tidal volume responses, whereas their frequency responses were essentially identical to those of other subjects. Accordingly, HCVR of HLTX-R (1.45 +/- 0.59 l.min-1.Torr CO2(-1)) were significantly depressed compared with both HLTX-N and C (2.90 +/- 0.55 vs 3.05 +/- 1.23, respectively) (P less than 0.02). Despite undoubtedly greater ventilatory impedances, airway (mouth) occlusion pressure responses (Pm0.1) during hypercarbia of HLTX-R (0.46 +/- 0.28 cmH2O) were similar to those of C (0.43 +/- 0.20) and paradoxically blunted compared with HLTX-N (0.83 +/- 0.36) (P less than 0.02). We conclude that pulmonary reflexes are superfluous for maintenance of HCVR in HLTX with normal respiratory mechanics, whereas the presence of moderate restriction results in profound depression of CO2 responses among these subjects. PMID- 1917758 TI - Mechanisms of hypophosphatemia in humans with heatstroke. AB - Hypophosphatemia is common in heatstroke, but little is known about its mechanism. We investigated 10 consecutive patients with heatstroke (mean age 58 +/- 2 yr) whose mean rectal temperature at admission was 42.3 +/- 0.2 degrees C. Eight patients presented with hypophosphatemia [0.48 +/- 0.08 mmol/l, normal range (NR) 0.8-1.4 mmol/l], associated with increased fractional excretion of phosphate (19.8 +/- 6.4%, NR 6-20%) relative to plasma phosphate levels and reduced renal threshold for phosphate (0.55 +/- 0.08 mmol/l glomerular filtrate, NR 0.8-1.4 mmol/l). Plasma parathyroid hormone (75.0 +/- 5 pmol/l) and calcium (2.24 +/- 0.02 mmol/l) levels and fractional excretion of calcium were normal (1.66 +/- 0.27%). There was no evidence of uricosuria or aminoaciduria, and only one patient had glucosuria. Arterial carbon dioxide was decreased in eight patients (28 +/- 1.1 Torr); however, none had elevated blood pH (7.35 +/- 0.02). The results suggest that heatstroke-related hypophosphatemia is associated with abnormal phosphaturia independent of the parathyroid hormone level, and there is no evidence of tubular dysfunction. PMID- 1917760 TI - Simple validation for the hepatic venous cannula implanted chronically in conscious rats. AB - A method for the detection of vena caval contamination in blood taken from hepatic venous cannulas in conscious rats was described. The procedures included 1) bolus injection of tritiated water (50 microCi) through a cannula into the abdominal inferior vena cava and 2) continuous blood sampling (less than 0.2 ml) from the hepatic venous cannula for 2 min into a 180-cm piece of Tygon tubing, starting concurrently with tracer injection. The washout of tritium was determined from samples in 15-cm sections of Tygon tubing. Because circulation from the inferior vena cava to the hepatic vein is interceded by the systemic circulation, the washout of tritium from a valid hepatic venous cannula should resemble the pattern determined elsewhere in the systemic circulation. In the current study, the reference systemic washout was determined in the superior vena cava of a group of rats similarly injected with tritiated water in the inferior vena cava. The maximum of tritium washout derived from a valid hepatic venous cannula should fall in the range encompassed by one standard deviation of the mean of the maximum of the reference (1,400 to 1,930 cpm/sample). The maximum of the washout pattern derived from the invalid cannula, which lay adjacent to the site of injection, was expected to exceed this range. On the basis of these criteria, hepatic blood flow (HBF) was determined by sulfbromophthalein (BSP) extraction in groups of rats with valid and invalid cannulas. HBF in rats with valid hepatic venous cannulas was 2.58 +/- 0.15 in the conscious state and 2.76 +/- 0.26 ml.min-1.g wet wt-1 in the ketamine-anesthetized state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917759 TI - Decreased reliance on lactate during exercise after acclimatization to 4,300 m. AB - We hypothesized that the increased exercise arterial lactate concentration on arrival at high altitude and the subsequent decrease with acclimatization were caused by changes in blood lactate flux. Seven healthy men [age 23 +/- 2 (SE) yr, wt 72.2 +/- 1.6 kg] on a controlled diet were studied in the postabsorptive condition at sea level, on acute exposure to 4,300 m, and after 3 wk of acclimatization to 4,300 m. Subjects received a primed-continuous infusion of [6,6-2D]glucose (Brooks et al. J. Appl. Physiol. 70:919-927, 1991) and [3 13C]lactate and rested for a minimum of 90 min followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the sea level peak O2 consumption (VO2peak; 65 +/- 2% of both acute altitude and acclimatization). During rest at sea level, lactate appearance rate (Ra) was 0.52 +/- 0.03 mg.kg 1.min-1; this increased sixfold during exercise to 3.24 +/- 0.19 mg.kg-1.min-1. On acute exposure, resting lactate Ra rose from sea level values to 2.2 +/- 0.2 mg.kg-1.min-1. During exercise on acute exposure, lactate Ra rose to 18.6 +/- 2.9 mg.kg-1.min-1. Resting lactate Ra after acclimatization (1.77 +/- 0.25 mg.kg 1.min-1) was intermediate between sea level and acute exposure values. During exercise after acclimatization, lactate Ra (9.2 +/- 0.7 mg.kg-1.min-1) rose from resting values but was intermediate between sea level and acute exposure values. The increased exercise arterial lactate concentration response on arrival at high altitude and subsequent decrease with acclimatization are due to changes in blood lactate appearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917761 TI - Methods for intracellular recording from hippocampal brain slices under high helium pressure. AB - A method for intracellular recording from rat hippocampal brain slices under helium pressure is described. The preparation is mounted on a horizontal mobile platform that is rolled into the pressure chamber and can be viewed at pressure. Remote manipulation of the glass microelectrodes is achieved by a high-resolution electrically driven commercially available system. The slice is superfused continuously from a closed system within the chamber. Temperature is maintained at 37 degrees C and PO2 at 0.5 atm within the pressure chamber. A pressure of 200 ATA can be obtained, although thus far recordings have been made up to only 130 ATA. The experiments demand that a number of sample recordings be made from the same slice at both ambient and high pressure, and tests have proved that, although difficult, this can be achieved. The resting membrane potential, the current-voltage relationship, and the action potential responses to short (8 ms), medium (80 ms), and long (800 ms) depolarizing current pulses have all been measured in CA1 pyramidal neurons. PMID- 1917762 TI - Training-induced muscle enlargement. PMID- 1917763 TI - Cyclooxygenase inhibitors prevent ethchlorvynol-induced injury in rat and rabbit lungs. AB - The effect of three chemically dissimilar cyclooxygenase inhibitors on ethchlorvynol-(ECV) induced acute lung injury was studied in isolated buffer perfused rat and blood-perfused rabbit lungs. ECV caused the microvascular fluid filtration coefficient (Kf) to increase by greater than threefold in the rat lungs and twofold in the rabbit lungs. ECV caused increased pulmonary vascular resistance (PVR) and microvascular pressure measured by the double occlusion technique (Pdo) compared with the vehicle control group in the rat experiments. However, ECV had no effect on PVR or Pdo in the rabbit experiments. Pretreatment with the cyclooxygenase inhibitors indomethacin, ibuprofen, and meclofenamate prevented the increase in microvascular permeability in both the rat and rabbit lung preparations. The cyclooxygenase inhibitors also prevented the ECV-induced PVR and Pdo increases in the rat lungs but had no effect on PVR or Pdo in the rabbit lungs. These results indicate that cyclooxygenase products of arachidonate metabolism mediate the ECV-induced Kf increase in both isolated rat and rabbit lungs. PMID- 1917764 TI - Tracheal vascular and smooth muscle responses to air temperature and humidity in dogs. AB - Twenty-five dogs were anesthetized, paralyzed, and artificially ventilated. Their cranial tracheal arteries were perfused bilaterally with blood at constant flow, and the perfusion pressures (Patr) were measured. Tracheal smooth muscle function was assessed by recording changes in external diameter (delta Dtr). The perfused segment of the trachea was exposed to air at a constant unidirectional airflow of 25 l/min. Group 1 (n = 6) was exposed to cold dry air, ambient room air, and hot dry and hot humid air, each for 10 min with exposures starting from zero flow. The tracheal vascular responses to all four conditions were small vasodilations (delta Patr from -2 to -6%) followed by recovery or small vasoconstrictions. In group 2 (n = 19), exposures to cold dry and hot humid air were preceded and followed by body-temperature fully humidified air. Cold dry air caused a sustained vasodilation (delta Patr -9.0 +/- 1.1%), and hot humid air usually caused a biphasic response: a vasoconstriction (delta Patr 4.4 +/- 1.0%) followed by a vasodilation (delta Patr -5.7 +/- 1.9%). The warm humid air after cold dry air or hot humid air caused a further vasodilation, which lasted a short time after cold dry air (delta Patr -3.7 +/- 0.4%) but greater than 10 min after hot humid air (delta Patr -13.8 +/- 1.4%). In both groups, all exposures that cooled the trachea (cold dry air, ambient room air, and hot dry air) caused smooth muscle contraction, and hot humid air that warmed the trachea caused relaxation. PMID- 1917765 TI - Heat debt during cold air exposure before and after cold water immersions. AB - Acclimation to cold can manifest itself in several different ways, insulative and metabolic being the most common. Bittel (J. Appl. Physiol. 62: 1627-1634, 1987) has demonstrated that heat debt, which encompasses both heat production and heat loss, can be used as a unitary index of acclimation. However, conflicting results are obtained if heat debt is calculated using a mean-weighted body temperature (Tb) vs. the change of body heat content through the integration of heat storage (S). The present study examines the determination of heat debt by three methods of calculation, the first based on Tb and the other two based on S where heat losses are measured in one and predicted in the other. Data were obtained from five healthy young males exposed to 10 degrees C air for 2 h on four different occasions. The first two exposures provided control data, while the last two were performed after 5 and 10 days, respectively, of daily immersions in 15 degrees C water to induce acclimation. The variability in response between the control exposures was as large as that among the other exposures. Although the method of calculation using Tb indicated that subjects were close to a thermal balance after 2 h of cold air exposure, this contrasted sharply with the result of the other two methods that indicated heat debt was still increasing steadily. The latter two methods are considered more accurate for transient heat debt calculation. Although cases of individual acclimation were found, these were different among the subjects, resulting in pooled responses that indicated no group acclimation by means of any of the three methods of calculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917766 TI - Nonlinearity and harmonic distortion of dog lungs measured by low-frequency forced oscillations. AB - The nonlinearity of lung tissues and airways was studied in six anesthetized and paralyzed open-chest dogs by means of 0.1-Hz sinusoidal volume forcing at mean transpulmonary pressures (Ptp) of 5 and 10 cmH2O. Lung resistance (RL) and elastance (EL) were determined in a 32-fold range (15-460 ml) of tidal volume (VT), both by means of spectrum analysis at the fundamental frequency and with conventional time-domain techniques. Alveolar capsules were used to separate the tissue and airway properties. A very small amplitude dependence was found: with increasing VT, the frequency-domain estimates of RL decreased by 5.3 and 14%, whereas EL decreased by 20 and 22% at Ptp = 5 and 10 cmH2O, respectively. The VT dependences of the time-domain estimates of RL were higher: 10.5 and 20% at Ptp = 5 and 10 cmH2O, respectively, whereas EL remained the same. The airway resistance increased moderately with flow amplitude and was smaller at the higher Ptp level. Analysis of the harmonic distortions of airway opening pressure and the alveolar pressures indicated that nonlinear harmonic production is moderate even at the highest VT and that VT dependence is homogeneous throughout the tissues. In three other dogs it was demonstrated that VT dependences of RL and EL were similar in situ and in isolated lungs at both Ptp levels. PMID- 1917767 TI - Effect of lung inflation on regional lung expansion in supine and prone rabbits. AB - At functional residual capacity, lung expansion is more uniform in the prone position than in the supine position. We examined the effect of positive airway pressure (Paw) on this position-dependent difference in lung expansion. In supine and prone rabbits postmortem, we measured alveolar size through dependent and nondependent pleural windows via videomicroscopy at Paw of 0 (functional residual capacity), 7, and 15 cmH2O. After the chest was opened, alveolar size was measured in the isolated lung at several transpulmonary pressures (Ptp) on lung deflation. Alveolar mean linear intercept (Lm) was measured from the video images taken in situ. This was compared with those measured in the isolated lung to determine Ptp in situ. In the supine position, the vertical Ptp gradient increased from 0.52 cmH2O/cm at 0 cmH2O Paw to 0.90 cmH2O/cm at 15 cmH2O Paw, while the vertical gradient in Lm decreased from 2.17 to 0.80 microns/cm. In the prone position, the vertical Ptp gradient increased from 0.06 cmH2O/cm at 0 cmH2O Paw to 0.35 cmH2O/cm at 15 cmH2O Paw, but there was no change in the vertical Lm gradient. In anesthetized paralyzed rabbits in supine and prone positions, we measured pleural liquid pressure directly at 0, 7, and 15 cmH2O Paw with dependent and nondependent rib capsules. Vertical Ptp gradients measured with rib capsules were similar to those estimated from the alveolar size measurements. Lung inflation during mechanical ventilation may reduce the vertical nonuniformities in lung expansion observed in the supine position, thereby improving gas exchange and the distribution of ventilation. PMID- 1917768 TI - Effects of anesthetic agents on systemic critical O2 delivery. AB - The present study tested the hypothesis that anesthetic agents can alter tissue O2 extraction capabilities in a dog model of progressive hemorrhage. After administration of pentobarbital sodium (25 mg/kg iv) and endotracheal intubation, the dogs were paralyzed with pancuronium bromide, ventilated with room air, and splenectomized. A total of 60 dogs were randomized in 10 groups of 6 dogs each. The first group served as control (C). A second group (P) received a continuous infusion of pentobarbital (4 mg.kg-2.h-2), which was started immediately after the bolus dose. Three groups received enflurane (E), halothane (HL), or isoflurane (I) at the end-tidal concentration of 0.7 minimum alveolar concentration (MAC). The sixth group received halothane at the end-tidal concentration of 1 MAC (HH). Two groups received intravenous alfentanil at relatively low dose (AL) or high dose (AH). The last two groups received intravenous ketamine at either relatively low dose (KL) or high dose (KH). In each group, O2 delivery (Do2) was progressively reduced by hemorrhage. At each step, systemic Do2 and O2 consumption (VO2) were measured separately and the critical point was determined from a plot of Vo2 vs. Do2. The critical O2 extraction ratio (OER) in the control group was 65.0 +/- 7.8%. OER was lower in all anesthetized groups (P, 44.3 +/- 11.8%; E, 47.0 +/- 7.7%; HL, 45.7 +/- 11.2%; I, 44.3 +/- 7.1%; HH, 33.7 +/- 6.0%; AL, 56.5 +/- 9.6%; AH, 43.5 +/- 5.9%; KH, 57.7 +/- 7.1%), except in the KL group (78.3 +/- 10.0%). The effects of halothane and alfentanil on critical OER were dose dependent (P less than 0.05), whereas critical OER was significantly lower in the KH than in the KL group. Moreover, the effects of anesthetic agents on critical Do2 appeared related to their effects on systemic vascular resistance. Anesthetic agents therefore alter O2 extraction by their peripheral vascular effects. However, ketamine, with its unique sympathetic stimulant properties, had a lesser effect on OER than the other anesthetic agents. It could therefore be the anesthetic agent of choice in clinical situations when O2 availability is reduced. PMID- 1917769 TI - A new method to measure nasal impedance in spontaneously breathing adults. AB - As an alternative to standard rhinomanometric methods, we applied forced oscillations at the mouth in five normal subjects and determined their nasal impedance with a novel method involving flow subtraction. Pressure oscillations of constant amplitude were applied at the mouth of a subject both when the nostrils were open and when they were closed with a noseclip. The airflows measured under the two conditions were subtracted to yield the oscillating nasal airflow at the imposed pressure. The resultant pressure-flow relation defined the nasal impedance of the subject. For frequencies between 3 and 15 Hz, the transnasal pressure-flow relation was well described by a linear lumped parameter model consisting of a resistive and inertial element. Nasal resistance obtained with flow subtraction did not differ significantly from control measurements obtained while the subjects performed the Valsalva maneuver. In contrast, nasal inertance obtained with flow subtraction was approximately twice that obtained with the Valsalva method. The difference between inertances may reflect structural changes in nasopharyngeal dimensions that occur with the Valsalva maneuver. We conclude that the mechanical impedance of the nasal passage may be determined during spontaneous breathing from the response to imposed forced oscillations at the mouth. The noninvasive nature of this method suggests that it may be simpler to implement than traditional rhinomanometric methods. PMID- 1917770 TI - Estimation of the pulmonary microvascular reflection coefficient to protein in dogs. AB - We used a new technique to estimate the pulmonary microvascular membrane reflection coefficient to plasma protein (sigma d) in anesthetized dogs. In five animals we continuously weighed the lower left lung lobe and used a left atrial balloon to increase the pulmonary microvascular pressure (Pc). We determined the relationship between the rate of edema formation (S) and Pc and estimated the fluid filtration coefficient (Kf) as delta S/delta Pc. From the S vs. Pc relationship and Kf, we estimated the Pc at which S/Kf = 10 mmHg for each dog. This pressure (P10) was 38.0 +/- 5.8 (SD) mmHg, and the plasma protein osmotic pressure (pi c) was 14.9 +/- 3.7 mmHg. In five additional dogs in which we decreased pi c to 2.9 +/- 1.7 mmHg, P10 = 27.2 +/- 2.6 mmHg. The P10 vs. pi c regression line fit to the data from all 10 dogs was P10 = 0.92 pi c +/- 24.4 mmHg (r = 0.88). We estimated sigma d from the slope of the regression line as sigma d = square root of delta P10/delta pi c. With this technique, we estimated that, with 95% probability, sigma d lies between 0.72 and unity. This is higher than most previous sigma d estimates. PMID- 1917772 TI - Structure of physical performance in occupational tasks. AB - Two lines of research concerning the dimensionality of physical performance in occupational tasks are described. In the first, the physical requirements of tasks are analyzed as reflected in job analyses. In the second, the structure of physical abilities tests used to predict performance in physically demanding jobs is evaluated. Principal components analyses of both job analysis and test performance data suggest that the structure of physical abilities has three major components--strength, endurance, and movement quality. This structure appears to be independent of job type or level of incumbents' performance. PMID- 1917771 TI - Active lymphatic pumping and sheep lung lymph flow. AB - Active (intrinsic) lymphatic pumping may be an important factor determining lymph flow from the lungs. Unfortunately, in most experiments, it is very difficult to determine the influence of active pumping vs. passive factors on lymph flow. However, 1) the pumping activity (stroke volume and frequency) of isolated lymphatic segments varies nonlinearly with transmural pressure, and 2) the lung lymph flow from awake sheep varies nonlinearly with lymphatic outflow pressure. Accordingly, if lymphatic pumping significantly influences lung lymph flow, then it should be possible to describe the sheep lung lymph flow vs. outflow pressure data with the pumping activity data. To test this, we used published lymphatic pumping activity data to develop a mathematical model of the lymphatic pump for a segment of lymphatic vessel. Flow vs. outflow pressure relationships obtained from simulations with this model were very similar to the data from sheep. Our results indicate that both passive factors and active lymphatic pumping contribute to lymph flow, and our model may allow investigators to distinguish the effects of active pumping vs. passive factors in the regulation of lymph flow. PMID- 1917773 TI - Other-race face perception. AB - The other-race effect (or own-race bias or cross-racial identification effect) refers to the finding that recognition memory tends to be better for faces of members of subjects' own race than for faces of members of other races. The current study was designed to test the hypothesis that perceptual skills specific to identifying faces of particular racial groups contribute to this effect. On each of 50 trials, a photograph of a face was tachistoscopically presented for 120 ms, followed by a pattern mask and then a plain-view test pair composed of the previously presented face and a matched foil. As predicted, an other-race effect was obtained on this perceptual task: White subjects performed significantly more poorly on trials involving African American faces than on trials involving White faces, whereas no such difference was obtained among African American subjects. PMID- 1917774 TI - Stage-dependent alteration of negative charges of uninfected erythrocytes in Plasmodium falciparum culture. PMID- 1917775 TI - Leukemic cells on melamine substrate foils. PMID- 1917776 TI - Iron is deleterious to hormone-responsive pituitary cell growth in serum-free defined medium. PMID- 1917777 TI - Cytogenetic damage and cytokinetics in streptonigrin-treated human lymphocytes. PMID- 1917778 TI - A cell line of human malignant astrocytoma producing autocrine growth factor. AB - A cell line was established from an anaplastic astrocytoma from a 69-yr-old female. The cells have been serially subcultured over 300 times for 6 yr without showing any sign of cell senescence. Their doubling time is about 36 h. The cells are fusiform and often hexagonal in sparse culture, but become spindle-shaped and formed mosaic structure in confluent culture. Under electron microscopy, intermediate filaments were randomly distributed in the cytoplasma, especially in the perinuclear space. The chromosome number was near tetraploid and varied from 86 to 94 chromosomes with a modal number of 91. The alpha and beta subunits of S 100 protein, vimentin, and glial fibrillary acidic protein (GFAP), which are reliable markers of astrocytic cells, were demonstrated in a large number of cells by immunoperoxidase staining. The results of immunoblotting showed that the expression of vimentin was much higher than that of GFAP. The tumorigenicity of the cells was revealed by xenografting into nude mice, which were X-irradiated before inoculation. Culture medium conditioned by the cells promoted growth of these cells in serum-free conditions and of normal rat glial cells in serum depleted culture. The growth-promoting effect of conditioned medium was lost by trypsinization and reduced by boiling. These findings suggest that these cells are derived from neoplastic astrocytic cells and secrete a self-acting polypeptide growth-promoting factor into the culture medium. PMID- 1917779 TI - Isolation and characterization of mouse neural precursor cells in primary culture. AB - Primary cultures of mouse neural precursor cells were established by enzymatic dissociation of embryonic Day 10 fetal heads followed by negative selection of non-neural contaminating cells. The latter were allowed to attach and spread on a plastic substrate under conditions that permitted neural precursor cells to remain suspended in the culture medium. The resulting neuroepithelial cell enriched suspension then was plated on dishes coated with poly-D-lysine. Growth of fibroblastic cells was inhibited in a selective medium. Cell proliferation was measured by immunoperoxidase staining of nuclei after bromodeoxyuridine labeling. The proportion of labeled cells declined from 50% on Day 1 until Day 5 when it approached zero, and after 7 days in culture a fourfold increase in cell number was achieved in medium containing 1% fetal bovine serum, transferrin, insulin, cholera toxin, and sodium selenite. Differentiation of neural precursor cells was studied by indirect immunofluorescence microscopy for the appearance of neuron- and astrocyte-specific cytoskeletal proteins at successive intervals in culture. Cells bearing neuritic processes and expressing neurofilaments as well as microtubule-associated protein 2 were present in low numbers on Day 1, increasing through Day 14. Stellate cells with morphologic features of astrocytes and immunoreactive for glial fibrillary acidic protein were not detected until Day 5 and did not become abundant until Day 11. No differences in morphology or immunocytochemical staining characteristics were found between neural precursor cells processed by enzymatic dissociation of whole fetal heads and those recovered by manual dissection of fetal neuroepithelia. The large number of neural precursor cells obtained by this rapid, simple method makes possible the production of mass cultures for molecular analysis of the regulatory factors that control proliferation and differentiation during early development of the mouse central nervous system. PMID- 1917780 TI - Toxicity in vital fluorescence microscopy: effect of dimethylsulfoxide, rhodamine 123, and DiI-low density lipoprotein on fibroblast growth in vitro. AB - Fluorescence microscopy performed on living cells is a valuable technique for elucidating patterns of cell growth in vitro over artificial biomaterials such as vascular grafts, and for in vivo studies such as identification and treatment of atherosclerotic plaques. Two fluorescent dyes of particular value for vital fluorescence studies are Rhodamine-123 and 3,3'-dioctadecylindocarbocyanine labeled low density lipoprotein (DiI-LDL). We examined the toxicity of these two dyes and of dimethylsulfoxide (DMSO), a solvent used in Rhodamine-123 studies, on the growth of MRC5 human fetal fibroblasts in monolayer culture. Two parameters of cell growth were quantitated: Cell number (a measure of proliferation), and cell area (a measure of cell spreading), based on microscopic images obtained at the start and end of a 48-h growth period after brief exposure (0.5 h) to test solutions. We found that the recommended solvent for solubilization of Rhodamine 123, DMSO, caused cessation of cell proliferation and actual reduction in the area covered by adherent fibroblasts at concentrations of as low as 0.1% (vol:vol). Rhodamine-123 made up from an aqueous stock solution modestly retarded proliferation and spreading, and there was no significant effect of DiI-LDL on these parameters over prolonged periods of exposure (up to 24 h) in culture. These results demonstrate that the most toxic substance for growing fibroblasts was the solvent DMSO. We conclude that both the solvent vehicle and fluorescent dye should be carefully examined for potential toxicity before such dyes are used for vital fluorescence studies of living cells. PMID- 1917781 TI - Stimulation of proliferation of bovine placental cells by products of activated mononuclear leukocytes. AB - Culture medium conditioned with concanavalin A-stimulated mononuclear leukocytes was tested for its ability to stimulate in vitro proliferation of bovine placental cells. The crude preparation of cytokines caused a dose-dependent increase in [3H]thymidine uptake into cells obtained by trypsinization of fresh bovine placentae and placental cell lines established from cellular outgrowths of long-term bovine placental cultures, but had no effect on growth of 3T3 fibroblasts. Growth of trypsinized placental cells was not enhanced by culture in the presence of interleukin-2, interferon-beta 2, interferon-gamma, or tumor necrosis factor-alpha. These results corroborate those of murine studies, suggesting a growth-promoting role for cytokines released into the maternal-fetal interface. PMID- 1917782 TI - DNA fingerprinting with oligonucleotides can differentiate cell lines derived from the same tumor. AB - Oligonucleotide fingerprinting was applied to investigate the relatedness of several cell lines that were established between 1973 and 1977 from a teratocarcinoma. We were able to distinguish cell lines derived at different times. In addition, sublines from one cell line (PYS-2) could be discriminated by using a combination of different probes. Therefore multilocus fingerprinting with oligonucleotides is a useful method for monitoring changes in cell lines kept in culture for many generations. PMID- 1917783 TI - Accumulation of pyrroline 5-carboxylic acid in conditioned medium of cultured fibroblast: stimulatory effects of serum, insulin, and IGF-1. AB - Pyrroline 5-carboxylate, an intermediate of amino acid metabolism, is released into medium by cultured normal human fibroblasts. With cells made quiescent by serum starvation, the addition of 10% fetal bovine serum augmented the release of pyrroline 5-carboxylate into medium by 2.5-fold. Although platelet-derived growth factor was without effect, both insulin and insulinlike growth factor-1 nearly reproduced the serum effect. The dose-dependence of insulin and insulinlike growth factor 1 effects suggested their mediation by their own respective receptors. Although the mechanism for the stimulatory effect remains unknown, these effects of insulin and insulinlike growth factor 1 on pyrroline 5 carboxylate suggest hormonal regulation of pyrroline 5-carboxylate release. PMID- 1917784 TI - Partial trisomies in two spontaneously arising long-lived human keratinocyte lines. AB - During experiments concerning the introduction of oncogenes into normal human keratinocytes, we observed long-lived colonies arising spontaneously at the same low frequency in control cultures as in those transfected with Ha-rasEJ or activated c-myc or both. Two of these were karyotyped early in their life span and showed additional chromosomal material on the short arm of chromosome 9 in one case and of chromosome 18 in the other, whereas the parental cells had a normal karyotype. This indicates the presence of a partial trisomy in each line, although the origin of the extra chromosomal material is not known. A similarly long-lived human keratinocyte line containing an isochromosome of the long arm of chromosome 8 has been described elsewhere. Together these results suggest that the spontaneous occurrence of long-lived lines is more common in human keratinocytes than in fibroblasts and that a triple dose of one or more genes may be the initial event in this process. PMID- 1917785 TI - Protamine stimulates serum-free growth of human muscle cells. PMID- 1917786 TI - A new eccrine ductal adenocarcinoma cell line, UISO-ADN-1. PMID- 1917787 TI - Cystic fibrosis and control nasal epithelial cells harvested by a brushing procedure. PMID- 1917788 TI - Endothelial and smooth muscle cells from the same rat aorta. PMID- 1917790 TI - Cell-to-cell signaling in the regulation of procollagen expression in primary avian tendon cells. AB - High cell density is required for high procollagen expression (50% of total protein synthesis) in primary avian tendon (PAT) cells but the signaling mechanism that triggers this response has been difficult to decipher. By using a quantitative in situ hybridization assay for procollagen mRNA, cell density dependent changes in procollagen expression can be followed at the single cell level. PAT cells can then be shown to respond to the presence of their neighbors over approximately 1-mm distance. The cell density signal remains effective independent of the medium volume to cell ratio but becomes sensitive to dispersion and dilution when the medium is agitated. PAT cells respond to a reduction in cell density, when neighboring cells are scraped away, by outgrowth (approximately 1 mm) and reestablishment of a cell density gradient in cellular procollagen mRNA levels. However, removing neighboring cells while preventing migration off of their own extracellular matrix retards the drop in procollagen mRNA levels. The evidence, taken as a whole, is consistent with a model whereby the cell density signal is a loosely bound component of the cell layer thereby restricting its diffusion to two dimensions but making it susceptible to dispersion by medium agitation. PMID- 1917789 TI - Extracellular matrix permits the expression of von Willebrand's factor, uptake of di-I-acetylated low density lipoprotein and secretion of prostacyclin in cultures of endothelial cells from rat brain microvessels. AB - Microvascular endothelial cells from the adult rat brain were cultured on Matrigel and found to express many differentiated properties including secretion of prostacyclin (PGI2) and von Willebrand's factor (vWF). Brain microvascular endothelial cells (BMECs) were purified by dextran and percoll gradients after enzymatic treatment and cultured under various conditions. BMECs that were plated on Matrigel stained positively for factor VIII-related antigen and incorporated Di-I-acetylated low density lipoprotein, whereas BMEC plated on fibronectin, gelatin, or uncoated dishes did not express any of the above properties which are characteristic of endothelial cells. vWF was measured by a sensitive ELISA in the culture media of BMECs plated on different types of matrices. Specificity of the anti-human vWF antibodies for the rat vWF was verified by immunoabsorption on a solid phase, sodium dodecyl sulfate, and Western blot analysis. BMECs also secreted vWF into the culture media only when the cells were plated on Matrigel, and this secretion was augmented after a 6 h incubation with an interleukin-1 tumor necrosis factor-alpha mixture, but not by lipopolysaccharide. From different matrices tested, only Matrigel permitted the secretion of PGI2 by BMECs. Cells also proved to be sensitive to mechanical stimulation and became refractory to secretagogue if the mechanical stimulation was serially repeated. Under the best conditions, stimulation of the cells with bradykinin (1 microM) substantially increased PGI2 secretion. These data indicate that growth of BMECs on Matrigel in vitro permits the expression of classical endothelial cell markers in a manner similar to the behavior of these cells in situ. PMID- 1917792 TI - Isolation of two morphologically distinct cell lines from rat arterial smooth muscle expressing high tumorigenic potentials. AB - Smooth muscle cell proliferation is an important feature of atherogenesis. Some works have hypothesized that a transformation of smooth muscle cells could arise during this pathological process. The present paper describes two spontaneously transformed cell lines of arterial smooth muscle cells (SMC) established from aortic media of adult rat. The cell lines have been designated V6 and V8; some of their morphologic, growth, and metabolic characteristics are described and compared to their parent cells. The two cell lines appeared distinct by their morphology and by their degree of transformation. V6 cells appeared as elongated spindle-shaped cells whereas V8 cells were spread cells with a cobblestone pattern. Karyotypes of both cell lines showed a high polyploidy level. V6 and V8 cell lines were immortalized and showed growth characteristics of transformed cells: low requirement of serum to grow, ability to form colonies in soft agar and tumorigenicity in nude mice; V8 cells presented a higher malignancy than V6 cells. Both V6 and V8 cells exhibited characteristics of cultured arterial SMC: ultrastructure, alpha actin expression at the protein and mRNA level, prostacyclin production. The remarkably different morphologies of the V6 and V8 lines and their transformed phenotype suggest that these cell lines could be useful models to study SMC differentiation and proliferation with respect to atherosclerotic or hypertensive vascular diseases. PMID- 1917791 TI - Functional differentiation of mouse uterine epithelial cells grown on collagen gels or reconstituted basement membranes. AB - Epithelial cells were isolated from mouse endometrium and cultured on two types of extracellular matrix, namely, rat-tail collagen (type I) gels and basement membrane extract (BME) derived from the Engelbreth-Holm-Swarm murine sarcoma. Cell attachment in serum-free medium during the initial 24 h after seeding was approximately twofold higher on BME compared with collagen type I. Addition of serum to the medium enhanced cell attachment on both matrices. On both collagen and BME, uterine cells grew as smooth-bordered colonies, and within a week of culture the cells became cuboidal to columnar in shape. Electron microscopy revealed the presence of apical microvilli associated with a glycocalyx, junctional complexes, tonofilaments, short strands of undilated endoplasmic reticulum, Golgi complex, and lipid droplets. However, cells on BME showed a higher degree of differentiation as assessed by occasional formation of small patches of basement membranelike structure subjacent to the flattened basal surface and formation of glandlike structures within the matrix. Proliferation of these cells as measured by radioactive thymidine incorporation into DNA was increased threefold by addition of epidermal growth factor (EGF) and insulin to the medium, but was not changed by 17 beta-estradiol. The expression of progesterone receptors by uterine epithelial cells grown on both matrices was doubled by addition of EGF and estradiol to the medium. PMID- 1917793 TI - L-tyrosine-binding proteins on melanoma cells. AB - Crosslinking of [14C]L-tyrosine to at least five hamster melanoma cell surface proteins is reported. This effect was abolished by addition of nonradioactive L tyrosine, L-phenylalanine, or L-dopa, but not by D-tyrosine, tyramine, dopamine, norepinephrine, or epinephrine. The above proteins can be purified by tyrosine affinity chromatography. They have molecular weights different from proteins staining for dopa oxidase and proteins that bind anti-tyrosinase antibody in Western blots. It is suggested that they may be a hithergo unrecognized part of the cellular apparatus governing melanogenesis. PMID- 1917795 TI - Heparin exercise treatment following percutaneous transluminal coronary angioplasty in a patient with effort angina. AB - A 63-year-old female with chronic stable effort angina underwent percutaneous transluminal coronary angioplasty (PTCA) for a donating coronary artery of the collateral circulation to the jeopardized region. Because of the inefficacy of the procedure in increasing the collateral flow reserve, the patient was then put on an exercise regimen and also received heparin pretreatment. Her exercise tolerance improved remarkably with the development of improved collateral circulation. PMID- 1917794 TI - Altered pattern of post-rest contractions in hypertrophied rabbit ventricle. AB - The pattern of contractions elicited after rest periods of 0.25-10 min duration was investigated in right ventricular papillary muscles from control and hypertrophied rabbit hearts. Hypertrophy was induced by pressure overload following coarctation of the pulmonary artery. In control hearts, the first post rest contraction was always of a smaller amplitude than the preceding steady state (0.5 Hz stimulation) contractions, and the amplitude of this first post rest contraction decreased as the rest interval increased. In contrast, the amplitude of the first post-rest contraction of muscles from hypertrophied hearts exceeded the steady-state amplitude for rest durations of up to at least 2 min. In the hypertrophied muscles, force in the first post-rest contraction (expressed as a percentage of the pre-rest steady-state) was potentiated compared to the control muscles at all rest intervals studied. There was no significant difference in the second post-rest contraction between control and hypertrophied muscles at any rest interval. Following the second post-rest contraction, force increased monotonically toward the steady-state levels in all the muscles. The recovery of force was, however, somewhat faster in the hypertrophied muscles. Upon resumption of 1-Hz stimulation following rest intervals of 2 min or greater, pulsus alternans were invariably observed in the hypertrophied muscles but never in the control muscles. These differences in the non-steady-state contractile behavior of ventricular muscle from normal and hypertrophied hearts are suggestive of some alteration in the normal pattern of Ca2+ translocation in pressure overload hypertrophy of rabbit ventricle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1917796 TI - Falls, sway, and symmetry of weight-bearing after stroke. AB - This study examines the relationship between falls, postural sway, stance symmetry, and length of hospital admission after stroke. Side of stroke, age, and sex differences are noted. A consecutive sample of 92 stroke patients underwent two assessments, four months apart, at between two and nine months post-stroke. Measurements of weight distribution and sway were made on the Nottingham Balance Platform. Any falls were recorded. A significant relationship was found between sway values at the first assessment and the number of falls (r = 0.27, p less than 0.01). Sway values improved with recovery (z = 2.9, p less than 0.01). Stance symmetry was significantly related to length of stay (r = 0.27, p less than 0.01) and age (r = 0.28, p less than 0.01), but not to falls. A significant difference was found between the weight distribution of right- and left-sided hemiplegias (t = 8.2, p less than 0.001) and stance symmetry improved with recovery (z = 2.9, p less than 0.01). No sex differences were apparent. This suggests that stance symmetry is another index of stroke severity, but that sway and falls frequency are not. However, an important relationship between sway and falls was revealed. PMID- 1917797 TI - Residual mobility problems after stroke. AB - At final follow-up 2-7 years after their first stroke, 328 survivors from the Oxfordshire Community Stroke Project register were assessed for mobility disability. Patients were classified as being either mobile or immobile, according to defined criteria. Of the 190 immobile patients, only 60 could be entered into a trial of physiotherapy. The major causes of attrition were refusal to participate (97 patients) and the absence of any stroke impairment causing the immobility (18). Arthritis (67) and dementia (39) were common in patients with mobility disability. Immobile patients were older and had suffered a more severe index stroke. This study stresses the relatively low frequency of long-term immobility following stroke directly due to stroke-induced impairments. PMID- 1917799 TI - Rehabilitation in a rural community in Ukraine--a pilot project. AB - The World Health Organization has promoted the concept of community-based rehabilitation as a means of fulfilling the needs of disabled persons in their home environment, and at the same time decreasing the costs of tertiary rehabilitative care. This paper reports on the 10-year experience of a village rehabilitation hospital in rural Ukraine. The hospital was converted to a rehabilitation facility by provision of rehabilitation space, training of local medical and allied health personnel in the principles of rehabilitation, provision of modalities, exercise, hydrotherapy, apiotherapy, and obtaining the necessary physical medical equipment. The cost of this conversion was quite modest and was more than compensated for by the efficient utilization of the facility in the region together with the significant saving in tertiary care costs, including travelling time for patients. PMID- 1917798 TI - Pulmonary embolism following anticoagulation therapy. AB - Five patients with traumatic spinal injury received a course of oral anticoagulant therapy with warfarin, heparin, or phenindione for 90 days following injury. These patients, on discontinuation of anticoagulant therapy, developed pulmonary embolus; two of these were confirmed by ventilation perfusion lung scintigraphy, and two were confirmed at post-mortem. The reasons for this are discussed, in particular the importance of delayed anticoagulation, obesity, operations, and mobilization in wheelchairs. The implications for further treatment are discussed. PMID- 1917800 TI - A novel EMG/video system for the analysis of movement. AB - A simple movement-analysis system is described which provides a video display of the moving image and an easily-observable EMG signal in the form of a time synchronized light-emitting-diode (LED) display. Its salient feature is the economic and meaningful way in which both data are displayed simultaneously. Its applications in the field of clinical education and training, in diagnosis, and in rehabilitation are discussed. PMID- 1917801 TI - Vocational Rehabilitation Index assessment of rehabilitation medicine service patients. AB - Only a minority of working-age patients referred to rehabilitation medicine services return to work, but could more be helped? A first step is identifying those potentially able to do so. This paper describes the retrospective application of the Vocational Rehabilitation Index (VRI) to 223 patients of working age and with various diagnoses referred to one rehabilitation medicine service. The VRI discriminates between patients who return to work and those who do not, as well as between groups with apparently differing degrees of need for vocational rehabilitation assistance. It also has good face validity. Results suggest that it is feasible to apply the VRI in rehabilitation medicine settings and that further prospective evaluation and practical applications should be undertaken. PMID- 1917802 TI - Fumigation trends, fumigant analysis, and findings. PMID- 1917803 TI - Evidence of an unusual pattern of polychlorinated biphenyls in the serum of some residents and canines in Paoli, Pennsylvania. AB - The present study uses gas liquid chromatography (GLC) electron capture detection with packed and capillary columns to detect polychlorinated biphenyls (PCBs) in serum samples from people living near the electric car repair and maintenance facility of the Southeastern Pennsylvania Transit Authority in Paoli, Pennsylvania. Most of the cohort surveyed had serum patterns similar to patterns for Aroclor 1260 (AR 1260); a small portion (3/89) had patterns indicative of an AR with higher chlorination (e.g., AR 1268). In addition to analyzing serum samples from humans, we also analyzed serum samples from canines (pets of some of the subjects). In general, the serum pattern for canines was less descriptive for AR 1260 than the pattern for humans; however, the pattern for several canines (9/16) was that of the higher chlorinated PCBs (e.g., AR 1268). By using mass spectrometry and capillary column GLC, we confirmed the presence of high molecular weight polychlorinated congeners in both human and animal samples. We were not able to show a statistically significant relationship between serum patterns of PCBs in canines and their owners or between canines and certain behavioral traits (e.g., runs free, retrieves, hours outside, hours inside). However, the correlation between PCBs quantified as AR 1268 and canines' residence time was statistically significant. PMID- 1917805 TI - Capillary gas chromatographic determination with electron capture detector of beta-propiolactone in biological materials. AB - A method has been developed for the determination of beta-propiolactone by derivatizing it to the volatile N-hexyl-3-heptafluorobutanoyloxypropanamide, which can be separated and identified by a capillary CP-Sil 8 column, and detected by an electron capture detector (ECD). First, beta-propiolactone is reacted with N-hexylamine to yield N-hexyl-3-hydroxypropanamide. The fluorobutanoyl ester derivative is next prepared by using heptafluorobutyric acid anhydride in the presence of trimethylamine. The method is very sensitive, simple, and specific, and can be used to detect and quantitate residual beta propiolactone in lyophilized biological materials. The limit of detection is 0.2 ppm beta-propiolactone in a 50 mg sample; however, because of variability at low levels, the limit of quantitation is 1 ppm. Detector response was linear for 2 500 mg beta-propiolactone. Recoveries were 98% or greater from lyophilized vaccines spiked at the 2-20 ppm level. No side products or interference peaks were observed in the derivatization reaction. PMID- 1917804 TI - Multielement concentrations in liver and kidney tissues from five species of Canadian slaughter animals. AB - The present paper describes results of a national survey conducted between 1982 and 1989 to determine residues of arsenic, cadmium, copper, mercury, lead, selenium, and zinc in Canadian slaughter animals. Liver and kidney tissues from cattle, swine, poultry, horses, calves, and sheep were tested. Arsenic was found in most avian and porcine samples, and their respective means of 0.36 and 0.26 micrograms/g in liver were 7 to 12 times higher than mean concentrations found in the other species. Cadmium was found in the tissues of all species; however, levels were consistently highest in equine samples with mean values of 3.09 and 27.7 micrograms/g in liver and kidney, respectively. Copper levels greater than 150 micrograms/g were found predominantly in liver from calves and sheep, with values considerably lower in the remaining species. Mercury levels were low or not detected in all species except horses. Ninety % of equine kidneys and 54% of equine livers had mercury concentrations greater than 0.01 microgram/g, with mean values of 0.18 and 0.06 microgram/g, respectively. Lead was found in tissues of all species; however, values greater than 2 micrograms/g were found only in 2 kidneys from adult cattle and 1 kidney from a horse. Selenium, tested only in cattle, was found at mean concentrations of 0.28 microgram/g in liver, and 0.92 microgram/g in kidney. Relatively high zinc levels were found in livers of horses, pigs, and calves, with respective mean concentrations of 67.3, 65.6, and 70.2 micrograms/g. PMID- 1917806 TI - Liquid chromatographic determination of tolnaftate in commercial products. AB - A liquid chromatographic (LC) method for the determination of the antifungal agent tolnaftate was developed. Isolation of the analyte was achieved by direct extraction or dilution with acetonitrile-water (80 + 20) followed by reverse phase liquid chromatography using a C18 column. The mobile phase was acetonitrile water (80 + 20) acidified with phosphoric acid. Detection was by UV absorption at a wavelength of 257 nm. The proposed procedure was applied to 20 consumer products comprising 6 formulation types, including solutions, powders, liquid and power aerosols, creams, and gels. The precision (RSD) for the products ranged from 0.23 to 1.16% (n = 5), and recoveries via fortification ranged from 98.1 to 103.0%. Six different brands of C18 columns were evaluated for use with the method. The overall simplicity and versatility of the method suggest possible adaptations to both regulatory and quality-control situations. PMID- 1917808 TI - Determination of carbadox-related residues in swine liver by gas chromatography/mass spectrometry with ion trap detection. AB - The ion trap detector (ITD), in combination with a capillary gas chromatograph and under chemical ionization conditions, offers sufficient sensitivity to determine carbadox-related residues as the methyl ester derivative of quinoxaline 2-carboxylic acid at 3 micrograms/kg or higher in porcine liver. A tetradeuterated internal standard of QME effectively compensates for losses incurred during sample preparation. The method produced mean levels of 3.3 (+/- 0.5), 5.5 (+/- 0.8), and 10.1 (+/- 0.9) micrograms/kg for liver fortified at 3, 5, and 10 micrograms/kg. When applied to analysis of samples containing incurred residues of 14C-carbadox at the low microgram/kg level, results were comparable to those obtained by reverse isotope dilution analysis. PMID- 1917807 TI - Determination of oxolinic acid residues in salmon muscle tissue by liquid chromatography with fluorescence detection. AB - The present paper describes a method for determination of oxolinic acid in salmon muscle tissue. Tissue (0.5-2 g) mixed with 2 g anhydrous sodium sulfate is extracted twice with ethyl acetate, centrifuged, and the extract evaporated. The residue is partitioned in a mixture of hexane and 0.01M oxalic acid and the aqueous phase chromatographed using fluorescence detection at 327 nm excitation and 369 nm emission. Calibration and standard curves are linear from 10-200 ppb and 100-2000 ppb at different sensitivity settings. Recoveries ranged from 71-83% in spiked blanks, with a CV of 4-10.3% over a 2-week period. Preliminary results in treated salmon were variable, possibly because some fish refused to eat medicated feed. PMID- 1917810 TI - Dry rehydratable film for enumeration of total coliforms and Escherichia coli in foods: collaborative study. AB - Rehydratable dry-film plating methods for total coliforms and Escherichia coli in foods have been compared to the AOAC most probable number methods. Fourteen laboratories participated in the collaborative study. Three coliform and E. coli levels in 6 samples of 4 product types (flour, nuts, cheese, and beef with gravy) and in 3 samples of 2 product types (mushrooms and raw turkey) were tested in duplicate by the participants. The mean log counts for the 3 methods were comparable. In general, the repeatability and reproducibility variances of the plating methods were as good as or better than that of the MPN method. The method has been adopted official first action by AOAC. PMID- 1917809 TI - A rapid method for the determination of chlorine, phosphorus, and sulfur in flours of grains and legumes using wavelength dispersive x-ray flourescence spectrometry. AB - A rapid method for the determination of chlorine, phosphorus, and sulfur in commercial flours of wheat, barley, maize, rice, field bean, and soybean by wavelength dispersive x-ray fluorescence spectrometry has been developed. The flours are strained through a 425 microns sieve, then pelletized and measured. The total analysis time for the quantitation of chlorine, phosphorus, and sulfur is less than 20 min per sample. Calibration is carried out using a standard additions method with mixed standards. The method is accurate and precise, and appears to be adequate for routine analyses. PMID- 1917811 TI - Comparison of Preston agar and a blood-free selective medium for detection of Campylobacter jejuni in food. AB - The present collaborative study compares recovery of Campylobacter jejuni from food in 2 agar media. Six laboratories analyzed 8 samples each of chicken liver inoculated with Campylobacter jejuni. Samples were enriched in Preston broth and isolation was carried out on Preston agar (PA) and campylobacter blood-free selective medium (CBFS), a charcoal-based medium with cefoperazone and amphoteracin as antibiotic supplements. There was no difference in the recovery rate between the 2 agar media; however, the specificity of CBFS was better than that of PA. There was a slightly better growth of campylobacters, and competing organisms were more inhibited on CBFS than on PA. PMID- 1917812 TI - Immunochromatography of fusarochromanone mycotoxins. AB - The present paper describes an enzyme-linked immunoassay (ELISA) used in combination with thin-layer chromatography (TLC) and liquid chromatography (LC) for determination of fusarochromanone (TDP) mycotoxins in barley, wheat, and a Fusarium culture grown in rice and corn. The mycotoxins were first extracted from the sample with 100% methanol and subjected to TLC or LC without additional cleanup treatment. Individual fractions eluted from TLC or LC were acetylated, then analyzed by ELISA. Determinations of TDP toxins at levels as low as 0.1 and 0.5 ng were achieved by ELISA in combination with LC and TLC, respectively. The detection limit for TDP-1 in barley and wheat was about 20 ppb by ELISA alone as compared with a detection limit of 5 ppb by a combination of ELISA with either TLC or LC. Overall analytical recovery (% of added) of TDP-1 added to barley and wheat at 5, 10, and 20 ppb of TDP-1 was 106.9 +/- 15.3 and 113.2 +/- 11.6 by LC ELISA and 108.8 +/- 9.1 and 110.4 +/- 4.9 by TLC-ELISA, respectively. Analysis of extracts obtained from Fusarium equiseti R6137 grown in corn and rice by the combination of TLC and ELISA revealed that diacetyl-TDP was also produced by this fungus in addition to TDP-1 and TDP-2. Comparable results were obtained when fungal extracts were subjected to ELISA, LC, and immunochromatography (i.e., combination of ELISA with either TLC or LC). PMID- 1917813 TI - Enhanced supercritical fluid carbon dioxide extraction of pesticides from foods using pelletized diatomaceous earth. AB - Supercritical fluid carbon dioxide (SC-CO2), when used with an extraction enhancer, comprises a supercritical fluid extraction (SFE) system for extraction of pesticides and matrix components from fatty and nonfatty foods. After being mixed with the enhancer, samples ranging from 95% water to pure lipophilic oils can be extracted efficiently with SC-CO2. This extraction technique yields analyte recoveries in excess of 85% for over 30 types of pesticides at incurred levels ranging from 0.005 to 2 ppm in such diverse matrixes as carrots, lettuce, peanut butter, hamburger, and fortified butter fat and fortified potatoes. SC-CO2 provides a solvent medium that is nontoxic, nonflammable, and inexpensive while also eliminating the use and disposal of potentially carcinogenic organic solvents. PMID- 1917814 TI - Multiresidue matrix solid phase dispersion (MSPD) extraction and gas chromatographic screening of nine chlorinated pesticides in catfish (Ictalurus punctatus) muscle tissue. AB - A multiresidue technique for extraction and gas chromatographic screening of 9 insecticide (lindane, heptachlor, aldrin, heptachlor epoxide, p,p'-DDE, dieldrin, endrin, p,p'-TDE, and p,p'-DDT) residues in catfish (Ictalurus punctatus) muscle tissue is presented. The 9 insecticides, plus dibutyl chlorendate internal standard, were fortified into catfish muscle tissue (0.5 g) and blended with 2 g C18 (octadecylsilyl derivatized silica reverse-phase material). The C18/muscle tissue matrix blend was fashioned into a column by adding the blend to a 10 mL syringe barrel containing 2 g activated Florisil. The insecticides were then eluted from the column with acetonitrile (8 mL), and a portion (2 microL) of the acetonitrile eluate was then directly analyzed by gas chromatography with electron capture detection. Unfortified blank controls were treated similarly. The resultant extracts contained pesticide analytes (31.25-500 ng/g) free of interfering compounds when analyzed. Correlation coefficients for the 9 extracted pesticide standard curves (linear regression analysis, n = 5) ranged from 0.9967 (+/- 0.0018) to 0.9999 (+/- 0.0001). Average percentage recoveries (82 +/- 4.8% to 97 +/- 3.6%, n = 25 for each insecticide), interassay (5.0 +/- 2.7% to 16.9 +/ 6.5%, n = 25 for each insecticide) and intraassay (1.8 to 4.7%, n = 5 for each insecticide) variabilities were indicative of an acceptable methodology for the analysis and screening of these residues in catfish muscle tissue. PMID- 1917815 TI - Rapid pentachlorophenol evaluation in solid matrixes by second derivative UV spectroscopy for application to wood and leather samples. AB - A method for the quail-quantitative evaluation of pentachlorophenol (PCP) in solid matrixes has been developed. The procedure is based on solid-liquid extraction of solid samples (leather or wood), followed by purification on a cyanopropyl column and determination of the preservative by second derivative UV spectroscopy considering the PCP A peak-through value (304-297 nm). The method allows rapid PCP determination in the concentration range 1-40 micrograms/mL; any matrix interference is avoided by the purification step and recoveries of the preservative were 99.12% (RSD% 0.13) for the leather matrix and 98.03 (RSD% 0.17) for the wood matrix. PMID- 1917816 TI - Modified gas chromatographic/mass spectrometric method for determination of daminozide in high protein food products. AB - A modified version of the Conditt and Baumgardner gas chromatographic/mass spectroscopic (GC/MS) method for determination of daminozide in peanut butter and raw peanuts is described. Daminozide in the food product is hydrolyzed to unsymmetrical dimethylhydrazine (UDMH) by sodium hydroxide digestion. The generated UDMH is distilled from the food matrix and captured by reaction with salicylaldehyde in a condensation trap. Resulting high pH distillates generated by peanuts and peanut products are adjusted back to a pH of 5-6 through addition of glacial acetic acid. After thermal incubation and extraction into methylene chloride, salicylaldehyde dimethylhydrazone is separated from interferences by capillary GC and quantitated by MS using the selective ion monitoring (SIM) mode. Quantitation of daminozide is based on the ratio of the salicylaldehyde dimethylhydrazone molecular ion (m/z 164) to the molecular ion (m/z 153) of the internal standard, 4-nitroanisole. Confirmation of daminozide identity is determined by relative intensity of the m/z 164 ion to the m/z 120 (C7H4ON) ion. Improved m/z 164 ion intensity and reduction of neighboring interferences due to acetic acid treatment permitted a daminozide detection limit of 0.005 ppm in a 50 g sample and an associated 0.02 ppm limit of quantitation. This modification is specific for high protein samples that generate high pH distillates such as peanuts and peanut products and is not specifically intended for analysis of low protein samples. PMID- 1917817 TI - Quantitative determination of amines in wine by liquid chromatography. AB - A liquid chromatographic (LC) procedure is described for the determination by dansylation of the following 16 kinds of biogenic amines found in wine: monomethylamine (MM), ethylamine (EM), iso- and n-propylamine (Pr), iso- and n butylamine (Bu), iso- and n-amylamine (Am), pyrrolidine (PY), 2-phenethylamine (PH), tryptamine (TR), putrescine (PU), cadaverine (CA), histamine (HI), tyramine (TY), and spermidine (SP). The amines in white and red wine were applied to a column of Amberlite CG-50 type I resin (Na-form) after the column had been washed with water and eluted with 1N hydrochloric acid. This eluate was evaporated to dryness under reduced pressure and derivatized with dansyl chloride (DNS). LC separations were performed on Finepak SIL C18S and LiChrosorb RP-8 columns with an acetonitrile-water elution gradient. In the survey of commercial wines by this method, most of the samples were found to contain 12 amines, including iso-Am, CA, PU, TY, and others. The highest levels of these amines were 4.84 micrograms PU/mL in red wine, and 5.11 micrograms iso-Am/mL in white wine. The total levels of amines in red wine were comparatively higher than in white wine. PMID- 1917819 TI - Symposium on microbiology update: old friends and new enemies. Listeria monocytogenes. AB - Listeria monocytogenes, one of the "new enemies" in food microbiology, is a human and animal pathogen that is widespread in nature. The organism is a transient constituent of the intestinal flora excreted by 1-10% of healthy humans. It is an extremely hardy organism and can survive for many years in the cold in naturally infected sources. L. monocytogenes has been isolated from a wide variety of foods, including dairy products, meats, and fish. Although most of the foodborne listeriosis outbreaks have been linked to the consumption of dairy products, recent sporadic cases have been associated with meats, as well as other foods. It is now recognized that listeriolysin 0, a 60-kilodalton protein, is one of the major virulence factors of the organism. All strains of L. monocytogenes are pathogenic by definition although some appear to be more virulent than others. There have been recent reports of hemolytic isolates of L. monocytogenes, which are nonpathogenic for mice. Attachment to and penetration of cells also appear to be prerequisites for human infection. Cultural methodology for isolating the organism from foods has been in a state of flux since 1985. Rapid methods using both ELISA and DNA technology have been developed. Because of the widespread nature of the organism, it is nearly impossible to eliminate it from the food supply. However, by using a hazard analysis-critical control point approach, the health hazard associated with this organism can be reduced to a minimum. PMID- 1917818 TI - A qualitative colorimetric test for brominated vegetable oil in soft drinks. AB - A simple and precise method of detecting brominated vegetable oil (BVO) in soft drinks is described. After extraction of BVO using diethyl ether, the concentrated ethereal solution was treated with a small quantity of zinc dust to convert the organic bromide to inorganic form; the solution was subsequently treated with lead dioxide to liberate bromine. The bromine evolved was detected by means of fluorescein-impregnated filter paper strip that turns pink because eosin is formed. The test can detect as low as 10 ppm (2 mg/200 ml) of BVO under experimental conditions. Gas chromatography was carried out on sodium methoxide derivatives prepared from ether extract for quantitation. PMID- 1917820 TI - Symposium on microbiology update: old friends and new enemies. Bacillus cereus. AB - Bacillus cereus is an environmentally ubiquitous, Gram-positive, spore-forming bacillus responsible for 2 distinct foodborne disease syndromes as well as other manifestations of pathogenicity. The rapid-onset, "emetic," foodborne-disease syndrome is associated with an emetic toxin; the delayed-onset, "diarrheal" syndrome is associated with elaboration of enterotoxin. The majority of methods for detection of these toxins have relied on in vivo testing. More recent work on purification of enterotoxin facilitated the development of a rapid, specific, fluorescent immunodot assay and a tissue culture screening assay for enterotoxin. Work on characterization and detection of emetic toxin is ongoing. PMID- 1917821 TI - Symposium on microbiology update: old friends and new enemies. Staphylococcus aureus. AB - The analytical methods for the detection of the staphylococcal enterotoxins can be divided into 2 categories: (1) methods for detection of enterotoxin-producing staphylococcal strains; (2) methods for detection of enterotoxin in foods. Gel diffusion methods (Ouchterlony, microslide), in which the enterotoxin produced by any given strain is compared to one of the identified enterotoxins, are used most frequently for strain testing. The sensitivity of these methods is from 0.1 to 0.5 micrograms enterotoxin/mL, which is normally adequate to determine the enterotoxigenicity of strains. The methods for the detection of enterotoxin in foods need to be much more sensitive to detect less than 1 ng of enterotoxin/g of food that may be present. The radioimmunoassay (RIA), the enzyme-linked immunosorbent assay (ELISA), and the reversed passive latex agglutination (RPLA) method have the necessary sensitivity to detect 1 ng/g of enterotoxin in foods without the use of complicated extraction-concentration procedures. Kits based on the ELISA and RPLA methods are now available commercially for the detection of enterotoxins in foods. Tests have shown that the ELISA methods are somewhat more sensitive than the RPLA method. PMID- 1917823 TI - Producing holograms, Part 2: Making transmission and reflection holograms. PMID- 1917822 TI - Symposium on microbiology update: old friends and new enemies. Clostridium perfringens. AB - In the United States and Canada, Clostridium perfringens remains a leading cause of bacterial food poisoning in humans. It has been primarily associated with meat and poultry products prepared in food service establishments. Fecal spore levels of 10(6) or more per g are considered indicative of a food poisoning outbreak. However, elevated spore levels of this organism are frequently seen in healthy elderly individuals, an observation that complicates investigations of suspected outbreaks. Recent studies with this population indicate that fecal enterotoxin levels are a valuable and effective assay for confirming outbreaks due to this organism. With regard to the toxin itself, a membrane protein of 50 000-70,000 molecular weight has been isolated as a possible enterotoxin-receptor site. It is the subsequent action of the toxin on membrane structure that results in the loss of ions and fluid associated with illness. In addition, the enterotoxin gene has been cloned in E. coli and sequenced. Using toxin-specific DNA probes, only 6% of non-symptomatic farm animals were found to possess the enterotoxin gene, disproving the hypothesis that all strains of this organism can produce the toxin. PMID- 1917824 TI - Graphic design for desktop publishing, Part 1: Typography. PMID- 1917825 TI - A primer on digital imaging--post production for still photography: Part 2. PMID- 1917826 TI - Application of ultraviolet fluorescence microscopy to the morphological classification of ticks. PMID- 1917827 TI - "Giraffe fetus". PMID- 1917828 TI - Photographic measurement of skin movement. PMID- 1917829 TI - Dimethyl sulfoxide reductase of Escherichia coli: an investigation of function and assembly by use of in vivo complementation. AB - Dimethyl sulfoxide (DMSO) reductase of Escherichia coli is a membrane-bound, terminal anaerobic electron transfer enzyme composed of three nonidentical subunits. The DmsAB subunits are hydrophilic and are localized on the cytoplasmic side of the plasma membrane. DmsC is the membrane-intrinsic polypeptide, proposed to anchor the extrinsic subunits. We have constructed a number of strains lacking portions of the chromosomal dmsABC operon. These mutant strains failed to grow anaerobically on glycerol minimal medium with DMSO as the sole terminal oxidant but exhibited normal growth with nitrate, fumarate, and trimethylamine N-oxide, indicating that DMSO reductase is solely responsible for growth on DMSO. In vivo complementation of the mutant with plasmids carrying various dms genes, singly or in combination, revealed that the expression of all three subunits is essential to restore anaerobic growth. Expression of the DmsAB subunits without DmsC results in accumulation of the catalytically active dimer in the cytoplasm. The dimer is thermolabile and catalyzes the reduction of various substrates in the presence of artificial electron donors. Dimethylnaphthoquinol (an analog of the physiological electron donor menaquinone) was oxidized only by the holoenzyme. These results suggest that the membrane-intrinsic subunit is necessary for anchoring, stability, and electron transport. The C-terminal region of DmsB appears to interact with the anchor peptide and facilitates the membrane assembly of the catalytic dimer. PMID- 1917830 TI - The tdh and serA operons of Escherichia coli: mutational analysis of the regulatory elements of leucine-responsive genes. AB - The tdh promoter of Escherichia coli is induced seven- to eightfold when cells are grown in the presence of exogenous leucine. A scheme was devised to select mutants that exhibited high constitutive expression of the tdh promoter. The mutations in these strains were shown to lie within a previously identified gene (lrp) that encodes Lrp (leucine-responsive regulatory protein). By deletion analysis, the site of action of Lrp was localized to a 25-bp region between coordinates -69 and -44 of the tdh promoter. Disruption of a 12-bp presumptive target sequence found in this region of tdh resulted in constitutively derepressed expression from the tdh promoter. Similar DNA segments (consensus, TTTATTCtNaAT) were also identified in a number of other promoters, including each of the Lrp-regulated promoters whose nucleotide sequence is known. The sequence of the promoter region of serA, an Lrp-regulated gene, was determined. No Lrp consensus target sequence was present upstream of serA, suggesting that Lrp acts indirectly on the serA promoter. A previously described mutation in a leucine responsive trans-acting factor, LivR (J. J. Anderson, S. C. Quay, and D. L. Oxender, J. Bacteriol. 126:80-90, 1976), resulted in constitutively repressed expression from the tdh promoter and constitutively induced expression from the serA promoter. The possibility that LivR and Lrp are allelic is discussed. PMID- 1917831 TI - Gel electrophoretic analysis of Zymomonas mobilis glycolytic and fermentative enzymes: identification of alcohol dehydrogenase II as a stress protein. AB - The 13 major enzymes which compose the glycolytic and fermentative pathways in Zymomonas mobilis are particularly abundant and represent one-half of the soluble protein in exponential-phase cells. One- and two-dimensional polyacrylamide gel electrophoresis maps were developed for 12 of these enzymes. Assignments were made by comigration with purified proteins, comparison with overexpressed genes in recombinant strains, and Western blots (immunoblots). Although most glycolytic enzymes appeared resistant to turnover and accumulated in stationary-phase cells, the protein levels of pyruvate kinase, alcohol dehydrogenase I, and glucokinase declined. Alcohol dehydrogenase II was identified as a major stress protein and was induced both by exposure to ethanol and by elevated temperature (45 degrees C). This enzyme, encoded by the adhB gene, is expressed from tandem promoters which share partial sequence identity with the Escherichia coli consensus sequence for heat shock proteins. PMID- 1917832 TI - Interaction of selenoprotein PA and the thioredoxin system, components of the NADPH-dependent reduction of glycine in Eubacterium acidaminophilum and Clostridium litorale [corrected]. AB - Purification of protein PA of the glycine reductase complex from Eubacterium acidaminophilum and Clostridium litorale [corrected] was monitored by a new spectrophotometric assay. The procedure depended on a specific two- to threefold stimulation of a dihydrolipoamide dehydrogenase activity that is elicited by the interaction of a thioredoxin reductase-like flavoprotein and thioredoxin from both organisms. Protein PA isolated from E. acidaminophilum by 75Se labeling and monitoring of the dithioerythritol-dependent glycine reductase activity was identical in its biochemical, structural, and immunological properties to the protein isolated by using the stimulation assay. Proteins PA from both organisms were glycoproteins of Mr about 18,500 and exhibited very similar N-terminal amino acid sequences. Depletion of thioredoxin from crude extracts of E. acidaminophilum totally diminished the NADPH-dependent but not the dithioerythritol-dependent glycine reduction. The former activity could be fully restored by adding thioredoxin. Antibodies raised against the thioredoxin reductase-like flavoprotein or thioredoxin inhibited to a high extent NADPH dependent but not dithioerythritol-dependent glycine reductase activity. These results indicate the involvement of the thioredoxin system in the electron flow from reduced pyridine nucleotides to glycine reductase. PMID- 1917833 TI - The Escherichia coli htrP gene product is essential for bacterial growth at high temperatures: mapping, cloning, sequencing, and transcriptional regulation of htrP. AB - We identified and characterized a new Escherichia coli gene, htrP. The htrP gene was identified because its insertional inactivation by the Tn10 transposon results in the inability of E. coli to form colonies at temperatures above 37 degrees C and a slow growth phenotype at 30 degrees C. The htrP gene was cloned and mapped to 66.3 min on the E. coli genetic map, 4 kbp clockwise from the tolC gene. The htrP gene was sequenced and shown to code for an acidic, 27,471-Da polypeptide and to be transcribed counterclockwise with respect to the genetic map. The predicted HtrP protein has two potential transmembrane segments and shares an identity of 64.4% over a length of 210 amino acids with the LuxH protein. Despite the fact that the htrP gene is essential for E. coli growth exclusively at high temperatures, the levels of htrP-specific transcripts decrease with increasing temperature. PMID- 1917835 TI - Molecular cloning and sequence of the thdF gene, which is involved in thiophene and furan oxidation by Escherichia coli. AB - Our previous work resulted in the isolation of mutant strains of Escherichia coli K-12 which were able to oxidize furans and thiophenes as a result of mutations in several novel genes. Some of the genes involved in thiophene oxidation were cloned into the multicopy vector pUC19. The plasmid pKA10 carries a 3.8-kb chromosomal fragment which encodes a previously undiscovered gene involved in thiophene oxidation. Three proteins with approximate molecular sizes of 48, 30, and 26 kDa were overproduced by cells carrying pKA10. Maxicell experiments and DNA sequence analysis indicated that the 48- and 26-kDa proteins are encoded by pKA10, whereas the 30-kDa protein is apparently chromosomally derived. A cassette specifying kanamycin resistance was inserted into various sites on pKA10. An insertion which abolished the 48-kDa protein also abolished thiophene oxidation. Chromosomal integration of pKA10::Kan allowed us to locate the chromosomal insert of pKA10 at 84 min on the E. coli genetic map by transduction. Since no previously identified genes involved in thiophene metabolism are located in this region, we designated the gene for the 48-kDa protein as thdF. Sequencing of the 3.8-kb insert revealed an overlap of several hundred bases with the regulatory and structural regions of the tnaA gene, which is also located at 84 min. The 26 kDa protein is probably truncated tnaA protein. An open reading frame corresponding to the 48-kDa thdF protein was located next to the tnaA gene, which encodes tryptophanase, but was transcribed in the opposite sense. PMID- 1917836 TI - Purification and characterization of ADP-ribosyltransferases (exoenzyme C3) of Clostridium botulinum type C and D strains. AB - By cation-exchange column chromatography followed by gel filtration or hydroxylapatite column chromatography, ADP-ribosyltransferases (exoenzyme C3) were isolated from culture supernatants of Clostridium botulinum type C strains Stockholm (CST) and 6813 (C6813) and from type D strains South African (DSA) and 1873 (D1873), and their molecular properties were compared. The purified C3 enzymes were homogeneous in polyacrylamide gel electrophoresis. The C3 enzymes existed as single-chain polypeptides with molecular masses of 25.0 to 25.5 kDa and transferred ADP-riboses to the same substrates in rat brain membrane extract. The C3 enzymes could be roughly classified into two groups with respect to amino acid composition, amino-terminal sequence, and antigenicity. One group contains the C3 enzymes of strains C6813 and DSA, and the other contains those of strains CST and D1873. The specific activity of the C3 enzyme of strain C6813 was about 15 times higher than that of the C3 enzyme of strain CST. These results indicate that the classification of the C3 molecules differs from that of the neurotoxin molecules. PMID- 1917834 TI - Physiological studies of tryptophan transport and tryptophanase operon induction in Escherichia coli. AB - Escherichia coli forms three permeases that can transport the amino acid tryptophan: Mtr, AroP, and TnaB. The structural genes for these permeases reside in separate operons that are subject to different mechanisms of regulation. We have exploited the fact that the tryptophanase (tna) operon is induced by tryptophan to infer how tryptophan transport is influenced by the growth medium and by mutations that inactivate each of the permease proteins. In an acid hydrolyzed casein medium, high levels of tryptophan are ordinarily required to obtain maximum tna operon induction. High levels are necessary because much of the added tryptophan is degraded by tryptophanase. An alternate inducer that is poorly cleaved by tryptophanase, 1-methyltryptophan, induces efficiently at low concentrations in both tna+ strains and tna mutants. In an acid-hydrolyzed casein medium, the TnaB permease is most critical for tryptophan uptake; i.e., only mutations in tnaB reduce tryptophanase induction. However, when 1 methyltryptophan replaces tryptophan as the inducer in this medium, mutations in both mtr and tnaB are required to prevent maximum induction. In this medium, AroP does not contribute to tryptophan uptake. However, in a medium lacking phenylalanine and tyrosine the AroP permease is active in tryptophan transport; under these conditions it is necessary to inactivate the three permeases to eliminate tna operon induction. The Mtr permease is principally responsible for transporting indole, the degradation product of tryptophan produced by tryptophanase action. The TnaB permease is essential for growth on tryptophan as the sole carbon source. When cells with high levels of tryptophanase are transferred to tryptophan-free growth medium, the expression of the tryptophan (trp) operon is elevated. This observation suggests that the tryptophanase present in these cells degrades some of the synthesized tryptophan, thereby creating a mild tryptophan deficiency. Our studies assign roles to the three permeases in tryptophan transport under different physiological conditions. PMID- 1917837 TI - Malolactic fermentation: electrogenic malate uptake and malate/lactate antiport generate metabolic energy. AB - The mechanism of metabolic energy production by malolactic fermentation in Lactococcus lactis has been investigated. In the presence of L-malate, a proton motive force composed of a membrane potential and pH gradient is generated which has about the same magnitude as the proton motive force generated by the metabolism of a glycolytic substrate. Malolactic fermentation results in the synthesis of ATP which is inhibited by the ionophore nigericin and the F0F1 ATPase inhibitor N,N-dicyclohexylcarbodiimide. Since substrate-level phosphorylation does not occur during malolactic fermentation, the generation of metabolic energy must originate from the uptake of L-malate and/or excretion of L lactate. The initiation of malolactic fermentation is stimulated by the presence of L-lactate intracellularly, suggesting that L-malate is exchanged for L lactate. Direct evidence for heterologous L-malate/L-lactate (and homologous L malate/L-malate) antiport has been obtained with membrane vesicles of an L. lactis mutant deficient in malolactic enzyme. In membrane vesicles fused with liposomes, L-malate efflux and L-malate/L-lactate antiport are stimulated by a membrane potential (inside negative), indicating that net negative charge is moved to the outside in the efflux and antiport reaction. In membrane vesicles fused with liposomes in which cytochrome c oxidase was incorporated as a proton motive force-generating mechanism, transport of L-malate can be driven by a pH gradient alone, i.e., in the absence of L-lactate as countersubstrate. A membrane potential (inside negative) inhibits uptake of L-malate, indicating that L-malate is transported an an electronegative monoanionic species (or dianionic species together with a proton). The experiments described suggest that the generation of metabolic energy during malolactic fermentation arises from electrogenic malate/lactate antiport and electrogenic malate uptake (in combination with outward diffusion of lactic acid), together with proton consumption as result of decarboxylation of L-malate. The net energy gain would be equivalent to one proton translocated form the inside to the outside per L-malate metabolized. PMID- 1917838 TI - A base pair transition in a DNA sequence with dyad symmetry upstream of the puf promoter affects transcription of the puc operon in Rhodobacter capsulatus. AB - A DNA sequence with dyad symmetry upstream of the transcriptional start of the Rhodobacter capsulatus puf operon, which encodes pigment-binding proteins of the light-harvesting I complex and of the reaction center, has previously been shown to be a protein-binding site (G. Klug, Mol. Gen. Genet. 226:167-176, 1991). When a low-copy-number plasmid with a base pair transition at position -43 within this dyad symmetry in front of the puf structural genes was transferred into a Rhodobacter strain with the puf operon deleted, different phenotypes occurred during cultivation of the transconjugants and the kinetics of the loss of the wild-type phenotype was dependent on the oxygen tension in the culture. After growth for 150 generations, the different phenotypes were stably inherited. The strains having the wild-type phenotype carried the wild-type puf DNA sequence. The original mutation was still present in the strains that showed lighter color. These strains had less light-harvesting II complex in the membrane and showed lower rates of transcription of the puc operon, which encodes the proteins of this complex. This deregulation of puc expression was due to one or more chromosomally located, secondary mutations, not directly to the mutation present on the plasmid. Thus, a single-base-pair transition in the puf upstream region can result in a deregulation of puc expression, suggesting a direct or indirect transcriptional coregulation of both these operons by a common factor. PMID- 1917839 TI - Biosynthesis of vitamin B12: stepwise amidation of carboxyl groups b, d, e, and g of cobyrinic acid a,c-diamide is catalyzed by one enzyme in Pseudomonas denitrificans. AB - The cobalamin biosynthetic pathway enzyme that catalyzes amidation of 5'-deoxy-5' adenosyl-cobyrinic acid a,c-diamide was purified to homogeneity from extracts of a recombinant strain of Pseudomonas denitrificans by a four-column procedure. The purified protein had an isoelectric point of 5.6 and molecular weights of 97,300 as estimated by gel filtration and 57,000 as estimated by gel electrophoresis under denaturing conditions, suggesting that the active enzyme is a homodimer. Stepwise Edman degradation provided the sequence of the first 16 amino acid residues at the N terminus. The enzyme catalyzed the four-step amidation sequence from cobyrinic acid a,c-diamide to cobyric acid via the formation of cobyrinic acid triamide, tetraamide, and pentaamide intermediates. The amidations are carried out in a specific order; this order was not determined. The enzyme was specific to coenzyme forms of substrates and did not carry out amidation of the carboxyl group at position f. The amidation reactions were ATP/Mg2+ dependent and exhibited a broad optimum around pH 7.5. L-Glutamine was shown to be the preferred amide group donor (Km congruent to 45 microM) but could be replaced by ammonia (Km = 20 mM). For all of the four partially amidated substrates, the Km values were in the micromolar range and the Vmax values were about 7,000 nmol h-1 mg-1. PMID- 1917840 TI - Genetic and sequence analyses of a Pseudomonas denitrificans DNA fragment containing two cob genes. AB - A genetic analysis of a 12-kb DNA fragment containing Pseudomonas denitrificans cob genes was performed by transposon-mediated insertional mutagenesis. The nucleotide sequence and genetic analysis have shown that a 4.8-kb DNA subfragment carried two cob genes (cobS and cobT). Biochemical data concerning the complemented cobS and cobT mutants suggested that the cobS product was involved in cobalt insertion-mediating reactions and that the cobT product was involved in the transformation of precorrin-3 into cobyrinic acid. PMID- 1917841 TI - Genetic analysis, nucleotide sequence, and products of two Pseudomonas denitrificans cob genes encoding nicotinate-nucleotide: dimethylbenzimidazole phosphoribosyltransferase and cobalamin (5'-phosphate) synthase. AB - Tn5 Sp(r) transposons have been inserted into the 8-kb Pseudomonas denitrificans DNA fragment from complementation group D, which carries cob genes. Genetic analysis and the nucleotide sequence revealed that only two cob genes (cobU and cobV) were found on this cob genomic locus. Nicotinate-nucleotide: dimethylbenzimidazole phosphoribosyltransferase (EC 2.4.2.21) was assayed and purified to homogeneity from a P. denitrificans strain in which cobU and cobV were amplified. The purified enzyme was identified as the cobU gene product on the basis of identical molecular weights and N-terminal sequences. Cobalamin (5' phosphate) synthase activity was increased when cobV was amplified in P. denitrificans. The partially purified enzyme catalyzed not only the synthesis of cobalamin 5'-phosphate from GDP-cobinamide and alpha-ribazole 5'-phosphate but also the one-step synthesis of cobalamin from GDP-cobinamide and alpha-ribazole. Biochemical data provided evidence that cobV encodes cobalamin (5'-phosphate) synthase. PMID- 1917842 TI - Effect of regB on expression from the P1 and P2 promoters of the Pseudomonas aeruginosa regAB operon. AB - Exotoxin A production in Pseudomonas aeruginosa is dependent on two regulatory genes, regA and regB, which are located in tandem on the chromosome. Expression of regA and regB is controlled by two promoters (P1 and P2) situated upstream of the regAB locus. We have studied the effect of the regA and regB gene products on transcription from the regAB promoters. Transcriptional and translational fusions, under the control of the P. aeruginosa regA promoters, were used to analyze the regulation of these promoters in a variety of genetic backgrounds. When the regA P1 promoter was supplied in trans to strains lacking expression of regB (PAO1) or lacking transcription of the regAB operon (PA103-29), little activity from the P1 promoter was detected. In contrast, activity from the P2 promoter was not affected in either PAO1 or PA103-29. Sequence analysis of the regAB operon of PA103-29 detected two mutations. One of the mutations is predicted to result in a premature stop codon in the regA open reading frame. We complemented PA103-29 with a construction containing regA and an inactive regB or a construction containing both regA and regB to directly analyze the effect of regB on transcription of the regAB operon. When PA103-29 was complemented with regA but not regB, we could not detect any transcription from the P1 promoter. Complementation of PA103-29 with both regA and regB resulted in a high level of transcription from the P1 promoter and a corresponding early transcriptional activation of toxA. Our results indicated that induction of transcription from the P1 promoter requires the regB open reading frame and thus the regAB operon is autogenously regulated in P. aeruginosa. PMID- 1917843 TI - A membrane protein is required for bacteriophage c2 infection of Lactococcus lactis subsp. lactis C2. AB - Phage-resistant mutants, isolated from cultures of Lactococcus lactis subsp. lactis C2 infected with phage c2, did not form plaques but bound phage normally. The mutants were sensitive to another phage, sk1, although the number of plaques was reduced approximately 56% and the plaques were four times smaller. Binding to phage sk1 was reduced about 10%. Another group of phage-resistant mutants, isolated from cultures infected with phage sk1, bound normally to both phages c2 and sk1 but did not form plaques with either phage. Carbohydrate analyses by gas chromatography of the cell walls showed no significant differences in saccharide compositions between the wild-type and phage-resistant cells. However, a difference was observed in the interactions of the phage with the cytoplasmic membranes. Membranes from the wild-type cells, but not mutant cells, inactivated phage c2. Phage sk1 was not inactivated by membrane from either strain. Treatment of wild-type membranes with proteinase K eliminated the ability of the membrane to inactivate the phage, whereas treatment with mutanolysin had no effect. On the basis of this ability to inactivate the phage, a membrane protein was partially purified by gel filtration and ion-exchange chromatography. Under nondenaturing conditions, the phage-inactivating protein has an apparent Mr of approximately 350,000. The protein has an apparent subunit size of 32 kDa, which suggests that it normally exists as a multimer with 10 to 12 subunits or in association with other membrane components. It is proposed that this protein is required for phage c2 infection. PMID- 1917844 TI - Phylogenetic analysis of the spirochetes. AB - The 16S rRNA sequences were determined for species of Spirochaeta, Treponema, Borrelia, Leptospira, Leptonema, and Serpula, using a modified Sanger method of direct RNA sequencing. Analysis of aligned 16S rRNA sequences indicated that the spirochetes form a coherent taxon composed of six major clusters or groups. The first group, termed the treponemes, was divided into two subgroups. The first treponeme subgroup consisted of Treponema pallidum, Treponema phagedenis, Treponema denticola, a thermophilic spirochete strain, and two species of Spirochaeta, Spirochaeta zuelzerae and Spirochaeta stenostrepta, with an average interspecies similarity of 89.9%. The second treponeme subgroup contained Treponema bryantii, Treponema pectinovorum, Treponema saccharophilum, Treponema succinifaciens, and rumen strain CA, with an average interspecies similarity of 86.2%. The average interspecies similarity between the two treponeme subgroups was 84.2%. The division of the treponemes into two subgroups was verified by single-base signature analysis. The second spirochete group contained Spirochaeta aurantia, Spirochaeta halophila, Spirochaeta bajacaliforniensis, Spirochaeta litoralis, and Spirochaeta isovalerica, with an average similarity of 87.4%. The Spirochaeta group was related to the treponeme group, with an average similarity of 81.9%. The third spirochete group contained borrelias, including Borrelia burgdorferi, Borrelia anserina, Borrelia hermsii, and a rabbit tick strain. The borrelias formed a tight phylogenetic cluster, with average similarity of 97%. THe borrelia group shared a common branch with the Spirochaeta group and was closer to this group than to the treponemes. A single spirochete strain isolated fromt the shew constituted the fourth group. The fifth group was composed of strains of Serpula (Treponema) hyodysenteriae and Serpula (Treponema) innocens. The two species of this group were closely related, with a similarity of greater than 99%. Leptonema illini, Leptospira biflexa, and Leptospira interrogans formed the sixth and most deeply branching group. The average similarity within this group was 83.2%. This study represents the first demonstration that pathogenic and saprophytic Leptospira species are phylogenetically related. The division of the spirochetes into six major phylogenetic clusters was defined also by sequence signature elements. These signature analyses supported the conclusion that the spirochetes represent a monophylectic bacterial phylum. PMID- 1917845 TI - Molecular cloning and DNA sequencing of the Escherichia coli K-12 ald gene encoding aldehyde dehydrogenase. AB - The gene ald, encoding aldehyde dehydrogenase, has been cloned from a genomic library of Escherichia coli K-12 constructed with plasmid pBR322 by complementing an aldehyde dehydrogenase-deficient mutant. The ald region was sequenced, and a single open reading frame of 479 codons specifying the subunit of the aldehyde dehydrogenase enzyme complex was identified. Determination of the N-terminal amino acid sequence of the enzyme protein unambiguously established the identity and the start codon of the ald gene. Analysis of the 5'- and 3'-flanking sequences indicated that the ald gene is an operon. The deduced amino acid sequence of the ald gene displayed homology with sequences of several aldehyde dehydrogenases of eukaryotic origin but not with microbial glyceraldehyde-3 phosphate dehydrogenase. PMID- 1917846 TI - Anaerobically expressed Escherichia coli genes identified by operon fusion techniques. AB - Genes that are expressed under anaerobic conditions were identified by operon fusion techniques with a hybrid bacteriophage of lambda and Mu, lambda placMu53, which creates transcriptional fusions to lacZY. Cells were screened for anaerobic expression on XG medium. Nine strains were selected, and the insertion point of the hybrid phage in each strain was mapped on the Escherichia coli chromosome linkage map. The anaerobic and aerobic expression levels of these genes were measured by beta-galactosidase assays in different medium conditions and in the presence of three regulatory mutations (fnr, narL, and rpoN). The anaerobically expressed genes (aeg) located at minute 99 (aeg-99) and 75 (aeg-75) appeared to be partially regulated by fnr, and aeg-93 is tightly regulated by fnr. aeg-60 requires a functional rpoN gene for its anaerobic expression. aeg-46.5 is repressed by narL. aeg-65A and aeg-65C are partially controlled by fnr but only in media containing nitrate or fumarate. aeg-47.5 and aeg-48.5 were found to be anaerobically induced only in rich media. The effects of a narL mutation on aeg 46.5 expression were observed in all medium conditions regardless of the presence or absence of nitrate. This suggests that narL has a regulatory function in the absence of exogenously added nitrate. PMID- 1917847 TI - Analysis of the active center of Bacillus stearothermophilus neopullulanase. AB - The active center of the neopullulanase from Bacillus stearothermophilus was analyzed by means of site-directed mutagenesis. The amino acid residues located in the active center of the neopullulanase were tentatively identified according to a molecular model of Taka-amylase A and homology analysis of the amino acid sequences of neopullulanse, Taka-amylase A, and other amylolytic enzymes. When amino acid residues Glu and Asp, corresponding to the putative catalytic sites, were replaced by the oppositely charged (His) or noncharged (Gln or Asn) amino acid residue, neopullulanase activities toward alpha-(1----4)- and alpha-(1----6) glucosidic linkages disappeared. When the amino acids corresponding to the putative substrate-binding sites were replaced, the specificities of the mutated neopullulanases toward alpha-(1----4)- and alpha-(1----6)-glucosidic linkages were obviously different from that of the wild-type enzyme. This finding proves that one active center of neopullulanase participated in the dual activity toward alpha-(1----4)- and alpha-(1----6)-glucosidic linkages. Pullulan is a linear glucan of maltotriosyl units linked through alpha-(1----6)-glucosidic linkages. The production ratio of panose from pullulan was significantly increased by using the mutated neopullulanase which exhibited higher specificity toward the alpha-(1 ---4)-glucosidic linkage. In contrast, the production ratio of panose was obviously decreased by using the mutated neopullulanse which exhibited higher specificity toward the alpha-(1----6)-glucosidic linkage. PMID- 1917848 TI - Detection of elastase production in Escherichia coli with the elastase structural gene from several non-elastase-producing strains of Pseudomonas aeruginosa. AB - The elastase structural gene from Pseudomonas aeruginosa IFO 3455 has been cloned and sequenced. Using this gene as a probe, we cloned the DNA fragments (pEL3080R, pEL10, and pEL103R) of the elastase gene from non-elastase-producing strains (P. aeruginosa IFO 3080, N-10, and PA103 respectively). These three Pseudomonas strains showed no detectable levels of elastase antigenicity by Western blotting (immunoblotting) or by elastase activity. When elastase structural genes about 8 kb in length were cloned into pUC18, an Escherichia coli expression vector, we were able to detect both elastase antigenicity and elastolytic activity in two bacterial clones (E. coli pEL10 and E. coli pEL103R). However, neither elastolytic activity nor elastase antigenicity was detected in the E. coli pEL3080R clone, although elastase mRNA was observed. The partial restriction map determined with several restriction enzymes of these three structural genes corresponded to that of P. aeruginosa IFO 3455. We sequenced the three DNA segments of the elastase gene from non-elastase-producing strains and compared the sequences with those from the elastase-producing P. aeruginosa strains IFO 3455 and PAO1. In P. aeruginosa N-10 and PA103, the sequences were almost identical to those from elastase-producing strains, except for several nucleotide differences. These minor differences may reflect a microheterogeneity of the elastase gene. These results suggest that two of the non-elastase-producing strains have the normal elastase structural gene and that elastase production is repressed by regulation of this gene expression in P. aeruginosa. Possible reasons for the lack of expression in these two strains are offered in this paper. In P. aeruginosa IFO 3080, the sequence had a 1-base deletion in the coding region, which should have caused a frameshift variation in the amino acid sequence. At present, we have no explanation for the abnormal posttransciptional behavior of this strain. PMID- 1917849 TI - Glycine 100 in the dinitrogenase reductase of Rhodospirillum rubrum is required for nitrogen fixation but not for ADP-ribosylation. AB - Dinitrogenase reductase (Rr2) is required for reduction of the molybdenum dinitrogenase in the nitrogen fixation reaction and is the target of posttranslational regulation in Rhodospirillum rubrum. This posttranslational regulation involves the ADP-ribosylation of Rr2. To study the structural requirements for these two functions of Rr2, i.e., activity and regulation, two site-directed mutations in nifH, the gene encoding Rr2, were constructed and analyzed. The mutations both affected a region of the protein known to be highly conserved in evolution and to be relevant to both of the above properties. These mutants were both Nif-, but one of the altered Rr2s was a substrate for ADP ribosylation. This demonstrates that the ability of Rr2 to participate in nitrogen fixation can be separated from its ability to act as a substrate for ADP ribosylation. PMID- 1917850 TI - Selection, expression, and nucleotide sequencing of the glutamate dehydrogenase gene of Peptostreptococcus asaccharolyticus. AB - The gene for the catabolic NAD-linked glutamate dehydrogenase of Peptostreptococcus asaccharolyticus was cloned by selection of Escherichia coli for complementation of a biosynthetic defect. Cloned fragments containing the gene and the P. asaccharolyticus transcription and translation signals are very highly expressed in E. coli. The nucleotide sequence of the cloned gene was determined. It codes for a polypeptide of 421 amino acids, the sequence of which is similar to those of the NADP-accepting glutamate dehydrogenases. The sequence similarity of this protein to the mammalian glutamate dehydrogenases, which accept both NADP and NAD, is greater than its similarity to the bacterial NADP specific dehydrogenases, suggesting that this NAD-specific bacterial glutamate dehydrogenase and the NADP-specific bacterial dehydrogenases diverged separately from the line leading to the dual-specificity mammalian glutamate dehydrogenases. PMID- 1917851 TI - Transcriptional organization of the rfaGBIJ locus of Salmonella typhimurium. AB - The transcriptional organization of the rfaGBIJ gene cluster of Salmonella typhimurium was studied by using lacZ and cat transcriptional probes. The results indicated that the leftward end of the gene cluster (rfaG-rfaB-rfaI) is an operon that is transcribed from one or more promoters that lie upstream of rfaG. The results further indicated that the product of the rfaH (sfrB) gene acts as a positive regulator of transcription of the entire rfaGBIJ cluster. At least one site required for the RfaH-mediated transcriptional regulation lies within or very close to the upstream promoter. PMID- 1917852 TI - Control of glucose metabolism by enzyme IIGlc of the phosphoenolpyruvate dependent phosphotransferase system in Escherichia coli. AB - The quantitative effects of variations in the amount of enzyme IIGlc of the phosphoenolpyruvate:glucose phosphotransferase system (PTS) on glucose metabolism in Escherichia coli were studied. The level of enzyme IIGlc could be adjusted in vivo to between 20 and 600% of the wild-type chromosomal level by using the expression vector pTSG11. On this plasmid, expression of the structural gene for enzyme IIGlc, ptsG, is controlled by the tac promoter. As expected, the control coefficient (i.e., the relative increase in pathway flux, divided by the relative increase in amount of enzyme) of enzyme IIGlc decreased in magnitude if a more extensive pathway was considered. Thus, at the wild-type level of enzyme IIGlc activity, the control coefficient of this enzyme on the growth rate on glucose and on the rate of glucose oxidation was low, while the control coefficient on uptake and phosphorylation of methyl alpha-glucopyranoside (an enzyme IIGlc specific, nonmetabolizable glucose analog) was relatively high (0.55 to 0.65). The implications of our findings for PTS-mediated regulation, i.e., inhibition of growth on non-PTS compounds by glucose, are discussed. PMID- 1917853 TI - Indirect stimulation of recombination in Escherichia coli K-12: dependence on recJ, uvrA, and uvrD. AB - Direct and indirect UV-stimulated homologous genetic recombination was investigated in Escherichia coli strains blocked in several host-encoded functions. Genetic recombination was assayed by measuring beta-galactosidase produced after recombination between two noncomplementing lacZ ochre alleles. Both types of stimulation (direct and indirect) were found to be primarily RecF pathway-mediated. In a rec+ background, both direct and indirect stimulation were found to be dependent on uvrD (coding for helicase II). In a recB21 sbcB15 background, direct and indirect stimulation were uvrD dependent only when the strain was additionally deficient in the UvrABC excision repair pathway. Indirect but not direct stimulation was also dependent on recJ (coding for a 5'-to-3' exonuclease specific for single-stranded DNA) regardless of sbcA or sbcB configuration. The methyl-directed mismatch repair system (mutSLH) also appeared to play an important role in stimulation. On the basis of these findings, we suggest that excision of UV-induced DNA damage is a prelude to UV-mediated stimulation of genetic recombination. PMID- 1917854 TI - Electrogenic L-malate transport by Lactobacillus plantarum: a basis for energy derivation from malolactic fermentation. AB - L-Malate transport in Lactobacillus plantarum was inducible, and the pH optimum was 4.5. Malate uptake could be driven by an artificial proton gradient (delta pH) or an electroneutral lactate efflux. Because L-lactate efflux was unable to drive L-malate transport in the absence of a delta pH, it did not appear that the carrier was a malate-lactate exchanger. The kinetics of malate transport were, however, biphasic, suggesting that the external malate concentration was also serving as a driving force for low-affinity malate uptake. Because the electrical potential (delta psi, inside negative) inhibited malate transport, it appeared that the malate transport-lactate efflux couple was electrogenic (net negative) at high concentrations of malate. De-energized cells that were provided with malate only generated a large proton motive force (greater than 100 mV) when the malate concentration was greater than 5 mM, and malate only caused an increase in cell yield (glucose-limited chemostats) when malate accumulated in the culture vessel. The use of the malate gradient to drive malate transport (facilitated diffusion) explains how L. plantarum derives energy from malolactic fermentation, a process which does not involve substrate-level phosphorylation. PMID- 1917855 TI - Localization of the lysine epsilon-aminotransferase (lat) and delta-(L-alpha aminoadipyl)-L-cysteinyl-D-valine synthetase (pcbAB) genes from Streptomyces clavuligerus and production of lysine epsilon-aminotransferase activity in Escherichia coli. AB - Lysine epsilon-aminotransferase (LAT) in the beta-lactam-producing actinomycetes is considered to be the first step in the antibiotic biosynthetic pathway. Cloning of restriction fragments from Streptomyces clavuligerus, a beta-lactam producer, into Streptomyces lividans, a nonproducer that lacks LAT activity, led to the production of LAT in the host. DNA sequencing of restriction fragments containing the putative lat gene revealed a single open reading frame encoding a polypeptide with an approximately Mr 49,000. Expression of this coding sequence in Escherichia coli led to the production of LAT activity. Hence, LAT activity in S. clavuligerus is derived from a single polypeptide. A second open reading frame began immediately downstream from lat. Comparison of this partial sequence with the sequences of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D valine (ACV) synthetases from Penicillium chrysogenum and Cephalosporium acremonium and with nonribosomal peptide synthetases (gramicidin S and tyrocidine synthetases) found similarities among the open reading frames. Since mapping of the putative N and C termini of S. clavuligerus pcbAB suggests that the coding region occupies approximately 12 kbp and codes for a polypeptide related in size to the fungal ACV synthetases, the molecular characterization of the beta-lactam biosynthetic cluster between pcbC and cefE (approximately 25 kbp) is nearly complete. PMID- 1917856 TI - The Escherichia coli ts8 mutation is an allele of fda, the gene encoding fructose 1,6-diphosphate aldolase. AB - The ts8 mutant of Escherichia coli has previously been shown to preferentially inhibit stable RNA synthesis when shifted to the nonpermissive temperature. We demonstrate in this report that the ts8 mutation is an allele of fda, the gene that encodes the glycolytic enzyme fructose-1,6-diphosphate aldolase. We show that ts8 and a second fda mutation, h8, isolated and characterized by A. Bock and F. C. Neidhardt, are dominant mutations and that they encode a thermolabile aldolase activity. PMID- 1917857 TI - A gene encoding lysine 6-aminotransferase, which forms the beta-lactam precursor alpha-aminoadipic acid, is located in the cluster of cephamycin biosynthetic genes in Nocardia lactamdurans. AB - A gene (lat) encoding lysine 6-aminotransferase was found upstream of the pcbAB (encoding alpha-aminoadipylcysteinyl-valine synthetase) and pcbC (encoding isopenicillin N synthase) genes in the cluster of early cephamycin biosynthetic genes in Nocardia lactamdurans. The lat gene was separated by a small intergenic region of 64 bp from the 5' end of the pcbAB gene. The lat gene contained an open reading frame of 1,353 nucleotides (71.4% G + C) encoding a protein of 450 amino acids with a deduced molecular mass of 48,811 Da. Expression of DNA fragments carrying the lat gene in Streptomyces lividans led to a high lysine 6 aminotransferase activity which was absent from untransformed S. lividans. The enzyme was partially purified from S. lividans(pULBS8) and showed a molecular mass of 52,800 Da as calculated by Sephadex gel filtration and polyacrylamide gel electrophoresis. DNA sequences which hybridized strongly with the lat gene of N. lactamdurans were found in four cephamycin-producing Streptomyces species but not in four other actinomycetes which are not known to produce beta-lactams, suggesting that the gene is specific for beta-lactam biosynthesis and is not involved in general lysine catabolism. The protein encoded by the lat gene showed similarity to ornithine-5-aminotransferases and N-acetylornithine-5 aminotransferases and contained a pyridoxal phosphate-binding consensus amino acid sequence around Lys-300 of the protein. The evolutionary implications of the lat gene as a true beta-lactam biosynthetic gene are discussed. PMID- 1917858 TI - Structural and functional relationships between Pasteurella multocida and enterobacterial adenylate cyclases. AB - The Pasteurella multocida adenylate cyclase gene has been cloned and expressed in Escherichia coli. The primary structure of the protein (838 amino acids) deduced from the corresponding nucleotide sequence was compared with that of E. coli. The two enzymes have similar molecular sizes and, based on sequence conservation at the protein level, are likely to be organized in two functional domains: the amino-terminal catalytic domain and the carboxy-terminal regulatory domain. It was shown that P. multocida adenylate cyclase synthesizes increased levels of cyclic AMP in E. coli strains deficient in the catabolite gene activator protein compared with wild-type strains. This increase does not occur in strains deficient in both the catabolite gene activator protein and enzyme III-glucose, indicating that a protein similar to E. coli enzyme III-glucose is involved in the regulation of P. multocida adenylate cyclase. It also indicates that the underlying process leading to enterobacterial adenylate cyclase activation has been conserved through evolution. PMID- 1917859 TI - Condensation of the forespore nucleoid early in sporulation of Bacillus species. AB - Fluorescence microscopic examination coupled with digital videoimage analysis of 4',6-diamidino-2-phenylindole-stained sporulating cells of Bacillus megaterium or Bacillus subtilis revealed a striking condensation of the forespore nucleoid. While both mother cell and forespore compartments had equal amounts of DNA, the forespore nucleoid became greater than 2-fold more condensed than the mother cell nucleoid. The condensation of the forespore nucleoid began after only the first hour of sporulation, 2 to 3 h before expression of most forespore-specific genes including those for small, acid-soluble spore proteins, and was abolished in spo0 mutants but not in spoII or spoIII mutants. It is possible that this striking condensation of forespore DNA plays some role in modulating gene expression during sporulation. PMID- 1917860 TI - Proteus mirabilis mutants defective in swarmer cell differentiation and multicellular behavior. AB - Proteus mirabilis is a dimorphic bacterium which exists in liquid cultures as a 1.5- to 2.0-microns motile swimmer cell possessing 6 to 10 peritrichous flagella. When swimmer cells are placed on a surface, they differentiate by a combination of events that ultimately produce a swarmer cell. Unlike the swimmer cell, the polyploid swarmer cell is 60 to 80 microns long and possesses hundreds to thousands of surface-induced flagella. These features, combined with multicellular behavior, allow the swarmer cells to move over a surface in a process called swarming. Transposon Tn5 was used to produce P. mirabilis mutants defective in wild-type swarming motility. Two general classes of mutants were found to be defective in swarming. The first class was composed of null mutants that were completely devoid of swarming motility. The majority of nonswarming mutations were the result of defects in the synthesis of flagella or in the ability to rotate the flagella. The remaining nonswarming mutants produced flagella but were defective in surface-induced elongation. Strains in the second general class of mutants, which made up more than 65% of all defects in swarming were motile but were defective in the control and coordination of multicellular swarming. Analysis of consolidation zones produced by such crippled mutants suggested that this pleiotropic phenotype was caused by a defect in the regulation of multicellular behavior. A possible mechanism controlling the cyclic process of differentiation and dediferentiation involved in the swarming behavior of P. mirabilis is discussed. PMID- 1917861 TI - Genes coding for integration host factor are conserved in gram-negative bacteria. AB - A genetic system for the selection of clones coding for integration host factor and HU homologs is described. We demonstrate that the himA and hip genes of Serratia marcescens and Aeromonas proteolytica can substitute for the Escherichia coli genes in a variety of biological assays. We find that the sequence and genetic organization of the himA and hip genes of S. marcescens are highly conserved. PMID- 1917863 TI - Occurrence of 2-keto-3-deoxy-D-manno-octonic acid in lipopolysaccharides isolated from Vibrio parahaemolyticus. AB - The occurrence of 2-keto-3-deoxy-D-manno-octonic acid (KDO) in lipopolysaccharides (LPS) of Vibrio parahaemolyticus was demonstrated for the first time by gas chromatography-mass spectrometry after dephosphorylation, reduction, and methylation. KDO was virtually completely phosphorylated, since no KDO was detected by either gas chromatography or thiobarbituric acid assay before dephosphorylation. The level of KDO in all six strains of V. parahaemolyticus investigated ranged from 0.37 to 0.69%, which was considerably lower than that in enterobacterial LPS. PMID- 1917862 TI - Purification and partial characterization of Cob(I)alamin adenosyltransferase from Pseudomonas denitrificans. AB - Cob(I)alamin adenosyltransferase (EC 2.5.1.17) was purified to homogeneity from extracts of a Pseudomonas denitrificans recombinant strain and sequenced at its N terminus. It is a homodimer (each unit with an Mr of 28,000) encoded by cobO. The enzyme adenosylated all of the corrinoids isolated from this microorganism but did not adenosylate cobyrinic acid. PMID- 1917864 TI - Evidence for the establishment of aphid-eubacterium endosymbiosis in an ancestor of four aphid families. AB - Aphids (superfamily Aphidoidea) contain eubacterial endosymbionts localized within specialized cells (mycetocytes). The endosymbionts are essential for the survival of the aphid hosts. Sequence analyses of the 16S rRNAs from endosymbionts of 11 aphid species from seven tribes and four families have indicated that the endosymbionts are monophyletic. Furthermore, phylogenetic relationships within the symbiont clade parallel the relationships of the corresponding aphid hosts. Our findings suggest that this endocytobiotic association was established in a common ancestor of the four aphid families with subsequent diversification into the present species of aphids and their endosymbionts. PMID- 1917865 TI - Participation of ABF-1 protein in expression of the Saccharomyces cerevisiae CAR1 gene. AB - DNA fragments previously shown to be required for expression of the CAR1 (arginase) gene in Saccharomyces cerevisiae and to support transcriptional activation of a reporter gene in a heterologous expression vector were shown to bind purified regulatory protein ABF-1. Two ABF-1 sites were identified in the CAR1 upstream region, one to which ABF-1 protein bound with high affinity and a second to which it bound much less avidly. The higher-affinity ABF-1 binding site upstream of CAR1 was an effective competitor of the HMRE, ARS1 B domain, and COR2 GFI binding sequences for protein binding. Point mutations in the CAR1 high affinity ABF-1 binding site resulted in a 12-fold loss of transcriptional activation of a reporter gene compared with the wild-type CAR1 DNA fragment. These data are consistent with the suggestion that ABF-1 protein is one of the transcription factors involved in expression of the CAR1 gene. PMID- 1917866 TI - Specific DNA binding of the TraM protein to the oriT region of plasmid R100. AB - The product of the traM gene of plasmid R100 was purified as the TraM-collagen beta-galactosidase fusion protein (TraM*) by using a beta-galactosidase-specific affinity column, and the TraM portion of TraM* (TraM') was separated by collagenolysis. Both the TraM* and TraM' proteins were found to bind specifically to a broad region preceding the traM gene. This region (designated sbm) was located within the nonconserved region in oriT among conjugative plasmids related to R100. The region seems to contain four core binding sites (designated sbmA, sbmB, sbmC, and sbmD), each consisting of a similar number of nucleotides and including a homologous 15-bp sequence. This result, together with the observation that the TraM* protein was located in the membrane fraction, indicates the possibility that the TraM protein has a function in anchoring the oriT region of R100 at the sbm sites to the membrane pore, through which the single-stranded DNA is transferred to the recipient. sbmC and sbmD, each of which contained a characteristic inverted repeat sequence, overlapped with the promoter region for the traM gene. This suggests that the expression of the traM gene may be regulated by its own product. PMID- 1917868 TI - Carbon metabolism regulates expression of the pfl (pyruvate formate-lyase) gene in Escherichia coli. AB - The anaerobic expression of pfl is reduced both in a strain mutated in the pgi gene and in a pfkA pfkB double mutant strain when cells are grown in medium supplemented with glucose. When cells are grown in medium supplemented with either fructose or pyruvate, no reduction is observed in these strains. The amount of pyruvate in the cells may be responsible for the reduced expression of pfl in the strains mutated in the genes encoding the glycolytic enzymes. Because of the lowered oxygen concentration in the medium, the expression of pfl is induced when an exponentially growing culture enters the stationary phase. This induction is increased when the Casamino Acid concentration is raised 10-fold or when the medium is supplemented with NaCl. Superhelicity of DNA is decreased in a pgi mutant strain grown in medium supplemented with glucose. The superhelicity is also changed, but the opposite way, in a wild-type strain grown in medium supplemented with Casamino Acids at a high concentration or 0.3 M sodium chloride. Our data show that changes in superhelicity do not affect the aerobic expression of pfl but might be important for the anaerobic induction of pfl. PMID- 1917867 TI - Cloning and expression of a novel protease gene encoding an extracellular neutral protease from Bacillus subtilis. AB - We have cloned from Bacillus subtilis a novel protease gene (nprB) encoding a neutral protease by using a shotgun cloning approach. The gene product was determined to have a molecular mass of 60 kDa. It has a typical signal peptide like sequence at the N-terminal region. The expression of nprB can be stimulated by using a B. subtilis strain, WB30, carrying a sacU(h)h mutation. Expression of this protease gene results in production of a 37-kDa protease in the culture medium. The first five amino acid residues from the N terminus of the mature protease were determined to be Ala-Ala-Gly-Thr-Gly. This indicates that the protease is synthesized in a preproenzyme form. The purified protease has a pH optimum of around 6.6, and its activity can be inhibited by EDTA, 1,10 phenanthroline (a zinc-specific chelator), and dithiothreitol. It retained 65% of its activity after treatment at 65 degrees C for 20 min. Sequence comparison indicates that the mature form of this protease has 66% homology with the two thermostable neutral proteases from B. thermoproteolyticus and B. stearothermophilus. It also shares 65, 61, and 56% homology with the thermolabile neutral proteases from B. cereus, B. amyloliquefaciens, and B. subtilis, respectively. The zinc-binding site and the catalytic residues are all conserved among these proteases. Sequence homology extends into the "propeptide" region. The nprB gene was mapped between metC and glyB and was not required for growth or sporulation. PMID- 1917869 TI - Coordinate regulation of phosphatidylserine decarboxylase in Saccharomyces cerevisiae. AB - Regulation of the activity of the mitochondrial enzyme phosphatidylserine decarboxylase (PSD) was measured in vitro by using membrane preparations from wild-type and mutant strains of Saccharomyces cerevisiae. PSD specific activity was not affected by carbon source, and on all carbon sources, the highest specific activity was observed in cells entering the stationary phase of growth. However, PSD activity was found to be regulated in response to soluble precursors of phospholipid biosynthesis. PSD specific activity was reduced to about 63% of the level observed in unsupplemented wild-type cells when the cells were grown in the presence of 75 microM inositol. The presence of 1 mM choline alone had no repressing effect, but the presence of 1 mM choline and 75 microM inositol together led to further repression to a level of about 28% of the derepressed activity. Regulatory mutations known to affect regulation or expression of genes encoding phospholipid-synthesizing enzymes also affected PSD specific activity. opi1 mutants, which are constitutive for a number of phospholipid-biosynthetic enzymes, were found to have high, constitutive levels of PSD. Likewise, in ino2 or ino4 regulatory mutants, PSD activity was found to be at the fully repressed level regardless of growth condition. Regulation of PSD activity was also affected in several structural-gene mutants under conditions of impaired phosphatidylcholine biosynthesis. Together, these data strongly suggest that PSD expression is controlled by the mechanism of general control of phospholipid biosynthesis that regulates many enzymes of phospholipid biosynthesis. PMID- 1917871 TI - The absence of branched-chain amino acid and growth rate control at the internal ilvEp promoter of the ilvGMEDA operon. AB - The question of whether the promoter ilvEp, located in the coding region of ilvM, the second structural gene in the ilvGMEDA operon, is subject to either amino acid- or growth rate-mediated regulation is examined. The experiments described here were performed with ilvEp-cat and ilvEp-lac fusions carried as single copies on the chromosome. The activity of the ilvEp promoter was found to respond neither to the availability of branched-chain amino acids nor to a wide range of growth rates between 35 to 390 min. In the absence of any known role for the products of the ilvGMEDA operon when repressing levels of branched-chain amino acids are present, there appears to be only a gratuitous role for the transcription at ilvEp. PMID- 1917870 TI - Bacteriophage P1 gene 10 encodes a trans-activating factor required for late gene expression. AB - Amber mutants of bacteriophage P1 were used to identify functions involved in late regulation of the P1 lytic growth cycle. A single function has been genetically identified to be involved in activation of the phage-specific late promoter sequence Ps. In vivo, P1 gene 10 amber mutants fail to trans activate a lacZ operon fusion under the transcriptional control of promoter Ps. Several P1 segments, mapping around position 95 on the P1 chromosome, were cloned into multicopy plasmid vectors. Some of the cloned DNA segments had a deleterious effect on host cells unless they were propagated in a P1 lysogenic background. By deletion and sequence analysis, the harmful effect could be delimited to a 869-bp P1 fragment, containing a 453-bp open reading frame. This open reading frame was shown to be gene 10 by sequencing the amber mutation am10.1 and by marker rescue experiments with a number of other gene 10 amber mutants. Gene 10 codes for an 18.1-kDa protein showing an unusually high density of charged amino acid residues. No significant homology to sequences present in the EMBL/GenBank data base was found, and the protein contained none of the currently known DNA-binding motifs. An in vivo trans activation assay system, consisting of gene 10 under the transcriptional control of an inducible promoter and a gene S/lacZ fusion transcribed from Ps, was used to show that gene 10 is the only phage-encoded function required for late promoter activation. PMID- 1917872 TI - Bacteriophage P1 Bof protein is an indirect positive effector of transcription of the phage bac-1 ban gene in some circumstances and a direct negative effector in other circumstances. AB - Previous genetic studies have suggested that the Bof protein of bacteriophage P1 can act as both a negative and a positive regulator of phage gene expression: in bof-1 prophages, the ref gene and a putative phage ssb gene are derepressed, but expression of an operator-semiconstitutive variant of the phage ban gene (bac-1) is markedly reduced. An explanation of this apparent duality is suggested by recent reports that Bof is a corepressor of genes that are regulated by the phage C1 repressor, including the autoregulated c1 gene itself. Here we show, by means of operon fusions to lacZ, that the balance points between Bof-mediated decreases in c1 expression and Bof-mediated increases in C1 efficacy are different among various C1-regulated genes. Thus, expression of Bof by P1 prophages affects some genes (e.g., bac-1 ban) positively, and others (e.g., ref) negatively. Even at bac-1 ban, where the positive indirect effect of Bof is physiologically dominant, Bof can be seen to act as a corepressor if C1 is supplied from a nonautoregulated (ptac-c1) source, eliminating the effect of Bof on C1 synthesis. PMID- 1917873 TI - Overproduction and localization of components of the polyketide synthase of Streptomyces glaucescens involved in the production of the antibiotic tetracenomycin C. AB - Three proteins, including the beta-keto acyl synthase and the acyl carrier protein, involved in the synthesis of the polyketide antibiotic tetracenomycin C by Streptomyces glaucescens GLA.0 were produced in Escherichia coli by using the T7 RNA polymerase-dependent pT7-7 expression vector. Changing the N-terminal codon usage of two of the genes greatly increased the level of protein produced without affecting mRNA levels, suggesting improvements in translational efficiency. Western immunoblot analysis of cytoplasmic and membrane fractions of S. glaucescens with antibodies raised to synthetic oligopeptides corresponding to the two presumed components of the beta-keto acyl synthase indicated that both proteins were membrane bound; one appears to be proteolytically cleaved before or during association with the membrane. The beta-keto acyl synthase could be detected in stationary-phase cultures but not in rapidly growing cultures, correlating with the time of appearance of tetracenomycin C in the medium. PMID- 1917875 TI - Genes 1.2 and 10 of bacteriophages T3 and T7 determine the permeability lesions observed in infected cells of Escherichia coli expressing the F plasmid gene pifA. AB - Infections of F plasmid-containing strains of Escherichia coli by bacteriophage T7 result in membrane damage that allows nucleotides to exude from the infected cell into the culture medium. Only pifA of the F pif operon is necessary for "leakiness" of the T7-infected cell. Expression of either T7 gene 1.2 or gene 10 is sufficient to cause leakiness, since infections by phage containing null mutations in both of these genes do not result in permeability changes of the F containing cell. Even in the absence of phage infection, expression from plasmids of either gene 1.2 or 10 can cause permeability changes, particularly of F plasmid-containing cells. In contrast, gene 1.2 of the related bacteriophage T3 prevents leakiness of the infected cell. In the absence of T3 gene 1.2 function, expression of gene 10 causes membrane damage that allows nucleotides to leak from the cell. Genes 1.2 and 10 of both T3 and T7 are the two genes involved in determining resistance or sensitivity to F exclusion; F exclusion and leakiness of the phage-infected cell are therefore closely related phenomena. However, since leakiness of the infected cell does not necessarily result in phage exclusion, it cannot be used as a predictor of an abortive infection. PMID- 1917874 TI - Regulation of the SOS response in Bacillus subtilis: evidence for a LexA repressor homolog. AB - The inducible SOS response for DNA repair and mutagenesis in the bacterium Bacillus subtilis resembles the extensively characterized SOS system of Escherichia coli. In this report, we demonstrate that the cellular repressor of the E. coli SOS system, the LexA protein, is specifically cleaved in B. subtilis following exposure of the cells to DNA-damaging treatments that induce the SOS response. The in vivo cleavage of LexA is dependent upon the functions of the E. coli RecA protein homolog in B. subtilis (B. subtilis RecA) and results in the same two cleavage fragments as produced in E. coli cells following the induction of the SOS response. We also show that a mutant form of the E. coli RecA protein (RecA430) can partially substitute for the nonfunctional cellular RecA protein in the B. subtilis recA4 mutant, in a manner consistent with its known activities and deficiencies in E. coli. RecA430 protein, which has impaired repressor cleaving (LexA, UmuD, and bacteriophage lambda cI) functions in E.coli, partially restores genetic exchange to B. subtilis recA4 strains but, unlike wild-type E. coli RecA protein, is not capable of inducing SOS functions (expression of DNA damage-inducible [din::Tn917-lacZ] operons or RecA synthesis) in B. subtilis in response to DNA-damaging agents or those functions that normally accompany the development of physiological competence. Our results provide support for the existence of a cellular repressor in B. subtilis that is functionally homologous to the E. coli LexA repressor and suggest that the mechanism by which B. subtilis RecA protein (like RecA of E. coli) becomes activated to promote the induction of the SOS response is also conserved. PMID- 1917876 TI - Components of ice nucleation structures of bacteria. AB - Nonprotein components attached to the known protein product of the inaZ gene of Pseudomonas syringae have been identified and shown to be necessary for the most efficient ice nucleation of supercooled H2O. Previous studies have shown that cultures of Ina+ bacteria have cells with three major classes of ice-nucleating structures with readily differentiated activities. Further, some cells in the culture have nucleating activities intermediate between those of the different classes and presumably have structures that are biosynthetic intermediates between those of the different classes. Since these structures cannot be readily isolated and analyzed, their components have been identified by the use of specific enzymes or chemical probes, by direct incorporation of labeled precursors, and by stimulation of the formation of specific classes of freezing structures by selective additions to the growth medium. From these preliminary studies it appears that the most active ice nucleation structure (class A) contains the ice nucleation protein linked to phosphatidylinositol and mannose, probably as a complex mannan, and possibly glucosamine. These nonprotein components are characteristic of those used to anchor external proteins to cell membranes of eucaryotic cells and suggest that a similar but not identical anchoring mechanism is required for efficient ice nucleation structure. The class B structure has been found to contain protein presumably linked to the mannan and glucosamine moieties but definitely not to the phosphatidylinositol. The class C structure, which has the poorest ice nucleation activity, appears to be the ice nucleation protein linked to a few mannose residues and to be partially imbedded in the outer cell membrane. PMID- 1917877 TI - Formation of bacterial membrane ice-nucleating lipoglycoprotein complexes. AB - The preliminary finding that nonprotein additions to the protein product of the ice-nucleating gene of Pseudomonas syringae or Erwinia herbicola are essential for ice nucleation at the warmest temperatures has led to experiments aimed at identifying possible linkages between the ice protein and the other components. It appears that the protein is coupled to various sugars through N- and O-glycan linkages. Mannose residues are apparently bound via an N-glycan bond to the amide nitrogen of one or more of the three essential asparagine residues in the unique amino-terminal portion of the protein. In turn, these mannose residues are involved in the subsequent attachment of phosphatidylinositol to the nucleation structure. This phosphatidylinositol-mannose-protein structure is the critical element in the class A nucleating structure. In addition to sugars attached to the asparagine residues, additional sugar residues appear to be attached by O glycan linkages to serine and threonine residues in the primary repeating octapeptide, which makes up 70% of the total ice protein. These additional sugar residues include galactose and glucosamine and most likely additional mannose residues. These conclusions were based on (i) the changes in ice-nucleating activity due to the action of N- and O-glycanases, alpha- and beta-mannosidoses, and beta-galactosidase; (ii) immunoblot analyses of ice proteins in cell extracts after enzyme treatments; and (iii) the properties of transformed Ice+ Escherichia coli cells containing plasmids with defined amino-terminal and carboxyl-terminal deletions in the ice gene. Finally, evidence is presented that these sugar residues may play a role in aggregating the ice gene lipoglycoprotein compound into larger aggregates, which are the most effective ice nucleation structures. PMID- 1917878 TI - Erwinia carotovora subsp. carotovora extracellular protease: characterization and nucleotide sequence of the gene. AB - The prt1 gene encoding extracellular protease from Erwinia carotovora subsp. carotovora EC14 in cosmid pCA7 was subcloned to create plasmid pSK1. The partial nucleotide sequence of the insert in pSK1 (1,878 bp) revealed a 1,041-bp open reading frame (ORF1) that correlated with protease activity in deletion mutants. ORF1 encodes a polypeptide of 347 amino acids with a calculated molecular mass of 38,826 Da. Escherichia coli transformed with pSK1 or pSK23, a subclone of pSK1, produces a protease (Prt1) intracellularly with a molecular mass of 38 kDa and a pI of 4.8. Prt1 activity was inhibited by phenanthroline, suggesting that it is a metalloprotease. The prt1 promoter was localized between 173 and 1,173 bp upstream of ORF1 by constructing transcriptional lacZ fusions. Primer extension identified the prt1 transcription start site 205 bp upstream of ORF1. The deduced amino acid sequence of ORF1 showed significant sequence identity to metalloproteases from Bacillus thermoproteolyticus (thermolysin), B. subtilis (neutral protease), Legionella pneumophila (metalloprotease), and Pseudomonas aeruginosa (elastase). It has less sequence similarity to metalloproteases from Serratia marcescens and Erwinia chrysanthemi. Locations for three zinc ligands and the active site for E. carotovora subsp. carotovora protease were predicted from thermolysin. PMID- 1917879 TI - Optical sectioning of microbial biofilms. AB - Scanning confocal laser microscopy (SCLM) was used to visualize fully hydrated microbial biofilms. The improved rejection of out-of-focus haze and the increased resolution of SCLM made it preferable to conventional phase microscopy for the analysis of living biofilms. The extent of image improvement was dependent on the characteristics of individual biofilms and was most apparent when films were dispersed in three dimensions, when they were thick, and when they contained a high number of cells. SCLM optical sections were amenable to quantitative computer-enhanced microscopy analyses, with minimal interference originating from overlying or underlying cell material. By using SCLM in conjunction with viable negative fluorescence staining techniques, horizontal (xy) and sagittal (xz) sections of intact biofilms of Pseudomonas aeruginosa, Pseudomonas fluorescens, and Vibrio parahaemolyticus were obtained. These optical sections were then analyzed by image-processing techniques to assess the distribution of cellular and noncellular areas within the biofilm matrices. The Pseudomonas biofilms were most cell dense at their attachment surfaces and became increasingly diffuse near their outer regions, whereas the Vibrio biofilms exhibited the opposite trend. Biofilms consisting of different species exhibited distinctive arrangements of the major biofilm structural components (cellular and extracellular materials and space). In general, biofilms were found to be highly hydrated, open structures composed of 73 to 98% extracellular materials and space. The use of xz sectioning revealed more detail of biofilm structure, including the presence of large void spaces within the Vibrio biofilms. In addition, three-dimensional reconstructions of biofilms were constructed and were displayed as stereo pairs. Application of the concepts of architectural analysis to mixed- or pure-species biofilms will allow detailed examination of the relationships among biofilm structure, adaptation, and response to stress. PMID- 1917880 TI - Variations of Candida albicans electrophoretic karyotypes. AB - We previously described 14 rare spontaneous morphological mutants of Candida albicans that were associated with chromosomal aberrations (E. P. Rustchenko Bulgac, F. Sherman, and J. B. Hicks, J. Bacteriol. 172:1276-1283, 1990). Improved conditions for separation of chromosomes, as well as hybridization probes, were used to investigate the variation of karyotypes of clinical isolates and additional morphological mutants. All 23 newly analyzed morphological mutants, representing frequently occurring and highly unstable colonial forms, had a variety of altered karyotypes. All chromosomal changes were similar to those previously observed in mutants m1 to m14. In this study, I particularly noted that the most frequent changes involved the long chromosome VIII, which carries ribosomal DNA cistrons. Two rates of instability were uncovered by analyzing the progenies from two highly unstable mutants. An unstable mutant proved to be able to continuously produce a large number of altered karyotypes that could result in a wide variety of different phenotypes. Furthermore, all four independent clinical isolates, FC18, C9, 3153A, and WO-1, common laboratory strains, revealed different electrophoretic karyotypes and distinct colonial morphologies on a synthetic medium, similar to spontaneous mutants. The differences of electrophoretic karyotypes observed among clinical isolates resembled the changes found among different kinds of spontaneous morphological mutants. These findings contribute to the understanding of natural karyotypic variability and are in agreement with the hypothesis that chromosomal alterations observed spontaneously under laboratory conditions provide this amictic species with genetic variability in nature. PMID- 1917881 TI - Synthesis of thiamine in Salmonella typhimurium independent of the purF function. AB - In Salmonella typhimurium, the first five steps in purine biosynthesis also serve as the first steps in the biosynthesis of the pyrimidine moiety of thiamine (vitamin B1). Strains with null mutations of the first gene of purine-thiamine synthesis (purF) can, under some circumstances, grow without thiamine. This suggests the existence of an alternative pathway to thiamine that can function without the purF protein. To demonstrate the nature and map position of the purF mutations corrected, a fine-structure genetic map of the purF gene was made. The map allows identification of deletion mutations that remove virtually all of the purF gene, as defined by mutations. We describe conditions and mutations (panR) which allow B1 synthesis appears to require enzymes which act mutants lacking purF function. The alternative route of B1 synthesis appears to require enzymes which act subsequent to the purF enzyme in the purine pathway. PMID- 1917882 TI - Determination of the nick site at oriT of IncI1 plasmid R64: global similarity of oriT structures of IncI1 and IncP plasmids. AB - The nick site at the origin of transfer, oriT, of IncI1 plasmid R64 was determined. A site-specific and strand-specific cleavage of the phosphodiester bond was introduced during relaxation of the oriT plasmid DNA. Cleavage occurred between 2'-deoxyguanosine and thymidine residues, within the 44-bp oriT core sequence. The nick site was located 8 bp from the 17-bp repeat. A protein appeared to be associated with the cleaved DNA strand at the oriT site following relaxation. This protein was observed to bind to the 5' end of the cleaved strand, since the 5'-phosphate of the cleaved strand was resistant to the phosphate exchange reaction by polynucleotide kinase. In contrast, the 3' end of the cleaved strand appeared free, since it was susceptible to primer extension by DNA polymerase I. The global similarity of the oriT structures of IncI1 and IncP plasmids is discussed. PMID- 1917883 TI - Structural and germination defects of Bacillus subtilis spores with altered contents of a spore coat protein. AB - The start sites for transcription and translation of a Bacillus subtilis spore coat protein gene, cotT, were determined. The CotT protein was synthesized as a 10.1-kDa precursor which was processed to a coat polypeptide of 7.8 kDa. Insertional inactivation of the cotT gene resulted in spores with an altered appearance of the inner coat layers and slow germination in response to a germination solution containing fructose, glucose, and asparagine. Rates of germination in L-alanine and in Penassay broth were the same as that of the wild type. A strain containing the cotT gene on a low-copy-number plasmid produced spores with an excess of CotT precursor and a thickening of the striated inner coat. These spores responded poorly to all of the germinants mentioned above. A site-directed mutation of the codon at the processing site of CotT resulted in the accumulation of the precursor in sporulating cells and on the spores, but there was no effect on the germination rates or solvent resistance of these spores. Both the lack and the overproduction of CotT led to subtle alterations in the structure of the inner spore coat and in the capacity of spores to respond to particular germinants. PMID- 1917884 TI - Lethal and mutagenic action of hydrogen peroxide on Haemophilus influenzae. AB - The lethal and mutagenic effects of H2O2 on wild-type Haemophilus influenzae Rd and on uvr1, uvr2, rec1, and rec2 mutant strains were studied. The first two mutants are sensitive to UV, and the second two are defective in recombination. Rd, urv1, and rec1 strains were more sensitive to the killing effect of H2O2 treatment than were uvr2 and rec2 strains. There were peaks of mutagenesis at two H2O2 concentrations over a range of 30 to 275 mM. Our results suggest a specific repair of H2O2 damage that is independent of the Uvr2 and Rec2 gene products. Sensitivity to the killing effect of H2O2 and to the lethal action of near-UV light were similar for Rd and uvr1 strains. This finding suggests that the mechanisms of killing by and repair of H2O2 damage may have some overlap with those of near-UV radiation. PMID- 1917885 TI - Independence of bacteriophage N15 lytic and linear plasmid replication from the heat shock proteins DnaJ, DnaK, and GrpE. AB - The chromosome of the temperate bacteriophage N15 replicates as a linear plasmid with covalently closed ends (or hairpins) when it forms a lysogen. I found that, in contrast to the cases for lambda and the low-copy-number plasmids F and P1, both phage and plasmid replication of N15 are independent of the heat shock proteins DnaJ, DnaK, and GrpE. PMID- 1917887 TI - Primary structures of cytotoxic factors isolated from habu (Trimeresurus flavoviridis) venom. AB - The amino acid sequence of a cytotoxic factor, CTF-I, isolated from the venom of the Japanese habu snake (Trimeresurus flavoviridis) has been determined through automatic phenylisothiocyanate degradation of the PE-protein and derived proteolytic peptides. CTF-I consists of 72 amino acids and contains an Arg-Gly Asp sequence present in trigramin-like peptides isolated from other snake venoms. The primary structure of another cytotoxic factor, CTF-II, consisting of 75 amino acids, was deduced to comprise that of CTF-1 with an additional Glu-Leu-Leu sequence at its N-terminal. PMID- 1917888 TI - Heat shock gene activation by mutant actin is independent of myofibril degeneration in Drosophila muscle. AB - Artificially mutagenized Drosophila Act88F actin genes with triple and double mutations were expressed in the indirect flight muscles of transgenic flies. The triple mutant actin, GD245T (Gly-36----Glu, Glu-83----Asp, and Gly-245----Asp), induced heat shock protein (hsp) synthesis without affecting flight ability. On the other hand, the double mutation, GD245D (Gly-36----Glu and Glu-83----Asp), disrupted myofibrils but induced little hsp synthesis. These results demonstrate that myofibril degeneration is not the primary cause of the anomalous heat shock gene activation by mutant actins. PMID- 1917886 TI - Partitioning of a mini-F plasmid into anucleate cells of the mukB null mutant. AB - The partition-proficient mini-F plasmid pXX325 was stably maintained in the mukB null mutant, which is defective in chromosome partitioning into the two daughter cells. In the null mutant, the plasmid was partitioned into both nucleate and anucleate daughter cells, independently of host chromosomes. PMID- 1917889 TI - Heterogeneity and tissue-specific expression of eukaryotic transcription factor S II-related protein mRNA. AB - Two new cDNA clones for S-II-related proteins were isolated from a mouse liver cDNA library. Analyses of these clones suggested that S-II proteins are a family of proteins with relatively conserved C-terminal regions but variable N-terminal regions, and that some members of this family are expressed in a tissue-specific manner. PMID- 1917890 TI - Nucleotide sequence of the gene encoding NADH dehydrogenase from an alkalophile, Bacillus sp. strain YN-1. AB - The gene encoding NADH dehydrogenase from an alkalophile, Bacillus sp., was cloned and sequenced. The cloned DNA fragment contained an open reading frame of 1,557 nucleotides which encodes a polypeptide composed of 519 amino acid residues (Mr 55,830). The predicted amino acid sequence was consistent with the partial amino acid sequences including the N-terminal and C-terminal sequences determined in a previous study. Sequence comparison with other flavoenzymes revealed high homology between the present dehydrogenase and Escherichia coli thioredoxin reductase. PMID- 1917891 TI - The N-terminal transactivation domain of rat estrogen receptor is localized in a hydrophobic domain of eighty amino acids. AB - In order to determine the transactivation domain(s) of the rat estrogen receptor (rat ER), we made a number of rat ER deletion mutants and transfected the mutant plasmids into COS7 cells together with an estrogen-responsive reporter plasmid, ERE-tk(197)-CAT, which contained the estrogen response element of Xenopus vitellogenin A2 gene. We have identified and localized the N-terminal transactivation domain of the rat ER to a hydrophobic region extending from Ala 59 to Glu 140. PMID- 1917892 TI - 1H-NMR study of the intramolecular interaction of a substrate analogue covalently attached to aspartic acid-101 in lysozyme. AB - We prepared the lysozyme derivative in which the beta-carboxyl group of Asp101 was modified with alpha-O-methyl N-glycylglucosaminide as an amide by means of the carbodimide reaction (alpha-MGG lysozyme). Since Asp101 residue is located at the edge of the active site cleft, a 1H-NMR study was carried out for this derivative in order to investigate the interaction between the introduced substituent and the active site cleft. It was confirmed that the alpha-MGG moiety sat in the active site cleft in alpha-MGG lysozyme from the reduction of line broadening of the NH-proton of Trp63 located in the active site cleft, the remarkable chemical shift change of the methyl group of the alpha-MGG moiety upon adding a trimer of N-acetyl-D-glucosamine [(NAG)3], and the NOE between the C6 proton resonance of Trp63 and the methyl resonance of the alpha-MGG moiety. Furthermore, alpha-MGG lysozyme had increased thermal stability compared with native lysozyme. Therefore, it was concluded that the alpha-MGG moiety covalently attached to Asp101 interacted with the active site cleft to increase the thermal stability of lysozyme. PMID- 1917893 TI - Replacement of an interdomain residue Val39 of Escherichia coli aspartate aminotransferase affects the catalytic competence without altering the substrate specificity of the enzyme. AB - Three mutant Escherichia coli aspartate aminotransferases in which Val39 was changed to Ala, Leu, and Phe by site-directed mutagenesis were prepared and characterized. Among the three mutant and the wild-type enzymes, the Leu39 enzyme had the lowest Km values for dicarboxylic substrates. The Km values of the Ala39 enzyme for dicarboxylates were essentially the same as those of the wild-type (Val39) enzyme. These two mutant enzymes showed essentially the same kcat values for dicarboxylic substrates as did the wild-type enzyme. On the other hand, incorporation of a bulky side-chain at position 39 (Phe39 enzyme) decreased both the affinity (1/Km) and catalytic ability (kcat) toward dicarboxylic substrates. These results show that the position 39 residue is involved in the modulation of both the binding of dicarboxylic substrates to enzyme and the catalytic ability of the enzyme. Although the replacement of Val39 with other residues altered both the kcat and Km values toward various substrates including dicarboxylic and aromatic amino acids and the corresponding oxo acids, it did not alter the ratio of the kcat/Km value of the enzyme toward a dicarboxylic substrate to that for an aromatic substrate. The affinity for aromatic substrates was not affected by changing the residue at position 39. These data indicate that, although the side chain bulkiness of the residue at position 39 correlates well with the activity toward aromatic substrates in the sequence alignment of several aminotransferases [Seville, M., Vincent M.G., & Hahn, K. (1988) Biochemistry 27, 8344-8349], the residue does not seem to be involved in the recognition of aromatic substrates. PMID- 1917895 TI - Purification and carbohydrate-binding specificities of a blood type B binding lectin from hemolymph of a crab (Charybdis japonica). AB - A blood type B binding lectin (CJA-B) was isolated from the hemolymph of the crab Charybdis japonica by affinity chromatography on Sephadex G-200. The molecular mass of the native lectin was determined to be 300 kDa by gradient polyacrylamide gel electrophoresis under nondenaturing conditions. On SDS-polyacrylamide gel electrophoresis, the lectin gave a single protein band with molecular masses of 19 and 38 kDa in the presence and absence of 2-mercaptoethanol, respectively. CJA B contained mannose, N-acetylglucosamine, xylose, and fucose in the molar ratio of 3.0:1.6:1.2:1.1. The protein required calcium ions for hemagglutinating activity and showed specificities for alpha-galactosyl and alpha-glucosyl residues. Studies on hemagglutination inhibition by Synsorbs, which are synthetic oligosaccharides coupled chemically to crystalline silica, showed that the lectin mainly interacts with Gal alpha 1-3Gal. PMID- 1917894 TI - Cytochrome P-450 human-2 (P-450IIC9) in mephenytoin hydroxylation polymorphism in human livers: differences in substrate and stereoselectivities among microheterogeneous P-450IIC species expressed in yeasts. AB - The cDNA of a P-450 human-2 and the two other closely related cDNAs, MP-8 (two deduced amino acids substituted) and lambda hPA6 (two deduced amino acids deleted) were expressed in Saccharomyces cerevisiae cells, and their catalytic and chemical properties were compared to identify which cDNA encodes a major S mephenytoin 4'-hydroxylase in human livers. In immunoblots, P-450 human-2 cDNA derived protein in yeasts was stained at the position identical with P-450 human 2 purified from liver and a major protein in microsomes of 19 Japanese livers. MP 8- and lambda hPA6-derived proteins were immunostained at positions near, but distinct from P-450 human-2, and were not detected in those 19 livers. All three proteins expressed in yeasts catalyzed hydroxylation of mephenytoin, hexobarbital, benzo[a]pyrene and tolbutamide, although the rates of the hydroxylation of most of the drugs by P-450 human-2 were higher than those of the two others. In addition, these expressed proteins showed clear differences in the hydroxylation of chiral substrates: P-450 human-2 catalyzed the hydroxylation of S-mephenytoin five times faster than that of the R-enantiomer. Similar high enantioselectivities were also observed on the hydroxylation of R- and S hexobarbital. However, MP-8- and lambda hPA6-derived proteins catalyzed hydroxylation of these two drugs with less or almost no stereoselectivity. These results indicate that only a few amino acid alterations cause dramatic changes in both the chemical and catalytic properties of P-450 human-2. PMID- 1917896 TI - Isolation and characterization of major urinary oligosaccharides excreted by a patient with type 3 GM1 gangliosidosis. AB - Two major oligosaccharides were isolated from the urine of a patient with type 3 GM1 gangliosidosis. From structural studies including compositional sugar analysis, fast-atom bombardment mass spectrometry, direct-inlet chemical ionization mass spectrometry, methylation analysis, chromium trioxide oxidation, and proton magnetic resonance spectroscopy, their structures were deduced to be as follows: [formula: see text] Both oligosaccharides have beta-linked galactose at the non-reducing ends. Oligosaccharide 1 is one of the most common urinary oligosaccharides found in type 1 and type 2 GM1 gangliosidosis. Oligosaccharide 2, lacto-N-difucohexaose II, has not been described in the urine of GM1 gangliosidosis patients. Excretion of oligosaccharide 1 in the type 3 patient was much less than that of a type 2 patient. Thin-layer chromatographic analysis revealed that the excretion of oligosaccharides with higher molecular weight than that of oligosaccharide 1 (octasaccharide) in the type 3 patient was much less than that of a type 2 patient, raising the possibility that the mutant beta galactosidase of type 3 GM1 gangliosidosis can still act to some extent on higher molecular weight oligosaccharides containing beta-linked galactose at the non reducing end. PMID- 1917897 TI - Purification and characterization of two types of fumarase from Escherichia coli. AB - Two distinct types of fumarase were purified to homogeneity from aerobically grown Escherichia coli W cells. The amino acid sequences of their NH2-terminals suggest that the two enzymes are the products of the fumA gene (FUMA) and fumC gene (FUMC), respectively. FUMA was separated from FUMC by chromatography on a Q Sepharose column, and was further purified to homogeneity on Alkyl-Superose, Mono Q, and Superose 12 columns. FUMA is a dimer composed of identical subunits (Mr = 60,000). Although the activity of FUMA rapidly decreased during storage, reactivation was attained by anaerobic incubation with Fe2+ and thiols. Studies on the inactivation and reactivation of FUMA suggested that oxidation and the concomitant release of iron inactivated the enzyme in a reversible manner. While the inactivated FUMA was EPR-detectable, through a signal with g perpendicular = 2.02 and g = 2.00, the active enzyme was EPR-silent. These results suggested FUMA is a member of the 4Fe-4S hydratases represented by aconitase. After the separation of FUMC from FUMA, purification of the former enzyme was accomplished by chromatography on Phenyl-Superose and Matrex Gel Red A columns. FUMC was stable, Fe-independent and quite similar to mammalian fumarases in enzymatic properties. PMID- 1917898 TI - The existence of two different forms of apo-electron-transferring flavoprotein. AB - The association process of FAD and apo-electron-transferring flavoprotein (apoETF) from hog kidney was investigated. The reaction schemes which involve the association-dissociation of the protein species could be excluded by the light scattering data, which indicated that the molecular weights of apoETF and holoETF are identical. The binding reaction between FAD and a large excess of apoETF was monophasic and obeyed pseudo-first order kinetics. On the other hand, the reaction between apoETF and a large excess of FAD was biphasic: the fast phase obeyed a pseudo-first order reaction, and the rate of the slow phase was almost independent of FAD concentration. These results suggest the existence of two different forms of apoETF, as represented in the following reaction scheme: [formula: see text] where "F" is FAD, "H" is holoETF, and "A" and "A" are the different forms of apoETF. The kinetic parameters were determined as k-1 = 3.9 x 10(4) M-1.s-1, k-1 approximately 10(-5) s-1, k+2 = 1.0 x 10(-3) s-1, and k-2 = 3.1 x 10(-3) s-1, in 50 mM potassium phosphate buffer, pH 7.6, containing 0.3 mM EDTA, and 5% v/v glycerol, at 7 degrees C. The elution patterns of apoETF on molecular sieve chromatography were very different from that of holoETF although the true molecular weights were identical. This result suggests that the structure of apoETF differs greatly from that of holoETF. PMID- 1917899 TI - Identification of the active site of human renin with use of new fluorogenic peptides. AB - Fluorogenic peptide substrates were synthesized in which amino acid residues corresponded to the C-terminal and the N-terminal sides of the site of human angiotensinogen cleaved by renin. Compared with the synthetic substrates of renin previously reported, these fluorogenic substrates had practical advantages in that their digestion products could be rapidly separated and sensitively detected by high-pressure liquid chromatography with a fluorescence detector. The recombinant human renin and human plasma split Leu-Val, which cleavage site is similar to that in human angiotensinogen. The kinetic parameters of the reaction of renin using these substrates were calculated. There seemed to be at least eight subsites in the active site of recombinant human renin, to judge from the enzyme-substrate binding characteristics. The two histidine residues (S5 and S'3) in the octapeptide His-Pro-Phe-His-Leu-Val-Ile-His were important in the enzyme action. PMID- 1917900 TI - Determination of the native subunit pattern of gizzard tropomyosin using antibodies specific to each subunit. AB - The gizzard tropomyosin molecule is composed of two subunits at 1:1 molar ratio. Possible composites of the tropomyosin molecule are two kinds of homodimer (one for each subunit), a heterodimer of two subunits, or a mixture of heterodimer and homodimer(s). We tried to evaluate the native subunit composition of gizzard tropomyosin by cross-linking experiments and immunological methods using specific antibodies to each subunit. For the cross-linking experiment we used dimethyl suberimidate, an amino group-specific cross-linker, in the presence of dithiothreitol to avoid artificial oxidative intersubunit cross-linking. When gizzard tropomyosin was cross-linked, it generated several products which might correspond to dimers formed by intersubunit cross-linkage. When the reaction was carried out for a long time, non-cross-linked subunits completely disappeared and two or three major cross-linked products arose. All of these cross-linked products were recognized by both of the specific antibodies to each subunit. These results indicated that the predominant part, if not all, of gizzard tropomyosin is present as heterodimer. PMID- 1917901 TI - Characterization and location of the L-proline activating fragment from the multifunctional gramicidin S synthetase 2. AB - Gramicidin S synthetase 2 (GS2) derived from Bacillus brevis is a multifunctional single polypeptide (Mr 280,000) with a 4'-phosphopantetheine residue covalently bound to the enzyme. When GS2 was treated with trypsin or chymotrypsin, fragments with some activity were liberated. The molecular mass of the L-proline activating fragment was 114 kDa on SDS-PAGE. This fragment, when incubated with gramicidin S synthetase 1 (GS1) in the presence of phenylalanine and proline, produced D-Phe-L Pro dipeptide. The fragment accepted D-phenylalanine from GS1 in the absence of L proline. The L-proline activating fragment was shown to lack pantothenic acid by microbiological assay. On the other hand, the L-leucine activating fragment, which was partially purified, contained a large amount of pantothenic acid, although it did not form the D-Phe-L-Pro dipeptide. These results indicate that the L-proline activating site is located near an acceptor site for D phenylalanine on GS2, but that it is not adjacent to a 4'-phosphopantetheine group. The N-terminal sequence (15 amino acid residues) of the L-proline activating fragment obtained by trypsin treatment was identical with that of GS2, indicating that the L-proline activating site is located at the N-terminus of the native synthetase. The N-terminal sequence of GS2 has been matched with the amino acid sequence deduced from the nucleotide sequence 71 bp downstream of the stop codon of the GS1 gene except that the first initiator methionine was not detected. PMID- 1917902 TI - Kinetic and stereochemical characterization of hamster liver 3 alpha hydroxysteroid dehydrogenase and 3 alpha(17 beta)-hydroxysteroid dehydrogenase. AB - The kinetic mechanism of NADP(+)-dependent 3 alpha-hydroxysteroid dehydrogenase and NAD(+)-dependent 3 alpha(17 beta)-hydroxysteroid dehydrogenase, purified from hamster liver cytosol, was studied in both directions. For 3 alpha-hydroxysteroid dehydrogenase, the initial velocity and product inhibition studies indicated that the enzyme reaction sequence is ordered with NADP+ binding to the free enzyme and NADPH being the last product to be released. Inhibition patterns by Cibacron blue and hexestrol, and binding studies of coenzyme and substrate are also consistent with an ordered bi bi mechanism. For 3 alpha(17 beta)-hydroxysteroid dehydrogenase, the steady-state kinetic measurements and substrate binding studies suggest a random binding pattern of the substrates and an ordered release of product; NADH is released last. However, the two enzymes transferred the pro-R hydrogen atom of NAD(P)H to the carbonyl substrate. PMID- 1917903 TI - Comparative base specificity, stability, and lectin activity of two lectins from eggs of Rana catesbeiana and R. japonica and liver ribonuclease from R. catesbeiana. AB - Two lectins with RNase activity obtained from eggs of Rana catesbeiana and R. japonica and RNase obtained from R. catesbeiana liver show 65-83% protein homology. The base specificity of these frog proteins was studied with 8 dinucleoside phosphates as substrates and 8 nucleotides as inhibitors. The base specificities of the B1 and B2 sites of these proteins are U greater than C and G greater than U greater than A, C, respectively. The three frog proteins are more resistant than RNase A to heat treatment, guanidine-HCl and pH-induced denaturation; i.e., they retain their native conformation up to at least 70 degrees C at pH 7.5. Differences in stability and base specificity among RNase A and the three frog proteins are discussed in relation to the primary structures. Although the two lectins agglutinate tumor cells (e.g., Ehrlich, S-180 and AH109A ascites carcinoma cells), the liver RNase has no such activity. Agglutination of AH109A cells by the two lectins is inhibited by nucleotides. Our results indicate that the agglutination sites are not identical with, but are related to, the active sites of the three frog proteins. PMID- 1917904 TI - Intermediate and mechanism of hydroxylation of o-iodophenol by salicylate hydroxylase. AB - Salicylate hydroxylase [EC 1.14.13.1] from Pseudomonas putida catalyzes the hydroxylation of salicylate, and also o-aminophenol, o-nitrophenol, and o halogenophenols, to catechol. The reactions with these o-substituted phenols comprise oxygenative deamination, denitration, and dehalogenation, respectively. The reaction stoichiometry, as to NADH oxidized, oxygen consumed, and catechol formed, is 2 : 1 : 1, respectively. The mechanisms for the deiodination and oxygenation of o-iodophenol were investigated in detail by the use of I(+) trapping reagents such as DL-methionine, 2-chlorodimedone, and L-tyrosine. The addition of the traps did not change the molar ratio of catechol formed to NADH oxidized, nor iodinated traps produced were in the incubation mixture. The results suggest that I+ was not produced on the deiodination in the hydroxylation of o-iodophenol. On the other hand, L-ascorbate, L-epinephrine, and phenylhydrazine increased the molar ratio. o-Phenylenediamine decreased it, being converted to phenazine. This suggests that o-benzoquinone is formed in the oxidation of o-iodophenol as a nascent product. The quinone was detected spectrophotometrically by means of the stopped-flow method. Kinetic analysis of the reactions revealed that o-benzoquinone is reduced nonenzymatically to catechol by a second molecule of NADH. A mechanism of elimination for the ortho substituted groups of substrate phenols by the enzyme is proposed and discussed. PMID- 1917905 TI - Metabolic control of K+ channels: an overview. PMID- 1917906 TI - Control of K+ channels by G proteins. AB - Heterotrimeric G3 proteins are though to couple receptors to ionic channels via cytoplasmic mediators such as cGMP in the case of retinal rods, cAMP in the case of olfactory cells, and the cAMP cascade in the case of cardiac myocytes. G protein-mediated second messenger effects on K+ channels are dealt with elsewhere in this series. Recently, membrane-delimited pathways have been uncovered and an hypothesis proposed in which the alpha subunits of G proteins directly couple receptors to ionic channels, particularly K+ channels. While direct coupling has not been proven, the membrane-delimited nature has been established for specific G proteins and their specific K+ channel effectors. PMID- 1917909 TI - Calcium-activated K+ channels: metabolic regulation. AB - Calcium-activated potassium (KCa) channels are highly modulated by a large spectrum of metabolites. Neurotransmitters, hormones, lipids, and nucleotides are capable of activating and/or inhibiting KCa channels. Studies from the last few years have shown that metabolites modulate the activity of KCa channels via: (1) a change in the affinity of the channel for Ca2+ (K 1/2 is modified), (2) a parallel shift in the voltage axis of the activation curves, or (3) a change in the slope (effective valence) of the voltage dependence curve. The shift of the voltage dependence curve can be a direct consequence of the change in the affinity for Ca2+. Recently, the mechanistic steps involved in the modulation of KCa channels are being uncovered. Some interactions may be direct on KCa channels and others may be mediated via G-proteins, second messengers, or phosphorylation. The information given in this review highlights the possibility that KCa channels can be activated or inhibited by metabolites without a change in the intracellular Ca2+ concentration. PMID- 1917908 TI - Calcium-activated potassium channels: regulation by calcium. AB - A wide variety of calcium-activated K channels has been described and can be conveniently separated into three classes based on differences in single-channel conductance, voltage dependence of channel opening, and sensitivity to blockers. Large-conductance calcium-activated K channels typically require micromolar concentrations of calcium to open, and their sensitivity to calcium increases with membrane depolarization, suggesting that they may be involved in repolarization events. Small-conductance calcium-activated K channels are generally more sensitive to calcium at negative membrane potentials, but their sensitivity to calcium is independent of membrane potential, suggesting that they may be involved in regulating membrane properties near the resting potential. Intermediate-conductance calcium-activated K channels are a loosely defined group, where membership is determined because a channel does not fit in either of the other two groups. Within each broad group, variations in calcium sensitivity and single-channel conductance have been observed, suggesting that there may be families of closely related calcium-activated K channels. Kinetic studies of the gating of calcium-activated potassium channels have revealed some basic features of the mechanisms involved in activation of these channels by calcium, including the number of calcium ions participating in channel opening, the number of major conformations of the channels involved in the gating process, and the number of transition pathways between open and closed states. Methods of analysis have been developed that may allow identification of models that give accurate descriptions of the gating of these channels. Although such kinetic models are likely to be oversimplifications of the behavior of a large macromolecule, these models may provide some insight into the mechanisms that control the gating of the channel, and are subject to falsification by new data. PMID- 1917907 TI - ATP-dependent potassium channels of muscle cells: their properties, regulation, and possible functions. AB - ATP-dependent potassium channels are present at high density in the membranes of heart, skeletal, and smooth muscle and have a low Popen at physiological [ATP]i. The unitary conductance is 15-20 pS at physiological [K+]o, and the channels are highly selective for K+. Certain sulfonylureas are specific blockers, and some K channel openers may also act through these channels. KATP channels are probably regulated through the binding of ATP, which may in turn be regulated through changes in the ADP/ATP ratio or in pHi. There is some evidence for control through G-proteins. The channels have complex kinetics, with multiple open and close states. The main effect of ATP is to increase occupancy of long-lived close states. The channels may have a role in the control of excitability and probably act as a route for K+ loss from muscle during activity. In arterial smooth muscle they may act as targets for vasodilators. PMID- 1917910 TI - Phosphorylation of K+ channels in the squid giant axon. A mechanistic analysis. AB - Protein phosphorylation is an important mechanism in the modulation of voltage dependent ionic channels. In squid giant axons, the potassium delayed rectifier channel is modulated by an ATP-mediated phosphorylation mechanism, producing important changes in amplitude and kinetics of the outward current. The characteristics and biophysical basis for the phosphorylation effects have been extensively studied in this preparation using macroscopic, single-channel and gating current experiments. Phosphorylation produces a shift in the voltage dependence of all voltage-dependent parameters including open probability, slow inactivation, first latency, and gating charge transferred. The locus of the effect seems to be located in a fast 20 pS channel, with characteristics of delayed rectifier, but at least another channel is phosphorylated under our experimental conditions. These results are interpreted quantitatively with a mechanistic model that explains all the data. In this model the shift in voltage dependence is produced by electrostatic interactions between the transferred phosphate and the voltage sensor of the channel. PMID- 1917912 TI - Using mutagenesis to study potassium channel mechanisms. AB - The voltage-activated K+ channels are members of an ion channel family that includes the voltage-activated Na+ and Ca2+ channels. These ion channels mediate the transmembrane ionic currents that are responsible for the electrical signals produced by cells. The recent cloning of numerous voltage-activated K+ channels has made it possible to combine molecular-genetic and biophysical methods to study K+ channel mechanisms. These mutagenesis-function studies are beginning to provide new information about the architecture of K+ channel proteins and how they form a voltage-gated, K(+)-selective pore. PMID- 1917913 TI - Phenylarsine oxide induces the cyclosporin A-sensitive membrane permeability transition in rat liver mitochondria. AB - This paper reports an investigation on the effects of the hydrophobic, bifunctional SH group reagent phenylarsine oxide (PhAsO) on mitochondrial membrane permeability. We show that PhAsO is a potent inducer of the mitochondrial permeability transition in a process which is sensitive to both the oxygen radical scavanger BHT and to cyclosporin A. The PhAsO-induced permeability transition is stimulated by Ca2+ but takes place also in the presence of EGTA in a process that maintains its sensitivity to BHT and cyclosporin A. Our findings suggest that, at variance from other known inducers of the permeability transition, PhAsO reacts directly with functional SH groups that are inaccessible to hydrophilic reagents in the absence of Ca2+. PMID- 1917911 TI - Use of toxins to study potassium channels. AB - Potassium channels comprise groups of diverse proteins which can be distinguished according to each member's biophysical properties. Some types of K+ channels are blocked with high affinity by specific peptidyl toxins. Three toxins, charybdotoxin, iberiotoxin, and noxiustoxin, which display a high degree of homology in their primary amino acid sequences, have been purified to homogeneity from scorpion venom. While charybdotoxin and noxiustoxin are known to inhibit more than one class of channel (i.e., several Ca(2+)-activated and voltage dependent K+ channels), iberiotoxin appears to be a selective blocker of the high conductance, Ca(2+)-activated K+ channel that is present in muscle and neuroendocrine tissue. A distinct class of small-conductance Ca(2+)-activated K+ channel is blocked by two other toxins, apamin and leiurotoxin-1, that share no sequence homology with each other. A family of homologous toxins, the dendrotoxins, have been purified from venom of various related species of snakes. These toxins inhibit several inactivating voltage-dependent K+ channels. Although molecular biology approaches have been employed to identify and characterize several species of voltage-gated K+ channels, toxins directed against a particular channel can still be useful in defining the physiological role of that channel in a particular tissue. In addition, for those K+ channels which are not yet successfully probed by molecular biology techniques, toxins can be used as biochemical tools with which to purify the target protein of interest. PMID- 1917915 TI - Initiation of eukaryotic messenger RNA synthesis. PMID- 1917914 TI - L-glutamine transport in native vesicles isolated from Ehrlich ascites tumor cell membranes. AB - Native vesicles isolated from Ehrlich ascites tumor cells accumulate glutamine by means of Na(+)-dependent transport systems; thiocyanate seems to be the more effective anion. The apparent affinity constant for the process was 0.38 mM. The Arrhenius plot gave an apparent activation energy of 12.3 kJ/mol. The structural analogs of glutamine, acivicin (2.5 mM) and azaserine (2.5 mM), inhibited the net uptake by 67 and 70%, respectively. The sulfhydryl reagents mersalyl, PCMBS, NEM, and DTNB also inhibited net uptake, suggesting that sulfhydryl groups may be involved in the activity of the carrier protein. A strong inhibition was detected when the vesicles were incubated in the presence of alanine, cysteine, or serine; in addition, histidine, but not glutamate or leucine, had a negative effect on glutamine transport. PMID- 1917916 TI - Involvement of protein kinase C in the phosphorylation of rhodopsin. AB - The possibility that protein kinase C is involved in phototransduction by phosphorylating rhodopsin was explored in situ and in vitro. Pretreatment of intact retinas with phorbol myristate acetate markedly increased the light dependent phosphorylation of rhodopsin, with the greatest effects observed at lower light levels. Phorbol myristate acetate treatment did not affect rhodopsin phosphorylation in retinas not exposed to light, suggesting that protein kinase C modulates the phosphorylation state of rhodopsin in a light-dependent manner. Limited proteolysis of rhodopsin phosphorylated in situ indicates that protein kinase C modifies rhodopsin on a domain distinct from that recognized by rhodopsin kinase. In vitro, protein kinase C purified from bovine retinas phosphorylated unbleached and bleached rhodopsin. Our results are consistent with protein kinase C phosphorylating unbleached rhodopsin in response to low light, suggesting that protein kinase C plays a role in light adaptation. PMID- 1917917 TI - Inhibition by brefeldin A of protein secretion from the apical cell surface of Madin-Darby canine kidney cells. AB - The effect of brefeldin A (BFA) on total and polarized protein secretion was examined in MDCK cells. Increasing concentrations of BFA have increasingly inhibitory effects on total protein secretion. The total protein secretion was essentially unaffected by BFA at 0.5 microgram/ml. When the BFA concentration was increased to 10 and 30 micrograms/ml, the total protein secretion was reduced to about 70 and 25%, respectively, of the control level. Consistent with this effect on total protein secretion, the Golgi structure as revealed by C6-NBD-ceramide (a fluorescent ceramide analog) staining was essentially unaltered by 0.5 microgram/ml BFA, while 10 and 30 micrograms/ml BFA significantly dispersed the Golgi apparatus. When the polarity of protein secretion was examined, it was found that the ratio of proteins secreted from the apical to those from the basolateral surface was reduced from 1.5-2.0 to 0.4-0.7 by all three BFA concentrations. Furthermore, several proteins which are preferentially released from the apical surface were found to be released without apparent surface polarity, while several other proteins which were preferentially released from the basolateral surface were unaffected. This study suggests that BFA, at 0.5 microgram/ml, can selectively inhibit protein secretion from the apical surface without affecting total protein secretion. The inhibition of apical secretion results in enhanced protein secretion from the basolateral surface. PMID- 1917918 TI - Evidence for a phosphoryl-enzyme intermediate in phosphate ester hydrolysis by purple acid phosphatase from bovine spleen. AB - The possibility of the existence of a covalent enzyme-phosphoryl intermediate, E PO3, during catalysis of phosphate ester hydrolysis by the purple acid phosphatase (PAP) from bovine spleen has been examined. Transphosphorylation experiments show that up to 22% of the phosphoryl group from p-nitrophenyl phosphate (PNPP) can be transferred to primary alcohols. Burst experiments at high pH (9.1 or 8.1 for reduced or oxidized PAP, respectively), where hydrolysis of a phosphoenzyme intermediate is expected to be rate-limiting, show clear evidence for stoichiometric bursts of p-nitrophenolate from PNPP. The formation of base-stable, acid-sensitive adducts between PAP and the 32PO3 group of [gamma 32P]ATP has been demonstrated. The pH dependence of the kinetics parameters for reduced PAP has been determined over the range pH 3-8; a feature with a pKa of approximately 6.75 that is attributable to the enzyme-substrate complex is observed. Taken together, the present results are consistent with a two-stem pseudo Uni Bi mechanism that utilizes a covalent enzyme-phosphoryl intermediate, possibly a phosphohistidine. PMID- 1917919 TI - Characterization of the gene for a proliferation-related phosphoprotein (oncoprotein 18) expressed in high amounts in acute leukemia. AB - The oncoprotein 18 (Op18) gene encodes a proliferation-related cytosolic phosphoprotein, which is induced in normal lymphocytes following mitogenic stimulation. Studies of the Op18 gene are of particular interest because of the proposed role of Op18 protein in signal transduction and because of its occurrence in markedly increased amounts in acute leukemia cells. We have recently reported the cloning and sequencing of two cDNA clones for Op18 (1 and 1.5 kilobases). Both clones code for the same 149-amino acid polypeptide; however, they differ in their 3'-region as a result of alternative polyadenylation. We report here the sequencing of the Op18 gene and describe its expression in leukemia. The Op18 gene, which is 6.3 kilobases in length, is comprised of five exons and four introns and exhibits features that are common to other genes involved in cellular growth and proliferation. The increase in Op18 polypeptide in leukemia is associated with increased RNA transcription without gene amplification or rearrangement. Treatment of K562 leukemia cell line with hemin that induces terminal differentiation resulted in decreased expression of Op18. Our findings suggest that the high amount of Op18 protein in acute leukemia results from increased expression of a structurally unaltered gene. PMID- 1917920 TI - Probing the role of lysine 116 and lysine 244 in the spinach ferredoxin-NADP+ reductase by site-directed mutagenesis. AB - Two mutants of the spinach ferredoxin-NADP+ reductase (FNR) were constructed, expressed by using a heterologous expression system previously described (Aliverti, A., Jansen, T., Zanetti, G., Ronchi, S., Herrmann, R. G., and Curti, B. (1990) Eur. J. Biochem. 191, 551-555), and purified to homogeneity. The mutant enzymes FNR-Lys116Gln and FNR-Lys244Gln were similar to the wild-type enzyme in the physicochemical properties measured; however, both enzymes showed a lower activity. Steady-state kinetic analyses and NADP+ binding measurements of the mutant proteins have revealed that the Lys116Gln enzyme had a catalytic efficiency (kcat/KmNADPH) 500-fold lower than that of the wild-type enzyme, and its interaction with NADP+ was greatly impaired. The Lys244Gln enzyme instead had almost the same kcat in the ferricyanide reductase reaction as the wild-type enzyme, while higher values of KmNADPH and Kd for NADP+ were observed. Thus, protein engineering has enabled us to define the role of Lys-116 and Lys-244 in ferredoxin-NADP+ reductase; whereas Lys-244 contributes to the stabilization of the Michaelis complex, the Lys-116 side chain plays an important role also in the further steps of the catalytic cycle, because both Km and kcat are highly affected by the mutation. PMID- 1917921 TI - Candidate proteins for conductive chloride transport in porcine ileal brush border membrane. AB - Conductive transport of chloride ion is important in controlling ion and fluid secretion by exocrine tissues. The current study was directed at identifying proteins in the intestinal brush-border membrane that may be involved with conductive chloride transport. Reaction of total brush-border membrane protein with phenyl-isothiocyanate inhibited conductive chloride transport into brush border membrane vesicles. The conductive transport process was protected from this inhibition by including the ligands Cl- and alpha-phenylcinnamate in the reaction mixture. Brush-border membrane protein protected by this procedure and labeled with fluorescein had an apparent molecular mass in the region of 130 and 23 kDa on separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Phosphorylation of brush-border membrane protein with [gamma 32P] ATP and endogenous protein kinase under conditions causing activation of chloride conductance in membrane vesicles caused the transfer of 32P to several proteins, including ones in the same molecular size range (130 and 23 kDa) as those identified by the fluorescein labeling procedure. Conductive chloride transport in porcine intestinal brush-border vesicles may occur via proteins identified by this differential labeling procedure. PMID- 1917922 TI - Interactions of the bovine brain A1-adenosine receptor with recombinant G protein alpha-subunits. Selectivity for rGi alpha-3. AB - The ability of the bovine brain A1-adenosine receptor to discriminate between different G protein subtypes was tested using G protein alpha-subunits synthesized in Escherichia coli (rG alpha-subunits). When combined with a 3-fold molar excess of beta gamma-subunit purified from bovine brain and used at high concentrations, all three subtypes of rGi alpha (rGi alpha-1, rGi alpha-2, and rGi alpha-3) and rGo alpha were capable of reconstituting guanine nucleotide sensitive high-affinity binding of the agonist radioligand (-)-N6-3-[125I] (iodo 4-hydroxyphenylisopropyl) adenosine ([125I]HPIA) to the purified A1-adenosine receptor (Kd approximately 1.2 nM). Titration of the A1-adenosine receptor with increasing amounts of rG alpha revealed a approximately 10-fold higher affinity for rGi alpha-3 compared with rGi alpha-1, rGi alpha-2, and rGo alpha. This selectivity was also observed in the absence of beta gamma. Other alpha-subunits (rGs alpha-s, rGs alpha-L, rGs alpha PT, and rGz alpha) did not promote [125I]HPIA binding to the purified receptor. In N-ethylmaleimide-treated bovine brain membranes, rGi alpha-3 was the only rG alpha-subunit capable of reconstituting high-affinity agonist binding. Similarly, rGi alpha-3 competed potently with rGo alpha for activation by the agonist-liganded A1-adenosine receptor, whereas a approximately 50-fold molar excess of rGo alpha was required to quench the receptor-mediated release of [alpha-32P]GDP from rGi alpha-3. Hence, in spite of the extensive homology between alpha-subunits belonging to the Gi/Go group, the A1-adenosine receptor appears to discriminate between the subtypes. This specificity is likely to govern transmembrane signaling pathways in vivo. PMID- 1917924 TI - The effect of plasma von Willebrand factor on the binding of human factor VIII to thrombin-activated human platelets. AB - The binding of 35S-labeled recombinant human Factor VIII to activated human platelets was studied in the presence and absence of exogenous plasma von Willebrand factor. In the absence of added von Willebrand Factor, platelets bound 210 molecules of Factor VIII/platelet when the unbound Factor VIII concentration was 2.0 nM (Kd = 2.9 nM). As the von Willebrand factor concentration was increased, the number of Factor VIII molecules bound/platelet decreased to 10 molecules of Factor VIII bound/platelet at 24 micrograms/ml of added vWF. Addition of an anti-vWF monoclonal antibody that inhibits the vWF-Factor VIII interaction attenuated the ability of vWF to inhibit binding of Factor VIII to platelets. In contrast, addition of a control anti-vWF antibody that does not block the vWF-Factor VIII interaction did not affect the ability of vWF to inhibit Factor VIII binding to platelets. From the vWF concentration dependence of inhibition of Factor VIII-platelet binding, a dissociation constant for the Factor VIII-vWF interaction was calculated (Kd = 0.44 nM). To further elucidate the role that vWF may play in preventing the interaction of Factor VIII with platelets, the platelet binding properties of a Factor VIII deletion mutant (90 73) which lacks the primary vWF-binding site was studied. The binding of this mutant was unaffected by added exogenous vWF. These observations demonstrate that Factor VIII can interact with platelets in a manner independent of vWF but that excess vWF in plasma can effectively compete with platelets for the binding of Factor VIII. In addition, since cleavage of Factor VIII by thrombin separates a vWF-binding domain from Factor VIIIa, we propose that activation of Factor VIII by thrombin may elicit release of activated Factor VIII from vWF and thereby make it fully available for platelet binding. PMID- 1917923 TI - Post-transcriptional destabilization of estrogen receptor mRNA in MCF-7 cells by 12-O-tetradecanoylphorbol-13-acetate. AB - The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the regulation of the estrogen receptor (ER) was investigated in this study. After treatment with 100 nM TPA the concentration of receptor protein was measured using an enzyme immunoassay. By 24 h the receptor protein declined by about 80% from a level of approximately 236 fmol of ER/mg of protein in control cells to 50 fmol of ER/mg of protein in cells treated with TPA. Similar results were obtained with an estrogen receptor ligand binding assay. After removal of TPA, the level of ER returned to control values. 4-alpha-Phorbol, a compound related to TPA, had no effect on ER. The effects of TPA on ER expression appear to be mediated by activation of protein kinase C as H-7, an inhibitor of protein kinase C, blocks these effects. In addition to the effect on ER protein, TPA treatment also resulted in a decrease in the steady-state level of ER mRNA as determined by a RNase protection assay. The metabolic inhibitor cycloheximide was unable to prevent the TPA-induced decrease in ER mRNA. Transcription run-off experiments demonstrated that TPA had no effect on ER gene transcription. A half-life study demonstrated that TPA decreased ER mRNA half-life by a factor of 6 from approximately 4 h in control cells to 40 min in TPA-treated cells. These data suggest that the decline in ER expression is mediated by post-transcriptional destabilization of ER mRNA. PMID- 1917925 TI - An NMR characterization of the regA protein-binding site of bacteriophage T4 gene 44 mRNA. AB - The conformations of two RNA dodecamers that differ markedly in affinity for the regA protein from bacteriophage T4 have been examined by NMR to see if the ability of that protein to discriminate between mRNAs is based on pre-existing differences in their three-dimensional structures. One of the RNAs examined has the same sequence as the site where regA protein binds when it inhibits the expression of gene 44's mRNA. The second RNA differs from the first in having a U instead of a G at position -9; it binds regA protein 100 times less tightly. The NMR data indicate that both RNAs have similar single-stranded conformations and that they each resemble an isolated strand of a double helix. They also show that most, if not all of the ribose rings in both molecules have appreciable 2'-endo puckering. It is unlikely that regA protein distinguishes between these two molecules on the basis of differences in their global conformations in solution. PMID- 1917926 TI - Evaluation of deoxygenated oligosaccharide acceptor analogs as specific inhibitors of glycosyltransferases. AB - The glycosyltransferases controlling the biosynthesis of cell-surface complex carbohydrates transfer glycosyl residues from sugar nucleotides to specific hydroxyl groups of acceptor oligosaccharides. These enzymes represent prime targets for the design of glycosylation inhibitors with the potential to specifically alter the structures of cell-surface glycoconjugates. With the aim of producing such inhibitors, synthetic oligosaccharide substrates were prepared for eight different glycosyltransferases. The enzymes investigated were: A, alpha(1----2, porcine submaxillary gland); B, alpha(1----3/4, Lewis); C, alpha(1- --4, mung bean); D, alpha(1----3, Lex)-fucosyltransferases; E, beta(1----4) galactosyltransferase; F, beta(1----6)-N-acetylglucosaminyltransferase V; G, beta(1----6)-mucin-N-acetylglucosaminyltransferase ("core-2" transferase); and H, alpha(2----3)-sialyltransferase from rat liver. These enzymes all transfer sugar residues from their respective sugar nucleotides (GDP-Fuc, UDP-Gal, UDP-GlcNAc, and CMP-sialic acid) with inversion of configuration at their anomeric centers. The Km values for their synthetic oligosaccharide acceptors were in the range of 0.036-1.3 mM. For each of these eight enzymes, acceptor analogs were next prepared where the hydroxyl group undergoing glycosylation was chemically removed and replaced by hydrogen. The resulting deoxygenated acceptor analogs can no longer be substrates for the corresponding glycosyltransferases and, if still bound by the enzymes, should act as competitive inhibitors. In only four of the eight cases examined (enzymes A, C, F, and G) did the deoxygenated acceptor analogs inhibit their target enzymes, and their Ki values (all competitive) remained in the general range of the corresponding acceptor Km values. No inhibition was observed for the remaining four enzymes even at high concentrations of deoxygenated acceptor analog. For these latter enzymes it is suggested that the reactive acceptor hydroxyl groups are involved in a critical hydrogen bond donor interaction with a basic group on the enzyme which removes the developing proton during the glycosyl transfer reaction. Such groups are proposed to represent logical targets for irreversible covalent inactivation of this class of enzyme. PMID- 1917927 TI - Insertion of the mannitol permease into the membrane of Escherichia coli. Possible involvement of an N-terminal amphiphilic sequence. AB - The in vivo membrane assembly of the mannitol permease, the mannitol Enzyme II (IImtl) of the Escherichia coli phosphotransferase system, has been studied employing molecular genetic approaches. Removal of the N-terminal amphiphilic leader of the permease and replacement with a short hydrophobic sequence resulted in an inactive protein unable to transport mannitol into the cell or catalyze either phosphoenol-pyruvate-dependent or mannitol 1-phosphate-dependent mannitol phosphorylation in vitro. The altered protein (68 kDa) was quantitatively cleaved by an endogenous protease to a membrane-associated 39-kDa fragment and a soluble 28-kDa fragment as revealed by Western blot analyses. Overproduction of the wild type plasmid-encoded protein also led to cleavage, but repression of the synthesis of the plasmid-encoded enzyme by inclusion of glucose in the growth medium prevented cleavage. Several mtlA-phoA gene fusions encoding fused proteins with N-terminal regions derived from the mannitol permease and C-terminal regions derived from the mature portion of alkaline phosphatase were constructed. In the first fusion protein, F13, the N-terminal 13-aminoacyl residue amphiphilic leader sequence of the mannitol permease replaced the hydrophobic leader sequence of alkaline phosphatase. The resultant fusion protein was inefficiently translocated across the cytoplasmic membrane and became peripherally associated with both the inner and outer membranes, presumably via the noncleavable N-terminal amphiphilic sequence. The second fusion protein, F53, in which the N-terminal 53 residues of the mannitol permease were fused to alkaline phosphatase, was efficiently translocated across the cytoplasmic membrane and was largely found anchored to the inner membrane with the catalytic domain of alkaline phosphatase facing the periplasm. This 53-aminoacyl residue sequence included the amphiphilic leader sequence and a single hydrophobic, potentially transmembrane, segment. Analyses of other MtlA-PhoA fusion proteins led to the suggestion that internal amphiphilic segments may function to facilitate initiation of polypeptide trans membrane translocation. The dependence of IImtl insertion on the N-terminal amphiphilic leader sequence was substantiated employing site-specific mutagenesis. The N-terminal sequence of the native permease is Met-Ser-Ser-Asp Ile-Lys-Ile-Lys-Val-Gln-Ser-Phe-Gly.... The following point mutants were isolated, sequenced, and examined regarding the effects of the mutations on insertion of IImtl into the membrane: 1) S3P; 2) D4P; 3) D4L; 4) D4R; 5) D4H; 6) I5N; 7) K6P; and 8) K8P.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1917928 TI - Myosin subfragment-1 interacts with two G-actin molecules in the absence of ATP. AB - The interaction between G-actin and myosin subfragment-1 (S1) has been monitored by pyrenyl-actin fluorescence and light scattering. In low ionic strength buffer and in the absence of ATP the polymerization of G-actin induced by myosin subfragment-1 is preceded by the formation of binary GS and ternary G2S complexes in which S1 interacts tightly in rapid equilibrium (K greater than 10(7) M-1) with one and two G-actin molecules, respectively. Pyrenyl fluorescence of G-actin is enhanced 4-fold in GS and 3-fold in G2S. At concentrations of G-actin and S1 in the micromolar range and above, G2S is the predominant species at G-actin/S1 ratios equal to or greater than 1. The isomer of myosin subfragment-1 carrying the A1 light chain, S1(A1), forms a tighter ternary complex than the isomer S1(A2). Actin-bound ATP is not hydrolyzed upon formation of GS and G2S. In the presence of one molar equivalent or more of myosin subfragment-1/mol of G-actin, in low ionic strength buffer containing no nucleotides, G-actin polymerizes faster in the presence of S1(A1) than in the presence of S1(A2). The interaction of S1 with G-actin is inhibited by the binding of ATP or ADP to S1, ATP having a higher affinity for S1 than ADP. The possible structural similarity of the G2S complex to the F-acto-S1 complex in the rigor state and the potential significance of a ternary (actin)2-myosin interaction for actomyosin-based motility are discussed. PMID- 1917929 TI - Oxidized dimeric Scapharca inaequivalvis. Co-driven perturbation of the redox equilibrium. AB - The dimeric hemoglobin isolated from Scapharca inaequivalvis, HbI, is notable for its highly cooperative oxygen binding and for the unusual proximity of its heme groups. We now report that the oxidized protein, an equilibrium mixture of a dimeric high spin aquomet form and a monomeric low spin hemichrome, binds ferrocyanide tightly which allows for internal electron transfer with the heme iron. Surprisingly, when ferricyanide-oxidized HbI is exposed to CO, its spectrum shifts to that of the ferrous CO derivative. Gasometric removal of CO leads to the oxidized species rather than to ferrous deoxy-HbI. At equilibrium, CO binds with an apparent affinity (p50) of about 10-25 mm of Hg and no cooperativity (20 degrees C, 10-50 mM buffers at pH 6.1). The kinetics of CO binding under pseudo first order conditions are biphasic (t1/2 of 15-50 s at pH 6.1). The rates depend on protein, but not on CO concentration. The nitrite-oxidized protein is not reduced readily in the presence of CO unless one equivalent of ferrocyanide, but not of ferricyanide, is added. We infer that ferrocyanide, produced in the oxidation reaction, is tightly bound to the protein forming a redox couple with the heme iron. CO shifts the redox equilibrium by acting as a trap for the reduced heme. The equilibrium and kinetic aspects of the process have been accounted for in a reaction scheme where the internal electron transfer reaction is the rate-limiting step. PMID- 1917930 TI - Uncoupling of phospholipase C from receptor regulation of [Ca2+]i in T84 colonic cells by prolonged exposure to phorbol dibutyrate. AB - The T84 colonic cell line, a cultured Cl- secretory cell, elevates intracellular free Ca2+ [( Ca2+]i) in a concentration-dependent manner when exposed to carbachol or histamine. As determined with a fluorescence microscope imaging system, exposure of T84 cells to 100 microM carbachol or histamine resulted in an immediate [Ca2+]i rise of approximately 50-80 nM in all cells. Preincubation of monolayers for 1 h or longer with 0.4 microM phorbol 12,13-dibutyrate (PDB) reduced the number of cells which responded to histamine or carbachol and reduced the magnitude of the increase in the responding cells. This effect reached its maximum after 2 h and persisted for at least 24 h of PDB incubation. Binding of quinuclidinyl benzilate, a cholinergic receptor antagonist, indicated that down regulation of external receptors was not an explanation for this effect. Examination of phospholipase C activity in T84 cell membranes showed increased basal activity in PDB-treated compared with control cells. Measurement of inositol phosphates generated by intact cells using myo-[3H]inositol incorporation or receptor binding assays showed that 2 h of incubation with PDB elevated basal levels of inositol 1,4,5-trisphosphate and prevented any further carbachol-induced generation of inositol trisphosphate. Probably as a consequence, both total cell calcium and Ca2+ ionophore-releasable calcium were decreased after 2 h of PDB incubation. Membrane-associated protein kinase C activity was elevated after a 2 h exposure to PDB but was below the level of detection after 24 h with PDB. Protein kinase C antagonists neither duplicated nor blocked the uncoupling of carbachol receptors induced by long term treatment with PDB. The results suggest that prolonged PDB incubation caused uncoupling and elevation of phospholipase C activity from cholinergic and histaminergic receptor regulation resulting in increased basal levels of inositol 1,4,5-trisphosphate. Protein kinase C apparently is not involved directly in the mechanism that leads to these effects. PMID- 1917931 TI - S-farnesylation and methyl esterification of C-terminal domain of yeast RAS2 protein prior to fatty acid acylation. AB - Posttranslational processing/modification is required for membrane localization and activation of ras proteins. In the case of yeast RAS2 protein, we have reported that the process starts with the removal of the initiator methionine followed by polyisoprenylation, removal of 3 amino acid residues from the C terminus, methyl esterification, and fatty acid acylation (Fujiyama, A., and Tamanoi, F. (1990) J. Biol. Chem. 265, 3362-3368). In this study, we demonstrate that polyisoprenylation and methyl esterification of the cysteine residue in the C-terminal domain of the RAS2 protein are involved in the conversion process from precursor form to intermediate form. The polyisoprenoid moiety attached to the RAS2 protein was identified as a 15-carbon farnesyl group through two independent experiments: the release of S-farnesylcysteine with carboxypeptidase Y from the RAS2 protein, and the recovery of radioactive farnesol through methyliodide treatment of the RAS2 protein purified from yeast cells labeled with [3H]mevalonic acid. The farnesyl group attached to the RAS2 protein was detected predominantly in the C-terminal peptide, SGSGGCC, both in the intermediate and in the fatty acid acylated RAS2 protein. The C-terminal cysteine of the intermediate protein is also modified by methyl esterification in a nearly stoichiometric manner. PMID- 1917932 TI - Substrate specificities for yeast and mammalian cAMP-dependent protein kinases are similar but not identical. AB - The substrate specificity of the cAMP-dependent protein kinase (cAPK) from Saccharomyces cerevisiae has been investigated using synthetic peptides corresponding to the local phosphorylation site sequence around Ser-230 in the yeast transcriptional activator ADR1. ADR1 is required for the expression of the glucose-repressible alcohol dehydrogenase. Yeast cAPK (encoded by the TPK1 gene) phosphorylated Ser-230 in the synthetic peptide ADR1-217-234, VRKRYLKKLTRRASFSAQ NH2, with a Km of 5.3 microM compared with 46 microM for LRRASLG (Kemptide). Porcine heart cAPK phosphorylated the ADR1 peptide and Kemptide with the considerable lower Km values of 0.23 and 1.6 microM, respectively. These results indicate that the ADR1 peptide is an excellent substrate for cAPK. Both the yeast and mammalian protein kinases qualitatively shared a number of substrate specificity determinants in common involving residues on the proximal NH2 terminal side and up to the +4 position of the COOH-terminal side of the phosphoacceptor. The mammalian enzyme, however, had a much higher affinity for its substrates than did the yeast enzyme. In addition, the yeast and mammalian enzymes displayed several quantitative differences in their preferences for particular peptide substrates. In particular, the mammalian enzyme strongly preferred substrates with NH2-terminal extensions beyond the -4 position relative to the phosphoacceptor. These results suggest that all eukaryotic cAPKs recognize similar but not identical substrate specificity determinants. They also suggest that the different affinities for substrates that inhere to the individual enzymes could influence their physiological roles. PMID- 1917933 TI - Expression and regulation of UDP-glucuronate: neolactotetraosylceramide glucuronyltransferase in the nervous system. AB - Sulfoglucuronyl glycolipids (SGGLs) are temporally and spatially regulated molecules present in the nervous system during its development. The characteristics of the rat brain enzyme glucuronyltransferase involved in the biosynthesis of SGGLs have been described. The enzyme catalyzes the transfer of glucuronic acid (GlcA) from UDP-GlcA to terminal galactose of the neolacto (type 2) series of glycolipids to form beta 1-3-linked glucuronyl neolacto glycolipids. The enzyme was highly specific for the neolacto series of acceptor glycolipids, neolactotetraosylceramide (nLcOse4Cer), neolactohexaosylceramide (nLcOse6-Cer), and neolactooctaosylceramide (nLcOse8Cer) and was different from the drug inducible phenol:GlcA transferase. Considerable activity of GlcA transferase was present in the adult rat cerebral cortex, even though SGGLs almost completely disappeared from the cortex by postnatal day 15. In the cerebellum, although levels of SGGLs increased with development, the specific activity of GlcA transferase declined. The results indicated that GlcA transferase was not a regulatory enzyme controlling the expression of SGGLs. Measurements of the levels of nLcOse4Cer and nLcOse6Cer in these neural tissues indicated that the availability of these precursors may regulate the differential expression of SGGLs seen previously. GlcA transferase was significantly reduced in the cerebellar Purkinje cell degenerating murine mutant (pcd/pcd), which is consistent with the loss of SGGLs in the cerebellum of this mutant and specific association of these glycolipids with Purkinje cells. PMID- 1917934 TI - Functional domains of Bacillus thuringiensis insecticidal crystal proteins. Refinement of Heliothis virescens and Trichoplusia ni specificity domains on CryIA(c). AB - Insecticidal crystal proteins (delta-endotoxins), CryIA(a) and CryIA(c), from Bacillus thuringiensis are 82% homologous. Despite this homology, CryIA(c) was determined to have 10-fold more insecticidal activity toward Heliothis virescens and Trichoplusia ni than CryIA(a). Reciprocal recombinations between these two genes were performed by the homolog-scanning technique. The resultant mutants had different segments of their primary sequences exchanged. Bioassays with toxin proteins from these mutants revealed that amino acids 335-450 on CryIA(c) are associated with the activity against T. ni, whereas amino acids 335-615 on the same toxin are required to exchange full H. virescens specificity. One chimeric protein toxin, involving residues 450-612 from CryIA(c), demonstrated 30 times more activity against H. virescens than the native parental toxin, indicating that this region plays an important role in H. virescens specificity. The structural integrity of mutant toxin proteins was assessed by treatment with bovine trypsin. All actively toxic proteins formed a 65-kDA trypsin-resistant active toxic core, similar to the parental CryIA(c) toxin, indicating that toxin protein structure was not altered significantly. Contrarily, certain inactive mutant proteins were susceptible to complete protease hydrolysis, indicating that their lack of toxicity may have been due to structural alterations. PMID- 1917935 TI - Identification of sequences within the murine granulocyte-macrophage colony stimulating factor mRNA 3'-untranslated region that mediate mRNA stabilization induced by mitogen treatment of EL-4 thymoma cells. AB - Phorbol esters (TPA) and concanavalin A (ConA) are known to induce granulocyte macrophage colony-stimulating factor (GM-CSF) production in murine thymoma EL-4 cells by mRNA stabilization. The role of the 3'-untranslated region (3'-UTR) in GM-CSF mRNA stabilization induced by TPA and ConA in EL-4 cells was examined by transfection studies using chloramphenicol acetyltransferase (CAT) constructions. The GM-CSF 3'-UTR contains a 63-nucleotide region at its 3' end with repeating ATTTA motifs which is responsible for mRNA degradation in a variety of cell types (Shaw, G., and Kamen, R. (1986) Cell 46, 659-666). We produced constructs containing most of the GM-CSF 3'-UTR (303 nucleotides, pRSV-CATgm) or the 3' terminal AT-rich region (116 nucleotides, pRSV-CATau) and measured CAT enzyme activity and CAT mRNA after transient transfection into EL-4 and NIH 3T3 cells. Low levels of CAT activity were seen in both cells with either plasmid compared with levels of CAT activity obtained with pRSV-CAT. TPA treatment caused an approximately 10-fold increase in CAT activity and mRNA in EL-4 cells transfected with pRSV-CATgm. No increases were seen in EL-4 cells transfected with pRSV-CATau or pRSV-CAT. No response to TPA was detected in transfected NIH 3T3 cells, indicating that the response to TPA is relatively cell-specific. There was no increase in CAT activity after ConA treatment in EL-4 or NIH 3T3 cells transfected with any of the constructs suggesting that the GM-CSF 3'-UTR lacks elements that can respond alone to ConA. Nuclear run-on and actinomycin D chase experiments in EL-4 cells showed that TPA induces CAT activity via mRNA stabilization. By linker-substitution mutagenesis we show that TPA inducibility depends on a 60-nucleotide region of the 3'-UTR whose 5' end is located 160 nucleotides upstream of the 5' end of the AU-rich region. PMID- 1917936 TI - Negative regulation of cell proliferation by mevalonate or one of the mevalonate phosphates. AB - The role of mevalonate and its products in the regulation of cellular proliferation was examined using 6-fluoromevalonate (Fmev), a compound that blocks the conversion of mevalonate pyrophosphate to isopentenyl pyrophosphate. Fmev suppressed DNA synthesis by a variety of transformed and malignant T cell, B cell, and myeloid cell lines. In contrast to results previously reported with mitogen-stimulated human peripheral blood T cell DNA synthesis, low concentrations of low density lipoprotein (LDL) alone could not restore proliferation to these cell lines. The same concentrations of LDL were able to provide sufficient cholesterol and support the growth of all cell lines when mevalonate synthesis was blocked with a specific inhibitor of 3-hydroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase, lovastatin. Fmev-mediated inhibition was totally prevented in some but not all cell lines when the concentration of exogenous LDL was increased 5-10-fold above that required to permit proliferation of lovastatin-blocked cells. Residual HMG-CoA reductase activity of cells cultured with LDL inversely correlated with the restoration of growth to Fmev-blocked cultures. Confirmation of the critical role of HMG-CoA reductase activity and mevalonate synthesis in the inhibition of cellular proliferation by Fmev was obtained by demonstrating that the specific inhibitor of this enzyme, lovastatin, restored proliferation of Fmev-blocked cells. Furthermore, supplementation of cultures with mevalonate, the product of HMG-CoA reductase activity, markedly inhibited proliferation of Fmev-blocked cells. These findings indicate that mevalonate or one of the mevalonate phosphates, which accumulates in Fmev-blocked cells, is a critical negative regulator of cellular proliferation. PMID- 1917937 TI - Inhibition and stimulation of c-myc gene transcription by insulin in rat hepatoma cells. Insulin alters the intragenic pausing of c-myc transcription. AB - One of insulin's least studied actions is its ability to induce DNA synthesis and cell division. In rat H4IIE hepatoma cells insulin, acting through its own receptor, stimulates cell division. However, little is known about the molecular mechanisms involved in this effect. The proto-oncogene c-myc is a cellular gene which when expressed at abnormal levels is often associated with the process of tumorigenesis. Expression of the normal cellular myc gene may be necessary for growth factor-induced cell cycling. In the present work, insulin was shown to regulate cellular accumulation and transcription of the c-myc gene in rat hepatoma cells. The control of c-myc by insulin was complex, with an initial induced decrease in c-myc transcription to 50% of control values at 15 and 30 min. This was followed by an increase in transcription of about 3-fold by 60-120 min. Similar to the initial inhibitory effect of insulin, the protein synthesis inhibitors cycloheximide or anisomycin decreased c-myc transcription. However, there was no secondary induction of c-myc transcription by protein synthesis inhibitors. The effects of both insulin and protein synthesis inhibitors were shown to be through alterations in intragenic pausing of transcription of the sense mRNA, not through changes initiation of transcription. PMID- 1917938 TI - Plasma 1-palmitoyl-2-linoleoyl phosphatidylcholine. Evidence for extensive phospholipase A1 hydrolysis and hepatic metabolism of the products. AB - 1-Palmitoyl-2-linoleoyl phosphatidylcholine (PLPC) labeled in either the choline, glycerol, palmitate, or linoleate component in reconstituted rat high density lipoprotein (rHDL), was administered by vein to rats with bile fistula and taurocholate infusion. PLPC disappeared from plasma in a monoexponential fashion with a half-life of 50 min. A small fraction, about 14%, of PLPC disappearance was due to removal of linoleate from the sn-2 ester bond to form plasma cholesterol esters, presumably by lecithin-cholesterol acyltransferase. Otherwise, nearly all of the PLPC components that disappeared from blood in 1 h were recovered in the liver. The choline, glycerol, and linoleate components appeared predominantly in hepatic phosphatidylcholine (PC). These three components remained together in the liver with similar fractions of each in individual PC molecular species, most notably 1-stearoyl-2-linoleoyl-PC and dilinoleoyl-PC as well as PLPC. However, the palmitate component was spread among hepatic triglyceride, free fatty acid, other phospholipids, and all palmitate containing molecular species of PC. Less than 2% of any administered PLPC component appeared in 1-stearoyl-2-arachidonyl-PC, the major species by mass in the liver. The palmitate component from plasma PLPC appeared in biliary PC at a more rapid rate than glycerol and linoleate components; the latter components appeared in bile in identical fashion. The results show that about two-thirds of plasma PLPC disappearance is due to phospholipase A1 hydrolysis, probably hepatic lipase. The putative produce, 2-linoleoyl-lysoPC, is efficiently reacylated with a saturated fatty acid in the liver, conserving PC. PMID- 1917939 TI - Structural and sequence elements important for recognition of Escherichia coli formylmethionine tRNA by methionyl-tRNA transformylase are clustered in the acceptor stem. AB - We show that the structure and/or sequence of the first three base pairs at the end of the amino acid acceptor stem of Escherichia coli initiator tRNA and the discriminator base 73 are important for its formylation by E. coli methionyl-tRNA transformylase. This conclusion is based on mutagenesis of the E. coli initiator tRNA gene followed by measurement of kinetic parameters for formylation of the mutant tRNAs in vitro and function in protein synthesis in vivo. The first base pair found at the end of the amino acid acceptor stem in all other tRNAs is replaced by a C.A. "mismatch" in E. coli initiator tRNA. Mutation of this C.A. to U:A, a weak base pair, or U.G., a mismatch, has little effect on formylation, whereas mutation to C:G, a strong base pair, has a dramatic effect lowering Vmax/Kappm by 495-fold. Mutation of the second basepair G2:C71 to U2:A71 lowers Vmax/Kappm by 236-fold. Replacement of the third base-pair C3:G70 by U3:A70, A3:U70, or G3:C70 lowers Vmax/Kappm by about 67-, 27-, and 30-fold, respectively. Changes in the rest of the acceptor stem, dihydrouridine stem, anticodon stem, anticodon sequence, and T psi C stem have little or no effect on formylation. PMID- 1917940 TI - Mutants of initiator tRNA that function both as initiators and elongators. AB - We describe the effect of mutations in the acceptor stem of Escherichia coli initiator tRNA on its function in vivo. The acceptor stem mutations were coupled to mutations in the anticodon sequence from CAU----CUA to allow functional studies on the mutant tRNAs in initiation and in elongation in vivo. We show that, with one exception, there is a good correlation between the kinetic parameters for formylation of the mutant tRNAs in vitro (preceding paper, Lee, C.P., Seong, B. L., and RajBhandary, U.L. (1991) J. Biol. Chem. 266, 18012-18017) and their activity in initiation in vivo. These results suggest an important role for formylation of initiator tRNA in its function in initiation, at least when it is aminoacylated with glutamine as is the case with the mutant tRNAs used here. Mutant tRNAs that have a base pair between nucleotides 1 and 72 at the top of the acceptor stem function as elongators, as analyzed by their ability to suppress an amber mutation in the E. coli beta-galactosidase gene. One of these mutants is also quite active in initiation. Thus, activities of a tRNA in initiation and elongation steps of protein synthesis are not mutually exclusive. Using a mRNA with two in frame UAG codons, we show that this mutant tRNA can both initiate protein synthesis from the upstream UAG and suppress the down-stream UAG. We discuss the potential use of tRNAs with such "dual" functions in tightly regulated expression of genes for proteins in E. coli. PMID- 1917941 TI - Transcription from a bacteriophage T4 middle promoter using T4 motA protein and phage-modified RNA polymerase. AB - The bacteriophage T4 motA protein is required for transcription from T4 middle promoters. These promoters, which contain the Escherichia coli promoter consensus sequence at the -10 region (TATAAT) but a unique sequence centered at -30 ((a/t)(a/t)TGCTT(t/c)A) (Guild, N., Gayle, M., Sweeney, R., Hollingsworth, T., Modeer, T., and Gold, L. (1988) J. Mol. Biol. 199, 241-258), become active about 2 min after infection, a time when the host RNA polymerase has been modified by phage proteins. This paper shows that motA protein binds to a T4 middle promoter in vitro and that the addition of the motA protein allows in vitro transcription from this promoter by T4-modified RNA polymerase. The T4 motA gene was cloned into a multicopy plasmid that complemented T4 motA mutants in vivo. MotA protein, partially purified from cells containing a motA+ plasmid, specifically retarded the electrophoretic mobility of an oligomer containing the T4 middle promoter located 195 bases upstream of uvsX (PuvsX). RNA polymerase isolated from infected cells during T4 middle gene expression supported in vitro transcription from PuvsX only when fractions containing the motA protein were added. In contrast, unmodified host RNA polymerase catalyzed the synthesis of minor amounts of RNA from PuvsX, but this synthesis was not motA dependent. Thus, the in vitro transcription system described here provides the basis for a detailed study of the phage and host factors needed to regulate T4 middle gene expression. PMID- 1917942 TI - Transcriptional regulation of the apolipoprotein A-I gene. Species-specific expression correlates with rates of gene transcription. AB - Previous studies have shown that the abundance of apoA-I mRNA in liver and intestine correlates with a 2-3-fold species-specific difference in the plasma concentration of high density lipoprotein and apoA-I. In order to determine the role of gene transcription in regulating the tissue, steady state apoA-I mRNA abundance nuclear run-on assays were conducted using nuclei from two species of nonhuman primates. The transcriptional activity expressed as the ratio of apoA-I signal intensity to that for the constitutively expressed glyceraldehyde-3 phosphate dehydrogenase was calculated for seven individual animals in each of the two nonhuman primate species. The African green monkey showed a ratio of 4.18 +/- 0.35, and the cynomolgus monkey showed 2.03 +/- 0.13 (n = 7, p less than 0.004). To identify possible cis-acting elements that may be involved in transcriptional regulation of the apoA-I gene, a portion of the apoA-I regulatory region, corresponding to nucleotides -231 to +263 (where +1 is the start site of transcription), was isolated from both species using the polymerase chain reaction. The nucleotide sequence of this region was compared between monkey species, as well as with the same region from the apoA-I gene isolated from human genomic DNA. In this region, the African green monkey apoA-I gene showed 95% similarity, whereas the cynomolgus monkey showed 94% similarity to the human sequence. Although a high degree of sequence similarity was observed among all species, numerous sequence specific differences were noted in the first intron between the two primate species and between nonhuman and human primate sequences. Results from studies measuring relative promoter strength indicated that the African green monkey 5'-regulatory region had a consistently higher level of activity (1.4-3.0-fold) than the same region from the cynomolgus monkey. Interestingly, the African green monkey promoter also showed a significantly higher transcriptional activity than the human or rabbit promoter, suggesting the presence of a nonhuman primate specific cis-acting element(s) regulating apoA-I gene expression. These results demonstrate that a portion of the species-specific difference in apoA-I gene expression may be explained by sequence divergence in the 5'-regulatory region including exon/intron 1 of the apoA-I gene. PMID- 1917943 TI - Regulatory element analysis and structural characterization of the human sarcomeric mitochondrial creatine kinase gene. AB - Creatine kinase (EC 2.7.3.2) (CK) isoenzymes are crucial to energy metabolism, particularly in tissues with high energy requirements. Nuclear genes encode four known CK subunits: cytoplasmic muscle, cytoplasmic brain, ubiquitous mitochondrial (uMtCK), and sarcomeric mitochondrial (sMtCK). Herein, we report the isolation and complete structural characterization of the human sMtCK gene. It contains 11 exons and encompasses more than 37 kilobase pairs (kb). The sites of exon localization in the sMtCK-coding region and their precise sizes are identical with the human uMtCK gene. The translation start codon is in the third exon and lies 17 kb from the transcription start site. The human sMtCK gene is located on chromosome 5. Sequence analysis of the sMtCK genomic upstream sequences reveals a typical TATAA box within the 80 base pairs (bp) that, by transfection experiments, are sufficient to promote expression of chimeric plasmids with the chloramphenicol acetyltransferase reporter. Cis-acting sequences in a fragment containing 3360 bp of upstream sequence, the first exon, and 750 bp of the first intron are sufficient to mediate tissue-specific expression. However, these sequences only partially regulate induction of sMtCK expression in differentiating mouse myoblasts. MEF1/MYOD and MEF2 sequence motifs present in the sMtCK gene are not sufficient to regulate differentiation-specific expression. The sMtCK gene contains sequences homologous to several motifs that are shared among some nuclear genes encoding mitochondrial proteins and that may be essential for the coordinated activation of these genes during mitochondrial biogenesis. PMID- 1917944 TI - Transforming growth factor-beta 1 stimulates glucose uptake and the expression of glucose transporter mRNA in quiescent Swiss mouse 3T3 cells. AB - Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional polypeptide that regulates the proliferation and differentiation of various types of animal cells. TGF-beta 1 stimulated glucose uptake and the expression of a brain-type glucose transporter (GLUT1) mRNA in quiescent mouse 3T3 cells. TGF-beta 1 also synergistically stimulated these activities when given together with calf serum, phorbol ester, fibroblast growth factor, or epidermal growth factor. The increases in glucose uptake and the GLUT1 mRNA level were induced by picomolar concentrations of TGF-beta 1 within 3 h of stimulation, reached a peak between 6 and 9 h, and then decreased gradually to basal levels before an increase in DNA synthesis. The stimulation of GLUT1 mRNA expression was completely abolished by actinomycin D, but was not affected by cycloheximide, suggesting that new protein synthesis was not required for the expression of GLUT1 mRNA. TGF-beta 1 had little mitogenic activity and did not affect serum-induced DNA synthesis in quiescent 3T3 cells. However, it stimulated DNA synthesis synergistically when given with fibroblast growth factor, epidermal growth factor, phorbol ester, or insulin. These results suggest that TGF-beta 1 mediates the stimulation of glucose uptake, GLUT1 mRNA expression, and DNA synthesis via a pathway(s) and cellular components distinct from those for other growth factors. The possible role of the TGF-beta 1-induced stimulation of glucose transport activity in the control of mouse fibroblast proliferation is also discussed. PMID- 1917945 TI - Interleukin-4 proliferative signal transduction involves the activation of a tyrosine-specific phosphatase and the dephosphorylation of an 80-kDa protein. AB - Interleukin-4 (IL-4) is a cytokine that expresses its biological effects by binding to specific membrane receptors. Although the diverse biological properties of this molecule have been characterized extensively the biochemical mechanisms by which extracellular binding events lead to biological responses remain unclear. IL-4 can stimulate the proliferation of several hemopoietic cell types, and we have taken advantage of its ability to induce the growth of leukemic cell lines to investigate the role that protein phosphorylation events might play in IL-4 mitogenic signal transduction. We show that the addition of IL 4 to several leukemic cell lines of different origin causes the rapid dephosphorylation of an 80-kDa phosphoprotein (p80) from tyrosine residues. This event occurs in a dose-responsive manner closely correlating to that of biological activity, and both are blocked by an anti-IL-4-specific antiserum. The ability of sodium orthovanadate to prevent IL-4-induced dephosphorylation of p80 suggests that this event is mediated by a protein-tyrosine-phosphatase (EC 3.1.3.48). The importance of the role that tyrosine-specific dephosphorylation plays in mediating IL-4 mitogenic signal transduction is substantiated by the ability of sodium orthovanadate in cell culture to block effectively IL-4-induced proliferation at doses that enhance the proliferation stimulated by either granulocyte-macrophage colony-stimulating factor or interleukin-3. PMID- 1917947 TI - Purification, characterization, and molecular cloning of lactonizing lipase from Pseudomonas species. AB - An extracellular lipase catalyzing the synthesis of macrocyclic lactones in anhydrous organic solvents was purified to homogeneity from Pseudomonas nov. sp. 109, and characterized. The lipase showed a pI of 5.3 on isoelectric focusing and a Mr of 29,000 +/- 1,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With respect to substrate specificity, optimum chain length for acyl moiety varied depending on the type of reaction catalyzed: C18 in monomer lactone formation, C11 or shorter in dimer lactone formation, and C8 in ester hydrolysis. The amino-terminal 19 amino acid residues of the purified lipase were determined as Ser-Thr-Tyr-Thr-Gln-Thr-Lys-Tyr-Pro-Ile-Val-Leu-Ala-His-Gly-Met-Leu Gly- Phe, and the gene encoding the lipase was identified by hybridization to a synthetic 20-nucleotide probe, cloned, and sequenced. Nucleotide sequence analysis predicted a 311-amino acid open reading frame, a putative ribosome binding site, and a 26-amino acid sequence at the amino terminus of the sequence that is not found in the mature protein. This 26-amino acid sequence has many of the characteristics common to known signal peptides. The lipase gene encoded a sequence of Val-Asn-Leu-Ile-Gly-His-Ser-His-Gly-Gly which is very well conserved among lipases, and showed 38-40% overall homology to the amino acid sequences of lipases from Pseudomonas fragie and Pseudomonas cepacia, but showed little homology to those of other lipases, suggesting that some structural features are required for catalyzing macrocyclic lactone synthesis in organic solvents and are restricted to lipases of the Pseudomonas origin. PMID- 1917946 TI - Interferon-gamma-induced astrocyte class II major histocompatibility complex gene expression is associated with both protein kinase C activation and Na+ entry. AB - Astrocytes can be induced by interferon-gamma (IFN-gamma) to express class II major histocompatibility complex (MHC) antigens. This study was undertaken to elucidate the intracellular signaling pathways involved in IFN-gamma induction of class II MHC. We examined the effects of Na+/H+ antiporter and protein kinase C (PKC) inhibitors on class II expression and Na+ influx in astrocytes. We found that amiloride and ethyl isopropylamiloride, inhibitors of Na+/H+ exchange, blocked IFN-gamma-induced class II gene expression. IFN-gamma stimulated Na+ influx, and this increased influx was inhibited by amiloride. Treatment of astrocytes with the PKC inhibitor H7 also blocked the increase in Na+ uptake induced by IFN-gamma, indicating that IFN-gamma-induced PKC activation is required for subsequent Na+ influx. IFN-gamma treatment produced an increase of total PKC activity, which was associated with a rapid translocation of PKC activity from cytosolic to particulate fraction. H7 and another PKC inhibitor, staurosporine, inhibited IFN-gamma-induced class II gene expression. However, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, a potent PKC activator, did not affect class II expression. Taken together, our data indicate that both IFN-gamma induced PKC activation and Na+ influx are required for class II MHC expression in astrocytes but that activation of PKC alone is not sufficient for ultimate expression of this gene. PMID- 1917948 TI - Motor protein independent binding of endocytic carrier vesicles to microtubules in vitro. AB - We have established an in vitro assay to characterize the binding of endocytic carrier vesicles to microtubules. Magnetic beads coated with microtubules were used as an affinity matrix. A fraction from nocodazole-treated cells enriched in endocytic carrier vesicles, labeled with internalized horseradish peroxidase, was used in the binding experiments. Binding of the endocytic carrier vesicles to microtubules in vitro was cytosol-dependent. This activity of cytosolic factors was saturable, heat-sensitive, and insensitive to N-ethyl-maleimide. Binding was sensitive to GTP and ATP. Addition of neuronal microtubule-associated proteins completely abolished binding of the endocytic organelles to microtubules. This binding was independent of the cytosolic microtubule-based motor proteins kinesin and cytoplasmic dynein, since cytosol depleted of these proteins remained fully active. Microtubule-binding proteins from HeLa cells, however, stimulated the interaction of endocytic carrier vesicles with microtubules. Trypsinized vesicles could no longer bind to microtubules in the presence of cytosol. These results suggest that cytosolic microtubule-binding proteins, other than the known microtubule-based motor proteins, as well as membrane proteins are involved in the nucleotide-dependent interaction of endocytic carrier vesicles with microtubules. PMID- 1917949 TI - Identification of discontinuous von Willebrand factor sequences involved in complex formation with botrocetin. A model for the regulation of von Willebrand factor binding to platelet glycoprotein Ib. AB - We have used proteolytic fragments and overlapping synthetic peptides to define the domain of von Willebrand factor (vWF) that forms a complex with botrocetin and modulates binding to platelet glycoprotein (GP) Ib. Both functions were inhibited by the dimeric 116-kDa tryptic fragment and by its constituent 52/48 kDa subunit, comprising residues 449-728 of mature vWF, but not by the dimeric fragment III-T2 which lacks amino acid residues 512-673. Three synthetic peptides, representing discrete discontinuous sequences within the region lacking in fragment III-T2, inhibited vWF-botrocetin complex formation; they corresponded to residues 539-553, 569-583, and 629-643. The 116-kDa domain, with intact disulfide bonds, exhibited greater affinity for botrocetin than did the reduced and alkylated 52/48-kDa molecule, and both fragments had significantly greater affinity than any of the inhibitory peptides. Thus, conformational attributes, though not strictly required for the interaction, contribute to the optimal functional assembly of the botrocetin-binding site. Accordingly, 125I-labeled botrocetin bound to vWF and to the 116-kDa fragment immobilized onto nitrocellulose but not to equivalent amounts of the reduced and alkylated 52/48 kDa fragment; it also bound to the peptide 539-553, but only when the peptide was immobilized onto nitrocellulose at a much greater concentration than vWF or the proteolytic fragments. These studies demonstrate that vWF interaction with GP Ib may be modulated by botrocetin binding to a discontinuous site located within residues 539-643. The finding that single point mutations in Type IIB von Willebrand disease are located in the same region of the molecule supports the concept that this domain may contain regulatory elements that modulate vWF affinity for platelets at sites of vascular injury. PMID- 1917950 TI - Transactivation functions facilitate the disruption of chromatin structure by estrogen receptor derivatives in vivo. AB - The activation of gene transcription by nuclear receptors is invariably associated with alterations in chromatin structure at hormone-responsive elements of target genes. To identify the molecular functions underlying receptor-mediated chromatin structure alterations we have evaluated the effects of DNA binding and transactivation of estrogen receptor derivatives on the promoter chromatin structure of estrogen-responsive reporter minichromosomes in Saccharomyces cerevisiae. We report here that the DNase I-hypersensitive chromatin structure at the promoter region is not simply a consequence of estrogen receptor binding to estrogen-responsive elements but is greatly enhanced by transactivation functions. These chromatin structure alterations are dependent on the presence of more than one estrogen-responsive element as well as downstream promoter sequences and appear to be correlated with transcriptional competence of the promoter. Our results imply that a disruption of chromatin structure at promoters is associated with the establishment of active transcription complexes. Since RNA polymerase cannot initiate transcription on nucleosomal DNA in vitro (Lorch, Y., Lapointe, J.W., and Kornberg, R.D. (1987) Cell 49, 203-210) this local disruption of chromatin structure may represent a nucleosome-free window, allowing initiation to occur in vivo. PMID- 1917951 TI - Actin polymerization promoted by a heptapeptide, an analog of the actin-binding S site on myosin head. AB - Polymerization of G-actin to F-actin was indicated by an increase in light scattering intensity after the addition of a heptapeptide (Ile-Arg-Ile-Cys(MT) Arg-Lys-Gly-OEt), an analog of the actin-binding S-site on S-1 heavy chain. The half-maximal concentration of the heptapeptide which induced an increase in the light-scattering intensity at 25 degrees C was about 110 microM, which was in the range of the dissociation constant of this peptide with F-actin. The polymerization of G-actin to F-actin by binding of the heptapeptide was further demonstrated by ultracentrifugal separation, Pi liberation, and electron microscopy. The polymerization of G-actin was induced only by the heptapeptide, but not by fragments of the heptapeptide. The well known acceleration of polymerization of G-actin by the myosin head may be due to the binding of G-actin with the S-site on the myosin head. PMID- 1917952 TI - Production of multimeric forms of CD4 through a sugar-based cross-linking strategy. AB - We have developed a three-step cross-linking procedure that is specifically targeted at the carbohydrate on a protein and applied it to CD4 as a model system for studying the role of multivalent interactions in function. In the first step CD4 was oxidized with periodate, creating aldehydes that served as targets for the subsequent chemistry. Next the aldehydes were modified with cystamine, converting the reactive group into a thiol. Finally cross-linking through the thiol moiety was generated with the homobifunctional cross-linker bismaleimidohexane. With this procedure, approximately 60% of the CD4 was converted into higher molecular weight complexes that were soluble and retained function as assessed by glycoprotein gp120 binding activity. CD4 dimers and tetramers by mass were 4 and 15 times as active as CD4 monomer in blocking virus infection with HTLV-IIIB in an in vitro cellular assay. The cross-linking chemistry provides an efficient method for producing homomultimers of a glycoprotein. PMID- 1917953 TI - Induction of the proliferative phenotype in differentiated myogenic cells by hypoxia. AB - The effect of cellular differentiation on the response of cells to hypoxic stress has been evaluated using the myogenic cell line BC3H1. Aerobic myocytes were predominantly in G0/G1 of the cell cycle and could be induced into S and G2/M of the cell cycle only by replating in high serum-containing medium at subconfluent cell density. In contrast, hypoxic myocytes demonstrated marked progression into S and G2/M upon reoxygenation without replating in the presence of serum. This modulation of myocytes by hypoxia was suggested further by the induction of 100 kDa and 9-kDa proteins (PSP 100 and PSP 9) which were otherwise only detectable in myoblasts. Two-dimensional gel analysis of newly synthesized proteins demonstrated that the five major glucose/oxygen-regulated proteins (GRP/ORP 260, 150, 100, 80, and 33) were induced in hypoxic myogenic cells independent of their state of differentiation. In addition to the GRP/ORPs, synthesis of 20 and 23 other major proteins was influenced in myocytes and myoblasts, respectively. The bulk of these alterations in myoblasts (70%) were inhibitions. In contrast, 75% of the alterations in myocyte protein synthesis were either enhancements or inductions. The data show that hypoxia can modulate the myocyte phenotype and invoke proliferative characteristics. Moreover, the data suggest that ischemia will have a different effect on and prognosis for tissues with a high mitotic index compared with differentiated tissues. PMID- 1917954 TI - Mechanisms of inhibition by apolipoprotein C of apolipoprotein E-dependent cellular metabolism of human triglyceride-rich lipoproteins through the low density lipoprotein receptor pathway. AB - The mechanism of inhibition by apolipoprotein C of the uptake and degradation of triglyceride-rich lipoproteins from human plasma via the low density lipoprotein (LDL) receptor pathway was investigated in cultured human skin fibroblasts. Very low density lipoprotein (VLDL) density subfractions and intermediate density lipoprotein (IDL) with or without added exogenous recombinant apolipoprotein E-3 were used. Total and individual (C-I, C-II, C-III-1, and C-III-2) apoC molecules effectively inhibited apoE-3-mediated cell metabolism of the lipoproteins through the LDL receptor, with apoC-I being most effective. When the incubation was carried out with different amounts of exogenous apoE-3 and exogenous apoC, it was shown that the ratio of apoE-3 to apoC determined the uptake and degradation of VLDL. Excess apoE-3 overcame, at least in part, the inhibition by apoC. ApoC, in contrast, did not affect LDL metabolism. Neither apoA-I nor apoA-II, two apoproteins that do not readily associate with VLDL, had any effect on VLDL cell metabolism. The inhibition of VLDL and IDL metabolism cannot be fully explained by interference of association of exogenous apoE-3 with or displacement of endogenous apoE from the lipoproteins. IDL is a lipoprotein that contains both apoB-100 and apoE. By using monoclonal antibodies 4G3 and 1D7, which specifically block cell interaction by apoB-100 and apoE, respectively, it was possible to assess the effects of apoC on either apoprotein. ApoC dramatically depressed the interaction of IDL with the fibroblast receptor through apoE, but had only a moderate effect on apoB-100. The study thus demonstrates that apoC inhibits predominantly the apoE-3-dependent interaction of triglyceride-rich lipoproteins with the LDL receptor in cultured fibroblasts and that the mechanism of inhibition reflects association of apoC with the lipoproteins and specific concentration-dependent effects on apoE-3 at the lipoprotein surface. PMID- 1917955 TI - Identification of a glucocorticoid response element contributing to the constitutive expression of the rat liver alpha 1-inhibitor III gene. AB - alpha 1-Inhibitor III (alpha 1 I3), a broad range plasma proteinase inhibitor, is synthesized with striking tissue specificity in rat livers. The gene is expressed strongly in periportal hepatocytes of healthy adults and less abundantly in regions near the centrilobular vein. This expression pattern is suggestive of a concentration gradient of a blood-borne hormone that enters through the portal vein and diffuses across the lobe toward the centrilobular vein. The alpha 1 I3 gene was known to be regulated both by glucocorticoids and interleukin 6, and therefore the hypothesis was tested that the normal constitutive expression of this gene depended on glucocorticoids. alpha 1 I3 mRNA levels in the livers of hypophysectomized rats with low endogenous glucocorticoid levels were only about 20% of those in control rat livers. Injection of exogenous glucocorticoids reconstituted hepatic alpha 1 I3 mRNA levels up to 64% of their original values in a dose-dependent manner. Similarly, treatment of FAZA rat hepatoma cells with the synthetic glucocorticoid dexamethasone induced alpha 1 I3 mRNA levels in a dose-dependent manner. Taken together these data suggested that glucocorticoids are required for the constitutive high level expression of this gene in normal adult rat livers. A series of 5' deletion constructs and linker scanning mutants of the promoter upstream region were produced and transfected into FAZA cells. A functional glucocorticoid response element was mapped between -168 and -151 base pairs 5' of the transcription start site. This element conforms with an inverted consensus glucocorticoid response element (GRE) but differs in two positions essential for protein DNA interaction between the GRE and the glucocorticoid receptor (GR). The induction of alpha 1 I3 gene promoter region constructs by dexamethasone was abolished by the receptor antagonist RU486, indicating that the GR participated in the activation of the alpha 1 I3 gene. In DNase I footprinting experiments with nuclear protein extracts from untreated and dexamethasone treated FAZA cells, similar extents of alpha 1 I3 promoter upstream sequences were protected, indicating that proteins capable of binding in the glucocorticoid response-mediating element (GME) region were present before and after arrival of the hormonal signal. However, a purified recombinant fragment of the GR which contained essentially only its DNA binding domain was unable to bind at the GME although it interacted strongly with a consensus GRE sequence. PMID- 1917956 TI - Phosphorylation of transfected wild type and mutated progesterone receptors. AB - An expression vector encoding wild type or mutated forms of the rabbit progesterone receptor was transfected into COS-7 cells and phosphorylation was studied by incubation with 32Pi followed by specific immunoprecipitation. The features of phosphorylation of the wild type receptor were identical to those previously observed in uterine cells: there was a basal level of phosphorylation which was increased approximately 7-fold by incubation with the hormone. The hyperphosphorylated receptor had decreased electrophoretic mobility ("upshift"). These experiments thus showed that the presence of the receptor specific kinase is not restricted to the target cells. Cleavage of the receptor by hydroxylamine and cyanogen bromide, and use of receptor mutants deleted in the N-terminal region, showed the absence of any detectable phosphorylation downstream from amino acid 520 (thus in the DNA and steroid binding domains). The majority of the phosphorylation sites were localized between amino acids 166 and 520. This localization was similar for basal and hormone-induced phosphorylation. DNA binding and hormone-induced hyperphosphorylation were not directly related, since deletion of the first zinc finger provided a hyperphosphorylated receptor. We showed that the constitutive receptor (totally deleted in the steroid binding region) exhibited only a low basal level of phosphorylation, and antagonist RU 486-receptor complexes were found to be hyperphosphorylated, leading us to conclude that the active form of the receptor was not the hyperphosphorylated one. Moreover receptor down regulation and hormone-induced receptor hyperphosphorylation were two independent phenomena. Basal phosphorylation was observed for both cytoplasmic and nuclear mutants, whereas nuclear localization was necessary but not sufficient for hyperphosphorylation. Finally, the second finger region and the hormone binding domain, which are necessary for receptor hyperphosphorylation, may be involved in the hormonally induced increased affinity of the receptor toward its kinase. PMID- 1917957 TI - Identification of the glucocorticoid suppressible mitogen from rat hepatoma cells as an angiogenic platelet-derived growth factor A-chain homodimer. AB - We have previously shown that BDS.1 rat hepatoma cells are hypersensitive to the antiproliferative effects of glucocorticoids, and secrete a glucocorticoid suppressible mitogenic activity (denoted GSM). Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that GSM purified to near homogeneity migrated as a 28-kDa protein under nonreducing conditions and as a single 15-kDa polypeptide in the presence of sulfhydryl reducing agents suggesting a homodimeric structure. Anti-platelet-derived growth factor (PDGF) A-chain specific antibodies selectively immunodepleted the mitogenic activity which can be extracted from nonreducing gels in the 26-30-kDa fraction and, in Western blots, recognized the 15-kDa reduced form of GSM. Western blot analysis further showed that dexamethasone suppressed the level of secreted PDGF A-chain protein in BDS.1 cells but not in glucocorticoid receptor-deficient hepatoma cells. Northern blots revealed that dexamethasone reduced expression of the PDGF A-chain 2.3- and 1.7-kilobase transcripts in proportion to the level of detectable PDGF AA protein. Similarly to PDGF-AA, the hepatoma cell-derived GSM has a potent angiogenic activity. Taken together, our results demonstrate that the predominant glucocorticoid suppressible mitogen secreted from rat hepatoma cells is a PDGF A chain homodimer and suggest that in vivo glucocorticoids may potentially regulate hepatoma growth by modulating PDGF-stimulated tumor vascularization. PMID- 1917958 TI - Protein kinase C contains two phorbol ester binding domains. AB - A series of deletion and truncation mutants of protein kinase C (PKC) were expressed in the baculovirus-insect cell expression system in order to elucidate the ability of various domains of the enzyme to bind phorbol dibutyrate (PDBu). A PKC truncation mutant consisting of only the catalytic domain of the enzyme did not bind [3H]PDBu, whereas a PKC truncation mutant consisting of the regulatory domain (containing the tandem cysteine-rich putative zinc finger regions) bound [3H]PDBu. Deletion of the second conserved region (C2) of PKC did not abolish [3H]PDBu binding, whereas a deletion of the first conserved region (C1) of PKC, containing the two cysteine-rich sequences, completely abolished [3H]PDBu binding. Additional truncation and deletion mutants helped to localize the region necessary for [3H]PDBu binding; all PKC mutants that contained either one of the cysteine-rich zinc finger-like regions possessed phorbol ester binding activity. Scatchard analyses of these mutants indicated that each bound [3H]PDBu with equivalent affinity (21-41 nM); approximately 10-20-fold less than the native enzyme. In addition, a peptide of 146 amino acid residues from the first cysteine rich region, as well as a peptide of only 86 amino acids residues from the second cysteine-rich region, both bound [3H]PDBu with high affinity (31 +/- 4 and 59 +/- 13 nM, respectively). These data establish that PKC contains two phorbol ester binding domains which may function in its regulation. PMID- 1917959 TI - Transcriptional activity of the alpha 1(I)-collagen promoter is correlated with the formation of capillary-like structures by endothelial cells in vitro. AB - Bovine aortic endothelial (BAE) cells spontaneously form structures in vitro that resemble capillary-like cords or tubes. This process is associated with changes in the expression of certain extracellular matrix proteins that include type I collagen. BAE cells exhibiting angiogenesis in vitro were transfected with plasmids containing either chloramphenicol acetyltransferase or human growth hormone genes directed by promoter sequences from the human alpha 1(I)-collagen gene. Immunostaining for chloramphenicol acetyltransferase demonstrated that collagen promoter activity was restricted to cells involved in the formation of endothelial cords. In comparison to transfected monolayers of BAE cells, the transcriptional activity of the alpha 1(I)-collagen promoter increased by 7-fold in cultures undergoing angiogenesis in vitro. The selective ability of angiogenic endothelium to utilize the alpha 1(I)-collagen promoter is consistent with previous studies showing high levels of alpha 1(I)-collagen mRNA in BAE cells actively engaged in the formation of tubes (Iruela-Arispe, L., Hasselaar, P., and Sage, H. (1991) Lab. Invest. 64, 174-186). We conclude that transcriptional activation of the alpha 1(I)-collagen gene is closely linked to the morphologic alterations in cellular phenotype that accompany the transition of quiescent endothelial monolayers to the angiogenic state. PMID- 1917960 TI - Effects of endothelins on signal transduction and proliferation in human melanocytes. AB - We demonstrate here that human melanocytes could be regulated by endothelin (ET) derivatives, potent vasoconstrictive peptides synthesized by endothelial cells, to stimulate their proliferation and melanization via a receptor-mediated signal transduction pathway. Receptor-binding assay using [125I]ET indicated that unlabeled ET-1 or ET-2 competitively inhibited each binding of labeled ETs to melanocytes with a concentration for half-maximal inhibition (IC50) of 0.7 or 0.9 nM, respectively. The dissociation constant (Kd) and the number of sites of the specific bindings of ET-1 and those of ET-2 were almost the same (Kd: 1.81 nM, binding sites: 7.0-8.0 x 10(4) per cell). Upon incubation with cultured cells, the mass contents of inositol 1,4,5-trisphosphate and intracellular calcium level were substantially increased by 10 nM ET-1, ET-2, and ET-3, but not by big-ET with maximal response at 80-130-s postincubation. The addition of ET-1 and ET-2 at 1-50 nM concentrations caused human melanocytes to significantly stimulate DNA [( 3H]thymidine incorporation) and melanin synthesis (3H2O release and [14C] thiouracil incorporation). Furthermore, ETs exhibited an additive stimulatory effect on basic fibroblast growth factor-stimulated DNA synthesis. In a long-term serum-free culture system, the strongest stimulation of growth by 10 nM ET-1 or ET-2 was observed in the presence of 10 nM cholera toxin and 0.2% bovine pituitary extract, resulting in a 4.5-fold increase in cell number for 12 culture days. These findings strongly suggest involvement of ET in the mechanism regulating proliferation and melanization of human melanocytes. PMID- 1917962 TI - Recombination of exogenous interleukin 2 receptor gene flanked by immunoglobulin recombination signal sequences in a pre-B cell line and transgenic mice. AB - We have constructed a plasmid, pLTR100, which contains human interleukin 2 receptor light (IL-2R L) chain cDNA in the inverted orientation relative to the upstream SV40 promoter. The cDNA segment is flanked by the immunoglobulin gene recombination signal sequences so that the cDNA segment can invert and the human IL-2R L chain is subsequently expressed under the control of the SV40 promoter. A murine pre-B cell line, 38B9, transfected with pLTR100 began to express the human IL-2R L chain on the cell surface. The frequency of human IL-2R L chain positive cells increased almost linearly up to 50% for 60 days of culture after transfection. Southern blot analysis and sequencing of the DNA fragments at the recombination junction confirmed that the cDNA segment was inverted in a signal sequence-dependent manner by the variable-diversity-joining recombination process. Transgenic mice bearing the recombination substrate DNA similar to pLTR100 expressed the human IL-2 L chain in the spleen, thymus, and bone marrow, but not in the other tissues examined at the detectable level. Both IgM- and CD3 positive cells expressed the human IL-2R L chain, indicating that this artificial DNA can serve as a substrate for recombination both in B- and T-cells and that another DNA segment may be necessary to confer the cell-type specificity on the substrate DNA. PMID- 1917961 TI - Isolation, characterization, and structural organization of 10 formyltetrahydrofolate synthetase from spinach leaves. AB - One-carbon metabolism mediated by folate coenzymes plays an essential role in several major cellular processes. In the prokaryotes studied, three folate dependent enzymes, 10-formyltetrahydrofolate synthetase (EC 6.3.4.3), 5,10 methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9), and 5,10 methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5) generally exist as monofunctional or bifunctional proteins, whereas in eukaryotes the three activities are present on one polypeptide. The structural organization of these enzymes in plants had not previously been examined. We have purified the 10 formyltetrahydrofolate synthetase activity from spinach leaves to homogeneity and raised antibodies to it. The protein was a dimer with a subunit molecular weight of Mr = 67,000. The Km values for the three substrates, (6R)-tetrahydrofolate, ATP, and formate were 0.94, 0.043, and 21.9 mM, respectively. The enzyme required both monovalent and divalent cations for maximum activity. The 5,10 methylenetetrahydrofolate dehydrogenase and 5,10-methenyltetrahydrofolate cyclohydrolase activities of spinach coeluted separately from the 10 formyltetrahydrofolate synthetase activity on a Matrex Green-A column. On the same column, the activities of the yeast trifunctional C1-tetrahydrofolate synthase coeluted. In addition, antibodies raised to the purified spinach protein immunoinactivated and immunoprecipitated only the 10-formyltetrahydrofolate synthetase activity in a crude extract of spinach leaves. These results suggest that unlike the trifunctional form of C1-tetrahydrofolate synthase in the other eukaryotes examined, 10-formyltetrahydrofolate synthetase in spinach leaves is monofunctional and 5,10-methyl-enetetrahydrofolate dehydrogenase and 5,10 methenyltetrahydrofolate cyclohydrolase appear to be bifunctional. Although structurally dissimilar to the other eukaryotic trifunctional enzymes, the 35 amino-terminal residues of spinach 10-formyltetrahydrofolate synthetase showed 35% identity with six other tetrahydrofolate synthetases. PMID- 1917963 TI - Characterization of the CO oxidation/H2 evolution system of Rhodospirillum rubrum. Role of a 22-kDa iron-sulfur protein in mediating electron transfer between carbon monoxide dehydrogenase and hydrogenase. AB - The response of the membrane-associated carbon monoxide dehydrogenase (CODH) from Rhodospirillum rubrum to solubilization by detergents and organic solvents, the properties of solubilized CODH, and the mechanism for coupling CO oxidation to hydrogen evolution via a CO-induced hydrogenase activity have been investigated. The release of CODH by a variety of ionic and nonionic detergents occurs in a redox-dependent fashion: CODH is solubilized in the presence of low-potential reductants (dithionite, CO, and H2) but is resistant to solubilization from membranes prepared in the absence of reductant or membranes prepared in the presence of reductant and subsequently dye-oxidized. This redox-dependent response to detergent solubilization has been exploited to release CODH from the membranes in a purified state. CODH can also be solubilized from deoxycholate washed membranes in a redox-independent manner with 20% ethanol. CODH solubilized by deoxycholate or ethanol, when purified to homogeneity by the protocol previously described for heat-solubilized CODH (Bonam, D., and Ludden, P. W. (1987) J. Biol. Chem. 262, 2980-2987), is associated with a previously unobserved 22-kDa protein. The 22-kDa protein can be dissociated from CODH with acetonitrile and can be reconstituted with CODH, after removal of acetonitrile, in a stoichiometric (1:1) fashion. The isolated 22-kDa protein contained 4.0 iron atoms, a reducible Fe-S center, and was O2- and heat-labile. The 22-kDa protein did not alter the catalytic properties of CODH as assayed in vitro with methyl viologen as the electron acceptor for CO oxidation, but was required for reconstituting CO oxidation to hydrogen evolution via the CO-induced membrane bound hydrogenase. Other electron carrier proteins (ferredoxins and flavodoxin) were ineffective at coupling CO oxidation and hydrogen evolution. We conclude that the 22-kDa protein is a reversibly dissociable subunit of CODH tha mediates electron transfer to hydrogenase. PMID- 1917964 TI - The HA2 subunit of influenza hemagglutinin inserts into the target membrane prior to fusion. AB - The interaction between influenza virus and target membrane lipids during membrane fusion was studied with hydrophobic photoactivatable probes. Two probes, the newly synthesized bisphospholipid diphosphatidylethanolamine trifluoromethyl [3H]phenyl diazirine and the phospholipid analogue 1-palmitoyl-2(11-[4-[3 (trifluoromethyl)diazirinyl]phenyl]-[2-3H]- undecanoyl]-sn-glycero-3 phosphocholine (Harter, C., Bachi, T., Semenza, G., and Brunner , J. (1988) Biochemistry 27, 1856-1864), were used. Both labeled the HA2 subunit of the virus at low pH. By measuring virus-liposome interactions at 0 degrees C, it could be demonstrated that HA2 was inserted into the target membrane prior to fusion. As we have recently demonstrated, at this temperature, exposure of the fusion peptide of HA2 takes place within 15 s after acidification, but fusion does not start for 4 min (Stegmann, T., White, J. M., and Helenius, A. (1990) EMBO J. 9, 4231-4241). HA2 was labeled at least 2 min before fusion. No labeling of the HA1 subunit was seen. These data indicate that fusion is triggered by a direct interaction of the HA2 subunit of a kinetic intermediate form of HA with the lipids of the target membrane. Most likely, it is the fusion peptide of HA2 that is inserted into the target membrane. Just before fusion, HA is thus an integral membrane protein in both membranes. In contrast, the bromelain-derived ectodomain of HA was labeled by 1-palmitoyl-2(11-[4-[3-(trifluoromethyl)diazirinyl]phenyl]- [2-3H]undecanoyl)-sn-glycerol-3-phosphocholine at low pH but not by diphosphatidylethanolamine trifluoromethyl [3H]phenyl diazirine. This indicates that insertion of the fusion peptide of the bromelain-derived ectodomain of HA into a membrane differs from that of viral HA during fusion. PMID- 1917965 TI - Detection of cysteine conjugate metabolite adduct formation with specific mitochondrial proteins using antibodies raised against halothane metabolite adducts. AB - Antibodies raised against halothane metabolite adducts cross-react with S (1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC) and S-(2-chloro-1,1,2 trifluoroethyl)-L-cysteine metabolite adducts. Using these antibodies in immunohistochemical experiments, metabolite binding was localized to the damaged areas of the proximal tubule after treatment of male rats with TFEC. Immunoblot analysis of subcellular fractions of rat kidney tissue after in vivo treatment with TFEC revealed a high specificity for binding of metabolites to proteins of the mitochondrial fraction. These proteins may represent target molecules which play a role in cysteine conjugate induced nephrotoxicity. PMID- 1917966 TI - Carbohydrate-binding protein 35 (Mac-2), a laminin-binding lectin, forms functional dimers using cysteine 186. AB - Carbohydrate-binding protein 35 (CBP35), also known as the macrophage surface antigen Mac-2, is a lactosamine-specific lectin whose extracellular properties include the ability to agglutinate cells and to bind avidly to the basement membrane glycoprotein laminin. Although these and other properties would be facilitated by dimerization of this lectin, previous studies have argued against multimeric forms of this protein. We report here that macrophage CBP35, purified by laminin affinity chromatography, exists as several distinct species (Mr 35,000, 67,000, and 80,000) when analyzed under non-reducing conditions. This unexpected finding prompted us to study the biochemistry of multimerization using recombinant CBP35 (rCBP35). rCBP35 expressed in Escherichia coli forms disulfide linked homodimers (Mr 67,000). The dimeric form of CBP35 binds to laminin with higher affinity than does monomer and by a lactosamine-dependent mechanism. Site directed mutagenesis indicated that cysteine 186, the single cysteine residue in CBP35, is required for dimerization. These results raise the possibility that homo- and heterodimeric forms of CBP35 contribute to its postulated functions in cell-matrix interactions and growth regulation. PMID- 1917967 TI - Evidence for early induction of calmodulin gene expression in lymphocytes undergoing glucocorticoid-mediated apoptosis. AB - Glucocorticoid treatment of certain lymphoma cell lines and thymocytes activates a self-destructive pathway of programmed cell death referred to as apoptosis. Calcium and calmodulin (CaM) may be important signals in the apoptotic cascade because an early event is a sustained elevation in cytosolic Ca2+ and CaM inhibitors interfere with the death pathway. In the present study, expression of the CaM gene was examined during glucocorticoid-induced apoptosis in WEHI7.2 lymphocytes. Steady state levels of CaM mRNA were increased up to 10-fold following a 4-6-h exposure of WEHI7.2 cells to 10(-6) M dexamethasone. This increase was mediated through the glucocorticoid receptor since the response was not observed in WEHI7.418, a variant line which does not express active glucocorticoid receptor. Induction of CaM mRNA was dose-dependent and highly specific for glucocorticoids, as other steroids were unable to elicit the response. A stringent cell specificity was also observed. Pretreatment of WEHI7.2 lymphocytes with cycloheximide did not interfere with dexamethasone-dependent increases in CaM mRNA levels, and studies with actinomycin D demonstrated that the stability of the transcript was not altered by hormone, Finally, a calmodulin inhibitor elicited a protective effect on WEHI7.2 cells following glucocorticoid exposure. These results indicate that CaM mRNA levels were hormonally controlled in WEHI7.2 lymphocytes and support the putative involvement of CaM in glucocorticoid-induced apoptosis. PMID- 1917968 TI - Potato tuber type H phosphorylase isozyme. Molecular cloning, nucleotide sequence, and expression of a full-length cDNA in Escherichia coli. AB - Higher plant tissues contain two alpha-glucan phosphorylase isozymes (EC 2.4.1.1), types L and H, localized in the plastid and the cytoplasm, respectively. We already isolated and sequenced a cDNA clone encoding the type L isozyme. Presently, a cDNA clone encoding the type H counterpart was isolated from a cDNA library of immature potato tuber by plaque hybridization, using two oligonucleotide probes synthesized based on the partial amino acid sequences of the type H isozyme. The message encodes a polypeptide of 838 amino acid residues. Sequence comparison of the two potato tuber phosphorylase isozymes revealed two major distinctions; the type L isozyme contains a 78-residue insertion in the middle of the polypeptide chain as well as a 50-residue amino-terminal extension. Except for these extra portions, the two isozyme sequences show an identity of 63%. The entire structural gene for the type H isozyme was inserted 3'-downstream of the strong T7 RNA polymerase promoter in the expression plasmid pET-3b. Escherichia coli BL21 (DE3) cells carrying this plasmid produced active phosphorylase upon induction with isopropyl-beta-D-thiogalactoside at 22 degrees C. The expression is entirely dependent on the temperature; the bacteria did not produce a detectable amount of the active enzyme at 37 degrees C. Addition of pyridoxine to the culture medium was effective for the enzyme production. PMID- 1917969 TI - Role of peptide backbone conformation on biological activity of chemotactic peptides. AB - To investigate the role of peptide backbone conformation on the biological activity of chemotactic peptides, we synthesized a unique analog of N-formyl-Met Leu-Phe-OH incorporating the C alpha,alpha disubstituted residue, dipropylglycine (Dpg) in place of Leu. The conformation of the stereochemically constrained Dpg analog was examined in the crystalline state by x-ray diffraction and in solution using NMR, IR, and CD methods. The secretagogue activity of the peptide on human neutrophils was determined and compared with that of a stereochemically constrained, folded type II beta-turn analog incorporating 1 aminocyclohexanecarboxylic acid (Ac6c) at position 2 (f-Met-Ac6c-Phe-OMe), the parent peptide (f-Met-Leu-Phe-OH) and its methyl ester derivative (f-Met-Leu-Phe OMe). In the solid state, the Dpg analog adopts an extended beta-sheet-like structure with an intramolecular hydrogen bond between the NH and CO groups of the Dpg residue, thereby forming a fully extended (C5) conformation at position 2. The phi and psi values for Met and Phe residues are significantly lower than the values expected for an ideal antiparallel beta conformation causing a twist in the extended backbone both at the N and C termini. Nuclear magnetic resonance studies suggest the presence of a significant population of the peptide molecules in an extended antiparallel beta conformation and the involvement of Dpg NH in a C5 intramolecular hydrogen bond in solutions of deuterated chloroform and deuterated dimethyl sulfoxide. IR studies provide evidence for the presence of an intramolecular hydrogen bond in the molecule and the antiparallel extended conformation in chloroform solution. CD spectra in methanol, trifluoroethanol, and trimethyl phosphate indicate that the Dpg peptide shows slight conformational flexibility, whereas the folded Ac6c analog is quite rigid. The extended Dpg peptide consistently shows the highest activity in human peripheral blood neutrophils, being approximately 8 and 16 times more active than the parent peptide and the folded Ac6c analog, respectively. However, the finding that all four peptides have ED50 (the molar concentration of peptide to induce half maximal enzyme release) values in the 10(-8)-10(-9) M range suggests that an induced fit mechanism may indeed be important in this ligand-receptor interaction. Moreover, it is also possible that alterations in the backbone conformation at the tripeptide level may not significantly alter the side chain topography and/or the accessibility of key functional groups important for interaction with the receptor. PMID- 1917970 TI - Complete primary structure of a scallop striated muscle myosin heavy chain. Sequence comparison with other heavy chains reveals regions that might be critical for regulation. AB - We have determined the primary structure of the myosin heavy chain (MHC) of the striated adductor muscle of the scallop Aequipecten irradians by cloning and sequencing its cDNA. It is the first heavy chain sequence obtained in a directly Ca(2+)-regulated myosin. The 1938-amino acid sequence has an overall structure similar to other MHCs. The subfragment-1 region of the scallop MHC has a 59-62% sequence identity with sarcomeric and a 52-53% identity with nonsarcomeric (smooth and metazoan nonmuscle) MHCs. The heavy chain component of the regulatory domain (Kwon, H., Goodwin, E. B., Nyitray, L., Berliner, E., O'Neall-Hennessey, E., Melandri, F. D., and Szent-Gyorgyi, A. G. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 4771-4775) starts at either Leu-755 or Val-760. Ca(2+)-sensitive Trp residues (Wells, C., Warriner, K. E., and Bagshaw, C. R. (1985) Biochem. J. 231, 31-38) are located near the C-terminal end of this segment (residues 818-827). More detailed sequence comparison with other MHCs reveals that the 50-kDa domain and the N-terminal two-thirds of the 20-kDa domain differ substantially between sarcomeric and nonsarcomeric myosins. In contrast, in the light chain binding region of the regulatory domain (residues 784-844) the scallop sequence shows greater homology with regulated myosins (smooth muscle, nonmuscle, and invertebrate striated muscles) than with unregulated ones (vertebrate skeletal and heart muscles). The N-terminal 25-kDa domain also contains several residues which are preserved only in regulated myosins. These results indicate that certain heavy chain sites might be critical for regulation. The rod has features typical of sarcomeric myosins. It is 52-60% and 30-33% homologous with sarcomeric and nonsarcomeric MHCs, respectively. A Ser-rich tailpiece (residues 1918-1938) is apparently nonhelical. PMID- 1917971 TI - Developmental regulation of asparagine-linked oligosaccharide synthesis in Dictyostelium discoideum. AB - In the preceding report we demonstrated that the expression of two developmentally regulated alpha-mannosidase activities is induced in Dictyostelium discoideum during its differentiation from single-cell amoebae to multicellular organism (Sharkey, D. J., and Kornfeld, R. (1991) J. Biol. Chem. 266, 18477-18484). These activities, designated membrane alpha-mannosidase I (MI) and membrane alpha-mannosidase II (MII), were shown to have several properties in common with rat liver Golgi alpha-mannosidases I and II, respectively, suggesting that MI and MII may play a role in the processing of asparagine-linked oligosaccharides in developing D. discoideum. In this study we analyzed the structures of the asparagine-linked oligosaccharides synthesized by D. discoideum at various stages of development to determine the timing and extent of asparagine linked oligosaccharide processing. Cells were labeled with [2-3H] mannose, and then total cellular glycoproteins were digested with Pronase to generate glycopeptides that were fractionated on concanavalin A-Sepharose. Glycopeptides from each fraction were digested with endoglycosidase H, both before and after desulfation by solvolysis, and the released, neutral oligosaccharides were sized by high pressure liquid chromatography. At early stages of development, D. discoideum contain predominantly large high mannose-type oligosaccharides (Man9GlcNAc and Man8GlcNAc). Some of these are modified by GlcNAc residues attached beta 1-4 to the mannose-linked alpha 1-6 to the beta-linked core mannose (the "intersecting" position), as well as by fucose, sulfate, and phosphate. In contrast, the oligosaccharides found at late stages of development (18-24 h) have an array of sizes from Man9GlcNAc to Man3GlcNAc. These are still modified by GlcNAc, fucose, sulfate, and phosphate, but the percent of larger high mannose oligosaccharides that are modified with GlcNAc in the intersecting position decreases after 6 h of development, in parallel with the decrease in the intersecting GlcNAc transferase activity. Similarly, the changes in the size of asparagine-linked oligosaccharides synthesized during development correlate well with the appearance of MI and MII activities and suggest that these developmentally regulated alpha-mannosidase activities function in the processing of these oligosaccharides. This is supported further by the observation that oligosaccharide processing was inhibited in late stage cells labeled in the presence of either deoxymannojirimycin, an inhibitor of MI, or swainsonine, an inhibitor of MII. PMID- 1917972 TI - Amino acid residues necessary for putrescine stimulation of human S adenosylmethionine decarboxylase proenzyme processing and catalytic activity. AB - Human S-adenosylmethionine (AdoMet) decarboxylase is synthesized as a 38-kDa proenzyme that is autocatalytically cleaved, forming the covalently attached pyruvate cofactor and the two subunits (67 and 267 amino acid residues) of the mature enzyme. Both the cleavage reaction and the catalytic activity of the mature enzyme are stimulated by putrescine. Using site-specific mutagenesis and in vitro transcription followed by translation of the resultant RNA in a cellfree system, we have examined the importance of several amino acid residues on the processing reaction rate and catalytic activity and on stimulation of each of these by putrescine. Changing Cys82 to Ala decreased the stimulatory effect of putrescine on processing and completely eliminated catalytic activity, indicating a probable role in the active site of the enzyme, whereas changing Cys49 or Cys226 to Ala had minimal effects on processing and activity or the putrescine stimulation of either. Since Cys49 is the only cysteine residue in the smaller subunit, this indicates that disulfide-bond formation between the two subunits cannot be necessary for maintenance of the conformation for proenzyme processing or catalytic activity. Changing Glu8 or Glu11 to Gln produced an AdoMet decarboxylase that processed, but was catalytically inactive. Mutation at Glu11 also completely eliminated the putrescine stimulation of proenzyme processing, as did double mutation at Glu8 and Glu11, whereas the single mutation at Glu8 had no effect on the putrescine stimulation of proenzyme processing. Changing Glu15, Glu61, Glu67, Glu247, or Glu247 and Glu249 to Gln had a minimal effect on processing and activity or putrescine stimulation of either. These results demonstrate a role for the smaller subunit in the catalytic activity of the mature AdoMet decarboxylase enzyme and show that Glu8, Glu11, and Cys82 are essential for catalytic activity, with Glu11 also being essential for the putrescine stimulation of AdoMet decarboxylase proenzyme processing. PMID- 1917973 TI - A catalytic role for histidine 237 in rat mammary gland thioesterase II. AB - The involvement of a histidyl residue in the catalytic mechanism of thioesterase II, a serine active-site enzyme that catalyzes the chain terminating reaction in de novo fatty acid synthesis, has been inferred from studies with the inhibitor diethyl pyrocarbonate. Its likely location has been predicted by identification of conserved residues in related thioesterases and ultimately confirmed by site directed mutagenesis. Diethyl pyrocarbonate inactivated the enzyme with a second order rate constant of 49 M-1 s-1 at pH 6, 10 degrees C. Data analysis indicated that although several residues reacted with the reagent, modification of a single residue was responsible for the inactivation. Removal of a single ethoxycarbonyl moiety by treatment with neutral hydroxylamine completely restored enzyme activity. Prior ethoxycarbonylation of the histidyl residue blocked the ability of the active-site serine to react with phenylmethanesulfonyl fluoride. Comparison of the amino acid sequences of five structurally related proteins indicated that only 1 histidine has been completely conserved. Replacement of this residue in rat thioesterase II (His-237) with arginine and leucine by mutagenesis reduced the catalytic activity by 2-3 orders of magnitude. The activity of the mutant thioesterases, unlike that of the wild-type enzyme, was relatively insensitive to inhibition by diethyl pyrocarbonate and phenylmethylsulfonyl fluoride. These studies provide strong evidence that His-237 is involved directly in catalysis and suggest that its role is to increase the nucleophilic character of the active-site Ser-101 by acting as a proton acceptor thus facilitating acylation of the seryl residue. The mechanism appears to share certain common features with the charge-relay system characteristic of other esterases. PMID- 1917974 TI - Localization of the human complement component C3 binding site on the IgG heavy chain. AB - The location of the covalent binding site of the third component of complement (C3) on the IgG heavy chain was determined by sequence analysis of peptides generated by cyanogen bromide digestion of C3-IgG adducts. Activation of the alternative pathway by incubation of heat-aggregated human IgG1 with fresh normal human plasma formed covalent adducts of C3b-IgG. CNBr peptides of these adducts were transferred to a polyvinylidene difluoride membrane, and amino-terminal sequences were determined. A 40-kDa dipeptide containing the covalent bond was identified by labeling the free thiol group (generated during activation of the internal thioester of C3b) with iodo[1-14C]acetamide and analyzed by amino acid sequencing. The resulting double sequence suggested an adduct with NH2 termini at residue 938 (pro-C3 numbering) of C3 (75 residues NH2-terminal to the thioester) and residue 84 in the variable region of the IgG heavy chain. These results combined with results from hydroxylamine treatment (splits ester linkage between C3b and IgG) imply that this adduct peptide consists of a 22-kDa C3 fragment and an 18-kDa IgG fragment. Therefore, C3 binds covalently within the region extending from the last 20 residues of the variable region through the first 20 residues of CH2. PMID- 1917975 TI - Purification and functional characterization of MerD. A coregulator of the mercury resistance operon in gram-negative bacteria. AB - Mercury resistance operons (mer) from transposons Tn21, Tn501, and plasmid pDU1358 are highly homologous and inducible with Hg2+. The regulatory gene merR is transcribed from one promoter, which is divergently oriented from the promoter for the other mer genes. MerR, the product of the regulatory gene, negatively regulates its own expression as well as the expression of the other genes. MerR activates transcription of the operon in the presence of inducing concentrations of Hg2+. The most promoter distal gene, merD, which is cotranscribed with the structural genes, down regulates the mer operon. A frame-shift mutation in merD, created by deletion of 3 bp and an insertion of a 16 bp sequence upstream of the major inverted repeats present at the 3' end of the merD sequence, resulted in increased synthesis of the structural gene transcript and higher level of resistance to Hg2+ by a factor of about 2. MerD protein was over-produced using a T7 expression system. The overproduced protein was present in the pellet fraction, when cell lysates were centrifuged at a low speed. Approximately 80% pure MerD protein was recovered from the pellet fraction by extracting with a buffer solution containing 5 M urea. The purified protein migrated as a 13,500 molecular weight protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the N-terminal amino acid sequence corresponded to that deduced from the DNA sequence of merD. MerD bound specifically with the mer promoter sequence. DNase I footprinting experiments identified a common mer operator sequence for MerR and MerD. PMID- 1917976 TI - Analysis of unmodified endotoxin preparations by 252Cf plasma desorption mass spectrometry. Determination of molecular masses of the constituent native lipopolysaccharides. AB - Nine unmodified endotoxin preparations constituted of Re-, Rd-, and Rc-type lipopolysaccharides (2 to 5 glycoses), representing four species of enterobacteria were analyzed by 252Cf plasma desorption mass spectrometry. The constituent lipopolysaccharides were characterized by the ion pair: (M-H)- and its corresponding lipid fragment ion. The lipid fragment ion is produced by cleavage of the glycosidic bond of the 3-deoxy-D-manno-oct-2-ulosonic acid unit that substitutes O-6' of the glucosamin beta 1'-6glucosamine ("lipid A backbone") disaccharide of the lipid A moiety. These lipid fragment ions were identical to the (M-H)- ions seen in the spectra of homologous isolated lipid A preparations that were obtained by hydrolysis (pH 4.5, 100 degrees C) promoted by sodium dodecyl sulfate. Since the molecular components present in the endotoxin preparations analyzed are known, the ion pair (M-H)(-)-lipid fragment ion defines the molecular compositions of each individual lipopolysaccharide. Heterogeneity of the R-type endotoxin preparations analyzed was due almost exclusively to differing lipid A moieties. In three Salmonella minnesota 595 Re endotoxin preparations 10 different lipopolysaccharides were identified, only two of which were common to all three preparations. Of the nine lipopolysaccharides identified in two S. minnesota R7 endotoxin preparations, only two were present in both. PMID- 1917977 TI - Regulation of expression of the fatty acid synthase gene in 3T3-L1 cells by differentiation and triiodothyronine. AB - We have previously reported that fatty acid synthase mRNA levels increase 10-15 fold during the differentiation of 3T3-L1 cells to adipocytes, correlating well with the increase in the relative rate of synthesis for this enzyme. Here we show by transcription run-on assays that fatty acid synthase is highly transcribed in both preadipocytes and adipocytes. Furthermore, the transcription rate of the fatty acid synthase gene increased only 1.5-fold during the adipose conversion, whereas the apparent mRNA half-life increased from 2.5 h in preadipocytes to approximately 20 h in adipocytes. These results indicate that the increase in mRNA level during adipose conversion is not only due to the transcriptional activation of this gene but reflects the post-transcriptional stabilization of the message in adipocytes compared to preadipocytes. As thyroid hormone has been reported to increase lipogenic enzyme activities including fatty acid synthase in adipose tissue and in differentiating adipocytes in vitro, we used fully differentiated 3T3-L1 adipocytes to study T3 regulation of mammalian fatty acid synthase expression. We measured the effect of T3 on the relative rate of protein synthesis, mRNA content, and transcription rate of this gene. When mature adipocytes were treated with 10 nM T3, the relative rate of synthesis of fatty acid synthase increased 1.9-fold at 6 h, and it reached a maximum of 2.9-fold at 12 h. In addition, Northern blot analysis showed that T3 increased the steady state mRNA level for fatty acid synthase by 2.4-fold at 12 h and 4.5-fold at 24 h. Furthermore, run-on transcription analysis with isolated nuclei from cells treated with T3 showed that the transcription rate of the fatty acid synthase gene increased 4.1-fold after 6 h of T3 treatment and remained at the stimulated level for 24 h. These results demonstrate that the increase in transcription of the fatty acid synthase gene preceded that of the steady-state mRNA level, indicating that T3 regulates expression of fatty acid synthase primarily by modulating the transcription rate of the gene. In conclusion, while the differentiation-dependent increase in fatty acid synthase is mediated by both transcriptional and posttranscriptional processes, T3 regulation is primarily at the transcriptional level. PMID- 1917978 TI - An amino acid substitution in biobreeding rat corticosteroid binding globulin results in reduced steroid binding affinity. AB - BioBreeding (BB) rats are derived from an outbred colony of Wistar rats and are used as a model of autoimmune diabetes mellitus. A corticosteroid binding globulin (CBG) variant with reduced affinity for glucocorticoids has now been found in the blood of these animals. The dissociation rate constants of BB CBG for cortisol (4.42 nM) and corticosterone (1.43 nM) are both about 50% higher than those associated with Wistar CBG, but no obvious difference in the steroid binding specificity of BB and Wistar CBGs was detected. Purified BB and Wistar CBGs exhibit the same size heterogeneity when examined by polyacrylamide gel electrophoresis under denaturing conditions, and the sizes of their respective hepatic mRNAs are identical. The genetic basis for this abnormality was therefore determined by comparing the cDNA sequences for BB and Wistar CBG, and this revealed a point mutation that results in a single amino acid substitution at residue 276 (Ile in BB CBG and Met in Wistar CBG). To confirm that this mutation is responsible for the reduced steroid binding affinity associated with BB CBG, the cDNAs for rat CBG-Ile276 and CBG-Met276 were expressed in Chinese hamster ovary cells. The steroid binding affinities of the CBGs secreted by these cells were essentially identical with those observed in the corresponding serum samples from these two rat strains. The amino acid substitution identified in BB rat CBG therefore clearly accounts for the reduction in its steroid binding affinity, and further analysis of this and other natural CBG variants may reveal important information about the CBG steroid binding site. It is also possible that this mutation may contribute to the etiology of pathological abnormalities that are characteristic of the BB rat. PMID- 1917979 TI - Identification, purification, and characterization of a calcium-dependent endonuclease (NUC18) from apoptotic rat thymocytes. NUC18 is not histone H2B. AB - Glucocorticoids stimulate apoptosis in rat thymocytes that is characterized by internucleosomal DNA degradation. We have previously identified an 18-kDa calcium dependent nuclease whose activity is associated with this DNA degradation. The existence of this nuclease has been challenged by Alnemri and Litwack (1989) J. Biol. Chem. 264, 4104-4111, who suggest that the nuclease we observed was histone H2B. We report here a modified nuclease assay which uses [32P] DNA as a substrate that has enabled the purification and characterization of the 18-kDa nuclease (NUC18). Using Bio-Rex 70 chromatography in conjunction with this assay, we show that NUC18 can be separated from histone H2B. Enzymatically active NUC18, purified to apparent homogeneity, failed to react with two different anti-histone H2B antibodies. NUC18 was inactive in the absence of calcium and known inhibitors of apoptosis, i.e. zinc and aurintricarboxylic acid inhibit its activity. Although NUC18 activity was detected in nuclear extracts of thymocytes of both control and glucocorticoid-treated thymocytes, these activities were distinct. Gel filtration analysis revealed that NUC18 was present as a high molecular weight complex (greater than 100 kDa) in both groups of cells, whereas it also existed as a low molecular weight form in glucocorticoid-treated cells. Thus, NUC18 remains a candidate for the endonuclease responsible for the DNA degradation component of the apoptotic process. PMID- 1917980 TI - Brefeldin-A enhancement of ricin A-chain immunotoxins and blockade of intact ricin, modeccin, and abrin. AB - After binding, the protein toxins ricin, abrin, and modeccin are endocytosed and processed through the cell's vesicular system in a poorly understood fashion, prior to translocation to the cytosol. The role of the Golgi apparatus in toxin processing was studied using brefeldin-A (BFA), a fungal metabolite which blocks Golgi function. At concentrations that inhibit secretion of interleukin-2 (IL-2), BFA blocks ricin, modeccin, and abrin intoxication of a lymphocyte derived cell line (Jurkat). Paradoxically, BFA enhances the toxicity of two ricin A-chain immunotoxins targeted against distinct cell surface determinants. BFA concentrations which are optimal for immunotoxin enhancement are below those needed to affect ricin intoxication or IL-2 secretion. BFA blockade of ricin does not involve effects on ricin endocytosis, toxin translocation to the cytosol, or the enzymatic activity of toxin A-chain. In contrast, BFA has no effect on immunotoxin processing but does enhance the immunotoxin translocation step. It is concluded that: 1) intact Golgi function is required for holotoxin processing. 2) Intact Golgi function is not required for holotoxin translocation. 3) Golgi function is tightly linked to immunotoxin translocation. 4) BFA has effects on vesicular routing in addition to the block of Golgi function in secretion which has been reported. PMID- 1917981 TI - Rotation and interaction with epoxide hydrase of cytochrome P-450 in proteoliposomes. AB - Purified rat liver cytochrome P-450MC or P-450PB was co-reconstituted with epoxide hydrase in liposomal vesicles made of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine at a lipid to protein weight ratio of 5 by the cholate dialysis procedure. Rotational diffusion of the cytochromes was measured by observing the decay of absorption anisotropy, r(t), after photolysis of the heme.CO complex by a vertically polarized laser flash. Analysis of r(t) was based on a "rotation-about-membrane-normal" model. The measurements were used to investigate interactions of cytochrome P-450MC or P 450PB with epoxide hydrase. Different rotational mobilities of the two cytochromes were observed. The amount of mobile molecules was 78% for cytochrome P-450MC and 91% for P-450PB, and the rest was immobile within the experimental time range of 1 ms. In the presence of epoxide hydrase 85% of cytochrome P-450MC and 96% of P-450PB were mobile. Cross-linking of epoxide hydrase by anti-epoxide hydrase antibodies resulted in a drastic immobilization of the cytochromes, reducing the mobile population to 49% for P-450MC and to 60% for P-450PB. The rotational relaxation times phi of the mobile populations ranged from 210 to 283 microseconds. These results imply that both cytochromes P-450MC and P-450PB transiently associate with epoxide hydrase in liposomal membranes. Further analysis of the data showed that the angle between the heme plane of P-450MC and the membrane is 48 degrees or 62 degrees, different from the value of 55 degrees reported previously for P-450PB (Gut, J., Richter, C., Cherry, R. J., Winterhalter, K. H., and Kawato, S. (1983) J. Biol. Chem. 258, 8588-8594). PMID- 1917983 TI - Characterization of a novel A-active octaglycosylceramide with type 1 chain repeat inherited as a recessive trait in the epithelial cells of the small intestine of inbred rats. AB - Three strains of inbred rats, AVN, DA and LOU/M, were found to express human blood group A-active glycosphingolipids in the small intestine. Two A phenotypes were detected by immunostaining of thin layer chromatograms with monoclonal anti blood group A antibody. One phenotype (DA and LOU/M) displayed a novel glycolipid which was characterized as an A-active octaglycosylceramide with a type 1 chain repeat by methylation analysis, electron-impact mass spectrometry of the permethylated and permethylated LiAlH4-reduced molecule, and 1H NMR spectroscopy. It was designated A-8. GalNAc alpha 1-3Gal beta 1-(3GlcNAc beta 1-3Gal beta 1)2 4Glc beta 1-Cer 2 Fuc alpha 1 It is the first description of a type 1 chain repeat in a linear glycolipid. Calculation of minimum energy conformations showed that the orientations of the oligosaccharide chain and A determinant of A-8 differ from those of the homologous structure with a type 2 chain repeat present in human erythrocytes (Hakomori, S., Stellner, K., and Watanabe, K. (1972) Biochem. Biophys. Res. Commun. 49, 1061-1068). Genetic analysis demonstrated that A-8 is inherited as an autosomal recessive trait. PMID- 1917982 TI - Site-specific mutations in human ferredoxin that affect binding to ferredoxin reductase and cytochrome P450scc. AB - Ferredoxins found in animal mitochondria function in electron transfer from NADPH dependent ferredoxin reductase (Fd-reductase) to cytochrome P450 enzymes. To identify residues involved in binding of human ferredoxin to its electron transfer partners, neutral amino acids were introduced in a highly conserved acidic region (positions 68-86) by site-directed mutagenesis of the cDNA. Mutant ferredoxins were produced in Escherichia coli, and separate assays were used to determine the effect of substitutions on the capacity of each mutant to bind to Fd-reductase and cytochrome P450scc and to participate in the cholesterol side chain cleavage reaction. Replacements at several positions (mutants D68A, E74Q, and D86A) did not significantly affect activity, suggesting that acidic residues at these positions are not required for binding or electron transfer interactions. In contrast, substitutions at positions 76 and 79 (D76N and D79A) caused dramatic decreases in activity and in the affinity of ferredoxin for both Fd-reductase and P450scc; this suggests that the binding sites on ferredoxin for its redox partners overlap. Other substitutions (mutants D72A, D72N, E73A, E73Q, and D79N), however, caused differential effects on binding to Fd-reductase and P450scc, suggesting that the interaction sites are not identical. We propose a model in which Fd-reductase and P450scc share a requirement for ferredoxin residues Asp-76 and Asp-79 but have other determinants that differ and play an important role in binding. This model is consistent with the hypothesis that ferredoxin functions as a mobile shuttle in steroidogenic electron transfer, and it is considered unlikely that a functional ternary complex is formed. PMID- 1917984 TI - Modulation of neurite outgrowth in neuroblastoma cells by protein kinase C and platelet-activating factor. AB - Previous reports have shown that thrombin and activators of protein kinase C (PKC) inhibit neurite outgrowth (NOG) in neuroblastoma cells cultured in serum free medium. Therefore, we tested the hypothesis that PKC activation mediates the effect of thrombin on NOG in murine neuroblastoma NB-2a cells. After 2 h in serum free medium, 70% of the cells displayed neurites; addition of 300 ng/ml thrombin reduced NOG to 24% within 1 h. This inhibition was reduced after NB-2a cells were pretreated for 24 h with 200 nM phorbol dibutyrate down-regulate PKC. Thrombin and phorbol 12-myristate 13-acetate inhibited NOG in an additive way and the protein kinase inhibitors H-7, H-8, and HA1004 reversed the effect of thrombin on NOG with a rank order of activity consistent with PKC inhibition. Furthermore, PKC was translocated from the cytosol to a membrane-bound form 5 to 10 min after addition of thrombin. These findings indicate that thrombin inhibits NOG through a PKC-dependent pathway. Thrombin stimulates the synthesis of the phospholipid platelet-activating factor (PAF) in some cells. However, NOG was markedly stimulated when PAF or its analogue carbamyl-PAF were added to NB-2a cells in medium with serum. Furthermore, the PAF receptor antagonist SRI 63072 inhibited NOG in NB-2a cells in serum-free medium. These cells accumulated PAF with kinetics similar to that of NOG inducPAF was synthesized by the de novo pathway, as shown by the incorporation of [3H]choline. These findings suggest that PAF is a mediator of NOG in NB-2a cells. Thrombin neither stimulates nor inhibits PAF synthesis in these cells. PMID- 1917985 TI - Control of L-ornithine specificity in Escherichia coli ornithine transcarbamoylase. Site-directed mutagenic and pH studies. AB - Escherichia coli ornithine transcarbamoylase displays a strict specificity toward its second substrate L-ornithine. After forming a binary complex with carbamoyl phosphate and undergoing an induced-fit isomerization (Miller, A. W., and Kuo, L. C. (1990) J. Biol. Chem. 265, 15023-15027), the enzyme selects only the minor, zwitterionic ornithine with an uncharged delta-amino group for transcarbamoylation. Formation of the productive ternary complex is linked to two enzymic ionizations (pK alpha 6.2 approximately 6.3 and 9.1 approximately 9.3) and two ornithine ionizations (pK alpha 8.5 and 10.6) (Kuo, L. C., Herzberg, W., and Lipscomb, W. N. (1985) Biochemistry 24, 4754-4761). To elucidate the mechanism through which substrate specificity is achieved, the binding of L ornithine to two site-specific point mutants (Arg-57----Gly and Cys-273----Ala) of the enzyme has been examined. For the Gly-57 mutant enzyme, which does not undergo the induced-fit isomerization, affinity for ornithine drops by a factor of 500. The pH profile of the apparent equilibrium constant governing the association of L-ornithine to the binary complex of this mutant reveals that only two enzymic ionizations affect ornithine binding. The ionizations linked to L ornithine are not detected. Hence, the preisomerized binary complex binds not only poorly but also indiscriminately all ionic species of L-ornithine. For the Ala-273 mutant enzyme, which exhibits the induced-fit isomerization, affinity of the amino acid is decreased by an order of magnitude. Ionizations of L-ornithine to yield a zwitterion for binding are detected in pH analyses for this mutant, but the pK alpha of 6.2 associated with the enzymic deprotonation in the wild type is absent. Therefore, Cys-273 is a binding site of L-ornithine. The D-isomer of ornithine is a very weak, deadend ligand to all three forms of the enzyme with affinities in the millimolar range. Employing the estimated affinities of D- and L-ornithine, the binding stereospecificity of the wild-type and mutant binary complexes toward the amino acid substrate may be evaluated. L-Ornithine binds preferentially over D-ornithine by two and four orders of magnitude in the absence and presence of protein isomerization, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1917986 TI - Relationship between agonist- and thapsigargin-sensitive calcium pools in adrenal glomerulosa cells. Thapsigargin-induced Ca2+ mobilization and entry. AB - The relationships between agonist-sensitive calcium pools and those discharged by the Ca(2+)-ATPase inhibitor thapsigargin were studied in intact bovine adrenal glomerulosa cells and a subcellular adrenocortical membrane fraction. In Fura-2 loaded glomerulosa cells, angiotensin II (AII) stimulated a rapid increase in cytoplasmic Ca2+ concentration ([Ca2+]i) followed by a smaller plateau phase that was dependent on extra-cellular Ca2+. In such cells thapsigargin caused a sustained and dose-dependent increase in [Ca2+]i which was diminished in Ca(2+) deficient medium. The contribution of an influx component to the thapsigargin induced [Ca2+]i response was demonstrated by measurement of 45Ca influx rate in glomerulosa cells. Thapsigargin-induced Ca2+ entry was significantly less than that evoked by AII, and its kinetics were similar to those of the concomitant increase in [Ca2+]i. The rate of emptying of the agonist-responsive Ca2+ pool after thapsigargin treatment, as indicated by the progressive decrease in the size of the AII-induced Ca2+ transient, showed a rapid initial (t1/2 = 1.7 min) component that accounted for about 80% of the response and a slowly decreasing phase with t1/2 = 112 min. The latter thapsigargin-resistant component was abolished by the removal of extracellular Ca2+. Pretreatment with AII dose dependently attenuated but did not abolish the subsequent Ca2+ response to thapsigargin and also increased the rate of the Ca2+ rise induced by thapsigargin. In bovine adrenocortical microsomes, thapsigargin inhibited the ATP dependent filling of Ca2+ pools and caused a dose-dependent rise in extravesicular Ca2+ levels when added to previously loaded microsomes. The thapsigargin-releasable Ca2+ pool in adrenal microsomes was larger than the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-sensitive Ca2+ pool but only slightly greater than the GTP-releasable pool. Ins(1,4,5)P3-induced Ca2+ release was reduced markedly when ATP-dependent Ca2+ loading of the microsomes was prevented by prior addition of thapsigargin. However, the subsequent Ca2+ response to Ins(1,4,5)P3 was consistently better preserved after the addition of thapsigargin to microsomes preloaded with Ca2+. This difference suggests that although Ca2+ uptake by the Ins(1,4,5)P3-responsive pool is also sensitive to thapsigargin, once filled, this pool shows a slower passive leakage than other thapsigargin sensitive pools. These findings indicate that thapsigargin increases [Ca2+]i by inhibiting Ca2+ uptake into multiple intracellular Ca2+ pools and by also promoting entry of extracellular Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1917987 TI - Replacement of lysine 269 by arginine in Escherichia coli tryptophan indole-lyase affects the formation and breakdown of quinonoid complexes. AB - Lysine 269 in Escherichia coli tryptophan indole-lyase (tryptophanase) has been changed to arginine by site-directed mutagenesis. The resultant K269R mutant enzyme exhibits kcat values about 10% those of the wild-type enzyme with S-(o nitrophenyl)-L-cysteine, L-tryptophan, and S-benzyl-L-cysteine, while kcat/Km values are reduced to 2% or less. The pH profile of kcat/Km for S-benzyl-L cysteine for the mutant enzyme exhibits two pK alpha values which are too close to separate, with an average value of 7.6, while the wild-type enzyme exhibits pK alpha values of 6.0 and 7.8. The pK alpha for the interconversion of the 335 and 412 nm forms of the K269R enzyme is 8.3, while the wild-type enzyme exhibits a pK alpha of 7.4. Steady-state kinetic isotope effects on the reaction of [alpha-2H]S benzyl-L-cysteine with the K269R mutant enzyme (Dkcat = 2.0; D(kcat/Km) = 3.9) are larger than those of the wild-type enzyme (Dkcat = 1.4; D(kcat/Km) = 2.9). Rapid scanning stopped-flow kinetic studies demonstrate that the K269R mutant enzyme does not accumulate quinonoid intermediates with L-alanine, L-tryptophan, or S-methyl-L-cysteine, but does form quinonoid absorption peaks in complexes with S-benzyl-L-cysteine and oxidolyl-L-alanine, whereas wild-type enzyme forms prominent quinonoid bands with all these amino acids. Single wavelength stopped flow kinetic studies demonstrate that the alpha-deprotonation of S-benzyl-L cysteine is 6-fold slower in the K269R mutant enzyme, while the intrinsic deuterium kinetic isotope effect is less for the K269R enzyme (Dk = 4.2) than for the wild-type (Dk = 7.9). The decay of the K269R quinonoid intermediate in the presence of benzimidazole is 7.1-fold slower than that of the wild-type enzyme. These results demonstrate that Lys-269 plays a significant role in the conformational changes or electrostatic effects obligatory to the formation and decomposition of the quinonoid intermediate, although it is not an essential basic residue. PMID- 1917989 TI - The molecular structure of the high potential iron-sulfur protein isolated from Ectothiorhodospira halophila determined at 2.5-A resolution. AB - The molecular structure of a high potential iron-sulfur protein (HiPIP) isolated from the purple photosynthetic bacterium, Ectothiorhodospira halophila strain BN9626, has been solved by x-ray diffraction analysis to a nominal resolution of 2.5 A and refined to a crystallographic R value of 18.4% including all measured x ray data from 30.0- to 2.5-A resolution. Crystals used in the investigation contained two molecules/asymmetric unit and belonged to the space group P21 with unit cell dimensions of a = 60.00 A, b = 31.94 A, c = 40.27 A, and beta = 100.5 degrees. An interpretable electron density map, obtained by combining x-ray data from one isomorphous heavy atom derivative with non-crystallographic symmetry averaging and solvent flattening, clearly showed that this high potential iron sulfur protein contains 71 amino acid residues, rather than 70 as originally reported. As in other bacterial ferredoxins, the [4Fe-4S] cluster adopts a cubane like conformation and is ligated to the protein via four cysteinyl sulfur ligands. The overall secondary structure of the E. halophila HiPIP is characterized by a series of Type I and Type II turns allowing the polypeptide chain to wrap around the [4Fe-4S] prosthetic group. The hydrogen bonding pattern around the cluster is nearly identical to that originally observed in the 85 amino acid residue Chromatium vinosum HiPIP and consequently, the 240 mV difference in redox potentials between these two proteins cannot be simply attributed to hydrogen bonding patterns alone. PMID- 1917988 TI - Phosphorylated rhodopsin and heparin induce similar conformational changes in arrestin. AB - Photoactivated rhodopsin is quenched upon its phosphorylation in the reaction catalyzed by rhodopsin kinase and the subsequent binding of a regulatory protein, arrestin. We have found that heparin and other polyanions compete with photoactivated, phosphorylated rhodopsin to bind arrestin (48-kDa protein, S antigen). This is shown (a) by the suppression of stabilized metarhodopsin II; (b) by changes in the digestion of arrestin in the presence of heparin; and (c) by the restoration of arrestin-quenched phosphodiesterase activity. When bound to arrestin, heparin also mimics phosphorylated rhodopsin by similarly exposing arrestin to limited proteolysis. We conclude that heparin and rhodopsin have similar means of binding to arrestin, and we propose a cationic region of arrestin (beginning with Lys163 of the bovine sequence) as the interaction site. In agreement with previous kinetic data we interpret the results in terms of a binding conformation of arrestin which is stabilized by rhodopsin or heparin and is open to proteolytic attack. PMID- 1917990 TI - Purification, characterization, and partial sequence analysis of a newly identified EF-hand type 13-kDa Ca(2+)-binding protein from smooth muscle and non muscle tissues. AB - A novel Ca(2+)-binding protein, tentatively designated calgizzarin, has been purified to apparent homogeneity from chicken gizzard smooth muscle by W-7 (N-(6 aminohexyl-5-chloro-1-naphthalenesulfonamide))-Sepharose affinity chromatography and ion-exchange chromatography. Application of W-7-Sepharose affinity chromatography to various tissues revealed that calgizzarin-like proteins were abundant in bovine aorta and rabbit lung. Using the same procedure, we could purify a calgizzarin-like protein from rabbit lung. Calgizzarin has a Mr of 13,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and approximately 30,000 as determined by gel filtration on a TSK G 3000SW high performance liquid chromatography column, suggesting that calgizzarin seems to be a rodlike protein. The isoelectric point of calgizzarin was found to be pH 5.8. Calgizzarin can exist as a dimer by forming a disulfide bridge. The 45Ca autoradiographic technique showed that the protein binds to Ca2+. On an alkaline/urea gel, calgizzarin migrated faster in the presence of EGTA than in the presence of CaCl2, thereby indicating a Ca(2+)-dependent conformational change in this protein. The partial amino acid sequence (65 amino acid residues) of calgizzarin was seen to be SLLAVFQRYAGREGDNLKLSKKEFRTFMNTELASFTKNQKDPAVVDRMMKRLDINSDGQLDFQEF, and two putative Ca(2+)-binding sites (GREGDNLKLSKKE and D INSDGQLDFQE) were detected. So far as the obtained 65-amino acid sequence is concerned, calgizzarin has approximately a 50% sequence homology with S-100 alpha, 47% with S-100 beta, and 39% with pEL-98 protein. PMID- 1917991 TI - The retinylidene Schiff base counterion in bacteriorhodopsin. AB - Previous studies of bacteriorhodopsin have indicated interactions between Asp-85, Asp-212, Arg-82, and the retinylidene Schiff base. The counterion environment of the Schiff base has now been further investigated by using single and double mutants of the above amino acids. Chromophore regeneration from bacterioopsin proceeds to a normal extent in the presence of a single aspartate or glutamate residue at position 85 or 212, whereas replacement of both charged amino acids in the mutant Asp-85----Asn/Asp-212----Asn abolishes the binding of retinal. This indicates that a carboxylate group at either residue 85 or 212 is required as counterion for formation and for stabilization of the protonated Schiff base. Measurements of the pKa of the Schiff base reveal reductions of greater than 3.5 units for neutral single mutants of Asp-85 but only decreases of less than 1.2 units for corresponding substitutions of Asp-212, relative to the wild type. Substitutions of Asp-85 show large red shifts in the absorption spectrum that are partially reversible upon addition of anions, whereas mutants of Asp-212 display minor red shifts or blue shifts. We conclude, therefore, that Asp-85 is the retinylidene Schiff base counterion in wild-type bacteriorhodopsin. In the mutant Asp-85----Asn/Asp-212----Asn formation of a protonated Schiff base chromophore is restored in the presence of salts. The spectral properties of the double mutant are similar to those of the acid-purple form of bacteriorhodopsin. Upon addition of salts the folded structure of wild-type and mutant proteins can be stabilized at low pH in lipid/detergent micelles. The data indicate that exogenous anions serve as surrogate counterions to the protonated Schiff base, when the intrinsic counterions have been neutralized by mutation or by protonation. PMID- 1917992 TI - Oxidation of deuterated compounds by high specific activity methane monooxygenase from Methylosinus trichosporium. Mechanistic implications. AB - Hydrocarbon oxidations catalyzed by methane monooxygenase purified to high specific activity from the type II methanotroph Methylosinus trichosporium OB3b were compared to the same reactions catalyzed by methane monooxygenase from the type I methanotroph Methylococcus capsulatus Bath and liver microsomal cytochrome P-450. The two methane monooxygenases produced nearly identical product distributions, in accord with physical studies of the enzymes which have shown them to be very similar. The products obtained from the oxidation of a series of deuterated substrates by the M. trichosporium methane monooxygenase were very similar to those reported for the same reaction catalyzed by liver microsomal cytochrome P-450, suggesting that the enzymes use similar mechanisms. However, differences in the product distributions and other aspects of the reactions indicated the mechanisms are not identical. Methane monooxygenase epoxidized propene in D2O and d6-propene in H2O without exchange of substrate protons or deuterons with solvent, in contrast to cytochrome P-450 (Groves, J. T., Avaria Neisser, G. E., Fish, K. M., Imachi, M., and Kuczkowski, R. L. (1986) J. Am. Chem. Soc. 108, 3837-3838), suggesting that the mechanism of epoxidation of olefins by methane monooxygenase differs at least in part from that of cytochrome P-450. Hydroxylation of alkanes by methane monooxygenase revealed close similarities to hydroxylations by cytochrome P-450. Allylic hydroxylation of 3,3,6,6-d4-cyclohexene occurred with approximately 20% allylic rearrangement in the case of methane monooxygenase, whereas 33% was reported for this reaction catalyzed by cytochrome P-450 (Groves, J. T., and Subramanian, D. V. (1984) J. Am. Chem. Soc. 106, 2177-2181). Similarly, hydroxylation of exo,exo,exo,exo 2,3,5,6-d4-norbornane by methane monooxygenase occurred with epimerization, but to a lesser extent than reported for cytochrome P-450 (Groves, J. T., McClusky, G. A., White, R. E., and Coon, M. J. (1978) Biochem. Biophys. Res. Commun. 81, 154-160). A large intramolecular isotope effect, kH,exo/kD,exo greater than or equal to 5.5, was calculated for this reaction. However, the intermolecular kinetic isotope effect on Vm for methane oxidation was small, suggesting that steps other than C-H bond breakage were rate limiting in the overall enzymatic reaction. Similar isotope effects have been observed for cytochrome P-450. These observations indicate a stepwise mechanism of hydroxylation for methane monooxygenase analogous to that proposed for cytochrome P-450.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1917993 TI - Conversion of 1-O-[3H]alkyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine to lyso platelet-activating factor by the CoA-independent transacylase in membrane fractions of human neutrophils. AB - The first step in the synthesis of platelet-activating factor (PAF) in stimulated neutrophils is generally accepted to be hydrolysis of 1-O-alkyl-2-acyl-sn-glycero 3-phosphorylcholine (1-O-alkyl-2-acyl-GPC), with 1-O-alkyl-2-arachidonoyl-GPC being the preferred precursor. Characterization of the enzymatic activity responsible for the hydrolysis of 1-O-alkyl-2-arachidonoyl-GPC has been hampered by lack of an active and reliable cell-free system for study. In the present studies, membrane preparations containing 1-O-[3H]alkyl-2-arachidonoyl-GPC were prepared from intact human neutrophils that had been labeled using 1-O [3H]hexadecyl-2-lyso-GPC. When the labeled membrane preparations were incubated in the presence of unlabeled 1-O-alkyl-2-lyso-GPC (5 microM), rapid deacylation (up to 25% of the label in 10 min) of the 1-O-[3H]alkyl-2-arachidonoyl-GPC to 1-O [3H]alkyl-2-lyso-GPC (lyso-PAF) was observed. The deacylation activity appeared to be the same in preparations from resting or stimulated cells. No requirement for Ca2+, various nucleotides, or protein kinase activation could be demonstrated. A number of observations indicated that [3H]lyso-PAF is formed in the system by the action of the CoA-independent transacylase present in the cells rather than by phospholipase A2. Both 1-O-alkyl-2-lyso-GPC and 1-acyl-2-lyso-GPC elicited deacylation of 1-O-[3H]alkyl-2-arachidonoyl-GPC, whereas neither 3-O alkyl-2-lyso-GPC nor 1-O-alkyl-2-O-methyl-rac-glycero-3-phosphorylcholine, which should act as detergents but are not transacylase substrates, effected deacylation. The deacylation activity and CoA-independent transacylase activities were blocked in parallel by a number of inhibitors and by heat inactivation. In preparations containing 1-O-alkyl-2-[3H]arachidonoyl-GPC, no release of free [3H]arachidonic acid was observed. However, a shift of the [3H]arachidonate into exogenous 1-O-tetradecyl-2-lyso-GPC was observed in the system. These findings are consistent with the generation of [3H]lyso-PAF by the CoA-independent transacylase activity. PMID- 1917994 TI - Evidence that hydrolysis of ethanolamine plasmalogens triggers synthesis of platelet-activating factor via a transacylation reaction. AB - Addition of 1-O-alk-1'-enyl-2-lyso-sn-glycero-3-phosphoethanolamine (alkenyl-lyso GPE) to human neutrophil membrane preparations containing 1-O-[3H]hexadecyl-2 arachidonoyl-sn-glycero-3-phosphorylcholine (1-O-[3H]alkyl-2-arachidonoyl-GPC) resulted in rapid deacylation of the 1-O-[3H]alkyl-2-arachidonoyl-GPC to 1-O [3H]alkyl-2-lyso-GPC (lyso-platelet-activating factor, lyso-PAF). When acetyl-CoA was included in the incubation mixture, the [3H]lyso-PAF was converted to [3H]PAF. Studies of [3H]arachidonate-labeled neutrophils permeabilized with Staphlococcus aureus alpha-toxin revealed a major shift of labeled [3H]arachidonate from the choline to the ethanolamine-containing phosphoglycerides upon addition of alkenyl-lyso-GPE. The studies indicated that lyso-PAF is formed in the system by the transfer of arachidonate from 1-O-alkyl-2 arachidonoyl-GPC to the alkenyl-lyso-GPE by a CoA-independent transacylase reaction. Mass measurements revealed a rapid loss of arachidonate from 1-radyl-2 acyl-GPE and a concomitant increase in alkenyl-lyso-GPE upon stimulation of the neutrophils by ionophore A23187. Based on these and other findings, a pathway is proposed that may play a significant, if not obligatory, role in the synthesis of PAF in intact stimulated neutrophils. It has been widely accepted that phospholipase A2 acts directly on 1-O-alkyl-2-arachidonoyl-GPC as the first step in the synthesis of PAF via formation of lyso-PAF. In the proposed scheme, phospholipase A2, upon stimulation, acts rapidly on ethanolamine plasmalogen selectively releasing arachidonic acid and generating alkenyl-lyso-GPE. The CoA independent transacylase then selectively transfers arachidonate from 1-radyl-2 arachidonoyl-GPC to the alkenyl-lyso-GPE generating lyso-PAF, which is then acetylated to form PAF. The interactions outlined can account for the synthesis of 1-acyl-2-acetyl-GPC, 1-O-alk-1'-enyl-2-acetyl-GPE, and eicosanoids, in parallel with PAF. PMID- 1917995 TI - Membrane-mediated assembly of the prothrombinase complex. AB - Prothrombinase assembly was studied on macroscopic planar bilayers consisting of 20% dioleoyl-phosphatidylserine (DOPS) and 80% dioleoyl-phosphatidylcholine (DOPC). The dissociation constant for the binding of factor Xa to the bilayer, measured by ellipsometry, was Kd = 47 +/- 8 nM (mean +/- S.D.) and this value was lowered to Kd = 2.2 +/- 0.3 pM by preadsorption of factor Va. This latter value was determined from direct measurement of steady-state thrombin production. A comparable value of Kd = 1.0 +/- 0.1 pM was found by repeating these experiments in suspensions of phospholipid vesicles, and it was verified that prothrombinase assembly was not influenced by the addition of prothrombin. Using a minute amount (0.094 fmol cm-2) of preadsorbed factor Va, it was found that the rate of prothrombinase assembly exceeds the rate of collisions between Xa molecules from the buffer and the sparse Va molecules on the bilayer. Apparently, factor Xa adsorbs first to the membrane and then associates rapidly with factor Va by lateral diffusion. The data indicate almost instantaneous equilibrium of this complex formation on the surface with a lower limit for the bimolecular rate constant of kon = 2.8 x 10(13) (mol/cm2)-1 s-1. In suspensions of small phospholipid vesicles, prothrombinase assembly is collisionally limited and the value of kon should be proportional to vesicle diameter. This was verified with a method for estimation of kon values from thrombin generation curves. Values of 0.36 x 10(9) and 1.6 x 10(9) M-1 s-1 were found for vesicles of 20-30- and 60-80 nm diameter, respectively. PMID- 1917996 TI - Mac-2-binding glycoproteins. Putative ligands for a cytosolic beta-galactoside lectin. AB - Mac-2, a galactose-binding lectin secretion by activated macrophages, is the major non-integrin laminin-binding protein in these cells. Mac-2 is also expressed by epithelial cells in the intestine and kidney. We wished to identify intestinal glycoproteins other than laminin that have a high affinity for Mac-2 and that could be considered as candidate ligands or partners for this lectin in intestinal epithelium. Certain lines of human colon adenocarcinoma cells produce two Mac-2-binding glycoproteins (M2BP-1 and M2BP-2) that were identified by their avid association with Mac-2 following detergent lysis and immunoprecipitation. These glycoproteins do not share a common epitope with Mac-2, and the interaction between Mac-2 and these proteins is mediated through the carbohydrate-binding domain of Mac-2 and sugar moieties on M2BP-1 and M2BP-2. M2BP-1 (98 kDa) and M2BP 2 (70 kDa) were purified by immunoaffinity chromatography and were specifically eluted with either galactose or lactose. Peptide maps revealed that M2BP-1 and M2BP-2 are structurally related. M2BP-1 is secreted and could conceivably associate with Mac-2 extracellularly. N-terminal sequence analysis of M2BP-2 suggests that these glycoproteins represent a unique subset of candidate ligands for this mammalian beta-galactoside lectin. PMID- 1917997 TI - Histone acetylation in Zea mays.I. Activities of histone acetyltransferases and histone deacetylases. AB - DEAE-Sepharose chromatography of extracts from Zea mays meristematic cells revealed multiple histone acetyltransferase and histone deacetylase enzyme forms. An improved method for nuclear isolation allowed us to discriminate nuclear and cytoplasmic enzymes. Two nuclear histone acetyltransferases, A1 and A2, a cytoplasmic B-enzyme and two nuclear histone deacetylases, HD1 and HD2, have been identified. The histone specificity of the different enzyme forms has been studied in an in vitro system, using chicken erythrocyte histones as substrate. The cytoplasmic histone acetyltransferase B is the predominant enzyme, which acetylates mainly histone H4 and to a lesser extent H2A. The nuclear histone acetyltransferase A1 preferentially acetylates H3 and also H4, whereas enzyme A2 is specific for H3. This substrate specificity was confirmed with homologous Z. mays histones. The two histone deacetylases differ from each other with respect to ionic strength dependence, inhibition by acetate and butyrate, and substrate specificity. The strong inhibitory effect of acetate on histone deacetylases was exploited to distinguish different histone acetyltransferase forms. PMID- 1917998 TI - Histone acetylation in Zea mays. II. Biological significance of post translational histone acetylation during embryo germination. AB - Multiple forms of histone acetyltransferases and histone deacetylases, which have been separated and characterized in the accompanying manuscript (Lopez-Rodas, G., Georgieva, E. I., Sendra, R., and Loidl, P. (1991) J. Biol. Chem. 266, 18745 18750), together with in vivo acetate incorporation, were studied during the germination of Zea mays embryos. Total histone acetyltransferase activity increases during germination with two maxima at 40 and 72 h after start of germination. This fluctuation is mainly due to the cytoplasmic B-enzyme which predominantly acetylates histone H4 up to the diacetylated form. The nuclear histone acetyltransferase A2, specific for H3, is low throughout germination, except at 24 h, when it transiently becomes the main activity. Both enzymes are also present in the dry embryo, whereas the second nuclear enzyme A1, specific for H3 and H4, is absent in the initial stage of differentiation. The two histone deacetylases, HD1 and HD2, exhibit entirely different patterns. Whereas HD1 activity is low in the dry embryo and increases during germination, HD2 is the predominant enzyme at the start of differentiation, but almost disappears at later stages. Analysis of the in vivo acetate incorporation reveals that H4 is present in up to tetraacetylated subspecies. The pattern of acetate incorporation into core histones closely resembles the fluctuations of histone acetyltransferase B. Based on the analysis of thymidine kinase activity a close correlation was established between histone acetyltransferase B and DNA replication, whereas the A2 enzyme is associated with transcriptional activity. Histone deacetylase HD1 obviously serves a specific function in the dry embryo and could be a prerequisite for DNA repair processes. The study confirms the idea of DNA repair processes. The study confirms the idea of multiple functions of histone acetylation and assigns distinct enzymes, involved in this modification, to certain nuclear processes. PMID- 1917999 TI - Structural aspects of the human C5 gene. Intron/exon organization, 5'-flanking region features, and characterization of two truncated cDNA clones. AB - Human C5 cDNA fragments were used to identify five overlapping cosmid clones that spanned the entire C5 gene. Partial sequencing and Southern analysis of the clones were performed to identify intron/exon boundaries and to map intron size. The human C5 gene is 79 kilobases in length and is comprised of 41 exons. Comparison of C5 with the homologous family members C3 and C4 revealed striking similarities in exon size and number. Less, although significant similarities were also observed with the family member alpha 2-macroglobulin. The transcriptional start site for the C5 gene was observed as a doublet at positions 29 and 28 nucleotides upstream of the ATG start codon. The 5'-flanking region of the gene contains sequences homologous with several known responsive elements, including interferon, interleukin-6, glucocorticoid, estrogen, NF-kappa B, and HNF-1. Two previously identified truncated cDNAs, pHC5A and pHC5B, contain 21 and 16 exons, respectively. The last exon in pHC5A, designated exon 21a, is a product of alternative splicing and is not present in the major full-length transcript. Truncation of pHC5A is the result of an alternative polyadenylation signal located in exon 21a. In pHC5B, exon 16 is extended on the 3' end by additional flanking genomic sequence that also contains an alternative polyadenylation signal. PMID- 1918001 TI - Immobilized insulin for high capacity affinity chromatography of insulin receptors. AB - Insulin receptors can be purified by affinity chromatography on immobilized insulin, but published methods all suffer from a rather low capacity of the affinity columns. By using insulin that has been protected in positions A1 and B29, we have been able to couple the insulin selectively through the B1 amino group to divinyl sulfone-activated agarose. The N terminus of the B-chain is the most innocuous site as far as receptor-insulin interaction is concerned, and this strategy allowed us to make affinity columns with capacities of several milligrams of receptor/ml of resin. The receptor used was the soluble ectodomain of the human insulin receptor, produced in transfected baby hamster kidney cells. The column preparation and the elution conditions are described in detail, as the efficacy of the purification depends strongly on both. The purity of the eluted receptors was so high that quantitative amino acid analysis fitted with theory. The molar absorption coefficient at 278.5 nm was 296,000 M-1 cm-1. Finally, it could be unequivocally established that the soluble receptor binds two molecules of insulin with equal affinity. PMID- 1918000 TI - Isolation, characterization, and in vitro expression of a cDNA that encodes the kidney isoenzyme of the mitochondrial glutaminase. AB - A cDNA that encodes the kidney isoenzyme of the mitochondrial glutaminase (pGA) was generated by recombination of two cDNAs that were isolated from a random primed rat brain lambda gt11 library. pGA encodes 674 amino acids which includes an N-terminal sequence of 16 residues that should form an amphipathic helix, typical of a mitochondrial targeting sequence. Residues 73-90 correspond to the N terminal sequence of the more abundant 65-kDa glutaminase peptide. In vitro transcription and translation of pGA yields a 72-kDa peptide that is immunoprecipitated with glutaminase-specific antibodies. Incubation of the glutaminase precursor with isolated mitochondria yields the 68- and 65-kDa peptides that are characteristic of the mature glutaminase. Thus, the two mature glutaminase peptides are synthesized from a single precursor. The complete 3' nontranslated region of the GA mRNA was characterized by sequencing a GA cDNA (pGA12) that was isolated from an oligo(dT)-primed rat kidney lambda gt10 library. This segment contains numerous AU-rich regions, four potential stem-loop structures, and a 48 base pair repeat of CA dinucleotides. Such domains may contribute to the increased stability of the GA mRNA that occurs in response to metabolic acidosis. PMID- 1918003 TI - A serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases. AB - We identified a 60-kDa diisopropylfluorophosphate-(DFP) reactive protein in human bronchoalveolar lavage fluid, at a yield of 50-100 pmol/lavage. The protein is associated with the cell-free lavage fluid sediment, which consists mainly of surfactant. [3H]DFP labeling is inhibited by heating to 56 degrees C, 2 mM phenylmethylsulfonylfluoride and 1 mM bis(4-nitrophenyl)-phosphate. An identical 60-kDa [3H]DFP-reactive protein is present in the insoluble fraction of alveolar macrophage-conditioned culture medium and in total membrane preparations of alveolar macrophages. The [3H]DFP-labeled protein was purified approximately 30 fold from lavage fluid sediment by size-exclusion (Sephacryl S-200) and ion exchange (Mono-Q) chromatography. Cyanogen bromide treatment of the partially purified protein produced a major labeled peptide of 14 kDa with an NH2-terminal sequence 90% identical to a region of form 1 rabbit liver microsomal carboxylesterase. Esterase activity in unlabeled starting material, detected using p-nitrophenyl valerate as substrate, copurified with the [3H]DFP-labeled enzyme. Degenerate oligonucleotide primers were designed based on the partial amino acid sequence and on a highly conserved region of known liver carboxylesterase sequences. Polymerase chain reaction using these primers and reverse-transcribed human alveolar macrophage mRNA yielded a 354-base pair product which was then used to screen a human alveolar macrophage cDNA library. A complete esterase sequence was obtained from two incomplete, overlapping clones, and is virtually identical to human liver carboxylesterase partial sequences. Northern blot analysis demonstrated a single approximately 1.7-kilobase transcript in human monocytes and alveolar macrophages, with much higher levels in the latter. These data indicate that human alveolar macrophages both contain and release a serine esterase that is apparently identical to liver microsomal carboxylesterase. Its enzymatic profile suggests it is a major component of alveolar macrophage-nonspecific esterase activity. We hypothesize that it acts as a detoxication enzyme in the lung. PMID- 1918002 TI - Adhesion of Bordetella pertussis to sulfatides and to the GalNAc beta 4Gal sequence found in glycosphingolipids. AB - The adherence of the human respiratory pathogen, Bordetella pertussis, to purified glycosphingolipids was investigated using thin layer chromatography overlay assays. Both virulent and avirulent strains of B. pertussis bound to asialo GM1. The bacterium did not bind to the gangliosides GM1, GD1a, GD1b, and GT1b, nor to lactosylceramide, trihexosylceramide, globoside, or Forssman antigen. However, after treatment of the chromatography plates with sialidase, B. pertussis bound to the gangliosides GM1, GM2, GD1a, GD1b, and GT1b but not to GM3. Comparison of the oligosaccharide structures of these gangliosides suggests that the minimum sugar structure needed for avid bacterial binding is GalNAc beta 4Gal. This structure has been previously implicated as a receptor for other human respiratory pathogens (Krivan, H. C., Roberts, D. D., Ginsburg, V. (1988) Proc. Natl. Acad. Sci. U.S.A 85, 6157-6161). Virulent strains of B. pertussis also bound specifically to sulfatide. This response was dose-dependent and inhibited by the anionic polysaccharide dextran sulfate. The sulfated-sugars dextran sulfate, fucoidan, and heparin inhibited the attachment of virulent strains of B. pertussis to human WiDr cells and to hamster trachea cells indicating that sulfatides on the surface of mammalian cells may function as a receptor for B. pertussis. The occurrence of both sulfatides and asialo GM1 in human lung and trachea suggests that these glycolipids may serve as specific receptors for B. pertussis. PMID- 1918004 TI - Multiple interacting sites regulate astrocyte-specific transcription of the human gene for glial fibrillary acidic protein. AB - The gfa gene encodes glial fibrillary acidic protein, an intermediate filament protein found almost exclusively in astrocytes. Transient transfection studies with a chloramphenicol acetyltransferase reporter gene were used to identify regions of the gfa gene responsible for its expression. Three regions, A, B, and D, were found to be important. The D region is located near the basal promoter, while A and B are next to each other about 1500 bp further upstream. The regions contain several sequences homologous to binding sites of known transcription factors, and in addition, each contains an identical novel 10-bp motif. The A, B, and D regions act in a cell-specific manner; when joined to the SV 40 early promoter, they enhance transcription in the glial cell line U251, but not in the nonglial cell line HepG2. Consistent with this observation, the DNase I footprint produced in these regions by nuclear extract from U251 cells differs from that produced by an extract from HepG2 cells. The B region appears to be the most active of the three, as by itself it stimulates strong cell-specific transcription, whereas addition of the other two regions has little effect. When the B region is at its normal distance from the basal promoter, deletion of D severely reduces transcription, but when B is placed near the promoter, D is unimportant. This suggests that the D region may function primarily to promote interactions that bring B close to the promoter. PMID- 1918005 TI - Structural homology among mammalian and Saccharomyces cerevisiae isoprenyl protein transferases. AB - Farnesyl-protein transferase (FTase) purified from rat or bovine brain is an alpha/beta heterodimer, comprised of subunits having relative molecular masses of approximately 47 (alpha) and 45 kDa (beta). In the yeast Saccharomyces cerevisiae, two unlinked genes, RAM1/DPR1 (RAM1) and RAM2, are required for FTase activity. To explore the relationship between the mammalian and yeast enzymes, we initiated cloning and immunological analyses. cDNA clones encoding the 329-amino acid COOH-terminal domain of bovine FTase alpha-subunit were isolated. Comparison of the amino acid sequences deduced from the alpha-subunit cDNA and the RAM2 gene revealed 30% identity and 58% similarity, suggesting that the RAM2 gene product encodes a subunit for the yeast FTase analogous to the bovine FTase alpha subunit. Antisera raised against the RAM1 gene product reacted specifically with the beta-subunit of bovine FTase, suggesting that the RAM1 gene product is analogous to the bovine FTase beta-subunit. Whereas a ram1 mutation specifically inhibits FTase, mutations in the CDC43 and BET2 genes, both of which are homologous to RAM1, specifically inhibit geranylgeranyl-protein transferase (GGTase) type I and GGTase-II, respectively. In contrast, a ram2 mutation impairs both FTase and GGTase-I, but has little effect on GGTase-II. Antisera that specifically recognized the bovine FTase alpha-subunit precipitated both bovine FTase and GGTase-I activity, but not GGTase-II activity. Together, these results indicate that for both yeast and mammalian cells, FTase, GGTase-I, and GGTase-II are comprised of different but homologous beta-subunits and that the alpha subunits of FTase and GGTase-I share common features not shared by GGTase-II. PMID- 1918006 TI - Mechanism of DNA A protein-dependent pBR322 DNA replication. DNA A protein mediated trans-strand loading of the DNA B protein at the origin of pBR322 DNA. AB - pBR322 DNA can be replicated via a DNA A-dependent pathway mediated by its binding to the two DNA A-binding sites (dnaA boxes) present near the plasmid origin. DNA synthesis requires the transcription of RNA II (the leading-strand primer precursor) to generate a specific unwound structure in the region containing the dnaA boxes. In this structure, the DNA containing the dnaA boxes can take the form of either a RNA II-parental H strand pBR322 DNA hybrid opposed by the displaced parental L strand (in the absence of RNase H and DNA polymerase I), or a nascent leading strand-parental H strand DNA duplex opposed by the displaced parental L strand (in the presence of RNase H and DNA polymerase I). These findings defined three types of potential sites for productive DNA A binding: (i) the displaced parental L single strand, (ii) a hairpin formed by the inverted repeat of the two dnaA boxes, and (iii) either the RNA-DNA duplex or the nascent leading strand-parental DNA duplex. By using a combination of: (i) inhibition of the replication of a plasmid carrying oriC by oligonucleotides of various dnaA box sequences and conformation, (ii) a gel mobility shift assay to measure DNA A binding to the same oligonucleotide substrates, (iii) replication of pBR322 DNA templates with either one or no dnaA box, and (iv) photocross linking to demonstrate DNA A binding to an RNA-DNA hybrid, evidence is presented here that DNA A-mediated pBR322 DNA replication proceeds by a mechanism in which DNA A binds to the duplex side of the unwound origin structures and loads the DNA B protein in trans to the displaced parental L strand DNA. PMID- 1918007 TI - ATP-dependent transport of taurocholate across the hepatocyte canalicular membrane mediated by a 110-kDa glycoprotein binding ATP and bile salt. AB - Direct photoaffinity labeling of liver plasma membrane subfractions enriched in sinusoidal and canalicular membranes using [35S]adenosine 5'-O-(thiotriphosphate) ([35S]ATP gamma S) allows the identification of ATP-binding proteins in these domains. Comparative photoaffinity labeling with [35S]ATP gamma S and with the photolabile bile salt derivative (7,7-azo-3 alpha, 12 alpha-dihydroxy-5 beta-[3 beta-3H]-cholan-24-oyl-2'- aminoethanesulfonate followed by immunoprecipitation with a monoclonal antibody (Be 9.2) revealed the identity of the ATP-binding and the bile salt-binding canalicular membrane glycoprotein with the apparent Mr of 110,000 (gp110). The isoelectric point of this glycoprotein was 3.7. Transport of bile salt was studied in vesicles enriched in canalicular and sinusoidal liver membranes. Incubation of canalicular membrane vesicles with [3H] taurocholate in the presence of ATP resulted in an uptake of the bile salt into the vesicles which was sensitive to vanadate. ATP-dependent taurocholate transport was also observed in membrane vesicles from mutant rats deficient in the ATP-dependent transport of cysteinyl leukotrienes and related amphiphilic anions. Substrates of the P-glycoprotein (gp170), such as verapamil and doxorubicin, did not interfere with the ATP-dependent transport of taurocholate. Reconstitution of purified gp110 into liposomes resulted in an ATP-dependent uptake of [3H]taurocholate. These results demonstrate that gp110 functions as carrier in the ATP-dependent transport of bile salts from the hepatocyte into bile. This export carrier is distinct from hitherto characterized ATP-dependent transport systems. PMID- 1918009 TI - Association of p21ras with cellular polypeptides. AB - p21ras specific antiserum was used to immunoprecipitate p21ras polypeptides from human A431 cells. In addition to p21ras, this antiserum precipitated a series of polypeptides with relative molecular weights of 150,000, 120,000, 105,000, and 50,000. The precipitation of these polypeptides was prevented by preincubation of the antiserum with an excess of purified Ras protein. These polypeptides do not share an epitope with p21ras, and two of them (120 and 150 kDa) copurify with a fraction of p21ras. The co-precipitation of p21ras with these polypeptides was detected in a variety of cell types. The pattern of the immunoprecipitates was consistently different in normal and ras-transformed cells. The 120- and 150-kDa polypeptides are phosphorylated on serine and threonine in A431 cells. Serum treatment resulted in a 2-fold increase in the phosphoserine content of the 120 kDa polypeptides. PMID- 1918008 TI - Characterization of a novel liver-specific enhancer in the human prothrombin gene. AB - The 5'-flanking sequence of the human prothrombin gene was isolated by screening a human liver phage library with a human prothrombin cDNA as a hybridization probe. A phage was identified that contained 3 kilobase pairs of DNA upstream of the initiator methionine codon. Primer extension studies showed that the major transcription initiation sites were located 23 and 36 base pairs upstream of the initiator codon. DNA sequences in the 5'-flanking region of the human prothrombin gene were then analyzed for cis-activating transcriptional activity by a transient expression system using the human growth hormone gene as the reporter gene. The chimeric expression vector was introduced into HepG2 cells, and secreted human growth hormone was monitored by using a radio-immunoassay. These studies showed that the 3-kilo-base pair fragment contained sequences that were sufficient for the initiation of transcription in HepG2 cells. Subsequent deletion studies showed that the 3-kilobase pair fragment contained two elements: a weak promoter in the region immediately upstream of the mRNA coding sequence and an enhancer located between nucleotides -860 and -940. The enhancer element was active at a distance and in either orientation. In addition, the enhancer was liver cell-specific and acted on heterologous promoters including the herpes simplex virus thymidine kinase promoter and the mouse metallothionein I promoter. Comparison of the nucleotide sequence of the enhancer with a DNA sequence data base showed the enhancer sequence to be unique. The enhancer sequence is flanked by an inverted repeat 5' CCTCCC 3' and contains a putative binding site for hepatic nuclear factor 1. Deoxyribonuclease I footprint analysis and linker scanning mutagenesis showed that the enhancer contains multiple protein binding motifs. Mutagenesis of the 3' boundary CCTCCC sequence eliminated the enhancer activity. Comparison with other liver genes showed the presence of the CCTCCC sequence in the hepatitis B virus enhancer, the alpha 1-antitrypsin promoter, and the fibrinogen beta-chain promoter, suggesting a functional role for this motif. PMID- 1918010 TI - Transcriptional regulation of the human lipoprotein lipase gene in 3T3-L1 adipocytes. AB - Lipoprotein lipase (LPL), a key enzyme in normal lipoprotein metabolism, has a complex pattern of regulation and tissue-specific expression. Several potential binding sites for transcription factors, including the recognition sequences for CCAAT/enhancer-binding protein and octamer-binding proteins (Oct) have been described in the 5'-flanking region of the human LPL gene. To identify elements which regulate the expression of LPL in adipocytes, plasmids containing deletion mutants of the 5'-LPL promoter region and the luciferase reporter gene were transfected in 3T3-L1 adipocytes. Deletions at -724, -565, -461, -368, -232, 167, -92, -35, and -17 relative to the transcriptional start site modified transcription from 100 to 162, 194, 185, 128, 63, 53, 29, and 0%, respectively, indicating the presence of negative (-724 to -565) and positive (-368 to -35) cis acting regulatory elements. Transfection of HepG2 cells, which do not synthesize LPL, with the same constructs resulted in a similar pattern of expression for the majority of the deletions. However, deletions between -724 and -368 base pairs resulted in a 75-100% increase in transcription in 3T3 adipocytes but not in HepG2 cells, indicating the presence of tissue-specific regulatory element(s) in this region. An important regulatory element affecting LPL transcription in adipocytes was identified by gel mobility shift assays and DNase I footprint analysis. Using these techniques, a nuclear protein(s) in 3T3-L1 adipocytes was shown to bind specifically to a fragment which included the proximal octamer recognition site (from -46 to -39) present in the LPL promoter. The DNA-protein complex comigrates with an electrophoretic band containing the Oct-1-DNA complex in BJA-B nuclear extracts and the DNA-protein complex was selectively competed only by DNA fragments containing the octamer sequence. Preincubation of 3T3-L1 nuclear extracts with an antibody directed against the POU domain of Oct-1 inhibited the formation of the DNA-protein complex. Deletion of the proximal octanucleotide motif from the plasmid containing the -461 fragment of the LPL promoter, resulted in a 79 and 76% decrease in the level of expression in transfected 3T3-L1 adipocytes and HepG2 hepatocytes, respectively. These combined results have established that the expression of LPL in adipocytes is modulated by multiple positive and negative regulatory elements within the 5'-flanking region of the LPL gene. A proximal octamer binding sequence which specifically interacts with a nuclear protein(s) that exhibits the characteristics of Oct-1 has been identified.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1918011 TI - Reconstitution of Ca(2+)-dependent K+ transport in erythrocyte membrane vesicles requires a cytoplasmic protein. AB - We have demonstrated that calcium-dependent potassium transport in erythrocytes requires the participation of a cytoplasmic protein. Activation of calcium dependent potassium transport causes an increase in the membrane-bound levels of this protein which is dependent on the calcium concentration and which is highly correlated (r = 0.791, p less than 0.0001) with the loss of potassium. Reconstitution of this transport pathway in sonicated erythrocyte membrane vesicles was achieved only in vesicles containing the cytoplasmic protein indicating a causal relationship in this transport system. The protein is found in high levels within the cytoplasm of erythrocytes (5.6 mg/ml red blood cells) and yet less than 1% of the protein located in the cytoplasm is required to bind to the membrane in order to initiate the potassium efflux. The analysis of rat organ homogenates demonstrated that this protein is located in most tissues with particular enrichment in adrenal glands, brain, lung, and blood. These results demonstrate that there is a cytoplasmic protein, herein named calpromotin, which is a necessary and sufficient cytoplasmic component of calcium-dependent potassium transport in erythrocytes and perhaps other tissues. PMID- 1918012 TI - Direct transcriptional regulation of the progesterone receptor by retinoic acid diminishes progestin responsiveness in the breast cancer cell line T-47D. AB - Retinoic acid (RA) treatment of T-47D human breast cancer cells results in a rapid decrease in the concentration of progesterone receptor (PR) mRNA which causes a slow loss of cellular PR protein (Clarke, C. L., Roman, S. D., Graham, J., Koga, M., Sutherland, R. L. (1990) J. Biol. Chem. 265, 12694-12700). The mechanisms involved are unknown and this study was undertaken to determine whether the decline in PR mRNA was due to transcriptional inhibition and to evaluate the functional consequences of the RA-mediated decrease in PR. The transcription rate of the PR gene was decreased by RA, and the effect was maximal 2-3 h after treatment. Cycloheximide cotreatment was unable to relieve the inhibitory effect of RA and PR transcription suggesting that the effect was not dependent on ongoing protein synthesis. There was no effect of RA on PR mRNA half life at the times examined (0-6 h of RA treatment). To determine the functional consequence of PR down-regulation the progestin-responsive plasmid pMSG-CAT was expressed transiently in T-47D cells which were then exposed to RA for 24 h. RA pretreated cells were then treated with the synthetic progestin ORG 2058 and the extent of progestin stimulation of chloramphenicol acetyltransferase (CAT) activity measured. ORG 2058 treatment resulted in an induction of CAT activity which was maximal at a progestin concentration of 1 nM. Interestingly, the ability of ORG 2058 to induce CAT activity was decreased in RA-pretreated cells. The diminished progestin responsiveness of RA-pretreated cells was confirmed in separate experiments which showed that the progestin inducibility of TGF-alpha mRNA was also decreased in cells treated with ORG 2058 following pretreatment with RA for 24 h. These data demonstrate that RA decreases PR mRNA concentrations by direct transcriptional inhibition, leading to decreased cellular PR concentrations. The decreased levels of PR result in impaired responsiveness to progestins and this suggests that RA derived from dietary vitamin A may have a role in modulating cellular sensitivity to progestins. PMID- 1918013 TI - Scanning mutagenesis of interleukin-8 identifies a cluster of residues required for receptor binding. AB - In order to identify residues required for the binding of interleukin-8 (IL-8) to its receptor, mutants were constructed in which clusters of charged amino acids were systematically replaced with alanine along the entire IL-8 sequence. The mutants were tested for their ability to induce a receptor-mediated rise in cytosolic free Ca2+, a property of wild-type IL-8 which can readily be detected by flow cytometry using neutrophils loaded with the calcium probe Indo-1. Eleven of the 12 mutants caused neutrophil calcium mobilization at 5 nM; the exception being a triple alanine mutant at positions K3, E4, and R6, which was inactive at all concentrations tested (150 nM maximum). A second set of mutants was generated in which residues 1-15 were individually mutated to alanine. Mutants E4A, L5A, or R6A were all inactive in the Ca2+ assay at 5 nM and competed poorly with 125I-IL 8 for neutrophil receptor binding; I10A, E4A, L5A, and R6A had approximately 30-, 100-, 100-, and 1000-fold reduced affinity, as compared with control IL-8, respectively. The nuclear magnetic resonance structure of IL-8 indicates that, in solution, the side chains of E4, L5, R6, and I10 point away from the core of the protein and do not participate in any intramolecular hydrogen bonds or salt bridges (Clore, G. M., and Gronenborn, A. M. (1991) J. Mol. Biol. 217, 611-620). PMID- 1918014 TI - Membrane markers of endoplasmic reticulum preserved in autophagic vacuolar membranes isolated from leupeptin-administered rat liver. AB - We isolated membranes from leupeptin-induced autophagic vacuoles and compared them with lysosomal membranes purified from dextran-administered rats. In protein composition, autophagic vacuole membranes prepared from long term-starved (36 h) rats bear marked resemblance to lysosomal membranes, whereas vacuole membranes prepared from short term-starved (12 h) animals differ significantly from lysosomal membranes. Immunoblotting analyses showed that only autophagic vacuole membranes from short term-starved rats possess endoplasmic reticulum markers such as cytochrome P450 and NADPH-cytochrome c reductase. None of the membranes contain sialyltransferase, a Golgi membrane marker. In experiments in which rats were starved after feeding to induce autophagy, the appearance of the endoplasmic reticulum markers occurred during 6-12 h of starvation, concomitantly with increases in vacuolar proteins and sequestered cytosolic aldolase. The endoplasmic reticulum membrane markers and sequestered aldolase declined gradually after 20-36 h of starvation, suggesting that prolonged starvation causes no further increase in the formation of autophagic vacuoles but an increase in the population of matured autophagic vacuoles. Thus, the prominent markers of endoplasmic reticulum from which autophagosomes originate are well preserved in autophagic vacuole membranes, and retention of these markers is highly dependent on the formation and subsequent maturation process of autophagic vacuoles. PMID- 1918015 TI - Purification and characterization of yeast RNA polymerase II transcription factor b. AB - Heat treatment of yeast nuclear extracts abolished the capacity to initiate transcription at RNA polymerase II promoters. Activity was restored by the addition of both recombinant yeast TFIID and partially purified factor b, a yeast fraction shown previously to be required for polymerase II transcription. On the basis of this assay with heat-treated extract, factor b was purified to virtual homogeneity. The factor appears to comprise polypeptides of approximately 85, 75, and 50 kDa, since these three polypeptides co-purify with activity, and since a native mass of about 200 kDa is estimated from glycerol gradient sedimentation and gel filtration. PMID- 1918016 TI - Mutational analysis of the cytoplasmic tail of the human transferrin receptor. Identification of a sub-domain that is required for rapid endocytosis. AB - It has been reported that the sequence Tyr20-X-Arg-Phe23 present within the cytoplasmic tail of the transferrin receptor may represent a tyrosine internalization signal (Collawn, J.F., Stangel, M., Kuhn, L.A., Esekogwu, V., Jing, S., Trowbridge, I.S., and Tainer, J. A. (1990) Cell 63, 1061-1072). However, as Tyr20 is not conserved between species (Alvarez, E., Girones, N., and Davis, R. J. (1990) Biochem. J. 267, 31-35), the functional role of the putative tyrosine internalization signal is not clear. To address this question, we constructed a series of 32 deletions and point mutations within the cytoplasmic tail of the human transferrin receptor. The effect of these mutations on the apparent first order rate constant for receptor endocytosis was examined. It was found that the region of the cytoplasmic tail that is proximal to the transmembrane domain (residues 28-58) is dispensable for rapid endocytosis. In contrast, the distal region of the cytoplasmic tail (residues 1-27) was found to be both necessary and sufficient for the rapid internalization of the transferrin receptor. The region identified includes Tyr20-X-Arg-Phe23, but is significantly larger than this tetrapeptide. It is therefore likely that structural information in addition to the proposed tyrosine internalization signal is required for endocytosis. To test this hypothesis, we investigated whether a heterologous tyrosine internalization signal (from the low density lipoprotein receptor) could function to cause the rapid endocytosis of the transferrin receptor. It was observed that this heterologous tyrosine internalization signal did not allow rapid endocytosis. We conclude that the putative tyrosine internalization signal (Tyr20-Thr-Arg-Phe23) is not sufficient to determine rapid endocytosis of the transferrin receptor. The data reported here indicate that the transferrin receptor internalization signal is formed by a larger cytoplasmic tail structure located at the amino terminus of the receptor. PMID- 1918017 TI - Purification and molecular cloning of succinyltransferase of the rat alpha ketoglutarate dehydrogenase complex. Absence of a sequence motif of the putative E3 and/or E1 binding site. AB - Full-length cDNA clones for succinyltransferase of the rat alpha-ketoglutarate dehydrogenase complex were isolated from rat heart cDNA libraries in lambda gt11. The cDNA clones were identified as those for rat succinyltransferase by the identity of their predicted amino acid sequence with the NH2-terminal amino acid sequence of rat succinyltransferase determined by protein chemical analysis and the known amino acid sequence of bovine succinyltransferase. The clone with the longest cDNA consisted of 2747 base pairs and coded for a leader peptide of 56 amino acid residues and a mature protein of 386 amino acid residues. The primary structure of rat succinyltransferase showed close similarity to Escherichia coli and Azotobacter vinelandii succinyltransferases, in the COOH-terminal part forming the lipoyl-binding domain and the NH2-terminal part forming the inner core-catalytic domain. However, the rat succinyltransferase did not contain a sequence motif that has been found as an E3- and/or E1-binding site in the dihydrolipoamide acyltransferases of three alpha-ketoacid dehydrogenase complexes (Hummel, K. B., Litwer, S., Bradford, A. P., Aitken, A., Danner, D. J., and Yeaman, S. J. (1988) J. Biol. Chem. 263, 6165-6168, Reed, L. J., and Hackert, M. L. (1990) J. Biol. Chem. 265, 8971-8974). The absence of this sequence was confirmed by direct sequencing of the polymerase chain reaction product of rat heart mRNA and by computer analysis. These results show that the rat succinyltransferase does not have the sequence motif of the putative E3- and/or E1-binding site. PMID- 1918018 TI - Association of type II cAMP-dependent protein kinase with p34cdc2 protein kinase in human fibroblasts. AB - Previous independent studies suggested that type II cAMP-dependent protein kinase and the p34cdc2 protein kinase cell cycle regulator co-localize at centrosomes. In order to investigate whether there is an association of type II cAMP-dependent protein kinase with p34cdc2 in human fibroblasts, we used three different approaches. First, the regulatory subunits RI and RII were photoaffinity-labeled with 8-N3-[32P]cAMP, and anti-p34cdc2 immunoprecipitates were screened for the presence of either RI or RII regulatory subunits by one- or two-dimensional gel electrophoresis. Second, anti-RII alpha immunoprecipitates were screened for the presence of p34cdc2 by Western blot using three different affinity-purified antibodies recognizing different domains of human p34cdc2. Conversely, anti p34cdc2 immunoprecipitates (three different antibodies), as well as the material retained on p13suc1-Sepharose Bio-Beads, which binds specifically p34cdc2, were screened for the presence of RII alpha. Finally, we have looked for cAMP dependent protein kinase activity specifically inhibited by PKI in immunoprecipitates obtained from extracts treated with different anti-p34cdc2 antibodies. All these experiments gave concordant results and demonstrate that at least at G0/G1, human fibroblasts contain a complex of active type II cAMP dependent protein kinase associated through its RII alpha subunit with p34cdc2. PMID- 1918020 TI - Action of RecBCD enzyme on Holliday structures made by RecA. AB - In vitro, Escherichia coli RecA protein acts upon gapped and partially homologous linear duplex DNA to generate recombination products linked by Holliday junctions. When strand exchange reactions are supplemented with purified RecBCD enzyme, we observe the formation of products that resemble "patch" recombinants. The formation of "splice" recombinant products was not observed. The individual subunits, RecB, RecC, or RecD, had no effect on RecA protein-mediated strand exchange nor on the Holliday junctions formed in the reaction. Analysis of the way in which patch products arise indicates exonucleolytic digestion of the linear arms of the recombination intermediates (alpha-structures) by RecBCD enzyme. We find no evidence for specific resolution events at the site of the Holliday junction by RecBCD enzyme using these DNA substrates. PMID- 1918021 TI - Regulation of endothelin-1 gene expression by Fos and Jun. AB - The endothelin peptides constitute a family of potent vasoconstrictor molecules. Endothelin-1 (ET1) is secreted by vascular endothelial cells and may have a role in the regulation of vascular tone. To better understand the function of ET1, we have investigated the transcriptional regulation of the ET1 gene. Utilizing reporter gene transfection experiments, we have previously identified two promoter regions, located at base pairs -148 to -117 (Region A) and -117 to -98 (Region B) of the ET1 gene. Both regions are necessary for high level ET1 transcription in endothelial cells. A nuclear protein binding to the GATA motif in Region A has been identified and proven to be necessary for expression of the ET1 gene. However, the cis-acting sequences and their cognate binding proteins for Region B have not been investigated. To identify protein binding motifs in Region B we performed DNase I footprinting and gel mobility shift assays using a DNA fragment encoding base pairs -204 to -94 of the ET1 gene. Results from these studies indicated that the AP1 consensus sequence (GTGACTAA) in Region B as the only protein-binding motif. Site-directed mutagenesis of the ET1 AP1 site resulted in a 30-fold reduction in promoter activity, establishing the functional significance of this sequence. Additional experiments investigated the role of Jun and Fos in ET1 transcription. By employing antisera to Jun and Fos in gel mobility shift assays, both of these proteins were identified as endothelial cell nuclear proteins binding to the ET1 AP1 sequence. In trans-activation experiments, we showed that cotransfection of c-fos and c-jun expression plasmids markedly increased the transcription rate of chloramphenicol acetyltransferase reporter plasmids containing three synthetic ET1 AP1 sites. Taken together, these data indicate the importance of the AP1 recognition sequence, and the role of Fos and Jun proteins in the regulation of ET1 gene transcription. PMID- 1918019 TI - Probing the role of cysteine residues in the CheR methyltransferase. AB - The CheR methyltransferase catalyzes the transfer of methyl groups from S adenosylmethionine to specific glutamyl residues in bacterial chemoreceptor proteins. Studies with sulfhydryl reagents such as p-chloromercuribenzoate, N ethylmaleimide, and 5,5'-dithiobis(2-nitrobenzoate) suggest that a cysteine residue is required for enzyme activity. The nucleotide sequence of the cheR gene predicts a 288-amino acid protein with cysteine residues at positions 31 and 229. To ascertain the role of these cysteine residues in the structure and function of the enzyme, oligonucleotide-directed mutagenesis was used to change each cysteine to serine. Whereas the Cys229-Ser mutation had essentially no effect on transferase activity, the Cys31-Ser mutation caused an 80% decrease in enzyme activity. The double mutant in which both cysteines were replaced by serines also had markedly reduced transferase activity. Preincubation of the wild type or Cys229-Ser proteins with either S-adenosylmethionine or beta-mercaptoethanol protected it from inhibition by sulfhydryl reagents, whereas prior incubation with the second substrate, the Tar receptor, gave partial protection. From these studies, Cys31 appears to be necessary for enzyme activity, and it seems to be located in the vicinity of the active site. PMID- 1918022 TI - Binding and calcium-induced aggregation of laminin onto lipid bilayers. AB - Direct binding of laminin in the form of its complex with nidogen to planar lipid bilayers was demonstrated with total internal reflection fluorescence microscopy. Binding occurred equally well to zwitterionic (phosphatidylcholine) and negatively charged (phosphatidylglycerol) lipids and was enhanced by sulfatides but only at nonphysiological molar ratios higher than 30 mol %. Strong interactions with lipid bilayers were also observed for bovine serum albumin. This explains a strong inhibition of laminin binding by this protein. However, binding of laminin to sulfatide-rich bilayers was not completely inhibited. Observable by the microscopic technique was the formation of laminin clusters on the surface of the bilayer which occurred concomitantly with binding. Both processes were strongly enhanced by the presence of calcium. These results show that calcium-induced laminin self-assembly is enhanced at lipid surfaces. PMID- 1918023 TI - Yeast RNA polymerase II subunit RPB9 is essential for growth at temperature extremes. AB - The Saccharomyces cerevisiae RNA polymerase II subunit gene RPB9 was isolated and sequenced. RPB9 is a single copy gene on chromosome VII. The RPB9 sequence predicts a protein of 122 amino acids with a molecular mass of 14,200 Da. The yeast RPB9 subunit is similar in size and sequence to a protein encoded by DNA adjacent to the suppressor of the Hairy Wing gene in Drosophila melanogaster. Deletion of the RPB9 gene produced cells that were heat- and cold-sensitive. The RPB9 subunit, like the previously described RNA polymerase II subunit RPB4, is not essential for synthesis of mRNA, but is required for normal cell growth over a wide temperature range. PMID- 1918024 TI - Autoflavinylation of apo6-hydroxy-D-nicotine oxidase. AB - 6-Hydroxy-D-nicotine oxidase (6-HDNO) was expressed in Escherichia coli JM109 cells from the recombinant plasmid pAX-6-HDNO as a beta-galactosidase-6-HDNO fusion protein. Affinity chromatography of the fusion protein on p-aminobenzyl-1 thio-beta-galactopyranoside-agarose and subsequent digestion with protease Xa yielded highly purified apo6-HDNO. Incubation of the purified protein with [14C]FAD demonstrated that flavinylation of apo6-HDNO proceeds autocatalytically. Phosphorylated three-carbon compounds such as glycerol-3-P, which are known to stimulate the formation of the histidyl (N3)-(8 alpha) FAD between apo6-HDNO and FAD (Brandsch, R., and Bichler, V. (1989) Eur. J. Biochem. 182, 125-128), could be replaced in their action by high concentrations of glycerol (45%) or sucrose (20%). These substances apparently induced and stabilized a conformational state of the apoenzyme compatible with covalent attachment of FAD. In the absence of glycerol the apoenzyme readily lost the ability to form holoenzyme at temperatures above 30 degrees C. Holoenzyme formation protected the 6-HDNO polypeptide from this thermal denaturation. Autoflavinylation of 6-HDNO was inhibited by the sulfhydryl reagents dithionitrobenzoate or N-ethylmaleimide. Inhibition was prevented by mercaptoethanol or FAD, but not 6-hydroxy-D-nicotine, the substrate of the holoenzyme. A cysteine-thiol group may therefore be involved in reactions leading to the covalent attachment of FAD to apo6-HDNO. When flavinylation of apo6-HDNO proceeded under anaerobic conditions, the amount of incorporation of [14C]FAD into the polypeptide was indistinguishable from reactions performed in the presence of O2. None of the FAD-derivatives (8 demethyl-FAD, 8-chloro-FAD, and 5-deaza-FAD) could replace FAD in holoenzyme formation. The failure of covalent attachment of 5-deaza-FAD to apo6-HDNO is in agreement with the assumption that the quinone methide form of the isolloxazine ring is an intermediate in the flavinylation reaction. PMID- 1918025 TI - The specific binding, bending, and unwinding of DNA by RsrI endonuclease, an isoschizomer of EcoRI endonuclease. AB - To determine whether RsrI endonuclease recognizes and cleaves the sequence GAATTC in duplex DNA similarly to its isoschizomer EcoRI we initiated a functional comparison of the two enzymes. Equilibrium binding experiments showed that at 20 degrees C RsrI endonuclease binds to specific and nonspecific sequences in DNA with affinities similar to those of EcoRI. At 0 degrees C the affinity of RsrI for its specific recognition sequence is reduced 7-fold whereas the affinity for noncanonical sequences remains relatively unchanged. Unlike EcoRI, incubation of RsrI endonuclease with N-ethylmaleimide inactivates the enzyme; however, preincubation with DNA prevents the inactivation. The N-ethylmaleimide-treated enzyme fails to bind DNA as assayed by gel mobility shift assays. Comparison of the deduced amino acid sequences of RsrI and EcoRI endonucleases suggests that modification of Cys245 is responsible for the inactivation. Fe(II). EDTA and methidiumpropyl-EDTA.Fe(II) footprinting results indicate that RsrI, like EcoRI, protects 12 base pairs from cleavage when bound to its specific recognition sequence in the absence of Mg2+. RsrI bends DNA by approximately 50 degrees, as determined by measuring the relative electrophoretic mobilities of specific RsrI DNA complexes with the binding site in the center or near the end of the DNA fragment. This value is similar to that reported for EcoRI. RsrI also unwinds the DNA helix by 25 degrees +/- 5 degrees, a value close to that reported for EcoRI endonuclease. Collectively, these results indicate that the overall structural changes induced in the DNA by the binding of RsrI and EcoRI endonucleases to DNA in the absence of Mg2+ are similar. In the accompanying paper (Aiken, C. R., McLaughlin, L. W., and Gumport, R. I. (1991) J. Biol. Chem. 266, 19070-19078) we present results of studies of RsrI endonuclease using oligonucleotide substrates containing base analogues which suggest differences in the ways the two enzymes cleave DNA. PMID- 1918026 TI - The highly homologous isoschizomers RsrI endonuclease and EcoRI endonuclease do not recognize their target sequence identically. AB - Using a series of decadeoxyribonucleotides containing base analogues as substrates we measured the steady-state kinetic parameters for the reaction catalyzed by RsrI endonuclease and compared the results to those with its isoschizomer EcoRI. The kinetics of RsrI cleavage are affected by each substitution, with the effects being generally more deleterious than with EcoRI, as shown by the greater reduction in the specificity constant kcat/KM. The magnitudes of the effects of several substitutions are consistent with the formation of direct enzyme-nucleobase contacts at the indicated positions. With substrates containing 2-amino-purine or 2,6-diaminopurine at the central adenine or uracil at the outermost thymine in the recognition sequence, cleavage by RsrI was very slow, less than one-tenth the rate of the corresponding EcoRI-catalyzed reaction. The lower tolerance of RsrI endonuclease for functional group changes in its recognition site may reflect differences in the mechanisms of DNA recognition by the two enzymes. Although RsrI and EcoRI endonucleases bind with similar affinities to specific and nonspecific DNA sequences and appear to introduce similar structural distortions in DNA upon binding, the use of substrate analogues reveals significant differences at the level of catalysis in the mechanisms by which these two endonucleases recognize the duplex sequence GAATTC. PMID- 1918027 TI - The laying hen expresses two different low density lipoprotein receptor-related proteins. AB - We have identified, by a combination of ligand, 45Ca2+, and immunoblotting, two large membrane proteins akin to the mammalian so-called low density lipoprotein (LDL) receptor-related protein (LRP) in chicken tissues. LRP has thus far been demonstrated only in mammalian species where it is thought to act as a receptor for proteinase-alpha 2-macroglobulin complexes and/or chylomicron remnants, lipoproteins not produced in birds. One of the chicken LRPs was demonstrated in liver, and has the same apparent Mr and hallmark biochemical properties as rat liver LRP. The other chicken LRP is smaller (approximately 380 kDa) and is expressed in ovarian follicles, but is undetectable in liver. Immunological analysis demonstrated a lack of cross-reactivity between the two LRPs, as well as between them and the previously identified chicken oocyte-specific 95-kDa receptor for the yolk precursors, very low density lipoprotein, and vitellogenin (Stifani, S., Barber, D. L., Nimpf, J., and Schneider, W. J. (1989) Proc. Natl. Acad. Sci. U.S.A. 87, 1955-1959). As shown by ligand blotting, both chicken LRPs have the ability to interact with vitellogenin, a property they share not only with rat LRP, but also with mammalian LDL receptors. To obtain independent confirmation of the ligand blotting results, the smaller (follicular) LRP was purified and high-affinity binding of vitellogenin to it was demonstrated by a solid-phase filtration binding assay. Amino acid sequences of tryptic fragments of the smaller LRP were obtained, and its homology with human LRP demonstrated through unambiguous alignment of three fragments. Both chicken LRPs, the chicken oocyte 95-kDa receptor, as well as rat LRP, could be shown by ligand blotting to interact specifically with chicken serum alpha 2-macroglobulin. In addition, human apolipoprotein E, a ligand implicated in receptor-mediated metabolism of chylomicron remnants, also binds to the smaller chicken LRP, further emphasizing the similarities between LDL receptors and related proteins from a variety of species. In analogy to the known dichotomy of chicken LDL receptors, which is characterized by the production of the 95-kDa oocyte-specific receptor on one hand and a 130-kDa LDL receptor that is exclusively expressed in somatic cells (Hayashi, K., Nimpf, J., and Schneider, W. J. (1989) J. Biol. Chem. 264, 3131 3139), it appears that the smaller and larger chicken LRPs also may be restricted to the oocyte and somatic cells, respectively. PMID- 1918028 TI - DNA polymerase III holoenzyme. Components, structure, and mechanism of a true replicative complex. PMID- 1918029 TI - Novel proliferative effect of phospholipase A2 in Swiss 3T3 cells via specific binding site. AB - Phospholipase A2 (PLA2), EC 3.1.1.4, which catalyzes the release of free fatty acids from the sn-2 position of glycerophospholipids, has been extensively studied from the viewpoint of eicosanoid production (Arita, H., Nakano, T., and Hanasaki, K. (1989) Prog. Lipid Res. 28, 273-301). Several lines of evidence suggest that extracellular PLA2 is pathophysiologically related to some disorders, including inflammation and hypersensitivity. Despite this, little is known of the precise mechanism of the pathological processes as well as their intrinsic correlation with dysfunction. Here, we report a novel PLA2 action on the proliferation of Swiss 3T3 fibroblasts via specific binding sites of approximately Mr 200,000. Pancreatic type PLA2 in the active form specifically recognized the sites and stimulated thymidine incorporation in DNA. Its inactive zymogen and other PLA2s from platelets, snake, and bee venoms showed much lesser activities. Although the physiological significance remains to be identified, our finding is the first to offer a new viewpoint on the effect of mammalian extracellular PLA2 on cellular function. PMID- 1918030 TI - Abnormal binding of factor VIII is linked with the substitution of glutamine for arginine 91 in von Willebrand factor in a variant form of von Willebrand disease. AB - von Willebrand factor (vWf) is a multimeric plasma glycoprotein that functions in hemostasis as the initiator of platelet adhesion to damaged blood vessels and as the carrier of Factor VIII (FVIII). Montgomery et al. (Montgomery, R.R., Hathaway, W.E., Johnson, J., Jacobsen, L., and Muntean, W. (1982) Blood 60, 201 207) reported a variant of von Willebrand disease characterized by the abnormal interaction between FVIII and a defective vWf. To identify the molecular basis of this abnormal interaction, we isolated platelet RNA from members of one of the affected families and determined the nucleotide sequence of the FVIII-binding domain encoded by the vWf mRNA. A single G to A transition at nucleotide 2561 was linked with disease expression and results in the substitution of Gln for Arg91 in mature vWf. A restriction fragment containing this mutation was introduced into a full-length vWf expression vector, and both wild type and mutant vWf were expressed in COS-7 cells. In a solid-phase binding assay, expressed vWf was captured with anti-vWf monoclonal antibody AVW1 and then incubated with 6.25-400 milliunits of recombinant FVIII. After washing, vWf-bound FVIII activity was determined with a chromogenic assay. Mutant vWf showed reduced binding of FVIII compared with wild type, suggesting that the substitution of Gln for Arg91 is the likely basis for the abnormal vWf/FVIII interaction in this von Willebrand disease variant. PMID- 1918031 TI - The inositol 1,4,5-trisphosphate-forming agonist histamine activates a ryanodine sensitive Ca2+ release mechanism in bovine adrenal chromaffin cells. AB - The role of a Ca(2+)-induced Ca2+ release (CICR) mechanism in the generation of agonist-induced increases of intracellular free Ca2+ concentration ([Ca2+]i) was studied in bovine adrenal chromaffin cells. In single cells, repetitive stimulations with caffeine at 200-s intervals evoked reproducible spikes of [Ca2+]i. Ryanodine, an agent that interacts with the CICR channel of muscle, inhibited the caffeine-induced spikes of [Ca2+]i in a "use-dependent" way. High affinity binding sites for [3H]ryanodine (Kd 3.3 nM, Bmax 26 fmol/mg protein) were also detected in membranes from chromaffin cells, supporting the presence of a caffeine- and ryanodine-sensitive CICR channel. Pretreatment of single cells with caffeine + ryanodine to reduce the size of the caffeine-sensitive Ca2+ compartment inhibited a subsequent spike of [Ca2+]i evoked by histamine, a D-myo inositol 1,4,5-trisphosphate-forming agonist. This demonstrates that a significant portion of the Ca2+ released by histamine comes from a caffeine- and ryanodine-sensitive pool. Ryanodine inhibited by 50% the size of [Ca2+]i spikes evoked by repetitive stimulation with histamine and did so in a use-dependent manner. These data suggest that, in addition to D-myoinositol 1,4,5 trisphosphate, activation of a caffeine- and ryanodine-sensitive CICR channel participates in the generation of histamine-induced release of intracellular Ca2+. PMID- 1918032 TI - Dramatic size variation of yeast mitochondrial RNAs suggests that RNase P RNAs can be quite small. AB - The gene coding for the AU-rich RNA required for mitochondrial RNase P activity in Saccharomyces cerevisiae codes for a 490-base RNA while that in Candida glabrata codes for a 227-base RNA. We have detected a 140-nucleotide RNA coded by the mitochondrial DNA from Saccharomycopsis fibuligera by hybridization with an oligonucleotide complementary to a conserved sequence found in mitochondrial and prokaryotic RNase P RNAs. DNA sequence analysis of the mitochondrial DNA from the region coding for this RNA revealed a second conserved sequence block characteristic of RNase P RNA genes and the presence of a downstream tRNA(Pro) gene. Like previously characterized mitochondrial RNase P RNAs, this small RNA is extremely AU-rich. The discovery of this 140-base RNA suggests that naturally occurring RNase P RNAs may be quite small. PMID- 1918033 TI - Mammalian seryl-tRNA synthetase associates with mRNA in vivo and has homology to elongation factor 1 alpha. AB - Previous work in our laboratories (Slobin, L. I., and Greenberg, J.R. (1988) Eur. J. Biochem. 173, 305-310) showed that messenger ribonucleoprotein (mRNP) particles possess a polypeptide component of approximately 62 kDa that appears to share a common epitope with eucaryotic elongation factor 1 alpha (EF-1 alpha). We report here that the previously unidentified mRNP constituent corresponds to seryl-tRNA synthetase (SerRS). Furthermore, we show that SerRS contains a sequence motif that is shared by both EF-1 alpha and glutaminyl-tRNA synthetase. We also find that the association of SerRS with mRNA depends on the functional state of the latter. Our data suggest that SerRS may participate directly in the initiation phase of protein synthesis. PMID- 1918034 TI - Isolation of a functional transferase component from the rat fatty acid synthase by limited trypsinization of the subunit monomer. Formation of a stable functional complex between transferase and acyl carrier protein domains. AB - Limited trypsinization of rat fatty acid synthase monomers results in cleavage at sites protected in the native dimer. A 47,000-Da polypeptide containing the transferase component was isolated from the digest and its location in the multifunctional polypeptide established. Both acetyl and malonyl moieties are transferred stoichiometrically from CoA ester to this polypeptide and each can replace the other, confirming that a single common site is utilized in the loading of these substrates onto the fatty acid synthase. Transferase activity of the 47,000-Da polypeptide decreases with increasing acyl donor chain length (malonyl = acetyl greater than butyryl greater than hexanoyl greater than octanoyl). Activity is inhibited by certain thiol-directed reagents, and protection is afforded by substrate suggesting the presence of a sensitive cysteine residue near the substrate binding site. The transferase was also able to utilize as acyl acceptor the Escherichia coli acyl carrier protein and the acyl carrier protein domain of the multifunctional fatty acid synthase. When the fatty acid synthase monomer was trypsinized under milder conditions, the 47,000 Da transferase domain could be isolated in association with the 8,000-Da acyl carrier protein domain. The transferase was capable of translocating substrate moieties from CoA ester donors to the associated acyl carrier protein. The results provide the first direct evidence that, in the head-to-tail oriented fatty acid synthase homodimer, functional communication between the transferase domain located near the end of one polypeptide and the acyl carrier protein domain located at the opposite end of the other polypeptide is facilitated by a stable physical interaction between these domains. PMID- 1918035 TI - The expression of a catalytically active cholesterol 7 alpha-hydroxylase cytochrome P450 in Escherichia coli. AB - We have recently cloned a full-length cDNA encoding the rat hepatic cholesterol 7 alpha-hydroxylase cytochrome P450 (P450c7) (Li, Y. C., Wang, D. P., and Chiang, J. Y. L. (1990) J. Biol. Chem. 265, 12012-12019), which catalyzes the rate limiting reaction of bile acid synthesis in the liver. By using the polymerase chain reaction, we have designed two P450c7 cDNAs. One has the second Met codon deleted and the third Thr codon replaced with an Ala. The other lacks codons for the NH2-terminal hydrophobic sequence of amino acids 2-24 (P450c7 delta 2-24). The cDNAs were separately cloned into the expression vector pKK233-2 and transformed into Escherichia coli. After induction with isopropyl-beta-D thiogalactopyranoside, bacteria harboring recombinant plasmids expressed a polypeptide which reacted with the antibody against cholesterol 7 alpha hydroxylase in immunoblots. The slightly modified full-length enzyme was expressed to 0.2% of the total bacterial lysate and was located in the membrane fraction, whereas P450c7 delta 2-24 was expressed at a 10-fold higher level (2%), of which 85% was in the cytosol and the remaining associated with the membranes. We have purified P450c7 delta 2-24 which showed a typical reduced-CO difference spectrum of cytochrome P450 and reconstituted cholesterol 7 alpha-hydroxylase activity in the presence of NADPH-cytochrome P450 reductase. P450c7 delta 2-24 has a similar Km for cholesterol (24.6 microM) but a lower Vmax (0.10 nmol/min) and a lower turnover number (1.93 min-1) as compared with the enzyme isolated from rat liver microsomes. The purified P450c7 delta 2-24 has an unique hydrophilic NH2 terminus and contains monomers and dimers in equal amounts. This is the first report demonstrating that a genetically engineered cytochrome P450 enzyme lacking a typical NH2-terminal hydrophobic sequence is mainly cytosolic and catalytically active. PMID- 1918036 TI - Multiple determinants for the high substrate specificity of an angiotensin II forming chymase from the human heart. AB - Human heart chymase, a chymotrypsin-like serine proteinase that hydrolyzes the Phe8-His9 bond in angiotensin I (Ang I) to yield the octapeptide hormone angiotensin II (Ang II) and His-Leu, is the most specific, efficient Ang II forming enzyme described. Other mammalian chymases display a much broader substrate specificity. To better define its substrate specificity, we have mapped the extended substrate-binding site of human heart chymase using Ang I analogs. The enzyme has a preference for aromatic amino acids phenylalanine, tyrosine, and tryptophan at the P1 site. At the S2 subsite there is a significant preference for proline over hydrophobic or hydrophilic amino acids. There is no clear preference for hydrophobic or hydrophilic amino acids at the S'1 and S'2 subsites, but an Ang I analog containing a P'1 proline is not hydrolyzed and one with a P'2 proline is hydrolyzed poorly. An increasing reduction in reactivity occurs when the P position amino acids in Ang I are deleted sequentially from the N terminus. An increase or decrease in the length of the His-Leu leaving group also produces a marked decrease in reactivity. No single determinant in Ang I is preeminently required for efficient catalysis, but several factors acting synergistically appear to be important. Thus, we propose that ideal substrates for human heart chymase should contain the structure nXaa-Pro-[Phe, Tyr, or Trp] Yaa-Yaa, where n greater than or equal to 6; Xaa = any amino acid; Yaa = any amino acid except proline. This structure exists in Ang I and neurotensin, both of which are good substrates for human heart chymase. These findings indicate that the selection of the scissile bond by the extended substrate-binding site of human heart chymase is more restricted than that in other chymases. PMID- 1918037 TI - Localization of the human tissue factor recognition determinant of human factor VIIa. AB - Tissue factor is an integral membrane glycoprotein that serves as an essential cofactor for the blood coagulation factor VIIa. Recent studies have attempted to localize the tissue factor recognition determinant of human factor VIIa. While several regions of factor VIIa have been implicated as important for tissue factor binding, the high affinity tissue factor recognition determinant of human factor VIIa is unknown. In order to define the determinant, we constructed a set of six chimeric proteins composed of portions of factor VII and factor IX. We then utilized the chimeras in competition experiments with 125I-labeled factor VIIa for recombinant tissue factor bound to an Immobilon-P membrane. The data indicate that the high affinity tissue factor recognition determinant of human factor VIIa is within the epidermal growth factor domains. PMID- 1918038 TI - Mixed ligand complexes of iron with cyanide and phenanthroline as new probes of metalloprotein electron transfer reactivity. Analysis of reactions involving rusticyanin from Thiobacillus ferrooxidans. AB - A family of 12 different mixed ligand complexes of iron with cyanide and substituted 1,10-phenanthroline was prepared. The electron transfer properties of each reagent were systematically manipulated by varying the substituent(s) on the aromatic ring system and the stoichiometry of the two types of ligands in the complex. Values for the standard reduction potentials of each member of this family of electron transfer reagents were determined and spanned from 500 to 900 mV. The one-electron transfer reactions between each of these substitution-inert reagents and the high potential blue copper protein, rusticyanin, from Thiobacillus ferrooxidans were studied by stopped flow spectrophotometry under acidic conditions. For comparison with the protein results, the kinetics of electron transfer between each of these reagents and sulfatoiron were also investigated. The Marcus theory of electron transfer was successfully applied to this set of kinetic data to demonstrate that 10 of the 12 reagents had equal kinetic access to the redox center of the rusticyanin and utilized the same reaction pathway for electron transfer. The utility of these synthetic electron transfer reagents in characterizing the electron transfer properties of very high potential, redox-active metalloproteins is illustrated. PMID- 1918040 TI - Inhibitor stabilization of human immunodeficiency virus type-2 proteinase dimer formation. AB - We report the first direct observation of the subunit self-association behavior of highly purified recombinant human immunodeficiency virus type-2 (HIV-2) proteinase. Multiple samples of enzyme were subjected to sedimentation equilibrium analytical ultracentrifugation sequentially at 8.8 degrees C and two pH values in the presence and absence of a C2 symmetric, peptidomimetic inhibitor. At both pH values the enzyme exhibited sedimentation equilibrium behavior which fit a monomer-dimer-tetramer model. In the absence of inhibitor, the apparent Kd for dimer formation was less than approximately 100 microM and the apparent Kd for the weaker dimer-tetramer association was greater than approximately 100 microM. In the presence of inhibitor, at either pH, dimer formation was more strongly favored as indicated by a approximately 5-14-fold decrease in the apparent Kd for dimer formation and a approximately 1.2-4-fold increase in the apparent Kd for tetramer formation. The enhanced formation of dimer and decrease in higher order self-associated forms in the presence of an inhibitor is consistent with inhibitor stabilization of an active dimer. The inhibitor-induced stabilization of the dimeric species is consistent with a model for substrate-induced formation of active proteinase dimers in virion assembly. PMID- 1918039 TI - Modification of histidine 56 in adrenodoxin with diethyl pyrocarbonate inhibited the interaction with cytochrome P-450scc and adrenodoxin reductase. AB - Three histidine residues of bovine adrenodoxin, His-10, His-56, and His-62, were modified with diethyl pyrocarbonate. The order of the modification among the three histidines were monitored by measuring the proton NMR spectra. The modified adrenodoxin exhibited reduced affinity for adrenodoxin reductase as determined in cytochrome c reductase activity. In the presence of cholesterol, the modified adrenodoxin induced a high spin form of cytochrome P-450scc on complex formation in the same manner as native adrenodoxin. The spectral titration showed that adrenodoxin modified with diethyl pyrocarbonate exhibited a 5-fold higher Kd value than that of native adrenodoxin. These effects of the modification of adrenodoxin on the affinities for the redox partners were not proportional to the number of modified histidines determined by the optical absorbance change at 240 nm. Modification of adrenodoxin up to 2 histidine residues did not affect the affinity for the redox partners, but further modification on the third one resulted in an increase of apparent Km in cytochrome c reductase activity by 2 fold and of Kd for cytochrome P-450scc by 5-fold. The 1H NMR spectra of the modified adrenodoxin unequivocally demonstrated that histidine residues at His-10 and His-62 reacted more readily with diethyl pyrocarbonate than His-56 did, indicating that modification of His-56 was responsible for the reduction of binding affinities of adrenodoxin for redox partners. These results are consistent with the proposal that the residue of His-56 in adrenodoxin has an essential role in the electron transfer mechanism where adrenodoxin functions as a mobile shuttle. PMID- 1918041 TI - Immunochemical mapping of antigenic regions on the human thyrotropin beta-subunit by antipeptide antibodies. AB - To study antigenic sites present in the beta-subunit of human thyrotropin (hTSH), we produced site-specific antibodies directed against synthetic peptides analogous to the 1-18, 44-59, and 85-112 regions of the thyrotropin beta-subunit. The hTSH beta(1-18) peptide-carrier conjugate elicited antisera capable of binding to both radiolabeled hTSH and its beta-subunit whereas antibodies elicited against the hTSH beta(44-59) peptide-carrier conjugate bound only to the peptide. Thus, the NH2-terminal region of hTSH beta appears to be accessible at the surface of the hormone whereas the hTSH beta(44-59) region may be poorly accessible. Two monoclonal antipeptide antibodies that bound to 125I-hTSH beta, designated as TS01 and TS02, were selected after immunization with the hTSH beta(85-112) peptide-carrier conjugate. The antigenic site recognized by TS01 was located on the eight COOH-terminal(105-112) amino acid residues. TS02 antibody bound to an antigenic region included within Cys95 and Cys105. Both antigenic sites appeared to be more accessible on the free hTSH beta than on the hormone. Immunoblots performed on various preparations containing TSH revealed that TS02 antibody detected the beta-subunit from both the human and bovine species but not the rat TSH beta. Under reducing conditions, a low molecular weight material was identified in hTSH beta, likely caused by intrachain nicking. PMID- 1918042 TI - The mevalonate pathway in the bloodstream form of Trypanosoma brucei. Identification of dolichols containing 11 and 12 isoprene residues. AB - The major surface antigen of the bloodstream form of Trypanosoma brucei, the variant surface glycoprotein, is attached to the plasma membrane via a glycosylphosphatidylinositol anchor. The biosynthesis of the glycosylphosphatidylinositol anchor, as well as the assembly of the asparagine linked oligosaccharide chains found on the variant surface glycoproteins, involves polyisoprenoid lipids that act as sugar carriers. Preliminary observations (Menon, A.K., Schwarz, R.T., Mayor, and Cross, G.A.M. (1990) J. Biol. Chem. 265, 9033-9042) suggested that the sugar carriers in T. brucei were short-chain polyisoprenoids containing substantially fewer isoprene residues than polyisoprenols in mammalian cells. In this paper we describe metabolic labeling experiments with [3H]mevalonate, as well as chromatographic and mass spectrometric analyses of products of the mevalonate pathway in T. brucei. We report that cells of the bloodstream form of T. brucei contain a limited spectrum of short chain dolichols and dolichol phosphates (11 and 12 isoprene residues). The total dolichol content was estimated to be 0.28 nmol/10(9) cells; the dolichyl phosphate content was 0.07 nmol/10(9) cells. The same spectrum of dolichol chain lengths was also found in a polar lipid that could be labeled with [3H]mevalonate, [3H]glucosamine, and [3H]mannose, and which was characterized as Man5GlcNAc2-PP-dolichol. The most abundant product of the mevalonate pathway identified in T. brucei was cholesterol (140 nmol/10(9) cells). Ubiquinone (0.09 nmol/10(9) cells) with a solanesol side chain was also identified. PMID- 1918043 TI - The active sites of cytochromes P450 IA1, IIB1, IIB2, and IIE1. Topological analysis by in situ rearrangement of phenyl-iron complexes. AB - The reactions of cytochromes P450 IA1, IIB1, IIB2, and IIE1 with phenyldiazene yield complexes with absorption maxima at either 474 or 480 nm. Anaerobic extraction of the prosthetic group from the phenyldiazene-treated proteins followed by its exposure to oxygen and strong acid produces an equal mixture of the four possible N-phenylprotoporphyrin IX regioisomers. Exposure of the anaerobically extracted heme complexes to oxygen in the absence of strong acid results in their decomposition to heme and products other than N phenylprotoporphyrin IX. These results show that the 474/480 nm absorption maxima are due to sigma phenyl-iron complexes. Treatment of the intact hepatic cytochrome P450 complexes with K3Fe(CN)6 results in disappearance of the 474/480 nm band. Extraction of the prosthetic group then yields only the two N phenylprotoporphyrin IX regioisomers with the N-phenyl group on pyrrole rings A and D. The same regioisomer pattern is obtained if the cytochrome P450IA1 phenyl iron complex is simply warmed to 37 degrees C, but this thermal rearrangement occurs much less readily, if at all, with the complexes of the other isozymes. The regioisomers with the N-phenyl on pyrrole rings A and D are obtained in a 2:1 ratio with isozyme IA1, 1:1 with IIB2, 1:1.7 with IIB1, and 1:2 with IIE1. These results establish that the active sites of these cytochrome P450 isozymes have a common architecture despite their gross differences in substrate specificity. In this architecture, the region directly above pyrrole rings A and D is relatively open whereas that above pyrrole rings B and C is occluded by protein residues. PMID- 1918044 TI - Electron transfer associated with oxygen activation in the B2 protein of ribonucleotide reductase from Escherichia coli. AB - Each of the two beta peptides which comprise the B2 protein of Escherichia coli ribonucleotide reductase (RRB2) possesses a nonheme dinuclear iron cluster and a tyrosine residue at position 122. The oxidized form of the protein contains all high spin ferric iron and 1.0-1.4 tyrosyl radicals per RRB2 protein. In order to define the stoichiometry of in vitro dioxygen reduction catalyzed by fully reduced RRB2 we have quantified the reactants and products in the aerobic addition of Fe(II) to metal-free RRB2apo utilizing an oxygraph to quantify oxygen consumption, electron paramagnetic resonance to measure tyrosine radical generation, and Mossbauer spectroscopy to determine the extent of iron oxidation. Our data indicate that 3.1 Fe(II) and 0.8 Tyr122 are oxidized per mol of O2 reduced. Mossbauer experiments indicate that less than 8% of the iron is bound as mononuclear high spin Fe(III). Further, the aerobic addition of substoichiometric amounts of 57Fe to RRB2apo consistently produces dinuclear clusters, rather than mononuclear Fe(III) species, providing the first direct spectroscopic evidence for the preferential formation of the dinuclear units at the active site. These stoichiometry studies were extended to include the phenylalanine mutant protein (Y122F)RRB2 and show that 3.9 mol-equivalents of Fe(II) are oxidized per mol of O2 consumed. Our stoichiometry data has led us to propose a model for dioxygen activation catalyzed by RRB2 which invokes electron transfer between iron clusters. PMID- 1918045 TI - Mouse submandibular gland prorenin-converting enzyme is a member of glandular kallikrein family. AB - Mouse submandibular gland prorenin-converting enzyme (PRECE) consists of the two polypeptide chains of 17 and 10 kDa and cleaves mouse Ren-2 prorenin at a dibasic site to yield mature renin. Western blot analysis using an antiserum against this enzyme gave rise to multiple bands in mouse submandibular glands, suggesting that PRECE is a member of a protease family. Partial amino acid sequence analysis of purified PRECE and cloning and sequence analyses of its cDNA indicated that it is identical to the mGK-13 gene product, epidermal growth factor-binding protein type B, which is a member of the glandular kallikrein family and is involved in maturation of epidermal growth factor. Conditioned medium from Chinese hamster ovary cells transfected with an expression plasmid for PRECE had prorenin converting activity. These results indicate that PRECE is involved in the maturation of two bioactive polypeptides expressed in mouse submandibular glands, Ren-2 renin and epidermal growth factor. PMID- 1918046 TI - Ligand size as a determinant for catabolism by the low density lipoprotein (LDL) receptor pathway. A lattice model for LDL binding. AB - Low density lipoproteins (LDL) are large (Mr = 2.5 x 10(6)) in comparison to LDL receptors (Mr = 115,000). Since most LDL receptors are clustered in coated pits, we tested the hypothesis that crowding of receptor-bound LDL particles would cause steric effects. The apparent affinity of LDL for receptors on cultured fibroblasts decreased near saturation causing concave-upward Scatchard plots. Both the higher and lower affinity components of binding were up-regulated by the cholesterol synthesis inhibitor, lovastatin, indicating that the entire binding curve was sterol-responsive. In contrast, neither component of LDL binding was present on lovastatin-treated or untreated null fibroblasts which are incapable of expressing LDL receptors. Therefore, the concave-upward Scatchard plots were entirely due to binding to LDL receptors. These results are consistent with a lattice model in which receptor-bound LDL are large enough to decrease binding to adjacent receptors. A lattice model implies that large LDL should produce steric effects at a lower receptor occupancy than should small LDL. This was tested using seven LDL fractions that differed in diameter from 20 to 27 nm. Fewer large than small LDL were bound to the cell surface at 4 degrees C and 37 degrees C, and fewer were internalized and degraded at 37 degrees C. Since large LDL bound via both apolipoprotein (apo) E and apoB100, receptor cross-linking could have caused fewer large LDL to be bound at saturation. However, when the potential for cross-linking was prevented by an apo-E-specific monoclonal antibody (1D7), the difference in binding by large versus small LDL was not eliminated; instead, it was exaggerated. Taken together, these results support a lattice model for LDL binding and indicate that steric hindrance associated with crowding of LDL particles on receptor lattices is a major determinant for catabolism by the LDL receptor pathway in vitro. PMID- 1918047 TI - The structural basis for pyocin resistance in Neisseria gonorrhoeae lipooligosaccharides. AB - Pyocin resistance in a strain of Neisseria gonorrhoeae has been found to be associated with structural differences in the oligosaccharide moieties of the gonococcal outer membrane lipooligosaccharides (LOS). N. gonorrhoeae strain 1291 had been treated with several pyocins, usually lethal bacteriocins produced by Pseudomonas aeruginosa, and a series of surviving mutants were selected. The LOS of these pyocin-resistant mutants had altered electrophoretic mobilities in sodium dodecyl sulfate-polyacrylamide gels (Dudas, K. C., and Apicella, M. A. (1988) Infect. Immun. 56, 499-504). Structural analyses of the oligosaccharide portions of the wild-type (1291 wt) and five pyocin-resistant strains (1291a-e) by liquid secondary ion mass spectrometry, tandem mass spectrometry, and methylation analysis revealed that four of the mutant strains make oligosaccharides that differ from the wild-type LOS by successive saccharide deletions (1291a,c-e) and, in the oligosaccharide of 1291b, by the addition of a terminal Gal to the 1291c structure. The composition, sequence, and linkages of the terminal tetrasaccharide of the wild-type LOS are the same as the lacto-N neotetraose terminus of the human paragloboside (Gal beta 1----4GlcNAc beta 1--- 3Gal beta 1----4Glc-ceramide), and both glycolipids bound the same monoclonal antibodies O6B4/3F11 that recognize this terminal epitope. None of the pyocin resistant mutants bound this antibody. The 1291b LOS bound a monoclonal antibody that is specific for Gal alpha 1----4Gal beta 1----4Glc-ceramide (Pk glycosphingolipid) and shared a common composition, sequence, and linkages with this latter glycosphingolipid. Organisms that bound the anti-Pk monoclone occurred at the rate of approximately 1/750 among the wild-type parent strain. This structural information supports the conclusion that treatment with pyocin selects for mutants with truncated LOS structures and suggests that the oligosaccharides contained in the LOS of the wild-type strain and 1291b mimic those of human glycosphingolipids. PMID- 1918048 TI - Clostridium botulinum C3 ADP-ribosyltransferase gene. Cloning, sequencing, and expression of a functional protein in Escherichia coli. AB - C3 ADP-ribosyltransferase is an exoenzyme produced by certain strains of Clostridium botulinum types C and D, which specifically ADP-ribosylates rho and rac proteins in eukaryotic cells. The enzyme was purified from a culture filtrate of C. botulinum type C strain 003-9, and the amino acid sequence from the amino terminal Ser to Asn192 was determined by Edman degradation. Using a set of degenerate primers based on the sequence, we amplified a part of the gene for this enzyme by polymerase chain reaction. A 2.1-kilobase pair HincII fragment of C. botulinum DNA containing the whole structural gene was then identified by Southern analysis with the polymerase chain reaction product as a probe, and the complete nucleotide structure of the gene together with flanking regions was determined by cloning and DNA sequencing the HincII fragment. The gene encodes a protein of 244 amino acids with a Mr of 27,362 which begins with a putative signal peptide of 40 amino acids. Escherichia coli carrying this gene produced the active enzyme, and about 60% of it was found in the culture medium. Immunoblot analysis with antiserum against the enzyme revealed the presence of two immunoreactive proteins of 27 and 23 kDa in the cytoplasmic/membrane fraction and only the 23-kDa protein in the periplasm and the medium, suggesting that the enzyme expressed is processed in the E. coli, exported into the periplasm and released into the culture medium. PMID- 1918050 TI - Peroxide modification of monoalkylated glutathione reductase. Stabilization of an active-site cysteine-sulfenic acid. AB - Hydrogen peroxide reacts with two-electron reduced glutathione reductase (GR EH2 species) to give the native oxidized enzyme (E) without detectable intermediates. Prior alkylation of the EH2 interchange thiol with iodoacetamide, however, dramatically changes both the course and overall rate of the peroxide reaction. This oxidation, monitored spectrally, is characterized by an intermediate (EHRint) with enhanced long wavelength absorbance extending to 800 nm. This species decays in a second peroxide-dependent phase to an enzyme form (EHRox) easily distinguished from E. Quenching experiments with catalase allow the isolation of a stable mixture consisting of 36% monoalkylated GR (EHR), 60% EHRint, and 4% EHRox; NADPH titration and anaerobic dithiothreitol addition lead to quantitative reduction of EHRint to EHR, and there is an increase in thiol titer of 0.8-SH/FAD on NADPH reduction. Of the four titratable thiols present in EHR, 2.7 are lost on oxidation to EHRox and 0.7-0.8 mol of cysteic acid/FAD is formed. On the basis of these and other observations, we conclude that alkylation of the EH2 interchange thiol, which blocks disulfide formation, allows peroxide reaction at the remaining charge-transfer thiol to proceed via a stabilized cysteine-sulfenic acid intermediate (EHRint), which undergoes further oxidation to the corresponding cysteic acid (EHRox). PMID- 1918049 TI - The yeast general transcription factor TFIIA is composed of two polypeptide subunits. AB - The general transcription factor TFIIA was purified from yeast. A key step in the purification was affinity chromatography using a column containing the adenovirus major late promoter with bound recombinant TFIID to which TFIIA binds with high affinity. TFIIA activity copurifies with two polypeptides of molecular mass 32 and 13.5 kDa. Elution and renaturation of these two polypeptides from sodium dodecyl sulfate-polyacrylamide gels showed that both polypeptides were required for TFIIA activity. TFIIA activity was measured by both a native gel shift assay and by in vitro complementation of transcription using yeast nuclear extracts depleted of TFIIA. The purified renatured yeast TFIIA also complements basal level transcription using a mammalian transcription system depleted of TFIIA. Native TFIIA has an apparent molecular mass of approximately 90 kDa measured by gel filtration chromatography. TFIIA binds to a TFIID.TATA element.DNA complex with an apparent equilibrium dissociation constant (KD) of 20 pM. This affinity is about 100-fold greater than the affinity of TFIID for TATA elements and much greater than the affinity of TFIIA for TFIID not bound to DNA. PMID- 1918052 TI - Nitric oxide production by cultured aortic endothelial cells in response to thiol depletion and replenishment. AB - The requirements and influence of thiols on the production of nitric oxide (NO) were examined in cultured porcine aortic endothelial cells. NO production was diminished when cells were pretreated with thiol-depleting agents (IC50: N ethylmaleimide, 30 microM; 1-chloro-2,4-dinitrobenzene, 200 microM; diamide, 1.5 mM; diethyl maleate, 20 mM). The depletion of glutathione (45-99% loss at the various IC50 values) and protein thiols (3-25% loss at IC50) showed no consistent relationship to decreased NO production. The effects of the agents on NO production were not linked to altered sensitivity to the stimulant (calcium ionophore A23187; maximal effect at 10 microM), but roughly paralleled the appearance of cell damage (17-44% lactate dehydrogenase release at IC50). The decrease in NO production due to 1-chloro-2,4-dinitrobenzene was partially reversed by cysteine, dithioerythritol, and dihydrolipoate, whereas cystine partially reversed the decrease due to diamide or diethyl maleate. On the other hand, several thiols diminished NO production in control cells. Overall, alterations of NO production did not parallel the depletion or replenishment of either glutathione, protein thiol, or soluble thiol pools, and so the results argue against hypotheses that cellular thiols are either substrates or necessary cofactors in the pathway of NO synthesis in endothelial cells. PMID- 1918051 TI - Role of the invariant aspartic acid 99 of human choriogonadotropin beta in receptor binding and biological activity. AB - The four human glycoprotein hormones are heterodimers that contain a common alpha subunit and a hormone-specific beta subunit. Within this hormone family, 23 amino acid sequences from 11 mammalian species are available. There are 19 invariant amino acid residues in the beta subunits, 12 of which are Cys that form six disulfide bonds. Of the remaining seven conserved amino acid residues, we have investigated the role of an Asp which occurs at position 99 in human choriogonadotropin beta (hCG beta). Site-directed mutagenesis was used to replace hCG beta Asp99 with three residues, Glu, Asn, and Arg, and to prepare an inversion double mutant protein, Arg94----Asp and Asp99----Arg. The cDNAs were placed in a eukaryotic expression vector, and the plasmids were transiently transfected into Chinese hamster ovary cells containing a stably integrated gene for bovine alpha. Radioimmunoassays demonstrated that the mutant forms of hCG beta were capable of subunit assembly to the same extent as hCG beta wild type. The heterologous heterodimers were assayed in vitro using transformed mouse Leydig cells (MA-10) by competitive inhibition of 125I-hCG binding and stimulation of progesterone production. The gonadotropins containing Glu and Asn were active, although the potency was less than that associated with the hCG beta wild type-containing gonadotropin. In contrast, the Arg99-containing mutant protein and the inversion mutant protein Asp94/Arg99 were devoid of activity. Thus, in hCG beta Asp99 can be substituted with certain residues without total loss of function, although replacement with a positively charged residue leads to an inactive heterodimer. The primary role of Asp99 in hCG beta seems to involve, either directly or indirectly, receptor recognition. PMID- 1918053 TI - 1H NMR and CD secondary structure analysis of cell adhesion promoting peptide F-9 from laminin. AB - A heparin binding, cell adhesion promoting domain, termed peptide F-9, from the B1 chain of human laminin, residues 641 to 660, i.e. RYVVLPRPVCFEKGMNYTVR, has been investigated by 1H NMR (500 MHz) spectroscopy and CD spectropolarimetry. While small linear peptides in water solution normally exist in a number of fluctuating conformational states, CD data analysis of peptide F9 indicates the existence of some preferred average structural populations consisting of about 30% beta-sheet, 22% beta-turn, and 6% alpha-helix. NMR structural analysis supports this observation and indicates specific sequences of preferred structural populations. Evidence for these is indicated by the presence of dNN nuclear Overhauser effect (NOE) populations and attenuated or absent d alpha N NOEs at short mixing times (0.1 s), 3J alpha N coupling constants of 5 and 10 Hz, and chemical shifts significantly removed from random coil positions. The NH2 terminal VVL sequence primarily exists in an extended chain conformation by virtue of large d alpha N NOEs and 9-10 Hz 3J alpha N coupling constants. Residues C10-N16 have turn-like or helix character with a run of dNN and d beta N NOEs and attenuated d alpha N NOEs. These midchain reversals include the lysine and asparagine residues proposed to be involved in heparin binding and N glycosylation, respectively, to laminin peptide F-9. PMID- 1918054 TI - Gene expression by a hypovirulence-associated virus of the chestnut blight fungus involves two papain-like protease activities. Essential residues and cleavage site requirements for p48 autoproteolysis. AB - Proteolytic processing plays a fundamental role in gene expression of a recently characterized viral-like double-stranded RNA associated with biological control of the chestnut blight fungus. Polypeptide p29, a papain-like protease, was shown to autocatalytically release itself from the NH2 terminus of the polyprotein specified by the first of two encoded open reading frames, ORF A (Choi, G. H., Shapira, R., and Nuss, D. L. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1167-1171; Choi, G. H., Pawlyk, D. M., and Nuss, D. L. (1991) Virology 183, 747-752). The characterization of a second autocatalytic protease, p48, which is encoded by ORF B, is the subject of this report. Deletion analysis revealed that the catalytic domain resides within the carboxyl-terminal region, while site-specific mutational analysis identified Cys-341 and His-388 as residues essential for autoproteolysis. Autoproteolytic processing by p48 was also demonstrated when expressed in Escherichia coli and microsequence analysis of the recovered COOH terminal cleavage product indicated that cleavage occurred between Gly-418 and Ala-419. The requirements for a functional cleavage site, including confirmation of the cleavage dipeptide, were defined by amino acid substitution analysis. Similarities between p29 and p48 suggest that the respective coding domains could have arisen as a result of a gene duplication event. PMID- 1918055 TI - Follistatin, an activin-binding protein, associates with heparan sulfate chains of proteoglycans on follicular granulosa cells. AB - Follistatin, an activin-binding protein secreted by cultured rat granulosa cells, was shown to associate with the cell surface by affinity labeling with 125I activin. Addition of follistatin to the cultured cells demonstrated a typical ligand-binding saturation curve, suggesting that granulosa cells have a specific binding site for follistatin. This binding was markedly inhibited by heparin and heparan sulfate, but not by chondroitin sulfates A and C, keratan sulfate, and dermatan sulfate. When granulosa cells were treated with glycosaminoglycan degrading enzymes before or after addition of follistatin to the cultures, heparinase and heparitinase treatments resulted in significant suppression of the binding, whereas treatment with chondroitinase ABC had no effect. A competition study of the binding using heparin derivatives demonstrated that follistatin seemed to recognize O-sulfate groups in the heparin molecule. Heparitinase treated granulosa cells exhibited almost full responsiveness to activin, indicating that the enzyme treatment had no effect on activin and receptor interaction. These results suggest that follistatin/activin-binding protein binds to heparan sulfate side chains of proteoglycans on the granulosa cell surface to regulate the various actions of activin. PMID- 1918056 TI - Evidence that erythroid-type glucose transporter intrinsic activity is modulated by cadmium treatment of mouse 3T3-L1 cells. AB - Previous studies suggest that regulation of hexose uptake in Chinese hamster ovary fibroblasts can occur by alterations in glucose transporter intrinsic activity without changes in cell surface transporter number (Harrison, S. A., Buxton, J. M., Helgerson, A. L., MacDonald, R. G., Chlapowski, F. J., Carruthers, A., and Czech, M. P. (1990) J. Biol. Chem. 265, 5793-5801). We tested this hypothesis using 3T3-L1 fibroblasts and adipocytes which exhibit 5-6-fold increases in 2-deoxyglucose or 3-O-methylglucose uptake when exposed to low micromolar concentrations of cadmium for 18 h. Cadmium treatment decreased the apparent Km of 3T3-L1 fibroblasts for 3-O-methylglucose influx from approximately 28 to 9 mM and increased the apparent Vmax by 2-3-fold. These fibroblasts lack the skeletal muscle/adipocyte-type (GLUT4) transporter and showed only a small increase in total cellular immunoreactive HepG2 type (GLUT1) transporter in response to cadmium. Furthermore, cell surface GLUT1 levels did not change in 3T3 L1 fibroblasts exposed to cadmium, as assessed by the binding to intact cells of an antibody which recognizes an extracellular GLUT1 epitope. Insulin enhanced 2 deoxyglucose uptake 2-fold in 3T3-L1 fibroblasts, but did not further stimulate cadmium-activated transport rates. In contrast, insulin stimulated hexose transport 15-fold in 3T3-L1 adipocytes, which express both GLUT1 and GLUT4 proteins, and this effect was fully additive with the 5-fold effect of cadmium. Cadmium had little or no effect on immunoreactive GLUT1 or GLUT4 in isolated 3T3 L1 adipocyte plasma membranes. In contrast, insulin action led to marked recruitment (3-fold) of GLUT4 to the plasma membrane fraction in adipocytes treated with or without cadmium. Taken together, these data are consistent with the hypothesis that cadmium-activated sugar uptake is catalyzed by GLUT1, whereas insulin-stimulated sugar uptake is catalyzed predominantly by GLUT4 in 3T3-L1 adipocytes. Furthermore, the data suggest that the GLUT1 transporter can undergo significant increases in intrinsic catalytic activity in response to cadmium treatment of 3T3-L1 fibroblasts and adipocytes. PMID- 1918057 TI - The malZ gene of Escherichia coli, a member of the maltose regulon, encodes a maltodextrin glucosidase. AB - We have characterized a maltodextrin glucosidase, previously described as a maltose-inducible, cytoplasmic enzyme that cleaves p-nitrophenyl-alpha-maltoside in Escherichia coli. The gene encoding the enzyme activity, referred to as malZ, is located at 9.3 min on the chromosomal map. We cloned the gene in a high copy number vector and purified the enzyme. It is a monomer, with an apparent molecular weight of 65,000. The enzyme degrades maltodextrins, ranging from maltotriose to maltoheptaose, to shorter oligosaccharides, the final hydrolysis products being maltose and glucose. We measured the kinetic parameters, Km and Vmax, for the hydrolysis to glucose of the five different substrates. The binding of the substrate is enhanced by increasing the number of glucosyl residues in the maltodextrin. In contrast, the maximum rate of hydrolysis (Vmax) is fastest for maltotriose. To study the mode of action of the enzyme, we quantitatively measured the amount of free glucose liberated from the different maltodextrin substrates after a long incubation. More glucose is liberated from the long dextrins, as compared to the shorter ones, showing that the primary hydrolysis product was glucose, not maltose. Furthermore, [14C]maltotriose, specifically labeled at the reducing end, was hydrolyzed to [14C]glucose and unlabeled maltose. These data demonstrate that the malZ gene product is a maltodextrin glucosidase, liberating glucose from the reducing end of malto-oligosaccharides. The nucleotide sequence of malZ and the deduced amino acid sequence showed that malZ encodes a protein with a molecular weight of 68,960. Homology to glucosidases, alpha-amylases, and pullulanases were observed. Conserved regions thought to represent active sites in dextrin hydrolases were found in the MalZ protein. PMID- 1918058 TI - Are the histidine residues of glutathione S-transferase important in catalysis? An assessment by 13C NMR spectroscopy and site-specific mutagenesis. AB - To test the proposition that a histidine residue is essential in the catalytic mechanism of glutathione S-transferase, rat liver isoenzyme 3-3 specifically labeled with [ring-2-13C]histidine was prepared. The 13C NMR spectrum of the labeled enzyme revealed four resonances corresponding to the 4 histidine residues in the mu gene class type 3 subunit. Titration of the four resonances in the range of pH 4-9 both in the presence and absence of glutathione gave pK alpha values of much less than 4, 5.2, 7.1, and 7.8 for the four side chains that were identified by site-specific mutagenesis as His14, His83, His84, and His167, respectively. The magnetic resonance properties and titration behavior of His14 suggest that this residue is buried in a hydrophobic environment. Conservative replacement of each histidine with asparagine results in mutant enzymes that have catalytic properties very close to the native protein as assessed with three different substrates, 1-chloro-2,4-dinitrobenzene, 4-phenyl-3-buten-2-one, and phenanthrene 9,10-oxide. The results indicate clearly that none of the histidine residues of isoenzyme 3-3 is essential for stabilization of the bound glutathione thiolate or for any other aspect of catalysis. PMID- 1918059 TI - The primary structure of Aspergillus niger acid proteinase A. AB - The complete amino acid sequence of the acid proteinase A, a non-pepsin type acid proteinase from the fungus Aspergillus niger var. macrosporus, was determined by protein sequencing. The enzyme was first dissociated at pH 8.5 into a light (L) chain and a heavy (H) chain, and the L chain was sequenced completely. Further sequencing was performed with the reduced and pyridylethylated or aminoethylated derivative of the whole protein, using peptides obtained by digestions with Staphylococcus aureus V8 protease, trypsin, chymotrypsin, and lysylendopeptidase. The location of the two disulfide bonds was determined by analysis of cystine containing peptides obtained from a chymotryptic digest of the unmodified protein. These results established that the protein consists of a 39-residue L chain and a 173-residue H chain that associate noncovalently to form the native enzyme of 212 residues (Mr 22,265). This is, to our knowledge, the first time that such a protein with a rather short peptide chain associated noncovalently has been found. No sequence homology is found with other acid or aspartic proteinases, except for Scytalidium lignicolum acid proteinase B, an enzyme unrelated to pepsin by sequence, which has about 50% identity with the present enzyme. These two enzymes, however, are remarkably different from each other in some structural features. PMID- 1918060 TI - The gene and deduced protein sequences of the zymogen of Aspergillus niger acid proteinase A. AB - Proteinase A obtained from the culture medium of Aspergillus niger var. macrosporus is a unique acid endopeptidase that is insensitive (or less sensitive) to specific inhibitors of ordinary acid or aspartic proteinases, such as pepstatin, diazoacetyl-DL-norleucine methyl ester, and 1,2-epoxy-3-(p nitrophenoxy)-propane. In the preceding paper (Takahashi, K., Inoue, H., Sakai, K., Kohama, T., Kitahara, S., Takishima, K., Tanji, M., Athauda, S. B. P., Takahashi, T., Akanuma, H., Mamiya, G., Yamasaki, M. J. Biol. Chem. 266, 19480 19483), we reported the complete primary structure of the mature enzyme determined at the protein level. The enzyme has a unique two-chain structure with a 39-residue light (L) chain and a 173-residue heavy (H) chain linked noncovalently. As an extension of this study, we isolated genomic and cDNA clones encoding this proteinase and determined their nucleotide sequences. To isolate a genomic clone, the genomic DNA was selectively amplified by polymerase chain reaction using mixed oligonucleotide primers designed from the amino acid sequence of the H chain, and a specific probe thus generated was used for screening a lambda gt10 genomic library. A cDNA for the enzyme was also selectively amplified by polymerase chain reaction using primers synthesized based on the sequence of the genomic DNA. Sequencing of the cloned genomic DNA and cDNA revealed the nucleotide sequence of the structural gene for the enzyme of 846 base pairs without introns. It encodes the precursor form of proteinase A, including an NH2-terminal preprosequence of 59 residues, the L chain of 39 residues, an intervening sequence of 11 residues, and the H chain of 173 residues linked in that order. Thus, proteinase A is thought to be synthesized as a single peptide chain preproenzyme of 282 residues, which is processed to generate the mature two-chain form. PMID- 1918061 TI - Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. AB - Lipopolysaccharide (LPS) endotoxin is implicated as the bacterial product responsible for the clinical syndrome of Gram-negative septicemia. Although the lipid A domain of LPS appears to be responsible for the toxicity of endotoxin, lipid A from the photosynthetic bacterium Rhodobacter sphaeroides (RSLA) and a disaccharide precursor of lipid A from enteric bacteria, termed lipid IVA, have little activity on human cells. Using the human promonomyelocytic cell line THP-1 and human monocytic cells, we now show that both lipid IVA and RSLA are antagonists of LPS. Complete, apparently competitive, inhibition of LPS activity is possible at a 10-100-fold excess of antagonist, as judged by measuring the release of cytokines and prostaglandin E2. Both antagonists prevent monocyte stimulation by endotoxin extracted from a variety of Gram-negative bacteria. Cells pretreated with either inhibitor and subsequently washed still show attenuated responses to LPS. Stimulation of monocytes by whole Gram-negative bacteria is also antagonized in a dose-dependent manner. Lipid X has no inhibitory effect in the same dose range as lipid IVA and RSLA. These findings rule out LPS sequestration as the explanation for the observed antagonism. Neither inhibitor alters monocyte stimulation by phorbol 12-myristate 13-acetate, Staphylococcus aureus, or purified protein derivative, demonstrating specificity for LPS. Although RSLA appears to inhibit LPS when tested with macrophages from both humans and mice, lipid IVA had the unique ability to act as an LPS antagonist with human-derived cells but to exhibit LPS-like effects with murine derived cells. Like LPS, lipid IVA stimulated the release of both tumor necrosis factor alpha and arachidonic acid from murine-derived RAW 264.7 macrophage tumor cells. The range of concentrations necessary for lipid IVA to induce LPS-like effects in murine cells was similar to that necessary to antagonize the actions of LPS in human monocytes. The agonist activities of lipid IVA were completely inhibitable by RSLA. This unique species-dependent pharmacology observed with lipid IVA may reflect differences between human and murine LPS receptors. RSLA and lipid IVA may be useful in defining the role of LPS in Gram-negative bacterial infections and may prove to be prototypical therapeutic agents for the treatment of Gram-negative septicemia. PMID- 1918062 TI - Macrophage catabolism of lipid A is regulated by endotoxin stimulation. AB - Lipopolysaccharide (LPS) is a Gram-negative bacterial glycolipid that is believed to cause, by virtue of its stimulatory actions on macrophages and other eukaryotic cells, the life-threatening symptoms associated with Gram-negative infections. Macrophages both respond to and catabolically deactivate LPS. The lipid A moiety of LPS is responsible for the stimulatory actions of LPS on macrophages. We have previously developed methods employing a radiolabeled bioactive lipid A precursor, 4'-32P-lipid IVA, to study the interaction of this class of lipids with animal cells (Hampton, R. Y., Golenbock, D. T., and Raetz, C. R. H. (1988). J. Biol. Chem. 263, 14802-14807). In the current work, we have examined the uptake and catabolism of 4'-32P-lipid IVA by the RAW 264.7 cell line in serum-containing medium at physiological temperatures and have studied the effect of LPS stimulation on the ability of these cells to catabolize lipid IVA. RAW 264.7 macrophage-like cells avidly take up 4'-32P-lipid IVA under cell culture conditions at nanomolar concentrations. Uptake of lipid IVA was accompanied by lysosomal dephosphorylation of a fraction of the lipid to yield 4' monophosphoryl lipid IVA. Chemically generated 4'-monophosphoryl lipid IVA was found to be substantially less bioactive than lipid IVA in the RAW cell, indicating that this catabolic dephosphorylation results in detoxification. In uptake experiments of 3-4 h duration, all metabolism of lipid IVA is blocked by ligands of the macrophage scavenger receptor. In longer experiments (24 h), both scavenger receptor-dependent and -independent uptake are responsible for the lysosomal catabolism of lipid IVA. Preincubation of RAW 264.7 cells with LPS caused dose-dependent inhibition of lipid IVA dephosphorylation. Sufficient LPS stimulation resulted in essentially complete inhibition of lipid IVA catabolism in both short- and long-term uptake experiments. This effect occurred at physiologically relevant concentrations of LPS (IC50 less than 1 ng/ml), and our data indicate that LPS-induced blockade of lipid IVA catabolism was due to the resultant physiological stimulation of the cells, and not inhibition of dephosphorylation by competition for uptake or enzymatic sites or by simple sequestration of labeled lipid IVA by LPS aggregates. We suggest that in the macrophage, LPS can modulate its own catabolism by virtue of its pharmacological properties. This effect of LPS could play a role in LPS pathophysiology as well as in macrophage biology. PMID- 1918063 TI - Purification of the alternative sigma factor, sigma 54, from Salmonella typhimurium and characterization of sigma 54-holoenzyme. AB - The alternative sigma factor sigma 54 of enteric bacteria, or its homologue in other purple bacteria, is required for transcription of genes whose products have diverse physiological roles. Previous studies have indicated that sigma 54 confers on core RNA polymerase the ability to recognize a specific class of promoters but not the ability to isomerize from closed to open complexes. Isomerization requires ATP and one member of a family of activator proteins, it being different activator proteins that allow this form of polymerase to respond to different physiological signals. We have developed a strategy for overproducing and purifying sigma 54 from Salmonella typhimurium and have studied several biochemical properties of reconstituted sigma 54-holoenzyme. The initial binding constant KB for the formation of closed complexes between this holoenzyme and the ginA promoter in our transcription buffer is approximately 3 x 10(8) M-1, which was determined from DNaseI protection assays at 37 degrees C. After the formation of open complexes, several properties of sigma 54-holoenzyme appear to be similar to those of sigma 70-holoenzyme. We have determined the complete nucleotide sequence of the gene encoding sigma 54 (ntrA) in Salmonella. PMID- 1918064 TI - Biochemical and ultrastructural evidence for the association of basic fibroblast growth factor with cardiac gap junctions. AB - Basic fibroblast growth factor (bFGF) is a ubiquitous and multifunctional polypeptide that is believed to have a role in tissue repair and to act as a morphogen in embryonic development. Here, we have used immunohistochemical and biochemical methods with antibodies directed against the amino-terminal domain of bFGF, designated IS2, which recognize native and denatured bFGF, to demonstrate that in addition to its known intracellular and extracellular localization in heart, bFGF is also associated with cardiomyocyte gap junctions. In tissue sections, IS2 labeled regions of intercalated discs, producing an immunofluorescence pattern virtually indistinguishable from that obtained with antibodies against the heart gap junction protein connexin-43. By electron microscopy, gap junctions but not other regions of plasma membrane were heavily immunolabeled with this antibody. By solid phase immunoassay, bFGF was found to be more concentrated in a fraction enriched in cardiac gap junctions than in whole sarcolemmal preparations. Finally, an 18-kDa protein was recognized by several different antibodies specific for bFGF on Western blots of heart subcellular fractions enriched in gap junctions. We suggest that bFGF-like peptides are either an integral part of, or exist in close association with, cardiac gap junctions and thus may play a role in modulating gap junctional intercellular communication. PMID- 1918065 TI - In vitro transcriptional analysis of the human c-fos proto-oncogene. AB - The transcription of the human c-fos promoter was characterized in vitro using HeLa nuclear and whole cell extracts. The c-fos gene and c-fos promoter fusions to the SV40 early region and the G-free cassette were active as templates, yielding faithfully initiated transcripts that were sensitive to alpha-amanitin. c-fos-SV40 and -G-free cassette templates were less efficiently transcribed when linearized, suggesting that template topology affected fos activity in vitro. Transcription conditions were optimized for both extracts using a mixture of the fos wild type promoter, a deleted fos promoter retaining just the TATA box, and the adenovirus major late promoter, all driving differently sized G-free cassettes. The fos promoter was inactive at low protein and DNA concentrations, and then showed a sharp rise in efficiency with a subsequent 2-fold increase in the amount of either DNA or protein. In contrast, high protein or DNA concentrations were required for the deleted fos promoter to show only weak activity. Preincubation of templates with extracts shortened the lag time before transcription could be detected, but did not lead to increased activity. By comparing reactions in the presence and absence of Sarkosyl, we estimate that only a subset of fos-driven templates was active, and that these templates were used for several rounds of transcription. PMID- 1918067 TI - SSR alpha and associated calnexin are major calcium binding proteins of the endoplasmic reticulum membrane. AB - GTP phosphorylation of rough microsomes in vitro is limited to four integral membrane proteins. Two of these, a phosphoprotein (pp90) and a phosphoglycoprotein (pgp35) were purified as a complex with two nonphosphorylated membrane glycoproteins, gp25H and gp25L. The authenticity of this complex was confirmed using two different purification procedures and by coimmunoprecipitation. By immunofluorescence a reticulated cytoplasmic network was revealed for the proteins which was similar to that for Louvard et al. (Louvard, D., Reggio, H., and Warren, G. (1982) J. Cell Biol. 92, 92-107) marker antisera which also recognized purified pp90 on immunoblots. Amino acid sequencing of peptides derived from pgp35 identified this protein as SSR alpha, an endoplasmic reticulum constituent as identified by cross-linking of translocating nascent chains (Gorlich, D, Prehn, S., Hartmann, E., Herz, J., Otto, A., Kraft, R., Wiedmann, M., Knespel, S., Dobberstein, B., and Rapoport, T. A. (1990) J. Cell Biol. 111, 2283-2294). The sequence of gp25H was determined from cDNA clones and was identical with SSR beta identified by Gorlich et al. (1990) as being tightly bound to SSR alpha. Sequencing of gp25L revealed no similarity of the deduced sequence with other proteins. However, pp90 revealed a high degree of sequence identity with the Ca(2+)-binding protein, calreticulin. 45Ca2+ overlay studies indicated that pp90 bound Ca2+ and the name calnexin is proposed. Surprisingly, pgp25 (SSR alpha) also bound Ca2+ although gp25H (SSR beta) and gp25L did not. Triton X-114 partitioning of the integral membrane proteins of rough microsomes suggested that pgp35 (SSR alpha) and calnexin were major Ca(2+)-binding proteins of the endoplasmic reticulum membrane. We propose that the function of the complex is to regulate Ca(2+)-dependent retention mechanisms for luminal proteins of the endoplasmic reticulum. PMID- 1918066 TI - Coupled transcription-polyadenylation in a cell-free system. AB - To investigate the relationship between transcription and polyadenylation, an in vitro system has been developed in which endogenously transcribed pre-mRNAs containing functional polyadenylation sites are rapidly and accurately cleaved in a HeLa nuclear extract. Cleavage of endogenously transcribed substrates differed from that of exogenous substrates in that a proximal 3' terminus was not required, the reaction was more tolerant of increased Mg2+ levels, and endogenous substrates were cleaved more efficiently. A promoter dependence for this reaction was suggested by the observation that substrates transcribed by bacteriophage T7 RNA polymerase in the presence of nuclear extract were not cleaved. In addition, analysis of the bovine growth hormone poly(A) site indicated that it is highly efficient in vitro which agrees with previous in vivo data. The availability of an in vitro system in which transcription and polyadenylation are coupled should facilitate analysis of the relation between 3' end processing and RNA polymerase II transcription termination as well as the promoter requirements for polyadenylation. PMID- 1918068 TI - Interleukin-8 gene expression in human bronchial epithelial cells. AB - The capacity of cells of the human bronchial epithelium to express the gene for interleukin-8 (IL-8) was evaluated in bronchial epithelium derived cell lines, HS 24 and BET-1A, using tumor necrosis factor-alpha (TNF) as a model inflammatory stimulus. As in other epithelium, TNF markedly increased the level of the 1.8 kilobase IL-8 mRNA transcripts in both bronchial epithelial cell lines. In HS-24 cells, nuclear run-on analyses showed the IL-8 gene transcription rate was dramatically increased, more than 30-fold, after TNF stimulation. The half-life of IL-8 mRNA transcripts in these cells was approximately 40 min and did not change after TNF stimulation, suggesting that TNF up-regulated IL-8 gene expression mainly at the transcriptional level. DNase I hypersensitivity site mapping of chromatin DNA in resting HS-24 cells demonstrated two hypersensitivity sites within 400 base pairs (bp) 5' to exon I and one site within exon I. However, after TNF stimulation, the exon I hypersensitivity site disappeared and a new site approximately 120 bp 5' to exon I emerged. Consistent with these observations, transfection studies with HS-24 cells using fusion genes composed of the 5'-flanking sequences of the IL-8 gene and a luciferase reporter gene demonstrated potent promoter activity in a 174-bp segment (-130 to +44 relative to the transcription start site), which also exhibited a response to TNF, while a segment from -112 to +44 showed very low promoter activity and no response to TNF. Thus, human bronchial epithelial cells can express the IL-8 gene, with expression in response to the inflammatory mediator TNF regulated mainly at the transcriptional level, and with elements within the 5'-flanking region of the gene that are directly or indirectly modulated by the TNF signal. PMID- 1918069 TI - Spectroscopic studies of the structural domains of mammalian DNA beta-polymerase. AB - The 8- and 31-kDa fragments of beta-polymerase, prepared by controlled proteolysis as described (Kumar, A., Widen, S. G., Williams, K. R., Kedar, P., Karpel, R. L., and Wilson, S. H. (1990) J. Biol. Chem. 265, 2124-2131), constitute domains that are structurally and functionally dissimilar. There is little disruption of secondary structure upon proteolysis of the intact enzyme, as suggested from CD spectra of the fragments. beta-Polymerase is capable of binding both single- and double-stranded nucleic acids: the 8-kDa fragment binds specifically to single-stranded lattices, whereas the 31-kDa domain displays affinity exclusively for double-stranded polynucleotides. These domains are connected by a highly flexible protease-hypersensitive segment that may allow the coordinate functioning of the two binding activities in the intact protein. beta Polymerase binds to poly(ethenoadenylic acid) with higher affinity, similar cooperativity, but lesser salt dependence than the 8-kDa fragment. Under physiological conditions, the intact enzyme displays greater binding free energy for single-stranded polynucleotides than the 8-kDa fragment, suggesting that the latter may carry a truncated binding site. Binding of double-stranded calf thymus DNA brings about a moderate quenching of the Tyr and Trp fluorescence emission of both the 31-kDa fragment and beta-polymerase and induces a 6-nm blue shift in the Trp emission maximum of the intact enzyme, but not in the fragment. This latter result is likely due to a change in the relative orientation of the 8- and 31-kDa domains in the intact protein upon interaction with double-stranded DNA; alternatively, the binding mode of intact protein may differ from that of the fragment. Simultaneous interaction of both domains with polynucleotides most likely does not occur since double-stranded DNA binding to the 31-kDa domain of intact beta-polymerase induces the displacement of single-stranded polynucleotides from the 8-kDa domain. These results are evaluated in light of the role of beta-polymerase in DNA repair. PMID- 1918070 TI - Oligomeric binding of T3 receptor is required for maximal T3 response. AB - Receptors in the thyroid-steroid hormone superfamily bind preferentially as dimers to palindromic response elements containing two hexameric half-sites. The 23-base pair rat growth hormone (rGH) T3 response element (T3RE), however, contains three hexameric binding domains, all of which are required for maximal T3 response. We examined the binding of purified T3 receptor alpha (T3R alpha), overexpressed in Escherichia coli, to wild-type and up and down mutations of the rGH T3RE to evaluate whether transcriptional potency correlates with changes in T3R binding. T3R binds to the rGH T3RE as a monomer, dimer, or higher order oligomer. Cooperative T3R dimer binding was demonstrated to two hexameric domains of the rGH T3RE arranged as either direct or inverted repeats. Decreased binding was seen with point mutations in each domain as well as with mutations which altered hexamer orientation and spacing within the site. These results demonstrate that all three hexamers of the rGH T3RE are involved in binding T3R. Occupancy of all three hexamers by T3R in the gel shift assay was observed with functional up mutations of the T3RE, increasing receptor concentration or addition of nuclear extract. The transcriptional response potencies of T3RE up or down mutants in a transient transfection assay correlated closely with T3R binding. These results confirm our earlier hypothesis that all three hexamers of the rGH T3RE bind T3R in a novel binding arrangement and provide a model for the interaction of T3R and other nuclear proteins with the DNA sequences of thyroid hormone-regulated genes. PMID- 1918071 TI - Peptide binding by protein disulfide isomerase, a resident protein of the endoplasmic reticulum lumen. AB - Previously we had demonstrated by photoaffinity labeling that a 57-kDa protein of the endoplasmic reticulum can bind and become covalently linked to glycosylatable photoreactive peptides containing the sequence-Asn-Xaa-Ser/Thr-. Subsequently, it was found that this protein, called glycosylation site-binding protein, was a multifunctional protein, i.e. it was identical to protein disulfide isomerase (PDI), the beta-subunit of prolyl hydroxylase and thyroid hormone-binding protein. In this study, the peptide specificity for binding to this 57-kDa protein, hereafter called PDI, has been investigated in more detail using photoaffinity probes. The results reveal that although N-glycosylation by oligosaccharyl transferase in the endoplasmic reticulum has an absolute requirement for an hydroxyamino acid in the third amino acid residue of the glycosylation site sequence, no such specificity is observed in the binding of such peptides to PDI. In addition to the lack of specificity for an hydroxyamino acid in the third residue position, no specificity was observed for the asparagine residue in the first position. Thus, binding is not restricted to peptides containing N-glycosylation sites. We have investigated the discrepancy between this apparent lack of sequence specificity and earlier results indicating that binding of peptides to PDI was specific for N-glycosylation site sequences. We now demonstrate that PDI in the lumen of microsomes is more efficiently labeled by peptides containing photoreactive-Asn-Xaa-Ser/Thr- sequences than by nonacceptor site sequences because the former become glycosylated. This increased labeling does not occur because the glycosylated form of the probes are preferentially recognized by PDI. Rather, it appears that increased polarity of the affinity probe after attachment of the oligosaccharide chain prevents its exit from the sealed microsomes, in effect concentrating it within the lumen of the microsome. These results, coupled with other studies on the multifunctional nature of PDI, suggest that the observed peptide binding may be a manifestation of the ability of PDI to recognize the backbone of polypeptides in the lumen of the endoplasmic reticulum. PMID- 1918072 TI - Cloning and expression of a divergent integrin subunit beta 8. AB - Rabbit and human cDNA clones have been identified that encode a novel integrin beta subunit. The sequences that encode this subunit, which has been designated as beta 8, were isolated initially from rabbit placental cDNA libraries using an oligonucleotide probe derived from a highly conserved region of integrin beta subunit sequences. The rabbit clone was used to isolate human beta 8 cDNA clones from human placental and MG-63 osteosarcoma cell libraries. The putative beta 8 polypeptides, which comprise 769 and 768 residues in human and rabbit, respectively, show a high degree of inter-species conservation (approximately 90% identity). In contrast, beta 8 is distinct from the other integrin beta subunits. At the amino acid level human beta 8 ranges from 31 to 37% identity with human beta 1-7. The domain structure of beta 8 is typical of the integrin beta subunits. Human beta 8 has a 42-residue N-terminal signal peptide, a large extracellular domain (approximately 639 residues) that contains four cysteine rich repeats, a transmembrane domain (approximately 30 residues), and a C terminal cytoplasmic domain (approximately 58 residues). There are several structural features that are unique to the beta 8 polypeptide, as compared with the other integrin beta subunits. Six of the 56 cysteine residues that are conserved within the extracellular domains of beta 1, beta 2, beta 3, beta 5, beta 6, and the beta subunit from Drosophila are absent in the beta 8 polypeptide. Also, the cytoplasmic domain of the beta 8 subunit shares no homology with the cytoplasmic regions of any of the other integrin beta subunits. Northern analysis demonstrated an approximately 8-kilobase beta 8 mRNA in rabbit placenta, kidney, brain, ovary, and uterus. PCR analysis revealed that beta 8 mRNA is also present in several transformed human cell lines. The beta 8 polypeptide has been transiently expressed in 293 human embryonic kidney cells. A polyclonal antipeptide antibody specific for beta 8 and a polyclonal antibody that recognizes alpha v epitopes were used to show that beta 8 can complex with the endogenous alpha v subunit in 293 cells and that the resulting integrin is expressed as a cell surface complex. PMID- 1918073 TI - Structure and developmental expression of troponin I isoforms. cDNA clone analysis of avian cardiac troponin I mRNA. AB - We isolated avian (chicken and quail) cardiac troponin I (TnIcardiac) cDNA clones for studies of Tn-Icardiac protein structure/evolution and developmental gene regulation. Comparison of the cDNA-predicted avian TnIcardiac amino acid sequences with known TnI sequences indicated 1) that the presence of an N terminal extension sequence carrying a dual protein kinase A phosphorylation target site and an adjacent proline-rich segment is an ancient cardiac-specific feature of TnI which has been conserved since the bird/mammal divergence, 2) that features of the near-N-terminal troponin C (TnC)-binding site sequence suggest isoform-specific adaptation of TnI and TnC, and 3) that the avian TnIcardiac internal actin/TnC-binding, actomyosin-inhibitory, domain shows significant sequence divergence from mammalian TnIcardiac sequences, including the absence of a protein kinase C target site which is a cardiac-specific feature of TnI in mammals. Use of the cDNA clones to probe TnIcardiac mRNA expression during striated muscle development showed active expression in cardiac muscle from early developmental times (day 4 in ovo), but not in embryonic or adult skeletal muscle or in embryonic skeletal muscle cell cultures. Transcriptional run-on analysis showed that the heart-specific expression of TnIcardiac mRNA in embryonic striated muscle reflects transcriptional control of TnIcardiac gene expression. In many other contractile protein gene families, genes encoding cardiac isoforms are expressed early in skeletal muscle development and are later repressed. Thus, the restriction of active TnIcardiac gene expression to the cardiac muscle cell lineage is an unusual expression pattern for cardiac contractile protein genes and indicates that diverse gene regulatory mechanisms direct the differential expression of cardiac and skeletal muscle isoforms in different muscle gene families. PMID- 1918074 TI - Biosynthesis of the cell adhesion molecule uvomorulin (E-cadherin) in Madin-Darby canine kidney epithelial cells. AB - The Ca(2+)-dependent cell adhesion molecule uvomorulin is a transmembrane glycoprotein that functions at the cell surface to regulate epithelial cell recognition and adhesion. We have investigated the temporal and spatial regulation of uvomorulin biosynthesis and cell surface expression in Madin-Darby canine kidney epithelial cells. We show that uvomorulin is synthesized as a precursor polypeptide (Mr 135,000) that is core glycosylated in the endoplasmic reticulum. The precursor is processed to the mature polypeptide (Mr 120,000) shortly after addition of complex carbohydrate groups in the late Golgi complex, but prior to delivery of the polypeptide to the cell surface. However, glycosylation is not required for either efficient processing of the precursor or transport of uvomorulin to the cell surface. At the cell surface, uvomorulin is turned over rapidly (t1/2 approximately 5 h). Induction of Ca(2+)-dependent cell cell contact results in rapid localization of cell surface uvomorulin to regions of contact and an increase in the proportion of uvomorulin that is insoluble in buffers containing Triton X-100. These results indicate several regulatory steps in the biosynthesis and cell surface expression of uvomorulin in epithelial cells. PMID- 1918075 TI - The major alpha-class glutathione S-transferases of rabbit lung and liver. Primary sequences, expression, and regulation. AB - The complete primary structures of two distinct rabbit alpha-class glutathione S transferase (GST) subunits, rbGST alpha I and rbGST alpha II, have been derived from cDNA sequences. Clones encoding rbGST alpha I were isolated from both hepatic and pulmonary cDNA libraries, whereas clones encoding rbGST alpha II were isolated only from the hepatic library. Immunochemical and peptide sequence data confirmed that rbGST alpha I corresponds to the 27-kDa alpha-class subunit purified from rabbit lung (Serabjit-Singh, C. J., and Bend, J. R. (1988) Arch. Bioch. Biophys. 267, 184-194). Expression of rbGST alpha II in liver but not in lung and expression of rbGST alpha I in both liver and lung was substantiated by Northern and immunochemical analyses. rbGST alpha I and rbGST alpha II are composed of 223 and 221 amino acids, respectively, and are 78% identical in amino acid sequence. Compared to published GST sequences, both proteins are most closely related to the human Ha subunit (greater than 80% identity). On the basis of sequence comparison and Northern and Southern analyses, we conclude that rbGST alpha I and rbGST alpha II are products of different genes that are independently regulated. Further, the regulatory elements of the alpha-class GST genes may be significantly different in the rabbit as compared to the rat, as evidenced by the lack of induction by phenobarbital of rabbit hepatic or pulmonary alpha-class GST subunits, enzymatic activity, or mRNA. This tissue- and species-dependent expression of the predominant class of cytosolic GST implies unique functions for each isozyme and may contribute to the differential susceptibility of tissues and animals to toxicants. PMID- 1918076 TI - Cloning, bacterial expression, purification, and characterization of the cytoplasmic domain of rat LAR, a receptor-like protein tyrosine phosphatase. AB - This report describes the cloning and characterization of rat leukocyte common antigen-related protein (rLAR), a receptor-like protein tyrosine phosphatase (PTPase). The recombinant cytoplasmic PTPase domain was expressed at high levels in bacteria and purified to homogeneity. Kinetic properties of the PTPase were examined along with potential modulators of PTPase activity. Several sulfhydryl directed reagents were effective inhibitors, and a surprising distinction between iodoacetate and iodoacetamide was observed. The latter compound was an extremely poor inhibitor when compared to iodoacetate, suggesting that iodoacetate may interact selectively with a positive charge at or near the active site of the enzyme. Site-directed mutants were made at 4 highly conserved cysteine residues found at positions 1434, 1522, 1723, and 1813 within the protein. The Cys 1522/Ser mutation resulted in a 99% loss of enzymatic activity of the pure protein. This observation is consistent with greater than 99% of the PTPase activity being found in the first domain of the PTPase and demonstrates the critical importance of this cysteine residue in catalysis. The recombinant C1522S mutant phosphatase could also be phosphorylated in vitro by protein kinase C and p43v-abl tyrosine kinase. When pure recombinant PTPase was mixed with 32P-labeled tyrosine substrate and then rapidly denatured, a 32P-labeled enzyme intermediate could be trapped and visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The catalytically inactive C1522S mutant did not form the phosphoenzyme intermediate. PMID- 1918077 TI - Characterization of a chimeric plasminogen activator consisting of a single-chain Fv fragment derived from a fibrin fragment D-dimer-specific antibody and a truncated single-chain urokinase. AB - An Mr 57,000 single-chain chimeric plasminogen activator, K12G0S32, consisting of a variable region fragment (Fv) derived from the fibrin fragment D-dimer-specific monoclonal antibody MA-15C5 and of a 33-kDa (amino acids Ala132 to Leu411) recombinant single-chain urokinase-type plasminogen activator (rscu-PA-33k) was studied. K12G0S32, secreted by infected Spodoptera frugiperda insect cells at a rate of 1.5 micrograms/10(6) cells/48 h, was purified to homogeneity by ion exchange chromatography and gel filtration. It was obtained essentially as a single-chain molecule with a Ka = 5.5 x 10(9) M-1 for immobilized fragment D dimer, similar to that of MA-15C5. The specific activity of both its single-chain and two-chain forms on fibrin plates was 100,000 IU/mg of urokinase-type plasminogen activator (u-PA) equivalent. Activation of plasminogen by two-chain K12G0S32 obeyed Michaelis-Menten kinetics with Km = 2.9 +/- 0.6 microM and a k2 = 3.7 +/- 0.6 s-1 (mean +/- S.D.; n = 3), as compared to Km = 12 microM and k2 = 4.8 s-1 for rtcu-PA-32k (recombinant low Mr two-chain u-PA consisting of amino acids Leu144 to Leu411). Single-chain K12G0S32 induced a dose- and time-dependent lysis of a 125I-fibrin-labeled human plasma clot immersed in citrated human plasma; 50% lysis in 2 h was obtained with 0.70 +/- 0.07 micrograms/ml (mean +/- S.D.; n = 5), as compared with 8.8 +/- 0.1 micrograms/ml for rscu-PA-32k (recombinant low Mr single-chain u-PA consisting of amino acids Leu144 to Leu411) (mean +/- S.D.; n = 3). With two-chain K12G0S32, 50% clot lysis in 2 h required 0.25 +/- 0.03 micrograms/ml (mean +/- S.D.; n = 3), as compared with only 0.62 +/ 0.04 micrograms/ml (mean +/- S.D.; n = 2) for rtcu-PA-32k. These results indicate that low Mr single-chain u-PA can be targeted to a fibrin clot with a single-chain Fv fragment of a fibrin-specific antibody, resulting in a 13-fold increase of the fibrinolytic potency of the single-chain form and a 2.5-fold increase of the potency of the two-chain form. PMID- 1918078 TI - Tandem transcription termination sites in the dnaN gene of Escherichia coli. AB - The dnaN gene of Escherichia coli encodes the beta-subunit of DNA polymerase III and maps between the dnaA and recF genes. We demonstrated previously that dnaN and recF constitute a transcriptional unit under control of the dnaN promoters. However, the recF gene has its own promoter region located in the middle of the dnaN structural gene. In this report, we use S1 mapping of mRNAs, transcriptional and translational fusions to the galK and lacZ genes, and in vitro mutagenesis to identify and characterize three tandem transcription termination sites responsible for transcriptional polarity in the dnaN-recF operon. These sites are located in the dnaN gene, downstream from the recF promoter region. Cumulatively, they terminate about 80% of the untranslated transcripts started at the recF promoters. As expected, they do not reduce transcription coming from the dnaN promoters unless dnaN translation was prematurely disrupted by the presence of a nonsense codon. The particular arrangement of regulatory elements (promoters and terminators) in the dnaN-recF region provides an exceptional in vivo system to confirm the latent termination site model of transcriptional polarity. In addition, our results contribute to the understanding of the complex regulation of the dnaA, dnaN, and recF genes. We propose that these three genes constitute an operon and that the terminators described in this work could be used to reduce expression of the distal genes of the operon under circumstances in which the dnaN translation happens to be slowed down. PMID- 1918079 TI - The 30-kDa mitochondrial proteins induced by hormone stimulation in MA-10 mouse Leydig tumor cells are processed from larger precursors. AB - Acute regulation of steroidogenesis in steroidogenic tissue is controlled by the transfer of cholesterol from the outer to the inner mitochondrial membrane where cleavage to produce pregnenolone occurs. Hormonal stimulation of MA-10 mouse Leydig tumor cells results in a large increase in steroidogenesis and the concomitant appearance of a series of 30-kDa proteins which have been localized to the mitochondria. In the present study we have shown that the appearance of these proteins occurs in a dose-responsive manner with both human chorionic gonadotropin and cyclic AMP analog. We have also shown that while steroidogenesis is inhibited rapidly in response to a cessation of protein synthesis, the 30-kDa mitochondrial proteins remain in the mitochondria, posing a potential dilemma for arguments favoring their role in the acute regulation of steroidogenesis. We report that the 30-kDa mitochondrial proteins arise from two precursor proteins with molecular masses of 37 and 32 kDa which are also found to be associated with the mitochondria. The use of pulse-chase experiments and the inhibitors ortho phenanthroline and carbonyl cyanide m-chlorophenylhydrazone demonstrated the precursor-product relationship between the 37-, 32-, and 30-kDa proteins. We have also demonstrated that, as shown for a number of other mitochondrial proteins, the 30-kDa proteins are transferred to the inner mitochondrial membrane by a process requiring both proteolytic removal of the targeting sequences and an electrical potential across the inner mitochondrial membrane. We propose that during this transfer contact sites form between the two mitochondrial membranes and may offer an ideal situation for the transfer of cholesterol from the outer membrane to the inner membrane by an as yet unknown mechanism. Following transfer, the 30-kDa proteins remain in the inner membrane no longer able to function in the further transfer of cholesterol, and it is the continuing synthesis and processing of more precursor proteins which provides additional substrate for steroidogenesis. PMID- 1918080 TI - Chitinase is required for cell separation during growth of Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae chitinase described by Correa et al. (Correa, J. U., Elango, N., Polacheck, I., and Cabib, E. (1982) J. Biol. Chem. 257, 1392-1397) has been cloned and sequenced. Analysis of the derived amino acid sequence suggests that the protein contains four domains: a signal sequence, a catalytic domain, a serine/threonine-rich region, and a carboxyl-terminal domain with high binding affinity for chitin. Most of the enzyme produced by cells is secreted into the growth medium and is extensively glycosylated with a series of short O linked mannose oligosaccharides ranging in size from Man2 to Man5. Chitinase O mannosylation was further examined in the temperature-sensitive secretion mutants sec18, sec7, and sec6. Oligosaccharides isolated from chitinase accumulating in cells at the nonpermissive temperature revealed Man1 and Man2 associated with the sec18 mutant. sec6 and sec7 accumulated Man2-Man5 with a higher proportion of Man5 relative to the secreted protein. A significant amount of chitinase is also found associated with the cell wall through binding of COOH-terminal domain to chitin. Disruption of the gene for the enzyme leads to a defect in cell separation but does not substantially alter the level of cellular chitin. PMID- 1918081 TI - Purification of the cleavage and polyadenylation factor involved in the 3' processing of messenger RNA precursors. AB - Polyadenylation of messenger RNA precursors requires the nucleotide sequence AAUAAA and two factors: poly(A) polymerase and a specificity factor termed cleavage and polyadenylation factor (CPF). We have purified CPF from calf thymus and from HeLa cells to near homogeneity. Four polypeptides with molecular masses of 160, 100, 73, and 30 kDa cofractionate with CPF activity. Glycerol gradient centrifugation and gel filtration indicate that these four proteins form one large complex with a sedimentation constant of 12 S, a Stokes radius near 100 A, and a native molecular mass near 500 kDa. Purified CPF binds specifically to an RNA that contains the AAUAAA sequence. Mutation of the AAUAAA sequence inhibits CPF binding as well as polyadenylation. Purified CPF contains only trace amounts of RNA and does not react with antibodies against common epitopes of small nuclear ribonucleoprotein particles. Thus, contrary to previous indications, CPF does not appear to be a small nuclear ribonucleoprotein particle. PMID- 1918082 TI - Engineered cysteine mutants of myosin light chain 2. Fluorescent analogues for structural studies. AB - Site-directed mutagenesis has been used to insert cysteine residues at specific locations in the myosin light chain 2 (LC2) sequence. The aim was to modify these cysteines with one or more spectroscopic probes and to reconstitute myosin with labeled light chains for structural studies. Native LC2 has two endogenous cysteine residues at positions 126 and 155; a third sulfhydryl was added by replacing either Pro2, Ser73, or Pro94 with cysteine. By oxidizing the endogenous cysteines to an intramolecular disulfide bond (Katoh, T., and Lowey, S., (1989) J. Cell Biol. 109, 1549), it was expected that the new cysteine could be selectively labeled with a fluorescent probe. This proved more difficult to accomplish than anticipated due to the formation of secondary disulfide bonds between the newly engineered cysteines and the native ones. Nevertheless, the unpaired cysteines were labeled with 5-(iodoacetamido)fluorescein, and singly labeled species were purified by ion-exchange chromatography. Chymotryptic digestion of the light chains, followed by high performance liquid chromatography separation of the peptides, led to the identification of the fluorescein-labeled cysteines. After light chain exchange into myosin, the position of the thiols was mapped by antifluorescyl antibodies in the electron microscope. Rotary-shadowed images showed the antibody bound at the head/rod junction of myosin for all the mutants. These mapping studies, together with the finding that widely separated cysteines can form multiple disulfide bonds, support a model for LC2 as a flexible, globular molecule that resembles other Ca/Mg-binding proteins in tertiary structure. PMID- 1918083 TI - Identification and characterization of xpac protein, the gene product of the human XPAC (xeroderma pigmentosum group A complementing) gene. AB - We have cloned human xeroderma pigmentosum group A complementing (XPAC) cDNA that encodes a "zinc finger" protein with a predicted size of 31 kDa. To detect the xpac protein in cells, we raised antibody against a recombinant human xpac protein. Using this antibody, we identified the xpac protein in the nucleus of cells. In normal human cells, 40- and 38-kDa proteins were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A reduced amount of the smaller protein was detected in XP 39OSSV cells, which show low UV sensitivity, and no xpac proteins were detected in XP 2OSSV cells, which show high UV sensitivity. These levels of xpac proteins in xeroderma pigmentosum cells were determinants of heterogeneity of the DNA repair defect in group A xeroderma pigmentosum. Synthesis of the xpac protein did not increase after UV irradiation. PMID- 1918084 TI - Casein kinase II from Caenorhabditis elegans. Cloning, characterization, and developmental regulation of the gene encoding the beta subunit. AB - Complementary DNAs encoding the beta subunit of casein kinase II (CKII beta) from the nematode Caenorhabditis elegans were cloned and sequenced. The predicted beta subunit polypeptide comprises 234 amino acid residues and has a Mr of 26,452. CKII beta is not homologous with other types of proteins. In synchronously developing C. elegans the abundance of the 1.3-kilobase mRNA for CKII beta varies in parallel with the level of mRNA encoding the catalytic subunit (alpha) of CKII. Thus, the developmental expression of CKII subunits is controlled coordinately and pretranslationally. CKII beta and CKII alpha mRNAs are enriched 5-10-fold in C. elegans embryos relative to their concentrations at several other stages of nematode development. A 3.8-kilobase pair segment of C. elegans DNA that contains the CKII beta gene and an extensive 5'-flanking region was cloned and sequenced. The CKII beta gene is divided into 6 exons by introns ranging from 49 to 533 base pairs in length. The first exon encodes 88 nucleotides of 5' untranslated mRNA. Exon 2 (72 base pairs) contains the initiator Met codon and only 5 additional codons. Exons 3-6 encode 52, 63, 64, and 49 amino acid residues, respectively. The 5' terminus of CKII beta mRNA is modified post transcriptionally by trans-splicing with a leader sequence of 22 nucleotides. The CKII beta gene was mapped to a position on C. elegans chromosome 2 that is in close proximity to the lin-11 gene. PMID- 1918085 TI - Characterization of neutrophil NADPH oxidase factors p47-phox and p67-phox from recombinant baculoviruses. AB - Superoxide production by phagocytic blood cells involves assembly of an active NADPH oxidase complex from components found both in membrane and cytosolic locations in resting cells. We recently cloned cDNAs encoding two cytosolic components (p47-phox and p67-phox) of the oxidase that are deficient in distinct forms of autosomal recessive chronic granulomatous disease. The precise roles of p47-phox and p67-phox were explored further using purified factors produced in large quantities using recombinant baculoviruses to infect cultured Sf9 insect cells. Neither p47-phox nor p67-phox are thought to represent the flavoprotein components of the oxidase, since neither of the purified recombinant factors contained or bound FAD. Recombinant p47-phox and p67-phox are capable of restoring the deficient cytosol from chronic granulomatous disease patient neutrophils to nearly normal levels in a cell-free reconstitution system. Both p47-phox and p67-phox, used together in the absence of neutrophil cytosol, are incapable of supporting cell free production of superoxide, confirming the involvement of other soluble factor(s) in the assembly of an active oxidase in vitro. PMID- 1918087 TI - Constitution of the twin polymerase of DNA polymerase III holoenzyme. AB - It is speculated that DNA polymerases which duplicate chromosomes are dimeric to provide concurrent replication of both leading and lagging strands. DNA polymerase III holoenzyme (holoenzyme), is the 10-subunit replicase of the Escherichia coli chromosome. A complex of the alpha (DNA polymerase) and epsilon (3'-5' exonuclease) subunits of the holoenzyme contains only one of each protein. Presumably, one of the eight other subunit(s) functions to dimerize the alpha epsilon polymerase within the holoenzyme. Based on dimeric subassemblies of the holoenzyme, two subunits have been elected as possible agents of polymerase dimerization, one of which is the tau subunit (McHenry, C. S. (1982) J. Biol. Chem. 257, 2657-2663). Here, we have used pure alpha, epsilon, and tau subunits in binding studies to determine whether tau can dimerize the polymerase. We find tau binds directly to alpha. Whereas alpha is monomeric, tau is a dimer in its native state and thereby serves as an efficient scaffold to dimerize the polymerase. The epsilon subunit does not associate directly with tau but becomes dimerized in the alpha epsilon tau complex by virtue of its interaction with alpha. We have analyzed the dimeric alpha epsilon tau complex by different physical methods to increase the confidence that this complex truly contains a dimeric polymerase. The tau subunit is comprised of the NH2-terminal two-thirds of tau but does not bind to alpha epsilon, identifying the COOH-terminal region of tau as essential to its polymerase dimerization function. The significance of these results with respect to the organization of subunits within the holoenzyme is discussed. PMID- 1918086 TI - Neutral endopeptidase, a major brush border protein of the kidney proximal nephron, is directly targeted to the apical domain when expressed in Madin-Darby canine kidney cells. AB - We have used a retroviral vector containing both the cDNA for rabbit neutral endopeptidase (EC 3.4.24.11; NEP) and the neomycin resistance gene to promote the expression of NEP in a polarized Madin-Darby canine kidney (MDCK) cell line. Cells resistant to G418 (a neomycin synthetic analog) were analyzed with a fluorescence-activated cell sorter to isolate a homogeneous population of cells which stably expressed NEP at their surface. When cells grown in Petri dishes were labeled with an antibody to NEP coupled to colloidal gold and examined under the electron microscope, a strong labeling of microvilli was observed, whereas very few particles were present on the basolateral domain, suggesting that the polarized distribution of this enzyme typical of proximal tubule cells is maintained in this MDCK cell population. To study more accurately the mechanism by which MDCK cells target NEP to the apical surface, cultures were grown to confluence on Costar Transwell chambers and used for pulse-chase experiments with [35S]methionine. Immunoprecipitation of recombinant NEP was then performed by adding an anti-NEP polyclonal antibody to the apical or basolateral surface of intact monolayers and by analyzing immunoprecipitates by gel electrophoresis and fluorography. Our results suggest that NEP is delivered directly to the apical domain and does not transit through the basolateral domain of the plasma membrane. This NEP-expressing MDCK cell line therefore constitutes a new model for investigating the molecular basis of apical membrane targeting in polarized epithelial cells. PMID- 1918088 TI - Alzheimer's amyloid precursor protein produced by recombinant baculovirus expression. Proteolytic processing and protease inhibitory properties. AB - The baculovirus expression system was used to generate recombinant Alzheimer's amyloid precursor (AAP) proteins. Recombinant baculoviruses were constructed, designed to express full-length 695-, 751-, and 770-amino acid forms. Recombinant baculoviruses designed for constitutive secretion were engineered by placing a termination codon between the beta-protein domain and cytoplasmic anchor of the full-length forms. Insect cells infected with each of these baculoviruses produced both secreted and cell-associated AAPs. Full-length constructs produced secreted derivatives which were COOH-terminally cleaved within the beta-protein domain at Gln15 or Lys16, essentially identical to previous reports utilizing mammalian cell systems. Rare secreted forms (less than 5%) appeared to extend to Lys28. Secretion constructs produced these same forms, but in different ratios. Most (approximately 60%) terminated at Gln15 or Lys16, while the remainder apparently extended to Lys28. AAPs containing the Kunitz-type serine protease inhibitory domain (AAP-751 and -770) were shown to be active inhibitors. No differences were observed in the inhibitors activities of these two forms. The similarities in AAP processing by insect and mammalian systems, together with the large amounts of recombinant protein produced by baculovirus expression, make this an attractive system for studies of AAP processing and biochemical properties. PMID- 1918089 TI - Reversal of multidrug resistance by calcium channel blocker SR33557 without photoaffinity labeling of P-glycoprotein. AB - The altered pharmacology of drugs in multidrug-resistant cells (decreased accumulation and retention) appears to be mediated by a high molecular weight integral membrane protein, called P-glycogprotein (P-gp). Agents known to reverse this pleiotropic drug resistance (chemosensitizers) have been shown to interact with P-gp; and as such, the inhibition of photoaffinity labeling by P-gp probes (such as [3H]azidopine) has been proposed as a basis for mass screening of chemosensitizers. In this study, we provide direct evidence that a novel calcium channel blocker (SR33557), which was 4.5 times more potent in sensitizing P388/ADR cells to doxorubicin as compared to verapamil (while inducing a similar increase in uptake and decrease in efflux of [14C]doxorubicin, did not compete for the [3H]azidopine-binding site on P-gp, whereas verapamil did. Moreover, SR33557, which is inherently photoactivable, did not photolabel P-gp, but a 65 kDa protein did appear to be an acceptor; and this binding was displaced by diltiazem and nifedipine, but not by verapamil. Finally, the implication for the participation of a sphingomyelin/sphingosine cycle (as a potential lipid second messenger system) in the chemosensitization of P388/ADR cells was investigated. 30 microM SR33557 induced a 72% inhibition in acid lysosomal sphingomyelinase activity, a 5-fold increase in sphingosine levels, and a 75% inhibition in intracellular protein kinase C activity. Although no direct link is established between these observations and P-gp activity, further studies on a possible sphingosine-mediated regulation of P-gp may yield information on the involvement of this second messenger system in the action of SR33557. PMID- 1918090 TI - Three-dimensional mathematical model analysis of the patellofemoral joint. AB - This paper is concerned with a mathematical model analysis of the patellofemoral joint in the human knee, taking into account the articular surface geometry and mechanical properties of the ligament. It was made by the application of a computer-aided design theory (previously studied) and it was possible to express the articular surface geometries in a mathematical formulation and hence elucidate the joint movement mechanics. This method was then applied to a three dimensional geometrical model of the patellofemoral joint. For the modelling of tendofemoral contact at large angles of knee flexion, the geodestic line theory was adopted. Applying the Newton-Raphson method and the Runge-Kutta Gil method to the model, variables such as patellar attitudes, patellofemoral contact force and tensile force of the patellar ligament for various knee flexion angles were computed. Applying the Hertzian elastic theory, contact stress was also computed. These results showed good agreement with the previously reported experimental results. As an application for the model, some parameter analyses were performed in terms of the contact stress variations and compared with those of the normal knee. The simulation results indicated that both the Q-angle increase and decrease increased contact stress, the patella alta showed undulating variations of stress while the patella infera showed little change of stress, and the tibial tuberositas elevation showed 20-30% reduction of stress. PMID- 1918091 TI - Rotational flexibility of the human knee due to varus/valgus and axial moments in vivo. AB - Knee ligamentous injuries persist in the sport of Alpine skiing. To better understand the load mechanisms which lead to injury, pure varus/valgus and pure axial moments were applied both singly and in combination to the right knees of six human test subjects. The corresponding relative knee rotations in three degrees of freedom were measured. Knee flexion angles for each test subject were 15 and 60 degrees for the individual moments and 60 degrees for the combination moments. For both knee flexion angles the hip flexion angle was 0 degrees. Leg muscles were quiescent and axial force was minimal during all tests. Tables of data include sample statistics for each of four flexibility parameters in each loading direction. Data were analyzed statistically to test for significant differences in flexibility parameters between the test conditions. In flexing the knee from 15 to 60 degrees, the resulting knee rotations under single moments depended upon flexion angle with varus, valgus, and internal rotations increasing significantly. Also, rotations were different depending on load direction; varus rotation was significantly different and greater than valgus rotation at both flexion angles. Also external rotation was significantly different and greater than internal at 15 degrees flexion, but not at 60 degrees flexion. Coupled rotations under single moments were also observed. Applying pure varus/valgus moments resulted in coupled external/internal rotations which were inconsistent and hence not significant. Applying pure axial moments resulted in consistent and hence significant varus/valgus rotations; an external axial moment induced varus rotation and an internal axial moment induced valgus rotation. For combination moments, varus/valgus rotations decreased significantly from those rotations at similar load levels in the single moment studies. Also, a varus moment significantly increased external rotation and a valgus moment significantly decreased internal rotation. These differences indicate significant interaction between corresponding load combinations. These results suggest that load interaction is a potentially important phenomenon in knee injury mechanics. PMID- 1918093 TI - Biomechanical model of the human shoulder joint--II. The shoulder rhythm. AB - A method to investigate the rhythm of the human shoulder, i.e. the interplay between the motion of constituent parts of the shoulder, has been devised and tested. The method is based upon numerical evaluation of low dose roentgenstereophotogrammetric motion pictures of subjects equipped with radiation dense implantations in the bones. Evaluation of the method shows that it may be used in determining motion patterns and that the employed interpolation techniques can be used to simulate motions not actually performed in the laboratory. The shoulder rhythm has been previously poorly investigated and quantified results published pertain to one plane only. Our results on motion patterns correlate with previous investigations. With this method, we show that the absolute position of the bones varies significantly between individuals while the relative displacement of the bones during motion exhibit similarities. In particular the results show that, under normal conditions, the individual rhythm is very stable and insensitive to small hand-loads. PMID- 1918092 TI - The underestimation of Young's modulus in compressive testing of cancellous bone specimens. AB - In order to determine the accuracy of measurements of Young's modulus of cancellous bone by conventional compression testing, two independent strain measurements were made simultaneously during non-destructive uniaxial compression to 0.8% strain of rectangular specimens (n = 18). Strain was measured by an extensometer attached to the compression anvils close to the specimen and by an optical system covering the central half of the specimens. Mean Young's modulus determined by the extensometer technique was 689 MPa, but was 871 MPa when determined by the optical technique (mean difference = 182 MPa, SED = 50 MPa, p less than 0.002). Uneven strain distribution due to lack of support of cut vertical trabeculae at the anvil-specimen interface is believed to be causing the underestimation of Young's modulus measured by the extensometer technique. The influence of friction at the specimen-anvil interface was studied by performing a finite element analysis. It is concluded that Young's modulus of specimens of the chosen geometry on average is underestimated by about 20% by conventional compressing testing. The underestimation seems not to be dependent upon specimen density. PMID- 1918094 TI - A structural model used to evaluate the changing microstructure of maturing rat skin. AB - A microstructurally based model for soft biological tissues was adapted to model the non-linear response of the collagenous network in skin. Quasi-static uniaxial tensile tests were conducted on dorsal skin of rats aged 1-4 months. Specimens were taken longitudinally and transversely (laterally) to the spine and tested at 1.5% s-1. The model showed fiber stiffness to increase laterally during maturation and to be greater laterally than longitudinally. It also indicated the migration of the 'heel' portion of the response curve toward the origin during maturation to be due to less crimping in the fibers. These results were qualitatively supported by microscopical observations. The model was found to be well suited to fit response curves exhibiting a well-defined 'heel' region. For curves exhibiting a more flat, featureless 'heel' region (typical of 1 month longitudinal specimens) the model was not well suited. The results of this study indicate that this simple three-parameter model might be a useful tool in future studies to analyze pathological changes in the collagenous microstructure. PMID- 1918096 TI - A numerical analysis of the backflow between the leaflets of a St Jude Medical cardiac valve prosthesis. AB - Clinically significant, unexplained hemolysis has been reported to occur in St Jude Medical (SJM) cardiac valve prostheses. The leakage phase of backflow is identified as having the most hemolytic potential, when compared with the other phases of the cardiac cycle. A two-dimensional, laminar, constant fluid property finite element analysis (FEA) is used to calculate the peak shear stress obtained in the flow through the narrow slit formed by the closed leaflets of an idealized size 29 mm (tissue annulus diameter) SJM cardiac valve prosthesis, during the leakage phase of backflow. The flow geometry was such that the simple laminar flow theory (SLFT) could be used to model the flow through the region of peak shear stresses with reasonable accuracy. The SLFT predicts that the maximum shear stress depends upon the thickness of the clearance space and the average velocity through that space. These results suggest that the magnitude of the peak shear stress is of the order of 700-1000 Pa for a duration of the order of 0.5-0.4 ms for pressure drops across the valve of 150-300 torr. This suggests that hemolysis is possible for certain unfortunate combinations of clearances and pressure conditions. However, further research is needed before this flow phenomenon can be associated with the reported clinical hemolysis. PMID- 1918095 TI - Optimization of skeletal configuration: studies of scoliosis correction biomechanics. AB - A scheme for optimizing configurations in models of skeletal structures is presented. Use of the scheme is illustrated through determination of biomechanically optimal correction of a right-thoracic scoliosis by passive brace and active muscle forces. The locations and magnitudes of the passive brace forces, and the trunk muscle groups and their corresponding contraction intensity magnitudes that would optimally correct the geometric deformities of the spine were determined. The results suggest that, from a biomechanical viewpoint, both brace and muscle forces are capable of substantial correction of a model thoracic scoliosis. However, comparison of model results with long-term clinical results suggests that even under optimal conditions it is unlikely that scoliosis can be fully corrected by passive brace forces or active muscle contractions. PMID- 1918097 TI - Talocrural and talocalcaneal joint kinematics and kinetics during the stance phase of walking. AB - The purpose of this investigation was to study the kinematics and kinetics of the joints between the leg and calcaneus during the stance phase of walking. The talocrural and talocalcaneal joints were each assumed to act as monocentric single degree of freedom hinge joints. Motion at one joint was defined by the relative rotation of a point on the opposing joint. The results, based upon the gait of three subjects, showed that the hinge joint assumption may be reasonable. A discrepancy in the kinematics was shown between the talocrural joint rotation and its commonly assumed sagittal plane representation, especially during initial flatfoot. This discrepancy is due to the fact that the sagittal plane rotation is created by the combined rotations of the talocrural and talocalcaneal joints. The talocalcaneal joint showed a peak 25-30 Nm supinatory moment at 80% of stance. The talocrural joint moment was qualitatively similar to the commonly measured sagittal plane moment, but the present results show that the sagittal plane moment overpredicted the true moment by 6-22% due to the two-dimensional assumption. PMID- 1918098 TI - Analysis of the interaction between vertebral lateral deviation and axial rotation in scoliosis. AB - There is a lack of clear biomechanical analyses to explain the interaction of the lateral and axial deformity of the spine in idiopathic scoliosis. A finite element model which represented an isolated ligamentous spine with realistic elastic properties and idealized geometry was used to analyse this interaction. Three variations of this model were used to investigate two different hypotheses about the etiology of scoliosis and to define the forces required to produce a scoliosis deformity. The first hypothesis is that coupling within a motion segment produces the interaction between lateral deviation and axial rotation. The second hypothesis is that posterior tethering by soft tissues in the growing spine produces the observed interaction. Modeling of both hypotheses failed to produce the clinically observed pattern of interaction. Therefore, to find which biomechanical forces were required to produce an idealized scoliosis, prescribed displacements were applied to the model. Production of a double curve scoliosis of 10 degrees Cobb angles required lateral forces on the order of 20 N acting 40 mm anterior to the vertebral body centers. There do not appear to be any anatomic structures capable of producing such forces. Therefore, it seems unlikely that scoliosis deformity can be explained in terms of forces acting on the spine, and understanding of its origins may come from examination of other mechanisms such as asymmetric thoracic growth, or asymmetric vertebral development. PMID- 1918099 TI - Quantitation of articular surface topography and cartilage thickness in knee joints using stereophotogrammetry. AB - An analytical stereophotogrammetry (SPG) technique has been developed based upon some of the pioneering work of Selvik [Ph.D. thesis, University of Lund, Sweden (1974)] and Huiskes and coworkers [J. Biomechanics 18, 559-570 (1985)], and represents a fundamental step in the construction of biomechanical models of diarthrodial joints. Using this technique, the precise three-dimensional topography of the cartilage surfaces of various diarthrodial joints has been obtained. The system presented in this paper delivers an accuracy of 90 microns in the least favorable conditions with 95% coverage using the same calibration method as Huiskes et al. (1985). In addition, a method has been developed, using SPG, to quantitatively map the cartilage thickness over the entire articular surface of a joint with a precision of 134 microns (95% coverage). In the present study, our SPG system has been used to quantify the topography, including surface area, of the articular surfaces of the patella, distal femur, tibial plateau, and menisci of the human knee. Furthermore, examples of cartilage thickness maps and corresponding thickness data including coefficient of variation, minimum, maximum, and mean cartilage thickness are also provided for the cartilage surfaces of the knee. These maps illustrate significant variations over the joint surfaces which are important in the determination of the stresses and strains within the cartilage during diarthrodial joint function. In addition, these cartilage surface topographies and thickness data are essential for the development of anatomically accurate finite element models of diarthrodial joints.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918100 TI - A biomechanical revolution. PMID- 1918101 TI - The stabilization of fibrillar collagen matrices with 3,4-dihydroxyphenylalanine. AB - Pepsin-treated type I collagen fibrils were reconstituted by warming to 37 degrees C in the presence of DOPA at a concentration of 1 x 10(-3)M. Following a 1-1.5-h lag period the "gels" became progressively stabilized as indicated by an inability to disperse these at 0 degrees C. Following 24 h of incubation at 37 degrees C, the DOPA-collagen gels were insoluble in dilute acetic acid even under denaturing conditions. The effect on both gel stability and solubility was concentration-dependent and was maximum at 1 x 10(-3)M. Gel solubility changes were significant, with the greatest change occurring between concentrations of 3.1 x 10(-5)M and 1.65 x 10(-5)M. DOPA exposure did not alter the fibrillar banding pattern seen at the electron microscopic level. Collagen felts prepared by lyophilization of DOPA-collagen gels demonstrated an increase in shrinkage temperature which after 24 h exceeded that of rat tail tendon. Preformed collagen felts incubated for 24 h in the presence of 1 mM DOPA also had a greatly increased shrinkage temperature. Pepsin-treated collagen control felts were altered with respect to control felts in a time dependent manner. The wet tensile strength increased to four times that of control after 3 days of incubation at 37 degrees C. Matrix extensibility initially increased to 1.5 times that of control felts after 4 days of incubation at 37 degrees C, but decreased to below control values following 6 additional days of incubation. These properties suggest that DOPA may be useful as a stabilizing agent of collagen biomedical prostheses. PMID- 1918102 TI - Low wear rate of UHMWPE against zirconia ceramic (Y-PSZ) in comparison to alumina ceramic and SUS 316L alloy. AB - Partially stabilized zirconia ceramic is being recognized among ceramics for its high strength and toughness. With this ceramic, is possible to manufacture a 22 mm-size femoral head for low friction arthroplasty of the hip joint in association with an ultra-high-molecular-weight polyethylene socket. Wear resistant properties of zirconia ceramic were screened on two principally different wear devices. Sterile calf bovine serum, physiological saline, and distilled water were chosen as the lubricant fluid media. Depending on the lubricant medium, the wear factor of polyethylene against zirconia ceramic counterfaces was 40 to 60% less than that against alumina ceramic counterfaces, and 5 to 10 times lower than with the SUS316L metal counterfaces. Polyethylene wear against metal was more susceptible in saline in which it had 2 to 3 times higher wear rate than with serum. On the other hand, different fluid media had little effect on polyethylene wear against ceramic counterfaces. In each set of tests, the wear factor obtained on an unidirectional wear device showed 10 to 15 times higher values, in comparison to the wear factor estimated on a reciprocating wear device. PMID- 1918103 TI - An in vivo model to study the pathobiology of infectious biofilms on biomaterial surfaces. AB - This study examines the morphology, ultrastructure, and microbiology of the intact biofilm developing on an implant surface. Silastic subdermal implant material was colonized with P. aeruginosa and surgically inserted into the peritoneal cavity of adult rabbits. After 4, 8, 28, and 42 days implants were recovered and the intact biofilms examined. P. aeruginosa colonized the implant throughout the entire experimental time. Microcolonies of glycocalyx-coated bacteria were observed within the biofilm. However, the bulk of the biofilm was host-generated and typically contained phagocytes trapped within a thick mesh of fibrin. Polymorphonuclear neutrophils were the predominant cell type. Isolated erythrocytes, macrophages, and fibroblasts were also observed. By day 28, the biofilm was enclosed in a fibrous capsule of vascularized connective tissue. The low numbers of neutrophils seen in biofilms from sterile Silastic sheets implanted into control animals suggested that neutrophilia may represent a specific cellular response to the bacterial colonization. The results indicate that the cell-mediated immune response provides for most of the biofilm mass on colonized implant surfaces. Inactivated phagocytes trapped in fibrin may "wall off" the embedded bacterial microcolonies and thus shield them from live phagocytic leucocytes. Such a mechanism may play an important role in the pathogenesis of prosthetic device infections. PMID- 1918104 TI - Platelet consumption by polyvinyl alcohol coated tubing in canines. AB - Polyvinyl alcohol (PVA)-coated polyethylene tubing, with or without immobilized heparin, caused severe thrombocytopenia and enhanced the production of new platelets when inserted in a chronic arteriovenous shunt in canines. A similar length of uncoated polyethylene tubing neither lead to thrombocytopenia nor significantly enhanced platelet regeneration, relative to the shunt only without a test section. Platelet regeneration was monitored by the malondialdehyde assay, which was assumed to make a distinction between "new" and "old" platelets. This distinction was combined with the platelet count values to enable calculation of the cumulative consumption curve and the initial fractional consumption rate in the presence of a non constant platelet count. The resulting initial fractional consumption rates were: 34%/day for PVA, 20.5%/day for polyethylene, and 18%/day for the shunt only blank. PMID- 1918105 TI - Influence of surface characteristics on bone integration of titanium implants. A histomorphometric study in miniature pigs. AB - The purpose of the present study was to evaluate the influence of different surface characteristics on bone integration of titanium implants. Hollow-cylinder implants with six different surfaces were placed in the metaphyses of the tibia and femur in six miniature pigs. After 3 and 6 weeks, the implants with surrounding bone were removed and analyzed in undecalcified transverse sections. The histologic examination revealed direct bone-implant contact for all implants. However, the morphometric analyses demonstrated significant differences in the percentage of bone-implant contact, when measured in cancellous bone. Electropolished as well as the sandblasted and acid pickled (medium grit; HF/HNO3) implant surfaces had the lowest percentage of bone contact with mean values ranging between 20 and 25%. Sandblasted implants with a large grit and titanium plasma-sprayed implants demonstrated 30-40% mean bone contact. The highest extent of bone-implant interface was observed in sandblasted and acid attacked surfaces (large grit; HCl/H2SO4) with mean values of 50-60%, and hydroxylapatite (HA)-coated implants with 60-70%. However, the HA coating consistently revealed signs of resorption. It can be concluded that the extent of bone-implant interface is positively correlated with an increasing roughness of the implant surface. PMID- 1918106 TI - Calcium phosphate formation at the surface of bioactive glass in vitro. AB - The calcium phosphate formation at the surface of bioactive glass was studied in vitro. Glass rods and grains were immersed in different aqueous solutions and studied by means of scanning electron microscopy and energy dispersive x-ray analysis. Surface morphological changes and weight loss of corroded grains were monitored. In-depth compositional profiles were determined for rods immersed in the different solutions. The solutions used were tris-buffer (tris hydroxymethylaminomethane + HCl), tris-buffer prepared using citric acid (tris hydroxymethylaminomethane + C6H8O7.H2O), and a simulated body fluid, SBF, containing inorganic ions close in concentration to those in human blood plasma. It was found that the calcium phosphate formation at the surface of bioactive glass in vitro proceeds in two stages. When immersing the glass in tris or in SBF a Ca,P-rich surface layer forms. This accumulation takes place within the silica structure. Later, apatite crystals forming spherulites appear on the surface. The Ca/P-ratio of initially formed calcium phosphate was found to be about unity. It is proposed that this is due to bonding of phosphate to a silica gel. The surface is stabilized, i.e., leaching is retarded, by the rapid Ca,P-accumulation within the silica structure before apatite crystals are observed on the surface. It is proposed that the initially formed calcium phosphate is initiated within the silica gel. The crystallizing surface provides nucleation sites for extensive apatite formation on the glass surface. In the presence of citrate no Ca,P accumulation occur at the glass surface, but soluble Ca-citrate complexes form. By comparing the weight loss during corrosion in tris with that in the calcium and phosphate containing SBF, it is possible to establish whether the glass can induce apatite formation at its surface or not. PMID- 1918107 TI - Charge-injection densities of iridium and iridium-ion-implanted Ti-6A1-4V with relevancy to neural stimulation. PMID- 1918108 TI - Initiation of mineralization in bioprosthetic heart valves: studies of alkaline phosphatase activity and its inhibition by AlCl3 or FeCl3 preincubations. AB - The principal cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde-pretreated porcine aortic valves is calcification. Other prostheses composed of tissue-derived and polymeric biomaterials also are complicated by deposition of mineral. We have previously demonstrated that: (a) Failure due to calcification of clinical bioprosthetic valves can be simulated by either a large animal circulatory model or subdermal implants in rodents. (b) Calcification of bioprosthetic tissue has complex host, implant, and mechanical determinants. (c) The initial calcification event in the rat subdermal model is the mineral deposition in devitalized cells intrinsic to the bioprosthetic tissue within 48 to 72 h, followed later by collagen mineralization. (d) Initiation of bioprosthetic tissue mineralization, like that of physiological bone formation, has "matrix vesicles" as early nucleation sites. (e) Alkaline phosphatase (AP), an enzyme also associated with matrix vesicles involved in bone mineral nucleation, is present in both fresh and fixed bioprosthetic tissue at sites of initial mineralization. (f) Certain inhibitors of bioprosthetic tissue calcification (e.g., Al3+, Fe3+) are localized to the sites at which alkaline phosphatase is present. On the basis of these results, we hypothesize that alkaline phosphatase is a key element in the pathogenesis of mineralization of bioprosthetic tissue. In the present studies, we focused on the relationship of AP to early events in calcification, and the inhibition of both calcification and AP activity by FeCl3 and AlCl3 preincubations. Subdermal implants of glutaraldehyde pretreated bovine pericardium (GPBP) were done in 3-week-old rats. AP was characterized by enzymatic hydrolysis of paranitrophenyl phosphate (pnpp), and by histochemical studies. Calcification was evaluated chemically (by atomic adsorption spectroscopy) and morphologically (by light microscopy). The results of these studies are as follows: (a) Extractable AP activity is present in fresh but not glutaraldehyde-pretreated bovine pericardial tissue. However, histochemical studies reveal active AP within the intrinsic devitalized cells of GPBP, despite extended glutaraldehyde incubation. (b) Extrinsic AP is rapidly adsorbed following implantation, with peak activity at 72 h (424 +/- 67.2 nm pnpp/mg protein/min enzyme activity [units]), but markedly lesser amounts at 21 days (96.8 +/- 3.9 units). (c) Simultaneously to the AP activity maximum, bulk calcification is initiated, with GPBP calcium levels rising from 1.2 +/- 0.1 (unimplanted) to 2.4 +/- 0.2 micrograms/mg at 72 h, to 55.6 +/- 3.1 micrograms/mg at 21 days, despite a marked decline in AP activity at this later time.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1918109 TI - Prevention of bacterial colonization on polyurethane in vitro by incorporated antibacterial agent. AB - The presence of implanted biomaterials increases host susceptibility to infections. Once established, biomaterial-mediated infections are resistant to treatment and persist until the device is removed. The objective of this work was to study the prevention of bacterial-biofilm formation on polymeric implant (polyurethane) by controlled release of incorporated antibacterial agents (parabens). By embedding parabens in PU by the solvent-cast method, matrices with amorphous dispersions (or solid solutions) were obtained. Release rate modulation was achieved by using different MW parabens and by a rate-limiting membrane. Preliminary in vitro antibacterial studies of both methyl and propyl paraben matrices exhibited significant inhibition of Staphylococcus epidermidis biofilm formation. Propyl paraben matrices (15 and 20% w/w drug load) decreased the number of colony-forming units on PU surface to 2 x 10(4)/mL, in comparison to 6 x 10(5) on control polymers. This significant reduction was obtained without any effect on the number of viable bacteria in the suspension culture. This type of delivery system provides regional prophylactic activity by creating a high local concentration of antibacterial agent. PMID- 1918110 TI - A sense of history. PMID- 1918111 TI - Osteomyelitis in patients who have sickle-cell disease. Diagnosis and management. AB - Fifteen patients who had sickle-cell disease and osteomyelitis (affecting thirty bones) were treated with operative decompression and parenteral administration of antibiotics between 1973 and 1988. Organisms were isolated on culture of specimens of bone from all fifteen patients. Parenteral antibiotic therapy was continued for a minimum of six weeks after operative decompression. The osteomyelitis resolved in twenty-nine (97 per cent) of the thirty affected bones after follow-up ranging from two to fifteen years. With their compromised immune status and poor circulation of blood in bone, patients who have sickle-cell disease and osteomyelitis are prone to have complications. In our series, the complications included an adhesive pericapsulitis of the shoulder in two patients, avascular necrosis of the humeral head in one, and a pathological fracture of the femur in one. In four of the fifteen patients, chronic osteomyelitis persisted, but in three of the four, the infections of bone healed six to fourteen months after the initial operative decompression. Staphylococcus aureus was isolated on culture of specimens of bone from eight to the fifteen patients; Salmonella, from six; and Proteus mirabilis, from one. Although Salmonella has been cited as the principal causative organism of osteomyelitis in patients who have sickle-cell disease, in our experience Staphylococcus aureus was the most common infecting organism. Therefore, Salmonella may not be the most common cause of osteomyelitis associated with sickle-cell disease in all countries or in all areas of a particular country. PMID- 1918112 TI - The potential for regeneration of articular cartilage in defects created by chondral shaving and subchondral abrasion. An experimental investigation in rabbits. AB - Animal models for chondral shaving and subchondral abrasion were created to resolve the controversy about the nature of the repair tissue after these procedures and to determine the effect of continuous passive motion on the quality of the repair tissue. Chondral shaving was performed on the patella in forty adolescent rabbits, and subchondral abrasion was performed on the patella in another forty rabbits. In both procedures, a three-millimeter-diameter defect was created. After the operation, twenty animals from each group were allowed intermittent active motion; the remainder were treated by continuous passive motion for two weeks, followed by intermittent active motion. Half of the animals from each group were killed at four weeks and the other half, at twelve weeks. There was no evidence of repair tissue in the defects at either four or twelve weeks after chondral shaving, regardless of the postoperative treatment. The remaining underlying cartilage, however, had degenerated. After abrasion of subchondral bone, the defects in animals that were treated with only intermittent active motion healed at twelve weeks, although the quality of the repair tissue varied. All ten of the animals that were treated with continuous passive motion, however, had mature, hyaline-like cartilage as the predominant repair tissue at twelve weeks, compared with six of the ten animals that were treated with intermittent active motion (p less than 0.05). We concluded that, in this model, partial-thickness defects created by chondral shaving do not heal; rather, the remaining underlying cartilage degenerates. Full-thickness defects created by subchondral abrasion can heal by regeneration of hyaline-like cartilage. Such healing is enhanced by continuous passive motion for two weeks postoperatively. PMID- 1918113 TI - The timing of flap coverage, bone-grafting, and intramedullary nailing in patients who have a fracture of the tibial shaft with extensive soft-tissue injury. AB - The cases of forty-three patients who had a Type-IIIB open fracture of the tibial shaft were reviewed to determine the effect of treatment of the soft-tissue injury on the rate of major complications. An infection developed in two of the eleven patients who had had early muscle-flap coverage compared with ten of the nineteen who had been managed by open care of the wound and nine of the thirteen who had had later flap coverage. Patients who had had bone-grafting after complete re-epithelialization of the wound, regardless of the method of closure, had a lower rate of early infection (none of sixteen compared with four of fifteen) and an earlier average time to union (fifty-four compared with sixty three weeks) than those in whom the wound was not completely closed or was draining at the time of bone-grafting. Delayed intramedullary nailing with reaming was associated with a high rate of infection (nine of nineteen patients), regardless of the condition of the soft tissue at the time of nailing. In our opinion, adequate debridement and early assessment of the soft-tissue defect are necessary so that appropriate soft-tissue coverage can be provided within the first one to two weeks. When the soft-tissue portion of the injury is addressed promptly and definitively and then allowed to heal completely, secondary osseous reconstruction may proceed with fewer complications. PMID- 1918114 TI - A comparison of the effects of skin coverage and muscle flap coverage on the early strength of union at the site of osteotomy after devascularization of a segment of canine tibia. AB - A study was done to compare the effects of coverage with skin and those of coverage with a muscle flap on the early return of strength at the site of an osteotomy after interposition of a devascularized segmental autogenous graft, two centimeters long, from a canine tibia. The bone was fixed with a plate. Thirty two animals were randomized into two groups, one of which was treated with skin coverage and the other of which was treated with muscle flap coverage. Half of the animals from each group were killed at eight weeks and half, at twelve weeks postoperatively. The tibiae were tested to failure in four-point bending. Failure occurred primarily through the site of the distal osteotomy. Maximum bending load (p = 0.0002) and energy absorbed to failure (p less than 0.02) increased significantly between eight and twelve weeks postoperatively in the group in which a muscle flap had been used for coverage. Bending stiffness was significantly greater at eight weeks in the group in which a muscle flap had been used for coverage than in the group in which skin had been used (p less than 0.03). Maximum bending load was also significantly increased at twelve weeks in the group in which a muscle flap had been used compared with the group in which skin had been used (p less than 0.05). PMID- 1918115 TI - Ingrowth of bone in failed fixation of porous-coated femoral components. AB - In five straight-stemmed, proximally porous-coated femoral components that were retrieved at revision arthroplasty from patients who had radiographic and clinical evidence of loosening, there was growth of bone into the porous coating. The components had been inserted during a primary arthroplasty in one woman and four men. The patients ranged in age from thirty-seven to sixty-seven years. Three patients were heavy, and all five were active. All patients had had an excellent early result from the initial arthroplasty; at the one-year follow-up, the mean Harris hip score had been 91 points. Pain in the hip developed in all of the patients, between one and three years after the index procedure. Initial radiographs had revealed excellent position and fixation of the prosthetic components, but the components then subsided between one and three and one-half years after the index procedure. All of the femoral components were found to be grossly loose at the revision operation. Nevertheless, all of the prosthetic components demonstrated growth of bone into 4 to 44 per cent (mean, 24 per cent) of the pore spaces available for ingrowth. Woven bone and fracture callus were found in the curettings from the proximal part of the femur. The findings in these five patients suggest that late failure of uncemented porous-surfaced femoral components can occur despite the presence of extensive ingrowth of bone. These failures may be the result of fatigue fractures of the trabeculae of the osseous ingrowth into the porous surfaces. Caution is warranted in the liberal use of these prosthetic components in heavy, active patients. PMID- 1918116 TI - Shelf arthroplasty in patients who have Legg-Calve-Perthes disease. A study of long-term results. AB - We reviewed the long-term functional and roentgenographic outcomes of severe Legg Calve-Perthes disease in two similar groups of patients, one of which was managed with a shelf arthroplasty and the other, by a variety of non-operative means. Twenty hips in nineteen patients were treated with traction and, when necessary, adductor tenotomy to attempt reduction of the subluxation; this was followed by a shelf arthroplasty to increase the arc of the acetabulum and result in coverage of the femoral head. The average duration of follow-up was nineteen years (range, two to forty-seven years). The initial center-edge angle and the anteroposterior Mose sphericity measurement were significantly improved at the most recent follow up (p greater than or equal to 0.05), and the average Iowa hip score was 91 points. Hinge abduction, which was producing incongruity, was eliminated in eleven of fourteen hips after the operation. The outcomes for the second group, consisting of eighteen hips in seventeen patients who were managed non operatively, were also reviewed, at an average duration of follow-up of twenty eight years (range, seven to forty-five years). No significant improvement in the center-edge angle or the anteroposterior Mose sphericity measurement was observed at the most recent follow-up, and the average Iowa hip score was 81 points. There was no significant difference in the range of motion of the hip between the groups. We believe that shelf arthroplasty is a favorable option in the treatment of Legg-Calve-Perthes disease when additional bone is needed at the lateral aspect of the acetabulum to cover the extruded portion of the femoral head, to prevent additional incongruity and thereby delay the early onset of degenerative changes. PMID- 1918117 TI - Long-term results of total hip arthroplasty in congenital dislocation and dysplasia of the hip. A follow-up note. AB - Twenty-three of twenty-nine hips that were previously reported on were studied at an average of fourteen years (range, eight to 16.5 years) after total hip arthroplasty with cement. The original arthroplasties had been performed between November 1971 and January 1976. In all hips, there was dislocation or severe dysplasia. In six hips, superolateral bone grafts were used to increase acetabular coverage. At the latest follow-up examination, seven hips were rated excellent; nine, good; and one, fair. There were six failures (26 per cent) that were revised: four hips (17 per cent) had a fractured Trapezoidal-28 stem, one had loose femoral and acetabular components, and one had loosening of only the acetabular component. Radiographic analysis of the remaining hips revealed that one had progressive acetabular radiolucencies. This patient had an excellent clinical result. Two-thirds of the failures were due to a fractured stem. PMID- 1918118 TI - Removal of a well fixed acetabular component. A brief technical note of a new method. PMID- 1918119 TI - Structural bone-grafting for early atraumatic avascular necrosis of the femoral head. AB - Between 1970 and 1987, nineteen patients, thirty-one to fifty-five years old, had twenty core-decompression procedures with corticocancellous bone-grafting for Stage-I or II atraumatic avascular necrosis of the femoral head. A tibial autogenous graft was used in three hips; a fibular autogenous graft, in seven hips; and a fibular allograft, in ten hips. Treatment was considered to have failed when there was clinical or roentgenographic evidence of progression of the necrosis. Eighteen patients who had a minimum follow-up of two years (average, eight years; range, two to nineteen years) were asymptomatic, with no evidence of progression of the necrosis or collapse of the affected segment. In two hips, the necrotic segment of the femoral head collapsed within one year after the operation, and a replacement arthroplasty was carried out. PMID- 1918121 TI - The effect of simulated fracture-angulations of the tibia on cartilage pressures in the knee joint. AB - The effects of angular deformities of the tibia on the contact areas and pressures on cartilage in the knee were measured with use of pressure-sensitive film. Six cadaver knees were mounted in a test-frame, such that the offset and tilt of the knee relative to the load-axis simulated that due to angular deformities of the tibia of 5, 10, 15, or 20 degrees of varus or valgus at the levels of the proximal, middle, and distal thirds. Angulation had little effect on the contact area. The change in pressure was least for fractures of the distal third and greatest for fractures of the proximal third. For example, a 20-degree angulation of the distal third increased the maximum contact pressure by an average of 26 per cent in the compartment toward the load-axis and reduced it by 32 per cent in the opposite compartment. With an angulation of 20 degrees at the level of the proximal third of the tibia, the increase in pressure averaged 106 per cent and the decrease averaged 89 per cent. The changes in pressure with fractures at the middle third were between these extremes. PMID- 1918122 TI - Radial wedge osteotomy for Kienbock disease. AB - A radial wedge osteotomy, with reduction of the inclination angle of the distal part of the radius, was performed in twenty-seven patients who had Kienbock disease. After two to five years of follow-up, all of the patients were free of pain or had only mild pain in the wrist with strenuous activity. Flexion extension of the wrist improved by more than 10 degrees in about half of the patients, and in most of the patients the grip strength increased by five kilograms or more. All but two of the postoperative results were satisfactory, as evaluated by the criteria of Lichtman et al. The osteotomy was effective even in patients who had zero or positive ulnar variance. PMID- 1918120 TI - Rotationplasty for limb salvage in the treatment of malignant tumors at the knee. A follow-up study of seventy patients. AB - Seventy patients who had a rotationplasty for treatment of a malignant tumor in the region of the knee (the femur or the tibia) between 1974 and 1987 were followed for two to thirteen years (mean duration of follow-up, four years). Forty-seven patients had a stage-IIB osteosarcoma; the remaining twenty-three patients had a malignant fibrous histiocytoma, a chondrosarcoma, a Ewing sarcoma, or a giant-cell tumor. The most severe postoperative complication was occlusion of the reanastomosed vessels (seven patients), leading to amputation proximal to the knee in three patients. Other complications were problems with wound-healing (eight patients), transient nerve palsy (five patients), irreversible nerve palsy (two patients), pseudarthrosis (four patients), and rotational malalignment (one patient). Late complications included eight fractures, two infections, two delayed unions, and one lymphatic fistula. More than half of the patients were free of complications related to the operative procedure. Forty-four of the patients who had a stage-IIB osteosarcoma could be followed, and their data were analyzed for survival statistics. These patients had a 58 percent rate of disease free survival and a 70 per cent rate of over-all survival. One patient had a local recurrence five years after the operation. PMID- 1918123 TI - The effect of metallic implants on magnetic resonance imaging. A brief note. PMID- 1918124 TI - Lateral compression injury of the pelvis. A case report. PMID- 1918125 TI - Spontaneous dislocation of a vertebra in a patient who had neurofibromatosis. Report of a case with dural ectasia. PMID- 1918126 TI - Synovial chondromatosis with secondary subluxation of the hip. A case report. PMID- 1918127 TI - The formation of the orthopaedic physician and surgeon. PMID- 1918128 TI - The making of a pediatric orthopaedist--the winds of change. PMID- 1918129 TI - Transforming growth factor-beta and remodeling of bone. PMID- 1918131 TI - Computerized tomography scanning of acute intra-articular fractures of the calcaneus. A new classification system. PMID- 1918130 TI - Evaluation of an electrogoniometric instrument for measurement of laxity of the knee. PMID- 1918132 TI - A human centrosomal protein is immunologically related to basal body-associated proteins from lower eucaryotes and is involved in the nucleation of microtubules. AB - Isolation of centrosomes from human cells has revealed a proteic pattern which is both complex and specific. As the most prominent structural element of centrosomes in animal cells, the centriole which is present as two copies, is a highly conserved structure, we have attempted to identify centrosomal proteins on the basis of immunocross-reaction with proteins identified in basal bodies from lower eucaryotes. We report that two antibodies, one raised against the Ca(+) binding protein centrin (Salisbury, J. L., A. T. Baron, B. Surek, and M. Melkonian. 1984. J. Cell Biol. 99:962-970) and the other directed against a 230 kD protein isolated from the infraciliary cytoskeletal lattice of the protozoan Polyplastron m., decorate the centrosome of human cultured cells, and identify one of the major centrosomal components revealed as a doublet of 62/64 kD. Moreover the nucleation reaction of microtubules, which can be efficiently produced on isolated centrosomes, is blocked by the antibodies, a result which strongly implicates the 62/64-kD protein in this centrosomal activity. We also show that the 62/64-kD protein remains insoluble in conditions (0.5 M KI or 8 M urea) which are capable of extracting most of the centrosomal proteins. Immunocytochemical localization by EM of isolated centrosomes revealed the association of this 62/64-kD doublet with the intercentriolar link and the pericentriolar lattice. Our results suggest that conservation of structure in the centrosome from divergent organisms could be matched by conservation of proteins and activity, evidence for the maintenance of a specific function, which could involve Ca2+, associated with the microtubule organizing centers. PMID- 1918133 TI - Colocalization of synaptophysin with transferrin receptors: implications for synaptic vesicle biogenesis. AB - We have reported previously that the synaptic vesicle (SV) protein synaptophysin, when expressed in fibroblastic CHO cells, accumulates in a population of recycling microvesicles. Based on preliminary immunofluorescence observations, we had suggested that synaptophysin is targeted to the preexisting population of microvesicles that recycle transferrin (Johnston, P. A., P. L. Cameron, H. Stukenbrok, R. Jahn, P. De Camilli, and T. C. Sudhof. 1989. EMBO (Eur. Mol. Biol. Organ.) J. 8:2863-2872). In contrast to our results, another group reported that expression of synaptophysin in cells which normally do not express SV proteins results in the generation of a novel population of microvesicles (Leube, R. E., B. Wiedenmann, and W. W. Franke. 1989. Cell. 59:433-446). We report here a series of morphological and biochemical studies conclusively demonstrating that synaptophysin and transferrin receptors are indeed colocalized on the same vesicles in transfected CHO cells. These observations prompted us to investigate whether an overlap between the distribution of the two proteins also occurs in endocrine cell lines that endogenously express synaptophysin and other SV proteins. We have found that endocrine cell lines contain two pools of membranes positive for synaptophysin and other SV proteins. One of the two pools also contains transferrin receptors and migrates faster during velocity centrifugation. The other pool is devoid of transferrin receptors and corresponds to vesicles with the same sedimentation characteristics as SVs. These findings suggest that in transfected CHO cells and in endocrine cell lines, synaptophysin follows the same endocytic pathway as transferrin receptors but that in endocrine cells, at some point along this pathway, synaptophysin is sorted away from the recycling receptors into a specialized vesicle population. Finally, using immunofluorescent analyses, we found an overlap between the distribution of synaptophysin and transferrin receptors in the dendrites of hippocampal neurons in primary cultures before synapse formation. Axons were enriched in synaptophysin immunoreactivity but did not contain detectable levels of transferrin receptor immunoreactivity. These results suggest that SVs may have evolved from, as well as coexist with, a constitutively recycling vesicular organelle found in all cells. PMID- 1918134 TI - Extracellular synaptic factors induce clustering of acetylcholine receptors stably expressed in fibroblasts. AB - The clustering of nicotinic acetylcholine receptors (AChRs) is one of the first events observed during formation of the neuromuscular junction. To determine the mechanism involved in AChR clustering, we established a nonmuscle cell line (mouse fibroblast L cells) that stably expresses just one muscle-specific gene product, the AChR. We have shown that when Torpedo californica AChRs are expressed in fibroblasts, their immunological, biochemical, and electrophysiological properties all indicate that fully functional cell surface AChRs are produced. In the present study, the cell surface distribution and stability of Torpedo AChRs expressed in fibroblasts (AChR-fibroblasts) were analyzed and shown to be similar to nonclustered AChRs expressed in muscle cells. AChR-fibroblasts incubated with antibodies directed against the AChR induced the formation of small AChR microclusters (less than 0.5 micron 2) and caused an increase in the internalization rate and degradation of surface AChRs (antigenic modulation) in a manner similar to that observed in muscle cells. Two disparate sources of AChR clustering factors, extracellular matrix isolated from Torpedo electric organ and conditioned media from a rodent neuroblastoma-glioma hybrid cell line, each induced large (1-3 microns 2), stable AChR clusters with no change in the level of surface AChR expression. By exploiting the temperature sensitive nature of Torpedo AChR assembly, we were able to demonstrate that factor-induced clusters were produced by mobilization of preexisting surface AChRs, not by directed insertion of newly synthesized AChRs. AChR clusters were never observed in the absence of extracellular synaptic factors. Our results suggest that these factors can interact directly with the AChR. PMID- 1918135 TI - Coordinate developmental regulation of purine catabolic enzyme expression in gastrointestinal and postimplantation reproductive tracts. AB - Using histochemical detection, we have visualized in situ the complete metabolic pathway for the degradation of purine nucleotides. From the tongue to the ileum, diverse epithelial cell types lining the lumen of the mouse gastrointestinal (GI) tract strongly coexpress each of the five key purine catabolic enzymes. Dramatic increases in the expression of each enzyme occurred during postnatal maturation of the GI tract. Using in situ hybridization, an intense accumulation of adenosine deaminase (ADA) mRNA was detected only within GI epithelial cells undergoing postmitotic differentiation. In a similar manner, at the developing maternal-fetal interface, high level expression of the purine catabolic pathway also occurred in a unique subset of maternal decidual cells previously known to express high levels of alkaline phosphatase and ADA. This induction occurred almost immediately after implantation in the periembryonic maternal decidual cells, shortly thereafter in antimesometrial decidual cells, and later in cells of the placental decidua basalis: all of which contain cell types thought to be undergoing programmed cell death. The expression of the pathway at the site of embryo implantation appears to be critical because its pharmacologic inhibition during pregnancy has been found to be embryolethal or teratogenic. Purine destruction at these nutritional interfaces (placenta and gastrointestinal tract) seem to override any potential economy of purine salvage, and may represent biochemical adaptation to nucleic acid breakdown occurring in the context of dietary digestion or extensive programmed cell death. PMID- 1918136 TI - Metastatic behavior of human melanoma cell lines in nude mice correlates with urokinase-type plasminogen activator, its type-1 inhibitor, and urokinase mediated matrix degradation. AB - Five out of six human melanoma cell lines tested were able to degrade in vitro a smooth muscle cell extracellular matrix in a plasmin-dependent way. In three of these five cell lines, this process was mediated by tissue-type plasminogen activator (t-PA) and in the other two cell lines by urokinase-type plasminogen activator (u-PA). All melanoma cell lines produced t-PA mRNA and protein, whereas only the two cell lines showing u-PA-mediated matrix degradation produced u-PA mRNA and protein. These latter cell lines also produced plasminogen activator inhibitor type-1 (PAI-1) and type-2 (PAI-2) mRNA and protein. u-PA receptor (u-PA R) mRNA and binding of radiolabeled u-PA was found in all melanoma cell lines. The metastatic capacity of these cell lines was studied in nude mice. All cell lines were able to develop primary tumors at the subcutaneous inoculation site. The production of plasminogen activators, their inhibitors and urokinase receptor by subcutaneous tumors corresponded with the production by the parental cell lines in vitro. The two u-PA and PAI-1 producing cell lines showed the highest frequency to form spontaneous lung metastases after subcutaneous inoculation, whereas five of the six cell lines formed lung colonies after intravenous inoculation. In conclusion, u-PA mediated matrix degradation in vitro and production of u-PA and PAI-1 by human melanoma cell lines correlated with their ability to form spontaneous lung metastasis in nude mice. No correlation was found with the ability to form lung colonies after intravenous injection. These findings suggest a role for u-PA and PAI-1 in a relatively early stage of melanoma metastasis. PMID- 1918137 TI - The complete primary structure of type XII collagen shows a chimeric molecule with reiterated fibronectin type III motifs, von Willebrand factor A motifs, a domain homologous to a noncollagenous region of type IX collagen, and short collagenous domains with an Arg-Gly-Asp site. AB - Extracellular matrix molecules are generally categorized as collagens, elastin, proteoglycans, or other noncollagenous structural/cell interaction proteins. Many of these extracellular proteins contain distinctive repetitive modules, which can sometimes be found in other proteins. We describe the complete primary structure of an alpha 1 chain of type XII collagen from chick embryonic fibroblasts. This large, structurally chimeric molecule identified by cDNA analysis combines previously unrelated molecular domains into a single large protein 3,124 residues long (approximately 340 kD). The deduced chicken type XII collagen sequence starts at the amino terminus with one unit of the type III motif of fibronectin, which is followed by one unit homologous to the von Willebrand factor A domain, then one more fibronectin type III module, a second A domain from von Willebrand factor, 6 units of type III motif and a third A domain, 10 consecutive units of type III motif and a fourth A domain, a domain homologous to the NC4 domain peptide of type IX collagen, and finally two short collagenous regions previously described as part of the partially sequenced collagen type XII molecule; an Arg Gly-Asp potential cell adhesive recognition sequence is present in a hydrophilic region at the terminus of one collagenous domain. Antibodies raised to type XII collagen synthesized in a bacterial expression system recognized not only previously reported bands (220 kD et cetera) in tendons, but also bands with apparently different molecular sizes in fibroblasts and 4-d embryos. The antibodies stained a wide variety of extracellular matrices in embryos in patterns distinct from those of fibronectin or interstitial collagens. They prominently stained extracellular matrix associated with certain neuronal tissues, such as axons from dorsal root ganglia and neural tube. These studies identify a novel chimeric type of molecule that contains both adhesion molecule and collagen motifs in one protein. Its structure blurs current classification schemes for extracellular proteins and underscores the potentially large diversity possible in these molecules. PMID- 1918139 TI - Calcium transients during Fc receptor-mediated and nonspecific phagocytosis by murine peritoneal macrophages. AB - Studies with populations of macrophages have produced conflicting results concerning the possibility that the concentration of intracellular ionized calcium [( Ca2+]i) may act as an important mediator for phagocytosis. Since asynchronous changes in [Ca2+]i in individual cells undergoing phagocytosis may be averaged to undetectability in population studies, we studied single adhering murine macrophages using fura-2 and our previously described digital imaging system. The proportion of macrophages phagocytosing IgG-coated latex beads was greater than for uncoated beads (percent phagocytosing cells: 71 +/- 7 vs. 27 +/- 7, P less than 0.01). Phagocytosis of IgG-coated and uncoated beads was always associated with a calcium transient that preceded the initiation of phagocytosis. No calcium transients were detected in cells that bound but did not phagocytose beads. Four major differences between Fc receptor-mediated and nonspecific phagocytosis were detected: (a) the duration of calcium transients was longer for nonspecific phagocytosis compared with Fc receptor-mediated phagocytosis (69.9 +/ 10.2 vs. 48.7 +/- 4.7 s, P less than 0.05) and the magnitude of calcium transients was less for nonspecific phagocytosis (178 +/- 43 vs. 349 +/- 53 nM, P less than 0.05); (b) removal of extracellular calcium abolished the calcium transients associated with nonspecific phagocytosis but had no effect on those associated with receptor-mediated phagocytosis; (c) in the absence of extracellular calcium, buffering intracellular calcium with a chelator reduced Fc receptor-mediated phagocytosis but had no additive inhibitory effect on nonspecific phagocytosis; and (d) inhibition of protein kinase C (PKC) with staurosporine inhibited nonspecific phagocytosis but had no effect on receptor mediated phagocytosis. Our observations suggest that despite both types of phagocytosis being associated with intracellular calcium transients, the role played by intracellular calcium in the signaling pathways may differ for Fc receptor-mediated and nonspecific phagocytosis by elicited murine macrophages. PMID- 1918140 TI - Dual-view microscopy with a single camera: real-time imaging of molecular orientations and calcium. AB - A new microscope technique, termed "W" (double view video) microscopy, enables simultaneous observation of two different images of an object through a single video camera or by eye. The image pair may, for example, be transmission and fluorescence, fluorescence at different wavelengths, or mutually perpendicular components of polarized fluorescence. Any video microscope can be converted into a dual imager by simple insertion of a small optical device. The continuous appearance of the dual image assures the best time resolution in existing and future video microscopes. As an application, orientations of actin protomers in individual, moving actin filaments have been imaged at the video rate. Asymmetric calcium influxes into a cell exposed to an intense electric pulse have also been visualized. PMID- 1918138 TI - Rab1b regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments. AB - We report an essential role for the ras-related small GTP-binding protein rab1b in vesicular transport in mammalian cells. mAbs detect rab1b in both the ER and Golgi compartments. Using an assay which reconstitutes transport between the ER and the cis-Golgi compartment, we find that rab1b is required during an initial step in export of protein from the ER. In addition, it is also required for transport of protein between successive cis- and medial-Golgi compartments. We suggest that rab1b may provide a common link between upstream and downstream components of the vesicular fission and fusion machinery functioning in early compartments of the secretory pathway. PMID- 1918141 TI - The influence of afferent lymphatic vessel interruption on vascular addressin expression. AB - Tissue-selective lymphocyte homing is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. These vessels, the post capillary high endothelial venules (HEV), are found in organized lymphoid tissues, and at sites of chronic inflammation. Lymphocytes bearing specific receptors, called homing receptors, recognize and adhere to their putative ligands on high endothelial cells, the vascular addressins. After adhesion, lymphocytes enter organized lymphoid tissues by migrating through the endothelial cell wall. Cells and/or soluble factors arriving in lymph nodes by way of the afferent lymph supply have been implicated in the maintenance of HEV morphology and efficient lymphocyte homing. In the study reported here, we assessed the influence of afferent lymphatic vessel interruption on lymph node composition, organization of cellular elements; and on expression of vascular addressins. At 1 wk after occlusion of afferent lymphatic vessels, HEV became flat walled and expression of the peripheral lymph node addressin disappeared from the luminal aspect of most vessels, while being retained on the abluminal side. In addition, an HEV-specific differentiation marker, defined by mAb MECA-325, was undetectable at 7-d postocclusion. In vivo homing studies revealed that these modified vessels support minimal lymphocyte traffic from the blood. After occlusion, we observed dramatic changes in lymphocyte populations and at 7-d postsurgery, lymph nodes were populated predominantly by cells lacking the peripheral lymph node homing receptor LECAM-1. In addition, effects on nonlymphoid cells were observed: subcapsular sinus macrophages, defined by mAb MOMA-1, disappeared; and interdigitating dendritic cells, defined by mAb NLDC-145, were dramatically reduced. These data reveal that functioning afferent lymphatics are centrally involved in maintaining normal lymph node homeostasis. PMID- 1918142 TI - Posttranslational processing of the prohormone-cleaving Kex2 protease in the Saccharomyces cerevisiae secretory pathway. AB - The Kex2 protease of the yeast Saccharomyces cerevisiae is a prototypical eukaryotic prohormone-processing enzyme that cleaves precursors of secreted peptides at pairs of basic residues. Here we have established the pathway of posttranslational modification of Kex2 protein using immunoprecipitation of the biosynthetically pulse-labeled protein from a variety of wild-type and mutant yeast strains as the principal methodology. Kex2 protein is initially synthesized as a prepro-enzyme that undergoes cotranslational signal peptide cleavage and addition of Asn-linked core oligosaccharide and Ser/Thr-linked mannose in the ER. The earliest detectable species, I1 (approximately 129 kD), undergoes rapid amino terminal proteolytic removal of a approximately 9-kD pro-segment yielding species I2 (approximately 120 kD) before arrival at the Golgi complex. Transport to the Golgi complex is marked by extensive elaboration of Ser/Thr-linked chains and minor modification of Asn-linked oligosaccharide. During the latter phase of its lifetime, Kex2 protein undergoes a gradual increase in apparent molecular weight. This final modification serves as a marker for association of Kex2 protease with a late compartment of the yeast Golgi complex in which it is concentrated about 27-fold relative to other secretory proteins. PMID- 1918143 TI - The small GTP-binding protein Rho1p is localized on the Golgi apparatus and post Golgi vesicles in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae the ras-related protein Rho1p is essentially the only target for ADP-ribosylation by exoenzyme C3 of Clostridium botulinum. Using C3 to detect Rho1p in subcellular fractions, Rho1p was found primarily in the 10,000 g pellet (P2) containing large organelles; small amounts also were detected in the 100,000 g pellet (P3), and cytosol. When P2 organelles were separated in sucrose density gradients Rho1p comigrated with the Kex-2 activity, a late Golgi marker. Rho1p distribution was shifted from P2 to P3 in several mutants that accumulate post-Golgi vesicles. Rho1p comigrated with post-Golgi transport vesicles during fractionation of P3 organelles from wild-type or sec6 cells. Vesicles containing Rho1p were of the same size but different density than those bearing Sec4p, a ras related protein located both on post-Golgi vesicles and the plasma membrane. Immunofluorescence microscopy detected Rho1p as a punctate pattern, with signal concentrated towards the cell periphery and in the bud. Thus, in S. cerevisiae Rho1p resides primarily in the Golgi apparatus, and also in vesicles that are likely to be early post-Golgi vesicles. PMID- 1918144 TI - Physiologically active chloroplasts contain pools of unassembled extrinsic proteins of the photosynthetic oxygen-evolving enzyme complex in the thylakoid lumen. AB - The oxygen-evolving complex (OEC) of photosystem II (PS II) consists of at least three extrinsic membrane-associated protein subunits, OE33, OE23, and OE17, with associated Mn2+, Ca2+, and Cl- ions. These subunits are bound to the lumen side of PS II core proteins embedded in the thylakoid membrane. Our experiments reveal that a significant fraction of each subunit is normally present in unassembled pools within the thylakoid lumen. This conclusion was supported by immunological detection of free subunits after freshly isolated pea thylakoids were fractionated with low levels of Triton X-100. Plastocyanin, a soluble lumen protein, was completely released from the lumen by 0.04% Triton X-100. This gentle detergent treatment also caused the release from the thylakoids of between 10 and 20%, 40 and 60%, and 15 and 50% of OE33, OE23, and OE17, respectively. Measurements of the rates of oxygen evolution from Triton-treated thylakoids, both in the presence and absence of Ca2+, and before and after incubation with hydroquinone, demonstrated that the OEC was not dissociated by the detergent treatment. Thylakoids isolated from spinach released similar amounts of extrinsic proteins after Triton treatment. These data demonstrate that physiologically active chloroplasts contain significant pools of unassembled extrinsic OEC polypeptide subunits free in the lumen of the thylakoids. PMID- 1918145 TI - Microtubule behavior in the growth cones of living neurons during axon elongation. AB - To understand how microtubules are generated in the growth cone, we have imaged fluorescently tagged microtubules in living frog embryonic neurons. The neurons were labeled by injecting rhodamine-labeled tubulin into the fertilized egg and explanting the neurons from the neural tube. Microtubules extend deep into the growth cone periphery and adopt three characteristic distributions: (a) dispersed and splayed throughout much of the growth cone; (b) looped and apparently contorted by compression; and (c) bundled into tight arrays. These distributions interconvert on a time scale of several minutes and these interconversions are correlated with the behavior of the growth cone. We observed microtubule growth and shrinkage in growth cones, but are unable to determine their contribution to net assembly. However, translocation of polymer form the axon appears to be a major mechanism of generating new polymer in the growth cone, while bundling of microtubules in the growth cone appears to be the critical step in generating new axon. Neurons that were about to turn spontaneously generated microtubules in the future direction of growth, suggesting that orientation of microtubules might be an important early step in neuronal pathfinding. PMID- 1918147 TI - Filensin: a new vimentin-binding, polymerization-competent, and membrane associated protein of the lens fiber cell. AB - We have studied the molecular properties of a 100-kD protein, termed filensin, which we have isolated from porcine lens membranes. Filensin represents a membrane-associated element, resistant to salt and nonionic detergent treatment, and extractable only by alkali or high concentrations of urea. By indirect immunofluorescence and immunoelectron microscopy, this protein can be localized at the periphery of the lens fiber cells. Immunochemical analysis suggests that filensin originates from a larger 110-kD component which is abundantly expressed in lens but not in other tissues. Purified filensin polymerizes in a salt dependent fashion and forms irregular fibrils (integral of 10 nm in diameter) when reconstituted into buffers of physiological ionic strength and neutral pH. Radiolabeled filensin binds specifically to lens vimentin under isotonic conditions, as demonstrated by affinity chromatography and ligand-blotting assays. By the latter approach, filensin also reacts with a 47-kD peripheral membrane protein of the lens cells. Purified filensin binds to PI, a synthetic peptide modelled after a segment of the COOH-terminal domain of peripherin (a type III intermediate filament protein highly homologous to vimentin), but not to various other peptides including the NH2-terminal headpiece of vimentin and derivatives of its middle (rod) domain. The filensin-PI binding is inhibited by purified lamin B, which is known to interact in vitro with PI (Djabali, K., M.-M. Portier, F. Gros, G. Blobel, and S. D. Georgatos. 1991. Cell. 64:109-121). Finally, limited proteolysis indicates that the filensin-vimentin interaction involves a 30-kD segment of the filensin molecule. Based on these observations, we postulate that the lens fiber cells express a polymerization-competent protein which is tightly associated with the plasma membrane and has the potential to serve as an anchorage site for vimentin intermediate filaments. PMID- 1918146 TI - Microtubule behavior during guidance of pioneer neuron growth cones in situ. AB - The growth of an axon toward its target results from the reorganization of the cytoskeleton in response to environmental guidance cues. Recently developed imaging technology makes it possible to address the effect of such cues on the neural cytoskeleton directly. Although high resolution studies can be carried out on neurons in vitro, these circumstances do not recreate the complexity of the natural environment. We report here on the arrangement and dynamics of microtubules in live neurons pathfinding in response to natural guidance cues in situ using the embryonic grasshopper limb fillet preparation. A rich microtubule network was present within the body of the growth cone and normally extended into the distal growth cone margin. Complex microtubule loops often formed transiently within the growth cone. Branches both with and without microtubules were regularly observed. Microtubules did not extend into filopodia. During growth cone steering events in response to identified guidance cues, microtubule behaviour could be monitored. In turns towards guidepost cells, microtubules selectively invaded branches derived from filopodia that had contacted the guidepost cell. At limb segment boundaries, microtubules displayed a variety of behaviors, including selective branch invasion, and also invasion of multiple branches followed by selective retention in branches oriented in the correct direction. Microtubule invasion of multiple branches also was seen in growth cones migrating on intrasegmental epithelium. Both selective invasion and selective retention generate asymmetrical microtubule arrangements within the growth cone, and may play a key role in growth cone steering events. PMID- 1918148 TI - The subcellular distribution of dystrophin in mouse skeletal, cardiac, and smooth muscle. AB - We use a highly specific and sensitive antibody to further characterize the distribution of dystrophin in skeletal, cardiac, and smooth muscle. No evidence for localization other than at the cell surface is apparent in skeletal muscle and no 427-kD dystrophin labeling was detected in sciatic nerve. An elevated concentration of dystrophin appears at the myotendinous junction and the neuromuscular junction, labeling in the latter being more intense specifically in the troughs of the synaptic folds. In cardiac muscle the distribution of dystrophin is limited to the surface plasma membrane but is notably absent from the membrane that overlays adherens junctions of the intercalated disks. In smooth muscle, the plasma membrane labeling is considerably less abundant than in cardiac or skeletal muscle and is found in areas of membrane underlain by membranous vesicles. As in cardiac muscle, smooth muscle dystrophin seems to be excluded from membrane above densities that mark adherens junctions. Dystrophin appears as a doublet on Western blots of skeletal and cardiac muscle, and as a single band of lower abundance in smooth muscle that corresponds most closely in molecular weight to the upper band of the striated muscle doublet. The lower band of the doublet in striated muscle appears to lack a portion of the carboxyl terminus and may represent a dystrophin isoform. Isoform differences and the presence of dystrophin on different specialized membrane surfaces imply multiple functional roles for the dystrophin protein. PMID- 1918149 TI - Cytoplasmic components of acetylcholine receptor clusters of cultured rat myotubes: the 58-kD protein. AB - A 58-kD protein, identified in extracts of postsynaptic membrane from Torpedo electric organ, is enriched at sites where acetylcholine receptors (AChR) are concentrated in vertebrate muscle (Froehner, S. C., A. A. Murnane, M. Tobler, H. B. Peng, and R. Sealock. 1987. J. Cell Biol. 104:1633-1646). We have studied the 58-kD protein in AChR clusters isolated from cultured rat myotubes. Using immunofluorescence microscopy we show that the 58-kD protein is highly enriched at AChR clusters, but is also present in regions of the myotube membrane lacking AChR. Within clusters, the 58-kD protein codistributes with AChR, and is absent from adjacent membrane domains involved in myotube-substrate contact. Semiquantitative fluorescence measurements suggest that molecules of the 58-kD protein and AChR are present in approximately equal numbers. Differential extraction of peripheral membrane proteins from isolated AChR clusters suggests that the 58-kD protein is more tightly bound to cluster membrane than is actin or spectrin, but less tightly bound than the receptor-associated 43-kD protein. When AChR clusters are disrupted either in intact cells or after isolation, the 58-kD protein still codistributes with AChR. Clusters visualized by electron microscopy after immunogold labeling and quick-freeze, deep-etch replication show that, within AChR clusters, the 58-kD protein is sharply confined to AChR-rich domains, where it is present in a network of filaments lying on the cytoplasmic surface of the membrane. Additional actin filaments overlie, and are attached to, this network. Our results suggest that within AChR domains of clusters, the 58-kD protein lies between AChR and the receptor-associated 43-kD protein, and the membrane-skeletal proteins, beta-spectrin, and actin. PMID- 1918150 TI - Regional distribution, developmental changes, and cellular localization of CNTF mRNA and protein in the rat brain. AB - Ciliary neurotrophic factor (CNTF) is a potent survival molecule for a variety of embryonic neurons in culture. The developmental expression of CNTF occurs clearly after the time period of the physiological cell death of CNTF-responsive neurons. This, together with the sites of expression, excludes CNTF as a target-derived neuronal survival factor, at least in rodents. However, CNTF also participates in the induction of type 2 astrocyte differentiation in vitro. Here we demonstrate that the time course of the expression of CNTF-mRNA and protein in the rat optic nerve (as evaluated by quantitative Northern blot analysis and biological activity, respectively) is compatible with such a glial differentiation function of CNTF in vivo. We also show that the type 2 astrocyte-inducing activity previously demonstrated in optic nerve extract can be precipitated by an antiserum against CNTF. Immunohistochemical analysis of astrocytes in vitro and in vivo demonstrates that the expression of CNTF is confined to a subpopulation of type 1 astrocytes. The olfactory bulb of adult rats has comparably high levels of CNTF to the optic nerve, and here again, CNTF-immunoreactivity is localized in a subpopulation of astrocytes. However, the postnatal expression of CNTF in the olfactory bulb occurs later than in the optic nerve. In other brain regions both CNTF-mRNA and protein levels are much lower. PMID- 1918152 TI - A role for the E-cadherin cell-cell adhesion molecule during tumor progression of mouse epidermal carcinogenesis. AB - The expression of the cell-cell adhesion molecules E- and P-cadherin has been analyzed in seven mouse epidermal keratinocyte cell lines representative of different stages of epidermal carcinogenesis. An inverse correlation between the amount of E-cadherin protein and tumorigenicity of the cell lines has been found, together with a complete absence of E-cadherin protein and mRNA expression in three carcinoma cell lines (the epithelioid HaCa4 and the fibroblastoid CarB and CarC cells). A similar result has been detected in tumors induced in nude mice by the cell lines, where induction of E-cadherin expression takes place in moderately differentiated squamous cell carcinomas induced by HaCa4 cells, although at much lower levels than in well-differentiated tumors induced by the epithelial PDV or PDVC57 cell lines. Complete absence of E-cadherin expression has been observed in spindle cell carcinomas induced by CarB or CarC cells. P cadherin protein was detected in all cell lines that exhibit an epithelial (MCA3D, AT5, PDV, and PDVC57) or epithelioid (HaCa4) morphology, as well as in nude mouse tumors, independent of their tumorigenic capabilities. However, complete absence of P-cadherin was observed in the fibroblast-like cells (CarB and CarC) and in spindle cell carcinomas. The introduction of an exogenous E cadherin cDNA into HaCa4 cells, or reactivation of the endogenous E-cadherin gene, leads to a partial suppression of the tumorigenicity of this highly malignant cell line. These results suggest a role for E-cadherin in the progression to malignancy of mouse epidermal carcinogenesis. They also suggest that the loss of both E- and P-cadherin could be associated to the final stage of carcinogenesis, the development of spindle cell carcinomas. PMID- 1918151 TI - A plasma membrane protein is involved in cell contact-mediated regulation of tissue-specific genes in adult hepatocytes. AB - We have identified the liver-regulating protein (LRP), a cell surface protein involved in the maintenance of hepatocyte differentiation when cocultured with rat liver epithelial cells (RLEC). LRP was defined by immunoreactivity to a monoclonal antibody (mAb L8) prepared from RLEC. mAb L8 specifically detected two polypeptides of 85 and 73 kD in immunoprecipitation of both hepatocyte- and RLEC iodinated plasma membranes. The involvement of these polypeptides, which are integral membrane proteins, in cell interaction-mediated regulation of hepatocytes was assessed by evaluating the perturbing effects of the antibody on cocultures with RLEC. Several parameters characteristic of differentiated hepatocytes were studied, such as liver-specific and house-keeping gene expression, cytoskeletal organization and deposition of extracellular matrix (ECM). An early cytoskeletal disturbance was evidenced and a marked alteration of hepatocyte functional capacity was observed in the presence of the antibody, together with a loss of ECM deposition. By contrast, cell-cell aggregation or cell adhesion to various extracellular matrix components were not affected. These findings suggest that LRP is distinct from an extracellular matrix receptor. The fact that early addition of mAb L8 during cell contact establishment was necessary to be effective may indicate that LRP is a novel plasma membrane protein that plays an early pivotal role in the coordinated metabolic changes which lead to the differentiated phenotype of mature hepatocytes. PMID- 1918153 TI - Expression of two nonallelic type II procollagen genes during Xenopus laevis embryogenesis is characterized by stage-specific production of alternatively spliced transcripts. AB - The pattern of type II collagen expression during Xenopus laevis embryogenesis has been established after isolating specific cDNA and genomic clones. Evidence is presented suggesting that in X. laevis there are two transcriptionally active copies of the type II procollagen gene. Both genes are activated at the beginning of neurula stage and steady-state mRNA levels progressively increase thereafter. Initially, the transcripts are localized to notochord, somites, and the dorsal region of the lateral plate mesoderm. At later stages of development and parallel to increased mRNA accumulation, collagen expression becomes progressively more confined to chondrogenic regions of the tadpole. During the early period of mRNA accumulation, there is also a transient pattern of expression in localized sites that will later not undergo chondrogenesis, such as the floor plate in the ventral neural tube. At later times and coincident with the appearance of chondrogenic tissues in the developing embryo, expression of the procollagen genes is characterized by the production of an additional, alternatively spliced transcript. The alternatively spliced sequences encode the cysteine-rich globular domain in the NH2-propeptide of the type II procollagen chain. Immunohistochemical analyses with a type II collagen monoclonal antibody documented the deposition of the protein in the extracellular matrix of the developing embryo. Type II collagen expression is therefore temporally regulated by tissue-specific transcription and splicing factors directing the synthesis of distinct molecular forms of the precursor protein in the developing Xenopus embryo. PMID- 1918154 TI - Mitotic motors. PMID- 1918155 TI - Three-dimensional reconstruction of the 70S Escherichia coli ribosome in ice: the distribution of ribosomal RNA. AB - A reconstruction, at 40 A, of the Escherichia coli ribosome imaged by cryo electron microscopy, obtained from 303 projections by a single-particle method of reconstruction, shows the two subunits with unprecedented clarity. In the interior of the subunits, a complex distribution of higher mass density is recognized, which is attributed to ribosomal RNA. The masses corresponding to the 16S and 23S components are linked in the region of the platform of the small subunit. Thus the topography of the rRNA regions responsible for protein synthesis can be described. PMID- 1918156 TI - Distinct intracellular fates of membrane and secretory immunoglobulin heavy chains in a pre-B cell line. AB - The intracellular fates of membrane and secretory immunoglobulin heavy chains were examined in a pre-B cell line that has switched to the gamma isotype. The membrane form of the heavy chain (gamma m) was rapidly degraded while the secretory form (gamma s) was retained intracellularly in association with BiP. The degradation of gamma m could not be inhibited by ammonium chloride, chloroquine, or monensin suggesting that it occurred in a nonlysosomal compartment. The inability to detect any Endo H-resistant form of gamma m before its degradation suggested that degradation occurs before entry into the Golgi compartment. Degradation of gamma m could be inhibited by incubation at 24 degrees C. In a derivative of this cell line expressing a transfected kappa gene, gamma s formed disulfide linked tetramers with kappa and was secreted, while gamma m, although associated with kappa, continued to be rapidly degraded. These observations suggest that membrane and secretory heavy chain proteins are retained by distinct intracellular mechanisms. Although masking of the CH1 domain abrogates gamma s retention, this domain does not influence the intracellular fate of gamma m. PMID- 1918157 TI - Tubular early endosomal networks in AtT20 and other cells. AB - Using horseradish peroxidase (HRP) as a fluid-phase endocytic tracer, we observed through the electron microscope numerous tubular endosomes with a diameter of 30 50 nm and lengths of greater than 2 microns in thick sections (0.2-0.5 microns) of AtT20 cells. These tubular endosomes are multibranching and form local networks but not a single reticulum throughout the cytoplasm. They are sometimes in continuity with vesicular endosomal structures but have not been observed in continuity with AtT20 cell late endosomes. Tubular endosomal networks are not uniformly distributed throughout the cytoplasm, but are particularly abundant in growth cones, in patches below the plasma membrane of the cell body, and surrounding the centrioles and microtubule organizing center (MTOC). Tubular endosomes at all these locations receive HRP within the first 5 min of endocytosis but approximately 30 min of endocytosis are required to load the tubular endosomal networks with HRP so that their full extent can be visualized in the electron microscope. After 10 min of endocytosis, complete unloading occurs within 30 min of chase, but between 30 and 60 min are required to chase out all the tracer from the tubular endosomes loaded to steady state during 60 min endocytosis of 10 mg/ml HRP. In interphase cells, neither the loading nor unloading of tubular endosomes depends on microtubules but in cells blocked in mitosis by depolymerization of the mitotic spindle with nocodazole, HRP does not chase out of tubular endosomes. The thread-like shape of tubular endosomes is not dependent on microtubules. Furthermore, HRP is delivered to AtT20 tubular endosomes at 20 degrees C. All these properties indicate that AtT20 cell tubular endosomes are an early endocytic compartment distinct from late endosomes. Tubular endosomes like those in AtT20 cells have been seen in cells of the following lines: PC12, HeLa, Hep2, Vero, MDCK I and II, CCL64, RK13, and NRK; they are particularly abundant in the first three lines. In contrast, tubular endosomes are sparse in 3T3 and BHK21 cells. The tubular endosomes we have observed appear to be identical to the endosomal reticulum observed in the living Hep2 cells by Hopkins, C. R., A. Gibson, H. Shipman, and K. Miller. 1990. PMID- 1918158 TI - Kinetic analysis of F-actin depolymerization in polymorphonuclear leukocyte lysates indicates that chemoattractant stimulation increases actin filament number without altering the filament length distribution. AB - The rate of filamentous actin (F-actin) depolymerization is proportional to the number of filaments depolarizing and changes in the rate are proportional to changes in filament number. To determine the number and length of actin filaments in polymorphonuclear leukocytes and the change in filament number and length that occurs during the increase in F-actin upon chemoattractant stimulation, the time course of cellular F-actin depolymerization in lysates of control and peptide stimulated cells was examined. F-actin was quantified by the TRITC-labeled phalloidin staining of pelletable actin. Lysis in 1.2 M KCl and 10 microM DNase I minimized the effects of F-actin binding proteins and G-actin, respectively, on the kinetics of depolymerization. To determine filament number and length from a depolymerization time course, depolymerization kinetics must be limited by the actin monomer dissociation rate. Comparison of time courses of depolymerization in the presence (pointed ends free) or absence (barbed and pointed ends free) of cytochalasin suggested depolymerization occurred from both ends of the filament and that monomer dissociation was rate limiting. Control cells had 1.7 +/- 0.4 x 10(5) filaments with an average length of 0.29 +/- 0.09 microns. Chemo-attractant stimulation for 90 s at room temperature with 0.02 microM N formylnorleucylleucylphenylalanine caused a twofold increase in F-actin and about a two-fold increase in the total number of actin filaments to 4.0 +/- 0.5 x 10(5) filaments with an average length of 0.27 +/- 0.07 microns. In both cases, most (approximately 80%) of the filaments were quite short (less than or equal to 0.18 micron). The length distributions of actin filaments in stimulated and control cells were similar. PMID- 1918159 TI - The structural basis for the intrinsic disorder of the actin filament: the "lateral slipping" model. AB - Three-dimensional (3-D) helical reconstructions computed from electron micrographs of negatively stained dispersed F-actin filaments invariably revealed two uninterrupted columns of mass forming the "backbone" of the double-helical filament. The contact between neighboring subunits along the thus defined two long-pitch helical strands was spatially conserved and of high mass density, while the intersubunit contact between them was of lower mass density and varied among reconstructions. In contrast, phalloidinstabilized F-actin filaments displayed higher and spatially more conserved mass density between the two long pitch helical strands, suggesting that this bicyclic hepta-peptide toxin strengthens the intersubunit contact between the two strands. Consistent with this distinct intersubunit bonding pattern, the two long-pitch helical strands of unstabilized filaments were sometimes observed separated from each other over a distance of two to six subunits, suggesting that the intrastrand intersubunit contact is also physically stronger than the interstrand contact. The resolution of the filament reconstructions, extending to 2.5 nm axially and radially, enabled us to reproducibly "cut out" the F-actin subunit which measured 5.5 nm axially by 6.0 nm tangentially by 3.2 nm radially. The subunit is distinctly polar with a massive "base" pointing towards the "barbed" end of the filament, and a slender "tip" defining its "pointed" end (i.e., relative to the "arrowhead" pattern revealed after stoichiometric decoration of the filaments with myosin subfragment 1). Concavities running approximately parallel to the filament axis both on the inner and outer face of the subunit define a distinct cleft separating the subunit into two domains of similar size: an inner domain confined to radii less than or equal to 2.5-nm forms the uninterrupted backbone of the two long-pitch helical strands, and an outer domain placed at radii of 2-5-nm protrudes radially and thus predominantly contributes to the outer part of the massive base. Quantitative evaluation of successive crossover spacings along individual F-actin filaments revealed the deviations from the mean repeat to be compensatory, i.e., short crossovers frequently followed long ones and vice versa. The variable crossover spacings and diameter of the F-actin filament together with the local unraveling of the two long-pitch helical strands are explained in terms of varying amounts of compensatory "lateral slipping" of the two strands past each other roughly perpendicular to the filament axis. This intrinsic disorder of the actin filament may enable the actin moiety to play a more active role in actin-myosin-based force generation than merely act as a rigid passive cable as has hitherto been assumed. PMID- 1918160 TI - Striated microtubule-associated fibers: identification of assemblin, a novel 34 kD protein that forms paracrystals of 2-nm filaments in vitro. AB - Microtubule-associated fibers from the basal apparatus of the green flagellate alga Spermatozopsis similis exhibit a complex cross-striation pattern with 28-nm periodicity and consist of 2-nm filaments arranged in several layers. Fibers enriched by mechanical disintegration and high salt extraction (2 M NaCl) of isolated basal apparatuses are soluble in 2 M urea. Dialysis of solubilized fibers against 150 mM KCl yields paracrystals which closely resemble the native fibers in filament arrangement and striation pattern. Paracrystals purified through several cycles of disassembly and reassembly are greatly enriched (greater than 90%) in a single protein of 34 kD (assemblin) as shown by SDS-PAGE. A rabbit polyclonal antibody raised against assemblin labels the striated fibers as shown by indirect immunofluorescence of isolated cytoskeletons or methanol permeabilized cells and immunogold EM. Two-dimensional electrophoresis (isoelectric focusing and SDS-PAGE) resolves assemblin into at least four isoforms (a-d) with pI's of 5.45, 5.55, 5.75, and 5.85. The two more acidic isoforms are phosphoproteins as shown by in vivo 32PO4-labeling and autoradiography. Amino acid analysis of assemblin shows a high content of helix forming residues (leucine) and a relatively low content of glycine. We conclude that assemblin may be representative of a class of proteins that form fine filaments alongside microtubules. PMID- 1918161 TI - Tau protein binds to microtubules through a flexible array of distributed weak sites. AB - Tau protein plays a role in the extension and maintenance of neuronal processes through a direct association with microtubules. To characterize the nature of this association, we have synthesized a collection of tau protein fragments and studied their binding properties. The relatively weak affinity of tau protein for microtubules (approximately 10(-7) M) is concentrated in a large region containing three or four 18 amino acid repeated binding elements. These are separated by apparently flexible but less conserved linker sequences of 13-14 amino acids that do not bind. Within the repeats, the binding energy for microtubules is delocalized and derives from a series of weak interactions contributed by small groups of amino acids. These unusual characteristics suggest tau protein can assume multiple conformations and can pivot and perhaps migrate on the surface of the microtubule. The flexible structure of the tau protein binding interaction may allow it to be easily displaced from the microtubule lattice and may have important consequences for its function. PMID- 1918162 TI - Acetylcholinesterase from the motor nerve terminal accumulates on the synaptic basal lamina of the myofiber. AB - Acetylcholinesterase (AChE) in skeletal muscle is concentrated at neuromuscular junctions, where it is found in the synaptic cleft between muscle and nerve, associated with the synaptic portion of the myofiber basal lamina. This raises the question of whether the synaptic enzyme is produced by muscle, nerve, or both. Studies on denervated and regenerating muscles have shown that myofibers can produce synaptic AChE, and that the motor nerve may play an indirect role, inducing myofibers to produce synaptic AChE. The aim of this study was to determine whether some of the AChE which is known to be made and transported by the motor nerve contributes directly to AChE in the synaptic cleft. Frog muscles were surgically damaged in a way that caused degeneration and permanent removal of all myofibers from their basal lamina sheaths. Concomitantly, AChE activity was irreversibly blocked. Motor axons remained intact, and their terminals persisted at almost all the synaptic sites on the basal lamina in the absence of myofibers. 1 mo after the operation, the innervated sheaths were stained for AChE activity. Despite the absence of myofibers, new AChE appeared in an arborized pattern, characteristic of neuromuscular junctions, and its reaction product was concentrated adjacent to the nerve terminals, obscuring synaptic basal lamina. AChE activity did not appear in the absence of nerve terminals. We concluded therefore, that the newly formed AChE at the synaptic sites had been produced by the persisting axon terminals, indicating that the motor nerve is capable of producing some of the synaptic AChE at neuromuscular junctions. The newly formed AChE remained adherent to basal lamina sheaths after degeneration of the terminals, and was solubilized by collagenase, indicating that the AChE provided by nerve had become incorporated into the basal lamina as at normal neuromuscular junctions. PMID- 1918163 TI - Relationship between neuronal migration and cell-substratum adhesion: laminin and merosin promote olfactory neuronal migration but are anti-adhesive. AB - Regulation by the extracellular matrix (ECM) of migration, motility, and adhesion of olfactory neurons and their precursors was studied in vitro. Neuronal cells of the embryonic olfactory epithelium (OE), which undergo extensive migration in the central nervous system during normal development, were shown to be highly migratory in culture as well. Migration of OE neuronal cells was strongly dependent on substratum-bound ECM molecules, being specifically stimulated and guided by laminin (or the laminin-related molecule merosin) in preference to fibronectin, type I collagen, or type IV collagen. Motility of OE neuronal cells, examined by time-lapse video microscopy, was high on laminin-containing substrata, but negligible on fibronectin substrata. Quantitative assays of adhesion of OE neuronal cells to substrata treated with different ECM molecules demonstrated no correlation, either positive or negative, between the migratory preferences of cells and the strength of cell-substratum adhesion. Moreover, measurements of cell adhesion to substrata containing combinations of ECM proteins revealed that laminin and merosin are anti-adhesive for OE neuronal cells, i.e., cause these cells to adhere poorly to substrata that would otherwise be strongly adhesive. The evidence suggests that the anti-adhesive effect of laminin is not the result of interactions between laminin and other ECM molecules, but rather an effect of laminin on cells, which alters the way in which cells adhere. Consistent with this view, laminin was found to interfere strongly with the formation of focal contacts by OE neuronal cells. PMID- 1918164 TI - ras isoprenylation is required for ras-induced but not for NGF-induced neuronal differentiation of PC12 cells. AB - We have used compactin, an inhibitor of mevalonate biosynthesis, to block p21ras posttranslational modification and membrane association in PC12 cells. Previous studies have demonstrated a requirement for isoprenylation for mitogenic effects of activated p21ras in mammalian cells and for function of RAS gene products in yeast. Immunoprecipitation of [35S]methionine-labeled p21ras from PC12 cell homogenates confirmed that the processed p21ras species is missing from compactin treated PC12 cells. Immunoprecipitation from particulate and cytosolic fractions of PC12 cells confirmed that compactin blocks p21ras membrane association: p21ras is confined to the cytosol fraction. Induction of neuronal differentiation and ornithine decarboxylase (ODCase) transcription by oncogenic p21N-ras does not occur in compactin-treated cells indicating that activity of oncogenic p21N-ras expressed in PC12 cells is abolished by compactin treatment. Thus, p21ras isoprenylation or association with the membrane appears to be required for early responses and neuronal differentiation attributable to p21ras activation. In contrast, blockade of p21ras isoprenylation and membrane association by compactin treatment did not significantly reduce PC12 cell responses to NGF. Responses examined included rapid phosphorylation of tyrosine hydroxylase, rapid induction of ODCase expression, survival in serum-free medium and neuronal differentiation. Compactin blocked growth factor-induced rapid changes in cell surface morphology but did so whether this response was induced by NGF or by EGF. These results indicate that functional p21ras is not necessary for responses to NGF which in turn implies that if a ras-dependent NGF signal transduction pathway exists, as has been previously suggested, at least one additional ras-independent pathway must also be present. PMID- 1918167 TI - Abstracts of papers presented at the thirty-first annual meeting of The American Society for Cell Biology. 8-12 December 1991, Boston, Massachusetts. PMID- 1918166 TI - Endothelins produced by endothelial cells promote collagen gel contraction by fibroblasts. AB - Endothelial 1 (E1) is identified as an endothelial cell secreted factor that stimulates collagen gel contraction by fibroblasts. This identification is based on (a) co-localization of stimulatory activity in endothelial cell conditioned media with synthetic E1 in reversed phase analysis; (b) removal of the activity from conditioned media with antiserum directed against E1; and (c) the activity of synthetic E1. Treatment of endothelial cell conditioned media with immobilized anti-E1 antibodies removed 59% of the activity from the pool suggesting that E1 is the major contraction promoter in endothelial cell conditioned medium. The mechanism of action of E1 is shown to be different from serum in that E1-promoted contraction is dependent upon the synthesis of an unknown effector protein. Synthetic E1 is shown to be a potent promoter of gel contraction with half maximal activity occurring at 32 pM. Two other endothelins, E2 and VIC, are slightly less active than E1. A fourth endothelin species, E3, is substantially less active. A comparison of E1 with other contraction promoting peptides revealed that E1 and platelet-derived growth factor are essentially equal in specific activity, whereas TGF beta is approximately 50-fold more potent. PMID- 1918168 TI - Differential expression of two classes of lck transcripts upon phorbol ester treatment of human leukemic T cells. AB - The human lymphocyte-specific tyrosine kinase gene, lck, is transcribed from two distinct promoters, resulting in two classes of transcripts (type I and II) differing in their 5' untranslated regions. The steady-state levels of the type I and II lck transcripts were measured in a variety of lymphoid and non-lymphoid human tumor cell lines by S1 nuclease mapping and by a sensitive assay system using the polymerase chain reaction. Human thymocytes and all the leukemic T cell lines tested express both type I and II lck transcripts, albeit at different relative levels. Peripheral blood T cells express mainly type II lck transcripts, whereas two colonic carcinoma lines, COLO 201 and COLO 205, express exclusively type I lck transcripts. Treatment of the leukemic T cell lines, P30/OKUBO and Jurkat, by the phorbol esters tetradecanoylphorbol acetate (TPA) or phorbol dibutyrate (PDB) results in the down-regulation of the type I, and the up regulation of the type II, lck transcript levels. The effect of PDB on the in vitro differentiation of Jurkat cells, and the expression of lck transcripts, is reversible. The modulation of lck transcript levels in TPA-treated Jurkat cells is not due to differential RNA stability, suggesting that the two lck promoters are utilized differentially during T cell differentiation. The leukemic T cell line, Jurkat, may thus serve as a model for the elucidation of molecular mechanisms that regulate lck transcription and T cell differentiation. PMID- 1918165 TI - Expression of beta 1, beta 3, beta 4, and beta 5 integrins by human epidermal keratinocytes and non-differentiating keratinocytes. AB - We have compared the adhesive properties and integrin expression profiles of cultured human epidermal keratinocytes and a strain of nondifferentiating keratinocytes (ndk). Both cell types adhered to fibronectin, laminin, and collagen types I and IV, but ndk adhered more rapidly and at lower coating concentrations of the proteins. Antibody blocking experiments showed that adhesion of both cell types to fibronectin was mediated by the alpha 5 beta 1 integrin and to laminin by alpha 3 beta 1 in synergy with alpha 2 beta 1. Keratinocytes adhered to collagen with alpha 2 beta 1, but an antibody to alpha 2 did not inhibit adhesion of ndk to collagen. Both cell types adhered to vitronectin by alpha v-containing integrins. Immunoprecipitation of surface iodinated and metabolically labeled cells showed that in addition to alpha 2 beta 1, alpha 3 beta 1, and alpha 5 beta 1, both keratinocytes and ndk expressed alpha 6 beta 4 and alpha v beta 5. ndk expressed all these integrins at higher levels than normal keratinocytes. ndk, but not normal keratinocytes, expressed alpha v beta 1 and alpha v beta 3; they also expressed alpha 1 beta 1, an integrin that was not consistently detected on normal keratinocytes. Immunofluorescence experiments showed that in stratified cultures of normal keratinocytes integrin expression was confined to cells in the basal layer; terminally differentiating cells were unstained. In contrast, all cells in the ndk population were integrin positive. Our observations showed that the adhesive properties of ndk differ from normal keratinocytes and reflect differences in the type of integrins expressed, the level of expression and the distribution of integrins on the cell surface. ndk thus have a number of characteristics that distinguish them from normal basal keratinocytes. PMID- 1918170 TI - Transforming activity of mutant human p53 alleles. AB - Mutant forms of the p53 gene have been shown to cooperate with an activated ras gene in transforming primary cells in culture. The aberrant proteins encoded by p53 mutants are thought to act in a dominant negative manner in these assays. In vivo data, however, reveal that where p53 has undergone genetic change in tumors, both alleles have been affected. We previously identified a case of human acute myelogenous leukemia (AML) in which both alleles of the p53 gene had undergone independent missense mutations (at codons 135 cys to ser and 246 met to val). In these blasts, p53 mutations appear to be acting recessively. We have assayed the transforming potential of these p53 mutations, as well as that of another mutation at codon 273, also identified in a human neoplasm. Both mutations from the AML blasts (codon 135 and codon 246) confer transforming ability on the mutant protein. While transformation assays may define functionally different subsets of p53 mutations, the overexpression phenotype of mutants in this assay may not accurately reflect the pathological effects of p53 mutations in vivo. PMID- 1918169 TI - Interleukin-6 production by the blast cells of acute myeloblastic leukemia: regulation by endogenous interleukin-1 and biological implications. AB - Coordinate production of interleukin-1 beta (IL-1 beta) and granulocyte macrophage-colony stimulating factor (GM-CSF) or IL-6 by the blast cells of acute myeloblastic leukemia (AML) and normal peripheral blood leukocytes have been previously reported (van der Shoot et al.: Blood 74:2081-2087, 1989; Bradbury et al.: Leukemia 4:44-47 1990a, British Journal of Haematology 16:(in press), 1990b; Rodriguez-Cimadevilla et al.: Blood 76:1481-1489, 1990; Schindler et al.: Blood 75:40-47, 1990). In the present study, we show that IL-6 production by AML blasts is up-regulated by endogenously produced IL-1 beta. Neutralization of the endogenous source of IL-1 results in a significant decrease in IL-6 production, as determined by ELISA. Conversely, exposure of AML blasts to IL-1 alpha results in a significant increase in IL-6 production in 10 of 16 patient samples. Antibodies against IL-1 alpha and -beta also cause a drastic decrease in IL-6 and GM-CSF gene expression by the cells, suggesting that cytokine gene expression in AML blasts is driven, at least in part, by endogenous IL-1. The biologic significance of IL-6 production in culture of AML blasts has been addressed using a neutralizing antibody against IL-6. Our data indicate that IL-6 is important for the survival of clonogenic blasts in culture. In contrast, the survival of the total population of blasts is IL-6-independent, as assessed by the integrity of cellular DNA, even in the presence of anti-IL-6. These observations are consistent with the view that AML blasts might be organized as a lineage, with comparable hierarchy as in normal hemopoiesis and, perhaps, increased heterogeneity despite a homogenous appearance (McCulloch and Till: Blood Cells 7:63-77, 1981; Buick and McCulloch: Control of Animal Cell Proliferation. Academic Press, New York, vol. 1, pp. 25-57, 1985). Buick and McCulloch have identified a subpopulation of AML clonogenic cells with stem-cell-like properties, and suggested that the majority of blasts may have undergone a determination-like step. Our data indicate a marked difference in IL-6 requirement for cell survival between precursors and the majority of blasts, suggesting that IL-6 responsiveness may decrease following a determination-like event, i.e., the reduction in proliferative capacity. PMID- 1918171 TI - Regulation of interleukin-6 expression in the lymphoma cell line OCI-LY3. AB - Previously we described a cell line OCI-LY3 derived from a patient with non Hodgkin's lymphoma. The cell line produced interleukin-6 (IL-6) mRNA and protein and demonstrated an autocrine pattern of growth for IL-6. Southern blot analysis of the IL-6 gene did not reveal any rearrangement. To determine whether the production of IL-6 by OCI-LY3 was due to subtle changes in the promoter of IL-6 or due to the expression of trans-acting factors chloramphenicol acetyltransferase (CAT) reporter constructs containing from -1,180 to +13 to -112 to +13 of a normal IL-6 gene were electroporated into the cell line. When these constructs are transferred into unstimulated fibroblasts, no CAT activity is seen; however, CAT activity is induced when the cells are stimulated with either IL-1 alpha, lipopolysaccharide (LPS), or cyclic adenosine monophosphate (cAMP) analogues. When the cell line OCI-LY3 was transfected with these constructs, CAT activity was observed; it was not necessary to stimulate the cells with exogenous factors to observe this activity. No CAT activity was observed in a second lymphoma cell line, OCI-LY13.1, that does not produce IL-6. These results suggest that the constitutive production of IL-6 by the cell line OCI-LY3 is due to the presence of trans-acting factors that stimulate the expression of IL-6 and not due to a cis-acting mutation of the IL-6 promoter. PMID- 1918173 TI - Erythroid lineage-specific activity in conditioned medium derived from cloned human marrow stromal cells (CFU-RF). AB - Using long-term culture techniques, it has been shown that stromal cells in the marrow microenvironment are essential for the continued production and self renewal of hematopoietic stem cells. We previously reported the development of a methylcellulose colony assay for a population of marrow stromal progenitors called CFU-RF. In this paper, a method is described for subculturing cells from individual CFU-RF-derived colonies to allow conditioned medium production (StCM). StCM, prepared in this way, was found to possess an erythroid lineage-specific activity that stimulated the formation of macroscopic erythroid colonies in cultures containing erythropoietin (epo). Using dose-response curves, the KG1 colony assay, and antibody neutralization, it was shown that the activity could not be attributed to interleukin 3 (IL3) or granulocyte-macrophage colony stimulating factor (GM-CSF). However, it was further shown that a monolayer of stromal cells, which had earlier been producing the erythroid activity, could be stimulated by IL1 to produce granulocytic colony-stimulating activity, but only as long as IL1 was present in the culture medium. These findings indicate a mechanism whereby the same stromal population could be modulated to promote growth and differentiation of different hematopoietic lineages. PMID- 1918172 TI - Clearance and fate of leukemia-inhibitory factor (LIF) after injection into mice. AB - Leukemia-inhibitory factor (LIF) elicits effects on a broad range of cell types, including cells of the monocytic and megakaryocytic series, embryonal stem cells, hepatocytes, adipocytes, and osteoblasts. Native and recombinant LIF, injected intravenously into adult mice, had an initial half-life of 6-8 min and a more prolonged second clearance phase. Clearance of 125I-LIF from the circulation was paralleled by a rapid accumulation in the kidneys, liver, lungs, and spleen and a more gradual accumulation in the thyroid gland. Labeling of the renal glomerular tufts, parenchymal hepatocytes, splenic red pulp, alveolar pneumocytes, and thyroid follicular cells as well as of megakaryocytes and osteoblasts in the bone cavities, placental trophoblasts, and cells of the choroid plexus was demonstrable autoradiographically. The appearance of a large amount of nonprecipitable 125I in the urine suggested that the kidneys were the major route of LIF clearance from the body. PMID- 1918175 TI - Dependence of mouse thymocyte-erythrocyte rosette formation on complete identity at class-I-MHC. AB - Mouse thymocytes and erythrocytes form rosettes when incubated together at 4 degrees C. The frequency is much higher when the thymocytes and erythrocytes are MHC-identical. If the indolizidine alkaloid swainsonine (SW) is present during rosette formation at concentrations of 1 microgram/ml (5.7 microM) or greater, rosette formation between MHC-identical pairs is inhibited to levels comparable to those observed for MHC-different pairs; rosette formation by MHC-different pairs is not affected. This was confirmed by examining 17 different MHC-identical combinations (9 completely syngeneic and 8 differing in non-MHC genes) and 13 MHC different combinations (3 of these identical everywhere except at MHC). A SW inhibitable component of rosette formation was observed only when thymocyte and erythrocyte were completely identical at MHC. Thus F1-parent pairs behaved as if allogeneic, although both F1-F1 and parent-parent had a SW-inhibitable rosetting component. Similarly, inbred strains only partially MHC-identical (B10.BR-B10.A, B10.D2-B10.A) behaved as if allogeneic. The SW-inhibitable component of rosetting could be partially but significantly blocked by including monoclonal antibodies against Thy-1, and anti-CD4 plus anti-CD8 (together but not separately); anti class-I-MHC produced some inhibition of marginal significance. Monoclonal antibodies against class-I-MHC, LFA-1, and CD3 did not block. Pretreatment of erythrocytes with neuraminidase, greatly reduced the SW-inhibitable component of rosetting. The SW effect would appear to be due to a direct interaction of SW with a cell surface structure involved in syngeneic rosette formation rather than the known ability of SW to block the processing of N-linked sugar structures. The results are consistent with cell surface lectins and cell surface sugars playing a role in rosette formation. PMID- 1918174 TI - DNA-mediated transfer of a human gene that confers resistance to mitomycin C. AB - Attempts to complement the defect in the mitomycin C (MMC)-sensitive Chinese hamster ovary (CHO) mutant MMC3 led to the isolation of hybrids with high resistance to the cytotoxic action of the drug. Hybrid cells selected with MMC after fusion of MMC3 cells to human diploid fibroblasts were approximately five times more resistant to MMC than wild-type CHO cells but retained the original MMC3 sensitivity to another DNA cross-linking agent, diepoxybutane. To confirm that the MMC resistance was genetically determined and was of human origin, DNA from the resistant hybrids was introduced into MMC3 cells, and transfectants were selected in MMC. These cells had the same level of MMC resistance as the hybrids. Thus we have identified a human gene that can confer MMC resistance to CHO cells. Identification of the gene should help understand the mechanisms of MMC resistance in mammalian cells. PMID- 1918176 TI - A new perspective on ornithine decarboxylase regulation: prevention of polyamine toxicity is the overriding theme. AB - The polyamines are essential cellular components for growth. Control of a key regulated enzyme of polyamine biosynthesis, ornithine decarboxylase (ODC), as a function of growth, is an area of intense interest. A unique regulatory property of ODC is the short half-life of the protein, which has been suggested to be an important factor in rapid activation of polyamine biosynthesis after cells are mitogenically stimulated. In this paper, it is argued that the biological significance of the short half-life of ODC is unrelated to the rate of its induction to a new steady state by growth factors, which is in fact limited by the relatively long half-life of the ODC mRNA. Instead, I suggest that the rapid turnover of ODC protein becomes of significance when cells cease growth and expeditious downregulation of the enzyme is important in preventing polyamine overproduction, which would result in cytotoxicity in the arrested cells. Although mitogenic activation of ODC expression has been studied extensively, there is very little known about the mechanisms controlling downregulation of polyamine biosynthesis during the arrest of animal cell growth. These considerations suggest that this would be a fertile area of future inquiry. PMID- 1918177 TI - Laminin carbohydrates are implicated in cell signaling. AB - We have examined how laminin carbohydrates participate in cellular responses and have focused upon cell spreading and neurite outgrowth. Our earlier studies showed that unglycosylated laminin fully supported cell adhesion but did not promote subsequent spreading of mouse melanoma cells or neurite outgrowth of rat pheochromocytoma cells (Dean et al. (1990): J Biol Chem 265:12553-12562). In the present experiments, we determined whether those cellular responses could be restored to adherent cells. When a mixture of unglycosylated and glycosylated laminins was used as a substratum for mouse melanoma cells, some cells began to spread when 30% glycosylated laminin was present. At least 65% glycosylated laminin was required to elicit a maximal spreading response by the majority of the cells. In separate experiments, we found that cell spreading was fully restored by a pronase digest of glycosylated laminin; a similar digest of unglycosylated laminin had no effect. These results indicate that laminin carbohydrates, rather than polypeptide sequences, were responsible for cell spreading. We also conclude that substrate attachment of the carbohydrate moieties was not essential. In other experiments, laminins containing immature oligosaccharides were produced using two glycosylation pathway inhibitors, swainsonine or castanospermine. When such laminins were used to study cell spreading or neurite outgrowth, laminin containing immature oligosaccharides was as effective as laminin which contains fully processed oligosaccharides. In contrast, laminin with partially processed oligosaccharides had incomplete activity. These composite reconstitution experiments show that laminin carbohydrates provide essential information to responsive cells, enabling them to progress from an adherent state to a spread form or to extend neurite processes. PMID- 1918178 TI - Evidence of an EGF/TGE-alpha--independent pathway for estrogen-regulated cell proliferation. AB - To elucidate the relationship between epidermal growth factor (EGF)/transforming growth factor (TGF-alpha) and estradiol-17 beta (E) in cell proliferation, we examined their effects on the breast cancer cell line, CAMA-1. While E was able to consistently induce cell proliferation under a variety of experimental conditions, EGF/TGF-alpha was without effect. Despite the presence of the receptor (EGFR) gene, mature EGFR protein and mRNA were not detected by radioreceptor assay, 35S Met-labelling, and the Intron Differential RNA/PCR method under conditions in which cells remain responsive to E. Furthermore, TGF alpha is not an autocrine factor in CAMA-1 cells. We demonstrated unequivocally that EGF/TGF-alpha interaction with EGFR is not an obligatory event in mediating estrogen-stimulated cell proliferation. PMID- 1918180 TI - Chronic pain. PMID- 1918179 TI - Constitutive production of lymphocyte activating factors by normal tissues in the adult rat. AB - Lymphocyte activating factors (LAFs), e.g., interleukin-1 (IL-1) and IL-1-like factors, have previously been demonstrated outside the immune system in the skin, thymus epithelium, and the human and rat testis. We have studied the presence of LAFs in normal tissues of the adult rat, utilizing a highly IL-1 sensitive murine thymocyte proliferation assay. We have demonstrated high amounts of LAF activity in the tongue, esophagus, proventricular part of the stomach, and the liver. Some activity was also demonstrated in the duodenum, placenta, spleen, Peyer's patches, glandular stomach, and jejunum, but no bioactivity was present in other gastrointestinal, endocrine, lymphoid, or haematopoeitic tissues. We were also unable to detect any LAF activity in the reproductive organs (except for the testis), urinary tract, skeletal and muscular tissues, brain, eyes, salivary glands, or lung. In the esophagus the activity was mainly localized to the mucosa. The LAF activity in the skin was partly inhibited by treatment with a mixture of antibodies against human IL-1 alpha and IL-1 beta. Dose response curves and gel filtration on a Sephacryl S-200 column suggested the presence of a high molecular weight (90,000-100,000 Da) LAF inhibitory factor in the liver. In all positive tissues, the demonstrated LAFs had a molecular weight of 15,000 25,000 Da, as determined by Sephacryl S-200 gel filtration. Of the positive tissues, the skin, tongue, esophagus, and the proventricular part of the stomach all contain stratified squamous epithelium. It is tempting to suggest that the detected LAFs have a similar function in these barrier tissues, e.g., to serve as host defence factors, or, alternatively or additionally, as tissue growth factors. PMID- 1918181 TI - The use of narcotic analgesics in chronic nonmalignant pain. PMID- 1918182 TI - Literature review of nonpharmacologic methods for the treatment of chronic pain. PMID- 1918183 TI - Application of nonpharmacologic methods of managing chronic pain. PMID- 1918184 TI - A new view of the chronic pain client. PMID- 1918185 TI - Assessment and management of pain in the home care setting: application of Rogers' science of unitary human beings. PMID- 1918186 TI - Pain and promise of aging America. PMID- 1918187 TI - Behavioral management of chronic pain. PMID- 1918188 TI - Helplessness and powerlessness: caring for clients in pain. PMID- 1918189 TI - The impact of chronic pain on the spouse: research and clinical implications. PMID- 1918190 TI - Cancer genetics and the human genome. AB - We can fully expect that the information from the genome project, combined with epidemiologic and other genetic studies, will pinpoint the series of events, in germ cells and somatic cells, that result in the initiation and progression of the various cancers. Within 10 years, the treatment and prevention of at least one of the major common cancers should be within reach. PMID- 1918191 TI - Localization of the early-onset breast cancer gene. AB - In several susceptible families, it is clear that breast cancer is associated with a gene on band q21 of chromosome 17. On the basis of analogy, it seems probable that the rare germ-line gene is prototypical of a mutant form of a gene involved in the pathogenesis of the most common cancer in women. A major effort is now under way to sequence and clone this intriguing gene. PMID- 1918193 TI - The Human Genome Project and clinical medicine. PMID- 1918192 TI - Physician-laboratory interface in X-chromosome mapping. AB - At the world's largest DNA diagnostic laboratory, roughly half of family studies to date have involved X-linked diseases. With the recent characterization of the fragile X gene, that percentage may increase. No matter what the genetic disease, patient studies can be readily combined with physician education, and heightened physician awareness increases the number of referrals. PMID- 1918194 TI - Why yeast? AB - Yeast is an apparently strange "model" for the human genome, but it works because of the high degree of conservation in evolution between the primitive eukaryote and mammals. Moreover, the genic concentration in yeast--with almost no noncoding introns--packs the entire yeast genome into 16 chromosomes with only 10% of the DNA of one human chromosome. PMID- 1918195 TI - DNA sequencing, today and tomorrow. AB - When we have the completed sequence, by about the year 2000, it will be possible to search more efficiently for genes involved in multifactorial diseases, including various cancers. With the genome sequenced and the full complement of genes identified, basic questions about our common biology will become central issues in the twenty-first century. PMID- 1918196 TI - Hypoglycemia in an elderly woman. PMID- 1918197 TI - Tuberculosis: a disease of the 1990s. AB - In the United States, the decades preceding the 1980s were characterized by a decline in the incidence of tuberculosis. More recently, the trend has undergone a significant reversal: Case rates have been increasing by 3% to 6% annually. In 1990, more than 25,700 cases were reported to the Centers for Disease Control. In a sense, tuberculosis is adapting to the '90s. The recent increase in its incidence tends to affect populations with identifiable characteristics. Among the most important of these groups are the populations at high risk for infection by the human immunodeficiency virus. The increase is also fueled by cases in populations that are medically underserved, including foreign-born persons from high-prevalence countries, persons with low incomes, and persons living in long term-care facilities--especially persons with previous tuberculosis infection. Thus, factors such as homelessness, chronic alcohol or drug abuse, malnutrition, and crowded living conditions continue to favor development and transmission of disease. The increase in the incidence of tuberculosis appears to be greatest when subpopulations in such circumstances are also at high risk for HIV infection. Complex issues in the diagnosis and treatment of tuberculosis arise from these epidemiologic patterns. HIV infection is associated with unusual presentations of tuberculosis. Thus, the clinician must maintain a high index of suspicion for the disease in the setting of HIV infection or risk of the infection. The populations at greatest risk are likely to be mistrustful of the medical system, making the long-term administration of potentially toxic chemotherapy more difficult than it already is. Chronic substance abuse may complicate compliance and add further difficulties to the monitoring of chemotherapy. At the same time, the monitoring becomes even more important in the physician's effort to minimize adverse effects of the medications. Outbreaks of drug-resistant disease have recently occurred, complicating the selection of drugs and affecting the duration of treatment. Despite all of these problems, it is essential to establish a diagnosis and initiate treatment rapidly, both to arrest the disease process and to limit its transmission. Since Mycobacterium tuberculosis is spread to uninfected persons in aerosols generated by coughing or sneezing, the infectiousness of a patient with active disease can be related, at least in part, to the number of organisms seen on sputum smears. Initiation of therapy is followed by a rapid decline in infectivity. PMID- 1918199 TI - Neurotic dependence--familial roots. PMID- 1918198 TI - On drug legalization. PMID- 1918200 TI - A young boy with a limp. PMID- 1918201 TI - Mercury finally 'makes it'. PMID- 1918202 TI - Expertise. PMID- 1918203 TI - International health and a changing human ecology. PMID- 1918204 TI - Reversible complete heart block. PMID- 1918205 TI - Evaluation of sexual dysfunction in women. PMID- 1918206 TI - Type I or type II block? PMID- 1918208 TI - Genomic mapping and how it has progressed. AB - Genomic mapping is proceeding at such a rapid pace that any printed version of the anatomy of the human genome is immediately obsolete. Although most of the scientific advances underlying the current explosion in genomic mapping have taken place in the past decade, technologic and methodologic breakthroughs since the 1950s have contributed to the mapping revolution. PMID- 1918207 TI - The human genome initiative: a statement of need. AB - We may never have a complete understanding of the complex dynamics of the human organism, but we can and should know all our genes and begin to understand their role in the diseases that diminish our lives. A 15-year program has been projected and the specific, quantifiable goals in mapping and sequencing are outlined. Ethical, legal, and social implications are also discussed. PMID- 1918209 TI - Identification of disease genes: recent successes. AB - As we continue to localize, sequence, and characterize more and more genes and as we increase our understanding of the biologic function of the gene products--and the nature of the disruptions that mutations can cause--we will come closer to the goals of diagnosis, prevention, and therapy. Progress in the field is proceeding at a pace that no one could have envisioned a decade ago. PMID- 1918210 TI - Use of third-generation cephalosporins. Anaerobes. AB - The third-generation cephalosporins have an increased spectrum of activity against gram-negative bacteria, moderate activity against anaerobic bacteria, and reduced anti-gram-positive activity as compared with earlier cephalosporins. This spectrum allows the drugs to be considered as monotherapy for the treatment of mixed aerobic-anaerobic infections and as prophylaxis in patients in whom such mixed flora are expected. In vitro testing of anaerobes with the third-generation cephalosporins shows susceptibility to be method dependent, with regional differences also observed. The microtube broth dilution method shows the best relationship to in vivo results. Moreover, the apparent in vitro susceptibility or resistance does not always correlate with clinical efficacy. Clinical studies indicate that the expanded-spectrum third-generation cephalosporins may be used in place of combination therapy in patients with polymicrobial infection or as prophylaxis when mixed microflora are expected. PMID- 1918211 TI - Use of third-generation cephalosporins. Pseudomonas. AB - Although the frequency of infection with P. aeruginosa has declined in many centers treating neutropenic patients with cancer, infections still occur and can be accompanied by considerable morbidity and mortality. Furthermore, patterns of infection can change again, and Pseudomonas may reemerge. Thus, in high-risk, immunocompromised patients, adequate bacterial coverage for P. aeruginosa should be part of any empiric regimen. Third-generation cephalosporins are an important part of the therapeutic armamentarium for the empiric management of neutropenic patients. Assuming a low level of resistance at a given center, however, only ceftazidime and cefoperazone possess sufficient antipseudomonal activity to be used for monotherapy. If other third-generation cephalosporins are used, it is imperative that an aminoglycoside or an antipseudomonal penicillin be added. But even when combined with an aminoglycoside, ceftriaxone would not be a good choice for neutropenic patients. It is an important agent in non-neutropenic hosts or in other immunocompromised patients in whom infection with Pseudomonas is unlikely to occur. PMID- 1918212 TI - Use of third-generation cephalosporins. Hemophilus influenzae. AB - Meningitis constitutes the major infection associated with H. influenzae. Caution must be used when selecting antibiotic treatment based on MIC data, alone, because bacterial levels in the cerebrospinal fluid are higher than those in the blood, on which MICs are calculated. Certain third-generation cephalosporins are effective in producing maximum killing of H. influenzae in the CSF. This strong bactericidal activity may actually prove to be detrimental, however, by augmenting the inflammatory response, and thus contributing to the complications and the sequelae of meningitis. The addition of an agent to block the exaggerated response may be possible. PMID- 1918213 TI - Use of third-generation cephalosporins. Enterobacteriaceae. AB - Enterobacteriaceae are ubiquitous pathogens that cause community-acquired and nosocomial infections at many sites. Third-generation cephalosporins and monobactams are generally the parenteral drugs of choice for the non-beta lactamase-producing Enterobacteriaceae, with ceftriaxone usually preferred because it is equally effective to the others and can be given once a day. They are also good alternative drugs for patients with Salmonella infections who fail to respond to or cannot tolerate ampicillin or trimethoprim-sulfamethoxazole. PMID- 1918214 TI - Use of third-generation cephalosporins. Spirochetes. AB - Although dosing schedules are still being worked out, ceftriaxone has been shown to be effective in both primary and secondary syphilis. In our experience, ceftriaxone was the drug of choice for the treatment of Lyme disease. PMID- 1918215 TI - Use of third-generation cephalosporins. Staphylococci. AB - A large percentage of S. aureus infections occur by autoinoculation of the organism associated with persistent nasal carriage. Thus, newer modalities to interrupt nasal carriage may be useful in decreasing hospital-acquired S. aureus infections. The combination of a first-or, in some cases, a third-generation cephalosporin with an aminoglycoside is highly effective empiric treatment of putative infections due to S. aureus. And, the third-generation cephalosporins appear to be effective alone against beta-lactam antibiotic-sensitive staphylococci. For example, ceftriaxone has excellent inhibitory and bactericidal concentrations against these organisms and because of its superior pharmacokinetic properties is an indicated option for long-term treatment of defined beta-lactam antibiotic-sensitive S. aureus infections. PMID- 1918216 TI - Use of third-generation cephalosporins. Streptococci. AB - The third-generation cephalosporins are highly active against nonenterococcal streptococci. The subgroup of ceftizoxime, ceftriaxone, and cefotaxime are similar to penicillin in their activities by weight; and the drug with the longest half-life, ceftriaxone, offers the potential for home therapy for selected patients with endocarditis. PMID- 1918217 TI - Ceftriaxone in treatment of serious infections. Meningitis. AB - In many pediatric infectious disease programs, ceftriaxone or cefotaxime is now the preferred drug for bacterial meningitis caused by H. influenzae, meningococci, and pneumococci. Ceftriaxone reaches a high bactericidal titer in the cerebrospinal fluid and persists at the site of infection longer than any other beta-lactam antibiotic. Short-course, once-daily therapy with ceftriaxone requires more study; currently, many pediatricians administer the agent twice daily for suspected or proven meningitis. Given the association of sequelae with prolongation of positive CSF cultures, ceftriaxone's rapid bactericidal activity is an advantage, which may require an adjunctive agent to block the inflammatory response due to antibiotic-induced release of endotoxin and other cell wall components. As empiric therapy, ceftriaxone is effective in infants and children three months to 18 years old. It is not yet recommended in neonates, because of concerns about bilirubin displacement. Thus, infants up to three months of age should receive ampicillin plus cefotaxime. In adults, ceftriaxone is effective therapy for presumed bacterial meningitis but must be combined with ampicillin initially, since L. monocytogenes meningitis cannot be excluded in most cases until CSF culture results are available. PMID- 1918218 TI - Ceftriaxone in treatment of serious infections. Sexually transmitted diseases. AB - The most recent CDC guidelines for treatment of STDs list a number of syndromes for which ceftriaxone is the recommended therapy, including those caused by N. gonorrhoeae and H. ducreyi. The drug has successfully eradicated incubating syphilis. Its use in primary, secondary, and latent syphilis is promising, although adequate data regarding optimal dose and duration of therapy are not yet available. It remains to be seen whether ceftriaxone represents the sun rising on a new era of successful STD treatment or the sun setting on the old penicillin era. PMID- 1918219 TI - Ceftriaxone in treatment of serious infections. Skin and soft tissue infections. AB - Ceftriaxone is generally recognized to be safe and effective when administered either intravenously or intramuscularly to both adults and children as a single drug for skin and skin structure infections. An advantage of ceftriaxone over the other third-generation cephalosporins is its long serum half-life, which allows it to be given every 12 hours in children and every 24 hours in most adults. There is no question that ceftriaxone is effective for skin and soft tissue infections, particularly those caused by staphylococci and streptococci. The drug's sales to home infusion companies around the country attest to its widespread use for such infections. The fact remains, however, that the data required to substantiate efficacy and safety for ceftriaxone or for any of the other third-generation cephalosporins are just not available in large numbers. PMID- 1918220 TI - Ceftriaxone in treatment of serious infections. Osteomyelitis. AB - Ceftriaxone is an effective and safe agent for the treatment of osteomyelitis. It is active against most of the causative organisms. Combined with surgery, it is useful for all types of osteomyelitis. In addition, its once-daily dosing has made outpatient therapy feasible for most patients. Questions that remain are whether full treatment with 2 gm every 24 hours for four to six weeks is needed for osteomyelitis or whether 1 gm/day would provide comparable results. The relevance of minimal inhibitory/bactericidal concentrations and serum inhibitory/bactericidal concentrations has not been-determined. Some questions remain about the cure rate of ceftriaxone against S. aureus osteomyelitis, although most cases do well. Comparative studies with agents such as cefazolin or oxacillin would be helpful to resolve this issue. Long-term follow-up of patients treated for osteomyelitis outcome has not been done in sufficient detail to be certain of the comparative results of different antimicrobials. The success rate of the quinolones against gram-negative osteomyelitis appears good, but their activity against gram-positive organisms is uncertain, and development of resistance is a problem. Questions still linger in regard to how much can be accomplished with antimicrobial therapy without surgery and how long antimicrobials are needed once effective surgery has been performed. PMID- 1918221 TI - Ceftriaxone in treatment of serious infections. Pneumonia and lower respiratory tract infections. AB - One gram once daily of ceftriaxone is as effective as 2 gm for the common causative organisms of community-acquired and nosocomial pneumonias. It should not be used alone against L. pneumophila, the TWAR pneumoniae, and possibly anaerobic pathogens. Preliminary study suggests that a regimen of 500 mg a day may be effective in selected patients with simple pneumonias caused by sensitive pathogens. Ceftriaxone is safe, well tolerated, and cost-effective, which means it can play a significant therapeutic role in nursing homes and other long-term care facilities as well as in outpatient therapy. PMID- 1918222 TI - Ceftriaxone in treatment of serious infections. Septicemia. AB - Ceftriaxone is generally recognized as safe and effective when used as a single drug in the therapy of septicemia and other serious infections involving bacteremia in both adults and children. An advantage of ceftriaxone over other third-generation cephalosporins is its long serum half-life, which allows the drug to be given every 12 hours in children or less frequently in adults. PMID- 1918223 TI - Ceftriaxone in treatment of serious infections. Urinary tract infections. AB - Ceftriaxone is active against many gram-negative bacillary uropathogens. It achieves very high levels in urine and proximate tissue following single daily doses. Clinical and bacteriologic results in infections due to susceptible organisms have been excellent. Additional comparative studies with longer follow up may assist in further delineating the relative role of ceftriaxone in management of infections of the urinary tract. PMID- 1918224 TI - Pharmacokinetics of ceftriaxone. AB - Ceftriaxone fulfills many of the qualities of an ideal antibiotic: a prolonged elimination half-life, which results from a "restrictive" excretion pattern; saturable protein binding, which provides the theoretical basis for administering the total daily dose as a single bolus; and once-a-day dosing, which provides plasma and tissue concentrations that exceed the MIC for most susceptible pathogens for 24 hours. PMID- 1918225 TI - Intercountry adoption: a review of the evidence. AB - Studies of the outcome of intercountry adoption are reviewed in the context of its history and politics. Intercountry adoption is a post-World War II phenomenon, and has become largely a service for childless couples in the West. Many Third World countries, and some Western social workers, are bitterly opposed to the practice, on both political and psychological grounds. Outcome studies have produced results similar to those found in studies of incountry adoption, although, to date, insufficient attention has been paid to issues of identity and racism. The policy implications of these studies will depend on political considerations, as well as the research evidence. PMID- 1918227 TI - The use of intonation to communicate in pervasive developmental disorders. AB - The objective of this paper was to employ a functional linguistic approach to explore pragmatic failure in the spontaneous speech of subjects with pervasive developmental disorders (PDD). Patterns of intonation use were compared among subjects with Asperger's syndrome (AS), high-functioning autism (HFA), and psychiatric out-patient controls (OPC) with a variety of non-specific social problems. Written transcripts and audio-recordings were used to measure rates of various intonation types relative to the amount of speech produced. The major finding of the study was that the HFA subjects less often tend to employ useful patterns of intonation for communication than the AS or OPC groups. This suggests that HFA either send random intonation signals to hearers or else demonstrate systematic misuse of the linguistic system. AS subjects differed little from the controls. The implications of these results for understanding the communicative failure of PDD subjects is discussed. PMID- 1918226 TI - Determinants of expressed emotion in families of disturbed and normal children. AB - Both high expressed emotion (EE) and psychiatric disorders were frequent in the parents of children and adolescents with disruptive behavior disorder (DBD, N = 34) and obsessive compulsive disorder (OCD, N = 49) compared to normal controls (NC, N = 41). Parental psychiatric diagnosis was significantly related to high-EE in fathers (p = .0002) and mothers (p = .0001) of all groups combined, and in parents of the ill groups (p = .03). Absence of diagnosis was associated with low EE in fathers (p = .0006) and mothers (p = .04) of the controls. Psychiatric diagnosis was the only significant predictor for high-EE in fathers, while for mothers child's diagnosis was a stronger predictor. PMID- 1918228 TI - Differential prediction of young adult arrests for property and personal crimes: findings of a cohort follow-up study of violent boys from North Carolina's Willie M Program. AB - Which characteristics of violent youth predict adult arrest for property crimes (e.g. burglary), and for personal crimes (e.g. assault)? We addressed this question by focusing on a group of particularly violent and assaultive boys. Separate logistic regression analyses were conducted to predict property and personal crime arrests as a function of adolescent psychiatric diagnosis, behavior problem history, race and IQ. Property crime arrest was predicted by an adolescent history of property offenses, conduct disorder diagnosis, and race (more arrests among non-whites than whites). Personal crime arrest was predicted by adolescent history of property offenses and adolescent history of substance abuse. PMID- 1918229 TI - Marital disharmony and children's behaviour problems: aspects of a poor marriage that affect children adversely. AB - The aim of this study was to investigate the elements of the parental marital relationship which put children at risk for behavioural and emotional problems. Data from 119 families from the general population with a child aged between 9 and 12 years were analysed for the present study. The relationship between children's emotional and behavioural problems and overt parental conflict, covert tension between parents and discrepancy on child-rearing practices was assessed. Overt parental conflict was found to relate most strongly to children's emotional and behavioural problems using mothers', fathers' and children's accounts of the children's symptoms and after controlling for other aspects of marital disharmony. Aspects of the parent-child relationship were hypothesized as mediating variables in the relationship between parental conflict and children's emotional and behavioural problems, but the data did not support this hypothesis. PMID- 1918231 TI - Somatic complaints and their relationship to depressive symptoms in Swedish adolescents. AB - This study investigated the prevalence of somatic complaints among Swedish adolescents aged 13-18 years. Assessment was made by means of questionnaires given to normal boy and girl students in a school sample, but in headache, headache-free, and psychiatric inpatient groups were restricted to girls only. Furthermore, the relationship between somatic and depressive symptoms was examined. In agreement with previous research, the results indicated that normal girls consistently have more frequent and severe somatic complaints. In this sample, the frequency of self-reported symptoms was highest among 13 year olds. For the majority of somatic items, adolescents in the psychiatric group reported more frequent and severe symptoms than those in the contrast conditions. Although significant correlations between total somatic and depressive symptoms were obtained, the power of the most potent somatic items to discriminate between a depressive and nondepressive state among adolescents was weak. PMID- 1918230 TI - Life events, depression, and perceived problem solving alternatives in adolescents. AB - The association between negative life events and depression may be mediated by adolescents' sense of competency in solving problems. This study investigated (a) the relationship between troublesome life events and level of depression and (b) the association between level of depression and adolescents' perceived problem solving alternatives, in 135 tenth graders. The specific life events of "unemployment of a family member", "starting at a new school", and "breaking up with a boy/girlfriend", were associated with higher levels of depression. In addition, higher levels of depression were associated most consistently with the perceived alternatives of getting intoxicated and of isolating oneself in response to a variety of problems. Further research is needed to clarify both the extent to which depression influences adolescents' responses to negative life events and leads to poorer problem solving choices, and the degree to which negative life events and the lack of constructive problem solving alternatives increase the risk of depression. PMID- 1918232 TI - Clinic observations in the assessment of pervasiveness of childhood hyperactivity. AB - Sixty-one boys, 6-12 years old, met both the diagnostic criteria of ADHD of DSM III-R and hyperkinetic syndrome of ICD-9. They could be subdivided into two groups: 43 showed hyperactive symptoms in the clinic situation and 18 did not. The former group were younger and showed significantly poorer performance in measures of general intelligence, attention, cognitive styles, motor clumsiness and minor neurological deficits. Controlling for age and intelligence attenuated the differences, but significant differences remained in activity level, attention, and minor neurological deficits. This result suggests that direct observation is important in the assessment of pervasiveness of childhood hyperactivity. PMID- 1918234 TI - Clinical note: childhood neurotic disorders with a sexual content need not imply child sexual abuse. AB - Two cases are described of childhood obsessional states in which the content of the symptomatology led parents and professionals to suspect child sexual abuse. Following assessment it was felt, on the balance of probabilities, unlikely that child sexual abuse had occurred in either case. Both children had previously engaged in "sex play" with peers. Maternal attitudes to sexuality were felt to have influenced their daughters' views about sexual behaviour and to have contributed to the children's guilt feelings. Response to appropriate treatment was rapid and has been sustained in the short-term. The importance of avoiding lengthy and possibly damaging assessment procedures in such cases is discussed. PMID- 1918233 TI - Psychological disturbance and its associations in the children of the Gujarati community. AB - The infrequent referral of Asian children to child psychiatry clinics was noted. By administering Rutter's scale A2 to samples of Gujarati and English parents with children between the ages of 4 and 7 years a lower rate of disturbance was demonstrated among the Asian sample providing an explanation for the original observation. Family and child-rearing factors associated with disturbance were identified. PMID- 1918235 TI - Determination of vanilmandelic acid in urine by coupled-column liquid chromatography combining affinity to boronate and separation by anion exchange. AB - An automated liquid chromatographic method for assaying vanilmandelic acid in urine is described. Vanilmandelic acid and potential interfering substances, such as catechol compounds and their metabolites, have been tested for affinity to boronic acid-substituted silica at various pH values. Vanilmandelic acid and the internal standard, isovanilmandelic acid, were bound to the boronate matrix at an acidic pH, whereas for instance catecholamines were unretained and passed through the column. The alpha-hydroxycarboxylic acids were then desorbed by another mobile phase (pH 6.0) and transferred to an anion exchanger for chromatography and electrochemical detection. A relative standard deviation of 2.8% was obtained for the analysis of human urine samples containing 6.6 microM vanilmandelic acid. PMID- 1918236 TI - Gas chromatographic-mass spectrometric determination of two new antimycotic agents, 1-[(5-chloro-2-benzofuranyl)(2-chlorophenyl)methyl]-1H-imidazole and 1 [(5-bromo-2-benzofuranyl)phenylmethyl]-1H-imidazole, in rabbit plasma following topical administration: a preliminary comparison with bifonazole. AB - A method for the analysis of the antimycotic drugs 1-[(5-chloro-2-benzofuranyl)(2 chlorophenyl)methyl]-1H-imidazole, 1-[(5-bromo-2-benzofuranyl)phenylmethyl]-1H imidazole and bifonazole in rabbit plasma, employing gas chromatography-mass spectrometry with selected-ion monitoring, was developed. The procedure involved single-step purification of the biological matrix via liquid-liquid extraction on Extrelut columns and use of a carrier substance to minimize the negative effects of adsorption sites during the gas chromatographic process. The limits of detection ranged from 0.1 to 1.4 ng/ml, starting from a 200-microliter sample. The method was applied to a preliminary evaluation of percutaneous absorption of both drugs in the rabbit after a single administration, in comparison with bifonazole. PMID- 1918237 TI - New analyser for the determination of urinary vanillylmandelic acid, homovanillic acid and creatinine. AB - We have developed a novel analyser for the determination of vanillylmandelic acid, homovanillic acid and creatinine in urine by high-performance liquid chromatography using three different types of column, cation-exchange, anion exchange and reversed-phase and the column-switching technique. In this procedure, 10 microliters of intact urine were directly injected into the cation exchange column, and the pass-through fraction, containing vanillylmandelic acid and homovanillic acid was transferred to the anion-exchange column by column switching. The fraction partially purified from endogenous urinary impurities on the anion-exchange column was transferred to the reversed-phase column. Vanillylmandelic acid and homovanillic acid, separated by the solvent-switching technique, were detected fluorimetrically (excitation at 280 nm, emission at 320 nm). Then, creatinine eluted from the cation-exchange column is spectrophotometrically detected (254 nm). Therefore the successive simultaneous analysis of the three could be performed in a 15-min cycle; the within-assay coefficients of variation for normal and patients' urines were less than 1.9%, less than 3.3% and less than 3.0% for vanillylmandelic acid, homovanillic acid and creatinine, respectively; the recoveries averaged 100, 103 and 100%, respectively, for supplemented urines. PMID- 1918238 TI - Determination of sultopride and tiapride in serum by gas chromatography using a surface ionisation detector. AB - A sensitive and selective method has been developed for the determination of sultopride and tiapride in serum using gas chromatography with a surface ionisation detector. No interfering peaks from endogenous substances were observed. The method showed good reproducibility and accuracy, and the standard curve was linear up to 2 micrograms/ml with a correlation coefficient of 0.999. This method is applicable to pharmacokinetic studies and therapeutic drug monitoring of sultopride and tiapride. PMID- 1918239 TI - Determination of ampicillin in biological fluids by coupled-column liquid chromatography and post-column derivatization. AB - A rapid and sensitive high-performance liquid chromatographic method has been developed for the determination of ampicillin in plasma and urine. The method involves a simple deproteinization step and separation on a coupled-column chromatographic system followed by post-column derivatization and fluorescence detection. The method has been used for the determination of ampicillin in various clinical studies. The high sensitivity makes it especially useful for small sample volumes, e.g. samples from pediatric patients. PMID- 1918240 TI - High-performance liquid chromatographic determination of loracarbef, a potential metabolite, cefaclor and cephalexin in human plasma, serum and urine. AB - A high-performance liquid chromatographic (HPLC) method is reported for the determination of a new carbacephem antibiotic, loracarbef, a hydroxylated analogue, and two cephalosporins, cefaclor and cephalexin, in plasma, serum, and urine. The antibiotics are extracted from plasma by means of C18 solid-phase cartridges. Urine samples are diluted with water and directly injected on the HPLC system. The HPLC system utilizes a Supelcosil LC-18-DB (250 mm x 4.6 mm I.D.) reversed-phase column and ultraviolet detection at 265 nm. The limit of quantitation is 0.5 micrograms/ml for each compound. Excellent correlation of plasma concentrations is shown between results determined by HPLC and those obtained by microbiological agar-well diffusion assays. Stability studies of loracarbef in human plasma show the antibiotic to be stable for at least 24 h at room temperature and for at least twelve months at -20 degrees C. PMID- 1918241 TI - Determination of atropine in biological specimens by high-performance liquid chromatography. AB - A sensitive and selective method for the determination of atropine in biological specimens has been developed. Samples alkalinized with sodium hydroxide were extracted with dichloromethane, and the organic phase was evaporated in a water bath at 50 degrees C for ca. 10 min. The residue was dissolved in the mobile phase and injected into a reversed-phase column (TSK gel ODS-120A). The retention time for atropine could be varied by changing either the acetonitrile-water ratio in the mobile phase or the pH of the mobile phase. Acetonitrile-water (2:8, v/v) containing 6 mM phosphoric acid was used as mobile phase. Samples of 200 microliters or less were injected into the chromatography and measured at 215 nm. The recoveries of atropine added to drug-free specimens were satisfactory with coefficients of variation of 4% or less. Ninety-two compounds tested did not interfere with the assay of atropine. The method has been applied for monitoring atropine concentrations in cases of organophosphate and drug poisoning. PMID- 1918242 TI - Selective high-performance liquid chromatographic method for the determination of glycyrrhizin and glycyrrhetic acid-3-O-glucuronide in biological fluids: application of ion-pair extraction and fluorescence labelling agent. AB - A selective high-performance liquid chromatographic method has been developed for the simultaneous determination of glycyrrhizin and glycyrrhetic acid-3-O glucuronide in biological fluids of the rat. The procedure is based on the ion pair formation using tetra-n-amylammonium bromide, extraction with ethyl acetate n-heptane from the salt-saturated aqueous phase, labelling with 4-bromomethyl-7 methoxycoumarin, followed by chromatographic separation with fluorescence detection. Glycyrrhizin in plasma, bile and urine could be precisely determined in concentrations as low as 1, 1 and 2.5 micrograms/ml, respectively, in a 0.1-ml sample. The equivalent values for the glucuronide were 1, 2.5 and 2.5 micrograms/ml, respectively. The method is applicable in pharmacokinetic studies of glycyrrhizin in small animals. PMID- 1918243 TI - Comparative study on the determination of the anti-neoplastic drug teniposide in plasma using micellar liquid chromatography and surfactant-mediated plasma clean up. AB - The potential of micellar liquid chromatography and of an on-line surfactant mediated sample cleanup, which involves column-switching prior to conventional reversed-phase high-performance liquid chromatography, has been evaluated for the determination of the anti-neoplastic drug teniposide in plasma by using electrochemical detection. A major advantage of surfactant-mediated techniques is that they allow fully automated processing of plasma samples, because protein precipitation is prevented by the addition of the surfactant sodium dodecylsulphate. With the automated column-switching technique, a degree of sample enrichment and of selectivity can be attained, which is similar to that for the conventional procedure which, however, involves a labour-intensive off line isolation of teniposide, using liquid-liquid extraction prior to chromatography. An inherent drawback of automated micellar liquid chromatography is that no sample clean-up or preconcentration can be carried out, which results in only a moderate detection limit and selectivity. The linearity, reproducibility and recovery of the surfactant-mediated techniques are similar to those of the conventional procedure. Based on the presented results, it was concluded that the surfactant-mediated column-switching technique is a highly attractive sample enrichment technique with respect to simplicity, speed and cost. PMID- 1918244 TI - Bioanalysis of diclofenac as its fluorescent carbazole acetic acid derivative by a post-column photoderivatization high-performance liquid chromatographic method. AB - A sensitive and selective bioanalytical liquid chromatographic method for diclofenac is described. The drug was detected as a flourescent derivative, which was demonstrated by 1H NMR and mass spectrometric studies to be carbazole acetic acid. Diclofenac was derivatized by UV irradiation of the substance performed as a post-column photoreaction. The reactor was a PTFE capillary wound around a 254 nm UV lamp. Diclofenac was isolated from the plasma samples by precipitation of the proteins with acetonitrile. A 50-microliters volume of the supernatant was injected onto a Nucleosil C18 column. The mobile phase was 32% acetonitrile in pH 6.6 buffer. Carbazole acetic acid was detected by a fluorescence detector using an excitation wavelength of 288 nm and an emission wavelength of 360 nm. The recovery was 92%, the standard curve was linear in the range 10-5500 ng diclofenac per ml plasma, and the relative standard deviation at 10 and 5000 ng of diclofenac per ml plasma was 9.0% and 3.3%, respectively. The limit of detection was 6 ng/ml at an injection volume of 50 microliters. Chromatograms of human and rat plasma containing diclofenac are shown. PMID- 1918245 TI - On-line solid-phase extraction of piroxicam prior to its determination by high performance liquid chromatography. AB - A direct method for the determination of piroxicam in plasma is described. Plasma is directly injected onto the extraction column (10 mm x 2 mm I.D., packed with 40-microns Bond Elut C2) where proxicam is separated from the plasma concomitants using a solid-phase extraction procedure. Using a laboratory-made on-line column switching system, the drug is quantitatively transferred and separated on the analytical column (15 cm x 4.6 mm I.D., Supelcosil LC18 DB, 5 microns) followed by determination using ultraviolet absorption at 331 nm. Validation of the method demonstrated a good recovery (100%), sensitivity (limit of determination 0.2 microgram/ml, based on a 20-microliters sample volume), accuracy and precision (better than 5%). The developed method has been adopted for studying the steady state pharmacokinetics of the drug. PMID- 1918246 TI - Determination of femtomole/milliliter concentrations of enprostil acid in human plasma using high-performance liquid chromatography-laser-induced fluorescence detection. AB - This paper describes the use of multiple-column high-performance liquid chromatography (HPLC) combined with laser-induced fluorescence for the determination of femtomole/milliliter concentrations of enprostil acid, a prostaglandin analogue, in human plasma. The drug is isolated from plasma by phenyl solid-phase extraction and fluorescently labeled at its carboxyl functional group with a large excess of 2-bromoacetyl-6-methoxynaphthalene. A multi-column method using both normal- and reversed-phase chromatography is necessary to separate the labeled drug from the unreacted reagent. Post-column dilution of the mobile phase with water after the reversed-phase chromatography allows on-line concentration of the labeled analyte onto a guard column prior to the microbore HPLC. A loop guard column device provides a simple way to inject up to 1.0 ml of sample solution onto a microbore column without significantly reducing the column efficiency. A 325-nm He-Cd laser is used to excite the labeled drug, and fluorescence emission is monitored at 450 nm. Using this system, we are able to derivatize, detect, and quantify 5 pg of the prostaglandin analogue in 1.0 ml of plasma. PMID- 1918247 TI - Automated separation and quantitation of lipid fractions by high-performance liquid chromatography and mass detection. AB - This report describes an improved separation and quantitation of lipid fractions in a total lipid extract by high-performance liquid chromatography using a modified solvent and gradient system delivered by dual pumps and incorporating a mass detector and autosampler. The detector responses for various lipid fractions (cholesteryl esters, triacylglycerols, free cholesterol, and seven major phospholipid classes) were fitted to a quadratic equation, y = ax2 + bx + c, and quantified after detector calibration by a computer. This new system has the advantage of automation and reproducible separation. The present method was applied to rat liver analysis. PMID- 1918248 TI - Determination of p-methylthiobenzamide and p-methylthiobenzamide-S-oxide from rat plasma using solid-phase extraction and high-performance liquid chromatography. AB - p-Methylthiobenzamide (PMTB) is a thiocarbonyl compound exhibiting marked hepatotoxicity and nephrotoxicity. We describe a high-performance liquid chromatographic method for analyzing PMTB and a metabolite, p-methylthiobenzamide S-oxide (PMTBSO), from rat plasma using a solid-phase extraction technique. In this way, PMTB and PMTBSO can be extracted from 0.5 ml of plasma and separation achieved by an ODS analytical column in as little as 9 min. The mobile phase used was methanol-water (55:45, v/v) and the wavelength for detection was 290 nm. The limits of detection in plasma were 15 ng/ml for PMTB and 33 ng/ml for PMTBSO; the absolute recovery from spiked plasma samples was greater than 84.4% for both compounds and the internal standard. The method was linear throughout the range used with correlation coefficients greater than 0.969. The intra-day accuracy ranged from 1.52 to 15.23% relative error for the PMTB concentration range 151 3025 ng/ml; accuracy of 4.97% or less was obtained for PMTBSO concentrations of 1672-20,068 ng/ml. The intra-day precision (coefficient of variation) of the procedure was found to be no greater than 5.28% for PMTB and 7.9% for PMTBSO. Inter-day accuracy and precision measurements were similar. PMID- 1918249 TI - Solid-phase extraction and direct high-performance liquid chromatographic determination of metoprolol enantiomers in plasma. AB - A method is described by which underivatized metoprolol enantiomers in plasma can be quantitated by high-performance liquid chromatography with fluorescence detection. Samples are prepared for injection using a simple solid-phase extraction procedure which is essentially 100% efficient for all analytes. The metoprolol enantiomers are resolved using a cellulose tris(3,5 dimethylphenylcarbamate) chiral stationary phase and a hexane-ethanol diethylamine mobile phase. Samples were tested for adaptability to autoinjection and found to be stable for at least 16 h after reconstitution in mobile phase. The automated method was determined to be precise and accurate for enantiomer concentrations as low as 10 ng base per ml and was successfully employed in a pharmacokinetic investigation. PMID- 1918250 TI - Enantioselective determination of dimethindene in urine after oral administration of racemic dimethindene. AB - A sensitive high-performance liquid chromatographic determination of dimethindene and its metabolite N-demethyldimethindene in urine has been developed. The quantitative analysis was followed by determination of the enantiomeric ratio of dimethindene on an alpha 1-AGP column (EnantioPac). The urinary data for nine volunteers after oral administration of racemic dimethindene are presented. The isolation, identification and synthesis of the metabolite N-demethyldimethindene are reported. PMID- 1918251 TI - Measurement of plasma catecholamines by high-performance liquid chromatography with electrochemical detection in intensive care patients after dobutamine infusion. AB - A procedure for the determination of plasma catecholamine concentrations in critical care patients after dobutamine infusion is presented. A modified chromatographic system is required with an additional washing procedure to achieve maximum sensitivity and stable chromatographic conditions. The influence of storage time on the catecholamine concentrations of plasma samples is reported in detail. A time-dependent decrease in catecholamine concentrations of up to 12 and 39% was found within two and ten months, respectively. PMID- 1918252 TI - High-performance liquid chromatographic separation of human apotransferrin and monoferric and diferric transferrins. AB - A simple method for the chromatographic separation of the different molecular forms of human transferrin according to their respective iron contents is described. The appropriate conditions were developed with a Mono-S cation exchange column. PMID- 1918253 TI - High-performance liquid chromatographic determination, with ultraviolet detection, of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine in rat tissues and simultaneously of normetanephrine and metanephrine for phenylethanolamine-N-methyltransferase or catechol-O-methyltransferase activities. AB - A high-performance liquid chromatographic method, with ultraviolet detection, for the determination of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine, and simultaneously of normetanephrine and metanephrine, is presented. The separation was carried out by reversed-phase ion-pair isocratic chromatography. This procedure was applied to the study of the content of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine in rat brain and adrenal glands and to the measurement of phenylethanolamine-N-methyltransferase or catechol-O-methyltransferase activities in rat adrenal gland. PMID- 1918254 TI - Simultaneous assay for isoniazid and hydrazine metabolite in plasma and cerebrospinal fluid in the rabbit. AB - A simple procedure for the simultaneous determination of isoniazid and hydrazine metabolite in plasma and cerebrospinal fluid in the rabbit is described. The assay involves organic extraction before and after derivatization of the two compounds and the internal standard, phenelzine. The extract of the derivatized compounds was evaporated to dryness at 40 degrees C and the residue redissolved in the mobile phase (50 microliters). A 25-microliters aliquot was injected into the liquid chromatograph and eluted with acetonitrile-water-triethylamine (70:30:0.4, v/v) containing 5 mM heptanesulphonic acid on a 30-microns C8 precolumn linked to a 10-microns C18 microBondapak column at ambient temperature (25 +/- 1 degree C). The eluate was detected by ultraviolet detection at 320 nm. PMID- 1918255 TI - Rapid method for preparing a beta-glucan-specific sensitive fraction from Limulus (Tachypleus tridentatus) amebocyte lysate. AB - By separating Limulus amebocyte lysate by cation-exchange chromatography with an SP-Toyopearl 650C column, a fraction insensitive to endotoxin, yet specifically sensitive to beta-glucan, was successfully obtained in the unadsorbed portion. This fraction showed beta-glucan dose-dependent clotting enzyme activity, although no sensitivity to endotoxin. This beta-glucan-dependent reaction showed no interference in the presence of endotoxin, with the fraction also showing sensitivity towards various kinds of beta-glucan, i.e. curdlan, pachyman, laminaran and lichenan. The sensitivity towards curdlan was approximately 10(-10) g/ml. PMID- 1918256 TI - High-performance liquid chromatographic assay of alpha-(4-fluorophenyl)-4-(5 fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY 14802), a potential antipsychotic drug, in monkey and rat plasma. AB - A high-performance liquid chromatographic-fluorescence method was developed for the quantitative analysis of BMY-14802 (I) in monkey and rat plasma. After the addition of the internal standard (BMY-14853 I.S.), 250 microliters of plasma were made basic by the addition of 2 ml of saturated sodium carbonate buffer. Compound I and the I.S. were then extracted into 5 ml of methyl tert.-butyl ether. The organic phase was evaporated and the resulting residue was reconstituted in mobile phase. Final separation and quantitation of I was achieved on an octadecyl column with a 0.05 M potassium phosphate-acetonitrile triethylamine-85% phosphoric acid (650:350:0.1:0.05, v/v) mobile phase. Fluorescence detection was used to monitor the eluent at an excitation wavelength of 240 nm and an emission wavelength of 400 nm. The limit of detection was 0.5 ng/ml. The standard curve was linear over the range 5.0-1000 ng/ml. Intra-assay and inter-assay precision values were less than 4.0% relative standard deviation and accuracy was within 12% of nominal values. Compound I was shown to be stable in monkey and rat plasma for at least six months when stored at -20 degrees C. PMID- 1918257 TI - High-performance liquid chromatographic analysis of trilostane and ketotrilostane in rat plasma. AB - A simple high-performance liquid chromatographic (HPLC) method for assaying trilostane, a synthetic steroid, and one of its metabolites, ketotrilostane, in small volumes of rat plasma has been developed. A single liquid-liquid extraction was used to isolate the two compounds from acidified plasma prior to the quantitative analysis. The HPLC conditions involved the use of a Spherisorb ODS column (250 mm x 4.6 mm I.D.) and a mobile phase of 1,4-dioxan-Sorenson's buffer at pH 5.0 (52:48, v/v). Ethisterone was used as an internal standard. Trilostane and ketotrilostane were detected by their ultraviolet absorbance at 255 nm. Recoveries greater than 80% and detection limits of 50 ng/ml were obtained for both compounds. Inter-day coefficients of variation were less than 10%. PMID- 1918258 TI - Rapid isocratic method for the separation and quantification of major phospholipid classes by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method for the quantification of major phospholipid classes is described. The separation was performed on Ultrasphere SI silica gel columns with a mobile phase of acetonitrile-methanol-85% phosphoric acid (100:10:1.8. v/v) using isocratic elution and UV detection at 203 nm. Complete separation of phosphatidylserine, phosphatidylethanolamine, plasmalogen, phosphatidylcholine and sphingomyelin was achieved within 8 min. The plasmalogen was resolved from phosphatidylethanolamine in hydrochloric acid-derivatized samples, or without derivatization using a mobile phase composition of 100:40:0.4. The phospholipids were quantified by peak-area integration by means of the calibration. The detection limit is 5 ng. Human erythrocyte ghost membranes, lymphocytes and thrombocytes were analysed for these phospholipids. This method is suitable for routine clinical studies of membrane disorders in health, toxicity and disease, as well as in research. PMID- 1918259 TI - Simultaneous analysis of prednisone, prednisolone and their major hydroxylated metabolites in urine by high-performance liquid chromatography. AB - A high-performance liquid chromatographic technique for the simultaneous determination of prednisone, prednisolone and their major hydroxylated metabolites, viz., 20 beta-hydroxyprednisone, 6 beta-, 20 alpha- and 20 beta hydroxyprednisolone, in human urine is presented. The retention times were 6.5, 11.4, 18.1, 24.2, 31.6 and 35.3 min, respectively. The technique employs betamethasone as the internal standard. Samples are extracted with ethyl acetate using a diatomaceous earth extraction column, and the extract was dried and injected onto a silica gel column with ultraviolet detection at 254 nm. The calibration curve is linear within the studied range 50-1500 ng/ml for prednisolone and 50-750 ng ml for the other steroids. The intra-day and inter-day coefficients of variation are less than 10% for prednisone and prednisolone but higher for the metabolites. The assay was used to study the excretion rate profile of each of these steroids in the urine of a normal male subject receiving a 49.3-mg intravenous dose of prednisolone. The results indicate that prednisone, 6 beta-, 20 alpha- and 20 beta-hydroxyprednisolone may be the major unconjugated metabolites of prednisolone while 20 beta-hydroxyprednisone may be a minor metabolite. PMID- 1918260 TI - Novel method of purification of human leukocytic elastase using adsorption on a high-performance liquid chromatography gel permeation column. AB - Neutrophil elastases are serine proteinases released during acute and chronic inflammatory states. We have developed a novel isolation method for neutrophil elastase, involving conventional gel chromatography followed by adsorption of protein at low ionic strength on a high-performance liquid chromatography gel permeation column. The bound elastase is then eluted by application of higher ionic strength. This adsorption step at low ionic strength, a step to be avoided in most purification methods, was used to advantage here to allow isolation of homogeneous material. This purification procedure should be useful for quick, simple bulk preparation of the enzyme. PMID- 1918261 TI - Fluorimetric determination of hepatic delta-aminolevulinic acid synthase activity by high-performance liquid chromatography. AB - A fluorimetric method for measuring the activity of delta-aminolevulinic acid synthase (ALAS) in the liver of mice has been developed. The liver homogenate was used as the enzyme source. The final concentration of glycine (substrate) used for the assay was 100 mM. The delta-aminolevulinic acid (ALA) formed during incubation was converted into a highly fluorescent derivative by condensation with acetylactone and formaldehyde (application of the Hantzsch reaction). This derivative was completely separated from other fluorescent substances in the reaction medium, and it was determined using a high-performance liquid chromatograph equipped with a fluorescence monitor (370/460 nm). The activity of ALAS was expressed as nmol ALA formed per gram liver per hour. PMID- 1918262 TI - Determination of thiamine and its phosphate esters by gradient-elution high performance liquid chromatography. AB - A high-performance liquid chromatographic method for the determination of thiamine and its phosphate esters using gradient elution is presented. Chromatography was performed on an octadecyl C18 column with post-column derivatization using potassium ferricyanide: thiamine was oxidized to thiochrome, which was detected fluorimetrically. The gradient system avoids the use of a modifier and an ion-pairing reagent. The proposed method enables the separation of thiamine triphosphate, thiamine pyrophosphate, thiamine monophosphate and free thiamine, at concentrations of ca. 2 nM, within 10 min The within-assay precision for blood and serum total thiamine was less than 2 and 5%, respectively, and the between-day variation was less than 3 and 5%, respectively. The method is simple and rapid, and it can be used for screening of thiamine deficiency and for clinical study of various diseases related to vitamin B1 deficiency. PMID- 1918263 TI - Determination of styrene-7,8-oxide in whole rat blood by gas chromatography-mass spectrometry. AB - A rapid and selective method for the determination of styrene-7,8-oxide (SO) in whole blood has been developed. Blood samples as small as 0.1 ml are extracted once with benzene containing phenyl propylene oxide as an internal standard. The extracts are analyzed by gas chromatography-mass spectrometry using an automated cold on-column injection system to avoid thermal rearrangement of SO to phenylacetaldehyde. The overall mean recovery (+/- 2 sigma) of SO from fortified blood samples was 92 +/- 21% and the detection limit was 10 ng/g. Results of experiments examining the half-life of SO in whole rat blood are presented. The method was also used to analyze sequential blood samples from rats administered SO orally. PMID- 1918264 TI - Antineutrophil cytoplasmic antibody--a useful serological marker for vasculitis. AB - Systemic necrotizing vasculitides, including polyarteritis nodosa, Churg-Strauss syndrome, "overlap" systemic vasculitis, Wegener's granulomatosis, and idiopathic crescentic glomerulonephritis, are frequent clinical diagnostic problems. These diseases have diverse presentations and are often rapidly progressive, causing irreversible injury to the vessels of the kidneys and lungs before effective immunosuppressive therapy is instituted. Even in their less fulminant forms, they are a cause of significant morbidity and mortality. Antineutrophil cytoplasmic antibody, a recently identified autoantibody, has a high sensitivity and specificity for this spectrum of diseases. The clinical and pathological similarities, the high frequency of antineutrophil cytoplasmic antibody expression, and the similar good response to immunosuppressive therapy suggest that these diseases may be linked by a common pathophysiological mechanisms. Evidence is growing that antineutrophil cytoplasmic antibody plays a central role in this mechanisms. A revision in the classification scheme of vasculitides to recognize that the polyarteritis group (polyarteritis nodosa, Churg-Strauss syndrome, and "overlap" systemic vasculitis), Wegener's granulomatosis, and idiopathic crescentic glomerulonephritis are closely related diseases may be warranted. The clinical and pathological features of systemic necrotizing vasculitides and the current knowledge concerning antineutrophil cytoplasmic antibodies are reviewed. PMID- 1918265 TI - Defective T-lymphocyte signal transduction and function in leukocyte adhesion deficiency. AB - The lymphocyte function-associated antigen-1 (LFA-1) molecule is a cell surface heterodimeric protein that directly mediates cellular adhesion. However, it remains unclear whether LFA-1 molecules are also involved in transmembrane signaling and in the subsequent regulation of cellular functions. Previous attempts to evaluate this issue have been hampered by (1) the ubiquitous expression of LFA-1 on normal lymphoid cells, (2) the limited availability of assays for cellular activation that are not affected by cellular adhesion, and (3) the difficulties in interpreting studies where anti-LFA-1 mAbs are used to alternatively block or stimulate this antigen. In order to avoid these pitfalls, we first isolated and cloned T lymphocytes from a patient with leukocyte adhesion deficiency (LAD), an inherited disorder in which the defective expression of leukocyte integrins results in the production of LFA-1- T lymphocytes. Different T-cell lines from this patient and from normal individuals were then stimulated through their T-cell antigen receptor complex and were then tested for three aspects of cellular activation: (1) transmembrane signaling (i.e., phosphoinositide turnover), (2) lymphokine secretion (i.e., release of lymphotoxin), and (3) their capacity to mediate cellular cytotoxicity (using murine anti-CD3-producing hybridoma cells as targets). Using assay systems that did not involve LFA-1-mediated adhesion to antigen-presenting cells or target cells, the T-cell lines from the LAD patient were found to be intrinsically defective in all three of these parameters of T cell activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918266 TI - Acute release of cytokines is proportional to tissue injury induced by surgical trauma and shock in rats. AB - Cytokines are important mediators of the inflammatory reaction and microvascular injury after trauma and tissue ischemia. The plasma activity of a cytokine reflects the net effect of positive and negative signals. We examined the sequential serum activity of IL-1, IL-2, IL-6, and TNF in a severe model of splanchnic artery occlusion (SAO) shock induced in rats by total occlusion of the superior mesenteric and the celiac arteries for 40 min. A control group with negligible surgical intervention and two sham-shock groups, one with minor operation and another with major surgery employed in SAO rats, both without vascular occlusion, were also studied. No IL-1 activity was detected throughout the 190-min experimental protocol in any of the groups. Low activity of IL-2 was measured only in SAO rats (approximately 1 U/ml at the peak). We found graded increases in serum TNF and IL-6 activities which were proportional to the surgical trauma and were highest in SAO rats (IL-6 up to 30 U/ml, P less than 0.01 from both sham groups; TNF, 2500 pg/ml 30 min after reperfusion, P less than 0.01 from both sham groups). These data further support the role played by cytokines in the early mediation of surgical trauma and shock. PMID- 1918267 TI - Analysis of function-associated receptor molecules on peripheral blood and synovial fluid granulocytes from patients with rheumatoid and reactive arthritis. AB - In this study we report the expression pattern of 13 different function associated surface molecules on synovial fluid and peripheral blood granulocytes from rheumatoid and reactive arthritis patients. We found increased expression of the complement receptors 1 (CD35) and 3 (CD11b) and of the activation-associated antigens CD67, CD24, and M5 on synovial fluid granulocytes from rheumatoid and/or reactive arthritis patients compared to autologous peripheral blood granulocytes. In addition, synovial fluid granulocytes expressed IgG Fc receptor 1 (CD64) and complement receptor 4 (CD11c), neither of which can be found on peripheral blood granulocytes. Peripheral blood granulocytes from rheumatoid and reactive arthritis patients expressed higher levels of leucocyte function-associated antigen 1 (CD11a) and of the membrane proteins CD31, CD24, M5, and M6 compared to peripheral blood granulocytes from healthy controls and patients with degenerative joint disease. No significant differences in the expression of any of the molecules studied could be observed between cells from rheumatoid and cells from reactive arthritis patients, suggesting a similar activation process for granulocytes in these two diseases. PMID- 1918268 TI - Enumeration of human peripheral blood lymphocytes secreting immunoglobulins of major classes and subclasses in healthy children and adults. AB - The reverse enzyme-linked immunospot assay was modified to enumerate peripheral blood mononuclear cells (PBMC) secreting IgG1-4, IgA1-2, and IgM. Anti-human IgG F(ab')2 and mouse monoclonal antibodies specific to each of the isotypes were used as solid-phase capture antibodies and developing antibodies, respectively. Although attempts were also made to detect IgD- and IgE-secreting cells (SC), their numbers in the peripheral blood were too few to be reliably estimated. The assay was applied to study healthy subjects including 21 neonates within 3 days of birth, 44 1- to 48-month-old children, and 32 adults. Sixty percent of these neonates had IgM SC in small numbers (less than 20 per 10(6) PBMC), but only three neonates had IgSC of other isotypes. In contrast, by 1-2 months of age children had IgSC of all isotypes, including IgA2 and IgG4, often in higher numbers than adults. The relative frequencies of IgSC were IgA1 greater than IgG1 greater than IgM greater than IgG2 greater than IgG3 greater than IgG4 greater than IgA2 in the children and IgA1 greater than IgG1 greater than IgA2 greater than IgM greater than IgG4 greater than IgG2 greater than IgG3 in the adults. The order of the serum concentrations in the adults was IgG1 greater than IgG2 greater than IgA greater than IgM greater than IgG4 greater than IgG3. No correlation was found between the serum level and the IgSC number of individual isotypes (except for serum IgA and IgA1-SC). This new methodology should facilitate investigating the current status of immunoglobulin synthesis and the Ig repertoire in adults and children, in health and in disease. PMID- 1918270 TI - [The effects of electrical stimulation on epiphyseal cartilage]. AB - The effects of electrical stimulation on epiphyseal growth were studied. The epiphyseal cartilage of the proximal tibia of New Zealand white rabbits was stimulated by direct current for 2 weeks. A constant direct current of 5 microA was supplied by an electrical stimulation system buried under the subcutaneous tissue. Contralateral tibia with dummy electrodes served as control. The results were as follows: The height of the epiphyseal plate near the electrodes was slightly increased by traumatic reaction to the electrodes in the control group. However, in the stimulation group, the height was more remarkably increased than in the control group. The height of the epiphyseal plate was 0.6 +/- 0.2 mm in the control group, and 1.0 +/- 0.4 mm in the stimulation group, showing a statistical difference. The mineral appositional rate, determined by tetracycline labels, was 3.0 +/- 0.8 microns/day in the control group and 4.6 +/- 0.4 microns/day in the stimulation group. It was observed that the turnover of the epiphyseal plate was accelerated in the stimulation group, but no other abnormal findings were observed by electron microscopy. In conclusion, it is clear that growth of the epiphyseal cartilage is accelerated by direct current. PMID- 1918271 TI - [An experimental study on the etiology of chondromalacia patellae]. AB - Chondromalacia patellae is one of the common causes of patellofemoral disorders in young subjects. It frequently occurs in patients with lateral subluxation of the patella. However, the etiology of this disease is still obscure. The purpose of this study was to elucidate the histological changes of articular cartilage and bone in chondromalacia patellae. Lateral subluxations of the patellae were produced experimentally in forty New Zealand white rabbits. The mean tilting angle of the patellae was 14.2 degrees just after surgery, 10.7 degrees after 6 weeks, and 7.1 degrees after 12 weeks respectively. Contact pressure was lower on the medial facets than on the lateral facets and both facets of the controls. Macroscopic changes on the patellar cartilage did not appear until 12 weeks postoperatively. On the other hand, histological changes such as vascular invasion of the calcified layer, irregularity of tidemark and a decrease in the number of chondrocytes in the deep layer of the cartilage were observed on the medial facet about 4 weeks postoperatively. The degeneration of chondrocytes and matrix gradually progressed from the deep layer to the superficial layer. Twelve weeks after, a depressed area was shown in the medial facet macroscopically. Repairing process was substantiated such as the proliferation of synovial tissue, the cluster formation of chondrocytes and the recurrence of the tidemark about 30 weeks postoperatively. From the results mentioned above, it is suggested that cartilaginous and bony degeneration were caused by a decrease in contact pressure on the articular cartilage. The histological features of the chondromalacia patellae would be eventually developed by degenerative changes and restorative reaction. PMID- 1918269 TI - Light-chain ratio of serum IgA1 in IgA nephropathy. AB - Patients with primary IgA nephropathy have deposits of IgA1 in their kidneys and increased IgA1 in circulation. We had previously shown that IgA nephritic patients displayed a unique immunological response characterized by a predominance of IgA with lambda chain in glomerular deposits and in circulation. We have now studied the kappa/lambda (kappa/lambda) ratio of serum IgA1 in 21 IgA nephritic patients at quiescence, with 11 patients investigated during exacerbation as well. A novel enzyme-linked immunosorbent assay was used with monoclonal mouse anti-human IgA1 as the solid-phase capture antibody and peroxidase-labeled anti-human kappa and lambda antibodies as tracers. The ratio of serum IgA1 to total IgA (mean +/- SD) was significantly higher in patients (90.1 +/- 8.2% at quiescence, P less than 0.01; 88.7 +/- 8.1% during exacerbation, P less than 0.02) than in 20 healthy age- and sex-matched controls (80.0 +/- 9.8%). Furthermore, serum IgA1 kappa/lambda ratios were significantly lower in patients (1.02 +/- 0.27 at quiescence, P less than 0.01; 0.93 +/- 0.16 during exacerbation, P less than 0.01) than in controls (1.31 +/- 0.30). These findings indicate a predominance of lambda light-chain IgA1 in the serum of IgA nephritic patients. However, no difference in IgA1 kappa/lambda ratio was observed in these patients at quiescence and during exacerbation. PMID- 1918272 TI - [Clinical features and treatment of ventricular tachycardia associated with acute myocardial infarction]. AB - Three hundred and ninety-two consecutive patients with acute myocardial infarction (AMI) were studied to delineate the clinical features of ventricular tachycardia (VT) (three or more VPC). The incidence of VT in AMI was 23.5% and was higher in inferior AMI (29.8%) than in anterior AMI (19.3%) (p less than 0.05). The incidence of ventricular fibrillation (VF) and mortality were higher in the VT group than in the non-VT group. VT was most frequent on the first day after the onset of AMI. However, another peak of the occurrence of VT was observed in the 4th week after AMI in the anterior AMI group, but not in the inferior AMI group. The late-onset VT had a rapid heart rate during the VT attack (209 +/- 42 vs 170 +/- 62 beats/min, p less than 0.05) which frequently developed to VF (20.9 vs 8.4%, p less than 0.05). This was associated with severe heart failure and indicated a poor prognosis (mortality; 75.0 vs 24.2%, p less than 0.01), when compared with VT that occurred in the early period after the onset of AMI. The effectiveness of the thump-version for the termination of VT was 60.9%. Lidocaine was effective at 57.1%. PMID- 1918273 TI - [Prediction of ventricular tachycardia in acute myocardial infarction by ventricular late potentials]. AB - To know the relationship between positive ventricular late potentials (LP) and occurrence of ventricular tachycardia (VT), signal-averaged electrocardiogram (SAECG) was recorded in 214 patients with myocardial infarction (MI). According to the time course of SAECG recording after the onset of MI, the subjects were divided into three groups; acute MI (AMI) group (onset-2nd week, n = 148), recent MI (RMI) group (3rd-6th week, n = 19) and old MI (OMI) group (7th week or later, n = 47). The incidence of positive LP in each group was 22.3%, 36.8% and 12.8%, respectively. VT was observed in 51.5% (AMI), 71.4% (RMI) and 83.3% (OMI) in LP positive patients, and these proportions were significantly higher than those (25.2%, 0% and 9.8%) in LP negative patients. Sensitivity, specificity and predictive accuracy of positive LP to predict occurrence of VT were 37.0%, 84.3% and 69.7% in AMI, 100%, 85.7% and 89.5% in RMI and 55.6%, 97.4% and 89.5% in OMI, respectively. Incidence of positive LP in the patients with inferior infarction (23.9%) or with combination of inferior and anterior infarction (60.0%) were significantly higher than those in patients with anterior infarction alone (13.9%). Significantly higher peak-CPK value (4333 +/- 2580 IU/L) in the patients with positive LP compared to those with negative LP (2438 +/- 2023 IU/L) suggests that patients with positive LP have an infarction of larger size. In conclusion, non-invasive LP detection using signal averaging technique was useful in prediction of occurrence of VT in patients with MI in any phase. PMID- 1918274 TI - [Studies on wedged hepatic venous pressure, hemodynamics and pulmonary function in patients with chronic liver disease, with reference to the differences between liver cirrhosis with chronic hepatitis]. AB - In 17 compensated liver cirrhosis and 8 chronic hepatitis cases (no histories of cardiac or pulmonary disease), wedged hepatic venous pressure (WHVP), hemodynamics, and pulmonary function were measured and their clinical significance and interrelations evaluated. Both diseases were comparatively analyzed. WHVP was determined by wedging a catheter from the right femoral vein into the right hepatic vein. Hemodynamics was measured with a Swan-Ganz catheter. Spirography, flow-volume curve, closing-volume curve and pulmonary diffusion capacity were measured and aortic blood gas analyzed to assess pulmonary function. Esophageal endoscopy was used to diagnose the presence or absence of esophageal varices. The results showed that the group of liver cirrhosis patients featured elevated WHVP and a hyperhemodynamic pattern and a positive correlation between WHVP on the one hand and cardiac index and right left ventricle stroke work indexes on the other; there was a negative correlation between WHVP and the systemic vascular resistance and pulmonary vascular resistance indexes. The results showed an increase in oxygen consumption in the group of patients with esophageal varices. In all chronic hepatitis cases, findings were normal. Pulmonary function was characterized by abnormal %VC, PaO2, and pulmonary diffusion capacity in both groups along with abnormal PaCO2 in the liver cirrhosis group; no significant differences were noted between the two groups. These results indicate that liver cirrhosis elevates intarahepatic pressure, affecting systemic hemodynamics and resulting in a circulatory distribution disorder, leading to right and left ventricle overload and a decline in potential cardiac function. The results also indicated that mild pulmonary function disorder can occur as early in a state of chronic hepatitis. PMID- 1918275 TI - [A study of a systemic fibrinolytic treatment of acute myocardial infarction. The effect of a moderate dose infusion of urokinase]. AB - The clinical efficacy of intravenous fibrinolytic treatment using a moderate dose of urokinase (UK) on acute myocardial infarction (AMI) has not been well evaluated in randomized trials. In order to assess the efficacy of UK, a prospective randomized study was undertaken, aimed mainly at evaluating coronary myocardial blood flow in the infarcted myocardium using Tl-201 myocardial scintigraphy. 166 patients (131 male and 35 female, mean age 61.1 years) with AMI classified in Killip I or II who were admitted to the CCU within 24 hours of the onset of symptoms were divided into two groups; 76 patients treated with UK (UK group) and 90 patients treated with conventional therapy without UK (control group). Intravenous UK 72,000 IU was injected over 10 minutes and UK 528,000 IU was subsequently given by drip infusion over the following 12 (n = 36) or 24 hours (n = 40). There was no significant difference between the two groups with regard to the patients' background. Tl-201 uptake of infarcted myocardium in the UK group (n = 17) significantly increased in the first week compared with that on the day of admission (p less than 0.005) and a further significant increase was observed in the fourth week (p less than 0.05). In the control group (n = 10) Tl 201 uptake did not change in the first week and then increased significantly in the fourth week (p less than 0.05). Coronary angiography and left ventriculography (43 cases in the UK group and 32 cases in the control group) performed in the convalescent stage of AMI showed: 1) similar prevalence of patency of the infarct related artery (UK group: 72.1%, control group: 75.0%), 2) more prominent collateral circulation in the UK group (62.9% vs 41.4%), 3) significantly better perfusion of infarcted myocardium by coronary antegrade flow and/or collateral flow in the UK group (70.0% vs 46.9%, p less than 0.05), 4) a trend towards reduction of severe asynergy in the infarcted regional wall of the left ventricle in the UK group (16.3% vs 34.4%). The mortality rate of patients with first AMI in the UK group (n = 66) was significantly lower than that in the control group (n = 68) (4.5% vs 14.7%, p less than 0.05), and a similar trend was also found in patients with prior infarction (UK: n = 10, 0% vs control: n = 22, 13.6%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1918277 TI - [The review process and some consideration of the assessment in committee on clinical practice of investigational new drugs in Nippon Medical School]. PMID- 1918276 TI - [Treatment of superficial bladder tumor]. AB - In period of April, 1982 to March, 1987 for 5 years, fifty-four patients with superficial bladder tumors were treated at the Department of Urology, Nippon Medical School. There were 42 males and 12 females with age ranged from 28 to 85 years old. All patient underwent TUR-Bt (trans urethral resection-bladder tumor) as an initial treatment. The rather long term follow-up study after initial treatment was 47 months in average. Recurrence rate at 2 years after TUR-Bt was 30%. The risk factors of recurrence were analysed in connection with sex, age, tumor number, histological grade and stage, and infiltration pattern. In conclusion, significantly higher recurrence rate were observed in G2 than G1 and G3, and in pT1b rather than pTa and pT1a. Other factors were not distinctly correlated with incidence of recurrence. PMID- 1918278 TI - [Endothelium derived relaxing factor and L-arginine]. PMID- 1918279 TI - Visual hierarchical analysis of Block Design configural errors. AB - Patients have been frequently observed to violate the overall configuration on the WAIS-R Block Design subtest. The significance of these configural errors was investigated with hierarchical patterns consisting of large "global" shapes made from smaller "local" shapes. Subjects were administered two similarity judgment tasks in which they were asked to decide which of two hierarchically structured comparison figures most resembled a standard figure. Results indicated that subjects who made configural errors on Block Design were less likely than a matched sample who did not make configural errors to select the comparison figure that resembled the standard figure at the global level. Furthermore, the present findings were obtained from subjects without known right-hemisphere lesions, suggesting that the correlation between Block Design errors and global/local performance is applicable to a broad range of patient and non-patient populations. The data are consistent with the view that errors on Block Design may reflect differences in the perceptual encoding of global/local features. PMID- 1918280 TI - The association of memory complaint with computer-simulated everyday memory performance. AB - The relationship of memory self-report to self-rated depression and to actual performance on computer-simulated everyday memory tasks was investigated in 125 normal adults. Canonical correlation analyses demonstrated that self-rated memory performance and objective computer-simulated everyday memory performance shared from 27.9% to 29.4% of common variance. These data provide initial concurrent validity for a new memory self-report scale, the MAC-S. Results are discussed in relation to psychometric factors important in the design and validation of self report memory scales. PMID- 1918281 TI - Chronic occupational exposure to manganese and neurobehavioral function. AB - Comprehensive examinations of neurobehavioral function were performed in two groups of workers with chronic exposure to industrial manganese, and two control groups. Group 1 included 17 exposed workers without parkinsonism while Group 2 consisted of four exposed workers with parkinsonian syndrome resulting from chronic manganese poisoning. Group 3 was composed of eight idiopathic parkinsonian patients while Group 4 included 19 control subjects. Age, sex, and educational level of these four groups were matched. The neuropsychological battery consisted of tests of orientation, intelligence, learning and memory, language and communication, visuospatial and visual perception, visual attention, manual dexterity, and information processing speed. There was no evidence of neurobehavioral impairment in the non-parkinsonian workers whereas impaired general intelligence, visuoperceptive impairment and defective manual dexterity, as well as slowdown in response speed were manifested in the parkinsonian workers. PMID- 1918282 TI - Encoding specificity, depth of processing, and cued recall in Alzheimer's disease. AB - Unlike normal aging, Alzheimer's disease (SDAT) subjects typically show no benefit in free recall from semantic depth of processing cues at acquisition, but their recall is enhanced by semantic cues at both acquisition and retrieval. However, this apparent encoding-specificity effect might result from cued recall alone. SDAT and control subjects studied pictures in a design comparing depth of processing, cued recall, and encoding specificity. Cued recall alone was ineffective for SDAT subjects but, consistent with other studies, the encoding specificity condition did enhance recall. Both control and SDAT subjects also showed a levels of processing effect in free recall, modified by recency of presentation. Conclusions were: (a) though impaired in the capacity spontaneously to do so, SDAT subjects can be assisted to exploit semantic aspects of material in memory; (b) for optimal remembering in SDAT, substantial cued support should be provided at both ends of the processing continuum. PMID- 1918283 TI - Head injury and spinal cord injury: differential effects on psychosocial functioning. AB - Closed-head injury (CHI) and spinal cord injury (SCI) cause significant permanent alterations in life style, social-role functioning, and psychological status. While the cognitive effects of CHI are well known, there have been questions concerning the psychosocial sequelae from CHI, and whether they are unique to this disability group rather than representing general effects of a life threatening medical emergency with permanent life-altering consequences. This issue was examined with samples of ambulatory moderate (n = 31) and severe (n = 17) CHI patients and wheelchair-dependent SCI (n = 24) patients. Results indicate that there were no significant differences between the groups on pre- and post injury demographic factors. However, while the moderate CHI and SCI groups were equivalent on many indicators of psychosocial outcome, the severe CHI group was more depressed, angry and hostile, and confused and bewildered. As well, wives of the severe CHI patients rated their husbands as more belligerent, negative, helpless, suspicious, withdrawn and retarded, and with more general psychopathology than did wives of moderate CHI or wives of SCI patients. Implications of these findings for preventative psychosocial rehabilitation are discussed. PMID- 1918284 TI - Positron emission tomographic studies during serial word-reading by normal and dyslexic adults. AB - Positron-emission tomography (PET) was used to study regional cerebral metabolic activity during oral reading in right-handed adult males with, and without a childhood and family history of developmental dyslexia. Significant group differences in normalized regional metabolic values were revealed in prefrontal cortex and in the lingual (inferior) region of the occipital lobe. Lingual values were bilaterally higher for dyslexic than normal readers. In contrast to the asymmetry observed in prefrontal and lingual regions in nondyslexic subjects during reading, the dyslexic pattern was more symmetric. These results demonstrate that individuals who suffered from familial developmental dyslexia as children, activate different brain regions during reading as adults, as compared to individuals without such childhood history. PMID- 1918286 TI - Semantic organization and verbal episodic memory in patients with mild and moderate Alzheimer's disease. AB - The objective of the present research was to investigate the relationship between semantic organization and cue utilization in mildly and moderately demented patients with Alzheimer's disease (AD). In Experiment 1, subjects were presented with two lists of words: a list with semantically unrelated words and a list with words from four semantic categories presented randomly intermixed. Free recall was assessed and following the organizable list, subjects received a cued recall test. Normal controls, as opposed to mildly and moderately demented patients, showed higher performance in the organizable list as compared to the random list. In addition, normal controls and mildly demented patients benefited from semantic cues in the organizable list and performed at a higher level in total recall as compared to free recall. In Experiment 2, subjects were presented with two lists of words: a list with words from four semantic categories presented randomly intermixed and a list with words from four semantic categories presented clustered, together with information about the organization of the list. Free recall and cued recall, with the category names serving as cues, were assessed. Free recall performance of normal controls was higher in the clustered than in the organizable list, whereas no such effect was observed for the AD patients. Normal controls and mildly demented patients performed at a higher level in total as compared to free recall in both lists, whereas this effect was present only in the clustered list for the moderately demented patients. The overall pattern of results indicates that there are conditions under which memory facilitation from semantic organization may be obtained in AD. PMID- 1918285 TI - Dissociable face processing impairments after brain injury. AB - Matched populations of head-injured patients and normal control subjects completed three "forced-choice" face processing tasks designed to test facial expression recognition, familiar face recognition, and unfamiliar face matching. We hypothesised a significant difference in the performance of the patients and controls on the three tasks, and hoped to observe individual differences in the patients' performance across tasks. As predicted the head-injured patients made significantly more errors than the controls on the forced-choice tasks. Four cases of dissociable impairments affecting only one of the face processing tasks are reported; patient JP impaired only on facial expression recognition, patients AB and HI impaired only on familiar face recognition, and patient VS impaired only on unfamiliar face matching. These dissociable impairments provide further evidence for independent cognitive processing of specific face properties. PMID- 1918287 TI - Hippocampal contribution to verbal recent memory following dominant-hemisphere temporal lobectomy. AB - The effects of hippocampal encroachment in the language dominant-hemisphere were studied in 41 patients who underwent previous temporal lobectomy (TL). Patients undergoing dominant-hemisphere TL including anterior hippocampus (n = 13) performed significantly worse than nondominant TL patients (n = 16) on a verbal learning test (Selective Reminding; p less than or equal to .00001), thereby confirming the sensitivity of this procedure to lateralized temporal-lobe dysfunction. However, no significant difference was present on this or other primary measures of material-specific memory when contrasting dominant TL patients in whom the anterior hippocampus was spared (n = 12) to those in whom anterior hippocampus was resected. These data suggest that more extensive and posterior mesial temporal-lobe resection is not necessarily associated with a greater verbal material-specific memory deficit following dominant-hemisphere temporal lobectomy. PMID- 1918288 TI - Four studies comparing the Rey-Osterrieth and Taylor complex figures. AB - The ability of the Rey-Osterrieth (R-O) and Taylor complex figures to produce equivalent scores on both constructional and memory tasks was examined in four studies. While the two figures yielded equivalent copy scores, the Taylor figure produced significantly higher scores on memory tests. This latter relationship was observed with three different retention conditions (immediate, 20-min, and 1 month recall), two types of learning paradigms (incidental and intentional), and two scoring systems (itemized and clinical neuropsychological). The failure to obtain equivalent recall scores cautions against using the R-O and Taylor as companion figures to evaluate normal recovery and treatment effectiveness on mnemonic processes. The relative merits of using an intentional rather than an incidental procedure to administer the figures in test-retest situations are discussed. PMID- 1918289 TI - Does processing style affect recall of the Rey-Osterrieth or Taylor complex figures? AB - This study investigated the effects of visual vs. verbal processing style preferences on immediate recall accuracy for the Rey-Osterrieth and Taylor Complex Figure Tests. Undergraduates were classified as visualizers or verbalizers and asked to copy either the Rey-Osterrieth or Taylor figure and then draw it from memory. A subset of subjects reported the strategy they used to reproduce the figure. Visualizers showed better reproduction accuracy than verbalizers for the Rey-Osterrieth test, and for this test approximately 80% of verbalizers as well as visualizers reported using a visual strategy. For the Taylor, no effect of processing style was obtained, and close to half of the verbalizers (43%) reported using their preferred verbal strategy, while 82% of the visualizers used a visual strategy. These results suggest that a general preference for thinking "in images" is important for predicting visual memory accuracy only on tests such as the Rey-Osterrieth which do not lend themselves easily to a verbal strategy. In contrast, for the Taylor test, deficits to the visual imagery system may be circumvented and obscured by the verbalizers' use of verbal recall strategies. Thus, in test batteries, the Rey-Osterrieth and the Taylor Tests should not be used interchangeably. PMID- 1918290 TI - Neuropsychological functioning of hydrocephalic children. AB - A group of 30 five- to eight-year-old hydrocephalic children was administered a comprehensive battery of neuropsychological tests. As a group, they displayed a pattern of lower PIQ than VIQ. Their performance was within the average range of many neuropsychological tests, but they performed poorly on some measures of complex visuospatial functioning. It is concluded that hydrocephalic children at this early age exhibit relatively reduced efficiency in processing complex or novel nonverbal stimuli. The possibility of dysfunction in the posterior regions of the right cerebral hemisphere is discussed. PMID- 1918291 TI - Interpretation of outcome on dichotic listening tests following stroke. AB - The historical basis for interpretation of the dichotic listening performance of aphasic patients is presented. Most studies agree with respect to outcome; aphasic patients as a group tend to have ear advantages (EAs) that are shifted to the left relative to non-brain-damaged listeners. Studies disagree as to whether this difference reflects a shift toward right hemisphere dominance for language processing or a "contralateral ear lesion effect." Emphasis is placed on the most recent additions to the literature, including discussion of factors that affect the accuracy with which lesions can be localized. The conclusion reached is that variables other than dominance determine the direction of ear advantage for many aphasic listeners. PMID- 1918292 TI - The WAIS-R profile as a cognitive marker of Alzheimer's disease: a misguided venture? AB - The utility of a pattern on WAIS-R subtest performance (Fuld profile) in differentiating between dementia of the Alzheimer's type (DAT) and multi-infarct dementia (MID) was investigated. The Fuld profile was neither sensitive nor specific to DAT, as similar numbers of DAT subjects (15%) and MID subjects (12%) obtained a positive profile. No relationship between presence of the profile and level of education was detected. However, a positive profile in DAT subjects was associated with less severe neuropsychological impairment. Implications of this finding as well as the value of searching for a cognitive marker for DAT are discussed. PMID- 1918293 TI - Relationship of constructed follicular growth patterns in stimulated cycles to outcome after IVF. AB - The growth patterns of 827 follicles have been constructed from ultrasound measurements made between day -7 and day -2 of the follicular phase (oocyte aspiration = day 0) as a part of the routine treatment of 107 in-vitro fertilization (IVF) patients. A distinctive pattern of growth which was characterized by rapid early growth and a later growth consistent with the 'conceptual pattern' of growth described by Zegers-Hochschild (1984) for natural cycles was shown to be highly correlated with a delivered pregnancy outcome. Every cycle where a delivered pregnancy resulted (n = 9) produced one or more follicles with this pattern of growth (11/69 follicles, 16%). In contrast, only 20% (20/98) of cycles with any other outcome (abnormal pregnancy, no pregnancy, no embryo formed) appeared to have a follicle conforming to this pattern (27/758 follicles, 3.6%). These observations suggest that the follicle growth pattern, with particular emphasis on the rate of early growth, may be a highly predictive indicator of the quality of follicle development and the subsequent pregnancy potential of the oocyte contained within. PMID- 1918294 TI - Menopausal flush symptomatology and sustained reflex vasoconstriction. AB - Reflex vasoconstriction was examined using the digital vasoconstrictor response to ice application in 102 postmenopausal women. Women experiencing hot flushes tended to lack the normal vasoconstrictor response whereas women with lower flush symptomatology tended to have a vasoconstrictor response. There was a significant relationship between the percentage occurrence of a vasoconstrictor response and both the daily flush score (P less than 0.001) and subjective severity of flushes (P less han 0.001). PMID- 1918295 TI - Post-partum cervical mucus: biological and rheological properties. AB - In this study we have evaluated the score, sperm migration and ultrastructural characteristics of cervical mucus present in amenorrhoeic women under exclusive breastfeeding at 30, 60, 90, 120, 150 and 180 days post-partum. Periovulatory mucus samples from seven normally cycling women were used as a control. The average scores of post-partum and periovulatory mucus were 4.6 +/- 0.4 and 14.1 +/- 0.5 respectively. Twenty-one (39%) of the 54 post-partum cervical mucus samples and all (100%) periovulatory mucus samples allowed sperm migration. Positive sperm migration into post-partum mucus was observed at all time intervals studied. The only parameter that correlated with sperm migration into post-partum mucus was ferning formation. Sperm migration was obtained in all post partum mucus samples with a score greater than 8, but samples with scores between 2 and 7 also showed sperm penetration. Scanning electron microscopic studies showed the characteristic spongy appearance of periovulatory mucus. Post-partum mucus was formed by a dense mesh (rocky appearance), when samples were generally unable to sustain sperm migration, but samples where sperm migration occurred showed small areas of spongy mucus mixed with areas in which a dense mesh and high cellularity was observed. PMID- 1918296 TI - Tissue effects of methotrexate injected into the uterine horn of pregnant female rats. AB - Methotrexate has been proposed as a treatment for unruptured extra-uterine pregnancy, but its effects on the tubal wall remain unknown. In order to analyse these effects, an experimental study was carried out on two groups of pregnant female rats, one receiving methotrexate (n = 8) and the other sodium chloride (n = 6). In both groups, a single intra-embryonic injection was performed in the uterine horn. The genital tract was prepared for histological examination. In all rats which received a single dose of methotrexate (5 mg per 100 g body weight) six days after mating and were killed nine days later, the labyrinthine part and the junctional zone of the placenta were necrotic at the site of the injection, with no embryonic development. The other parts of the genital tract were not visibly altered. In rats receiving sodium chloride and killed under the same conditions, necrosis of the placenta was observed at the site of injection in three animals. In the other three rats, a focal necrosis of the placenta was found, which was probably of mechanical origin. From this study, we conclude that methotrexate is efficient in killing normally implanted embryos and is, at least under light microscopy, non-toxic to the adjacent portions of the genital tract. PMID- 1918298 TI - Triggering ovulation with endogenous luteinizing hormone may prevent the ovarian hyperstimulation syndrome. AB - In a series of 126 therapeutic cycles in 48 patients with primary infertility and treated with HMG for anovulation or preparation to insemination, ovulation was triggered by endogenous LH instead of HCG when the patient was considered to be at high risk for ovarian hyperstimulation syndrome (OHS), (plasma oestradiol greater than 1200 pg/ml) and/or multiple pregnancy (greater than 3 follicles greater than 17 mm in diameter). The endogenous LH surge was provoked and maintained by intranasal buserelin 200 micrograms three times at 8-hourly intervals. In the 37 cycles with buserelin, no OHS occurred despite high preovulatory levels of oestradiol; a single twin pregnancy was recorded despite the presence of numerous mature preovulatory follicles. Conception results (21.6% pregnancy per therapeutic cycle) compared favourably with HCG administration (16.8%). It is concluded that, when ovulation must be triggered in a hazardous situation, the use of endogenous LH through the administration of a short-acting GnRH analogue prevents the complications of exaggerated follicular stimulation. PMID- 1918297 TI - Evaluation of the luteal phase. AB - The values of various methods used to evaluate the luteal phase, including basal body temperature, measurement of progesterone (P), endometrial biopsy, ultrasonographic measurement of endometrial thickness, and measurement of endometrial proteins, are reviewed. Luteal phase defect (LPD) is a controversial entity. The diagnosis of this condition is best based on a histological study of the endometrium. Methods to improve the accuracy of the diagnosis are discussed. LPD is more likely to be a result of an abnormal response of the endometrium to P, than to a subnormal production of P by the corpus luteum. Many methods of treatment for LPD have been proposed but none is based on a properly controlled clinical trial. Treatment designed to improve the response of the endometrium to P may be more rewarding than P supplementation. PMID- 1918300 TI - Comparison of a rapid, quantitative and automated assay for urinary luteinizing hormone (LH), with an LH detection test, for the prediction of ovulation. AB - The prediction of ovulation is necessary for oocyte aspiration in a spontaneous cycle and can be reliably achieved only by measuring luteinizing hormone (LH). Since radioimmunoassays of LH take too long for repeated measurements on the same day, we evaluated the possibility of adapting a rapid and fully automated assay of serum LH for use with urine samples. The study group comprised spontaneously ovulating women (38 cycles) who requested artificial insemination. Their serum oestradiol (E2) levels, ultrasound profile (US) and thrice daily urinary LH levels were determined from day 10 of their menstrual cycle. These patients were followed until US signs of follicular rupture were recorded. In all patients, a well-defined LH peak was measured in the urine. This peak lasted 12-15 h and was followed in 35 cycles (no US available for 3) by follicular rupture 9-51 h later. The data were grouped according to the time of the LH peak on day 0. Patients experiencing an LH peak between 0300 h and 0700 h on day 0 had significantly lower levels of E2 on day 0 compared to those with an LH peak between 2200 h and midnight. This is due to the fact that in the patients with an LH peak between 0300 h and 0700 h, E2 levels were already decreasing (from day 1 to day 0), whereas in those with the LH peak between 2200 h and midnight E2 levels were still increasing on the morning of day 0. We conclude that the 30-min IMX LH assay is a reliable, rapid and readily acceptable method for measuring urinary LH and for the prediction of ovulation. PMID- 1918299 TI - Correlation of serum progestagen-associated endometrial protein levels with endometrial biopsies serum steroid levels and therapy for luteal phase defects. AB - The progestagen-associated endometrial protein (PEP) level rises from the early to the late luteal phase. A study was performed in infertile women where late luteal phase endometrial biopsies and serum PEP levels were obtained. The objective of the study was to evaluate the correlation between the PEP levels and the endometrial biopsies and to determine if subnormal PEP levels could be improved by the same therapies used to correct endometrial defects. There was a poor correlation between PEP levels and endometrial biopsies (r = 0.17). Similarly, there was no significant correlation between PEP levels and levels of the following hormones: mid- and late-luteal phase progesterone (P) (r = 0.186 and 0.282 respectively), mid-luteal phase 17-hydroxyprogesterone (17-OHP) (r = 0.139) and mid-luteal phase oestradiol (r = 0.135). Furthermore, there was no correlation between PEP levels and the dosage of progesterone used in therapy (r = 0.07). There were no statistically significant differences in PEP values (U/ml) depending on whether any fertility drug was taken. Thus our data suggest that progesterone may only have a permissive role, with some other factor(s) controlling the actual rise and fall of PEP. PMID- 1918301 TI - Follicular fluid prostaglandin E2:prostaglandin F2 alpha ratio in relation to outcome of matched oocyte. AB - The prostaglandins PGE2 and PGF2 alpha and the steroid hormones oestradiol (E2) and progesterone (P) were measured in 345 follicular fluids of patients undergoing ovarian hyperstimulation for in-vitro fertilization (IVF). The measured concentrations were analysed in relation to the outcome of the matched oocyte. Progesterone levels were significantly lower in the unfertilized group (P less than 0.005) compared to the fertilized group but there was no difference between 'pregnancy' and 'no pregnancy'. No differences were shown in either E2 levels or the E2:P ratio. No significant differences were shown among the groups in the concentration of either PGE2 or PGF2 alpha but there were highly significant differences shown when the PGE2:PGF2 alpha ratios were compared. The PGE2:PGF2 alpha ratio fell within a much narrower range for the 'pregnancy' group compared with any of the other groups. The ratio was significantly lower (P less than 0.001) when 'pregnancy' was compared with 'no pregnancy'. The range of the prostaglandin ratio found for the 'pregnancy' group may reflect the moment when conditions are optimal within the follicle for the associated oocyte to go on to establish pregnancy. PMID- 1918303 TI - Pregnancy after direct intraperitoneal insemination. AB - Direct intraperitoneal insemination (DIPI) and superovulation are simple procedures which may together represent a good alternative to gamete intra Fallopian transfer (GIFT) in infertile women with patent Fallopian tubes. In the present study, pregnancy occurred in 25 of 96 couples (26%) and six (24%) of these aborted. The pregnancy rate for all cycles was 19.6% and multiple pregnancies were found in six of 25 (24%) patients. We observed no ectopic pregnancy. The combination of these techniques is concluded to be useful in achieving pregnancy in infertile women with patient Fallopian tubes. PMID- 1918302 TI - Co-treatment with growth hormone of sub-optimal responders in IVF-ET. AB - Several growth factors augment the ovarian response to gonadotrophins and growth hormone is known to regulate the production of insulin-like growth factor-1. With this in mind, 20 women who had previously responded sub-optimally to standard ovarian stimulation regimens for in-vitro fertilization and embryo transfer (IVF ET) were recruited into a randomized trial to study the effect of co-treatment with growth hormone (Norditropin, Novo Nordisk Gentofte A/S). Intramuscular injections of growth hormone (24 IU) or placebo were given on alternate days concurrently with the same daily dosage of gonadotrophin as administered in the patient's pretreatment cycle. Overall, there was no improvement in the ovarian response to the growth hormone-augmented regimen of stimulation although there was a tendency for the development of more follicles (P = 0.06). When the results from the patients with ultrasound-diagnosed polycystic ovaries were analysed separately, however, more follicles developed (P = 0.04), more oocytes were collected (P = 0.03) and there was a trend towards higher urinary oestrogen production following growth hormone therapy. There was no improvement in the ovarian response in patients with normal ovaries. The treatment was not associated with any adverse effects. We conclude, therefore, that in a subgroup of patients who respond sub-optimally to standard ovarian stimulation regimens for IVF-ET and who have ultrasound-diagnosed polycystic ovaries, systemic growth hormone is an effective adjunctive therapy. PMID- 1918304 TI - 'Blind' transcervical transfer of gametes in the fallopian tube: a preliminary study. AB - The aim of the study was to assess, in a small number of volunteers, the feasibility of transferring gametes by blind transcervical tubal catheterization. Forty patients underwent ovarian stimulation with a combination of a luteinizing hormone-releasing hormone analogue and exogenous gonadotrophin. Twenty-six patients were submitted to echographical oocyte retrieval and subsequent blind transcervical tubal transfer of the gametes. Successful cannulation of the tube was achieved in 18 subjects, at the first attempt and in four subjects at the second attempt; in the remaining four subjects, three or more attempts were needed. No complications were recorded during the tubal transfer. Seven clinical pregnancies (27% of all transfers) were obtained: three ended in abortion (11%), one was ectopic (4%) and three were ongoing (11%). These preliminary results encourage larger studies using this approach. PMID- 1918306 TI - Chromosome analysis in human oocytes unfertilized in vitro: a mathematical model for the estimation of the first meiotic non-disjunction frequency. AB - The results of cytogenetic analysis of unfertilized human oocytes in an in-vitro fertilization programme are to a large extent influenced by the methodology used. Exact conclusions cannot be drawn due to technical and interpretational errors. A mathematical model was constructed, therefore, to estimate the weight of these errors and to calculate the exact frequency of first meiotic non-disjunction in IVF oocytes. Of 246 prepared oocytes only 105 could be karyotyped exactly. Using the classical method of calculation, an aneuploidy frequency of 39% was obtained. By applying the maximum likelihood method a correlation between the frequency of first meiotic non-disjunction and the interpretational error level was found. Loss of chromosomes by anaphase lagging seemed to be undetectable, but the probability of chromosome loss due to fixation and unhomogeneous spreading was found to be 20%. Accepting an error level of 10-20%, the true non-disjunction frequency expected should range between 20 and 40%. This model yields a standard curve which can offer a basis for comparison of results obtained in different studies. PMID- 1918305 TI - Prevalence and genesis of endometriosis. AB - A group of 1542 pre-menopausal Caucasian women were assessed prospectively to investigate the prevalence of endometriosis. The women were either having laparoscopy because of infertility (n = 654), undergoing laparoscopic sterilization (n = 598), having laparoscopy because of chronic abdominal and pelvic pain (n = 156) or undergoing abdominal hysterectomy for dysfunctional uterine bleeding (n = 134). Endometriosis was noted more frequently among women being investigated for infertility (21%) than among those undergoing sterilization (6%). Among those being investigated for chronic abdominal pain, the incidence of endometriosis was 15%, while among those undergoing abdominal hysterectomy, it was 25%. In all groups the total duration of combined pill usage was significantly higher in patients who had a normal pelvis compared to those with endometriosis. It is suggested that among susceptible women, both fertile and infertile, a prolonged period of regular spontaneous menstruation may play a causative role in the genesis of endometriosis. PMID- 1918307 TI - Incidence of numerical chromosome anomalies in human pregnancy estimation from induced and spontaneous abortion data. AB - Induced abortion data provided an estimate of 4.7% numerical chromosome anomalies for women with a clinically recognized pregnancy at the end of the 7th week after the last menstrual period (LMP). This frequency requires that 51.9% of spontaneous abortions occurring after the 7th week should be chromosomally abnormal if the frequency of numerical chromosome anomalies at term (live and stillbirths combined) is 0.53%. Cytogenetic data from surveys of spontaneous abortion suggested a lower incidence of 39.7%. However, this figure is likely to be an underestimate because chromosome anomalies are almost certainly over represented among the many early abortuses which lack embryonic tissue and hence are not karyotyped. The frequency of numerical chromosome anomalies at conception, arising from meiotic errors, was estimated from sperm karyotype data combined with information on the relative frequencies of maternal and paternal errors in the aetiology of trisomies. This provided a minimum estimate of 20%. PMID- 1918308 TI - Laparoscopic adnexectomy in a prepubertal Turner mosaic female with isodicentric Y. AB - Laparoscopic adnexectomy was performed in a prepubertal girl with mosaic Turner's syndrome containing an isodicentric Y chromosome. Cytogenetic analysis of lymphocytes and streak gonads are discussed. PMID- 1918309 TI - Cytogenetic analysis of unfertilized human oocytes. AB - Cytogenetic studies were carried out on 180 oocytes that appeared unfertilized after in-vitro fertilization. The majority of the 135 that were informative had grossly haploid second meiotic metaphases, two were grossly diploid, and five had a variety of different abnormalities. Twenty-one oocytes were abnormally fertilized and included prematurely condensed sperm chromosomes. The frequency of this phenomenon varied according to the stimulation protocol, those oocytes maturing longer in vivo showing less propensity to abnormal fertilizations. Thirteen per cent of the analysable haploid metaphases were hyperhaploid but none contained extra whole chromosomes. The extra components were a single chromatid (one case), or two single chromatids replacing a whole chromosome (four cases). The data suggest that the chromatids arose as a result of premature centromere division at meiosis I, and that this may be a major mechanism for trisomy formation rather than non-disjunction of whole bivalents at meiosis I, as generally believed. PMID- 1918311 TI - Sperm morphology and IVF pregnancy rate: comparison between Percoll gradient centrifugation and swim-up procedures. AB - Many groups currently use two methods for the separation of motile spermatozoa, swim-up (S-up) and centrifugation on discontinuous Percoll gradient (PGC), and comparison of results indicates that PGC is superior. In this study we have attempted to identify the factors explaining this difference. This laboratory has long-standing expertise in seminology, thus the parameters of sperm morphology were the obvious first choice for detailed study. First, the respective effects of S-up and PGC on sperm morphology were analysed in different types of ejaculates: 62 semen samples with normal parameters and 41 with poor parameters. Both separation techniques resulted in improved morphology in the final preparation but only the increase of morphologically normal spermatozoa in the final Percoll suspension was significant. Second, application of these techniques in our in-vitro fertilization (IVF) programme revealed that, together with the improvement of sperm morphology, a higher pregnancy rate was obtained after PGC. The ongoing pregnancy rates per oocyte retrieval were 21.1% for the S-up technique and 33.3% for the PGC technique. These data show that spermatozoa selected by PGC present an improved morphology which we believe to be linked to improvement of the quality of the in-vitro fertilized embryos and ultimately the percentage of successful IVF results. PMID- 1918310 TI - Endometrial ablation to control excessive uterine bleeding. AB - The use of surgical techniques is described for the management of dysfunctional uterine bleeding by endometrial ablation as alternatives to hysterectomy. Current approaches include the neodymium yttrium aluminium garnet (Nd:YAG) laser and resection by electrosurgery using a ball-end electrode. Of 484 patients treated since 1985, 361 (74%) became amenorrhoeic with only occasional spotting 68 (14%) reported satisfactory results with 55 (12%) reporting an unsatisfactory outcome. PMID- 1918312 TI - Ontogeny of mouse caudal proteins identified by a monoclonal antibody. AB - A monoclonal antibody (mAb) D2G4 directed to human spermatozoa recognized antigens on the acrosomal region of both human and mouse spermatozoa and reacted with two proteins of molecular weights 45 kd and 26 kd. Immunohistochemical staining with this antibody indicated that only the epithelial cells of the cauda epididymis were stained and not the sections of testis, caput or corpus epididymis. These observations suggest that antigens recognized by D2G4 were acquired by the spermatozoa during their passage through the cauda epididymis and appear to have a role in the maturation of spermatozoa. The ontogeny of these antigens in mice was studied during sexual maturation. These antigens could be detected in cauda epididymis from day 50 onwards by immunohistochemistry. The highest concentration of these antigens was observed in the cauda epididymis of 80-day-old mice. SDS-PAGE analysis indicated that the 26 kd protein recognized by D2G4 was visible from day 50 onwards, confirming the immunohistochemical observations. The plasma testosterone levels showed a significant increase from days 40 to 60 followed by a decrease. The fact that these epididymal proteins appear during sexual maturation and at the time of the testosterone surge indicates that they are androgen dependent. PMID- 1918313 TI - Selection of an antibody-free population of spermatozoa from semen samples of men suffering from immunological infertility. AB - Ejaculates from infertile men with significant levels of antisperm antibodies were processed in vitro, in an attempt to prepare sub-populations of antibody free spermatozoa. Semen samples were processed on a discontinuous Percoll gradient and the resultant sperm preparation was treated with immunobeads. Selection of antibody-free spermatozoa was achieved: less than 10% of the resulting spermatozoa showed binding to immunobeads after treatment in all cases investigated. The overnight survival of these antibody-free spermatozoa was comparable to, or better than, that of the untreated antibody-coated sample obtained from the Percoll gradient. The fertility potential of these treated spermatozoa is currently under investigation. PMID- 1918315 TI - German Embryo Protection Act (October 24th, 1990): Gesetz zum Schutz von Embryonen (Embryonenschutzgesetz-ESchG). PMID- 1918314 TI - Hormonal dependence of pinopode formation at the uterine luminal surface. AB - The uterine luminal epithelium during the period of receptivity for nidation displays characteristic protrusions of the apical surface named pinopodes. The effects of oestradiol and progesterone, singly or in combination, on the formation and regression of pinopodes were investigated using scanning electron microscopy. The appearance of pinopodes was found to be strictly progesterone dependent. When given together with progesterone, before the development of pinopodes, high doses of oestradiol (plasma level approximately 300 pmol/l) inhibited pinopode formation; on the contrary, low doses of oestradiol (nidatory doses) did not interfere with the process until the 4th day of treatment. When oestradiol was given as a single injection, after pinopode formation, both doses were equivalent in inducing their regression 48-72 h later. It appears that the hormonal conditioning for pinopode formation and for the development of uterine receptivity for egg implantation is the same. These observations support the hypothesis that pinopodes could be an extremely useful tool to estimate uterine receptivity. The experiments we describe here, together with observations made a few years ago, in stimulated cycles in the human, suggest that implantation failure as a result of a hormonal imbalance during the time intervening between ovulation and nidation, may be a general phenomenon. PMID- 1918316 TI - Implications and consequences of the German Embryo Protection Act. PMID- 1918317 TI - Recurrent spontaneous abortion. PMID- 1918318 TI - The analysis of sperm motion with the Hamilton-Thorn motility analyser. PMID- 1918319 TI - Immune modulation within the brain: recruitment of inflammatory cells and increased major histocompatibility antigen expression following intracerebral injection of interferon-gamma. AB - Intracerebral injections of interferon-gamma (IFN-gamma) have multiple immunological effects on rat brain, affecting all anatomic compartments. Lymphocytes and other inflammatory cells are recruited to the injection site: CD4+ T-cells into the perivascular space, OX42+ monocytes/macrophages into brain parenchyma. IFN-gamma also recruits OX8+ cells into brain parenchyma. These OX8+ cells are not stained by 'pan' T-cell antibodies, however, suggesting that they may be natural killer cells. IFN-gamma also causes increased major histocompatibility complex expression on brain cells: class I antigen on local endothelial and ependymal cells, and class II antigen on microglial, ependymal, and perivascular cells throughout both hemispheres of the brain. PMID- 1918320 TI - Cyclophosphamide alters the clinical and pathological expression of experimental autoimmune gray matter disease. AB - Guinea pigs inoculated with bovine spinal cord ventral horn homogenate develop a syndrome termed experimental autoimmune gray matter disease (EAGMD) characterized by extremity weakness, bulbar signs, and a loss of lower and upper motoneurons. To provide evidence for the role of autoimmune mechanisms, we have administered the immunosuppressant cyclophosphamide prior to and after gray matter immunization. Pretreatment with cyclophosphamide prevented the appearance of clinical signs of disease and decreased the loss of spinal cord motoneurons, the appearance of damaged motoneurons, and the antibody titer to motoneurons. Treatment 7 days after immunization attenuated the expression of disease. Treatment immediately after signs also improved the clinical and pathological findings. In all cyclophosphamide-treated animals there was less IgG within motoneurons and less inflammation. These results support the role for autoimmune mechanisms in motoneuron loss and degeneration in EAGMD. PMID- 1918321 TI - Naturally occurring antibodies against nerve growth factor in human and rabbit sera: comparison between control and herpes simplex virus-infected patients. AB - Antibodies against nerve growth factor (NGF) in sera were detected by enzyme linked immunosorbent assays (ELISA), by their isolation after passage of sera through NGF immunoadsorbent columns and by their specificity to bind and immunoprecipitate mouse NGF as well as to stain by immunohistochemical methods cellular sites of NGF synthesis. Increased levels of anti-NGF antibodies were found in sera of herpes simplex virus (HSV)-infected patients but not in HSV inoculated rabbits. As HSV latency is known to be promoted by NGF in vitro, these results may suggest that anti-NGF antibodies modulate the cytokine function of NGF and thus might play a role in HSV infection. The biological function of circulating antibodies against NGF, in general, is now open to future investigation. PMID- 1918322 TI - Human tumor necrosis factor-alpha augments experimental allergic encephalomyelitis in rats. AB - The effect of human recombinant tumor necrosis factor-alpha (TNF) on experimental allergic encephalomyelitis (EAE) was studied in Lewis rats. TNF was injected intraperitoneally at a daily dose of 1 x 10(3) or 2 x 10(4) U for 8 consecutive days from one day after sensitization with guinea-pig spinal cord in complete Freund's adjuvant. All rats in the control group developed clinical signs of EAE but recovered within 8 days after the onset. Injections of 2 x 10(4) U/day of TNF resulted in a significant prolongation of clinical EAE: clinical signs were sustained for up to 15 days after onset. Histologically, rats receiving 2 x 10(4) U/day of TNF had more severe cellular infiltrations in the spinal cord than controls. The augmentation of EAE was not found in rats receiving 1 x 10(3) U/day of TNF or TNF that had been neutralized with anti-TNF monoclonal antibody. PMID- 1918323 TI - The parasympathetic nervous system takes part in the immuno-neuroendocrine dialogue. AB - In a series of experiments the communication between the parasympathetic nervous system and the immune system was examined in rats. The data are summarized as follows: (1) In vivo administration of physostigmine increased the number of plaque-forming cells whereas in vitro addition of cholinergic agonists decreased the specific antibody response. (2) Prolonged in vivo treatment with atropine or physostigmine influenced concanavalin A stimulation of lymphocytes of different compartments in different ways. (3) Immunization with sheep red blood cells changed the number and the affinity of muscarinic cholinergic receptors in the hippocampus. (4) Cholinergic stimulation in vivo inhibited the transient increase of plasma corticosterone following immunization. Our results provide evidence that the parasympathetic nervous system is included in the dialogue between the neuro-endocrine and the immune systems. PMID- 1918324 TI - Immunoblot for densitometric estimation of antibodies (IDEA): a useful method for quantification of intrathecally produced antibodies against individual antigens in infectious diseases of the central nervous system. AB - Intrathecally produced antibodies specific for the infectious agent can be shown by immunoblot. A quantification is practicable by titration. Densitometric evaluation of the immunoblot by a new technique, IDEA (immunoblot for densitometric estimation of antibodies), does not only render titration unnecessary, but also has the advantage of presenting the differentiated local immune response against individual antigens of the infectious agent. Preliminary studies for the densitometric evaluation were performed with a measles virus immunoblot which had been developed with a cerebrospinal fluid (CSF) sample of a patient suffering from multiple sclerosis containing high antibody titers. A peroxidase-labeled anti-immunoglobulin antibody had been added. The intensity of the color reaction on the membrane dependent on the antibody concentration follows a saturation kinetics comparable to the Michaelis-Menten kinetics in enzymology. Thus, indices for the intrathecal antibody synthesis of each individual viral antigen can be calculated by taking the permeability of the blood-CSF barrier into consideration. This method is illustrated in a patient with zoster meningoencephalitis. PMID- 1918325 TI - Activated T lymphocyte subsets in experimental allergic neuritis. AB - Changes in activated T cell subsets in peripheral blood were examined during the course of experimental allergic neuritis (EAN), using two-color immunofluorescence flow cytometry. Both CD4+ and CD8+ activated T cells decreased transiently before the onset of clinical signs, and increased just around the time of onset of the disease. In contrast, during the recovery phase, the numbers of CD4+ activated T cells returned to the normal range, whereas CD8+ activated T cells continued to increase. These findings imply that activation of CD4+ helper/inducer cells contributes mainly to the evolution of EAN, and that of CD8+ suppressor cells are necessary for recovery. PMID- 1918326 TI - Enhanced interferon-gamma-induced Ia-antigen expression by glial cells after previous exposure to this cytokine. AB - Encephalitogenic T cells appear capable of destroying class II major histocompatibility complex (MHC) antigen (Ia)-positive glial cells in the brain, thus accounting for the pathologic activity of these lymphocytes in experimental autoimmune encephalomyelitis (EAE). However, glial cells do not generally express Ia molecules, suggesting that regulation of Ia expression figures prominently in autoimmune diseases of the central nervous system. In studies to understand the regulatory mechanisms involved in Ia expression, a glial cell clone generated from the brains of neonatal Lewis rats (F10 clone) readily expressed class II major histocompatibility (Ia) antigens after stimulation by interferon-gamma (IFN gamma) at doses from 10 to 100 units/ml. Level of the antigen decreased gradually within 5-7 days after cultures were depleted of the cytokine. Reexposure of the cells to the IFN-gamma at 100-fold lower doses induced a stronger Ia response than did the initial exposure. F10 cells also expressed Ia when they were cultured with small numbers of syngeneic T lymphocytes, either proliferating or nonproliferating. Proliferating T cells had direct Ia-inducing activity, whereas nonproliferating T cells had this effect only when they were added to cultures with small amounts of T cell-specific antigen. Moreover, Ia-inducing effects of IFN-gamma on F10 cells were also greatly enhanced when these cells were preexposured to T cells. Our results suggest that initial exposure to IFN-gamma or T cells enhances the Ia responsiveness of glial cells to further stimulation with the cytokine. PMID- 1918327 TI - HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France. AB - The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrenees Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis. PMID- 1918328 TI - Antibodies to brain tissue in sera of patients with chronic progressive multiple sclerosis. AB - Using a blind indirect immunofluorescence assay we examined the sera of 30 multiple sclerosis (MS) patients and 30 age- and sex-matched controls for autoantibodies to brain tissue. Binding was found in 33% of the patients' sera and in only 3% of the controls' sera. Positive and negative patients differed significantly in the course of MS, since eight of the ten positive patients showed a chronic progressive form. None of the patients with a large deficit in a chronic state showed antibodies to brain tissue, while eight of the 11 active chronic progressive cases were positive. Therefore it seems possible that these brain antibodies could be used as an activity parameter, at least for this form of the disease. PMID- 1918330 TI - Effects of dexamethasone on microglial activation in vivo: selective downregulation of major histocompatibility complex class II expression in regenerating facial nucleus. AB - Following axotomy of the facial nerve microglial cells in the facial nucleus become activated, proliferate, and newly express class I and class II major histocompatibility complex (MHC) antigens. Dexamethasone treatment, starting 2 days prior to axotomy at 1 mg/kg/day, selectively inhibited axotomy-induced MHC class II expression on microglial and perivascular cells. In contrast, MHC class I expression was not significantly affected, nor was the expression of other microglial activation markers and the light microscopic morphology of activated microglia. A recently suggested inducer of MHC expression in rat nervous tissue, neuronal gamma interferon-like immunoreactive material, was also unaffected, as was glial fibrillary acidic protein immunoreactivity as a marker for concomitant astroglial activation. The differential effects of the drug suggest the presence of distinct regulatory pathways for different aspects of microglial activation. Inhibition of class II expression on activated microglia might be one mechanism how glucocorticoids act in the suppression of neuroinflammatory disease. PMID- 1918329 TI - The effects of exposure to dietary nickel and zinc upon humoral and cellular immunity in SJL mice. AB - We are interested in potential interactions between environmental trace metal exposures and immune function. In particular, we have wondered whether dietary exposure to nickel and zinc cations can influence T and B cell proliferation and function. To study this question, we fed SJL female mice supplemental nickel and zinc sulfate from 4-8 weeks of age, and immunized the animals intraperitoneally (i.p.) with keyhole limpet hemocyanin (KLH) at 8 weeks. Eight days later, we measured antibody responses to KLH. Both IgG and IgM antibody responses to KLH were significantly depressed in vivo in the nickel fed animals (p less than 0.005). In vitro antigenic responsiveness to KLH of splenocytes from nickel fed animals was also depressed compared with control and zinc supplemented animals (p less than 0.002). This altered antigenic responsiveness persisted even after cells had been cultured for 5 days in standard media. The zinc supplemented diets did not seem to affect antibody responsiveness and proliferation. The proliferative responses of B cells to the mitogen lipopolysaccharide (LPS) were significantly depressed in Ni fed mice, but were not affected in the zinc fed animals. T cell mitogenic responses to concanavalin A were not affected in the nickel fed animals, and were enhanced in zinc fed animals. We conclude that dietary exposure to certain trace metals may induce persisting alterations in immunity in this animal model. PMID- 1918331 TI - EEG and clinical neurophysiology at the Neurological Institute of New York. PMID- 1918332 TI - Progressive myoclonus epilepsies: clinical and neurophysiological diagnosis. AB - Diagnosis and management of the progressive myoclonus epilepsies (PMEs) provides a challenge to the clinician and neurophysiologist. Over 15 specific disorders can cause the PME syndrome; all are rare, and individual physicians are unlikely to have experience in all of them. Accurate diagnosis is essential to provide a prognosis, optimal therapy, and genetic counseling. The major causes are PME of the Unverricht-Lundborg type, Lafora disease, neuronal ceroid lipofuscinoses (three forms), MERRF (myoclonus epilepsy and ragged red fibers), and sialidoses (two forms), in addition to a number of even rarer disorders. Here we review the clinical aspects and neurophysiology of these disorders, which can now be diagnosed in life by relatively simple methods in the vast majority of cases. PMID- 1918333 TI - The benign partial nonrolandic epilepsies. AB - Although rolandic epilepsy is the only epileptic syndrome that, at present, fully meets all the criteria of benignity and is widely recognized as such, there are also other forms of partial epilepsy that are benign. These are also genetically determined and age-dependent, occurring in neurologically intact children older than 18 months of age. As a rule, the seizures are brief and infrequent, usually responding well to antiepileptic drugs and remitting spontaneously before adulthood. The EEG background is normal, the morphology of the spikes is typical, and they are activated by sleep; generalized spike-wave discharges may occur. During the past decade, there have been reports of a number of additional syndromes of benign partial epilepsy. These include benign occipital epilepsy (the most common in this group), benign frontal epilepsy, benign epilepsy with affective symptomatology (or benign psychomotor epilepsy), benign epilepsy with extreme somatosensory evoked potentials, benign partial epilepsy of adolescence, and benign epilepsy associated with multiple spike foci. The Landau-Kleffner syndrome is often included among the benign epilepsies. These nonrolandic benign epilepsies are described in detail, and the relevant literature is reviewed. PMID- 1918334 TI - Acquired epileptiform aphasia in children (Landau-Kleffner syndrome). AB - The association of a language disorder with epilepsy is frequent in children, but there is usually no causal relationship. In acquired epileptiform aphasia (AEA), the so-called Landau-Kleffner syndrome, there is increasing evidence that the language disorder is directly caused by epileptic discharges in critical language areas and must be viewed as a special kind of epileptic aphasia. This is based on a review of the published cases of AEA over the last 30 years and on the analogies that can be made between AEA and other epileptic syndromes, mainly benign partial epilepsy with centrotemporal spikes. AEA can start early in development and present as developmental dysphasia. It is only one among other cognitive or behavioral disturbances that can be epileptic manifestations of some particular epileptic syndromes, for example, epilepsy with continuous spike waves during slow sleep, which probably has the same pathophysiology as AEA. AEA must be seen, at least in some cases, as a particular form of resistant epilepsy. AEA is an important model because it suggests that isolated cognitive and behavioral disturbances can be epileptic manifestations in children. PMID- 1918335 TI - Electrical status epilepticus during slow-wave sleep: a review. AB - Electrical status epilepticus during sleep (ESES) is primarily an EEG-defined syndrome in children characterized by the occurrence of continuous spike and slow waves during non-rapid-eye-movement (non-REM) sleep, the paroxysmal abnormalities being substantially less frequent during the awake state and REM sleep. Etiologically, cases can be divided into symptomatic and cryptogenic varieties. Partial motor seizures, frequently nocturnal, precede the emergence of ESES, whereas absence seizures often occur during the phase of ESES. The emergence of ESES is associated with neuropsychological regression. The characteristic electrographic pattern and epilepsy generally disappear during adolescence and are associated with an improvement in neuropsychological function. However, if the cases reported in the literature are representative, then there is a high probability of considerable residual dysfunction. A number of factors, broadly termed ascertainment biases, likely contribute to the paucity of reports from North America and the greater recognition of the syndrome in Europe and Japan. The current information on ESES is critiqued in this review. PMID- 1918336 TI - Variation in power spectral analysis of the EEG with gestational age. AB - Power spectral analysis (PSA) of the EEG was studied in healthy term and preterm neonates to establish the normal range with gestational age. Sixty healthy newborn infants from 26 to 41 weeks' gestation had PSA performed at 3 days of age. Five main frequency bands were studied: delta 1 (1 Hz or less), delta 2 (2-3 Hz), theta, alpha, and beta. A significant correlation was shown between absolute power in delta 1 and delta 2 with gestational age. Relative power of each frequency band, calculated as a percentage of the total power in each channel, also correlated with gestational age. A significant quadratic relationship between absolute power in the beta range and gestational age is described for the first time. PMID- 1918337 TI - Effects of age, gender, and stimulus side on scalp topography of somatosensory evoked potentials following median nerve stimulation. AB - This is the first study to evaluate the effects of age, gender, and stimulus side on scalp topography of somatosensory evoked potentials (SEPs) following stimulation of the median nerve by using computerized bit-mapped color images. Seventy-four normal subjects whose ages ranged from 7 to 88 years were studied, and Student's t test was performed on averaged mean maps and their standard deviations of each recognizable component by using the significance probability mapping method. Topographic maps of most components in aged subjects were significantly different from those in young subjects, mainly because of higher amplitudes of the components in the aged group. This difference was particularly significant for later components with the peak latencies of longer than 40 ms. Gender and stimulus side caused no significant differences in amplitude and topography of the components. Therefore, for clinical application of topographic maps of median nerve SEPs, a difference of gender and stimulus side could be disregarded, but it is necessary to consider the age effect. PMID- 1918339 TI - Technology and equipment review. Ambulatory cassette EEG systems. PMID- 1918338 TI - Topography of scalp-recorded motor potentials in human finger movements. AB - Four distinct negative events were identified in the averaged, scalp-recorded EEGs of normal subjects before and after the onset of self-paced, voluntary finger movements; reaction-time movements and passive movements were also studied. These events are the peak of the negative slope (NS'), the initial slope of motor potential (isMP), the parietal peak of motor potential (ppMP), and the frontal peak of motor potential (fpMP). For self-paced movements, NS' and isMP occurred before the onset of electromyographic (EMG) activity, and ppMP and fpMP occurred after the onset of EMG activity. NS' had a wide distribution, covering the parietal region with slight contralateral predominance. The isMP mapped focally over the contralateral hand motor area on the scalp. The location of ppMP was similar to that of isMP. The fpMP was localized anterior and medial to motor cortex with a contralateral preponderance and possible location over the supplementary motor area. The isMP and fpMP also were identified in the recordings of reaction-time movements, but only the fpMP persisted in the recordings of passive movements. The isMP appears to reflect activation of the cortical cells in the hand area of motor cortex for the execution of voluntary movement, and the fpMP appears to reflect proprioceptive feedback from the periphery. PMID- 1918340 TI - Soft tissue anatomy of proximal femoral focal deficiency. AB - The soft tissue anatomy of Aitken types A, B, C, and D proximal femoral focal deficiency (PFFD) was examined by magnetic resonance imaging (MRI). A characteristic pattern of soft tissue abnormalities is described. All muscles were present, but most were smaller than their normal counterparts. The exception was the obturator externus muscle, which was elongated and remained muscular almost up to its insertion. In type A PFFD, it is straight; in types B, C, and D PFFD, it is L-shaped. The sartorius is hypertrophied. PMID- 1918341 TI - The energy expenditure index: a method to quantitate and compare walking energy expenditure for children and adolescents. AB - We used heart rate and walking speed to calculate an energy expenditure index (EEI), the ratio of heart rate per meter walked, for 102 normal subjects, age 6 18 years. Heart rate was measured at self-selected slow, comfortable, and fast walking speeds on the floor and on a motor-driven treadmill. At slow walking speeds (37 +/- 10 m/min) the EEI was elevated (0.71 +/- 0.32 beats/m), indicating poor economy. At comfortable speeds (70 +/- 11 m/min) the EEI values decreased to the maximum economy (0.47 +/- 0.13 beats/m). At fast speeds (101 +/- 13 m/min), the EEI increased (0.61 +/- 0.17 beats/m), indicating poor economy relative to comfortable speeds. A graph of the EEI versus walking speed provides a way to evaluate and compare energy expenditure in a clinical setting. PMID- 1918343 TI - Effects of lateral rotation splinting on lower extremity bone growth: an in vivo study in rabbits. AB - To study the effect of lateral splinting on limb development, 14 immature rabbit femurs and tibias were marked with six parallel pins. Of these, the lower limbs of seven rabbits were splinted in lateral rotation for 3 weeks (1-year human equivalent). The static position of the foot in the splinted group was 23 degrees more lateral (p greater than 0.05) than in the control group. No significant difference was found in the axial alignment of the pins across the growth plate or diaphyses between the splinted or control groups. This study suggests that night splinting alters the joint relationships and not the shape of the femur or tibia. PMID- 1918342 TI - Community ambulation by children with myelomeningocele and high-level paralysis. AB - It has frequently been noted that high-level paralysis precludes community ambulation for children with myelomeningocele. Of the 87 children in our population with high-level paralysis, however, 45 (52%) did achieve community ambulation by 5 years of age, while 42 (48%) did not. There was no significant difference between these two groups by sex, shunt status, scoliosis, or hip surgery prior to 5 years of age. Among the community ambulating group, there were significantly (p less than 0.001) more children who were not retarded, had received physical therapy for walking, and had compliant parents. We concluded, therefore, that community ambulation is a realistic goal for many children with myelomeningocele and high-level paralysis. PMID- 1918344 TI - Nontraumatic, acute neonatal paraplegia. AB - Nontraumatic, acute neonatal paraplegia with associated lower limb vascular phenomena is a relatively rare condition. Three such cases are reported. The paralysis is primarily motor with minimal neurologic recovery. Contractures and bizarre deformities develop at an early stage and necessitate repeated orthopaedic intervention. The most likely etiology appears to be a vascular insult to the spinal cord. PMID- 1918345 TI - Thoracic lordosis in idiopathic scoliosis. AB - Lordosis, a significant aspect of thoracic scoliosis, is difficult to assess with routine clinical radiographs. Computerized analysis of 138 sets of standardized anteroposterior and lateral radiographs served to elicit the three-dimensional structure of scoliosis. Spinal curvatures in the usual anatomic planes and in the sagittal and frontal planes of the apical vertebrae were measured. Lordosis was present in 35% of curves greater than or equal to 40 degrees and in 50% of curves greater than 49 degrees. Lordosis may be a contraindication for brace treatment. PMID- 1918346 TI - Vertebral abnormalities associated with congenital sacrococcygeal teratomas. AB - An orthopedic and radiologic follow-up study was performed on 45 patients who had undergone surgery for a benign congenital sacrococcygeal teratoma (SCT). Eighty percent of the patients had one to three vertebral abnormalities at the mean age of 21 years. Extrapelvic primary tumors were associated with subsequent development of spondylolysis in the lumbosacral spine, and intrapelvic primary tumors were associated with multiple spina bifida occulta lesions and other spinal anomalies. In addition, an increased incidence of congenital dislocation of the hip (7%) was observed in patients with SCTs. PMID- 1918347 TI - Ultrasound in the diagnosis and follow-up of transient synovitis of the hip. AB - Of 59 patients (2-15 years of age) with acute synovitis of the hip, one patient developed Perthes disease (1.7%) and the others transient synovitis. The diagnostic criterion for intracapsular effusion was a side difference greater than or equal to 2.0 mm in the distance between the anterior joint capsule and the femoral neck (anterior capsule distance, ACD). At the time of admission, the mean ACD of the affected and unaffected hips was 8.2 and 4.2 mm, respectively. The effusion persisted for greater than 1 week in 58% of the patients. We recommend ultrasound as the main imaging technique in the diagnosis and follow-up of transient synovitis. Radiography may be omitted in uncomplicated cases, but should be employed when Perthes disease is suspected. PMID- 1918348 TI - Congenital hip dislocation or dysplasia with subluxation: a radiologic study. AB - We studied the behavior of hips in congenital hip dislocation. Two types were identified: those that developed normally after closed reduction and those that required an osteotomy. Children with hips that required an osteotomy were older at presentation and at follow-up had worse subluxation, with shallower acetabula. In this group, the younger the age at which reduction was achieved, the less the residual subluxation of the hip at follow-up. The age at which the late osteotomy was performed did not appear to affect the residual hip subluxation or the acetabular development. We could not find any radiologic parameter that would predict the need for an osteotomy. PMID- 1918349 TI - Magnetic resonance imaging in congenital dysplasia of the hip. AB - This study was designed to determine the usefulness of magnetic resonance imaging (MRI) in managing congenital hip dysplasia and dislocation. We compared various hip parameters using bony and cartilaginous landmarks. MRI determined that the bony acetabular index (AI) accurately reflects the cartilaginous AI. Bony acetabular indices greater than 30 degrees indicated hip dysplasia, subluxation, or dislocation. MRI demonstrates qualitative information not available on plain films; however, it does not provide further quantitative data, so we do not recommend its routine use in the evaluation of congenital hip dysplasia. The true benefit of MRI may be its ability to identify a group of patients with bone dysplasia but normal cartilaginous growth potential. PMID- 1918350 TI - Cartilage necrosis due to pin penetration: experimental studies in rabbits. AB - An animal model was used to evaluate the role of pin penetration into the hip joint as the cause of chondrolysis. The gross and microscopic studies, as well as the biochemical studies, showed changes indicating cartilage destruction. These changes were more severe when the pins remained in the joint. Immunologic studies showed some type of immunological interaction. The immunologic response may be initiated by release of cartilage byproducts. The initial insult of the slip may cause release of cartilage byproducts from the exposed growth plate within the joint, and is compounded by penetration of the pin in the hip joint. PMID- 1918352 TI - Osteochondral fractures of the glenoid fossa of the ulna in children: review of four cases. AB - Osteochondral fractures of the glenoid fossa of the ulna are exceptional injuries in children. These lesions can present diagnostic problems because the fragments are often radiolucent. We followed four children for 3, 6, and 24 months and 12 years, respectively. The elbow was definitely dislocated in two, and was probably dislocated in two other, children. The most reliable paraclinical examination was conventional sagittal tomography. Open revision is mandatory for reduction of the fracture and, when performed early, may lead to excellent functional results. PMID- 1918351 TI - Growth disturbances of the proximal femur after pinning of juvenile slipped capital femoral epiphysis. AB - Premature closure of the capital femoral physis after pin fixation of slipped capital femoral epiphysis (SCFE) in the juvenile population (at least 1 year less than the established mean) can lead to growth disturbances of the proximal femur. A retrospective review of 21 patients (33 hips) who had a pinning of a juvenile SCFE was performed. Growth disturbances including greater trochanteric overgrowth, coxa vara, and coxa breva were noted in 64% of the hips. An 80% incidence of bilateral involvement was noted in the juvenile group. Consideration should be given to prophylactic pinning of the contralateral hip and use of a smooth pin construct to prevent premature closure of the growth plate in children with significant growth remaining. PMID- 1918353 TI - Surgical management of nerve injuries of the upper extremity in children: a 15 year survey. AB - In a 15-year retrospective study, the results of 37 surgically treated nerve lesions of the upper extremity in 33 children were reviewed after a mean follow up of 2 years. Children ranged in age from 4 to 15 years. There were 19 ulnar, 12 median, and 6 radial nerve injuries. Discontinuity of the nerve trunk was found in 23 patients operated by interfascicular grafting (18 patients) or epineural suture (5 patients). The other 14 lesions were treated by decompressive external neurolysis. Useful sensory function (S4-S3) assessed at the autonomous zone was restored in 31 patients (84%). Satisfactory motor recovery was achieved in 25 patients (67%). Independent of the type of lesion, the median nerve showed the best ability to regain complete motor and sensory function. In lesions with continuity of the nerve trunk, those affecting the radial nerve had a worse prognosis regarding motor function recovery. Unfavorable prognosis was mainly related to a time interval of more than 1 year between nerve damage and surgery. PMID- 1918354 TI - Proximal tibial extension medial rotation osteotomy to correct knee flexion contracture and lateral rotation deformity of tibia after polio. AB - A proximal tibial extension medial rotation osteotomy was performed on 17 tibias in postpoliomyelitis patients to correct knee flexion contractures simultaneously with the correction of lateral rotation deformity of the tibia through the same osteotomy. Gait improved in 10 patients. Five patients developed recurrence of knee flexion contractures; five more developed greater than 20 degrees genu recurvatum. One patient developed a common peroneal nerve palsy. Because of the high incidence of complications, we recommend that this procedure be abandoned. PMID- 1918355 TI - Tendoachilles tenodesis to the fibula: a retrospective study. AB - Tendoachilles tenodesis to the fibula was performed in postpolio patients to improve their gait. The charts of 48 patients with 52 tenodeses were reviewed. The mean follow-up was 5.5 years. Gait improved in one-third. When the hindfoot was stabilized, gait improved in 40% of the patients, but when it was not stabilized, only 22% improved their gait. Excessive equinus developed in 18 patients, all of whom were less than age 12 years when operated. We conclude that it is reasonable to use this procedure to improve the gait of postpolio children with flail lower extremity, provided the hindfoot is stabilized. PMID- 1918356 TI - Pseudoaneurysm after foot surgery. AB - Pseudoaneurysm (PA) is recognized as a rare complication after pediatric foot surgery. We identified the incidence, pertinent clinical features, and response to surgical intervention in PA as a complication of foot surgery. Four PAs were identified after 2,756 foot operations, an overall incidence of 0.14%. These patients typically had symptoms between 2 and 3 months after index operation with an enlarging, pulsatile, compressible mass in the plantar medial aspect of the foot. Arteriography was helpful in planning surgical intervention. Operative treatment consisted of ligation and excision of PA in all patients. Final outcome of foot deformity surgery was not compromised. PMID- 1918357 TI - Acute cholecystitis after spinal fusion and instrumentation in children. AB - Three children developed noncalculus cholecystitis after spinal fusion and instrumentation for their spinal deformity. Two children responded to conservative therapy, and one required cholecystectomy. If diagnosed early, this complication may be successfully treated by conservative means. PMID- 1918358 TI - Congenital absence of the lumbar spine and sacrum: one-stage reconstruction with subsequent two-stage spine lengthening. AB - This is a case report of a child born with severe, type IV lumbosacral agenesis. At age 6 years, she had surgical reconstruction of her absent spine and thoracic pelvic instability with Harrington rods and autogenous bone obtained from simultaneous bilateral knee disarticulations. This arthrodesis healed solidly, and at the age of 10 years 6 months and again at age 12 years 6 months, she underwent spine lengthening by osteotomy and distraction instrumentation, the first time with Moe rods and the second time with Cotrel-Dubousset rods. Both lengthening osteotomies healed without difficulty. The spine lengthening achieved was 5.0 cm. PMID- 1918359 TI - Paraxial macrodystrophia lipomatosa of the medial right lower limb. AB - We report the orthopaedic management of a child with macrodystrophia lipomatosa of the medial aspect of the right lower limb. Bony and soft tissue overgrowth of the medial aspect of the lower limb resulted in valgus deformities at the subtalar joint, ankle, knee, and hip. The paraxial distribution, which has not been previously reported, suggests that the condition may be caused by alteration of somatic cells during limb bud development. PMID- 1918360 TI - Premature closure of the triradiate cartilage: a potential complication of pericapsular acetabuloplasty. AB - A case of premature triradiate cartilage closure secondary to a Gill acetabuloplasty performed at age 14 months is reported. The deficiency in acetabular development and failure of the pelvis to grow to its anticipated height is documented. A proximal femoral redirectional osteotomy and an innominate osteotomy performed near maturity improved femoral head coverage and hip biomechanics. Acetabuloplasties performed adjacent to the triradiate cartilage typically do not have any adverse effect on its function. Despite this low risk of injury to the triradiate cartilage after a Gill or Pemberton acetabuloplasty, long-term follow-up is recommended to observe acetabular development. Premature closure is most likely to occur if the bone graft used to maintain fragment displacement crosses the triradiate cartilage. PMID- 1918361 TI - Simple method of documenting metatarsus adductus. AB - A simple, accurate, and inexpensive method of documenting metatarsus adductus involves taking photocopies of the foot in the weightbearing position. Subsequently, treatment progress can be assessed objectively by reviewing serial photocopies. Some caution is urged because the strength of the glass copying surface of photocopying machines is unknown. PMID- 1918362 TI - Measuring outcomes in cerebral palsy. PMID- 1918363 TI - In search of Mr. Wizard. Presidential Address to the American Society for Clinical Investigation, Seattle, Washington, 4 May 1991. PMID- 1918364 TI - Differential protease expression by cutaneous squamous and basal cell carcinomas. AB - To assess the postulated role of plasminogen activation in tumor invasion, we have investigated the cellular sites of synthesis for urokinase-type (uPA) and tissue-type (tPA) plasminogen activators and their inhibitors (PAI-1 and PAI-2) in two human cutaneous neoplasia that differ in their metastatic potential. The combined use of zymography on tissue sections and in situ hybridization demonstrates that uPA is produced by malignant cells of squamous cell carcinomas (SCC) but not by basal cell carcinomas (BCC), whereas tPA is detected exclusively in nonmalignant dermal tissue. In addition, we show that SCC neoplastic cells simultaneously produce variable amounts of PAI-1, and that PAI-1 production correlates inversely with uPA enzymatic activity. These observations establish that invasive human malignant cells in vivo can activate plasminogen through uPA production during the early phases of tumor growth; they also demonstrate that the proteolytic activity of tumor cells can be modulated by the concomitant production of PAI-1. Because SCC have a higher invasive and metastatic potential than BCC, our findings lend further support to the involvement of plasminogen activation in malignant behavior. PMID- 1918365 TI - Killing of gram-negative bacteria by lactoferrin and lysozyme. AB - Although lactoferrin has antimicrobial activity, its mechanism of action is not full defined. Recently we have shown that the protein alters the Gram-negative outer membrane. As this membrane protects Gram-negative cells from lysozyme, we have studied whether lactoferrin's membrane effect could enhance the antibacterial activity of lysozyme. We have found that while each protein alone is bacteriostatic, together they can be bactericidal for strains of V. cholerae, S. typhimurium, and E. coli. The bactericidal effect is dose dependent, blocked by iron saturation of lactoferrin, and inhibited by high calcium levels, although lactoferrin does not chelate calcium. Using differing media, the effect of lactoferrin and lysozyme can be partially or completely inhibited; the degree of inhibition correlating with media osmolarity. Transmission electron microscopy shows that E. coli cells exposed to lactoferrin and lysozyme at 40 mOsm become enlarged and hypodense, suggesting killing through osmotic damage. Dialysis chamber studies indicate that bacterial killing requires direct contact with lactoferrin, and work with purified LPS suggests that this relates to direct LPS binding by the protein. As lactoferrin and lysozyme are present together in high levels in mucosal secretions and neutrophil granules, it is probable that their interaction contributes to host defense. PMID- 1918366 TI - Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon gamma-activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophila. AB - We have been exploring the role of iron in the pathogenesis of the intracellular bacterial pathogen Legionella pneumophila. In previous studies, we have demonstrated that L. pneumophila intracellular multiplication in human monocytes is iron dependent and that IFN gamma-activated monocytes inhibit L. pneumophila intracellular multiplication by limiting the availability of iron. In this study, we have investigated the effect on L. pneumophila intracellular multiplication of lactoferrin, an iron-binding protein which is internalized via specific receptors on monocytes, and of nonphysiologic iron chelates which enter monocytes by a receptor-independent route. Apolactoferrin completely inhibited L. pneumophila multiplication in nonactivated monocytes, and enhanced the capacity of IFN gamma activated monocytes to inhibit L. pneumophila intracellular multiplication. In contrast, iron-saturated lactoferrin had no effect on the already rapid rate of L. pneumophila multiplication in nonactivated monocytes. Moreover, it reversed the capacity of activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron from the lactoferrin-lactoferrin receptor pathway. The capacity of iron-lactoferrin to reverse monocyte activation was dependent upon its percent iron saturation and not just its total iron content. Similarly, the nonphysiologic iron chelates ferric nitrilotriacetate and ferric ammonium citrate completely reverse and ferric pyrophosphate partially reversed the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron derived from nonphysiologic iron chelates internalized by monocytes independently of the transferrin and lactoferrin endocytic pathways. This study suggests that at sites of inflammation, lactoferrin may inhibit or promote L. pneumophila intracellular multiplication in mononuclear phagocytes depending upon its degree of iron saturation. In addition, this study suggests a potential role for PMN in host defense against L. pneumophila--providing apolactoferrin to infected monocytes--and it supports the concept that PMN and monocytes may cooperate in host defense against intracellular parasites and other pathogens. PMID- 1918368 TI - A pH modifier site regulates activity of the Na+:HCO3- cotransporter in basolateral membranes of kidney proximal tubules. AB - HCO3- exit across the basolateral membrane of the kidney proximal tubule cell is mediated via an electrogenic Na+:HCO3- cotransporter. In these experiments, we have studied the effect of internal pH on the activity of the Na+:HCO3- cotransport system in basolateral membrane vesicles isolated from rabbit renal cortex. Equilibrium thermodynamics predicts that in the presence of constant intravesicular concentration of Na+, an increasing concentration of HCO3- will be associated with an increasing driving force for Na+:HCO3- cotransport across the vesicles. Our experimental approach was to preequilibrate the membrane vesicles with 1 mM 22Na+ at pHi 6.8-8.0 and known concentrations of HCO3-. The vesicles were diluted 1:100 into Na(+)-free solution at pH 7.4 and the net flux of 22Na+ was assayed over 5 s. The results demonstrate that the net flux of Na+ was significantly higher at pHi 7.2 than pHi 8.0 despite much higher [HCO3-] at pHi 8.0. This suggests that an internal pH-sensitive site regulates the activity of the Na+:HCO3- cotransporter. This modifier site inhibits the cotransporter at alkaline pH despite significant base concentration and is maximally functional around physiologic pH. The combination of modifier sites on the luminal Na+/H+ exchanger and the basolateral Na+:HCO3- cotransporter should help maintain intracellular pH in a narrow range with changes in extracellular pH. PMID- 1918367 TI - Ligand bridging mediates integrin alpha IIb beta 3 (platelet GPIIB-IIIA) dependent homotypic and heterotypic cell-cell interactions. AB - The aggregation of cells bearing recombinant integrin alpha IIb beta 3 (platelet GPIIb-IIIa) has been analyzed by two-color flow cytometry. As in normal platelets, aggregation requires functional alpha IIb beta 3, "activation" of alpha IIb beta 3, and fibrinogen (fg) binding to alpha IIb beta 3. Cellular aggregation required that both interacting cells express functional alpha IIb beta 3, because a binding defective mutant, alpha IIb beta 3 (D119----Y), failed to support interaction with wild type alpha IIb beta 3-bearing cells. In addition, cells bearing resting alpha IIb beta 3 were incorporated into aggregates formed by cells bearing a constitutively active mutant, alpha IIb beta 3 (beta 1-2), indicating that only one of the cells in an interacting pair must be activated. Finally, heterotypic interactions occurred between cells bearing activated alpha IIb beta 3 and cells bearing alpha V beta 3, a fg-binding integrin present on endothelial and tumor cells. Thus, ligand bridging between fg binding integrins represents a mechanism of cell-cell interaction, cells bearing resting alpha IIb beta 3 (e.g., resting platelets) may be incorporated into aggregates formed by cells bearing activated alpha IIb beta 3, and alpha IIb beta 3 mediates heterotypic interactions with cells bearing other fg receptors. PMID- 1918369 TI - Alteration of collagen phenotypes in ischemic cardiomyopathy. AB - Ischemic cardiomyopathy refers to a significant impairment of left ventricular function, a condition resulting from atherosclerotic coronary artery disease. The left ventricular ejection fraction is usually 35% or less, and electron microscopy shows an increased deposition of collagen in the space between the capillaries and the myocytes. The present study shows the alteration in collagen concentration and phenotypes in ischemic cardiomyopathy, and the effect captopril treatment has on these parameters. In patients with ischemic cardiomyopathy, collagen concentration estimated from hydroxyproline increased from 7.96 +/- 1.24 mg/g to 13.9 +/- 1.30 mg/g, P less than 0.05. Ischemic cardiomyopathic patients given captopril therapy had a significantly lower collagen concentration of 10.03 +/- 1.46 mg/g, P less than 0.05. The collagen type I:III ratio decreased from 1.93 +/- 0.52 to 1.23 +/- 0.27 in patients with ischemic cardiomyopathy. Of these patients, those receiving captopril had a collagen type I:III ratio of 1.49 +/- 0.38, which did not differ significantly from the ratio of individuals with normal myocardium. There was no significant difference in type I collagen concentration in the myocardium of normal individuals, patients with ischemic cardiomyopathy, and patients with ischemic cardiomyopathy receiving captopril therapy. The type III collagen concentration increased significantly from 2.56 +/ 0.21 mg/g in normal myocardium to 6.10 +/- 0.58 mg/g in ischemic cardiomyopathic myocardium. Patients receiving captopril had a myocardial collagen type III concentration of 4.87 +/- 0.64 mg/g, which was significantly lower than that found in patients with ischemic cardiomyopathy. An increased deposition of type III collagen may be partly responsible for altering the compliance of the myocardium, resulting in dilatation of the heart and possibly leading to eventual heart failure. PMID- 1918371 TI - Decreased DNA synthesis by cultured osteoblastic cells in eugonadal osteoporotic men with defective bone formation. AB - To determine the osteoblastic dysfunction that may be involved in the pathophysiology of osteoporosis in men we have compared histomorphometric indices of bone formation with in vitro characteristics of osteoblastic cells isolated from the trabecular bone surface in 23 untreated men with eugonadal osteoporosis. In most patients (n = 14), trabecular bone loss resulted from decreased bone formation evidenced by a lower than normal osteoblast surface, double tetracycline labeled surface, bone formation rate, and mean wall thickness. In these patients, DNA synthesis by cultured osteoblastic cells was altered. The peak of [3H]thymidine incorporation into DNA, the maximal DNA synthesis, and the area under the curve of cell proliferation were lower than the values in normal bone cells from age-matched controls. Parameters of bone cell growth were decreased in correlation with the extent of actively bone forming surfaces. By contrast, in patients (n = 9) with normal histomorphometric indices of bone formation, bone cell proliferation in vitro was not different from normal. Parameters of osteoblastic differentiation in vitro such as osteocalcin production and alkaline phosphatase activity were normal in the two groups of patients. This study shows that the trabecular bone loss resulting from defective bone formation in eugonadal osteoporotic men is associated with a lower than normal proliferative capacity of osteoblastic cells lining the trabecular bone surface. PMID- 1918370 TI - Illegitimate transcription. Application to the analysis of truncated transcripts of the dystrophin gene in nonmuscle cultured cells from Duchenne and Becker patients. AB - We have previously demonstrated that there is a low level of transcription of tissue-specific genes in every cell type. In this study, we have taken advantage of this phenomenon, called illegitimate transcription, to analyze the muscle-type dystrophin mRNA in easily accessible cells such as lymphoid cells, fibroblasts, and peripheral blood cells from Duchenne and Becker muscular dystrophies with known internal gene deletion. The results showed that, in the studied regions surrounding the deletions, processing of truncated transcripts is identical in specific (muscle tissue) and in nonspecific cells (lymphoid cells). In Becker cases with out-of-frame deletions, the already described alternatively spliced species found in muscle samples were also found in nonspecific cells. These results demonstrate that illegitimate transcripts are a bona fide version of tissue-specific mRNA, and that they represent a useful material to investigate the qualitative consequences of gene defects at the mRNA level. PMID- 1918372 TI - Use of an anti-low density lipoprotein receptor antibody to quantify the role of the LDL receptor in the removal of chylomicron remnants in the mouse in vivo. AB - Lipoproteins are removed from the plasma by LDL receptor-dependent and independent pathways. The relative contribution of these has been established for LDL by using modified lipoproteins, but this has not been possible for apoE-rich lipoproteins, such as chylomicron remnants. To do this, we used a monospecific antibody to the rat LDL receptor. The antibody was injected intravenously into mice followed by 125I-lipoproteins. Blood samples were obtained sequentially and radioactivity measured to determine the plasma clearance of the lipoproteins. The animals were then sacrificed and the tissues removed, dried, and the radioactivity measured to determine tissue uptake. An albumin space was also measured to correct for blood trapping. With 125I-human LDL, approximately 50% of the injected dose was cleared in 180 min. This was reduced to 30% by the antibody and this was identical to the disappearance of reductively methylated LDL. This is a lower estimate of LDL-mediated uptake (40%) than in other species. LDL uptake per gram tissue was similar for the liver and the adrenal gland and was approximately 50% LDL receptor-dependent in both tissues. With 125I-chylomicron remnants, clearance was much more rapid with approximately 50% cleared in 5 min. By agarose gel electrophoresis, radioactivity was not transferred from chylomicron remnants to other lipoprotein classes. Chylomicron remnants with label on only apoB or in 3H-cholesterol esters showed a similar pattern. Combining the estimates of the three labeling procedures, approximately 35% of the 30 s and 25% of the 5 min chylomicron remnant disappearance was LDL receptor dependent. The liver, per gram tissue, took up five times as much radioactivity as the adrenal gland. At 5 min, at least 50% of this was LDL receptor-dependent in liver and 65% in adrenal gland. We conclude that the LDL receptor plays a major, and somewhat similar quantitative role in the clearance of both LDL and chylomicron remnants in the mouse. However, at least in the mouse, non-LDL receptor-mediated lipoprotein clearance is quantitatively important and is also very rapid for chylomicron remnants. Thus, for chylomicron remnants, it can easily compensate for LDL receptors if they are blocked or absent. Further, the tissue distribution of lipoprotein uptake may be directed by factors other than LDL receptor density. PMID- 1918373 TI - Fibronectin biosynthesis in the rat aorta in vitro. Changes due to experimental hypertension. AB - This study was undertaken to determine if changes in fibronectin biosynthesis accompany the phenotypic changes that occur in aortic tissue following experimental hypertension. An in vitro procedure was developed to measure fibronectin synthesis in aortic rings obtained from normotensive or hypertensive rats. There was a three to sixfold increase in fibronectin biosynthesis by aortic rings taken from rats treated with deoxycorticosterone/salt for 7 and 21 d, the change being more pronounced at 21 d. In contrast, there was no major change at either time point in net incorporation into total protein. Studies comparing fibronectin biosynthesis in aortic rings from Wistar rats and spontaneously hypertensive rats at ages between 10 and 40 wk showed increased fibronectin biosynthesis in older animals of both strains, but only slight differences between strains. Studies using rats infused with angiotensin II showed a correlation between blood pressure elevation and increased aortic fibronectin biosynthesis. Western blot analysis of aortic extracts showed that the fibronectin content was increased in the hypertensive models. The in vitro procedure for measuring fibronectin biosynthesis appears to provide a reliable reflection of in vivo changes in fibronectin expression, and the methodology could prove useful for studying the factors influencing protein expression in vascular tissue. PMID- 1918374 TI - Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect. AB - We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39 +/- 5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (VO2) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v O2 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7 +/- 2.1) despite normal oxygen carrying capacity and Hgb-O2 P50. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Qmax, patient = 303 ml/min per kg, normal men 238 +/- 36) and the slope of increase in Q relative to VO2 (i.e., delta Q/delta VO2) from rest to exercise was exaggerated (delta Q/delta VO2, patient = 29, normal men = 4.7 +/- 0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex II in skeletal muscle was confirmed by the finding of deficiency of succinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle. PMID- 1918375 TI - Alterations in the structure, physicochemical properties, and pH of hepatocyte lysosomes in experimental iron overload. AB - While hemochromatosis is characterized by sequestration of iron-protein complexes in hepatocyte lysosomes, little is known about the effects of excess iron on these organelles. Therefore, we studied the effects of experimental iron overload on hepatocyte lysosomal structure, physicochemical properties, and function in rats fed carbonyl iron. A sixfold increase (P less than 0.0001) in hepatic iron and a fivefold increase in lysosomal iron (P less than 0.01) was observed after iron loading; as a result, hepatocyte lysosomes became enlarged and misshapen. These lysosomes displayed increased (P less than 0.0001) fragility; moreover, the fluidity of lysosomal membranes isolated from livers of iron-loaded rats was decreased (P less than 0.0003) as measured by fluorescence polarization. Malondialdehyde, an end product of lipid peroxidation, was increased by 73% (P less than 0.008) in lysosomal membranes isolated from livers of iron-overloaded rats. While amounts of several individual fatty acids in isolated lysosomal membranes were altered after iron overload, cholesterol/phospholipid ratios, lipid/protein ratios, double-bond index, and total saturated and unsaturated fatty acids remained unchanged. The pH of lysosomes in hepatocytes isolated from livers of iron-loaded rats and measured by digitized video microscopy was increased (control, 4.70 +/- 0.05; iron overload, 5.21 +/- 0.10; P less than 0.01). Our results demonstrate that experimental iron overload causes marked alterations in hepatocyte lysosomal morphology, an increase in lysosomal membrane fragility, a decrease in lysosomal membrane fluidity, and an increase in intralysosomal pH. Iron-catalyzed lipid peroxidation is likely the mechanism of these structural, physicochemical, and functional disturbances. PMID- 1918376 TI - Staphylococci surviving intracellularly in phagocytes from patients suffering from chronic granulomatous disease are killed in vitro by antibiotics encapsulated in liposomes. AB - Granulocytes and monocytes/macrophages from patients suffering from chronic granulomatous disease (CGD) are ineffective in killing specific kinds of phagocytized bacteria, e.g., Staphylococcus aureus, due to decreased or lacking ability to produce reactive oxygen intermediates. Commonly used antibiotics like flucloxacillin are of limited therapeutic value, because the staphylococci are protected against their action in the interior of phagocytes. However, encapsulation of flucloxacillin into liposomes could enable its entrance into the interior of neutrophils from two CGD patients to kill phagocytized bacteria there. The effect of rifampicin against intracellular staphylococci could be similarly enhanced by liposome encapsulation. Dose-response relations and kinetics of killing of intracellular bacteria by antibiotics in the free and encapsulated form were studied under different conditions using J 774 mouse macrophages, because phagocytes from CGD patients are not available in great amounts. Preincubation of phagocytes with either antibiotic in liposomes subsequently endowed the cells with a strongly enhanced ability to kill phagocytized bacteria. Our data show that a drug which normally will not reach a phagosome can be delivered to this intracellular compartment by a liposome. A possible clinical use is discussed. PMID- 1918377 TI - Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport. AB - To study the route by which plasma insulin enters cerebrospinal fluid (CSF), the kinetics of uptake from plasma into cisternal CSF of both insulin and [14C]inulin were analyzed during intravenous infusion in anesthetized dogs. Four different mathematical models were used: three based on a two-compartment system (transport directly across the blood-CSF barrier by nonsaturable, saturable, or a combination of both mechanisms) and a fourth based on three compartments (uptake via an intermediate compartment). The kinetics of CSF uptake of [14C]inulin infused according to an "impulse" protocol were accurately accounted for only by the nonsaturable two-compartment model (determination coefficient [R2] = 0.879 +/ 0.044; mean +/- SEM; n = 5), consistent with uptake via diffusion across the blood-CSF barrier. When the same infusion protocol and model were used to analyze the kinetics of insulin uptake, the data fit (R2 = 0.671 +/- 0.037; n = 10) was significantly worse than that obtained with [14C]inulin (P = 0.02). Addition of a saturable component of uptake to the two-compartment model improved this fit, but was clearly inadequate for a subset of insulin infusion studies. In contrast, the three-compartment model accurately accounted for CSF insulin uptake in each study, regardless of infusion protocol (impulse infusion R2 = 0.947 +/- 0.026; n = 10; P less than 0.0001 vs. each two-compartment model; sustained infusion R2 = 0.981 +/- 0.003; n = 5). Thus, a model in which insulin passes through an intermediate compartment en route from plasma to CSF, as a part of a specialized transport system for the delivery of insulin to the brain, best accounts for the dynamics of this uptake process. This intermediate compartment could reside within the blood-CSF barrier or it may represent brain interstitial fluid, if CNS insulin uptake occurs preferentially across the blood-brain barrier. PMID- 1918378 TI - Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus. AB - Increased nonesterified fatty acid (NEFA) levels may be important in causing insulin resistance in skeletal muscles in patients with non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of the antilipolytic nicotinic acid analogue Acipimox (2 X 250 mg) on basal and insulin-stimulated (3 h, 40 mU/m2 per min) glucose metabolism was therefore studied in 12 patients with NIDDM. Whole body glucose metabolism was assessed using [3-3H]glucose and indirect calorimetry. Biopsies were taken from the vastus lateralis muscle during basal and insulin-stimulated steady-state periods. Acipimox reduced NEFA in the basal state and during insulin stimulation. Lipid oxidation was inhibited by Acipimox in all patients in the basal state (20 +/- 2 vs. 33 +/- 3 mg/m2 per min, P less than 0.01) and during insulin infusion (8 +/- 2 vs. 17 +/- 2 mg/m2 per min, P less than 0.01). Acipimox increased the insulin-stimulated glucose disposal rate (369 +/- 49 vs. 262 +/- 31 mg/m2 per min, P less than 0.01), whereas the glucose disposal rate was unaffected by Acipimox in the basal state. Acipimox increased glucose oxidation in the basal state (76 +/- 4 vs. 50 +/- 4 mg/m2 per min, P less than 0.01). During insulin infusion Acipimox increased both glucose oxidation (121 +/- 7 vs. 95 +/- 4 mg/m2 per min, P less than 0.01) and nonoxidative glucose disposal (248 +/- 47 vs. 167 +/- 29 mg/m2 per min, P less than 0.01). Acipimox enhanced basal and insulin-stimulated muscle fractional glycogen synthase activities (32 +/- 2 vs. 25 +/- 3%, P less than 0.05, and 50 +/- 5 vs. 41 +/- 4%, P less than 0.05). Activities of muscle pyruvate dehydrogenase and phosphofructokinase were unaffected by Acipimox. In conclusion, Acipimox acutely improved insulin action in patients with NIDDM by increasing both glucose oxidation and nonoxidative glucose disposal. This supports the hypothesis that elevated NEFA concentrations may be important for the insulin resistance in NIDDM. The mechanism responsible for the increased insulin-stimulated nonoxidative glucose disposal may be a stimulatory effect of Acipimox on glycogen synthase activity in skeletal muscles. PMID- 1918379 TI - Role of L-thyroxine in nuclear thyroid hormone receptor occupancy and growth hormone production in cultured GC cells. AB - The contribution of L-thyroxine (T4) to nuclear thyroid receptor occupancy was studied in GC cells incubated with concentrations of 3,5,3'-triiodo-L-thyronine (T3) and T4 that resulted in free iodothyronine levels similar to those in serum of euthyroid rats. T4 accounted for 5.4-10% of the occupied receptors: T3 derived from T4 [T3(T4)] and T3 added to medium accounted for the remainder of receptor occupancy. Incubation with increasing medium free T4 resulted in a progressive increase in the contribution of T4 and T3(T4) to receptor occupancy. In incubations with 3.6-fold increased medium free T4, T4 accounted for 20.4%, and T3(T4) for 40.3% of receptor occupancy. These occupancy data and the experimentally determined Ka of thyroid receptor for T3 and T4 allowed calculation of nuclear free iodothyronine concentrations. Nuclear free T3 was 3-6 fold greater than medium free T3 and nuclear [corrected] free T4 was 12-19-fold greater than medium free T4. When GC cells were incubated with decreased medium free T3 and physiological medium free T4, both nuclear receptor occupancy and growth hormone production decreased as well. However, a twofold increase in medium free T4, in the presence of decreased medium free T3, restored receptor occupancy and growth hormone production to or near control values. These findings establish a role for T4 in addition to T3(T4) in nuclear receptor occupancy and biological activity in rat anterior pituitary tissue both in physiologic conditions and when medium free T4 is raised. The findings may have relevance to the sick euthyroid thyroid syndrome in which free T4 may be increased in some patients who have decreased serum free T3. PMID- 1918380 TI - Lipoprotein lipase modulates net secretory output of apolipoprotein B in vitro. A possible pathophysiologic explanation for familial combined hyperlipidemia. AB - We showed previously that net secretory output of apolipoprotein B (apo B) from cultured human hepatoma cells (HepG2) is regulated by rapid reuptake of nascent lipoproteins before they have diffused away from the vicinity of the cells. We now sought to determine if the nascent lipoproteins could be remodeled to enhance or impede reuptake. We found that lipoprotein lipase (LpL), an enzyme that hydrolyzes lipoprotein triglyceride, reduced HepG2 output of apo B to one-quarter to one-half of control. The reduction was apparent during co-incubations as short as 2 h and as long as 24 h. Heparin, which blocks receptor-mediated binding of lipoproteins, abolished the effect of LpL on apo B output, without causing enzyme inhibition. To assess uptake directly, we prepared labeled nascent lipoproteins. LpL tripled the cellular uptake of labeled nascent lipoproteins, from 15.2% +/- 0.7% to 48.7% +/- 0.3% of the total applied to the cells. Cellular uptake of 125I labeled anti-LDL receptor IgG was unaffected by LpL; thus, LpL enhanced reuptake by altering lipoproteins, not receptors. Because LpL is present in the space of Disse in the liver, we conclude that LpL may act on newly secreted lipoproteins to enhance reuptake in vivo. LpL deficiency would reduce local reuptake of apo B, which would appear as overproduction, thereby providing a mechanistic link between partial LpL deficiency and familial combined hyperlipidemia. PMID- 1918381 TI - Effects of cocaine on epicardial coronary artery reactivity in miniature swine after endothelial injury and high cholesterol feeding. In vivo and in vitro analysis. AB - The purpose of this study was to determine the effects of cocaine on vasoreactivity in the swine model. Eight miniature pigs underwent regional endothelial denudation of the left anterior descending coronary artery and were then fed a high cholesterol diet. Cross-sectional area (CSA) of coronary arteries was measured by quantitative angiography. Before denudation, intravenous cocaine (1, 3, and 10 mg/kg) decreased CSA of epicardial vessels by 19-44%. At 3 mo after the denudation, the percent reduction in CSA of the denuded vessels induced by the 10 mg/kg dose was significantly augmented compared to nondenuded vessels (59 +/- 5% vs. 48 +/- 4%, P less than 0.05). Under in vitro conditions where isometric force of isolated ring segments was measured, methoxamine (an alpha 1 agonist) or BHT-920 (an alpha 2 agonist) produced similar degrees of contraction of denuded and control vessels; however, cocaine in concentrations up to 3 x 10( 3) M did not produce contraction. These responses were unaffected by removal of the endothelium. Histologically, myointimal thickening was noted at the denuded site. The present study demonstrates an enhanced vasoreactivity of atherosclerotic coronary arteries to cocaine in vivo, the mechanism of which appears to be mediated by endogenous vasoactive substances rather than by a direct action of cocaine on vascular smooth muscle. PMID- 1918382 TI - Analysis of the gene sequences of the insulin receptor and the insulin-sensitive glucose transporter (GLUT-4) in patients with common-type non-insulin-dependent diabetes mellitus. AB - Insulin resistance is a common feature of non-insulin-dependent diabetes mellitus (NIDDM) and "diabetes susceptibility genes" may be involved in this abnormality. Two potential candidate genes are the insulin receptor (IR) and the insulin sensitive glucose transporter (GLUT-4). To elucidate whether structural defects in the IR and/or GLUT-4 could be a primary cause of insulin resistance in NIDDM, we have sequenced the entire coding region of the GLUT-4 gene from DNA of six NIDDM patients. Since binding properties of the IRs from NIDDM subjects are normal, we also analyzed the sequence of exons 16-22 (encoding the entire cytoplasmic domain of the IR) of the IR gene from the same six patients. When compared with the normal IR sequence, no difference was found in the predicted amino acid sequence of the IR cytoplasmic domain derived from the NIDDM patients. Sequence analysis of the GLUT-4 gene revealed that one patient was heterozygous for a mutation in which isoleucine (ATC) was substituted for valine (GTC) at position 383. Consequently, the GLUT-4 sequence at position 383 was determined in 24 additional NIDDM patients and 30 nondiabetic controls and all showed only the normal sequence. From these studies, we conclude that the insulin resistance seen in the great majority of subjects with the common form of NIDDM is not due to genetic variation in the coding sequence of the IR beta subunit, nor to any single mutation in the GLUT-4 gene. Possibly, a subpopulation of NIDDM patients exists displaying variation in the GLUT-4 gene. PMID- 1918383 TI - Immunosuppressive activity of 13-cis-retinoic acid and prevention of experimental autoimmune encephalomyelitis in rats. AB - Some activities of retinoids on cellular and humoral immunity have been described, but the available data are conflicting or obtained at concentrations that are toxic in vivo. In this study, we demonstrate that 13-cis-retinoic acid (13-cRA), a retinoid well tolerated in human therapy, can suppress T cell mediated immunity in rats. Treatment with pharmacological concentrations of 13 cRA prevented active as well as passive transfer experimental autoimmune encephalomyelitis (EAE) and suppressed lymphocyte responsiveness to T cell mitogens, suggesting that the drug activity included suppression of an effector T cell response. In addition, mitogen- and antigen-induced lymphocyte proliferation was inhibited in vitro in the presence of concentrations of 13-cRA equivalent to or less than those achieved in vivo, further suggesting that the prevention of EAE was due to a suppressive activity on T cell-mediated immunity. The immunosuppressive activity of 13-cRA included suppression of interleukin 2, whose production was inhibited in splenocytes. These data indicate that, in an in vivo mammalian system, 13-cRA exerts a suppressive activity on T cell-mediated immunity intensive enough to suppress an ongoing immune response, and that this effect can be achieved at nontoxic concentrations that may also be attained in human therapy. PMID- 1918384 TI - Sphingolipids are required for mammalian epidermal barrier function. Inhibition of sphingolipid synthesis delays barrier recovery after acute perturbation. AB - Stratum corneum lipids comprise an approximately equimolar mixture of sphingolipids, cholesterol, and free fatty acids, arranged as intercellular membrane bilayers that are presumed to mediate the epidermal permeability barrier. Prior studies have shown that alterations in epidermal barrier function lead to a rapid increase in cholesterol and fatty acid synthesis which parallels the early stages of the repair process. Despite an abundance of indirect evidence for their role in the barrier, the importance of sphingolipids has yet to be demonstrated directly. Whereas sphingolipid synthesis also increases during barrier repair, this response is delayed in comparison to cholesterol and fatty acid synthesis (Holleran, W.M., et al. 1991. J. Lipid Res. 32:1151-1158). To further delineate the role of sphingolipids in barrier homeostasis, we assessed the impact of inhibition of sphingolipid synthesis on epidermal barrier recovery. A single topical application of beta-chloro-L-alanine (beta-CA), an irreversible inhibitor of serine-palmitoyl transferase (SPT), applied to acetone-treated skin of hairless mice resulted in: (a) greater than 75% inhibition of SPT activity at 30 min (P less than 0.001); (b) a global decrease in sphingolipid synthesis between 1 and 3 h (P less than 0.02); (c) reduction of epidermal sphingolipid content at 18 h (P less than 0.01); (d) delayed reaccumulation of histochemical staining for sphingolipids in the stratum corneum; and (e) reduced numbers and contents of lamellar bodies in the stratum granulosum. Finally, despite its immediate, marked diminution of sphingolipid synthesis, beta-CA slowed barrier recovery only at late time points (greater than 6 h) after acetone treatment. This inhibition was overridden by coapplications of ceramides (the distal SPT product), indicating that the delay in repair was not due to non-specific toxicity. These studies demonstrate a distinctive role for epidermal sphingolipids in permeability barrier homeostasis. PMID- 1918386 TI - Red blood cells are a sink for interleukin 8, a leukocyte chemotaxin. AB - IL-8 (also known as neutrophil-activating peptide 1) is recognized as a potent effector of neutrophil functions. Several different cell types that contact blood, namely T lymphocytes, monocytes, and endothelial cells, secrete this polypeptide following stimulation by cytokines, or lipopolysaccharide. Here we show that when IL-8 is added to blood it rapidly partitions from the plasma fluid to the blood cells and that erythrocytes account for the vast majority of this binding. Analysis of 125I-IL-8 binding [( ala-IL-8]77 form) to human red cells indicates a single, 5 nM Kd affinity class of binding sites, present at approximately 2,000 per red cell representing approximately 15 nmol of red cell IL-8 binding sites per liter of blood. These sites are protease sensitive. Their binding of IL-8 is rapidly reversible and does not result in receptor internalization, although bound IL-8 is resistant to extraction by pH 3 buffer at 5 degrees C. 125I-IL-8 binding to red cells was not inhibited by epidermal growth factor or interleukin 1, but was inhibited by monocyte chemotactic peptide-1, which is not a neutrophil chemotaxin, but is a member of the same family of polypeptides as IL-8. FACS analysis of IL-8-mediated mobilization of Ca2+ in neutrophils indicates that the IL-8 bound to red cells is incapable of stimulating neutrophils. Thus, red cell absorption of IL-8 may function to limit stimulation of leukocytes by IL-8 released into blood. PMID- 1918387 TI - Interleukin-5 and the posttreatment eosinophilia in patients with onchocerciasis. AB - To understand the role of the eosinophilopoietic cytokine IL-5 in humans, the posttreatment eosinophilic response in a group of microfilaria (mf)-positive patients with onchocerciasis (n = 10) was examined before and after treatment with diethylcarbamazine (6 mg/kg for 7 d). Sequential blood samples were assessed at 24 and 1 h before treatment (baseline values), then at frequent intervals over the next 14 d. Symptom scores, skin microfilariae (mf), and peripheral blood eosinophil counts were recorded as a function of time after treatment, and serum levels of IL-5 were quantitated by a highly sensitive (sensitivity greater than or equal to 20 pg/ml) monoclonal-based ELISA. Pretreatment eosinophil counts ranged from 240 to 1,186 eosinophils/microliter (geometric mean, 675), and the mf counts from 10 to 218 per mg skin (geometric mean, 79). After an initial decline in the peripheral eosinophil count to 28 +/- 8% of pretreatment levels at 8 h after beginning treatment, the eosinophil counts steadily increased over the next 2 wk, reaching a maximum at 14 d (257 +/- 38% of pretreatment levels). Serum levels of IL-5 rose sharply from pretreatment levels to a peak of 70.5 +/- 11 pg/ml by 24 h after treatment. Serum IL-5 remained elevated over the next 2-3 d and declined toward baseline by approximately 6 d after treatment, at which time the eosinophil levels were steadily increasing. IL-3 and granulocyte macrophage colony-stimulating factor, two other cytokines implicated in eosinophilopoeisis, were not detectable in the serum at any time before or after treatment. The rise in serum IL-5 before the posttreatment eosinophilia seen in this group of patients with onchocerciasis demonstrates a temporal relationship between IL-5 and the subsequent development of eosinophilia and implicates IL-5 as an important mediator of eosinophilia in humans. PMID- 1918388 TI - The use of a brief movement restriction procedure to eliminate severe inappropriate behavior. AB - The effect of a brief movement restriction (BMR) procedure on the maladaptive behavior of two severely mentally retarded persons was evaluated using a multiple baseline research design. Following a functional analysis of the maladaptive behaviors, baseline data were collected on the frequency of smearing in a six year old boy and the frequency of aggression-destruction and stereotypic behavior in a 24 year old man. Following the baseline period a treatment package that included reinforcement for alternative behavior and BMR were first introduced for feces smearing. After feces smearing had shown a reduction with the first client the treatment package was introduced for aggression and destruction with the second client. After aggression and destruction had been reduced, the treatment package was added for stereotypy. The treatment package completely eliminated each of the target behaviors and they remained absent during a long follow-up period. PMID- 1918385 TI - Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta. AB - The regulation of type 1 plasminogen activator inhibitor (PAI-1) gene expression was studied in vivo employing a murine model system. Nuclease protection analysis revealed relatively high concentrations of PAI-1 mRNA in the aorta, adipose tissue, heart, and lungs of untreated CB6 (BalbC X C57B16) mice. Treatment of CB6 mice with LPS, TNF-alpha, or transforming growth factor-beta (TGF-beta) increased the steady-state levels of PAI-1 mRNA within 3 h in all tissues examined. However, the greatest responses to TGF-beta were observed in adipose tissue and the kidney, while LPS and TNF-alpha strongly stimulated PAI-1 gene expression in the liver, kidney, lung, and adrenals. In C3H/HeJ mice, which exhibit defective TNF-alpha release in response to LPS, the response of the PAI-1 gene to LPS was severely attenuated. However, injection of these mice with TNF-alpha increased PAI-1 mRNA in a tissue-specific pattern strikingly similar to that observed in LPS-treated CB6 mice. These results demonstrate that the PAI-1 gene is regulated in a complex and tissue-specific manner in vivo, and suggest a role for TNF-alpha in the response of the PAI-1 gene to sepsis. PMID- 1918389 TI - The role of private body consciousness and anxiety in the report of somatic symptoms during magnetic resonance imaging. AB - The present study examined an information processing model of symptom reporting (Ahles, Cassens, & Stallings, Journal of Behavior Therapy and Experimental Psychiatry 18, 215-222, 1987) in a medical sample during an anxiety-arousing diagnostic medical evaluation. The predisposition to attend to physical sensations (private body consciousness), state anxiety, and symptom reporting were assessed in 47 patients undergoing a magnetic resonance imaging (MRI) procedure. The results of this study provide further support for the information processing model; the interaction between private body consciousness and state anxiety significantly predicted symptom reporting during the MRI. The pattern of results points to attention to physical sensations and anxiety as important mediators of symptom reporting. PMID- 1918390 TI - The therapeutic use of tape-recorded repetitions of flooding stimuli. AB - This clinical report describes an enhancement of imaginal flooding therapy developed in clinical practice with outpatient phobics. During the session, anxiety-producing fantasies are solicited, and the verbalizations immediately preceding peaks in emotional arousal are captured on a three-minute repeating "endless loop" cassette tape. Patients' repeated exposure to the recording, in the office and as homework, enhances the efficiency and economy of imaginal flooding. PMID- 1918391 TI - A note on eye movements and relaxation. AB - Eye movements and certain visual mechanisms appear to be related to states of relaxation and levels of wakefulness. The hatha yoga tradition in its historical and contemporary forms uses certain eye 'exercises' or postures to induce relaxation and reduce arousal. Visual correlates of the alpha state are well known. These phenomena may be involved in the success of the new eye desensitization procedure. PMID- 1918392 TI - Treatment of an adolescent with bowel movement phobia using self-control therapy. AB - This report describes a self-control treatment of an adolescent with a highly unusual and severely debilitating phobia of having bowel movements in public. The treatment focused predominantly on helping the adolescent to modify his maladaptive thinking and also included role plays, graduated exposure, and homework assignments. Multimethod and multisource assessment data were collected as well as measures of social validity. Treatment gains were maintained at 3 and 6 months follow-up. PMID- 1918393 TI - Bedtime fading in the treatment of pediatric insomnia. AB - In this paper, the sleep-wake cycles of two children with severe sleep problems were regulated by delaying bedtimes, thus increasing the probability of short latency to sleep onset. A fading procedure was then utilized to advance the bedtimes and gradually increase duration of sleep. Several treatments had previously been attempted with both of these patients without success. The advantages of this treatment over other interventions for pediatric sleep disorders are discussed. PMID- 1918394 TI - Behavioral treatment of a case of psychogenic urinary retention. AB - The case involved a thirteen-year-old girl with a history of different urological disorders who since the age of four showed several rituals associated with micturition as well as progressively intense urinary retention. Micturition occupied 2 to 12 hours a day. Treatment consists of systematic desensitization through imagery and in vivo together with progressive response prevention of ritualized behaviours. Cognitive therapy and parent counselling is also used. Normality is attained after 7 weeks treatment and maintained at 18 months follow up. Psychiatric diagnosis is simple phobia to micturition. PMID- 1918395 TI - An adapted language training strategy in the treatment of an electively mute male child. AB - The present study investigated the usefulness of an Adapted Language Training Program in the treatment of an electively mute seven-year-old male. Training utilized a multiple baseline across behaviors single subject design. Four phases of treatment focused on non-verbal attending, verbal imitative responding, and functional language responding. Systematic attempts at promoting generalization of verbal responses across situations and persons were employed throughout the language program. A 90% appropriate response criterion was reached for all measures. Non-verbal attending and imitative verbal responding remained above criterion at the termination of treatment, but functional language responding regressed to below criterion. Generalization of verbal responses was noted outside of the training sessions. PMID- 1918396 TI - Costing of pathology services in the United Kingdom National Health Service. PMID- 1918398 TI - Blood component treatment: a retrospective audit in five major London hospitals. AB - A retrospective audit of 200 transfusion episodes involving the use of platelets or fresh frozen plasma (FFP) was performed in five hospitals in London. It examined the currently used practices of transfusion and assessed the appropriateness of blood component treatment. It was necessary to search for an excess of case notes to provide a sufficient number of patients for review. In 61.5% of cases the reason for using the components was not stated. Inadequate documentation of the use of blood components occurred in 66% of cases. An accepted clinical indication for the use of components was evident in only 36% of the total; inappropriate use of FFP was particularly apparent. It is concluded that many aspects of transfusion practice need to be improved. PMID- 1918397 TI - Pathological mimics of chronic inflammatory bowel disease. AB - When all of the macroscopic and microscopic features of Crohn's disease and ulcerative colitis are present, the correct diagnosis is usually made without difficulty. When some of the changes are absent, the accuracy of diagnosis is reduced. This review has outlined those diseases which feature some of these pathological changes and may masquerade as idiopathic chronic inflammatory bowel disease. Some of the pathological mimics are iatrogenic while other common diseases, such as bacterial infection, ischaemia, and diverticulosis may produce confusing histological appearances. The picture is complicated by the fact that many of these pathological imitators may themselves cause or predispose to chronic inflammatory bowel disease, or may complicate chronic inflammatory bowel disease. For example, drugs and infectious agents are recognisable causes of relapse in ulcerative colitis; Crohn's disease may cause diverticulitis in patients with diverticulosis; and lymphoma may complicate ulcerative colitis. It behooves all practising histopathologists to recognise these mimics of ulcerative colitis and Crohn's disease to ensure appropriate management for patients with inflammatory pathology of the intestines. PMID- 1918401 TI - Colour perception in pathologists: the Farnsworth-Munsell 100-hue test. AB - The value of many histological stains depends on the ability of the observer to differentiate colour. This ability was assessed in 30 histopathologists and cytopathologists of varying experience using the Farnsworth-Munsell 100-hue test. As a group, the pathologists performed better than a reference population. Twenty eight subjects showed a wide ranging ability to differentiate colour: none was colour blind. Three of the 30 pathologists, however, fell below the twentieth centile for normal subjects and only one was aware of this deficiency! They may unknowingly misinterpret subtle stains. Two of these three had specific and major defects which could affect their ability to interpret a wide range of less subtle stains. Those with the poorest colour discrimination were not those with the least experience of microscopy. Pathologists should be apprised of the importance of their ability to discriminate colour, and that formal colour vision testing of prospective histopathologists may be appropriate. PMID- 1918399 TI - Antibiotic treatment and associated prolonged prothrombin time. AB - The incidence and type of pathology causing a prolonged prothrombin time and clinical bleeding episodes were assessed in a multicentre study of 1109 patients receiving cefotetan, a N-methyl-thiotetrazole (NMTT), or equivalent antibiotics. There was no significant difference in the incidence of a prolonged prothrombin time (9.9% with cefotetan, 8.0% with comparable antibiotics) of clinical bleeding episodes. However, prothrombin time increases of greater than 12 seconds were significantly (p = 0.002) greater with cefotetan (3.8%) than with comparators (0.8%). In both antibiotic groups increases in prothrombin time were more likely following surgery and in patients who were older, with a high platelet count, low albumin, or higher urea and creatinine concentrations. All antibiotic treatment can be associated with prolonged prothrombin times and new agents should always be assessed in a large multicentre study before the practical, clinical importance of haemostatic defects can be defined. PMID- 1918400 TI - Diamond-Blackfan syndrome and neutropenia. AB - Neutropenia is a rare complication of Diamond-Blackfan syndrome (congenital hypoplastic anaemia). Three patients are reported: all had neutropenia as well as anaemia, and to investigate the cause of the neutropenia culture of bone marrow for granulocyte-macrophage colony forming cells (GMCFCs) was performed. Two cases had a low incidence of GMCFCs, but the third case had a high incidence. These findings suggest that myeloid precursors can be abnormal in Diamond-Blackfan syndrome and that the mechanism of neutropenia may, like that of anaemia, vary from patient to patient. PMID- 1918402 TI - Video absorbtiometry in diagnostic cytology: description of a new technique and a preliminary statistical evaluation. AB - Cytological specimens from 21 patients were examined using digital video microscopy. The staining characteristics of cells incubated with hydroquinone and the tetrazolium stain MTT were analysed using a novel procedure that is independent of morphological features and relies on characteristics of the frequency distribution of the localised (pixel) absorbances of the cellular images. The properties of the distribution of absorbances were assessed by a number of procedures. Comparisons were made of nine malignant and 12 non malignant cytological samples, obtained mainly from pleural and peritoneal fluid. The data showed significant differences between the sets of samples which may be of value in cytological diagnosis. In the material examined all the malignant samples exhibited a positive skewness with the alpha-3 test (the mean alpha-3 value being greater than 0.5); this was true in only two of 12 non-malignant samples. This analytical technique, which is largely independent of morphology, magnification, and absolute absorbance values, seems to hold promise for the simplification and automation of cytological screening procedures. PMID- 1918403 TI - Immunoglobulin heavy chain patterns in reactive lymphadenopathy. AB - Thirty one lymph nodes taken from 24 benign reactive cases, three cases of angiolymphoid hyperplasia with eosinophilia, one case of Kimura's disease and three cases of Hodgkin's disease, were stained for immunoglobulin heavy chains IgG, IgM, IgA and IgE using the peroxidase-antiperoxidase method. Reticular staining of germinal centres and cells containing immunoglobulin in germinal centres and extrafollicular regions were features of all groups. No staining pattern was diagnostic for any of these conditions and in particular, the reticular staining pattern of IgE in the germinal centres that is frequently reported in Kimura's disease and in angiolymphoid hyperplasia with eosinophilia was non-specific. PMID- 1918404 TI - Silver enhancement of polymerised diaminobenzidine: increased sensitivity for immunoperoxidase staining. AB - Unambiguous identification of lymphocytes is sometimes difficult because of weak immunostaining of the cell membrane immunoglobulins. A simple method of intensifying the diaminobenzidine (DAB) peroxidase reaction was therefore devised. Paraffin wax sections of formalin fixed tonsils and lymphomas were digested with trypsin and immunostained for kappa and lambda light immunoglobulin chains and CD3 antigen by various peroxidase linked detection systems. After reaction with hydrogen peroxide and DAB the sections were immersed in methenamine silver solution at 60 degrees C for three to seven minutes. The light brown stain on the cell membranes of the mantle zone lymphocytes became dark brown and the stronger stain of the plasma cells became black. Mantle zone B lymphocytes and CD3 positive T lymphocytes were precisely outlined even at low magnification and the lymphomas were easily classified as monoclonal or polyclonal. At high magnification, staining was clearer than with the immunogold-silver stain. Cryostat and paraffin wax sections of other tissues immunostained for various antigens showed similar intensification. Silver methenamine provides an easy means of increasing the sensitivity and visual impact of an immunoperoxidase/DAB reaction in any preparation. PMID- 1918405 TI - Use of a tissue adhesive to repair fetal bodies after dissection. AB - The repair of fetal bodies after dissection is extremely difficult because of the delicacy of the skin. A tissue adhesive, Histoacryl blue, was used to repair bodies that had been dissected either before or after immersion in formalin. The repairs were achieved rapidly and neatly. The technique was easy to learn and, providing the method of repair described was followed, there was no breakdown subsequently. The body cavities and reflected skin surfaces were lightly dried with absorbent paper towels and the body loosely packed with cotton wool. "Holding lines" of glue were made and a mid-line strip of glue was applied to the sternum, abdomen, and skull vault, allowing the skin edges to align neatly. Care must be taken to avoid using excess glue as this produces an exothermic reaction. It is recommended that if a fetus has to be repaired after dissection Histoacryl blue will give a good result. PMID- 1918406 TI - Selective location of palisaded myofibroblastoma with amianthoid fibres. AB - The occurrence of a palisaded myofibroblastoma with amianthoid fibres in the left inguinal lymph node of a 51 year old man prompted an investigation of the factors underlying its exclusive location. The antigen profile was characterised which confirmed the homogeneous expression of vimentin and smooth muscle actin as well as the lack of desmin. Use of monoclonal antibodies to check for a differential distribution of myofibroblasts and the putative cell of origin of palisaded myofibroblastoma showed that inguinal lymph nodes have abundant vimentin and actin positive cells and desmin negative cells. This suggests that the selective occurrence of myofibroblastoma is related to the nodal microenvironment, providing a source of available and potentially proliferating myofibroblasts. Mast cells abounded in this lesion, particularly around amianthoid fibres, as well as in pelvic and inguinal lymph nodes. In view of the known role of mast cells in interstitial matrix degradation it is postulated that the core of amianthoid fibres represents degraded interstitial matrix, analogous to the sclerotic areas commonly found in the above mentioned lymph node groups, while the peripheral spokes, so peculiar to this entity, are the result of vimentin and smooth muscle actin, directly shed by proliferating myofibroblasts. PMID- 1918407 TI - Simple and specific test for measuring lipid peroxides in plasma. AB - The specificity of an iodometric assay for measuring lipid peroxides in lipoproteins was tested, compared with the fluorimetric thiobarbituric acid assay, and adopted for detecting lipid peroxide in plasma samples. Oxidation of low density lipoproteins in vitro by Cu2+, lipoxidase, and phagocytosing polymorphonuclear leucocytes was sensitively detected by the iodometric assay. Unlike the thiobarbituric acid assay, neither non-lipid substances commonly present in plasma, nor platelet or polymorphonuclear leucocyte by-products interfered with the iodometric assay. The iodometric assay measured a normal mean (SD) plasma lipid peroxide concentration of 10.8 (2.1) microM; n = 63. Two weeks after the start of a high cholesterol diet in rabbits (n = 5), a sixfold increase in plasma lipid peroxide concentrations was measured by iodometric assay. The specificity of a simple and sensitive iodometric test of lipid peroxidation was superior to that of the thiobarbituric acid assay. This iodometric assay should therefore provide a much more accurate assessment of lipid peroxide in plasma samples. PMID- 1918410 TI - Evaluation of the Microring YT system for identifying clinical yeast isolates. AB - The Microring YT is a commercial system for identifying clinical yeast isolates. The system uses a series of discs impregnated with inhibitory agents mounted on a ring. The pattern of growth and inhibition produced provides a six digit code which can be compared with a table provided by the manufacturer. The performance of this system was compared with the API 32C in the identification of 606 yeast isolates (355 clinical and 251 environmental strains). The Microring YT system was in 72.6% agreement with the API 32C system. The sensitivity of identification of different species varied from 38% to 100%. The API 32C system has a more extensive database than the Microring YT and is thus more reliable for use, but it is considerably more expensive. It is concluded that although the Microring YT is cheap, easy, and convenient to use, it is inadequate for many common Candida species. PMID- 1918408 TI - Immune responses to Helicobacter pylori in children with recurrent abdominal pain. AB - The systemic immune response to Helicobacter pylori was examined in 69 children with recurrent abdominal pain and upper gastrointestinal symptoms. Twenty one (30%) children were histologically positive for H pylori. Eighteen of the 21 positive subjects and two H pylori negative subjects (one with normal mucosa, one with lymphocytic gastritis) were positive for H pylori IgG antibodies by enzyme linked immunosorbent assay (ELISA) (86% sensitivity, 98% specificity). In children with H pylori associated gastritis, there was a significant positive correlation (p less than 0.05) between IgG antibody titres and patient age. Intra assay comparison of sera from histologically negative adults with those of histologically negative children showed that the cut off for positivity in the ELISA for adults was greater than that for children. Immunoblotting showed IgG positivity in 20 of the 21 patients with H pylori infection (95% sensitivity). Both ELISA and immunoblotting for IgA and IgM H pylori antibodies had poor discriminatory value for determining infection. Serological detection of H pylori IgG antibodies seems to be valuable in the assessment of children presenting with recurrent abdominal pain and other gastrointestinal symptoms, but assays must first be validated in paediatric populations. PMID- 1918409 TI - Problems of thermonuclease detection for identifying Staphylococcus aureus in blood culture broths. AB - The detection of thermonuclease by the Oxford strain and eight clinical isolates of Staphylococcus aureus in a variety of bacteriological broths with and without added blood was examined using a toluidine blue-DNA-agar plate method. In Isosensitest, brain-heart infusion, tryptic soy, nutrient and gas-liquid chromatography broths (all of which do not contain liquoid) thermonuclease detection was uncomplicated. In Bactec broths (containing liquoid) detectable thermonuclease activity was greatly reduced in the absence of blood. The addition of 10% blood to the Bactec broths restored the activity. Liquoid was shown to be responsible for the inhibition of thermonuclease activity, and its effect could be neutralised by the addition of blood, albumin, or haemoglobin. In specimens containing no blood, or insufficient blood to neutralise the liquoid in culture broths, more has to be added to prevent false negative reporting of S aureus. This can be done after growth at the time of thermonuclease testing. Clinical consequences of delayed identification of S aureus in routine blood cultures may be serious. The application of the thermonuclease test to blood culture broths is both fast and specific. PMID- 1918411 TI - A tumour, a cell, a misunderstanding: trabecular (Merkel cell) carcinoma of the skin. AB - Trabecular carcinoma has been renamed as Merkel cell carcinoma because, ultrastructurally, tumour cells resemble Merkel cells of the skin. Recently, evidence of exocrine (sweat gland) differentiation in some trabecular carcinomas has been reported. These findings raise two possibilities: (1) trabecular carcinomas are a heterogeneous group of lesions; or (2) that trabecular carcinomas are glandular tumours, in which exocrine features are rarely detected. PMID- 1918412 TI - Should eye protection be worn when performing necropsies? AB - One hundred necropsies were performed by four junior pathologists wearing safety spectacles. The number of blood splashes on the spectacle surfaces were counted after each necropsy. Splashes were found after 22 necropsies (range 10-34%), with higher numbers being seen among the more junior grades of pathologist. This suggests that the use of safety spectacles should be considered by all pathologists performing necropsies. PMID- 1918413 TI - Cerebrospinal fluid concentration of fibronectin in meningitis. AB - Fibronectin concentrations in the cerebrospinal fluid were assessed in 20 patients with acute meningitis using a turbidimetric immunoassay. A significant increase in fibronectin concentrations was observed in patients with bacterial meningitis; decreased concentrations were observed in patients with viral meningitis. The determination of fibronectin concentration in patients with bacterial meningitis may represent a useful marker in differentiating bacterial from viral meningitis. PMID- 1918414 TI - Assessment of the Glycotronic C blood glucose meter. AB - The performance of the Glycotronic C blood glucose meter, a pocket sized glucose strip meter, was assessed on the ward and in the laboratory. Theoretically there is a relation between blood glucose concentration, plasma glucose concentration and haematocrit when glucose is measured using conventional methods. The Glycotronic C meter would yield results about 20% greater than those of a conventional instrument when used to measure plasma glucose and about 15% less than a conventional instrument when used to measure the blood glucose concentration of a neonate. The Glycotronic C is easy to use and gives an acceptable performance for near patient use; it compares well with its current British competitors. PMID- 1918415 TI - Sudden postoperative death caused by unheralded Mallory Weiss tears. AB - Mallory Weiss tears are a common cause of upper gastrointestinal bleeding, typically reported as following repeated vomiting after an alcoholic binge. This association may have been overemphasised, and these lesions could be caused by a wide range of spontaneous and iatrogenic events. A case of sudden postoperative death caused by massive haematemesis, unheralded by any evidence of vomiting or retching, as a result of Mallory Weiss tears is reported. PMID- 1918416 TI - Platelet satellitism and alpha granule proteins. AB - Blood smears from a patient with severe generalised arteriopathy and an occluded synthetic femoropopliteal graft showed the phenomenon of EDTA dependent adherence of platelets to neutrophils (platelet satellitism). Immunoenzymatic staining with a monoclonal antibody to thrombospondin showed that adherence to neutrophils exclusively involved platelets that stained strongly positive for thrombospondin, while negative or weakly positive platelets showed no tendency to adhere. There was no increase in platelet surface immunoglobulins. This suggests a possible role for thrombospondin or some other cytoadhesive platelet alpha granule protein in mediating the adherence of platelets to neutrophils in cases of satellitism. PMID- 1918417 TI - Turnround times in a microbiology laboratory. PMID- 1918418 TI - Serum alanine transaminase (ALT) reference range in Italy. PMID- 1918419 TI - Cost effectiveness of dipsticks. PMID- 1918420 TI - Treatment of bulimia nervosa with antidepressant medication. PMID- 1918421 TI - Placebo-controlled trial of venlafaxine for the treatment of major depression. AB - Results are presented of the first double-blind, placebo-controlled trial of a novel antidepressant venlafaxine, which preclinically has demonstrated serotonin, norepinephrine, and dopamine reuptake inhibiting effects. Sixty outpatients meeting DSM-III-R criteria for major depression were randomized to receive 6 weeks of treatment with one of three fixed doses of venlafaxine--25 mg three times a day, 75 mg three times a day, or 125 mg three times a day--or placebo. Significant improvement was observed in depression scores at all doses, with the high dose resulting in earlier improvement, by week 2. For the combined venlafaxine treatment groups, 68% achieved a moderate or marked improvement on the Clinical Global Impression scale, compared with only 31% for the placebo group. Venlafaxine was well tolerated, and nervousness, sweating, and nausea were the only adverse effects observed more frequently with drug compared with placebo. PMID- 1918422 TI - A controlled comparison of adjuvant lithium carbonate or thyroid hormone in clomipramine-treated patients with obsessive-compulsive disorder. AB - In this study, 16 patients with obsessive-compulsive disorder (OCD) who had partially improved during at least 6 months of treatment with clomipramine were sequentially treated with triiodothyronine and lithium carbonate in an 8-week double-blind cross-over study. Both triiodothyronine and lithium carbonate have been reported to be efficacious in open trials as adjunctive agents when combined with tricyclics in the treatment of OCD and depressed patients. However, in our controlled study, OCD and depressive symptoms, as assessed by standardized rating scales in the patient group as a whole, did not significantly change after either adjuvant treatment. Further analysis on an individual patient basis revealed that neither adjuvant medication was associated with a clinically meaningful change (greater than 25%) in OCD symptoms. However, lithium, but not triiodothyronine, adjuvant therapy was associated with a 25% or greater reduction in depression scores in 44% of the patients. This controlled study lends further support to the contention that OCD may represent a disorder with characteristics distinct from affective disorders. PMID- 1918423 TI - Estazolam treatment of insomnia in generalized anxiety disorder: a placebo controlled study. AB - Estazolam, a triazolobenzodiazepine with an intermediate elimination half-life, has been shown previously to be an effective and safe hypnotic in insomniacs without concomitant psychiatric illness. Our study of the efficacy of estazolam in patients with insomnia associated with generalized anxiety disorder began when 108 patients meeting criteria for generalized anxiety disorder (mean total score of Hamilton Rating Scale for Anxiety [HAM-A] = 22.0 +/- 3.1 [SD]) and insomnia were given single-blind placebo for 7 nights. Nine patients whose anxiety and/or insomnia improved were dropped as placebo responders. The remaining 99 patients were randomly allocated (1:1) to double-blind treatment with either estazolam 2.0 mg or matching placebo for 7 nights. Hypnotic efficacy, as determined by patient completed sleep questionnaires, was statistically significant for estazolam 2.0 mg versus placebo for all sleep indices (p less than 0.01). Patients treated with estazolam 2.0 mg showed significantly greater improvement in anxiety than those receiving placebo on the mean total score of HAM-A ([placebo, -3.4; estazolam, 7.1; p less than 0.001] and without the insomnia item [placebo, -2.7; estazolam, 5.5; p less than 0.001]). Anxiety scores on the State-Trait Anxiety Inventory showed greater improvement in the estazolam group, but without statistical significance (p = 0.237). Estazolam 2.0 mg is an effective hypnotic in patients with generalized anxiety disorder and appears to have a favorable anxiolytic action. PMID- 1918425 TI - Disinhibition and anger outbursts in adolescents treated with clonazepam. PMID- 1918424 TI - Adjunctive lithium carbonate in nortriptyline-resistant elderly depressed patients. AB - Recent reports supporting the use of lithium carbonate as an adjunct to tricyclic antidepressants for the treatment of refractory depression have not utilized standardized tricyclic antidepressant therapy, nor have they addressed the efficacy of lithium augmentation in a geriatric population. A 3-week open trial was added to the medication regimen of 15 elderly depressed inpatients who had already failed 4 weeks of therapeutic levels of nortriptyline. Treatment response was determined by the 17-item Hamilton Rating Scale for Depression (HAM-D). Two of 15 partial responders before lithium augmentation became complete responders. Of the remaining 13 "nonresponders" before lithium augmentation, one had a complete response, 7 had a partial response and 5 remained nonresponders. Although there was a mean HAM-D change of 8.3 points after lithium augmentation (24.7 +/- 5.9 to 16.4 +/- 6.8, p less than .001), when considering the previously reported similar efficiency of extended nonaugmented nortriptyline, these data do not strongly support lithium augmentation in elderly subjects who fail to respond after 4 weeks of nortriptyline. Further study is needed to determine what role, if any, lithium augmentation should play in the treatment of geriatric depression. PMID- 1918426 TI - On the alert for clonazepam (Klonopin) versus clonidine. PMID- 1918427 TI - Does imipramine worsen atypical depression? PMID- 1918428 TI - Increased sensitivity to lithium-induced neurotoxicity after stroke: a case report. PMID- 1918429 TI - Lithium-induced hyperbilirubinemia in an adolescent. PMID- 1918430 TI - Trazodone reduced aggressive and self-injurious movements in a mentally handicapped male patient with autism. PMID- 1918431 TI - Treatment of social phobia with bupropion. PMID- 1918433 TI - Sodium-calcium exchange and lithium action. PMID- 1918432 TI - Disseminated intravascular coagulation and acute myoglobinuric renal failure: a consequence of the serotonergic syndrome. PMID- 1918434 TI - Buspirone for the behavior problems of patients with organic brain disorders. PMID- 1918435 TI - Adolescent pregnancy: maternal weight effects on fetal heaviness: possible route to improved outcomes. AB - In a previous report of a zinc supplementation trial in pregnant adolescents zinc effect varied according to maternal weight (wt) status--normal (90-110% of expected wt), light or heavy, prompting this analysis of effects of wt status and gestational wt gain on fetal heaviness relative to length and gestational age (GA) and other pregnancy outcomes. One-third of adolescents shifted in or out of normal wt by delivery, creating seven outcome groups--light-light, light to normal, normal to light, normal-normal, normal to heavy, heavy to normal, and heavy-heavy. These wt class change groups varied significantly as to intrauterine growth (SGA, low AGA, high AGA, and LGA); by weekly grams gain per cm height (ht), birth wt, infant wt/length ratio, and occurrence of low birth wt (LBW). Infants with above average intrauterine growth had an advantage in: absolute size, length of hospital stay, rates of LBW, fetal demise, rates of low Apgar score, and "other" complications. This association between intrauterine growth and maternal wt class change suggests that promotion of wt gain might lower rates of LBW. Birthwt varied by quartiles of weekly wt change (gm) per cm ht in women grouped by their percent of expected wt: in the lowest quartile (Q1) only one group in seven reached average Bwt (3025 grams); with Q4 gain all groups did. Thus, the parameter wt gain/wk/cm ht deserves study as a tool for monitoring wt status and gain to identify those pregnant adolescents in greatest need for nutritional counseling and to set wt gain goals. PMID- 1918436 TI - The health beliefs of health fair participants. AB - The motivations and health beliefs of adults who participate in community-based health promotion were studied through a survey of 303 adults attending five community health fairs. Subjects were predominately female (69.9%), over age 60 (66.8%), and had at least yearly contact with a family physician (85.3%). Obtaining laboratory testing services was the sole reason for attendance for 47% of participants, was thought to be of much greater importance than health educational materials also offered at the health fair, and identified as providing a sense of control over personal health care. Receiving their own normal test results was perceived as assuring a "healthy" future for 86% of participants and few used these results to support erroneous health beliefs. A theme of "positive health feedback", identified through factor analysis of survey responses, may prove useful for family physicians to incorporate into more directed and useful health promotion efforts for enhanced patient participation and satisfaction. PMID- 1918437 TI - The relationship between work-related and non-work-related injuries. AB - A case-control study of occupational injuries sustained by 914 male hourly workers employed in two Tenneco manufacturing divisions in 1987 was undertaken to examine the association between occupational and non-occupational injuries. Its aim was to evaluate whether employees who experienced a work-related injury were more likely to have sustained a previous non-work-related injury compared to individuals who did not experience a work-related injury. A statistically significant association between occupational injuries and past non-occupational injuries was seen when all workers compensation (WC) claims were analyzed (OR = 1.41) and when claims involving indemnity for lost time were analyzed (OR = 1.82). In addition, both workers who had occupational low-back injuries and workers who had occupational non-low-back injuries also had significantly higher risks of such injuries from a non-occupational origin (OR = 1.91 for low-back injuries and OR = 1.44 for non-low-back injuries). The findings suggest that elements other than workplace hazards (such as life-style and physical and psychological factors) may predispose an individual to both occupational and non occupational injuries. PMID- 1918438 TI - Maternal satisfaction with primary care for children with selected chronic conditions. AB - One hundred forty mothers of children with chronic illnesses seen in two pediatric specialty clinics of a major urban teaching hospital were surveyed regarding their primary care arrangements and satisfaction with care received. Three dimensions of maternal satisfaction were measured: general satisfaction, satisfaction with access to care and satisfaction with doctor conduct (physician humaneness and technical quality). Results of multivariate analyses indicate that receipt of anticipatory guidance, access to care during evening hours and having a child in excellent reported health status were significantly associated with at least two of the three dimensions of maternal satisfaction. Findings have implications for organizing comprehensive, accessible primary care in the community, which is consistent with recent trends in child health policy. Results supported the need for enrichment of primary care for children with chronic illnesses to allow for physician continuity, provision of information and advice to families and extended office hours. PMID- 1918440 TI - Dual mode of corticothalamic synaptic termination in the mediodorsal nucleus of the rhesus monkey. AB - Electron microscopic autoradiography (EM-ARG) was used to assess the synaptic organization of corticothalamic terminals in the parvicellular division of the mediodorsal thalamic nucleus. Examination of the synaptic organization in unreacted tissue revealed several distinct synaptic types distributed among glomerular and nonglomerular regions of the neuropil. Within glomeruli, three presynaptic terminal classes were found. The majority of profiles (as many as eight to ten per glomerulus) were presynaptic dendrites (PSDs) forming symmetric synaptic contacts with a central dendrite, and occasionally with other PSDs. One or two large terminals densely packed with round vesicles (LR terminals) were also present in each glomerulus. This terminal class made multiple asymmetric contacts with the central dendrite, as well as with many PSDs within the glomerulus. Finally, small terminals with round vesicles (SR terminals) formed asymmetric synaptic junctions with PSDs in some glomeruli. PSDs and SR terminals were also found in the extraglomerular neuropil, although in different proportions than in the glomeruli. In the extraglomerular neuropil SR terminals were the most abundant terminal class and these terminals made synaptic contacts with dendrites of all sizes. PSDs were seen in considerably smaller numbers than in the glomeruli. Finally, the extraglomerular neuropil contained a moderate number of small to medium terminals that formed symmetric synaptic junctions (SF terminals) with cell bodies and dendrites of all sizes. Synaptic profiles related to corticothalamic inputs were identified by injecting the prefrontal cortex of two rhesus monkeys with 3H-leucine and -proline and analyzing the distribution and morphology of radiolabeled terminals. Quantitative analysis of the density of silver grains over different tissue compartments revealed a positive labeling index for two terminal classes: SR and LR terminals. Labeled SR terminals were concentrated in the extraglomerular neuropil and labeled LR terminals were found within glomeruli where they formed synaptic contact with the central dendrite, as well as with presynaptic dendrites of the glomerulus. In contrast to many other thalamic nuclei, cortical input to the mediodorsal nucleus arrives via two distinctive synaptic pathways, one terminating extraglomerularly and the other terminating within the synaptic glomeruli. The dual mode of corticothalamic terminations in the mediodorsal nucleus suggests a more potent and possibly different role for cortical input in the regulation of neuronal activity in this association nucleus than in sensory nuclei of the thalamus. PMID- 1918439 TI - Contributions of public health to patient compliance. AB - This paper discusses the contributions of public health to compliance in five areas: clinical trials, smoking cessation, dietary compliance, breast cancer screening and hypertension control. Public health programs have been based on a number of theoretical foundations, most notably, social learning theory and the health belief model. Social marketing, community organization, and, more recently, consumer information processing models also are important. The strongest public health programs embody an ecological approach, with interventions directed not only at individuals, but also at groups, communities and changing institutional norms. Among the most important contributions of public health interventions are: multiple levels of intervention and evaluation, tailoring to target audiences, use of social support and community organization for behavior change. Together, community health and clinical compliance-enhancing strategies can exert a synergistic impact on health behavior change. PMID- 1918441 TI - Common projection areas of antennal and visual pathways in the honeybee brain, Apis mellifera. AB - The convergence of primary sensory neurons of the antennae, higher order visual interneurons, and antennal motoneurons was analysed with neuroanatomical techniques in the honeybee, Apis mellifera. The different modalities evoke specific antennal responses in this insect. Three different fluorescent dyes were applied successively in the same preparation in order to visualise the various fiber projections from the antennae and the lobula in the brain of the honeybee. Three neuropile areas where sensory fibers of the antennae overlap with visual projection neurons from the lobula were found. Within the posterior-median protocerebrum the antennal tract T6-1 comes in close vicinity to the lobula tract LoT-9 and to some other lobula fibers that cannot be assigned to a special tract. Antennal T6-3 fibers overlap with lobula LoT-7 neurons within the posterior protocerebrum more laterally. Antennal T5 fibers arborise in the dorsal lobe and show common projection sites with lobula LoT-3 neurons. The multimodal convergence in the three common neuropiles demonstrates that these areas are important centers for multimodal information processing between sensory, motor, and descending neurons in insects. PMID- 1918442 TI - Segment-specific modifications of a neuropeptide phenotype in embryonic neurons of the moth, Manduca sexta. AB - We have studied differences in the development of segmentally homologous neurons to identify factors that may regulate a neuropeptide phenotype. Bilaterally paired homologs of the peripheral neuron L1 were identified in the thoracic and abdominal segments in embryos of the moth Manduca: each bipolar neuron arises at a stereotyped location and, at 40% of embryogenesis, projects its major process within the transverse nerve of its own segment. Shortly after the initiation of axonogenesis (approximately 41%), L1 homologs in all but the prothoracic segment (T1) were labelled specifically by an antiserum to the molluscan neuropeptide Phe Met-Arg-Phe-NH2 (authentic FMRFamide). Levels of peptide-immunoreactivity (IR) were comparable in all such segmental homologs up to the approximately 60% stage of embryogenesis, whereupon two distinct levels of peptide IR were displayed: homologs in the three most rostral segments (T2, T3, and A1; [abdominal segment 1]) showed high levels and were called Type I L1 neurons; homologs in the more caudal segments (A2-A8) typically showed low levels of IR and were called Type II L1 neurons. This segment-specific difference represented mature differentiated states and was retained in postembryonic stages. Intracellular dye fills of embryonic L1 neurons revealed that the morphogenesis of the Type I and II L1 neuron homologs was similar until approximately 48% of embryogenesis; thereafter it differed in two salient ways: (1) the cell bodies of Type II L1 neurons migrated approximately 150 microns laterally from their point of origin, and (2) the distal processes of the Type II L1 neurons contacted the heart, whereas those of Type I L1 neurons did not. Ultrastructural studies of both mature and developing L1 homologs showed that the FMRFamide-like antigen(s) localized specifically to secretory granules. Further, whereas the secretory granules in segmental homologs appeared similar initially (i.e., at approximately 50% of development), following the establishment of segment-specific differences, secretory granules found in mature Type I and II L1 neurons were cell type specific. PMID- 1918443 TI - Cell counts and maps in the larval central nervous system of the ascidian Ciona intestinalis (L.). AB - Although the ascidian tadpole larva harbors a prospectively valuable prototype of the chordate nervous system, with extensively characterized neural plate cell lineages, the simple cellular composition of the resultant central nervous system (CNS) is not documented in detail. The average total number of cells in the larval CNS of Ciona intestinalis is 335 (range +/- 4, n = 3), 65 or 66 of which reside in the nerve cord of the tail. The estimates were made by tracing and counting the number of nuclei in serial semithin (1 micron) sections cut longitudinally through three larvae, fixed no later than 2 hours after hatching. Within a single fourth larva, L4, 266 cells constituted the CNS in the trunk region of the larva, 45 of which occurred within the visceral ganglion, 215 in the sensory vesicle, and 6 in the neck between the two. Each cell was assigned to one of thirteen categories. Most (182, roughly 68%) are classified as ependymal, a specialized non-neural cell peculiar to embryonic and larval chordates, from their position lining the cavities of the neural tube's elaborations or from clear similarities in the cytological appearance to those that do. Five cells are accessory cells of the sensory structures: three lens cells and a pigment-cup cell in the ocellus, and a single pigment cell in the otolith. Of the remaining 79 cells, 36 are sensory, 17 receptors in the ocellus and 19 presumed hydrostatic pressure receptors; these lie on the right and left sides of the sensory vesicle, respectively. Eighteen of the visceral ganglion cells have been tentatively classified as neurons, as have the remaining 25 cells which form two clusters in the posterior region of the sensory vesicle. PMID- 1918445 TI - The relationship between reproductive state and "sexually" dimorphic brain areas in sexually reproducing and parthenogenetic whiptail lizards. AB - The anterior hypothalamus-preoptic area and ventromedial hypothalamus are sexually dimorphic in the reproductively active whiptail lizard Cnemidophorus inornatus. The anterior hypothalamus-preoptic area, which is involved in the control of male-typical copulatory behaviors, is larger in males, whereas the ventromedial hypothalamus, which is involved in the control of female-typical receptivity, is larger in females. In the parthenogenetic whiptail lizard C. uniparens, which is a direct descendant of C. inornatus and exhibits both male like and female-like pseudosexual behaviors, both brain areas are comparable in size to those of female C. inornatus. This study was conducted to determine whether these brain areas change in size in either species or sex during a time of year when these animals are reproductively inactive, or after removal of the gonads. In male C. inornatus both brain areas changed during reproductive inactivity (either seasonally or surgically induced) and became equivalent to the size characteristic of reproductively active female C. inornatus. When corrected for brain size, the anterior hypothalamus-preoptic area was significantly smaller in intact hibernating and castrated males than in intact males from the summer breeding season. Conversely, the ventromedial hypothalamus was significantly larger in intact hibernating and castrated males than in intact males from the summer breeding season. The two brain areas were not significantly different among the groups of female C. inornatus or parthenogenetic C. uniparens. These results suggest that 1) the brain of whiptail lizards may differentiate seasonally and 2) the female state may be a neutral one to which the male brain reverts during reproductive inactivity. PMID- 1918444 TI - The bed nucleus-amygdala continuum in human and monkey. AB - The cytoarchitecture and distributions of seven neuropeptides were examined in the the bed nucleus of the stria terminalis (BST), substantia innominata (SI), and central and medial nuclei of the amygdala of human and monkey to determine whether neurons of these regions form an anatomical continuum in primate brain. The BST and centromedial amygdala have common cyto- and chemo-architectonic characteristics, and these regions are components of a distinct neuronal complex. This neuronal continuum extends dorsally, with the stria terminalis, from the BST and merges with the amygdala; it extends ventrally from the BST through the SI to the centromedial amygdala. The cytoarchitectonics of the BST-amygdala complex are heterogeneous and compartmental. The BST is parcellated broadly into anterior, lateral, medial, ventral, supracapsular, and sublenticular divisions. The central and medial nuclei of the amygdala are also parcellated into several subdivisions. Neurons of central and medial nuclei of the amygdala are similar to neurons in the lateral and medial divisions of the BST, respectively. Neurons in the SI form cellular bridges between the BST and amygdala. The BST, SI, and amygdala share several neuropeptide transmitters, and patterns of peptide immunoreactivity parallel cytological findings. Specific chemoarchitectonic zones were delineated by perikaryal, peridendritic/perisomatic, axonal, and terminal immunoreactivities. The results of this investigation demonstrate that there is a neuronal continuity between the BST and amygdala and that the BST-amygdala complex is prominent and discretely compartmental in forebrains of human and monkey. PMID- 1918446 TI - Immunohistochemical localization of serotoninergic, enkephalinergic, and catecholaminergic cells in the brainstem and diencephalon of a cartilaginous fish, Hydrolagus colliei. AB - We localized serotonin (5-HT), leu-enkephalin (LENK), and tyrosine hydroxylase (TH) immunoreactive cells in the brain of a holocephalian, Hydrolagus colliei, by use of antibodies made in rabbit and the peroxidase-antiperoxidase technique. Only three locations contained TH+ cells, the caudal myelencephalon, the locus coeruleus, and the diencephalon. Of these locations, the diencephalon contained the most cells and the locus coeruleus the least cells. The caudal TH+ myelencephalic cells formed a single large group that spanned both the dorsal and ventral portions of the brain (A1A2). The diencephalic TH+ cells were located in the posterior tuberculum, in the ventromedial and ventrolateral thalamic nuclei, and in the inferior lobe of the hypothalamus. Hydrolagus differed from mammals and the elasmobranchs, their sister group, in that no substantia nigra (A9), ventral tegmental area (A10), or A5 cell group was found. Distribution of LENK+ and 5-HT+ cells were similar to each other; the raphe nuclei contained most of the 5-HT+ and LENK+ cells. These 5-HT+ and LENK+ cells were found at all rostrocaudal levels of the myelencephalon. The nucleus reticularis magnocellularis, reticularis paragigantocellularis lateralis, the ventral met- and mesencephalon (B7 and B9 cell groups), the hypothalamus, and the pretectal area contained additional 5-HT+ and LENK+ cells. The solitary complex contained LENK+ cells but not but 5-HT+ cells. A dorsal raphe nucleus, which is the largest 5-HT+ cell group in mammals, was absent in Hydrolagus. A dorsal raphe nucleus is present in one galeomorph shark radiation but is absent in three radiations of batoids (rays, skates, and guitarfish). Thus even within cartilaginous fish, there are differences in the distribution of neurochemicals and possibly nuclei within their brains. PMID- 1918448 TI - Intrahepatic biliary cysts in deer. AB - The gross and histological appearances of intrahepatic cysts in red and roe deer are described. It is suggested that the structures arise as anomalous developments of the biliary tree. Although not of clinical significance, these cysts may pose a problem at meat inspection. PMID- 1918449 TI - Calcium oxalate in mammalian thyroids: a re-evaluation. AB - Although calcium oxalate crystals in the thyroid have been thought to occur only in human glands, this compound may be found in thyroid glands of a wide variety of mammalian species. Mechanisms underlying the formation of these deposits and their biological significance remain unclear but various possibilities are discussed. PMID- 1918447 TI - Pathogenesis of lymphoid lesions in murine experimental listeriosis. AB - Adult female Swiss albino mice were infected intraperitoneally or subcutaneously with Listeria monocytogenes Serovar 4b or 1/2a and killed at intervals. Thymus, spleen, Peyer's patches and a variety of lymph nodes, including the jejunal (mesenteric), mediastinal, lumbar, mandibular and superficial inguinal, were examined by histopathology and by immunocytochemistry for detection of L. monocytogenes antigen. Similar results were obtained with both Serovars and by both routes of inoculation used. In the spleen, L. monocytogenes was detected, by immunoperoxidase staining, as soon as 4 h after inoculation, inside phagocytic cells located predominantly in the marginal zone of the white pulp. This was followed by inflammation, necrosis and depletion of lymphoid cells, which extended in extreme cases to the whole organ. Inflammatory lesions diminished progressively at 5 to 6 days after inoculation. In animals dying of the infection, a severe necrotizing splenitis was present. Depletion of lymphoid cells and inflammatory changes were widespread in the lymph nodes and to a lesser extent in the Peyer's patches. An extensive necrotizing lymphadenitis was the prominent lesion in severely affected nodes. Inflammatory lesions and detection of L. monocytogenes antigen started around the venules of high endothelium. A thymus depletion, not associated with the multiplication of bacteria in the organ, was also a constant feature of the infection. This study suggests that L. monocytogenes (1) is transported to the spleen and to the lymph nodes by phagocytes, entering the organs by the marginal sinus in the spleen and by the venules of high endothelium in the lymph nodes; (2) multiplies in these cells as well as in neutrophilic granulocytes (the latter rapidly migrate to the affected zones); and (3) induce a splenitis and lymphadenitis, involving predominantly T cell-dependent areas, with a necrotizing component in severe cases. From our observations it is concluded that infection of the lymphoid system is a major feature in the pathogenesis of murine listeriosis. PMID- 1918450 TI - Pancreatic adenocarcinoma with osseous metaplasia in a ferret. AB - A poorly differentiated pancreatic adenocarcinoma with regional lymphatic, hepatic, enteric and pulmonary metastases was diagnosed in an adult European ferret (Mustela putoris furo). The ferret showed clinical signs including a progressive, marked abdominal enlargement owing to ascites. Microscopic findings included intralesional osseous metaplasia. Exocrine pancreatic neoplasms in ferrets are rarely reported compared with neoplasms with endocrine differentiation. PMID- 1918451 TI - The use of fluorescein-conjugated monoclonal antibodies, cell culture and transmission electron microscopy to detect Chlamydia psittaci and associated lesions in experimentally infected mice. AB - An immunofluorescence test based on a monoclonal antibody (mAb) was used to demonstrate chlamydiae in formalin-fixed and paraffin wax-embedded tissues from 10 adult mice experimentally infected by the oral route with Chlamydia psittaci isolated from the fetal membranes of an aborted ovine fetus. Samples of lung, jejunum and spleen were examined by bright-field microscopy, immunofluorescence and transmission electron microscopy, and were cultured for chlamydia in McCoy cells. These tissues were compared with those of two control mice. All infected mice had splenic hyperplasia and two had pneumonia. The lung appeared to be the target organ for C. psittaci administered by the oral route. Chlamydiae were identified in the lungs of five mice by immunofluorescence, bright-field and transmission electron microscopy. Chlamydiae were cultured from the jejunum of two mice and the spleen of one, but could not be identified at these sites by other methods. Immunofluorescence with an anti-chlamydia mAb was useful for detecting chlamydial antigen in formalin-fixed paraffin wax-embedded samples. PMID- 1918452 TI - The effect of malnutrition on vaccination against Dermatophilus congolensis infection in ruminants. AB - Vaccination against Dermatophilus congolensis was carried out in groups of lambs raised on optimal or energy deficient diets. The groups differed significantly in weight, body condition score and plasma total protein and albumin. All animals were then challenged with D. congolensis in a dose response infection model. The vaccine was effective in the well nourished animals, reducing the number of affected lambs in the vaccinated group and the severity of the lesions and increasing the minimum dose required to cause infection. In contrast, all of the vaccinated energy-deficient lambs developed lesions. There was some evidence of vaccine effect in these animals but this was not as marked as that seen in the well nourished lambs. The malnourished lambs, vaccinated and non-vaccinated, took longer to heal than the well nourished groups. Resistance to challenge was not associated with serum antibodies or skin test reactivity to D. congolensis antigens. PMID- 1918453 TI - Experimental copper and heliotrope intoxication in sheep: morphological changes. AB - Young Merino wethers were used to determine the effects of copper and heliotrope, fed together or separately, on the development of toxicity and the concentration of trace elements in the liver and kidney. In one experiment copper and heliotrope were given concurrently, in a second experiment heliotrope was fed for 12 weeks and copper administration commenced 8 weeks later. The 10 sheep fed heliotrope alone did not show signs of clinical illness but one died and was found to have severe liver damage. Eleven sheep were given copper alone and three developed the clinical signs and lesions of haemolysis. Fourteen sheep were given copper and heliotrope and 13 became ill. Of these, three developed haemolysis, eight became jaundiced and two became weak without developing jaundice. The concentrations of copper in the livers of control and heliotrope-treated sheep, were comparable. In the animals given copper alone, the concentration of copper in the liver was twice as high as that in controls and in those given heliotrope and copper, it was three times as high as in the liver of control sheep. Feeding heliotrope alone induced the histological changes of pyrrolizidine alkaloid toxicity in the liver, but this was not associated with an excessive accumulation of copper or the development of clinical illness. However, it did predispose the animals to the effects of a second toxin since giving heliotrope and copper concurrently, or giving copper subsequent to feeding heliotrope, markedly enhanced the toxicity of the two substances and caused an excessive accumulation of copper in the liver. PMID- 1918454 TI - Flow cytometric analysis of cellular DNA content in paraffin wax-embedded specimens of canine mammary tumours. AB - Flow cytometric analysis of DNA content was performed on 72 formalin-fixed, paraffin wax-embedded samples of canine mammary tumours. DNA content was correlated with histological appearance, stage of the tumour, and survival after mastectomy. All benign tumours (14 cases) were diploid. Amongst the malignant tumours, a higher incidence of aneuploid tumours (50 per cent) was observed in cases with lymph nodal metastases in comparison with those without metastases (26 per cent). All dogs with benign tumours survived for at least two years after mastectomy and so did 26 (81 per cent) of 32 DNA diploid malignant cases without metastases. A 67 per cent (eight of 12 cases) survival rate was found in the dogs with DNA aneuploid malignant tumours without metastases, while a very low survival rate (17 per cent) was observed in the group with malignant tumours with metastases, independently of the extent of ploidy. PMID- 1918456 TI - Skin and bones. I. AB - Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. Part I of our review discusses the first two categories. PMID- 1918455 TI - Intestinal changes in puppies infected with Toxocara canis. AB - Small intestinal histopathology and absorption were examined in Beagle puppies infected with either a moderate or a low burden of Toxocara canis. Infection with T. canis significantly reduced absorption of xylose, but only slightly delayed absorption of para-aminobenzoic acid. Fat assimilation was reduced and faecal proteolytic activity was increased. A significant reduction in villous height occurred and was inversely related to the extent of the infection. Villous goblet cell numbers, particularly those in the luminal third of the villus, were lowest and crypt goblet cell numbers were highest in the most heavily infected of the puppies. Villous goblet cell numbers increased rapidly after treatment of the puppies with piperazine or after the spontaneous elimination of the T. canis infection while crypt goblet cell numbers were less affected by elimination of the parasites. Intra-epithelial lymphocyte numbers were lowest in 33- to 37-day old puppies infected with greater than 127 T. canis and highest in 44- to 46-day old puppies losing their infection. Infection with T. canis had no apparent effect on mast cell numbers or pyroninophilic cell numbers in the lamina propria. PMID- 1918457 TI - Immunopathologic study of skin lesions in dermatomyositis. AB - To determine the phenotype of skin infiltrates in affected and uninvolved skin from patients with dermatomyositis, immunohistochemical studies with 10 murine monoclonal antibodies were carried out on 25 skin biopsy specimens. Dermal infiltrates consisted predominantly of HLA-DR-expressing macrophages and T lymphocytes, especially of the CD4 subset. B lymphocytes, as defined by positive staining for Leu-12, were absent. Epidermal Langerhans cells were absent or decreased in some areas of affected skin but the total number was normal. OKT6+ cells were present in some dermal mononuclear infiltrates in close contact with lymphocytes. We observed reduced HLA-DR positivity of dermal capillary endothelia. These findings are apparently different from dermatomyositis muscle infiltrates but are similar to those in skin affected by cutaneous lupus erythematosus. Our observations support the concept that, in autoimmune diseases, cellular infiltrates may be more organ-specific than disease-specific. PMID- 1918458 TI - Skin replica analysis of photodamaged skin after therapy with tretinoin emollient cream. AB - Computerized image analysis of silicone replicas, a reproducible, objective technique for measuring skin topography, was used in addition to clinical measures in two multicenter, double-blind, randomized, controlled studies of tretinoin emollient cream, a new formulation for treating photodamaged skin. Previously, the skin replica technique had been successfully used in a pilot study of tretinoin 0.05% cream by one investigator. In the present studies, subjects treated for 24 weeks with tretinoin emollient 0.05% cream consistently showed more improvement in skin topography than did vehicle-treated patients. A 0.01% concentration of tretinoin emollient cream also improved skin topography to a greater extent than the vehicle, while the lowest concentration tested (0.001%) showed little difference from vehicle. These results, reflecting a smoothening of the skin surface in tretinoin emollient cream-treated subjects, were consistent with clinical data showing greater improvement in fine wrinkling and roughness after tretinoin emollient cream therapy than after vehicle therapy. Findings from these multicenter studies confirm the value of the skin replica technique and help establish the efficacy of tretinoin emollient 0.05% cream for photodamaged skin. PMID- 1918459 TI - Grafting of leg ulcers with undifferentiated keratinocytes. AB - A procedure for transplanting cultured human keratinocytes has been developed and used successfully to treat patients with persistent leg ulcers. Shave excisions of donor skin of 1 cm2 or less were expanded in culture in 1 week to cover wounds as large as 90 cm2. The uniqueness of this system is the use of a biochemically modified surgical dressing that permits the transplantation of undifferentiated cells. Several hours after inoculation, trypsinized single cells become attached to the dressing and are ready for grafting. Seven of eight persistent stasis ulcers completely reepithelialized after application of the modified surgical dressing with undifferentiated keratinocytes. PMID- 1918460 TI - Occurrence of other malignancies in 1973 patients with basal cell carcinoma. AB - To evaluate the possible association of other malignancies with basal cell carcinoma, we reviewed 1973 consecutive patients with basal cell carcinoma. We searched the Swedish Cancer Registry for records reporting malignancies in the study population (1958-1984) and the expected number of malignancies was calculated on the basis of age- and sex-standardized incidence data. In 452 patients with basal cell carcinoma another malignancy was diagnosed. The expected number was 323 (relative risk = 1.4; 95% confidence interval = 1.3 to 1.5). A significant association with basal cell carcinoma was found in four cancer types for men and in three for women. For skin malignancies other than malignant melanoma there was more than a sixfold increased risk for men (relative risk = 6.8; 95% confidence interval = 4.8 to 9.4) and more than a threefold increased risk for women (relative risk = 3.1; 95% confidence interval = 1.4 to 5.9) during the period after the diagnosis of basal cell carcinoma. During the period before the diagnosis of basal cell carcinoma, there were also increased risks (men: relative risk = 5.0; 95% confidence interval = 3.1 to 7.5; women: relative risk = 4.0; 95% confidence interval = 1.9 to 7.4). This was in contrast to the risks of malignant melanoma. Before the diagnosis of basal cell carcinoma there was no significant increased risk of malignant melanoma but after the diagnosis there was more than a sixfold increased risk for men (relative risk = 6.8; 95% confidence interval = 4.8 to 9.4) and more than a fourfold increased risk for women (relative risk = 4.2; 95% confidence interval = 1.5 to 9.2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918461 TI - Clinical observations related to head lice infestation. AB - Living lice and eggs were found in 19% of 2643 children examined in Israel. Boys and girls were equally infested. Bite reactions, pruritus, excoriations, lymphadenopathy, and conjunctivitis were the most common signs and symptoms. Bite reactions, pruritus, excoriations, and conjunctivitis were found more frequently in infested children than in noninfested children. Lymphadenopathy, eczema, influenza, herpes, crusts behind ears, blepharitis, seborrhea, psoriasis, erythema, vitiligo, secondary infections, and scars were equally common in both groups. The sequence of the skin reactions of a volunteer to continuous exposure to lice bites was as follow: phase I, no clinical symptoms; phase II, papules accompanied by pruritus of medium intensity; phase III, wheal formation immediately after the bite, followed by a delayed papular reaction and intense itching; phase IV, papular reaction with diminished reactivity of the skin and mild pruritus. Healed bite reactions reappeared when other parts of the skin were again exposed to the lice. PMID- 1918462 TI - Immunogenetic findings in cutaneous lupus erythematosus. AB - The serologic features and histocompatibility antigen associations of 93 patients with cutaneous lupus erythematosus are reported. Of them, 37 had chronic cutaneous lupus erythematosus and 56 had subacute cutaneous lupus erythematosus. Subacute cutaneous lupus erythematosus with an annular pattern occurred in 32 patients; 24 had a papulosquamous morphology. Sixty percent of patients with annular subacute cutaneous lupus erythematosus had anti-Ro antibodies. The incidence of this antibody in the other two groups was lower. In addition, patients with annular skin lesions had significant antigen association with HLA B8 (37.5%; relative risk, 4.6) and HLA-DR3 (59.4%; relative risk, 4.3). There were no significant differences among chronic cutaneous lupus erythematosus and subacute cutaneous lupus erythematosus of the papulosquamous type and the control population for any HLA loci. Thus only patients with annular skin lesions represent a homogeneous subgroup in which there is a striking concordance of anti Ro antibodies and the HLA-B8 and HLA-DR3 phenotypes. PMID- 1918463 TI - The antiinflammatory effects of ketoconazole. A comparative study with hydrocortisone acetate in a model using living and killed Staphylococcus aureus on the skin of guinea-pigs. AB - Several reports have demonstrated the efficacy of topical ketoconazole in dermatologic conditions that are not exclusively related to fungi. Some basic pharmacologic studies have indicated effects of ketoconazole on cholesterol production in keratinocytes, on the 5-lipoxygenase enzyme, and on the metabolism of all-trans-retinoic acid in the skin. These observations have led to the hypothesis that topically applied ketoconazole may possess antiinflammatory properties. This hypothesis was tested in an animal model in which living and killed Staphylococcus aureus applied to the backs of guinea pigs resulted in inflammation with erythema and hyperkeratosis. Ketoconazole 0.5% or 2% was applied topically once daily in an ointment base, either as monotherapy or in combination with hydrocortisone acetate 1%. In addition, untreated, excipient treated, and hydrocortisone acetate-treated animals were included in the study design. All groups consisted of 10 animals that were observed and scored daily up to 3 days after the experimental therapy was stopped. In the animal model involving killed bacteria (i.e., no infection), topical ketoconazole had antiinflammatory activity comparable to that of hydrocortisone acetate. The activity of ketoconazole on the skin of animals infected with living bacteria (i.e., active bacterial infection) was superior to that of steroid therapy, which suggests some antibacterial effect of topically applied ketoconazole. The combination therapy was highly active under both conditions. These results suggest that, apart from the known antimycotic effects of ketoconazole, this molecule might also have effects against gram-positive bacteria at the high concentrations obtained after local application.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918464 TI - Determination of UVA protection factors by means of immediate pigment darkening in normal skin. AB - A method is described for screening potentially useful photoprotective agents against UVA radiation by the use of immediate pigment darkening as an end point. Threshold doses of immediate pigment darkening showed a log normal distribution and the response was found to obey dose-reciprocity at irradiance levels below 50 mW/cm2. With this procedure, several marketed sunscreens containing benzophenone 3 as the only UVA absorber were found to have poor UVA protection factors, whereas those containing combinations of benzophenone-3 and butyl methoxydibenzoyl methane or melanin were more effective. There was no correlation between the sun protection factor cited on the label and the calculated immediate pigment darkening-protection factor. PMID- 1918466 TI - Dermatologic therapy: 1990. AB - This article reviews significant therapeutic advances that have been reported in the English-language literature during 1990. Readers should review the original article in full before attempting any new experimental or controversial therapy. PMID- 1918465 TI - Trachyonychia associated with alopecia areata: a clinical and pathologic study. AB - Forty of 1095 patients (3.65%) with alopecia areata had severe nail changes that fulfilled the clinical criteria for the diagnosis of trachyonychia. Twelve of these patients had a nail biopsy. A mild to moderately dense lymphocytic infiltrate associated with exocytosis and spongiosis was detected in the proximal nailfold, nail matrix, nail bed, and hyponychium of 11 patients. One patient showed the pathologic changes of lichen planus; lichen planus of the skin developed 6 months after the nail biopsy. Immunohistochemical characterization on paraffin-embedded sections showed that the inflammatory infiltrate consisted of peripheral T lymphocytes. Immunophenotyping on frozen sections was performed in four cases. The results revealed a T4/T8 ratio of 2:1 and the presence of Langerhans cells in the nail matrix. Our results show that trachyonychia is an uncommon nail manifestation of alopecia areata. Distinctive pathologic features of mild to moderately dense lymphocytic infiltrate associated with exocytosis and spongiosis characterize trachyonychia as well as the other nail abnormalities caused by alopecia areata. The clinical association of trachyonychia with alopecia areata does not exclude that the nail abnormality can be due to other diseases such as lichen planus. PMID- 1918467 TI - Azathioprine in dermatology. AB - Azathioprine has been available for 30 years and is used in a variety of dermatologic conditions. In common with other systemic immunosuppressant drugs, it has potentially serious side effects in both the short and the long term. It has a favorable therapeutic ratio, however, and most side effects can be avoided by administering low doses for short periods. This review describes azathioprine's chemistry, drug interactions, adverse effects, and oncogenicity and then deals with its clinical applications. The well-established uses are discussed first, followed by less conventional ones. In severe, potentially fatal blistering diseases, azathioprine has an undisputed place in management. For intractable, disabling actinic reticuloid and atopic eczema, it has a smaller part to play, and its role is less clear. PMID- 1918468 TI - Sexually transmitted diseases: bacterial infections. Committee on Sexually Transmitted Diseases of the American Academy of Dermatology. AB - This update reviews the latest diagnostic and therapeutic methods regarding sexually transmitted diseases caused by bacteria. The following mucocutaneous bacterial disorders will be discussed: syphilis, chancroid, lymphogranuloma venereum, granuloma inguinale, and gonorrhea. PMID- 1918469 TI - Tinea versicolor: epidemiologic, clinical, and therapeutic aspects. AB - Age of the patient, climate, season, and local environmental factors influence the onset and course of tinea versicolor (pityriasis versicolor). A number of effective topical therapies are available. In addition, a single dose of 400 mg of oral ketoconazole eliminates the disease and can be used prophylactically in some cases to prevent recurrence. PMID- 1918470 TI - The pharmacology of methotrexate. AB - Methotrexate is a useful antimetabolite for the treatment of both benign and malignant proliferative disorders. When the pharmacokinetics and potential toxicity of this drug are understood, treatment regimens can be tailored to the underlying kinetics of the target population. With the appropriate knowledge of the importance of urinary excretion of methotrexate and factors that influence this and with the ready availability of leucovorin, toxicity can be avoided in all but the most unusual of circumstances. PMID- 1918471 TI - Abscess formation and local necrosis after treatment with Zyderm or Zyplast collagen implant. AB - The incidence, clinical presentation, pathophysiology, and possible treatment of two rare but clinically meaningful complications of tissue augmentation with Zyderm and Zyplast Collagen Implant are described. Abscesses as a manifestation of hypersensitivity to bovine collagen occur rarely (4 in 10,000 cases) and may persist for days to weeks. Periods of remission and exacerbation may occur from 1 month to more than 24 months. Localized tissue necrosis also occurs rarely (9 in 10,000 cases) after implantation and is probably the result of local vascular interruption and not hypersensitivity. The incidence varies greatly between the anatomic sites of implantation; more than half the reported cases involve the glabella. Evidence strongly suggests that the increased vulnerability of the glabellar region is due to its unique vascular distribution. PMID- 1918472 TI - Cystic verruciform xanthoma. PMID- 1918473 TI - Photopheresis in coexistent cutaneous T cell lymphoma and sickle cell disease. PMID- 1918475 TI - Multiple exostoses syndrome. PMID- 1918474 TI - Development of pseudobullous morphea and scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. PMID- 1918476 TI - Cutaneous cryptococcosis and AIDS. PMID- 1918477 TI - Annular pustular psoriasis induced by UV radiation from tanning salon use. PMID- 1918478 TI - Linear porokeratosis in a 74-year-old woman. PMID- 1918479 TI - Porokeratosis localized to the access region for hemodialysis. PMID- 1918480 TI - Puncture wound from bacteriologic culture-collecting device. PMID- 1918481 TI - Fixation in an alcohol-based preservative solution (Omnifix) PMID- 1918482 TI - Excretion of acyclovir in human breast milk. PMID- 1918483 TI - Surgical management of Hailey-Hailey disease. PMID- 1918484 TI - Concurrent epidermal changes after laser impacts. PMID- 1918485 TI - Acute hemorrhagic edema. PMID- 1918486 TI - Skin and bones. II. AB - Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. The first part of this review, published in the August 1991 issue of this JOURNAL, dealt with the first two categories; part II discusses categories 3 through 8. PMID- 1918487 TI - Pregnancy and sex steroid hormone effects on nevi of patients with the dysplastic nevus syndrome. AB - Female patients with the dysplastic nevus syndrome who were pregnant or taking sex steroid hormones were prospectively studied to evaluate the effectiveness of photography and close clinical follow-up in detecting nevus change or melanoma development. Seventeen patients, who served as their own controls, were studied during 22 pregnancies. Twenty-four patients who used oral contraceptives and seven who took hormone supplements were similarly studied. This clinical management method provided timely biopsy of changing nevi with a small number of biopsies required per patient. One melanoma occurred during pregnancy, but neither patients who were taking sex steroid hormones nor those in the control groups had melanomas. The rate of nevus change observed clinically was 3.9 times higher when patients with dysplastic nevus syndrome were pregnant than when they were not, whereas no differences were observed whether or not women took oral contraceptives or hormone supplements. The rate of histologically proven dysplastic nevi that changed was 2.0-fold higher when women were pregnant; 1.4 fold higher with the use of hormone supplements and 1.1-fold higher with the use of oral contraceptives. These preliminary data suggest pregnancy and hormone supplements may be temporally associated with an increased rate of dysplastic nevus change. PMID- 1918488 TI - Antiproliferative potential of zidovudine in human keratinocyte cultures. AB - Because the beneficial effects of zidovudine in human immunodeficiency virus infection-associated psoriasis have recently been observed, this study focused on the drug's action on the rapidly proliferating human HaCaT keratinocyte line as an in vitro model for epidermal hyperproliferation. Cultures in log growth phase were exposed to zidovudine for 2 days. Zidovudine slowed proliferation in a dose dependent fashion as evidenced by 50% inhibition concentrations of 33 mumol/L (cell number), 30 mumol/L (protein content), 0.9 mumol/L (protein synthesis), and 0.7 mumol/L (DNA synthesis). Significant (p less than 0.01) reduction of cell viability to 94.6% and 87.2%, as well as morphologic manifestations of cytotoxicity, were first evident after 2 days' exposure to maximal drug concentrations of 10 and 100 mumol/L, respectively. Control viability, assayed by trypan blue exclusion, was 98.0%. Direct cytotoxic plasma membrane injury could be ruled out by the absence of any increase in cytoplasmic lactate dehydrogenase release into supernatants at least during the 1 day of maximal dosage exposure. The drug-induced inhibition of proliferation was reversible within 7 days after a 2-day exposure to 100 mumol/L zidovudine. Two days of treatment with a 10 mumol/L dose did not alter the pattern and synthesis of keratins in vitro. Thus the known antipsoriatic efficacy of zidovudine might be explained, at least partly, by the drug's cytostatic potency. PMID- 1918489 TI - Melanocytic nevus density in Asian, Indo-Pakistani, and white children: the Vancouver Mole Study. AB - Melanocytic nevus density in 378 Asian and 68 Indo-Pakistani school children 6 to 18 years of age was compared with that in 1146 white children of the same age range. At all ages, the number of melanocytic nevi 2 mm or larger per square meter of body surface area was substantially lower in Asians and Indo-Pakistanis than in white persons. Among white persons characteristics associated with a higher risk of cutaneous melanoma in adults, that is, light skin color, a propensity to burn rather than tan in the sun, and a history of numerous or severe sunburns, are also associated with the highest melanocytic nevus density in children. Examination of these same host pigmentation and sunburn factors among Asian children revealed no association with nevus density. PMID- 1918490 TI - Simultaneous development of two cases of eosinophilia-myalgia syndrome with the same lot of L-tryptophan in Japan. AB - A newly recognized and well-described connective tissue disease, eosinophilia myalgia syndrome, is thought to relate to L-tryptophan ingestion. The suspect L tryptophan made in Japan has been distributed in Japan and in the United States. Different from many case reports of eosinophilia-myalgia syndrome in the United States, it has not been reported in Japan. We describe the first case reports of two Japanese patients. Eosinophilia-myalgia syndrome developed in these patients simultaneously, during L-tryptophan treatment by the same physician using the same lot of prescribed L-tryptophan. Furthermore, both patients had the following HLA types: HLA-Aw33(w19), -B44(12), and -DR6. These findings implicate the existence of another factor in the development of eosinophilia-myalgia syndrome in addition to the suspect L-tryptophan. PMID- 1918491 TI - Hydroxyurea therapy. AB - Hydroxyurea's place in the scheme of psoriasis therapy has diminished in recent years. Some practitioners mistakenly believe that it is used only in desperate situations, is of little or no benefit in patients unresponsive to more conventional systemic therapies, and may predispose patients to the development of secondary malignancies. Moreover, a legitimate argument against the use of this drug may be made by physicians concerned about the proliferation of systemic therapies for what is a benign, albeit unsightly, eruption. However, hydroxyurea therapy is not without advantages. It is easily dosed, relatively inexpensive, and has few contraindications or subjective side effects. In addition, patients with common systemic disorders such as hyperlipidemia, mild renal insufficiency, and cardiopulmonary disease who may not be potential candidates for other medications may be managed with hydroxyurea. PMID- 1918492 TI - Central nervous system involvement by cutaneous T cell lymphoma. AB - Central nervous system disease in cutaneous T cell lymphoma is uncommon and is usually not considered in standard therapeutic regimens. We report three patients who had cutaneous T cell lymphoma with involvement of the central nervous system and review the cases of 28 such patients reported in the literature. Potential risk factors, the reliability of various diagnostic tests, and potential therapeutic modalities are discussed. PMID- 1918493 TI - How many epidermal nevus syndromes exist? A clinicogenetic classification. AB - The term epidermal nevus syndrome is not suitable to describe an entity because there are different birth defects associated with epidermal nevi. A new classification is proposed to distinguish three well-defined syndromes, each recognizable by a different type of nevus. The sebaceous nevus syndrome and the Proteus syndrome are most likely due to autosomal lethal mutations and therefore always occur sporadically, whereas the CHILD syndrome can be transmitted from a mother to her daughter as an X-linked dominant, male-lethal trait. Moreover, the nevus comedonicus syndrome can be regarded as an entity closely related to this group of disorders. It may represent another autosomal lethal mutation that survives by mosaicism. In addition, several less well-defined phenotypes associated with epidermal nevi are reviewed. Some of them are regarded as entities in limbo. PMID- 1918494 TI - Annular erythema associated with Sjogren's syndrome: a variant of systemic lupus erythematosus. AB - We present a Burmese patient with widespread annular erythema associated with Sjogren's syndrome. Unlike previously described cases, the disease occurred in the setting of systemic lupus erythematosus. Photoprovocation testing revealed light sensitivity in the UVA range with elicitation of subacute cutaneous lupus erythematosus-like lesions. The presence of an erythema annulare centrifugum-like eruption should initiate the search for Sjogren's syndrome and systemic lupus erythematosus. PMID- 1918495 TI - Polymyositis: a manifestation of chronic graft-versus-host disease. AB - Polymyositis developed in a patient who had had bone marrow transplants for the treatment of acute myeloid leukemia. There was no previous evidence of graft versus-host disease. Polymyositis has previously been reported to be associated with graft-versus-host disease; this article suggests that polymyositis may represent its sole manifestation. PMID- 1918496 TI - Differences in clinical, serologic, and immunogenetic features of white versus Oriental anti-SS-A/Ro-positive patients. PMID- 1918497 TI - Serratia cellulitis and secondary infection of leg ulcers by Serratia. PMID- 1918498 TI - Generalized eruptive syringoma. PMID- 1918499 TI - Progressive facial hemiatrophy (Parry-Romberg syndrome) and antibodies to Borrelia. PMID- 1918500 TI - Prevalence of malignant tumors in patients with psoriasis. PMID- 1918501 TI - Dual publication and manipulation of the editorial process. PMID- 1918502 TI - Current status of the dysplastic melanocytic nevus. PMID- 1918503 TI - Ultrastructural binding site of pemphigus foliaceus autoantibodies: comparison with pemphigus vulgaris. AB - We studied in vivo binding sites of pemphigus foliaceus (PF) autoantibodies by immuno-gold labelling technique, and compared them with those of pemphigus vulgaris (PV). In early acantholytic lesions of PF, the bound antibodies indicated by 5 nm protein A-colloidal gold particles were observed on the surface of keratinocytes, with particular affinity for desmosomes and separated attachment plaques. Nondesmosomal cell surfaces were sparsely labeled with the gold particles. A similar binding pattern was seen in the epidermal sheets obtained from a PV patient utilizing the Nikolsky phenomenon. These findings indicate that both PF and PV antigen-antibody complexes are densely located on the desmosomal areas in early pemphigus lesions, suggesting the pathogenic importance of functional impairment of desmosomes by the autoantibodies. PMID- 1918504 TI - Meningoceles, meningomyeloceles, and encephaloceles: a neuro-dermatopathologic study of 132 cases. AB - Because there have been few comprehensive histopathologic studies of meningomyeloceles and related malformations, we undertook a systematic study of these lesions. One hundred and thirty two cases were obtained from our surgical pathology files; these included 38 meningoceles, 71 meningomyeloceles, and 23 encephaloceles. Tissue sections were stained with hematoxylin and eosin; special stains included trichrome, alcian blue, Fontana-Masson, Nissl, Holzer, and immunoperoxidase for glial fibrillary acidic protein. Epithelial changes included ulceration, atrophy, or nevoid hyperplasia of the epidermis, and loss of appendages. Mesodermal features included fibrous zones resembling dura, subarachnoid tissue or scar (99% of cases), increased numbers of blood vessels (83%), hypertrophy of arrector pili muscle (42%), lipoma formation (38%), and immature skeletal muscle fibers (5%) that rarely intermingled with neuropil-like matrix. The latter tissue was identified in 71% of cases and included neurons, astrocytes, oligodendroglia, and ependyma. Forty-eight percent of cases included peripheral nerve fibers or roots, and some fibers formed onion bulb or Pacinian corpuscle-like structures. Meningothelial cells were observed in 26% of cases and sometimes formed recognizable whorls. Choroid plexus was noted in 3 cases, one example showing an unusual dystrophic calcification that formed long parallel spicules. Pigmented dendritic cells were observed within zones of fibrous tissue in 10% of cases. These malformations involve complex arrangements of cutaneous, neuroectodermal, and mesodermal elements. Because they may be encountered by dermatopathologists, familiarity with the microscopic features of dysraphic lesions is essential. PMID- 1918506 TI - Eosinophils in lupus panniculitis and morphea profunda. AB - The extent of eosinophils in skin biopsy and peripheral blood specimens of patients with lupus panniculitis and morphea profunda was determined by studying 37 biopsies from 33 patients with lupus panniculitis and 55 biopsies from 53 patients with morphea profunda. Specimens from 8 (24%) of 33 patients with lupus panniculitis showed eosinophils, and 13 (25%) of 53 patients with morphea profunda had eosinophils in the subcutaneous tissue. In all cases, the diagnosis of lupus panniculitis or morphea profunda was established on the basis of other, more characteristic histologic features; the presence of eosinophils was incidental and not a diagnostic criterion. Occasional cases of lupus panniculitis or morphea profunda had numerous eosinophils. However, in most of the specimens, eosinophils were absent or observed in small numbers. Only 3% of patients with lupus panniculitis showed an increase in the number of eosinophils in the peripheral blood, whereas 47% of patients with morphea profunda had peripheral eosinophilia. The degree of hyaline necrosis in lupus panniculitis or of sclerosis in morphea profunda did not correlate with the number of eosinophils present in the biopsy specimen or peripheral blood. PMID- 1918505 TI - Rudimentary meningocele of the skin. Clinicopathologic features and differential diagnosis. AB - Although "rudimentary meningocele" (RM) or "meningothelial hamartoma" of the skin is a seemingly recently described entity, it has been included in past reports as a variant of primary cutaneous meningioma. We document our experience with four such lesions and compare the histologic and immunohistochemical features of these cases with those of seven classic meningoceles (CM) and four giant cell fibroblastomas (GCF). Although all of these entities share significant points of microscopic similarity, RM and CM are lesions composed of meningothelial cells, whereas GCF is probably of myofibroblastic origin. Rudimentary and classic meningoceles demonstrate cellular immunoreactivity for vimentin and epithelial membrane antigen, whereas the cells of GCF lack the latter determinant and may express muscle-specific actin. Our observations suggest that RM and CM represent closely related developmental malformations; however, RM becomes clinically apparent in a somewhat older patient population than CM and is not associated with major skeletal anomalies as may be found with CM. The distinction between various cutaneous meningothelial proliferations has prognostic importance, as does their separation from GCF. RM and CM are adequately treated by simple excision, whereas GCF, a probable form of fibromatosis, has the potential for local recurrence. PMID- 1918508 TI - Sequence analysis of DNA from formalin-fixed, paraffin-embedded human malignant melanoma. AB - Direct sequence analysis of in vitro amplified DNA from paraffin-embedded tissue is a promising new technique useful for detailed molecular analyses of material stored in dermatopathological archives. As only minute amounts of highly damaged DNA can be recovered from paraffin-embedded sections, sequence analysis of DNA from formalin-fixed and embedded tissue can result in less clear and readable data. We report here useful modifications that result in clear and readable sequence data. As an example, we detail the detection of a point mutation at codon 61 of the human N-ras gene in DNA from a formalin-fixed paraffin-embedded malignant melanoma specimen. This technique will be of value in many areas of molecular dermatopathology. PMID- 1918507 TI - Reactivity of fungal organisms in tissue sections using anti-mycobacteria antibodies. AB - Sixty-four cases of deep fungal infections diagnosed using PAS or silver stains and 18 control cases of sarcoidosis, M. tuberculosis and M. leprae infection were stained using commercial polyclonal antibody raised against M. paratuberculosis (MP), M. Duvalii (MD), and Bacillus Calmette-Guerin (BCG). Nine of 13 cases of sporotrichosis stained positively using anti-MP antibody only; 13 of 14 cases of histoplasmosis stained with anti-BCG, anti-MD, and anti-MP; seven cases of cryptococcosis had only focal staining of rare individual organisms within masses of negative organisms; seven of eight cases of coccidioidomycosis stained predominantly with anti-BCG and anti-MP; eight cases of aspergillus had focal (1 to 5% of organisms) staining of hyphae with anti-BCG and anti-MD; and four of 12 cases of Candida infection showed focal nonspecific staining with both antibodies and nonimmune serum. Control cases of sarcoidosis exhibited no staining with any of the three antibodies, whereas cases of mycobacterial infection showed staining of bacilli and intracellular debris with all three antibodies. PMID- 1918509 TI - Immunohistochemical studies on the localization of fetal antigen 2 (FA2), laminin, and collagen type 4 in basal cell carcinoma. AB - The localization of fetal antigen 2 (FA2), a recently described basement membrane (BM) associated antigen, was studied by immunohistochemical techniques in 21 basal cell carcinomas (BCC). In both superficial and infiltrating BCC, FA2 was located in a broad diffuse band around the tumor elements and in close contact with the BM. Compared to normal skin, a more extensive distribution of FA2 was seen in BCC. In the infiltrating BCC, FA2 staining was also present in the interstitial stroma between the tumor islands. FA2 was absent in areas with inflammatory cell infiltrates and elastoid degeneration. Epithelial and tumor cells were FA2 negative. The distribution of FA2 was clearly different from that of laminin and collagen type 4. Collagen type 4 and laminin were present as a continuous linear band corresponding to the BM surrounding the tumors. The close contact to the BM and the increased content of FA2 in the reactive stroma around BCC suggest that FA2 is involved in the matrix and/or BM changes taking place during tumor growth and invasion. PMID- 1918510 TI - Cystic fibroepithelioma of pinkus. AB - A 59-year-old female with a cystic fibroepithelioma of Pinkus is presented. The clinical and histopathological features of this unusual variant of basal cell carcinoma are discussed. PMID- 1918511 TI - Extraction of plasma triacylglycerols by the mammary gland of the lactating cow. AB - The fatty acid content of triacylglycerols (TG) in arterial and mammary venous blood plasma has been analysed in five cows that were close to peak lactation. The fatty acids in arterial TG were extracted by the mammary gland in amounts 14:0 less than 16:0 less than 18:0 and 18:0 greater than 18:1n - 9 greater than 18:2. The difference of extraction between palmitate and stearate was similar in different TG species. The fatty acid 18:1n - 7, which was largely the trans isomer, was extracted more than 18:1n - 9. Significant amounts of phytanic acid were acylated in plasma TG, but not extracted by the mammary gland. PMID- 1918512 TI - Elevation of bovine serum C-reactive protein and serum amyloid P component levels by lactation. AB - C-reactive protein (CRP) and serum amyloid P component (SAP), which are known to increase in sera from humans and many other animals with acute inflammation caused by infection, toxic drug administration or injury, were previously purified from bovine serum. These serum levels were determined by enzyme-linked immunosorbent assay (ELISA) using specific antiserum to bovine CRP or SAP which was prepared by immunizing rabbits and goats with each purified protein. Among 68 healthy Holstein cows, 45 non-lactating cows had levels of CRP and SAP of 20.6 +/ 1.4 and 27.6 +/- 1.3 micrograms/ml respectively; 23 lactating cows had higher levels of CRP and SAP (76.0 +/- 13.6 and 38.3 +/- 5.5 micrograms/ml respectively). In the latter group, there was a high correlation between milk yield and serum CRP levels (P less than 0.001). From these observations, it was assumed that lactation might stimulate CRP synthesis rather than SAP synthesis in bovine liver as an acute phase reaction, and that CRP might be called a lactation associated protein. PMID- 1918513 TI - Influence of milk flow rate on new intramammary infection in dairy cows. AB - In a series of short-term experiments cows were subjected to exaggerated bacterial challenge and accentuated milking machine conditions known to predispose to new mammary infection. The incidence of new intramammary infection was significantly greater in quarters with peak flow rates greater than 1.6 kg/min whether they were exposed to impacts (P less than 0.05) or milking without pulsation (P less than 0.001). The infection rates were much lower (P less than 0.001) in quarters milked with 'pulsation and shields' to protect against these two machine factors. Despite this, quarters with peak flow greater than 1.6 kg/min still showed a 12-fold increase in mastitis incidence compared with quarters with peak flow less than 0.8 kg/min. Rates of milk flow have increased dramatically in the last 40 years through selection and breeding: whole udder peak flow rates in heifers have doubled from 1.9 to 3.8 kg/min. Increased emphasis, therefore, should be placed on hygiene, husbandry and milking techniques to minimize bacterial numbers at teat ends to control mastitis as the drive for higher flow rate and yield make cows increasingly more susceptible to infection. These results suggest that the benefits of reduced infection rate from mastitis control are significantly underestimated since animals are now considerably more susceptible than 40 years ago. PMID- 1918514 TI - Adolescent coping: the different ways in which boys and girls cope. AB - In order to investigate the ways in which boys and girls cope with their concerns, 650 Year 11 and Year 12 students from seven post-primary schools in Melbourne, Australia were asked to describe how they cope with the main concerns in their lives. In addition to elicitation of spontaneous responses, a modified form of the Ways of Coping Checklist (Folkman and Lazarus, 1980; 1985b) was also administered to obtain an assessment of students coping strategies. Clear differences were found between the ways in which boys and girls cope. Girls seek more social support and generally are more likely than boys to focus on relationships. They also employ more strategies related to hoping for the best and wishful thinking. The question of how boys and girls can develop their coping repertoire so as to increase the adaptability of their responses in difficult situations is also addressed. PMID- 1918515 TI - The challenge of deliberate self-harm by young adolescents. AB - This paper describes a model of crisis intervention to families of adolescents below the age of 16 who deliberately harm themselves and summarizes the premises which guide our practice. The adolescent's "overdose" is understood as an attempt to resolve relationship conflicts and so the initial interview aims to explore the predicament for the adolescent and the family and decide what further help may be required. Verbatim extracts from one session illustrate this process. PMID- 1918516 TI - Self-report measures of obsessionality, depression and social anxiety in a school population of adolescents. AB - The results are reported for a non-clinical school population of 252 adolescent subjects, aged 13 to 15 years, responding to the Maudsley Obsessive-Compulsive Inventory (MOCI), the Children's Depression Inventory (CDI) and the List of Social Situation Problems (LSSP). The scales intercorrelated significantly but appear to measure different aspects of self perception. No significant age or gender effects emerged in any. The results obtained are compared with those of previous studies and the use of the MOCI in adolescent populations discussed. PMID- 1918517 TI - Ethnic differences in adolescent self-poisoning: a comparison of Asian and Caucasian groups. AB - A study of self-poisoning in 25 Asian and 25 Caucasian adolescents is presented. Cultural conflicts were the most important factors in the parasuicidal behaviour of Asian children, whereas a variety of factors accounted for the parasuicidal behaviour of Caucasians with a predominance of a disrupted family background. There was little difference in the type of poisoning and the degree of pre planning between the two groups. PMID- 1918518 TI - Male and female patterns in the discovery of sexuality during adolescence. AB - The present paper attempts to analyse the various factors which influence adolescents strategies in their efforts to cope with the problems related to pubertal and sexual development: the physiological changes, the social pressures engendered by family and cultural environment, and the personal meanings young boys and girls attribute thereto. The data came from 603 questionnaires and 60 interviews performed on Italian adolescents (both males and females, students and non-students) on the following issues: the awareness of physical maturation in the same and opposite sex; the significance of heterosexual relationships; the motivation for early sexual experiences; and their effects on personal identity. Significant differences concerning sex and level of schooling emerged with regard to the elaboration of the subject's psychosexual identity, motivation in the choice of partner and the precocity in the onset of sex life. PMID- 1918519 TI - Relations between young adults and their parents. AB - Young adults' relationships with mothers and fathers are compared in a survey of undergraduates. Both men and women report spending more time with mothers than fathers. They indicate receiving more positive treatment from mothers and experiencing more positive emotion and closeness with them than fathers. Correlations between perceptions of treatment and experience of emotion are moderately strong, as are those between treatment/emotion and intentions to model parents. Young adults express greater certainty in using mothers than fathers as models in child-rearing, which is associated with experiencing more positive treatment and emotion with them. Since they report no more negative treatment from fathers than from mothers, their closer connections with mothers are probably due to a more positive dynamic with mothers rather than a negative dynamic with fathers. These results are consistent with previous findings that individuation and well-being in adolescence are facilitated by close, positive relationships with parents rather than distancing ones. PMID- 1918520 TI - Adolescent and older mothers' interaction patterns with their six-month-old infants. AB - Children of adolescent mothers suffer more physical, intellectual, and emotional difficulties than do other children. In order to gain a better understanding of the differences, the interaction patterns of adolescent mothers and non adolescent mothers interacting with their young infants were compared. One hundred adolescent mothers and 29 married primiparous non-adolescent mothers were observed interacting with their six-month-old infants during a feeding episode and a play episode. All of the mothers had a high school education or less. During feeding, the adolescent mothers demonstrated less expressiveness, less positive attitude, less delight, less positive regard, fewer vocalizations, and a lower quality of vocalizations than non-adolescent mothers. During play, the adolescent mothers demonstrated less inventiveness, less patience, and less positive attitude than the non-adolescent mothers. These results extend and strengthen what is known about adolescent mothers patterns of interaction with their young infants. PMID- 1918521 TI - Functional implications resulting from disruption of the calcium-binding loop in bovine alpha-lactalbumin. AB - The strong calcium-binding site of alpha-lactalbumin comprises the carboxylate side chains of aspartic acid 82, 87, and 88 and the carbonyl oxygens of residues 79 and 84. A single methionine residue was selectively modified by controlled CNBr cleavage to yield homoserine at position 90. The CNBr-cleaved alpha lactalbumin lost the ability to bind calcium strongly as monitored by intrinsic fluorescence, electrophoretic mobility, atomic absorption, and x-ray fluorescence. Remarkably, the modified protein was still competent in lactose biosynthesis, although activity was reduced to 1/40th that of the native form of the protein. Although the strong calcium-binding site was destroyed as a result of the cleavage of the calcium-binding loop, a secondary calcium site was retained that directly affects a rate enhancement of lactose biosynthesis when saturated, resulting in approximately a two- to threefold increase in rate at 1 mM CaCl2 with an activation equilibrium constant of 350 +/- 40 microM. PMID- 1918522 TI - Identification of kappa-casein genotype in Holstein sires: a comparison between analysis of milk samples from daughters and direct analysis of semen samples from sires by polymerase chain reaction. AB - Two different methods were used to determine kappa-casein genotypes of Holstein sires. In the earlier procedure, genotypes of sires were deduced by analyzing frequency distribution data of kappa-casein variants obtained through typing of milk samples from daughters by electrophoresis. The second method involved direct analysis of DNA obtained from semen samples of the sires. The polymerase chain reaction was used to amplify a 99-bp region from the kappa-casein gene that contains nucleotide substitutions that are diagnostic of variants A and B. Identity of the amplified product was confirmed by sequencing. Results obtained by both methods of genotyping were similar. For the 42 sires that were analyzed by both methods, the distribution of kappa-casein genotypes were 31 AA, 11 AB, and 0 BB. The frequency of B allele for kappa-casein in the sire population studied was lower than in larger Holstein cow populations. Due to the high demand for kappa-casein B milk by the dairy industry, it might be advantageous to increase this allele in the dairy cattle population by identifying sires with homozygous kappa-casein B and using them more frequently as service sires. PMID- 1918523 TI - Modulation of bovine mononuclear cell proliferation during physiological transitions of the mammary gland. AB - Mammary secretions and blood were collected from five primiparous Holstein cows 14 d following cessation of milking and 14 d prior to parturition for preparation of serum and mammary secretion skim fractions. Mammary secretions and blood were collected from the same animals 15 to 18 d following cessation of milking and 2 to 13 d prior to parturition for isolation of mononuclear cells. Effects of serum on mammary gland mononuclear cell proliferation and skim fractions from mammary secretions on blood mononuclear cell proliferation were evaluated. Mononuclear cell proliferation was evaluated in a mitogen-induced lymphocyte proliferation assay and in a mixed leukocyte assay. Proliferative responses of blood and mammary gland mononuclear cells did not vary significantly between the two time periods evaluated. Mammary secretion skim fractions obtained at both time periods significantly suppressed blood mononuclear cell proliferation. In contrast, exogenous serum enhanced mammary gland mononuclear cell proliferation in response to mitogens and allogeneic cells. Ability to enhance in vitro proliferation of mammary mononuclear cells isolated during physiological transitions of the mammary gland may suggest the potential for enhancing mammary mononuclear cell proliferation in vivo to reduce incidence of new intramammary infections at times when the mammary gland is highly susceptible. PMID- 1918524 TI - Effect of bovine skim milk and whey on monocyte function. AB - Previous studies have documented the ability of bovine milk to inhibit lymphocyte proliferation in response to mitogens. It is not known whether inhibition of lymphocyte proliferation is mediated through the action of monocytes. To address this question, we examined the ability of bovine skim milk and whey to affect monocyte function with emphasis on expression of major histocompatibility class II antigens and production of interleukin-1 by monocytes. Data showed that expression of major histocompatibility complex class II molecules and production of interleukin-1 by monocytes were not altered when monocytes were cultured in the presence of bovine skim milk or whey. Thus, it is unlikely that the suppressive effect of milk on lymphocyte proliferation could be mediated through alterations in the expression of major histocompatibility class II molecules or in production of interleukin-1 by monocytes. The role of other monocyte antigens or secretory products, however, should also be evaluated. PMID- 1918525 TI - Effects of premilking teat preparation on spores of anaerobes, bacteria, and iodine residues in milk. AB - Premilking teat preparations using individual paper or cotton towels for either 6 or 20 s to reduce bacteria and iodine residues from teat surfaces were determined through Latin square designs applied to 50 cows. A cotton towel used for 20 s was most effective in cleaning teats, probably because of the physical structure of the towel, physical action on teat surface, and scrubbing of the teat ends. Premilking teat preparation of 6 s was inadequate to clean teats and to avoid iodine residues in milk. Teat end erosions increased iodine residue in milk. Two days after a treatment period, iodine content in milk from iodophor-dipped groups was similar to that of the undipped control group. Against our expectation, teat dipping with a .25% iodophor teat dip caused higher iodine residue in milk than a .50% iodophor teat dip. Differences in formulations and inert ingredients of iodophor teat dips indicate a need for further studies. PMID- 1918526 TI - Effect of milk yield on relationship between bulk milk somatic cell count and prevalence of mastitis. AB - The possible dilution effect of increasing milk yield on bulk milk SCC was studied in a field trial. Data on breed distribution, numbers of cows, average milk yields, average bulk milk SCC, and estimated prevalences of mastitis were available for 15,514 Swedish dairy herds. The overall mean of herd prevalence of mastitis, as estimated by the definition employed, was 26.7%, and the overall mean of the geometric average of bulk milk SCC was 204,000 cells/ml. Correlations between prevalence of mastitis and average bulk milk SCC ranged between .53 and .77, and geometric averages were only marginally more correlated to prevalence of mastitis than were arithmetic averages. The average herd prevalence of mastitis was found to increase, within bulk milk SCC level, as milk production increased. The regression coefficients of average milk yield on bulk milk SCC, estimated conditionally on mastitis prevalence, show that the bulk milk SCC decreased by 11.1% for each increase in the milk yield of 1000 kg of FCM. This implies that part of the decrease in average bulk milk SCC achieved during recent years may be an artifact due to the concurrent increase in milk production. PMID- 1918527 TI - Whole blood and plasma amino acid uptakes by lactating bovine mammary glands. AB - The objective of the experiment was to determine the contribution of red blood cells to transport of individual amino acids to lactating bovine mammary glands. Blood samples were collected from coccygeal and subcutaneous abdominal veins of 21 lactating Holstein cows on d 35, 70, 105, and 126 of lactation. Samples were collected every 20 min for 12 h. Subsamples of whole blood and plasma were pooled by hour and day. Hourly plasma samples and daily whole blood and plasma samples were analyzed for amino acid concentration. Plasma glutamate concentration was stable throughout the 12-h collection period, indicating that sample collection did not perturb amino acid homeostasis. Therefore, data from pooled daily samples were used for subsequent comparisons. Whole blood arteriovenous differences of phosphoserine, aspartate, glutamate, hydroxyproline, phosphoethanolamine, serine, asparagine, glycine, glutamine, taurine, histidine, citrulline, threonine, alanine, beta-aminoisobutyrate, carnosine, arginine, proline, alpha aminobutyrate, tyrosine, valine, methionine, cystine, isoleucine, leucine, phenylalanine, tryptophan, ornithine, and lysine differed significantly from plasma arteriovenous differences. Uptakes of individual amino acids from plasma were poorly correlated with uptake from whole blood. These data clearly indicate that uptake data derived from plasma do not adequately represent whole blood amino acid uptake. PMID- 1918528 TI - Body temperature and respiratory rate of lactating dairy cattle under field and chamber conditions. AB - A coordinated field and chamber experiment assessed breed, sire, and cow differences in body temperatures and respiratory rates. During each of 4 yr, 10 lactating Ayrshire, Guernsey, Holstein, and Jersey cows, 40 animals per yr, were observed in the field on 10 d when the air temperature approached 32 degrees C. For the first 3 yr, each cow also was exposed in a controlled atmospheric chamber at 40 degrees C and 34 mm Hg vapor pressure. Significant breed differences were found for body temperature and respiratory rate. The order of tolerance to hot conditions was Jersey, Guernsey, Ayrshire, and Holstein both in the field and chamber. Significant sire differences, interpreted as genetic, were found for the field measures but not in the chamber. Repeatability of individual field observations for a cow on different days in a year ranged from .38 to .55. Correlations between the average of 10 observations for a cow in the field during a year and the chamber evaluation were positive but lower than the repeatability values. Correlations of ambient temperature with body temperatures and respiratory rates were highest; those for radiation were next, followed by vapor pressure and air movement. PMID- 1918529 TI - Effect of selenium and reducing agents on in vitro immunoglobulin M synthesis by bovine lymphocytes. AB - A series of experiments was conducted to evaluate the effects of inorganic and organic forms of Se with or without reducing agents on in vitro IgM production by bovine lymphocytes. Peripheral mononuclear cells were isolated from nonlactating Jersey cows fed a diet with adequate Se. Cells were stimulated with pokeweed mitogen and, in addition, were cultured with various Se compounds at a concentration of 100 ng Se/ml. Mercaptoethanol (50 microM) and glutathione (1 mM) were included in cultures of cells stimulated by pokeweed mitogen with and without inorganic Se. Sodium selenite was less effective than selenomethionine and selenocystine in augmenting pokeweed mitogen-induced Ig synthesis. The addition of mercaptoethanol to pokeweed mitogen-stimulated control cultures enhanced in vitro IgM production, whereas the addition of glutathione had a negligible effect, but addition of either in combination with sodium selenite dramatically depressed IgM production. These results suggest that Se in inorganic or organic forms enhances B-cell function in vitro. PMID- 1918530 TI - Effects of ketones, acetate, butyrate, and glucose on bovine lymphocyte proliferation. AB - Blood leukocytes from age-matched heifers were used to determine effects of ketones, acetate, butyrate, and glucose on in vitro lymphocyte proliferation. Lymphocytes stimulated with concanavalin A, phytohemagglutinin-P, or pokeweed mitogen were cultured in the presence or absence of beta-hydroxybutyrate, acetoacetate, acetone, acetate, butyrate, and glucose. Only supraphysiological levels of beta-hydroxybutyrate inhibited proliferation in cultures of mitogen stimulated lymphocytes, whereas mixtures of beta-hydroxybutyrate and acetoacetate at levels seen in severe ketosis stimulated concanavalin A and phytohemagglutinin P-driven proliferation. Because acetoacetate was a lithium salt, lithium chloride served as a negative control. Results suggest the enhanced proliferation by cultures containing lithium acetoacetate was due to lithium, not acetoacetate. Butyrate (at concentrations greater than seen in bovine plasma) and acetate at normal levels inhibited proliferation. Concanavalin A- and pokeweed-mitogen driven proliferation was greater in cultures containing lower glucose levels, but acetate added to cultures containing low glucose inhibited concanavalin A stimulated proliferation. Proliferation by pokeweed mitogen-stimulated cultures containing acetate, beta-hydroxybutyrate, and acetoacetate was suppressed at the lower concentrations of glucose tested. In conclusion, ketones, butyrate, and glucose at concentrations occurring in vivo had minimal effects on bovine lymphocyte proliferation in vitro. Levels of acetate associated with ketosis suppressed lymphocyte function and may alter immune responsiveness in vivo. PMID- 1918531 TI - A compartmental model to analyze ruminal digestion. AB - In contrast to digestion models that include a discrete lag phase, a compartmental digestion model was proposed. It assumed the existence of a lag compartment and a digestion compartment. Substrate present in the digestion compartment was subject to first-order kinetics digestion. Flow of substrate from the lag compartment to the digestion compartment was proposed to be a first-order process and likely was affected by hydration of substrate, bacterial attachment, and colonization. The proposed model was compared with models that assumed the existence of a discrete lag phase. Parameter estimates for these models were obtained either through logarithmic transformation of data or nonlinear regression. Statistically, there was no difference between the compartmental model and the nonlinear model with a discrete lag phase. Differences in parameter estimates between these two models were small. Residual mean squares were higher for the logarithmically transformed models. Differences in parameter estimates between these models and the compartmental model depended on the structure of the experimental data. In a number of cases, the nonlinear parameters of the compartmental model converged to the same value, resulting in a different interpretation of the model. Residual mean squares for predicting rate of disappearance were lowest for the compartmental model. PMID- 1918532 TI - An assessment of absorbable lysine requirements in lactating cows. AB - Two experiments were conducted to ascertain lysine required for maintenance and milk production in lactating dairy cows. Multiparous Holstein cows fitted with abomasal cannulas were utilized in a replicated 3 x 3 extra-period Latin square design and infused with 0, 45, or 90 g of L-lysine-HCl daily (Experiment 1). In Experiment 2, 12 cows were utilized in a 5 x 5 Latin square design (with 2 replacement cows) and infused with 0, 22.5, 45, 90, and 180 g of L-lysine-HCl daily. Cows were housed in comfort stalls, milked at 0600 and 1700 h, exposed to a 16:8 h light:darkness cycle, and fed for ad libitum intake a 15.7% CP diet formulated to contain approximately 75% of dietary protein from corn-based feed ingredients. Milk yield was not affected in Experiment 1, but milk production increased linearly with lysine infusion level in Experiment 2. A linear response in daily yield of milk protein to lysine infusion was observed in both experiments. As lysine infusion increased, coccygeal plasma lysine concentrations tended to increase in Experiment 1, but in Experiment 2 free lysine increased linearly and quadratically in coccygeal plasma and increased linearly in plasma from the subcutaneous abdominal vein. The quadratic response in plasma free lysine (Experiment 2) suggested that lysine was the limiting AA for milk production from the composite protein flow to the small intestine. Using break point analysis of plasma free lysine, it was estimated that the additional amount of abomasal lysine required to satisfy requirements was 64 g/d in cows producing about 30 kg of milk daily. Although additional lysine above microbial and undegraded intake protein lysine flow stimulated milk protein production, conversion efficiency to milk protein lysine was low. PMID- 1918533 TI - Use of nitrogen-15 determinations of purine nitrogen fraction of digesta to define nitrogen metabolism traits in the rumen. AB - A method for direct purine N isolation and determination was modified from the method of Zinn and Owens for rapid determination of purines. By this method, N derived from purines in digesta was measured and collected for 15N determinations. Measurements of purine N in 33 samples of ruminal contents and duodenal digesta of sheep and goats were compared with purine determinations in the same samples. The results showed that essentially all the N in the purines that could be isolated by the Zinn and Owens procedure also could be detected by N isolation and determination. Determinations of 15N in the NH3 N, NAN, and purine N fractions in a continuous culture in vitro showed significant differences in the 15N enrichment curves between diets based on either roasted or raw soybean meal. PMID- 1918534 TI - The response of lactating dairy cows to increasing levels of whole roasted soybeans. AB - Twenty-four Holstein cows, including four primiparous and four ruminally cannulated, were in replicated 4 x 4 Latin squares with 21-d periods to determine the effects of feeding level of whole roasted soybeans on lactation performance and rumen function. Cows were fed rations containing a 50:50 forage:concentrate ratio with 0, 12, 18, or 24% of diet DM as whole roasted soybeans. Rations contained 16.8, 16.9, 18.6, and 19.7% CP and 1.68, 1.71, 1.72, and 1.74 Mcal NEL/kg DM, respectively. Milk production and milk fat percentages for diets containing 0, 12, 18, or 24% whole roasted soybeans were 34.9, 37.5, 38.5, and 38.8 kg/d and 3.23, 3.20, 3.32, and 3.37%, respectively. Milk protein percentage was depressed at all levels of whole roasted soybeans. Ruminal pH, VFA molar percentages except valerate, and DM disappearance of forage from dacron bags did not differ among treatments. Responses were similar among primiparous and multiparous cows. Results suggest benefit from feeding whole roasted soybeans at levels up to 18% of ration DM without adversely affecting DMI, milk fat, or rumen fermentation. PMID- 1918535 TI - Feeding hydrogenated fatty acids and triglycerides to lactating dairy cows. AB - Effects of feeding hydrogenated tallow fatty acids and triglycerides to lactating dairy cows were studied using five primiparous Holstein cows in a 5 x 5 Latin square design. A control diet with no supplemental fat and diets containing either hydrogenated tallow fatty acids or triglycerides at 2 and 5% levels were fed for ad libitum intake. Diets were isonitrogenous but not isocaloric. Each treatment period consisted of 28 d; the last 14 d were used for data collection. Fat-supplemented diets had no effects on DM intake, milk fat percentage, milk protein percentage, and BW compared with the control diet. Energy intake and milk yields were higher for cows fed fat-supplemented diets. Adding fatty acids to diets increased milk fat percentage above that in milk from cows fed triglyceride diets. Apparent digestibilities of DM and OM were lowered by the addition of fat, mainly in response to fatty acid additions. Feeding fatty acids reduced ash digestibility compared with feeding triglycerides, and NDF digestibility also tended to be lower for cows fed fatty acid diets. Fat addition to diets reduced fatty acid digestibility; digestibility of added fat averaged 37.7%. Although of similar saturation, the triglyceride supplement was more ruminally inert than the fatty acid supplement. Esterification and degree of saturation are features of importance when processing tallow for use in ruminant diets. PMID- 1918536 TI - Total lactational response to added fat during early lactation. AB - The theory that feeding cows additional fat during early lactation will result in greater total lactational production and improved reproductive efficiency was evaluated using 305-d lactational data from 94 cows fed control diets and 96 cows fed additional dietary fat during wk 4 through 16 postpartum. Added fat in diets was supplied by oilseeds, either soybeans or sunflowers, in previously reported studies. Milk yield during wk 4 through 16 postpartum was 2.8% higher for cows fed added fat. Total lactational yield was increased 3.6% for cows fed additional fat in early lactation; 71% of the additional milk production occurred after discontinuing the feeding of additional fat. Percentages of milk fat and protein were lower when cows were fed added fat and remained lower for the remainder of the lactation. Days to first breeding, days open, and services per conception were not reduced by feeding added fat during early lactation. Milk production and persistency for the entire lactation were increased by feeding additional fat during early lactation, but changes in reproductive efficiency were not detected. PMID- 1918537 TI - Hormonal responses to bovine somatotropin and dietary protein in early lactation dairy cows. AB - The effects of bST injection and dietary protein level on blood hormone and metabolite concentrations were examined in four mature Holstein cows in a double crossover design. Cows were assigned at d 5 to 9 postpartum to receive daily injections of either a control (saline) solution or 20.6 mg of bST. Four 3-wk periods were used during which one cow from each group was fed a medium protein diet (17.1% CP), and the other received a high protein diet (23.6% CP). Injections of bST or control solutions began on d 0 of the second period. Intakes of DM were not influenced by dietary protein or bST injection. Milk yield tended to increase with increased CP level but was not affected by bST injection. Based on the rate and extent of decline in milk production after cessation of bST injection, the cows assigned to bST had lower milk production potential than control cows. Thus, the effect of bST injection apparently was to enhance milk yield to levels similar to those of controls. There were no significant CP level or bST injection effects on glucose, FFA, somatostatin, or somatotropin concentrations. Glucagon concentrations were higher in bST-treated cows. Concentrations of insulin-like growth factor-I were increased with increased CP level and also with bST injection. Significant effects of days on bST were observed for insulin, insulin-like growth factor-I, glucose, and FFA. Cows given bST injections and producing equal amounts of milk as control cows did not show major physiological differences in hormones and metabolites with the exception of insulin-like growth factor-I. PMID- 1918538 TI - Recombinant bovine somatotropin with lactating cows fed diets differing in energy density. AB - Sixty-four Holstein cows (32 primiparous) were assigned randomly at parturition to one of two diets differing in forage:grain ratio and were further assigned to either control or treatment with recombinant bST. A full lactation study was conducted. Total mixed rations consisted of alfalfa silage, high moisture ear corn, soybean meal, and vitamin and mineral supplements. Percentages of forage in the diet (dry basis) for the high and medium energy diets were wk 1 to 12, 38.2 and 58.2; wk 13 to 26, 48.2 and 68.2; and wk 27 to 44, 68.2 and 88.2. Injection of a saline placebo or 20.6 mg/d per cow of bST started at wk 13 and stopped at wk 43 of lactation. Administration of bST increased 305-d milk yield by 19.9 and 18.3% for multiparous cows fed high and medium grain diets and by 13.0 and 5.9% for primiparous cows fed the same diets. Body weight gain during lactation tended to be lower for cows treated with bST, and body condition scores were significantly lower for those treated with bST and fed the medium energy diets. Daily injection of bST did not change concentrations of glucose or urea in blood or beta-hydroxybutyrate in plasma. Multiparous cows had a transitory increase in plasma FFA concentration immediately after bST treatment started. Milk composition, health, and reproductive parameters observed were not adversely affected by bST administration. Cows fed low energy diets during bST administration in the first lactation did not produce as much milk as controls when compared during the first 10 wk of their second lactation. PMID- 1918539 TI - Evaluation of sometribove in a prolonged-release system in lactating dairy cows- production responses. AB - Primiparous (n = 105) and multiparous (n = 136) Holstein cows were used to evaluate efficacy of sometribove (n-methionyl bovine somatotropin, bST) in a dose titration study. Cows were fed TMR for ad libitum intake, were milked twice daily, and were allocated randomly within parity (1 vs. 2+) to treatments of 0, 250, 500, or 750 mg bST/14 d in a prolonged-release formulation. Subcutaneous injections commenced 60 +/- 3 d postpartum and continued throughout lactation. During a standardized treatment period of 252 d, treatment with increasing dosages of bST increased 3.5% FCM yield in a dose-dependent manner for both primiparous (2.5 kg/d, 10.2%; 3.5 kg/d, 14.3%; and 5.9 kg/d, 24.1%) and multiparous cows (3.1 kg/d, 12.1%; 3.9 kg/d, 15.2%; and 6.8 kg/d, 26.5%). Milk content of fat, protein, lactose, ash, Ca and P, and SCC were not affected by treatment. Over the 252-d treatment period, voluntary intake of energy was increased in bST-treated cows such that BW gain, body condition score, and net energy balance did not differ among treatment groups. Productive efficiency (milk per unit NEL intake corrected for BW change) over the treatment period was significantly increased in a dose-dependent manner for multiparous cows (4.1, 6.8, and 11.0%). Results demonstrated that bST administered in a prolonged release formulation was efficacious in enhancing milk production and feed efficiency. PMID- 1918540 TI - Near infrared spectroscopic analysis of forage samples digested in situ (nylon bag). AB - The objective was to investigate the feasibility of using near infrared reflectance spectroscopy to determine the composition of samples generated in situ. Five alfalfa and five orchardgrass hays of differing maturities were incubated for 0, 6, 24, 48, and 72 h (Experiment 1) or for 0, 2, 4, 8, 12, 24, 48, and 96 h (Experiment 2) in rumen-fistulated, lactating cows, using nylon bags. After washing to remove rumen contents, samples were analyzed using a nonrotating circular cell in a scanning monochromator. All samples then were dried at 55 degrees C and analyzed for CP and ADF by wet chemistry and rescanned in the dry state. The degree of DM digestion of the original sample was calculated from duplicate bags. Results for spectral analysis of dried samples (Experiment 1), with one-half the samples for validation, were typical of results found for dry forages. The results for scanning wet samples were less accurate than for dry ones. Analysis of samples from Experiment 2 by equations developed in Experiment 1 often resulted in extremely large biases, but these were corrected by including six samples of each forage from Experiment 2 in the calibration set (from Experiment 1) and redeveloping the equations. Although it is possible to use near infrared reflectance spectroscopy to determine the composition of wet samples generated in situ, results are more accurate if the samples are scanned after drying. PMID- 1918541 TI - Chemical drying agents for alfalfa hay: effect on nutrient digestibility and lactational performance. AB - Effects of chemical drying agents for hay on plasma profile, lactational performance, and nutrient digestibility by cows were studied. First-cutting alfalfa (late bud) was harvested as hay and treated when cut by applying untreated control, a commercial drying agent (7.64 kg/ha), or a mixture of active ingredients, potassium carbonate and sodium carbonate (7.47 kg/ha). Six multiparous Holstein cows (120 to 150 d postpartum) were fed diets (two cows per treatment) containing 55% hay and 45% concentrate (DM basis) in a balanced two period changeover design. Plasma profiles were similar for all cows, regardless of hay treatment. There were no differences in milk yield, milk fat, or milk protein percentages for control, drying agent, or mixture. Intake of DM was not different among treatments. Apparent digestibilities of DM, OM, CP, NDF, and ADF were not different among treatments. Treatment of alfalfa hay with chemical drying agents did not alter plasma profile, milk production, or nutrient digestibility in midlactation cows. PMID- 1918542 TI - Effect of dietary forage:grain ratio on blood constituents in dairy cows. AB - Forty-nine primiparous and 44 multiparous lactating Holstein cows were used to study the effect of five dietary forage: grain ratios on blood constituents. Blood samples were collected in wk 2, 3, 4, 6, 8, 12, and 16 of lactation and were analyzed for glucose, urea, beta-hydroxybutyrate, and FFA. Increasing the percentage of forage in the diet decreased blood glucose concentration. Glucose levels were low at the beginning of lactation and increased as DMI increased. Increasing percentage of forage in the diet did not affect blood urea concentration. Increasing forage in the diet from 38.2 to 98.2% increased beta hydroxybutyrate concentrations threefold during the first 4 wk of lactation in both primiparous and multiparous cows. The concentration of plasma FFA was higher in all the treatments at the beginning of lactation and decreased as lactation advanced. Dietary forage:grain ratio did not affect plasma FFA. PMID- 1918544 TI - Effects of rearing diet, age at freshening, and lactation feeding system on performance. AB - This two-phase trial involved 83 Holstein heifers. The rearing phase consisted of two diets (alfalfa silage plus corn grain for ad libitum intake vs. corn silage plus urea for ad libitum intake) and two breeding age groups (13 vs. 16 mo). The lactation phase compared the above treatments plus two lactation feeding systems: concentrate fed individually to production versus a TMR. The heifers were assigned randomly to the rearing phase at 7 wk of age and fed their respective diets until 14 d prepartum. They were placed on preassigned lactation diets 14 d prepartum and remained on the lactation phase for 550 consecutive d. Daily gains and height at the withers were similar between forage groups during the first half of the rearing phase; in the second half, the heifers fed alfalfa silage were taller at the withers. Those fed corn silage consumed less DM and CP throughout the rearing phase and gained more BW than the heifers fed alfalfa in the latter half. There were no differences in daily gain or DMI between the breeding age groups. In the lactation phase, the group fed alfalfa for ad libitum intake consumed more DM and gave more milk during the first 90 d of lactation than heifers fed corn silage. However, after 90 d the difference in cumulative milk production was not significant. There were no differences in milk production. FCM, or DMI between breeding age groups. The cows fed concentrate consumed more DM and gave more milk during the first 90 d of lactation. By 550 d, there were no differences. Feeding high levels of corn silage can cause heifers to have lower DMI in early lactation. These differences tend to disappear during the second lactation. PMID- 1918543 TI - Milk production response to dietary forage:grain ratio. AB - Forty-four multiparous and 49 primiparous Holstein cows were assigned randomly at parturition to one of five diets differing in forage:grain ratio and studied for the entire lactation for effects of diet on milk production and milk composition, body condition, BW gain, health, and reproductive performance. Total mixed rations fed once daily consisted of alfalfa silage, high moisture ear corn, soybean meal, vitamins, and minerals. Percentages of forage in the diet (dry basis) for treatments 1 to 5 were postpartum wk 1 to 12 (38.2, 48.2, 58.2, 68.2, and 98.2); wk 13 to 26 (48.2, 58.2, 68.2, 88.2, and 98.2); and wk 27 to 44 (68.2, 78.2, 88.2, 98.2, and 98.2). Milk production (3.5% FCM in 305 d) was 8295, 8659, 7563, 6849, and 6000 kg for multiparous cows in treatments 1 to 5, respectively, and 7334, 7177, 6976, 6014, and 4750 kg for primiparous cows. Primiparous cows had decreased milk protein, BW gain, DMI and gross feed efficiency as forage increased in the diet. Multiparous cows in treatment 1 had depressed milk fat and lower DMI and gross feed efficiency compared with other treatments. Body condition scores tended to be lower as forage increased in the diet with both age groups. Increased forage in the diet did not cause any adverse effects on health and reproductive performance in either age group. PMID- 1918545 TI - Plasma alpha-tocopherol profiles in sheep after oral administration of dl-alpha tocopheryl acetate and d-alpha-tocopheryl succinate. AB - The purpose of this study was to compare the bioavailability of dl-alpha tocopheryl acetate and d-alpha-tocopheryl succinate when administered to sheep in a single oral dose weekly. The sheep, five per treatment, were given a basal diet without vitamin E supplement (control) or basal diet with weekly administration of 2225 IU of dl-alpha-tocopheryl acetate, 2225 IU of d-alpha-tocopheryl succinate, or 6675 IU of d-alpha-tocopheryl succinate. Increases in plasma alpha tocopherol concentration levels over the 3-wk period of study were determined and compared. The greater availability of dl-alpha-tocopheryl acetate was indicated by the significantly higher peak plasma alpha-tocopherol concentrations and the greater area under the curve produced by administration of the acetate than the succinate esters at the same dosage. Reported data on plasma alpha-tocopherol concentrations suggest that bioavailability in sheep of d-alpha-tocopheryl succinate versus dl-alpha-tocopheryl acetate is 3:1. PMID- 1918547 TI - Derivation, calculation, and use of national animal model information. AB - New terms and definitions were developed to explain national USDA genetic evaluations computed by an animal model. An animal's PTA combines information from its own records and records of all its relatives through a weighted average of 1) average of parents' evaluations, 2) half of its yield deviation, and 3) average across progeny of twice progeny evaluation minus mate's evaluation. Yield deviation is a weighted average of a cow's lactation yields minus solutions for management group, herd-sire, and permanent environmental effects. Bulls do not have yield deviations; however, a weighted adjusted for mates' merit can provide a useful, unregressed measure of daughter performance. Reliability is the squared correlation of predicted and true transmitting ability. An animal's parents, own records, and progeny each contribute amounts of information measured in daughter equivalents. Reliability of USDA evaluations then is computed as (total daughter equivalents)/(total daughter equivalents + 14). PMID- 1918546 TI - Estimation of milk protein gene frequencies in crossbred cattle by maximum likelihood. AB - A maximum likelihood method is presented to estimate the fraction of animals misclassified and breed effects for milk protein gene frequencies based on crossbred data. A simulation study indicates that the method provides estimates of gene frequencies that agree closely with the true values. Gene frequencies in the Dutch Black and White and the Dutch Red and White crossbred populations, based on data on 10,151 and 580 animals respectively, were estimated. Dutch Friesian and Holstein-Friesian breeds differ in gene frequencies for beta-casein and beta-lactoglobulin. Estimates for fractions misclassified are zero for alpha s1-casein, .09 for beta-casein and beta-lactoglobulin, and .12 for kappa-casein. Differences between Dutch Red and Whites and Red Holstein-Friesian breeds are small, and estimates for fractions misclassified are high but have high approximate standard errors. Compared with the Black and White breeds, the Red and Whites have a high kappa-casein B gene frequency. PMID- 1918548 TI - Selection of bulls for progeny testing using pedigree indices and characteristics of potential bull-dams' herds. AB - A total of 209 bulls selected from herds in the northeastern US by Eastern AI Coop., Inc. from 1978 to 1981 were identified. The DHI data were obtained for the 145 herds from which these bulls were sampled. Also acquired were evaluations from both Modified Contemporary Comparison and animal model on these bulls and their ancestors and on cows and their sires in the bull-dam herds. From evaluation by animal model, animals appeared to have contributed information to each other effectively through relationship matrix, and thus the accuracy of cow evaluation has been improved. Bulls selected from herds of high genetic level were genetically superior to those from herds of low genetic level. However, there was no evidence that bulls from low intraherd milk variation herds were superior to those from high variation herds in the northeastern population, as was the case in Michigan herds. Parent indices were greater than bull PTA in herds of lower genetic level but less than bull PTA in herds of higher genetic level. The correlation between herd yield average and herd genetic level and that between herd yield average and intraherd yield SD were moderate but significantly different from zero. Other correlations between phenotypic and genetic measures of bull-dam herds were negligible. None of the herd characteristics showed promise in characterizing herds that were more successful in having their sampled bulls returned by AI organization after progency test. PMID- 1918549 TI - Fundamentals of cell proliferation: control of the cell cycle. AB - Cell proliferation in higher eukaryotes is controlled by the extracellular environment and the state of differentiation. Many cells exist in a nondividing growth state termed quiescence. Some quiescent cells cannot proliferate and are said to be terminally differentiated. Others can be stimulated to divide in response to environmental signals or when cell replacement is needed. Finally, some cells undergo continual proliferation and differentiation. Growth regulatory factors generally act at specific stages of the cell cycle, most commonly during the first gap phase of the cell cycle. Once cells initiate DNA synthesis, they are generally committed to complete DNA replication. After DNA synthesis, additional signals determine whether cells in the last gap phase proceed through mitosis. In recent years, genes that appear to be critical for progression through the first two gap phases have been identified. Many are proto-oncogenes and therefore can neoplastically transform certain cells when mutated or inappropriately expressed. Growth factors that stimulate proliferation induce the expression of several proto-oncogenes; growth inhibitory factors often suppress proto-oncogene expression. As cells differentiate, the response to extracellular factors changes. In many cases, this may be due to intracellular controls that alter the response of certain proto-oncogenes to external signals. PMID- 1918550 TI - Control of growth and differentiation of the mammary gland by growth factors. AB - Mammary gland development is a complex process regulated by various steroid and polypeptide hormones. Although the systemic importance of hormones, such as estrogen, progesterone, prolactin, and growth hormone, in the growth of the mammary gland has been well documented, these hormones are virtually incapable of stimulating mammary cell growth in vitro. Thus, the growth stimuli for mammary cells requires clarification. In recent years, a number of growth factors have been discovered; this has prompted interest in examining possible involvement of these biologically active agents in the process of mammary gland development. Results presented herein indicate that several growth factors including epidermal growth factor, transforming growth factor alpha and beta, basic fibroblast growth factor, insulin-like growth factor-I, and mesenchyme-derived growth factor participate in the regulation of mammary cell growth and differentiation. PMID- 1918551 TI - Replications of a dual failure model for boys' depressed mood. AB - A structural equation model for depressed mood was examined for three samples of boys (N = 317) from at-risk families. It was assumed that rejection by normal peers and academic failure were significant covariates for preadolescent boys' depressed mood. The model accounted for from 51% to 68% of the variance in the criterion construct. The confirmatory factor analyses showed an adequate fit of the measurement model to the data sets for each of the three samples. The hypothesized negative path coefficients from the good peer relations construct to the child depressed mood construct were significant for all three samples. The path from the academic skills construct to the child depressed mood construct, however, was highly variable and significant for only two of the samples. Multigroup comparisons were carried out to determine the degree to which the factor loadings and the structural relations between constructs were invariant across the three samples. PMID- 1918552 TI - Structure of problem behaviors in preadolescence. AB - Earlier research suggests that diverse adolescent problem behaviors, such as substance use, school problems, early sexual intercourse, and delinquency, reflect a single underlying dimension of behavior. Data from an ongoing longitudinal study were used to examine this issue in a previously unexamined sample (N = 426) of preadolescent sixth-grade youth. Ss included boys and girls from diverse socioeconomic and racial/ethnic backgrounds, whose average ages were 11 and 12. By using confirmatory factor analyses to test competing models, multiple factor structures were detected, suggesting that earlier findings supporting a single factor conceptualization may not be generalizable to this age group. Implications of the finding that problem behaviors may be more differentiated in late childhood than in adolescence are discussed. PMID- 1918553 TI - The role of home practice in thermal biofeedback. AB - The role of regular home practice of hand warming was examined in the thermal biofeedback (TBF) treatment of vascular (migraine and mixed migraine and tension) headache (HA) by giving 12 sessions (over 6 weeks) of TBF to two groups of vascular HA patients (n = 23 per group). One group was asked to practice regularly at home with a home trainer between clinic sessions, whereas no mention of practice was made to the other group. A third group merely monitored HAs. Treatment was superior to no treatment. There was no advantage for the group receiving home practice, either in headache reduction or in acquisition of the hand-warming response. PMID- 1918554 TI - Learning and memory function in men with untreated blood pressure elevation. AB - Learning and memory processes were compared in 20 men with untreated blood pressure elevation and 20 normotensive control subjects matched for age, education, and average alcohol consumption. Subjects were identified from a larger sample of 469 factory workers who had participated in an epidemiologic investigation. Three measures (e.g., Symbol-Digit Learning Test [Ryan & Butters, 1980] and Visual Reproductions-Immediate and Delayed Recall [Wechsler, 1945] ) from a previously administered test battery were chosen for comparison on the basis of statistical power calculations. Results indicate that relative to normotensive control subjects, men with elevated blood pressure performed more poorly on all three tests. These results are independent of other known influences on neuropsychological performance and are likely a consequence of elevated blood pressure. PMID- 1918555 TI - Preparing patients for cancer chemotherapy: effect of coping preparation and relaxation interventions. AB - Sixty cancer chemotherapy patients were randomly assigned to one of four treatments: (a) relaxation training with guided relaxation imagery (RT), (b) general coping preparation package (PREP), (c) both RT and PREP, or (d) routine clinic treatment only. All patients were assessed on self-report, nurse observation, family observation, and physiological measures and were followed for five sequential chemotherapy treatments. Results indicate that the PREP intervention increased patients' knowledge of the disease and its treatment, reduced anticipatory side effects, reduced negative affect, and improved general coping. RT patients showed some decrease in negative affect and vomiting, but not as great as in past studies. The data suggest that a relatively simple, one session coping preparation intervention can reduce many different types of distress associated with cancer chemotherapy and may be more effective than often used behavioral relaxation procedures. PMID- 1918556 TI - Effects of commitment to abstinence, positive moods, stress, and coping on relapse to cocaine use. AB - In a prospective study of 104 cocaine patients, a baseline assessment was conducted while Ss were in treatment. After treatment completion, Ss were assessed once a week for 12 weeks, then 6 months from study start. A goal of absolute abstinence, greater expected success in quitting, and positive moods predicted a lower risk of a lapse in the first 12 weeks of follow-up. Stress (negative moods, physical symptoms, hassles, and life events) did not predict. Use of more coping strategies predicted abstinence for Caucasian but not for African-American Ss. Baseline measures of expected success and desire to quit predicted continuous abstinence at 6 months but not at statistically significant levels. Results suggest that solidifying abstinence goals and enhancing positive moods may facilitate early abstinence. PMID- 1918557 TI - Community mental health services for ethnic minority groups: a test of the cultural responsiveness hypothesis. AB - This study investigated services received, length of treatment, and outcomes of thousands of Asian-American, African-American, Mexican-American, and White clients using outpatient services in the Los Angeles County mental health system. It tested the hypothesis that therapist-client matches in ethnicity and language are beneficial to clients. Results indicate that Asian Americans and Mexican Americans underutilized, whereas African Americans overutilized, services. African Americans also exhibited less positive treatment outcomes. Furthermore, ethnic match was related to length of treatment for all groups. It was associated with treatment outcomes for Mexican Americans. Among clients who did not speak English as a primary language, ethnic and language match was a predictor of length and outcome of treatment. Thus, the cultural responsiveness hypothesis was partially supported. PMID- 1918558 TI - Depression in the community: an investigation into age of onset. AB - Age of onset of any lifetime depressive disorder was investigated to identify periods of the life course associated with increased risk of depression. In this large community-based sample of adults, one fourth of those with a major depressive disorder at some point in their lives reported onset during childhood or adolescence; over one half reported onset by age 25. Women were likely to have an earlier onset of depression than were men; non-Hispanic Whites and Mexican Americans born in the United States reported earlier onset than did Mexican American immigrants. Age of onset did not appear to be consequential in terms of the number, type, or severity of the symptoms occurring during the worst depressive episode or with the probability of relapse. These findings imply that age of onset may contribute to group differences in prevalence rates. PMID- 1918559 TI - Marital therapy as a treatment for depression. AB - The purpose of this study was to compare cognitive-behavioral therapy (CT; n = 20), behavioral marital therapy (BMT; n = 19), and a treatment combining BMT and CT (CO; n = 21) in the alleviation of wives' depression and the enhancement of marital satisfaction. BMT was less effective than CT for depression in maritally nondistressed couples, whereas for maritally distressed couples the two treatments were equally effective. BMT was the only treatment to have a significant positive impact on relationship satisfaction in distressed couples, whereas CO was the only treatment to enhance the marital satisfaction of nondistressed couples. On marital interaction measures CO was the only treatment to significantly reduce both husband and wife aversive behavior and to significantly increase wife facilitative behavior. PMID- 1918560 TI - Marijuana and cocaine effect expectancies and drug use patterns. AB - Self-reports from 704 college students were content analyzed and used to develop the Marijuana Effect Expectancy Questionnaire and Cocaine Effect Expectancy Questionnaire. Responses were examined using exploratory and confirmatory principle components analysis. Six marijuana expectancies (34.6% of variance) were identified: (a) cognitive and behavioral impairment, (b) relaxation and tension reduction, (c) social and sexual facilitation, (d) perceptual and cognitive enhancement, (e) global negative effects, and (f) craving and physical effects. Five cocaine expectancies (32.5% of variance) consisted of (a) global positive effects, (b) global negative effects, (c) generalized arousal, (d) anxiety, and (e) relaxation and tension reduction. Drug effect expectancies distinguished between patterns of nonuse and varying degrees of use of these two drugs. PMID- 1918562 TI - Applying statistical control theory to bring together clinical supervision and psychotherapy research. AB - A three-factor experiment was designed to evaluate the potential for improving first-session performance of 6 trainee-therapists as measured by postsession client ratings (N = 48). Rather than through standardizing therapist behavior by using a training manual beforehand, therapist effects were handled through statistical control. This method not only provided control so that findings were not confounded with some kinds of therapist effect but also identified which therapists needed supervision to bring their performance more in line with others in the group. Reducing the number of therapists requiring "standardization" should lower training costs and enhance individual freedom. In the present study, more frequent empathic responses led to statistically significant beneficial effects on five of seven outcome measures. Suggestions volunteered by therapists improved overall session ratings on three variables and increased scores on a measure of passive dependence. Whether or not therapists asked questions had no main effects on any tested outcome measure. PMID- 1918561 TI - Onset of depression and time to treatment entry: roles of life stress. AB - Patients with depression vary greatly in the time between onset of disorder and entry into treatment. Few data exist on the dimensions of this time interval and the forces that influence it. The present article outlines considerations for research on this topic and presents findings for outpatient depressives (N = 61) on life stress and the time lag between onset and treatment entry. Results indicate that life stress occurring before the onset of depression is highly predictive of time to treatment entry. In marked contrast, stress occurring after onset is not associated with this time interval. Further analyses suggest different mechanisms of association between different stress variables and time to treatment entry. The clinical implications for alleviating suffering from a depressive episode and for decreasing the likelihood that depression will lead to disruption in other spheres of the person's life are discussed. Overall, the results add to the emerging literature on life stress and depression, enlarging the scope to include forces operative in seeking formal treatment. PMID- 1918563 TI - Factors predicting attendance at self-help groups after substance abuse treatment: preliminary findings. AB - Some researchers and clinicians believe that only a fairly homogeneous subset of substance abusers are likely to affiliate with self-help groups, whereas others argue that self-help groups appeal to a wide range of persons and that selective referral of clients to self-help may be premature. This study followed 201 treated substance abusers for 6 months and found that contrary to prevailing opinion, Blacks and women were more likely to attend self-help groups and the measures of social stability did not predict attendance. In accord with other investigations, this study found that persons who attended the groups had more severe problems in several domains. Implications for clinical referral policies are discussed. PMID- 1918564 TI - Relation between differential emotions and depression in emotionally disturbed children and adolescents. AB - Differential emotions theory (Izard, 1972) provides a conceptual framework for the role of emotions in affective disorders. The present study investigated the relation of emotions to depression in a sample of child and adolescent psychiatric inpatients (N = 145). Findings indicate that shyness, anger, enjoyment, and shame explained 51.4% of the variance in depression scores. Furthermore, profiles of emotions experienced by youths with a depressive disorder differed significantly from emotion profiles of nondepressed youths on the following emotions: enjoyment, surprise, sadness, anger, shame, shyness, guilt, and self-directed hostility. Differential emotions also correctly classified 80.0% of depressed and nondepressed subjects into their respective groups. PMID- 1918565 TI - Messages of medication: effects of actual versus informed medication status on hyperactive boys' expectancies and self-evaluations. AB - After 15 boys with attention-deficit hyperactivity disorder (ADHD) were informed that they had taken either medication or placebo, they completed computer tasks, self-assessments, and causal judgments. The boys predicted better performance when told they were on medication versus placebo. For self-evaluations, medication status and information interacted, with boys actually taking placebo rating themselves more positively when told they had taken medication versus placebo. These effects were more apparent following failure than success. Both ADHD and comparison boys overestimated future classroom performance, with the former more unrealistic. Discussion focused on difficulties in assessing children's causal reasoning and the need to monitor emanative effects of pharmacotherapy on self-cognitions. PMID- 1918566 TI - [Deep bite correction in adult patients]. AB - Excessive occlusal force caused by deep bite is an etiology of alveolar bone resorption as well as premature loss of permanent teeth. Deep bite correction in adult patients should comprise of intrusion and/or proclination of anterior teeth in order to prevent skeletal alteration and relapse. The objective of the article was to present indication and mechanics of intrusion and proclination of anterior teeth with a case report of the patient who had a problem of masticatory system especially temporomandibular joint, cuspid protection system and deep bite. PMID- 1918567 TI - [Calculus accumulation on tooth surface in children]. AB - The project was designed to study the accumulation of calculus on the tooth surface in school children. One hundred and twenty two 10-15 years of age school children in both sexes were participated in the study. They were evaluated by a dentist for the presence and quantity of calculus deposits on the labial and lingual surfaces of the lower six anterior teeth using Volpe-Manhold calculus scoring method. The subjects were divided into three groups according to their calculus scores as "slight" (10-25 mm.) "moderate" (26-40 mm.) and "heavy" (greater than 40 mm.). Then all subjects received a complete oral prophylaxis, including the removal of all subgingival and supragingival deposits. At six months and twelve months after oral prophylaxis all subjects were evaluated for the calculus deposition by the same dentist. The results revealed that redeposit of calculus at six and twelve months of the three groups were statistically different (p less than 0.05). The "slight" calculus group had the calculus deposit, after oral prophylaxis, less than the "moderate" and the "heavy" group. The "heavy" group had the calculus deposit much more than the "moderate" group. PMID- 1918568 TI - [Quality assessment of amalgam restorations provided for primary school children]. AB - This study was based on the examination of 726 amalgam restorations of the permanent molar teeth, 331 teeth from boys and 395 teeth from girls. The age distribution of amalgam restorations was 6-30 months, and the age of children was 6-12 years when teeth to be filled. The purpose of the study was to assess the prevalence of recurrent caries of teeth restored and quality of amalgam restorations rendered by dentists. The results showed that the age of majority of children whose teeth restored was 9 years old, 28.7 percent of all. 91.1 percent of the restorations were one surface fillings, 68.30 and 22.8 percent were occlusal and other single surface respectively. The recurrent caries found in both fracture and sound fillings were 19.42 percent. The rate of fracture was 48.10 percent and increased with the increasing age of restorations. At 19-24 months the fracture rate was highest, 54.1 percent. The defect of surface was 51.52 percent, that did not increase with the increase of restoration age. A statistically significant correlation was found between the defect of surface texture and fracture of restoration. PMID- 1918569 TI - [Comparison of some subgingival microflora from juvenile periodontitis before and after scaling and root planing]. AB - Actinobacillus actinomycetemcomitans and Capnocytophaga are subgingival bacteria that have correlation with juvenile periodontitis. Studies were carried out in a group of 20 patients with juvenile periodontitis before, after treatment by scaling, root planing, oral hygiene instruction and 20 patients with healthy gingiva as a control group. Gingival index, plaque index, pocket depth were measured. Subgingival bacteria were counted on selective media and compared by phase contrast microscopy. Before treatment all measurements in the patients and the control group were significantly different (P less than 0.05). In the patients before and after treatment all clinical measurements were significantly different (P less than 0.05) but the amount of A.actinomycetemcomitans and Capnocytophaga were not significantly different (P greater than 0.05). These results indicate that treatment of juvenile periodontitis by scaling, root planing and oral hygiene instruction improve the clinical measurements but are not effective in reducing proportions of subgingival bacteria. PMID- 1918570 TI - [Scleroderma]. AB - Scleroderma is a systemic disease that not only causes pathology in several organs but also has interesting oral manifestations. The patients could come to see dentist due to abnormalities in oral cavity or complications from the progression of the disease. The purpose of this article is to update information about scleroderma in order to assist dentist in diagnostic process and dental treatment. PMID- 1918571 TI - [Preventive dentistry for children. 2. Plaque control, diet modification, and infant oral health counseling]. AB - Although systemic and topical fluoride together with sealant can be used to prevent dental caries efficiently. There are three more procedures of preventive dentistry in children which dentists should educate parents and children along with the first two routinely. The reasons, problems and techniques of dental health education in plaque control, diet and infant oral health counseling will be reviewed in this article. PMID- 1918572 TI - Effects of salivary film velocity on pH changes in an artificial plaque containing Streptococcus oralis, after exposure to sucrose. AB - Results from a computer model suggest that following exposure of dental plaque to sucrose, the rate of clearance of acids from plaque into the overlying salivary film will be greatly retarded at low film velocities. This was investigated with an in vitro technique in which artificial plaque containing S. oralis cells was exposed to 10% sucrose for one min. The pH at the proximal (P) and distal (D) undersurfaces of the plaque (0.5 or 1.5 mm thick) was then monitored during the passage of a 0.1-mm-thick film of a sucrose-free solution over the surface. Over the range of salivary film velocities that have been estimated to occur in vivo (0.8-8 mm/min), lower minimum pH values and increased times for the pH to recover toward neutrality occurred at the lower salivary film velocity. Lower pH values were also reached with the 0.5- than with the 1.5-mm-thick plaque. P/D pH gradients, with a lower pH distally, developed at film velocities of 0.8 and 8 mm/min, and the gradients were much more pronounced at the lower velocity. No P/D pH gradients developed when the film velocity was 86.2 mm/min. Incorporation of dead S. oralis cells into the plaque at percentages up to 57% reduced the extent of the pH fall and prolonged the recovery of the pH toward neutrality. The results support the prediction that, other factors being equal, plaque located in regions of the mouth with low salivary film velocity will achieve pH values lower than those of plaque of identical dimensions and microbial composition located in areas where salivary film velocity is high. PMID- 1918573 TI - Effects of salivary bicarbonate content and film velocity on pH changes in an artificial plaque containing Streptococcus oralis, after exposure to sucrose. AB - Chewing-gum stimulation of salivary flow (at the time of the pH minimum following exposure of plaque to carbohydrate) has been shown to cause a rapid increase in plaque pH. The objective of this study was to determine whether the rise in plaque pH is primarily due to the increased buffering capacity of stimulated saliva, or to the fact that an increased flow rate increases the concentration gradient for acid to diffuse from the plaque into the overlying salivary film, which will be moving at a higher velocity. This was investigated with an in vitro technique in which artificial plaque (0.5 or 1.5 mm deep) containing S. oralis cells was exposed to 10% sucrose for one min. The pH values at the proximal and distal undersurfaces of the plaque were then monitored during the passage of a 0.1-mm-thick film of a sucrose-free artificial saliva over the surface, at a range of film velocities (0.8-8 mm/min) that have been estimated to occur in vivo. When a minimum plaque pH had been achieved, the salivary film velocity was either (a) kept the same, with or without 15 mmol/L HCO3 (the concentration measured in chewing-gum-stimulated saliva), (b) increased to 86.2 mm/min, or (c) increased to 86.2 mm/min with 15 mmol/L HCO3 added to the artificial saliva. The findings suggest that after sucrose ingestion, the rapid rise from minimum plaque pH values, which can occur with gum-chewing stimulation of salivary flow, is due to the combined effects of the increase in salivary film velocity, and of a greater availability of bicarbonate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918575 TI - Masseter muscle thickness measured by ultrasonography and its relation to facial morphology. AB - The aims of this study were to evaluate ultrasonography as a method for measuring masseter muscle thickness, to quantitate the normal range of the ultrasonically measured thickness of the masseter in adults, and to test whether the variation in the thickness of the muscle is related to the variation in the facial morphology in different individuals. In 40 healthy, fully-dentate young adults, 20 men and 20 women, the masseter thickness was measured bilaterally by a real time ultrasound imaging technique. The measurements were performed under both relaxed conditions and with maximal clenching. Standardized facial photos of the subjects were taken so that their facial morphology could be determined. The measurement error of the thickness of the masseter was found to be small, not exceeding 0.49 mm. Under relaxed conditions, the mean thickness (+/- S.D.) of the muscle in men was 9.7 (+/- 1.5) mm, and under contracted conditions, 15.1 (+/- 1.9) mm. In women, the respective measurements were 8.7 (+/- 1.6) mm and 13.0 (+/ 1.8) mm. The thickness of the masseter muscle was found to be related to the facial morphology, mainly in women, but not in men; the women with a thin masseter had a proportionally longer face. Ultrasonography was found to be a reliable and accurate method for study of the thickness of the masseter muscle. There was a large variation in the thickness of the muscle between individuals, and the thickness of the masseter was related to facial morphology in women. PMID- 1918574 TI - Classification tree prediction models for dental caries from clinical, microbiological, and interview data. AB - Caries prediction by Classification And Regression Tree (CART) analysis is an appropriate and powerful alternative or complement to the commonly used classification methods of logistic regression and discriminant analysis, both parametric and nonparametric. The binary classification tree method discussed in this article is designed for complex data and does not require assumptions about the predictor variables or about the presence or absence of interactions among the predictor variables. Furthermore, the results give insight into the structures and interactions in the data and are easy to interpret and apply. In preliminary applications of the CART algorithms to data from The University of North Carolina Caries Risk Assessment Study, the method produced prediction rules having sensitivities and specificities that were similar to or slightly better than those associated with logistic and discriminant analyses. The classification trees constructed tended to involve far fewer predictor variables than required for adequate logistic and discriminant models. For example, for first-grade children in Aiken, South Carolina, nine variables were used to define a prediction rule having 64% sensitivity and 86% specificity. Ten-fold cross validation estimates for future data were 58% and 79%, respectively. For first grade children in Portland, Maine, two variables were used to define a prediction rule having 62% sensitivity and 77% specificity. The cross-validation estimates for future data were 58% and 78%, respectively. A brief, and previously unavailable, explanation of the CART method is given for the special case of a dichotomous outcome variable. PMID- 1918576 TI - Serum fluoride level and fluoride content of enameloid. AB - We investigated diverse groups of fish species to determine whether the fluorine (F) contents of the dental hard tissues were related to baseline serum F levels. Serum samples, enameloid, dentin, ganoid/enamel, and bone were analyzed for F by either electron microprobe or wet chemistry. Species were categorized into two groups based on the F content of the enameloid. One group contained greater than 2.6 wt% F in enameloid, whereas the other group had less than 0.45 wt% F in enameloid. The dentin and bone from all species (or, in skates, the cartilage), as well as the ganoid/enamel layer of a Holostean fish (alligator gar), showed consistently low F content. In those species whose teeth developed in sequential rows, the F content of enameloid increased with progressive tooth development. The serum F levels of all fish were below 0.05 microgram F/mL (2.63 mumol/L) and were not significantly related to the F content of the enameloid. The results substantiate the idea that F incorporation into enameloid is related to fish phylogeny, not food or habitat. It is suggested that specialized outer dental epithelial cell configurations may facilitate the incorporation of F into enameloid. PMID- 1918578 TI - Influence of operatory size and nitrous oxide concentration upon scavenger effectiveness. AB - Concern regarding environmental health hazards for dental personnel chronically exposed to waste nitrous oxide (N2O) prompted this investigation. The influence on ambient N2O levels of scavenging, operatory size, and N2O concentration delivered to the patient was evaluated during treatment of 36 pediatric dental patients. The results showed that scavenging significantly reduced ambient N2O levels measured at 50-56 cm from the patient's nose. Scavenged ambient N2O levels were also observed to decrease when N2O concentrations administered to the patient were reduced from 50 to 30%. This concentration effect was not observed in the non-scavenged groups. ANOVA showed that operatory size exerted a non significant influence on ambient N2O. The data collected during routine treatment of pediatric dental patients demonstrated that the scavenging system tested significantly reduced waste N2O in the operator's breathing zone, nearly approximating the 25-ppm recommendation established by the National Institute for Occupational Safety and Health (NIOSH). PMID- 1918577 TI - The effect of thromboxane on contraction of canine mesenteric and lingual arteries. AB - Thromboxane A2 (TXA2), a potent vasoconstrictor agent, is released from platelets and smooth muscle during inflammation and trauma. TXA2 may cause lingual artery (LA) contraction, leading to lingual paresthesia. The effects of U-46619, a TxA2 mimetic, on isolated rings of canine LA and mesenteric artery (MA) were examined. U-46619 (1 nmol/L to 1 mumol/L) caused a triphasic contraction of LA and MA; a rapid, phasic contraction; a slow, sustained contraction; and, upon washout of U 46619, a maintained contraction. The MA relaxed slowly, but the LA remained contracted for at least three h after washout. Decreasing extracellular calcium ion (Ca2+o) to less than 0.1 mumol/L with 2 mmol/L EGTA relaxed MA, but not LA. EGTA (4 mmol/L) partially relaxed the maintained contraction of LA. Inhibition of protein kinase C with amphotericin B or staurosporine inhibited the phasic and sustained contractions of LA, but did not affect the maintained contraction in the presence or absence of EGTA. Thus, CA2+o was required for the initial contraction of the LA by U-46619, but did not appear to be required for the maintained contraction following washout of U-46619. The data support the conclusion that following a brief exposure to U-46619, maintained contraction of LA persists by a unique mechanism that may be independent of Ca2+ and protein kinase C. Sustained LA contraction after exposure to endogenous TXA2 during inflammation and trauma may contribute to impaired lingual blood flow and orofacial tissue injury. PMID- 1918579 TI - Bonding efficacy of erythritol methacrylate solutions as dentin primers. AB - The bonding efficacy of aqueous solutions of two kinds of erythritol methacrylates as dentin primers was examined by measurement of the polymerization contraction gap of a light-activated resin composite in a cylindrical dentin cavity and the tensile bond strength of the composite to the flat dentin surface. The dentin surface was cleaned with neutralized 0.5 mol/L EDTA and pre-treated with a meso-erythritol or penta-erythritol methacrylate solution, followed by application of a commercial dentin bonding agent (Clearfil New Bond) and a resin composite. Among the tested primers, a 40% meso-erythritol methacrylate solution was shown to be the most effective because, in contrast to the other primers, contraction gap formation by the composite was prevented in all tested specimens. PMID- 1918580 TI - The surface roughness of enamel-to-enamel contact areas compared with the intrinsic roughness of dental resin composites. AB - The purpose of this study was to determine the surface roughness of enamel-to enamel contact areas in order to provide a standard for comparison with surface characteristics of commercially available composite restorative materials. In addition, the inherent surface roughness of resin composites was evaluated profilometrically after a toothbrush abrasion procedure. A one-sided t-test analysis was performed to outline significant differences between the surface roughness value of enamel facets and that of the respective composite samples. A surface roughness of 0.64 +/- 0.25 micron (mean +/- S.D.) was found for the enamel-to-enamel contact areas. PMID- 1918581 TI - Effect of a beta-adrenergic blocking agent on dental anxiety. AB - The effect of propranolol was studied on 23 dental phobics in a double-blind, placebo-controlled clinical trial involving actual dental treatment. The subjects were selected because they showed high physiological reactivity in the dental situation. Twelve subjects received the test drug and 11 subjects received the placebo at individualized doses of either 80 or 120 mg. A significant difference in self-reported anxiety at the injection phase of treatment and less overall pain intensity and aversiveness were observed for the propranolol as compared with the placebo group. No differences were detected for behavior ratings. Beta adrenergic blocking agents may have utility for reducing anxiety in individuals fearful of dental treatment. PMID- 1918582 TI - The dental diagnostic sciences and the future of dental practice. PMID- 1918583 TI - Squamous cell carcinoma presenting as subcutaneous nodules. AB - Four patients with squamous cell carcinomas (SCCs) presenting as subcutaneous nodules of the head were referred for Mohs micrographic surgery. In each case initial histologic sections showed no connection between the tumor and epidermis, raising the possibility that each was a metastasis from an occult SCC. Careful searches for occult SCCs were unrevealing. Subsequent step sections through the entire tumors revealed narrow connections to the overlying epidermis in three of the four cases. PMID- 1918584 TI - Squamous cell carcinoma arising in a site of chronic osteomyelitis. Treatment with Mohs micrographic surgery. AB - Squamous cell carcinoma (SCC) arising in a focus of chronic osteomyelitis is a rare but potentially fatal disease. Because of the possibility of metastases, amputation proximal to the site of the tumor is the current standard of therapy. We report the first case of SCC arising in chronic osteomyelitis treated by Mohs micrographic surgery as an alternative method of treatment. PMID- 1918585 TI - Malignant schwannoma treated by Mohs surgical excision. AB - A 34-year-old white female with a 5-cm malignant schwannoma of the upper thigh underwent complete removal of the tumor by fresh-tissue Mohs surgical excision. The patient refused postoperative radiotherapy, and is without signs of recurrence 5 years after surgery. Mohs surgical excision in the treatment of malignant schwannoma has not to our knowledge been reported previously. PMID- 1918586 TI - Compression therapy of the legs. A review. AB - Compression therapy is a powerful method for the treatment of all sorts of swollen extremities. Its effects depend on several factors, including: underlying disease, exerted pressure and body position, and compression material. PMID- 1918587 TI - Venous hypertensive microangiopathy in relation to clinical severity and effect of elastic compression. AB - Arterial inflow in mL/minute and perimalleolar skin blood flow were measured with venous occlusion air-plethysmography and laser-Doppler flowmetry in 20 normal limbs, 40 limbs with uncomplicated primary varicose veins, 32 limbs with primary varicose veins and skin changes, and 36 limbs with deep venous disease. Limbs with complicated varicose veins (skin changes) and deep venous disease showed a marked increase (2 to 4 times) in both arterial inflow and skin blood flow when compared with the normal controls and uncomplicated varicose veins. The measurements were repeated 30 minutes after the application of graduated elastic stockings. There was a 16% reduction in the mean arterial inflow (P less than .01) and a 45% decrease in skin blood flow (P less than .01). The results indicate that in limbs with chronic venous insufficiency and skin changes there is an increased blood flow which is mainly in the skin. This is irrespective of whether the venous problem is in the superficial or deep venous system. Elastic compression tends to reduce the hyperemia towards the normal range. PMID- 1918588 TI - Muller phlebectomy. A new phlebectomy hook. AB - The phlebectomy hooks allow aesthetic and efficient removal of all types of varicose veins by means of small incisions (1-3 mm) according to the technique invented by Dr. Robert Muller. Brief review of Muller's phlebectomy and discussion of the advantages of this new device. PMID- 1918589 TI - The out-patient therapy of trunk varicosis of the greater saphenous vein by means of ligation and sclerotherapy. A contribution from a German phlebology practice. PMID- 1918590 TI - Squamous cell carcinoma arising in hidradenitis suppurativa. AB - The case reported concerns a 57-year-old man with a 35-year history of hidradenitis suppurativa lesions confined to his buttocks and recently complicated by a large, ulcerated, well-differentiated squamous cell carcinoma. Wide surgical excision and grafting, requiring temporary colostomy, were performed with no recurrence or metastasis during the following 12 months. The relevant literature is reviewed and discussed. PMID- 1918591 TI - An improved design for vermilionectomy with a mucous-membrane advancement flap. AB - The author describes a modified mucous-membrane advancement flap for the repair of defects following the removal of premalignant actinic cheilitis or squamous cell carcinoma. The advantages of this modification over other techniques include a more broadly resurfaced lip bilaterally, and prevention of punctate scarring at the lateral oral commissures by use of a continuous mucous membrane in and around the commissures themselves. PMID- 1918592 TI - Functional analysis of HLA-DR-expressing keratinocytes from tuberculin reactive skin. AB - We examined the functional roles of HLA-DR+ keratinocytes which were induced in vivo from tuberculin reactive skin. At 4 days after intradermal PPD injection, about 80% of keratinocytes obtained from the tuberculin reactive area expressed DR antigens. In 14 of 18 individuals examined, PPD-pulsed DR+ keratinocyte fraction induced autologous T-cell proliferation. The proliferative response was PPD-dependent, antigen specific; it depended upon DR expression by the keratinocyte fraction, because it did not occur in the presence of the PPD nonpulsed DR+ keratinocyte fraction and was completely blocked by mouse monoclonal antibody to HLA-DR. However, the antigen-presenting capacity of the DR+ keratinocyte fraction appeared to be less than that of monocytes or the DR+ epidermal cell fraction. The DR+ keratinocyte fraction was also able to stimulate allogeneic T-cell DNA synthesis, but the DR- keratinocyte fraction could not. The possible influences of contaminant Langerhans cells and mononuclear cells in the DR+ keratinocyte fraction were considered to be unlikely. These results suggest that DR+ keratinocytes, which are induced in vivo, can both present the antigen to autologous T cells and stimulate allogeneic T cells. PMID- 1918593 TI - Topical psoralen photochemotherapy for atopic dermatitis: evaluation of two therapeutic regimens for inpatients and outpatients. AB - Forty-seven adolescent and adult patients suffering from long-standing atopic dermatitis (AD) too severe to respond to conventional therapies were treated with topical psoralen photochemotherapy (PUVA) and relatively low doses of ultraviolet (UV) irradiation. For practicality and convenience, two different therapeutic regimens were implemented; short-term hospitalization with almost daily irradiation (inpatient group, n = 23) and weekly irradiation combined with topical corticosteroids which had failed to manage symptoms before initiating the treatment (outpatient group, n = 25). Excellent therapeutic effects were achieved in 72% of the inpatients after 5-38 (mean 18.2) times of irradiation (mean cumulative dose; 44.7 J/cm2). In addition, 56% of outpatients responded excellently to the treatment after 6-22 (mean 13.0) times (mean cumulative dose; 25.8 J/cm2). In fact, 16 of the inpatients and 10 of the outpatients achieved almost complete remission. The duration of remission in these patients was 1-25 months (mean 6.3 months) in the inpatients and 1-6 months (mean 3.0 months) in the outpatients. Peripheral blood eosinophils significantly decreased after the treatments. A follow-up study showed a delayed decrease in serum IgE levels. In contrast, the specific IgE to house dust antigens and the water holding capacity of stratum corneum did not vary after treatment. PMID- 1918594 TI - A case of seminal fluid allergy successfully treated with immunotherapy in a one day rush procedure. AB - A 28-year-old woman was treated for seminal fluid allergy with immunotherapy using a one-day 'rush' procedure. Apart from minor anaphylactic symptoms, no serious side effects were noted during or after hyposensitization or boostering. Five weeks after the start of the hyposensitization, she was free of symptoms after unprotected coitus. PMID- 1918595 TI - Heterogeneity of clinical features of pseudoxanthoma elasticum: analysis of thirteen cases in Oita Prefecture from a population of 1,240,000. AB - Thirteen cases among 16,260 patients seen at our department during the nine years from 1981 were diagnosed as pseudoxanthoma elasticum (PXE). The sex and age distributions were similar to those so far reported in the literature. There were two cases of the autosomal dominant type. One patient had skin lesions typical of PXE in association with Ehlers-Danlos syndrome. In two of three patients with cutis laxa-like lesions, eruptions of elastosis perforans serpiginosa were present. In three cases, we failed to detect deposition of calcium in typical skin lesions in either an early or a late stage by histochemical staining, in spite of the presence of slightly degenerated elastic fibers. PMID- 1918596 TI - Cutaneous metastasis of renal cell carcinoma: an electron microscopic study. AB - A case of cutaneous metastasis of renal cell carcinoma in a 67-year-old man is described. Right side nephrectomy had been performed three years earlier, and a renal cell carcinoma was diagnosed. Following a bruise, the patient noticed an erythematous nodule on the scalp. Histological examination of this skin lesion showed atypical tumor cells consisting predominantly of clear cells with a honeycomb-like or adenoid structure. Electron microscopic examination revealed that the tumor cells were divided into three groups: clear cells with abundant glycogen, dark cells with abundant mitochondria, and intermediate cells containing both glycogen and mitochondria in varying proportions. Some of the tumor cells with an adenoid pattern had a brush border-like structure in the lumen. These results support the diagnosis of metastatic renal cell carcinoma. An electron microscopic approach may aid in diagnosis of cutaneous metastasis from renal cell carcinoma. PMID- 1918598 TI - Epidermolysis bullosa acquisita in identical twins. AB - Identical twin sisters developed generalized erythema and bullae on skin and mucous membranes at 18 and 19 years of age. Atrophic scars and milia were formed later. Indirect immunofluorescence (IF) study of the separated skin by incubation in 1.0M NaCl showed antibasement membrane zone (BMZ) antibodies bound to the dermal side. The HLA-DR typing demonstrated DR2/DW11. Pulse therapy resulted in marked clinical improvement. This is the first report of epidermolysis bullosa acquisita (EBA) in identical twins and suggests the possibility that the disease may have a genetic component. PMID- 1918597 TI - Purpura fulminans secondary to Xanthomonas maltophilia sepsis in an adult with aplastic anemia. AB - Purpura fulminans is a rare disease characterized by purpura ecchymosis, hypotension, and fever associated with disseminated intravascular coagulation. It often begins as a benign infectious process and subsequently progresses to a severe, catastrophic outcome. It is recognized to originate from congenital or acquired protein C deficiency. We present an unusual case of an adult with Xanthomonas maltophilia sepsis that subsequently developed into purpura fulminans with involvement of the four extremities. We discuss the importance of the protein C system in coagulation homeostasis and its relationship to purpura fulminans. PMID- 1918599 TI - Normolipemic papuloeruptive Xanthomatosis in an infant. AB - A 8-month-old boy showed several yellow to brownish yellow, papular and/or nodular eruptions predominantly on the face. Initial clinical and histologic findings indicated possible juvenile xanthogranuloma or papular xanthoma. Since his second year, the papulonodular lesions have gradually merged into large confluent plaques, particularly on the face, nape, and axillae. Consequently, it was considered that his condition had terminated in diffuse plane xanthoma. Serum lipid panels showed normolipemia. Finally, a diagnosis of papuloeruptive xanthomatosis with normal lipid metabolism and no associated systemic disorders was made. The patient's papulonodular lesions have continued to involute spontaneously since the age of three. PMID- 1918601 TI - Diagnoses, dimensions, and DSM-IV: The science of classification. PMID- 1918600 TI - A case of cutaneous squamous cell carcinoma associated with sporadic porphyria cutanea tarda due to liver disorder after Schistosoma japonicum infection. AB - A 56-year-old man suffered from cutaneous squamous cell carcinoma (cutaneous SCC) which occurred on a cutaneous lesion of sporadic porphyria cutanea tarda (sporadic PCT). His liver function decreased from the time he was infected with Schistosoma japonicum at the age of 10. He drank a little alcohol. Erythematous maculae with blisters or erosions occurred on sun-exposed areas of his skin when he was 52. His urine continued to be red. After detailed examinations including liver biopsy, he was diagnosed as having sporadic PCT due to liver disorder after infection with Schistosoma japonicum. At the age of 56, a small red papule arose on his right earlobe at the site of a sporadic PCT lesion. The papule rapidly enlarged with ulceration; this completely destroyed his right earlobe, which was covered with odoriferous yellow-white necrotic tissue. The tumor then extended to his right preauricular area with ulceration. A skin biopsy confirmed well differentiated cutaneous SCC. The association of cutaneous SCC with sporadic PCT has not been previously reported; we think that the association is significant. Such an occurrence may have been induced by either direct or indirect effects of ultraviolet light or a scar formed by the sporadic PCT. PMID- 1918602 TI - Classification in psychopathology: rationale, alternatives, and standards. AB - The elements that constitute a scientific taxonomy are outlined and presented with reference to the structure of psychopathologic categorization and diagnosis. The terminology, logic, and conceptual issues associated with clinical classification are discussed. Alternatives for the selection of substantive clinical attributes, the overall structural format into which categories are organized, and construction procedures used in developing a psychopathologic taxonomy are elaborated, as are a number of criteria for evaluating the taxonomy's utility and efficacy. PMID- 1918603 TI - Metaphorical analysis of psychiatric classification as a psychological test. AB - In this taxonomic article we explore the metaphor of comparing a psychiatric classification to a psychological test. Structurally, diagnostic criteria are like test items; diagnostic categories are like scales; and classification are like tests. Analytically, the ideas of reliability and validity are the primary concepts invoked in the empirical evaluation of both classifications and tests. However, when the metaphor is explored in more detail, the differences between classifications and tests become clear. These differences are discussed in terms of the structural and analytical relations between tests and classifications. This metaphorical analysis of classifications as tests suggests that certain issues that have been discussed in regard to psychological tests, particularly reliability and validity, may require modification when applied to psychiatric classification. PMID- 1918604 TI - International use and attitudes toward DSM-III and DSM-III-R: growing consensus in psychiatric classification. AB - A survey of the uses and attitudes of 146 mental health professionals, primarily psychiatrists and psychologists, in 42 countries (not including the United States) toward the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) and its revision (DSM-III-R; American Psychiatric Association, 1980,1987) is reported. The results revealed wide-spread endorsement of the multiaxial system, theoretical neutrality, descriptive symptom criteria forming discrete categories, and the placement of personality disorders on a separate axis. We report that the DSM-III and DSM-III-R are more widely used around the world than the International Classification of Diseases for teaching, research, and clinical practice. Opinions about various dimensions of the DSM's usefulness and shortcomings are presented. PMID- 1918605 TI - Toward an empirical classification for the DSM-IV. AB - The provision of explicit and specific diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM; American Psychiatric Association, 1980, 1987) was instrumental in the production of a substantial amount of informative research. The major emphasis in the preparation of the DSM-IV has been to maximize the impact of this accumulating research on the revision and to document the rationale and empirical support for any changes that are made. In this article we discuss the empirical basis for the DSM-IV. The historical context provided by the previous editions is briefly presented and followed by a description of the process by which the DSM-IV is being constructed. The input of empirical data through literature reviews, data reanalyses, and field trials is described, and an illustration with the antisocial personality disorder diagnosis is given. PMID- 1918606 TI - Classification of mental disorder as a collection of hypothetical constructs. AB - In this article, I explore the implications of viewing psychiatric classification as a collection of hypothetical constructs. In this view, a taxonomic construct includes meaning surplus to the descriptive features provided by operational definitions, such as those provided in the American Psychiatric Association's 4th edition of the Diagnostic and Statistical Manual of Mental Disorders. This surplus meaning includes ties to etiology and treatment that for many disorders are as yet unknown. Despite these unknowns, it is proposed that a taxonomic construct must be embedded in a theory that provides some meaningful context for the construct and that falsification of such theories constitutes the primary enterprise of taxonomic research. PMID- 1918607 TI - An outsider-insider's views about revising the DSMs. AB - After having a leadership role in the development of the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III; American Psychiatric Association, 1980) and its revision (DSM-III-R; American Psychiatric Association, 1987), I now comment as an outsider-insider on the development of DSM-IV. Many features of the DSM-IV process, such as systematic literature reviews and focused field trials, represent significant advances that will increase the role of empirical findings in the decision-making process in this latest edition of the DSM. However, it is likely that when final decisions are made about DSM-IV, the decisions will still be based primarily on expert consensus, rather than on data, as was the case with DSM-III and DSM-III-R. PMID- 1918609 TI - Dilemmas in the pathway of the DSM-IV. AB - It is argued that the format for developing recent versions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) taxonomy is constrained in ways that seriously impair the quality of the product. These constraints include inappropriate assumption of a categorical model, ensured persistence of traditional categories of disorder, excessive concern with interdiagnostician agreement, insufficient attention to the issue of construct validity, and excessive preoccupation with clinician acceptance. These problems and certain others are illustrated with an analysis of the nosologic status of the schizophrenia construct. There is a significant danger that the adequacy of DSM IV will be compromised by continuing difficulties of this sort. PMID- 1918608 TI - Relationship between the DSM-IV and the ICD-10. AB - The 10th revision of the International Classification of Diseases and Related Health Problems (ICD-10; World Health Organization, 1990) and the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) will both come into use in 1993 and be much more alike than the ICD-9 (World Health Organization, 1978) and the DSM-III (American Psychiatric Association, 1980). The American Psychiatric Association's controversial decision to publish a revision of the DSM-III in 1987 before setting up the Task Force to produce the DSM-IV impaired the association's ability to influence the format of the ICD-10, because by then major decisions had already been made by the World Health Organization. The DSM-IV will be more soundly based on a wider range of empirical data than any previous classification, national or international, and should not be revised again without compelling scientific reasons. PMID- 1918610 TI - DSM-IV: empirical guidelines from psychometrics. AB - This commentary addresses the use of psychometric theory and methodology in the development of the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Reliability issues include interdiagnostician reliability, temporally consistent diagnoses, and the relations of diagnostic criteria within categories. Validity issues include content validity of the diagnostic criteria, criterion-related validity (the relation between different criterion sets or their algorithms and alternative diagnostic criteria), and construct validity (the relation between diagnostic categories and external validators). Specific questions and methodology to investigate its utility vary with the different uses proposed for the diagnostic system. Specific psychometric methodologies that may be useful in developing the DSM-IV are noted, as are the limitations of psychometrics and their applicability to DSM-IV. PMID- 1918611 TI - Tripartite model of anxiety and depression: psychometric evidence and taxonomic implications. AB - We review psychometric and other evidence relevant to mixed anxiety-depression. Properties of anxiety and depression measures, including the convergent and discriminant validity of self- and clinical ratings, and interrater reliability, are examined in patient and normal samples. Results suggest that anxiety and depression can be reliably and validly assessed; moreover, although these disorders share a substantial component of general affective distress, they can be differentiated on the basis of factors specific to each syndrome. We also review evidence for these specific factors, examining the influence of context and scale content on ratings, factor analytic studies, and the role of low positive affect in depression. With these data, we argue for a tripartite structure consisting of general distress, physiological hyperarousal (specific anxiety), and anhedonia (specific depression), and we propose a diagnosis of mixed anxiety-depression. PMID- 1918612 TI - Mixed anxiety and depression. AB - We review evidence from community, primary care, and psychiatric samples to determine whether there are a group of patients who have mixed symptoms of anxiety and depression that are below diagnostic thresholds for either group of disorders. A review of the data strongly suggests that such a group of patients exists and that, despite lacking sufficient symptoms to meet diagnostic thresholds from the revised 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987), they often have significant impairment in social and vocational functioning. Because many of these patients also suffer from medically unexplained somatic symptoms, they may be more likely to frequently use nonpsychiatric medical care. Longitudinal studies suggest that persons with mixed anxiety-depression symptoms may represent a population who are at increased risk for more severe mood and anxiety disorders. PMID- 1918613 TI - Diagnostic issues in posttraumatic stress disorder: considerations for the DSM IV. AB - Four issues of key interest with regard to posttraumatic stress disorder in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) are discussed. These include: (a) how to define the stressor criterion, especially, whether or not the victim's response ought to be included and whether low-magnitude traumas qualify etiologically; (b) the cohesiveness of the syndrome and the validity of items across stressor groups; (c) the position of posttraumatic stress disorder within DSM-IV; and (d) comorbidity with other illnesses. PMID- 1918614 TI - Substance use disorders in the DSM-IV. AB - Since late 1988, the Substance Use Disorders Work Group has considered alternative concepts and definitions of substance abuse and dependence and their significance for possible changes (in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders) in existing criteria for abuse and dependence. The three other matters to which the group has devoted itself include the development of guidelines for distinguishing behaviors that typically accompany the abuse of specific substances from psychiatric disorders with similar behavioral consequences, examination of the predictive validity of possible alcoholic subtypes on the basis of family history, and the relationship of the organic brain syndromes to intoxication and withdrawal. PMID- 1918615 TI - Eating disorders in the DSM-IV. AB - The guiding principles and operating procedures of the Eating Disorders Work Group are described. Provisional diagnostic criteria for the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders for anorexia nervosa and bulimia nervosa are listed, together with an explanation of how and why they differ from the revised 3rd edition (American Psychiatric Association, 1987). Consideration of a possible new diagnosis is noted. PMID- 1918616 TI - Disintegrated experience: the dissociative disorders revisited. AB - We present proposed changes to the dissociative disorders section of the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders and review the concept of pathological and nonpathological dissociation, including empirical findings on the relations between trauma and dissociative phenomenology and between dissociation and hypnosis. The most important proposals include the creation of two new diagnostic entities, brief reactive dissociative disorder and transient dissociative disturbance, and the readoption of the criterion of amnesia for a multiple personality disorder diagnosis. We conclude that further work on dissociative processes will provide an important link between clinical and experimental approaches to human cognition, emotion, and personality. PMID- 1918617 TI - Diagnostic conundrum of oppositional defiant disorder and conduct disorder. AB - Evidence for a diagnostic distinction of oppositional defiant disorder (ODD) and conduct disorder (CD) is reviewed, and alternative conceptualizations and definitions for the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders are considered. Studies suggest that CD and ODD are strongly and developmentally related but clearly different. Factor analyses indicate that distinct covarying groups of ODD and CD symptoms can be identified, but certain symptoms relate to both (particularly mild aggression and lying). Age of onset for ODD is earlier than for most CD symptoms. Nearly all youths with CD have a history of ODD, but not all ODD cases progress to CD. The disorders demonstrate the same forms of parental psychopathology and family adversity but to a greater degree for CD than for ODD. Alternative conceptualizations for the disorders are presented for further study before the introduction of the DSM-IV. PMID- 1918618 TI - Psychopathy and the DSM-IV criteria for antisocial personality disorder. AB - The Axis II Work Group of the Task Force on DSM-IV has expressed concern that antisocial personality disorder (APD) criteria are too long and cumbersome and that they focus on antisocial behaviors rather than personality traits central to traditional conceptions of psychopathy and to international criteria. We describe an alternative to the approach taken in the rev. 3rd ed. of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987), namely, the revised Psychopathy Checklist. We also discuss the multisite APD field trials designed to evaluate and compare four criteria sets: the DSM-III-R criteria, a shortened list of these criteria, the criteria for dyssocial personality disorder from the 10th ed. of the International Classification of Diseases (World Health Organization, 1990), and a 10-item criteria set for psychopathic personality disorder derived from the revised Psychopathy Checklist. PMID- 1918619 TI - Differentiation of Axis I and Axis II disorders. AB - The revised 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987) distinguishes between Axis I and Axis II disorders: Axis II includes personality (and developmental) disorders, and all others are on Axis I. This distinction is often useful, but the reification of Axis I and II constructs through diagnostic criteria sets that demarcate categorically distinct entities is at times problematic. We review the issues of differentiating personality from Axis I disorders, specifically illustrated by schizotypal and schizophrenic disorders, borderline and mood disorders, antisocial and substance use disorders, and avoidant personality from social phobia. The options for addressing their differentiation include adding exclusion criteria, shifting the placement of disorders, deleting overlapping criteria, adding differentiating criteria, and converting to a dimensional format. PMID- 1918620 TI - An A to Z guide to DSM-IV conundrums. AB - The work on the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) poses many puzzling conundrums that touch on complicated and important theoretical and practical issues. None of these can be resolved in the DSM-IV, but we hope that the Task Force's decisions will be informed by thorough reviews of the currently available evidence and extensive input from all sectors of the mental health field. In this article we provide an alphabetical guide to DSM-IV conundrums that we hope will stimulate comments, suggestions, and criticisms about the work of the Task Force. PMID- 1918621 TI - Measurements of the effective nonlinearity parameter B/A of water containing trapped cylindrical bubbles. AB - The effective nonlinearity parameter B/A of water containing a three-dimensional ensemble of randomly distributed uniform-sized trapped cylindrical bubbles was measured. The experimental results indicate that the dramatic enhancement of the effective nonlinear parameter B/A is due to the nonlinear resonance oscillation of the trapped bubbles. The measured effective B/A for the system is of the magnitude of 10(4) to 10(5). PMID- 1918622 TI - Acoustic generation of bubbles in excised canine urinary bladders. AB - A high-intensity, 555-kHz acoustic field was used to generate bubbles within urinary bladders excised from dogs. Following the exposure, bubbles were visualized on a diagnostic ultrasound scanner with a 5-MHz in-line mechanical sector scanhead. Scattering of the high-intensity ultrasound by the bubbles was also observed during the exposure as high-amplitude scan lines. The bladders used had been surgically removed after tying off the ureters and urethra to prevent urine loss and exposure to external contaminants. Each bladder was sealed in a plastic bag filled with a degassed saline solution. The bladder was centered in a sealed degassed water path at the common focus of a 7-cm-diam transducer and a 10 cm-diam brass reflector. The 555-kHz transducer and reflector were both focused at 10 cm and were aligned coaxially. Using various acoustic pressure amplitudes, two, 10-s low-frequency exposures, separated by approximately 30 s, occurred at approximately 2-min intervals. Experiments on a single bladder lasted as long as 45 min. The sizes of the largest bubbles, which were easily imaged, were estimated from rise velocity measurements as 50-70 microns in radius, and pressure amplitudes used to generate those large bubbles were estimated as 10-20 bars. The detection of smaller bubbles was limited by the inability to clearly distinguish bubble echoes from artifacts caused by the reverberant field within the bladder. Visual inspection of the exterior and interior bladder wall showed no significant discoloration within the high intensity beam path.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918623 TI - Sound exposures and hearing thresholds of symphony orchestra musicians. AB - To assess the risk of noise-induced hearing loss among musicians in the Chicago Symphony Orchestra, personal dosimeters set to the 3-dB exchange rate were used to obtain 68 noise exposure measurements during rehearsals and concerts. The musicians' Leq values ranged from 79-99 dB A-weighted sound pressure level [dB(A)], with a mean of 89.9 dB(A). Based on 15 h of on-the-job exposure per week, the corresponding 8-h daily Leq (excluding off-the-job practice and playing) ranged from 75-95 dB(A) with a mean of 85.5 dB(A). Mean hearing threshold levels (HTLs) for 59 musicians were better than those for an unscreened nonindustral noise-exposed population (NINEP), and only slightly worse than the 0.50 fractile data for the ISO 7029 (1984) screened presbycusis population. However, 52.5% of individual musicians showed notched audiograms consistent with noise-induced hearing damage. Violinists and violists showed significantly poorer thresholds at 3-6 kHz in the left ear than in the right ear, consistent with the left ear's greater exposure from their instruments. After HTLs were corrected for age and sex, HTLs were found to be significantly better for both ears of musicians playing bass, cello, harp, or piano and for the right ears of violinists and violists than for their left ears or for both ears of other musicians. For 32 musicians for whom both HTLs and Leq were obtained, HTLs at 3-6 kHz were found to be correlated with the Leq measured. PMID- 1918624 TI - Spatial response profiles of posteroventral cochlear nucleus neurons and auditory nerve fibers in unanesthetized decerebrate cats: response to pure tones. AB - Encoding of 1- and 5-kHz pure tones by auditory-nerve (AN) fibers and choppers of the posteroventral cochlear nucleus (PVCN) was investigated. Neuronal responses were analyzed as the discharge rate, rate change, and the mean and standard deviation (or sigma) of spike counts. The major findings are: (1) Sideband inhibitory areas were observed in spatial profiles of rate changes of PVCN choppers whereas they were absent in those of AN fibers; (2) spatial profiles of rate changes and mean discharge rates of PVCN choppers were sharper than those of high spontaneous-rate (HSR) AN fibers and were comparable to those of low and medium SR (LMSR) AN fibers for 1 kHz at 50 and 70 dB SPL re: 20 microPa; (3) to 5 kHz, 30 dB SPL, PVCN choppers were strongly driven comparable to HSR AN fibers whereas LMSR AN fibers were weakly driven (implying higher thresholds); (4) PVCN choppers exhibited higher maximum discharge rates (300-600 spikes/s) than either LMSR AN fibers (200-250 spikes/s) or HSR AN fibers (150-250 spikes/s); (5) mean to-sigma ratios of PVCN choppers, particularly at 70 dB SPL, were much higher than those of LMSR or HSR AN fibers; (6) rate-change profiles of LMSR AN fibers were distinct from those of HSR AN fibers, more conspicuously for 1 kHz than for 5 kHz; (7) the neural response profiles to 5 kHz were sharper than those to 1 kHz; and (8) 45% of PVCN choppers in the present study exhibited SR greater than 20 spikes/s whereas only 11%-12% of AVCN choppers in previous studies of anesthetized cats exhibited the same SR, which may represent an effect of anesthesia. The observations support a hypothesis that the transformation of the discharge-rate signal from AN fibers to PVCN choppers leads to an amplification of the mean discharge-rate signal with an increase in the signal-to-noise ratio. The observations suggest that PVCN choppers can encode pure-tone frequency in a spatial profile more accurately than HSR or LMSR AN fibers. The present data on AN and PVCN spatial profiles should be valuable to CN modeling studies by providing the input to the CN and the output of a class of physiologically characterized CN neurons for an identical set of stimuli. PMID- 1918625 TI - Electrophysiological evidence of nonlinear distortion products to two-tone stimuli. AB - Spectral analysis of auditory-evoked potential recordings from ten normal-hearing subjects to two-tone signals revealed energy at difference tone (DT = f2-f1) and cubic difference (CDT = 2f1-f2) frequencies that was not present in the acoustic signal. Control experiments and calibrations provided substantial evidence supportive of the biological nature of these auditory nonlinearities, suggesting that they are not the result of electromagnetic, acoustic, or analytic artifact. Amplitudes of DT- and CDT-evoked responses were evaluated for rarefaction and condensation signals with f1 = 510 and 800 Hz across frequency ratios (f2/f1) of 1.16, 1.26, 1.36, and 1.46. Additionally, time-domain summation and subtraction of separately collected evoked responses to rarefaction and condensation signals were performed to demonstrate that these electrophysiological DT and CDT responses reflect their expected quadratic and cubic nature. Suggestions for development of clinical applications of assessing auditory nonlinearities using this methodology are provided. PMID- 1918626 TI - Coding of vibrotactile stimulus frequency by Pacinian corpuscle afferents. AB - Psychophysical and electrophysiological techniques were used to study the encoding and processing of information about the frequency content of vibrational stimuli applied to glabrous skin in humans and cats. Trained human subjects were asked to discriminate changes in stimulus frequency and harmonic content for pairs of mono- and diharmonic sinusoidal vibrations applied to the fingertips. These psychophysical tests supplied data on what information is available to the central nervous system about the frequency components of vibratory stimuli. Electrophysiological recordings from nerves innervating the glabrous skin of the paw in cats during presentation of the same stimuli used in the psychophysical study provided data on how the peripheral nervous system encodes information about the physical parameters of cutaneous vibratory stimuli. The two sets of data indicated that the subjects derived information about the frequency of vibrotactile stimuli from the mean interval between action potentials in afferent nerve fibers activated by the stimulus. PMID- 1918627 TI - Effective attenuation of signals in noise under focused attention. AB - When attending to a tone at a given frequency, listeners are most sensitive to that tone and others within a restricted band of frequencies surrounding it. This region of enhanced sensitivity defines the attention band that was measured in two experiments using a modified version of the probe-signal method of Greenberg and Larkin [J. Acoust. Soc. Am. 44, 1513-1523 (1968)]. Experiment 1 showed that at five center frequencies, from 0.25 to 4.0 kHz, the shape of the attention band resembles that of the auditory filter as inferred from notched-noise masking experiments by other investigators. The width of the attention band is close to the critical band at higher frequencies, but only half as wide at 0.25 and 0.5 kHz. Experiment 2 produced psychometric functions for unattended probe tones at least 0.23 kHz away from a fully attended, 1-kHz target tone. From these functions, the effective attenuation, measured as the threshold difference between the 1-kHz target and the probes, was estimated to be 7 dB; the amount of attenuation appeared to be about the same regardless of how far the probe frequency was from the attended band. One interpretation of these results is that bands centered on the unattended tones contribute to the decision process with some small but measurable weight and are not entirely ignored. PMID- 1918628 TI - Performance of hearing-impaired persons on auditory enhancement tasks. AB - An auditory enhancement effect was evaluated in normal and hearing-impaired persons using a paradigm similar to that used by Viemeister and Bacon [J. Acoust. Soc. Am. 71, 1502-1507 (1982)]. Thresholds for a 2000-Hz probe were obtained in two forward-masking conditions: (1) the standard condition in which the masker was a four-component harmonic complex including 2000 Hz, and (2) the enhancing condition in which the same harmonic complex except for the exclusion of the 2000 Hz component preceded the four-component masker. In addition, enhancement for speech was evaluated by asking subjects to identify flat-spectrum harmonic complexes that were preceded by inverse vowel spectra. Finally, suppression effects were evaluated by measuring forward-masked thresholds for a 2000-Hz probe as a function of suppressor frequency added to a 2000-Hz masker. Across all subjects, there was evidence of enhancement and better vowel recognition in those persons who also demonstrated evidence of suppression; however, two of the normal hearing persons demonstrated reduced enhancement yet normal suppression effects. PMID- 1918629 TI - Effect of different types of auditory stimulation on vowel formant frequencies in multichannel cochlear implant users. AB - Two experiments investigating the effects of auditory stimulation delivered via a Nucleus multichannel cochlear implant upon vowel production in adventitiously deafened adult speakers are reported. The first experiment contrasts vowel formant frequencies produced without auditory stimulation (implant processor OFF) to those produced with auditory stimulation (processor ON). Significant shifts in second formant frequencies were observed for intermediate vowels produced without auditory stimulation; however, no significant shifts were observed for the point vowels. Higher first formant frequencies occurred in five of eight vowels when the processor was turned ON versus OFF. A second experiment contrasted productions of the word "head" produced with a FULL map, OFF condition, and a SINGLE channel condition that restricted the amount of auditory information received by the subjects. This experiment revealed significant shifts in second formant frequencies between FULL map utterances and the other conditions. No significant differences in second formant frequencies were observed between SINGLE channel and OFF conditions. These data suggest auditory feedback information may be used to adjust the articulation of some speech sounds. PMID- 1918630 TI - On the interpretability of speech/nonspeech comparisons: a reply to Fowler. AB - Fowler [J. Acoust. Soc. Am. 88, 1236-1249 (1990)] makes a set of claims on the basis of which she denies the general interpretability of experiments that compare the perception of speech sounds to the perception of acoustically analogous nonspeech sound. She also challenges a specific auditory hypothesis offered by Diehl and Walsh [J. Acoust. Soc. Am. 85, 2154-2164 (1989)] to explain the stimulus-length effect in the perception of stops and glides. It will be argued that her conclusions are unwarranted. PMID- 1918631 TI - Auditory perception is not special: we see the world, we feel the world, we hear the world. AB - The literature on "contrast" provides no evidence that durational contrast should occur in the speech and nonsence signals used in research cited by Diehl et al. [J. Acoust. Soc. Am. 89, 2905-2909 (1991)]. Moreover, there is evidence that, in comparable signals, it does not occur. Accordingly, their own account of the collection of findings on rate normalization is not viable. Their comments on my research do not imperil my interpretation of it or challenge my criticism that classification judgments of acoustically analogous speech and nonsense signals do not permit interpretation, by themselves, in terms of underlying auditory-system mechanisms. Their arguments that in auditory perception, uniquely, we hear proximal stimulation, not its physical causal sources, is implausible. Their theoretical perspective generally, I argue, is unrealistic. PMID- 1918632 TI - Effect of silence duration in intervocalic velar plosive on voicing perception for normal and hearing-impaired subjects. AB - For normally hearing subjects shortening the silence duration of an intervocalic voiceless plosive induces a misperception of voicing. The time boundary for this effect is about 60 ms, which corresponds to a possible forward masking effect at the frequency of voicing. If recovery from masking is indeed involved, hearing impaired subjects, who may have prolonged forward masking, can be expected to show abnormally long time boundary for voicing misperception. This study investigated the perception of voicing of an intervocalic plosive for a natural speech sample "aka" as a function of occlusive silence duration for normally hearing and hearing-impaired subjects. To investigate a correlation with forward masking, a second test was performed on the subjects. The same first a of the "aka" was selected and at its end was concatenated a voiced murmur taken from an "aga" elocution from the same speaker, and the minimum duration of the voiced murmur necessary for it to be perceived was measured. About half of the hearing impaired subjects needed an abnormally long silence duration to avoid voicing misperception. The data indicate a significant correlation between the results of the two tests with a slope of regression line close to unity, and thus support the hypothesis of a voicing perception ruled by recovery from forward masking. Increase in silence duration of voiceless plosives might then be a beneficial acoustical processing for some hearing-impaired subjects. PMID- 1918633 TI - Evaluating the articulation index for auditory-visual input. AB - An investigation of the auditory-visual (AV) articulation index (AI) correction procedure outlined in the ANSI standard [ANSI S3.5-1969 (R1986)] was made by evaluating auditory (A), visual (V), and auditory-visual sentence identification for both wideband speech degraded by additive noise and a variety of bandpass filtered speech conditions presented in quiet and in noise. When the data for each of the different listening conditions were averaged across talkers and subjects, the procedure outlined in the standard was fairly well supported, although deviations from the predicted AV score were noted for individual subjects as well as individual talkers. For filtered speech signals with AIA less than 0.25, there was a tendency for the standard to underpredict AV scores. Conversely, for signals with AIA greater than 0.25, the standard consistently overpredicted AV scores. Additionally, synergistic effects, where the AIA obtained from the combination of different bandpass-filtered conditions was greater than the sum of the individual AIA's, were observed for all nonadjacent filter-band combinations (e.g., the addition of a low-pass band with a 630-Hz cutoff and a high-pass band with a 3150-Hz cutoff). These latter deviations from the standard violate the basic assumption of additivity stated by Articulation Theory, but are consistent with earlier reports by Pollack [I. Pollack, J. Acoust. Soc. Am. 20, 259-266 (1948)], Licklider [J. C. R. Licklider, Psychology: A Study of a Science, Vol. 1, edited by S. Koch (McGraw-Hill, New York, 1959), pp. 41-144], and Kryter [K. D. Kryter, J. Acoust. Soc. Am. 32, 547-556 (1960)]. PMID- 1918635 TI - Ultrasound speckle analysis based on the K distribution. AB - The departure of speckle magnitude from Rayleigh statistics was applied to examine insonated phantoms with both low and high concentrations of scatterers. A mathematical model, the K distribution of Jakeman, was used to characterize non Rayleigh statistics. This model contains a parameter, alpha, which characterizes the clustering of the scattering sites in a medium. It is shown from phantom experiments that alpha is linearly proportional to the log-scaled scatterer concentration in a range from about 1 to 30 scatterers per sample volume. PMID- 1918634 TI - Cross-language speech perception in adults: phonemic, phonetic, and acoustic contributions. AB - Cross-language studies have shown that foreign consonant contrasts vary in the degree of perceptual difficulty which they present adult non-native listeners. Phonemic, phonetic, and acoustic factors have been considered important in accounting for this variability. These factors were examined by comparing English listeners' perception of the Hindi retroflex versus dental place-of-articulation contrast in four different voicing contexts: voiceless unaspirated, breathy voiced, voiceless aspirated, and prevoiced. Differences in perceptual difficulty of the four contrasts were predicted based on (1) phonemic status (the functional status of the contrast in the listeners' native phonology), (2) phonetic experience (as allophones or free variants), and (3) differences in acoustic salience related to voicing. Performance was not "nativelike" for any of the four contrasts; however, significant differences in perceptual difficulty among the four contrasts were evident. Perceptual differences were correlated with both acoustic salience of place cues and subjects' descriptions of their assimilation strategies. PMID- 1918636 TI - Comodulation masking release and the masking-level difference. AB - An experiment was performed to determine if the mechanism that mediates comodulation masking release (CMR) is associated with that used to improve detection by the masking-level difference (MLD). The experiment consisted of first improving detectability of a masked diotic tone burst by adding a synchronous noise band at another frequency region (CMR), and then measuring an MLD in the usual manner, by inverting the tone-burst signal to one ear. Results indicate that a substantial MLD can be measured for a signal whose detectability has already been improved by CMR. However, that MLD (9 dB) is smaller than that measured in random noise (14 dB). Put another way, a small CMR (4 dB) can be produced even when the detectability of a stimulus has already been improved due to the MLD. These data are in general agreement with those of Hall et al. [J. Acoust. Soc. Am. 83, 1839-1845 (1988)] and Schooneveldt and Moore [J. Acoust. Soc. Am. 85, 262-272 (1989)]. PMID- 1918637 TI - Program of the 122nd meeting of the Acoustical Society of America. Houston, Texas, 4-8 November 1991. Abstracts. PMID- 1918638 TI - Children could benefit from an expansion in day care services in British hospitals. PMID- 1918640 TI - Analysed interaction in a children's oncology clinic: the child's view and parent's opinion of the effect of medical encounters. AB - Every effort is made to provide children affected by cancer-related illness with advanced medical care. This theory-developing, hypotheses-generating study focused on the child's view of the service provided in an oncology clinic. The methodology included interviews, observations of medical consultations and children's drawings. It also sought the parents' opinion of the effect of an impending appointment on the child's behaviour. The population for this ideographic research consisted of a convenience sample of 10 children over the age of 5 years, attending an oncology clinic which served a medium-sized city and its surrounding area. Quantitative and qualitative data were collected from semi structured interviews, participant observations, transcribed audio-tape recordings and gaze interaction charts. Data were analysed using grounded theory. The medical interview was not acknowledged as being very significant by the children: their conscious attention centred on peers and play activities. The data also suggest that clinic visits are more acceptable for children when staff invest personal attention, give appropriate adequate explanations and handle children sensitively. Behaviour changes before appointments were reported by parents to be more prevalent in children who received less positive regard from the health team. Clinic observations and transcripts demonstrated the doctor's 'dominant role' during consultations. Interaction with the child centred around the examination and was frequently interrupted. A more extensive study would confirm or refute these provisional findings. PMID- 1918639 TI - A study of role negotiation between nurses and the parents of hospitalized children. AB - The role of the parent of a hospitalized child has changed considerably over the past 30 years. Where parents were previously expected to had responsibility for care over to their child's nurses, there is now an expectation that parents will be extensively involved in the care of their hospitalized children. The negotiation of roles between nurses and parents has been advocated by workers concerned about conflicts between nurses and parents. However, it is not known whether such negotiation takes place between nurses and parents. It is clear that power is not evenly distributed between nurses and parents: issues of territory, stress, anxiety, uncertainty, control and conflicts arising from parental competence all place the parent in a weaker position. It is argued that the nurse holds the initiative in the decision about whether negotiation takes place. A small study is described in which nurses were invited to describes their response to their perception that a parent wanted to increase or decrease her or his involvement in her or his child's care. The critical incident technique (Flanagan 1954) was used to collect data. Nurses' responses were categorized into categories of 'encouragement', 'explanation/advice' and 'negotiation'. Responses were then placed in more specific subcategories. The inter-rater reliability of the categorization was measured. Owing to the limitations of the study, the results can only be regarded as suggestive. Nevertheless, significant association was found between the category of response and the grade of staff, with a stratified pattern of category of response demonstrated. The implications of the study for future research are discussed. PMID- 1918641 TI - The epidemiology of inflammatory bowel disease in children: a pilot project. AB - A major study about the epidemiology of inflammatory bowel disease in children was planned. A pilot study of pre-morbid variables among 42 children with the disease was undertaken. Conducting a pilot study was an essential component of the research process, both in refining the data collection instrument and in maximizing the use of technology. Results of the pilot study are described and the way in which they were used to prepare a better major study are discussed. PMID- 1918642 TI - A decade of research in locus of control: what have we learned? AB - Locus of control has received considerable attention from nurse researchers over the past decade. A review of nursing studies related to locus of control reveals that the collective results of this research have yielded little information that is useful for nursing practice. It is noted that many of the criticisms levelled at locus of control research at the beginning of the decade are still problematic. For example; most studies are correlational in design; instruments used to measure the construct suffer from reliability and validity problems; researchers have failed in many cases to consider the multidimensional nature of the construct; and in most studies the value of the reinforcer is ignored. If future research in this area is to lead to useful results, nurse researchers must be prepared to move to experimental designs, and must pay greater attention to issues of reliability and validity. PMID- 1918643 TI - Changes in nursing students' knowledge about and attitudes toward research following an undergraduate research course. AB - This study examined changes in baccalaureate nursing students' attitudes toward and knowledge about research, following completion of a research course. The teaching methods used in the course included having students critique research articles, complete objective examinations, and work in small groups to develop research proposals. The sample of 54 students completed a pretest and two post tests measuring research knowledge, and a pretest and one post-test measuring research attitudes. The pretest was administered at the beginning of the research course, and the first post-test was administered at the end of the course. The second post-test was administered during the students' last semester in the nursing programme. Students reported more positive attitudes toward research at the end of the programme than at the beginning of the course. Knowledge scores were significantly higher at the end of the course than at the beginning of the course or at the end of the programme. There was no differences in knowledge scores on the pretest and on the second post-test. The findings raise questions about the effectiveness of traditional research curricula in preparing baccalaureate nursing students to be competent research consumers. PMID- 1918644 TI - Nurses' perceptions of their problem-solving ability. AB - A problem-solving approach to nursing practice has been advocated in the nursing literature for some time. However, the extent to which nurses perceive themselves as capable problem solvers or improve their problem-solving ability during their nursing education is not generally known. The purpose of this study was to determine the relationship between nurses' perceptions of their problem-solving ability and their course of study. The Problem-Solving Inventory (PSI) was developed by Heppner and colleagues (1982) to assess attitudes towards and perceptions of problem-solving behaviour. The instrument provides a global appraisal of oneself as a problem solver and assesses perceptions of problem solving ability. In this study, data were collected from 67 pre and post registration nursing students in two phases; during their course and on completion of their course. Data from each phase were compared to identify changes in perception of problem-solving behaviour over time. While there was no overall improvement in perceptions of problem-solving ability by phase 2, confidence in problem solving had improved significantly (P less than 0.01). There were improvements according to age, experience, and course being undertaken for the likelihood of approaching rather than avoiding problems, and having personal control over problem solving. PMID- 1918645 TI - Project 2000: the role of resistance in the process of professional growth. AB - This paper attempts to use the work of Peter Marris on loss and change to provide a theoretical perspective on the role of resistance in the process of professional growth. Nurse education is highlighted as an area of radical change with the implementation of Project 2000 in the United Kingdom. Early data generated by exploratory work in one Project 2000 demonstration district are used to illustrate the potential emergence of areas of resistance to major educational reform. It is argued that resistance to change has an adaptive function and is a necessary precursor to professional growth. It is not necessarily indicative of intransigence but rather should be seen as part of any process of adaptation to changes which might undermine the validity of past systems of understanding the world in which we live. PMID- 1918646 TI - Women's mid-life experience: an evolving consciousness of self and children. AB - This paper describes a hermeneutical and phenomenological research study of the mid-life spiritual experience of 10 women who are members of the United Church of Canada. Based on in-depth, face-to-face interviews, the paper describes the first of two simultaneous and interrelated experiences: an evolving consciousness of self and children. The five invariant themes that emerge point to a need for an expanded framework of human development that takes fuller account of women's experience and spirituality. PMID- 1918647 TI - The work of a specialist AIDS home support team: the views and experiences of patients using the service. AB - The work of a specialist AIDS home support team whose role is to ensure continuity of care between hospital and community for patients with HIV infection is viewed from the patients' perspective. Information comes from a wider interview study in which 265 gay men positive for HIV were asked about their perceptions of and satisfaction with a variety of different services. Of the group, 119 (46%) reported involvement with the home support team. The team was seen as providing links between patients, the hospital and the community, as well as offering security for those who expected to need help in the future. For the most part, the team were seen in a favourable light when compared to other professionals and 53% felt they received a considerable amount of reassurance and support from them. PMID- 1918648 TI - Patient perspectives of diabetes care and education. AB - Educating and supporting patients in managing their daily life with diabetes mellitus are important goals of diabetes care today. These goals demand not only good medical knowledge but also good communication skills in the members of the diabetes care team and in the patients. Continuity and accessibility are naturally factors influencing the communication between the patients and the care team. This study, based on 55 interviews with well-experienced insulin-dependent diabetic patients, shows further that the contacts between the diabetes care system and the patient are often only superficial and in practice mainly related to the patient's metabolic control. Patients with good or acceptable metabolic control experience positive feed-back from the care team, while those with unsatisfactory or unacceptable metabolic control do not receive positive response and support to the same degree. The patients want to be permitted to be responsible for themselves and need support from the care team in order to accomplish this. From the patient's perspective, the diabetes education consists of an overwhelming amount of new information which often is presented on only one occasion. The patients want the education to be on an acceptable but minimum level and to be a continuous process that is applicable in practice. PMID- 1918649 TI - Student nurses' attitudes to psychiatry: the influence of training and personality. AB - Fifty-one second-year students completed the Attitudes to Treatment Questionnaire (ATQ), the Conservatism Scale (CS), the Defence Style Questionnaire (DSQ) and an open-ended questionnaire before and after components of their psychiatric training programme, which included a 1-week placement in a psychiatric hospital. CS scores indicated that the nurses were moderately conservative. ATQ scores and CS scores correlated significantly, with the more conservative nurses reporting more traditional attitudes to psychiatric nursing. ATQ scores fell significantly after psychiatric hospital placement, indicating more progressive attitudes. Mean scores on the DSQ were within normal limits, although men scored significantly higher than women on the Immature Defences Scale immediately after placement. The open-ended questionnaire revealed mainly positive comments about the psychiatric hospital placement. Almost half the nurses expressed surprise at the relaxed, informal atmosphere on the wards, and as many stated that personal interaction with the patients rapidly removed any stereotyped attitudes that they held previously. Over 40% of nurses stated that the patients were much less aggressive or dangerous than they had expected, although nearly 20% said they were concerned about the levels of aggression that they observed. PMID- 1918650 TI - Personality hardiness, ways of coping, social support and burnout in critical care nurses. AB - Hardiness, ways of coping, social support and burnout in 103 critical care nurses were addressed in this study. Work-related and nonwork-related social support and hardiness were negatively related to burnout. Use of emotion-focused coping was positively correlated with burnout while hardiness was negatively related to the use of emotion-focused coping and positively related to both types of social support. After controlling for working nights, social support, hardiness, emotion focused coping and problem-focused coping accounted for 44% of the variance in burnout scores. PMID- 1918651 TI - Conceptual frameworks and patterns of nursing curriculum. AB - Common concepts of conceptual frameworks and curriculum patterns are identified by studying all 18 English-speaking, generic baccalaureate nursing programmes in Canada. Four identified curriculum patterns use client systems, health-illness, growth and development, and nursing roles as the primary curriculum organizer to sequence programme courses. The nursing programmes commonly use nursing process, followed by growth and development, human needs, and family as secondary organizers to structure contents of programme course. Identifying a curriculum by its organizers is useful to curriculum practice and research. Nursing faculty can use the identified organizers as primary or secondary organizers in designing, changing or evaluating their curriculum. It is also possible to use a nursing model with the identified organizers for an effective curriculum structure. Research studies on conceptual frameworks could use primary and secondary organizers to compare strength and weakness among different nursing curriculum structures. PMID- 1918652 TI - The professional values of English nursing undergraduates. AB - The purpose of the study was to examine and describe what English nursing undergraduates internalize as professional values. The method was qualitative; specifically, a grounded theory approach was used. The sample comprised 12 senior baccalaureate nursing students from two educational institutions in the north of England. Informants were volunteers who gave informed consent having been briefed on the purposes of the study and how their confidentiality would be protected. Data were collected through audio-taped interviews and the constant comparative method was used to analyse data. The findings revealed that informants perceived two concepts as central to their professional values. These were respect for patients and 'caring about the little things'. They valued the rights of patients to be treated with respect, to know what was happening to them and to have a say in what happened to them. They described the 'little things' as 'an approach with patients that gets through to them'; 'getting out the mirror so they can see themselves'; 'fixing their water so they can reach it'; worrying about someone's dentures or the cat they left at home. They expected that their values would be in conflict with common hospital practice. They valued 'fitting in' and 'going along' but retained their own ideas and values until such time as these could be implemented. They perceived themselves as powerless to create change as new graduates. They believed the overwhelming power resided in the hospital system and the ward sister/charge nurse. They were not inclined toward a career in hospital nursing. PMID- 1918653 TI - The language of experiential learning. AB - Experiential learning has been advocated as a means of helping students to learn about aspects of nursing. This paper reports an analysis of two language styles identified during a research project that explored nurse tutors' and students' perceptions of experiential learning. Twelve nurse tutors and 12 student nurses were interviewed and the transcripts were analysed using a modified grounded theory approach. The aspect of the findings reported here is that of the emergence of two 'language styles' used by some of the writers and practitioners in the field of experiential learning. It is suggested that those language styles may form a 'culture isogloss' or barrier between tutors and students. PMID- 1918654 TI - Can future suicidal behaviour in depressed patients be predicted? AB - The determinants of suicidal behaviour over 18 years were examined in a series of 89 depressed in-patients, using index data on clinical features, personality, and history of past loss. Seven variables were selected from univariate analyses and their relationship with (1) the presence or absence, (2) frequency, (3) intent, and (4) medical threat of suicidal behaviour was then explored by generalised linear modelling. Severe dysphoria, past alcoholism and chronic physical illness were most predictive of suicidal attempting; however, different variables predicted the frequency, degree of intent and severity of medical threat of subsequent suicidal attempts. Thus, our results suggest that different aspects of long-term suicidal behaviour have different determinants. PMID- 1918655 TI - Fluoxetine vs. clomipramine in depressed patients: a controlled multicentre trial. AB - A sample of 120 patients, all of whom met DSM-III criteria for major unipolar depressive disorder, were randomly allocated to two treatment groups. Sixty patients were treated with fluoxetine and 60 with clomipramine during a 6-week period. No significant difference was found in antidepressant efficacy, with improvement occurring on both drugs. Important differences were found in the side effects profile of each group, their incidence being significantly lower and tending to disappear during the course of treatment in the group of patients treated with fluoxetine. PMID- 1918656 TI - Identification of minor affective disorders and implications for psychopharmacotherapy. AB - Five hundred general practice patients with functional complaints were studied with the Polydiagnostic Interview (PODI) to see whether DSM-IIIR criteria were able to specify affective disorders satisfactorily. Almost one third of the patients received the diagnosis of depression not otherwise specified (NOS). When Research Diagnostic Criteria were applied to these patients more than 70% received specific diagnoses. A modification of DSM-IIIR algorithms enabled us to further specify diagnoses in subjects with depression NOS. On the 17-item Hamilton Depression Scale many of these patients reached scores of 13 or more which is severe enough to justify a therapy trial with antidepressants. PMID- 1918657 TI - Distinguishing psychotic and non-psychotic melancholia. AB - To examine the necessary and sufficient status of delusions and hallucinations as clinical features of psychotic (delusional) depression, we studied a consecutive sample of 137 patients meeting DSM-III, RDC and our clinical criteria for endogenous depression/melancholia, of whom 35 had delusions and/or hallucinations, and represented our putative 'psychotic depressives' (PDs). The PDs were contrasted with the remaining 'endogenous depressives' (the EDs), and an age- and sex-matched subsample of the latter, the MEDs. Univariate and multivariate analyses of clinical features established that, in addition to the presence of delusions and/or hallucinations, the PDs could be distinguished in particular by severe psychomotor disturbance, as well as by sustained and unvarying depressive content, the absence of any diurnal mood variation and by constipation. Latent class analyses suggested that overt psychotic features (such as delusions and hallucinations) were sufficient but not necessary for a subject to be assigned to the 'psychotic' latent class, and a subsequent chart review suggested that, in some PDs actual psychotic features may not be able to be elicited because of severe psychomotor change, suggesting that clinical reliance on eliciting delusions or hallucinations may result in a number of 'masked psychotic depressives' escaping valid diagnosis. PMID- 1918658 TI - Relationship between observed NMR changes and brain water content following electroconvulsive stimulation in the rat. AB - The administration of electroconvulsive stimuli to anaesthetised rats results in changes in the relaxation times and water content of grey and white matter, but not in mid brain, hind brain or cerebellum. White matter changes occur in both T1 and T2, are biphasic in character and related to water content. Grey matter changes are confined to T1 and water content only. It is suggested that these changes are related to altered compartmentalisation of water, manifesting in a different manner in the two tissues probably due to their different cellular and biochemical composition. PMID- 1918659 TI - The effects of lithium discontinuation and the non-effect of oral inositol upon thyroid hormones and cortisol in patients with bipolar affective disorder. AB - Thyroid and adrenal function was assessed in euthymic bipolar patients, stable on prophylactic lithium for at least 1 year, before and after lithium discontinuation in a randomised double-blind placebo-controlled trial. All hormonal measurements were within the reference range, but a significant increase (P less than 0.001) in plasma thyroxine (T4) levels and a decrease (P less than 0.01) in TSH levels were observed 1 month after lithium withdrawal; cortisol concentrations showed a non-significant decrease in the same period. No relationship could be demonstrated between the magnitude of the change in hormone levels and the probability of relapse of manic symptoms. In the second part of this study, inositol was added for 11 days to the diets of bipolar patients being treated with prophylactic lithium and normal controls. No modification was shown in T4 and TSH in either group before or after inositol administration. Inositol did not alleviate other side-effects such as tremor and thirst in the patient group. This result suggests that short-term dietary inositol is not equivalent to lithium withdrawal and is of no value in reducing hormonal and other adverse effects of lithium prophylaxis. PMID- 1918660 TI - Major depression in panic disorder patients with comorbid social phobia. AB - Rates of depression among panic disorder patients are particularly elevated in patients with comorbid social phobia. However, it is unclear whether this association is specific to social phobia, or whether any comorbid anxiety disorder increases the risk of depression. We assessed 100 panic disorder patients and found a significantly higher incidence of lifetime major depression for panic patients with comorbid social phobia or generalized anxiety disorder (GAD). Panic patients with comorbid social phobia had significantly higher scores on measures of dysfunctional attitudes and lower scores on measures of assertiveness; these variables may mediate the link between social phobia and depression in this population. PMID- 1918661 TI - Emotion and science. PMID- 1918663 TI - The data bank. PMID- 1918664 TI - Autonomy could be dangerous. PMID- 1918662 TI - Dentin bonding systems. PMID- 1918665 TI - Using antimicrobial agents to manage periodontal diseases. AB - Periodontal diseases are bacterial infections and anti-microbials have been shown to be useful in their treatment and prevention. State-of-the-art treatment of refractory forms of destructive periodontal disease presently includes adjunctive use of systemic antibiotics directed to eliminating or suppressing pathogenic subgingival bacteria. Also, local application of antimicrobials by subgingival deposition or their use as irrigants during periodontal therapy are soon likely to be major components of anti-infective management of periodontal diseases. A new approach to anti-infective periodontal therapy combines ultrasonic surgical debridement with antimicrobial irrigation. PMID- 1918666 TI - A life in science. Dr. Genco receives Gold Medal for research. PMID- 1918667 TI - Dental caries: is it an extinct disease? AB - Although almost half of U.S. children aged 5 to 17 years are caries-free, less than 5 percent of adults 18 to 65 years have no tooth decay. It appears that caries attacks persist unrelentingly throughout life. Continuous caries prevention, therefore, is essential, especially in an aging population. PMID- 1918668 TI - Treating TM disorders: a survey on diagnosis, etiology and management. AB - This survey of five dental groups revealed that the dental profession still is far from reaching a consensus about temporomandibular disorders. Despite a great deal of research that has clarified many issues in this field, clinicians often cling to outdated concepts and practices. However, many respondents did give answers that demonstrated their awareness of modern TMD diagnostic and treatment guidelines. PMID- 1918669 TI - Dental fluorosis in perspective. AB - The relationship between fluoride in drinking water, caries and fluorosis was established 50 years ago. But additional sources that duplicate or expand fluoride benefits may not carry the same low risk for fluorosis and should be monitored. PMID- 1918670 TI - HIV cells found in saliva. PMID- 1918671 TI - Treating the cracked tooth with a full crown. AB - Twenty-eight teeth diagnosed as having a crack were immediately treated with full coverage acrylic resin crowns. Twenty-five of these teeth became asymptomatic after full coverage acrylic crown placement and continued to be asymptomatic one year after restoration. PMID- 1918672 TI - Medication can induce severe ulcerations. AB - Nonsteroidal antiinflammatory drugs can cause oral ulcers. In this case, discontinuing piroxicam, a nonsteroidal anti-inflammatory drug, and starting a palliative treatment plan helped resolve a patient's ulcers. PMID- 1918673 TI - Microfills vs. hybrids. Is there a universal composite resin? AB - An impressive positive evolution has taken place in restorative resins in the past 20 years. Although the types of resin used have not changed significantly, the fillers used in resins have changed enormously. Filler size has changed from particles that approached the size of table salt (over 100 microns) to today's submicron particle size. This article compares types of restorative resins for anterior and posterior use. PMID- 1918675 TI - Hygiene enrollments rising. An end to the shortage may be in sight. PMID- 1918674 TI - Reviewing pulp treatment for primary teeth. AB - Deficiencies of pulpotomy and pulpectomy treatment of primary teeth have promoted considerable laboratory and clinical research. Some of these findings and their implications are reviewed. PMID- 1918676 TI - Dealing with dentistry's image dilemma. PMID- 1918677 TI - Fair pay: an approach to staff compensation. PMID- 1918678 TI - States astir over AIDS, amalgam. Fluoride mainly a local issue. PMID- 1918679 TI - Disclosing HIV status. Ethical issues explored. PMID- 1918680 TI - Porcelain repair materials. Council on Dental Materials, Instruments and Equipment. AB - Porcelain repair materials, when properly chosen and used, provide some bond strength in bonding to porcelain. The bond strength is decreased by thermocycling and long-term storage in water. Currently available products are affected differently by these conditions. Surface roughening by rotary instruments and chemical etching by hydrofluoric acid or APF enhances the bond strength. The long term clinical performance of the porcelain repair materials is not well documented. The council is preparing guidelines to evaluate these materials under the Acceptance Programs of the council. These guidelines will include requiring information on the laboratory and chemical data on these products to demonstrate their safety and efficacy. PMID- 1918681 TI - Dealing with risks in the dental office. PMID- 1918682 TI - Informed consent. Does doctrine apply to HIV, amalgam, fluoride? PMID- 1918683 TI - Management of the oral lesions of HIV infection. AB - AIDS and other expressions of HIV infection continue to present ever-increasing challenges to the health professions, including dentistry. Patients with oral manifestations of HIV disease present or are referred to dental practitioners for the diagnosis and treatment of their oral lesions. This review briefly summarizes the management approaches currently adopted at the Oral AIDS Center, University of California, San Francisco. PMID- 1918684 TI - State-of-the-art infection control in dentistry. AB - This paper defines infection control in dentistry as it exists in 1991 and makes some predictions about the future of this area. A total of 21 items form the basis of a comprehensive infection control program. PMID- 1918685 TI - A matter of policy. Health groups face the AIDS crisis. PMID- 1918686 TI - Dental amalgam and mercury. AB - This paper looks at the issues of the current amalgam controversy: the daily dose of mercury from amalgam, hypersensitivity to mercury, claims of adverse effects from amalgam mercury and alleged overnight "cures." In addition, the toxicity and allergenicity of the proposed alternative materials are examined with the same kind of scrutiny applied by the anti-amalgam group to dental amalgam. PMID- 1918687 TI - Amalgam hazards. An assessment of research. AB - Although mercury vapor in high concentration can have deleterious effects on several organ systems, there is no evidence of risk at the levels generated by chewing with amalgam restorations. Epidemiological studies relating amalgam exposure to health outcomes are recommended, however, to provide the profession and the public a full sense of security. PMID- 1918688 TI - Dental amalgam. Designs for research in human populations. AB - Questions have been raised about the safety of dental amalgam. The main point of contention is whether the mercury contained in dental restorations is released in sufficient quantities to pose a public health hazard. Most scientists agree that current evidence is not sufficient to show that amalgam restorations pose a general health threat. But researchers on both sides of this debate agree that much remains to be learned about any potential toxicity of dental amalgam--an issue serious enough to merit additional research. PMID- 1918690 TI - The future of fluoride. An update one year after the National Toxicology Program Study. PMID- 1918691 TI - Too much of a good thing? Questions about fluorosis explored. PMID- 1918692 TI - Infection control. Some significant loopholes. PMID- 1918689 TI - Is restorative dentistry on its way out? PMID- 1918693 TI - ACC/AHA guidelines for cardiac catheterization and cardiac catheterization laboratories. American College of Cardiology/American Heart Association Ad Hoc Task Force on Cardiac Catheterization. PMID- 1918694 TI - Clinical, angiographic and procedural correlates of quantitative coronary dimensions after directional coronary atherectomy. AB - To define the clinical, angiographic and procedural correlates of quantitative coronary dimensions after directional coronary atherectomy, 400 lesions in 378 patients were analyzed with use of qualitative morphologic and quantitative angiographic methods. Successful atherectomy, defined by a less than 75% residual area stenosis, tissue retrieval and the absence of in-hospital ischemic complications, was performed in 351 lesions (87.7%). After atherectomy, minimal cross-sectional area increased from 1.2 +/- 1.1 to 6.6 +/- 4.4 mm2 (p less than 0.001) and percent area stenosis was reduced from 87 +/- 10% to 31 +/- 42% (p less than 0.001). By univariate analysis, device size (p less than 0.001) and left circumflex artery lesion location (p = 0.004) were associated with a larger final minimal cross-sectional area. Conversely, restenotic lesion (p = 0.002), lesion length greater than or equal to 10 mm (p = 0.018) and lesion calcification (p = 0.035) were quantitatively associated with a smaller final minimum cross sectional area. With use of stepwise multivariate analysis to control for the reference area, atherectomy device size (p = 0.003) and left circumflex lesion location (p = 0.007) were independently associated with a larger final minimal cross-sectional area, whereas restenotic lesion (p = 0.010), diffuse proximal disease (p = 0.033), lesion length greater than or equal to 10 mm (p = 0.026) and lesion calcification (p = 0.081) were significantly correlated with a smaller final minimal cross-sectional area. The number of specimens excised, the number of atherectomy passes and atherectomy balloon inflation pressure did not correlate with the final minimal cross-sectional area. Thus, directional atherectomy results in marked improvement of coronary lumen dimensions, at least in part correlated with the presence of certain clinical, angiographic and procedural factors at the time of atherectomy. PMID- 1918695 TI - Echocardiographic assessment of patients with infectious endocarditis: prediction of risk for complications. AB - To enhance the echocardiographic identification of high risk lesions in patients with infectious endocarditis, the medical records and two-dimensional echocardiograms of 204 patients with this condition were analyzed. The occurrence of specific clinical complications was recorded and vegetations were assessed with respect to predetermined morphologic characteristics. The overall complication rates were roughly equivalent for patients with mitral (53%), aortic (62%), tricuspid (77%) and prosthetic valve (61%) vegetations, as well as for those with nonspecific valvular changes but no discrete vegetations (57%), although the distribution of specific complications varied considerably among these groups. There were significantly fewer complications in patients without discernible valvular abnormalities (27%). In native left-sided valve endocarditis, vegetation size, extent, mobility and consistency were all found to be significant univariate predictors of complications. In multivariate analysis, vegetation size, extent and mobility emerged as optimal predictors and an echocardiographic score based on these factors predicted the occurrence of complications with 70% sensitivity and 92% specificity in mitral valve endocarditis and with 76% sensitivity and 62% specificity in aortic valve endocarditis. PMID- 1918696 TI - Exacerbation of ventricular arrhythmias during the postoperative period after implantation of an automatic defibrillator. AB - The postoperative course of 68 consecutive patients treated with an implantable defibrillator during the period from 1982 through 1990 was studied. In 46 patients (group 1), no concomitant surgery was performed during the implantation. In 22 patients (group 2), concomitant surgery (coronary artery bypass [n = 12], valve replacement [n = 3] or arrhythmia surgery [n = 7]) was performed. All patients in group 1 were clinically stable before surgery, receiving an antiarrhythmic regimen chosen by serial drug testings. The same regimen was continued postoperatively. Eight of the 46 patients in group 1 whose condition had been stable in the hospital for 19 +/- 25 days preoperatively developed multiple episodes of sustained ventricular tachycardia 4 +/- 9 days after implantation while receiving the same antiarrhythmic regimen. Although the exacerbation was transient in some patients, six required different antiarrhythmic therapy and one eventually died. Two additional patients had frequent and prolonged episodes of nonsustained ventricular tachycardia that could trigger the defibrillator, requiring changes in the antiarrhythmic regimen. Another patient had progressive cardiac failure and died on day 5. A marked (sevenfold) increase in asymptomatic ventricular arrhythmias was noted in 42% of the remaining 35 patients. In group 2 (combined surgery), one patient developed refractory ventricular tachycardia 3 days postoperatively and died on that day. Three patients developed frequent nonsustained ventricular tachycardia postoperatively, requiring changes in the antiarrhythmic regimen. The overall surgical mortality rate was 4.4% (4.3% in group 1 and 4.5% in group 2) and was due to refractory ventricular tachycardia in two patients and cardiac failure in one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918697 TI - Uncomplicated first myocardial infarction: strategy for comprehensive prognostic studies. AB - To evaluate the prognostic role of combined cardiac studies (submaximal exercise test, thallium-201 scintigraphy, radionuclide exercise ventriculography, two dimensional echocardiography, Holter monitoring and cardiac catheterization) in patients with a first acute myocardial infarction without complications during hospital admission, 115 consecutive patients aged less than 65 years were prospectively evaluated. The studies were carried out before hospital discharge and the patients were then clinically followed up for 12 months. During the follow-up period, 69 patients (60%) developed complications, which were severe in 23 (20%). Half of all complications and 70% of severe complications developed during the 1st follow-up month. Logistic regression analysis disclosed that the combination of studies with the highest predictive power for complications (probability of complications 99%) and severe complications (probability of severe complications 95%) was the association of exercise test + thallium-201 + echocardiogram. Four decision models (exercise test + echocardiography, exercise test + radionuclide ventriculography, thallium-201 scintigraphy + echocardiography, thallium-201 scintigraphy + radionuclide ventriculography) allowed the stratification of all patients in a particular risk category (high, intermediate or low). The best decision model was the association of thallium-201 scintigraphy + radionuclide ventriculography (probability of complications if both tests were positive 84%; probability of absence of severe complications if both tests were negative 88%), but there were no significant differences with the other models. Any association of a test detecting residual ischemia or functional capacity, or both (exercise test or thallium-201) and a test assessing ventricular function (echocardiography or radionuclide ventriculography) results in significant prognostic information in patients with an uncomplicated first acute myocardial infarction. Additional cardiac catheterization does not improve the predictive power of noninvasive studies, which should ideally be performed before hospital discharge because most complications develop during the 1st follow-up month. PMID- 1918698 TI - What would I want to know if my dad had a heart attack? Good sense versus dollars and cents. PMID- 1918699 TI - Atrial septal aneurysm and stroke: a transesophageal echocardiographic study. AB - The prevalence and morphologic characteristics of atrial septal aneurysms identified by transesophageal echocardiography in 410 consecutive patients are described. Two groups of patients were compared: Group I consisted of 133 patients referred for evaluation of the potential source of an embolus and Group II consisted of 277 patients referred for other reasons. An atrial septal aneurysm was diagnosed by transesophageal echocardiography in 32 (8%) of the 410 patients. Surface echocardiography identified only 12 of these aneurysms. Atrial septal aneurysm was significantly more common in patients with stroke (20 [15%] of 133 vs. 12 [4%] of 277) (p less than 0.05); right to left shunting at the atrial level was demonstrated in 70% of patients in Group I and 75% of patients in Group II by saline contrast echocardiography. Four patients in Group I had an atrial septal defect with additional left to right flow. There was no difference between the two groups in aneurysm base width, total excursion or left atrial or right atrial excursion. However, Group I patients had a thinner atrial septal aneurysm than did Group II patients. It is concluded that an atrial septal aneurysm occurs commonly in patients with unexplained stroke, is more frequently detected by transesophageal echocardiography than by surface echocardiography and is usually associated with right to left atrial shunting. Treatment (anticoagulant therapy vs. surgery) of atrial septal aneurysm identified in stroke patients can be determined only by long-term follow-up studies. PMID- 1918700 TI - Primary restrictive cardiomyopathy: clinical and pathologic characteristics. AB - Twenty-four patients with restrictive cardiomyopathy were identified at St. Thomas' Hospital during a 17-year period. All had endomyocardial biopsy, but in two patients the biopsy specimens were small and nondiagnostic. Seven patients had amyloidosis and five had other specific heart muscle diseases. The remaining 10 patients with primary restrictive cardiomyopathy had myocyte hypertrophy or interstitial fibrosis, or both. Patients with primary restrictive cardiomyopathy presented earlier but survived longer after presentation than did those with amyloidosis. In each group, survival after cardiac catheterization was related to cardiac index but not to filling pressures. Primary restrictive cardiomyopathy was associated with complete heart block in four patients, two of whom had skeletal myopathy. One had a family history of dominantly inherited skeletal myopathy. Primary restrictive cardiomyopathy was present in a mother and daughter. Two other patients had a family history of heart failure, sudden death or complete heart block, alone or in combination, at a young age. Restrictive hemodynamics and complete heart block were present in patients even in the absence of significant fibrosis. The data suggest that primary restrictive cardiomyopathy may be a distinct myopathy with dominant inheritance and incomplete penetrance that is expressed morphologically as myocyte hypertrophy and interstitial fibrosis. Skeletal myopathy may be associated with the cardiomyopathy. PMID- 1918701 TI - Age-related alterations of Doppler left ventricular filling indexes in normal subjects are independent of left ventricular mass, heart rate, contractility and loading conditions. AB - The purpose of this study was to determine whether age-related alterations in Doppler diastolic filling indexes occur independent of cardiovascular disease and confounding physiologic variables. Ten old (62 to 73 years) and 10 young (21 to 32 years) healthy male volunteers were rigorously screened for cardiovascular disease and underwent comprehensive Doppler echocardiography, radionuclide ventriculography and invasive measurements of right heart and left atrial pressures. There were no differences between the two groups in the physiologic variables of left ventricular mass, volumes, ejection fraction, end-systolic wall stress, left atrial size, heart rate and right atrial, pulmonary artery, pulmonary capillary wedge and systemic arterial pressures. However, there were marked differences in Doppler left ventricular filling indexes. Compared with the young group, the old group had reduced peak early diastolic flow velocity (56 +/- 13 vs. 82 +/- 12 cm/s, p = 0.0002) and increased atrial diastolic flow velocity (59 +/- 14 vs. 43 +/- 10 cm/s, p = 0.009) and had a peak atrial/early flow velocity (A/E) ratio twice that of the young group (1.09 +/- 0.29 vs. 0.54 +/- 0.15, p less than 0.0001). Similar results were obtained for the time-velocity integrals of the peaks. Subjects in the old group also had a markedly reduced peak filling rate (274 +/- 62 vs. 448 +/- 152 ml/s, p = 0.004). In univariate and multivariate regression analyses, peak early and atrial flow velocities were not related to any of the physiologic variables measured once age was accounted for, although peak filling rate, a volumetric measure flow, was related to body surface area as well as age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918702 TI - Asynchronous (segmental early) relaxation impairs left ventricular filling in patients with coronary artery disease and normal systolic function. AB - Asynchronous segmental early relaxation, defined as a localized early segmental outward motion of the left ventricular endocardium during isovolumetric relaxation, has been associated with an altered left ventricular relaxation rate. To determine whether asynchronous segmental early relaxation also results in impaired left ventricular filling, early diastolic ventricular wall motion and Doppler-derived left ventricular filling indexes were examined in 25 patients with documented coronary artery disease and normal systolic function. Patients were further classified into two groups according to the presence (n = 15, group 1) or absence (n = 10, group 2) of asynchronous early relaxation at left ventriculography. A third group of 10 age-matched normal subjects served as a control group. No differences were observed between the two patient groups with coronary artery disease with respect to age, gender distribution, heart rate, left ventricular systolic and diastolic pressures or extent and severity of coronary artery disease. No differences in transmitral filling dynamics were observed between group 2 patients and age-matched control subjects. Conversely, group 1 patients had significantly lower peak early filling velocities (44 +/- 11 vs. 58 +/- 11 cm/s, p less than 0.01), larger atrial filling fraction (45 +/- 4% vs. 38 +/- 4%, p less than 0.001), lower ratio of early to late transmitral filling velocities (0.6 +/- 0.08 vs. 0.99 +/- 0.18, p less than 0.001) and a longer isovolumetric relaxation period (114 +/- 12 vs. 90 +/- 6 ms, p less than 0.001) compared with group 2 patients and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918704 TI - Diagnosis of ischemic heart disease with adenosine echocardiography. AB - To assess the feasibility, safety and diagnostic accuracy of adenosine infusion combined with echocardiography, 73 patients with suspected or known coronary artery disease underwent echocardiography at baseline and during a maximal intravenous adenosine infusion of 140 micrograms/kg per min. Compared with baseline values, adenosine caused an increase in heart rate, a decrease in systolic and diastolic blood pressure and a slight but significant increase in rate-pressure product. The echocardiographic images were digitized and randomly assigned in a quad-screen format for nonbiased interpretation. An ischemic response, defined as a new or worsening wall motion abnormality, developed in 25 patients; a fixed wall motion abnormality was present in 27 and no abnormality in 21. All patients underwent coronary angiography. The sensitivity of adenosine echocardiography for greater than or equal to 75% coronary artery diameter stenosis was 85% (46 of 54), with a specificity of 92% in patients with normal coronary arteries. In the 35 patients with a normal baseline electrocardiogram the sensitivity was 60%; 9 (82%) of 11 patients with multivessel disease were correctly identified. The sensitivity for adenosine electrocardiography (greater than or equal to 1-mm ST depression) was 35% with a specificity of 100%. Side effects were transient and mild; aminophylline was used in two patients. Thus, ischemic changes can be induced in patients with coronary artery disease with intravenous adenosine that, combined with echocardiography, is sensitive for the assessment of ischemic heart disease, particularly in patients with multivessel disease. PMID- 1918703 TI - Effect of infarct size measured from antimyosin single-photon emission computed tomographic scans on left ventricular remodeling. AB - To evaluate the effect of infarct size on left ventricular volumes and geometric remodeling, 26 patients with a first acute Q wave myocardial infarction (anterior in 14, inferior in 12) had the infarct sized from single-photon emission computed tomographic (SPECT) imaging of indium-111 antimyosin. All patients underwent gated blood pool scintigraphy before hospital discharge for determination of ejection fraction and end-diastolic and end-systolic volume indexes. Infarct size was quantitated from indium-111 antimyosin uptake in coronal slices with use of a threshold technique for edge detection. Nineteen of 26 patients had additional simultaneous acquisitions of indium-111 and thallium-201 uptake and the infarct was expressed as a percent of the total left ventricle. Infarct size was larger (59 +/- 16 vs. 33 +/- 16 g), predischarge ejection fraction lower (35 +/- 5% vs. 60 +/- 9%) and end-systolic volume index higher (57 +/- 13 vs. 36 +/- 10 ml/m2) in the group with anterior infarction. Despite these differences, predischarge end-diastolic volume index was not significantly different between the group with anterior (88 +/- 17 ml/m2) versus inferior (89 +/- 14 ml/m2) infarction. There was a significant inverse correlation between percent infarct size and ejection fraction for patients with dual isotope imaging (r = -0.90) and a significant direct correlation between infarct size and end-systolic volume index (r = 0.79, p less than 0.01). Fourteen patients without subsequent myocardial infarction or coronary artery bypass grafting had a repeat gated blood pool study late (26 +/- 15 months) after infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918706 TI - Refractory ventricular fibrillation in the electrophysiology laboratory: a nightmare from which we can awaken. PMID- 1918705 TI - Emergency intracardiac defibrillation for refractory ventricular fibrillation during routine electrophysiologic study. AB - Ventricular fibrillation refractory to cardiopulmonary resuscitation including multiple transthoracic defibrillations occurred in four patients during 1,215 consecutive ventricular tachycardia induction studies. A technique of emergency intracardiac defibrillation for management of refractory ventricular fibrillation is described. In four patients, stable monomorphic ventricular tachycardia (320 to 570 ms cycle length) was induced during the study and overdrive ventricular pacing resulted in ventricular fibrillation. These patients did not respond to prompt transthoracic defibrillations (5 to 15 attempts/patient) and cardiopulmonary resuscitation, including antiarrhythmic therapy. As a last resort, intracardiac defibrillation was performed with use of a previously inserted standard right ventricular quadripolar catheter as cathode and a posterior skin patch as anode. High energy intracardiac defibrillation pulses (100 to 500 J) delivered from a standard defibrillator successfully terminated each arrhythmia. Intracardiac defibrillation is technically simple and appears effective in terminating refractory ventricular fibrillation in the electrophysiology laboratory. However, further research is necessary to determine the safety and efficacy of this technique, as well as potential applications in other emergency settings. PMID- 1918707 TI - Transcatheter closure of a large patent ductus arteriosus with the clamshell septal umbrella. AB - In 14 patients undergoing transcatheter closure of a large (greater than 4 mm diameter) patent ductus arteriosus, occlusion was attempted with use of the Bard Clamshell septal umbrella. Patient age ranged from 0.7 to 30.4 years. Isolated patent ductus arteriosus was present in 11 patients; 3 had additional congenital heart lesions. Moderate or severe pulmonary hypertension was present in four patients. The diameter of the patent ductus arteriosus ranged from 4.5 to 14 mm, as determined by contrast injection through an 11F sheath or by balloon sizing; it appeared larger by this method than by the standard angiographic method. All 14 patent ductus arteriosi were successfully closed. Prior embolization of a Rashkind umbrella was the reason for using a Clamshell device in three patients; one additional embolization of a Clamshell device occurred. All errant devices were retrieved at cardiac catheterization, without associated hemodynamic instability. No other complications occurred. Among the 14 patients, 11 had complete ductal closure by Doppler color flow mapping at last follow-up and 3 had trivial residual flow. All four patients having associated complex lesions or pulmonary hypertension, or both, had symptomatic improvement after the procedure, although one child (with Shone's anomaly) died 3 months later. The Clamshell device provides stable and effective closure of a large patent ductus arteriosus, and allows transcatheter closure to be offered to some patients who were previously considered unsuitable for this procedure. PMID- 1918708 TI - Percutaneous implantation of a balloon-expandable endoprosthesis for pulmonary artery stenosis: an experimental study. AB - Conventional therapy to treat peripheral pulmonary artery stenosis (surgery or balloon angioplasty) has been frustrating. Recently a variety of peripheral vascular stenoses, in which conventional approaches are disappointing, have become amenable to therapy with the use of a balloon-expandable endovascular stent. This experimental study was designed to assess the application of such a prosthesis in artificially created pulmonary artery stenoses. In 9 of 12 2-week old pigs, left pulmonary artery stenosis was surgically created (3.9 +/- 1.1 mm diameter and 7 +/- 1 mm Hg mean gradient). At 6.8 +/- 1 weeks of age (13 +/- 4 kg), percutaneous (femoral venous) implantation of a 3-cm long balloon-expandable (maximal diameter 18 mm) stent (three placed into normal pulmonary artery branches) using a 3-cm x 10-mm balloon dilating catheter was achieved without technical difficulties. Stenoses were enlarged to 8.3 +/- 1.4 mm with a decrease in mean gradient to 1 +/- 1 mm Hg that was maintained through 3.5 months of follow-up. Histologic and electron micrographic studies identified normal appearing neoendothelial layering over stent struts without intraluminal or peripheral thrombus formation and nonobstructed side branching to lung subsegments. These findings support the application of this approach in the treatment of pulmonary stenosis that is not amenable to conventional therapy. PMID- 1918709 TI - Balloon valvuloplasty versus closed commissurotomy for pliable mitral stenosis: a prospective hemodynamic study. AB - Closed surgical mitral valvotomy is the procedure of choice in most patients with symptomatic pliable mitral stenosis in developing countries. The procedure is efficacious and safe. Mitral valvotomy performed with a balloon has shown similar good results, with infrequent complications in selected subjects. Because there is a paucity of studies comparing the two techniques, this study was undertaken to compare the results of percutaneous balloon mitral valvuloplasty with those of closed commissurotomy as determined by catheterization studies. Forty-five patients with tight pliable mitral stenosis were randomly assigned to one of two groups: 23 patients had balloon valvuloplasty by the single catheter technique (group I) and 22 underwent closed surgical valvotomy (group II). The two groups were similar with regard to clinical and hemodynamic findings before intervention. Mitral valve area increased from 0.8 +/- 0.3 to 2.1 +/- 0.7 cm2 in group I (p less than 0.001) and from 0.7 +/- 0.2 to 1.3 +/- 0.3 cm2 in group II (p less than 0.001). Pulmonary artery pressure and pulmonary vascular resistance decreased in both groups, but these changes did not reach statistical significance in group II. Treadmill exercise time increased from 3.8 +/- 2.3 to 7.3 +/- 2.6 min in group I (p less than 0.001) and from 4 +/- 2.6 to 5.6 +/- 2.6 min in group II (p less than 0.001). There were no deaths. One patient in each group developed moderate (3+) mitral regurgitation. A small interatrial shunt (less than 1.5:1) was detected in three patients in group I immediately after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918710 TI - High dose titration of calcium channel blocking agents for primary pulmonary hypertension: guidelines for short-term drug testing. AB - Forty-seven patients with primary pulmonary hypertension were evaluated with a dose titration protocol utilizing nifedipine (20 mg orally) or diltiazem (60 mg orally) given every hour until maximal effectiveness was achieved. Of the patients tested, 15 (32%) had a greater than 20% reduction in pulmonary artery pressure (mean 36.2 +/- 8%, p less than 0.01) and pulmonary vascular resistance (mean 50.2 +/- 7%, p less than 0.01) (pressure responders). Nineteen (40%) had a greater than 20% reduction in pulmonary vascular resistance (mean 25.2 +/- 12%, p less than 0.01), with less than a 20% decrease in pulmonary artery pressure (resistance responders). Ten had no significant change in pulmonary artery pressure or pulmonary vascular resistance (nonresponders), and three were unable to tolerate the calcium channel blocking agents. No hemodynamic profile allowed prediction of the type of response to these agents. No mortality or serious morbidity was associated with the drug testing. These findings indicate that calcium channel blockers, when titrated to maximally effective doses, may cause substantial reductions in pulmonary artery pressure and pulmonary vascular resistance in patients with primary pulmonary hypertension. Testing with hemodynamic monitoring is necessary to ascertain which patients will respond. Patients with primary pulmonary hypertension are able to tolerate short-term administration of high doses of calcium channel blockers. PMID- 1918711 TI - Testicular dysfunction with amiodarone use. AB - Amiodarone, an antiarrhythmic drug approved for use in patients who survive cardiac arrest, has been associated with infiltration of or inflammatory changes in various tissues. To date thyroid dysfunction has been the only endocrine disturbance noted. In an initial group of seven amiodarone-treated men undergoing evaluation for sexual dysfunction, an elevation in serum gonadotropin concentration was detected, suggesting testicular dysfunction. Because of this finding, gonadal function was prospectively evaluated in 44 men (18 who had been treated with amiodarone for greater than 1 year and 26 survivors of cardiac arrest who had been treated with antiarrhythmic drugs other than amiodarone). Amiodarone-treated men had higher serum follicle-stimulating hormone (41.8 +/- 22.8 vs. 14.4 +/- 10.4 mIU/ml, p less than 0.001) and luteinizing hormone (34.8 +/- 26.4 vs. 10.1 +/- 5.2 mIU/ml, p less than 0.001) concentrations compared with control subjects. Although serum total and free testosterone levels were comparable between the two patient groups, these levels were inversely correlated (r = -0.53, p less than 0.05; r = -0.62, p less than 0.01, respectively) with cumulative amiodarone dose. Hyperresponsiveness to the administration of gonadotropin-releasing hormone was noted in the 10 amiodarone-treated men evaluated by this diagnostic test. Sexual dysfunction was common in both groups (70% of control subjects and 82% of amiodarone-treated subjects), although atrophic testes were more commonly observed in amiodarone-treated men (p less than 0.05). Because of the elevated serum gonadotropin level, it is concluded that testicular dysfunction may result from prolonged amiodarone treatment. PMID- 1918712 TI - Transesophageal echocardiography: procedures and clinical application. AB - In existence for more than a decade, transesophageal echocardiography has gained renewed interest because of technologic advances including high resolution transducers, multiple imaging planes and Doppler color flow mapping. The heart is imaged from within the esophagus with a gastroscope-mounted transducer, obviating technical difficulties encountered in transthoracic echocardiography. Transesophageal echocardiography is utilized intraoperatively to monitor patients undergoing open heart surgery or high risk cardiac patients undergoing noncardiac surgery. In the ambulatory patient, the procedure facilitates imaging of many structures (including the left atrium and appendage, mitral and aortic native and prosthetic valves and thoracic aorta), with better resolution than that obtained by routine transthoracic echocardiography. Technical aspects of transesophageal echocardiography as well as its indications and limitations are reviewed. PMID- 1918713 TI - Antitachycardia devices: realities and promises. AB - Nonpharmacologic therapy for ventricular arrhythmias has gained growing attention with the development of the implantable cardioverter-defibrillator. In addition, the reports of adverse effects of drug therapy from several studies, including the Cardiac Arrhythmia Suppression Trial (CAST), have supported the need for these devices. The development of new implantable cardioverter-defibrillators that have the capability of antitachycardia pacing, bradycardia pacing, cardioversion and defibrillation has enhanced their clinical utility. The currently available implantable cardioverter-defibrillators have been shown to significantly improve survival after sudden cardiac arrest in patients with life threatening ventricular arrhythmias. Newer devices with expanded capabilities may reduce mortality even further. In this report the features of currently available antitachycardia devices and implantable cardioverter-defibrillators are reviewed and the features and current implant data on newer antitachycardia devices are discussed. PMID- 1918714 TI - Pseudo 2:1 atrioventricular block and T wave alternans in the long QT syndromes. AB - The extreme prolongation of ventricular action potential duration that occurs in some of the long QT syndromes may result in two forms of alternating activity of the heart: a "pseudo" 2:1 atrioventricular (AV) block and a T wave alternation, both of which are rate dependent. The pseudo 2:1 AV block relates to the extreme prolongation of ventricular refractoriness. The T wave alternation reflects the fact that the rate dependence of action potential duration differs in degree or magnitude in the subendocardial and subepicardial layers of the ventricular wall. Examples of two cases previously reported in the Journal by Weintraub et al. are used to illustrate and discuss these manifestations. PMID- 1918715 TI - Cardiac abnormalities in the toxic oil syndrome, with comparative observations on the eosinophilia-myalgia syndrome. AB - Early in the course of studies of the Spanish toxic oil syndrome it was recognized that vascular lesions were a major problem, most logically attributable to endothelial damage by the toxic oil. However, most clinical attention has been directed to the pulmonary complications and the evolution into a scleroderma-like illness later. In this study of 11 victims of the toxic oil syndrome careful postmortem studies of the coronary arteries and conduction system and neural structures of the heart demonstrated major injury to all those components of the heart. Obliterative fibrosis of the sinus node in four cases resembled findings in fatal scleroderma heart disease, and in eight the cardiac lesions resembled those of lupus erythematosus. The more impressive pathologic features involved the coronary arteries and neural structures, which were abnormal in every heart. The arterial disease included widespread focal fibromuscular dysplasia, but there was also an unusual myointimal proliferative degeneration of both small and large coronary arteries in five patients, four of whom were young women. In two hearts, portions of the inner wall of the sinus node artery had actually detached and embolized downstream. Coronary arteritis was rarely found. Inflammatory and noninflammatory degeneration of cardiac nerves was widespread. Fatty infiltration, fibrosis and degeneration were present in the coronary chemoreceptor. In most respects these cardiac abnormalities resemble those described in the eosinophilia-myalgia syndrome caused by an altered form of L-tryptophan. In both diseases there is good reason to anticipate more clinical cardiac difficulties than have so far been reported, and even more basis for future concern, especially relative to coronary disease and cardiac electrical instability. PMID- 1918716 TI - Quantitation of the extent of acute myocardial infarction by phosphorus-31 nuclear magnetic resonance spectroscopy. AB - Phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy is able to identify alterations in myocardial high energy phosphate metabolism associated with acute infarction. It was hypothesized that the extent of acute myocardial infarction could be quantitated from changes in the tissue content of inorganic phosphate (Pi), phosphocreatine (PCr) and adenosine triphosphate (ATP) derived from P-31 NMR spectra. Nine isolated, perfused rat hearts were studied at 121.5 MHz. After baseline spectra were obtained, varying locations of either the right or the left coronary artery were occluded without removing the heart from the spectrometer. Spectra were then collected during regional ischemia at 15 and 45 min after occlusion. Phosphate metabolites were quantitated from the baseline and 45-min regional ischemia spectra, times at which the metabolites are at steady state for the normal and ischemic conditions. The heart was removed from the spectrometer, perfused for a total duration of 2 h and sectioned into 2-mm thick slices for triphenyltetrazolium chloride staining. Percent infarct was determined by manual tracing of magnified, digitized images of the stained sections. Coronary blood flow, heart rate and blood pressure were monitored throughout the experiment. Significant linear relations were found between percent infarct (by triphenyltetrazolium chloride staining) and the percent change of beta-ATP (r = 0.74), Pi (r = 0.83) and the PCr/Pi ratio (r = -0.71) at 45 min after coronary occlusion. Coronary flow was also found to correlate significantly with percent infarct (r = -0.70). These results are applicable to in vivo P-31 NMR studies of acute infarction where the volume of interest may include both normal and acutely infarcted myocardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918717 TI - Reciprocal strains in the normal and ischemic myocardium and their relation to the size of the ischemic region. AB - Previous studies have reported "bulging" of the ischemic zone and reciprocal shortening of the normal zone during the isovolumetric contraction period. This study examines the interaction and relation of these reciprocal strains during the isovolumetric contraction period. Normal zone and ischemic zone segment length data were acquired at 1 ms intervals during acute ischemia in 10 open chest dogs. The relation of ischemic zone and normal zone segment length was inversely linear in the isovolumetric contraction period during steady state ischemia and during preload reduction (mean correlation coefficient 0.92). The slope derived from the regression analysis was the same as that determined from the first and last data points of the isovolumetric contraction period (correlation coefficient between the regression versus two-point slope 0.96). This slope was used to calculate the size of the ischemic area based on the hypothesis that the isovolumetric normal zone shortening quantitatively accounted for the ischemic zone bulging during the isovolumetric contraction period, with the percent risk region serving as a weighing factor. The calculated risk region correlated with the anatomic risk region (r = 0.83, p less than 0.01; n = 9) and was independent of preload. During the isovolumetric contraction period, left ventricular short-axis diameter shortened approximately 0.2%; 80% of the ischemic zone lengthening occurred during this period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918718 TI - Dynamics of coronary occlusion in the pathogenesis of myocardial infarction. AB - In most coronary artery stenoses in humans, lumen size decreases in response to acute vasoconstriction, reduced aortic pressure or passive collapse. Because the effects of vasoconstriction and plaque rupture with thrombus formation are additive, in some cases total cessation of flow may result from only minimal obstruction by thrombus. This hypothesis was investigated with use of a previously developed model of the coronary circulation in which the pressure drop across and flow through an arterial stenosis were determined by standard hemodynamic equations. The vessel wall was assumed to be composed of pliable and rigid sections, as is the case in most arterial stenoses in humans. The computer analysis was conducted for a rigid stenosis and for a dynamic stenosis in which proximal artery constriction and distal collapse were simulated. Plaque rupture with subsequent thrombus formation was simulated as a decrease in lumen area without effect on the arterial wall. Compared with a dynamic stenosis, a rigid stenosis required a significantly larger thrombus for vessel occlusion. Thrombus formation equal to the nonobstructed area of the lumen was required to occlude a rigid vessel; a 60% stenotic vessel required a 40% plaque rupture with thrombus formation for occlusion. However, for a dynamic stenosis, if vasoconstriction and passive collapse were simulated, small plaque ruptures led to vessel occlusion: a 60% stenotic vessel required only a 12% plaque rupture with thrombus formation for occlusion. This analysis indicates that even mild coronary lesions may be responsible for myocardial infarction, suggesting that vasomotion may be a very important element in the pathogenesis of most myocardial infarcts. PMID- 1918719 TI - Arrhythmias induced by device antitachycardia therapy due to diagnostic nonspecificity. AB - New technology has produced automatic cardioverter-defibrillators capable of delivering antitachycardia pacing, as well as low and high energy shocks and backup bradycardia pacing. These expanded treatment options have led to a wider range of clinical applications for such devices, including the treatment of ventricular tachycardias with longer cycle lengths, which may overlap the cycle lengths of some supraventricular arrhythmias. The diagnostic capability of these devices, although improved, has not advanced sufficiently to ensure reliable discrimination between all supraventricular and ventricular arrhythmias. Two cases are presented in which device-mediated pacing therapy, triggered by supraventricular arrhythmias, induced ventricular tachycardia requiring additional therapeutic intervention. This report illustrates the therapeutic versatility and some of the potential pitfalls, of the recently developed devices and reviews the status of automatic arrhythmia identification technology. PMID- 1918720 TI - The health policy retreat. PMID- 1918721 TI - Molecular biology and immunology: an introduction. PMID- 1918722 TI - Maternal smoking does not influence cord serum IgE or IgD concentrations. AB - Increased cord blood IgE concentrations have been related to atopic risk in children, and a previous study reported increased cord blood IgE concentrations in smoking mothers. These associations suggest a relationship between maternal smoking during pregnancy and atopic risk. To evaluate this question, we prospectively studied parental smoking and cord blood IgE and IgD concentrations in a geographically defined group of women belonging to a health maintenance organization. Cord blood samples were obtained from 847 infants born to these women. Cotinine concentrations were measured in 114 cord blood samples to evaluate the veracity of the maternal smoking histories. Smoking during the prenatal period was reported by 144 mothers (17%) and 204 fathers (25%). Decreased birth weight and length were associated with maternal smoking (p less than 0.001 for both), confirming previous studies. Neither maternal nor paternal smoking was found to be associated with IgE level in univariate or multivariate analyses. Maternal and paternal smoking was associated with IgD (p = 0.03 and p = 0.06, respectively) in univariate analysis. In multiple regression analysis controlling for potentially confounding variables, the association between paternal, but not maternal, smoking and IgD was sustained (p = 0.05 and p greater than 0.20, respectively). Our data do not demonstrate that maternal or paternal smoking increases cord blood IgE. PMID- 1918723 TI - Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. AB - The late asthmatic reaction (LAR), consecutive to bronchial allergen challenge, is characterized both by the influx of various cells in proximal and distal airways and by the enhancement of bronchial hyperresponsiveness. However, the exact conditions for the development of the inflammatory reaction during the LAR remain to be specified. Since monokines play a key role in inflammatory processes, particularly in the lung, the production of tumor necrosis factor alpha (TNF-alpha), interleukin; 1-beta (IL-1-beta) and interleukin-6 (IL-6) by alveolar macrophages (AM), collected 18 to 20 hours after exposure to allergen, was evaluated in 15 allergic subjects with asthma submitted to a challenge test with Dermatophagoides pteronyssinus (N = 6) or with wheat flour (N = 9) and in three healthy subjects. After bronchial provocation test, four patients presented no bronchial response (group 1), and six patients, a single early reaction (group 2). In contrast, five patients developed successively an immediate plus a late response (group 3). The monokine production was compared to that from nine allergic subjects with asthma studied at baseline (group 0) and from 11 unchallenged healthy subjects (control subjects). Measurements of cytokines were evaluated for TNF-alpha and IL-1-beta by a specific immunoradiometric assay, whereas IL-6 levels were appreciated by the proliferation of 7TD1 cells. No detectable amounts of TNF-alpha, IL-1-beta, and IL-6 were in bronchial alveolar lavage fluid, even after a tenfold concentration. In contrast, a significant increase of TNF-alpha (10,642 +/- 3127 U/ml) and IL-6 (1250 +/- 427 U/ml) concentrations was noted in AM supernatants from patients exhibiting an LAR (group 3) compared to cells recovered from groups 2, 1, and 0 and to challenged or unchallenged control subjects (805 +/- 244, 995 +/- 521, 1269 +/- 524, 688 +/- 85, and 445 +/- 74 pg of TNF-alpha per milliliter, respectively; 190 +/- 64, 114 +/- 91, 242 +/- 95, 80 +/- 9, and 54 +/- 19 U/ml of IL-6 per milliliter, respectively). No modification of IL-1-beta contents could be detected between the different groups. A significant correlation was detected between concentrations of TNF and IL-6 (r = 0.92; p less than 0.001). These results demonstrate TNF-alpha and IL-6 secretion by AM consecutively to the development of LAR in allergic subjects with asthma, confirming that AMs are activated after allergen challenge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1918724 TI - Effects of dose and dosing schedule of inhaled budesonide on bone turnover. AB - To assess whether the use of larger than usual doses of inhaled steroid to treat severe asthma may adversely affect bone turnover and whether such an effect may be mitigated by altering the dose schedule, we investigated the effects of budesonide (BUD) on serum osteocalcin and the urinary output of hydroxyproline and calcium. Healthy adults were administered 1.2 or 2.4 mg of BUD per day (N = 40) or placebo (N = 8) in a crossover, double-blind comparison of morning versus diurnal dosing schedules for 1 month each. Both BUD doses reduced the 24-hour urinary free-cortisol output (p less than 0.001) and serum osteocalcin (p less than 0.001). The larger dose reduced the morning serum cortisol levels (p = 0.002). Neither dose increased the 8 AM urinary calcium or hydroxyproline output. Osteocalcin and plasma cortisol levels were higher on morning than on diurnal dosing (p = 0.01). The 24-hour urinary free-cortisol output was the same with either schedule (p = 0.96). Additional study is required to assess the clinical importance of the inhibitory effect of BUD on bone formation, as evidenced by the reduction in osteocalcin levels. Of concern is the possibility of serious bone complications resulting from the long-term use of inhaled steroid, particularly in growing children or patients in whom other risk factors for osteoporosis are present. The clinical advantage, if any, of morning dosing remains questionable. PMID- 1918725 TI - Prevalence of specific IgE to the storage mite, Aleuroglyphus ovatus. AB - Aleuroglyphus ovatus (Ao) is a storage mite that has a worldwide distribution and has been found in stored bran, wheat, chicken meal, and dried fish products. Ao was isolated from a chicken meal sample, cultured on whole wheat flour at 75% relative humidity, and 1 gm of pure Ao bodies were extracted, 1:20 wt/vol, in 0.2 mol/L of ammonium bicarbonate. Der p I, major allergen of Dermatophagoides, pteronyssinus (Dp), or Der f I major allergen to Dermatophagoides farinae (Df), was not detected in extracts of Ao. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed 25 bands (6 to 110 kd), and thin-layer isoelectric focusing revealed 19 bands (isoelectric point, 3.5 to 9.3). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots with six different sera identified nine IgE binding bands (16 to 100 kd). Thin-layer isoelectric focusing immunoblots identified 16 IgE binding bands (isoelectric point, 4.5 to 9.3). An aliquot of the Ao extract was diluted in bicarbonate buffer (pH 9.2) and adsorbed to plastic microtiter plates. RAST to Ao and Dp were performed with sera of 163 atopic individuals (88 with allergic rhinitis and 75 with allergic asthma with or without allergic rhinitis). All individuals had appropriately positive skin tests that correlated with a history of exacerbation secondary to allergen exposure. RAST results to Dp and Ao were analyzed by regression analysis (r = 0.64; p = 0.0001). Fifty-five individuals were RAST positive to Dp alone, 32 to Ao and Dp, and three to Ao alone; 73 individuals were negative to Ao and Dp. RAST inhibition demonstrated moderate cross-reactivity between Ao and Dp. PMID- 1918727 TI - Immunoglobulin concentrations in nasal secretions differ between patients with an IgE-mediated rhinopathy and a non-IgE-mediated rhinopathy. AB - Nasal secretions from patients with an IgE-mediated rhinopathy, patients with a non-IgE-mediated rhinopathy, and healthy control subjects were collected with a newly developed direct aspiration system. Total protein, albumin, secretory IgA (sIgA), IgE, IgG, and IgM concentrations were measured in the nasal secretions to detect whether the nasal pathology is reflected in nasal secretion protein concentrations. It was found that protein and immunoglobulin concentrations in nasal secretions were inversely related to amount of secretion in the nasal cavity. Both patients' groups had a significantly higher sIgA to protein ratio than the healthy control subjects. Furthermore, patients with an IgE-mediated rhinopathy had significantly higher sIgA and IgM to total protein ratios in their nasal secretions than patients with a non-IgE-mediated rhinopathy. Probably these differences are due to changes in immunoregulation. PMID- 1918726 TI - Antagonism of airway reactivity induced by ovalbumin antigen in guinea pigs by 5 amino-4-imidazolecarboxamide riboside. AB - The effect of 5-amino-4-imidazolecarboxamide riboside (AICA riboside), a modulator of purine metabolism, was studied on antigen-induced bronchospasm in ovalbumin (OA)-sensitized guinea pigs. In separate experiments, sodium cromoglycate (SCG) and terbutaline were used to compare their effectiveness with that of AICA riboside (wt/vol). AICA riboside and SCG were administered as an aerosol daily for a minimum of 2 weeks before OA aerosol challenge. Terbutaline, as an aerosol, was administered once 5 minutes before OA challenge. Airway reactivity was determined through the use of a whole-body plethysmography by monitoring specific airway resistance (SRaw). OA aerosol challenge of 0.05%, 0.1%, and 0.25% (wt/vol), administered for a period of 1 minute, increased SRaw. Each of the three agents attenuated the effect of OA on SRaw, although terbutaline demonstrated more consistency and potency as compared to either AICA riboside or SCG. However, at moderate degrees of OA challenge, AICA riboside appeared to be as effective as either agent. Although the mechanism of action of AICA riboside remains uncertain, it may have therapeutic benefit in the treatment of asthma or allergic diseases. PMID- 1918728 TI - Topical thrombin-induced IgE-mediated anaphylaxis: RAST analysis and skin test studies. AB - Bovine topical thrombin (BTT) is a heterologous plasma thrombin concentrate that has been frequently used for the hemostasis since the 1940s. Recently, three patients in Japan went into shock after the topical application of BTT at lesion sites, and two of these patients had received BTT repeatedly. The clinical symptoms and the increased anti-BTT percent RAST counts suggest that these reactions were shock mediated by anti-BTT IgE antibodies. The RAST-inhibition analysis suggested that the antigenic substance(s) were bovine-specific moiety(ies) mainly involved in the contaminant rather than bovine thrombin itself. The skin tests were studied to predict such allergic reactions. The intracutaneous test provoked nonspecific reactions even at the low concentrations of BTT. The prospective study on the predictive value of the prick test with 1000 U/ml (1 mg/ml) of BTT in 192 patients suggested that it is useful to detect highly sensitive patients. In addition, the increased levels of anti-BTT IgE antibodies in patients 1 month after the single administration of BTT suggested the immunogenicity of the topical application of BTT. PMID- 1918729 TI - Episodic eosinophilia-myalgia-like syndrome in a patient without L-tryptophan use: association with eosinophil activation and increased serum levels of granulocyte-macrophage colony-stimulating factor. AB - We have studied a patient with recurrent bouts of angioedema, myalgia, and eosinophilia that was not due to L-tryptophan ingestion. Peripheral blood eosinophils (EOSs) during exacerbations of his illness displayed characteristics of "activation," including hypodense phenotype and increased responsiveness to platelet-activating factor (PAF) in vitro with respect to expression of CD11b surface adhesion proteins. Elevated serum levels of granulocyte-macrophage colony stimulating factor (GM-CSF) bioactivity were also detected, whereas interleukin-3 and interleukin-5 levels were not increased. During treatment with glucocorticoids, all clinical symptoms resolved, EOSs decreased in number and became normodense, PAF responsiveness diminished, and GM-CSF levels returned to normal. During glucocorticoid tapering, a subsequent clinical relapse was again associated with EOS hypodensity, increased PAF responsiveness, and increased serum GM-CSF levels. Although this patient satisfies the diagnostic criteria for eosinophilia-myalgia syndrome, the episodic and profound nature of exacerbations and response to therapy in the absence of L-tryptophan usage suggests a possible overlap with the syndrome of episodic angioedema and eosinophilia. In vitro studies suggest that GM-CSF may play a role in the eosinophilia, EOS activation, and pathophysiology of disease in this patient and demonstrate resolution of these abnormalities during glucocorticoid therapy. The efficacy of glucocorticoid therapy in some hypereosinophilic states may therefore be mediated, at least in part, via reduction of GM-CSF production and/or EOS activation. PMID- 1918730 TI - Indirect evidence of bronchial inflammation assessed by titration of inflammatory mediators in BAL fluid of patients with asthma. AB - Bronchial inflammation is a characteristic of asthma that may be examined indirectly by bronchoalveolar lavage (BAL). Nine normal individuals were compared with 38 age-matched adults with asthma of variable severity to appreciate the importance of cell activation in the severity of asthma. The severity of asthma was appreciated by the clinical score of Aas and the pulmonary function of the patients. FEV1 ranged between 35% and 130% of predicted. The indirect activation of eosinophils (EOSs), mast cells, fibroblasts, and neutrophils was examined by the titration of eosinophil cationic protein (ECP), tryptase, hyaluronan (HA), and myeloperoxidase (MPO) by radioimmunoassay in BAL fluid (BALF) and cytology of BALF. In the adults with asthma, there was a significantly increased number of EOSs and a significantly increased level of all mediators but MPO. MPO levels were increased in seven patients only; three of these patients were previous smokers. Only ECP and HA levels were significantly correlated with the severity of asthma. These results demonstrate EOSs, mast cells, and fibroblasts are activated in asthma, whereas the involvement of neutrophils is less clear. There was a significant correlation between ECP and HA levels, suggesting a common activation of EOSs and fibroblasts. PMID- 1918731 TI - Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness. AB - Bronchial biopsy specimens were obtained by fiberoptic bronchoscopy from 21 atopic subjects with asthma, 10 atopic subjects without asthma, and 12 normal healthy control subjects. With immunohistochemical techniques and a panel of monoclonal antibodies, inflammatory cells were identified and counted in the bronchial mucosa. The mean number of leukocytes (CD45+) and T-lymphocytes (CD3+, CD4+, and CD8+) at two airway levels in the subjects with asthma tended to be higher than in the other groups, but this difference did not achieve statistical significance. Similarly, there were no significant differences in the numbers of mucosal-type or connective tissue-type mast cells, elastase-positive neutrophils, or Leu-M3+ cells in the airway mucosa of subjects with asthma compared with atopic subjects without asthma and healthy control subjects. In contrast, significantly more interleukin-2 receptor-positive (CD25+) cells and "activated" (EG2+) eosinophils (EOSs) were present in the airways of subjects with asthma at both proximal and subsegmental biopsy sites. When the relationships between numbers of T-lymphocytes, activated (CD25+) cells, and EOSs were analyzed, there were positive correlations between CD3 and EG2, between CD3 and CD25, and between CD25 and EG2 positive cells in the airways of subjects with asthma. Furthermore, the ratio of EG2+ to CD45+ cells correlated with the provocative concentration of methacholine that caused a 20% decrease of FEV1 in hyperresponsive subjects. Although these associations do not prove a causal relationship, the results support the hypothesis that activated (CD25) T-lymphocytes release products which regulate recruitment of EOSs into the airway wall. In addition, our findings suggest that, in the large airways at least, asthma is not associated with hyperplasia of either mucosal-type or connective tissue-type mast cell. PMID- 1918732 TI - Sinusitis: a critical need for further study. PMID- 1918733 TI - Comparison between Der p I plus Der f I content determinations and guanine measurements in 239 house dust samples. PMID- 1918734 TI - Urticaria from caffeine. PMID- 1918735 TI - Regional expression of cold urticaria. PMID- 1918737 TI - Further comments on the environment. PMID- 1918736 TI - Vitamin E and HIV infection. PMID- 1918738 TI - Role of consultant dietitians in nursing homes. PMID- 1918739 TI - New food products aid management of renal insufficiency. PMID- 1918740 TI - Factors influencing success of dietitians employed in business and industry. AB - Career opportunities in business and industry have been identified as one area of growth for the dietetics profession. The purposes of this study were to identify the skills, attributes, and knowledge areas dietitians need to succeed in business and industry; ascertain methods used to acquire these; assess factors that influenced career change; and determine the degree of perceived adequacy of academic preparation by practitioners employed in business and industry. A questionnaire, developed on the basis of a Delphi study involving 21 dietitians employed in business and industry, was administered to a national sample of 387 members of the Dietitians in Business and Industry (DIBI) dietetic practice group who were employed in business and industry. The overall response rate was 299 (77%); respondents were from 39 states. Skills, attributes, and knowledge areas were identified for specific employment classifications in business and industry. Self-motivation and work experience in business were identified as the most important methods for acquiring skills for this area of practice. Challenge of a new position and diversity of job responsibilities had the most influence on career change of respondents. Undergraduate and graduate education were rated somewhat inadequate and adequate, respectively, by the majority of respondents. The findings indicate that positions in business and industry require specific skills, attributes, and knowledge that may not necessarily be attained through traditional approaches. Self-assessment and appropriate self-development activities are essential for success. PMID- 1918741 TI - Dietary management of malnourished children with a new enteral feeding. AB - Balance (nitrogen, fat, carbohydrate) and growth studies were carried out in nine children (6 to 26 months old) recovering from protein-energy malnutrition (PEM) using a concentrated (1 kcal/mL) formula designed specifically for 1- to 6-year olds. The formula provided 12% of energy as protein (18% whey, 82% casein), 44% of energy as carbohydrate (69% corn syrup solids, 31% sucrose), and 44% of energy as fat (50% high-oleic safflower oil, 30% soy oil, 20% medium-chain triglycerides). Means +/- standard deviations of apparent nitrogen retention and absorption were 90 +/- 3% and 39 +/- 13%, respectively. Mean fecal fat excretion was 1.3 +/- 1.0 g/day. Length-age increased 3.0 +/- 0.8 months and weight-age increased 8.3 +/- 3.8 months during the 2.4 +/- 0.3 months of the study. (Length age and weight-age were defined as the age (in months) to which the child's length or weight corresponded at the 50th percentile of the National Center for Health Statistics reference data). Thirteen additional 40- to 30-month-old children with kwashiorkor were fed the formula for 8 to 35 days as part of the initial management of PEM. The result was prompt weight gain and increases in serum proteins. Its formulation and the findings of our study indicate that this new formula offers a notable advantage over products designed for infants or adults in the enteral alimentation of young children. PMID- 1918742 TI - Status of training programs and perceived labor problems in four types of noncommercial foodservice operations. AB - Training is essential for the effective delivery of quality foodservice products. A well-developed training program is ongoing, comprehensive, planned in advance, and performance based. Such programs facilitate performance and may be beneficial to develop employees and reduce employee turnover rates. The purpose of this study was to investigate the kinds of training programs that are being developed and delivered to employees in noncommercial foodservice operations. A survey instrument was mailed nationally to foodservice directors and administrators in health care and educational foodservice operations requesting information about training programs used for their nonsupervisory foodservice employees. Information regarding perceived existence of potential labor problems was also collected. Relationships between training programs and perception of labor problems were investigated. Training appears to be conducted in some form within the four types of noncommercial foodservice operations investigated. The most severely perceived labor problems among nonsupervisory employees include low motivation, lack of skills, and poor promotability. PMID- 1918743 TI - Why treatments for obesity don't last. AB - Behavioral self-management training is the state of the art in the treatment of obesity. However, most of those treated experience only temporary success in keeping weight off. In some individuals, relapse appears to be related to the development of binge eating, which is characterized by perceived lack of eating control and symptoms of food dependence. Treatment for such patients should be based on the assumptions that self-management is very difficult and that emphasis should be on cognitive-behavioral methods with a reliance on social support for control of behavior. For some patients, continued use of the self-management model may result in harmful weight cycling. PMID- 1918744 TI - Obesity treatment: the high cost of false hope. AB - Although millions seek treatments for obesity, the benefits of treatment have been overstated. For most people, treatment is not effective; the majority of the obese struggle in vain to lose weight and blame themselves for relapses. Repeated experiences of failure add to the psychologic burden caused by the social stigma and the presumption of psychopathologic conditions attached to obesity. Many therapists may be contributing to this psychologic damage by giving their patients false hope for success and by failing to recognize that seeking treatment for obesity may be triggered by psychologic problems that are not addressed in obesity treatment. PMID- 1918745 TI - Weight loss programs: failing to meet ethical standards? AB - Ethical concerns raised by the treatment of obesity include the following: the question of whether obesity treatment is accurately described as therapy or as research given its low percentage of long-term success; the need for standardized disclosure of the possibility of harms vs the low probability of benefits; the status of voluntary and informed consent as a meaningful model of patient cooperation in treatment in light of reported findings of "treatment addiction" as a recognized syndrome; and the policy issues raised by the absence of uniform standards for and regulatory oversight of weight loss programs. PMID- 1918746 TI - Government should strengthen regulation in the weight loss industry. AB - Rationales for government regulation in the weight loss industry are developed on the basis of the concepts of market failure and potential harm to consumers. Evidence shows that consumers face problems in judging the quality of the industry's products and services, and they lack adequate protection against possible harm. The pros and cons of a variety of public and private strategies are examined for correcting these deficiencies. Recommendations are suggested for strengthening existing government regulations and expanding research. PMID- 1918748 TI - Using thresholds to monitor dietetic services: the JCAHO 10-step process for quality assurance. AB - The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) is the licensing and governing agency for the evaluation of health care services. The JCAHO has developed a 10-step process to assist health care organizations in establishing appropriate quality assurance programs. The 10-step process guides the practitioner through problem identification, monitoring, evaluation, reporting, and problem resolution. Dietitians at 20 hospitals ranging in size from 125 to 1,538 beds were surveyed to obtain threshold designations used to monitor 19 dietetic services indicators in their quality assurance program. A threshold, usually designated as a percentage, corresponds to a numeric measurement. For example, a threshold of 90% would indicate that one unacceptable finding in 10 findings would meet the threshold designation for a particular indicator. The survey designated five threshold ranges--100%, 99%-90%, 89%-80%, 79%-70%, and 69%-50%--as well as the responses "no threshold set" and "not monitoring." A cumulative analysis of responses revealed that use of the five threshold ranges was reported with the following frequency: 100% threshold--16% (60 of 380) of responses; 99%-90% threshold--40% (154 of 380) of responses; 89% 80% threshold--6% (21 of 380) of responses; 79%-70% threshold--2% (7 of 380) of responses; 69%-50% threshold--1% (6 of 380) of responses; and no threshold or not monitoring--35% (132 of 380). PMID- 1918747 TI - Ethics of obesity treatment: implications for dietitians. AB - Dietitians face both a responsibility and an opportunity to address the ethical issues of obesity treatment and to promote weight management strategies that are beneficial and effective. The Code of Ethics for the Profession of Dietetics, which was adopted in 1989 to provide guidance to dietetics practitioners in their professional practice and conduct, can serve as a guide in an evaluation of current obesity treatments. Dietitians must help clients be realistic about their weight loss goals and address emotional conflicts that may be undermining weight management efforts. Referrals to therapists may be indicated, and dietitians must be prepared to recognize the need and make the recommendations. Dietitians should take the lead in developing more ethical and beneficial treatments by collaborating with government and industry to protect the consumer from ineffective or potentially harmful practices. PMID- 1918749 TI - Effect of diet on progression of chronic renal disease. AB - Changes in renal function induced by protein intake are thought to reflect evolutionary adaptation of the kidney. Excess dietary proteins over long periods may increase normal blood flow and glomerular filtration rate, requiring the continuous use of outer cortex's reserve glomeruli. According to the hyperfiltration theory, pressures and flows in outer cortical glomeruli contribute to continuous intrarenal capillary hypertension and predispose healthy people to progressive glomerular sclerosis and deterioration of renal function. Pressures and flows associated with the response to renal disease in turn may accelerate the development of sclerosis, leading to even more rapid loss of renal function. Restriction of dietary protein (less than or equal to 0.6 g/kg per day) and/or phosphorus seems to slow the rate of loss of renal function in patients with chronic renal insufficiency. Evidence for the role of lipids in the progression of renal disease is not clear. All of these dietary factors possibly play a role in the progression of renal disease; the relative importance of each factor varies, depending on the pathogenesis, stage, and mechanism of progression of the disease. Findings indicate that nutrition therapy can decrease rate of deterioration of renal function in patients with chronic renal diseases. PMID- 1918751 TI - Dietary quality and concerns about body weight of low-income pregnant women. PMID- 1918750 TI - Treating malnutrition in AIDS: comparison of dietitians' practices and nutrition care guidelines. AB - The acquired immunodeficiency syndrome (AIDS) is a complex disease; its manifestations include many opportunistic infections that lead to conditions causing severe malnutrition. Overcoming malnutrition can help AIDS patients increase their weight, improve their self-image, and enhance the quality of their lives. Thirty-eight dietitians who work with AIDS patients in New York City were surveyed to determine whether their facilities followed 40 suggested guidelines for the assessment and treatment of malnutrition in AIDS. Thirty dietitians (80%) reported that their facilities followed more than half of the suggested guidelines. Many guidelines were "always" followed by a majority of facilities. Those not followed might provide a focus for dialogue among practitioners with regard to nutrition care procedures. Thirty-two (84%) dietitians reported receiving AIDS education, including in-service programs (n = 18), professional meetings (n = 27), and formal education (n = 3). AIDS education in both undergraduate and graduate curriculums and additional continuing education programs are needed. Persons with AIDS are at high risk for nutrition-related disorders. Practitioners need to know and apply nutrition care guidelines suggested in the literature to improve the quality of care for this growing population. PMID- 1918752 TI - Estimating stature from knee height for persons with cerebral palsy: an evaluation of estimation equations. PMID- 1918753 TI - Position of the American Dietetic Association: fat replacements. PMID- 1918754 TI - Carolyn McCorkindale wins Huddleson Award. PMID- 1918755 TI - Bringing ADA's strategic plan to life: choice, caring, compassion, collaboration, and compensation. PMID- 1918756 TI - Relationship of family communication patterns to eating disorder inventory scores in adolescent girls. AB - This study attempted to identify risk factors for the development of the psychological and behavior traits associated with eating disorders. Subjects were 454 healthy, high school girls; their responses to the Eating Disorder Inventory (EDI) were correlated with information obtained through a personal-background questionnaire. Students who perceived their guardians as persons who always lectured them about their problems or discounted the importance of their problems scored significantly higher on the eight EDI subscales than did respondents who reported other perceptions. Students who perceived their guardians as unwilling to listen to their problems tended to score higher on all the EDI subscales; significant differences were found between the scores of those responding "always" and "never"/"rarely" willing to listen. Students who responded that they were always uncomfortable discussing problems with their guardians tended to have a higher mean score on all but the Drive for Thinness and Body Dissatisfaction subscales. The empirical data on the family interaction patterns support the theory that certain family relationships contribute to the development of the psychological and behavior traits assessed by the EDI. PMID- 1918757 TI - Relationship of self-concept to nutrient intake and eating patterns in young women. AB - The relationships between attitudes toward oneself (self-concept) and nutrition related behavior were examined for 153 single women aged 18 to 35 years. Nutrition-related behaviors were assessed with 3-day food records that were analyzed for nutrient composition and eating patterns (Basic Four Food Group scores, number of meals per day, and percent of energy from meals and snacks). Attitudes toward self, knowledge and attitudes about nutrition, and general health practices were assessed with a written questionnaire that incorporated several existing scales. Because of potential overlap among the three self concept scales, as well as nutrition-attitude and health-practice items, responses were factor analyzed, yielding 14 factors. These factors were then compared with nutrient intake and eating patterns. Scores for the seemingly desirable factors of the "Super Person" or "Do Your Own Thing" were negatively correlated with intake of several nutrients; scores on the self-perception of a "Traditional" orientation to life were positively related to calcium intake and meal patterns. The "Nutrition Is Important" and "Nutrition Knowledge" factors were also positively related to desirable eating patterns and nutrient intakes. We conclude that several self-concept variables, as well as nutrition attitudes and knowledge, can potentially influence nutrient intakes and eating patterns in young women. PMID- 1918758 TI - Physicians' perceptions of the role of clinical dietitians are changing. AB - We surveyed a selected group of physicians to determine their opinions regarding appropriate activities and educational background for hospital dietitians. Questionnaires were mailed to 401 physicians listed in the yellow pages of the 1988 San Jose/Santa Clara, Calif, telephone directory. Physicians were chosen from nutrition-related specialties such as cardiology, endocrinology, and gastroenterology. Questionnaires were returned by 123 (30%) physicians. Most physicians viewed dietitians as contributing members of the health care team. However, they believed that the physician should be responsible for ordering therapeutic diets. Most physicians (98%) agreed that one of the most important duties of the dietitian is to assure patient satisfaction with food served. Physicians (94%) also believed that presenting current nutrition information to hospital personnel is an important activity. Counseling patients was an area most physicians (99%) thought should be included in the educational background of dietitians. Sixty percent of the physicians indicated that it is important for the dietitian to understand blood and urine laboratory values. These results indicate that the perceived status of hospital dietitians by physicians has improved since earlier studies. PMID- 1918759 TI - Nutrition information needs during cardiac rehabilitation: perceptions of the cardiac patient and spouse. AB - A survey instrument, which was developed from personal interviews with participants in a cardiac rehabilitation program, was administered at two hospital-based Phase II cardiac rehabilitation programs. Thirty-five patients (28 men, 7 women) and 29 spouses (5 men, 24 women) responded to survey items designed to investigate how subjects perceived themselves dealing with the cardiac diet, what questions they were asking, and how answers to those questions would help them. Subjects in the patient group (which was 80% male) most frequently asked questions dealing with compliance and the diet's benefits. Subjects in the spouse group (which was 83% female) most frequently asked questions relating to food selection. Participants indicated that having their questions answered would help them make decisions, be motivated, feel in control, and plan. Participants' overall attitude toward the diet was positive because patients were willing to make changes in their diet; however, more than half the sample thought food labels were difficult to understand and grocery shopping was difficult. We conclude that nutrition education programs that address individual needs and uses for nutrition information could enhance the learning process in group settings such as cardiac rehabilitation programs. PMID- 1918760 TI - Infant feeding practices of migrant farm laborers in northern Colorado. AB - The purpose of this study was to provide descriptive information on migrant farm laborers' infant feeding practices in northern Colorado. We used a survey questionnaire to interview 49 families with a 6- to 23-month-old child who was enrolled in the Migrant Head Start Center. Sixteen (33%) of the mothers breast fed their infants, but only five (14%) of the 35 Mexican Americans breast-fed. Thirty-four (69%) of the mothers used formula and seven (14%) gave their child cow's milk at birth. Introduction of solids occurred at a mean of 6.6 months. Of the respondents, 13 (27%) introduced solids before 4 months of age, whereas 29 (59%) introduced solids before the age of 6 months. Thirty-six (73%) of the migrants put their child to bed with a sweetened beverage, milk, or formula in a bottle. Diarrhea in the children was reported by 39 (80%) of the migrants, with 15 (31%) stating that it occurred at least once per month. One third (n = 16) of the respondents reported that their children had constipation lasting 1 to 14 days, but for most (n = 10) it occurred less than once per month. Results suggest that migrant families need more dietary recommendations about breast-feeding, introduction of liquids/solid foods, proper formula preparation, avoidance of baby bottle tooth decay, and treatment of diarrhea and constipation. PMID- 1918761 TI - Total factor productivity modeling in hospital foodservice operations. AB - Total factor productivity (TFP) modeling, a ratio of outputs to inputs, was elaborated with terminology, resources, and outputs familiar to foodservice managers and evaluated for four hospital foodservice operations. Outputs and inputs (counts or currency) were converted to constant dollars for a defined base period by using base period rates and price indexes. After development, validation and pilot testing of a computer-assisted prototype, monthly TFP ratios were calculated from historical data. When TFP ratios were analyzed by regression against each of nine variables (six work force policies, two "demand for services" variables, and capital investment), few significant relationships were found. Although multiple regression analysis of those variables did not produce useful predictive equations, a similar analysis of partial and total factor productivity ratios yielded predictive equations that included up to four partial factor productivity ratios. Even though the labor statistic of meals per labor hour correlated positively with TFP ratios, the comparison provided incomplete and sometimes contradictory information. Total factor productivity measurement can provide foodservice managers with a more comprehensive analytical technique than is possible with only partial measures of productivity. PMID- 1918762 TI - Weight reduction interventions for persons with a chronic illness: findings and factors for consideration. AB - Obesity in persons with a concomitant chronic illness poses complex issues relating to the choice of appropriate interventions. More recent emphasis on modification of risk factors has resulted in the need to prescribe complex therapeutic regimens with multiple treatment goals. The traditional approach to weight reduction in such persons has been nutrition education. Studies have shown, however, that knowledge alone does not translate into self-care behaviors that in turn result in weight loss and weight maintenance. Although the latter outcomes continue to be primary goals of therapy in obese individuals with a chronic illness, improvement in the physiologic parameters associated with the illness is also a desired outcome. Behavior therapy and group support appear to be enabling factors that go beyond knowledge to facilitate behavior change and subsequent changes in health-related indexes. This article describes various approaches to the problem of combined interventions for patients education and weight reduction. Findings and factors are discussed about whether the primary goal of weight reduction interventions for persons with a chronic illness should focus on pounds lost or improvement in metabolic or physiologic status. PMID- 1918763 TI - Immediate and sustained reduction in serum cholesterol achieved in 4-week Heart Tune program. AB - Currently, there is limited information about educational models effective in assisting individuals to lower their serum cholesterol. Dietitians and nutritionists involved in cholesterol-reduction programs need to inform other health professionals about programs utilized and the success of those programs. The National Cholesterol Education Program has published guidelines for the detection, evaluation, and treatment of high blood cholesterol in adults. Educational programs should be systematically evaluated to confirm their success in cholesterol reduction. The Heart Tune program is a 4-week class developed by a dietitian to assist clients in cholesterol reduction. An evaluation of the lipoprotein levels of 49 program participants demonstrated that serum total cholesterol levels significantly decreased at the completion of the 4-week class (0.65 mmol/L) and after 1 year (0.80 mmol/L). PMID- 1918764 TI - The CARDIA dietary history: development, implementation, and evaluation. AB - To meet the objectives for dietary assessment in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective study, we developed a dietary history to provide accurate and reliable quantitative data on habitual individual nutrient intakes at baseline. The CARDIA dietary history was an interviewer administered method that included a short questionnaire regarding general dietary practices followed by a comprehensive food frequency questionnaire about typical intake of foods using the previous month as a reference for recall. For each broad category of foods, participants were questioned in detail about specific foods only if they indicated that they consumed foods from that category. Follow up questions for selected foods concerned serving size, frequency of consumption, and common additions to these foods. Provision was made for reporting foods not found in the food frequency list. The interview took approximately 45 minutes. Cue cards prompted responses and plastic food models assisted in estimating usual amounts consumed. A precoded format standardized coding for reported items and established the detail needed for recall during the interview. Baseline nutrient analyses from the CARDIA dietary history provided estimates that agreed reasonably well with expected caloric intake for body mass index according to the age- and sex-specific Recommended Dietary Allowances, but were higher than those reported from 24-hour recalls for comparable age, sex, and race groups in the second National Health and Nutrition Examination Survey. The CARDIA dietary history is a comprehensive assessment tool that can provide a dietitian with detailed information regarding habitual eating patterns and nutrient intakes among adults. PMID- 1918765 TI - A family focus program to lower blood cholesterol. PMID- 1918766 TI - Dietary fat: sources of information used by men. PMID- 1918767 TI - Nutrient intakes of women who use oral contraceptives. PMID- 1918768 TI - Taste alterations in bone marrow transplant patients. PMID- 1918769 TI - Position of the American Dietetic Association: competitive foods in schools. PMID- 1918770 TI - Caring and sharing. The American Dietetic Association, 74th annual meeting. October 28-31, 1991, Dallas, Texas. Abstracts. PMID- 1918772 TI - Left bundle branch block developing in a patient with sub-therapeutic nortriptyline levels: a case report. PMID- 1918771 TI - Thyroid stimulating hormone elevation without antithyroid antibody elevation in nursing home patients. AB - OBJECTIVES: To investigate the relationship between antithyroid antibody elevation and thyrotropin (TSH) elevation. SETTING: Large state veterans home. METHODS: Seven hundred seventy-six residents were screened for TSH elevation. Seventy-two residents with TSH elevation and no history of thyroid disease or recent iodine exposure later had determinations of antithyroglobulin and antimicrosomal antibodies. The relationship between TSH levels and antibody titers was explored. RESULTS: Eleven percent of the residents had TSH elevation. Thirty-two percent of men and 64% of women with TSH elevation had elevation of antithyroid antibodies. Those residents with the highest antithyroid antibody titers had significantly greater TSH elevation. CONCLUSION: Previous investigators have found similar percentages of individuals with TSH elevation who lack antithyroid antibody elevation. We hypothesize that TSH elevation without elevated antibody titers may be the result of a previously described involutional histologic lesion of the thyroid. PMID- 1918773 TI - Prevalence and consequences of vitamin deficiency in the nursing home: a critical review. PMID- 1918774 TI - Beyond Cruzan: individual rights, family autonomy and the persistent vegetative state. PMID- 1918775 TI - Cerebrospinal fluid markers of Alzheimer's disease. AB - OBJECTIVE: To review studies on cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD) in order to answer the question whether CSF contains a specific marker which can be used to support a clinical diagnosis of AD. DATA SOURCES: Studies identified through an English-language literature search using MEDLINE (1966 to 1990) and a review of bibliographies of relevant articles. STUDY SELECTION: All studies on CSF in AD patients were selected. Double publications on the same original data were not included. Otherwise, no particular selection was made. DATA EXTRACTION: The diagnostic utility of more than 60 substances, including CSF measures related to classical neurotransmitters, (neuro)peptides, proteins, amino acids, purines, trace elements, and constituents of senile plaques and neurofibrillary tangles, is evaluated. Clinical epidemiological criteria for deciding on the usefulness of new diagnostic methods are emphasized in this analysis. DATA SYNTHESIS: Concentrations of some CSF constituents are consistently found to be significantly changed in AD. However, overlap with data of control populations and methodological shortcomings in study design, limit the diagnostic value of all CSF measurements reviewed. CONCLUSIONS: None of the CSF constituents studied so far can be used in support of the diagnosis of AD. However, increased knowledge concerning macromolecular abnormalities in amyloid containing plaques and neurofibrillary tangles makes the outlook for a diagnostic test for AD on CSF promising. PMID- 1918777 TI - Sterile vs clean urinary catheterization. PMID- 1918776 TI - Treatment of nursing home-acquired pneumonia. PMID- 1918778 TI - Acute pancreatitis in the elderly. PMID- 1918779 TI - Subcutaneous infusions in the elderly. PMID- 1918780 TI - Early readmission of elderly patients with congestive heart failure. PMID- 1918781 TI - The picture sign in dementia. PMID- 1918782 TI - Daytime sleepiness in the healthy "old old": a comparison with young adults. AB - OBJECTIVE: To determine if excessive daytime sleepiness is an inevitable consequence of aging. METHODS: Daytime sleepiness was measured using Multiple Sleep Latency Tests (MSLT's) before and after a night of total sleep deprivation in a sample of 22 healthy men and women in their eighties and 29 men and women in their twenties. RESULTS: Young adults were somewhat sleepier than elders, as measured by rapidity of sleep onset during daytime nap recordings using the MSLT, and showed a higher incidence of REM sleep during naps. However, recovery from the effects of acute sleep loss was slower in the elderly, judging from the presence of more daytime sleepiness 2 days after a night of total sleep deprivation. Such persistent sleepiness was absent in the young adult control group. CONCLUSIONS: Healthy persons in late old age may have a level of daytime sleepiness no greater than, and perhaps even less than, that seen in healthy young adults. PMID- 1918783 TI - Incidence and characteristics of antibiotic use in aged nursing home patients. AB - OBJECTIVE: To measure the prevalence, incidence, types, and certain characteristics of antibiotics prescribed in nursing homes. DESIGN AND SETTING: Periodic survey over 1 year of patient charts in 53 stratified, randomly selected nursing homes in the state of Maryland. PATIENTS: All patients 65 years of age or more residing in these nursing homes on the first day of study. RESULTS: Of 4,165 patients in 53 nursing homes, records over the year were satisfactory in 3,899 patients in 52 nursing homes. The prevalence of antibiotic use on the first day of the study was 8%. Over the next 12 months, observations of more than one million patient-days revealed an incidence of 0.46 antibiotic courses/100 patient days; 54% of the 3,899 patients received at least one antibiotic course. For presumed active infections, beta lactam antibiotics were the most commonly used, 54% of antibiotic orders. For all antibiotics, urinary tract infection was the most common indication, eliciting 36% of orders including 9% for asymptomatic bacteriuria. Skin, lower respiratory, and upper respiratory infections comprised 14%-17% each. Physicians prescribed 94% of courses but documented examinations of only 44% of patients at the outset of these courses. Consensus criteria for minimal diagnostic evaluation of four selected infections were met in only 11% of episodes of infection. Although the most serious infections tended to be better evaluated than others, 31% of the former were not noted to have been examined by a physician. Three percent of orders were for prophylaxis and two-thirds of these antibiotics were administered for more than 2 days. CONCLUSIONS: Antibiotics are frequently prescribed for aged nursing home patients, often in the absence of a physician's examination and other features commonly performed in evaluation of specific infectious diseases. More than one-fifth of antibiotics prescribed by presumed active infections were for two infections usually thought not to require antibiotic therapy, "viral" upper respiratory infection (13%) and asymptomatic bacteriuria (9%). To optimize antibiotic use in nursing homes, greater attention should be directed to appropriate durations of prophylaxis for urologic, dental, and minor surgical procedures; to standards for diagnostic evaluations of common infections; and to the roles of antibiotics in upper respiratory infections and in asymptomatic bacteriuria. PMID- 1918784 TI - Low Body Mass Index in demented outpatients. AB - In order to determine the association between dementia and low body weight in outpatients, Body Mass Index (BMI) was evaluated prospectively in 346 frail elderly outpatients presenting for comprehensive geriatric assessment. Patients were categorized into four groups (cognitively intact, dementia of the Alzheimer's type (DAT), other dementia, and patients with depressive symptoms). Patients were assessed for severity of dementia by the Clinical Dementia Rating scale. Differences between groups for various clinical parameters were evaluated using an analysis of variance and Duncan's Multiple Range Test. Patients with dementia, regardless of etiologic type or severity, and patients with depressive symptoms had BMI's greater than or equal to 10% lower than the cognitively intact patients. BMI was positively correlated with Instrumental Activities of Daily Living (IADL) but not Activities of Daily Living (ADL) or Mini-Mental State Exam (MMSE) score. Low BMI was not associated with increased physical illness. In fact, in the subset of patients with DAT, lower BMI correlated with significantly lesser amounts of comorbid physical illness. Finally, compared to cognitively intact outpatients, patients with DAT appeared to be physically healthier despite their having a lower BMI. These results suggest an association between dementia and low BMI. On the other hand, the presence of comorbid physical illness, a common focus of evaluation in these patients, was not more common in those patients with lower BMI's. PMID- 1918786 TI - Two-year trends in physical performance following supervised exercise among community-dwelling older veterans. AB - The extent to which exercise can delay the normal decline in physical performance associated with aging is unknown. We examined the impact of 2 years of supervised exercise on cardiovascular fitness, flexibility, and strength in a group of elderly (age 65-74) veterans. Seventy-five patients exercised 3 days/week for 90 minute sessions emphasizing aerobic, flexibility, and strength development. Thirty-six (47%) completed 2 years of a voluntary supervised exercise program (n = 16-25 with complete data). Over a 2-year follow-up period, cardiovascular outcome variables improved significantly: metabolic equivalents increased 20% (7.4 +/- 2.2 to 9.0 +/- 2.4, P less than 0.001) and submaximal heart rate decreased 7% (131.4 +/- 14.8 to 121.0 +/- 18.5 beats/minute, P = 0.06). Resting heart rate decreased 8% (68.5 +/- 8.0 to 63.6 +/- 8.4 beats/minute, P = 0.02) but this difference did not reach statistical significance. Flexibility, measured by hamstring length, improved 11% (57.5 +/- 15.1 to 64.0 +/- 11.1 degrees, P = 0.02). Strength variables did not improve. The study indicates that improvements in cardiovascular function and flexibility achieved by the elderly in the early stages of an exercise program can be maintained for at least 2 years. PMID- 1918785 TI - A randomized study of ciprofloxacin versus ceftriaxone in the treatment of nursing home-acquired lower respiratory tract infections. AB - OBJECTIVE: To compare the efficacy and safety of ciprofloxacin and ceftriaxone in patients with nursing home-acquired lower respiratory tract infections requiring initial hospitalization. DESIGN: Prospective, randomized trial. SETTING: Extended care nursing homes affiliated with a teaching hospital. PATIENTS: Fifty patients aged 60 years or older with normal or mildly impaired renal function admitted to the hospital for treatment of lower respiratory tract infections. INTERVENTIONS: Twenty-four patients received initial therapy with intravenous ciprofloxacin, 200 mg every 12 hours (19 patients) or 400 mg every 12 hours (5 patients) during the acute phase followed by 750 mg orally every 12 hours during the convalescence phase. Twenty-six patients received initial therapy with intravenous ceftriaxone, 2 g every 24 hours during the acute phase followed by 1 g administered intramuscularly every 24 hours during the convalescent phase. The total duration of therapy was 14 days. MAIN OUTCOME MEASUREMENTS: Successful outcome was defined as resolution or marked improvement in clinical signs and symptoms of lower respiratory tract infection upon completion of the treatment course. RESULTS: Twelve (50%) of the ciprofloxacin-treated and 14 (54%) of ceftriaxone-treated patients had successful outcomes. Recurrent oropharyngeal aspiration was the reason for treatment failure in most patients refractory to either antibiotic. Mortality during therapy was 8% in each group. From 21 satisfactory sputum specimens collected, S. pneumoniae was the most common isolate, followed by H. influenzae and other Gram-negative bacteria. Ciprofloxacin therapy was well tolerated; ceftriaxone therapy was discontinued in two patients (8%) due to adverse reactions (intramuscular pain and drug fever). CONCLUSIONS: Sequential intravenous/oral ciprofloxacin appears to be as safe and effective as sequential intravenous/intramuscular ceftriaxone. The optimal dosage of intravenous ciprofloxacin in this patient population appears to be 400 mg every 12 hours; however, additional clinical and pharmacokinetic studies with this regimen are warranted. PMID- 1918787 TI - Dipyridamole echocardiography as a useful and safe test in the assessment of coronary artery disease in the elderly. AB - We prospectively studied the sensitivity, specificity, feasibility, and safety of high-dose dipyridamole echocardiography, compared to exercise electrocardiography in 130 subjects (67 younger and 63 elderly patients) referred for angiographic evaluation of suspected or proven coronary artery disease. Sensitivity, specificity, and feasibility of dipyridamole echocardiography were respectively 75.5%, 100%, and 88.0% in younger patients and 82.9%, 100%, and 79.4% in elderly patients (P = NS). The sensitivity of exercise electrocardiography was 72.7% in young and 66.6% in elderly patients (P = NS); specificity 66.0% vs 60.0% (P = NS); feasibility 83.6 vs 63.5 (P = 0.05). Forty-nine younger and 38 elderly patients performed both tests. Sensitivity of dipyridamole echocardiography compared to exercise electrocardiography was 76.2% vs 73.8% in young patients and 83.3% vs 70% in the older group (P = NS). The feasibility of the two tests was significantly different in the elderly group only (dipyridamole echocardiography 79.4% vs exercise electrocardiography 63.5%; P less than 0.01). The incidence of side effects during dipyridamole echocardiography was similar in the two groups, except for dyspnea which was observed in 20% of older and 5% of younger patients (P less than 0.05). Our data demonstrate that the dipyridamole test combined with echocardiographic monitoring of regional myocardial contractility may be considered a valid non-invasive method for evaluating coronary artery disease in the elderly and that this test is a satisfactory alternative to the exercise stress test. PMID- 1918788 TI - Inhalation toxicity of methyl isocyanate: biochemical and cytological profile of bronchoalveolar lavage fluid in rats. AB - Acute pulmonary injury in rats following a single inhalation exposure to methyl isocyanate (3.2 mg l-1) was reflected by alterations in the biochemical and cytological constituents of bronchoalveolar lavage fluid (BALF) over a period of 30 days. Total protein, sialic acid and lactic acid contents of BALF were increased followed by a gradual decline to normalcy between day 3 and day 30 post exposure. The activity of lactic dehydrogenase also increased progressively with time. The cellularity of BALF was increased significantly and primarily comprised of polymorphonuclear neutrophils at 8 days. The adherence of macrophages was unchanged but their viability was lowered at 30 days post-exposure. The results indicate the significance of bronchoalveolar lavage analysis in monitoring pulmonary toxicity by methyl isocyanate, which is characterized by the hypoxic condition and reduced cellular defence. Some toxic manifestations are potentially reversible with time after cessation of exposure. PMID- 1918790 TI - Chinese hamster ovary cell assays for mutation and chromosome damage: data from non-carcinogens. AB - In vitro genotoxicity tests are employed to screen chemicals for their capability to cause various DNA and chromosomal alterations, and the results are often used to predict their potential for carcinogenicity. However, there is controversy regarding the apparent low specificity of some in vitro genotoxicity assays, which result in a high false positive rate. Since we use and rely upon in vitro assays for risk assessment and prediction of carcinogenicity, this specificity issue is of serious concern to us. Hence, we selected ten compounds deemed non carcinogens in the literature to test for the induction of gene mutation and chromosomal damage using the Chinese hamster ovary cell/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) mutation assay performed concurrently with a CHO micronucleus assay. The chemical exposures for the two end-points were done simultaneously. The protocol for the two end-points was developed using the carcinogens N-methyl-N'-nitro-N-nitrosoguanidine, 3-methylcholanthrene, cyclophosphamide and 7,12-dimethylbenzanthracene. The non-carcinogens chosen were 4-nitro-o-phenylenediamine, p-phenylenediamine dihydrochloride, 3-nitropropionic acid, dichlorvos, 2-(chloromethyl)pyridine, N-(1-naphthyl)ethylenediamine 2HCl, O anthranilic acid, 4-nitroanthranilic acid, anilazine and triphenyltin hydroxide. Each of these chemicals had been reported positive in the Ames test and/or the mouse lymphoma TK+/- mutation assay. In addition, eight of them were also reported positive in in vitro assays for chromosome aberrations and/or sister chromatid exchange (SCE). We found four of the ten chemicals negative for gene mutation and micronucleus induction without and with activation in the CHO/HGPRT mutation and CHO micronucleus assays. However, one of these four chemicals may be a potential carcinogen according to other carcinogenicity reviewers. Four other chemicals that induced only micronuclei were negative for gene mutation. Dichlorvos was positive for gene mutation and micronucleus induction without and with activation. This chemical has been shown recently to cause various tumors in rodents. One of the non-carcinogens was positive in the micronucleus test and equivocally positive in the mutation test. These results indicate that the CHO/HGPRT mutation assay may provide more relevant results than the CHO micronucleus assay, the mouse lymphoma mutation assay, or in vitro SCE and chromosome aberration assays when screening chemicals for potential carcinogenicity. PMID- 1918789 TI - Assessment of cadmium-induced osteopenia by measurement of serum bone Gla protein, parathyroid hormone, and 1 alpha,25-dihydroxyvitamin D. AB - To assess the osteopenia induced by environmental cadmium (Cd) exposure by measurement of serum bone Gla protein (BGP), parathyroid hormone (PTH) and 1 alpha,25-dihydroxyvitamin D (1 alpha,25(OH)2D), 29 men and 41 women who lived in a Cd-polluted area and showed renal tubular dysfunction were selected. To evaluate the degree of osteopenia, microdensitometry (MD) was used. Compared with the non-exposed subjects, the levels of serum creatinine and BGP, urinary Cd and beta 2-microglobulin and blood Cd were higher, while the levels of serum inorganic phosphorus and MD indicators were lower in the Cd-exposed group. In simple correlation matrix, BGP showed significant correlations with serum alkaline phosphatase (S-Al-p) and MD indicators in the Cd-exposed men, and also correlations with S-Al-p and 1 alpha-25(OH)2D in the Cd-exposed women. Applying multivariate analysis to the Cd-exposed subjects, BGP, %TRP and base excess were found to show significant associations with the MD indicators in the men. In the women, PTH, age, blood Cd and BGP were associated significantly with the MD indicators. Only serum BGP showed a significant correlation in both sexes of the Cd-exposed subjects, and a sex difference was found in the relationship between bone metabolic markers and osteopenia. These results suggest that serum BGP has a close independent association with the osteopenia induced by Cd exposure and that BGP, which has a different biological function from that of PTH or 1 alpha,25(OH)2D, may be a useful indicator to detect bone damage in Cd-exposed subjects. PMID- 1918791 TI - Cardiopathic effect of 1,2,3-trichloropropane after subacute and subchronic exposure in rats. AB - 1,2,3-Trichloropropane (1,2,3-TCP) is an industrial water contaminant with potential for human exposure by the oral route. The systemic toxicology of 1,2,3 TCP was evaluated after subacute or subchronic exposure in male and female Sprague-Dawley rats. Animals were treated with 0.01, 0.05, 0.20 and 0.80 mmol kg 1 day-1 for 10 days and 0.01, 0.05, 0.10 and 0.40 mmol kg-1 day-1 for 90 days. Chemical exposure was by oral gavage in corn oil. Lethality did not occur in either study. Toxicity was observed primarily in the high dose group of subacute and subchronically treated rats of both sexes. Weight gain suppression occurred at a dose of 0.8 mmol kg-1 (118 mg kg-1) after 10 days. After 90 days of exposure to 0.40 mmol kg-1, the final body weights were 81% and 86% of control values for males and females, respectively. When major organ weights were normalized by body weight, liver and kidney values were generally increased relative to control in the two highest dose groups after 10- and 90-day chemical exposure. Serum chemistries and histopathology indicated a mild hepatotoxic response to 1,2,3-TCP in the high dose group of each study but did not support any renal toxicity. Thymic weight reduction due to atrophy occurred at 10 days of exposure in high dose groups but was normal in all groups after the 90-day treatment. The primary histological finding in this study was an inflammation-associated cardiopathy produced by 1,2,3-TCP. Myocardial necrosis and degeneration occurred in a diffuse pattern with marked eosinophilia of affected cells. Male and female animals showed a cardiopathic response only at a dose of 0.8 mmol kg-1 1,2,3-TCP after the 10-day exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918792 TI - Trichloroethylene interactions with muscle cells. AB - The toxic effect of trichlorethylene (TCE) was investigated on isolated muscles prepared from frog and rats. Twitch and tetanic contractions as well as caffeine induced contractures, were recorded. Trichloroethylene at a concentration of 0.25 4.0 mM depressed the force development of both twitch and tetanic tension in a dose-dependent manner. This effect was not influenced by the type of muscle. As TCE shortened the time to peak of twitch contractions, it may alter the Ca2+ binding kinetics. Subthreshold caffeine concentrations applied after pre-exposure to TCE (1 or 2mM) induced contractures. The same TCE exposure enhanced regular caffeine contractures through increasing the speed of tension development and the absolute force. Exposure to 5 or 10 mM TCE did not affect the first caffeine induced contracture but enhanced the potency of the second caffeine dose given 15 min after the first. The results suggest that the interaction of TCE with membrane sites is responsible for Ca2+ release for contractile processes. PMID- 1918793 TI - Effectiveness of some chelating agents on distribution and excretion of vanadium in rats after prolonged oral administration. AB - Vanadium has been shown to have a number of insulin-like effects and has been demonstrated to be beneficial in the treatment of streptozotocin-diabetic rats when included in the drinking water. However, some signs of toxicity and vanadium accumulation in all analysed tissues were reported in vanadium-treated animals. In the present study, the effect of repeated intraperitoneal administration of sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron), ascorbic acid and deferoxamine mesylate (DFOA) or 2-mercaptosuccinic acid on the distribution and excretion of vanadium was determined in male Sprague-Dawley rats. Rats received sodium metavanadate (NaVO3) or vanadyl sulphate pentahydrate (VOSO4.5H2O) in the drinking water at concentrations of 0.15 mg ml-1 (NaVO3) and 0.31 mg ml-1 (VOSO4.5H2O) for 6 weeks. After the end of this exposure period, chelating agents were administered for 2 weeks (3 days per week) at doses approximately equal to one-tenth of their respective LD50. Urine was collected on days 1, 7 and 14 of treatment. Twenty-four hours after the final chelator injection, rats were killed and vanadium concentrations were determined in various tissues. Tiron and DFOA were effective compounds in mobilizing vanadium after NaVO3 administration, whereas Tiron was the most effective chelator after vanadyl sulphate administration. Ascorbic acid neither increased urinary elimination nor decreased tissue vanadium concentrations. PMID- 1918794 TI - Site of action of grayanotoxins in mad honey in rats. AB - Grayanotoxins are known to occur in honey produced from the nectar of Rhododendrons of the family Ericaceae. Grayanotoxins extracted from honey sample obtained from a patient who experienced severe bradycardia and hypotension after ingesting two tablespoonfuls corresponded to Rhododendron ponticum tetrades. Anaesthetized albino rats were injected with honey extract intracerebroventricularly or intraperitoneally. The intracerebroventricular dose was equivalent to 50 mg honey and i.p. doses were equivalent to 50 mg, 1 mg kg-1 and 5 g kg-1 honey. Marked bradycardia and respiratory rate depression were observed in rats injected with extract equivalent to 1 and 5 g kg-1 honey i.p. and in rats injected with 50 mg i.c.v., but not in rats given 50 mg i.p. In bilaterally vagotomized animals, grayanotoxin-contaminated honey extract was not bradycardic. These results suggest that the sites of cardiac and respiratory actions are within the central nervous system, and that the bradycardic effect of grayanotoxin is mediated by vagal stimulation at the periphery. PMID- 1918795 TI - Biochemical toxicology of argemone oil. I. Effect on hepatic cytochrome P-450 and xenobiotic metabolizing enzymes. AB - The in vivo effect of argemone oil on hepatic xenobiotic metabolizing enzymes was investigated in albino rats following either a single (10 ml kg-1 body wt.) or multiple intraparenteral doses (5 ml kg-1 body wt.) for three days. Animals sacrificed 72 h after a single intraparenteral dose of argemone oil exhibited a significant loss of hepatic cytochrome P-450 (35%) and cytochrome b5 (34%) contents and inhibition of aminopyrine-N-demethylase (APD), aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin-O-deethylase (ECD) activities (21-39%). Three successive 24-hourly intraparenteral injections of argemone oil followed by sacrificing the animals after 24 h of the last injection, showed a greater degree of inhibition of the content of cytochrome P-450 (58%) and its dependent mixed function oxidases (35-63%). Also, multiple treatment of argemone oil caused a depletion of endogenous hepatic glutathione (GSH) content (72%) with a concomitant increase in lipid peroxidation (177%) and decrease in glutathione-S transferase (GST) activity (30%). A significant decrease in relative liver weight (39%) was observed in animals treated with multiple treatment of argemone oil. These results suggest that argemone oil can alter both membrane and cytosolic defences and destabilizes the hepatic cytochrome P-450 dependent mixed-function oxidase system, so that it tips in the direction of autooxidative peroxidation of lipids. PMID- 1918796 TI - Early decreases in pulmonary, hepatic and renal glutathione levels in response to cadmium instillation into rat trachea. AB - After instillation of cadmium (Cd) into the rat trachea, reduced and oxidized glutathione (GSH and GSSG) levels in the lung, liver and kidney were studied in relation to Cd concentrations and metallothionein (Mt) contents. Rats instilled with Cd developed haemorrhagic pneumonia, which deteriorated with a marked swelling of the lung throughout the experimental period of 48 h. The total glutathione (GSH + GSSG) level in the organs decreased after 6 h to 60-70% of the control levels. The decreased glutathione level was never restored to the control level within 48 h in the lung, and was possibly due to the pneumonia. Completely recovered glutathione was seen in other organs. The GSSG level did not decrease significantly in the lung or liver but lowered significantly after 12 h and 24 h. The GSSG fraction in the amount of total glutathione was 10% or more in the lung and 5% or less in the liver or kidney. This finding indicated that the total glutathione level was mainly changed by the decrease in the GSH fraction. Cadmium in the lung increased to 7.3 ppm 3 h after Cd instillation and decreased to 2.5 ppm within 48 h. Cadmium in the liver and kidney gradually increased with time, and after 48 h reached 1.1 and 2.3 ppm, respectively. This indicated a transportation of Cd from the lung to these organs. Moreover, the early stage of Cd accumulation coincided with the total glutathione decrease in the organs. After Cd instillation, pulmonary, hepatic and renal Mt started to increase at 3 or 6 h, and markedly increased at 24 h or later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918798 TI - The production of hepatic cirrhosis in rats. AB - This study investigated the conditions necessary to produce a predictable yield of cirrhosis in rats. A previously published method, using carbon tetrachloride, was used as a basis for the study. Histopathology was used in a semi-quantitative manner to examine which observations could be used for the prediction of progression and final yield of cirrhosis. A comparison of different vehicles for oral carbon tetrachloride administration showed no effect of vehicle on the final yield of cirrhosis. Also, there were no observations during the study that should be used for prediction. Variability in the severity of hepatic impairment is an inherent feature of this model, and supporting histopathology is essential. We recommend a simple protocol for the initiation of cirrhosis in rats using carbon tetrachloride. PMID- 1918797 TI - Comparative studies of the covalent binding of [14C]-2-chloro-4-acetotoluidide by liver and kidney slices of the starling. AB - In tissue slices of female starlings, binding of [14C]-2-chloro-4-acetotoluidide (CAT) radioactivity to liver proteins was almost five times greater than binding to kidney proteins after 2 h of incubation. Binding to protein of liver slices increased in a log linear fashion with increasing CAT concentrations. Binding to protein of kidney slices also increased with increasing concentrations but not in a log linear fashion. Mixed-function oxidase inhibitors, SKF 525-A and alpha naphthoflavone, decreased binding to liver slices but did not affect binding to kidney slices. Anaerobic incubation conditions inhibited binding to both tissues. P-Hydroxymercuribenzoate and sodium cyanide did not affect the binding of radioactivity associated with [14C]-CAT to proteins of either liver or kidney slices. Diethyl maleate increased binding of the radioactivity to proteins of the kidney slices but not to liver slices. Cysteine also increased binding in kidney slices. Binding in liver slices did not increase significantly with cysteine. The cysteine-induced increase in protein binding in kidney slices did not appear to depend on the formation of sulfate from the metabolism of cysteine. There was no sex-dependent difference in starlings as to the binding of radioactivity in either liver or kidney slices. Male chicken kidney slices bound a much higher amount of radioactivity associated with [14C]-CAT than male starling kidney slices, while the liver slices bound comparable amounts. Male hamster liver slices bound much more radioactivity than did male starling liver slices. However, hamster kidney slices bound much less than did starling kidney slices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918799 TI - Differential scanning calorimetry to study the possible ternary complex formation between chlorhexidine, phosphatidylcholine and some nonionic tenzides. AB - The effect of chlorhexidine and its molecular complexes with some nonionic tenzides (Tween and Myrj series) on the phase transfer parameters of dipalmitoylphosphatidylcholine has been studied by differential scanning calorimetry. The application of principal component analysis facilitated the evaluation of the experimental data matrix. It was found that both the lipophilicity of the tenzide and the strength of interaction between chlorhexidine and nonionic tenzide had a considerable impact on some of the phase transition parameters of dipalmitoylphosphatidylcholine. These findings indicate the possible existence of ternary complexes. This ternary complex formation may cause a decrease of chlorhexidine activity in the presence of nonionic tenzides. PMID- 1918800 TI - Determination of hemoglobin through its peroxidase activity on chlorpromazine. AB - Chlorpromazine is an excellent chromogen for determining micro-quantities of hemoglobin. The oxidation of chlorpromazine by peroxidase activity of hemoglobin is coupled to a non-enzymatic reaction of second-order. Kinetic analysis of the overall system leads to a discussion about the optimal assay conditions. Spectrophotometric progress curves for the accumulation of the chlorpromazine cation radical during the reaction have been obtained, and further analyzed by non-linear regression. The use of a linear calibration curve of the enzymatic reaction rate against hemoglobin concentration is proposed for its determination. PMID- 1918801 TI - Preparation of unaltered hemoglobin from human placentas for possible use in blood substitutes. AB - Hemoglobin extracted from human placentas could be used as the basis of blood substitutes provided it could be prepared on a large scale with appropriate oxygen-binding properties. Unfortunately, the industrial conditions under which it is extracted, produce hemoglobin with high oxygen affinity and which is no longer influenced by the classical effectors. These characteristics were shown to be caused by a degradation of the alpha-chain brought about by an arginine carboxypeptidase present in the placental tissues and leading to the disappearance of the C-terminal arginine residue. This carboxypeptidase which is released from the tissues during the process of crushing the frozen placentas, degrades the protein during the chromatographic purification procedure. The addition of an inhibitor of this carboxypeptidase (for example, arginine) as soon as the placentas are thawed and during the chromatographic process, makes it possible to obtain placental hemoglobin with oxygen-binding properties quite similar to those of HbA prepared from peripheral venous blood. PMID- 1918802 TI - Selection of monoclonal antibodies for immunoaffinity chromatography: model studies with antibodies against soy bean trypsin inhibitor. AB - To facilitate selection of monoclonal antibodies for immunoaffinity chromatography, an ELISA screening procedure was developed. The assay is based on the avidin-biotin system and provides a profile of the monoclonal antibody which is based on the binding characteristics of the antigen binding site when exposed to different elution reagents. The elution profiles of 5 monoclonal antibodies to soy bean trypsin inhibitor (SBTI) were determined and for 2 of the antibodies the results obtained in the ELISA were verified using column experiments. The affinity constants were determined for the same 5 monoclonal antibodies and no correlation was seen with the ease of elution. The elution profiles presented here are easily obtained and the results indicate that a general screening procedure for suitable combinations of antibodies and elution conditions can be carried out using an elution ELISA assay when modified as described herein. PMID- 1918803 TI - Development of the human dorsal nucleus of vagus nerve: a morphometric study. AB - The development of the human dorsal nucleus of the vagus nerve was studied on serial sections of the brain of 10 fetuses at 16-40 weeks of gestation, an infant at 2 months of age and an adult of 63 years. A morphometric analysis revealed that the nucleus is divided into three subnuclei (caudal, dorsal and ventral) and that this subdivision is maintained from 16 weeks of gestation to adulthood. The early development of the nucleus is gradual between 16 and 40 weeks of gestation without the rapid growth phase apparent with the motor trigeminal, hypoglossal and facial nuclei. PMID- 1918804 TI - Comparison between muscle sympathetic nerve activity and calf vascular resistance with head-up tilting in humans. AB - The purpose of this study was to determine the relationship between muscle sympathetic nerve activity (MSA) to calf muscle and calf vascular resistance with head-up tilting in humans. In nine healthy volunteers, we performed simultaneous measurements of MSA using microneurography and calf vascular resistance using electrical impedance plethysmography in the same leg. The volunteers were laid on a tilt table and the examinations with head-up tilting (0 degrees, 30 degrees, 60 degrees) were performed. Corresponding to the increase in angles of head-up tilting, MSA and calf vascular resistance significantly increased. A statistically significant positive linear correlation was demonstrated between MSA and calf vascular resistance. These data suggest that impedance plethysmographic measurement of calf vascular resistance can be reliably used to assess the status of MSA with head-up tilting. PMID- 1918806 TI - Rate of bladder distension and hypogastric nerve activity in the cat. AB - The effect of two rates of bladder filling on hypogastric efferent nerve activity was examined in cats anaesthetised with a continuous pentobarbitone infusion. At each level of bladder pressure the amount of hypogastric efferent nerve activity was less at the higher filling rate. This result may reflect a volume effect absent in pressure-nerve activity relationships. When volume effects were allowed for, variation in filling rate appeared to have little influence on hypogastric nerve activity. PMID- 1918805 TI - Catecholamine projections to the spinal cord in the rat and their relationship to central cardiovascular neurons. AB - The organization of the neuroanatomical substrate which provides the supraspinal catecholaminergic innervation of the upper thoracic spinal cord in the rat was studied by means of retrograde labelling of neurons with primuline and other dyes, combined with simultaneous catecholamine fluorescence (FAGLU-method). It was shown that spinally projecting catecholaminergic neurons lie predominantly in the A6 and A11 groups, while a minority of these neurons are also located in the A1/C1 and A5 groups. The number of catecholamine-containing neurons in the A11 group in the rat was estimated to be 173 +/- 4. Most of them (up to 86%) were retrogradely labelled with primuline. The possible functional role of dopaminergic diencephalospinal, noradrenergic pontospinal, and adrenergic bulbospinal neuronal systems in cardiovascular control is discussed. PMID- 1918807 TI - Number and density of intrapancreatic ganglion cells in the chicken. AB - The avian pancreas contains numerous small ganglia in nerve bundles within the interlobular connective tissue. The present study assesses the number and density of intrapancreatic ganglion cells in the chicken. The number of ganglion cells in the pancreas was about 14,000 and the density was 18.0 cells/mm3. No ganglion cells were found in the pancreatic islet. The topographical distribution of ganglion cells suggests that they have a closer relationship with the acinus than with the pancreatic islet and, furthermore, closer with B-islets than with A islets. PMID- 1918808 TI - Neural control of urinary sodium excretion during hypertonic NaCl load in conscious rabbits: role of renal and hepatic nerves and baroreceptors. AB - We examined responses of renal nerve activity, urine flow, and urinary Na+ excretion to a hypertonic NaCl infusion in chronically instrumented conscious rabbits with unilateral renal denervation. The intravenous infusion of 20% NaCl, at 0.2 ml/min for 30 min, increased plasma osmolality by 27 +/- 5 mOsm/kg, and plasma Na+ by 16 +/- 3 mEq/l, and decreased hematocrit by 5 +/- 1%. These changes were accompanied by a marked decrease in renal nerve activity by 82 + 7%. Urine flow and urinary Na+ excretion increased gradually and peaked at the end of infusion. The innervated kidney excreted 23.3 +/- 3.3 ml urine and 5.5 +/- 0.7 mEq Na+ for the subsequent 60 min. However, the contralateral denervated kidney excreted only 9.5 +/- 2.0 ml urine and 2.2 +/- 0.6 mEq Na+; these values were significantly less than those of the innervated kidney. To examine the role of the sinoaortic and cardiopulmonary baroreceptors and the hepatic nerves in the response of renal nerve activity to the hypertonic NaCl infusion, renal nerve activity was examined in conscious rabbits with sinoaortic baroreceptor denervation (SAD) plus vagotomy and/or section of the anterior and posterior hepatic nerves (SAPH). In rabbits with SAD plus vagotomy or SAPH, the NaCl infusion also decreased renal nerve activity. After combining SAPH and SAD plus vagotomy, the decrease in renal nerve activity was completely blocked. These results indicate that hypertonic NaCl infusion elicits a marked decrease in renal nerve activity which is mediated predominantly by sinoaortic and cardiopulmonary baroreflexes and the hepatic nerves, and that the decrease in renal nerve activity plays an important role in the augmentation of renal function. PMID- 1918810 TI - Effects of centrally administered angiotensin on sympathetic nerve activity and blood flow to the kidney in conscious rats. AB - The effects of intracerebroventricular (i.c.v.) administration of different doses (10 pg-100 ng) of angiotensin II (AII) on renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MAP), heart rate (HR), renal blood flow and femoral blood flow have been examined in conscious rats. Administration of AII (10 ng) through a chronically implanted cannula induced an increase in MAP (20-22 mmHg), a decrease in HR (24 bpm), a decrease in RSNA by 57%, a decrease of femoral blood flow by 21% but no change in renal blood flow. The effects on MAP, HR and RSNA are greatly attenuated by the prior i.c.v. injection of an AII antagonist saralasin. In anesthetized rats, renal denervation significantly attenuated an increase in urinary sodium excretion induced by i.c.v. injection of AII. Since activation of the renal nerve is known to induce sodium reabsorption from the renal tubule and renin release, the relevance of the present finding is discussed in relation to the effect of AII on sodium excretion. PMID- 1918809 TI - Rapid phasic baroreceptor inhibition of the activity in sympathetic preganglionic neurones does not change throughout the respiratory cycle. AB - We tested the hypothesis that the inhibitory influence of rapid phasic arterial baroreceptor stimulation on activity in sympathetic preganglionic neurones is weaker in inspiration than in expiration. Using neurophysiological techniques, 59 single preganglionic neurones with typical reflex pattern of muscle vasoconstrictor neurones that projected in the cervical sympathetic trunk were analysed. The inhibitory modulation of the ongoing activity in these neurones by the pulsatile activation of the arterial baroreceptors was determined by constructing post-R-wave histograms separately for both respiratory phases (as indicated by the discharge in the phrenic nerve). Quantitative measurements showed that the inhibition of the activity in the preganglionic neurones following phasic stimulation of arterial baroreceptors by the pulse pressure wave was not statistically different in both respiratory phases, even with increased respiratory drive. PMID- 1918811 TI - Influence of reduced presynaptic myocardial norepinephrine stores on left ventricular contractility. AB - Many investigators have reported that myocardial norepinephrine content is decreased in congestive heart failure. However there have been no studies of how decrease in myocardial norepinephrine might influence myocardial contraction. To clarify whether decreased myocardial norepinephrine per se affects myocardial contraction, we observed the change in left ventricular contractility during 30 min of left stellate ganglion stimulation in control and acutely reserpinized dogs. We obtained left ventricular max dp/dt and left ventricular end-systolic pressure-segment length relationships as indicators of left ventricular contractility. Both parameters decreased after left stellate ganglion stimulation in reserpinized dogs (left ventricular max dp/dt: 2064 +/- 200 to 1608 +/- 168 mmHg/s, left ventricular end-systolic pressure-segment length slope 117 +/- 22 to 79 +/- 14 mmHg/mm, n = 8, P less than 0.05), while they did not change in controls. In reserpinized dogs, left ventricular norepinephrine content decreased to one-third that of controls before the stimulation, and further decreased after stimulation. These data indicate that lowered myocardial norepinephrine itself may be responsible for the negative effect on left ventricular contractility in congestive heart failure. PMID- 1918812 TI - Distribution and function of cholinergic receptors in the sheep detrusor muscle. AB - The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes. PMID- 1918813 TI - Assessment of spinal movement. 1954. PMID- 1918814 TI - Patients as personalities. 1955. PMID- 1918815 TI - Visual assessment of nail growth. 1962. PMID- 1918816 TI - Preparing illustrations for half-tone reproduction. 1952. PMID- 1918818 TI - Forensic art: a police artist's experience. PMID- 1918817 TI - Communication and the universities. 1963. PMID- 1918819 TI - Desk-top publishing using IBM-compatible computers. AB - This paper sets out to describe one Medical Illustration Departments' experience of the introduction of computers for desk-top publishing. In this particular case, after careful consideration of all the options open, an IBM-compatible system was installed rather than the often popular choice of an Apple Macintosh. PMID- 1918820 TI - [Vitrectomy in retinal detachment caused by diabetic retinopathy]. AB - We reviewed the surgical results obtained in 23 eyes that underwent vitrectomy for diabetic traction retinal detachment. Retinal reattachment was obtained in 75% of eyes, however the functional results were modest, owing to retinal changes related to diabetic retinopathy and/or longstanding macular detachment. Ambulatory vision was obtained in 60% of eyes. 8 eyes (40%) had final visual acuity of 1/20 or better. Four preoperative clinical findings were associated with a poor prognosis = absence of scatter retinal photocoagulation, dense vitreous hemorrhage, iris neovascularization and preoperative visual acuity reduced to "light perception". Iatrogenic retinal breaks were also associated with a poor prognosis. PMID- 1918821 TI - [Immunomorphological study of the vitreous body and subretinal fluid in vitreoretinal proliferation]. AB - Proliferative vitreoretinopathy (PVR) is a major complication of rhegmatogenous retinal detachment. Its pathogenesis remains poorly understood and the accurate nature of the growing cells on both surfaces of the detached retina has not been yet determined. We undertook an immunocytological study on 28 specimens of vitreous or subretinal fluid removed from patients with PVR. Five main types of cells could be identified: heavily pigmented cells, poorly pigmented ones, large totally unpigmented macrophage-like ones, smaller unpigmented cells and lymphocytes. Analysis of intravitreal pigment granules showed two different types of pigmented cells, those with lipofuscin and melanin and those with melanin without any granules of lipofuscin, which could originate from ciliary or iris pigment epithelia. Immunostaining procedures confirmed the epithelial non macrophagic lineage of the intravitreal and subretinal cells. Lymphocytes were only B cells. These results confirm the importance of proliferative process during the course of PVR and shows the involvement of other ocular structures other than the retinal pigment epithelium. PMID- 1918822 TI - [Epidemiology and prevalence of hereditary retinal dystrophies in the Northern France]. AB - The authors present part of a study concerning inherited retinal dystrophies as recorded among the inhabitants of the Nord-Pas-de-Calais region of France. This retrospective study, covering eighteen years (from 1972 to 1989) and covering a population of nearly 4 millions inhabitants, has enabled us to assess the prevalence of each disease. 1,660 cases have been detected and 650 pedigrees have been established. The spatial distribution of the patients in reference to their places of origin in relation to the spatial division of area into "communes" or districts roughly corresponded to the population density and revealed a few centres of dominant retinal dystrophies in rural areas. The analysis of the distribution and inheritance of the various forms of retinitis pigmentosa confirmed the results obtained in other recent and similar studies carried out in other countries. The age pyramid of the detected cases followed that of the population under surveillance. Detection of all dystrophies increased up to the age of 35, then followed the normal decreasing pattern for older generations. As for retinoschisis, detection usually took place in the first fifteen years after birth; for Stargardt's disease, it has occurred up to the age of 20 and for Best's dystrophy, the process was the most extensive and the slowest to appear. The global number of dystrophies studied, corresponded to a prevalence of 1:1,490, which allowed us to estimate that the number of cases in France was 33,800. If we apply the phenomenon to all the populations of the European Community, we must consider that more than 300,000 patients are now affected by disabling hereditary retinal dystrophies. PMID- 1918823 TI - [Correction of severe myopia by refractive lamellar keratoplasty without freezing]. AB - The analysis of 56 successive procedures for correction of severe myopia enables us to determine the indications of the two surgical techniques we use: Myopic keratomileusis or Myopic Epikeratophakia. The results are very different. They are reliable and steady throughout one year for certain myopias, but more uncertain for more severe ones. This led us to distinguish two subgroups: the first includes the initial myopia equal to or less than -15 dioptres, the second includes the more severe myopia. Epikeratophakia, always implemented using fresh lenticules corrects more severe myopias than keratomileusis (from -15 to -30 dioptres). So, the indication for epikeratophakia depends on the initial ametropia, as well as on refractive parameters such as keratometry. With the same myopia, an anterior curvature radius over 8.2 mm will render a myopic keratomileusis less efficient then a myopic epikeratophakia. The results with one year follow up are more predictable and stable for the first subgroup. The second group and those cases corrected by epikeratophakia had less predictable results. PMID- 1918824 TI - [Reoperation after radial keratotomy. When is it indicated?]. AB - In a series of 719 patients who underwent radial keratotomies, the authors report the results of pericentral deepenings 1 month and 1 year postoperatively because of undercorrection postoperatively. The improvement of residual myopia was 68.6% in the first group and 64.8% in the second group. There was no statistically difference between these two results. The dioptric improvement did not exceed 1.5 dioptre in all cases. PMID- 1918825 TI - [Solitary eosinophilic granuloma of the external wall of the orbit]. AB - Eosinophilic granuloma is a solitary form of histiocytosis X with a usually good prognosis. Sometimes spontaneous healing can even occur. The authors report a case of a 30-month-old boy who presented an eosinophilic granuloma of the lateral orbital wall. The correct diagnosis was obtained after computed tomographic scan followed by fine needle aspiration biopsy with histopathologic examination. The tumor increased rapidly, including a medial displacement of the globe and limitation of the eye movement. So chemotherapy (Vinblastine) with corticotherapy was performed. The clinical course was favorable, with no evidence of recurrence or systemic involvement. The originality of this case was the young age of the patient, the course and the efficacy of treatment. The authors emphasize the management of the disease. PMID- 1918826 TI - [Congenital serous cyst of the orbit with anophthalmos]. AB - The authors reported a case of orbital congenital serous cyst with anophtalmos. It was a third type of Duke Elder classification. Although it looked sporadic, this malformation is hereditary and due to a disharmony between optic cup growth and differenciation. Ultrasonography and scanner could confirm the diagnosis and helped to discard orbital and eyelid angioma and meningocele. After excision, a prosthesis must be adapted in the orbit. PMID- 1918827 TI - [Eye injuries caused by accidental projection of Javel's solution]. PMID- 1918828 TI - [Unnecessary surgery in cases of fully accommodative esotropia]. PMID- 1918830 TI - Abstracts of the 5th meeting of the European Neuroendocrine Association. Budapest, Hungary, August 25-28, 1991. PMID- 1918829 TI - [Unnecessary surgery in cases of fully accommodative esotropia. Response by Prof. P.V. Berard]. PMID- 1918831 TI - Human milk containing specific secretory IgA inhibits binding of Giardia lamblia to nylon and glass surfaces. AB - The effects of human milk, containing specific secretory IgA, on the adherence of Giardia lamblia trophozoites in the presence and in the absence of intestinal mucus in vitro were studied. It was found that the trophozoites treated with breast milk, containing specific secretory IgA to G. lamblia, showed a significant decrease (p less than 0.01) in adherence to nylon fibre columns and glass surfaces than did trophozoites treated with milk containing no SIgA antibodies. The adherence to glass surfaces was significantly more (p less than 0.01) in the presence of intestinal mucus than when the mucus was absent. Milk that did not contain specific secretory SIgA to G. lamblia did not decrease the adherence to glass surfaces either in the presence or in the absence of mucus. The fluorescence study revealed the binding of specific secretory IgA on the trophozoite surface. The results suggest that binding of SIgA antibodies in milk to G. lamblia trophozoites inhibits parasite adherence, thus protecting against this infection in breast-fed babies. PMID- 1918832 TI - Importance of age in evaluating effects of maternal and domestic hygiene practices on diarrhoea in rural Bangladeshi children. AB - To understand the roles of specific maternal and domestic hygiene practices in preventing diarrhoea, 611 rural children aged under 5 years in southeastern Bangladesh were studied. From July 1980 to June 1983, diarrhoeal episodes were recorded by weekly home visits, while observations on maternal and domestic hygiene were made yearly. Infants (aged 3-11 months) in households where mothers washed their hands (before handling food and after toilet use) and removed the child's faeces from the premises soon after defecation had 0.82 and 0.98 annual episodes respectively, fewer than those of their counterparts with 4.1 episodes. Diarrhoea was less frequent by more than 0.5 episodes in children in the age groups 12-23 and 24-35 months with 4.3 and 2.5 annual episodes respectively for the removal of faeces only. The use of handpump water at home was not associated with the frequency of diarrhoea in children, except in the age group 48-59 months, in a particular year of the study. PMID- 1918833 TI - Role of calcium and calmodulin in Giardia lamblia-induced diarrhoea in mice. AB - The unidirectional fluxes of Na+, Cl- and Ca2+ across the small intestinal epithelium of normal and Giardia lamblia-infected mice were studied in vitro in short-circuited tissue. Net secretion of Na+ and Cl- was observed in infected animals, whereas in non-infected (control) animals there was net absorption of Na+ ions and marginal secretion of Cl- ions. In infected animals, net absorption of Ca2+ was observed as compared to little secretion observed in control animals. Although the presence of Ca(2+)-ionophore in the medium resulted in a net secretion of Na+ and Cl- in controls, it could not cause any change in the fluxes of these ions in infected animals. Verapamil, a calcium channel blocker, reversed the effects of infection and Ca(2+)-ionophore. Further W7 (n-(6-aminohexyl)-5 chloro-1-naphthalene sulphonamide), a calmodulin antagonist, also reversed the effects of infection. The addition of the neurotoxin, tetrodotoxin caused net absorption of Na+, Cl- and net secretion of Ca2+ in the control group, but it could not produce any effect on the fluxes of these ions in the infected group. These findings demonstrate that, in G. lamblia infection, the secretion of Na+ and Cl- is associated with an increase in absorption of Ca2+ and an increase in calmodulin activity in intestinal microvillar core. These findings further suggest that the enteric nervous system plays a marginal role in Giardia infection. PMID- 1918835 TI - Diarrhoea associated with Escherichia coli O157 which do not produce verocytotoxins. PMID- 1918834 TI - Oral rehydration solution containing 90 millimol sodium is safe and useful in treating diarrhoea in severely malnourished children. AB - The safety and efficacy of standard oral glucose-electrolyte solution, containing 90 mmol of sodium per litre, was evaluated in the treatment of dehydrating diarrhoea among severely malnourished (marasmic) children. A total of 81 male children aged between 6 and 48 months were studied; 41 were in the malnourished group (study group: less than 60% of Harvard Standard weight-for-age) and 40 were in the well-nourished group (control group: 80% or more Harvard Standard weight for-age). Children of both groups could be rehydrated with standard oral rehydration solution (ORS) without encountering any clinical or biochemical complications. The results of this study lend support to the World Health Organization's concept of a unified formula of ORS for the treatment of all cases of acute diarrhoea, including severely malnourished children. PMID- 1918836 TI - Bibliography on diarrhoeal diseases. PMID- 1918837 TI - Bacteriologic studies of food and water consumed by children in Myanmar: 1. The nature of contamination. AB - To isolate major bacterial pathogens from children's food and drinking water, a 3 month study was conducted in a suburban community in Yangon, Myanmar. From the morning meals and stored drinking water of 208 randomly selected children, 775 food and 113 water samples were collected and were cultured using standard methods. Escherichia coli, Vibrio cholerae non-01, and Salmonella were isolated from 505, 28 and 6 food samples respectively, and E. coli and V. cholerae non-01 were isolated from 29 and 5 water samples respectively. Among the E. coli isolates, 8 produced heat-stable toxin (ST) and 3 were enteroinvasive. Nine V. cholerae non-01 produced cholera-like toxin. Of the 29 E. coli isolates from the samples of drinking water, 3 produced ST. All water samples were negative for Salmonella. The study underscores the importance of bacterial contamination of children's food and drinking water and stresses the need to improve environmental sanitation. PMID- 1918838 TI - Bacteriologic studies of food and water consumed by children in Myanmar: 2 Lack of association between diarrhoea and contamination of food and water. AB - The association between contamination of morning samples of food and water of 208 children aged 6-29 months and the incidence of diarrhoea was investigated for 3 months in Yangon, Myanmar. Contamination of the samples was determined by isolation of faecal coliforms (FC) by standard methods. The children were divided into three groups, high, medium and low, according to the proportion of food and water samples found to be contaminated. The incidence of diarrhoea was recorded by weekly recall. Of the 779 food samples, 504 (65%), and of the 860 drinking water samples, 187 (22%) were positive for FC. The association between food and water contamination and the incidence of diarrhoea was assessed by comparing the cumulative incidences in the high and medium groups with that in the low group which served as reference. Diarrhoea risk ratios (RR) for children in the medium and high contamination groups (food, RR = 1.04 in medium and 0.78 in high vs 1 in low; water, RR = 0.73 and 0.73 vs 1) were not significantly different from those who were in the low-contamination group even after controlling for the confounding variables. PMID- 1918840 TI - Corrosive acid-induced esophageal intramural pseudodiverticulosis. A study of 14 patients. AB - Esophageal intramural pseudodiverticulosis (EIP) is a rare disease, characterized by multiple, small flask-shaped diverticula in the esophageal wall, and best demonstrated on single-contrast barium examination. Though the condition is often associated with reflux esophagitis, Candida esophagitis, and esophageal dysmotility, corrosive-acid injury is not a commonly recognized cause. In a radiological study involving 59 patients with sequelae of corrosive-acid injury of the upper gastrointestinal (GI) tract, evaluated over a 5-year period, 14 cases (23.7%) of EIP were found. Esophageal stricture was a constant association; the diverticula tended to involve either the entire length of the stricture or its upper part. There was, however, no correlation between the length of the stricture and number of diverticula (p greater than 0.05). Endoscopic dilatation resulted in relief of dysphagia, and the diverticula regressed in number of disappeared altogether. Our experience suggests that EIP is a common sequelae of esophageal acid injuries, and that diverticula tend to form at the site of initial contact between acid and susceptible esophageal mucosa. Stricture dilatation leads to reduction or total disappearance of the diverticula. PMID- 1918839 TI - The epidemiology of diarrhoeal diseases in southeastern China. AB - In a community survey of 19,410 people for 12 months in southeastern China (Fujian Province), the overall annual incidence rate of diarrhoea was 729.9 episodes/1,000 population. The incidence varied with different age groups; children aged under five years had the highest rate, 2.25 episodes per child per year. A bacterial pathogen was isolated from 883 cases (44.03%), and 147 (14.76%) strains from 996 healthy controls. Enterotoxigenic Escherichia coli, enteropathogenic E. coli, and Shigella species were the most frequently isolated bacterial pathogens. Isolation was highest during the hot summer months. The investigation showed that the diarrhoea incidence was related to the status of economy, education, healthy, hygiene, food, and water. PMID- 1918841 TI - Endoscopic injection of alcohol to stop peptic ulcer hemorrhage. Experience with 115 cases. AB - In a period of 33 months, we performed endoscopic injection with pure alcohol (PA) to try to stop peptic ulcer hemorrhage in 115 patients. The sex ratio (M/F) was 104/11. The average age was 59.5 +/- 1.5 years (mean +/- SEM). Sixty-two patients (53.9%) were in shock before endoscopic injection. Thirty-three (28.7%) had spurting hemorrhage, 31 (27%) oozing hemorrhage, and 51 (44.3%) nonbleeding visible vessels (NBVV). We obtained initial success in 92 patients (80%). Rebleeding episodes occurred in 7 patients (7.6%) within 7 days of endoscopic injection. Five of those who rebled received a second injection with PA and bleeding stopped in three of them. In 88 (76.5%) patients, therapy was ultimately successful. The duration of hospitalization was 5.1 +/- 0.6 days (mean +/- SEM). The total volume of blood transfused was 1450 +/- 192 ml (mean +/- SEM). We conclude that endoscopic injection is an inexpensive, convenient, and effective means for arresting peptic ulcer hemorrhage. It can be used as the first therapeutic approach. PMID- 1918842 TI - Comparison of sucralfate and ranitidine twice daily in duodenal ulcer treatment: a multicenter randomized double-blind study. AB - Sucralfate and ranitidine were compared in the treatment of duodenal ulcer in this multicenter, randomized, double-blind study. A total of 165 patients with endoscopically proven duodenal ulceration were included in the trial and randomized to treatment with sucralfate, 2 g b.i.d. (morning and evening with an empty stomach), or ranitidine, 150 mg twice daily. All patients were endoscopically examined after 4 and, if unhealed, 8 weeks. Of the patients considered suitable for analysis at 4 weeks, 73.5% (61 of 83) of the sucralfate group demonstrated healing of the ulcer in comparison with 63.3% (50 of 79) of the ranitidine group. At 8 weeks cumulative healing rates were 89% (74 of 83) and 84.8% (67 of 79), respectively. When smokers were considered separately, healing rates at 4 weeks were 69.2% (36 of 52) for sucralfate and 53.3% (24 of 45) for ranitidine. At 8 weeks cumulative healing rates were 92.3% (48 of 52) and 77.7% (35 of 45), respectively (p less than 0.05). Overall, there was no difference in the two groups regarding symptom relief and side effects. These results suggest that these drugs are equally effective in the short-term treatment of duodenal ulcer, although in smokers sucralfate appears to be more effective than ranitidine. PMID- 1918843 TI - Folate biochemical modulation regimen for the treatment of gastric cancer. AB - Twenty patients with metastatic gastric cancer were treated with methotrexate (MTX, M), 100 to 160 mg/m2 at 0 h, and, in sequence, 5-fluorouracil (FU, F), 600 to 1000 mg/m2 at 4 h; leucovorin (LV, L), 200 mg/m2 at 18 h, then 20 mg/m2 every 6 h x 12; 5-fluorouracil, 600 mg/m2 at 19 h; and high-dose cisplatin (DDP, P), 100 mg/m2 at 20 h. In addition, they were treated with a continuous 5 fluorouracil infusion, 1000 mg/m2/24 h from 18 h to 114. There were 8 complete and 6 partial responses among the 16 patients with measurable tumors. Five patients, each with one remaining clinical site of disease, received supplementary regional therapy: three received intraperitoneal therapy, two received hepatic arterial therapy. Intraperitoneal therapy and hepatic artery therapy each produced one complete response. Median survival was 16 months for all patients, and 25% survived 2 years. In comparison with matched patients, both response rates and survival improved twofold. PMID- 1918844 TI - Adult T-cell leukemia/lymphoma with gastric lesions. Report of three cases. AB - We describe three cases of adult T-cell leukemia/lymphoma (ATL) with malignant cell infiltration into the stomach. Case 1, a 63-year-old man, had a large ulcerative lesion on the lesser curvature of the upper stomach. Case 2, a 44-year old man, had an irregular depressed lesion simulating a IIc-type early gastric cancer on the posterior wall of the mid portion of the stomach. Case 3, a 58-year old man, had multiple irregular depressed lesions on the lesser curvature of the lower part of the stomach. In all cases, histologic examinations of the biopsy specimens confirmed ATL-cell infiltration into the stomach. In cases 1 and 2, repeated roentgenographic and endoscopic examinations revealed the characteristic changes of the gastric lesions over the course of time. PMID- 1918845 TI - Piezoelectric lithotripsy in the treatment of symptomatic gallstone patients. A 12-month follow-up. AB - Between January and May 1989, 65 patients with symptomatic gallbladder stones were treated with extracorporeal piezoelectric lithotripsy (EPL) and supplementary dissolution therapy with oral bile acids. In 98% of the patients, fragmentation of stones was achieved. On average, each patient received 3.18 treatments. In addition to attacks of colic and asymptomatic changes in laboratory parameters, one hematoma of the gallbladder and one of the liver were observed, together with pancreatitis and cholecystitis in two patients each. During the follow-up period, three patients developed symptomatic bile duct stones. An endoscopic retrograde cholangiopancreatography (ERCP) with papillotomy was performed on four occasions, while one female patient had to undergo urgent cholecystectomy for inflammation of the gallbladder and empyema. Six months after the initial treatment, 36 (55%) patients were free of stones, while the stone free rate after 12 months was 64.5% (41 of 65). Ninety percent of the patients with a solitary stone less than or equal to 2 cm in diameter became stonefree within a year. Extracorporeal piezoelectric lithotripsy is clearly a feasible procedure for the treatment of certain gallstone patients. PMID- 1918846 TI - Myxedema ascites. Report of two cases and review of the literature. AB - Ascites is a well-known but uncommon occurrence in hypothyroid patients. We describe two patients with clinical ascites that resolved completely on thyroid replacement therapy. Our review of the literature found 21 well-documented cases of myxedema ascites. Prominent features of this condition include a high protein content of the ascitic fluid (greater than 2.5 g/dl), a high albumin serum ascites gradient, a long duration of the ascites, and its resolution on thyroid replacement. We also found a slight female predominance. The exact mechanisms responsible for ascites accumulation are unknown and some of the hypotheses are discussed. We conclude that ascites associated with hypothyroidism is rare but must be recognized early since thyroid replacement is definitive therapy. PMID- 1918847 TI - New perspectives in the diagnosis of Echinococcus disease. AB - Echinococcosis, an endemic disease on the Asian continent, is caused by the tapeworm Tenia Echinococcus, which produces cysts in the liver and other organs. I reviewed 157 patients with hydatid disease of the liver. The hydatid cysts were single in 125 patients and predominantly in the right lobe, but multiple in 31 patients, localized in both lobes or in the lung, spleen, pancreas, heart, or peritoneum. In 14 patients, early complications were manifested by rupture of the cyst into the biliary tract, the lung, or the peritoneum. Infection of the cysts was rare. Late postsurgical complications, noted in 10, were the development of an abscess or cirrhosis. I evaluated the importance of computed tomography (CT) in the diagnosis of hydatidosis of the liver and other visceral organs: It made a correct and accurate diagnosis in 96% of 157 patients. But, in ruptured or infected cysts, CT scans could not distinguish between a hydatid cyst and an abscess. Surgery is still the treatment of choice in hydatid disease. It is absolutely indicated in complicated cases, and is easy and curative in uncomplicated ones. I have used Mebendazole in 18 patients for 2 years without significant benefit, except in two patients with disseminated hydatidosis. Mebendazole stabilized the disease. PMID- 1918848 TI - Effect of intraportal nitroglycerin on portosystemic hemodynamics in patients with cirrhosis: comparison with i.v. route. AB - We observed 18 patients with portal hypertension and cirrhosis to compare the effects of intraportal nitroglycerin on portosystemic hemodynamics with the i.v. route. Patients received 1 microgram/kg/min of nitroglycerin intravenously (n = 9) or the same dose of nitroglycerin directly into the portal vein (n = 9). Both routes of nitroglycerin significantly reduced mean arterial pressure and this effect was higher with the i.v. route (-28.0% versus -19.3%, p less than 0.02). The portal pressure, as evaluated by the portal venous pressure gradient or hepatic venous pressure gradient, was also reduced significantly in both groups. The fall in portal pressure was higher in the intraportal group, but the difference was not significant (intravenous versus intraportal, -23.9 versus 25.1% in portal venous pressure gradient, -25.2 versus -33.4% in hepatic venous pressure gradient). The hepatic blood flow was maintained despite the significant reduction in portal pressure by both routes. These results indicate that intraportal nitroglycerin decreases portal pressure with a smaller effect on systemic hemodynamics than the i.v. route. We conclude that the oral administration of nitroglycerin, which is a pathway equivalent to the intraportal route, may be more useful than the i.v. (i.e., sublingual) route in the treatment of portal hypertension. PMID- 1918849 TI - Esophageal dysmotility from a small esophageal granular cell tumor. AB - Although typically small and submucosal, esophageal granular cell tumors frequently produce dysphagia. Esophageal manometry and a cine-esophagram in a patient with a 7-mm-wide esophageal granular cell tumor and dysphagia showed esophageal aperistalsis and a hypertensive lower esophageal sphincter that relaxed normally with swallowing. This finding suggests that dysmotility may contribute to the dysphagia frequently attributed to this tumor. This tumor is commonly believed to originate from Schwann cells and has a propensity to encompass and disrupt nerves that could produce the abnormal motility. Esophageal manometry is recommended when a small nonobstructing granular cell tumor is found in the evaluation of dysphagia. PMID- 1918850 TI - Hypertrophic gastropathy symptoms responsive to prednisone. A case report and a review of the literature. AB - We describe a 33-year-old man with giant hypertrophic gastropathy (Menetrier's disease), which, on operative biopsy of the stomach, showed a significant inflammatory component. The patient was treated with prednisone and quickly responded. Although a review of the literature revealed only two cases similarly treated, with equivocal results, spontaneous remission, does occur. Symptoms associated with this disease may respond to corticosteroids, which may offer effective therapy while awaiting involution of the gastropathy. Thus total gastrectomy may be avoided. PMID- 1918851 TI - Autoimmune hemolytic anemia in ulcerative colitis. A case report with review of the literature. AB - Autoimmune hemolytic anemia is a rare complication of ulcerative colitis. This report chronicles a patient successfully treated with steroids, and reviews treatment in previously reported cases. The fact that 21% of patients recovered with steroid therapy encourages a conservative approach before surgery is considered. PMID- 1918852 TI - Infectious endocarditis after fiberoptic sigmoidoscopy. With a literature review. AB - Infectious endocarditis is a feared complication of procedures causing bacteremia. Gastrointestinal procedures cause bacteremia, but are seldom followed by infectious endocarditis. Of nine cases found in the English literature, only five have convincing evidence that endocarditis resulted from the gastrointestinal procedure. I present a new case of endocarditis due to Streptococcus sanguis type II after fiberoptic sigmoidoscopy. PMID- 1918853 TI - Nodular regenerative hyperplasia of the liver in idiopathic hypereosinophilic syndrome. AB - We report a 52-year-old man with idiopathic hypereosinophilic syndrome and nodular regenerative hyperplasia of the liver. We postulate that nodular regenerative hyperplasia may be the result of an eosinophil-induced vascular lesion. PMID- 1918855 TI - Budd-Chiari syndrome complicating pre-eclampsia: diagnosis by magnetic resonance imaging. AB - A 25-year-old primigravida with third-trimester pre-eclampsia developed severe right upper quadrant pain, marked serum aminotransferase elevation, and disseminated intravascular coagulation after cesarean delivery. Computed tomography of the liver showed a right hepatic abnormality that on magnetic resonance imaging had the appearance of hemorrhage; partial thrombosis of the right hepatic vein extending to the inferior vena cava was also seen. Anticoagulation was begun and the patient completely recovered; follow-up imaging 8 months later was normal. This case suggests that nonfatal forms of Budd-Chiari syndrome may complicate pre-eclampsia; predisposition to partial venous outflow obstruction in the pre-eclamptic patient may be pathogenetically related to disseminated intravascular coagulation. This entity may be clinically confused with, or misdiagnosed as, spontaneous hepatic hemorrhage, with or without capsular rupture. In such circumstances, magnetic resonance may be diagnostically useful. PMID- 1918854 TI - Floating common bile duct stones. A cause of a false negative endoscopic retrograde cholangiogram. AB - Endoscopic retrograde cholangiography (ERC) is the "gold standard" for the preoperative diagnosis of choledocholithiasis. Air bubbles that can cause a false positive ERC are differentiated from stones by their response to gravitational maneuvers: bubbles rise while stones sink. We report a patient with round, floating common bile duct stones that mimicked air bubbles to be the reason for a false negative ERC. PMID- 1918856 TI - Cystic changes in gastric glands after gastric surgery and in the intact stomach. AB - Cystic changes of gastric mucosal glands have been described mainly after gastric operations, and like intestinal metaplasia and dysplasia, they may represent a premalignant condition. Their association with gastritis raises the possibility of their being secondary to the inflammatory process. Enterogastric reflux of duodenal contents, local chronic ischemia, and inflammatory reaction as a result of gastric surgery and suture at gastroenterostomy have been considered responsible for this lesion. In 18 of 157 consecutive patients (11.5%) who underwent endoscopic gastric biopsy within a year we found cystic changes of gastric mucosal glands. Cystic changes were present in 43% of 30 patients after gastric operation for duodenal ulcer disease, within an average of 8.4 years in contrast to only 4% of patients with an intact stomach. This change is statistically significant (Z = 1.97, (p less than 0.05) and suggests that there is a cause-and-effect link between the operation and the development of cystic lesions. In three patients we traced the original operative specimen, and in none did we find cystic changes. All the cases were associated with chronic gastritis; mild dysplasia was found in four (22%). The cystic glands were shown (by alcian blue-periodic acid-schiff staining) to secrete neutral mucin like normal gastric glands, and unlike dysplastic glands or intestinal metaplasia where acid mucin is characteristic. Thus, our findings suggest an inflammatory cause for the cystic glandular change (reactive, hyperplastic change of glands), and suggest that it is probably not a preneoplastic state. PMID- 1918857 TI - Massive subcapsular fibrosis of the liver: ultrasonic and computed tomographic characteristics. AB - Massive and diffuse subcapsular fibrosis of the liver was detected in two patients with chronic liver disease. The subcapsular layer consisted of inflamed fibrous tissue containing rare portal tracts and myriads of bile ducts, indicating loss of subcapsular hepatocytes and their replacement by connective tissue. In the early evolutive phase, massive and diffuse subcapsular fibrosis of the liver appears on computed tomography (CT) scan as a low-density band, which merges with the hepatic parenchyma and is enhanced by contrast on dynamic imaging; it is undetectable by ultrasonography. In the advanced phase, it is easily recognizable by ultrasonography as a perihepatic sonolucent band and by CT scan as a low-density band, which is well demarcated from the hepatic parenchyma and is not enhanced with the dynamic technique. PMID- 1918858 TI - Erythromycin as therapy for acute colonic pseudo-obstruction (Ogilvie's syndrome) PMID- 1918859 TI - Brucellar hepatic abscess. PMID- 1918860 TI - Massively bleeding gastrosplenic fistula following cytostatic chemotherapy of a malignant lymphoma. PMID- 1918861 TI - Chylous ascites with pericardial and pleural effusions in congenital lymphedema. PMID- 1918862 TI - Orthotopic liver transplantation for cholesteryl ester storage disease. PMID- 1918864 TI - An epidemiological study of malaria in a north-Indian district. AB - A retrospective epidemiological study was carried out in Gurgaon District of Haryana, wherein data on malaria for a period of more than three decades (1958 1989) obtained from various sources were analysed. The study revealed a rise in the incidence of this disease from midsixties onwards and reached peak in 1976. Subsequently, there has been a gradual and sustained decline, possibly due to better implementation of Modified Plant of Operations (M.P.O.) in a more realistic and rational manner. Various malaria-metric indices like A.P.I., A.B.E.R., S.F.R., etc, have been analysed and attempts made to compare these parameters with that of Haryana State as well as with all India average for last few years. The analysis of the cases according to species, age of patients, seasonal incidence and temporal and spatial distribution have also been discussed. PMID- 1918863 TI - Elimination of neonatal tetanus: 1995. AB - India aims at the elimination of neonatal tetanus by 1995 by providing TT immunization services to all pregnant women in the country. Strengthening of the surveillance system is part of the strategy for the elimination of neonatal tetanus. There is a wide range of performance at state and district level. Many states have the potential of achieving the difficult and challenging goal of neonatal tetanus elimination within a few years. PMID- 1918865 TI - Acute respiratory infection in children--a survey in East Godavari district of Andhra Pradesh. AB - A survey was carried out in East Godavari district of Andhra Pradesh to determine the magnitude of the problem of Acute Respiratory Infection (ARI) in children below five years of age. ARI associated mortality rates were found to be 15 times higher in infants than in the 1-4 year age group. However, overall ARI associated mortality was only 2.01 per thousand with an estimated case fatality ratio of 0.4 per thousand. A reverse trend in morbidity was noted in which 2-week incidence of ARI was more in 1-4 years age group than in infants. There is a need to standardize diagnosis and treatment of ARI disease in the district in order to eliminate wasteful use of antibiotics. PMID- 1918866 TI - Seroprevalence of HIV infection in Himachal Pradesh. AB - Serum samples from 2645 individuals representing all the twelve districts of Himachal Pradesh were screened for antibodies to Human immunodeficiency virus (HIV), employing ELISA test. These were categorised into four major high risk groups, viz, patients attending STD clinics (1305), voluntary blood donors (1012), hospital staff dealing with blood and blood products (200) and foreign nationals (128). No evidence of HIV infection was found in Himachali population. Two foreign nationals were repeatedly found positive for HIV antibodies by ELISA test and these were confirmed by Western Blot technique. PMID- 1918867 TI - Immunity against diphtheria in the age group 15 to 25 years. AB - Levels of diphtheria antitoxin in 254 serum samples were estimated in subjects in the age group 15 to 25 years with no previous history of immunisation against diphtheria using indirect haemagglutination test. All the individuals showed more than 0.03 IU/ml of diphtheria antitoxin level. This indicates that the age group studied was not susceptible to diphtheria. No significant relationship could be, however, ascertained between diphtheria antitoxin level and epidemiological factors like age, area (rural/urban), socioeconomic status, family size, education status and religion. PMID- 1918868 TI - Persistence of Vibrio cholerae in inter epidemic period--preliminary observations on analysis of water. AB - Out of the 61 water samples collected from hand pumps and wells from cholera endemic areas of Varanasi City, Vibrio cholerae non 01 was detected in only one sample. However, seven (18.9 per cent) samples out of 37 samples of river water were positive for V. cholerae non 01. None of the samples showed Vibrio cholerae. These observations indicate transmission and dilution of Vibrio cholerae bacillus in environment. PMID- 1918869 TI - Blood Cholinesterase monitoring in spraymen involved in malathion spraying--a health protection measure. AB - The blood Cholinesterase (ChE) level of malathion in spraymen is continuously monitored through a "built-in warning system" existing under NMEP since the introduction of malathion spraying. The data available from the States of Maharashtra, Punjab and Gujarat revealed that, in spraymen of Punjab, the ChE level in 1988 and 1989 remained normal in about 99.8 per cent spray personnel, and in 1 out of 381 workers, the ChE level fell to 62.5 per cent during 1989. In Gujarat and Maharashtra, the normal level of ChE was maintained in nearly 88 and 98.4 per cent of spray personnel respectively during the spraying period. The ChE level fell to 62.5 per cent in 11.9 per cent of spray staff in Gujarat during 1987 and in 1.5 and 1.6 per cent persons during 1988 and 1989 respectively in Maharashtra. Only in three cases (0.07 per cent) out of 4,100 in Maharashtra showed depression in ChE to 50 per cent in 1988. In none of the above mentioned cases, there was any parasympathetic overstimulation or uneasiness, etc, even then they were withdrawn from spray and were given rest and where needed medical care. PMID- 1918870 TI - Pattern of rice cultivation and anopheline breeding in Koraput district of Orissa state. AB - The potentiality of rice fields in anopheline vector breeding in Koraput district was studied in two agricultural seasons--rubi and kharif. Altogether, 17 species were recorded from the rice fields. The terraced stream bed paddy-fields with a perceptible water flow in top-hill areas support heavy breeding of the principal vector A. fluviatilis at all stages of paddy growth. A. culicifacies and A. annularis breeding became scarce when the paddy plants reached a height of 80 cm. Vector species formed 2 per cent in rabi and 32 per cent in kharif of the anopheline fauna from the paddy fields and the maximum production was during early stage of paddy growth or after harvesting. PMID- 1918871 TI - Biochemical and ultrastructural studies induced by phanquone on Entamoeba histolytica NIH-200. AB - The action of phanquone on the incorporation of (14C)1-DL-valine and (14C)-8 adenine in TCA insoluble fractions of Entamoeba histolytica was examined as indices of RNA and protein synthesis respectively. The former was found to show greater sensitivity to the drug in terms of the effect manifested in the dose response curves for these parameters. Electron microscopic investigations with increasing concentrations of the drug demonstrated progressive vacuolization with concomitant dissolution of ribosomal helices. The drug had no significant effect on nucleus and plasma membrane even at concentration as high as 200 micrograms/ml. PMID- 1918872 TI - Isolation of Salmonella senftenberg from different clinical sources. PMID- 1918873 TI - Liver steatosis in hypobetalipoproteinemia. A case report. AB - A case of hypobetalipoproteinemia is described; a 16-year-old girl had been suffering for nearly 2 years from diffuse abdominal pain. The only clinical features were liver steatosis, slightly increased amino transferases and an incipient polyneuropathy. No sign of malabsorption or gastrointestinal disease was found. She had extremely low levels of cholesterol and triacylglycerol in her serum, slightly decreased serum phospholipids and normal HDL-cholesterol levels. Apolipoprotein B-100 was approx. 8% of normal, whereas B-48 was present at essentially normal levels. Electron microscopy of lipoprotein particles showed normal morphology of LDL. Examination of close relatives showed no abnormalities. Southern blots revealed no major deletions or rearrangements at the genomic level. Although rare, a- and hypobetalipoproteinemia should be considered as possible etiologies in patients with unexplained steatosis in the liver. PMID- 1918874 TI - Biliary secretion of trace elements and minerals in the rat. Effects of bile flow variation and diurnal rhythms. AB - Effects of bile flow variations on bile secretion of trace elements were systematically evaluated by Proton-Induced X-ray Emission (PIXE) in the unanesthetized rat: (i) longitudinally for a 9 day-period of bile drainage; (ii) continuously for a period of 24 h, to include circadian rhythm and (iii) during exogenous bile salt administration. Potassium and Ca were determined for comparative purposes. In rat bile, six trace elements could always be detected by PIXE (Fe, Zn, Cu, Mo, Mn, Br); occasionally some V, Cr, Sr and Pb was found. Se could not be detected in bile. Bile-plasma concentration ratios of the elements could arbitrarily be divided into three groups: Fe, Zn and Se less than 1; Ca, K, Cu, Mo and Br approx. 1 and Mn much greater than 1. After interruption of the enterohepatic circulation, bile flow and bile salt concentration dropped sharply within 4 h to 36% and 4% of their initial values, respectively. Output rates of K, Ca, Mo, Br, Zn and Fe closely followed the decrease in bile flow; bile secretion of Mn and Cu, on the other hand, was minimally affected. A circadian rhythm was observed for all detectable elements; during the night period, secretion rates of Zn, Fe, Ca and K increased maximally by 60-80% and that of Mn, Mo, Br and Cu by 30-50%. Bile salt output and bile flow increased maximally by 70% and 50%, respectively, in the same time interval.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1918875 TI - Effect of glucose and branched chain amino acid (BCAA) infusion on onset of liver regeneration and plasma amino acid pattern in partially hepatectomized rats. AB - Immediately after 70% hepatectomy, rats were infused via the jugular vein with one of the following solutions: saline, 3% or 8% glucose solution, 3% BCAA solution, 8% Nutramin (17% BCAA) or 8% Nutramin enriched with BCAA (47% BCAA). Rats were killed 18, 21, 24 and 30 h after partial hepatectomy. The course of liver regeneration was assessed from incorporation of labeled thymidine into DNA and from hepatocyte mitotic activity. After partial hepatectomy a decrease of glycemia and increase of plasma phenylalanine concentrations were observed. Glucose infusion had a pronounced inhibiting effect on the onset of liver regeneration. The decreased incorporation of labeled thymidine into DNA and the decreased hepatocyte mitotic activity in glucose-infused rats were associated with higher plasma concentrations of tyrosine and phenylalanine. Parenteral administration of 3% BCAA solution and 8% Nutramin enriched with BCAA had a favourable effect on the onset of liver regeneration after partial hepatectomy compared with glucose- and Nutramin-infused groups. In BCAA-infused rats elevated levels of BCAA and decreased concentrations of tyrosine and phenylalanine were noted. PMID- 1918876 TI - Metabolic responses to intermittent hepatic dearterialization in the rat. AB - Hepatic dearterialization is a palliative treatment for irresectable liver tumours. In the current study, the metabolic consequences of hepatic dearterialization were examined in the rat. Liver glycogen content was reduced to an average of 84% following 60 min dearterialization and was further reduced to an average of 16% following 60 min reperfusion. Plasma concentration of beta hydroxybutyric acid was elevated by an average of 65% following 60 min hepatic dearterialization. In contrast, hepatic dearterialization did not alter cholesterol and triglyceride plasma levels. In addition, the hepatic activity of hepatic lipase was reduced by 29% after 60 min of hepatic dearterialization, a reduction which remained after 60 min of reperfusion. Clearance of intravenously administered antipyrine, which reflects the activity of liver microsomal enzymes, was reduced by 37% after 60 min of hepatic dearterialization. In conclusion hepatic dearterialization is accompanied by marked activity in the processes related to carbohydrate, lipid and xenobiotic metabolism. These effects should be taken into account when treating patients with hepatic dearterialization. PMID- 1918877 TI - Serum HBV DNA detected by PCR in dot blot negative HBV chronic carriers with active liver disease. AB - A group of forty-nine HBV chronic carriers with histologically confirmed active liver disease and undetected serum HBV DNA by dot-blot hybridisation were re investigated using the polymerase chain reaction (PCR) for amplification of serum DNA. The group comprised 16 persistently serum HBeAg-negative and thirty-three anti-HBe-positive patients. The use of PCR followed by Southern blot analysis has increased the sensitivity of HBV DNA detection to about 10-50 virions per ml of serum. Our results showed 14/16 (87.5%) of the HBeAg-positive group and 27/33 (81.8%) of the anti-HBe group to be positive for HBV DNA using PCR. Of the nine cases where HBV DNA was undetected four were positive for markers of hepatitis delta virus (HDV) infection. Demonstration of low level HBV replication associated with active liver disease in chronic HBV carriers where it was previously undetected meets a basic requirement for the proposed role of cytotoxic T lymphocyte-mediated immunopathogenesis in chronic hepatitis B and suggests a combined antiviral and immunotherapeutic approach to achieve eradication of the infection. PMID- 1918878 TI - Prognostic significance of pre-S2 antigen and antibody in fulminant hepatitis B. Evidence for heterogeneous serological responses. AB - Serial sera were collected prospectively and from early on in the clinical course of ten patients with fulminant hepatitis B. These were analysed for HBV DNA (dot blot technique), HBsAg, HBeAg, pre-S2-Ag and their respective antibodies. Two patterns emerged in nine of the patients. The first and well-recognised pattern of rapid clearance of antigens and appearance of antibodies was seen in four patients, all of whom survived. The second pattern seen in five patients was one of persistence of HBsAg and pre-S2 antigen and failure to detect antibodies but only one patient survived. The first pattern may reflect a more rapid cessation of virus replication and this may favour liver cell regeneration and recovery. In contrast, the second pattern may indicate continuing virus replication and liver cell damage which could contribute to the high mortality in some patients with fulminant hepatitis B. PMID- 1918879 TI - Liver transplantation in carriers of the HBsAg. PMID- 1918880 TI - Serum hyaluronate as a marker of hepatic derangement in acute liver damage. AB - Twenty patients with paracetamol(acetaminophen)-induced acute liver damage of varying severity were studied longitudinally with assessment of clinical state, standard liver function tests and radiometric hyaluronate (HYA) assay (Pharmacia). In patients (n = 6) who developed coma, HYA rose rapidly with clinical deterioration to reach a median value of 27,510 micrograms/l, 7 days post-ingestion, which was significantly higher (p less than 0.005) than in patients (n = 7) who exhibited only marked derangement of liver function tests without evidence of encephalopathy, HYA median value of 3240 micrograms/l. These peak values showed no correlation to the peak values of serum alanine aminotransferase (ALT). A third group of patients (n = 7) who were treated with N acetyl cysteine, did not exhibit any evidence of liver failure and showed no significant rise in levels of HYA or ALT. The data demonstrate that HYA is a rapidly changing marker of liver derangement which appears to follow the clinical course of the patient. The increase to extremely high levels in patients with hepatic encephalopathy, suggests that there is a reversible defect in the hepatic endothelial cell HYA receptor, possibly due to endothelial cell damage or release of toxins from the necrotic liver. PMID- 1918881 TI - Liver transplantation in HBs antigen (HBsAg) carriers. Prevention of hepatitis B virus (HBV) recurrence by passive immunization. AB - Liver transplantation in HBs-antigen (HBsAg) positive allograft recipients is associated with a high risk of HBV recurrence some time after surgery. So far, results of measures to prevent recurrent HBV-infection by means of treatment with interferon, hepatitis B vaccination and short-term passive immunization with hepatitis B immunoglobulin (HBIg) or monoclonal antibody to HBsAg (anti-HBs) have been disappointing. In the present study the results of long-term, anti-HBs monitored passive immunization with HBIg is reported. In 23 HBsAg-positive liver transplant recipients an anti-HBs level of greater than or equal to 100 IU/l was maintained for 6 or 12 months, respectively. The rate of recurrent infection was found to be less than 20% under HBIg substitution, whereas 11 graft recipients with no or only short-term HBIg prophylaxis were reinfected by month 15 after transplantation. HBV recurrence was associated with chronic liver disease and recurrent cirrhosis in the allograft. PMID- 1918882 TI - Formation of iso-ursodeoxycholic acid during administration of ursodeoxycholic acid in man. AB - The appearance of iso-ursodeoxycholic acid (isoUDCA; 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acid) in serum of patients with chronic cholestatic liver disease and of healthy subjects during administration of ursodeoxycholic acid (UDCA) is reported. Comparison of the mass spectrum of the newly appearing bile acid with that of authentic 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acid revealed its identity as the 3 beta-epimer of UDCA. The appearance of 13C-isoUDCA in serum after ingestion of 13C-UDCA proved its product precursor relationship with UDCA. The putative intermediate in the epimerization of UDCA to isoUDCA, 3 oxo-7 beta-hydroxy-5 beta-cholan-24-oic acid, was identified in serum of patients with cholestatic liver disease during treatment with UDCA. Serum concentrations of isoUDCA after 4 weeks of UDCA treatment were 1.37 +/- 0.79 mumol/l (mean +/- S.D.) in eight patients with primary biliary cirrhosis (PBC), 1.25 +/- 0.91 mumol/l in six patients with primary sclerosing cholangitis (PSC) and 3.87 +/- 0.44 mumol/l in four healthy controls. The intestinal bacterial flora as well as microsomal enzymes of the liver may be involved in the epimerization of UDCA to isoUDCA as indicated by decreased serum levels of isoUDCA under antibiotic treatment with doxycycline (100 mg/day) in healthy subjects and a correlation (r = 0.873, p less than 0.001) between the hepatic microsomal function measured by the 14C-aminopyrine breath test and the fractional conversion of applied UDCA to isoUDCA (isoUDCA/UDCA + isoUDCA) in patients with PBC or PSC. Future studies of bile acid metabolism under UDCA treatment should include measurement of isoUDCA to further elucidate its biological role. PMID- 1918883 TI - Abstracts of the 26th meeting of the European Association for the Study of the Liver. Palma de Mallorca, Spain, 11-14 September 1991. PMID- 1918885 TI - Clinical predictors of infection of central venous catheters used for total parenteral nutrition. PMID- 1918884 TI - Concerns about hospital-based routine human immunodeficiency testing programs. PMID- 1918886 TI - Methicillin-resistant Staphylococcus aureus in nursing homes: putting the problem in perspective. PMID- 1918887 TI - Serial survey of methicillin-resistant Staphylococcus aureus nasal carriage among residents in a nursing home. AB - OBJECTIVE: To study the natural course of nasal colonization by methicillin resistant Staphylococcus aureus (MRSA) among residents in a nursing home. DESIGN: A cohort study with eight surveys of nasal cultures over 15 months. SETTING: A community nursing home in Chicago, Illinois. PARTICIPANTS: Between 117 and 129 residents of the nursing home in each survey. RESULTS: MRSA carriers were present throughout the study period. On the average, 24.4% (range: 17.1% to 34.2%) of the residents carried S aureus, and 35.3% (range: 20% to 62.5%) of the isolates were methicillin resistant at each survey. The carrier state was persistent or transient and was affected little by a roommate's carrier status. Approximately 70% to 80% of residents who were bedridden or who had decubitus ulcers or foreign bodies carried MRSA at least once during the study period. Residents' prior hospitalization was not associated with MRSA carriage. CONCLUSION: This study demonstrated that MRSA was perpetuated in the nursing home by persistently or intermittently colonizing debilitated residents who required more intensive nursing care and that the prior hospitalization of the residents was not an important cause of its perpetuation. PMID- 1918888 TI - Effect of an automated sink on handwashing practices and attitudes in high-risk units. AB - OBJECTIVE: To assess the effects of an automated sink on handwashing practices and attitudes of staff. DESIGN: Quasi-experimental crossover design. SETTING: Two high-risk patient care areas, one postanesthesia recovery room (Site 1), and one neonatal intensive care unit (Site 2) in two tertiary care hospitals. PARTICIPANTS: All patient care staff on study units; approximately 55 individuals. INTERVENTIONS: An automated sink was installed to replace one handwashing sink for about five weeks; the sink was then crossed-over for an equivalent time period to the other location. Handwashing practices of all unit staff were observed in three two-hour observation periods/week. Questionnaires were distributed to staff two weeks after sink installation and at the study's end. RESULTS: One thousand, six hundred ten handwashes were observed. Handwashing practices differed significantly by site. For both sites, hands were washed significantly better but significantly less often with the automated sink (all p less than .001). Staff expressed negative attitudes, however, about certain features of the sink, and these negative attitudes increased over the study period. CONCLUSIONS: Automated devices must be flexible enough to allow adjustments based on staff acceptance. Application of new technology to improve hand hygiene requires a multifaceted approach to behavior change. PMID- 1918889 TI - Clinical significance of neutropenia in patients with human immunodeficiency virus infection. AB - OBJECTIVE: To determine the incidence of infection in human immunodeficiency virus (HIV)-infected patients during periods of neutropenia and non-neutropenia. To compare the infection rates in patients with HIV disease to those in a group hospitalized with neutropenia and hematologic malignancy. DESIGN: Prospective observational study conducted between December 1985 and December 1987 at a university teaching hospital. Thirty patients with documented acquired immunodeficiency syndrome (AIDS) and absolute T-helper cells less than 200 mm/mm3. All patients had a period of non-neutropenia following a neutropenic period (neutrophils less than 1000 cells/mm3). RESULTS: The rate of first infection during neutropenic and non-neutropenic periods for opportunistic infection and nonopportunistic infections were compared. There were no differences between infection rates for the two time periods for both types of infections. A subgroup of patient care days in which non-neutropenic days followed neutropenic days also was studied to eliminate selection bias. In this group, a comparison of infection rates also revealed no difference between neutropenic and non-neutropenic periods. An alternate analysis of the time until first infection during periods of neutropenia or non-neutropenia was done using the Kaplan-Meier product limit method. There was a longer infection-free period for the neutropenic group for opportunistic infections, but it was not statistically significant (p less than .1). In addition, we compared HIV-infected patients with a group of 37 patients with neutropenia from hematologic malignancy. There was a significantly higher rate of all infections, particularly bacteremias (p less than .001), in the group of patients with hematologic malignancies when compared with all subsets of patients with HIV disease. CONCLUSION: We conclude that patients with HIV disease and modest neutropenia do not have an increased risk of bacterial infection. The incidence of all infections is significantly greater in patients with neutropenia secondary to hematologic malignancy. PMID- 1918890 TI - The hospital epidemiologist in long-term care: practical considerations. PMID- 1918891 TI - Expected costs of implementing a mandatory human immunodeficiency virus and hepatitis B virus testing and restriction program for healthcare workers performing invasive procedures. PMID- 1918892 TI - The protectiveness of protective clothing. PMID- 1918893 TI - Bactericidal action of modulated ultraviolet light on six groups of Salmonella. PMID- 1918894 TI - The development of indicators. PMID- 1918896 TI - Automatic washers/disinfectors for flexible endoscopes. PMID- 1918895 TI - Lyme borreliosis. AB - Lyme borreliosis is a complex infectious process that primarily involves the skin, heart, joints, and nervous systems. The infectious agent is the spirochete B burgdorferi, which is transmitted by the Ixodes genus of ticks. The clinical presentations of Lyme disease are protean because of the overlap of stages and varied organ system involvement. Furthermore, as previously mentioned, approximately one-third of Lyme patients are unable to recall a tick bite. Lyme borreliosis should be suspected in anyone with a tick bite. The findings of an EM lesion and flu-like symptoms strongly favor the diagnosis of stage 1 disease. Stage 2 evolves weeks to months after a tick bite, with cardiac and neurological findings as well as musculoskeletal pain. Stage 3 primarily manifests itself as arthritis associated with continuing or additional neurologic complications. Serologic studies are currently the most practical laboratory aid in diagnosis, because almost all infected individuals have a positive antibody response to the spirochete. Treatment with antibiotics usually proves successful, although longer courses of therapy may be needed in later stages of the disease, and some patients may not respond. PMID- 1918897 TI - HIV hospital seroprevalence study guidelines. PMID- 1918898 TI - Healthcare workers and HIV debate goes on. PMID- 1918900 TI - Consultation in nursing: combining different kinds of expertise. PMID- 1918899 TI - Preventive efforts may reduce neonatal group B streptococcus. PMID- 1918901 TI - Meeting the needs of visitors--a practical approach. AB - Large amounts of research have been carried out into the needs of visitors to intensive therapy units and these needs are now well established. These needs may be categorised as emotional, personal and cognitive. What is now required is a quick and easy means by which individual intensive care units can judge their success (or failure) in meeting these needs and a knowledge of strategies to deal with any failures. This paper addresses these issues. Firstly, reasons why nurses should meet visitor needs are listed, secondly these needs are described and thirdly a study by the author is discussed. This study describes a simple yes/no questionnaire approach which may be used to assess the success with which needs are met. A study of the type described here is within the scope of any intensive care unit. Finally, these needs are examined in detail and methods by which these needs may be met are described. PMID- 1918902 TI - A musical road to recovery: music in intensive care. AB - The aim in this paper is to review the possible beneficial effects of music on intensive care patients. Many aspects are considered incorporating the history and physiological and psychological effects music may have. This is then related to the nurses' role within intensive care situations. PMID- 1918903 TI - Swedish emergency hospitals' readiness for disaster; incidence, interest and training. AB - Disasters in Sweden are normally caused by human factors and these are dependent on the development of the community. The readiness of Swedish emergency hospitals to cope with disaster was investigated both in relation to real disasters and training with hospital disaster plans. An inquiry to the chief physician at every emergency hospital in Sweden, aiming to map the incidence of disasters and the availability of relevant further education, showed a low use of disaster plans in practice and little training in the use of them. It is necessary for several departments to take more responsibility for the disaster plans at emergency hospitals, through regular updating of disaster plans and training. This would minimise the number of people with injuries of both somatic and psychiatric origin in real disaster situations. It would be possible to maintain the readiness of Swedish hospitals to cope with disaster by developing a disaster medicine discipline and introducing selected teams of specialised staff at the emergency hospitals. These efforts together would maintain readiness to cope with disaster and stimulate interest in research, education and further education in the field of disaster medicine. PMID- 1918904 TI - A study of nurse-patient interaction in a high dependency unit. AB - Interaction between patients and nurses has for many years been recognised as a crucial part of the process of nursing. Whilst research has been performed into the interactions of individuals within intensive care units and in surgical wards, little work has been done on the intermediate of these two areas: the high dependency unit. This research uses a grounded approach to qualitative research and introduces the beginnings of a model framework for interaction within the area. PMID- 1918905 TI - A review of communication with intubated patients and those with tracheostomies within an intensive care environment. AB - A major aspect of nursing care within intensive care environments is communication. If nursing communication with patients is to be both effective and therapeutic nurses need to understand the principles of communication and identify the purposes of nurse-patient interactions. The main purpose of this article is to review and examine normal communication channels and the actual and potential barriers to communication between nurses and patients who are intubated or have tracheostomies. The assessment of these patients' needs for communication, planning, implementation and evaluation of nursing to meet them are discussed, and also implications for the future. PMID- 1918906 TI - Factors in the diagnostic delays of small bowel malignancy. AB - The overall survival from primary malignancies of the small intestine has not changed over more than four decades. This generally is ascribed to delays in establishing the diagnosis and the advanced stage of the disease when treatment is begun. There has been no critical analysis of these delays. To answer these questions, we reviewed the records of all patients diagnosed with small bowel malignancy from 1967 to 1988 at the Methodist Hospital of Indiana. The onset and duration of symptoms, first medical consultation, time of performance of diagnostic procedures and surgery were verified in 77 patients with histologically confirmed small bowel malignancies. The longest delay occurs from the time medical help is sought to the time the diagnosis is made, not from the onset of symptoms to the first medical consultation. The small bowel should always be considered as a source of unexplained, persistent subtle abdominal symptoms. PMID- 1918907 TI - Barium enema use in Indiana. AB - All 118 hospital-based radiology departments in Indiana responded to a survey of barium enema (BE) use. The percentage of community hospitals in Indiana using barium enema, both single contrast (SCBE) and double contrast (DCBE) for various indications, was similar to that reported for major medical centers around the world. The use of SCBE and DCBE did not differ between small and large hospitals or between hospitals in small versus large communities. There was, however, wide variation among community hospitals in their overall use of either contrast technique. Barium enema usually was performed without antecedent sigmoidoscopy. However, 60% of Indiana hospitals perform BE on the same day as flexible sigmoidoscopy. The results indicate that the use of BE in community hospitals in Indiana is similar to that reported for major medical centers. Like major medical centers, there is no consensus regarding many issues in the performance of BE. PMID- 1918908 TI - Occupational health history: an often neglected part of medical education. AB - The importance of the medical history is well-known to practitioners. In contrast, most practitioners are ill-prepared to associate occupational exposures to physical and chemical agents with illness. Most medical schools have minimal education concerning the occupational and environmental factors related to diseases. This report will guide the practitioner in the link between occupation and illness and will define appropriate resource materials. PMID- 1918909 TI - Woman with right upper quadrant pain. PMID- 1918910 TI - Radial tunnel syndrome. PMID- 1918911 TI - Informed consent: talk to your patients ... or talk to your attorney. PMID- 1918912 TI - "Dr. Svengali, I presume?" Some key clinical uses of hypnosis. PMID- 1918913 TI - Urine drug screens. PMID- 1918914 TI - From the museum. PMID- 1918915 TI - Clinical use of interleukin-2 in treating cancer. PMID- 1918916 TI - Treatment of sensorineural hearing loss. AB - Of the 25 million people who are hearing impaired, 85% suffer from sensorineural hearing loss (SNL). In the past decade, the identification and treatment of SNL have evolved from futile efforts to active intervention. This paper identifies nine forms of inner ear disorders causing SNL for which medical/surgical treatment is available. Physicians must realize that, with appropriate diagnosis and treatment, hearing nerve loss can have a satisfactory outcome. PMID- 1918917 TI - Immunization status of 2-year-olds in a prepaid health care system. AB - The immunization compliance among 2-year-olds in a prepaid healthcare system in Indianapolis was studied. Since appointments and immunizations are covered benefits, immunization rates should approach 100%; complete immunizations were found in only 72%. Problems identified included transient membership, failure to determine immunization status on patients, reluctance to administer immunizations to children with mild illnesses, asking patients to return for administration of immunizations without a physician exam and record-keeping errors. PMID- 1918918 TI - New program enables physicians to provide care to HIV patients. PMID- 1918919 TI - Fetanyl--cocaine of the '90s? PMID- 1918920 TI - "No uncommon disease": neonatal tetanus, slave infants, and the southern medical profession. PMID- 1918921 TI - On the origins of the science in Arrowsmith: Paul de Kruif, Felix d'Herelle, and phage. PMID- 1918922 TI - Cotton Mather, the "angelical ministry," and inoculation. PMID- 1918923 TI - Comments on "The historical decline of tuberculosis in Europe and America: its causes and significance" by Leonard G. Wilson. PMID- 1918924 TI - Neuronal protein NP185 in avian and murine cerebellum: expression during development and evidence for its presence in nerve endings. AB - The neuronal protein NP185 is a neural tissue-specific protein isolated from clathrin-coated vesicles in brain. Using 8G8, a monoclonal antibody (MAb) characterized in our laboratory, we studied the expression and distribution of neuronal protein NP185 in developing avian cerebellum and in mature murine cerebellum. Furthermore, we compared these parameters to that of synapse-specific neuronal protein, synaptophysin, and an axon-specific (i.e., non-synaptic) neuronal protein, neurofilament NF68. We found that NP185 expression temporally and spatially corresponds to avian cerebellar synaptogenesis. In addition, NP185 distribution parallels synaptophysin distribution throughout development, while differing from that of either unassembled or filamentous forms of NF68. The evidence also suggests that embryonic NP185 expression coincides with synaptogenesis, and that NP185 remains concentrated in the terminal boutons of mature neurons. The synapse specificity of NP185 and the recent biochemical properties reported for this protein support the postulate that this molecule may trigger synaptic events and distinguish structurally and functionally active synapses. PMID- 1918925 TI - Histochemical organization and cellular composition of ductal buds in developing human breast: evidence of cytochemical intermediates between epithelial and myoepithelial cells. AB - In developing human breast, terminal end buds (TEBs), lateral buds (LBs), and lobules of three to five alveolar buds (ABs) predominate in prepubertal females, whereas lobules of ABs and lobules of up to 60 ductules predominate in pubertal females. The appearance of clefts in TEBs and LBs suggests that they are precursors of ABs. In histological sections the ductal buds are composed of a heterogeneous collection of cells that include cortical and peripheral cells. The cortical cells can line small lumina in TEBs/LBs, whereas the peripheral cells which cap their distal tips are more irregular and loosely packed. Monoclonal antibodies (MAb) to epithelial milk-fat globule membranes and antiserum to epithelial membrane antigen immunocytochemically stain the cortical cells, particularly where such cells line lumina, and weakly stain the peripheral cap cells. Similar histochemical staining patterns are observed in desialylated sections with peanut lectin. Antiserum and MAb to smooth muscle actin moderately stain the peripheral cap cells, and this staining increases the closer the peripheral cells become to the myoepithelial cells of the subtending duct. Similar but weaker staining patterns are observed with antibodies to vimentin. Keratin MAb PKK2 and LP34, which stain myoepithelial cells in preference to epithelial cells in main ducts, as well as MAb to epithelium-specific keratin 18, all stain many of the cortical/luminal cells in buds and lobules of developing breast; the peripheral cap cells are relatively unstained. It is suggested that the undifferentiated peripheral cap cells show transitional forms both to the cortical epithelial cells that eventually line the lumina and to the myoepithelial cells of the subtending duct. PMID- 1918926 TI - Three-dimensional electron microscopy of ribosomal chromatin in two higher plants: a cytochemical, immunocytochemical, and in situ hybridization approach. AB - We report the 3-D arrangement of DNA within the nucleolar subcomponents from two evolutionary distant higher plants, Zea mays and Sinapis alba. These species are particularly convenient to study the spatial organization of plant intranucleolar DNA, since their nucleoli have been previously reconstructed in 3-D from serial ultra-thin sections. We used the osmium ammine-B complex (a specific DNA stain) on thick sections of Lowicryl-embedded root fragments. Immunocytochemical techniques using anti-DNA antibodies and rDNA/rDNA in situ hybridization were also applied on ultra-thin sections. We showed on tilted images that the OA-B stains DNA throughout the whole thickness of the section. In addition, very low quantities of cytoplasmic DNA were stained by this complex, which is now the best DNA stain used in electron microscopy. Within the nucleoli the DNA was localized in the fibrillar centers, where large clumps of dense chromatin were also visible. In the two plant species intranucleolar chromatin forms a complex network with strands partially linked to chromosomal nucleolar-organizing regions identified by in situ hybridization. This study describes for the first time the spatial arrangement of the intranucleolar chromatin in nucleoli of higher plants using high-resolution techniques. PMID- 1918927 TI - Subcellular localization of secretogranin II and synaptophysin by immunoelectron microscopy in differentiated hypothalamic neurons in culture. AB - Secretogranin II (SgII), a tyrosine-sulfated secretory protein, is a widespread component of endocrine and neuronal cells. In the present study we used mouse hypothalamic neurons differentiated in culture and studied the subcellular localization of SgII by two methods, i.e., by the use of immunoperoxidase or immunogold electron microscopy. By immunoperoxidase labeling, SgII was mainly detected in the matrix of large dense-core vesicles (LDCVs). In addition, usually in nerve terminals containing LDCVs, peroxidase reaction product was also found in association with the membrane of small synaptic vesicles (SSVs). By immunogold labeling, SgII was detected only in the matrix of LDCVs. We also compared the localization of SgII and synaptophysin (SY), an integral membrane protein of SSVs, by double labeling, using a combination of pre-embedding immunogold and peroxidase techniques for SgII and SY, respectively. In perikarya, SgII-positive LDCVs were observed in the vicinity of the Golgi complex and scattered in the cytoplasm. In contrast, SY labeling was restricted to electron-translucent vesicles and tubular membranes in the Golgi area. Moreover, membrane structures positive for both SgII and SY were not found either in the Golgi zone or in other regions of the cytoplasm. In synaptic boutons, immunolabeling of LDCVs and SSVs with anti-SgII and anti-SY, respectively, was mutually exclusive. In summary, within the limitation of the methods used, our data are consistent with the notion that SgII and SY are segregated from each other on exit from the trans Golgi network, than follow two distinct membrane traffic pathways, and that the presence of SgII on the membrane of some SSVs is due to endocytosis. PMID- 1918928 TI - Extracellular matrix components of the mouse thymus microenvironment: ontogenetic studies and modulation by glucocorticoid hormones. AB - The present investigation was an ontogenetic study on the distribution of extracellular matrix (ECM) components in the thymic microenvironment of C57BL/6 mice (comprising young and old adults and developing embryos) and NZB mice. In addition, we evaluated the in vivo and in vitro influence of hydrocortisone treatment on basement membrane protein production by a thymic epithelial cell line. In young normal animals, Type I collagen was restricted to the interstitial spaces of the capsule and septa, where Type IV collagen, fibronectin, and laminin could be detected in the basement membranes. In addition, fibronectin-containing fibers were seen within the medulla of the thymic lobules. The ECM distribution pattern in the developing embryos was distinct from that observed in adults, since a fine meshwork of basement membrane-containing proteins was clearly seen throughout the parenchyma. Moreover, aging normal and NZB mice exhibited a denser ECM pattern than young adult normal animals. Treatment with hydrocortisone, both in vivo and in vitro, resulted in enhancement of ECM expression, detected in mice as early as 2 hr post injection and lasting for several days. Considering that the fluctuations of ECM expression parallel important events in thymocyte differentiation, we discuss the possibility that the two phenomena may be associated. PMID- 1918929 TI - Antiserum to lucifer yellow: preparation, characterization, and use for immunocytochemical localization of dye-filled retinal neurons. AB - We present a new method for the preparation of antisera to Lucifer Yellow, and these antisera are here shown to be particularly suitable for immunocytochemical localization of multiple dye-injected cells in large pieces of vertebrate retina. The method involves the preparation of covalent conjugates of the VS isomer of Lucifer Yellow with keyhole limpet hemocyanin (KLH) or rabbit serum albumin (RSA), and their use as immunogens in rabbits. Both carrier protein conjugates yielded robust antibody responses. Antiserum to the KLH-LY conjugate contained precipitating antibodies against LY and KLH, although activity to the latter did not interfere with immunocytochemical staining. Rabbit antiserum to the RSA-LY conjugate contained precipitating antibody only against LY. When used for immunocytochemical staining of large retinal pieces containing many LY-filled cells, both antisera yielded well-stained, darkly filled cells similar to those seen with the Golgi technique; even very fine dendritic processes of retinal ganglion cells could be followed for long distances. LY immunocytochemistry provides a useful alternative to photooxidation for the analysis of multiple dye injected cells, especially in whole mounts. This approach may also be useful for immunocytochemical identification of cells filled with LY after tissue fixation. PMID- 1918930 TI - Immunocytochemical detection of 5'-bromodeoxyuridine in fluoro-gold-labeled neurons: a simple technique to combine retrograde axonal tracing and neurogenetic characterization of neurons. AB - To characterize the axonal projections of 5'-bromodeoxyuridine (BrdU)-labeled neurons, we have combined retrograde tracer injection of Fluoro-Gold with the immunocytochemical detection of BrdU. Pregnant mice were labeled with pulses of BrdU at embryonic days E12, E13, E14, or E16. Young adult offspring were perfused with 4% paraformaldehyde 2 days after receiving a Fluoro-Gold injection into the cerebral cortex, thalamus, or hippocampus. Brain sections were processed for immunocytochemical visualization of BrdU using the peroxidase-anti-peroxidase method and a diaminobenzidine-nickel ammonium sulfate (DAB-Ni) reaction, and finally observed on a microscope equipped with brightfield and fluorescence optics. Both BrdU-immunoreactive nuclei and retrogradely labeled Fluoro-Gold positive cells were detected. Double-labeled neurons were recognized by the presence of fluorescent particles in the cytoplasm and a black immunoreactive nucleus. Since both labelings occurred in different cell compartments, Fluoro Gold granules were not obscured by the DAB-Ni precipitate. The method shown here permits a correlation of the neurogenesis of subsets of neurons identified by their BrdU content with the specific target into which such cells project. PMID- 1918931 TI - Synthetic guinea pig insulin B-chain C-terminal decapeptide: a novel immunogen for generating immunocytochemical-grade antisera. AB - Antisera to guinea pig insulin are not commonly available, largely because of the short supply and limited immunogenicity of the intact hormone. To overcome these problems we have employed a novel reagent, synthetic guinea pig insulin B-chain C terminal decapeptide, as a hapten for raising antibodies that react with intact guinea pig insulin. The decapeptide, coupled to bovine serum albumin, was successfully used as an immunogen in rabbits. The resulting anti-serum was employed for immunocytochemical staining of guinea pig insulin in pancreatic sections. The specificity of the staining was verified by both pre-absorption and pre-immune serum controls. The utility of this new antiserum for investigations of guinea pig insulin physiology is discussed. PMID- 1918933 TI - Combination of horseradish peroxidase and lucifer yellow staining for selective labeling of neurons at the electron microscopic level. AB - We have developed a new double labeling method for electron microscopy to characterize selectively two physiologically identified neurons on the same preparation. The stomatogastric nervous system of crustaceans was used to test the distinguishing staining characteristics of the two labels. Neurons were labeled on one side with horseradish peroxidase (HRP) and on the other side with Lucifer yellow (LY). After blue light irradiation of the tissue in the presence of diaminobendizine, the two labeled neurons could be easily observed and discriminated on the same section by the two different reaction products. This simple technique of double labeling is useful in experimental neuroanatomy for the detailed study of synaptic relationships. PMID- 1918932 TI - Simultaneous detection of two messenger RNAs in the central nervous system: a simple two-step in situ hybridization procedure using a combination of radioactive and non-radioactive probes. AB - We present here a method enabling the simultaneous detection of two messenger RNAs in tissue sections by use of a two-step in situ hybridization procedure. Tissue sections were hybridized with a radioactive probe and coated with emulsion. The emulsion was processed for development, fixed, and a second hybridization was performed through the emulsion with a biotinylated probe subsequently revealed with streptavidin-alkaline phosphatase. This procedure allows the detection of two mRNAs without loss of signal, removal of the emulsion, or spurious reaction. The simultaneous detection of oxytocin and vasopressin mRNAs in the hypothalamus, and of dopamine receptor and neuropeptide mRNAs in the striatum, demonstrated the efficiency of the procedure. Such a two step procedure provides a simple and flexible way to make possible comparative analysis of the localization of two mRNAs within the same tissue section. PMID- 1918934 TI - Gold enhancement of gold-labeled probes: gold-intensified staining technique (GIST). AB - In this report we present a staining method in which gold chloride is used to enhance the size of gold colloids. We show the utility of this technique when used in conjunction with small gold colloids, i.e., 5 nm, 4 nm, and 2.6 nm. Post embedding staining of epoxy-embedded, gold-labeled mouse LM fibroblasts showed that staining with 0.1% gold chloride facilitated the visualization of the smallest gold colloids. PMID- 1918935 TI - Lectinocytochemical specificity in human eosinophils and neutrophils: a reexamination. AB - As with secretory granules in other cell types, many of the protein components that make up the cytoplasmic granules of human leukocytes are glycoproteins. It is not unexpected, therefore, that lectins specific for various carbohydrate moieties can be localized in these granules following appropriate protocols for specimen preparation and thin-section labeling. In this study, isolated human eosinophils and neutrophils were prepared for lectin-gold electron microscopic localization by procedures that involve no exposure to aqueous fixatives, buffers, or solvents (rapid cryofixation and molecular distillation drying), thus removing the potential problem of constituent extraction or translocation during so-called "wet chemical" processing. In contrast to other reports, data presented illustrate the specific binding of soybean agglutinin (SBA) to eosinophil granule matrices (not the crystalline cores), as well as to a population of granules in neutrophils. A similar labeling pattern for wheat germ agglutinin (WGA) was also seen, confirming the presence of N-acetyl-D-galactosamine and N-acetyl-D glucosamine residues in eosinophil and neutrophil granule matrices. These studies emphasize the need for carefully designed specimen preparation as well as subsequent thin-section labeling procedures in lectinocytochemical studies. PMID- 1918936 TI - Exact ultrastructural localization of glutathione peroxidase in normal rat hepatocytes: advantages of microwave fixation. AB - Glutathione peroxidase (GSH-PO), a highly soluble, selenium-dependent enzyme metabolizing lipid peroxides, is allegedly distributed in both the cytosol and mitochondria. With the pre-embedding method of immunoelectron microscopy for GSH PO employing conventional immersion-fixation, the nuclei of rat hepatocytes stain positively, whereas mitochondria are negative. Such observations are inconsistent with the results of biochemical and immunoblot analyses using isolated subcellular fractions. In the present study, we employed the combination of microwave irradiation and fixation in 4% paraformaldehyde (PFA), with or without 0.1% glutaraldehyde (GA), to enhance the accuracy of ultrastructural localization of GSH-PO in rat liver. A small block of liver was irradiated by microwave for 10 sec in cold cacodylate-buffered 4% PFA containing 0.1% GA. After further immersion of the tissue in 4% PFA at 4 degrees C for 1-6 hr, the standard procedure for pre-embedding immunoelectron microscopy was employed. We observed partial inhibition of artifactual diffusion of cytosolic GSH-PO into the nuclei and consistent GSH-PO localization in mitochondria. Dual localization of this enzyme in the cytosol and mitochondria of normal rat hepatocytes was thus confirmed. PMID- 1918937 TI - Immunocytochemical localization of cathepsin B in rat anterior pituitary endocrine cells, with special reference to its co-localization with renin and prorenin in gonadotrophs. AB - We examined by immunocytochemistry the localization of cathepsin B in endocrine cells of rat anterior pituitary lobe, using a monospecific antibody to cathepsin B. By light microscopy, granular immunodeposits for cathepsin B were detected in most endocrine cells of anterior pituitary lobe. Cells immunoreactive for luteinizing hormone (LH) were diffusely immunostained by anti-cathepsin B. By electron microscopy, immunogold particles for cathepsin B were localized in lysosomes of thyrotrophs, somatotrophs, and mammotrophs. In mammotrophs, immunogold particles for cathepsin B were also detected in crinophagic bodies. Double immunostaining co-localized immunogold particles for LH and cathepsin B in secretory granules of gonadotrophs. Immunocytochemistry was also applied to demonstrate localization of renin and prorenin in LH-producing gonadotrophs; immunogold particles for renin were co-localized with those for LH, cathepsin B, or prorenin in their secretory granules. Immunogold particles for prorenin were also co-localized with those for LH or cathepsin B in secretory granules, but prorenin-positive granules appeared less frequently than renin-positive granules. These results suggest that cathepsin B not only plays a role in the protein degradation in lysosomes of anterior pituitary endocrine cells but also participates in the activation of renin in gonadotrophs, as has been demonstrated in secretory granules of juxtaglomerular cells. PMID- 1918938 TI - Ultrastructural localization of adenylate cyclase activity in chicken osteoclasts. AB - Using lead citrate as a capture reagent and adenylate-(beta, gamma-methylene) diphosphate (AMP-PCP) as a substrate, we localized adenylate cyclase activity on the non-ruffled border plasma membrane of approximately half of the osteoclasts on trabecular bone surfaces in the tibial metaphyses of chickens fed a low (0.3%) calcium diet. The enzyme was not detectable in osteoclasts when chickens were fed a normal calcium diet. Activity was observed on the entire plasma membrane of detached osteoclasts that were situated between osteoblasts on the bone surface and blood vessels in the marrow cavity. Detection of activity on detached osteoclasts required the presence of an activator, implying lower levels in these cells than in those with ruffled borders. Staining was greater on the lateral sides of osteoblasts and osteoclasts when they were in contact with each other. Reaction specificity was indicated by the demonstration of stimulation by forskolin, guanylate-(beta, gamma-methylene) diphosphate (GMP-PCP), dimethylsulfoxide, and NaF, inhibition by alloxan and 2',5'-dideoxyadenosine, and absence of activity when sections were incubated in substrate-free medium or when GMP-PCP replaced AMP-PCP as a substrate. The finding of adenylate cyclase in osteoclast plasma membrane provides structural evidence that the adenylate cyclase-cyclic AMP system has a role in regulation of osteoclast cell function. The low-calcium diet appears to have resulted in increased amounts of adenylate cyclase in osteoclasts. PMID- 1918939 TI - Monoclonal antibodies to type V collagen for immunohistological examination of new tissue deposition associated with biomaterial implants. AB - We developed a panel of highly specific monoclonal antibodies (MAb) against dog Type V collagen. Each antibody showed differential reactivities towards Type V collagen from other species. All the antibodies were highly reactive in conventional ELISA, as well as with electroblots of collagen after polyacrylamide gel electrophoresis using non-denaturing conditions. The MAb were shown to be suitable for the immunohistological detection of Type V collagen in tissue sections, although this normally required pre-treatment of sections with 50 mM acetic acid. In particular, the antibodies were shown to be useful for examining samples of a collagen-based biomaterial, a vascular prosthesis, after explant from evaluation in an animal model. This showed that Type V collagen was most prominent in regions of new tissue formation within the neointima, close to the inner surface of the prosthesis. The broad spectrum of differential reactivities allows the antibodies to be used for a wide range of experimental models. These MAb therefore provide a novel approach for the evaluation of biomaterial performance, particularly for collagen-based implants. PMID- 1918940 TI - Immunohistochemical localization of Zn-alpha 2-glycoprotein in normal human tissues. AB - The Zn-alpha 2-glycoprotein (Zn-alpha 2-GP) is present at a high concentration in the seminal plasma and at significant levels in other human body fluids. Its precise localization, however, has remained unclear, as well as its physiological and pathological significance. The present study reports the immunohistochemical localization of this protein in normal adult human tissues. Localization of the reactive product to anti-human plasma Zn-alpha 2-GP antibody was demonstrated in the following cells: luminal and basal cells of the prostate gland, luminal epithelial cells of the acini and of some ducts of the mammary glands, luminal cells of the secretory portion of the eccrine and apocrine sweat glands, serous cells of the salivary, tracheal, and bronchial glands, acinar cells of the esophageal glands, exocrine acinar cells of the pancreas, hepatocytes of the liver, and epithelial cells of the proximal and distal tubules in the kidney. The present results suggest that Zn-alpha 2-GP exerts some unknown but fairly widespread exocrine function and may be produced in the various epithelial cells tested. Hepatocytes are also suggested to be a source of the protein in the blood plasma. PMID- 1918941 TI - Partition of epidermal growth factor receptors on freeze-fractured plasma membranes of A431 cells is affected by the ligand. AB - The fracture immunolabel technique, which permits assessment of the partition of transmembrane proteins with the inner or outer leaflets of the freeze-fractured membrane, was used to analyze the behavior on fracture of epidermal growth factor (EGF) receptors over the plasma membranes of A431 cells. The receptors partition mainly with the outer leaflet of the freeze-fractured plasma membranes, whereas they become associated with the inner leaflet when they are occupied by the ligand. This modified partition is even more evident after receptor clustering induced by incubation with EGF at 37 degrees C. Treatment with 12-O tetradecanoylphorbol-13-acetate (TPA) decreases the number of receptors over both inner and outer leaflets. An effect similar to that induced by the ligand is obtained when receptor aggregation is achieved using anti-receptor monoclonal antibodies (MAb). The modified partition therefore indicates receptor activation and appears to be a consequence of receptor cross-linking rather than to reflect a conformational change of the receptor molecule. Parallel immunolabeling with anti-phosphotyrosine antibodies of freeze-fractured EGF-treated A431 cells reveals that the receptors, when activated, are associated only with the inner leaflet of the plasma membrane. PMID- 1918942 TI - Effects of different fixatives on detection of nucleic acids from paraffin embedded tissues by in situ hybridization using oligonucleotide probes. AB - Detection of nucleic acids from paraffin-embedded material by in situ hybridization with oligonucleotide probes is increasingly being used. To determine the effect of fixation on the preservation of DNA and mRNA, we studied 18 lymphoid tissues fixed in B5, formalin, OmniFix, ethanol, and Bouin's fixatives and embedded in paraffin by in situ hybridization, using biotinylated oligonucleotide poly d(T) probes and immunoglobulin light chain probes. Detection of DNA using the poly d(T) probe was most consistent and most intense in tissue fixed in formalin, followed by OmniFix and ethanol, with B5 and Bouin's fixatives yielding unsatisfactory results. Detection of mRNA, using the light chain probes, was most consistent and most intense with tissue fixed in formalin and Bouin's solution, followed by B5 fixative, with OmniFix and ethanol fixatives yielding unsatisfactory results. The results of mRNA detection using the poly d(T) probe were found not to correlate with mRNA content as determined by the light chain probes for several fixatives, possibly owing to selective degradation of portions of the mRNA molecule. PMID- 1918943 TI - Heparin binding lectin of human placenta as a tool for histochemical ligand localization and isolation. AB - Biotinylated heparin has been used to detect the presence of specific binding sites in sections of human placenta, which has prompted demonstration of expression of lectin activity for this proteoglycan. Purification of this lectin from full-term placenta facilitates the synthesis of its biotinylated derivative, using biotin-amidocaproyl hydrazide, without affecting its activity. It also enables immunization to obtain antibodies. The labeled lectin is shown to bind specifically to nuclear and cytoplasmic locations in various cell types of human placenta, nuclear expression of lectin binding sites being more pronounced at the full-term stage than after 8 weeks of development. The structurally related histone H2B exhibits obvious differences in its binding pattern. The presence of ligands accessible to the lectin whose binding activity can be inhibited by addition of an excess of heparin correlates in most instances with the level of lectin expression detected immunohistochemically. Biochemical information on the nature of the glycohistochemically inferred lectin-specific ligand(s) is obtained by affinity chromatography on resin-immobilized lectin. It leads to isolation of a proteoglycan with similar electrophoretic mobility in agarose-polyacrylamide gel electrophoresis relative to the independently purified heparan sulfate containing fibronectin binding proteoglycan from human placenta. Both fractions inhibit binding of heparin to the lectin and contain immunologically detected co purified lectin, emphasizing their ligand properties. Application of labeled tissue lectins in conjunction with lectin-specific antibodies is proposed to obtain valuable insights into the expression of the receptor as well as the ligand part of protein-carbohydrate recognition. PMID- 1918944 TI - Generation of lobuloalveolar development from isolated rat mammary ducts and end buds. AB - Implantation of excised bud-free ductal fragments (DUCTS), terminal end buds (TEBs), or alveolar buds (ABs) from virgin mammary glands of Wistar-Furth rats into interscapular fat pads of syngeneic female rats produces, after 16 weeks, complete ductal outgrowths including TEBs and ABs. Treatment of the recipient rats with perphenazine for 1 day or mating them after 12 weeks and then isolating the resultant outgrowths after 16 weeks produces significantly larger outgrowths than those from untreated hosts. The outgrowths consist of distended ducts and lobules or distended ducts and alveoli, respectively. Histochemical and immunocytochemical staining of the outgrowths with reagents that depict epithelial, myoepithelial, and lactating alveolar cells (peanut lectin alone, monoclonal and polyclonal antibodies to rat caseins) indicate similar cell compositions and arrangements for all outgrowths irrespective of their source; these are also similar to the mammary glands of the perphenazine-stimulated or lactating hosts. There is one major difference: the degree of staining of peanut lectin alone and the anti-caseins is greater for outgrowths produced by the ABs and TEBs than for those produced by the DUCTs. DUCT implants left for 1 year after cessation of lactation of the hosts are still stained appreciably by peanut lectin alone and by the anti-caseins, particularly the luminal secretions. Therefore, the complete morphogenetic and cell differentiating ability for generating mammary glands is present in bud-free ducts, but this ability can be enhanced in TEBs/ABs or abnormally expressed at ectopic sites. PMID- 1918945 TI - Novel applications of acrylamide for cryosectioning of isolated cells, tissues, and arthropods. AB - Cross-linked and uncross-linked acrylamide polymers were used to alleviate technical difficulties in cryosectioning and autoradiographic processing of marine arthropods (Pycnogonum litorale), larval insect tissues (Sarcophaga bullata), and amphibian (Xenopus laevis) oocytes. Rapidly polymerized cross linked acrylamide was used to prepare sections from an animal with a hard thick cuticle, P. litorale. Fragmentation and compression artifacts caused by tissue density differences were avoided and internal tissues were well preserved. Our results indicate that closely applied external support eliminates difficulties typically associated with arthropod cryosectioning. Pre-polymerized, uncross linked acrylamide provided similar protection when used for sectioning larval tissue from S. bullata. Soft tissues under the cuticle were undamaged in tracheal and epidermal preparations. This polymer was also an excellent embedding material for soft tissues such as salivary glands, quickly penetrating tissue cavities and eliminating air bubbles. Uncross-linked acrylamide was used as an embedding and culturing medium for oocytes from X. laevis. The polymers were non-toxic and allowed the preparation of thin frozen sections containing as many as 50 large oocytes per section. PMID- 1918946 TI - Murine endothelioma cell lines transformed by polyoma middle T oncogene as target for and producers of cytokines. AB - We studied cytokine-related functional properties of four mouse endotheliomas from different anatomical sites obtained by transformation with middle T oncogene. We examined mRNA expression of IL-6, IL-1 alpha, macrophage-CSF, granulocyte/macrophage-CSF, and two members of an emerging super-family of chemotactic cytokines (JE/monocyte chemoattractant protein-1 (MCP-1) and KC). Exposure to IL-1 augmented or induced cytokine gene transcripts in three endothelioma lines (eEnd.1, sEnd.1, and tEnd) with maximal expression in tEnd.1 cells. Endothelioma cells also responded to TNF-alpha and LPS. Levels of IL-6 and monocyte chemotactic activity (a JE/MCP activity) correlated with mRNA expression. IL-1 also induced production of procoagulant activity and platelet activating factor in endothelioma cells, with heterogeneity in the levels of response among individuals lines. Murine melanoma B16-F1, human colon carcinoma HT29 cells, CB33MT lymphoblastoid cells, and monocytes adhered to endothelioma monolayers and the adhesive properties of these cell lines were modulated by IL-1 beta, with marked differences among themselves. Murine EC derived from brain capillaries, used as control, shared several properties with bEnd.4 line. Endothelioma lines cause tumors by recruiting host cells. The capacity to produce cytokines that directly or indirectly attract host vascular cells, may play an important role in hemangioma induction in vivo. Murine endothelioma lines, generated by transformation with the polyoma middle T oncogene, retain functional properties of normal endothelium, and may represent an invaluable tool for analysis of the immunobiology and heterogeneity of EC in different tissues. PMID- 1918947 TI - Humoral recall responses in HIV infection. Levels, specificity, and affinity of antigen-specific IgG. AB - To evaluate the integrity of humoral immunologic memory among persons with HIV infection, we measured the levels, specificity, and functional affinity of circulating antibodies to vaccine-related recall Ag, tetanus (TT) and diphtheria toxoids (DT), and to naturally acquired measles virus, in sera from 17 HIV seronegative control subjects, 17 asymptomatic HIV-seropositive patients, and 10 patients with AIDS. Preimmunization levels of TT- and measles-specific IgG were similar in all groups, although DT-specific IgG was lower in AIDS patients. Four wk after immunization with TT3 and DT, all groups showed significantly increased specific antibody levels (p less than 0.02). The asymptomatic HIV+ patients and control subjects achieved similar peak serum levels of TT-specific IgG (102 +/- 32 and 169 +/- 36 micrograms/ml, respectively). In contrast, the AIDS patients had lower peak values of both TT- and DT- specific IgG (p less than 0.05). Peak levels correlated directly with the number of CD4+ T cells (p less than 0.05). However, 80 to 100% of all participants tested, independent of HIV status, showed higher levels of TT- and DT-specific IgG 6 mo after immunization compared with preimmunization levels. The antitoxoid antibodies were specific as they did not cross-react with other Ag in competitive inhibition experiments. In addition, all groups exhibited antibodies to TT and DT both pre- and postimmunization of equivalent functional affinity (avidity) (Kd = 10(-10)-10(-11) mol/liter). We conclude that, in contrast to the profoundly depressed humoral responses to new Ag, persons with asymptomatic HIV infection retain humoral immunity to certain recall Ag. These levels of specific IgG to three recall Ag are not proportional to elevated levels of total serum IgG in HIV-infected patients. In addition, many patients with HIV respond to challenge with recall Ag by producing significant amounts of high affinity IgG that may persist over time. PMID- 1918948 TI - Evaluation of monophosphoryl lipid A (MPL) as an adjuvant. Enhancement of the serum antibody response in mice to polysaccharide-protein conjugates by concurrent injection with MPL. AB - Concurrent injection of monophosphoryl lipid A (MPL) in saline or as an oil-in water emulsion enhanced both the primary and secondary serum antibody responses to the capsular polysaccharide (CP) components of seven conjugates: the enhanced responses were Ag-specific. In contrast, MPL did not enhance the serum antibody response to five of the six unconjugated CP. MPL and trehalose dimycolate injected concurrently with the unconjugated Vi CP of Salmonella typhi (Vi) enhanced the serum antibody response to that Ag. MPL further enhanced the Vi antibody levels when injected with conjugates of this CP. The serum antibody responses to Pseudomonas aeruginosa exotoxin A, used as the carrier protein for the Staphylococcus aureus types 5 and 8 conjugates, were also enhanced by MPL. MPL in oil-in-water emulsion was generally more effective than when administered in saline. PMID- 1918949 TI - Myosin-induced acute myocarditis is a T cell-mediated disease. AB - The heart is a target organ in several autoimmune diseases, and therefore it is important to understand more about the effector cells involved in immune-mediated mechanisms of myocardial cell death. Because immune T lymphocytes are central to many immune responses, we wanted to study the role of T cells in causing cardiac specific inflammation. We used purified mouse cardiac myosin to cause acute myocarditis in mice. The adoptive transfer of purified T cells from C.B-17 mice with active myocarditis to SCID recipients successfully transferred the disease into SCID hosts. In contrast, transfer of serum with high-titer antimyosin antibodies to SCID hosts did not cause myocarditis. Using mAb to deplete A/J mice of CD4+ T cells, we showed that these mice were protected against the induction of myocarditis. Depletion of CD8+ T cells reduced the severity of inflammation but did not prevent induction of myocarditis. We were also able to prevent the induction of myocarditis using major histocompatibility class II protein-binding, nonimmunogenic, competitor peptides. These blocking studies also indicated that in H-2k mice, myocarditis is an I-Ak-restricted disease, and provided further evidence that CD4+ T cells are critical to the induction of disease. Together, these studies provide direct evidence that myosin-induced myocarditis is a T cell mediated disease. PMID- 1918950 TI - Long-term xenogeneic chimeras. Full differentiation of rat T and B cells in SCID mice. AB - To test whether T and B cell differentiation can proceed across species barriers, rat fetal liver (FL) cells were used to reconstitute SCID mice. Provided that the hosts were conditioned with light irradiation, i.v. injection of FL cells caused near-complete repopulation with rat-derived lymphohematopoietic cells, including myeloid and erythroid cells, Ia+ cells of the macrophage/dendritic cell lineages, and mature T and B cells. In keeping with the known hypersensitivity of SCID cells to irradiation, host hematopoietic cells in the chimeras were almost undetectable, even with hosts exposed to as low as 250 rad. In the case of T cells, the distribution of immature and mature cells in the thymus of rat FL--- SCID chimeras closely resembled the normal rat thymus in terms of architecture and expression of CD4, CD8, and alpha beta-TCR molecules. Thymopoiesis was followed by the appearance of large numbers of typical rat CD4+ and CD8+ cells in spleen and lymph nodes. These organs also contained substantial numbers of rat B (mu+) cells. The data thus indicate that the xenogeneic environment of SCID mice is fully capable of sustained de novo differentiation of rat T and B cells. PMID- 1918951 TI - Acylation of cell-associated IL-1 by palmitic acid. AB - To determine whether membrane-associated IL-1 is palmitylated, we labeled LPS activated human monocytes with [3H]palmitic acid. The plasma membranes were isolated, and the membrane proteins extracted and analyzed simultaneously by SDS PAGE-autoradiography and Western blot analysis from the same gel. When the monocytes were labeled with [3H]palmitate, 23- and 31-kDa bands were visualized, for membrane-associated IL-1 and its precursor, respectively. The 31- and 23-kDa bands were excised from several gels and rehydrated and analyzed again by SDS PAGE, autoradiography, and Western blot analysis. The 23- and 31-kDa bands appeared again by both methods. To further investigate membrane-associated IL-1 acylation, human monocytes were labeled with [3H]palmitate, the plasma membranes isolated, and the membrane proteins extracted by CHAPS detergent. Immunoprecipitation of isolated membrane proteins using anti-IL-1 antibodies revealed two bands of 23 and 31 kDa after autoradiography. The studies demonstrate that both membrane-associated IL-1 and the IL-1 precursor are acylated with palmitic acid. PMID- 1918953 TI - Regulation of IL-6 expression by oncostatin M. AB - Endothelial cells produce immunomodulatory cytokines in response to soluble mediators of inflammatory/immune reactions. We have previously demonstrated that the leukocyte-derived cytokine, oncostatin M (Onco M) can alter endothelial cell morphology, regeneration, and fibrinolytic activity in vitro. Here we demonstrate that Onco M stimulates the production of the pleiotropic cytokine, IL-6, in cultured human endothelial cells (HEC) in a time- and dose-dependent manner. Specific antibodies to IL-6 neutralize the growth-inhibitory activity for human breast carcinoma cells that is secreted by HEC in response to Onco M treatment. Specific immunoassays indicate greater than 10-fold increases in the IL-6 content of culture supernatants as early as 6 h post-treatment with Onco M (ED50 = 17 pM). This stimulation of IL-6 production by Onco M is associated with a sevenfold increase in intracellular levels of IL-6 mRNA. IL-1 alpha and TNF-alpha are also potent inducers of IL-6 production in these cells, the order of potency being IL 1 alpha greater than Onco M greater than TNF-alpha. TNF-alpha, but not IL-1 alpha, synergizes with Onco M to augment IL-6 production in HEC. HEC are 10 to 20 times more responsive to Onco M than are other nonendothelial cell types. In addition, HEC express 10 to 20 times greater numbers of high affinity cell surface receptors for Onco M than do other nonendothelial cell types. Based on these findings, we propose that Onco M may represent a new immunomodulator regulating cytokine-induced gene products in endothelial cells. PMID- 1918952 TI - Human eosinophil cytotoxicity-enhancing factor. II. Multiple forms synthesized by U937 cells and their relationship to thioredoxin/adult T cell leukemia-derived factor. AB - Recently, our laboratory reported the purification and partial amino acid sequence of a 10-kDa eosinophil cytotoxicity-enhancing factor (ECEF) polypeptide from the U937 cell source. This cytokine enhanced human eosinophil antibody dependent cytotoxic function by greater than 200% and was half-maximally effective at a concentration of approximately 1 ng/ml. In this study, we describe the conditions required for ECEF synthesis and the use of rabbit antibody raised to 10-kDa ECEF to investigate the existence of related polypeptide species. Unstimulated U937 cells released an immunoreactive 14-kDA species. Cells stimulated with 7.5 micrograms/ml of LPS also released a 13-kDa species. Cells stimulated with 400 ng/ml of PMA also synthesized a 10-kDa species (equivalent in size to the form we had purified). This 10-kDa species remained primarily cell associated, but detectable amounts were released into the supernatant by 48 h of culture. In washed cell pellets, the location of the 10-kDa species was found to be in the plasma membrane, externally oriented, as determined by FACS analysis, iodination with the membrane impermeable reagent 125I-sulfosuccinimidyl-3-(4 hydroxyphenyl) propionate, and by its removal with brief trypsin treatment. Partial amino acid sequence data suggested that the 14-, 13-, and 10-kDa species all share the same N-terminal. The 14- and 10-kDa ECEF species were recovered by electroelution from SDS-PAGE gels and tested for activity in the assay of eosinophil cytotoxic function. Because of the amino acid sequence similarities between the ECEF species and thioredoxin (TRX), rTRX (synthesized in Escherichia coli and purified) was also tested for activity. The 14-kDa ECEF and rTRX induced a slight, but consistent and statistically significant enhancement of eosinophil cytotoxic function. By comparison, lower doses of the 10-kDa ECEF induced a major increase in cytotoxic function. Thus the forms of ECEF differ in size, conditions required for synthesis, trafficking by the U937 cell after synthesis, and biologic activity. It is likely that these considerations bear on the involvement of ECEF in the pathophysiology of eosinophilia in vivo. PMID- 1918954 TI - Release of IL-1 from mononuclear phagocytes. AB - IL-1 alpha and -beta are 31- and 34-kDa cytokines produced by stimulated monocytes, macrophages, and a variety of other cells. These proteins are thought to function primarily as intercellular mediators and can be detected in plasma and the supernatants of cultured cells; however, IL-1 alpha and -beta contain no identifiable signal peptides and are not secreted via the classical secretory pathway. To understand the mechanism of IL-1 release, we have analyzed IL-1 production by LPS-stimulated mononuclear cells. IL-1 was quantified by bioassay, immunoprecipitation, and ELISA. Of these techniques, only immunoprecipitation permitted the quantitative detection of intracellular pro-IL-1. Both the full length pro-forms and proteolytically processed mature forms of IL-1 were detected in culture supernatants; however, for macrophages the released material represented less than 5% of the total IL-1 alpha and -beta synthesized. Freshly isolated human monocytes released a higher fraction of their total IL-1 (up to 22%): however, monocytes cultured in vitro for 24 h showed very little fractional release, similar to macrophages. Nonspecific release of intracellular contents was determined by measurement of release of lactate dehydrogenase activity and was found to parallel IL-1 release. In fact the higher release of IL-1 from freshly cultured human monocytes correlated also with an increase in the release of lactate dehydrogenase. We conclude that, in cultured LPS-stimulated monocytic cells, IL-1 is not released via a novel secretory pathway, but exits the cell via a nonspecific pathway, most likely as a consequence of cellular injury. PMID- 1918955 TI - Synovial tissue macrophage as a source of the chemotactic cytokine IL-8. AB - Cells of the synovial microenvironment may recruit neutrophils (PMN) and lymphocytes into synovial fluid, as well as lymphocytes into the synovial tissues, of arthritic patients. We have investigated the production of the chemotactic cytokine IL-8 by using sera, synovial fluid, synovial tissue, and macrophages and fibroblasts isolated from synovial tissues from 75 arthritic patients. IL-8 levels were higher in synovial fluid from rheumatoid (RA) patients (mean +/- SE, 14.37 +/- 5.8 ng/ml), compared with synovial fluid from osteoarthritis patients (0.135 +/- 17 ng/ml) (p less than 0.05) or from patients with other arthritides (5.52 +/- 5.11 ng/ml). IL-8 from RA sera was 8.44 +/- 2.33 ng/ml, compared with nondetectable levels found in normal sera. IL-8 levels from RA sera and synovial fluid were strongly positively correlated (r = 0.96, p less than 0.05). Moreover, RA synovial fluid chemotactic activity for PMN in these fluids was inhibited 40 +/- 5% upon incubation with neutralizing polyclonal antibody to IL-8. Synovial tissue fibroblasts released only small amounts of constitutive IL-8 but could be induced to produce IL-8 by stimulation with either IL-1 beta, TNF-alpha, or LPS. In contrast, unlike normal PBMC or alveolar macrophages, macrophages isolated from RA synovial tissue constitutively expressed both IL-8 mRNA and antigenic IL-8. RA synovial macrophage IL-8 expression was not augmented by incubation with either LPS, TNF-alpha, or IL-1 beta. Immunohistochemical analysis of synovial tissue showed that a greater percentage of RA macrophages than osteoarthritis macrophages reacted with anti-IL 8. Whereas macrophages were the predominant cell for immunolocalization of IL-8, less than 5% of synovial tissue fibroblasts were positive for immunolocalized IL 8. These results suggest that macrophage-derived IL-8 may play an important role in the recruitment of PMN in synovial inflammation associated with RA. PMID- 1918956 TI - Inhibition of IL-8-induced W3/25+ (CD4+) T lymphocyte recruitment into subcutaneous tissues of rats by selective depletion of in vivo neutrophils with a monoclonal antibody. AB - IL-8 recruits both neutrophils and lymphocytes in vitro and in vivo. To elucidate the mechanisms of lymphocyte recruitment in vivo by IL-8, we examined the role of neutrophil infiltration through selective depletion of circulating neutrophils using a mAb, RP-3. Selective depletion of neutrophils inhibited the IL-8 induced in vivo migration of the W3/25+ (CD4+) T cell subset but did not inhibit that of the MRC-OX8+ (CD8+) subset. These results suggest that CD4+ T cell migration into IL-8-injected s.c. tissues depends on the prior infiltration of neutrophils chemoattracted directly by IL-8. PMID- 1918957 TI - The signal transduction pathway involved in the migration induced by a monocyte chemotactic cytokine. AB - Recombinant monocyte-chemotactic and activating factor (rMCAF; alternative acronyms MCP-1, TDCF, human JE) induced migration of human monocytes across polycarbonate or nitrocellulose filters. Maximal induction of migration was observed at a concentration of 10 ng/ml (10(-9) M). Checkerboard analysis revealed that rMCAF elicited true gradient-dependent chemotactic migration, although a gradient independent chemokinetic effect was observed at low concentrations (1-5 ng/ml). rMCAF caused a rapid (less than 5 s) and transient (approximately 1.5 min) increase of free cytosolic Ca2+ ions, as assessed by the fura-2 probe. No Ca2+ increase was detected in neutrophils or lymphocytes stimulated by rMCAF. Studies conducted in the absence of extracellular Ca2+ or in the presence of Ni2+ (an inhibitor of Ca2+ influx) suggested that the increase of intracellular Ca2+ induced by rMCAF is dependent on the influx of extracellular Ca2+ through plasma membrane channels. Bordetella pertussis toxin inhibited the intracellular Ca2+ elevation and chemotaxis caused by rMCAF. The possible involvement of Ca(2+)-dependent protein kinases in rMCAF signaling pathway(s) was explored using inhibitors. Inhibitors of GMP-dependent kinase and myosin L chain kinase had no effect on rMCAF-induced monocyte migration. In contrast, protein kinase C/cAMP-dependent kinase inhibitors (such as, C-I, H-7, HA-1004, KT5720, and Staurosporine) markedly decreased rMCAF induced chemotaxis suggesting the involvement of a serine/threonine protein kinase, possibly protein kinase C, in rMCAF signaling pathway. PMID- 1918959 TI - Production and characterization of mouse monoclonal antibodies against human monocyte chemoattractant protein-1. AB - We developed five different hybridoma cell lines that produced mAb against human monocyte chemoattractant protein-1 (MCP-1). The subclass of all five antibodies was IgG1. All five mAb formed complexes with metabolically labeled MCP-1 that could be demonstrated by immunoprecipitation. The antibodies were specific for MCP-1. They did not cross-react by immunoprecipitation with structurally related host defense cytokines present in metabolically labeled PHA- or LPS-stimulated mononuclear cell culture fluids, nor did they cross-react in a direct ELISA with neutrophil attractant/activation protein-1, with crude platelet lysate proteins, or with pure platelet proteins that have amino acids sequences similar to that of MCP-1. The mAb also reacted with rMCP-1 expressed in Escherichia coli, suggesting that they recognize protein structure rather than the glycosylated portion of human MCP-1. When the mAb were mixed with MCP-1, the monocyte chemotactic response to MCP-1 was inhibited. A sandwich ELISA was developed to detect MCP-1 in biologic fluids containing relatively high concentrations of other proteins. The sensitivity was 300 pg/ml, or 30 pg/ELISA well. An anti-MCP-1 mAb column was used in an improved method of MCP-1 purification. Approximately 240 micrograms of MCP-1 were purified from 5 liters of FCS-containing U-105MG cell culture supernatant. The yield was at least 60%. In addition to two forms of MCP-1 reported previously by us, two more forms of MCP-1 were found in a mixture of culture supernatants of PHA- and LPS-stimulated human PBMC. PMID- 1918958 TI - A novel monoclonal antibody against murine IL-2 receptor beta-chain. Characterization of receptor expression in normal lymphoid cells and EL-4 cells. AB - A mAb specific for the murine IL-2R beta-chain (IL-2R beta) was produced by immunizing a rat with a rat transfectant cell line expressing a large number of cDNA-encoded murine IL-2R beta. The mAb, designated TM-beta 1, is specifically reactive with the murine IL-2R beta cDNA-transfectant but not with the recipient cell, and immunoprecipitates murine IL-2R beta of Mr 75 to 85 kDa. TM-beta 1 mAb completely abolished the high affinity IL-2 binding by inhibiting the ligand binding to IL-2R beta. Murine IL-2R beta was found to be constitutively expressed on a subpopulation of CD8+ T cells and almost all NK1.1+ NK cells in the spleen, whereas TM-beta 1 mAb inhibited the proliferation of spleen cells induced by 1 nM of IL-2. Interestingly, EL-4 cells that express murine IL-2R beta as detected by TM-beta 1 mAb can bind neither human nor murine IL-2 under the intermediate affinity conditions, although cDNA-directed human IL-2R beta expressed in the same EL-4 cells has been previously shown to manifest the intermediate affinity IL-2 binding. These results may imply that functional expression of IL-2R beta is differentially regulated between humans and mice. Finally, our neutralizing anti IL-2R beta mAb TM-beta 1 will be useful not only for various in vitro studies but also for in vivo studies to directly investigate the possible involvement of the IL-2/IL-2R pathway in the generation and differentiation of T lymphocytes and NK cells. PMID- 1918961 TI - Tumor necrosis factor-alpha dependent cytotoxicity of human skin mast cells is enhanced by anti-IgE antibodies. AB - Mast cells dispersed from human skin and purified by density-gradient centrifugation were cytotoxic toward the mouse fibrosarcoma cell line WEHI-164. Skin mast cells were not cytotoxic toward the NK cell-sensitive cell line K562. Killing of WEHI-164 occurred over a prolonged (greater than 18 h) period of incubation with mast cells and was effectively inhibited by polyclonal antibodies and mAb against TNF-alpha suggesting that this cytokine plays an important role in mast cell-mediated cytotoxicity. Whereas lysates of rat peritoneal mast cells exhibited cytotoxicity toward WEHI-164, this was not found with lysates of unstimulated skin mast cells suggesting that TNF-alpha is not stored preformed in the latter. Killing of WEHI-164 cells by skin mast cells was enhanced by anti-IgE and there was a significant correlation between histamine release and cytotoxicity after activation with this stimulus. We conclude that human skin mast cells are a potential source of TNF-alpha and suggest that these cells, particularly after activation, might contribute to the synthesis of this multifunctional cytokine in inflammatory sites. PMID- 1918960 TI - Induction of macrophage inflammatory protein-1 beta gene expression in human monocytes by lipopolysaccharide and IL-7. AB - HuMIP-1 beta is a member of a gene family of inflammatory cytokines whose expression is induced by proinflammatory and mitogenic stimuli. The gene was rapidly induced in human peripheral blood monocytes by either LPS or IL-7. However, IL-7 was unable to induce HuMIP-1 beta mRNA in peripheral blood T cells. The induction of HuMIP-1 beta mRNA in monocytes by IL-7 or LPS was inhibited by IL-4. The 5'-regulatory region of the HuMIP-1 beta gene was cloned and sequenced. An analysis of this sequence revealed three consensus-binding sites for the nuclear factor PU.1 and three potential glucocorticoid response elements. However, the HuMIP-1 beta gene appears to be unresponsive to dexamethasone. Also present in the 5'-regulatory region was a LPS-responsive element located within 455 bp 5' to the start of transcription. PMID- 1918962 TI - Oscillations in free cytosolic calcium during IgE-mediated stimulation distinguish human basophils from human mast cells. AB - Free cytosolic calcium ([Ca2+]i) levels increase after the stimulation of either human basophils or mast cells with anti-IgE antibody. Previous studies found that the mast cell [Ca2+]i response was graded in magnitude, according to stimulus strength, and that the activated level was free of oscillations. The current studies demonstrate several new features of the mast cell and basophil response. First, in mast cells, the transition to activated [Ca2+]i levels was abrupt (width = 6.5 +/- 2 s), after a period of quiescence whose duration (5 to 300 s) was a function of the strength of the stimulus. At optimal concentrations of anti IgE, 97% of mast cells showed only abrupt transitions and oscillation-free activated calcium levels. In contrast, basophils showed marked oscillations whose magnitudes were partially dependent on the strength of stimulus. Like the mast cell, there was a quiescent period before the first transition and this period was also dependent on the strength of the stimulus. Oscillations were generally superimposed on an elevated [Ca2+]i level at a frequency of 0.5 to 3/min, had half-widths of 5 to 20 s, and were markedly chaotic in the frequency domain. In general, oscillations were more apparent at suboptimal concentrations of anti IgE. Despite the apparent contrast in basophil and mast cell responses, oscillations (1 or 2 in a 10-min period) could be observed in a small percentage of mast cells and some basophils showed characteristics of mast cells. We tentatively conclude that mast cells and basophils utilize a similar mechanism of calcium mobilization but that the nonlinear characteristics of the calcium response may account for the mast cell/basophil differences. These studies indicated that the calcium kinetics, as measured by population averages, did not reflect the kinetics observed at the single cell level. Both mast cells and basophils had characteristics which could be described as graded and characteristics resembling all-or-nothing processes; the magnitude of a response was graded according the strength of stimulus while the kinetics profile appeared as an all-or-nothing event. PMID- 1918963 TI - CD8+ T cells from mice vaccinated against Toxoplasma gondii are cytotoxic for parasite-infected or antigen-pulsed host cells. AB - Mice vaccinated with a live temperature sensitive mutant (TS-4) of Toxoplasma gondii develop complete resistance to subsequent challenge with a highly virulent Toxoplasma strain (RH). Because CD8+ T cells have been demonstrated to be critical to this protective immunity in vivo, the involvement of cytotoxic T lymphocytes in the killing of infected cells in vaccinated mice was investigated. After restimulation in vitro, splenic T cells from vaccinated mice of either the BALB/c or C57BL/6 strains were found to kill syngeneic bone marrow-derived macrophages infected with TS-4 tachyzoites or preincubated with soluble T. gondii Ag. Unimmunized control mice or mice vaccinated with heat-killed TS-4 tachyzoites failed to generate significant CTL activity in vitro. Moreover, the observed lytic reaction was found to be target specific, not killing uninfected or unpulsed macrophages even when included as bystanders in the assay. Target lysis did not depend on the production by the effector cells of either a cytotoxic supernatant factor or IFN-gamma. Depletion of CD8+ cells from the splenic effector cell population, however, abrogated the cytotoxic activity, whereas depletion of CD4+ cells had little effect. The MHC restriction of the Toxoplasma specific cytolytic reaction was confirmed in studies using effector cells from BALB/c mice and targets from congenic or mutant haplotype strains. These experiments indicated that target killing is primarily restricted by genes mapping within the H-2D/Ld loci. Together, these results establish MHC-restricted cytolysis as a major parameter of CD8+ effector function against T. gondii and indicate that, in the case of this protozoan, Ag presentation to CD8+ lymphocytes can occur as a result of either processing within infected cells or exogenous uptake of parasite Ag. PMID- 1918964 TI - Role of bacterial hemolysin production in induction of macrophage Ia expression during infection with Listeria monocytogenes. AB - The production of a hemolytic exotoxin (Hly) termed listeriolysin O (LLO) is a major determinant of the virulence of the Gram-positive bacterium Listeria monocytogenes. As determined by lethal inoculum size, LLO- strains of L. monocytogenes generally are several orders of magnitude less virulent than their LLO+ counterparts. The generation of protective anti-Listeria T cell immunity also has been shown to depend on the LLO phenotype of the bacteria present during primary infection, although the cellular basis of this observation is not known. The experiments described here address the role of LLO in regulation of the expression of class II MHC (Ia) molecules by murine macrophages. Because Ia expression by macrophages and other APC is thought to be a central factor in the generation of T cells specific for bacterial Ag, we have tested the hypothesis that the failure of LLO- strains to elicit anti-Listeria T cell responses might be secondary to an inability of these strains to stimulate increases in macrophage Ia levels. Our results show that the macrophage Ia response after i.p. injection of L. monocytogenes correlates strongly with the LLO phenotype of the bacteria. The presence of LLO+ organisms, even at very small numbers (as few as 10), elicits a striking increase in Ia expression by peritoneal macrophages. In contrast, even at very high numbers (up to 10(6) per mouse), LLO- bacteria fail to stimulate a strong Ia response. We also have analyzed macrophage Ia expression after injection of lysates of Escherichia coli expressing recombinant LLO protein. Similar to the results obtained with LLO+ and LLO- L. monocytogenes, we have observed Ia induction only with LLO+ lysates. Ia induction by this crude recombinant LLO preparation can be inhibited by cholesterol or heat. Furthermore, supernatants derived from cultures of LLO+ (but not LLO-) L. monocytogenes can cause Ia induction when administered via i.p. injection. Taken together, these findings suggest that the failure of macrophages to respond to LLO- organisms with an increase in Ia expression may be a major underlying cause of the failure of these bacteria to induce Listeria-specific protective T cell immunity. Furthermore, we propose that the induction of macrophage Ia expression in response to bacterial toxins such as Hly may represent one component of a set of early, innate immune mechanisms, and that this induction may provide a critical "bridge" to later, acquired, Ag-specific immune processes. PMID- 1918965 TI - Lipopolysaccharide responsiveness is an important factor in the generation of optimal antigen-specific T cell responses during infection with gram-negative bacteria. AB - We previously have found that the endotoxin (LPS) of Gram-negative bacteria is a major determinant of macrophage Ia induction during infection with these organisms. Specifically, i.p. injection of Gram-negative bacteria elicits a striking macrophage Ia response in LPS-responder mice but virtually no response in LPS-low-responder mice. As an extension of these findings, in this report we have tested the hypothesis that the inability of LPS-low responder mice to mount an Ia response during Gram-negative infection may in turn impair their capacity for generation of appropriate antibacterial T cell responses. Our results demonstrate that for a variety Gram-negative organisms (Salmonella typhimurium, Salmonella minnesota, and Escherichia coli), both macrophage Ia induction and the generation of Ag-specific T cell responses are controlled by the lps gene. We also have asked whether the expression of additional toxins (other than LPS) by infecting Gram-negative organisms can "override" this lps gene control of macrophage and T cell responses. We have found that infection of LPS-low responder mice with an E. coli strain that expresses a hemolytic exotoxin (Hly) leads to the induction of macrophage Ia expression as well as the generation of T cell responses to both the Hly molecule and to other E. coli-associated Ag, whereas no responses are generated during infection with a Hly- strain. This result suggests that LPS-low responder mice have no inherent defect in T cell responsiveness to Gram-negative bacterial Ag but rather that these mice fail to receive an LPS-mediated signal required for the induction of Ia expression and subsequent generation of peritoneal T cell immunity. These findings, when taken together with results presented in the accompanying paper, strengthen the argument that bacterial toxin production (and the ability of the host to respond to the toxin) can represent a critical determinant of the induction of macrophage Ia expression and in turn, of Ag-specific T cell responses during bacterial infection. PMID- 1918966 TI - Tumor necrosis factor-alpha triggers antitoxoplasmal activity of IFN-gamma primed macrophages. AB - IFN-gamma is an important mediator of cellular resistance against microbial pathogens and tumor cells due in part to its potent capacity to activate macrophages for enhanced cytotoxicity. The present study demonstrates that TNF alpha regulates the expression of enhanced antimicrobial activity by triggering IFN-gamma primed macrophages to kill or inhibit intracellular Toxoplasma gondii. Resident mouse macrophages stimulated with rIFN-gamma at levels up to 2500 U/ml failed to display enhanced antitoxoplasmal activity when cultured in vitro under low endotoxin conditions (less than 10 pg/ml), but were triggered by addition of small amounts of LPS (0.1 ng/ml). A similar requirement for LPS as a second signal necessary to trigger antitoxoplasmal activity was observed when IFN-gamma was administered to mice in vivo. The essential nature of this triggering step allowed us to explore the role of cytokines that act as endogenous regulators of macrophage activation. rTNF-alpha, although unable to confer antitoxoplasmal activity when used alone to treat macrophages, was capable of triggering IFN gamma-primed macrophages cultured under low endotoxin conditions. The ability of TNF-alpha to trigger IFN-gamma-primed macrophages was blocked by rabbit anti-TNF alpha polyclonal antisera but was not affected by polymyxin B indicating that TNF alpha triggering was not due to contamination with LPS. Collectively, these findings demonstrate that TNF-alpha performs an important regulatory role in the expression of enhanced anti-microbial activity by IFN-gamma-primed macrophages. PMID- 1918968 TI - Natural auto- and polyreactive antibodies differing from antigen-induced antibodies in the H chain CDR3. AB - We describe three sets of natural (preimmune) polyreactive antibodies and Ag induced antibodies that share the same VH-VL combinations. The amino acid homology in the VH and VL segments averaged 92%. These sets were found among 49 neonatal and adult natural mAb that were compared with 35 Ag-induced monoclonals produced during the memory response to phosphocholine (PC)-keyhole limpet hemocyanin. Both groups of monoclonals had been selected on the basis of a restricted fine specificity pattern, namely the ability to recognize PC-protein and p-nitrophenyl phosphocholine but not PC. All of the antibodies were tested for reactivity against a panel of 15 self and foreign Ag. Despite their common fine specificity as the basis for selection, 33/49 natural antibodies were poly/auto reactive whereas 0/35 Ag-induced antibodies had such poly/auto reactive properties. The natural antibodies were encoded by genes representing nine different VH families and several V kappa and V lambda families. There were a few replacement substitutions distinguishing the Ag-induced antibodies from the natural antibodies in each set; however, the most noteworthy difference was the extreme variability of CDR3 in the natural antibodies that differed in both length and amino acid sequence from each other and from Ag-induced antibodies. The results suggest that CDR3 of the H chain may play a critical role in distinguishing poly- from monospecific combining sites in natural and Ag-induced antibodies. PMID- 1918967 TI - Identification and localization of an enhancer for the human lambda L chain Ig gene complex. AB - A strong transcriptional enhancer was identified for the human lambda L chain Ig gene complex. Enhancer activity was measured by activation of the chloramphenicol acetyl transferase (CAT) gene in a transient assay using both mouse and human B lymphoid cell lines. The smallest fragment identified with enhancer activity was 111 bp, which resides 11.7 kb downstream (3') of C lambda 7, a constant region gene we have recently isolated and identified as functional in the human population. Enhancer activity is orientation independent, tissue specific (active in all B cell lines tested and not in a T cell line), and independent of NF kappa B, similar to the mouse lambda enhancers recently reported. The human lambda enhancer is active in both mouse and human B cell lines; interestingly, the mouse lambda enhancers are active in mouse lines but not in a human B cell line. DNA sequence comparison of the mouse and human lambda enhancers indicates a higher degree of homology (average of 72.5%) within the 111-bp enhancer core region identified here than for the remaining flanking sequence compared (average of 42%). This discovery of an enhancer in the human lambda locus (HuE lambda), which is clearly distinct from that of the H and L chain loci, will help to determine the mechanism for the ordered expression and rearrangement of these gene complexes in B cell ontogeny. The presence of only one enhancer in the human C lambda complex 3' of all the C genes suggests that the evolutionary duplication of the L locus differs from that seen in mouse; in mouse the duplication unit was JCJC-enhancer, whereas the human JC lambda s duplicated without the enhancer. PMID- 1918969 TI - Role of lipopolysaccharide and IL-4 in control of transcription of the class II A alpha gene. AB - The class II (Ia) MHC molecules are cell surface proteins that regulate the activation of T cells. B lymphocyte expression of class II molecules has been shown to be influenced by a number of external stimuli. It has been previously demonstrated that treatment of these cells with IL-4 leads to an increase in class II gene transcription at 18 h as well as to an increase in steady state class II mRNA. It has also been previously demonstrated that LPS treatment of splenic B cells from athymic mice results in a decrease in steady state mRNA encoding the A alpha class II protein. This decrease persists for at least 18 h. Nuclear run-on transcription assays now demonstrate that although steady state mRNA levels for A alpha are decreased by LPS treatment of athymic mouse lymphocytes, LPS does not decrease A alpha gene transcription, but rather modestly activates transcription of this class II gene. LPS and IL-4 have been demonstrated to be synergistic stimuli for a number of genes. Costimulation of splenic lymphocytes from athymic mice with IL-4 plus LPS leads to activation of transcription, but the increase in transcription is no more than that seen with IL-4 stimulation alone. However, in costimulated lymphocytes, steady state A alpha-encoding mRNA levels are intermediate between the increased levels seen with IL-4 stimulation and the decreased levels seen with LPS stimulation. Therefore, LPS and IL-4 act nonsynergistically in class II gene transcription and the effects of LPS in decreasing steady state mRNA are most likely posttranscriptional. An IL-4-inducible and an LPS-inducible DNA-binding protein have been previously identified in splenic lymphocytes from athymic mice. Both nuclear binding proteins form complexes with the same DNA fragments from a control region of the A alpha gene. These nucleoprotein complexes comigrate under nondenaturing conditions and display identical patterns of binding with a panel of oligonucleotide competitors. Oligonucleotides representing protein binding sites of the IL-4 and LPS-induced DNA-binding proteins cross-compete for protein binding. Therefore, the binding proteins induced by LPS and IL-4 are likely related, and may function at different efficiencies as activators of A alpha gene transcription. PMID- 1918970 TI - c-fos transcriptional activation by IL-2 in mouse CTL-L2 cells is mediated through two distinct signal transduction pathways converging on the same enhancer element. AB - The c-fos protooncogene is suspected to play a major role during the activation of cells from different lineages. In particular, c-fos transcription is induced upon entry into a proliferation cycle in a wide variety of cell types. In this study, we have transfected an IL-2-dependent murine T cell line with chloramphenicol acetyl transferase (CAT) reporter constructs, harboring various regions of the human c-fos promoter. We show that IL-2 induces activation of fos CAT reporter constructs in these cells. Furthermore, the induction by IL-2 is mediated through a dyad symmetry element, the serum response element, which is also responsible for fos CAT reporter constructs activation by PMA, a pharmacologic activator of the protein kinase C (PKC). To assess any involvement of PKC in signal transduction for fos CAT reporter activation by IL-2, CTL-L2 cells were PKC-depleted by treatment with high doses of PMA. Such a treatment abolished the transcriptional response of fos CAT reporter constructs to PMA. In contrast, IL-2 was still able to activate fos CAT transcription, albeit with a lower efficiency. These results suggest that PMA-sensitive PKC might be part of intracellular transduction pathways leading to c-fos transcriptional activation by IL-2, and that at least one alternate pathway participates in the complete response. However, these distinct signal transduction pathways have the same DNA target on c-fos promoter, the serum response element. PMID- 1918971 TI - Anti-IgM-mediated growth inhibition of a human B lymphoma cell line is independent of phosphatidylinositol turnover and protein kinase C activation and involves tyrosine phosphorylation. AB - The RL cell line is an EBV-negative, surface IgM, IgD-positive B lymphoma line, which is significantly growth arrested in the presence of acrylamide-linked antibodies to the surface IgM receptor. We demonstrate here that activation of protein kinase C (PKC) with PMA abrogates anti-IgM-induced phosphoinositide turnover and Ca2+ mobilization; however, growth inhibition is not affected. In addition, inhibitors of PKC are unable to reverse the anti-IgM-mediated growth inhibition. Two-dimensional gel electrophoresis reveals a different pattern of protein phosphorylation after treatment of RL with PMA or anti-IgM. These data strongly suggest that anti-IgM-induced growth inhibition does not rely on phospholipase C-mediated phosphoinositide turnover, Ca2+ mobilization, or PKC activation. On the other hand, the phosphatase inhibitor orthovanadate results in an augmentation of proteins phosphorylated on tyrosine and the growth inhibition which follows anti-IgM treatment. Furthermore, protein tyrosine kinase inhibitors, genistein and herbimycin A, are able to reverse the anti-IgM-induced inhibition of growth. These data demonstrate that multiple signaling pathways are activated by the interaction of anti-IgM with its ligand, and suggest that tyrosine kinase activation is a critical component of the inhibitory response. PMID- 1918972 TI - Abrogation of tumorigenicity by MHC class II antigen expression requires the cytoplasmic domain of the class II molecule. AB - Transfection of syngeneic MHC class II genes into the lethal mouse SaI tumor abrogates the malignancy of the tumor in the autologous host, and protects the host against subsequent challenges with the wild type class II- tumor. We have hypothesized that the transfectants induce protective immunity by functioning as APC for tumor peptides, and stimulating tumor-specific Th cells. Recent in vitro studies suggest that Ag presentation by class II-restricted APC requires the cytoplasmic domain of the class II molecule, and may involve intracellular signaling via the cytoplasmic domain. To determine if the class II cytoplasmic domain is required for enhanced tumor-specific immunity, SaI mouse sarcoma cells were transfected with syngeneic Aak and Abk genes with truncated cytoplasmic domains. These transfectants are as malignant as wild type class II- SaI cells in autologous A/J mice. Stimulation of tumor-specific immunity by class II+ tumor cells is therefore dependent on the class II cytoplasmic region, and may involve intracellular signaling events. PMID- 1918973 TI - Idiotypes: concepts and applications. PMID- 1918974 TI - Similarity and difference in the mechanisms of neonatally induced tolerance and cyclophosphamide-induced tolerance in mice. AB - The mechanisms of cyclophosphamide (CP)-induced tolerance were investigated by comparing with those of neonatally induced tolerance. When C3H/He Slc (C3H; H-2k, Mls-1b) mice were given i.v. either AKR/J Sea (AKR; H-2k, Mls-1a) or (AKR x C3H)F1 (AKC3F1; H-2k, Mls-1a/b) spleen cells and treated i.p. with CP 2 days later, a long-lasting skin allograft tolerance to AKR was induced in each case without any signs of graft-vs-host disease (GVHD). However, typical signs of GVHD were observed in the C3H mice neonatally tolerized with AKR spleen cells, but not in those tolerized with AKC3F1 spleen cells. The expression of TCR V beta 6, which is strongly correlated with the reactivity to Mls-1a Ag (of donor AKR origin), in the periphery was quite different between the two types of tolerant C3H mice. Namely, in the lymph nodes of the C3H mice tolerized with AKR spleen cells and CP, only CD4(+)-V beta 6+, but not CD8(+)-V beta 6+, T cells selectively disappeared, whereas both of them were abrogated in the lymph nodes of the C3H mice neonatally tolerized of AKR. By contrast, in the thymus of the two types of tolerant C3H mice, both CD4+CD8- and CD4-CD8+ single-positive thymocytes expressing TCR V beta 6 were clonally deleted, suggesting that the thymic involvement was the same in each type of tolerance. These results suggest that the preferential disappearance of the CD4(+)-V beta 6+ T cells (of host origin) and the effector T cells of GVHD (of donor origin) occurred only in the periphery of the C3H mice tolerized with AKR spleen cells plus CP and was attributable to the destruction of Ag-stimulated T cells by the CP treatment. In contrast, the intrathymic clonal deletion of immature V beta 6+ T cells was a common mechanism for both of the tolerance induction systems. PMID- 1918975 TI - Murine granulated metrial gland cells at uterine implantation sites are natural killer lineage cells. AB - Granulated metrial gland (GMG) cells, a population of morphologically distinct, bone marrow-derived cells in murine decidua that react with mAb 4H12, are shown in this report to express NK-specific Ag and to become cytolytic to the NK cell target YAC-1 when cultured in the lymphokine IL-2. When 1-mm3 explants of 8-day decidual tissue were cultured with IL-2, large numbers of 4H12+ GMG cells migrated out of the tissue. Migration was dependent on the amount of IL-2 used. This explant technique was used to isolate a pure population of GMG cells. The migratory activated GMG cells were phenotypically 4H12+, NK1.1+, LGL-1+/-, CD3-, and MAC-1-. Furthermore, the IL-2-activated GMG cells killed YAC-1 but not P815 cells in a 4-h 51Cr-release cytotoxicity assay. 4H12+ GMG cells from collagenase digested decidual tissue also were analyzed for the presence of NK lineage Ag by flow cytometry and shown to coexpress the NK-associated Ag NK1.1 and ASGM1 but not the T cell Ag CD3 or macrophage Ag MAC-1 or F4/80. GMG cells isolated by collagenase digestion did not express LGL-1, an Ag associated with lytic NK cells. Our results demonstrate that GMG cells express Ag and functions characteristic of NK cells, and thus GMG cells can be assigned to the NK lineage. The possible relevance of NK cells at implantation sites is discussed. PMID- 1918976 TI - B lymphocytes from the autoimmune-prone mouse strain MLR/lpr manifest an intrinsic defect in tetraparental MRL/lpr in equilibrium DBA/2 chimeras. AB - Data are presented showing that MRL/lpr in equilibrium DBA/2 tetraparental (allophenic) chimeras, unlike conventional lpr/lpr----+/lpr bone marrow chimeras, fail to develop graft-vs-host disease; instead they develop full-blown lymphoproliferation and autoantibody formation typical of unmanipulated MRL/lpr mice. The increase in the splenic and especially the lymph node mass is comprised predominantly of MRL/lpr-derived cells and all of the serum IgG2a is MRL/lpr derived. This dominance of MRL/lpr lymphoid activity occurred even in chimeras where greater than 90% of the skin and/or bone marrow cells were of the DBA/2 type. These results demonstrate the failure of the lpr environment to recruit normal B and T cells into the autoimmune process, the inability of normal cells to suppress MRL/lpr disease, and indicate further that the lpr mutation has an intrinsic effect on lymphocytes of both the B and T lineages. PMID- 1918978 TI - IFN-gamma enhances sensitivity of human macrophages to extracellular ATP-mediated lysis. AB - In an effort to determine the mechanism by which autologous monocytes are killed by lymphokine-activated killer cells, soluble mediators were examined for their direct effect on target cells. Extracellular ATP (ATPo), but not ADP, was found to lyse human culture-derived macrophages in a 6-h 51Cr-release assay. Treatment of monocytes with human rIFN-gamma rendered those cells significantly more sensitive to ATPo compared to untreated or granulocyte-macrophage CSF-(GM-CSF) treated cells. In addition, IFN-gamma-treated macrophages released approximately 80% of 51Cr label within 15 min after the addition of ATPo, whereas GM-CSF treated cells did not release significant levels of radiolabel until 4 to 6 h after initial stimulation with ATPo. Time course studies also demonstrated that 3 days of incubation of macrophages with IFN-gamma induced optimal sensitivity to ATPo, although some effect was noted after 4 h of incubation. Thus, IFN-gamma treatment of macrophages elicited increased sensitivity to ATPo-mediated lysis, a phenomenon characterized by rapid release of 51Cr from labeled cells and which is possibly due to induction or activation of surface ATP-binding receptors different from those present on GM-CSF-treated or untreated macrophages. PMID- 1918977 TI - Thymic microenvironment induces HIV expression. Physiologic secretion of IL-6 by thymic epithelial cells up-regulates virus expression in chronically infected cells. AB - The hallmark of infection with HIV-1 is progressive depletion and qualitative dysfunction of the CD4+ Th cell population in infected individuals. Clinical trials of antiretroviral agents have shown that, despite suppression of virus replication, regeneration of the T cell pool does not occur. One proposed explanation for the defective regenerative capacity of the CD4+ T cell pool is infection of early T lymphocyte progenitors or stem cells. An additional explanation could be failure of cells of the intrathymic microenvironment (thymic epithelial (TE) cells) to carry out critical nurturing functions for developing thymocytes, i.e., secretion of thymocyte-trophic cytokines and expression of adhesion molecules. This study examines the effect of HIV on cultured TE cells and determines the role of TE cells in the regulation of viral expression in chronically HIV-infected cells. We found no evidence of infection of TE cells after exposure to HIV-1. However, normal human serum induced secretion of IL-6 by TE cells; induction of TE IL-6 was partially blocked by anti-IFN-gamma antibodies. Moreover, supernatants from TE cells maintained in normal human serum up-regulated HIV replication in chronically HIV-1-infected cells. Because intrathymic T cell precursors can be infected with HIV and T cell precursors come into close contact with TE cells in the thymus, IL-6 secreted by TE cells during normal intrathymic development may induce HIV expression in infected thymocytes in vivo and promote the intrathymic spread of HIV. PMID- 1918979 TI - Macrophage inflammatory protein (MIP)-1 beta abrogates the capacity of MIP-1 alpha to suppress myeloid progenitor cell growth. AB - The effects of recombinant murine macrophage inflammatory protein (MIP)-1 beta and MIP-2 on the suppressive activity of MIP-1 alpha were tested using colony formation by human and murine bone marrow burst-forming unit-erythroid (BFU-E), colony-forming unit-granulocyte erythroid macrophage, megakaryocyte (CFU-GEMM), and colony-forming unit-granulocyte macrophage (CFU-GM) progenitor cells. MIP-1 beta, but not MIP-2, when added with MIP-1 alpha to cells, blocked the suppressive effects of MIP-1 alpha on both human and murine BFU-E, CFU-GEMM, and CFU-GM colony formation. Similar results were observed regardless of the early acting cytokines used: human rGM-CSF plus human rIL-3, and two recently described potent cytokines, a genetically engineered human rGM-CSF/IL-3 fusion protein and MGF, a c-kit ligand. The more potent the stimuli, the greater the suppressive activity noted. Pulse treatment of hu bone marrow cells with MIP-1 alpha at 4 degrees C for 1 h was as effective in inhibiting colony formation as continuous exposure of cells to MIP-1 alpha, and the pulsing effect with MIP-1 alpha could not be overcome by subsequent exposure of cells to MIP-1 beta. Also, pulse exposure of cells to MIP-1 beta blocked the activity of subsequently added MIP-1 alpha. For specificity, the action of a nonrelated myelosuppressive factor H ferritin, was compared. MIP-1 alpha and H-ferritin were shown to act on similar target populations of early BFU-E, CFU-GEMM, and CFU-GM. MIP-1 beta did not block the suppressive activity of H-ferritin. Also, hemin and an inactive recombinant human H-ferritin mutein counteracted the suppressive effects of the wildtype H ferritin molecule, but did not block the suppressive effects of MIP-1 alpha. These results show that MIP-1 beta's ability to block the action of MIP-1 alpha is specific. In addition, the results suggest that MIP-1 alpha and MIP-beta can, through rapid action, modulate early myeloid progenitor cell proliferation. PMID- 1918980 TI - Cytokine-induced IL-1 beta gene expression in the human polymorphonuclear leukocyte: transcriptional and post-transcriptional regulation by tumor necrosis factor and IL-1. AB - We have previously demonstrated that Il-1 and TNF could rapidly, but transiently, induce gene expression of Il-1 beta in human polymorphonuclear leukocytes (PMN) at both the protein and mRNA level. Additionally, we demonstrated a cooperative effect of Il-1 and TNF on the kinetics of induction of Il-1 beta mRNA and protein. In order to better understand the molecular basis of Il-1 beta induction, we have further investigated the regulation of Il-1 and TNF-induced gene expression in the PMN. Using nuclear run-on transcription analysis, we found that within 1 h Il-1, TNF, and TNF plus Il-1 induced the transcription of the Il 1 beta gene by 33-, 61-, and 99-fold, respectively. By 2 h, the levels of transcription had been reduced to approximately 50% of peak levels for TNF- and TNF plus Il-1-treated PMN, and to near noninduced levels in Il-1-treated PMN. We also found that these cytokines induced stable mRNA, i.e., Il-1 beta mRNA t1/2 for Il-1-, TNF-, and TNF plus Il-1-induced PMN were 57, 94, and 86 min, respectively. By 2 h, when steady state levels of Il-1 beta mRNA were found to decrease, Il-1 beta mRNA t1/2 had fallen to approximately 18 min for all cytokine treatments. To determine if protein synthesis was required for induction of Il-1 beta gene expression, we treated PMN simultaneously with cytokines and cycloheximide, and found that cycloheximide enhanced the accumulation of Il-1 induced Il-1 beta mRNA, but abrogated the accumulation of Il-1 beta mRNA, by TNF- or TNF plus Il-1-treated PMN. This abrogation of Il-1 beta mRNA accumulation was not caused by inhibition of induction of Il-1 beta transcription because TNF induction of transcription of Il-1 beta was not affected by simultaneous treatment with cycloheximide. Thus, we report that Il-1 and TNF regulate IL-1 beta gene expression via both transcriptional and post-transcriptional mechanisms in vitro. PMID- 1918981 TI - Synergistic effect of tumor necrosis factor-alpha- and diphtheria toxin-mediated cytotoxicity in sensitive and resistant human ovarian tumor cell lines. AB - Recent studies have demonstrated that diphtheria toxin (DTX) also mediates target cell lysis, and the mechanism of cytotoxicity has many features similar to those of cytotoxicity mediated by TNF-alpha. Thus, we hypothesized that DTX and TNF alpha, used in combination, may result in either additive or synergistic cytotoxic activity. This was examined on three human ovarian carcinoma cell lines chosen for their differing sensitivities to TNF-alpha and DTX, i.e., 222, which is sensitive to both TNF-alpha and DTX, 222TR, a TNF-alpha-resistant DTX sensitive variant of 222, and SKOV-3, which is resistant to both DTX and TNF alpha. The simultaneous use of DTX and TNF-alpha at suboptimal concentrations resulted in synergistic cytotoxic activity against all three lines tested, thus overcoming the TNF-alpha resistance of 222TR and the double resistance of SKOV-3. DNA fragmentation was observed in all three lines treated with DTX and TNF-alpha and occurred as early as 4 h after treatment. Cycloheximide, actinomycin D, or emetine, at concentrations causing greater than 90% protein synthesis inhibition, did not result in cytotoxicity alone or synergy with TNF-alpha, suggesting that synergy by DTX was not due to its ability to inhibit protein synthesis. The use of energy poisons and pH conditions that inhibit DTX-mediated cytotoxicity resulted in the abrogation of synergy. These findings show that the two cytotoxic agents TNF-alpha and DTX, when used at suboptimal concentrations, synergize in their cytotoxic activity against sensitive and resistant cell lines. Because the SKOV-3 cell line used here is also resistant to chemotherapeutic drugs, combination treatment with DTX and TNF-alpha may be beneficial in overcoming drug resistance. PMID- 1918982 TI - IL-3-induced generation of alkylacylglycerol and diacylglycerol in an IL-3 dependent cell line. AB - The hematopoietic growth factor IL-3 promotes the proliferation and development of several hematopoietic lineages. Inasmuch as protein kinase C has been suggested to mediate the response of IL-3, we examined the accumulation of diradylglycerols (DG) in response to IL-3 in CFTL-12 cells, a murine mast cell line that requires IL-3 for growth. Exposure of CFTL-12 cells to IL-3 resulted in the conversion of [3H]myristate-labeled lipids to DG. Mass analysis of the DG of CFTL-12 cells cultured in the presence of IL-3 showed that 58% was the ether linked form, alkylacylglycerol, and 42% was diacylglycerol. The levels of both alkylacylglycerol and diacylglycerol declined when CFTL-12 cells were withdrawn from IL-3 and became quiescent. Stimulation of quiescent cells with IL-3 produced an acute increase in the mass of both alkylacylglycerol and diacylglycerol, consistent with phosphatidylcholine as a significant source. The effects of PMA on the generation of DG were examined to explore the role of protein kinase C activation in the response to IL-3. PMA stimulated an increase in DG accumulation that was not augmented by the simultaneous addition of IL-3. Down-modulation of protein kinase C by long term PMA treatment reduced, but did not eliminate, the IL-3-stimulated increase in DG, suggesting that protein kinase C activation results in an amplification of the initial accumulation of DG. These results indicate a role for DG, generated through the hydrolysis of phosphatidylcholine, in the induction of protein kinase C activity and the events leading to cell proliferation in response to IL-3. PMID- 1918983 TI - IL-6 and IL-6 receptor modulation by IFN-gamma and tumor necrosis factor-alpha in human monocytic cell line (THP-1). Priming effect of IFN-gamma. AB - The present work is a detailed study of the mechanism of IFN-gamma- and TNF-alpha triggered IL-6 secretion and IL-6 gene expression in human monocytic THP-1 cells and of the effect of these cytokines on the expression of IL-6 surface receptor and IL-6R gene. Although TNF-alpha was shown to stimulate IL-6 expression in fibroblasts in monocytic THP-1 cells, IFN-gamma is required for TNF to induce IL 6 expression. The results reported here demonstrate that combined treatment of THP-1 cells with IFN-gamma + TNF-alpha induced IL-6 mRNA expression, whereas no significant induction was obtained by either cytokine alone. Nuclear run-on transcription assay showed that the increased level of IL-6 mRNA induced by IFN gamma + TNF-alpha was associated with induction of gene transcription. Sequential stimulation of THP-1 cells by IFN-gamma and subsequently by TNF-alpha did not allow IL-6 gene induction, suggesting that IFN-gamma and TNF-alpha induced or activated different signaling factors which should act together to trigger IL-6 gene transcription. IFN-gamma pretreatment followed by IFN-gamma + TNF-alpha restimulation led to superinduction of the IL-6 gene expression with a concomitant increase in IL-6-secreted activity. This priming effect of IFN-gamma is dependent on active protein synthesis. Biochemical characterization of IL-6 proteins secreted by THP-1 cells by Western blotting and affinity chromatography allowed identification of a major IL-6 molecular species of 42 kDa and a minor one of 23 kDa. Furthermore, we showed here that IFN-gamma increased the IL-6R mRNA level with a concomitant increase in IL-6-specific binding to surface receptors. On the contrary, treatment with IFN-gamma + TNF-alpha reduced the level of IL-6R mRNA and IL-6 binding to THP-1 cells probably due to a ligand mediated effect. Taken together, results reported here provide evidence that functional interaction between IFN-gamma and TNF-alpha is involved in the regulation of IL-6 and IL-6R expression in monocytic cells. Control of IL-6 production and IL-6R expression may be one of the important homeostatic properties of IFN-gamma. PMID- 1918984 TI - Membrane vesiculation protects erythrocytes from destruction by complement. AB - Nucleated cells can resist attack by C by exocytosis or endocytosis of the terminal C components C5b-9 (membrane attack complex) (MAC), but it is generally accepted that formation of a single MAC channel on E leads to lysis (one-hit theory). We find that human and guinea pig E, but not SRBC, can eliminate the MAC from the membrane in the form of microvesicles and escape destruction. When guinea pig or human E are incubated with C5b-9, vesiculation proceeds without a lag and is detected at nonlytic doses of C9. Continuous Ca2+ influx is required for vesiculation. The amount of released vesicles is in direct relation to Ca2+ concentration, and the increase in vesiculation is associated with a parallel decrease in lysis. SRBC, which do not vesiculate when Ca2+ loaded, are lysed by C5b-9 with the same efficiency in the presence or absence of Ca2+. Vesicles released from guinea pig RBC under C5b-9 attack are enriched in C9 by a factor of 10, compared with the unlysed cells, and by a factor of 3 to 4, compared with ghosts. We conclude that E are protected from lysis not only by CD59 and C8bp/HRF, which prevent MAC assembly, but also by selective elimination of the MAC. PMID- 1918985 TI - Rapid intracellular pathway gives rise to cell surface expression of the MHC class II-associated invariant chain (CD74). AB - In previous investigations, it had been shown that class II and associated invariant polypeptides are sorted to an endocytic route where transport is delayed. Invariant chain (Ii) is degraded in a post-Golgi compartment, presumably an endosomal vesicle, and only class II molecules emerge on the cell surface. By using a mAb against the extracytoplasmic domain of human Ii, we demonstrate, by electron microscopy and by cytofluorometry, surface expression of Ii on lymphoma cells and on human B lymphocytes. We examined surface expression of Ii upon inhibition by brefeldin A of intracellular transport from the endoplasmic reticulum to the Golgi stack. This treatment rapidly depletes the cell surface of Ii. In the subsequent absence of brefeldin A, Ii appears rapidly at the cell surface. Within 5 h, the previous level of surface Ii (sIi) is reconstituted. Chloroquine abrogates depletion of sIi by brefeldin A, apparently by inhibition of internalization of sIi. Because on its route to the cell surface Ii is not proteolytically digested, it was possible that Ii and associated class II molecules are not separated on this pathway. Immunochemical studies reveal that on the cell surface of a B lymphoma cell line a proportion of Ii and class II polypeptides are associated. PMID- 1918986 TI - A role for transforming growth factor-beta 1 in regulating natural killer cell and T lymphocyte proliferative responses during acute infection with lymphocytic choriomeningitis virus. AB - The role of transforming growth factor beta 1 (TGF-beta 1) in regulating NK and T cell proliferation during acute viral infections was investigated. After infection of mice with lymphocytic choriomeningitis virus, NK cell proliferation peaks on day 3 and subsides by days 5 to 7 postinfection, whereas T cell proliferation peaks on day 7 and declines by days 9 to 14 postinfection. As TGF beta 1 has been shown to inhibit lymphocyte proliferation in culture, the production and function of TGF-beta 1 during infection was evaluated in this model. Northern blot analysis demonstrated that the accumulation of TGF-beta 1 transcripts remained relatively constant in total splenic leukocytes during infection. The Mv 1 Lu mink lung cell bioassay was modified and used to evaluate the production of biologically active TGF-beta 1 during infection. Media conditioned with splenic leukocytes isolated from infected mice contained factors that inhibited DNA synthesis by the Mv 1 Lu cells. Low levels of inhibition were observed with conditioned media prepared on day 3 postinfection and high levels of inhibition were observed with conditioned media prepared on days 5 through 14 postinfection. Neutralization with antibodies specific for TGF-beta 1 demonstrated that TGF-beta 1 contributed to the inhibitory activity. As TGF-beta 1 was produced at times coinciding with the decline in NK cell proliferation, the TGF-beta 1 sensitivity of in vivo-elicited NK cells was evaluated. In vitro and in vivo studies demonstrated that NK cell proliferation was extremely sensitive to inhibition by TGF-beta 1. In culture, TGF-beta 1 had an ID50 of 8 pg/ml for inhibiting DNA synthesis by blast NK cells. In vivo, administration of a total of 0.18 micrograms of TGF-beta 1 resulted in a 93% inhibition of NK cell-mediated lytic units per spleen on day 3 postinfection. The inhibition was a result of a block in NK cell proliferation, as administration of TGF-beta 1 profoundly suppressed the appearance of blast size NK cells and the incorporation of [3H] thymidine by NK cell-enriched, blast lymphocyte populations on day 3 postinfection. In contrast to NK cell proliferation, T cell proliferation was not inhibited by up to 100-fold higher concentrations of the factor in vitro or in vivo. Taken together, these data demonstrate that TGF-beta 1 is an important regulator of NK cell proliferation in vivo. Furthermore, the results indicate that differential sensitivity to TGF-beta 1 may contribute to the coordination of NK and T cell responses during viral infections. PMID- 1918987 TI - Tumor necrosis factor-independent protective effect of recombinant IFN-gamma against acute toxoplasmosis in T cell-deficient mice. AB - rIFN-gamma conferred remarkable resistance against acute infection with Toxoplasma gondii in T cell-deficient (athymic nude) mice. Mice that received an i.p. injection of rIFN-gamma every other day beginning 24 h before infection for a total of eight doses survived significantly longer than untreated control mice although all of the treated mice died after the lymphokine was discontinued. Mice that received 14 doses of rIFN-gamma survived significantly longer than those that received eight doses of the lymphokine although mice started dying soon after the final (14th) injection of rIFN-gamma and eventually all of the treated mice died. Histologic study revealed that the IFN-gamma treatment prevented proliferation of the organisms in all organs examined, including brain, lung, heart, liver, and spleen. The treatment was effective even when started 1 day after infection. Peritoneal macrophages obtained from mice injected with rIFN gamma were activated and effectively killed tachyzoites of T. gondii in vitro. TNF activity could not be detected in sera of the infected mice during treatment with rIFN-gamma. Administration of anti-TNF antibody did not affect the protective effect of rIFN-gamma against T. gondii infection. These facts indicate that rIFN-gamma can confer resistance to acute infection with T. gondii without collaboration of lymphokines derived from T cells and TNF. This suggests that rIFN-gamma may be effective for therapy of toxoplasmosis in immunosuppressed patients who have impaired activity of T cell function, especially those with AIDS. PMID- 1918988 TI - Distinct patterns of expression of MHC class I and beta 2-microglobulin transcripts at early stages of mouse development. AB - The class I surface Ag recognized during tissue graft rejection are composed of a 40- to 45-kDa H chain and a 12-kDa L chain, beta 2-microglobulin (beta 2m). Regulation of MHC gene expression during early development is thought to play an essential role in maternal tolerance of the fetal allograft. Here we used in situ hybridization techniques to characterize the temporal and spatial pattern of expression of MHC class I mRNA in the developing mouse embryo. MHC class I transcripts were initially detected at day 9.5 postcoitus in the primary and secondary trophoblast giant cell populations. At this stage, none of the remaining fetal components of the developing placenta expresses MHC class I mRNA. By contrast, the outer zone of trophoblast giant cells is the only trophectoderm derived tissue in the developing placenta that does not express detectable levels of beta 2m mRNA. These findings indicate that the onset of MHC class I and beta 2m gene expression in early postimplantation stage embryos is not coordinately regulated. In addition, we made use of pluripotent embryonic stem (ES) cells to study developmental regulation of MHC class I and beta 2m gene expression in vitro. ES cells can be induced to form endoderm-like cells by the technique of suspension culture. In contrast to retinoic acid-treated F9 cells, the endoderm derived from ES cells expressed high levels of beta 2m mRNA, but no detectable MHC class I transcripts. These findings are consistent with results of our in situ hybridization experiments showing high levels of expression of beta 2m mRNA, and extremely weak expression of MHC class I transcripts in derivatives of the visceral endoderm in vivo. PMID- 1918989 TI - Repertoire diversity of antibody response to bacterial antigens in aged mice. II. Phosphorylcholine-antibody in young and aged mice differ in both VH/VL gene repertoire and in specificity. AB - Aging of mice is accompanied by both quantitative and qualitative changes in antibody responses to phosphorylcholine (PC), an immunodominant epitope of Streptococcus pneumoniae R36a strain (Pn). In order to study these changes at the molecular level, we generated PC-specific hybridomas from young (3 to 4 mo) and aged (20 to 24 mo) mice of different strains after primary immunization with S. pneumoniae R36a strain. These mAb were tested for Ig VH and VL gene family utilization, idiotopic repertoire, and cross-reactivity with unrelated Ag. Hybridomas from young mice (BALB/c, C57BL/6, and D1.LP) uniformly expressed the VH-S107 and V kappa-22 genes as well as most idiotopes of the T15 family, which were identified with different anti-T15 mAb. In contrast, the PC-reactive mAb from aged mice were quite heterogeneous: only 2 out of 13 utilized VHS107, 1 of 13 used VH7183, and 3 of 13 used VHJ558 gene family. Moreover, none of these mAb used L chain encoded by V kappa 22(0/13), but surprisingly they frequently expressed some of the T15 idiotope. In addition, the PC-binding mAb from aged mice showed broad cross-reactivity with various mouse and foreign proteins, whereas the mAb from young mice did not. These results demonstrate the genetic shift in antibody response of aging mice to PC, which is accompanied by a change in the antibody specificity. Interestingly, the qualitative repertoire change appears to be unrelated to the magnitude of antibody response, for the aged BALB/c mice maintain a very high reactivity to PC. PMID- 1918991 TI - Molecular mapping of murine I region recombinants. III. Crossing over at two discrete sites within the beta 1-beta 2 intron of the E beta gene. AB - The murine MHC provides a unique genetic system for studying meiotic recombination. A large number of murine H-2 recombinants cross over within a stretch of the E beta gene referred to as the E beta hot spot. The crossing over of eight such recombinants, derived from the s and k haplotypes, was studied at the nucleotide level. A 3-kb stretch of DNA, 3' to the beta 1 exon of the E beta gene, was sequenced after amplification of the genomic DNA from B10.S (one of the parental strains) by polymerase chain reaction. A number of sequence variations were identified with respect to B10.A (the other parental strain). Examination of these sequence variations by RFLP, simple sequence length polymorphism, as well as direct sequencing after polymerase chain reaction-amplification of genomic DNA from the recombinants led to unambiguous identification of the cross-over sites. Although all eight recombinants crossed over within the beta 1-beta 2 intron, two discrete nonoverlapping sites were involved. Five of the recombinants B10.BASR1, B10.ASR1, B10.ASR12, B10.HTT, and B10.S(9R) crossed over within a maximum of 395 bp of DNA 3' to the beta 1 exon. The remaining three recombinants B10.ASR7, B10.ASR11, and B10.S(8R) crossed over within 950 bp of DNA, adjacent to the cross over site noted above. Each of these stretches of DNA was completely identical in the two parental haplotypes precluding further dissection of the cross-over sites. These cross-over sites are within those reported for the b and k recombination. PMID- 1918990 TI - The murine Slp gene. Additional evidence that sex-limited protein has no biologic function. AB - Sex-limited protein (Slp) is a mouse serum protein of unknown function that has approximately 95% amino acid sequence identity with murine complement component C4 but is inactive in the complement pathway. The gene for Slp lies in the S region of the murine H-2 complex adjacent to the gene Cyp21 that encodes the Cytochrome P-450 enzyme steroid 21-hydroxylase. We report the sequence of a 26,307 bp long segment of the mouse genome that includes both the Slp and Cyp21 genes. The sequence reported was assembled from the sequences of three overlapping lambda phage genomic clones from mouse strain B10.WR, which carries four tandem pairs of Slp and Cyp21 genes. We also report the sequence of a fourth lambda clone, 12,539 bp in length, carrying parts of a distinct pair of Slp and Cyp21 genes from B10.WR mice. The Slp gene at 14.3 kb in length is about 1 kb shorter than the C4 gene; this difference is due primarily to absences of a simple repetitive sequence and a middle repetitive MT element in the corresponding introns 14 and 15, respectively. The gene sequence reveals an intron/exon organization identical to that of the murine C4 gene, and also that the 9 nucleotide deletion in exon 18, which appears to be directly responsible for the absence of complement activity, is unrelated to differences in intron sequences. Detailed comparisons of C4 and Slp gene sequences indicate that nucleotide substitutions in the Slp gene are occurring at approximately the same rate in both exons and introns. This implies that the murine Slp gene resembles a pseudogene and supports previously reported evidence that the Slp protein has no biologic function. PMID- 1918992 TI - The rheumatoid factor reactivity of a human IgG monoclonal autoantibody is encoded by a variant V kappa II L chain gene. AB - To determine the genetic and molecular basis for rheumatoid factor (RF) autoantibody reactivity in patients with destructive, erosive arthritis, we established a human lymphoblastoid cell line (hRF-1) from a patient with polyarthritis that produced an IgG RF mAb, mAb hRF-1. Studies of isolated H and L chains showed that the specificity of RF reactivity is conferred by mAb hRF-1 L chains. The L chain gene was cloned from a cDNA library prepared from hRF-1 cells. The nucleotide sequence was similar to known V kappa II L chains except for a two nucleotide change corresponding to a change of two amino acids in an invariable region of FR3. A germ-line gene with one of the nucleotide changes was identified by polymerase chain reaction in multiple cell lines, including K562 that does not rearrange Ig genes, but the other nucleotide change appeared to be due to mutation. Either or both of these amino acid changes may contribute to the RF reactivity, because an antibody with the same V kappa II L chain except for these two amino acid changes in FR3 did not have RF reactivity. The RF reactivity of isolated L chains from mAb hRF-1 was confirmed by transfecting COS cells with an expression vector encoding the hRF-1 kappa-chain and showing that the secreted k-chains had RF reactivity. Expression of this variant V kappa II L chain gene may form the basis for RF autoantibody reactivity in some patients. PMID- 1918993 TI - Cellular models of macrophage tumoricidal effector mechanisms in vitro. Characterization of cytolytic responses to tumor necrosis factor and nitric oxide pathways in vitro. AB - The recently described L-arginine-dependent nitric oxide (NO) pathway has been proposed to interact synergistically with the TNF pathway in murine macrophage mediated tumor cytotoxicity in vitro. We have employed an experimental construct in which these two pathways were independently expressed by two different effector cell populations. The TNF-dependent pathway was committed by murine 3T3 cells transfected with the cDNA encoding human pro-TNF. The NO pathway was executed by the murine EMT-6 mammary adenocarcinoma cell line treated with murine rIFN-gamma and LPS. Controls for the TNF pathway committed by the transfectant included lysis of the TNF-sensitive murine L929 cell in coculture, secretion of TNF, and absence of nitrite synthesis. For the NO pathway controls included lysis of the murine P815 mastocytoma cocultured with activated EMT-6 cells that had been pretreated with murine rIFN-gamma and LPS, production of nitrite by this activated effector cell, and an absence of TNF secretion. The target cell panel included L929, EMT-6, P815, and murine B16 melanoma and TU-5 sarcoma cell lines. All targets on this panel were susceptible to lysis by LPS-triggered murine bacillus Calmette-Guerin-activated macrophages. The 3T3 transfectant caused significant lysis of cocultured L929 and TU-5 targets. The EMT-6 effector cell only caused significant lysis of the P815 target. When both effector cells were cocultured with these target cells, lysis of the P815 target was observed to be additive or superadditive; however, for all the other targets, cytotoxicity was comparable with or subadditive compared with that seen with the 3T3 transfectant effector cell alone. Thus, these two pathways do not appear to account for the broad, potent tumoricidal activity observed for activated macrophages in vitro. PMID- 1918994 TI - Free fatty acids are produced in and secreted from target cells very early in cytotoxic T lymphocyte-mediated killing. AB - Conjugation of CTL with their cognate targets elicits a number of early changes within the target cell that are thought to play an important role in the lytic mechanism. We now report that at times earlier than 5 min after conjugation with allospecific CTL, free fatty acids (FFA) are produced in and then secreted from alloantigen-bearing target cells. Using murine CTL clones with different alloantigen specificities, stimulation of FFA production from target cells was found to be Ag specific. FFA production does not appear to be specific for any particular FFA species. Indeed, a wide spectrum of cis unsaturated as well as saturated FFA are produced. FFA production is well correlated with, and specific for, CTL-mediated target cell lysis. Other means of perturbing or lysing target cells, including freeze/thaw disruption, detergent solubilization, or increasing membrane permeabilization with ionomycin, do not stimulate FFA production. In particular, FFA production is not stimulated by treatment with pore-forming granules under conditions that cause more than 90% target cell lysis. These results suggest that FFA production plays an important role in CTL-mediated lysis because stimulation of FFA release specifically requires an event that is CTL induced, occurs very early after conjugation, and is strongly correlated with CTL mediated lysis. PMID- 1918995 TI - Role of tumor-derived cytokines on the immune system of mice bearing a mammary adenocarcinoma. II. Down-regulation of macrophage-mediated cytotoxicity by tumor derived granulocyte-macrophage colony-stimulating factor. AB - Peritoneal elicited macrophages (PEM) from mammary tumor-bearing mice have a decreased capacity to become cytotoxic against syngeneic, allogeneic, and xenogeneic target cells upon in vitro stimulation with LPS, as compared with PEM of normal mice. A regulatory mechanism other than PG release is suggested because the addition of both indomethacin and LPS to macrophage cultures from tumor bearing mice caused no changes in their cytotoxic capability. Because tumor products have been implicated in the down-regulation of immune responses, we investigated whether pretreatment with supernatants from the tumor cell line DA 3, derived from the in vivo mammary adenocarcinoma D1-DMBA-3, affects the cytolytic capacity of macrophages. This treatment inhibits, in a dose-dependent fashion, the ability of stimulated normal PEM to kill target cells. Partial purification of DA-3 cell line supernatant showed that most of the inhibitory activity was exerted by factors with a molecular mass greater than 10 kDa and less than 30 kDa. However, slight inhibition could also be observed with fractions containing molecules less than 10 kDa. The data suggest that more than one factor released by the mammary tumor cells may be involved in the down regulation of macrophage-mediated cytotoxicity. Because the DA-3 cells constitutively produce granulocyte-macrophage CSF (GM-CSF), which has a molecular mass of 27 kDa, we pretreated PEM from normal mice in vitro with rGM-CSF for 24 h. This resulted in a dose-dependent decrease in their capacity to kill tumor target cells upon LPS stimulation. Furthermore, PEM from normal mice injected with rGM-CSF for 25 days displayed a profound decrease in their cytolytic ability against DA-3 targets upon in vitro stimulation with increasing amounts of LPS. The pretreatment of PEM from normal mice with a combination of DA-3 cell supernatants and specific anti-GM-CSF partially neutralized the inhibitory effect of the DA-3 supernatant on macrophage tumoricidal capability. These results indicate that tumor-derived GM-CSF is an important factor involved in the decreased macrophage cytotoxicity during mammary adenocarcinoma progression. PMID- 1918996 TI - Liposome-encapsulated antigens engender lysosomal processing for class II MHC presentation and cytosolic processing for class I presentation. AB - Liposome-encapsulated protein Ag were used to dissect the roles of various subcellular compartments in Ag processing for class I and class II MHC-restricted presentation. Macrophages exhibited efficient processing of Ag encapsulated in acid-resistant dioleoylphosphatidylcholine/dioleoylphosphatidylserine liposomes, which sequester their contents from potential endosomal processing events and release them only after delivery to lysosomes. Lysosomal processing was demonstrated for all four Ag studied (OVA, murine hemoglobin, bovine ribonuclease A, and hen egg lysozyme), establishing the recycling of immunogenic peptides from lysosomes after Ag processing. These acid-resistant liposomes did not engender class I processing. Ag encapsulated within acid-sensitive dioleoylphosphatidylethanolamine/palmitoylhomocysteine liposomes were also processed via the class II pathway. Of the four Ag encapsulated in liposomes, one, OVA, was tested for ability to stimulate a class I-specific response. OVA in acid-resistant liposomes did not engender a class I-specific response. In contrast, OVA encapsulated in acid-sensitive liposomes was presented by class I molecules, albeit less efficiently than it was presented by class II molecules. We interpret this to be the result of the release of a minor portion of the encapsulated Ag into the cytosol. PMID- 1918998 TI - Polyclonal B cell activation by the Eta-1 cytokine and the development of systemic autoimmune disease. AB - Studies of systemic autoimmune disease have led to the view that initiation and progression of the disease process reflects chronic and sustained B cell activation by unidentified polyclonal activating agents. In earlier studies, we found that T cells from MRL/1 mice, which develop murine lupus, express very high levels of a newly defined T cell cytokine, Eta-1. Inasmuch as chronic and sustained B cell stimulation by T cells is a cardinal feature of MRL/1 disease, we determined the effects of this cytokine on Ig production by B cells. We show that both recombinant and biochemically purified natural Eta-1 stimulate IgM and IgG production by mixtures of B cells and macrophages from the autoimmune MRL/l strain. Additional studies suggest that optimal Ig production by Eta-1 may require macrophages and reflect enhanced Ig production by large B cells. These findings support the view that elevated levels of endogenous Eta-1 may cause chronic and sustained polyclonal B cell activation that leads to autoimmune disease in this murine model. PMID- 1918997 TI - The HIV-1 gp120 envelope protein has the intrinsic capacity to stimulate monokine secretion. AB - Results and conclusions concerning the ability of HIV glycoprotein (gp) 120 to stimulate monokine secretion have been equivocal, based on observations using natural gp120 derived from infected human cells and a Chinese hamster ovary (CHO) cell-derived recombinant fusion protein. Current studies were designed to determine whether differences in recombinant gp120 proteins could result in failure to trigger monokine production. We found that natural gp120 could stimulate monocytes to release TNF-alpha, IL-1 beta, IL-6, and granulocyte macrophage-CSF, and this effect could be blocked with soluble CD4. Full-length rgp120 either expressed from an adenovirus vector and purified from infected human cells, or derived from CHO cells, could function similarly. In contrast, full-length recombinant envelope protein expressed in a baculovirus system and a CHO cell-derived recombinant fusion protein tested previously, consistently failed to stimulate monokine production. The stimulatory capacity of both natural and full-length CHO cell-derived gp120 was eliminated by heating at 100 degrees C, and could be blocked with excess CHO cell-derived gp120 fusion protein. Inasmuch as the baculovirus-expressed gp120 and the CHO cell-derived recombinant fusion protein can bind to CD4, these results suggest that HIV gp120 binding to CD4 on the monocyte surface may of itself be insufficient for stimulation of monokine secretion. Therefore, primary protein structure, as well as posttranslational protein modifications, may determine this activity. PMID- 1918999 TI - Recombinant gp120 specifically enhances tumor necrosis factor-alpha production and Ig secretion in B lymphocytes from HIV-infected individuals but not from seronegative donors. AB - The effect of recombinant protein from the envelope (gp120) of the HIV on B lymphocytes purified from either HIV-infected individuals or healthy seronegative controls was examined. B cells from peripheral blood and lymph nodes of HIV infected individuals spontaneously secreted TNF-alpha; this secretion was augmented by the presence of gp120, whereas B cells from healthy seronegative donors failed to secrete significant levels of TNF-alpha in the presence or absence of gp120. In a coculture system of B cells and chronically HIV-infected T cells (ACH-2), where viral expression is largely mediated by TNF-alpha, gp120 increased virus expression only if the B cells were obtained from HIV-infected individuals. The effects of gp120 on viral expression in this system were not mediated via CD4 receptor binding or FcR binding of anti gp120-gp120 immune complexes. Besides its effect on cytokine production, gp120 also stimulated Ig secretion in B cells from HIV-infected individuals, but not from normal donors. Finally, it was demonstrated by in situ hybridization that germinal centers of lymph nodes from HIV-infected individuals contain large amounts of HIV RNA that is in close proximity to germinal center B cells. These findings suggest that the hyperplastic germinal centers of lymph nodes provide an unique environment for virus expression and accumulation where gp120 stimulates B cells to secrete HIV inductive cytokines, such as IL-6 and TNF-alpha, and thereby further enhances virus expression in infected cells in a paracrine manner. PMID- 1919000 TI - Humoral immune functions in IL-4 transgenic mice. AB - We have analyzed mice expressing IL-4 as a transgene, and found that expression of this lymphokine has profound effects on B cell function. B cells from transgenic mice exhibit phenotypic changes, including an increase in size and elevated expression of class II MHC. IL-4 increases the quantity of IgE produced by transgenic-derived B cells in response to LPS stimulation. In vivo, IL-4 markedly affects the serum Ig isotype repertoire. Serum levels of IgG1 and IgE are elevated, and levels of IgG2a, IgG2b, and IgG3 are depressed in IL-4 transgenic mice. Ag-specific antibody responses to immunization with hapten carrier conjugates are also affected by IL-4. Transgenic mice show increased anti hapten IgE and IgG1 and reduced anti-hapten IgG2a, IgG2b, and IgG3, compared with wild-type mice. Ag-specific IgE is substantially induced by T cell-dependent Ag, but not T cell-independent Ag, suggesting that cognate T-B interactions in addition to IL-4 are required for generating IgE responses in vivo. In vivo treatment with the anti-IL-4 mAb 11B11 reverses many of the isotype alterations in the transgenic mice, indicating that these changes arise as a direct consequence of IL-4 secretion. PMID- 1919001 TI - IL-1-converting enzyme requires aspartic acid residues for processing of the IL-1 beta precursor at two distinct sites and does not cleave 31-kDa IL-1 alpha. AB - IL-1 converting enzyme (ICE) specifically cleaves the human IL-1 beta precursor at two sequence-related sites: Asp27-Gly28 (site 1) and Asp116-Ala117 (site 2). Cleavage at Asp116-Ala117 results in the generation of mature, biologically active IL-1 beta. ICE is unusual in that preferred cleavage at Asp-X bonds (where X is a small hydrophobic residue), has not been described for any other eukaryotic protease. To further examine the substrate specificity of ICE, proteins that contain Asp-X linkages including transferrin, actin, complement factor 9, the murine IL-1 beta precursor, and human and murine IL-1 alpha precursors, were assayed for cleavage by 500-fold purified ICE. The human and murine IL-1 beta precursors were the only proteins cleaved by ICE, demonstrating that ICE is an IL-1 beta convertase. Analysis of human IL-1 beta precursor mutants containing amino acid substitutions or deletions within each processing site demonstrated that omission or replacement of Asp at site 1 or site 2 prevented cleavage by ICE. To quantitatively assess the substrate requirements of ICE, a peptide-based cleavage assay was established using a 14-mer spanning site 2. Cleavage between Asp [P1] and Ala [P1']2 was demonstrated. Replacement of Asp with Ala, Glu, or Asn resulted in a greater than 100-fold reduction in cleavage activity. The rank order in position P1' was Gly greater than Ala much greater than Leu greater than Lys greater than Glu. Substitutions at P2'-P4' and P6' had relatively little effect on cleavage activity. These results show that ICE is a highly specific IL-1 beta convertase with absolute requirements for Asp in P1 and a small hydrophobic amino acid in P1'. PMID- 1919002 TI - IL-4-dependent IgE switch in membrane IgA-positive human B cells. AB - IgE responses by human B cells, separated according to membrane Ig classes, were analyzed in a clonal assay using EL-4 thymoma cells as helper cells, T cell supernatant, and rIL-4. In cultures seeded by means of the autoclone apparatus of the FACS, IgE responses were generated frequently by either IgM (mu+/gamma-alpha ) or IgA (alpha +/mu-)-positive B cells (16 and 14% of the Ig producing wells, respectively), but rarely by IgG (gamma +/mu-)-positive B cells (1.3% of Ig producing wells). The total amounts of Ig secreted by IgM-, IgG-, or IgA-positive cells and the total proportions of responding autoclone wells (23-27%) were comparable. All IgE secretion was IL-4 dependent. When the Ig secretion patterns from alpha +/mu- vs alpha +/mu-epsilon- B cells were compared, most autoclone wells from both types of cells produced IgA only, and similar proportions of IgA producing wells (6.2 and 6.0%) also secreted IgE. In addition, IgE restricted responses occurred 6 times more frequently with alpha +/mu- than with alpha +/mu epsilon- cells, which suggests that membrane IgA+E double-positive, IgE committed B cells occur in vivo. The isotype pattern generated by alpha +/mu-epsilon- B cells cannot be explained by a chance assortment of separate IgA and IgE precursors or by cytophilic antibody. Thus, IL-4 dependent switch to IgE occurred frequently in IgM- or IgA-positive, but rarely among total IgG-positive, B cells. This could be relevant to IgE production in mucosal tissues rich in IgA expressing B cells. PMID- 1919004 TI - Heterogeneous IgE glycoforms characterized by differential recognition of an endogenous lectin (IgE-binding protein). AB - IgE is highly glycosylated, but the function of the oligosaccharide side chains is largely unknown. The previous discovery of an animal lectin, IgE-binding protein (epsilon BP), affords an opportunity to study potential carbohydrate dependent effector functions of IgE. epsilon BP is a beta-galactoside-specific lectin with binding affinity for IgE and is now known to be equivalent to carbohydrate-binding protein 35 and the Mac-2 Ag; thus, it may have multiple functions in addition to IgE binding. We have previously shown that rat r epsilon BP recognizes sialidase-treated human myeloma IgE to a much greater extent than the untreated IgE. In contrast, human epsilon BP binds essentially equivalently to a monoclonal murine IgE with or without sialidase pretreatment. To validate a possible role for epsilon BP in the IgE system, we investigated the pattern of recognition of epsilon BP for various polyclonal human IgE samples. We show that polyclonal IgE derived from four individuals with hyper-IgE syndrome or atopic dermatitis recognizes epsilon BP and that there is individual variation in the proportion of IgE recognized by epsilon BP, ranging from greater than 60% for one sample to almost undetectable levels in another. We conclude that epsilon BP does indeed recognize polyclonal IgE and that this recognition is modulated by sialylation of IgE oligosaccharides. Furthermore, there exist different IgE glycoforms, varying in the degree of sialylation, and these are distributed in a distinct manner in different individuals. PMID- 1919003 TI - Amino acid residues 1101-1105 of the isotypic region of human C4B is important to the covalent binding activity of complement component C4. AB - The C4A and C4B isotypes of human C4 show certain functional differences that stem from their relative preference for transacylation to amino (-NH2) vs hydroxyl (-OH) nucleophiles, respectively, on complement-activating surfaces. Comparison of amino acid sequences of the alpha-chain fragment of C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 are the only consistent structural difference between isotype, i.e., Pro, Cys, Pro, Val, Leu, Asp in C4A and Leu, Ser, Pro, Val Ile, His in C4B. These residues may be responsible either in part or entirely for properties associated with isotype. To examine the functional role of residues 1101-1106 in C4B-mediated hemolysis, whole serum or immunopurified human C4 with allotypes, A3B1, A3, B2B1, or B1 were preincubated in the presence or absence of an antipeptide mAb (BII-1) specific for amino acid residues 1101-1105 of C4B. Sensitized sheep E and C4-deficient guinea pig serum was then added and lysis measured by absorbance at 415 nm. Our results show lysis of antibody-sensitized sheep E is inhibited by antibody and C4B2B1, C4B1, or C4A3B1 but not antibody and C4A3. The interference of hemolysis by BII-1 could not be explained by inhibition of activation of C4B or inhibition of C3 or C5 convertase activity. Furthermore, results from uptake experiments show that BII-1 interferes with the covalent binding activity of C4B, indicating residues 1101-1105 play a role in the covalent binding reaction of C4B to the target E-antibody complex. PMID- 1919005 TI - Characterization of the autoantigen calreticulin. AB - Anti-Ro/SS-A antibodies are commonly found in the sera of patients with Sjogren's syndrome and SLE. These antibodies also occur in the mothers of children with neonatal lupus and congenital heart block. Ro/SS-A is a ribonucleoprotein complex whose cellular function remains unknown. To study its cellular function and to characterize its immunoreactivity, we have used an oligonucleotide designed after the published amino terminal sequence of a putative 60-kDa Ro/SS-A autoantigen to isolate its cDNA. This cDNA encodes a polypeptide that is the human homologue of calreticulin, a calcium binding protein of the endoplasmatic reticulum. The encoded polypeptide also shows a 64.4% identity with RAL-1, an Ag of the river blindness pathogen Onchocerca volvulus. Contrary to the data published by other authors, our results indicate that calreticulin is not a Ro/SS-A autoantigen. Moreover, we show that anticalreticulin autoantibodies occur in the sera of patients with SLE and patients with onchocerciasis. PMID- 1919006 TI - Potentiation of tumor necrosis factor-alpha-mediated cytotoxicity of mast cells by their production of nitric oxide. AB - Nitric oxide (NO or endothelium-derived relaxing factor) has many of biologic actions, including the maintenance of blood pressure, inhibition of platelet aggregation, and cytotoxicity by phagocytic cells. Several cell types produce NO from L-arginine. Given recent emphasis on mast cell (MC)-dependent TNF-alpha mediated cytotoxicity, we investigated the role of NO in rat peritoneal MC (PMC) and intestinal mucosal mast cell-mediated cytotoxicity. MC cytotoxicity against the TNF alpha-sensitive target, WEHI-164, was potentiated by L-arginine. The NO competitive inhibitors, N omega-nitro-L-arginine and NG-methyl-L-arginine, diminished the cytotoxicity of rat PMC by 27 and 17%, respectively. However, hemoglobin, which binds to NO, inhibited the cytotoxic activity of PMC by 49% in the presence of 1 mM L-arginine and by 24% in L-arginine-free medium. The latter suggests that PMC use intracellular stores of L-arginine to produce NO. Neither hemoglobin nor NO metabolites affected human rTNF-alpha cytotoxicity. Furthermore, sodium nitroprusside, with its free radical NO group, restored PMC cytotoxicity in L-arginine-free medium to the level observed in 1 mM L-arginine medium. Studies with a platelet aggregation bioassay and various NO inhibitors confirmed that PMC produce NO. In addition, increased levels of NO2- were observed in medium of A23187, TNF-alpha, or WEHI-164-stimulated PMC. PMID- 1919007 TI - Accumulation of indigestible substances reduces fusion competence of macrophage lysosomes. AB - It is well known that mouse macrophages loaded with indigestible substances become highly vacuolated. However, why this vacuolization occurs and its effect on lysosome function and intracellular transport during endocytosis remain unknown. Here, macrophage vacuoles were formed by incubation with sucrose or a tripeptide of the D-isomer of alanine and were determined to be lysosomal in origin by staining with the lysosomal glycoproteins and lysosomal hydrolases. However, as indicated by confocal and electron microscopy, subsequent delivery of both fluid phase (lucifer yellow, horse-radish peroxidase) and receptor-bound ligands (IgG complexes) was significantly reduced, suggesting that indigestible material reduced the ability of the loaded lysosomes to fuse with endosomes containing newly internalized tracers. Nevertheless, ligands internalized by the vacuolated cells were degraded at almost the normal rate, indicating that degradation occurs in the absence of delivery to the loaded lysosomes. We have also found that this fusion inhibition occurs in human alveolar macrophages loaded with physiologic debris from smoking and asbestos. These results suggest that indigestible material within lysosomes, such as is present in residual bodies in vivo, may affect their fusion competence. PMID- 1919008 TI - Antiviral immune responses of fully allogeneic irradiation bone marrow mouse chimeras. AB - In (B10.BR----B10) chimeras infected with lymphocytic choriomeningitis (LCM) virus higher titers were attained in spleens and livers than in organs of the mice used for their construction, and the subsequent elimination was retarded, but eventually the virus was cleared. The numbers of LCM virus-specific CTL and their precursors as quantitated with chromium-release assay and limiting dilution method, respectively, were lower in chimeras than in B10.BR or C57BL/10J mice, and fewer were restricted for the haplotypes of the donors than of the recipients. The same was true with regard to antiviral effector cells, which were determined by adoptive immunization. The numbers of spleen cells releasing IgM and IgG antiviral antibodies were virtually as high in chimeras as they were in C57BL/10J and B10.BR mice. Transfer of immune splenocytes from either B10.BR or C57BL/10J mice resulted in incomplete virus elimination from the spleens of infected chimeras, whereas injection of a mixture of the two types of immune cells led to efficient clearance. We conclude that in the chimeras cells of both donor and recipient haplotypes participate in the infection, which is terminated by H-2k- and H-2b-restricted T lymphocytes that these animals are capable of generating. We conclude, furthermore, that clearance of the LCM virus from the tissues requires contact between effector and target cells. PMID- 1919009 TI - The involvement of tumor necrosis factor in immunity to Salmonella infection. AB - The role of TNF in immunity to Salmonella in mice was studied. Antiserum specific for murine TNF was raised and used to neutralize TNF activity in vivo. Injection of this serum into mice infected with the moderately mouse virulent Salmonella typhimurium strain M525 caused exacerbation of disease. Such treatment had no effect on the course of an infection with an attenuated S. typhimurium aroA (strain SL3261) mutant. However, the protection afforded by immunisation with live SL3261 against challenge with the virulent parent strain (SL1344) was abolished by anti-TNF antiserum. Interestingly both early (3 wk) immunity and late (10 wk) immunity was neutralized by such treatment. Inasmuch as early immunity is considered to be nonspecific and macrophage-mediated while late immunity is considered to be serotype-specific and T cell mediated, this suggests that TNF plays a role in protection from Salmonellosis in both cases. PMID- 1919010 TI - Utilization of V kappa families and V kappa exons. Implications for the available B cell repertoire. AB - A molecular cloning approach was used to determine the relative utilization of 2 individual V kappa 21 genes, 13 V kappa gene families, and the 4 functional J kappa gene segments among splenic B cells of nonimmunized BALB/c mice. Based on the observed frequency of individual V kappa gene expression, we estimate that the mouse genome encodes 150 to 180 functional V kappa genes, and we suggest that most functional V kappa exons are expressed at comparable frequencies in the preimmune antibody repertoire. In contrast, clear differences in J kappa segment utilization were observed, J kappa 4 being consistently underrepresented with respect to the other J kappa segments. PMID- 1919011 TI - Cloning of the cDNA for the serine protease homolog CAP37/azurocidin, a microbicidal and chemotactic protein from human granulocytes. AB - Human cationic antimicrobial protein (CAP37) is a neutrophil granule protein with monocyte chemotactic and antibacterial activity. A CAP37 cDNA clone of 899 bp was isolated from an HL-60 cDNA library using degenerate oligonucleotide probes based on partial N-terminal sequence of the CAP37 protein. The cDNA sequence predicts an open reading frame of 753 bp encoding a protein of 251 amino acids. A 26 residue eukaryotic signal peptide and a potential 7 amino acid pro-peptide are present at the N-terminus of the protein. The cDNA sequence also predicts three N linked glycosylation attachment sites and eight intramolecular cysteines. The deduced amino acid sequence of CAP37 shows 44, 42, and 32% homology at the amino acid level to neutrophil elastase, myeloblastin, and cathepsin G, respectively, suggesting that CAP37 is a member of the serine protease gene family. CAP37 does not possess serine protease activity probably due to mutations in two of three residues in the catalytic triad of the "charge relay system." Whereas CAP37 is expressed in undifferentiated HL-60 cells no message is detected in mature neutrophils. PMID- 1919012 TI - NKR-P1, an activating molecule on rat natural killer cells, stimulates phosphoinositide turnover and a rise in intracellular calcium. AB - NKR-P1 is a 60-kDa homodimer expressed on all rat NK cells. Previous studies by others suggest that NKR-P1 may play a role in NK cell activation because antibody to NKR-P1 stimulates the release of granules from NK cells, and anti-NKR-P1 causes redirected lysis by activated NK cells against targets that express FcR. To examine the mechanism of transmembrane signaling by NKR-P1, we studied the rat NK cell line, RNK-16. We here demonstrate that F(ab')2 antibody to NKR-P1 stimulates phosphoinositide turnover and a rise in intracellular calcium within RNK-16 cells. The response is augmented by cross-linking the F(ab')2 antibody. The phosphoinositide/calcium pathway is also stimulated by NKR-P1 in activated rat NK cells, although no response is detectable in polymorphonuclear cells, which also express NKR-P1. We also demonstrate that RNK-16 cells kill the anti NKR-P1 (3.2.3) hybridoma and that exposure to the hybridoma target cells stimulates phosphoinositide turnover in RNK-16 cells. Both killing and phosphoinositide turnover are inhibited by F(ab')2 anti-NKR-P1, implicating NKR P1 in both responses. In contrast, neither cytotoxicity nor phosphoinositide turnover is appreciably blocked by F(ab')2 anti-NKR-P1 in response to YAC-1 targets. Thus, with either target, killing is linked to phosphoinositide turnover, but killing of YAC-1 involves pathways that differ from those that direct killing of the anti-NKR-P1 hybridoma. Our studies support the hypothesis that NKR-P1 may serve as an activating cell-surface receptor on NK cells, and they clarify the mechanisms by which it activates NK cells. PMID- 1919013 TI - Tumor rejection antigens on BALB3T3 cells transformed by activated oncogenes. AB - The clonal expression of tumor rejection Ag (TRA) was analyzed on nine different clones derived from parental BALB3T3 cells that were transfected with activated H ras, polyoma middle T (PyMT), c-myc, and v-src oncogenes. It was shown that Bras h clone, which is an activated H-ras oncogene-induced transformant, expressed TRA as assessed in the transplantation study using syngeneic BALB/c mice. This TRA was not detected on parental BALB3T3 nontransformed cells, suggesting that TRA could be expressed in the BALB3T3 cell transformation. Furthermore, the cross protection experiments indicated that this TRA was also conferred on other BALB3T3 transformants with high anchorage-independent growth potential such as an activated H-ras transformant Bras-d, and PyMT transformants BMT-f, BnMT-11, BnMT 20, except in the case of one H-ras transformant Bnr-12. In contrast, this TRA was not expressed on the transfectants with little or no anchorage independent growth potential such as a PyMT transfectant BnMT-4, a c-myc transfectant Bmyc-7, and a v-src transfectant Bsrc-7. We developed the mAb BRH19 that could react with TRA+ clones but not with TRA- clones. This mAb makes an immunoprecipitate, which is composed of a 50-kDa single polypeptide chain from Bras-h cell lysate. An injection to mice with this antigen could confer the protection against Bras-h challenge. These data indicate that the 50-kDa putative TRA molecule could be expressed in close association with the cell transformation, irrespective of the introduced oncogenes, and there may exist some regulatory mechanisms rather than individually distinct manners for the expression of TRA. PMID- 1919014 TI - The international standards for interleukin-1 alpha and interleukin-1 beta. Evaluation in an international collaborative study. AB - Three ampouled preparations of interleukin-1 alpha (IL-1 alpha) and three ampouled preparations of interleukin-1 beta (IL-1 beta) were evaluated by 13 laboratories in six countries for their suitability to serve as international standards for these materials. The preparation were assayed in in vitro and in vivo bioassays, radioreceptor assays and immunoassays. On the basis of the results reported here, with the agreement of participants in the study and with the authorization of the Expert Committee on Biological Standardization (ECBS) of the World Health Organization (WHO), one of the preparations of IL-1 alpha and one of the preparations of IL-1 beta were established as international standards for these materials. Further, since the relative activities of IL-1 alpha and IL 1 beta were dependent upon the assay systems used, it was decided that reference should be made to units of IL-1 alpha activity or IL-1 beta activity rather than to IL-1 activity. PMID- 1919015 TI - Live attenuated Salmonella vaccines and their potential as oral combined vaccines carrying heterologous antigens. AB - Live attenuated salmonellae are protective, and are candidate vaccines against invasive salmonella infections in man and animals. Different attenuating mutations have been described, and more than one can be incorporated in a vaccine for added safety. Combined salmonella vaccines express target carbohydrate and protein antigens or epitopes from viruses, bacteria and eukaryotic parasites, either within or on the surface of the cell, as capsules, fimbriae, or in the flagellin. Humoral, secretory and cellular responses to the recombinant antigens has been demonstrated. Experimental protection against diseases including streptococcal infection, tetanus, influenza and malaria has been obtained. PMID- 1919016 TI - Evaluation of a solid-phase cellular enzyme immunoassay for detection of the serologically defined male antigen. AB - An indirect cellular enzyme immunoassay for the detection of the serologically defined male-specific antigen, SDMA, was developed using mouse spermatozoa as the target. Serum from B6 female mice injected with male spleen cells was used as the source of SDMA-specific antibody. Our results indicate that the assay is highly reliable (96% accurate) with an intra- and interassay coefficient of variation less than 12%. Since this assay is non-subjective and simple to perform it provides a useful alternative to the complement-dependent cytotoxicity assay for detection of SDMA. PMID- 1919017 TI - Quantitation of lymphocyte mediated sheep red blood cell hemolysis, using an ELISA reader. PMID- 1919019 TI - Macrophage phagocytosis: use of fluorescence microscopy to distinguish between extracellular and intracellular bacteria. AB - One of the challenges of phagocytosis research is to differentiate bacteria adherent to a host cell from bacteria which the cell has internalized. To address this question, various techniques such as fluorescence microscopy, electron microscopy, and flow cytometry have been used. We have adapted a flow cytometric method (Fattorossi et al., 1989) to use fluorescence microscopy for studying phagocytosis of fluorescein-labeled Listeria by inflammatory mouse peritoneal macrophages. In this assay, ethidium bromide is used as a quenching agent and is added to cells after they have phagocytosed labeled bacteria. Ethidium bromide causes extracellular FITC-labeled Listeria to fluoresce red-orange, whereas intracellular bacteria are not exposed to the dye and remain green. This process allows distinction between intracellular and extracellular bacteria by simultaneous visualization of both populations. PMID- 1919018 TI - Immunization strategies for the production of rat monoclonal anti-idiotope antibodies. AB - Anti-idiotypic antibodies are powerful reagents for the study of immunoregulation, and have potential interest as vaccines against tumors and infectious diseases. Three immunization strategies for the production of rat monoclonal anti-idiotope antibodies have been compared in this paper. Male Wistar rats were immunized i.p. and at multiple subcutaneous sites with 750 micrograms of purified monoclonal antibody against Plasmodium falciparum for three times and subsequently boosted by (1) intraperitoneal injection with 750 micrograms of the immunogen, (2) intravenous inoculation with 400 micrograms of the IgG, and (3) intrasplenic immunization with 200 micrograms of the idiotype. With the intraperitoneal boost method, the frequency of hybrids with anti-idiotope activity was 0.3-0.9% with 62.8-85.2% of the seeded wells containing hybrids. In the intravenous boost group, the percentage of hybrids demonstrating anti idiotope activity increased to 11.0-13.3% with 80.2-97.9% of the hybrid efficiency. When immunized by the intrasplenic boost route, the frequency of anti idiotope hybrids generated rose to 12.9-16.4% with 82.3-96.6% of the hybrid efficiency. There was no obvious effect of the boost immunizing methods on the generation of rat monoclonal anti-mouse IgG antibodies. These results indicated that the multiple-site immunization followed by intravenous or intrasplenic boost injection was an appropriate immunizing method for the production of monoclonal anti-idiotope antibodies. PMID- 1919020 TI - A rapid FPLC method for purification of the third component of human and guinea pig complement. AB - A method is described for the purification of human and guinea pig C3 from small amounts of serum. This procedure requires only two steps--polyethylene glycol (PEG) precipitation and fast protein liquid chromatography (FPLC) Mono Q HR 10/10 ion exchange chromatography. The protocol takes less than two hours to complete and yields 4-6 mg of purified C3. Similar results, in terms of antigenic and functional recovery, were obtained for both human and guinea pig components. About 67% of C3 antigen was recovered from eluted fractions with fully preserved specific activity. Isolated C3 was over 95% pure as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography; this level of purity was confirmed by the absence of any observable contamination as assessed by immunoelectrophoresis using high titer anti-whole human serum. This method allows rapid and reproducible purification of fully active human or guinea pig C3 on a daily basis. PMID- 1919021 TI - Immunoassay to measure staphylococcal protein A in the presence of murine immunoglobulins. AB - Immunoassays designed to measure low concentrations of staphylococcal protein A are subject to varying degrees of interference by excess IgG. We have developed an enzyme-linked immunosorbent assay (ELISA) that overcomes this problem by analyzing IgG-containing protein A samples in solutions buffered at pH 3.5. Under these carefully selected conditions, protein A is absorbed efficiently by solid phase chicken anti-protein A antibodies, but protein A-IgG complexes are largely dissociated. The assay has a protein A detection limit of 0.1 ng/ml, and the response is unaffected by 0.25 mg/ml murine IgG. The method should be useful for determining protein A contamination levels in antibodies purified by affinity chromatography on immobilized protein A resins. PMID- 1919022 TI - Extraction and differentiation of the Su autoantigen from calf thymus nuclei. AB - Antibodies to Su antigen have been reported previously as a distinct antigen antibody system associated with connective tissue diseases; most specifically systemic lupus erythematosus and undifferentiated connective tissue disease. The Su antigen was first identified by double immunodiffusion using calf thymus nuclear extract (CTNE) as a source for Su antigen. In this report, enhanced extraction of Su antigen was achieved using deoxyribonuclease I (DNase) for preparation of CTNE. Only the Sm antigen was found in comparable quantities in the DNase CTNE. Western immunoblotting and immunoprecipitation employing DNase CTNE and extracts of [35S]methionine-labeled HeLa cells respectively were used for further characterization and differentiation of the Su antigen. Sera from patients positive for Su antibodies by double immunodiffusion were found to react most specifically with antigen components in a molecular weight range of approximately 50-55 kDa. These methods should assist in further understanding the biochemical properties of the Su antigen. PMID- 1919023 TI - Behavior in immunoblotting of dimeric and monomeric forms of nonspecific cross reacting antigen (NCA-50) from normal lung. AB - The dimeric and monomeric forms of NCA-50 from normal lung showed differences in binding to nitrocellulose in an immunoblotting procedure. The NCA dimer showed weaker binding, it passed through nitrocellulose and was more easily washed out from the blot. The NCA monomer was bound strongly and was detected with higher sensitivity following immunoblotting. PMID- 1919024 TI - Immunoturbidimetric assay of beta 2 microglobulin using latex particles in microplates. AB - A latex particle immunoturbidimetric assay in microplates has been developed for the quantitation of beta 2 microglobulin. The assay which involves three pipetting steps and one incubation, has a clinically useful range of 0.4-16 mg/l. A comparison of the method with a commercial radioimmunoassay in the analysis of 125 sera revealed a high degree of correlation. Although the assay was performed manually, it showed considerable potential for full automation. PMID- 1919025 TI - Quenching of intracellular autofluorescence in alveolar macrophages permits analysis of fluorochrome labelled surface antigens by flow cytofluorometry. AB - We report a new technique in which the autofluorescence of alveolar macrophages from smokers is quenched by crystal violet. This technique permits immunostaining of surface antigens of these cells and enables the stained cells to be analysed by flow cytofluorometry. The variable solubility of crystal violet makes it important to characterize the crystal violet solution by its quenching properties and not rely on the assumed concentration of dissolved dye. High concentrations of crystal violet lowered the number of cells and gave a decreased amount of surface antigen (CD11b). However, a lower concentration of crystal violet could be used if the cells were fixed with paraformaldehyde (4%) and the membranes were permeabilized with n-octyl-beta-D-glucopyranoside (0.6%). Using a phagocytic model with FITC-conjugated particles we were able to show that this treatment gave an efficient permeabilization of phagolysosomal membranes. PMID- 1919026 TI - Simultaneous flow cytometric detection of antibodies against platelets, granulocytes and lymphocytes. AB - We present a time-saving and objective flow cytometric immunofluorescence assay for the simultaneous detection of antibodies against platelets, granulocytes or lymphocytes using a reconstituted mixture of these cell populations. Platelets, granulocytes and lymphocytes could be distinguished on the basis of their forward (FSC) and sideways (SSC) light scattering properties plotted on scales of 4 log orders. After setting FSC/SSC gates around the platelets, granulocytes and lymphocytes, the reactivity of the sera with the cell populations was determined by histogram analyses of immunofluorescence for each gate. The flow cytometric assay of reconstituted cell mixtures showed a strong, positive correlation with a reference microscopic immunofluorescence assay of separate cell suspensions. The reproducible procedures for the isolation and staining of the cells and the electronic stability of the flow cytometer permitted the use of the same gate and marker settings throughout the experiments. Consequently, the entire analysis of data stored in list mode could be performed using a keystroke, so that time consuming and subjective manual analyses were avoided. PMID- 1919027 TI - Pitfalls in the quantitative estimation of the secretion of granule proteins by eosinophils. AB - The secretion of preformed granule proteins by eosinophils is an important correlate of eosinophil activation. However, a review of the literature reveals large disparities in the amounts of these substances which were reportedly secreted when eosinophils were activated. In the present study we report that our attempts to quantitate the secretion of eosinophil peroxidase and eosinophil derived neurotoxin from activated eosinophils by measuring these substances in the incubation supernatants were uniformly unsuccessful. We found that, once they were secreted, both eosinophil peroxidase and eosinophil-derived neurotoxin were promptly lost to assay and presumably destroyed. Thus the measurement of the difference in the concentration of these substances in eosinophils prior to and after activation, revealed that as much as 65% of the eosinophil-derived neurotoxin and 62% of the peroxidase in the eosinophils were lost to assay during activation of the cells whereas the largest amount of these substances which could be measured in the incubation supernatants never exceeded 2%. Evidence is presented that the destruction of eosinophil-derived neurotoxin must occur prior to the release of this substance into the medium. Attempts to inhibit the destruction of eosinophil peroxidase and of eosinophil-derived neurotoxin by incorporating various inhibitors into the incubations were unsuccessful. These results emphasize the need to monitor the overall recoveries of secreted products from activated eosinophils and suggest that meaningful estimates of the secretion of these granule proteins from activated eosinophils can only be obtained by measuring the residual content of these substances in eosinophils after they have been activated and comparing these values to the contents of eosinophils prior to activation. PMID- 1919028 TI - Direct sequencing of variable HLA gene segments after in vitro amplification and allele separation by temperature-gradient gel electrophoresis. AB - Previously unrecognized variants of human leukocyte antigens (HLA) are currently being analyzed by in vitro amplification and sequencing of the variable gene segments. In heterozygous individuals, molecular cloning is required to separate the two concomitantly amplified haplotypic gene segments. A method is presented which facilitates the procedure of separating the two haplotypic gene segments by using a temperature-gradient gel electrophoresis (TGGE). The procedure comprises PCR amplification of the variable HLA gene segments, allele separation by TGGE, re-amplification of each of the separated allelic segments, and direct DNA sequencing using the PCR primers. PMID- 1919029 TI - An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. AB - A new tetrazolium salt XTT, sodium 3'-[1-[(phenylamino)-carbonyl]-3,4 tetrazolium]-bis(4-methoxy-6- nitro)benzene-sulfonic acid hydrate, was evaluated for use in a colorimetric assay for cell viability and proliferation by normal activated T cells and several cytokine dependent cell lines. Cleavage of XTT by dehydrogenase enzymes of metabolically active cells yields a highly colored formazan product which is water soluble. This feature obviates the need for formazan crystal solubilization prior to absorbance measurements, as required when using other tetrazolium salts such as MTT. Bioreduction of XTT by all the murine cells examined was not particularly efficient, but could be potentiated by addition of electron coupling agents such as phenazine methosulfate (PMS) or menadione (MEN). Optimal concentrations of PMS or MEN were determined for the metabolism of XTT by the T cell lines HT-2 and 11.6, NFS-60 a myeloid leukemia, MC/9 a mast cell line and mitogen activated splenic T cells. When used in combination with PMS, each of these cells generated higher formazan absorbance values with XTT than were observed with MTT. Thus the use of XTT in colorimetric proliferation assays offer significant advantages over MTT, resulting from reduced assay time and sample handling, while offering equivalent sensitivity. PMID- 1919030 TI - Suspended mouse peritoneal macrophages. Preparation and properties. AB - Since macrophages (MPH) are able to adhere firmly to solid surfaces, the recovery of viable and functional MPH has proven to be extremely difficult. We have developed a simple method using agarose coating for preparing MPH and culturing the cells in suspension. Their properties were tested over 72 h. The oxidative burst declined with time, but could be restored using the lymphokine rich supernatant of pokeweed-stimulated mouse spleen cells. In contrast, phagocytosis and Candida intra-cellular killing remained unchanged. PMID- 1919031 TI - Protein A-streptokinase fusion protein for immunodetection of specific IgG antibodies. AB - The streptococcal streptokinase gene truncated at its 5' end was fused to regions of the staphylococcal protein A gene encoding the Fc-binding domains A and B. The resultant fusion gene, when expressed in the Escherichia coli lacPO system or under the speA expression/secretion signals in S. sanguis, specified a bifunctional hybrid protein, SPA-SKC, capable of Fc binding and plasminogen activation. When used in immunoassays designed to titrate antisera raised against bovine chymosin, human serum albumin and fibrinogen, the assay using SPA-SKC compared well with that using a commercial SPA-enzyme conjugate. The simple preparative method together with its efficacy and ease of use, make SPA-SKC a potentially valuable detector reagent in quantitative immunology. PMID- 1919032 TI - Quantitative evaluation of indirect ELISA. Effect of calmodulin antagonists on antibody binding to calmodulin. AB - A simple linearization procedure has been developed to determine the apparent dissociation constant of the interaction between antigen and antibody from the data of indirect, non-competitive enzyme-linked immunosorbent assays (ELISA). Applying this dissociation constant the binding constant of ligands to antigen can be determined and the quantitative evaluation of the competitive ELISA experiments makes it possible to analyse the affinity of antibody to antigen on the surface and in solution. The binding of the monospecific anti-calmodulin antibody to calmodulin and to solid-phase bound calmodulin has been tested by non competitive and competitive assays. We have developed an experimental system where binding of the antibody to the solid-phase bound calmodulin has been studied under equilibrium conditions. Competitive ELISA experiments showed that the affinity of antibody to calmodulin on the surface and in solution was almost the same. The binding constant of a hypothalamic neuropeptide to calmodulin was determined using the quantitative ELISA approach. The neuropeptide was found to be of very high inhibitory potency (Kd = 2 nM) and competed with the antibody for calmodulin binding. This simple and sensitive procedure is suitable for screening molecules with anti-calmodulin activity and comparing their efficacy. PMID- 1919034 TI - The effects of incubation temperature and coating procedure on the measurement of antibodies to cardiolipin. AB - Many laboratories have established ELISAs for the the routine detection of anti cardiolipin antibodies (ACA). Earlier studies had indicated that assay incubation at 37 degrees C may interfere with the antigen binding capacity of these antibodies. We have reexamined this phenomenon by comparing ACA titers obtained when incubations are performed at either 37 degrees C or at room temperature (RT). In addition, the effect of coating antigen in aqueous or organic solution was compared. The sera tested included a set of recognized ACA standards and samples from 19 patients with SLE, two with primary anti-phospholipid syndrome, 71 patients with a variety of autoimmune and non-autoimmune disorders and 210 blood bank controls. The results show that while some sera do perform better under either incubation temperature there was no correlation between ACA titers and incubation temperature on a population basis either for IgG or IgM isotypes. This was seen both for positive standards and patient sera. For IgG ACA a similar phenomenon was seen if the microplates were coated with cardiolipin either in sodium carbonate or ethanol. For IgM ACA there was a significant increase in ACA titers at RT when cardiolipin was coated in ethanol. The data suggest that for most sera neither the antigen coating medium nor the assay incubation temperature are important variables in the determination of IgG ACA. Factors contributing to the influence of either variable in individual sera could not be identified. PMID- 1919033 TI - A monoclonal antibody-based enzyme immunoassay for quantitation of human tumor necrosis factor binding protein I, a soluble fragment of the 60 kDa TNF receptor, in biological fluids. AB - Three hybridoma cell lines secreting monoclonal IgG antibodies specific for human tumor necrosis factor-binding protein I (TNF-BP I), the extracellular domain of the 60 kDa TNF receptor, were developed by fusion of spleen cells from mice immunized with TNF-BP I purified from urine. The antibodies recognize three different epitopes on TNF-BP I. Two of the antibodies were used to develop a two site ('sandwich') enzyme immunoassay with horseradish peroxidase as the marker enzyme. The assay was able to measure TNF-BP I in serum, urine and cell culture supernatants with a sensitivity of about 200 ng/l and a precision better than 10%. TNF-BP I was detected in the serum of healthy individuals at a mean concentration of 2.1 +/- 1.0 micrograms/l (mean +/- standard deviation; range, 0.52-5.4 microgram/l, n = 42); no significant difference was seen in patients with chronic polyarthritis (2.3 +/- 0.79 micrograms/l; n = 15). Serum TNF-BP I was significantly elevated in patients with burns (6.5 +/- 1.7 micrograms/l; n = 10) and markedly increased in patients with renal failure (49 +/- 17 micrograms/l; n = 6). TNF-BP I was also detectable in urine from normal individuals (2.2 +/- 1.2 micrograms/l; range 0.78-4.3 micrograms/l; n = 16). Culture supernatants of several human tumor cell lines also contained TNF-BP I. The assay will be a useful tool to detect activation of the TNF receptor by the physiological ligands, TNF-alpha and TNF-beta, as well as transmodulation by other mediators in various pathological conditions. PMID- 1919035 TI - Lymphokine-activated killer cells: determination of their tumor cytolytic capacity by a clonogenic microassay using agar capillaries. AB - A lymphokine activated killer (LAK) cell assay has been developed using a clonogenic microassay in agar-containing capillaries with KB tumor target cells. The assay avoids the problems of the commonly used 51Cr release assay and mimics physiological conditions more closely. The assay procedure has been optimized, resulting in the following conditions: LAK cells are generated by incubating nonadherent peripheral blood mononuclear cells from normal donors with 20 U/ml interleukin-2 for 3 days and cocultivated with 10(4) KB human squamous carcinoma cells/ml at 5:1, 10:1, and 20:1 effector:target ratios for 24 h. The cocultivation mixture is then seeded into agar-containing glass capillaries, allowing undamaged tumor cells to form colonies. The colony number is proportional to the number of tumor cells seeded. The present microassay requires up to 90% less cells and agent quantities compared with other clonogenic assays. It thus provides a useful tool to quantitate LAK cell activity and its alteration by immunomodulatory agents. PMID- 1919036 TI - A comparison of the sensitivity and specificity of enzyme immunoassays and time resolved fluoroimmunoassay. AB - Time-resolved fluoroimmunoassay (TR-FIA) and various enzyme immunoassays (EIA) were compared in order to determine the detection system which showed the greatest degree of sensitivity without sacrificing specificity. The system chosen for the evaluation of these assays was the detection of antibodies to human immunodeficiency virus (HIV). For EIA, horseradish peroxidase (HRP) and alkaline phosphatase (AP) were investigated, each with a number of different substrates. HRP with its fluorogenic substrate, 3-(p-hydroxyphenyl)propionic acid (HPPA) was 1.6 times (p less than 0.01) more sensitive than with 3,3',5,5' tetramethylbenzidine (TMB) and four times (p less than 0.001) more sensitive than with 2,2'-azino-di(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS). AP with its fluorogenic substrate, 4-methylumbelliferyl phosphate (4MeUP), was 6-7 times (p less than 0.001) more sensitive than with phenolphthalein monophosphate (PMP) and 8-13 times (p less than 0.001) more sensitive than with p-nitrophenyl phosphate (pNPP). TR-FIA with Eu3(+)-labelled anti-human IgG was equivalent in sensitivity to HRP with TMB and AP with 4MeUP. PMID- 1919037 TI - C-reactive protein measured in dried blood spots from patients with cystic fibrosis. AB - There was no significant difference in C-reactive protein concentration determined in paired serum and eluates from dried blood spots collected on Guthrie cards; mean difference 0.6 microgram/ml (95% CI -3.3-2.2 micrograms/ml; n = 101). Dried blood spot samples were stable for up to 21 days and were unaffected by posting to the laboratory. In eight patients with cystic fibrosis undergoing specific antibiotic treatment for Pseudomonas aeruginosa pulmonary infection the fall in C-reactive protein concentration was not significantly different between serum and dried whole blood spot specimens. This method could be used to monitor infection and the response to antibiotic treatment. PMID- 1919038 TI - Quantitation of Hsp70 in tissues using a competitive enzyme-linked immunosorbent assay. AB - A competitive enzyme-linked immunosorbent assay has been developed to quantitate the Hsp70 levels in bovine tissues. Antibodies that show specificity to the low molecular weight form of Hsp70 (72 kDa) were developed in chickens, isolated from egg yolks, and characterized using Western blotting. Using this assay, we were able to verify quantitatively the previous observation that the low molecular weight form of Hsp70 exists at elevated levels in bovine skeletal muscle. Also, we report that the skeletal muscle contains the majority of the Hsp70 in the sarcoplasm, but a small amount of Hsp70 is localized in the sarcoplasmic reticulum. The amount of Hsp70 in bovine skeletal muscle is not at a maximal level because it can be increased by heat stress. The reliability, specificity, and use of enzyme-linked antibodies instead of radioactive materials make this assay preferable over previous quantitation techniques. PMID- 1919039 TI - A sandwich enzyme-linked immunosorbent assay for human interleukin-5. AB - A sandwich enzyme-linked immunosorbent assay (ELISA) was developed for human interleukin-5 (hIL-5) using a combination of monoclonal anti-recombinant(r)-hIL-5 antibody and rabbit anti-r-hIL-5 IgG. Detection limit of this assay was estimated to be 7.8 pg/ml, which was about 10,000 times more sensitive than that of the bioassay using BCL1 cells of murine origin. This ELiSA was specific for hIL-5, showing no crossreactivity to recombinant human GM-CSF, IL-4, TNF-alpha, IFN gamma and mouse IL-5 (mIL-5). The presence of 10% fetal calf serum did not interfere with the measurement of r-hIL-5. Coefficients of variation in intra assay and interassay were 1.1-4.6% and 2.3-11.3%, respectively. These results indicate that this assay system can be quite useful in quantifying hIL-5 in various biological fluids. PMID- 1919040 TI - Gene amplification by polymerase chain reaction in dermatology. AB - The polymerase chain reaction (PCR) is another new powerful technique in molecular biology that has begun to open new perspectives in modern science and also in dermatology. This brief report will therefore elucidate the general principles of the polymerase chain reaction, as well as its limitations and possible pitfalls. Furthermore an overview will be provided on the impact of PCR on molecular biologic approaches in oncology, immunology, and human genetics. The use of the method as a tool to detect microorganisms particularly viruses and bacteria, in cutaneous tissue and it potential other future applications are described as well. Because PCR is automated and is being more and more established in routine laboratories, physicians and scientists should be familiar with the basic principles and potential uses of this methodology. PMID- 1919041 TI - Ultrastructural similarities between epidermal Langerhans cell Birbeck granules and the surface-connected canalicular system of EDTA-treated human blood platelets. AB - Birbeck granules characterize under the electron microscope epidermal Langerhans cells. These distinctive pentalaminar organelles are indeed not detectable in the possible precursors of human Langerhans cells and tend to disappear in cultured human Langerhans cells. The mechanisms that lead to the appearance of Birbeck granules in epidermal Langerhans cells and to their later disappearance still remain unknown. In the present study we show that the more or less dilated elements of the surface-connected canalicular system of human blood platelets collapse after EDTA treatment. Made up of two parallel limiting membrane and central irregular striated density, these elements show great ultrastructural similarities with the Birbeck granules of human epidermal Langerhans cells. These platelet morphologic changes i) are directly dependent on the EDTA-induced dissociation of the glycoprotein GP IIb-IIIa, the platelet-specific calcium dependent heterodimer complex, member of the beta 3 integrin subfamily (alpha IIb beta 3) and ii) apparently result from a cross-linking of the dissociated glycoproteins. These findings lead us to propose that in the same manner cells of the Langerhans lineage, on reaching the epidermis, will find themselves in contact with an epidermal specific ligand. Interactions between this epidermal ligand and Langerhans cell receptors could then induce, all along the circuit taken by the ligand-receptor complexes, morphologic modifications, i.e., appearance of structures of Birbeck granule type. PMID- 1919042 TI - Specific nucleotide sequence of HLA-C is strongly associated with psoriasis vulgaris. PMID- 1919044 TI - Molecular analysis of HLA DP and DQ genes associated with dermatitis herpetiformis. AB - HLA class II DQ and DP genes from dermatitis herpetiformis patients were amplified and analyzed using molecular probes and compared to those from celiac disease patients and to an HLA and ethnically matched control group. In dermatitis herpetiformis, as in celiac disease, the strongest association of disease was with the DQ subregion alleles DQB1*0201 and DQA1*0501 that are linked to the DRB1*0301 allele. DQB1*0201 determines the DQw2 serologic marker whereas DRB1*0301 determines the DRw17 serologic marker (formerly termed DR3). A DP subregion allele DPB1*0301 was increased and a constellation of DPB1 alleles that included DPB1*0202, *0901, and *1301 was decreased in dermatitis herpetiformis. DPB1*0101, an allele reported to be increased in celiac disease, was not increased in dermatitis herpetiformis. DP beta chains that lack a negatively charged amino acid residue at position 69 of the DP beta chain are significantly over-represented both in dermatitis herpetiformis and celiac disease patients with the DRw17, DQw2 haplotype, compared to healthy controls with that haplotype. These data favor a multigenic model for the contribution of HLA class II D region genes to dermatitis herpetiformis susceptibility. Further, they indicate that a specific DQ molecule, when present in combination with the product of one of several different DPB1 alleles, may contribute to susceptibility to the intestinal lesion, which is common to dermatitis herpetiformis and celiac disease. PMID- 1919043 TI - Keratinocytes regulate melanocyte number in human fetal and neonatal skin equivalents. AB - To determine if keratinocytes influence melanocyte number and position in the developing epidermis we have experimentally recombined keratinocytes and melanocytes from epidermis of different stages of differentiation in the skin equivalent (SE) system. Previously we showed that developmental differences in the position and number of melanocytes characteristic of the epidermis in vivo were preserved in fetal and neonatal skin equivalents. In the present study we have combined cultured fetal or neonatal keratinocytes with age-matched or non age-matched cultured melanocytes on the dermal equivalent. The ratio of basal keratinocytes to melanocytes (BK/M) present in multiple high-power fields was determined after localization of melanocytes by staining with the melanocyte specific monoclonal antibody, HMB-45. The BK/M ratio in SE composed of neonatal keratinocytes and either fetal (n = 4) or neonatal (n = 5) melanocytes was 26.2 and 21.5, respectively. The BK/M ratio in SE composed of fetal keratinocytes and either fetal (n = 8) or neonatal (n = 5) melanocytes was 9.2 and 7.7, respectively. In each case, the BK/M ratio was dependent on the keratinocytes rather than the melanocytes. With either type of melanocyte, ratios in SE composed of neonatal keratinocytes were significantly greater than those with fetal keratinocytes. These results establish that keratinocytes regulate the BK/M ratio in this model and suggest that developmental differences between fetal and neonatal keratinocytes may be responsible for determining melanocyte numbers in the epidermal-melanin unit in vivo. The precise mechanisms that control the organization and number of melanocytes in the epidermis are unknown although keratinocytes may interact with melanocytes via growth factors, cell surface molecules, or other factors related to proliferation and differentiation of the epidermis. PMID- 1919045 TI - Differential expression of urokinase-type plasminogen activator and its type-1 inhibitor during healing of mouse skin wounds. AB - The expression of urokinase-type plasminogen activator (u-PA) and its type-1 inhibitor (PAI-1) was examined in vivo in mouse wounds by in situ hybridization and immunohistochemistry. u-PA mRNA was present in both basal and suprabasal keratinocytes in the regenerative epithelial outgrowths at the edge of the wounds. In the same area, PAI-1 mRNA was only present in the basal keratinocytes. u-PA protein was detected in keratinocytes in several layers of the epithelial outgrowth, whereas PAI-1 protein was confined to the basal keratinocytes and to the area of the basal membrane. The two proteins and their mRNA were not detected in normal epidermis or in normal-looking epidermis adjacent to the wounds. Fibroblast-like cells and fairly large stellate cells (possibly macrophages) in the granulation tissue underneath the wound contained both the two proteins and their mRNA. The large stellate cells, showing a strong hybridization signal for PAI-1 mRNA, were especially abundant at the border between the necrotic wound and the newly formed granulation tissue. The specificity of these results was supported by the use of two different non-overlapping antisense probes, sense mRNA probes, antibody preparations preabsorbed with purified proteins, and Northern analysis of tissue extracts. The localized and regulated expression of u PA and PAI-1 seen in this study may reflect that plasminogen activation plays a role in the migration of keratinocytes and connective tissue cells during reepithelialization and tissue remodeling in wound healing. PMID- 1919046 TI - Clinical, histologic, microbiologic, and biochemical characterization of the causative agent of bacillary (epithelioid) angiomatosis: a rickettsial illness with features of bartonellosis. AB - It has been suggested that bacillary (epithelioid) angiomatosis (BEA) is a manifestation of cat scratch disease (CSD). Because of clinical similarity between this condition and the verruga peruana phase of bartonellosis, we sought to further characterize this disease as well as its causative agent and to compare it to bartonellosis. We isolated a small flagellated pleomorphic bacillus from skin lesions of two patients with BEA. Organisms were stained successfully with Warthin-Starry silver stains, but immunohistochemistry failed to demonstrate binding with a polyclonal antibody directed against the cat scratch bacillus. Whole cell fatty-acid gas chromatography performed on both BEA organisms and Bartonella bacilliformis demonstrated marked similarity between the two. Electron microscopy of BEA organisms in tissue and in suspension revealed features characteristic of a gram negative bacillus. Based on these findings, we propose that this unusual rickettsial infectious disease with vascular proliferation may represent an unusual variant of infection with a bartonella-like organism rather than a manifestation of cat scratch disease. PMID- 1919047 TI - Epidermal interleukin 1 alpha functional activity and interleukin 8 immunoreactivity are increased in patients with cutaneous T-cell lymphoma. AB - Previous studies have suggested that epidermal-derived interleukin-1 is involved in the pathogenesis of cutaneous T-cell lymphoma (CTCL); however, the findings are conflicting and studies that combine immunohistochemistry and functional activity have not been performed. We investigated the interleukin-1 level in epidermis of patients with cutaneous T-cell lymphoma using both immunohistochemistry, enzyme-linked immunosorbent assays, and the thymocyte co stimulation assay. Using supernatants obtained from epidermal cell cultures, we found a significant but small increase of interleukin 1 alpha protein release from involved CTCL epidermis compared to normal epidermis from healthy individuals. Both keratinocytes and leukocytes could release interleukin-1 alpha, but the majority was derived from the keratinocytes. Interleukin-1 beta protein was not detectable. In the thymocyte assay, interleukin-1 alpha was found to be biologically active. When lymphokines derived from a T-cell clone obtained from involved CTCL skin were co-cultured with epidermal cells, an enhanced release of epidermal interleukin-1 alpha could be demonstrated. Because interleukin 1 alpha was increased, we investigated the presence of interleukin 1-inducible keratinocyte-derived interleukin 8 and found it increased in CTCL epidermis compared to normal epidermis from healthy individuals. This study demonstrated an elevated epidermal IL-1 alpha level and IL-8 immunoreactivity in CTCL epidermis, which suggests that this elevated level is induced by lymphokines released from activated T cells. PMID- 1919048 TI - Retrovirus-mediated transduction of cultured epidermal keratinocytes. AB - Retrovirus-mediated gene transfer is an efficient means of introducing and expressing exogenous gene(s) in many cell types including keratinocytes. However, parameters of transduction and gene expression have not been systematically analyzed for keratinocytes. To carry out such a study we have transduced cultures of newborn foreskin cells with retroviral vectors that encode the genes for neomycin resistance (neor) and for beta-galactosidase (B-gal). The neor gene is a dominant selectable marker and the B-gal gene encodes a histochemically detectable product. Our key findings are the following: 1) all keratinocytes that form colonies can be successfully transduced at a viral titer greater than 5 x 10(6) colony-forming units/ml; 2) transduction is effected by integration of a single copy of retroviral DNA; 3) transduced cells are not at a growth disadvantage and, in fact, single clones of transduced keratinocytes can be expanded to yield over 10(9) cells, suggesting that stem cells are transduced; 4) whereas most transduced colonies exhibit B-gal staining in a high percentage of constituent cells, some colonies had a mosaic or sectored staining pattern; 5) expression of the non-selectable B-gal gene was somewhat greater in differentiated cells of the culture as compared to nondifferentiated precursors. The ability to transduce stem cells at a high efficiency and to follow expression of transduced genes in clonal progeny will allow lineage mapping in stratified epithelial tissues. PMID- 1919049 TI - TGF beta-1 and TNF alpha expression in the epidermis of patients with epidermodysplasia verruciformis. AB - In epidermodysplasia verruciformis (EV), the infection with specific human papillomaviruses (HPV) might be under control of the local immunosurveillance mechanisms related to cytokines produced by epidermal cells. We have investigated by in situ hybridization the expression of mRNA coding for TGF beta-1 and TNF alpha in the skin of patients with EV (n = 4) as compared to the skin lesions of patients with other premalignant (actinic keratosis; n = 5) or malignant (squamous cell carcinoma; n = 4) skin lesions, and to the skin of healthy individuals (n = 5). The expression of TGF beta-1 and TNF alpha mRNA was higher in the epidermis of EV patients as compared to the control skin from healthy individuals. The increased expression of mRNA for both cytokines was confirmed by northern blot analysis of RNA isolated from the skin lesions of the patient with EV. No specific signals for TGF beta-1 and TNF alpha were detected in actinic keratosis, and in cases of squamous cell carcinomas only single neoplastic cells were positive for TGF beta-1. It is conceivable that in EV TGF beta-1 and TNF alpha can be involved in the regulation of the growth and differentiation of HPV infected keratinocytes and in the persistence of HPV-induced skin lesions. PMID- 1919050 TI - Mid-infrared laser ablation of stratum corneum enhances in vitro percutaneous transport of drugs. AB - The precise removal of stratum corneum from cadaveric swine skin by a mid infrared erbium:yttrium scandium gallium garnet laser (lambda = 2.79 microns; 250 microseconds pulse width) was assessed by electrical resistance measurements and documented by histology. The effects of stratum corneum removal by laser ablation and by adhesive tape-stripping on the in vitro penetration of 3H-hydrocortisone and 125I-gamma-interferon were determined. Excised swine skin was irradiated with laser (1 J/cm2; 31 mJ/pulse; 1 Hz; 2 mm spot diameter). For skin penetration studies, laser pulses were delivered to discrete 2-mm areas to ablate up to 12.6% of the total 3-cm2 stratum corneum diffusional area. Franz in vitro skin penetration chambers were used to measure the cumulative 48-h penetration of 3H hydrocortisone and 125I-gamma-interferon in laser-treated and tape-stripped skin. Electrical resistance measurements and histologic studies demonstrated that 10-14 laser pulses at the above energy density were required to abolish skin resistance and selectively ablate stratum corneum without damage to adjacent dermal structures. Laser ablation of 12.6% of the surface area of stratum corneum produced a 2.8 and 2.1-times increase in permeability constant (kp) for 3H hydrocortisone and 125I-gamma-interferon, respectively. These studies demonstrate that a pulsed mid-infrared laser can reliably and precisely remove the stratum corneum, facilitating penetration of large molecules such as 125I-gamma interferon that cannot penetrate intact skin. This new technique may be useful for basic and clinical investigation of skin barrier properties. PMID- 1919052 TI - Differential role of lymphocyte function-associated antigens in the activation of nickel-specific peripheral blood T lymphocytes. AB - The possible role(s) of the adhesion molecules LFA-1 alpha (CD11a), LFA-1 beta(CD18), ICAM-1 (CD54), CD2 (T11, LFA-2), and LFA-3 (CD58) in the in vitro activation of nickel-specific peripheral blood (PB) T lymphocytes was studied. For this purpose, monoclonal antibodies (MoAb) to these markers were used. Both LFA-2 and LFA-3 appeared to be consistently involved, whereas LFA-1 was inconsistently involved. In studies using antigen-presenting cells (APC) isolated from peripheral blood to present nickel, anti-LFA-1 alpha and/or LFA-1 beta MoAb partially inhibited the in vitro activation of nickel-specific T lymphocytes in nine of 42 patients allergic to nickel. In the other 33 patients variable results, ranging from a slight increase or inhibition of proliferation to no inhibition at all, was observed, in particular when different anti-LFA-1 alpha MoAb were added to the cultures. In those patients who showed no inhibition when anti-LFA-1 (alpha and beta) MoAb were added, no inhibition was also observed when a mixture of anti-LFA-1 (alpha and beta) and ICAM-1 MoAb were added to the cultures. Similar results were also obtained using epidermal APC. In control experiments the various anti-LFA-1 (alpha and beta) MoAb effectively inhibited the tetanus toxoid and Con-A induced T-lymphocyte proliferation as well as the spontaneous aggregation of the JY cell line. Anti-CD2 and anti-LFA-3 MoAb strongly inhibited the proliferative responses of nickel-specific peripheral blood T lymphocytes from all 42 patients. These results indicated that the receptor-ligand interaction between CD2 and LFA-3 is essential for in vitro activation of nickel-specific peripheral blood T lymphocytes. This activation, however, does not regularly involve LFA-1 molecules on T lymphocytes. The involvement of LFA-1 in the activation of nickel-specific T lymphocytes correlated positively with high patch test scores to nickel and the disease activity in contact dermatitis patients. PMID- 1919051 TI - Presence of human papilloma virus type 16 DNA sequences in human nonmelanoma skin cancers. AB - The presence of human papillomaviruses (HPV) has been shown to be associated with the development and progression of invasive cancers of the genital tract, skin, and head and neck. In this study we analyzed 37 human nonmelanoma skin cancers (21 squamous cell carcinomas and 16 basal cell carcinomas) for the presence of HPV sequences. The polymerase chain reaction (PCR) was employed using primers designed to amplify DNA encoding the E6-E7 region of HPV types 6b/11, 16, and 18. HPV type 6b/11 and 18 sequences were absent from the DNA of all 37 tumors examined. However, HPV type 16 sequences were detected in four of 21 squamous cell carcinomas (SCC) (19%) and three of 16 basal cell carcinomas (BCC) (19%) as indicated on agarose gel electrophoresis by the presence of a single specific DNA band of predicted length. Furthermore, HPV type 16 sequences were absent in the DNA of normal skin from these seven skin cancer patients. The presence of HPV type 16 sequences in the seven skin tumors was confirmed by dot blot hybridization of PCR-amplified material to 32P-labeled HPV type 16, but not to HPV type 6/11 or 18-specific probes. These data indicate that HPV type 16, but not 6b/11 or 18, is associated with development of some human nonmelanoma skin cancers. PMID- 1919053 TI - Measurement of mechanical forces generated by skin fibroblasts embedded in a three-dimensional collagen gel. AB - Mechanical activities developed by cells play a significant role in the embryogenesis, development, and physiopathology of pluricellular organisms. A technique is described to measure in vitro the traction force developed by cells seeded into a three-dimensional polymeric collagen lattice. It is based on the use of strain gauges generating an electrical signal upon tension that is amplified and recorded. The intensity of the signal depends on the number and type of cells, cytoskeleton integrity, concentration of collagen in the lattice support, and fetal calf serum in the culture medium. Skin fibroblasts from humans and animals produce traction forces ranging from 100 to 1000 mg per million cells. In the gel under tension, the cells are in mechanical dynamic equilibrium with their support. It is suggested that the mechanical activity of fibroblasts and the control of the tension that they operate on the lattice support participate in the structural organization of the dermis and in its physiologic tension. PMID- 1919054 TI - Ultrastructural discrimination between malignant melanomas and benign nevocytic nevi using high-resolution image and multivariate analyses. AB - Prompted by the well-known difficulties of reliable and objective histologic differentiation between initial malignant melanoma (MM) and benign nevocytic nevi (NN), ultrastructural high-resolution image and multivariate analyses were evaluated for their diagnostic efficiency. Thirty-seven different features describing morphometry (area, circumference, and shape factor), amount of heterochromatin and euchromatin, chromatin homogeneity, and presence of smaller dark chromatin aggregations were determined by a MICROVAX 3500 computer in each of 1840 intraepidermal melanocytic nuclei of 17 MM and 20 NN. A strategy for the classification of cases based on the identification of markedly atypical melanocytic cells (MACS) was developed. MACS, selected in multivariate analysis with a linear combination of the eight most important features for cell classification, were found in 39.4% of the melanoma cells, but only in 0.3% of nevocytic nevus cells. The presence of MACS allowed a clear differentiation between MM and NN. All cases of MM had more than four MACS, whereas 17 cases of nevocytic nevi were MACS negative, and in each of the remaining three cases only one MAC was present. The percentage of MACS detected within intraepidermal parts of MM by using computerized high-resolution image analysis was found to be a highly efficient diagnostic marker. The new classification strategy has the potential of saving considerable time in subsequent studies, because preselected sampling and the calculation of only a few criteria have proven sufficient for correct classification of malignant melanomas. PMID- 1919055 TI - Induction of proliferation of growth-inhibited keratinocytes and fibroblasts in monolayer culture by sodium lauryl sulfate: comparison with all-trans retinoic acid. AB - We have previously shown that all-trans retinoic acid (RA) has the capacity to stimulate proliferation of growth-inhibited human epidermal keratinocytes and growth-inhibited human dermal fibroblasts. The same treatment also stimulates extracellular matrix synthesis by fibroblasts (J Invest Dermatol 93:449; 94:717). In the present study we have examined the capacity of sodium lauryl sulfate to stimulate keratinocyte and fibroblast proliferation under the same conditions. Our data show that both cell types are stimulated to proliferate. Sodium lauryl sulfate is less potent than RA; it requires a higher molar concentration to achieve optimal stimulation and the number of responding cells at optimal concentrations is less with sodium lauryl sulfate than with RA. Further, there is a rapid onset of toxicity at concentrations of sodium lauryl sulfate that are only slightly higher than the optimal stimulatory concentration. Finally, sodium lauryl sulfate is less effective than RA in stimulating production of extracellular matrix (fibronectin, thrombospondin, and laminin) by dermal fibroblasts. Despite its ability to partially mimic RA as a stimulant of keratinocyte and fibroblast growth, sodium lauryl sulfate does not activate chloramphenicol acetyl transferase in cells co-transfected with retinoic acid receptors and a retinoic acid responsive element linked to the chloramphenicol acetyl transferase gene. PMID- 1919056 TI - Cyclooxygenase activity is increased in platelets from psoriatic patients. AB - The aim of the present study was to ascertain the relationship between in vitro hyper-aggregability and alterations in arachidonic acid metabolism in platelets from psoriatic patients. We have studied the response to several concentrations of ADP, collagen, and arachidonic acid of intact platelets from psoriatic patients and normal subjects, with and without irreversible inhibition of platelet cyclooxygenase by aspirin. Apparent kinetic constants (apparent Michaelis constant [Km] and apparent maximum velocity [Vmax]) of cyclooxygenase in platelets from both controls and psoriatic patients were also studied. The maximum percentage and slope of aggregation induced by collagen or sodium arachidonate were significantly greater (p less than 0.05) in platelets from psoriasis patients, whereas lag time was significantly shorter in the psoriasis group in response to arachidonic acid only when compared to controls. Cyclooxygenase pathway blockade inhibited the response to aggregation inducers in the following order: sodium arachidonate greater than collagen greater than ADP. When platelets were pre-treated with aspirin no significant differences were observed between controls and psoriasis patients. We also found a significant increase of the apparent Vmax value (p less than 0.05) for cyclooxygenase activity in platelets from psoriatic patients in comparison with controls. Our results indicate that platelet hyperaggregation in psoriatic patients is related to enhanced cyclooxygenase activity in their platelets. PMID- 1919057 TI - Collagen cross-linking in sun-exposed and unexposed sites of aged human skin. AB - A recently described nonreducible, acid-heat stable compound, histidinohydroxylysinonorleucine (HHL), is a collagen cross-link isolated from mature skin tissue. Its abundance is related to chronologic aging of skin. The present communication describes the quantity of HHL from aged human skin of the same individuals in sun-exposed (wrist) and unexposed (buttock) sites. Punch biopsies were obtained from these sites from nine people of age 60 or older. HHL contents (moles/mole of collagen) at these sites were for wrist 0.13 +/- 0.07 and for buttock 0.69 +/- 0.17 (mean +/- SD, p less than 0.001). In addition, it was found that acute irradiation of the cross-linked peptides with UVA (up to 250 J/cm2) and UVB (up to 1 J/cm2) had no effect on HHL structure. The same treatment significantly degraded another nonreducible, stable collagen cross-link, pyridinoline. The results suggest that chronic sunlight exposure may be associated with an impediment to normal maturation of human dermal collagen resulting in tenuous amount of HHL. Thus, the process of photoaging in dermal collagen is different from that of chronologic aging in human skin. PMID- 1919058 TI - Photoprotection and 5-MOP photochemoprotection from UVR-induced DNA damage in humans: the role of skin type. AB - Sites on previously unexposed buttock skin in 18 subjects (skin types I-V) were treated daily for 2 weeks with suberythemogenic doses of solar-simulated radiation (SSR) alone, SSR plus a UVB sunscreen, and SSR plus the same sunscreen with 5-methoxypsoralen at 30 ppm. The three sites of treatment (designated SSR, SSR/S, and SSR/S/5-MOP), and a control site that received no SSR or topical treatment, were challenged with 2MED SSR 1 week after the treatment had ceased. Biopsy samples, taken within 15 min after the challenge dose, were assessed for unscheduled DNA synthesis (UDS, interpreted as a measure of DNA damage), melanin deposition, and stratum corneum thickening. Within a given skin type, when compared with controls, the significant increase in either pigmentation or stratum corneum thickening was similar for SSR and SSR/S/5-MOP. SSR/S inhibited these endpoints. Compared with controls, UDS was significantly reduced in skin types III-V by SSR and in all skin types by SSR/S/5-MOP. SSR/S elicited no effect apart from minimal reductions in skin types IV and V. Thus, the increases in pigmentation and stratum corneum thickening seen in all skin types with SSR and SSR/S/5-MOP were accompanied by reduced UDS in all skin types with SSR/S/5-MOP but only in skin types III-V with SSR. These findings suggest that, although induced pigmentation and stratum corneum thickening may account in part for the reduction of UDS, qualitative differences in induced pigmentation may exist in skin types I-II between SSR and SSR/S/5-MOP treatments. The findings can also be interpreted to indicate that SSR/S/5-MOP treatment can afford protection against DNA damage from subsequent exposure to solar ultraviolet radiation. Risk-benefit considerations on the use of sunscreens with and without 5-MOP are discussed and the conclusion is drawn that the judicious use of 5-MOP sunscreens, particularly in skin types I-II, affords an alternative option to those seeking a suntan. PMID- 1919059 TI - Polymorphonuclear leukocyte-induced detachment of cultured epidermal carcinoma cells from the substratum. AB - In an in vitro study, intended to develop tumoricidal therapy with the use of human leukocyte, an interesting phenomenon was found. Normal human polymorphonuclear leukocytes (PMN) plated on a cell line established from malignant trichilemmal cyst (DJM-1), a kind of squamous cell carcinoma, in a serum-free media and incubated for 48 h induced the detachment of DJM-1. The detachment was more extensive as the number of PMN increased. The detachment rate was 97.0% when the number of PMN and DJM-1 in a well was in a ratio 2.4:1 and the viability of detached DJM-1 was 96.5%. Two kinds of proteinase inhibitors, especially the inhibitor of neutrophil elastase, fetal bovine serum, and monoclonal anti-laminin antibody inhibited the detachment significantly. Furthermore, when PMN were seeded in a chamber with a filter membrane bottom to prevent direct contact with DJM-1, DJM-1 detachment decreased to 14.2%. In view of these results, the following mechanism was postulated. Activated by their adhesion to DJM-1, especially between laminin receptor on PMN and laminin on DJM 1, PMN secreted proteinases, resulting in DJM-1 detachment. This phenomenon might be an expression of cytotoxicity of PMN to cancer cells, because cultured cancer cells of epithelium origin such as DJM-1 can grow only after they are firmly attached to the substratum. This phenomenon, in turn, may explain the final step in the induction of epidermal-dermal separation in subepidermal bullous diseases with PMN infiltration such as bullous pemphigoid and dermatitis herpetiformis if we could regard DJM-1 as normal keratinocyte. PMID- 1919060 TI - Does cyclosporin A directly affect human Langerhans cell function? PMID- 1919061 TI - Application of intravascular ultrasound for detection and quantitation of coronary atherosclerosis. AB - Although angiography is widely utilized to assess the extent and severity of coronary artery disease (CAD), arteriography yields only a silhouette of the vessel lumen. Coronary intravascular ultrasound supplements angiography by providing a tomographic perspective of lumen geometry and vessel wall structure. Intracoronary ultrasound can now be performed in vivo utilizing small, flexible probes capable of negotiating tortuous vessels. We have performed coronary ultrasound in more than 100 patients, including a group of normal subjects, with no serious complications. Measurements of coronary lumen dimensions by angiography and ultrasound correlated closely for normal vessels (r = 0.92) and for concentrically narrowed atherosclerotic vessels (r = 0.90). However, the correlation between angiography and ultrasound was only fair for eccentrically narrowed arteries (r = 0.79) and was poor following angioplasty (r = 0.30). Coronary artery wall motion was measured by intravascular ultrasound and demonstrated significant differences between normal arteries (18% lumen area change) and atherosclerotic vessels (11% change). Coronary ultrasound demonstrated important differences in the structure of normal and atherosclerotic vessel walls. Arteries in normal subjects exhibited a thin intimal leading-edge echo (mean 0.20 mm) and subadjacent sonolucent zone (mean 0.12 mm). Atherosclerotic vessels typically demonstrated increased thickness of both structures and often exhibited dense fibrocalcific plaques that shadowed underlying anatomy. These ultrasound abnormalities were often present at angiographically normal sites. Several limitations of coronary intravascular ultrasound were apparent, including echo 'dropout', distortions produced by non coaxial imaging, and inability to image small or severely narrowed vessels. Coronary intravascular ultrasound holds great promise for the detection and quantification of CAD in the clinical setting. PMID- 1919062 TI - Intravascular ultrasound imaging for guidance of atherectomy and other plaque removal techniques. AB - Intravascular ultrasound imaging provides a direct view of atherosclerotic disease, generating in vivo information about the depth and mechanical characteristics of plaque at any point in the vessel wall. For this reason, ultrasound has significant potential to serve as a guidance modality for catheter based techniques designed to remove or ablate plaque. Although the current generation mechanical atherectomy, laser ablation and ultrasound pulverization techniques all have some specificity for attacking plaque as opposed to normal vessel wall, it appears that in practice all of these devices will continue to carry a risk of traumatizing or even perforating arteries. In addition, it seems highly likely that aggressive 'debulking' of plaque will require some type of guidance beyond angiography - a role which ultrasound is theoretically well suited to play. The purpose of this review is to consider the theoretical and practical applications of ultrasound imaging as a guide to catheter-based plaque removal and ablation techniques. Specific uses will be discussed with respect to both directional and coaxial therapeutic devices. PMID- 1919063 TI - Intracardiac echocardiography: current developments. AB - Intracardiac echocardiography refers to the method of imaging cardiac structures from intracardiac locations with the use of ultrasound catheters. Advances in catheter-based interventional cardiologic procedures to treat cardiovascular lesions and the problems encountered during those procedures due to inadequate guidance provided by fluoroscopy have given the impetus to develop other guidance modalities. Experimental explorations with intracardiac ultrasound probes have indicated that detailed visualization of cardiac structures in real-time is possible by intracardiac ultrasound. Recent advances in catheter-based ultrasound technology make it feasible to safely pass small-sized catheters in humans into various intracardiac locations and acquire images of valvular structures and various chambers. Experience with 20 MHz ultrasound catheters indicates that high resolution images of normal and abnormal structures can be obtained if the catheter is manipulated close to the region of interest. The problem of the limited depth of field associated with 20 MHz catheters has led to the fabrication of catheters with lower frequency ultrasound elements. Experimental and clinical experience with 12.5 MHz ultrasound catheters points to the capability and potential of intracardiac echocardiography to not only display normal structures but also aid in the identification of valvular abnormalities, chamber dysfunction and pericardial effusions. In addition, aortic disorders such as acute dissection, coarctation and atherosclerotic disease could be delineated. Similarly, abnormalities involving the pulmonary arteries such as pulmonary embolism, organized thrombi, peripheral pulmonary arterial stenoses, and pulmonary hypertension-induced vascular changes could be recognized. Many modifications in the catheter design are being explored. With further work in the area of catheter technology and ultrasound image processing, intracardiac echocardiography is likely to become a clinical tool. PMID- 1919064 TI - Applications of intravascular scanning and transesophageal echocardiography in congenital heart disease: tradeoffs and the merging of technologies. AB - This chapter will review the evolving role of intravascular ultrasound imaging and transesophageal echo in the care of children, infants and adults with congenital heart disease. The technologies relevant to congenital heart disease applications differ from those involving coronary disease since the intravascular structures imaged often involve visualization of large vessels and cardiac chambers. On the other hand, the requirements for transesophageal echo in children with congenital heart disease involve intraoperative (surgical) and imaging procedures in the catheterization laboratory which are performed for monitoring interventional catheterization therapy. As such, whereas the intravascular devices needed for pediatric cases involve lower frequency and sometimes larger catheters, the requirements for transesophageal echocardiography require higher frequency and smaller esophagoscopes. Applications of intravascular imaging including sizing of congenital stenoses, dilation of coarctation and valvular stenoses, imaging of intrapulmonary thrombi and monitoring of placement of ASD 'button' devices in the heart will be reviewed. The intraoperative transesophageal uses for monitoring infant surgery include procedures for tetralogy repair, transposition repair and repair of AV septal defects and other complex congenital heart disorders. Both of these 'invasive' methods of echocardiography have an important and evolving role in the management of congenital heart disease in children and infants. PMID- 1919065 TI - Ultrasound guidance of laser atherectomy. AB - Intravascular ultrasound imaging catheters and forward firing laser atherectomy systems are both being used in the coronary vascular tree of man. When used in conjunction, ultrasound imaging may reduce the probability of perforation and dissection related to laser atherectomy. A novel system is presented which combines ultrasound imaging and laser atherectomy capabilities on the same catheter. The system incorporates a holmium YAG laser directed perpendicular to the long axis of the catheter along with a co-directional ultrasound sensor. Ultrasound images are assembled by computer using the angle of the catheter tip and its linear advance associated with each ultrasound echo signal. In vivo experimental results are presented. PMID- 1919066 TI - Imaging of post-mortem coronary arteries by 30 MHz intravascular ultrasound. AB - Intravascular ultrasound cross-sectional imaging of the atherosclerotic artery may be employed to guide plaque ablation by spark erosion, atherectomy, laser irradiation or other means. To assess whether in the coronary artery the echolucent zone of the three-layered ultrasound appearance of muscular arteries might be a reliable boundary to halt transluminal ablative angioplasty, epicardial coronary arteries were scanned under pressure over a distance of 4-8 cm at 1 mm intervals. A 5.2F catheter with a 30 MHz transducer rotating at 600 RPM was used. In 419 images from four post-mortem hearts, aged at death 22, 31, 56 and 82 years, the presence of a distinct echolucent zone was scored as percentage of the wall circumference. The median scores were 0%, 0%, 10% and 75%, respectively. In the three youngest hearts, the three-layered appearance was largely absent. In the 82 year old heart, in contrast, the three-layered appearance could generally be identified. Within subjects, the presence of an echolucent zone was variable in location. Qualitatively, neither abundant medial elastin tissue nor a reduced medial thickness could explain the absence of an echolucent zone when the ultrasound image was compared to the corresponding microscopic section. The results show that in the 82 year old heart, 30 MHz intravascular ultrasound discrimination of coronary wall layers would be adequate to guide transluminal plaque ablation. In the younger hearts, guided ablation would fail due to the limited presence of a distinct echolucent zone as an ultrasound landmark of the media. Whether the presence or absence of an echolucent zone is related to age remains to be determined. PMID- 1919067 TI - Validation of quantitative analysis of intravascular ultrasound images. AB - This study investigated the accuracy and reproducibility of a computer-aided method for quantification of intravascular ultrasound. The computer analysis system was developed on an IBM compatible PC/AT equipped with a framegrabber. The quantitative assessment of lumen area, lesion area and percent area obstruction was performed by tracing the boundaries of the free lumen and original lumen. Accuracy of the analysis system was tested in a phantom study. Echographic measurements of lumen and lesion area derived from 16 arterial specimens were compared with data obtained by histology. The differences in lesion area measurements between histology and ultrasound were minimal (mean +/- SD: -0.27 +/ 1.79 mm2, p greater than 0.05). Lumen area measurements from histology were significantly smaller than those with ultrasound due to mechanical deformation of histologic specimens (-5.38 +/- 5.09 mm2, p less than 0.05). For comparison with angiography, 18 ultrasound cross-sections were obtained in vivo from 8 healthy peripheral arteries. Luminal areas obtained by angiography were similar to those by ultrasound (-0.52 +/- 5.15 mm2, p greater than 0.05). Finally, intra- and interobserver variability of our quantitative method was evaluated in measurements of 100 in vivo ultrasound images. The results showed that variations in lumen area measurements were low (5%) whereas variations in lesion area and percent area obstruction were relatively high (13%, 10%, respectively). Results of this study indicate that our quantitative method provides accurate and reproducible measurements of lumen and lesion area. Thus, intravascular ultrasound can be used for clinical investigation, including assessment of vascular stenosis and evaluation of therapeutic intervention. PMID- 1919068 TI - Tissue characterization with intra-arterial ultrasound: special promise and problems. AB - Although we are able to identify many tissue types based on the screen image in intravascular ultrasound, there is additional information in the ultrasound signal which could be of assistance in characterization and identification of tissue. Intravascular ultrasound has several special characteristics which affect tissue characterization. These include the high transducer frequency, small transducers, short and relatively uniform path to the tissue, and limited tissue types to identify. These characteristics influence the results obtained by absolute backscatter, local statistics, frequency dependent backscatter, and angle dependency of backscatter. These effects are both positive and negative, and in many cases can be observed in clinical imaging. Another area of tissue characterization which can be performed with ultrasound is measurement of arterial wall elasticity. This can be of importance in the evaluation of mechanisms of dilatation, and the potential for complications. PMID- 1919070 TI - Possibilities of ultrasound catheters. AB - Ultrasound catheters offer the possibility of various non-imaging applications. Some of these applications, now in different stages of development, have been studied and will be described here in some detail. Ultrasonically marked catheters have different applications. The catheter has a miniature marker transducer mounted at the tip or some other place of interest. Initially, this device was used to localize the pacing lead tip in the heart. Connected to a transponder of a passive type this device can generate a visible localization mark on the echograph screen. The basically same system can be used for early detection of cracking of the pacing lead insulation. In this case the marker transducer works as a high-frequency signal generator and detects characteristic capacitance changes better than other methods. The electronic circuit for measurement is built into the pacemaker. Other non-imaging applications have also been studied. The marker transducer can be used for echo ranging of the distance between a His bundle fulguration electrode and the structure to be destroyed. Such an automatic 'proximity fuse' can help to avoid the firing of energy at too great a distance from the His bundle. Technology of implantable defibrillators yields the possibility for a double transducer arrangement, one transducer mounted at the patch and the other being the marker transducer. Using on-line distance measurement this arrangement enables early detection of abnormal movement of the ventricle wall, thus detecting deterioration of the muscle function before it is electrically evident. The measurement was simulated in vitro. Measurement of axial blood flow using transit time methods, instead of Doppler, was also experimentally studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919069 TI - Backscatter directivity and integrated backscatter power of arterial tissue. AB - A 27 MHz transducer, mounted on an ultrasonic microscope, was used to quantify the dependence of backscatter power on the angle of incidence of arterial vessels. Due to variations in the angle of incidence significant variations in backscatter power were found in the intima, the muscular and elastic media, the adventitia and the external elastic lamina. The muscular and the elastic media show anisotropic behaviour in their angle dependence, i.e. the extent of the angle dependence depends on the direction of angle variation. This anisotropic nature is probably caused by the dominant orientation of smooth muscle cells or elastin fibers in these tissue layers. Measurements on 13 specimens of the iliac artery showed that each tissue type of the vessel has its own specific angle dependent behaviour. In the future this property might be used for quantitative tissue characterization. PMID- 1919071 TI - Application of intraluminal ultrasound imaging to vascular stenting. AB - Over the past few years catheter-based intraluminal ultrasound (IVUS) has emerged as a promising and imaginative technique which can significantly extend our understanding of atherosclerotic lesions both before and following interventions. In relation to stent implantation intravascular ultrasound appears well suited as an imaging modality--providing information as to lumen shape lesion surface and topography, as well as wall composition. To this end arteriography is unable to provide such detailed information. The purpose of this review is to outline the characteristics of stents and endoluminal support devices, currently under investigation, and the role of ultravascular ultrasound in this respect. PMID- 1919072 TI - An interferon-induced 16-kD protein is present in the membranes of interferon sensitive but not in interferon-resistant mouse cells. AB - Human interferon-alpha (IFN-alpha) or IFN-beta has been shown to induce a 17-kD membrane protein in human cells which when eluted from SDS gels inhibited the multiplication of cells of different human cell lines. We show herein that mouse IFN-alpha/beta induces a 16-kD membrane protein in L1210 and Friend erythroleukemia cells sensitive to IFN-alpha/beta, (but not in the derived IFN alpha/beta-resistant cell lines) as well in primary and monolayer cultures of mouse embryonic fibroblasts and adult mouse hepatocytes, and in suspensions of spleen cells. In addition, IFN-alpha/beta enhanced the expression of an 11-kD membrane protein which could be shown by immunoprecipitation to be beta 2 microglobulin. Anticell proliferation activity was not recovered from the 16-kD fraction of the SDS gels. PMID- 1919074 TI - Induction of trophoblastic interferon expression in ovine blastocysts after treatment with double-stranded RNA. AB - Ovine trophoblast protein-1 (oTP-1) is an interferon (IFN) related to the IFN omega. The objectives of this research were: (i) to attempt to induce oTP-1 mRNA in day-11 ovine conceptuses with polyinosinic-polycytidylic acid (poly(I).poly(C], and (ii) to determine if IFN-omega mRNA is also produced on day 11 of gestation. In experiment I, conceptuses were cultured in presence of 100 micrograms/ml poly(I).poly(C) (n = 5) or medium alone (control, n = 3) for up to 8 h. In situ hybridization was used to assess effects of treatment on mRNA concentrations for oTP-1 and actin (positive hybridization control). Poly(I).poly(C) increased oTP-1 mRNA concentrations approximately 2.5-fold (p less than 0.01), but had no effect on actin mRNA. In experiment II, the presence of mRNA for oTP-1 and ovine IFN-omega was determined by using reverse transcription-polymerase chain reaction (RT-PCR) analysis of conceptus total RNA coupled with Southern blot hybridization of the PCR reaction products with specific cDNA probes. oTP-1 mRNA was detectable in all poly(I).poly(C)-treated (n = 7) and control (n = 6) conceptuses, whereas IFN-omega mRNA was detected in only three of seven poly(I).poly(C)-treated conceptuses and not in any controls. Together these results demonstrate that expression of oTP-1 mRNA can be enhanced by treatment with poly(I).poly(C) and that oTP-1 is the primary but not the only type I-IFN inducible in conceptuses on day 11 of gestation. PMID- 1919073 TI - Direct induction of interferon-gamma- and interferon-alpha/beta-inducible genes by double-stranded RNA. AB - Using Northern analysis, we here show that the inducibility by double-stranded (ds) RNA of interferon-alpha/beta-inducible genes is not restricted to a few genes but extends to all the genes known to be stimulated by IFN type I in fibroblasts. Moreover, we show that some genes, preferentially regulated by IFN gamma, are also activated by dsRNA. We present a series of arguments demonstrating that the induction by dsRNA is not mediated by IFN. In addition to the fact that this induction occurs in the presence of cycloheximide and/or anti IFN-alpha/beta antibodies in fibroblasts, we observed that, in IFN-resistant Daudi cells, ISG15 and IP-10 genes which are not induced by IFN-beta, are still inducible by dsRNA. dsRNA is also still active on 2-5 AS and ISG15 genes in cells carrying homozygous deletions of IFN alpha/beta genes. Actinomycin D experiments and nuclear in vitro elongation assays reveal that the induction by dsRNA involves, as its early step, a transcriptional event. This induction was found not to require protein synthesis, suggesting that activation of preexisting cellular factors is involved. The opposite inducibility by dsRNA of IFN-beta and 2',5'-oligoadenylate (2-5A) synthetase genes in serum-deprived fibroblasts indicates that pathways of induction by dsRNA of these two genes are not identical. Inhibition by 2-aminopurine of the induction of IFN-inducible mRNAs by IFN-beta or dsRNA suggests the participation of a protein kinase in their mechanism of action. PMID- 1919075 TI - Metabolic interaction of recombinant interferon-beta and zidovudine in AIDS patients. AB - Zidovudine (AZT), the only currently approved drug for treatment of human immunodeficiency virus (HIV) in AIDS, is known to be metabolized by mammalian systems to a variety of metabolites including 3'-azido-3'-deoxy-5'-O-glucuronide (GAZT). Interferons (IFNs) are known to alter the microsomal enzyme system responsible for the metabolism of some compounds. The aim of the present study was to investigate the effect of combination therapy of recombinant (r) IFN-beta and AZT on the rates of metabolism of AZT in AIDS patients. AZT was given orally (200 mg every 4 h) for 8 weeks prior to initiation of rIFN-beta therapy (45 X 10(6) U/day, s.c.). Serum samples from 8 patients were obtained prior to and at days 3 and 15 following initiation of rIFN-beta therapy. Serum was analyzed by high-performance liquid chromatography (HPLC) for both AZT and GAZT. The serum data were analyzed by a computer-assisted pharmacokinetics program that calculates rates of AZT metabolism. The half life for AZT was increased approximately two-fold by day 15. The rate of metabolism of AZT was diminished from 1.43 h-1 prior to IFN-beta therapy, to 0.4 h-1 and 0.05 h-1 at days 3 and 15, respectively. The volume of distribution of AZT was 2 l/kg at day 0 and increased to 3.2 and 3.5 l/kg on days 3 and 15, respectively. In conclusion, the results indicate that rIFN-beta inhibits the rate of AZT metabolism in AIDS patients. PMID- 1919077 TI - The antiviral potentials of Mx proteins. PMID- 1919076 TI - Immunotherapy of murine visceral leishmaniasis with murine recombinant interferon gamma and MTP-PE encapsulated in liposomes. AB - The efficiency of immunotherapy with murine recombinant interferon-gamma (rIFN gamma) in mouse visceral leishmaniasis caused by Leishmania donovani was examined. To avoid the side effects encountered after the in vivo administration of high dosages of free IFN-gamma, this lymphokine and muramyltripeptide (MTP-PE) were encapsulated into multilamellar liposomes. We established that a combination of 5 X 10(3) U of IFN-gamma and 6 micrograms of MTP-PE, encapsulated in liposomes and given i.v. in C56BL/6 and BALB/c mice activates macrophages from spleen and liver in vivo to kill L. donovani in vitro. Neither empty liposomes nor the same concentration of free IFN-gamma and/or MTP-PE injected i.v. resulted in a leishmanicidal activity of these macrophage populations. For verification of these results in an in vivo infection model, susceptible mice were infected with L. donovani and were treated with IFN-gamma and MTP-PE encapsulated in multilamellar vesicles. Treatment consisted of multiple i.v. injections beginning 4 and 2 days before infection (prophylactic), either simultaneously with the infection or at various times of the exacerbation and remission phases of visceral leishmaniasis. These mouse strains treated with IFN-gamma and MTP-PE in liposomes had significantly fewer splenic parasites than untreated mice or control animals treated with free drugs or empty liposomes. The targetting of multilamellar vesicles to liver and spleen make them particularly suited for the delivery of macrophage-activating substances used for treatment of visceral L. donovani infection. PMID- 1919078 TI - Rapid production of interferon-gamma in uninduced human leukocyte suspensions. AB - Human leukocytes produced interferon-gamma (IFN-gamma) rapidly without induction during incubation at 37 degrees C. The intracellular level peaked at 3 h; the extracellular IFN-gamma reached its maximum at 7 h. Leukocytes purified by different methods, and whether from single donors or pooled from numerous donors, yielded similar amounts of IFN. The best yields were approximately 3 IU/10(6) cells. The highest titers were obtained at cell concentrations ranging between 30 and 100 X 10(6)/ml, and at these concentrations, the production of IFN-gamma was not affected by the presence or absence of serum. At lower cell concentrations, the yield of IFN per cell decreased markedly in the absence of serum. The cultural conditions and medium were not very critical; leukocytes incubated in various suspension and stationary cultures consistently produced IFN-gamma. We did not identify the mechanism responsible for the rapid production of IFN-gamma in vitro, but found no evidence of a role of calcium. Immunoaffinity-purified IFN gamma from uninduced leukocytes and from leukocytes induced with lentil lectin behaved differently in gel filtration. PMID- 1919079 TI - Cold abscesses and scrofuloderma in a patient of lepromatous leprosy. PMID- 1919081 TI - Inter observer agreement in clinical diagnosis. PMID- 1919080 TI - Dapsone induced methaemoglobinaemia. PMID- 1919082 TI - Profile of blood elements in leprosy patients. AB - Blood levels of 40 elements in 14 leprosy patients and 5 control subjects living near Mukinge Hospital in the North Western Province of Zambia were determined by spectrophotometry. In patients, compared to controls, serum levels of titanium, silicon, potassium and platinum were significantly higher; red cell levels of phosphorus were lower but those of antimony, bismuth, nickel, titanium, yttrium, silicon and platinum were higher; and whole blood levels of phosphorus, selenium, antimony and silver were lower. There were also significant differences in levels of certain elements when histologically active and inactive patients were compared and between the polar forms of leprosy. The data are consistent with a hypothesis of metabolic and nutritional involvement in the etiology of leprosy. PMID- 1919083 TI - Workshop on multidrug therapy of leprosy in low-endemic areas: an evaluation. PMID- 1919084 TI - Conference of voluntary leprosy institutions of Maharashtra, Panvel 13th & 15th December, 1990. PMID- 1919085 TI - Southern regional I.A.L. conference on multidrug therapy, Tirupathi, 21 & 22 Jan. 1991. PMID- 1919086 TI - 1990 Padma Shri Award. PMID- 1919087 TI - 8th annual Fr. Maschio Humanitarian Award. PMID- 1919088 TI - Relapse rate in paucibacillary leprosy patients after multidrug therapy in North Arcot District. AB - Surveillance data from 14,227 paucibacillary (PB) patients who had been released from treatment one year earlier, after completing multidrug therapy (PB regimen) for 6 to 12 months, were analysed to assess relapse rates and the influence of three variables, viz., number of lesions, nerve involvement and duration of treatment. The overall relapse rate at one year of surveillance was acceptably low at 0.34%. Relapse rates were about four times higher when there were many (4 9) lesions, or, when nerve was involved (0.80% cf 0.20%). Extending the duration of treatment beyond 6 months did not reduce the relapse rates significantly in the high risk groups. Detection of PB cases early, before these risk factors become operative, and treating them with MDT would appear to be the best strategy to minimize relapse rates. PMID- 1919090 TI - Epidemiological significance of indeterminate leprosy--a hospital based study. AB - An epidemiological analysis of 100 cases of indeterminate leprosy attending the Department of Dermatology and Venereology of Medical College Hospital, Trivandrum, is presented. It was found that indeterminate leprosy formed 13.23% of all cases of leprosy and 1.3% of all out-patients attending this department. Only 27% of patients with indeterminate leprosy were below 15 years of age. There was a predominance of males especially over 20 years of age. There was no history of contact with leprosy in any of the patients with indeterminate leprosy. All patients with indeterminate leprosy came for hypopigmented patches, suspecting leprosy. Majority had the disease for more than 6 months. Single lesion on the outer aspect of extremity was the most common presentation. The lepromin test was positive in only 2% of patients with indeterminate leprosy, while it was positive in 80% of control subjects. Three cases of dapsone resistance were suspected in this series. The epidemiological significance of the findings is discussed. PMID- 1919089 TI - Mouse footpad pathogenicity of leprosy derived nocardioform bacteria cultivated in vitro. AB - In vitro cultures of the nocardioform bacteria from leprosy-infected tissues consisted of granules and bacilli. Inoculation of these granules into mouse footpads (MFP) produced a mild, localised, inflammation for 4-6 weeks. The granules evoked typical granulomatous response in the subcutaneous tissue and showed gradual disintegration. Infiltration of muscles, connective tissue and epithelial cells by bacillary/mycelial masses was seen very frequently, and that of nerve bundles occasionally. Plenty of mycelial tufts emanated from many 'macrophage globi'. By 6-8 months, the granules disintegrated nearly completely releasing a large number of acid-fast bacilli (AFB), single layered rings of AFB, small globi and some residual mycelia. These AFB, harvested from the MFP, were similar to or indistinguishable from the bacillary preparations from the in vitro cultures and from the leprosy bacillus obtained directly from humans or as passaged into the MFP, on the basis of many criteria studied, including the 36k gene positivity. PMID- 1919091 TI - Relapse in leprosy after multidrug therapy and its differential diagnosis with reversal reaction. AB - Relapse may be caused either by persisters or through reinfection in a patient released from treatment after MDT. Differentiating relapse from reversal reaction is not always easy, on histological and clinical grounds. A therapeutic trial with steroids for 2-4 weeks can be used to differentiate relapse from reversal reaction occurring in the skins. However, if a patient develops nerve function deficit after release from treatment, it is best to initiate antileprosy treatment along with a long course of steroids. PMID- 1919093 TI - Clofazimine--a review. PMID- 1919092 TI - A computerized information system for evaluation of NLEP through monthly progress reports. AB - A computerized system for monitoring district-wise operational performance and epidemiological progress using existing regular and special monthly reports of the National Leprosy Eradication Programme (NLEP) is presented. The same system, with some minor modifications could be used for programme assessment at the Leprosy Control Unit level also. The advantage of the system is the speed with which it can generate output in the form of comparative tables and graphs for different regions for use by programme managers for making overall assessments in time and for sending feedback reports to workers at various levels, for self assessment and for taking timely corrective action. The system presented provides immediate and easy access to the stored and/or processed information (indicators etc.,) at any time. The system has been pilot-tested using monthly reports from eighteen districts of Tamil Nadu. PMID- 1919094 TI - Training of health posts personnel in urban leprosy programme--a preliminary report. PMID- 1919095 TI - [Studies on the enteropathogenic mechanism of non-O1 Vibrio cholerae. II. Lethality, adhesion, colonization and cytopathogenicity of enteropathogenic strains]. AB - Lethality, adhesion, colonization, hemagglutinable activity, invasiveness and cytopathogenicity of non-O1 V. cholerae were compared between enteropathogenic and non-enteropathogenic strains. The following results were obtained. 1) Minimum lethal doses (MLD) of enteropathogenic strains were significantly lower than those of non-enteropathogenic strains. 2) There were no differences in adhesive and hemagglutinating activities between enteropathogenic and non-enteropathogenic strains. 3) A greater majority of enteropathogenic strains showed cytopathogenic effect on HEp 2 cells, but non-enteropathogenic strains did not. 4) Regardless of enteropathogenicity of viable cells, none of the 13 strains examined were found to be invasive to HEp 2 cells. These results suggest that adhesion and colonization do not draw a clear distinction between enteropathogenic and non enteropathogenic strains, and that both lethal and cytopathogenic activities of these organisms are correlated with enteropathogenicity. PMID- 1919096 TI - [Elastase activity in bronchoalveolar lavage fluid from patients with diffuse panbronchiolitis]. AB - The clinical and pathological features of diffuse panbronchiolitis (DPB) have been well reported to date though its pathogenesis remains unknown. This study was designed to evaluate the protease antiprotease imbalance in patients with DPB. For this purpose, we performed bronchoalveolar lavage (BAL) in sixteen patients with DPB, twelve patients with chronic bronchitis (CB) and control subjects (nine smokers and eleven non-smokers), and determined elastase activity and alpha 1 antitrypsin (alpha 1 AT) concentration in bronchoalveolar lavage fluid (BALF). Elastase activity was measured using a synthetic substrate, succinyl-tri-L-alanine-p-nitroanilide. BALF from eleven of sixteen patients with DPB showed elastase activity. However, only two of twelve patients with CB showed elastase activity, and control subjects did not show any elastase activity in BALF. Although alpha 1 AT concentration is elevated in BALF from patients with DPB, it is assumed that elastase burden exceeded the elastase inhibitory capacity of alpha 1 AT in BALF. The percentage of neutrophils in BALF correlated significantly with elastase activity which was inhibited by DFP, but not by EDTA. These data revealed that the elastase in BALF was a serine protease of neutrophil origin. In five DPB-patients treated with low-dose long-term erythromycin chemotherapy, elastase activity in BALF decreased significantly. The above mentioned findings suggest that the neutrophil elastase plays an important role in the pathogenesis of DPB, and the mode of action of erythromycin on DPB is to decrease the elastase burden. PMID- 1919098 TI - [Evaluation of beta-glucuronidase activity for the isolation of diarrhea-causing Escherichia coli]. AB - To compare the isolating efficiency of diarrhea-causing Escherichia coli between Fluorocult agar plates, which reveal the beta-glucuronidase activity of E. coli, and a combination of SS and DHL agar plates, a total of 330 fecal specimens collected from outpatients were examined. Diarrhea-causing E. coli, identified by serological and toxigenic characters, were demonstrated in 52 samples. Among these specimens, 35 samples tested were positive on the Fluorocult agar plates, and 26 samples on the combination of SS and DHL agar plates. However, only 10 samples were positive on both the Fluorocult agar plates and the combination of SS and DHL agar plates. Thus, using Fluorocult agar plates for the isolation of diarrhea-causing E. coli in addition to the conventional SS and DHL agar plates will improve isolating efficacy. PMID- 1919097 TI - [Comparison of efficacy of powder and tablet of mebendazole in the treatment of strongyloidiasis]. AB - We previously treated 47 patients with 100 mg of mebendazole (MBZ) twice a day by oral use for 5 days and this treatment was repeated 1, 3 and 4 weeks later. Although the cure rate was 100%, liver injury was observed in 48.9% of the patients. On this study, we reduced the periods of administration of MBZ (powder; 100 mg twice a day) to 4 days, and repeated it once after 3 days interval, and this initial treatment was performed one more time after 10 days interval (group 1). As Strongyloides stercoralis is mainly located in upper digestive systems, we used the drug reduced to powder for the purpose of better contact with the parasites. We considered that the powder should be absorbed well and liver injury occurred in high incidence. As group 2, we used the tablet itself in the same schedules of group 1. The results obtained were as follows; 1) The eradication rates at 10 days after the initial treatment were 97.8% (44 of 45 patients) in group 1 (powder) and 93.0% (40/43) in group 2 (tablet). 2) At 3 days after the whole treatment, the eradication rates were 100.0% in group 1, and 97.7% (42/43) in group 2. 3) Slight side effects such as constipation (6.7% in the group 1), dizziness or vertigo (6.7% in the group 1) and itching (6.7% in the group 2) were observed. 4) Liver injury was observed at 11.1% (5/45) 10 days after the initial treatment in the group 1 and 13.3% (6/45) in the group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919099 TI - [A study of bronchoalveolar lavage analysis in patients with diffuse panbronchiolitis--the results of low dose and long term erythromycin treatment]. AB - Cellular analysis including lymphocyte surface markers in BALF in 17 patients with DPB (14 male; 36 female) was performed. The total number of cells increased remarkably, especially the percentage of neutrophils (72.9 +/- 14.1%). On the contrary the percentage of alveolar macrophage decreased (15.4 +/- 8.9%). The CD4/CD8 ratio in DPB was also significantly decreased to 0.73 +/- 0.38% when compared with normal healthy nonsmokers. Five patients with low dose and long term EM treatment were analyzed. Total cell counts as well as the neutrophil percentage (7.3 +/- 4.0%) decreased significantly. On the other hand the percentage of alveolar macrophage increased to 76.6 +/- 0.6%, which was almost similar to those obtained from normal healthy volunteers. Therefore it is concluded that both clinical and BALF findings improved concordantly after EM treatment. PMID- 1919100 TI - Bacteremia from transurethral prostatic resection under prophylactic use of antibiotics. AB - We studied the incidence of the postoperative bacteremia developing in 44 patients undergoing transurethral resection of the prostate under prophylactic use of antibiotics. In 15 of the patients, postoperative endotoxinemia was also investigated. Postoperative bacteremia was found in 10 (22.7%) of the patients, in only one of whom septicemia developed. The incidence of bacteremia was not influenced by the kind of antimicrobial agent administered prophylactically, but was significantly higher in the patients with preoperative urinary tract infection or prostatitis on histological examination of resected prostatic tissue (p less than 0.01). Concerning species isolated from the blood, gram-positive cocci were isolated more frequently than gram-negative bacteria, and Staphylococcus epidermidis was the most common species. In 7 (70%) of the bacteremia patients an identical species was isolated from preoperative urine cultures. In the patients with bacteremia, significant increases in white blood cell count and maximal body temperature were found within 3 hours after the procedure as compared to before the procedure. To lower the postoperative bacteremic rate, appropriate and adequate antimicrobial agents must be used preoperatively in patients with infection of the genitourinary tract. As to blood endotoxin, the endotoxin levels in the patients with postoperative fever did not significantly differ from those of the patients without this complication. PMID- 1919101 TI - [Usefulness of the mailed specimens for mass examination of Chlamydia trachomatis and Neisseria gonorrhoeae with EIA]. AB - The infections with C. trachomatis and N. gonorrhoeae have recently been determined routinely with the commercial kits for detecting the antigens of these organisms in both the clinical and mass examination laboratories. In mass examination, a change during transporting the specimens must be avoided. Hence, a study on whether the antigens were changed with atmospheric temperature was carried out. As for C. trachomatis, no change in antigen was found on the enzyme immunoassay (EIA) absorbance of the antigen quantity corresponding to the cell of 4.8 x 10(4), 2.4 x 10(4) and 6.0 x 10(3) (IFU/ml) until 5 days at 4, 25 and 37 degrees C respectively after sampling. The coefficient variation was found out to be ca. 10%. In a test on antigen stability of N. gonorrhoeae, similar results to that of C. trachomatis were obtained on the following antigen quantity: 2.4 x 10(3), 3.3 x 10(2) and 9.0 x 10 (CFU/ml) under the same conditions as in the above. The coefficient variation was found out to be 10% or less. To investigate whether there is any difference on the stability of C. trachomatis antigen between mailing and hand carrying, a total of 133 specimens collected from many clinics were subjected to the detection of antigen with the commercial EIA kits. The results of comparison on both transport methods were as follows: agreement rate 96.2%, positive rate 100% and negative rate 95.2%. The highly correlation between the both transportation was confirmed in the detection of antigen; that is, Y = 1.03X + 0.03, r = 0.936.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919102 TI - [Clinical research on patients with typhoid and paratyphoid fever (1984-1987). Research Group for Infectious Enteric Diseases, Japan]. AB - Patients with typhoid or paratyphoid fever, admitted to 14 hospitals for infectious diseases during 1984-1987, were epidemically and clinically studied. Of the total number of 183 typhoid, 49 paratyphoid fever patients, those infected overseas was 44.3% and 71.4% respectively, giving an overall annual decrease, yet marking an increased ratio of overseas infection. Patients aged 20s-30s and males were dominant. One hundred and seventy six cases (96.2%) of typhoid and all the paratyphoid fever cases were bacteriologically diagnosed. The period from the onset to the diagnosis was around 14 days in most cases, but beyond 29 days in over 10% of the cases. We would like to emphasize that enteric fever, focusing on high fever, bradycardia, roseola, hepatosplenomegaly, leukopenia, elevated serum GOT GPT and LDH, can be easily diagnosed by blood/stool culture before beginning chemotherapy. Intestinal bleeding was recognized in 24 cases (13.1%) of typhoid and 4 (8.2%) of paratyphoid fever, intestinal perforation in 2 (1.1%) and death in 1 (0.5%) of typhoid fever. CP was most commonly used in chemotherapy. Bacteriological relapse was recognized in 7/127 cases (5.5%) of typhoid, 6/48 (13.0%) of paratyphoid fever those followed beyond 3 weeks, though eradication was attained by retreatment. One strain of S. typhi resistant to CP.ABPC.KM.SM was isolated in 1986 from a patient infected overseas. New quinolones seem reliable in our preliminary studies. PMID- 1919103 TI - [Epidemic of echovirus type 7 in Kitakyushu City in 1986--a survey of isolation of viruses from the sewage and seroepidemiology of children]. AB - In 1986, under the Infectious Disease Surveillance system in Fukuoka Prefecture, no isolation of echovirus type 7 from aseptic meningitis patients were reported. It was unclear that epidemics of this virus occurred in Fukuoka Prefecture, including Kitakyushu City. We tried to isolate enteric viruses from the sewage (activated sludges) in Kitakyushu City in 1986. Outbreaks of isolations of echovirus type 7 started in September and continued until in December. This result suggested that echovirus type 7 caused epidemic during this period in Kitakyushu City. Sera were collected from children in 1989, and were examined neutralizing antibody titer against echovirus type 7. Antibody titers were positive in the sera of about half of children above 1 year of age in 1986. From results of virus isolations from the sewage and serological study, it was confirmed that echovirus type 7, reported no isolation in Fukuoka Prefectural surveillance system, caused epidemics in Kitakyushu City in 1986. PMID- 1919104 TI - [A clinical study on liver dysfunction in patients with acute measles infection]. AB - Liver dysfunction in patients with measles infection is reported commonly in European and American literatures, but those in Japan are relatively rare. We observed the abnormal elevation of serum transaminase in 17 of 18 juvenile patients with measles from December 1989 to February 1990, however severe complications such as pneumonia or meningitis were not observed. A diagnosis of measles was made by typical clinical symptoms and the elevation of IgM antibody against measles (EIA method). Ninety four percent of the patients showed the elevation of serum transaminase, (GOT 118.6 +/- 96.2 IU/l, GPT 161.5 +/- 167.6 IU/l), and all patients recovered completely in 30.5 +/- 12.8 days after the onset. The abnormal evaluation of serum LDH was seen in 94% of the patients, (mean value was 872.2 +/- 216.2 IU/l). LDH4 mainly elevated in most cases, however, LDH5 elevated only in 4 cases. The intensity of liver dysfunction did not correlate to the severity of measles in the present cases. It is considered to be characteristic to the patients with measles that the serum level of LDH is markedly high as compared with that of transaminase. PMID- 1919106 TI - [A case of tsutsugamushi disease in the urban area of Komatsu City]. AB - Most of patients with tsutsugamushi disease are diagnosed by their clinical histories suggesting the opportunities of Rickettsia infection in a rural region. We reported a 76-year-old female patient, who was considered to be infected in her house in the urban area of Komatsu City. She has shown typical clinical manifestations of tsutsugamushi disease, and was remitted successfully by oral administration of minocycline. Although specific antibodies to Rickettsia tsutsugamushi could not be detected in her serum by the complement fixation (CF) method during her clinical course, their significant elevation was confirmed by the indirect immunofluorescence (IF) method. PMID- 1919105 TI - [A case of Enterococcus faecalis brain abscess in a patient with suprapharyngeal cancer]. AB - A 55-year-old male was admitted to our hospital for the treatment of suspected brain abscess on March 18, 1989. The brain CT scan showed low density area with ring enhancement. After admission, both cefminox 2 g/day and clindamycin 500 mg/day were administered intravenously. On March 29, 1989, the patient developed cerebral herniation suddenly. Therefore emergency burr hole operation was done. Many gram-positive cocci were observed on gram-staining of the aspirated pus. Moreover neutrophils with phagocytosed gram-positive cocci were also observed. Culture of aspirated pus revealed colonies of gram-positive cocci which were subsequently identified as E. faecalis. Same species of bacteria were also isolated from fistula of right mastoid. From both findings of brain CT scan and data of MICs of E. faecalis, it may be suggested that direct infection developed from right mastoiditis to intracranial space. We experienced a severe case who developed cerebral herniation because of brain abscess due to E. faecalis which is an infrequent pathogen of brain abscess. PMID- 1919107 TI - [Three cases of psittacosis]. AB - Case 1 was a 55 year old female whose primary complaint was pyrexia. Anamnesis consisted of a fever at a 39 degrees C level beginning on September 15, 1987 with headache and muscle pain. The patient was examined by a nearby physician. Despite taking medication, there was no break in the fever. The patient was examined and admitted to this institution on September 18. Case 2 was a 32 year old female whose primary complaint was pyrexia and an abnormal sensation in the pharynx. Anamnesis consisted of a fever at a 39 degrees C level beginning on February 13, 1989 and the manifestation of a cough beginning on February 17. Although the fever broke on February 20, as the abnormal sensation in the pharynx persisted, the patient was examined and admitted to this institution on February 21. Case 3 was a 42 year old male whose primary complaint was pyrexia. Anamnesis consisted of a fever of 38 degrees C, cough and a sensation of pressure in the right precordia beginning on November 18, 1989. The patient was examined and admitted to this institution on November 21. Chest X-rays revealed the presence of atypical pneumonia in all three cases. As a significant rise in antibodies to the Chlamydia of parrot fever was observed in the cases at the time of admittance as well as after admittance, treatment was begun by administration of Minocycline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919108 TI - [Detection of influenza virus with PCR (polymerase chain reaction)]. PMID- 1919109 TI - [Studies on the enteropathogenic mechanism of non-O1 Vibrio cholerae. III. Production of enteroreactive toxins]. AB - Cholera toxin gene and production of enteroreactive toxins were examined in 134 strains of non-O1 V. cholerae. Results obtained were summarized as follows. Frequencies of cholera-toxin-gene-positive strains were 2/58 (3.4%) from human sources and 2/76 (2.6%) from fish and environment. While, frequencies of production of hemolysin, fluid accumulating factor (FAF) related with protease, fluid accumulating factor in the suckling mouse, NAG-rTDH, NAG-ST and Vero toxin were 100, 72, 31, 2, 0 and 0%, respectively, for 58 strains from human sources, and 100, 57, 24, 0, 1.3 and 0%, respectively, for 76 strains from fish and environment. Among the 31 strains used for the injection of viable cells to the ligated rabbit ileal loop, detection frequencies of these enteroreactive toxins in the accumulated fluids were 100% for hemolysin, 3.2% for both FAF and NAG-rTDH and 0% for cholera toxin, Vero toxin or NAG-ST. Hemolysin and the fluid accumulating factor in the suckling mouse seemed to be identical in most strains. These results suggest that cholera toxin, NAG-ST, NAG-rTDH and Vero toxin may not be very important in the enteropathogenic mechanism of a great majority of non-O1 V. cholerae strains, whereas hemolysin may play an important role in the enteropathogenicity. PMID- 1919110 TI - [Cholera toxin producibility by Vibrio cholerae isolated during the cholera outbreak in the NTT Nagoya Hall]. AB - An outbreak of cholera occurred among guests of the NTT Nagoya Hall in September 1989. Clinical findings showed that all but one were symptomatic infections out of 44 bacteriologically confirmed cases. In relation to the high incidence of symptomatic infections, we examined cholera toxin (CT) producibility of the isolated V. cholerae. 1. Strains of the NTT case produced 16-256 (mean 130) ng of CT per ml in CAYE-L medium at 30 degrees C and 32-256 (mean 142) ng of CT per ml by Polymyxin B treatment. But strains of past case produced 8-256 (mean 34), 8 128 (mean 44) ng of CT per ml, respectively. Strains of the NTT case produced a larger amount of CT than that of the past cases. 2. Strains of the NTT case produced 512-4096 (mean 2100) ng of CT per ml in CAYE-L medium at 37 degrees C and 1024-2048 (mean 1600) ng of CT per ml by Polymyxin B treatment. But strains of the past case produced 8-64 (mean 25), 8-128 (mean 45) ng of CT per ml, respectively. Strains of the NTT case produced a larger an amount of CT than them of past case. We observed the same phenomenon in AKI medium at 37 degrees C. The yield of CT in CAYE-L medium was greater at 37 degrees C than 30 degrees C. 3. Strains of NTT case grew faster than that of the past case in CAYE-L medium at 37 degrees C. But the growth rate was the same as both strains in AKI and CAYE media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919111 TI - [Hepatosplenic candidiasis in acute non-lymphocytic leukemia]. AB - Eleven patients with acute non-lymphocytic leukemia developed hepatosplenic candidiasis following the termination of chemotherapy. Five who did not receive amphoteicin B (AMPH) died of liver failure, whereas the other six who received AMPH and/or miconazole or fluconazole were cured. The features of hepatosplenic candidiasis included prolonged high fever not responsive to antibiotics and hepatomegaly with right-sided hypochondrial pain developing after severe neutropenia. Even if the neutropenia recovered, these symptoms did not subside. In addition, elevation of the serum alkaline phosphatase and total bilirubin levels were observed at onset. CT scan revealed multiple low-density areas of varying size that showed no contrast enhancement. Ultrasonography also demonstrated hypoechoic or hyperechoic lesions, and a so-called "target sign appearance" in the liver and spleen. The clinical diagnosis for hepatosplenic candidiasis is not so difficult because of the uniform symptoms, signs and laboratory abnormalities. The importance of the early administration of antifungal agents to obtain a cure is discussed in this article. PMID- 1919112 TI - [Studies on motile-Aeromonas infection: 2). Development of a bacteriophage typing system for motile Aeromonas]. AB - We succeeded in isolating Aeromonas-susceptible phages from river water and mud after a few years (1983-1985) of painstaking effort. For the first time in Japan, we investigated phagetypes of the bacterial strains isolated. The results obtained are summarized as follows: 1) Aeromonas-susceptible phages were isolated from 82 (40.1%) of 195 samples of river water and from 23 (25.6%) of 90 samples of river mud. By the cross-matching test of the phages isolated from the 105 samples, these were classified into 13 type groups (Groups I-XIII). 2) When 594 Aeromonas strains isolated from river water, lake water, river mud and fresh water fish were examined using the phage group patterns developed by us, 129 (21.7%) strains classified into these phagetypes. Phagetyping was possible for 11 (15.5%) of the 71 strains isolated from river and lake water, for 29 (35.4%) of the 82 strains from river mud and for 89 (20.2%) of the 441 strains from fresh water fish. By bacterial species, phagetyping was possible for 53 (51.5%) of the 103 strains of A. hydrophila. 21 (7.2%) of the 292 strains of A. sobria, 13 (8.8%) of the 148 strains of A. caviae and 42 (82.4%) of the 51 strains of Aeromonas spp.. Especially the phages classified as Groups I, IV and VI amounted to the majority. Thus we succeeded in isolating Aeromonas-susceptible phages which could be classified into Groups I-XIII. The results suggested the possibility of utilizing this phagetyping for analysis of the ecological distribution of genus Aeromonas. PMID- 1919113 TI - [A 23-year longitudinal study on the antibiotic sensitivities of group A streptococci from the scarlet fever patients--1956-1978]. AB - Among the group A streptococci isolated during the period 1956 to 1978 from the pharynx and the nostril of the scarlet fever patients quarantined in the Tokyo Metropolitan Toshima Hospital within 1 week of hospitalization, 1,586 strains of types 4, 6 and 12, the most prevalent serotypes, were estimated for their sensitivities to various antibiotics. Among the sensitivities, those to tetracycline (TC), chloramphenicol (CP) and erythromycin (EM), these being in close relation to prevalent serotypes, are to be reported. The first appearance of TC-resistant strain was seen in one strain (type 6) isolated in 1959, and, in 1964, the resistant strain increased in proportion in accordance with the prevalence of type 4. The resistant strain decreased a little in 1968 and in 1969, increased again from 1970, exceeded over 90% from 1973, and reached 100% in 1978. The first appearance of CP-resistant strain was seen in one strain (type 4) isolated in 1969, and then the resistant strain increased year by year along with the prevalence of type 12. The first appearance of EM-resistant strain was seen in 30 strains (type 12) isolated in 1972, and then, similarly to the case of CP resistance, the resistant strain increased year by year together with the prevalence of type 12. Meanwhile, among the 1,586 strains isolated at the time of hospitalization and estimated of their minimum inhibitory concentrations (MIC), 932 strains (58.8%), 452 strains (28.5%), and 574 strains (36.2%) showed resistance to TC, CP, and EM, respectively. Variations of drug-resistance by serotypes were as follows: TC-resistant strains increased in accordance with the prevalence of type 4 in 1964; CP- and EM-resistant strains increased in accordance with the prevalence of type 12 in 1972; and type 6 strains were low in the rate of resistant strain to any of the three drugs. So far, prevalence of a serotype of group A streptococci has been considered to be caused by the accumulation of the subjects non-immune to the serotype. In the present study, a phenomenon was observed that prevalence of a serotype was effected by the state of resistance-acquisition to commonly used drugs. It would be clear that the resistance-acquisition plays, in addition to the immune state, a great role in evoking prevalence of a serotype. PMID- 1919114 TI - [Molecular epidemiology of Vibrio cholerae O-1 from outbreak and sporadic patients in Nagoya in 1989]. AB - Enterotoxigenic strains of Vibrio cholerae O-1 biotype eltor, isolated from three sporadic cases of cholera in Nagoya in 1989 and an outbreak of cholera in Nagoya in 1989 were analyzed for their similarities. All isolates of V. cholerae O-1 were indistinguishable in bacteriophage types, serovars, biovars and drug resistance patterns. Because the epidemiological investigation based on a primary structure of chromosomal DNA is more reliable, we isolated chromosomal DNA from these isolates and compared electrophoretic patterns of restriction endonuclease digested DNA fragments. Furthermore, Southern hybridization of the cholera toxin gene was performed. Since no difference among six strains in these sporadic was observed, it was strongly suggested that both the independent cases and the outbreak of cholera were caused by the same strain. PMID- 1919115 TI - [Laboratory and clinical investigation of lysis centrifugation blood culture method for fungemia]. AB - We compared the lysis centrifugation blood culture system using Isolator (Du Pont) to the conventional blood culture bottle using BCB system (Roch), and the following results were obtained. In the investigation of experimental fungemia made by human blood and Candida albicans, the organism was detected 9/12 after 1 day and 11/12 after 3 days by Isolator, although the organism was detected 3/12 after 3 days and 11/12 after 6 days by the culture bottle system. In the experimental fungemia of Candida tropicalis, the organism was detected 12/12 after 2 days by Isolator, although it was detected 1/12 after 6 days and 4/12 after 10 days with the culture bottle system. Isolator showed faster and a more sensitive detection rate for fungemia. Clinical investigation of 94 cases (180 cultures) showed a 11.1% isolation rate with Isolator system and a 7.1% isolation rate with the culture bottle system. In 43 cases which were examined by the both systems, 7 cases were positive with Isolator, 3 positive with culture bottle. The culture bottle system isolated only Candida albicans and Candida parapsilosis, where as the Isolator isolated Candida albicans, Candida parapsilosis, Candida tropicalis, Candida krusei, and Candida spp. This investigation suggested that the Isolator system was an excellent method for the detection of fungemia. PMID- 1919116 TI - [A novel approach to the detection of Neisseria gonorrhoeae employing DNA probe method]. AB - The present study was undertaken to establish a novel detection method for Neisseria gonorrhoeae (N. gonorrhoeae). DNA probe obtained from Gen-probe Inc. was employed and clinically isolated strains (18 species, 81 strains) were applied to verify the quality and quantity of the method. The present data revealed that the method is specific to detect N. gonorrhoeae (30/30): neither gram positive nor negative oraganisms were detectable by the method (0/51). It has been shown, further more, that there exists a significant correlation between the number of the bacteria and the relative light units (r = 0.96). The threshold of cell numbers, on the other hand, was found to be 5 X 10(3) cfu/tube. The detection sensitivity for N. gonorrhoeae was not influenced by the presence of other bacteria, and not decreased by using heat-treated or drug-treated N. gonorrhoeae organisms. The present study also provides some experimental evidences that the method can also be applicable for the detection of bacteriolytic action of drugs. PMID- 1919117 TI - [Species and serovar distribution, and drug resistance of Shigella strains isolated from imported and domestic cases in 1980-1989 in Tokyo]. AB - A total of 1,189 Shigella strains consisting 804 imported and 385 domestic strains were examined for their species and serovar distribution, and their drug resistance. In both imported and domestic strains, S. sonnei was found to be the most prevalent species, followed by S. flexneri, S. boydii and S. dysenteriae in order. In imported strains, however, the isolation frequency of S. flexneri, S. boydii and S. dysenteriae were higher than that of domestic strains, and the serovar of each species was distributed in a wider range than that of the domestic strains. The drug resistance test using chloramphenicol (CP), tetracycline (TC), streptomycin (SM), kanamycin (KM), ampicillin (ABPC), sulfamethoxazole-trimethoprim (ST), nalidixic acid (NA), fosfomycin (FOM) and norfloxacin (NFLX) showed that 80.1% of the imported strains and 82.9% of the domestic strains were resistant to any of drugs examined, although frequency of resistance varied by their species. The frequency of resistance to each drugs were SM (74.0%), TC (68.5%), CP (38.8%), ABPC (35.3%), ST (34.1%), NA (1.5%) and KM (1.0%) in imported strains, and TC (79.2%), SM (55.3%), ABPC (40.3%), CP (38.4%), ST (32.4%), NA (30.5%) and KM (4.2%) in domestic strains. No strain resistant to FOM or NFLX was found in both groups. The resistance patterns varied to 32 types. Among those, a multiple drug-resistance type with CP.TC.SM.ABPC was found most frequently in both groups. Frequency of strains carrying transferable R plasmid was tested for 50 strains isolated in 1989 and three (6%) of them had the plasmid. PMID- 1919118 TI - [Formation of biofilm by slime producing Staphylococcus epidermidis and bactericidal activity of cefazolin]. AB - Slime production was studied in a total of 598 strains of Staphylococcus aureus and 11 species of coagulase negative staphylococci and the relationship of the slime production and biofilm formation was investigated. The high slime production was obtained in 42 of 263 strains (16%) of S. epidermidis only. The adherence of S. epidermidis to biomedical silicone discs (S discs) and biofilm formation were investigated in vitro in high slime producing and non-producing strains. The adherence rates of S. epidermidis to the S discs ranged from 2.3 to 14.8%. There was no relationship between slime production by S. epidermidis and the adherence rates. Biofilm was formed only in slime producing strains with cell growth on the S discs when they were incubated. The process of the biofilm formation was obtained by scanning electron microscopy; there were many projections, probably slime secreted from the cells, on the cell surface, and picture showing agglutination of cell by crosslinking. The bactericidal activity of cefazolin, cefmetazole and flumoxef against S. epidermidis after formation of the biofilm decreased more markedly than that before formation. Cefazolin reduced the number of S. epidermidis and eliminated the formed biofilm in an in vitro simulation model of serum concentration in human after drip infusion of 2 g of cefazolin. PMID- 1919119 TI - [A case report of a patient repeatedly infected with Ancylostoma duodenale, probably from himself through his artificial anus, and resistant against a single dose of pyrantel pamoate]. AB - A 88 year old Japanese male was repeatedly infected with Ancyclostoma duodenale. He underwent an artificial anus operation about 55 years ago. He appeared to be infected with hookworm earlier than in 1977 and developed severe anemia. Though he was treated with pyrantel pamoate and mebendazole several times, reinfections developed in each time. A possible origin for his reinfections was his own feces defecated through his artificial anus. Unsanitary handling of the anus and the feces exposed himself to oral or percutaneous infection. Besides, a single dose of pyrantel pamoate, usually very effective against Ancylostoma duodenale, was not so effective in this patient. Therefore, we prescribed multiple doses of pyrantel pamoate, and followed by a single dose of mebendazole. However, reinfections still persisted because of his unsanitary behavior. PMID- 1919120 TI - [A case of human-immunodeficiency virus infection related Mycobacterium tuberculosis with atypical clinical features]. AB - Increasing rates of human immunodeficiency virus (HIV) related tuberculosis have been noted and recently the clinical importance of the disease has been mentioned. The diagnosis of tuberculosis is more difficult in those patients with HIV seropositive than those with seronegative, because those with seropositive have atypical clinical features. A 29-year-old male, who was infected with HIV heterosexually in Central Africa in 1986, was admitted to our hospital with a history of general malaise and weight loss in April, 1989. Laboratory and physical examinations revealed anemia, thrombocytopenia, the elevation of LDH, and giant intraabdominal lymphadenopathies, suspecting malignant lymphoma. Mycobacterium was isolated from the sputa in April and was confirmed as M. tuberculosis using a DNA probe in May, 1989. Clinical symptoms including giant lymphadenopathies and laboratory abnormalities improved with antituberculosis therapy. Development of a rapid method for the diagnosis of tuberculosis was warranted in this case. PMID- 1919121 TI - [Alpha-hemolytic streptococcal septicemia and meningitis in immunocompromised children]. AB - Many kinds of microorganisms can produce toxic septicemia in immunocompromised hosts. We are reporting alpha-hemolytic streptococcal septicemia and meningitis in two children with hematological malignancies. [Case 1] 6 year old girl who had been suffering from acute lymphocytic leukemia. She had sepsis and bacterial meningitis in maintenance-therapy for leukemia. Streptococcus sanguis was isolated from the blood and cerebrospinal fluid (CSF). [Case 2] 11 year old girl who had had malignant lymphoma (non-Hodgkin type). She also had sepsis and bacterial meningitis due to Streptococcus mitis which was isolated from blood and CSF in maintenance-therapy. Both cases had been treated with anti-cancer drugs and had severe granulocytopenia. Positive rate of blood cultures during the recent 6 years (1984.1-1989.12) at our department was 6.0% (total number of cultures were 2,019, positive cultures were 121). Strains of 131 bacteria were determined; Gram-positive cocci were 70 strains (53.4%) and Gram-negative rods were 52 strains (39.7%). Fifteen strains (11.5%) of alpha-hemolytic Streptococci were isolated during 6 years. One hundred thirteen cases of septicemia were analysed in medical charts and 12 cases of alpha-hemolytic streptococcal septicemia were observed (5 cases with infective endocarditis and 7 cases in immunocompromised states). PMID- 1919122 TI - [Studies on the enteropathogenic mechanism of non-O1 Vibrio cholerae. IV. Role of hemolysin]. AB - The role of hemolysin in the enteropathogenic mechanism of non-O1 V. cholerae was experimentally investigated, in vitro and in vivo. Results are summarized as follows. 1). A greater majority of enteropathogenic strains produced hemolysin in Eagle MEM medium supplemented with 10% calf serum and in the rabbit ileal loop, while most non-enteropathogenic strains did not under the same conditions. 2). Non-enteropathogenic mutants derived from enteropathogenic parent strains produced much less hemolysin than that of parent strains. 3). A significant inhibition of the fluid accumulation in the ligated rabbit ileal loop test with viable cells was noted in rabbit immunized with purified hemolysin. These results indicate that hemolysin is the most important toxin in the enteropathogenic mechanism of non-O1 V. cholerae. PMID- 1919123 TI - [Isolation of vero toxin-producing Escherichia coli (enterohemorrhagic E. coli) O111:H- from 2 cases diagnosed as appendicitis]. AB - Vero toxin-producing E. coli O111:H- was isolated from 2 cases of patients with severe abdominal pain and bloody diarrhea and were diagnosed as appendicitis. E. coli from both cases produced both VT1 and VT2. PMID- 1919124 TI - [Preparation of monoclonal antibodies agglutinating group A, type 4 streptococci]. AB - BALB/C mice were immunized with a partially purified M-protein fraction prepared from hot acid-extracts of a type 4, group A streptococcus, strain SS91. Two samples of monoclonal antibodies (MAb) were obtained from hybridoma cells of antibody producing spleen cells fused with NS-1 myeloma cells. Both MAb were of the subclass IgG1 having kappa-type light chains. The MAb agglutinated trypsin digested cells of type 4 strains, but not of types 1, 2, 18, 28 and 41. This type 4-cell agglutination was inhibited by extracts of type 4 cells; strongly by hot acid-extract and partially by trypsin-extract. Hot acid-extract of type 41 cells had no inhibitory effect. Sandwich-enzyme-linked immunosorbent assay of the MAb and partially purified M-protein preparation combination against commercial T typing sera showed that only T-type 4 antiserum reacted with the combination system. From these data, we thought that the MAb preparations were not directed to M-protein but to T-protein of type 4, group A streptococci. PMID- 1919125 TI - [A study on the incidences of streptococcal infectious diseases in the regional surveillance informations of infectious diseases in Japan (2nd report)]. AB - The incidences of streptococcal infectious diseases in the regional surveillance informations of infectious diseases of 47 prefectures were compared with each other by the ratios of number of patients with streptococcal infectious diseases, exanthema subitum and varicella to the populations of surveyed age groups, respectively. It was estimated that although there were almost no regional differences in the ratios of exanthema subitum and varicella, the ratios of streptococcal infectious diseases were high in Hokkaido, Akita, Yamanashi, Shiga and Ehime Prefectures, respectively, and was low in Okinawa Prefecture. The corrected incidences of number of patients with streptococcal infectious diseases, calculated on the basis of the ratios of exanthema subitum and/or varicella, were also high in the regions of Hokkaido, Akita, Iwate, Nagano, Yamanashi, Gifu, Shiga, Okayama and Ehime Prefectures, respectively, and were low in the regions along the Pacific from the southern Tohoku (northern Japan) through a part of the Shikoku Island and the Sea of Japan from the Hokuriku (central Japan) through the Kyushu Island, and the regions of Nara and Okinawa Prefectures, respectively. The climate in the regions with high corrected incidence belonged to the Tohoku-Hokkaido, the Central Highlands and the Seto Inland Sea types, respectively. On the other hand, the regions with low corrected incidence belonged to the Tokai-Kanto, the Nankai (southern sea of Japan), the Hokuriku-Sanin, the Kyushu and the Okinawa climate types, respectively. PMID- 1919126 TI - [Antibiotic sensitivity and serotypes of group A hemolytic streptococci isolated from clinical specimens and healthy pupils in Japan, 1986-1988]. AB - As an epidemiological survey for streptococcal infection, antibiotic sensitivity test and T-serotyping were made on 2,735 strains of group A hemolytic streptococci isolated from clinical specimens and healthy pupils between 1986 through 1988 in Japan. Most dominant serotype in clinical isolates was T-4 (26.8%) and it was followed T-12 (25.5%), T-1 (11.2%) and T-3 (8.5%), on the other hand, dominant serotypes of the isolates from healthy pupils were T-12 (30.4%), T-1 (19.3%), T-4 (15.3%) and T-28 (13.4%). All of the isolates tested were sensitive to the beta-lactam antibiotics which was found as same as consequence of the previous surveys. However 36.4% to tetracycline, 2.1% to chloramphenicol and 1.4% to oleandomycin of the clinical isolates were resistant. Similarly, 16.2% to tetracycline, 2.3% to chloramphenicol 1.7% to oleandomycin, of the isolates from healthy pupils were resistant. Multi-resistant strains were found 1.4% in clinical isolates and 1.7% in the isolates from healthy pupils. Relation between distribution of multiresistant strain and T-serotypes was found. In T-12, multiresistant strains were encountered at a relatively high rate compared with other serotypes, representing 3.5% in clinical isolates and 5.6% in the isolates from healthy pupils. However this tendency was decreased than previous surveys, while incidence of tetracycline resistant strains in T-4 remained at high level, representing about 94% as same as in the past. PMID- 1919127 TI - [Isolation trends on group A streptococci isolated from clinical specimens in hospitals in Saitama, 1979-1989]. AB - On 4,864 group A streptococci isolated from throat culture of patients in hospitals in Saitama from 1979 to 1989, we have done an epidemiological analysis of the T-type detection rates and the T-type epidemic, the monthly isolation rates, and the isolation rates by sex and age of patients. 1. The T-type detection rates of 4,864 isolates of group A streptococci showed type T12 in 22.6%, type T4 in 16.4%, type T1 in 10.8%, type T13 in 8.5%, type T6 in 7.6%, type T28 in 6.9%, type T3 in 6.1% and type T18 in 5.3% etc, and the largest number of isolates was type T12 among 16 T-types. 2. The main epidemic T-type during the investigation was type T12, and it was at the top from 1980 to 1981 and from 1984 to 1985. The others, type T4 was at the top from 1982 to 1983 and from 1983 to 1989, type T3 was in 1986, type T6 was in 1987, and type T1 was in 1988, especially it has been suggested that there are the high epidemic T-types and low epidemic T-types among the T-types of throat group A streptococci. 3. Monthly epidemic pattern of throat group A streptococci in each year showed two small epidemic peaks on March and June, a large epidemic peak from November to December since a turn on August. Further, the monthly epidemic pattern has been repeated every year. 4. Throat group A streptococci isolated from patients occupied 87 per cent by the patients from 0 to 14 years, the peak of age distribution showed by age group from 5 to 7 years. The sexual ratio of male to female was in the ratio 1:0.9. Further, the throat group A streptococci isolated from patients of age greater than 15 years was occupied about 50 per cent by age group from 30 to 39 years. A sexual ratio of male to female in the age group was in the ratio 1:1.8. PMID- 1919128 TI - [Serotypes and antibiotic susceptibility of group A and B streptococci clinically isolated in Sapporo in the last five years]. AB - During the last five-year period between 1985 and 1989, serotypes of 671 strains of group A and 238 strains of group B streptococci isolated from clinical specimens in Sapporo city general hospital were studied. Results of serotyping were given as under; Type T4 (25.8%), T12 (25.6%), T1 (11.5%), T3 (9.2%), T6 and T28 (6.3% each), T8 and T22 (0.6% each), T13 (0.4%), T9 and B3264 were found in group A. Type T4 and T12 formed main types up to this time and T1, T3, T6 and T28 were other predominant types. The elevated isolation rates of type T3 and T28 were remarkable in this period. In group B, Ia (31.5%), III (16.8%), Ib (14.3%), II (8.0%) and V (4.2%) were observed. On 617 samples (391 group A, 226 group B) out of these strains, antibiotic susceptibility to 9 drugs were examined. No resistant strain (MIC greater than or equal to 25 micrograms/ml) to beta-lactam antibiotics was found in each group. Resistant strains in group A streptococci were demonstrated 24.3% to TC, 0.5% to OL. No resistant strain, however, was observed to CP or EM. In group B, resistant strains were found in 39.8% to TC, 6.6% to CP, 2.2% to EM. Strains resistant to only TC (31.0%) were most prevalent followed by TC.CP (6.2%) and TC.MLs (2.7%). Multi-resistant strain (to TC.CP.MLs) was not found. PMID- 1919129 TI - [Serotype and antibiotic susceptibilities of group A hemolytic streptococci isolated in Osaka, 1988-1989]. AB - A total of 386 strains of Group A hemolytic Streptococci isolated from the patients in Osaka in 1988 and 1989 were type-classified by both T-agglutination and M-precipitin methods and were examined for drug-sensitivity. The results were summarized as follows. 1. From T-typing result, T-1 (28.2%) was revealed as the most dominant serotype in 1988, followed by T-4 (24.9%), and T-12 (23.2%), although not as much difference was found in the isolation rate among these three types. A similar tendency was observed in the results of 1989. The order was T-4 (30.3%), T-1 (24.8%), and T-12 (22.1%). 2. In the isolated Group A hemolytic Streptococci, 177 out of 241 strains (73.4%) in 1988 and 126 out of 145 strains (86.9%) in 1989 were M-typable with seven kinds of M-typing sera (Anti-M-1, 3, 4, 6, 12, 13, 18). The result of M-typing was similar to that of T-typing, because the coincidence rate between T and M types was very high among the most prevalent serotypes such as 1, 4, 6, and 12 (type-1: 98.1%, type-4:89.4%, type-6:91.7%, type-12:94.3%). 3. The number of antibiotic-resistant strains decreased. It was especially prominent in the resistant strains to erythromycin, lincomycin and chloramphenicol. While the incidence of tetracycline resistant strains in type-4, 11 and 13 remained at a high level, it decreased in type-12 and 1. All strains were sensitive to the beta-lactam antibiotics. 4. No resistant strains were detected to enoxacin (ENX) and ofloxacin (OFLX), new quinolone. MIC90 values of ENX and OFLX were 16 micrograms/ml and 2 micrograms/ml, respectively, although difference of MIC90 was observed among some strain types: MIC90 of ENX against type-6 strain was 8 times higher than that against type-12 strain. PMID- 1919130 TI - [Serotypes and antibiotic sensitivity of hemolytic streptococci isolated from clinical specimens in Hiroshima Prefecture, 1987-1989]. AB - The grouping, the typing and the drug-sensibility of hemolytic streptococci isolated from the clinical specimens taken from 4 medical centers in Hiroshima Prefecture have been examined and reviewed during the past 3 years 1987-1989. The results were summarized in this report. 1. Of 1572 strains of hemolytic streptococci, 844 strains (53.7%) were group A; 539 strains (34.3%), group B; 14 strains (0.9%), group C; 82 strains (5.2%), group G; and 93 strains (5.9%), the others. We found that group A and group B were predominant, and the incidence rate of group B was higher than it used to be. 2. The prevalent types were T-4 (37.9%), T-1 (13.6%), T-12 (12.0%), and T-28 (10.7%) in group A, while Ia (26.2%), M9 (provisional type 18.4%), and III (14.5%) in group B. 3. As far as the detection data of each month is concluded, during the summer season we could hardly detect group A which peak of occurrence during the winter season. These findings were really consistent with the occurrence pattern of those patients who suffered from streptococcal infectious disease. But this occurrence pattern couldn't be found in group B. 4. In our study, the positive frequency was throat swab greater than urine greater than sputum greater than vaginal swab greater than pus greater than ear secretion in order. Group A was mainly isolated from throat swab, while group B, from several specimens including urine. 5. We found that there was a high drug-sensibility to the beta-lactam drugs in all strains except for 3 strains of group B which were resistant to CEX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919132 TI - [An epidemiological survey of group A, B, C & G hemolytic streptococci isolated from the Throat of Diabetic Children Streptococcicosis Study Group]. AB - The incidence of group A, B, C & G hemolytic streptococci residing in the throat of children with diabetes was surveyed. The survey was carried out in August, 1982 and August, 1983. Included in the surveys were 136 diabetic children. The survey was also carried out with healthy school children at the same term as the contrast. The detection rate of the streptococci among the diabetic children was significantly higher than the healthy school children. A great portion of streptococci detected from these diabetic children was classified into group B, on the other hand, from the healthy school children, group A. Although from healthy school children, BIII, BIa and several other types were isolated, from diabetic children only BIa and BIII were isolated. The detection rate of the streptococci among the diabetic children was significantly higher in the early days in camp for improvement of diabetes than in the last day. In the latter case the detection rate was similar to that among healthy children. In the other words following antidiabetic therapy as diabetes improved the detection rate were also improved. Among these 136 diabetic children examined 31 gave positive cultures at both surveys each year. Serogroups or serotypes in each year examinations, isolates, were identical in 26 cases. Most of these groups were group B and the types were Ia and III. PMID- 1919131 TI - A study of haemolytic streptococci isolated from outpatients in dermatological clinics. AB - A total of 44 patients suspected of streptococcal infections were studied in outpatient clinics in Tokyo during the one year from December 1988 to December 1989. Employing bacteriological culturing and serodiagnosis, the following results were obtained. 1) There were 9 cases of impetigo and 15 cases of erysipelas with typical clinical manifestations and age distributions. 2) It seemed that some of the skin infections were caused by group A streptococci whose M-types were different from those of upper respiratory infections typically occurring in Japan. 3) The type distribution of group A streptococci found were quite similar to those isolated in Thailand or Malaysia. 4) There were found group A streptococci exhibiting unique combinations of T- and M-types, such as T11 and M9, T11 and M62 or T13-49 and MOD8 (Provisional type). 5) As for serodiagnostic method, ADNB (anti-deoxyribonuclease B) titer reflected infection by group A streptococcus only, while ASK (anti-streptokinase) and ASO (anti streptolysin O) reflected not only group A streptococcal infections but group G infections as well. PMID- 1919133 TI - [Comparison between the aged and children of the normal distribution of pharyngeal and intestinal hemolytic streptococci]. AB - A marked difference between the aged and children has been observed in the group distribution of hemolytic streptococci isolated from various clinical specimens. Group B strains from the urine and sputum, and group G from the sputum, pus and exudate have been predominant in the aged, whereas group A strains from the throat swab have dominated in children. The present study was undertaken to clarify the background for such a marked difference by investigating the normal state of pharyngeal and intestinal carriage of hemolytic streptococci both in the aged and children. 1. As to the pharyngeal carriage, quite a contrast was observed between the aged and children. In the former, the rate of carries was low and the predominant groups among the streptococcus isolates were B (Streptococcus agalactiae) and G (identified as Streptococcus equisimilis), while in the latter, the rate was high and group A (Streptococcus pyogenes) strains comprised approximately 75% of the isolates, most of them being from the throat swab. 2. Both the aged and children showed a similar state of streptococcus carriage in the intestine. The rate of carriers was low and the predominant group among the isolates was B in both populations. Although group G strains were occasionally isolated, group A strains were isolated neither in the aged nor in children. These results explain well the difference between the aged and children in the group distribution of the clinical isolates of hemolytic streptococci. PMID- 1919135 TI - [Comparison between cultures of urine sediment and of the vagina for detection of carriers of group B Streptococcus (GBS) among pregnant women]. AB - An attempt was made to detect carriers of group B Streptococcus (GBS) among pregnant women by vaginal culture. Reported carrier rates have varied from 3% to 15% and one study has reported that cultures of urine sediment showed a very high positivity rate of 30% among non-pregnant women. In this study, we cultured urine sediment from 110 non-pregnant and 415 pregnant women. Among non-pregnant women, 26% were found to be GBS carriers by culture of urine sediment. Among pregnant women, the carrier rate was 3% by vaginal culture and 15% by culture of urine sediment. The serotypes of cases positive by vaginal vulture were identical with those positive by urine sediment culture. For detection of GBS carriers among pregnant women, culture of urine sediment is easy and reduces the rate of false negativity. PMID- 1919134 TI - [A study on hemolytic streptococci (group A, B, C and G) isolated from throat of the middle-aged and advanced-aged--especially as compared with elementary school children]. AB - Hemolytic streptococci were isolated from throat of middle-aged and advanced-aged and these organisms were classified into groups A, B, C and G. 1) Persons 15 to 39 years old were included in one group and persons from 40 years of age upward were divided into 5 groups every 10 years. Comparison of these groups were done. Generally, group B organisms were most often isolated. The detection rate of group B organisms was higher in the older age group. The detection rates of group A and G organisms were approximately equal, but both organisms were isolated from a few persons. No organism of group C was isolated from males, while only two strains belonged to group C organism were isolated from females. 2) A number of strains of group A hemolytic streptococci were isolated from school children, particularly in the lower classes. But the proportion of group B organism to isolated streptococci showed an increase in upper classes, noticeably in females. 3) For middle-aged and advanced-aged, blood samples were obtained simultaneously on examination of the throat, and ASO value and ASK titer were determined. ASO values were higher in persons infected with groups A, C or G organisms than in persons infected with group B organism or no hemolytic streptococcus. ASK titers revealed a similar results to ASO values, though the relation between ASK titers and isolated hemolytic streptococci was less positive. PMID- 1919136 TI - [A dying clinical diagnosis of scarlet fever--the last sixteen years survey]. AB - 11,119 patients with scarlet fever admitted in the last sixteen years, from 1973 to 1988, to Sapporo City General Hospital, were studied statistically on symptoms and laboratory findings. The results were summarized as follows: 1. Annual number of patients have reduced suddenly since 1981, and become zero in 1989. The patients increased in number during the winter season. Eighty two percent of the cases were between 3 and 8 years of age, and the average age was 5.8 year-old. 2. Cases of above-38 degrees C temperature were seen in about 81.4%, and from 2 to 5 days-duration of temperature were seen in 86.6% of the patients in the year 1976. Cases of above-moderate rash were observed in 68.2%, sever redness of throat in 29.9%, strawberry tongue in 86.3% and angular stomatitis in 37.7% of the patients. In recent statistical analysis (1982-1988), we found, however, a tendency that patients having stronger symptoms were being introduced to our hospital. 3. The higher rates of cases showing elevated ASD titer were seen in the elder patients and in the winter. C-reactive protein (CRP) titers were mostly in the range of (-) to (greater than or equal to 6+), having 2.4 + on an average. 4. Patients who developed into overt nephritis were not seen. Cases of microscopic hematuria (greater than or equal to 3 red cells/f in urine sediments), however, were observed in 1.1% (125/11,119). Sever complications were hardly seen. 5. Reappearance of beta-hemolytic streptococci (on a week after discharge) were found in 3.1% (241/7,877). 6. Reinfection or relapse cases of scarlet fever were found in 6.7% (642/9,585).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919137 TI - Relationships between thermal dose and heat-induced tissue and vascular damage after thermoradiotherapy of locally advanced breast carcinoma. AB - Twenty-four patients with locally advanced breast carcinoma were given thermoradiotherapy, and heat-induced damage to tissue and vasculature was studied in relation to thermal dose. Thermometry was performed using six to eight multi point thermistor probes. Heat-induced damage was quantified by histopathological analysis of biopsies taken from the temperature probe locations shortly after treatment. Both tumour and normal tissue were found in the biopsies. Fraction of tissue and fraction of vessels with heat-induced damage were determined for the malignant and the normal tissue compartment separately, using stereological techniques. Clear relationships were found between these parameters and the largest thermal dose achieved in one heat fraction. The data were subjected to logit analysis, and the thermal doses (eqv. min at 43 degrees C) that caused massive necrosis in 50% of the tissue were calculated to be 116 +/- 31 for the malignant tissue compartment and 205 +/- 49 for the normal tissue compartment. Similarly, the thermal doses that caused damage to 50% of the vessels were found to be 63 +/- 34 and 144 +/- 46 for the malignant and the normal tissue compartment, respectively. Thus, the tumour tissue was more sensitive to heat than was the surrounding normal tissue, irrespective of whether necrosis or vessel damage was considered. This was probably a consequence of physiological and vascular differences between the two tissue compartments. Evidence for primary and secondary cell death was found both in the malignant and the normal tissue, although primary cell death probably was of minor importance in the normal tissue. The data indicate that selective heat-inactivation of tumour tissue is possible by external microwave hyperthermia of locally advanced breast carcinoma. PMID- 1919140 TI - Effective estimation and computer control of minimum tumour temperature during conductive interstitial hyperthermia. AB - The goal of heat therapy in the treatment of malignant disease is to raise the temperature of all neoplastic tissue to a cytotoxic temperature for a predetermined period of time. This seemingly simple task has proved difficult in vivo in part because of non-uniform power absorption and in part because of non homogeneous and time-varying tumour blood flow. We have addressed this difficulty first by utilizing the conceptually simple technique of conductive interstitial hyperthermia, in which the tumour is warmed by multiple, electrically heated catheters, and second by implementing on-line control of minimum tumour temperatures near each catheter, estimated on the basis of the steady-state ratio of catheter power to catheter temperature rise. This report presents an analysis of the accuracy, precision, and stability of the on-line minimum temperature estimation/control technique for 22 patients who received 31 separate courses of conductive interstitial hyperthermia for the treatment of malignant brain tumours, and in whom temperature was monitored independently by 12-16 independent sensors per patient. In all patients the technique was found to accurately and precisely estimate and control the local minimum temperatures. Comparison of measured and estimated temperatures revealed a mean difference of 0.0 +/- 0.4 degrees C for those sensors within 1.0 mm of the expected location for minimum temperatures. This technique therefore offers an attractive method for controlling hyperthermia therapy-even in the presence of time varying local blood flow. PMID- 1919139 TI - Clinical research into hyperthermia treatment of cancer using a 430 MHz microwave heating system with a lens applicator. AB - Tokyo Metropolitan Komagome Hospital, Kyoto University Hospital, and Aichi Cancer Center used a lens applicator microwave equipment, the HTS-100, to treat 90 patients with a total of 96 tumours. The results were analysed, and the following conclusions reached. Three clinical cases have been presented to illustrate the features of the HTS-100. (1) The results of 383 heating sessions using the HTS 100 were analysed. Even tumours larger and deeper than 5 cm could be heated above 42 degrees C. The heating area is much wider than that of the other 2450, 915, 430 MHz microwave heating equipments. (2) Hyperthermia treatment using the HTS 100 was combined with radiotherapy. The percentage effectiveness in terms of CR+PRa was 66.3% for the 89 cases which could be evaluated. Even for tumours larger than 5 cm, and deeper than 4 cm, local control was achieved in 60.7%. Thus, the indications for microwave heating have been significantly expanded. (3) Combination of microwave heating and RF heating is a new protocol which also expands the indications for hyperthermia therapy. (4) The percentage of patients experiencing the side-effects of pain, a sensation of heat, and burns was 15.6%, 6.3%, and 3.6%, respectively. Most of these side-effects were mild and temporary. The percentage of patients experiencing pain was higher than in conventional microwave heating, probably because the area of heating was wider. (5) In the future, the HTS-100 can be expected to play an important role in clinical cancer hyperthermia. PMID- 1919138 TI - Pancoast tumour treated with combined radiotherapy and hyperthermia--a preliminary study. AB - Six patients with Pancoast (superior sulcus) tumours were treated with combined radiotherapy and hyperthermia from April 1986 to December 1989. Radiotherapy was performed using 10 MV X-ray, and all patients received total doses of 60-74 Gy, in five fractions per week, during 5.5-15 weeks. Hyperthermia was performed once or twice a week within 30 min after each irradiation, using 8 MHz RF capacitive heating equipment (Thermotron RF-8). Partial response, defined as 50% or more regression of the tumour, was observed in four of the six patients. Three patients are alive 30, 28, and 14 months after their treatments. Radiotherapy combined with hyperthermia appears to be a promising and effective means for treating Pancoast tumours. PMID- 1919141 TI - Dual-antenna applicator for hyperthermia of tumours at intermediate depth. AB - A dual-antenna applicator with 21 x 26 cm2 aperture, that is fully loaded and operates at 74 MHz, was developed at the Mallinckrodt Institute of Radiology. By placing two antennas into an applicator capable of propagating TE10 mode, a significant enlargement of heating pattern was achieved without an increase in applicator dimensions. When antennas are placed symmetrically about a parallel to the antenna axis of symmetry, the sensitivity of the applicator input impedance to variations of load impedance reduces. Stable coupling of the RF power to the treatment area may be provided. Twenty patients with eccentrically located tumours were treated using this device. PMID- 1919142 TI - A theoretical evaluation of the performance of the Dartmouth IMAAH system to heat cylindrical and ellipsoidal tumour models. AB - The Dartmouth interstitial microwave antenna array hyperthermia (IMAAH) system was evaluated based on its ability to heat idealized three-dimensional cylindrical and ellipsoidal tumour models with lengths between 2 and 16 cm. The evaluation was based on computer simulations of the three-dimensional temperature distributions produced by the explicit theoretical power deposition pattern of resonant dipole antenna arrays driven at 433, 915 and 2450 MHz. The theoretical calculations were performed using three-dimensional tumour models with constant thermal and dielectric tissue properties. Each 2 X 2 cm antenna array was evaluated on the basis of its ability to heat a specified tumour volume with various blood flow patterns. The bioheat transfer equation was solved in three dimensions using a Galerkin finite-element method. In general, under the conditions of this study, in all cases examined larger percentages of the ellipsoidal tumour volumes were heated to therapeutic temperatures (greater than or equal to 43 degrees C) than the cylindrical tumours. The 2450 MHz antenna array was the most effective at heating the shorter tumours, while the 433 MHz antenna array heated the longer tumours most effectively. The antennas driven at 915 MHz were most effective at heating the medium-length tumours, especially tumours with high blood flow. The results of this computerized comparative thermal dosimetry study provide information on the feasibility of modelling tumours as simple geometries, and serve to advance three-dimensional interstitial hyperthermia treatment planning. PMID- 1919143 TI - Evaluation of heating patterns of microwave interstitial applicators using miniature electric field and fluoroptic temperature probes. AB - The SAR patterns were determined for four commercially available microwave (915 MHz) interstitial applicators. Values of SAR were determined using a miniature (3 mm diameter) implantable isotropic electric field probe or a custom 0.25 mm diameter fluoroptic temperature probe. These are the smallest such probes that are currently available. Similar radial variation of SAR was found at the axial position of the gap in the outer conductor for each applicator. Electric field probe measurements are much faster and avoid some of the errors caused by the rapid spatial variation of SAR with interstitial applicators. The major limitation on the electric field probe is its size; it is larger than the applicators being tested. PMID- 1919144 TI - Evaluation of hypoxia and acidosis on the cytotoxicity of the stereoisomers of tetraplatin at normal and hyperthermic temperatures. AB - Tetraplatin is a second-generation platinum analogue that will be introduced into clinical trials during 1990. We have evaluated the cytotoxicity of tetraplatin and its stereoisomers under a variety of conditions in a human solid tumour cell line (A549). The d-trans stereoisomer of tetraplatin is the most cyutotoxic form of the drug under all conditions examined. Simultaneous treatment with hyperthermia (43 degrees C) resulted in a greater than 1 log increase in cytotoxicity over tetraplatin (10 micrograms/ml) alone. Lowering the pH of the media from 7.4 to 6.4 did not significantly modify the cytotoxicity of tetraplatin at 37 degrees C or at 43 degrees C. Under acidic pH (6.4) hypoxia did not alter the cytotoxicity of tetraplatin at 37 degrees C or 43 degrees C. These results indicate a potential therapeutic advantage of combining tetraplatin chemotherapy with hyperthermia, which appears to be uneffected by acidic and/or hypoxic conditions. PMID- 1919145 TI - Cytotoxic effect of 1,3 bis (2-chloroethyl)-N-nitrosourea at elevated temperatures: Arrhenius plot analysis and tumour response. AB - The effect of hyperthermia on the cytotoxicity of 1,3-bis-(2-chloroethyl)-N nitrosourea (BCNU) was investigated in vitro and in vivo. Tumour cells were early generation isotransplants of a spontaneous C3Hf/Sed mouse fibrosarcoma, FSa-II. For in vitro studies, single cell suspensions containing 1.0 x 10(6) cells/ml were treated in a water bath where a desired temperature was maintained by a constant-temperature circulator. Cell survival was determined by lung colony assay immediately thereafter. For in vivo studies the tumour cell suspensions were transplanted into the dorsal site of the C3Hf/Sed mouse foot. Tumours were treated by immersing animal feet into a constant-temperature water bath when tumours reached an average diameter of 4 mm (35 mm3). The tumour growth (TG) time or the time for one-half of the treated tumours to reach 1000 mm3 from initial treatment day was used as an endpoint. BCNU dose-cell survival curve at 37 degrees C was exponential with a D0 of 1.1 microgram/ml. Dose-cell survival curves at 37-43 degrees C were determined as a function of treatment time at pH 6.7 and 7.4. BCNU of 1 microgram/ml was added immediately before treatment. The slope of the survival curve became steeper with increasing temperature, indicating that the cytotoxic effect of BCNU was enhanced by hyperthermia. The Arrhenius plot analysis showed that activation energies at pH 6.7 and 7.4 were 53 and 51 kcal/M, respectively (no significant difference). Of interest in this analysis was that the Arrhenius plot did not show a breaking point which has been observed for other agents. Further investigation demonstrated that the decomposition of BCNU, which has been reported to be essential for production of reactive intermediates, occurred in aqueous medium at elevated temperatures. The magnitude of this decomposition depended on treatment temperature. As a result, preheated BCNU became less cytotoxic with an increase in preheating temperatures. The activation energy for this decomposition was about one-half of the activation energy for BCNU cytotoxicity. Studies in vivo indicated that the effect of BCNU was enhanced with increasing temperatures, and the enhancement was greatest when BCNU was administered i.p. immediately before hyperthermia. A glucose dose of 5 g/kg administered i.p. 60 min before hyperthermia further enhanced the antitumour effect of BCNU. PMID- 1919146 TI - Augmented antitumour effects of combined treatment with hyperthermia and tumour necrosis factor on human gastric cancer xenotransplanted into nude mice. AB - Hyperthermia combined with recombinant human tumour necrosis factor (rH-TNF) was evaluated for antitumour efficacy in vivo. Use was made of human gastric cancer tissues xenografted into nude mice. When 100, 300, 600, and 1200 units of rH-TNF (2.4 x 10(6) units/mg protein) were given twice intraperitoneally, tumour regression did not occur in any animal. In contrast, a remarkable suppression of tumour growth was observed when 600 and 1200 units of rH-TNF was given in combination with hyperthermia at 43.5 +/- 0.1 degrees C. No effects were evident with the regimen of 100 and 300 units of rH-TNF plus hyperthermia at the same temperature, as compared with evidence obtained with hyperthermia alone. The tumoral blood flow, determined by the hydrogen diffusion method, decreased immediately after hyperthermia alone or hyperthermia plus 1200 units of rH-TNF, whereas a slight decrease was seen after rH-TNF alone. When hyperthermia plus 1200 units of rH-TNF were given, there was a remarkable delay in reversion to pretreatment values of tumoral blood flow, as compared to findings with rH-TNF only or heat only. These results are discussed in relation to the antitumour and side-effects of rH-TNF. PMID- 1919147 TI - A comparison between the effect of step-down heating in a tumour and a normal tissue in vivo. AB - A comparison between the effect of step-down heating (SDH) obtained in a C3H mammary carcinoma grown in the feet of CDF1 mice and the skin of normal CDF1 feet is presented. Water-bath heating was used, and SDH was obtained by giving a 44.7 degrees C/10 min treatment followed by heating at 42.2 degrees C for variable times. Single heating at 42.2 degrees C and step-up heating (SUH), i.e. 42.2 degrees C followed by 44.7 degrees C/10 min, were used as controls. The endpoint was the heating time at 42.2 degrees C to obtain either a definite tumour growth time (TGT50) or a specific skin score level (RD50) in 50% of the animals. The effect of SDH and SUH was quantified by the step-down ratio (SDR), calculated as the ratio of the heating times at 42.2 degrees C to obtain the specific endpoint. In both assays the effect of SDH was seen as a significant left shift of the SDH dose-response curve compared to the curve for single heating and SUH. For the comparison of the tumour and the normal tissue response, damage levels with comparable heating times for single heating were used. The therapeutic effect was then investigated by calculating the therapeutic gain factor (TGF), where TGF = SDR(tumour)/SDR(normal tissue). Neither SUH nor SDH gave a TGF significantly different from 1. The results suggest that SDH may be used clinically to shorten the heating time without decreasing the therapeutic effect. PMID- 1919148 TI - Effect of hyperthermia on the in vitro hydrolysis of melphalan. AB - The pharmacokinetics of melphalan was investigated at 37 degrees C and 42 degrees C in vitro in canine and porcine plasma to assess heat-induced changes in the in vivo rate of melphalan hydrolysis. Melphalan concentrations were assayed using HPLC. Rate of spontaneous hydrolysis of melphalan at 42 degrees C was increased 1.5-fold in canine and 1.9-fold in porcine plasma. These results should be considered when interpreting in vivo disposition studies. PMID- 1919149 TI - Prevention of scald injury on the peritoneo-serosal surface in advanced gastric cancer patients treated with intraperitoneal hyperthermic perfusion. AB - In attempts to avoid the side-effects derived from a scald on the peritoneo serosal surface during intraperitoneal hyperthermic perfusion (IPHP) for advanced gastric cancer, a randomized study using cimetidine, a histamine H2-receptor antagonist, was carried out on 18 patients with advanced gastric cancer. Cimetidine, 50 mg/kg, was administered intravenously and immediately before IPHP. The background characteristics of the patients and the types of surgical treatment used were almost the same between each group of patients, whether or not cimetidine was given. The perfusion time in the cimetidine and control groups was 123 +/- 9 and 117 +/- 9 min, respectively. The inflow and outflow temperatures of the perfusate were 46.3 +/- 0.4 and 44.2 +/- 0.1 degrees C in the cimetidine group, respectively, whereas in the control group the temperatures were 46.0 +/- 0.3 and 44.1 +/- 0.2 degrees C, respectively. In the nine patients who were given cimetidine, the histamine concentrations in the peripheral blood increased significantly, compared to those in the nine controls; this resulted from the release of histamine into the circulating blood. Higher concentrations of protein were observed in the post-hyperthermic intraperitoneal exudate of the control group for 3-24 h after IPHP and, consequently, post-hyperthermic hypoproteinaemia was remarkable in the control group. These data suggest that when pre-IPHP cimetidine was prescribed for patients with gastric cancer treated with IPHP, the peritoneo-serosal surface was protected from scald injury and the side-effects of IPHP were reduced. PMID- 1919150 TI - Studies on endocrine changes induced by 8 MHz local radiofrequency hyperthermia in patients with bladder cancer. AB - To elucidate changes in hormone metabolism, especially thyroid, cortisol and sex hormone metabolism, during acute local heat stress, serum-free thyroxine (FT4), free tri-iodothyronine (FT3), reverse T3 (rT3), thyroxine binding globulin (TBG) and a number of other hormone levels [thyroid-stimulating hormone, thyroglobulin, calcitonine, luteinizing hormone, follicle-stimulating hormone, prolactin, growth hormone, cortisol and testosterone] were measured sequentially in 11 male patients with bladder cancer during and after local radiothermotherapy treatment. Hyperthermia was administered using 8 MHz radiofrequency (RF) capacity equipment. The core temperature was raised from 37 to 42 degrees C and maintained at 42 degrees C for 1 h. No significant change in hormone levels except for a slight decrease in TBG levels was observed. The clinical results indicated that 8 MHz RF hyperthermia at 42 degrees C can be applied safely as a therapeutic measure in patients with bladder tumours. Further studies concerning the changes in TBG are necessary in patients with other tumours, especially those with the complication of subclinical hyperthyroidism, to detect any corresponding rises in FT3 and FT4 levels. The effects of using higher temperatures also need to be examined. PMID- 1919151 TI - Phase I study of melphalan alone and melphalan plus whole body hyperthermia in dogs with malignant melanoma. AB - The maximum tolerated dose of melphalan combined with whole body hyperthermia (WBH) in dogs with spontaneous malignant melanoma was lower than in dogs not receiving WBH by a factor of 1.9 +/- 0.71. Thirty-three dogs were treated monthly with escalating doses of melphalan and followed weekly for toxicity and, when possible, tumour response. Toxicity was manifested as myelosuppression with nadir neutrophil and platelet counts occurring at 7-10 days post-treatment. The TD50 (+/- S.E.), defined by logistic regression analysis, was 0.63 (+/- 0.07) mg/kg and 0.33 (+/- 0.10) mg/kg for melphalan alone and combined with WBH, respectively. Objective tumour response in this limited series occurred in three of fourteen evaluable dogs (three of eleven treated with melphalan alone and none of three treated with WBH plus melphalan). It is concluded that melphalan combined with WBH can be safely administered, although a reduction in dose is necessary. A randomized clinical trial is required to investigate the possibility of achieving therapeutic benefit from combined melphalan and WBH. PMID- 1919152 TI - 3D rendering of SAR distributions from Thermotron RF-8 using a ray casting technique. AB - A comprehensive 3D visualization package developed for CT-based 3D radiation treatment planning has been modified to volume-render SAR data. The program accepts data from sequential thermographic thermometry measurements as well as calculated data from thermal models. In this presentation sample data obtained from a capacitive heating system 'Thermotron-RF8' is presented. This capability allows the generation of accurate standardized volumetric images of SAR and provides a valuable tool to better preplan hyperthermia treatments. PMID- 1919153 TI - Heating pattern of helical microwave intracavitary oesophageal applicator. AB - Helical microwave intracavitary oesophageal (HMIO) applicators were designed to operate at frequencies of 433 MHz and 915 MHz. Heating patterns were studied within muscle-equivalent phantom by thermographic camera and fibreoptic thermometers. The results showed that frequency significantly influenced the microwave heating pattern. The 433 MHz applicator had a single power deposition region, the longitudinal specific absorption rate (SAR) distribution appeared to be nearly even, and the maximum SAR value occurred close to the centre of the active length of the applicator. The 915 MHz applicator had two power deposition regions, the peak SAR values occurred at about 1/4 and 3/4 of the active length respectively. The radial SAR distribution suggested that there is no obvious difference between the 433 MHz and 915 MHz applicators in that the average radial penetration of 50% surface SAR (RP50) was about 0.65 cm. It was also shown that power deposition was axially symmetric for both 433 MHz and 915 MHz HMIO applicators. It is shown that better impedance matching is more important for intracavitary hyperthermia than for external hyperthermia. Choosing HMIO applicators in clinical practice is also discussed. PMID- 1919154 TI - Analysis and testing of a concentric ring applicator for ultrasound hyperthermia with clinical results. AB - A planar ultrasound transducer was modified by etching concentric circles on one surface of a piezoelectric ceramic to create four rings. The 10 cm diameter transducer had four active rings and an unenergized centre. The transducer housing was designed to be completely immersed in fluid, suitable for intraoperative hyperthermia. The transducer was resonant at 1.0 MHz and was tested in a water tank and in an acoustic absorbing medium where the steady-state temperatures were measured. A comparison between a single 10 cm element and the concentric ring modification with all rings at equal power density showed the performance to be nearly identical. In vivo experiments in canine thigh verified the phantom predictions as individual rings were energized. Theoretical intensity calculations were made and compared favourably to water tank test results. Clinical hyperthermia treatments for chest wall and head and neck tumours showed that the temperature distribution could be highly modified by adjusting the power to individual rings while holding the transducer stationary. Automated temperature mapping parallel to the transducer face was used to compare a single element applicator to the concentric ring applicator in clinical treatments on the same lesion. The concentric ring applicator was radially adjustable and was found to be advantageous in lowering the central peak temperatures and flattening the temperature distribution in tumours. A comparison between the single element clinical and operating room series showed that when pain is removed as a treatment limiting factor, higher central tumour temperatures are possible and more of the tumour volume achieves therapeutic temperatures. The concentric ring design improves the temperature distribution such that the higher central temperatures will not be necessary. PMID- 1919155 TI - Specific absorption rate steering by patient positioning in the 'Coaxial TEM' system: phantom investigation. AB - Cylindrical and elliptical homogenous phantoms were used to investigate, both theoretically and experimentally, the effect of phantom positioning on the specific absorption rate (SAR) distribution of the 'Coaxial TEM' system. Theoretical predictions indicated that the maximum of the SAR distribution was stationary around the central axis of the applicator system, irrespective of the position of the phantom. Therefore the maximum SAR can be located at different phantom sites as required. Although two-dimensional models give a qualitative insight in the phenomena studied, they lack quantitive agreement. The steering capacity has been confirmed experimentally and is now clinically applied by positioning the tumour mass according to these insights. PMID- 1919156 TI - Auditory brainstem response during systemic hyperthermia. AB - The relationship between the brain temperature and the latency of ABR was evaluated in a dog model of systemic hyperthermia induced by heating of the blood during extracorporeal circulation. The latency of ABR was shortened and the amplitude was reduced with the elevation of brain temperature. The shortening of the latency was more notable in wave 4 than in wave 1, and this is considered to have been due to greater changes in the conduction velocity in the central nervous system than in peripheral nerves. The latency of ABR, from which the brain temperature can be estimated, is considered to be clinically useful as an index of brain temperature during systemic hyperthermia. PMID- 1919157 TI - Effect of chronically induced thermotolerance on thermosensitization in CHO cells. AB - Chronic thermotolerance was induced in Chinese hamster ovary (CHO) cells by pretreatment at 40 degrees C for various times ranging from 15 min to 16 h. The thermotolerant cells were either exposed to single heat treatments at 43 degrees C or subjected to step-down heating consisting of a priming treatment at 43 degrees C for 90 min immediately followed by a graded test treatment at 40 degrees C. The results showed that chronic thermotolerance affected the thermal sensitivity of step-down-heated CHO cells in two ways: by lowering the effectiveness of the priming treatment at 43 degrees C and by reducing the response to the test treatment at 40 degrees C. The effect on the priming treatment corresponds to a reduction in the effective heating time, i.e. the thermotolerant cells respond as if they were exposed to 43 degrees C for times shorter than 90 min. It was further shown that, for a given conditioning treatment, the effectiveness of both the priming and the test treatment was reduced by the same factor; the thermotolerance ratios determined for 43 degrees C and 40 degrees C showed an identical dependence on the duration of the thermotolerance-inducing conditioning treatment. Since thermotolerance development did not reverse heat sensitization by step-down heating, it is concluded that thermotolerance and thermosensitization are distinct phenomena which act independently. PMID- 1919158 TI - Hyperthermia enhancement of radiation response and inhibition of recovery from radiation damage in human glioma cells. AB - Three human glioma cell lines were tested for the effectiveness of hyperthermia and thermal radiosensitization. Thermal sensitization was evaluated from the perspective of increased radiosensitivity as well as inhibition of recovery from radiation damage. The three glioma cell lines tested showed large shoulders on the radiation survival curve and a large capacity for recovery of potentially lethal radiation damage. Hyperthermia caused radiosensitization in all three cell lines, which was primarily characterized by the reduction of the survival curve shoulder with moderate decreases in the survival curve slope. The radiosensitization was dependent on the time and temperature of the hyperthermia treatment. At 45 degree C for 60 min the shoulder of the radiation survival curve could be completely eliminated and the degree of enhanced cell killing at the 2 Gy level ranged from factors of 10 to 20 under the various conditions. When hyperthermia was given to cells which were irradiated and then plated immediately, or delayed for 8 h before plating to allow recovery, hyperthermia was found to cause radiosensitization under both conditions. In addition, when the hyperthermia dose was increased the difference between the immediate plating and the delayed plating survival curve decreased and for 45 degrees C for 60 min this difference was completely eliminated, concomitantly with the elimination of the survival curve shoulder. These data indicate that hyperthermia may play a role in radiosensitization for the treatment of human glioma. PMID- 1919159 TI - Bacterial endotoxin lipopolysaccharide modulates synthesis of the 70 kDa heat stress protein family. AB - Murine bacillus Calmette-Guerin activated macrophages release several monokines when triggered by the bacterial endotoxin lipopolysaccharide (LPS); this has recently been reported to be strongly influenced by the sequence of hyperthermic and LPS treatments. In the work reported here, it was found that LPS treatment markedly modulated the rate of synthesis of proteins in the heat stress protein (HSP) 70 family in these macrophages. The rate of synthesis of the HSP 70 family was slightly reduced if the cells were incubated with LPS 4 h prior to heating at 43 degrees C for 1 h, but was greatly reduced as the triggering time approached the initiation of heating and was nearly completely abrogated if the LPS triggering immediately preceded or followed heating. Near-normal rates of HSP 70 synthesis occurred if the triggering was delayed until 1-2 h after the heating ended. The LPS-triggered release of tumour necrosis factor (TNF) was also reduced as the time of LPS addition approached the heating time, but this depressed release preceded the effects on HSP 70 synthesis and did not recover for up to 3 h after heating. The effects of LPS on HSP 70 synthesis also occurred in a murine monocytic cell line, PU5-1.8, which releases TNF in response to LPS, and in a murine fibroblast cell line, NIH/3T3. This indicates that these effects are not restricted to cells of monocyte or macrophage lineage. The nature of the transcriptional or translational mechanisms controlling these responses is unknown, but these data may contribute to the understanding of (1) the regulation of the HSP 70 family and (2) TNF processing in stressed cells. PMID- 1919160 TI - Augmentation of mouse natural killer cell activity by combined hyperthermia and streptococcal preparation, OK-432 (Picibanil) treatment. AB - It has previously been demonstrated that the local administration of OK-432 (Picibanil) enhances the response of a murine tumour and normal tissue to elevated temperatures. The experimental animals were C3Hf/Sed mice and the tumours were the fourth generation isotransplants of a spontaneous non immunogenic fibrosarcoma, FSa-II. The thermal enhancement ratio was greater for the tumour than for normal tissue, resulting in a favourable differential effect between normal and malignant tissues. Further studies were conducted to disclose the mechanism of OK-432 induced thermal enhancement. Although OK-432 showed a slight direct cytotoxic activity against tumour cells in vitro, the in vivo antitumour effect of combined OK-432 and hyperthermia treatments was greater than the effect expected from in vitro cytotoxicity, indicating the involvement of the host-mediated mechanisms. Whole body irradiation (WBI), which suppressed the host's immune reaction, did not affect the thermal enhancement mediated by OK 432, suggesting that radiosensitive cells (sensitive to WBI) were not involved in this process. As expected, the i.v. injections of the anti-mouse T-cell serum did not have any effect on the thermal enhancement of OK-432. The administration of blockers of the reticuloendothelium system, i.e. silica or trypan blue, did not inhibit the OK-432 induced thermal enhancement. Moreover, local intratumoural injections of normal or OK-432 induced macrophages showed no effect on tumour growth. The thermal enhancement by OK-432 was eliminated following treatments with anti-(asialo GM1) globulin. Despite the fact that the cytotoxic effect of anti-(asialo GM1) globulin was not selective to natural killer (NK) cells, all the experimental results indicated that NK cells were probably attributable to thermal enhancement by OK-432 in vivo. The NK cell activity was stimulated when the OK-432 was locally administered with hyperthermia. PMID- 1919162 TI - Modification of recovery from radiation damage by hyperthermia in yeast. AB - Recovery from radiation damage was studied in the diploid yeast Saccharomyces cerevisiae BZ 34 subjected to pre-irradiation, post-irradiation or simultaneous hyperthermic treatment. Pre-irradiation heat treatment at 51 degrees C for 20 m min sensitized the cells to lethal damage; however, these cells could efficiently recover from potentially lethal damage (PLD) on liquid holding. In contrast, post irradiation hyperthermia (51 degrees C for 20 min or 52 degrees C for 15 min) partially inhibited recovery from PLD. For treatments at 40 and 45 degrees C the inhibition of recovery was restricted to the duration of heat treatment. As soon as the temperature of the cells was reduced to 30 degrees C for 48 h, they showed a significant recovery from PLD. The kinetics of the liquid holding recovery of cells exposed to 600 and 900 Gy of radiation followed by heat treatment at 51 degrees C, 20 min or 52 degrees C, 15 min was studied. Post-irradiation heat treatment inhibits PLD repair (PLDR) during the first 3 h. Subsequent liquid holding for longer durations results in recovery from PLD, reaching a maximum of nearly 50% of that obtained in cells exposed to radiation alone. When the cells were held for 0-48 h between radiation and heat treatment, they showed recovery from radiation damage such that sensitization by subsequent heat treatment was reduced significantly over the 48 h interval. The inhibition of PLDR by hyperthermia also decreases progressively with an increase in the time interval between the two treatments. When both heat and radiation treatments were carried out simultaneously by irradiating the cells at 48 degrees C, the inhibition of PLDR was partial. The recovery factor, calculated as the ratio of survival after recovery to that on immediate plating (without PLDR), was 2.6 +/- 0.9 for simultaneous heat and radiation treatment compared to 11.9 +/- 2.7 for radiation alone. PMID- 1919161 TI - A study of the mechanism of hydralazine enhancement of thermal damage in the KHT tumour. AB - The mechanism of the potentiation of thermal damage by hydralazine (HDZ) has been investigated. Using the KHT sarcoma in the leg of C3H mice, it was shown that 5 mg/kg of HDZ given i.v. 15-20 min before irradiation or heat exposure: (i) increased the radiobiological hypoxic fraction from 1 to 32%; (ii) produced a greater than additive growth delay when combined with heating for 30 min at either 43 or 43.5 degrees C, or 60 min at 43 degrees C; (iii) produced only additive cell killing when combined with 30 min heating at 43, 43.5, or 44 degrees C, assayed by clonogenic cell survival immediately or 24 h after treatment; and (iv) produced a prolonged (greater than 72 h) reduction in relative tissue perfusion (RTP) in the tumour when combined with heating for 30 min at 43.5 degrees C. The effects of HDZ or heat alone lasted for less than 24 and 48 h, respectively. The RTP in skin was unaffected by either agent or combination of agents at the times assayed. The results show that this 30-fold increase in hypoxia does not increase the intrinsic thermosensitivity of KHT tumour cells, and that the prolonged reduction in RTP caused by the combined treatment is probably responsible, at least in part, for the greater than additive component of the measured growth delay in this system. The data suggest that non-perfused tumour vessels are more heat sensitive than perfused vessels. PMID- 1919163 TI - [A new method for analyses of sugar chains of glycoconjugates: the future prospects of pyridyl-amination]. PMID- 1919164 TI - [A second cell recognition site of fibronectin]. PMID- 1919165 TI - [Ornithine decarboxylase antizyme: a regulatory factor of the enzyme degradation]. PMID- 1919166 TI - [Involvement of GTP-binding proteins in phospholipase A2 activation]. PMID- 1919167 TI - [Rapid means of purity assessment of peptides by using capillary electrophoresis]. PMID- 1919168 TI - Antitumor immune surveillance by tumor necrosis factor producing cells. PMID- 1919169 TI - Effects of tumor-necrosis-factor-activated neutrophils on tumor cell survival. PMID- 1919170 TI - MHC class II-associated variation in the production of tumor necrosis factor in mice and humans: relevance to the pathogenesis of autoimmune diseases. PMID- 1919172 TI - [Sex steroids in therapy--historical developments]. PMID- 1919173 TI - [Genesis, progression and prevention of human cancers]. AB - Long-term studies of in vivo kinetics of growth and proliferation of human cancers in vivo have revealed that carcinomas become manifest in patients some 25 years after carcinogenetic process has begun (Fujita '78). During this long period of cancer growth, do cancer cells remain unchanged, in morphology and function? So far, few pathologists have attempted to answer the question. At late stages of cancer growth, human carcinoma cells show high degree of atypism so that correct diagnoses can always be established by microscopic examination of the atypism. By DNA quantification or karyotype analyses of individual cancer cells, however, we found that incipient cancers show much less DNA abnormalities than the advanced ones. It is now clear, from molecular studies (Fialkow '76) that, in principle, a human cancer starts from one mutated host cell. Histochemical studies revealed that the newborn cancer cell and their direct progeny, at least during the earliest stage of carcinogenesis, are diploid in DNA content and seem to show very little abnormalities. Obviously during the progression of cancer growth from the single cell to the final stage, gross changes are accumulated in the cancer cell genome so that highly atypical cells are constant final outcome of the human cancer growth in vivo. We analyzed abnormalities of chromosomal morphology together with DNA contents in advanced human cancer cells and found that, commonly, 10-20 chromosomal changes accumulate in individual cancer cells, thereby marked atypisms are produced in morphology and DNA contents in the cancer cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919175 TI - [Developmental sequence of fetal behavior and the functional development of the fetal central nervous system]. AB - The development of central nervous system (CNS) is the latest among the various fetal organs and is on the way to mature even at birth. Because behavior is the phenotype of the CNS function, the behavioral pattern significantly changes with the developmental stage of CNS throughout the whole fetal period. The purpose of this study is to clarify the developmental sequence of fetal behavior and to discuss the functional development of the fetal CNS. For the first step of this study, thirty-one normal pregnant women, between 20 and 41 weeks of gestation, were examined for 60 minutes by using four ultrasonographic machines, which were employed simultaneously for observing four parts of each fetus: head, trunk, upper and lower extremities. All fetal movements were categorized according to the moving parts of the body and the peculiarities of movement. Trunk movements include six types i.e. flexion, stretch, rolling, startle, jumping (stepping), and writhing. The peak incidences of flexion and stretch were in 28-31 weeks of gestation. The incidence of rolling movements was high in 24-27 weeks, thereafter lowered gradually with gestational age, and then showed the significant increase in 40-41 weeks. The incidences of startle and jumping movements were high before 28 weeks, and then decreased significantly. Writhing movements were often observed after 28 weeks. The other movements showed the respective patterns of the changes in the incidence. Secondly, animal experiments were performed to obtain the basic data on fetal behavior which could not be given by the ultrasonographic observation of human fetuses. Fetal goats were incubated under the physiological condition in artificial amniotic fluid by using extracorporeal membrane oxygenation (ECMO) system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919174 TI - [Significance of radiotherapy in the multidisciplinary treatment of gynecological malignant tumor]. AB - Effectiveness of radiotherapy and measures for improvement of treatment were examined with regard to cervical cancer, endometrial cancer and ovarian cancer, for (1) adenocarcinoma, (2) metastatic cancer, and (3) cancer in persons of advanced age. I. (1) The prognosis of cervical adenocarcinoma is poor, but radiotherapy in combination with chemotherapy can be expected to be effective for the poorly differentiated type, metastasis to the lymph node, and deep cervical invasion. (2) Radiotherapy has limited effectiveness for endometrial cancer and needs to be employed in combination with chemotherapy for the poorly differentiated type adenocarcinoma, serous adenocarcinoma, deep uterine wall invasion, vascular invasion, and metastasis to the lymph nodes. (3) In regard to cervical cancer and endometrial cancer, identification and computation of the labeling index of S-phase cells by BrdU and examination of the localization and the changes in the appearance of tumor markers and oncogenic products showed radiosensitivity of adenocarcinoma to be poor. (4) For ovarian cancer, whole pelvic irradiation by the moving strip (MS) method in combination with chemotherapy showed satisfactory results for stage I and stage II cancers. For stage III cancers, the results was not satisfactory when the residual tumor was 2 cm or larger in size. Whole pelvic irradiation of 50-TDF or more is necessary in such cases. II. The prognosis in cases of metastasis to multiple pelvic lymph nodes is poor. For such cases, it is desirable to employ paraaortic irradiation in combination with chemotherapy, with consideration of the histologic type and progress of the cancer. III. The prognosis is poor in persons of advanced age of 70 or over.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919176 TI - [Ontogeny of behavioral patterns in relation to the concurrent development of central nervous system function, focusing on REM sleep, NREM sleep and waking states in the human fetus]. AB - Behavior is considered a one to one match between the manifestation of a particular individual motor activity (movement) and its correlated brain function. Each motor activity can be seen to run on its own developmental course with advance in gestation, while various movements also develop in concurrence with one another during intrauterine life, gradually integrating into complex and accommodated movements. I emphasized the present study, under real-time ultrasound observation, for investigating whether or not three states: REM (rapid eye movement) sleep, NREM (non-rapid eye movement) sleep and the waking state actually exist in utero, and if so, when the development of these states begins. 1. Examined for 30-40 minutes were 21 fetuses, including 10 from 33 to 36 weeks of gestation and 11 from 37 to 41 weeks of gestation. As parameters, the duration of each eye movement unit and the cumulative duration of this movement, from the shortest to a given duration, per individual case, were observed. A scattergram of cumulative duration vs, given duration obtained from all cases, for each age group, were analyzed using "piecewise linear regression". Critical points were noted, with statistical significance, at 0.62 second for the earlier group and at 0.76 second for the later group. These findings reveal two different types of eye movement: rapid and slow eye movements. The fact that the rapid eye movement coexists with the slow eye movement during REM period indicates that REM sleep exists in utero at the latest at 33 weeks of gestation. 2. Observed for 60 minutes were 26 fetuses from 28 to 41 weeks of gestation. Regular mouthing movement every 300 to 600 msec concurred significantly only with the NREM period from 35 weeks of gestation onwards. Random mouthing movements were observed predominantly during REM sleep and were unrelated to the advance in gestational age. This concurrence between the NREM period and regular mouthing indicates the existence of NREM sleep in utero at this age of gestation. 3. To evaluate whether the waking state is present, 10 fetuses at 36 weeks or more of gestation were examined for a concurrence between miosis/mydriasis and the REM/NREM periods. Using pupil diameter as a parameter, miosis and mydriasis were distinguished from each other, statistically, by means of "least median of squares regression". Accordingly, the NREM period was occupied only by miosis (41.0% of total observation period), while the REM period was divided into two conditions: 52.6% with miosis and 6.4% with mydriasis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919171 TI - Regulation of tumor necrosis factor production by monocyte-macrophages and lymphocytes. PMID- 1919177 TI - [Studies on features of fetal movement and development of human fetus with use of fetal actogram]. AB - In 167 normal fetuses at 26 to 41 weeks of gestation, features of fetal movement and fetal development were investigated with use of actocardiograph in connection with a microcomputer system. The signals of fetal movement obtained by actocardiograph were stored in a floppy disc every 250 ms for 5 minutes through an AD-converter, and were analyzed every 5 minutes with the computer to reveal 3 dimensional (3-D) histograms. The 3-D histogram of fetal movement was composed of number, amplitude and interval of the signals in 11 voltage steps between 0.05 and 0.55V. The histogram clearly indicated state of fetal behavior, being either resting or active state. Fetal movement such as rolling movement, breathing movement and hiccup could be also identified with the computer analysis. In 68 normal fetuses at 14 to 41 weeks of gestation, the cross-correlation between fetal movement and fetal heart rate (FHR) were examined with the computer analysis. Finally fetal responses to acoustic and light stimulation were evaluated with use of pure-tone generator and flashlight. Acoustic stimulation was carried out in 53 normal fetuses at 28 to 41 weeks and light stimulation was performed in 116 normal fetuses at 18 to 41 weeks of gestation. The fetal responses were evaluated with actocardiogram. As a result, 1) Frequency in active state decreased and resting state increased as gestational weeks advanced, and then the frequencies of both state remained constant after 37 weeks of gestation. Duration of resting state also increased from 26 weeks to 37 weeks. These observations may suggest that fetal behavior can be established by 37 weeks of gestation. 2) Frequency in rolling movement decreased until 37 weeks of gestation, and then the movement increased during 38-41 weeks. Frequency in breathing movement increased to 33 weeks of gestation, then it remained constant. Hiccup occurred most frequently at 30-33 weeks, and it decreased thereafter. The function in fetal respiratory movement may be accomplished by 33 weeks of gestation. 3) Positive cross-correlation between fetal movement and FHR was observed as gestational weeks advanced. The correlation coefficient increased from 14 weeks up to 41 weeks. Acceleration of FHR following fetal movement eventually occurred in fetuses at 16 weeks, but the onset of acceleration delayed than normally occurred in developed fetuses. The delay was shortened in fetuses at 24 weeks and this was comparable to the delay in developed fetuses. These results suggest that the linkage of the acceleration of FHR with fetal movement is established at 24 weeks of gestation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919179 TI - [Ultrastructural studies of mucosal epithelium in histological internal os of human uterus]. AB - The surface epithelium of the mucosal lining of the histological internal os (HIOs) in the human uterine cervix was examined by scanning (SEM) and transmission electron microscopy (TEM). By SEM, the ultrastructure of the surface epithelium of HIOs was seen to be quite different from that of the usual endocervical and endometrial epithelium: The epithelia of HIOs were flat and found to be composed of various sizes and shapes of epithelial cells. Most of the epithelial cells had poorly developed microvilli, and the following characteristic patterns of cell arrangements: Funicular arrangement of spindle shaped cells, pavement-like arrangement of small round cells and relatively large flat multiangular cells and island-like accumulation of cells whose surface was elevated like a dome. TEM observations revealed that most of the epithelial cells might be functionally undeveloped. However, some epithelial cells developed into mucus-secreting cells, and others resembled endometrial glandular cells. Some of the cells which resembled the endometrial glandular cells had an accumulation of glycogen granules in the subnuclear region in the early secretory phase. There were no cyclic morphological changes on the surface epithelium of HIOs during the menstrual cycle, except for the accumulation of glycogen granules in a few cells in the early secretory phase. PMID- 1919178 TI - [The fetal diseases--recent advances in the fetal diagnosis and therapy]. AB - To know the pathophysiological conditions of the fetus as a patient is very important for the determinations of methods of fetal diagnosis and therapy. The mechanisms by which maternal infection triggers the uterine contraction are poorly under stood. Firstly, we investigated the role of maternal endotoxin and heat stress. Studies were carried out in 6 chronically prepared, pregnant goats or sheep at 129 to 137 days gestation. Blood samples were collected for determinations of plasma interleukin-1, PGF2 alpha, cortisol and catecholamines levels from mother and fetus after infusion of 1.0 mg E. Coli endotoxin into the maternal jugular vein. From these animal experiments, it is demonstrated that maternal interleukin-1 PGF2 alpha levels tended to rise, and these endocrinological or interleukin-1 changes induced the uterine contraction during maternal hyperthermia. Recently, diagnostic technique in detections of fetal diseases have undergone a major revolution by the appearance of real-time ultrasound, predictive genetic testing using DNA prove and cordocentesis. Drug therapy and surgical therapy in the fetus have also undergone considerable changes, however, previous attempts at therapy have been generally unsatisfactory and rarely successful. Recently, we performed a new technique for dead fetus removal in utero by selective cesarean in a case of monochorionic monoamniotic twin pregnancy with intrauterine death of one twin at 28 weeks' gestation. The patient was delivered by re-cesarean section at 33 weeks' gestation on five weeks after first surgery was hospitalized for small-for-dates. Ethics in the development of fetal diagnosis and therapy are controversial. We never forget to gain from parents the informed consent. PMID- 1919180 TI - [Blood coagulation and fibrinolysis activities during normal pregnancy and fetal growth--study based on estimated fetal body weight]. AB - There are many factors influencing the growth of the fetus. Since these factors have complex interrelations, they are difficult to clarify. The authors studied the effects of blood coagulation and fibrinolysis on the growth of the fetus during pregnancy, especially from the 2nd trimester into the 3rd trimester. The subjects were 86 normal pregnant women, and the subjects of study were blood coagulation, fibrinolysis activity of the mother, and estimated fetal birth weight after the 28th (2nd trimester) and 36th weeks of gestation (3rd trimester) in each case. 1. Changes in blood coagulation activity and fibrinolysis varied from the 2nd trimester into the 3rd trimester. The percentage of cases showing lowered platelets was 68.6% of the total, and the percentages of cases with reduced platelet ADP, epinephrine, and collagen aggregation were 60.5%, 55.8%, and 51.2%, respectively. The percentages of cases showing shortened prothrombin time and activated partial thromboplastin time were 58.1% and 51.2% of the total, respectively. The percentage of cases with reduced fibrinogen was 24.4% of the total. The percentages of cases with reduced antithrombin III, plasminogen, and alpha 2-plasmin inhibitor activity were 66.3%, 55.8%, and 75.6% of the total, respectively. 2. The birth weight of babies in a group with shortened prothrombin time was 2,935.1 +/- 395.2g(n = 50, mean +/- SD), while that in a group with prolonged prothrombin time was 3,106.2 +/- 357.9g(n = 36). The estimated fetal birth weight gain from the 2nd trimester to the 3rd trimester was 1,431.6 +/- 296.5g in the former group and 1,644.5 +/- 390.5g in the latter group. The differences were significant (p less than 0.05, p less than 0.01). The birth weight of babies in a group with lowered antithrombin III activity was 2,960.1 +/ 341.3g(n = 57), and that in an acceleration group was 3,157.8 +/- 370.0g(n = 29). The estimated fetal weight gain from the 2nd trimester to the 3rd trimester was 1,477.7 +/- 281.9g in the former group and 1,637.1 +/- 390.6g in the latter group. The differences were significant (p less than 0.02, p less than 0.05). 3. The estimated fetal weight gain from the 2nd trimester to the 3rd trimester in the group showing prolongated prothrombin time and activated partial thromboplastin time in this period was significantly larger than in the group showing shortened prothrombin time and activated partial thromboplastin time (p less than 0.001). These results suggested that the changes in blood coagulation and fibrinolysis activity of mothers from the 2nd trimester to the 3rd trimester affected the growth of the fetus. PMID- 1919181 TI - [Immunohistochemical studies of ras oncogene product p21 in 7,12 dimethylbenz (a) anthracene-induced rat ovarian tumors]. AB - In the present study, ras oncogene product p21 was analyzed immunohistochemically in rat ovarian tumors induced by 7,12 dimethylbenz (a) anthracene (DMBA). 1) After 28-38 (average 35.6) weeks, the tumors -6 adenomas, 30 adenocarcinomas, 3 sarcomas, one mixed mullerian tumor and 2 epidermal cysts--were produced in the rat ovaries. 2) The p21 positive reactions could be seen in the cytoplasm of the tumor cells. The positive rates were as follows: adenomas 83%, adenocarcinomas 57%, sarcomas 67%, mixed mullerian tumors 0%, epidermal cysts 100%, in which the positive reactions were obtained in squamous cells. Both of the serial allografted tumor and DMBA-OC-1 were positive. 3) The present study showed that the ras oncogene is not a specific gene in ovarian sarcoma or in other tumors. 4) The present study has suggested that the ras oncogene plays a role in tumor genesis including benign tumors, by showing p21 positive in adenomas and epidermal cysts. PMID- 1919182 TI - [Changes in serum androgen levels in patients with polycystic ovary syndrome]. AB - In order to study the changes in androgen levels in patients with polycystic ovary syndrome (PCOS), serum androgen levels (testosterone [T], free-testosterone [free-T] and sex-hormone-binding globulin [SHBG]) were measured and related to the incidence of menstrual abnormalities, obesity and hirsutism. Tests were made in 61 cases of PCOS identified by transvaginal ultrasound and in normal controls. The following results were obtained: 1) The PCOS group with menstrual irregularities had significantly higher levels of T and free-T than the control group, but SHBG levels were not significantly altered. 2) The obese group had significantly higher free-T levels than the non-obese group, and SHBG was significantly lowered. 3) There were significant correlations between the levels of obesity and free-T and SHBG. 4) T and free-T were moderately high in the hirsutism group and SHBG was moderately low, but not significantly so. These findings indicate that, in PCOS patients, serum androgen levels, especially free T and SHBG, are closely related to menstrual irregularities and the level of obesity. PMID- 1919183 TI - [Epidemiologic and clinicopathologic studies of partial hydatidiform mole]. AB - To determine the epidemiological and clinicopathological characteristics of partial hydatidiform mole (PHM), a comparative study of PHM and complete hydatidiform mole (CHM) was performed in molar patients who were entered in the regional registry of Niigata Prefecture and/or who were admitted for treatment at Niigata University Hospital. The results obtained are as follows. 1. From 1971 to 1988, 2,290 hydatidiform moles (HMs) were documented in the registry. The incidence of HM was annually decreasing with an almost constant ratio to the total number of pregnancies. Since 1986, the number of PHM was rising with an inverse decrease in CHM. One hundred fifty one of 1,923 CHM (7.9%) had persistent trophoblastic disease (PTD), but on the other hand only 6 of 367 cases PHM (1.6%) had. 2. In 275 patients treated in our hospital from 1971 to 1990, 134 of 240 with CHM (55.8%) and 6 of 35 with PHM (17.1%) experienced PTD. Of 6 PTD patients following PHM, 3 had invasive mole, 1 metastatic mole and 2 post molar persistent hCG, but no choriocarcinoma. 3. The recent study of DNA analysis in molar tissue revealed that one case, which had been diagnosed as PHM, coexisted with CHM and non-molar pregnancy. PMID- 1919184 TI - [Case-control study of the effectiveness of mass screening in reducing invasive cervical cancer]. AB - A case-control study was conducted in Miyagi Prefecture, Japan, to evaluate the effectiveness of mass screening for invasive cervical cancer. The Papanicolaou (Pap) smear histories of 109 cases with invasive cervical cancer diagnosed in the years 1984-1989 were compared with those of 218 age (+/- 3 years)- and area matched controls. Fifty-five percent of 109 cases were screened at least once, while for the controls the figure was 85.5%. Compared with women who were never screened, the odds ratio of invasive cervical cancer for women screened at least once was 0.16 [95% confidence interval: 0.090-0.278]. The odds ratio for 98 cases with squamous cell carcinoma for screened versus never screened women was 0.14 [0.080-0.253]. The Pap smear was less effective as a screening procedure for adenocarcinoma of the cervix than for squamous cell carcinoma. Of 11 cases with adenocarcinoma, 81.8% were screened, compared with 90.9% of controls. The odds ratio was 0.45 [0.054-3.719]. It showed that the odds ratio for the 1-year interval between last normal smear and diagnosis was 0.11 [0.061-0.196] and that for the 2-year intervals was 0.33 [0.157-0.714]. From the results of our study, it can be concluded that mass screening is effective for invasive cervical cancer. PMID- 1919185 TI - [Fertilizing capacity of fresh and frozen spermatozoa]. AB - Although frozen semen is now being used clinically, the fertilizing function of thawed semen has not yet been evaluated adequately. The changes in frozen sperm functions were evaluated and the changes in regard to the fertilization phenomenon were also investigated. The collected semen was evaluated by the following function tests, 1) Bovine cervical Mucus Penetration test (BMP test), 2) Zona-free hamster egg Sperm Penetration Test (ZSPT), 3) Hypoosmotic Swelling test (HOS test), 4) Triple stain technique (AR test), 5) Semen Auto Analyzer. The freezing medium was KS-II solution with a program freezer (CRYO-10). The results were as follows: 1) In the BMP test, the frozen normospermic group maintained fertilizing capacity. 2) There was no significant difference between fresh and frozen semen in the penetration rate of ZSPT except in the oligospermic group. 3) In the HOS test, there was no difference between fresh and frozen specimens in the number of swollen sperms which endured freezing and maintained the sperm membrane integrity. 4) There was a tendency to compare to that of fresh semen the increase in AR in frozen semen, but it was not significant. 5) There were low values after thawing except for LHD, but there still remained fertilizability after freezing. In conclusion, there was no reduction in fertilizing capacity following freezing through out the sperm function tests. PMID- 1919186 TI - [Amplified DNA detection of HPV types 16 and 18 DNA in cervical scrapes by polymerase chain reaction]. AB - Cervical scrapes from 43 patients (12 with chronic cervicitis, 13 with dysplasia, 11 with carcinoma in situ and 7 with invasive carcinoma) were examined by the polymerase chain reaction (PCR), to detect the amplified E7 gene of the HPV types 16 and 18 DNA sequence. HPV types 16 and/or 18 DNA were detected in 25 of 43 cases by the PCR (type 16 in 16, type 18 in 8, and both types 16 and 18 in 1). In comparison with the results for histological grades, the positive rate significantly increased as the grade of cervical dysplasia became higher. All cases were also examined with a HPV detection kit, the "Vira Pap" which contains 32P-labeled mixed RNA probes complimentary to HPV types 6, 11, 16, 18, 31, 33, 35 DNA. Six of 18 cases in which HPV DNA were not detected by the Vira Pap were positive for HPV types 16 and/or 18, so that the PCR was a highly sensitive method compared to the Vira Pap. The PCR has some advantages: 1. it requires only a small amount of specimens and 2. paraffin-embedded sections can also be used. We suggest that the PCR is a useful method for the screening and for retrospective investigation of HPV infection. PMID- 1919187 TI - Effect of vasoconstrictor and vasodilator on isolated human umbilical vein. AB - The mechanical properties of the longitudinal and circular muscle tissues of the human umbilical vein and the effects of nicardipine were investigated. Spontaneous contractions were observed in the isometric condition. When high concentrations of potassium (118mM-K+), oxytocin and serotonin were applied, these substances evoked contractions. Oxytocin (10(-4)-10(-2) U/ml) enhanced the spontaneous contractions. Serotonin produced contractions at 10(-9)-10(-4) M in both the longitudinal and circular muscle strips. When nicardipine (10(-5) M) was applied, contractions induced by 118mM-K+ were completely inhibited, but contractions induced by serotonin could not be completely abolished, i.e., tonic contractions ceased but small phasic contractions continued. Nicardipine (10(-8) M) did not inhibit the amplitude and frequency of spontaneous contractions, but decreased the basal tonus. These results suggested that nicardipine might improve feto-placental blood flow while decreasing the spontaneous basal tonus. PMID- 1919188 TI - [Detection of HPV type 16 early genes E7 and E5 messenger RNA in uterine cervical neoplasia by reverse transcriptase polymerase chain reaction]. PMID- 1919189 TI - Can ritodrine hydrochloride suppress the bone marrow function? PMID- 1919190 TI - [Adenosquamous carcinoma arising in benign cystic teratoma of ovary]. PMID- 1919191 TI - [Transient diabetes insipidus complicated with liver dysfunction during pregnancy]. PMID- 1919192 TI - In vitro fertilization using epididymal spermatozoa for the patients with obstructive azoospermia. PMID- 1919193 TI - [Mechanism of hemostasis and thrombosis formation]. PMID- 1919194 TI - [Diagnosis of hemorrhagic diseases and thrombosis. Platelet function tests and their problems]. PMID- 1919195 TI - [Diagnosis of hemorrhagic and thrombotic diseases. Mechanism of blood coagulation and their problems]. PMID- 1919196 TI - [Fibrinolytic tests and the related factors]. PMID- 1919197 TI - [Vascular function tests for diagnosis of blood coagulation disorders]. PMID- 1919198 TI - [Diagnostic procedure of hemorrhagic diseases]. PMID- 1919199 TI - [Diagnostic procedure of thrombosis]. PMID- 1919200 TI - [Physiopathology and therapy of platelet function disorders]. PMID- 1919202 TI - [Physiopathology and therapy of disseminated intravascular coagulation]. PMID- 1919201 TI - [Physiopathology and therapy of hemophilia and von Willebrand's disease]. PMID- 1919203 TI - [Progress on thrombolytic treatment]. PMID- 1919204 TI - [Blood component transfusion therapy]. PMID- 1919205 TI - [Diagnosis and therapy of thrombosis]. PMID- 1919206 TI - [A case of Cushing's syndrome due to bilateral adrenocortical adenoma]. PMID- 1919207 TI - [A case of nephrotic syndrome associated with eosinophilic angiolymphoid hyperplasia]. PMID- 1919208 TI - [A case of non-cardiogenic pulmonary edema following non-ionic contrast media injection]. PMID- 1919209 TI - [Clinical characteristic of mild hemophilia A]. PMID- 1919210 TI - [Diagnosis of arrhythmia]. PMID- 1919211 TI - [Diagnostic procedure of arrhythmia]. PMID- 1919212 TI - [Classification of arrhythmia]. PMID- 1919214 TI - [Clinical application and significance of cardiac electrophysiological tests]. PMID- 1919213 TI - [Actual condition of arrhythmia observed by Holter electrocardiography]. PMID- 1919215 TI - [Diagnosis and physiopathology of supraventricular tachycardia]. PMID- 1919216 TI - [Diagnosis and physiopathology of ventricular tachycardia]. PMID- 1919218 TI - [Physiopathology and diagnosis of bradycardia]. PMID- 1919217 TI - [Physiopathology and diagnosis of arrhythmia complicated with WPW syndrome]. PMID- 1919219 TI - [Therapy of arrhythmia with coronary diseases]. PMID- 1919220 TI - [Therapy of arrhythmia with cardiomyopathies]. PMID- 1919222 TI - [Clinical application and types of cardiac pacemakers]. PMID- 1919221 TI - [Clinical characteristics of arrhythmia in the aged]. PMID- 1919223 TI - [Clinical application of catheter ablation in the treatment of arrhythmia]. PMID- 1919224 TI - [Therapy of arrhythmia in outpatients]. PMID- 1919225 TI - [A case of myasthenia gravis complicated with severe aplastic anemia]. PMID- 1919227 TI - [A case of adrenal myelolipoma]. PMID- 1919226 TI - [Familial outbreak with hypersensitivity pneumonitis]. PMID- 1919228 TI - [A case of Wegener's granulomatosis of the lung diagnosed by open-chest lung biopsy]. PMID- 1919229 TI - [A case of hypersensitivity angitis associated with pulmonary infarction and tibial artery occlusion]. PMID- 1919230 TI - [Classification and etiology of hyperlipoproteinemia]. PMID- 1919231 TI - [Concept of diabetes mellitus and the diagnostic criteria]. PMID- 1919232 TI - [Mechanism of insulin insufficiency and classification of diabetes]. PMID- 1919233 TI - [Recent study of contributory factors to diabetes mellitus]. PMID- 1919234 TI - [Differential diagnosis of impaired glucose tolerance]. PMID- 1919235 TI - [Etiology of diabetic complications and the clinical conditions]. PMID- 1919236 TI - [Targets in the treatment of diabetes mellitus]. PMID- 1919237 TI - [Application of oral hypoglycemic agents in the therapy of diabetes mellitus]. PMID- 1919238 TI - [Clinical application of insulin in the therapy of diabetes mellitus]. PMID- 1919239 TI - [Control of borderline cases of impaired glucose tolerance]. PMID- 1919240 TI - [Differential diagnosis of coma in diabetes and their therapy]. PMID- 1919241 TI - [Prevention and countermeasure of diabetic complications]. PMID- 1919242 TI - [Education of diabetic patients]. PMID- 1919243 TI - [Insulin gene and its abnormality]. PMID- 1919244 TI - [Structure and function of insulin receptor]. PMID- 1919245 TI - [Structure and function of glucose transporter protein]. PMID- 1919246 TI - [Genetic diagnosis of diabetes mellitus]. PMID- 1919247 TI - [Pancreas transplantation and simultaneous pancreas-kidney transplantation in the therapy of diabetes mellitus]. PMID- 1919248 TI - [Prevention of diabetic complication and target in control of diabetes mellitus]. PMID- 1919249 TI - [A case of ulcerative colitis showing anti-Rh (e)autoantibody associated with autoimmune hemolytic anemia]. PMID- 1919251 TI - [A case of malignant lymphoma associated with polymyositis]. PMID- 1919250 TI - [A case of aortitis syndrome with complete left coronary artery obstruction and collateral circulation between the sinus of Valsalva and left coronary artery]. PMID- 1919252 TI - [A case of anaphylactic shock with coronary vasospasm]. PMID- 1919253 TI - [A case of basilar artery migraine]. PMID- 1919254 TI - [Cell communication between leukocytes and vascular endothelium cell by adhesion molecules]. PMID- 1919255 TI - [Vascular endothelium cell-derived vasodilative and vasoconstrictive factors]. PMID- 1919256 TI - Endometrial cultures and their application to new reproductive technologies: a look ahead. PMID- 1919257 TI - Growth hormone--a cogonadotropin? Its role in ovulation induction. PMID- 1919259 TI - Age and pregnancy rates in in vitro fertilization. AB - The influence of women's age on the results of in vitro fertilization (IVF) was analyzed in 1801 women undergoing the procedure. Advancing age was found to be related to significant reduced success rates from an average of 30.1% per transfer below the age of 36 years to 15.9% per transfer at 37 years or more (P less than 0.001). The decrease was related to a reduction in oocyte production (five at 25 years or less, four below the age of 40 years, three at 40 years or more, and two in the 43 to 47-year group) and probably due to reduced implantation. It is concluded that a woman's age must be considered an important prognostic factor when IVF is suggested. PMID- 1919258 TI - Serum and follicular fluid (FF) estradiol (E2) levels in ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) conception cycles after pituitary suppression. AB - Initial hope that ovarian hyperstimulation syndrome (OHSS) would be less likely to occur after pituitary suppression with gonadotropin releasing-hormone agonists (GnRH-a) has not been substantiated. GnRH-a/human menopausal gonadotropin (hMG) protocols often lead to OHSS with markedly elevated circulating estradiol (E2) levels in susceptible patients. This study was undertaken to determine whether or not intrafollicular E2 secretion is increased in these cases. Fifty-two in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) conception cycles treated with GnRH-a/hMG were included in the study. GnRH-a, leuprolide, 0.5 mg, was administered subcutaneously from day 20 of the preceding cycle and the ovaries were stimulated with hMG, 75-225 IU bid intramuscularly, followed by human chorionic gonadotropin (hCG), 5000 IU. Twenty cycles (Group I) were associated with moderate or severe OHSS and 32 cycles (Group II) did not result in OHSS. E2 was measured in the serum on the day of hCG (day 0), on the day of oocyte retrieval (day 2), and at midluteal phase (days 6-8), as well as in the follicular fluid (FF) using a solid-phase direct RIA. Mean serum E2 was significantly higher at all three sampling times in Group I (OHSS) than in Group II. Both the number of follicles and the number of oocytes were also significantly higher in Group I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919260 TI - The efficiency of cryopreserved semen versus fresh semen for in vitro fertilization/embryo transfer. AB - The efficiency of cryopreserved donor semen versus fresh donor semen in an in vitro fertilization/embryo transfer programme was evaluated. Thirty-nine in vitro fertilization/embryo transfer cycles were performed using fresh donor semen (group A) and 74 cycles were carried out using cryopreserved semen (group B). All patients underwent a uniform controlled ovarian hyperstimulation using high doses of human menopausal gonadotropins. Oocytes were retrieved transvaginally under ultrasound imaging. Semen (fresh or frozen-thawed) were prepared for insemination by a washing technique. Each ovum was inseminated with 500,000-600,000 motile spermatozoa. No significant difference was noted between the two groups regarding female age, duration of infertility, and number of ova retrieved per aspiration. Even though the fertilization rate in group B was significantly lower than in group A (55.5 +/- 3.8 vs 70.4 +/- 3.5, P = 0.008), pregnancy rates per embryo transfer were similar--39.3 and 38.5%, respectively. PMID- 1919261 TI - Abbreviated endometriosis-associated infertility correlates with in vitro fertilization success. AB - The utility of in vitro fertilization (IVF) for refractory infertility associated with endometriosis was studied by reviewing the 6-year experience with IVF and pregnancy follow-up at University Hospital, London, Ontario. Two hundred forty cycles were begun in 124 couples in whom endometriosis was the sole identified cause of infertility. In a program employing predominantly ultrasound-guided transvaginal oocyte retrieval, live birth rates were not reduced with advanced degrees of endometriosis. Live births were positively correlated with a shorter infertility duration. PMID- 1919262 TI - Hemizona assay: use of fresh versus salt-stored human oocytes to evaluate sperm binding potential to the zona pellucida. AB - The hemizona assay (HZA) has a high predictive value for in vitro fertilization (IVF) results. Oocyte quality plays a significant role in the validation of this test. The question was asked whether human salt-stored oocytes (up to 30 days) are damaged and subsequently lose their sperm binding capacity when compared to fresh human oocytes. Equivalent binding in both the salt-stored and the fresh group of oocytes was observed in the hemizonae incubated with normal semen as well as in their matching halves incubated with semen from an infertile man. Based on the results, we conclude that salt-stored oocytes (pH 7.0) give reliable information regarding sperm binding potential under HZA conditions. PMID- 1919263 TI - Fluid accumulation of the uterine cavity before embryo transfer: a possible hindrance for implantation. AB - Accumulation of fluid in the uterine cavity was recorded in three cases during vaginal ultrasound (US) monitoring for in vitro fertilization (IVF) cycles. The three patients had hydrosalpinges and tuboovarian cystic masses. They all had a common complaint of intermittent vaginal discharge. Attempts at aspirating the fluid to empty the cavity was done in two cases but the fluid recollected. This condition possibly renders the uterine cavity hostile to the transferred embryos and careful consideration should be taken to diagnose it. PMID- 1919265 TI - Use of in vitro fertilization and embryo transfer to circumvent infertility caused by an inherited imperforate vagina in mice. AB - An autosomal recessive mutation (ipv) causing infertility in homozygous females (ipv/ipv) because of imperforate vaginae was discovered in a line of mice selected for low lean tissue mass as a proportion of body weight. The aim of this study was to determine if the mutation could be propagated in offspring following embryo transfer of oocytes collected from mutant females and fertilized in vitro with sperm from males known to carry the gene (ipv/?). Caudal epididymal sperm were incubated with cumulus-enclosed oocytes for 8-10 hr in tissue culture medium 199 + 5% fetal calf serum + 0.4% bovine serum albumin. Oocytes possessing at least two pronuclei were transferred to recipient CD-1 females which had been mated 24 hr earlier to vasectomized males. A total of 683 oocytes was collected from 27 superovulated mutant females. A large proportion of the oocytes was abnormal as evidenced by cytoplasmic fragmentation (259/683, 38%). Seventy-eight percent (331/424) of the normal oocytes were fertilized and 181 of these were transferred to 10 recipients. Six of 10 recipients delivered 38 offspring (24 females, 14 males). Fifty-eight percent (14/24) of the female offspring displayed an imperforate vagina. The results demonstrate that in vitro fertilization and embryo transfer can be used for propagating a mutant gene that causes infertility in females. PMID- 1919264 TI - Protein kinase C activity and protein phosphorylation in mouse eggs. AB - The treatment of mouse eggs with phorbol esters and diacylglycerol inhibits sperm penetration and results in biochemical modification of the zona pellucida. In this report, we have demonstrated the presence of protein kinase C (PKC) activity in mouse eggs as determined by 12-O-tetradecanoyl phorbol-13-acetate (TPA) dependent in vivo and in vitro protein phosphorylation in mouse eggs. When mouse eggs were radiolabeled with [32P]phosphate and treated with TPA, two specific proteins, 70 and 20 kDa, were phosphorylated. The 70-kDa protein was also phosphorylated in vitro by endogenous PKC. In addition, we have shown that exogenous PKC induced the in vitro phosphorylation of 70-, 55-, and 20-kDa proteins in egg extract. The 70-kDa protein was also phosphorylated in vitro after treatment of the cytosol fraction of mouse eggs with TPA, suggesting that this protein might be a specific substrate for PKC and that it is located in the cytosol. These results demonstrate that mouse eggs contain PKC activity and suggest that PKC-catalyzed protein phosphorylation of specific proteins might be involved in the regulation of egg-induced modification of the zona pellucida. PMID- 1919266 TI - Comparison of luteal-phase support with high- and low-dose progesterone therapy on pregnancy rates in an in vitro fertilization program. PMID- 1919267 TI - Increased fertilization of human oocytes with low sperm density at insemination. PMID- 1919268 TI - Effect of topical prostaglandin PGA2, PGA2 isopropyl ester, and PGF2 alpha isopropyl ester on intraocular pressure in normotensive and glaucomatous canine eyes. AB - Topical instillations of 1.0, 10, and 20 micrograms/50 microliters of prostaglandin PGA2, 0.5 and 1.0 microgram/50 microliters of PGA2 isopropyl ester, and 0.5, 1.0, 5.0 and 10.0 micrograms/50 microliters of PGF2 alpha isopropyl ester were evaluated in the normal dogs and glaucomatous beagles eyes. Each concentration of drug was evaluated for a seven day period. On Day 1 baseline values were obtained, days 2-4, the drug was instilled (once a day) and on days 5 7 post-treatment values were measured. All concentrations of PGA2 failed to lower intraocular pressure (IOP) in the normal and the glaucomatous (P greater than 0.72) dogs. PGA2 isopropyl ester decreased IOP in the normal dogs and in the glaucomatous beagles (P less than 0.01). The declines in IOP were significant at 1/2 to 1 hour and continued for up to 5 hours. No significant change in IOP occurred in the non-treated fellow eye of the normotensive dog (P less than 0.54) and the glaucomatous beagle (P less than 0.29). All concentrations of PGF2 alpha isopropyl ester significantly decreased IOP in the treated eyes of the normotensive dog (P less than 0.05) and the glaucomatous beagle (P less than 0.01). The significant change in IOP occurred within one hour after the instillation of PGF2 alpha isopropyl ester. The IOP remained lower than the baseline pressures 24 hours post-treatment for both the normotensive and glaucomatous dogs. Maximal change in IOP for normal dogs was a decrease of 9 mm Hg while the glaucomatous beagle had a decrease of 19 mm Hg. No significant change in IOP occurred in the non-treated fellow eye of the normotensive animal (P less than 0.16) and the glaucomatous beagle (P less than 0.40). The side effects of PGF2 alpha isopropyl ester were miosis and mild conjunctival irritation. PMID- 1919269 TI - The effect of a glaucoma medication reminder cap on patient compliance and intraocular pressure. AB - A multi-site, open-labeled clinical trial was conducted to evaluate the ease of use and acceptance of a newly developed medication cap with a memory aid (C Cap Compliance Cap, Allergan, Inc.) and its effect on patient compliance and intraocular pressure. One-hundred-twenty-two patients with glaucoma or ocular hypertension received their prescribed eye drops in bottles with the compliance cap. Overall, 83% of the patients found the compliance cap very easy to use. By the end of the study, significantly more patients (67%) claimed 100% compliance than prior to using the compliance cap (41%). An overall drop in intraocular pressure of 0.8 mm Hg was seen. However, in a subset of patients who reported an increase in compliance, mean intraocular pressure decreased from baseline by 1.7 mm Hg. The results of this study suggest that the compliance cap helps patients with glaucoma or ocular hypertension remember to take their medication as prescribed. PMID- 1919271 TI - Quantitation of scleral tobramycin levels. AB - We have devised a new method to solubilize sclera in order to permit quantitative determination of tobramycin by commercially available and widely utilized means. The sclera, containing tobramycin, was digested with Alcalase (Subtilisn A, NOVO Enzymes) and the tobramycin level was quantitated by TDX autoflourophotometry. This technique is accurate and sensitive. The tissue digestion and antibiotic assay are relatively simple to perform and should be applicable to a variety of antibiotics and possibly other therapeutic agents. PMID- 1919270 TI - Accumulation of amino acids and hydroxyl free radicals in brain and retina of gerbil after transient ischemia. AB - The mongolian gerbil was introduced as a stroke model because of its incomplete circle of Willis. Unilateral carotid ligation ischemia produced in such a fashion was not effective in all gerbils. We have selected gerbils by examination of the ocular fundus to study the level of amino acids and hydroxyl free radicals (OH0 formation of DHBA, dihydroxybenzoic acid, from salicylate) in gerbil cerebral ischemia. Only gerbils with absence of retinal blood after ligation were selected as sensitive. One group (sham operated) served as control. The other group was subjected to unilateral left carotid occlusion with a clip during 30 minutes and classified as sensitive and non sensitive. Sixty minutes after release of the clip, levels of aspartate, glutamate, GABA were quantified in left hippocampus and in left retina. Levels of 2,5 DHBA (2,5 dihydroxybenzoic acid) were quantified in left retina and in left hemisphere. Compared to sham operated group, levels of aspartate (greater than 371%), glutamate (greater than 318%), GABA (greater than 122%) and 2,5 DHBA (greater than 385%) significantly increased in the group subjected to carotid occlusion. The determination of concentrations of amino acids and 2,5 DHBA in sensitive gerbils was a suitable method to study cerebral and retinal ischemia. PMID- 1919272 TI - Experimental transscleral iontophoresis of ciprofloxacin. AB - Ciprofloxacin was administered into the aqueous humor and vitreous body of the rabbit eye by transscleral iontophoresis. Positively and negatively charged forms of the drug molecule were tested. Therapeutic concentrations of ciprofloxacin were achieved in the aqueous body only when the negatively charged drug molecule was used. Ciprofloxacin did not reach the vitreous body in therapeutic concentrations in either the positively or negatively charged form, but higher concentrations were achieved when the drug was negatively charged. Peak levels were obtained in the aqueous and vitreous bodies (0.62 micrograms/ml and 0.19 micrograms/ml, respectively) one hour after transscleral iontophoresis of negatively charged ciprofloxacin at 5 mA for 15 minutes. PMID- 1919274 TI - Comparative corneal penetration of prednisolone sodium phosphate and prednisolone acetate in NZW rabbits. AB - Comparative corneal penetration studies in the literature with prednisolone sodium phosphate solution and prednisolone acetate suspension administered to rabbit eyes give conflicting results concerning the greater bioavailability of prednisolone acetate. A recent in vitro penetration study shows similar fluxes for both salt forms in terms of prednisolone, quantified by a specific HPLC assay. An in vivo comparison has been conducted in NZW rabbit eyes and shows similar bioavailability for both drugs. Prednisolone sodium phosphate, prednisolone acetate and the primary metabolite prednisolone are quantified by a specific HPLC assay in aqueous humor. PMID- 1919273 TI - Reduction of cat eye movements using retrobulbar botulinum toxin. AB - We studied the effects of a single retrobulbar injection of Botulinum toxin on the motility of cat eyes. Four cats were sedated and the opposite eye served as a control. Eye movements were plotted by reflecting a laser beam from a mirror fixed to the cornea. We found the mean degrees of deviation per eye per day and summarized these results as mean degrees of deviation per eye per week +/- standard deviation. Statistical analysis was accomplished using Student's t test for independent measures, since measurement of the treated eye pairs was done in a randomized manner on different test days. (table; see text) These results indicate that a single retrobulbar dose of Botulinum toxin can produce a paralysis of the ocular musculature lasting in excess of four weeks in a specific and reproducible manner. In addition, this methodology should prove useful in future experiments in which ocular motility might prove to be a technical concern. PMID- 1919275 TI - Systemic absorption of ocular timolol in poor and extensive metabolizers of debrisoquine. AB - The oxidation of timolol exhibits genetic polymorphism of debrisoquine type. After oral administration, poor metabolizers have high timolol concentrations in plasma and show an intensified systemic beta-blockade. Since the contribution of debrisoquine metabolizer status on timolol eyedrop therapy is not known we determined the systemic absorption of ocularly applied timolol in healthy subjects classified either extensive or poor metabolizers. Unlike after oral timolol ocular drug administration caused higher peak drug concentrations in plasma in extensive metabolizers. The variation in the systemic absorption of ocular timolol contributed more than the debrisoquine oxidation phenotype to timolol plasma levels after a single ocular timolol application. PMID- 1919276 TI - Absence of drug effects on rabbit blood-aqueous barrier permeability to non electrolytes. AB - The effects of either topical epinephrine, norepinephrine or pilocarpine upon the entry of non-transported radioactive solutes into the anterior or posterior chamber of pigmented rabbit eyes was examined after intravenous solute perfusion. Solutes employed were urea, thiourea, sucrose and inulin. They were infused at a rate that maintained constant plasma levels from 1 minute through 5 hours of intravenous perfusion. Anterior and posterior chamber samples were taken at either 5 minutes or 5 hours after infusion of solutes, but in either case at 1 hour after drug administration. Differences between the 5 minute and 5 hour data showed more solute entry with the passage of time, and differences were found between the rate of solute entry at both times based upon molecular size. However, while occasional statistically significant differences were found between certain drug treatments, no drug effects were noted on solute entry into the treated eye either when compared to the contralateral untreated eye or to a separate untreated control group. PMID- 1919277 TI - Microprocessor based detection of epileptic discharges. AB - Parametric and Non-parametric methods have been developed for the detection and interpretation of EEG data for normal and abnormal patients. These methods have been implemented on mainframe computers or dedicated microcomputers. The heuristic methods are suitable for implement on dedicated microprocessor based system as they involve less degree of computation in comparison to the parametric methods. In this work a microprocessor based system has been developed and heuristic pattern recognition technique has been applied, which is based on the measurement of amplitude, duration slopes etc. for the detection of spike and sharp waves as well as the different frequency band of background activity. The computed values of amplitude and durations are shown on the graphs from which the different symptoms based on EEG are determined. PMID- 1919278 TI - The use of a personal computer program for monitoring wound infections and other complications in orthopedics. AB - A personal computer program to monitor wound infections and other complications after orthopedic operations was developed, adopting international criteria and definitions. The program offers fixed data entry screens, and a free text editor, and produces user-specified variations of seven screen pages comprising most of the epidemiological data needed for surveillance and complication control. Furthermore a number of special lists can be generated for use in the daily work. For all reports and lists it is possible to generate subpopulations with up to twelve criteria. The program was tested in four danish orthopedic departments and serves well as a simple local tool for the operating staff, offering fast information on complication rates. Results consisting 2,583 operations are presented. The overall rates of complications were 1.8% superficial wound infections, 0.6% deep wound infections, 2.6% other infections and 3.8 other complications. The system is lowcost and an effective method of providing a widespread uniform surveillance of surgical wound infections and other complications in the orthopedic wards. PMID- 1919279 TI - Using a microcomputer to convert percent response values to probits. AB - Certain relationships between dose/concentration and percent response/binding in various biochemical systems are sigmoidal rather than linear. This sigmoid relationship is considered linear only over the 20-80 percent range. Appropriate analysis of such data over nearly the entire response/binding range requires the conversion of the percent response data to probits or probability units, producing a linear relationship. While tables of probits are available, the author has incorporated the probability function for probit conversion into a commercially available spreadsheet program. Also included is the Rohlf and Sokal approximation for the area under the normal distribution curve (conversion of probits to cumulative percent). These functions allow use of a spreadsheet to automate the creation of dose-response curves, or standard curves as part of chemical assays (i.e., radioimmunoassay). PMID- 1919280 TI - Expert control of the arterial blood pressure during surgery. AB - During and after many surgical procedures the patient's arterial blood pressure must be artificially decreased to a lower than normal level. Although there are alternatives, infusion of the drug sodium nitroprusside (SNP) is frequently the preferred technique to achieve this controlled hypotension. The fast action of the drug and the danger of a too low pressure make manual control of the SNP infusion flow rate, even if done by an expert, a difficult and demanding task. This is mainly due to an occasional large unpredictable variability over time of the patient's sensitivity to SNP, and to the fact that a multitude of other factors also influence the arterial pressure. Due to these and several other causes, current automatic controllers cannot handle all cases equally well. A new expert system based SNP controller was designed to perform well for all patients, regardless of their characteristics. It monitors and adjusts its own performance, employing a number of heuristics derived from a careful study of the properties of the arterial pressure signal, the effects of SNP and other clinical provocations on the arterial pressure, and the ways in which expert clinicians manually manage the SNP infusion. Expert systems technology allows the new controller to access and employ this type of expert medical knowledge, resulting in expert-level performance. The controller was tested on 30 patients undergoing cardiac surgery, both before, during and after bypass. It was safe, needed little attention, and performed well in all cases. PMID- 1919281 TI - Three dimensional closed loop control of the human circulation. AB - In the control of the circulation it is suggested there is merit in describing states which are the object of each therapy. Considering the determinants of venous return rather than those of cardiac output, we suggest that the mean systemic filling pressure is a parsimonious description of the volume state. A method is described of deriving a mean systemic filling pressure analogue based on stopping the flow in a notional regional systemic circulation. The mean systemic filling pressure (PM) forms a quantitative link between volume therapy and circulatory dynamics. The systemic vascular resistance is a conventional measure of the state of arteriolar resistance. We suggest that the ratio (PM - PRA)/PM (where PRA is the right atrial pressure) is a global measure of the effect of cardioactive drugs. Studies are reported in which the mean blood pressure, right atrial pressure and cardiac output are simultaneously controlled within desired tolerances using state based control. PMID- 1919282 TI - Medical logic module (MLM) representation of knowledge in a ventilator treatment advisory system. AB - In any medical expert system it is the inherent knowledge that is the power of the system and not the particulars of its implementation. Therefore it would be valuable to use a representation that would allow: knowledge transfer between different systems, users, experts and 'importers' to be able to evaluate the logic, experts to easily input their knowledge and be guided how to use the syntax. Adren Syntax of Medical Logic Module is a proposed knowledge representation, fulfilling these criteria. The Arden Syntax has been used to represent rules and logic in a decision support system for ventilator therapy in patients with acute respiratory failure (ARF) that is under development. The medical experts involved in the project have used the Arden Syntax as a convenient way for transfer and storage of medical knowledge. The syntax is easy to learn and may be used with a minimum of training. In the present system, Medical Logical Modules have been used to represent knowledge pertinent to the initiation and maintenance phases of ventilator therapy. PMID- 1919283 TI - NOTIS: an operating theatre information system. AB - Solutions to straightforward resource management problems need not always involve the use of complex, specialised and expensive software solutions. Commercially available 'off the shelf' packages have increased in flexibility and ease of use, and are usually an order of magnitude cheaper than their custom designed counterparts. In response to a request for a low cost database suitable to be used on a stand-alone microcomputer system, the widely available integrated software package Smart was used. The program specification required quantification and analysis of the workload in a medium sized operating theatre suite (at 6,000 cases/year) to be undertaken. In addition to providing Database, Spreadsheet and Wordprocessor modules, each with rapid and easy exchange of data from one module to another, Smart incorporates its own programming language. This may be used to build up complex series of instructions for data manipulation, to generate menus and create a naive user front end to the finished program. Although an adequate knowledge of database construction and basic programming are necessary, professional programming skills are not required. NOTIS, the Newham Operating Theatre Information System, is a menu driven program designed to be used by clerical staff, and accepting patient data derived from within the operating theatre. At the end of each month a set of predetermined reports are produced. These reports are designed to provide information on the workload, case type and medical personnel involvement applicable to theatre managers, anaesthetists and surgical staff. PMID- 1919284 TI - Automated real-time data acquisition and analysis of cardiorespiratory function. AB - Microcomputer generation of an automated record without complexity or operator intervention is desirable in many circumstances. We developed a microcomputer system specifically designed for simplified automated collection of cardiorespiratory data in research and clinical environments. We tested the system during possible extreme clinical conditions by comparison with a patient simulator. Ranges used were heart rate of 35-182 beats per minute, systemic blood pressures of 65-147 mmHg and venous blood pressures of 14-37 mmHg, all with superimposed respiratory variation of 0-24 mmHg. We also tested multiple electrocardiographic dysrhythmias. The results showed that there were no clinically relevant differences in vascular pressures, heart rate, and other variables between computer processed and simulator values. Manually and computer recorded physiological variables were compared to simulator values and the results show that computer values were more accurate. The system was used routinely in 21 animal research experiments over a 4 month period employing a total of 270 collection periods. The file system integrity was tested and found to be satisfactory, even during power failures. Unlike other data collection systems this one (1) requires little or no operator intervention and training, (2) has been rigorously tested for accuracy using a wide variety of extreme patient conditions, (3) has had computer derived values measured against a standardized reference, (4) is reliable against external sources of computer failure, and (5) has screen and printout presentations with quick and easily understandable formats. PMID- 1919285 TI - Nuchal cord: a definition and a study associating placental location and nuchal cord incidence. AB - The umbilical cord around the neck of the fetus at the time of birth has been referred to in the literature by many different terms, including the term nuchal cord. A standardized definition of nuchal cord is proposed in order to allow for more accurate study of this problem. A prospective study is undertaken applying this specific definition. The results suggest a statistically significant relationship between nuchal cord incidence and placental location. A relationship between fetal heart rate decelerations and placental location also surfaced. PMID- 1919286 TI - Percutaneous lumbar disc excision: experience with sixty cases and review of the literature. AB - A series of 60 cases of percutaneous disc excisions is presented. There were 43 males and 17 females with an average age of 36 years. All cases were failures of conservative treatment and were disabled for their usual occupation. Results were excellent or good in 44 cases, satisfactory in four and failures in eight. There was no postoperative complication. The importance of a complete radiologic workup is emphasized. The cost/benefit and risk/benefit ratios of this operation compare favorably with conventional open laminectomy. The procedure is best indicated in younger patients with good distal water content and contained herniated lumbar disc. It is contraindicated in patients with a free fragment and in patients with previous surgery at the same level. PMID- 1919287 TI - EKG of the month. Concatenations of the heart. Atrial flutter. PMID- 1919288 TI - 526 spinal cord injuries: experience of the Louisiana Rehabilitation Institute, 1965-1984. AB - A retrospective chart review was carried out on all spinal cord injured patients admitted to the Louisiana Rehabilitation Institute, Charity Hospital, between 1965 and 1984. In addition, former patients who could be contacted and who gave their informal consent were interviewed by telephone about the circumstances of their injury. The patients were most commonly male (86%) and black (53%); the average age at injury was 29, the most common diagnosis was complete paraplegia (44%); and the leading cause of injury was gunshot (or other penetrating) wounds (41%) followed by motor vehicle crashes (36%). These findings mirror the pattern of serious injury in Orleans Parish as a whole and point to firearms as a major health hazard in this community. PMID- 1919289 TI - The effect of underlying philosophy upon utilization of a program for impaired medical students. AB - In recent years, an increasing number of medical schools have implemented educational programs for their impaired, or potentially impaired, students. The present research analyzed one such program viewing it as an organizational innovation and employing a theoretical model from the organizational literature. A survey sample of 170 medical students representing all four classes and recently graduated interns was utilized. Subjects were queried as to anticipated program use, degree of exposure to the program, accuracy of knowledge of the program, and perceived program advocacy. Via ANOVA analysis (regression approach) it was found that the general advocacy stance of the medical school toward the innovation (general diffusion emphasis) was not an influential factor upon potential use of the program by medical students. However, its concentration upon the actual procedures to be employed (specific diffusion emphasis) was a much better predictor. The implications for such a finding on the structure of future kindred educational programs was discussed. PMID- 1919290 TI - Malignant hyperthermia: case report and literature review. PMID- 1919291 TI - Bacterial osmoprotection. PMID- 1919292 TI - Inflammatory cells and the hypermetabolism of head injury. PMID- 1919293 TI - Immunopathogenesis of Pneumocystis carinii infection. PMID- 1919294 TI - Effect of NaCl-induced osmotic stress on intracellular concentrations of glycine betaine and potassium in Escherichia coli, Enterococcus faecalis, and staphylococci. AB - Staphylococci are more salt tolerant than are enterococci or Escherichia coli. They have a more rigid cell wall and higher internal turgor pressure. The mechanisms of NaCl-induced osmotic tolerance among these bacteria were examined by determining the generation of osmoprotective activity of cellular extracts and intracellular concentrations of glycine betaine and potassium (K+) in response to graded amounts of NaCl. Staphylococci as well as E. coli were shown to require choline or glycine betaine to achieve maximal salt tolerance. In response to 0.9 mol/L NaCl, E. coli exhibited a marked increase in osmoprotective activity, a 168 fold rise in glycine betaine, and a 2.3-fold rise in K+. Enterococcus faealis exhibited a small increase in osmoprotective activity, a 9.3-fold increase in glycine betaine, and a twofold increase in K+. In contrast, strains of Staphylococcus aureus, S. epidermidis, and S. saprophyticus were found to have considerably greater osmoprotective activity, glycine betaine, and K+ than other organisms, even in the absence of external osmotic stress. Glycine betaine rose in some strains, but K+ remained virtually unchanged as the concentration of NaCl was increased. The high concentrations of glycine betaine and K+ in staphylococci, even in the absence of osmotic stress, may explain in part their remarkable salt tolerance and high turgor pressure. PMID- 1919295 TI - Increased plasma and ventricular fluid interleukin-6 levels in patients with head injury. AB - The cytokine interleukin-6 (IL-6) plays a major role in initiating the acute phase response, especially in the production of acute phase reactants such as C reactive protein. The objectives of this study were to determine whether plasma or ventricular fluid IL-6 levels were elevated at time of admission after head injury and whether plasma IL-6 levels related temporally to clinical improvement of levels of acute phase reactants. Thirty patients with Glasgow Coma Scale (GCS) scores of 3 through 10 were observed for 15 days after head injury. Peak elevation of plasma IL-6 occurred on admission (85 +/- 12 U/ml; normal level is less than 2 U/ml) and then decreased during the hospital course to a level of 29 +/- 4 U/ml on day 15. Plasma IL-6 levels decreased significantly faster in patients with admission peak 24-hour GCS scores of 8 through 10 compared with patients with GCS score less than 8 (p less than 0.01). Patients had markedly elevated and variable ventricular fluid IL-6 levels on admission (mean 3880 +/- 2022 U/ml; normal, less than 2 U/ml). A temporal relationship was found between plasma IL-6 levels and multiple acute phase reactants thought to be mediated by IL-6. We conclude that plasma and ventricular fluid levels of IL-6 are elevated after head injury and that plasma IL-6 level is temporally related to acute phase reactants and clinical improvement. We suggest that IL-6 may play an etiologic role in many of the metabolic or nutritional sequelae of head injury. PMID- 1919296 TI - Antibodies in patients with recurrent respiratory papillomatosis treated with lymphoblastoid interferon. AB - Serum specimens from 53 evaluable patients enrolled in a clinical trial of lymphoblastoid interferon in recurrent respiratory papillomatosis were screened for the presence of interferon-binding antibodies by an indirect enzyme immunoassay and evaluated for neutralizing antibody measured as the inhibition of antiviral activity. Immunoglobulin G antibodies that specifically bound lymphoblastoid interferon were detected in 66% (35 of 53) of patients; neutralizing antibody was detected in 11 of the 35 patients having binding antibody (and in none of the patients who were negative for binding antibody). The incidence of detectable neutralizing antibody in this study population was 20.8% (11 of 53), which is markedly higher than in previous reports of lymphoblastoid interferon in patients with other diseases (i.e., less than 1% incidence). The cumulative dose received at the time of detection of neutralizing antibody ranged from 163 to 385 MU per square meter of body surface. Neutralizing antibody was detectable at a median time of 120 days after initiation of interferon therapy, and binding antibody appeared earlier in those patients (median 59 days) than in patients in whom only binding antibody was produced (median 116 days). Despite the tendency of binding antibody to appear either in patients in whom neutralizing antibody was eventually formed, the detection of binding antibody was not necessarily predictive of the subsequent development of neutralizing antibodies. Binding antibody persisted after neutralizing antibodies had become undetectable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919297 TI - Serum uric acid and its relation to cardiovascular disease risk factors in children and young adults from a biracial community: the Bogalusa Heart Study. AB - The distribution of serum uric acid and its relationship with cardiovascular risk variables have been studied in 3983 children and young adults, aged 5 to 26 years, drawn from a biracial (black and white) population. For two age groups, 5 to 11 years and 19 to 26 years, white subjects had significantly higher uric acid levels than black subjects, (4.02 mg/dl vs 3.57 mg/dl, p less than 0.0001, and 5.50 mg/dl vs 5.18 mg/dl, p less than 0.0001, respectively). Men in the 19 to 26 years age group had a significantly higher uric acid level than women (6.49 mg/dl vs 4.20 mg/dl, p less than 0.0001). White children and young adults were twice as likely to have levels above clinical limits than blacks, and males more likely to have hyperuricemia than females. Parents with a history of myocardial infarction were more likely to have children with hyperuricemia. Children and young adults with hyperuricemia had significantly higher plasma glucose (p less than 0.01) and insulin (p less than 0.001) levels, total cholesterol level (p less than 0.05), and serum triglyceride (p less than 0.0001), very-low-density lipoprotein cholesterol (p less than 0.01), low-density lipoprotein cholesterol (p less than 0.001), and total protein (p less than 0.0001) levels than subjects without hyperuricemia; high-density lipoprotein cholesterol level was significantly lower (p less than 0.0001) in subjects with hyperuricemia than in those without it.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919298 TI - A heparin-like anticoagulant as part of global abnormalities of plasma glycosaminoglycans in a patient with transitional cell carcinoma. AB - A patient is described in whom a circulating heparin-like anticoagulant developed during the terminal course of metastatic transitional cell carcinoma. The anticoagulant, which was identified as heparan sulfate, was the clinical sign of global abnormalities in the patient's plasma glycosaminoglycans. Subsequent analysis disclosed increased amounts of chondroitin sulfate as well as heparan sulfate. In addition, the charge density and molecular weight of the patient glycosaminoglycans and their organization into proteoglycans differed significantly from glycosaminoglycans isolated from normal plasma samples. PMID- 1919299 TI - The effects of temporary occlusion of the superior mesenteric vein or splenic vein on biliary bilirubin and bile acid excretion in rats. AB - To elucidate the possible implication of hepatic blood supply to the occurrence of hepatolithiasis, the rat superior mesenteric vein, which drains blood from the intestine, or the splenic vein, which drains from the spleen, was occluded for 30 minutes. Changes in the hepatic oxygen saturation index, intrahepatic uridine diphosphate-glucuronic acid concentration, bile flow, and the excretion of bilirubin as well as its fraction, along with bile acid in bile before and after the procedure, were observed. In association with superior mesenteric vein occlusion, oxygen saturation index, hepatic uridine diphosphate-glucuronic acid concentration, bile flow, bile acid concentration in bile, and percentage of biliary bilirubin diglucuronide were all decreased. Incubation of bile under sterile conditions from rats with occluded superior mesenteric veins resulted in precipitation of mainly calcium salt of fatty acid. In contrast, splenic vein occlusion caused no changes except for a decrease in biliary bilirubin concentration. Incubation of bile from rats with occluded splenic veins did not induce precipitation. From these findings it can be concluded that blood flow in the superior mesenteric vein is the primary source of oxygen supply to the rat liver and that this vein plays an important role in maintaining bile flow, bile acid excretion, and bilirubin conjugation and in preventing the precipitation of bile (possibly preventing hepatolithiasis). PMID- 1919300 TI - Effects of the oral anticoagulant phenprocoumon on blood coagulation and thrombogenesis induced by rabbit aorta subendothelium exposed to flowing human blood: role of dose and shear rate. AB - We investigated the effect of oral anticoagulation on thrombogenesis induced by the subendothelium of rabbit aorta. Eighteen healthy volunteers underwent a 2 week treatment with the oral coumarin preparation phenprocoumon to a target international normalized ratio (INR) of 5. By using an ex-vivo perfusion chamber system, the interaction between flowing blood and exposed subendothelium was measured at low (50 sec-1) and high (650 sec-1) wall shear rates. The low shear rate simulated blood flow in venous vessels and the high shear rate simulated blood flow in arterial vessels. Deposition of fibrin, platelets, and platelet thrombi on subendothelium was quantified by morphometric and immunologic techniques. Fibrin deposition prevailed at the low shear rate (183 +/- 57 ng/mm2 vs 46 +/- 16 ng/mm2, low vs high shear rate; mean +/- SEM; p less than 0.01). In contrast, the interaction of platelets with subendothelium was more intense at high shear rates when compared with low shear rates, as indicated by higher platelet adhesion (44% +/- 2% vs 9% +/- 1% coverage of subendothelium with platelets, p less than 0.001) and platelet thrombus volumes (3.6 +/- 0.4 microns 3/microns 2 vs 1.3 +/- 0.3 microns 3/microns 2, p less than 0.001). Fibrin deposition on subendothelium was substantially reduced even at a low intensity of anticoagulation (reduction by 60% at INR 2.1 and by 75% at INR 3.7) and was abolished after high coumarin doses (INR 5.2). In contrast, a significant inhibition of platelet thrombus formation could be achieved only by high doses of phenprocoumon (INR 5.2). Our data indicate that relatively low doses of oral anticoagulants (INR between 2 and 3.5) substantially inhibit the fibrin formation on subendothelium prevailing at venous shear conditions, whereas a high intensity of anticoagulation (INR 4 to 5) is necessary to inhibit the formation of platelet rich thrombi prevailing at arterial shear conditions. PMID- 1919301 TI - Iron-restricted erythropoiesis as a limitation to autologous blood donation in the erythropoietin-stimulated bone marrow. AB - Recombinant human erythropoietin has been demonstrated to significantly increase autologous blood procurement. To determine the importance of dietary or prescribed iron absorption, we analyzed iron-restricted erythropoiesis in this setting. No differences were found when premenopausal placebo and erythropoietin treatment groups were compared for hematocrit changes, number of units donated, percentage of phlebotomies deferred, and total blood volume procured. Seven of 10 women who had not reached menopause donated more blood iron than the apparent amount of total mobilizable iron available, demonstrating that dietary or prescribed iron had to be absorbed to donate the amount of blood iron stored. Thus oral iron absorption can potentially be a limitation to erythropoiesis in the presence of erythropoiesis therapy in women who have not reached menopause. In contrast, none of 16 women who had reached menopause and only two of 21 men required oral absorption of dietary or prescribed iron for the amount of blood iron donated. We conclude that although oral iron supplementation may not be necessary in men and in women who have reached menopause, alternatives to oral ferrous salt supplementation could be tested to determine whether such alternatives would improve the response to erythropoiesis in premenopausal women. PMID- 1919302 TI - Harvey Cushing's circus friend, the "world's ugliest woman". PMID- 1919303 TI - Prosecution or persecution? PMID- 1919304 TI - Fraud and abuse liability in the health care profession. PMID- 1919305 TI - Epidural morphine pruritus reduction with hydroxyzine in parturients. AB - A majority of patients experience pruritus, nausea and/or emesis following epidural morphine administration post-cesarean section. Naloxone or diphenhydramine are commonly used to treat these side effects. Prevention or reduction in the incidence of side effects of epidural morphine is a clinical goal. The purpose of the study was to observe the efficacy of prophylactic administration of hydroxyzine on the incidence and severity of pruritus following the epidural administration of morphine in 40 patients who requested epidural morphine for postoperative pain relief. Group I (n = 20) received saline, while Group II (n = 20) received 50 mg of hydroxyzine ten minutes after the administration of 5 mg epidural morphine. Both solutions were administered by deep intramuscular injection in the thigh area. The results of this investigation demonstrated that hydroxyzine was efficacious in attenuating the incidence of severe pruritus. PMID- 1919307 TI - Familial cardiac amyloidosis. Diagnosis by immunocytochemistry. AB - Familial cardiac amyloidosis is a rare disorder that is difficult to diagnose. There is no specific therapy for this disease, but it is important to distinguish the cardiac and gastrointestinal symptoms of this disease from those of other treatable causes. We have treated a patient with this disorder who presented with cardiac and gastrointestinal symptoms. The diagnosis of amyloidosis was suspected on rectal biopsy and was confirmed by immunocytochemistry and immunoalkaline phosphatase technique. Pre-albumin was demonstrated in the lesion. We concluded that when familial amyloidosis is suspected, a biopsy from the suspected organ system is helpful for the diagnosis. The detection of pre-albumin by immunocytochemistry can elucidate the diagnosis of familial amyloidosis. PMID- 1919306 TI - Bronchogenic carcinoma and the acquired immunodeficiency syndrome. AB - The majority of patients with the acquired immunodeficiency syndrome will develop clinical and radiographic pulmonary involvement during the course of their disease. Although opportunistic pathogens account for the majority of these intrathoracic abnormalities, pulmonary neoplasms are being encountered more often than would be expected for the age group under consideration. Clinicians need to be vigilant for the possibility of the early appearance of bronchogenic carcinoma in this subset of patients. PMID- 1919308 TI - A message to surgeons. PMID- 1919309 TI - A response to Dr Nelson. PMID- 1919310 TI - The implementation of audit in an ENT unit. AB - ENT Departments in the United Kingdom are faced with increasing pressure from government, management and the Colleges responsible for surgical training to introduce formal medical self audit. The plethora of guidelines and publications on the subject rarely address the differences in clinical practice between general medicine or surgery and that of otolaryngology. Clearly the lead in the introduction of medical audit will come from the appropriate specialist associations; however, this paper aims to share the experience of the implementation of audit in one otolaryngology, head and neck surgery unit and offer suggestions for a programme elsewhere. PMID- 1919311 TI - Development of tympanosclerosis in children with otitis media with effusion and ventilation tubes. AB - Ventilation tube (VT) insertion is an accepted treatment for chronic otitis media with effusion (OME) in children. One hundred and eighty five children with bilateral OME were treated by unilateral myringotomy and VT insertion with no treatment to the contralateral ear. During a 5 year follow-up 95 of the children required only one VT but the remainer required more than one but always treatment was carried out to the same ear. The rate of development of tympanosclerosis was measured and scored. After 2-3 years the extent of the sclerotic changes stabilised and the rate of development reached 37-39 per cent in ears receiving only one VT, compared with 47-49 per cent in ears treated by more than one tube. The extent of the changes was no different whether or not one or more than one tube had been inserted. There was no overall evidence of resolution of sclerotic change with time. PMID- 1919312 TI - Prognostic significance of hearing loss as a lateralizing indicator in the surgical treatment of vertigo. AB - In patients with peripheral vertigo the presence of an asymmetrical hearing loss is an important lateralizing sign, having both diagnostic and prognostic significance. In a consecutive series of 83 patients undergoing retro labyrinthine vestibular nerve section for uncontrolled vertigo, asymmetrical hearing loss was associated with an 83 per cent incidence of complete control of vertigo and a 49 per cent incidence of complete relief from dysequilibrium. In the absence of a lateralizing hearing loss, the figures were 50 per cent and 24 per cent respectively (p less than 0.01 and p less than 0.05). The explanation for this finding may be that the presence of a hearing loss is more often associated with an exclusively peripheral disorder (controllable by peripheral surgical ablation), whereas in patients with symmetrical hearing there may be an unrecognized central or contralateral pathology resulting in less effective results from a unilateral peripheral surgical approach. The bithermal caloric test did not give such useful diagnostic or prognostic information. PMID- 1919314 TI - Bilateral facial nerve palsies: Groote Schuur Hospital experience. AB - Bilateral facial nerve palsies are rare. This article details the Cape Town experience of 24 patients with this condition seen over the past 20 years and highlights the three main groups in which these bilateral facial nerve palsies occurred. These are Bell's palsy, fracture of the temporal bones and sclerosteosis. A variety of other rare causes was also found. Bell's palsy remains a diagnosis of exclusion though there has been some evidence to suggest implication of the Herpes simplex virus. The mechanism whereby temporal bone fractures cause bilateral facial nerve palsies is discussed. The clinical presentation and management of sclerosteosis is also discussed. PMID- 1919313 TI - Pathology of labyrinthine ossification. AB - Ossification of the inner ear is the result of multifactorial pathogeneses, such as infection or malignant infiltration, and otosclerosis. Ossification of the inner ear spaces is a well documented sequela of suppurative labyrinthitis. In this study of human temporal bones, sections from 14 patients (28 temporal bones) were studied. In addition to the osseous tissue within the inner ear, findings included neoplasms, otosclerosis, otitis media, trauma, and Fabry's disease. We have attempted to correlate these conditions and their influence on the formation of osseous tissue within the spaces of the inner ear. Tympanogenic infection and vascular compromise were found to play an important role in ossification. The scala tympani of the basal turn of the cochlea was frequently the site involved. PMID- 1919315 TI - Subtraction magnetic resonance for tumours of the skull base and sinuses: a new imaging technique. AB - A new imaging technique is described, in which photographic subtraction as practised in angiography, is combined with Gadolinium enhanced Magnetic Resonance (GdMR) imaging and applied to the investigation of the paranasal sinuses and skull base. The densities on the subtraction image are dependent upon the blood supply of the tissues examined, thus producing a record of their vascularity: in effect a vasculogram. The method has proved to be technically feasible, and is advantageous in certain situations, particularly those in which the anatomy is complex as in the skull base or where normal structures have been distorted by previous surgery. The technique provides a more accurate record of tumour extent than that shown on unsubtracted GdMR scans. PMID- 1919316 TI - Transnasal sinusectomy with combined microscopic and endoscopic technique. AB - Severe, diffuse polyposis can be adequately treated through a transnasal approach which combines microscopic and endoscopic surgery. The operating microscope is used to perform ethmoidectomy, usually from the front to the back, and to open the sphenoid sinus and the antral window. The telescopes allow the sphenoid and maxillary sinuses to be cleaned under direct view control as well as enabling good drainage to be performed from the frontal sinuses. The results from 22 consecutive patients were good, with a very low rate of minor post-operative complications. PMID- 1919317 TI - Prospective study of the use of vasoconstrictor and saline in septal surgery for infiltration. AB - Vasoconstrictor agents are often used to reduce bleeding and hence improve the operative field in surgery. These agents are potentially dangerous. A trial was undertaken to compare the use of adrenaline 1:80,000 with saline alone as an infiltrating agent in 30 consecutive patients undergoing septoplasty under general anaesthesia. This study, based on a small number of patients can draw no firm conclusions. There are no really dramatic differences between 1:80,000 adrenaline and saline, in terms of blood loss, operative time and the condition of the operative field between the two groups. However, there is a possibility that there are substantial differences which, because of the variability of these outcomes, could not be detected in a study as small as this. It is recommended that a randomized trial involving patients is used to answer the question. PMID- 1919319 TI - Khat and oral cancer. AB - Oral cancers in the Asir region of Saudi Arabia have been observed to occur mostly among patients who have been long-term khat users. In a survey that reviewed cancers for the past two years there were 28 head and neck cancer patients, 10 of whom presented with a history of having chewed khat. One of these was a case of metastatic cervical lymph node and unknown primary, one was a parotid tumour, and the remaining eight presented with oral cancers. All were non smoking khat chewers and all of them had used it over a period of 25 years or longer. We conclude that this strong correlation between khat chewing and oral cancer warrants attention. PMID- 1919318 TI - Carcinoma of the lip: observations on its frequency in females. AB - Seventy-three patients with lip carcinoma were treated from 1970 to 1988 in the Otolaryngology Department of the Beilinson Medical Center. The most common histological type was squamous cell carcinoma which occurred in 68 patients; four tumours were basal cell carcinoma and one acinic cell carcinoma. Carcinoma of the lip is more frequent in males. Nevertheless, the frequency of carcinoma in females in our series was substantially higher than the average reported in the literature. Forty-nine patients were treated surgically and 24 patients were treated by irradiation. Analysis of the results among those treated by surgery and those treated by irradiation shows a difference in tumour local control which was statistically significant (p = 0.025). Surgical treatment is recommended because of the advantage of tumour margin assessment, avoidance of radiotherapy complications and rapid rehabilitation. Two rare cases of carcinoma of the lip in young patients (age under 20 years) are presented. PMID- 1919320 TI - Laryngeal morphology in sudden unexpected death in infants. AB - One hundred and four larynges removed from infants registered as dying from Sudden Infant Death Syndrome (SIDS) and 20 control larynges from infants of matching ages, were examined histologically. Excessive amounts of subglottic submucosal glandular tissue had reduced the available airway by more than half in 35 per cent of the SIDS larynges within the age group two of four months. In 30 per cent of this group the airway reduction was more than 60 percent. It is suggested that hyperplasia of subglottic mucous glands is one cause of fatal hypoxia in sudden unexpected infant death. PMID- 1919321 TI - Distribution of ear drops using a non-aerosol spray delivery system. AB - The distribution of ear drops in normal ears is variable. A new product Otomize (Stafford-Miller) containing dexamethasone and neomycin has a non-aerosol spray mist delivery system. This has been applied to normal ears and found to be superior in its distribution to generally available ear drops previously assessed. PMID- 1919322 TI - Sudden total deafness in sickle cell disease. AB - Sickle cell disease is a world-wide problem which has been noted to cause high tone sensorineural hearing loss. We report a case with sudden onset bilateral hearing loss which progressed to total sensorineural deafness. To our knowledge there has been no report of such a case occurring previously. PMID- 1919323 TI - Cochlear fistula found in a naturally healed tympanic cavity. AB - A cochlear fistula found in a naturally healed mastoid cavity is reported. The patient is a 53-year-old Japanese woman who was complaining of unsteadiness. She had a long history of otorrhoea in childhood. Her tympanic and mastoid cavities were widely open and were covered by thin epithelium. The posterior wall of the ear canal was missing. She had no hearing in the ear but responded to electrical promontory testing. Exploratory surgery was indicated at which fistulae of the basal turn of the cochlea and the horizontal semicircular canal were found. These fistulae were sealed by pieces of bone and muscle. PMID- 1919324 TI - Intralabyrinthine schwannoma. AB - Intralabyrinthine schwannomas are rare tumours which present with symptoms similar to Meniere's disease. Preoperative diagnosis is rarely possible and most are found incidentally during labyrinthectomy for persistent vertigo. A further case of this tumour is reported together with a review of the literature. PMID- 1919325 TI - Craniofacial fibrous dysplasia. AB - Fibrous dysplasia is a benign localized bone disorder of unknown aetiology in which endocrinopathies, abnormal pigmentation of the skin and mucous membranes may form part of the disease. Five cases involving the facial and cranial bones are described to illustrate the various presentations and radiological appearances including computerized tomography and magnetic resonance imaging. Some of these cases demonstrate that serial radiology may be adequate for diagnosis and management without the necessity for histological confirmation. The place of limited surgical treatment for the craniofacial sites is debated. PMID- 1919326 TI - Plunging ranula following bilateral submandibular duct transposition. AB - Submandibular duct transposition is now a standard surgical procedure for the treatment of severe drooling. However, this is our first experience of a plunging ranula arising as a complication of the technique. In the surgical management of this complication, the single most important step is excision of the sublingual gland to prevent recurrence. PMID- 1919327 TI - Nasal cartilaginous tumour. AB - A cartilaginous tumour of nasal region in a 6-year-old child is described. The problems of histological interpretation and treatment are discussed. PMID- 1919328 TI - Air cyst of the maxillary sinus (pneumosinus dilatans, pneumocoele). AB - A cystic dilatation of a paranasal sinus by an entrapped air mass has been termed pneumosinus dilatans or a pneumocoele. The occurrence of this condition in the maxillary sinus is quite rare. In the present case, a mid-face mass mimicking an osteoma was the presenting sign of the disease. The pathogenesis, clinical features and radiological aspects of this entity are reviewed. In order to avoid confusion with other conditions of different aetiopathogenesis, we propose to label the lesion as 'air cyst' of the paranasal sinus, a term that best describes the nature of the lesion. PMID- 1919329 TI - Extraskeletal myxoid chondrosarcoma of the maxillary sinus. AB - A case of extraskeletal myxoid chondrosarcoma of the maxillary sinus in a 45-year old man is reported and discussed. This is the first report of this tumour in this site. PMID- 1919331 TI - Inhalation of dental plates--a hazard of radiolucent materials. AB - Many dental plates are made of materials that are radiolucent. If inhaled or swallowed they may be difficult to detect and where there is strong suspicion of inhalation, early bronchoscopy should be carried out even if plain X-rays show no abnormality. The details of three patients are reported. PMID- 1919330 TI - Adenosquamous carcinoma of the hypopharynx. AB - A rare case of adenosquamous carcinoma of the hypophraynx is presented. The importance of primary surgical treatment is emphasised. PMID- 1919332 TI - Medullary (thyroid) carcinoma-like carcinoids of the larynx. AB - The histopathological spectrum of neuroendocrine neoplasms of the larynx includes a subset that may be indistinguishable from a medullary carcinoma of the thyroid gland. For a patient who presents with a medullary carcinoma-like metastasis in a cervical lymph node and in whom there is no clinically demonstrable thyroid lesion, a laryngeal atypical carcinoid must be excluded. The literature's third example of a primary medullary carcinoma-like atypical carcinoid of the larynx is presented. PMID- 1919333 TI - Primary extramedullary plasmacytoma of the salivary glands. AB - Primary extramedullary plasmacytomas (PEMP) are uncommon plasma cell neoplasms that generally occur in the submucosal tissue of the upper airway. Salivary gland PEMP is an extremely rare condition. This report describes a unique case of PEMP in the parotid gland associated with pulmonary amyloidosis. A review of all salivary gland PEMP's suggests that they behave similarly to PEMP's in other locations. The treatment of choice for localized disease is radiotherapy which should include regional lymphatics. Local control can be achieved in the majority of cases. The minority of patients develop systemic metastases and die from their disease. Chemotherapy can control disseminated disease and may induce remission. PMID- 1919334 TI - CT and MR imaging in lateral sinus thrombosis. AB - Establishing a pre-operative diagnosis of lateral sinus thrombosis can be difficult, as the clinical features are non-specific and laboratory tests unhelpful. CT may demonstrate abnormal high density of the lumen of the sinus, which does not enhance after intravenous contrast medium. Enhancement of the dura surrounding the sinus may be prominent, causing the 'empty triangle' or 'delta sign' which may suggest the diagnosis. Magnetic resonance (MR) imaging may show both lack of flow and abnormal signal from the sinus, thus providing definitive evidence of thrombosis. PMID- 1919335 TI - Verrucous carcinoma of the maxillary antrum. AB - Verrucous carcinoma is a rare variant of squamous cell carcinoma which occurs most frequently in the oral cavity and larynx. In this article we describe a patient with verrucous carcinoma of the maxillary antrum, and present a review of the literature. PMID- 1919336 TI - Glycoconjugates in the human fetal endolymphatic sac as detected by lectins. AB - The distribution of glycoconjugates in the 11 to 16 weeks old human fetal endolymphatic sac (ES) was analyzed using six biotinylated lectins; Wheat germ agglutinin (WGA), Abrus precatorius agglutinin (APA), Ulex europaeus agglutinin I (UEA-I), Ricinus communis agglutinin 120 (RCA120), Helix pomatia agglutinin (HPA), Concanavalin A (ConA). In the 11 week old human fetus, fluorescent reactions with WGA, APA, RCA120 and ConA were detected in the ES. There was almost no reaction with HPA and UEA-I. In the 14 week old human fetus, however fluorescent reactions with HPA and UEA-I appeared. This result suggests that the presence of glycoconjugates changes during the maturation process of the ES. Glycoconjugates detected with HPA were related to the epithelial cell elements of the ES epithelium. The reaction with UEA-I suggests that the stainable substance present in the ES lumen may be secreted locally by the ES itself. PMID- 1919337 TI - A correlative manometric and endoscopic study of tubal function in dry central perforation of the tympanic membrane. AB - Since good ventilation of the middle ear is a pre-requisite for successful myringoplasty, it was our policy to investigate the tubal function in dry central perforation of the eardrum and to correlate the manometric and endoscopic findings. Nasal endoscopy proved to be indispensable in diagnosing mechanical tubal obstruction and in localizing and even treating 'hidden' lesions in key areas, with probable normalization of the tubal function. The correction of the mechanical tubal obstruction must precede ear surgery. Whenever tubal obstruction is diagnosed as functional or idiopathic, the ventilation of the middle ear should be guaranteed during ear surgery by addition of a tympanostomy tube to the graft or drum remnant, and a guarded prognosis given. PMID- 1919338 TI - The deep oval window. AB - This article presents the results of an analysis of the variable and surgically important relationship between the oval window, the fossular walls and the related posterior tympanic recesses in 50 temporal bones. The visual impressions of superficial and deep oval windows seem to correspond fairly closely to the depth of the inferior wall of the fossula fenestra vestibuli (FFV). The depth of the superior and anterior walls of the FFV by themselves, did not appear to have such a dominating relationship in determining the deep oval window. There does not appear to be a well defined posterior wall in the vast majority of the specimens (86 per cent). In the event of scar tissue forming between the superior, inferior and anterior walls, the gap between the postero-superior part of the promontory and the posterior tympanic wall (posterior communication) could allow aeration of the region of the deep oval window in such an instance. Closure of this gap by a solid shelf of ponticulus or scar tissue could cause a localized malaeration of the fossula in most cases of deep oval windows. This is an entirely new concept of the likely problems of malaeration of a deep oval window which could arise due to anatomical variations and of the possible safety valve mechanism which could prevent such malaeration and its consequences. PMID- 1919339 TI - The fate of bone grafts in deep oval windows. AB - The use of bone grafts for total ossicular chain reconstructions in patients with deep oval windows may result in varying degrees of absorption of the segment of the bone graft in the fossula fenestra vestibuli. The mechanism of bone absorption is described--a condition not described before. PMID- 1919340 TI - Promontory stimulation following labyrinthectomy. AB - Promontory stimulation testing was carried out on a series of ten patients who had undergone osseous labyrinthectomy. The thresholds, discomfort levels and dynamic ranges were found to be comparable with a series of ten patients who have subsequently been successfully implanted with the Nucleus 22 channel cochlear implant. These findings suggest that cochlear implantation might be possible in a labyrinthectomized ear. PMID- 1919341 TI - Measurement of drill-generated noise levels during ear surgery. AB - The results of intraoperative monitoring of the electrocochleogram in patients undergoing surgery for poorly controlled Menieres Disease are presented with particular reference to the masking effect of drill-generated noise. The results obtained using a direct, in vivo, electrophysiological method of assessment of drill-generated noise levels are compared with previous postmortem and intraoperative studies and the implications with respect to the likelihood of drill-generated noise induced acoustic trauma are discussed. PMID- 1919342 TI - Mast cell numbers in the mucosa of the inferior turbinate in patients with perennial allergic rhinitis: a light microscopic study. AB - The number of mast cells in the inferior turbinate from patients with perennial allergy due to house dust mite were compared with ten normal controls. Ten random high powered fields were counted in the epithelium and the submucosa in samples which had been divided into two and fixed either in aqueous formalin or Carnoy's fixative. The sections from each block were stained with either Azure A or Chloroacetate esterase technique. No statistical differences were found. The lack of increase in mast cell numbers was attributed to degranulation since numbers have been shown to be increased in perennial allergy when sections are examined ultrastructurally. PMID- 1919343 TI - Management of peritonsillar abscess. AB - A prospective, randomized clinical trial was conducted on 60 patients with confirmed peritonsillar abscess to: (1) compare the safety and efficacy of permucosal needle aspiration with that of incision and drainage; (2) assess whether admission to hospital and treatment with intravenous antibiotics is necessary; (3) culture the pus obtained, in order to decide on a rational antibiotic regime. Of the 60 patients, 30 were randomized to the needle aspiration group, and 30 to the incision and drainage group. The initial success rate was 87 per cent (26 of 30 patients) with needle aspiration, and 90 per cent (27 of 30 patients) with incision and drainage. Two patients required hospital admission, for rehydration and intravenous antibiotics. The commonest organisms cultured were streptococci (62 per cent); 97 per cent of all patients responded to penicillin. This study indicates that most patients with peritonsillar abscess may successfully and safely be treated by permucosal needle aspiration, and oral penicillin, on an out-patient basis. PMID- 1919344 TI - Retrograde intubation of the trachea. AB - Successful intubation can be accomplished in the majority of patients via direct laryngoscopy. However, situations frequently arise in which simple orotracheal intubation is contraindicated or impossible. In these situations retrograde tracheal intubation may be of particular use. This technique has been performed by novice physicians in cadavers, without difficulty or major complications. It has proved to be a quick, efficient and simple method to establish an endotracheal airway and should be a valuable adjunct for airway control. PMID- 1919345 TI - Tracheo-oesophageal puncture without tears: the forceps technique. AB - Certain problems have been encountered using a rigid endoscopic technique for tracheo-oesophageal puncture in voice restoration following laryngectomy. An alternative method is described using a modified curved abdominal forceps which allows quicker and more predictable access to the puncture site. PMID- 1919346 TI - Tracheo-oesophageal puncture: a review of problems and complications. AB - Tracheo-oesophageal puncture now has a well established role and in several units is now the principal means of speech rehabilitation following laryngectomy. Although not a difficult procedure, there are a number of problems and complications that may be encountered. With proper management these can usually be overcome and a useful voice achieved. This study looks at those problems in a series of 119 patients and discusses their management. PMID- 1919347 TI - Paediatric foreign bodies: the lessons of failure and near misses. AB - In this series of seven uncommon and complicated cases of foreign bodies in the aerodigestive tract of children, the difficulties in the management, and complications encountered are described. Various factors affecting the outcome of these cases have been highlighted. PMID- 1919348 TI - Stapedius tendon ossification: a rare cause of congenital conductive hearing loss. AB - Two cases are presented of bilateral conductive deafness in siblings. An initial presumptive diagnosis of otosclerosis was made in the first case, that of a nine year-old girl with a bilateral hearing loss of 45 dB. Exploratory tympanotomy revealed normal ossicles but the stapedius 'tendon' was found to be a solid bony bar fixing the stapes. Division of the 'tendon' resulted in normal ossicular mobility and return of hearing with closure of the air-bone gap. Identical ossification was found in her other ear, and some years later in both ears of one of her brothers. Similar surgery restored hearing successfully in each case. An acquired aetiology has been proposed in one of the three previously reported cases; this report, however, suggests the congenital nature of the anomaly. No previous cases have been described occurring in siblings. PMID- 1919349 TI - Bezold's abscess. AB - Since the introduction of antibiotics for the treatment of suppurative otitis media the incidence of complications from this disease has been greatly diminished. Acute mastoiditis, resulting in the deep neck abscess known as Bezold's abscess, has become very rare. A case of Bezold's abscess is presented with special reference to the clinical presentation and pathogenesis of this now uncommon condition. The variations in the routes of spread of the abscess in the fascial planes of the neck are described in detail. The difference between what is known today as a Bezold's abscess and the abscess that Bezold described in the early part of this century are presented. PMID- 1919350 TI - Latent mastoiditis: no room for complacency. AB - The administration of antibiotics in otitis media alters the natural course of the disease process. If the antibiotics used are inappropriate, or if dosage or duration of treatment is inadequate, an imminent intracranial complication may be masked. A case of latent mastoiditis presenting with Pott's puffy tumour is described. PMID- 1919351 TI - Bilateral acoustic schwannoma: post-operative hearing in the contralateral ear. AB - A patient with neurofibromatosis two (NF2) presented with bilateral acoustic neuroma. Pre-operative audiometry revealed a dead right ear and severe left-sided sensorineural hearing loss. Following surgical removal of the larger right acoustic neuroma we have documented a sensorineural improvement of 45 dB in the contralateral ear on pure tone audiometry, which as far as the authors are aware has not previously been described. PMID- 1919352 TI - Nasopharyngeal carcinoma with spinal secondaries. AB - Nasopharyngeal carcinoma has been reported to have a higher incidence of distant metastases as compared to other head and neck cancers. Distant metastases of nasopharyngeal carcinoma has been reported in the bones, lungs, liver, distant lymph nodes, brain and porta hepatis. This report presents a case of nasopharyngeal carcinoma with secondaries in the extradural space at the thoracic level of the spinal cord which hitherto has been an unreported site. PMID- 1919353 TI - A narcotic foreign body in the throat. AB - The impaction of a cannabis-filled condom in the upper oesophagus of a 28-year old prisoner is reported. The history was deceptive and smoking and drug abuse denied. The ENT surgeon being unaware of the identity of the drug faced tackling a possibly lethal foreign body, technically difficult to remove by the usual forceps method. (The Dormier basket is recommended for this task but we were unable to try it). Passage of the condom into the stomach occurred during attempted removal and its further progress was uneventful, indicating that gastroscopic removal of cannabis is unnecessary unless obstructive symptoms occur. PMID- 1919354 TI - Amelanotic melanoma metastatic to the epiglottis. AB - Metastasis of melanoma in the head and neck region is often reported but the report of amelanotic melanoma metastatic to the epiglottis is an extremely rare entity. This paper describes a patients previously treated for cutaneous amelanotic melanoma who developed metastatic tumour involving his epiglottis. This legion was successfully excised by a intra-oral approach combined with KTP/532 laser surgery. The paper also describes the diagnostic evaluation, management, operative technique and DNA analysis of this rare case. PMID- 1919355 TI - Acinic cell carcinoma of minor salivary gland origin. AB - The occurrence of acinic cell carcinoma in the minor salivary glands appears to be exceptional. A review of the English language literature revealed about 80 previously reported cases. In this paper, the clinical behaviour and pathological findings in three cases are reported. The tumours took their origin from the hard palate, soft palate and lower lip. The three cases presented with malignant clinical behaviour; all three recurred. In one case the local recurrence was multinodular with capsular infiltration. Two cases developed regional lymph node metastasis, and one metastasized to the lung and liver. In one the tumour infiltrated bony structures, and nerve in another. These cases tend to support the belief of some authors that acinic cell 'tumours' are clinically malignant and should be included in the carcinoma group. PMID- 1919356 TI - A rare presentation of tuberculosis of the cervical spine. AB - Tuberculosis may present in many different forms and is known to occur in the cervical spine and salivary glands. It may present as in this case, with the signs of spread before the initial infection becomes apparent. PMID- 1919357 TI - Acute bacterial thyroiditis presenting as otalgia. AB - A case of acute bacterial thyroiditis due to Haemophilus influenzae infection presenting as otalgia is reported. The features of this condition and the differential diagnosis from subacute (DeQuervains) thyroiditis are discussed. PMID- 1919358 TI - Parapharyngeal (retrostyloid)--third branchial cleft cyst. PMID- 1919359 TI - View from within: radiology in focus lateral pharyngeal diverticulum. AB - We report a case of a lateral pharyngeal diverticulum arising from the right vallecula. The aetiology and clinical features of these rare lesions are discussed. Diagnosis, which is difficult clinically, was made by barium swallow examination of the pharynx. The importance of contrast radiology in the investigation of pharyngeal symptoms is emphasized by this case. PMID- 1919360 TI - View from beneath: pathology in focus bilateral acinic cell tumours of the parotid gland. AB - A 55-year-old woman was operated because of bilateral parotid tumours which appeared with an interval of three years. Histopathologically, both of the tumours had characteristics typical of acinic cell tumour, so-called clear cell type. Both tumours were regarded to be multifocal. In the case of bilateral parotid tumours, acinic cell tumour should also be kept in mind and total parotidectomy is the treatment of choice. PMID- 1919361 TI - Intracellular survival of virulent Bordetella pertussis in human polymorphonuclear leukocytes. AB - Little is known regarding the interaction of Bordetella pertussis with polymorphonuclear leukocytes (PMNL) or the role PMNL play as an initial line of defense against B. pertussis infection. An in vitro system was developed to establish conditions for the study of phagocytosis and killing of virulent B. pertussis by human PMNL. Phagocytosis of B. pertussis strains BP504, BP165, and BP338 occurred by opsonization with anti-B. pertussis antibody, while autologous normal human sera did not induce significant phagocytosis. In PMNL bacterial killing assays virulent B. pertussis strains survived PMNL bactericidal activities while Escherichia coli controls were readily killed. Electron microscopy studies using acid phosphatase as a lysosomal marker strongly suggested that B. pertussis inhibits phagosome-lysosome fusion in PMNL. These results indicate that virulent B. pertussis strains are capable of surviving intracellularly within PMNL and that such survival may be due to inhibition of phagosome-lysosome fusion. PMID- 1919362 TI - Autonomous growth of human T-lymphotropic virus type I infected human lymphocytes treated with N-methyl-N'-nitro-N-nitrosoguanidine and ultraviolet rays. AB - Human T-cell cultures infected with human T-lymphotropic virus type I (HTLV-I) and interleukin-2 (IL-2)-dependent for their continuous growth were treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and then maintained in the medium containing phorbol 12-myristate 13-acetate (TPA). Cells achieved independence from IL-2 but became TPA-dependent for continuous growth. Multiple ultraviolet (UV) irradiations of TPA-dependent cells resulted in their autonomous growth. G band karyotype analysis revealed multiple chromosomal abnormalities that were seen in cells before and after MNNG treatment and UV irradiations, and those that were only seen in autonomously growing cells. Viral expression was found to be transiently enhanced in association with emergence of certain chromosomal changes. Exposure of HTLV-I infected cells to certain mutagens may promote the occurrence of the specific rearrangement of cellular genes responsible for regulation of cellular and viral replication and may lead these cells to neoplastic transformation. PMID- 1919363 TI - Purification and characterization of macromolecular phagocytosis activators released from platelets. AB - Substantial amounts of macromolecular activators of phagocytosis from platelets (MAPPs) were released in response to exposure of platelets to the specific agonists thrombin and collagen and to calcium ionophore A23187. Centrifugation of the platelets in culture medium also resulted in a release of MAPPs, but not when the platelets were frozen and thawed prior to centrifugation. In an experiment using outdated platelet concentrates, larger and smaller MAPPs (1-MAPP and s MAPP, respectively) were purified from the thrombin stimulated supernatant (PRPr plasma) by sequential steps of ammonium sulfate precipitation, delipidation with ethylacetate, ConA-Sepharose affinity chromatography, MONO Q anion exchange chromatography, and Superose 12 gel filtration. This procedure yielded 59,500 fold and 63,600-fold purified 1-MAPP (0.95 mg) and s-MAPP (0.41 mg), respectively, from 1,320 ml PRPr-plasma containing 84,500 mg protein. By gradient polyacrylamide gel electrophoresis the respective molecular weights (MW) of 1 MAPP and s-MAPP were 290-320 kd and 140-160 kd; isoelectric points were 5.6 and 4.6. Both MAPPs activated neutrophil phagocytosis of IgG-SRBC at concentrations in the range of 1 pM-100 nM. Indirect enzyme-linked immunosorbent assay (ELISA) and comparisons of the concentrations required for phagocytosis activation suggested that the MAPPs were not derived from fibronectin. PMID- 1919365 TI - Science in chiropractic clinical practice: identifying a need. AB - The chiropractic profession has resolved to establish chiropractic clinical care upon a scientifically acceptable foundation. In order for such an ambition to be realized, the cooperation and participation of field practitioners is required. A survey of chiropractors practicing in Australia demonstrated that respondents largely failed to appreciate the power of various research designs to provide clinical practice information. This paper suggests the chasm between professional resolve and clinical practice is not being adequately bridged at the level of field practitioners. PMID- 1919364 TI - Murine peritoneal macrophage gangliosides inhibit lymphocyte proliferation. AB - Gangliosides have been shown to act as immunoregulatory agents by altering proliferative responses of lymphocytes to both antigens and mitogens. Most early studies have utilized brain gangliosides and have required high concentrations. The role of endogenous gangliosides from macrophages has remained unexplored. In this study, thioglycolate-elicited murine peritoneal macrophage gangliosides were purified and added to cultures of murine lymphocytes. Nanogram amounts caused a profound inhibition of LPS-induced DNA synthesis of splenocytes and of purified B lymphocytes, without demonstrable cellular toxicity. No effect was seen using asialo-GM1. This effect was present across a wide range of lipopolysaccharide (LPS) doses. Nanogram amounts of macrophage gangliosides also inhibited concanavalin A (ConA)-mediated lymphocyte proliferation. Inhibition of LPS induced mitogenesis was present even if gangliosides were removed from the extracellular environment after 15-60 min of incubation prior to the addition of LPS. This inhibition was reversible with incubation of ganglioside pre-treated lymphocytes in medium containing serum. These inhibitory properties of macrophage gangliosides are distinct from those found in studies using brain gangliosides, and support a potential role for macrophage gangliosides as negative modulators of lymphocyte proliferation. PMID- 1919366 TI - Health Beliefs Model as a template for measurement of intern satisfaction in an ambulatory care clinical training program. AB - The Health Beliefs Model was originally developed in the 1950s to assess patient behavior toward preventative health strategies, and has evolved into a tool for measuring a variety of health related topics. Interns in an ambulatory care clinical training program were asked to complete a 62 item self-administered questionnaire based on concepts central to a modified Health Beliefs Model for assessment of their satisfaction with their internship program. A logistic regression was undertaken to identify relationships between interns' perceptions toward susceptibility and seriousness of illness, delivery of health care through outpatient clinics, supervisory professional personnel and their overall internship satisfaction rating. The data implies that the modified Health Beliefs Model is of value in predicting intern satisfaction. PMID- 1919367 TI - Morton's neuroma. AB - Morton's "neuroma" is a perineurofibrosis of an interdigital nerve. The authors describe various factors that may be responsible for the development of this lesion and relate this information to two case histories. In these cases, treatment with manipulation, various physical therapy modalities, and/or foot orthotics, resulted in the successful resolution of symptoms. PMID- 1919368 TI - Stop paradigm erosion. PMID- 1919369 TI - The physics of spinal manipulation. Part I. The myth of F = ma. PMID- 1919370 TI - Is there a chiropractic science? PMID- 1919371 TI - Interrater reliability of roentgenological evaluation of the lumbar spine in lateral bending. PMID- 1919372 TI - Health-care reform and chiropractic in the 1990s. AB - The organization and finance of health care in the United States are likely to change dramatically during the 1990s. During the first half of the decade, pro competition strategies, which characterized the 1980s, are likely to continue. However, by the end of the decade, the country will probably adopt some form of national health care. After briefly discussing both possibilities, this paper investigates their likely impact on the future practice of chiropractic in the United States, and concludes with some policy recommendations. PMID- 1919373 TI - The inter- and intraexaminer reliability of a paraspinal skin temperature differential instrument. AB - An experiment was undertaken to determine the intra- and interexaminer reliability of a paraspinal skin temperature differential instrument. Nineteen pain-free female chiropractic college students participated as subjects for the investigation. Three separate areas of the spine (C4-T2, T4-T8 and L2-L5) were examined for concordance between two examiners. Additionally, intraexaminer reliability was tested by having each examiner repeat the scanning procedure. Concordance for whether a temperature differential existed in a particular area was evaluated with the Kappa statistic. Kappas ranged from 0.034 to 0.6591 and were all statistically significant (p less than 0.05). This represented slight to moderate reliability in the area C4-T2 and substantial agreement in the region T4 T8. The lumbar region could not be evaluated with the Kappa statistic due to limited variation. Following agreement for a positive finding in a given area, the numerical ratings were evaluated for agreement with the intraclass correlation coefficient (ICC). The first observation between examiners indicated fair agreement (ICC = 0.2756, p = 0.0478). The second observation between examiners had substantial agreement (ICC = 0.6402, p = 0.042). Intraexaminer agreement was moderate for one examiner (ICC = 0.5078, p = 0.0016). The other examiner showed an excellent level of agreement (ICC = 0.8588, p less than 0.001) between observations. PMID- 1919374 TI - Anatomical leg length inequality, scoliosis and lordotic curve in unselected clinic patients. AB - Anatomic leg length inequality (LLI) and various mechanical measures of the lumbar spine, particularly scoliosis, lordosis and Ferguson's angle, were analyzed retrospectively from the X-rays of 106 consecutive patients in a private chiropractic practice. Results showed that 40% of the subjects had LLI greater than 6 mm while 70% had LLI greater than 3 mm. These data compared closely with studies done by other investigators, indicating that our routine diagnostic X-ray procedure is sufficient for accurately determining LLI. Our most noteworthy finding was that patients with LLI greater than 6 mm often (53% of the cases) had scoliosis and/or abnormal lordotic curves. Altered lordotic curves comprised both hypo- and hyperlordosis with about equal frequency. The correlation coefficients between the amount of LLI and any of the parameters taken singly, however, were not significant. The results of this study indicate that while there is no strong correlation between any one of the particular postural adaptations to anatomic leg length deficiency, nevertheless at least one abnormal spinal adaptation (scoliosis or hypo-hyperlordosis) occurs in over half of subjects who have LLI greater than 6 mm. PMID- 1919376 TI - Skeletal applications of videofluoroscopy. PMID- 1919375 TI - Resolution of spasmodic dysphonia (focal laryngeal dystonia) via chiropractic manipulative management. AB - This paper discusses the case of a 46-yr-old male suffering from spasmodic dysphonia, a chronic disorder involving hyperadduction of the vocal mechanism and resultant vocal arrest. Attention is paid to the neural innervation of the intrinsic laryngeal musculature and postulated mechanisms of irritation which may be amenable to chiropractic manipulative therapy. The type of spinal adjustment and treatment schedule are discussed. PMID- 1919377 TI - Chiropractic reconsidered: the sociology of chiropractic. PMID- 1919378 TI - Legitimacy at the expense of narrowing of scope of practice: chiropractic in Canada. PMID- 1919379 TI - Distribution of QRST deflection areas in relation to repolarization and arrhythmias. AB - QRST area maps were calculated from a computer model of propagated excitation with nonuniform cycle length-dependent recovery. Vulnerability was independently assessed as fibrillation threshold (FT). Separate effects of varied range and mean recovery durations on FT and QRST maps were determined. FT was inversely related to the range of recovery durations and that range was related to QRST area map features including magnitude, nonuniformity, and gradients. Mean recovery duration was directly related to FT but did not alter QRST maps unless changes of recovery duration were localized. Locally decreased mean duration resulted in decreased FT and increased magnitude and nonuniformity and gradients in QRST maps. Locally increased mean duration had similar effects on QRST maps, but FT was increased. Results support the validity of QRST map features as markers of vulnerability due to disparity of recovery duration or locally decreased mean recovery duration but not due to widespread changes of mean duration or locally increased duration. PMID- 1919380 TI - Signal-averaged body surface mapping for the assessment of low-amplitude potentials. Detailed maps during early ventricular activation in normal subjects. AB - Body surface isopotential maps around early ventricular activation were investigated in 30 normal subjects by the use of the authors' signal-averaged body surface mapping system. The number of beats averaged was 96-154 (mean, 127). Two distinct patterns were recognized in the appearance of a maximum at the onset of ventricular activation: the maximum in the first type (n = 16) was located on the right anterior chest; the maximum in the second type (n = 14) was on the central or left anterior chest. The site of the earliest ventricular activation was considered to be different in each of these types. During early ventricular activation, 25 subjects (83%) had two minima: one was on the left lateral chest and the other was on the left back. The two minima probably reflect two different receding activation fronts in the ventricles. The data in the present study are important to the understanding of the early ventricular activation process, as well as the diagnosis of heart diseases in which this process is disturbed. PMID- 1919381 TI - Effects of sudden changes in cycle length and pacing site on canine cardiac surface QRST isoarea maps. AB - The effects of changes in paced cycle length alone and changes in both paced cycle length and site of pacing on canine cardiac surface QRST isoarea maps were studied. The correlations between QRST isoarea maps acquired during right ventricular pacing at 900 ms and 700 ms averaged 0.97. The correlations between maps acquired during RV pacing at 900 ms and 500 ms averaged 0.94. The root mean square value of QRST areas progressively decreased as cycle length was decreased from 900 ms to 700 ms and then to 500 ms. This suggests that the pattern of distribution of repolarization properties remained the same and the magnitude of difference in repolarization properties decreased as cycle length was decreased. The correlation coefficients of QRST isoarea maps acquired during RV pacing at 900 ms and those acquired during left ventricular pacing at 700 ms and 500 ms averaged 0.74 +/- 0.01 and 0.68 +/- 0.03, respectively. These correlations were lower than those associated with a change in pacing cycle length alone. Root mean square differences in QRST areas recorded during changes in both pacing site and pacing cycle length were greater than the differences associated with change in cycle length alone. This suggests that changes in activation sequence altered repolarization properties more than they were altered by changes in cycle length alone. QRST isoarea maps have been proposed for assessing arrhythmia vulnerability. The results of this study provide a framework for interpreting QRST isoarea maps acquired during supraventricular tachycardias, premature ventricular complexes, and sustained ventricular tachycardias. PMID- 1919382 TI - Characterizing His-Purkinje system signals observed at the body surface. A model study. AB - A computer model of the His-Purkinje system (HPS), based on human geometry, has been developed and used in conjunction with an atrial model and an inhomogeneous torso model to calculate electrocardiograms (ECGs) and isofield potential and magnetic maps. The calculated electric potential maximum for penetrating His bundle (HB) activity is 0.6 microV, somewhat smaller than reported by others. A calculated ECG of combined atrial and HPS activity indicates that atrial repolarization contributes to the ramp pattern observed in the PR segment. Simulated isofield distributions indicate two features that should be present in serial-measured HPS maps: (1) maps preceding HB activity should be included to illustrate the nature of the onset of HB activity and (2) maps should show a change in the location and magnitude of the extrema commensurate with the change in direction and magnitude of the source current circumscribed by the anatomy of the HB and bundle branches. PMID- 1919383 TI - Evaluation of the electrocardiographic transitional zone by cardiac computed tomography. AB - The relationship between shift of the transitional zone on the standard 12-lead electrocardiogram (ECG) and anatomical rotation of the heart in one plane was studied by cardiac computed tomography (CT). Based on the position of the transitional zone, 102 subjects were divided into 3 groups: the normal transitional zone (NT) group (31 subjects), clockwise rotation (CWR) group (30 subjects), and counterclockwise rotation (CCWR) group (41 subjects). The left sided angle between the interventricular septum and horizontal axis of the body (the septal angle) was determined on the cardiac CT and compared among the three groups. The angle was 51.8 degrees +/- 6.8 degrees in the NT group, 38.2 degrees +/- 8.4 degrees in the CWR group, and 64.9 degrees +/- 10.4 degrees in the CCWR group. There were significant differences in the septal angle among the groups (p less than 0.05). The mechanism of CWR and CCWR could be attributed to the septal angle in about two-thirds of the cases (24/30 in CWR and 27/41 in CCWR). However, those not explained by the septal angle amounted to 6 (20%) of the CWR group and 14 (34%) of the CCWR group. Relatively higher positions of the precordial ECG leads, as observed in the vertical heart, appeared to be responsible for CWR in the 6 patients, and left septal fascicular block was suspected to be responsible for CCWR in the 14 patients. These data indicate that about two-thirds of CWR and CCWR can be explained by anatomical rotation of the heart in one plane around the long axis, but other factors appear to be responsible for such electrocardiographic findings in the remaining one-third of cases. PMID- 1919384 TI - Electrophysiological mechanisms of cocaine-induced cardiac arrest. A possible cause of sudden cardiac death. AB - The hypothesis that cocaine intoxication results in cardiac arrest by producing a block of the propagation of the action potential, without loss of pacemaker function, was tested in rat cardiac tissues. In spontaneously active sinoatrial preparations, cocaine exerted a dose-dependent negative chronotropic action, which was not modified by atropine or propranolol. Sinus node arrest was never observed. Instead, cocaine produced sinoatrial block. The mechanism of this block involved a fall in the resting potential and a decrease in the amplitude and Vmax of phase 0 of the action potential of atrial fibers. In sinoatrial preparations and papillary muscles driven at 5 Hz., cocaine depressed the resting potential, the total amplitude, the overshoot of the action potential, and the Vmax of phase 0. Cocaine had a biphasic effect on the atrial action potential duration. The initial shortening was muscarinic. The prolongation was alpha-adrenergic mediated and probably the result of the inhibition of the transient outward current Ito. In papillary muscles, only the prolongation of the action potential occurred. In conclusion, the electrophysiological actions of cocaine can explain cardiac sudden death. The fall in the resting potential associated with the decrease in the amplitude of the action potential of contractile fibers will result in a block of the propagation of the action potential. Quiescence of the contractile fibers will occur while the sinus node is still generating action potentials at a rate compatible with life. PMID- 1919386 TI - Pseudo preexcitation syndrome. AB - During the course of investigation for palpitations, a 62-year-old man underwent exercise testing using a MARQUETTE CASE 12 computerized exercise testing system. By stage III of the modified Bruce protocol, the computer-generated electrocardiogram appeared to show the development of exercise-induced preexcitation. Closer examination of the raw unfiltered data showed this to be a computer-generated artifact rather than true preexcitation. This artifact arose due to inherent limitations common to all computerized exercise testing systems and emphasizes the need to always review raw data, even when a seemingly clear cut abnormality is present on a computer-averaged electrocardiogram. PMID- 1919385 TI - Evidence that cocaine slows cardiac conduction by an action on both AV nodal and His-Purkinje tissue in the dog. AB - The effects of intravenous cocaine (2 mg/kg) were tested on several indices of cardiac electrical activity in sedated dogs. These included sinus rate, PR, AH, and HV intervals; AV nodal effective refractory period (AVNERP); ventricular effective refractory period; QRS duration; and the QT interval. Cocaine induced significant changes in six control animals with an intact-functioning autonomic nervous systems. After pharmacologic autonomic blockade with propranolol plus propantheline, cocaine increased the PR interval (+ 11 +/- 4.0 ms, p less than 0.05), primarily by slowing conduction at the AV nodal level. However, with constant atrial pacing at a rate above the sinus cycle length, prolongation of both the AH and the HV intervals (+ 15 +/- 2.5 and 6.7 +/- 1.7 ms, respectively) occurred. There was also a significant increase in the AVNERP (+ 29 +/- 5.9 ms, p less than 0.05). Consistent with the observed rate-dependent HV prolongation, cocaine decreased the rate of rise of phase 0 of the transmembrane action potential of Purkinje fibers. These data indicate that cocaine impairs cardiac conduction by direct actions on AV nodal and His-Purkinje cells. PMID- 1919387 TI - Giant T waves simulating apical hypertrophic myocardiopathy that disappear with sodium nitroprusside administration. Case report of pheochromocytoma. AB - Giant inverted T waves (amplitude greater than 1 mV) in precordial leads have been described in various disease processes. However, the pathophysiology of these anomalies has not been studied in depth. This paper analyzes repolarization abnormalities occurring in a case of pheochromocytoma in which giant T waves were unaffected by alpha-adrenergic blockade but were affected by administration of sodium nitroprusside. It is postulated that the probable cause of this aberration is myocardial ischemia of noncoronary origin resulting from an imbalance of supply and demand of oxygen that is relieved by the hemodynamic action of nitroprusside when left ventricular wall stress is reduced. PMID- 1919388 TI - A low molecular weight endometrial secretory protein which is increased by ovine trophoblast protein-1 is a beta 2-microglobulin-like protein. AB - Ovine trophoblast protein-1 (oTP-1), stimulates the secretion of several proteins in explant culture of day-12 cyclic ovine endometrium. We partially purified and identified one of these proteins, an 11,000 Mr, pI approx. 6 protein by N terminal amino acid sequencing and immunoprecipitation using antibody to human beta 2-microglobulin. The protein was purified from cultures of endometrium collected from day-16 pregnant ewes. The N-terminal amino acid sequence was 40 55% homologous to beta 2-microglobulin from a variety of species. Antibody to human beta 2-microglobulin immunoprecipitated the protein and another protein of similar molecular weight but more acidic pI. Using immunoprecipitation of radiolabelled proteins from culture, we demonstrated that oTP-1 increased production of this protein by 40% (P less than 0.05). We conclude that oTP-1 increases the secretion of a beta 2-microglobulin-like protein from day-12 non pregnant endometrium in culture. PMID- 1919389 TI - Is cancer in women preventable by hormone manipulation? PMID- 1919390 TI - Binding sites for LH in Candida albicans: comparison with the mammalian corpus luteum LH receptor. AB - We have described recently the presence of binding sites for human LH (hLH) and human chorionic gonadotrophin (hCG) in microsomal and cytosol fractions prepared from the dimorphic, pathogenic fungus, Candida albicans. We have now compared the properties of Candida LH/hCG-binding sites with those of the ovine luteal LH receptor. Sheep luteal LH-binding sites were associated with luteal membranes, and little or no binding activity was present in cytosol fractions. In contrast, significant LH/hCG-binding activity was present in Candida cytosol. Moreover, there were marked differences in sensitivity to inhibition by metal ions, association and dissociation rates, and affinity constants between sheep and Candida LH-binding sites. Scatchard plots of 125I-labelled hLH binding to sheep luteal receptors demonstrated a single high-affinity component (association constant (Ka) 0.3 litres/pmol) which was displaceable by hCG. In contrast, Scatchard plots of binding to Candida microsomes and cytosol fractions demonstrated two components, one with high affinity (Ka 0.18 litres/pmol) and low capacity and a second site with lower affinity (Ka 4 litres/nmol) and high capacity, both of which were displaceable by unlabelled hCG. Gel permeation chromatography of cytosol demonstrated two distinct peaks of LH-binding activity with approximate molecular weights of greater than 1,000,000 and 30,000-50,000. Scatchard plots of 125I-labelled hLH binding to the higher molecular weight peak demonstrated a single, high-affinity LH-binding site (Ka 0.18 litres/pmol), whereas the lower molecular weight fraction contained both high- (Ka 0.17 litres/pmol) and low-affinity (Ka 4 litres/nmol) LH-binding sites. Both partially purified and highly purified hCG and hLH preparations displaced binding of 125I labelled hLH and hCG to sheep luteal LH receptors at similar concentrations. 125I labelled hLH/hCG binding to Candida membranes was also displaceable by low levels (ng) of partially purified hCG preparations, but much higher levels (micrograms) of highly purified hLH and hCG were required. This paradoxical observation suggested the presence of radiolabelled contaminants, or damaged forms induced during radioiodination of hormone tracers, which can bind more strongly to Candida membranes than unlabelled hCG and hLH but which do not bind to sheep LH receptors. However, no evidence for hLH tracer contaminants with differential binding to Candida and sheep luteal receptors was obtained following gel exclusion chromatography or fractionation on Concanavalin A-Sepharose. (Although three distinct 125I-labelled hLH fractions were resolved on Concanavalin A Sepharose, presumably reflecting differences in their carbohydrate compositions, all three tracer peaks bound equivalently to both Candida membranes and ovine luteal LH receptors).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919392 TI - Effects of follicular fluid administration on serum bioactive and immunoactive FSH concentrations and compensatory testicular hypertrophy in hemicastrated prepubertal rats. AB - In prepubertal rats, removal of one testis (hemicastration) results in increased FSH secretion and a compensatory hypertrophy of the remaining testis. To determine whether these two events are related, testis weight was measured after inhibin-rich porcine follicular fluid (FF) was administered to hemicastrated rats twice daily for 14 days to block the compensatory rise in FSH. After hemicastration, serum immunoreactive FSH concentration approximately doubled and testis weight was increased by approximately 60%. A slight but non-significant increase in serum bioactive FSH was also observed. Treatment of hemicastrated rats with FF completely prevented the increase in serum FSH and compensatory growth of the remaining testis, whereas concomitant treatment of these animals with ovine FSH reversed the inhibitory effects of FF. Serum inhibin concentrations were determined using two radioimmunoassay (RIA) systems; one assay utilized an antiserum generated against intact bovine inhibin and the other was directed against an alpha-inhibin fragment. Both assays showed a decline in inhibin levels following hemicastration. In addition, increases in serum inhibin concentrations were observed following FF administration in both RIAs; however, the relative increase in inhibin over levels in hemicastrated rats was greater using the intact inhibin assay. In summary, these data suggest that the increase in FSH concentrations after hemicastration is related to a reduction in inhibin levels, and that this FSH rise is a primary signal for initiating compensatory testicular hypertrophy in prepubertal rats. Furthermore, exogenous FSH administration overcame the inhibitory effects of FF on the testes, suggesting that inhibin may not act directly at the gonadal level. PMID- 1919391 TI - Avidin and ovalbumin induction by progesterone in chicken oviduct detected by sensitive immunoenzymometric assays. AB - This study describes sensitive immunoenzymometric assays (IEMAs) for chicken avidin and ovalbumin, markers of cytodifferentiation and action of progesterone and oestrogen in the oviduct magnum mucosa. The determination range was 0.5-100 ng/ml and the detection limit 0.1 ng/ml in both IEMAs. The intra- and interassay coefficients of variation, measured from chicken tissue supernatants, averaged below 6 and 10% respectively. IEMAs correlated well with the radioimmunoassays for avidin and ovalbumin previously developed in our laboratory, and with the widely used [14C]biotin-binding method for avidin. Using an IEMA, we found avidin induction with low concentrations of progesterone in the differentiated oviduct of oestrogen-pretreated chicks. The induction has not been detected previously by less sensitive methods. Avidin was induced by all given doses of progesterone (0.2-200 mg/kg in vivo for 24 h after a short oestrogen treatment), the response being dose-dependent at doses of 0.2-20 mg progesterone/kg body weight, the maximum avidin production being about 70 micrograms/g tissue. Ovalbumin was induced at doses of 2-200 mg progesterone/kg body weight without variations in the responses, being about 35 mg/g. The mean content of avidin in the oviduct of laying hens was 58.1 micrograms/g, and of ovalbumin 74.9 mg/g. Minimal traces of avidin and ovalbumin were found in the oviduct after hatching (0.3 and 5 micrograms/g respectively); however, progesterone did not have an effect on this expression. Sensitivity, rapidity and practicability, together with non radioactivity, are the main advantages of the present IEMAs for chicken avidin and ovalbumin. PMID- 1919393 TI - The effect of uninephrectomy on osteocalcin metabolism in sheep: a direct evaluation of renal osteocalcin clearance. AB - Indirect evidence has suggested that the kidney is a major organ of clearance for osteocalcin, a circulating marker of osteoblast function. The objectives of the present study were (1) to confirm the role of the kidney in osteocalcin clearance (2) to quantify the contribution of extrarenal sites and (3) to investigate the renal mechanism(s) of osteocalcin clearance. Plasma osteocalcin levels, osteocalcin plasma clearance rate (PCR) and plasma production rate (PPR) were determined in oophorectomized (OX) and uninephrectomized oophorectomized (UOX) sheep. The osteocalcin renal extraction efficiency (REE) and the effective renal plasma flow (ERPF) were measured, and the osteocalcin renal clearance rate (RCR) was calculated. The osteocalcin PCR was reduced significantly in UOX compared with OX sheep (2.0 +/- 0.1 (n = 9) vs 2.5 +/- 0.1 litres/h (n = 44); P less than 0.0005). In UOX sheep with plasma creatinine levels less than or equal to 130 mumol/l, the osteocalcin REE was 9 +/- 1.3% and the osteocalcin RCR was 50-91% of osteocalcin PCR (n = 4). In UOX sheep with plasma creatinine levels in the range 100-440 mumol/l, there was a linear relationship between osteocalcin PCR and ERPF; the osteocalcin RCR was related to the osteocalcin PCR (RCR = 0.9 x PCR - 0.50). Intravenous infusion of the synthetic glucocorticoid triamcinolone acetonide (TA) in UOX sheep led to marked decrements in plasma osteocalcin levels and the osteocalcin PPR, and a significant increase in the osteocalcin PCR. These changes were accompanied by a 44% increase in ERPF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919394 TI - Testicular oxytocin: effects of intratesticular oxytocin in the rat. AB - The long-term effects of oxytocin administration on the testis were studied using intratesticular implants. Adult male rats had an Accurel device containing 20 micrograms oxytocin (releasing approximately 200 ng/day) implanted into the parenchyma of each testis; control animals received empty devices. The animals were killed at weekly intervals for 4 weeks. Some animals were perfused and the testes processed for light and electron microscopy. Blood was collected from the remaining animals for the measurement of testosterone, dihydrotestosterone, LH, FSH and oxytocin; epididymal sperm counts were measured and the testes were extracted and radioimmunoassayed for testosterone, dihydrotestosterone and oxytocin. Long-term administration of oxytocin resulted in a significant reduction in testicular and plasma testosterone levels throughout the 4-week period examined and, after 14 days of treatment, lipid droplets were seen in the Leydig cells of treated but not control animals. Concentrations of dihydrotestosterone in the plasma and testes of the oxytocin-treated animals, however, were significantly elevated after 7 and 14 days and at no time fell below control values. Plasma FSH levels were also lower in the oxytocin-treated animals. Intratesticular oxytocin treatment did not affect LH or oxytocin concentrations in the plasma, epididymal sperm counts or the number of Leydig cells in the testis. Empty Accurel devices had no effect on testicular morphology. This study provides the first evidence that oxytocin in vivo can modify steroidogenesis in the testis. PMID- 1919395 TI - Regulation by thyroid status of c-myc, c-fos and H-ras mRNAs in the rat myocardium. AB - Effects of thyroid status on expression of a variety of myocardial genes, such as those encoding contractile proteins, have been reported, as well as interactions between thyroid hormones and developmental and haemodynamic regulation of contractile protein synthesis. In addition, it is clear that developmental and haemodynamic factors regulate expression of specific proto-oncogenes, including c myc, c-fos and H-ras, in the myocardium but the effect of thyroid status on such proto-oncogene products, which are proposed to play a critical signal-transducing role in the heart, has been previously unexplored. In order to determine whether changes in thyroid status are associated with changes in expression of these putative intracellular signals, we examined the effect of hypothyroidism and tri iodothyronine (T3) treatment on myocardial levels of c-myc, c-fos and H-ras mRNAs in the rat. The induction of hypothyroidism was associated with a marked increase in myocardial c-myc, c-fos and H-ras mRNAs, changes reversed by 72 h of T3 replacement. Administration of T3 to euthyroid rats had no significant effect on myocardial c-myc or c-fos mRNAs, but inhibition of H-ras mRNA by T3 was evident. These observations demonstrating influences of thyroid status on expression of specific proto-oncogenes suggest that thyroid hormones, as well as exerting direct effects on expression of functionally important myocardial genes, also interact with the cellular transduction pathways mediated by the products of the c-myc, c-fos and H-ras genes. PMID- 1919396 TI - Progesterone receptor in the mammary tissue of pregnant and lactating gilts and the effect of tamoxifen treatment during late gestation. AB - An isotope exchange assay using [3H]progesterone was used to examine progesterone receptor moieties in cytosolic extracts obtained from mammary tissue of gilts over the course of pregnancy and lactation, and during treatment of pregnant gilts with tamoxifen. Scatchard analysis was used to determine the concentrations and dissociation constants of progesterone receptors. The concentration of progesterone receptor was high at the onset of pregnancy (1394 fmol/mg DNA), fell to a nadir at 45 days (36 fmol/mg DNA), increased to a second maximum at 75 days (1232 fmol/mg DNA) and declined thereafter till parturition: the dissociation constant (Kd) of progesterone for its receptor remained stable during pregnancy with a mean Kd of 0.78 nmol/l. Progesterone receptors were not identifiable at day 21 of lactation. Treatment of pregnant gilts with tamoxifen (100 mg or 1.0 g/gilt per day orally identical to 0.70 or 7.0 mg/kg per day) did not affect the development of mammary structures or the ability to lactate at parturition; however, mammary progesterone receptor content in tamoxifen-treated animals tended to be lower than the controls at day 90 of pregnancy (15.7 +/- 1.56 vs 27.0 +/- 3.75 fmol/mg protein respectively). The results show that a temporal relationship exists between oestrogen concentrations in the circulation of pregnant gilts with progesterone receptor content in mammary tissue. PMID- 1919398 TI - Initial ovulation rate and follicle population after injection of inhibin neutralizing antiserum in the late-prepubertal rat. AB - In late-prepubertal female rats passive immunoneutralization of endogenous inhibin was achieved by injection of inhibin antiserum. Effects on follicle population, timing of sexual maturation, ovulation rate at first and second oestrus and serum FSH levels were studied. Rats were injected with antiserum, (non-immune) control serum from castrated sheep (castrated serum) or their IgG fractions, or with saline on day 33 or 3 or 2 days (days -3/-2) before the expected day of first ovulation, day 38.5 +/- 0.2 (n = 70). Blood was collected from different subgroups at 8, 24 and 48 h, and at first and second oestrus after injection. At necropsy, ovaries were histologically prepared for differential counting of follicles (48 h and first oestrus) and counting of corpora lutea (CL; first and second oestrus) as an index of ovulation rate. Results from rats injected with either serum or its IgG fraction were not different, as was the case when rats were injected with either castrated serum or saline. Thus, results from groups treated with antiserum and antiserum IgG were combined and labelled 'antiserum', and the castrated serum, castrated serum IgG and saline-treated groups were combined and labelled 'control'. The activity of inhibin-neutralizing antibodies in the circulation of antiserum-treated rats was reduced by 43% between 8 h and second oestrus after injection, as determined by the binding of purified bioactive radioiodinated 31 kDa bovine inhibin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919397 TI - Effect of the entero-pancreatic hormones, gastric inhibitory polypeptide and glucagon-like polypeptide-1(7-36) amide, on fatty acid synthesis in explants of rat adipose tissue. AB - The effect of gastric inhibitory polypeptide (GIP), glucagon-like peptide-1(7-36) amide, (GLP-1(7-36) amide), glucagon-like peptide-2 (GLP-2), glucagon and insulin on fatty acid synthesis in explants of rat adipose tissue from various sites was investigated. GIP, GLP-1(7-36) amide and insulin stimulated fatty acid synthesis, as determined by measuring the incorporation of [14C]acetate into saponifiable fat, in a dose-dependent manner, over the concentration range 5-15 ng/ml (0.87 2.61 nmol/l) for insulin and 0.5-7.5 ng/ml for GIP (0.10-1.50 nmol/l) and GLP-1(7 36) amide (0.15-2.27 nmol/l). Insulin and GIP caused a significantly greater stimulation of [14C]acetate incorporation into fatty acids in omental adipose tissue than in either epididymal or subcutaneous adipose tissue. Both GIP and GLP 1(7-36) amide had the ability to stimulate fatty acid synthesis within the physiological range of the circulating hormones. At lower concentrations of the hormones, GLP-1(7-36) amide was a more potent stimulator of fatty acid synthesis than GIP in omental adipose tissue culture; the basal rate of fatty acid synthesis was 0.41 +/- 0.03 pmol acetate incorporated/mg wet weight tissue per 2 h; at 0.10 nmol hormone/1 1.15 +/- 0.10 and 3.40 +/- 0.12 pmol acetate incorporated/mg wet weight tissue per 2 h for GIP and GLP-1(7-36) amide respectively (P less than 0.01). GLP-2 and glucagon were without effect on fatty acid synthesis in omental adipose tissue. The study indicates that GIP and GLP 1(7-36)amide, in addition to stimulating insulin secretion, may play a direct physiological role in vivo, in common with insulin, in promoting fatty acid synthesis in adipose tissue. PMID- 1919399 TI - Ovulation rate, follicle population and FSH levels in cyclic rats after administration of an inhibin-neutralizing antiserum. AB - Ovulation rate, follicle growth, serum FSH and oestradiol concentrations were studied after a single intraperitoneal injection of inhibin antiserum in 5-day cyclic rats. Control rats received (non-immune) serum from castrated sheep or saline. Rats were injected at 10.00 h on dioestrus-1 (D1), i.e. the day following the day of oestrus, or at 17.00 h on dioestrus-2 (D2). The ovaries were excised at necropsy 48 h after injection, or at first or second oestrus after injection. After routine histology fresh corpora lutea were counted and/or differential follicle counts were made. Results from rats injected with either (non-immune) serum from castrated sheep or with saline were not different and were therefore combined to form the control group. The activity of inhibin-neutralizing antibodies in the circulation of antiserum-treated rats was reduced by approximately 39% between 8 h and second oestrus after injection, as determined by the binding of purified bioactive radioiodinated 31 kDa bovine inhibin. Rats were injected on D1 and killed at first oestrus. The number of fresh corpora lutea was significantly higher in antiserum-treated rats than in controls (13.9 +/- 0.4 vs 11.8 +/- 0.4; P less than 0.05). Other rats injected on D1 were killed either 48 h or at the second oestrus after injection. Blood was collected 8, 16, 24 and 48 h and at first and second oestrus after injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919400 TI - Reduced serum concentrations of insulin-like growth factor-I (IGF-I) in protein restricted growing rats are accompanied by reduced IGF-I mRNA levels in liver and skeletal muscle. AB - The serum concentration of insulin-like growth factor-I (IGF-I) is reduced in growing rats fed a low-protein diet, and this decrease is age-dependent, being more pronounced in younger animals. To determine whether this decrease in serum IGF-I is related to a decrease in IGF-I mRNA, growing female rats were given free access to either a 15% protein-sufficient or a 5% protein-deficient diet for 1 week. Protein restriction in 4-week-old rats decreased body weight gain by 44% (P less than 0.001 compared with 4-week controls), serum IGF-I concentration by 67% (P less than 0.001) and liver IGF-I mRNA abundance by 51% (P less than 0.001). During week 6, protein restriction for 1 week resulted in a 20% increase in food intake with no change in weight gain, a 38% reduction in serum IGF-I (P less than 0.001 compared with 6-week controls) and a 39% decrease in liver IGF-I mRNA (P less than 0.001). The serum IGF-I concentration was highly correlated (r = 0.80; P less than 0.001) with the hepatic IGF-I mRNA concentration. Skeletal muscle IGF I mRNA abundance was also decreased significantly by protein restriction (37% at week 4, P less than 0.001, and 24% at week 6, P less than 0.01) and was closely correlated (r = 0.71; P less than 0.001) with body weight gain. Liver GH-binding protein and GH receptor mRNA abundance were reduced by 1 week of protein deprivation at week 6 but not at week 4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919401 TI - Influence of nutritional status on growth hormone-dependent circulating somatomedin-C activity in mature sheep. AB - The effect of daily administration of ovine GH for a period of 4 weeks on somatomedin-C biological activity in plasma was investigated in mature Merino sheep fed a maintenance energy intake (low plane; LP) or 1.6 times this amount (high plane; HP). The GH treatment resulted in a significant (P less than 0.05) increase in plasma GH levels in blood samples collected 23.5 h after each daily injection in both LP and HP groups. Plasma concentrations of somatomedin-C activity and insulin were significantly stimulated to a maximum level by the third GH injection and remained at this level for 7 days. Subsequently, circulating levels of both hormones fell to 40-50% of the peak response to GH and returned to basal levels within 48 h of the cessation of GH injections. In the HP group the response of plasma insulin and somatomedin-C activity to GH injection was greater than in the LP group. PMID- 1919402 TI - An evaluation of four methods of root canal preparation using 14C urea. AB - One-hundred twenty single-rooted teeth were used in vitro in order to compare the four following methods of endodontic preparation: manual, Giromatic, MM 3000 Sonic Air with, and sonic air without the contact shaping technique. Each endodontic preparation was filled according to the McSpadden technique. Teeth were immersed in 14C urea. Radioactivity was evaluated qualitatively by autoradiography and quantitatively by scintigraphy. Data were statistically analyzed with a nonparametric test. The results show that the highest degree of leakage occurs with the manual method and that for the three other methods, maximum leakage takes place near the apices. PMID- 1919403 TI - The effects of Canal Master, Flex-R, and K-Flex instrumentation on root canal configuration. AB - The purpose of this study was to compare the Canal Master instrument and instrumentation technique (CM/CMI) to Flex-R files used with a "balanced force" technique (FR/BF) and K-Flex files used with a step-back filing technique (KF/SB). Thirty-six root canals in extracted human mandibular molars were equally divided into three groups. The roots were sectioned, then photographed and evaluated before and after instrumentation. Evaluation included canal shape, direction and extent of transportation, amount of dentin removed, and centering ability. Canal Master instrumentation and Flex-R/balanced force techniques both produced more round preparations than the K-Flex/step-back. All three techniques resulted in canal transportation, although to varying degrees. Flex-R/balanced forces and Canal Master instrumentation transported very little up to a #30, and Canal Master instrumentation transported significantly less after the #45 instrument at mid-root. K-Flex/step-back removed the most dentin while Flex R/balanced force removed the least in the apical sections and Canal Master instrumentation removed the least at mid-root. The ability of Canal Master instrumentation to keep instruments centered in the canals was significantly better than for K-Flex/step-back. PMID- 1919404 TI - Histological evaluation of ultrasonic debridement comparing sodium hypochlorite and water. AB - Twenty extracted human mandibular first and second molars with mesial canal curvatures of 18 to 35 degrees were randomly divided into two groups. Following routine endodontic access and canal length determination one of the mesial root canals was ultrasonically instrumented, using tap water in the first group or 2.6% sodium hypochlorite irrigation in the other. In both groups the other mesial canal was used as a control. The mesial roots were decalcified, serially sectioned, and stained with hematoxylin and eosin. Wall planing and soft tissue debridement were blindly evaluated using the light microscope. Mean canal wall planing and soft tissue debridement scores were compared by multiple t tests. Sodium hypochlorite, in conjunction with ultrasonic instrumentation, was more effective than tap water in wall planing when the entire root length was considered. Sodium hypochlorite, in conjunction with ultrasonic instrumentation, was more effective than tap water in soft tissue debridement in the middle third of the canal. Both irrigants were ineffective in conjunction with ultrasonic instrumentation in removing soft tissue from the main canal, the isthmus between canals, the canal fins, and the multiple branches or deltas often encountered in the apical one-third of the canal. PMID- 1919405 TI - Scanning electron microscopy observations on the penetration and structure of resin tags in bleached and unbleached bovine enamel. AB - The purpose of this study was to determine the effect of hydrogen peroxide on the ability of composite resin to penetrate bovine enamel etched with phosphoric acid. In a previous investigation, the flattened enamel surfaces of extracted bovine incisors were immersed in either saline (control) or 35% hydrogen peroxide (experimental) for 5 or 30 min before or after acid etching with 37% phosphoric acid gel for 60 s. A standard-sized light-cured resin cylinder was then bonded to the enamel surface. The specimens were stored in a water bath at 37 degrees C for 1 day or 7 days, after which the enamel-resin bond was tensile tested to failure. Sixteen of the failed specimens (eight control and eight experimental) were randomly selected for the present scanning electron microscopic study to evaluate the appearance of the resin tags at the resin-enamel interface. In the control specimens, the tags were well defined and contiguous with resin which was uniformly adherent to the enamel surface. In the experimental specimens, large areas of the enamel surface were free of resin. When tags were present, they were fragmented, poorly defined, and penetrated to a lesser depth than in the saline controls. The changes observed suggest that there may be interaction between resin and residual peroxide at or near the enamel surface. PMID- 1919406 TI - Lack of correlation between the amount of eugenol released from zinc oxide eugenol sealer and cytotoxicity of the sealer. AB - The purpose of this study was to examine a possible correlation between the eugenol released from a zinc oxide-eugenol sealer (Canals) and the degree of cytotoxicity. The cytotoxicity and eugenol release from root canal filling material containing eugenol was examined for test solutions at several experimental periods. No positive correlation was found between eugenol release and cytotoxicity of the root canal filling material. PMID- 1919407 TI - Maxillary molars with two palatal roots: a retrospective clinical study. AB - Clinical records and radiographs were reviewed for 15 patients who had endodontic treatment performed on 16 maxillary molars with two palatal roots. These cases, plus six extracted teeth or slides, were evaluated. From the morphology of these roots, a classification of three types is proposed. PMID- 1919408 TI - A 2-day decompression: a case report of a maxillary first molar. AB - A case report of a maxillary first molar is presented in which a drainage tube from a decompression procedure was removed 2 days following placement. The oral surgeon who removed the tube scheduled the patient for surgical enucleation of the large periapical lesion. The surgical appointment was subsequently cancelled and routine endodontic follow-up showed continued osseous repair at 3, 6, and 12 months. The decompression of a large periapical lesion is a conservative alternative to surgical enucleation. PMID- 1919409 TI - Remedy for dental dam leakage problems. AB - Denture adhesive paste is a very sticky adherent substance. When combined with zinc oxide powder, a creamy mixture results. This provides an ideal caulking substance to use as a sealing material during endodontic procedures where leakage of oral fluids is anticipated or has occurred after dental dam placement. Requirements for an ideal leakage preventative are listed. PMID- 1919410 TI - Energetics and power output of isolated fish fast muscle fibres performing oscillatory work. AB - Fast myotomal muscle fibres were isolated from the cod (Gadus morhua L.) and the energy cost of contraction was measured under conditions simulating swimming. Fibre bundles were subjected to sinusoidal cycles of shortening and lengthening about their in situ fibre length, and stimulated at selected phases in each cycle. The preparations were poisoned with iodoacetic acid and bubbled with nitrogen to block the synthesis of ATP. After an initial rapid decline over the first 10 cycles, force and net work remained steady in some cases for up to 64 oscillatory length cycles, but more commonly declined slowly after about 30 cycles. The total mechanical work performed increased largely in proportion to the number of work cycles. At the end of each experiment fibres were frozen in isopentane cooled in liquid nitrogen and metabolite concentrations determined by high performance liquid chromatography (HPLC) and enzymatic analysis. Concentrations of adenylates did not differ significantly from control values, although a significant increase in IMP concentrations at 64 cycles accounted for the maintenance of relatively high energy charge values. Creatine (C) concentrations increased and creatine phosphate (CP) concentrations decreased, implying a tight coupling of the ATP/ADP reaction to the CP/C reaction. Muscle economy was calculated as the positive work performed during a work cycle divided by the total chemical energy expended. These values (approx. 7 mJ mumol-1) were found to be independent of the number of work cycles performed, although a trend to increase was observed. Muscle efficiency values, calculated assuming a Gibb's force free energy change for CP splitting in vivo of 55 kJ mol-1, were in the range 12-23%. PMID- 1919411 TI - Efficiency of energy conversion during shortening of muscle fibres from the dogfish Scyliorhinus canicula. AB - Force and heat production were measured during isovelocity shortening of tetanized white myotomal muscle fibres from the dogfish at 12 degrees C. For each fibre preparation a range of velocities was used. Mechanical power was calculated from force X velocity of shortening. The rate of total energy output during shortening was evaluated as the sum of mechanical power and the rate of heat production. The ratio of mechanical power to total energy rate was taken as a measure of efficiency of energy conversion to mechanical power during shortening. Efficiency was maximal and varied little in the range of shortening velocities 0.42-0.89 fibres lengths s-1 (0.11-0.23 Vmax); maximal efficiency was 0.33 +/- 0.01 (+/- S.E.M., N = 23 measurements on seven fibre bundles). The efficiency of the white fibres from dogfish was less than that measured in the same way in earlier experiments on frog muscle and tortoise muscle. PMID- 1919412 TI - Leg design in hexapedal runners. AB - Many-legged animals, such as crabs and cockroaches, utilize whole-body mechanics similar to that observed for running bipeds and trotting quadrupedal mammals. Despite the diversity in morphology, two legs in a quadrupedal mammal, three legs in an insect and four legs in a crab can function in the same way as one leg of a biped during ground contact. To explain how diverse leg designs can result in common whole-body dynamics, we used a miniature force platform to measure the ground reaction forces produced by individual legs of the cockroach Blaberus discoidalis. Hexapedal runners were not like quadrupeds with an additional set of legs. In trotting quadrupedal mammals each leg develops a similar ground reaction force pattern that sums to produce the whole-body pattern. At a constant average velocity, each leg pair of the cockroach was characterized by a unique ground reaction force pattern. The first leg decelerated the center of mass in the horizontal direction, whereas the third leg was used to accelerate the body. The second leg did both, much like legs in bipedal runners and quadrupedal trotters. Vertical force peaks for each leg were equal in magnitude. In general, peak ground reaction force vectors minimized joint moments and muscle forces by being oriented towards the coxal joints, which articulate with the body. Locomotion with a sprawled posture does not necessarily result in large moments around joints. Calculations on B. discoidalis showed that deviations from the minimum moments may be explained by considering the minimization of the summed muscle forces in more than one leg. Production of horizontal forces that account for most of the mechanical energy generated during locomotion can actually reduce total muscle force by directing the ground reaction forces through the leg joints. Whole-body dynamics common to two-, four-, six- and eight-legged runners is produced in six-legged runners by three pairs of legs that differ in orientation with respect to the body, generate unique ground reaction force patterns, but combine to function in the same way as one leg of a biped. PMID- 1919413 TI - Coordination of locomotor and cardiorespiratory networks of Lymnaea stagnalis by a pair of identified interneurones. AB - 1. The morphology and electrophysiology of a newly identified bilateral pair of interneurones in the central nervous system of the pulmonate pond snail Lymnaea stagnalis is described. 2. These interneurones, identified as left and right pedal dorsal 11 (L/RPeD11), are electrically coupled to each other as well as to a large number of foot and body wall motoneurones, forming a fast-acting neural network which coordinates the activities of foot and body wall muscles. 3. The left and right sides of the body wall of Lymnaea are innervated by left and right cerebral A cluster neurones. Although these motoneurones have only ipsilateral projections, they are indirectly electrically coupled to their contralateral homologues via their connections with L/RPeD11. Similarly, the activities of left and right pedal G cluster neurones, which are known to be involved in locomotion, are also coordinated by L/RPeD11. 4. Selective ablation of both neurones PeD11 results in the loss of coordination between the bilateral cerebral A clusters. 5. Interneurones L/RPeD11 are multifunctional. In addition to coordinating motoneuronal activity, they make chemical excitatory connections with heart motoneurones. They also synapse upon respiratory motoneurones, hyperpolarizing those involved in pneumostome opening (expiration) and depolarizing those involved in pneumostome closure (inspiration). 6. An identified respiratory interneurone involved in pneumostome closure (visceral dorsal 4) inhibits L/RPeD11 together with all their electrically coupled follower cells. 7. Both L/RPeD11 have strong excitatory effects on another pair of electrically coupled neurones, visceral dorsal 1 and right parietal dorsal 2, which have previously been shown to be sensitive to changes in the partial pressure of environmental oxygen (PO2). 8. Although L/RPeD11 participate in whole-body withdrawal responses, electrical stimulation applied directly to these neurones was not sufficient to induce this behaviour. PMID- 1919414 TI - Early life stages of carp (Cyprinus carpio L.) depend on ambient magnesium for their development. AB - Carp eggs, fertilized in vitro, were allowed to develop in fresh water with magnesium concentrations varying from 0.001 to 0.100 mmol l-1. Magnesium concentrations below 0.010 mmol l-1 seriously impeded carp embryonic development: the incidence of deformed larvae and mortality increased steeply to 100% at water magnesium concentrations of 0.001 mmol l-1. Thus, early life stages of carp require ambient magnesium for survival and successful development. The magnesium and calcium concentrations of the developing eggs were dependent on the ambient magnesium concentration. The uptake of magnesium by eggs decreased and the uptake of calcium increased with decreasing ambient magnesium concentrations. However, the uptake of the sum of these divalent ions seemed to be independent of ambient magnesium concentration. This indicates a competition between magnesium and calcium for (passive) uptake into developing eggs. PMID- 1919415 TI - Effect of endurance swimming on the lactate kinetics of rainbow trout. AB - The lactate turnover rate of rainbow trout (Oncorhynchus mykiss) was measured by bolus injection of [U-14C]lactate at rest and during prolonged swimming at 85% Ucrit to determine the importance of this metabolic fuel for endurance locomotion in fish, to assess whether lactate exchange between white and red muscle could be a possible mechanism for supplying oxidizable fuel to their lateral red muscle, and to compare the contribution of lactate to total energy provision between teleost and mammalian species. Turnover rate only increased from 4.41 +/- 0.33 to 9.71 +/- 1.69 mumol kg-1 min-1 between rest and prolonged swimming, and the contribution of lactate oxidation to total metabolism declined during exercise. Lactate exchange between white and red muscle is, therefore, not a significant mechanism to fuel the active lateral red musculature during prolonged swimming. The lactate turnover rate of teleosts is one or two orders of magnitude lower than in mammals of equivalent size, but lactate has the same importance as a fuel in both vertebrate groups. However, lactate turnover rate and oxidation rate do not scale with body mass in the same fashion as does metabolic rate. The slope of the mammalian relationship for whole-body lactate turnover and oxidation is much lower (0.58) than the slope of the classic relationship for metabolic rate (0.75), indicating that lactate is a much more important oxidative substrate for small than for large animals. PMID- 1919416 TI - The pharmacology of cholinoceptors on the somatic muscle cells of the parasitic nematode Ascaris suum. AB - 1. Acetylcholine (ACh) elicited depolarization and an increase in input conductance of the somatic muscle cells of the parasitic nematode Ascaris suum. 2. The relative potency of nicotinic and muscarinic agents was studied in this preparation. The order of potency of these compounds was metahydroxy phenylpropyltrimethylammonium (HPPT) greater than 1.1 dimethyl-4 phenylpiperazinium (DMPP) greater than ACh greater than carbachol greater than nicotine greater than tetramethylammonium (TMA+) greater than muscarone greater than furtrethonium greater than arecoline. Decamethonium was also a weak agonist. McN-A-343 elicited a very weak depolarization at concentrations above 1 mmol l-1. Bethanechol and methacholine were without effect up to 1 mmol l-1. Pilocarpine and muscarine elicited a slight hyperpolarization of up to 3 mV with a threshold for the response of around 500 mumol l-1. Oxotremorine (1 mmol l-1) was without effect. 3. The nitromethylene insecticide 2(nitromethylene)tetrahydro 1,3 thiazine (NMTHT), an agonist at insect nicotinic receptors, was without effect on Ascaris muscle cells up to 1 mmol l-1. 4. Mecamylamine and benzoquinonium were the most potent antagonists of the acetylcholine response. The order of potency of the other antagonists was tetraphenylphosphonium (TPP) greater than quinacrine greater than pancuronium, curare greater than trimethaphan greater than atropine greater than chlorisondamine, decamethonium greater than hexamethonium greater than dihydro-beta-erythroidine. 5. The agonist profile of the Ascaris muscle cell ACh receptor clearly indicates that it is nicotinic. The potency of ganglionic and neuromuscular nicotinic receptor antagonists in Ascaris does not enable a further subclassification of this nicotinic receptor. The Ascaris nicotinic receptor seems to possess some of the pharmacological properties of each type of vertebrate nicotinic receptor. The pharmacology of the Ascaris nicotinic receptor is discussed in relation to that of nicotinic receptors in other invertebrate preparations and in vertebrate preparations. PMID- 1919417 TI - Reflex pathways responsive to depression of the locust coxotrochanteral joint. PMID- 1919419 TI - The whole-body withdrawal response of Lymnaea stagnalis. II. Activation of central motoneurones and muscles by sensory input. AB - The role of centrally located motoneurones in producing the whole-body withdrawal response of Lymnaea stagnalis (L.) was investigated. The motoneurones innervating the muscles used during whole-body withdrawal, the columellar muscle (CM) and the dorsal longitudinal muscle (DLM) were cells with a high resting potential (-60 to -70 mV) and thus a high threshold for spike initiation. In both semi-intact and isolated brain preparations these motoneurones showed very little spontaneous spike activity. When spontaneous firing was seen it could be correlated with the occurrence of two types of spontaneous excitatory postsynaptic potential (EPSP). One was a unitary EPSP that occasionally caused the initiation of single action potentials. The second was a larger-amplitude, long-duration (presumably compound) EPSP that caused the motoneurones to fire a burst of high-frequency action potentials. This second type of EPSP activity was associated with spontaneous longitudinal contractions of the body in semi-intact preparations. Tactile stimulation of the skin of Lymnaea evoked EPSPs in the CM and DLM motoneurones and in some other identified cells. These EPSPs summated and usually caused the motoneurone to fire action potentials, thus activating the withdrawal response muscles and causing longitudinal contraction of the semi-intact animal. Stimulating different areas of the body wall demonstrated that there was considerable sensory convergence on the side of the body ipsilateral to stimulation, but less on the contralateral side. Photic (light off) stimulation of the skin of Lymnaea also initiated EPSPs in CM and DLM motoneurones and in some other identified cells in the central nervous system (CNS). Cutting central nerves demonstrated that the reception of this sensory input was mediated by dermal photoreceptors distributed throughout the epidermis. The activation of the CM and DLM motoneurones by sensory input of the modalities that normally cause the whole-body withdrawal of the intact animal demonstrates that these motoneurones have the appropriate electrophysiological properties for the role of mediating whole-body withdrawal. PMID- 1919418 TI - The whole-body withdrawal response of Lymnaea stagnalis. I. Identification of central motoneurones and muscles. AB - Two muscle systems mediated the whole-body withdrawal response of Lymnaea stagnalis: the columellar muscle (CM) and the dorsal longitudinal muscle (DLM). The CM was innervated by the columellar nerves and contracted longitudinally to shorten the ventral head-foot complex and to pull the shell forward and down over the body. The DLM was innervated by the superior and inferior cervical nerves and the left and right parietal nerves. During whole-body withdrawal, the DLM contracted synchronously with the CM and shortened the dorsal head-foot longitudinally. The CM and the DLM were innervated by a network of motoneurones. The somata of these cells were located in seven ganglia of the central nervous system (CNS), but were especially concentrated in the bilaterally symmetrical A clusters of the cerebral ganglia. The CM was innervated by cells in the cerebral and pedal ganglia and the DLM by cells in the cerebral, pedal, pleural and left parietal ganglia. Individual motoneurones innervated large, but discrete, areas of muscle, which often overlapped with those innervated by other motoneurones. Motoneuronal action potentials evoked one-for-one non-facilitating excitatory junction potentials within muscle fibres. No all-or-nothing action potentials were recorded in the CM or DLM, and they did not appear to be innervated by inhibitory motoneurones. The whole network of motoneurones was electrotonically coupled, with most cells on one side of the CNS strongly coupled to each other but weakly coupled to cells on the contralateral side of the CNS. This electrotonic coupling between motoneurones is probably important in producing synchronous contraction of the CM and DLM when the animal retracts its head-foot complex during whole-body withdrawal. PMID- 1919420 TI - Coffee and cholesterol: what is brewing? PMID- 1919421 TI - The hypercholesterolaemic factor in boiled coffee is retained by a paper filter. AB - In order to study the effects of filtering on the serum cholesterol-elevating effect of boiled coffee, 20 healthy volunteers consumed, in random order, 6-10 dl d-1 of strong boiled coffee (BC) and similarly boiled coffee that had been passed through a conventional paper filter (BFC), for periods of 4 weeks in a crossover design. During periods of BC consumption serum total cholesterol and LDL cholesterol levels (P less than 0.05), as well as serum triglyceride and apoprotein B concentrations and the LDL/HDL ratio (P less than 0.01), were significantly higher than during BFC periods. Serum HDL-cholesterol and apoprotein A-I levels remained unchanged. Filtering removed more than 80% of the lipid-soluble substance that was present in boiled coffee. The results indicate that the hypercholesterolaemic factor in boiled coffee, which is presumably lipid soluble, is retained by the paper filter. They also suggest that boiling is not essential for the previously observed difference between the effects on serum lipoproteins of boiled coffee and filtered coffee. PMID- 1919422 TI - Coffee drinking and blood cholesterol--effects of brewing method, food intake and life style. AB - The strongest correlations between coffee consumption and serum cholesterol levels have been found in countries where people drink coffee brewed by mixing coffee grounds directly in boiling water (boiled coffee). In the present study of a population-based sample of 1625 middle-aged subjects (the Northern Sweden MONICA Study), approximately 50% of the participants were drinking boiled coffee, and 50% were drinking filtered coffee. Consumers of boiled coffee had significantly higher serum cholesterol levels than consumers of filtered coffee. Subjects who drank boiled coffee reported a higher intake of fat. A linear multiple regression analysis with serum cholesterol as the dependent variable confirmed that boiled coffee was an important independent determinant of cholesterol levels. We conclude that subjects who drink boiled coffee have higher serum cholesterol levels than those who drink filtered coffee, and that the most likely explanation for this finding lies in the type of brewing method. PMID- 1919423 TI - Cost-benefit analysis of non-pharmacological treatment of hypertension. AB - In this study a non-pharmacological treatment (NPT) programme and conventional drug treatment of hypertension was compared in a cost-benefit analysis. The NPT programme involved 400 patients and was conducted at 8 health centres during the period 1984-1986. It consisted of monthly visits by a nurse, visits by a doctor every 6 months, home blood pressure (BP) measurements, dietary advice, relaxation, physical activity, etc. The patients were also followed up for 2 years after the study to assess whether the programme still worked, and whether future treatment costs were affected. The treatment costs were about SEK 5300 higher per patient for the NPT programme. The benefits, in the form of reduced treatment costs for the period 1986-1988 and willingness to pay (WTP) for the NPT programme, were about SEK 3200. Thus the NPT programme resulted in a loss of about SEK 2100 per patient. However, a longer follow-up period is needed for any specific conclusions to be drawn about the costs and benefits of the NPT programme, as compared with conventional drug treatment. PMID- 1919424 TI - Serum platelet-derived growth factor and endothelin concentrations in human hypercholesterolaemia. AB - Platelet-derived growth factor (PDGF) and endothelin are both smooth muscle cell mitogens, and may have an important role in mediation of the proliferative phase of atherogenesis. Since hypercholesterolaemia is an important risk factor for atherosclerosis, we have measured serum endothelin and PDGF concentrations in matched pairs of hypercholesterolaemic patients and control subjects. Both endothelin and PDGF concentrations were higher in the hypercholesterolaemic patients (23.8 +/- 4.3 pM vs. 21.7 +/- 2.4 pM, P = 0.019, median difference 3.0, 95% confidence limits 0.6-7.3, and 115.4 +/- 60.3 pM vs. 64.7 +/- 22.7 pM P = 0.033, median difference 27.2, 95% confidence limits 1.3-82.5, respectively), while serum endothelin and PDGF concentrations were positively correlated with each other (r = 0.764, P less than 0.0001, 95% confidence limits 0.505-0.897). PDGF concentrations were correlated with the peripheral blood platelet count (r = 0.560, P = 0.007, 95% confidence limits 0.180-0.794). These findings suggest that PDGF, and possibly endothelin, may be involved in hypercholesterolaemia-related atherogenesis. PMID- 1919425 TI - Adenosine provokes myocardial ischaemia in patients with ischaemic heart disease without increasing cardiac work. AB - Intravenous infusion of adenosine in patients with ischaemic heart disease (IHD) has been shown to induce chest pain and ST-depression. The aim of this study was to determine whether such myocardial ischaemia could be due to an increase in myocardial work. Thus patients with stable angina pectoris (n = 8) were randomly allocated to exercise or adenosine infusion, with a 1-h rest period before the second test. The maximal tolerable work load was 120 +/- 13 W, where all patients but one experienced typical angina pectoris. ECG revealed ST-depressions in all patients. The maximal tolerable dose of adenosine was 108 +/- 6 micrograms kg-1 min-1. All patients experienced chest pain typical of habitual angina pectoris, and all but one developed ST-depressions. During exercise there was a gradual and marked increase in the rate pressure product (RPP), in parallel with the development of ST-depression. By contrast, during infusion of adenosine there was only a minor increase in RPP (P = 0.0001). In conclusion, infusion of adenosine provokes signs and symptoms of myocardial ischaemia in patients with IHD with only a minor increase in cardiac work compared to exercise. These results are consistent with the hypothesis of a myocardial steal. PMID- 1919426 TI - The significance of venography in the management of patients with clinically suspected pulmonary embolism. AB - The accurate diagnosis of pulmonary embolism causes many problems. Clinical signs are non-specific, and ventilation-perfusion lung scanning has high sensitivity but variable specificity. In more than 90% of cases a pulmonary embolus is derived from deep venous thrombosis in the lower extremities. We have performed a prospective study to evaluate venography in the management of patients with suspected pulmonary embolism. A total of 169 patients were included in the study, and a ventilation-perfusion scan was performed in all cases. Forty-four (26%) patients had a normal scan and treatment was not given (group A). The other 125 (74%) patients, who had an abnormal scan, underwent bilateral venography. Venous thrombosis was demonstrated in 63 patients, and they were treated with oral anticoagulants for 3 months (group B). The remaining 62 patients, who showed no venous thrombosis, did not receive anticoagulant therapy (group C). During follow up, 1 patient in group A, 3 patients in group B and 1 patient in group C developed a new deep venous thrombosis. One patient in group B suffered a pulmonary embolus. It is concluded that venography of the lower extremities can be of additional value in the management of patients with pulmonary embolism when the lung scan does not provide sufficient information. PMID- 1919427 TI - Influence of lovastatin therapy on metabolism of low density lipoproteins in mixed hyperlipidaemia. AB - To determine the mechanisms whereby HMG-CoA reductase inhibitors lower the levels of low density lipoproteins (LDL) in patients with mixed hyperlipidaemia, LDL turnover studies were conducted in 12 such patients during placebo and then during treatment with lovastatin. Drug therapy reduced total cholesterol and triglyceride concentrations by 33% and 32%, respectively. During lovastatin therapy, LDL-cholesterol levels fell by 37%, and LDL-apo B concentrations decreased by an average of 29%. The decrease in LDL-apo B concentrations on lovastatin therapy was largely due to an increase in fractional catabolic rates (FCRs) for LDL apo B. The average increase in FCRs was 34%, whereas transport rates (production rates) for LDL apo B remained unchanged. These results strongly suggest that an increase in LDL-receptor activity is the major mechanism whereby LDL levels are lowered during lovastatin therapy. The data do not indicate that this drug inhibited the input of apo B-containing lipoproteins, which would have been expected to result in a decrease in the rate of production of LDL. PMID- 1919428 TI - Severe coagulopathy after a bite from a 'harmless' snake (Rhabdophis subminiatus). AB - European physicians may occasionally be confronted with cases of snake venom poisoning. The increasing interest in snakes as pets has unfortunately resulted in the importation of a number of venomous snakes. We here report the third known case in the medical literature of a patient who was exposed to severe coagulopathy after being bitten by a 'harmless' ringsnake (Rhabdophis subminiatus). The prolonged bleeding diathesis and the complete depletion of fibrinogen observed in our patient are consistent with the presence of a factor X activator in the venom, as has been described in a murine model. In agreement with the two previous case reports, we found no evidence of severe organ damage, despite active intravascular coagulation. PMID- 1919429 TI - Extra-adrenal phaeochromocytoma presenting as fulminant malignant disease with tumour positive sputum cytology. AB - A case of a 69-year-old man with an extra-adrenal malignant phaeochromocytoma is described. Sputum cytology revealed metastatic cells, which have not been reported previously in malignant phaeochromocytoma. This case is also remarkable for the short duration of disease, rapid progression and extensive spread of metastases, the radiological aspect of metastatic lesions shown by chest X-ray, hypercalcaemia and extremely high levels of circulating catecholamines and urinary metabolites. PMID- 1919430 TI - Multiple myeloma and chronic myelomonocytic leukaemia developing in a patient with autoimmune disease. AB - A 64-year-old lady with a personal and family history of autoimmune disease developed chronic myelomonocytic leukaemia and multiple myeloma simultaneously. Her sister died of acute myelomonocytic leukaemia, but showed no evidence of autoimmune disease. It is possible that chronic immunological stimulation, perhaps by an autoantigen, may predispose toward malignant transformation in both plasma cell and monocyte series. However, the present observations raise the alternative possibility of a primary disorder of monocytes that predisposes toward both autoimmune disease and a clonal disorder of plasma cells. PMID- 1919431 TI - Microdialysis--a new and promising method in clinical medicine. PMID- 1919432 TI - Microdialysis--principles and applications for studies in animals and man. AB - Microdialysis is a technique for sampling the chemistry of the individual tissues and organs of the body, and is applicable to both animal and human studies. The basic principle is to mimic the function of a capillary blood vessel by perfusing a thin dialysis tube implanted into the tissue with a physiological liquid. The perfusate is analysed chemically and reflects the composition of the extracellular fluid with time due to the diffusion of substances back and forth over the membrane. Microdialysis is thus a technique whereby substances may be both recovered from and supplied to a tissue. The most important features of microdialysis are as follows: it samples the extracellular fluid, which is the origin of all blood chemistry; it samples continuously for hours or days without withdrawing blood; and it purifies the sample and simplifies chemical analysis by excluding large molecules from the perfusate. However, the latter feature renders the technique unsuitable for sampling large molecules such as proteins. The technique has been extensively used in the neurosciences to monitor neurotransmitter release, and is now finding application in monitoring of the chemistry of peripheral tissues in both animal and human studies. PMID- 1919433 TI - Microdialysis sampling of the neuronal environment in basic and clinical research. AB - Microdialysis is a technique for sampling extracellular fluid (ECF) which has been employed in brain research for about 10 years, and is now in experimental and clinical use in a number of biomedical disciplines. We report on microdialysis of neuroactive amino acids in the central nervous system (CNS) and discuss some technical problems of microdialysis, such as tissue reactions, calibration and the difficulties involved, as well as strategies for determination of the true extracellular concentration of various compounds. Possible mechanisms of nerve cell death in ischaemia and hypoglycaemia are among the factors that have been elucidated using data obtained by microdialysis. The neuronal environment overflows with excitatory amino acids both in brain ischaemia and in hypoglycaemia. PMID- 1919434 TI - Microdialysis of adipose tissue. AB - Although microdialysis has been available for almost two decades, it has only recently been applied in investigations of adipose tissue. The microdialysis technique enables continuous sampling of metabolites and other small molecules from the extracellular space of subcutaneous adipose tissue from intact animals or man, and the exposure of this compartment locally to metabolically active agents without causing generalized effects. To date, the method has been used to measure the steady-state interstitial levels of metabolites and to investigate the regulation of lipolysis and carbohydrate metabolism in situ in subcutaneous adipose tissue. Apart from a great potential for experimental research, the microdialysis method offers several new possibilities for clinical investigation. Because microdialysis probes are easy to implant and cause little discomfort, they may be used for continuous monitoring of glucose and glycerol (lipolysis index) in the treatment of diabetes, obesity and other disorders characterized by disturbances in lipid and carbohydrate metabolism. PMID- 1919435 TI - Defective intracellular transport as a common mechanism limiting expression of inappropriately paired class II major histocompatibility complex alpha/beta chains. AB - Distinct combinations of class II major histocompatibility complex (MHC) alpha and beta chains show widely varying efficiencies of cell surface expression in transfected cells. Previous studies have analyzed the regions of the class II chains that are critically involved in this phenomenon of variable expression and have shown a predominant effect of the NH2-terminal domains comprising the peptide-binding site. The present experiments attempt to identify the post translational defects responsible for this variation in surface class II molecule expression for both interisotypic alpha/beta combinations failing to give rise to any detectable cell membrane molecules (e.g., E alpha A beta k) and intraisotypic pairs with inefficient surface expression (e.g., A alpha d A beta k). The results of metabolic labeling and immunoprecipitation experiments using L cell transfectants demonstrate that in both of these cases, the alpha and beta chains form substantial amounts of stable intracellular dimers. However, the isotype- and allele-mismatched combinations do not show the typical post-translational increases in molecular weight that accompany maturation of the N-linked glycans of class II MHC molecules. Studies with endoglycosidase H reveal that no or little progression to endoglycosidase H resistance occurs for these mismatched dimers. These data are consistent with active or passive retention of relatively stable and long-lived mismatched dimers in a pre-medial-Golgi compartment, possibly in the endoplasmic reticulum itself. This retention accounts for the absent or poor surface expression of these alpha/beta combinations, and suggests that conformational effects of the mismatching in the NH2-terminal domain results in a failure of class II molecules to undergo efficient intracellular transport. PMID- 1919436 TI - Rapid and specific conversion of precursor interleukin 1 beta (IL-1 beta) to an active IL-1 species by human mast cell chymase. AB - Secretory granules of human dermal mast cells contain a chymotrypsin-like serine proteinase called chymase. In this study, we demonstrate that the inactive cytokine, 31 kD interleukin 1 beta (IL-1 beta), can be converted rapidly to an 18 kD biologically active species by human mast cell chymase. The product formed is three amino acids longer at the amino terminus than the mature IL-1 beta produced by peripheral blood mononuclear cells and has comparable biological activity. Because chymase is a secretory granule constituent, it is likely to be released into the surrounding tissue when mast cells degranulate. It is also known that non-bone marrow derived cells resident in skin (keratinocytes, fibroblasts) produce but do not process 31 kD IL-1 beta. In this context, chymase may be a potent activator of locally produced 31 kD IL-1 beta. Mast cells lie in close apposition to blood vessels in dermis; therefore, chymase mediated conversion of 31 kD IL-1 beta might be expected to have a critical role in the initiation of the inflammatory response in skin. PMID- 1919437 TI - Macrosialin, a macrophage-restricted membrane sialoprotein differentially glycosylated in response to inflammatory stimuli. AB - Rat monoclonal antibody FA/11 has been used to identify macrosialin, a sialoglycoprotein confined to murine mononuclear phagocytes and related cells. Originally identified as a macrophage-associated glycoprotein predominantly localized in intracellular membranes (Smith, M.J., and G.L.E. Koch. 1987. J. Cell Sci. 87:113), the antigen is widely expressed on tissue macrophages, including those in lymphoid areas, and is expressed at low levels on isolated dendritic cells. Immuno-adsorption experiments reported here show that macrosialin is identical to the major 87-115-kD sialoglycoprotein previously identified by lectin blotting in exudate but not resident peritoneal macrophages (Rabinowitz, S., and S. Gordon. 1989. J. Cell Sci. 93:623). Resident peritoneal macrophages express low levels of macrosialin antigen in a glycoform that does not bind 125I wheat germ agglutinin or 125I peanut agglutinin; inflammatory stimuli upregulate expression of this antigen (up to 17-fold), in an alternative glycoform that is detected by these lectins. Pulse-chase experiments reveal a 44-kD core peptide that initially bears high-mannose chains (giving Mr 66 kD) and is subsequently processed to a mature protein of Mr 87-104 kD. Each glycoform contains N-linked glycan, as well as O-linked sugar structures that show alternative processing. Poly-N-acetyllactosamine structures are detected in the exudate cell glycoform only. This new marker for mononuclear phagocytes illustrates two strategies by which macrophages remodel their membranes in response to inflammatory stimuli. Its predominantly intracellular location and restricted cell distribution suggest a possible role in membrane fusion or antigen processing. PMID- 1919438 TI - Regulation of the immune response to peptide antigens: differential induction of immediate-type hypersensitivity and T cell proliferation due to changes in either peptide structure or major histocompatibility complex haplotype. AB - The immunodominant CD4 T cell epitope of the bacteriophage lambda cI repressor protein in several inbred mouse strains can be represented by a peptide encompassing amino acids 12-26. Here, we show that this peptide, and a variety of its sequence variants, can induce immediate-type hypersensitivity in mice. 12-26 variants that differ by as little as single amino acid residues deviate greatly in their ability to induce hypersensitivity. Further, differences in major histocompatibility complex class II alleles appear to be as influential as changes in peptide structure in determining whether hypersensitivity is developed. The ability of a given peptide-class II combination to induce hypersensitivity correlates with production of peptide-specific antibody, but not with ability or inability to induce a T cell proliferative response. Administration of anti-interleukin 4 (IL-4) mAb prevents the development of hypersensitivity, and analysis of cytokine production by T cell hybridomas derived from peptide-immunized mice suggests that whether a given peptide-class II combination can induce hypersensitivity depends on its ability to induce IL-4 production. The data demonstrate that changes in the nature of the epitope(s) recognized by the CD4 T cell population can result in qualitative differences in the response elicited in this population, ultimately leading to dramatic quantitative and qualitative variations in the effector phase of the immune response. PMID- 1919439 TI - Distinct effects of two CD44 isoforms on tumor growth in vivo. AB - Tumor growth is dependent in part on interactions between tumor cells and the extracellular matrix of host tissues. Expression of the cell surface glycoprotein CD44/Pgp-1, which mediates cell-substrate interactions is increased in many types of malignancies, but the role of CD44 in tumor growth is largely undefined. Recently, two isoforms of CD44 have been identified: an 80-90 kD form, which has high affinity for cell bound hyaluronate and a 150 kD form which does not mediate attachment to hyaluronate-coated surfaces. In this work, human B cell lymphoma cells stably transfected with cDNA clones encoding either of the two CD44 isoforms were compared for tumorigenicity and metastatic potential in nude mice. Expression of the 80-90 kD form but not the 150 kD form of CD44 greatly enhanced both local tumor formation and metastatic proclivity of the lymphoma cells. Our results suggest that CD44 polypeptides may play an important role in regulating primary and metastatic tumor development in vivo. PMID- 1919440 TI - Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells. AB - Transgenic mice homozygous for a beta 2-microglobulin (beta 2-m) gene disruption and normal mice that had been treated with a CD8-specific mAb were infected intranasally with an H3N2 influenza A virus. Both groups of CD8T cell-deficient mice eliminated the virus from the infected respiratory tract. Potent CTL activity was detected in lung lavage populations taken from mice with intact CD8+ T cell function, with minimal levels of cytotoxicity being found for inflammatory cells obtained from the antibody-treated and beta 2-m mutant mice. We therefore conclude that cells infected with an influenza A virus can be cleared from the respiratory tract of mice lacking both functional class I major histocompatibility complex (MHC) glycoproteins and class I MHC-restricted, CD8+ effector T cells. PMID- 1919441 TI - Ammonium chloride, an inhibitor of phagosome-lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic mycobacterium and a nonpathogenic yeast. AB - The weak base ammonium chloride has been previously reported to inhibit lysosomal movements and phagosome-lysosome (Ph-L) fusion in cultured mouse macrophages (M phi), thus reducing delivery, to an intraphagosomal infection, of endocytosed solutes that have concentrated in secondary lysosomes. We have now addressed the question, whether NH4Cl might affect any direct interaction (if it exists) between such infection phagosomes and earlier, nonlysosomal compartments of the endocytic pathway, i.e., solute-containing endosomes. The phagosomes studied were formed after ingestion of the mouse pathogen Mycobacterium microti and the nonpathogenic yeast Saccharomyces cerevisiae; and the endosomes were formed after nonreceptor-mediated endocytosis of electronopaque and fluorescent soluble markers. By electron microscopy, survey of the cell profiles of M phi that had been treated with 10 mM NH4Cl so that Ph-L fusion was prevented, and that displayed many ferritin-labeled endosomes, revealed numerous examples of the fusion of electronlucent endosomes, revealed numerous examples of the fusion of electronlucent vesicles with phagosomes, whether containing M. microti bacilli or S. cerevisiae yeasts. Fusion was recognized by transfer of label and by morphological evidence of fusion in progress. The fusing vesicles were classed as endosomes, not NH4Cl-lysosomes, by their appearance and provenance, and because lysosome participation was excluded by the concurrent, NH4Cl-caused block of Ph-L fusion and associated lysosomal stasis. No evidence of such phagosome-endosome (Ph-E) fusion was observed in profiles from M phi treated with chloroquine, nor in those from normal, untreated M phi. NH4Cl-treated living M phi that had ingested yeasts at 37 degrees C, followed by endocytosis of lucifer yellow at 17 degrees C (to accumulate labeled endosomes and postpone label passing to lysosomes), were then restored to 37 degrees C. Fluorescence microscopy showed that as many as half of the yeast phagosomes (previously unlabeled) rapidly became colored. We inferred that this transfer was from endosomes (by Ph-E fusion) because Ph-L passage was blocked (by the NH4Cl). We conclude that NH4Cl induces Ph-E fusion at the same time as it suppressed Ph-L fusion. We discuss the mechanisms of these concurrent effects and suggest that they are independent; and we consider the implications of NH4Cl opening a direct route for endocytosed molecules to reach an intraphagosomal infection without involving lysosomes. PMID- 1919442 TI - Specialized functions of major histocompatibility complex class I molecules. II. Hmt binds N-formylated peptides of mitochondrial and prokaryotic origin. AB - The physiological functions of the mouse telomeric major histocompatibility complex (MHC) class I molecules, including Hmt, are unknown. Hmt presents a polymorphic, N-formylated peptide encoded by the mitochondrial gene ND1 forming the cell surface maternally transmitted antigen (Mta). Because the N-formyl moiety is required for Hmt binding, we proposed that Hmt may function generally in presentation of N-formylated antigens. This hypothesis was validated by a competitive binding assay, demonstrating that synthetic N-formyl peptides from other mitochondrial genes also bound Hmt. Bacteria similarly initiate protein synthesis with N-formylmethionine; indeed, we established that Hmt can also present prokaryotic peptides in an N-formyl-dependent manner. These results indicate biochemical specialization of this MHC-peptide interaction and suggest a unique role for Hmt in prokaryotic host defenses. PMID- 1919443 TI - Exogenous peptides compete for the presentation of endogenous antigens to major histocompatibility complex class II-restricted T cells. AB - Antigen-presenting cells (APC) transfected with a construct encoding the hen egg white lysozyme (HEL) amino acid sequence 1-80 constitutively present HEL peptides complexed to major histocompatibility complex (MHC) class II molecules to specific T cell hybridomas, indicating that endogenous cellular antigens can be efficiently presented to class II-restricted T cells. Here we show that exogenous peptide competitors added to HEL-transfected APC can inhibit the presentation of endogenous HEL peptides to class II-restricted T cells. The inhibition is specific for the class II molecule binding the competitor peptide, and it affects to the same extent presentation of exogenous or endogenous HEL peptides. These results, demonstrating that an exogenous competitor can inhibit class II restricted T cell activation induced by endogenous as well as exogenous antigen, suggest lack of strict compartmentalization between endogenous and exogenous pathways of antigen presentation. Since autoreactive T cells may recognize endogenous, as well as exogenous antigens, the results have implications for the treatment of autoimmune diseases by MHC blockade. PMID- 1919445 TI - Abortion attitudes. PMID- 1919444 TI - The lymphocyte glycoprotein CD6 contains a repeated domain structure characteristic of a new family of cell surface and secreted proteins. AB - The isolation, characterization, and expression of a full-length cDNA encoding the human T cell glycoprotein CD6 is described. COS cells transfected with the CD6 clone express a 90-kD protein that reacts with all available anti-CD6 monoclonal antibodies. RNA blot hybridization analysis indicates that CD6 transcripts are predominantly restricted to cells in the T lineage. The predicted CD6 sequence is 468 amino acids long, with the typical features of a type I integral membrane protein. The cytoplasmic domain of CD6 contains two serine residues, one or both of which are substrates for phosphorylation during T cell activation. The extracellular domain of CD6 is significantly related to the extracellular domain of the human and mouse T cell antigen CD5, the cysteine-rich domain of the bovine and mouse type I macrophage scavenger receptor, the extracellular domain of the sea urchin spermatozoa protein that crosslinks the egg peptide speract, the mammalian complement factor 1, and the human lung tumor antigen L3. These molecules, therefore, constitute a new gene superfamily that is well conserved across species boundaries. PMID- 1919446 TI - Shoulder dystocia. PMID- 1919447 TI - Drug interaction. PMID- 1919449 TI - Personal perspectives on collecting Papanicolaou smears or how I learned to use the stirrups. PMID- 1919448 TI - Diabetes care: what should we try to achieve? PMID- 1919450 TI - Type II diabetic subjects with secondary failure: treatment with prebreakfast mixed ultralente and regular insulin with a sulfonylurea. AB - BACKGROUND: Combination therapy with sulfonylurea and insulin is reported to be effective in several recent reports on the management of non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea. Most of these studies used insulin twice daily, however, and hence failed to offer a significant practical advantage over insulin therapy alone. Since a subcutaneous injection of Ultralente insulin exerts its peak effect between 16 and 18 hours after injection, its prebreakfast administration is likely to inhibit overnight hepatic glucose production, which is a primary modulator of fasting plasma glucose, a major determinant of diurnal glycemia in NIDDM: Moreover, the simultaneous administration of regular insulin tends to improve glycemia during the premeal and immediate postmeal period before the onset of sulfonylurea induced insulin secretion. METHODS: We assessed the efficacy of a prebreakfast subcutaneous injection of mixed Ultralente and regular insulin in conjunction with prior sulfonylurea therapy in 20 NIDDM subjects after precise documentation of secondary failure to these agents initially for the period of 3 months, followed by a long-term evaluation for up to 2 years. RESULTS: Metabolic control improved significantly as reflected by a decline in fasting plasma glucose (FPG) and HbA1c concentrations (FPG, 14.4 mmol/L +/- 0.4 vs 79 mmol/L +/- 0.3 mM/L; HbA1c, 11.7% +/- 0.3% vs 8.8% +/- 0.1%; P less than .001 for both comparisons). Serum cholesterol and triglycerides decreased as well, although the change was significant for triglycerides alone. Body weights and blood pressure remained unaltered. Furthermore, metabolic control appeared to remain in the same range during the long-term follow-up period. CONCLUSIONS: Adjuvant therapy with sulfonylurea and a single prebreakfast subcutaneous injection of mixed Ultralente and regular insulin may be an effective and practical therapeutic option in the management of NIDDM with secondary failure to sulfonylurea. PMID- 1919451 TI - Clinical significance of hyperkeratosis on otherwise normal Papanicolaou smears. AB - BACKGROUND: Although hyperkeratosis is a common cytological finding on Papanicolaou smear, its clinical significance is unclear. METHODS: A profile of patients with hyperkeratosis was constructed by comparing them to an age-matched control population having normal Papanicolaou smears. The clinical significance of hyperkeratosis was evaluated and appropriate follow-up studies were recommended. RESULTS: Of 2198 Papanicolaou smears done in the University of Kansas Family Practice Department between October 1, 1988, and October 31, 1989, there were 184 diagnoses of hyperkeratosis from smears on which no other pathological findings were noted. Charts of 183 of these patients with hyperkeratosis were reviewed and compared with an age-matched control population having normal Papanicolaou smears. Patients with hyperkeratosis had a statistically higher incidence of infections with Gardnerella vaginalis, but a lower incidence of infections with Chlamydia trachomatis. Diaphragm use was more prevalent in the group with hyperkeratosis. The incidence of inflammation on Papanicolaou smear was similar between the two groups. Of the patients with hyperkeratosis, colposcopic examination had been performed on 48% (88 of 183), of which 28% (25 of 88) had evidence of human papillomavirus or dysplasia. CONCLUSIONS: Review of the data obtained suggests that follow-up colposcopy, including endocervical curettage, be performed on all patients with hyperkeratosis in order to screen for accompanying pathological conditions that may necessitate treatment. PMID- 1919453 TI - Prevalence and prediction of chlamydial cervical infection in a rural area: an UPRNet project. AB - BACKGROUND: Though many studies have described the prevalence of genital Chlamydia trachomatis infections in urban and suburban populations, no data on a rural general practice population have been published. Knowledge of the prevalence of infection is necessary to develop screening strategies. METHODS: The Upper Peninsula Research Network (UPRNet) is a rural primary care research group composed of five family practice offices. Cervical cultures for C trachomatis were taken on all women under the age of 36 years who presented to UPRNet physicians for a pelvic examination for any reason between August 15 and November 10, 1989. Demographic and clinical variables were analyzed for correlation with infection, and the best predictors of infection were identified by logistic regression. Previously published screening protocols were then tested on our data to develop the best predictive model for our rural population. RESULTS: C trachomatis was cultured from 25 (4.7%, 95% CI 2.9% to 6.5%) of 530 consecutive women. Infection was significantly more common among younger and single women, women with a new sex partner, and women with mucopurulent cervical discharge or increased cervical friability. No symptoms were predictive of an increased risk of infection. Based on the clinical presentation alone, the physicians correctly predicted only 28% of the infections. Using a modified Rosenthal protocol, we would have identified 80% of the infections while testing only 31% of the women. The protocols of Magder and Handsfield and their respective colleagues performed reasonably well, too. Other published screening protocols were less useful. CONCLUSIONS: The prevalence of C trachomatis cervical infection in our rural primary care office population is relatively low. In rural primary care we recommend testing all high-risk women using a modification of Rosenthal's protocol instead of relying on symptoms or clinical suspicion. PMID- 1919452 TI - Effect of continuing medical education and cost reduction on physician compliance with mammography screening guidelines. AB - BACKGROUND: Primary care physicians perform breast cancer screening in women aged 50 years and older less frequently than recommended by national guidelines. METHODS: A multimethod continuing medical education (CME) intervention was tested in an attempt to increase breast cancer screening practices in a predominantly fee-for-service practice community in New York State. Preintervention and postintervention surveys of primary care physicians were conducted in 1988 and 1990, respectively. Project-initiated, low-cost mammography in one town and the unanticipated provision of free mammography services in another town under nonproject auspices permitted a comparison to be made between these towns and towns where mammography screening was provided at the prevailing fees to determine the impact that cost has on physicians' referral of women patients for mammography. RESULTS: Physicians practicing in the towns in which the CME intervention was provided showed a significant increase, consistent across specialty groups and greatest among family physicians, in the number of reported mammography referrals of asymptomatic women aged 50 to 75 years. Changes in the CME control town were smaller and not statistically significant for the sample size available. The increase in compliance was as large in the CME-intervention towns, one without (19%) and one with low-cost mammography (20%), as the increase in the town with free mammography alone (18%). There were no significant increases in reported performance of breast examination. CONCLUSIONS: A multimethod program of CME is a feasible approach to increasing community physician compliance with mammography screening guidelines, particularly among family physicians, and can enhance the impact of reduced cost or have at least the equivalent effect of free mammography services. PMID- 1919454 TI - Experiences of family members after a suicide. AB - BACKGROUND: Survivors of suicide are the family members and significant others in the life of the person who commits suicide. A recent study by the author explored the life experiences of survivors of suicide, affirmed the severity of postsuicide bereavement, and revealed the critical role of the family physician in intervention. METHODS: Thirty-five adult survivors participated in in-depth audiotaped interviews during the 3- to 9-month period after the suicide death of a family member. Demographic data and the transcribed interview data were analyzed through descriptive statistics and systematic methods of qualitative data analysis. RESULTS: Subjects stressed the importance of the family physician understanding the nature of their experiences in order to intervene effectively. All survivors experienced profound disruptions in their lives, including changes in physical, emotional, cognitive, and social functioning. Variations among survivors of suicide, based on the survivor's perception of the victim before his or her death, were evident and are illustrated by three case studies. Interventions for the family physician, including specific suggestions from survivors, are proposed. CONCLUSIONS: Survivors of suicide experience a very severe bereavement, yet significant variations exist among their responses. The family physician is identified as the key individual to initiate and ensure follow-up care for this bereaved population. PMID- 1919455 TI - Accuracy of papilledema and pseudopapilledema detection: a multispecialty study. AB - BACKGROUND: Present trends in medical care suggest that primary care physicians will exert increasing control over patient access to medical specialty consultation and diagnostic testing. Therefore, it is important to determine whether primary care physicians can reliably identify papilledema. METHODS: A prospective study involving 429 physicians was undertaken to assess the accuracy of papilledema and pseudopapilledema detection by five groups of physicians, family practice physicians, neurologists, neuro-ophthalmologists, neurosurgeons, and ophthalmologists. RESULTS: Neuro-ophthalmologists and ophthalmologists did better than family physicians, neurologists, and neurosurgeons in identifying both papilledema and pseudopapilledema (P less than .05). Neuro-ophthalmologists more accurately identified pseudopapilledema than all other groups in the study (P less than .05). Family physicians did as well as, or better than, neurologists and neurosurgeons in identifying all classifications of acute and chronic papilledema defined in the study. Family physicians did not perform as well as the other four groups in differentiating pseudopapilledema from papilledema (P less than .05). CONCLUSIONS: Although the sensitivity of detecting papilledema was high (84.5%) for family physicians, the specificity was low (59.3%). Preliminary data indicate that family physicians with prior exposure to clinical ophthalmology in medical school did better than those who had not had training. It is possible that additional exposure to clinical ophthalmology during residency training might yield improved performance. PMID- 1919456 TI - Liability insurance for moonlighting by family practice residents. AB - BACKGROUND: Moonlighting is a widespread practice among residents in family practice programs. It is thought that many residents fail to appreciate the problems that moonlighting may pose with respect to liability insurance. METHODS: A survey regarding liability insurance instruction and moonlighting insurance was sent to the chief resident of each family practice residency program (380) in the United States. An overall response rate of 78.7% was achieved. RESULTS: Chief residents appear to have limited knowledge about liability insurance, believe that education about liability insurance in the residency program is inadequate, and are not well informed regarding liability insurance issues related to moonlighting. CONCLUSIONS: Information regarding professional liability insurance and its implications for the resident who chooses to moonlight should be a part of the practice management curriculum of every residency program. PMID- 1919457 TI - Use of a computer-based health risk appraisal by older adults. AB - BACKGROUND: A health risk appraisal (HRA) is a tool for health promotion. Conversational microcomputer-based HRAs may be more cost effective than other HRA formats. The acceptability of conversational HRAs, however, has not been demonstrated for older adults. METHODS: We studied the acceptability of a conversational microcomputer-based HRA in a sample of 247 adults at the Minnesota State Fair and the Senior Options Exposition. All users were offered the appraisal via mouse or keyboard interface. Acceptability was measured in terms of user-reported helpfulness, intent to change, time of use, and willingness to view HRA health recommendations. Data on completion time and willingness to view HRA recommendations were collected for Senior Exposition users only. Regression analyses were used to examine the combined impact of interface (mouse or keyboard), location (State Fair or Senior Exposition), age, and sex on user acceptability. Results. Interface and location had no effect on helpfulness or change ratings. Older users rated the appraisal more helpful (P less than .007). Both older and female users reported more intent to change behavior (P = .016, both). Time to use the appraisal was related to interface, age, and sex. Mouse users (P less than .0001), older users (P less than .0001) and female users (P less than .05) took significantly longer to use the appraisal. Significantly more mouse users declined to see recommendations (P less than .02). CONCLUSIONS: Older users can derive as much or more value from conversational health risk appraisals as younger users; however, a mouse interface may be less effective for this age group. PMID- 1919458 TI - Board certification and practice style: an analysis of office-based care. AB - BACKGROUND: The relationship between family practice certification and practice style has important health policy implications. We used data from the RAND Health Insurance Experiment to study the relationship between family practice certification and (1) patient characteristics including age and sex of patients, and (2) facets of practice style including probability of hospital admission, number of visits in an episode of care, number of physicians seen per episode, total charges per episode, charges per service category, and inputs per service category. METHODS: Data on health care service utilization by a sample of 5554 nonelderly individuals over a 1-year period were used to define episodes of care. Multivariate regression techniques were used to measure the association between family practice certification and patient characteristics and between family practice certification and practice style, controlling for the effects of patients characteristics. RESULTS: Patients of certified family physicians were an average of 3 years younger than patients of noncertified family physicians, but other demographic characteristics were similar. Certified family physicians had higher pathology services charges and inputs, but no statistically significant differences in other measures of charges and inputs. CONCLUSIONS: Certified and noncertified family physicians treat similar patients. Certification in family practice is not associated with major differences in total service charges, but is associated with differences in the use of laboratory diagnostic services. PMID- 1919459 TI - Fire ants: the death march. PMID- 1919460 TI - The scope of research in family practice and primary care. PMID- 1919461 TI - Protective effects of manganese, cobalt, nickel, and barium against a calcium paradox in the isolated frog heart. AB - The effect of inorganic slow channel blockers on the calcium paradox in the frog heart was examined. Addition of the divalent cations of manganese, cobalt, nickel, or barium during calcium depletion protected the frog heart against a calcium paradox. This protective effect was indicated by reduced protein release, maintenance of electrical activity, and recovery of mechanical activity during reperfusion. Tissue calcium determination results showed that in the control paradox in the absence of divalent cations, there is an efflux of calcium from myocardial cells during calcium depletion and a massive influx of calcium during the following reperfusion, leading to a calcium overload. Divalent cations protected frog myocardial cells, when present in the calcium-free perfusion medium, by reducing both calcium efflux during calcium depletion and the massive calcium influx during reperfusion. The effectiveness of the added divalent cations showed a strong dependence upon their ionic radius. The most potent inhibitors of the calcium paradox in the frog heart were the divalent cations having an ionic radius closer to the ionic radius of calcium. These results are discussed in terms of the possible mechanism involved in the protective effect of manganese, cobalt, nickel, and barium. PMID- 1919462 TI - Subdivisions of the terminal nerve in Xenopus laevis. AB - The majority of recent studies on the terminal nerve (nt) in various vertebrates either involved tracer injections into the nasal cavity or made use of the LHRH /FMRFamide-like immunoreactivity (ir) of a portion of its fibers. The present investigation was designed to determine the extent of overlap between data rendered by the two methods in Xenopus. The findings reveal no overlap of nt projections visualized by the two experimental techniques. This result sheds doubt on the validity of current definitions of the nt system. PMID- 1919464 TI - Cleavage rates of diploid and tetraploid mouse embryos during the preimplantation period. AB - Despite the fact that spontaneous tetraploidy is a rare phenomenon in mice, such embryos may be produced experimentally by a variety of means, though only a very limited degree of postimplantation development has been achieved. Despite this apparent limitation, much data on the rate of development of preimplantation tetraploid embryos has been published. However, the findings from these studies has often been conflicting. In the light of the recent successful achievement of advanced postimplantation tetraploid development in our laboratory, we decided it was an opportune time to re-evaluate the preimplantation development of these embryos in as near to optimal conditions as we could achieve. Three groups were studied, namely 1) control (diploid) embryos developing in vivo, 2) control (diploid) embryos that had been isolated at the 2-cell stage, briefly retained in culture, then transferred to the oviducts of pseudopregnant recipients, and 3) tetraploid embryos produced by electrofusion of blastomeres at the 2-cell stage, then transferred to the oviducts of pseudopregnant recipients. Embryos were isolated from females from each group at specific times after the HCG injection to induce ovulation. The total cell number of each embryo was established and the log mean values were plotted against time. From the gradients of the lines it was possible to establish that there was a significant difference between the cell doubling time of the transferred controls (group 2) compared to the in vivo controls (group 1) with cell doubling times of 15.86 +/- 1.45 h and 10.27 +/- 0.24 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919463 TI - Sex differences in hepatic monooxygenases in winter flounder (Pseudopleuronectes americanus) and scup (Stenotomus chrysops) and regulation of P450 forms by estradiol. AB - Details concerning the endogenous regulation of hepatic cytochrome P450 monooxygenases in teleosts, and the features of this regulation common among fish species, are poorly known. Gonadally mature female winter flounder (Pseudopleuronectes americanus) have been reported to have severalfold lower levels of microsomal cytochromes P450 and b5 and NADPH-cytochrome c reductase than do males (Stegeman and Woodin ('84) Mar. Environ. Res., 14:422-425). These strong sex differences prompted more detailed study of P450 regulation in winter flounder liver, and a comparison with sex differences in another marine teleost, scup (Stenotomus chrysops). Ethoxyresorufin O-deethylase (EROD) activity/nmol P450 was less in gonadally mature females than in males of both species. Immunoblot analysis with MAb 1-12-3 to P450E (the EROD catalyst) showed that the content of P450E counterpart was also much less in females of both species. Aminopyrine N-demethylase (APND) and testosterone 6 beta-hydroxylase (6 beta OHase) activities per nmol P450 were higher in gonadally mature female than in mature male flounder, differences not seen in scup. Polyclonal antibodies to scup P450A were shown to detect proteins in a number of teleosts. The levels of anti P450A cross-reacting protein were greater in mature female than in male flounder, but as with 6 beta-OHase activity, the content of this protein was not sexually differentiated in scup. Estradiol treatment of winter flounder depressed the rates of EROD, APND, 6 beta-OHase, and estradiol 2-OHase activities per mg protein, but APND and 6 beta-OHase activities per nmol P450 were unchanged. Thus, E2 promotes general decreases in some hepatic P450-catalyzed activities, but in achieving sex differences there is also specific regulation of the P450E counterpart, and possibly of the 6 beta-OHase (P450A?). Other factors, temporal or hormonal, can modify the effect of E2 treatment, and may contribute to the specific regulation of P450 forms in naturally maturing fish, and to species differences in this regulation. PMID- 1919465 TI - Zinc-protein from rat prostate fluid binds epididymal spermatozoa. AB - The detection and the isolation of a zinc-protein from the secretion of the rat dorsolateral prostate is described. The purification procedure, based on gel filtration and cationic exchange chromatography, allowed to separate a minor protein (Mr approximately 66,000) from free zinc ions and other secretory components. Two zinc ions were estimated to be associated with one molecule of isolated protein. The zinc-protein was labelled with 125I and then incubated at 37 degrees C with spermatozoa from rat epididymal cauda. Time-dependent in vitro binding of the radioactive protein to sperm cells was demonstrated. This binding was not affected by the presence of proteins from the seminal vesicle during the incubation, while it was blocked in the presence of an excess of unlabelled zinc protein. After binding, the labelled spermatozoa were treated with a buffer containing 0.5% sodium deoxycholate and 40 mM EDTA; only very small amounts of label were removed from the cells, thus suggesting that the zinc-proteins were kept on the plasma membrane by interactions which do not involve merely hydrophobic bonds. PMID- 1919466 TI - Resumption of meiosis in pig oocytes cultured with cumulus and parietal granulosa cells: the effect of protein synthesis inhibition. AB - In denuded and cumulus-enclosed pig oocytes, puromycin at concentrations 5, 10, and 25 micrograms/ml did not lower the rate of germinal vesicle breakdown (GVBD) after 24 h of culture. GVBD was prevented in 50, 75, and 100 micrograms/ml of puromycin. After 40 h of culture, 5 and 10 micrograms puromycin/ml impaired significantly incidence of metaphase II (42 and 30%), respectively. Concentrations of 25 and 50 micrograms puromycin/ml absolutely prevented the first polar body (I PB) expulsion. The results indicated that GVBD in pig oocytes is far less sensitive to puromycin than I PB expulsion. Culture of cumulus enclosed pig oocytes isolated with a piece of membrana granulosa (C + P oocytes) did not allow GVBD after 24 and 32 h in control medium. After 24 h of culture, GVBD occurred in 43 and 56% of C + P oocytes in the medium supplemented with 17 and 25 micrograms puromycin/ml. GV was broken down in 80 and 68% of C + P oocytes cultured in 17 and 25 micrograms puromycin/ml for 32 h. It is concluded that inhibition of protein synthesis by puromycin released pig oocytes from the block exerted by granulosa cells. PMID- 1919468 TI - Statistical evaluation of the evidential value of human hairs possibly coming from multiple sources. AB - A concept of the mathematical evaluation of human hair evidence is derived. This concept can be realized in a special computer program, the output of which is an incrimination probability. The problems of not knowing the true number of sources and the correct partition of hairs corresponding to their sources are solved from the point of view of avoiding an unjustified incrimination. PMID- 1919467 TI - Oocyte and zygote zona pellucida lectin binding in BALB/cBy and C57BL/6By mice and their F1 hybrids. AB - Zona pellucida intact oocytes and zygotes from two inbred strains of mice (BALB/cByEss and C57BL/6ByEss) and their F1 hybrids were reacted with a lectin panel (ConA, WGA, sWGA, PNA, UEA I, LTA, BSB4, DBA, PHA-P, LPA, and LFA). No major differences were observed between groups of mice for the majority of the lectin binding patterns. However, oocytes from BALB/cByEss and the F1 (C57BL/6ByxBALB/cBy) gave identical binding patterns for PNA. Following fertilization BALB/cByEss and the F1 (C57BL/6ByxBALB/cBy) bound UEAI and LTA more strongly, but the other two groups of mice demonstrated identical weaker binding of UEAI and LTA. These results indicate the possible influence of the paternal genotype on zona pellucida formation. PMID- 1919469 TI - Findings in newborns of cocaine-abusing mothers. AB - Cocaine has recently been shown to affect the outcome of pregnancy when taken by pregnant women. The authors measured fetal concentrations of cocaine and benzoylecgonine and reviewed autopsy and historical data for 62 successive infants who died at less than two days of age and were seen at the Los Angeles County Office of the Chief Medical Examiner-Coroner. Of 43 infants without an obvious cause of death at autopsy, cocaine or benzoylecgonine or both were present in 40%. None of the parameters studied predicted which infants would show cocaine or benzoylecgonine. We conclude that cocaine and benzoylecgonine concentrations should be measured on all infants who die at less than two days of age when the cause of death is not evident at gross autopsy. PMID- 1919470 TI - Postmortem evaluation of serum and urine neopterin concentrations. AB - Cellular immune response is accompanied by the release of neopterin. Increased neopterin levels in urine and serum are observed in patients during viral infections, autoimmune diseases, and allograft rejections and certain malignant diseases. We investigated postmortem neopterin concentrations in urine and serum samples taken from 32 corpses 3 to 69 h (mean 19.3 h) after death. Urine neopterin concentrations in corpses are similar to those of healthy live controls and are independent of the time after death. In contrast, serum neopterin concentrations are frequently greatly increased in corpses, and the levels are higher in sera collected more than 10 h after death in comparison with samples obtained earlier. Neopterin measurement in urine and serum samples of corpses is feasible. It appears likely that urine neopterin concentrations could aid the diagnosis of inflammatory diseases in corpses. PMID- 1919471 TI - Toxicological findings in Federal Aviation Administration general aviation accidents. AB - Blood, urine, and tissue specimens were received from 377 Federal Aviation Administration (FAA) aviation fatalities during fiscal year 1989. Carbon monoxide at less than 10% saturation was found in 94% of the cases, and cyanide at less than 0.5 mg/L was found in 96% of the cases. Ethanol at greater than 10 mg/dL was found in 14.8% of the cases, but only 4.5% were determined to be due to ethanol ingestion from toxicological findings. Excluding nicotine and ethanol, 12.6% of the cases were positive for one or more drugs. Acetaminophen and salicylate were the most frequently found drugs. Cannabinoids were found in 1.3% of the cases and benzoylecgonine in 1.6%. There was minimal use of therapeutic drugs that cause central nervous system depression or stimulation. These results show no consistent pattern of drug involvement in civilian aviation fatalities. PMID- 1919472 TI - Radiographic demonstration of esophageal and tracheal fistulas at autopsy using a contrasting medium that vulcanizes at room temperature. AB - Esophageal and tracheal fistulas, which occur in 0.05% of medicolegal autopsies, were demonstrated in three cases by a postmortem radiographic technique using silicone rubber/lead oxide as a contrasting medium that vulcanizes at room temperature. In one 83-year-old male, a tracheoesophageal fistula was detected, which had developed after surgical repair of an esophageal rupture caused by a flexible fiberoptic endoscope. In a second case, carcinoma of the esophagus in a 78-year-old male had eroded the trachea and arcus of the aorta creating a fatal tracheoesophagoaortic fistula. In a third case, 55-year-old female developed a tracheobrachicephalic artery fistula as a result of an infiltrating cystic adenocarcinoma of the trachea, resulting in a fatal hemorrhage into the trachea. The results of this study indicate that diagnostic radiologic methods using a vulcanized contrasting medium are useful in supplementing normal dissection in autopsy cases with suspected fistulas of the esophagus or trachea. PMID- 1919473 TI - Height estimation from foot and shoeprint length. AB - Foot length displays a biological correlation with height that suggests the latter might be estimated from foot- or shoeprints when such evidence provides an investigator the best or only opportunity to gauge that aspect of a suspect's physical description. Previous utilization of percentages and linear regressions of foot length to make height estimates is reviewed and appraised, as is such use of shoeprints. Newly determined percentages and linear regressions for determining height from foot length for young adult males and females based upon very large U.S. Army anthropometric databases are presented and evaluated. Suggestions are made for the practical employment of shoeprint length, preferably as a direct measurement but also indirectly as a shoe size indicator, for height assessment. PMID- 1919474 TI - Relationship between the piriform aperture and interalar nasal widths in adult males. AB - The piriform aperture of 182 skulls of black and white males in the United States was measured and compared with soft tissue readings taken previously. Statistical analysis indicated that nose width prediction formulas currently utilized in facial reconstruction required modification. Two revised formulas are proposed to improve accuracy of reconstructions: an addition prediction formula for ease of use and a multiplication prediction formula for more precise results on those skulls outside of the mean range. PMID- 1919475 TI - A test of the auricular surface aging technique. AB - A recently developed technique used in the estimation of age at death is based upon the metamorphosis of the auricular surface of the ilium. This technique was designed to be used in seriation to estimate the age distribution of a skeletal sample. However, the technique has also been used in forensic science cases, which must be analyzed on a case-by-case basis. The present study examines the use of the auricular surface technique as the single aging factor. Two hypotheses are tested using a sample of 189 individuals drawn from the Terry Collection, housed at the Smithsonian Institution. The hypotheses are (1) is the method equally applicable across race and sex, and (2) how well does the method perform as the single aging factor? The results indicate that the amount of degenerative change in the auricular surface is not dependent upon race or sex in any given age category. However, the rate of degenerative change is too variable to be used as a single criterion for the estimation of age; the range of estimation error is simply too large for forensic science purposes. PMID- 1919476 TI - Misidentified political figures: an underappreciated danger. AB - A series of twelve patients is presented in which each patient suffered from one or more misidentification syndromes and also misidentified one or more political figures. The fact that misidentification syndromes have been associated with physical violence and that the majority of the patients studied had a history of physical violence suggests that these individuals could pose a significant danger of physical harm to others, including political figures. Persons who threaten political figures should be evaluated for misidentification syndromes. PMID- 1919477 TI - Benzoylecgonine (cocaine metabolite) detection in hair samples of jail detainees using radioimmunoassay (RIA) and gas chromatography/mass spectrometry (GC/MS). AB - Benzoylecgonine (BE) was detected in hair samples using nonproprietary extraction methodology and modifications of well-established radioimmunoassay (RIA) screening/quantitative gas chromatography/mass spectrometry (GC/MS) confirmation procedures. Samples collected anonymously from a population of 48 jail detainees weighed between 5.3 and 61.2 mg. All of the 22 hair samples which had RIA results indicating the presence of BE or immunologically similar substances above a cutoff amount of 1.25 ng/sample (50 ng/mL) were confirmed by GC/MS. Several varieties of hair color and texture were tested, although in each general category there were samples which contained BE as well as other samples which did not reveal detectable amounts of BE. The range of concentrations in 22 hair extracts that screened positive were 0.26 to 18 ng/mg hair as determined by GC/MS. In comparison with other reports of cocaine-related substances in hair, these data show consistent concentrations. PMID- 1919478 TI - Fixed human tissues: a resource for the identification of individuals. AB - Polymorphic genetic loci of the deoxyribonucleic acid (DNA) present in formalin fixed, paraffin-embedded tissues were successfully analyzed by utilizing the polymerase chain reaction. Using this analysis, with three different polymorphic loci [human leucocyte antigen (HLA) DQ alpha, low-density lipoprotein receptor, and parathyroid hormone], fixed tissues representing 14 different individuals were genotyped and could be distinguished from each other. The techniques were further applied to the fixed autopsy tissues of a man in which a question of paternity arose postmortem. Since many individuals have surgical procedures or autopsy, these readily available fixed tissues represent an additional resource for the identification of individuals. PMID- 1919479 TI - Parentage determination on aborted fetal material through deoxyribonucleic acid (DNA) profiling. AB - After a rape, women who are pregnant often elect to abort the fetus. The authors describe ten cases in which deoxyribonucleic acid (DNA) typing was performed on the aborted fetal material to provide evidence of the genetic constitution of the suspect. The problems encountered with this new technique are discussed. PMID- 1919480 TI - Incidental cardiac rhabdomyomas: a significant finding necessitating additional investigation at the time of autopsy. AB - Cardiac rhabdomyomas are rare lesions forming part of the tuberous sclerosis complex that may be responsible for sudden death. As well as remaining clinically occult for variable periods of time, they may, along with other manifestations of tuberous sclerosis, be quite difficult to detect clinically and pathologically. A patient is described in whom multiple cardiac rhabdomyomas were an incidental finding at autopsy following fatal potassium fluoride poisoning. Other gross pathological lesions typical of tuberous sclerosis were present but were quite subtle in appearance. Awareness of the association of cardiac rhabdomyomas with tuberous sclerosis is important so that full examination of organ systems for characteristic lesions can be undertaken during the autopsy, and so that fresh and frozen tissue can be obtained at the time of dissection for further investigation. PMID- 1919481 TI - Association of right coronary artery hypoplasia with sudden death in an eleven year-old child. AB - Congenital coronary artery abnormalities are a rare but well-documented cause of sudden and unexpected death in the pediatric age group. Most reported cases involve both an aberrant origin and course of the abnormal vessel. A case of unexpected death occurring in an otherwise healthy eleven-year-old boy, who had been previously investigated for sudden collapse, is described. The major finding at autopsy was marked disparity in diameter between the coronary arteries due to diffuse hypoplasia of the right coronary artery. This case demonstrates the importance of meticulous examination of the coronary artery system in cases of sudden death in childhood so that significant reduction in luminal cross section will be adequately documented. The possible role played by this finding in the etiology of sudden death is discussed. PMID- 1919482 TI - Death following crude oil aspiration. AB - This is a report on three deaths following oil aspiration by workers in petrol tankers. Lung aspiration was demonstrated by the presence of a yellowish-brown material in the alveolar spaces, which was difficult to identify by optic microscopy. Volatile hydrocarbons from petroleum were identified in lung samples by gas chromatography/mass spectrometry. PMID- 1919483 TI - Cardiac rupture due to severe fatty infiltration in the right ventricular wall. AB - An extremely rare case of sudden death caused by cardiac rupture due to severe fatty infiltration in the right ventricular myocardium is presented. The patient, a 74-year-old woman, had no history of chest trauma, hypertension, or pulmonary disease. The autopsy showed a small tear in the right ventricle and cardiac tamponade, but no coronary artery lesion. In the right ventricular myocardium, muscle fibers were definitely atrophic or absent, with massive fatty replacement. Fatty infiltration of the myocardium, if severe, can be a cause of serious cardiac dysfunction or, occasionally, sudden death. PMID- 1919484 TI - The completeness of the afterbirth: a medical/pathological discussion. AB - Practical problems (with possible medicolegal implications) regarding the interpretation of the completeness of the afterbirth are discussed. The case material was obtained during surgical pathological examination and, later, at the time of autopsy of the same patient. The mother (three weeks following emergency delivery) succumbed to life-threatening complications of an epidural anesthetic accident. PMID- 1919485 TI - Fatal and near-fatal animal bite injuries. AB - Fatal and near-fatal maulings of humans by pit bulls have recently become a topic of major public concern, resulting in the passage of laws in some jurisdictions that make the owner of a pit bull criminally liable for manslaughter if his or her pet causes a human death. The authors recently investigated two cases in which children were fatally injured by pet dogs. In the first case, a 17-day-old girl suffered fatal abdominal injuries when attacked by a pregnant Siberian husky. A 2-year-old girl expired from neck wounds inflicted by a pit bull or a rottweiler or both. Because no expert would testify as to which dog caused the fatal injury, the owner of the animals was not charged under a statute which specified criminality only if a pit bull caused the fatal injury. We also examined a 12-year-old boy who attempted to pet a circus tiger; the animal grabbed his arm with its claws and bit off the arm at the shoulder. The arm could not be reattached, but the child survived. These cases and the differentiation of animal bites from other injuries will be presented. PMID- 1919486 TI - Discussion of "Further evaluation of probabilities in human scalp hair comparison". PMID- 1919487 TI - Distribution of the third digit in breath alcohol analysis. PMID- 1919488 TI - "Sexing" deoxyribonucleic acid (DNA) on DNA fingerprint gel: an internal control for DNA fingerprint evidence. AB - Deoxyribonucleic acid (DNA) isolated from male and female fresh blood samples was processed exactly as for routine DNA fingerprint analysis; that is, the DNA was digested with particular restriction endonucleases and fractionated by agarose gel electrophoresis. Ultraviolet (UV) visualization of ethidium-bromide (EtBr) stained gels revealed a sex-specific banding pattern, which depended only on the restriction enzyme used. By means of this test, which is based on direct detection of particular sex-specific restriction fragments in human DNA digests, the authors succeeded in determining the sex of DNA obtained from biological specimens recovered as criminal evidence in rape cases. The data obtained demonstrate that direct sexing of DNA on DNA fingerprint gel appears to be useful as an intermediate control step in DNA fingerprinting analysis used for the purpose of assailant identification. PMID- 1919489 TI - Lewis blood group determination in bloodstains by planimetric measurement of eluted monoclonal antibodies. AB - Planimetric measurements were employed for reading the results of an elution test to determine Lewis blood groups in dry human bloodstains. In the absorption elution test, two varieties of indicators were used to detect eluted Lewis antibodies. First, 64 blood-stains aged between 2 to 8 months were tested with glutaraldehyde (GLA)-treated erythrocytes (planimetric hemagglutination assay, PMHA). This method demonstrated that dry stains weighing approximately 0.4 mg (equivalent to 3 microliters of whole blood) were sufficient for detection of Lea or Leb antigen. Results were obtained within 1 h. Then, 37 of these stains were tested with Lewis substance-coated latex particles (planimetric latex agglutination assay, PMLA). The presence of Lea and Leb antigen were detected from dry stains weighing 0.1 mg (equivalent to 1 microL of whole blood) within 3 h. Both these assays are faster and simpler with accuracy than the enzyme-linked immunosorbent assay (ELISA). Latex particles coated with Lewis substance are, in particular, strongly agglutinated and show agglutination patterns more clearly than erythrocytes. The blind tests using these two methods properly classified 7 Le(a + b-) and 23 Le(a-b + ) bloodstains; whereas, 5 Le(a-b-) stains were undetermined by the criteria for these tests. These results indicate the usefulness of the PMHA and PMLA for typing Lewis blood groups from small bloodstains. PMID- 1919490 TI - Refining the designs of the future American health care system. PMID- 1919491 TI - Concurrent care. PMID- 1919492 TI - Is it time to consider compulsory national universal service? PMID- 1919493 TI - Economic credentialing and the high cost of Kleenex. PMID- 1919494 TI - Informed consent for blood transfusion. AB - At present, few institutions consider separate informed consent for blood transfusions; rather, the patient gives this consent as part of a more comprehensive statement. This should change in the era of increasing patient's rights. The physician has the moral duty to fully inform the patient of the risks and benefits involved in the planned therapy. A separate consent requires time and paperwork but if done properly, it benefits the patients by increasing their knowledge and autonomy in the transfusion process. PMID- 1919495 TI - Compliance with screening mammography. Survey of primary care physicians. AB - A survey of primary care physicians in the greater Tampa Bay metropolitan area was conducted to determine compliance with screening mammography and associated physician characteristics. Information requested included their age, sex, specialty, and board certification status, and the ages and frequencies that they recommend screening mammography for their patients. A total of 565 physicians responded. Even though 88% indicated they follow American Cancer Society recommendations when advising screening mammography, only 62% were actually in full compliance. A significantly greater percentage of obstetricians/gynecologists were compliant (74%) compared to other specialties (family practice, 57%, p = .006; internal medicine, 56%, p = .007; general practice, 53%, p = .003). Women physicians were more likely to be compliant than men (83% versus 58%, p less than .001), and younger physicians more likely than older physicians (72% versus 49%, p less than .001). There was no significant difference in compliance rates between board certified and noncertified physicians. PMID- 1919497 TI - Oxidants, antioxidants and cardiovascular disease. AB - Basic and clinical studies in the past decade suggest an involvement of oxygen derived free radicals in some cardiovascular diseases including atherosclerosis and hypertension. In atherogenesis evidence indicates that low-density lipoprotein/cholesterol must be oxidized before it can be taken up by the monocytes/macrophages to form foam cells which contribute to the characteristic fatty streak. Free radicals are considered responsible for this oxidation. Population studies reveal that hypertensive patients generally have a lower intake of ascorbic acid and possibly other antioxidants. Ascorbic acid deficiency may lead to defective vasodilation and increased blood pressure due to destruction of certain endothelium-dependent relaxing factors by free radicals. Further studies in this area appear justified. PMID- 1919496 TI - Asthma and diving. AB - Medical opinions conflict as to whether the mild, or infrequent, asthmatic should dive. However, even an asymptomatic asthmatic may have small airway obstruction. PMID- 1919499 TI - Children's programs. PMID- 1919498 TI - Problems with gait in older persons. AB - Gait problems are frequently encountered in elderly patients. Assessment can be made with tests that do not require complex equipment or excessive amounts of time. Most gait disorders result from the interplay of many factors but can respond to medical management, physical therapy, gait training, and correct use of adaptive devices. PMID- 1919500 TI - Advocacy and accuracy. PMID- 1919501 TI - Surface polymers of the nematode-trapping fungus Arthrobotrys oligospora. AB - The nematophagous fungus Arthrobotrys oligospora captures nematodes using adhesive polymers present on special hyphae (traps) which form a three dimensional network. To understand further the adhesion mechanisms, A. oligospora surface polymers were visualized by transmission electron microscopy and characterized by chemical methods. Both traps and hyphae were surrounded by a fibrillar layer of extracellular polymers which stained with ruthenium red. The polymer layer was resistant to most of the chemicals and enzymes tested. However, part of the layer was removed by sonication in a Tris-buffer or by extraction in a chaotropic salt solution (LiCl), and the structure of the polymers was modified by treatment with Pronase E. Chemical analysis showed that the crude extracts of surface polymers removed by sonication or LiCl solution contained neutral sugars, uronic acids and proteins. Gel chromatography of the extracts revealed that the major carbohydrate-containing polymer(s) had a molecular mass of at least 100 kDa, containing neutral sugars (75% by weight, including glucose, mannose and galactose), uronic acids (6%) and proteins (19%). There was more polymer in mycelium containing trap-bearing cells than in vegetative hyphae. SDS-PAGE of the extracted polymers showed that the trap-forming cells contained at least one protein, with a molecular mass of approx. 32 kDa, not present on vegetative hyphae. Examining the capture of nematodes by traps of A. oligospora in which the layer of surface polymers was modified, or removed by chemical or enzymic treatments, showed that both proteins and carbohydrate surface polymers were involved in the adhesion process. PMID- 1919503 TI - Brefeldin A blocks an early stage of protein transport in Candida albicans. AB - Brefeldin A (BFA) inhibited in a dose-dependent manner secretion of the cell surface enzyme acid phosphatase (APase) into the periplasm of Candida albicans and caused intracellular accumulation of enzyme protein. Cells grown in the presence of BFA became more dense, implying that cell-surface growth was also blocked by BFA treatment. The APase that was accumulated intracellularly migrated faster on SDS-PAGE, suggesting less N-linked glycosylation compared with the mature, periplasmic APase produced in the absence of BFA. Pulse-chase experiments and gel-filtration of oligosaccharides released by Endo H treatment suggested that the core-glycosylated precursor form of APase accumulated in the presence of BFA. These results strongly suggested that endoplasmic reticulum (ER)-to-Golgi transport in C. albicans was inhibited by BFA. Aberrant membrane structures were observed in BFA-treated cells. Within 1 h of BFA removal these structures were replaced with rough ER membranes, suggesting that the accumulated membranes were derived from the ER. PMID- 1919502 TI - Chitosomes and chitin synthetase in the asexual life cycle of Mucor rouxii: spores, mycelium and yeast cells. AB - To help understand the subcellular machinery responsible for cell wall formation in a fungus, we determined the abundance and subcellular distribution of chitin synthetase (chitin synthase, EC 2.4.1.16) and chitosomes in the asexual life cycle of Mucor rouxii. Cell-free extracts of ungerminated sporangiospores, hyphae/mycelium in exponential and stationary phase, and yeast cells were fractionated by isopycnic centrifugation in sucrose density gradients. The total amount of chitin synthetase per cell increased exponentially during aerobic germination of spores. In all developmental stages, the profile of chitin synthetase activity encompassed a broad range of sucrose density (d = 1.12-1.22) with two distinct zones: a low-density chitosome zone (d = approx. 1.12-1.16) and a high-density, mixed-membrane zone (d = approx. 1.16-1.22). Chitosomes were a major reservoir of chitin synthetase in all stages of the life cycle, including ungerminated spores. Two kinds of chitin synthetase profiles were recognized and correlated with the growth state. In nongrowing cells (ungerminated sporangiospores and stationary-phase mycelium), the profile was skewed toward lower densities with a sharp chitosome peak at d = 1.12-1.13. In actively growing cultures (aerobic mycelium or anaerobic yeast cells), the entire profile of chitin synthetase was displaced toward higher densities; the average buoyant density of chitosomes was higher (d = 1.14-1.16), and more chitin synthetase was associated with denser (d = 1.16-1.23) membrane fractions. In all life cycle stages, chitosomal chitin synthetase was almost completely zymogenic. In contrast to the enzyme from spores or from growing cells, samples of chitosomal chitin synthetase from stationary-phase mycelium were unstable and contained a high proportion of larger vesicles in addition to the typical microvesicles. The presence of chitosomes in ungerminated spores indicates that these cells are poised to begin synthesizing somatic (= vegetative) cell walls at the onset of germination. The increased buoyant density of chitosomes in actively growing cultures suggests that the composition of these microvesicles changes significantly as they mobilize chitin synthetase to the cell surface. PMID- 1919504 TI - Cell surface structures in osmotically fragile mutants of Saccharomyces cerevisiae. AB - Mutants of Saccharomyces cerevisiae characterized by osmotic fragility showed a marked fibrillar structure on the inner wall surface when studied by two electron microscopic techniques, i.e. freeze-etching of whole native cells and metal shadowing of isolated cell walls. The walls of the mutant cells were more permeable to macromolecules than were those of the wild-type parental strain. The synthesis and assembly of (1----3)-beta-D-glucan wall microfibrils studied in protoplasts of mutant cells were not impaired. It is suggested that the osmotic fragility of the mutant cells is related to the deficiency of the wall structure as a consequence of the srb1 mutation affecting biogenesis of the amorphous (glucan) component. PMID- 1919505 TI - Characterization of Rrh4273I, a restriction-modification system of Rhodococcus rhodochrous ATCC 4273 (Nocardia corallina) which recognizes the same sequence as the Streptomyces albus G SalI restriction-modification system. AB - Rhodococcus rhodochrous ATCC 4275 (Nocardia corallina) has a restriction modification system with the same recognition sequence, methylation site and cleavage site as the SalI restriction-modification system. Both the restriction endonuclease and the DNA-methyltransferase (DNA-MTase) have been partially purified and characterized. The nuclease has requirements of activity similar to SalI, and a native Mr of about 46,000. The DNA-MTase is a protein with an Mr of about 67,000. No DNA homology was detected between the cloned salI restriction modification genes of Streptomyces albus and R. rhodochrous chromosomal DNA. PMID- 1919506 TI - Cloning, sequencing, and expression of the P-protein gene (pheA) of Pseudomonas stutzeri in Escherichia coli: implications for evolutionary relationships in phenylalanine biosynthesis. AB - The pheA gene encoding the bifunctional P-protein (chorismate mutase:prephenate dehydratase) was cloned from Pseudomonas stutzeri and sequenced. This is the first gene of phenylalanine biosynthesis to be cloned and sequenced from Pseudomonas. The pheA gene was expressed in Escherichia coli, allowing complementation of an E. coli pheA auxotroph. The enzymic and physical properties of the P-protein from a recombinant E. coli auxotroph expressing the pheA gene were identical to those of the native enzyme from P. stutzeri. The nucleotide sequence of the P. stutzeri pheA gene was 1095 base pairs in length, predicting a 365-residue protein product with an Mr of 40,844. Codon usage in the P. stutzeri pheA gene was similar to that of Pseudomonas aeruginosa but unusual in that cytosine and guanine were used at nearly equal frequencies in the third codon position. The deduced P-protein product showed sequence homology with peptide sequences of the E. coli P-protein, the N-terminal portion of the E. coli T protein (chorismate mutase:prephenate dehydrogenase), and the monofunctional prephenate dehydratases of Bacillus subtilis and Corynebacterium glutamicum. A narrow range of values (26-35%) for amino acid matches revealed by pairwise alignments of monofunctional and bifunctional proteins possessing activity for prephenate dehydratase suggests that extensive divergence has occurred between even the nearest phylogenetic lineages. PMID- 1919507 TI - Isolation and characterization of a mutant of Neisseria gonorrhoeae that is defective in the uptake of iron from transferrin and haemoglobin and is avirulent in mouse subcutaneous chambers. AB - Iron-uptake mutants of Neisseria gonorrhoeae strain 340 were obtained following treatment with streptonigrin, and one such mutant (Fud14) was characterized. N. gonorrhoeae strain Fud14 was unable to grow with human transferrin or haemoglobin as the sole source of iron, but grew normally with heat-inactivated normal human serum or haemin. Internalization of 55Fe from transferrin by strain Fud14 was only 25% of the parent level. Strain Fud14 (less than or equal to 1 x 10(8) c.f.u.) did not grow in subcutaneous chambers implanted in mice, whereas the parent strain was infective at an ID50 of 4.3 x 10(1) c.f.u. Supplementation of chambers with either normal human serum or haemin resulted in the establishment of strain Fud14 in vivo for at least 240 h post-inoculation. Electroporation of Fud14 with wild-type DNA and selection for growth on medium containing human transferrin resulted in a recombinant (Fud15) that was capable of utilizing haemoglobin, and was virulent in mice. These results suggest that a gonococcal strain defective in the ability to utilize in vivo iron sources is not capable of survival in vivo. PMID- 1919508 TI - Atypical characteristics of the salmonid pathogen Aeromonas salmonicida. AB - Incubation of Aeromonas salmonicida at supra-optimal temperatures, i.e. 30-37 degrees C, resulted in the expression of motility by polar flagella, and changes in sugar fermentation patterns, e.g. loss of acid production from mannitol, loss of the ability to degrade complex molecules (aesculin, DNA, elastin and gelatin), and an increase in antibiotic resistance (notably co-trimoxazole). Motility was enhanced in cultures grown in brain heart infusion broth supplemented with 18% (w/v) Ficoll. PMID- 1919509 TI - Cloning and characterization of the determinant for abortive infection of bacteriophage from lactococcal plasmid pCI829. AB - The genetic determinant for abortive infection of bacteriophage (Abi) from the lactococcal plasmid pCI829 was cloned on a 6.2 kb StuI fragment in Escherichia coli using the shuttle vector pSA3. In Lactococcus lactis subsp. lactis MG1363Sm the resulting recombinant plasmid pCI816 conferred complete insensitivity to the small isometric-headed phage 712 and a reduced plaque size in the case of the prolate-headed phage c2. The determinant was further localized by subcloning and nuclease Bal31 deletion analysis; approximately 2.0 kb of DNA was essential for the expression of the Abi+ phenotype. Nucleotide sequence analysis of this region revealed a putative open reading frame of 1887 base pairs preceded by a putative promotor sequence and ribosome-binding site which exhibited similarity to consensus E. coli and Bacillus subtilis transcription/translation signals. Hybridization experiments indicated that this region was not homologous to the abi determinant from the phenotypically similar lactococcal plasmid pCI750. PMID- 1919510 TI - Mathematical analysis of catabolic function loss in a population of Pseudomonas putida mt-2 during non-limited growth on benzoate. AB - Pseudomonas putida mt-2, harbouring the TOL plasmid PWW0, was grown continuously on benzoate in a phauxostat at a non-limited rate. The gradual decrease in the population carrying the complete TOL plasmid was caused predominantly by a growth rate advantage of spontaneous mutants carrying a partially deleted plasmid (TOL- cells). The growth-rate difference (v) was quantified both by measuring the increase in the dilution rate (from 0.68 to 0.79 h-1; v = 0.11 h-1) and by mathematical analysis of the ingrowth of TOL- cells (v = 0.12 h-1). The latter procedure also established that the segregation rate was of the order of magnitude 10(-5) h-1. Similar values for the growth-rate advantage and the segregation rate were found when both benzoate and succinate were present in non limiting concentrations. It is suggested that the growth-rate disadvantage of the wild-type strain is caused by inhibitory effects of an intermediate in the degradation of benzoate via the plasmid-encoded meta-pathway. PMID- 1919511 TI - Stability of TOL plasmid pWW0 in Pseudomonas putida mt-2 under non-selective conditions in continuous culture. AB - Pseudomonas putida mt-2, harbouring the TOL plasmid pWW0, was grown in chemostat culture under succinate-, sulphate-, ammonium- or phosphate-limitation at different dilution rates. The fraction of mutant cells lacking the plasmid encoded enzymes for the degradation of toluene and xylene (TOL- cells), was determined. Genetic analysis revealed that all TOL- cells isolated harboured partially deleted plasmids, lacking the TOL catabolic genes. The growth-rate advantage of the TOL- cells was quantified from the kinetics of their increase as a fraction of the total population. At a dilution rate of 0.1 h-1 no growth-rate advantage of TOL- cells was found when phosphate or ammonium were limiting. Under sulphate-limitation, ingrowth of TOL- cells was evident but did not follow a straightforward pattern. Under succinate-limitation the growth-rate advantage was the highest, particularly at low dilution rates (about 50% at D = 0.05 h-1). In phauxostat culture, at the maximal growth rate, the growth-rate advantage of TOL- cells was less than 1%. The specific activity in TOL+ cells of the plasmid encoded enzyme catechol 2,3-dioxygenase was relatively high at a low growth rate. PMID- 1919513 TI - An efficient cyanide-degrading Bacillus pumilus strain. AB - A Gram-positive, aerobic, endospore-forming bacterium was isolated by an enrichment technique for the ability to degrade cyanide and was identified as a Bacillus pumilus strain. The bacterium rapidly degraded 100 mg l-1 of free cyanide in the absence of added inorganic and organic substances. The ability to degrade cyanide was linked to the growth phase and was not exhibited before late exponential/early stationary phase. Cyanide-degrading activity could not be induced before this time by the addition of 20 mg cyanide l-1. Production of the cyanide-degrading activity required 0.01 mg Mn2+ l-1 and did not occur at Mn2+ concentrations below 0.002 mg l-1. Cyanide-degrading activity was intracellular and cell-free extracts rapidly degraded cyanide. PMID- 1919512 TI - Bioconversion of 2-hydroxy-6-oxo-6-(4'-chlorophenyl)hexa-2,4-dienoic acid, the meta-cleavage product of 4-chlorobiphenyl. AB - Bacterial conversion of 4-chlorobiphenyl (4-CB) usually proceeds through a pathway involving an initial oxidation of the unsubstituted ring in the 2,3 position followed by a 1,2 meta-cleavage. The meta-cleavage product (MCP) is converted through a single hydrolysis step into chlorobenzoic acid. However, several other acidic metabolites that were not expected as part of this pathway have already been described. In this paper, we used strains of Pseudomonas putida carrying cloned genes from Pseudomonas testosteroni B-356 that are involved in polychlorinated biphenyl (PCB) degradation to demonstrate that several acidic metabolites found in the culture media of various bacteria grown in the presence of 4-CB result from alternative novel bioconversion pathways of MCP. The degradation products of MCP through these pathways were identified as analogues with saturated or shorter side chains or as 4'-chlorophenyl-2-picolinic acid; pathways leading to their formation are proposed. PMID- 1919514 TI - Comparison of growth characteristics of anaerobic fungi isolated from ruminant and non-ruminant herbivores during cultivation in a defined medium. AB - Anaerobic fungi were isolated from rumen fluid of a domestic sheep (Ovis aries; a ruminant) and from faeces of five non-ruminants: African elephant (Loxodonta africana), black rhinoceros (Diceros bicornis), Indian rhinoceros (Rhinoceros unicornis), Indian elephant (Elephas maximus) and mara (Dolichotis patagonum). The anaerobic fungus isolated from the sheep was a Neocallimastix species and the isolates from non-ruminants were all species similar to Piromyces spp. A defined medium is described which supported growth of all the isolates, and was used to examine growth characteristics of the different strains. For each fungus the lipid phosphate content was determined after growth on cellobiose and the resulting values were used to estimate fungal biomass after growth on solid substrates. The ability of isolates from ruminants and non-ruminants to digest both wheat straw and cellulose was comparable. More than 90% and 60%, respectively, of filter paper cellulose and wheat straw were digested by most strains within 60-78 h. Growth of two fungi, isolated from rumen fluid of a sheep (Neocallimastix strain N1) and from faeces of an Indian rhinoceros (Piromyces strain R1), on cellobiose was studied in detail. Fungal growth yields on cellobiose were 64.1 g (mol substrate)-1 for N1 and 34.2 g mol-1 for R1. The major fermentation products of both strains were formate, lactate, acetate, ethanol and hydrogen. PMID- 1919515 TI - Influence of CO2 and low concentrations of O2 on fermentative metabolism of the rumen ciliate Dasytricha ruminantium. AB - The effects of ruminal concentrations of CO2 and O2 on glucose-stimulated and endogenous fermentation of the rumen isotrichid ciliate Dasytricha ruminantium were investigated. Principal metabolic products were lactic, butyric and acetic acids, H2 and CO2. Traces of propionic acid were also detected; formic acid present in the incubation supernatants was found to be a fermentation product of the bacteria closely associated with this rumen ciliate. 13C NMR spectroscopy revealed alanine as a minor product of glucose fermentation by D. ruminantium. Glucose uptake and metabolite formation rates were influenced by the headspace gas composition during the protozoal incubations. The uptake of exogenously supplied D-glucose was most rapid in the presence of O2 concentrations typical of those detected in situ (i.e. 1-3 microM). A typical ruminal gas composition (high CO2, low O2) led to increased butyrate and acetate formation compared to results obtained using O2-free N2. At a partial pressure of 66 kPa CO2 in N2, increased cytosolic flux to butyrate was observed. At low O2 concentrations (1-3 microM dissolved in the protozoal suspension) in the absence of CO2, increased acetate and CO2 formation were observed and D. ruminantium utilized lactate in the absence of extracellular glucose. The presence of both O2 and CO2 in the incubation headspaces resulted in partial inhibition of H2 production by D. ruminantium. Results suggest that at the O2 and CO2 concentrations that prevail in situ, the contribution made by D. ruminantium to the formation of ruminal volatile fatty acids is greater than previously reported, as earlier measurements were made under anaerobic conditions. PMID- 1919516 TI - Thermal inactivation of Listeria monocytogenes studied by differential scanning calorimetry. AB - The effect of NaCl on the thermal inactivation of Listeria monocytogenes has been investigated by conventional microbiological techniques and by using differential scanning calorimetry (DSC). Addition of 1.5 M-NaCl to cells grown at lower NaCl concentrations significantly increases the tolerance of cells to mild heat stress (56-62 degrees C). DSC thermograms show five main peaks which are shifted to higher temperatures in the presence of 1.5 M-NaCl. Measurement of loss of viability in the calorimeter gave good correlation between cell death and the first major thermogram peak at two NaCl concentrations. The time course of the loss of this first peak when cells were heated and held at 60 degrees C in the calorimeter matched the loss of viability, whereas the peak attributable to DNA showed little change during this process. The use of DSC to investigate the mechanisms involved in thermal inactivation is discussed. PMID- 1919517 TI - A study of the candidate virulence factors of Bacteroides fragilis. AB - Bacteroides fragilis strains were classified as virulent or avirulent on the basis of their clearance from the subcutaneous tissues of mice. To determine the factors which may contribute to the virulence of B. fragilis strains, we studied encapsulation, hydrophobicity, growth rate, serum sensitivity, agglutination with erythrocytes of different origin, and neuraminidase production. The strains of the virulent group displayed a higher growth rate in broth and a lower sensitivity to the bactericidal activity of serum than the strains of the avirulent group. They also agglutinated different types of erythrocytes more strongly than did the avirulent strains. No significant differences were found between the two groups of strains as regards encapsulation, hydrophobicity and neuraminidase activity. PMID- 1919518 TI - Multivariate analyses of fatty acid data from whole-cell methanolysates of Prevotella, Bacteroides and Porphyromonas spp. AB - The genus Bacteroides contains a number of biochemically and physiologically heterogeneous groups of organisms and needs taxonomic revision. In this study cellular fatty acids from a number of Bacteroides spp. were identified and quantified using gas chromatography and gas chromatography-mass spectrometry. The chemical data were then subjected to principal components analysis. In B. fragilis, which is the type species of the genus Bacteroides, C3-OH-iso17 was the predominant fatty acid (38.0%) and Cante15 was present in higher amounts (32.7%) than Ciso15 (14.6%). B. fragilis thus differed from all the other species examined: Prevotella (Bacteroides) buccae, P. (B.) oralis, P. (B.) oris, P. (B.) disiens, P. (B.) veroralis, P. (B.) heparinolytica and Porphyromonas (Bacteroides) endodontalis. Principal components analysis also enabled the closely related P. buccae, P. oralis and P. oris to be differentiated. PMID- 1919519 TI - The nucleotide sequence and genome structure of the geminivirus miscanthus streak virus. AB - A tandem dimer of miscanthus streak virus (MiSV) DNA was inserted into the T-DNA of the binary plasmid vector pBIN19 and agroinoculated into several monocotyledonous plants (monocots) using Agrobacterium tumefaciens or A. rhizogenes. Disease symptoms and geminate particles were produced in maize and Panicum milaceum plants, and MiSV-specific double-stranded and single-stranded DNAs were found in these plants. The nucleotide sequence of the infectious MiSV clone, consisting of 2672 nucleotides, was determined. Four open reading frames (ORFs) for proteins of Mr greater than 10K were identified, two (V0 and V2) in the virus (+) sense and two (C1 and C2) in the complementary (-) sense, although C2 did not have an ATG start codon. Unlike other geminiviruses infecting monocots, complementary-sense ORFs did not overlap. Potential splicing donor and acceptor sites were identified in the sequence of the border region between the C terminus of ORF C1 and the N terminus of ORF C2. Amino acid sequences predicted from three (V2, C1 and C2) of these ORFs showed significant homology with the corresponding ORFs of other geminiviruses infecting monocots. A fifth ORF (V1), which showed some homology with ORF V1 of other monocot-infecting geminiviruses despite having a coding capacity for a product of Mr 8.8K, was found just upstream of ORF V2 as observed in those geminiviruses. ORF V0 showed no significant homology with ORFs present in any other geminiviruses. A mutation of V0 indicated that the C-terminal 30% of this ORF was not necessary for infection in maize, but that sequences around the mutated LspI site might have some regulatory role. PMID- 1919520 TI - Nucleotide sequence and gene organization of the 3'-terminal region of chrysanthemum virus B genomic RNA. AB - DNA clones complementary to the 3'-terminal 3426 nucleotides of the genomic RNA of the carlavirus chrysanthemum virus B (CVB) have been sequenced. The sequence contains six open reading frames (ORFs) which encode putative proteins (in the 5' ---3' direction) of Mr 25,749 (ORF2), Mr 11,435 (ORF3), Mr 6984 (ORF4), the triple gene block proteins, a protein Mr 34,638 (ORF5); the coat protein, and a protein of Mr 12,609 (ORF6). The latter protein is basic and contains a putative zinc finger motif. The 5'-proximal ORF1 encodes a product with substantial homology to the C-terminal portions of the putative RNA replicases of two other carlaviruses, potato viruses M and S. The analysis of the minus-sense sequence shows one ORF which encodes a polypeptide of Mr 16,817. The sequenced portion of the CVB genomic RNA contains three short internal non-coding regions, two of which are typical for carlaviruses (those between ORFs 1 and 2, and between ORFs 4 and 5), and one (between ORFs 5 and 6) is unusual. There is significant similarity in the amino acid sequences of the CVB RNA-encoded proteins and the corresponding proteins of other carlaviruses. PMID- 1919521 TI - The sequence between nucleotides 161 and 512 of cowpea mosaic virus M RNA is able to support internal initiation of translation in vitro. AB - Cowpea mosaic virus M RNA is translated in vitro as well as in vivo into two C coterminal polyproteins of Mr 105K and 95K. Initiation of translation of the 95K protein gene occurs at an AUG codon at position 512 of M RNA, 351 nucleotides downstream of the initiation codon of the 105K protein gene at position 161. By employing an in vitro transcription and translation system it was determined that this 351 nucleotide sequence has the capacity to direct ribosomes to initiate translation at a downstream start codon. This effect is independent of the position of this sequence in an mRNA. Furthermore, evidence has been obtained that scanning ribosomes can bypass the AUG at position 161. Thus, both leaky scanning and internal entry are mechanisms for the initiation of translation of the 95K protein gene. PMID- 1919523 TI - Generation of envelope and defective interfering RNA mutants of tomato spotted wilt virus by mechanical passage. AB - During a series of mechanical transfers of tomato spotted wilt virus, two distinct types of mutants were generated. Firstly, a morphologically defective isolate was obtained which had lost the ability to produce the membrane glycoproteins and, as a consequence, was not able to form enveloped particles. Analysis of the genomic RNAs of this isolate suggested that this defect was caused by either point mutations or very small deletions in the medium genomic RNA segment. Secondly, isolates were obtained which had accumulated truncated forms of the large (L) RNA segment. These shortened L RNA molecules most likely represented defective interfering RNAs, since they replicated more rapidly than full-length L RNA and their appearance was often associated with symptom attenuation. Defective L RNAs of different sizes were generated after repeated transfers, and hybridization analysis using L RNA-specific cDNA probes showed that the internal regions deleted varied in length. The presence of defective L RNAs in nucleocapsid fractions as well as in enveloped virus particles indicates that all defective molecules retained the sequences required for replication, encapsidation by nucleocapsid proteins and packaging of the nucleocapsid into virus particles. PMID- 1919522 TI - Non-replicating deletion mutants of brome mosaic virus RNA-2 interfere with viral replication. AB - Naturally occurring defective interfering RNAs (DI-RNAs) and satellite RNAs greatly reduce the accumulation of their helper virus in vivo, but often modulate symptom expression in an unpredictable manner. Deletion mutants Nc/S, Na/M and Sa/Nc + M/S, derived from brome mosaic virus (BMV) RNA-2, failed to replicate when co-inoculated with BMV RNAs-1 and -2 to barley protoplasts. However, the inoculum RNA corresponding to these deletion mutants was extremely stable and could have been mistaken for plus-strand progeny had minus-strand progeny analysis been omitted. These results accentuate the need for such tests in evaluating the ability of mutant viral sequences to replicate. One of the mutants, Nc/S, effectively interfered with the accumulation of BMV RNAs-1 and -2 in barley protoplasts. This non-replicating interfering RNA was termed NRI RNA-2 Nc/S. When present with RNAs-1 and -2 at low inoculum amounts (1 microgram), NRI RNA-2 Nc/S reduced replication of RNA-2, the parental RNA, by 63% and preferentially interfered with minus-strand RNA accumulation. At higher levels (4 micrograms), it completely displaced replication of both RNAs-1 and -2. Mutations eliminating translation of a truncated p2a protein from NRI RNA-2 Nc/S did not alleviate the interference effect, demonstrating that a defective replicase protein was not responsible for the decreased accumulation of genomic RNA. At an NRI RNA: genomic RNA inoculum molar ratio of 1:1, NRI RNA-2 Nc/S reduced the accumulation of all helper virus RNAs by 55%. Since this reduction was seen for both wild-type RNA-3 and delta SGP RNA-3, a deletion mutant of RNA-3 that lacks the subgenomic promoter necessary for coat protein expression, it was evident that the effective interference mediated by NRI RNA-2 Nc/S was not mitigated by encapsidation. The ability of the NRI RNAs to mimic satellite DI RNAs in depressing helper virus replication suggests that their expression in transgenic plants may provide a new and widely applicable approach for inducing resistance to viral infection. PMID- 1919524 TI - A reovirus in the brown planthopper, Nilaparvata lugens. AB - A new virus, belonging to the reovirus group, was found in an apparently healthy colony of the brown planthopper, Nilaparvata lugens, and was referred to as the Nilaparvata lugens reovirus (NLRV). The virus was found in the cytoplasm of the insect cells, sometimes associated with tubular structures, which is one of the characteristic features in tissues infected with reoviruses. The virus was purified by carbon tetrachloride clarification, polyethylene glycol precipitation, differential and CsCl equilibrium centrifugations. The virus has double-shelled particles approximately 65 nm in diameter, containing 10 genome segments of dsRNA. The electrophoretic profile of the dsRNA segments differed from those of viruses associated with rice planthoppers and leafhoppers. Seven proteins were detected in a purified preparation of the virus: four were associated with the core particle and three with the outer shell. A virus antigen was detected in individual insects by ELISA. The virus is retained after injection and is vertically transmitted to the offspring. PMID- 1919525 TI - A single amino acid change in the E2 glycoprotein of Venezuelan equine encephalitis virus affects replication and dissemination in Aedes aegypti mosquitoes. AB - Four monoclonal antibody-resistant variants (MARVs) of Venezuelan equine encephalitis (VEE) virus were used to study mosquito-virus interactions. In vitro experiments using an Aedes albopictus cell line, C6/36, demonstrated that an amino acid change in the glycoprotein E2h epitope (MARV 1A3B-7) decreased virus growth when compared with the wild-type, Trinidad donkey virus, and its vaccine derivative, TC-83. The MARVs replicated as efficiently as the parent virus when inoculated into Aedes aegypti mosquitoes, but MARV 1A3B-7 was restricted in its ability to infect and disseminate from the midgut following oral infection. These results demonstrate that a single amino acid change in the E2 glycoprotein can affect the ability of VEE virus to replicate and disseminate in Ae. aegypti mosquitoes. PMID- 1919526 TI - Fine mapping of canine parvovirus B cell epitopes. AB - In this report we describe the topological mapping of neutralizing domains of canine parvovirus (CPV). We obtained 11 CPV-specific monoclonal antibodies (MAbs), six of which are neutralizing. The reactivities were as determined by ELISA and Western blot (immunoblot) analysis. VP2, the most abundant protein of the CPV capsid, seemed to contain all the neutralization sites. Also, an almost full-length genomic clone of CPV was constructed in the bacterial plasmid pUC18 to enable expression of CPV proteins. All the neutralizing MAbs recognized recombinant VP2 when it was expressed as a free protein in Escherichia coli but not when expressed as a fusion protein with glutathione-S-transferase. When two large fragments containing about 85% and 67% of the C terminus of VP2 were expressed, no neutralization sites were detected. When fusion proteins containing the N terminus were expressed, two linear determinants were mapped, one between residues 1 to 10 of VP2, and the other between amino acids 11 and 23. The peptide 11 GQPAVRNERATGS 23, recognized by MAb 3C9, was synthesized chemically and checked for immunogenicity, not being able to induce neutralizing activity. Although the antibody response in rabbits to all the fusion proteins was uniformly high, the anti-CPV response was very variable. Protein from pCPVEx11, which contains a T cell epitope (peptide PKIFINLAKKKKAG) present in the VP1 specific region as well as the B cell epitopes, seemed to be the most effective in inducing virus neutralization. PMID- 1919527 TI - Defective synthesis of envelope proteins by temperature-sensitive mutants representing complementation groups B and D of respiratory syncytial virus. AB - The phenotypes of two complementing temperature-sensitive (ts) mutants of respiratory syncytial (RS) virus indicate that the mutational lesions involve the attachment (G) and matrix (M) proteins of the viral envelope. Synthesis of the G protein was affected in cells infected with mutant tsA2 (complementation group B); the p50 precursor of the G protein was synthesized normally, but further maturation to the fully glycosylated form was defective at 39 degrees C. A non-ts alteration in the efficiency of cleavage of the F0 precursor to the F1 and F2 subunits of the fusion protein was also observed in tsA2-infected cells, which is consistent with the aberrant non-syncytial plaque morphology induced by tsA2 in certain cells. In cells infected with mutant tsN1 (complementation group D) the M protein disappeared from the soluble cytoplasmic fraction soon after synthesis at 39 degrees C and had a slightly decreased electrophoretic mobility. The M protein of non-ts revertants was stable at 39 degrees C, which links the defect in M protein stability with the tsN1 phenotype. However, the aberrant mobility phenotype remained, suggesting pseudoreversion. These results assign two of the eight complementation groups of ts mutants of RS virus. PMID- 1919528 TI - Role of the gag and pol genes of human immunodeficiency virus in the morphogenesis and maturation of retrovirus-like particles expressed by recombinant vaccinia virus: an ultrastructural study. AB - An ultrastructural study was performed on rabbit epithelial RK-13 cells and CD4+ human T lymphocyte lines infected with various recombinant vaccinia viruses (RVVs) expressing genes of human immunodeficiency virus (HIV): the mature p17 or p24 gag domain alone, the entire or truncated gag gene, the reverse transcriptase domain, or the gag-pol genes with a frameshift mutation. Cells infected with RVVs that produced the gag polyprotein with a predicted Mr of more than 48K showed budding and release of HIV-like particles into the extracellular space. These particles were not observed in cells expressing a truncated gag gene (p17 and p24 regions). Mature HIV-like particles were observed extracellularly when the entire gag gene and the protease region of the pol gene were expressed. In contrast, in cells infected with RVVs that contained the gag-pol gene with a frameshift mutation, neither recognizable budding structures nor extracellular HIV-like particles could be detected. These results suggest that the gag gene, particularly its 3' terminus, is necessary for the assembly of HIV particles. In addition, the protease region of the pol gene seems to be required for morphological maturation of HIV particles, but complete proteolytic cleavage of the gag protein may prevent bud formation. PMID- 1919529 TI - Neutralizing activity of anti-peptide antibodies against the principal neutralization domain of human immunodeficiency virus type 1. AB - Monoclonal antibodies (MAbs) raised against a 15-mer peptide representing the centre of the principal neutralization domain of human immunodeficiency virus type 1 (strain BH10) showed wide variations in neutralizing activity against the homologous strain. The nature of this difference in neutralizing activity was studied by measuring antibody concentration, their affinity for peptide and specificity, by reaction with peptides which differed in the extent of sequence overlap, length and the presence of single amino acid replacements. All MAbs bound to approximately the same region in the principal neutralization domain, within the sequence RIQRGPGRAFV. The peptides with which each antibody was able to react differed by only a few amino acids. The neutralizing activity of each MAb preparation was related to its affinity and concentration; the affinity is related in part to the fine structure of the epitope recognized. MAbs with high affinity for the peptide tended to react only with peptides in which amino acid replacements did not affect the beta-turn potential of the peptide, whereas the reactivity of MABs with low affinity was relatively insensitive to amino acid replacements affecting the beta-turn potential. PMID- 1919530 TI - Genes 1 and 2 of pneumonia virus of mice encode proteins which have little homology with the 1C and 1B proteins of human respiratory syncytial virus. AB - Genes 1 and 2 of pneumonia virus of mice (PVM) consist of 410 and 571 nucleotides and encode proteins of 113 and 156 amino acids respectively. The proteins show no extensive (gene 1 analogous to 1C) or low (gene 2 analogous to 1B) homology to their presumed counterparts in human respiratory syncytial virus (HRSV). The strongest homology is between regions of approximately 35 amino acids located near the carboxy termini of the gene 2 product and the 1B protein with 29% identity, although a lower level of homology can be detected throughout much of these proteins (18% identity overall). These observations contrast with the conservation of 1C and 1B proteins between subgroups of HRSV and with the conservation of nucleocapsid proteins between HRSV and PVM. PMID- 1919531 TI - Transcriptional analyses of baculovirus polyhedrin and foreign gene expression relative to baculovirus p10 mRNA levels. AB - Comparisons have been made between the p10 and polyhedrin mRNA levels recovered from Spodoptera frugiperda cells infected with Autographa californica nuclear polyhedrosis virus (AcNPV). In molar terms and from 18 h post-infection (p.i.), the polyhedrin mRNA species increased to levels one and a half times to twice as high as the p10 levels. The influence of the polyhedrin leader sequence on the expression of a foreign gene under the control of the polyhedrin promoter was investigated using a series of four recombinant baculoviruses expressing the lymphocytic choriomeningitis virus nucleocapsid (N) protein gene. The different recombinants varied in the length and composition of the upstream polyhedrin mRNA leader sequence. The recombinant containing the full-length polyhedrin leader sequence gave levels of N mRNA comparable to those of AcNPV polyhedrin mRNA. These levels were either equal to (12 h p.i.) or higher (18 to 42 h p.i.) than the p10 levels at corresponding times. Three other recombinants, with different lengths of leader sequence, accumulated significantly lower quantities of N mRNA in comparison to the p10 mRNA levels. However the mRNA levels for the three recombinants were similar (20 to 50% of the p10 level) and did not correspond to their N protein expression levels. By comparing the mRNA and protein levels, it is concluded that the sequence between -8 to +1 of the AcNPV polyhedrin translation-initiating ATG has an important function for mRNA transcription (or accumulation), while the sequences between -32 to -8 affect the overall translation efficiencies. PMID- 1919532 TI - Characterization of the VPg-dsRNA linkage of infectious pancreatic necrosis virus. AB - By the use of strong denaturing agents, a genome-linked protein (VPg)-RNA complex was purified from infectious pancreatic necrosis virus. Ribonuclease treatment of 125I-labelled VPg-RNA released a 90K polypeptide identical to the minor structural polypeptide VP1 (the putative RNA polymerase), as determined by peptide mapping. The polypeptide is linked to the RNA by a serine-5' GMP phosphodiester bond. The results identify birnaviruses as the only dsRNA viruses with a VPg, the size of which is the largest of the VPgs of RNA viruses. PMID- 1919533 TI - Evolution of herpesvirus thymidine kinases from cellular deoxycytidine kinase. AB - The thymidine kinases encoded by herpesviruses of higher vertebrates form a distinct group and are unrelated to the thymidine kinases (TKs) of other organisms. Their evolutionary source has not been identified, but our analysis has revealed a clear relationship with a sequence of human deoxycytidine kinase (dCK) published recently. We report the sequence of the putative TK of channel catfish virus, a herpesvirus of a lower vertebrate, and show that it is also related to dCK. We propose, therefore, that the TKs of herpesviruses of higher and lower vertebrates have evolved, either independently or successively, from a cellular dCK. PMID- 1919535 TI - Comparison of viral nucleic acid intermediates at early and late stages of cauliflower mosaic virus infection suggests a feedback regulatory mechanism. AB - An important phase of the multiplication cycle of the pararetrovirus cauliflower mosaic virus (CaMV) is transcription of the viral minichromosome in the nucleus. Leaves of infected turnip plants at the vein clearing stage were found to contain a relatively low level of minichromosome DNA, and abundant viral transcripts and characteristic reverse transcription products. In contrast, at the much later stage of severe leaf chlorosis, an elevated level of minichromosome DNA but less RNA, especially the 35S RNA reverse transcription template, was observed. Changes in the composition of virus nucleic acid intermediates were also seen in roots and stems early, compared with late, in infection. A possible feedback mechanism controlling the level of viral minichromosome DNA and its importance in regulation of the CaMV multiplication cycle are discussed in the light of these observations. PMID- 1919534 TI - Coat protein gene sequences of two cucumber mosaic virus strains reveal a single amino acid change correlating with chlorosis induction. AB - The coat protein genes of two chlorosis-inducing strains of cucumber mosaic virus (CMV) were compared by nucleotide sequence analysis. The predicted amino acid sequences of the encoded coat proteins were compared with those of two other chlorosis-inducing and four mosaic-inducing CMV strains. Overall, the sequences were highly conserved, with more than 95% amino acid sequence identity between any two strains. However, a proline is present at amino acid 129 of all the mosaic-inducing strains, whereas that position is occupied by either a serine or a leucine in the coat proteins of all the chlorosis-inducing strains. The correlation of chlorosis induction and a substitution for proline with leucine or serine at amino acid 129 suggests that this residue is the determinant of chlorosis induction. PMID- 1919536 TI - Prevalence of hepatitis C in tropical communities: the importance of confirmatory assays. AB - The prevalence of antibody to hepatitis C virus (HCV) was estimated in 3 tropical populations using 2 screening ELISAs to detect antibody to the c100-3 antigen and 2 supplementary assays designed to test the specificity of these tests. Two hundred and eighty-six of 385 (74.2%) sera from Kiribati, 17 of 138 (12.3%) sera from Vanuatu, and 39 of 173 (22.5%) sera from Zaire were reactive in the initial screening assay. The proportion of reactive sera which were also reactive in the second screening ELISA varied between populations (55.1% in Kiribati, 85.1% in Vanuatu, and 39.2% from Zaire). Reactive sera were selected at random for confirmatory testing. Only 3 of 49 (6.12%) of sera from Kiribati and 1 of 14 (4.76%) of sera from Vanuatu positive in the initial ELISA were reactive in the confirmatory assays. The proportion of confirmed positive sera from Zaire was higher 8 of 28 (28.5%). Based on the results of these supplementary assays the estimated prevalence of anti-HCV in these populations is 4.8% in Kiribati, less than 1% in Vanuatu, and 6.4% in Zaire. Reliance on a single screening ELISA to estimate the prevalence of anti-HCV in stored sera from tropical communities may lead to a gross over-estimate of the true prevalence in these populations. PMID- 1919538 TI - Unlinked surveillance of the prevalence of HIV infection in antenatal patients in the West Midlands, England. AB - In the course of an unlinked, anonymous survey of anti-HIV seroprevalence among antenatal patients in the West Midlands, carried out between November 1986 and March 1990, seven out of 202,012 patient samples were anti-HIV seropositive. Although the numbers of women infected by heterosexual contact are still low in this region, it is likely that HIV infection is no longer limited to well defined, male risk groups. It is therefore increasingly important to monitor the course of the epidemic through large-scale unbiased surveys of the heterosexual population in order to plan future preventive and health-care strategies. PMID- 1919537 TI - Prevalence of HPV cervical infection in a family planning clinic determined by polymerase chain reaction and dot blot hybridisation. AB - The overall prevalence of human papillomavirus (HPV) cervical infection in 131 women attending a family planning clinic was 7% (HPV 6/11, 16, 18, 31) by dot blot hybridisation, 53% (HPV 11, 16, 31) by polymerase chain reaction (PCR), and 56% by the two methods combined. HPV 16 and 18 were the commonest types (4% each) by dot blot, HPV 16 (39%) by PCR. Fifteen percent of subjects had mildly abnormal cervical cytology (grades 1A, 2A, or 3). There was no significant correlation between cytological abnormality and HPV positivity, or between cytological or HPV status and other postulated risk factors for cervical neoplasia. It is concluded that PCR is considerably more sensitive than dot blot DNA hybridisation in detecting HPV cervical infection in such a "low risk" setting, where HPV copy number may be low. Firm conclusions cannot be drawn from our results regarding a causal role for HPV or other factors in the development of cervical neoplasia. PMID- 1919539 TI - Enzymatic amplification and sequence analysis of precore/core DNA in HBsAg positive patients. AB - Serum or plasma from 69 HBsAg-positive patients was tested for the presence of precore core gene specific DNA by the polymerase chain reaction (PCR). In both healthy individuals (n = 26) and chronic carriers (n = 25), there was a strong correlation between presence of circulating anti-HBe and the absence of detectable HBV genome in serum. In 18 serum samples where HBsAg was the only detectable marker, i.e., anti-HBc-negative specimens, HBV DNA could be detected in three samples. HBV strains from 21 of the 24 PCR-positive samples were sequenced over the precore/core junction. A stop codon at the end of the precore region, described by other workers, was found in strains from two blood donors, one of whom had detectable HBeAg in serum. Conversely, HBV strains from the three anti-HBc-negative patients where DNA of the HBV precore region could be amplified and who had no detectable serum HBeAg or anti-HBe did not have this stop codon. The study indicates that further investigations are required before lack of HBeAg can be correlated with evidence of mutations in the precore region. PMID- 1919540 TI - A randomised controlled trial of recombinant interferon-gamma in Chinese patients with chronic hepatitis B virus infection. AB - Nineteen Chinese patients with chronic hepatitis B virus (HBV) infection, seropositive for HBV e antigen (HBeAg) and HBV DNA on at least three occasions in 6 months, were randomised to receive either recombinant human interferon-gamma (rIFN gamma) 0.1 mg/m2 intramuscularly thrice weekly for 16 weeks (n = 11) or no anti-viral therapy (controls, n = 8). Five patients in the treatment group and four patients in the control group had persistently elevated serum alanine aminotransferases (ALT) of over two times the upper limit of normal before entering into the trial. rIFN gamma had no or minimal inhibitory effect on serum HBV DNA during treatment and no patient developed e-seroconversion or sustained loss of serum HBV DNA. Hepatitic flare, which occurred in a proportion of patients responding successfully to interferon-alpha (IFN alpha) therapy, was not observed with rIFN gamma treatment. Side-effects included pyrexia and mild headache that showed tachyphylaxis and were well tolerated by all patients. In the control group, one patient with elevated pre-entry serum ALT lost serum HBV DNA and seroconverted to anti-HBe. Another patient with elevated ALT lost serum HBV DNA transiently during therapy. In the dose given, rIFN gamma was safe but had no apparent anti-viral effects in Chinese patients with chronic HBV infection. PMID- 1919542 TI - Pharmacological blocking agents for treating substance abuse. AB - Pharmacological blocking agents are an important treatment approach for the current epidemic of drug abuse. This approach is multidisciplinary, ranging from molecular neuroscience for developing these blocking agents to behavioral therapies for establishing treatment delivery systems. This paper outlines the biological, behavioral, and clinical components of the pharmacological blocking agent approach. Clinical results using two blocking agents, naltrexone for opioid abuse and disulfiram for alcohol abuse, are reviewed as a source of leads in developing potential agents for treating sedative and stimulant abuse. While specific pharmacological antagonists have been developed for benzodiazepines, such agents are not yet available for stimulants. Furthermore, the clinical utility of stimulant antagonists may depend on the development of multisite agents that partially block several neurotransmitter systems rather than target a single-system brain receptor. PMID- 1919541 TI - Chronic delta hepatitis in haemophiliacs. AB - The seroepidemiological profile of HBV and HDV was investigated in 640 male haemophiliacs. Twenty-seven of forty-four HBsAg carriers were anti-HDV-IgG positive, 22 were also anti-HDV-IgM positive. A markedly lower prevalence of HDV infection was found in patients with anti-HBc in the absence of HBsAg and anti HBs (6/41). Repeated detection of anti-HDV-IgM in 5/41 individuals of this group indicates that circulating HBsAg is not an absolute prerequisite for chronic HDV infection. Overall, chronically active HDV infection was detected more frequently in quiescent than in active chronic HBV infections. Anti-HDV-IgM was not detected in the absence of anti-HDV-IgG antibodies. Anti-HDV-IgG may disappear after resolution of HDV infection, as indicated by the low prevalence (1/42) in such individuals with past HBV infection as well as by loss of anti-HDV-IgG observed in two patients. PMID- 1919543 TI - Dementia of depression in Parkinson's disease and stroke. AB - Depression is a frequent finding in patients with neurological disorders. These depressions, however, have similar phenomenology, duration, biological markers, and response to treatment as depressions in patients with no known brain injuries (i.e., functional depression). In the present article, we review evidence that suggests the dementia of depression exists among severely depressed patients with cerebrovascular lesions or Parkinson's disease (PD). We conclude that: a) in patients with either stroke lesions or PD, depression is significantly associated with cognitive deficits; b) this association is only true for patients with major depression (i.e., it is not present in patients with minor depression); and c) patients with poststroke depression and patients with PD and depression have a severity and profile of cognitive deficits similar to those found in patients with primary major depression. PMID- 1919544 TI - The pre- and poststerilization predictors of poststerilization regret in husbands and wives. AB - Husbands and wives from 141 tubal sterilization couples and 162 vasectomy couples were interviewed just prior to sterilization and then again 1 and 2 years later. We conducted linear regression analyses to determine the pre- and poststerilization predictors of poststerilization regret in each of the four gender x method groups (tubal husbands, tubal wives, vasectomy husbands, vasectomy wives). We confirmed a number of hypotheses based on the research literature and our own earlier work. Both individual and couple factors contributed to the development of regret, as did both pre- and poststerilization factors. An important finding was the degree to which regret among the nonsterilized respondents (tubal husbands, vasectomy wives) was affected by pre- and poststerilization interaction with their spouses. PMID- 1919545 TI - Depressed subjects unwittingly overreport poor social adjustment which they reappraise when recovered. AB - Potential biases due to acute depressive symptomatology on raters' assessments of social maladjustment derived from patients' reports were assessed in 25 patients responding to pharmacotherapy during medium-term hospitalization. Patients were questioned on two separate occasions about their social maladjustment covering the exact same period (the 4 months preceding hospitalization): the first was during the acute illness phase, and the second a mean of 20.5 days later, when symptoms remitted. In the second report, composite scores for all fields as a whole showed significantly fewer reports of social impairment than did the first. Significant differences from the first to the second evaluation concerning both subjective distress and observable behavior were found in four and three, respectively, of the five "fields" of social adjustment. Although subjective distress was most modified by remission of acute symptoms, even supposedly objective, observable disturbances were significantly affected. These results indicate that acutely depressed patients overreport social maladjustment, which they then more accurately reappraise when symptoms remit. Patients are completely unaware of both the initial bias and of the reappraisal. PMID- 1919546 TI - Acknowledging alcohol problems. The use of a visual analogue scale to measure denial. AB - Despite the frequent mention of denial in the alcohol treatment literature, there appears to be no consensus about its measurement. At its most basic, an operational definition of the term should contain the notion of the drinker refusing to acknowledge or at least minimizing the role of alcohol in his or her difficulties. Visual analogue scales provide a technique for measuring subjective experiences of this type. Subjects from a community-based voluntary agency and an alcohol treatment unit were asked to indicate the magnitude of their problems with alcohol on this scale. Both groups acknowledged high levels of problems with alcohol. Despite this, there was evidence of systematic bias in that half of the sample underestimated the severity of their drinking in comparison to an interviewer's rating using the same scale. A small group was identified that seemed to fit the stereotype of the alcoholic "denier" mentioned so frequently in the treatment literature. There was no relationship between "denial" and subsequent compliance with treatment. PMID- 1919547 TI - Symptomatic reactions to undercover work. AB - The notion of exceptional psychiatric symptoms in agents engaged in undercover work was investigated in a concurrent cross-sectional study of preoperational, operational, and postoperational undercover agents in a federal law enforcement agency. The incidence of psychiatric disturbance and severity of symptomatology were found to be highest among active undercover agents. Mental disturbances tended to be more pronounced among younger agents with little or no prior undercover experience who were engaged in long-term investigations. The symptomatic profiles of distressed agents were similar in pattern to those of general psychiatric outpatients, and these profiles do not support claims of exceptional disturbances brought on by the unique nature of undercover work. Conventional self-report instruments, however, may not have adequately sampled the unusual reactions described in other accounts of undercover distress. PMID- 1919548 TI - Ethnicity and family involvement in the treatment of schizophrenic patients. AB - In a cross-ethnic study of neuroleptic response, the level of family involvement with the treatment of 26 Asian and 26 Caucasian patients was evaluated. Asian family members were intimately involved, Caucasians much less so. These results quantitatively demonstrated the relatively greater importance of working with family members when treating Asian patients. They also indicate that relatively more effort is needed to increase involvement of Caucasian families in the treatment process. PMID- 1919549 TI - Three cases of pharmacotherapy of obsessive-compulsive disorder in the elderly. PMID- 1919550 TI - A successfully treated Dutch case of latah. PMID- 1919551 TI - Neurocognitive features of chronic schizophrenic inpatients. PMID- 1919552 TI - Postpsychosis posttraumatic stress disorder. PMID- 1919553 TI - The prediction of outcome in schizophrenia. IV: Eleven-year follow-up of the Washington IPSS cohort. AB - Two- and five-year follow-up observations of the International Pilot Study of Schizophrenia's Washington cohort provided data bearing on several controversial issues regarding the course of schizophrenia. Forty schizophrenic patients have now been observed 11 years after their index admission. Social, occupational, hospital utilization, and symptom areas of functioning continue to be only modestly correlated with one another and do not become increasingly uniform over time. Initial prognostic variables continue to be more predictive of long-term outcome than are cross-sectional symptom manifestations. Restricted affect at the initial evaluation had been a predictor of 5-year outcome, but it was not a significant predictor of outcome at 11 years. While serious long-term consequences of illness are observed, the follow-up data suggest that the illness tends to reach a plateau of psychopathology early in the course, with as many patients tending to improve in the long-term as those who tend to show further deterioration. PMID- 1919554 TI - Early and long-term effects of electroconvulsive therapy and depression on memory and other cognitive functions. AB - Twenty-seven medication-free, depressed patients (Research Diagnostic Criteria, endogenous subtype) were administered a comprehensive battery testing memory and other cognitive functions before and after a series of bilateral, brief-pulse electroconvulsive therapy (ECT) administered according to a dosage-titration procedure (8.9 +/- 1.981 treatments). A subset of patients (N = 14) were reexamined at 1 month and 6 months after the conclusion of the treatment. Anterograde (verbal and visuospatial tasks), as well as retrograde (famous and personal events), memory function was significantly impaired at the end of the ECT series. By 1 month follow-up, performance had improved to pre-ECT (depression) levels on both anterograde and retrograde tasks and exceeded these by 6 months. The memory deficits induced by ECT were not a consequence of generalized cognitive impairment. Furthermore, depression and ECT were shown to independently affect memory, and recovery from depression was not a consequence of the amnestic action of the treatment. The results generally confirm previous reports regarding the nature of ECT-induced memory impairment, in a different language and culture. They suggest that long-term effects of the treatment on memory are even less prominent than previously observed. PMID- 1919555 TI - Prognostic significance of cerebral status: dimensions of clinical outcome. AB - This report examines the relationship between a set of neurobehavioral predictor variables (premorbid cognitive-perceptual abilities, sensorimotor functions, and complex integrative skills) and three dimensions of clinical outcome (social outcome, work functioning, and rehospitalization) 2 years after discharge from inpatient treatment for a group of psychiatric disorders. Results indicated the strongest relationship was between premorbid ability levels and work performance, particularly maintaining stability of employment or work role function. This finding is discussed from the standpoint of neurological processes underlying early acquisition of basic cognitive-perceptual skills in the prediction of outcome. PMID- 1919556 TI - Risk factors associated with persistence of neuropsychological deficits in persons with organic solvent exposure. AB - This study examined neuropsychological prognosis following organic solvent exposure. Twenty-seven persons with evidence of "mild toxic encephalopathy" were evaluated on two separate occasions with a standard neuropsychological test battery and the Minnesota Multiphasic Personality Inventory. Ratings by experienced clinicians revealed that 50% of exposed persons had improved neuropsychological performance at the second evaluation. The other 50% were rated as having no change or a decline in neuropsychological tests scores. While the majority of persons in the good-outcome group were working at the time of the follow-up evaluation, none of the persons in the poor-outcome group was actively employed. Persons rated as having shown no improvement were significantly more likely to have had a peak exposure--an episode in which they were briefly exposed to a larger than normal amount of solvent. In addition, persons in the poor outcome group reported higher levels of psychological distress, both initially and at the follow-up evaluation. Results from this study suggest that the presence of certain risk factors, namely a peak exposure and psychological distress, may be particularly detrimental for long-term neuropsychological outcome in persons with a history of organic solvent exposure. PMID- 1919557 TI - A Rorschach investigation of attachment and anxiety in antisocial personality disorder. AB - We investigated the constructs of anxiety and attachment in a group of 42 offenders who met the DSM-III-R criteria for antisocial personality disorder. Each antisocial subject's level of psychopathy was assessed with the Hare Psychopathy Checklist (PCL). Three Rorschach variables related to attachment, anxiety, and coping were compared between subjects scoring greater than or equal to 30 (N = 21) on the PCL and subjects scoring less than 30 (N = 21). Comparison Rorschach variables are also presented from a sample of 60 antisocial personality disordered offenders. Moderate psychopaths (PCL score, less than 30) produced texture and diffuse shading responses at a significantly greater frequency than severe, or primary, psychopaths (PCL score, greater than or equal to 30). There was no significant difference in the two groups' propensity for producing vista responses. Although there were no significant differences between the coping index scores, the trend suggests less conflictual functioning in the severe psychopaths. A virtual absence of texture responses in the severe psychopaths, and a significantly greater frequency of diffuse shading responses in the moderate psychopaths, add construct validity to the lack of attachment in psychopaths and the role of anxiety in differentiating secondary from primary psychopathy. We view the presence of vista responses in this population as a measure of a failed grandiose self-structure, and note that it often occurs in the records of moderate psychopaths who also present achromatic color responses. PMID- 1919558 TI - Comparison of successful, unsuccessful, and relapsed Vietnam veterans treated for posttraumatic stress disorder. AB - The present study investigated the differences between veterans who benefited from intensive treatment for posttraumatic stress disorder (PTSD) and those who either relapsed or showed no improvement following treatment. Data from 45 combat veterans with PTSD completing at least 6 weeks of treatment in a partial hospitalization program were utilized. Veterans who had improved following treatment and had maintained a positive adjustment 18 months following treatment were found to have had lower rates of alcohol consumption and greater program participation than those who were unimproved or relapsed. These veterans also obtained lower scores on the MMPI-PTSD subscale, the global indices of the SCL-90 R, and seven of nine individual symptom scales of the SCL-90-R. These results were consistent with other recent reports concerning the existence and characteristics of Vietnam veteran symptom overreporters in studies using the MMPI, and suggest possible treatment outcome predictors for these groups. PMID- 1919559 TI - Skin conductance levels in panic disorder and depression. AB - Skin conductance level (SCL) was measured in 63 subjects with panic disorder, 21 of whom had major depression. Some evidence was found for low SCL being associated with depression, as has been recorded in depression without panic. The standard deviation of SCL was high and it is suggested that the etiology of depression in panic is different from primary depression, at least for some patients. High SCL was not associated with severity of illness. Recordings made in the usual small, isolated, sound-attenuated environment were compared with those made in a larger room with an investigator present for 10 patients and 10 normal controls. Lower SCLs were found in the larger room. PMID- 1919560 TI - The delusion of possession in chronically psychotic patients. AB - Sixty-one chronically psychotic outpatients were grouped according to the presence or absence of a history of delusional possession. Compared with patients without a history of delusional possession (N = 36), possessed patients (N = 25) had significantly more self-reported childhood sexual abuse, higher dissociation scores, more cannabis abuse, more experiences of thought control, and more voices heard inside their heads. These findings support the hypothesis that in some psychotic patients, possession beliefs may reflect childhood trauma and dissociation. PMID- 1919562 TI - Psychological and physiological benefits of passive and aerobic exercise in sedentary middle-aged women. PMID- 1919561 TI - Recurrent nightmares in posttraumatic stress disorder: association with sleep paralysis, hypnopompic hallucinations, and REM sleep. PMID- 1919563 TI - Suicide, homicide, and demographic shifts: an epidemiologic study of regional and national trends. PMID- 1919564 TI - Seasonal differences in the physiology and morphology of crayfish motor terminals. AB - The physiology and morphology of identified crayfish motor terminals were compared at different seasons. We examined initial excitatory postsynaptic potential (EPSP) amplitudes, synaptic fatigue, and the frequency of synaptic varicosities along the motor terminals of an identified phasic motoneuron in animals collected over a period of 5 years. The physiology and morphology of identified crayfish motor terminals are different for animals collected in summer and winter. In winter animals, phasic axon motor terminals in the claw closer muscle produce large EPSPs initially, but show dramatic synaptic fatigue during repetitive stimulation. In summer animals, these terminals produce smaller initial EPSPs, but are more fatigue resistant. Due to their greater fatigue resistance, synaptic terminals have a greater over-all capacity for transmitter release in summer animals than do those of winter animals. Morphologically, terminals in summer animals have more synaptic varicosities, this result supports earlier studies that have shown that fatigue-resistant motor terminals have more synaptic varicosities. Experiments in which the electrical activity of the motoneuron was experimentally altered suggest that these differences in motor terminals may be due to seasonal differences in activity. PMID- 1919565 TI - Release of pedal peptide from Aplysia neurons in primary culture. AB - Pedal peptide (Pep) is a modulatory neuropeptide that is predominantly synthesized in a group of neurons on the dorsal surfaces of the pedal ganglia of Aplysia. Following the determination that Pep is the major peptide selectively present in these neurons in situ, primary cell culture of single Pep-neurons was used to study the release of this neuropeptide. Individual Pep-neurons were grown in culture where they extended many branched neurites with large varicosities. Immunocytology revealed that these newly grown varicosities were intensely Pep immunoreactive. Cultured Pep-neurons, grown in a medium containing radiolabeled methionine, synthesized labeled Pep and transported it into their regenerated neurites. Finally, these neurons released radiolabeled Pep in a calcium- and stimulation-dependent fashion. These results, taken together with previous findings, strongly support the proposition that Pep is a transmitter in Aplysia. PMID- 1919566 TI - Lack of correspondence between mRNA expression for a putative cell death molecule (SGP-2) and neuronal cell death in the central nervous system. AB - Neuronal death during nervous system development, a widely observed phenomenon, occurs through unknown mechanisms. Recent evidence suggests an active, destructive process requiring new gene expression. Sulfated glycoprotein-2 (SGP 2), a secretory product of testicular Sertoli cells has been shown to up-regulate in several nonneural tissues undergoing programmed cell death and in several types of neuronal degeneration. In order to determine if this message up regulates in neurons undergoing developmentally determined cell death, we have studied the expression of SGP-2 mRNA in the developing and adult rat central nervous system (CNS) with in situ hybridization. We also report on the expression of this message in nonneural tissues from several regions of the developing embryo. The developing and adult rat central nervous system as well as widely varied tissues in the rat embryo express SGP-2 mRNA in a pattern that does not correlate with regions undergoing developmental cell death. In the nervous system, SGP-2 mRNA is expressed in neuronal populations including motor neurons, cortical neurons, and hypothalamic neurons at ages when the period of developmental cell death has passed. In a nonneural tissue (palatal shelve epithelium) for which a developmental cell death period has been described, SGP-2 mRNA was not present in the region where cell death occurs. We conclude that SGP 2 mRNA expression cannot be correlated with programmed cell death in neural or nonneural tissues. The results of this study as well as recently reported SGP-2 homologies indicate a possible role for this protein in secretion and lipid transport. PMID- 1919567 TI - Morphology of pioneer and follower growth cones in the developing cerebral cortex. AB - In the developing nervous systems of both invertebrates and vertebrates, neurons must develop precise sets of axonal connections. One strategy used by both orders of animals is to generate a special class of neurons whose axons "pioneer" the first pathways between these cells and their targets. In the developing mammalian telencephalon, the subplate neurons (which are among the first neurons to be generated in development) extend axons to long-distance subcortical targets before the neurons of the deep cortical layers 5 and 6 have been generated. The axons of layer 5 and 6 neurons later follow a similar pathway to form permanent subcortical projections to the thalamus and tectum, and thereafter the vast majority of subplate neurons die. These results have generated the hypothesis that subplate axons may actually be required for the axons of layer 5 and 6 neurons to innervate their appropriate subcortical targets. The complexity of growth cones has previously been correlated with axonal decision making: differences in growth cone morphologies have been noted in comparisons of leading versus following axons (LoPresti, Macagno, and Levinthal, 1973; Nordlander, 1987; Yaginuma, Homma, Kunzi, and Oppenheim, 1991), and at choice points along axon pathways (Raper, Bastiani, and Goodman, 1983; Tosney and Landmesser, 1985; Caudy and Bentley, 1986a,b; Bovolenta and Mason, 1987; Holt, 1989; Bovolenta and Dodd, 1990; Yaginuma et al., 1991). Thus, as a first step toward addressing the question of whether the axons of deep-layer neurons simply follow subplate axons to their targets, we have studied the morphology of cortical growth cones at various points along the corticothalamic pathway and at different stages of development. We examined the brains of fetal ferrets and cats at ages ranging from embryonic days (E) 24 to E50, using the fluorescent lipophilic tracer 1,1 dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI) to reveal the axons and growth cones of cortical neurons. Growth cones were drawn, and quantitative measurements of their complexity were made by counting filopodia and calculating their surface area. No morphological differences were found among growth cones at different points along the corticothalamic pathway at a given age. However, growth cones belonging to early-generated cells (likely to be subplate neurons) are significantly larger and more complex than are the growth cones of later-generated cortical neurons. This evidence is consistent with the suggestion that subplate growth cones actively pioneer the corticothalamic pathway, and that the axons of layer 5 and 6 neurons follow it. PMID- 1919568 TI - Localization of ventral giant interneuron connections to the ventral median branch of thoracic interneurons in the cockroach. AB - A detailed morphological study was performed to localize the probable sites of connections between two identified populations of interneurons (ventral giant interneurons and type-A thoracic interneurons) in the cockroach. Type-A thoracic interneurons (TIAS) appear to play an important role in orienting the cockroach during wind-mediated escape. However, their large number, approximately 100 neurons, precludes analyzing each cell's role electrophysiologically. The TIAS are characterized by a prominent branch located on one or both sides of the ventral median (VM) region of the thoracic ganglion in which their soma resides. The presence of this ventral median branch can be used to predict connectivity with left or right ventral giant interneurons (vGIs) (Ritzmann and Pollack, 1988) and is correlated with the TIA's directional response to wind (Westin, Ritzmann, and Goddard, 1988), suggesting that this is the locus of synaptic connection. Two approaches were employed to address this hypothesis. Morphological overlap of differentially labelled cells (ethidium bromide, Lucifer Yellow) was examined at the light microscopic level to locate areas of possible synaptic contact. Experiments were also performed in which one-half of the vGI input to the TIAs was surgically removed early in postembryonic development. Although no changes in the overall branching pattern were observed, the VM branches on the operated side were significantly shorter than were those on the unoperated side. Thoracic interneurons that do not receive inputs from vGIs were unaffected by this surgery. The data reported here thereby confirm previous observations by localizing the vGI inputs specifically to the VM branch, and provide a morphological cue for predicting connectivity and function. PMID- 1919570 TI - In vitro release of endogenous dopamine from the striatum of the weaver mutant mouse. AB - The weaver mutant mouse has a genetically determined defect in the nigrostriatal dopaminergic system. The present study was undertaken to test the hypothesis that in the weaver mutant mouse, striatal nerve terminals undergo compensatory changes in response to this deficiency. To test this hypothesis, we studied the basal and stimulated release of dopamine from striatal slices of weaver mutant mice and matched controls. By using a superfusion system and concentrating the superfusate by passage over alumina, resting dopamine release could be determined in the weaver mutant despite the fact that striatal tissue content of dopamine in these mice is reduced by greater than 75% compared with control mice. Fractional resting release of dopamine in weaver striatal slices was significantly elevated compared with that in controls, suggesting that the release mechanisms in the weaver may be adapting to overcome the dopamine deficit. Potassium-evoked release (24 and 48 mM potassium) was not significantly different between the two genotypes. In contrast, amphetamine-evoked release (1 microM) was significantly greater in the weaver mice than in controls. In both genotypes, release evoked by amphetamine was completely inhibited by cocaine, implicating the dopamine uptake carrier in this release process. These findings suggest that fundamental differences in dopamine release mechanisms exist between weaver and control mice and support the hypothesis that compensatory mechanisms may develop in neurons in response to dopamine deficits. PMID- 1919569 TI - Angiotensin II increases catecholamine release from bovine adrenal medulla but does not enhance that evoked by K+ depolarization or by carbachol. AB - The effect of angiotensin II on catecholamine release from bovine adrenal medulla has been investigated. In retrogradely perfused, isolated bovine adrenal glands, angiotensin II increased basal efflux of catecholamines, but the presence of angiotensin II did not increase the release of catecholamines evoked either by bolus injections of the secretagogue carbachol or by depolarization with a perfusing solution containing a raised concentration of K+. In chromaffin cells maintained in primary tissue culture, angiotensin II increased 3H release from cells preloaded with [3H]-noradrenaline but did not enhance the release evoked by carbachol or by depolarization with K+. The increase in 3H release evoked by angiotensin II from chromaffin cells in tissue culture was inhibited by its analogue antagonist Sar1,Ala8-angiotensin II (saralasin) and was entirely dependent on the presence of Ca2+ in the experimental medium. These findings suggest that, in the chromaffin cells of the bovine adrenal medulla, angiotensin II acts on specific receptors to cause a calcium-dependent catecholamine release but triggers no additional response that acts synergistically with depolarizing or nicotinic stimuli to augment catecholamine release. PMID- 1919572 TI - Effect of loading doses of L-valine on relative contributions of valine derived from protein degradation and plasma to the precursor pool for protein synthesis in rat brain. AB - "Flooding" amino acid pools with high doses of labeled amino acids of low specific activity has been proposed to minimize the effects of recycling of amino acids derived from protein degradation on the specific activity of the amino acid precursor pool for protein synthesis. We have examined the influence of recycling on the precursor pool for protein synthesis under conditions in which plasma valine concentrations were normal (0.19 mM) and "flooded" (10-28 mM) by comparing the steady-state specific activity of the tRNA-bound valine with that of the plasma valine. Under normal and "flooding" conditions, the relative contributions of valine from protein degradation to the precursor pool were 63 and 26%, respectively; "flooding" with a plasma level of 28 mM raised the brain acid soluble pool level to 3.1 mM but was no more effective in decreasing the relative contribution of valine from protein degradation to the precursor pool than "flooding" with a plasma level of 17 mM valine, which raised the brain acid soluble level only to 2.3 mM. The results of these studies show that "flooding" amino acid pools does indeed reduce the effect of recycling on the precursor amino acid pool for protein synthesis, but it does not totally eliminate it. PMID- 1919571 TI - Metabolism of extracellular adenine nucleotides by cultured rat brain astrocytes. AB - Intact astrocytes cultured from newborn rat cerebral cortex rapidly converted extracellular ATP to ADP. The ATPase responsible was apparently not saturated, even at 750 microM ATP. In contrast, the conversion of ADP to AMP was slow, and the reaction was limiting for the subsequent dephosphorylation process. Adenosine formation was the only fate for AMP. The reaction was catalyzed by 5' nucleotidase with an apparent Km of 55 microM for AMP and appeared to be inhibited by high concentrations of ATP and ADP. Astrocytes were able to take up adenosine with an apparent Km value of 45 microM. Uptake was inhibited by dipyridamole but not by anti-5'-nucleotidase IgG. The results support the proposal that astrocytes play a role in modulating synaptic events involving ATP and adenosine. PMID- 1919573 TI - Neuronal nicotinic acetylcholine receptors in Drosophila: antibodies against an alpha-like and a non-alpha-subunit recognize the same high-affinity alpha bungarotoxin binding complex. AB - ALS and ARD proteins are thought to represent a ligand binding and a structural subunit, respectively, of Drosophila nicotinic acetylcholine receptors (nAChRs). Here, antibodies raised against fusion constructs encompassing specific regions of the ALS and ARD proteins were used to investigate a potential association of these two polypeptides. Both ALS and ARD antisera removed 20-30% of the high affinity binding sites for the nicotinic antagonist 125I-alpha-bungarotoxin (125I alpha-Btx) from detergent extracts of fly head membranes. Combinations of both types of antisera also precipitated the same fraction of alpha-Btx binding sites, a result suggesting that both polypeptides are components of the previously defined class I 125I-alpha-Btx binding sites in the Drosophila CNS. 125I-alpha Btx binding to a MS2 polymerase-ALS fusion protein containing the predicted antagonist binding region showed that the ALS protein indeed constitutes the ligand binding subunit of a nicotinic receptor complex. These data are consistent with neuronal nAChRs in Drosophila containing at least two types of subunits, ligand binding and structural ones. PMID- 1919574 TI - Proteolysis of microtubule-associated protein 2 and tubulin by cathepsin D. AB - The in vitro degradation of microtubule-associated protein 2 (MAP-2) and tubulin by the lysosomal aspartyl endopeptidase cathepsin D was studied. MAP-2 was very sensitive to cathepsin D-induced hydrolysis in a relatively broad, acidic pH range (3.0-5.0). However, at a pH value of 5.5, cathepsin D-mediated hydrolysis of MAP-2 was significantly reduced and at pH 6.0 only a small amount of MAP-2 was degraded at 60 min. Interestingly, the two electrophoretic forms of MAP-2 showed different sensitivities to cathepsin D-induced degradation, with MAP-2b being significantly more resistant to hydrolysis than MAP-2a. To our knowledge, this is the first clear demonstration that MAP-2 is a substrate in vitro for cathepsin D. In contrast to MAP-2, tubulin was relatively resistant to cathepsin D-induced hydrolysis. At pH 3.5 and an enzyme-to-substrate ratio of 1: 20, only 35% of the tubulin was degraded by cathepsin D at 60 min. The cathepsin D-mediated hydrolysis of tubulin was optimal only at pH 4.5. These results demonstrate that MAP-2 and tubulin are unequally susceptible to degradation by cathepsin D. These data also imply a potential for rapid degradation of MAP-2 in vivo by cathepsin D either in lysosomes or perhaps autophagic vacuoles of the neuron. PMID- 1919575 TI - Transferrin and iron uptake by the brain: effects of altered iron status. AB - Transferrin (Tf) and iron uptake by the brain were measured in rats using 59Fe 125I-Tf and 131I-albumin (to correct for the plasma content of 59Fe and 125I-Tf in the organs). The rats were aged from 15 to 63 days and were fed (a) a low-iron diet (iron-deficient) or, as control, the same diet supplemented with iron, or (b) a chow diet with added carbonyl iron (iron overload), the chow diet alone acting as its control. Iron deficiency was associated with a significant decrease and iron overload with a significant increase in brain nonheme iron concentration relative to the controls. In each dietary treatment group, the uptake of Tf and iron by the brain decreased as the rats aged from 15 to 63 days. Both Tf and iron uptake were significantly greater in the iron-deficient rats than in their controls and lower in the iron-loaded rats than in the corresponding controls. Overall, iron deficiency produced about a doubling and iron overload a halving of the uptake values compared with the controls. In contrast to that in the brain, iron uptake by the femurs did not decrease with age and there was relatively little difference between the different dietary groups. 125I-Tf uptake by the brains of the iron-deficient rats increased very rapidly after injection of the labelled proteins, within 15 min reaching a plateau level which was maintained for at least 6 h. The uptake of 59Fe, however, increased rapidly for 1 h and then more slowly, and in terms of percentage of injected dose reached much higher values than did 125I-Tf uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919576 TI - Ultrastructural changes induced by 12-O-tetradecanoylphorbol 13-acetate in pure cholinergic synaptosomes of Torpedo electric organ. AB - We have studied the morphological changes induced by the phorbol ester 12-O tetradecanoylphorbol 13-acetate (TPA) treatment on pure cholinergic synaptosomes from Torpedo electric organ. These changes were studied by both ultrathin sections and freeze-fracture techniques. We found that after a treatment with TPA, a redistribution of synaptic vesicles inside the nerve endings and exocytotic images could be observed. Also, TPA, under conditions that induced the acetylcholine release, did not change the density of intramembrane particles at the synaptosomal protoplasmic hemimembrane leaflet. Similar results were found when calcium was not present in the extrasynaptosomal medium, and our results suggest that acetylcholine release induced by phorbol ester is probably mediated by exocytosis of synaptic vesicles. PMID- 1919577 TI - Iron-melanin interaction and lipid peroxidation: implications for Parkinson's disease. AB - The vulnerability of substantia nigral (SN) melaninized dopamine neurons to neurodegeneration in Parkinson's disease and the selective increases of iron and basal lipid peroxidation in SN indicate that iron-melanin interaction could be crucial to the pathogenesis of this disease. The present study describes, for the first time, the identification and characterization of a high-affinity (KD = 13 nM) and a lower affinity (KD = 200 nM) binding site for iron on dopamine melanin. The binding of iron to melanin is dependent on pH and the concentration of melanin. Iron chelators, U74500A, desferrioxamine, and to less extent 1,10 phenanthroline and chlorpromazine, but not the Parkinson-inducing neurotoxin, 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine, can inhibit the binding of iron to melanin and iron-induced lipid peroxidation. Although melanin alone diminishes basal lipid peroxidation in rat cortical homogenates, it can also potentiate that initiated by iron, a reaction inhibited by desferrioxamine. In the absence of an identifiable exogenous or endogenous neurotoxin in idiopathic Parkinson's disease, iron-melanin interaction in pars compacta of SN may be a strong candidate for the cytotoxic component of oxygen radical-induced neurodegeneration of melaninized dopamine neurons. PMID- 1919578 TI - Adenosine receptors in myelin fractions and subfractions: the effect of the agonist (R)-phenylisopropyladenosine on myelin membrane microviscosity. AB - In this article the existence of A1 adenosine receptors and the absence of A2 adenosine receptors in myelin membranes purified from pig brain white matter are demonstrated. The characterization of (R)-[3H]phenylisopropyladenosine ([3H]R PIA) binding to purified myelin fractions was performed. The distribution of high and low-affinity species of the A1 adenosine receptor was different in heavy, medium, and light myelin. The fluidity of myelin subfractions and of pig brain cortical membranes was estimated; the microviscosity of heavy myelin (5.4 poises) and of cortical membranes (5.1 poises) was similar and less than that of medium (7.8 poises) and light (8.2 poises) myelin. It was also demonstrated that the agonist R-PIA modifies the microviscosity of myelin membranes and that the degree of modification depends on the fluidity of the membrane assayed. These results suggest that adenosine receptors may have an important role in the functionality of myelin membranes. PMID- 1919579 TI - Endo-oligopeptidase A, a putative enkephalin-generating enzyme, in the vertebrate retina. AB - Endo-oligopeptidase A, EC 3.4.22.19, converts small enkephalin-containing peptides into the corresponding enkephalins in vitro. We investigated the presence of endooligopeptidase A in the retina and its possible colocalization with enkephalins in retinal neurons. The specific activity of endo oligopeptidase. A found in pigeon retinae (30.3 +/- 7.3 mU/mg, mean +/- standard deviation) was four times higher than in rabbit retinae (7.0 +/- 1.1 mU/mg). The enzyme activity was not modified by EDTA, but it was enhanced by dithiothreitol and inhibited by zinc and 5,5'-dithiobis(2-nitrobenzoic acid). Immunohistochemical experiments with a purified antiserum against rabbit endo oligopeptidase A revealed labeled neurons in both the inner nuclear layer and the ganglion cell layer of pigeon and rabbit retinae. Double-labeling immunofluorescence experiments demonstrated that about 90% of neurons containing endo-oligopeptidase A-like immunoreactivity also contained [Leu5]-enkephalin-like immunoreactivity. These colocalization results may represent an important step toward the demonstration of the possible involvement of endo-oligopeptidase A in enkephalin generation in vivo. PMID- 1919580 TI - Intracellular pH and catecholamine secretion from bovine adrenal chromaffin cells. AB - To study the role of intracellular pH (pHi) in catecholamine secretion and the regulation of pHi in bovine chromaffin cells, the pH-sensitive fluorescent indicator [2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein] was used to monitor the on-line changes in pHi. The pHi of chromaffin cells at resting state is approximately 7.2. The pHi was manipulated first by incubation of the cells with NH4+, and then the solution was replaced with a NH4(+)-free solution to induce acidification of the cytoplasm. The pHi returned toward the basal pH value after acidification within 5-10 min in the presence of Na+ or Li+, but the pHi stayed acidic when Na(+)-free buffers were used or in the presence of amiloride and its analogues. These results suggest that the pH recovery process after an acid load is due to the Na+/H+ exchange activity in the plasma membrane of the chromaffin cells. The catecholamine secretion evoked by carbachol and Na+ removal was enhanced after the cytoplasm had been made more acidic. It appears that acidic pH favors the occurrence of exocytosis. PMID- 1919581 TI - Specific brain protein changes correlated with behaviourally effective brain transplants. AB - The objective of this study was to identify cellular proteins that are associated with foetal brain transplants effective in reinstating memory function in adult rats with brain lesions. Quantitative memory deficits can be created in rats by lesioning the cholinergic projection system, using ibotenic acid. Previous work suggested that injection of cell suspensions prepared from presumptive cholinergic cells of foetal basal forebrain into adult brain, after such lesions, are most effective in restoring cognitive function. It was not clear, however, whether it was the cholinergic nature of the transplants that was critical for their success or whether other factors were involved. In this study, the proteins present in transplanted tissues and control brains were analysed by two dimensional polyacrylamide gel electrophoresis to identify markers for the cells that were specifically correlated with restoration of cognitive function. On each gel, the relative optical densities of the same 33 selected proteins were measured on an interactive computerised image analyser. The amount of each protein was compared between treatment groups and correlated with four behavioural measurements. Seven of the proteins analysed had levels of expression that were either related to transplantation or correlated with behavioural performance. The proteins of interest were divided into the following three groups: (1) transplant-related proteins, (2) cholinergic transplant-specific proteins, and (3) behaviour-related proteins. Notable among the proteins of interest was one of the cholinergic transplant-specific proteins that was positively correlated with three of the four behavioural measurements and was also the only protein among those analysed that was significantly correlated with choline acetyltransferase (ChAT) levels. This has been identified, by immunoblotting, as glial fibrillary acidic protein, an astrocytic cell marker. These results suggest, therefore, that at least two cell types, astrocytes and ChAT(+)-staining cells, play an important role in the successful recovery of cognitive function. This study also identified possible protein markers for cognitive performance. The level of expression of two of the proteins analysed was not affected by lesioning or transplantation, but was significantly correlated with behaviour. One of these proteins, whose amounts correlated negatively with behavioural measurements, has been identified as neurone-specific enolase, a brain-specific neuronal cell marker. PMID- 1919582 TI - Lactate utilization by isolated cells from early neonatal rat brain. AB - The utilization of lactate, glucose, 3-hydroxybutyrate, and glutamine has been studied in isolated brain cells from early newborn rats. Isolated brain cells actively utilized these substrates, showing saturation at concentrations near physiological levels during the perinatal period. The rate of lactate utilization was 2.5-fold greater than that observed for glucose, 3-hydroxybutyrate, or glutamine, suggesting that lactate is the main metabolic substrate for the brain immediately after birth. The apparent Km for glucose utilization suggested that this process is limited by the activity of hexokinase. However, lactate, 3 hydroxybutyrate, and glutamine utilization seems to be limited by their transport through the plasma membrane. The presence of fatty acid-free bovine serum albumin (BSA) in the incubation medium significantly increased the rate of lipogenesis from lactate or 3-hydroxybutyrate, although this was balanced by the decrease in their rates of oxidation in the same circumstances. BSA did not affect the rate of glucose utilization. The effect of BSA was due not to the removal of free fatty acid, but possibly to the binding of long-chain acyl-CoA, resulting in the disinhibition of acetyl-CoA carboxylase and citrate carrier. PMID- 1919583 TI - Hippocampal kindling in the rat is associated with time-dependent increases in the concentration of glial fibrillary acidic protein. AB - The effect of hippocampal kindling on the regional brain concentration of total glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes, was studied in partially kindled rats, and in fully kindled rats after a post kindling period of 24 h, 1 week, and 2 months. GFAP concentration was measured in arbitrary units by dot-blots. In the hippocampus, dentate gyrus, basolateral amygdala, pyriform cortex, and entorhinal cortex, limbic structures which are known to be involved in the kindling process, there was an increase in GFAP concentration which was maximal in the fully kindled animals studied after 24 h. In most brain areas, GFAP concentration was still elevated 1 week post-kindling, but had declined to control level 2 months post-kindling. A significant increase in GFAP was also found in septum, ventral pallidum/accumbens nucleus, and primary motor cortex of kindled rats with a post-kindling period of 24 h, whereas in several other brain regions GFAP was unchanged. These results suggest that astrocyte activation, indicative of degenerative changes in nearby neurons, is a transient and regional phenomenon in kindling occurring only during the development of the kindled state. PMID- 1919584 TI - The posttranslational arginylation of proteins in different regions of the rat brain. AB - The posttranslational incorporation of arginine into proteins catalyzed by arginyl-tRNA protein transferase was determined in vitro in different rat brain regions. The incorporation was found in all the regions studied, although with different specific activities (pmol [14C]arginine incorporated/mg protein). Of the regions studied, hippocampus had the highest specific activity followed by striatum, medulla oblongata, cerebellum, and cerebral cortex. Electrophoretic analysis of the [14C]arginyl proteins from the different regions followed by autoradiography and scanner densitometry showed at least 13 polypeptide bands that were labeled with [14C]arginine. The radioactive bands were qualitatively coincident with protein bands revealed by Coomassie Blue. There were peaks that showed different proportions of labeling in comparison with peaks of similar molecular mass from total brain. Most notable because of their high proportions were those of molecular mass 125 kDa in hippocampus, striatum, and cerebral cortex; 112 and 98 kDa in striatum and cerebellum; and 33 kDa in hippocampus and striatum. In lower proportions than in total brain were the peaks of 33 kDa in medulla oblongata and cerebral cortex and of 125 kDa in medulla oblongata. PMID- 1919585 TI - Acute regulation of the epidermal growth factor receptor in response to nerve growth factor. AB - PC12 cells possess specific receptors for both nerve growth factor and epidermal growth factor, and by an unknown mechanism, nerve growth factor is able to attenuate the propagation of a mitogenic response to epidermal growth factor. The differentiation response of PC12 cells to nerve growth factor, therefore, predominates over the proliferative response to epidermal growth factor. We have observed that the addition of nerve growth factor to PC12 cells rapidly produces a decrease in surface 125I-epidermal growth factor binding capacity. Unlike previously described nerve growth factor effects on 125I-epidermal growth factor binding capacity, which required several days of nerve growth factor exposure, the decreases we report occur within minutes of nerve growth factor addition: A 50% decrease in 125I-epidermal growth factor binding capacity is evident at 10 min. This rapid nerve growth factor response is concentration dependent; inhibition of 125I-epidermal growth factor binding is detectable at nerve growth factor levels as low as 0.2 ng/ml and is maximal at approximately 50 ng/ml, consistent with known ranges of biological activity. No demonstrable differences in the rate of epidermal growth factor receptor synthesis or degradation were observed in cells acutely exposed to nerve growth factor. Scatchard analysis revealed that acute nerve growth factor treatment decreased the number of both high- and low-affinity 125I-epidermal growth factor binding sites, while the receptor affinity remained unchanged. We have also investigated the involvement of various potential intracellular mediators of nerve growth factor action and of known intracellular modulatory systems of the epidermal growth factor receptor for their capacity to participate in this nerve growth factor activity. PMID- 1919586 TI - Hypothermia prevents the ischemia-induced translocation and inhibition of protein kinase C in the rat striatum. AB - The effect of hypothermia on the ischemia-induced changes in the subcellular distribution of protein kinase C (PKC) (gamma), -(beta II), and -(alpha) and the activity of PKC was studied in striatal homogenates of rats subjected to 20 min of cerebral ischemia. The effect of postischemic cooling was also studied. During normothermic ischemia, PKC(gamma) and -(beta II) increased 3.9- and 2.9-fold, respectively, in the particulate fraction, signifying a translocation of PKC to cell membranes. The levels of PKC(alpha) did not change significantly. PKC activity decreased during ischemia by 52% and 47% (p less than 0.05) in the particulate and cytosolic fractions, respectively, and remained inhibited for the 1 h recovery period. In hypothermic animals, there was no evidence of translocation, and the inhibition of PKC activity was completely abolished. Hypothermia induced in the recovery phase, however, did not affect PKC distribution or activity. The protective effect of intraischemic hypothermia may in part be due to the prevention of the ischemia-induced translocation and subsequent downregulation of PKC, possibly through a temperature-dependent modification of the cell membranes. PMID- 1919587 TI - Novel pyrroles from the Oregon red alga Gracilariopsis lemaneiformis. AB - Two new pyrrole natural products have been isolated from the temperate-water red alga, Gracilariopsis lemaneiformis, as diacetate derivatives. The structures of these C- and N-alkylated pyrroles were determined by spectroscopic methods (principally high field nmr and ms) to be N-(2-acetoxy)-propyl-2-(2-acetoxy) acetopyrrole and N-(2-acetoxy)-ethyl-2-(2-acetoxy)-acetopyrrole. PMID- 1919588 TI - Sesquiterpenoids from Brachylaena hutchinsii. AB - The MeOH extract from the bark of Brachylaena hutchinsii yielded two ketoaldehyde sesquiterpenes, 8-ketocopaenal [1] and 8-ketoylangenal [2], which are also known as brachylaenalones A and B, respectively. In addition to the above-mentioned aldehydes, the corresponding ketoalcohols 8-ketocopaenol [3] and 8-ketoylangenol [4] were also isolated from the same plant, along with a fifth non-ketonic compound, ylangenol [5]. Although the ketoaldehydes 1 and 2 have already been described in the literature, their structures have not been completely established. We describe the isolation, identification, and antibacterial activity of five sesquiterpenes from Bra. hutchinsii and propose new structures for brachylaenalones A and B based on their spectral data. PMID- 1919589 TI - [Isolation and synthesis of espintanol, a new antiparasitic monoterpene]. AB - The in vitro leishmanicidal and trypanocidal activities of a petroleum ether extract of Oxandra espintana have been investigated. Four aromatic monoterpenes were isolated, of which two are novel: espintanol [3a], responsible for the antiparasite activity, and O-methylespintanol [4]. Espintanol was tested in vitro on 20 strains of Trypanosoma cruzi and 12 strains of Leishmania spp. Its structure was determined by spectroscopic methods and confirmed by its preparation starting from carvacrol. PMID- 1919590 TI - Plant metabolites. New compounds and anti-inflammatory activity of Uncaria tomentosa. AB - Bioassay-directed fractionation of the anti-inflammatory extracts of Uncaria tomentosa, using the carrageenan-induced edema in rat paw, has led to the isolation of a new quinovic acid glycoside 7 as one of the active principles. Furthermore, a new triterpene 8 was isolated as its methyl ester. The structures were elucidated by spectral and chemical studies. PMID- 1919591 TI - Microbial models of mammalian metabolism: fungal metabolism of the diterpene sclareol by Cunninghamella species. AB - Microbial metabolism of the diterpene sclareol was studied. Screening studies have shown a number of microorganisms capable of metabolizing sclareol. Preparative scale fermentation with Cunninghamella species NRRL 5695 has resulted in the production of two fungal metabolites that have been characterized as 3 beta-hydroxysclareol and 18-hydroxy-sclareol with the use of 2D nmr techniques. The yield of the two metabolites was improved by utilizing resting-cell suspensions of Cunninghamella species NRRL 5695. PMID- 1919592 TI - Additional bioactive heptenes from Melodorum fruticosum. AB - Four additional new bioactive heptenes, melodorinol [2], homomelodienone [4], 7 hydroxy-6-hydromelodienone [5], and homoisomelodienone [7] have been isolated from Melodorum fruticosum. These compounds were slightly to significantly cytotoxic to human tumor cell lines. Their structures have been determined by comparison of their 1H-nmr, 13C-nmr, and mass spectral data with those of prototype compounds (acetylmelodorinol [1], melodienone 3, and isomelodienone [6]). PMID- 1919593 TI - Anti-AIDS agents, 3. Inhibitory effects of colchicine derivatives on HIV replication in H9 lymphocyte cells. AB - A series of colchicine and isocolchicine derivatives were evaluated as inhibitors of HIV replication in H9 lymphocytes. Colchicine showed only very slight inhibition in the absence of toxicity, as measured by the therapeutic index (IC50/EC50). None of the derivatives inhibited HIV replication in the absence of toxicity. PMID- 1919595 TI - Simple ways to mimic the perivascular inflammatory infiltrates of allergic encephalomyelitis. PMID- 1919594 TI - Neuroaxonal dystrophy in neuronal storage disorders: evidence for major GABAergic neuron involvement. AB - The formation of focal granular enlargements within axons (axonal spheroids or "torpedoes"; neuroaxonal dystrophy) is a well known phenomenon occurring in a variety of neurological diseases. The relative susceptibility of different types of neurons to this kind of axonal pathology, however, is largely unknown. An immunocytochemical study directed at localizing glutamic acid decarboxylase (GAD), the synthetic enzyme for the inhibitory neurotransmitter, gamma aminobutyric acid (GABA), in various CNS regions in feline models of lysosomal storage disorders has revealed vast numbers of axonal spheroids containing this enzyme. In some storage diseases (GM1 and GM2 gangliosidosis), GAD-immunoreactive spheroids were a common occurrence in many brain regions, whereas in other disorders these structures were more limited in distribution (alpha mannosidosis), or were absent (mucopolysaccharidosis type I). Axonal spheroids unreactive for GAD were encountered in large numbers in subcortical white matter in GM2 gangliosidosis, but were infrequently observed in the other diseases. The incidence and distribution of GAD-immunoreactive spheroids in the various diseases under study were found to correlate closely with the type and degree of neurological deficits exhibited by affected animals. This study indicates that the neuroaxonal dystrophy occurring in some types of storage disorders commonly involves axons of GABAergic neurons and suggests that a resulting defect in neurotransmission in inhibitory circuits may be an important factor underlying brain dysfunction in this family of diseases. PMID- 1919596 TI - Sleep-related periodic leg movements (nocturnal myoclonus) due to spinal cord lesion. AB - Ten patients with involuntary leg movements due to myelopathy were studied clinically and polysomnographically. The clinical manifestation and polysomnographical findings of involuntary leg movements were identical to sleep related periodic leg movement (PLM) (nocturnal myoclonus). Since 2 patients had complete transection of spinal cord due to injury or vascular accident, the spinal cord deprived of supraspinal influences was considered to generate the rhythm of PLM. Suppression of the leg movements during REM sleep was not obvious in the patients with complete transection of spinal cord. In addition, PLM alternated from one side to the other 1-4 times a night with intervals of 1-4 h in all patients. This alternation also seemed to be from the spinal cord. This PLM of spinal cord origin was different from spinal myoclonus in their clinical features although both were generated within the spinal cord. PLM of spinal cord origin showed a triple flexion of the ankle, knee and hip, and this was very similar to a flexor withdrawal reflex which all patients exhibited. Therefore, it was suggested that PLM of spinal cord origin has a common mechanisms with spinal automatism. Although all patients had extensor plantar responses, PLM preceded the paresis in three patients and the severity of paresis was variable. There was no laterality of left and right PLMs even in patients with weakness of the leg on one side. This suggested that PLM of spinal cord origin might be induced by the interruption of the tract which was separate from, but runs near the corticospinal tract. PMID- 1919597 TI - Orthostatic changes of cerebral blood flow velocity in patients with autonomic dysfunction. AB - Simultaneous registrations of intracranial blood flow velocity parameters achieved by transcranial Doppler sonography and basic cardiovascular parameters were carried out during orthostatic changes in normal controls, diabetic patients and patients with pandysautonomia. Normal subjects had a rapid increase in heart rate at a constant blood pressure and a slight decrease in cerebral blood flow velocities associated with a mild increase of the pulsatility index (PI) after being tilted from a horizontal to a vertical position. Diabetics showed a fixed heart rate reflecting the disturbed autonomic innervation but only minor changes of cerebral blood flow velocity, which is similar to normal cerebrovascular autonomic regulation. Patients with pandysautonomia had a fixed heart rate associated with a decrease of systemic blood pressure but a failure of compensatory cerebral autoregulation to maintain normal flow velocity values after standing up. The results suggest that in diabetics cerebrovascular autonomic regulation is intact in contrast to cardiac autonomic function, while in patients with pandysautonomia both functions are disturbed. Criteria for the interpretation of autonomic regulatory mechanisms involved in cerebrovascular flow measurements are discussed. PMID- 1919598 TI - Cardiovascular responses to tilting in healthy and diabetic subjects. AB - Cardiovascular responses to tilting from supine to upright and back to supine were investigated by measuring heart rate (HR) and blood pressure (BP) continuously by non-invasive methods. Subjects were 20 healthy controls, 17 diabetic patients (DN) with normal test results for parasympathetic cardiac function and 21 diabetics (DA) with abnormal results. In control subjects, tilting up and tilting back maneuvers induced opposite changes in HR, systolic (SBP) and diastolic BP (DBP). The most obvious responses appeared during the first 30 sec after either maneuver. The best measurements to detect sympathetic vasoconstrictor abnormalities during tilting up were derived from the recovery curve that followed the immediate fall in SBP, abnormal in 6 DN and 14 DA patients, and from the increase in DBP after the maneuver, abnormal in 7 and 16, respectively. Tilting back induced comparatively larger cardiovascular responses. The SBP remained stable after 10 sec in the controls, but increased above normal limits in 7 DN and 20 DA patients. The DBP fell during the first 10 sec in controls, but not in 4 DN and 17 DA patients. Continuous monitoring of BP during tilting is a more sensitive test of autonomic function than classical BP measurements made at a few selected intervals. The results challenge the view that parasympathetic dysfunction precedes and occurs more frequently than sympathetic dysfunction. PMID- 1919599 TI - Modification in the expression and localization of contractile and cytoskeletal proteins in Schwartz-Jampel syndrome. AB - Muscle biopsies taken from 4 patients with clinical diagnosis of Schwartz-Jampel syndrome were analyzed by enzyme-histochemical immunocytochemical and biochemical techniques. In situ distribution of the different myosin heavy chain (MHC) isoforms together with that of the cytoskeletal proteins vimentin, desmin and titin was determined in type I, type IIA, type IIB and type IIC fibers. The same muscle biopsies were analyzed for their content in myosin light chains (MLC) by two-dimensional gel electrophoresis and native myosin isoforms by pyrophosphate gel electrophoresis. The opportunity to study 4 patients of different ages, all members of the same family, permitted us to reveal several interesting features in this rare and so far poorly understood muscle pathology. (i) We observed a predominance of slow (type I) fibers in the oldest patient. (ii) Two classes of small clusters of atrophic type IIC fibers were observed. The first class corresponded to fibers which coexpressed embryonic, fetal and fast, but not slow, MHC isoforms. The fibers also displayed an abnormal distribution of desmin, vimentin and titin. The second class was composed by fibers coexpressing embryonic, fetal, fast and slow, MHC isoforms. In contrast to that observed for the first class, fibers in the second class displayed a normal pattern of expression of desmin, vimentin and titin. (iii) A familial heterogeneity was observed between the 4 patients. The pathological processes involved in the evolution of this syndrome are discussed. PMID- 1919600 TI - Quantitative analysis of monoclonal immunoglobulins in serum of patients with amyotrophic lateral sclerosis. AB - In a prospective study, we analysed the presence of monoclonal immunoglobulin (moIg) in the serum from 30 patients with amyotrophic lateral sclerosis (ALS) and 30 matched controls using a sensitive Western blot technique. The incidence of serum moIg was 60% in the ALS group and 13.3% in the control group. Most ALS sera contained 2 or 3 monoclonal components. They were IgG (72.7%) and IgM (27.3%). These results corroborate the concept of a probable association between ALS and serum moIg. PMID- 1919601 TI - Mononuclear cell trafficking and plasma protein extravasation into the CNS during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice. AB - Cellular traffic and plasma protein extravasation across the blood-brain and blood-spinal cord barrier (BBB) have been studied during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice, using a simultaneous double radioisotope method. There was a general correlation between the clinical course of disease and BBB breakdown, including a resealing of the barrier during remission, although breakdown appeared slightly to precede clinical presentation. The brain was markedly less affected than the spinal cord and was only minimally involved in the relapse phase of disease. PMID- 1919602 TI - Freeze-fracture organization of chromatin and cytoplasm in neurons and astroglia of rat cerebellar cortex. AB - The cytology of the cell nucleus and cytoplasm of neurons and astroglia of the rat cerebellar cortex has been investigated by freeze-fracture electron microscopy. The main differential characteristics in the cytoplasm of the several cell types of the cerebellar cortex were: (1) the organization of endoplasmic reticulum elements, including special configurations of lamellar bodies and hypolemmal complexes, (2) the polarity, extension and arrangement of Golgi cisterns and associated tubulovesicular elements; (3) the connection pattern among different membrane-bounded cellular compartments; and (4) the architecture of endomembranes (i.e. presence of pits and fenestrations). In the nucleus, the main differential features were the the three-dimensional view of the nuclear envelope, the distribution of nuclear pores and the aggregation pattern of chromatin, visualized as clusters of nuclear particles in cross-fractures. The quantitative analysis of chromatin revealed four peaks of nuclear particle sizes (8, 12, 17 and 21 nm) that may correspond to variable degrees of coiling of the polynucleosomal chain in the chromatin fibre. Significant differences were observed in the proportion, numerical density and size distribution of aggregated nuclear particles in heterochromatin domains among the different cell types of the cerebellar cortex. The percentage of nuclear particles in aggregates varied from 10% in Purkinje cells to 64% in granule cells. Astrocytes and Bergmann glia showed intermediate values (about 40%). The percentage of nuclear particles in aggregates showed a significant (P less than 0.05) negative linear correlation with the nuclear volume, the number of pores per unit nuclear volume and the total number of pores per nucleus. In granule cells and astroglia, heterochromatin domains had a greater percentage of large nuclear particles (greater than 10 nm) than did euchromatin domains, whereas in interneurons, Purkinje and Golgi cells heterochromatin and euchromatin showed a similar proportion of large particles. Nuclear particles in euchromatin exhibited a similar pattern of distribution in all cerebellar cells. PMID- 1919603 TI - Ultrastructural organization of slice cultures from rat visual cortex. AB - We have been studying the fine structural organization of slice cultures prepared from the visual cortex of 6-day-old rats and cultured for 2 weeks using a roller culture technique. Neurons in culture exhibited the characteristic cytological differences between perikarya, axons and dendrites. Neuronal and glial processes formed a dense neuropil with minimal extracellular spaces, and within the neuropil there were numerous synaptic contacts. Both morphological types of cortical synapses, type I (asymmetrical) and type II (symmetrical) could be readily identified in slice cultures. The pattern of synaptic connections in culture was remarkably similar to that observed in normal cerebral cortex; asymmetrical synapses were usually found in contact with dendritic spines, less frequently with dendritic shafts, and never on perikarya, whereas symmetrical synapses were found mostly on perikarya, occasionally on dendritic shafts but never on dendritic spines. Synaptic morphology appeared mature after 2 weeks in vitro and did not show the immature features observed at the time of culture preparation. Taken together with our previous light microscopic studies, these results indicate that cortical slice cultures are organotypically organized and serve as a useful model to study mechanisms of cortical development and plasticity. PMID- 1919604 TI - Elevated extracellular potassium is associated with a reduced extracellular space in rat neural lobe in vitro. AB - Increased neural activity of neurosecretory cells is accompanied by large increases in extracellular K+. The possibility that elevations of this ion might involve fluid redistribution and thus affect the size of the extracellular space and the relationship between pituicytes and axons in the rat neural lobe was explored using rapid freezing and freeze-substitution. Neural lobes were incubated for 15 min before freezing either in a normal medium or one containing a 10 mM increase in KCl (high KCl), a 10 mM increase in KCl balanced by an equimolar reduction in NaCl (high KCl-low NaCl), or only a 10 mM reduction in NaCl (low NaCl). A quantitative assessment of the region of good fixation was made to determine the relative fractions occupied by axons, pituicytes and the extracellular space near the neurohaemal contact zone. In addition, the percentage of basal lamina contacted by pituicytes and axons was calculated, as was the degree of enclosure of axons by pituicytes. In neural lobes incubated in normal medium, the extracellular space accounted for approximately 30% of the cross-sectional area of the neuropil and could be divided into two domains: an extended perivascular space (28-29% of total area); and a narrow (approximately 24 nm; approximately 1% of total) space between closely apposed neurosecretory processes or between these processes and pituicytes. Pituicytes occupied almost 60% of the basal lamina at the neurohaemal contact zone, while axons occupied approximately 20%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919605 TI - Structural abnormalities in freeze-fractured sciatic nerve fibres of diabetic mice. AB - Nodal and paranodal regions of myelinated sciatic nerve fibres from diabetic (db/db) mice were examined in freeze fracture replicas. In some fibres, the axolemma was found to display abnormalities in the paranodal region. These include shallow, undifferentiated junctional indentations, thinning of the indentations with widening of the non-junctional grooves between them, particle clusters within the non-junctional grooves, and patches in which axolemmal E-face particles are distributed randomly rather than in the form of linear strings within grooves. Nodal structure, in contrast, is hardly affected. Nodal E-face and P-face particle densities in db/db axons are not significantly different from those in age-matched controls, although we found a few examples in which the E face density fell slightly below the normal range. Occasional fibres showing evidence of paranodal or segmental demyelination were also seen. The results support paranodal pathology as a potential basis for reduced nerve conduction velocity in diabetic nerves but provide no evidence for significant changes in nodal structure or in nodal Na channel density in sciatic nerve fibres of the db/db mouse. PMID- 1919606 TI - Changes in the microvillus cytoskeleton during rhabdom formation in the retina of the crayfish Procambarus clarkii. AB - Changes in the microvillus cytoskeleton during the formation of the light receptive rhabdom in the crayfish retina were examined at four structurally distinct stages. The cytoskeleton of microvilli in early rhabdoms is composed of a regularly packed bundle of 12-25 actin filaments. The polarity of S1 decorated filaments indicates that the plus end of the actin filaments is located at the microvillus tip. The hexagonal packing of filaments within the bundle, their spacing, and the presence of cross-striations along the bundle in longitudinal sections indicate the filaments are held together by cross-linking proteins. Electron microscopic observations and data from three-dimensional reconstructions of individual microvilli indicate that the filaments arise from a concentration of dense material at the tip of the microvillus and extend into the cytoplasm as a rootlet. Over the four developmental stages examined there is an increase in the number of microvilli forming the rhabdomeres and a 50% decrease in the mean cross-sectional area of individual microvilli. During this same period the number of actin filaments forming the microvillus cytoskeleton also decreases. Following this decline, microvilli of late stage rhabdoms, which are structurally similar to adults, contain only two to four filaments. These changes are discussed in relation to the three phases of growth described for stereocilia and brush border microvilli. PMID- 1919607 TI - Macrophages in human sensory ganglia: an immunohistochemical and ultrastructural study. AB - The paper describes the immunohistochemical and ultrastructural features of normal posterior root ganglia in a group of humans aged 1 day to 80 years and compares the findings with those seen in the ganglia of normal rats of various ages, some of which underwent permanent traumatic lesions of the sciatic nerve. In humans, cells with the immunohistochemical reactions of macrophages are present in small number at birth, most of them having an endoneurial position. Subsequently, their number increases and more of them are seen around neurons, where their processes intermingle with those of satellite cells. Ultrastructural studies confirm that, in addition to interstitial cells, a small number of cells in satellite position have features of mesenchymal cells. In this respect, human sensory ganglia differ from those of rodents and this difference may explain why no nodules of Nageotte can be found either in ageing animals or after a permanent damage to the nerve has produced considerable cell loss. Other features observed in human ganglia, but absent in rats, are multiple layers of satellite cells surrounding each neuron and desmosome-like structures between satellite cell processes. Previous studies describing maturation of the satellite-nerve cell complex in animals are confirmed. In addition, the present investigation shows that, in human ganglia, satellite cells acquire a more elaborate structure than in rodents. It is also suggested that mesenchymal cells may play a role in the trophism of nerve cells and their removal after irreversible damage. PMID- 1919608 TI - Multivariate analysis of cardiovascular reflexes applied to the diagnosis of autonomic neuropathy. AB - A battery of cardiovascular reflex tests is usually performed for the diagnosis of autonomic neuropathy. The tests discriminate well between normal and definitely abnormal autonomic function. However, in some patients the results are borderline and their autonomic status cannot be better defined. We performed multivariate statistical analysis of six cardiovascular autonomic tests with the aim of increasing their diagnostic efficiency. Eighty-five healthy subjects and 95 patients at risk for autonomic neuropathy were studied. Principal component analysis and two pattern recognition methods, the Bayesian technique and the SIMCA method, were applied. It was found that: (1) normal models obtained by Bayesian analysis showed very high specificity and sensitivity; (2) a battery of two tests for parasympathetic function (R-R interval variation test, deep breathing) and two tests for sympathetic function (blood pressure responses to standing and to sustained handgrip) provide an appropriate diagnostic approach, if multivariate analysis is used; (3) multivariate analysis allows a more precisely defined assessment of autonomic nervous system function in so-called borderline patients. PMID- 1919609 TI - The thymus in seronegative myasthenia gravis patients. AB - In 5-10% of all patients with typical generalised myasthenia gravis (MG), serum antibody to the acetylcholine receptor (AChR) is undetectable. To determine whether these represent a distinct subgroup, we have compared the thymuses of 14 seronegatives, 70 seropositives and 12 non-myasthenic controls. By quantitative immunohistology on coded sections, the 7 seronegative samples were clearly distinguishable from the controls by the pronounced lymph node-type T-cell areas in the medulla. While these closely resembled those in the seropositive cases, germinal centres were significantly sparser, and total in vitro IgG production was disproportionately low (per B cell) in the 12 cases tested. Furthermore, specific anti-AChR production was never detected in any of these cultures. The data support the view that the medullary T-cell areas are the most consistent abnormality in the MG thymus (though it may not be primary), and they strongly imply that seronegative and seropositive MG are distinct entities. PMID- 1919610 TI - Magnesium deficiency as a cause of acute intractable seizures. AB - Clinical and experimental investigations have shown that magnesium depletion causes a marked irritability of the nervous system, eventually resulting in epileptic seizures. Although magnesium deficiency as a cause of epilepsy is uncommon, its recognition and correction may prove life-saving. Two case reports are presented which emphasize the importance of recognizing hypomagnesaemia in patients with acute intractable seizures. PMID- 1919612 TI - Neurological and neuropsychiatric spectrum of Wilson's disease: a prospective study of 45 cases. AB - Forty-five patients with Wilson's disease (WD) were prospectively studied: 27 had neurological deficits, 12 hepatic signs, and 6 were asymptomatic. Kayser Fleischer rings occurred in 23 of the neurological patients and in only 4 of the hepatic patients. Neurological features were extremely variable with respect to frequency and severity. Most frequent were dysdiadochokinesis (25 patients), dysarthria (23), bradykinesia (17), and posture tremor (14). Fifteen, mainly long term treated patients, presented with rather discrete neurological abnormalities which predominantly consisted of dysarthria and various forms of tremor. Eight patients had a parkinsonian type of neurological WD associated with signs of an organic mood syndrome. Three patients were predominantly hyperkinetic, presenting with dystonic and choreatic movements. In 1 patient, ataxia was the predominant neurological feature. There was a clear-cut correlation between the severity of neurological impairment and the restriction in functional capacity. Nine patients were not able to engage in salaried employment or were retired. Psychiatric symptoms and behavioural disorders were common, varying from mild personality and psychological disturbances to severe psychiatric illness resembling psychotic disorders and major depressive syndromes. Significant mental deterioration was not found in the patients. Disturbances of mood were observed in 12 patients, all of whom had neurological abnormalities. There was a history of an attempted suicide in 7 patients, and a history of an organic delusional syndrome in 3. PMID- 1919613 TI - The time-course of bilateral changes in the reflex excitability of relaxed triceps surae muscle in human hemiparetic spasticity. AB - Short, rapid dorsiflexion of the normal human ankle induces a single, synchronised reflex EMG response in the initially relaxed triceps surae muscle (TS). In subjects in whom hemiparesis is present as a result of a unilateral ischaemic cerebral lesion, a reflex EMG response can be elicited on either side with timing identical to that of the normal response. The magnitude of the response in hemiparetic subjects, however, differs from the normal on both the side contralateral and that ipsilateral to the causative lesion. Furthermore, the magnitude of this response varies over the time-course of spasticity. Contralaterally to the lesion, a gradual increase in the magnitude of the response to imposed displacement occurs. One year after stroke, the response has reached a level significantly larger than normal. Changes in the magnitude of the contralateral Achilles tendon jerk reflex EMG are apparent earlier than changes in the response to imposed displacement, with exaggerated tendon jerks already being apparent between 1 and 3 months after stroke. On the side ipsilateral to the lesion, a profound depression of the response to imposed displacement is visible as early as a month after stroke. This depression diminishes over the 1st year, but the response has not even then returned to normal values. These changes are not reflected in the ipsilateral tendon jerk response, which remains normal throughout this period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919614 TI - Is progression in postencephalitic Parkinson's disease late and age-related? AB - Follow-up data are presented of ten patients with autopsy-proven postencephalitic Parkinson's syndrome (PEP) (mean age at death: 56.0 years) with regard to motor and psychic deterioration over a period of institutional observation between 3 and 30 years. Four patients showed deterioration of their Hoehn-Yahr score of at least one grade. These patients did not differ statistically with respect to age of occurrence of lethargic encephalitis, interval to PEP, age at start of PEP, duration of survival with PEP, and age at death. Motor deterioration in these patients seems to be attributed more to inherent disease progression, rather than to an age-related process. Clinical and pathological evidence for this conclusion is presented. PMID- 1919611 TI - Acute and chronic neuroborreliosis with and without CNS involvement: a clinical, MRI, and HLA study of 27 cases. AB - Of the 96 serologically confirmed neuroborreliosis cases seen in our clinic between 1983 and 1988, 11 patients had mild to moderate and 4 patients had serious cerebral and/or spinal cord symptoms. Nine of these 15 patients with CNS involvement exhibited a primary chronic course of the illness. After high-dose intravenous therapy with penicillin, doxycycline or cefotaxime, given mostly in combination with cortisone, gradual recovery occurred with normalization of CSF findings characteristic of neuroborreliosis, and normalization of significantly elevated Borrelia burgdorferi IgG antibody titres in CSF and serum. Brain MRI and CT showed evidence of or were suggestive of vascular involvement which correlated with clinical symptoms in 11 of the 15 patients with CNS involvement. Brain MRI changes that were similar but much slighter in number and intensity were seen in 5 of 12 neuroborreliosis patients without clinical signs of CNS involvement (lymphocytic meningoradiculitis; Bannwarth's syndrome). The frequencies of the HLA-DR7 (75%), HLA-B44 (50%) and HLA-A29 (33%) antigens in 12 neuroborreliosis patients with clinical symptoms of CNS involvement were significantly different from the frequencies in 12 neuroborreliosis patients without CNS involvement and in 100 control subjects. Diagnostic criteria of active neuroborreliosis are proposed. PMID- 1919615 TI - The implementation of ab initio quantum chemistry calculations on transporters. AB - The RHF and geometry optimization sections of the ab initio quantum chemistry code, GAMESS, have been optimized for a network of parallel microprocessors, Inmos T800-20 transputers, using both indirect and direct SCF techniques. The results indicate great scope for implementation of such codes on small parallel computer systems, very high efficiencies having been achieved, particularly in the cases of direct SCF and geometry optimization with large basis sets. The work, although performed upon one particular parallel system, the Meiko Computing Surface, is applicable to a wide range of parallel systems with both shared and distributed memory. PMID- 1919616 TI - Molecular dynamics simulation of the renin inhibitor H142 in water. AB - H142 is a synthetic decapeptide designed to inhibit renin, an enzyme acting in the regulation of blood pressure. The inhibiting effect of H142 is caused by a reduction of a -Leu-Val-peptide bond (i. e. C(= O)-NH----CH2-NH). The conformational and dynamical properties of H142 and its unreduced counterpart (H142n) was modelled by means of molecular dynamics simulations. Water was either included explicitly in the simulations or as a dielectric continuum. When water molecules surround the peptides, they remain in a more or less extended conformation through the simulation. If water is replaced by a dielectric continuum, the peptides undergo a conformational change from an extended to a folded state. It is not clear whether this difference is a consequence of a too short simulation time for the water simulations, a force-field artifact promoting extended conformations, or if the extended conformation represents the true conformational state of the peptide. A number of dynamic properties were evaluated as well, such as overall rotation, translational diffusion, side-chain dynamics and hydrogen bonding. PMID- 1919617 TI - Conformational analysis. Part 16. Conformational free energies in substituted piperidines and piperidinium salts. AB - The conformational free energies (-delta G degree) of a number of 4-substituted piperdines and piperidinium salts have been determined by the J-value method. For the 4-substituted piperdines (R = Me, Phenyl, CO2Et, Br, OH, F) the relative conformer energies are almost identical to those of the analogous cyclohexanes. The methyl and phenyl compounds showed no change in the couplings on protonation, implying no change in the conformer energies. In contrast, in the remaining compounds with polar 4-substituents an almost constant stabilisation of the axial conformer of ca. 0.7 -0.8 kcal mol-1 was observed on protonation. In three cases (R = F, OH and Br) the conformational preference is reversed on protonation and the axial form is favored. The conformer energies of both the free bases and the piperidinium salts can be quantitatively predicted by molecular mechanics calculations using the COSMIC force-field, in which the electrostatic interactions are calculated by a simple Coulombic model with the partial atomic charges in the molecules given by the CHARGE2 routine, and an effective dielectric constant of five. The precise agreement obtained demonstrates conclusively that the electrostatic interactions between the substituents and the protonated nitrogen are the cause of the conformational changes on protonation, and that these can be modelled successfully using existing force-fields. PMID- 1919618 TI - A molecular model for the active site of S-adenosyl-L-homocysteine hydrolase. AB - S-adenosyl-L-homocysteine hydrolase (AdoHcy hydrolase, EC 3.3.1.1), a specific target for antiviral drug design, catalyzes the hydrolysis of AdoHcy to adenosine (Ado) and homocysteine (Hcy) as well as the synthesis of AdoHcy from Ado and Hcy. The enzyme isolated from different sources has been shown to contain tightly bound NAD+. Based on the 2.0 A-resolution X-ray crystal structure of dogfish lactate dehydrogenase (LDH), which is functionally homologous to AdoHcy hydrolase, and the primary sequence of rat liver AdoHcy hydrolase, we have derived a molecular model of an extended active site for AdoHcy hydrolase. The computational mutation was performed using the software MUTAR (Yeh et al., University of Kansas, Lawrence), followed by molecular mechanics optimizations using the programs AMBER (Singh et al., University of California, San Francisco) and YETI (Vedani, University of Kansas). Solvation of the model structure was achieved by use of the program SOLVGEN (Jacober, University of Kansas); 56 water molecules were explicitly included in all refinements. Some of these may be involved in the catalytic reaction. We also studied a model of the complex of AdoHcy hydrolase with NAD+, as well as the ternary complexes of the enzyme, NAD+, and substrate or inhibitor molecules. Our refined model is capable of explaining part of the redox reaction catalyzed by AdoHcy hydrolase and has been used to differentiate the relative binding strength of inhibitors. PMID- 1919619 TI - pi-SCF-molecular mechanics PIMM: formulation, parameters, applications. AB - A pi-SCF/Molecular Mechanics method (PIMM) for the calculation of heats of formation, molecular geometries and charge density distributions of organic molecules is described. The method combines a pi-SCF molecular orbital calculation and the sigma-charge evaluation procedure PEOE of Marsilli and Gasteiger with molecular mechanics. The formulas and parameters used are given. A series of results for small molecules is presented and compared with experimental data. PMID- 1919620 TI - The computational design of test compounds with potentially specific biological activity: histamine-H2 agonists derived from 5-HT/H2 antagonists. AB - The previously proposed models for the recognition and activation of 5-HT and histamine-H2 receptors, which were employed to explain the antagonist activity of LSD at both of these receptors, as well as the selective antagonism for H2 receptors by SKF-10856 and 9,10-dihydro-LSD, are used herein to design a compound to test the H2-receptor model. The design strategy attempts to construct a compound with potentially selective H2 agonism. The design scheme maintains features which were previously used to explain selective recognition of SKF-10856 and 9,10-dihydro-LSD as well as reintroduces the chemical features proposed to be responsible for H2 activation. The existence of the H2 recognition and activation features in the proposed compound is verified, in a previously proposed model, by computational studies of the molecular electrostatic potentials and shifts in the tautomeric preference. PMID- 1919621 TI - Burnout in oncology--physician heal thyself. PMID- 1919623 TI - Transfusion-associated graft-versus-host disease. PMID- 1919622 TI - Biochemical modulation: a modality that has come of therapeutic age. PMID- 1919624 TI - Mitoxantrone, fluorouracil, and high-dose leucovorin: an effective, well tolerated regimen for metastatic breast cancer. AB - Between September 1988 and August 1990, we treated 35 women with metastatic breast cancer with a novel regimen containing mitoxantrone, fluorouracil (5-FU), and high-dose leucovorin. This regimen was designed to take full advantage of the favorable toxicity profiles of these agents while maintaining a high level of activity. All patients had received previous chemotherapy (adjuvant only, 15 patients; at least one metastatic regimen, 20 patients). Seven patients had received previous doxorubicin, but none within 6 months of study entry. Of 31 assessable patients, 20 (65%) had objective responses (two complete, 18 partial), with a median response duration of 6 months (range, 3 to 16+ months). Four patients with bone metastases (abnormal bone scan only) and pain were not considered assessable by strict response criteria; two of these patients had sustained symptomatic relief for 6 and 8 months, respectively. Myelosuppression was the most frequent toxicity but was mild in most patients; only four hospitalizations for fever and neutropenia were required (2% of courses). No severe thrombocytopenia occurred and no RBC transfusions were required. Alopecia, mucositis, and nausea/vomiting were uncommon and were not severe in any patient. The combination of mitoxantrone, 5-FU, and high-dose leucovorin is well tolerated and active as a first- or second-line treatment for metastatic breast cancer. Comparison with other standard regimens for breast cancer is indicated. PMID- 1919625 TI - Phase II study of mitoxantrone, leucovorin, and infusional fluorouracil for treatment of metastatic breast cancer. AB - A new combination of mitoxantrone, folinic acid (leucovorin), and infusional fluorouracil (5-FU) was administered to 57 previously treated patients with metastatic breast cancer to evaluate the response rate, response duration, and toxicity of this regimen. Fifty-three patients who received 313 courses of therapy were assessable for response and toxicity. Median age was 48 years (range, 33 to 80 years), and the patients had received an average of 1.5 chemotherapy regimens before this study. Of 53 assessable patients, 24 (45%, or 42% of all entered patients) experienced partial responses (PRs) with a median duration of 6 months (range, 2 to 13 months). Nine (69%) of 13 assessable patients without prior doxorubicin treatment responded, compared with 15 (38%) of 40 with prior doxorubicin (P less than .05). Toxicity was generally mild with dose reductions necessitated more often by mucositis and/or diarrhea than by myelosuppression. One patient with prior high-dose doxorubicin treatment developed congestive heart failure. The combination of mitoxantrone, leucovorin, and infusional 5-FU is an active and well-tolerated regimen for metastatic breast cancer and deserves further evaluation in patients without prior doxorubicin therapy. PMID- 1919626 TI - Adjuvant tamoxifen in early-stage breast cancer: effects on intercurrent morbidity and mortality. AB - Intercurrent mortality and the pattern of inpatient hospital care was studied among 1,846 postmenopausal patients included in the Stockholm randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no adjuvant endocrine therapy. The median follow-up time was 54 months (range, 2 to 123 months). The patients were matched to the Swedish National Registry of Causes of Death and a computerized register covering about 95% of all hospital admissions in Stockholm County. There was no significant difference in the pattern of intercurrent mortality among the tamoxifen and control patients. The total number of hospital admissions was similar in both groups, but the tamoxifen patients were admitted significantly less frequently because of immunologic diseases (relative risk [RR] = 0.4; 95% confidence interval [CI], 0.2 to 0.9). Admissions because of thrombotic diseases were slightly, but not significantly, more frequent among the tamoxifen patients (RR = 1.2; 95% [CI], 0.6 to 2.3). The risk of hospital stay for benign gynecologic diseases other than prolapse or uterine bleeding was increased in the tamoxifen group (RR = 3.2; 95% CI, 1.2 to 8.6). No significant differences were found for diseases related to arteriosclerosis or osteoporosis. The study confirms and extends previous reports, which have shown that tamoxifen has few and usually mild side effects. However, the current results should be judged cautiously because of the relatively short median follow-up time (4.5 years) and the limitation of data in detecting morbidity that does not necessarily result in hospitalization. PMID- 1919627 TI - Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases. AB - We used monoclonal antibodies to identify occult micrometastases in the bone marrow of 49 patients with operable (stage I and II) breast carcinoma. Follow-up (mean, 29 months; median, 30 months) revealed that 12 patients recurred. The presence of bone marrow micrometastases (BMM) was significantly associated with early recurrence (P less than .04). The estimated 2-year recurrence rate for patients with no BMM detected (BMM-) was 3%; in patients with BMM, the 2-year recurrence rate was 33%. When BMM and axillary lymph node (LN) status were combined, groups of patients at low risk (LN-, BMM-; 2-year recurrence rate, 0%) and high risk (LN+, BMM+; 2-year recurrence rate, 42%) for early recurrence were identified. Bone marrow tumor burden was related to early recurrence. Among patients with BMM, those who did not recur had on average fewer extrinsic cells in their marrow than those who recurred (15 v 43 cells, respectively). Multivariate analysis comparing BMM, LN+ versus LN-, and tumor size (less than or equal to 2 cm v greater than 2 cm) revealed no factor independently associated with early recurrence. Peripheral tumor burden of BMM (0 or less than 10 extrinsic cells v greater than or equal to 10 extrinsic cells) was the only independent predictor of early recurrence (P less than .003). In conjunction with conventional prognostic factors, particularly axillary LN status, evaluation for BMM might be used to stratify patients for adjuvant treatment programs. Because this pilot study involved few patients with short-term follow-up, the results should be interpreted with caution. The examination of bone marrow for micrometastases remains an experimental procedure; the clinical usefulness of the test will be established through larger studies with long-term follow-up. PMID- 1919628 TI - Limb-sparing surgery without radiotherapy based on anatomic location of soft tissue sarcoma. AB - From 1980 through 1986, 119 patients with soft tissue sarcomas of the extremities were referred to our tumor center either before surgery (n = 78) or immediately after incisional biopsy or marginal excision (n = 41). The tumors were classified according to anatomic location at admittance as subcutaneous (n = 40), intramuscular (n = 30), and extramuscular tumors (n = 49). Open biopsy was omitted in 75 of the 78 patients referred before surgery; the preoperative diagnosis was based on physical and radiographic findings and fine-needle aspiration cytology. The surgical intention for subcutaneous tumor was to obtain a wide margin, which required a cuff of fat tissue around the tumor and inclusion of the deep fascia beneath the tumor. A wide margin for an intramuscular tumor implied no open biopsy and an unbroken muscle fascia or thick muscle cuff around the tumor (primary myectomy). The 70 patients with subcutaneous and intramuscular tumors were all treated by local surgery. A wide margin was obtained in 56 patients who were not given radiotherapy. During a median follow-up of 5 years (range, 3.5 to 10 years), four of these 56 patients--47 of whom had high-grade malignant tumors--had a local recurrence. We conclude that routine combination of limb-sparing surgery with adjuvant radiotherapy is not necessary in patients with soft tissue sarcoma. Two thirds of soft tissue sarcomas of the extremities are primarily subcutaneous or intramuscular tumors, the majority of which can be treated by local surgery without local adjuvant therapy with a local recurrence rate of less than 10%, irrespective of malignancy grade. PMID- 1919629 TI - Cisplatin, carboplatin, and cyclophosphamide combination chemotherapy in advanced stage ovarian carcinoma: an Eastern Cooperative Oncology Group pilot study. AB - Cyclophosphamide (CTX) 600 mg/m2, carboplatin 280 mg/m2, and cisplatin 50 mg/m2 were administered on day 1 every 4 weeks to 41 previously untreated ovarian cancer patients with residual disease greater than 2.0 cm after primary laparotomy. Of 22 patients with measurable disease treated with up to eight cycles of therapy, the overall clinical response rate was 73% (exact 95% confidence interval [CI], 50% to 89%), with 50% complete response (CR). Six of 11 clinical CR (cCR) patients underwent surgical restaging; three pathologic CRs (pCRs) and three pathologic partial responses (pPRs) with residual disease less than 2.0 cm were documented. Fourteen patients had nonmeasurable but assessable disease; the clinical response rate was 57% (Cl, 29% to 82%) with two (14%) CRs. Second-look surgery was performed in one of the two cCR patients; a pPR was documented. Five patients with nonassessable disease were stable during chemotherapy; two underwent surgery and had pCRs. The median time to treatment failure (TTF) was 14.8 months, and median survival for the 41 patients is 26.7 months. Overall, 37% of the patients had progression-free intervals of at least 2 years, and 27% have survival times in excess of 3 years. Hematologic toxicity was substantial but manageable, with 58% and 66% experiencing a granulocyte nadir less than 500/microL and a platelet nadir less than 50,000/microL, respectively. One treatment-associated fatality occurred as a result of leukopenic sepsis and renal failure in the setting of progressive disease and ureteral obstruction. Mild to moderate nausea and vomiting occurred in most patients, but none experienced severe ototoxicity or peripheral neuropathy. Over all courses, 73% of the projected dose intensity of CTX and carboplatin and 86% of cisplatin were delivered. Since granulocytopenia and thrombocytopenia were dose-limiting, the addition of colony-stimulating factors that support both myeloid and megakaryocyte precursors may permit further dose intensification. PMID- 1919630 TI - Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin. AB - Phase II trials of second-line intraperitoneal (IP) cisplatin-based therapy in patients with ovarian cancer have demonstrated the ability of this approach to produce objective antitumor responses, including surgically defined complete responses (CRs), in individuals with persistent small-volume disease after front line cisplatin-based intravenous (IV) treatment. To examine the influence of a prior response to systemic cisplatin on the activity of second-line IP cisplatin, we retrospectively analyzed two phase II trials of cisplatin-based IP therapy in persistent/recurrent ovarian cancer conducted at our institution. Of the 89 assessable patients on the two trials, 52 (58%) had previously responded to IV cisplatin. The overall response and CR rates to second-line IP cisplatin-based therapy in this previously responding population were 56% and 33%, respectively, compared with overall response and CR rates in the 37 nonresponders to IV cisplatin of 11% and 3%, respectively (P less than .001; chi 2, 1 df). In the 36 patients responding to systemic cisplatin and whose largest tumor mass measured less than 1 cm at IP cisplatin initiation, a 42% CR rate was observed, compared with a 7% CR rate in the 14 patients with the same bulk of disease who had previously failed to respond to systemic cisplatin (P less than .025). We conclude that a prior response to systemic cisplatin strongly influences the antineoplastic activity of second-line IP cisplatin in ovarian cancer. PMID- 1919631 TI - Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study. AB - In a pilot clinical trial, treatment of patients with advanced colorectal carcinoma with the combination of fluorouracil (5FU) and recombinant interferon alfa-2a (IFN) resulted in objective tumor regression in 62% of patients. To confirm these findings in a multiinstitutional setting, a phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) in 1989. The treatment regimen was identical to that used in the earlier study: 5FU 750 mg/m2/d for 5 days as a continuous infusion followed by weekly outpatient bolus therapy and IFN 9MU subcutaneously beginning day 1 and administered three times per week. Doses were modified for gastrointestinal, hematologic, and neurologic toxicity and for fatigue, similarly to those used in the previous pilot trial. Thirty-eight patients were registered; 36 are evaluable for response (one lost to follow-up and one with nonmeasurable disease). All patients had metastatic or locally recurrent disease beyond the scope of resection; 31 of 38 had liver metastases, and 20 of 38 had two or more sites of involvement. Eight patients had grade 4 toxicities, including sepsis (nonneutropenic) (one), watery diarrhea (two), and granulocytopenia (six). Grade 3 neurologic toxicities were observed in two (5%) patients and included slurred speech and gait disturbance. Objective response was 42% (95% confidence interval [Cl], 27% to 58%), including one clinical complete responder and 14 partial responders. Among the responding patients, the median time to treatment failure was 8 months. Two patients remain on treatment at 10+ and 16+ months: median survival has not been reached. The results of this multiinstitutional trial suggest that the addition of IFN to 5FU enhances the objective response rates achieved in patients with advanced colorectal carcinoma and that the toxicities of this regimen are acceptable. PMID- 1919632 TI - A pilot study of interferon alfa-2a in combination with fluorouracil plus high dose leucovorin in metastatic gastrointestinal carcinoma. AB - Thirty-one assessable patients with metastatic adenocarcinoma of the gastrointestinal tract were entered onto a pilot study designed to assess the impact of recombinant interferon alpha-2a (rIFN alpha-2a) on the toxicity and pharmacokinetics of fluorouracil (5-FU) and leucovorin (LV). Patients received an initial cycle of 5-FU (370 or 425 mg/m2/d) with LV (500 mg/m2/d) for 5 days. If tolerated, the patient received the same dose of 5-FU/LV for the second cycle on days 2 to 6, with rIFN alpha-2a at 5 x 10(6) or 10 x 10(6) U/m2/d on days 1 to 7, or with 3 x 10(6) U/m2/d on days 1 to 14. In 26 matched cycles, rIFN alpha-2a administration was associated with an increased incidence of dose-limiting mucositis and diarrhea and a significantly lower median platelet nadir; rIFN alpha-2a did not significantly affect the median WBC or granulocyte nadir. Dose limiting toxicity occurred in all six patients entered at 425 mg/m2/d of 5-FU/LV within two cycles. The majority of patients treated with 370 mg/m2/d of 5-FU/LV and 10 x 10(6) U/m2/d rIFN alpha-2a experienced grade 3 to 4 mucositis and diarrhea, whereas patients receiving 3 x 10(6) and 5 x 10(6) U/m2/d rIFN alpha-2a had acceptable toxicity. Administration of rIFN alpha-2a was associated with a dose-dependent decrease in 5-FU clearance. The increase in the area under the 5 FU concentration-time curve (AUC) was 1.3-fold and 1.5-fold in patients receiving 5 x 10(6) and 10 x 10(6) U/m2/d rIFN alpha-2a, respectively. Thus, the increase in 5-FU toxicity with rIFN alpha-2a may be explained by alterations in 5-FU pharmacokinetics. In 22 patients without prior 5-FU therapy, three complete (13.6%) and seven partial (31.8%) responses were seen, for an overall response rate of 45.4% (95% confidence interval, 24.4% to 67.8%). Since the 5 x 10(6) U/m2/d dose of rIFN alpha-2a increased the 5-FU drug exposure and was associated with acceptable toxicity, we recommend its further evaluation as given on days 1 to 7 in combination with 5-FU 370 mg/m2/d, with high-dose LV given on days 2 to 6. PMID- 1919633 TI - The in vivo immunomodulatory effects of recombinant interferon gamma plus recombinant tumor necrosis factor-alfa. AB - We conducted a phase I study in which an intramuscular injection of interferon gamma (IFN gamma) at 10, 50, or 100 micrograms/m2 was followed 5 minutes later by an intramuscular injection of 10, 50, or 100 micrograms/m2 of tumor necrosis factor-alfa (TNF alpha) at another site every other day for 20 days (10 doses). The addition of TNF alpha to IFN gamma reduced both the magnitude and duration of IFN gamma-mediated effects on peripheral blood monocyte expression of Fc receptors (FcRs) and HLA-DR and production of hydrogen peroxide. This inhibition was related to the dose of TNF alpha. On the other hand, TNF alpha and IFN gamma appeared to have an additive stimulatory effect on the production of neopterin by monocytes. The highest serum levels of neopterin were detected in patients who received the highest doses of both IFN gamma and TNF alpha. Thus, conflicting conclusions regarding the effect of the combination on immune activation are possible. If the activation of peripheral blood monocytes is the appropriate surrogate measure of the immune enhancement of the combination, then the simultaneous administration of IFN gamma and TNF alpha is ineffective, and future attempts to exploit the potential additive or synergistic effects of this combination of cytokines in humans may need to explore sequential administration schemata. On the other hand, if serum neopterin levels are a more reliable index of immune activation, simultaneous administration of 100 micrograms/m2 IFN gamma and 50 micrograms/m2 TNF alpha every other day (the maximally tolerated dose [MTD]) should be used in phase II testing. This dilemma points out the limitations of currently available methods of human immune assessment and the inadequacies in our capacity to gauge what particular immune measure or set of measures predict for in vivo antitumor effects. PMID- 1919634 TI - Successful treatment of acute myeloid leukemia beyond first remission with autologous bone marrow transplantation using busulfan/cyclophosphamide and unpurged marrow: the British autograft group experience. AB - The results in 34 adult patients with acute myeloid leukemia (AML) who have undergone autologous bone marrow transplantation (ABMT) using busulfan and cyclophosphamide (Bu/Cy) in 12 United Kingdom (UK) centers have been analyzed. There were 19 females and 15 males; median age was 40 years (range, 21 to 62 years). Nine patients were in first relapse; 25 were in second remission. The median time of first remission for the whole group was 11.5 months (range, 1 to 56 months). All the patients in first relapse and six patients in second remission received first remission marrow. The leukemia-free survival (LFS) for the patients in first relapse was 33%, with a median follow-up of 20 months. The LFS for the patients in second remission was 48% with a median follow-up of 26 months. The length of second remission exceeds the length of first remission in 14 patients. Considerable toxicity with hemorrhagic cystitis (four patients; none fatal), venoocclusive disease (four patients; one fatal), pneumonitis (four patients; one fatal), intracranial hemorrhage (two patients; two fatal) has occurred. There have been four procedure-related deaths (12%). Hematologic recovery was satisfactory for neutrophils (median time to 0.5 x 10(9)/L, 22 days [range, 11 to 101 days]), but very slow for platelets (median time to 50 x 10(9)/L, 62 days [range, 15 to 1,080 days]). This study suggests that the use of Bu/Cy with ABMT for patients beyond first remission in AML compares favorably with chemotherapy, and although the procedure-related mortality is acceptable, it is associated with protracted platelet recovery. PMID- 1919635 TI - Allogeneic bone marrow transplantation for relapsed and refractory lymphoma using genotypically HLA-identical and alternative donors. AB - Twenty-two patients, ages 16.6 to 43.9 years (median age, 30 years), with relapsed or refractory lymphoma were treated by allogeneic bone marrow transplantation after high-dose chemotherapy with or without total body irradiation (TBI). Seven patients had Hodgkin's disease, four had low-grade histology non-Hodgkin's lymphoma (NHL), seven had intermediate-grade NHL, and four had high-grade NHL. Of the 22 patients, 17 received T-cell (CD-3)-depleted marrow after intensive pretransplant chemoradiotherapy, and five received T-cell replete grafts after chemotherapy-based preparative regimens. Five patients were transplanted from donors other than genotypically HLA-identical siblings: four from partially HLA-matched relatives, and one from a phenotypically HLA-identical unrelated donor. Acute graft-versus-host disease (GVHD) was less than or equal to grade II in all patients, and chronic GVHD was limited or absent in all but one patient. Of the 21 assessable patients, 17 (80.9%) achieved complete remissions. Death due to transplant-associated complications occurred in five patients, and five patients have relapsed. Thirteen patients are alive, and 12 are continuously relapse-free at a median follow-up of longer than 28 months (range, greater than 10 to greater than 58 months) from transplant. The cumulative probability of treatment failure from relapse or progression of lymphoma was 29% (95% confidence interval [CI], 12% to 51%), while the actuarial lymphoma-free (ie, event-free) survival plateau is 54.6% (95% CI, 34% to 76%). For young patients with advanced malignant lymphoma, allogeneic bone marrow transplantation appears superior to salvage chemotherapy for achievement of long-term, lymphoma-free survival and may be preferable to autologous bone marrow transplantation for selected patients. PMID- 1919636 TI - Phase I-II study of two consecutive courses of high-dose epipodophyllotoxin, ifosfamide, and carboplatin with autologous bone marrow transplantation for treatment of adult patients with solid tumors. AB - We describe a phase I-II study of two consecutive 5-day courses of a three-drug regimen of ifosfamide (IFM), carboplatin (CBDCA), and either etoposide (VP-16) (regimen 1) or teniposide (VM-26) (regimen 2) in high doses together with autologous bone marrow transplantation (ABMT), for previously treated patients with ovarian carcinoma (OC), germ cell tumors (GCT), gestational trophoblastic disease (GTD), or oat cell carcinoma (OCC). Forty-four patients entered the study. Two patients with OC received regimen 1, and 22 were given regimen 2. Sixteen patients with GCT, two with GTD, and two with OCC were treated with regimen 1. Six patients (13%) died of toxicity. Nephropathy and esophagitis were the dose-limiting toxic effects. The maximum-tolerated doses (MTDs) were 1,500 and 200 mg/m2/d for 5 days for IFM and CBDCA, respectively, in combination with VP-16 250 mg/m2/d for 5 days (regimen 1), and 150, 1,500, and 200 mg/m2/d for 5 days for VM-26, IFM, and CBDCA, respectively (regimen 2). The response rate of patients with OC was 78% (complete response [CR], 14%). For patients previously resistant to chemotherapy, the response rate was 70%. There were no long-term disease-free survivors among patients with OC. The response rate of patients with GCT was 60% (CR, 33%). All responders with GCT were resistant to previous chemotherapy. Unmaintained CRs lasted 2, 6, 8+, 27+, and 37+ months. Of the two patients with GTD, one with previous resistance to chemotherapy attained a CR of 18+ months. One patient with OCC attained a CR lasting 6 months. The regimen possesses great antitumor activity. It produced CRs of long duration in a number of patients with GCT and GTD who were previously resistant to chemotherapy. PMID- 1919637 TI - Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease. AB - Fifty-six consecutive patients with advanced Hodgkin's disease considered incurable with further conventional chemotherapy were entered into a protocol that included high-dose cyclophosphamide (7.2 g/m2), carmustine (BCNU; 0.6 g/m2), and etoposide (VP16-213; 2.4 g/m2) (CBV) followed by autologous bone marrow transplantation (BMT). Prior combination chemotherapy had failed in all the patients, and all but five had been previously treated with both mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, and vinblastine with or without dacarbazine (ABV[D]). Thirty-four eligible patients received short-course conventional chemotherapy and/or involved-field radiotherapy before CBV. However, formal restaging was not performed after these conventional therapies; ie, the therapies were not used to select responding patients for transplantation, and all who received such therapy subsequently received CBV and autologous marrow grafts. Forty-four patients (80%; 95% confidence interval [CI], 69% to 91%) achieved a complete response after CBV and BMT. Performance status at protocol entry and the use of conventional cytoreduction therapy before CBV correlated with response. Median follow-up is now 3.5 years (range, 2.5 to 5.0 years). Kaplan-Meier estimates for overall and event-free survival 5 years after transplant are 53% (95% CI, 37% to 67%) and 47% (95% CI, 33% to 60%), respectively. In a univariate analysis, patients with a normal performance status and those without constitutional ("B") symptoms at protocol entry had an improved overall and event-free survival. In a multivariate analysis, only a normal performance status remained significant. Disease progression occurred in 17 patients at an actuarial rate of 39% (95% CI; 26% to 56%) and occurred at previous sites of active disease in all but one patient; our analysis did not identify prognostic factors for progression. Toxic deaths, caused by either neutropenic sepsis or interstitial pneumonitis (IP), occurred in 12 patients (21%; 95% CI, 10% to 32%). CBV with autologous marrow support can produce durable remissions in a substantial number of patients with Hodgkin's disease considered incurable with conventional measures. Regimen refinements may even further improve the therapeutic index of BMT in this malignancy. PMID- 1919638 TI - Busulfan, cyclophosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancy. AB - Sixteen patients with poor-prognosis acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL) underwent conditioning with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BUCY-2) plus melphalan (90 or 135 mg/m2) and autologous bone marrow transplantation (AuBMT) in a phase I study. At the melphalan dose of 90 mg/m2, grade greater than or equal to 3 regimen-related toxicity (RRT) was observed in five patients (31%; 95% confidence interval [CI], 11% to 59%), with hepatic (venoocclusive disease [VOD]) and urinary (hemorrhagic cystitis) RRT being the most frequent complications. Further escalation of the melphalan dose to 135 mg/m2 was deemed excessively toxic, as three of five patients had grade greater than or equal to 3 RRT. Following this experience, 21 patients with multiple myeloma (MM) and chronic myelogenous leukemia (CML) were treated with BUCY-2 plus melphalan 90 mg/m2 and AuBMT in separate studies. Three of these patients--all with extensively pretreated MM--had grade greater than or equal to 3 RRT (14%; 95% CI, 3% to 36%); no others had grade greater than or equal to 3 RRT. Therefore, a total of eight of the 37 patients (22%; 95% CI, 10% to 38%) who received BUCY-2 plus melphalan 90 mg/m2 conditioning developed grade greater than or equal to 3 RRT; three of these patients (8%; 95% CI, 3% to 25%) died of RRT. Although limited by the relatively small number of patients, our analysis of the patients receiving this regimen showed that the presence of parameters denoting the lymphoid diagnostic group (ie, ALL, NHL, and MM), more extensive pretreatment, and/or more advanced disease status were associated with a higher incidence of grade greater than or equal to 3 RRT. Response data on the AML, ALL, and NHL patients who received BUCY-2 plus melphalan 90 mg/m2 were analyzed: three patients (all with AML in first or second remission) are leukemia-free at 3.0, 2.8, and 1.4 years after AuBMT. The actuarial 2-year event-free survival in this group is 17% (95% CI, 5% to 54%). Response data on the MM and CML patients will be reported subsequently. BUCY-2 plus melphalan at a dose of 90 mg/m2 before AuBMT produces acceptable toxicity in patients who are not heavily pretreated. A full evaluation of the antineoplastic effects of this regimen requires further study. PMID- 1919639 TI - Transfusion-associated graft-versus-host disease: historical perspectives, incidence, and current use of irradiated blood products. AB - Transfusion-associated graft-versus-host disease (TGVHD) has been reported in 131 patients as a complication of supportive treatment with an overall 90% mortality. This study was undertaken to define the historical incidence of TGVHD, its symptomatology, and mortality among affected patients by age, diagnosis, and blood product transfused. Although the use of irradiated blood products (IBPs) virtually eliminates the risk of this highly lethal complication, the use of IBPs appears variable. To ascertain current use of IBPs, questionnaires were sent to 100 pediatric and adult hematologists, oncologists, and bone marrow transplant physicians asking their perceptions about and actual use of IBPs. The results of the questionnaire, information on irradiation effects on cellular blood products, and current recommendations for irradiation of blood products are discussed. PMID- 1919640 TI - Herpes simplex virus infection in the immunocompromised cancer patient. AB - The development of infection remains a significant source of morbidity and mortality in the oncology patient. This patient population is at increased risk for infection because of alterations in cell-mediated immunity generated by the underlying neoplastic process and/or immunosuppressive therapy. Viral infection, particularly that attributable to herpes simplex virus (HSV), is being seen with increased frequency in the oncology patient. Because effective therapy is available with the early use of antiviral agents, it is important to be aware of the potential for viral infection and to recognize the signs and symptoms that are evident early in its course. An overview of HSV infection is provided here, including discussion of the virus itself, its pathogenesis, its clinical spectrum, and current prophylactic and therapeutic approaches. PMID- 1919641 TI - Burnout syndrome in the practice of oncology: results of a random survey of 1,000 oncologists. AB - Burnout, the end result of stress, can occur in any profession. We set out to determine the extent of burnout among a representative group of American oncologists. A questionnaire with 12 specific points was designed and prepared by the authors. It was mailed to 1,000 randomly selected physician subscribers to the Journal of Clinical Oncology. Five hundred ninety-eight completed surveys (60%) were returned before the cut-off date and included in the analysis. Overall, 56% of the respondents reported experiencing burnout in their professional life. No significance was found between the incidence of burnout and specialty within oncology, year medical training ended, or practice location. Significance was found, however, between type of practice and the incidence of burnout; institution- or university-based oncologists reported a lower incidence of burnout (47%) versus all other types of practice (66% burnout rate for oncology plus internal medicine, 63% for private adult oncology only, 39% for pediatric oncologists [there were too few pediatric oncologists for this rate to be significant], and 64% for others; P = .0003). Frustration or a sense of failure was the most frequently chosen (56%) description of burnout, and insufficient personal and/or vacation time was the most frequent reason (57%) chosen to explain the existence of burnout. To alleviate burnout, the majority (69%) of respondents indicated the need for more vacation or personal time. Administering palliative or terminal care, reimbursement issues, and a heavy work load were identified as contributing factors to burnout. Given the high response to the questionnaire and a 56% incidence of burnout in the surveyed population, it is concluded that further research on this issue is required. PMID- 1919643 TI - Comparison of the cytotoxic activities of cisplatin and carboplatin against glioma cell lines at pharmacologically relevant drug exposures. AB - Carboplatin has lower nephro- and neurotoxicities and better penetration into brain tissue than cisplatin. If carboplatin has comparable cytotoxicity against glioma cells, it might have a therapeutic advantage in the treatment of malignant gliomas. Using an assay of colony-forming efficiency, we compared the cytotoxicity of these two drugs in human glioma cell lines SF-126, SF-188, U87 MG, and U251-MG. The experiments were designed so that the product of in vitro drug concentration (C) and time (T) would encompass the same range of values as the C x T of the ultrafilterable platinum plasma fraction as determined by pharmacokinetic studies in man. The in vitro stability of the drugs was evaluated by measuring the cytotoxicity of aged drugs with a microculture tetrazolium assay. Cisplatin and carboplatin were both stable during the 2-h treatment. The cytotoxic activities of these drugs at clinically achievable levels of drug exposure were of the same order of magnitude. These results, in conjunction with the lower nephro- and neurotoxicities of carboplatin, the higher platinum levels in brain tissue after treatment with carboplatin, and the encouraging results of carboplatin in the clinical treatment of brain tumors that have been demonstrated in other studies, suggest that carboplatin might be preferable to cisplatin in the treatment of patients with malignant glioma. PMID- 1919644 TI - Hyperthermic potentiation of BCNU toxicity in BCNU-resistant human glioma cells. AB - Experimental evidence indicating potentiation of the cytotoxic effect of drugs at high temperatures suggests that the utilization of drug-heat combinations for gliomas of the brain might be therapeutically useful. Hyperthermia may increase the cytotoxicity of a particular drug in areas of low drug concentration/time and in cell populations resistant to the drug. We report in vitro experiments with a BCNU resistant, U-373MG, and a BCNU sensitive, U-87MG, human derived glioma cell lines under hyperthermic conditions. Temperatures equal or above 42 degrees C potentiate BCNU cell kill in both lines. The thermo-sensitizer lidocaine increases thermal cell kill but only minimally with concentrations corresponding to therapeutic plasma lidocaine levels. Within our experimental conditions, the best strategy to overcome BCNU resistance involved a combination of heat, BCNU and cis-DDP. BCNU resistant cells have no cross resistance to cis-DDP and the combination of BCNU and cis-DDP is synergistic. At modest hyperthermic conditions (42 degrees C) 99.4% BCNU resistant cells are killed by a combination of BCNU and cis-DDP at drug concentrations identical to plasma concentrations after standard IV doses. Clinical protocols using heat and drug may need to incorporate two or more drugs for optimal effects. PMID- 1919645 TI - Malignant properties of P635 glioma are independent of glial fibrillary acidic protein expression. AB - To examine the relationship between the malignant behavior of rat glioma cells and expression of the differentiation antigen glial fibrillary acidic protein (GF), we assayed the tumorigenicity and metastatic ability of P635 and its GF+ or GF- clones. We injected P635 (GF+) and clone 45 (GF-) cells intramuscularly in nude mice. Both lines formed local tumors which metastasized to lungs with equal efficiency. We then injected these lines intravenously in nude mice. Both produced experimental metastases in lungs and other organs with equal efficiency. Finally we injected P635 and several GF+ and GF- clones into the chorioallantoic membrane veins of naturally immune-deficient chick embryos and measured cell growth in embryonic liver. We again found that all clones survived and grew equally well. P635 cells are capable of extracranial growth and metastasis, two important features of the malignant phenotype. We conclude that GF in P635 is a neutral marker with respect to tumorigenicity and metastatic ability. PMID- 1919642 TI - Medulloblastoma: tumor biological and clinical perspectives. AB - Medulloblastoma is the most common central nervous system malignancy of childhood, with approximately 350 new cases seen in the United States each year. Although the low incidence of this tumor, compared with adult neoplasms such as breast or colon carcinoma, has limited laboratory and clinical research, recent studies have greatly enhanced our understanding of the biology, phenotype, genotype, and therapy of medulloblastoma. Further efforts to integrate laboratory and clinical studies of this tumor may allow design of novel therapeutic approaches resulting in enhanced disease-free survival. PMID- 1919646 TI - Isolation and characterization of microvessels from normal brain and brain tumors. AB - We describe a new technique for isolating microvessels from both brain and brain tumors. This method is relatively quick and provides a microvessel preparation free of contamination by other brain tissue. Using this method, structurally intact microvessels from normal rat brain and from a malignant rat astrocytoma were isolated and characterized with light microscopy, scanning electron microscopy and transmission electron microscopy. In contrast to microvessels derived from normal rat brain, rat astrocytoma microvessels had endothelial cells with multilayered basement membranes, extensive microvilli on the cell surfaces, and a significant increase in the number of pinocytes in the cytoplasm. Furthermore, astrocytoma microvessel endothelial cells had pleomorphic electron dense nuclei with pale perichromatin, whereas the nuclei of endothelial cells of microvessels derived from normal brain tissue were finely granular and homogeneous with characteristically electron dense perichromatin. The morphologic characteristics of the astrocytoma microvessels are similar to the histologic changes seen in astrocytoma tissue in situ, and correlate well with the known altered functions of brain tumor neovasculature. PMID- 1919647 TI - Cisplatin, ara-C and etoposide (PAE) in the treatment of recurrent childhood brain tumors. AB - Sixteen patients with recurrent childhood brain tumors were treated with intravenous cisplatin, cytosine arabinoside and etoposide (PAE), daily for three days every three to four weeks. Objective responses were observed in 6 of 15 evaluable patients and an additional six patients had stable disease for greater than 6 months. The tumor-specific response rate for astrocytoma/glioma was 3 of 7 and for medulloblastoma was 2 of 4. The mean progression-free interval was 11.0 months and the hazard rate for progression was 0.085 per patient-month of observation. The most common toxicities were neutropenia and thrombocytopenia. Clinically significant ototoxicity was identified in 7 patients. The activity of PAE chemotherapy for recurrent childhood brain tumors warrants further investigation. PMID- 1919648 TI - Corynebacterium JK: a new pathogen in ventriculostomy infections. AB - In the past decade, Corynebacterium JK has emerged as a pathogen in several distinct clinical settings, including sepsis in immunocompromised patients and prosthetic valve endocarditis. It is also recognized as a nosocomial pathogen in infections of prosthetic devices. We present a case of a patient with carcinomatous meningitis who developed a Corynebacterium JK infection of an internal ventriculostomy which was used for intraventricular chemotherapy. Treatment with systemic and intraventriculostomy vancomycin for three weeks resulted in bacteriologic resolution of the infection. Removal of the prosthetic device was not essential for cure in this patient. The clinical spectrum of infection with this organism and aspects of therapy are reviewed. As a greater awareness of the pathogenic nature of this organism develops, it is likely to be implicated as a causative agent in a variety of infections. PMID- 1919650 TI - Radioimmunoassay of glioma associated antigen in CSF and its usefulness for the diagnosis and monitoring of human glioma. PMID- 1919649 TI - Visual scotomata resulting from lupus anticoagulant in a patient with lymphoma in remission. AB - Episodic cerebro or retinovascular ischemic events without apparent cause occur in patients with cancer. We report a patient in remission from lymphoma whose multiple episodes of presumed ocular ischemia occurred in the setting of a circulating lupus anticoagulant. Symptoms resolved following therapy with Warfarin. PMID- 1919651 TI - In-vitro activity of meropenem, a new carbapenem, against imipenem-resistant Pseudomonas aeruginosa and Xanthomonas maltophilia. AB - The activity of meropenem, a new carbapenem, as well as imipenem, ceftazidime, aztreonam, tobramycin, amikacin and ciprofloxacin against 18 strains of Xanthomonas maltophilia and 23 strains of Pseudomonas aeruginosa resistant to imipenem was tested. All strains of X. maltophilia were resistant to both penems. Ceftazidime, tobramycin and ciprofloxacin were the most active antimicrobial agents against this specie. 17% of imipenem-resistant strains of P. aeruginosa were sensitive to meropenem. Ciprofloxacin, amikacin and aztreonam were the most effective agents against these strains. PMID- 1919652 TI - Enoxacin therapy for experimental pseudomonas keratitis. AB - Pseudomonas keratitis is difficult to treat and aminoglycosides, the drugs now used for this purpose, are not always effective. New drugs are thus needed to cure gentamicin resistant pseudomonas ocular infections. Enoxacin, a new quinolone, active in vitro against Pseudomonas aeruginosa, was evaluated in experimental ulcerative keratitis produced by a gentamicin resistant isolate of Pseudomonas aeruginosa in rabbits. Our study shows that enoxacin eye drops eliminated pseudomonas infection of the cornea and achieved therapeutic levels in the aqueous humor. Supplementation with parenterally given enoxacin augmented this effect. Enoxacin did not penetrate the vitreous. Enoxacin eye drops may be evaluated for their clinical usefulness in case of keratitis caused by Gram negative bacilli. PMID- 1919653 TI - Otitis externa malignum. AB - Twelve elderly diabetic patients with Pseudomonas otitis externa malignum were successfully treated with norfloxacin as monotherapy for 2-5 weeks, using 400 mg b.i.d. Patients tolerated the courses with no side effects, except some drowsiness in two patients, and all completed the course. The bacteriological and clinical cure rate was 100%, without resorting to surgery. PMID- 1919654 TI - A phase I study of cisplatinum plus 5-fluorouracil in modulation with citrovorum factor in metastatic colorectal carcinoma. AB - A phase I study of 5-fluorouracil 600 mg/m2/week and folinic acid 500 mg/m2/week on day 1 and cisplatin administered weekly on day 2 was carried out on 30 patients with metastatic colorectal carcinoma of which 20 patients were pretreated with 5-fluorouracil. The first group of patients received cisplatin at the dose of 5 mg/m2/week. Cisplatin was then escalated to 10, 15, 20, 25, 30, and 35 mg/m2/week for subsequent groups of patients. Gastrointestinal side-effects were the dose-limiting toxicity. A therapy related death was seen at the dose of 35 mg/m2/week of cisplatin. The maximally tolerated dose of cisplatin in combination with 5-fluorouracil and citrovorum factor is 20 mg/m2/week. The optimally tolerated dose of 5-fluorouracil is 400 mg/m2/week in modulation with citrovorum factor 500 mg/m2/week. The recommended doses for a phase II study are cisplatin 20 mg/m2/week, 5-fluorouracil 400 mg/m2/week, and citrovorum factor 500 mg/m2/week. PMID- 1919655 TI - Cyclophosphamide plus epidoxorubicin and 5-fluorouracil with folinic acid as a novel treatment in metastatic breast cancer: preliminary results of a phase II study. AB - Twenty consecutive patients with advanced breast cancer were treated with a combination of cyclophosphamide 600 mg/m2 i.v. on day 1, epidoxorubicin 75 mg/m2 on day 1, and 5-fluorouracil 375 mg/m2 i.v. with folinic acid 200 mg/m2 i.v. on days 1----3. The overall response rate was 60%, with 10% of patients showing a complete response with a mean duration of 11.1 + months, and 50% of patients a partial response of 7.4 + months. A stabilization of 5.2 + months was obtained in 20% of cases, while 20% of patients progressed. The most frequently observed toxicity was leukopenia, while expected mucosal toxicities were rather mild. PMID- 1919656 TI - Fluorouracil, high-dose folinic acid, low-dose alpha-2b interferon and dipyridamole in the treatment of advanced colorectal cancer. A pilot study. AB - Twenty-six patients with advanced colorectal cancer were treated with a combination based on multimodal biochemical modulation of 5-fluorouracil by means of high dose folinic acid, low-dose alpha-2b interferon and dipyridamole. The overall response rate was 42% (95% confidence intervals = 23%. 61%) with four complete remissions (15%). The median duration of response was 9 months and the median survival for responders was 15 months (all patients = 12 months). Toxic side effects included oral mucositis (grade III-IV = 38%) and a generally mild flu-like syndrome. This regimen seems active and safe enough to be compared with the combination of fluorouracil and high-dose folinic acid. PMID- 1919657 TI - Platinum-based induction chemotherapy followed by radiation as definitive treatment for patients with locally advanced cancer of the oral cavity, oropharynx and hypopharynx. A retrospective analysis of 32 cases. AB - Thirty-two patients with locally advanced cancer of oral cavity, oropharynx and hypopharynx were treated with three cycles of platinum-based induction chemotherapy followed by radiation therapy. After completion of the combined treatment 50% of the patients were in complete response (CR) and 28% in partial response (PR). So far, 24 patients have died. Local progression occurred in 20 patients. Survival is 29% at 24 months. Seven (22%) patients remain alive and have been disease-free for 22-59 months. In conclusion, induction chemotherapy followed by radiation therapy may omit radical surgery, without compromising survival, in some patients with locally advanced cancer of the oral cavity, oropharynx and hypopharynx. PMID- 1919659 TI - Intensive chemotherapy with cisplatin, mitoxantrone, methotrexate and vincristine in metastatic breast cancer. AB - Eleven patients (pts) with advanced refractory breast carcinoma were treated with combination chemotherapy (Planovin) including mitoxantrone 10 mg/m2 on day 1, cisplatin 60 mg/m2 on days 1-2, methotrexate 200 mg/m2 on day 15, vincristine 2 mg on day 15, leucovorin 15 mg/m2 on days 15-16 every 3 weeks. Five patients (41%) achieved an objective response with one complete regression. The median duration of response was 4.5 months and the median duration of survival was 8 months. Drug related toxicity consisted mainly of leukopenia (8 pts), nausea and vomiting (6 pts), anemia (7 pts) and thrombocytopenia (4 pts). PMID- 1919658 TI - Primary lymphoma of bone: long term results in patients treated with vincristine- adriamycin--cyclophosphamide and local radiation. AB - Primary lymphoma of bone (PLB) is an unusual but well-recognized extranodal presentation of non-Hodgkin's lymphoma. In most series treatment with radiotherapy alone results in a cure rate of approximately 40%. Between January 1972 and December 1982, 26 patients with biopsy proven PLB were treated at the Rizzoli Institute with radiotherapy (4000-5,500 rad) and chemotherapy (vincristine, cyclophosphamide and adriamycin). The minimal clinical staging included complete blood cell counts and serum chemistries, bone radiography, full lung tomography, isotope bone scan, bone marrow biopsy and bipedal lymphoangiograms. At a median follow-up of 13 years (8.5-18.5) there were only three relapses (2 cases of meningeal involvement and 1 recurrence in another bone). No local recurrences nor second tumor in the irradiated field were observed. We conclude that the addition of chemotherapy to radiotherapy results in an excellent cure rate for patients with PLB. PMID- 1919660 TI - Effect of anoxia on intracellular and extracellular potassium activity in hypoglossal neurons in vitro. AB - 1. A brain slice preparation was used to study the hypoglossal (XII) neuronal response to anoxia. Both intra- and extracellular potassium activities (K+i,K+o) were measured by the use of ion-selective microelectrodes, and K+ flux was assessed by the use of pharmacologic blockers. 2. Extracellular recordings showed that a short period of anoxia (4 min) induced an increase in K+o of 26.4 +/- 7.5 mM (mean +/- SD, n = 20) in the XII nucleus of adult rats. 3. Intracellular recordings (n = 31) in XII neurons showed a substantial decrease in K+i during anoxia. Fourteen neurons were analyzed in detail and these showed that XII neurons depolarized to -25.3 +/- 7.7 mV, whereas K+i dropped from 93.6 +/- 14.9 to 32 +/- 9.0 mM. These results strongly suggested that K+ is lost from XII neurons during anoxia. 4. Although the extracellular space (ECS) shrank by approximately 50% during anoxia, the possibility that the increase in K+o and decrease in K+i were mainly caused by shrinkage of the ECS and swelling of intraneuronal space was excluded to a great degree because the changes in K+i and K+o during anoxia were relatively very large. 5. To study the mechanisms by which K+ is lost from XII neurons, we used several pharmacologic blockers. High concentration of ouabain (10 mM) and strophanthidin (80 microM) increased K+o from baseline (3-4 mM) to 40.9 +/- 2.5 mM (n = 6) but did not abolish an additional anoxia-induced increase in K+o, suggesting that mechanisms other than Na(+)-K(+)-adenosine triphosphatase inhibition were also responsible for the anoxia-induced K+ leakage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919661 TI - Responses of olfactory receptor cells of spiny lobsters to binary mixtures. I. Intensity mixture interactions. AB - 1. Neural coding of chemical mixtures was studied with the use of the peripheral olfactory system of the spiny lobster. The occurrence of mixture interactions (i.e., where the observed response to a mixture deviates significantly from the expected response) in individual cells and the effect of such mixture interactions on the coding of odorant intensity by populations of cells were examined. 2. Extracellular recordings of spiking activity of 98 primary olfactory receptor cells in the antennules were measured in response to seven compounds [adenosine-5'-monophosphate (AMP), betaine (Bet), L-cysteine (Cys), L-glutamate (Glu), ammonium chloride (NH4), DL-succinate (Suc), and taurine (Tau)] and their binary mixtures. To identify mixture interactions, observed responses to a range of concentrations of a binary mixture were compared with the predicted responses based on three mathematical models: a single receptor model, which assumes that the two compounds of a mixture bind to the same receptor site; a multiple receptor model, which assumes that the two compounds bind to two independent receptor sites; and a mixed composition receptor model, which incorporates our current state of knowledge of transduction processes in olfactory receptor cells of spiny lobsters. 3. Mixture interactions in individual cells were common: statistically significant mixture interactions were observed in 25% of the possible cases (Fig. 5). Suppression was much more common than enhancement. 4. Mixture interactions had significant effects on the absolute response magnitudes for a population of cells, which could be used as the neural code for stimulus intensity in this system. These effects are called intensity mixture interactions (Figs. 6-11). Intensity mixture interactions occurred for approximately 50% of the binary mixtures and were almost exclusively suppression (Figs. 12 and 13). The intensity mixture interactions were concentration independent. 5. The results suggest that mixture interactions in individual olfactory cells can result in intensity mixture interactions in the neuronal population such that there is a decrease in sensitivity to binary mixtures relative to what is expected based on the responses to individual components of the mixtures. PMID- 1919662 TI - Phase-dependent modulations of anticipatory postural activity during human locomotion. AB - 1. The ability of the CNS to coordinate several motor tasks was studied in humans walking on a treadmill while pulling on a handle. Subjects were instructed to respond to an audio signal that was presented in different phases of the step cycle. Electromyograph (EMG) and movements were recorded from the left arm and leg. 2. The activity of the arm muscle was preceded by postural activity in the leg muscles. The pattern of the anticipatory postural activity differed in the various phases of the step cycle. Lateral gastrocnemius and hamstring muscles were activated during responses occurring in the early support phase whereas tibialis anterior and quadriceps muscles were activated when the pull was exerted during the late support phase and during the swing phase. In the middle of the support phase the combination of both muscle activity was present. 3. The temporal sequencing and the spatial distribution of the anticipatory muscle activity changed gradually. Early during the support phase the hamstring muscles were activated before the gastrocnemius muscle, whereas the order was reversed during midstance. The EMG amplitude of the hamstring and gastrocnemius muscles was largest in the beginning of the support phase and then gradually decreased, whereas the amplitude of the tibialis anterior and quadriceps muscles increased during the later parts of the support phase. 4. The anticipatory responses to pulls exerted during the first part of the support phase reduced the ankle flexion during the single support phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919663 TI - Responses of olfactory receptor cells of spiny lobsters to binary mixtures. II. Pattern mixture interactions. AB - 1. The effect of mixture interactions in individual olfactory receptor cells of the spiny lobster on neural coding of odorant quality of binary mixtures and their components is examined in this paper. Extracellular responses of 98 olfactory receptor cells in the antennules of spiny lobsters to seven compounds [adenosine-5'-monophosphate (AMP), betaine (Bet), L-cysteine (Cys), L-glutamate (Glu), ammonium chloride (NH4), DL-succinate (Suc), taurine (Tau)] and their binary mixtures were recorded, and mixture interactions in individual olfactory receptor cells were identified. 2. Coding of odorant quality was evaluated by examining across neuron patterns (ANPs)--the relative response magnitudes across neuronal populations. ANPs are a feature of the neuronal population response and are a possible concentration-independent code of odorant quality in this system, as indicated by previous studies and present results. 3. For most binary mixtures the diversity of types and degrees of mixture interactions across the individual cells of a population of cells resulted in ANPs for each mixture to be different from the ANPs for the components of the mixture and different from the ANP predicted for the mixture from the responses to the components (Figs. 2-10). These effects are called pattern mixture interactions (PMIs). PMIs occurred for most binary mixtures, even those that did not produce statistically significant intensity mixture interactions (IMIs) for this same population of cells. 4. The results suggest that PMIs can influence coding of stimulus quality, in some cases by causing an improvement of the contrast between the quality of mixtures and some of their components. PMID- 1919664 TI - Neuronal activity in the primary somatosensory cortex in monkeys (Macaca mulatta) during active touch of textured surface gratings: responses to groove width, applied force, and velocity of motion. AB - 1. In a descriptive survey of primary somatosensory cortex (SI) responses during active touch, two monkeys (Macaca mulatta) were trained to stroke their fingertips over pairs of gratings with constant ridge (250 microns) and varying groove (500-2,900 microns) width (roughness) and to identify the smoother (smaller groove). Speed of hand motion and applied force level during the stroke were monitored and recorded. Transdural single-unit recordings were obtained from areas 3b and 1 of SI while animals performed the task. 2. The statistical sample consisted of 164 single units. Most cells in the sample responded in some fashion during the stroke, including brief increased or decreased activity to 1-mm ridges (touch strips) placed between surface pairs and at ends of each block to serve as touch sensors. These peristroke response patterns were described briefly. Most cells (153/164) responded to grating contact. Three types of responses to groove width were characterized. 1) Response was proportional to groove width in many cells. There was a vigorous response to roughest and none to smoothest surface. Mean firing rates for these cells appeared linearly related to groove width. 2) Graded responses were seen with smaller response differences to the same groove width range as in 1. Responses of some cells of types 1 and 2 were uncorrelated with variations in applied force and velocity of stroke. 3) There were inverse responses to groove width. Greater responses occurred during contact with smoother surfaces. 3. Many cells were influenced by a combination of changes in groove width, force, and/or velocity. Activity of a small sample of cells in area 1 with slowly adapting (SA) response properties was an almost exclusive positive function of variations in force level. Unlike SAs in 3b, responses of these cells were uncorrelated with alterations in groove width or stroke velocity. Velocity effects were almost always associated with response to groove width. Positive velocity cells coded temporal period. Significant velocity effects were not evident in graded or inverse graded cells. Negative force and velocity effects were due to shifts in behavioral strategy. Periodicity related to the spatial period of the grating was found in autocorrelograms of a small number of cells. Finally, responses of some cells were unaffected by changes in groove width, force, or velocity. Some of these were affected by contact with touch strips. Others responded in undifferentiated fashion to the stroke, and their function remains unresolved. Overall, there was a continuum of response patterns. Subgroups of cells were not distinct.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919665 TI - Coding visual images of objects in the inferotemporal cortex of the macaque monkey. AB - 1. The inferotemporal cortex (IT) has been thought to play an essential and specific role in visual object discrimination and recognition, because a lesion of IT in the monkey results in a specific deficit in learning tasks that require these visual functions. To understand the cellular basis of the object discrimination and recognition processes in IT, we determined the optimal stimulus of individual IT cells in anesthetized, immobilized monkeys. 2. In the posterior one-third or one-fourth of IT, most cells could be activated maximally by bars or disks just by adjusting the size, orientation, or color of the stimulus. 3. In the remaining anterior two-thirds or three-quarters of IT, most cells required more complex features for their maximal activation. 4. The critical feature for the activation of individual anterior IT cells varied from cell to cell: a complex shape in some cells and a combination of texture or color with contour-shape in other cells. 5. Cells that showed different types of complexity for the critical feature were intermingled throughout anterior IT, whereas cells recorded in single penetrations showed critical features that were related in some respects. 6. Generally speaking, the critical features of anterior IT cells were moderately complex and can be thought of as partial features common to images of several different natural objects. The selectivity to the optimal stimulus was rather sharp, although not absolute. We thus propose that, in anterior IT, images of objects are coded by combinations of active cells, each of which represents the presence of a particular partial feature in the image. PMID- 1919667 TI - Interactions between visceral and cutaneous nociception in the rat. I. Noxious cutaneous stimuli inhibit visceral nociceptive neurons and reflexes. AB - 1. Numerous studies have demonstrated that neural, behavioral, and reflex responses to a nociceptive test stimulus are inhibited by conditioning nociceptive stimuli; this inhibition has supraspinal, intraspinal, and segmental components. The general phenomenon is defined here as nocigenic inhibition. The present study of nocigenic inhibition documents that noxious cutaneous pinch and heat, used as conditioning stimuli, inhibit neuronal and reflex responses evoked by a noxious visceral stimulus, colorectal distension. 2. A total of 196 dorsal horn neurons were examined: 110 were short latency-abrupt (SL-A) neurons that were excited at short latency by colorectal distension and returned to baseline activity abruptly after termination of the distending stimulus, and 86 were short latency-sustained (SL-S) neurons that also were excited by colorectal distension at short latency, but demonstrated after-discharges for 4-240 s after termination of the distending stimulus. All SL-A and SL-S neurons studied had convergent cutaneous receptive fields. 3. The spontaneous activities of 100% of the 110 SL-A neurons tested were inhibited by greater than 25% by noxious pinch in sites distant from their convergent cutaneous receptive fields. In both anesthetized, intact, and spinalized rats, noxious conditioning pinch or noxious conditioning heat significantly reduced responses of SL-A neurons during noxious test colorectal distension. The magnitude of this nocigenic inhibition was graded with the intensity of the noxious conditioning stimulus. Noxious conditioning tail heating produced a parallel shift to the right in stimulus-response functions relating neuronal responses to the intensity of colorectal distension (20-100 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919666 TI - Neurogenic hyperalgesia: psychophysical studies of underlying mechanisms. AB - 1. Psychophysical studies were made, in humans, of the sensory characteristics and underlying mechanisms of the hyperalgesia (often termed "secondary hyperalgesia") that occurs in uninjured skin surrounding a local cutaneous injury. The hyperalgesia was characterized by lowered pain thresholds and enhanced magnitude of pain to normally painful stimuli. The "injury" was produced by a single intradermal injection of 10 microliters of 100 micrograms of capsaicin, the algesic substance in hot chili peppers. 2. On injection of capsaicin into the volar forearm, the subjects experienced intense burning pain, accompanied immediately by the formation of three areas of hyperalgesia surrounding the injection site. The largest mean area (55 cm2) was hyperalgesic to a normally painful punctate stimulation of the skin. Nested within this was an area of tenderness to gentle stroking (38 cm2) and a much smaller area of hyperalgesia to heat (2 cm2). An area of analgesia to pinprick, approximately 4 mm in diameter and centered on the injection site, developed within minutes and typically disappeared within 24 h. The hyperalgesia to heat and to stroking disappeared within 1-2 h, whereas the hyperalgesia to punctate stimuli, although gradually decreasing in area, lasted from 13 to 24 h. 3. The radial spread of the mechanical hyperalgesia (to punctate and stroking stimuli) away from the injury was dependent on neural activity and not produced, for example, by algesic substances transported away from the injury. The injection of capsaicin into a small area of anesthetized skin did not produce hyperalgesia in the surrounding, unanesthetized skin. Also, the hyperalgesia in normal skin readily crossed a tight arm band that blocked the circulation of blood and lymph. 4. The spread of mechanical hyperalgesia away from the injury was peripherally mediated via cutaneous nerve fibers because it was blocked by a thin mediolateral strip of cutaneous anesthesia placed 1 cm away from the capsaicin injection site. Hyperalgesia developed normally on the capsaicin side of the strip but not on the other side. 5. Heat stimulation of the skin that produced pain that was equivalent in magnitude and time course to that produced by an injection of capsaicin (10 micrograms) resulted in much smaller areas of mechanical hyperalgesia. It was postulated that there exist special chemosensitive primary afferent nerve fibers that are more effective in producing mechanical hyperalgesia than are the known thermo- and mechanosensitive nociceptive nerve fibers. 6. Once developed, the mechanical hyperalgesia became only partially dependent on peripheral neural activity originating at the site of injury.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919668 TI - Neurogenic hyperalgesia: the search for the primary cutaneous afferent fibers that contribute to capsaicin-induced pain and hyperalgesia. AB - 1. A local cutaneous injury can produce primary hyperalgesia within the injured area and secondary hyperalgesia in the normal surrounding skin. An intradermal injection of capsaicin in humans causes intense pain and hyperalgesia to heat and to mechanical stimuli in the surrounding skin. Psychophysical studies in humans supported the conclusions that the hyperalgesia was predominantly the secondary type and depended on one set of neurons sensitizing another ("neurogenic hyperalgesia") and that the latter set of neurons is located in the central and not the peripheral nervous system. To further test this hypothesis and to search for peripheral neural mechanisms contributing to the pain and neurogenic hyperalgesia from a local injury, we performed neurophysiological experiments in the monkey (Macaca fascicularis) and recorded the responses of cutaneous primary afferent fibers to an intradermal injection of capsaicin and to mechanical and heat stimuli delivered before and after the injection. 2. Most C- and A-fiber mechanoheat-sensitive nociceptive afferent fibers (CMHs and AMHs, respectively) responded too weakly or transiently to capsaicin to account quantitatively for the magnitude of capsaicin pain. Of the known primary afferents tested with capsaicin injections, only the responses of heat-selective nociceptors could potentially account for the pain measured psychophysically in the human. In addition, a novel type of primary afferent--tentatively termed "chemonociceptive" -may have contributed as well. 3. Nociceptive fibers did not become sensitized to either mechanical or heat stimulation after an injection of capsaicin either outside, adjacent to, or inside the receptive field (RF); any changes that occurred could not explain the hyperalgesia to mechanical or heat stimuli observed in humans. 4. The depressed responsiveness ("desensitization") of both myelinated and unmyelinated nociceptive fibers in the monkey to heat and/or mechanical stimulation of the injection site after capsaicin was injected inside their RFs correlated with the analgesia observed at the capsaicin injection site in the human. 5. Capsaicin, topically applied to the RF in a vehicle of dimethyl sulfoxide or alcohol, excited CMHs and AMHs and enhanced the responses of some of these fibers to heat and/or to stroking the skin. In some cases, similar results were produced by the vehicle alone. However, capsaicin and not the vehicle lowered the thresholds of some CMHs to heat. Thus the sensitization of CMHs contributes to the primary hyperalgesia known to occur within the area of skin directly exposed to topically applied capsaicin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919669 TI - Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract neurons. AB - 1. The contribution of activity in spinothalamic tract (STT) neurons to the pain and neurogenic hyperalgesia produced by an intradermal injection of 100 micrograms of capsaicin was investigated. Electrophysiological responses of identified STT neurons recorded in anesthetized monkeys were compared with psychophysical measurements of pain and hyperalgesia obtained in humans using identical stimuli. 2. Magnitude estimates of pain in humans were obtained after an injection of capsaicin or the vehicle. Capsaicin produced immediate burning pain that was most intense within 15 s after injection and then declined over the next 10-30 min. The vehicle produced no pain. 3. Cutaneous hyperalgesia to gentle stroking (allodynia) and also hyperalgesia to punctate stimulation developed in a wide area surrounding the capsaicin injection. Within this area, magnitude estimates of pain produced by a punctate stimulus (von Frey type with force of 225 mN) increased over preinjection values by an average of sixfold at test sites, 1, 2, and 3 cm away from the injection site. At the capsaicin injection site, magnitude estimates of pain in response to punctate simulation typically remained the same or were decreased. 4. After capsaicin, but not vehicle, the mean heat pain thresholds were lowered from approximately 45 degrees C before injection to 34 degrees C after, but only in the immediate vicinity of the injection site. At a site located 2 cm away, the thresholds were not significantly altered. Similarly, magnitude estimates of pain produced by suprathreshold heat stimuli were increased after capsaicin only at the injection site. 5. STT neurons were classified as high-threshold (HT) or wide-dynamic-range (WDR) cells according to responses evoked by graded cutaneous mechanical stimulation. An intradermal injection of capsaicin excited 4 of 7 HT cells and 10 of 12 WDR cells. The discharge rates of STT neurons correlated in time course with the magnitude estimates of pain in humans. The correlation was considerably better for WDR than for HT neurons, suggesting a predominant contribution of WDR neurons to the pain from capsaicin. 6. Capsaicin significantly increased the responses of HT neurons (9-fold) and the responses of WDR neurons (2-fold) to stroking the skin within the receptive field. Similar increases in responses to a standard punctate stimulus were observed at test sites, 1, 2, and 3 cm away from the injection site. After injection of vehicle, the responses to punctate stimulation increased by a mean of only 1.2- and 1.4-fold for HT and WDR neurons, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919670 TI - Responses of single facial taste fibers in the sea catfish, Arius felis, to amino acids. AB - 1. Taste buds in catfish are found not only within the oropharyngeal cavity, as in mammals, but are also located along the external body surface of the animal from the barbels and lips to the caudal fin. Because these taste buds are innervated by the facial (cranial VII) nerve, the extraoral taste system of catfish is analogous to the mammalian taste system of the anterior two-thirds of the tongue, which contains taste buds innervated by the chorda tympani nerve, and of the soft palate and nasoincisor ducts, which contain taste buds innervated by the greater superficial petrosal nerve. 2. The majority of information concerning the specificity of individual taste fibers in vertebrates has been obtained primarily in mammals to stimuli representing the four basic human taste qualities (i.e., salty, sweet, sour, and bitter). In the present report, we examine the evidence for gustatory fiber types within the stimulus class of amino acids, compounds known to be especially relevant gustatory stimuli for catfish and other teleosts. 3. Action potentials were recorded from 60 individual facial taste neurons obtained from 28 sea catfish (Arius felis). Stimuli were 10(-4) M concentrations of L-alanine, D-alanine, glycine, L-proline, L-histidine, and L arginine, compounds selected from an original stimulus list of 28 amino acids. Responses were quantified as the number of action potentials evoked at various time intervals from the first 0.5 s up to 10 s of response time. 4. The spontaneous activity of 42 fully characterized neurons was 0.8 +/- 2.1 SD spikes/3 s. The average rate of spike discharge increased 50-fold during stimulation with the most effective amino acid (42 +/- 31 spikes/3 s, mean +/- SD). The majority of the sampled neurons were not narrowly tuned to the amino acid stimulants tested (mean breadth of responsiveness, H = 0.60; range 0-0.95). 5. Hierarchical cluster analysis of the fully characterized neurons identified two large and two small groups of cells. The largest group (n = 22) of neurons was stimulated most by L-alanine and glycine; the other large group (n = 17) was stimulated most by D-alanine. For this latter group, the response to glycine was relatively low, whereas the responses to L-alanine varied from 0 to nearly 100% of the D-alanine response.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919671 TI - Opposing effects of 5-hydroxytryptamine on two types of medullary inspiratory neurons with distinct firing patterns. AB - 1. Activity of inspiratory neurons was recorded extracellularly from the caudal portion of the nucleus ambiguous (0-3.5 mm rostral to the obex) in decerebrated, spontaneously breathing cats. Using a micropressure ejection method, we tested the responsiveness of the inspiratory neurons to direct applications of serotonin (5-HT) and noradrenaline (NA) in comparison with applications of glutamate and control artificial cerebrospinal fluid (ACSF) by means of a multibarreled micropipette. 2. We made detailed examinations of 52 inspiratory neurons that were excited by glutamate but did not react to control ACSF. Those inspiratory neurons were further classified into two subgroups based on the differences in firing patterns: inspiratory neurons with an augmenting firing pattern ["augmenting I units" (22/52)] and inspiratory neurons with a decrementing firing pattern ["decrementing I units" (30/52)]. 3. Although application of NA produced predominantly inhibitory effects on both the decrementing (22/30) and augmenting I units (20/22), application of 5-HT resulted in distinct or opposing effects on these two types of inspiratory neurons: the decrementing I units (25/30, 83%) were excited by 5-HT, whereas the augmenting I units (17/22, 77%) were inhibited by 5-HT. 4. The excitation of the decrementing I units with 5-HT was characterized by a long onset-latency of response and a prolonged recovery process. The increase in firing rate occurred not only during the inspiratory active phase but also during the expiratory phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919672 TI - Interactions between visceral and cutaneous nociception in the rat. II. Noxious visceral stimuli inhibit cutaneous nociceptive neurons and reflexes. AB - 1. Nocigenic inhibition is the inhibition of neural, behavioral, or reflex responses to a nociceptive test stimulus produced by another, conditioning, nociceptive stimulus. The present study examines whether a natural noxious visceral stimulus, colorectal distension, used as a conditioning stimulus would inhibit neuronal or reflex responses to noxious cutaneous stimuli. Segmental effects of colorectal distension have been previously characterized; hence conditioning effects of colorectal distension on stimuli applied at sites distant (heterosegmental effects) and adjacent (perisegmental effects) to those areas of the spinal cord that receive the greatest afferent input from the colon were examined. The conditioning effects of colorectal distension were compared with those of noxious pinch. 2. Heterosegmental effects of colorectal distension were studied in 129 neurons located in the area of the trigeminal nucleus caudalis and cervical spinal dorsal horn. Steady-state activity (spontaneous activity or activity evoked by sustained pressure) of 106 of 129 trigeminal-cervical dorsal horn neurons was inhibited by both noxious colorectal distension (100 mmHg, 20 s) and noxious pinch of the tail; all neurons inhibited by colorectal distension were also inhibited by noxious pinch. Inhibition was graded with the intensity of the distending stimulus. The class 2-class 3 classification system (neurons excited by nonnoxious and noxious or only by noxious cutaneous stimuli, respectively) was roughly predictive of susceptibility to nocigenic inhibition, because 74 of 75 class 2 neurons tested were inhibited by noxious colorectal distension or noxious pinch and only 32 of 54 class 3 neurons were similarly inhibited. Five neurons were excited by colorectal distension, all of which were class 3 neurons. 3. Perisegmental effects of colorectal distension were observed in 100 L3-L5 spinal dorsal horn neurons. The spontaneous activities and responses during noxious test heating of the glabrous skin of the hindpaw of these neurons were affected in the same way by noxious (conditioning) colorectal distension. All neurons inhibited by colorectal distension (51 class 2 and 8 class 3 neurons) were also inhibited by noxious pinch of the nose or forepaw. The magnitude of the nocigenic inhibition of responses during heating of the hindpaw was graded with the intensity and duration of the noxious conditioning colorectal distension, was a function of the number of preceding distensions given to the rat, and outlasted the distending stimulus. Conditioning colorectal distension also produced a parallel shift to the right in stimulus-response functions relating responses of neurons to the intensity of the noxious test stimulus (42-50 degrees C).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919673 TI - Discharge patterns of human C-fibers induced by itching and burning stimuli. AB - 1. The aim of this investigation was to study the peripheral neural mechanisms of the C-fiber-mediated modalities of burning pain and itch by the use of microneurography of human unmyelinated afferents. 2. Sixteen stable recordings of single C-fibers and 6 multiunit recordings were obtained from the superficial radial nerves of volunteers. All units were excited by stimulating their receptive fields with von Frey bristles (range 10-600 mN), and all but four units were also driven by radiant heat stimulation. 3. Histamine was iontophoretically applied to the receptive fields of these units for 20 or 30 s and was found to provoke itching sensations lasting several minutes, together with wheal and flare responses. Subsequently a solution containing 20 or 30% mustard oil was applied to the receptive field of the respective unit, which provoked a sensation of burning pain. 4. One-half of the units were excited by histamine, and the median discharge rates derived from interspike intervals ranged from approximately 0.1 to 0.8 Hz. Mustard oil-induced activity was observed in all histamine-sensitive units and also in three single units and in one multiunit recording that revealed no histamine response. Median interval-derived discharge rates ranged from 0.2 to 1.2 Hz. 5. Analysis of the interspike interval distribution and of the autocorrelation function derived from the chemically induced discharges of single units provided no evidence for an encoding of itch and burning pain in different discharge patterns of units responding to histamine and to mustard oil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919674 TI - Long-term optical recording of patterns of electrical activity in ensembles of cultured Aplysia neurons. AB - 1. Left upper quadrant (LUQ) cells isolated from the abdominal ganglion of Aplysia were maintained in culture to study how the cellular and synaptic properties of individual neurons contribute to the generation of patterns of electrical activity by neuronal ensembles. 2. Conventional microelectrodes were used to examine the spiking characteristics of individually cultured LUQ cells in vitro and to characterize their synaptic interactions. 3. In vitro, in contrast to in situ, LUQ neurons innervate other LUQ neurons. Intracellular recordings from pairs of LUQ cells showed that the prevalent type of postsynaptic potential was purely inhibitory. The other type of response was a dual-action postsynaptic potential, with inhibition followed by a delayed, slow excitation. 4. We established a set of criteria for the use of multiple-site optical recording techniques, in combination with impermeant probes of membrane potential, to observe the patterns of electrical activity generated by ensembles of co-cultured LUQ cells. 5. The spiking activity of individual cells within the neuronal ensembles was detected by means of the change in optical absorption of cells that were vitally stained with the dye RH155. The change in absorption was typically delta A congruent to 4 X 10(-4) per spike. We achieved a signal-to-noise (peak-to peak) ratio of approximately 10 for a 50 X 50-microns photodetector field and an incident intensity of approximately 10 mW/cm2, close to the theoretical limit. 6. These conditions permitted, for the first time, continuous optical recording from cultured neurons for periods of up to 3 h with no discernible photodynamic damage or photobleaching. This long-term optical recording permitted examination of the different patterns of electrical activity generated by individual neuronal ensembles under several different experimental conditions. 7. An elaborate tracery of regenerated neurites present in these cultures resulted in individual photodetectors recording simultaneously the activity of multiple neurons. We reconstructed the temporal firing patterns for individual neurons within ensembles even with all the neurons active simultaneously and determined the functional connections in the ensemble by analyzing the temporal relationships between firing patterns of individual neurons. Excitatory as well as inhibitory functional interactions could be observed within the neuronal ensemble, the latter after the tonic activity of the neurons was increased by reducing the extracellular [Mg2+]. 8. Examination of the optical data from ensembles constructed from identified cells having characteristic physiological responses allowed us to address the question of how cellular and synaptic properties affect the patterns of electrical activity generated by neuronal ensembles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919675 TI - Discrimination performance of single neurons: rate and temporal-pattern information. AB - 1. A new method of measuring the performance of neurons in sensory discrimination tasks was developed and then applied to single-neuron responses recorded in the auditory nerve of chinchilla and in the striate visual cortex of cat. 2. Most previous methods of measuring discrimination performance have employed decision rules that involve comparing the total counts of action potentials (spikes) produced by two different stimuli. Such measures ignore response pattern and hence may not reflect all the information transmitted by a neuron. The proposed method attempts to measure all (or most) of the transmitted information by constructing descriptive models of the neuron's response to each stimulus in the discrimination experiment; these descriptive models consist of measured probability distributions of the spike counts in small time bins. The measured probability distributions are then used to define an optimal decision rule (an ideal observer) for discriminating the two stimuli. Finally, discrimination performance is measured by applying this decision rule to novel presentations of the same two stimuli. 3. Intensity and temporal-phase discrimination were measured for three neurons in the auditory nerve of chinchilla. The discrimination stimuli were low-frequency pure tones of 70-ms duration. Intensity thresholds were found to be 5-20 dB lower at low intensities using the new pattern method compared with the traditional counting method. The pattern method led to better performance because it utilized both rate and temporal pattern information. Phase discrimination performance using the counting method was at chance because the average spike rate did not change with phase. On the other hand, using the pattern method, phase discrimination thresholds were found to decrease with intensity, often reaching values equivalent to 30-40 microseconds of temporal offset. These thresholds are as good as or better than behavioral thresholds in chinchilla. 4. Contrast and temporal-phase discrimination were measured for three neurons in the striate visual cortex of cat. The discrimination stimuli were drifting sine-wave gratings of 100- to 160-ms duration. Contrast discrimination functions measured by the pattern method and the counting method were found to be essentially identical. Phase discrimination using the counting method was at chance. However, using the pattern method, phase thresholds were found to decrease with contrast, reaching values equivalent to 7 ms of temporal offset for the two simple cells. 5. Our results suggest that temporal response pattern carries substantial information for intensity and phase discrimination in the auditory nerve and for phase discrimination in the striate visual cortex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919676 TI - Cortical somatosensory evoked potentials. I. Recordings in the monkey Macaca fascicularis. AB - 1. The anatomic generators of somatosensory evoked potentials (SEPs) to median nerve stimulation in the 10- to 30-ms latency range were investigated in monkeys (Macaca fascicularis) by means of cortical-surface and laminar recordings. 2. Three groups of SEPs evoked by stimulation of the contralateral median nerve were recorded from the hand representation area of sensorimotor cortex: P10-N20, recorded anterior to the central sulcus (CS); N10-P20, recorded posterior to the CS; and P12-N25, recorded near the CS. These potentials were similar in morphology and surface distribution whether the animal was awake or anesthetized. 3. P10-N20 exhibited a polarity inversion to N10-P20 across the CS, both in cortical-surface recordings and in laminar recordings within cortex and white matter of motor and somatosensory cortex. In contrast, P10-N20 and N10-P20 did not exhibit polarity inversion in recordings from the surface and white matter of the crowns of motor and somatosensory cortex, respectively. These results strongly suggest that these potentials are produced by a tangential generator located in the posterior wall of the CS, primarily in area 3b of somatosensory cortex. 4. P12-N25 was largest over the hand area of somatosensory cortex and showed polarity inversion across the crown of somatosensory cortex but not across the crown of motor cortex or across the walls of the CS, suggesting that P12-N25 is due to a radially oriented generator located in areas 1 and 2 of somatosensory cortex. 5. P10-N20 and P12-N25 are thought to be equivalent to the "primary evoked response" recorded from somatosensory cortex of other mammals. 6. These results are very similar to those obtained in human cortical-surface recordings and demonstrate that the monkey P10-N20, N10-P20, and P12-N25 potentials correspond to the human P20-N30, N20-P30, and P25-N35 potentials, respectively. The only appreciable difference in human and monkey SEPs is that the monkey P12 N25 appears to be generated in areas 1 and 2, whereas the human P25-N35 appears to be generated only in area 1. 7. There was no evidence of locally generated activity in areas 3a and 4. PMID- 1919677 TI - Cortical somatosensory evoked potentials. II. Effects of excision of somatosensory or motor cortex in humans and monkeys. AB - 1. To clarify the generators of human short-latency somatosensory evoked potentials (SEPs) thought to arise in sensorimotor cortex, we studied the effects on SEPs of surgical excision of somatosensory or motor cortex in humans and monkeys. 2. Normal median nerve SEPs (P20-N30, N20-P30, and P25-N35) were recorded from the cortical surface of a patient (G13) undergoing a cortical excision for relief of focal seizures. All SEPs were abolished both acutely and chronically after excision of the hand area of somatosensory cortex. Similarly, excision of the hand area of somatosensory cortex abolished corresponding SEPs (P10-N20, N10-P20, and P12-N25) in monkeys. Excision of the crown of monkey somatosensory cortex abolished P12-N25 while leaving P10-N20 and N10-P20 relatively unaffected. 3. After excision of the hand area of motor cortex, all SEPs were present when recorded from the cortical surface of a patient (W1) undergoing a cortical excision for relief of focal seizures. Similarly, all SEPs were present in monkeys after excision of the hand area of motor cortex. 4. Although all SEPs were present after excision of motor cortex in monkeys, variable changes were observed in SEPs after the excisions. However, these changes were not larger than the changes observed after excision of parietal cortex posterior to somatosensory cortex. We concluded that the changes were not specific to motor cortex excision. 5. These results support two major conclusions. 1) Median nerve SEPs recorded from sensorimotor cortex are produced by generators in two adjacent regions of somatosensory cortex: a tangentially oriented generator in area 3b, which produces P20-N30 (human) and P10-N20 (monkey) [recorded anterior to the central sulcus (CS)] and N20-P30 (human) and N10-P20 (monkey) posterior to the CS; and a radially oriented generator in area 1, which produces P25-N35 (human) and P12-N25 (monkey) recorded from the postcentral gyrus near the CS. 2) Motor cortex makes little or no contribution to these potentials. PMID- 1919678 TI - A new approach of brain tumors: the cytogenetic study. AB - Cytogenetic studies of brain tumors in adults have made it possible to determine specific chromosomal abnormalities and to detect a high incidence of gene amplification related to these abnormalities. Data from the literature and our own results show frequent numerical deviations in glioblastomas, such as gain of chromosome 7, but also 19, 20 and X, loss of certain chromosomes: monosomies 6, 14 and 22. Most of the structural abnormalities are deletions involving the chromosomal regions 1p, 6q, 7q and 9p, and the presence of double-minutes (DMs), the latter being the chromosomal expression of EGFR gene amplification. Cytogenetic analysis of meningiomas has shown that some of them have monosomy 22 alone while others have additional abnormalities. Antioncogenes probably play a part in these tumors. Their identification will explain the neuro-oncogenesis process and perhaps open a new route for the treatment of brain tumors. PMID- 1919679 TI - Topographical study of supratentorial brain tumors. AB - The topographic analysis of supratentorial brain tumors must answer the following questions: location of the tumor, its extension, its being infiltrative or well localized and especially the relationships with the main functional areas such as the speech areas, the sensori-motor area, and the visuel areas. Also the topographic analysis may help to approach the diagnosis of nature. The neuroradiological procedures include the CT, the angiography and especially the MRI in sagittal and coronal sections, with gadolinium enhancement. The anatomical accuracy is obtained using the bicommissural plane and superimposition techniques according to the Talairach's Atlas and anatomical sections and MRI superimposition with angiography. 3D volumic reconstruction is of considerable contribution for the topographic analysis of a cerebral tumor. PMID- 1919680 TI - Astrocytic tumours. AB - Astrocytic tumours are frequent, accounting for nearly 50% of all brain tumours. They are divided into three groups: benign astrocytomas, anaplastic astrocytomas and malignant glioblastomas. The usual clinical manifestations of benign astrocytic tumours are epileptic seizures, whereas those of glioblastomas are rapidly progressing neurological deficits. These lesions show fairly characteristic neuroradiological features which have been largely studied. Injections of iodine-based or paramagnetic contrast media are important since they help in tumour grading: low-grade tumours are not enhanced, while glioblastomas are almost invariably enhanced. MRI seems to be indispensable for the study of astrocytic tumours: it provides an excellent anatomical analysis of the lesion during preoperative or pretherapeutic evaluation, and it is the only available method to confirm low-grade lesions that have passed unnoticed or have merely been suspected at CT. To avoid missing these tumours, every adult presenting with recent onset epileptic seizures should be explored by MRI using T2-weighted spin-echo sequences. PMID- 1919681 TI - Oligodendrogliomas. AB - Oligodendrogliomas are tumours developed from oligodendrocytes. They may be pure or associated with astrocyte proliferation. They are usually benign, but their malignancy grade is varied. These tumours affect middle-aged adults and are characterized by their slow growth and their fairly suggestive neuroradiological features which are those of a large, calcified, poorly enhanced, peripheral frontal lesion. Computerized tomography and magnetic resonance imaging are suitable complementary methods to characterize the tumour and evaluate its extension. PMID- 1919682 TI - Brain metastases. AB - Brain metastases are frequent, accounting for 20% of all brain tumours. The most common primary tumours responsible for brain metastases are lung cancer in man and breast cancer in women. Most metastases are located at the grey matter-white matter junction, in junctional vascular territories and in the rolandic region. Although non-specific, MRI is the most sensitive neuroradiological method for the lesions, especially when accompanied by gadolinium injection. MRI must absolutely be performed before surgical treatment, as gadolinium might detect other metastatic lesions or show metastatic tumours so small that they were not visible at computerized tomography (CT). PMID- 1919683 TI - Primary and secondary lymphomas of the brain: an MRI study. AB - Three types of lymphoma of the central nervous system are known: primary non Hodgkin's malignant lymphoma (NHML), secondary NHML and neurological lesions of Hodgkin's disease. NHML's are rare tumours, often associated with immunodeficiency and presenting predominantly as neuropsychological disorders. In this study 8 patients were explored by CT and MRI, with pathological confirmation. None of our patients had AIDS. The most typical neuroradiological image of this type of tumour is that of a large and intensely contrast-enhanced tumoral mass which is often multifocal and periventricular with infiltration of the subarachnoidal spaces and leptomeninges. Mass effect and perifocal oedema are less pronounced than expected with tumours of that size. NHML's may totally regress under corticosteroid therapy. This tumour of obscure aetiology must be recognized as it is now increasingly frequent. PMID- 1919684 TI - Magnetic resonance imaging in gangliogliomas and gangliocytomas of the nervous system. AB - Gangliogliomas and gangliocytomas are rare and benign neuronal tumors which affect young subjects. This study concerns 3 cases of ganglioglioma and 3 cases of gangliocytoma explored by CT and MRI and confirmed by pathological examination. The most typical CT image was that of an often calcified contrast enhanced cystic tumor. At MRI, each tumor emitted a low-intensity signal on T1 weighted sequences and a high-intensity signal on T2-weighted sequences. Contrast enhancement after gadolinium injection was frequent. Neuroradiology is not specific, and these tumors are usually diagnosed at pathology. However, the diagnosis may be considered in young patients with a history of old, drug resistant partial epilepsy and having a contrast-enhanced, calcified cystic lesion in the temporal lobe or the cerebellum. PMID- 1919686 TI - About the training seminar on nervous system imaging. PMID- 1919685 TI - Supratentorial ependymomas. Neuroradiological study. AB - Ependymoma is a rare tumour developed from ependymal cells and belonging to the group of neuroglial tumours. It may be located in any part of the central nervous system, but shows a preference for the ventricular cavities. Neuroradiology is not specific. CT shows a frequently large, calcified and cystic lesion of varied density and strongly contrast-enhanced. The signal emitted at MRI is often heterogeneous. Treatment consists of surgery combined with radiotherapy. Prognosis is poor owing to the difficulty of surgical excision and to the possibility of CSF grafts. PMID- 1919687 TI - A review of 2,413 tumours operated over a 30-year period. AB - Studying 2,413 cases of supratentorial brain tumors operated on a 30 years period, the author emphasizes appealing signs, pitfalls, and tumoral relapses. Epilepsy is the most frequent initial sign preceding headache and focal signs. We discuss the frequency of the epilepsy, the age of the first seizure, the location and the histological nature of the epiletogenic tumor, and the type of the seizures. In the end, we study diagnosis pitfalls such as long-standing epilepsy, ictal presentation, pitfalls due to metastases and the difficult problem of tumoral relapses. PMID- 1919688 TI - Now is our time. The 1991 AANS presidential address. AB - The President of the American Association of Neurological Surgeons (AANS) in his presidential address discussed the challenges faced by neurosurgery today. He stressed three essentials to meeting the future: an effective and introspective organization; ample participation by the membership of the specialty; and a plan. He defined some of the problems before neurosurgery and the strategic planning process that has been undertaken during his presidency. PMID- 1919689 TI - Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia. AB - Although experimental and pathological studies suggest an important role for ischemia in the majority of fatal cases of traumatic brain injury, ischemia has been a rare finding in most clinical studies of cerebral blood flow (CBF) in head injured patients. The hypothesis of the present study was that cerebral ischemia occurs in the first few hours after injury, but that CBF measurements have not been performed early enough. Early measurements of CBF (by the 133Xe intravenous method) and arteriovenous oxygen difference (AVDO2) were obtained in 186 adult head-injured patients with a Glasgow Coma Scale score of 8 or less, and were correlated with neurological status and outcome. During the first 6 hours after injury, CBF was low (22.5 +/- 5.2 ml/100 gm/min) but increased significantly during the first 24 hours. The AVDO2 followed the opposite course; the decline of AVDO2 was most profound in patients with low motor scores, suggesting relative hyperemia after 24 hours. A significant correlation between motor score and CBF was found in the first 8 hours after injury (Spearman coefficient = 0.69, p less than 0.001), but as early as 12 hours postinjury this correlation was lost. A similar pattern was found for the relationship between CBF and outcome. Cerebral blood flow below the threshold for infarction (CBF less than or equal to 18 ml/100 gm/min) was found in one-third of the studies obtained within 6 hours, the incidence rapidly decreasing thereafter. A low CBF after 24 hours was not generally associated with a high AVDO2, and was probably a reflection of low oxidative metabolism rather than frank ischemia. In 24 patients, a CBF of 18 ml/100 gm/min or less was found at some point after injury; the mortality rate was significantly higher in this subgroup, and survivors did worse. In some cases, ischemia was successfully treated by reducing hyperventilation or inducing arterial hypertension. These results support the above hypothesis, and suggest that early ischemia after traumatic brain injury may be an important factor determining neurological outcome. Moreover, these data indicate that early hyperventilation or lowering of blood pressure to prevent brain edema may be harmful. PMID- 1919690 TI - Endovascular occlusion of intracranial vessels for curative treatment of unclippable aneurysms: report of 16 cases. AB - Among 121 intracerebral aneurysms presenting at one institution between 1984 and 1989, 16 were treated by endovascular means. All 16 lesions were intradural and intracranial, and had failed either surgical or endovascular attempts at selective exclusion with parent vessel preservation. The lesions included four giant middle cerebral artery (MCA) aneurysms, one giant anterior communicating artery aneurysm, six giant posterior cerebral artery aneurysms, one posterior inferior cerebellar artery aneurysm, one giant mid-basilar artery aneurysm, two giant fusiform basilar artery aneurysms, and one dissecting vertebral artery aneurysm. One of the 16 patients failed an MCA test occlusion and was approached surgically after attempted endovascular selective occlusion. Treatment involved pretreatment evaluation of cerebral blood flow followed by a preliminary parent vessel test occlusion under neuroleptic analgesia with vigilant neurological monitoring. If the test occlusion was tolerated, it was immediately followed by permanent occlusion of the parent vessel with either detachable or nondetachable balloon or coils. The follow-up period ranged from 1 to 8 years. Excellent outcomes were obtained in 12 cases with complete angiographic obliteration of the aneurysm and no new neurological deficits and/or improvement of the preembolization symptoms. Four patients died: two related to the procedure, one secondary to rupture of another untreated aneurysm, and the fourth from a postoperative MCA thrombosis after having failed endovascular test occlusion. The angiographic, clinical, and cerebral blood flow criteria for occlusion tolerance are discussed. PMID- 1919691 TI - An analysis of the natural history of cavernous angiomas. AB - The advent of magnetic resonance (MR) imaging has permitted the recognition of many angiographically occult vascular malformations before the development of complications and subsequent surgical removal. This study reviews all patients at one institution who had radiographically identifiable vascular malformations believed to represent cavernous angiomas in order to obtain information on the natural history of this particular lesion. All 8131 craniospinal MR images performed at our medical center from January 1, 1986, to November 30, 1989, were reviewed, and 32 patients were identified with 76 lesions meeting the MR imaging criteria for cavernous angioma. Medical histories, physical examination records, and other data from these patients were then reviewed to determine the frequency of complications. Their mean age at latest follow-up examination (or at surgical removal of the lesion) was 37.6 years (range 16 to 72 years). Sixteen patients (50%) had a history of seizures, seven (22%) had focal neurological deficits, and three (9%) had clinically significant hemorrhage attributable to the cavernous angioma; six patients (19%) were asymptomatic. The estimated risk of hemorrhage for this population is 0.25%/person-year of exposure; the estimated risk of seizure development is 1.51%/person-year. Eight patients underwent surgical procedures, resulting in improved seizure control and/or lessened neurological deficit. Although these lesions are often excised with relative ease and minimal morbidity, the potential risks and benefits of surgery must be weighed carefully before removal of these relatively benign malformations. PMID- 1919692 TI - Natural history of the cavernous angioma. AB - The incidence and natural history of the cavernous angioma have remained unclear in part because of the difficulty of diagnosing and following this lesion prior to surgical excision. The introduction of magnetic resonance (MR) imaging has improved the sensitivity and specificity of diagnosing and following this vascular malformation. Seventy-six lesions with an MR appearance typical of a presumed cavernous angioma were discovered in 66 patients among 14,035 consecutive MR images performed at the Cleveland Clinic between 1984 and 1989. Follow-up studies in 86% of the cases over a mean period of 26 months provided 143 lesion-years of clinical survey of this condition. The most frequent presenting features were seizure, focal neurological deficit, and headache. While most lesions exhibited evidence of occult bleeding on MR imaging, there was overt hemorrhage in seven of the 57 symptomatic patients and only one overt hemorrhage occurred during the follow-up interval. The annualized bleeding rate was 0.7%. Analysis of the hemorrhage group revealed a significantly greater risk of overt hemorrhage in females. Pathological confirmation of cavernous angioma was obtained in all 14 surgical cases. This information assists in rational therapeutic planning and prognosis in patients with MR images showing lesions suggestive of cavernous angioma. PMID- 1919693 TI - The natural history of intracranial venous angiomas. AB - Cerebral venous angiomas are congenital anomalies of the intracranial venous drainage. Many believe that they are associated with a high risk of hemorrhage and neurological dysfunction, but newer neurodiagnostic imaging techniques are showing not only that they are more common than previously known but also that many have no associated symptoms. In this retrospective study, the natural history of venous angiomas was examined in 100 patients (48 males and 52 females) with radiographically identifiable lesions treated over a 14-year period. Information on the natural history of the lesion was obtained from clinical records and follow-up data. Imaging studies included angiography, computerized tomography, and magnetic resonance imaging. Angioma locations were classified as frontal (42 cases), parietal (24 cases), occipital (4 cases), temporal (2 cases), basal or ventricular (11 cases), cerebellar (14 cases), or brain stem (3 cases); 47 lesions were on the left side. Headache as a presenting symptom was common (36 patients) and often led to other radiographic studies, but this appeared to be related to the vascular lesion in only four patients. Other possibly related complications were hemorrhage in one patient, seizures in five, and transient focal deficits in eight. Fifteen patients had no neurological signs or symptoms. The mean patient age at last contact was 45.3 years (range 3 to 94 years). All patients have been managed without surgery. It is concluded that significant complications secondary to venous angiomas are infrequent and that surgical resection of these lesions and of surrounding brain is rarely indicated. PMID- 1919694 TI - Stereotactic ventrolateralis thalamotomy for medically refractory tremor in post levodopa era Parkinson's disease patients. AB - Thirty-six patients with Parkinson's disease and medically refractory tremor underwent stereotactic ventrolateralis thalamotomy at the Mayo Clinic between 1984 and 1989. All patients had been or were being treated with carbidopa/levodopa but with unsatisfactory tremor control. Modern stereotactic techniques, including microelectrode recording, were used to treat 36 patients, of whom 31 (86%) had complete abolition of tremor and three patients (5%) had significant improvement. Tremor recurred in two patients within 3 months of surgery; however, the remaining patients suffered no recurrence of tremor during follow-up periods ranging from 14 to 68 months (mean 33 months). Persistent complications (arm dyspraxia, dysarthria, dysphasia, or abulia) were noted in five patients but were a source of disability in only two. It is concluded that thalamotomy in carefully selected patients is a beneficial operation for the control of medically refractory parkinsonian resting tremor. PMID- 1919695 TI - Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. AB - There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3-buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 +/- 2 mm Hg (mean +/- standard deviation): control group), hyperventilation (PaCO2 25 +/- 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 +/- 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1-3 and 4-5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 +/- 1.7, 5.6 +/- 1.7, and 5.9 +/- 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p less than 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4-5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4-5.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919697 TI - Stereotactic rostral mesencephalotomy in cancer pain and deafferentation pain. A series of 40 cases with follow-up results. AB - Stereotactic rostral mesencephalotomy was performed in two groups of patients to investigate the long-term results in regard to pain relief. A standardized technique of target localization with ventriculography was used. Group A consisted of 33 patients with otherwise intractable pain due to cancer. Group B consisted of seven patients with deafferentation pain. Long-term pain relief was good (57%) for Group A and nonexistent for Group B patients. It is concluded that stereotactic rostral mesencepthalotomy is a valuable means for treating nociceptive cancer pain in lateral syndromes, but is of no value in neuropathic pain. Anatomical correlates for the results obtained are discussed and a hypothesis on the plasticity of the neo- and paleospinal afferent systems is formulated. PMID- 1919696 TI - Long-term outcome of 89 low-grade brain-stem gliomas after interstitial radiation therapy. AB - Between 1974 and 1985, 89 patients suffering from histologically confirmed, nonresectable low-grade astrocytomas located in the brain stem were entered into a retrospective study. Iodine-125 (125I) was implanted in 29 patients and iridium 192 (192Ir) in 26 patients. Computerized tomography revealed that 78% of the tumors in these patients were located chiefly in the mesencephalic region, 70% were circumscribed, and 78% were contrast-enhanced. Thirty-four patients underwent biopsy without prior aggressive tumor-specific therapy such as chemotherapy or external beam irradiation. Among these, 70% of the tumors were located predominantly in the pons, 74% were diffuse, and 59% were hypodense or isodense after contrast enhancement. Long-term follow-up investigations indicated that life expectancy after interstitial radiation therapy with 125I implanted directly by catheter either permanently or temporarily showed a more favorable trend than that after treatment with 192Ir. Interstitial radiation therapy with 125I appears to be an effective treatment for slowly proliferating, differentiated, well-delineated, nonresectable brain-stem gliomas. This technique makes it possible to achieve radiosurgical tumor control and, when carefully applied, represents the least traumatic treatment. Reduction of the tumor mass brings about improvement of the clinical symptoms. Further investigations on the biological behavior of brain-stem gliomas and prospective randomized long-term follow-up studies are necessary to evaluate the different kinds of treatment available for these patients. PMID- 1919698 TI - Cerebral vasospasm evaluated by transcranial Doppler ultrasonography at different intracranial pressures. AB - The present study evaluates the interdependence of clinical stage, cerebral vasospasm, intracranial pressure (ICP), and transcranial Doppler ultrasonographic parameters. The mean flow velocity of blood in the middle cerebral artery and the index of cerebral circulatory resistance as a measure of the peripheral vascular flow resistance were determined in 76 patients with spontaneous subarachnoid hemorrhage. The ICP was measured using an epidural transducer in 41 patients. There was no case in which both high ICP and a high mean flow velocity were observed simultaneously. The investigations led to the following conclusions. 1) In patients with a resistance index of less than 0.5, changes in the mean flow velocity seem to reflect sufficiently the actual severity and time course of vasospasm. 2) During the time course of vasospasm, an increase in the resistance index above values of 0.6 with a simultaneously decreased mean flow velocity indicates a rise in ICP rather than a reduction in vasospasm. 3) With a pronounced increase in ICP, evaluation of the severity and time course of vasospasm by transcranial Doppler ultrasonography based solely upon the mean flow velocity can lead to false-negative results. PMID- 1919699 TI - Predicting recovery of facial nerve function following injury from a basilar skull fracture. AB - Twenty-five patients with posttraumatic facial nerve palsy were studied. Partial recovery of function had occurred in 95% of these patients by 18 months after injury. At 5 months posttrauma, there was some recovery in 92.5% of those with a partial lesion compared with 10% of those with a complete lesion. This difference attains statistical significance. Complete recovery of nerve function had occurred by 10.5 months in 53.5% of the patients; in 62% of patients with a partial lesion, complete recovery had occurred by 4 months compared with 0% in those with a complete lesion. This difference also attains statistical significance. There was no statistically significant difference in recovery of function between patients with an immediate as opposed to a delayed onset of facial nerve palsy. It was determined that the degree of palsy had a statistically significant influence on recovery of facial nerve function, whereas the time of onset did not. The data presented support a conservative approach to these injuries and it is recommended that the possibility of surgical treatment should be entertained in patients with complete facial palsy persisting for 12 to 18 months after injury. PMID- 1919700 TI - A comparison of computerized tomography-guided stereotactic and ultrasound-guided techniques for brain biopsy. AB - Forty-one patients with brain lesions underwent brain biopsy using either a computerized tomography (CT)-guided stereotactic approach or an ultrasound-guided technique. The cases were selected according to location and size of the mass lesion. Lesions 15 mm or less in diameter and those in the posterior fossa were biopsied by a CT-guided stereotactic technique (18 patients). Supratentorial lesions with a diameter larger than 15 mm were approached using ultrasound guidance (23 patients). These criteria for procedure selection provided a diagnostic yield of 94% for the CT-guided procedures and 91% for those guided by ultrasound. Safety for the two procedures was similar. The ultrasound procedure was more rapid, simpler, and less costly to perform. It is concluded that, with the protocol described, CT-guided stereotactic procedures could be reserved for cases in which absolute accuracy is mandatory. PMID- 1919701 TI - Restoration of cerebrovascular responsiveness to hyperventilation by the oxygen radical scavenger n-acetylcysteine following experimental traumatic brain injury. AB - Previous experiments have shown that, following experimental fluid-percussion brain injury, cyclo-oxygenase-dependent formation of oxygen radicals prevents arteriolar vasoconstriction in response to hyperventilation. The oxygen radical scavengers superoxide dismutase and catalase restore normal reactivity; however, they are not routinely available for clinical use. The present study tested whether n-acetylcysteine (Mucomyst), an agent currently available for acetaminophen toxicity, could be used as a radical scavenger to restore reactivity after brain injury. N-acetylcysteine (163 mg/kg) was given intraperitoneally prior to or 30 minutes after fluid-percussion brain injury (2.6 atm) in cats, and reactivity to hyperventilation was tested 1 hour after injury. The authors found either that pre- or postinjury administration led to normal reactivity. Additional experiments supported the hypothesis that n-acetylcysteine is an oxygen radical scavenger, since it reduced or prevented the free radical dependent cerebral arteriolar dilation normally induced by the topical application of arachidonic acid or bradykinin. The mechanism by which n acetylcysteine is effective in trauma may involve direct scavenging of radicals or stimulation of glutathione peroxidase activity. The results suggest that n acetylcysteine may be useful for treatment of oxygen free radical-mediated brain injury. PMID- 1919702 TI - Rapid growth of residual aneurysmal neck during pregnancy. Case report. AB - The pregnant state has an apparently stimulatory effect on the tendency for aneurysms to grow. A patient is reported whose symptomatic aneurysm was clipped during pregnancy. The small amount of residual aneurysm underwent remarkable continued growth during the last trimester of the pregnancy. The implications for management of such cases are discussed. PMID- 1919703 TI - Trigeminal neuralgia caused by compression from arteries transfixing the nerve. Report of three cases. AB - The authors present three patients with trigeminal neuralgia due to compression by an artery that transfixed the sensory root of the fifth cranial nerve. These cases represented 0.8% of 384 patients with trigeminal neuralgia treated by microvascular decompression at the authors' clinic during the past 12 years. In the remaining 381 cases, the compressing vessels were successfully removed from the trigeminal nerve without much difficulty, for an initial cure rate of 94.3%. In the three cases reported, however, the compressing artery penetrating the nerve could not easily be maneuvered away from the nerve. In the first two cases, partial rhizotomy perpendicular to the axis of the nerve at the site of arterial transfixion made it possible to separate the artery from the nerve. However, these two patients developed postoperative facial sensory impairment. In the third case, rhizotomy was performed longitudinal to the axis of the nerve at the site of arterial transfixion, making it possible to reposition the artery peripherally beyond the root entry zone of the nerve without causing any postoperative sensory deficits of the face. No recurrent pain has developed in more than 2 1/2 years since surgery in any of these three cases. When performing microvascular decompression surgery on patients in whom the compressing artery penetrates the nerve, the technique used in our third patient is the procedure of choice. PMID- 1919704 TI - Elevated intracranial pressure from cerebral venous obstruction by Masson's vegetant intravascular hemangioendothelioma. Case report. AB - The case is described of a 15-year-old girl with papilledema and visual obscurations caused by a rare lesion, Masson's vegetant intravascular hemangioendothelioma, within the venous sinus at the torcular herophili. This lesion impeded cranial venous outflow, leading to intracranial hypertension. PMID- 1919705 TI - Chiari malformation with syringocephaly. Case report. AB - A 69-year-old white woman presented with a left hemiparesis which progressed to quadriparesis and encephalopathy. Computerized tomography and magnetic resonance imaging revealed a Chiari I malformation and a hydromyelic cavity extending from C-2 to T-6. Rostrally, the cavity extended through the ventral medulla, pons, and right cerebral peduncle into the right cerebral hemisphere, where the cavity enlarged and was associated with mass effect. The patient has made a dramatic neurological recovery following suboccipital craniectomy with insertion of a dural graft to decompress the Chiari malformation and upper cervical laminectomy and dorsal root entry zone myelotomy to decompress the hydromyelia. PMID- 1919706 TI - Neuromuscular hamartoma (benign "triton" tumor) of the brachial plexus. Case report. AB - Neuromuscular hamartoma (choristoma) or benign "triton" tumor is a very rare peripheral-nerve tumor composed of mature nerve fibers and well-differentiated striated muscle fibers. Only seven cases have been reported in the literature. A new case of this rare entity is described in a 36-year-old white woman with a recurrent left supraclavicular mass in the brachial plexus area. Unlike the previous cases, this patient had continued to have proliferation of her tumor since childhood, requiring total resection in adulthood. It is concluded that total resection of these tumors should be attempted at initial diagnosis. The histogenesis of these tumors remains unclear. They may represent proliferation of neuroectodermal-derived or limb mesodermal tissue in the elements of a peripheral nerve. PMID- 1919707 TI - Compulsive polydipsia following meningioma resection: an epileptic phenomenon? Case report. AB - The authors report the case of an individual who developed compulsive polydipsia following resection of a left sphenoidal ridge meningioma. The episodic, stereotyped nature of his symptoms, response to treatment, and electroencephalographic and magnetic resonance imaging findings are all highly consistent with temporal lobe-onset epilepsy. The pathophysiology of this underrecognized phenomenon is discussed. PMID- 1919708 TI - Monostotic fibrous dysplasia of the clivus. Case report. AB - A case report of monostotic fibrous dysplasia of the clivus in a postadolescent woman is described. Although fibrous dysplasia of craniofacial structures is well documented, involvement of the clivus has not been reported. Diagnosis by clinical, radiographic, and histopathological features is detailed. Implications for the role of surgery and management are discussed. PMID- 1919709 TI - Dorsal selective rhizotomy through a limited exposure of the cauda equina at L-1. Technical note. AB - The technique of the dorsal selective rhizotomy as originally developed by Professor Fasano and by the author is described. The rhizotomy is performed through a one-level laminectomy at L-1. Exposure of the conus medullaris and the cauda equina at this level is adequate to thoroughly assess the reflex electrical response to stimulation of the lumbosacral roots and to section the selected roots/rootlets. This approach, based on over 100 surgical procedures, obviates the need for an extensive laminectomy in a growing child without compromising the clinical results. PMID- 1919710 TI - The image of the "brain surgeon" in American culture: the influence of Harvey Cushing. AB - In contemporary American culture, the term "brain surgeon" conjures up the image of an intensely single-minded professional, who deals with terribly complex matters of life and death. These descriptors find their personification in Harvey Cushing, because they are derived directly from him. This hypothesis was tested by a complete search of the New York Times Index and the Reader's Guide to Periodical Literature for the years 1919 to 1942. All entries for Harvey Cushing were reviewed in the original sources. In the New York Times, Cushing's first significant exposure was in response to his winning a Pulitzer Prize in 1925. Major editorial coverage began in 1934, and was especially prominent with the publication of From a Surgeon's Journal in 1936. The process of lionizing Cushing by creating an overdrawn caricature reached its apotheosis in Time magazine in 1939. The Time article was actually a report of Cushing's 70th birthday party. It expounded all of the descriptors that are now associated with "brain surgeon". Thus, it was Cushing's literary skills that initially brought him recognition from editors who were arbiters of public opinion. This attention seems to have been the conduit to his mythologization by the larger public. Although unnamed, it is really Cushing's image that still persists as the prototypical "brain surgeon" in the collective American consciousness. PMID- 1919712 TI - The Montreal Neurological Institute. AB - In this centenary year of Wilder Penfield, his contribution to the creation of the Montreal Neurological Institute is reviewed. In the early 1930's, a confluence of favorable circumstances at McGill University and the Royal Victoria Hospital, Montreal, made it possible for Wilder Penfield, with his partner William Cone, to realize his dream of a combined neurological hospital and research institute. Endowed by the Rockefeller Foundation and with initial and ongoing support from community and governments, the Montreal Neurological Institute has continued its exponential growth over the past half-century as a world center for the study and treatment of disorders of the brain and nerves. PMID- 1919711 TI - Origins of Wilder Penfield's surgical technique. The role of the "Cushing ritual" and influences from the European experience. AB - Wilder Penfield left two great legacies: the development of successful surgical treatment of epilepsy and the establishment with his colleagues of the Montreal Neurological Institute as a world-renowned medical center, "dedicated to relief of pain and suffering and to the study of neurology." That Harvey Cushing's surgical ritual (which stemmed from the painstaking operative methods of Halsted) played a paramount role in the origins of Penfield's surgical technique is revealed by a set of notes and drawings by Penfield during repeated visits in the 1920's to Cushing's clinic at the Peter Bent Brigham Hospital. Penfield's intellectual approach to the nervous system was derived from his studies with Sherrington. Holmes, Cajal, and Hortega. His eclectic surgical style emerged from his familiarity with the operating techniques of Halsted, Dandy, Horsely, Sargent, Cushing, Frazier, Whipple, Leriche, and Foerster. Penfield's debt to these teachers is documented in his memoirs and in an unpublished report on European neurosurgery which he sent ot the Rockefeller Foundation in 1928. PMID- 1919713 TI - Chiari's description of cerebellar ectopy (1891). With a summary of Cleland's and Arnold's contributions and some early observations on neural-tube defects. AB - One hundred years ago, Chiari published his first paper on cerebellar ectopy. The contribution of his paper and those of Cleland (1883) and Arnold (1894) to the development of the knowledge of craniocervical abnormalities is discussed. Some early contributions (those of Tulp and Ollivier d'Angers) to the subject of neural-tube defects were also studied and it is concluded that Chiari's name should be connected with the different types of cerebellar ectopy. PMID- 1919714 TI - Temporal lobectomy and language function. PMID- 1919715 TI - Morbidity associated with subdural electrodes. PMID- 1919716 TI - Thalamotomy lesions. PMID- 1919717 TI - Intramedullary schwannoma. PMID- 1919718 TI - Thecoperitoneal shunting for syringomyelia. PMID- 1919719 TI - Halifax clamps for posterior cervical fusion. PMID- 1919720 TI - Hypertrophy of epidural fat vs. encapsulated lipomas. PMID- 1919721 TI - Practical matters with Henry N. Wagner, Jr., MD. PMID- 1919722 TI - Detection of subacute infectious foci with indium-111-labeled autologous leukocytes and indium-111-labeled human nonspecific immunoglobulin G: a prospective comparative study. AB - In 35 patients suspected of an infectious focus, the outcome of scintigraphy with 111In-labeled autologous leukocytes (WBC) and 111In-labeled human nonspecific immunoglobulin G (IgG) was evaluated in a prospective comparative study. Clinical, roentgenologic and microbiologic findings were considered to be proof of the presence of infection or inflammation. In this group of patients with mainly subacute infections, 111In-IgG scintigraphy performed significantly better than 111In-WBC scintigraphy, especially in infections of the locomotor system, but also in various soft-tissue infections. Both techniques showed disappointing results in patients with disseminated yersinia infection and in some patients with tuberculosis. Overall sensitivity and specificity was 74% and 100% for 111In IgG scintigraphy and 52% and 78% for 111In-WBC scintigraphy, respectively. PMID- 1919723 TI - Radionuclide diagnosis of vertebral osteomyelitis: indium-111-leukocyte and technetium-99m-methylene diphosphonate bone scintigraphy. AB - Seventy-six 111In-labeled leukocyte images performed on 71 patients with possible vertebral osteomyelitis were reviewed. Twenty-eight cases of vertebral osteomyelitis were diagnosed. Vertebral labeled leukocyte activity was normal in 2, increased in 11, and decreased in 15 cases of osteomyelitis. The median duration of symptoms was significantly longer in patients with osteomyelitis and decreased vertebral activity than in patients with osteomyelitis and increased activity (3 mo versus 2 wk; p = 0.019). No significant relationship between the duration of antibiotic therapy and the appearance of vertebral osteomyelitis on leukocyte images was identified (p = 0.62). Increased vertebral activity was highly specific (98%) for osteomyelitis but relatively insensitive (39%). Decreased activity was neither sensitive (54%) nor specific (52%). Seven patients with clinically resolved infection underwent follow-up imaging. Of four patients who initially presented with increased activity, one had normal and three had decreased vertebral activity on follow up studies. All three patients with decreased activity initially had decreased activity on follow-up. Using increased or decreased activity as criteria for infection, the accuracy of leukocyte imaging for diagnosing vertebral osteomyelitis was 66%, similar to that of 99mTc bone imaging (63%) in our population. Leukocyte imaging did however provide important information about extraosseous infection in 12 of the patients studied. PMID- 1919724 TI - Effects of visual stimulation on the redistribution of iodine-123-IMP in the brain using SPECT imaging. AB - A study was performed to validate the assumption that redistribution and clearance of [123I]IMP localization in the brain are unaffected by changes in ambient light levels and visual stimulation occurring after radiopharmaceutical is administered and deposited in the brain. Serial SPECT and planar imaging studies were performed on six healthy, volunteer, adult male subjects under resting, nonactivation conditions. Studies were repeated 7 days later with each subject exposed to strobe light stimulation prior to delayed SPECT procedures at 3 hr. Redistribution and clearance of 123I-IMP in the brain were examined in cortical, subcortical, and cerebellar regions on transaxial slices for the two sets of serial procedures in each subject. Visual stimulation following the initial uptake of [123I]IMP did not affect the distribution or clearance of [123I]IMP in the brain, including the visual cortex, and therefore should not influence the interpretation of delayed SPECT images. PMID- 1919725 TI - Clinical significance of the solitary functioning adrenal gland. AB - To assess the compensatory functional and anatomic changes in the remaining adrenal cortex after unilateral adrenalectomy or in the unaffected adrenal in patients with unilateral adrenal destruction by neoplasm, 17 patients with a single, functioning adrenal gland and normal indices of adrenocortical function, nine after adrenalectomy and eight with a unilateral, destructive adrenal lesion were studied with 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy and computed tomography. Adrenal masses with a mean (+/- s.d.) diameter of 2.8 +/ 1.0 cm; (range 1-4 cm; 95% confidence interval (Cl), 2.5-3.1 cm) were identified by computed tomography in seven of nine patients in the remaining adrenal cortex at variable times (6.1 +/- 5.9 y; range 0.5-19 y) after unilateral adrenalectomy. Mean (+/- s.e.m.) NP-59 uptake was elevated (p less than 0.01) in both adrenalectomy and adrenal destruction groups, mean uptake (+/- s.e.m.) was 0.32% +/- 0.04% administered dose (95% Cl, 0.24%-0.4% administered dose) as compared to normal (0.16% +/- 0.05% administered dose, 95% Cl, 0.06%-0.26% administered dose). The remaining adrenal cortex may be anatomically abnormal after unilateral adrenalectomy and demonstrate compensatory, increased NP-59 uptake in the presence of overall, normal adrenocortical function. PMID- 1919726 TI - Hepatopulmonary steal in PCP. PMID- 1919727 TI - 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA): evaluation in mouse of a new probe of myocardial utilization of long chain fatty acids. AB - 14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid (FTHA) is a new radiolabeled long chain fatty acid (LCFA) analog designed to undergo metabolic trapping subsequent to its commitment to the beta-oxidation pathway. Sulfur-substitution at the sixth carbon of FTHA causes a prolonging of myocardial clearance half-time (T 1/2 approximately 2 hr) in mice with little diminution of myocardial uptake (39.8 +/- 3.0% ID/g at 5 min). Heart-to-blood ratios were 20 +/- 6 and 82 +/- 16 at 1 and 60 min, respectively. In contrast, the 3-thia analog, 13(R,S)-[18F]-fluoro-3-thia hexadecanoic acid, showed lower uptake and poor retention by heart. Myocardial uptake of FTHA was reduced by 81% (p less than 10(-5) and 87% (p less than 5 x 10(-4] in mice pretreated with the carnitine palmitoyltransferase I inhibitor, 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) at 1 and 60 min, respectively. Radioanalytical studies showed the major metabolic fate of FTHA in control and POCA treated myocardium to be unidentified metabolite(s) that bind to tissue protein. Smaller amounts of 18F radioactivity were present in myocardium as complex lipids, fatty acid, and unidentified soluble metabolites. The results indicate metabolic trapping of FTHA in myocardium subsequent to its entry into the mitochondrion and encourage its further evaluation as a PET tracer of myocardial LCFA utilization. PMID- 1919728 TI - HMPAO-SPECT and MRI in acute disseminated encephalomyelitis. PMID- 1919729 TI - Normalization of stress and delayed thallium-201 myocardial SPECT: where is the normal reference area? AB - We describe an unusual uptake pattern in a thallium SPECT study performed after dipyridamole infusion in a patient with a documented history of prior inferior infarction and recent typical chest pain. The stress study exhibited maximum uptake in the inferior wall. The delayed study showed an inferior defect more consistent with the notion of inferior necrosis, with a maximum uptake in the anterior wall. The authors propose a pathophysiologic interpretation consistent with coronary angiography findings, based on the assumption of coronary steal suggested by the occurrence of chest pain at the end of the dipyridamole infusion. The problem of selecting myocardial normal reference area(s) necessary to normalization prior to quantitative comparison stress and delayed studies is discussed. PMID- 1919730 TI - Pachydermoperiostosis: technetium-99m-methylene diphosphonate scintigraphic pattern. AB - We present two cases of pachydermoperiostosis. Both patients presented with joint pains and swelling. Bone scan revealed marked pericortical uptake involving the distal end of long bones. The distribution pattern and differential diagnosis of the scan abnormalities are discussed. PMID- 1919731 TI - Skeletal angiomatosis limited to the hand: radiographic and scintigraphic correlation. AB - Three-phase bone scintigraphy elegantly demonstrates the vascular nature of the expansile, lytic lesions of skeletal angiomatosis and the induced bony changes in the involved areas. Unusual features of the case include its confinement to the hand and rapid progression as shown by serial radiographs. PMID- 1919732 TI - Bilateral subdural hematomas diagnosed with technetium-99m-HMPAO brain SPECT. AB - An elderly patient with a complex history of organic dementia but a normal neurologic examination had a 99mTc-hexamethylpropylene-amine-oxime (HMPAO) brain scan for a suspected cerebrovascular accident or space-occupying lesion. The study showed no perfusion abnormality in the brain parenchyma, but bilateral flattening and inversion of the normal hemispheric convexities, with separation from the skull was identified. Bilateral subdural hematomas (SDH) were suspected and the patient had a computed tomographic scan that confirmed the diagnosis. PMID- 1919733 TI - Comparison of bicycle and treadmill radionuclide angiocardiography. AB - The purpose of this study was to test motion-correction algorithms for initial transit radionuclide angiocardiograms acquired at rest and during bicycle and treadmill exercise. Treadmill data was spatially reoriented by computer software designed to eliminate motion of a 125I point source simultaneously recorded at a lower energy window. A second algorithm based on left ventricular centroid counts further corrected for motion on all studies. Exercise left ventricular ejection fraction was higher on the treadmill (0.68 +/- 0.07) compared to the bicycle (0.64 +/- 0.08) (p less than 0.0001, r = 0.88). Treadmill exercise also resulted in larger end-diastolic volumes (180 +/- 30 versus 157 +/- 36, p less than 0.0001), stroke volumes (124 +/- 28 versus 101 +/- 29, p less than 0.0001) and cardiac outputs (19.9 +/- 4.6 versus 15.9 +/- 5.0, p less than 0.0001). Similar variances for these hemodynamic measurements suggest that the mean differences observed were physiologic and that error from body motion was effectively corrected by this approach. We conclude that the measurement of left ventricular function during treadmill exercise, when combined with these techniques for correcting motion, is a reasonable alternative to conventional bicycle exercise. PMID- 1919734 TI - Three-dimensional SPECT simulations of a complex three-dimensional mathematical brain model and measurements of the three-dimensional physical brain phantom. AB - We have developed a three-dimensional computer simulation of SPECT imaging. We have applied the simulation procedure to the realistic mathematical Hoffman three dimensional brain model to generate the projection data (in the absence of attenuation, scatter, or noise) of both a parallel-hole and a multidetector SPECT system with point-focusing collimators. The simulated projection data were then reconstructed using standard software. The projection data resulting from the distribution of grey matter alone, or grey and white matter, were simulated. The results of these simulations indicate the existence of significant qualitative and quantitative artifacts in reconstructed human brain images. For example, the reconstructed values for grey matter along a cortical circumferential profile in a transverse slice through the basal ganglia varied by a factor of 2.40 (parallel hole) and 2.99 (point-focusing), although the original grey matter values were identical in all cortical regions in the model. We have compared the simulated reconstructed images with those obtained by imaging the physical three dimensional Hoffman brain phantom, which was constructed based upon the same set of data from which the mathematical three-dimensional Hoffman brain model was derived. Although the simulation did not include all of the degrading factors present in the physical imaging, the two images were in good agreement, indicating the applicability of the simulation to a realistic situation and the importance of the detector resolution effect. PMID- 1919735 TI - Optimal scan time of oxygen-15-labeled water injection method for measurement of cerebral blood flow. AB - We investigated the optimal scan time for obtaining the maximal signal-to-noise (S/N) ratio in cerebral blood flow (CBF) measured by PET imaging following 15O water bolus injection. We performed sequential measurements with dynamic scans of six subjects injected at rest while listening to white noise. Each dynamic data set was edited into images corresponding to different scan times and were calibrated to CBF images by the table look-up method. For each scan time, we evaluated a pixel-by-pixel standard deviation of the CBF for sequential measurements. The S/N-ratio of CBF in the gray matter was 10.2 +/- 1.7 and 13.6 +/- 2.9 at a 40 and 120 sec scan time, respectively. The gain of the 120-sec over 40-sec scan time corresponds to an 80% increase in the number of trials to reach the same S/N-ratio in a stimulation-activation study. The simulation study supported the results, in which the maximal S/N-ratio of the CBF was demonstrated to be 90 and 120 sec at a CBF of 80 and 60 ml/100 ml/min, respectively. It is concluded that the optimal scan time of the 15O-water bolus injection method is in the interval from 90 to 120 sec. PMID- 1919736 TI - Optimization of regional cerebral blood flow measurements with PET. PMID- 1919737 TI - Measurements of regional ventilation pulmonary gas volume: theory and error analysis with special reference to positron emission tomography. AB - The adaptation to PET of the steady-state technique for the measurement of alveolar ventilation, based on the short-lived radionuclide 19Ne (T1/2 = 17.4 sec), allows the steady-state lung model to be analyzed in a quantitative way under well-defined geometrical conditions. The regional gas volume is essential to this analysis, and regional measurements of the pulmonary gas volume based on transmission tomography are presented and validated in this paper. The accuracy of the steady-state method rests largely with the validity of the lung model applied to describe the transport of tracer in the lung. This study considers tracer transport and mixing within individual lung regions. Blood flow and the alveolar-to-capillary exchange of gases do not significantly affect the values obtained, not even in regions with highly abnormal ventilation/perfusion ratios. A nonuniform intra-regional gas flow distribution results in an underestimation of the regional ventilation, determined by the dispersion of the ventilatory turnover rates of alveolar gas within the region. In the normal lung this underestimation is negligible. In disease, a mixing within the resolution volume of units that are almost non-ventilated and units that perform normally may result in an underestimation of alveolar ventilation by up to 60%. PMID- 1919738 TI - Effect of carbon-11-acetate recirculation on estimates of myocardial oxygen consumption by PET. AB - Mono- and biexponential fitting of myocardial 11C-acetate kinetics does not account for the effect of recirculating 11C activity following intravenous injection of the tracer. A tracer kinetic model comprising two and three compartments was developed to describe intravascular and myocardial 11C-acetate kinetics defined by PET. This model approach including a correction for 11C metabolites in blood was validated by correlating the model parameter estimates with directly measured oxygen consumption (MVO2) in 11 closed-chest dog experiments over a wide range of cardiac work. The model parameter k2 closely correlated with oxygen consumption (r = 0.94). This approach was subsequently applied to human studies and k2-related to rate-pressure product (PRP). In comparison to conventional monoexponential fitting of 11C-acetate tissue kinetics, the model approach improved the correlation coefficients of scintigraphic MVO2 estimates and PRP values from 0.61 to 0.91. Thus, analysis of myocardial 11C-acetate and clearance kinetics with a tracer kinetic model corrects for recirculating 11C-activity and may provide more consistent estimates of myocardial oxygen consumption. PMID- 1919739 TI - Relationship between myocardial clearance rates of carbon-11-acetate-derived radiolabel and oxidative metabolism: physiologic basis and clinical significance. PMID- 1919740 TI - Tomographic myocardial perfusion imaging with technetium-99m-teboroxime at rest and after dipyridamole. AB - This study was done to determine whether the rapidly clearing myocardial perfusion agent 99mTc-teboroxime (SQ 30217, Cardiotec) could be combined with tomographic imaging to accurately quantify regional myocardial blood flow distribution in anesthetized dogs. Following stenosis of the anterior descending (LAD, n = 10) or circumflex (LCX, n = 5) coronary arteries, teboroxime was administered simultaneously with radioactive microspheres, at rest and following infusion of dipyridamole (0.15 mg/kg/min x 4 min). Tomographic imaging began 1 min after each teboroxime injection and continued for 12 min. For LAD stenosis, when the dipyridamole study was performed first, teboroxime activity in the center of the ischemic region was closely correlated with tissue microsphere content. However, the severity of the dipyridamole-induced flow deficit was underestimated by teboroxime when the rest study was performed first. Our results show that despite rapid myocardial clearance, tomographic imaging of 99mTc teboroxime provides reasonably accurate quantitation of dipyridamole-induced anterior wall perfusion defects, but that the flow deficit is underestimated when a rest study is performed first or when the defect is located in the inferior wall. PMID- 1919741 TI - Increased accumulation of hexakis (2-methoxyisobutylisonitrile)technetium(I) in osteosarcoma and its metastatic lymph nodes. AB - Scintigraphy using hexakis (2-methoxyisobutylisonitrile) technetium (I) [Tc-MIBI] was performed in a patient with osteosarcoma of the right tibia. Increased accumulation of Tc-MIBI was observed in the primary site of the tumor as well as in metastatic lesion of the right inguinal lymph nodes, which were later confirmed by biopsy. PMID- 1919742 TI - The effect of flow on technetium-99m-teboroxime (SQ30217) and thallium-201 extraction and retention in rabbit heart. AB - In order to evaluate the accuracy of blood flow measurement, the single-pass extraction, retention/wash-out and relative net uptake of 99mTc-teboroxime (SQ30217) and 201Tl were evaluated and compared in 20 isolated blood-perfused rabbit hearts at coronary flow rates ranging from 0.49 to 2.85 ml/g wet wt min-1. The average peak extraction of 201Tl (+/- s.d.) (0.67 +/- 0.11) marginally exceeded that of SQ30217 (0.62 +/- 0.12) (p = 0.06). Flow significantly affected the maximum net extraction of 201Tl and the 40-min net extractions of both 201Tl and SQ30217. Unexpectedly, the rate of 201Tl myocardial washout was significantly faster (p less than 0.05) than SQ30217 washout at all flow rates evaluated. Increasing coronary blood flow rate was associated with a more rapid clearance of both tracers from the myocardium (p less than 0.05 for both comparisons). The slope of the linear correlations between relative net SQ30217 uptake versus flow and relative net 201Tl uptake versus flow were found to be similar for up to 10 min after isotope injection. These data were interpreted to indicate that: 1. Thallium-201 might be slightly better extracted than SQ30217. 2. SQ30217 is cleared more slowly from the myocardium. 3. Thallium-201 and SQ30217 appear to be comparable tracers of myocardial perfusion for up to 10 min after injection under the single-pass conditions currently employed. 4. Additional studies are needed to clarify myocardial SQ30217 kinetics. PMID- 1919743 TI - Is there additional useful information in the myocardial washout characteristics of teboroxime? PMID- 1919744 TI - Enhancement by tetraphenylborate of technetium-99m-MIBI uptake kinetics and accumulation in cultured chick myocardial cells. AB - Myocellular uptake and retention of technetium-99m-hexakis (2 methoxyisobutylisonitrile) (Tc-MIBI), a lipophilic cationic myocardial perfusion and viability imaging agent, is dependent on both mitochondrial and plasma membrane potentials. To test for enhancement of uptake kinetics by lipophilic anions, cultured chick heart cells were exposed to tetraphenylborate (TPB), which produced a concentration-dependent maximal 15-fold increase in Tc-MIBI uptake kinetics (at 3 x 10(-5) M) and enhanced peak accumulation of Tc-MIBI from 165.4 +/- 26.3 to 705.6 +/- 61.3 fmoles/mg protein.nMo (P less than 0.001). Carbonyl cyanide-m-chloro phenylhydrazone (CCCP; 10(-5) M), a mitochondrial uncoupler, rapidly depleted cellular content of Tc-MIBI in the presence of TPB (10(-5) M) from 300.0 +/- 30.0 to 42.5 +/- 1.9 fmole/mg protein.nMo (p less than 0.001). TPB enhanced both uptake rates and net accumulation of Tc-MIBI at all buffer Ko concentrations between 130 mM and 0.54 mM. Tc-MIBI influx rates allowed estimation of plasma-membrane potential as a function of Ko in the presence of valinomycin with a slope of -67 mV/decade (r = -0.99). The results further support a potential-dependent mechanism for cell uptake of Tc-MIBI and suggest a rational approach for increasing tissue extraction fraction in vivo. PMID- 1919746 TI - Differential myocardial washout of technetium-99m-teboroxime: mechanism and significance. PMID- 1919745 TI - Demonstration of differential post-stenotic myocardial technetium-99m-teboroxime clearance kinetics after experimental ischemia and hyperemic stress. AB - The clearance kinetics of the perfusion tracer 99mTc-teboroxime were evaluated in post-stenotic and normal myocardium using dynamic planar gamma camera imaging in pre-instrumented dogs in the control state (n = 9) and following total occlusion (2 min), pharmacologic stress with adenosine [80 and 160 micrograms/kg/min] or dipyridamole, and rapid atrial pacing (220/min). Technetium-99m-teboroxime clearance in normal myocardium was accelerated by adenosine and by dipyridamole compared to the control state (8.9 +/- 1.1 and 9.3 +/- 1.9 min versus 11.9 +/- 1.8 min; p less than 0.05). Post-stenotic 99mTc-teboroxime clearance half-time was most significantly prolonged compared to nonoccluded contralateral perfusion zones by 160 micrograms/kg/min adenosine stress (11.2 +/- 3.7 versus 6.3 +/- 1.5 min) and by complete coronary occlusion (12.1 +/- 3.3 versus 6.6 +/- 1.2 min; both p less than 0.05). Differential tracer clearance from post-stenotic versus nonoccluded zones produced quantitative evidence of relative defect "redistribution" in 71% of maximal stress studies at a mean of 8.8 +/- 2.5 min postinjection. Sensitivity, specificity, and diagnostic accuracy of prolonged regional 99mTc-teboroxime clearance rates for post-stenotic perfusion abnormalities were 62%, 100% and 81% in maximal stress studies. Future clinical trials of exercise and nonexercise stress 99mTc-teboroxime imaging should consider these kinetic characteristics and examine the correlates of perfusion defect "redistribution." PMID- 1919747 TI - The packaging of intravenous Persantine. PMID- 1919748 TI - Determining gastric emptying rate. PMID- 1919749 TI - A novel in vivo red cell-specific label. PMID- 1919750 TI - Gallium uptake in eosinophilia myalgia syndrome. PMID- 1919751 TI - Proposal of a modified scintigraphic method to evaluate duodenogastroesophageal reflux. PMID- 1919752 TI - Detection of reversible thallium-201 defects with ribose. PMID- 1919753 TI - Preparing documentation for a JCAHO visit. AB - This article describes a documentation format for Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) standard 6. A system for maintaining ongoing documentation is presented. Once in place, only a few "last minute" items need preparation prior to a JCAHO visit. In the weeks preceding the visit, department members can review the materials for accuracy and completeness and ensure that the document adequately reflects the extent and quality of the department's activities. The system is easily adapted to changes in JCAHO standards. PMID- 1919754 TI - Energizing professional orientation. AB - With many hospitals replacing the equivalent of their entire nursing staff every 5 years, a comprehensive orientation program is a critical strategic activity for nursing departments. Using the socialization process of new employees as a framework, orientation in health care can be restructured and energized. This article discusses current business practices designed to facilitate the entry process of new employees. Model orientation programs in business and nursing are described to assist staff development educators. PMID- 1919755 TI - Filipino GN to Filipino RN. A well-developed plan leads to success. AB - This article describes the authors' experience in designing a hospital orientation program for newly recruited Filipino nurses. The nursing department's educational and administrative efforts helped to orient the newly recruited nurses to the hospital and to nursing practice in the United States and prepared them to pass the NCLEX examination. Specific classes included in the orientation are presented. Topic title, time frame, facilitator, components, and rationale for each class are discussed. Suggestions for timing of recruitment and clinical orientation assignments are given. Staff preparation to Philippine culture and nursing practice is also reviewed. The authors believe this information would assist other nursing departments prepare for recruited Filipino nurses on their staff. PMID- 1919756 TI - Promoting nursing quality through supervision. AB - This article discusses the concept and content of supervision and related forms of staff training. Of special concern is the implementation of supervision in nursing organizations and its role in promoting nursing quality. Finally, the article looks at the future prospects of supervision and the need for further development. In Finland, supervision was first introduced as a method of staff training in the 1960s, but it is only during the past decade or so that it has been adopted on a wider scale in different fields of health care. Recently, there has been increasing debate on the definition of the concept, on its content, and on how supervision should be distinguished from other forms of staff training. Critics are saying that existing conceptual analyses are superficial and remain surrounded by considerable ambiguity. In the practice of nursing supervision, the emphasis is often too heavily on the problems of nursing practice. As a result, any creative new ideas on the part of the supervised employee are easily ignored. Every effort should now be made to develop a more accurate and comprehensive definition of supervision by closely comparing supervision with related forms of staff training, many of which differ from supervision only marginally in terms of, say, goals and contents. Supervision is here compared with consultation, hierarchic supervision, guidance, and therapy. PMID- 1919757 TI - Evaluating the affective domain. Consider a Likert scale. AB - An affective component of learning exists in every educational program developed, yet evaluating this aspect remains a challenge for nurse educators. An attitudinal scale should be considered one means of discovering nurses' attitudes and beliefs relative to a particular learning experience. Practical guidelines for developing and improving Likert scales, as well as interpreting scores, are the focus of this article. PMID- 1919758 TI - Nursing process, nursing diagnoses, and care plans in a clinical setting. AB - Staff development educators assist professional nursing staff in providing personalized, quality patient care that is documented in an accurate, time-saving manner with periodic evaluation of outcomes. They also seek ways to assist administrators in improving quality assurance in health care facilities. This article describes nursing care plans based on North American Nursing Diagnosis Association (NANDA) taxonomy that can meet recognized standards of patient care and be adapted for acute or long-term care facilities. PMID- 1919759 TI - Simplifying documentation: a nursing care plan format. PMID- 1919760 TI - Evaluation of a voluntary in-service on breastfeeding. AB - Overall, the recent "Breastfeeding Update Course for Health Professionals" was well received and successful, with the strengths outweighing the mainly minor weaknesses. This is further supported by the fact that most participants put their names and addresses on the list for the next course. This proposed course already is in the planning stages. PMID- 1919761 TI - Administrator's forum: strategic planning. PMID- 1919763 TI - How many cognitively impaired elders are eligible for home care? PMID- 1919762 TI - New directions for nursing administration research. PMID- 1919764 TI - Nurses' attitudes about nursing models in practice. PMID- 1919765 TI - Administrative prosperity: Principle II, staying hopeful. PMID- 1919766 TI - Using nurse consultants as educational preceptors. PMID- 1919767 TI - Sponsoring an NCLEX-RN review course. PMID- 1919768 TI - Registered nurses' attitudes toward the nursing process and written/printed nursing care plans. PMID- 1919769 TI - Common-sense ethics in administrative decision making. Part I, Preparatory steps. AB - This is Part 1 of two articles demonstrating the relevance of business ethics to nurse administrators as they confront value-laden issues such as the advantages and disadvantages of 10-12-hour scheduling patterns, understaffing, emerging registered nurse partnerships, and other administrative problems. Common-sense ethics can serve as the basis of just administrative decisions. The authors present a model of preparatory attitudes and behaviors. The steps that they propose do not guarantee success, but if implemented, they may facilitate the nurse administrator's management of diverse ethical issues. PMID- 1919771 TI - Financial responsibility and budget decision making. AB - The nursing budget constitutes one of the largest department budgets in most hospitals and in many cases involves managing millions of dollars. The degree to which the nurse executive has freedom to control financial resources has a major impact on the hospital's ability to compete in a rapidly changing marketplace characterized by a severe nursing shortage. Findings indicate a continuing problem with authority in matters germane to resource allocation. PMID- 1919770 TI - Establishing a screening program for abused women. AB - Estimates are that 1.8 million women are physically abused each year by their husband. Abused women are seen daily in emergency rooms, prenatal clinics, primary care centers, and inpatient units. To prevent abuse and the adverse health and economic consequences, routine assessment is essential. The authors offer a step-by-step plan to establish a successful abuse screening program. PMID- 1919772 TI - Quality assurance in rural hospitals. AB - Within the last decade there has been an expanding amount of information on quality assurance in healthcare. Despite the prolific citations on the topic, only a few address the needs and concerns regarding quality assurance programs in rural healthcare institutions. The author summarizes the more frequently expressed concerns of nursing administrators in implementing a comprehensive quality assurance program in the rural environment. PMID- 1919773 TI - Issues related to the use of nurse extenders. AB - The nursing shortage has prompted a recurring discussion about the appropriate mix of bedside care givers in nursing that can be constructed to ensure quality patient care. As nursing's role has become more professional, there has arisen a need to differentiate work tasks and develop nurse extenders. The author discusses nursing and non-nursing duties as they relate to a model of nurse extenders and related practice issues. PMID- 1919774 TI - Recruitment, retention, and compensation of agency and hospital nurses. AB - Despite the increased use and considerable cost of using supplemental nursing services, almost nothing is known about agency nurses or how they might differ from their hospital counterparts. The purpose of this study was to examine recruitment-, retention-, and compensation-related differences between agency and hospital staff nurses. The authors discuss implications for nurse administrators and provide recommendations for maximizing the work force participation of less costly part-time hospital staff nurses. PMID- 1919775 TI - Bar coding. An effective productivity concept. AB - Bar coding is becoming a major contributor to the information revolution taking place in the health-care industry. Besides improving nursing productivity, bar coding can improve the quality of documentation and enhance the manner in which staffing requirements are identified and patient classification information gathered. PMID- 1919776 TI - Working with consultants to achieve home health agency goals. AB - Should we or shouldn't we seek outside help for our home health agency organizational problem? Hiring consultants is an important consideration and can be nonproductive if proper care is not taken. Although not a panacea, the prudent choice of who, when, where, and how to use consultants can enhance the ability of managers to operate home health businesses. The authors discuss well-known reasons for client's resistance to consultants and reasons home care agencies have started to look to consultants to solve their problems. Specific guidelines for selecting and working with consultants are discussed to ensure that maximum benefit is achieved from consulting relationships. PMID- 1919777 TI - Staff participation in a strength, weakness, opportunity, and threats analysis. AB - The use of a strength, weakness, opportunity, and threats (SWOT) analysis to evaluate current and future directions can lead to the successful evolution of any organization. A SWOT analysis was performed by the multidisciplinary staff of a hospital-based home health agency. Outcomes of the SWOT analysis resulted in the establishment of department goals and objectives, as well as staff empowerment and increased cohesiveness. PMID- 1919778 TI - Nurse recruitment. From selling to marketing. AB - Nursing vacancies are many, but applicants are few. So what will motivate qualified candidates to respond to your hospital's nurse recruitment advertisements rather than to those of your competitors? An applicant-friendly marketing approach to recruitment advertising can give your hospital the competitive edge in filling those hard-to-fill nursing vacancies. PMID- 1919779 TI - Quality and cost of AIDS nursing care as a function of inpatient delivery systems. AB - Decisions to hospitalize persons with AIDS (PWAs) and the subsequent nursing process and outcomes associated with this hospitalization are of major concern to nurse administrators. Although decisions to hospitalize may be out of their control, events occurring during hospitalization that affect the quality of nursing care received are clearly the nurse administrator's responsibility. This report addresses a major issue concerning the care of PWAs: the decision to establish a dedicated AIDS unit. The effect upon both quality care and nursing care costs is discussed. PMID- 1919781 TI - AIDS no recruiting obstacle. PMID- 1919780 TI - A patient-centered framework for restructuring care. AB - Restructuring to meet patient care needs is the greatest challenge facing nursing and hospitals today. As leaders of the largest clinical discipline, nurse executives have a professional responsibility to assist hospitals to design delivery systems that will ensure high-quality care and financial viability. The author describes how one nursing division formulated its values and beliefs into a framework for practice and operationalized the framework into a patient centered care delivery system. PMID- 1919782 TI - No compulsory AIDS testing. PMID- 1919784 TI - Daily hassles cause burnout. PMID- 1919783 TI - The merit and significance of clinical nurse specialists. AB - The authors studied the merit and significance of the role of the clinical nurse specialist (CNS) by collecting quantitative and qualitative data documenting the activities performed in each of the four role components: practitioner, educator, scholar, and consultant. This follow-up study continues to substantiate the impact of the CNS role on quality patient outcomes and the major contributions of the CNS to the nursing organization and the hospital. PMID- 1919785 TI - The Perceived Conflict Scale. PMID- 1919786 TI - Nursing administration can enhance the image of the nurse. PMID- 1919787 TI - Make grand rounds a grand event. PMID- 1919788 TI - Variance analysis. Part II, The use of computers. AB - This is the second in a two-part series on variance analysis. In the first article (JONA, July/August 1991), the author discussed flexible budgeting, including the calculation of price, quantity, volume, and acuity variances. In this second article, the author focuses on the use of computers by nurse managers to aid in the process of calculating, understanding, and justifying variances. PMID- 1919789 TI - Computer reconstruction of nucleolar architecture by interactive three dimensional color display. AB - The first complete three dimensional ultrastructural reconstruction of pancreatic cell nucleoli, was done using EM and computer 3D-assisted reconstruction of serial sections with interactive 3D back-to-front and color display methods based on voxel representation. The purpose of the study was to depict the architecture of the nucleolar components. We obtained information about the location of the nucleolus within the nuclear volume and about the shape and polarity of the 3 main nucleolar territories. PMID- 1919790 TI - Structural organization of the thylakoid membrane: freeze-fracture and immunocytochemical analysis. AB - This article summarizes our ultrastructural studies on the organization of the thylakoid membrane of green algae and higher plants. We have used freeze-fracture and immunogold labeling to investigate the lateral distribution of the components in the membrane, their interactions, and the folding of their polypeptide chains in the membrane. PMID- 1919791 TI - Structural analysis of two-dimensional arrays of cholera toxin B-subunit. AB - Two-dimensional arrays of cholera toxin B-subunit (CTB) have been obtained by specific interaction with lipid films, as described by Ludwig et al. (1986). The relationship between two types of array, of either rectangular or hexagonal geometry, was analyzed using crystallographic methods of electron image analysis. Our results showed that the type of array obtained was highly dependent on the negative stain used and that both arrays presented related lattice parameters, indicating that they originated from a common unstained structure. Image analysis of hexagonal arrays at 17 A resolution revealed variable CTB projected structures, ranging from annularly symmetric particles to highly asymmetric particles, very distinct from the pentameric structure resolved from rectangular crystals. The present data suggest that hexagonal arrays result from an imperfect staining of CTB rectangular crystals. The staining distortion is such that the stain layer does not match faithfully the pentameric protein distribution whereas the regular organization of the specimen is maintained. PMID- 1919792 TI - Advantages of fast-freeze fixation followed by freeze-substitution for the preservation of cell integrity. AB - The use of fast-freeze fixation (FFF) followed by freeze-substitution (FS) has supplied new data in a variety of domains due to the rapidity of this fixation compared to the slow process of the conventional chemical fixation. FFF completely arrests all the cell's biological reactions, and physically immobilizes most molecules within a few milliseconds. This review deals with the main results we obtained concerning the preservation of organelles particularly sensitive to osmotic shock, the maintenance in situ of soluble or depolymerizable cell components, the visualization of brief transient events, and the opening up of new prospects in the field of immunocytochemical labeling. PMID- 1919793 TI - Cryo-electron microscopy of vitrified specimens: an approach to the study of bulk specimens. AB - We are using and developing cryo-electron microscopy of vitrified specimens. Our main interests concern the structure of muscle and muscular components. Micrographs which generally contain periodic features are analyzed by numerical image processing methods. To detect artifacts induced by the electron microscopy techniques, we correlate our results to those obtained by X-ray diffraction. In this paper, we describe our approach to the study of bulk specimens. Vitrification of such specimens is assessed by cryo-X-ray diffraction. Microscopy is done on cryo-substituted specimens. PMID- 1919795 TI - Biological applications of electron probe microanalysis in France. AB - The contribution of French science to the field of biological X-ray microanalysis is reviewed. The main analytical microscopy centers are listed, and their methods and main results are summarized. PMID- 1919794 TI - X-ray microanalysis of cell nuclei. AB - The principal component analysis, a multivariate statistical analysis of data, has been used to process X-ray microanalytical data from cell nuclei. Sixty-seven measurements from different areas of chromatin, nucleoli of rat follicular cells, and nucleoli of rat oocyte cells in their antral stage have been studied. The variables are the X-ray characteristic signals for P, S, Al, Fe, Cu, and Zn. This method demonstrates four distinct groups, the chromatin area, which is associated with a higher concentration of P; the compact mass of oocyte nucleolus which possesses the highest content in S, Al, and Zn, and two groups of nucleolar areas. The fibrillar component is richer in S, Al, and Zn than the granular component. The high degree of correlation between these three elements proves the chemical affinity of metals for the proteins (S being the signature for proteins). Cryoembedding in Lowicryl resin at even lower temperatures (213 degrees K in K11M) after quick cryofixation and cryosubstitution in the absence of chemical fixatives gives good ultrastructural preservation and the possibility of simultaneously performing X-ray microanalysis and immunocytochemistry. PMID- 1919796 TI - A computer program for many-beam image simulation of amplitude-contrast images. AB - A computer program for the simulation of amplitude-contrast electron micrographs is described. The program is based on the n-beam dynamical theory of diffraction contrast as described by Howie and Whelan (see Howie, A., and Whelan, M.J. (1961) Proc. R. Soc. Lond. [Biol]). The displacement fields associated with crystal lattice defects are calculated using linear anisotropic elasticity. The program can be used to simulate images of crystals containing line or planar defects or combinations of these defects. The line defects can be oriented freely within the foil, and are not restricted to being mutually parallel, but must be straight. Different techniques available for solving the diffraction problem, with or without the column approximation, are discussed. PMID- 1919797 TI - Primitive unit cell volumes obtained from unindexed convergent-beam electron diffraction patterns. AB - Provided that multiple reflection is present, a common occurrence with electron diffraction on microcrystallites, a single unindexed convergent-beam electron diffraction (CBED) pattern taken with the beam axis parallel to any direct lattice row allows the volume of the primitive cell to be calculated. The film measurements required are the diameters of the successive high-order Laue zones (HOLZ), the lengths of any two coprime vectors in the zero-order Laue zone (ZOLZ), and the angle between them. The primitive cell volume is an objective criterion allowing in a simplification in the identification of a phase under study by rapidly eliminating other possible phases. The computer program CELVOL for the calculation of the primitive cell volume from film measurements, or from literature cells, is available from the authors. PMID- 1919798 TI - High resolution biological scanning electron microscopy: a comparative study of low temperature metal coating techniques. AB - Structural information on the surface of biological specimens can be resolved within molecular dimensions by "in-lens" field emission scanning electron microscopes when cryo-methods are used to adequately preserve the native state of the specimen. The visual definition of molecular surface structures depends largely on the metal coating. The thickness of the coating, as well as the temperature at which it is deposited, are among the most important parameters affecting visual definition. These were evaluated on T4 polyheads and T4D phages using chromium double-axis rotary shadowing (DARS). Micrographs of optimally DARS coated T4 polyheads and T4D phages were compared with chromium planar-magnetron sputtering (PMS) and unidirectional shadowing with platinum/carbon. Metal deposition was carried out at low temperatures during all three procedures. Optimal visual definition of structural details on the surface of DARS coated T4 polyheads and T4D phages (capsomeres of T4 polyheads and their subunits with diameters of 8 and 3 nm; T4D phage tail fibres with a thickness of 3 nm) is achieved at a thickness of the chromium film greater than the minimum required for metal film coalescence. Chromium DARS coating at room temperature resulted in poor structural definition, whereas DARS at specimen temperatures of -85 degrees C and -150 degrees C, with the chromium thickness optimized for each temperature, yielded good visual detail of polyhead substructures. The visual definition was slightly reduced when DARS coating was carried out at a specimen temperature of 250 degrees C. Adequate structural visibility of T4D phage and T4 polyhead surface structures was achieved with the three coating techniques tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919799 TI - Possibility of use of primary antibody drop for repeated immunostaining. PMID- 1919800 TI - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the vitamin A status of Hartley guinea pigs, Sprague-Dawley rats, C57Bl/6 mice, DBA/2 mice, and Golden Syrian hamsters. AB - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic, renal, lung, and serum vitamin A levels were investigated in species/strains, which show highly variable susceptibility to TCDD toxicity. Young male Hartley guinea pigs, Sprague-Dawley rats, C57Bl/6 mice, DBA/2 mice, and Golden Syrian hamsters received single intraperitoneal doses, in the range 0.5-400 micrograms TCDD/kg body weight, aimed to produce a similar toxic and limited lethal effect in all species. Animals were sacrificed 1, 7, 14, 28, 56, and 112 days after TCDD injection. The time-related increase in hepatic vitamin A storage was inhibited by TCDD in all species studied, but the doses required to produce the inhibition were considerably varied due to species. The duration of the inhibition was dependent both on dose and species. All species, except for the guinea pig, managed to increase the liver reserves of vitamin A at the end of the study, as compared to the amount present at the time of TCDD treatment. A marked increase in renal vitamin A content, related to TCDD exposure, was observed in the rats, as opposed to a slight decrease in the guinea pigs and no effect in mice or hamsters. All species tested, except for the C57Bl/6 mouse, showed a marked TCDD related decrease in pulmonary vitamin A. The rat was the only species which showed a consistent effect (a small increase) in serum vitamin A levels, as a result of exposure to TCDD. The effects of TCDD on the hepatic and pulmonary vitamin A contents correlated reasonably well with the observed toxic response in this study. However, the correlation could not be observed for the effects of TCDD on renal, and serum vitamin A levels. PMID- 1919801 TI - Synthesis and assignment of novel [125I]-labeled 1 alpha,25-dihydroxyvitamin D3 derivatives. AB - This paper describes the synthesis and structural assignment of noval 125I-1 alpha,25-dihydroxyvitamin D3 derivatives (1a) and (1b) labeled with 125I-Bolton Hunter reagent [N-succinimidyl 3-(4-hydroxy-3-iodo[125I]phenyl)propionate] (1), which is known as a protein-labeling reagent, as tracers for radioimmunoassay (RIA). The radiospecific activities of these tracers (1a) and (1b) were calculated as 2,200 Ci/mmol (81.4 TBq/mmol). PMID- 1919802 TI - The in vitro and in vivo inhibition of protein glycosylation and diabetic vascular basement membrane thickening by pyridoxal-5'-phosphate. AB - We studied the effect of pyridoxal-5'-phosphate (PAL-P) on protein glycosylation and diabetic nephropathy in NSY mice. In experiment 1, an in vitro model of the browning phenomenon involving the incubation of lysine and glucose was inhibited by PAL-P. In experiment 2, administration of PAL-P to congenitally diabetic NSY mice markedly reduced the thickening of the glomerular basement membrane. These results suggest that PAL-P has the potential to be used for reducing the nephrotic complications of diabetes mellitus. PMID- 1919803 TI - Improvement in iron deficiency anemia through therapy with ferric ammonium citrate and vitamin C and the effects of aerobic exercise. AB - In 781 female college students, there were 41 cases of iron deficiency anemia, 209 of latent iron deficiency, 3 of other anemias, and 528 normal cases. Fifty four volunteers recruited from the iron deficiency anemia and severe latent iron deficiency groups were randomly divided into 4 study groups. Groups I and III received 500 mg of vitamin C daily, and groups II and IV received ferric ammonium citrate (FeAC; equivalent to 6 mg iron) in addition to vitamin C for 9 weeks. Groups I and II were loaded by aerobic exercise at 50% VO2 max. Significant differences between groups were noted in serum ferritin (SF) in III/IV, hematocrit (Ht) in II/III and III/IV, and reticulocytes (RET) in I/II, I/IV, and III/IV. Hemoglobin (Hb) and other iron-related blood indices tended to normalize in groups II and IV when compared with the pre-values. VO2 max was elevated in groups I and II regardless of iron treatment, but was augmented more in group II than group I. PMID- 1919804 TI - Utilization and metabolism of [U-14C]4' galactosyllactose (O-beta-D galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl-(1----4)- D-glucopyranose) in rats. AB - O-beta-D-Galactopyranosyl-(1----4)-O-beta-D-galactopyranosyl- (1----4)-D glucopyranose (designated as 4'GL) are produced from lactose with Cryptococcus laurentii OKN-4. Excretion and metabolism of 4'GL in rats were examined using a radioisotope technique. [U-14c]4'GL was synthesized from [U-14C]lactose by Cryptococcus laurentii OKN-4. The 14CO2 in expired air was counted after oral administration of [U-14C]4'GL or [U-14C]lactose in conventional rats, rats treated with antibiotics and germ-free rats. The rate of 14CO2 excretion from conventional rats given [U-14C]4'GL was slower than that from those administered [U-14C]lactose. When [U-14C]4'GL was orally administered to rats given antibiotics, there was a 2-h delay in 14CO2 excretion, as compared to conventional rats. In germ-free rats, total excretion of 14CO2 from [U-14C]-4'GL decreased to about one-third of that of conventional rats during a 24-h period. Radioactivities in the serum, liver, and carcass of the [U-14C]4'GL oral administration group were lower than those of the [U-14C]lactose oral administration group. Radioactivities in the feces and urine however, were higher in [U-14C]4'GL group than in [U-14C]lactose group. PMID- 1919805 TI - Marginal zinc deficiency and changes in behavioral salt taste threshold and salt preference in mice. AB - An animal model of marginal zinc deficiency was tested in mice, and salt taste threshold and salt preference were investigated in the state of marginal zinc deficiency. Two experiments were conducted. In Experiment 1, four-week-old male ICR mice were fed diets of three different levels of zinc content (3.17, 9.27, or 48.13 micrograms Zn/g) for 60 days. Food intake, growth, zinc levels in tissues, hepatic metallothionein (MT) content, and activities of selected enzymes (hepatic and RBC delta-amino-levulinic acid dehydratase (ALAD) and plasma alkaline phosphatase (ALP] did not differ among the groups throughout the experiment, and no overt signs of zinc deficiency were manifested in any group. In Experiment 2, four-week-old male ICR mice were fed a zinc-deficient diet (1.98 micrograms Zn/g) or a zinc-adequate diet (49.14 micrograms Zn/g) for 56 days. Food intake and growth did not differ between the two groups, and no overt signs of zinc deficiency were observed throughout the experiment. Zinc levels in the plasma and femur--but not those in the brain, kidneys, liver, and red blood cell (RBC)--and plasma ALP activities were significantly lower on Day 42 and Day 56 of the experiment in the mice fed the zinc-deficient diet (ZnD group) than in those fed the zinc-adequate diet (ZnA group). Hepatic MT contents were lower in the ZnD group than in the ZnA group on Day 56 only. Salt taste threshold was 0.05% in the ZnA group, while it was 0.1% in the ZnD group, between Day 30 and Day 38, and between Day 44 and Day 52 of the experiment. Preference for 0.9% NaCl solution was no different in the two groups when tested between Day 38 and Day 40 or between Day 52 and Day 54, but that for 1.6% NaCl solution was significantly higher in the ZnD group than in the ZnA group between Day 40 and Day 42, and between Day 54 and Day 56. PMID- 1919806 TI - The stability of thiamine and thiamine tetrahydrofurfuryl disulfide added to table wines. AB - Both thiamine hydrochloride and thiamine tetrahydrofurfuryl disulfide were added separately to table wines at concentrations equivalent to 0.3 and 1.5 microgram of free thiamine per kJ of caloric energy. The resultant mean increments in thiamine activity, measured by Lactobacillus fermenti microbiological assay after 21 months of storage, were in the range 55 to 103% of the added vitamin, indicative of high bioavailability of thiamine from this source. PMID- 1919807 TI - The behavior of L-ascorbic acid in the healing process of dorsal wounds in guinea pigs. AB - The behavior of L-ascorbic acid (AsA) in the healing process of wounds in guinea pigs was investigated by determining AsA and dehydroascorbic acid (DAsA) levels. Dorsal skin wounds of guinea pigs fed AsA-deficient diets for 10 days were surgically induced, and the animals were intraperitoneally supplemented with 0, 0.5, 5, 50 mg/day of AsA for 4 days, respectively. The animals were sacrificed, and the amounts of AsA and DAsA in healing skin wound and intact skin were determined by high-performance liquid chromatography (HPLC). It was found that total AsA levels in the healing wound of the animals in AsA-supplemented groups were almost similar to those in intact skin, respectively. However, DAsA levels in the healing wounds on day 4 of the healing period are significantly higher than those not only in the intact skin but also in the completely regenerated skin on day 14 of the healing period. From these results, it was suggested that the wound healing process was accompanied by the oxidation of AsA, moreover, the reduction of DAsA to AsA did not sufficiently occur in vivo. PMID- 1919808 TI - Effects of vitamin E-enriched egg yolk on lipid peroxidation, hemolysis and serum lipid concentration in young and old rats. AB - Effects of a diet containing different amount of vitamin E-enriched egg yolk powder on lipid peroxidation, hemolysis, and serum lipid concentration were examined in young and old rats. Young and old rats were fed experimental diets containing 5.6% or 22.5% of normal egg yolk powder, and 5.6% or 22.5% of vitamin E-enriched egg yolk powder. When young rats were fed these diets, their tocopherol concentrations in testes, heart, kidneys, and retroperitoneum fat pads increased according to the diet tocopherol contents. Lipid peroxide levels in these tissues were inversely proportional to the tocopherol concentrations. The liver and serum, however, did not show the above relationship. In the rats fed vitamin E-enriched egg yolk diets hemolysis did not increase, in contrast to those fed normal egg yolk diets. The rats fed a 5.6% vitamin E-enriched egg yolk diet had a lower serum cholesterol level than those fed a normal egg yolk diet. In old rats, one control group was used to determine initial tocopherol concentration and two other groups were fed 5.6% normal and vitamin E-enriched egg yolk diets. The vitamin E-enriched egg yolk rats showed lower weights of the body, liver, and retroperitoneum fat pads at the end of the experiment. The normal egg yolk group had atrophied testes. The tissue and serum tocopherol concentrations were increased in the vitamin E-enriched egg yolk group, whereas they were decreased in the normal egg yolk group. In the vitamin E-enriched egg yolk group, lipid peroxide, hemolysis and serum cholesterol, especially HDL cholesterol, did not increase. These results indicate that egg yolk tocopherol was absorbed and prevented lipid peroxidation and hemolysis in young and old rats, and testes atrophy in old rats. PMID- 1919809 TI - Dimethyl-beta-propiothetin, new potent resistive-agent against stress-induced gastric ulcers in rats. AB - The preventive effect of dimethyl-beta-propiothetin (DMPT) and methylmethionine at 5 mM each on stress-induced gastric ulcers in rats was compared. Gastric ulcer diseased rats were induced by the water immersion method. The ulcer index of test rats in the DMPT group was noticeably lower, compared with those in the methylmethionine and the control groups. A comparison of the activities of serum transaminases and amylase, and the amounts of various blood components in test rats claimed that the DMPT group rats were most resistive to such strain compared with the control and the methylmethionine group rats. These results indicate that DMPT is a potent preventive-agent against the stress-induced gastric ulcers in rats without any side effects. PMID- 1919810 TI - Interaction between dietary vitamin A and single oral doses of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) on the TCDD-induced toxicity and on the vitamin A status in the rat. AB - The effect of dietary vitamin A on the toxicity of 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) and the effect of TCDD on the tissue vitamin A levels in 8-week-old male Sprague-Dawley rats of variable vitamin A status, were investigated. Rats were fed purified casein based diets containing 2,000, 5,000, 8,000, or 21,000 IU of vitamin A/kg from weaning and throughout the experiment. The study was terminated 44 days after the administration of a single oral dose of 0, 15, 30, 60, or 120 micrograms TCDD/kg body wt. With this dietary regimen it was possible to obtain healthy animals of the same age with a vitamin A status that varied within a physiological range. LD50-values for TCDD could not be calculated in any dietary group due to the unexpectedly low mortality rate. The obtained data, however, suggest that low dietary intake of vitamin A impairs the ability to tolerate the lethal effect of TCDD and/or decreases the survival time. Some TCDD related effects, i.e. body weight loss, liver enlargement and decreased testes weight, were more pronounced in the groups receiving low levels of dietary vitamin A, whereas the decrease in thymus weight was as severe in all dietary groups. Exposure to TCDD had a pronounced effect on tissue vitamin A contents. The effect differed between tissues and was dependent upon the dose of TCDD and on the vitamin A status of the animal. Generally, exposure to TCDD results in the reduction of vitamin A in most organs; very likely because the capacity for vitamin A storage is diminished. The kidney is an exception because it accumulates vitamin A in response either to TCDD itself or to the altered vitamin A status which TCDD induces. Data presented in this study are not sufficient to conclude if the observed changes of tissue vitamin A contents are sufficient to explain the spectrum of morphological changes, which is typical of TCDD exposure. PMID- 1919811 TI - Novel separation and amino acid sequences of alpha and beta subunits of pig heart pyruvate dehydrogenase. AB - Pyruvate dehydrogenase was separated from pig heart pyruvate dehydrogenase complex by gel-permeation chromatography on a TSK G4000SWG column in the presence of 4 M urea, followed by chromatography on a calcium phosphate gel-cellulose column. The pyruvate dehydrogenase was further separated into two nonidentical subunits, alpha and beta, by high-performance liquid chromatography on a Synchropak CM-300 column in the presence of 8 M urea. The complete amino acid sequences of two subunits of pyruvate dehydrogenase were determined. The peptide fragments of S-carboxymethylated subunits were generated by treatment with endoproteinase Lys-C, endoproteinase Asp-N, trypsin, and cyanogen bromide. The subunits alpha and beta contain 361 amino acid residues (Mr 40,294) and 329 residues (Mr 35,787), respectively. The amino acid sequences of subunits alpha and beta in the pig were, respectively, 98 and 96% identical to those in humans. Hydropathy analysis and prediction of the secondary structure of two subunits suggest that the subunit alpha contains the thiamin pyrophosphate-binding domain and that the subunit beta contains segments with a high hydrophobicity. PMID- 1919812 TI - Metabolism of tryptophan to niacin in Saccharomyces uvarum. AB - In Saccharomyces uvarum, the effect of metabolic intermediates of the tryptophan NAD pathway on the niacin-production was investigated. Exogenously added kynurenine and 3-hydroxyanthranilic acid raised the content of total niacin of the cells 2-fold as compared to the control cells, although anthranilic acid and tryptophan were less effective. Tryptophan was taken up into the cells faster than kynurenine, and the intracellular pool of tryptophan was larger than that of kynurenine. Of kynurenine (0.05 mM) added to the medium, 55% went through the transaminase flux (2-H liberation), 20% through the kynureninase flux, but none through the acetyl-CoA flux. As for tryptophan, only 2% went through the kynureninase flux. The products through the transaminase flux were identified as kynurenic acid (85%) and xanthurenic acid. 3-Hydroxykynurenine, 3 hydroxyanthranilic acid, quinolinic acid and niacin were also detected. The metabolism of tryptophan via the kynureninase flux reached a plateau above 0.05 mM. The production of kynurenine and kynurenic acid gradually increased above 0.05 mM. Tryptophol was formed in parallel with the amount of tryptophan consumed, while the rate of niacin production increased after glucose and tryptophan were exhausted. Based on the data obtained, a possible regulatory mechanism of the tryptophan-NAD pathway was discussed. PMID- 1919814 TI - Correlation between serum concentrations of the branched chain amino- and alpha keto-acid and the distribution of the branched-chain fatty acids on rat skin surface. AB - This study described the relationship between the concentration of the branched chain fatty acid (BCFA) in rat skin surface lipid and the serum level of the branched-chain amino acid (BCAA) and branched-chain alpha-keto acid (BCKA). The concentrations of the BCFAs in the monoester fraction of the skin surface lipid, and BCAAs and BCKAs in the serum were analyzed in rats fed varying amounts of protein (0 to 40%) and different types of BCAAs (3%) for 2 weeks. The serum concentrations of BCAA were proportional to the protein level by day 10 of the feeding period. This dose response was not sustained by day 14 at the end of the feeding. Protein level dependence was not so evident in the concentration of BCKA. The concentrations of BCFA, even carbon number iso-acid in particular, increased in linear proportion to protein intake in the skin surface lipid. Supplementation of valine and isoleucine to the diet at a 3% level specifically raised the concentration of the respective BCAA and corresponding BCKA in serum, and related BCFA in the skin surface lipid. Addition of leucine, however, did not affect the related BCFA concentration in spite of elevated concentration of leucine and its alpha-keto acid. A good linear correlation between the average concentration of the substrates in the circulation and the concentrations of the product BCFA on the skin surface was thus obtained for valine, isoleucine and their respective alpha-keto acid. This relationship did not appear to hold up for leucine and its alpha-keto acid. PMID- 1919813 TI - Effect of dietary protein depletion and ethanol on demethylation and denitrosation of N-nitrosodimethylamine by rabbit liver microsomes. AB - To study how the metabolism of N-nitrosodimethylamine (NDMA) is affected by dietary protein level and chronic ethanol feeding, 24 rabbits at 18 weeks of age, assigned to four groups, each with 6 rabbits, were fed for 8 weeks on the following 4 different diets; 21% protein content containing 21.1% casein and water, 21% protein content containing 21.1% casein and 7.5% ethanol, 7% protein content containing 4.8% casein and water, 7% protein content containing 4.8% casein and 7.5% ethanol. Body weights, liver weights and microsomal protein contents in the liver were significantly smaller in 7% protein diet groups than in 21% protein diet groups. Microsomal P-450 contents per protein content were less in 7% protein diet groups than in 21% protein diet groups. NDMA demethylation activity due to non-arachidonic acid stimulated system (NASS) and NDMA denitrosation activity were greater in 21% protein diet groups than in 7% diet groups. Chronic ethanol feeding increased NDMA denitrosation activity due to arachidonic acid stimulated system in both dietary protein levels. The ratio of NDMA demethylation activity (carcinogenic action) to NDMA denitrosation activity (detoxication action) was greater in 7% dietary protein groups than 21% dietary protein groups. The value of this ratio was decreased by chronic ethanol feeding in 7% dietary protein groups. Cytotoxic and carcinogenic actions of NDMA might be enhanced by low protein diet due to inhibition of denitrosation of NDMA in liver microsome and chronic 7.5% ethanol feeding alleviates metabolic activation of NDMA to carcinogenic compounds. PMID- 1919815 TI - Cholesterol-lowering effect of Agemaki, a kind of shellfish, in mice. AB - Agemaki (Sinonovacula constricta) is an edible and popular shellfish in the western part of Japan. The present study demonstrated the effects of feeding Agemaki on cholesterol and triglyceride concentrations in mice plasma and liver. Mice were fed a diet containing 0.1% cholesterol and 0.1% Na-cholate for 1 week, and then a cholesterol-free diet or a cholesterol-enriched one for 2 weeks. To both diets, freeze-dried Agemaki was added at a 5% level. There was no statistically significant effect on the body-weight gain, food intake, and liver weight by feeding Agemaki in both dietary regimens. However, Agemaki significantly lowered the concentrations of plasma and liver cholesterol and also of plasma triglyceride in mice feeding on the cholesterol-rich diet. A similar tendency was also observed for the mice feeding on the cholesterol-free diet. The analysis of freeze-dried Agemaki revealed a relatively larger proportion of n-3 polyunsaturated fatty acids and plant sterols, which may possibly decrease plasma lipids. So far as we know, this is the first report showing hypolipidemic effect of Agemaki. PMID- 1919816 TI - Triplet pregnancy: changes in morbidity and mortality. AB - The outcome of 13 sets of triplet infants delivered between January 1, 1981, and December 31, 1988, is analyzed with specific regard to immediate neonatal morbidity. Thirty-nine viable infants were born with no perinatal deaths. Overall, 80% of triplet infants incurred some morbidity, including hyperbilirubinemia (51.3%), hypoglycemia (30.8%), respiratory distress syndrome (28.2%), respiratory compromise (23.1%), anemia (17.9%), patent ductus arteriosus (15.4%), and intraventricular hemorrhage (10.3%). All morbidities occurred in infants who averaged less than 2,000 g and 35 weeks' gestation at birth. As a background to understanding these observations, a review of reports of triplet morbidity and mortality in the United States and Europe is presented. Over the past 80 years, a continual decline in triplet perinatal mortality has occurred despite no change in the average gestational age at delivery over the past 40 years. The triplet perinatal mortality rate is now less than 10%, and prematurity is no longer as influential on perinatal mortality as it is on morbidity. Improvement in neonatal resuscitation and care and delivery by cesarean section are felt to be responsible for lower mortality rates. We believe that the optimum level of care for triplet gestations includes antenatal and neonatal care at tertiary perinatal centers and, except for special circumstances, delivery by cesarean section. PMID- 1919817 TI - Spontaneous resolution of fetal nuchal cystic hygroma. AB - Complete resolution of the hygroma occurred in two fetuses with the mid-trimester ultrasound diagnosis of a nuchal cystic hygroma. Cytogenetic studies showed a normal 46,XX karyotype in one fetus, and a 47,XX, +18 in the other. Complete regression of cystic hygroma has been reported in fetuses with normal chromosomes, as well as in those with trisomy 21, and with Turner's syndrome. The incidence of spontaneous in utero resolution of fetal nuchal cystic hygroma is unknown. The natural history of cystic hygroma in utero cannot be correlated with the chromosome complement. An antenatal karyotype determination should be offered to any patient whose fetus has cystic hygroma, even to those with spontaneous resolution. PMID- 1919818 TI - Current knowledge about skin-to-skin (kangaroo) care for preterm infants. AB - Skin-to-skin ("kangaroo") care for preterm infants is becoming widespread in Western Europe. During this care the mother holds her diaper-clad premature infant against her skin beneath her clothing and allows self-regulatory access to breast-feeding. Fathers hold their infants skin-to-skin also. Research projects in Western Europe and the United States provide data that support the safety and effectiveness of this method. Infants held skin-to-skin are warm enough and have regular heart rate and respirations, more deep sleep and alert inactivity, less crying, no increase in infections, greater weight gain, and earlier discharge. Lactation is more productive and of greater duration. Parents become attached to their infants and feel confident about caring for them. This research is summarized and annotated in a table, along with descriptive reports and videotapes. These data can be used by health care professionals to make informed decisions about offering kangaroo care opportunities to selected parents and their preterm infants. PMID- 1919819 TI - A case of glutaric acidemia type II (severe multiple acyl-CoA dehydrogenation disorder) with subsequent prenatal exclusion in a sibling. AB - A case of severe multiple acyl-CoA dehydrogenation disorder is described. This is the second such case reported to have had an elevated maternal serum alpha fetoprotein and normal amniotic alpha-fetoprotein. The child's 3-day extrauterine life was characterized by intractable acidosis, respiratory distress, and ventricular fibrillation. The characteristic biochemical, morphologic, and microscopic findings of this condition are reviewed. A subsequent pregnancy was evaluated using chorionic villus sampling and analysis of cultured trophoblasts. The trophoblasts were biochemically normal, and a normal child was subsequently delivered. Since the manifestations of this disorder developed in utero, prenatal diagnosis and therapy offer the only hope for a more prolonged survival. PMID- 1919820 TI - Blood pressure patterns in the first three days of life. AB - Current blood pressure data for healthy newborn infants consist primarily of single measurements of systolic and diastolic pressure in the first 48 hours of life. The purpose of this study was to determine if blood pressure levels are stable or are changing during the first few days of life. To determine blood pressure level and trend, indirect blood pressure was measured on day 1 through day 3 of life in all infants admitted to the well newborn nursery at Hahnemann University Hospital in Philadelphia. Systolic pressure correlated significantly with birthweight on day 1 of life (P less than .03). Repeated measures analysis of variance demonstrated a significant increase in both systolic and diastolic pressures over the first 72 hours of life (P less than .001). There was no difference in blood pressure among racial groups (black, Hispanic, white, Asian). In healthy newborns, there was no correlation of blood pressure with maternal conditions: toxemia, diabetes, substance abuse. These data demonstrate that blood pressure correlates with birthweight in well newborns. There is, however, a significant progressive increase in both systolic and diastolic blood pressure over the first 3 days of life, regardless of birthweight or maternal conditions. PMID- 1919821 TI - Long-term subcutaneous terbutaline tocolysis: report of possible neonatal toxicity. AB - Terbutaline is a beta-sympathomimetic agent that has gained wide use in obstetrics as a tocolytic agent. In addition to inhibiting uterine contractions, terbutaline can cause other clinically significant beta-mediated effects. Terbutaline readily crosses the placenta, and both fetal and neonatal toxicity have been reported. We report possible cardiovascular toxicity secondary to long term prenatal terbutaline exposure involving three preterm infants of a quadruplet pregnancy. The infants developed cardiovascular decompensation with bradycardia, metabolic acidosis, poor tissue perfusion, and decreased urine output. The infants' conditions were resistant to all routine interventions but responded well to dobutamine infusion. We theorize that long-term prenatal beta mimetic exposure led to downregulation of fetal beta-receptors. This resulted in impaired myocardial function, increased peripheral vascular resistance, and poor cardiac output. We suggest that neonates with a history of prenatal exposure to terbutaline should be observed closely after birth for any evidence of cardiovascular deterioration. PMID- 1919823 TI - The incidence of meconium-stained amniotic fluid from 1980 through 1986, by year and gestational age. AB - The annual incidence of meconium-stained amniotic fluid was analyzed for changes in a total obstetric sample of 45,115 singleton, vertex, liveborn infants over a 7-year study period. The incidence of meconium-stained amniotic fluid for the total obstetric population was calculated for each year of the study period. The sample was then stratified by estimated gestational age, and the incidence of meconium-stained amniotic fluid was calculated for each gestational age group. The incidence of meconium-stained amniotic fluid increased 40.9% over the study period, from 18.8% in 1980 to 26.5% in 1986 (P less than .001). This increase was found to be in a consistent linear trend (P less than .05). The incidence of meconium-stained amniotic fluid was also found to increase significantly in a linear trend as gestational age of the fetus increased. These findings lend support to both the maturational theory and the stress theory of meconium passage in utero. PMID- 1919822 TI - The use of intravenous immunoglobulin (IVIG) to prevent infections in bronchopulmonary dysplasia: report of a pilot study. AB - The incidence and severity of pneumonia, sepsis, and other infections was evaluated in a group of 30 premature infants with moderate to severe bronchopulmonary dysplasia (BPD), half of whom were randomly treated with intravenous immunoglobulins (group A). The patients were treated until the age of 6 months. They were compared with an untreated control group (group B). The number of pneumonic episodes (5 in group A and 15 in group B) and other infections, excluding sepsis (1 in group A and 7 in group B), were significantly reduced in the treated group (P less than .05). The number of episodes of sepsis, suspected sepsis, and necrotizing enterocolitis were similar in the two groups. The decrease in the number of respiratory and other infections in BPD infants treated with IVIG requires verification by a larger trial. PMID- 1919824 TI - A comparative study of variables differentiating false labor from early labor. AB - False labor is a common and frustrating problem for women and health-care providers. The purpose of this study was to compare characteristics of true and false labor. A convenience sample of 65 women compared data for three groups who were observed for labor including: false labor, women who were dismissed and returned in true labor more than 48 hours later, impending labor, women who were dismissed but returned in true labor 48 hours or less later, and early labor, women who were admitted for true labor directly following an observation period. Psychosocial differences among the groups were measured by the Maternal Adjustment and Maternal Attitudes (MAMA) scale and a semistructured interview schedule. Chart reviews were conducted to measure physiologic differences and perinatal outcomes. Descriptive and inferential statistics were computed using the SPSSX program. The following variables were statistically significant at P less than .05 for false labor: somatic scores on the MAMA scale, contraction frequency, cervical Bishop scores, gestational age, and Apgar scores. Increased frequency of abnormal labor patterns, intervention with amniotomy, and oxytocin augmentation were observed in false labor subjects. The negative emotional responses of women who were interviewed suggest a need for further investigation of interventions to promote both physical comfort and psychological support. PMID- 1919825 TI - Cervical cerclage in early pregnancy. AB - A retrospective review of 33 patients who underwent transvaginal cervical cerclage for the treatment of an incompetent cervix from June 1984 through July 1987 was conducted. A total of 38 transvaginal cerclages were placed. For the purposes of comparison, the patients were divided into three groups according to gestational age at the time of cerclage: group 1 less than or equal to 13 weeks; group 2 greater than 13 weeks, but less than 18 weeks; group 3 greater than or equal to 18 weeks. There was no difference among groups in mean age, gravidity, history of diethylstilbestrol exposure (DES), prior pregnancy loss at or before 20 weeks, or prior dilation and curettage procedure. There were 24 modified McDonald and 14 modified Shrodkar procedures performed. The mean gestational age of cerclage placement in group 1 was earlier than in group 2 and group 3 by 3.5 and 10.5 weeks, respectively. There were no major surgical complications in any of the three groups. The overall incidence of preterm labor and preterm birth were 48.6% and 37.8%, respectively. Analysis of variance demonstrated a trend toward differences in the incidence of preterm labor, preterm birth, and estimated gestational age at delivery, with the earlier group favored. None of these, however, reached the level of statistical significance. Estimated blood loss, obstetric complications, mean birthweight, and mean gestational age at delivery were not statistically different for the three study groups. The above data are discussed and support given for the safety and efficacy of cervical cerclage placement in early pregnancy when compared with the more standard recommendations of placement at from 14 to 17 weeks' gestational age. PMID- 1919826 TI - Strategies for change: nursing implementation of the birthing room. AB - Nurses were primary participants in introducing the birthing room for maternity care in their respective institutions. Based on tape-recorded interviews, this paper is a report on how the idea of a birthing room was initiated, the resistance it encountered, the eight strategies used to implement the idea, and appropriation of the idea by physicians. Although the examples are specific to the development of a birthing room, the strategies can be used by nurses to initiate other changes in perinatal health care delivery. In addition, increased collaboration between nurses and physicians may make some strategies obsolete. PMID- 1919827 TI - Alternative method of gestational age assessment by the measurement of human erythrocyte differentiation antigen expression. AB - Standard estimates of gestational age are dependent on such subjective data as maternal recollection of last menstrual period, ultrasound examination of the fetus, and the postnatal physical and neurological examination (Ballard score). We hypothesized that a quantitative, objective laboratory test using flow cytometric analysis of erythroid differentiation antigens could be useful to predict gestational age. For this study erythrocyte samples were obtained within 24 hours of birth from 25 infants (gestational ages 20 to 41 weeks) who met the criteria that traditional estimates of gestational age, such as the Ballard score, fetal ultrasound, and maternal estimate of last menstrual period all agreed within 1 week for the assessed infant's gestational age. Study measurements included reticulocyte count and determination of the percentage of erythrocytes that expressed the 5F1 and 20.3 erythropoietic differentiation antigens. Linear regression analysis indicated that the best correlations with gestational age were reticulocyte count (R2 = .354) and the reciprocal of the percentage of erythrocytes expressing the 5F1 antigen (R2 = .470). When both variables were incorporated into a linear regression model, the predictability of gestational age achieved an R2 = .608. Through this study we have established the feasibility and methodology of using fetal and newborn erythrocytes to provide an objective assessment of gestational age by flow cytometric analysis of erythroid differentiation antigen expression. This methodology will allow for an independent assessment of gestational age when fetal blood sampling is performed for other prenatal diagnostic studies. Further investigation is needed to identify other erythroid differentiation markers that would improve the accuracy of our model to predict gestational age. PMID- 1919828 TI - Ethical context for physician refusal of requested treatment. PMID- 1919829 TI - Conversion of fetal tracing from equivocal to chronic in a patient with subsequent cerebral palsy. PMID- 1919831 TI - Ventilatory management casebook. Resuscitation in hydrops fetalis. PMID- 1919830 TI - Perinatal ultrasound casebook. Antenatal findings in congenital hypophosphatasia. PMID- 1919832 TI - Fetal heart rate monitoring casebook. Fetal heart rate monitoring and severe placental abruption. PMID- 1919833 TI - Unusual presentations of fetal teratoma. AB - Teratomas are the most common congenital neoplasm. Fetal intracranial teratomas generally are large solid/cystic tumors that often completely replace normal brain tissue. Mediastinal teratomas are uncommon and rarely result in nonimmune hydrops fetalis. We describe two unusual presentations of fetal teratoma. The first is a fetus with massive hydrocephalus and marked facial deformities that were caused by a small intracranial teratoma. The second is a fetus with a mediastinal teratoma associated with non-immune hydrops fetalis. In both cases, compression by the mass resulted in lethal sequelae. PMID- 1919834 TI - Abnormal fetal presentation or lie. PMID- 1919835 TI - Perinatal perspective: the NPA forum. Access to care, Part 3. PMID- 1919836 TI - Spatial summation properties of directionally selective mechanisms in human vision. AB - Our goal in this paper was to measure psychophysically the receptive-field size of motion units in human vision. To this aim, length and width spatial summation functions were measured for drifting (8-Hz) sinusoidal gratings of spatial frequencies 0.1, 1.0, and 10.0 cycles per degree (c/deg) with two threshold criteria: direction discrimination and simple detection. For each spatial frequency, contrast sensitivity for detection of the direction of drift increased with increasing stimulus size (length or width), at first rapidly (slope greater than or equal to 1.0) and then more gradually (slope 0.29). For most stimuli, the detection and direction-discrimination contrast thresholds were nearly the same. However, for stimuli severely curtailed in width, significantly more contrast was required for direction discrimination than for detection. These results were predicted with a summation model, which incorporated three-dimensional (space space-time) linear input filters, and probability summation over space and among different filter types. The fit of the model gave an estimate of both the receptive-field length and width of motion-detector units in human vision. At each spatial frequency, the estimates of receptive-field width and length were similar, indicating that the receptive fields of motion-detector units are as long as they are wide at all spatial scales. Receptive-field size varied from approximately 0.12 cycle at 0.1 c/deg to 0.52 cycle at 10.0 c/deg. PMID- 1919837 TI - Two-dimensional spatial and spatial-frequency selectivity of motion-sensitive mechanisms in human vision. AB - Thresholds for detecting the direction of motion of drifting (8-Hz) vertical gratings [of spatial frequencies 0.1, 1.0, and 10.0 cycles per degree (c/deg)] were measured in the presence of masks that varied in both spatial frequency and orientation. Masks with different temporal properties were used. The specificity of masking was also measured for a stationary test grating of spatial frequency 3.0 c/deg. After suitable scaling and transformation, the masking data gave an estimate of the two-dimensional spatial-frequency tuning surface of cortical detector units in human vision. With the assumption of small-signal linearity and zero phase, the tuning surfaces were inverse Fourier transformed to give an indication of the size and structure of the psychophysical receptive fields of detector units. The results obtained with drifting test gratings and jittering (random phase) mask gratings indicate that motion-detector receptive fields increase in size (in cycles) with increasing spatial frequency but, at all spatial scales, have a length-width ratio of 1. These results are in close agreement with the summation results reported in J. Opt. Soc. Am. A 8, 1330 (1991). Using the same jittering mask stimuli and stationary test gratings, we confirm reports by Daugman [Vision Res. 24, 891 (1984)] and Harvey and Doan [J. Opt. Soc. Am. A 7, 116 (1990)] that motion-independent units have elongated receptive fields with a length-width ratio near 1.8. We conclude that the receptive fields of motion-dependent and -independent mechanisms in human vision are fundamentally different. The possibility that the orientation selectivity of a motion unit is sharpened by its selectivity for direction of motion is discussed. PMID- 1919838 TI - Effect of luminance on suprathreshold contrast perception. AB - Perceived contrast was measured under natural viewing conditions with the use of contrast-matching and magnitude-estimation paradigms and found to be independent of luminance over a range of luminances from 37.5 down to 8 cd/m2. However, this contrast constancy broke down when the dimmer target was below 8 cd/m2. The perceived contrast of the dimmer target then fell below that expected from contrast constancy. The extended range of contrast constancy previously reported [J. Physiol. 252, 627 (1975); Vision Res. 16, 1419 (1976)] has been thought to imply neural mechanisms with unlimited constancy, but these researchers permitted differential adaptation to the brighter and dimmer targets, which were seen haploscopically (by different eyes). As our natural-viewing procedure ensured that both bright and dim targets were presented to retinal areas in a roughly constant state of adaptation, our failure to find extended contrast constancy implies an important limitation on the neural processing of contrast. PMID- 1919839 TI - Evidence of proteoglycan/proteoglycan interactions within aggregates. AB - Nonaggregated proteoglycan monomers, digested fragments of the monomers, as well as link proteins have been shown to self-associate. These associations have not been shown to occur on the aggregate. However, previous reports, using the Kleinschmidt technique of monolayer electron microscopy, have noted proteoglycan subunits on the aggregate that appear to interact, either as branched proteoglycans or as proteoglycan subunits that appear to share the same attachment site on the hyaluronic acid chain. Branching and shared attachments were noted in all aggregates analyzed in this study. Increasing the average space between proteoglycan subunits on the reconstituted aggregate resulted in a significant decrease in branched proteoglycans, indicating either a weak association occurring on the aggregate, or an artifact created by a three dimensional structure being reduced to a two-dimensional monolayer image. The shared attachments were independent of both the presence of link proteins and changes in spacing between proteoglycans, suggesting a proteoglycan-proteoglycan interaction occurring before aggregation. The interactions were not influenced by proteoglycan concentration at the time of aggregation. Link proteins, however, did increase the number of proteoglycans on the aggregate that could be cross linked with a bifunctional reagent, suggesting that link proteins facilitate proteoglycan-proteoglycan interactions. PMID- 1919840 TI - Vascular assessment of the periarticular ligaments of the rabbit knee. AB - While the rabbit is being extensively utilized in animal models for orthopaedic research, the vascular anatomy of the knee ligaments has not been thoroughly described in this species. This study demonstrates the blood supply to the infrapatellar fat pad, the cruciate ligaments, the medial collateral ligament (MCL), and the menisci, such that the effects of manipulating these tissues may be properly interpreted. Vascular injection with India ink and iodinated i.v. contrast dye was performed in 11 New Zealand white rabbits, and routine histology done on six. The large vessel anatomy is similar to that described for humans and dogs, with a descending geniculate artery, medial and lateral superior and inferior geniculate arteries, a posterior geniculate artery, and a recurrent anterior tibial artery. The microvascular anatomy is also similar in that the infrapatellar fat pad and synovial membrane are highly vascular, the menisci are vascularized from their periphery (being avascular centrally), and the medial collateral ligament is relatively well vascularized. A difference from dogs and humans is present in the anterior cruciate ligament (ACL), which is poorly vascularized, with a single artery on its anterior aspect. High magnification histologic evaluation reveals numerous capillaries in the substance of the MCL, while the ACL is nearly devoid of such vessels. The interspecies variation in vascular anatomy is a variable that must be taken into consideration in any surgical or traumatic animal model investigation of knee pathology. PMID- 1919841 TI - Elimination of exogenously injected sodium-hyaluronate from rabbit flexor tendon sheaths. AB - To obtain information about the elimination of Na hyaluronate (NaHe) deposited in flexor tendon sheaths in rabbits, two flexor tendon sheaths from each hind limb were operatively exposed in 15 animals and each filled with one of four different NaHe preparations, namely: 10 mg/ml, MW 2.6 x 10(6); 10 mg/ml, MW 6.3 x 10(6); 19 mg/ml, MW 3.0 x 10(6); and 19 mg/ml, MW 6.5 x 10(6). One, 3, and 7 days after surgery, the NaHe concentration was measured in frozen specimens from the tendon sheaths. One day after surgery, NaHe concentration in the tendon sheath fluid was close to 10 mg/ml in all groups. Three and 7 days after surgery it was higher in tendon sheaths in which NaHe preparations with a high (19 mg/ml) rather than with a low concentration (10 mg/ml) had been deposited. At 3 days, NaHe concentration was also higher in sheaths that had received a preparation with a high MW (6.5 x 10(6)) than those with a lower MW (2.6 or 3.0 x 10(6)). The findings suggest that within the first 24 h, a dilution of concentrated NaHe preparations takes place, probably as a result of their hyperoncotic properties. After 24 h, there was a slower decline in NaHe concentration when more concentrated solutions (19 mg/ml) and solutions with high MWs (6.5 x 10(6)) were administered. Development of pharmaceutical NaHe preparations with slow elimination from tendon sheaths should reasonably be focused on a solution with a high MW and high concentration. PMID- 1919842 TI - Mechanical characteristics of the stem-cement interface. AB - The mechanical characteristics of the interface between a metallic stem and the surrounding poly(methyl methacrylate) bone cement were determined from experimental tests and finite element analyses. Push-through-stem tests of straight and tapered titanium alloy stems, surrounded by cement columns, were performed and the resulting load-displacement behavior and strain distribution on the surface of the cement column were measured for loading, unloading, and reloading. Test geometries were modelled using nonlinear, axisymmetric, finite element analyses, which incorporated Coulomb friction elements at the titanium alloy-cement interface. Initial residual stresses, due to curing of the cement column, were modeled by thermal contraction of the cement. Good agreement was obtained between load-displacement curves and surface strains predicted from the nonlinear analysis and those obtained from experiments, when a coefficient of friction of 0.3 was assumed for the stem-cement interface. These results show that, in the absence of chemical adhesion, the load-displacement behavior of a stem-cement composite can be described completely in terms of the friction at the interface and the residual stresses normal to the interface. PMID- 1919843 TI - Remodelling of bone around intramedullary stems in growing patients. AB - The remodelling of bone around intramedullary cemented stems, used for the fixation of massive distal femoral replacements in young patients, has been studied. Several types of remodelling have been identified, and this is common to all of the retrieved specimens that have been in situ for periods of 6 to 18 months. Transection of cortical bone and the insertion of a massive prosthesis leads to (a) the formation of a pedicle of bone or bony bridge that grows from the transection site over the shaft of the prosthesis, (b) bone resorption at the transection site, (c) the development of an inner porotic cortex surrounding the intramedullary stem and subperiosteal bone formation, and (d) a shell of bone around the acrylic cement. The tibial component that allows continued growth of the proximal tibial physis consists of a press fit metallic plateau with a stem that slides into an ultra-high-molecular-weight polyethylene sleeve inserted below the growth plate. A sclerotic layer of bone forms adjacent to a soft-tissue interface around both the sleeve and the metallic component. Remodelling of bone around intramedullary stems is attributed either to a redeveloping blood supply or to load adaptive changes. PMID- 1919844 TI - Changes in tibial bone mass after primary cementless and revision cementless total hip arthroplasty in canine models. AB - The purpose of this study was to examine right-left differences in tibial bone mass after unilateral (left) cementless total hip arthroplasty (THA). Of 39 dogs with THAs, 9 had primary cementless porous-coated femoral stems for 6 months and 15 had similar stems for 2 years. Five dogs had aseptically failed cemented hips, and 10 had aseptically failed cemented hips that were revised with cementless porous-coated femoral stems (5 without bone graft and 5 with autogenous bone graft). These animals were sacrificed 6 months after the revision surgery. The primary cementless dogs showed no right-left difference in tibial bone mineral content (BMC) or cortical bone cross-sectional geometry after 6 months, but after 2 years there was a distal right-left difference in BMC of 6% caused by expansion of the medullary canal in the tibia of the operated limb. Tibial BMC was more than 20% lower in the operated limb of the failed cemented dogs, approximately 15% lower in the nongrafted group, and 7% lower in the grafted group. The right left tibial difference in BMC in the 2-year primary cementless group is most probably because of subclinical disuse of the operated limb. Among the dogs with failed cemented stems, the lower right-left difference in the two revised groups compared with the non-revised group suggests that improved limb function after cementless revision THA may cause gain of previously lost bone. PMID- 1919845 TI - In vivo flexion/extension of the normal cervical spine. AB - Twenty-two women (age range 25-49 years, average 30.9 years) and twenty-two men (age range 23-42 years, average 31.6 years), all healthy and asymptomatic, underwent passive flexion/extension examinations of the cervical spine. Functional x-rays were taken and analyzed using a computer-assisted method that quantified intervertebral rotations, translations, and locations of the centers of rotation for each level C1-C2-C6-C7. The aim of the study was to establish values for these parameters for a normal population as related to age and gender. In the process, a statistically significant difference was found in the average value of rotation between male and female groups at the C5-C6 level. A new parameter, the ratio between translation and rotation, was also established and may prove useful for clinical diagnoses. This parameter has a smaller error associated with it than do pure translations and may aid the clinician by helping to account for the large variation in rotatory ranges of motion within the population. This translation/rotation ratio indicated highly significant differences in the lower segments of the cervical spine between gender groups. PMID- 1919846 TI - Bone graft translation of four upper cervical spine fixation techniques in a cadaveric model. AB - The goal of spinal fixation is to promote bony fusion by restricting motion at the site of the bone graft. Therefore, in order to evaluate the efficiency of various cervical fixation techniques, we determined the translations at the posterior arch of C1 for four C1-C2 posterior techniques: Gallie, Brooks, Magerl, and Halifax. Our model was the cadaveric specimen, with extensive soft tissue injury: transection of the alar, transverse, and capsular ligaments. Under three dimensional physiological loading, we recorded the motion of C1 relative to C2, and calculated the translations at the surface of the graft in three dimensions, 10 specimens being tested intact, injured, and instrumented with each of the techniques. We assumed that translational laxity or neutral zone was the critical motion parameter and evaluated it, quantified herein as the neutral zone, at seven points at the graft site. The three-dimensional neutral zone translations were analyzed by their axial and shear components. We found that there was no significant difference with the fixation techniques in the average axial translation (Brooks: 1.1 mm; Magerl: 1.3 mm; Gallie: 1.5 mm; and Halifax: 0.5 mm). In shear, the Magerl averaged 1 mm, which was significantly less than the Gallie (2.1 mm). The Brooks (1.6 mm) and Halifax (1 mm) were not different from each other, Magerl, or Gallie. We propose that evaluation by translational laxity (neutral zone) at the graft site is a noteworthy concept in biomechanical analysis. PMID- 1919848 TI - Effects of indomethacin on demineralized bone-induced heterotopic ossification in the rat. AB - Indomethacin inhibits bone formation when treatment is initiated before the implantation of demineralized bone matrix (DBM). For the inhibition of bone induction to occur, indomethacin treatment had to be initiated 6 h or more before implantation of DBM. Initiating the drug treatment at or after the time of DBM implantation had no effects on the amounts of new bone formed. The inhibition by indomethacin is dose related over a range between 0.04 and 4 mg/kg body weight. Recovered day-1 DBM implants, transplanted into indomethacin pre- and posttreated syngeneic rats, formed bone at the same rate as controls did. However, recovered day-1 DBM implants lyophilized before transplantation showed decreased bone formation but significant dystrophic calcification as judged by a lower alkaline phosphatase activity and an elevated calcium content. PMID- 1919847 TI - Proliferation and macromolecular synthesis by rat calvarial bone cells grown in various oxygen tensions. AB - Perinatal rat calvarial bone cells were isolated by sequential collagenase digestion and grown in oxygen tensions ranging from 1 to 60% O2. Cell proliferation as determined by automated cell counting and DNA content was greatest in the lower oxygen tensions (less than or equal to 9% O2), whereas alkaline phosphatase activity and [35S]sulfate and [14C]proline incorporation were greatest in the higher oxygen tensions (greater than or equal to 13% O2). It is concluded that lower oxygen concentrations favor bone cell proliferation, whereas higher oxygen concentrations favor macromolecular synthesis. These findings, when related to the known pO2 of the fracture callus, suggest the following sequence of events: first, at the time of fracture an ingrowth of osteoprogenitor cells, capillary buds, and primitive mesenchymal cells occurs in the fracture site, a region of low pO2; second, a great increase in cellular proliferation accompanied by an initiation of macromolecular synthesis follows; finally, as the pO2 levels begin to increase, cellular proliferation decelerates, accompanied by an increase in macromolecular synthesis. PMID- 1919849 TI - Regional blood flow and strontium-85 incorporation rate in the rat hindlimb skeleton. AB - Regional distribution of radioactive microspheres and 85Sr incorporation rate in the os ilium, femur, and tibia were determined in 44 rats. In 15 additional animals, regional blood flow was measured with the reference sample technique. Highest numbers of microspheres were found in the distal femoral and proximal tibial metaphyses. Highest blood flow rates were found in the os ilium, the caput femoris, and distal femoral and proximal tibial metaphyses. The diaphyses and epiphyses of the femur and tibia had a relatively lower perfusion. The regional 85Sr incorporation rate was correlated (r = 0.67) to the regional distribution of the microspheres. The dispersion of the data was large and this was mainly due to biological variation. The results describe the regional distribution of blood flow in the rat hindlimb and demonstrate a close association between blood flow and mineral turnover in normal rat skeletal tissue as shown by the correlation between microsphere and 85Sr incorporation rate distribution. PMID- 1919850 TI - Effects of propranolol on bone metabolism in the rat. AB - Propranolol, a nonspecific beta-blocker has many physiologic effects. Its effects on bone in vivo are unknown, although beta receptor sites have been found on osteoblasts. In this study, the hypothesis tested was that low doses of propranolol could alter bone properties and enhance orthotopic endochondral bone formation. In a group of nonsurgical rats, propranolol treatment increased femoral torsional strength on biomechanical testing. In the rat surgical model used, right femora were fixed to a polyethylene plate and then defects were created mid-diaphysis and subsequently filled with demineralized bone matrix. These rats (defect rats) were randomly divided into groups that were given propranolol or a saline carrier for 19 consecutive days. In the defect rats, increased trabecular femoral metaphyseal mineral apposition rates were observed in propranolol-treated groups. Densitometry and roentgenographic scoring of callus formation after 12 weeks in propranolol-treated rats revealed increased callus and bone union. The results of this study indicate that propranolol treatment can significantly affect bone properties. PMID- 1919851 TI - Postfracture irradiation effects on the biomechanical and histologic parameters of fracture healing. AB - The effects of single-dose local irradiation on the biomechanical properties of closed femoral fractures were studied in 75 mature Sprague-Dawley rats. Ten days after fracture, the rats were irradiated with 900 rads at 250 kV to the entire fractured femur. At 2, 3, 4, 8, and 16 weeks after fracture, both fractured and contralateral intact femurs were recovered and evaluated biomechanically by testing to failure in torsion. Results were compared with those from a similar study involving fractures irradiated 3 days after fracture as well as nonirradiated control fractures. Fracture healing progressed faster when irradiation was delayed 10 days than when delayed 3 days, and control fractures healed more rapidly than after either delay. In the 10-day delay group, fractures showed greater strength than did those in the 3-day delay group at 8 weeks, but the strength of irradiated fractures in both groups was similarly depressed at 16 weeks, with a maximum torque well below that of control fractures. These results suggest that delaying radiation exposure of a fracture may mitigate short-term deleterious effects on fracture repair, but that long-term results may be similar to those associated with expeditious irradiation. PMID- 1919852 TI - The effects of ischemia on long bone vascular resistance. AB - An in vitro canine tibia model was used to assess the effects of 48 h of hypothermic (4 degrees C) ischemia on bone vascular resistance and on responsiveness of intraosseous blood vessels to circulating norepinephrine. Three groups of bones were studied: Group I (n = 11), 48 h hypothermic ischemia; Group II (n = 11), 48 h hypothermic ischemia with pretreatment with allopurinol and oxypurinol; and Group III (n = 10), no ischemia. Resting vascular resistance in both ischemic groups (79 and 74 mmHg/ml/min) was significantly higher (p less than 0.0001) than in the nonischemic group (22 mmHg/ml/min). Effects of norepinephrine on vascular resistance were significantly greater in both ischemic groups (p less than 0.004). In all three groups, acetylcholine infusion attenuated the increases in perfusion pressure caused by norepinephrine. This demonstrates secretion of endothelial-mediated relaxing factors (EDRF) and prostaglandin for up to 48 h of hypothermic ischemia. As no significant differences were detected between the two ischemic groups, this study failed to demonstrate any protective effect of xanthine oxidase inhibitors. PMID- 1919854 TI - Telopeptide-depleted bovine skin collagen as a carrier for bone morphogenetic protein. AB - The telopeptide of type I collagen is thought to be responsible for causing immunogenic response when introduced into xenogenic hosts. To eliminate this problem, solubilized bovine skin collagen was filtered through a millipore membrane, digested repeatedly with pepsin to remove telopeptides, and used as a carrier for a water-soluble, partially-purified fraction of bone morphogenetic protein (BMP) in mice. Composite implants of this telopeptide-depleted collagen and the partially-purified BMP fraction consistently elicited ectopic bone formation in mice 3 weeks postimplantation. When implanted alone, collagen or BMP failed to show this response. Collagens, prepared by use of conventional methods (acid-solubilized collagen, or collagen-digested once with pepsin) were also assessed as carriers for BMP, but were found to be inferior in terms of consistency of bone formation and amount of induced bone mass. The results suggest that telopeptide-depleted collagen permitted a gradual release of purified BMP for induction of bone, with minimal immunogenic interference. Consequently, this collagen carrier represents an important development for future clinical application of BMP. PMID- 1919853 TI - Response of cortical bone to local controlled release of sodium fluoride: the effect of implant insertion site. AB - In a previous experiment, sodium fluoride in a biodegradable polymer matrix was introduced into the femoral canal of the rabbit and bone formation was compared with contralateral controls. We noted significant bone formation, but only in the distal third of the periosteal surface of the femur. This experiment was performed to distinguish fluoride-induced periosteal bone formation from that due to the reactive osteogenic changes associated with local injury caused by the process of implantation. A proximal approach on the right leg and a distal approach on the left were used for the insertion of the implants in rabbits. Femurs were removed after 30 days and tested for stiffness and load to failure. The cross-sectional area of mineralized bone was determined at proximal, midshaft, and distal locations. Fluorescent bone tissue growth labels were injected at weekly intervals to measure the rate of new periosteal bone formation. The results were compared with a control group that received sham implants. Results showed no difference between measured properties in right and left femurs in the control group or in those exposed to fluoride. A significant increase was found in the fluoride group in load to failure, along with cross sectional area of mineralized bone, and periosteal growth rates compared with the control group, but no difference was seen in stiffness. No difference was detected between the response proximally and distally in the fluoride group regardless of the location of insertion. There were no detectable changes in serum fluoride level after implantation of the poly L-lactic acid/sodium fluoride matrix. These results show that fluoride exerts its osteogenic effects equally at proximal, midshaft, and distal regions of diaphyseal bone and is uninfluenced by the site of local injury due to insertion of the implant. PMID- 1919855 TI - Electromagnetic stimulation of bone repair: a histomorphometric study. AB - The effect of pulsing electromagnetic fields (PEMFs) on bone repair was studied in principal metacarpal bones of eight adult male horses: Six horses were treated with PEMFs, and two horses were untreated. In treated horses, Helmholtz coils were applied during a 60-day period to the left metacarpal bones, bored with eight holes of equal diameter and depth, from the middiaphysis toward the distal metaphysis. Eight equal holes bored in the right metacarpal, surrounded by unactivated Helmholtz coils, were taken as controls. The two untreated horses were taken as additional control. The results of computer-assisted histomorphometric analysis indicate that (a) in diaphyseal levels, the amount of bone formed during 60 days is significantly greater (p less than 0.01) in PEMF treated holes than in contralateral ones and those in control horses; (b) in metaphyseal levels, PEMF-treated holes are sometimes more closed, sometimes less, as compared with contralateral holes and those in control horses; in any case the statistical analysis indicates that the symmetry in the rate of hole repair, found between the two antimeres of control horses, is not appreciable at metaphyseal levels also; (c) there was no statistically significant difference between untreated holes in PEMF-treated horses and holes in control horses, neither at diaphyseal nor at metaphyseal levels. These preliminary findings indicate that PEMFs at low frequency influence the process of bone repair on both diaphysis and metaphysis, and seem to improve the process of bone repair in skeletal regions normally having a lower osteogenetic activity, i.e., in diaphyses as against metaphyses. PMID- 1919856 TI - Computational methods for analyzing the structure of cancellous bone in planar sections. AB - Conventional stereologic methods for expressing the orientation of anisotropic materials are limited to materials assumed to possess orthogonal directions of orientation. In many substances, including cancellous bone, this assumption is unsubstantiated. Presented here are two simple methods for characterizing the orientation of any anisotropic material within a plane. By modeling the substance as a series of lines oriented in particular directions, it is possible to arrive at either a "phase distribution" that expresses the degree of orientation distributed over a range of angles or a series of "primary orientations" that express the degree of orientation at a select number of angles, with an additional measure of the degree of isotropy. This characterization of anisotropy is highly dependent on such parameters as feature size, sample size, test line spacing, and test line width. Given the careful selection of these parameters, the new methods provide simple measures of orientation, which may prove useful in testing Wolff's trajectorial theory of the relationship between mechanical stresses and the orientation of cancellous bone. PMID- 1919857 TI - [Simultaneous recording of vocal cord vibrations by ultrasound laryngography and photoelectroglottography]. AB - A newly developed ultrasonic laryngeal imaging system, ultrasound laryngography (ULG), can record vocal cord vibrations by the simultaneous use of high-speed M mode, ultrasonic pulse transmissions, and the other methods. The purpose of this study was to compare normal male vocal cord vibrations simultaneously recorded by ULG at several pitches and loudness with those obtained by photoelectroglottography (PGG). The open quotient (OQ), speed quotient (SQ), and speed index (SI) were measured by these two methods. While only relative glottal area can be obtained by PGG, exact glottal width can be obtained by ULG. So the mean opening/closing velocity as well as the mean opening/closing steepness of the vocal cord vibration plot were measured by ULG. The results are summarized as follows: 1) The OQ, SQ, and SI values measured by these two methods were very similar. There was a trend for greater mean values in these parameters as measured by ULG compared with those determined by PGG. 2) This difference was presumed to be due to (1) vocal cord phase differences in horizontal and vertical components, (2) the location of the light source and that of photosensor from the glottis, and (3) ULG beam width in relation to vertical movements of the vocal cords. 3) Glottal width curve obtained by ULG was asymmetrical triangular wave because closing phase was shorter. By ULG observation, as voice loudness increased, opening/closing steepness became greater and closed phase longer, while closing phase shorter. The waveform obtained by ULG was presumed to be relatively similar to glottal flow waveform because there was a trend of more asymmetrical triangular waveform obtained by ULG than those obtained by PGG. In conclusion, ULG is the only method to be able to obtain exact glottal width compared with the other glottography, and this method is considered to be useful for the investigation of the vocal cord vibrations. PMID- 1919858 TI - [Electrophysiological study on pathophysiology of Bell's palsy--distribution of nerve conduction velocities (DNCV) in facial nerve with collision method]. AB - The etiology of Bell's palsy is still obscure, but the hypothesis that hypoxia and compression of the nerve induced by edema in the Fallopian canal are the main causes of Bell's palsy is widely accepted. Tojima (1988) reported that the motor nerve conduction velocity (MCV) gradually decreased as degeneration of the nerve fibers progressed in Bell's palsy. The majority of facial nerve fibers are myelinated, and the greater the fiber diameter, the faster the conduction velocity. For this reason, Tojima suggested that Wallerian degeneration in Bell's palsy would begin from the thicker myelinated fibers. The measurement of MCV, however, reveals only the activities of the fastest velocity motor nerve fiber in the nerve trunk. This weak point can be resolved by measurement of the distribution of nerve conduction velocities (DNCV), which was introduced by Hopf in 1962 as the collision method. In the present report, the DNCV of facial nerve was measured using the collision method to estimate the distribution of the diameter of nerve fibers in normal subjects and patients with Bell's palsy and to elucidate the pathophysiology of Bell's palsy. The subjects were 14 normal adults (19 measurements) and 14 patients with Bell's palsy who visited our university clinic within 7 days to 18 days after onset, with no other complications such as diabetes. Results obtained are as follows. 1) The mean DNCV in 14 normal subjects (19 measurements) was unimodal, showing a peak at 20 to 22 m/s. 2) In DNCVs of patients with Bell's palsy, loss of thicker fibers with faster conduction velocity was recognized (11/14, 79%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919859 TI - [Changes of glucose uptake in vestibular and auditory nuclei induced by high perilymphatic potassium ion concentration--autoradiographic study]. AB - Characteristic nystagmus could be provoked by introducing potassium ion into the unilateral perilymphatic space of healthy guinea pigs. At first, irritative nystagmus appeared for some time to the K+ introduced ear side, and then, it was followed by paralytic nystagmus which directed to the non introduced ear side. During this experiment, the excitabilities of the vestibular nuclei and the central auditory nuclei were investigated by [14C] deoxyglucose method. In the period of "irritative nystagmus", the increment of glucose uptake in the ipsilateral vestibular nucleus, especially in the superior, median and inferior part, was noticed more significantly than the contralateral vestibular nucleus. On the other hand, the period of "paralytic nystagmus" showed the significant increment of glucose uptake in all parts of the contralateral vestibular nucleus. As to the excitability of the central auditory nuclei, the significant decrement of glucose uptake, which was noticed in all periods of this experiment, was predominant in the ipsilateral cochlear nucleus and other superior auditory nuclei of the contralateral side. PMID- 1919860 TI - [Secondary malignant tumors of the temporal bone. A histopathologic study and review of the world literature]. AB - Metastatic involvement of the temporal bone by malignant tumors is considered to be rare. The actual incidence of metastatic temporal bone tumors, however, is probably much higher than suggested by reports in the literature. The reason for this is that histologic studies are rarely performed on temporal bones in routine postmortem examinations of patients with possible metastatic disease. Also, in patients with multiple metastatic lesions, otologic complaints and signs may often be overshadowed by other more disabling symptoms. Twelve temporal bones were histopathologically examined from 6 patients who had metastatic temporal bone disease from various primaries and the results obtained in our present series of 6 cases were: 3 cases of hematogenous dissemination from a distant primary (a hepatic cell carcinoma, a bronchogenic squamous cell carcinoma, and an adenocarcinoma of unknown primary); 2 cases of direct invasion from adjacent head and neck tumors (squamous cell carcinomas of the eyelid and hypopharynx); and one case of diffuse metastatic leptomeningeal carcinomatosis (a transitional cell carcinoma of the renal pelvis). Among these, to our knowledge either hepatic cell carcinoma or renal pelvis carcinoma metastatic to the temporal bone has not been reported previously in the world literature. We reviewed the previously published reports of metastatic temporal bone tumors and found that there were 212 reported cases cited in the literature and that the most common sites of origin in order of frequency were breast, lung, pharynx, kidney, and prostate. Our temporal bone study and literature survey reveal that there are three distinct routes of tumor spread from the primaries to the temporal bone: 1) hematogenous dissemination from a distant primary, 2) direct neoplastic extension from adjacent areas, and 3) diffuse metastatic leptomeningeal carcinomatosis (DMLC). Our study also indicates that in most cases temporal bone symptoms appeared late in the course of disease, but in some cases the otologic symptoms were an initial sign of tumor, which was particularly conspicuous in the cases of DMLC. In the cases of hematogenous dissemination, the metastatic lesion tends to be overlooked or undiagnosed because occult metastases are relatively common or, when symptomatic, the otologic symptoms often resemble the features characterized by a severe form of mastoiditis. In the cases of direct neoplastic invasion, on the other hand, recognition of temporal bone involvement is usually simple since the primary disease is quite evident. Although metastatic temporal bone malignancies are rare, otologist should always be aware of existence of this disease entity in clinical practice.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1919861 TI - [Influence of neck vibration on body sway]. AB - To investigate the influence of the cervical input to the equilibrium, the effect of neck vibratory stimulation on body sway was analyzed in 49 normal human subjects. Body perturbations during standing posture were recorded by a force platform with or without vibratory stimulus on the upper cervical region, and analyzed by computer. During the neck vibratory stimulation, the center of gravity was shifted to the forward, and the amplitude of the body sway was increased especially along the front-rear axis. These results indicate that the proprioceptive inputs from the cervical receptors largely modifies the body equilibrium in normal subjects. PMID- 1919862 TI - [Ultrastructural abnormalities of the cilia in human nasal epithelia]. AB - Nasal mucosal cilia were observed with electron microscope in 14 patients with immotile cilia syndrome (ICS), 9 with nasal papilloma (NP), 23 with sinobronchial syndrome (SB), 2 with sinusitis combined with dextrocardia (SC), 1 with Kartagener's syndrome (KS), and 5 normal controls (C). Abnormalities such as complex cilia, cilia with abnormal axonemes and cilia with randomly oriented central microtubules were frequently found in the groups of ICS (8.1%) and NP (10.4%) while less in other groups: SB (4.9%), SC (5.3%), KS (4.7%) and C (3.9%). The percentage of cilia with defective dynein arms (DA) was the highest in the ICS group (94.0%), followed by the groups of SC (53.7%), SB (47.5%), NP (41.2%), C (35.8%) and KS (33.3%). The ICS group was found to be the largest in the number of defective DA per a cilium (4.1), followed by the groups of NP (1.0), SB (0.6), SC (0.7), KS (0.4) and C (0.4). Increased rates of defective DA were also recognized in cilia of tracheal mucosa and flagella of sperm in 7 patients with ICS examined. In conclusion, neither abnormal cilia nor defective DA of cilia are specific findings for ICS. However, when we observe these findings in high percentage in nasal mucosa as well as in other organs, we may define this condition as ICS. PMID- 1919863 TI - [The localization and production of interleukin-1 in pharyngeal epithelium]. AB - Interleukin-1 (IL-1) has been thought to be one of the essential cytokines mainly produced by macrophage. The function of IL-1 are not only activates T lymphocytes, but also regulates immune responses to several antigens and effects on local and systemic immune reactions. Recently, it is reported that epidermal keratinocytes produces IL-1, and attention has been paid to local immune reaction mediated with this cytokine. In this study, we performed immunohistochemistry and immunoblotting on the pharyngeal epithelial keratinocytes and we evaluated the production of IL-1 by these cells. Pharyngeal mucous membrane of each region reacted strongly against anti-IL-1 alpha antibody, on the contrary, anti-IL-1 beta antibody comparatively only weakly. Strong reactivity was often observed on the basal layer, then it was seemed that some important relationship exists between the production of IL-1 and maturation of pharyngeal keratinocytes. Infiltration of T-lymphocytes was observed in proportion to the increase of epithelial reactivity against IL-1. There seemed to be no correlation between expression of HLA-DR antigen on keratinocytes and reactivity of IL-1. In immunoblotting study, the 31kD band, intracellular immature molecule, was identified besides 17 and 52kD. From this finding, it was suggested that IL-1 is derived from pharyngeal keratinocytes. In conclusion, the present study is helpful for well-understanding of local cellular immunity of pharyngeal mucous membrane. PMID- 1919864 TI - [Electron microscopic study on inner ear barotrauma: with emphasis on the cochlear damage]. AB - In order to investigate inner ear barotrauma, guinea pigs were subjected to rapid decompression between 2 absolute pressure (ATA) and 1 ATA in a chamber. After pressure loading and observation for absence of Preyer's reflex, they were sacrificed immediately, 1 day, 1 week and 1 month later, respectively. Then, morphological changes of the organ of Corti and stria vascularis were studied under TEM and SEM. The immediate features noted were fracture of stereocilia with minimal intracellular changes. One day later, there was marked degeneration of outer hair cells and expansion of supporting cells. The damage to stereocilia clearly preceded morphological alterations within hair cell bodies and cannot be interpreted as arising secondary to hair cell degeneration. Most of outer hair cells eventually disappeared and were replaced by supporting cells. Inner hair cells degenerated slowly; 1 month later, some of them remained almost intact, despite disappearance of stereocilia. The continuity of reticular lamina was maintained not only immediately but also through the period of hair cell degeneration, thus preventing any leakage of endolymph into the organ of Corti. There was reversible dendritic swelling of inner hair cells immediately following the trauma. No changes of stria vascularis were observed over passage of time. The mechanism of hair cell damage due to inner ear barotrauma is presumed to be a deformity of the organ of Corti caused by pressure discrepancy between perilymph and endolymph resulting in an injury to stereocilia. PMID- 1919865 TI - [Retropharyngeal hematoma following a bruise of head and neck--a case report and review of literature]. AB - Diseases affecting the retropharyngeal space are relatively uncommon, much less a case of retropharyngeal hematoma. However, a space-occupying lesion in this area can be life threatening and require emergency surgical intervention. There have been 46 cases of retropharyngeal hematoma reported in the English literatures from 1934 to 1989, but there has been no reported case in Japan. Recently we treated a 72-year-old male sustained retropharyngeal hematoma following a bruise of head and neck. The patients was received tracheostomy, antibiotic therapy and intravenous hyperalimentation, and this hematoma was resolved in about 2 weeks. The etiologies, diagnosis, therapies in our case and prognoses of the literature reviewed 47 cases of retropharyngeal hematoma were discussed comprehensively. PMID- 1919866 TI - [The difference between response of nasal mucosa to specific antigen and non specific stimulation]. AB - To examine the difference between response of nasal mucosa to specific antigen and that to non-specific stimulus in the same patient, specific nasal provocation was performed using the house dust antigen disk while nasal respiratory resistance was continuously measured by Rhinograph. On the other hand, non specific nasal provocation was performed with inhalation of methacholine while nasal respiratory resistance was continuously measured with Astograph. Thereafter the resulting response curves were analyzed. Subjects were 12 males and 9 females, who had nasal obstruction, watery rhinorrhoea and sneeze, and were proved to have allergic rhinitis by house dust. To analyze specific response curve, primary nasal respiratory resistance (Rrs.N), reacting time (Ta) and slope signifying increase of nasal respiratory resistance (delta Rrs.N) were used as parameters. To analyze non-specific response curve, primary nasal respiratory resistance (Rrs.N.cont), minimum dose of methacholine that caused an increase of nasal respiratory resistance (Dmin.N) and slope signifying increase of nasal respiratory resistance (Sd.N) were used as parameters. Ta and Dmin.N reflect sensitivity of nasal mucosa. Their values become smaller, it means sensitivity of nasal mucosa becomes higher. Delta Rrs.N and Sd.N reflect reactivity of nasal mucosa. Their values become larger, it means reactivity of nasal mucosa becomes larger.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919867 TI - Koch's postulates revisited. PMID- 1919868 TI - Necrotizing myopathy in critically-ill patients. AB - Skeletal muscle wasting is commonly observed in critically-ill patients and has been attributed to catabolic fibre atrophy and to neuropathy. This study describes the occurrence of a necrotizing myopathy in 15 out of 31 critically-ill patients who had percutaneous biopsies taken from the tibialis anterior muscles. While most cases showed necrosis of isolated fibres, 5 of the 12 patients who had serial biopsies showed progressive necrosis of up to 95 per cent of the fibres. One other case showed infarction and one case had staphylococcal vasculitis. Atrophy of type 1 and/or type 2 fibres was documented by morphometry in 12 cases. Myoglobin-containing casts were demonstrated immunohistochemically in renal tubules on either biopsy or necropsy material in 5 out of 7 cases. The presence of muscle necrosis was a clinically unexpected finding which may contribute to weakness, complicate the interpretation of tissue biochemistry and energy balance studies, and potentiate renal failure. The necrosis is probably multifactorial in origin, with ischaemia and sepsis contributing factors. PMID- 1919869 TI - Infantile desmoid-type fibromatosis. Morphological features correlate with biological behaviour. AB - It is generally agreed that the biological behaviour of infantile desmoid-type fibromatosis is unpredictable in terms of the likelihood of local recurrence. We evaluated the prognostic importance of the number of slit-like blood vessels with a mean diameter of less than 20 microns and of the quantity of undifferentiated mesenchymal cells. In addition, we studied the immunophenotypic characteristics of the proliferating cells and their nucleolar organizer region (AgNOR) numbers and distribution. Statistical analysis showed that the tendency to recur locally was correlated with larger numbers of slit-like blood vessels and undifferentiated mesenchymal cells. The proliferating cells were identified by immunohistochemistry as myofibroblasts. No correlation was found between AgNOR numbers and clinical course of the disease. We conclude that histological features easily evaluated by conventional light microscopy provide useful information on the possible course of infantile desmoid-type fibromatosis. PMID- 1919870 TI - Phenotypic analysis of malignant lymphoma in simian immunodeficiency virus infection using anti-human antibodies. AB - Primates infected with simian immunodeficiency virus (SIV) develop a condition similar to the human acquired immunodeficiency syndrome (AIDS). The close resemblance between the simian acquired immunodeficiency syndrome (SAIDS) and the human disease has led to the widespread use of SIV-infected monkeys as an animal model in the study of acquired immunodeficiency. We have investigated the use of standard anti-human antibodies for the immunohistochemical analysis of formalin fixed, paraffin-embedded tissues from monkeys with SAIDS. With the exception of antibodies UCHL1 (CD45RO), MT1 (CD43), 4KB5 (CD45RA), and Ber H2 (CD30), our routine (human) lymphoma panel of markers worked successfully on the animal tissues. Using the anti-human antibodies, we were able to analyse the phenotypes of two cases of malignant lymphoma arising in a study group of 26 SIV-infected rhesus monkeys. Both of the cases stained with the antibodies WR16 (CD45RA) and L26 (CD20), and the B-cell lineage of the lymphomas was confirmed by the detection of IgA lambda immunoglobulin expression in one case, and IgM heavy chain in the other. We therefore report the successful use of anti-human antibodies in the immunohistochemical analysis of lymphomas arising in non-human primates infected with SIV. PMID- 1919872 TI - Appendiceal carcinoids and pulmonary tumourlets. PMID- 1919871 TI - Irreversible damage to the medullary interstitium in experimental analgesic nephropathy in F344 rats. AB - Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla. PMID- 1919873 TI - Photosensitized production of singlet oxygen by merocyanine 540 bound to liposomes. AB - The production of singlet oxygen by merocyanine 540 was studied in dimyristoyl phosphatidylcholine liposomes using two singlet oxygen probes: 9,10 anthracenedipropionic acid (water soluble) and 9,10-dimethylanthracene (liposoluble). Upper and lower limits of singlet oxygen quantum yield for bound merocyanine 540 were determined to be 0.055 and 0.015 respectively. The diffusion characteristics of singlet oxygen were examined using the isotropic enhancement effect of D2O and the inhibitory effect of sodium azide. It was shown that 1O2 spent more than 87% of its lifetime in a vesicle environment. When the singlet reacting substrate and the dye were both located in the bilayer, approximately 40% of the singlet oxygen remained in the liposomes where it was originally generated. PMID- 1919874 TI - Phthalocyanine-sensitized lipid peroxidation in cell membranes: use of cholesterol and azide as probes of primary photochemistry. AB - Various phthalacyanine (Pc) derivatives of phototherapeutic interest have been shown to be efficient type II (singlet oxygen, 1O2) sensitizers in aqueous and non-aqueous solutions. However, primary Pc photochemistry in biological environments, e.g. cell membranes, has not been studied in a definitive manner. To address this question, we used endogenous cholesterol in the erythrocyte ghost as a mechanistic reporter lipid Membranes sensitized with chloroaluminum Pc tetrasulfonate (AlPcS) and exposed to white light at 10 degrees C underwent lipid peroxidation, as indicated by the accumulation of hydroperoxides and thiobarbituric acid reactivity. Specific analysis of cholesterol photo-products by thin layer chromatography and high performance liquid chromatography revealed the presence of 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide (5 alpha OOH), with much smaller amounts of 3 beta-hydroxycholest-5-ene-7 alpha hydroperoxide (7 alpha-OOH) and 5 alpha-cholest-6-en-3 beta, 5-diol and cholest-5 en-3 beta, 7 alpha-diol (5 alpha-OH and 7 alpha-OH). Identification of 5 alpha OOH as a major photoproduct provides unambiguous evidence for large scale 1O2 intermediacy. Azide inhibited lipid peroxidation in a dose-dependent fashion, providing additional support for a type II mechanism. However, the 1O2 quenching constant from Stern-Volmer analysis was approximately 50 times lower than that determined for a non-membrane probe, lactate dehydrogenase. The latter value agreed with literature values. A probable explanation is that membrane-bound dye generates most of the 1O2 involved in lipid peroxidation. Although azide can intercept any 1O2 escaping into (or formed in) the medium, it has limited access to 1O2 generated on the membrane and reacting (or being quenched) near its site of origin. PMID- 1919875 TI - Time-dependent decrease in sunscreen protection against chronic photodamage in UVB-irradiated hairless mouse skin. AB - To determine the time dependence of sunscreen protection against chronic photodamage in hairless mice, the time was varied (0-8 h) between topical sunscreen treatment and UVB radiation exposure. Sunscreen products with labeled sun protection factor (SPF) values of 2, 4 and 8 were evaluated; these values were verified in a guinea pig model for SPF determinations. When applied immediately prior to UVB radiation exposure, these sunscreen products were very effective in prevention of skin wrinkling and tumor formation. Onset of photodamage was delayed, the delay being greater with higher SPF values. However, the sunscreen actives were rapidly lost from the skin surface, and their protective effect diminished strikingly as the time between treatment and irradiation increased. For daily protection against chronic photodamage, this suggests a need for photoprotectants with greater substantivity to achieve a high level of protection throughout the day. PMID- 1919876 TI - The origin and meaning of the term "photodynamic" (as used in "photodynamic therapy", for example). PMID- 1919877 TI - Challenges for photodynamic therapy in the treatment of gastrointestinal tumours. PMID- 1919878 TI - Briefing outside JPB. Photocarcinogenesis. PMID- 1919879 TI - Science of bottle feeding. PMID- 1919880 TI - Exploration for physicians of the mature minor doctrine. AB - The "mature minor doctrine" is the common-law rule that allows an adolescent who is mature to give consent for medical care. Ethical decisions regarding consent and confidentiality should be distinguished from legal requirements. Recent court decisions have altered the law, especially in regard to consent for refusal of life-sustaining treatment. There are statutory exceptions to the rule of parental consent regarding emergency care, sexually transmitted diseases, drug treatment, mental health care, pregnancy, contraception, and emancipation. A detailed analysis of the mature minor exception is presented, utilizing court case vignettes. There is minimal legal risk in allowing adolescents older than 14 years of age to give consent for treatments entailing small degrees of risk, when they can make adultlike decisions and demonstrate signs of maturity. PMID- 1919881 TI - Usefulness of scanning procedures for diagnosis of fever of unknown origin in children. AB - During a 5-year study period, 109 patients were referred to a large children's hospital for evaluation of prolonged fever of unknown origin, defined as temperature greater than or equal to 38 degrees C (100.4 degrees F) for 3 weeks or longer and negative findings on initial examination. A two-phase protocol of outpatient followed by inpatient diagnostic studies was instituted for most patients. Confirmed diagnoses were achieved in just 36 of these children (33%) in the following disease categories: infectious, 24 (22%); autoimmune, 7 (6%); and neoplastic, 2 (2%). Scanning or special procedures and the number with positive results (in parentheses) were as follows: abdominal ultrasonography, 43 (8); abdominal computed tomography, 14 (3); indium scan 11 (5); gallium scanning, 4 (1), upper gastrointestinal tract series, 13 (2); technetium bone scanning 15 (2); bone marrow examination, 16 (1); and cranial computed tomography, 7 (0). These studies rarely led to an unsuspected diagnosis. It appears most appropriate in evaluating fever of unknown origin in children to obtain only basic laboratory studies such as a complete blood cell count, urinalysis and culture, chest radiograph, tuberculin skin test, and, in the older child, an antinuclear antibody titer. When these test results are negative, almost all children can be observed clinically for progression of illness or a focus that might then direct specific diagnostic procedures. PMID- 1919882 TI - Glycemic response to sucrose-containing mixed meals in diets of children of with insulin-dependent diabetes mellitus. AB - Our pilot study compared the short-term glycemic effects of a traditional "sucrose free" diet (Suc-Free, 2% total calories from sucrose) to a sucrose containing diet (Suc-Con, 10% total calories from sucrose) in a clinical research center. Both weighed diets were isocaloric and included 50% carbohydrate, 30% fat, and 20% protein in three meals and three snacks; glucose, fructose, and dietary fiber were identical. Sucrose isocalorically replaced complex carbohydrate at each meal and for the afternoon snack. Ten children (7 to 12 years of age; mean total hemoglobin A1 level 8.9 +/- 0.3%) were randomly assigned, in a crossover design, to one of the two orders (Suc-Free followed by Suc-Con or Suc-Con followed by Suc-Free) for consecutive 2-day diet periods; insulin doses remained constant. Preprandial and postprandial blood glucose levels were measured for each meal and snack (18 measurements per day). To account for baseline differences, we calculated the change in blood glucose levels from baseline to 30 minutes and 1 hour for each meal and snack (mean +/- SEM). No differences were detected between diets. Total area under the glucose response curve (levels measured hourly from 8 AM to 9:30 PM in milligrams per deciliter) was not significantly different for the two diets (Suc-Free 3672 +/- 240; Suc-Con 3574 +/- 285; p = 0.74). No difference in 24-hour urinary glucose levels (measured in grams per day) was detected between the two diets (Suc-Free 35.6 +/- 7.5; Suc-Con 34.5 +/- 7.5; p = 0.84). Incidences of hyperglycemia that required supplemental short-acting insulin and of mild hypoglycemia were similar for both diet periods. Thus, in a controlled setting and during a short study period, children with insulin-dependent diabetes mellitus had a similar glycemic response to diets with and without a moderate amount of sucrose. PMID- 1919883 TI - Adequacy of energy intake among breast-fed infants in the DARLING study: relationships to growth velocity, morbidity, and activity levels. Davis Area Research on Lactation, Infant Nutrition and Growth. AB - Breast-fed infants grow less rapidly after the first 2 to 3 months of age than current standards. The DARLING study (Davis Area Research on Lactation, Infant Nutrition and Growth) was designed to evaluate whether this pattern should be considered "faltering" or is a normal outcome even under optimal conditions. Data on intake, growth, morbidity, activity, and motor development were collected longitudinally from infants who were breast fed for at least 12 months. Gross energy intake, calculated from 4-day records of milk and food intake at 3, 6, 9, and 12 months, averaged 91.4, 84.1, 86.7, and 91.8 kcal/kg per day, respectively, well below recommended amounts of metabolizable energy. Nevertheless, infants usually left some food unconsumed. Growth velocity was also below current reference data and was weakly correlated with energy intake. There were no significant negative associations between energy intake at any time and incidence, prevalence, or duration of any category of morbidity during the subsequent 3 months. There were no consistent associations between energy intake and activity level, time spent sleeping, or achievement of key developmental milestones. Similarly, infants with slower growth velocity were just as active and were ill no more often in subsequent months than infants who were growing more rapidly. Thus the deviation from current recommendations for energy intake and growth can be considered a normal pattern with no apparent deleterious consequences in our population of breast-fed infants. PMID- 1919884 TI - Evaluation of the erythrocyte protoporphyrin test as a screen for elevated blood lead levels. AB - To study the effect of lowering the definition of an elevated blood lead level on the performance of the erythrocyte protoporphyrin screening test and the number of children who would require follow-up, we collected laboratory data from a screening program. The estimated sensitivity of an erythrocyte protoporphyrin level greater than or equal to 35 micrograms/dl for identifying children with elevated blood lead levels was 73% when we used 1985 Centers for Disease Control guidelines (elevated blood lead level greater than or equal to 25 micrograms/dl). Eight percent of the tests showed positive results. When we redefined an elevated blood lead level as greater than or equal to 15 micrograms/dl, the sensitivity estimate was reduced to 37% and the number of positive test results increased fourfold. PMID- 1919885 TI - Cholesterol screening in childhood: sixteen-year Beaver County Lipid Study experience. AB - To determine the extent to which cholesterol measured in childhood is predictive of values in adulthood, the investigators conducting the second follow-up of the Beaver County Lipid Study tracked the cholesterol values of 295 adults who had initially participated as children (ages 11 to 14 years) in a countywide school screening program. The follow-up study was conducted 16 years after the initial study, when the participants had reached a mean age of 28 years. The overall correlation (r) between baseline (1972-1973) total cholesterol values and the values found at the present follow-up was 0.44 (p less than 0.0001). Women had a higher correlation (r = 0.51) than men (r = 0.38). In addition, the efficacy of childhood screening for cholesterol levels was assessed by considering currently recommended borderline values (greater than 175 mg/dl (4.6 mmol/L) for children and greater than 200 mg/dl (5.2 mmol/L) for adults) as a "positive" test result. The sensitivity of screening at age 12 years for predicting elevated adult total cholesterol concentrations was 63%, specificity was 67%, and the predictive value of a positive test result was 47%. Comparison of false-positive results (above the borderline cutoff point as a child but not as an adult) and false-negative results (below the borderline cutoff point as a child but above it as an adult) showed that male subjects with false-positive results smoked significantly less than those with false-negative results (p less than 0.05) and had a greater improvement during the preceding 7 years in cholesterol-lowering dietary practices (p less than 0.01). Female subjects with false-positive results smoked significantly less than those with false-negative results (p less than 0.05), were less overweight (p less than 0.05), and had a lower prevalence of oral contraceptive use (p less than 0.01). These results support the potential value of screening for hypercholesterolemia in childhood on a population basis. Although some subjects were misclassified as a result of childhood screening, some of this misclassification was associated with adopting changes that a screening and intervention program would be designed to promote--nonsmoking, weight control, and a prudent diet. PMID- 1919886 TI - Serum cholesterol levels during and after Kawasaki disease. AB - Serum total cholesterol and high-density lipoprotein (HDL) cholesterol concentrations were studied in paired sera from 23 patients (16 boys) with Kawasaki disease (KD) during acute illness and in 35 patients (21 boys) 5.4 to 7.7 years after KD. Total cholesterol and HDL cholesterol concentrations were significantly lower (paired t test, p = 0.0001) in samples taken within 30 days of the onset of illness (3.32 +/- 0.85 mmol/L (128 +/- 33 mg/dl) and 0.54 +/- 0.25 mmol/L (20.8 +/- 9.7 mg/dl) than in the second samples taken 2 to 16 months after onset of disease (4.16 +/- 0.93 mmol/L (161 +/- 35 mg/dl) and 1.24 +/- 0.35 mmol/L (47.2 +/- 13.9 mg/dl). The lowest total cholesterol levels were observed in samples taken 6 to 9 days after the onset of KD (p = 0.019). No correlations were seen between the highest erythrocyte sedimentation rate, C-reactive protein, or thrombocyte counts and the acute or convalescent cholesterol levels. In patients studied 5.4 to 7.7 years after recovery from KD, the mean total cholesterol concentrations were still lower than in healthy Finnish children. In girls the HDL cholesterol concentrations were similar, whereas 3 of the 18 boys studied had HDL cholesterol values more than 2 SDs below the mean for healthy boys. There was no correlation between the serum cholesterol concentrations and coronary artery abnormalities. These data lead us to infer that KD does not cause such permanent changes in cholesterol metabolism as to be considered a risk factor for atherosclerosis beyond that caused by the disease itself. PMID- 1919887 TI - Reduced plasma C-20 and C-22 polyunsaturated fatty acids in children with phenylketonuria during dietary intervention. AB - The fatty acid composition of plasma and erythrocyte lipids was analyzed in 15 children with phenylketonuria (aged 3 to 12 years) during dietary treatment aimed to maintain plasma phenylalanine levels at less than 8 mg/dl (485 mumol/L), and compared with those of 12 matched control subjects. The diet of children with phenylketonuria provided less protein, with a very low proportion of animal proteins, less fat, but a higher proportion of linoleic acid as a percentage of calories, and a higher carbohydrate content versus that in the diet of control subjects. The children with phenylketonuria had higher plasma levels of oleic acid but lower levels of arachidonic (n-6) and n-3 fatty acids. Linoleic and eicosatrienoic (n-9) acid levels were the same in both groups. These changes in patients with phenylketonuria resemble those observed in vegetarians and may be due to the absence of preformed arachidonic acid and long-chain n-3 fatty acids in the phenylketonuric diet. PMID- 1919888 TI - Pulsatile growth hormone secretion in peripubertal patients with chronic renal failure. Cooperative Study Group on Pubertal Development in Chronic Renal Failure. AB - The pubertal growth spurt has been associated with changes of physiologic pulsatile growth hormone (GH) secretion, and abnormalities of the central regulation of GH release have been found by pharmacologic testing in patients with chronic renal failure. To assess the characteristics of GH pulsatility in chronic renal failure and their relationship to pubertal growth, we studied spontaneous nighttime GH plasma profiles in 80 patients (61 boys) aged 10 to 20 years receiving conservative treatment (n = 29) or dialysis (n = 18) or after renal transplantation (n = 33). Tanner genital stages 1 to 4 in boys and breast stages 1 to 3 in girls were represented. Growth hormone pulse analysis was performed by the PULSAR algorithm. Growth hormone concentration profiles were pulsatile in each patient. Growth hormone mean and baseline levels and pulse amplitudes were higher in patients receiving conservative or dialysis treatment than in patients who had undergone renal transplantation. Peak frequency was similar in all treatment groups in boys but higher in girls who had undergone transplantation than in girls receiving conservative or dialysis treatment. Growth hormone peak amplitude and mean levels were lowest in patients in late puberty. The physiologic elevation of GH amplitudes around midpuberty was observed in boys receiving conservative and dialysis treatment but not after transplantation. Growth hormone mean and baseline levels were positively correlated with plasma androgen levels in boys. Growth hormone peak amplitude was correlated with 6-month height velocity after transplantation but not in patients receiving conservative treatment or dialysis. A strong inverse relationship was observed between GH peak amplitude and corticosteroid dosage in patients undergoing transplantation. The lack of relationship between circulating GH levels and growth in patients receiving conservative or dialysis treatment is compatible with end-organ hyporesponsiveness to GH. Pubertal growth failure despite successful transplantation appears to be related to steroid-induced GH hyposecretion. PMID- 1919889 TI - Sucrose in the diet of children with insulin-dependent diabetes mellitus. PMID- 1919890 TI - Fentanyl, fads, and folly: who will adopt the therapeutic orphans? PMID- 1919891 TI - Chlamydia pneumoniae (strain TWAR) isolated from two symptom-free children during evaluation for possible sexual assault. PMID- 1919892 TI - Treatment of chronic cryptosporidial infection with orally administered human serum immune globulin. PMID- 1919893 TI - Growth status and growth rates of a varied sample of low birth weight, preterm infants: a longitudinal cohort from birth to three years of age. AB - To obtain follow-up growth data on a large sample of low birth weight, preterm infants, 985 infants were monitored longitudinally in an eight-site collaborative program until 3 years of age, corrected for prematurity. The growth of 608 of these infants was described previously through 1 year of age. In the full sample, 149 infants weighed less than or equal to 1250 gm at birth, 474 between 1250 and 2000 gm, and 362 between 2000 and 2500 gm. Thirty-three percent were white, 53% were black, and 11% were Hispanic. Weight, length, and head circumference were measured at birth and at 40 weeks and 4, 8, 12, 18, 24, 30, and 36 months gestation-corrected age in at least 862 infants each time. Descriptive statistics and estimated growth rates for all growth variables and a body mass index (height in kilograms per square meter), plotted by sex and birth weight group, demonstrated growth patterns lower than published standards for term infants of the same age and sex. These patterns of growth differed by birth weight group. Little catch-up was noted by the 36-month examination for gestation-corrected age for any birth weight group. We conclude that low birth weight, preterm infants have different patterns of growth than term infants during the first 3 years of life, even with plotting corrected for gestational age. PMID- 1919894 TI - Risk factors for major neurodevelopmental impairments and need for special education resources in extremely premature infants. AB - The purpose of this cohort study was to determine the incidence of and risk factors for major neurodevelopmental impairments among survivors of extreme prematurity. The study cohort comprised 100 infants born between 24 and 28 weeks of gestational age at one tertiary center from 1983 to 1984. Twenty-five infants (25%) died; 75 (75%) survived until follow-up (mean, 60 months). Standardized neurodevelopmental and psychometric assessments were performed in blind fashion on 68 of the 75 surviving children (91% follow-up). Informal assessments (parent, teacher, and physician reports) were obtained instead for seven (9%) children who had relocated outside of the area. Overall, 19 children (25%) had one or more major impairments: mental retardation, 9; cerebral palsy, 4; multiple impairments, 5; and blindness, 1. Despite a high prevalence of impairments, 95% of children (n = 71) were functionally independent [corrected]. Special educational resources were definitely necessary for seven (9%) and possibly needed for 36 (48%) additional children. Univariate analyses revealed four significant risk factors for cerebral palsy: hydrocephalus (relative risk = 12.2), grades III and IV intraventricular hemorrhage (relative risk = 5.8), 5 minute Apgar score lower than 7 (relative risk = 5.7), and bronchopulmonary dysplasia (relative risk = 5.5). Hydrocephalus was the only significant risk factor observed for mental retardation (relative risk = 5.4). Risk factors predicting a need for special education resources included sepsis (relative risk = 24.9), low socioeconomic status (relative risk = 16.3), and nonwhite race (relative risk = 3.0). Thus our data suggest that biomedical factors appear to confer the greatest risk of major impairments; sociodemographic factors appear to have a significant impact on educational risk in extremely premature infants who do not die. Continued follow-up with biomedical and developmental-social interventions appears warranted to decrease the risk of educational underachievement in this population. PMID- 1919895 TI - Introduction of intravenous lipid administration on the first day of life in the very low birth weight neonate. AB - OBJECTIVE: To investigate lipid tolerance in sick, ventilator-dependent, very low birth weight infants from the first day of life and the effects of early introduction of intravenously administered lipid (IVL) on glucose homeostasis. METHOD: Twenty-nine infants in the neonatal intensive care unit with birth weight less than 1500 gm received isocaloric, isonitrogenous parenteral feedings from day 1 with either IVL, 1 gm/kg from day 1 to 3 gm/kg from day 4 (group I; n = 16), or IVL added only from day 8 (group II; n = 13). Possible adverse clinical effects were monitored. Blood metabolites, nonesterified fatty acids, serum triglycerides, and insulin levels were determined daily. Arterial blood gases were measured and changes in partial pressures of oxygen and of carbon dioxide in arterial blood were compared between the two groups. RESULTS: Early lipid infusion did not appear to have deleterious effects on blood gas tensions or to increase respiratory morbidity. The incidence of other adverse clinical effects that may be associated with IVL was not increased by earlier introduction of lipid. Serum lipid values were comparable to those of preterm infants receiving IVL at a later postnatal age. Blood glucose concentrations were higher in group II (mean, 7.50 (SEM 0.43) mmol/L) than in group I (mean, 6.01 (SEM 0.28) mmol/L; p less than 0.05). There was no evidence of increased gluconeogenesis in infants in group I and no correlation between blood glucose concentrations and serum nonesterified fatty acid concentrations. CONCLUSION: When given infusion rates not exceeding 0.15 gm/kg/hr, sick, very low birth weight infants can tolerate IVL with stepwise dose increases from the first day of life without an increased incidence of possible adverse effects. PMID- 1919896 TI - Prophylactic intravenous administration of immune globulin in preterm infants: effect on serum immunoglobulin concentrations during the first year of life. AB - In a prospective study, serum IgG, IgA, IgM, and IgG subclass levels of 66 preterm infants (gestational age less than or equal to 34 weeks) were measured sequentially from birth to 12 months of life. Infants were divided into two groups, comparable for gestational age, birth weight, sex, and intensive care, on the basis of admission order: the treatment group, consisting of 33 infants who received intravenous immune globulin therapy (0.5 gm/kg at 10-day intervals) prophylactically, and the control group, consisting of 33 infants who did not receive. Twenty of the 33 treated infants received only one infusion and the remaining 13 received two to five infusions. The mean number of infusions per neonate was 1.96. Immunoglobulin measurements showed that the proportion of infants with an IgG level of greater than or equal to 7 gm/L on the tenth and thirtieth days of life was significantly higher in the treatment than in the control group (p less than 0.01). At the same ages, mean serum IgG, IgG1, and IgG2 concentrations were significantly higher in the treatment group (p less than 0.001). Thereafter levels in both groups fell progressively, reaching their lowest point between 3 and 5 months of age. During this period, profound hypogammaglobulinemia (IgG less than 2 gm/L) was observed in 3 of 33 treated and 11 of 33 untreated infants (p less than 0.05). By 3 months of age, mean serum total IgG concentrations were still significantly higher in treated than in untreated infants (p less than 0.05), but the IgG subclass concentrations were not. After the third month, no significant differences between the two groups were observed. Moreover, the sequentially measured serum IgA and IgM levels in the two groups remained comparable from birth to age 12 months. The IgG level at different ages from 3 to 12 months was not correlated with either birth weight or the number of infusions performed during the neonatal period (p greater than 0.1). We conclude that prophylactic intravenous administration of immune globulin to preterm infants with a birth weight of 1000 to 2000 gm, at a dose of 0.5 gm/kg every 10 days, results in maintenance of a satisfactory serum IgG level throughout the high-risk period for infections. Such treatment does not have a suppressive effect on subsequent serum immunoglobulin concentrations. PMID- 1919897 TI - Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates. National Institute of Child Health and Human Development Neonatal Research Network. AB - We studied the occurrence of necrotizing enterocolitis in 2681 very low birth weight infants during an 18-month period to characterize the biodemographic and clinical correlates. Proven necrotizing enterocolitis (Bell stage II and beyond) occurred in 10.1% of study infants; necrotizing enterocolitis was suspected in 17.2% of study infants. Positivity of blood cultures was related to necrotizing enterocolitis staging. The mortality rate increased only for stage III necrotizing enterocolitis (54% died). Logistic regression identified medical center of birth, race, gender, birth weight, maternal hemorrhage, duration of ruptured membranes, and cesarean section as significant risk factors. For one center the odds ratio was 3.7, whereas for another center it was only 0.3. For black boys, the odds ratio was 2.3 relative to nonblack boys; for girls, race did not affect prevalence of necrotizing enterocolitis. Age at onset was related to birth weight and gestational age. Intercenter differences in necrotizing enterocolitis prevalence were related to time required to regain birth weight and other indicators of fluid management. Gram-positive organisms predominated in positive blood cultures for stage I and II necrotizing enterocolitis; enteric bacteria were isolated more frequently in infants with stage III disease. We conclude that necrotizing enterocolitis prevalence varies greatly among centers; this may be related to early clinical practices of neonatal care. PMID- 1919898 TI - Changes in the pharmacodynamic response to fentanyl in neonates during continuous infusion. AB - Tolerance to opioid-induced sedation has been reported in neonates sedated with fentanyl by continuous infusion while undergoing extracorporeal membrane oxygenation. We undertook a prospective analysis of eight newborn infants sedated with fentanyl during extracorporeal membrane oxygenation therapy for respiratory failure. We recorded daily mean fentanyl infusion rate, measured serial plasma fentanyl concentrations, and documented the occurrence of spontaneous motor activity or respiratory effort. Mean fentanyl infusion rate increased steadily during the period of infusion from a mean of 9.2 +/- 1.9 (SEM) micrograms/kg per hour on day 1 to a mean of 21.9 +/- 4.5 micrograms/kg per hour by day 6. Mean plasma fentanyl concentrations increased steadily during the period of fentanyl infusion from 3.1 +/- 1.1 (SEM) ng/ml on day 1 to 13.9 +/- 3.2 ng/ml on day 6. All infants exhibited movement in response to gentle tactile stimulation throughout the period of infusion, and seven of eight infants manifested spontaneous movement of the extremities and eye opening. Our results indicate that when fentanyl is used for sedation in neonates, the plasma concentrations required for satisfactory sedation steadily escalate, possibly indicating the rapid development of tolerance to the sedating effects of fentanyl. PMID- 1919899 TI - Reversible neurologic abnormalities associated with prolonged intravenous midazolam and fentanyl administration. AB - An encephalopathy developed in three infants in the intensive care unit after heavy sedation with midazolam and fentanyl for 4 to 11 days. The affected infants had poor social interaction, decreased visual attentiveness, dystonic postures, and choreoathetosis. Symptoms cleared completely in 5 days to 4 weeks. Retrospective review of records of all children treated in the intensive care unit with prolonged intravenous administration of midazolam revealed that 45 children could be assessed neurologically on withdrawal of sedation. Three children had definite and two had possible neurologic sequelae (5/45, 11.1%). All had received concomitant intravenous fentanyl therapy. Neurologic sequelae were significantly associated with young age, female gender, low serum albumin concentration, and concomitant administration of aminophylline. This encephalopathy may represent a benzodiazepine withdrawal syndrome, a prolonged agonist action on the benzodiazepine receptor, or the combined effects of multiple toxic, metabolic, and infectious insults to the central nervous system of infants in the intensive care unit. Prolonged use of intravenous midazolam sedation necessitates careful dosing, monitoring, and discontinuation, particularly in infants and young children. PMID- 1919900 TI - Movement disorder after withdrawal of fentanyl infusion. PMID- 1919901 TI - Duration of serum anticapsular antibody after a two-dose regimen of a Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine and anamnestic response after a third dose. PMID- 1919902 TI - Antibody persistence four years after primary immunization of infants and toddlers with Haemophilus influenzae type b CRM197 conjugate vaccine. PMID- 1919903 TI - 25-Hydroxyvitamin D therapy in children with active juvenile rheumatoid arthritis: short-term effects on serum osteocalcin levels and bone mineral density. PMID- 1919904 TI - Congenital heart disease, parental stress, and infant-mother relationships. AB - The effect of congenital heart disease on early social relationships was assessed by observing 42 infants with the disease and 46 healthy infants in a standardized laboratory setting with their mothers. Significantly fewer infants with congenital heart disease, in comparison with healthy peers, were considered to have secure relationships with their mothers. The quality of the infant-mother relationship in the group with congenital heart disease was not related to parents' reports of their own stress or psychologic well-being. Severity of illness did not have a direct effect on the quality of the infant-mother relationship, but securely attached infants showed more subsequent improvement in health than insecurely attached peers showed. Attention to the infant-mother relationship in clinical care may improve the social development of babies with congenital heart disease and may have positive effects on physical health as well. PMID- 1919905 TI - Neurobehavioral sequelae of fetal cocaine exposure. AB - The number of infants born to cocaine-using mothers has continued to rise during the past 5 years. Maternal cocaine use during pregnancy is associated with medical and life-style characteristics detrimental to fetal and infant development. Cocaine exposure has been independently linked to growth retardation and impaired fetal oxygenation even when polydrug use and other confounding factors are considered. Neurologic and neurobehavioral abnormalities noted in the immediate neonatal period have also been associated with fetal cocaine exposure. The direct and indirect toxic effects of cocaine, per se, have not yet been independently linked to specific behavioral outcomes because of small sample sizes, confounding factors, and lack of long-term follow-up. The impoverished environments and increased risk for out-of-family placement of cocaine-exposed infants are known independent correlates of negative developmental outcomes. Poor maternal nutrition, lack of prenatal care, and other health and life-style factors related to maternal cocaine use during pregnancy also appear to be factors mediating the developmental problems of cocaine-exposed infants. The cocaine-using mother often uses other drugs, particularly alcohol, independently known to be linked to growth and behavioral impairments similar to those proposed for cocaine-exposed infants. Accounting for these multiple confounding variables in studies of the specific effects of cocaine on neurobehavioral outcome may be scientifically appropriate, but in clinical practice these factors cannot be "isolated," and their statistical consideration in studies does not diminish clinical risk. Finally, currently available studies of behavioral outcome have restricted their samples to term infants. It is possible that preterm infants may be less affected by prenatal cocaine exposure because of decreased exposure. However, because epidemiologic studies suggest that prematurity is a sequelae of maternal cocaine use, restriction of samples to term or appropriately sized infants may underestimate the spectrum of morbidity associated with cocaine exposure. We believe that maternal cocaine use during pregnancy is a "marker" variable for early impairments in infant growth and behavioral functioning that have long-term implications for later developmental outcome, especially for learning disabilities and behavioral disorders. Critically assessing the independent contribution of cocaine to negative developmental outcome and determining whether early neonatal abnormalities are permanent or modifiable may allow clinical intervention and improved social policy. Assessing the independent effects of cocaine on child developmental outcome will require carefully designed, long-term, longitudinal, population-based studies with samples large enough to allow multivariate data analyses and statistical control of confounding medical and social variables. PMID- 1919906 TI - Female infant affected with an X-linked disease. PMID- 1919907 TI - Infantile bilateral striatal necrosis. PMID- 1919908 TI - High doses of methylprednisolone for Kasabach-Merritt syndrome. PMID- 1919909 TI - Magnesium metabolism in diabetes mellitus. PMID- 1919910 TI - Fine structure and sugar transport functions of the tegument in Clinostomum marginatum (Digenea: Clinostomatidae): environmental effects on the adult phenotype. AB - Digenean flukes can be classified into 3 groups according to their location in the host: the lumen of the alimentary canal or associated organ, body cavity or tissue, and external surfaces. We obtained adults of Clinostomum marginatum that had matured in these 3 habitats and compared the fine structure and glucose transporting capacity of their teguments. Adults from the esophagus of herons, Ardea herodias, had thick, smooth teguments and took up glucose by facilitated diffusion, the type of transport that is Na(+)-independent and insensitive to phlorizin. By contrast, the surfaces of adults cultured from metacercariae in body cavities of laboratory mice were amplified 3-5-fold due to numerous irregular projections of the tegument. Glucose transport by these worms was largely Na(+)-dependent and inhibited by phlorizin, indicating active transport. Ectoparasites from herons' mouths had relatively thick, smooth teguments, but these worms always were encrusted with bacteria and yeast that are known to absorb and metabolize glucose. Most of the attached bacteria, and the apparent glucose uptake associated with their presence, were removed by treating the worms with antibiotics prior to transport assays. As facilitated diffusion and active transport are operational simultaneously in metacercariae, the type of transport function, if any, expressed in the adult is determined by environmental conditions associated with the worm's habitat. PMID- 1919911 TI - Lockenloia sanguinis n. gen., n. sp. (Nematoda: Dracunculoidea) from the heart of a nurse shark, Ginglymostoma cirratum, in Florida. AB - Lockenloia sanguinis n. gen., n. sp. (Nematoda: Dracunculoidea) is described from fragments collected in the atrium of the heart of a male nurse shark, Ginglymostoma cirratum (Bonnaterre). The new genus is distinguished by its reduced buccal capsule; body that expands abruptly just behind the cephalic extremity; long and undivided esophagus; and subconical, pointed tail. Until the systematics of the superfamily are revised, the familial placement of the taxon is unclear. PMID- 1919912 TI - Antigenic characterization of Psoroptes spp. (Acari: Psoroptidae) mites from different hosts. AB - Immunoblotting with defined antigens and antisera revealed extensive and nearly complete antigenic cross-reactivity between Psoroptes spp. mites from a bighorn sheep, a mule deer, a cow, and a rabbit. Antigenic differences were not detected between mites from the sympatric bighorn sheep and mule deer. However, minor antigenic differences between mites from the cow and rabbit suggested that these mites were distinct from each other, as well as from the mites from the bighorn sheep and mule deer. These results are consistent with earlier morphologic studies of these populations of mites and provide additional support for the hypothesis that putative populations and/or species of Psoroptes mites may not be reproductively or ecologically isolated, particularly when their hosts are sympatric. PMID- 1919913 TI - Monoclonal antibodies that react with Leishmania (Viannia) naiffi. AB - Monoclonal antibodies were raised against Leishmania (Viannia) naiffi, which recently has been characterized as a new species. BALB/c mice were immunized with membrane-enriched fractions of a mixture of L. (V.) naiffi isolates. Subsequent fusion of immunized splenocytes with NS-1 myeloma cells resulted in the production of 5 Mabs (N1-N5). Screening by ELISA and indirect immunofluorescence against an extensive cross-panel of Leishmania strains revealed that N3 was species-specific and could thus be used to identify L. (V.) naiffi. N2 and N5 reacted only with strains of L. (V.) naiffi and Leishmania (Viannia) braziliensis, and therefore could be used in conjunction with N3 to identify L. (V.) braziliensis parasites. These species-specific Mabs will therefore be useful additions to the panel of antibodies already available for the identification of Leishmania species. N1 and N4 were found to recognize a small, glycosylated molecule present on all L. (V.) naiffi and L. (V.) braziliensis isolates that is related to the GIPL family of membrane glycophospholipids previously described for Leishmania (Leishmania) major. PMID- 1919914 TI - Infectivity of cryopreserved Giardia cysts for Mongolian gerbils (Meriones unguiculatus). AB - Although Giardia species trophozoites have been cryopreserved successfully, no report on the successful cryopreservation of cysts could be found. Using infectivity to Mongolian gerbils (Meriones unguiculatus) as a measure of cyst viability, we tested the viability of 4 strains of Giardia cysts that had been cryopreserved for 1-67 wk. Cysts were frozen in either Keister's medium or physiological saline, both containing 5% or 7.5% dimethylsulfoxide as the cryoprotectant. Viability of cryopreserved cysts was dependent upon the number of cysts inoculated, the length of time cysts were held at 4 C before cryopreservation, and the cryopreserving medium. Infection was established in gerbils by inoculating them with cysts that had been cryopreserved for up to 67 wk, cysts that had been held for less than 30 days before cryopreservation, and cysts frozen in Keister's medium. Saline appears to be unsuitable as a freezing medium for the cryopreservation of Giardia cysts. PMID- 1919915 TI - Kinetic ELISA for detection of antibodies to Psoroptes sp. (Acari: Psoroptidae) in bighorn sheep (Ovis canadensis). AB - A kinetic enzyme-linked immunosorbent assay (ELISA) was developed using antigenic extracts prepared from Psoroptes cuniculi mites and sera from 37 Psoroptes sp. infested and 43 uninfested bighorn sheep (Ovis canadensis). Serial dilutions of these serum samples, representing 3 bighorn sheep subspecies and 9 geographic areas, gave parallel responses when plotted as log dilution versus log kinetic rate. Therefore, all 80 samples were run at a single dilution (1:100) and positive/negative cutoff values were established as the mean kinetic rate of all negative sera plus either 2, 3, or 4 standard deviations. The resulting ELISA was highly reproducible and accurate with sensitivities and specificities of 100% and 97.7%, 94.6% and 97.7%, and 94.6% and 100%, respectively. This immunoassay will be useful for prospective and retrospective studies assessing the distribution and prevalence of Psoroptes sp. infestations in bighorn sheep. PMID- 1919916 TI - The niche of Salsuginus thalkeni, a gill parasite of Fundulus zebrinus. AB - Distribution of a monogenean parasitic helminth Salsuginus thalkeni on the gills of the fish Fundulus zebrinus is described by calculation of mean positions and niche breadths on the linear spatial resource gradients gill filament length, gill arch length and arch number. All distributions are given for parasites in the presence and absence of various combinations of potential competitors, namely the 6 other parasite species that occupy the same host species. Filament niche breadth was narrowest in the absence of potential competitors; breadth on arch was widest in the presence of potential competitors. Breadth on both resources was correlated positively with mean number of parasites per individual. Arch breadth exhibited cyclic seasonal changes, being lowest in early to mid-summer. Mean position exhibited no repeated pattern of variation on either resource. The results are considered consistent with predictions about the niche structures of species in unsaturated noninteractive specialist communities. PMID- 1919917 TI - Manifestations of immunity in sheep repeatedly infested with Amblyomma americanum ticks. AB - Three sheep were infested 4 times with 100 Amblyomma americanum tick pairs and kept indoors until the natural termination of the infestations. Characteristics of the tick populations that show efficiency of feeding, fertility, and offspring development, and ELISA antibodies to tick salivary gland extracts were studied at each infestation. On average, female ticks fed on tick-naive sheep detached at 12.1 +/- 0.2 (mean +/- standard error) days, weighed 492 +/- 16.8 mg, engorged 40.7 mg per day, and 35% survived to detachment during the first infestation. During the fourth infestation, they detached at 17.3 +/- 0.8 days, weighed 321 +/ 14.4 mg, engorged 18.8 mg per day on average, and 23% survived to detachment. On average, oviposition of female ticks fed on tick-naive sheep started at 11.8 +/- 0.6 days of detachment, the egg mass weighed 236 +/- 13.2 mg, 43% of the female weight turned into eggs, and 89% of the ticks that detached survived to oviposition during the first infestation. During the fourth infestation, oviposition started at 15.1 +/- 0.5 days, the eggs weighed 103 +/- 9.9 mg, 13% of the tick weight became eggs, and 67% of the ticks survived to oviposition. On average, eclosion started at 35.4 +/- 0.9 days of oviposition and 83% of the egg batches hatched in the first infestation. During the fourth infestation, eclosion started on day 34.9 +/- 0.7, and 47% of the egg batches hatched. Anti-tick resistance was expressed as an inhibition of feeding, fertility, and offspring development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919918 TI - Antigens of Amblyomma americanum ticks recognized by repeatedly infested sheep. AB - Sera were taken from 3 sheep that had been infested 5 times with Amblyomma americanum and that exhibited manifestations of humoral depression to homologous antigens and anti-tick resistance. Proteins extracted from the intestine or salivary glands of unfed ticks or salivary glands from partially (3-day) fed ticks were analyzed by polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-PAGE. Antigens recognized by the sheep in the same materials before and after each infestation were analyzed by western blots. The sheep responded to 44 antigens. Nine to 23 antigens were recognized by the preinfestation sera and the sera of 2 gnotobiotic sheep. Four antigens (34,000, 36,500, 38,000, and 115,000 MW) were revealed conspicuously by the serum of the first infestation but very weakly or not at all by the sera of the third infestation onward. Two antigens (35,500 and 29,000 MW) from fed salivary glands were revealed only by sera taken after manifestations of resistance had appeared. These antigens may be responsible for anti-tick protection. The 29,900 MW antigen was present also in salivary extracts of Boophilus microplus. PMID- 1919919 TI - Qualitative characterization of antibody responses to single and multiple Brugia pahangi infections in jirds. AB - Antibody responses of jirds, singly and multiply inoculated with Brugia pahangi infective larvae (L3), to soluble somatic extracts of adult parasites were characterized by western blot analysis. Forty-two protein bands ranging in molecular weight from 12 to 160 kDa were recognized by sera from infected jirds. Antibody recognition of individual B. pahangi antigen bands in this assay appears to be independent of antibody enzyme-linked immunosorbent assay (ELISA) titers to crude parasite extract, severity of lymphatic lesions, levels of microfilaremia, numbers of L3 inoculated, or numbers of adult parasites in individual jirds. Antibody recognition of protein bands with molecular weights of 37 kDa, 21 kDa, and 17 kDa, however, did temporally correspond with certain parasitological and pathologic events. Antibody against the 37-kDa protein band first was identified at the onset of patency, reaching a 90% prevalence rate by 90 days postinfection (DPI). The prevalence of this antibody remained high. Antibody recognition of the 21-kDa protein band first occurred at 90 DPI and gradually increased in prevalence during the course of infection temporally similar to the increase in microfilaremia. Recognition of the 17-kDa protein band first occurred at 48 DPI, reached a maximum prevalence of 80% at 90 DPI, and decreased to a minimal prevalence by 160 DPI. Prevalence of antibody responses to the 17-kDa protein band corresponded temporally with the kinetics of the rise and fall of numbers of intralymphatic thrombi. The patterns of antibody response to these 3 bands were similar in both singly and multiply inoculated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919920 TI - Separation of antigens from Sarcocystis species using chromatofocusing. AB - Crude antigen preparations from bradyzoites of Sarcocystis species exhibit a high degree of cross-reactivity with antisera against heterologous Sarcocystis species, preventing the development of a species-specific immunological test for sarcocystiosis. In this study, we fractionated bradyzoite-derived protein extracts from Sarcocystis tenella, Sarcocystis arieticanis, Sarcocystis gigantea, and Sarcocystis muris by chromatofocusing and obtained distinct protein elution profiles for each species. We then examined the isolated protein fractions for antigenicity with homologous and heterologous reference sera in an enzyme-linked immunosorbent assay. Whereas some antigenic fractions of bradyzoite proteins had equally high reactivity with the homologous and heterologous sera, the reactivity of other fractions was 3-38 times higher with homologous serum than with heterologous sera. Mice immunized with less cross-reactive protein fractions of S. gigantea and S. muris bradyzoites produced a specific immune serum. Thus, it is possible to isolate species-specific antigens from crude mixtures of bradyzoite-derived Sarcocystis antigens for development of species-specific immunological tests for sarcocystiosis. PMID- 1919921 TI - Antibody responses and protective immunity in rats receiving repeated inoculations of Strongyloides ratti. AB - The relationship between specific antibody responses and protective immunity against Strongyloides ratti was examined in rats receiving 10, 50, or 500 infective larvae (L3) at weekly intervals. No specific IgG response was detected in rats receiving 10-L3 inoculations for 7 wk. Fifty- and 500-L3 inoculations induced an IgG response by weeks 2 and 3, respectively, and a higher IgG response was induced in rats receiving the higher doses. All 3 inoculation doses induced high IgE responses, but the kinetics were different. IgE in the 10-L3 group continued to rise from weeks 4 to 7. In the 50- and 500-L3 groups, IgE was detected first at week 3 and increased until week 5. It then declined in the 500 L3 group and the titer at week 7 was significantly lower than that at week 5, whereas it remained the same in the 50-L3 group. The number of larvae recovered from the head 40 hr after a challenge inoculation (1,000 L3) significantly declined by weeks 7, 3, and 2 in rats receiving 10, 50-, and 500-L3 inoculations, respectively. Intestinal worm burdens increased for 7 wk in the 10-L3 group, 5 wk for the 50-L3 group, and 2 wk for the 500-L3 group. These findings indicate that repeated inoculations of low doses of L3 induce delayed and limited protective immunity to a heavy challenge and worm expulsion from the intestine. There was a temporal correlation between the levels of protection and serum IgG, whereas circulating IgE level did not seem to affect directly either the level of the resistance or expulsion of intestinal worms. PMID- 1919922 TI - Lectin-binding properties of the surfaces of in vitro-transformed Schistosoma mansoni and Echinostoma paraensei sporocysts. AB - As carbohydrates on the surfaces of sporocysts of digenetic trematodes may be targets of attack by the molluscan internal defense system, the lectin-binding patterns of living, in vitro-transformed sporocysts of Schistosoma mansoni and Echinostoma paraensei were characterized. Schistosoma mansoni sporocysts specifically bound 8 and E. paraensei 6 of 11 lectins examined. Sporocysts of the 2 species responded differently to 7 of the 11 lectins. Lectins inhibitable by mannose, galactose, and N-acetylgalactosamine were bound by both species. Lectins inhibited by fucose and N-acetylglucosamine bound uniquely to S. mansoni, and an N-acetylneuraminic acid (NeuNAc)-inhibitable lectin bound only to E. paraensei. Preincubation of sporocysts of either species in the plasma of the host snail Biomphalaria glabrata for as long as 24 hr only marginally altered the subsequent binding of lectins. Pretreatment of S. mansoni sporocysts with pronase E and trypsin substantially altered subsequent lectin binding, but similar treatment of E. paraensei sporocysts had little effect. A neuraminidase enzyme derived from Clostridium perfringens diminished binding of the NeuNAc-inhibitable lectin to E. paraensei sporocysts. This study indicates that lectin-binding monosaccharides are expressed abundantly on sporocyst surfaces, they vary considerably between 2 species parasitizing the same host, and they are not obscured readily or altered by exposure to host plasma. PMID- 1919923 TI - Transplantation into jirds as a method of assessing the viability and reproductive integrity of adult Acanthocheilonema viteae from culture. AB - The reproductive integrity and viability of adult female Acanthocheilonema viteae (syn. Dipetalonema viteae) maintained in culture for relatively long periods were assessed by transplantation into jirds. Worms cultured in chemically defined NI medium for approximately 3-4 wk remained active, but microfilarial release declined to barely detectable levels. Microfilarial production, however, was restored when the worms were transplanted subcutaneously into jirds. When cultured in NI medium beyond 4 wk no restoration of microfilarial production occurred on transplantation, presumably due to irreversible injury to the reproductive system. However, when NI medium was supplemented with fetal bovine serum resumption of microfilarial production occurred in transplanted females that had been in culture for as long as 2 1/2 mo. The addition of serum to NI medium played an important role in maintaining and protecting the functional integrity of the reproductive system. PMID- 1919924 TI - Effects of route of inoculation on the site of development of Caryospora bigenetica (Apicomplexa: Eimeriidae). AB - The sites of infection by Caryospora bigenetica in Swiss-Webster mice (Mus musculus) were demonstrated after 7 routes of inoculation: oral, intraperitoneal, intravenous, intramuscular, subcutaneous, dermal, and intraocular. All mice exhibited clinical signs of dermal coccidiosis 9 days after inoculation regardless of the inoculation route. Signs included swelling of the facial tissue, footpads, and scrota (male mice). Developmental stages of the parasite were found in the muzzle, tongue, footpad, lumbar subcutaneous tissue, biceps femoris muscle, conjunctiva, and eye; the latter 3 sites represent new sites of development. The site of development of the parasite in the host tissue was independent of experimental inoculation route. PMID- 1919926 TI - Metastatic capability of Leishmania (Viannia) panamensis and Leishmania (Viannia) guyanensis in golden hamsters. AB - The pattern and kinetics of internal dissemination and frequency of cutaneous metastatic lesions resulting from experimental infection of golden hamsters with Leishmania (Viannia) panamensis and Leishmania (Viannia) guyanensis were examined. Nineteen strains were evaluated: 16 L. (V.) panamensis isolated from patients and 3 L. (V.) guyanensis, 2 isolated from human cases and 1 WHO reference strain originating from a sandfly vector. Lymphatic dissemination occurred within 3 mo and was observed for 16 of 16 (100%) of L. (V.) panamensis and 3 of 3 (100%) of L. (V.) guyanensis. Parasites were cultured infrequently from liver and spleen: 3 of 125 (2%) L. (V.) panamensis and 1 of 22 (5%) L. (V.) guyanensis. Decreased frequency of isolation from the inoculation site and draining lymph nodes over time was accompanied by increased frequency of isolation from distant lymph nodes. Dilution of triturated tissue samples resulted in an increased efficiency of parasite culture. Both primary lesions and secondary cutaneous metastatic lesions were more severe in hamsters infected with L. (V.) guyanensis than with L. (V.) panamensis. Cutaneous metastatic lesions were produced more frequently by L. (V.) guyanensis, 24 of 46 hamsters (52%), than by L. (V.) panamensis, 28 of 252 hamsters (11%). Individual Leishmania strains displayed distinctive propensities to produce cutaneous metastases, manifested as a reproducible phenotype. Metastatic pathogenicity was independent of the inoculum dose, supporting the dissociation of infectivity and pathogenicity. PMID- 1919925 TI - Plasmodium berghei ookinete densities in three anopheline species. AB - Plasmodium berghei ookinete kinetics and densities were examined in the blood meals of 3 species of Anopheles mosquitoes fed simultaneously from a gametocytemic mouse. Simple techniques were developed for estimating relative and absolute ookinete densities within individual mosquito blood meals. The kinetics of ookinete formation were similar in all 3 species, with peak ookinete densities occurring from 12 to 24 hr postingestion. Ookinete densities consistently were lower in Anopheles stephensi than in Anopheles albimanus or Anopheles freeborni and could not be accounted for by species differences in blood meal volumes or gametocyte densities. Likely explanations involve species differences in blood meal hemolysis or sampling error as the result of ookinete emigration from the blood meal. PMID- 1919927 TI - Anthelmintic-induced destrobilation and its influence on calculated drug efficacy in Hymenolepis diminuta infections in rats. AB - Anthelmintic efficacy studies typically involve direct counts of worms remaining in the host shortly after drug treatment. Few such studies, however, have considered the phenomenon of tapeworm destrobilation when determining effective dosages. The present study reports on the frequency of drug-induced destrobilation and the subsequent regeneration of Hymenolepis diminuta in rats following treatment with niclosamide or praziquantel and its implications with respect to the apparent efficacy of these anthelmintics. Drug efficacies very similar to those reported in the literature were determined upon examination of infected animals 24 hr posttreatment. Small regenerating worms were, however, observed in the small intestine of rats 8 days after treatment, indicating that destrobilated worms were present, but overlooked, during the initial examination. Within several days posttreatment, destrobilated worms can regenerate to a size that is readily apparent in the gut contents, allowing the effective dosage to be determined with much greater confidence. Due to the demonstrated ability of these destrobilated worms to regenerate to the gravid state, it is imperative that a fully effective anthelmintic dosage be determined and administered. PMID- 1919928 TI - In vitro activity of the human neutrophil cathepsin G on Eimeria tenella sporozoites. AB - The role of human neutrophil cathepsin G (Cat G) on Eimeria tenella sporozoites was studied in vitro. Sporozoites were incubated for 2 hr at 37 C in PO4 buffer, 0.9% NaCl (PBS), pH 7.6 in the presence of Cat G (50 micrograms/ml), diisopropyl fluorophosphate-inhibited Cat G (DFP-Cat G) (50 micrograms/ml) or PBS alone, prior to being inoculated into embryonated eggs. As judged by oocyst production on day 7 postinoculation, embryo mortality and the hemorrhage scores, both Cat G and DFP-Cat G demonstrated anticoccidial activity; greater activity was obtained with the DFP-Cat G. Sporozoites were exposed also to increasing concentrations of native and trypsin-digested DFP-Cat G (0-100 micrograms/ml) under the same conditions. Significant protection (37% and 49% for native and digested DFP-Cat G, respectively) was obtained with a low concentration (5 mu/ml), and higher concentrations resulted in 70% and 84% protection, respectively. The primary bactericidal domain of Cat G, the HPQYNQR peptide, at 3 concentrations (25, 50, and 100 micrograms/ml), reduced the oocyst production by 46%, 16%, and 15%, respectively. The anticoccidial activity of Cat G may involve a peptide fragment different from the antimicrobial domain of the enzyme. PMID- 1919929 TI - Development of Leishmania (Viannia) panamensis lesions and relationship of numbers of amastigotes to lesion area on antimony-treated and untreated hamsters. AB - Young adult (60-70-g) male golden hamsters (Mesocricetus auratus) each were injected intradermally at the dorsal base of the tail with 15 x 10(6) promastigotes of Leishmania (Viannia) panamensis (MHOM/PA/83/WR539), and progression and regression of subsequent lesions were evaluated for up to 17 wk postinfection (PI) as to area, weight, and number of amastigotes within lesions in untreated hamsters and in hamsters treated with meglumine antimoniate (Glucantime). In untreated hamsters total area of lesion, weight, and numbers of amastigotes generally increased rapidly and concomitantly up to 3-4 wk PI. Amastigote numbers tended to decrease from 4 to 11 wk PI and subsequently the numbers of amastigotes within the lesions decreased rapidly, whereas relatively little change occurred in the area and weight of the lesions. Meglumine antimoniate treatment of cutaneous hamster lesions resulted in marked concomitant decrease in size of the lesions and numbers of amastigotes within the lesions examined 1 wk after treatment. Measurement of the area of cutaneous leishmanial lesions thus would appear to be a valid method of evaluating the efficacy of promising compounds against L. panamensis in hamsters when measurements are taken 3-5 wk after experimental infection and reflects the number of amastigotes present in the lesion. PMID- 1919930 TI - Bacteria associated with tegument of Clinostomum marginatum (Digenea). AB - Adults of Clinostomum marginatum freshly collected from a heron, Ardea herodias, were examined using transmission electron microscopy. Specimens from the mouth of the bird were encrusted with bacteria that were not removed by washing unless the saline contained antibiotics. There was no evidence that the attached bacteria were damaging to the trematode tegument. Three species of Gram-negative bacteria were isolated from the worm surfaces and identified; Achromobacter sp. was present in pure culture on 4 of 6 original cultures and in mixed culture with Edwardsiella tarda and Enterobacter agglomerans in 2 cultures. These species and 3 unidentified species of bacteria were isolated from the oral epithelium of the heron. Microorganisms were not seen attached to the surfaces of worms recovered from the esophagus. Because E. tarda and E. agglomerans were the only species isolated from the heron esophagus, the intimate bacterial-worm association in the heron mouth may be due specifically to Achromobacter sp. PMID- 1919931 TI - Helminth parasites of the western sandpiper, Calidris mauri (Aves), from El Paso and Hudspeth counties, Texas. AB - Fifty western sandpipers, Calidris mauri, from El Paso and Hudspeth counties, Texas, were collected and examined for helminth parasites. Fifty-three helminths (means abundance = 1.06, SD = 2.31) consisting of 4 cestode and 1 nematode species were collected. The helminth community showed low species richness (5), low diversity and evenness (0.05, 0.14), low concentration for dominance (0.19), and all species were contagiously distributed. There were no clearly identifiable core species. PMID- 1919932 TI - In vitro cultivation of Sarcocystis neurona from the spinal cord of a horse with equine protozoal myelitis. AB - Asexual stages of Sarcocystis neurona were seen in cultured bovine monocytes (M617) inoculated with tissue homogenates from the spinal cord of a horse with naturally acquired protozoal myelitis. Organisms first were observed as intracytoplasmic schizonts and later as motile extracellular zoites capable of infecting surrounding M617 cells. Parasites most often occurred as clusters of merozoites dispersed throughout the host cell cytoplasm; however, schizonts also contained merozoites arranged in a radial fashion surrounding a prominent residual body. Schizonts divided by endopolygeny. The parasite has been maintained beyond 280 days in the laboratory by serial passage of infected M617 cells. PMID- 1919933 TI - Toxoplasma gondii-like schizonts in the tracheal epithelium of a cat. AB - Toxoplasma gondii-like schizonts were found in tracheal epithelium of an 8-yr-old male cat. The parasites were located in parasitophorous vacuoles within the host cell cytoplasm, divided by schizogony, contained periodic acid-Schiff-positive granules, and reacted with anti-T. gondii serum but not with anti-Neospora caninum serum. Mature schizonts were 7.0 x 5.9 microns (5-10 x 4-10 microns; n = 22) and contained 4-16 merozoites. The merozoites were approximately 5 x 1 microns. PMID- 1919934 TI - A Brugia species infecting rabbits in the northeastern United States. AB - Brugia sp. microfilariae were observed in more than 60% of wild rabbits collected on Nantucket Island, Massachusetts. The microfilariae measured 294-344 microns in length and had the characteristic subterminal and terminal nuclei observed in other Brugia microfilariae. The microfilaria is similar to those described for Brugia leporis in rabbits in Louisiana. This may be the Brugia species responsible for 21 documented cases of human infection in the northeastern United States. PMID- 1919935 TI - Influence of the nontarget mollusc Marisa cornuarietis on the hourly cercarial production of Schistosoma mansoni from Biomphalaria glabrata. AB - A comparative study of hourly cercarial productivities of Schistosoma mansoni from infected Biomphalaria glabrata was carried out in the presence of either healthy B. glabrata (control) or healthy Marisa cornuarietis (experimental). The results showed that, with M. cornuarietis, almost all the hourly cercarial productivities increased by a factor varying from 1.3 to 2.5 without modification of the shedding period. PMID- 1919936 TI - Serological survey for heartworm (Dirofilaria immitis) in dogs in Washington. AB - The serologic prevalence of Dirofilaria immitis infection in 601 dogs in Washington was investigated in 1989-1990. Blood samples for serum were obtained from dogs approximately 2 yr of age or older in humane society shelters (n = 392) or veterinary clinics (n = 209). Serum samples were tested for heartworm infection using an enzyme-linked immunosorbent assay antigen test. Three (0.5%) dogs were positive for D. immitis infection, all of which were born and lived several years in states other than Washington. Heartworms have not been detected during the last 9 yr in the 1,203 dogs examined at the Washington Animal Disease Diagnostic Laboratory, Pullman, Washington. Consequently, the likelihood of indigenous heartworm infections in dogs in Washington remains low at this time. PMID- 1919937 TI - Echinococcus multilocularis--a model for imaging research. AB - Magnetic resonance images of transverse, sagittal, and coronal sections of Meriones unguiculatus abdomens experimentally infected with Echinococcus multilocularis revealed alveolar cyst masses that were especially prominent in the late phase of infection. PMID- 1919938 TI - Evidence for host allozymes present on electrophoretic gels of trematode parasites (Digenea: Plagiorchiiformes). AB - An allozyme analysis of trematode species Glypthelmins californiensis, Glypthelmins quieta, Glypthelmins pennsylvaniensis, Glypthelmins hyloreus, and Haplometrana intestinalis from hosts Rana aurora, Rana clamitans, Hyla crucifer, Pseudacris triseriata, and Rana pretiosa, using starch gel electrophoresis, revealed allozymes for glucose-phosphate isomerase, lactate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase that were similar in electrophoretic mobility to host tissue controls. Host allozymes were present on gels for only a fraction of the individual parasite samples examined and could be differentiated from parasite allozymes using host tissue controls. Based on these findings, it is suggested that host samples be included on each electrophoretic gel in genetic studies of parasites to reduce the likelihood of errors due to host enzyme contamination of parasite samples. PMID- 1919939 TI - Serum concentrations of extracellular matrix components: novel markers of metabolic control and hepatic pathology in glycogen storage disease? AB - Laminin, hyaluronic acid (HA), procollagen III amino-terminal propeptide (PIIINP), and procollagen I carboxy-terminal propeptide (PICP) concentrations were measured by radioimmunoassay or radiometric assay in sera from 21 patients with glycogen storage disease (GSD). Laminin was increased in 16 of 29 samples from the six children with GSD I, 25/43 from the seven with GSD III, and 3/19 from the eight with GSD IX; laminin correlated with serum aspartate aminotransferase and gamma-glutamyltransferase but not with serum triglycerides, cholesterol, lactate, or urate. HA was increased in 20% of samples from GSD I, 58% from GSD III, and in none from GSD IX; HA correlated with serum lactate and urate but not with liver function tests, serum cholesterol, or triglycerides. Serum PIIINP was increased in only eight samples and PICP in only one; children with poor linear growth had low PIIINP and PICP. Immunostaining studies of nine liver biopsies taken at diagnosis showed increased laminin and PIIINP staining in portal tracts, fibrous septa, and around sinusoids in periportal regions; children with a greater degree of immunostaining did not always show significantly higher values of serum laminin or PIIINP. We speculate that raised serum laminin may reflect fibrogenesis (but not necessarily established fibrosis) in response to tissue damage in GSD, raised HA may reflect disturbed sinusoidal endothelial cell function, and low PIIINP and PICP impaired somatic growth rather than intrahepatic pathology. PMID- 1919940 TI - Early liver transplantation is indicated for tyrosinemia type I. AB - Liver transplantation is now accepted as the treatment of choice for tyrosinemia type I (hereditary tyrosinemia). In an effort to determine whether any factors in these patients would aid in predicting optimal timing of the transplant procedure, we evaluated several clinical, biochemical, and radiographic parameters in five successive patients undergoing liver transplant for tyrosinemia type I at the University of Minnesota. All five patients evidenced prolonged periods of clinical and metabolic stability with dietary therapy and four of five remained stable at the time of evaluation for transplantation. Nevertheless, all five suffered significant and unexpected complications of tyrosinemia prior to the time of liver transplant. Four developed renal stones, two were in liver failure, and one developed a neurologic crisis that left him completely paralyzed. Hepatocellular carcinoma was found in one of the five at transplant. We could identify no clinical, biochemical, or radiographic study that was predictive of the likelihood of significant complications of the disorder. Survival from the transplant procedure itself was 100%. The inability to predict or prevent significant complications of tyrosinemia and the favorable outcome from transplantation lead us to recommend liver transplant for all patients with tyrosinemia type I by 12 months of age. PMID- 1919941 TI - Salmonella typhimurium appendicitis. AB - A child with signs and symptoms of acute gastroenteritis developed localization of her pain to the right lower quadrant. A clinical diagnosis of appendicitis was made and an inflamed appendix was found at surgery. The postoperative period was marked by high spiking fevers and profuse nonbloody diarrhea. Cultures of the appendix and the stool revealed Salmonella typhimurium. Nontyphoidal Salmonella organisms are a rare cause of acute suppurative appendicitis. Intraoperative cultures of the appendix and peritoneal fluid as well as postoperative cultures of the diarrheal fluid were crucial in elucidating the cause of this patient's unusual course. PMID- 1919942 TI - Fatal liver failure in two children with Niemann-Pick disease type B. AB - We report on two young patients with Niemann-Pick disease type B presenting with severe hepatic disease. Both children developed cirrhosis and died of intrahepatic block and mechanical hemolysis. Autopsy findings revealed complete obstruction of the sinusoids by lipid-laden Kupffer's cells. These two cases illustrate a new hepatic lesion of Niemann-Pick disease. PMID- 1919943 TI - Endoscopic removal of inflammatory esophagogastric polyps in children. AB - Two adolescent patients with inflammatory esophagogastric polyps (IEPs) are presented. In each case, the patients complained of chest pain and dysphagia. In one patient, there was no histological evidence of esophagitis in association with the IEPs. Their clinical course suggests that the presentation of IEPs in adolescents is indistinguishable from and may result in secondary gastroesophageal reflux and esophagitis. In each case, endoscopic polypectomy was utilized effectively as the mode of therapy. PMID- 1919944 TI - Erosion through the posterior gastric wall by a pancreatic pseudocyst secondary to gastric duplication. AB - Gastric duplications are the rarest form of enteric duplication. They account for about 20% of all gastrointestinal duplications. Delayed and missed diagnosis leads to prolonged morbidity and mortality. We report a case of a child with a gastric duplication cyst in the body of the pancreas, associated with a pancreatic pseudocyst that ultimately eroded into the posterior wall of the stomach. PMID- 1919945 TI - Testing the hypoallergenicity of a formula measuring intestinal permeability during provocation procedures. PMID- 1919946 TI - Innervation of total colonic aganglionosis examined by monoclonal antibody 171B5. PMID- 1919947 TI - Gastroesophageal reflux in children with chronic recurrent bronchopulmonary infection. AB - To evaluate the role of gastroesophageal reflux (GER) as a possible cause of recurrent bronchopulmonary infection in Chinese children, 23 patients were studied prospectively with 24-h pH monitoring. Their ages ranged from 3 to 25 months. The patients studied were chosen by the criterion of repeated, radiographically documented bronchopulmonary infection with a frequency of two or more episodes in the most recent 6 months, or a single episode with a protracted course longer than 3 months. Twenty-one of the 23 showed abnormal GER on 24-h pH monitoring. Twenty children received medical therapy, 17 of whom were followed regularly for 14-29 months. Eleven had subsidence or improvement of symptoms at follow-up. Follow-up pH monitoring was performed in 5 of the 11 patients, and showed improvement. Six failed to show improvement with medical therapy. Follow up pH monitoring revealed increased reflux in two of them. Three of the six received fundoplication and had marked improvement of reflux and symptoms postoperatively. Clinical resolution corresponded well to 24-h pH monitoring. GER may be considered one of the possible contributing factors in any child with chronic recurrent bronchopulmonary infection, and antireflux therapy might be beneficial. Twenty-four hour pH monitoring was the best single test for diagnosing GER and determining the severity of the disease. PMID- 1919948 TI - Esophageal pH monitoring data during chest physiotherapy. AB - Sixty-three infants, aged from 1 to 4 months, were examined for gastroesophageal reflux (GER) using esophageal pH monitoring. Thirty were examined because of chronic vomiting, 21 were healthy controls examined for GER as part of a screening program for sudden infant death syndrome, and 12 had an acute respiratory disease (RD). The 24-h pH monitoring data were within normal ranges in 26 infants (20 controls, 2 babies with emesis, and 4 with RD). Data were abnormal in 37 infants (1 control, 28 infants with emesis, and 8 with RD). All babies were submitted during a fasting awake period to a 30-min chest physiotherapy session. In the three groups studied, the incidence of GER episodes detected by the pH probe was significantly higher during physiotherapy if compared (a) to the calculated mean incidence during a 30-min period of the 24-h investigation or (b) to the incidence during a fasting awake period such as that during which the physiotherapy was given (p less than 0.001; Wilcoxon rank-sum test). We conclude that chest physiotherapy significantly increases GER incidence. We therefore propose restricting chest physiotherapy to fasting periods. These data add to the confusion that already exists regarding the possible causal relationship between (acid) GER and respiratory disease. PMID- 1919949 TI - The role of the exocrine pancreas in early-onset vitamin B12 malabsorption in gluten-challenged celiac children. AB - The fractional absorption of vitamin B12 (FAB12) was measured by a double-isotope technique specially adapted for children. In six celiac children on a strict gluten-free diet and with a normal small intestinal biopsy, the FAB12 performed in the fasting patient averaged 30% (23-40%). After gluten challenge for a mean of 2 months (range 1-4), when mucosal damage was demonstrated by biopsy, the average fasting FAB12 in these patients decreased to 10% (0-17%) (p less than 0.05). However, when the FAB12 test was repeated by means of stimulation by a B12 free meal 1-3 weeks later, while the patients were still on a diet containing gluten, a significant increase was observed (mean 21%, range 14-27%) (p less than 0.05). In four of the six patients the B12 absorption was further evaluated by repeating the FAB12 test by means of intravenous cholecystokinin (CCK) stimulation (n = 3) or by administration of exocrine pancreas enzyme supplementation (EPES) (n = 2) or cobinamide (n = 1). These tests all showed FAB12 values within the range of the meal-stimulated FAB12. Moreover, in eight gluten-free celiac children with normal biopsies, no difference was found between fasting and meal-stimulated FAB12 values. Therefore, it is likely that the early onset B12 malabsorption observed in the gluten-challenged celiac child with upper small-intestinal mucosal damage is in part due to an insufficient stimulation of the exocrine pancreas when using the standard fasting B12 absorption test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919950 TI - Clostridium difficile in inflammatory bowel disease relapse. AB - Stools of 65 patients with exacerbation of symptoms of inflammatory bowel disease were examined for the presence of enteric pathogens and Clostridium difficile. Ten (16%) had C. difficile toxin. Symptoms in all patients cleared after therapy, with improvement correlating with elimination of toxin from the stool. PMID- 1919951 TI - Measurement of colonic transit time in children. AB - Transit times through the whole colon and its segments were measured in 10 healthy children and 14 children suffering constipation secondary to myelomeningocele. The subjects ingested radio-opaque markers on three successive days, and on the fourth a plain abdominal roentgenogram was taken using fast film. In the healthy children, total colonic transit time (mean +/- SD) was 37.8 +/- 6.2 h, with segmental times of 10.8 +/- 3.5 h for the right colon, 12.2 +/- 2.7 h for the left, and 14.7 +/- 2.1 h for the rectosigmoid; upper normal limits of 17.8 h for the right colon, 17.6 h for the left, 19.1 h for the rectosigmoid, and 50.2 h for the total colonic transit time were established. In the constipated children, the total transit time was 59.9 +/- 5.4 h, with segmental times of 15.9 +/- 2.3 h for the right colon, 18.9 +/- 2.3 h for the left, and 25.0 +/- 2.6 h for the rectosigmoid. The technique described is simple, is easy to use in clinical practice, and involves a lower radiation dose than other methods. It may prove useful for measurement of colonic transit time in suitable patients. PMID- 1919952 TI - Realimentation of dehydrated children with acute diarrhea: comparison of cow's milk to a chicken-based formula. AB - A randomized, prospective study was performed on 73 male children between 3 and 14 months of age with mild to moderate dehydration caused by acute diarrhea, and who were rehydrated with WHO-ORS, and then at 4 h after admission were fed either cow's milk or an experimental diet based on chicken, plantain, and coconut oil. There were no statistically significant differences in the admission characteristics. The group of children fed cow's milk had a higher total volume of diarrheic evacuations (p less than 0.05). The average duration of diarrhea was 20 h shorter in the group of infants on the milk-free formula. A significant correlation was observed between the volume of diarrhea and the WHO-ORS consumed during the first 48 h, but not to the volume of diet intake. PMID- 1919953 TI - Evaluation of growth and changes in body composition following neonatal diagnosis of cystic fibrosis. AB - Early deficits in nutritional status that might require specific treatment and early response to nutritional therapy were studied longitudinally in 25 infants with cystic fibrosis (CF) diagnosed by neonatal screening, using anthropometric and research body composition methodology, and evaluation of pancreatic function. At the time of confirmed diagnosis (mean 5.4 weeks), body mass, length, total body fat (TBF), and total body potassium (TBK) were all significantly reduced. Following diagnosis and commencement of therapy there was a normalization of weight, length, and TBK by 6-12 months of age, indicating catch-up growth. But in some individuals the response was incomplete, and as a group, mean total body fat remained significantly lower than normal at 1 year of age. Seven of 25 (28%) were pancreatic sufficient at diagnosis, and all but one had evidence of declining pancreatic function requiring the institution of pancreatic enzyme therapy during the next 1-9 months. The median age of commencement of enzyme therapy was 10 weeks (range 5 weeks to 11 months). These longitudinal assessments emphasize the dynamic changes occurring in absorptive function, body composition, and nutritional status following neonatal diagnosis of cystic fibrosis and may reflect previously described abnormalities of energy metabolism in this age group. Abnormal body composition is evident in most CF infants following diagnosis by neonatal screening but pancreatic damage may still be evolving. We suggest that early active nutritional therapy and surveillance for changes in pancreatic function are warranted in CF infants diagnosed by neonatal screening. PMID- 1919955 TI - The curious umbilicus: clue to the cause of abdominal pain. AB - Omphalomesenteric duct derivatives cause an assortment of complications, most notably intestinal hemorrhage and obstruction. Intestinal obstruction is the most lethal complication and usually results from a diverticulum with an attachment to the umbilicus. This cause of intestinal obstruction is not generally recognized preoperatively. We report a teenager with episodic abdominal pain, acute small bowel obstruction, and a curious umbilical deformity with an underlying omphalomesenteric duct remnant. We believe that this physical finding suggests the diagnosis in patients with intestinal obstruction who have experienced unexplained episodes of abdominal pain. PMID- 1919954 TI - Lecithin:cholesterol acyltransferase (LCAT) activity during lipid infusion in premature infants. AB - Plasma cholesterol and lecithin concentrations are regulated by the serum enzyme lecithin: cholesterol acyltransferase (LCAT). LCAT activity is low in cord blood of premature infants, suggesting that in these infants the hypercholesterolemia associated with Intralipid infusion might be due to low LCAT activity. The serum LCAT activity has not been quantitated in preterm infants receiving intravenous fat emulsions. We have therefore quantitated LCAT activity in eleven premature infants maintained on total parenteral nutrition (TPN). Ten infants were studied during the first 2 weeks after birth; they received daily infusions of Intralipid at a rate of 0.5-2.0 g/kg/day over 15 h. One infant received 3.8 g/kg/day during the second week. In addition to LCAT, serum apoprotein A1 (the cofactor of LCAT), cholesterol, triglycerides, and free fatty acids were quantitated. Blood specimens were taken before the start of the infusion and 15-45 min before its completion. The LCAT activity and apoprotein A1 concentrations remained, respectively, 21-24% and 30-35% of adult levels. However, serum cholesterol levels remained in the normal range during the fat infusion. It remains to be established whether low LCAT activity and apoprotein A1 levels are due to the administration of Intralipid (which lowers LCAT activity in rats), to the lack of enteral feedings, or to prematurity per se. Our data suggest that administration of Intralipid at a rate not exceeding 1-2 g/kg/day does not impair the clearing of Intralipid-lecithin and the metabolism of cholesterol. PMID- 1919956 TI - Recurrent pancreatitis in three patients with chronic idiopathic intestinal pseudo-obstruction. AB - Chronic idiopathic intestinal pseudo-obstruction is a syndrome with substantial morbidity and mortality associated both with the syndrome and with its therapy. Standard therapy has included prokinetic agents and intravenous nutritional support when oral feedings are inadequate to maintain nutriture. We report three children with chronic intestinal pseudo-obstruction who experienced one or more attacks of pancreatitis. Two patients developed pseudocysts. One patient died. All three patients underwent cholecystectomy; one had stones, one had acalculous cholecystitis, and one had a normal gallbladder. All patients received prokinetic agents and total parenteral nutrition as therapy for their pseudo-obstruction. Candidate mechanisms to explain the etiology for pancreatitis in chronic intestinal pseudo-obstruction include biliary dysmotility associated with pseudo obstruction and excessive cholinergic stimulation due to therapy with prokinetic agents. PMID- 1919957 TI - Duodenojejunal intussusception secondary to hamartomatous polyp of Brunner's glands. AB - A case of duodenojejunal intussusception secondary to a large hamartomatous polyp of Brunner's glands was reported in a 15-year-old girl. Despite a great preponderance of ileocolic intussusception in childhood, this is the first reported case of duodenojejunal intussusception occurring in that age group. The diagnosis was not made by clinical examination; complete duodenal obstruction was shown in upper gastrointestinal series and by endoscopy. The intussusception was reduced manually at laparotomy, and the polyp was excised. Pathological examination revealed a preponderance of normal-appearing Brunner's glands in the tumor, consistent with the diagnosis of Brunner's gland hamartoma. PMID- 1919958 TI - Drug abuse prevention evaluation methodology: a bright future. AB - Drug abuse prevention research findings have been inconsistent. These inconsistencies can be related to several issues including study design and methodology. This article presents consensus recommendations developed to enhance drug abuse prevention evaluation research by a group of prevention researchers and practitioners who met at the National Institute on Drug Abuse in Rockville, Maryland during May 1989. As noted by the number of consensus statements, there was a high level of agreement. After exploring various aspects of evaluating prevention interventions, that agreement was reflected in specific recommendations which are directed to modifying prevention approaches; integrating epidemiologic, etiologic and intervention research methods; and expanding prevention research utilization. PMID- 1919959 TI - A survey of current research studies on drug education programs in America. AB - This article surveys recent research findings on drug education programs in America. Findings have been somewhat contradictory but a pattern of encouraging results seem to favor prevention programs that focus on resistance training. Research results were complimentary of D.A.R.E. (Drug Abuse Resistance Education) and S.A.P. (Student Assistance Program) which emphasizes intervention strategies. Experts noted that drug education programs require interagency collaboration among schools, communities, and families. Authorities appealed for a higher funding priority toward evaluating the effectiveness of drug education programs. The article also provides information about what parents, schools, students, and communities can do concerning drug prevention efforts. PMID- 1919960 TI - Using conceptual matrices, knowledge maps, and scripted cooperation to improve personal management strategies. AB - Research in the area of substance abuse suggests that ineffective personal management strategies appear to be a major factor in abuse behavior. In this study, fifty-seven students in an intermediate level psychology class were provided with three tools previously found to enhance academic learning strategies--knowledge maps, scripted peer cooperation, and conceptual matrices- as a means of understanding and improving personal management strategies. Student ratings of the value of these activities were significantly higher than an average or moderate response. Individual differences appear to be an important consideration in predicting participants' perceptions of the value of this approach. Those who felt they had control of whatever happens to them, and those who perceived problems as impactful and had strong desires to change recurring problem situations, had the most positive reactions to the types of activities used in this study. PMID- 1919961 TI - DIADS: computer-based system for development of school drug prevention programs. AB - The Drug Information, Assessment and Decisions for Schools (DIADS) is a computer based information and decisions support system for the development of school drug abuse prevention programs. DIADS provides access to a cost-effective planning resource that has information to programs about alcohol, other drugs, and prevention. Also, DIADS helps the school assess the effectiveness of its current prevention efforts using an expert-generated school assessment model containing fourteen factors. Feedback from the assessment provides suggestions for improvements in current prevention programs. DIADS guides the selection of future activities and helps in program planning. Pilot test of DIADS at several sites indicates school personnel find the information on DIADS helpful, timely and easy to access. PMID- 1919962 TI - Nonritual alcohol drinking practices among high school students from the Kibbutz movement in Israel: implications for prevention. AB - This article describes the Kibbutzim part of a survey conducted in the north of Israel during spring 1990, in order to investigate alcohol drinking habits of Jewish students from Kibbutzim and urban areas, as well as those of Moslem and Druze students, and to draw conclusions for designing alcohol abuse prevention activities. Of the general sample of 2763 students, 572 subjects were drawn from eleven schools which belong to sixty-two Kibbutzim. Exactly 435 students were Kibbutzim-born and 137 were outsiders living and being educated in the Kibbutzim. Kibbutzim-born youth showed the highest rate of involvement with alcohol in Israel, and a striking difference concerning the rates of alcohol consumption was revealed between the above mentioned two groups. This article explains this gap, as well as the high prevalence of alcohol use among Kibbutzim-born youth, and discusses implications for prevention. PMID- 1919963 TI - Age and alcohol, marijuana and hard drug use. AB - Developmental theories of adolescent alcohol, marijuana and hard drug use have emphasized the factor of age as an explanatory variable. However, studies have not attempted to examine the manner in which age interacts with other explanatory variables to predict usage. This article examines the interactive nature of age in predicting alcohol, marijuana and drug use based on a sample of 435 students from schools in a north-central county of Illinois. The results indicated statistically significant interaction terms for age with peer and social control factors for each type of usage. These findings suggest that many factors commonly associated with adolescent usage may be conditioned by age. The article also recommends that additional research examine the interactive nature of age, as well as other factors, when testing theories of alcohol, marijuana and drug use among adolescents. PMID- 1919964 TI - The place of sociology in a drug education curriculum. AB - This article gives consideration to the part a sociological perspective can play in a drug education curriculum. Sociology's study of human behavior from the context of various social groupings is considered appropriate to any understanding of drugs and drug use, as are a number of substantive areas common to the discipline. The sociological perspective is examined from the broad foci of structure and process, and with each focus examples of a sociological approach to drug use is offered. The common concerns of these approaches, as well as their points of divergence, are discussed. A sample outline of a course in "Drugs and Society" is also presented, suggesting the ways in which the sociological issues discussed could provide an orientation to the study of drug use in a social context. PMID- 1919965 TI - 17th annual Frank Costenbader Lecture. Amblyopia revisited. PMID- 1919966 TI - Predictors of prism response during prism adaptation. Prism Adaptation Study Research Group. AB - Results of the Prism Adaptation Study (PAS) indicate that prism adaptation improves the success rate of strabismus surgery for patients with acquired esotropia. Patients who show a fusion response to the prisms benefit most from this preoperative treatment. This study analyzes the characteristics of those patients who were and were not prism responders in the PAS. Significant factors predicting a prism response included: patients who were older at the time of onset of their esodeviation (P = .007), duration of deviation less than 1 year (P = .04), alternating fixation (P = .003), fusion on the Worth four-dot test at near with prism neutralization (P = .008), and equal vision (P = .009). Demographic characteristics were similar for both responders and nonresponders except that non-Hispanic patients were significantly more likely to respond to prisms than Hispanic patients (P less than .002). No test or characteristic was found which could reliably predict the prism response. Therefore, all patients with acquired esodeviations should be considered candidates for prism adaptation prior to strabismus surgery. PMID- 1919967 TI - Stability of the postoperative alignment in adjustable-suture strabismus surgery. AB - We reviewed the postoperative alignment drift in 201 patients between the ages of 14 and 75 years who underwent rectus muscle surgery with adjustable sutures from 1984 to 1989. We analyzed results for 42 primary esotropia (ET) surgeries and 37 reoperations (groups IA and IB, respectively), 34 exotropia (XT) primary surgeries and 66 reoperations (groups IIA and IIB, respectively), and 22 hypertropia (HT) surgeries (group III). Forty percent of patients required postoperative muscle adjustment. All patients underwent a minimum of 8-weeks follow up; 66% underwent 6-months follow up or longer. The postoperative drifts in alignment for primary surgeries versus reoperations were not significantly different for either ET or XT patients. The mean postoperative drift in prism diopters from the alignment immediately after the adjustment, or after the surgery if no adjustment was needed, for each group as measured during the most recent follow up was 1.3 eso-shift for group IA, 1.2 exo-shift for group IB, 4.8 exo-shift for group IIA, 4.1 exo-shift for group IIB, and 1.5 hyper-shift for group III. Only for groups IIA and IIB were these drifts found to differ significantly from zero. Based on these drift patterns, we align ET patients to orthotropia, XT patients to 5 to 7 delta esotropic, and HT patients to 1 to 2 delta hypotropic positions. PMID- 1919968 TI - Results of unilateral medial rectus recession in high AC/A ratio esotropia. AB - Twenty-five patients with high accommodative convergence/accommodation (AC/A) ratios and near esotropia of 15 to 35 prism diopters were treated with a 6- to 8 mm unilateral medial rectus recession according to the near deviation. In 24 patients (96%), the esodeviation was aligned within 10 delta, with a follow up ranging from 3 to 7 years. Only one patient had greater than 10 delta of esotropia (14 delta), and none became exotropic. This procedure appears to be a safe and effective method in the treatment of esotropia with high AC/A ratios, in a selected group of patients. PMID- 1919969 TI - Persistent pupillary membranes. AB - Extensive persistent pupillary membranes which occlude the pupil may occur in isolation or in association with other ocular anomalies. Amblyopia may result if the membranes are extensive. We favor nonsurgical intervention except if unusual circumstances are present as demonstrated in one of our two cases. PMID- 1919970 TI - Unilateral superior rectus recession for the treatment of dissociated vertical deviation. AB - The management of dissociated vertical deviation (DVD) is an unsettled issue. Several authors have advocated bilateral superior rectus recession for all patients with DVD unless a dense amblyopia is present in the nonfixating eye. Our experience suggested that DVD was being successfully treated with unilateral bilateral superior rectus recession. We reviewed the charts of 57 patients who underwent graded unilateral superior rectus recession and 10 patients who had bilateral superior rectus recession for the treatment of DVD. DVD, a manifest deviation, was considered as distinct from occlusion hyperphoria, a latent deviation present only under cover. Of the patients who underwent unilateral superior rectus recession, only six developed a significant (14 prism diopters or more) DVD in the unoperated eye. The presence of any DVD in the unoperated eye appeared to be predictive of an unacceptable postoperative deviation (15 times greater chance, P less than .001). Patients with an occlusion hyperphoria in the unoperated eye showed no increased propensity to develop a significant DVD following surgery. The results of bilateral surgery were disappointing. Eight of ten patients had residual DVD in one or both eyes of 10 delta or greater. Our results suggest that unilateral surgery is an effective treatment of DVD in patients with a manifest deviation in only one eye. Although neither unilateral nor bilateral surgery was entirely satisfactory for the treatment of bilateral DVD, we recommend bilateral superior rectus recession for these patients. PMID- 1919972 TI - Adenocarcinoma of the ciliary epithelium in a 12-year-old black child. AB - Histopathologic examination of a blind eye from a 12-year-old black girl revealed an unsuspected adenocarcinoma of the nonpigmented ciliary epithelium and evidence of previous penetrating trauma. The association between adenocarcinoma of the ciliary epithelium and ocular trauma has been well documented in elderly patients but not in children. The histopathologic distinction between a pleomorphic adenocarcinoma of the ciliary epithelium and a uveal melanoma may be difficult. Signs of previous penetrating trauma should heighten suspicion of an adenocarcinoma, even in young children. PMID- 1919971 TI - Testing stereopsis in the preschool child: is it clinically useful? AB - The evaluation of stereoacuity should provide an unambiguous assessment of binocular function in infants and young children. Unfortunately, clinical measures of stereopsis in these young patients often result in stereotheresholds poorer than the criteria suggested to differentiate normal from anomalous binocular vision. Thus, two experiments were conducted to determine whether the large stereothresholds frequently demonstrated on tests designed for young children are diagnostic of normal binocular function in preschool children. The first experiment investigated the salience of the monocular cues in the Lang and Frisby stereotests in normal preschool children (2 to 5 years old). None of the children who passed either the Frisby or the Lang stereotest under binocular conditions were able to pass either test monocularly, even after passing the test binocularly. In the second experiment, preschool children with abnormal binocular vision were tested with the Lang and Frisby stereotests to determine if large disparities (730 to 800 seconds of arc [arcsec]) could be passed without normal binocular vision. None of the children with strabismus passed either stereotest. However, two children with anisometropia passed the Frisby test and one of these children also passed the Lang test. These results suggest that in the absence of other clinical findings to the contrary, the demonstration of gross stereopsis with either the Frisby (730 arcsec) or Lang (733 or 800 arcsec) test in the preschool child implies normal binocular function. Thus, clinical tests of stereopsis for infants and preschool children, like those used routinely for adults, can provide evidence of binocular function without approaching stereothreshold. PMID- 1919973 TI - Strabismus fixus convergens secondary to amyloidosis. AB - Strabismus fixus convergens is a condition in which both eyes become fixed in extreme adduction. It can be congenital or acquired. We report a case of strabismus fixus convergens in a high myope with primary amyloidosis localized to the lateral rectus muscle. To our knowledge, this is the first report of a case of strabismus fixus convergens secondary to amyloidosis. PMID- 1919975 TI - Endophytic vs exophytic unilateral retinoblastoma: is there any real difference. PMID- 1919974 TI - Chorioretinal lacuna in the amniotic band syndrome. AB - The malformations in the amniotic band syndrome (ABS) are due to entrapment of fetal parts by fibrous band in the amniotic sac. Limbs are most commonly affected followed by craniofacial defects in one third of patients. Ocular defects include corneal leukomas and lid colobomas often contiguous with facial clefts, strabismus, hypertelorism, and microphthalmos. Unilateral chorioretinal defects or lacunae are rare findings in the ABS. We report a female infant with such a lacunar defect along with central nervous abnormalities, and discuss the differential diagnosis and the embryopathic implications. PMID- 1919976 TI - Occult spinal dysraphism in patients with anal agenesis. AB - Recent reports have suggested an association between congenital anorectal anomalies and occult spinal dysraphism. Eighty-seven patients with anal agenesis have been treated at this institution over the last 14 years. Two of these patients had spinal cord anomalies recognized at birth (a myelomeningocele and a tethered spinal cord). Two additional patients presented with progressive neurologic deficits in early childhood and were each found to have a tethered spinal cord. To further assess the magnitude of this problem, we have used magnetic resonance imaging (MRI) of the spine to survey prospectively 23 infants with anal agenesis. Twenty-one former patients who were asymptomatic were recalled and also studied. Four of 44 patients (9%) were found to have significant occult spinal dysraphism; each child had undergone neurosurgical operation without morbidity. MRI found each child to have a tethered spinal cord, either as an isolated lesion (2) or in association with a syrinx (1) or lipomyelomeningocele (1). One of these patients had a neurologic deficit detected on careful preoperative evaluation. The other three, two of whom were less than 2 years old, had no detectable deficit. Neither the extent of the anorectal malformation, the absence of associated congenital anomalies, nor the demonstration of normal vertebral anatomy on plain radiographs of the spine precluded the presence of occult spinal dysraphism. Therefore, we recommend that all patients with anorectal anomalies undergo MRI imaging of their spines during initial evaluation to screen for occult spinal dysraphism. In addition, consideration should be given to recalling older patients for MRI evaluation. PMID- 1919977 TI - Pericardial patch tracheoplasty for severe tracheal stenosis in children: intermediate results. AB - Between 1982 and 1990, 15 children have undergone pericardial patch tracheoplasty, 13 for complete tracheal rings and 2 for acquired tracheal stenosis. Eleven had complete tracheal rings from the thoracic inlet or the cricoid to the carina. Diagnosis was by bronchoscopy (15), computed tomography (10), and magnetic resonance imaging (3). As first described by Idriss in 1984, the surgical technique uses a median sternotomy approach, extracorporeal circulation, bronchoscopic guidance, and the use of pericardium as a tracheal patch. There was one perioperative death of mediastinitis (operative survival, 93%). There were two late deaths caused by complications of tracheostomy (1) and direct laryngoscopy and bronchoscopy (DLB) (1). Follow-up is complete in 12 intermediate-term survivors and ranges from 0.4 to 8.2 years (mean, 4.2 +/- 2.9 years). Five children required multiple DLBs with dilation and excision of granulation tissue; one of these patients underwent tracheoplasty revision 5 months after the initial procedure for residual tracheal rings, and four of these children have had tracheostomies, two temporary and two currently (4 months, 7 years). Seven children had widely patent tracheas observed at follow-up DLB with little or no residual stenosis after tracheoplasty. All survivors are currently asymptomatic, except for the two children with tracheostomies. Pericardial patch tracheoplasty offers effective therapy with relatively low operative mortality for infants and children with severe long segment tracheal stenosis. On intermediate-term follow-up, nearly all survivors are essentially free of symptoms of residual tracheal stenosis. PMID- 1919978 TI - Gonadotropins moderate rejection of trophic-specific congenic testes grafts. AB - Factors that favor graft survival of fetal and neonatal testis relative to adult testis were explored by studying the effects of rapid growth on immunogenicity. Tissue-specific growth was initiated by elevated gonadotropins created by oophorectomy and allografted target testes were examined. Three-day postnatal testes were implanted under the subrenal capsule of oophorectomized (as confirmed by elevated gonadotropins) and nonoophorectomized females. Immunosuppressive therapy with cyclosporine A was administered to selected animals of both groups. Preliminary studies in outbred rats and more extensive studies in allogenic/congenic mice (C57BL/6J to B10.A) showed that testicular allografts exposed to the elevated gonadotropins caused by previous host oophorectomy grow larger, have less lymphocytic infiltrate, and show better preservation of architecture than do allografts in nonoophorectomized female recipients. The graft survival resulting in vivo from elevated gonadotropins approximated that permitted by either maximal immunosuppression or syngeneic transplantation. PMID- 1919979 TI - Electrophysiologic and histological monitoring of MHC-matched and mismatched canine intestinal allografts. AB - Intestinal transplantation (ITx) has potential applications for the treatment of short-bowel syndrome (SBS). A major obstacle to its clinical use is rejection, which may partly be overcome by major histocompatibility complex (MHC) matching. At present, it is impossible to predict accurately the early onset of rejection. The aim of this study was to assess the value of in vivo measurements of transepithelial potential difference (PD) for the determination of rejection in MHC-matched and -mismatched canine ITx. A heterotopic ITx was performed in MHC tissue-typed Beagle dogs. Two ileostomies were created for PD monitoring and histology. Via one ileostomy, a well-defined segment of the IT, was isolated by a double balloon catheter and the intraluminal PD was measured in reference to a subcutaneous electrode. The PD responses during perfusion of a theophylline solution (crypt cell stimulation, PD theophylline) and during perfusion of a glucose solution (villus cell stimulation, PD glucose) were assessed. The results of in vivo PD measurements were compared with simultaneously obtained histology specimens. Four groups of dogs were studied: group 1 (controls, n = 10) ileal autotransplants; group 2 (n = 6) ileal allotransplants, fully mismatched; group 3 (n = 3) ileal allotransplants, 1 haplotype identical; and group 4 (n = 5), ileal allotransplants, fully matched. No immunosuppression was given. All dogs of group 1 survived indefinitely and both PD and histology showed no abnormalities. In group 2, 3, and 4 the onset of histological changes related to rejection corresponded well with decreased PD responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919980 TI - Growth failure and decreased levels of insulin-like growth factor I in obstructive jaundice are reversed by bile diversion. AB - Insulin-like growth factor I (IGF-I) is one of the principal stimuli of linear growth. Growth failure in children with chronic cholestatic jaundice may be related to decreased hepatic synthesis of IGF-I. It was hypothesized that (1) biliary obstruction would lead to growth retardation and decreased circulating IGF-I levels; and (2) surgical drainage of the obstructed biliary system would reverse these effects. To test this hypothesis, the following study of male Sprague-Dawley rats (135 g; 10 animals per group) was performed. Group I underwent common bile duct ligation (CDL); group II underwent choledochoduodenostomy 2 weeks following CDL; group III were sham-operated and fed with CDL rats; and group IV were sham-operated and fed ad libitum. Daily food intake and weekly body weight were recorded. Statistical analysis was by repeated measures analysis of variance and individual comparisons were evaluated by Student's t test. Biliary obstruction results in decreased food intake, rate of weight gain, and IGF-I levels. A significant reduction in IGF-I levels was also noted in the pair-fed sham-operated rats (group III). Relief of obstructive jaundice by surgical drainage results in a reversal of these changes. It is concluded that the growth failure and decreased IGF-I levels associated with obstructive jaundice can be reversed by surgical drainage of the obstructed biliary system and, in part, are due to inadequate nutrition. PMID- 1919981 TI - Impaired clearance and organ localization of Candida albicans in obstructive jaundice. AB - Sepsis is a major cause of morbidity and mortality in infants with cholestatic jaundice. This may be attributed to altered host defense mechanisms. Fungal infection frequently occurs in immunocompromised patients. This study evaluates the effect of biliary obstruction on blood clearance and organ localization of radiolabeled viable Candida albicans. Male Sprague-Dawley rats (140 to 150 g) were placed in 2 groups. Group I (n = 30) were sham-operated controls. Group II (n = 90) underwent ligation and division of the distal common bile duct (CDL). At 1, 2, and 3 weeks following CDL, 10(7) cells/mL radiolabeled viable C albicans were injected via the tail vein. The final distribution of the organisms was calculated and expressed as the mean percent of radiolabeled organisms per gram and per total organ. Blood clearance of C albicans was similarly rapid in both groups. However, there was a significant decrease in the trapping of fungi by the rat liver Kupffer cells (20.3% +/- 7.9% v control 42.5% +/- 15%; P greater than .001), and increased pulmonary localization of bacteria 3 weeks following CDL (53.6% +/- 13.2% v control 41.4% +/- 6.4%). The significant decrease in liver trapping and increased lung localization of C albicans in CDL rats, may result in systemic reemergence of fungi and play a role in the susceptibility to fungal infection in jaundiced subjects. PMID- 1919983 TI - Small intestinal transplantation in nonhuman primates. AB - Small intestinal transplantation represents a potentially therapeutic procedure for individuals with short gut syndrome. The purpose of this study was to develop a model for small intestinal transplantation in primates that is: technically feasible without microsurgery; consistent in the prevention of allograft rejection; functional in terms of nutrient absorption; and compatible with harvest for multiple organ procurement. First, autotransplantations on four rhesus monkeys were performed in order to study a variety of harvesting techniques and vascular anastomoses. Then, a study was performed with 14 heterotopic allotransplants in 4 baboons and 10 rhesus primates. The successful donor model consisted of division of the pancreas, harvesting the small bowel with a superior mesenteric artery and portal vein pedicle. The allograft vascular pedicle was anastomosed to the recipient's common iliac vessels in end-to-side fashion. The graft was transplanted as an out-of-continuity loop, both ends being exteriorized as stomas providing access for absorption studies and biopsy. Three immunosuppressive regimens were tested: (1) cyclosporine A (CyA) 20 mg/kg/d, solumedrol (SML) 2 mg/kg/d, and graft irradiation (150 rad) (n = 4); (2) CyA 20 mg/kg/d and SML 2 mg/kg/d (n = 3); and (3) CyA 40 mg/kg/d, SML 2 mg/kg/d, and azathioprine 5 mg/kg/d (n = 3). There were 4 deaths due to technical error in the first 24 hours. Weekly graft biopsy, serum CyA levels, complete blood count, and automated 24-channel serum analysis were performed. Grafts surviving greater than 14 days underwent absorption study via luminal perfusion with sucrose, maltose, dextrose, Pregestimil, xylose, and cyclosporine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919982 TI - Infectious complications of pediatric liver transplantation. AB - Twenty-five pediatric orthotopic liver transplantations (OLTs) performed in 22 patients at Sainte-Justine Hospital were reviewed for infections complications. One patient died within 12 hours posttransplantation and is excluded. The patients had an average age of 6.1 years (range, 1.25 to 19 years) and an average weight of 20.4 kg (range, 11 to 55 kg). Two patients (9%) were cytomegalovirus (CMV) seropositive and 9 of 19 patients (48%) were Epstein-Barr virus (EBV) seropositive preoperatively. Five of the donors (20%) were CMV seropositive. The most common indications for OLT were biliary atresia (8) and tyrosinemia (7). There were 4 deaths, for an overall mortality rate of 19%. In 3 patients, deaths were related to infection (CMV hepatitis and duodenitis with aortoduodenal fistula, adult respiratory distress syndrome [ARDS] with Streptococcus viridans pneumonia, Escherichia coli cholangitis with progressive hepatic failure). Fifteen patients (72%) had 41 major infections, most of them bacterial, during the first month posttransplantation. These include pneumonia (25%), line sepsis (17%), cholangitis (14%), and tracheitis (14%). There was only one major viral infection, a CMV hepatitis that occurred in the first month posttransplantation. Three patients had fungal infections (8%) associated with hepatic artery thrombosis and recurrent cholangitis. All three patients required retransplantation. There was only one protozoal infection (Pneumocystis carinii pneumonia) causing life-threatening respiratory failure, from which patient recovered without sequelae. Infection still remains a serious complication of OLT. Bacterial infection is common and is usually associated with technical complications. The low rate of CMV infection is related to low incidence of CMV in the donor pool and the minimal use of strong immunosuppressants. PMID- 1919984 TI - Intralipid adversely affects reticuloendothelial bacterial clearance. AB - Lipid emulsion is a major caloric source in patients receiving total parenteral nutrition. Cleared by the Kupffer cells of the reticuloendothelial system (RES), lipid emulsion may adversely affect the RES function by decreasing its ability to remove blood-borne bacteria. This study evaluates and compares the blood clearance and organ localization of viable radiolabeled [35S] Escherichia coli following slow intraperitoneal (IP) and more rapid intravenous (IV) administration of a 20% fat emulsion (FE). Sixty male Sprague-Dawley rats weighing 150 g were placed in 6 experimental groups (10 rats per group). Group 1 received IP normal saline (3 mL/d for 3 days); group II received IP FE (20%) (4 g/kg/d for 3 days); and group III received normal saline IV (3 mL/d for 3 days). The remaining animals received a slow (15-minute) IV infusion of FE (4 g/kg/dose) prior to bacterial challenge: group IV at 4 hours; group V at 24 hours; and group IV at 4 and 24 hours. E coli (10(9)/mL) were injected via the tail vein. Blood samples were obtained for clearance study. At 10 minutes, tissue samples (50 to 100 mg) of liver, spleen, kidney, and lung were obtained and processed for liquid scintillation counting. Although rapid bacterial blood clearance was found in all the groups, there was a significant change in organ localization of bacteria. Normal distribution of bacteria in group I was as follows: liver 70.1% +/- 6.2%, spleen 5.2% +/- 1.2%, kidney 0.2% +/- 0.04%, and lung 1.6% +/- 0.6%. There was a slight increase in lung localization of bacteria in rats receiving IP FE (3.7% +/ 1.5%; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919985 TI - Low-fat, high-carbohydrate diets improve wound healing and increase protein levels in surgically stressed rats. AB - The specific effects of omega 3 and omega 6 polyunsaturated fatty acids on wound healing, nutrition status, or immune function are controversial. Therefore, we investigated the effects of fatty acid supplementation on wound healing and nitrogen retention in a surgically stressed rat model. Male Sprague-Dawley rats (weighing 250 g) were placed into three isocaloric, isonitrogenous feeding groups (controls [standard Vivonex]; 30% safflower oil [omega 6]; or 30% fish oil [omega 3]) for 8 days prior to receiving subcutaneous vascular graft wound cylinders in their dorsal midline. Nitrogen balance was monitored daily. Wounds healed for 10 days, animals were then euthanized, serum was drawn, and wound cylinders were harvested for analyses. The low-fat, high-carbohydrate control group had higher serum albumin levels at 10 days than either fatty acid-supplemented group (3.5 +/ 0.4 g/dL v 2.9 +/- 0.3 g/dL and 2.7 +/- 0.2 g/dL, omega 3 and omega 6, respectively; both P less than .05) and had better nitrogen balance (8.6 +/- 0.8 mg N/d v -2.6 +/- 0.9 mg N/d and 0.8 +/- 1.2 mg N/d, omega 3 and omega 6, respectively; both P less than .05). They also had better healed wounds at 10 days (450 +/- 290 micrograms 5-hydroxyproline [OHP]/cm of wound cylinder v 150 +/ 40 micrograms OHP/cm and 145 +/- 90 micrograms OHP/cm, omega 3 and omega 6, respectively). Surgically stressed rats had higher protein levels, better nitrogen balance, and improved wound healing when fed a diet high in carbohydrates and low in fat. PMID- 1919986 TI - A tungsten-supplemented diet delivered by transplacental and breast-feeding routes lowers intestinal xanthine oxidase activity and affords cytoprotection in ischemia-reperfusion injury to the small intestine. AB - Ischemia-reperfusion injury has been implicated as playing a major role in the development of necrotizing enterocolitis, a major cause of morbidity and mortality in the newborn. A tungsten-supplemented molybdenum-free diet can reduce xanthine oxidase (XO) enzyme activity in the intestine, which in turn reduces the generation of oxygen radicals after an ischemia-reperfusion insult. This study evaluated the ability of this diet to be effective by indirect means, ie, transplacental and breast-feeding routes. XO activity of the intestine was measured in three groups of CD-1 white rats: I, weanlings fed the tungsten diet or standard chow for 1 week; II, 1-day-old rat pups whose mothers were maintained on the tungsten or standard chow for 7 to 10 days prior to term; and III, rat pups at 1 and 3 weeks after birth whose lactating mothers were maintained on the tungsten or standard chow. Some animals from group III also underwent either a 30 or 60-minute episode of occlusion of the superior mesenteric artery (SMA) to evaluate the protective effects of the diet. XO activity was significantly reduced in all groups receiving the tungsten diet (P less than .0001). Blinded histopathologic studies of the entire small bowel showed significantly less villar necrosis (P less than .05) and fibrosis (P less than .0001) in the tungsten-treated group than in the controls. In the 60-minute occlusion study all tungsten-group animals survived, whereas 7 of 12 in the control group died of intestinal infarction within 24 hours (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919987 TI - The effects of an arginine-free enteral diet on wound healing and immune function in the postsurgical rat. AB - Critically ill patients have increased rates of sepsis partly due to a down regulated immune system. Nutrients may modulate the immune system. The following studies were performed to determine whether arginine is one of these "essential" nutrients for the immune system. Thirty-two male Sprague-Dawley rats (weighing 175 g) were divided into two groups that were pair-fed with either an elemental, arginine-supplemented enteral diet, or the same diet with arginine removed and replaced with glycine. Both diets were isocaloric, isoosmolar, and isonitrogenous. After 6 days on the diet, animals underwent testing. There were no significant differences between the arginine-supplemented and the arginine free diet groups in blood glucose or hematocrit. The arginine-supplemented animals had higher serum albumin (4.1 +/- 0.1 mg/dL v 3.6 +/- 0.1 mg/dL; P = .035) and serum protein levels (5.2 +/- 0.1 mg/dL v 4.3 +/- 0.1 mg/dL; P = .041); and had higher thymus gland (0.53 +/- 0.03 g v 0.44 +/- 0.02 g; P less than .0001) and spleen weights (0.66 +/- 0.01 g v 0.57 +/- 0.01 g; P less than .01). Daily total urinary nitrogen excretion, nitrogen balance, and weight gain showed a tendency for the arginine-supplemented animals to retain more of their nitrogen calories. There was no difference in the amount of hydroxyproline (OHP) found in the wound cylinders of either group (both 25.6 micrograms OHP/cm polytetrafluoroethylene) but the arginine-supplemented group's wounds had greater wound bursting strengths (429 +/- 3 g/cm v 350 +/- 7 g/cm; P = .044).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1919989 TI - Balloon tracheoplasty in children: results of a 15-year experience. AB - Strictures of the trachea traditionally have been dilated by antegrade bouginage. This method not only dilates but imparts a shearing force to the wall of the trachea. The resultant trauma may contribute to further scarring and aggravation of the stricture. We report a 15-year experience with 37 patients and 158 tracheal dilatations using balloon catheters that impart only radially directed forces and can be precisely placed and gradually inflated. Various adjunctive techniques have been performed, including: (1) electrocautery of granulation tissue; (2) parenteral and local use of steroids; and (3) intraluminal stenting after dilation. Recent experience indicates that this combination of methods is important in improving patient outcome. The principal indications for balloon tracheoplasty include acquired tracheal stenosis from various causes, and congenital subglottic stenosis. Almost all patients received some immediate benefit from balloon tracheoplasty. Fifty-four percent of the patients achieved long-term improvement (with a minimum follow-up of 2 months). Additionally, 10 of 20 children who had been unable to previously tolerate removal of an indwelling tracheostomy tube proceeded to extubation. We have had poor success in treating bronchial and glottic stenosis. Endoscopically directed hydrostatic balloon tracheoplasty is a safe and effective method for the treatment of tracheal stenosis of varying causes. Multiple dilatations are required that gradually improve the character of the tracheal lumen. In selected cases, the procedure may delay or avoid the need for an open tracheoplasty. PMID- 1919988 TI - Midgestational excisional fetal lamb wounds contract in utero. AB - Clinical observations and experimental data suggest that fetal wound healing is very different from adult wound healing. An understanding of the biology of scarless fetal wound healing has tremendous clinical potential for modulating postnatal wound problems. In this study, the fetal lamb model was used to assess excisional fetal skin wound contraction in utero. Full-thickness 9-mm punch biopsy wounds were created on fetal lambs at 100 days' gestation (term, 145 days). Half of the wounds remained exposed to amniotic fluid, whereas the other half were covered by a silastic patch to exclude amniotic fluid. Wounds were harvested 3, 7, or 14 days later and wound areas were calculated. Exposure to amniotic fluid retarded wound contraction significantly at 3 days, but by 14 days all wounds had completely contracted and reepithelialized. Myofibroblasts are an important cellular element of wound contraction. The presence of wound myofibroblasts was documented by both transmission electronmicroscopy and immunocytochemistry with antimuscle actin antibody. It is concluded that fetal lamb wounds contract in utero and exposure to amniotic fluid appears to retard fetal skin wound contraction only during the early healing process. PMID- 1919990 TI - Laryngotracheoesophageal cleft (type IV): management and repair of lesions beyond the carina. AB - Since the first successful repair of a complete laryngotracheoesophageal cleft (LTEC) to the carina in 1982, three newborn infants were observed with a particularly difficult variant in which the cleft extends beyond the carina into the mainstem bronchi. This type IV LTEC creates a long common tracheoesophagus, whose successful separation requires meticulous preoperative, operative, and postsurgical care. Three infants had complete surgical repair at our institution at 29, 49, and 225 days old and survived a minimum of 8 months. Recurrent tracheoesophageal fistulae at the thoracic inlet occurred in two infants, but was not observed in one patient when sternocleidomastoid muscle was interposed between the trachea and esophagus in the neck. Microgastria is an associated finding in each infant with the tracheoesophageal cleft extending beyond the carina. The small stomach is problematic as it is anatomically inadequate for any antireflux procedure and has not grown well, even with prolonged feeding. Early cleft repair is essential to prevent the development of chronic lung disease secondary to recurrent aspiration. The techniques to make the diagnosis, the preferred treatment to initially protect the airway, a single-stage operation performed simultaneously through the chest and neck to definitively repair the cleft, and finally the intraoperative and postoperative management critical for an optimal outcome are described. PMID- 1919991 TI - Operative strategy for recurrent laryngeal cleft: a case report and review of the literature. AB - A case is reported of recurrent laryngotracheoesophageal cleft following two attempted repairs. The anterior approach to the larynx and trachea provided excellent exposure for defining the extent of the recurrent cleft, and allowed precise anatomic repair. Neurovascular structures were easily avoided by this operative method. Of 170 clefts reported in the literature, 19 recurred necessitating reoperation. The anterior approach to the larynx and trachea is appropriate in recurrent clefts and may be preferable at the initial repair. PMID- 1919992 TI - Congenital adenomatoid malformation of the lung: current management and prognosis. AB - A retrospective 10-year review of congenital adenomatoid malformation (CAM) included 10 cases diagnosed in utero by ultrasound and 13 cases that presented postnatally. Two prenatally diagnosed cases were aborted because of associated lethal anomalies. All remaining patients underwent resection. Up to one third of all cases, whether diagnosed prenatally or postnatally, were asymptomatic. Resection is recommended to avoid respiratory distress, infection, or associated malignancy. There were 5 nonsurvivors, including 2 therapeutic abortions and 3 who died postoperatively. All had either polyhydramnios or ascites. All patients who died postoperatively had a respiratory arrest at birth and underwent immediate lobectomy. All died on the first day of life after a brief period and were found to have associated pulmonary hypoplasia. One had undergone a prenatal transthoracic cyst aspiration at 34 weeks gestation in an attempt to allow lung growth and prevent premature labor. Prenatal ultrasound findings suggestive of poor prognosis included polyhydramnios, ascites, mediastinal shift, and noncystic type III CAM. However, there is a spectrum of severity of CAM. The lesion can either regress and be asymptomatic at birth, or it can progress to cause either fetal death from hydrops or neonatal death caused by associated pulmonary hypoplasia. These findings should be considered in prenatal counseling for CAM. PMID- 1919993 TI - Lesser curvature gastrostomy reduces the incidence of postoperative gastroesophageal reflux. AB - Gastrostomy is frequently required in children with neurological impairment and feeding disability. In some centers, concomitant (prophylactic) antireflux procedures are often performed due to the increased risk of occurrence of significant gastroesophageal reflux (GER) after isolated operative or percutaneous endoscopic gastrostomy placement. This has been documented in both experimental and clinical settings. A recent clinical study suggests that placement of a gastrostomy in a lesser curvature location rather than on the greater curvature of the stomach may decrease the incidence of postoperative GER. The purpose of this study is to evaluate this clinical impression. Under ketamine anesthesia and sterile technique, 30 cats underwent laparotomy and placement of a Stamm gastrostomy tube; 15 (group A) were located on the greater curvature of the stomach. Each animal was evaluated postoperatively for the occurrence of GER using upper gastrointestinal contrast study, nuclear medicine gastric scintigraphy (technetium 99m), pH probe/Tuttle test, and lower esophageal sphincter (LES) manometrics. Contrast esophagram with barium demonstrated GER in 3 animals in group A and none in group B (P less than .05). The pH/Tuttle test was positive in 4 animals in group and none in group B (P less than .05). 99mTc gastric scintigraphy (over a 30-minute period) demonstrated GER in 7 cats in group A and in only 1 cat in group B (P less than .05). LES manometric pressures were similar among both groups. This study suggests that a gastrostomy placed in the lesser curvature may reduce the incidence of postgastrostomy GER and obviate the need for a concomitant antireflux procedure in patients with a severe feeding disability but without demonstrable GER during preoperative assessment. PMID- 1919994 TI - Alkaline gastroesophageal reflux in infants and children. AB - The incidence of alkaline gastroesophageal reflux (GER) was examined in 111 consecutive children referred for evaluation of GER during a 1-year period. The results of 24-hour pH monitoring studies and the medical records were retrospectively evaluated. Acid reflux was defined as occurring whenever the pH was less than 4 and alkaline reflux was defined whenever the pH was greater than 7. The percentage of time that reflux occurred, the number of reflux episodes, the number of episodes greater than 5 minutes, and the longest episode were all recorded. Based on these data, four categories of patients were identified as compared with normal values as determined by Pellegrini et al. When using criteria based on the percentage of time that reflux occurred, the largest group of children with GER was found to reflux acid (50%). However, 27 children (24%) had combined acid and alkaline reflux. Eighteen (16%) had predominantly alkaline reflux. Previously, these 18 children would have been considered as having a low likelihood of reflux by pH criteria. Endoscopic examination showed that pathological evidence of esophagitis occurred in four of the children with pure alkaline reflux. This review shows that symptomatic GER in infants and children may be due to acid or alkaline secretions or a mixture of both. A previously unrecognized cohort exists of children who demonstrate primary alkaline reflux. These patients need to be recognized and may benefit from a therapeutic program specifically designed to control alkaline reflux. PMID- 1919995 TI - Basilar skull fractures in childhood with cranial nerve involvement. AB - Cranial nerve palsies developed in 23% of 73 children with basilar skull fractures. The majority occurred in patients 10 years of age or older. Our overall incidence was higher than that in a review in which basilar skull fractures were indiscriminately included with all head injuries. Our experience with meningitis was similar to that present in the literature and would seem to support avoidance of prophylactic antibiotics. Because there was no improvement in neurological deficits in patients treated with steroids (the only case of meningitis in our series was associated with steroids), we believe that their use is unwarranted. It is important to discuss the prognosis with the patient's family, because, although the majority (53.3%) of cases resolve completely, those with residual deficits can have significant morbidity. PMID- 1919996 TI - Pediatric cervical spine fractures: predominantly subtle presentation. AB - Previous description of cervical spine fractures in children have emphasized high mortality injuries to the upper cervical vertebra. Our experience suggests a much wider spectrum of injury. The medical records of all children with cervical spine fractures admitted to Children's Hospital between January 1, 1985 and December 31, 1989 were reviewed. The average age of the 50 patients was 11 years (range, 2.7 to 18.8 years) and 62% were boys. Motor vehicle-related accidents (54%), sports injuries (18%), and falls (12%) accounted for the majority of the fractures. Twenty-nine patients (58%) had an associated head injury. Fifty percent of the patients were transported from the accident scene and 44% were interhospital transfers. All patients receiving medical care prior to referral had appropriate cervical spine stabilization. On admission 30% of the patients were unresponsive. Thirty-one children were alert and verbal at the time of evaluation and 30 complained of neck pain and tenderness (97%). Twenty-five of the 31 patients (83%) had no demonstrable neurological deficit on initial physical examination. Lateral cervical spine radiographs were diagnostic in 49 children (98%). A relatively even distribution of fractures occurred at all levels of the cervical spine. The anatomic site of the injury did not correlate with age. Sixteen patients (32%) died. Of the 34 who survived, only 6 had a persistent neurological deficit. Children with cervical spine fractures have two distinct patterns of presentation: lethal or intact. The majority of children with cervical spine fractures presented with no complaints of neck pain and/or tenderness need a complete radiographic evaluation of their cervical spine. PMID- 1919997 TI - When the foundation slips. PMID- 1919999 TI - Hair loss in children and adolescents. AB - No other body system is more exposed to the public eye than the skin and the hair. Pediatric nurse practitioners (PNPs) frequently encounter patients in their practice settings with the complaint of "hair loss." The most often diagnosed causes of hair loss include tinea capitis, alopecia areata, traction alopecia, and trichotillomania. This article defines these conditions, explores the causes for them, and describes the incidences. Emphasis is placed on the PNP's role on making a differential diagnosis based on the presenting clinical manifestations, patient history, and laboratory testing. Treatment for these conditions as well as nursing goals and PNP interventions for management and family education also are discussed. PMID- 1919998 TI - Contraceptives for teenagers. AB - The contraceptive options suitable for teenagers are presented and discussed. Condoms have the advantage of preventing the spread of sexually transmitted diseases, and oral contraceptives are probably the most effective in preventing pregnancy. Other options include the barrier contraceptives available to women, spermicides, sponges, intrauterine devices, periodic abstinence, and the morning after pill. PMID- 1920000 TI - Evaluation of the child with acute abdominal pain. AB - Acute abdominal pain is a frequent and potentially serious episodic complaint. Evaluation of the child with acute abdominal pain is always challenging, even for the experienced nurse practitioner. Some of the difficulties include obtaining accurate historical information and the subleties of abdominal examination. However, approaching the differential diagnosis of acute abdominal pain from a developmental perspective may assist the nurse practitioner in coming to a more timely and accurate diagnosis. Pertinent historical data and techniques of examination are reviewed. Age-specific causes of acute abdominal pain and their clinical manifestations are presented. PMID- 1920002 TI - Dispelling common myths about HIV infection. AB - Myths and misconceptions about human immunodeficiency virus (HIV) are prevalent in both the lay and health care populations. It is imperative that health professionals have accurate knowledge about HIV infection and feel comfortable as they educate parents and children about this major health problem confronting society. Health care providers are always looking for innovative ways to approach the subject of patient teaching. Thus, this quiz was developed as a teaching tool to educate parents and older children about HIV infection. You can use the following true/false quiz or parts of it in any type of practice setting to teach about HIV infection and to dispel the myths and misconceptions that surround this illness. After your clients have completed the quiz, go over their responses with them using the explanation or rationale provided in the key for each answer. PMID- 1920001 TI - Computer-assisted decision making: a strategy for primary prevention of substance abuse. AB - A series of six computer-assisted instruction (CAI) programs were developed for primary prevention of substance abuse. The target population, objectives, content, and strategies for the programs were determined from three sources: a literature review of prevention research, theories of learning, and principles of instructional design regarding use of computer technology. Because the focus of the programs is on helping children make responsible choices, the central theme of the programs is on improving decision making. PMID- 1920003 TI - Precocious puberty. PMID- 1920004 TI - Child with prolonged cough. PMID- 1920005 TI - Medicaid reimbursement and pediatric nurse practitioners. (State-by-state analysis). PMID- 1920006 TI - The injury Prevention Program (TIPP). PMID- 1920007 TI - The electron microscopic immunolocalization of a copper-zinc superoxide dismutase in association with collagen fibers of periodontal soft tissues. AB - Periodontal soft tissues were cleaved from freshly extracted human teeth. Tissues were then prepared for subsequent biochemical and morphological studies according to the following plan: 1) immediate immersion in liquid nitrogen for the biochemical assay of superoxide dismutase (SOD); 2) immediate fixation prior to routine preparation for routine transmission electron microscopy; 3) immediate fixation prior to preparation for electron microscopic immunohistochemistry. Biochemical analysis showed that the human periodontal ligament contained about twice as much SOD activity as human skin (dermis), but considerably less enzyme activity than that seen in red blood cells. Interestingly, periodontal SOD activity appeared to decrease with age. Immunohistochemistry localized enzyme activity to the periphery of matrix collagen fibrils and to the glycocalyx of tissue fibroblasts. The pathophysiology of this enzyme regarding inflammatory diseases such as periodontitis is discussed. PMID- 1920008 TI - Dentinal tubule occlusion and root hypersensitivity. AB - Previous studies have established that root sensitivity is due in part to open dentinal tubules at the root surface. The purpose of this study was to longitudinally evaluate the occlusion of dentinal tubules by various clinical procedures including scaling and root planing and the application of potassium oxalate. A model was developed to evaluate dentinal surfaces in vivo. Six 2 mm x 3 mm sections were taken from the roots of extracted teeth immediately below the CEJ. One half of the treated dentin samples from each donor was incorporated into the removable denture worn by the donor and the other half served as baseline. The dentin samples were evaluated at 1 week by scanning electron microscopy. At day zero no open tubules were observed in any of the samples due to the presence of a smear layer or oxalate crystals. Evaluation of root planed samples revealed that by 7 days the tubules had re-opened. The samples which had been treated with potassium oxalate showed few oxalate crystals by 7 days revealing open tubules. Control samples were etched with EDTA and evaluated in the same manner. Although the number of tubules did not significantly change in the EDTA etched control samples, the diameter of the tubules dramatically decreased by 4 weeks. It can be concluded that the creation of a smear layer or application of oxalates to occlude dentinal tubules to reduce sensitivity are relatively short-lived. These procedures may provide patient comfort prior to natural occlusion of the tubules. PMID- 1920009 TI - The use of sustained release delivery of chlorhexidine for the maintenance of periodontal pockets: 2-year clinical trial. AB - The release of chlorhexidine from an ethyl cellulose-based dosage form (SRD) has been shown to be effective in the reduction of the flora associated with periodontal pockets as well as in reducing probing depths. In this study, treatment with this dosage form was compared to routine maintenance therapy (RMT) in a 2-year, split mouth clinical trial. Ten patients with 84 pockets greater than or equal to 5 mm who had not received any periodontal therapy or systemic antibiotics over the last 6 months were included. The patients all received a full mouth scaling and root planing together with through oral hygiene instruction. Two months later (baseline) plaque index (P1I), bleeding on probing (BOP), pocket probing depth (PD), and attachment levels (AL) were assessed at all selected sites. Pockets on the control side then received RMT while the experimental pockets were treated with the SRD only. Treatment was repeated every 3 months for 2 years. The SRD treatment resulted in an improvement of greater than or equal to 3 mm in PD of at least 1 pocket in 8 of 10 patients, while RMT resulted in a similar improvement in only 1 of 10 patients (P = 0.012). Similarly a gain of attachment of greater than or equal to 3 mm was found in at least 1 SRD pocket in 8 of 10 patients. The RMT resulted in a similar improvement in only 2 patients (P = 0.012).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920010 TI - The effect of chlorhexidine treatment of root surfaces on the attachment of human gingival fibroblasts in vitro. AB - Chlorhexidine mouthrinse is a widely used adjunct in periodontal therapy due to its bactericidal effects. The effect of this agent on chronic gingivitis and wound healing following surgical therapy in animals and humans has been favorable. The re-establishment of lost connective tissue attachment to the root surface following periodontal therapy is a desirable goal in which the ability of periodontal ligament fibroblasts to reattach to root surfaces of periodontally involved teeth is a critical event. Understanding the effect of chlorhexidine on fibroblast attachment will provide the rationale for its use during the healing phase of periodontal surgery. For this study, impacted third molars were sectioned into 4 pieces. Groups of 10 root pieces were exposed to 0.12% chlorhexidine or saline for 3 minutes followed by a distilled water rinse. The root pieces were incubated with human gingival fibroblasts (HGF) using standard tissue culture techniques for 1, 2, 4, 6, and 8 hours. HGF were prelabeled with 3H-thymidine to a standard specific activity. The surface area of each root piece was determined and the attached cells quantified by using scintillation spectroscopy. The number of cells per unit area was then calculated and the data expressed as cells/mm2. The repeated measures design was statistically analyzed by repeated measures analysis of variance. There was a significant difference between the number of attached cells in the chlorhexidine and the control groups (P less than 0.001). Exposure of root surfaces to chlorhexidine significantly inhibits subsequent fibroblast attachment which may interfere with regeneration of the periodontium. Hence, the data suggest that efforts should be made to minimize chlorhexidine contact with the root surface with physical barriers. PMID- 1920011 TI - Isolation and purification of bacteriocin from Prevotella intermedia (Bacteroides intermedius). AB - Thirty-three out of 46 strains of Prevotella intermedia (Bacteroides intermedius) isolated from gingival deposits of patients with adult periodontitis possessed the ability to inhibit growth of P. intermedia strain ATCC 25611, and 6 of the 33 showed strong inhibitory activity. Thirteen isolates did not have the ability to inhibit the growth of P. intermedia strain ATCC 25611. An inhibition factor from one of the isolates, P. intermedia TH14 which had strong inhibition, was purified and characterized. Bacteriocin TH14 activity was effective against only P. intermedia ATCC 25611 and Fusobacterium nucleatum, but not against other crevicular bacteria, including P. intermedia ATCC 33563, Porphyromonas gingivalis (Bacteroides gingivalis), Capnocytophaga sputigena and Actinobacillus actinomycetemcomitans. Streptococci, actinomyces, and veillonellas were not inhibited by bacteriocin TH14. Bacteriocin TH14 was heat sensitive, proteinaceous with molecular weight of 1,700 daltons and inhibited the growth of strain ATCC 25611 in 15 minutes. The growth inhibition of P. intermedia ATCC 25611 by bacteriocin TH14 was found to be due to the bactericidal activity of the bacteriocin. PMID- 1920012 TI - Effect of zinc upon cell attachment and proliferation on periodontally-diseased root surfaces. AB - The purpose of this study was to determine the effect of zinc ions on fibroblast attachment to periodontally-diseased root surfaces in vitro. Extracted periodontally-diseased teeth were treated with 0.5% ZnCl2 by iontophoresis at 0.5 mA for 2 to 6 minutes. Control groups were untreated diseased and untreated healthy teeth. Sections of the root underlying the pocket were cut from the diseased teeth. The specimens were incubated for 18 hours with L929 mouse fibroblasts, then transferred and incubated in cell-free medium for 48 hours. Cell attachment was evaluated by cell counts and scanning electron microscopy (SEM). Root surfaces were sampled with an acid-etch technique and zinc was measured with an atomic absorption spectrophotometer. Two samples from each group were examined for cell attachment with SEM. Data were analyzed using the appropriate statistical methods. The results showed that diseased, untreated root surfaces had significantly fewer cells attached; however, zinc iontophoresis did not significantly improve cell attachment to the diseased root surfaces. Zinc analysis showed that diseased, untreated root surfaces had a higher zinc content than healthy ones. SEM examination showed striking differences in cell attachment to healthy versus diseased root surfaces. The data indicated that zinc iontophoresis did not significantly enhance cell attachment to root surfaces of diseased teeth. PMID- 1920013 TI - The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing. AB - Polypeptide growth factors are a class of potent natural biologic mediators which regulate many of the activities of wound healing including cell proliferation, migration, and metabolism. Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) have been shown to regulate DNA and protein synthesis in bone cells in vitro and to interact synergistically to enhance soft tissue wound healing in vivo. We have hypothesized that the combination of PDGF and IGF-I may, therefore, enhance regeneration of both the soft and hard tissue components of the periodontium. To test this hypothesis we performed conventional periodontal surgery on all 4 quadrants of the mouth of 13 beagle dogs with naturally occurring periodontal disease. Following flap reflection, degranulation, and root planing, all premolar teeth in 2 quadrants of each dog received a combination of 3 micrograms of recombinant PDGF-B and IGF-I in a methylcellulose gel, while the premolar teeth in the contralateral quadrants received the gel alone. Teeth in 4 additional animals also received 125I-PDGF or 125I-IGF-I in the treated sites. The clearance rate of the 125I-labeled protein, changes in local bone metabolism, and amount of new bone and cementum with inserting collagen fibers were measured. The clearance studies revealed that the half-life of the factors at the site of application was 3.0 hours for IGF-I and to 4.2 hours for PDGF-B. Greater than 96% of the radio-labeled proteins was cleared by 96 hours and no radioactivity was detected 2 weeks after application. There was a significant (P less than 0.01) 2 fold increase in uptake of the bone-seeking radiopharmaceutical Technetium 99-MDP at 2 and 4 weeks in growth factor treated sites compared to controls, indicating that there was increased metabolic activity within the bone at these sites. Computer-aided histologic analyses of biopsies obtained at 2 and 5 weeks post operatively revealed a significant (P less than 0.01), 5 to 10 fold increase in new bone and cementum in PDGF-B/IGF-I treated sites at both time points compared to controls receiving the placebo gel. The height and total area of new bone continued to increase from 2 to 5 weeks. The new bone underwent a normal maturation process as judged by histologic appearance. A physiologic periodontal ligament space was also formed between the new bone and new cementum. There was no increase in ankylosis in the treated sites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1920014 TI - Errors in measuring parameters associated with periodontal health and disease. AB - The intra-examiner reliability for the Plaque Index (PII), Calculus Index (CI), Gingival Index (GI), and periodontal loss of attachment (LA) was evaluated in 2 different physical and clinical environments. Examiner reliability for each index was consistently better when clinical evaluations were performed in an office setting on subjects who had low levels of periodontal disease than under more difficult field conditions evaluating subjects with higher disease levels. In an office environment intra-examiner reliabilities were very good for subject-based averages (intraclass r's were 0.85, 0.83, 0.81, and 0.78 for GI, PII, LA, and CI, respectively); they were moderate to good for site-based scores (kappas were 0.63, 0.54, and 0.47 for CI, GI, and PII). Under field conditions reliabilities ranged from excellent to fair for subject-based averages (intraclass r's of 0.98, 0.86, 0.76, and 0.33 for LA, CI, GI, and PII, respectively); for site-based scores they ranged from moderate to fair (kappas of 0.50, 0.49, and 0.21 for GI, CI, and PII, respectively). Small but significant systematic errors were detected under field conditions for the PII and CI, and for the PII in the office environment as well. The results observed suggest that the examination process can affect the clinical status of the surface or site when replicate assessments of plaque and calculus are conducted within a 24-hour period. Our results also confirm that measurement error standard deviation for loss of attachment evaluated with a periodontal probe can be maintained at 0.13 mm for whole-mouth means and 0.54 mm for individual sites, even when examining subjects with substantial periodontal disease under field conditions. PMID- 1920015 TI - Halitosis measurement by an industrial sulphide monitor. AB - Previous studies have established that hydrogen sulphide and mercaptans are the primary components of halitosis (bad breath). In the present investigation, we report a simple, rapid technique for measurement of halitosis-related sulphides. The technique is based on a portable instrument generally used for environmental safety applications. Seventy-five volunteers were measured using this technique, and the results (in peak ppb hydrogen sulphide equivalents) compared with organoleptic assessment by 7 judges. A highly significant overall correlation (r = 0.603; P less than 0.001) was obtained between these 2 methods. Moreover, in most cases, the organoleptic ratings of the individual judges correlated more highly with sulphide monitor values than with one another. The simplicity of the technique suggests its use in clinical studies as well as in diagnosis and treatment of patients with this complaint. PMID- 1920016 TI - Lipid composition and biosynthesis in the gingiva of the domestic cat. AB - Periodontal disease in the domestic cat may assume debilitating and serious consequences; however, little is known of the biochemical composition or metabolism of feline gingiva in health or disease. In this report the chemical composition and metabolism of gingival lipids from inflamed an non-inflamed sites is presented and compared to other species with naturally occurring periodontitis. The neutral and phospholipid composition of feline gingiva was found to be distinct from that of porcine and human. As a measure of de novo lipid synthesis, the total incorporation of 14C-acetate into fractionated lipid components was determined and revealed an approximate 2 to 3 fold decrease in inflamed versus non-inflamed gingiva. The decrease in 14C-acetate incorporation appeared to result from a 2-fold increase in free acetate pools in inflamed compared to non-inflamed gingival samples, since total lipase and phospholipase activity were comparable in inflamed and non-inflamed gingiva and total lipid composition was not changed between inflamed and non-inflamed sites. These data are similar to those reported for periodontally involved human gingival tissue and suggest a common effect of periodontal inflammation on lipid metabolism in both species. PMID- 1920017 TI - Human periodontal cells initiate mineral-like nodules in vitro. AB - A primary objective in the treatment of periodontal diseases is the regeneration of the mineralized and soft connective tissue components of the attachment apparatus. Current theories suggest the cells of the periodontium have the capacity, when appropriately triggered, to actively participate in restoring connective tissues, including mineralized tissues. To evaluate further the role of such cells in periodontal homeostasis, periodontal ligament (PDL) cells and gingival fibroblasts (GF) were cultured and examined for alkaline phosphatase levels and for the ability to produce mineralized nodules in culture. These are two characteristics of osteoblast-like cells in vitro. The levels of alkaline phosphatase produced by these cells were determined by a modified kinetic assay and the ability of these cells to produce mineral-like nodules in vitro was evaluated by Von Kossa staining and light and electron microscopy. PDL cells had significantly higher levels of alkaline phosphatase when compared with gingival fibroblasts obtained from the same patient and the same passage, in vitro. Furthermore PDL cells, but not GF, were capable of producing mineral-like nodules in vitro. These results indicate differences in behavior between PDL cells and GF; such differences may prove important in designing appropriate clinical therapies directed at stimulating periodontal regeneration. PMID- 1920018 TI - Tissue levels of bone resorptive cytokines in periodontal disease. AB - The levels of 3 bone resorptive cytokines, interleukin 1 alpha (IL-1 alpha), IL-1 beta, and tumor necrosis factor alpha (TNF alpha), were assessed in tissues from sites of periodontal disease. As determined by ELISA of tissue extracts, IL-1 beta and TNF alpha were detected in all diseased sites, whereas IL-1 alpha was present in 8/22 sites, IL-1 beta was present in highest concentration (mean +/- SEM: 11,695 +/- 2,888 pg/ml; 672 pM), followed by TNF alpha (434 +/- 135 pg/ml; 26 pM), and IL-1 alpha (342 +/- 160 pg/ml; 20 pM). The levels of all 3 mediators were significantly lower in clinically healthy tissues. There was a highly significant correlation between levels of IL-1 beta and TNF alpha (rs = 0.61, P less than 0.001), suggesting coordinated expression of these 2 mediators. The numbers of cells containing each mediator was also determined by indirect immunofluorescence on frozen tissue sections. Consistent with findings from tissue extracts, IL-1 beta-containing cells were present in approximately 5-fold higher numbers than TNF alpha-containing cells, and 40-fold higher numbers than IL-1-alpha-containing cells. Taken together with previous findings, these results indicate that IL-1 beta is likely to be an important mediator in the pathogenesis of periodontal disease. PMID- 1920019 TI - Prevention of infective endocarditis: a review of the medical and dental literature. AB - This paper is a review of what is presently known about the cause and prevention of infective endocarditis. Systemic antibiotics alone are not always enough for an effective prevention of infective endocarditis. Non-streptococcus bacteria frequently found in the periodontal pocket are now reported as causing infective endocarditis; these bacteria are not uniformly susceptible to the antibiotics recommended for prophylaxis. Animal studies indicate that periodontal disease does increase the incidence of infective endocarditis and that the number of microbes entering the blood stream may not be as important in the production of infective endocarditis as other qualities, such as the microbe's ability to adhere. Antibiotics may affect the ability of a microorganism to adhere to tissues of the heart, but this association is yet unclear and may vary with the antibiotic and species of bacteria. Reduction of inflammation of the periodontal tissues is of the utmost importance in the prevention of infective endocarditis; however, mouthrinses have a very limited effect in a periodontal pocket of more than 3 mm in depth and irrigation of a periodontal pocket may create a dangerous bacteremia. Nevertheless, in addition to systemic antibiotics, local antimicrobial agents followed by routine dental treatment and maintenance show promise as an effective means for the prevention of infective endocarditis. Future research in the prevention of infective endocarditis should include placement of antimicrobials in the periodontal pocket and systemic agents that reduce platelet adhesion. The suggestions presented in this review are only recommendations for further research and are not to be construed as a substitute for the current guidelines. PMID- 1920020 TI - Smoker's melanosis. A case report. AB - Smoker's melanosis is a benign pigmentation of the oral mucosa, predominantly observed on the attached anterior mandibular gingiva and interdental papillae. These macular lesions are independent of genetic factors, therapeutic medication usage, and various systemic disorders. As a group they are often seen after the third decade of life. Due to the onset in adulthood and the progressive darkening, malignant melanoma must be ruled out. A review of the literature and a case report of this interesting and unique entity is presented. PMID- 1920021 TI - Videodensitometrical study of the alveolar bone crest in periodontal disease. AB - The relative mineral content per unit volume of bone in the alveolar bone crest was determined in 81 bone crests from 25 human autopsy cases by means of contact microradiography and videodensitometry of 100 microns thick sections. Each bone crest was divided in 4 areas: crestal, mesial, distal, and trabecular; and the relative mineral content was determined for each area. The data were analyzed statistically and it was found that the crestal area had a significantly lower mineral content than the other 3 areas. Histologically, the crestal area had a reduced number of Sharpey's fibers and it was speculated that these features lower the probability of restoring the natural crestal shape and the fiber reattachment, increasing the risk of bone loss. No correlation was found between relative mineral content and age or extent of inflammatory infiltration of the periodontal tissues. PMID- 1920022 TI - Periodontal disease in heterosexuals with acquired immunodeficiency syndrome. AB - We studied the prevalence and severity of periodontal disease among 181 heterosexual men and women with AIDS. Included were 167 (92%) intravenous drug users (IVDU) and 14 sexual partners of persons at risk for AIDS. Periodontal disease was seen in 71 of 78 (91%) women compared to 75 of 103 (73%) men. Gingivitis was the most severe form of periodontal disease in 7 (9%) women and 15 (15%) men. Increased severity of periodontal disease was seen in women as compared with men (P less than .001); among subjects with periodontitis, 48 (75%) of 64 women had moderate to advanced disease compared to 32 (53%) of 60 men. For individuals with periodontitis, the extent of involvement was associated with severity; 90% of subjects with advanced periodontitis had all 4 quadrants affected. Concurrent oral manifestations of AIDS, including candidiasis, hairy leukoplakia, ulcers and Kaposi's sarcoma were present in 167 (92%) subjects. We conclude that HIV-associated gingivitis and HIV-associated periodontitis are common in heterosexual men and women with AIDS and are often accompanied by other oral manifestations of AIDS. The reason periodontal disease is more severe in women is not known. Clinicians should be aware that these disorders occur in heterosexuals as well as in homosexual men. Further study will be necessary to delineate the pathogenesis of these disorders. PMID- 1920023 TI - Psychoanalytic interpretation of the Rorschach: do we have better hieroglyphics? AB - Schafer (1954) advanced the "Psychoanalytic Interpretation in Rorschach Testing" and asserted that thoughtful interpretation involved more than translating hieroglyphics or scores. In this book, he presented his thesis by describing four defensive styles (repression, denial, projective, and obsessive-compulsive) at various levels of severity of psychopathology. To investigate whether the Structural Summary data from Exner's (1986) Comprehensive System, with its improved reliability and validity and additional scores, allow one to make similar distinctions among the types of defense and severity of disturbance, we rescored the Schafer records. The results of this conservative test of Exner's system suggest that (a) the Comprehensive System reliably distinguishes the repressive style from the other styles, and (b) scores alone may provide adequate measures of severity of disturbance even with form quality excluded. We concluded that Rorschach scores must be understood as complex products of multiple psychological operations and may correspond to different subjective experiences in various contexts. PMID- 1920024 TI - Aging and terminal changes in Rorschach responses among the Japanese elderly. AB - The Rorschach Inkblot Test was used to examine how personality changes among the elderly and whether significant changes precede death. Six measurements were conducted over 10 years. The original subjects were 236 healthy Japanese elderly with an average age of 76.4 years; 52 subjects survived throughout the 10-year study. Age-related changes were reflected in the number of responses; responses regarding rejection, shading, and popular; poor form level (F-%); and content range. The changes in these variables suggest that productive and creative thinking, cooperativeness, and concerns for and interests in society lessen with advancing age. Over the 4 to 6 years preceding death, the popular responses and content range declined, and the decline accelerated before death. Tests within 2 years of death showed less animal movement response (FM), and higher form (F%), F %, and human content (H%) compared to the survivors. These results suggest that productivity, vital energy, and ego strength become reduced prior to death, whereas interest in and sensitivity to others is maintained to the end. PMID- 1920025 TI - Indications of depression and distress in divorce and nondivorce children reflected by the Rorschach test. AB - The appearance of depressive features, as reflected by responses to the Rorschach test, were explored in two groups of children from divorced and nondivorced families (referred to here as divorce and nondivorce children). The relationships between the depression scores and the children's hostility, aggression, and anxiety levels were also studied. The Rorschach Inkblot Test was individually administered to a nonclinical sample of 108 Swedish school children between 10 and 12 years old. The subjects constituted two groups, a divorce group (27 girls, 27 boys) and a nondivorce group (27 girls, 27 boys). Divorce children scored significantly higher on Exner's (1986) Depression Index than their nondivorce peers. Furthermore, divorce children with depressive features in their Rorschach responses were found to have a high level of hostility and aggression (as manifested in their Rorschach protocols), whereas no such associations were found among nondivorce children. PMID- 1920026 TI - Validity of the M Test: simulation-design and natural-group approaches. AB - The utility of the M Test (Beaber, Marston, Michelli, & Mills, (1985) as a screening measure for malingering was assessed using simulation-design (subjects asked to fake mental illness) and natural-group (forensic assessment cases suspected of malingering) approaches. A total of 318 subjects from community, clinical, and correctional settings completed the M Test under instructions to respond honestly or to simulate a major mental disorder. A factor analysis of the M Test items supported the original rationally based scale assignment, and the scales were found to have adequate internal reliability. To examine the predictive validity of the M Test, results revealed that sensitivity using the cutting scores suggested by Beaber et al. (1985) was much higher for simulating subjects (79.8%) than for the suspected malingerers (40.0%). The findings emphasize the danger of exclusive reliance on simulation studies for validating measures of malingering. It was concluded that, in its present form, the M Test does not constitute a good screening measure for assessing malingering. PMID- 1920027 TI - The Animal Preference Test and its relationship to behavioral problems in young children. AB - We compared performance on the Animal Preference Test; (APT; Van Krevelen, 1955) with parental assessment of children's behavioral problems as measured by the Achenbach Child Behavior Checklist (CBCL; Achenbach & Edelbrock, 1986). Forty Black and Hispanic 6- to 12-year-old boys were asked to name the three animals they would most like to be and the three animals they would least like to be if they could not be a human being. Reasons for animal choice were categorized into one of four theme categories: aggression, autonomy, nurturance, and pleasure beauty. Each category had a high degree (91%) of interrater reliability. When reasons for animal choice were dichotomized into aggression/autonomy versus nurturance/pleasure-beauty, children who rejected animals because of their nurturant or aesthetic qualities displayed significantly greater aggressive (p less than .001) and depressed (p less than .05) behaviors on the CBCL. The choice of animals the subjects would most like to be was not meaningfully associated with CBCL performance. Further research with this easily administered and reliably scored projective test appears warranted. PMID- 1920028 TI - Further validation of the Satisfaction with Life Scale: evidence for the cross method convergence of well-being measures. AB - The structure of subjective well-being has been conceptualized as consisting of two major components: the emotional or affective component and the judgmental or cognitive component (Diener, 1984; Veenhoven, 1984). The judgmental component has also been conceptualized as life satisfaction (Andrews & Withey, 1976). Although the affective component of subjective well-being has received considerable attention from researchers, the judgmental component has been relatively neglected. The Satisfaction With Life Scale (SWLS; Diener, Emmons, Larsen, & Griffin, 1985) was developed as a measure of the judgmental component of subjective well-being (SWB). Two studied designed to validate further the SWLS are reported. Peer reports, a memory measure, and clinical ratings are used as external criteria for validation. Evidence for the reliability and predictive validity of the SWLS is presented, and its performance is compared to other related scales. The SWLS is shown to be a valid and reliable measure of life satisfaction, suited for use with a wide range of age groups and applications, which makes possible the savings of interview time and resources compared to many measures of life satisfaction. In addition, the high convergence of self- and peer-reported measures of subjective well-being and life satisfaction provide strong evidence that subjective well-being is a relatively global and stable phenomenon, not simply a momentary judgment based on fleeting influences. PMID- 1920029 TI - Assessment of coping: an empirical illustration of the problem of inapplicable items. AB - The prevalence and effects of inapplicable items on the Ways of Coping Questionnaire (WOC) were studied. Three hundred seventy-six college students completed the WOC twice, referring to both heterogeneous (i.e., different types of) and homogeneous (the same) stressors. In addition to the standard procedure for administering this questionnaire, subjects were asked to identify items that were inapplicable to the stressors with which they were coping. Item inapplicability ranged from 2.1% to 83.9%, with a mean of 21.5% inapplicability across all WOC items. Application of a correction for item inapplicability demonstrated that situational effects are confounded by this phenomenon and may not hold up when the correction is applied. Implications of these findings include the possibility that previous research has over- or misidentified situational effects on coping. PMID- 1920030 TI - Early memories as expressions of relationship paradigms: a preliminary investigation. AB - Earliest childhood memories (EMs) have been utilized as expressions of relationship paradigms, but few empirical studies have been conducted. This study outlines the construction and development of an EM relationship scoring system and scale utilizing nonclinical and clinical samples. It was hypothesized that relationship episodes could be reliably coded using EMs and that they would demonstrate convergent validity with measures of attachment style (Separation Individuation Test of Adolescence), mood (Profile of Mood States), and clinical symptomatology (Symptom Checklist 90-revised [SCL-90-R] and the Minnesota Multiphasic Personality Inventory [MMPI]). The hypotheses received broad support. Findings indicate that relationship episodes may be reliably coded from EMs. Associations between individual EM variables, the EM relationship scale, and objective measures suggest that the quality of relationships expressed in EMs is associated with degree of general maladjustment. Suggestions for further research are discussed. PMID- 1920031 TI - The Nuremberg mind redeemed: a comprehensive analysis of the Rorschachs of Nazi war criminals. AB - We examined a blind, actuarial analysis of the Rorschach data of the Nuremberg war criminals (NWC) using Exner's (1974) Comprehensive System in an attempt to prove the convergence of the NWC construct along dimensions of psychological (personality) functioning and to prove its discriminability from other appropriate psychiatric and nonpsychiatric comparison groups. The weaknesses of previous research methodologies are examined and discussed vis-a-vis the historical and theoretical developments of the concepts of authoritarianism, dogmatism, obedience to authority, and the development of the Rorschach Inkblot Technique. PMID- 1920032 TI - The Rorschach M response: a return to its roots. AB - The Exner (1986) system of scoring of the Rorschach results in a human movement response (M), which is far afield from Rorschach's original intent. This divergence can easily lead to faulty interpretations of a record as there is no need for kinesthetic reactions on behalf of the subject in Exner's system. The need to return to a traditional view of the M is demonstrated through a focus on theory and the literature that illustrates Rorschach's intent. The alteration of the M results in a scoring system which, due to its differences, must come up with a separate interpretative system and not consider itself part of the Rorschach system that Rorschach envisioned. PMID- 1920033 TI - Comments on "the Rorschach M response: a return to its roots". AB - These comments address three interrelated issues posed in Kramer's article concerning Rorschach's definition of the M response and the criteria for M that is applied in the Comprehensive System, the possibility that M may be overscored by the criteria for the Comprehensive System, and the issue of whether the Rorschach is amenable to quantification and empirical scrutiny. Kramer has oversimplified and misconstrued statements by Rorschach, Beck, and Bohm; in reality, the criterion for the scoring of M responses in the Comprehensive System differs very little, if at all, from that suggested by Rorschach. The accumulated history of the test seems to confirm that it is amenable to quantification and empirical scrutiny. PMID- 1920034 TI - The Masculinity-Femininity Scale of MMPI-2: is it useful with normal men? AB - Using ratings provided by significant others, we examined characteristics of 819 normal men whose scores on the Masculinity-Femininity scale (Scale 5) of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) ranged from low to high. Also examined were the possible effects of educational level as a moderator variable. Only one external characteristic was correlated with Scale 5 scores at a level of significance that could not be attributed to chance, and that correlation was negative, whereas previous literature indicated a positive relationship. The findings were essentially the same whether or not the effects of education were controlled. Regardless of Scale 5 scores and the higher the men's educational levels, the more positive were ratings by their partners. In general, the results do not support the usefulness of Scale 5 in describing the personalities and behaviors of normal men. PMID- 1920035 TI - Confidence intervals for the MMPI-2. AB - The confidence intervals for the Minnesota Multiphasic Personality Inventory (MMPI-2) clinical scales were investigated. Based on the clinical scale reliabilities published in the MMPI-2 manual, estimated true scores, standard errors of measurement for estimated true scores, and 95% confidence intervals centered around estimated true scores were calculated at 5-point MMPI-2 T-score intervals. The relationships between obtained T-scores, estimated true T-scores, scale reliabilities, and confidence intervals are discussed. The possible role of error measurement in defining scale high point and code types is noted. PMID- 1920036 TI - Predicting with the MMPI the adjustment of juvenile delinquents to institutionalization: does gender make a difference? AB - Relationships between Minnesota Multiphasic Personality Inventory (MMPI) scales and criteria were evaluated to determine if the MMPI is gender biased when considering a juvenile delinquent population. The MMPI was administered to 549 juvenile delinquents: 105 Black men, 37 Black women, 331 White men, and 76 White women. In addition, behavioral and rating measures were collected; they served as adjustment criteria. Except for the criterion assessing neurotic symptomatology, equations that regressed criteria on MMPI scales neither underpredicted nor overpredicted for a gender. The MMPI tended to underpredict ratings of neurotic symptomatology for women. Significant differences in correlation coefficients for Black men and women occurred for the behavioral, nonrating criteria. Scale 4 was the best predictor for Black men, whereas Scales, 8, F, 1, and 2 tended to be the best predictors for Black women. Some possible explanations for these results are offered. PMID- 1920037 TI - Human figure drawings of adjudicated and nonadjudicated adolescents. AB - We investigated differences between human figure drawings of adjudicated and nonadjudicated adolescents. In addition, the relationship between human figure drawings and crime category (person, property, other, none) was examined for the adjudicated adolescents. Subjects consisted of four groups of adolescents (n = 25 each): adjudicated males, adjudicated females, nonadjudicated males, and nonadjudicated females. Human figure drawings were obtained from all subjects; they were scored using a system that was developed for use with adolescents. Kruskal-Wallis one-way analyses of variance (ANOVAs) were used to assess the effects of adjudication status and gender. There were 11 significant differences between adjudicated and nonadjudicated adolescents and 11 differences among the four groups. Results of Kruskal-Wallis ANOVAs also showed two significant differences among crime categories. PMID- 1920038 TI - Assessment of attention deficit disorder using a thematic apperception technique. AB - Attention deficit-hyperactivity disorder (AD-HD) is regarded as being relatively common among school-age children, but the literature reveals a number of confounding factors with standard assessment techniques of the disorder. Using a structured thematic apperception technique (the Tell-Me-A-Story [TEMAS] test) to measure attention to pictorial stimuli depicting characters, events, settings, and covert psychological conflicts, a study was conducted with 152 normal and 95 clinical Hispanic, Black, and White school-age children. Results reveal that the AD-HD children are significantly more likely than normal children to omit information in the stimuli about characters, events, settings, and psychological conflicts. Differences between the groups are large and persistent in the presence of structured inquiries by the test examiners. Results suggest the potential utility of structured thematic apperception techniques for the assessment of AD-HD, eventually to facilitate DSM-III-R (American Psychiatric Association, 1987) diagnosis, but also to invite closer scrutiny in carefully controlled validity studies. PMID- 1920039 TI - Is awareness of bodily change in emotion related to awareness of other bodily processes? AB - To what extent is reported attentiveness to bodily responses in emotion predicted by a general disposition to be attentive to one's normal, nonemotive bodily processes? University undergraduates (373 women and 167 men) completed the modified Autonomic Perception Questionnaire (APQ-R; Mandler, Mandler, & Uviller, 1958; Shields, 1984) for one of two target emotions, anger and transient anxiety, and the Body Awareness Questionnaire (BAQ; Shields, Mallory, & Simon, 1989), a measure of attentiveness to nonemotive bodily processes. In addition, the Body subscale, part of a Love Symptom Checklist concerning symptoms of romantic love was completed by 246 of these subjects. We predicted that the two measures of attentiveness to bodily response in emotion would be more strongly related to each other than to the BAQ. Significant low positive correlations between APQ-R and BAQ scores were obtained for each sex for both anger and anxiety. Correlations between the Body subscale and the APQ-R were high, positive, and significant, but correlations with the BAQ were near zero. Hierarchical multiple regression analyses showed that of the three variables entered (subject sex, Body subscale scores, and BAQ scores), the greatest change in explained APQ-R variance was accounted for by the Body subscale scores. This pattern of results was replicated in a second study of 56 women and 42 men. Results are discussed with reference to detected arousal in emotion and beliefs about emotion symptoms. PMID- 1920040 TI - The effect of pinealectomy and autonomic denervation on crypt cell proliferation in the rat small intestine. AB - Previously it has been found that pinealectomy in rats was associated with increased small bowel crypt cell proliferation. The hypothalamus is thought to play a role in the neural control of crypt cell proliferation and the pineal gland is known to be functionally connected with this component of the autonomic nervous system. Consequently, the effect on crypt cell mitotic rate of pinealectomy with autonomic denervation of the rat small bowel (local sympathectomy and truncal vagotomy) was observed to determine the possible importance of the autonomic nervous system in the mediation of the effects of pinealectomy on the crypts. It was found that interruption of either the vagal or sympathetic nerve supply to the small intestine both significantly decreased the usual hyperproliferative effect on the crypt cells observed after pinealectomy. It is suggested that the overall effect of the pineal gland is to suppress the crypt cell proliferation rate and that this effect is mediated, at least to some extent, by (1) the direct connections between the pineal gland and the hypothalamus, (2) the connections between the hypothalamus and the vagal and sympathetic innervation of the gut, and (3) the influence of the autonomic innervation on the activity of the enteric plexuses in relationship to the crypts. The pineal may have a role in modulating the local control mechanism of crypt cell proliferation. Its exact role in the control of crypt cell proliferation has not yet been defined. PMID- 1920042 TI - Pineal influence on the diurnal rhythm of nonspecific immunity indices in chickens. AB - The effect of pinealectomy and melatonin injections on the diurnal rhythms of serum lysozyme and blood granulocytes was examined in White Leghorn cockerels kept from time of hatching for 5 weeks in L:D 12:12 conditions and immunized twice with sheep red blood cells (SRBC). Pinealectomy or sham-operation was made during first week of life. Pinealectomized chickens were injected daily with a melatonin dosage increased over 4 consecutive weeks (the dosage was 10, 13, 16, and 20 ng per bird daily during the 4 weeks, respectively; MEL I) at the beginning of darkness. The same treatment was performed on chickens with an intact pineal gland using additional melatonin doses increased 10 times (MEL II) and 500 times (MEL III). Intact chickens were also injected with MEL II and MEL III 4 hr before the end of light. Control birds received equivalent injections of vehicle. Five-week-old chickens were sacrificed during a 24-hr period every 4 hr. The existence of diurnal rhythm was evaluated by cosinor analysis. Pinealectomy shifted the acrophase of the diurnal rhythm of granulocytes and abolished that of serum lysozyme. Both rhythms were restored in pinealectomized chickens by MEL I but not by vehicle injections. The same melatonin dose was unable to change the granulocyte rhythm but delayed the acrophase of that of serum lysozyme in chickens with an intact pineal gland. Two higher melatonin doses influenced the diurnal rhythm of granulocytes as a function of dose and time of administration. The rhythm of serum lysozyme was dependent only on the time of injection. The pineal gland seems to control, via its hormone melatonin, the diurnal rhythm of nonspecific immunity in chickens. PMID- 1920041 TI - Purinergic receptors have no major role in control of the circadian rhythm in rate of thymidine incorporation by cultured chick pineal glands. AB - We have examined the effects of some analogues of adenosine upon the circadian rhythm in rate of thymidine incorporation by cultured chick pineal glands. Incorporation in the early period of the photoperiod on day 2 of culture was slightly inhibited by the adenosine analogue N-ethylcarboxamido-adenosine, but this effect was not countered by the antagonist 8-phenyl-theophylline. Thymidine incorporation was inhibited when glands were continuously exposed to the adenosine transport inhibitor nitrobenzyl-thioinosine, but ongoing incorporation was not inhibited by addition of this agent. Removal of adenosine and deoxyadenosine supplements from the medium, with or without further addition of adenosine deaminase, had no appreciable effects upon thymidine incorporation. We conclude that adenosine and analogues probably play no role in regulation of the rhythm in rate of thymidine incorporation. PMID- 1920043 TI - Melatonin and the coding of day length in male Syrian hamsters. AB - Two experiments investigated the response of the pituitary-gonadal axis of pinealectomized male Syrian hamsters to programmed systemic administration of melatonin. In the first experiment, castrated male Syrian hamsters were housed in a short photoperiod (8L:16D) and maintained on subcutaneous testosterone implants for 7 weeks. These males were then pinealectomized or sham-pinealectomized and their testosterone capsules removed. Daily infusions of melatonin 250 ng/infusion) or its vehicle were administered for 3 weeks; infusion duration was long (11 or 12 hr) or short (6 hr). Measurement of serum luteinizing hormone (LH) following this 3-week period indicated that long-duration melatonin infusions mimicked short-day conditions (LH levels were low), but short-duration infusions did not (LH levels were significantly elevated). In the second experiment, pinealectomized, gonadally intact males were housed in a 12L:12D photoperiod and injected once daily with melatonin or its vehicle, either 3 or 5 hr after dark onset for 11 weeks. These times were chosen to coincide with the light:dark cycle phase that according to published reports is optimally responsive to exogenous melatonin for the induction of short-photoperiodic effects. Melatonin injections did not induce gonadal regression in pinealectomized hamsters. Melatonin and vehicle-treated males responded similarly; their testis widths and serum testosterone levels were not significantly different at the end of the experiment. These results support the hypothesis that the duration of melatonin secretion each night is an important variable in conveying photoperiodic information, but that the circadian phase during which melatonin is present is not. PMID- 1920044 TI - An exploratory study of attitudes, beliefs and practices related to the interim dietary guidelines for reducing cancer in the elderly. AB - In this pilot study, a self-administered questionnaire was used to assess the health attitudes, beliefs and practices related to each of the Interim Dietary Guidelines for Reducing Cancer Risk (I.D.G.R.C.R.) in a convenience sample of elderly Caucasian subjects (N = 30) over 60 years old. The questionnaire items included personal efficacy, perceived motivators and barriers, and current practices related to the compliance of each of the dietary guidelines. The distributions of responses to the questionnaire items show variations in the subjects' attitudes, beliefs and current dietary practices related to each of the dietary guidelines. Most subjects reported current practice of most guidelines except the guideline of a low fat diet. Most of the time, the subjects perceived one or more motivations to comply with the guidelines of eating fruits and vegetables high in vitamin C, and eating dark green or deep yellow vegetables. Taste and health benefits were shown to be important factors among motivators influencing the compliance to the dietary guidelines. The findings of this exploratory study have direct implications for planning nutrition intervention programs for cancer risk reduction in the elderly. PMID- 1920045 TI - Effects of gender, ethnicity and place of residence on nutrient intake among elderly residents of southwestern Louisiana. AB - The purpose of this study was to examine the joint effects of gender, ethnicity, seasonal variations and place of residence on nutrient intake among elderly residents of Southwestern Louisiana. Three hundred and fifty-one elderly subjects volunteered and completed all four interviews evenly spaced throughout the year. Multiple analysis of covariance and hierarchal log linear regression were used to examine the joint effects of the independent variables on nutrient intake of eight nutrients; calories, protein, iron, calcium, vitamin C, vitamin A, riboflavin and thiamin. There were differences between males and females for the intake of calories, protein, iron and vitamin C. Over time, there were differences between rural and urban subjects. Rural subjects showed greater seasonal variability than urban subjects. In addition, the three ethnic groups showed different patterns of seasonal variability. When the nutrient intake data were dichotomized at 68% of the Recommended Dietary Allowances, we found that Blacks were more likely to report values below 68% of the RDA than were either Caucasian group. Also, males were more likely to report values below 68% of the RDA than were females. This study illustrates the need for assessing the effects of multiple factors on nutrient intakes. It also shows that there can be significant differences even between nominally similar ethnic groups. With the increased nutritional risk that the elderly face, further research is needed to clarify and extend these results. PMID- 1920046 TI - Aging and weight control: dietary management of diabetes. AB - Nutritional treatment priorities for elderly patients with diabetes may vary with age, relative body weight, type of diabetes, other health factors and life-style. The age-adjusted tables for recommended body weight have implications for setting weight goals for diabetes treatment and for individuals at risk for developing diabetes. Dietary management of elderly patients with or at high risk for developing diabetes needs to consider: (1) weight changes associated with age, (2) the relative merits of various weight control methods, (3) composition of the recommended diabetic diet, and (4) factors influencing the selection of a therapeutic approach for an individual. PMID- 1920047 TI - Dietary calcium intake and other risk factors: study of the fractured patients in Hong Kong. AB - Osteoporosis has become a major health problem among the elderly in Hong Kong. This study compares the level of dietary calcium intake and the differences in various risk factors among elderly fracture patients and elderly without fractures. Furthermore, this study identifies the relationship between the risk factors and the amount of calcium intake; and classifies the fracture patients and the low calcium intake group. Although the design of the present study precludes testing causal hypotheses, the findings are suggestive of factors that are likely to be important in a program to reduce fractures among elderly populations. PMID- 1920048 TI - Documenting malnutrition--checking how we measure up. PMID- 1920049 TI - The problem with case management. PMID- 1920050 TI - Documentation of discharge teaching before and after use of a discharge teaching tool. AB - Newly diagnosed Type 1 diabetic patients and their parents have a great deal of complex teaching needs before discharge. Documenting the discharge teaching and planning is an important nursing responsibility. The documentation of discharge teaching ensures the highest quality of patient care. With pressures from insurance companies and diagnostic-related groups, nurses must perform extensive discharge teaching in an abbreviated time frame. A Diabetic Discharge Teaching Tool (DDTT) is an instrument that can facilitate concise documentation and assist in developing the plan of care over the ensuing hours or days. PMID- 1920051 TI - Adaptation to chronic illness in childhood: diabetes mellitus. AB - The purpose of this paper is to discuss a conceptual frame of reference for the study of human responses to chronic illness in childhood using diabetes mellitus as a model case and to review the research findings on physiological and psychological adaptation. In addition, the implications of these studies for nursing practice are presented. PMID- 1920052 TI - Patient care plans for intershift report. AB - Inconsistent communication during intershift report had resulted in loss of vital information. This project was developed to implement the use of nursing care plans for intershift report on a 25-bed school-age unit. A review of literature showed an absence of any systematic method for intershift report. Classes that included a 20-minute video, written guidelines, and discussion were used to promote the use of nursing care plans for intershift report. A questionnaire was administered to the nursing staff 3 weeks after class to evaluate the project. The evaluation of use of the care plans indicated: (a) a more focused intershift report; (b) an improved structure for report, including important information about the child and family; (c) increased communication; (d) more practical up-to date care plans; and (e) increased professionalism and collaboration. PMID- 1920053 TI - Feeding the newborn with cleft lip and/or palate: the enlargement, stimulate, swallow, rest (ESSR) method. AB - The failure of newborns with cleft lip and/or cleft palate to properly gain weight remains a frustrating reality for many families regardless of the complex medical technology designed to avoid this problem. The enlargement, stimulate, swallow, suck (ESSR) feeding method was developed to easily and inexpensively reduce the occurrence of poor weight gain among these patients. Families and health care providers will benefit from adopting this method which encourages and provides successful feeding experiences for everyone involved with this group of patients that were once thought of as difficult to feed. PMID- 1920054 TI - Nursing considerations for the neonate awaiting heart transplantation for the hypoplastic left heart syndrome. AB - This article discusses the congenital heart lesion identified as hypoplastic left heart syndrome (HLHS) and the pretransplant management of the neonate born with this defect. Discussion of pretransplant management includes hemodynamic, ventilatory/pharmacological, immunologic, ethical, and economic considerations. An increased knowledge of these early management principles is a necessity, not only for nursing staff working with this population of heart transplant patients, but also for nursing staff in any center that may identify and need to stabilize an infant with this defect. Relevant nursing considerations are presented to assist nurses in supporting the neonate and his or her parents during the time when decisions about heart transplantation must be made. PMID- 1920055 TI - Nursing responsibility in the diagnosis, care, and treatment of the child with gastroesophageal reflux. AB - Gastroesophageal reflux (GER) has been known to occur in infants but was thought to be normal. As a result of increased recognition of GER and a clear documentation of GER with extended (18 to 24 hour) esophageal pH monitoring, several severe complications of GER in children have become apparent. An immature cardiorespiratory system is susceptible to some complications of GER such as apnea, choking, recurrent cough or wheezing, and recurrent aspiration pneumonia. Noncardiorespiratory complications include weight loss, esophagitis, anemia, irritability, posturing, malnutrition, and developmental delays. Nursing assessment contributes to a complete clinical picture and the subsequent treatment choice of the physician. To form an accurate assessment of the child with suspected GER, the nurse must be aware of the symptoms and complications of this condition and must precisely execute diagnostic studies, particularly extended esophageal pH monitoring. Nursing responsibilities also include providing a safe yet stimulating environment for the child, teaching parents to participate in the child's care, supporting parents through hospitalization, and preparing both the parents and child for discharge and follow-up care at home. PMID- 1920056 TI - Hospitalized school-age children express ideas, feelings, and behaviors toward God. AB - Several published studies have reported that children are capable of having a relationship with God. There is little documentation of the influence of stressful situations such as hospitalization on this relationship. Twenty-eight hospitalized subjects (8 to 10 years old) were interviewed using a picture and storytelling technique. Three core processes were identified: how children told a story about a hospitalized child; attributes assigned to God; and responses of children to God in an illness situation. The findings suggest that the child's relationship with God could be helpful in coping with the fears and anxieties normally present during hospitalization. The findings also support those of others who found children can view illness as a punishment from God. PMID- 1920057 TI - The cost to our children: the issue of gun control. PMID- 1920059 TI - Self-nurturance for educators. PMID- 1920058 TI - Safe administration of small-volume enteral feedings: an alternative to intravenous pumps. PMID- 1920060 TI - Pediatric nursing in Israel. PMID- 1920061 TI - Representativeness and conjoint probability. AB - People commonly violate a basic rule of probability, judging a conjunction of events to be more probable than at least 1 of its component events. Many manifestations of this conjunction fallacy have been ascribed to people's reliance on the representativeness heuristic for judging probability. Some conjunction fallacies, however, have been ascribed to the incorrect rules people use to combine probabilities. In 2 experiments, representativeness was pitted against probability combination to determine the contributions of each to the fallacy. Even for exemplar representativeness problems, the fallacy stemmed primarily from the application of incorrect combination rules. Representativeness seemed to be involved only insofar as it influenced the probabilities of a conjunction's component events. Implications of these findings are discussed for the representativeness account of judgmental errors and the relation between similarity and probability. PMID- 1920062 TI - Comparison and expectancy processes in human judgment. AB - This work explored a judgment model proposed by Manis and Paskewitz (1984a). The model suggests that prior experience with the members of a given category affects the assessment of other category members in 2 ways: (a) by providing a basis for comparison and (b) by leading the judge to expect that new exemplars will resemble those previously encountered. In 4 experiments, respondents judged the height of different people on the basis of full-length photographs. The height of the models in an induction series constituted the main independent variable. The effects of contrasting inductions (e.g., short vs. tall women) affected the judges' subsequent assessments in a test series. Both comparison and expectancy processes played a significant role, sometimes opposing one another and sometimes acting in parallel (i.e., supporting one another). PMID- 1920063 TI - Group members' reactions to opinion deviates and conformists at varying degrees of proximity to decision deadline and of environmental noise. AB - Four experiments examined freely interacting groups to investigate the determinants of group members' reactions to opinion deviates and conformists. In the 1st experiment, the deviate was rejected more when he or she articulated the dissenting opinion in close proximity to the group-decision deadline versus at an earlier point in the group discussion. In the 2nd, 3rd, and 4th experiment, the deviate was rejected more when the group discussion was carried out in a noisy versus a quiet environment. Furthermore, when the conformist's contributions to the group's attempts to reach consensus were made salient (in Experiment 4), he or she was evaluated more positively in a noisy versus a quiet environment. The results were discussed in terms of the notion that group members' tendency to denigrate a deviate or extol a conformist may be stronger when their need for collective cognitive closure is heightened. PMID- 1920064 TI - Attachment styles among young adults: a test of a four-category model. AB - A new 4-group model of attachment styles in adulthood is proposed. Four prototypic attachment patterns are defined using combinations of a person's self image (positive or negative) and image of others (positive or negative). In Study 1, an interview was developed to yield continuous and categorical ratings of the 4 attachment styles. Intercorrelations of the attachment ratings were consistent with the proposed model. Attachment ratings were validated by self-report measures of self-concept and interpersonal functioning. Each style was associated with a distinct profile of interpersonal problems, according to both self- and friend-reports. In Study 2, attachment styles within the family of origin and with peers were assessed independently. Results of Study 1 were replicated. The proposed model was shown to be applicable to representations of family relations; Ss' attachment styles with peers were correlated with family attachment ratings. PMID- 1920065 TI - Goal setting and the differential influence of self-regulatory processes on complex decision-making performance. AB - The effects of goal setting and cognitive self-regulatory processes were examined on a highly complex task, a managerial decision-making simulation. It was hypothesized that the presence vs. absence of a specific performance goal would moderate the strength of relations between performance and 2 self-regulatory processes: self-efficacy judgments and self-evaluative reactions. Ss received either a moderately or extremely difficult task goal, or no specific goal. Self regulatory processes were assessed after an initial trial block. Regression analyses revealed that, as predicted, both self-regulatory processes more strongly affected performance when Ss received a specific goal. Contrary to earlier findings obtained with simple activities, dissatisfaction with prior outcomes impaired performance. Ss who were dissatisfied with past attainments exerted much decision effort but adopted inferior task strategies that produced poorer results. PMID- 1920066 TI - The immediate effects of positive and negative feedback signals. AB - Reaction time priming techniques were used in 4 experiments to assess the effects of feedback signals on arousal, response, and attentional processes. The letter A, C, or F served as a priming signal presented 100 ms before a target letter. Emotional value was manipulated by using A, C, and F to reflect good, average, and poor performance on the previous trial. The positive (A), neutral (C), and negative (F) primes did not differ in their effects on arousal. At the response level, positive and neutral primes exerted similar effects, and negative primes led to response inhibition. Regarding attention, positive and negative primes attracted greater attention than neutral primes, with the effect stronger for positive than for negative primes. These effects disappeared when the emotional value of the stimuli was removed, and the effects were not a consequence of expectancies or performance factors extending across trials. PMID- 1920067 TI - Accuracy in social perception: contributions of facial and vocal information. AB - The validity of social perceptions was assessed on the basis of facial or vocal information. Specifically, impressions of stimulus persons' power and warmth were obtained on the basis of either a facial photograph or a voice recording. These were compared with the stimulus persons' self-reports along the same dimensions. Face- and voice-based impressions did predict self-view. The specific facial and vocal characteristics that mediated these links were also considered. Potential mechanisms that may yield the match between self-perceptions and impressions based on nonverbal cues are discussed. PMID- 1920068 TI - Mitraflex: development of an intelligent, spyrosorbent wound dressing. PMID- 1920069 TI - Surface properties and platelet reactivity of segmented poly(etherurethanes) and poly(etherurethaneureas). AB - Segmented poly(etherurethanes) (SPUs) and segmented poly(etherurethaneureas) (SPUUs) with various hard and soft segment components were prepared. The surface characterization of SPUs and SPUUs in the air-equilibrated state and in the hydrated-state was carried out by means of X-ray photoelectron spectroscopic (XPS) and dynamic contact angle measurements. XPS revealed that in the air equilibrated state, lower surface free energy components were enriched at the air solid interface, whereas in the hydrated-state higher surface free energy components were enriched at the water-solid interface. The change in environment from air to water induced the surface reorganization in order to minimize interfacial free energy. The large contact angle hysteresis was observed for SPUs and SPUUs. This hysteresis can be mainly ascribed to the surface reorganization process. Platelet adhesion tests on SPU and SPUU surfaces indicated that the existence of surface microphase separated structure played an important role in the attainment of blood compatibility. PMID- 1920070 TI - Adhesion and stability of blood cells onto polymer substrates: effect of glow discharge. AB - The adhesion of platelets, red blood cells, and lymphocytes onto various polymer substrates, hydrophobic to hydrophilic in nature, has been studied. Cell adhesion is found to be higher on hydrophilic substrates. The stability of these adhered cells has also been studied under a flow rate of 20 ml/min. Further the effect of glow discharge treatment onto various substrates is investigated. It seems the stability is more on glow discharge treated substrates due to increased surface free energy. PMID- 1920071 TI - Bioactive polymers 54. Pharmacological properties of modified neomycin. AB - Modified neomycin prepared by the ionic coupling on xanthan with an activity of 380 UI/mg was characterized in regard to its in vitro and in vivo release rate and therapeutic action with artificial tear eluent. The dynamic system in vitro release showed that after 4 h, there appears a "zero-order" kinetic. Ophthalmic inserts were prepared from modified neomycin and they are used in treating bacterial conjunctivitis. Sterilization of the conjunctival sac is obtained 12 h after insert administration. PMID- 1920072 TI - Titanium-protein interaction: changes with oxide layer thickness. AB - Since titanium is being used for various biomedical applications requiring enhanced blood compatibility, which may be partly due to its extremely stable oxide layer, an attempt is made here to understand the effect of oxide layer thickness on protein adsorption. Different thickness of oxide layers have been coated on titanium foil using anodizing method and thickness of oxide layers deposited have been measured by an ellipsometer. Studies of competitive adsorption of proteins, using I125 labelled protein from a mixture of 25 mg% albumin, 15 mg% gamma-globulin and 7.5 mg% fibrinogen indicate an increased adsorption of proteins onto the oxide layer coated surfaces compared to the bare surface. PMID- 1920073 TI - Community health advisors: a caring presence. PMID- 1920074 TI - A Christian nurse on Capitol Hill. PMID- 1920075 TI - Susan Grosser: transformed to serve. Interview by Melodee Yohe. PMID- 1920076 TI - Martha's gift. PMID- 1920077 TI - Changing the heart of nursing. PMID- 1920078 TI - Just passing through. PMID- 1920079 TI - Nursing's bright future: key leaders speak out on faith and vision. PMID- 1920080 TI - Bringing God's values to nursing. PMID- 1920081 TI - Aeromonas hydrophila: variability in biochemical characteristics of environmental isolates. AB - A total of 161 strains, including 144 aeromonads, of which 100 had been isolated from water and sediment samples from the Chesapeake Bay, five clinical and 33 Anacostia River isolates of Aeromonas hydrophila, six Aeromonas sobria, and ten reference cultures were examined in a numerical taxonomy study in which each of the strains were examined for 56 unit characters. Similarity between strains was computed using the simple matching (SSM) and Jaccard (SJ) coefficients. The strains were clustered by unweighted average linkage and single linkage algorithms. Results of all analyses yielded similar clusterings of strains. Of the 161 strains included in the study, 148 were recovered in seven major clusters. A large cluster of Aeromonas hydrophila yielded two sub-clusters. From the results of the taxonomic analysis it is concluded that several biovars of Aeromonas hydrophila can be isolated from the aquatic environment, but geographical or site specific distribution of the biovars could not be detected. PMID- 1920082 TI - Mechanistic studies of two amino acid racemases of broad substrate specificity from Pseudomonas striata and Aeromonas caviae. AB - The conversion of L-[alpha-2H]alanine in H2O and unlabeled L-alanine in 2H2O into D-alanine, under nearly irreversible conditions, with the amino acid racemase from Pseudomonas striata showed significant internal transfer of the alpha hydrogen. This result has been interpreted as being indicative of a single base mechanism for the racemization. The relative rates of deuterium incorporation into unlabeled D- and L-methionine by the two amino acid racemases of broad substrate specificity from P. striata and Aeromonas caviae, were measured in 2H2O. The results showed a markedly different pattern, dependent upon the configuration of the initial substrate; with D-methionine as substrate deuterium is incorporated into both enantiomers at approximately the same rate, but with L methionine as substrate deuterium is incorporated considerably faster into the D than the L enantiomer. These results argue against a single base mechanism of racemization for these enzymes and are best rationalized in terms of a double base model where only one of the bases undergoes proton (deuterium) exchange with the solvent while the amino acid is enzyme-bound. The interpretation of the earlier experiment needs to be considered in light of these results. PMID- 1920083 TI - Genetic studies of the ends of a locked-in kappa prophage in Serratia marcescens by transductional and vegetative crosses. AB - In temperate phage kappa of Serratia marcescens several special features of different phages are combined. The unessential genes lI, iny, cII and, at least to some extent, even the integrase gene int are not subject to negative control by the repressor, the product of gene cIII. A genetic map of the prophage was established using defective, heat-induced lysates of int- lysogens both in vegetative crosses with sus mutants of essential genes and in transduction of the four unessential genes to lysogenic recipients. Results from reciprocal four factor-crosses concerning the order of the four genes had to be included. The four genes are located near the right end of the prophage, whereas cIII lies near its left end. In vegetative phage all five genes lie in an interval between the essential genes T and U, comprising 10% of kappa's genetic map. The right prophage end appears to face at least two trp cistrons, among them the gene encoding anthranilate synthetase. lI encodes a product that masks the phage receptors in the cell wall. The gene product of iny interferes with the growth of infecting phage y. The natural function of cII is still unknown, but some of its mutants display a cold-sensitive phenotype, their plaques being clear at 30 degrees C and turbid at 37 degrees C. Bacteria with such prophages stop producing viable progeny when the cultures are shifted from 37 degrees C to 30 degrees C. These cold-sensitive mutants are partly dominant and partly recessive. Analysing a virulent mutant, a gene ant encoding an antirepressor was discovered, but so far there is no evidence that it is regulated by an extra repressor. The gene is located relatively near the left prophage end. Evidence is presented that the exogenotes in transduction with the defective lysates continue to exist for some time after a first recombinational event. PMID- 1920084 TI - [Biosynthesis of anthracycline: a new interpretation of the results for daunomycin biosynthesis]. AB - On the basis of literature data and our own experiments the "late" biosynthetic pathway to daunomycin has been interpreted from a new point of view considering both the in vivo biosynthesis and formation of shunt products. In contrast to existing hypotheses proposed by other authors we discuss a modified sequence leading to C-11 oxidation and, as a consequence, understand epsilon-rhodomycinone as a shunt product instead of a biosynthetic intermediate. In addition, a new hypothesis about the "early" steps of the ring formation from polyketides by a sequence of enzyme reactions has been proposed. PMID- 1920085 TI - A three-step approach combining Bayesian regression and NONMEM population analysis: application to midazolam. AB - NONMEM, the only available supported program for population pharmacokinetic analysis, does not provide the analyst with individual subject parameter estimates. As a result, the relationship between pharmacokinetic parameters and demographic factors such as age, gender, and body weight cannot be sought by plotting demographic factors vs. kinetic parameters. To overcome this problem, we devised a three-step approach. In step 1, an initial NONMEM analysis provides the population pharmacokinetic parameters without taking into account the demographic factors. Step 2 consists of individual bayesian regressions using the measured drug concentrations for each subject and the population pharmacokinetic parameters obtained in step 1. The bayesian parameter estimates of the individual subject can be plotted against the demographic factors of interest. From the scatter plots, it can be seen which are the demographic factors that appear to affect the pharmacokinetic parameters. In step 3, the NONMEM analysis is resumed, and the demographic factors found in step 2 are entered into the NONMEM regression model in a stepwise manner. This method was used to analyze the pharmacokinetics of midazolam in 64 subjects from 714 plasma concentrations and 11 demographic factors. CL (elimination clearance) and V1 were found to be a function of body weight. Age and liver disease were found to decrease CL. Of the 11 demographic factors recorded for each patient, none was found to influence VSS or intercompartmental clearance. PMID- 1920087 TI - Optimal extravascular dosing intervals. AB - An explicit formula is presented for simple calculations of the dosing time, tau, that results in a steady-state peak-to-trough ratio of 2 in extravascular dosings. Contrary to other formulae presented, the calculations are guaranteed to be well bound in the percentage error (less than 1%) for any parameter value combination. It is shown that the biexponential dosing interval problem can be transformed into a general, dimensionless problem enabling a global error analysis in the approximation. The proposed formula is demonstrated in the calculation of an "optimal" dosing interval for quinidine. An algorithm and FORTRAN computer program OPTAU for exact calculation of tau and dosing simulations is also demonstrated in the quinidine example. PMID- 1920086 TI - A pharmacokinetic model describing the removal of circulating radiolabeled antibody by extracorporeal immunoadsorption. AB - Extracorporeal immunoadsorption is a new technique for removal of circulating radiolabeled antibody from the peripheral blood (1) to reduce background activity for improved tumor imaging, and (2) to reduce whole-body and marrow toxicity when high doses of radiolabeled antibodies are used for antitumor therapy. A pharmacokinetic model was developed to describe plasma disappearance of 111In-KC 4G3 prior to, during, and after immunoadsorption in humans. The model is developed based on a two-compartment open model, and during immunoadsorption a third compartment is added for removed radioactivity by the immunoadsorption column. Goodness-of-fit statistics indicate a good fit of the model to the data. The resulting pharmacokinetic parameters for a selected patient are V1 = 2.64 L, VSS = 3.64 L, t 1/2 alpha = 3.77 hr, and t 1/2 beta = 48.5 hr. The immunoadsorption clearance (CLIA = 19.3 ml/min) was 21-fold greater than the patient's plasma clearance (CL10 = 0.899 ml/min), indicating a very effective immunoadsorption process. The model predicts an increase in plasma radioactivity upon termination of immunoadsorption, probably due to redistribution of radioactivity from the extravascular compartment to the plasma in response to the rapid decline in plasma radioactivity during immunoadsorption. Two series of simulations were performed to examine the influence of onset time and duration of immunoadsorption. In series one the onset time was varied and in series two immunoadsorption duration was varied. In series one, the predicted radioactivity amounts adsorbed by the immunoadsorption column ranged from 75% of the injected dose (4-hr onset) to 52% of the injected dose (24-hr onset). In series two, immunoadsorbed radioactivity ranged from 32% (2-hr duration) to 64% of the injected dose (12-hr duration). When instituted as early as 4 hr, the predictions suggest that earlier immunoadsorption onset improves the effectiveness of radioactivity removal, relating to higher early circulation concentrations, and longer immunoadsorption periods remove more radioactivity, but also result in larger predicted radioactivity redistribution form tissue to plasma. To employ the immunoadsorption procedure for tumor imaging and therapy optimally, the data and our predictions indicate that a compromise must be made that will balance immunoadsorption onset and duration against tumor radioactivity uptake and subsequent radioactivity redistribution from tissues back to plasma. Together with biologic considerations providing sufficient antigen-antibody interaction and dependent on the utilized radioisotope, these data support the utility of extracorporeal immunoadsorption during the radioimmunodetection of cancer and for future therapeutic applications. PMID- 1920089 TI - Estimating the postantibiotic effect: a two-phase mathematical model. AB - The postantibiotic effect (PAE) is a suppression of bacterial growth that persists after a short exposure to antimicrobials. The active antibiotic delays the resumption of normal growth. This suppression of bacterial growth following antibiotic removal is described by a two-phase model. The quantification of PAE is a function of the model parameters, for which consistent and asymptotically normal estimators are available. PMID- 1920088 TI - Stepwise determination of multicompartment disposition and absorption parameters from extravascular concentration-time data. Application to mesoridazine, flurbiprofen, flunarizine, labetalol, and diazepam. AB - When disposition is monoexponential, extravascular concentration-time (C, t) data yield both disposition and absorption parameters, the latter via the Wagner Nelson method or deconvolution which are equivalent. Classically, when disposition is multiexponential, disposition parameters are obtained from intravenous administration and absorption data are obtained from extravascular C, t data via the Loo-Riegelman or Exact Loo-Riegelman methods or via deconvolution. Thus, in multiexponential disposition one assumes no intrasubject variation in disposition, a hypothesis that has not been proven for most drugs. Based on the classical two- and three-compartment open models with central compartment elimination, and using postabsorptive extravascular C, t data only, we have developed four equations to estimate k10 when disposition is biexponential and two other equations to estimate k10 when disposition is triexponential. The other disposition rate constants are readily obtained without intravenous data. We have analyzed extravascular data of flurbiprofen (12 sets), mesoridazine (20 sets), flunarizine (5 sets), labetalol (9 sets), and diazepam (4 sets). In the case of diazepam intravenous C, t data were also available for analysis. After disposition parameters had been estimated from the extravascular data the Exact Loo-Riegelman method with the Proost modification was applied to the absorptive extravascular data to obtain AT/VP as a function of time. These latter data for each subject and each drug studied were found to be fitted by a function indicating either simple first-order absorption, two consecutive first-order processes, or zero-order absorption. After absorption and disposition parameters had been estimated, for each set of extravascular data analyzed, a reconstruction trend line through the original C, t data was made. The new methods allow testing of the hypothesis of constancy of disposition with any given drug. There is also a need for new methods of analysis since the majority of drugs have no marketed intravenous formulation, hence the classical methods cannot be applied. PMID- 1920090 TI - Necessary modification of formulae estimating the reabsorption rate for drugs subject to enterohepatic recirculation. PMID- 1920091 TI - Area under the curve, bioavailability, and clearance. PMID- 1920092 TI - Dynamic pressure analysis of the diabetic charcot foot. AB - Charcot foot is a form of neuropathic osteoarthropathy, occurring in one or more joints of the foot and ankle. It is a destructive process that alters the weightbearing areas of the foot and, in many cases, results in a rocker-bottom deformity. The authors present quantitative results of dynamic pressure analysis of Charcot foot with the EMED SF pressure analysis system and propose ways in which this information may be used in the evaluation and treatment of this deformity. PMID- 1920093 TI - Treatment of painful diabetic neuropathy with capsaicin 0.075%. AB - An 8-week, double-blind, vehicle-controlled study was conducted to determine the effectiveness of topical capsaicin 0.075% cream in relieving pain associated with diabetic neuropathy. Patients were selected who experienced moderate to very severe pain, which interfered with sleep or activities on a daily basis, and who were unresponsive or intolerant to conventional therapy. The results after 8 weeks showed a statistically significant difference in favor of the capsaicin treated patients, with 90% of these patients improved. The results of this study indicate that topical capsaicin 0.075% cream is safe and effective in managing painful diabetic neuropathy. PMID- 1920094 TI - Electron microscopy of changes in lower extremity muscles in Duchenne muscular dystrophy. AB - Duchenne muscular dystrophy is a genetic disease with a sex-linked pattern of inheritance. This disease is present at birth, becomes symptomatic during early childhood, leads to inability to walk near the end of the first decade, and usually results in death by the end of the second decade. In this study, the extensor digitorum longus and soleus muscles from genetically dystrophic mice were examined at the electron microscopic level. The authors describe their results and discuss how these findings might provide some insight into one of the mechanisms of fiber necrosis in Duchenne muscular dystrophy. PMID- 1920095 TI - Arteriovenous shunting in the patient with diabetic neuropathy. AB - The authors present a review of the literature on arteriovenous shunting, which is a relatively new theory. It is described in the patient with diabetes and coexisting neuropathy. The authors present a case report of a patient with arteriovenous shunting and diabetic neuropathic ulcerations. PMID- 1920096 TI - Diagnosis and treatment of tinea pedis. A review and update. AB - Fungal foot infections are becoming an increasingly common public health problem as the population ages. New studies have shown that some of the traditional therapeutic antifungal agents have multiple actions that enable them to be more efficacious than previously thought, and more efficacious than other agents without multiple actions. In this review article, the pedal infections commonly referred to as tinea pedis, or athlete's foot, are described. The etiologic agents involved in the pathogenesis, the methodologies for proper diagnosis, and the therapeutic agents commercially available for treatment are reviewed. PMID- 1920097 TI - Nail matrixectomies using radio wave technique. AB - The authors present a successful method for surgically correcting ingrown toenails by using radio wave technique. A review of the literature is also presented. PMID- 1920098 TI - Masson's hemangioma of the foot. PMID- 1920099 TI - The myth of running limb varus. AB - Even though the authors believe that there are many flaws in treadmill-based video analysis, they do believe that this study shows that running limb varus is not as important a concept as previously discussed by many authors. The FootTrak system is the first system available to give biomechanical researchers the ability to document the tibia-to-vertical angle with computerized digitation. The clinician with a knowledge of biomechanics understands that functional orthotic devices are more effective on primary calcaneal motions and positions than motions and positions produced by extrinsic tibial, knee, or hip factors. Thus, functional foot orthoses tend to work better in controlling varus during running that is produced by the calcaneus, rather than the tibia. PMID- 1920100 TI - Traumatic osteoarthrosis of the ankle joint secondary to ankle fractures. AB - Arthritis, in one form or another, is one of the most common disorders that affect man. Whether the etiology is systemic, neurologic, or traumatic, the one common finding is the destruction of joint cartilage. Although there have been massive amounts of literature concerning osteoarthritis, little has been written about arthritis of the ankle joint. Current concepts in the pathology, terminology, symptomatology, and treatment of the arthritic ankle are discussed. PMID- 1920101 TI - Guidelines for reconstructing the metatarsal parabola with the shortening osteotomy. AB - Lesser metatarsal pathology is difficult to treat surgically. The shortening osteotomy has shown promise as a useful technique. The following objectives are addressed in this study: 1) to discuss present techniques and two new radiographic measurement systems; 2) to establish mean, standard deviation, and normal range values for these measurement systems; 3) to determine if these measurements vary with foot size; and 4) to use the results to establish general guidelines for metatarsal parabola reconstruction. Means and normal ranges for the various radiographic measurements are identified to help the surgeon with preoperative evaluation and planning. The measurements vary mildly with foot size. PMID- 1920103 TI - Characterization of the performance of shoe insert materials. AB - It has been widely reported that shoe inserts are an effective interventional modality either for the relief of discomfort to the feet associated with a variety of orthopedic disorders or conditions or simply for comfort. Results from many types of experimental tests have been used to obtain the shock absorption capacity of shoe insert materials. The authors contend in this study that, while shock absorption is a highly desirable property, it is by no means the only that should be used to characterize these materials. Thus, a new index of performance of these materials is proposed. This index is computed from data, obtained in a simple experimental test, on both the shock absorption and energy return performances of the insert material. PMID- 1920104 TI - The distal saphenous vein cutdown procedure. AB - Distal saphenous vein cutdown is an excellent method for intravenous access. It allows for a rapid infusion of fluids. Although the saphenous vein cutdown is not commonly performed, the podiatrist should be familiar with this procedure, as it may be necessary during an emergency situation. PMID- 1920102 TI - Orthotic effect on metatarsophalangeal joint extension. A preliminary study. AB - The authors evaluated the effect of modified Root orthoses on first metatarsophalangeal joint extension. Motion within the joint was measured dynamically following the insertion of bone markers into the first metatarsal and the hallux. Extension at the joint was greatest when the subjects were barefoot, the mean angle being 62 degrees. Plimsolls restricted extension of the joint to a mean angle of 57 degrees, while orthoses further reduced the angle of metatarsophalangeal joint extension to a mean angle of 55 degrees. The marginal reduction in first metatarsophalangeal joint extension caused by functional orthoses may be of therapeutic value in the early stages of hallux rigidus, when restricting motion at the joint may slow or prevent development of subchondral sclerosis. PMID- 1920105 TI - Isolated posterior fibular malleolar fracture. Case report and literature review. AB - The authors describe a case involving an isolated posterior fibular malleolar fracture in an 80-year-old female, which was identified on multiple lateral radiographs of the involved ankle and confirmed by computed tomography. The patient was treated conservatively with 10 weeks of walking cast immobilization, resulting in poorly acceptable radiographic and clinical results. The authors review the anatomy of the area of involvement. A literature review, the clinical case study, and a discussion of the difficulty in evaluation of these types of fibular fractures are presented along with a protocol for the diagnosis and treatment of these fractures. PMID- 1920106 TI - TL-61 versus Rohadur orthoses in heel spur syndrome. AB - The authors present the subjective responses of 40 patients with heel spur syndrome or plantar fascitis to orthotic treatment. Twenty patients had Rohadur orthoses and 20 patients had TL-61 orthoses. These data show no difference in the response to or problems created by either TL-61 or Rohadur orthoses. The authors recommend TL-61 as one alternative to Rohadur, now that that latter is unavailable. PMID- 1920107 TI - Madura foot. A case presentation. AB - In this case presentation, the diagnosis was based solely on the histopathologic examination of tissue taken at the time of the first surgery. Subsequent cultures did not reveal any growth of organisms that would cause Madura foot. The patient must be monitored periodically, for it is rare that such an infection is cured with surgery other than amputation. PMID- 1920108 TI - The demographics of an aging revolution. National Council on the Aging, Inc. PMID- 1920109 TI - Fetal alcohol syndrome. PMID- 1920110 TI - Platelet-activating factor induces nonspecific desensitization to bronchodilators in guinea pigs. AB - Platelet-activating factor (PAF) is a potent mediator of inflammation and is a mediator which is known to cause airway hyperresponsiveness in human and experimental animals. However, the mechanism of action of PAF is not clear. In this study we examined the effect of methacholine upon specific airway resistance (SRaw) in guinea pigs and the ability of either isoproterenol or prostaglandin E2 to reverse this effect both before and after PAF administration at sub bronchoactive doses in conscious guinea pigs as well as in isolated airway tissues. SRaw in conscious guinea pigs was monitored using a whole-body plethysmograph. In nonsensitized guinea pigs, a concentration of PAF (0.1 micrograms/ml), which by itself did not affect SRaw, potentiated the methacholine induced increase in SRaw. In ovalbumin-sensitized animals, the response to methacholine was significantly greater as compared to the nonsensitized group. Prior administration of PAF did not potentiate the response to methacholine in ovalbumin-sensitized animals. In isolated tracheal rings and lung parenchymal strips of nonsensitized guinea pigs, preincubation of the tissue with 0.1 microM PAF decreased the sensitivity of isoproterenol to induce relaxation. However, in the ovalbumin-sensitized group of guinea pig tracheas or lung parenchymas, PAF did not reduce further the effect of isoproterenol to elicit relaxation. Furthermore, PAF did not alter the affinity or the density of beta adrenoceptors in guinea pig lung membranes. These data suggest that PAF may potentiate the responses to bronchoconstrictors and desensitize the responses to bronchodilators in a nonspecific manner. This may be a mechanism underlying PAF-induced airway hyperresponsiveness in asthma. PMID- 1920111 TI - Glucagon pharmacodynamics and modulation of sympathetic nerve and norepinephrine induced constrictor responses in the superior mesenteric artery of the cat. AB - The aim of this study was to assess whether the pancreatic peptide glucagon was capable of inhibiting nerve- and norepinephrine-induced vasoconstrictor responses in the superior mesenteric artery of the anesthetized cat. Intra-arterial dose response curves for glucagon and norepinephrine were analyzed by nonlinear regression to estimate the maximal response (maximal dilation, 163%; maximal constriction, 110%) in terms of percent change in superior mesenteric artery conductance and dose of glucagon or norepinephrine required to produce 50% of the maximal response (0.98 and 0.38 micrograms/kg/min, respectively). Constrictor responses (3-min duration) were only weakly inhibited by glucagon. Peak constrictor responses induced by low-dose i.a. infusions of norepinephrine were significantly inhibited (39%) by the high dose of glucagon, whereas the high-dose norepinephrine peak constrictor responses were unaffected by any dose of glucagon. Intermediate and high doses of glucagon significantly inhibited the low frequency (2 Hz) nerve-induced peak constrictions (19% and 34%, respectively). The higher frequency (6 Hz) nerve-induced peak constrictor responses were not significantly affected by glucagon. Vascular escape from nerve- and norepinephrine-induced peak constrictor responses was not related to the degree of initial constriction nor were they affected by glucagon. Glucagon levels produced by our i.a. infusions were estimated to be well outside the pathophysiological range. We conclude that glucagon is not an effective inhibitor of constrictor responses in the superior mesenteric artery and is unlikely to have such an effect at physiological levels. PMID- 1920112 TI - Sympathetic activation by chronic insulin treatment in conscious rats. AB - Normal male Wistar rats pretreated with insulin for 12 days were studied to determine if chronic insulin treatment would reproduce the cardiovascular changes occurring in obese rats with hyperinsulinemia. After 12 days, plasma insulin rose while plasma glucose fell, but basal pressures recorded while the rats were awake remained unchanged. Depressor and tachycardic responses to isoproterenol were enhanced, thereby suggesting that beta adrenergic responsiveness had been increased. By contrast, cardiovascular responses to angiotensin were unaltered. The same rats were then anesthetized with urethane-chloralose, and reflex responses, elicited by elevating blood pressure with phenylephrine or lowering it with sodium nitroprusside, were compared with those from control rats that had not been treated with insulin. Reflex inhibition of splanchnic nerve activity during phenylephrine infusion was weaker, whereas reflex tachycardia during nitroprusside infusion was stronger in insulin-treated rats. However, cardiovascular and sympathetic responses elicited by electrical stimulation of the posterior hypothalamus were the same whether the rats had been treated with insulin or not. Although these differences imply that hyperinsulinemia cannot be solely responsible for the cardiovascular dysfunction in obesity, our results nonetheless suggest that by increasing beta adrenergic responsiveness and reducing sympathetic inhibition, excess insulin can cause sympathetic predominance even without elevating blood pressure. PMID- 1920113 TI - An in vitro evaluation of metabolism and poor membrane permeation impeding intestinal absorption of leucine enkephalin, and methods to increase absorption. AB - The goals of this study were to evaluate how metabolism and poor membrane permeability act as barriers to absorption of a model peptide, leucine enkephalin (YGGFL), and how those barriers can be overcome. The in vitro everted rat intestine method was used. YGGFL was rapidly metabolized when exposed to the mucosa of the jejunum, and destyrosyl leucine enkephalin was formed. Metabolism was slower for ileal intestinal segments, however, and was almost absent when colonic segments were used. The aminopeptidase inhibitor boroleucine, an aminoboronic acid derivative, reduced the YGGFL metabolism rate 2-fold at 1/100th the concentration of substrate when the intestine was simultaneously exposed to substrate and inhibitor. Pretreatment of the intestine with boroleucine further reduced the metabolism rate. Thiorphan, an inhibitor of endopeptidase 24.11, had additive inhibitory effects with boroleucine. Inhibition of metabolism alone did not enable YGGFL to permeate the membrane. The permeability enhancer, sodium glycocholate, also did not alone enable membrane permeation. Substantial YGGFL permeated the membrane only when metabolism was inhibited and permeability was enhanced. EDTA had both these effects. PMID- 1920114 TI - Dehydroabietic acid, a major anionic contaminant of pulp mill effluent, reduces both active p-aminohippurate transport and passive membrane permeability in isolated renal membranes. AB - The renal organic anion transport system plays a pivotal role in elimination of potentially toxic anions. This system is driven by indirect coupling to the sodium gradient at the basolateral membrane, i.e., the organic anion enters the cell in exchange for internal alpha-ketoglutarate (alpha KG) and the in greater than out alpha KG gradient is regenerated by Na+/alpha KG cotransport. The resin acid, dehydroabietic acid (DHAA), is one of several anionic xenobiotics which enter the environment secondary to pulp and paper processing. Because it is largely ionized at neutral pH (pKa, 5.7), DHAA should share the organic anion system. Indeed, Na+/glutarate-coupled p-aminohippurate (PAH) uptake by renal basolateral membrane vesicles was inhibited competitively by DHAA (Ki congruent to 150 microM). Despite the reduced rate of PAH uptake, a substantial, but delayed, overshoot was observed, suggesting additional effects. Passive permeabilities to mannitol, PAH and sodium were all decreased by DHAA, consistent with a general tightening of the membrane. Decreased permeability extended the effective lifetime of imposed ion gradients. Thus, sodium driven glutarate uptake was stimulated by 200 microM DHAA, prolonging and more than doubling its overshoot. Because the immediate driving force for PAH uptake into basolateral membrane vesicles is the magnitude of the glutarate gradient, DHAA increased the driving force for PAH uptake and permitted a substantial overshoot despite the reduced rate of PAH uptake. These data indicate that DHAA has several distinctly different effects on the membrane. PMID- 1920115 TI - On the mechanism of the positive inotropy of low concentrations of strophanthidin. AB - The hypothesis that low concentrations of strophanthidin may decrease contractile force (and intracellular sodium activity, aiNa) under normal conditions but might increase force (while still decreasing aiNa) under conditions of increased Ca load was tested in sheep cardiac Purkinje fibers perfused in vitro. Strophanthidin was used at concentrations (7.5-25 nM, "low strophanthidin") that decreased both force and aiNa in different preparations. A marked reduction in flow rate of Tyrode solution ("ischemia") increases aiNa and increases and eventually decreases force: during ischemia, low strophanthidin decreases aiNa but increases force. High [Ca]o (16.2 mM) and norepinephrine (10 nM) increase force and decrease aiNa: in their presence, low strophanthidin decreases aiNa further but increases force. Caffeine (4 mM) decreases force and increases aiNa, and low strophanthidin increases force while having little effect on the increase of aiNa. In ventricular trabeculae, strophanthidin decreases force under basal conditions but increases force during ischemia or Ca overload. Thus, strophanthidin decreases force by lowering aiNa under normal conditions, but it increases force in spite (and perhaps because) of the decrease in aina under conditions of increased calcium load. PMID- 1920116 TI - Inhibition of airway smooth muscle tone by a phorbol ester in the guinea pig trachea: role of epithelium and receptor reserve of the contractile agent. AB - Bronchial hyperresponsiveness in patients with asthma may be associated with a damaged or dysfunctional epithelium. Also, changes in the activities of protein kinase C have been implicated in the pathogenesis of asthma. This study examined the role of protein kinase C in the modulation of airway smooth muscle tone and the influence of the epithelium on this function. Phorbol-12,13-diacetate (PDA) (10(-8) to 10(-5) M) induced concentration-dependent and epithelium-independent relaxations of guinea pig tracheal rings. PDA (10(-8) to 10(-5) M) induced significantly greater relaxations of tracheal rings contracted with 5 hydroxytryptamine (10(-5) M) than in tissues contracted to an equivalent degree with acetylcholine (10(-6) M). In experiments using phenoxybenzamine (10(-7) M and 10(-5) M), the dissociation constant (KA) for acetylcholine was significantly greater than that for 5-hydroxytryptamine. The fraction of active receptors (q) calculated for acetylcholine was significantly smaller than that calculated for an equieffective concentration of 5-hydroxytryptamine. Relaxations to PDA in tissues contracted with acetylcholine (2 x 10(-6) M) or 5-hydroxytryptamine (10( 5) M) were significantly augmented by phenoxybenzamine (10(-5) M and 10(-7) M, respectively). PDA did not affect contractions to acetylcholine (10(-8) to 10(-3) M) in the presence of epithelium but caused a significant right-ward displacement of the acetylcholine concentration-contraction curve in the absence of epithelium. The concentration-contraction curves for 5-hydroxytryptamine (10(-8) to 10(-5) M) were significantly displaced to the right by PDA in the presence or absence of epithelium. This effect was greater in the absence of epithelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920117 TI - Mechanisms of ionophore-induced stimulation of renin secretion with special reference to a chemiosmotic hypothesis. AB - The effects of several ionophores on renin secretion were investigated in rabbit renal cortical slices. When slices were incubated in the absence of Ca++, the K+ ionophore valinomycin (10(-5) approximately 5 x 10(-4) M) or the monovalent cation ionophore nonactin (10(-4) M) stimulated renin secretion about 2-fold. The renin secretion stimulated by valinomycin was further increased by inclusion of the H+ ionophore, carbonylcyanide m-chlorophenylhydrazone. The electroneutral K+/H+ exchange ionophore nigericin (10(-5) approximately 5 x 10(-4) M) stimulated renin secretion in a dose-dependent manner, producing a maximal stimulation of about 17-fold. Another electroneutral exchange ionophore, monensin, also significantly stimulated secretion. The stimulation by both valinomycin and nigericin was apparent whether slices were incubated in Na(+)-rich or K(+)-rich media. The extent of stimulation by the two ionophores was dependent upon the presence of anion with acetate greater than Cl greater than isethionate greater than thiocyanate. Thiocyanate itself markedly inhibited renin secretion. Incubating of slices in an iso-osmotic ammonium acetate medium which is known to induce rapid swelling of secretory granules, stimulated renin secretion to the magnitude comparable to that of maximal stimulation by nigericin in a potassium acetate medium. The pattern of response to these ionophores indicates that changes in K+, H+ and anion gradients across the renin secretory granule may modulate renin secretory rate. It is proposed that conditions which allow accumulation of K+ and anion within acidic renin secretory granules lead to osmotic swelling of the granules and that granule swelling may promote exocytosis. PMID- 1920118 TI - Inhibition of thromboxane synthetase potentiates the antihypertensive action of an angiotensin-converting enzyme inhibitor by a prostaglandin-dependent but kinin independent mechanism. AB - Mean arterial pressure (BP) was measured in conscious, spontaneously hypertensive rats (SHR). Oral administration of the angiotensin I-converting enzyme inhibitor (ACEI) CGS 16617 significantly lowered BP. In contrast, the thromboxane synthetase inhibitor (TxSI) CGS 12970 lacked an antihypertensive action in SHR. When administered concurrently, the TxSI significantly potentiated the antihypertensive actions of the ACEI. Inhibition of thromboxane synthetase did not potentiate the antihypertensive actions of metoprolol or verapamil, indicating that a specific interaction exists between a TxSI and an ACEI. The antihypertensive actions of CGS 16617 also were potentiated by the cyclooxygenase inhibitor indomethacin, a result suggesting that CGS 12970 may enhance the action of CGS 16617 by inhibiting the action of vasoconstrictor prostaglandins produced after administration of an ACEI. The potentiation of the antihypertensive actions of CGS 16617 by CGS 12970 remained unaffected by either the kallikrein inhibitor aprotinin or a bradykinin receptor antagonist. Thus, although the interaction between an ACEI and a TxSI is a prostaglandin-dependent mechanism, it is not mediated by endogenous kinins. Inhibition of thromboxane synthetase significantly stimulated renin release and significantly attenuated the pressor response to exogenously administered angiotensin II. An increase in the dependency of BP upon the renin-angiotensin system and attenuation of the vascular actions of angiotensin II may serve to explain the potentiation of the antihypertensive action of ACEI after inhibition of thromboxane synthetase. The interaction between ACEI and TxSI was not restricted to SHR, because a TxSI potentiated the actions of an ACEI in both normotensive and deoxycorticosterone acetate/Na hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920119 TI - Effect of morphine administration on rat liver metallothionein and zinc metabolism. AB - The putative involvement of opioid receptors in rat liver metallothionein (MT) regulation has been studied by means of morphine administration. Rat liver MT levels were significantly increased by morphine (10 mg kg-1). This increase was blocked by the opiate antagonist naloxone (4 mg kg-1), suggesting that the effect of morphine on liver MT could involve opioid receptors. The effect of morphine appears to be mediated, at least in part, by glucocorticoids and catecholamines, inasmuch as the administration of specific receptor blockers, RU 486 (100 mg kg 1) for glucocorticoids and labetalol (5 mg kg-1) for catecholamines, diminished liver MT increase induced by morphine. These results identify a potential mediation mechanism for regulating liver MT levels. The putative role of endogenous opioids on liver MT response to stress was also studied by means of opioid receptor blockers. The effect of stress on liver MT levels was not altered by blockade of opioid receptors with either naloxone (4 mg kg-1) or naltrexone (4 mg kg-1) or diprenorphine (4 and 20 mg kg-1), suggesting that endogenous opioids are not involved in MT response to stress. Zn metabolism was also altered by morphine, as morphine administration increased liver cytosolic Zn and decreased serum Zn levels. In contrast to those found in liver MT, these changes were not naloxone-sensitive. The results obtained with RU 486 and labetalol suggest that the effect of morphine on Zn metabolism was mediated in part by glucocorticoids and catecholamines. PMID- 1920120 TI - Membrane-mediated effects of the steroid 17-alpha-estradiol on adrenal catecholamine release. AB - The effects of 17-alpha-estradiol on the secretion of catecholamines from the perfused bovine and cat adrenal gland and bovine chromaffin cells in culture elicited by dimethylphenylpiperazinium (DMPP), methacholine and high potassium were studied. In perfused cat adrenal glands, secretion of catecholamines evoked by pulses of DMPP (1 microM for 30 sec) was decreased by 17-alpha-estradiol at concentrations of 1 and 10 microM by 50 and 80%, respectively. However, secretion evoked by pulses of methacholine (3 microM for 30 sec) was not affected by 1 microM of 17-alpha-estradiol and was affected to a variable extent by 10 microM 17-alpha-estradiol. Catecholamine secretion evoked by higher concentrations of methacholine (100 microM for 60 sec) was reduced by 50% by 10 microM 17-alpha estradiol. 17-alpha-Estradiol decreased secretion evoked by pulses of 120 mM K+ for 10 sec to a similar extent in the perfused bovine and cat adrenal gland. The 45Ca++ uptake into bovine chromaffin cells in culture stimulated by DMPP (100 microM for 10 sec) or high K+ (59 mM for 10 sec) was almost inhibited completely by 100 microM 17-alpha-estradiol. The rapid action precludes a classical genomic mechanism and suggests effects at the cell membrane. PMID- 1920122 TI - Anticonvulsant activity of the low-affinity uncompetitive N-methyl-D- aspartate antagonist (+-)-5-aminocarbonyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10 imine (ADCI): comparison with the structural analogs dizocilpine (MK-801) and carbamazepine. AB - (+-)-5-Aminocarbonyl-10,11-dihydro-5H-dibenzo[a,d] [a,d]cyclohepten-5,10-imine (ADCI), a tricyclic compound structurally related to dizocilpine (MK-801) and carbamazepine, was a potent anticonvulsant in the mouse maximal electroshock seizure test when administered i.p. (ED50, 8.9 mg/kg) or p.o. (ED50, 23.5 mg/kg), but failed to cause motor impairment except at substantially higher doses (TD50 values, 49.2 mg/kg i.p. and 293 mg/kg p.o.). ADCI was also protective against chemically induced seizures in mice, including those produced by 4-aminopyridine (ED50, 7.1 mg/kg s.c.) and pentylenetetrazol (ED50, 37.4 mg/kg s.c.). In addition, ADCI antagonized the behavioral effects and lethality of s.c. administered N-methyl-D-aspartate (NMDA: ED50, 15.2 mg/kg), but was a weaker antagonist of kainate-induced clonic seizures (ED50, 33.0 mg/kg), indicating that the drug is a selective functional NMDA antagonist. In common with other NMDA antagonists, ADCI retarded the development of amygdaloid kindled seizures in rats, but failed to attenuate the afterdischarge duration in fully kindled animals. Whole cell voltage clamp recordings from cultured hippocampal neurons demonstrated that ADCI selectively blocks inward current responses to NMDA in a use-dependent fashion without affecting responses to kainate or quisqualate, indicating that ADCI is a selective open channel (uncompetitive) blocker of the NMDA receptor-ionophore complex. ADCI blocked NMDA-evoked inward current responses with a potency (IC50, 14 microM) similar to that with which it displaces [3H]-1-[1-(2-thienyl)-cyclohexyl]piperidine from binding to NMDA receptor channels in rat brain homogenates (IC50, 11.3 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920121 TI - Behavioral effects of A1- and A2-selective adenosine agonists and antagonists: evidence for synergism and antagonism. AB - The locomotor effects in mice of selective A1 and A2 adenosine agonists, antagonists and combinations of agonists were investigated using a computerized activity monitor. The A2-selective agonist 2-[(2 aminoethylamino)carbonylethylphenylethylamino[-5'-N- ethylcarboxamidoadenosine (APEC), an amine derivative of 2-(carboxyethylphenylethylamino)adenosine-5' carboxamide, was a more potent locomotor depressant than its amide conjugates. The rank order of potency after i.p. injection for adenosine agonists was 5'-N ethylcarboxamidoadenosine (NECA) (ED50, 5.8 nmol/kg) greater than APEC (ED50, 25 nmol/kg) greater than N6-cyclohexyladenosine (CHA) (ED50, 270 nmol/kg). An A1 selective, centrally acting, adenosine antagonist, 8-cyclopentyltheophylline (10 mg/kg), completely reversed the locomotor depressant effects of CHA (A1 selective) and NECA (nonselective) at doses of agonists as high as twice the ED50, and shifted the dose-response curves to the right, suggesting a primary involvement of A1 receptors. 8-cyclopentyltheophylline did not affect the depressant effects of APEC at the ED50, consistent with the A2-selectivity of APEC. The locomotor effects of APEC and CHA were completely reversed by theophylline, but not by the peripherally active 8-p-sulfophenyltheophylline, indicating central action of the adenosine agonists. The depressant effects of APEC, but not of NECA or CHA, were reversed significantly by an A2-selective adenosine receptor antagonist, 4-amino-8-chloro-1-phenyl-[1,2,4]triazol[4,3 a]quinoxaline. Low or subthreshold doses of CHA potentiated the depressant effects of APEC. A subthreshold dose of CHA did not alter the depressant effect of NECA, whereas a subthreshold dose of APEC increased the depressant effects of low doses of NECA. Thus, it appears that A1- and A2-selective adenosine agonists have separate central depressant effects, which can be potentiative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920123 TI - Chemical oxidant potentiates electrically and acetylcholine-induced contraction in rat trachea: possible involvement of cholinesterase inhibition. AB - To determine the roles of oxidants in airway responsiveness, we studied the effects of the chemical oxidant N-chlorosuccinimide (NCS) on the contractile responses to electrical field stimulation (EFS) and acetylcholine (ACh) in isolated rat tracheal smooth muscle segments. Effects of NCS on the contractile response to EFS (5 Hz, 20 sec of duration, 50 V) reached the maximum with a 60 min incubation time. NCS potentiated the contractile response to EFS, with a maximum effect at 3 x 10(-7) M and to ACh, with a maximum effect at 3 x 10(-6) M. Thus, at a concentration of 3 x 10(-6) M, NCS significantly decreased log ED50 concentration of ACh from a control value of -5.56 +/- 0.05 to -6.24 +/- 0.06. Physostigmine (10(-7) M), at a concentration that did not alter resting tension, mimicked NCS-induced effects on contractile responses to ACh and EFS with the greater degree of shift in the respective dose-response curves. However, NCS failed to alter dose-response curves to carbachol. Removal of the epithelium shifted the dose-response curves to ACh to lower concentrations, but NCS showed similar effects on dose-response curves to ACh with and without the epithelium. Active staining showed that both acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) activities were found in the smooth muscle of the rat trachea. NCS inhibited both enzyme activities from rat tracheal homogenates in a concentration-dependent fashion. These results suggest that NCS potentiates cholinergically induced contraction by decreasing cholinesterase activity and that the oxidation of cholinesterase may cause hyperresponsiveness of airway smooth muscle by inhibition of the enzyme activity. PMID- 1920124 TI - Nicotinic pharmacology of anatoxin analogs. I. Side chain structure-activity relationships at peripheral agonist and noncompetitive antagonist sites. AB - Anatoxin analogs were designed to evaluate the importance of H-bonding, planarity, size and steric configuration of the anatoxin side chain moiety with regard to nicotinic potency and efficacy. This report examines the actions of these analogs on the somatic nicotinic acetylcholine receptor at two different loci: the agonist recognition site and the ion channel site. Agonist effects were evaluated using stimulation of contracture and radioligand binding competition for [125I]alpha bungarotoxin sites in Rana pipiens muscle, and stimulation of [3H]perhydrohistrionicotoxin binding and competition for [125I]alpha bungarotoxin sites in Torpedo californica electric organ. Antagonist effects were evident in the inhibition of neurally evoked twitch of the frog sciatic nerve-sartorius muscle preparation and in inhibition of [3H]perhydrohistrionicotoxin binding to Torpedo receptors. The affinity of these analogs for the agonist locus was consistently associated with activation of the AChR. Our results show that side chain steric configuration has an important role in affinity of the (+)-anatoxin a analogs for the nicotinic acetylcholine receptor ion channel sites. Several analogs also revealed stereospecific noncompetitive actions. The (+)-anatoxin-a related structures are important probes for characterizing both agonist and ion channel target sites on the peripheral nicotinic receptor. PMID- 1920125 TI - Differential inhibition of neuropeptide Y on the chronotropic and inotropic responses to sympathetic and parasympathetic stimulation in the isolated, perfused dog atrium. AB - Neuropeptide Y (NPY) inhibits the release of noradrenaline (NA) or acetylcholine (ACh) from nerve terminals in the heart. Thus, we differentiated the blocking effects of NPY on the negative and positive (atrial chronotropic and inotropic) responses to simultaneous stimulation of the intracardiac parasympathetic and sympathetic nerves in isolated, blood-perfused dog atria. NPY (0.1-3 nmol) injected into the sinus node artery decreased atrial contractile force slightly, but not sinus rate by itself. NPY inhibited the negative atrial responses to intracardiac autonomic nerve stimulation in a dose-dependent manner, whereas it rather augmented the positive responses. The inhibition on the negative chronotropic effect was more prolonged than that on the inotropic one. NPY also inhibited the negative responses to intracardiac parasympathetic nerve stimulation alone. However, NPY (3 nmol) did not change the positive responses to intracardiac sympathetic stimulation after atropine was given. NPY did not affect the atrial responses to exogenous ACh or NA. These results suggest that, under activation of autonomic nerves, NPY released from sympathetic nerves attenuates the negative chronotropic and inotropic responses to ACh released from parasympathetic nerves at the prejunctional sites more effectively than the positive responses to NA released from sympathetic nerves, and modifies the sympathetic-parasympathetic interactions in the dog heart. PMID- 1920126 TI - Nicotinic pharmacology of anatoxin analogs. II. Side chain structure-activity relationships at neuronal nicotinic ligand binding sites. AB - Eighteen analogs of (+)-anatoxin-a were evaluated for nicotinic potency at two putative nicotinic acetylcholine receptor sites in the central nervous system. The affinities of the analogs for [3H]nicotine and [125I]alpha-bungarotoxin binding sites were compared. This series of analogs, with modifications to the side chain moieties of the parent structure, enables the importance (for nicotinic binding) of hydrogen bonding strength, planarity, size and steric configuration of this region of the molecule to be assessed. These studies confirm the importance of the side chain stereochemistry and the subordinate role of H-bonding strength of anatoxin analogs. Of all the analogs tested, the parent compound (+)-anatoxin-a is the most potent competitor of ligand binding. Although all analogs have higher affinity at the [3H](-)-nicotine site compared to the alpha-[125I]bungarotoxin site, the rank order of potency is generally the same at both central nervous system sites, and agrees with the order at the muscle nicotinic receptor. However, the simple methoxyamide and the isoxazolidide analogs appear more selective for the neuronal nicotinic receptor subtype identified by [3H](-)-nicotine, indicative of structural differences among the agonist recognition sites. PMID- 1920127 TI - Genotype influences the development of tolerance to nicotine in the mouse. AB - Previous studies have demonstrated that chronic infusion of DBA/2 inbred mice with nicotine results in a dose- and time-dependent tolerance to many of the effects elicited by a challenge dose of nicotine. This tolerance was paralleled by increases in the number of brain nicotinic receptors measured with L [3H]nicotine and alpha-[125I]bungarotoxin binding, suggesting that receptor up regulation may underlie tolerance to nicotine. The studies reported here assessed the development of tolerance to nicotine in five inbred mouse strains that differ markedly in sensitivity to acute doses of nicotine. Mice were infused with nicotine doses ranging between 0 and 6 mg/kg/hr for 10 days and were tested for sensitivity to nicotine using several tests 2 hr after infusion was stopped. Some mouse strains, such as the C57BL/6, developed tolerance to nicotine, as measured by shifts to the right of dose-response curves, at the lowest infusion doses, whereas other strains, such as the C3H/2 and BUB, did not develop measurable tolerance until the highest infusion doses were used. A correlation between sensitivity to acute nicotine treatment and the threshold for tolerance development was observed, suggesting that tolerance develops only after a physiological effect is elicited. All of the mouse strains exhibited a dose dependent increase in nicotine binding in all brain regions; no marked strain differences were seen in up-regulation of this binding site. Chronic nicotine infusion also evoked increases in alpha-bungarotoxin binding, but higher doses were required to elicit this effect. Changes in this binding site were observed after treatment with nicotine doses that elicited tolerance in those mouse strains that are more resistant to an acute dose of nicotine. These results indicate that the relationship between tolerance development and brain nicotinic receptor up-regulation may not be simple. PMID- 1920129 TI - Block of neuronal Ca++ influx by the anti-ischemic agent TA3090. AB - We examined the effect of the novel anti-ischemic drug, TA3090 on Ca++ entry into peripheral and central neurons. TA3090 inhibited voltage-dependent Ca++ entry into rat dorsal root ganglion (DRG) and sympathetic neurons. The degree of inhibition produced by the drug was voltage-dependent. TA3090 also inhibited Ca++ entry into DRG cells elicited by trains of action potentials. TA3090 inhibited Ca++ influx into neurons from the hippocampus. As in peripheral neurons, TA3090 blocked Ca++ influx associated with a Ca++ current in voltage-clamped cells or elicited by trains of action potentials. Furthermore, TA3090 blocked Ca++ influx stimulated by glutamate or N-methyl-D-aspartate. In addition, TA3090 blocked excitatory glutamate-mediated synaptic transmission between hippocampal pyramidal neurons. These data indicate that the protective effects of TA3090 in the brain under ischemic conditions may be partly or completely due to its ability to inhibit neuronal Ca++ influx. PMID- 1920128 TI - Central nervous system effects of acetate: contribution to the central effects of ethanol. AB - Acetate, resulting from ethanol metabolism in the liver, is released into the circulation and is utilized in a number of tissues, including the brain. In its metabolism, acetate leads to the production of adenosine, a powerful physiological mediator. We have investigated the effect of acetate on central nervous system (CNS) function in rodents. Sodium acetate in doses resulting in blood concentrations comparable to those attained after the administration of 1 to 2 g/kg ethanol, had significant CNS effects. Both ethanol and acetate produced a dose-dependent impairment of motor coordination. This effect of acetate was fully blocked by the adenosine receptor blocker 8-phenyltheophylline (8PT), whereas the dose-response relationship for ethanol was shifted to the right by about 30%. The inspired concentration of sevoflurane to achieve anesthesia was significantly reduced by both these agents. General anesthesia was potentiated in a dose-dependent fashion by ethanol and by acetate. The effect of acetate on anesthetic requirements was fully blocked by 8PT. The effect of ethanol on sevoflurane anesthetic requirements was inhibited by 22 to 35% by 8PT. Locomotor activity in mice was reduced by acetate in a dose-dependent fashion, an effect that was also fully blocked by 8PT. On the other hand, ethanol at a dose of 1 to 2 g/kg increased locomotor activity. This likely results from a direct stimulatory effect of ethanol, opposed by an inhibitor effect of acetate. The administration of 8PT enhanced the stimulation of locomotor activity induced by ethanol. In conclusion, acetate, a product of ethanol metabolism has significant CNS effects that can either potentiate or antagonize the effects of the ethanol molecule per se.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920130 TI - Oxygen-induced lung damage in newborn rats, potentiated by 3-methylcholanthrene, a P-450 inducer, and lack of protection by cimetidine, a P-450 inhibitor. AB - Treatment of newborn lambs with the cytochrome P-450 (P-450) inhibitor cimetidine and treatment of adult rats with P-450 inducer 3-methylcholanthrene have been reported to provide protection against oxygen-induced lung damage. Cimetidine (30 or 100 mg/kg/day) and 3-methylcholanthrene (25 mg/kg on days 1 and 2) were tested for their ability to protect newborn rats from the acute and chronic lung disease that follows exposure to 100% oxygen. Half of the rats in each group was exposed to 100% oxygen for 8 days; the other half was maintained in room air. Pulmonary microsomes from 1- to 8-day-old rats contained low levels of total cytochrome P 450 and P-450 IIB1, but undetectable levels of P-450 IA1. Exposure to 100% oxygen and/or treatment with cimetidine had no significant effect on P-450 levels, whereas treatment with 3-methylcholanthrene markedly induced IA1. Survival in 100% oxygen was not affected by cimetidine treatment, but was significantly decreased by 3-methylcholanthrene treatment. At 60 days of age, those rats that survived neonatal exposure to 100% oxygen had elevated right ventricular systolic pressure, increased muscularization of arterioles, and enlarged and irregular alveoli, regardless of the neonatal treatment. These results indicate that 3 methylcholanthrene potentiated the toxic effects of oxygen in newborn rats, in contrast to the protective effect reported for adult rats, whereas cimetidine had no discernable effect on oxygen-induced lung toxicity, in contrast to the protective effect reported for newborn lambs. The induction of cytochrome P-450 IA1 by 3-methylcholanthrene may be important in potentiating the toxic effects of oxygen in the neonatal rat lung. PMID- 1920131 TI - Effects of intra-arterial epinephrine on energy metabolism in exercising rabbit gastrocnemius muscle, studied by in vivo phosphorus nuclear magnetic resonance. AB - Epinephrine has an inotropic effect on skeletal muscle, especially on glycolytic type 2 fibers. The mechanism of this effect is not completely clear and its association with a change in oxidative metabolism or glycolytic activation was not fully investigated. Epinephrine's effects on muscle bioenergetics were studied by in vivo 31P nuclear magnetic resonance to find if mitochondrial metabolism is changed during the inotropic action and if the known glycolytic activation by epinephrine is operative during muscle twitch. The study was also used as a model for the application of in vivo 31P nuclear magnetic resonance in the evaluation of short-term acting drugs. When injected intra-arterially, epinephrine (1 micrograms/kg) augmented the twitch tension of indirectly stimulated, continuously working rabbit gastrocnemius muscle by 15.4 + 6.5%. This increase in work was associated with reduction of phosphocreatine to inorganic phosphate ratio (PCr/Pi) from 3.4 to 2.1 without change in ATP levels. Intracellular pH was reduced from 6.9 to 6.75, but no accumulation of glycolytic intermediates could be observed. The increase in work was not associated with a rise in ADP. All these changes occurred for a few minutes only. The findings suggest that epinephrine's inotropic action is not mediated by a change in mitochondrial metabolism. Glycolytic activation by epinephrine occurs even during twitch and contributes partly to the energy demands of the augmented force. Epinephrine's inotropic effect is, however, not primarily due to changes in bioenergetic kinetics, but to effects on force generating mechanisms, with secondary reduction in energy state. PMID- 1920132 TI - Naloxone causes a dose-dependent increase in total power and delta wave activity in the EEG of opioid-naive rats. AB - We studied the effect of opioid blockade with naloxone on the EEG of rats maintained chronically with i.v. catheters and cortical electrodes. EEG was analyzed on line by fast fourier transform, and drug was given as bolus injections during nighttime, active periods. Naloxone caused increases in EEG amplitude, reflected as increased total spectral power, for 60 to 90 min after injections. Power was increased primarily in the delta bandwidth, but spindles of large amplitude theta activity also occurred. An inverted "U" shaped dose response relationship was obtained, with 1.0 mg/kg being the most effective dose. The appearance of enhanced slow wave activity in the EEG after blockade of opioid receptors suggests that endogenous opioid peptides may play a role in maintaining arousal during active periods in the rat. PMID- 1920133 TI - Pyridine effects on P450IIE1, IIB and IVB expression in rabbit liver: characterization of high- and low-affinity pyridine N-oxygenases. AB - The effects of pyridine exposure on expression of cytochromes P450IIE1, IIB and IVB in rabbit hepatic microsomes and their respective role in pyridine N-oxide production has been examined. Immunoblot analysis revealed that pyridine administration caused a substantial increase in P450IIE1 levels, failed to affect P450IIB content and marginally increased the expression of P450IVB. In an effort to implicate specific forms of P450 in pyridine N-oxide production, the kinetics of pyridine N-oxide formation in uninduced and induced rabbit hepatic microsomal preparations were obtained. Pyridine-induced microsomes exhibited a single low Km value of 81 microM with a approximately 2.5-fold increase in Vmax (2.44 nmol/min/mg protein) relative to uninduced microsomes. Interestingly, pyridine N oxide production in phenobarbital-induced microsomes were also monophasic, exhibiting a single, high Km value of 949 microM and a Vmax of 3.3 nmol/min/mg protein, a approximately 10-fold increase over the uninduced preparations. In contrast, uninduced and isosafrole-induced rabbit hepatic microsomes both exhibited biphasic kinetics; uninduced microsomes gave Km values of 85 and 973 microM, whereas isosafrole-induced microsomes yielded Km values of 229 and 1733 microM, respectively, with a Vmax somewhat less than uninduced microsomes. When kinetic data were normalized for P450 content, a pronounced substrate specificity was detected for both pyridine- and phenobarbital-induced microsomes. para Nitrophenol hydroxylase activity was enhanced approximately 6-fold in pyridine induced microsomes consistent with elevated levels of P450IIE1. para-Nitrophenol competitively inhibited (Ki = 13 microM) the production of pyridine N-oxide in pyridine-induced microsomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920134 TI - NG-monomethyl-L-arginine-induced pressor response at developmental and established stages in spontaneously hypertensive rats. AB - The effect of nitric oxide (NO) pathway inhibitor, NG-monomethyl-L- arginine (L NMMA), on arterial blood pressure was examined in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs) to investigate whether the vasodilating effect of basal levels of NO, one of the endothelium-derived relaxing factors, is preserved during the development of hypertension. L-NMMA (1 100 mg/kg i.v.) produced dose-dependent increase in arterial pressure and bradycardia in anesthetized and conscious SHRs and WKYs. L-Arginine, a precursor of NO, inhibited the pressor response to L-NMMA. The L-NMMA-induced increases in arterial pressure in both 5- to 6- and 12- to 13-week (wk)-old anesthetized SHRs were similar to those of age-matched WKY controls; rather, the increase was significantly larger in 53- to 54-wk-old SHRs than in the age-matched WKYs. In conscious SHRs (13-14 wk-old), L-NMMA induced larger hypertensive effect than in the age-matched WKYs. The amplitude of acetylcholine (ACh)-induced hypotension was somewhat larger in 5- to 6- and 12- to 13-wk-old anesthetized SHRs compared with the age-matched WKY controls. The duration of the hypotension in 5- to 6- and 12- to 13-wk-old anesthetized SHRs was similar to the age-matched WKY controls. L-NMMA significantly reduced the duration of the ACh-induced hypotension; an effect which was recovered by L-arginine. However, L-NMMA did not decrease the amplitude of the hypotension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920135 TI - Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors. AB - DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5 HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920136 TI - Selective transport of an anti-transferrin receptor antibody through the blood brain barrier in vivo. AB - The brain capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo, expresses high concentrations of transferrin receptor, and recent studies show that an antitransferrin receptor monoclonal antibody may function as a BBB drug transport vector. The present report examines the pharmacokinetics of clearance of radiolabeled antitransferrin receptor monoclonal antibody from the bloodstream in rats in vivo, and also assesses the extent to which brain selectively extracts the antibody from the blood compared to other peripheral organs such as liver, kidney, myocardium, or lung. [125I]Mouse immunoglobulin G2a control antibody was cleared monoexponentially with a half-time of 9.8 +/- 2.3 h. The clearance of the [3H]OX-26 antitransferrin receptor antibody from blood was biexponential with half-times of 2.2 +/- 0.8 min (61 +/- 10% of clearance) and 3.9 +/- 0.2 h (39 +/- 4% of clearance). The OX-26 antibody was rapidly taken up by liver during the first 60 min after injection, but this uptake reached rapid saturation, and hepatic OX-26 content actually declined subsequent to the first hour after injection. In contrast, brain continuously extracted the OX-26 antibody from the bloodstream, and the brain volume of distribution of OX-26 reached a value 18-fold greater than the volume of distribution of the mouse immunoglobulin G2a at 5 h after injection. There was no specific uptake of the OX 26 by myocardium or lung, and minor uptake by kidney was observed that also reached saturation within the first 60 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920137 TI - Role of endothelium in responses of isolated hepatic vessels to vasoactive agents. AB - The role of the endothelium as a participant in the responses to vasoactive agents was evaluated in isolated canine hepatic artery (HA) and portal vein (PV) rings. Endothelial and smooth muscle integrity was determined by pharmacologic responses as well as by histologic examination. Smooth muscle relaxation was expressed as the percent of decrease of norepinephrine-induced isometric contraction. Acetylcholine (ACh)-induced relaxation of the HA was abolished by removing the endothelium or by the addition of either hemoglobin, methylene blue (MB) or Ng-mono-methyl-L-arginine. In addition, relaxation induced by nitroglycerin, but not that induced by prostaglandin E1, was attenuated by MB. These data suggest endothelium-dependency of the relaxation to ACh and mediation of the response by endothelium-derived relaxing factor through activation of guanylate cyclase. In contrast, ACh produced contraction of the PV which was unaffected by removing the endothelium. The calcium ionophore, A23187, on the other hand, produced relaxation of the PV, which was significantly decreased by removing the endothelium. Relaxation of both HA and PV, produced by 2 chloroadenosine (2-C-Ado) was partially attenuated by removing the endothelium. With the endothelium intact, neither hemoglobin, MB, Ng-monomethyl-L-arginine nor indomethacin affected the responses to 2-C-Ado in the HA and PV, suggesting that the responses were not mediated by endothelium-derived relaxing factor or products of guanylate cyclase or cyclooxygenase activity. Nitroglycerin relaxed both vessels in the presence or absence of endothelium, indicating that removal of the endothelium had not affected smooth muscle function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920139 TI - Challenges and choices. PMID- 1920138 TI - Effect of potassium channel blockade on the anti-ischemic actions of mechanistically diverse agents. AB - The ATP-sensitive potassium channel opener, cromakalim, protects ischemic hearts and its effect can be reversed by glyburide. It is presently unknown if glyburide can abolish the anti-ischemic effects of mechanistically different agents or if blockers of other potassium channels can abolish the protective effects of cromakalim. Thus, the effect of glyburide on previously reported cardioprotective agents was tested in globally ischemic/reperfused isolated rat hearts. Calcium antagonists, sodium channel blockers and calmodulin antagonists were found to significantly improve postischemic contractile function and reduce lactate dehydrogenase release after 25 min of global ischemia and 30 min of reperfusion. Glyburide did not reverse their cardioprotective effects. 5-(N,N dimethyl)amiloride, an inhibitor of Na+/H+ exchange, significantly reduced lactatedehydrogenase release without improving postischemic contractile function, and glyburide did not reverse this. The potassium channel opener, cromakalim, protected ischemic rat hearts (improved recovery of contractile function and reduced enzyme release) and this was abolished by glyburide. Charybdotoxin blocks both calcium-activated potassium channels and voltage-gated potassium channels and E-4031 the delayed rectifier potassium channels. Neither was found to effect the action of the potassium channel opener, cromakalim. These data indicate that glyburide is selective in that it only blocks the anti-ischemic effects of potassium channel openers and not other cardioprotective compounds. In addition, cromakalim is unaffected by blockers of other potassium channels, further indicating selectivity of glyburide for ATP-sensitive potassium channels. PMID- 1920140 TI - Leadership versus management: a matter of focus. AB - The manager's role is changing due to the changes in the environment. The major change in this role is a move from process management to ensuring outcomes. Assisting staff to achieve outcomes in a constantly changing environment may now be the major contribution of the manager. Five ideas are presented to assist the manager make a successful transition to the role of leader-manager. PMID- 1920141 TI - Heroism: making a difference. PMID- 1920142 TI - Efficient expression of the Paramecium calmodulin gene in Escherichia coli after four TAA-to-CAA changes through a series of polymerase chain reactions. AB - We have expressed the Paramecium calmodulin gene in Escherichia coli by changing the four TAA codons in this gene to CAAs. This was carried out by three polymerase chain reactions (PCRs) and then cloning the product into the expression vector pKK223-3 immediately downstream of its trp-lac hybrid promoter. JM109 strain of E. coli, transformed with the recombinant plasmid harboring the altered Paramecium calmodulin gene, produces a protein judged to be calmodulin. It is recognized by a monoclonal antibody to Paramecium calmodulin; it migrates with the native protein at nearly the same rate in electrophoreses; and it shows a Ca(2+)-dependent shift in electrophoretic pattern. The production of calmodulin is about 170 times as efficient with E. coli as with Paramecium in terms of unit volume of packed cells, and is about 400 times as efficient in unit volume of liquid culture. This method appears useful in site-directed mutageneses and in the heterologous productions of other ciliate proteins. A critique of this method is provided. A calmodulin half-molecule, a by-product of this project, is described. PMID- 1920143 TI - Sphaerospora epinepheli n. sp. (Myxosporea: Sphaerosporidae) observed in grouper (Epinephelus malabaricus). AB - Sphaerospora epinepheli n. sp. is described from grouper, Epinephelus malabaricus, in cage-cultured and wild fish collected from both coastal lines of southern Thailand. Subspherical to spherical spores and mono- or disporous pseudoplasmodia were observed in the lumen of kidney tubules. Pseudoplasmodia were round to elongate, size range 15.6-22.9 microns (length) x 8.4-21.6 microns (width). Spores were 7.8-10.0 microns (length) x 12.3-14.5 microns (thickness), and 7.0-9.5 microns (width) with two spherical polar capsules of equal size measuring 2.9-4.4 microns in diameter and containing polar filaments with six or seven windings. Two uninucleate sporoplasms showed iodine vacuoles. Blood stages, similar to C-blood protozoans observed from freshwater fish in Europe, were found from peripheral blood smears of grouper. Ultrastructural studies of blood stages showed a similar structure to unidentified mobile protozoans from the blood of carp. Electron dense bodies were observed in the cytoplasm of the primary cell blood stages. Infected proximal-tubular epithelial cells showed highly vacuolated cytoplasm and pycnotic nuclei. PMID- 1920144 TI - A soluble phospholipase of Toxoplasma gondii associated with host cell penetration. AB - We previously reported that phospholipase increases host cell penetration by Toxoplasma gondii. Here we show that calcium-dependent phospholipase A (PLA) activity is found in the supernatant of sonically disrupted T. gondii. When fractions of disrupted T. gondii were incubated with host cells, the release of fatty acids and lysolipids was detected. Fractions of sonically disrupted T. gondii with PLA activity increased T. gondii host cell penetration in a bioassay. In addition, a protein of approximately 20 kDa was detected by immunoblot of T. gondii antigens with horse antiserum to snake venom, the major antibody of which recognizes PLA2. Incubation of T. gondii with exogenous PLA2 resulted in increased solubility of a rhoptry protein. This protein, which we previously characterized as involved with enhanced parasite invasion of host cells and which is recognized by monoclonal antibody Tg49, was detected in increased amounts in supernatant fractions of extracellular parasites treated with PLA2. Whereas without PLA2 treatment, it is only slightly soluble under physiological conditions. This raises the possibility that PLA may be implicated in the release of rhoptry proteins. PMID- 1920145 TI - Characterization of the extracellular ribonuclease of Tetrahymena pyriformis W. AB - Several investigations have indicated that Tetrahymena pyriformis secretes ribonuclease activity into culture media. The extracellular ribonuclease from strain W has been purified and partially characterized. The molecular weight was determined by gel filtration to be 26,500. The amino acid composition of the enzyme was compared with those of the three intracellular ribonucleases characterized by Trangas, and substantial differences were demonstrated. The extracellular enzyme hydrolyzed both polyadenylic and polyuridylic acids, indicating lack of absolute base specificity. The hydrolysis of polyadenylic acid followed normal Michaelis-Menten kinetics, but substrate inhibition occurred at high concentrations of polyuridylic acid. The hydrolysis of polyuridylic acid was competitively inhibited by 2'- and 3'-cytidine, guanine, and uridine nucleotides, and by 2'AMP. No inhibition of the hydrolysis of Torula yeast RNA was detected. The kinetic properties of the extracellular ribonuclease are compared with those of the intracellular enzymes. PMID- 1920146 TI - Enhanced uptake and metabolism of riboflavin in erythrocytes infected with Plasmodium falciparum. AB - Riboflavin deficiency inhibits the growth of malaria parasites both in vitro and in vivo in infected animals and humans. Although the precise mechanisms underlying this inhibition are unknown, they may involve enhanced requirements for riboflavin by parasites. To investigate this possibility, the rate of uptake of [14C]riboflavin and the biosynthesis of FMN and FAD from riboflavin were studied in infected (5-8% parasitemia) and uninfected human erythrocytes. All cells were incubated for 0-3 h at 37 degrees C in phosphate buffered saline containing MgCl2, glucose, and [14C]riboflavin (2.5-7.5 microM). At hourly intervals, samples were removed, centrifuged, washed twice with cold buffer, and lysed before counting the radioactivity. The rate of in vitro biosynthesis of FMN and FAD from riboflavin in erythrocytes was measured by ion exchange chromatography and reverse isotope dilution techniques. Results showed that the rate of riboflavin uptake and the biosynthesis of FMN and FAD were enhanced in erythrocytes with parasitemia as compared with results in unparasitized erythrocytes. Riboflavin uptake in erythrocytes was proportional to the extent of parasitemia and especially to percent of schizonts present in erythrocytes. These studies indicate that the requirement for riboflavin may be greater in the parasite than in the host erythrocyte. This increased riboflavin requirement may be due to rapid multiplication, higher metabolic rate, and extreme vulnerability to oxidative stress of malaria parasites compared with that of host erythrocytes. The differential requirement of riboflavin by the host and the malaria parasite may hold important potential for developing new strategies for malaria chemotherapy. PMID- 1920147 TI - Infraciliature, morphogenesis and life cycle of Endosphaera terebrans (Suctoria, Tokophridae). AB - The morphology, infraciliature, and life cycle of Endosphaera terebrans, a suctorian endocommensal of peritrichs, have been studied with the aid of silver impregnation. The life cycle of Endosphaera terebrans begins with infection of the host cell by a small larva. The swarmer has a pointed needle-like cellular projection and two rings of cilia. The swarmer penetrates the the peritrich, loses the cilia, and then matures into an adult. The infraciliature of the adult form has four rows of barren kinetosomes that lack kinetodesmal fibers. By endogenous budding, a migratory larva is produced that leaves the host cell through the peristomial disc and that can infect other peritrichs. PMID- 1920148 TI - Herpetomonas roitmani (Fiorini et al., 1989) n. comb.: a trypanosomatid with a bacterium-like endosymbiont in the cytoplasm. AB - The trypanosomatid previously described as Crithidia roitmani is characterized here at the ultrastructural and biochemical levels. The data indicates that the parasite belongs to the Herpetomonas genus, and we therefore suggest the flagellate to be denominated as Herpetomonas roitmani n. comb. Cladistic analysis of isoenzyme data generated by eight different enzymes showed that the parasite presented a distinct banding pattern and could be grouped with some Herpetomonas spp., but not with Crithidia spp., used as reference strains. Accordingly, when the parasites were grown for longer periods in Roitman's defined medium, expontaneous differentiation from promastigotes to opisthomastigotes (typical of the Herpetomonas genus) occurred. Transmission electron microscopy revealed the presence of bacterium-like endosymbionts in the cytoplasm of all evolutive forms of the parasite. All morphological alterations characteristic of endosymbiont bearing trypanosomatids could be observed. PMID- 1920149 TI - Small GTP-binding proteins associated with secretory vesicles of Paramecium. AB - GTP-binding proteins act as molecular switches in a variety of membrane associated processes, including secretion. One group of GTP-binding proteins, 20 30 kDa, is related to the product of the ras proto-oncogene. In Saccharomyces cerevisiae, ras-like GTP-binding proteins regulate vesicular traffic in secretion. The ciliate protist Paramecium tetraurelia contains secretory vesicles (trichocysts) whose protein contents are released by regulated exocytosis. Using [alpha-32P]GTP and an on-blot assay for GTP-binding, we detected at least seven GTP-binding proteins of low molecular mass (22-31 kDa) in extracts of Paramecium tetraurelia. Subcellular fractions contained characteristic subsets of these seven; cilia were enriched for the smallest (22 kDa). The pattern of GTP-binding proteins was altered in two mutants defective in the formation or discharge of trichocysts. Trichocysts isolated with their surrounding membranes intact contained two minor GTP-binding proteins (23.5 and 29 kDa) and one major GTP binding protein (23 kDa) that were absent from demembranated trichocysts. This differential localization of GTP-binding proteins suggests functional specialization of specific GTP-binding proteins in ciliary motility and exocytosis. PMID- 1920151 TI - Axenic cultivation of the anaerobic free-living ciliate Trimyema compressum. AB - The strain N of Trimyema compressum, an anaerobic free-living ciliate, was cultivated axenically in a medium containing a buffered salt solution, yeast extract, trypticase, and glutathione. Dead bacteria were indispensable as food; a culture of the ciliate together with heat-killed Klebsiella pneumoniae has been established for more than one year. In the medium described, the ciliates grow to a higher cell density than in cultures with living bacteria as food. During the process of axenization, a nonmethanogenic bacterial endosymbiont was lost. In the microbodies of T. compressum, hydrogenase could be localized by the technique of indirect immunofluorescence. PMID- 1920150 TI - Fine structure of a new human microsporidian, Encephalitozoon hellem, in culture. AB - Encephalitozoon hellem is a new human microsporidian isolated from corneal biopsies and conjunctival scrapings of three AIDS patients and cultured in Madin Darby canine kidney (MDCK) cells. Encephalitozoon hellem and Encephalitozoon cuniculi display different protein profiles with sodium dodecyl sulfate polyacrylamide gel electrophoresis and unique antibody binding patterns with murine antisera against Western blots of each organism. Developmental stages of E. hellem in culture are similar to E. cuniculi. Meronts are 1.3-2.7 microns in diameter, develop within a parasitophorous vacuole adjacent to the vacuolar membrane, divide by binary fission, and contain one or two discrete nuclei. Sporonts measure 2 x 3 microns, separate from the vacuolar membrane, and have a thickened outer membrane. Sporoblasts display a tri-layered wall and possess the earliest recognized polar filaments. Mature spores measure 1 x 1.5 microns and are more electron-dense than other stages. Each spore contains a single nucleus, a polar tubule with four to nine coils, thin electron-dense exospore and thick, electron-lucent endospore. Although E. hellem and E. cuniculi differ biochemically and immunologically, their fine structure and development are indistinguishable. PMID- 1920152 TI - Structural alteration of the plasma membrane in spores of the microsporidium Nosema algerae on germination. AB - The fine structure of the plasma membrane in spores of the microsporidium Nosema algerae, a pathogen of mosquitoes, was examined in the resting condition and after the spores were stimulated to germinate in vitro. Slow penetration of resin caused collapse of the germinated spores. Thin sections of germinated spores showed peculiar membrane infoldings that were never found in ungerminated samples. Analogous germination-dependent configurations of the plasma membrane were observed in freeze-fractured preparations of spores either fixed and impregnated with glycerol prior to freezing, or rapidly frozen with liquid propane while in the process of germination. In every case, the replicas presented germinated spores with indentations in the protoplasmic face of the plasma membrane, and apparently complementary blunt spines on the external face, that were absent in ungerminated spores. It suggests that these alterations of the plasma membrane result from a structural adjustment to a spontaneous contraction of the spore case after germination. We discuss this interpretation with regard to conflicting views on the nature of such morphological features. PMID- 1920153 TI - The patterning of ciliates. AB - This past-presidential address considers the relationship between small-scale assembly and large-scale patterning in ciliates. Certain model examples of assembly-based patterning are reviewed, followed by the introduction of Williams and Honts' concept of "meta-assembly" as applied to the development of the oral apparatus. The major part of this review then explores two topics: the nature and origin of large-scale circumferential order, and the manner by which the large scale order of cell directions influences the organization of membranelles of the oral apparatus. In this review, I summarize an existing formal description of large-scale positional order, allude to a more precise abstract theoretical model, and end with a brief discussion of the problem of searching for molecular mechanisms. PMID- 1920154 TI - Sex pheromone perception in male pine sawflies, Neodiprion sertifer (Hymenoptera; Diprionidae). AB - Electroantennographic and single sensillum recordings were performed on male pine sawfly, Neodiprion sertifer, antennae. Responses to the sex pheromone component (2S, 3S, 7S)- 3,7-dimethyl-2-pentadecenyl (diprionyl) acetate (SSS:OAc), to the behavioral inhibitor (2S, 3R, 7R)-diprionyl acetate (SRR:OAc), to the six other enantiomers of diprionyl acetate, and to the biosynthetic precursor diprionol were recorded. Responses to trans-perillenal, a monoterpene identified in female gland extracts and to (2S, 3S, 7S)-diprionyl propionate (SSS:OPr), a field attractant for N. sertifer and some related sawfly species were also recorded. EAG recordings demonstrated a high antennal sensitivity to SSS:OAc and to SSS:OPr. A somewhat lower response was elicited by SRR:OAc. Single sensillum recordings revealed 8-12 different cells firing in each sensillum, corresponding to the number of cells observed in earlier morphological investigations. Out of these cells all, except one, responded to SSS:OAc and to SSS:OPr. No differences in the response to the two components could be observed. The largest amplitude cell in each sensillum was specifically tuned to the behavioral antagonist, SRR:OAc. The pheromone perception system encountered in male pine sawflies thus differs clearly from that observed in moths. PMID- 1920155 TI - Functional and morphological evidence for the existence of neurites from abdominal ganglion bag cell neurons in the head-ring ganglia of Aplysia. AB - Three lines of evidence are presented indicating that axons of the Aplysia neuroendocrine bag cells extend into the head-ring ganglia of the CNS. When the abdominal ganglion was bisected longitudinally, separating the two bag cell clusters, an afterdischarge induced in one cluster generated an afterdischarge in the other via activity through the head-ring ganglia to which each half abdominal ganglion was attached by connective nerves. This suggests that some axons of bag cells in each cluster communicate through the head-ring ganglia. Retrograde labelling of bag cells occurred when rhodamine-conjugated latex microspheres were injected into the cerebral or either pleural ganglion, a direct demonstration that bag cell axons extend into these ganglia. Finally, cell LP1 in the left pleural ganglion was inhibited during a bag cell afterdischarge, an action mimicked by application of alpha-bag cell peptide (alpha BCP). Since alpha BCP can act only close to its site of release due to susceptibility to peptidase activity, it is likely that LP1 inhibition is dependent on the local release of alpha BCP from bag cell neurites in the pleural ganglion. These results open new possibilities for how bag cell afterdischarges may be initiated and broaden the distribution of their effects. PMID- 1920156 TI - Anatomy and physiology of identified wind-sensitive local interneurons in the cricket cercal sensory system. AB - 1. A group of wind sensitive local interneurons (9DL Interneurons) in the terminal abdominal ganglion of the cricket Acheta domesticus were identified and studied using intracellular staining and recording techniques. 2. The 9DL interneurons had apparent resting potentials ranging from -38 mV to -45 mV. At this membrane potential, these cells produced graded responses to wind stimuli; action potentials were never observed at these resting potentials. However, when the 9DL interneurons were hyperpolarized to a membrane potential of approximately -60 mV, a single action potential at the leading edge of the wind stimulus response was sometimes observed. 3. The wind stimulus threshold of the 9DL interneurons to the types of stimuli used in these studies was approximately 0.01 cm/s. Above this threshold, the excitatory responses increased logarithmically with increasing peak wind velocity up to approximately 0.5 cm/s. 4. The 9DL interneurons were directionally sensitive; their response amplitudes varied with wind stimulus orientation. 9DL1 cells responded maximally when stimulated with wind directed at the front of the animal. The apparent peak in directional sensitivity of the 9DL2 interneurons varied between the side and the rear of the animal, depending upon the site of electrode penetration within the cell's dendritic arbor. 5. The locations of dendritic branches of the 9DL interneurons within the afferent map of wind direction were used to predict the excitatory receptive field of these interneurons. PMID- 1920157 TI - An opsin-based photopigment mediates phase shifts of the Bulla circadian pacemaker. AB - 1. The spectral response of the circadian pacemaker of the eye of the mollusk Bulla gouldiana was examined in two ways: by using the latency of the first light evoked compound action potential (CAP) as an acute photoresponse of the putative pacemaker cells of the eye, the basal retinal neurons (BRNs), and by measuring the effectiveness of monochromatic light pulses at resetting the pacemaker. 2. Through measurements of the spectral sensitivity of the acute response of the BRNs, a photopigment absorbing maximally near 490 nm (lambda max) was described. Action spectra of the acute response following isolation of the BRNs, by surgical removal of the distal photoreceptor layer or the use of low Ca2+ media to block chemical synapses on the BRNs, further suggested that a 490 nm lambda max photopigment is used in generating the acute light response. The spectral sensitivity of eyes adapted to a dim background illumination also agreed with the expected absorption of a 490 lambda max rhodopsin. 3. The effectiveness of monochromatic light pulses at shifting the phase of the circadian rhythm in CAP frequency suggested that the photopigment used in the entrainment of the pacemaker is the opsin based molecule identified through acute response measurements. PMID- 1920158 TI - Arctiid moth clicks can degrade the accuracy of range difference discrimination in echolocating big brown bats, Eptesicus fuscus. AB - Four big brown bats (Eptesicus fuscus) born and raised in captivity were trained using the Yes/No psychophysical method to report whether a virtual sonar target was at a standard distance or not. At threshold bats were able to detect a minimum range difference of 6 mm (a delta t of 36 microseconds). Following threshold determinations, a click burst 1.8 ms long containing 5 pulses from the ruby tiger moth, Phragmatobia fuliginosa (Arctiidae), was presented randomly after each phantom echo. The sound energy of the click burst was -4 dB relative to that of the phantom echo. Clicks presented for the very first time could startle naive bats to different degrees depending on the individual. The bats' performance deteriorated by as much as 4000% when the click burst started within a window of about 1.5 ms before the phantom echo. Even when one of ten phantom echoes was preceded by a click burst, the range difference discrimination worsened by 200%. Hence, clicks falling within the 1.5 ms time window seem to interfere with the bat's neural timing mechanism. The clicks of arctiid moths appear to serve 3 functions: they can startle naive bats, interfere with range difference determinations, or they can signal the moth's distastefulness, as shown in earlier studies. PMID- 1920159 TI - Ongoing ultradian activity rhythms in the common vole, Microtus arvalis, during deprivations of food, water and rest. AB - The timing mechanism underlying ultradian (2-3 h) activity patterns in the common vole, Microtus arvalis, was studied using behavioral deprivation experiments. These were aimed at distinguishing between a homeostatic control mechanism, in which the rhythmic behaviour itself is part of the causal loop, and a clock mechanism, independent of the behaviour. In 175 experiments, deprivation of food during 3 ultradian cycles in (subjective) daytime did not result in significant changes in the ultradian periodicity of attempts to obtain the food, compared with ad lib, access to food and water. A minor, but significant increase in ultradian activity time (alpha') occurred in the course of the deprivation, but this was compensated by a shorter ultradian rest (rho'). These results were obtained both in intact animals (n = 24), which showed ultradian and circadian rhythmicity in behaviour, and in animals (n = 21) with electrolytic lesions aimed at the suprachiasmatic nuclei (SCN), which lacked the circadian modulation of behaviour. Simultaneous deprivation of water and food in 8 voles without circadian rhythmicity during 40 experiments also did not lead to any change in the ultradian periodicity of feeding attempts. Rest deprivation was studied in 5 SCN lesioned voles, by forcing running wheel activity to continue following spontaneous running. Thus, the experimental activity bout alpha' was artificially lengthened to 2-9 h in 67 experiments. The onset of the subsequent rest episodes occurred independent of the duration of the preceding alpha'. The duration of rho' was dependent on the preceding, experimental alpha' in a periodic fashion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920160 TI - Cold prevents the light induced inactivation of pineal N-acetyltransferase in the Djungarian hamster, Phodopus sungorus. AB - In the Djungarian hamster seasonal acclimatization is primarily controlled by photoperiod, but exposure to low ambient temperature amplifies the intensity and duration of short day-induced winter adaptations. The aim of this study was to test, whether the pineal gland is involved in integrating both environmental cues. Exposure of hamsters to cold (0 degrees C) reduces the sensitivity of the pineal gland to light at night and prevents inactivation of N-acetyltransferase (NAT). The parallel time course of NAT activity and plasma norepinephrine content suggests that circulating catecholamines may stimulate melatonin synthesis under cold load. PMID- 1920161 TI - The vasopressin-like immunoreactive (VPLI) neurons of the locust, Locusta migratoria. II. Physiology. AB - The two vasopressin-like immunoreactive (VPLI) neurons of the locust, Locusta migratoria, have cell bodies in the suboesophageal ganglion and extensive arborizations throughout the CNS. One of the two peptides responsible for AVP like immunoreactivity is a vasopressin-related peptide with putative 'diuretic hormone' properties. These neurons also have FLRF-like immunoreactivity, probably due to the FMRF-amide-related peptide. SchistoFLRF-amide, isolated from Schistocerca gregaria. This peptide has cardioinhibitory activity and a dual potentiation/inhibition of slow motoneuron induced muscle-twitch tension. Although haemolymph AVP-like peptide titre fluctuates under various conditions, the mechanism that regulates neurohaemal release of this peptide is not understood. Very little is known of the release of SchistoFLRF-amide. We have used intracellular recording from VPLI neurons in vivo to reveal synaptic inputs that lead to changes in their level of spiking activity, and probably, release of both the AVP-like peptides and SchistoFLRF-amide. This pair of neurosecretory cells has a major, common excitatory input whose sustained rate of activity is inversely related to light intensity; VPLI spiking activity, driven by this input, is greater in the dark than in light. This input is from a pair of descending brain interneurons. Their light-sensitivity persists after ablation of compound eyes, optic lobes and ocelli, showing them to be part of an extra-ocular photoreceptor system. Attempts to record from, and individually stain, the descending neuron have been unsuccessful, although its axon location and diameter in the circumoesophageal connective have been determined. Possible locations for its cell body have been identified; one region, close to the pars intercerebralis, is known to be photosensitive in some insects. Mechanosensory stimuli also lead to brief increases in VPLI spiking activity via the descending interneuron, though this modality rapidly habituates. We detect no changes in VPLI spiking activity that consistently correlate with the osmolality of perfusion salines; such changes might have been expected from their previously proposed role in water homeostasis. Alternative roles for VPLI cells are discussed. PMID- 1920162 TI - Fast temporal adaptation of on-off units in the first optic chiasm of the blowfly. AB - 1. We recorded from spiking units in the first optic chiasm between lamina and medulla in the brain of the blowfly (Calliphora vicina). Both previously characterized neuron types, on-off units and sustaining units, were encountered. On-off units had a temporal frequency response with a lower cut-off frequency than blowfly photoreceptors. This low cut-off frequency is related to a fast temporal adaptation of the on-off units to trains of short light pulses. Temporal adaptation occurred independently for short on- and off-pulses. 2. On-off units only responded to stimuli of relatively large contrast. Contrasts of less than 10% gave little or no response. PMID- 1920163 TI - Discrimination of visual motion from flicker by identified neurons in the medulla of the fleshfly Sarcophaga bullata. AB - 1. Responses to moving contrast gratings and to flicker have been studied in cells in the medulla of the fleshfly Sarcophaga bullata using intracellular recordings and stainings. Medullary neurons responded periodically to flicker. Those which primarily discriminated motion had periodic responses or DC shifts in membrane potentials or increased noise. Intrinsic neurons included a T1a cell which was directionally selective (DS) and specific non-DS amacrine cells (6 types) arborizing either distal or proximal to the serpentine layer. Among the 12 types of output neurons recorded, 1 projected to the lobula plate, 6 to the lobula (Tm and T2 cells). 3 to both the lobula and lobula plate (Y cells), and 2 to the central brain. 2. Irrespective of their projection, medulla neurons which arborize in the stratum of the L2 terminals respond to flicker as does L2 and have the simplest, primarily periodic, responses to motion. The responses have significant power at the second harmonic of the stimulus temporal frequency suggesting that a non-linear operation, such as multiplication, may occur in the L2 stratum. Cells with arbors coinciding with either of the two levels of L1 terminals have much more complex responses to motion. All cells projecting to the lobula plate responded periodically to movement in some direction(s). PMID- 1920164 TI - The roles of central and peripheral eclosion hormone release in the control of ecdysis behavior in Manduca sexta. AB - 1. Ecdysis, a behavior by which insects shed the old cuticle at the culmination of each molt, is triggered by a unique peptide hormone, eclosion hormone (EH). In pupal Manduca sexta, EH is released into the hemolymph just prior to ecdysis, and circulating hormone is sufficient to elicit this behavior. 2. Removal of the proctodeal nerves in prepupal animals eliminated the appearance of blood-borne EH, but ecdysis behavior occurred on schedule. Therefore, circulating EH is not necessary for the triggering of ecdysis. 3. In contrast, a set of dermal glands failed to show their expected bout of secretion after proctodeal nerve removal. Injection of exogenous EH rescued this secretion. Thus, circulating EH appears necessary for action on peripheral but not central targets. 4. A major reduction in EH immunostaining is seen in the proctodeal nerves just preceding ecdysis; this coincides with a greater than 90% reduction in extractable EH from this structure and the appearance of circulating EH. A similar, concomitant reduction was seen in central EH cell processes, suggesting release of peptide within the CNS. 5. Antidromic stimulation of the proctodeal nerve stumps following proctodeal nerve removal triggered precocious ecdysis. This result further supports the conclusion that centrally released EH is sufficient to trigger the motor program. PMID- 1920165 TI - Processing of behaviorally relevant temporal parameters of acoustic stimuli by single neurons in the superior olivary nucleus of the leopard frog. AB - Response characteristics of 130 single neurons in the superior olivary nucleus of the northern leopard frog (Rana pipiens pipiens) were examined to determine their selectivity to various behaviorally relevant temporal parameters [rise-fall time, duration, and amplitude modulation (AM) rate] of acoustic signals. Response functions were constructed with respect to each of these variables. Neurons with different temporal firing patterns such as tonic, phasic or phasic-burst firing patterns, participated in time domain analysis in specific manners. Phasic neurons manifested preferences for signals with short rise-fall times, thus possessing low-pass response functions with respect to this stimulus parameter; conversely, tonic and phasic-burst units were non-selective and possessed all pass response functions. A distinction between temporal firing patterns was also observed for duration coding. Whereas phasic units showed no change in the mean spike count with a change in stimulus duration (i.e., all-pass duration response functions), tonic and phasic-burst units gave higher mean spike counts with an increase in stimulus duration (i.e., primary-like high-pass response functions). Phasic units manifested greater response selectivity for AM rate than did tonic or phasic-burst units, and many phasic units were tuned to a narrow range of modulation rates (i.e., band-pass). The results suggest that SON neurons play an important role in the processing of complex acoustic patterns; they perform extensive computations on AM rate as well as other temporal parameters of complex sounds. Moreover, the response selectivities for rise-fall time, duration, and AM rate could often be shown to contribute to the differential responses to complex synthetic and natural sounds. PMID- 1920166 TI - Parallel processing of afferent input by identified interneurones in the auditory pathway of the noctuid moth Noctua pronuba (L.). AB - 1. Interneurones 501 and 504 are identified sound-sensitive interneurones in the pterothoracic ganglion of the noctuid moth Noctua pronuba. Both neurones receive monosynaptic input from the A1 afferent and experiments with current injection suggest that the synapse is chemical. The EPSPs evoked in either IN 501 or 504 by the A1 afferent do not facilitate. 2. Temporal integration in INs 501 and 504 was compared by presenting the moth with tones at repetition rates found in the search, approach and terminal phases of the echolocating call of a hunting bat. INs 501 and 504 differ in their capacity to resolve stimulus repetition rates because the mean decay times of their compound EPSPs differ by a factor of three, although both interneurones receive monosynaptic input from the A1 afferent. 3. The features extracted from the authentic, prerecorded, call of an echolocating bat at the level of the pterothoracic ganglion were examined by recording sequentially from a range of interneurones in the same preparation. The capacity of INs 501 and 504 to encode the various phases of the call was examined in the light of their measured mean decay times and related to the avoidance behaviour of the insect. PMID- 1920167 TI - The time course and frequency content of hydrodynamic events caused by moving fish, frogs, and crustaceans. AB - In the present study the time course and spectral-amplitude distribution of hydrodynamic flow fields caused by moving fish, frogs, and crustaceans were investigated with the aid of laser-Doppler-anemometry. In the vicinity of a hovering fish sinusoidal water movements can be recorded whose velocity spectra peak below 10 Hz. Single strokes during startle responses or during steady swimming of fish, frogs, and crustaceans cause short-lasting, low-frequency (less than 10 Hz), transient water movements. Low-frequency transients also occur if a frog approaches and passes a velocity-sensitive hydrodynamic sensor. In contrast, transient water movements caused by a rapidly struggling or startled fish or water motions measured in the wake of a slowly swimming (less than or equal to 47 cm/s) trout can be broadbanded, i.e., these water movements can contain frequency components up to at least 100 Hz. High-frequency hydrodynamic events can also be measured behind obstacles submerged in running water. The possible biological advantage of the ability to detect high-frequency hydroynamic events is discussed with respect to the natural occurrence of high frequencies and its potential role in orientation and predator-prey interactions of aquatic animals. PMID- 1920168 TI - Syllable-internal structure and the sonority hierarchy: differential evidence from lexical decision, naming, and reading. AB - Treiman (1983) and others have argued that spoken syllables are best characterized not as linear strings of phonemes, but as hierarchically organized units consisting of an onset (initial consonant or consonant cluster) and a rime (the vowel and any following consonants) and that the rime is further divided into a peak or nucleus (the vowel) and a coda (the final consonants). It has also been argued that the sonority (or vowel-likeness) of the consonant closest to the peak, which is a function of its phonetic class, may have an effect on the strength of boundaries determined by the hierarchical division of the syllable (e.g., Treiman, 1984). We examined the evidence for syllable-internal structure and for sonority in two experiments that employed visually presented stimuli and lexical decision, naming, and reading tasks. Our results provide support for the breakdown of the rime into a peak and a coda and for an effect of the sonority of the postvocalic consonant on that break. This pattern occurred only in our lexical decision tasks, so the effect is assumed to be postlexical. We did not find an effect of the onset-rime boundary, perhaps because of an unanticipated effect of word frequency. Our results are discussed in terms of phonological coding in short-term memory. PMID- 1920169 TI - Anxiety and depression in tinnitus sufferers. AB - This paper focuses upon the relationship between tinnitus and personality. One hundred and twelve members of a tinnitus self-help group completed psychological and tinnitus questionnaires. In line with prior studies we found that tinnitus was associated with elevated anxiety trait and depression. Unlike previous work, use of a validated subjective tinnitus scale allowed us to directly test the strength of association. Although both anxiety trait and depressive tendency were significantly correlated with overall tinnitus severity, the coefficients were of low magnitude. Advancing age was related to a reduction in depressive tendency; and being male was associated with lower anxiety and depression scores. While hypothesizing a bi-directional causality between personality and the impact of tinnitus, we acknowledge that only longitudinal research can unequivocally test this. PMID- 1920170 TI - Effects of emotional imagery on physiological and facial responses in Type A and Type B individuals. AB - Type A behavior was examined in relation to physiologic and facial-expressive changes associated with anger, fear and distress. Affect was induced by an imagery procedure in which subjects recalled and described actual, emotion related episodes. Type A was assessed by a structured interview. Subjects were healthy men, 21 Type As and 21 Type Bs, whose mean age was 39 yr. Type Bs showed higher systolic blood pressure responses and greater expression of negative affect than Type As. Data analysis also revealed a tendency for enhanced physiologic and facial responses of Type Bs relative to Type As to be greater during fear and distress than during anger. These results appear to reflect a coping process whereby Type A individuals show attenuated facial-expressive and physiologic reactivity as a means of maintaining a sense of control over aversive conditions. PMID- 1920171 TI - Cardiac failure: symptoms and functional status. AB - The associations between exercise capacity, symptoms and specific aspects of quality of life were examined in subjects participating in a trial of the treatment of heart failure. Patients were assessed on entry and after three months treatment. The principle symptoms were fatigue, breathlessness and chest pain. These limited the extent and speed of physical activities, restricted social, leisure and family life and were associated with emotional distress. There were associations between baseline exercise capacity and measures of quality of life. Change in exercise capacity during three months treatment was correlated with changes in measures of symptoms, limitation of activity and quality of life. The findings confirm the value of change in exercise capacity as a measure of functional status and suggest that it should be supported by a limited number of specific measures of quality of life. PMID- 1920172 TI - Types of aggressiveness and catecholamine response in essential hypertensives and healthy controls. AB - Relationships between plasma catecholamine responses, and levels and types of aggression in hyper- and normotensives were investigated by analyses of data obtained in a large psychophysiological experiment on 97 hypertensives (EH) and 98 normotensives (CO) each. Subjects were divided according to levels (high vs low) and types (repressed vs manifest) of aggressiveness according to self rating questionnaire scores. Their plasma catecholamine responses to defined stressors indicating sympathetic arousability were compared by four factor analyses of covariance adjusting for age. Repressed aggression was significantly more frequent among male EH, whereas manifest aggression was significantly more frequent among the male COs. High as compared to low hostility was associated with significantly elevated values of plasma epinephrine in EH but not in CO. The immediate norepinephrine stress response was blunted but showed a delayed increase during the subsequent period of rest in high aggressives of both the EH and CO group, a pattern particularly pronounced in repressed aggressive hypertensives. Neither cardiovascular reactions nor speed of performance were observed to be substantially different in subjects of repressed and of manifest hostility. It was concluded that aggression in general is characterized by a delayed norepinephrine stress response and that an association with high epinephrine is typical for aggressiveness in hypertensives. Repressed hostility, however, does not produce a sympathomedullary pattern substantially different from that of manifest aggression thus casting doubt on the physiological significance of repression claimed by Alexander. PMID- 1920173 TI - Emotional stability; its relationship to confidence in maintaining balance. AB - Previous failures to find an association between postural test results and the complaints of dizziness/imbalance were further investigated in neuro-otology out patients, testing in a range of everyday situations requiring balance. Three matched groups of patients were compared: those complaining of dizziness/imbalance; those reporting but not complaining of dizziness/imbalance; and those who had never experienced these symptoms as noteworthy. No difference was found between the groups in measures of postural performance, self-reported confidence in balance, or in several trait measures of fear/anxiety. However, confidence in balance was significantly correlated with fear/anxiety measures across the sample. The correlations were strongest in complaining patients and weakest in patients reporting but not complaining of dizziness/imbalance. The results suggest that psychological characteristics are likely to influence the reporting of symptoms of dizziness/imbalance. The contribution of vestibular and other balance disorders is unclear given that the three groups performed equally well on postural tests. PMID- 1920174 TI - Illness behaviour and anxiety in dental patients. AB - The Authors evaluate the influence of illness behaviour (measured by IBQ) on patients' delay in seeking dental treatment for caries or periodontal pathology, and the relationship with anxiety (measured by STAI) and with social--demographic and clinical data. One hundred patients were studied. Delay in coming for a dental visit is influenced by family habit, level of education and fear experienced. The 'late' patients present significantly higher scores for denial on the IBQ. More serious pathology is in relation with greater denial. Anxiety is positively correlated with the IBQ scales dysphoria, hypochondria, disease conviction, irritability and inversely with denial. PMID- 1920175 TI - The effects of moderate exercise training on psychological well-being and mood state in women. AB - The relationship between moderate exercise training (five 45 min sessions/week, brisk walking at 62 beta +/- 2% VO2max for 15 weeks, psychological well-being and mood state was investigated in a group of 35 sedentary, mildly obese women. A 2 (exercise (EX) (N = 18), and nonexercise (NEX) (N = 17) groups) x 3 (baseline, 6 week, 15-week testing sessions) factorial design was used with data analyzed using repeated measures ANOVA. Four psychological tests were administered: Daily Hassles Scale (DHS), General Well-being Schedule (GWB), Spielberger State Anxiety Inventory (S-Anxiety), and Profile of Mood States (POMS). The EX and NEX groups had significantly different patterns of change over time for GWB total scores [F(2,66) = 5.72, p = 0.005] and the GWB subscales 'energy level' and 'freedom from health concern or worry'. Scores for the EX group were elevated at both 6 and 15 weeks. General well-being total scores and subscale 'energy level' scores were significantly correlated with improvement in submaximal cardiorespiratory fitness (r = -0.41, p = 0.014; r = -0.40, p = 0.017, respectively). Exercise training also had a significant effect on frequency but not intensity of DHS scores, and S-Anxiety, with a significant decrease seen in the EX group at 6 weeks but not 15 weeks. Profile of Mood States scores were not significantly related to exercise training. These data support the results of other studies that have reported improvement in general psychological well-being with exercise training. PMID- 1920176 TI - Psychosocial correlates of reactivity in black and white men. AB - This study sought to clarify the relationship between cardiovascular reactivity, hostility, depression and ethnicity. Blood pressure and heart rate responses to a standard arithmetic stressor were analyzed in 97 unmedicated hypertensive and normotensive men. Hypertensives and normotensives showed similar increases from baseline on systolic and diastolic blood pressure and on heart rate. Among whites (N = 44), systolic and diastolic reactivity were related to lower scores on the Verbal subscale items of the Buss-Durkee Hostility Inventory (p less than 0.05, for both). Among blacks (N = 53), no such relationship was found. Heart rate reactivity was related to greater depression scores among whites (p less than 0.01), but not among blacks. Among black subjects, heart rate increases were related to higher scores on the Indirect Anger subscale items of the Buss-Durkee (p less than 0.05). These results suggest that the expression of emotion and reactivity to a psychosocial stressor may be socioculturally mediated. PMID- 1920178 TI - A survey of 658 women who report symptoms of premenstrual syndrome. AB - A treatment trial was briefly mentioned in two British publications and women suffering from premenstrual syndrome were invited to write to us. After initial screening, postal questionnaires were sent to all eligible women. Six-hundred and ninety-nine questionnaires were returned and of these 658 were included in the analyses. Although the results of the study need to be considered cautiously because of the unrepresentative nature of the sample, the survey was helpful in ascertaining the views of women who report PMS symptoms and what they had found helpful. The majority of respondents were aged in their 30s and were married with children. Over 60% were chronic sufferers, having had symptoms for 5 years or more. High proportions of the women experienced both psychological and somatic symptoms but it was the psychological symptoms which were perceived as the most distressing. Over 60% of the sample were ascertained as suffering from some degree of psychological distress and the same proportion had one or more social problems. Overall 84% had visited their GP for this problem and many had also visited gynaecologists, family planning clinicians and psychiatrists. Agencies offering alternative medicine were also frequently contacted and often found more helpful. Most women had tried more than one type of medication but no one treatment was found to be particularly helpful. PMID- 1920177 TI - Behavioural psychotherapy in the treatment of irritable bowel syndrome. AB - The irritable bowel syndrome is a highly prevalent condition whose underlying aetiology is not understood. While many patients respond to a combination of gastrointestinal antispasmodics, bulking agents and dietary manipulation, controlled clinical trials have suggested that the benefit is only marginal and is due mainly to the large placebo effect found in this condition, which has been calculated to range between 54 and 81%. Associations between the syndrome and psychological and social stresses suggest, however, that treatment involving a systematic approach to the management of symptoms may hold out real therapeutic possibilities. In the current study, 42 IBS patients were randomly allocated to either medical treatment or to behavioural psychotherapy with a nurse therapist. They were assessed initially and at 4 and 9 months. There was a general improvement over the 9 months on a number of physical and psychological symptoms measured. However, no differences were found between treatment groups except for changes in two avoidance scores. A significant correlation was found, however, between improvement in the bowel symptoms of IBS (stomach pain and diarrhoea) and improvement in the psychological symptoms measured by the Clinical Interview Schedule, suggesting a close interrelationship between the two. PMID- 1920179 TI - A tool for measuring the asthma self-management competency of families. AB - A tool for measuring a family's asthma self-management behaviour has been developed for a study examining the relationships of asthma self-management behaviour, knowledge, and psychosocial factors with various indices of morbidity in children with asthma. The tool involves a structured interview which includes three typical situations of asthma self-management (scenarios). Each of the scenarios is divided into graded challenges. A scoring schedule was developed according to the critical incidents of self-management inherent in each situation. This schedule was then applied to the verbatim transcripts of the subjects' responses. These were presented to 380 asthmatic children aged 5-11 yr and their primary caregivers. Inter-rater reliability, inter-rater agreement and test-retest reliability coefficients indicate that the scores obtained are stable across raters and time. Correlations between scores on different scenarios suggest there is a common factor of self-management competency across all scenarios, but families are better at some aspects of self-management than others. The distribution of scores for each scenario is presented. The place of this tool as a means of assessing self-management behaviour is discussed. PMID- 1920180 TI - Psychosocial factors and depression in torticollis. AB - Sixty-seven patients suffering from spasmodic torticollis, a neurological disorder in which involuntary contractions of the head produce an abnormal head posture, completed a booklet of questionnaires aiming to assess psychosocial adjustment. Twenty-four per cent of the patients were moderately to severely depressed. Overall, as a sample the patients were not acceptant of or adjusted to their illness. Cognitive and emotion-focused strategies were slightly more widely used than instrumental ways of coping. Both adaptive and maladaptive coping strategies were more frequently used by female than male sufferers. The number of individuals who were potential sources of social support was not high (mean = 2.7, SD = 1.2). The patients were, however, generally satisfied with the available support. Self-depreciation, lack of control over head position/movement and the resulting disability in activities of daily living, lack of satisfaction with available social support, and the use of maladaptive coping strategies accounted for 75% of the variance of depression in torticollis. Self depreciation, which was the most salient predictor of depression in torticollis, accounting for 59% of its variance, was itself shown to arise from the patient's negative body concept relating to the postural abnormality of the head. As the severity of illness and resulting disability contributed to depression, successful symptomatic treatment of torticollis would be expected to ameliorate mood. However, as the currently available medical treatments are not effective for all treated cases, and as the self-depreciation resulting from a negative body concept formed the core of depression in torticollis, cognitive-behavioural therapy could improve the quality of life of the depressed torticollis patient. PMID- 1920181 TI - Habituation and tinnitus: an experimental study. AB - The study is an experimental test of Hallam's habituation theory of tinnitus; this theory implies that the huge variation in suffering among individuals with about the same amount of tinnitus is due to differences in habituation to the perceived sound. Fourteen patients, seven 'complainers' and seven 'noncomplainers', participated in an experiment where we studied changes in skin conductance and heart rate responses to a series of tinnitus-like sound stimuli. No group differences in habituation were observed. We suggest that facilitatory processes, like disinhibition, may be more important than deficient habituation for the inability, in some individuals, to adapt to their tinnitus. PMID- 1920182 TI - The Rationality/Emotional Defensiveness Scale--I. Internal structure and stability. AB - In a 10-year prospective study, Grossarth-Maticek and colleagues reported that the tendency to repress and/or deny emotions was strongly predictive of cancer mortality. The method used to assess repression/denial was modified recently by Spielberger to form the Rationality/Emotional Defensiveness (R/ED) Scale. The present study investigates the psychometric properties of the R/ED Scale in 1236 male (mean age = 71.8 yr) and 863 female (mean age = 68.5 yr) participants in a 27-year follow-up of the Western Collaborative Group Study. Analyses revealed high interitem consistency (Cronbach's alpha = 0.77 and 0.78 for men and women, respectively) and two independent and stable factors that we labeled 'Anti emotionality' (27% of total variance) and 'Rationality' (21% of total variance). Excluding cancer subjects, significant gender differences were observed for individual items, total R/ED score, and the two subscales. Comparisons of the 159 male cancer patients and the 175 female cancer patients with the corresponding noncancer subjects suggest possible gender x cancer status and age x cancer status interactions. These results challenge Grossarth-Maticek's assertion that rationality/anti-emotionality is a unidimensional construct and indicate the need to take into account the effect of age and gender on the presence of these psychological constructs. PMID- 1920183 TI - Premenstrual syndrome in hysterectomized women: mood and physical symptom cyclicity. AB - In 36 hysterectomized women presenting with PMS, a daily record of eight mood states and five physical symptoms was kept during 109 ovarian cycles. Premenstrual tension (PMT) was estimated at a point 92% through the ovarian cycle after fitting a five-term Fourier series to the data. Although significant mood and physical-symptom swings were common (present in 71% and 69% of cycles respectively), the incidence of symptoms late in the luteal phase (PMT) was low (36%). In nine women no PMT was detected, in twenty-two women PMT was sporadic, and in five there was evidence of the consistent appearance of both mood and physical symptom-related PMT. Symptoms clustered significantly around a point 85% through the ovarian cycle for moods, and 83% for physical symptoms; this differs significantly from the 92% observed in menstruant women with PMS and is consistent with the removal of a factor associated with menstrual onset, which may contribute to the symptoms perceived by women as PMT. PMID- 1920184 TI - Predictability of psychic outcome for exercise training and exercise training including relaxation therapy after myocardial infarction. AB - Predictability of the psychic outcome for two cardiac rehabilitation programmes was investigated in 119 myocardial infarction patients. They were randomly assigned to either a five-week daily exercise training or to an identical training in combination with six sessions of relaxation therapy, individually. The psychic outcome was constructed as a composite measure of change on six psychological questionnaires. The aim was to determine the predictive qualities of base-line: (1) clinical data; (2) exercise testing; (3) psychosocial information derived from interview; and (4) validated psychological questionnaires and whether the kind of rehabilitation programme has any influence on the predictive qualities of the variables. The psychic outcome turned out to be highly predictable (multiple correlation of 0.72). Predictors of relatively high importance were age, work-status and job-level, followed by mild heart failure, diastolic blood pressure and heart rate, all of them dependent upon the kind of treatment. It implies that the type of rehabilitation programme modified the effect of the determinants of psychic outcome. This research strategy is promising and deserves to be stimulated in order to build rehabilitation programmes tailored to the needs and abilities of the individual patient. PMID- 1920185 TI - Life stress and non-ulcer dyspepsia: a case-control study. AB - Sixty-two patients with persistent NUD symptoms were compared with healthy persons of comparable age, sex and social status on a variety of life stress, personality, mood state and coping measures. Highly threatening chronic difficulties were significantly more evident in the NUD group than controls (98 and 2% respectively), as were acute life events which remained highly threatening one week after their onset. Other psychological variables significantly related to NUD were high levels of anxiety and depressive symptoms, personality traits indicating neurotic or anxious tendencies, a tendency to use less mature stress coping mechanisms and to have less high-quality emotional support. Multivariate analysis revealed the presence of highly threatening stressors to be by far the most important predictor of NUD status. The implications of these findings in relation to the significance of stress and other psychological variables in the aetiology and treatment of NUD are discussed. PMID- 1920186 TI - Baroreflex sensitivity at rest and during stress in individuals with a history of vasovagal syncope. AB - The baroreflex sensitivity of healthy young adult males who reported some history of vasovagal syncope during emotionally stressful situations (e.g. blood donation) was compared to a control group of individuals who reported no such history. The baroreflex, which induces compensatory bradycardia and vasodilation in response to acute elevations of blood pressure, was examined as a possible mechanism underlying predisposition to vasovagal reactions. Changes in heart rate and vasoconstriction in response to baroreflex stimulation (negative external cervical pressure) at rest and during administration of a mental arithmetic task and a constrictive pain stimulus were assessed. Individuals with a history of vasovagal reactions displayed greater baroreflex sensitivity during the pain stimulus and at rest, but not during mental arithmetic. These findings suggest one mechanism of risk for syncope reactions, particularly in situations involving the experience of pain. PMID- 1920187 TI - Self-reported and genital arousal changes in sexually dysfunctional men following a sex therapy program. AB - This investigation examined the question of whether differences in psychophysiological and self-reported sexual response between sexually dysfunctional men and sexually functional men are reduced following treatment in a sex therapy program. Patterns of sexual responding before and after treatment in nine men with erectile difficulties and/or low sexual desire were compared with those of nine age-matched controls tested at the same intervals. Results indicated: (1) increased genital and self-reported response during the post-test in dysfunctional men but not in controls; (2) conditions eliciting performance demand produced less inhibition during the post-test in dysfunctional men; and (3) moderate correlations in dysfunctional men between clinically-assessed improvement in sexual functioning and actual changes in penile and self-reported arousal from the first to the second laboratory session. The implications of these data for the understanding of variables responsible for improved sexual functioning, and therefore, to clinical assessment and therapy, are discussed. Possible cognitive strategies are provided to account for discrepancies in self reported and physical sexual arousal in dysfunctional subjects, and the efficacy and limitations of using psychophysiological methods in studying sexual response in dysfunctional men are suggested. PMID- 1920188 TI - Multiple chemical sensitivities (MCS) PMID- 1920189 TI - Combating the social isolation of chronic mental illness. AB - 1. The diminished mental and emotional resources suffered by those with chronic mental illness (CMI) often lead to impoverished relationships that fail to produce satisfying connections with others. As a result, persons with CMI are frequently chronically lonely. 2. Moreno's sociometric principles and psychodramatic techniques for group therapy provide ways to increase interconnectedness with others by interrupting the self-reinforcing aspects of social isolation. 3. Role reversal, self-presentation, psychodramatic encounter, and sociometric exercises facilitate expanded emotional repertoire, let members know each other, provide relief from emotional distress, and produce information about the group needed to generate interaction. PMID- 1920190 TI - The expanded role of nurse case managers. AB - 1. Effective nursing practice is responsive to the changing needs of clients. The community, rather than the hospital, has become the primary treatment setting in which the long-term mentally ill manage their daily activities. 2. The professional role of rehabilitative nurse case management can provide an opportunity for nurses to expand their roles and develop new career directions. 3. The primary nursing model provides an excellent foundation for acquiring the attitudes and skills necessary in the delivery of a comprehensive rehabilitative model of case management. PMID- 1920191 TI - Pet project. The use of pet facilitated therapy among the chronically mentally ill. AB - 1. The effects of animal companions on people can be of therapeutic benefit. Using pet facilitated therapy with the chronically mentally ill as a treatment modality offers great potential for positive patient care outcomes. 2. Initiating a pet facilitated therapy program involves establishing policy and procedures regarding animals at the facility. The personality and animal experiences of the patient must be taken into consideration for pet selection. 3. Evaluate the effectiveness of the pet facilitated therapy program. Assess your patient care outcomes to design further interventions. PMID- 1920192 TI - Neuropsychological effects of AIDS studied. PMID- 1920193 TI - The original purpose. PMID- 1920194 TI - Education alone may be ineffective against AIDS. PMID- 1920195 TI - When disaster strikes. The concerns of staff nurses. AB - 1. This study determined how involvement with an earthquake affected patient care delivery and ascertained what nurses need to continue providing safe and efficient care in future disasters. 2. Although 60% of the staff had experienced a previous disaster, the literature described that learned coping does not automatically "transfer" to present loss experiences. 3. Providing staff with debriefing sessions and other support groups is helpful in the post-trauma period. At all levels, there is a need to communicate concerns and to be involved in disaster drills and other disaster preparedness sessions. PMID- 1920196 TI - On public sector psychosocial nursing: a conceptual framework. AB - 1. Nursing practice is driven more by its environment than by knowledge provided by faculty or even strong relationships between faculty and staff. Because that environment is publicly supported, programs reflect changes in the ideological environment. 2. The psychosocial nursing specialty incorporates psychiatric/mental health nursing and social sciences to reduce the negative environmental influences while increasing the positive ones. 3. Public sector psychosocial nurses must be familiar with changing laws and regulations as well as the history of hospital and community programs for the mentally ill; understand the complexity of society and that the state hospital is only one component of a large system; and contribute to the development of their subspecialty. PMID- 1920197 TI - Establishing therapeutic programs in the public sector psychiatric hospital: rethinking the possibilities and priorities. AB - In public sector hospitals, many patient therapeutic needs are easily identified, but multiple variables present in the system obscure the planning and implementation to meet these needs. Contextual variables that hinder program development include the physical environment; patient population; lack of guiding treatment philosophy; inconsistent approach; staff limitations; resistance to change; morale issues; and bureaucratic impasses. Assessment of the system culture is essential; determining the possibilities and priorities of the system will aid in designing and implementing projects or programs. PMID- 1920198 TI - Coordinating psychosocial nursing care across treatment settings. AB - A criticism sometimes made of nurse practitioners is that they want to be or think they are doctors. Who has not heard a nurse administrator accused of having lost her nursing identity, or of a faculty person who no longer knows nursing? Before BSN degrees were common, there were stories of 4-year nurses who believed they were above providing direct care and identified only with the administrative roles on the unit. These criticisms have been made by nurses. It is only recently that nurses are recognizing that fragmentation of the profession along these and other lines disempowers us and may result in non-nurses delineating what our practice will be. Perhaps stimulated by the nursing shortage and an increased awareness of our collective power, nurses are more vocal and we are owning our identity as nurses. Psychosocial nurses, perhaps because of conflicts related to professional territory with psychiatry, psychology, and social work, or because of the ramifications of third party payments, are less likely to assume the generic title of "therapist" than in the past. More often, there seems to be a coming together of psychosocial nurses with each other and with the nursing community as a whole. This coming together enhances the potential for nurse-to nurse communication and sets the stage to allow nursing to become the bridge needed by consumers of mental health services. I am hopeful that psychosocial nursing will meet this challenge. PMID- 1920199 TI - A proposal for change to achieve competence in long-term psychosocial nursing care. AB - Psychiatric nursing in a large institutional setting presents challenges to the nursing staff, who must remain competent in the specialized areas of psychiatric and medical nursing. Chronically mentally ill individuals present complex and continuing nursing care needs that must be addressed using a holistic approach to nursing assessment and care. The complex needs of nursing staff and patients in an institutional setting have been described. Methods of assisting the nurse to achieve competence using education and experience have been implemented and described with the goal of improving holistic nursing care to chronically institutionalized individuals. PMID- 1920201 TI - Public sector psychosocial nursing. PMID- 1920200 TI - Treatment dilemma: a political science perspective. AB - 1. The hallmark of a free society is that adults are free to choose their own life plans. Those who are mentally ill with impaired rationality often experience a severe reduction in their freedom to act out personal life plans. 2. A paternalistic care environment in a liberal state will foster a treatment modality that promotes development of the ability to think, choose, and act in a rational manner and allows the recovering individual to practice the liberty to choose. 3. A common language and group consciousness must be developed, as well as a willingness of those involved to sacrifice some of their individual needs and desires to work toward providing a paternalistic care environment for the mentally ill as a common good. PMID- 1920202 TI - Conceptualizing psychosocial nursing in the jail setting. AB - 1. The deinstitutionalization movement led to the release of thousands of mentally ill patients, many of whom were incarcerated as a way of dealing with their disturbed behavior. More restrictive civil commitment laws have also contributed to the number of mentally ill who are incarcerated. 2. Health care and security can be perceived as competing interests in the correctional institution. These competing interests may also be perceived as sources of conflict because each interest aims towards divergent goals that interfere with the other. 3. A problem central to the inadequate services for the mentally ill offender is that few people are aware of the poor conditions for this population. Correctional and mental health organizations must educate the public about the plight of the mentally ill offender. PMID- 1920204 TI - The place of research in the training of a physician. PMID- 1920203 TI - Psychosocial nursing in public versus private sectors: an introduction. PMID- 1920206 TI - Medical aspects of exercise. Benefits and risks. Summary of a Report of the Royal College of Physicians. PMID- 1920205 TI - Black looks ... at inducements. PMID- 1920207 TI - Cardiological intervention in elderly patients. Report of a Working Group of the Royal College of Physicians. PMID- 1920210 TI - Original manufacturers' packs and patient information leaflets--a patient's protection and right to know. PMID- 1920208 TI - A census of medical registrars in England and Wales, 1990. PMID- 1920209 TI - Self-poisoning patients discharged from accident and emergency: risk factors and outcome. AB - In a prospective audit of 1,096 consecutive attendances by deliberate self poisoning patients at an accident and emergency department (A&E), such patients were discharged directly from A&E on 31% of occasions. Outcome and risk were compared for patients admitted to hospital and discharged directly from A&E. In the following year repetition of self-poisoning occurred in the same proportions of patients admitted to hospital and discharged from A&E (12%, relative risk 1.02). Suicide during the following three years occurred in 1.3% of patients admitted and 1.1% of those discharged (relative risk 1.2). Patients admitted to hospital from A&E were those likely to be at greater risk: they were older, reported more physical ill-health, expressed a threat or left a note more often, and had more frequently experienced psychiatric inpatient care. Thus, nearly one third of deliberate self-poisoning attenders were discharged from A&E; outcomes were similar despite higher risk among admitted patients, suggesting that brief admission has some benefit. PMID- 1920211 TI - Free good--curse or cure? The Samuel Gee Lecture 1991. PMID- 1920212 TI - Patient access to medical records. PMID- 1920213 TI - The 1991 National Health Service reforms and their implications for patients, doctors and medical students. PMID- 1920214 TI - The International Red Cross and Red Crescent Movement. PMID- 1920215 TI - Medical services in the Royal National Lifeboat Institution. PMID- 1920216 TI - Appropriate voiding frequency in children with a history of urinary tract infections. PMID- 1920217 TI - Guidelines for the management of acute urinary tract infection in childhood. PMID- 1920218 TI - Exit examination. PMID- 1920219 TI - Intrauterine growth retardation does not cause cardiovascular disease. PMID- 1920220 TI - Lumbar puncture at The National Hospital, Queen Square. PMID- 1920221 TI - Atopic eczema. PMID- 1920223 TI - The crucifixion. PMID- 1920222 TI - Deceased or deceit? PMID- 1920224 TI - What's new in breast disease. PMID- 1920225 TI - Familial breast cancer. AB - The genetic inheritance of familial breast cancer is complex and heterogeneous, i.e. it cannot be explained by one major susceptibility gene. It is likely that the chromosomal abnormalities and genetic lesions detected in the inherited syndromes will be implicated in the development of the more common sporadic breast tumours. Study of this important subgroup is essential to advance our understanding of the tumour biology of breast cancer and to develop adequate screening programmes for high risk young women. PMID- 1920226 TI - Echocardiography in acute limb ischaemia. AB - In a retrospective study carried out over a 5-year period, 88 patients with acute limb ischaemia underwent echocardiography. Of this group, 74 were thought to have an embolic cause of ischaemia on either operative or arteriographic findings. Two dimensional echocardiography detected a cardiac source in 30 patients (sensitivity 41%, specificity 100%). Clinical examination on admission correctly indicated an embolic source in 36 patients (sensitivity 49%, specificity 36%). The combination of echocardiography and clinical examination detected an embolic source in 60 of 74 (81%) patients. In this study echocardiography complemented clinical examination in the diagnosis of a cardiac source of acute limb ischaemia. PMID- 1920227 TI - Blunt trauma-induced upper extremity vascular injuries. AB - Penetrating vascular injury which is associated with a satisfactory response to treatment occurs more commonly than blunt injury in the upper limb. Blunt trauma is a complex entity with associated soft tissue and skeletal injuries that may determine outcome irrespective of successful vascular repair. We reviewed 50 patients with upper limb vascular injury of which 43 were due to blunt trauma and seven to penetrating trauma. All patients with penetrating trauma had a good result without loss of limb function. Eight amputations and residual poor limb function in ten patients confirm the poor results of blunt injury. Associated nerve damage, responsible for nine of the ten poorly functioning limbs, is the most important determinant of outcome in limbs surviving the peri-traumatic period. PMID- 1920228 TI - Acute aortocaval fistula in association with ruptured aortic aneurysm. AB - Eight cases of aortocaval fistula are described. In all of them operation was performed with repair of the fistula and replacement of the aneurysm by a prosthetic graft. In seven cases the cause was rupture of an atherosclerotic aneurysm but one case followed rupture of a re-entrant dissecting aortic aneurysm. A fistula is most easily recognized by the sensation of a palpable thrill over the aorta during operation together with systemic venous congestion and a high central venous pressure before aortic clamps are applied. Diagnosis of the fistula before surgery or its recognition during operation and before opening the aorta usually leads to a successful outcome. PMID- 1920229 TI - Comparison of postpyloromyotomy feeding regimens in infantile hypertrophic pyloric stenosis. AB - One hundred infants undergoing pyloromyotomy were studied prospectively to ascertain the optimum time at which to reintroduce feeds after operation. The babies were randomized to be fed after 4 or 18 h and were then assessed by monitoring the frequency of postoperative vomiting and the number of days taken to achieve full oral feeding. There was significantly more postoperative vomiting in the early group, while both groups required the same number of days to achieve full oral feeding. The conclusion reached was that a delay in the reintroduction of feeds until 18 h after pyloromyotomy is to be recommended. PMID- 1920230 TI - Hydatid cysts in children: report of 88 cases. AB - Eighty-eight children (37 female, 51 male) with hydatid cyst disease were treated at the Pediatric Surgery Clinic of Ankara SSK Hospital, Turkey, in the period from 1977 to 1987. The ages of the children ranged from 3 to 14 years; 79 (89.8%) were older than 6 years and only nine (10.2%) were under 6 years. Liver and lung were the most frequent sites of involvement. Various surgical techniques were used in the treatment of the cysts. In this series obliteration of the cyst cavity by suturing (capitonnage) and omentopexy proved to be the best choice of surgical treatment in order to minimize the morbidity. PMID- 1920231 TI - Early and late surgical complications of subtotal oesophagectomy for squamous carcinoma of the oesophagus. AB - The use of stapling devices in oesophagogastric anastomosis has markedly reduced the incidence of anastomotic leakage, but may be associated with a higher incidence of stricture formation. The purpose of this study was to review the incidence, morbidity, management and outcome of leakage and stricture in patients undergoing subtotal oesophagectomy. Seventy-two consecutive patients with proven squamous carcinoma of the thoracic oesophagus who underwent subtotal oesophagectomy and gastric pull-up with stapled anastomosis were studied. Thirty six patients had the anastomosis constructed using the EEA size 25 mm circular stapler (group 1). Thirty-six patients had oesophagogastric reconstruction using the EEA size 28 mm circular stapler (group 2). Data were collected prospectively, but the groups were not randomized. One clinical/radiological anastomotic leak (3%) occurred using the 25 mm gun (group 1), but no dehiscence was demonstrated in group 2. There was no 30-day mortality, but two patients died before leaving hospital (overall hospital mortality rate, 3%). Early complications included anastomotic bleed, respiratory failure, chylothorax, transient bilateral recurrent laryngeal nerve palsy, and severe chest infections. After surgery, the patients were followed up at 1 month, at 3 months and then at 3-monthly intervals up to 1 year. Stricture formation occurred in 11 patients in group 1 and only four patients in group 2 (chi 2 test P less than 0.05). All benign strictures presented within 6 months of surgery. These strictures were satisfactorily treated by endoscopic dilatation. Two patients (one from each group) suffered anastomotic recurrence of their tumour at 8 and 10 months respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920232 TI - Carcinoma of the gallbladder: a diagnostic challenge. AB - Since the introduction and availability of abdominal ultrasound and computed tomography, 38 patients have been admitted to the Department of Surgery, Queen Mary Hospital, University of Hong Kong with a subsequently confirmed histological diagnosis of carcinoma of the gallbladder. The majority of patients presented with abdominal pain, anorexia or weight loss, jaundice, and anaemia or an abdominal swelling. Abnormal liver function tests were found in 70-90%. Cholangiography, ultrasound and particularly computed tomography helped to confirm clinical suspicion when performed but 23 patients (61%) had an inaccurate diagnosis made before surgery. Operative intervention was only of benefit when the carcinoma was confined to the gallbladder (median survival after cholecystectomy alone 13 months; other procedures 2 months; P less than 0.01). Carcinoma of the gallbladder carries a poor prognosis but ultrasound and computed tomography can help select patients for appropriate treatment (surgery, endoscopic stenting, radiotherapy, chemotherapy) if clinical suspicion is raised. PMID- 1920233 TI - Eye protection for the surgeon. AB - The surgeon today is obliged to operate on an increasing number of patients who are classed as high risk. A study is presented which examines the extent of potential corneal contamination with blood or tissue fluids, during common orthopaedic operations. In all, 65% of goggles worn by surgeons during the study were contaminated. The greatest risk was associated with operations around the hip joint, which are among the commonest orthopaedic procedures. Increased contamination was associated with the use of power tools and irrigation. The contamination rate of the protective flaps at the side of the goggles was relatively low (5%) suggesting that ordinary spectacles, which are more convenient and comfortable than the standard issue goggles, would provide adequate protection during routine use. PMID- 1920234 TI - Gangrene of the foot following peripheral phlebography. PMID- 1920235 TI - Salmonella infection of the aorta. PMID- 1920236 TI - Oesophagogastrostomy in the management of benign oesophageal strictures. PMID- 1920237 TI - Late appendicocutaneous fistulae. PMID- 1920238 TI - Spontaneous rupture: a new complication of splenosis. PMID- 1920239 TI - Combined lower cranial nerve injury: complication of upper cervical or basal skull fracture. PMID- 1920240 TI - Experience with full thickness scalp burns. PMID- 1920241 TI - Rib tip syndrome with unilateral renal agenesis. PMID- 1920242 TI - Detached thyroid nodule. PMID- 1920243 TI - Trigger thumb in children: results of surgical correction. AB - Stenosing tenosynovitis of the thumb, or trigger thumb, is relatively uncommon in children. The surgical correction of trigger thumb in 15 children is described to illustrate the clinical features of this condition. The literature is reviewed in order to alert the orthopaedic surgeon to the natural history of triggering digits in childhood. PMID- 1920244 TI - Accuracy and completeness of orthopaedic computer audit. AB - The completeness of data contained in a microcomputerized audit system has been compared with the operating theatre record book. The computerized audit system contained details of only 63% of the operations performed. Of the missing patients, 52% had never been completed. There were no failures of the computer system itself. Serious deficiencies in the methods of data entry were found and methods are described to overcome these deficits. The collection of audit information requires a disciplined approach and close supervision by a designated member of the surgical team. PMID- 1920245 TI - Separation of the Hastings hemiarthroplasty: report of eight cases. PMID- 1920246 TI - Non-traumatic method of joint release in clubfoot. PMID- 1920247 TI - Questionnaire identification of surgical patients at risk of HIV infection. PMID- 1920248 TI - Patients who were given information sheets have better postoperative recall of information. PMID- 1920249 TI - Management of urgent intact abdominal aortic aneurysms. PMID- 1920250 TI - Percutaneous gastrostomy: a simpler technique. PMID- 1920251 TI - Implantation of a central venous access device. PMID- 1920252 TI - Dyserythropoiesis, polymyopathy, and cardiac disease in three related English springer spaniels. AB - A polysystemic disorder was observed in three related English Springer Spaniel dogs that demonstrated regurgitation from an early age, slowly progressive temporal muscle atrophy with partial trismus, and less pronounced generalized skeletal muscle atrophy. All dogs exhibited moderate dyserythropoietic anemia, polymyopathy with megaesophagus, and varying degrees of cardiomegaly. The prevalence, etiology, underlying pathomechanism, and possible mode of inheritance remain to be elucidated. PMID- 1920254 TI - Endotoxemia in horses. A review of cellular and humoral mediators involved in its pathogenesis. AB - Endotoxemia remains the leading cause of death in horses, being intimately involved in the pathogenesis of gastrointestinal disorders that cause colic and neonatal foal septicemia. Endotoxins, normally present within the bowel, gain access to the blood across damaged intestinal mucosa, or endotoxemia occurs when gram negative organisms proliferate in tissues. Endotoxins are removed from the circulation by the mononuclear phagocyte system, and the response of mononuclear phagocytes to these lipopolysaccharides (LPS) play an important role in determining the severity of clinical disease. Macrophages become highly activated for enhanced secretory, phagocytic and cidal functions by LPS. Macrophage-derived cytokines are responsible for many of the pathophysiologic consequences of endotoxemia. The arachidonic acid metabolites, prostacyclin and thromboxane A2 likely mediate early hemodynamic dysfunction and the leukotrienes may potentiate tissue ischemia during endotoxemia. Interleukin 1 (IL-1) induces fever and is responsible for the inflammatory cascade, which constitutes the acute phase response. Tumor necrosis factor (TNF), an important proximal mediator of the effects of LPS, acts to initiate events and formation of other molecules that affect shock and tissue injury. Systemic administration of TNF produces most of the physiologic derangements that are associated with endotoxemia and antibodies that are directed against TNF significantly reduce LPS-induced mortality in experimental animals. In response to endotoxins, mononuclear phagocytes express thromboplastin-like procoagulant activity (PCA), which initiates microvascular thrombosis. Both IL-1 and TNF induce PCA expression, creating a positive feedback loop for LPS-induced coagulopathy. A macrophage-derived platelet activating factor contributes to coagulation dysfunction and further stimulates arachidonic acid metabolism. The ultimate consequences of endotoxemia are multiple system organ failure and death. The numerous feedback loops and intertwining cascades of mediators during endotoxemia defy simplistic methods of treatment. The optimal therapy likely involves methods to alter the generation of inflammatory mediators by mononuclear phagocytes. PMID- 1920253 TI - Efficacy and toxicity of VAC chemotherapy (vincristine, doxorubicin, and cyclophosphamide) in dogs with hemangiosarcoma. AB - Fifteen dogs with hemangiosarcoma were treated with a combination of vincristine, doxorubicin, and cyclophosphamide after incisional or excisional biopsy. The median survival for all fifteen dogs was 172 days (mean survival = 316 days). The median survival for those dogs with splenic hemangiosarcoma was 145 days (mean survival = 271 days) as compared with previously published median survival times in dogs with splenic hemangiosarcoma treated with surgery alone of 19 to 65 days. Toxicities included neutropenia (11/15), severe gastroenteritis (4/15), cardiotoxicity (3/15), and sepsis (2/15). The authors conclude that vincristine, doxorubicin, and cyclophosphamide chemotherapy may be an efficacious treatment modality in dogs with hemangiosarcoma and is associated with acceptable toxicity. PMID- 1920256 TI - Canine ehrlichiosis in six dogs with persistently increased antibody titers. AB - Chronic ehrlichiosis was diagnosed in six dogs on the basis of increased immunofluorescent antibody titers to Ehrlichia canis. Although clinical signs varied, all six dogs were anemic, hyperglobulinemic, and an IgG monoclonal gammopathy was documented in five dogs in which serum protein electrophoreses were performed. All dogs were treated with tetracycline for at least 14 days; four dogs also received immunosuppressive drugs. Clinical signs resolved within 1 week, hematologic abnormalities resolved in 1 to 5 months, and increased globulin concentrations normalized in 1 to 15 months; however, E. canis antibody titers remained increased for 15 to 31 months after initiation of treatment. Results of this study show that increased E. canis titers can persist in dogs with ehrlichiosis for many months after clinical recovery. PMID- 1920255 TI - Changes in factor VIII: coagulant activity and von Willebrand factor antigen concentration after subcutaneous injection of desmopressin in dogs with mild hemophilia A. AB - Four German Shepherd dogs with mild hemophilia A were given Desmopressin (Minirin intranasal solution, Ferring, Malmo, Sweden) subcutaneously at a range of doses in a controlled blind study. No substantial change in plasma FVIII activity was observed 0.5, 1, 2, 4, or 6 hours after administration of Desmopressin. Plasma von Willebrand factor antigen concentrations increased rapidly after doses of 0.4, 1.0, 2.0, and 5.0 micrograms/kg to mean values of 140%, 127%, 120%, and 140% of baseline, respectively. The duration of this increase was dependent on the dose of Desmopressin injected. PMID- 1920257 TI - Concurrent infection with Toxoplasma gondii and feline leukemia virus. Antibody response and oocyst production. AB - Four adult cats (two testing positive and two negative for feline leukemia virus FeLV) were fed Toxoplasma gondii tissue cysts collected from the brains of mice. Two control cats (1 FeLV+, 1 FeLV-) were not fed cysts. The cats infected with T. gondii shed thousands of oocysts but remained clinically and physically normal, with hemograms and clinical chemistry values essentially unchanged irrespective of their FeLV status. Infection with FeLV did not increase the duration of oocyst shedding. At necropsy no significant lesions were found. T. gondii antibodies were detected by three serologic tests in the cats fed tissue cysts. The time necessary for an antibody response to T. gondii was not altered by the FeLV infection. Indirect hemagglutination (IHA) was the least reliable of the serologic tests studied; it detected antibodies later in the infection, and titers were less than in the other tests. Latex agglutination (LA) detected antibodies a few days before IHA, but titers were less than in modified direct agglutination (MAT). MAT detected antibodies earliest in the infection and also measured antibodies in aqueous humor and cerebrospinal fluid. PMID- 1920258 TI - [Evaluation of radiation doses during radiological tests]. AB - The purpose of this document is to provide radiologists with a simple, but realistic means of determining the individual dose delivered to a patient during a radiological examination both in the region under investigation and at any other particularly sensitive organs. Fourteen types of examinations were considered corresponding to those most frequently carried out in France. The choice of examinations and methods of taking the films approaches as closely as possible, the average situations, and the frequency of different techniques is influenced by the results of a national study of radiodiagnostic examinations carried out in France in 1982. In the first section, the influence on the radiation dose of varying different physical parameters and techniques is analysed, with an aim of defining the limits of validity of the presented dosimetric values and the possible adaptation of these values to any individual situation, which is slightly different from these considered in this study. The second section describes the model used for determining the absorbed dose presented in the tables, concerning each type of examination, as well as bibliographic references referring to methods and results of determining the dose. The suggested calculation model may be used as a base for dose estimation for other types of examination. PMID- 1920259 TI - [A rare bone abnormality: intra-bone synovial cyst. Apropos of a case]. AB - One case of intraosseous ganglion is reported and compared with a review of the literature. The clinical findings, the physiopathological and radiological patterns are discussed as well as the differential diagnosis. PMID- 1920260 TI - [Diluted barium contrast agent for digestive opacification in abdominal x-ray computed tomography]. AB - Computed tomography is the gold standard technique for abdominal examination with a sliced-imaging modality, because actually US and MRI are not as available for studying hollow viscera. Oral opacification is necessary to analyze bowel loops, and complete iodinated venous injection which is indispensable to examine intra abdominal organs. Oral administration of a barium diluted contrast agent, is discussed in terms of tolerance, efficacy and administration mode. PMID- 1920261 TI - [X-ray computed tomographic study of the ethmoid and middle meatus. I. radioanatomy (coronal plane)]. AB - The advance of endoscopic endonasal surgery allows limited surgical resection in chronic rhinosinusitis. An accurate topographic evaluation of diseases and individual morphologic variation are necessary for this functional surgery. The preoperative radiological investigations require a precise knowledge of ethmoid and osteo-meatal unit anatomy. Thin sections by high resolution CT were performed in coronal plane. The anatomical land marks and the ethmoidal bony roots, which allow a study of the osteo-meatal unit and ethmoid air cells system, are showed. Like endoscopic view, coronal slices better display the different grooves for paranasal sinus draining and their relations with the ethmoid. PMID- 1920263 TI - [Use of ROC curves in medical imaging]. PMID- 1920262 TI - [Ante- and posthypophyseal insufficiency with infundibulum abnormalities]. AB - The hypopituitarism and the diabetes insipidus are often idiopathic. A retrospective study of 6 cases of diabetes insipidus and 8 cases of partial or total idiopathic antehypophyseal insufficiency has shown the value of MRI to demonstrate anomalies of the infundibulum or hypothalamic-hypophysis "stages". MRI allows to bring together some cases of idiopathic hypopituitarism in a new entity which is the hypopituitarism due to a newborn section of the infundibulum. PMID- 1920264 TI - Los Angeles water is not fluoridated. PMID- 1920266 TI - Time to adoption of an innovation by dentists in private practice: sealant utilization. AB - Dentists can be divided into five adoption categories based upon their time of adoption of pit and fissure sealants: innovators, early adopters, early majority, late majority, and laggards. The differences among dentists in the five adoption categories were examined for four classes of variables: practice characteristics, dentist characteristics, communication of information, and practice environment. Questionnaires were mailed in September 1984 to a random sample (N = 521) of Washington State dentists in general practices. A total of 376 completed questionnaires were returned, for a response rate of 72 percent. Adoption of sealants proceeded as follows: 5 percent of dentists through 1973, 24 percent through 1979, 50 percent through 1982, and 75 percent through 1984. Adoption category was related to percent of assistants who were certified, delegation to assistants and hygienists, magnitude of the fees charged by the practice, number of staff meetings per month, the dentist having been an officer in a dental organization, year the dentist adopted other new technologies, dentist's self rating of willingness to try new things, percent of patients who are children, and percent of the dentist's colleagues who used sealants. These data lend some support to the two-stage or opinion-leader model of diffusion and suggest that new technologies can be promoted by first influencing dentists who consistently adopt early. PMID- 1920265 TI - University of North Carolina caries risk assessment study. III. Multiple factors in caries prevalence. AB - The baseline caries experienced of approximately 5,000 children in South Carolina and Maine was used as the dependent variable in caries risk assessment analyses. Clinical, microbiologic, and demographic factors served as independent variables in a multivariate relationship to caries through regression and discriminant function analyses. Four factors--number of dental visits by the child in the past year, presence of white spot lesions, and both the urgency of need for restorative care and the future caries increment predicted by the examiner- associated significantly and consistently with caries prevalence in primary and permanent teeth of first and fifth graders at both study sites. Several factors associated significantly with caries prevalence at only one site or grade within a site, suggesting that wide applicability of a specific caries risk assessment model may be limited. In these analyses, sensitivity ranged from .60 to .72 and specificity varied from .86 to .91 in the four grade-site groups. The ultimate goal of this longitudinal study is to identify highly caries-prone children in time to prevent the occurrence of a future caries increment. Although the lack of consistent association of many variables, including microbiologic factors, with baseline caries prevalence was unexpected, it is expected that some of these variables will contribute predictive power in the prospective study. PMID- 1920267 TI - Legislation and reality in public dental services in Norway: dental health services for children and adolescents in 1975 and 1985. AB - The act relating to dental health service implied a reorganization of the public dental health services in Norway in 1984. The act intended to extend the target group of public dental health services and to achieve social and geographic equality in the distribution of dental health services among children and adolescents. The purpose of this study was to assess the degree to which these intentions had been fulfilled. The material comprised two nationwide, stratified, and randomly selected samples of 3,356 and 2,970 children and adolescents in the age group zero to 18 years. Data were collected in 1975 and 1985. Both the theoretical and the empirical models applied structural and individual resources to explain individual variation in use of dental health services. The results showed that the proportion of zero- to 18-year-olds who had seen a dentist within the past 12 months was higher in 1985 than in 1975 (81.7% and 75.8%, respectively). Bivariate and trivariate table analyses showed that statistically significant associations between structural resources and use of dental health services disappeared when controlling for a third variable. Use of dental health services among children and adolescents in Norway was not systemically influenced by the same factors, as was the use of dental health services in the adult population. Thus, the Public Dental Health Service in Norway seems to have had the capability of compensating for most of the discriminating effects that individual and structural factors may have on the use of dental health services both before and after the reorganization of the public dental health service. PMID- 1920268 TI - Changes in dental caries prevalence in upstate New York schoolchildren. AB - A survey of second and fifth grade children was conducted in upstate New York to determine recent trends in dental caries prevalence. Clinical examinations were conducted on 960 second grade and 837 fifth grade children in 51 schools. A single examiner derived the findings on a uniform basis using a standard protocol. An examination of changes in the percent of caries-free children and mean DMFS/dfs indices revealed that caries prevalence has continued to decline. Although the low SES group in this survey had consistently higher caries levels and a higher treatment need compared to the high SES group, the magnitude of the difference was much smaller compared to the previous survey. Because the sampling was restricted to young children in upstate New York, the trends observed should not be applied to a similar New York City population, to older children throughout New York State, or to children in other states. PMID- 1920269 TI - Educating dentists about fissure sealants: effects on knowledge, attitudes, and use. AB - This study evaluated the effects of three modes of education on dentists' knowledge, attitudes, and use of pit and fissure sealants. A randomly selected group of dentists was invited to participate in a sealant education initiative. During a 12-month period, a total of 662 dentists either (1) attended continuing education courses, (2) received written materials and videotapes by mail, or (3) received only written materials by mail. A comparison group (n = 337) received no materials until after the education phase and evaluation had been completed. Pre- and postintervention surveys were used to measure changes in knowledge, attitudes, and sealant use. Response rates to the two surveys were 62 percent and 76 percent, respectively. Preintervention values for knowledge scores, an attitude scale, and sealant use were similar among the four groups. At followup, the three education groups had significantly higher knowledge scores than the comparison group. Attitude values for all but one group were not significantly different, and sealant use by all groups was identical. The numbers of respondents not using sealants declined slightly between surveys in the three education groups while rising slightly in the No-Education Group. Because program outcomes were similar to those of another sealant initiative, it can probably be concluded that continuing education will increase dentists' knowledge about sealants, but have little effect upon their attitudes or their use of the technique. The changes observed in this investigation may be due to the particular capacity for cognitive and affective changes of participants, characteristics of the technology being promoted, and external forces in the professional environment. PMID- 1920271 TI - The John W. Knutson Distinguished Service Award in Dental Public Health--1990 recipient: Max H. Schoen. PMID- 1920270 TI - The Venturi Fluoride Saturator project. AB - This study was conducted to determine whether Venturi Fluoride Saturator (VFS) systems could be used to fluoridate small community and school water supply systems with an acceptable level of maintenance. VFS systems were installed and operated at four school and six community well sites according to state and federal regulations and recommendations. School VFS systems were unable to maintain optimum fluoride residuals even with substantial maintenance. All six community well site VFS systems performed acceptably, with only a few short lapses. VFS system maintenance was labor intensive. Recurring problems were caused by lengthy equipment delivery delays, the unavailability of timely technical assistance to support the VFS system, and the inadequate quality of VFS equipment and design. Based upon these findings, further expansion of the use of VFS systems either for community or school fluoridation cannot be recommended. Additional study of and improvements in the VFS system are indicated. Three major recommendations appear appropriate: (1) extensive laboratory testing of the VFS system concept under controlled conditions should be performed to determine the functioning parameters of this equipment under different hydrodynamic conditions; (2) additional research and development of the VFS unit to improve the quality of operations and the quality control of manufacturing and assembly should be undertaken; and (3) a VFS equipment distribution network should be developed, with sufficient logistical and technical support to supply equipment parts and expertise for installation, monitoring, and maintenance in a timely and efficient manner. PMID- 1920272 TI - American Board of Dental Public Health annual meeting. PMID- 1920273 TI - Oral Health policy challenges: Moving into the 21st century. PMID- 1920274 TI - Remarks upon receiving the 1990 Public Service Award of the American Association of Public Health Dentistry. PMID- 1920275 TI - Short-term effects of physiological and pharmacological doses of estradiol on estrogen receptor and uterine growth. AB - Estradiol (E2) regulation of estrogen receptor (ER) concentrations has been shown to be both time- and dose-dependent. E2 concentrations of 0.5 mg/ml or greater contained in Silastic capsules suppressed uterine ER concentrations after one day's exposure. In this study, we looked at the effects of physiological (1.0 and 10.0 micrograms subcutaneous injections) and pharmacological (5.0 mg/ml implants) doses of E2 on ER concentrations at times less than 24 hours. The implanted rats had maximum E2 plasma levels of approximately 2000 pg/ml for at least six hours which fell to around 800 pg/ml by 12 hours where they remained up to 24 hours. The physiological doses resulted in plasma levels at one hour of 2000 pg/ml (10 micrograms dose) and 250 pg/ml (1 microgram dose) both of which fell to less than 60 pg/ml by six hours. All treatments caused maximal ER suppression by six hours; however, the implants caused a greater reduction in ER levels than either of the physiological doses. The reduction of ER levels was due primarily to a decrease in the "cytosolic" receptor. Despite the decrease in ER, all doses caused a significant and equivalent increase in uterine weight at six hours, however, only the implanted animals maintained the maximal uterine weight gain through 24 hours. This maintenance of uterine weight appears to be correlated with a small but significant increase in the nuclear ER level over this same time period. Thus, while E2 can cause a short-term suppression of its receptor concentration with no effect on short-term uterine weight gain, uterine growth is positively correlated with the level of nuclear ER. PMID- 1920276 TI - Binding of epidermal growth factor (EGF) to a cultured human glioma cell line. AB - We have studied binding of 125I-EGF to the human malignant glioma cell line U-343 MG aCl2:6, which is planned to be used as a model system in studies of toxic effects of EGF conjugates. Special care has been taken to fulfil the requirements for a correct Scatchard analysis of binding parameters. Binding as a function of time, temperature and pH was investigated as well as dissociation and internalization of bound EGF. The stability of EGF during incubation was also determined. After binding to the receptor, EGF is rapidly internalized and degraded at physiological temperature. We found that binding experiments should be performed at 4 degrees C, since at this temperature practically no internalization took place, whereas dissociation occurred. From displacement experiments using increasing concentrations of unlabelled EGF competing with 125I EGF for binding, binding parameters were calculated using a computerized, nonlinear, least-squares regression analysis of binding data. We found that EGF bound to a class of high affinity receptors with an apparent dissociation constant KD of about 4 x 10(-10) M. The mean number of receptors was 25,000 per cell. In experiments where receptors were saturated with 125I-EGF an additional class of low affinity receptors was detected. This had an apparent KD of 1 x 10( 8) M with a mean receptor number per cell of 780,000. We also noticed enhanced dilution-induced dissociation of bound 125I-EGF in the presence of excess unlabelled EGF, suggesting negative cooperativity. PMID- 1920277 TI - Insulin receptor sub-types in a human lymphoid-derived cell line (IM-9): differential regulation by insulin, dexamethasone and monensin. AB - The cells of the human IM-9 lymphocyte-derived line contain a subpopulation of insulin binding sites which differ from classical insulin binding sites in their higher binding affinity for insulin-like growth factor II (IGF-II) and insulin like growth factor I (IGF-I). These atypical insulin binding sites are identified on IM-9 cells by [125I]IGF-II binding. To determine whether the atypical and classical insulin receptors of IM-9 cells were subject to different modes of in vivo regulation, we treated IM-9 cells with agents known to alter the surface expression of insulin receptors--insulin, dexamethasone and monensin. We then measured insulin and IGF-II binding to the surface of the washed cells. Pretreatment of IM-9 cells with 1 microM insulin for 20 h at 37 degrees C induced a 44-48% decrease in the number of high affinity insulin binding sites, but no change in the number of IGF-II binding sites. In contrast, the surface expression of both insulin and IGF-II binding sites (classical and atypical insulin receptors) increased 1.3 to 1.7-fold after treatment with dexamethasone (200 nM) and decreased 30 to 45% after monensin (1 microM). These results suggest that atypical and classical insulin receptors are differentially susceptible to down regulation by insulin. PMID- 1920278 TI - Maturational changes in opioidergic control of luteinizing hormone and follicle stimulating hormone in ram lambs. AB - Stimulation by naloxone, an opioid antagonist, of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion was examined in spring-born crossbred ram lambs raised under natural photoperiod. Vehicle (n = 6) or 1 mg naloxone/kg vehicle (n = 6) was injected (i.m.) 3 times at 2-h intervals at 5, 10 and 15 weeks of age and 4 times at 2-h intervals at 20, 25, 30 and 35 weeks of age. Blood samples were taken every 12 min for 6 h at 5, 10 and 15 weeks of age and for 8 h at 20, 25, 30 and 35 weeks of age. Naloxone had no effect on age at sexual maturity (controls 239 +/- 23 days; naloxone 232 +/- 33 days). The only significant (P less than 0.05) effect of naloxone on FSH was a greater pulse amplitude in 10-week-old treated lambs than in control lambs. Naloxone treatment resulted in greater LH pulse amplitude at 5 and 10 weeks of age (P less than 0.05), lower basal serum concentration of LH at 10 weeks of age (P less than 0.05), greater LH pulse frequency at 25 weeks of age (P less than 0.05), and greater mean serum concentrations of LH, basal LH and LH pulse amplitude at 35 weeks of age (P less than 0.01) than in the controls. In both groups of lambs, mean and basal FSH, and LH and FSH pulse amplitude were highest at 5 weeks of age and fell with age. LH pulse amplitude was lowest at 35 weeks of age (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920279 TI - Fertility in an F1 male hybrid of white-tailed deer (Odocoileus virginianus) x mule deer (O. hemionus). AB - The fecundity of an F1 male hybrid deer, from a cross between a male Odocoileus virginianus (white-tailed deer) and a female O. hemionus (mule deer), was assessed by cytogenetic and flow cytometric techniques. Analysis of chromosome morphology, nucleolus organizer expression, meiotic chromosome pairing, sperm production, and nuclear gene inheritance revealed no genetic anomalies that could potentially impair normal fertility. These observations are discussed in relation to recent reports of hybridization between natural populations of these two species. PMID- 1920280 TI - Artificial insemination of red deer (Cervus elaphus) with frozen-thawed wapiti semen. AB - Semen collected from wapiti (Cervus elaphus) in Canada in 1983 was frozen in two extenders. In 1988, the semen was used to inseminate 200 red deer hinds on 2 farms in New Zealand. Oestrus was synchronized in the hinds with progesterone impregnated intravaginal devices (CIDR); 200 iu pregnant mares' serum gonadotrophin was given to each hind on Day 11. The CIDRs were removed on Day 12 at 20/h, as the numbers of the hinds were recorded. On Day 14, 54-56 h after CIDR removal, the hinds were brought into the yards in the same batches and laparoscopically inseminated. Semen from three sires was used. The overall conception rate was 51%. Gestation length ranged from 239 to 247 days. One hind was lost at calving, 3 calves had to be hand raised and there were 2 neonatal calf deaths. PMID- 1920281 TI - Glucose and glutamine metabolism in pre-attachment cattle embryos in relation to sex and stage of development. AB - Individual Day-7 embryos (morulae to expanded blastocysts) were incubated with radiolabelled substrates and karyotyped to determine the sex. In Exp. 1, embryos were incubated for 3 h with D-[1-14C]glucose, as a measure of the activity of the pentose-phosphate pathway (PPP) and D-[5-3H]glucose, as a measure of total glucose metabolism. The labelled products 14CO2 and 3H2O were collected throughout the measurement period. Total glucose metabolism in male embryos was twice that in female embryos and increased between the morula and expanded blastocyst stages. Relative to total glucose metabolism, PPP activity was four times greater in female than in male embryos. In Exp. 2, embryos were cultured with D-[1-14C]glucose, and L-[3,4-3H(N)]glutamine (a measure of Krebs cycle activity) in the presence of brilliant cresyl blue, a stimulator of the PPP. Glutamine metabolism increased from the morula to expanded-blastocyst stages. Relative to the metabolism of glutamine, the activity of the PPP was one-third greater in female than in male embryos. PMID- 1920283 TI - Oestrogen production by the preimplantation donkey conceptus compared with that of the horse and the effect of between-species embryo transfer. AB - Aromatase distribution in membranes of preimplantation horse and donkey conceptuses was compared by measuring the incorporation of [3H]androstenedione into oestrone and oestradiol-17 beta. In the donkey conceptus, aromatase activity was similar in all the tissues examined (yolk sac, chorionic girdle and allantochorion), whereas in the horse it was generally lower and showed the relationship chorionic girdle greater than yolk sac greater than allantochorion. A higher proportion of labelled precursor was incorporated into oestradiol-17 beta by extra-embryonic tissues of the donkey compared with those of the horse. In contrast to previous results, aromatase in the chorionic girdle did not decline progressively before its migration into the endometrium on Day 36 to form the endometrial cups. The chorionic girdle of a donkey conceptus carried in the uterus of a mare failed to invade the surrogate horse endometrium and aromatase activity was still high in this tissue at Day 42. Aromatase distribution in 2 transferred donkey-in-horse conceptuses resembled that of the fetal, rather than the maternal, genotype indicating a lack of effect of the maternal environment. PMID- 1920282 TI - Gonadotrophin concentrations and ovulation rates in Suffolk ewes actively or passively immunized against inhibin alpha. AB - Mature Suffolk ewes were either actively or passively immunized against the synthetic fragment of porcine inhibin alpha, pI alpha(1-30), to determine the effects on gonadotrophin secretion and ovulation rate. Thirteen control ewes were immunized against human serum albumin, 12 ewes were actively immunized against pI alpha(1-30) and 36 ewes were passively immunized with pI alpha(1-30) antiserum. Blood samples were collected at 4-h intervals for 72 h from oestrus-synchronized ewes following the withdrawal of the progestagen pessaries. Mean gonadotrophin concentrations measured during the oestrous cycle of control ewes, ewes actively immunized against pI alpha(1-30) and ewes passively immunized against pI alpha(1 30) were similar, but their secretory profiles differed. Serum concentrations of follicle-stimulating hormone (FSH) were highest in ewes which had received antiserum at the time of pessary withdrawal; FSH concentrations did not decrease during the follicular phase of the oestrous cycle in ewes given antiserum 24 h after pessary withdrawal. Subtle but significant increments in serum FSH concentrations were observed in all passively immunized ewes in which sampling commenced at the time of treatment. The amplitude of the preovulatory luteinizing hormone (LH) peak, but not of the FSH peak, and the postovulatory secondary rise in FSH were lower (P less than 0.05) in actively immunized ewes than in control ewes. The mean (+/- s.e.) ovulation rate for actively immunized ewes (6.6 +/- 1.0) was 3 times higher (P less than 0.05) than that for control ewes (2.0 +/- 0.2), but was unaffected by passive immunization (range, 1.8-2.3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920284 TI - Molecular cloning and expression of human trophoblast antigen FDO161G and its identification as 3 beta-hydroxy-5-ene steroid dehydrogenase. AB - The monoclonal antibody FDO161G reacts with a 43-kDa protein found in human extravillous trophoblast, syncytiotrophoblast, adrenal cortex, interstitial cells of the testis and ovarian follicle cumulus cells. cDNAs for this protein have been isolated from the lambda gt11 library, sequenced, and expressed in COS-7 cells. The protein was identified as 3 beta-hydroxy-5-ene steroid dehydrogenase (HSD). The sequence of the HSD protein raises questions about its association with cell membrane systems. The lack of reactivity of FDO161G with other tissues suggests that HSD has a limited tissue distribution and that other enzymes may exist in peripheral tissues, which can convert delta 5 3-hydroxysteroids to delta 4 3-ketosteroids. PMID- 1920285 TI - Effect of ovulation on sperm transport in the hamster oviduct. AB - When hamsters mate shortly after the onset of oestrus (4.5-6 h before the onset of ovulation), spermatozoa are stored in the caudal isthmus of the oviduct until near the time of ovulation. At this time, a few spermatozoa ascend to the ampulla to fertilize the eggs. Superovulation resulted in a significant increase in the number of spermatozoa in the caudal isthmus at 6 h post coitus (p.c.) and in the ampulla and bursal cavity at 12 h p.c. Precocious ovulation resulted in a highly significant reduction in the total number of spermatozoa in the oviduct at 3 and 6 h p.c. This effect was completely overcome by intrauterine artificial insemination, suggesting lack of cervical patency as the block to sperm transport in precociously ovulated animals. Ligation of the ampulla-infundibulum junction in naturally ovulating hamsters resulted in significantly fewer spermatozoa in the caudal isthmus and ampulla at 12 h p.c. Preclusion of ovulation also resulted in fewer spermatozoa in the caudal isthmus and ampulla at 12 h p.c., suggesting that the products of ovulation stimulate sperm transport in the oviduct. PMID- 1920286 TI - Development of enucleated mouse oocytes reconstituted with embryonic nuclei. AB - The chromosomes of mouse oocytes at telophase of the first meiotic division were removed using micromanipulation and differential interference microscopy. The enucleated oocytes were used as recipients for nuclear transplantation, after culture for 4-6 h. The newly synthesized proteins of the enucleated oocytes showed the same pattern as those of secondary oocytes matured in vivo. When the enucleated oocytes received a nucleus from late 2- and 8-cell embryos, or a cell from the inner cell mass (ICM) of blastocysts, 23, 4 and 10%, respectively, of reconstituted embryos developed to blastocysts. After transfer to recipient females, live young were produced from the reconstituted eggs that received a nucleus from late 2-cell embryos. PMID- 1920287 TI - Walter Heape, FRS: a pioneer in reproductive biology. Centenary of his embryo transfer experiments. PMID- 1920288 TI - Mating behaviour and insemination in the hopping mouse (Notomys alexis). AB - Hopping mice have extremely small testes and a reduced complement of male accessory sex glands. Nevertheless, greater than 1000 spermatozoa populate the isthmus of the oviduct after each insemination and a range of morphological types is found similar to that in the male tract. When females are primed with gonadotrophins they sometimes lock with more than one of the males within the group and in the present study two inseminations sometimes took place at the one oestrus. There is thus the possibility for intermale sperm competition within the female tract of these animals. PMID- 1920290 TI - Plasma androgens in spotted hyaenas (Crocuta crocuta): influence of social and reproductive development. AB - Differences in plasma testosterone and androstenedione concentrations in male spotted hyaenas belonging to various reproductive and social categories 4 clans resident in South Africa and Botswana suggest that central-immigrant males have the highest concentrations of androgens, reflecting their roles as mating males. Social inhibition of reproductive function may occur in other males. A reversal in the ratio of testosterone: androstenedione occurs at puberty in most individuals, testosterone becoming the dominant hormone, especially in males that have procured mating rites. Cubs of either sex had low testosterone concentrations, except for a 4-day-old male that displayed adult concentrations, which were accompanied by a temporary testicular descent. Plasma testosterone concentrations in females largely reflected ovarian activity and showed no correlation with androstenedione concentrations. Female cubs had androstenedione concentrations significantly higher than those in all other social categories except for the central-immigrant males. The androgen profiles presented here suggest that the key to the behavioural dominance of female spotted hyaenas over males may lie with the neonatal developmental stages, rather than with the androgen patterns of adult animals. PMID- 1920289 TI - Relationship of oestrus synchronization method, circulating hormones, luteinizing hormone and prostaglandin F-2 alpha receptors and luteal progesterone concentration to premature luteal regression in superovulated sheep. AB - Ewes were treated with exogenous follicle-stimulating hormone (FSH) and oestrus was synchronized using either a dual prostaglandin F-2 alpha (PGF-2 alpha) injection regimen or pessaries impregnated with medroxy progesterone acetate (MAP). Natural cycling ewes served as controls. After oestrus or AI (Day 0), corpora lutea (CL) were enucleated surgically from the left and right ovaries on Days 3 and 6, respectively. The incidence of premature luteolysis was related (P less than 0.05) to PGF-2 alpha treatment and occurred in 7 of 8 ewes compared with 0 of 4 controls and 1 of 8 MAP-exposed females. Sheep with regressing CL had lower circulating and intraluteal progesterone concentrations and fewer total and small dissociated luteal cells on Day 3 than gonadotrophin-treated counterparts with normal CL. Progesterone concentration in the serum and luteal tissue was higher (P less than 0.05) in gonadotrophin-treated ewes with normal CL than in the controls; but luteinizing hormone (LH) receptors/cell were not different on Days 3 and 6. There were no apparent differences in the temporal patterns of circulating oestradiol-17 beta, FSH and LH. High progesterone in gonadotrophin treated ewes with normal CL coincided with an increase in total luteal mass and numbers of cells, which were primarily reflected in more small luteal cells than in control ewes. Gonadotrophin-treated ewes with regressing CL on Day 3 tended (P less than 0.10) to have fewer small luteal cells and fewer (P less than 0.05) low affinity PGF-2 alpha binding sites than sheep with normal CL. By Day 6, luteal integrity and cell viability was absent in ewes with prematurely regressed CL. These data demonstrate that (i) the incidence of premature luteal regression is highly correlated with the use of PGF-2 alpha; (ii) this abnormal luteal tissue is functionally competent for 2-3 days after ovulation, but deteriorates rapidly thereafter and (iii) luteal-dysfunctioning ewes experience a reduction in numbers of small luteal cells without a significant change in luteal mass by Day 3 and, overall, have fewer low-affinity PGF-2 alpha binding sites. PMID- 1920291 TI - Direct effects of oestradiol-17 beta and prostaglandin E-2 in protecting pig corpora lutea from a luteolytic dose of prostaglandin F-2 alpha. AB - Implants containing vehicle or oestradiol-17 beta (10 mg) were placed into pairs of corpora lutea (CL) with and without prostaglandin F-2 alpha (PGF-2 alpha) (100 micrograms) on Day 11 and CL were collected on Day 19, in cyclic gilts (Exp. 1). The results demonstrated that CL implanted with PGF-2 alpha with or without oestradiol-17 beta had a markedly lower (P less than 0.01) weight (mg) and progesterone concentration (ng/mg) than CL with vehicle-or oestradiol-17 beta implanted or unimplanted CL, which were similar (149 and 7.2 vs. 304 and 49.6, respectively). In Exp. 2, CL implanted with vehicle, oestradiol-17 beta or PGE-2 remained fully functional until Day 19, whereas CL implanted with oestradiol-17 beta +/- PGF-2 alpha and PGE-2 + PGF-2 alpha exhibited lower (P less than 0.05) weight and progesterone concentrations; CL implanted with PGE-2 + PGF-2 alpha were heavier (P less than 0.05) and tended (P less than 0.10) to have greater progesterone concentrations than CL implanted with oestradiol-17 beta + PGF-2 alpha. In Exp. 3, a dose-dependent (P less than 0.05) effect of PGE-2 on preventing regression induced by PGF-2 alpha was observed on Day 19. These data demonstrate a direct effect of PGE-2, but not of oestradiol-17 beta in protecting the CL against luteolysis induced by PGF-2 alpha. PMID- 1920292 TI - Effect of castration on plasma concentrations of luteinizing hormone and follicle stimulating hormone in adult Merino rams which were homozygous carriers or non carriers of the Booroola fecundity gene. AB - Before castration, the mean plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) did not differ between FF and ++ Booroola rams. After castration, mean LH and FSH concentrations increased after 8 h, and for the next 14 days the rate of increase in FSH, but not LH, secretion was significantly faster in FF than in ++ rams (P less than 0.05). Mean FSH concentrations over this period were significantly higher in FF than in ++ rams (P less than 0.05). In both genotypes, the ranked FSH values did not significantly change their order over time, i.e. a significant within-ram effect was noted (P less than 0.05). Repeated-measures analysis of variance indicated a significant effect of genotype on mean FSH secretion (P less than 0.05) and a significant effect of sire in the FF (P less than 0.05), but not the ++ (P = 0.76), genotype. From Day 28 to Day 58 after castration, FSH and LH concentrations were variable and no overall increases in concentrations were observed. The mean concentrations of both hormones over this period were not related to genotype. There were no gene-specific differences in pulsatile LH secretion 14 weeks after castration. However, the mean LH, but not FSH, response to a bolus injection of 25 micrograms of gonadotrophin-releasing hormone (GnRH) was significantly higher in FF than in ++ rams (P less than 0.05) and this was not significantly affected by sire. These studies support the hypothesis that the F gene is expressed in adult rams, in terms of pituitary responsiveness to an injection of GnRH and to the removal of the testes, but it is not clear from this study whether the influence of sire is related to or independent of the apparent gene-specific differences. PMID- 1920293 TI - Ovulation, fertilization and early embryonic development in the bitch (Canis familiaris). AB - Using circulating plasma hormone estimations, ovulation was monitored in bitches. The results obtained indicate that the timing of ovulation bears little relationship to alterations in sexual behaviour. The bitches were killed and reproductive tracts were removed at various intervals after ovulation and ova or embryos were recovered. The embryo stages were assessed visually and some were investigated histologically. Embryonic development, to early blastocyst stage, took place within the oviducts during the first 12 days after ovulation and there was a marked increase in size between the early and late blastocyst. A culture system using cells from the uterine tube supported the development of one 1-cell embryo to the morula stage. PMID- 1920295 TI - Energy metabolism in late preimplantation rat embryos. AB - The consumption of pyruvate and glucose, and the production of lactate, by single preimplantation embryos, was measured using a noninvasive technique. Embryos were cultured in 300-500-nl microdrops, for 8-12 h at a time, from Day 4 to Day 6 after mating, when they developed from the 8-cell stage to expanded blastocyst. Pyruvate was the predominant substrate at the 8-cell/morula stage; glucose uptake exceeded that of pyruvate after the onset of blastocoel formation. Lactate production increased in parallel with glucose consumption. For most stages, approximately 100% of the glucose uptake was accountable for by lactate production and in some cases an additional source of lactate must be postulated. Culture in vitro had little effect on lactate production, although a lower level of metabolism was observed compared with fresh blastocysts. Rat embryos were capable of developing to blastocysts in the absence of glucose, when lactate production was greatly reduced. PMID- 1920294 TI - Proliferative activity of gonocytes, Sertoli cells and interstitial cells during testicular development in mice. AB - Developing mouse testis was studied from Day 14 post coitum (p.c.) until Day 35 post partum (p.p.) by [3H]thymidine autoradiography. The gonocytes proliferated actively at Day 14 p.c., the [3H]thymidine labelling index (L.I.) being 7.5%, and were quiescent from Day 16 p.c. up to the first day of life, when spermatogenesis started. The L.I. increased to 20% at Day 2 p.p. The L.I. for the Sertoli cells was approximately 20% before birth. After birth the proliferative activity decreased. After Day 11 p.p., the Sertoli cells showed their typical adult appearance. After Day 17 p.p. no labelled Sertoli cells were observed. The Leydig cells featured a very low proliferative activity up to Day 21 p.p. (L.I. of maximal 1.9%). At Day 29 p.p. there was a peak of 7.4% in L.I., followed by a sharp decrease to 0.35% at Day 35 p.p. The L.I. of mesenchymal cells decreased from 11.4% at Day 14 p.c. to 1.1% at Day 14 p.p. and remained more or less constant thereafter. The proliferative activity of myoid, endothelial and perivascular cells followed a similar course to that of mesenchymal cells, their L.I.s being high before birth (16, 12.5 and 19%, respectively, decreasing until Day 14 p.p. (0.6, 2.0 and 1.2%, respectively) and thereafter being more or less constant. There was an increase in the relative number of Leydig cells from approximately 4% of the total interstitial cell number at Day 14 p.p. to 29.5% at Day 35 p.p. At the same time, the relative number of mesenchymal cells decreased from 55 to 13%. The diameter of the seminiferous tubules showed a peak of 92 microns at Day 16 p.c., decreased to 44 microns at Day 1 p.p. and increased again to 204 microns at Day 33 p.p. These results show that, except for the Leydig cells, the proliferative activity of testicular cell types is highest during the pre- and early postnatal period. The major outgrowth of the Leydig cell population occurs around the fourth week after birth. The results are in accordance with the hypothesis that the mesenchymal cells are the progenitors of Leydig cells. PMID- 1920296 TI - Plasma progesterone and luteinizing hormone concentrations and the role of the corpus luteum and LH gonadotrophs in the control of delayed implantation in Schreibers' long-fingered bat (Miniopterus schreibersii). AB - In Schreibers' long-fingered bat from South Africa (approximately 33 degrees S) copulation, ovulation and fertilization occurred in April and May, implantation was delayed until August, and parturition occurred in December. Delayed implantation coincided with winter, during which the bats remained active, only entering prolonged periods of torpor during particularly cold spells. Plasma progesterone concentration was low during non-pregnancy (1.54 ng/ml) and during delayed implantation (1.67 ng/ml), and thereafter increased to reach a peak mean of 64.82 ng/ml in late pregnancy. Changes in size and ultrastructure of the luteal cells indicated periods of steroidogenesis just after formation of the corpus luteum, and for about 2 months after implantation; reduced steroidogenic activity during delayed implantation; and luteolysis in the last 2 months of pregnancy. Plasma luteinizing hormone (LH) concentration and pituitary LH-beta immunoreactivity were highest during follicular development and peaked just before ovulation. During early delayed implantation, plasma LH concentration was low, and both plasma LH and pituitary LH-beta immunoreactivity increased from July, reaching peaks in late pregnancy. LH may be required to activate the corpus luteum and terminate delayed implantation, or, as in some small carnivores, it may be required for luteal maintenance. PMID- 1920297 TI - Evidence to support a follicle-stimulating hormone threshold theory for follicle selection in ewes chronically treated with gonadotrophin-releasing hormone agonist. AB - The mean and peak concentrations of follicle-stimulating hormone (FSH) during the luteal phase of a normal cycle were measured in 8 Welsh Mountain ewes. Gonadotrophin secretion and follicle growth were then suppressed by the chronic administration of the GnRH agonist buserelin for 5 weeks. During the 6th week of agonist treatment, each ewe was given a continuous infusion of FSH to produce a peripheral concentration of FSH equal to either the mean or peak of the gonadotrophin measured for that individual in the cycle preceding agonist treatment. Treatment had no effect on the total number of follicles, the number of follicles less than or equal to 2.5 mm in diameter or the in-vitro production of oestradiol by the small follicles when compared with control animals. None of the animals infused with the mean luteal-phase FSH equivalent developed large follicles greater than 2.5 mm diameter which could be classified as preovulatory follicles (oestradiol greater than 1000 pg/follicle/h). All of the animals infused with the peak luteal-phase FSH equivalent developed large follicles, some of which were preovulatory. The results suggest that an individual threshold concentration exists for FSH above which the later stages of preovulatory follicular development are stimulated. PMID- 1920299 TI - Does follicular dominance occur in ewes? AB - The process by which a single follicle is selected to ovulate while others regress is unknown in ewes. If the dominant follicle secretes substances that directly inhibit the growth of other follicles, the superovulatory response to the administration of exogenous gonadotrophins may be blunted. Administration of 1250 iu pregnant mares' serum gonadotrophin (PMSG) before or after the emergence of the dominant follicle in the follicular phase, or 1000 iu PMSG in the presence or absence of a large healthy or atretic follicle during the luteal phase did not affect the induced ovulatory response. Comparisons between the ovary with or without the dominant follicle did not reveal any differences in ovulatory response to PMSG. The in-vitro features (i.e. mitotic index, oestradiol and testosterone production) of follicles ipsilateral or contralateral to the dominant follicle during the early and late follicular phases were also similar. If the dominant follicle secretes substances detrimental to the other follicles, this could be mimicked in vitro. Co-culture of small follicles with the largest follicles in a closed system did not reduce their incorporation of 3H thymidine in granulosa cells, compared with small follicles cultured alone. These data suggest that dominance is probably not operative in sheep. The administration of 500 iu of PMSG during the midfollicular phase increased ovulation rate in Merino ewes, indicating that dominance is essentially passive in ewes and can easily be overcome by raising gonadotrophin concentration. PMID- 1920298 TI - Effect of insulin-like growth factor-I on protein synthesis in porcine embryonic discs cultured in vitro. AB - Porcine embryos at Day 13 (Day 0 = first day of oestrus) were collected surgically and embryonic discs were isolated microsurgically. The discs were washed and cultured in Dulbecco's modified Eagle's medium without serum, with either 14C-leucine alone or 14C-leucine plus insulin-like growth factor-I (IGF-I) (100 ng/ml) at 37 degrees C for 48 h in 5% CO2 in air. After incubation, discs were morphologically evaluated, frozen in liquid nitrogen and stored at -70 degrees C. No statistical differences in morphology were observed between embryonic discs cultured in medium with IGF-I and those cultured in medium alone (control). Although more radioactivity was incorporated by embryonic discs in the presence of IGF-I than by those cultured in medium without the growth factor, the difference between the two groups was not significant. From two-dimensional gel electrophoresis, it was observed that IGF-I selectively stimulated the synthesis of four new proteins with Mr of 24,000, 70,000, 77,000 and 95,000, respectively and pI between 5.5 and 6.5. At least 90% of the other proteins in the gels was synthesized in greater amount by embryonic discs cultured in the presence of IGF I than in the controls. These results show that IGF-I can stimulate protein synthesis in pig embryonic discs cultured in vitro and suggest that this growth factor may play an important role in regulating early development. PMID- 1920300 TI - Effect of gonadotrophin environment on growth and development of isolated mouse primary ovarian follicles. AB - Collagen gels containing isolated primary follicles devoid of other ovarian tissue were transferred beneath the kidney capsule of 3 types of female recipients: cycling, ovariectomized and hypogonadal, known to have different circulating concentrations of gonadotrophins. After 10 days the gels were recovered and processed for histology or the oocytes were recovered and their diameters measured and their ability to resume meiosis was determined. The growth of isolated primary follicles was positively correlated with the concentrations of circulating gonadotrophins in the recipient mice, but the numbers of oocytes recovered, the rate of oocyte growth and resumption of meiosis did not differ in the 3 types of recipient studied. This indicates that, in the conditions provided, oocyte growth was not related to the extent of follicular development. PMID- 1920301 TI - Effect of steroid- and inhibin-free ovine follicular fluid on ovarian follicles and ovarian hormone secretion. AB - Treatment of ewes with steroid-free ovine follicular fluid (oFF) during the follicular phase of the oestrous cycle results in the immediate inhibition of the ovarian secretion of oestradiol, inhibin and androgens. An experiment was conducted to determine whether this effect of oFF was due to inhibin, or to direct inhibition of ovarian function by other factors in oFF. Eight ewes in which the left ovary and vascular pedicle had been autotransplanted to a site in the neck were studied during the breeding season. Luteal regression was induced in all animals by injection of cloprostenol (100 micrograms i.m.; PG) on Day 10 of the luteal phase. The animals were divided into two groups (n = 4) and treated with either steroid-free oFF (oFF; 3 ml s.c.; 3.2 microgram p1-26 alpha inhibin/ml) or steroid-free oFF in which the inhibin content had been reduced by greater than 90% (IFoFF; 3 ml s.c.; 0.3 microgram p1-26 alpha inhibin/ml) by affinity chromatography, 24 and 36 h after PG. Samples of ovarian and jugular venous blood were collected at (i) intervals of 4 h from 16 h before until 120 h after PG and (ii) intervals of 10 min from 48 to 52 h after injection of PG to investigate the pattern of pulsatile secretion of ovarian hormones. All ewes had previously been monitored during a normal PG-induced follicular phase. Injection of oFF resulted in an increase (P less than 0.05) in the concentration of inhibin in jugular venous plasma and a profound (P less than 0.001) and prolonged decrease in the peripheral concentration of follicle-stimulating hormone (FSH). Injection of IFoFF had no significant effect on peripheral concentrations of inhibin or FSH in the first 24 h after treatment; thereafter inhibin concentrations fell (P less than 0.01) progressively until 40 h and then increased (P less than 0.01) until 72 h after treatment. In both treatment groups, however, within 24-36 h of treatment the concentration of FSH increased 5 10-fold (P less than 0.001) to a peak that occurred within 48-60 h and then declined to basal concentrations within 72-84 h of treatment. The concentration of luteinizing hormone (LH) in jugular venous plasma increased in both groups after treatment (P less than 0.01), although the rise after injection of oFF only started after 24 h. Thereafter, there was a progressive increase in the concentration of LH, peaks occurring 48-60 h after treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1920302 TI - Role of dihydrotestosterone in the control of sexual behaviour on castrated male sheep. AB - Wethers (at least 2 1/2 years after castration) were implanted with testosterone propionate (TP), oestradiol dipropionate (ODP), dihydrotestosterone, or a combination of dihydrotestosterone and ODP Silastic capsules. Active immunization against both oestradiol and oestrone or oestradiol only was used to negate effects of oestrogens produced by aromatization of TP. On exposure to oestrous ewes, immunization of wethers implanted with TP significantly (P less than 0.01) reduced all components of mating behaviour (except sniffing and Flehmen) to levels seen in untreated controls. The results support the conclusion that dihydrotestosterone potentiates the action of oestrogens, particularly as regards Flehmen, and has no action on its own within the central nervous system, while oestrogens do not restore mating activity to the same level as that following treatment with testosterone. PMID- 1920303 TI - Transport and storage of spermatozoa in the female reproductive tract of the brown marsupial mouse, Antechinus stuartii (Dasyuridae). AB - Female brown marsupial mice were mated and changes in the number and distribution of spermatozoa were assessed in several regions of the reproductive tract at 1, 2, 3, 7, 10, 14 and 18 days after mating. Approximately 40 x 10(3) spermatozoa/side were present in the female reproductive tract between Days 1 and 7 after a single mating. This had decreased (to approximately 9 x 10(3) spermatozoa/side) by Days 10 and 14 after mating; by Day 18 no spermatozoa were recovered. The maximum number of spermatozoa recorded in a female tract was approximately 72 x 10(3) spermatozoa/side (Day 5 female, death in laboratory) and the minimum recorded was approximately 2 x 10(3) spermatozoa/side on Day 2 after mating. Between Days 1 and 7 after mating most spermatozoa were located in the uterus and lower isthmus (isthmus 1) and spermatozoa were rarely found in the lateral vaginae. By 24 h after mating most spermatozoa (approximately 60%) were found in isthmus 1, but approximately 35% were still present in the uterus. Histological observations of the lower isthmus at this time showed that large numbers of spermatozoa were present in both the lumen of the duct and the sperm storage crypts which are located in this region. By Day 7 after mating approximately 91% of all spermatozoa in the female tract were in isthmus 1, most of these being confined to the sperm storage crypts. On Days 10 and 14 after mating almost all spermatozoa in the tract were in the crypt regions of isthmus 1 and on Day 18 degenerating spermatozoa were observed. No special orientation or association of spermatozoa in relation to crypt cells was observed. These results show that, although the number of spermatozoa inseminated is low by mammalian standards sperm transport in this species is extremely efficient and a large proportion of spermatozoa reaches the isthmus before ovulation (approximately 1 in 1 to 1 in 7). Several observations may explain the remarkable success of these low numbers of spermatozoa, including specializations of the reproductive tract which may have a directing effect on sperm movement and the special relationship which exists between spermatozoa and the oviducal environment which results in viable sperm storage. Recent observations suggest that an unusual sinusoidal mode of progressive motility observed in this species, may also influence the success of the low numbers of ejaculated spermatozoa. PMID- 1920304 TI - Relationship of progression of radiographic changes in hands and wrists, clinical features and HLA-DR antigens in rheumatoid arthritis. AB - One hundred and twelve hospital based outpatients with rheumatoid arthritis (mean duration +/- standard error, 10.7 +/- 0.9 years) were studied for radiological progression of the hands and wrists over a mean period of 26.5 +/- 0.5 months. The majority were taking slow acting antirheumatic drugs (SAARD). The rate of radiographic progression was positively and independently associated with the female sex (p less than 0.01), erythrocyte sedimentation rate (ESR, p less than 0.05) and HLA-DR1 (p less than 0.05). There was a negative association with HLA DR4 (p less than 0.05) but this was no longer significant after adjusting for ESR. There was no relationship between the rate of radiological progression and the presence of rheumatoid factor, rheumatoid nodules and duration of treatment with SAARD. PMID- 1920305 TI - Are the results of controlled clinical trials and observational studies of second line therapy in rheumatoid arthritis valid and generalizable as measures of rheumatoid arthritis outcome: analysis of 122 studies. AB - We studied 122 controlled clinical trials and observational studies of second line therapy that involved 16,071 patients. The mean disease duration was 7.61 years at study entry. Controlled clinical trials were inherently short term, and 90.5% of patients were followed for 1 year or less (mean 8.8 months). The mean followup of observational studies was 31 months. Outcome assessments that included functional measurements were rare in either study type, as were considerations of socioeconomic factors. Except for methotrexate, which was used longer, half of the studies indicated discontinuation of therapy after 1.5 years. Good retention rates in studies of 3 to 12 months were not representative of longterm results, but controlled clinical trials and observational studies were similar as to retention during the first treatment year. Observational studies following controlled clinical trials can yield important information about RA treatment effectiveness not available from controlled clinical trials alone. PMID- 1920306 TI - Auranofin treatment in early rheumatoid arthritis may postpone early retirement. Results from a 2-year double blind trial. AB - The effect of early vs delayed initiation of slow acting antirheumatic drug (SAARD) therapy on the ability to maintain regular work, was evaluated in 83 patients with early rheumatoid arthritis (RA) in a placebo controlled, double blind 24-month study. The estimated probability to maintain working ability was higher in the early treatment group, especially during the second study year. Predicting factors were age, type of work, degree of disability and number of swollen joints. Despite the difficulties in interpreting the results due to the complexity of the underlying socioeconomical and labor market situation, the study supports early treatment in RA with regard to the maintenance of normal life. PMID- 1920308 TI - The frequency of a common anti-DNA antibody idiotype (16/6) in different populations of patients with systemic lupus erythematosus. AB - The 16/6 anti-DNA idiotype (id) is a pathogenic idiotype first identified on a human hybridoma antibody derived from a patient with systemic lupus erythematosus (SLE). The SA-1 anti-DNA, which antibody was established in a similar fashion from a patient with polymyositis, also carries the 16/6 id, although it has a greater reactivity with dsDNA. The presence of the 16/6 id as defined by anti 16/6 and anti-SA-1 was determined in 3 distinct populations of patients with SLE: 502 Mexicans, 98 English (including Caucasians, West Indians, Chinese, Asians) and 93 Israelis. A similar prevalence (around 20%) of the 2 idiotypes was found, with a significant overlap. The latter finding was supported by a significant correlation noted between the prevalence of the 2 idiotypes (r = 0.58 p less than 0.001). Despite the fact that 16/6 antibody is most probably encoded by a germline gene, thus being genetically determined, no distinction in the prevalence of the ids could be detected between completely different populations of patients with SLE. This finding may support the independent pathogenic role ascribed to the 16/6 id. PMID- 1920307 TI - Diagnostic value of antibodies against ribosomal phosphoproteins. A cross sectional and longitudinal study. AB - Antibodies against ribosomal phosphoproteins (anti-P antibodies) are found in about 10% of patients with systemic lupus erythematosus (SLE). Using an ELISA with a synthetic peptide for screening and an immunoblotting technique as a confirmation test for detection of these antibodies, we found 16 positive patients among 946 sera sent to our reference laboratory for anti-DNA determination. All 12 patients on which we could obtain clinical data had clearcut SLE, fulfilling 6 ARA criteria on average. Skin symptoms were observed more frequently in anti-P positive than in anti-P negative patients with SLE. We also tested 56 sera from 54 patients with well defined SLE during monosymptomatic exacerbations and found an identical frequency of about 10% of anti-P antibodies in groups of patients with different types of exacerbation, including psychosis. A retrospective analysis of 9 patients followed 3-10 years showed that they all were already positive for anti-P at the onset of disease. In total these patients showed 15 major peaks in anti-P levels (defined as at least a 4-fold rise in titer in a period of 3 months). Five of the fluctuations in anti-P levels were paralleled by fluctuations in anti-DNA levels. In 6/15 cases, peaks of anti-P levels were accompanied by an exacerbation of SLE, but only 2 peaks of anti-P levels were already detectable before the onset of the exacerbation. In addition, 6 other exacerbations occurred in the absence of major anti-P rises in the preceding 3 months. Therefore, quantitative determinations of anti-P have at most a limited practical value in the followup of patients with SLE. PMID- 1920309 TI - AIDS and rheumatic manifestations in patients addicted to drugs. An analysis of 106 cases. AB - We evaluated the rheumatic manifestations in 106 patients with AIDS whose risk factor is intravenous drug addiction. All were intravenous drug addicts and carriers of the human immunodeficiency virus (HIV). Their average age was 28.36 years; 83 were men and 23 were women; 73 were in stage IV of the HIV infection; 12 were in stage III and 21 in stage II. Rheumatic manifestations were found in 21 patients (20%). Specifically, 13 had arthralgias/myalgias, 2 demonstrated oligoarthritis, 1 had tuberculous arthritis of the knee, and 1 patient showed systemic necrotizing vasculitis. Finally, 6 patients had a history of septic arthritis. There was an absence of the Reiter syndrome/reactive arthritis, a low frequency of symptoms of articular swelling, and the marked presence of histories of septic arthritis. The practices that lead to HIV infection may play a decisive role in the appearance of rheumatic manifestations in patients with AIDS, even more than the presence of the virus itself or the immunological alterations thereby produced. PMID- 1920310 TI - Detection of flexor tenosynovitis by magnetic resonance imaging: its relationship to diurnal variation of symptoms. AB - Fifteen patients with noninfectious arthritis and morning stiffness were examined clinically, and with magnetic resonance imaging (MRI) at the metacarpophalangeal level of one hand in the evening and early the following morning. Our purpose was to determine the prevalence of hand flexor tenosynovitis, and to look for diurnal changes in the swelling state of the flexor tendon sheaths as a possible cause for morning stiffness. MRI showed a higher prevalence of flexor tenosynovitis than clinically suspected by using the pinch test. We could not observe an increase in soft tissue swelling in the morning compared to the evening. PMID- 1920311 TI - The major rheumatoid factor crossreactive idiotype and IgA rheumatoid factor in juvenile rheumatoid arthritis. AB - One third of patients with juvenile rheumatoid arthritis (JRA) are seronegative for classic or hidden IgM rheumatoid factor (RF) yet express the major RF crossreactive idiotype (RCRI). We studied 60 children with JRA and 57 pediatric controls for IgA RF and RCRI expression to determine whether RCRI is associated with IgA RF in JRA. Twenty-one patients had IgA RF using rabbit or human IgG as substrate. Twenty-seven patients with JRA expressed high concentrations of RCRI in their sera. Only 9 of these had IgA RF. Eleven of the RCRI+ sera contained neither IgA RF nor classic or hidden IgM RF, and IgA RF was found in patients with all JRA onset subtypes. In JRA, RCRI may be expressed on either IgG RF or on parallel set antibodies without RF activity. PMID- 1920312 TI - Primary antiphospholipid syndrome: a report of two pediatric cases. AB - Two cases of primary antiphospholipid syndrome are described. A girl presented with myocardial infarction at the age of 6. afterward developed chorea, livedo reticularis, thrombocytopenia and circulating lupus anticoagulant (LAC). A boy, age 7, had an episode of intracranial hypertension and a deep venous thrombosis of a lower left limb, both recurrent in the following years. A high titer of IgG anticardiolipin antibodies (aCI) was detected. These observations suggest that both LAC and aCI tests should be performed in children with thromboembolic phenomena when the criteria for a definite autoimmune disease are lacking. PMID- 1920313 TI - Treatment of fulminant adult Still's disease with intravenous pulse methylprednisolone therapy. AB - We describe a patient with fulminant adult onset Still's disease and multiple organ involvement. The acute flare persisted despite high doses of prednisone but responded to megadose intravenous pulse methylprednisolone therapy. This treatment modality may be useful in temporizing severe multisystem exacerbations of adult Still's disease. PMID- 1920314 TI - Intraarticular corticosteroids possibly leading to local osteonecrosis and marrow fat induced synovitis. AB - We describe a woman with recurrent synovitis in one or both knees treated with intraarticular corticosteroid injections and two 6-day courses of methylprednisolone tablets. She later developed osteonecrosis of her distal femora and proximal tibiae. Her course was complicated by persistent synovitis associated with a large quantity of necrotic fat in the joint fluid. PMID- 1920315 TI - Aortitis and periaortic fibrosis. AB - A 45-year-old man presented with bilateral lower extremity claudication due to aortitis and periaortic fibrosis. This variety of aortitis has been described in the pathologic literature as chronic periaortitis, a subset of idiopathic retroperitoneal fibrosis. The association of this aortitis with abdominal aortic aneurysm has been described in the surgical literature as inflammatory abdominal aortic aneurysms. These entities are thought to be secondary to the same disease process. We review the possible etiology, diagnostic considerations, and management of these aortidites. PMID- 1920316 TI - Palpable purpura and uveitis precipitated by splenectomy in an atypical case of Cogan's syndrome. AB - A patient with a baffling multisystem illness developed uveitis and palpable purpura shortly after a splenectomy, leading to the diagnosis of vasculitis. Clearance by the mononuclear phagocyte system is a key factor determining the pathogenicity of circulating immune complexes, which are known to be the cause of some forms of vasculitis. The sudden appearance of uveitis and cutaneous vasculitis in an illness of many years' duration was probably a direct result of removal of the spleen. PMID- 1920318 TI - Rheumatoid arthritis is not associated with Kpn I polymorphism for T cell receptor C beta gene in HLA-DR4 subgroup. PMID- 1920317 TI - Sternoclavicular pustulotic osteitis (SAPHO). 20-year interval between skin and bone lesions. AB - In 2 cases of palmoplantar pustulosis, a 20-year interval was observed between the skin lesion and the bone involvement. In one case, the bone lesion came first. In the other a skin lesion was seen for 3 weeks without subsequent relapse. The 2 cases underline the multifaceted presentation of the condition for which we have coined the name synovitis acne pustulosis hyperostosis osteitis (SAPHO) syndrome. PMID- 1920319 TI - Salmonella septic arthritis presenting as reactive arthritis. PMID- 1920320 TI - Scheuermann's disease and septic spondylodiscitis. A coincidental association? PMID- 1920321 TI - Spondyloarthropathies in sub-Saharan Africa. PMID- 1920322 TI - Ovarian function in active AS. PMID- 1920323 TI - Golf scores as a measure of giant cell arteritis. PMID- 1920324 TI - Hypophosphatasemia, not hypophosphatasia. PMID- 1920325 TI - Clinical trials in rheumatoid arthritis under attack: are practice based observational studies the answer? PMID- 1920326 TI - Digital flexor tenosynovitis: diagnosis and clinical significance. PMID- 1920327 TI - Prophylaxis of nonsteroidal antiinflammatory drug gastropathy: a clinical opinion. PMID- 1920328 TI - Is misoprostol prophylaxis indicated for NSAID induced adverse gastrointestinal events? An epidemiologic opinion. PMID- 1920329 TI - Intraarticular progesterone inhibits 3H-dexamethasone binding to synovial cells from patients with rheumatoid arthritis. A study by dry radioautographic technique. AB - Glucocorticoids are known to exert their antiinflammatory effects through an interaction with specific hormone receptors. Progesterone is able to bind to these glucocorticoid receptors exerting either agonistic or antagonistic actions. We have reported that a single intraarticular injection of progesterone exerts a local antiinflammatory action in patients with rheumatoid arthritis (RA), suggesting an agonistic effect of progesterone on local glucocorticoid receptors. To corroborate this possible mechanism of action, we investigated the binding of 3H-dexamethasone to local glucocorticoid receptors in synovial tissue from 3 patients with active RA, before and 14 days after a single intraarticular injection of progesterone. Both cytoplasmic and nuclear 3H-dexamethasone binding sites were observed within synoviocytes, macrophages, fibroblasts, lymphocytes and endothelial cells. Dry radioautograms of biopsied synovial tissue demonstrated a marked decrease of 3H-dexamethasone binding following progesterone treatment in all patients (p less than 0.001 for each comparison). Although the number of cases is not large enough to draw definitive conclusions, our data confirm the marked anti-inflammatory effect of intraarticular progesterone and support the hypothesis of an agonistic effect of progesterone (or its metabolites) on glucocorticoid receptors. PMID- 1920330 TI - Relationship of self-efficacy to pain behavior. AB - Our purpose was to examine the effects of self-efficacy on the pain behaviors exhibited by patients with rheumatoid arthritis (RA). Seventy-two patients with RA were assessed using a standardized videotaping procedure for rating specific pain behaviors such as limps, facial grimaces, and guarded movements. Patients also completed questionnaires measuring self-efficacy and depression. Hierarchical regression was used to assess the relationship between self-efficacy and pain behavior after the effects of demographic characteristics and disease activity were statistically controlled. Higher self-efficacy was found to be related to fewer pain behaviors. In contrast, depression was found to be unrelated to pain behavior. Our results indicate that the pain behaviors that patients with RA exhibit are related to their self-efficacy, not solely to their disease activity. PMID- 1920331 TI - The effect of age on methotrexate efficacy and toxicity. AB - We studied the clinical course of 235 patients with rheumatoid arthritis (RA) receiving methotrexate (MTX) over a mean of 1.9 years. Both older (greater than 65 years) and younger (less than or equal to 65 years) patients demonstrated clinical improvement, but older patients had greater improvement in erythrocyte sedimentation rate and hemoglobin than younger patients. Most assessments of laboratory abnormalities and symptoms suggestive of toxicity did not differ between age groups. But more gastrointestinal complaints and pulmonary complaints were reported in older patients, associations that have been noted in older patients not treated with MTX as well. Our data indicate that treatment that includes MTX is effective in older patients with RA, and that older patients improve at least as much as younger. PMID- 1920332 TI - The efficacy and toxicity of a constant low dose of methotrexate as a treatment for intractable rheumatoid arthritis: an open prospective study. AB - Ninety-two patients with intractable rheumatoid arthritis (RA) participated in an open prospective study of the longterm efficacy and toxicity of methotrexate (MTX), administered orally at a constant dosage of 7.5 mg/week. Twenty-four patients (25%) had to be withdrawn from the study within the first 12 months because of inefficacy or adverse reactions with a fatal outcome in 2 patients. In the remaining 68 patients, the mean duration of therapy was 19 months. Sixty three of 92 patients (68%) experienced significant clinical improvement after one year, 23 (25%) were in clinical remission. Twenty-three of these patients initially responded well but relapsed after a median of 15 months of therapy. In 5 patients (5%) the disease activity remained status quo. Toxicity was noted at some time in 51 patients (54%), consisting of clinical side effects in 37 patients (40%) and biological abnormalities in 36 patients (39%), including 9 patients (10%) with blood and bone marrow toxicity, in whom renal function at start was normal. Two of these latter 9 patients had a fatal outcome because of an unexpected renal deterioration due to intercurrent disease. Thus, MTX at this constant low dose appears to be a temporarily valuable therapy for intractable RA. Careful monitoring is necessary in view of the potentially dangerous side effects. PMID- 1920333 TI - Should methotrexate be discontinued before elective orthopedic surgery in patients with rheumatoid arthritis? AB - To determine if methotrexate (MTX) contributes to early postoperative complications, we studied 38 patients with rheumatoid arthritis (RA) who underwent elective orthopedic surgery. There were 4 complications of prosthetic joint infection or wound dehiscence or infection among 19 procedures performed on patients who continued MTX until less than 4 weeks before surgery, compared to no complications among 34 procedures performed on patients who discontinued MTX 4 weeks before surgery or who were taking no remittive agent for 3 months before surgery (p less than 0.03, Fisher's exact, 2-tailed). No demographic, clinical, laboratory, nutritional, or intraoperative differences between the 2 groups were apparent, suggesting that MTX may play a role in early postoperative complications in patients with RA. A larger, prospective trial to study this issue is warranted. PMID- 1920334 TI - Rheumatoid arthritis identified in population based cross sectional studies: low prevalence of rheumatoid factor. AB - All 5 cross sectional population based studies which included evaluation of all subjects for both rheumatoid factor (RF) and rheumatoid arthritis (RA) were reviewed. RF was found in only 19-33% of individuals who met the 1958 ARA criteria for RA. Many individuals identified in these studies met criteria for only "probable" or "possible" RA according to the 1958 criteria, and might not meet the 1987 criteria. However, RF was found in only 26-60% of subjects who met criteria for "definite" RA in the studies that included this information. Population based studies of RA often have been interpreted as applicable to clinical RA patients, which may explain in part different views of RA as both a mild and a progressive disease. PMID- 1920336 TI - The influence of arterial compliance on diastolic blood pressure and its relation to cardiovascular events. AB - Reduction of arterial compliance leads to a higher systolic (SBP) and a lower diastolic blood pressure (DBP). The increasing occurrence of reduced arterial compliance is responsible for the steep increase in SBP after the age of 50 years and also for the constancy and later decline in DBP. Reduced arterial compliance will blur the relationship between mean arterial pressure and DBP. This may change the relationships between cardiovascular events and DBP. The possibility of non-causal co-existence of reduced compliance and atherosclerosis is discussed. Such a co-existence would markedly influence the relationship between cardiovascular events and DBP. Finally, the influence that reduced compliance might have on the shape of the relation between cardiovascular episodes and diastolic and systolic blood pressure is discussed. PMID- 1920335 TI - Reliability of grip strength, walking time and button test performed according to a standard protocol. AB - Excellent interobserver and intraobserver reliability (reproducibility) was seen for the grip strength, walking time and button test measures in 40 patients with rheumatoid arthritis (RA), when measurement was performed according to a standard protocol. Evidence of reliability, coupled with the observation that baseline measures predict longterm morbidity and mortality in individual patients, suggests that these measures might be more widely used in general rheumatologic care. PMID- 1920337 TI - Blood pressure changes as predictors of future mortality in the seven countries study. AB - Twelve cohorts of men aged 40-59 at entry, enrolled in six countries (Finland, The Netherlands, Italy, Yugoslavia, Greece and Japan), giving a total of 8,287 subjects, were examined for the measurement of cardiovascular risk factors and then followed-up for 20 years. Changes of systolic blood pressure (SBP) occurred over the first 10 years in 6,767 men and these values, computed by an integral like procedure (Delta-SBP), were used as possible predictors of fatal events recorded in the second 10 years of follow-up. Men who had a relative increase of SBP in the first 10 years showed an excess risk of death as compared with those who had a relative decrease of SBP, after adjustment for age and entry levels of SBP. Such relative risks were greater than 1 in the cohorts pooled within each of the six countries, ranging from 1.07 to 1.79 for all causes of death and from 1.12 to 2.15 for atherosclerotic cardiovascular disease deaths (coronary, stroke and peripheral atherosclerotic disease). The Cox model was solved using the same two end-points as dependent variables and, as coviariates, six risk factors measured at entry examination (age, cigarettes smoked per day, body mass index, serum cholesterol, physical activity at work and systolic blood pressure). By adding Delta-SBP the predictive power of the models was significantly improved and the coefficients of Delta-SBP proved to be statistically significant. PMID- 1920338 TI - Correlations between left ventricular mass and systolic blood pressure at rest and during maximal exercise in moderately hypertensive men. AB - We examined 87 men with moderate hypertension (diastolic blood pressure, DPB, greater than or equal to 95 and less than 110 mmHg) (mean age 45, range 22-64, years) with echocardiography and maximal ergometer bicycle test. Left ventricular mass index (LVMI) was calculated according to the Penn convention. Mean LVMI was 126 (60-210) g/m2. The maximal systolic blood pressure (SBP) during exercise was on average 217 (155-260) mmHg. Linear regression analysis revealed a significant correlation between LVMI and SBP at rest (r = 0.48, P less than 0.001) and during exercise (r = 0.39, P less than 0.001). Multiple regression analysis correcting for differences in age, cumulative work and cholesterol level revealed a significant correlation between LVMI and SBP at rest (t = 4.07, P less than 0.0001) and during exercise (t = 3.25, P = 0.002). Thus in patients with established, moderate hypertension exercise SBP is not more predictable for LVMI than is SBP at rest. PMID- 1920339 TI - The relationship of hyperinsulinaemia to the development of hypertension in type 2 diabetic patients and in non-diabetic subjects. AB - We have carried out a 5 year follow-up study of a group of 41 originally normotensive (BP less than 160/95 mmHg) newly diagnosed Type 2 (non-insulin dependent) diabetic patients (26 men, 15 women) and 86 non-diabetic subjects (39 men, 47 women) to assess the predictive value of serum insulin levels with regard to the development of hypertension. Hypertension (BP greater than 160/95 mmHg and/or drug treatment) developed in 14% of diabetic patients and 10% of non diabetic subjects (NS). The baseline postglucose insulin levels tended to be higher in those diabetic and non-diabetic subjects who developed hypertension during the 5 year follow-up than in those who remained normotensive, and in non diabetic subjects the differences were statistically significant after adjustment for age, sex and body mass index for the baseline 1 hour serum insulin (104 +/- 18 vs. 68 +/- 5 mU/l; P less than 0.05) and area under the insulin curve (138 +/- 34 vs. 85 +/- 8 mU/l.h, P less than 0.05). Both diabetic and non-diabetic subjects who developed hypertension showed elevated total- and VLDL-triglycerides at baseline compared with those subjects who remained normotensive during the follow-up. In conclusion, the results support the hypothesis that hyperinsulinaemia or insulin resistance may play a role in the pathogenesis of hypertension. PMID- 1920341 TI - Does treated essential hypertension result in renal impairment? A cohort study. AB - To determine how frequently essential hypertension results in significant renal impairment we undertook a follow-up study of 176 patients with well documented essential hypertension first seen in 1975-1977. Six patients were Asian, two Negro, and the remainder Europid. Follow-up was achieved in 92% of the cohort at five years and in 87% at 12-14 years. At five years 13 (7%) patients had moved away or were lost, and 15 (9%) patients had died (11 cardiovascular deaths). Treated blood pressure was greater than 160/95 mmHg in 60/148 patients and greater than 200/100 mmHg in 16 patients. Despite this, no significant change in serum creatinine was detected in the group as a whole. Increments in serum creatinine of at least 35 mumol/l occurred in six patients. Over the ensuing 6-9 years serum creatinine had returned to normal in three of these patients and stabilized in two; the sixth patient died from myocardial infarction. No patient reached end-stage renal failure. We conclude that progressive deterioration in renal function in essential hypertension is rarely a significant problem in Caucasian patients. A decline in renal function should prompt a search for underlying primary renal disease. PMID- 1920340 TI - Albuminuria induced by exercise in hypertensive type I and type II diabetic patients: a randomised, double-blind study on the effects of acute administration of captopril and nifedipine. AB - Physical exercise can increase urinary albumin excretion rate (UAER) in diabetic patients without microalbuminuria at rest (stage II diabetic nephropathy) or with baseline microalbuminuria (stage III diabetic nephropathy). The aim of this study was to compare the acute effects of captopril, an ACE inhibitor, and nifedipine, a calcium channel blocker, on exercise-induced microalbuminuria in hypertensive insulin-dependent (Type I) and non-insulin-dependent (Type II) diabetic patients with early stage nephropathy. Non-obese diabetic patients, 13 Type I (7 with stage II and 6 with stage III nephropathy) and 14 Type II (6 with stage II and 8 with stage III nephropathy), with hypertension, WHO stages I-II, underwent five submaximal cycloergometric tests: the first two in basal conditions, the other three after 24 hour administration of captopril (25 mg twice daily), placebo (1 tab twice daily) or nifedipine AR (20 mg twice daily) according to a randomised, double-blind design. Acute administration of both captopril and nifedipine was able to reduce exercise-induced microalbuminuria in hypertensive Type I and Type II diabetic patients regardless of the stage of their nephropathy. Captopril reduced systolic blood pressure less than nifedipine, in both Type I and Type II diabetics, but was more effective than nifedipine in blunting exercise-induced microalbuminuria, especially in Type I diabetics. PMID- 1920342 TI - Renin profile, race, and antihypertensive efficacy with atenolol and labetalol. AB - In this randomised double-blind parallel study, we compared the efficacy of labetalol and atenolol in a group of black (n = 33) and white (n = 34) hypertensives with uncomplicated essential hypertension after obtaining pretreatment renin profiles. After single-blind placebo (14-21 days), patients with standing diastolic BP between 105-119 mmHg were randomised to receive either labetalol (100-800 mg twice daily) or atenolol (50-100 mg once daily) to achieve a DBP less than 90 mmHg. Dosage titration occurred at weekly intervals for labetalol and biweekly for atenolol. The supine BP decrease with atenolol was 18/-14 vs. -6/-6 mmHg in whites vs. blacks respectively. With labetalol, it was 13/-12 in whites and -2/-7 mmHg in blacks. Standing BPs were: -19/-14 vs. -4/-5, whites vs. blacks with atenolol and -17/-17 vs. -19/-9 mmHg with labetalol. Neither labetalol nor atenolol was as effective in black compared with white hypertensives. The atenolol but not labetalol BP response was positively correlated with pretreatment renin values. PMID- 1920343 TI - Effect of atenolol or enalapril on diurnal changes of blood pressure in Japanese mild to moderate hypertensives: a double-blind, randomised, crossover trial. AB - This randomised, double-blind, crossover study compared enalapril 5 mg, and atenolol 50 mg, each dosed once daily for 4 weeks, and investigated casual and diurnal BP changes using 24 hour ambulatory BP monitoring. Both atenolol and enalapril satisfactorily lowered BP during the day and no excessive falls occurred at night. The tendency for BP to increase during the day and decrease at night was maintained during both active periods. Pulse rate was reduced only by atenolol throughout 24 hours. The BP increase observed 2 hours after rising in the morning was suppressed by atenolol but not by enalapril. Both drugs reduced the rates of systolic (greater than or equal to 160 mmHg) and diastolic (greater than or equal to 95 mmHg) BP increases to half of those during placebo. The frequency with which diastolic BP increased above these limits was less during the atenolol period. The difference in BP between a hospital casual reading and the mean 24 hour ambulatory reading was reduced only by atenolol. Furthermore, only atenolol suppressed the BP and pulse rate increases on exercise. PMID- 1920345 TI - Evaluation of the SpaceLabs 90202 non-invasive ambulatory recorder according to the AAMI Standard and BHS criteria. AB - The SpaceLabs 90202, a non-invasive ambulatory blood pressure recorder for the measurement of 24 hr blood pressure, was assessed according to the standard of the Association for the Advancement of Medical Instrumentation (AAMI) and the grading criteria of the British Hypertension Society (BHS) protocol were applied to the results. Two observers measured BP simultaneously in the same arm with the SpaceLabs 90202 and a standard mercury sphygmomanometer at 4 mmHg deflation steps in 85 subjects [age range 22-79 years, BP range 96-212 mmHg (systolic) and 52-134 mmHg (diastolic)]. The mean difference was -2 +/- 5 mmHg (systolic) and -2 +/- 5 mmHg (diastolic). The mean difference (+/- SD) between observers was 1 +/- 3 (systolic) and -2 +/- 3 (diastolic). The SpaceLabs 90202 fulfills the criteria of the AAMI standard (5 +/- 8 mmHg) and a B grading for both systolic and diastolic pressure is achieved with the BHS criteria. PMID- 1920344 TI - Nicardipine as antihypertensive monotherapy: positive effects on quality of life. AB - The effects of nicardipine and propranolol on patients' quality of life were compared during a double-blind, multicentre, parallel, randomised study of hypertension therapy. After a placebo run-in period, the doses for each patient were successfully titrated to reduce supine diastolic blood pressure to less than 90 mmHg with either nicardipine 60 or 90 mg/day (123 patients) or with propranolol 90-240 mg/day (120 patients). Both drugs demonstrated similar efficacy in reducing systolic and diastolic blood pressure. Total duration of therapy ranged from 6-12 weeks. The Nottingham Health Profile questionnaire was used to assess the effect of each treatment on the patients' quality of life. The overall quality of life score for patients on nicardipine showed a tendency toward improvement, while for those on propranolol, the trend was toward overall worsening. The differences between the two treatment groups were statistically significant for males (P = 0.02). The analysis of the separate components of this evaluation demonstrated that physical mobility was reported to be decreased more for the propranolol-treated patients than for the nicardipine-treated patients (P = 0.02). In contrast to the propranolol-treated patients, the nicardipine-treated patients reported improvements for sleep, social life, work, sex life, and for activities related to hobbies and interests. A second questionnaire was used to assess the effects of the therapies on work productivity. Among those patients who worked for pay, more patients treated with propranolol than those treated with nicardipine rated themselves as less productive at work (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920347 TI - Rhythm disturbances in essential hypertension. PMID- 1920346 TI - Alcohol and hypertension--implications for management. A consensus statement by the World Hypertension League. AB - The World Hypertension League (WHL) is an association of antihypertensive leagues, hypertension societies, committees and other national bodies whose aim is to control hypertension in populations. The present paper is the fourth in a series of 'In the Focus Statements' on topics selected for their practical importance to the management of hypertension, addressed to practising physicians. Like the earlier papers, it has been repeatedly and extensively discussed by the representatives of WHL's member organizations' and accepted as a consensus document. PMID- 1920348 TI - NMR studies of molecular complexes as a tool in drug design. PMID- 1920350 TI - Muscarinic receptor binding profile of para-substituted caramiphen analogues. AB - Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent parameters such as Hammett's sigma or Hansch's pi values. It is felt this could be determined initially with only four properly chosen substituents. In this approach, substituents were chosen which have an extreme value for sigma and for pi, in a positive and negative direction, in all combinations. The substituents chosen for examination were amino (-sigma, -pi); 1-pyrrolidinyl ( sigma, +pi); 1-tetrazolyl (+sigma, -pi), and iodo (+sigma, +pi). It was determined in this research that caramiphen binds with high affinity (Ki = 1.2 nM) and is selective for the M1 over M2 muscarinic receptor subtype (26-fold). An examination of para-substitution reveals that compounds with electron-withdrawing (+sigma) substituents showed M1 selectivity, while the derivatives with electron donating groups (-sigma) were nonselective in the binding assays. On the basis of this finding, the nitro and cyano derivatives were prepared and found to be M1 selective. The + sigma derivatives showed a decrease in M2 affinity while the p nitro and p-iodo derivatives retained approximately equal affinity as caramiphen for the M1 site. The nitro- and iodocaramiphen derivatives were as potent (M1, Ki = 5.52 and 2.11 nM, respectively) and showed a greater selectivity of M1 over M2 binding than the M1 prototypical agent pirenzepine (M1, Ki = 5.21 nM). PMID- 1920349 TI - Structure-activity studies of antitumor agents based on pyrrolo[1,2 a]benzimidazoles: new reductive alkylating DNA cleaving agents. AB - Described herein are structure-activity studies of new antitumor agents based on the pyrrolo[1,2-a]benzimidazole (PBI) ring system. These compounds were designed as new DNA cross-linkers mimicking the mitomycin antitumor agents. Actually, the PBI derivatives were found to have anthracycline-like features: (i) shared cross resistance with doxorubicin in a human myeloma line, (ii) cardiotoxicity, and (iii) excellent DNA strand cleaving capability. The DNA strand cleavage is thought to result from reductive alkylation of DNA followed by the generation of reactive oxygen radicals. The best antitumor agent studied is 6-N-aziridinyl-3 hydroxy-7-methyl-2,3-dihydro-1H-pyrrolo- [1,2-a]benzimidazole-5,8-dione 3-acetate (PBI-A), which possesses nanomolar IC50 values against various human ovarian and colon cancer cell lines. PMID- 1920351 TI - Synthesis and muscarinic cholinergic receptor affinities of 3-quinuclidinyl alpha (alkoxyalkyl)-alpha-aryl-alpha-hydroxyacetates. AB - Seven analogues of 3-quinuclidinyl benzilate (QNB) in which one phenyl ring was replaced by an alkoxyalkyl moiety were synthesized and their affinities for the muscarinic cholinergic receptor determined. An oxygen in the beta-position of the moiety was not well-tolerated. By contrast, an oxygen in the gamma-position did not change the affinity for the muscarinic receptor. However, when a bromine was placed on the remaining phenyl ring, the affinity was significantly reduced in striking contrast to results obtained on halogenation of QNB. PMID- 1920352 TI - Synthesis, calcium-channel-blocking activity, and antihypertensive activity of 4 (diarylmethyl)-1-[3-(aryloxy)propyl]piperidines and structurally related compounds. AB - A series of 4-(diarylmethyl)-1-[3-(aryloxy)propyl]piperidines and structurally related compounds were synthesized as calcium-channel blockers and antihypertensive agents. Compounds were evaluated for calcium-channel-blocking activity by determining their ability to antagonize calcium-induced contractions of isolated rabbit aortic strips. The most potent compounds were those with fluoro substituents in the 3- and/or 4-positions of both rings of the diphenylmethyl group. Bis(4-fluorophenyl)acetonitrile analogue 79 was similar in potency to bis(4-fluorophenyl)methyl compound 1. The methylene analogue of 1 (78) and derivatives of 1 that contained a hydroxyl (76), carbamoyl (80), amino (81), or acetamido (82) substituent on the methyl group were less potent. In most cases, substituents on the phenoxy ring, changes in the distance between the aryloxy group and the piperidine nitrogen, and the substitution of S, N(CH3), or CH2 for the oxygen atom of the aryloxy group had only a small to moderate effect on the potency. The best compounds in this series were more potent than verapamil, diltiazem, flunarizine, and lidoflazine, but were less potent than nifedipine. Compounds were evaluated for antihypertensive activity in spontaneously hypertensive rats (SHR) at an oral dose of 30 mg/kg. Of the 55 compounds tested, only nine produced a statistically significant (p less than 0.05) reduction in blood pressure greater than 20%; all of these compounds had fluoro substituents in both rings of the diphenylmethyl group. One of the most active compounds in the SHR at 30 mg/kg was 1-[4-[3-[4-[bis(3,4 difluorophenyl)methyl]-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone (63), which produced a 35% reduction in blood pressure and was similar in activity to nifedipine. At lower doses, however, 4-[bis(4-fluorophenyl)methyl]-1-[3-(4 chlorophenoxy)propyl]piperidine (93) was one of the most effective antihypertensive agents, producing reductions in blood pressure of 17 and 11% at oral doses of 10 and 3 mg/kg, respectively; 63 was inactive at 10 mg/kg. PMID- 1920353 TI - Peptide derivatives specific for a Plasmodium falciparum proteinase inhibit the human erythrocyte invasion by merozoites. AB - A specific proteinase of P. falciparum merozoites has been detected by using hydrosoluble fluorogenic peptidic substrates synthesized by classical peptide chemistry; their N-terminal end was acylated by a gluconoyl group that protects them from aminopeptidase degradation and increases their hydrosolubility, and their carboxylic end was substituted by a 3-amino-9-ethylcarbazole group. The sequence Val-Leu-Gly-Lys was found to be the most specific substrate. On this basis, reversible peptidic inhibitors were synthesized by substituting the C terminal lysyl residue, at the proteolytic site, by different alkylamines and amino alcohols. The activity of these compounds, studied on the P. falciparum proteinase and in in vitro cultures, strongly suggests a specific effect of this peptidic sequence on the reinvasion process. The peptidic inhibitors do not impair the release of merozoites from schizonts, but selectively inhibit the invasion step leading to the formation of rings. Although the natural target of this enzyme is not yet known, these specific peptide inhibitors could lead to a new antimalarial approach. PMID- 1920354 TI - An investigation of angiotensin II agonist and antagonist analogues with 5,5 dimethylthiazolidine-4-carboxylic acid and other constrained amino acids. AB - To probe the receptor-bound conformational requirements of angiotensin II (ANG II) octapeptide agonists and antagonists, the synthesis and biological activities of [Sar1]ANG II agonist and [Sar1,X8]ANG II antagonist analogues (X8 = Ile, D Phe, or Aib) bearing conformational constraints in positions 3, 5, and 7 were investigated and compared with previous literature efforts. The conformational constraints that were examined include Pro, Dtc (5,5-dimethylthiazolidine-4 carboxylic acid), Aib, Cle, (NMe)Ala, (NMe)Ile, and the lactam modification, L,L lactam-Phe, previously described by Freidinger et al. (J. Org. Chem. 1982, 47, 104-109). Both [Sar1,(NMe)Ala3 and Pro3]ANG II retained agonist activity, while only [Sar1,(NMe)Ala3,Ile8]ANG II retained antagonist activity. [Sar1,Dtc5]ANG II displayed superior agonist activity, while both [Sar1,Dtc5 and Cle5,Ile8] ANG II displayed superior antagonist activity. In contrast to position 5, Dtc7 substitution for Pro7 of either [Sar1]ANG II or [Sar1,Ile8]ANG II gave analogues with reduced activities. These results are consistent with the hypothesis that conformations of [Sar1]ANG II and [Sar1,Ile8]ANG II containing a C7 conformation in position 7 are preferred for both ANG II agonist and antagonist activity. Incorporation of the L,L-lactam-Phe modification into [Sar1]ANG II gives a pure ANG II antagonist (pA2 8.3), comparable to saralasin (pA2 8.6). In positions 3, 5, and 7 the conformational requirements for the ANG II agonist [Sar1]ANG II and the ANG II antagonist [Sar1,Ile8]ANG II may be different. Individual substitution of (NMe)Ala3, Dtc5, D-Phe8 and Aib8 [[Sar1,Aib8]ANG II: Khosla et al. J. Med. Chem. 1977, 20, 1051-1055] into [Sar1,Ile8]ANG II gives analogues that retain antagonist activity. Multiple substitutions of these types of residues into [Sar1,Ile8]ANG II gives analogue 45 [Sar1,(NMe)Ala3,Dtc5,Aib8]ANG II, 46 [Sar1(NMe)Ala3,D-Phe8]AII, and 47 [Sar1,Dtc5,D-Phe8]AII, which display considerably reduced antagonist activity. In ANG II antagonists the construction of highly constrained analogues may not be possible by the additive substitution of "preferred" constrained amino acids into a single analogue. PMID- 1920355 TI - Synthesis and antitumor properties of activated cyclophosphamide analogues. AB - A series of 5- and 6-substituted cyclophosphamide analogues has been prepared, and their 31P NMR kinetics of phosphoramide mustard (PDA) release and in vitro and in vivo cytotoxicity have been evaluated. cis-4-Hydroxy-5 methoxycyclophosphamide equilibrated very slowly and to a minor extent with the ring-opened aldophosphamide analogues in aqueous buffer; release of PDA was observed to a minor extent and only at high (1 M) buffer concentrations. This analogue was essentially inactive in vitro against L1210 and P388 leukemia cells. 6-Phenylcyclophosphamide and its 4-hydroperoxy derivative were potent inhibitors of blood acetylcholinesterase and were lethal at therapeutic doses in mice. In contrast, 4-hydroperoxy-6-(4-pyridyl)cyclophosphamide did not inhibit acetylcholinesterase and showed significant antitumor activity in vitro and in vivo against both wild-type and cyclophosphamide-resistant L1210 leukemia. The 4 hydroperoxy-6-arylcyclophosphamides were generally active in vitro against both wild-type and cyclophosphamide-resistant L1210 and P388 cells, and several analogues showed significant activity in vivo. Surprisingly, there was no correlation between antitumor activity in vitro and the rate of PDA release in aqueous buffer. Several compounds that showed essentially no release of PDA in aqueous buffer over several hours were highly cytotoxic to leukemia cells following a 1-h exposure in vitro. These results show that activated cyclophosphamide analogues substituted at the 6-position are not cross-resistant in these leukemia cell lines, and that a specific intracellular activation mechanism may be catalyzing PDA release in these analogues. PMID- 1920356 TI - Synthesis, activation, and cytotoxicity of aldophosphamide analogues. AB - A series of perhydrooxazine analogues of aldophosphamide has been prepared, and their 31P NMR kinetics and in vitro cytotoxicity have been evaluated. These compounds were developed on the basis of the idea that ring opening and tautomerization to an enamine intermediate might provide a mechanistic alternative to the beta-elimination reaction for release of phosphoramide mustard. The 4,4,6-trimethyltetrahydro-1,3-oxazine moiety was selected on the basis of its rapid rate of iminium ion generation and relatively slow rate of hydrolysis. These analogues underwent phosphorodiamidate release by three distinct mechanisms: hydrolysis to aldophosphamide and subsequent beta elimination; cyclization to produce the 4-hydroxycyclophosphamides, which release phosphorodiamidate by ring opening and elimination; and tautomerization to the enamine with rapid expulsion of phosphorodiamidate. Kinetic studies demonstrated that hydrolysis to the aldehyde contributed minimally to the overall activation process and that the enamine pathway represented the major route of activation. For those analogues that could undergo cyclization, this pathway competed effectively with enamine release, and these analogues were essentially equivalent to their 4-hydroxycyclophosphamide counterparts in cytotoxicity. A series of tetra-N-substituted phosphorodiamidates that cannot undergo cyclization was prepared to explore the effects of cyclization on the cytotoxicity of these analogues. The tetrakis(chloroethyl)phosphorodiamidates were highly potent in vitro against both cyclophosphamide-sensitive and -resistant L1210 and P388 cell lines, and one of these analogues had significant antitumor activity against L1210 leukemia in vivo. These results demonstrate that the enamine mechanism provides a viable pathway for delivery of phosphorodiamidates and that this approach can be used to deliver phosphorodiamidates that are non-cross-resistant in cyclophosphamide-resistant cell lines. PMID- 1920357 TI - Analogues of oxybutynin. Synthesis and antimuscarinic and bladder activity of some substituted 7-amino-1-hydroxy-5-heptyn-2-ones and related compounds. AB - Oxybutynin chloride [4-(diethylamino)-2-butynyl alpha-cyclohexyl-alpha hydroxybenzeneacetate hydrochloride, Ditropan] is widely used for the relief of symptoms in neurogenic bladder. This is a result of its combined anticholinergic, antispasmodic, and local anesthetic activities. In a study directed toward development of agents possessing the beneficial properties of oxybutynin, but having a longer duration of action, a series of metabolically more stable keto analogues of the parent ester, i.e. substituted 7-amino-1-hydroxy-5-heptyn-2-ones along with some analogues and derivatives, was prepared and evaluated for in vitro and in vivo antimuscarinic action in guinea pig preparations. Several members of the series were potent antimuscarinics having a longer duration of activity than that of oxybutynin in a guinea pig cystometrogram model. On the basis of its in vitro and in vivo antimuscarinic activity, coupled with a 5-fold greater duration of action than that of oxybutynin, 1-cyclobutyl-7 (dimethylamino)-1-hydroxy-1-phenyl-5-heptyn-2-one (14b) was selected for clinical evaluation. PMID- 1920358 TI - 3-Methyl-2H-1-benzopyran potassium channel activators. AB - By aldol condensation of 4-chromanones with paraformaldehyde, 3 alkylenechromanones 10 were obtained which gave 3-alkylchromenes following reduction and dehydration. Subsequent 3-chloroperbenzoic acid oxidation produced the versatile epoxide intermediates 15, from which 3,4-epoxy-3,4-dihydro-2,2,3 trimethyl-2H-1-benzopyran-6-carbonitrile (15a) was resolved into its enantiomers by entrainment. In addition to the methyl group, the benzyl, alkyloxymethyl, and 2-nitroethyl residues could be introduced in the 3-position. Treatment of 15a with 2-pyridone simultaneously gave N- and O-substituted products 19a and 20. 19a easily gave 4-(1,2-dihydro-2-oxo-1-pyridyl)chromene 21 by treatment with base. The corresponding pyrrolidinone compounds 26 and 27 were obtained by a slightly modified procedure. Reaction with 2,4-dihydroxypyridine or 3,6-pyridazinediol resulted in the exclusive formation of 4-(heterocyclyloxy)chromanols (31 and 32). Treatment of 15a with 3-amino-6-pyridazinol gave 4-(3-amino-1,6-dihydro-6-oxo-1 pyridazinyl)chromanol derivative 34 lacking an NH bridge. This could be established after methylation of the ring-nitrogen atom (----35). Trans configurated 3-methyl-4-pyridone compound 36 was obtained by addition of methyllithium to chromene 3. Hyperpolarizing and antispasmodic or relaxing effects of the compounds were determined in organ bath studies using pig coronary arteries precontracted with acetylcholine or rabbit main pulmonary arteries precontracted with noradrenaline. In the 3-methyl series the classical pyridone and pyrrolidinone structures (9, 21, 26, 27) were only weakly active or inactive, but the corresponding 4-(heterocyclyloxy) and 4-(heterocyclylamino) derivatives (31, 32, 35) were even more potent than the demethyl analogues. In conformation/activity investigations it was found that the activity of the 4 substituted benzopyran derivatives seems to be dependent on the relative orientation of their ring systems. PMID- 1920359 TI - Topically active carbonic anhydrase inhibitors. 4. [(Hydroxyalkyl)sulfonyl]benzene and [(hydroxyalkyl)sulfonyl]thiophenesulfonamides. AB - For several decades a tantalizing goal for the treatment of primary open-angle glaucoma has been the development of a topically active carbonic anhydrase inhibitor. Recent results from several research groups indicate that considerable progress has been made toward this objective. In this report, we present the design and synthesis of (hydroxyalkyl)sulfonyl-substituted benzene- and thiophenesulfonamides. These compounds exhibit inhibition of carbonic anhydrase II in the nanomolar range and lower intraocular pressure in the alpha chymotrypsinized rabbit model of ocular hypertension after topical instillation. PMID- 1920360 TI - Nonpeptidic angiotensin II antagonists: synthesis and in vitro activity of a series of novel naphthalene and tetrahydronaphthalene derivatives. AB - Starting from the structure of the novel nonpeptidic angiotensin II antagonist DuP 753, a series of more rigid analogues was prepared by replacing the biphenyl part of DuP 753 with a naphthalene ring. Five different regioisomers (compounds 6a-e) were synthesized, and receptor binding in rat smooth muscle cell preparations as well as inhibition of angiotensin II induced contraction of rabbit aortic rings was measured and the order of potency was compared with predictions made on the basis of a molecular modeling study. In good agreement with the predictions, the 2,6-substituted regioisomer 6d and its analogue 7 (isomeric at the imidazole substituent) were found to be most potent, but were still weaker than DuP 753. Tetrahydronaphthalene derivatives with and without an additional methyl group in the alpha-position to the acidic function and with this same 2,6-substitution pattern (compounds listed in Table III) were then prepared with the expectation of getting a further increase in potency. Whereas the carboxylic acid derivatives 13a,b showed activity in the expected potency range, surprisingly no further potency increase was observed after replacement of the carboxylic acid function by a tetrazole (compounds 18a,b). These results may indicate that the compounds do not bind to the AT1 receptor in the same way as DuP 753. PMID- 1920361 TI - Development of a small RGD peptide fibrinogen receptor antagonist with potent antiaggregatory activity in vitro. AB - The development of potent antithrombotic agents from the fibrinogen platelet receptor binding sequences Fg-alpha 572-575 -Arg-Gly-Asp-Ser- and Fg-gamma 400 411 -HHLGGAKQAGDV, believed to be a cryptic RGD-type sequence, is described. The tetrapeptide Ac-RGDS-NH2 itself is capable of inhibiting platelet aggregation in vitro at high concentrations, IC50 91.3 +/- 0.1 microM [in vitro antiaggregatory activity employing dog platelet rich plasma (PRP)/ADP], due to low platelet fibrinogen receptor affinity, Ki 2.9 +/- 1.9 microM (purified, reconstituted human platelet GPIIb/IIIa), relative to fibrinogen, Ki 38.0 +/- 6.0 nM. The peptide is also unstable to plasma, suffering total loss of in vitro activity upon incubation in PRP for 3 h (T1/2 90 min). Only modest improvements in potency were achieved with linear analogues of Ac-RGDS-NH2, while dramatic results were achieved with cyclic analogues, culminating in the cyclic disulfide Ac-cyclo-S,S [Cys-(N alpha-Me)Arg-Gly-Asp-Pen]-NH2 (SK&F 106760) with improved plasma stability (100% activity after 3 h), affinity (Ki 58 +/- 20 nM purified human receptor), and potency (IC50 0.36 +/- 0.4 microM dog PRP/ADP). The affinity of this peptide is 2 orders of magnitude greater than that of Ac-RGDS-NH2. The affinity of the analogue is also comparable to fibrinogen. This peptide constitutes a first potent small peptide entry into the class of novel antithrombotic agents called fibrinogen receptor antagonists. PMID- 1920362 TI - Synthesis and evaluation of some nitrobenzenesulfonamides containing nitroisopropyl and (ureidooxy)methyl groups as novel hypoxic cell selective cytotoxic agents. AB - Basic nitrobenzenesulfonamides containing nitroisopropyl and (ureidooxy)methyl groups were prepared and evaluated as novel hypoxic cell selective cytotoxic agents. In vitro, N-(2-aminoethyl)-N-methyl-3-nitro-4-(1-methyl-1 nitroethyl)benzene sulfonamide hydrochloride (11) proved to be preferentially toxic to hypoxic EMT6 mammary carcinoma cells. At 1 mM concentration in vitro, 11 reduced the surviving fraction of these hypoxic cells to 3 x 10(-3) with no effect on aerobic cells. In radiation experiments, 11 appeared to function as a hypoxic cell radiosensitizer as well as a selective cytotoxic agent. However, administration of 11 at 200 mg/kg ip or 100 mg/kg iv to BALB/c mice implanted with solid EMT6 tumors produced no evidence of significant in vivo cytotoxic or radiosensitizing activity. N-Methyl-N-[2-(methylamino)ethyl]-3-nitro-4- [(ureidooxy)methyl]benzenesulfonamide hydrochloride (20) showed slight differential toxicity toward EMT6 cells at 3 mM concentration and radiosensitizing activity comparable to misonidazole at 1 mM concentration. PMID- 1920363 TI - Monovalent sialosides that bind tightly to influenza A virus. PMID- 1920364 TI - Peptide to glycopeptide: glycosylated oligopeptide renin inhibitors with attenuated in vivo clearance properties. PMID- 1920365 TI - [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane: high-affinity SPECT radiotracer of monoamine reuptake sites in brain. PMID- 1920367 TI - Reproductive behaviour of families segregating for Cooley's anaemia before and after the availability of prenatal diagnosis. AB - The reproductive behaviour of couples with heterozygous beta thalassaemia, with at least one affected child, was investigated for the period 1955 to 1984 and was compared to the behaviour of control couples matched for age, age at marriage, and presence of at least one child. The comparisons were made as a function of knowledge of the risk and availability of prenatal diagnosis and abortion. It was found that the couples segregating for Cooley's anaemia, before knowledge of the risk, had a higher reproductive rate than that of control couples. Knowledge of the genetic risk had a different effect on reproductive behaviour in the 1950s from that in later years. The difference was attributed both to the influence of cultural factors and to technical, therapeutic, and diagnostic advances. PMID- 1920368 TI - Single maxillary central incisor in a girl with del(18p) syndrome. AB - We present a girl with del(18p) syndrome and a single maxillary central incisor; she is only the second patient in whom this association has been reported. PMID- 1920366 TI - Immunohistochemical studies show truncated dystrophins in the myotubes of three fetuses at risk for Duchenne muscular dystrophy. AB - We have performed immunohistochemical studies on muscle tissue of three 12 week old fetuses at risk for DMD, using antisera directed against regions located NH2 proximally and centrally in the rod shaped spectrin-like domain and against the COOH-terminus of dystrophin. All three fetuses had a family history of DMD. Truncated dystrophins were identified in all three cases by a positive reaction with the NH2-proximal antibody, different reactions with the central antibody, and a negative reaction with the COOH-terminal antibody. These data indicate that a panel of antibodies would, in principle, permit 'immunological' mapping of dystrophin mutations. This is diagnostically important in the 35% of families where no mutation is detectable at the DNA level. Secondly, by using this mapping technique it may also become possible to identify the at risk haplotype when DNA analysis is not informative. This may be of great value in DMD carrier detection. PMID- 1920370 TI - De novo ring chromosome 3: a new case with a mild phenotype. AB - We report an 18 year old female with a de novo ring chromosome 3 found after investigation for short stature. Her karyotype was interpreted as 46,XX, r(3)(p26.2q29). Her phenotype is milder than previously reported cases and illustrates the mild end of the spectrum of the ring chromosome 3 phenotype. PMID- 1920369 TI - Interstitial deletion of chromosome 13: prognosis and adult phenotype. AB - A de novo interstitial deletion of chromosome 13 (46,XY,del(13)(pter--- q14.3::q22.3----qter] is described in a 22 year old man with severe mental retardation, poor language development, low set ears, hypertelorism, broad nasal bridge, short hands and fingers, and a history of swallowing disorder in childhood with subsequent dyspepsia. The dysmorphic features did not become evident until later childhood, supporting the view that karyotyping should be performed routinely in all children with developmental delay. PMID- 1920371 TI - De novo interstitial deletion of 1p (pter----p34.1::p32.3----qter). AB - We report a case of a 9 month old girl with a de novo interstitial deletion of 1p, karyotype 46,XX, del(1)(pter----p34.1::p32.3----qter). She had dysmorphic features including upward slanting palpebral fissures, a bulbous nose, a long philtrum, low set and malformed ears, a short neck, hypoplastic nails on both index fingers, widened interdigital spaces between the toes, dilated lateral ventricles, right hydronephrosis, a dilated right ureter, mental and motor developmental delay, and generalised hypotonia. PMID- 1920372 TI - Pallister-Killian syndrome: additional manifestations of cleft palate and sacral appendage. AB - We report a case of Pallister-Killian syndrome in a 28 week gestation infant. In addition to the characteristic phenotype, this patient had a cleft palate, diaphragmatic hernia, sacral appendage, and imperforate anus. The lymphocyte karyotype showed 96% 46,XX/4% 47,XX+i (12p) and the fibroblast karyotype 47,XX,+marker (presumed i(12p]. Fibroblast cytogenetic studies should be considered in all cases of diaphragmatic hernia associated with other malformations. PMID- 1920373 TI - Facial dysmorphism: a marker of autosomal dominant cranial diabetes insipidus. AB - We report a family with autosomal dominant cranial diabetes insipidus in which a characteristic facial appearance of hypertelorism, broad and prominent nasal bridge, short nose, and long philtrum is seen in affected members. PMID- 1920374 TI - Neurosonography and pathology in the Schinzel-Giedion syndrome. AB - We describe a case of the Schinzel-Giedion syndrome, where increasing ventriculomegaly, intraventricular bands, and subependymal pseudocysts were shown by ultrasound of the head. Subsequent neuropathology confirmed the hydrocephalus. PMID- 1920375 TI - Cystic fibrosis screening and community genetics. PMID- 1920376 TI - False positive results with immunoreactive trypsinogen screening for cystic fibrosis owing to trisomy 13. PMID- 1920377 TI - Anesthetic management for instrumentation of the pregnant rhesus monkey. AB - The anesthetic procedures used and the responses observed during maternal instrumentation on 38 pregnant rhesus monkeys (Macaca mulatta) during the second half of gestation are reported. A laparotomy with maternal instrumentation was performed in all animals. Anesthesia was induced with ketamine and maintained with halothane. Two animals delivered within five days of anesthesia and surgery and were unable to undergo experimentation. The remaining 36 animals underwent successful experimentation. Dysrhythmias, hypotension, and hypothermia were identified as complications of anesthesia. PMID- 1920378 TI - The use of a urinary estrone conjugates assay for detection of optimal mating time in the cynomolgus macaque (Macaca fascicularis). AB - Forty-four female cynomolgus macaques (Macaca fascicularis) were examined to determine the optimum fertile period for mating. Daily urinary estrone conjugates (E1C) were measured, beginning on day 7 of the menstrual cycle, until a 1.5-gold E1C rise above the baseline was detected. The females were bred the next morning. Pregnancies were verified in all animals at day 18 postbreeding, and/or on day 25 postbreeding. Serum progesterone levels were used to correlate the relationship between ovulation and the E1C peak. Forty-four of the 57 cycles indicated a urinary E1C peak between days 10-15 of the menstrual cycle; this peak occurred on the day following the initial 1.5-fold to twofold rise in 90% of the cycles. A single 2-hr mating period the day before, the day of, or the day after the E1C peak resulted in conception in 17 of 44 (38.6%) animals. PMID- 1920379 TI - A baboon model for in vivo assessment of mucociliary lung clearance. AB - A suitable baboon model (Papio ursinus) for assessing inhibitory effects on mucociliary lung clearance was required. Clearance of various dimensions of nebulized particles (99mTc-labelled) was monitored with the animals (n = 6) under either ketamine or pentobarbitone anaesthesia. The best prospect of substantial and reproducible clearance in spite of the inhibition by the anaesthesia were obtained with pentobarbitone, and using nebulized radiolabelled particles of diameter range between 10 and 45 microns, thus avoiding trapping in the non ciliary alveoli. PMID- 1920380 TI - Disseminated histoplasmosis in a SIV-infected rhesus monkey. AB - Disseminated histoplasmosis due to Histoplasma capsulatum was diagnosed in a rhesus monkey inoculated with simian immunodeficiency virus (SIV). Immunohistochemical staining of tissues for viral core antigens revealed that those macrophages that expressed viral antigen contained few or no fungal organisms, while those that were filled with fungal organisms did not express viral antigen. This is a previously undocumented condition in a SIV-infected macaque, and suggests that SIV infection of individual macrophages is not the cause of macrophage dysfunction in SIV infections. PMID- 1920381 TI - Plasma-free amino acid concentrations during ketamine anesthesia in the rhesus monkey: a short methodological study. AB - The effect of ketamine anesthesia on the pattern of free amino acids in plasma was investigated in four healthy non-pregnant rhesus monkeys. Blood samples were collected at intervals during a period of 150 min both with and without anesthesia. Repeated measures analysis of variance, with time and ketamine/control as trial factors, was used. In only four amino acids were any changes with time or with ketamine treatment observed, the rest remaining unchanged. Ketamine anesthesia seemed to reduce the concentrations of several amino acids, but the findings were not conclusive. PMID- 1920383 TI - Siderophilic bodies associated with hemosiderosis and atypical mycobacterial infection in an island siamang (Hylobates syndactylus). AB - Laminated iron concretions were noted in the liver of an aged siamang (Hylobates syndactylus) that had granulomatous enteritis and hepatitis due to Mycobacterium avium intracellulare infection. Preexisting hepatic siderosis, iron sequestration in macrophages, and compromised macrophage function due to mycobacterial infection are proposed as the basis for the abundance and size of the concretions. Similar siderophilic bodies and concomitant siderosis occurred in other siamangs. The concretions are similar to Schumann bodies and Michaelis Gutmann bodies associated with granulomatous disease in other species. PMID- 1920382 TI - Prevalence of anti-Toxoplasma gondii antibodies in Cebus spp in the Santa Fe Zoological Park of Medellin, Colombia. AB - The prevalence of anti-Toxoplasma gondii antibodies was studied in 47 nonhuman primates of the Cebus species in the Santa Fe Zoological Park in Medellin, Colombia. Specific IgG titers (greater than 1/64) were detected in 40.9% of C. albifrons studied (n = 22), 13.3% of C. capucinus (n = 15), and 0% of C. apella (n = 10). Specific IgM was not detected in any of the animals studied. PMID- 1920384 TI - Isolation of functional polymorphonuclear leukocytes from rhesus monkeys using discontinuous Ficoll-Hypaque density gradients. AB - A simple, rapid method for separating polymorphonuclear leukocytes (PMNs) from adult rhesus monkey blood, based on the use of a discontinuous gradient of Ficoll Hypaque (densities, 1.100, 1.077) has been developed. Using this method, 71.1% of the PMNS were recovered in a layer with a purity of 91% PMNs with very few contaminating erythrocytes. The added advantage of the method described here is that a higher chemotactic activity was retained. PMID- 1920385 TI - Assembly and sealing of tight junctions: possible participation of G-proteins, phospholipase C, protein kinase C and calmodulin. AB - The making and sealing of a tight junction (TJ) requires cell-cell contacts and Ca2+, and can be gauged through the development of transepithelial electrical resistance (TER) and the accumulation of ZO-1 peptide at the cell borders. We observe that pertussis toxin increases TER, while AIF3 and carbamil choline (carbachol) inhibit it, and 5-guanylylimidodiphosphate (GTPTs) blocks the development of a cell border pattern of ZO-1, suggesting that G-proteins are involved. Phospholipase C (PLC) and protein kinase C (PKC) probably participate in these processes since (i) activation of PLC by thyrotropin-1 releasing hormone increases TER, and its inhibition by neomycin blocks the development of this resistance; (ii) 1,2-dioctanoylglycerol, an activator of PKC, stimulates TER development, while polymyxin B and 1-(5-isoquinoline sulfonyl)-2-methyl piperazine dihydrochloride (H7), which inhibit this enzyme, abolish TER. Addition of 3-isobutyl-1-methyl-xanthine, dB-cAMP or forskolin do not enhance the value of TER, but have just the opposite effect. Trifluoperazine and calmidazoline inhibit TER development, suggesting that calmodulin (CaM) also plays a role in junction formation. These results indicate that junction formation may be controlled by a network of reactions where G-proteins, phospholipase C, adenylate cyclase, protein kinase C and CaM are involved. PMID- 1920386 TI - Localization of sodium absorption and chloride secretion in an intestinal epithelium. AB - Hen coprodeum absorbs sodium electrogenically and, when stimulated by theophylline, secretes chloride. In this study the vibrating microprobe technique was used to localize the transport of these ions to intestinal villi/folds and crypts. With the isolated, stretched epithelium, controlled by light microscopy and scanning electron microscopy, in open circuit, currents were inward, 40 +/- 7 microA/cm2, 50 microns vertically above villi, and outward, 36 +/- 7 microA/cm2 above crypts. The currents decayed exponentially to near zero at 300 microns with the same length constant. A physical model simulating the observed loci of current sources and sinks predicts potential profiles consistent with our data. Extrapolation of the currents gives a surface potential of 45 microV, negative on villi and positive above crypts. Short circuiting increased villus current to 86 +/- 27 microA/cm2 at 50 microns, and amiloride treatment reduced it to -8 microA/cm2; in both cases crypt currents were abolished. The inward currents are compatible with sodium absorption. Induction of chloride secretion after amiloride treatment, resulted in current circuits similar to those induced by sodium absorption, with villus currents of 23 +/- 7 microA/cm2. This is in accord with chloride secretion at the villi. Quantitative estimates of crypt number (860/cm2) and opening diameter (15 microns), in conjunction with isotopic measurements of active and electrical potential-driven ion fluxes demonstrate, however, that only 4% of the potential-driven co-ion transport occurs through the crypts. This indicates that nearly all chloride secretion comes from the sodium absorbing villar area. Were the chloride secretion to occur solely from the crypts, the current should have been in the opposite direction and 10,000-fold larger. PMID- 1920387 TI - Effect of cholesterol and dipalmitoyl phosphatidylcholine enrichment on the kinetics of Na-Li exchange of human erythrocytes. AB - The effects of cholesterol loading and depletion and of a 10% replacement of native phosphatidylcholine by dipalmitoyl phosphatidylcholine (di 16:0-PC) on kinetic properties of human red cell Na-Li exchange have been studied. Compared to control erythrocytes (cholesterol/phospholipid ratio (C/P = 0.8-0.9], Vmax of phloretin-sensitive Li uptake and of Li efflux stimulated by extracellular Na (Nao) were reduced by 15-30% in cholesterol-loaded red cells (C/P = 1.05-1.33). The apparent Km values for external Li (Lio) and for internal Li (Lii) were decreased by about one-third in these cells. Cholesterol depletion (C/P = 0.7) exerted opposite effects on the kinetics of Nao-dependent Li efflux. On augmenting C/P from 0.66 to 1.0, Vmax of Nao-dependent Li efflux was reduced by about 30%; increasing C/P above 1.0 caused no further lowering of Vmax.Li leakage rates monotonically decreased over the whole range of C/P ratios examined (0.66 1.3). This indicates that Na-Li exchange and Li leak are differentially affected by cholesterol. Incorporation of di 16:0-PC (replacement of 3% of total red cell phospholipids) caused similar kinetic alterations of Na-Li exchange as a rise in membrane cholesterol by 20-50%. Notably, selective incorporation of di 16:0-PC into the outer monolayer increased both intra- and extracellular Li binding affinities of Na-Li exchange and lowered its maximum velocity. Thus, both di 16:0 PC enrichment and cholesterol loading exerted an uncompetitive type of transport inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920388 TI - A transient outward current dependent on external calcium in rat cerebellar granule cells. AB - The outward potassium current of rat cerebellar granule cells in culture was studied with the whole-cell patch-clamp method. Two voltage-dependent components were identified: a slow current, resembling the classical delayed rectifier current, and a fast component, similar to an IA-type current. The slow current was insensitive to 4-aminopyridine and independent of external Ca2+, but significantly inhibited by 3 mM tetraethylammonium. The fast current was depressed by external 4-aminopyridine, with an ED50 = 0.7 mM, and it was abolished by removal of divalent cations from the external medium. The sensitivity of the transient outward current to different divalent cations was investigated by equimolar substitution of Ca2+, Mn2+ and Mg2+. In 2.8 mM Mn2+, the transient potassium conductance was comparable to that in 2.8 mM Ca2+, while in 2.8 mM Mg2+ the transient component was drastically reduced, as in the absence of any divalent cations. However, when Ca2+ was present, Mg2+ up to 5 mM had no effect. The transient current increased with increasing concentrations of external Ca2+, [Ca2+]o, and the maximum conductance vs. [Ca2+]o curve could be approximated by a one-site model. In addition, the current recorded with 5.5 mM BAPTA in the intracellular solution was not different from that recorded in the absence of any Ca2+ buffer. These results suggest that divalent cations modulate the potassium channel interacting with a site on the external side of the cell membrane. PMID- 1920389 TI - Memory for spatial location in retarded and nonretarded persons. AB - Item memory and memory for spatial location were examined in college students, mildly retarded persons and moderately retarded persons. They performed under semantic or nonsemantic encoding instructions to remember pictures presented in a large book. Recall and relocation (unexpected) tests followed immediately after studying the pictures and, again, 24 h later. Mildly retarded persons were deficient in memory for items (effortful processing), but not in memory for location (automatic processing). Moderately retarded persons were deficient in both types of memory. Additionally, there were IQ-related differences in the long term memory of location information, as well as item information. Location memory, as opposed to item memory, was shown to be (1) sensitive to encoding instruction, (2) insensitive to differences in intelligence, and (3) more sensitive to long-term forgetfulness. PMID- 1920390 TI - Self-reinforcement in mildly mentally retarded adults: effects of motivational orientation and instructional demand. AB - The effects of external (environmental) and internal (cognitive) self-influences of self-regulatory behaviour were investigated in 60 mildly mentally retarded adults. External conditions were three demand conditions (stringent, variable, and lenient). The 'internal' variable was an individual differences one, motivational orientation: one-half of the subjects were relatively intrinsically motivated and the other half were relatively extrinsically motivated. Both external and internal self-influences affected performance on a motor/attention task. Subjects in the stringent-demand condition worked harder, set higher performance standards and arranged leaner schedules of self-reinforcement than did subjects in the lenient demand condition. Intrinsically motivated subjects worked harder, set higher performance standards, and arranged leaner schedules of self-reinforcement than did extrinsically motivated subjects over all demand conditions. Furthermore, intrinsically motivated subjects chose higher performance standards than had been demonstrated to them in the lenient-demand condition, and also arranged leaner schedules of self reinforcement over all demand conditions than had been demonstrated to them, compared to extrinsically motivated subjects. Internal self-system characteristics appear to interact reciprocally with external demand characteristics to reveal substantial individual differences in patterns of self-reward behaviour. PMID- 1920391 TI - Treatment of epilepsy in mentally retarded patients with a slow-release carbamazepine preparation. AB - Pharmacokinetic properties and efficacy of a conventional (C) carbamazepine (CBZ) preparation divided into three daily doses and a slow-release CBZ preparation (SR) divided into two daily doses were evaluated in a randomized, double-blind, cross-over study. The trial started with a 8-week baseline period followed by the two treatment periods each 10 weeks long. At the end of each period, a 24-h blood sample series for determination of serum CBZ and carbamazepine-10,11-epoxide (CBZE) was collected. The occurrence of seizures was monitored day and night during the whole study period by experienced nurses. The mean age of the 20 evaluable patients was 24.9 and the duration of epilepsy 19.2 and carbamazepine treatment 7.0 years. The bioavailability of CBZ from the two preparations was similar. The mean fluctuation of serum CBZ concentration (Cmax-Cmin/Css) was 16% smaller during SR. The mean serum CBZ concentration in the morning samples was significantly (P less than 0.001) higher during SR treatment. The mean total number of seizures was approximately four per week and did not differ between the two treatments, but during the last 2 weeks of the study period the occurrence of seizures was significantly smaller during SR (P = 0.02). PMID- 1920392 TI - The partial monosomy 10q syndrome: report on two patients and review of the developmental data. AB - Two patients, a boy and a girl, with growth delay, mental retardation and mild dysmorphism due to a de novo terminal 10q deletion are described. A recognizable facial appearance with a prominent nose and dysplastic ears was present. Specific attention is given to the developmental and behavioural data of the children. A review is made of the psychologic data of the 18 earlier reported surviving cases. PMID- 1920393 TI - A model for cryosectioning based on the morphology of vitrified ultrathin sections. AB - Electron microscopy of vitrified ultrathin sections allows cell ultrastructure to be studied in the hydrated state. Sectioning of the frozen material is, however, a limiting step, since the cutting forces cause severe mechanical deformation. In order to address this problem, we have investigated the surface of cryosections. It is shown that cryosections have two fundamentally different surfaces. One surface is rough, deformed by cutting-induced deformation lines which are orientated perpendicular to the cutting direction. The other surface, in comparison, is not affected by those deformation lines. Except for knife marks it is smooth. In order to explain the observations, the following model is proposed. The rough relief corresponds to the former block face. Its roughness originates from material that is squeezed out of the section plane when the section is compressed in the cutting direction and bent away from the specimen block. The smooth section surface is the surface in contact with the knife during the sectioning. This contact keeps the surface smooth while imprinting the knife marks. PMID- 1920394 TI - Application of high-resolution scanning electron microscopy to biological macromolecules. AB - The development of ultrahigh-resolution scanning electron microscopes (SEMs) has made the observation of biological macromolecules feasible, but adequate preparation methods have not yet been established. Although it has been possible to observe some molecules after they have been spread on a carbon substrate, this method has not proved suitable for other molecules which exhibit lower contrast, or are more susceptible to damage by the electron beam. In this study we have applied heavy-metal impregnation methods using phosphotungstic acid, uranyl acetate, or osmium tetroxide mordanted by tannic acid. In addition, contamination due to the electron beam was reduced by improving the vacuum in the specimen chamber, and by the use of a heated specimen stage. Using these measures, haemocyanin, ferritin, apoferritin, thyroglobulin and immunoglobulin M were successfully image. Ultrahigh-resolution SEM seems likely to become an important means for studying the morphology of biological macromolecules. PMID- 1920396 TI - Gap-junction quantification in biological tissues: freeze-fracture replicas versus thin sections. AB - The relative efficiency of freeze-fracture replicas versus thin sections for the visualization and quantification of gap junctions in biological tissues has been evaluated. Both methods may underestimate gap-junction number--thin sections for reasons of tissue resolution and freeze-fracture replicas due to the mechanics of the fracturing process. Freeze-fracture misses gap junctions in regions of plasma membrane which are highly contoured, such as the overlapping basal cell processes of Drosophila imaginal wing discs and the interdigitating lateral membrane plications of intercalated discs in cardiac tissue. If the missed gap junctions are relatively large, as they are in both of these examples, freeze-fracture significantly underestimates the total gap-junctional area. Thin sections may miss small gap junctions, but in tissues which contain a range of gap-junction sizes the lost junctions constitute a relatively small fraction of the total junctional area. In neoplastic imaginal wing discs, thin sections were as efficient as freeze-fracture replicas in identifying even the smallest gap junctions. Although freeze-fracture may be the better technique for the qualitative and quantitative documentation of small gap junctions in tissues with relatively flat to gently contoured plasma membranes and thin sections may be the superior method for gap-junction quantification in tissues containing a range of gap-junctional sizes and highly contoured cellular processes, the data suggest that a combination of the two approaches should be utilized whenever possible. PMID- 1920395 TI - Platinum/iridium/carbon: a high-resolution shadowing material for TEM, STM and SEM of biological macromolecular structures. AB - Thin Pt/Ir/C coating films (1.5 nm) show a fine granularity and provide a high structural resolution in the transmission electron microscope (TEM) when applied to freeze-dried biological macromolecules. They keep their structure when exposed to atmospheric conditions, without the need of an additional stabilizing carbon layer, in contrast to conventional high-resolution shadowing materials such as Ta/W and Pt/C. However, the correct ratio of the components has turned out to be crucial. When evaporating Pt/Ir/C from the source electrode in an electron-beam heated evaporator, the ratio of the three elements changes progressively, and, consequently, the properties of such films depend strongly on the mass that has been pre-evaporated. In this paper we present a quantitative analysis of the composition of Pt/Ir/C films by wavelength-dispersive X-ray analysis (WDX) undertaken in association with TEM experiments. We applied Pt/Ir/C shadowing to two regular biological test specimens, the phage T4 type III polyhead and the HPI layer of Deinococcus radiodurans. It turns out that Pt/Ir/C films containing at least 25% C are three-dimensionally stable on the freeze-dried macromolecular samples. By the dramatically improved resolution power of the latest scanning electron microscopes (SEM) and the invention of the scanning tunnelling microscope (STM), two new surface-sensitive tools for the investigation of biological macromolecular structures became available. The Pt/Ir/C coating has proved to be well suited for STM and SEM imaging of freeze-dried biological structures because of its good electrical conductivity and its direct three dimensional stability. We compare STM, SEM and TEM images of freeze-dried and Pt/Ir/C-coated polyheads. PMID- 1920397 TI - A quantitative analysis of transparency in the human sclera and cornea using Fourier methods. AB - Cellular microstructure observed by scanning transmission electron microscopy (STEM) was analysed using Fourier methods. Fourier components of the density fluctuations in the sclera and the cornea of the human eye were quantified. The results show that the Fourier components responsible for the opacity of the sclera have sizes of the order of the wavelength of visible light. In the sclera, approximately 54% of the spectral energy of the density fluctuation falls in the range of 200-1100 nm (scattering range). In the cornea, approximately 24% of the total spectral energy falls in this range. The predominant Fourier components of the density fluctuations in the opaque sclera are approximately 300 nm in wavelength, whereas those of the transparent cornea are approximately 80 nm in wavelength. This method will be useful in quantitative analysis of microstructural changes accompanying biological phenomena such as normal development of transparency in the human lens, and abnormal loss of transparency during cataract formation. PMID- 1920398 TI - Cell surfaces and fractal dimensions. AB - The perimeters of the surface membranes of some different cell types have been digitized from electron micrographs and the data analysed in order to discover whether the perimeter can be described by a fractal dimension, df. Micrographs obtained at various magnifications and subsequently enlarged by different amounts have been used. Values of df ranging from 1.02 to 1.34 were manifested over a scale length of about one order of magnitude. Values of df were independent of the magnification, and were the same for cells of the same type. Possible implications of these results are discussed. PMID- 1920400 TI - Estimation of superhelical density in vivo from analysis of the level of cruciforms existing in living cells. PMID- 1920399 TI - Torsionally tuned cruciform and Z-DNA probes for measuring unrestrained supercoiling at specific sites in DNA of living cells. AB - We describe the development and application of "torsionally tuned" Z-DNA and cruciform probes for analyzing the level of unrestrained supercoiling at specific sites in the DNA of living cells. This approach is applicable for the analysis of dynamic differences in supercoiled DNA in different parts of plasmid, bacterial, or eukaryotic chromosomes. Using a psoralen-based assay, we have shown that the Z DNA forming sequence (CG)6TA(CG)6, cloned into plasmid pUC8, exists as Z-DNA in 30 to 40% of plasmid molecules in wild-type Escherichia coli. This level suggested an in vivo superhelical density of sigma = -0.034 at the site of insertion in the plasmid. A higher level of Z-DNA found in cells deficient in topoisomerase I (topA10) suggested an in vivo superhelical density of sigma = 0.048. We have constructed a set of torsionally tuned inverted repeated DNA molecules which require different superhelical densities for cruciform formation. Using these inverted repeats and a crosslink assay for cruciforms, we present quantitative evidence for the existence of cruciforms in living E. coli cells. Cruciform formation was dependent on DNA supercoiling in vivo and on the location of the inverted repeat within a plasmid. In topA10 cells cruciforms were detected in less than 0.5% of plasmids when cloned into two different transcriptional units: the lacZ and CAT genes. However, when cloned outside a transcriptional unit, cruciforms were found at levels up to 50% in topA10 cells. More cruciforms were found upstream than downstream from divergent promoters in pBR322. From analysis of the fraction of different inverted repeats existing as cruciforms in vivo and the levels of supercoiling required for cruciform formation in vitro, we estimate in vivo superhelical densities of sigma = -0.034 and -0.041 for the EcoRI site of pUC8-based plasmids in wild-type and topA10 cells, respectively. PMID- 1920401 TI - RecA-mediated annealing of single-stranded DNA and its relation to the mechanism of homologous recombination. AB - We demonstrate that RecA protein can mediate annealing of complementary DNA strands in vitro by at least two different mechanisms. The first annealing mechanism predominates under conditions where RecA protein causes coaggregation of single-stranded DNA (ssDNA) molecules and where RecA-free ssDNA stretches are present on both reaction partners. Under these conditions annealing can take place between locally concentrated protein-free complementary sequences. Other DNA aggregating agents like histone H1 or ethanol stimulate annealing by the same mechanism. The second mechanism of RecA-mediated annealing of complementary DNA strands is best manifested when preformed saturated RecA-ssDNA complexes interact with protein-free ssDNA. In this case, annealing can occur between the ssDNA strand resident in the complex and the ssDNA strand that interacts with the preformed RecA-ssDNA complex. Here, the action of RecA protein reflects its specific recombination promoting mechanism. This mechanism enables DNA molecules resident in the presynaptic RecA-DNA complexes to be exposed for hydrogen bond formation with DNA molecules contacting the presynaptic RecA-DNA filament. PMID- 1920402 TI - Effects of base mismatches on the structure of the four-way DNA junction. AB - Heteroduplex formation between imperfectly homologous DNA sequences may result in the formation of a four-way junction at which non-Watson-Crick base mismatches are present at the point of strand exchange. This raises the question of the effect of such mismatches on the structure and stability of these potential recombination intermediates. We have constructed a series of four-way DNA junctions containing single-base mismatches, and have studied the structure of the junctions by means of gel electrophoresis and chemical modification. We observed a range of effects on the structure of the junction, ranging from almost total abolition of folding through to normal accommodation into the folded structure. In some cases we observed gel electrophoretic data consistent with a dynamic equilibrium between folded and unfolded conformations, and in general the folded form was favoured at higher concentrations of cation. The effects of single mismatches on the structure of the four-way junction may be summarized in terms of: (1) the nature of the mismatch, where we note a correlation between the thermal stability of a given mismatch and its ability to be accommodated into a folded junction; or (2) the sequence context, where the effect of a given mismatch on the structure of a junction depends on the neighbouring base-pairs. These factors are illustrated by a junction, containing a C.A mismatch, that adopted alternate isomeric conformations dependent upon pH; as the state of protonation of the mispair changed, the structure was altered along with the interaction with neighbouring base-pairs. Most base mismatches may be accommodated into the folded stacked X-conformation of the four-way junction, but many require elevated cation concentration to permit the folding process to proceed. Some mismatches were found to be extremely destabilizing. PMID- 1920403 TI - Genomic structure of Chlamydomonas caltractin. Evidence for intron insertion suggests a probable genealogy for the EF-hand superfamily of proteins. AB - A clone containing the gene locus for Chlamydomonas caltractin, a 20,000 Mr calcium-binding protein that is a member of the EF-hand superfamily of calcium modulated proteins, was isolated and the structural organization of the gene was determined. The intron-exon organization was resolved by direct comparison of the genomic sequence with a caltractin cDNA. The promoter region does not contain the typical TATA or CCAAT boxes, but the sequences at the splice junctions are similar to those of other eukaryotes. The positions of the six introns in the caltractin gene do not typically define unit structures, nor do they coincide with those in genes for other members of the EF-hand superfamily. An analysis of exon sequences at the splice junctions in the genes of this multigene family was undertaken; evidence was obtained that supports the hypothesis that introns arose at proto-splice sites. A probable evolutionary history for the EF-hand superfamily based on intron insertion is offered. PMID- 1920405 TI - Molecular characterization of cuticle and interstitial collagens from worms collected at deep sea hydrothermal vents. AB - Two different collagens were isolated and characterized from the body walls of the vestimentiferan tube worm Riftia pachyptila and the annelid Alvinella pompejana, both living around hydrothermal vents at a depth of 2600 m. The acid soluble cuticle collagens consisted of a long triple helix (2.4 microns for Alvinella, 1.5 microns for Riftia) terminating into a globular domain. Molecular masses of 2600 and 1700 kDa, respectively, were estimated from their dimensions. The two cuticle collagens were also quite different in amino acid composition, in agreement with their different supramolecular organizations within tissues. Interstitial collagens corresponding to cross-striated fibrils underneath the epidermal cells could be solubilized by digestion with pepsin and consisted of a single alpha-chain. They were similar in molecular mass (340 kDa) and length (280 nm) but differed in composition and banding patterns of segment-long-spacing fibrils. This implicates significant sequence differences also in comparison to fibril-forming vertebrate collagens, although all form typical quarter-staggered fibrils. The thermal stability of the worm collagens was, with one exception (interstitial collagen of Riftia), in the range of mammalian and bird collagens (37 to 46 degrees C), and thus distinctly above that of shallow sea water annelids. Yet, their 4-hydroxyproline contents were not directly correlated to this stability. About 20% of Riftia collagen alpha-chain sequence was elucidated by Edman degradation and showed typical Gly-X-Y repeats but only a limited homology (45 to 58% identity) to fibril-forming vertebrate collagens. A single triplet imperfection and the variable hydroxylation of proline in the X position were additional unique features. It suggests that this collagen represents an ancestral form of fibril-forming collagens not directly corresponding to an individual fibril-forming collagen type of vertebrates. PMID- 1920404 TI - Ribosomal RNA identity elements for ricin A-chain recognition and catalysis. AB - Ricin is a cytotoxic protein that inactivates ribosomes by hydrolyzing the N glycosidic bond between the base and the ribose at position A4324 in eukaryotic 28 S rRNA. The requirements for the recognition by ricin A-chain of this nucleotide and for the catalysis of cleavage were examined using a synthetic oligoribonucleotide that reproduces the sequence and the secondary structure of the RNA domain (a helical stem, a bulged nucleotide, and a 17-member single stranded loop). The wild-type RNA (35mer) and a number of mutants were transcribed in vitro from synthetic DNA templates with phage T7 RNA polymerase. With the wild-type oligoribonucleotide the ricin A-chain catalyzed reaction has a Km of 13.55 microM and a Kcat of 0.023 min-1. Recognition and catalysis by ricin A-chain has an absolute requirement for A at the position that corresponds to 4324. The helical stem is also essential; however, the number of base-pairs can be reduced from the seven found in 28 S rRNA to three without loss of identity. The nature of these base-pairs can affect catalysis. A change of the second set from one canonical (G.C) to another (U.A) reduces sensitivity to ricin A-chain; whereas, a change of the third pair (U.A----G.C) produces supersensitivity. The bulged nucleotide does not contribute to identification. Hydrolysis is affected by altering the nucleotides in the universal sequence surrounding A4324 or by changing the position in the loop of the tetranucleotide GA(ricin)GA: all of these mutants have a null phenotype. If ribosomes are treated first with alpha sarcin to cleave the phosphodiester bond at G4325 ricin can still catalyze depurination at A4324. This implies that cleavage by alpha-sarcin at the center of what has been presumed to be a 17 nucleotide single-stranded loop in 28 S rRNA produces ends that are constrained in some way. On the other hand, hydrolysis by alpha-sarcin of the corresponding position in the synthetic oligoribonucleotide prevents recognition by ricin A-chain. The results suggest that the loop has a complex structure, affected by ribosomal proteins, and this bears on the function in protein synthesis of the alpha-sarcin/ricin rRNA domain. PMID- 1920406 TI - Identification and functional analysis of the nuclear localization signals of ribosomal protein L25 from Saccharomyces cerevisiae. AB - The regions of the large subunit ribosomal protein L25 from Saccharomyces cerevisiae responsible for nuclear localization of the protein were identified by constructing fusion genes encoding various segments of L25 linked to the amino terminus of beta-galactosidase. Indirect immunofluorescence of yeast cells expressing the fusions demonstrated that amino acid residues 1 to 17 as well as 18 to 41 of L25 promote import of the reporter protein into the nucleus. Both nuclear localization signal (NLS) sequences appear to consist of two distinct functional parts: one showed relatively weak nuclear targeting activity, whereas the other considerably enhances this activity but does not promote nuclear import by itself. Microinjection of in vitro prepared intact and N-terminally truncated L25 into Xenopus laevis oocytes demonstrated that the region containing the two NLS sequences is indeed required for efficient nuclear localization of the ribosomal protein. This conclusion was confirmed by complementation experiments using a yeast strain that conditionally expresses wild-type L25. The latter experiments also indicated that amino acid residues 1 to 41 of L25 are required for full functional activity of yeast 60 S ribosomal subunits. Yeast cells expressing forms of L25 that lack this region are viable, but show impaired growth and a highly abnormal cell morphology. PMID- 1920407 TI - Functional specialization within the alpha-subunit of Escherichia coli RNA polymerase. AB - The RNA polymerase core enzyme of Escherichia coli has the subunit composition alpha 2 beta beta', and when combined with one of several alternative sigma subunits (initiation-specificity) produces holoenzyme capable of all the steps of transcription. Dimerization of the alpha-subunit and association with the beta subunit trigger assembly of the core enzyme. Analyses of a set of deletion derivatives of rpoA (which encodes alpha) have indicated that as many as 94 carboxy-terminal amino acids (but not 153) can be removed without preventing assembly of core-like complexes in vitro. Detailed analyses of these deletion mutants have now been performed in vivo. alpha-Polypeptides truncated from the carboxy terminus to amino acid residues 235, 256 or 296 are assembled not merely into core, but also into holoenzyme-like complexes in vivo, and at least in the first two cases both of the two alpha-subunits can be replaced by the truncated versions. Nevertheless, none can complement rpoAts alleles for growth at 42 degrees C. We conclude that the domain(s) of alpha essential for the assembly of RNA polymerase (at least the major holoenzyme species) are confined to the amino terminal 235 amino acids, while some other essential function(s) require residues close to the carboxy terminus. PMID- 1920408 TI - 2.9 A resolution structure of an anti-dinitrophenyl-spin-label monoclonal antibody Fab fragment with bound hapten. AB - The crystal structure of the Fab fragment of the murine monoclonal anti dinitrophenyl-spin-label antibody AN02 complexed with its hapten has been solved at 2.9 A resolution using a novel molecular replacement method. Prior to translation searches, a large number of the most likely rotation function solutions were subjected to a rigid body refinement against the linear correlation coefficient between intensities of observed and calculated structure factors. First, the overall orientation of the search model and then the orientations and positions of the four Fab domains (VH, VL, CH1 and CL) were refined. This procedure clearly identified the correct orientation of the search model. The refined search model was then subjected to translation searches which unambiguously determined the enantiomer and position in the unit cell of the crystal. The successful search model was refined 2.5 A crystal structure of the Fab fragment of HyHel-5 from which non-matching residues in the variable domains had been removed. HyHel-5 is a murine monoclonal antibody whose heavy and light chains are of the same subclass (gamma 1, kappa, respectively) as AN02. After molecular replacement the structure of the AN02 Fab has been refined using simulated annealing in combination with model building and conjugate gradient refinement to a current crystallographic R-factor of 19.5% for 12,129 unique reflections between 8.0 and 2.9 A. The root-mean-square (r.m.s.) deviation from ideal bond lengths is 0.014 A, and the r.m.s. deviation from ideal bond angles is 3.1 degrees. The electron density reveals the hapten sitting in a pocket formed by the loops of the complementarity determining region. The dinitrophenyl ring of the hapten is sandwiched between the indole rings of Trp96 of the heavy-chain and Trp91 of the light-chain. The positioning of the hapten and general features of the combining site are in good agreement with the results of earlier nuclear magnetic resonance experiments. PMID- 1920409 TI - Structural and kinetic studies of the Fab fragment of a monoclonal anti-spin label antibody by nuclear magnetic resonance. AB - Nuclear magnetic resonance has been used to study the structure of the anti-spin label antibody AN02 combining site and kinetic rates for the hapten-antibody reaction. The association reaction for the hapten dinitrophenyl-diglycine (DNP diGly) is diffusion-limited. The activation enthalpy for association, 5.1 kcal/mol, is close to the activation enthalpy for diffusion in water. Several reliable resonance assignments have been made with the aid of recently reported crystal structure. Structural data deduced from the nuclear magnetic resonance (n.m.r.) spectra compare favorably with the crystal structure in terms of the combining site amino acid composition, distances of tyrosine residues from the unpaired electron of the hapten, and residues in direct contact with the hapten. Evidence is presented that a single binding site region tyrosine residue can assume two distinct conformations on binding of DNP-diGly. The AN02 antibody is an autoantibody. Dimerization of the Fab fragments is blocked by the hapten DNP diGly. The n.m.r. spectra suggests that some of the amino acid residues involved in the binding of the DNP-hapten are also involved in the Fab dimerization. PMID- 1920410 TI - Solution structure of [d(GTATATAC)]2 via restrained molecular dynamics simulations with nuclear magnetic resonance constraints derived from relaxation matrix analysis of two-dimensional nuclear Overhauser effect experiments. AB - Two-dimensional nuclear Overhauser effect (2D NOE) spectra have been used as the experimental basis for determining the solution structure of the duplex [d(GTATATAC)]2 employing restrained molecular dynamics (rMD) simulations. The MARDIGRAS algorithm has been employed to construct a set of 233 interproton distance constraints via iterative complete relaxation matrix analysis utilizing the peak intensities from the 2D NOE spectra obtained for different mixing times and model structures. The upper and lower bounds for each of the constraints, defining size of a flat-well potential function term used in the rMD simulations, were conservatively chosen as the largest or smallest value calculated by MARDIGRAS. Three different starting models were utilized in several rMD calculations: energy-minimized A-DNA, B-DNA, and a structure containing wrinkled D-DNA in the interior. Considerable effort was made to define the appropriate force constants to be employed with the NOE terms in the AMBER force field, using as criteria the average constraints deviation, the constraints violation energy and the total energy. Of the 233 constraints, one was generated indirectly, but proved to be crucial in defining the structure: the cross-strand A5-H2 A5-H2 distance. As those two protons resonate isochronously for the self-complementary duplex, the distance cannot be determined directly. However, the general pattern of 2D NOE peak intensities, spin-lattice relaxation time (T1) values, and 31P nuclear magnetic resonance spectra lead to use of the A3-H2 A7-H2 distance for A5 H2 A5-H2 as well. Five rMD runs, with different random number seeds, were made for each of the three starting structures with the full distance constraint set. The average structure from all 15 runs and the five-structure averages from each starting structure were all quite similar. Two rMD runs for each starting structure were made with the A5-H2 A5-H2 constraint missing. The average of these six rMD runs revealed differences in structure, compared to that with the full set of constraints, primarily for the middle two base-pairs involving the missing cross-strand constraint but global deviations also were found. Conformational analysis of the resulting structures revealed that the inner four to six base pairs differed in structure from the termini. Furthermore, an alternating structure was suggested with features alternating for the A-T and T-A steps. PMID- 1920411 TI - Refined crystal structure of the complex of subtilisin BPN' and Streptomyces subtilisin inhibitor at 1.8 A resolution. AB - The crystal structure of subtilisin BPN' complexed with a proteinaceous inhibitor SSI (Streptomyces subtilisin inhibitor) was refined at 1.8 A resolution to an R factor of 0.177 with a root-mean-square deviation from ideal bond lengths of 0.014 A. The work finally established that the SSI-subtilisin complex is a Michaelis complex with a distance between the O gamma of active Ser221 and the carbonyl carbon of the scissile peptide bond being an intermediate value between a covalent bond and a van der Waals' contact, 2.7 A. This feature, as well as the geometry of the catalytic triad and the oxyanion hole, is coincident with that found in other highly refined crystal structures of the complex of subtilisin Novo, subtilisin Carlsberg, bovine trypsin or Streptomyces griseus protease B with their proteinaceous inhibitors. The enzyme-inhibitor beta-sheet interaction is composed of two separate parts: that between the P1-P3 residues of SSI and the 125-127 chain segment (the "S1-3 site") of subtilisin and that between the P4-P6 residues of SSI and th 102-104 chain segment (the "S4-6 site") of subtilisin. The latter beta-interaction is unique to subtilisin. In contrast, the beta-sheet interaction previously found in the complex of subtilisin Novo and chymotrypsin inhibitor 2 or in the complex of subtilisin Carlsberg and Eglin C is distinct from the present complex in that the two types of beta-interactions are not separate. As for the flexibility of the molecules comprising the present complex, the following observations were made by comparing the B-factors for free and complexed SSI and comparing those for free and complexed subtilisin BPN'. The rigidification of the component molecules upon complex formation occurs in a very localized region: in SSI, the "primary" and "secondary" contact regions and the flanking region; in subtilisin BPN', the S1-3 and S4-6 sites and the flanking region. PMID- 1920412 TI - Protein docking and complementarity. AB - Predicting the structures of protein-protein complexes is a difficult problem owing to the topographical and thermodynamic complexity of these structures. Past efforts in this area have focussed on fitting the interacting proteins together using rigid body searches, usually with the conformations of the proteins as they occur in crystal structure complexes. Here we present work which uses a rigid body docking method to generate the structures of three known protein complexes, using both the bound and unbound conformations of the interacting molecules. In all cases we can regenerate the geometry of the crystal complexes to high accuracy. We also are able to find geometries that do not resemble the crystal structure but nevertheless are surprisingly reasonable both mechanistically and by some simple physical criteria. In contrast to previous work in this area, we find that simple methods for evaluating the complementarity at the protein protein interface cannot distinguish between the configurations that resemble the crystal structure complex and those that do not. Methods that could not distinguish between such similar and dissimilar configurations include surface area burial, solvation free energy, packing and mechanism-based filtering. Evaluations of the total interaction energy and the electrostatic interaction energy of the complexes were somewhat better. Of the techniques that we tried, energy minimization distinguished most clearly between the "true" and "false" positives, though even here the energy differences were surprisingly small. We found the lowest total interaction energy from amongst all of the putative complexes generated by docking was always within 5 A root-mean-square of the crystallographic structure. There were, however, several putative complexes that were very dissimilar to the crystallographic structure but had energies that were close to that of the low energy structure. The magnitude of the error in energy calculations has not been established in macromolecular systems, and thus the reliability of the small differences in energy remains to be determined. The ability of this docking method to regenerate the crystallographic configurations of the interacting proteins using their unbound conformations suggests that it will be a useful tool in predicting the structures of unsolved complexes. PMID- 1920413 TI - Two-dimensional and epitaxial crystallization of a mutant form of yeast RNA polymerase II. AB - A mutant form of yeast RNA polymerase II that lacks the fourth and seventh largest subunits, referred to as pol II delta 4/7, crystallized on positively charged lipid layers. Both single-layered (two-dimensional) crystals and several multi-layered crystal forms were obtained. The two-dimensional crystals, preserved in negative stain, diffracted strongly to about 1/20 A-1 and more weakly to 1/13 A-1 resolution. A projection map computed from averaged Fourier transforms revealed four pol II delta 4/7 complexes per unit cell and further revealed a cleft on the surface of the complex similar to that previously observed in the structure of Escherichia coli RNA polymerase. One of the multi layered crystal forms, preserved in negative stain, diffracted strongly beyond 1/15 A-1 resolution. Coherent diffraction from the multi-layered crystal is indicative of protein-protein interactions between layers and ordering in the third dimension. PMID- 1920414 TI - Crystallization and preliminary X-ray data of bromoperoxidase from Streptomyces aureofaciens ATCC 10762. AB - Bromoperoxidase from Streptomyces aureofaciens ATCC 10762, a non-haem haloperoxidase, has been crystallized using the hanging drop method. Preliminary X-ray diffraction studies show that the crystals belong to the cubic space group P2(1)3 with a = 123.4 A. The asymmetric unit contains a dimer of Mr = 60,200. The crystals diffract to at least 2.3 A resolution and are suitable for crystallographic structure analysis. PMID- 1920415 TI - X-ray solution scattering of Sindbis virus. Changes in conformation induced at low pH. AB - Alphaviruses, like many enveloped animal viruses, enter the cell by fusing with the cell membrane. This fusion occurs only in coated vesicles at a low pH. By using X-ray solution scattering of highly purified virus particles we have gained direct evidence that a drop in pH does not alter the structure of the virus core but does cause a significant change in the structure of the virus envelope. Thus these experiments give direct evidence to support the hypothesis that a reduction in pH causes a conformational change in the virus E protein, which enables it to promote fusion with the cell envelope and trigger virus infection. PMID- 1920416 TI - Crystallographic analysis of the neurophysin-oxytocin complex. A preliminary report. AB - Single crystals of a bovine neurophysin II-oxytocin complex have been obtained using (NH4)2SO4 as the precipitating agent. The crystals diffract to at least 2.7 A resolution, belong to Laue group 4/mmm and exhibit systematic absences consistent with either space group P4(1)2(1)2 or P4(3)2(1)2. The cell dimensions are a = b = 69.07 A and c = 113.26 A. The crystals contain one neurophysin oxytocin dimer per asymmetric unit. Based on a Vm of 2.9 A3/Da, the solvent content is calculated to be 58%. Chromatographic analysis of the dissolved crystals suggests the presence of three oxytocin molecules per neurophysin dimer. PMID- 1920417 TI - Comparison of the solution nuclear magnetic resonance and X-ray crystal structures of human recombinant interleukin-1 beta. AB - The solution structure of interleukin-1 beta determined by nuclear magnetic resonance spectroscopy is compared to three independently solved X-ray structures at 2 A resolution. It is shown that the solution and X-ray structures are very similar, both locally and globally. The atomic root-mean-square (r.m.s.) difference between the solution and X-ray structures is approximately 0.9 A for backbone atoms, approximately 1.5 A for all atoms and approximately 1 A for all atoms of internal residues. The largest differences are confined to some of the loops and turns connecting beta-strands. The atomic r.m.s. distribution of the 32 calculated solution structures about their mean co-ordinate positions (approximately 0.4 A for backbone atoms, approximately 0.8 A for all atoms and approximately 0.5 A for all atoms of internal residues) is approximately the same as the atomic r.m.s. differences between the three X-ray structures, indicating that the positional errors in the atomic co-ordinates determined by the two methods are similar. PMID- 1920418 TI - Low-resolution structure of recombinant human granulocyte-macrophage colony stimulating factor. AB - A recombinant form of human granulocyte-macrophage colony stimulating factor (GM CSF) which contains no carbohydrate has been crystallized. Multiple isomorphous replacement analysis using five heavy-atom derivatives has yielded an image of the structure at 6 A resolution that showed two molecules per asymmetric unit and allowed determination of the non-crystallographic symmetry transformation. The 6 A resolution result shows that the core of GM-CSF consists of four helices. The angles at which the helices pack together distinguishes this structure from known antiparallel four-helix bundle proteins. Consideration of the amino acid sequence properties and previous structural characterizations of GM-CSF leads to an assignment of the probable protein segments that form the helices. PMID- 1920419 TI - New crystal form of cytosolic chicken aspartate aminotransferase suitable for high-resolution X-ray analysis. AB - Four new crystal forms of chicken cytosolic aspartate aminotransferase have been grown from polyethylene glycol solutions. Crystals of the unliganded enzyme and of enzyme liganded with maleate diffract to 1.8 A resolution. Both the free and maleate-liganded enzymes crystallize in space group P2(1)2(1)2(1), but display slightly different cell dimensions (a = 56.9 A, b = 126.9 A and c = 124.6 A versus a = 56.5 A, b = 126.1 A and c = 124.6 A). The influence of various divalent metal ions, dioxane and non-ionic detergent beta-octylglucoside on crystallization has been investigated. The best crystals of liganded enzyme were obtained in the presence of Mg2+ ions, and these crystals were used for data collection to 1.9 A resolution. PMID- 1920420 TI - In a staphylococcal nuclease mutant the side-chain of a lysine replacing valine 66 is fully buried in the hydrophobic core. AB - The crystal structure of the staphylococcal nuclease mutant V66K, in which valine 66 is replaced by lysine, has been solved at 1.97 A resolution. Unlike lysine residues in previously reported protein structures, this residue appears to bury its side-chain in the hydrophobic core without salt bridging, hydrogen bonding or other forms of electrostatic stabilization. Solution studies of the free energy of denaturation, delta GH2O, show marked pH dependence and clearly indicate that the lysine residue must be deprotonated in the folded state. V66K is highly unstable at neutral pH but only modestly less stable than the wild-type protein at high pH. The pH dependence of stability for V66K, in combination with similar measurements for the wild-type protein, allowed determination of the pKa values of the lysine in both the denatured and native forms. The epsilon-amine of this residue has a pKa value in the denatured state of 10.2, but in the native state it must be 6.4 or lower. The epsilon-amine is thus deprotonated in the folded molecule. These values enabled an estimation of the epsilon-amine's relative change in free energy of solvation between solvent and the protein interior at 5.1 kcal/mol or greater. This implies that the value of the dielectric constant of the protein interior must be less than 12.8. Lysine is usually found with the methylene groups of its side-chain partly buried but is nevertheless considered a hydrophilic surface residue. It would appear that the high pKa value of lysine, which gives it a positive charge at physiological pH, is the primary reason for its almost exclusive confinement to the surface proteins. When deprotonated, this amino acid type can be fully incorporated into the hydrophobic core. PMID- 1920421 TI - mRNA degradation by processive 3'-5' exoribonucleases in vitro and the implications for prokaryotic mRNA decay in vivo. AB - Two 3'-5' exoribonucleases, polynucleotide phosphorylase and ribonuclease II play a central role in the degradation of bacterial mRNA to ribonucleotides. Sequences with the potential to form stem-loop structures can stabilize upstream mRNA against 3'-5' exoribonucleolytic attack in vivo by blocking the processive activities of these enzymes. For many mRNA species stem-loop structures appear to provide a very efficient block to decay from the 3' end, such that the rate determining step for mRNA decay occurs elsewhere in the transcript. We have examined the stalling of 3'-5' exoribonucleases at stem-loop structures in vitro. Although stem-loop structures alone can impede the progress of both enzymes, the duration of stalling at these structures in vitro is insufficient to account for the increased half-lives that they confer on mRNA in vivo. These data suggest that an additional factor, such as a stem-loop binding protein, is required for stabilization of mRNA by stem-loop structures in vivo. The implications for the regulation of mRNA stability are discussed. PMID- 1920422 TI - Structure of immunoglobulin G by scanning tunnelling microscopy. AB - Scanning tunnelling microscopy (STM) has been used to examine the shape of individual immunoglobulin G (IgG) molecules deposited onto a graphite surface. IgG was chosen for this study as it has a well-characterized and distinctive three-dimensional structure. The micrographs clearly reveal the IgG molecule as trilobed, corresponding with the known structural organization of IgG. Comparison of these images with the structure of IgG determined by X-ray crystallography shows that the STM images are consistent with the crystal structure. This illustrates that STM is a valuable technique for examining protein structure, allowing rapid determination of the overall molecular shape that is consistent with more established techniques. PMID- 1920423 TI - Composite of A and F-type 5' terminal sequences defines a subfamily of mouse LINE 1 elements. AB - The 5' terminus of full-length L1 elements contains transcriptional control sequences. In mouse L1 (L1Md) elements, these sequences exist as an array of tandem direct repeats. Two types of repeat units, termed A-monomers and F monomers, have been reported. Both monomers are about 200 bp in length but share no significant sequence homology. Previous studies have identified L1Md elements containing either A or F-monomers but not both. Here we describe three "composite" L1Md elements that contain both types of monomer sequence. Two of these composite L1Md elements are highly homologous and share the same structural rearrangements, implying that they arose from a common ancestor that has the same composite 5' end. PMID- 1920424 TI - Crystals of intact elongation factor Tu from Thermus thermophilus diffracting to high resolution. AB - The intact elongation factor Tu from the extreme thermophile Thermus thermophilus has been crystallized as a complex with the GTP analogue guanosine-5'-(beta,gamma imido)triphosphate. The crystals are very stable in the X-ray beam and diffract to 1.9 A resolution. They exhibit space group C2, with a = 150.3(6) A, b = 99.6(3) A, c = 40.1(1) A, beta = 95.4(2) degrees, and contain one elongation factor Tu molecule per asymmetric unit. PMID- 1920425 TI - Preliminary X-ray diffraction analysis of a crystallizable mutant of malate dehydrogenase from the thermophile Thermus flavus. AB - Malate dehydrogenase from mutant strain F428 of the thermophilic bacterium Thermus flavus has now been crystallized from polyethylene glycol 8000 in a form suitable for diffraction studies. The protein crystallizes in the orthorhombic P2(1)2(1)2(1) space group with unit cell dimensions a = 71.8 A, b = 88.6 A, c = 119.0 A. The asymmetric unit consists of one homodimer of molecular mass 67,000 Da. The X-ray diffraction extends beyond 1.7 A and a full data set to 1.9 A has been collected. PMID- 1920426 TI - Suboptimal sequence alignment in molecular biology. Alignment with error analysis. AB - A molecular sequence alignment algorithm based on dynamic programming has been extended to allow the computation of all pairs of residues that can be part of optimal and suboptimal sequence alignments. The uncertainties inherent in sequence alignment can be displayed using a new form of dot plot. The method allows the qualitative assessment of whether or not two sequences are related, and can reveal what parts of the alignment are better determined than others. It also permits the computation of representative optimal and suboptimal alignments. The relation between alignment reliability and alignment parameters is discussed. Other applications are to cyclical permutations of sequences and the detection of self-similarity. An application to multiple sequence alignment is noted. PMID- 1920428 TI - Three-dimensional structure of the neuraminidase of influenza virus A/Tokyo/3/67 at 2.2 A resolution. AB - An atomic model of the tetrameric surface glycoprotein neuraminidase of influenza virus A/Tokyo/3/67 has been built and refined based on X-ray diffraction data at 2.2 A resolution. The crystallographic residual is 0.21 for data between 6 and 2.2 A resolution and the r.m.s. deviations from ideal geometry are 0.02 A for bond lengths and 3.9 degrees for bond angles. The model includes amino acid residues 83 to 469, four oligosaccharide structures N-linked at asparagine residues 86, 146, 200 and 234, a single putative Ca2+ ion site, and 85 water molecules. One of the oligosaccharides participates in a novel crystal contact. The folding pattern is a beta-sheet propeller as described earlier and details of the intramolecular interactions between the six beta-sheets are presented. Strain invariant residues are clustered around the propeller axis on the upper surface of the molecule where they line the wall of a cavity into which sialic has been observed to bind. Strain-variable residues implicated in binding to antibodies surround this site. PMID- 1920427 TI - Novel mutational spectrum induced by N-methyl-N'-nitro-N-nitrosoguanidine in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase gene in diploid human fibroblasts. AB - The kinds and locations of mutations in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene of 75 independent mutants, derived from N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated normal human fibroblasts, were characterized by direct sequencing of mRNA-polymerase chain reaction (mRNA-PCR)-amplified cDNA. Treatment of human cells with low (6 or 8 microM) or high (10 or 12 microM) doses of MNNG resulted in 35-fold or 150-fold average increases in mutation frequency, respectively. A high frequency of mutants lacking a complete exon was observed in both groups. Further characterization of half of these mutants by DNA-PCR amplification of intron-exon boundaries showed that they contained base substitutions. The kinds of base substitutions differed distinctly between these two groups. In the low dose group, a broad mutational spectrum was observed: ten out of the 31 base substitutions were A.T to G.C transitions, six contained G.C to A.T transitions, and the other 15 exhibited transversions. In contrast, the majority (84%) of base substitutions among the high dose group were G.C to A.T transitions; the others (16%) were transversions. All of the 32 G.C to A.T transitions were located on the non-transcribed strand, assuming that the causative premutational lesion was O6-methylguanine. These results indicate preferential repair of lesions located on the transcribed strand. In addition, G.C to A.T and A.T to G.C transitions preferentially occurred at positions with guanine and thymine at the adjacent 5' position, respectively. PMID- 1920429 TI - Refined atomic structures of N9 subtype influenza virus neuraminidase and escape mutants. AB - The crystal structure of the N9 subtype neuraminidase of influenza virus was refined by simulated annealing and conventional techniques to an R-factor of 0.172 for data in the resolution range 6.0 to 2.2 A. The r.m.s. deviation from ideal values of bond lengths is 0.014 A. The structure is similar to that of N2 subtype neuraminidase both in secondary structure elements and in their connections. The three-dimensional structures of several escape mutants of neuraminidase, selected with antineuraminidase monoclonal antibodies, are also reported. In every case, structural changes associated with the point mutation are confined to the mutation site or to residues that are spatially immediately adjacent to it. The failure of antisera to cross-react between N2 and N9 subtypes may be correlated with the absence of conserved, contiguous surface structures of area 700 A2 or more. PMID- 1920430 TI - Dynamic Monte Carlo simulations of a new lattice model of globular protein folding, structure and dynamics. AB - A long-standing problem of molecular biology is the prediction of globular protein tertiary structure from the primary sequence. In the context of a new, 24 nearest-neighbor lattice model of proteins that includes both alpha and beta carbon atoms, the requirements for folding to a unique four-member beta-barrel, four-helix bundles and a model alpha/beta-bundle have been explored. A number of distinct situations are examined, but the common requirements for the formation of a unique native conformation are tertiary interactions plus the presence of relatively small (but not irrelevant) intrinsic turn preferences that select out the native conformer from a manifold of compact states. When side-chains are explicitly included, there are many conformations having the same or a slightly greater number of side-chain contacts as in the native conformation, and it is the local intrinsic turn preferences that produce the conformational selectivity on collapse. The local preference for helix or beta-sheet secondary structure may be at odds with the secondary structure ultimately found in the native conformation. The requisite intrinsic turn populations are about 0.3% for beta proteins, 2% for mixed alpha/beta-proteins and 6% for helix bundles. In addition, an idealized model of an allosteric conformational transition has been examined. Folding occurs predominantly by a sequential on-site assembly mechanism with folding initiating either at a turn or from an isolated helix or beta-strand (where appropriate). For helical and beta-protein models, similar folding pathways were obtained in diamond lattice simulations, using an entirely different set of local Monte Carlo moves. This argues strongly that the results are universal; that is, they are independent of lattice, protein model or the particular realization of Monte Carlo dynamics. Overall, these simulations demonstrate that the folding of all known protein motifs can be achieved in the context of a single class of lattice models that includes realistic backbone structures and idealized side-chains. PMID- 1920431 TI - High-resolution solution structure of reduced French bean plastocyanin and comparison with the crystal structure of poplar plastocyanin. AB - The three-dimensional solution structure of reduced (CuI) plastocyanin from French bean leaves has been determined by distance geometry and restrained molecular dynamics methods using constraints obtained from 1H n.m.r. (nuclear magnetic resonance) spectroscopy. A total of 1244 experimental constraints were used, including 1120 distance constraints, 103 dihedral angle constraints and 21 hydrogen bond constraints. Stereospecific assignments were made for 26 methylene groups and the methyls of 11 valines. Additional constraints on copper co ordination were included in the restrained dynamics calculations. The structures are well defined with average atomic root-mean-square deviations from the mean of 0.45 A for all backbone heavy atoms and 1.08 A for side-chain heavy atoms. French bean plastocyanin adopts a beta-sandwich structure in solution that is similar to the X-ray structure of reduced poplar plastocyanin; the average atomic root-mean square difference between 16 n.m.r. structures and the X-ray structure is 0.76 A for all backbone heavy atoms. The conformations of the side-chains that constitute the hydrophobic core of French bean plastocyanin are very well defined. Of 47 conserved residues that populate a single chi 1 angle in solution, 43 have the same rotamer in the X-ray structure. Many surface side-chains adopt highly preferred conformations in solution, although the 3J alpha beta coupling constants often indicate some degree of conformational averaging. Some surface side-chains are disordered in both the solution and crystal structures of plastocyanin. There is a striking correlation between measures of side-chain disorder in solution and side-chain temperature factors in the X-ray structure. Side-chains that form a distinctive acidic surface region, believed to be important in binding other electron transfer proteins, appear to be disordered. Fifty backbone amide protons form hydrogen bonds to carbonyls in more than 60% of the n.m.r. structures; 45 of these amide protons exchange slowly with solvent deuterons. Ten hydrogen bonds are formed between side-chain and backbone atoms, eight of which are correlated with decreased proton exchange. Of the 60 hydrogen bonds formed in French bean plastocyanin, 56 occur in the X-ray structure of the poplar protein; two of the missing hydrogen bonds are absent as a result of mutations. It appears that molecular dynamics refinement of highly constrained n.m.r. structures allows accurate prediction of the pattern of hydrogen bonding. PMID- 1920432 TI - Secondary structure of coliphage Q beta RNA. Analysis by electron microscopy. AB - The secondary structure of genomic RNA from the coliphage Q beta has been examined by electron microscopy in the presence of varying concentrations of spermidine using the Kleinschmidt spreading technique. The size and position of structural features that cover 70% of the viral genome have been mapped. The structural features that are visualized by electron microscopy in Q beta RNA are large. They range in size from 170 to 1600 nucleotides. A loop containing approximately 450 nucleotides is located at the 5' end of the RNA. It includes the initiation region for the viral maturation protein. A large hairpin containing approximately 1600 nucleotides is located in the center of the molecule. It is multibranched and includes most of the viral coat gene, the readthrough region of the A1 gene, and approximately one third of the viral replicase gene. Within the central hairpin, the initiation region for the viral replicase gene pairs with a region within the distal third of the viral coat gene. This structure may participate in the regulation of translational initiation of the viral replicase gene. Two structural variants of the central hairpin were observed. One of them brings the internal S and M viral replicase binding regions into juxtaposition. These observations suggest that the central hairpin may also participate in the regulation of translation of the viral coat gene. The secondary structures that are observed in Q beta RNA differ significantly from structures that we described previously in the genomic RNA of coliphage MS2 but are similar to structures we observed by electron microscopy in the related group B coliphage SP. PMID- 1920433 TI - Crystal structure of human alpha-lactalbumin at 1.7 A resolution. AB - The three-dimensional X-ray structure of human alpha-lactalbumin, an important component of milk, has been determined at 1.7 A (0.17 nm) resolution by the method of molecular replacement, using the refined structure of baboon alpha lactalbumin as the model structure. The two proteins are known to have more than 90% amino acid sequence identity and crystallize in the same orthorhombic space group, P2(1)2(1)2. The crystallographic refinement of the structure using the simulated annealing method, resulted in a crystallographic R-factor of 0.209 for the 11,373 observed reflections (F greater than or equal to 2 sigma (F)) between 8 and 1.7 A resolution. The model comprises 983 protein atoms, 90 solvent atoms and a bound calcium ion. In the final model, the root-mean-square deviations from ideality are 0.013 A for covalent bond distances and 2.9 degrees for bond angles. Superposition of the human and baboon alpha-lactalbumin structures yields a root mean-square difference of 0.67 A for the 123 structurally equivalent C alpha atoms. The C terminus is flexible in the human alpha-lactalbumin molecule. The striking structural resemblance between alpha-lactalbumins and C-type lysozymes emphasizes the homologous evolutionary relationship between these two classes of proteins. PMID- 1920434 TI - Refined structure of the hirudin-thrombin complex. AB - The structure of a recombinant hirudin (variant 2, Lys47) human alpha-thrombin complex has been refined using restrained least-squares methods to a crystallographic R-factor of 0.173. The hirudin structure consists of an N terminal domain folded into a globular unit and a long 17-peptide C-terminal in an extended chain conformation. The N-terminal domain binds at the active-site of thrombin where Ile1' to Tyr3' penetrates to the catalytic triad. The alpha-amino group of Ile1' of hirudin makes a hydrogen bond with OG of Ser195 of thrombin, the side-chains of Ile1' and Tyr3' occupy the apolar site, Thr2' is at the entrance to, but does not enter, the S1 specificity site and Ile1' to Tyr3' form a parallel beta-strand with Ser214 to Gly219. The latter interaction is antiparallel in all other serine proteinase-protein inhibitor complexes. The extended C-terminal segment of hirudin, which is abundant in acidic residues, makes many electrostatic interactions with the fibrinogen binding exosite while the last five residues are in a 3(10) helical turn residing in a hydrophobic patch on the thrombin surface. The precision of the complementarity displayed by these two molecules produces numerous interactions, which although independently generally weak, together are responsible for the high degree of affinity and specificity. Although hirudin-thrombin and D-Phe-Pro-Arg-chloromethyl ketone thrombin differ in conformation in the autolysis loop (Lys145 to Gly150), this is most likely due to different crystal packing interactions and changes in circular dichroism between the two are probably due to the inherent flexibility of the loop. An RGD sequence, which is generally known to be involved in cell surface receptor interactions, occurs in thrombin and is associated with a long solvent channel filled with water molecules leading to the surface from the end of the S1 site. However, the RGD triplet does not appear to be able to interact in concert in a surface binding mode. PMID- 1920435 TI - Beta-breakers: an aperiodic secondary structure. AB - We have studied the architecture of parallel beta-sheets in proteins and focused on the residues that initiate and terminate the beta-strands. These beta-breaker residues are at the origin of the kink between the beta-strand and the turn that precedes or follows it. beta-Breakers can be located automatically using a consensus approach based on algorithmic secondary structure assignment, solvent accessibility and backbone dihedral angles. These beta-breakers are conformationally homogeneous with respect to side-chain solvent accessibility and backbone dihedral angle profile. A sequence-structure correlation is noted: a restricted subset of amino acids is observed at these positions. Analysis of homologous protein sequences shows that these residues are more highly conserved than other residues in the loop. We conclude that beta-breakers are the structural analogs of the N and C-terminal caps of alpha-helices. The identification of this aperiodic substructure suggests a strategy for improving secondary structure prediction and may guide site-directed mutagenesis experiments. PMID- 1920436 TI - Serpin tertiary structure transformation. AB - Previous crystallographic analyses have demonstrated that proteolytic cleavage of the serpins can result in a dramatic transformation of their tertiary structure. Some 16 residues on the amino terminal side of the cleavage site are inserted into a large beta-sheet to become a central strand, separating the two cleaved residues by about 70 A. We have determined, in outline, the nature of the conformational change responsible for this transformation. After cleavage, a fragment of the protein, consisting of an alpha-helix and three strands of beta sheet, moves away from the rest of the structure to make the space for the new strand. This movement involves a new type of structural change: sheet residues in the small fragment slide along grooves in an alpha-helix that belongs to the rest of the protein. The general conservation of residues in the regions between the small fragment and the rest of the protein imply that the same mechanism will be found in all serpins that undergo this tertiary structure transformation. PMID- 1920437 TI - Molecular structure of a complete turn of A-DNA. AB - We have determined the crystal structure of the dodecamer d(CCCCCGCGGGGG), showing for the first time a complete turn of A-DNA. It has average structural parameters similar to those determined in fibres. Nevertheless it shows a considerable local variation in structure which is in part associated with the presence of a bound spermine molecule. We conclude that the local DNA conformation does not only depend on the base sequence, but may be strongly modified upon interaction with other molecules. In particular, the CpG sequence, which is found in hypersensitive regions of the genome, appears to be able to easily change its conformation under external influences. PMID- 1920438 TI - Correlation of metal decoration and topochemistry on protein surfaces. AB - On the surface of protein molecules the formation of metal clusters during vacuum condensation is controlled by topochemical features of the substrate and by specific properties of the decorating material. The resulting metal distribution (decoration pattern) can be mapped by electron microscopy in conjunction with image processing. We have applied this technique to freeze-etched crystals of the lumazine synthase-riboflavin synthase complex and its derivative obtained by binding of the heteropolytungstate (NaP5W30O110)(NH4)14.31 H2O. The decoration pattern of the free protein and its heteropolytungstate derivative showed marked differences. The correlation of these data with the X-ray structure of the protein showed an increased affinity of both gold and silver to the location of heteropolytungstate. Decoration sites can, but do not need to, be close to the protein surface. Actually, two of the observed decoration sites are located on a layer of ice as thick as 20 A, which apparently transmits underlying topochemical features. Preferential affinity of a site to a given metal must be seen as a property that depends on specific interaction with the decorating material but also on the differential affinities in adjacent areas. PMID- 1920439 TI - Structural and thermodynamic analysis of the packing of two alpha-helices in bacteriophage T4 lysozyme. AB - Packing interactions in bacteriophage T4 lysozyme were explored by determining the structural and thermodynamic effects of substitutions for Ala98 and neighboring residues. Ala98 is buried in the core of T4 lysozyme in the interface between two alpha-helices. The Ala98 to Val (A98V) replacement is a temperature sensitive lesion that lowers the denaturation temperature of the protein by 15 degrees C (pH 3.0, delta delta G = -4.9 kcal/mol) and causes atoms within the two helices to move apart by up to 0.7 A. Additional structural shifts also occur throughout the C-terminal domain. In an attempt to compensate for the A98V replacement, substitutions were made for Val149 and Thr152, which make contact with residue 98. Site-directed mutagenesis was used to construct the multiple mutants A98V/T152S, A98V/V149C/T152S and the control mutants T152S, V149C and A98V/V149I/T152S. These proteins were crystallized, and their high-resolution X ray crystal structures were determined. None of the second-site substitutions completely alleviates the destabilization or the structural changes caused by A98V. The changes in stability caused by the different mutations are not additive, reflecting both direct interactions between the sites and structural differences among the mutants. As an example, when Thr152 in wild-type lysozyme is replaced with serine, the protein is destabilized by 2.6 kcal/mol. Except for a small movement of Val94 toward the cavity created by removal of the methyl group, the structure of the T152S mutant is very similar to wild-type T4 lysozyme. In contrast, the same Thr152 to Ser replacement in the A98V background causes almost no change in stability. Although the structure of A98V/T152S remains similar to A98V, the combination of T152S with A98V allows relaxation of some of the strain introduced by the Ala98 to Val replacement. These studies show that removal of methyl groups by mutation can be stabilizing (Val98----Ala), neutral (Thr152----Ser in A98V) or destabilizing (Val149----Cys, Thr152----Ser). Such diverse thermodynamic effects are not accounted for by changes in buried surface area or free energies of transfer of wild-type and mutant side-chains. In general, the changes in protein stability caused by a mutation depend not only on changes in the free energy of transfer associated with the substitution, but also on the structural context within which the mutation occurs and on the ability of the surrounding structure to relax in response to the substitution.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1920440 TI - Analysis of protein main-chain solvation as a function of secondary structure. AB - We have analysed the hydration of main-chain carbonyl and amide groups in 24 high resolution well-refined protein structures as a function of the secondary structure in which these polar groups occur. We find that main-chain atoms in beta-sheets are as hydrated as those in alpha-helices, with most interactions involving "free" amide and carbonyl groups that do not participate in secondary structure hydrogen bonds. The distributions of water molecules around these non bonded carbonyl groups reflect specific steric interactions due to the local secondary structure. Approximately 20% and 4%, respectively of bonded carbonyl and amide groups interact with solvent. These include interactions with carbonyl groups on the exposed faces of alpha-helices that have been correlated previously with bending of the helix. Water molecules interacting with alpha-helices occur mainly at the amino and carbonyl termini of the helices, in which case the solvent sites maintain the hydrogen bonding by bridging between residues i and i 3 or i-4 at the amino terminus and between i and i+3 or i+4 at the carbonyl terminus. We also see a number of solvent-mediated Ncap and Ccap interactions. The water molecules interacting with beta-sheets occur mainly at the edges, in which case they extend the sheet structure, or at the ends of strands, in which case they extend the beta-ladder. In summary, the solvent networks appear to extend the hydrogen-bonding structure of the secondary structures. In beta-turns, which usually occur at the surface of a protein, exposed amide and carbonyl groups are often hydrated, especially close to glycine residues. Occasionally water molecules form a bridge between residues i and i+3 in the turn and this may provide extra stabilization. PMID- 1920441 TI - Crystallographic analysis of acrosomal bundle from Limulus sperm. AB - The acrosomal process of Limulus sperm contains a bundle of filaments composed of actin and a 102 kDa protein in a 1:1 molar ratio. The structure of the bundle in true discharge was investigated by electron cryomicroscopy, X-ray scattering and crystallographic image analysis. A bundle can be characterized as a quasi-crystal with continuously varying views along the bundle axis. Each segment of the bundle is found to obey the symmetry of space group P1, with a = b = 147 A, c = 762 A, alpha = 90 degrees, beta = 90.6 degrees, gamma = 120 degrees. A unit cell contains a helical repeat of the filament with a selection rule following that of an actin filament. A 24 A projection map based on the h0l view was reconstructed after averaging 5300 unit cells from six electron images. Filaments in this projection are well separated and clearly display a 21 screw symmetry. This screw symmetry results from the helical parameters of the bundle filament and is found to be a non-crystallographic symmetry element present in the unit cell. Our structural analysis has led to the proposal that the assembly of a stable bundle with a defined maximum diameter can be controlled by the crystallographic packing of the twisted filaments. PMID- 1920442 TI - Postnatal development of the vomeronasal epithelium in the rat: an ultrastructural study. AB - Three basic types of cells are distinguished in the rat vomeronasal epithelium at birth: bipolar neurons, supporting cells, and basal cells. Neurons at this time include both immature and differentiated cells. By the end of the first postnatal week, all neurons show morphological signs of maturity in their cytoplasm, including abundant granular and smooth endoplasmic reticulum, neurotubules, dense lamellar bodies, apical centrioles, and tufts of microvilli. During the third week microvilli are more frequently encountered and appear to be longer and more branched. Supporting cells appear well-developed by the second day after birth. During the first ten days of life, supporting cells lose their centrioles and all of the complex associated with ciliary generation in the apical zone. Basal cells appear to be more numerous in newborns than in older animals. Protrusions projecting into the lumen are frequently observed in the epithelium of newborn animals, both on the dendrites of neurons and on supporting cells. After the third week, such protrusions are only observed in the transitional zone between the sensory and the non-sensory epithelia of the vomeronasal tubes. In this transitional zone, a fourth cell type showing apical protrusions with microvilli differentiates. Cytoplasm in this type resembles that of neighboring ciliated cells but has no cilia or centrioles. These transitional cells are considered to be cells in an intermediate state of differentiation, between that of the differentiated neurons and supporting cells of the sensory epithelium and that of the predominate ciliated cells of the non-sensory epithelium. The results suggest that by the end of the third week the vomeronasal epithelium is morphologically mature. PMID- 1920443 TI - Three-dimensional reconstruction and cross-sectional anatomy of the thigh musculature of the developing chick embryo (Gallus gallus). AB - The technique of graphical reconstruction by orthogonal projection of serial sections is used to generate three-dimensional models of embryonic chick thigh musculature at Hamburger-Hamilton ('51) stages 36 (day 10) and 39 (day 13). Unique and conserved anatomical landmarks are described, which can be used to specify position along the proximo-distal axis of the thigh from cross-sectional appearance. These landmarks provide an important reference for both current and future experimentation in which a precise developmental site must be systematically and repeatedly sampled. PMID- 1920444 TI - Programmed cell death in the wing of Orgyia leucostigma (Lepidoptera: Lymantriidae). AB - Programmed cell death is an integral and ubiquitous phenomenon of development that is responsible for the reduction of wing size in female moths of Orgyia leucostigma (Lymantriidae). Throughout larval and pupal life, cells of the wing epithelium proliferate and interact to form normal imaginal discs and pupal wings in both sexes. But at the onset of adult development, most cells in female O. leucostigma wings degenerate over a brief, 2-day period. Lysosomes and autophagic vacuoles appear in cells of the wing epithelium shortly after it retracts from the pupal cuticle. Hemocytes actively participate in removing the resulting cellular debris. By contrast, epithelial cells in wings of developing adult males of O. leucostigma do not undergo massive cell death. Wing epithelium of female pupae transferred to male pupal hosts behaves autonomously in this foreign environment. By pupation, cells of the female wing apparently are committed to self-destruct even in a male pupal environment. Normal interactions among epithelial cells within the plane of a wing monolayer as well as between the upper and lower monolayers of the wing are disrupted in female O. leucostigma by massive cell degeneration. Despite this disruption, the remaining cells of the wing contribute to the formation of a diminutive, but reasonably proportioned, adult wing with scales and veins. PMID- 1920445 TI - Structure and morphogenesis of the eggshell and micropylar apparatus in the olive fly, Dacus oleae (Diptera: Tephritidae). AB - The egg of the olive fly, Dacus oleae (Diptera, Tephritidae), is laid inside olives and the larva eventually destroys the fruit. The oocyte is surrounded by several distinct layers which are produced during choriogenesis. The chorion covering the main body of the egg outside of the vitelline membrane includes a "wax" layer, an innermost chorionic layer, an endochorion consisting of inner and outer layers separated by pillars and cavities similar to their counterparts in Drosophila melanogaster, as well as inner and outer exochorionic layers. The anterior pole is shaped like an inverted cup, which is chiefly hollow around its base and has very large openings communicating with the environment. Holes through the surface of the endochorion result from deposition of endochorionic substance around follicular cell microvilli. An opening at the apex of the cup provides an entrance for sperm entering the micropylar canal, which traverses the endochorion and continues into a "pocket" in a thickened vitelline protrusion. The micropylar canal is formed by deposition of endochorion and vitelline membrane around an elongated pair of follicular cell extensions. These extensions later degenerate and leave an empty canal about 5 microns in diameter and the narrower pocket about 1 micron in diameter. Respiration is thought to be facilitated by openings at the base of the anterior pole as well as by openings through the "plastron" around the main body of the shell. PMID- 1920446 TI - Ultrastructural study of the blood cells of the beluga whale, Delphinapterus leucas. AB - General cytological and ultrastructural features of cells found in the peripheral blood of three captive beluga whales (Delphinapterus leucas) are described. We noted all major peripheral cell types common to the circulation of mammalian species, including polymorphonuclear neutrophils, eosinophils, basophils, lymphocytes, and monocytes, as well as myelocytes, erythroblasts, and plasma cells. Platelets and two populations (normal and hypochromic) of red blood corpuscles were observed. PMID- 1920447 TI - An evolutionary model for maximum likelihood alignment of DNA sequences. AB - Most algorithms for the alignment of biological sequences are not derived from an evolutionary model. Consequently, these alignment algorithms lack a strong statistical basis. A maximum likelihood method for the alignment of two DNA sequences is presented. This method is based upon a statistical model of DNA sequence evolution for which we have obtained explicit transition probabilities. The evolutionary model can also be used as the basis of procedures that estimate the evolutionary parameters relevant to a pair of unaligned DNA sequences. A parameter-estimation approach which takes into account all possible alignments between two sequences is introduced; the danger of estimating evolutionary parameters from a single alignment is discussed. PMID- 1920448 TI - Counterselection of GATC sequences in enterobacteriophages by the components of the methyl-directed mismatch repair system. AB - Weak to severe deficit of GATC sequences in the DNA of enterobacteriophages appears to be correlated with their undermethylation during growth in dam+ (GATC ade-methylase) bacteria. This observation is corroborated by the sequence analysis showing no evidence for site-specific mutagenicity of 6meAde. The MutH protein of the methyl-directed mismatch repair system recognizes and cleaves the undermethylated GATC sequences in the course of mismatch repair. To enquire whether the MutH function of the methyl-directed mismatch repair system participates in counterselection of GATC sequences in enterobacteriophages, we have studied the yield of bacteriophage phi X174 containing either 0, 1, or 2 GATC sequences, in wild type, dam, and mut (H, L, S, U) Escherichia coli. Following transfection with unmethylated DNA containing two GATC sequences, a net decrease in the yield of infective particles was observed in all bacterial mutH+ dam- strains, whereas no detectable decrease was observed in bacteria infected by DNA without GATC sequence. This effect of the MutH function is maximum in wild type and mutL and mutS bacteria whereas the effect is not significant in mutU bacteria, suggesting an interaction of the helicase II with the MutH protein. However, in dam+ bacteria, the presence of GATC sequences leads to an increased yield of infective particles. The effect of GATC sequence and its Dam methylation system on phage yield in mutH- bacteria reveals that methylated GATC sequences are advantageous to the phage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920449 TI - Evolution and sequence analysis of a human Y-chromosomal DNA fragment. AB - A Y-chromosomal DNA fragment has been isolated from a human Y-Charon 21A recombinant library. Evolutionary analysis of 1F5 indicates that the size and sequence of this fragment have been conserved in higher primates. Deletion mapping and in situ hybridization analysis have localized 1F5 to the middle euchromatic portion of the long arm of the human Y chromosome at Yq11.2. Sequence analysis revealed the presence of an atypical Alu element and two regions rich in polypyrimidine-polypurine residues. PMID- 1920451 TI - Cloning and characterization of Daphnia mitochondrial DNA. AB - The mitochondrial genome of Daphnia pulex (Crustacea, Cladocera) was cloned as a single fragment into the plasmid vector pUC12. The genome size, estimated from restriction endonuclease fragment lengths, is 15,400 +/- 200 base pairs. The GC content, estimated from thermal denaturation studies, is 42%. The positions of 39 cleavage sites were mapped for 14 restriction enzymes. The distribution of these sites within the genome is random (P = 0.44). Heterologous hybridizations with Drosophila sylvestris mitochondrial DNA (mtDNA) probes indicate that gene orders within Daphnia and Drosophila mtDNAs are similar. PMID- 1920450 TI - Phylogenetic depth of Thermotoga maritima inferred from analysis of the fus gene: amino acid sequence of elongation factor G and organization of the Thermotoga str operon. AB - The gene (fus) coding for elongation factor G (EF-G) of the extremely thermophilic eubacterium Thermotoga maritima was identified and sequenced. The EF G coding sequence (2046 bp) was found to lie in an operon-like structure between the ribosomal protein S7 gene (rpsG) and the elongation factor Tu (EF-Tu) gene (tuf). The rpsG, fus, and tuf genes follow each other immediately in that order, which corresponds to the order of the homologous genes in the str operon of Escherichia coli. The derived amino acid sequence of the EF-G protein (682 residues) was aligned with the homologous sequences of other eubacteria, eukaryotes (hamster), and archaebacteria (Methanococcus vannielii). Unrooted phylogenetic dendrograms, obtained both from the amino acid and the nucleotide sequence alignments, using a variety of methods, lend further support to the notion that the (present) root of the (eu)bacterial tree lies between Thermotoga and the other bacterial lineages. PMID- 1920452 TI - Mitochondrial DNA sequence divergence in the Melanogaster and oriental species subgroups of Drosophila. AB - The nucleotide sequence of a segment of the mitochondrial DNA from three Drosophila species (D. erecta, D. eugracilis, and D. takahashii), belonging to different subgroups of the melanogaster group has been determined. The segment encompasses three complete tRNA genes (tRNAtrp, tRNAcys, and tRNAtyr) and portions of two protein-coding genes: the subunit 2 of the NADH dehydrogenase (ND2) and the subunit 1 of the cytochrome oxidase (COI). Comparisons also involve homologous sequences already known for four other Drosophila species of the melanogaster group. Length differences were confined in the intergenic region where a long stretch of AT repeats was observed in one of the species analyzed. The three tRNA genes exhibit very different evolutionary rates, the most slowly evolving one, tRNAtyr, is adjacent to the 5' end of COI; tRNAs in similar positions have been previously shown to evolve slowly because they are probably involved in transcript processing. Although the rate of synonymous substitutions was very similar between ND2 and COI genes there were strong discrepancies between them in terms of the number of nonsynonymous substitutions. Differences have also been found in G + C content of the genes, which are likely to be linked to different selective pressures. There is a reduction in G + C content in the region where selective constraints are reduced. This suggests the existence of different levels of constraints along the sequenced segment. An overall analysis of the types of substitutions showed a decrease in A + T content during the course of evolution of the species. PMID- 1920453 TI - Structure and evolution of 5S rRNA genes and pseudogenes in the genus Aspergillus. AB - We have cloned and determined the nucleotide sequence of 18 DNA fragments hybridizing to 5S rRNA from two Aspergillus species--A. wentii and A. awamori. Four of the analyzed sequences were pseudogenes. The gene sequences of these two species were very similar and differed from Aspergillus nidulans at both constant and microheterogeneous sites. PMID- 1920456 TI - Organization and implementation of emergency services in the treatment of major trauma. AB - Peak medical care for heavy trauma involves a multifaceted approach. Time is the overriding factor in the successful care of these patients, so that a short access time to emergency services is crucial. A well-trained ambulance crew must be involved and should have access to emergency physicians in selected cases. Respiratory and cardiac function must be optimized, shock must be alleviated, and the sites of trauma must be immobilized or otherwise controlled. Finally, the patient should be transported to a center with an emergency department that has the ability to function as a 24-h trauma center. PMID- 1920457 TI - Diagnosis and management of head trauma. AB - The strategy of head injury management should be to minimize avoidable mortality and morbidity by reducing secondary brain damage. Patients with severe injuries are a minority, and their main needs are maintenance of the airway and nutrition. Some patients with less severe injuries are at risk for developing intracranial hematoma, and these need CT scanning. Pharmacological interventions may improve the outlook for patients with diffuse injuries associated with brain swelling. PMID- 1920454 TI - Evolutionary relationships among the permease proteins of the bacterial phosphoenolpyruvate: sugar phosphotransferase system. Construction of phylogenetic trees and possible relatedness to proteins of eukaryotic mitochondria. AB - The amino acid sequences of 15 sugar permeases of the bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS) were divided into four homologous segments, and these segments were analyzed to give phylogenetic trees. The permease segments fell into four clusters: the lactose-cellobiose cluster, the fructose-mannitol cluster, the glucose-N-acetylglucosamine cluster, and the sucrose-beta-glucoside cluster. Sequences of the glucitol and mannose permeases (clusters 5 and 6, respectively) were too dissimilar to establish homology with the other permeases, but short regions of statistically significant sequence similarities were noted. The functional and structural relationships of these permease segments are discussed. Some of the homologous PTS permeases were found to exhibit sufficient sequence similarity to subunits 4 and 5 of the eukaryotic mitochondrial NADH dehydrogenase complex to suggest homology. Moreover, subunits 4 and 5 of this complex appeared to be homologous to each other, suggesting that these PTS and mitochondrial proteins comprise a superfamily. The integral membrane subunits of the evolutionarily divergent mannose PTS permease, the P and M subunits, exhibited limited sequence similarity to subunit 6 of the mitochondrial F1F0-ATPase and subunit 5b of cytochrome oxidase, respectively. These results suggest that PTS sugar permeases and mitochondrial proton-translocating proteins may be related, although the possibility of convergent evolution cannot be ruled out. PMID- 1920455 TI - Drosophila fat body protein P6 and alcohol dehydrogenase are derived from a common ancestral protein. AB - Drosophila melanogaster alcohol dehydrogenase is an example of convergent evolution: it is not related to the ADHs of other organisms, but to short-chain dehydrogenases, which until now have been found only in bacteria and in mammalian steroid hormone metabolism. We present evidence that the Drosophila ADH is phylogenetically more closely related to P6, another highly expressed protein from the fat body of Drosophila, than it is to the short-chain dehydrogenases. The polypeptide sequence of P6 was inferred from DNA sequence analysis. Both ADH and P6 polypeptides have retained a high structural similarity with respect to the Chou-Fasman prediction of secondary structure and hydropathy. P6 is also homologous to the 25-kd protein from the fat body of Sarcophaga peregrina, whose sequence we have reexamined. The evolution of the P6-ADH family of proteins is characterized by a dramatic increase in the methionine content of P6. Methionine accounts for 20% of P6 amino acids. This is in contrast with the absence of this amino acid in mature ADH. There is evidence that P6 and the 25-kd protein have undergone a parallel and independent enrichment in methionine. When corrected for this, the rate of amino acid replacement shows that the P6-25-kd lineage diverged from insect ADH shortly before the divergence of the ADH gene (Adh) from its 3' duplication (Adh-dup). PMID- 1920458 TI - Diagnosis and management of spinal cord trauma. AB - New information on MRI findings after acute spinal cord injury, changing concepts on the timing of surgical intervention, and a clearer understanding of the pathophysiology of this injury will enable clinicians to better treat spinal cord injuries and lay the groundwork for continuing investigations aimed at improving neurological recovery after spinal cord injury. PMID- 1920459 TI - Inhibition of lipid peroxidation in CNS trauma. AB - It is believed that the key mechanism of protection of the injured spinal cord by methylprednisolone (MP) is the inhibition of posttraumatic lipid peroxidation. Large, i.v. bolus doses are required to achieve this effect, but the biphasic dose-response curve limits the dose size to approximately 30 mg/kg. The mechanism for the reversed effect at higher concentrations is believed currently to be membrane disruption. Early treatment is required because injury mediated by lipid peroxidation is largely irreversible. Furthermore, the time course of the protective effects parallels the tissue pharmacokinetics, defining the need for repeated maintenance dosing by bolus or infusion. The optimum duration of treatment has not been ascertained, but it would appear to extend throughout the period during which biochemical conditions that promote peroxidation exist within the injured cord. PMID- 1920460 TI - Methylprednisolone treatment of acute spinal cord injury: an introduction. AB - Contusion injuries of cat spinal cords rapidly block action potential conduction across the impact site. Ion-selective microelectrode measurements revealed large and immediate extracellular ionic derangements, sufficient to block conduction. As extracellular potassium recovers, evoked potentials often return but are lost again when white matter blood flow fall. The delayed decline of evoked potentials and blood flow suggest secondary injury processes that may respond to pharmacological therapy. High dose methylprednisolone (15-30 mg/kg) dramatically improved blood flow, extracellular ionic shifts, blood flow, and evoked potentials in cat spinal cords. Methylprednisolone also decreased tissue ionic shifts and improved locomotory recovery. In concomitant experiments, we showed that naloxone also prevented posttraumatic declines in blood flow and improved locomotory recovery. Examination of the spinal cords at 6-12 weeks after injury, revealed that many recovered animals had only 10% of spinal cord axons remaining. Other studies revealed that many axons surviving injury are demyelinated, suggesting that drugs that protect oligodendroglial cells may also have beneficial effects. PMID- 1920461 TI - Treatment of acute spinal cord injury with methylprednisolone: results of a multicenter, randomized clinical trial. AB - Although some evidence of neurological improvement with naloxone exists in this trial, the improvement was never significantly better than that seen for placebo. Methylprednisolone (MP) was effective in reducing some of the permanent paralysis after acute spinal cord injury at the doses studied, but only when treatment began within 8 h after injury. There is currently no support for the administration of higher or lower doses of the drug and an apparent contraindication to initiating administration of MP at any dose more than 8 h after injury. PMID- 1920462 TI - The treatment of head trauma: implications for the future. AB - The basic aspects of care and organization are going to be most important in these patients: determining who is best suited to provide the care, determining the best treatment, and determining the best venues for treatment. With regard to newer treatments, it will be necessary not only to definitely establish the efficacy of treatment but also to convince the individuals supporting what will be large, expensive trials that this extra benefit is worth the effort and expense required. PMID- 1920464 TI - Gingival hyperplasia related to orthodontic upper removable appliances: a report of 3 cases. PMID- 1920463 TI - Diagnosis and management of major trauma. AB - A regional trauma system involving trained hospital teams as well as physician manned ambulances and helicopters has been established in Norway. Emphasis is on written guidelines and the continuous evaluation of the results. A grading system of injury severity is used. Despite major advances in the initial treatment of shock and major trauma, posttraumatic pulmonary insufficiency still represents a problem. Our results indicate a beneficial effect of the early prophylactic use of high-dose corticosteroids in major chest trauma. The use of three doses of methylprednisolone was not associated with any increased risk of infection. PMID- 1920465 TI - Chronic periodontitis and a chronic swelling of the right index finger. PMID- 1920467 TI - Follow-up of patients and partners experiencing penile prosthesis malfunction and corrective surgery. AB - An interview study is reported involving 14 men who had experienced at least one penile prosthesis malfunction and corrective surgery. Six partners were interviewed separately. The results indicated a broad range of coping patterns in terms of fears and disappointments, but an overall outcome of six cases very satisfactory, five satisfactory despite various worries or complaints, and three unsatisfactory. The discussion emphasizes coping, doctor-patient communication, and difficulties in predicting long-term outcome in these cases. PMID- 1920466 TI - Sexual, psychological, and marital impact of self-injection of papaverine and phentolamine: a long-term prospective study. AB - This prospective study assessed the long-term effects of self-injection of papaverine hydrochloride and phentolamine mesylate along several critical domains for 42 men and 26 partners. Over the course of one year, men were, on average, injecting themselves five times monthly, with 84% of these injections producing satisfactory erections. Treatment resulted in statistically significant improvements in quality of erection, sexual satisfaction, frequency of intercourse, and coital orgasm. The women also demonstrated significant improvement in sexual satisfaction, arousal, frequency of intercourse, and coital orgasm. Decreases in general psychiatric symptomatology were apparent for men but not for partners. The dropout rate was 57%. The common side effects of treatment were development of fibrotic nodules (26%), abnormal liver function values (30%), and bruising (19%). We conclude that self-injection should be considered among the accepted treatments for erectile dysfunction. It does appear to enhance the sexual lives of men and women when the treatment is efficacious and the couple is motivated to utilize it. PMID- 1920468 TI - Results of surgery for veno-occlusive disease. AB - Surgery directed at veno-occlusive dysfunction in impotency has evolved since 1981, following the recognition that vascular disorders are the major source of etiology of impotency. As the diagnostic tests for concomitant arterial disease have become more sophisticated, the results for pure veno-occlusive surgery have improved. Details of postoperative results in 60 of the author's patients are discussed along with other published results. The failure rate is 30-50%. Success includes those patients who can then obtain an erection with pharmacological agents who were unable to do so prior to surgery. A discussion of why the surgery fails is presented. PMID- 1920469 TI - Psychological treatment of erectile dysfunction in men without partners: outcome results and a new direction. AB - Studies concerning the psychological treatment of erectile dysfunction in men without partners are reviewed. A significant majority of single men experience improved erectile functioning following surrogate-assisted or men's group therapy. However, the expense and unresolved legal status of surrogate therapy and logistical problems in forming men's groups limit the availability of these treatments. "Personal Potential" is a new audio cassette adjunct for individual therapy. To approximate a men's group experience, "Personal Potential" includes discussions by former clients, didactic presentations, communication roleplays, and sexual and social homework assignments. Routine attention to communication problems in men without partners may also increase patient satisfaction with intracavernosal vasodilator self-infections, penile implants, or vacuum constriction devices. PMID- 1920470 TI - Couples therapy for erectile disorders: conceptual and clinical considerations. AB - The increasing emphasis on surgical, pharmacological, and mechanical solutions to erectile failure in the past decade has led to a relative neglect of the importance of couples dynamics in both the genesis and maintenance of erectile failure. Yet ignoring such issues compromises the success of sex therapy. Systemic approaches, family-of-origin issues, transferential projections, and cognitive-behavioral interventions may all have a place in treatment. These conceptual approaches are reviewed and four key relationship variables, namely, status and dominance, sexual attraction and sexual "chemistry," intimacy and trust, and sexual scripts, are highlighted as being of special importance in the evaluation and treatment of erectile problems. PMID- 1920471 TI - Vacuum devices for the impotent. AB - Vacuum constriction devices for the treatment of impotence achieve entrapment of blood in the penis following mechanically produced tumescence. Following application, blood flow is sustained, and the majority of users can achieve either an erection or an erection-like state that is satisfactory for intercourse. Properly motivated men can use these devices long-term without serious side effects. The devices are particularly effective in the management of partial impotence; they represent an attractive alternative to surgical procedures upon the penis, intracavernosal injection of vasoactive drugs, and sexual abstinence. PMID- 1920472 TI - External vacuum devices in the treatment of erectile dysfunction: a one-year study of sexual and psychosocial impact. AB - This prospective study assessed the sexual and psychosocial effects of 12 months' use of an external vacuum device in the treatment of erectile dysfunction. Results showed that the external vacuum device produced erections sufficient for intercourse in 87% of the men in our sample. The dropout rate was only 20% over the 12-month period. Use of the external vacuum device was associated with improvements in men's and their partners' sexual functioning. These improvements included erections of better quality, increased partner arousal, and increased frequency of orgasm and sexual satisfaction for men and women. The external vacuum device was also associated with decreases in general psychiatric symptomatology for men. Similar improvements in psychological functioning were not found for partners. Side effects and factors in patient and partner acceptance of the external vacuum device are discussed. PMID- 1920473 TI - Assisted erection follow-up with couples. AB - Erection obtained with a vacuum pump can be a solution for the impotent man. In this study it was proposed to and discussed with couples, eleven of whom chose it as treatment. The mean age of the men was 54 years and 8 months. The estimated etiology of their erectile disorder was: biogenic, 4, mixed, 7. A 25-item questionnaire was administered to each couple. Results show that the device was a good solution and improved the sex life of both partners. They manifested a fair degree of satisfaction with its use. The presence and the participation of the female partner should be considered in therapeutic recommendations for erectile disorders. PMID- 1920474 TI - Beryllium and lung cancer: adding another piece to the puzzle of epidemiologic evidence. PMID- 1920476 TI - Scientists find better ways to find better drugs. PMID- 1920475 TI - Biomarkers help advance chemoprevention research. PMID- 1920477 TI - Italians mount strong cancer research program. PMID- 1920478 TI - Kentucky scientists combine reading and cancer prevention for low-literate women. PMID- 1920479 TI - Pro and con tobacco forces face off over state legislation. PMID- 1920480 TI - Lung cancer incidence among patients with beryllium disease: a cohort mortality study. AB - We have conducted a cohort mortality study on 689 patients with beryllium disease who were included in a case registry. An earlier mortality study on 421 of these patients was limited to males and resulted in a determination of a nonsignificant twofold lung cancer excess based on only seven lung cancer deaths. We have extended this earlier study by including females and by adding 13 years of follow up. Comparison of the 689 beryllium disease patients with the U.S. population resulted in a lung cancer standardized mortality ratio (SMR) of 2.00 (95% confidence interval = 1.33-2.89) based on 28 observed lung cancer deaths. Adjustment for smoking did not change these results. All causes of mortality were also significantly elevated (SMR = 2.19), largely because of the very high rate of deaths due to pneumoconioses (primarily beryllium disease) (SMR = 34.23; 158 deaths). No other causes of death were significantly elevated. The excess of lung cancer was consistent for both sexes and did not appear to increase with duration of exposure to beryllium or with time elapsed since first exposure to this element. The case registry included those with acute beryllium disease, which resembles a chemical pneumonitis, and those with chronic beryllium disease, which resembles other pneumoconioses. The lung cancer excess was more pronounced among those with acute disease (SMR = 2.32) than among those with chronic disease (SMR = 1.57). PMID- 1920481 TI - Increased hyperthermic response with prostaglandin E1 in VX2 liver carcinoma in rabbits. AB - Most studies examining the potential of vasoactive drugs to selectively reduce the blood flow in a tumor and to enhance the thermal response to hyperthermia have used tumors growing in muscle tissues. We investigated the effect of prostaglandin E1 on a VX2 liver carcinoma in 95 female Japanese white rabbits. During continuous 20-minute intravenous infusions of prostaglandin E1 at doses of 1, 3, and 5 micrograms/kg per minute in rabbits with this liver tumor, the mean arterial blood pressure decreased to 81%, 74%, and 51% of initial levels, respectively. In the tumor, regional blood flow was 86%, 70%, and 56% of initial levels, respectively; in the adjacent liver tissue, it was 149%, 110%, and 86% of initial levels, respectively. The tumor and adjacent liver tissues were heated by a microwave generator, and the liver tissue was kept at 42.0 degrees C. The average temperature at the center of the tumor, which was 43.0 degrees C in the absence of prostaglandin E1, increased to 44.3 degrees C, 44.3 degrees C, and 44.2 degrees C when doses of 1, 3, and 5 micrograms/kg per minute were given, respectively. The therapeutic effect was determined on the basis of the tumor growth ratio (geometric tumor volume 7 days after treatment/volume at start of treatment). Hyperthermia alone resulted in a small reduction in the tumor growth ratio--from the control value of 11.82 to a value of 9.03. Hyperthermia combined with prostaglandin E1 led to an augmented reduction in tumor growth ratio (4.28, 4.70, and 4.79 during 1, 3, and 5 micrograms/kg per minute, respectively), compared with findings with hyperthermia alone. These results indicate that prostaglandin E1 reduces tumor blood flow, elevates tumor temperature during hyperthermia, and retards tumor growth after local heat treatment. For these reasons, prostaglandin E1 may be an effective adjuvant drug in clinical studies of hyperthermia in liver tumor. PMID- 1920482 TI - Significant improvement of the survival of seminoma cells in vitro by use of a rat Sertoli cell feeder layer and serum-free medium. AB - Seminoma cell lines, essential to the study of the biology of seminoma, do not exist. Tissue culture conditions for establishing such cell lines have to be developed. Under conventional culture conditions, seminoma cells usually die within the first 3 days after plating. The enhanced survival of rat gonocytes when cocultured with rat Sertoli cells in serum-free medium suggests that seminoma cells, the neoplastic counterparts of gonocytes, might benefit from the same conditions. Indeed, when cocultured with rat Sertoli cells in a serum-free medium, viable seminoma cells could be demonstrated on the 11th day of culture. This result is a significant improvement over the results with conventional methods. PMID- 1920483 TI - Prospective study of serum cholesterol levels and large-bowel cancer. AB - Based on previous reports, it is uncertain whether serum cholesterol levels are inversely related to colon cancer risk. In this study, serum cholesterol levels were measured in 7926 Japanese-American men who were followed for over 20 years. Two hundred thirty-one incident cases of colon cancer and 97 cases of rectal cancer were identified. An increase in serum cholesterol levels was associated with a decrease in risk for colon cancer (P value for trend = .01) but not for rectal cancer. This association appeared stronger as the site of cancer moved from the sigmoid colon to the cecum. The data were further analyzed by interval from examination to diagnosis. The inverse association was present for colon cancer cases diagnosed within 10 years of examination (P value for trend less than .01), especially for cecum-ascending colon cancer cases (P less than .01). A similar inverse pattern was found for cecum-ascending colon cancer cases diagnosed after 10 years, but the association was not statistically significant. The results suggest that the preclinical effects of undiagnosed colon cancer contributed to the inverse association, but these effects do not entirely explain why the relationship with hypocholesterolemia was stronger in men who were subsequently diagnosed with right-sided colon cancer. PMID- 1920484 TI - Phase I study on the sequential administration of recombinant human interferon gamma and recombinant human interleukin-2 in patients with metastatic solid tumors. PMID- 1920485 TI - Multidrug resistance in acute myeloid leukemia. PMID- 1920486 TI - Tumorigenicity and dissemination of human tumors in congenitally immune-deficient mice. PMID- 1920487 TI - Further evidence that pesticides or herbicides cause non-Hodgkin's lymphoma. PMID- 1920488 TI - Antiestrogen resistance: mechanisms by which breast cancer cells undermine the effectiveness of endocrine therapy. PMID- 1920489 TI - New regulations on animal research add costs, variables. PMID- 1920490 TI - Scientists develop new interest in cancer vaccine research. PMID- 1920491 TI - Commission urges stronger leadership against AIDS. PMID- 1920492 TI - Potential role of tamoxifen in prevention of breast cancer. AB - Despite advances in early detection and treatment of breast cancer, primary prevention has not been well explored, especially for women at increased risk of disease due to reproductive factors and family history. There are, however, suggestions that primary prevention of breast cancer may be a realistic objective. Randomized clinical trials of adjuvant therapy for early-stage breast cancer have demonstrated a 35% decrease in contralateral breast cancers among women receiving tamoxifen compared with controls, suggesting a potential role for tamoxifen in chemoprevention of breast cancer in women at increased risk of the disease. Adjuvant therapy studies also demonstrate that tamoxifen is well tolerated by most patients and suggest additional health benefits from alterations in plasma lipid levels and stabilization of bone mineral loss in women receiving tamoxifen. Aspects of tamoxifen pharmacology, laboratory research, and clinical experience which support its investigation as a chemopreventive agent for breast cancer are summarized, and potential toxic effects are discussed. PMID- 1920493 TI - Acquired tamoxifen resistance: correlation with reduced breast tumor levels of tamoxifen and isomerization of trans-4-hydroxytamoxifen. AB - Acquired tamoxifen resistance represents a major cause of treatment failure in breast cancer. We implanted estrogen receptor-positive MCF-7 human breast cancer cells in athymic nude BALB/c mice as a model to study in vivo acquired tamoxifen resistance. After 4-6 months of tumor growth suppression by trans-tamoxifen, tumor progression was observed despite continued tamoxifen administration. Acquired resistance was not due to loss of estrogen receptors, to alterations in serum or tumor estrogen levels, or to changes in tamoxifen or its major metabolites in serum. Tamoxifen-resistant tumors remained estrogen dependent in vivo. However, resistance was also associated with the ability of tamoxifen to stimulate tumor growth. Resistant tumors were characterized by markedly lower intracellular tamoxifen levels and by isomerization of the potent antiestrogenic metabolite trans-4-hydroxy-tamoxifen to the less potent cis isomer. Metabolic tolerance, as manifested by alterations in cellular concentrations of tamoxifen and its metabolites, may thus be one mechanism for acquired tamoxifen resistance in breast cancer. PMID- 1920494 TI - Her-2/neu and INT2 proto-oncogene amplification in malignant breast tumors in relation to reproductive factors and exposure to exogenous hormones. AB - In previous studies in southern Sweden, early use of oral contraceptives has been found to be accompanied by an increased risk of developing premenopausal breast cancer, and the tumors developing in these patients have shown a more aggressive behavior. In the present study, amplification of the proto-oncogenes Her-2/neu (also known as ERBB2) and INT2 was studied in primary tumor specimens from 72 premenopausal women and was related to starting age of oral contraceptive use and other reproductive risk factors. Amplification of Her-2/neu was more common among early oral contraceptive users (i.e., those starting at less than or equal to 20 years of age) than among nonusers or late users (odds ratio [OR], 5.3; 95% confidence interval [CI], 1.6-16.7), whereas INT2 amplification did not differ significantly among those groups (OR, 0.9; 95% CI, 0.1-5.0). The likelihood of INT2 amplification was greater among users of progestins and those with a history of abortions before the first full-term pregnancy (OR, 9.0; 95% CI, 1.3-51.7; and OR, 18.6; 95% CI, 2.2-165.8, respectively). No significant relationships were found between proto-oncogene amplification and the variables of parity, age at first full-term pregnancy, or late abortion. The increased ORs persisted after adjustment for age at diagnosis and other risk factors. The findings suggest that the higher rate of Her-2/neu amplification among early oral contraceptive users is an effect of the oral contraceptive use per se rather than of the relative youth of the users. Moreover, the relationship between progestin use and early abortion and amplification of the INT2 gene is biologically plausible. PMID- 1920495 TI - Alteration of endocrine parameters in premenopausal women with breast cancer during long-term adjuvant therapy with tamoxifen as the single agent. AB - Tamoxifen is used to treat selected patients at each stage of breast cancer. Although most clinical experience has been obtained with postmenopausal women, increasing numbers of premenopausal women will be treated with 5 or more years of adjuvant tamoxifen therapy following surgery. Indeed, the proposed use of tamoxifen to prevent breast cancer in high-risk women could result in its extended use during the childbearing years. We have monitored the changes in circulating hormone levels from the ovary and pituitary gland in premenopausal (41-47 years old) women with stage I or II breast cancer during adjuvant therapy with tamoxifen as the single agent for 4-72 months following a mastectomy. Each patient (total eight) continued to menstruate, and ovulation occurred. Circulating levels of luteinizing hormone and follicle-stimulating hormone (except in one woman) remained in the normal range (determined in 12 regularly menstruating women in a control group). The levels of estradiol, estrone, and progesterone were elevated onefold to threefold. Prolactin levels decreased by 30%-40%, but the levels of sex hormone binding-globulin were unaffected. These data demonstrate that premenopausal women taking tamoxifen are potentially at risk for pregnancy and must be counseled about barrier contraception. Furthermore, the impact of many years of ovarian stimulation by tamoxifen must be evaluated, especially in women with node-negative disease or in healthy women in whom tamoxifen is used to prevent breast cancer. PMID- 1920496 TI - Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. AB - Results from epidemiological studies have generally indicated an association of dietary saturated animal fats with human breast cancer risk. Some studies, however, have suggested a similar association for some polyunsaturated vegetable fats shown to promote both rodent mammary carcinogenesis and metastasis. This study was performed to evaluate the effects of corn oil on growth and metastasis of MDA-MB-435 human breast cancer cells, which have a propensity for metastasis. Corn oil is rich in the omega-6 fatty acid linoleic acid. Fifty-eight female athymic nude mice (NCr-nu/nu) were fed a high-fat diet (23% wt/wt corn oil; 12% linoleic acid) or a low-fat diet (5% wt/wt corn oil; 2.7% linoleic acid). Seven days after diets were started, tumor cells (1 x 10(6) were injected into a mammary fat pad. The time to appearance of solid tumors and the tumor size were recorded. After 15 weeks, the study was terminated, and autopsies were performed to determine the weight of the primary tumor and the extent of metastasis. The latent interval for tumor appearance in the animals fed the high-fat diet was shorter than that in the low-fat diet group, and the tumor growth rate in the high-fat diet group showed a small but statistically significant increase compared with the low-fat diet group. Primary tumors developed in 27 of the 29 mice on the high-fat diet and in 21 of the 29 on the low-fat diet. Of the mice with palpable primary tumors, 18 of 27 in the high-fat diet group and eight of 21 in the low-fat diet group had macroscopic lung metastases. The extent of metastasis in the high-fat diet group was independent of the primary tumor weight, but only those in the low-fat diet group with primary tumors weighing more than 2 g developed metastases. These results suggest that a high-fat diet rich in omega-6 polyunsaturated fatty acid can enhance metastasis of human breast cancer cells in this mouse model. The findings support the need for further study of the relationship between dietary polyunsaturated fats and breast cancer risk and for experiments to determine the effect on metastasis of only a 50% difference in fat intake--the dietary goal of the proposed clinical trials of low fat dietary intervention in breast cancer patients. PMID- 1920498 TI - Bladder cancer in workers exposed to aniline. PMID- 1920497 TI - Service in Vietnam and risk of testicular cancer. PMID- 1920499 TI - Investment in cancer research pays off for other diseases. PMID- 1920500 TI - Growth of human tumor cells in athymic mice. PMID- 1920501 TI - End stage renal disease in minorities. AB - It is projected that the proportion of black Americans, American Indians, Asian Americans, and Hispanic Americans entering the ESRD program will continue to increase. Despite the increase in the average age of the ESRD population, the minorities entering the ESRD program are much younger. The major risk factors of ESRD--hypertension, diabetes, and glomerulonephritis--are affecting these minorities at a higher rate and in varying combinations. High prevalence and severity of hypertension followed by diabetes mellitus are the major risk factors in blacks, especially black women. Heroin and HIV nephropathies, tied to the epidemic of illicit drug abuse, have a major impact on young black men. The high prevalence of diabetes and the epidemic of glomerulonephritis in certain tribes are the major risk factors in American Indians. Hypertension and diabetes are the risk factors for the rapidly increasing Asian American population, especially for the elderly segment of this population. Diabetes predominates as the risk factor for the rapidly growing Hispanic American population, a group that needs to be identified separately within the ESRD program. Diabetes and hypertension are treatable, and adequate control can prevent progression of renal failure. However, with minority groups, it is difficult to fully implement the measures necessary to achieve this control. Outreach programs are necessary not only to provide medical treatment but to include instruction in socioeconomic and educational strategies. Programs that will seek out these patients and treat them should also educate them about their diet, about the detrimental effects of alcohol and smoking, and about the danger of substance abuse. Ultimately, these programs may be much cheaper than supporting a rapidly increasing ESRD program. PMID- 1920502 TI - Chronic mental illness and homelessness in black populations: prologue and prospects. AB - Psychiatry has shown little regard for the special health concerns of African Americans, who are disproportionately represented among America's homeless. Although psychiatric literature is replete with data on homeless mentally disordered citizens, only incidental references are made to African Americans to satisfy federally funded research guidelines mandating the inclusion of racial minorities. Additionally, psychiatry has hesitated to suggest corrective actions for this national scourge and has begun to raise questions about the efficacy of case management and demonstration projects. PMID- 1920503 TI - The relationship between neuropsychological measures and self-care skills in patients with cerebrovascular lesions. AB - The present investigation examined the relationship between performance on the Michigan Neuropsychological Battery (MNB) and selected self-care skills in a group of patients with unilateral cerebrovascular lesions. Among MNB measures, left-sided somatosensory and motor functions were the best predictors of self care skills, showing that in these stroke patients lower level cerebral functions mediated by the right hemisphere are more strongly related to the self-care skills examined than higher cerebral functions. Also, evidence that patients with cerebrovascular lesions in the left hemisphere performed better than patients with right hemisphere lesions in several self-care categories is further indication that right hemisphere processes have a special role to play in the mediation of these self-care activities. The research and clinical implications of these findings are noted. PMID- 1920504 TI - L-alpha-phosphatidylcholine-induced stimulation of PGI2 production in canine gallbladders following hypovolemic shock and Escherichia coli sepsis. AB - In vitro production of PGI2 in canine gallbladders subjected to hypovolemic shock and Escherichia coli sepsis was studied to determine whether a precursor above arachidonic acid in the cyclooxyenase cascade might be operative in the production of prostacyclin, which, in turn, may play a role in the pathogenesis of acute acalculous cholecystitis (AC). L-alpha-phosphatidylcholine (LaP), an arachidonic acid precursor, was used as the test agent. LaP did not stimulate PGI2 production from either gallbladder surface in the hypovelimic animals or the mucosa of the septic shock group. However, it did stimulate PGI2 production from the SS serosa compared with controls, 1375 +/- 432 versus 633 +/- 198 pg/cm2/min (P less than .05). In conclusion, lack of stimulation of PGI2 in the hypovolemic model suggests that PGI2 does not play a role in AC. Alternatively, it may play a role in preventing this disease process in septic shock. This study demonstrates the use of precursors of arachidonic acid and the cyclooxygenase pathway as active participants in the production of PGI2, although it is unclear whether the prostacyclin produced helps prevent AC in septic shock. PMID- 1920506 TI - Tonsillar abscess. AB - This article presents seven cases of patients with tonsillar abscess formation and discusses the pathophysiology of intratonsillar abscess formation. PMID- 1920505 TI - Pitted red cell counts in Nigerian children with sickle cell anemia: correlation with age and splenic size. AB - Using direct interference phase-contrast microscopy (Normansky Optics), pit counts were performed on 32 HbSS patients, aged 3 to 17 years. The influence of age and splenic size on counts were also investigated. Nine HbSS and 15 HbAA age and sex-matched, healthy individuals served as controls. The mean +/- SD counts in the three groups were 11.1 +/- 9.1%, 1.7 +/- 1.4% and 1.8 +/- 1.7%, respectively. The older SS patients tended to have higher values, but the linear correlation with age was not impressive (r = 0.28). Seventeen (53.1%) patients had counts greater than 10%, while 8 (25%) had less than 3.5%. Five patients with gross splenomegaly had a mean count of 4.3 +/- 1.9%, significantly lower than the figure of 12.3 +/- 7.9% for the patients without splenomegaly (P less than .001), demonstrating retained reticulo-endothelial function in such patients. PMID- 1920507 TI - A contrast: geriatric depression versus depression in younger age groups. AB - A major depressive illness can occur at any stage of the life cycle. This article discusses the various presentations of depressive illness in older persons and contrasts these disorders with other age groups. A mnemonic based on the word "depression" provides a summary of several causes of depressive illness. The discussion concludes with a few comments on the diagnosis and screening for depression. PMID- 1920508 TI - Primary malignant skin tumors in Nigerians. AB - Skin cancers, although uncommon, do occur in black Africans. Available literature on this subject from black African populations is scant, suggesting diminished interest. Eighteen cases of malignant skin tumors seen at the University of Port Harcourt Teaching Hospital over 3 years (1984 to 1987) were analyzed for diagnoses, site of tumors, sex, and age. Seven patients (39%) had malignant melanomas affecting only the soles of the feet, while the same number had squamous cell carcinomas widely distributed in various parts of the body. Basal cell carcinomas were found in four (22%) patients with face lesions. Only three albinos were in the series, and all three had squamous cell carcinomas. Melanin protection against sun-induced skin cancers gives a false sense of well-being. The need for renewed interest of the subject is emphasized. PMID- 1920509 TI - Magnetic resonance imaging of chest wall lesions. AB - Magnetic resonance imaging (MRI) demonstrates surface anatomy, nerves, and soft tissue pathology. Selective placement of the cursor lines in MRI displays specific anatomy. The MR images can then be used as adjunct in teaching surface anatomy to medical students and to other health professionals. Because the normal surface anatomy could be imaged at UCLA's radiology department, it was decided to image soft tissue abnormalities with MR to assist in patient care. Patients imaged were scheduled for special procedures of the chest or staging lymphangiograms. Patients were placed into categories depending on known diagnosis or interesting clinical presentation. The diagnostic categories included Hodgkin's disease, melanoma, carcinomas (eg, lung or breast), lymphedema, sarcomas, dermatological disorders, and neurological disorders. All images were orchestrated by the radiologist. This article discusses both the teaching and clinical impact on patient care. PMID- 1920510 TI - Diabetes in infancy: diagnosis and current management. AB - This article reviews diagnosis and management of infants with diabetes. These infants present with signs and symptoms confused with other more common illnesses in this age group. A physician examining an ill-appearing dehydrated infant, without any obvious cause for the dehydration, should quickly screen the urine for glucose and ketones. Diagnosis of diabetes is a problem when an infant has only hyperglycemia or ketonuria. Febrile illnesses, convulsions, and dehydration can cause these laboratory abnormalities. Once the diagnosis of diabetes is made in the infant, management is complicated by the difficulty in administering small doses of insulin, monitoring blood glucose, complementing insulin administration with feedings, and hypoglycemia. The potential for brain damage with unrecognized episodes of hypoglycemia is always a concern in infants. This article offers suggestions for treating hypoglycemia as well as guidelines for making insulin adjustments when the infant is ill. The physician should be aware of the psychosocial issues involving the family of an infant with diabetes. Optimism and ongoing support should be provided to the family, so that the infant can grow up healthy and possibly benefit from research on the cure of diabetes. PMID- 1920511 TI - Lisfranc fracture-dislocations: report of two cases. AB - Lisfranc fracture-dislocation is a rare but sometimes dramatic injury, most commonly associated with motor vehicle and industrial accidents, and falls from heights. Radiographic examination is a crucial point in the work-up of these patients. The most common findings on plain radiographs are separation of the bases of the first and second metatarsals and the "fleck" sign, a bony fragment resulting from a fracture of the base of the first or second metatarsal. These fractures are demonstrated in the two cases presented. We conclude that these lesions can usually be diagnosed with plain radiographs if scrupulous attention is paid when evaluating the normal anatomic alignments. Computed tomography should be reserved for equivocal cases. PMID- 1920512 TI - Challenge for the minority physician: gaining quality health care for the underserved. PMID- 1920513 TI - Racial differences in physicians and patients in relationship to quality of care. PMID- 1920514 TI - Cancer prognosis in black Americans: a mini-review. AB - There is significant disparity of cancer outcome (incidence, survival, and mortality) for black Americans when compared with white Americans. The extent of disease is inversely associated with survival and directly associated with mortality rates. Blacks, who tend to be diagnosed at later stages of cancer than their white counterparts, may have a poorer outcome even when diagnosed within the same stage. Socioeconomic status and class have been shown to be significant predictors of poor outcome, and blacks are disproportionately represented among the poor and disadvantaged. Some studies continue to show significant "race" effects after controlling for income, a result likely due to unmeasured related variables. Possible solutions are discussed that deal primarily with promotion of cultural and class- sensitive educational interventions and efforts aimed at overcoming barriers to early and effective prevention and treatment. A more comprehensive plan based on providing opportunities for upward mobility is likely to be the ultimate solution, but this will require national governmental commitment, which is not presently evident. PMID- 1920515 TI - AIDS-related behavioral research and nursing. AB - As efforts targeted at producing an effective vaccine or a definitive cure are still in early stages of development, health education and prevention continue to be this country's major line of defense against acquired immunodeficiency syndrome (AIDS). This defense is dependent on knowledge of behaviors that place individuals at risk of human immunodeficiency virus (HIV) exposure and disease progression. This article reviews the critical points in our state of knowledge and offers additional areas of need. Research is needed to determine a database of persons who use psychoactive substances and to understand the HIV-associated behaviors linked to drug use. Epidemiologic studies are necessary to appreciate the sexual, contraceptive, and childbearing practices of users of any psychoactive substance. Greater emphasis also is needed to investigate the inherent effects of various psychoactive substances on the immune, neurologic, and endocrine systems. While biomedical research continues, it is apparent that research from behavioral studies are crucial to education and prevention efforts. Nurse investigators are well-positioned to play an important role in accumulating this information. Given the critical role of drug abuse in the HIV epidemic, the public health significance cannot be overestimated. PMID- 1920516 TI - The relationship of immunity and nutrition to the acquisition of methicillin resistant Staphylococcus aureus. AB - Selected nutritional and immunological indices of 118 patients with methicillin resistant Staphylococcus aureus (MRSA) were reviewed retrospectively. Those patients with nosocomial infections had significantly (P less than .05) lower levels of serum albumin, total protein, absolute lymphocyte, and percentage of lymphocytes (on differential) than all others (ie, community-acquired infections and colonizations and nosocomial colonizations). Therefore, these parameters might be important indicators of subsequent MRSA infestation in certain patient populations. PMID- 1920518 TI - The radiological evaluation of the child with a myelomeningocele. AB - Seven hundred fifty-five children with myelomeningoceles were evaluated radiologically at the Children's Memorial Hospital in Chicago. From our material, we propose a diagnostic radiologic model to accurately evaluate the neurological problems in the myelomeningocele child. This model is based on the clinical symptoms in these children and the radiologic modalities of magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, myelography, and plain radiographs. We found MRI to be the best modality to evaluate the posterior fossa and total spine. Computed tomography and ultrasound are used to evaluate ventricular size. At times MRI may not adequately diagnose subtle cases of tethering of the spinal cord, cord infarction, arachnoid cysts, or diastematomyelia. In these cases, further evaluation may be necessary with real time ultrasound to look at cord pulsations and water soluble myelography with follow through CT to differentiate cord infarction, arachnoid cyst, localized hydromyelia, or diastematomyelia. If MRI is not adequate to completely visualize the cord because of the severe nature of the scoliosis, then water soluble myelography with CT is indicated. PMID- 1920517 TI - The relationship of blood pressure to a brief measure of anger during routine health screening. AB - A brief questionnaire (12 items) was developed to assess aspects of anger that could be expeditiously obtained during health screenings where medical students and residents can acquire valuable research and clinical experience simultaneously. Blood pressures were measured immediately upon sitting and after 3 minutes in 179 subjects who attended a health fair in Nashville. The questionnaire was administered after both blood pressure measurements were acquired. Scores on the measure of anger correlated significantly (P = .0009) with resting systolic blood pressure (SBP) in both blacks and whites while a measure of "John Henryism" showed no correlation with blood pressure in either group (P = .81). The findings are consistent with the literature in supporting a connection between anger and blood pressure but do not support the relationship between John Henryism and blood pressure. PMID- 1920519 TI - Access to medical care for black Americans with an episode of illness. AB - Blacks have been directly or indirectly affected by changes in policies such as cutbacks in the Medicaid program or decreases in the funding of graduate medical education. Yet there is considerable disagreement over whether blacks have achieved equity of access to medical care. Descriptive and multivariate regression analyses were conducted to examine the use of ambulatory and inpatient medical care by 1150 whites and blacks under the age of 65 who experienced an episode of illness and lived around sites serviced by the Community Hospital Program, which was developed to increase primary care in underserved communities. After controlling for demographic factors, health status, and aspects of the usual source of care, multivariate analyses revealed that race was not a determinant of differences found in the use of ambulatory and inpatient medical care or the likelihood that an individual was cured of the condition causing him or her the most worry. Differences in the use of care for blacks were believed to have occurred because blacks were disproportionately found in groups that used less medical care, ie, low-income groups, the uninsured, and those without a usual source of care. PMID- 1920520 TI - Factors related to medical school application and acceptance in minority summer enrichment program students. AB - Baylor College of Medicine has conducted a summer enrichment program for minority/disadvantaged premedical students since 1969. Follow-up data on medical school application and acceptance for participants from 1980 through 1984 were analyzed in relation to selected preprogram variables--cumulative college grade point average, total Scholastic Aptitude Test score, competitiveness of undergraduate college, sex, and ethnicity. Results of univariate and multivariate analyses indicated that: 1) females were significantly less likely to apply to medical school than males, 2) females had significantly lower mean MCAT scores (5.9 vs 7.2) even though their preprogram academic performance was comparable to that of the males, and 3) after controlling for MCAT scores, none of the preprogram variables were significant in predicting medical school acceptance. These findings suggest the need for research to explain the discrepancy between male and female MCAT performance and frequency of medical school application in summer program participants. The findings also have implications for the type of counseling provided to female participants in summer enrichment programs. PMID- 1920522 TI - Primary peritoneal pregnancy: a case report. AB - Primary peritoneal pregnancy has been reported and debated for almost a century. Case reports using Studdiford's criteria and later modified criteria have substantiated the entity, but the pathogenesis remains an enigma. This article fulfills both criteria and discusses the factors related to the pathogenesis. PMID- 1920521 TI - Dynamic computed tomography as an ancillary screening test for traumatic thoracic aortic injuries: a critical review. AB - While the divergence of opinion on the matter of diagnostic modalities will probably continue, dynamic computed tomography scans should be considered as a necessary study in assessing a possible traumatic thoracic aortic injury. The use of this modality will decrease the need for thoracic angiograms and invariably increase the yield. PMID- 1920523 TI - An anthropologist's views of the roots of violence in the United States. PMID- 1920524 TI - Postlabeling analysis of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells of foundry workers. AB - Blood samples were obtained from 61 volunteers working in a Finnish iron foundry who were exposed to carcinogenic polycyclic aromatic hydrocarbons and from 19 control subjects not known to be exposed to these chemicals. Foundry workers were categorized into high, medium, or low exposure groups, based on their exposure levels to airborne benzo[a]pyrene (BaP) (high greater than 0.2, medium 0.05-0.2, low less than 0.05 micrograms BaP/m3 air). Aromatic adducts were determined in white blood cell DNA from exposed and unexposed subjects using 32P-postlabeling. There was a highly significant correlation between the estimated exposure and adduct levels as determined by analysis of variance. The levels of adducts found in the high and medium group samples ranged from 5 to over 20 adducts in 10(8) DNA nucleotides. No effects due to age, sex, or the smoking habits of the subjects were observed. Within each group, the SEM appeared rather small. This study demonstrates the utility of the 32P-postlabeling assay to assess human exposure to known and unknown environmental aromatic genotoxicants. PMID- 1920525 TI - Influence of cadmium ions on the reactivity of isolated human uterine arteries. AB - The isometric contractions were recorded for pieces of uterine arteries as well as ascending branches of uterine artery (1-2 mm diameter) obtained from 36 nonpregnant, premenopausal women undergoing hysterectomy. Contractile responses to K(+)-depolarization, noradrenaline, and Ca+2 ions were studied. Cadmium at concentrations 10(-9)-10(-3) M produced no changes of tension in the investigated arteries. Incubation (15 min) with low concentration of cadmium (10(-9)-10(-7) M) evoked an increase of amplitude of K(+)-induced contractions in 50% of investigated vessels. Cadmium at concentrations of 10(-6)-10(-3) M gradually inhibited contractions. The influence of cadmium on contractions evoked by noradrenaline was similar to those on K(+)-induced contractions. In a Ca(2+)-free medium, 10(-5) M cadmium induced tonic contractions and pretreatment with 10(-7) and 10(-5) M cadmium slightly enhanced Ca(2+)-induced contractions. Cadmium concentration of 10(-4) M caused substantial inhibition of Ca(2+)-induced contractions. The results suggest that in the human uterine vessels cadmium is not only a Ca(2+)-channels blocker but also interferes with intracellular mechanisms involved in excitation-contraction coupling. PMID- 1920526 TI - Urinary mutagens in cosmetologists and dental personnel. AB - Cosmetologists are occupationally exposed to a wide range of toxic chemicals both dermally and by inhalation. Since many of these chemicals are mutagens and may be excreted in urine, the Ames Salmonella typhimurium assay was used to determine the presence of direct-acting and promutagens in the urine of practicing cosmetologists in central New York State. A comparable group (age, gender, smokers) of dental hygienists and assistants in the same geographic area was used as the control cohort. The cosmetologists had a significantly higher (39 vs. 24%, p less than .03) frequency of direct-acting urinary mutagens but there was no difference between the groups in the frequency of promutagens. In the multivariate model, cosmetologists were at two times the risk of direct-acting mutagens compared to dental workers. Smoking regularly, within 24 h of taking the urine sample, and the number of cigarettes smoked daily were not associated significantly with direct-acting mutagens in urine. Similarly, having had a hair permanent or hair dyed within 7 d of urine sampling, years of employment, age, gender and use of protective gear were not predictive of direct-acting urinary mutagens. In contrast, employment was not associated with urinary promutagens but the risk was significantly increased with increasing age and cigarette smoking. Among possible adverse health symptoms queried, only the prevalence of skin rashes differed between the cosmetologists (29%) and dental personnel (15%) (p less than .05). PMID- 1920527 TI - Effect of administration of Aroclor 1254 on the activities of hepatic drug metabolizing enzymes in zinc deficiency. AB - In order to understand the mechanisms of carcinogenesis in zinc deficiency, a study was conducted in experimental animals to investigate the effect of administration of an inducer. After the production of zinc deficiency in NIN/Wistar strain of rats by feeding an egg albumin-starch based diet almost devoid of zinc, the animals were administered a potent inducer of mixed-function oxidases: Aroclor 1254 and various Phase I and Phase II enzymes of drug metabolism like benzo[a]pyrene hydroxylase, microsomal epoxide hydrolase, cytosolic epoxide hydrolase, and cytosolic glutathione-S-transferase studied in liver tissues. Control and pair-fed groups were also run alongside. The results showed that while the activities of various enzymes studied were low in the uninduced basal condition, these activities increased many-fold after induction. This induction was observed not only in the control group, but in the pair-fed and deficient groups as well. These results suggest that the ability to respond to a carcinogenic insult, though initially present in zinc deficiency, may not be adequate to counteract an excess or chronic exposure to carcinogen in the long run. PMID- 1920528 TI - Disposition of [14C]furan in the male F344 rat. AB - In a recently completed 2-yr bioassay, furan was found to induce cholangiocarcinomas at high incidence in rats. The disposition of single and multiple gavage doses of [2,5-14C]furan has been determined in male F344 rats to aid in interpretation of that study. In the 24 h after dosing about 80% of the furan-derived radioactivity was eliminated, primarily via urine and expired air. [14C]Carbon dioxide was a major metabolite, indicating that furan ring opening followed by complete oxidation of at least one of the labeled carbons was a major part of the overall metabolism of furan. Liver contained more furan-derived radioactivity by far than other tissues after 24 h. Approximately 80% of the radioactivity in liver was not extracted by organic solvents and was associated with protein. There was either no binding to DNA or the furan-DNA adduct was not stable to the isolation procedure. Repeated daily administration of [14C]furan resulted in a more or less linear increase in covalent binding through four doses; at this point the amount of nonextractable radioactivity plateaus. Urine contained at least 10 metabolites, again indicating extensive metabolism of the furan ring. From the data obtained in this study it is clear that furan is metabolized to reactive species, apparently primarily in liver, and these intermediates react with protein. The hepatotoxicity resulting from furan exposure may be due to the reaction of furan metabolites with liver macromolecules; the presence of some of these reactive metabolites following chronic exposure to furan may result in cholangiocarcinomas. PMID- 1920530 TI - Expression of a novel gene product by transplants of genetically modified primary fibroblasts in the central nervous system. AB - Primary fibroblasts initiated from skin biopsies of Wistar rats were transfected with a plasmid that encodes the human growth hormone and the neomycin resistance genes. Cell clones selected for G418 resistance and expressing high levels of human growth hormone were propagated in vitro and subsequently transplanted into the cerebral cortex of adult allogeneic rats. Grafts were examined by immunocytochemistry at weekly intervals up to 2 months. Fibroblasts in the transplants survived and expressed growth hormone clearly up to 4 weeks, but showed reduced expression at 6 to 8 weeks. Significant levels of human growth hormone were also detected by radioimmunoassay in the serum of the host rats up to 1 month. The experiments demonstrate that primary fibroblasts can be genetically modified to deliver a new gene product into the central nervous system, and the gene product can pass the blood-brain barrier to enter the systemic circulation. This model illustrates the potential to introduce desired products into the brain through the genetic alteration of autologous primary fibroblasts. PMID- 1920529 TI - Enhanced and prolonged pulmonary influenza virus infection following phosgene inhalation. AB - Animal infectivity models have been important in the demonstration of enhanced susceptibility to viral and bacterial infection as a result of low-level toxicant exposure. This study demonstrated an enhanced and prolonged viral infection using an influenza virus infectivity model in the rat following exposure to the toxicant gas phosgene. Fischer-344 rats exposed to either air or a sublethal concentration of phosgene demonstrated peak pulmonary influenza virus titers 1 d after infection. Virus titers in rats exposed to air declined rapidly falling below detectable levels by 4 d after infection. However, a significantly enhanced and prolonged pulmonary influenza virus infection was observed on d 3 and 4 after infection in rats exposed to phosgene. Virus was cleared below detectable limits on d 5 after infection in animals exposed to phosgene. Thus, inhalation of sublethal concentrations of phosgene resulted in an increased severity of pulmonary influenza virus infection. This study provides a demonstration of the effective use of a rat viral infectivity model to detect the immunotoxicity of inhaled pollutants. This model will allow future studies to focus on the immunological mechanism(s) responsible for the enhanced and prolonged pulmonary influenza virus infection. PMID- 1920531 TI - Adhesion and proliferation are enhanced in vitro in Schwann cells from nerve undergoing Wallerian degeneration. AB - Proliferation of Schwann cells during nerve degeneration or regeneration is well documented in vivo. We investigated whether the proliferative response of Schwann cells to injury is retained in vitro. Using 5-month-old male C57BL mice, Schwann cells were isolated from sciatic nerves under 3 experimental conditions: (1) uninjured, (2) after permanent nerve-transection, or (3) after nerve-crush, which permits axonal regeneration. Schwann cells rarely attached to polylysine-coated coverslips when isolated from uninjured or 1 day posttransection/crush nerves. The number of adherent cells increased when Schwann cells were isolated 3 days after nerve-transection or -crush. When cells were isolated from transected nerves, cell adhesion reached a peak 2 weeks after the injury and then declined. Maximal attachment of Schwann cells occurred when the cells were isolated 2-4 weeks after nerve-crush. The percentage of Schwann cells with spreading processes corresponded closely with the number of thymidine-labeled cells at 1 day in vitro. The in vitro capacity of cells to spread and incorporate thymidine reached maximal levels at 5 days posttransection/crush. Capacity of cells to spread and incorporate thymidine subsequently decreased with time following transection. However, a biphasic elevation in cell spreading and thymidine incorporation was observed in Schwann cells isolated from crushed nerves. Maximal growth of Schwann cells in vitro occurred at 1-2 weeks posttransection and at 1-4 weeks postcrush. Adhesion and spreading of Schwann cells were promoted by coating coverslips with laminin or fibronectin. Preincubation of Schwann cells with soluble laminin or fibronectin prevented the initial cell attachment induced by the corresponding protein. Our results suggest that Schwann cells from injured nerves possess binding sites for laminin and fibronectin, which are, in part, responsible for the enhanced adhesion of Schwann cells in vitro. This study provides a new method for preparation of Schwann cells from peripheral nerves of adult mice. PMID- 1920532 TI - Human monoclonal antineurofilament antibody cross-reacts with a neuronal surface protein. AB - Increased titres of anti-neurofilament antibodies have been reported in neurodegenerative disorders, and it has been suggested that such antibodies might be pathogenic. We investigated the specificity of an IgA monoclonal antibody (MAb) from a patient with amyotrophic lateral sclerosis which reacted with neurofilaments and bound to the surface of neuroblastoma cells. In Western blots, the immunoaffinity-purified IgA bound to the 220-kD, high-molecular-weight neurofilament protein (NFH) and cross-reacted with several closely migrating protein bands with apparent mobility of 62-68 kD in neuroblastoma cells and extracts of normal human spinal cord. Following crosslinking to the surface of radiolabeled neuroblastoma cells, the IgA MAb immunoprecipitated a 65-kD protein, indicating that the protein was present on the cell surface and available to the antibodies for binding. Several other MAbs to NFH did not immunostain the surface of neuroblastoma cells or bind to the 65-kD protein, indicating that the protein was not a fragment of NFH. Thus, antibody binding to the 65-kD protein, possibly by cross-reacting with NFH, may have contributed to the neuronal degeneration. PMID- 1920533 TI - Protein kinase C-induced redistribution of the cytoskeleton and phosphorylation of vimentin in cultured brain macrophages. AB - The phorbol ester 12-O-tetradecanoyl-acetate (TPA) induced prominent and transient changes in the organization of the cytoskeleton in cultured amoeboid microglial cells including redistribution of actin toward the center of the cells and in the subplasmalemmal region, appearance of fine actin filaments, retraction of microtubules (MT), and rearrangement of intermediate filaments (IF) containing vimentin. The possible implication of protein kinase C (PKC) in mediating the effects of TPA was suggested by a parallel shift of PKC activity from the soluble to membrane fractions and phosphorylation of several microglial proteins. The rearrangement of IF closely correlated with increased vimentin phosphorylation, detected by pulse labeling of intact cells. Two monoclonal antivimentin antibodies, B3 and V9, showed different staining patterns. Immunoreactivity with the antibody B3 was more restricted and could be abolished by treatment of fixed, permeabilized cells with alkaline phosphatase, thus suggesting that the antibody reacts with a phosphorylated epitope. Using this antibody, rearrangement of IF involving vimentin phosphorylation was detected within 15 to 60 min of treatment with 50 nM TPA and consisted in the appearance of intense perinuclear fluorescent label. This perinuclear fluorescence persisted up to 24 hr after TPA removal and gradually diminished during the following 2 to 3 days. Immunochemical analysis of nonionic detergent-soluble and -insoluble extracts from untreated and TPA-treated cells revealed no differences in vimentin solubility suggesting that TPA induced vimentin phosphorylation does not result in notable vimentin filament disassembly. However the extent of vimentin degradation was more prominent in TPA treated cultures indicating a higher sensitivity of vimentin to proteolytic degradation. The data show that PKC-mediated phosphorylation of vimentin results in precise spatial and temporal rearrangement of IF which are not associated with altered vimentin solubility, but possibly changes the mechanical properties and interactions of vimentin filaments. PMID- 1920534 TI - Distribution of protein kinase C isozymes in rat optic nerves. AB - Light (LM) and electron (EM) microscopic immunocytochemical methods were used to study the distribution of protein kinase C (PKC) isozymes in adult rat optic nerves. In cryostat and vibratome sections examined by LM, type II (beta) isozyme was localized almost exclusively in the axons. In the EM, immunoreaction products were found to associate with microtubules and neurofilaments. The inner surface of axonal membranes were occasionally stained. Analysis of PKC isozyme composition of the optic nerves by using immunoblot techniques revealed that type II (beta) isozyme accounted for approximately 80% of the total immunoreactivity. By contrast, type III (alpha) isozyme, which accounted for the remaining 20% of PKC, was found mainly in the astrocytes. Astrocytic processes next to blood vessels and between myelinated axons were stained. In the EM, immunoreaction products were found in the cytoplasm and along astroglial filaments. Segments of plasma membranes also were stained; but nuclei were unstained. Adult glial cells were not stained by an antibody to type II (beta) isozyme except for the occurrence of a few punctate cytoplasmic densities in occasional astrocytes. Very faint or no immunostaining was observed in sections treated with a monoclonal antibody to type I (gamma) isozyme. Immunoblot analyses also did not reveal this subspecies. The absence of type I (gamma) isozyme in optic nerves is not due to a down-regulation of the enzyme during development. In developing (5 and 11 day) rats, immunoreactivity of protein kinase C was very faint or absent. After 15 days, reaction products of both type III (alpha) and type II (beta) isozymes were found throughout the nerve. These findings suggest that type II (beta) isozyme may be involved in axonal transport whereas type III (alpha) isozyme may play a role in some astrocyte functions in mature optic nerves. PMID- 1920535 TI - Autoradiographic study of iron-binding sites in the rat brain: distribution and relationship to aging. AB - Specific binding of 59Fe to various brain structures was investigated in rats using nanomolar concentrations of 59FeCl3 and quantitative autoradiography. Saturation studies revealed high affinity binding (kd in the nanomolar range) with binding sites density (Bmax) which varied in different brain regions from 462 fmol per mg tissue in the central thalamic nuclei to over 4 pmol per mg tissue in the cerebral peduncle. Binding was seen in both white and gray matter structures. Bmax values for frontal cortex, dentate gyrus, and substantia nigra were significantly lower in older rats. The distribution of 59Fe binding sites was not consistent with the distribution of brain iron as reported by other investigators. 59Fe binding was reduced significantly in the presence of free radicals. These observations suggest that high affinity binding sites for iron are localized differentially in various brain structures and may play an important role in the translocation and storage of potentially harmful ferric cations in brain. The finding that the capacity of the brain tissue to bind iron diminished with age in discrete brain regions suggests that in the aged animal, the removal of "free" iron from the cellular domain may be impaired in such regions, leading to increased susceptibility to iron-enhanced lipid peroxidation and cell death. PMID- 1920536 TI - Cloning of a human cDNA expressing a high voltage-activating, TEA-sensitive, type A K+ channel which maps to chromosome 1 band p21. AB - Over ten different mammalian genes related to the Drosophila Shaker gene (the Sh gene family) have been identified recently. These genes encode subunits of voltage-dependent K+ channels. The family consists of four subfamilies: ShI genes are homologues of Shaker; ShII, ShIII, and ShIV are homologues of three other Shaker-like genes in Drosophila, Shab, Shaw, and Shal, respectively. We report here the cloning of a human K+ channel ShIII cDNA (HKShIIIC) obtained from a brain stem cDNA library. HKShIIIC transcripts express an atypical voltage dependent transient (A-type) K+ current in Xenopus oocytes. This current is activated by large membrane depolarizations and is extremely sensitive to the K+ channel blocker TEA unlike most A-type currents. The gene encoding HKShIIIC maps to chromosome 1p21. PMID- 1920538 TI - Molecular toxicology on cytochrome P-450 in human fetal livers. AB - Among mammalian species, humans and monkeys are sole species which possess cytochrome P-450 in the liver in fetal life. Cytochrome P-450 catalyzes oxidations of a wide variety of compounds including steroids, drugs and toxicants. Thus, the purpose of this study was to examine the toxicological significance of human fetal cytochrome P-450. Firstly, we found that human fetal livers were capable of activating numbers of carcinogenic compounds. Secondly, the capacity of human fetal cytochrome P-450 to activate mutagens and carcinogens was confirmed using purified forms of cytochrome P-450. For this, we purified four forms of cytochrome P-450 from human fetal livers. Lastly, we could isolate a cDNA clone coding for P-450HFLa which is one of the major forms of cytochrome P 450 in human fetal livers. Utilizing synthesized cD-NAs as probes, we found that this form of cytochrome was expressed specifically in fetuses. PMID- 1920537 TI - Oligodendrocytes and myelin sheaths in normal, quaking and shiverer brains are enriched in iron. AB - Early studies employing iron histochemical techniques found a spatially restricted distribution of oligodendrocytes and myelin enriched in iron. In particular, oligodendrocytes and myelin positively stained for iron were found in sparsely myelinated brain regions but not in densely myelinated tracts. Subsequent studies modified the iron histochemical technique and demonstrated that oligodendrocytes and myelin were stained in densely myelinated brain regions but the staining occurred in patches rather than uniformly throughout densely myelinated tracts. This study further modified the iron histochemistry technique to establish that oligodendrocytes and myelin are enriched in iron throughout densely myelinated tracts. This finding supports biochemical studies that detected high levels of iron in white matter (Hallgren and Sourander, J Neurochem 3:41-51, 1958) and myelin fractions of brain homogenates (Rajan et al., Life Sci 18:423-432, 1976). Thus, this histochemical study and earlier biochemical studies indicate that white matter is a major site of iron concentration within the brain. The present study also examined the distribution of iron in oligodendrocytes and myelin from the dysmyelinating mutant mice quaking and shiverer. Results from these studies demonstrate that oligodendrocytes and myelin are enriched in iron in both quaking and shiverer brains. An unexpected finding was an intense staining of oval structures within the oligodendrocyte cytoplasm. This result indicates a concentration of iron in these structures and may be important for understanding how high concentrations of iron are processed by oligodendrocytes. PMID- 1920539 TI - Alteration of aflatoxin B1 metabolic profiles and reduction of aflatoxin B1 mutagenicity by hepatic microsomes of rats fed butylated hydroxyanisole. AB - Effect of administering butylated hydroxyanisole (BHA) on the metabolism of aflatoxin B1 (AFB1) and production of mutagenic metabolites have been compared with those of phenobarbital (PB) and 3-methylcholanthrene (MC) administration in rat liver microsomes. Male Sprague-Dawley rats were treated with these inducers and liver microsomes were isolated. These microsomes were used to metabolize AFB1 and to produce mutagenic metabolites. Results showed that normal rat liver were able to metabolize AFB1 quite actively and produced large amounts of AFB-8,9 epoxide (appearing as the AFB-8,9-dihydrodiol-Tris complex). Upon incubations of normal rat liver microsomes with increasing concentrations of AFB1, a steep dose related increases of mutagenicity was observed in the Ames test. The PB microsomes had an increased ability to metabolize AFB1 and particularly the rate for the production of the weakly mutagenic AFQ1 metabolite was markedly increased. Conversely, PB-microsomes had a moderate decrease in its ability to form the strongly mutagenic of AFB-8,9-epoxide metabolite. However, the ability of PB-microsomes to form mutagenic metabolites from AFB1 was somewhat greater than that of the control-microsomes. The MC-microsomes had an increased ability to metabolize AFB1 also. However, instead of the weakly mutagenic AFQ1 metabolite seen with the PB-microsomes, large amounts of the strongly mutagenic AFM1 metabolite was formed. Although AFM1 is not known to be a direct mutagen, it was highly mutagenic upon activation with microsomes. The very steep dose-related increases of mutagenicity and appearance of bacterial toxicity at relatively lower doses of AFB1 may have been caused by the secondary metabolic activation. The ability of BHA-microsomes to metabolize AFB1 was decreased. Among the metabolites produced by the BHA-microsomes, the non-mutagenic AFB2a was formed in significantly increased amounts but the toxic AFB-8,9-epoxide was produced only in much reduced amounts. The AFB2a was not mutagenic even after metabolic activation with microsomes. When increasing concentrations of AFB1 was incubated with BHA-microsomes, a very mild dose-related increases of mutagenicity was observed and the occurence of toxic effects on bacterial growth appeared only at high doses of AFB1. This may have been due both to the reduced rate of overall AFB1 metabolism and to the decreased formation of the highly mutagenic AFB-8,9 epoxide but an increased formation of the non-mutagenic AFB2a metabolite by the BHA-microsomes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1920541 TI - Sensitive phases for teratogen-induced developmental defects in the brain. AB - Developmental stage-dependent susceptibility to teratogens and sensitive period can be regarded as one of the essential points which characterize teratogenesis. In this paper, emphasis is given to a review of our studies on the critical developmental stage for induction of histogenetic disorders of the cerebral cortex and on the high vulnerability of developing neural cells to teratogenic agents. The undifferentiated ventricular cells in the mammalian fetal telencephalon are particularly vulnerable to various cytotoxic agents at the time when the ventricular cells start to differentiate into cerebral cortical neurons and the cortical plate appears. This period is day 13 of gestation in mice, day 15 in rats and 8 weeks after fertilization in humans. This developmental stage of the brain corresponds to the period of highest sensitivity for induction of cerebral cortical disorders observed postnatally both in laboratory animals and in humans. One of the significant factors determining the period of highest sensitivity of the ventricular cells could be a certain initial phase of cytodifferentiation in G1 and G0 phase cells prior to their actual morphological differentiation. PMID- 1920540 TI - Release of liver microsomal beta-glucuronidase from hepatocytes in vitro and in vivo by organophosphates and hepatotoxic agents. AB - Liver microsomal beta-glucuronidase is stabilized within microsomal vesicles by complexation with the accessory protein, named egasyn. In this study, we showed that egasyn is identical to one of the carboxylesterase isozymes and organophosphorus and carbamate insecticides, acetanilide which is a specific substrate of egasyn and halothane caused a rapid dissociation of the egasyn microsomal beta-glucuronidase complex when administered in vivo or when added in vitro to isolated hepatocytes. The dissociation was relatively specific to organophosphates, carbamates, but not pyrethroids. Dissociation of the egasyn beta-glucuronidase complex in vivo by organophosphates was followed by massive and rapid secretion of microsomal beta-glucuronidase into plasma. From these results, we concluded that release of liver microsomal beta-glucuronidase is the most rapid and sensitive marker to organophosphorus or carbamate insecticide induced intoxication. PMID- 1920542 TI - Neurotoxicity and long lasting analgesia induced by capsaicinoids. AB - Administration of capsaicin (8-methyl-N-vanillyl-6-nonenamide) to neonatal rats gives a long-lasting insensitivity to chemical irritants, and its potential as a specific toxin for peripheral C-fibers has made it of particular interest to neurobiologists concerned with pain mechanisms. The existence of capsaicin receptor on primary afferent sensory neurons is now evident. To deduce a receptor model for capsaicin, and propose the possible molecular interactions at the site of action, we prepared more than 50 capsaicin congeners (capsaicinoids). With these capsaicinoids, we investigated the role of functional groups in producing the long-lasting analgesia by phenylquinone writhing test and Randall-Selitto's method with ICR mice and SD rats. The structure-activity relationship of capsaicin in producing analgesia was established as follows: proper length of hydrophobic alkyl chain is 8-18 carbon atoms; 3-methoxy group of aromatic ring plays an important role but not essential; the presence of phenolic-OH is indispensable and the most suitable site is para-position; acyl amide linkage is dispensable; the linkage of amide bond bridged to the ring with CH2 is appropriate. Depletion of substance P from spinal cord and dorsal horn of rats by capsaicinoids was proved by RIA and immunohistochemistry. We succeeded in eliminating a potent acute toxicity shown by capsaicin through its structural modification. PMID- 1920543 TI - Behavioral teratogenicity of methamphetamine. AB - Pregnant Wistar rats were given daily subcutaneous administrations of methamphetamine (MAPT; varying doses ranging from 1.0 to 4.5 mg/kg) from days 7 to 20 of gestation and teratogenic effects have been determined. The teratogenic effects inducible with orally administered caffeine (90 mg/kg/day) for the same durations were used as the positive controls. MAPT doses greater than 2.0 mg/kg have suppressed the rate of maternal weight gain. Some of the offsprings (F1) of the prenatal MAPT treated groups had decreased growth rate and delayed development of physical characters and functional reflexes. The male offsprings of the MAPT treated groups had significant decreases in their spontaneous motor activity but had enhanced conditioned avoidance responses. However, the mating performances of these offsprings were not affected. These results indicated that prenatal exposure of MAPT may induce some behavioral teratogenicity in rats. PMID- 1920544 TI - Usefulness of medium-term bioassay determining formations of pulmonary adenoma in NIH(GP) mice for finding anticarcinogenic agents from natural products. AB - Various long-term bioassay methods have been used to determine the carcinogenicity of chemical substances. Among them, a long-term method developed by Toth (1968), which scores the incidence of pulmonary adenoma formation at 28 to 56 weeks following subcutaneous administration of chemical carcinogens to new born mice is used widely. This particular long-term bioassay method, while it takes long periods, has proved useful in determining the anticarcinogenic effect of ginseng extracts against the pulmonary adenoma formation inducible with dimethylbenzanthracene, urethane, and aflatoxin B1. More recently, in order to shorten the assay durations to 9 weeks (medium-term), we have modified the existing method by adjusting the doses of carcinogens to be administered to the new-born mice. We have established a modified method in which 40-50% of mice were found to develop pulmonary adenoma 9 weeks after a subcutaneous injection of 0.5 mg/kg to new-born mice of NIH(GP) strain and this modified medium-term bioassay system was found useful in the screening of cancer preventive agents among natural products, such as ginseng and caffeine. PMID- 1920545 TI - Carcinogenic tryptophan pyrolysis products in the environment. AB - The purpose of this study is to evaluate the risk of carcinogenic tryptophan pyrolysis products to human health. During the last decade, a new series of heterocyclic amines has been isolated as potent mutagens and later shown to be potent carcinogens in experimental animals. Among them, 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), carcinogenic tryptophan pyrolysis products, have been investigated from various points of view and useful pieces of information about them have been collected. These carcinogens are widely distributed in the environment such as airborne particles, rain water, cigarette smoke and cooked foods, and they possess various pharmacotoxicological activities such as convulsant activities and potent inhibitory effects on platelet function and dopamine metabolism. Recent investigations revealed that these compounds are present in human samples such as plasma, urine and bile, indicating that humans are actually exposed to these compound. It is a matter of urgency to establish a suitable method for monitoring the exposure levels of these compounds to humans. PMID- 1920546 TI - Characterization and expression of RAD4 gene involved in nucleotide excision repair of UV-damaged Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae express RAD4 gene for nucleotide excision repair of UV induced DNA damages. Upon complementation with rad4-4 mutant, a 7.6 kb clone containing the RAD4 gene designated as pPC1 was isolated from a yeast genomic library. The pPC1 was further narrowed to 2.5 kb flanked with BglII and BamHI sites. The cloned RAD4 gene was found to propagate in E. coli without loss of its complementing activity. Pulse-field gel electrophoresis indicated that the cloned RAD4 gene was localized in the right arm of chromosome V. DNA-tRNA hybridization revealed that the cloned gene did not contain a suppressor tRNA gene. The rad4 mutants with various plasmids containing the cloned RAD4 gene, regardless of their copy number, had enhanced resistance against UV damages equivalent to that found in wild type. As determined by S1 nuclease digestion, the RAD4 transcript was found to be 2.3 kb in size and the S1 nuclease mapping revealed the production of a protected fragment of 760 nucleotides within the transcript. Transcriptional start point was found at 48 base pairs upstream from the first ATG codon of the translation initiation codon. The overexpressed Rad4 protein was estimated to be 89 kD and confirmed the expected size based on the actual length of RAD4 gene. Upon stationary phase culturing, E. coli cells transformed with the cloned RAD4 gene had a delayed entrance into exponential growth phase and produced reduced amount of host proteins. These results have indicated that the pPC1 is a functional RAD4 gene playing a unique role involved in the nucleotide excision repair of yeast without any genetic change during amplication in E. coli. PMID- 1920547 TI - Quantitative evaluation on the genotoxic potency of chemicals. AB - Two in vitro tests with different genetic end points, gene mutation and chromosomal damage, and an in vivo test, preferably the micronucleus test in mice, were recommended as a battery system for the primary assessment of genotoxic effects of chemicals. From our comparative studies on the mutagenic potency of chemicals, it was pointed out that results should be evaluated quantitatively rather than qualitatively, since the potency varies extensively, at range of 10(7) fold, among different chemicals, and the in vitro genotoxins relatively weak tend to be negative in in vivo mutagenicity tests as well as in carcinogenicity tests in rodents. New Salmonella tester strains, called YG series, were established, which showed a high nitroreductase or acetyltransferase activity and specifically sensitive to nitroarens or aromatic anmines in the reverse mutation assays (Ames test). These strains could detect a small amount of mutagenic aromatic amines containing in the urine of cigarette smokers. A new technique in the micronucleus test using peripheral blood erythrocytes was introduced. A cumurative genotoxic effect of benzene, for an example, was detected in the peripheral blood even several weeks after treatment every week by gavage. A cyto-flowmetric analysis can be also applied to monitoring of such effects. PMID- 1920548 TI - The relationship between mechanisms of wounding and principles of treatment of missile wounds. AB - Determinants of the wounding effects of a metallic projectile include the velocity, mass, shape, and stability of the missile, and whether it tumbles, deforms, or fragments within the body. The velocity, mass, shape, and stability influence its capability to penetrate through the skin, and the other factors influence the depth and volume of the wound. The energy lost into the tissues (kinetic energy deposition) is a greater determinant of potential wound volume than is the striking velocity, even though, because K.E. = 1/2 MV2, the potential striking K.E. is more strongly influenced by velocity than mass. The actual size and shape of the wound is influenced by tumbling, deformation, and fragmentation of the projectile and by the characteristics of the tissues and organs contacted. The pulsating temporary cavitation resulting from the passage of a high-velocity projectile produces blunt trauma that extends beyond the tissue actually contacted by the missile. The pulsation of the temporary cavitation with resulting strong negative pressure components permits contamination of the entire wound track of a perforating wound, with entrance of external contaminants from both the exit and the entrance sites. The extent and type of treatment required is determined more by the tissues and organs injured than by the characteristics of the wounding agent. Although extremity wounds from high-velocity projectiles may heal uneventfully, surgical exploration is indicated whenever there is a possibility of subfascial penetration, and obviously devascularized tissue should be excised. In circumstances in which contaminated devascularized tissue cannot be excised promptly or adequately, prophylactic topical antibacterial therapy (such as mafenide aqueous spray, which can penetrate through devascularized tissue) may prevent otherwise lethal infection. PMID- 1920549 TI - Pulmonary contusion causes long-term respiratory dysfunction with decreased functional residual capacity. AB - To elucidate the mechanism of persistent dyspnea after blunt chest trauma, we prospectively studied the pulmonary function of 18 patients with blunt chest trauma for 6 months. Nine of the patients had flail chest and 12 had pulmonary contusion (PC). Pulmonary function was evaluated using spirometry, arterial blood gas analysis, chest x-ray studies and CT scans. Functional residual capacity (FRC) remained significantly reduced throughout the 6 months in patients with PC. Such patients experienced a fall in Pao2 when changed from a sitting position to a supine position and they had fibrous changes in the contused lung as demonstrated by CT scans at 6 months after injury. These findings were supported in an additional study of another 20 patients who had suffered PC 1 to 4 years previously. This study demonstrated that pulmonary function recovered within 6 months in patients without PC even with a residual deformity of the thoracic wall caused by flail chest, while patients with PC had decreased FRC and a fall in Pao2 when moved to the supine position even several years after injury. This might be related to the persistent dyspnea seen after blunt chest trauma. PMID- 1920550 TI - The use of pressure-controlled inverse ratio ventilation in the surgical intensive care unit. AB - A key element in the treatment of Adult Respiratory Distress Syndrome (ARDS) is improvement in oxygen delivery to match metabolic demands. Conventional modes of ventilation have decreased mortality (50%) very little. We have done a retrospective analysis of 30 surgical patients who were treated with pressure controlled inverse ratio ventilation. Mortality was 10%. Arterial oxygenation improved from 40.8 +/- 12.2 mm Hg to 138 +/- 47.2 mm Hg, while PCO2 decreased from 37.8 +/- 7.6 mm Hg to 31.1 +/- 5.9 mm Hg. Simultaneously, with the use of pressure-controlled inverse ratio ventilation, minute ventilation could be decreased by 30%, which may be secondary to increased O2 delivery to the tissue. Our data indicate that pressure-controlled inverse ratio ventilation may be beneficial to surgical patients with ARDS. PMID- 1920552 TI - Functional scoring of multi-trauma patients: who ends up where? AB - To help map the continuum from injury to return to full function, the Functional Independence Measure (FIM) was used in an acute care setting to identify and track disability, to focus rehabilitative efforts during the acute phase of care, and to help demonstrate what is truly important in getting patients back to full functional status. A total of 109 patients were assessed over a 13-month period. FIM scores were based on a patient's ability to routinely perform certain tasks in 18 areas of function and ranged from 1 to 7. The change in FIM scores from admission to discharge was used to determine those patients to be discharged home and those patients to be discharged to a rehabilitation facility. We conclude that the FIM is a very useful tool that produced a very good measure of a patient's total function, tracked progress or lack of it through acute hospitalization, and correctly categorized and quantitated dysfunction (both cognitive and physical) as discharge planning was being done. PMID- 1920551 TI - Five years' follow-up of severely injured ICU patients. AB - We conducted a 5-year follow-up study of a group of 461 consecutive trauma patients treated in our Intensive Care Unit from 1980 to 1983. The entry criteria (initial survival and severe injury: ISS greater than or equal to 18) were fulfilled by 233 patients with a mean ISS of 29.3 and mean age of 35.6 years. Data on prehospital care, type and timing of surgery, and hospital and ICU stay were recorded during hospital discharge. The protocol strictly asked for a personal interview and a physical examination. Mailed questionnaires or phone interviews were not allowed. The areas of medical sequelae, aftercare, missed injuries, occupation, insurance, social integration, economics, legal aspects, and traffic involvement were covered. We were able to gather final information from 223 (95.6%) of the 233 cases. Forty-three patients (18.4%) died in the hospital, 13 patients (5.6%) died later, and 167 (76.5%) were eventually seen. Only 10 patients (4.4%) were lost to follow-up. Outcome was judged using the Glasgow Outcome Scale (GOS), which was compared with a GOS value given prospectively at the time of hospital discharge. Eighty-nine percent of the survivors were healthy or slightly disabled (GOS 5 and 4), 9% were severely disabled, and only 2% were in a persistent vegetative state. Outcome after 5 years was better than tentatively prognosed at the time of hospital discharge. Ninety-one patients with severe head injuries (AIS 4-5) were additionally tested using the Mini Mental State instrument. This test revealed normal mental functions in 77% and dementia, mostly of a minor degree, in 23% of the head injured patients. Almost all the early deaths and two thirds of the late deaths were related to severe head injury. Seventy-nine percent of the survivors were working after 5 years. During the post-trauma period, patients experienced reduced social well-being and also changed professional and recreational activities. There appears to be extensive room for improvement in the posthospital recovery phase. We conclude that survivors of critical trauma have a very good chance, after 5 years, of regaining a high quality of life. All efforts at improving trauma survival and quality of trauma care are therefore worthwhile and deserve high priority. PMID- 1920553 TI - Should survivors with an injury severity score less than 10 be entered in a statewide trauma registry? AB - The necessity of including survivors with minor (ISS less than 10) injuries in a statewide trauma registry with a quality assurance focus was evaluated. During a 3-month period, data for 3,594 admissions to 28 trauma centers were entered into the registry. Of these admissions 1,696 patients (50.8% of patients studied) had an ISS less than 10. Of those, 10 (0.6%) were nonsurvivors and 67 (3.9%) had severe disability (66) or were in a persistent vegetative state (PVS) (1) at hospital discharge. Five nonsurvivors were 65 years of age or older. Four were injured in falls and one was an injured pedestrian. The disabled subset included a high percentage of older patients (61.2% greater than or equal to 55). Minor falls, including those from a bed or chair or from the same level accounted for nearly one half (46.2%) of the disabling injuries. Fifty-one disabled patients had isolated extremity or pelvic fractures. Their hospital stays ranged from 1 to 42 days and averaged 13.0 days. The proportion of elderly in the United States is increasing substantially. Because of the significant risk of death or serious disability to elderly patients, even with minor injuries, we conclude it is appropriate to include data for elderly patients with an ISS less than 10 who meet other registry inclusion criteria. We also recommend the entry of data for patients with an ISS less than 10 and significant disability at discharge who qualify by other criteria. Exclusion of remaining patients with an ISS less than 10 would reduce qualifying cases by 38%. PMID- 1920554 TI - Fibrinolysis in multisystem trauma patients. AB - Changes in the fibrinolytic system may lead to coagulation disorders in acute trauma patients. This study examined fibrin degradation by measuring D-dimer crosslinked fibrin degradation products (indicates hypercoagulability), plasminogen activators (fibrinolysis), and antithrombin III in 42 adult trauma patients and correlated these data with injury severity, types of injury, complications, and clinical tests of coagulation. Hypercoagulability and suppression of fibrinolysis were seen in most patients and were not correlated with severity of injury. These changes appeared most severe in patients with nervous system injury. Several patients with less severe injuries but evidence of hypercoagulability developed clinical evidence of pathologic thrombosis. Latex agglutination of D-dimer provides a rapid test of fibrinolysis that may be clinically useful in the management of trauma patients who cannot be easily studied for thrombosis. PMID- 1920555 TI - Comparison of three methods of rewarming from hypothermia: advantages of extracorporeal blood warming. AB - We developed a new technique, extracorporeal venovenous rewarming (EVR), to rewarm hypothermic patients in the intensive care unit or operating room. We compared this method with the active external (standard) techniques of warming blankets; heated ventilator circuits, intravenous fluids, and gastric and peritoneal lavage; and cardiopulmonary bypass. The EVR technique warmed patients' blood or additional blood products and crystalloids to 40 degrees C at 150-400 mL/min and allowed survival from a core temperature of 31.1 degrees C after massive injury. The EVR technique rewarming patients more rapidly than standard techniques and may be most appropriate in patients with multisystem trauma when rapid correction of hypothermia-related hypovolemia, coagulopathy, and arrhythmia is necessary. Cardiopulmonary bypass is required in severely hypothermic patients with cardiac arrest. Standard techniques can be used when these immediately life threatening conditions are not present. PMID- 1920556 TI - Obesity and increased mortality in blunt trauma. AB - To determine the effect of admission body weight on blunt trauma victims, a chart review of all patients greater than 12 years of age admitted to Sentara Norfolk General Hospital between January 1 and July 31, 1987 was undertaken. The charts of 351 patients were reviewed; 184 records contained admission height and weight. These 184 patients made up the study group and age, gender, injuries, Injury Severity Score (ISS), ventilator days (VD), complications, length of stay (LOS), and outcome were noted. Body Mass Index (BMI) (weight (kg)/(height(m))2, was calculated for each patient. The average ISS was 21.87 (range, 1-66) and the average BMI was 25.15 kg/m2 (range, 16-46 kg/m2). The overall mortality for the population was 9%. The population was grouped according to BMI: average (less than 27 kg/m2), overweight (27-31 kg/m2), and severely overweight (greater than 31 kg/m2). The mortality of 5.0% and 8.0% in the average and overweight groups was not different. The severely overweight group had a higher mortality at 42.1% compared with the other two groups (p less than 0.0001). The groups did not differ in age, ISS, LOS, nor VD. Age, BMI, and ISS were subjected to regression analysis. By this method BMI and ISS were independent determinants of outcome (p less than 0.0001). There was an increase in complications, mainly pulmonary problems, in the SO group (p less than 0.05). The three groups were subdivided into survivors and nonsurvivors. The nonsurvivors had a longer average LOS at 26.6 days compared with nonsurvivors in the overweight (5.0 days) or severely overweight (8.62 days) groups (p less than 0.007). The severely group was characterized by a rapid deterioration and demise that was unresponsive to intervention. ISS did not differ among nonsuvivors. Among survivors the severely overweight group had a lower ISS, 9.73. This was different from the overweight group (21.57) and from the average group (20.21) (p less than 0.04). PMID- 1920557 TI - Unexpected death on the non-ICU trauma ward. AB - To characterize trauma patients who die unexpectedly on the ward (unexpected ward deaths = UWDs), 1,011 trauma-related deaths occurring at a level I trauma center over a 10-year period were reviewed for location of death. Seventy-four deaths occurred on the non-ICU trauma ward (i.e., nonmonitored med-surg floor). Fifty patients were "do not resuscitate" (expected deaths). Twenty-four patients (mean age, 58.0 years) died unexpectedly (2.4% of trauma-related deaths). The majority had a central nervous system injury or a precipitating event that occurred at night. Twelve (50%) of the UWDs were determined by peer review to be potentially preventable and were the result of delayed diagnosis (n = 6), aspiration (n = 3), or cardiorespiratory arrest (n = 3). We conclude that unexpected trauma center deaths related to events occurring on the non-ICU trauma ward (2.4% of trauma deaths) occur mostly at night in older, neurologically impaired patients and that half of these deaths may be potentially preventable. Increased awareness of this issue and an environment for direct patient observation may reduce the number of these potentially preventable deaths. PMID- 1920558 TI - An assessment of time following trauma resuscitation: the transitional evaluation and monitoring phase. AB - Trauma resuscitation for 431 major trauma patients averaged 24 +/- 0.61 minutes. Further analysis of the care of 350 of these patients documented a transitional evaluation and monitoring phase (TEMP), with a physician and nurse in attendance, for an additional 158 +/- 12 minutes until arrival at the operating room, surgical intensive care unit (SICU), hospital ward, or discharge. The duration of TEMP did not vary according to severity of injury (R2 = 0.02). Arrival time (days: 167 +/- 23 minutes; evenings: 142 +/- 13 minutes; and nights: 147 +/- 30 minutes) had minimal effect on TEMP duration. The TEMP for 67 patients undergoing an operation was significantly less than for patients admitted to the hospital ward or SICU (112 +/- 19 minutes vs. 171 +/- 20, p less than 0.05). These 350 patients underwent 582 activities during TEMP including radiologic evaluation (265), CT scan (173), and other activities (144). Extrapolating TEMP time for the 1,800 major trauma patients seen annually, this represents 4,740 hours each of nursing and physician time. A better understanding of TEMP is needed to provide appropriate support and organization during this critical period of trauma care. PMID- 1920559 TI - Effects of intoxication on the catecholamine response to multisystem injury. AB - In patients suffering isolated head trauma, we have previously shown that levels of circulating catecholamines obtained within 48 hours of trauma correlate with the severity of brain injury and predict outcome and that intoxication blunts this response. The effects of alcohol on the increase in catecholamines in systematically injured patients, however, have not been well defined. From 1983 to 1990, 78 patients (74% male; median age 30 years) with blunt head and multisystem injury, who also had alcohol levels measured within 5 hours of injury, were studied. Norepinephrine and epinephrine levels were assayed by a radioenzymatic technique. Injury severity was assessed by the admission Glasgow Coma Scale (GCS) score (4-15; median, 12), the Injury Severity Score (ISS) (13 50; median, 25) and the volume of blood products administered within the first 24 hours (0-14.4 L; median, 0.5 L). The impact of alcohol on the norepinephrine response to injury was analyzed using multiple linear regression models, including polynomial interaction terms. Norepinephrine levels significantly (p less than 0.0001) correlated with the GCS score and ISS. However, alcohol significantly lowered the norepinephrine response to decreasing GCS score (R = 0.49, p less than 0.002) and to increasing ISS (R = 0.51, p less than 0.0006). The blunting of the catecholamine response was most marked in those severely injured. The rise in norepinephrine concentrations seen with increasing volume of blood replacement was not affected by intoxication. An association between injury severity and epinephrine levels was also present, but not as consistently. Epinephrine concentrations rose with falling GCS score and with increasing ISS values, but unlike norepinephrine, there were no apparent effects of alcohol on changes in epinephrine levels. Thus, in patients suffering head and multisystem injury, catecholamine changes reflect the severity of injury using three different scalers. Furthermore, intoxication blunts only the norepinephrine component of this important biologic response. PMID- 1920561 TI - Four types of venous flaps for wound coverage: a clinical appraisal. AB - Venous flaps were used for coverage of hand wounds over exposed bones, joints, and tendons in 28 patients. Four types of operations were performed. Among them type IV was the best. It included the advantages of perfusion in types I and III, but excluded their disadvantages. The viability of venous flaps was confirmed. Clinical observation showed that a venous flap is not merely a composite graft. The presence of a vascular network in the flap helps to ensure initial survival before the establishment of neovascularization between the venous flap and the recipient site. Partial loss of a flap was observed in two cases and complete failure was seen in one case. Viability versus flap size and modality of perfusion are analyzed. With total venous perfusion, small venous flaps usually survive better than large ones. For large venous flaps, arterialized venous perfusion is better than total venous perfusion. Venous flaps are useful for wound coverage of fingers and hand, but they do not replace cross-finger flaps or other conventional flaps when these simpler flaps are available. PMID- 1920560 TI - Continuous arteriovenous hemofiltration countercurrent dialysis (CAVH-D) in acute respiratory failure (ARDS). AB - The balance between intravascular volume, oxygen transport, and arterial oxygenation is delicate in patients with adult respiratory distress syndrome (ARDS). Recently, we used continuous arteriovenous countercurrent hemodialysis (CAVH-D) in 14 nonoliguric patients who had severe ARDS. The cause of the ARDS was pancreatitis in 1 patient, trauma in 10 patients, and postoperative in 4 patients. All patients were edematous, in marked positive fluid balance but not intravascularly overloaded before institution of CAVH-D. Transfemoral CAVH-D was instituted and managed by the SICU staff. Patients underwent CAVH-D for a mean of 65.2 hours (range, 12-140 hours) and cleared a mean of 480 mL/h of filtrate. The only complication was one patient who bled from a loose tubing connection. Three patients were grossly unstable when CAVH-D was begun. Their mean cardiac index (CI) was 2.3 L/min/m2 despite maximal inotropes. Their CAVH-D filters cleared a mean of 600 mL/h, but they required constant fluid resuscitation and died of cardiogenic shock and ARDS within 3 days. The other 11 patients had significant improvement in their respiratory function. Mean FI02 was weaned from 0.73 to 0.45 (p less than 0.005) and PEEP from 14.3 cm to 8.9 cm (p less than 0.005). Peak airway pressures fell from a mean of 60 mm Hg to 45 mm Hg (p less than 0.01). There was no significant change in CI or wedge pressure, but oxygen consumption rose from a mean of 279 to 409 mL/m (p less than 0.05). The technique of CAVH-D offers an alternative to patients with ARDS who do not have large on-going fluid requirements. It is safe, can be managed by the surgical staff, and is associated with a significant improvement in respiratory variables without requiring a drop in filling pressures that might potentially compromise oxygen transport. PMID- 1920562 TI - The argon beam coagulator provides rapid hemostasis of experimental hepatic and splenic hemorrhage in anticoagulated dogs. AB - The argon beam coagulator (ABC) delivers radiofrequency electrical energy to tissue across a jet of argon gas, providing noncontact, monopolar, electrothermal hemostasis. This study compared the efficacy of the ABC with conventional techniques for control of traumatic hepatic and splenic hemorrhage. Standardized lacerations were made to the liver and spleen of 6 heparinized dogs. Control of bleeding was attempted with the ABC (150 W), the Nd:YAG laser (90 W, noncontact), horizontal mattress suture, microcrystalline collagen, and regenerated cellulose. If bleeding had not been controlled within 3 minutes, coagulation was attempted with the ABC in order to prevent exsanguination. Tissue from both the liver and spleen was assessed histologically for damage induced by the ABC. Delayed injury and early healing after ABC coagulation was studied in six additional dogs killed 1 and 3 weeks postoperatively. The ABC stopped bleeding from 25/25 hepatic lacerations in 48 +/- 8 seconds (mean +/- SEM) and from 18/18 splenic lacerations in 28 +/- 3 seconds. The Nd:YAG laser, mattress sutures, and topical hemostatic agents failed to control bleeding in 14 of 15 applications after 3 minutes. The ABC successfully salvaged all failures in less than 1 minute. The depth of splenic and hepatic thermal injury with the ABC ranged from 2 to 7 mm and was proportional to the duration of application. Postoperatively wound healing progressed normally without bleeding or infection at the coagulation site. The ABC appears to be a excellent instrument for achieving hemostasis in solid organ injury, and may be especially valuable in managing patients with coagulation deficits. PMID- 1920563 TI - The biomechanics of lower abdominal steering-wheel loading. AB - Twenty-five fully anesthetized swine were tested for biomechanical responses to lower abdominal steering-wheel loading. Supine subjects were impacted with the lower rim of a segmented steering wheel in a ventrodorsad direction at approximately the L-4 level of the lumbar spine. Peak force ranged from 0.13 to 8.56 kN, peak stroke from 16.1 to 123.8 mm, and peak velocity from 1.7 to 12.4 m/s. Mechanical response is presented in terms of force-deflection cross plots of force-time and displacement-time histories. Overall stiffness, normalized for equal stress-equal velocity scaling using a standard human cadaver mass, was found to be rate dependent and corridors are suggested. These findings indicate that the stiffness of the lower abdomen is less than upper abdominal stiffness and significantly lower than chest stiffness, although lower abdominal stiffness in living subjects is still slightly higher than it is in the lower abdomen of human cadavers. The maximum viscous response (VCmax) was a strong predictor of injury risk for the entire data set. PMID- 1920564 TI - Profound hypothermic circulatory arrest for the management of a penetrating retrohepatic venous injury: case report. AB - Injury to the retrohepatic vena cava and hepatic veins carries with it a very high mortality rate. This type of injury is fraught with difficulty because of poor exposure and uncontrolled bleeding. Various techniques for the management of these injuries have been reported. We describe the use of profound hypothermic circulatory arrest to facilitate repair of penetrating injury to the retrohepatic vena cava and hepatic veins. PMID- 1920565 TI - Ipsilateral open fracture of the femur and tibia treated using the dynamic ASIF BM tubular external fixator: case reports. AB - Two cases of ipsilateral open fracture of the femur and tibia treated using the dynamic ASIF-BM tubular external fixator are described. Results were very good, with short periods of occupational disability. These cases support primary stable osteosynthesis of these simultaneous fractures and the value of dynamic axial external fixation as a definitive treatment of open fractures of the femur and tibia shaft, either isolated or simultaneous. PMID- 1920566 TI - Unusual volar dislocation of the lunate into the distal forearm: case report. AB - A case of a severe wrist injury (fractures of the scaphoid, capitate, hamate, and ulnar styloid process) with volar dislocation of the lunate into the soft tissues of the forearm is presented. This degree of displacement of the lunate is exceedingly rare, and we believe has not been previously reported. Possible mechanisms, hyperextension injury forcing the lunate forward out of the carpus, or contact between the volar wrist skin surface and another object or surface propelling the dislocated lunate into the forearm, are discussed. PMID- 1920567 TI - Late reconstruction of the patellar tendon: case report with a new method of repair. PMID- 1920568 TI - Delayed cardiac tamponade after blunt chest trauma: case report. AB - A case of cardiac tamponade without evidence of hemopericardium within 2 weeks after blunt chest trauma is reported. The cause was a pericardial effusion that may have resulted from the post-cardiac injury syndrome. Pericardiotomy drained 600 mL of straw-colored clear fluid. A high index of suspicion for cardiac tamponade must be maintained in such patients for weeks after injury. PMID- 1920569 TI - Prehospital administration of fluids on survival in trauma patients. PMID- 1920570 TI - Air pollution illnesses: overview and challenge. PMID- 1920571 TI - Indoor air pollution: an edifice complex. AB - The collision of escalating technological sophistication and surging environmental awareness has caused the reexamination of many societal paradigms. Horror stories about lethal chemical exposures involving isolated cases of ignorance, carelessness or greed have caused the public to demand constant vigilance to prevent exposure to potentially hazardous substances. Accordingly, much time and resource has been expanded by the U.S. government and citizens to abate and prevent air and water pollution. While these efforts have met with measurable success, there is increasing public concern about a new generation of pollution-related human illness in office, home and transportation environments. New instances of Sick Building Syndrome or Building Related Illness are reported daily by the popular press. Human health effects such as cancer, infectious disease, allergy and irritation have been ascribed to indoor air pollution. The clinical aspects of indoor air pollution are often discounted by consulting engineers and industrial hygienists involved in indoor air quality. Physicians and clinically-trained scientists have received a "Macedonian call" to sift clinical relevance from the emotional aspects of indoor air quality problems. Point sources of pollutants, associated human health effects, and problem solving approaches associated with indoor air pollution are described. Regulatory and litigational aspects of indoor air pollution are also discussed. PMID- 1920572 TI - Air pollution: the pathobiologic issues. AB - In defining the adverse effects of ambient levels of ozone on the human lung, research has tended to emphasize direct cause and effect responses. However, disease is generally multicausative and the lung has relatively few ways to respond to injury. Moreover, all adult lungs have some disease. Thus, pathogenesis is more appropriately addressed by asking "What role does the agent in question play in the causation, promotion, facilitation, and/or exacerbation of disease that is present?" Our recent studies of the lungs of 107 ostensibly healthy youths between 14 and 25 years of age (violent death cases in Los Angeles County) add suggestive evidence to epidemiologic and experimental data indicating that air pollution is adversely affecting the human lung. We found 80% of the youths with some degree of presumably subclinical Centriacinar Region disease and, in 27%, the Centriacinar Region disease was severe and extensive. Centriacinar Region disease has been linked to infectious organisms, cigarette smoke, ozone, mineral dusts, and other noxious agents. Recently, a mild form of Centriacinar Region disease has been produced in primates exposed to a level of ozone (0.15 ppm) that is frequently exceeded in Los Angeles. Since there is suggestive evidence that air pollution in Los Angeles increases the rate of decline of lung function, we suspect that there has also been an increase in the rate of structural decline, manifest in part by accentuated Centriacinar Region disease. The health significance of Centriacinar Region disease is just beginning to be appreciated. At the very least, reserve depletion reflected in the Centriacinar Region disease implies some reduction in lung performance and some increase in susceptibility to disease in general. At worst, the unexpected severity of the Centriacinar Region disease may be a bellwether for an impending rise in clinically manifested lung disease for the general population. An urgent research need is the monitoring of health through inventories of the functional and structural units of the human lung, with special emphasis on subpopulations of cell societies of the lung. The feasibility of applying image analysis for large volume objective quantitations has been demonstrated and should be implemented. Multicity studies, in cooperation with Offices of the Medical Examiner-Coroner and autopsy services in general, can help meet the critical need for increased sensitivity in the monitoring of the public health in a changing environment. PMID- 1920573 TI - Air pollutants and the respiratory system: toxicity and pharmacologic interventions. AB - Air pollution remains a major aggravation of respiratory symptoms and disease. Sulfur dioxide, ozone, sulfuric acid, particulate matter such as the fine particles from wood smoke, and nitrogen dioxide all produce significant effects when investigated in laboratory or field studies. These effects are decreases in pulmonary function and evidence of inflammation as well as suggestions of increases in chronic respiratory disease. Asthmatic subjects may be the group at greatest risk from air pollutants. Common medications used to treat asthma have varying effects on blocking or mitigating these pollutant-induced effects. PMID- 1920574 TI - Changes in vocal resonance and nasalization following adenoidectomy in normal children: preliminary findings. AB - The purpose of this study was to evaluate changes that occur in certain aspects of vocal resonance and nasalization following adenoidectomy. Fourteen normal children were assessed prior to adenoidectomy and then at one month, three months, and six months following surgery. A unique combination of aerodynamic, acoustic, and perceptual measures were made. The aerodynamic component of the evaluation involved the use of posterior rhinomanometry to calculate nasal airway resistance (Rnaw) during relaxed nasal breathing. Acoustical measures consisted of "nasalance" scores (oral/nasal acoustic ratio) obtained during production of various speech stimuli. In addition, perceptual measures of change in vocal quality included listener judgments of severity and categorical ratings of nasality. Consistent patterns of change in vocal resonance and nasalization following adenoidectomy were identified. Clinical implications of these preliminary findings suggest that the maximum increase in nasality after tonsillectomy and adenoidectomy occurs at about one month, and referral to a speech-language pathologist should be considered if the hypernasality persists beyond three months. PMID- 1920575 TI - Kaposi's sarcoma of the intra-parotid lymph nodes in AIDS. AB - Kaposi's sarcoma is the most frequent malignancy associated with AIDS. The occurrence of Kaposi's sarcoma in the parotid region is extremely rare. In this publication we present a case of a 47-year-old male patient who developed a swelling of the left parotid tail that proved to be Kaposi's sarcoma of an intra parotid lymph node. A discussion of the etiological factors, clinical staging and management of KS, as well as the differential diagnosis of the parotid enlargement in AIDS patients, is presented. PMID- 1920576 TI - The large vestibular aqueduct syndrome and sensorineural hearing loss in the pediatric population. AB - Sensorineural hearing loss, associated with a dilated vestibular aqueduct, is often described as progressive. Since 1982, computed tomography of the mastoids has become part of the routine investigation of deaf children at Sainte-Justine Hospital. Using clinical, audiometric and radiological material from 130 patients with sensorineural hearing loss, we identified 18 patients with enlarged vestibular aqueducts. The large vestibular aqueduct population was then compared to the normal vestibular aqueduct patients in regard to the degree and evolution of the sensorineural hearing loss. Progression of hearing loss was noted in 46% of patients in the presence of large vestibular aqueducts as compared to 35% in the absence of this anomaly. Normal radiographic findings did not exclude the possibility of further hearing loss. PMID- 1920577 TI - Persistence of the foramen of Huschke in the adult: an osteological study. AB - The foramen of Huschke, which appears during the embryological development of the tympanic bone, usually closes by the age of five years. A review of 377 dried skulls revealed that the foramen of Huschke was present in adult life in 7% of the skulls examined. A patent foramen of Huschke in the adult may, in rare cases, be the cause of temporomandibular joint herniation or fistulization through the anterior wall of the bony external canal. PMID- 1920578 TI - Hairy polyp of the eustachian tube. AB - The hairy polyp of the nasopharynx is a rare but potential cause of airway obstruction in the newborn. A case of hairy polyp arising off the Eustachian tube is reported. Only eight prior cases of Eustachian tube origin have been described in the literature. The terminology and embryology of these tumors are included in the discussion. The site of the tumor and histopathology of this case supports the embryologic origin of a congenital inclusion cyst. PMID- 1920579 TI - Otologic manifestations of pseudotumor cerebri. AB - Otologic manifestations of pseudotumor cerebri heightened awareness of pseudotumor cerebri and its varied subtle presentations will allow for a more expedient diagnosis by the otolaryngologist. Pseudotumor cerebri is defined as increased intracranial pressure and papilledema without a mass lesion or obstruction of the ventricular system. Presenting symptoms most commonly are headache and visual dysfunction. However, patients may present with associated symptoms of tinnitus, dizziness and hearing loss. These patients may be seen first by the otolaryngologist. Fourteen patients with a diagnosis of pseudotumor cerebri are reviewed. Nine of the 14 patients had neurotologic symptoms during the course of their evaluation. Pseudotumor cerebri is a diagnostic challenge. Keys to diagnosis are a high index of suspicion, careful history and funduscopic examination in patients with unexplained neuro-otologic symptoms. PMID- 1920580 TI - Acinic cell carcinoma of the parotid gland: review and management. AB - The purpose of this retrospective review is to study the management of a rare malignant tumor of the parotid gland, the acinic cell carcinoma. Incidence, pathology, clinical findings, and diagnosis are reviewed. Twenty-five patients were seen at the British Columbia Cancer Agency (BCAA) for initial treatment, recurrent disease or follow-up during the period 1958-1990. Twenty-two acinic cell carcinomas (ACC) occurred in the parotid gland. Surgical treatment regimens for parotid ACC ranged from local excision to radical excision. Local excision is not advised but superficial parotidectomy alone appears to have been adequate treatment for small superficial tumors. Eleven of 22 patients received radiotherapy. Indications for adjuvant postoperative radiotherapy are given. Nine patients with primary tumors treated with combined therapy are alive and disease free with a mean follow-up of 10.7 years. Postoperative radiotherapy appears to be effective in eradicating microscopic residual disease although long-term follow-up is necessary to make these results clinically significant. PMID- 1920581 TI - Evaluation of conscious sedation in facial plastic surgery. AB - Local anesthesia and conscious sedation are important aspects of facial plastic surgery. The safe and effective application of these techniques is important to produce happy, satisfied patients as well as good surgical results. Local anesthetic and sedative drugs will be discussed with respect to their mechanisms of action, doses, toxicities and appropriate selection. We will discuss the techniques we have developed using fentanyl and Versed and our evaluation of their effectiveness. Twenty sequential facial plastic surgical patients undergoing a total of 30 procedures will be reviewed. The average dose of fentanyl was 70 mcg and Versed was 3.1 mg. Significant amnesia occurred in 60% of patients, 80% experienced little or no discomfort and 90% would have no hesitation to undergo another procedure with similar anesthesia and sedation. PMID- 1920582 TI - Anti-neutrophil cytoplasmic antibodies (ANCA): a seromarker for Wegener's granulomatosis. AB - Wegener's granulomatosis can be a difficult diagnosis to establish. It is not uncommon to require repeated biopsies over many months for histologic confirmation. A recently developed seromarker--anti-neutrophil cytoplasm antibody -ANCA (synonymous with anticytoplasmic autoantibody--ACPA) adds a new and valuable tool for diagnosis. The literature shows this to be a highly specific and sensitive test for Wegener's granulomatosis. PMID- 1920583 TI - The use of fibrin tissue glue in thyroid surgery: resource utilization implications. AB - Current hospital resource limitations prompted efforts to shorten the postoperative in-hospital recovery time after thyroid and parathyroid surgery by hastening the removal of wound drains. Thirty patients' wounds were closed with fibrin tissue glue (Tisseel) and sutures. These were retrospectively compared with 30 randomly selected patients undergoing identical procedures and standard suture closures. Mean drainage the first postoperative night was 18 ml in the test group versus 39 ml in the controls. The average times to drain removal were 1.6 days and 2.2 days respectively. The mean test postoperative hospital stay was reduced by 0.9 days in test patients (2.8 days versus 3.7 days). There was no difference in the complication rate between the two groups. Using this technique, significant increases in the efficiency of resource utilization appear to be possible. A randomized prospective trial of fibrin glue versus traditional closure is required at this time to verify the usefulness of fibrin tissue glue in thyroid surgery. PMID- 1920584 TI - Infection of Waldeyer's ring: value of pernasal retropharyngeal swabs. AB - The value of pernasal retropharyngeal swabs in chronic adenoid and tonsillar disease was assessed in a prospective study involving 52 patients. Prior to adenoidectomy (34 patients) or adenotonsillectomy (17 patients), pernasal and tonsillar swabs were taken and the culture compared to the bacteriology profile obtained in the adenoid and tonsil tissue following surgery. The pernasal swab correctly identified 76% of pathogens isolated in the adenoid tissue. In addition, pernasal swabs forecast the presence of pathogens in 64% of core tonsil specimens, compared to an accuracy of 38% when superficial tonsil swabs were compared to the microbes in the deep tonsil. H. influenzae was the predominant organism isolated in all cultures. Our results clearly demonstrate that pernasal swabs give a representative picture of the adenoid bacterial content. Pernasal swabs are also superior to superficial tonsil swabs in indicating the deep tonsillar organisms. PMID- 1920585 TI - Head and neck cancer localization with indium labelled carcinoembryonic antigen: a pilot project. AB - Antibodies reacting with cancer cells are playing an increasing role in cancer detection. Most antibodies under study are directed at onco-fetal proteins, principally carcino-embryonic antigen (CEA). In terms of imaging, most work has concentrated on the abdominal and pelvic regions. Although the majority of primary head and neck cancers are amiable to clinical identification, detection of regional metastases and recurrences following radiotherapy can be difficult. Antibody to CEA was radiolabelled with Indium-111 and used to identify proven head and neck tumors by external imaging. In seven patients with squamous cell tumors, five of five primary sites and two of three secondary sites were imaged satisfactory. Comparison with conventional scanning showed good correlation. There were no false positive scans, no consistent relationship between serum or tissue CEA levels and the success of imaging was evident. The success of this pilot study should encourage the search for more tumor-specific antigens, and further studies of external scintigraphic techniques in the localization of head and neck cancers. PMID- 1920586 TI - The CT appearance of cricoid chondrosarcoma. PMID- 1920587 TI - Transperineal sonography in second trimester to term pregnancy and early labor. AB - We studied the diagnostic potential of transperineal sonography in 184 pregnant women from midtrimester to term pregnancies and at early labor. In 65 patients in false labor, we established cervical effacement and dilatation. We confirmed the clinical diagnosis of premature rupture of the membranes (PROM) in 27 cases and assessed the placental relationship with the internal cervical os in 20 patients. In 61 women in early labor we measured cervical dilatation, and in 11 patients we looked for details of fetal anatomy. Adequate diagnostic information was obtained in 180 cases (97%). Our results and data from the literature suggest that transperineal sonography is the imaging technique of choice in the situations we studied. PMID- 1920588 TI - Measuring coronal biparietal diameter. PMID- 1920589 TI - Uterine inner myometrial echogenic foci. Relationship to prior dilatation and curettage and endocervical biopsy. AB - The frequent presence of small echogenic foci within the inner myometrium in women who have had prior uterine instrumentation is reported. Bright foci were observed in 35 of 80 patients who had had prior dilatation and curettage or endocervical biopsy and in only 2 of 174 patients who gave no history of either procedure (P less than 0.005). These foci tend to be small (3 to 6 mm), linear, usually nonshadowing, single or multiple, and located immediately adjacent to the endometrium anywhere along the length of the endometrial cavity; they can be seen many years after the procedure was performed. The histopathologic features of these foci are unconfirmed, but we suspect they represent calcification or fibrosis at sites of mechanical injury to myometrium. The presence of these foci serves as a marker of prior instrumentation and probably has no clinical significance. However, sonographers who are aware of their possible occurrence, can avoid mistaking them for leiomyoma calcifications or for air in the endometrium or myometrium in patients with suspected endometritis. PMID- 1920590 TI - Utility of duplex ultrasound in the diagnosis of asymptomatic catheter-induced subclavian vein thrombosis. AB - Asymptomatic thrombosis of the subclavian vein is common after placement of indwelling catheters. The sequelae of these thrombi are not known. Investigation is hampered by the requirement for venography for diagnosis; consequently, a noninvasive method of diagnosis would be welcome in this context. We have studied prospectively 32 subclavian catheters to determine the usefulness of duplex ultrasound in diagnosing asymptomatic thrombosis. Sixteen arm venograms were normal and all gave normal duplex scans. No false-positive scans were obtained. Eleven venograms demonstrated nonocclusive mural thrombi. Only three of these were seen with duplex ultrasound. Five totally occlusive thrombi were seen on venography, of which only two were detected with duplex sonography. The three thrombi not found with duplex ultrasound were short proximal venous occlusions. The insensitivity of this technique to asymptomatic subclavian thrombi limits its usefulness as a screening tool. PMID- 1920591 TI - Endovaginal sonographic diagnosis of ectopic twin gestation. AB - Endovaginal sonography has permitted earlier diagnosis of ectopic pregnancy. Twin ectopic pregnancy is rare. Until now, antenatal diagnosis of twin ectopic pregnancy using endovaginal sonography had not been reported. Three cases of twin ectopic pregnancy diagnosed via the intracavitary probe are presented. PMID- 1920592 TI - Amniotic sheets: natural history and histology. AB - Eleven amniotic sheets were detected on obstetric ultrasound. Ten of these were reviewed retrospectively and one was followed prospectively throughout gestation. Amniotic sheets are single, planar reflective membranes. Evidence presented here suggests that these membranes are composed of four distinct layers: two layers of chorion sandwiched between two layers of amnion. Their mean thickness is 2.4 mm in the midportion and 4.5 mm at the free edge. A thick triangular base is frequently seen. Amniotic sheets change little during pregnancy; however, they are more difficult to identify late in gestation. They are unassociated with fetal anomalies. Mothers with amniotic sheets had a substantial incidence of previous spontaneous or therapeutic abortions. PMID- 1920593 TI - Quantitative sonographic parameters as a means of distinguishing breast cancers from benign solid breast masses. AB - Ultrasound examinations of solid breast masses were reviewed retrospectively to determine whether quantitative data of their dimensions could distinguish benign from malignant tumors. Forty-nine fibroadenomas and 30 carcinomas with cytologic or histologic proof were identified. No significant difference was found between carcinomas and fibroadenomas when comparing the average ratio of length to anteroposterior (L/AP) diameter or the mean ratio of anteroposterior diameter to transverse diameter (AP/T). In this limited series, quantification of the degree of mass elongation along the natural breast tissue planes had low sensitivity in distinguishing malignant from benign tumors. PMID- 1920594 TI - Variation in the size and number of stone fragments after gallbladder lithotripsy. AB - Ninety-four gallbladder ultrasound examinations were carried out in 11 patients at intervals for the first 40 days after lithotripsy. No dissolution or other active therapy was carried out during this time. Fragment size and number were measured to determine the postlithotripsy variability. Analysis of variance (ANOVA) showed no significant changes in fragment size or number over time. The changes in fragment size and number compared to the previous measurements were then evaluated. Again, ANOVA showed no significant changes between times. The average change in absolute size was 3.1 +/- 0.6 mm, and the average change in absolute number was 1.4 +/- 0.5. We conclude that fragment size and number as determined by ultrasound do not vary significantly with time during the first 40 days. The absolute size change measured to the nearest millimeter should be at least 4 mm to surpass the 95% confidence interval. Similarly, the absolute change in number should be at least 2 to be regarded as significant. PMID- 1920595 TI - Definitive prenatal diagnosis of monoamniotic twins. Swallowed amniotic contrast agent detected in both twins on sonographically selected CT images. PMID- 1920596 TI - Peripheral hypoechoic rim of the fetal heart. PMID- 1920597 TI - Simple adrenal cysts in fetus, resolving spontaneously in neonate. PMID- 1920598 TI - Extra-amniotic pregnancy. PMID- 1920599 TI - The role of neutrophil-activating mediators in canine health and disease (with special reference to the role of leukotrienes in inflammatory dermatoses). PMID- 1920600 TI - A comparative study of the pharmacokinetics of thiopental in the rabbit, sheep and dog. AB - The central arterial pharmacokinetics of thiopental were studied in six rabbits, six sheep and six dogs after a short infusion at approximately 10 mg/kg min. Thiopental was infused to a defined electro-encephalographic endpoint (EEG burst suppression). The time to reach early burst suppression was longer in the dog (3.9 +/- 0.5 min) compared with the sheep (3.0 +/- 0.6 min) and the rabbit (2.5 +/- 0.5 min). The total dose required to produce the same level of EEG activity was higher in the dog (35.9 +/- 6.8 mg/kg) compared with the sheep (24.3 +/- 5.3 mg/kg) and the rabbit (21.6 +/- 6.8 mg/kg). The plasma concentration-time data for each animal was fitted using non-linear regression to a bi- or tri exponential function. In all animals, the plasma-time profile was best described as a tri-exponential decay. The initial volume of distribution was similar in all three species (rabbit, 38.6 +/- 10.0 mg/kg; sheep, 44.5 +/- 9.1 ml/kg; dog, 38.1 +/- 18.4 ml/kg). The maximum arterial plasma thiopental concentration achieved at EEG burst suppression was higher in the sheep (221.8 +/- 27.9 micrograms/ml) than the dog (164.7 +/- 29.9 micrograms/ml) or the rabbit (112.3 +/- 15.1 micrograms/ml). Thiopental distribution clearance was slower in the sheep (43.6 +/- 15.1 ml/min/kg) compared with the rabbit (110.5 +/- 18.7 ml/min kg) and the dog (97.2 +/- 47.2 ml/min kg). Elimination half-life was extended in the sheep (251.9 +/- 107.8 min) and dog (182.4 +/- 57.9 min) relative to the rabbit (43.1 +/- 3.4 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920602 TI - Disposition of human drug preparations in the horse. I. Rectally administered indomethacin. AB - A high-performance liquid chromatographic method to measure urinary indomethacin levels is described. In 0.5 ml urine, 1 micrograms/ml of indomethacin could be detected. Alkaline hydrolysis of urine resulted in the decomposition of indomethacin. When two suppositories of Indocid corresponding to 200 mg indomethacin were administered rectally to four horses the drug was rapidly absorbed and remained detectable in urine from 1 to 12 h. The excretion rate peaked after 2-3 h while the maximal concentration ranged from 18.5 to 80.6 micrograms/ml. Only 8 to 16% of the indomethacin dose was eliminated in urine after 12 h. A fraction of the dose was excreted as the glucuronide conjugate. PMID- 1920601 TI - The influence of chronic pain on the analgesic effects of the alpha 2 adrenoceptor agonist, xylazine, in sheep. AB - A comparison of the analgesic potency of the alpha 2-adrenoceptor agonist, xylazine, in control healthy sheep and sheep suffering chronic pain from footrot, indicated that the analgesic effectiveness of xylazine was significantly reduced in the animals experiencing chronic pain. This was measured by recording the threshold to a mechanically applied pressure stimulus. Furthermore, when the condition was apparently resolved, by conventional treatment over a period of 2 to 3 weeks, the decreased analgesic effectiveness of the alpha 2-agonist was still apparent although the animals were clinically cured of the footrot. PMID- 1920603 TI - An evaluation of the information given on veterinary prescriptions in Norway. Compliance with the legal regulations. AB - Compliance with Norwegian legal regulations for veterinary prescriptions was investigated and evaluated. The study was designed as a cross-sectional prescription survey, and the prescriptions were recorded in Dbase III. Of the 6505 written and telephone prescriptions collected only about one in five fulfilled the legal requirements, namely, giving information about the animal species the drug was intended for, indication for the prescribed drug and directions for use. On average 86% contained information about the animal species, while 26% and 80%, respectively, contained formation about the indication for the prescribed drug and directions for use. The number of prescriptions on which indication and directions for use were given, was significantly higher for written prescriptions than for telephone prescriptions, and for prescriptions of human preparations compared with prescriptions of veterinary preparations. For pets, the number of prescriptions containing directions for use was significantly higher than for production animals. The proportion of prescriptions for pets giving a statement of the indication was not significantly different from prescriptions for production animals. PMID- 1920604 TI - Plasma protein binding of nitroxynil in several species. AB - The binding of nitroxynil to total plasma proteins of cows, sheep and rabbits was characterized using equilibrium dialysis. The data indicate clearly that nitroxynil was highly (97-98%) bound to plasma protein of each animal. This linear binding would be due to the particular power exerted by serum albumin. The results are in good agreement with known pharmacokinetic properties of nitroxynil in domestic species. PMID- 1920605 TI - Effects of experimentally induced Pasteurella haemolytica infection in dairy calves on the pharmacokinetics of flumequine. AB - The effect of experimental Pasteurella haemolytica infection on the intravenous and intramuscular pharmacokinetics of flumequine was studied in dairy calves. The plasma concentration-time curve of flumequine after intravenous injection of 5 mg/kg bodyweight flumequine of a 10% solution before and after experimental infection, was best described by a three-compartment open model. After intramuscular injection of the same dosage rate of a 3% flumequine suspension is was best described by the one-compartment open model with first-order absorption. The experimental infection by intratracheal administration of infectious bovine rhinotracheitis (IBR)-virus and 5 days later intrapulmonary administration of Pasteurella haemolytica produced a clear temperature rise and signs of disease expressed as Average Health Status. Subsequently, plasma Fe and Zn concentration decreased after infection. The distribution volumes Vc, Vd(area) and Vd(ss) after infection (0.07 +/- 0.04, 1.38 +/- 0.36 and 0.50 +/- 0.11 l/kg, respectively) were smaller than those before infection, but the differences were not significant (P less than or equal to 0.1). The intravenous AUC infinity was significantly increased (21.86 +/- 3.51 to 33.85 +/- 2.97 mg.h/l, P less than or equal to 0.01) and the total body clearance (ClB) significantly decreased (0.24 +/- 0.02 to 0.15 +/- 0.01, P less than or equal to 0.01) after infection. After intramuscular injection of flumequine at 5 mg/kg as a 3% suspension, only the bioavailability, F, was significantly decreased after infection (78.5 +/- 14.3 to 59.7 +/- 21.2%, P less than or equal to 0.02). However, this had no consequences for the dosage regimen used. The urine concentration ratio flumequine:7-hydroxy flumequine:conjugated flumequine changed from 2:1:10 before infection to 6:1:15 after infection, which indicates that hydroxylation and glucuronidation as metabolic pathways for flumequine were decreased after Pasteurella sp. infection. PMID- 1920606 TI - Comparative in vitro susceptibility of Bacteroides and Fusobacterium isolated from footrot in sheep to 28 antimicrobial agents. AB - The agar dilution method was used to determine the bacteriostatic activity of 28 antimicrobial agents against 141 strains to the genus Bacteroides and 29 strains from the genus Fusobacterium. All organisms were isolated from clinical cases of ovine footrot. The strains were isolated from 125 Merino sheep, over a period of 2 years, from January 1987 to December 1988. The three ureidopenicillins studied (azlocillin, mezlocillin and piperacillin) proved to be the most effective antimicrobial agents. Chloramphenicol, metronidazole and tinidazole effectively inhibited the growth of Bacteroides spp., while phosphomycin was active against Fusobacterium spp. PMID- 1920608 TI - Pharmacokinetics of cephaloridine in Bubalus bubalis. PMID- 1920607 TI - Eltenac, a new anti-inflammatory and analgesic drug for horses: clinical aspects. AB - Two controlled studies to determine efficacy in the horse were performed with eltenac, a new injectable, non-steroidal anti-inflammatory drug (NSAID). Clinical trials were carried out with a dose rate of 1 mg/kg body weight in a randomized, placebo-controlled, double-blind design to assess therapeutic efficacy in acute inflammatory disorders and in animals with orthopaedic conditions. In a preliminary pharmacokinetic investigation in six horses mean elimination half life was 1.7 h after i.v. administration. In the first clinical study, analgesic activity on pain-related lameness was determined in a total of 64 horses. Pain was assessed using a rating scale. Compared with the placebo treatment, eltenac produced significant pain relief after a single i.v. injection for a period of 24 h. In the second trial the anti-oedematous effect was determined in post operative wound swelling following castration in two groups of 10 colts. After surgery, the horses received either an injection of 1 mg/kg eltenac or a placebo injection on three consecutive days. Swelling was assessed by measuring the diameter of the external preputial fold using two methods: callipers and a rating scale of 0 to 3. Additionally, photographs were taken on days 1, 2 and 4. Compared with the placebo treatment, eltenac inhibited pain and swelling significantly. The effect was maintained for up to 48 h after the last injection. PMID- 1920609 TI - Mydriasis in pigeons (Columbia livia domestica) with d-tubocurarine: topical instillation versus intracameral injection. PMID- 1920610 TI - Enantioselective N-demethylation of ketamine in the horse. PMID- 1920611 TI - Adenovirus virus-associated RNA and translation control. PMID- 1920612 TI - Regulatory sequences of duck hepatitis B virus C gene transcription. AB - The regulatory elements involved in transcription of the C gene of duck hepatitis B virus (DHBV) were investigated. Several DHBV DNA fragments were assayed for C gene promoter, enhancer, and silencer activity by using a chloramphenicol acetyltransferase (CAT) reporter gene and transfection of established liver and nonliver cell lines. A major transcript initiating at nucleotide positions 2532 and 2533 and three minor transcripts initiating at positions 2453/2454 and 2461 were identified in cells containing these constructs. These positions correspond to the 5' end of the C mRNA and were close to that of the pre-C mRNAs, respectively, found in infected livers. The pre-C mRNAs were only detected when sequences located between the initiation sites of the pre-C and C mRNAs were deleted. These sequences downregulated, in an orientation-independent fashion, a heterologous promoter and were found to contain a consensus motif common to negative transcriptional regulatory elements previously characterized in other cellular and viral genes. C gene promoter activity was only observed in highly differentiated liver cells and was dependent on a short DHBV DNA fragment containing an enhancer core consensus motif. These data indicate that transcription of the DHBV C gene is regulated by positive, negative, and differentiation factor-responsive elements. PMID- 1920613 TI - cDNA sequence and genomic characterization of intracisternal A-particle-related retroviral elements containing an envelope gene. AB - Intracisternal A-particle retrotransposons (IAPs) are retroviruslike elements that are defective in envelope protein synthesis and exist without an extracellular stage. We have isolated a novel class of cDNAs that are related to known IAP elements in the nucleotide and deduced protein sequence of gag and pol genes but also contain a previously unidentified reading frame between the pol gene and putative U3 region. Analysis of the deduced protein sequence reveals features of the putative protein that are characteristic of retroviral envelope proteins. The isolated cDNAs represent transcripts of multiple retroid elements in the mouse genome that were termed IAPE (intracisternal A-particle-related elements coding for envelope). IAPE env genes exist in approximately 200 copies per haploid genome as integral parts of the majority of these retroid elements. Four major IAPE subgroups could be distinguished after EcoRI digestion of genomic DNA. PMID- 1920614 TI - The S2 gene nucleotide sequences of prototype strains of the three reovirus serotypes: characterization of reovirus core protein sigma 2. AB - The S2 gene nucleotide sequences of prototype strains of the three reovirus serotypes were determined to gain insight into the structure and function of the S2 translation product, virion core protein sigma 2. The S2 sequences of the type 1 Lang, type 2 Jones, and type 3 Dearing strains are 1,331 nucleotides in length and contain a single large open reading frame that could encode a protein of 418 amino acids, corresponding to sigma 2. The deduced sigma 2 amino acid sequences of these strains are very conserved, being identical at 94% of the sequence positions. Predictions of sigma 2 secondary structure and hydrophobicity suggest that the protein has a two-domain structure. A larger domain is suggested to be formed from the amino-terminal three-fourths of sigma 2 sequence, which is separated from a smaller carboxy-terminal domain by a turn-rich hinge region. The carboxy-terminal domain includes sequences that are more hydrophilic than those in the rest of the protein and contains sequences which are predicted to form an alpha-helix. A region of striking similarity was found between amino acids 354 and 374 of sigma 2 and amino acids 1008 and 1031 of the beta subunit of the Escherichia coli DNA-dependent RNA polymerase. We suggest that the regions with similar sequence in sigma 2 and the beta subunit form amphipathic alpha-helices which may play a related role in the function of each protein. We have also performed experiments to further characterize the double-stranded RNA-binding activity of sigma 2 and found that the capacity to bind double-stranded RNA is a property of the sigma 2 protein of prototype strains and of the S2 mutant tsC447. PMID- 1920615 TI - Recombinational analysis of a natural noncytopathic human immunodeficiency virus type 1 (HIV-1) isolate: role of the vif gene in HIV-1 infection kinetics and cytopathicity. AB - Two molecularly cloned coisolates of human immunodeficiency virus type 1 (HIV-1) have been found to exhibit different phenotypes of viral expression, either rapid and cytopathic (N1T-A virus) or delayed and noncytopathic (N1T-E virus [X. Ma, K. Sakai, F. Sinangil, E. Golub, and D. J. Volsky, Virology 176:184-194, 1990]). To identify the viral genetic elements responsible for these phenotypes, we prepared reciprocal recombinants in different regions of N1T-A and N1T-E viral genomes. Infectivity experiments with the recombinant viruses revealed that the rapid/cytopathic (N1T-A-like) phenotype assorted cleanly with the V1f-coding region and Vif expression. The smallest HIV-1 DNA region that conferred the complete phenotypic switch was a 284-bp NdeI-StuI fragment within the vif open reading frame. Nucleotide sequence analysis revealed a 35-bp deletion starting at nucleotide 218 in the N1T-E vif gene. A 23-kDa Vif protein was detected by immunoblotting using Vif-specific antiserum in extracts of cells infected with N1T-A but not N1T-E virus. No detectable vif protein was found in association with sedimented particles of either virus. Cotransfection of a eucaryotic vif expression plasmid with N1T-E DNA complemented the N1T-E defect; rapid/cytopathic infection similar to that in N1T-A-transfected cells was observed. We conclude that Vif controls the rate, and consequently the cytopathic outcome, of HIV-1 infection. PMID- 1920616 TI - Identification of human immunodeficiency virus envelope gene sequences influencing viral entry into CD4-positive HeLa cells, T-leukemia cells, and macrophages. AB - Infectious recombinant viruses were constructed from three molecularly cloned human immunodeficiency virus (HIV) strains varying in cell tropism. All recombinants showed a high infectivity titer on phytohemagglutinin-stimulated normal T lymphocytes. However, a 120-bp region of the envelope gene including the area of the V3 hypervariable loop was found to influence infectivity titer on both clone 1022 CD4-positive HeLa cells and CD4-positive CEM leukemia cells. Infectivity for macrophages was more complex. All viruses replicated in macrophages to a low level, but viral sequences both inside and outside the V3 loop region influenced the efficiency of replication. Two experiments showed that the mechanism of restriction of infection of 1022 cells by HIV strain JR-CSF was related to lack of virus entry. First, productive virus infection occurred after transfection of 1022 cells with viral plasmid DNA. Second, the nonpermissive HIV strain JR-CSF could infect 1022 cells when pseudotyped with the envelope of other retroviruses, including human T-cell leukemia virus type I (HTLV-I), HTLV-II, and amphotropic murine leukemia virus. These results demonstrate the possibility that unexpected cell types might be infected with HIV in human patients coinfected with HIV and HTLV-I or HTLV-II. PMID- 1920617 TI - Identification of viral determinants of macrophage tropism for simian immunodeficiency virus SIVmac. AB - Simian immunodeficiency virus (SIV), a lymphocytopathic lentivirus, induces an AIDS-like disease in rhesus macaques (Macaca mulatta). A pathogenic molecular clone of rhesus macaque SIV (SIVmac), SIVmac-239, replicates and induces cytopathology in T lymphocytes but is restricted for replication in macrophages. In contrast, a nonpathogenic molecular clone of SIVmac, SIVmac-1A11, replicates and induces syncytia (multinucleated giant cells) in cultures of both T lymphocytes and macrophages. SIVmac-1A11 does not cause disease in macaques. To map the viral determinants of macrophage tropism, reciprocal recombinant genomes were constructed between molecular clones of SIVmac-239 and SIVmac-1A11. Infectious recombinant viruses were rescued by transfection of cloned viral genomes into permissive lymphoid cells. Analysis of one pair of reciprocal recombinants revealed that an internal 6.2-kb DNA fragment of SIVmac-1A11 was necessary and sufficient for both syncytium formation and efficient replication in macrophages. This region includes the coding sequences for a portion of the gag gene, all of the pol, vif, vpr, and vpx genes, the first coding exons of tat and rev, and the external env glycoprotein gp130. Thus, the transmembrane glycoprotein of env, the nef gene, the second coding exons of tat and rev, and the long terminal repeats are not essential for in vitro macrophage tropism. Analysis of additional recombinants revealed that syncytium formation, but not virus production, was controlled by a 1.4-kb viral DNA fragment in SIVmac-1A11 encoding only the external env glycoprotein gp130. Thus, gp130 env of SIVmac-1A11 is necessary for entry of virus into macrophages but is not sufficient for a complete viral replication cycle in this cell type. We therefore conclude that gp130 env and one or more genetic elements (exclusive of the long terminal repeats, transmembrane glycoprotein of env, and second coding exons of tat and rev, and nef) are essential for a complete replication cycle of SIVmac in rhesus macaque macrophages. PMID- 1920618 TI - Baculovirus gp64 gene expression: analysis of sequences modulating early transcription and transactivation by IE1. AB - Expression of the baculovirus major envelope glycoprotein gene (gp64) is regulated by transcription from both early and late promoters. To characterize the early promoter and identify sequences involved in the regulation of gp64 early transcription, promoter-reporter gene fusions were generated from the Orygia pseudotsugata nuclear polyhedrosis virus gp64 promoter and were analyzed by transient expression in uninfected insect cells. For these analyses, 5' deletion mutations were constructed in the gp64 upstream regulatory region. Larger promoter constructs were functional in uninfected Lymantria dispar cells, indicating that transcription from the gp64 early promoter required no additional viral gene products. Deletion analysis of the gp64 upstream region revealed several regulatory regions. These included a putative negative regulatory element between -319 and -166 nucleotides (nt) and multiple positive regulatory elements between -166 and -77 nt. Deletion of the TATA box located between -77 and -62 nt resulted in the loss of transcriptional activity. Cotransfections of reporter constructs and a plasmid containing a baculovirus transcriptional transactivator gene (Autographa californica nuclear polyhedrosis virus IE1) resulted in transcriptional transactivation of all constructs containing an intact TATA box. These data demonstrate that sequences upstream of the gp64 TATA box are not essential for IE1 transactivation and that only 34 nt upstream of the early transcription start site were necessary for basal levels of transcription and for transactivation by IE1. Function of the gp64 early promoter was also examined in cell lines from Spodoptera frugiperda and Drosophila melanogaster. PMID- 1920619 TI - Oligomerization, transport, and Golgi retention of Punta Toro virus glycoproteins. AB - We have investigated the oligomerization and intracellular transport of the membrane glycoproteins of Punta Toro virus, a member of the Phlebovirus genus of the family Bunyaviridae, which is assembled by budding in the Golgi complex. By using one- or two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, chemical cross-linking, and sucrose gradient centrifugation, we found that the majority of the G1 and G2 glycoproteins are assembled into noncovalently linked G1-G2 heterodimers. At the same time, a fraction of the G2 protein, possibly produced independently of the G1 protein, is assembled into G2 homodimers. Kinetic analysis indicates that heterodimerization occurs between newly synthesized G1 and G2 within 3 min after protein synthesis, and that the G1 and G2 glycoproteins are associated as dimeric forms both during transport and after accumulation in the Golgi complex. Analysis of a G1-truncated G2 mutant, which is also targeted to the Golgi complex, showed that these molecules also assemble into dimeric forms, which are linked by disulfide bonds. Both the G1-G2 heterodimer and the G2 homodimer were found to be able to exit from the endoplasmic reticulum. Differences in transport kinetics observed for the G1 and G2 proteins may be due to the differences in the transport efficiency between the G1-G2 heterodimer and the G2 homodimer from the endoplasmic reticulum to the Golgi complex. These and previous results (S.-Y. Chen, Y. Matsuoka, and R.W. Compans, Virology 183:351-365, 1991) suggest that Golgi retention of the G2 homodimer occurs by association with the G1-G2 heterodimer, whereas the Golgi targeting of the G1-G2 heterodimer occurs by a specific retention mechanism. PMID- 1920620 TI - Extracellular vaccinia virus formation and cell-to-cell virus transmission are prevented by deletion of the gene encoding the 37,000-Dalton outer envelope protein. AB - There are two types of infectious vaccinia virus particles: intracellular naked virions and extracellular enveloped virions (EEV). To determine the biological role of the enveloped form of vaccinia virus, we produced and characterized a mutant that is defective in EEV formation. The strategy involved replacement by homologous recombination of the gene F13L, encoding a 37,000-Da protein (VP37) that is specific for the outer envelope of EEV, with a selectable antibiotic resistance marker, the Escherichia coli gpt gene. Initial experiments, however, suggested that such a mutation was lethal or prevented plaque formation. By employing a protocol consisting of high-multiplicity passages of intracellular virus from the transfected cells and then limiting dilution cloning, we succeeded in isolating the desired mutant, which was defective in production of plaques and extracellular virus but made normal amounts of intracellular naked virions. Electron microscopic examination indicated that the mutant virus particles, unlike wild type, were neither wrapped with Golgi-derived membranes nor associated with the cell surface. The absence of VP37 did not prevent the transport of the viral hemagglutinin to the plasma membrane but nevertheless abrogated both low-pH- and antibody-mediated cell fusion. These results indicate that VP37 is required for EEV formation and also plays a critical role in the local cell-to-cell transmission of vaccinia virus, perhaps via enveloped virions attached to or released from the cell membrane. By contrast, a mutated virus with a deletion of the K4L open reading frame, which is a homolog of the VP37 gene, was not defective in formation of plaques or EEV. PMID- 1920621 TI - Inhibition of human immunodeficiency virus replication in acutely infected CD4+ cells by CD8+ cells involves a noncytotoxic mechanism. AB - The mechanism by which CD8+ T cells from human immunodeficiency virus (HIV) infected individuals suppress HIV replication in acutely infected CD4+ T cells was investigated. Cytotoxicity was not involved, as the antiviral activity of the CD8+ cells did not correlate with the ability to lyse HIV-infected or uninfected CD4+ T cells. In addition, the frequency of HIV-infected CD4+ cells increased during coculture with CD8+ T cells even in the absence of detectable levels of virus replication. Moreover, separation of the CD4+ and CD8+ cells by a 0.4 micron-pore-size filter delayed HIV replication, indicating a role, at least in part, for a soluble factor. However, cell contact was required for optimal antiviral activity. These results extend further the observation on the mechanism of antiviral HIV activity by CD8+ cells from infected individuals. They support the conclusion that CD8+ cells can play a major role in preventing development of disease in HIV-infected individuals. PMID- 1920622 TI - Specific binding of host cell proteins to the 3'-terminal stem-loop structure of rubella virus negative-strand RNA. AB - At the 5' end of the rubella virus genomic RNA, there are sequences that can form a potentially stable stem-loop (SL) structure. The complementary negative-strand equivalent of the 5'-end SL structure of positive-strand rubella virus RNA [5' (+) SL structure] is thought to serve as a promoter for the initiation of positive-strand synthesis. We screened the negative-strand equivalent of the 5' (+) SL structure (64 nucleotides) and the adjacent region of the negative-strand RNA for their ability to bind to host cell proteins. Specific binding to the 64 nucleotide-long potential SL structure of three cytosolic proteins with relative molecular masses of 97, 79, and 56 kDa was observed by UV-induced covalent cross linking. There was a significant increase in the binding of the 97-kDa protein from cells upon infection with rubella virus. Altering the SL structure by deleting sequences in either one of the two potential loops abolished the binding interaction. The 56-kDa protein also appeared to bind specifically to an SL derived from the 3' end of positive-strand RNA. The 3'-terminal structure of rubella virus negative-strand RNA shared the same protein-binding activity with similar structures in alphaviruses, such as Sindbis virus and eastern equine encephalitis virus. A possible role for the host proteins in the replication of rubella virus and alphaviruses is discussed. PMID- 1920623 TI - Effector domains of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex are functionally interchangeable and share an essential peptide motif. AB - The human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex transactivators are posttranscriptional regulatory proteins that promote retroviral gene expression by interacting with specific viral mRNAs. Rev and Rex have markedly dissimilar amino acid sequences and RNA target specificities but are thought to act through the same cellular pathway. In this report, we demonstrate that short peptide domains which are required for effector activity in Rev and Rex are functionally interchangeable. Activity of these effector domains depends upon a previously unrecognized tetrapeptide motif that is present in both Rev and Rex and also in analogous proteins from other complex retroviruses. The conserved effector motif may mediate essential interactions of Rev, Rex, and other transactivators of this type with a common cellular cofactor. PMID- 1920624 TI - Anti-glycoprotein D monoclonal antibody protects against herpes simplex virus type 1-induced diseases in mice functionally depleted of selected T-cell subsets or asialo GM1+ cells. AB - Passive transfer of a monoclonal antibody (MAb) specific for glycoprotein D (gD) is highly effective in preventing the development of herpes simplex virus type 1 induced stromal keratitis. In the present study, we investigated whether animals which had been functionally depleted of T-cell subsets or asialo GM1+ cells would continue to be responsive to MAb therapy. BALB/c mice were depleted of CD4+, CD8+, or asialo GM1+ cells by treatment with anti-L3T4, anti-Lyt 2.2, or anti asialo GM1 antibodies, respectively. Functional depletion of CD4+ cells was documented by the loss of delayed-type hypersensitivity responsiveness, while CD8+ cell depletion was accompanied by abrogation of cytotoxic lymphocyte activity. Anti-asialo GM1 treatment led to the loss of natural killer cell lytic activity. Mice depleted of the desired cell population and infected on the scarified cornea with herpes simplex virus type 1 uniformly developed necrotizing stromal keratitis by 3 weeks postinfection. A single inoculation of anti-gD MAb (55 micrograms) given intraperitoneally 24 h postinfection strongly protected hosts depleted of CD4+ cells against stromal keratitis. Likewise, antibody treatment in CD8+ or asialo GM1+ cell-depleted hosts was as therapeutically effective as that seen in non-cell-depleted mice. We also observed that in cell depleted mice, the virus spread into the central nervous system and caused encephalitis. The CD4+ cell-depleted mice were the most severely affected, as 100% developed fatal disease. Anti-gD MAb treatment successfully protected all (32 of 32) CD4+-, CD8+-, or asialo GM1(+)-depleted hosts against encephalitis. We therefore conclude that antibody-mediated prevention of stromal keratitis and encephalitis does not require the obligatory participation of CD4+, CD8+, or asialo GM1+ cells. However, when mice were simultaneously depleted of both CD4+ and CD8+ T-cell subsets, antibody treatment could not prevent fatal encephalitis. Thus, antibody can compensate for the functional loss of one but not two T lymphocyte subpopulations. PMID- 1920625 TI - Infectious entry pathway of adenovirus type 2. AB - Internalization of the infectious fraction of human adenovirus type 2 into HeLa cells was followed by a quantitative internalization assay. Treatments known to selectively block receptor-mediated endocytosis reduced the internalization of infectious virus to an extent close to the reduction of endocytosis of transferrin. This suggests that one of the first steps in the infectious cycle of adenovirus type 2 is internalization by the coated-pit and -vesicle pathway. PMID- 1920626 TI - Activity of CD4+ T-cell clones of type 1 and type 2 in generation of influenza virus-specific cytotoxic responses in vitro. AB - The activity of distinct CD4+ T-helper cell (Th) clones in promoting secondary A/PR/8/34/Mt.S.(H1N1) (A/PR8) influenza virus-specific, class I-restricted cytotoxic T-lymphocyte (CTL) responses in vitro was examined. CD8+ T cells which had been purified by fluorescence-activated cell sorter from spleen cells of A/PR8-primed mice were used as responders. On their own, purified CD8+ T cells were unable to generate cytotoxic activity upon in vitro culture with A/PR8 infected stimulator cells. Significant cytotoxic activity was generated in cultures that were additionally supplemented with A/PR8-specific Th clones or cell-free supernatant from these clones. Although there were large differences among individual Th clones in this function, Th clones of type 1 (Th1) promoted, on average, significantly stronger cytotoxic responses than Th clones of type 2 (Th2). The differences in promotion of a cytotoxic response correlated with the amount of interleukin-2 (IL-2) or IL-4 secreted by individual Th clones. These two lymphokines accounted for the CTL-promoting activity of the respective Th clones, since addition of recombinant IL-2 (IL-2) or rIL-4 to Th-free cultures substituted fully for the respective Th clones. As observed with Th clones, rIL-2 was significantly more effective than rIL-4 in promoting a cytotoxic response. When used in combination, Th2 clones had an antagonistic effect on the generation of a CTL response by Th1 clones. This effect could be partially transferred with cell-free supernatant from activated Th2 clones and could be reversed by addition of excess rIL-2. Both consumption of IL-2 by Th2 and secretion of an inhibitory factor(s) appear to be involved in this phenomenon. PMID- 1920627 TI - Persistent human immunodeficiency virus type 1 infection in human fetal glial cells reactivated by T-cell factor(s) or by the cytokines tumor necrosis factor alpha and interleukin-1 beta. AB - Human immunodeficiency virus type 1 (HIV-1) infection of the brain has been associated with a severe dementing illness in children and adults. However, HIV-1 antigens are most frequently found in macrophages and microglial cells. To determine the extent of susceptibility of neuroglial cells to infection, the HIV 1 genome was introduced into cells cultured from human fetal brain tissue. Astroglial cells rapidly transcribed the viral genome producing high levels of p24 protein and infectious virions which peaked two to three days posttransfection. Thereafter HIV-1 genome expression progressively diminished and a persistent phase of infection developed during which neither virus nor viral proteins could be demonstrated by immunodetection methods. Cocultivation with CD4+ T cells at any time during the persistent infection resulted in resumption of p24 synthesis and virus multiplication. The release of persistence did not require direct cell-cell contact between the glial and T cells, since separation of the two cell types across a permeable membrane resulted in a delayed but similar resumption of p24 synthesis and virus multiplication. The persistently infected glial cells could also be stimulated to produce viral p24 protein if either tumor necrosis factor alpha or interleukin-1 beta was added to the medium without T cells present. These results suggest that astrocytes may serve as an undetected reservoir for HIV-1 and disseminate the virus to other susceptible cells in the brain upon triggering by some cellular or biochemical signal. PMID- 1920628 TI - Vaccinia virus morphogenesis is interrupted when expression of the gene encoding an 11-kilodalton phosphorylated protein is prevented by the Escherichia coli lac repressor. AB - A conditional lethal vaccinia virus mutant, which constitutively expresses the Escherichia coli lac repressor and has the lac operator controlling the F18R gene (the 18th open reading frame of the HindIII F fragment of the vaccinia virus strain WR genome) encoding an 11-kDa protein, was previously shown to be dependent on the inducer isopropyl-beta-D-thiogalactoside (IPTG) for replication (Y. Zhang and B. Moss, Proc. Natl. Acad. Sci. USA 88:1511-1515, 1991). Further studies indicated that the yield of infectious virus could be regulated by titration with IPTG and that virus production was arrested by IPTG removal at appropriate times. Under nonpermissive conditions, an 11-kDa protein reactive with antiserum raised to a previously described DNA-binding phosphoprotein (S. Y. Kao and W. R. Bauer, Virology 159:399-407, 1987) was not synthesized, indicating that the latter is the product of the F18R gene. In the absence of IPTG, replication of viral DNA and the subsequent resolution of concatemeric DNA molecules appeared normal. Omission of IPTG did not alter the kinetics of early and late viral protein synthesis, although the absence of the 11-kDa polypeptide was noted by labeling infected cells with [35S]methionine or [32P]phosphate. Pulse-chase experiments revealed that proteolytic processing of the major viral structural proteins, P4a and P4b, was inhibited under nonpermissive conditions, suggesting a block in virus maturation. Without addition of IPTG, the failure of virus particle formation was indicated by sucrose gradient centrifugation of infected cell lysates and by the absence of vaccinia virus-mediated pH-dependent cell fusion. Electron microscopic examination of infected cells revealed that immature virus particles, with aberrant internal structures, accumulated when synthesis of the 11-kDa DNA-binding protein was prevented. PMID- 1920629 TI - Borna disease: association with a maturation defect in the cellular immune response. AB - Borna disease virus (BDV) is a negative-strand RNA virus which produces persistent infection in a variety of experimental animals. In the rat, the presence or absence of clinical signs of Borna disease, a characteristic, biphasic neurobehavioral illness, depends on host-related factors. A window of opportunity exists after birth wherein inoculation with BDV produces a persistently infected rat without signs of Borna disease or encephalitis (persistent, tolerant infection-newborn [PTI-NB] rat). Although immunopathological destruction of the nervous system does not occur in the PTI-NB rat, significant alterations in the development of the nervous system were noted, including site-specific lysis of neurons. Unlike the case with other pharmacologically produced, persistent, tolerant BDV infections, adoptive transfer of spleen cells from BDV-infected rats did not produce disease in the PTI-NB rats. PTI-NB rats developed Borna disease after being connected by parabiosis to rats with Borna disease. Bone marrow transplantation experiments revealed that bone marrow cells from PTI-NB rats produced Borna disease in lethally irradiated, BDV-infected recipient rats. Bone marrow from PTI-NB rats contained a complement of inflammatory cells capable of inducing Borna disease. Thus, the loss of BDV-specific cellular immunity appeared to occur after the release of cells from the bone marrow. PMID- 1920630 TI - The S protein of bovine coronavirus is a hemagglutinin recognizing 9-O-acetylated sialic acid as a receptor determinant. AB - The S protein of bovine coronavirus (BCV) has been isolated from the viral membrane and purified by gradient centrifugation. Purified S protein was identified as a viral hemagglutinin. Inactivation of the cellular receptors by sialate 9-O-acetylesterase and generation of receptors by sialylation of erythrocytes with N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) indicate that S protein recognizes 9-O-acetylated sialic acid as a receptor determinant as has been shown previously for intact virions. The second glycoprotein of BCV, HE, which has been thought previously to be responsible for the hemagglutinating activity of BCV, is a less efficient hemagglutinin; it agglutinates mouse and rat erythrocytes, but in contrast to S protein, it is unable to agglutinate chicken erythrocytes, which contain a lower level of Neu5,9Ac2 on their surface. S protein is proposed to be responsible for the primary attachment of virus to cell surface. S protein is proposed to be responsible for the primary attachement of virus to cell surface receptors. The potential of S protein as a probe for the detection of Neu5,9Ac2-containing glycoconjugates is demonstrated. PMID- 1920631 TI - Macrophages are the first thymic cells to express polytropic retrovirus in AKR mouse leukemogenesis. AB - AKR mice spontaneously develop T-cell leukemias in the thymus late in the first year of life. These neoplasms arise following the appearance in the thymus of a recombinant retrovirus but can be prevented by thymectomy, indicating a role for both virus and elements of the thymic microenvironment in leukemogenesis. The intrathymic appearance of recombinant retrovirus was examined at ages leading up to leukemogenesis in order to identify and characterize the microenvironments in which the virus is first expressed. A stromal cell, the macrophage, was found to be the first thymic element to produce detectable levels of recombinant retrovirus, approximately 12 weeks before thymocytes. This observation provides a mechanism to reconcile viral leukemogenesis with the requirement for an intact thymus. Thus, a nonlymphoid cell, the macrophage, may play a critical role in the development of lymphoid neoplasia. PMID- 1920632 TI - Discontinuous sequence change of human immunodeficiency virus (HIV) type 1 env sequences in plasma viral and lymphocyte-associated proviral populations in vivo: implications for models of HIV pathogenesis. AB - Sequence change in different hypervariable regions of the external membrane glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1) was studied. Viral RNA associated with cell-free virus particles circulating in plasma and proviral DNA present in HIV-infected peripheral blood mononuclear cells (PBMCs) were extracted from blood samples of two currently asymptomatic hemophiliac patients over a 5-year period. HIV sequences were amplified by polymerase chain reaction to allow analysis in the V3, V4, and V5 hypervariable regions of gp120. Rapid sequence change, consisting of regular replacements by a succession of distinct viral populations, was found in both plasma virus and PBMC provirus populations. Significant differences between the frequencies of sequence variants in DNA and RNA populations within the same sample were observed, indicating that at any one time point, the predominant plasma virus variants were antigenically distinct from viruses encoded by HIV DNA sequences in PBMCs. How these findings contribute to current models of HIV pathogenesis is discussed. PMID- 1920633 TI - Assembly of nucleocapsidlike structures in animal cells infected with a vaccinia virus recombinant encoding the measles virus nucleoprotein. AB - A vaccinia virus recombinant containing the measles virus nucleoprotein gene was shown to induce the synthesis of a 60 kDa phosphorylated nucleoprotein similar to authentic measles virus nucleoprotein. Mammalian or avian cells infected with the recombinant virus displayed tubular structures reminiscent of viral nucleocapsids both in the cytoplasm and in the nucleus. Such structures could be labelled in situ by using an immunogold detection method specific for measles virus proteins. Electron microscopic examination of tubular structures purified from cells infected with the vaccinia virus recombinant indicated that they displayed most of the features of measles virus nucleocapsids, although their length was on the average shorter. These results demonstrate the spontaneous assembly of measles virus nucleocapsids in the absence of viral leader RNA and provide a means for a detailed molecular analysis of the requirements for nucleocapsid assembly. Furthermore, these findings raise the possibility of achieving complete assembly of measles virus particles, devoid of infectious RNA, by using a vaccinia virus vector. PMID- 1920634 TI - Inhibition of human immunodeficiency virus type 1-induced cell fusion by recombinant human interferons. AB - Pretreatment of HeLa T4 cells with recombinant alpha, beta, or gamma interferon (IFN) was found to significantly inhibit syncytium formation induced by the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein. All three IFNs were found to be potent inhibitors of fusion in a system in which Spodoptera frugiperda cells, infected with a baculovirus recombinant expressing the HIV-1 envelope protein, were cocultivated with HeLa T4 cells. In addition, these IFNs were also found to block HeLa T4 cell fusion induced by the HIV-1 envelope proteins expressed from a vaccinia virus recombinant. Furthermore, the IFNs inhibited cell fusion between HIV-1 envelope glycoprotein-expressing cells and either immortalized or fresh CD4+ lymphocytes pretreated with the IFNs. These results suggest that further testing of human IFNs for therapy of HIV-1 infection will be of interest. PMID- 1920635 TI - The 5' end of coronavirus minus-strand RNAs contains a short poly(U) tract. AB - A radiolabeled oligodeoxynucleotide primer that anneals near the common 5' end of bovine coronavirus minus-strand RNAs was extended with reverse transcriptase, and a major product suggesting poly(U) tracts of 8 to 20 nucleotides was found. The extended primer molecules were ligated head to tail, amplified by the polymerase chain reaction, cloned, and sequenced, and poly(U) tracts of 9 to 26 nucleotides were found. Poly(A) tails of 100 to 130 nucleotides on the 3' end of coronavirus plus-strand mRNAs and genome must, therefore, be generated by a mechanism that uses only a short poly(U) template. This pattern contrasts with that of other cytoplasmic, polyadenylated, plus-strand animal RNA viruses which utilize a full length poly(U) template for poly(A) synthesis. PMID- 1920636 TI - A novel cis-acting element that controls transcription of human immunodeficiency virus type 1 DNA, depending on cell type. AB - cis-acting elements for the transcription of human immunodeficiency virus type 1 DNA were analyzed in cell-free transcription and DNA transfection assays. Besides previously identified cis elements, a region adjacent to the enhancer element was found to regulate transcription in both assays. Loss of this region caused 4.3- and 1.6-fold transcription inhibition in a transfection assay with a T-cell line, MOLT-4, and a monocyte line, U937, respectively, whereas the same region appeared to function negatively with other T-cell lines, MT-4 and Jurkat. These results suggest that this novel cis element regulates the transcription of proviral DNA in a cell-type-specific manner. PMID- 1920637 TI - Use of recombinant retroviruses to characterize the activity of antiretroviral compounds. AB - This report describes the use of a recombinant murine retrovirus encoding beta galactosidase (PLJ beta-gal retrovirus) to study the antiretroviral activity of zidovudine (AZT) and other nucleoside analogs. The PLJ beta-gal virus permits the rapid and unequivocal identification of individual virus-infected cells arising from a single cycle of viral replication. With this model system, AZT is shown to completely and irreversibly prevent retrovirus infection of proliferating cell lines as measured by a lack of reporter gene expression. On the other hand, AZT is less effective in protecting growth-arrested cells from retroviral infection. Recombinant retroviruses such as the PLJ beta-gal virus are potentially useful reagents for the identification and characterization of antiretroviral compounds. PMID- 1920638 TI - Identification of a retinoic acid-inducible endogenous retroviral transcript in the human teratocarcinoma-derived cell line PA-1. AB - Retinoic acid (RA), a developmental morphogen, causes activation of a transcript of an endogenous retrovirus-related element in the human teratocarcinoma-derived cell line PA-1. This provirus is defective, and the provirus-related sequences exist as multicopy elements (more than 20 copies) in human DNA. This is the first human endogenous retroviral mRNA that is known to be transcriptionally activated by RA. The nucleotide sequence of the 3,357 bp of this viral cDNA was determined and shows a strong homology to the type C-related human endogenous retroviral proviruses ERV3 and 4-1. This cDNA contains 'R-U5-delta pol-env-U3-R sequences of the provirus. Adjacent to the putative 5' long terminal repeat of this provirus there is an 18-bp sequence complementary to the 3' end of isoleucine tRNA. We named this RA-responsive virus RRHERV-I. PMID- 1920639 TI - Induction of alpha interferon by human immunodeficiency virus type 1 in human monocyte-macrophage cultures. AB - The induction of interferon (IFN) by human immunodeficiency virus type 1 (HIV-1) in primary, nonstimulated monocyte-macrophage cultures was studied. HIV-1 infection, as confirmed by p24 antigen levels in the cell supernatant, led to the production of alpha interferon (IFN-alpha) over 7 to 21 days following infection. In two of seven experiments, the IFN detected was acid labile. Coupled reverse transcription-polymerase chain reaction analysis confirmed the induction of IFN alpha mRNA in cells of HIV-1-infected cultures. PMID- 1920641 TI - Factors affecting the patency of small-caliber prostheses: Observations in a suitable canine model. AB - Lack of an endothelial surface is most often blamed for the relatively poor patency of polytetrafluoroethylene grafts used in infrageniculate bypass when compared to autogenous saphenous vein. Length, caliber, flow, and ability to withstand flexion are also acknowledged but have not been systematically examined. We report the results of our attempts to discriminate between the relative contributions of these factors and to develop a suitable canine model for evaluating small-caliber prostheses (4 mm x 10 cm thin-walled polytetrafluoroethylene). ASA/dipyridamole were given 1 week before and 4 weeks after operation. Patency was assessed by directional Doppler at frequent intervals (less than or equal to 3 days). The following were observed: (1) Iliac placement provided a useful patency reference point (40% to 50% patency at 60 days). (2) Carotid patency was not better than iliac patency. (3) Crossing a flexion crease decreased patency. (4) The low patencies were not technical but intrinsic to the graft. Iliofemoral vein grafts achieved 100% patency at 60 days. (5) External rings did not improve iliofemoral patency (equal in paired comparisons). (6) Neither baseline platelet aggregation nor platelet aggregation after ASA administration correlated with patency. This canine model is an excellent test for small caliber-low flow prostheses. It allows paired-site comparisons, which are essential, and meaningful patency data with reasonable numbers of subjects within 2 months' observation. Directional Doppler evaluation avoids need for angiography or serial postmortem analysis sacrifice. PMID- 1920642 TI - Initial evaluation of absorbable polydioxanone suture for peripheral vascular surgery. AB - The long-term integrity of an autogenous vascular anastomosis is primarily dependent on the strength of tissue healing; therefore permanent mechanical support of an autogenous anastomosis with sutures is unnecessary. In this study we evaluated monofilament absorbable polydioxanone as an alternative to polypropylene for suturing autogenous vascular tissue during adult peripheral vascular operations. We used polydioxanone suture for 21 vascular procedures in 20 patients. We evaluated suture handling characteristics during operation and then followed patients with clinical assessments and serial duplex scans to monitor for pseudoaneurysms, anastomotic narrowing, and vessel patency. Indications for surgery included limb salvage (67%), dialysis access (23%), traumatic arteriovenous fistula and claudication (5% each). The operative procedures included infrainguinal bypass (57%), arteriovenous fistula formation (24%), thromboembolectomy (14%), and arteriovenous fistula repair (5%). Polydioxanone sutures were placed in 39 separate test sites (35 arterial, 4 venous). No deaths occurred during operation. Polydioxanone suture was found to have handling characteristics similar to polypropylene. During mean patient follow-up of 7.2 +/- 0.6 months, we found no cases of anastomotic narrowing or pseudoaneurysms. Actuarial test site patency at 1, 3, and 6 months was 97%, 97%, and 86%, respectively. Polydioxanone suture has handling properties that are acceptable for use in vascular applications, and it provides adequate mechanical support for sutured vessels to heal. A randomized trial comparing polydioxanone with polypropylene suture will be necessary to determine whether the lack of permanent foreign material in vascular anastomoses can improve long-term patency. PMID- 1920640 TI - Analysis of Moloney murine leukemia virus revertants mutated at the gag-pol junction. AB - Among Moloney murine leukemia viruses (Mo-MuLVs) having stop codons other than UAG at the gag-pol junction, Mo-MuLV with UAA, but not with UGA, had a replication disadvantage. Mo-MuLV with a glutamine codon (CAG) at the junction did not replicate. A revertant of this virus consisted of the original virus and a virus with a deletion of the pol region. Protease and Pr65gag encoded by their respective genomes complemented each other. PMID- 1920643 TI - Abdominal aortic aneurysm in the patient undergoing cardiac transplantation. AB - In the past 3 years at our institution 130 patients have undergone cardiac transplantation for ischemic cardiomyopathy in 49 (38%), idiopathic cardiomyopathy in 42 (32%), viral cardiomyopathy in 9 (6.9%), pulmonary hypertension in 8 (6%), and graft atherosclerosis in 2 (1.5%). Routine preoperative abdominal ultrasonography was performed on 98 (75%) of these patients with specific visualization of the abdominal aorta in 93 (95%). Abdominal aortic aneurysms (all infrarenal) were found before operation in four patients and only in the subgroup undergoing transplantation for ischemic heart disease (10.5%). They measured 3.4, 4.5, 3.6, and 3.8 cm before transplantation. Periodic evaluation by ultrasonography was carried out after transplantation during the 3-year period of this study. One aneurysm that was initially 3.6 cm increased to 4.0 cm and ruptured 2 months after transplantation. The patient died despite emergent surgery. Aneurysms in three patients who demonstrated rapid aneurysm expansion after transplantation were successfully repaired at 5, 20, and 33 months after transplantation when the lesions reached 5.5, 5.9, and 4.8 cm. A fifth patient with an initially normal (1.5 cm) aorta developed a symptomatic aneurysm of 4.1 cm, which was repaired uneventfully. The average expansion rate of these aneurysms after transplantation was 0.74 +/- 0.15 cm/year. This experience suggests that aneurysms are limited to patients undergoing transplantation for ischemic heart disease. Ultrasound examination may be appropriate for preoperative screening. Careful aortic surveillance after transplantation is important in patients having transplantation for ischemic cardiomyopathy because of the apparent rapid expansion rate compared to aneurysms in the population not receiving transplants. PMID- 1920644 TI - The role of arterial reconstruction in spontaneous renal artery dissection. AB - Spontaneous renal artery dissection is an uncommon cause of renovascular hypertension, usually associated with fibromuscular dysplasia. Among reported nonautopsy cases (N = 80), arterial reconstruction has seldom been attempted (N = 21) and the outcome has frequently been poor (48% clinical failure rate). This is attributed in part to the frequent involvement of renal artery branches by the dissection. Furthermore, the report of spontaneous reversion to normotension among patients treated medically has also clouded the role of surgery in this disease. Since progress in the technique of renal artery repair now allows successful treatment of anatomically complex lesions, we reviewed our experience with arterial reconstruction in the management of spontaneous renal artery dissection to determine the frequency of and factors correlating with cure after operative repair. Ten patients (eight men, two women; mean age, 39.3 +/- 5.9 years) were admitted with severe hypertension (10/10), often associated with neurologic symptoms, hematuria, or flank pain (8/10). Serum creatinine was elevated in only two patients. Angiography demonstrated changes consistent with fibromuscular dysplasia in 7 of 10 patients and evidence of dissection in 6 of 10. Bilateral disease was present in three patients. Only five patients had a single renal artery on the involved side. The dissection extended into the primary branches in 8 of 10 patients and involved both renal arteries in four of the five patients with two arteries. Histologic study confirmed fibromuscular dysplasia in six and intramural dissection in all operative specimens. Five patients underwent revascularization (in one case requiring the ex vivo technique), with use of hypogastric artery as a conduit in four of five or resection and primary reanastomosis in one of five. Three patients became normotensive, and two returned to their previous level of blood pressure control. Follow-up averaged 14.5 years. Two patients underwent nephrectomy after exploration demonstrated nonreconstructible vessels, and two underwent nephrectomy when intraoperative assessment of the kidney showed that revascularization had failed to adequately reverse extensive renal ischemia. After a mean follow-up of 14.6 years these patients remain normotensive, although two require antihypertensive medications. One patient was treated medically and is currently hypertensive off all medications. Nine of 10 patients have maintained a normal serum creatinine during follow-up. We conclude that renal revascularization is frequently successful in spontaneous renal artery dissection (five of seven, 71.4%) and results in sustained relief of hypertension with maximal conservation of renal tissue. This is important because of the young age at onset and the not infrequent occurrence of bilateral fibromuscular dysplasia, and even of dissection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1920645 TI - Septic embolism complicating infective endocarditis. AB - Embolic phenomena in patients with infective endocarditis may complicate the placement of a cardiac valvular prosthesis. To evaluate the vascular consequences of these emboli, a 15-year review of 102 patients undergoing valve replacement for proven infective endocarditis was undertaken. Thirty-one patients with 36 episodes of septic embolization were identified. Ten of these were separate extremity occlusive events. All patients with extremity emboli were admitted with pain; four had limb-threatening emboli. All patients grew gram-positive bacteria from their blood except a single Candida albicans isolate. Appropriate antimicrobial therapy was used in all patients. Angiography confirmed the diagnosis in 11 of 12 patients. Embolic targets included the lower extremities in all except a single instance. Four patients had multiple emboli. All but one of the vascular procedures were carried out subsequent to or simultaneously with cardiac valve replacement. Initial operative management included embolectomy (4) and primary amputation (2). Two delayed procedures were required. One patient died. Four patients had limited ischemia that resolved with antibiotics and anticoagulation. This report suggests that infective endocarditis requiring valvular replacement is associated with embolization in one third of patients. The presentation of peripheral vascular emboli is that of acute extremity ischemia. The diagnosis should be confirmed by angiography to rule out the possibility of multiple emboli. When possible, valve replacement should precede peripheral vascular management, which may include operative or medical components as dictated by the extent of limb ischemia. PMID- 1920646 TI - Reflex sympathetic dystrophy--the surgeon's role in management. AB - It is important for vascular surgeons to be familiar with reflex sympathetic dystrophy because they may be called on to participate in the evaluation and treatment of patients with this syndrome. Over a 3 1/2-year period, 35 patients, initially evaluated by a team of pain experts, were referred for surgical sympathectomy for reflex sympathetic dystrophy. All patients had at least one positive diagnostic sympathetic block before they were considered for surgical sympathectomy. With use of this team approach and careful patient selection, excellent results were obtained in 74%, good results in 17%, and poor results in 9%. Three patients required a repeat cervical sympathectomy after initial surgery failed to relieve their symptoms. One patient required a contralateral lumbar sympathectomy after ipsilateral sympathectomy was unsuccessful. Better results were obtained in patients treated earlier in their course and with extended surgical sympathectomy. Patients not responding to initial sympathectomy should be evaluated for the presence of residual functional sympathetic tissue, and if this is identified, further sympathectomy by an alternate approach appears justified. PMID- 1920647 TI - In vivo human comparison of intravascular ultrasonography and angiography. AB - This study evaluates the in vivo correlation of intravascular ultrasonography and uniplanar angiography in determining the luminal dimensions of normal and moderately atherosclerotic human arteries. Five French and 8F rotating A scan intravascular ultrasound catheters were used to obtain 48 images in four superficial femoral arteries, five iliac arteries, and one aorta in eight patients undergoing vascular surgery. Cross-sectional areas measured by intravascular ultrasonography were compared to cross-sectional areas calculated by uniplanar angiography of the same location in the vessel. Maximum and minimum luminal diameters were also measured from intravascular ultrasound images. An ellipticity index was defined as the maximum/minimum diameter ratio (max/min) and ranged from 1.0 to 1.8 (mean, 1.2). Comparison of the cross-sectional areas measured from intravascular ultrasound images and those calculated from uniplanar angiography showed no significant difference at any level of ellipticity studied. However, when the values of cross-sectional areas were analyzed in groups corresponding to the diameter of the vessel, that is, aortic, iliac, and femoral, the values for the iliac arteries calculated from uniplanar angiography were significantly greater by 9.8% +/- 0.7% (n = 29, p = 0.03) when compared to those measured by intravascular ultrasonography. In addition to providing accurate luminal determinations, intravascular ultrasound images displayed transmural morphology, the location and character of the atherosclerotic lesions, and the thickness of the vessel wall. We conclude that intravascular ultrasound imaging provides accurate, novel information regarding human vessels and that this technology may play a significant role in future diagnostic and interventional therapies. PMID- 1920648 TI - Real-time color duplex scanning after sclerotherapy of the greater saphenous vein. AB - A color real-time duplex scanner was used to scan the greater saphenous vein in 89 limbs of 55 patients to study the efficacy of prior greater saphenous vein sclerotherapy. The greater saphenous vein was insonated from the saphenofemoral junction to the knee to evaluate both reflux to a standardized 30 mm Hg Valsalva maneuver and evidence of greater saphenous vein obliteration by sclerotherapy. These data were correlated with the number of sclerosing injections used (mean, 1.8; range, 1 to 6), time from the last injection (mean, 27.5 mo.; range, 3 to 55 mo), and concentration of injectant used (0.5% to 3% sodium tetradecyl sulfate). Fifty-one of 89 injected limbs (57%) demonstrated reflux through the saphenofemoral junction, and reflux down the more distal greater saphenous vein was found in 67 of 89 injected limbs (75%). Greater saphenous vein obliteration was noted in only 18 of 89 injected limbs (20%); two were totally obliterated, and 16 were partially obliterated. The greater saphenous vein was obliterated in 6% below a refluxing saphenofemoral junction and in 40% below a nonrefluxing junction. A greater saphenous vein obliteration rate of 9% was found with a refluxing greater saphenous vein, and 50% in a nonrefluxing greater saphenous vein. Femoral vein reflux was identified in 11 of the 110 limbs (10%) and in every case was associated with both saphenofemoral junction and greater saphenous vein reflux. We noted a trend toward more successful results with more concentrated injectate (3% sodium tetradecyl sulfate). Fifty percent of patients reported improvement in symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920649 TI - Duplex ultrasound criteria for diagnosis of splanchnic artery stenosis or occlusion. AB - Mesenteric artery duplex scanning appears promising for detection of splanchnic artery stenosis or occlusion or both in patients with symptoms suggestive of chronic intestinal ischemia. However, no specific duplex criteria have been developed for detection of mesenteric artery stenosis. We obtained mesenteric artery duplex scans and infradiaphragmatic lateral aortograms in 34 patients to determine duplex criteria for mesenteric stenosis. Seventy percent or greater angiographic stenosis was present in 10 superior mesenteric arteries and 16 celiac arteries. Duplex scans were reviewed to determine if celiac artery and superior mesenteric artery ratios of peak systolic velocities and end-diastolic velocities to peak aortic systolic velocity, as well as celiac artery and superior mesenteric artery peak systolic velocities and end-diastolic velocities alone, could predict a greater than or equal to 70% angiographic stenosis or occlusion or both. The results obtained by use of receiver operator curves indicated peak systolic velocity alone was an accurate predictor of splanchnic artery stenosis. Specifically, a peak systolic velocity greater than or equal to 275 cm/sec in the superior mesenteric artery and greater than or equal to 200 cm/sec in the celiac artery or no flow signal (superior mesenteric artery and celiac artery) predicted a 70% to 100% stenosis with sensitivity, specificity, and positive predictive values of 89%, 92%, and 80% for the superior mesenteric artery. Similar values for the celiac artery were 75%, 89%, and 85%, respectively. End-diastolic velocities or calculated velocity ratios conveyed no additional accuracy in predicting splanchnic artery stenosis. PMID- 1920650 TI - A prospective randomized trial of autologous platelet-derived wound healing factors for treatment of chronic nonhealing wounds: a preliminary report. AB - Previous studies have suggested that topically applied platelet-derived wound healing factors (PDWHF) accelerate wound healing by stimulating angiogenesis, fibroblast proliferation, and collagen synthesis. To assess the ability of platelet factors to facilitate healing of chronic cutaneous ulcers we performed a randomized, prospective, double-blind, placebo-controlled study of topical PDWHF in 18 patients with 26 lower extremity wounds refractory to conventional therapy. Wounds were present for at least 8 weeks (mean, 5.5 +/- 4.3 months). They were extensively debrided initially and were measured and photographed at weekly intervals for 12 weeks. Eight patients with nine wounds were treated with placebo solution (controls), and 10 patients with 17 wounds were treated with PDWHF (treatment group). Seventy-eight percent of patients had diabetes mellitus, 72% had occlusive peripheral vascular disease, and 28% had venous disease; distribution of these disorders was equivalent in both groups. Ankle-brachial indexes, which were often spuriously elevated, averaged 0.93 +/- 0.54 in controls and 1.04 +/- 0.56 in patients treated with PDWHF (p greater than 0.5). Mean transcutaneous oxygen tension was 37.8 +/- 11.9 mmHg in controls and 37.1 +/- 9.1 mmHg in patients treated with PDWHF. Initial wound area was larger in controls than in the patients treated with PDWHF (28.9 +/- 45.2 cm2 vs 13.0 +/- 4.4 cm2), but this difference was not statistically significant (p = 0.19). Three (33%) wounds (in two patients) healed in controls, and four (24%) wounds (in three patients) healed in the PDWHF group (p greater than 0.5). The rate of healing in controls was 1.9 +/- 2.7 cm2/week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920651 TI - Pulse oximetry in the evaluation of the painful hand after arteriovenous fistula creation. AB - Five patients with a side-to-side arteriovenous fistula complaining of pain, numbness, and cold sensation were evaluated by pulse oximetry. Low SaO2 was noticed in all five. Closure of a major proximal venous collateral vessel eliminated the steal and resulted in SaO2 correction and was followed by clinical amelioration. Pulse oximetry proved to be a helpful adjunct in the evaluation of the painful hand after creation of an arteriovenous fistula. By applying the pulse oximeter to the patient's affected limb, we were able to determine whether the pain was a result of ischemia and if the correction of the steal improved oxygenation. PMID- 1920652 TI - Determination of the expansion rate and incidence of rupture of abdominal aortic aneurysms. AB - Expansion rate and incidence of rupture of abdominal aortic aneurysms in relation to their size is a source of debate. We studied 114 patients (out of a cohort of 752 consecutive patients admitted with abdominal aortic aneurysms) who were denied any immediate operation because of patient's refusal, high surgical risk, or small transverse diameter as assessed by CT scanning and ultrasonography. All patients not operated on underwent from two to six repeated examinations during an average follow-up period of 26.8 months (range, 3 to 132). Forty-seven patients (41.2%) were subsequently operated on electively because of marked increase of transverse diameter of the aneurysm (n = 44) or for other reasons (n = 3), with a death rate of 0%. Eighteen other patients underwent emergency operation for leaking or ruptured aneurysms, and there were five deaths. The incidence of rupture was clearly related to the final diameter value, rising from 0% in aneurysms less than 40 mm to 22% in large size aneurysms (greater than or equal to 50 mm). Among the 49 patients not operated on, one died of rupture before operation and five of causes unrelated to the disease. Using individual serial measurements, we determined the linear expansion rate of the aneurysm, which proved to be related to initial diameter values: 5.3 mm/year for diameters less than 40 mm (n = 49), 6.9 mm/year in the 40 to 49 mm group (n = 41), and 7.4 mm/year for diameters of 50 mm or more (n = 24).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920653 TI - Leg ulcer etiology--a cross sectional population study. AB - Three hundred eighty-two patients with active leg ulcers were clinically examined after random selection out of a population of 827 patients identified within a previous cross-sectional population survey. Bidirectional Doppler ultrasonography was used for objective assessment of arterial and venous circulation. The purpose was to register causative factors and the etiologic spectrum. Venous insufficiency was present in 332 (72%) of 463 legs with active ulceration; deep insufficiency occurred in 176 (38%), and purely superficial insufficiency was present in 156 (34%). Ankle/brachial index was 0.9 or less in 185 (40%) of ulcerated legs. Venous insufficiency was the dominating causative factor in 250 legs (54%), of which 60% was the result of deep venous insufficiency. Arterial insufficiency was judged to be the possible dominating factor in 12%, and 6% showed clearly ischemic ulcers. Mixed ulcers with combined arterial and venous insufficiency were found to be common as were patients with diabetes and arterial impairment. In 10% of the legs a multifactorial origin was present, and in 10% no venous or arterial impairment was detectable. Thus after classification of causes 40% of all ulcerated legs showed potentially surgically curable circulatory disturbances. It is necessary to objectively assess all patients with chronic leg ulcers to be able to detect patients with potentially surgically curable disease. PMID- 1920654 TI - The influence of elastic compression stockings on deep venous hemodynamics. PMID- 1920655 TI - Carotid endarterectomy: despite the NASCET report, the controversy is not over. PMID- 1920656 TI - Management of postoperative lymphatic leaks by use of isosulphan blue. PMID- 1920657 TI - Epizootiology of avian cholera in wildfowl. AB - Pasteurella multocida, the cause of avian cholera, has naturally infected over 100 species of free-living birds. Among wild birds, avian cholera has its greatest impact on North American wildfowl. Epizootics usually are explosive in onset and may involve thousands of birds. The disease has been reported in every month of the year among wildfowl. Disproportionate mortality, with some species suffering proportionately greater mortality than others, has been a common feature of this disease. Presence of animal organic matter plays a significant role in the survival of P. multocida. There are conflicting reports or a lack of information on the role of host sex, age, body size, other physical features, genetic variation or behavioral differences, as predisposing factors to infection by P. multocida. There also are ambiguities on the relationship between season, precipitation, temperature, nutritional stress, water quality, other microorganisms, and environmental contaminants, and the occurrence of avian cholera in wildfowl. Two competing hypotheses for the year-round reservoir of wildfowl strains of P. multocida are ambient soil or water of enzootic sites, and carrier animals; most current evidence favors the role of carrier animals. Transmission most likely occurs by ingestion of contaminated water, inhalation of bacteria-rich aerosols, or both. While many techniques have been proposed to prevent or control avian cholera, none have been rigorously tested to determine their effectiveness. PMID- 1920658 TI - Haematology and serum biochemistry of captive unsedated chital deer (Axis axis) in Australia. AB - Haematological and serum biochemical values were measured in blood samples collected over a 12-mo period from 37 unsedated chital deer (Axis axis). Stags and hinds, ranging in age from birth to maturity, were sampled. Haemoglobin, total erythrocyte and haematocrit values were low at birth and sex differences were not apparent in neonates and juveniles, but were in adults. Chital stags had higher erythrocyte parameters (P less than 0.001) and lower erythrocyte indices than hinds, and the total leucocyte count was higher in stags (P less than 0.01). Some parameters (erythrocytes, muscle enzymes, glucose, cortisol) decreased over successive serial sampling. The differential leucocyte count of older stags decreased during the initial handling period. The major rutting period in February and March was characterised by changes in the differential leucocyte count, elevations in serum muscle enzymes, and lower serum cortisol levels. Alkaline phosphatase activity in serum reflected the annual antler cycle of chital stags. Serial sampling over many weeks, either weekly or tri-weekly, produced haematological and biochemical changes in successive samples which may have reflected a reduction in stress and excitement associated with restraint. PMID- 1920659 TI - Differences in urinary chemistry profiles of moose on Isle Royale during winter. AB - During winters 1987-1988 (I) and 1988-1989 (II), we assessed the physiological status of moose (Alces alces) residing on the west and east ends of Isle Royale (Michigan, USA) by collecting and chemically analyzing urine deposited in snow (snow-urine) from January to early March. Samples were assayed for urea nitrogen (U), sodium (Na), potassium (K), calcium (Ca), phosphorus (P) and creatinine (C). Throughout both winters, elevated urinary U:C ratios in snow-urine samples collected from east-end moose compared to west-end moose indicated greater dietary energy deprivation and accelerated net catabolism of endogenous protein. Sodium: C ratios were low throughout the study and were similar between moose from both ends of the island, except during the middle of winter I. Greater K:C, P:C and Ca:C ratios in east-end moose compared to west-end moose throughout winter I, and increases in these ratios and U:C in east-end moose from middle to late winter during the second year provided additional evidence of a greater deterioration in condition in east-end moose. The superior nutrition provided to moose on the west end of the island was associated with more developed soils and diverse vegetation and a lower stem density of balsam fir compared to the east end. PMID- 1920660 TI - Hematological and blood chemistry profiles of American bison grazing on Konza Prairie of Kansas. AB - Normal hematological and blood chemistry parameters were measured in 45 American bison (Bison bison) that were divided into three age groups for comparison. There was a statistically significant (P less than 0.05) increase with advancing age in mean corpuscular volume, mean corpuscular hemoglobin, absolute neutrophil and eosinophil counts, total protein, globulin, creatinine, and blood urea nitrogen. There was a statistically significant (P less than 0.05) decrease with advancing age in levels of sorbital dehydrogenase, alkaline phosphatase, glucose, sodium, calcium and phosphorus. PMID- 1920661 TI - Observations of vaginal calculi in dolphins. AB - Vaginal calculi have been described from the common (Delphinus delphis), Pacific white-sided (Lagenorhynchus obliquidens) and spotted (Stenella attenuata) dolphins. We describe additional calculi found in six sexually mature D. delphis from southern California. Three calculi were large (ca. 7 x 5 cm), exhibited concentric layer crystallization, and were unique from previously published descriptions. One calculus described previously and one in our sample appeared to be a fetal skeleton and skull respectively. Using CAT scans of a first trimester northern right whale dolphin (Lissodelphis borealis) and of a near term Delphinus delphis, we discuss the potential origin and development of vaginal calculi through analysis of ossification in embryonic delphinids. We hypothesize that the calculi represented spontaneous incomplete abortion with retention of part or all of the fetus in the distal reproductive tract. The form of the calculus relates to the degree of skeletal development at the time of fetal death. Calculi from a pregnant dolphin provided one measure of residence time. PMID- 1920662 TI - Inflammatory cell stimulation and wound healing in Sphaeridiotrema globulus experimentally infected mallard ducks (Anas platyrhynchos). AB - Thirty laboratory-reared mallard ducks (Anas platyrhynchos) were experimentally infected with Sphaeridiotrema globulus. Host cell-mediated immunity and wound healing in S. globulus infected ducks were evaluated by gross and histological examination. Establishment, location, and life span of S. globulus differed from previous reports of sphaeridiotremiasis in both naturally and experimentally infected waterfowl. No worms were recovered from the ceca, and worm migration occurred anterior to the ileo-cecal valve with greater dispersion (less worm crowding) at higher rates of infectivity. Parasite death and host lesion resolution were evident at days 8 to 10 postinfection (PI) in ducks fed a moderate dose (200 metacercariae, group A) with a 5% mean parasite recovery rate. Host death occurred at days 3 to 6 in ducks fed a high dose (550 metacercariae, group B) with a 16% mean parasite recovery rate. Mast cells increased significantly (P less than 0.005) in group A ducks from days 4 to 10 PI. Eosinophil proliferation was greater in group B than in group A on day 4 PI, but comparatively fewer eosinophils were identifiable in group B ducks on day 6 PI. PMID- 1920663 TI - A comparison between intubation and food addition as routes of oral exposure for northern bobwhites to DDT insecticide. AB - Our objective was to compare two methods of oral dosing of p,p'-DDT (1,1,1 trichloro-2,2-bis (p-chlorophenyl) ethane) on uptake of DDT metabolites and isomers (i.e., p,p'-DDT, o,p'-DDT, p,p'-DDE, o,p'-DDE, p,p'-DDD, o,p'-DDD) in livers and brains. p,p'-DDT was administered to northern bobwhite (Colinus virginianus) by intubation with corn oil or as a feed additive for 56 days. When adjusted for amount of DDT consumed, total DDT (sigma DDT, the summation of all DDT metabolites and isomers) and p,p'-DDE concentrations differed significantly (P less than 0.10) in both brains and livers, whereas p,p'-DDD differed only in brains and p,p'-DDT differed only in livers. Paired comparisons between brains and livers differed significantly for sigma DDT, (P less than 0.05), p,p'-DDE (P less than 0.05) and p,p'-DDT (P less than 0.1) for both intubated and food-dosed treatment groups, whereas p,p'-DDD (P less than 0.05) differed only in the intubated group. We concluded that method of oral exposure affected the uptake of DDT in livers and brains for northern bobwhites. PMID- 1920664 TI - Experimental infection of domestic ferrets (Mustela putorius furo) and Siberian polecats (Mustela eversmanni) with Yersinia pestis. AB - Eight domestic ferrets (Mustela putorius furo) and two Siberian polecats (M. eversmanni) were inoculated subcutaneously with 12 to 1.2 x 10(7) Yersinia pestis originally isolated during an epizootic of plague in white-tailed prairie dogs (Cynomys leucurus) near Meeteetse, Park County, Wyoming (USA) in 1985. None of the ferrets or polecats developed clinical signs of disease which suggested that black-footed ferrets (M. nigripes), a congener, also would be resistant to plague. All animals receiving greater than or equal to 1.2 X 10(3) organisms produced serum antibodies detected by the passive hemagglutination test with titers peaking at 1:1,024 and remaining positive until at least 219 days postinoculation. Sera collected from 12 free-ranging black-footed ferrets near Meeteetse in 1984 and 1985 were negative for antibodies against Y. pestis. Prevalence of antibodies against Y. pestis was high in other carnivores collected from the same area in 1986. PMID- 1920665 TI - Ectoparasites from elk (Cervus elaphus nelsoni) from Wyoming. AB - Hides of nine elk, collected during the winter of 1986-1987 from the National Elk Refuge, Wyoming (USA) were examined for ectoparasites. Parasites recovered were mites, Psoroptes sp. (five elk); lice, Solenopotes ferrisi and Bovicola (Bovicola) longicornis (seven elk); and winter ticks, Dermacentor albipictus (nine elk). Three elk with severe scabies had an estimated 0.6 x 10(6), 3.8 x 10(6) and 6.5 x 10(6) mites, respectively. Densities of mites were much higher in skin regions with severe dermatitis. Skin lesions on elk with scabies consisted of dense, often moist, scabs extending along the dorsal and lateral thoracic regions of the body. Lesions attributed to winter ticks consisted of broken hair and alopecia on the dorsal portion of the lower neck, often extending in a "collar" around the neck. PMID- 1920666 TI - The epidemiology of rodent and lagomorph rabies in Maryland, 1981 to 1986. AB - Records from the Maryland Public Health Department were screened for confirmed rodent and lagomorph rabies between 1981 and 1986. Questionnaires were designed for collection of information about events that led to the exposure of human and/or domestic animals to rabid rodent or lagomorphs. These species comprised 1.2% of all the reported rabies in the state. Woodchucks (Marmota monax) constituted 80.0% of all the reported rodent/lagomorph rabies cases in Maryland. The majority showed aggressive behavior (55.0%). Woodchucks exposed 15 persons (75.0% of all the exposures by rodents/lagomorphs). Domestic animal and human rabies exposure due to rodents and lagomorphs represents a small but significant number of the total exposure to rabid animals. PMID- 1920667 TI - A possible iridovirus in erythrocytes of Bufo marinus in Costa Rica. AB - Icosahedral viral particles were found in the cytoplasm of erythrocytes and splenic reticular cells of a marine toad (Bufo marinus) collected from Costa Rica. Capsids had a maximum diameter of 312 nm and a spherical core with biphasic electron density. Viruses in erythrocytes were associated with cytoplasmic assembly areas and vacuoles in cytoplasm. Nuclei had finely granular material of decreased electron density located centrally, but contained no viral particles. A group of unenveloped viral particles was seen extracellularly in a splenic vessel. The virus was consistent with an iridovirus. In a blood smear stained with Giemsa round basophilic bodies with average diameters of 1.70 microns and morphologically similar to Pirhemocyton sp. were seen in the cytoplasm of erythrocytes and occasionally in the cytoplasm of monocytes or extracellularly. Erythrocytes containing these bodies had vacuoles and irregular pale-staining areas in the cytoplasm and pale-staining areas in the nucleus. These changes corresponded to the viral particles, assembly areas, vacuoles and nuclear changes at the ultrastructural level. PMID- 1920669 TI - Brucella suis infections in collared peccaries in Venezuela. AB - A bacteriologic and serologic study was conducted on two ranches in the states of Apure and Guarico, Venezuela for brucellosis in collared peccaries (Tayassu tajacu). One hundred thirty-nine peccaries were necropsied and tissues were cultured. Forty-three isolations of Brucella suis biovar 1, were made from lymph nodes and spleens of 25 males and 18 females. Antibody to Brucella sp. was detected in sera from 122 animals by the rapid plate agglutination, standard tube agglutination, 2-mer-captoethanol, rivanol, complement fixation and card tests. Young animals had infection and reactor rates nearly as high as the older animals indicating most were infected at a relative early age. Results suggest that this species may transmit brucellosis when living with domestic animals. This is the first report of B. suis biovar 1 from collared peccaries in Venezuela. PMID- 1920668 TI - Experimental Brucella suis biovar 4 infection in a moose. AB - A moose (Alces alces gigas) was inoculated with Brucella suis biovar 4 to better understand the effects of brucellosis in this species. Serum antibody titers increased rapidly and peaked within 21 to 56 days. Fever, leukocytosis, recumbency, anorexia and depression were observed starting 42 days post inoculation. Brucella suis biovar 4 was isolated from blood, lymph nodes, liver and spleen. PMID- 1920670 TI - Blood parasites of blue grouse (Dendragapus Obscurus) in western North America. AB - Three hundred thirty-three blue grouse (Dendragapus obscurus) were examined for blood parasites from 11 sites: southern Yukon Territory, southeast coastal Alaska, northern and central interior British Columbia, south coastal British Columbia, northcentral Washington, southcentral Oregon, northwestern California, eastcentral Nevada, northwestern Colorado, and westcentral Montana. Three species of protozoan parasites (Leucocytozoon lovati, Haemoproteus mansoni, Trypanosoma avium) and a splendidofilariid nematode (Microfilaria sp. B) were found in nearly all locations. Prevalence levels were consistently high for L. lovati (92%). The other hematozoa were found less frequently (H. mansoni 29%; T. avium 46%; and microfilaria 29%). The range of these parasites in blue grouse was extended to a more northern (Yukon Territory) and more southern distribution (Nevada than previously reported. Ranges were also extended to blue grouse populations in Alaska, Washington, Oregon and California. PMID- 1920671 TI - Hemoparasites of raccoons (Procyon lotor) in Florida. AB - Four hemoparasite species (Babesia lotori, Trypanosoma cruzi, Dirofilaria tenuis and Mansonella llewellyni) were found in raccoons (Procyon lotor) collected from 1972 to 1974 in Duval (n = 14) and Collier (n = 170) counties, Florida (USA). Trypanosoma cruzi was found in thin blood smears from one raccoon at each locality. The prevalence of B. lotori was 79% and 80% in samples taken in December 1973 in Collier and Duval counties, respectively. No patent infections by B. lotori were detected in raccoons collected in Collier County in December 1972, but 42% of the raccoons examined in September 1973 were infected. In Collier County there were no significant differences in the prevalence of B. lotori by host sex or age. In Duval County, overall D. tenuis prevalence was 7%, whereas that of M. llewellyni was 14%; the latter species was not found in Collier County. Adult raccoons had a significantly greater prevalence of D. tenuis (32%) than did subadults and juveniles (7%), and male raccoons showed a significantly greater prevalence (51%) than did females (8%). PMID- 1920672 TI - The frequency of Sarcocystis spp. and its effect on winter carcass composition of mottled ducks. AB - Macrocysts of the protozoan parasite Sarcocystis spp. occurred in 34 of 241 (14%) adult and 6 of 70 (8.6%) immature mottled ducks (Anas fulvigula) that were collected in southwestern Louisiana from 1987 to 1989. The prevalence of Sarcocystis spp. among immature ducks was higher than previously reported, possibly because of a longer exposure period. No differences in carcass composition variables were found between heavily infected and uninfected adult mottled ducks during the winter period of the annual cycle. We concluded that macrocysts of Sarcocystis spp. did not influence carcass composition and probably exert negligible effects on survival of parasitized mottled ducks during winter. PMID- 1920673 TI - Helminth parasites of unisexual and bisexual whiptail lizards (Teiidae) in North America. V. Mesocestoides sp. tetrathyridia (Cestoidea: Cyclophyllidea) from four species of Cnemidophorus. AB - Two hundred and one whiptail lizards, Cnemidophorus spp., from Texas and Colorado (USA), were examined for Mesocestoides sp. tetrathyridia. Eleven (5%) were infected, including three of 58 (5%) C. dixoni, six of 70 (9%) C. gularis septemvittatus, one of 35 (3%) C. marmoratus, and one of 34 (3%) C. tesselatus; four C. inornatus heptagrammus were not infected. In addition, 41 non cnemidophorine lizards from the same study area were not infected. Free tetrathyridia were found in the body cavity of lizards and encapsulated tetrathyridia were observed in the heart, liver, stomach, mesenteries, ovaries, intestines, and lungs. None of the Mesocestoides sp. exhibited any evidence of asexual proliferation such as multiple scoleces or buds. This note, the fifth in a series of reports on helminths of Cnemidophorus spp., represents the first time Mesocestoides sp. has been reported from these four taxa, and Colorado is a new geographic locality record for this parasite. PMID- 1920674 TI - Parasitism in captive and reintroduced red wolves. AB - Fecal examinations revealed that at least 10 of 21 (48%) captive red wolves (Canis rufus) and eight of 12 (67%) free-ranging red wolves were infected with intestinal parasites. No captive wolves and only one of seven reintroduced wolves had dirofilariasis. Ticks were collected from 10 of 21 (48%) captive wolves and nine of 12 (75%) free-ranging animals. Ivermectin administered at a dosage of 50 micrograms/kg of estimated body weight every 30 to 60 days apparently prevented or ameliorated parasitism in red wolves. PMID- 1920676 TI - Hematological and serum chemistry values for Arabian oryx (Oryx leucoryx). AB - Blood samples obtained from 73 captive Arabian oryx (Oryx leucoryx) were analyzed for hematology and serum chemistry values. Compared with other data from this animal RBC, WBC, bilirubin and ASAT values are lower, but glucose, urea and uric acid values are higher. PMID- 1920675 TI - Glycosylated hemoglobin as a stable alternative to serum glucose in white-tailed deer. AB - We compared serum glucose concentration and percent glycosylated hemoglobin (GH) in captive and wild white-tailed deer (Odocoileus virginianus) to determine stability of glucose relative to GH. Temporal changes in levels of serum glucose and GH were ascertained from serial blood samples collected from three captive deer over a 2-week period. State of glycemia also was determined for 17 wild deer that were collected from three populations in southeastern Oklahoma and southwestern Arkansas (USA). Concentration of serum glucose of captive deer decreased (P = 0.04) from 190.4 to 155.8 mg/dl over the 2 weeks; percent GH did not differ temporally (P = 0.30). Percent GH of wild deer did not differ (P = 0.23) when deer were separated into 2 groups (high and low state of glycemia) based on the median serum glucose concentration. We found a significant difference (P = 0.04) in percent GH among wild deer populations; serum glucose concentration did not differ (P = 0.72) among populations. Our results indicate that percent GH is more stable than serum glucose concentration and may be useful in population comparisons of nutritional condition. PMID- 1920677 TI - Dietary vitamin and mineral concentrations of two juvenile female giant pandas (Ailuropoda melanoleuca). AB - During a 7 mo exhibit loan, diets of two juvenile female giant pandas (Ailuropoda melanoleuca) were monitored. Mineral [calcium (Ca), copper (Cu), phosphorus (P), potassium (K), zinc (Zn)] and vitamin (beta-carotene and total tocopherol) concentrations in the diet were quantified as well as in a serum sample obtained from one of these animals. Diets consumed by the pandas contained (dry matter basis): 0.82% Ca, 0.62% P, 1.05% K, 14.3 mg/kg Cu, 31.8 mg/kg Zn, 12.2 mg/kg beta carotene, and 12 mg/kg total tocopherol. Serum values for these vitamins and minerals were within reported normal limits for the spectacled bear (Tremarctos ornatus). This diet appeared to provide adequate nutrition for maintenance and growth. PMID- 1920678 TI - Proventricular impaction associated with nonsuppurative encephalomyelitis and ganglioneuritis in two Canada geese. AB - Two wild Canada geese (Branta canadensis) in an extremely emaciated state and with severe proventricular food impaction also had a nonsuppurative encephalomyelitis and ganglioneuritis. The condition in these two birds was morphologically similar to psittacine proventricular dilatation, a recently identified disease of psittacine birds. PMID- 1920679 TI - Squamous cell carcinoma in a free-ranging bighorn sheep (Ovis canadensis californiana). AB - An oral squamous cell carcinoma which invaded maxillary bones with metastasis to the right retropharyngeal lymph node was diagnosed in a free-ranging California bighorn sheep (Ovis canadensis californiana) from Washington. Much of the maxillae had been replaced with tumor and reactive tissue, and many teeth were missing or loose. The tumor was predominantly confined to the shape of the maxillary bones and was unusual because it was bilaterally symmetrical. PMID- 1920680 TI - A case of leukemia in the desert spiny lizard (Sceloporus magister). AB - A leukemia characterized by the proliferation of undifferentiated hematopoietic stem cells is described from a desert spiny lizard (Sceloporus magister). This is the first neoplasm reported from this species and the first leukemia from the family Iguanidae. A massive invasion of primitive hematopoietic cells was noted in the vascular system and heart muscle. Spleen, bone marrow, lungs, adrenal gland, pancreas, brain, skin, testes, liver, lamina propria and submucosa of intestines were extensively involved. Tissue-fixed mast cells were noted in the kidney and intestinal submucosa but were not participating in the neoplastic proliferation. PMID- 1920681 TI - African lineage, hypertension linked. PMID- 1920682 TI - Congressional AIDS commission in limelight, likely to remain there for another year. PMID- 1920683 TI - Third vaccine for Haemophilus influenzae? PMID- 1920684 TI - First infection-fighting monoclonal antibodies scrutinized by FDA Advisory Committee members. PMID- 1920685 TI - Vaccine for meningococcal meningitis tested. PMID- 1920686 TI - From the National Institutes of Health. PMID- 1920687 TI - From the Agency for Health Care Policy and Research. PMID- 1920688 TI - From the Centers for Disease Control. Tuberculosis outbreak among HIV-infected persons. PMID- 1920690 TI - From the Centers for Disease Control. Homicide followed by suicide--Kentucky, 1985-90. PMID- 1920689 TI - From the Centers for Disease Control. Current tobacco, alcohol, marijuana, cocaine use. PMID- 1920691 TI - A piece of my mind. Her daughter, her doctor. PMID- 1920692 TI - Caring for the uninsured and underinsured. PMID- 1920693 TI - Retired physicians are willing to work. PMID- 1920694 TI - Inoculating blood cultures: changing needles is useful. PMID- 1920695 TI - The blood pressure of hypertensive smokers. PMID- 1920696 TI - Malpractice claims data as a quality improvement tool. I. Epidemiology of error in four specialties. AB - OBJECTIVE: --To identify potentially preventable sources of medical injury in obstetrics and gynecology, general surgery, anesthesiology, and radiology. DESIGN: --Retrospective review of physician malpractice claim records. SETTING: - Large New Jersey physician malpractice insurer. PARTICIPANTS: --Physicians practicing obstetrics and gynecology, general surgery, anesthesiology, and radiology and covered by the insurance carrier during any portion of 1977 through 1989. MAIN OUTCOME MEASURES: --Proportion of claims due to negligence associated with errors in (1) patient management, (2) technical performance, and (3) medical and nursing staff coordination and the clinical and financial consequences of such errors. RESULTS: --Among 1371 claims ascribed to negligence, patient management errors were cited most frequently in all four specialties (48% to 75%) and, compared with performance and coordination problems, were generally associated with a higher frequency of serious injury and higher median payments. Coordination problems accounted for about 9% of claims. In obstetrics and gynecology, newborn delivery claims usually arose from management errors (57% to 68%), whereas gynecologic procedure claims were most often associated with performance errors (55% to 73%). Underperformance of cesarean section was cited more frequently than overperformance (31% vs 3%). General surgery claims were about equally divided between management and performance types regardless of procedure. Failure to perform appropriate diagnostic testing or monitoring was the main problem in 3% to 8% of claims. CONCLUSION: --Malpractice data can be used to identify problem-prone clinical processes and suggest interventions that may reduce negligence. PMID- 1920697 TI - Malpractice claims data as a quality improvement tool. II. Is targeting effective? AB - OBJECTIVE: --To evaluate the usefulness of malpractice claims data for identifying (1) physicians who are prone to negligent errors and (2) physician and hospital characteristics associated with particular kinds of errors. DESIGN: -Retrospective review of physician malpractice claim records. SETTING: --Large New Jersey physician malpractice insurer. PARTICIPANTS: --Physicians practicing obstetrics and gynecology, general surgery, anesthesiology, or radiology and covered by the insurance carrier for any portion of 1977 through 1989. MAIN OUTCOME MEASURES: --Claims were classified into 11 clinical error categories comprising three broad groups: patient management problems, technical performance problems, and staff coordination problems. Outcomes were expressed as per physician frequency of claims due to negligence and proportion of claims associated with various types of errors. RESULTS: --Using 5 years of claims history to predict long-term claims proneness was more accurate than chance alone by 57% in obstetrics and gynecology, 33% in general surgery, 11% in anesthesiology, and 15% in radiology. Cross-validated recursive partitioning showed that among physician characteristics, only specialty was predictive of physician error profiles. For physician claims arising in acute care hospitals, hospital size and location in addition to hospital services discriminated among different error profiles; the cross-validated accuracy of this method was 69% compared with 22% accuracy achieved by random prediction. CONCLUSION: --Use of physicians' malpractice claims histories to target individuals for education or sanctions is problematic because of the only modest predictive power of such claims histories. PMID- 1920698 TI - Failure of exercise to reduce blood pressure in patients with mild hypertension. Results of a randomized controlled trial. AB - OBJECTIVE: --To assess the effects of physical exercise training on blood pressure in patients with mild hypertension. DESIGN: --Randomized controlled trial. SETTING: --Hospital-based cardiac rehabilitation program. PATIENTS: - Ninety-nine men and women with untreated mild hypertension (systolic blood pressure, 140 to 180 mm Hg; diastolic blood pressure, 90 to 105 mm Hg) were included in the volunteer sample. INTERVENTIONS: --Subjects were randomly assigned to a 4-month program of aerobic exercise training, strength and flexibility training, or to a waiting list control group. MAIN OUTCOME MEASURES: -The main outcome measures were systolic and diastolic blood pressures measured four times with a random zero sphygmomanometer on 3 separate days in a clinic setting. RESULTS: --After 4 months of exercise training, subjects in the aerobic exercise group did not exhibit greater reductions in blood pressure than subjects in the control group. We expected a differential decline of 5 mm Hg between the aerobic exercise and waiting list control groups and found a difference of -1.0 +/- 16 mm Hg and -1.2 +/- 10 mm Hg at alpha = .05 for systolic and diastolic blood pressure, respectively. CONCLUSIONS: --Moderate aerobic exercise alone should not be considered a replacement for pharmacologic therapy in nonobese patients with mild hypertension. PMID- 1920699 TI - The politics of local tobacco control. AB - Until the nonsmokers' rights movement, tobacco control activity was at the federal or state levels, which is where the tobacco industry dominates. Since the appearance of the nonsmokers' rights movement, progress in tobacco control has occurred primarily at the local level. In response to the success of this movement, the tobacco industry has developed "smokers' rights" groups and other tactics to fight local legislation. Several recent local campaigns in California illustrate these tactics. Tobacco control forces follow many paths, from sitting on the sidelines to making a serious commitment to smoking control legislation. Despite the tobacco industry's superior financial resources, the outcome of proposed local tobacco control legislation appears to depend on how seriously the health advocates mobilize in support of the local legislation. When the health community makes a serious commitment of time and resources, it wins. When it fails to make such a commitment, the tobacco industry prevails, more by default than by its superior financial resources. PMID- 1920700 TI - Pseudomalabsorption of levothyroxine. AB - OBJECTIVE: --The issue of patient compliance with pharmacological therapy vs malabsorption of medication was explored in the context of persistent hypothyroidism despite the administration of large doses of levothyroxine sodium. DESIGN: --Retrospective case series. SETTING: --Referred care in two large tertiary care centers. PATIENTS: --Four patients, seen within two decades, with clinical and biochemical hypothyroidism while receiving levothyroxine, were evaluated for selective malabsorption of this hormone. INTERVENTIONS: --Studies included serial measurements of thyroid hormone levels after a loading dose of levothyroxine or liothyronine sodium or evaluation with a double-labeled thyroxine tracer technique. Results were compared with studies of levothyroxine malabsorption in the medical literature. RESULTS: --All patients were ultimately found to have normal (82% to 100%) absorption of oral levothyroxine. There was no evidence that malabsorption of levothyroxine can occur as an isolated abnormality. CONCLUSIONS: --Some patients exhibit a factitious disorder suggesting malabsorption of levothyroxine. When treating hypothyroidism, psychiatric issues may result in noncompliance with levothyroxine therapy. PMID- 1920701 TI - Buffer solutions may compromise cardiac resuscitation by reducing coronary perfusion presssure. AB - OBJECTIVE: --To investigate the effects of hypertonic buffer solutions on coronary perfusion pressure (CPP) and resuscitability during experimental closed chest cardiac resuscitation. DESIGN: --Randomized, placebo-controlled trial. SETTING: --Mammalian research laboratory. PARTICIPANTS: --Forty-four domestic pigs. INTERVENTIONS: --Cardiac arrest was induced by ventricular fibrillation in mechanically ventilated pigs anesthetized with pentobarbital sodium. Precordial compression was started at the third minute of untreated ventricular fibrillation and maintained for an interval of 8 minutes. A hypertonic solution of sodium bicarbonate, Carbicarb (an equimolar mixture of sodium bicarbonate and sodium carbonate [International Medication Systems, Ltd]), or sodium chloride or an isotonic solution of sodium chloride was infused into the right atrium over a 1 minute interval starting at the sixth minute of ventricular fibrillation. Restoration of spontaneous circulation was attempted by DC transthoracic countershock after 11 minutes of ventricular fibrillation. MAIN OUTCOME MEASURES: --Plasma osmolality, CPP, and cardiac resuscitability. RESULTS: --Infusion of hypertonic buffer and sodium chloride solutions increased plasma osmolality from an average of 280 to 330 mOsm/kg. This was accompanied by a significant decrease in the aortic pressures and CPPs generated during precordial compression. No such changes occurred after infusion of isotonic sodium chloride. Restoration of spontaneous circulation, as in earlier studies, was contingent on the levels of CPP prior to attempted defibrillation. Accordingly, none of 13 animals in which the CPP declined to less than 10 mm Hg after infusion of the hypertonic solutions were successfully resuscitated. This contrasted with nine animals that received isotonic sodium chloride and served as controls. Coronary perfusion pressure consistently exceeded 10 mm Hg in these control animals, and spontaneous circulation was restored in each instance. CONCLUSIONS: --Hypertonic solutions and specifically buffer solutions administered in the absence of vasopressor agents may adversely affect cardiac resuscitation efforts by reducing CPP below critical thresholds. PMID- 1920703 TI - To thwart the tobacco companies. It's every physician's responsibility. PMID- 1920702 TI - Administrative case rounds. Institutional policies and leaders cast in a different light. PMID- 1920704 TI - Oregon's methods. Did cost-effectiveness analysis fail? PMID- 1920705 TI - Insurance loss threatens medical gain. PMID- 1920707 TI - Anonymously(?) authored book urges violence. PMID- 1920706 TI - Gene scene: studies begin to yield clues about disease progression after HIV infection. PMID- 1920708 TI - Eventual central nervous system regeneration? PMID- 1920709 TI - Gene replacement therapy enters second year. PMID- 1920710 TI - Seeking to detect hearing loss at earlier age. PMID- 1920711 TI - From the Centers for Disease Control. Nosocomial infection and pseudoinfection from contaminated endoscopes and bronchoscopes--Wisconsin and Missouri. PMID- 1920712 TI - From the Centers for Disease Control. Self-induced malaria associated with malariotherapy for Lyme disease--Texas. PMID- 1920713 TI - Photolocalized varicella in an adult. PMID- 1920714 TI - Gifts to physicians from industry. PMID- 1920715 TI - Pregnant surgical residents: Oh K?! PMID- 1920716 TI - Homicide among adolescents in the United States. PMID- 1920717 TI - Searching question: on-line or CD-ROM? PMID- 1920718 TI - Diminishing diagnostic returns. PMID- 1920719 TI - A product warning label to encourage prepregnancy control of diabetes. PMID- 1920720 TI - Fatal asthma attack after inhaling sulfur fumes. PMID- 1920721 TI - Discrepancies in the reported frequency of cocaine-related deaths, United States, 1983 through 1988. AB - OBJECTIVE: --To assess the validity of cocaine-related mortality data available from the principal federal sources of information about the frequency of drug abuse deaths in the United States: the national vital statistics system and the Drug Abuse Warning Network (DAWN). DESIGN, SETTING, AND PARTICIPANTS: --We compared the number of cocaine-related deaths reported to national vital statistics and DAWN from 25 metropolitan areas during the years 1983 through 1988. We also compared cocaine-related mortality data reported to national vital statistics with data from all published forensic case series of cocaine-related deaths that occurred during the mid-1980s. RESULTS: --During the 6-year study period, 75% more cocaine-related deaths were reported to DAWN (6057) than to national vital statistics (3466) from the 25 metropolitan areas that were studied. For individual metropolitan areas, the discrepancy between DAWN and vital statistics counts of cocaine-related deaths was as large as a sixfold difference. In six of the seven forensic case series identified in our literature search, the number of cocaine-related deaths exceeded the number of these deaths reported to vital statistics. The largest discrepancy was for cocaine-related deaths in New York, NY, during a 10-month period in 1986 for which 151 deaths were reported in a case series and seven deaths were reported to vital statistics. CONCLUSION: --Improvements in existing public health surveillance systems are needed for (1) full and accurate measurements of the lethal impact of drug abuse epidemics and (2) valid and comprehensive assessments of the effectiveness of national programs designed to prevent drug-related morbidity and mortality. PMID- 1920722 TI - The emergency department as a pathway to admission for poor and high-cost patients. AB - BACKGROUND: --To determine the importance of the emergency department as the means of access to the hospital for the poor and the fiscal implications of providing these services, we examined the relationship between patients' socioeconomic status and admission via the emergency department. We also determined the association between entering the hospital via the emergency department and hospital resource use. METHODS: --We conducted a study of 20,089 patients admitted to five Massachusetts hospitals (three community, two tertiary care) during a 6-month period. We determined the proportions of patients within various socioeconomic and disease groupings who entered through the emergency department. We compared length of stay and charges for patients admitted through the emergency department with those for patients admitted through other routes. RESULTS: --Overall, 51% of patients entered via the emergency department. Elderly patients (age greater than 65 years; odds ratio, 1.87) and patients with lower socioeconomic status as measured by income, occupation, and education (odds ratios, 2.38, 1.47, and 1.69, respectively) were more likely to enter the hospital via the emergency department than other patients. After adjustment for diagnosis related group, severity as measured by DRGSCALE, and socioeconomic status as measured by income, and excluding outliers, patients admitted via the emergency department stayed 27% longer and incurred 13% higher charges than other patients (P less than .001). CONCLUSIONS: --Our data indicate that patients with lower socioeconomic status are more likely than other patients to use the emergency department as their means of access to the hospital and that patients admitted via the emergency department use far more resources than patients in the same diagnosis related group admitted by other means. Hospitals that make emergency department services more available may be more likely to hospitalize socioeconomically disadvantaged patients and may be at a substantial financial disadvantage under per-case reimbursement systems such as Medicare. PMID- 1920723 TI - Excess infant mortality in an American Indian population, 1940 to 1990. AB - OBJECTIVE: --To describe the infant mortality experience of an American Indian community and to demonstrate the utility of examining community-level mortality data. DESIGN: --Descriptive, population-based historical review of infant death certificates. SETTING: --The Warm Springs Indian Reservation, Oregon. PATIENTS OR OTHER PARTICIPANTS: --Infant tribal members of the Confederated Tribes of Warm Springs, 1940 to 1990. INTERVENTIONS: --None. MAIN OUTCOME MEASURES: - Categorization of causes of infant deaths and calculations of mortality rates. RESULTS: --The infant mortality rate, while lower in each decade since the 1940s, was still 2.6 times the national (all races) rate in the 1980s. Neonatal deaths did not account for many of the excess deaths. The postneonatal mortality rate has consistently been much greater than the national rate and was five times greater in the 1980s. Almost all of the excess infant mortality since 1980 has been due to the sudden infant death syndrome. CONCLUSIONS: --While there has been a dramatic decrease in infant mortality for this American Indian population, it remains higher than the national rate. Examining the causes of infant death has enabled this population to develop focused strategies to reduce infant mortality. PMID- 1920724 TI - Bacteriology of acute otitis media in adults. AB - OBJECTIVE: --The objective of this study was to determine the bacteriology of acute otitis media in adults. Although this has frequently been studied in children, no data have recently been reported from adults in the United States. Additionally, information on the prevalence of Haemophilus influenzae as a causative organism in acute otitis media in adults has not been available. DESIGN: --Middle-ear aspirates for cultures were obtained by myringotomy from adults meeting entry criteria. SETTING: --Emergency department, Eye and Ear Hospital of Pittsburgh, Pa. PATIENTS: --Thirty-four patients (volunteer sample) met the eligibility requirements. Exclusion criteria included history of chronic otitis media, recent antibiotic therapy, immunosuppressive illnesses, or prior otologic surgery. INTERVENTION: --Ten days of oral cefuroxime axetil (250 mg) was prescribed. MAIN OUTCOME MEASURES: --Patients were followed closely for at least 6 weeks. Aerobic and anaerobic cultures were incubated and evaluated per the scheduled protocol. RESULTS: --Haemophilus influenzae and Streptococcus pneumoniae were grown on culture of specimens from nine and seven patients (26% and 21%), respectively. Twenty-two percent (2/9) of the H influenzae isolates and the single isolate of Moraxella catarrhalis produced beta-lactamase (9% overall). CONCLUSIONS: --The present results suggest that, as in children, amoxicillin would be an appropriate first-line agent for empiric therapy of acute otitis media in adults. Antimicrobials inactive against H influenzae (eg, penicillin V, cephalexin, erythromycin, or tetracyclines) are not appropriate for initial therapy. Antimicrobials with efficacy against organisms producing beta-lactamase, such as cefuroxime axetil, which was used to treat the study patients, do not appear to be required for routine initial therapy in adults. However, they would be appropriate when an organism producing beta-lactamase is isolated from the middle ear or when a patient fails to improve rapidly on amoxicillin therapy. PMID- 1920725 TI - Care of women infected with the human immunodeficiency virus. AB - OBJECTIVE: --To review current knowledge regarding human immunodeficiency virus (HIV) infection in women and to derive from that data standards of care. DATA SOURCES: --Selective review of pertinent articles addressing cervical disease, pelvic inflammatory disease, sexually transmitted diseases, contraception, and pregnancy in HIV-infected women. A computer-assisted search was used to identify relevant articles on pharmacokinetics of drugs in women and oral contraceptive- drug interactions. DATA EXTRACTION: --Pertinent data were abstracted from case control, cohort studies, clinical trials, and pharmacokinetic studies. DATA SYNTHESIS: --Few studies have been performed to define the clinical course of HIV infection in women. Gender-specific manifestations, such as cervical neoplasia, pelvic inflammatory disease, and vaginal moniliasis, appear to pursue a more aggressive course in HIV-infected women. Little is known about the pharmacokinetics of drugs for HIV and related infections. Oral contraceptives may alter the metabolism of some drugs used in HIV-infected women. An approach to the routine treatment of HIV-infected women is summarized. CONCLUSIONS: --Little is currently known regarding the natural course of HIV infection in women. Women infected with HIV should be followed up frequently with specific attention paid to the reproductive system. Additional studies should be conducted to determine the impact of HIV on gender-specific diseases. PMID- 1920726 TI - Human immunodeficiency virus infection in diabetic intravenous drug users. AB - OBJECTIVE: --To evaluate the association between diabetes and human immunodeficiency virus (HIV) seroprevalence in a population of intravenous (IV) drug users. DESIGN: --Cross-sectional survey in a cohort of IV drug users. SETTING: --Community-based study clinic. SUBJECTS: --The study included 2921 individuals with a history of IV drug use in the past 10 years; over 90% had injected drugs in the past year and 77% in the past month; only 15% were receiving drug treatment. OUTCOME MEASURES: --The HIV seroprevalence among IV drug users with and without a history of diabetes. RESULTS: --Those IV drug users with a history of diabetes had significantly lower HIV seroprevalence (9.8%) than nondiabetic IV drug users (24.3%; P = .03). Despite similar duration and intensity of drug use and sexual practices, diabetic IV drug users tended not to share injection paraphernalia and were less likely to attend shooting galleries than nondiabetic IV drug users. CONCLUSION: --Our data suggest that the apparent protective effect of diabetes against HIV infection in IV drug users is most likely due to their safer injection practices afforded by their ready access to sterile injection equipment. PMID- 1920728 TI - Tracking the cocaine epidemic. The Drug Abuse Warning Network. PMID- 1920727 TI - Primary care and health. A cross-national comparison. AB - Ten Western industrialized nations were compared on the basis of three characteristics: the extent of their primary health service, their levels of 12 health indicators (eg, infant mortality, life expectancy, and age-adjusted death rates), and the satisfaction of their populations in relation to overall costs of the systems. Information was derived primarily from published sources. Indices were developed to characterize the extent of primary care in each country and the standing of each country relative to the others on the health indicators. There was general concordance for primary care, the health indicators, and the satisfaction-expense ratio in nine of the 10 countries. Ratings for the United States were low on all three measures. West Germany also had low ratings. In contrast, Canada, Sweden, and the Netherlands had generally high ratings for all three measures. The lack of concordance in the ratings in the United Kingdom may be a result of relatively low expenditures for other social services and public education in that country. The findings may add to the debate and deliberations concerning modifications in organization and financing of care that are currently being considered in the United States. PMID- 1920730 TI - Hospital admission through the emergency department. The obstructed pathway. PMID- 1920729 TI - Monitoring the impact of cocaine. PMID- 1920731 TI - Macular degeneration: is aspirin a risk for progressive disease? PMID- 1920732 TI - Reversing anorgasmia associated with serotonin uptake inhibitors. PMID- 1920733 TI - Some (not all) influenza watchers suggest 'bad season' lies ahead. PMID- 1920734 TI - Good intentions do pave road to safe harbors, but taking contravention avenues remains risky. PMID- 1920735 TI - Despite some overlap, ethical and legal issues of physician self-referral remain distinct. PMID- 1920736 TI - National Institutes of Health: North and South. PMID- 1920738 TI - From the Centers for Disease Control. Weapon-carrying among high school students. PMID- 1920737 TI - From the National Institutes of Health. PMID- 1920739 TI - A piece of my mind. A single tear. PMID- 1920740 TI - Diapers and day care. PMID- 1920741 TI - Sterility of Norplant packaging. PMID- 1920742 TI - Kids, cholesterol, carotids, and coronaries. PMID- 1920743 TI - Hypermagnesemia-induced hypotension and hypoventilation. PMID- 1920744 TI - Torsades de pointes occurring in association with terfenadine use. PMID- 1920745 TI - Human immunodeficiency virus infection in disadvantaged adolescents. Findings from the US Job Corps. AB - OBJECTIVE--To describe the human immunodeficiency virus (HIV) epidemic among socially and educationally disadvantaged young persons in the United States. DESIGN: -We analyzed demographic and geographic findings from the screening of Job Corps students for antibody to HIV. SETTING--The Job Corps is a federal training program for disadvantaged, out-of-school youth. POPULATION SCREENED- Residential students aged 16 to 21 years who entered the Job Corps from October 1987 through February 1990. MAIN OUTCOME MEASURE--Rates of observed HIV infection in entering students, stratified by demographic and geographic features. RESULTS- Of 137,209 Job Corps students screened, 488 were HIV seropositive (3.6 per 1000), a seroprevalence rate higher than that among military applicants of the same age. Overall seroprevalence was slightly higher in male (3.7 per 1000) than in female (3.2 per 1000) Job Corps students, but among those students aged 16 and 17 years, seroprevalence was higher among females (2.3 per 1000) than among males (1.5 per 1000) (P less than .05). For students aged 16 to 21 years, seroprevalence increased with year of age: 1.8 per 1000 per year for males and 0.7 per 1000 per year for females. Among those aged 21 years, HIV prevalence was 8.9 per 1000. For black and Hispanic students from large Northeastern cities, seroprevalence increased by 4.3 per 1000 per year of age and reached 24.8 per 1000 (one of 40) in students aged 21 years. However, among students from rural areas and small towns, HIV seroprevalence was disproportionately high in the Southeast. Compared with recently described US patients with the acquired immunodeficiency syndrome, HIV-infected students who entered the Job Corps were much more likely to be female. CONCLUSIONS--These findings show that disadvantaged, out-of-school adolescents are at high risk for HIV infection. The screening results identified surprisingly high seroprevalence in the southeastern United States and demonstrated a marked shift in the HIV epidemic to young women. Controlling the HIV epidemic among teenagers must include interventions that will reach adolescents early and outside of the formal educational system. PMID- 1920746 TI - The role of the pneumatic antishock garment in penetrating cardiac wounds. AB - OBJECTIVE--To determine the impact of the pneumatic antishock garment on survival in patients with cardiac wounds. DESIGN--A retrospective review of a 6.5-year experience in a population of patients with gunshot or stab wounds to the heart (N = 70). SETTING--The city and county of Denver, Colo, where all patients were transported by paramedic ambulances to Denver General Hospital, an urban, level 1 trauma center. PATIENTS--All patients were analyzed, including those transported to the emergency department with no vital signs at the trauma scene. Only patients with definite penetrating cardiac injuries were included. METHODS- Paramedic trip sheets and emergency department, operating room, in-hospital, and autopsy records were reviewed. Demographic, clinical outcome, and treatment data were collected. A multiple logistic regression model was developed to determine which characteristics and treatment variables were independently predictive of patient outcome. The ability of each independent variable to predict outcome was determined by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS--Seventy patients (31 gunshot and 39 stab wounds) had a revised trauma score of 2.8 +/- 4.0 (mean +/- SD; range, 0-12; median, 0). Thirty-two (46%) had cardiac tamponade. Overall, 21 (30%) of the patients survived. In the logistic model, the presence of cardiac tamponade (OR, 9.1; 95% CI, 1.5 to 56.1) and a higher revised trauma score were associated with higher survival. Inflation of the pneumatic antishock garment was associated with sevenfold lower survival (adjusted OR, 0.14; 95% CI, 0.02 to 0.86); the effect was negative across all trauma score groups. CONCLUSION: --Survival in patients with penetrating cardiac wounds is highly associated with anatomic and physiologic factors, while application of the pneumatic antishock garment appears to be detrimental. PMID- 1920747 TI - Diagnosis and treatment of ischemic stroke. PMID- 1920748 TI - Evidence for the effects of HIV antibody counseling and testing on risk behaviors. AB - OBJECTIVE: To review published abstracts, journal articles, and presentations for evidence of the effects of human immunodeficiency virus (HIV) antibody counseling and testing on risk behaviors. Studies reviewed focused on homosexual men, intravenous drug users in treatment programs, pregnant women, and other heterosexuals. DATA SOURCES: Peer-reviewed journals (January 1986 through July 1990) and published abstracts and oral presentations from the second (1986) through the sixth (1990) International Conferences on AIDS. STUDY SELECTION: We identified 66 studies that included data on the behavioral effects of HIV antibody counseling and testing. By consensus of the authors, 16 of these were excluded because of small sample size or inadequate study design. DATA EXTRACTION: Studies were assessed by the authors according to methodological strength (sample selection, inclusion of appropriate comparison groups, and inclusion of statistical tests of significance). DATA SYNTHESIS: All longitudinal studies of homosexual men reported reductions in risky behavior among both tested and untested men, and a few reported greater decreases among seropositive men than among seronegative men and those untested or unaware of their serostatus. For intravenous drug users in treatment, we found reductions in intravenous drug use and sexual risk behaviors regardless of counseling and testing experience. We found little evidence for the impact of counseling and testing on pregnancy and/or pregnancy termination rates for either seropositive or seronegative high risk women. We noted substantial risk reduction among heterosexual couples with one infected partner. Findings among other heterosexuals at increased risk were scanty and mixed. CONCLUSIONS: Further studies should specifically address the behavioral consequences of counseling and testing in various settings. PMID- 1920750 TI - DNR in the operating room. Not really a paradox. PMID- 1920749 TI - Mandatory HIV testing of youth. A lose-lose proposition. PMID- 1920751 TI - Oregon's plan. Should it be approved? PMID- 1920752 TI - Responsibility for integrity lies first with students. PMID- 1920754 TI - In search of integrity. PMID- 1920753 TI - Cheating in medical schools: implications for students and patients. PMID- 1920755 TI - How can we deter cheating in medical school? PMID- 1920756 TI - Emotional rescue. PMID- 1920757 TI - BCG vaccination. PMID- 1920758 TI - Perinatal mortality in Jinnah Postgraduate Medical Centre, Karachi. AB - During the one year period from 1st January to 31st December, 1989, there were 6,826 deliveries and 695 perinatal deaths, of these 553 were still-born and 142 were neonatal deaths (died within 7 days of birth). The perinatal mortality rate was 101.8 per thousand total births. The still-birth rate was 81 per thousand total births. Of the perinatal deaths, 7.9% occurred in booked and 92.1% in non booked cases. The commonest cause of death was antepartum haemorrhage (APH), 24.2% followed by mechanical which accounted for 23.6% deaths. Abruptio placentae was the leading cause among all still-births and low-birth weight (LBW) in all neonatal deaths. PMID- 1920759 TI - Transcutaneous bilirubinometry in Pakistani newborns: a preliminary report. AB - Neonatal hyperbilirubinemia is a frequently encountered problem in the neonatal period and carries a potential risk of encephalopathy. Early detection and quantification is important, and transcutaneous bilirubinometry (TcB) has been recommended as a non-invasive method for rapid screening. We prospectively compared the efficacy of TcB in 65 normal Pakistani jaundiced newborns undergoing simultaneous serum bilirubin measurements. Although the correlation between the two methods was significant (r = 0.66, P less than 0.01), the scatter was wide and the specificity only 53%. Although the technique offers the potential for non invasive early screening of neonatal hyperbilirubinemia, it requires further validation in a larger study in our population. PMID- 1920760 TI - Detection of coliform organisms in drinking water by radiometric method. AB - The radiometric method has been used for detection of coliform bacteria in water. The method is based on measuring the released metabolic 14CO2 from 14C-lactose in growth media containing coliform organisms incubated at 37 degrees C under continuous shaking. This rapid and sensitive radiometric method permits the detection of even single coliform organisms within 6 hours of incubation. Using this automated method, a total of 102 samples (in duplicate) collected from different areas in and around Rawalpindi and Islamabad were assessed for coliform bacteria. Of these 102 samples, 50 were tap water samples, 40 from wells and 6 each were from Rawal and Simly dams. About 47% and 67% tap water samples, while 62% and 74% well water samples were found unsatisfactory from around Islamabad and Rawalpindi areas, respectively. About 83% and 66% water samples from Rawal dam and Simly dam respectively were found to be unsatisfactory. PMID- 1920761 TI - A clinicopathological analysis of ovarian tumours. AB - We performed a retrospective analysis of patients with ovarian tumors who were admitted to the Aga Khan University Hospital from January 1985 to December 1989. Sixty one cases were reviewed. Mean age of the whole group was 44 years. Majority of the patients presented with abdominal pain and distention. Most frequent physical finding was a palpable mass on pelvic or abdominal examination. Overall these patients had a higher incidence of breast cancer than expected in the general population. Two-thirds of the tumors were malignant. Comparison of the patients with malignancy against those with benign tumors failed to show any correlation with parity. Majority of the patients with malignant disease were above forty and had ultrasound showing a cystic mass over 10 cms in size. Cancer was mostly epithelial in origin, with widespread disease (stage III or IV) at the time of presentation. Benign tumors, mostly of germ cell type, were predominantly seen in patients under the age of forty with ultrasound showing cystic mass of any size from under 5 cms to over 10 cms. PMID- 1920762 TI - Maternal factors affecting birthweight of uncomplicated pregnancy. AB - Two hundred full-term pregnant mothers with no complication of pregnancy and no associated disease selected from Jinnah Postgraduate Medical Centre were studied for their nutritional status and other characteristics. The effect of these factors on birthweight of their new-born was determined. Total calorie intake per capita per day was low being 1913. The mean birthweight was 2.9kg, 26% weighed 2.5kg or less. No significant sex difference was observed in the birthweight. Variables having a significant positive influence on birthweight were maternal age at first delivery, up to 25 years, beyond which correlation was not significant; maternal weight and maternal total calorie intake (irrespective of source) up to an intake of 2500 calorie per day, beyond which correlation was not significant. Combined effect of these three maternal factors on birthweight was highly significant. Coefficient of correlation, R being 0.81. PMID- 1920763 TI - Local preparation, standardization and quality control of technetium labelled macroaggregated albumin for lung perfusion studies. AB - Lung perfusion study is an important investigation in various pulmonary diseases. The radiopharmaceutical commonly used now-a- days is imported macroaggregated human albumin (in kit form), which is labelled with technetium (Tc99m-MAA). Due to its high cost the technique could not be fully exploited. We have tried to locally prepare freeze dried MAA particles. Various parameters like concentration of protein, pH value, temperature, quality and quantity of reducing agents were studied to find out the optimum conditions for radiolabelling and the desired particle size. More than 98% of the added radioactivity was found tagged to the MAA particles in the final preparation (confirmed by paper chromatography). Labelled agent was found to be radiochemically stable for up to 6 hours. Initial animal and later human studies showed an ideal spectrum of particle size. PMID- 1920764 TI - Glycation and diabetic complications. PMID- 1920765 TI - Spontaneous haemorrhage in goitre causing respiratory distress. PMID- 1920766 TI - Severe hypernatraemia in a very preterm infant. AB - Hypernatraemia in very low birth weight babies has been well documented and is usually attributable to excessive insensible water loss. We report a case in which, despite a peak serum sodium concentration of 204 mmol/l, the baby survived without morbidity. Treatment was simply to increase the intake of free water in Dextrose. PMID- 1920767 TI - The multi-disciplinary approach to choledocholithiasis. PMID- 1920768 TI - Lead--an essential trace element. PMID- 1920769 TI - [Preparation of the diagnostic criteria for body surface mapping]. PMID- 1920770 TI - [Diagnostic criteria for arrhythmia]. PMID- 1920771 TI - [Prevention and management of juvenile heart diseases]. PMID- 1920772 TI - [Pathogenesis, therapy, and prevention of myocardial diseases and myocarditis]. PMID- 1920773 TI - [Diagnostic criteria for exercise tests]. PMID- 1920774 TI - [Disabilities after fractures of the femur]. PMID- 1920775 TI - [Recent developments in the pharmacology and clinical use of pentazocine]. AB - Pentazocine, an agonist-antagonist of opioid receptor, has been used widely in Japan especially for the control of acute pain. This is because of the tight regulation on the use of narcotics in Japan. Cases of addiction to pentazocine, however, have been observed and in 1990 the drug was designated as a psychomimetic drug of the second degree. Special attention should be paid in storing the drugs of this category in hospitals. In this short review on pentazocine, the pharmacology and clinical use of pentazocine were reviewed including nature of agonist-antagonist drug, potentiality for addiction, pharmacokinetics, and its effect on central nervous, respiratory and circulatory systems. Toxic manifestations after excess doses of pentazocine as well as the local tissue change in response to its repeated injections were also reviewed. PMID- 1920777 TI - [End-tidal carbon dioxide concentration during cardiopulmonary resuscitation in patients with pre-hospital cardiac arrest]. AB - This study was done to clarify whether end-tidal carbon dioxide (ETCO2) concentration is an effective monitor as an indicator of survival and prognosis of patients who arrived with cardiac arrest. We measured ETCO2 concentration in 30 patients with pre-hospital cardiac arrest during cardiopulmonary resuscitation (CPR). Six patients were resuscitated successfully and the others were not. The values of ETCO2 of the resuscitated patients, at the time of starting advanced life support were varied from 0 to 4.5% (mean 1.4%), which were not different from the values in patients who were not resuscitated (mean 0.87%). In 13 patients who were not resuscitated, the initial values of ETCO2 during CPR were below 1.0%, whereas the other 11 patients showed high ETCO2 values (above 1.5%), which were dependent on the degree of chest compression. This suggests that ETCO2 monitoring during cardiopulmonary resuscitation is a good non-invasive indicator to evaluate the efficacy of chest compression itself, but its initial values during CPR are not correlated with success of resuscitation in patients with pre hospital cardiac arrest. PMID- 1920776 TI - [Effects of mannitol on the function of red blood cells]. AB - The effects of mannitol on the function of red blood cell were studied in 12 neurosurgical patients for 4 hours after intravenous administration of 2 g.kg-1 mannitol taking 30 min. After the administration of mannitol, osmotic pressure, Na and K in serum and of red blood cell were all altered. P50, 2, 3-DPG rose gradually and red blood cell deformity improved significantly. These results indicate that mannitol can shift oxyhemoglobin dissociation curve rightward, improve red blood cell deformity, and increase tissue oxygenation significantly. Mannitol administration not only decreases intracranial pressure but also improves peripheral circulation and oxygen transport during brain resuscitation. PMID- 1920778 TI - [Evaluation of pulmonary capillary wedge pressure tracing for the detection of intraoperative myocardial ischemia]. AB - We studied the usefulness of the pulmonary capillary wedge pressure (PCWP) tracing for the detection of intraoperative myocardial ischemia. Both PCWP wave forms and 7-lead electrocardiogram were monitored in 109 patients undergoing coronary artery bypass graft surgery. Measurements were made six times in each patient. Myocardial ischemia was identified in 99 (27%) of the 366 measurements, and among them, 68 (69%) developed abnormal PCWP wave forms (AC wave greater than 15 mmHg, or V wave greater than 20 mmHg). Although these results were consistent with those of Kaplan et al (1981), we could not agree with their conclusion that PCWP tracing can be helpful in the early diagnosis of subendocardial ischemia. It was not possible to record PCWP continuously because of the risk of pulmonary infarction, and PCWP was influenced by noncardiac factors such as sympathetic reaction to surgical stimuli. We think that PCWP tracing would be of benefit in detecting intraoperative serious ischemia; serious myocardial ischemia was likely to have occurred when abnormalities in both PCWP tracing and ST segment changes were identified. The incidence of both PCWP changes and ECG ischemia was highest in the postbypass period, suggesting that the risk of serious myocardial ischemia is highest in the post-bypass period. PMID- 1920779 TI - [Solubility of desflurane (I-653), sevoflurane, isoflurane, and halothane in human blood]. AB - The blood/gas partition coefficients for the new volatile anesthetic agent desflurane (I-653), sevoflurane, isoflurane, and halothane were determined, simultaneously, in 8 human volunteers to compare the solubilities of these agents in blood. The blood/gas partition coefficient for desflurane [0.49 +/- 0.03 (mean +/- SD)] was smallest, followed by sevoflurane (0.62 +/- 0.04), isoflurane (1.27 +/- 0.06), and halothane (2.46 +/- 0.09). Differences among the anesthetic agents were significant (P less than 0.001). The results of this study confirm that among these agents the solubility of desflurane in human blood is the smallest. The results suggest that the washin and washout of desflurane will be more rapid than that of sevoflurane, isoflurane, and halothane, and the washin and washout of sevoflurane will be more rapid than that of isoflurane and halothane. PMID- 1920780 TI - [A comparison of the endocrine effects of hypotension induced by nicardipine with those by sodium nitroprusside in dogs]. AB - Plasma catecholamines, plasma renin activity, plasma aldosterone and plasma cortisol during hypotension induced by sodium nitroprusside and nicardipine were studied in 27 mongrel dogs under 0.87% halothane in oxygen. They were randomly divided into three groups: sodium nitroprusside (group S: n = 8), nicardipine (group N: n = 8) and controls (group C: n = 9). Group C received no vasodilator therapy and served as a control. Mean arterial pressure was reduced and maintained at 60 mmHg for 60 minutes in hypotensive groups. No changes were noted in plasma catecholamines and plasma cortisol in group C throughout the experiment, but plasma renin activity and plasma aldosterone decreased progressively. During hypotension induced by sodium nitroprusside and nicardipine, plasma epinephrine was significantly higher than the control value. However, after the hypotensive drugs were discontinued, plasma epinephrine decreased slightly. During and after induced hypotension, plasma renin activity of group N and group S were significantly higher than the control values. The highest levels of plasma renin activity 36.7 ng.ml-1.hr-1 in group N and 23.2 ng.ml-1.hr-1 in group S were observed. Plasma aldosterone concentration was significantly higher than the control value in group N. The maximum increase occurred 30 minutes after discontinuation of the nicardipine and the highest concentration of plasma aldosterone was three times control value. In contrast, in group S, plasma aldosterone was unchanged from the control value. Plasma cortisol concentration of group N was significantly increased than the control value. However, in group S, plasma cortisol concentration showed a slight but not significant increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920781 TI - [A study on lipid peroxidation in neonates--(2). Perioperative changes in serum lipid peroxide and superoxide dismutase activity]. AB - Pre-, intra-, and post-operative changes in serum lipid peroxide: malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were studied in 10 neonates aged from 15 hours to 26 days. The results are summarized as follows: 1) Preoperative serum MDA levels were significantly lower than those of normal neonates. No significant difference was found between pre- and post-operative values, although much fluctuations were observed in neonates within 7 days of age. All the individual values returned to the normal range during the early postoperative period with different respiratory management. 2) Changes in serum SOD activity were similar to those in MDA values. The activity seemed to be higher and more sensitive to oxygen concentration in younger neonates, which may suggest the specific antioxidant properties of the neonates. 3) Postoperatively, serum MDA levels tended to increase following intravenous administration of lipid emulsion. 4) There was a positive correlation between the values of serum MDA and SOD activity, especially in neonates within 7 days of age. PMID- 1920782 TI - [Effects of clonidine premedication upon hemodynamic changes associated with laryngoscopy and tracheal intubation]. AB - The authors studied 30 patients undergoing general anesthesia in order to evaluate whether oral clonidine premedication could attenuate the hemodynamic changes associated with laryngoscopy and tracheal intubation. Patients were randomly assigned to one of two groups; clonidine group (n = 15) who received oral clonidine of approximately 5 micrograms.kg-1, or control group (n = 15) who received no clonidine. The magnitude of increases in mean blood pressure from baseline values following laryngoscopy and tracheal intubation in the clonidine group was significantly smaller as compared with that in the control group (20 +/ 12 vs. 31 +/- 14 mmHg, mean +/- SD, P less than 0.05). There was also a significant difference between the two groups in the incidence of systolic blood pressure increases above 180 mmHg following laryngoscopy and tracheal intubation (0% vs. 26%, P less than 0.05). However, no significant difference was noted between the two groups in the heart rate responses to laryngoscopy and tracheal intubation. It is concluded that oral clonidine of 5 micrograms.kg-1 as a preanesthetic medication could attenuate the pressor responses associated with laryngoscopy and tracheal intubation. PMID- 1920784 TI - [Effects of halothane on spinal dorsal horn WDR(wide dynamic range) neuronal activity in cats]. AB - The effects of halothane (0.2%, 0.5%, and 1.0%) on the spinal dorsal horn wide dynamic range (WDR) neuronal activity was studied in either spinal cord intact or spinal transected cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind foot pads of intact or decerebrate, spinal cord transected (L 1-2) cats. When 10 micrograms of bradykinin was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus in the spinal cat, all of 7 WDR neurons gave excitatory responses which were not depressed by 0.2% and 0.5% halothane but were depressed significantly by 1.0%. On the other hand, when the injection of 10 micrograms of bradykinin into the femoral artery ipsilateral to the recording site was used in the intact cat, 7 of 14 WDR neurons (50%) gave excitatory responses, which were not depressed by 0.2% halothane but were significantly depressed by 0.5% and 1.0% halothane, and 7 of 14 WDR neurons (50%) gave inhibitory responses, which were significantly depressed by 0.2%, 0.5%, and 1.0% halothane. We have found that halothane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by bradykinin injection. PMID- 1920783 TI - [Interpleural administration of 1.0% and 1.5% lidocaine with epinephrine for pain relief after thoracotomy]. AB - Pain relief following thoracotomy and arterial concentration profiles after interpleural administration of lidocaine were studied in 23 adult patients. They were allocated to three groups and given interpleural injection of 20 ml each of 1.0% (group 1, N = 9, non-pneumonectomy patients), 1.5% (group 2, N = 10, non pneumonectomy patients), and 1.5% (group 3, N = 4, pneumonectomy patients) lidocaine with epinephrine (5 micrograms.ml-1). Complete pain relief was obtained within 20 min after injection in all patients. The mean duration of analgesia was 2.8 hr, 3.1 hr, and 5.1 hr in group 1, 2, and 3, respectively. The maximum plasma concentrations of lidocaine (Cmax) were 1.7 +/- 1.0 (mean +/- SD) microgram.ml-1, 2.2 +/- 0.6 micrograms.ml-1, and 0.7 +/- 0.2 micrograms.ml-1 in group 1, 2, and 3, respectively. The mean duration of analgesia was significantly longer in group 3 than in group 2 (P less than 0.01). Cmax was significantly lower in group 3 than in group 2 (P less than 0.01). In conclusion, we consider interpleural injection of lidocaine with epinephrine to be an effective method of providing postoperative analgesia after thoracotomy. Our data also suggest that the duration of analgesia may increase and the plasma levels of lidocaine may remain quite low in total pneumonectomy patients, because local anesthetic solution is not absorbed through the visceral pleura but absorbed only through the parietal pleura alone in these patients. PMID- 1920785 TI - [Hyponatremia during transurethral resection of the prostate]. AB - In a retrospective study of 222 patients who underwent transurethral resection of the prostate under spinal anesthesia, plasma sodium levels during the operation were examined. The weight of prostate resected, the volume of irrigating fluid used and the duration of the operative procedure influenced the changes in plasma sodium levels. But, these changes were not statistically significant. The rise in central venous pressure values was associated with the absorption of irrigating fluid as evidenced by a drop in plasma sodium. The central venous pressure was monitored in 77 patients. There was a statistically significant correlation between the degree of hyponatremia and the rise in central venous pressure (P less than 0.001). The rise in central venous pressure reflected a change in the patient's cardiovascular status and it was, therefore, possible to treat the hyponatremia quickly and effectively. Central venous pressure monitoring is helpful in determining hyponatremia before it becomes clinically manifest. PMID- 1920786 TI - [The effect of extradurally administered analgesics on somatosensory evoked eyelid microvibration in rabbits]. AB - We examined the effect of various analgesics administered lumboextradurally or intravenously on acceleration of the eyelid microvibration (EMV) due to reflex contraction which was evoked by electrical stimulation of the sciatic and ulnar nerve in rabbits. No significant difference in the inhibition of EMV was observed initially between the sciatic nerve and the ulnar nerve stimulated group after 2 mg of morphine, administered either extradurally or intravenously. However, greater inhibition of EMV by the extradural morphine than by intravenous administration of this drug was observed after 10 min in sciatic nerve stimulated and after 20 min in the ulnar nerve stimulated group. With the extradural administration of 0.05 mg fentanyl, EMV was inhibited more significantly in the sciatic stimulated group than in the ulnar nerve stimulated group. Intravenous administration of this drug failed to reveal any change in either sciatic nerve stimulated or ulnar nerve stimulated group. When butorphanol 0.5 mg or buprenorphine 0.05 mg was administered, no significant difference in the inhibition of EMV was observed between the drugs, regardless of the routes of administration or sites of stimulation. Extradural administration of ketamine 0.5 mg showed none of the inhibition of EMV in both the sciatic nerve stimulated, and the ulnar nerve stimulated groups. These results indicate that various analgesics administered into the extradural space produced characteristic actions depending on the pharmacokinetic properties of each drug, locally and/or generally. In conclusion, monitoring of EMV can be a useful procedure for evaluation of the effect of analgesics. PMID- 1920787 TI - [Continuous intravenous infusion of pethidine or buprenorphine for postoperative analgesia]. AB - Efficacy of continuous intravenous infusion for postoperative analgesia was evaluated in 20 patients who had undergone abdominal surgery for 72 hours postoperatively. The patients were randomly allocated to two groups: one group received continuous intravenous infusion of buprenorphine at 0.2 mg.24 hr-1 using a non-electronic, portable infusor 0.5 ml.hr-1 type (Baxter), while the other received infusion of pethidine at 50 mg.hr-1. During the first 12 postoperative hours, the frequency of "Fair" rating which indicated need of supplemental analgetics was significantly higher than the later 12-hour period until 72 hours in both groups. However, although during the first 12 hours continuous intravenous infusion was inadequate to alleviate postoperative pain compared with other 12-hour period, no patient received supplemental analgesics more than 2 times. During the 24 to 72 postoperative hours, 70% of cases needed no supplemental analgesics to alleviate postoperative pain. Continuous intravenous infusion of 0.2 mg.hr-1 buprenorphine or 50 mg.hr-1 pethidine was inadequate for postoperative analgesia during immediately after the operation to 36 hours postoperatively, especially during the first 12-hour period. However, this infusion was effective during 36 to 72 postoperative hours. There was no significant difference between buprenorphine group and pethidine group. PMID- 1920788 TI - [The CO2 absorption capacity and color indication of a newly developed soda lime (Wakolime)]. AB - The CO2 absorption capacity and the color change of ethyl violet (color indicator) of Wakolime A (newer type). Wakolime (older type), and Sorb 800 were studied under the clinical anesthetic condition. A two chamber canister was filled with soda lime and anesthetic gas flowed upward through the canister at the rate of 4 ml.min-1. The wall temperature of each chamber was measured with surface temperature sensing device. After 30 hours of use, the colored soda lime in the first chamber was examined with a color analyzer. The change of wall temperature indicated that the CO2 absorption capacity of Sorb 800 was the largest and that of Wakolime was the smallest among the three. The indicator color of both Wakolime A and Sorb 800 was clearer and of more vivid violet than that of Wakolime, which was dull and grayish. These results indicated that Wakolime A is superior in the CO2 absorption capacity and color indication to Wakolime. PMID- 1920790 TI - [A report on 107 cases of obturator nerve block]. AB - The obturator nerve passes in close proximity to the inferolateral bladder wall. Transurethral resection of bladder tumors close to these areas may stimulate the obturator nerve, causing violent adductor contraction and possible inadvertent bladder perforation. To avoid this reaction, local anesthetic blockade of the obturator nerve as it passes through the obturator canal is effective to stop adductor spasm during spinal anesthesia. We performed obturator nerve block in 107 cases by use of insulated needle and nerve stimulator, and measured the depth of the obturator nerve and that of the pubic tubercle. Obesity index was positively correlated with the depth of the obturator nerve as well as the pubic tubercle. However, no correlation was found between the obesity index and the difference of the depth of the obturator nerve and the depth of the pubic tubercle. It is suggested that if the needle is advanced in the direction of the obturator canal about 40mm further after reaching the pubic tubercle, the needle reaches the obturator nerve. PMID- 1920789 TI - [Anesthetic management of revascularization for moyamoya disease]. AB - Anesthetic management during 85 STA-MCA anastomoses with or without encephalo myosynangiosis for 64 patients with Moyamoya disease was evaluated retrospectively. Anesthetic agents included nitrous oxide-NLA (GONLA), nitrous oxide-halothane (GOF), nitrous oxide-enflurane (GOE), and their combinations. Slight hypercarbia (40 mmHg less than PaCO2 less than 50 mmHg) was essential to avoid cerebral ischemia. Several procedures to control heart rate by beta blockade or to control hypertension by nitroglycerin were required, because tachycardia and hypertension interfered with fine surgical procedure. During microsurgery HR of GONLA anesthetized patients was significantly lower. Postoperatively the patients anesthetized by GOE showed significantly lower PaCO2 compared with the GONLA anesthetized patients. So we recommend GONLA for anastomosis in patients with Moyamoya disease. PMID- 1920791 TI - [Terminology in anesthesia]. PMID- 1920792 TI - [The relationship between the deep body temperature and hemodynamics after open heart surgery]. AB - The relation of the forehead-sole deep body temperature difference with the cardiac index (CI), and the relation of that with the systemic vascular resistance index (SVRI) were studied in 61 adult patients after open-heart surgery for 24 hours. A correlation between the deep body temperature difference (X) and CI (Y) was expressed as, Y = -0.21X + 3.42 (r = 0.48), and that between the deep body temperature difference (X) and SVRI (Y), Y = 184X + 808 (r = 0.52). But immediately after the end of operation (n = 61), the correlation coefficients (r) were lower, 0.46 and 0.45, respectively. The deep body temperature difference was 1.8 degrees C on the average in patients whose CI was 2.21.min-1.m-2, and was 4.3 degrees C in patients whose CI was below 2.21.min-1.m-2. Conversely CI was below 2.21.min-1.m-2 in patients whose deep body temperature difference was more than 4 degrees C. We conclude that the measurement of deep body temperature difference is useful as a circulatory monitor, and that a critical level of deep body temperature difference is 4 degrees C. PMID- 1920793 TI - [Blood levels of lidocaine during continuous epidural anesthesia as indicated by leg skin temperature]. AB - Arterial blood concentrations of lidocaine were measured in 7 patients undergoing pancreas operation during continuous epidural anesthesia and repeated doses of lidocaine were given according to the skin temperature of the toe. After the epidural catheter placement at the middle level of thoracic spine, 3 ml (test dose) plus 9 ml of 2% lidocaine with epinephrine (1:200,000) were injected. Additional doses of lidocaine, 6 ml, were injected when the skin temperature of the toe decreased for 0.3 degrees C. Two cases were excluded from this study because the skin temperature did not increase following additional doses of lidocaine. Lidocaine was added for 3.4 times on an average during anesthesia (duration 345 +/- 35 min, mean +/- SE). The first, second, third and fourth intervals of repeated injections from the initiation of epidural anesthesia were 119 +/- 10 min, 184 +/- 16 min, 251 +/- 20 min and 323 +/- 27 min, respectively. Arterial blood concentrations of lidocaine before each injection were 2.4 to 2.8 micrograms.ml-1 and these values showed no significant changes. These results demonstrate that the estimation of the necessity of additional injections by monitoring the skin temperature during prolonged epidural anesthesia prevents the lidocaine intoxication. PMID- 1920794 TI - [The effects of prostaglandin E1 on the granulocyte elastase, white blood cells and platelets in head-neck surgery]. AB - We studied whether prostaglandin E1 (PGE1) inhibits the granulocyte elastase increase, white blood cell increase and platelet decrease caused by surgical stimuli in 30 head-neck surgical patients. The patients were divided into a group of no PGE1 infusion (C group) and two groups of PGE1 infusion (infusion of 10 ng.kg-1.min-1 in P 10 group and infusion of 30 ng.kg-1.min-1 in P 30 group). PGE1 was infused intravenously using a syringe pump during operation. The granulocyte elastase, white blood cells and platelets were measured at 4 points: before induction of anesthesia, before surgery, 4 hours after the start of surgery or the infusion of PGE1, and on the first postoperative day. Granulocyte elastase was maintained at significantly higher levels during and after surgery in 3 groups. White blood cells correlated with granulocyte elastase in 3 groups (especially in C group; Granulocyte elastase = 1.48 X white blood cells + 23.5, r = 0.672). Platelets decreased significantly in the first postoperative day in C and P 10 group. PGE1 has a tendency to inhibit dose-dependently the postoperative decrease in platelets. We conclude that 30 ng.kg-1.min-1 infusion of PGE1 did not inhibit granulocyte elastase release from white blood cells, but has a tendency to inhibit postoperative platelet decrease. PMID- 1920795 TI - [Protective effects of PGE1 on postoperative liver function after gastric cancer surgery]. AB - The effects of PGE1 on liver function tests in patients who underwent gastric cancer surgery were studied. PGE1 was administered in 13 patients at a rate of 20 100 ng.kg-1.min-1 (PGE1 group) during surgery. Fourteen patients served as the control group. On the first postoperative day, SGOT and SGPT increased in both groups. But on the first and the third postoperative days, SGPT of the PGE1 group was significantly lower (P less than 0.05) than that of the control group. Five patients in the control group showed transaminase above 100 IU.l-1 in the postoperative period. In contrast, no patient showed this increase in the PGE1 group. These findings indicate that continuous infusion of PGE1 during surgery is beneficial in attenuating hepatic injury. PMID- 1920796 TI - [The effect of local anesthetics on the isolated human right atrial appendages- 1: A comparison of inhibition of contractility with bupivacaine and lidocaine]. AB - The inhibition of cardiac muscle contractility with bupivacaine was about tenfold of that with lidocaine, namely the ID50 values of bupivacaine and lidocaine were 10(-6) M and 10(-5) M, respectively. With bupivacaine above 3 x 10(-6) M, the contraction was diminished completely. In the medium of a high calcium concentration (Ca2+:5.0 mM), the effect of lidocaine (10(-5) M) was antagonized markedly, but that of bupivacaine was not antagonized so much. These results suggest that they might have some different mechanisms in respect to the inhibition of the contractility, for instance bupivacaine affecting mainly sarcoplasmic reticulum and lidocaine affecting mainly sarcolemma. PMID- 1920798 TI - [Preoperative evaluation of patients with disturbed respiratory functions]. AB - It is difficult to predict the occurrence of postoperative pulmonary complications. We analyzed correlation between postoperative pulmonary complications and pre-operative pulmonary functions in patients with severely disturbed respiratory functions; i.e. %VC of under 50% or FEV1% of under 50%, for the past 6 years. Pulmonary complications developed in 15 of the 137 patients studied (10.9%). Of the 108 patients with preoperative %VC of under 50%, pulmonary complications developed in 7 patients (6.5%). Of the 29 patients with preoperative FEV1% under 50%, pulmonary complications developed in 8 patients (27.5%). We found that postoperative pulmonary complications correlate well with preoperative FEV1%. PMID- 1920797 TI - [The effect of local anesthetics on the isolated human right atrial appendages- Part 2: Bupivacaine is different from lidocaine concerning the mechanism of inhibition of contractility]. AB - With regard to the inhibition of contractility, dose-response curves of ryanodine and nickel were produced, and in these curves ID50 values were 10(-6) M and 2 x 10(-3) M, respectively. ID50 of bupivacaine was similar to ryanodine's and that of lidocaine was between ryanodine and nickel. On the post-rest potentiation (PRP) elicited after 2 s of rest following a train of stimulation at 3 Hz, ryanodine and bupivacaine had similar depressing effects, but lidocaine depressed it moderately and nickel showed no effect. These results suggest that bupivacaine could cause a direct inhibitory effect on sarcoplasmic reticulum (SR) function like ryanodine, but lidocaine could cause mainly a reduction in trans-sarcolemmal Ca influx and induce a slight inhibitory effect on SR function. PMID- 1920799 TI - [Is ventilatory anaerobic threshold useful for preoperative assessment?]. AB - The anaerobic threshold (VAT), obtained by measurement of ventilatory volume and by expiratory gas analysis, and the anaerobic threshold (LAT), obtained directly from the lactic acid value in the blood, were compared and evaluated during exercise load in 25 patients with mitral valve disease. Exercise loading was performed with an ergometer using a multistep method of increases of 5 W (Group A, 11 cases) or 10 W (Group B, 14 cases) per minute. The oxygen uptake value at the points of 0.5 mmol.l-1 and 1.0 mmol.l-1 increase in the lactic acid values when compared with the starting values were designated as 0.5 LAT and 1.0 LAT. VAT was found in 4 of 11 (36%) patients in Group A and in 12 of 14 (86%) patients in Group B and the ratio obtained was significantly higher in Group B than in A. The 0.5 LAT values for Group A and B were 2.4 +/- 0.5 and 2.2 +/- 0.3, respectively. The 1.0 LAT values were 2.9 +/- 0.7 and 2.7 +/- 0.4, and among the two groups no significant difference was found concerning 0.5 LAT or 1.0 LAT. VAT was seen in 16 or 25 patients and the average VAT value of the 16 was roughly at the midpoint between the average values for 0.5 LAT and 1.0 LAT. Therefore in patients in which VAT was seen with the expiratory gas method, VAT and LAT values were basically equivalent. However, in Group A, VAT was seen in only 4 of 11 patients and it is a fact that it is difficult to find VAT without a suitable exercise load. PMID- 1920800 TI - [An analysis of the ventilatory response to carbon dioxide during halothane, isoflurane, or enflurane anesthesia in humans]. AB - To analyze the effects of halothane, isoflurane, or enflurane on the ventilatory response to CO2, minute volume (VE), respiratory rate (f), occlusion pressure, mean inspiratory flow rate (VT/TI), and effective elastance (Pmax/VT) were measured in 26 patients during quiet breathing and when the respiratory system was stressed by CO2. Comparison was made at equipotent anesthetic concentration (1 MAC) and all measurements were made in the absence of surgical stimulation. Respiratory rate and Pmax/VT were unchanged in all groups after end-tidal CO2 was elevated. By contrast, VE, VT/TI, and occlusion pressure increased in all the groups when the respiratory system was stressed by CO2. Among the parameters tested delta VE/delta PaCO2 and delta VT/TI/delta PaCO2 were significantly (P less than 0.05) greater during halothane anesthesia than during isoflurane or enflurane anesthesia. We conclude that, at equipotent anesthetic concentrations, isoflurane and enflurane depress CO2 chemosensitivity more than halothane does, and that such effect is primarily related to the greater depressant effects of isoflurane and enflurane on the respiratory driving mechanisms. PMID- 1920801 TI - [Influence of duration of complete global brain ischemia on neurologic outcome in dogs]. AB - The author studied the influence of duration of complete global brain ischemia (CGBI) on neurologic outcome (NO) in dogs. The CGBI of various durations, from 10 to 20 minutes, were induced by clamping of the ascending aorta combined with bypass formation between the aorta and the right atrium. The dogs were divided into four groups according to the duration of CGBI: dogs in group A, B, C or D suffered 10, 15, 18 or 20 minutes of CGBI respectively. In four groups, NOs were evaluated for 7 days after the ischemic insult. In group A, no significant damages were observed and all survived for 7 days. In group B, marked differences in the degree of neurologic deficits were observed, and nearly a half were almost normal and the remainder were severely damaged. In groups C and D, all were so severely damaged as to become vegetative and any difference in the degree of neurologic deficits was not observed among the groups. The author concludes that dogs which have suffered CGBI for 15 minutes or less are not suitable for use in order to evaluate the efficacy of treatments for ischemic brain damage with NOs, and that dogs which suffered CGBI for 18 minutes or more are appropriate for this purpose. PMID- 1920803 TI - [Diaphragmatic fatigue and its recovery are influenced by markedly decreased cardiac output: possible involvement of neuromuscular junction]. AB - Effects of highly decreased cardiac output on the development and recovery of diaphragmatic fatigue were studied in dogs. The fatigue was induced by supramaximal electrical stimulation (20 Hz) of phrenic nerves for 30 minutes. Cardiac output was reduced during this period to 30% of control value by mechanically obstructing inferior vena cava with a balloon in animals with lowered cardiac output group (lowered Qt group). Cardiac output was maintained at normal value throughout the experiment in animals of the other group (control group). The animals were observed for recovery for 60 minutes after induction of the fatigue. The standardized transdiaphragmatic pressure (Pdi/Pdi 100) and integrated electromyographic activity (Edi/Edi 100) elicited by electrical test stimuli (20, 100 Hz) were significantly lower in lowered Qt group (P less than 0.01) during entire fatigue and recovery period. The decrease of Pdi/Pdi 100 and Edi/Edi 100 at high frequency test stimuli (100 Hz) was observed only in lowered Qt group. These results suggest that when cardiac output is severely decreased the diaphragm is more susceptible to fatigue, and that this may be caused by a failure of neuromuscular junction as well as by an impaired excitation contraction coupling. PMID- 1920802 TI - [Nitroglycerin reduces requirement of pancuronium in surgical patients]. AB - We performed a study on 34 adult surgical patients between 15 and 56 years of age, to evaluate whether synergism between nitroglycerin and pancuronium exists or not. Neuromuscular (NM) transmission was measured by electromyography of the thenar muscle using transcutaneous electrodes. Anesthesia was induced by droperidol 0.2 mg.kg-1, fentanyl 50 micrograms, thiamylal 150-250 mg, and succinylcholine 1 mg.kg-1, and maintained with nitrous oxide and O2 (67:33) supplemented with repeated i.v. doses of fentanyl (within 15 micrograms.kg-1). Pancuronium 4 mg was given at the 20% recovery from succinylcholine induced NM block. Sequential i.v. doses of pancuronium 1 mg were injected repeatedly at the every 20% recovery until the end of operation. To control blood pressure, nitroglycerin, ranging from 0 to 5 micrograms.kg-1.min-1, was given intravenously. The linear multiple regression analysis was performed between the dose of pancuronium (micrograms.kg-1.hr-1) and the dose of nitroglycerin (micrograms.kg-1.min-1), the age, sex, or body weight of the patients. The results show that the dose of pancuronium decreases with increasing dose of nitroglycerin. No relationship was found between the dose of pancuronium and the age, sex, or body weight of the patients. In conclusion, nitroglycerin reduces requirement of pancuronium in surgical patients. PMID- 1920804 TI - [The effect of drug therapy and stellate ganglion block with or without oxygen inhalation on sudden hearing loss]. AB - Forty-one patients suffering from sudden hearing loss were studied by the following method. Twenty patients (group A) were treated with oral administration of prednisolone, intravenous administration of vitamin B and C, furosemide and stellate ganglion block. Another 21 patients (group B) were treated with oral administration of these drugs, stellate ganglion block and oxygen inhalation. Forty six percent of all these patients, 35 percent of group A and 57 percent of group B, regained less than 20 dB of their normal hearing level. The patients who are younger, having shorter duration from first finding of symptoms to starting of therapy and smaller average deficiency of hearing, without dizziness are easy to recover. Oxygen inhalation with drug therapy and stellate ganglion block is a useful treatment for sudden hearing loss. PMID- 1920805 TI - [Iontophoretic administration of indomethacin in the treatment of postherpetic neuralgia]. AB - Iontophoretic administration of indomethacin (IND) was applied to investigate its effect in 21 cases of postherpetic neuralgia (PHN), which showed no response to other treatment such as nerve blocks. Iontophoretic therapy of IND was applied for 20 minutes once a week up to 5 time (series 1). When pain relief was unsatisfactory in series 1, the same treatment was given once again (series 2). Long term follow-up results were obtained 3 months after the final treatment in series 1 or 2. We used visual analog scale (VAS) to measure their pain intensity. VAS was reduced clearly at the end of the treatment in each series. The average improvement rate of the VAS in each series was as follows; series 1:60.3 +/- 8.2%, series 2:73.7 +/- 7.0%, long term follow-up results: 73.7 +/- 7.0% (mean +/ S.E.) We concluded from the present results that iontophoretic administration of IND was one of the effective and useful treatments for PHN. PMID- 1920806 TI - [Sevoflurane with continuous epidural anesthesia for removal of pheochromocytoma]. AB - A 66-year-old female was scheduled for right adrenalectomy because of a pheochromocytoma. Preoperative blood pressure was well controlled with an alpha.beta blocker, amosulalol hydrochloride 40 mg per day po for 2 weeks. The patient received midazolam 2.5 mg im and scopolamine 0.4 mg im 60 minutes before induction. Anesthesia was induced with midazolam 5 mg iv, fentanyl 0.1 mg iv and vecuronium 12 mg iv, and maintained with continuous epidural infusion of 1.5% lidocaine, and inhalation of 66% nitrous oxide in oxygen and sevoflurane (0.5 3%). Blood pressure was controlled with nicardipine (1-6 micrograms.kg-1.min-1) before removal of the pheochromocytoma. After removal of the tumor blood pressure was maintained with intravenous infusion of lactated Ringer's solution, dopamine (3-8 micrograms.kg-1.min-1), dobutamine (3-8 micrograms.kg-1.min-1) and norepinephrine (0.1-0.2 micrograms.kg-1.min-1). A combination of continuous epidural block and sevoflurane anesthesia was very useful for removal of the pheochromocytoma. Swan-Ganz catheter monitoring was also very useful before and during operation to determine the optimal doses of nicardipine, catecholamine and the volume of transfusion. PMID- 1920808 TI - [Antimicrobial activity of cefpiramide to fresh clinical isolates]. AB - In the subjects of 835 strains of 37 clinically isolated microbial strains, which were separated and identified among materials collected from patients with various infections and which were sent from medical therapeutic institutions throughout Japan in 1990, for the purpose of examining the antimicrobial activity of cefpiramide (CPM), its minimum inhibitory concentration (MIC), together with those of other cephem antibiotics, was determined, and the following conclusions were obtained. 1. Microbial strains in which no CPM-resistant strains emerged were Streptococcus pyogenes, Streptococcus pneumoniae and Anaerobic Gram-positive cocci. 2. In comparison with reports by many researchers at the former half of the 1980s, microbial stains suggesting an increase in resistance to CPM were Staphylococcus aureus, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas cepacia, Pseudomonas putida, Acinetobacter calcoaceticus, and Haemophilus influenzae, but also in other microbial strains the resistance to CPM was observed in high ratios. 3. Among strains used in the test, methicillin-resistant S. aureus, cephamycin and oxime type cephalosporin-resistant Gram-negative bacilli of Enterobacteriaceae, and new quinolone-resistant microbes were observed in high ratios; therefore, it was considered that CPM could not exert sufficient antimicrobial activities to these strains because of many resistant strains being complicated among these "CPM-resistant strains". 4. It was discussed that "the resistance mechanism observed throughout beta-lactam drugs as a while and the study themes in the dimension including social circumstances where resistant strains emerged", as pointed out by the authors in 1989, increased the significance of these days in the evaluation of timecourse changes in microbes resistant to specific drugs including CPM. 5. There are many unfavorable conditions in the antimicrobial activities of CPM to clinically isolated strains in recent years. However, it was jointly confirmed that CPM maintained effective antimicrobial activities to the majority of clinically isolated strains. Furthermore, when it was additionally considered that CPM was one of not many cephem drugs having persistent blood levels, a conclusion was drawn that CPM was one of clincally useful cephem drugs even at present. PMID- 1920807 TI - [Bacteriological study on fosfomycin against organisms clinically isolated from paranasal sinusitis]. AB - Multi-center bacteriological and clinical studies on fosfomycin (FOM) nasal solution were performed in subjects with paranasal sinusitis from January, 1988 to May, 1990. In these studies, we were exclusively responsible for bacterial isolation from clinical sources, bacterial identification and the determination of drug susceptibility. Before local administration of FOM nasal solution, many strains of various bacterial species were isolated from sources totalling 396 cases involved in phase II clinical studies, dose-finding and open clinical studies. From antibacterial activities of FOM against those isolates, we obtained the following conclusions. 1. Among the 447 isolates, Streptococcus spp. occupied 25.7%, Staphylococcus spp. 21.7% and anaerobic Gram-positive cocci (GPC) 13.6%, showing high detection frequency of aerobic and anaerobic GPC. Next to these, Haemophilus influenzae, Pseudomonas aeruginosa, Klebsiella spp. and Branhamella catarrhalis also were often obtained. 2. After exclusion of possibly contaminating strains which might have entered into cultures at samplings or transfers, the MIC50 and the MIC80 of FOM against the remaining 354 isolates were determined to be 12.5 and 25 micrograms/ml, respectively, indicating that local use of FOM would be fully effective to eradicate most of the bacteria. 3. FOM nasal solution showed sufficient eradication efficacy against most clinical isolates of possible causative organisms of paranasal sinusitis, and appeared to be useful as a topical preparation for the treatment of this disease. PMID- 1920809 TI - [Clinical evaluation of ciprofloxacin in pulmonary infections in the patients with chronic respiratory diseases]. AB - The clinical efficacy of ciprofloxacin (CPFX) was investigated in pulmonary infections in patients with chronic respiratory diseases. Out of 58 cases collected, 54 were evaluable for utility of CPFX including 20 with pneumonia, 34 with chronic bronchial infection. CPFX was given orally at 200 mg 3 times per day. In 20 cases of pneumonia, the mean age was 62.0 years underlying diseases were chronic bronchitis 9, bronchiectasis 6, inactive pulmonary tuberculosis 4, and diffuse panbronchiolitis 1. The efficacy rate of CPFX in this group was 90.0%. In 34 cases of chronic bronchial infection, the mean age was 59.8 years, underlying diseases included bronchiectasis 10, chronic bronchitis 8, inactive pulmonary tuberculosis 7, diffuse panbronchiolitis 5, and pulmonary emphysema 4. The efficacy rate of CPFX in this group was 70.6%. The overall efficacy rate in the entire cases was 77.8%, and we consider CPFX to be effective in the treatment of patients with chronic respiratory diseases. PMID- 1920810 TI - [Pharmacokinetics of netilmicin in patients after abdominal surgery]. AB - The pharmacokinetics of netilmicin (NTL) was examined in normal volunteers and patients after abdominal surgery who received a single administration of 100 mg, intramuscularly (i.m.) or intravenously (d.i.v.) over 30 or 60 minutes. In postoperative patients, the serum half life after i.m. or d.i.v. was increased, and absorption after i.m. was delayed compared to those in normal volunteers. No large differences between normal volunteers and postoperative patients were found in peak serum levels. The clearance of NTL from circulation was so rapid that the serum level decreased to below 1.0 micrograms/ml at 8 hours after administration. Renal functions were monitored after abdominal surgery in 116 patients who received NTL at a dose of 200 mg daily for 3-13 days by i.m. or d.i.v. Slight increases in serum creatinine were observed in only 2 patients after i.m., but not after d.i.v. From these results, intravenous infusion over 30 or 60 minutes of NTL seemed safe and effective for the prevention of postoperative infections after abdominal surgery. PMID- 1920811 TI - [A therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections in obstetrics and gynecology]. AB - Although it has been reported that the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections is extremely low in the obstetrics/gynecology setting, we recently had 5 patients with MRSA infections in the obstetrics/gynecology departments of 4 clinics in Yamagata Prefecture from September 1990 to February 1991. 1) Classified by disease, 4 of the patients had intrauterine infections (3 puerperal intrauterine infections and 1 intrauterine infection) and 1 had a postoperative wound infection. 2) Classified by treatment after the MRSA isolates had been determined, 2 of the patients were given imipenem/cilastatin alone (which turned out to be effective), 2 were given concomitant IPM/CS + quinolone agents (ofloxacin, tosufloxacin; effective) and 1 was given minocycline and OFLX. The principal lessons we learned from these cases are that attention should be paid to the occurrence of MRSA infection even in the obstetrics/gynecology field and that the method of selecting and administering antibiotics to prevent and treat such infections should be reconsidered. PMID- 1920812 TI - [A clinical phase I study on intramuscular imipenem/cilastatin sodium]. AB - The safety and pharmacokinetics of imipenem/cilastatin sodium (IPM/CS) were evaluated in comparative studies using single intramuscular injection, intravenous infusion or multiple intramuscular administration. The studies were done employing 30 healthy volunteers. Adverse effects were observed in 5 of 18 volunteers in the single intramuscular dose study. One of them complained of mild itching and mild pain at the injection site, and the other 4 volunteers had mild pain at the injection sites. With the other methods of administration, no adverse effects were observed. No other abnormal physical findings nor abnormal laboratory test values were observed in any of the studies. Imipenem (IPM) was absorbed rather slowly through the muscles, resulting in a low maximum plasma concentration (Cmax) and a prolonged half life (T1/2) upon intramuscular injection compared to the results obtained upon intravenous infusion. The total areas under the curves obtained with these 2 methods were similar, however. Cilastatin (CS) was absorbed rapidly after intramuscular injection, and the Cmax obtained was higher than that obtained for IPM. The T1/2 and the AUC of CS obtained with intramuscular injection were similar to those obtained with intravenous infusion. Cumulative urinary recovery rates obtained with these 2 different routes of administration were not different. Detectable urinary levels of IPM were maintained much longer upon intramuscular injection than upon intravenous infusion. In the multiple dose study, neither IPM nor CS showed tendency to accumulate. PMID- 1920813 TI - [Clinical evaluation of imipenem/cilastatin sodium in the internal medicine]. AB - Fifty-two patients with moderate or severe infections associated with internal medicine were treated with imipenem/cilastatin sodium (IPM/CS) and the efficacy and the safety of this drug were evaluated. There were 20 patients with pneumonia, 10 with acute exacerbation of chronic respiratory tract infections, 9 with sepsis, 2 with pyothorax, 3 with intraabdominal infection, 2 with urinary tract infection, 1 with pulmonary abscess, 1 with infective endocarditis, 4 with fever of unknown origin. Forty-four patients were evaluable for the efficacy. Clinical efficacies were excellent in 12 patients, good in 26, fair in 3 and poor in 3. The overall clinical efficacy was 86.4%. The efficacy rate was 63.6% in patients previously treated and 93.9% in patients previously untreated with other antibiotics. Bacteriologically, Staphylococcus aureus (8 strains), Streptococcus pneumoniae (5), Streptococcus pyogenes (1), other Gram-positive coccus (1), Klebsiella pneumoniae (8), Haemophilus influenzae (4), Pseudomonas aeruginosa (3), Serratia marcescens (3), Escherichia coli (3), Branhamella catarrhalis (1), Citrobacter freundii (1), Klebsiella oxytoca (1), Enterobacter sp. (1), and Peptostreptococcus sp. (1) were eradicated. P. aeruginosa (3) and Acinetobacter sp. (1) decreased. S. aureus (1), S. epidermidis (1), P. aeruginosa (5), and S. marcescens (1) persisted or appeared. The eradication rate was 83.7%. Six patients showed adverse reactions including general fatigue 1, epigastralgia 1, eruption 1, eosinophilia 1 and elevation of S-GOT 2. But all of the adverse reactions were mild or slight, and transient. These findings indicate that IPM/CS is a useful and safe drug against bacterial infections in internal medicine. PMID- 1920814 TI - [Clinical evaluation of imipenem/cilastatin sodium as a second line regimen in severe infections associated with hematologic disorders]. AB - Imipenem/cilastatin sodium (IPM/CS), which has a broad spectrum of activity against both Gram-positive and -negative bacteria including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, was used as the second choice for severe infections associated with hematological disorders. Sixty-five patients were treated with IPM/CS. Among them, 53 patients were evaluable for the clinical efficacy. Twelve patients were not evaluable due to the following reasons: 5 patients were treated with combinations of other regimens such as cefzonam, cefmenoxime, ciprofloxacin or gamma-globulin, 5 were patients to whom IPM/CS was administered as the first choice, and the remaining 2 patients were thought to be suffering not from febrile infections but from febrile tumor. Excellent responses were observed in 10 (18.9%) patients and good responses in 23 (43.4%) patients, with an overall rate of efficacy of 62.3%. The efficacy in septic patients was 75% (3/4), and that in patients whose peripheral granulocytes were continuously below 100/microliter was also 75% (6/8). Two patients who suffered from tumor fever and 5 patients who had received no chemotherapy before IPM/CS administration were included in the final evaluation of side effects. Side effects were observed in 16 patients (16/60, 26.7%). In a 61 years, female patient, a skin eruption was found 4 days after IPM/CS therapy was started. In 15 patients, mild gastrointestinal symptoms such as nausea and vomiting were identified within a few days after IPM/CS treatment was started. Abnormal laboratory data such as eosinophilia, liver dysfunction or renal dysfunction were also identified in 4 patients (4/60, 6.7%). Degrees of these abnormalities were very slight, however, and the continuation of treatment was not disturbed. These results indicated that IPM/CS was an effective second line regimen of chemotherapy for the treatment of severe infections in patients with hematological disorders. PMID- 1920815 TI - [Clinical evaluation of imipenem/cilastatin sodium against severe infections complicating hematological disorders and solid tumors]. AB - Imipenem/cilastatin sodium (IPM/CS) was administered to a total of 67 patients with severe infections complicating hematological disorders and solid tumors. Fifty patients are included in the present analysis of efficacy and 64 in that of safety. 1. Out of 31 patients with hematological disorders, responses were excellent in 10 patients, good in 10 patients, and the efficacy rate was 64.5%. Out of 19 patients with solid tumors, responses were excellent in 8 patients, good in 8 patients and the efficacy rate was 84.2%. 2. For patients whose responses to other antibiotics had been poor, the efficacy rate was 59.3% in the group with hematological disorders and 62.5% in the group with solid tumors. 3. The relationship between the neutrophil count and efficacy was studied in the patients with hematological disorders. The efficacy rate for 8 patients whose neutrophil counts were 500/mm3 or less was 75.0%. 4. For the patients with hematological disorders, the efficacy rate for patients from whom causative organisms were isolated was 70.0% and that for patients for whom they were unknown was 61.9%. 5. Adverse reactions were observed in 3 patients and abnormal laboratory test results in 2 patients. However, they were mild and disappeared after discontinuation of this drug. From these results, IPM/CS is considered to be a useful antibiotic for the treatment of severe infections complicating hematological disorders and solid tumors. PMID- 1920816 TI - Clinical effects of nitrendipine on variant angina pectoris. AB - The clinical effects of nitrendipine, a new calcium antagonist, were investigated in a single-blind test on 21 patients with variant angina pectoris. The efficacy of the drug was evaluated on the basis of frequency of anginal attacks and Holter electrocardiographic findings during different treatment periods at doses of 10 mg once a day (period I) and 20 mg once a day (period II). The number of anginal attacks decreased significantly from a pretreatment level of 2.1 +/- 0.3 per day to 0.7 +/- 0.2 per day in treatment period I and 0.3 +/- 0.1 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The consumption of sublingual nitroglycerin tablets decreased significantly in both treatment periods in comparison with the observation period before treatment (p less than 0.01, p less than 0.001, respectively). In 20 patients with continuous ECG monitoring, the frequency of ST-segment elevation was 4.5 +/- 1.0 per day during the pretreatment period; it decreased significantly to 0.9 +/- 0.6 per day in treatment period I and 0.5 +/- 0.3 per day in treatment period II (p less than 0.01, p less than 0.001, respectively). The duration and the maximum magnitude of ST-segment elevation also improved significantly in both treatment periods. These results demonstrate the efficacy of nitrendipine in the treatment of variant angina at a single daily dose of 10 mg. PMID- 1920817 TI - Ketanserin and hydrochlorothiazide in the treatment of arterial hypertension. AB - The chronic antihypertensive effect of the combination of ketanserin (KET) 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg was evaluated in 20 patients with arterial hypertension of mild to moderate degree. After a 2-week wash-out period, patients were prescribed a single oral dose of KET 40 mg or HCTZ 25 mg in a randomized order at 2-day intervals and blood pressure and heart rate were measured during the following 24 hrs by an automatic recorder. Thereafter patients were given the combination of KET 40 mg + HCTZ 12.5 mg for 6 weeks and 24 hrs blood pressure was recorded after the first dose of the combination and at the end of treatment. Ketanserin induced a significant fall in systolic and diastolic pressures for up to 8 hrs; thiazide did not induce any change in these parameters. The combination of KET + HCTZ in the acute study reduced significantly systolic (SBP) and diastolic (DBP) blood pressures for up to 10 hrs. After 6 weeks of treatment with KET + HCTZ, blood pressure showed a further fall at each time period and was normalized (BP greater than 160/80 mmHg) for 8 hrs after dosing. The results of this study indicate that once daily oral administration of the combination of KET 40 mg + HCTZ 12.5 mg in mild to moderate primary hypertensives significantly reduces blood pressure over 24 hrs. Fairly good control of BP, i.e. BP less than 160/90 mmHg, was, however, achieved only up to 8 hrs after drug administration, indicating that this combination given once daily is not able to normalize BP over the following 24 hrs. PMID- 1920819 TI - Types of division of the left coronary artery and the ramus diagonalis of the human heart. AB - The surgical, clinical and radiological importance of the diagonal artery in the human heart and the extreme variability in its description prompted us to undertake its study. The investigation was performed in 150 hearts, dissected after injection of colored substance in the coronary arteries. The following results were obtained: The left coronary artery presented 3 types of division: bifurcation (54.7%), trifurcation (38.7%) and quadrifurcation (6.7%); the latter 2 patterns produced a diagonal artery. The trunk of the left coronary artery bifurcated more frequently in hearts of female Caucasians (57.1%) and male Caucasians (54.9%). It trifurcated more frequently (60%) in hearts of female non Caucasians. The ramus diagonalis was found in 45.3% of the hearts. The incidence of a ramus diagonalis did not differ significantly between male Caucasians (45%), male non-Caucasians (42.8%) and female Caucasians (37%). However, it occurred more frequently in female non-Caucasians (66.5%). The length of the ramus diagonalis varied from 20.1 to 50 mm (79.3%) and its relative length varied from 21 to 50% of the length of the left ventricle (75.3%). The ramus diagonalis was classified as short, medium and long types, the former 2 types were most frequent. PMID- 1920818 TI - Acute pericarditis: etiology, treatment and prognosis. A study of 115 patients. AB - One hundred and 15 hospitalized patients with acute pericarditis were analyzed retrospectively for their etiology, management and long-term prognosis. It was found that most of the patients had either idiopathic or viral etiologies (60%), collagen disease (16.4%) or malignancy (6.9%). Most of the patients were treated with non-steroidal anti-inflammatory drugs (NSAID). Twenty-six patients (22%) required corticosteroids following NSAID treatment failure. Only one patient underwent pericardiocentesis for tuberculous pericarditis. The long-term prognosis was good, although 21.9% of the patients suffered from recurrent episodes of pericarditis. It is concluded that in hospitalized patients with pericarditis, an extensive workup may not reveal the major etiologies, and the disease may be more complicated than previously thought. PMID- 1920820 TI - Non-linear pressure-volume relation in left ventricle. AB - A thick-walled elastic cylinder contracting symmetrically is used as a model for the myocardium. The active force generated by the myocardium during systolic contraction is represented by body force (force/unit volume of myocardium). A mathematical formalism previously developed and based on large deformation analysis is used to derive a quadratic equation to represent the non-linear pressure volume (P-V) relation in the left ventricle in the Suga-Sagawa model. Experimental application of the results obtained confirms the consistency of the mathematical formalism developed to describe the P-V curve in the Suga-Sagawa model. PMID- 1920821 TI - Chronic effects of tolbutamide on myocardial tension during ischemia and reperfusion in perfused hearts isolated from insulin dependent and non insulin dependent diabetic rats. AB - The chronic effects of tolbutamide on myocardial contractility of the diabetic heart during ischemia and reperfusion were evaluated in perfused, isolated rat hearts. Five experimental groups were used: (1) control rats (C), (2) insulin dependent diabetic rats (IDDM, single intravenous injection of 60 mg/kg streptozotocin (STZ) in male Sprague-Dawley rats), (3) non insulin dependent diabetic rats (NIDDM; single subcutaneous injection of 90 mg/kg STZ in 5 day neonates), (4) tolbutamide-treated IDDM and (5) NIDDM (T-IDDM, T-NIDDM; giving tolbutamide 100 mg/kg/day for 6 weeks via an orogastric tube every day, respectively). At 14 weeks of age, experiments were performed using a Langendorff perfused heart preparation. After equilibration, T (myocardial developed tension), +dT/dt (contraction velocity), -dT/dt (relaxation velocity) and RT (resting tension) were measured during a 15 min period of global ischemia, followed by reperfusion for 20 min. Basal values of T increased in both T-IDDM and T-NIDDM, compared to IDDM and NIDDM, respectively. The percent recovery rate of +dT/dt in T-IDDM increased significantly during both ischemia and reperfusion, but the change in T-NIDDM was not significant. The recovery rates of -dT/dt in T IDDM and T-NIDDM were significantly higher throughout reperfusion than in IDDM and NIDDM, respectively. On the other hand, that of T in T-IDDM and T-NIDDM were significantly higher than IDDM and NIDDM throughout ischemia and reperfusion, respectively. The RT was significantly higher in IDDM than in C and NIDDM throughout ischemia and reperfusion. The RT was significantly lower during ischemia in IDDM, but it did not differ significantly from IDDM during reperfusion. These results indicate that chronic oral administration of tolbutamide directly improved myocardial contractility throughout ischemia and reperfusion regardless of the improvement of glycemia. The improvement was also greater in IDDM than in NIDDM. PMID- 1920822 TI - Effects of hypoxia and reoxygenation on regular contractions and postrest contraction in rat papillary muscles. AB - The effects of hypoxia and reoxygenation on regular contractions and postrest contractions (PRC) of papillary muscle of rats were studied. Isometric tension was measured during two cycles of hypoxia and reoxygenation. Trains of 80 externally continuous stimulations at 40/min were applied. PRCs were evoked by a stimulus train after a 60 sec resting interval. After 90 min of hypoxia (the first hypoxia period), regular contractions and PRCs decreased to 5.6 +/- 2.0% and 23.4 +/- 2.4% of baseline values, respectively (p less than 0.001; n = 18). After 90 min of reoxygenation, the recovery of the PRCs (44.4 +/- 3.4%) was better than that of the regular contractions (23.3 +/- 3.3%) (p less than 0.01; n = 18). After 30 min of hypoxia (the second hypoxic period), regular contractions and PRCs decreased to 2.2 +/- 0.6% and 13.6 +/- 1.6% of baseline values, respectively (p less than 0.001; n = 18). However, the recovery from the second hypoxic injury was not significant for either regular contractions or PRCs. The % diastolic tension, which was normalized to the baseline for regular contractions, increased to 113.2 +/- 6.9% and 133.6 +/- 8.4% at the end of the first and the second hypoxic periods, respectively. There was statistically significant correlation between the % diastolic tension and the % hypoxic injury of PRCs (p less than 0.002; n = 18). There was no significant relationship between % diastolic tension and % hypoxic injury of regular contractions. There was no statistically significant correlation between % diastolic tension and % recovery from the hypoxic injury of either regular contractions or PRCs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920823 TI - Changes in myocardial electrolytes and ventricular fibrillation threshold induced by alcohol feeding in laboratory rats. AB - Three groups of rats were studied in an investigation to determine the influence of alcohol on myocardial electrolytes and the ventricular fibrillation threshold (VFT) levels. Drinking water was provided ad libitum; the control group received water while the other 2 groups drank a water-ethanol solution, constituted in a ratio of 75: 25, for periods of 3 and 9 months, respectively. Two rats from each of the experimental groups, together with a control rat were killed on each experimental day. One heart was studied on the Langendorff preparation and the other used for tissue electrolyte analysis. The mean myocardial Mg2+ levels (233 +/- 28 micrograms/g vs 148 +/- 23 micrograms/g and 233 +/- 28 micrograms/g vs 107 +/- 15 micrograms/g; p less than 0.0001), K+ levels (3260 +/- 437 micrograms/g vs 1779 +/- 312 micrograms/g and 3260 +/- 437 micrograms/g vs 1195 +/- 205 micrograms/g; p less than 0.0001) and Zn2+ levels (32.7 +/- 6.8 micrograms/g vs 14.0 +/- 4 micrograms/g and 32.7 +/- 6.8 micrograms/g vs 4.2 +/- 3.4 micrograms/g; p less than 0.0001) were significantly lower in alcohol fed rats than the controls. In addition, a significant fall in the mean VFT levels (10.1 +/- 1.94 mA vs 6.27 +/- 2.17 mA, p less than 0.001) was noted in rats given water: alcohol solution for 9 months. This study reveals that chronic exposure to alcohol induces a deficiency of myocardial Mg2+, K+ and Zn2+, and an increase in myocardial irritability in laboratory rats. PMID- 1920824 TI - Indomethacin treatment in newborn canine endotoxic shock. AB - Prostaglandins have been reported to play an important role in endotoxic shock. However, the beneficial effects of prostaglandin synthesis inhibitors for the treatment of newborn endotoxic shock have been controversial. This study was performed to evaluate the effects of indomethacin on the hemodynamics during fulminant endotoxic shock in newborn dogs. After E. coli lipopolysaccharide (LPS) injection, mean arterial pressure was maintained for the first 60 min, and then declined from 53 +/- 2 to 27 +/- 2 mmHg at 120 min. Cardiac output dropped from 0.37 +/- 0.03 to 0.24 +/- 0.03 L/min/kg 5 min after LPS injection and continued to decline to 0.12 +/- 0.01 L/min/kg at 120 min. Indomethacin treatment 20 min prior to LPS injection attenuated the hypotension (50 +/- 3 mmHg at 120 min, p less than 0.05) and the decrease of cardiac output (0.18 +/- 0.02 L/min/kg at 120 min, p less than 0.05). Indomethacin treatment 5 min after LPS injection also attenuated the hypotension (55 +/- 4 mmHg at 120 min, p less than 0.05) and the decrease of cardiac output (0.21 +/- 0.02 L/min/kg at 120 min, p less than 0.05). Survival times were increased by the indomethacin treatments. Thus, indomethacin appears to be beneficial for the treatment of fulminant hemodynamic deterioration in newborn endotoxic shock. PMID- 1920825 TI - Cardiac rhabdomyoma in a newborn two-dimensional echocardiographic diagnosis. AB - Primary cardiac tumors are quite rare in the newborn period. Prior to surgery, cardiac catheterization and angiocardiography have been performed to confirm the two-dimensional echocardiographic findings. In this report a 2-day-old baby with the clinical impression of severe cyanotic congenital heart disease diagnosed by two-dimensional echocardiography as multiple rhabdomyoma and confirmed by surgery is presented. It is emphasized that two-dimensional echocardiography is a very useful technique for the diagnosis of primary cardiac tumors. By means of this method severely symptomatic newborns may be taken directly to surgery without prior cardiac catheterization, thus minimizing complications. PMID- 1920826 TI - Extracardiac malignancy presenting as cardiac tamponade. AB - Two cases of extracardiac malignancies presenting with cardiac tamponade are reported. One patient had adenosquamous carcinoma of the lung. Such a manifestation of this tumor has never been reported previously. The second patient had an adenocarcinoma and is the youngest case of carcinoma presenting with tamponade. The English literature has been reviewed. PMID- 1920827 TI - Arrhythmia development in a young subject with right ventricular cardiomyopathy (right ventricular dysplasia). AB - In right ventricular cardiomyopathy the relationship between the progression of structural abnormalities and arrhythmia development is not yet well known. This report describes a case in which severe ventricular arrhythmias appeared 3 years after the demonstration of right ventricular (RV) structural and dynamic abnormalities. In this interval of time structural changes were not detectable with the commonly used diagnostic methods, but endocavitary RV late fractionated QRS potentials appeared suggesting the development of an arrhythmic component of the disease. PMID- 1920828 TI - Native valve bacterial endocarditis due to Staphylococcus epidermidis. A community acquired infection following an acute course. AB - Staphylococcus epidermidis (SE) is the leading pathogen of prosthetic valve endocarditis. At the same time it is a very rare cause of native valve endocarditis and it follows a clinical course and outcome similar to Streptococcal viridans endocarditis. We report here the case of a 41-year-old man with a community acquired SE endocarditis of a native aortic valve. Despite early surgical intervention, the case followed an acute and fatal course. PMID- 1920829 TI - Two-dimensional echocardiographic findings in postoperative aortic suture line endarteritis. AB - Infections occurring after aortic valve surgery, whether valvuloplasty or replacement, commonly affect the valve itself. However infection of the aortic suture line alone is extremely rare. Such cases with endarteritis can be diagnosed at autopsy or by angiocardiography. In this report a patient with a vegetation at the aortic suture line which was diagnosed by echocardiography is presented. By two-dimensional echocardiography, a very mobile and echo-dense mass protruding from the ascending aorta was observed on the recordings through the suprasternal notch. This diagnosis was surgically confirmed and the patient was treated. PMID- 1920830 TI - [The relation of protein kinase activities and the leukemic cell growth]. PMID- 1920832 TI - [Cases of drug-induced blood disorders in Chugoku district]. AB - 23 cases of drug-induced blood disorders were reported from 7 hospitals in Chugoku district. These cases were treated between Oct 1982 and Jun 1990. These included 5 cases of anemia, 2 cases of leukopenia, 6 cases of thrombocytopenia, 1 case of anemia and leukopenia, 2 cases of anemia and thrombocytopenia, and 1 case of leukopenia and thrombocytopenia. There was a case of methemoglobinemia due to Sedes-G. A patient of agranulocytosis due to cimetidine died of sepsis. The all other patients recovered. The reported drugs which induced blood disorders were analgesics, anticonvulsant agent, chemotherapeutic agent, antituberculosis agent, and H2 receptor blockade, etc. in order of number. The drugs in 3 cases were definitely thought to be the cause of blood disorders, probably in 18 cases, and possibly in 2 cases. PMID- 1920831 TI - [Drug-induced hematologic disorders in Shikoku district]. AB - The case survey of drug-induced hematologic disorders in Shikoku District (Ehime Prefecture) disclosed 21 patients. Cases were 12 rheumatoid arthritis patients, 2 brain tumor, one epilepsy, 2 liver cirrhosis, one neuralgia, one arthralgia, one hyperthyroidism, and one IBL-like T-lymphoma. Causative drugs for aplastic anemia were Metalcaptase, Shiosol, Voltaren and Emeside. Drug-induced aplastic anemia was so severe that 4 out of 5 patients had died of bone marrow dysfunction. Neutropenia was caused by drugs as Rimatil, Cefobit, Sepatren, Mercazole, Sulpyrin, Aleviatin, Cefamedin and Metalcaptase. The real causes of these drug induced hematologic disorders have not been clear. Remarkably high incidence among rheumatoid arthritis patients is suggestive several reasons as unique reactivity associated with HLA, suppression on hematologic stem cells by abnormal metabolites, and immunologic dysfunction commonly seen in collagen diseases. Further studies of more accurate incidence of drug-induced hematologic disorders are needed in investigating real causes of unhappy side-effects. PMID- 1920833 TI - [Drug-induced blood dyscrasia in Kinki district]. AB - Thirty-six cases of drug-induced blood dyscrasias were collected in Kinki District. They were consisted of 14 agranulocytosis, 9 agranulocytosis with anemia, 7 pancytopenia, 2 anemia (hemolytic anemia and pure red cell aplasia), 2 thrombocytopenia and 2 agranulocytosis with thrombocytopenia. The causative agents were 10 antibiotics, 10 cardiovascular drugs, 5 anti-rheumatic drugs, 3 antithyroid drugs and 3 anticonvulsants. Six patients with advanced age died from sepsis within 14 days after the onset of agranulocytosis. PMID- 1920834 TI - [Drug induced blood dyscrasis in the Kanto district]. AB - Ten years experience of 14 hospitals in Kanto district with drug induced blood dyscrasia (DBD) were reviewed. There were 78 patients, male/female ratio was 1:1, and cases more than 80 years old were 10.3%. It was very difficult to identify the causative agents, and only 8 cases were definitive. After disease 9 case were died, and DBD prolonged more than 50 days from onset in 8 patients. Thirty-one patients (39.7%) were due to Antibiotics, beta-lactam were most frequent, 12 cases were due to analgesics, 5 patients were due to thiamazole. In order to elucidate the incidence of DBD, studies had carried out concerning antibiotics and H2 receptor antagonists (H2RA). DBD due to antibiotics increased from 0.5% in 1981 to 4.2% in 1982, because medication of third-generation cephalosporins was began to use. In 109 outpatients with H2RA, there was no DBD, but in 54 hospitalized patients DBD were found in 3.6%. DBD might be more frequent in fact. It is necessary to start big study and to develop new technique for confirmation. PMID- 1920835 TI - [Drug-induced blood dyscrasias in Tohoku district]. AB - One hundred and thirty-four cases were identified in seven prefectures of the Tohoku district. Fifty-seven per cent of them were over 50 years old, and the incidence had no differences between sexes. They consisted of 51 leukopenia, 32 thrombocytopenia, and nine anemia cases which included seven hemolytic anemia and two pure red cell aplasia. Agents associated with blood dyscrasias were those acting on the central nervous system (CNS) (49 cases), cardiovascular drugs (25 cases), and antimicrobial agents (48 cases). Leukopenia occurred to five patients with cinepazidemaleate (Brendil) administration, 11 with thiamazole (Mercazole), and 14 with antimicrobial agents which were mainly penicillins and cephalosporins. Thrombocytopenia was induced by H2-receptor antagonists (six cases) and antimicrobial agents mostly of penicillins and cephalosporins (12 cases). Anemia contained seven cases of hemolytic anemia, including two patients caused by methyldopa (Aldomet) and two by dried human immunoglobulin (Glovenin). Among 15 cases, 12 out of 19 agents were those affecting the CNS. Six cases were dead from drug-induced blood dyscrasia. PMID- 1920836 TI - [An investigation of drug-induced hematologic disorders in Japan--result of Hokkaido]. AB - Patients with drug-induced hematologic disorders were clinically analysed. Fifty nine cases were registered from 6 hospitals in Hokkaido. These were 21 cases of male and 38 of female. Age-distribution was 18 to 84 years old. Types of hematologic disorders were as follows, 9 cases of pancytopenia, 16 of bicytopenia and 31 of monocytopenia. Leukocytopenia only and leukocytopenia with another disorders were high incidence (85%). Decision of causal drug are done by DLST (drug lymphocyte stimulation test); 5 cases, drug-rechallenge; 3 cases and clinical course only; 31 cases. In 11 fatal cases by this lesion, there included 7 cases of pancytopenia. PMID- 1920837 TI - [Long-term oral administration of etoposide (VP-16) for the patients with refractory or relapsed acute non-lymphocytic leukemia]. AB - We investigated the efficacy of oral etoposide (VP-16) for the patients with acute non-lymphocytic leukemia (ANLL) in relapse or refractory to the standard chemotherapy. Patients were given etoposide orally at the dose of 50 mg/body/day on consecutive days until the leukemic cells in the bone marrow were reduced less than 5%. The duration of administration of oral etoposide ranged from 16 days to 50 days (average 30 days). Seven patients were given very low dose cytosine arabinoside (5 approximately 10 mg X 2/day i.s.c.) combination with oral etoposide. Six patients (66.7%) out of 9 achieved complete remission (CR) and 3 patients had no response. Adverse effects such as abdominal discomfort and appetite loss were observed in 3 patients, but they were mild and tolerable. The duration of CR ranged from 2 to 24 (+) months, and the median CR duration is 7 months. The over all CR rate (66.7%) in this group of patients with refractory or relapsed ANLL were encouraging. Further studies, however, are needed to evaluate the efficacy of long term oral administration of etoposide for the patients with leukemia. PMID- 1920838 TI - [Clinical and cytological features of acute myelogenous leukemia with 8; 21 chromosome translocation]. AB - Eight cases of acute myelogenous leukemia with (8; 21) translocation were reported. As recently reported, they showed following features: M2 morphology in FAB classification (all 8 patients), abnormal granulocyte maturation, i.e. large granules and pseudo Pelger-Huet forms (5), Auer rods (8), occasional eosinophilia (2), frequent loss of one sex chromosome (5), the low neutrophil alkaline phosphatase activity (5), and tumor formation (one). Both CD13 and CD33 antigens were expressed on smaller number of leukemic cells than the other AML (M2) cells, whereas CD34 and HLA-DR antigens were expressed on higher number of cells. Interestingly CD19 antigen was detected on a small to large population of tumor cells from four out of six patients. Despite the high remission rate, many of them relapsed within one year. More intensive postinduction and maintenance therapy should be considered for those patients. PMID- 1920840 TI - [Elevated plasma interleukin-6 in patient with idiopathic thrombocytopenic purpura]. AB - Plasma Interleukin-6 (IL-6) level was measured in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), rheumatoid arthritis and aplastic anemia. Increase in the plasma level of IL-6 was observed in patients with ITP and SLE. The plasma IL-6 level decreased with progression of the treatment for ITP, and it showed weak negative correlations with the platelet count at the onset of ITP. The increases in the plasma IL-6 level suggest the involvement of activation of the immune system in the pathogenesis of ITP. PMID- 1920839 TI - [Cytogenetic studies on 53 childhood acute nonlymphocytic leukemia]. AB - Cytogenetic study in 53 children (aged less than 15 years) with acute non lymphocytic leukemia (ANLL) were studied. The cytogenetic findings were compared with those of ANLL patients (136 aged less than 19 years and 747 aged over 20 years) in the Fourth International Workshop on Chromosomes in Leukemia (IV IWCL) and also with those of childhood acute lymphoblastic leukemia (ALL) cases (previously reported as our 124 ALL case). Of the ANLL patients, 77.4% had acquired chromosomal clonal abnormalities. As abnormalities, t(15;17), all cases which were seen in M3 or M3V cases, t(8;21), which was seen in M1 or M2, and rearrangements of 11q23, which were seen in M5, were more frequently seen than was reported at the IV IWCL (20.8%, 17.0% and 7.5% vs 6.3%, 6.3% and 3.2% respectively). 5q-, monosomy 7, t(6;9) and t(9;22), which have been noted previously in this disease, were not seen. Besides structural abnormalities, some cytogenetic differences in numerical abnormality between ALL and ANLL were observed as follows: 1) Hyperdiploidy of greater than 51 chromosomes noted in ALL was not found in ANLL. 2) Isolated trisomy 8 was frequently found in ANLL, but not in ALL. 3) Loss of a sex chromosome was frequently found in ANLL, but not in ALL. Our study revealed a different frequency of non-random chromosome abnormality in children with ANLL as compared with that of adults, and clarified the differences in numerical abnormalities, as well as structural abnormalities, between ALL and ANLL. PMID- 1920841 TI - [A case of adult T-cell leukemia with a defective HTLV-I proviral DNA, in which the single T-cell clone appeared to have progressed from chronic phase to crisis]. AB - A 39-year-old woman was first admitted to our hospital with increased white cell count on May, 1983. Physical examination showed only mild splenomegaly. Hematological examination revealed leukocytosis (14,600/microliters) with ATL cells (59%). Serum anti-HTLV-I antibody was positive. Examination of HTLV-I provirus in the abnormal T cells revealed the defective type. She was diagnosed as chronic type of ATL based on the clinical features. Cytogenetic study of the ATL cells revealed 47, xx, +4. For 12 months, she was followed without any therapy. WBC reduced to almost normal range and ATL cells decreased to 3 to 6% for 8 months. On May, 1985, she was readmitted to our hospital because of leukocytosis (32,200/microliters), and increased ATL cells (57%). She was diagnosed as crisis of ATL. Investigation of the proviral DNA and chromosome showed the same results as those of the chronic phase, indicating that ATL cells in both the chronic phase and the crisis phase originated from the same clone. She died after 3 months from massive diarrhea. Postmortem examination showed the extensive infiltration of leukemic cell in the small intestine. PMID- 1920842 TI - [An 8; 21 chromosome translocation associated leukemia presenting with large intestinal granulocytic sarcoma: a report of two cases]. AB - Two patients of acute myelogenous leukemia (AML) presented with a large intestinal tumor and related symptoms. They had a tumor in the rectum or the ascending colon. Bone marrow cells obtained from both patients showed a karyotype with t(8;21). Chromosomal findings in the former patient has already been reported in detail (Am J Hematol 4, 273, 1978). These findings and reports in the literature indicate that large intestinal tumor may not be rare in AML with an 8;21 translocation. Complete remission was achieved after chemotherapy, when their intestinal tumors disappeared. PMID- 1920843 TI - [Chronic myelocytic leukemia induced into remission by interferon-alpha associated with early esophageal cancer]. AB - A fifty-one-year-old male patient visited the Department of Dermatology of Toho University Ohashi Hospital with a complaint of generalized exanthema, which was diagnosed assyringoma; at that time his leukocytosis was recognized. He was admitted to our department on August 8, 1988. Physical examination on admission revealed slight hepatosplenomegaly. WBC count was elevated (50,700/microliters). He was diagnosed as having Ph1-positive CML in the chronic phase and was treated with IFN-alpha (HLBI, Sumitomo, 3 x 10(6) units/day, daily, I. M.) from August 12, but an elevated lesion was detected at the lower part of his esophagus by endoscopy, and it was diagnosed by biopsy as squamous cell carcinoma. Radical operation for esophageal cancer was performed on September 26; at that time his WBC count was 17,400/microliters. After discharge, his WBC level was maintained within normal range by IFN-alpha. On August 2, 1989, he was readmitted to our hospital because of lymphoblastic crisis. Although he attained transient complete remission, he died of pneumonia after the relapse on January 10, 1990. IFN-alpha therapy is suggested to be useful for the treatment of CML associated with gastrointestinal cancer because of its possible parenteral administration and mild toxicity. PMID- 1920844 TI - [Treatment of iron overload with combination of recombinant human erythropoietin and phlebotomy]. AB - A patient of Coombs negative autoimmune hemolytic anemia was massively transfused of 162 units concentrated red blood cells in 3 months and developed iron overload disease which was confirmed by liver biopsy. Hemolysis was successfully treated with high-dose methyl-prednisolone therapy and splenectomy. To treat iron overload, we administered recombinant human erythropoietin (Epo) in combination with phlebotomy. Total iron removed for 5 months was about 4 g. Thus, combination of Epo and phlebotomy was effective for the treatment of iron overload disease. Furthermore, we compared a degree of clinical effect of subcutaneous administration of Epo with that of intravenous administration in the clinical course and found the former more effective. PMID- 1920845 TI - [Acute renal failure due to endocapillary proliferative glomerulonephritis in a patient with IBL-like T-cell lymphoma]. AB - A 72-year-old man was admitted of generalized lymphadenopathy and oliguria on December 12, 1987. Laboratory findings revealed progressive renal impairment, polyclonal hypergammaglobulinemia, and reduction of serum complements. A cervical lymph node was typically suitable for histology of IBL-like T-cell lymphoma. The surface markers of lymph node were mainly CD2 (+) and CD3 (+) and clonal proliferation of lymphoma cells was proved by TCR-beta gene rearrangement. Renal biopsy to examine the pathogenesis of acute renal failure revealed endocapillary proliferative glomerulonephritis without invasion of lymphoma cells. Both lymphadenopathy and renal failure were improved by successful administration of prednisolone and hemodialysis. Although relapsed tumor was partially responded to vincristine and prednisolone, he died of alimentary tract bleeding. We reported a case of IBL-like T-cell lymphoma with acute renal failure due to endocapillary proliferative glomerulonephritis. PMID- 1920846 TI - [Drug therapy manual (2)--basis of drug administration and therapeutic programs]. PMID- 1920847 TI - [Organ transplantation and clinical tests]. PMID- 1920848 TI - [Immunosuppressive therapy]. PMID- 1920849 TI - [Infection and protected environment]. PMID- 1920851 TI - [Renal transplantation]. PMID- 1920850 TI - [Blood transfusion and transplantation]. PMID- 1920852 TI - [Bone marrow transplantation]. PMID- 1920853 TI - [Liver transplantation]. PMID- 1920854 TI - [Transplantation immunology]. PMID- 1920855 TI - [Heart transplantation]. PMID- 1920856 TI - [Pancreas transplantation]. PMID- 1920857 TI - [Lung transplantation]. PMID- 1920858 TI - [Pathology of renal allograft]. PMID- 1920859 TI - [Plasma factor VII levels in disseminated intravascular coagulation]. AB - To evaluate the activation of the extrinsic pathway of coagulation in disseminated intravascular coagulation (DIC), plasma factor VII coagulant activity (FVIIc) and antigen levels (FVIIag) were measured in 81 blood samples obtained from the 56 patients with DIC together with various hemostatic parameters. Plasma FVIIc (77 +/- 40%, range: 11-200%) and FVIIag (76 +/- 43%, range: 16-175%) were significantly lower in DIC subjects than in age-matched controls (FVIIc: 128 +/- 28%, FVII: 128 +/- 31%, p less than 0.01) and correlated significantly with both the antithrombin III and plasminogen activities (p less than 0.001). These results indicated that a decrease in factor VII levels is due to the consumption. However, there were several exceptions which showed elevated factor VII levels. This seems to be due to enhanced liver synthesis of factor VII compensating for the consumption. The level of tPA-PAI-I complex, a marker of pathologic endothelial stimulation, was negatively correlated with FVIIag (r = 0.45, p less than 0.05). Thus, the more the endothelium is pathologically stimulated, the more the extrinsic pathway is activated in DIC. The FVIIc/FVIIag ratio, an index of activation of factor VII zymogen, correlated with FDP and fibrin monomer levels (p less than 0.01). There were no correlations between the thrombin-antithrombin III complex. D-dimer, and alpha 2 antiplasmin-plasmin complex levels and factor VII levels. Considering the underlying diseases. the FVIIc and FVIIag levels were markedly lower in liver cirrhosis, but not significantly different in other diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920860 TI - [Fibrin monomer assay]. AB - Quantitative assay for fibrin monomer was done by use of a chromogenic substrate (S-2390, Coa set fibrin monomer). Samples from DIC prone patients with the underlying disease were assayed and classified into four groups. The pre DIC group showed higher FM values than the control with no laboratory coagulation abnormality, although the FDP . D-dimer showed no significant rise. FM assay is a useful marker for the detection of early coagulopathy in DIC. Administration of the AT III concentrate in the case of low level of plasma ATIII, thrombin . antithrombin complex I (TAT) caused a significant transient rise. The clinical course of DIC by TAT is often affected by the fluctuation of ATIII level in plasma, the usefulness of FM is that it reflects the real thrombin generation in DIC. PMID- 1920861 TI - [Clinical usefulness of the measurement of plasma D-dimer levels]. AB - To evaluate the clinical usefulness of D-dimer, various effects on the measurement of D-dimer were examined. Although both fibrinolytic and fibrinogenolytic products were detected by the measurement of FDP, only fibrinolytic products were detected by the measurement of D-dimer. In patients with DIC and other thrombo-embolic diseases, plasma D-dimer levels were significantly higher than in normal persons. A significant positive correlation between plasma D-dimer and serum FDP was found in DIC patients. In patients with DIC associated with acute promyelocytic leukemia, which is thought to be an increased fibrinogenolysis state, serum FDP was higher than the plasma D-dimer which suggests that increased fibrinogenolysis affects the result of serum FDP measurement. Plasma D-dimer significantly increased 5 minutes after endoscopic embolization with thrombin in the patients with esophageal varices. However serum FDP increased 30 minutes after the treatment, which suggests that the D-dimer is more useful for rapid detection of coagulo-fibrinolytic change than serum FDP. Plasma D-dimer was significantly higher in patients with cerebral infarction and increased with age. These finding suggest the usefulness of plasma D-dimer measurement for the specific and rapid evaluation of coagulo-fibrinolytic activation and thrombo-embolic state. PMID- 1920862 TI - [Thrombin.antithrombin III complex]. AB - Increase of TAT is reflected by the generation of thrombin in hypercoagulable state. TAT might increase in DIC characterized by the formation of disseminated micro-thrombosis. DIC was classified into three groups according to the results of screening tests (FDP, platelet count, fibrinogen, prothrombin time). TAT values significantly increased in the stage of pre-DIC compared with the control group consisting of DIC prone underlying disease. Pre-DIC was easily detected by an increase of TAT during the clinical course. Management of high TAT began with the use of an anticoagulant such as heparin under the condition of sufficient ATIII level. The lowering effect of TAT was easily obtained by the anticoagulant. In ATIII-deficient DIC, the high TAT reduced with the substitution of ATIII concentrate, though a transient increase of TAT was found during the administration of ATIII. To reduce the high TAT under the deficient state of ATIII, MD805, a synthetic thrombin inhibitor, was introduced to avoid further consumption of ATIII. The TAT was decreased by the use of MD805 without administration of ATIII. MD805 could be used as an effective anticoagulant in high TAT due to DIC under an ATIII-deficient state. Although the TAT improved with an adequate anticoagulation in DIC, spontaneous bleeding sometimes appeared as a complication associated with the high level of alpha 2 plasmin inhibitor plasmin complex. In this case, the combined use of tranexamic acid relieved the bleeding. PMID- 1920863 TI - [Factor XIa-alpha 1 antitrypsin complex]. AB - We developed a new rapid assay for the factor XIa-alpha 1 antitrypsin complex (FXIa-alpha 1AT) in plasma using an anti FXI monoclonal antibody (KMXI-1). In 20 fold diluted plasma samples, this assay was not affected by co-existing FXI or non specific color development of the plasma. Normal level of FXIa-alpha 1AT (11 +/- 4.1 ng/ml plasma) increased with the aging of healthy adults. The FXIa-alpha 1AT levels of patients with disseminated intravascular coagulation (DIC) rose along with the progression of the disease, and the appearance of high levels and the peak of FXIa-alpha 1AT developed faster than FDP-E or alpha 2plasmin inhibitor-plasmin complex (alpha 2PI-PmC) in most patients. These results indicate that, in addition of FDP and alpha 2PI-PmC, FXIa-alpha 1AT is a useful molecular marker for DIC. PMID- 1920864 TI - [Levels of tissue-type plasminogen activator and plasminogen activator inhibitor 1 in disseminated intravascular coagulation syndrome]. AB - Since disseminated intravascular coagulation (DIC) may directly reflect the abnormal regulation of the fibrinolytic system by endothelial cells, we have measured the levels of tissue-type plasminogen activator (t-PA), type 1 PA inhibitor (PAI-1) and t-PA . PAI-1 complex which is formed as a result of interaction on the two factors, in the plasma of patients with DIC (n = 51) and healthy controls (n = 42). Antigens of t-PA, PAI-1 and t-PA . PAI-1 complex were significantly increased in the DIC plasma (36.4 +/- 25.1, 106.8 +/- 54.7 and 46.6 +/- 34.5 ng/ml, respectively) compared with those in normal plasma (8.5 +/- 4.3, 54.4 +/- 21.2 and 8.6 +/- 3.5 ng/ml, respectively). The molar ratio of t-PA to PAI-1 was much higher in the DIC plasma (1:3) than in normal plasma (1:6), which caused enhancement of the whole fibrinolytic activity in the DIC plasma. These changes resulted in significant consumption of plasminogen, alpha 2-plasmin inhibitor (alpha 2-PI) and a significant increase of plasmin . alpha 2-PI complex (PPI) and D-dimer. These results suggest that t-PA and its specific inhibitor PAI 1 both of which are secreted from endothelial cells into blood, play an important role on the progress of DIC. PMID- 1920865 TI - [Clinical application of clinical laboratory tests]. AB - Recent advances in clinical laboratory tests have made it possible to study and clarify the pathogenesis of various diseases from various aspects. Such major advances can be very useful for the treatment and prophylaxis of diseases. Better tests can clarify the mutual relationships among diseases. Unfortunately, however, many clinical tests are not used effectively because they are not adequately understood. On this occasion, we are being given the opportunity to learn about the most recent clinical tests related to blood coagulation and fibrinolysis. These tests offer us the means of elucidating the pathogenesis of diseases. By applying the knowledge gained at this workshop in our clinical practice, we will be able to repay, in a small way, Dr. Matsuo, the chairman, for his efforts in the planning of this workshop. PMID- 1920866 TI - [Coagulation abnormalities in stroke--disseminated intravascular coagulation as a complication of subarachnoid hemorrhage]. AB - To determine the pathogenesis of the symptomatic vasospasm (SV) following subarachnoid hemorrhage (SAH), we compared the difference in coagulation activity between 52 aneurysmal patients with SV and 20 patients without SV. The hypercoagulable state was scored according to the Disseminated Intravascular Coagulation (DIC) scoring system. Our clinical studies showed that severe SAH following aneurysmal rupture caused the hypercoagulable state and there was a good correlation between the degree of the hypercoagulable state, the severity of SV and outcome of the aneurysmal patients. We stressed in this report that the monitoring of the blood coagulation and fibrinolytic activities is very important in severe SAH and that the hypercoagulable state after SAH plays an important role on the occurrence of SV. PMID- 1920867 TI - [Study on serum neopterin concentration in hemophiliacs with anti-human immunodeficiency-virus type I antibody]. AB - The present study was undertaken to discuss whether measurement of neopterin (NP) released into blood from monocytes/macrophage following activation of lymphocytes were useful tool to predict development of AIDS after HIV-1 infection. The subjects used for this study were eighty one cases of hemophilia, of whom 47 cases were HIV-1 antibody tested positive. Serum NP concentration (15.0 +/- 13.8 nmol/l) in anti-HIV-1 antibody-positive group was higher than in-negative group (5.7 +/- 3.3 nmol/l) (p less than 0.05), in which there was no case whose serum NP level amounted to more than 20 nmol/l. In anti-HIV-1 antibody-positive group, in which CD4/CD8 lymphocyte ratio was less than 0.4, serum NP level was significantly higher than in the group whose lymphocyte ratio was more than 0.5 (p less than 0.05). This result represents that there is a reverse correlation of NP concentration with the developing level of immunodeficiency. Furthermore, in eight cases who developed AIDS, serum NP levels turned to increase from several months or earlier until in all cases the levels were more than 30 nmol/l. In three cases of five who were dead, serum NP concentration had decreased to death since several months through one year. These findings reveal that measurement of serum NP concentration is correlated with clinical outcome after HIV-1 infection and it is useful as the marker for prediction of AIDS development. Also these findings represent that a parallel application of serum NP assay to CD4 lymphocyte counting, detection of anti-HIV-1 antibody, IgA, beta 2-microglobulin assays can predict the outcome of the HIV-1 infection more precisely. PMID- 1920869 TI - [Differentiation between fibrin degradation products and fibrinogen degradation products by using newly developed ELISAs]. AB - We should distinguish fibrin degradation products (FbDP) from fibrinogen degradation products (FgDP) in order to analyze fibrinolysis in vivo. We analyzed some disorders associated with hyperfibrinolytic states using ELISA for FbDP, FgDP and total fibrin (ogen) degradation products (TDP) (ORGANON TEKNIKA). Each ELISA was useful in terms of reproducibility and dilution linearity of plasma samples. There was no cross-reaction between FbDP and FgDP. The FgDP/FbDP ratio in normal individuals was 1.65. In patients with DIC, it was 0.43, with FgDP level being increased. These results suggest that fibrinolysis is enhanced in patients with DIC, but it is accompanied by fibrinogenolysis. On the other hand, the FgDP/FbDP ratio in patients given urokinase (UK) was 2.88. This suggests that fibrinogenolysis is enhanced in them. In our study, the FgDP/FbDP ratio increased as DIC improved. Thus, we can regard this as an index of therapeutic effects in patients with DIC. We conclude that these three ELISA are useful in analyzing disorders associated with hyperfibrinolytic states. PMID- 1920868 TI - [Examination of the inhibitor to factor VIII in non-haemophilic patient]. AB - We examined an inhibitor to factor VIII in non-haemophilic patient who had been developed widely spread ecchymosis and intramuscular bleeding. He had no previous personal or family history of abnormal bleeding tendency. His laboratory data was all normal except examination for blood coagulation. Coagulation studies showed prolonged activated partial thromboplastin time (48 sec) and decreased factor VIII activity (8%). The activity of the inhibitor to factor VIII was demonstrated to be 4.0 Bethesda unit. By the studies of dilution and time response curve, this inhibitor was found to inhibit up to 90% of factor VIII activity but not 100%. This inhibitor was shown to be IgG by protein-A affinity chromatography. In addition, bleeding time was prolonged in the patient. The value of von Willebrand factor antigen was 200%, but that of Ristocetin cofactor was 93%. Since the gel filtration analysis indicated that this inhibitor also suppressed Ristocetin cofactor activity, the relatively low value of Ristocetin cofactor might occur through the action of the inhibitor. These data suggest that patient's inhibitor react to factor VIII high molecular subunit. PMID- 1920870 TI - [Serum cholesterol levels in normal subjects taking into consideration the accuracy of the measuring system]. AB - Serum cholesterol levels were determined in 5,843 normal subjects aged zero to seventy years. The accuracy of our assay method was checked by Standard Reference Material 909 and Certified Reference Serum, both of which were supplied by the National Bureau of Standards. Reference values of serum cholesterol were confirmed for each age group. That of male subjects in the 15-20 year age group was within a range of 109-203 mg/dl, and that of female subjects in the 20-25 year age group was within a range of 133-215 mg/dl. Therefore, among normal subjects, the above-mentioned age groups had the lowest serum cholesterol levels. Serum cholesterol levels increased with age in both male and female subjects. The upper limit of cholesterol levels was 248 mg/dl for males in the 50-60 year age group and 284 mg/dl for females in the same age group. We observed the necessity of paying consideration those changes which occur with aging, in the determination of reference values of serum cholesterol. Our findings also showed that serum cholesterol levels remained nearly constant in male subjects of all age groups over a period of 25 years. However, we found mean levels in female subjects in the 50-70 year age groups to be significantly elevated, when compared with those observed in persons in the same age group of 25 years previous. We also found that the mean cholesterol level in girls aged 12 years was higher than that of boys the same age. PMID- 1920872 TI - [Cardiac function abnormalities and biochemical changes in myocardial ischemia]. AB - The relationship between myocardial ischemia and biochemical changes has been well documented. For example, hyperlipidemia is one of the largest risk factors for the development of coronary artery disease. Decreased coronary blood flow produces various changes in cardiac metabolism, which cause severe cardiac function abnormalities, including heart failure and arrhythmias. Many biochemical markers have been used for both diagnosis and evaluation of the severity of myocardial infarction. In this symposium the speakers have discussed: 1) the relationship between the changes in the ionic environments in the intra- and extra-cellular spaces and the genesis of cardiac arrhythmias, with special reference to the role of increased intracellular resistance in conduction delay during ischemia (Dr. Takao Fujino), 2) metabolic basis of ECG abnormalities in ischemic heart disease and the role of intra-coronary ECG recordings in the evaluation of cardiac ischemia (Dr. Tetsunori Saikawa), and 3) biochemical changes associated with exercise and other stresses, with special reference to the roles of increased catecholamines and decreased blood fluidity in the genesis of cardiac abnormalities (Dr. Takehiko Fujino). Prof. Takeshi Kanno gave a special lecture entitled "Approaches from clinical laboratory to hereditary variants". He showed an excellent model of approach from clinical laboratory medicine to detect important biochemical abnormalities which may be overlooked by routine daily analyses in the clinical laboratory. PMID- 1920871 TI - [Studies on plasma immunoreactive human brain natriuretic peptide (hBNP) levels in patients with congestive heart failure and present forms of hBNP in human cardiac ventricle]. AB - By using a specific radioimmunoassay (RIA) for human brain natriuretic peptide (hBNP), we measured immunoreactive hBNP (ir-hBNP) in plasma from patients with congestive heart failure (CHF). There appeared to be relationship between the enhanced ir-hBNP secretory activity and the severity of the failing heart as well as that of immunoreactive human atrial natriuretic peptide (ir-hANP). However, the secretion of ir-hBNP was augmented much more than that of ir-hANP in sever CHF patients. Gel permeation chromatography coupled with the RIA revealed that ir hBNP in human ventricle is composed with gamma-hBNP and hBNP (1-32) as well as that of human atrium. However, we found differences of the gamma-hBNP/hBNP (1-32) ratio in atrial and ventricular tissues. These findings suggest that the hBNP secretion mechanism differ in the two areas of human heart. PMID- 1920873 TI - [Arrhythmogenesis of changes in cellular ionic environments: ischemia-induced increase in intracellular resistance and slow conduction]. AB - Cardiac action potentials result from the influx of sodium and calcium ions and the efflux of potassium ions. In the ischemic myocardium, homeostasis of ionic environments are seriously disturbed, producing abnormalities in impulse generation and propagation. Conduction velocity of impulse is directly related to the maximum upstroke velocity of the action potential (Vmax) and inversely related to the intracellular resistance (r1). During ischemic events, Vmax decreases and r1 increases. These changes in Vmax and r1 greatly diminish the conduction velocity and can lead to the occurrence of various arrhythmias. To evaluate the role of the increase in r1 on conduction slowing in cardiac ischemia, we simultaneously measured the changes in Vmax, r1 and conduction velocity of the papillary muscle of guinea pig superfused with simulated ischemia (SI) solution (K+: 13 mM, pH: 6.0, pO2: 20-30 mmHg, glucose: 0 mM). After SI, both Vmax and conduction velocity decreased and r1 increased. When Vmax alone was taken into consideration, the measured conduction was slower than that predicted from the continuous cable theory. However, by compensating the value of Vmax by the change in r1, we could explain the change in measured conduction velocity by the cable theory. We conclude that, in myocardial ischemia, increase of r1 as well as diminished Vmax causes the conduction slowing and hence can lead to clinical arrhythmia such as reentrant tachycardia. PMID- 1920874 TI - [Serial changes in QT interval during the course of acute ischemic episode: with special reference to intracoronary electrograms]. AB - The change in electrocardiogram (ECG) during percutaneous transluminal coronary angioplasty (PTCA) was investigated by recording both standard 12 lead ECG (surface ECG) and intracoronary electrogram (ic-ECG) before, during and after PTCA with right atrium pacing (80/min). During the ischemia induced by PTCA, the amplitude of QRS complex revealed an initial decrease in amplitude and later increase in ic-ECG, however, it only showed an initial decrease in surface ECG up to 5 minutes, while the QRS interval showed a significant decrease in only in ic ECG (77 +/- 14 vs 75 +/- 13 msec). The QT interval became shorter with the increase in the duration of ischemia, the difference being statistically significant even for the initial 20 seconds of ischemia in both ic-ECG (398 +/- 27 vs 370 +/- 22) and surface ECG. In the case of acute myocardial infarction, the direction of T wave and QT interval seemed to depend on the degree of reperfusion. Hence, in patients who underwent successful reperfusion therapy the QT interval was lengthened initially and later shortened, cardiac function preserved and T wave normalized in anteroseptal myocardial infarction, while in those who had unsuccessful reperfusion the QT interval was progressively lengthened, cardiac function was not preserved well and T wave was not normalized. Therefore, in patients with a positive T wave the QT interval was shorter (382.4 +/- 42.6 vs 448.7 +/- 29.7 msec), with better fractional shortening (4.24 +/- 2.2 vs 1.95 +/- 1.2) and better left ventricular ejection fraction (68.1 +/- 6.1 vs 52.9 +/- 14.7%) than in the patients with negative T wave in lead V2 in the chronic stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920875 TI - [Screening of symptom poor hereditary disorders in clinical laboratories]. AB - Detection of symptom poor hereditary disorders from laboratory data is one of the targets of the laboratory data analysis system. Symptom poor hereditary disorders include; 1) pharmacogenetic disorders, 2) heterozygous individuals of hereditary disorders, 3) early or symptomless stage of hereditary disorders and 4) primary symptom poor hereditary disorders. The following cases of pseudocholinesterase silent gene variants, lactate dehydrogenase M and H subunit deficiencies, heterozygous individuals of aphosphatasia and Xanthinuria were screened from the laboratory data analysis system for hereditary disorders. The characteristics of the laboratory data, and clinical features of these symptom poor hereditary disorders were described and discussed. PMID- 1920876 TI - [Long-term observation of individual erythrocyte sedimentation rate and its relation to other tests variation]. AB - We have studied individual changes of erythrocyte sedimentation rate (ESR) in 30 so-called healthy subjects by examining them 2-4 times a year for 14-20 years. The results showed big differences in the same subjects during these period, and clearly different values were obtained between male and female groups. Furthermore, increased values were seen in accordance with aging in all except 3 cases. Even this aging effect showed remarkable individual differences, which, however, lead to a better correlation to aging than increase of gamma-globulin. In many cases with ESR values out of +/- 2 SD of their mean values, their other laboratory findings such as general peripheral blood tests and plasma protein tests etc., showed also the results out of +/- 2 SD of their mean values. These results show that ESR can be a useful tool as one of screening parameters. PMID- 1920877 TI - [Humoral immunity and lymphocyte subsets in patients with dilated cardiomyopathy]. AB - We examined immunological abnormalities in patients with dilated cardiomyopathy (DCM) and reviewed their medical histories, NYHA classifications, electrocardiogram findings and chest X-Ray findings with regard to severity of DCM. Elevated CD4/CD8 ratio as well as decreased number of CD8 cells in lymphocyte subsets was recognized. These abnormalities were particularly noted in patients with past history of myocarditis. NYHA IV class increases in CTR and left ventricular dimension, and a reduced ejection fraction. These findings suggest that lasting of myocardial damage causes immunological abnormalities and the examination of DCM patients' immunological status is useful in anticipating disease process and determining medical treatment. PMID- 1920878 TI - [Enzyme immunoassay of urinary apolipoprotein H and its application for detecting incipient diabetic nephropathy]. AB - In order to elucidate the clinical significance of urinary apolipoprotein H (Apo H), otherwise known as beta 2-glycoprotein I, we first developed a non competitive enzyme immunoassay (EIA) to quantify urinary Apo H levels. The measurable range of this assay was about 2 ng/ml to 100 ng/ml. The intra- and inter-assay coefficients of variation were 2.0 to 4.7% and 8.3 to 17.0%, respectively. These results indicated that this assay had high sensitivity and good reproducibility, and that it was useful for clinical study. We then determined urinary Apo H levels in 24 normal subjects and 36 diabetics using this assay. The mean urinary Apo H index (urinary Apo H/cr ratio), in 20 patients without proteinuria, who were regarded as patients without nephropathy, was 569 +/- 560 (X10(-3) mg/g.cr) and significantly higher than in normal subjects (252 +/- 147, p less than 0.01). The mean urinary Apo H index in 16 patients with overt proteinuria was 1,507 +/- 3,701 and also higher than in normal subjects (p less than 0.01). These results taken collectively indicate that urinary Apo H level using the EIA may be a new sensitive marker for detecting minor change of glomerular basement membrane in diabetics. PMID- 1920879 TI - [Application of the polymerase chain reaction (PCR) in the diagnosis of Hb S beta(+)-thalassemia]. AB - Isoelectric focusing of the hemolysate prepared from a two-year-old American black boy with microcytic hypochromia showed the presence of a high percentage (63.3%) of such Hb variant as Hb S, while the levels of Hb A, Hb F and Hb A2 were 20.0%, 12.7%, and 4.0%, respectively. The ratio of the non-alpha-chain to the alpha-chain of the biosynthesized globin chains was 0.49. The variant was identified as Hb S by amino acid analysis of the abnormal peptide (beta T-1) and digestion of DNA amplified by the polymerase chain reaction with enzyme Eco 81 I. This was further confirmed by DNA sequencing. DNA sequencing of a beta-gene without the beta s-mutation revealed a nucleotide change of T to C in the polyadenylation signal sequence AATAAA 3' to the beta-gene, resulting in beta(+) thalassemia. These results are consistent with the existence of a beta s-gene and a beta(+)-thalassemia gene in trans. PMID- 1920880 TI - [The characteristic of the distribution of C apolipoproteins in umbilical cord blood]. AB - The profiles of C-II apolipoprotein (apo C-II) or apo C-III were determined in ten normal full-term female neonates and ten healthy adult females, to characterize the distribution of apo C in umbilical cord blood (UCB). The profiles of the distribution of apo C were electrophoretically obtained. After agarose gel-immunofixation electrophoresis using anti-apo C-II or anti-apo C-III antisera, the immune complexes of apo C-II or apo C-III selectively remained in the gels by salting out the non-immunoreacted proteins and were stained to be measured by the densitometry. So, apo C in high density lipoprotein (HDL) were satisfactorily separated from apo C in apo B-containing lipoproteins (LPcB). The apolipoproteins levels in mg/dl +/- SD for all UCB were; apo A-I = 84.4 +/- 11.8; apo A-II = 17.8 +/- 5.9; apo B = 14.0 +/- 4.2; apo C-II = 2.4 +/- 0.4; apo C-III = 3.6 +/- 0.9; apo E = 3.7 +/- 1.2, and these values were, respectively, 62.5%, 55.3%, 15.9%, 68.6%, 48.0% and 90.2% of the values obtained in adult blood. Apo C profiles in UCB were characterized by the distributions of the majority of apo C to HDL, in the same manner as the distribution of apo E, and were similar to the apo C profiles acquired from adult patients with hypo-beta lipoproteinemias. The percentages of apo C-II and apo C-III in umbilical HDL to total apo C-II and total apo C-III were high, 90.3% and 91.8%, compared to the adult HDL levels of 52.4% and 51.5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920881 TI - [Problems of Mason-Likar lead system in treadmill exercise electrocardiography]. AB - A Mason-Likar (M-L) leads system has been widely used in the exercise electrocardiography (ECG) using treadmill for the detection of myocardial ischemia. In routine treadmill exercise ECG using M-L lead, we often observe different patterns of ST-T forms those of II, III and aVF on bipolar leads. In this study, on 213 patients, conventional 12 lead ECG and the M-L lead placement ECG were recorded both at supine and standing positions. A careful analysis was made on all the records of patterns, durations, and amplitudes of QRS and T waves. We also evaluated the ST trendgram of patients with no ischemic changes proven exercise TI-201 myocardial single photon emission tomography (SPECT). Quantitative examination showed no significant differences between those in precordial leads of the standard and the M-L lead system in any subjects. The augmented amplitude of QRS and T waves, the disappearance of abnormal Q-waves in II, III, aVF lead, the negative inversion in QRS phase in lead aVL an left axis deviation were often recognized with M-L lead placement. In treadmill exercise ECG, ST depression more than 1 mm in II, III, aVF lead was noted 14 out of 17 patients with no ischemic changes. The all ST-T changes showed "not-decrescendo" type in ST trendgram. We concluded that rigorous evaluation for electrical axis, the configuration of ST-T waves and the existence of myocardial ischemia in leads II, III, aVF was necessary on treadmill exercise ECG using M-L lead replacement. PMID- 1920883 TI - [Auditory event-related potentials (ERPs) in healthy subjects and patients with dementia]. AB - To study the effects of aging and gender differences of ERP components, auditory ERPs were recorded in 106 healthy subjects. Forty-three patients with dementia of the Alzheimer type and 24 patients with vascular dementia were also studied. In healthy subjects, there was a significant positive linear correlation between P300 latency and age, with P300 latency increasing at the rate of 1.5 msec/year. Neither N100 nor P200 component was correlated with age. The amplitudes of N100, P200 and P300 components in females were slightly larger than those in males, but the differences were not significant. Not only P300 latencies but also P200 latencies were significantly different in healthy subjects, patients with dementia of the Alzheimer type and those with vascular dementia. In 74.4% of patients with dementia of the Alzheimer type and 62.5% of those with vascular dementia, the P300 latency was over 2 SE above the age-estimated regression line. The difference of the P300 latency prolongation may have resulted from the severity of dementia but not from the etiology of dementia. PMID- 1920882 TI - [EEG data filing system with personal computer and magneto-optical disc]. AB - We established a new computerized EEG filing system, in which an EEG machine was connected to an EEG filing unit which consisted of a personal computer with a 32 bit CPU, 18 channel analog -to-digital and digital-to-analog converters, and a magneto-optical disc driver. This system has the following merits. The system was space-saving, the space required to store the EEG data, being only 1/500 of that required for storing EEG record. Though the system had two independent EEG filing units, our original file configuration enabled us to have access to all of the recorded EEG data anytime for more than 10 years. The system enabled us to display EEG data continuously on the high resolution CRT, just as if turning the page of an EEG record paper, and through the quick scanning, enabled us to view the entire EEG pattern. Furthermore, the system enabled us to conduct reliable digital analysis for EEG data by entering the EEG data without artifacts into a data processor after confirmation on the display. In the system, we used data files with the MS-DOS operating system. This enabled us to analyze the data obtained by a personal computer operating on other systems, by transferring the data to a floppy disc operating on our system. Our EEG filing system allows quick access to data as well as mass data storage. PMID- 1920884 TI - [Auditory brain stem response in patients with consciousness disturbance]. AB - To investigate the prognosis for patients with consciousness disturbance, we recorded auditory brain stem response (ABR) in 35 patients with primary or secondary brain damage. For patients with secondary brain damage, the first ABR recorded after admission could be used not only to differentiate consciousness level but also to predict prognosis. However, for the patients with primary brain damage, the first ABR could not be used for either differentiating consciousness level or predicting prognosis. In addition, in two patients with secondary brain damage, the series of ABR recordings indicated that brain stem damage was reversible. PMID- 1920885 TI - [Anti-Borrelia burgdorferi antibody in dogs: Lyme disease as zoonosis]. AB - To obtain epidemiological data on human Lyme disease (LD) in Japan, anti Borrelia burgdorferi (Borrelia) antibody was measured in dogs by enzyme-linked immunosorbent assay (ELISA). The anti-Borrelia antibody titer was high in 106 (27.3%) of 387 clinically healthy dogs that may have a chance of tick bite but not in any of 31 negative control dogs not exposed to ticks; the difference of the antibody titer between two groups was significant. However, no signs of arthritis were observed in any of the 106 dogs with a high anti-Borrelia antibody titer. The antibody titer was also significantly differed between the age groups less than 1 year old and 1 year old or more, the group maintained indoors and that maintained outdoors, the group with tick bites and that without tick bites, and hounds and the other dogs but not between males and females or the group vaccinated and that unvaccinated with leptospires. According to districts, high antibody titers were observed in 20% of the dogs or more in Hokkaido, Saitama, Kanagawa, Niigata, Kyoto, Kochi, and Fukuoka Prefectures. These districts were nearly consistent with the distribution of the ticks. Western blot analysis of serum samples with a high anti-Borrelia antibody titer showed 31-, 41-, 66-, and 83-Kd bands, which are also observed in sera of human patients with LD. Though no dog had clinical signs of LD, dogs serologically positive for Borrelia were detected throughout the country. The data suggested that there were the dogs infected by Borrelia burgdorferi in Japan. The data on anti-Borrelia antibody in dogs obtained by ELISA may be very useful for studying the epidemiology of LD in humans. PMID- 1920886 TI - [Preparation and application of control sera for neuromuscular disorders]. AB - The lack of assayed quality control sera to reliably determine the presence of low creatinine, high creatinine, and high aldolase activity levels in patients with progressive muscular dystrophy prompted us to attempt the development of such sera. The mean serum creatinine and creatine values in patients with neuromuscular disorders were 0.24 mg/dl and 1.42 mg/dl, respectively. Aldolase activity spanned a wide range from normal to 273 IU/l. On the basis of these findings, sera containing 0.2 mg/dl of creatinine, 1.6 mg/dl of creatine, and 60 IU/l of aldolase activity were prepared by the reconstitution of pooled sera. The coefficients of variation (CVs) of creatinine assays for control sera containing 1.0 mg/dl or more were less than 1.5%. However, precision was poor at creatinine concentrations below 0.4 mg/dl, with CVs as high as 3.3%. Since the precision of creatinine measurement is poor at low concentrations, the creatinine assay has its own limitations if employed clinically for the purpose of evaluating renal function in patients with muscle atrophy or in children who have low serum creatinine levels. The high creatine and aldolase activity levels of the prepared control sera gave satisfactory results when analyzed for intra-assay and inter assay variation. PMID- 1920887 TI - [Histological study of heterotopic pancreas tissue of the stomach--histogenesis and immunohistochemical findings]. AB - Forty resected cases of heterotopic pancreas (15 of Heinrich's type I and 25 of type II) in the stomach were investigated. Acinic cells were more remarkably positive by pancreatic polypeptide and amylase in the cases of type I consisting of acinic cells, ducts and islet cells compared with those in type II consisting of acinic cells and ducts. Staining behavior by insulin, gastrin, glucagon, somatostatin and serotonin was similar to that of normal pancreas. However, the intestinal epithelium containing goblet cells and pyloric gland-like glands consisting of the cells with clear cytoplasm were not infrequently produced from the ducts in the lesions of type II. Muscle fibers with transition to muscularis mucosae were more frequently intermingled in the lesions of type II compared with type I. Acinic cell-differentiation in the mucosa apart from the main lesion was found in several cases of type II. It was suspected that there are two types of histogenesis for the heterotopic pancreas in the stomach; one arises from the fetal immigration of pancreas tissue in the stomach and the other from the immature gastric mucosal penetration into the submucosa with secondary differentiation to the pancreas tissue. PMID- 1920888 TI - [Adult T-cell leukemia lymphoma with metastatic calcification]. AB - A 52-year-old man, who came from Kagoshima prefecture, was hospitalized because of lumbago and lymphadenopathy. On admission, mild anemia and leukocytosis with atypical lymphoid cells were seen in the peripheral blood. Flow cytometry of the abnormal lymphocytes showed that they expressed CD4, and CD25, but not CD8. Anti HTLV I antibody was expressed in the serum. Atypical lymphoid cells had proviral DNA with restriction enzyme EcoRI. Lymphnode biopsy was performed and the specimens of lymphnode showed diffuse infiltration of abnormal lymphocytes. So we diagnosed Adult T-cell leukemia lymphoma. The patient's serum calcium level was increased, so he lost consciousness and became oliguric and developed acute renal failure. Hemodialysis was required to control azotemia. During the time of hemodialysis, cardiac arrest was occurred and he died. Autopsy confirmed the presence of a metastatic calcification in various organs, such as myocardium, alveolar septa of the lungs, and gastric mucosa. A metastatic calcinosis was found in the myocardium, which was thought to be the cause of his heart failure. But at the ATLL cells didn't infiltrate in the myocardium. Calcinosis was a significant complication of neoplastic disease in these patients and contributed to morbidity and mortality. PMID- 1920889 TI - [Serodiagnosis of Lyme disease by ELISA using Borrelia burgdorferi flagellum antigen]. AB - Antibodies to a 41,000 (41 kD) polypeptide in flagella of Borrelia burgdorferi were measured in patients with Lyme disease in Japan by flagellum ELISA. The IgG and IgM Classes of antibodies to a flagellum antigens were detected in the sera as early as 0.5 months after infection. The IgG antibodies continued to exist in their sera for more than one year, while the IgM antibodies quickly faded out from their sera. With respect to a diagnostic specificity of the flagellum ELISA, false positive reactions showing more than 10% were observed in sera with high levels of IgG or IgM, and with anti-syphilis antibody. This method, however, was unaffected by sera with high levels of IgA, rheumatoid factor or anti-nuclear antibody. In three cases of patients with erythema migrans preceded by tick-bite, and treated with antibiotics, seronegative results were observed by a immunoperoxidase (IP) test. Since two of them showed the positive level of IgM antibody by the flagellum ELISA, this method seems to be more sensitive and useful than the IP test for serodiagnosis of the Lyme disease. PMID- 1920891 TI - [Inhibitory effect of arbutin on melanogenesis--biochemical study using cultured B16 melanoma cells]. AB - Inhibitory effect of arbutin (hydroquinone-beta-D-glucopyranoside) on the melanogenesis was studied biochemically using cultured B16 melanoma cells. The maximum arbutin concentration lacking an inhibitory effect on cell growth was 5 X 10(-5) M. At this concentration, melanin content per cell was decreased significantly to about 39%, compared with that of arbutin untreated cells. Also, tyrosinase activity of arbutin treated cells was decreased significantly. When arbutin was added to B16 melanoma cell suspension, arbutin was not hydrolyzed to liberate hydroquinone. Further, tyrosinase activity in crude preparations from B16 melanoma cells was inhibited by arbutin. From these results, it is suggested that arbutin can inhibit the melanogenesis by affecting not only the synthesis but also the activity of tyrosinase rather than by killing melanocytes B16 melanoma cells. Also, it is suggested that hydroquinone is not responsible for the inhibitory effect of arbutin on the melanogenesis. PMID- 1920890 TI - [Differentiation of intestinal candidial colonization from invasive candidiasis by measuring serum level of D-arabinitol in combination with oral administration of low dose amphotericin B]. AB - The measurement of D-arabinitol in serum has been reported to be useful for the diagnosis of invasive candidiasis. However, excessive proliferation of Candida species in intestinal tract often leads false positive result of serum D arabinitol. Based on the evidence that amphotericin B (AMPH) is scarcely absorbed from intestinal tract and inhibits the proliferation of Candida species only in intestinal tract, we have developed a simple differentiation method of intestinal candida colonization from invasive candidiasis by measuring serum level of D arabinitol in combination with oral administration of low dose AMPH. AMPH, 600 mg/day for 2 days was orally administered to five patients with hematological malignancies who showed more than 1.7 mumol/mg of D-arabinitol/creatinine ratio (D/C ratio) in serum without any evidence of invasive candidiasis. D/C ratios were markedly decreased and normalized after the oral administration of low dose AMPH. While, in a patient with invasive candidiasis in whom Candida species was detected by blood cultures, D/C ratio remained unchanged in spite of oral administration of AMPH. These observations suggest that this method is a simple and reliable diagnostic method to distinguish intestinal candida colonization from true invasive candidiasis. PMID- 1920892 TI - [Evaluation of the past history of chilblain in cases of systemic lupus erythematosus (SLE) and its similar diseases]. AB - We sent out a questionnaire to 47 patients of SLE and its similar diseases as to their past histories of chilblain. The results of the patients were compared to those of 141 cases of control. Although the percentage of cases who had revealed chilblain frequently (40.0%) and the age of chilblain onset (mean: 10.8 years old) in SLE group were not significantly different from those of control (28.4% and 12.4 years old, respectively), the chilblain which SLE patients developed had some characteristics compared to that of control, (1) higher incidence of chilblain episodes, (2) longer duration until cure, (3) more liability that chilblain leads to erosion or ulceration and (4) frequent occurrence of chilblain in the other seasons than winter. Especially SLE patients with the characteristic of (4) had higher association rates of Raynaud's phenomena, chilblain LE and livedo, suggesting disorder of peripheral circulation. It was also revealed that females are generally more liable to develop chilblain than males (females: 40.0%, males: 13.1%). Those results suggest some important relationship between chilblain and LE lesions. It is supposed that chilblain with the characteristics described above may possibly be transformed into LE lesions. PMID- 1920893 TI - [Clofibrate treatment of psoriasis with hypertriglycemia--clinical, histological and laboratory analysis]. AB - Abnormalities of triglyceride (TG) metabolism are considered to play an important role in pathogenesis of psoriasis. Two psoriatic patients with hypertriglycemia were treated with 750 mg of oral Clofibrate daily. While they were treated, both patients showed improvement of psoriasis. Upon cessation of treatment the lesions returned. During the treatment, levels of serum TG, apolipoprotein C-III (apo C III), and apo E were reduced significantly. The analysis of serum fatty acids revealed a change in the level of linoleic acid. The serum linoleic acid level, which had been low in both cases before the treatment, increased in one case and decreased in other during the treatment. In the biopsy specimen from the post treatment plaque, both capillary proliferation and endothelial swelling in the dermis were less prominent. There was a moderate reduction in the number of lymphocytic cells, and an increase in that of histiocytic cells. Clofibrate treatment improved TG metabolism and the histological and clinical findings in the psoriatic lesion. PMID- 1920895 TI - [A case report of progressive symmetric erythrokeratodermia and a review of progressive erythrokeratodermia in Japan]. AB - The patient is a 5-year-old boy. There was no family history of the similar skin eruptions. The erythema with scales appeared on his head, face and neck at 1 month of birth. The erythematous hyperkeratotic plaques spread symmetrically. There was no follicular components. The eruption was chronic and persistent. In histopathology, hyperkeratosis with focal parakeratosis, acanthosis and intact granular layer were observed. In electron microscopy, a large number of mitochondria that frequently appeared to be swollen and lipidlike vacuoles in corneocytes were observed. On account of the features, we diagnosed this case as progressive symmetric erythrokeratodermia (PSE). PSE is a rare disease, and besides, it is difficult to define PSE because of contradictions in existing literatures, the variability of clinical expression and the lack of histologic, hereditary, and biochemical criteria. Nearly 70 cases were diagnosed as PSE and its variants in Japan i.e. 4 cases with PSE, 8 cases with progressive erythrokeratodermia, and 58 cases with Asahi-Ijiri disease and its variants. However, only 2 cases diagnosed as PSE and 4 cases nominated as others satisfied the recently established criteria by Ruiz-Maldonado, et al. In this paper, reported cases of PSE and its variants were reviewed and reassessed. PMID- 1920894 TI - [A case of Farber's disease--histochemical, electron microscopic and biochemical studies]. AB - A case of Farber's disease (disseminated lipogranulomatosis) is reported. A Japanese boy presented with progressive joint deformity, a hoarse voice, mental retardation and skin granulomatous lesions. He died of bronchopneumonia at the age of 2 years. Biopsied specimen from the perianal granulomatous lesion showed many macrophage contained lipids, and acidic oligo-, or polysaccharides, or, glycoconjugates. Electron microscopic study revealed, in addition to curvilinear tubular bodies (Farber's bodies), numerous granular structures accumulated in the cytoplasm of the macrophage. Biochemical analysis demonstrated a storage of free ceramide in the patient's liver, and confirmed the patient's diagnosis. This is the 5th case reported in Japan. PMID- 1920896 TI - [Endoscopic ultrasonography in the assessment of invasive cardiac cancer]. AB - The aim of this study was to assess the accuracy and limitation of Endoscopic ultrasonography (EUS) in the preoperative evaluation of the cardiac cancer (cancer in the area less than 2 cm from the esophago-gastric junction). EUS was preoperatively performed in 20 patients with cardiac cancer. These cases were visualized by the water immersion method and balloon contact method. The results were correlated with the histology of resected specimens. EUS was accurate in assessing the depth of tumor infiltration. Over all accuracy of EUS for cardiac cancer was 90%. Recognition of ultrasonographic patterns had enabled us to judge the mode of tumor infiltration whether expansive or infiltrative. Microscopical spread over 5 mm to the esophagus of the cardiac cancer could be detected by EUS. EUS was accurate in diagnosing thoracic lymph nodes (No. 110, 111, 112) metastasis of the cardiac cancer (accuracy 86%). EUS was valuable in the clinical diagnosis of the cardiac cancer. PMID- 1920897 TI - [Mucosubstance and lectin histochemistry of DMH induced colonic tumor in rats]. AB - Histo-pathological appearances of DMH-induced colonic tumor in Wistar rats were sequentially observed upto the 35th week after the drug administration. In our series, 28 tumors were successfully induced in the colonic mucosa of 19 out of 64 rats treated with DMH, and they were histologically diagnosed as adenocarcinoma. However, there were differences in the histo-pathological findings of the carcinoma between the distal colon and the proximal colon in rats. That is, the slowly growing type of well differentiated adenocarcinoma was likely to originate from the proper mucosa in the distal colon, while in the proximal colon the rapidly growing type of tumor did from atypical glands in the lymphoid follicles. Therefore, it was suggested that histogenesis and growing processes of the carcinoma were differed in the distal colon from that in the proximal colon in rats. Second, epithelial mucosubstances and lectin-binding properties of these lesions were examined histochemically. There were differences in the lectin binding patterns of UEA-I and PNA between carcinomas and/or atypical glands in the lymphoid follicle and normal background mucosa in rat colon. In the UEA-I staining, almost all tumors were positively stained except for one case, and in the well differentiated type a positive staining was discernible at the cell apex and secretory product in tumors, while in the undifferentiated type, it was seen at the cytoplasma and secretory product. From these histopathological and histochemical studies it may be concluded that these lectins is likely to be useful as tumor markers for the large bowel, and also effective for a diagnosis of minute carcinoma in the large bowel. PMID- 1920898 TI - [Plasminogen activator activity and its separative measurement in the gastric mucosa of liver cirrhotics]. AB - Plasminogen activator (PA) activity of the gastric mucosa of liver cirrhotics was measured by use of Glt-Gly-Arg-MCA as the substrate. Gastroduodenal mucosal lesions were more frequently seen in cirrhotic patients with red spot of the gastric mucosa (RS (+) group) as compared to the cases without red spot (RS (-) group). RS (+) group had poor liver function as compared to RS (-) group. PA activity of the gastric mucosa in RS (+) group was higher than RS (-) and control groups. Furthermore, the elevated PA activity was highly associated with severe liver damage estimated by routine liver function test and Child's classification. Separately quantitative assay of PAs was performed by using Lysine-Sepharose 4B chromatography. Both the tissue type and urokinase type PA were higher in the RS (+) group than in control group. These results suggest that accelerated tissue fibrinolytic activity is one of the causative factors of gastric mucosal bleeding in cirrhotic patients with red spot. PMID- 1920899 TI - [Pathogenesis of black gallstones associated with hemolytic disease]. AB - In order to investigate the pathogenesis of black gallstones associated with hemolytic disorders, experimental and clinical studies were performed. Firstly, a one-shot injection of bilirubin and hemolyzed blood, and a continuous injection of bilirubin were performed in mongrel dogs with the aim to analyze the changes of hepatic and gallbladder bile composition. Secondly, gallbladder bile obtained intraoperatively from the patients with black gallstones associated with hemolytic disease, patients with black stones not associated with hemolytic disease and patients with gallbladder polyp were analyzed in order to compare the characteristics of hemolytic patients' bile with those of the model animals. High concentration of total bilirubin and increased proportion of bilirubin monoconjugate (BMC) fraction was observed in the bile of patients with black stone associated with hemolytic disease compared with the bile of the patients of other two groups. Bile pH, total calcium concentration and ionized calcium concentration were similar in all the groups. Total bile lipid concentration of hemolytic patients was decreased but the ratio of total bile acid to total lipid was increased. Both bolus injection of bilirubin and hemolyzed blood produced an increase of total bilirubin concentration and BMC in hepatic bile. Continuous bilirubin injection for 7 days induced an increase of total bilirubin and BMC in both hepatic and gallbladder bile. These results suggest that the conjugating capacity of the hepatocyte is surpassed by the excessive amount of bilirubin produced after hemolysis, producing therefore, an increased BMC and unconjugated bilirubin content in bile. This increased content can precipitate in bile as black gallstones. PMID- 1920900 TI - [The inhibitory effect of cholecystokinin on phosphatidylcholine synthesis in isolated rat pancreatic acini]. AB - The effects of cholecystokinin (CCK) and other pancreatic secretagogues on phosphatidylcholine (PC) synthesis were studied in isolated rat pancreatic acini. When acini were incubated with [3H] choline in the presence of 1 nM CCK octapeptide (CCK8) for 60 min, the incorporations of [3H] choline to both water soluble choline metabolites and PC in acini were reduced by CCK8 to 74% and 41% of control, respectively. Pulse-chase study revealed that CCK reduced both the disappearance of phosphocholine and the synthesis of PC. Ca(2+)-mobilizing secretagogues such as carbamylcholine and Ca2+ ionophore A23187 also reduced PC synthesis to the same extent as CCK8. By contrast, neither cAMP-dependent secretagogues such as secretin and dibutyryl cAMP nor a phorbol ester had any effect on PC synthesis in acini. These results suggest that CCK inhibits PC synthesis by inducing both the reduction of choline uptake into acini and the inhibition of CTP: phosphocholine cytidylyltransferase activity. This hormonal regulation of PC synthesis via CDP-choline pathway appears to be mediated by Ca(2+)-dependent pathway but not by cAMP- or protein kinase C-dependent pathway. PMID- 1920901 TI - [A case report of esophageal intramural pseudodiverticulosis associated with esophageal web]. PMID- 1920902 TI - [A case of esophageal intramural pseudodiverticulosis]. PMID- 1920903 TI - [A successfully treated case of fundic varices by retrograde transvenous obliteration with balloon]. PMID- 1920904 TI - [A case of Menetrier's disease complicated during the clinical course of bronchial asthma]. PMID- 1920905 TI - [A case of "non specific multiple ulcers of the small intestine" with perforation as a presenting sign]. PMID- 1920906 TI - [Two patients of CREST-primary biliary cirrhosis overlap syndrome with common HLA types]. PMID- 1920907 TI - [A case of intrahepatic portal vein aneurysm with arterioportal fistula and severe portal hypertension]. PMID- 1920908 TI - [A case of congenital malformation of the biliary duct with strange dilatation and interlobar connection of the intrahepatic biliary duct]. PMID- 1920909 TI - [A case of acute hepatitis type A showing simultaneous occurrence of pure red cell aplasia and hemolytic anemia]. PMID- 1920910 TI - [A case of portosystemic encephalopathy--percutaneous transhepatic embolization of shunt]. PMID- 1920911 TI - [Intrahepatic cholelithiasis associated with accessory hepato-biliary duct--a case report with special reference to possible role of accessory hepato-biliary duct in stone formation]. PMID- 1920912 TI - A Japanese family pedigree of patients with severe combined immunodeficiency disease with X-linked inheritance. AB - We described three patients with severe combined immunodeficiency disease (SCID) with B lymphocytes from a single family. Adenosine deaminase and purine nucleoside phosphorylase activities were normal. Two of them received bone marrow transplantation from an HLA haplotype-mismatched mother and an HLA-identical sibling, respectively, with successful immunological reconstitution. Another patient died of severe pneumonia. X-linked inheritance was suggested through the analysis of the pedigree extending four generations. This is probably the largest SCID kindred reported in Japan. PMID- 1920913 TI - De novo interstitial deletion of 4q[46,XX,del(4)(q27q28.2)] with intact blood group-MN locus, confining its locus to 4q28.2-4q31.1. AB - We report a malformed female infant with de novo interstitial deletion of 4q[46,XX,del(4)(q27q28.2)]. The MN blood type analysis of the family members showed that the patient had an intact blood group-MN locus. The locus of the gene responsible for the MN antigen activity is confined to a 4q28.2-4q31.1 segment on the basis of the result of this patient and the previous mapping data. PMID- 1920914 TI - Refined determination of breakpoints of the translocation t(1;7) associated with signs of HMC syndrome. AB - High-resolution band analysis was performed in order to precisely determine the breakpoints of a de novo chromosome translocation, t(1;7), which is associated with clinical signs of HMC syndrome (McKusick's #239800). The breakpoints were found to be at 1q31.2 and 7p15.1-p15.3, respectively. The finding of the translocation in this case might not be coincidental, but rather suggestive of the gene locus responsible for the development of HMC syndrome at either site of the breakpoints. PMID- 1920915 TI - Acid carboxypeptidase deficiency in galactosialidosis. AB - Carboxypeptidase activity with an optimal pH at 5.7 was found to be deficient in cultured lymphoblastoid cells and skin fibroblasts from 16 galactosialidosis patients of Japanese origin. The amounts of residual enzyme activities did not correlate with clinical phenotypes (early infantile and juvenile/adult). Four parents of the patients from different families showed enzyme activities at an intermediate level between the patients and normal controls. It was concluded that this enzyme deficiency is closely connected to the genetic defect of "protective protein." Further characterization with various protease inhibitors indicated that the enzyme deficient in galactosialidosis cells is a serine carboxypeptidase with histidine and cysteine residues at or near the active site. PMID- 1920916 TI - Gene mapping of human bilirubin UDP-glucuronosyl transferase on 1q21-q23 by a cell sorter and in situ hybridization. AB - The human liver bilirubin UDP-glucuronosyl transferase (bilirubin UDPGT) [EC 2.4.1.17] is responsible for the enzyme deficiency in Crigler-Najjar syndrome and/or Gilbert's syndrome. The UDPGT, former shows severe jaundice resulted from a complete absence of bilirubin while the latter has a mild manifestation due to a reduction of the enzyme activity. The gene locus of bilirubin UDPGT was mapped to chromosome 1 by spot-blot hybridization using a cell-sorter, and its regional locus was assigned to 1q21-q23 by high resolution in situ hybridization. PMID- 1920918 TI - Estimation of ages from racemization of an amino acid in teeth--assessment of errors under various experimental conditions. AB - In order to estimate ages of corpses more accurately from racemization of an amino acid (aspartic acid) in the dentine of teeth, errors resulting from various experimental conditions were assessed. The factors included for evaluation were: the sample weight, time and temperature of hydrolysis, concentration of hydrochloric acid, and the volume of the hydrochloric acid solution, each of which might have effect on resulting errors. This study revealed that alteration of the sample weight did not change the D/L ratio and that the estimated age remained constant as long as the sample weight was within the range of 3 mg and 50 mg. However, with the remaining factors, the D/L ratio changed with the alteration of conditions. The correlation can be represented by a straight line in a graph, which is a sign of the first order reaction. The coefficients of correlation were between 0.972 and 0.999, indicating their extremely high correlation with the D/L ratio. The errors expressed in estimated age values per unit of variables were: 0.02 years/min. for a time (min.) of hydrolysis; 1.5 years/degrees C for temperature of hydrolysis; 0.5 years/0.1 N (normal) for concentration of hydrochloric acid; and 0.6 years/ml for the volume of hydrochloric acid solution. Consequently, the temperature of hydrolysis was found the most influential. Alteration of values of the other four factors did not largely affect the estimation. PMID- 1920917 TI - DNA analysis of a patient with two different marker chromosomes using Y-specific DNA probes. AB - A female patient with unilateral gonadal dysgenesis was a mosaic for three cell lines, 45,X/46,X, + marI/46,X, + marII, including two different marker chromosomes. DNA analysis using 17 Y-specific DNA probes revealed that each marker consists of different segments of the Y chromosome. PMID- 1920919 TI - [Metabolism and toxicity of n-pentane and isopentane]. AB - n-Pentane and isopentane have a wide range of use, for example, for cleaning precision machinery, extracting essence and oil, and as liquid fuel for now very popular disposable lighters. They are contained in liquefied petroleum gas and natural gas as trace constituents. In our present experiments, we studied the metabolism and toxicity of these n-pentane and isopentane metabolites. Male mice of ICR strain were exposed to about 5% n-pentane for one hour while the oxygen in the environmental air was maintained at about 20%. Then their blood and liver tissue were collected and analyzed by means of GC and GC-MS. The metabolites thus obtained were 2-pentanol, 3-pentanol and 2-pentanone. The same procedure was repeated with isopentane; 3-methyl-2-butanol, 2-methyl-2-butanol and 3-methyl-2 butanone were detected as the resultant metabolites. In the presence of the NADPH generating system liver microsomes were made to react to the substrate of saturated n-pentane or isopentane aqueous solution at 37 degrees C for one hour. As a result, the same metabolites were produced as obtained in the exposure experiment. It was therefore suggested that n-pentane and isopentane were metabolized chiefly by liver microsomes. Male mice of ICR strain were fed with 80 mg/kg b.w. of phenobarbital for consecutive four days and exposed to n-pentane or isopentane for one hour. This resulted in an increase in the amount of 2-pentanol and 2-pentanone in the n-pentane inhalation and 2-methyl-2-butanol in the isopentane inhalation experiment. The toxicity of each metabolite was studied on cultured cells. The metabolites were individually mixed with HeLa S3 cell suspension, incubated for three days, and their concentration which inhibited the growth of cells by 50% (IGC 50) were compared. It was demonstrated as a result that the IGC 50 for any of the metabolites was lower than that for methanol, ethanol or acetone used as control. PMID- 1920920 TI - [Paternity test with single locus DNA probes]. AB - Seven kinds of DNA probes recognizing hypervariable DNA loci were applied to 28 cases of paternity test, involving two cases in which the putative fathers had died. The combinations of probe and restriction enzyme are as follows; MR24/1 HinfI, 3'Globin-PvuII, Ha-ras-PvuII, Mucin-PvuII, D2S44 (pYNH24)-MspI, D17S30 (pYNZ22)-MspI, D1S57 (pYNZ2)-RsaI. The reported number of the alleles are 37, 39, 5, 10, 33, 15, and 5, respectively. Those probes lie on different chromosomes except D1S57 on 1p and Mucin on 1q21. Exclusion probability (EP) and paternity index (PI) were calculated from the allele frequencies in Japanese population reported by Yokoi et al. Cumulative EP from 7 DNA probes was 0.999932, and cumulative PI ranged from 7.3 X 10(6) to 947. Also, cumulative EP from 17 kinds of conventional blood group markers (CBGM) was 0.9776, and cumulative PI ranged from 1290 to 0.11. Total EP from 7 DNA probes and CBGM was 0.999998478. Cumulative PI from 7 DNA probes were 5 to 2,000,000 times higher than that from CBGM. The single locus hypervariable DNA polymorphisms are considered to be informative for paternity test. PMID- 1920921 TI - [Clotting and fibrinolytic activities in acute alcoholic golden hamsters with or without ether anaesthesia]. AB - Fluid cadaveric blood is generally known as a characteristic of sudden death. However, it has been reported that soft blood clots have been observed in a number of cases of sudden death after alcohol drinking. Such a tendency was also recognized on autopsy cases in our laboratory. This study was carried out to reveal the effects on clotting and fibrinolytic system in golden hamsters under acute alcohol intoxication. Furthermore, the influences of ether anaesthesia were also observed. Activities of clotting and fibrinolytic factors were measured with fluorogenic peptide substrate. Prothrombin and factor X activities began to decrease 1 hr after administration of alcohol. But thrombin-like and factor Xa like activities significantly increased after 1 hr and then returned to the initial value 4 hr after administration. Plasminogen activity began to decrease 1 hr after administration, whereas plasmin-like and t-PA-like activities increased after 1 hr and returned to the initial values or decreased after 4 hr. These results show that under acute alcohol intoxication clotting and fibrinolytic factors (prothrombin, factor X and plasminogen) in golden hamsters were converted temporarily to their active forms (thrombin, factor Xa and plasmin). No influence of only ether anaesthesia on clotting and fibrinolytic activities was observed. At 1 hr after administration of alcohol some effects of ether anaesthesia on prothrombin, prekallikrein and kallikrein were observed and then were not observed after 4 hr. But it seems that the influence of ether anaesthesia on clotting and fibrinolytic activities was negligible in the process after alcohol consumption. PMID- 1920922 TI - Individual identification by VNTR analysis using minisatellite DNA probe to distinguish variable alleles at a single locus. AB - Variable number of tandem repeat analysis using a ministatellite DNA probe pYNH24 to distinguish variable alleles at a single locus was applied to forensic analysis of DNA extracted from a murder and body abandonment specimen. Two bands detected by pYNH24 correspond to identical DNA from both the upper and lower halves of a separated body, suggesting that these halves were from the same body. PMID- 1920924 TI - ABO grouping of highly-dilute blood by the absorption-elution technique using nitrocellulose beads--application to a casework investigation. AB - This paper reports a homicidal case in which the absorption-elution technique using nitrocellulose beads as immunoadsorbents was successfully applied to ABO grouping from highly-diluted blood. A 21-year-old man was found dead in bed while staying in a hotel. He had multiple wounds over the entire body. By autopsy the cause of death was decided to be traumatic shock. The victim's blood group was A. A bucket filled with faint-colored water was found at the scene. By means of the absorption-elution technique using nitrocellulose beads the water was grouped as B. Later, a 32-year-old man staying in the hotel together with the victim was suspected and arrested. The suspect's blood group was B. He confessed that he had injured himself in the hands with a knife during the struggle and washed them in the water. PMID- 1920923 TI - [A case of suicide suspected of poisoning from taking some agricultural chemicals]. AB - Forensic toxicological examination was performed on a person who was suspected of poisoning by Azomite emulsion (an acaricide), Roundup (a herbicide) and/or unidentified agricultural chemical and died after 4 days. In Japan, production of Azomite emulsion has been stopped since 1973. The unidentified agricultural chemical was identified as an agricultural chemical containing malathion, an organo phosphorous compound, by analyzing with gas chromatograph-mass spectrometer (GC-MS). When the person's serum was qualitatively analyzed with GC MS, aramite and azoxybenzene, effective components of Azomite emulsion, were detected but not glyphosate, effective component of Roundup, and malathion. And so, quantitative analysis of aramite and azoxybenzene were performed with mass fragmentography. Aramite and azoxybenzene concentrations in the serum obtained at about 9 hours after he took Azomite emulsion were 5.20 micrograms/ml and 112 micrograms/ml, respectively. Only trace amounts of them were, however, detected in the serum obtained at about 3.5 days after that. Both aramite and azoxybenzene existed significantly in liver of the corpse, and their concentrations were 12.0 micrograms/g and 254 micrograms/g, respectively. Relatively large amounts of them were also deposited in the kidney. Severe liver and kidney disorders shown in this case were considered to be mainly induced by deposits of aramite and azoxybenzene in the liver and kidney. Also in the future, poisoning by agricultural chemicals that productions have been stopped like Azomite emulsion may happen. Therefore, it may be necessary for forensic toxicologists and medical doctors in emergency hospitals to try to be able to cope promptly with such poisoning cases. PMID- 1920925 TI - Demonstration of hemoglobin in the kidney of battered children. AB - We examined specimens of renal tissue taken from 40 cadavers of children (18 battered and 22 non-battered children) by an immuno-peroxidase technique using anti-human hemoglobin (Hb) or anti-human myoglobin (Mb) antiserum. Hb was detected in the proximal tubular cells of the kidney of six battered children who had sustained severe or moderate external injuries, whereas Mb was not found. In contrast, Mb was detected and Hb was not found in the renal tubules of one child who had died from a traffic accident. In other cases including 13 cases of children who died from a sudden bout of physical violence or some other impulsive act and 4 cases of children who had died from malnutrition, neither Hb nor Mb was found in the kidney. Our findings appear to indicate that large quantities of Hb were released from the multiple lesions of the battered children, entered the circulation and were deposited in the kidneys. It thus seems that the immunohistochemical detection of Hb in the kidney may be useful for evidencing the extensive antemortem bruises which are often found in battered children. PMID- 1920926 TI - The identification of human semen by a chemiluminescent assay of choline. AB - A method for proving the presence of semen has been established by utilizing chemiluminescence for an assay of choline, a nonprotein constituent of semen, and medicolegal testings were carried out to evaluate its effectiveness. The sensitivity of this method to choline was 3 nmol/ml, and as a result of assays of the choline content in semen and in several other human body fluids and secreta, the choline level in semen was found to be 10.88-26.78 mumol/ml (mean = 16.69 +/- 4.01 mumol/ml), which was markedly higher. The choline content in semen specimens from subjects with oligospermia or azoospermia was similarly as high. Although choline was also detected in samples of certain dairy products, vegetable juice, and fruit juice, whose stains are almost indistinguishable from semen to the naked eye, the choline content in these specimens was much lower than in semen. Further, even when human semen specimens were heated to 100 degrees C for 30 min and seminal stains were heated to 200 degrees C for 30 min, the choline content still retained 71.6% and 66.9% of the pre-heating value, respectively. As for specimens of semen and seminal stains that were stored at room temperature for 12 months, about 1/3 and 1/2 of the original choline level were detected, respectively. Also, the presence of intravaginal drugs was shown to have no large influence on the detection of choline. Choline even could be detected in aged seminal stains stored for 11 years, so that the presence of semen was demonstrated. Finally, the presence of semen in the vaginal contents, collected on medicolegal autopsy, could also be demonstrated by the detection of choline. Thus utilizing chemiluminescence for detecting choline is considered useful for establishing medicolegal proof of the presence of semen. PMID- 1920927 TI - Quantitation of histamine by planimetry of latex agglutination-inhibition results. AB - A new immunologic method to measure histamine concentration in blood is described. The method is based on the planimetric measurement of the agglutinated and precipitated area of heavy latex particles on a microtiter plate. The sensitivity of the assay was 0.1 ng/ml (= 1 nM) for histamine, and the coefficients of variation were 0.43-8.8% at 7 different concentrations (n = 4). No cross-reactivity occurred with histidine, 1-methyl histamine or norepinephrine. A good correlation with the radioimmunoassay was obtained for rabbit blood, in which histamine was released either by immunogen stimulation or injection of compound 48/80 (r = 0.977, n = 26). The procedures involved in this assay method are simple and can be completed within 4-6 hours. These results indicate the usefulness of the method for forensic medical tests and/or other clinical medical tests. PMID- 1920928 TI - Postmortem changes of ingested thinner components in tissues. AB - Postmortem changes of thinner components in body tissues were examined in rats, orally given 1 ml of standard thinner solution, which was prepared by mixing toluene, ethyl acetate and isobutanol in the proportion of 8:1:1. Analysis was made by gas chromatography combined with the head space method. Three thinner components and ethanol, a metabolite of ethyl acetate, were detected in the gastric contents of all rats up until 48 hours after death. An increase in the concentration of toluene was found in the blood, lung, kidney, liver, brain and abdominal muscle with the lapse of time. On the other hand, no changes were observed in the thigh muscle throughout the 48-hour period. Isobutanol showed a similar increasing pattern to toluene, with little or no changes in the brain or in the thigh muscle. Ethyl acetate was not detected in any tissues throughout the study but it was found in the gastric contents. The results indicate that every thinner component ingested, gradually diffuses into the surrounding tissues through the stomach wall after death, and that only muscle tissue remote from the abdominal cavity, together with the gastric contents, should be analyzed for a correct diagnosis of thinner ingestion. PMID- 1920929 TI - A differential study between antemortem bleeding and a postmortem infiltration of hemoglobin. AB - In a differential study to distinguish antemortem bleeding from a postmortem infiltration of hemoglobin, glycophorins, a component of the erythrocytic membrane, were extracted from two experimental skin tissue models, i.e., skin samples taken on autopsy into which healthy human blood was injected, and skin samples undergoing a postmortem infiltration of hemoglobin; this extraction accomplished by utilizing an anti-glycophorin serum over set periods of time, after which differences between the two models were then evaluated. In all of the bleeding samples from day 0 to day 9, and in 40% of the 12-day-old bleeding samples, glycophorins were clearly detected qualitatively by counterimmunoelectrophoresis and by double-immunodiffusion. In the remaining 12-, 15-, and 18-day-old bleeding samples, glycophorins were only faintly detected by counterimmunoelectrophoresis. Additionally, in a quantitative study by rocket immunoelectrophoresis, the mean glycophorin value of 0-day-old bleeding samples was 118.5 +/- 5.6 micrograms per 0.5 g of tissue. Further, the recovery of glycophorins from the bleeding samples was satisfactory for up to 9 days, though after 12 days there was a rapid glycophorin decrease. In 15- and 18-day-old bleeding samples, the mean glycophorin values were 19.3 +/- 1.0 and 17.8 +/- 1.0 micrograms per 5 g of tissue, or about 16% and 15% of the 0-day values, respectively. In contrast, no glycophorins were detected in any of the hemoglobin infiltrated skin samples or our control samples at any time interval. These results suggest that a differential diagnosis between antemortem cutaneous bleeding and postmortem hemoglobin infiltration into the tissue is achievable within 9 to 12 postmortem days. PMID- 1920930 TI - [Individual identification from extremely contaminated forensic specimens by sequencing cloned mitochondrial D-loop genes]. AB - The PCR-amplified fragments of the human mitochondrial DNA were cloned, and independent clones were sequenced to identify individuals from trace amount of a composite forensic specimen originated from plural number of the individuals. The amplification of the mitochondrial DNA is suitable for forensic analysis where the specimens are highly degraded in most cases for its extremely high copy number and polymorphism as compared with the chromosomal DNA. And cloning procedure simplifies to correspond results to each individuals. Except three non related individuals out of 34 cases analysed so far who gave identical sequence, the sequence in this segment were highly specific to each individuals and this procedure was extremely beneficial in individual identification from trace amount of highly contaminated and degraded forensic specimens. PMID- 1920931 TI - [Traumatic intracerebral hemorrhage developing in the apparent course]. AB - The victim, 52 year old man, was thrust down and hit his left occiput against the concrete floor. He was hospitalised and his comatose state continued to the death. On admission, blood pressure was 212/110 mmHg and the computed tomography scan of the head showed only an extensive right subdural hematoma. But the intracerebral hemorrhages in the right frontal, temporal and parietal lobes were recognized 10.5 hours after the trauma. A subdural hematoma was evacuated by operation on the second hospital day. The intracerebellar hemorrhage also appeared 16 hours after the trauma. Blood pressure fluctuated between 160/80 and 200/110 mmHg. The photo of CT scan at 38.5 hours after the trauma showed little subdural hematoma and new intracerebral hemorrhage located in the left temporal lobe. On the third hospital day, he was equipped with a respirator and blood pressure was between 132/84 and 242/100 mmHg. The reaction of the pupils to light disappeared on the 8th hospital day. Blood pressure gradually decreased on the 9th and 10th hospital days and he died on the 11th day. Autopsy revealed a bruise in the left occiput, a linear fracture in the frontal and left parietal bones and a small amount of subdural hematoma on the surface of the right cerebral hemisphere. Cortical contusions were found in the right frontal, the both temporal and the left parietal lobes. Intracerebral hemorrhages were found in the right frontal, the both temporal and the right parietal lobes. Intracerebellar hemorrhage was also found. Cardiac hypertrophy and atherosclerosis of the aorta were recognized. We thought that small hemorrhages which were not clearly detectable by CT scan immediately after injury may have developed into massive intracerebral and intracerebellar hemorrhages due to high blood pressure after a hospitalization. PMID- 1920932 TI - [Reports on medico-legal data from the massive-investigation performed by the Medico-Legal Society of Japan--a statistical study of death by poisoning. Investigation Committee of the Medico-Legal Society of Japan]. AB - A statistical study was made on the fatal poisoning cases examined by forensic pathologists in Japan, in the period of 1975-1984. The total number of the cases was 1559:29.9% were poisoning by carbon monoxide, 10.9% by the other gases (cyanide, liquefied petroleum gas, hydrogen sulfide and freon), 10.9% by alcohol (mean blood ethanol level was 4.27 mg/ml), 9.3% by medicines (bromvalerylurea, barbiturates, chlorpromazine etc.), 9.2% related to burning (mean CO-Hb level was 47.9%), 7.4% by pesticides (organophosphate, paraquat, carbamate, chlorinated hydrocarbon etc.), 3.5% by methamphetamine and 11.2% by the others, including 4.9% by oxygen deficiency. These cases were found most frequently in winter and 41% of the victims died within 30 minutes after ingestion or inhalation. With regard to age distribution, the peak of frequency was 41 to 45 in male, and not characteristic in female. Samples were mainly the blood, urine and stomach contents, and analyzed by gas chromatography, spectrophotometry, ultraviolet spectrometry, thin-layer chromatography, atomic absorption spectrometry and gas chromatography-mass spectrometry. PMID- 1920933 TI - [Release of endothelin from isolated perfused human umbilical vein. I: Effect of ionomycin]. AB - Endothelin-like immunoreactivity (ET-LI) was directly measured in the perfusate from the isolated human umbilical vein perfused with Krebs-Ringer solution. The identity of the immunoreactive peptide was confirmed as ET-1 by high-performance liquid chromatography. The rate of release of ET-LI was 86.7 +/- 25.9 (SE) fmol during the first perfusion period of 30 min, and it remained stable at least for 4 hours. Calcium ionophore ionomycin, added to the perfusion medium (10(-7)-10( 6) M), stimulated the ET-LI release in a dose-dependent fashion; it increased the rate of release by 29.1% and 143.4% over the control at the concentrations of 10( 7) and 10(-6) M, respectively. These results taken together with previous observations of synthesis of ET in cultured vascular endothelium provide direct evidence for local generation and subsequent release of ET from vascular beds of human beings. PMID- 1920934 TI - [Treatment of latent diabetic nephropathy with ACE inhibitor alacepril]. AB - Latent diabetic nephropathy with no complication such as retinopaty and hypertension was treated with Alacepril, an ACE inhibitor. This study enrolled 10 patients with microalbuminuria ranging from 5 mg/day (5 mg/gCr) to 50 mg/day (30 mg/gCr). Histological changes due to diabetic nephropathy were confirmed by renal biopsy performed in 4 of 10 patients. All the patients were divided into 2 groups; 5 patients were given 25 mg of Alacepril for 6 months and the remaining 5 patients were employed as the control. As the results, the mean blood pressure was decreased from 92.7 +/- 9.0 mmHg to 87.3 +/- 11.3 mmHg in Alacepril group but these changes were not statistically significant. Microalbuminuria were significantly decreased from 17.33 +/- 7.82 mg/gCr to 10.43 +/- 4.14 mg/gCr during 6 months in the Alacepril group while in the control group, no significant changes were observed in blood pressure and microalbuminuria. Creatinine clearances were not significantly changed in both groups. These findings suggest that Alacepril is useful in improving microalbuminuria of latent diabetic nephropathy. PMID- 1920935 TI - [Effect of recombinant human erythropoietin on renal function in predialysis patients]. AB - To assess the effect of recombinant human erythropoietin (EPO) on renal function, the slopes of the regression lines of the reciprocal of serum Cr versus month (l/Cr) were studied in 8 pre-dialysis outpatients (2.9 ml/min. less than Ccr less than 17.0, 21.4% less than Ht less than 27.9) who had been followed for a period of 19 to 94 months. EPO was initially given 3000-6000 U (133 +/- 31 U/Kg/week) once weekly by the intravenous route and was later switched to the dose to achieve a Ht level of 30-35%. Mean Ht increased from 23.6 +/- 0.9 to 33.2 +/- 1.1%, and quality of life and exercise capacity were significantly improved in all patients. The mean slopes of l/Cr after EPO (-0.0050 +/- 0.0020) were not significantly different from the values before EPO (-0.0064 +/- 0.0010). The slopes of l/Cr were significantly decreased by EPO therapy in three patients observed for more than 17 months, however in one patient, it increased significantly during EPO treatment. There were no significant differences in the other 4 patients. The renal function at the initiation of EPO in a patient with increase slope of l/Cr had been the worst, and Ht was mildly increased from 21.4% to 24.1% and the blood pressure did not change significantly. The good effect on renal function observed in 3 patients may, in part, be due to better control of blood pressure and physical condition (including cardiac and immunological function) by the more close follow-up of the patients and the improvement of anemia during the period of EPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920936 TI - [Phagocytic activity and oxygen radicals production of neutrophils in patients with chronic renal failure]. AB - As disorders of the defense mechanism in hemodialysis (HD) patients, impairments of cell-mediated immunity have been known, but no agreement has yet been reached as to the function of their polymorphonuclear leukocytes (PMN). Thus this study was undertaken to determine the phagocytic activity and oxygen radicals production of PMN in patients with chronic renal failure (CRF). It was demonstrated that the phagocytic activity of PMN was significantly decreased in HD patients as compared with that in healthy subjects. A significant correlation was also found between phagocytic activity and FcR-positive cells of PMN in HD patients. It suggested that the FcR status of PMN might play an important role with phagocytic activity in HD patients, and the decrease of FcR-positive PMN affects the drop with phagocytic activity. Hydrogen peroxide production of prepared PMN was not significantly different for CRF patients versus healthy subjects. But in whole blood, the enhanced hydrogen peroxide production was observed in all CRF patients. And it was also demonstrated that PMN hydrogen peroxide production become strikingly enhanced when normal PMN was suspended in plasma from CRF patients. When normal renal function was restored by transplantation, hydrogen peroxide production was normalized. These results strongly suggested that the presence of the hydrogen peroxide production enhancing factor in plasma from CRF patients and the enhanced hydrogen peroxide production were specifically associated with renal dysfunction. In plasma of HD patient treated with the EVAL membrane, we measured the hydrogen peroxide production both before and after dialysis. The plasma of postdialysis showed slightly lower hydrogen peroxide production than that of predialysis in most of patients. It was also demonstrated that the plasma from CAPD patients showed a lower hydrogen peroxide production than that from other CRF patients. These results suggested that the hydrogen peroxide production enhancing factor could be considered as one of so called the middle molecules. PMID- 1920937 TI - [Effect of very low protein diet on the progression of chronic renal failure--a case report]. AB - Low protein diet has been a very important clinical manipulation to delay the progression of chronic renal failure. However very low protein diet (less than 30 g/day) is not popular because of concern about malnutrition due to protein restriction, and the difficulty and trouble in making palatable dish. A 48 year old man with chronic renal failure has been on a 20-30 g protein-restricted diet more than three years with no remarkable defect in his daily life, with adequate nutrition, and with very enjoyable and variable daily menus. The rate of progression of chronic renal failure was markedly slowed. Serum creatinine level was 6.9 mg/dl when he started the diet control and it took more than three years for the creatinine level reached to 15.5 mg/dl with no troublesome clinical findings or symptoms. For successful protein restricted dietary treatment, the following several ideas have been helpful: promoting the patient's understanding of the disease and treatment; abundant use of specifically made low protein, high caloric foods such as starch noodles and rice; adoption of creative menus for the patient; and using a free diet a few days a month. The results indicate that we have to again consider the effect of the very low protein (30-20 g/day) diet in slowing the progression of chronic renal failure without nutritional disturbance or restriction of the patient's palatability. PMID- 1920938 TI - [A case of the milk-alkali syndrome with a small amount of milk and magnesium oxide ingestion--the contribution of sustained metabolic alkalosis induced by hypertonic dehydration]. AB - We described a patient with the milk-alkali syndrome induced by the ingestion of small amount of milk (200 ml/day) and ice cream (145 g/day) and the administration of small dose of absorbable alkali (magnesium oxide 2.0 g/day) for the treatment of chronic constipation. The present case shows not only triads, i.e., hypercalcemia (s-Ca 14.3 mg/dl), metabolic alkalosis (s-HCO3- 37.4 mEq/L), and renal insufficiency (s-Cre 2.3 mg/dl) but also hypernatremia (s-Na 161 mEq/L) and hypertonic dehydration after the frequent episodes of elevated body temperature. The milk-alkali syndrome has been defined as the hypercalcemia with a metabolic alkalosis from a high amount of calcium intake and long term administration of absorbable alkali in any form, usually as calcium carbonate for the treatment of peptic ulcer. As the present case could be distinguished from any other cases previously reported with regard to the amount of calcium (0.4 g/day) and alkali (36 mEq/day) intake and the clinical situations that induced the syndrome, we compared the present case with the previous reports, calculating the amount of calcium and alkali intake from milk and absorbable alkali. After the introduction of the H2 blockers for peptic ulceration, the most cases with milk-alkali syndrome had provoked by the smaller amount of calcium than previously reported, which were associated with the treatment of relatively large amount of alkali (50-150 mEq/day), suggesting the role of sustained metabolic alkalosis for the development. In the present case the metabolic alkalosis induced by hypertonic dehydration and enhanced by absorbable alkali intake also could cause an increase of renal tubular reabsorption of calcium and a decrease of ionized calcium which might produce increased secretion of parathyroid hormone followed by vitamin D3 activation and increased Ca absorption from the gut. The metabolic alkalosis might be essential to the development of the milk-alkali syndrome without a high calcium and absorbable alkali intake. PMID- 1920940 TI - [The effect of blood pressure control on the progression of chronic glomerulonephritis associated with hypertension]. AB - It is well known that hypertension (HT) frequently develops in patients with chronic glomerulonephritis (CGN) and that HT contributes to progression of CGN. So, proper antihypertensive therapy is required in hypertensive patients with CGN. However, there is so far no consensus of optimal blood pressure (BP) level to maintain the renal function in these patients. In order to evaluate the BP control level in the patients with renal insufficiency, we investigated the transition of BP and renal function in 22 CGN patients with HT (average age 36.5 +/- 9.9 years at the first medical examination, 15 male, 7 female, total 179.5 patient-years), who receive antihypertensive therapy for more than 5 years as outpatients at the second department of internal medicine of Tohoku University Hospital between 1975 and 1990. Renal biopsy had been performed in all these patients for CGN diagnosis. During this period 7 patients came to receive hemodialysis therapy from 5 to 10 (average 7.6 +/- 2.1) years after the first medical examination. In one of these 7 patients, the rate of decline in renal function accelerated after child-birth, and one after two years interruption of treatment. The other 13 patients are currently receiving drug treatments at our hospital. As a result, in CGN patients there was an optimal mean BP (MBP) control range, that is, when MBP was controlled in this range, the rate of decline in renal function became slow, but when MBP deviated from this range it became fast (p less than 0.01). Moreover, this range changed according to the serum creatinine (SCr) concentration level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920939 TI - [Clinical study of concerning factors of decreased bone mineral content in hemodialysis patients]. AB - We investigated bone mineral content and factors related to decreased bone mineral content in maintenance hemodialysis patients. Bone mineral contents, epsilon GS/D, radius-bone mineral content (R-BMC) and L3-bone mineral density (L3 BMD), were measured with a micro densitometer, a bone mineral analyzer and a dual energy quantative CT scanner, and relative bone mineral contents (% epsilon GS/D, %R-BMC and %L3-BMD) were calculated respectively. The desferrioaxmine infusion test was carried out for diagnosis of aluminium associated bone disease, and an elevated level of aluminium (delta aluminium) was observed. There was reverse correlation between epsilon GS/D and age in female hemodialysis patients. Serum bone gla protein, alkaline phosphatase and PTH-C levels were high in cases with increased epsilon GS/D and who were receiving little medication with activated Vitamin D in maintenance hemodialysis patients. A correlation was observed between delta aluminium and total medication of aluminium hydroxide-gel. Hemodialysis patients with bone pain had long term hemodialysis, high total medication of aluminium and high aluminium. Relative bone mineral contents (% epsilon GS/D, %R-BMD) were useful for estimating bone mineral content in hemodialysis patients. Hemodialysis patients were divided in four groups by PTH-C and delta aluminium levels as follow, 1) normal, 2) aluminium associated bone disease, 3) secondary hyperparathyroidism with aluminium associated bone disease, 4) secondary hyperparathyroidism. These results indicate that secondary hyperparathyroidism, and medication with aluminium may play a role in decreased bone mineral content in hemodialysis patients, and menopause may also be an important factor in female hemodialysis patients. PMID- 1920941 TI - [A case of childhood IgA nephropathy who developed rapidly progressive glomerulonephritis in one-year clinical course]. AB - A 10-year-old girl who presented with microscopic hematuria, proteinuria and normal renal function has been followed up for the past two years. At the first examination, renal biopsy revealed focal/segmental lesions accompanying by occaisional necrosis and small crescents. Diagnosis of IgA nephropathy was given by light, electron and immunofluorescent microscopic findings. She started on the treatment with dipyridamol and was followed up for one year without any serious complications. Thereafter, she suddenly developed severe deterioration of renal function (serum creatinine 2.7 mg/dl) with nephrotic syndrome and hypertension. The second renal biopsy done at this time indicated the presence of typical crescentic glomerulonephritis with mesangial proliferation. No vasculitis was noted. She was intensively treated with steroids, anticoagulants and other medication and responded fairly well clinically. The third renal biopsy performed 5 months afterwards demonstrated marked histological improvement, but there was still present mesangial proliferation and varied degrees of sclerotic changes with fibrocellular crescents. Focal interstitial fibrosis and collapsed tubules were also seen. At present, 5 months after the last renal biopsy, she has improved much better and her serum creatinine decreased to 1.9 mg/dl, although proteinuria of 3 g/day still persists. It is suggested that only a small segmental necrosis with crescent formation in IgA nephropathy should be considered as an important indicator of disease activity in the evaluation of prognosis. PMID- 1920942 TI - [Familial systemic lupus erythematosus in mother and son]. AB - Although the etiology of systemic lupus erythematosus (SLE) is thought to be multifactorial, genetic factors may play some role in its pathogenesis. Supportive of this hypothesis are the studies of identical twins and familial cases of SLE. We describe below a family in which mother and son both developed SLE. The mother was diagnoged as SLE at age 25, and had been treated with prednisolone. In February 1989, she had massive proteinuria. The onset of the son's disease was at age 13 in 1988, when he noted erythema and photosensitivity. At admission to our hospital in 1989, he had polyarthralgia, proteinuria, positive antinuclear antibody, positive anti-DNA antibody. Both two patients had a same haplotype, HLA A2.BW61(40).DR9. Two asymptomatic members of this family were also studied, the younger son had positive antinuclear antibody and hypocomplementemia. PMID- 1920943 TI - [Membranous glomerulonephritis probably related to bucillamine therapy in two patients with rheumatoid arthritis]. AB - We describe here two patients with rheumatoid arthritis who developed nephrotic syndrome after administration of bucillamine, a novel antirheumatic drug developed in Japan. The nephrotic syndrome occurred after six months' and five months' treatment of bucillamine, respectively. The renal biopsy showed early phase of membranous glomerulonephritis (stage 1) in both patients. The first patient was a 64-year-old man who had received gold therapy for two years, and penicillamine therapy for eight months before bucillamine therapy. The nephrotic syndrome occurred after one year's cessation of the gold therapy and six months' cessation of the penicillamine therapy. The other patient, 57-year-old woman, had no history of gold or penicillamine therapy. Our experience suggests that membranous glomerulonephritis might occur in relation to bucillamine therapy. PMID- 1920944 TI - [A Phase 1 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I BMIPP)]. AB - Phase 1 study of beta-methyl-p-(123I)-iodophenylpentadecanoic acid (123I-BMIPP), a new radiopharmaceutical developed for the evaluation of myocardial fatty acid metabolism, was performed in six normal volunteers to evaluate its biodistribution and safety. After intravenous injection of 111 MBq of 123I-BMIPP, the agent accumulated to the myocardium rapidly (5.4 +/- 0.6% at 1.5 hr after injection) and was washed-out slowly (5.1 +/- 0.4% at 3.0hr). 123I-BMIPP demonstrated no significant accumulation to any specific organs other than myocardium, liver and muscle. Myocardium was clearly visualized in the planar and SPECT images obtained 30 min and 3 hrs after injection. The absorption doses from 123I-BMIPP estimated by MIRD method were lower than those from 201Tl in all organs. Neither adverse reactions nor abnormal clinical laboratory findings were found in the safety evaluation. These results suggest 123I-BMIPP is a promising agent for evaluating myocardial fatty acid metabolism. PMID- 1920945 TI - [Clinical implications of diffuse slow washout of thallium-201 in exercise stress myocardial SPECT]. AB - Clinical implications of diffuse slow washout of thallium-201 (DSWO) in exercise redistribution myocardial SPECT were studied. Thallium-201 washout rate was calculated by Bull's-eye method. DSWO was defined as having abnormal thallium-201 washout rate (less than 30% per 3 hours) in more than two thirds of each coronary artery (CA) area. OF 974 patients whose exercise heart rate exceeded 120/min, 51 (5.2%) showed DSWO and coronary angiography was performed in 43. Twenty-three patients (53%) showed triple vessel disease (3VD), 8 (19%) showed single or double vessel disease (1VD/2VD) and 12 (28%) showed normal CA. Patients with normal CA consisted of 6 patients with hypertrophic cardiomyopathy (HCM), 5 with hypertension (HT) and one with electrocardiographic abnormality only. The causes of DSWO were assessed from the history of effort angina (EA) and congestive heart failure (CHF), delayed fill-in of the perfusion defect and the ratio of lung to heart thallium-201 activity (L/M) at exercise as an indicator of the left ventricular (LV) function. High prevalence of EA (74%), high incidence of scintigraphic delayed fill-in (83%) and normal L/M suggested diffuse LV ischemia as the cause of DSWO in 3VD. On the other hand in patients with 1VD/2VD, LV dysfunction at exercise was considered as the cause of DSWO because of low prevalence of EA (13%) and scintigraphic delayed fill-in (13%) (p less than 0.01, p less than 0.005 each vs 3VD), and high L/M (p less than 0.001 vs 3VD) and high prevalence of CHF (38%, NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920947 TI - [Radionuclide assessment of left ventricular diastolic function in patients with mitral stenosis before and after percutaneous transvenous mitral commissurotomy; use of list mode method in patients with atrial fibrillation]. AB - To evaluate the effect of percutaneous transvenous mitral commissurotomy (PTMC), equilibrium radionuclide angiocardiography was performed in eight patients with mitral stenosis who had atrial fibrillation. Accurate cardiac function in patients with atrial fibrillation is difficult to assess, since the wide fluctuation of cardiac cycle makes the ventricular hemodynamics variable. A new processing algorithm was devised to make multiple gated images discriminated from a heart rate distribution histogram. We obtained about 1,000 beats data by list mode acquisition, and processed a heart rate distribution histogram. The data in the area +/- 5% of the most frequent heart rate were converted into frame mode and a representative time activity curve was derived. Mitral valve area calculated by echocardiography increased from 1.3 +/- 0.5 to 2.0 +/- 0.6 (cm2) significantly (p less than 0.01). The mean transmitral pressure gradient measured by catheterization decreased from 12.4 +/- 5.9 to 4.9 +/- 3.7 (mmHg) significantly (p less than 0.01) and the clinical symptoms improved in all patients. The change in left ventricular ejection fraction from 43 +/- 9 to 48 +/ 13 (%) was not statistically significant, but peak filling rate (PFR) derived from the time activity curve increased from 1.5 +/- 0.3 to 2.0 +/- 0.4 (EDV/sec) significantly (p less than 0.01). Thus PFR is a noninvasive parameter that can evaluate the effect of PTMC. PMID- 1920946 TI - [Evaluation of brain perfusion SPECT imaging using 99mTc-ECD]. AB - Fundamental and clinical evaluation was performed on 99mTc-ECD, a new agent for brain perfusion SPECT. Radiochemical purity reaches a plateau of approximately 98% at 30 min after reconstitution and remains stable up to 24 hours later. A biodistribution study showed approximately 5% injected dose in the brain, very slow brain washout of 5.6% per hour on the average, and rapid washout from the other organ mainly through the urinary system. Brain ECD distribution was determined within 2 min postinjection and remained stable for up to 1 hour. Three hours later, slight but significant changes in brain distribution were observed, that were relative reduction of cerebral cortical activity and gray to white matter activity ratio, and relative elevation of white matter and thalamic activities. Comparative studies of ECD images with IMP and HMPAO images revealed that radioactivity contrast between affected and unaffected areas was less prominent in ECD than in IMP in cerebral and cerebellar cortical lesions, more prominent in ECD than in IMP in striatal and thalamic lesions, and somewhat more prominent in ECD than in HMPAO in both lesions. Imaging around 1 hour postinjection seems to be more appropriate than immediate postinjection imaging because of the clearance of the extracranial radioactivity and somewhat better radioactivity contrast between affected and unaffected areas. PMID- 1920948 TI - [A comparison of measurements of serum free thyroxine concentration by equilibrium dialysis and ultrafiltration using undiluted serum]. AB - We have examined the clinical usefulness for free thyroxine (FT4) measurement by equilibrium dialysis of undiluted serum and by radio-immunoassay of T4 concentration in the dialysate (ED/RIA). The results were compared with those by ultrafiltration of undiluted serum (UF/RIA), which is believed to offer the best possible approach towards estimation of in vitro serum level of FT4. The precision with both methods was excellent. There was a high degree of correlation of FT4 concentration by both methods (r = 0.831, p less than 0.001, n = 99). FT4 concentration by ED/RIA and UF/RIA methods agreed well for hyperthyroidism, hypothyroidism, normal pregnancy, and for low T4-binding globulin concentration. In nonthyroidal illness (NTI), FT4 levels were all within or above normal for UF/ED method, while some FT4 values in low T4 syndrome were below normal for ED/RIA method. The effect of progressive serum dilution on FT4 concentration was also examined for both methods. There was no fall in FT4 concentration in sera from normal, hyperthyroid patient and in serum with low T4 syndrome for both methods, but in a serum from low T3 syndrome, there was a fall in FT4 concentration by dilution with UF/RIA method, indicating that serum dilution with ED/RIA method might underestimate FT4 concentration in some NTI sera. From these results it is concluded that the present ED/RIA method is adaptable to clinical laboratory use as a reference standard method for FT4 measurement. PMID- 1920949 TI - [Evaluation of myocardial uptake of thallium-201 in whole body scintigraphy]. AB - Whole body scintigraphy (WBS) was performed to assess the myocardial uptake in the dipyridamole (DP), exercise loading (EX) and thallium-201 (Tl-201) myocardial scintigraphy. DP-WBS was studied in 15 patients (pts), EX-WBS was studied in 17 pts and resting (RE)-WBS was studied in 20 pts. All pts had some kinds of heart disease clinically, but their myocardial scintigraphy showed no abnormal findings. DP-WBS and EX-WBS were performed both immediately (early image DP-E, EX E) and 3 hours later (delayed image EX-D, DP-D) after injection of Tl-201. RE-WBS were performed immediately (early image REST) after injection of Tl-201 only. The percent myocardial uptake, background ratio of the myocardium and washout ratio of some organs were calculated from the ROIs (region of interest) over the whole body, heart, lung, mediastinum, abdomen and thighs. The myocardial uptake of DP-E was 9.1 +/- 1.4%, myocardial uptake of EX-E was 6.3 +/- 0.8% and myocardial uptake of REST was 7.1 +/- 1.2%. The thighs uptake of DP-E was 10.4 +/- 1.1%, thighs uptake of EX-E was 25.3 +/- 2.6% and thighs uptake of EX-E was 25.3 +/- 2.6% and thighs uptake of REST was 10.1 +/- 1.5%. The percent myocardial uptake of DP-E was not only higher than that of EX-E (p less than 0.001) but also higher than that of REST (p less than 0.01). Thus, we conclude that DP scintigraphy showed clearer myocardial image than EX scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920950 TI - [Effect of white matter lesions on cerebral blood flow in asymptomatic individuals: assessment by MRI and 133Xe-CBF method]. AB - In 32 patients with asymptomatic white matter lesions (WMLs), we evaluated the age-related changes in the number of white matter lesions, cerebral blood flow (CBF), cerebrovascular resistance (CVR) and mean arterial blood pressure (MABP). CBF was measured with the intravenous 133Xe injection method. The number of WMLs in whole brain was measured by the magnetic resonance imaging. CBF decreased with advancing age (r = 0.529; p less than 0.01), while the number of WMLs (r = 0.39; p less than 0.05), CVR (r = 0.464; p less than 0.01) and MABP (r = 0.229; ns) increased with advancing age. There was a significantly negative correlation (r = -0.499; p less than 0.01) between CBF and the number of WMLs. While, CVR showed a positive correlation with the number of WMLs (r = 0.468; p less than 0.01). Multivariate regression analysis with stepwise forward selection method indicated that the number of WMLs and age were independent and negative predictors for CBF, while other factors did not. CBF decreased with a concomitant rise in CVR. On the basis of the results listed above, we assumed that ischemic damage of the white matter and/or functional suppression of distant loci due to the primary tissue damage are the best explanation for CBF reduction in asymptomatic individuals with WMLs. High resolution CBF imaging as well as evaluation of structural alterations in cerebrovascular vessels should be required to further define the mechanisms. PMID- 1920951 TI - [Characteristics of Tl-201 myocardial SPECT images of patients with coronary artery lesion of diagonal branch]. AB - Noninvasive detection of coronary artery lesion of diagonal branch is important. Utility of Tl-201 myocardial SPECT images for this purpose was studied in 9 patients with angina pectoris and 4 patients with myocardial infarction, in whom localized stenosis more than 75% was noted at diagonal branch. Position of basal margin of abnormal region in the coronal images lay between -30 degree and 30 degree and basal abnormal region was very narrow. Width of mid portion of abnormal region lay from 5 degree to 70 degree. Abnormal region due to diagonal branch was not noted in septal region. These results showed the utility of Tl-201 myocardial SPECT images for detecting coronary artery lesion of diagonal branch. PMID- 1920952 TI - [Experimental study on the mechanism of the intrapulmonary kinetics of 123I-IMP in a balloon occluded bronchus in rabbits]. AB - To investigate the mechanism of intrapulmonary kinetics of N-isopropyl-p-123I iodoamphetamine (123I-IMP), we performed lung scanning with 123I-IMP in 13 rabbits in which a unilateral bronchus was occluded by a balloon catheter. In 9 rabbits, on the delayed distribution images, an abnormal accumulation of 123I-IMP was detected in the hypoperfusion area of the peripheral lung field of the occluded bronchus, which was detected on lung perfusion images with 99mTc-MAA. Comparison of early (a summation image during 20 seconds immediately after injection) and delayed (a summation image from 70 to 90 minutes after injection) distribution images confirmed that during this period, 123I-IMP accumulated in the area of reduced distribution of 123I-IMP. Moreover, at the site of abnormal accumulation, washout of 123I-IMP from the lung was delayed compared with that in the normal lung field. We find this experimental study is similar to the results in 63 clinical cases, which we have reported previously, and confirm that pulmonary arterial perfusion, especially hypoperfusion, influences the intrapulmonary kinetics of 123I-IMP. PMID- 1920954 TI - [The functional relationship between the cerebral cortex and deep brain areas in normal individuals]. AB - Recent PET or SPECT studies have demonstrated a reduction of blood flow and metabolism in the cortex ipsilateral to a deep-seated lesion, and in the thalamus and/or basal ganglia ipsilateral to a cortical lesion. A close relationship between the cerebral cortex and deep areas of the brain has been shown in pathological conditions, presumably because of functional interconnections between the cortex and deeper area. The present study was designed to investigate the relationship of cerebral blood flow in the cerebral cortex to that in the deep gray matter including the basal ganglia and the thalamus in normal subjects. Twenty-two healthy subjects were studied using SPECT with N-isopropyl p[123I]iodoamphetamine while in a resting state. The asymmetry index (AI) of blood flow in both the cerebral cortex and deep gray matter was calculated as follows; AI = (R-L)/(R+L)/200 (%) (R: right side, L: left side). The AI in deep gray matter was significantly correlated with the AI values in the upper frontal cortex (r = 0.54, p less than 0.01), and parietal cortex (r = 0.58, p less than 0.01), as well as the mean cortical hemispheric AI (r = 0.48, p less than 0.05). Our results suggest the existence of a functional relationship between the cerebral cortex and deep areas not only in pathological conditions but also in the resting state in normal subjects. This functional relationship is likely to be mediated by neuronal mechanisms through the projectional fiber connections between the cortex and the deep gray matter. PMID- 1920953 TI - [123I-IMP per-rectal portal scintigraphy in a patent ductus venosus: a case report]. AB - Portosystemic shunt is most frequent in portal hypertension associated with hepatic cirrhosis, meanwhile there are uncommon cases which have congenital portosystemic shunt. Recently we have encountered a patient with ductus venosus definitely diagnosed by angiography. In this patient, we performed a portal scintigraphy with 123I-IMP per-rectal administration in order to evaluate the portosystemic circulation. At the early phase of the study, the scintigraphy showed only the pulmonary uptake of 123I-IMP, and the liver was not revealed. Such findings in congenital anomalous cases of portosystemic shunt without hepatic parenchymal damage like this case can be similar to those in cirrhotic patients. In conclusion, this method was useful in evaluation of the portosystemic circulation, and helpful in determining therapeutic procedures for portosystemic circulation disorders. PMID- 1920955 TI - [Lymphoscintigraphy with 99mTc-DTPA-HSA: detection of metastases to iliopelvic lymph nodes]. AB - The purpose of this study was to evaluate 99mTc-DTPA-HSA as an iliopelvic lymphoscintigraphic agent in 5 normal volunteers and 10 patients with metastases of malignant tumors (cancer, 9; and malignant lymphoma, 1) to the iliopelvic lymph nodes. The subjects underwent intradermal injection of 185 MBq of 99mTc DTPA-HSA into digital web spaces of the feet. Massage was applied at the injection sites for 30 sec; the subjects then walked around for 2 min. Whole-body scintigrams were obtained 5 min after injection. The whole-body scanning speed was 20 cm/min. The tracer transport was prompt. Within 15 min after injection, the tracer reached the termination of the thoracic duct in all normal volunteers. Normal whole-body images of excellent quality delineated the lymph nodes and channels almost without background radioactivity. The images of 9 patients with metastases of cancer showed clearly the following abnormal patterns: a) obstruction of lymphatic system (5/9, 55.6%); b) absence of visualization of the thoracic duct (44.4%); c) decreased uptake in lymph nodes (88.9%); d) visualization of collateral circulation (44.4%); e) tracer extravasation into more proximal soft tissue (22.2%). The image in the patient with malignant lymphoma showed increased uptake in the enlarged lymph nodes in addition to the all abnormal findings mentioned above. We concluded that 99mTc-DTPA-HSA is an excellent radiopharmaceutical for iliopelvic lymphoscintigraphy. PMID- 1920956 TI - [New analysis algorithm for regional cerebral blood flow and partition coefficient with dynamic SPECT and N-isopropyl-p-[123I]iodoamphetamine: graphical plot method]. AB - We developed a new analysis algorithm based on multiple-time graphical plot to estimate the regional cerebral blood flow and partition coefficient using dynamic SPECT and N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). By assuming the 2 compartment model of the kinetic for 123I-IMP, we derived a linear relationship between the ratio of the tissue activity concentration at the times to the time integral arterial concentration at the respective times (formula; see text) and the ratio of the time-integral tissue concentration to the time-integral arterial concentration (formula; see text), and demonstrated that the Y-intercept and X intercept of the plot line represent the regional cerebral blood flow (K1) and partition coefficient (lambda), respectively. The slope of the line represents a clearance constant k2. The present method was applied to data on four normal subjects measured by dynamic SPECT. Values of the K1 and lambda for the gray matter were obtained 40.8 +/- 6.5 ml/100 g/min and 28.8 +/- 5.3 ml/g, respectively, and the corresponding values for the white matter were 29.1 +/- 4.7 ml/100 g/min and 28.1 +/- 7.1 ml/g. The new method enabled a rapid estimation of both K1 and lambda. PMID- 1920957 TI - Manifestations of temporary symptoms during endoscopic variceal sclerotherapy using thrombin as a sclerosant. AB - We performed 93 sclerotherapy sessions on liver cirrhosis patients with recurrent variceal bleedings. In each session, hypertonic glucose, thrombin and 1% polidocanol were consecutively injected into the varices, and changes in the hemostatic system were examined in relation to the symptoms observed during the treatment. Patients underwent sclerotherapy with no complaints in 62 (67%) sessions, and complained of slight symptoms of general fatigue and headache in 19 (20%). In the other 12 (13%) sessions, the procedure was discontinued due to marked manifestations of these symptoms. All symptoms were temporary and disappeared completely after the procedure. These temporary symptoms were closely related to changes in coagulation tests similar to those of disseminated intravascular coagulation, which were observed just after the treatment. Possible activation of the renal kallikrein-kinin system following injection sclerotherapy was also demonstrated. PMID- 1920958 TI - A coordinate axis transformation study of spatial QRS loop in hypertrophic cardiomyopathy. AB - To obtain an overall view of the QRS loop on vectorcardiograms (VCG) of hypertrophic cardiomyopathy (HCM), the coordinate axis was transformed using the resolver method. The morphological features and planarity of the loop were compared with hypertrophic patterns and hypertensive heart disease (HHD). The subjects in the present study included 30 normal individuals, 40 patients with HCM and 30 with HHD. The HHD group was selected from patients showing left ventricular hypertrophy on VCG similar to that of HCM patients. The HCM group showed significantly greater values than the HHD group in the thickness/length ratio, which represents the planarity of the spatial QRS loop. The above finding suggests that the HCM group had greater deformation in the QRS loop than the HHD group. This may provide a useful indicator for the differential diagnosis of the two diseases. PMID- 1920959 TI - Thyrotropin releasing hormone (TRH)-induced release of 7B2 (neuroendocrine polypeptide) in vivo and in vitro using adenoma cells of a patient with acromegaly. AB - We demonstrated TRH-induced release of 7B2 (a neuroendocrine polypeptide) in vivo and in vitro (somatotroph adenoma cells) in a patient with acromegaly. The mean basal plasma 7B2 and growth hormone (GH) levels before operation were 142.8 +/- 3.2 ng/l and 52.4 +/- 1.6 micrograms/l (mean +/- SEM), respectively and these levels significantly rose after an i.v. administration of 500 micrograms of thyrotropin releasing hormone (TRH). After the transsphenoidal adenomectomy, the basal level of plasma GH was restored to the normal level and that of plasma 7B2 was slightly decreased. In addition, TRH-induced response of plasma 7B2 and GH disappeared post-operatively. In a primary culture of somatotroph adenoma cells obtained at surgery, TRH significantly induced secretions of both 7B2 and GH. Immunohistochemical studies showed the positive 7B2 and GH immunoreactivities in somatotroph adenoma cells. These findings strongly suggest that the somatotroph adenoma cells in this case produced and released 7B2 concomitant with GH. PMID- 1920960 TI - Myocardial metastasis from primary lung cancer: myocardial infarction-like ECG changes and pathologic findings. AB - Myocardial metastasis from neoplastic disease is often clinically unapparent, and very difficult to diagnose. Of 151 consecutive autopsies of lung cancer patients, cardiac metastases were found in 67 patients (44.4%). Myocardial metastasis was found in only 8 patients (11.9%). ECG of patients with myocardial metastasis revealed ST-T wave changes and various types of arrhythmia. ST-T wave changes were observed in 4 with myocardial metastasis, and in 6 without myocardial metastasis (pericardial metastasis alone). ST-T wave changes is not a specific finding of myocardial metastasis. Two very rare cases with myocardial metastasis showing progressive ST segment elevation with a QS pattern are presented. The appearance of ST segment elevation with a QS pattern in clinically stable lung cancer patients without cardiac symptoms suggestive of myocardial injury indicates the possibility of myocardial metastasis. Myocardial metastasis is often elusive, thus careful observation of ECG changes is of primary importance for the antemortem diagnosis. PMID- 1920961 TI - Thyrotoxic periodic paralysis complicated with primary aldosteronism. AB - A 35-year-old man presented with acute onset of bilateral lower extremity weakness after ingesting a large amount of carbohydrates. Laboratory investigation revealed severe hypokalemia (1.9 mEq/l) and hyperthyroidism. The patient also exhibited primary aldosteronism due to a left adrenal adenoma. As a diagnostic tool, paralysis with hypokalemia (2.8 mEq/l) was induced with a glucose infusion. After treatment with methimazole, there were no further episodes of paralysis and subsequent induction of paralysis with glucose was impossible, though primary aldosteronism persisted. These findings indicate that hyperthyroidism played a major role in the development of periodic paralysis, while primary aldosteronism apparently increased the patient's vulnerability to paralytic attacks. PMID- 1920962 TI - Leukotoxin, 9, 10-epoxy-12-octadecenoate: a possible responsible factor in circulatory shock and disseminated intravascular coagulation. AB - We previously demonstrated that neutrophils biosynthesize the Iinoleate epoxide, 9,10-epoxy-12-octadecenoate, from linoleate and hydroxyl radical. This epoxide is highly cytotoxic, and has been termed leukotoxin. We detected leukotoxin in plasma from two patients with infectious endocarditis and circulatory shock. Maximal leukotoxin levels were 580 nmol/ml and 880 nmol/ml, respectively. The leukotoxin levels were affected by hemodialysis or hemofiltration. Disseminated intravascular coagulation was confirmed by blood coagulation studies in these two patients. Leukocytosis was also observed in these patients. In contrast, leukotoxin was not detected in plasma of normal volunteers. Accordingly, leukotoxin synthesized by recruited neutrophils might be a contributory factor in circulatory shock. PMID- 1920963 TI - Magnetic resonance imaging in diagnosis and follow-up of minimal thyroid ophthalmopathy. AB - We report a case of minimal thyroid ophthalmopathy treated with intravenous methylprednisolone, in which precise identification of the involved muscle was possible with the use of surface coil magnetic resonance (MR) imaging. Intravenous methylprednisolone was more effective than the oral prednisolone as judged by orbital MR imaging. MR imaging is one of the useful tools in the diagnosis and assessment of treatment in this field. PMID- 1920964 TI - Masked Cushing's disease in an aged man associated with intraventricular hemorrhage and tuberculous peritonitis. AB - A 77-year-old man complained of headache, dizziness and tactile hallucination. Based on those clinical signs and the findings of computed tomography scanning and magnetic resonance imaging, he was diagnosed as having pituitary adenoma. Clinical signs and symptoms of Cushing's disease had not been apparent because of the occurrence of the disease at an old age. An increase in serum cortisol and adrenocorticotropic hormone indicated the presence of Cushing's disease. Physical findings obtained thereafter were also compatible with the disease. While the patient was being prepared for surgery, pituitary apoplexy and intraventricular hemorrhage occurred. Massive ascites appeared as a result of tuberculous peritonitis. In spite of treatment for these complications, his general condition progressively deteriorated and he died 39 days after the intraventricular hemorrhage. This case presents the difficulty in the treatment of masked Cushing's disease in the elderly population. PMID- 1920965 TI - Crescentic glomerulonephritis associated with renal amyloidosis. AB - A case of crescentic glomerulonephritis associated with renal amyloidosis is reported. A 62-year-old woman with a 6-yr history of rheumatoid arthritis developed rapidly progressive glomerulonephritis associated with renal amyloidosis and crescent formation. Amyloid protein was positively stained with anti-AA antibody and its fibrils were demonstrated by electron microscopy. In connection with epithelial cell proliferation in the capsular space, destruction of the capillary basement membrane was observed at the sites where amyloid fibrils were accumulated, whereas glomerular deposition of immunoglobulin and complement was not detected. It is conceivable that the destruction of the glomerular tufts induced by amyloid deposition may be responsible for the crescent formation. PMID- 1920966 TI - Adult-onset Still's disease: hepatic involvement and various serum markers relating to the disease activity. AB - A 53-year-old woman was admitted to our hospital due to high fever, arthralgia and skin rash. Main laboratory data included the following: WBC 17,100/mm, GOT 58 U, GPT 47 U, LDH 1,510 U, ferritin 19,000 ng/ml, adenosine deaminase 79.1 U/l. She was diagnosed as having adult-onset Still's disease. Aspirin (3.0 g/day) and prednisolone (40 mg/day) were administered. All the symptoms and laboratory data improved rapidly. Adenosine deaminase, ferritin, and LDH are considered to originate mainly from the liver. Liver injury in this disease may be a primary lesion, and various serum markers may be associated with the liver abnormalities. PMID- 1920967 TI - A case of Behcet's disease with a rapidly enlarging aneurysm in the common carotid artery. AB - A 16-year-old boy had incomplete Behcet's disease with common carotid artery aneurysm and an ulcer in the transverse colon. To our knowledge, this complication in the carotid artery has been previously reported in only 6 cases. Arterial repair and high-dose corticosteroid therapy (pulse therapy) were successful. PMID- 1920968 TI - Vitiligo and chronic photosensitivity in human immunodeficiency virus infection. AB - A 56-year-old man was admitted with hemiparesis and shortness of breath. He was positive to human immunodeficiency virus (HIV) antibody and was diagnosed as acquired immunodeficiency syndrome (AIDS) with Kaposi's sarcoma and pneumocystis carinii pneumonia. He developed chronic photosensitivity and vitiligo preceding the onset of the AIDS-related complex (ARC). Association of the two skin lesions with HIV infection is very rare. Although the role of HIV infection in these skin lesions is not significant, the immunological responses in the early course of HIV infection may have contributed to the development of both of these skin lesions. PMID- 1920969 TI - Self-management of nocturnal respiratory insufficiency with a portable ventilator "Pneu-PAC" by an amyotrophic lateral sclerosis patient. AB - A 76-year-old man with amyotrophic lateral sclerosis was admitted to our hospital because of progressive exertional dyspnea (PaCO2 = 68.5 torr, PaO2 = 62.5 torr). He was put on mechanical ventilation, and thereafter sleep apnea of a central type was recognized. After improvement of general conditions, a portable ventilator "Pneu-PAC" was used for the self-management of nocturnal respiratory insufficiency. A portable ventilator might be of clinical benefit for the management of a patient with neuromuscular disorder whose activities of daily living are still functional. PMID- 1920970 TI - Association of mixed connective tissue disease, Sjogren's syndrome and autoimmune hepatitis: report of a case. AB - A 51-year-old female was admitted to the hospital due to liver dysfunction. She had suffered from arthralgia, Raynaud's phenomenon, dry mouth and dry eyes. Laboratory data showed positive LE cells and anti-RNP. The diagnosis of mixed connective tissue disease (MCTD) was made according to the criteria of the international symposium on MCTD and Antinuclear Antibodies (August 1986, Tokyo). Liver biopsy showed chronic active hepatitis. The results of sialography, lip biopsy and rose-bengal test were compatible with Sjogren's syndrome (SjS). This is the report of a rare case with MCTD associated with SjS and autoimmune hepatitis. PMID- 1920971 TI - Dramatic recovery from neurological deficits in a patient with central pontine myelinolysis following severe hyponatremia. AB - A 28-year-old woman developed central pontine myelinolysis (CPM) following severe hyponatremia. Radiological examinations demonstrated a characteristic pontine lesion of CPM. Her neurological symptoms (drowsiness, emotional lability, dysarthria, dysphagia, and quadriparesis) were improved dramatically by treatment with thyrotropin-releasing hormone (TRH) and rehabilitation. However, results of repeat computed tomographic (CT) scans of the brain remained unchanged. This case therefore suggests that TRH may be beneficial for the treatment of CPM, and that CT findings appear to be a limited prognostic indicator for CPM. PMID- 1920972 TI - Acute febrile mucocutaneous lymph node syndrome (Kawasaki disease) in adults: case report and review of the literature. AB - A 25-year-old female meeting all six criteria for Kawasaki disease is reported. A total of 22 reported cases of adult Kawasaki disease, including the present case, are reviewed. In adult Kawasaki disease, arthralgia, gastrointestinal complications and hepatic dysfunction are seen more frequently than in childhood cases. Cardiac complications are rarely seen in adult Kawasaki disease. Two cases have been positive for anti-nuclear antibody (ANA). The present patient had increased levels of serum IgE and was positive for ANA, suggesting involvement of an immune mechanism. Adult Kawasaki disease is rare but appears to be on the increase; internists treating adults must be aware of this disease. PMID- 1920973 TI - [The metabolism of peptide leukotrienes in the lung may affect their coronary vasoconstrictive effect in anesthetized dogs]. AB - The deteriorative effect of peptide leukotrienes (LTs) on the coronary circulation are well known. On the other hand, it has been recognized that some of these prostanoids are metabolized in the pulmonary vascular bed. To clarify the influence of the metabolism of LTs in the lung on their effects to the coronary circulation, we compared the changes of coronary circulation parameters by leukotriene D4 (LTD4) and C4 (LTC4) administered (5 mcg/kg) into the right atrium (RA) and the left atrium (LA) in 8 mongrel dogs. After the administration of LTD4 and LTC4, significant reduction of coronary blood flow (LTD4-RA 65.8 +/- 3.4%, LTD4-LA 54.8 +/- 2.3%, LTC4-RA 64.3 +/- 3.9%, LTC4-LA 66.9 +/- 3.7%) and elevation of coronary vascular resistance (LTD4-RA 130.5 +/- 8.2%, LTD4-LA 157.3 +/- 6.1%, LTC4-RA 138.7 +/- 8.0%, LTC4-LA 129.5 +/- 10.1%) were recognized. The effect of LTD4, administered into the left atrium was significantly greater than that administered into the right atrium (p less than 0.05). The difference between right and left atrial administration was not statistically significant, although a tendency for the effect to be greater with right atrial administration than left was recognized. The LTC4 concentration in aortic blood measured by radioimmunoassay was significantly lower in right atrial administration than left (p less than 0.05). These results suggested that LTD4 was metabolized and inactivated in the lung during its passage through the pulmonary circulation, and LTC4 was not only inactivated but also converted to LTD4 and activated in the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920974 TI - [The effect of aging on respiratory muscle function]. AB - To elucidate the effect of aging on respiratory muscle function, the authors performed respiratory muscle function tests in 116 normal subjects. Respiratory muscle function was evaluated with maximal expiratory mouth pressure at the TLC level (PEmax) and maximal inspiratory mouth pressure at the RV level (PImax). PEmax and PImax in both sexes showed significant correlations with age. PEmax in males was significantly higher than that in females (123.6 +/- 29.7 cmH2O and 79.0 +/- 21.1 cmH2O, p less than 0.01, respectively). PImax in males was also significantly higher than that in females (98.4 +/- 26.0 cmH2O and 71.9 +/- 26.4 cmH2O, p less than 0.01, respectively). PEmax correlated significantly with TLC, and PImax showed a significant inverse correlation with RV/TLC. Furthermore, there was a significant inverse correlation between RV/TLC and age. Our data suggest that inspiratory muscle weakness in aging may be responsible for the increase in RV/TLC. PMID- 1920976 TI - [Changes in cardiopulmonary functional reserve after thoracic surgery assessed by treadmill exercise test]. AB - The authors evaluated the effect of thoracic surgery on cardiopulmonary functional reserve using a three-minute incremental test on treadmill before and after operation in 148 patients undergoing thoracic surgery. Patients were divided into two groups according to the presence or absence of respiratory symptoms during the exercise test. In all patients, the number of cases with hypoxemia induced by exercise test increased postoperatively including all cases with pneumonectomy. The number of patients who halted the test because of respiratory symptoms (Group A) increased after operation (45 cases before (30.4%), 82 cases after (55.4%)). Most of them showed at least 10 Torr lower PaO2 levels than their basal levels during exercise. Before operation, patients in Group A (n = 45) showed significantly lower FEV1.0% than those who halted the test because of other symptoms (Group B, n = 103) (68.0 +/- 12.5% vs 76.0 +/- 9.7%, mean +/- S.E. p less than 0.05, Student's t-test). After operation, patients in Group A (n = 82) showed a significantly lower %DLco than those in Group B (n = 66) (71.4 +/- 14.3% vs 88.6 +/- 16.8%, p less than 0.05). Preoperative %DLco did not differ between the two groups. Consequently, postoperative decrease in %DLco was characteristic for patients with respiratory symptoms, suggesting that hypoxemia during exercise induced by reduction in diffusion capacity may be responsible for their respiratory symptoms. The anaerobic threshold (AT), and index of aerobic capacity, and symptomlimited maximal oxygen consumption (VO2 max (s.l)), VO2 at the end of exercise, fell to 78.4% and 79.1% of preoperative levels respectively one month after operation. Both indices recovered to 85% of preoperative levels at six months after operation. AT and VO2 max (s.l) values were expressed as a percent of predicted maximal VO2 values for age, body weight and sex (%AT, %VO2 (s.l)). The %VO2 max (s.l) was significantly lower in patients with pneumonectomy (n = 8) as compared with that in patients with lobectomy (n = 55) (51.1 +/- 6.4% vs 60.6 +/- 11.4%, p less than 0.05). Patients with thoracotomy (n = 35) only showed significantly higher %VO2 max (s.l) values (70.5 +/- 12.1%) than those of patients with lobectomy (p less than 0.05). The %AT did not show significant differences among different operative procedure groups. Despite a good preoperative correlation (r = 0.725) between %VO2 max (s.l) and %AT in all patients, there was no correlation between the indices postoperatively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1920975 TI - [Bronchial lavage in the treatment of status asthmaticus]. AB - Bronchial lavage was performed in 10 cases with status asthmaticus who were mechanically ventilated. The mean value of PaCO2 was 64.4 +/- 17.4 Torr before bronchial lavage, and it significantly decreased to 51.9 +/- 11.0 Torr after lavage. In 7 out the 10 cases, bronchial lavage was judged to be effective from the clinical point of view. In 5 cases with values of PaCO2 of over 55 Torr before lavage, massive mucus plugs were recovered. Bronchial lavage was judged to be effective in all of them, whereas three out of the another five cases whose values of PaCO2 were less than 55 Torr showed exacerbation of hypercapnia, and the state of asthma worsened and/or continued for a longer period. The ratio of PaO2/FiO2 did not improve even in effective cases. These results indicated that bronchial lavage is a useful tool to improve the hypercapnic state in patient with status asthmaticus being mechanically ventilated, if the value of PaCO2 is over 55 Torr. PMID- 1920977 TI - [Colony-stimulating factor activity in malignant pleural effusions and its augmentation by local administration of interleukin 2]. AB - The activity of endogenous colony stimulating factor (CSF) in pleural effusions of patients with lung cancer was measured quantitatively by colony-forming bioassay. Before treatment malignant effusions contained various levels of CSF activities. Anti-GM-CSF and anti-M-CSF antibodies neutralized approximately 60% and 70% of CSF activities in malignant effusions, respectively. Significant increase in the CSF activity in malignant effusion was seen during intrapleural injections of recombinant interleukin-2 (IL-2). Thus, in vivo treatment with IL-2 can induce production of endogenous CSF which may be responsible for proliferation and differentiation of mononuclear phagocytes. PMID- 1920978 TI - [Changes in sound transmissibility through the canine thorax due to the experimental pleural effusion]. AB - The authors studied the effects of pleural effusion on sound transmissibility through the canine thorax. In the supine position, dogs received sound ranging from 100 to 1000 Hz at the tracheostoma. Using the microphones attached to the dorsal and ventral part of the chest wall, the relative level of the transmitted sound wave was determined in reference to the amplitude of the sound wave at a tracheostom. Measurements of sound transmissibility were performed before and after injecting saline into the bilateral pleural space which was intended to be experimental pleural effusion. In the dorsal part, the experimental pleural effusion decreased sound transmissibility in the frequency range between 100 and 300 Hz. At 100 Hz, the pleural effusion of 5, 10, and 15 ml/kg/hemithorax caused a decrease in sound transmissibility by 3.7 +/- 3.7, 6.6 +/- 4.9, and 10.0 +/- 5.7 dB, respectively. In the ventral part, the reduction in sound transmissibility in the low frequency range due to the pleural effusion was small. In contrast, introduction of pleural effusion caused an increase in sound transmissibility by 5 to 9 dB in the frequency range above 500 Hz. We consider that these changes in sound transmission are implicated in the physical findings such as "aegophony" and reduction in vocal fremitus or vocal ausculation. PMID- 1920979 TI - [Influence of various factors on glucocorticoid receptors of bronchoalveolar lavage (BAL) cells from rabbits]. AB - It is supposed that the effects of glucocorticoid on target cells are mediated by glucocorticoid receptors. Recent investigations have demonstrated that changes in the composition and function of immune cells in bronchoalveolar lavage (BAL) cells of patients with immunological lung diseases are associated with the intensity of alveolar septal inflammation, or indicate steroid responsiveness. In order to clarify the physiologic changes of glucocorticoid receptor (GR) we measured the GR content of BAL cells obtained from rabbits with various conditions of the host (aging, immunological activation, malnutrition and pretreatment with prednisolone). The specific binding to GR was carried out by incubating BAL cells with 1, 2, 4, 10, 20, 40 nM 3H-prednisolone in the presence or absence of 1.0 x 10(-6) M unlabeled prednisolone. BAL cells from rabbits of various ages exhibited age-dependent reduction of GR content. There were striking differences of GR content in BAL cells from normal and BCG-vaccinated rabbits. The former yielded 3124 +/- 365 binding sites per cell, whereas activated BAL cells showed considerably higher values (6807 +/- 766). Chronological changes in GR content in BAL cells were also observed in normal rabbits pretreated with intravenous injection of prednisolone (2 mg/kg). The GR content was lowest at 3 hours after administration, reaching a peak at two days and then returned to control level. As for nutritional modulation, GR content tended to increase in the initial phase of fasting (days 4 to 8), and then decreased after day 12. In contrast, there were no significant changes in dissociation constants among BAL cells from animals in normal, immunologically activated and malnourished conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920981 TI - [Step section of the TBLB specimens in the diagnosis of sarcoidosis]. AB - The authors analyzed a total of 132 cases clinically diagnosed as sarcoidosis from 1979 to 1990. Routine TBLB sections revealed sarcoid granulomas in 57 cases (Stage 0; 5%, Stage 1; 40%, Stage 2; 57%). In 75 cases in whom routine sections did not show granuloma, we prepared additional sections from paraffin-embedded blocks as step sections. When examined with step sections in addition to routine specimens, the detection rate of sarcoid granuloma increased to 47% in Stage 1 and 82% in Stage 2. We concluded that making step sections of TBLB specimens is a useful diagnostic method in cases suspected of sarcoidosis, especially in Stage 2 cases. PMID- 1920980 TI - [The metabolic index of nocturnal hypoxia in patients after lung resection and thoracoplasty]. AB - The authors measured urinary uric acid (UA) and creatinine (CR), serum lactate, and CoQ10 prior to retiring at night and on awakening in the morning in 127 patients (PG) after lung resection and thoracoplasty which were done more than 20 years age for treatment of tuberculosis and in 20 controls (NC). delta UA:CR, delta lactate, and delta CoQ10 were calculated respectively as the overnight changes in urinary UA:CR and in serum lactate and CoQ10. delta UA:CR increased in PG (4.0 +/- 43.6%), whereas it decreased in NC (-22.3 +/- 17.7%) (mean +/- SD) (p less than 0.05). Nocturnal hypoxemia suggested from positive balance of delta UA:CR was seen in 37% of PG, but in only 10% of NC. delta UA:CR showed no relationship with delta lactate and delta CoQ10 and also did not correlate with the nadir of arterial oxygen saturation. PG were divided into PG with a positive balance of delta UA:CR (PG-P) and with a negative balance of delta UA:CR (PG-N). The %VC and PaO2 in the PG-P group were lower and PaCO2 was higher than in PG-N, although the difference did not achieve statistical significance. PMID- 1920982 TI - [Downhill esophageal varices due to superior vena cava syndrome]. AB - This study examined the incidence of downhill esophageal varices due to SVC syndrome. The presence of downhill esophageal varices was examined by esophagoscopy or autopsy. Downhill esophageal varices were detected in two of nine (22%) patients with SVC syndrome. One case was a 66-year-old male case who and underwent upper lobectomy for lung cancer in September 1985. He developed SVC syndrome due to recurrence in 1986 and died in 1987. Downhill esophageal varices wer in the upper esophagus by esophagoscopy and confirmed by autopsy. The another case was a 61-year-old female who developed carcinoma of the tongue in 1986 and lymph node metastasis to the mediastinum in 1987. Autopsy revealed downhill esophageal varices in the upper and middle esophagus. Eleven cases of downhill esophageal varices due to SVC syndrome reported in Japan were reviewed and discussed. PMID- 1920983 TI - [The CT diagnosis of emphysema and correlation with pathologic findings]. AB - It is difficult to diagnose clinically silent or mild emphysema. The efficacy of CT scans for the diagnosis of emphysema has attracted attention and comparisons have been made between CT images and the pathological grade of emphysema in resected lungs. With a view to determine to what extent high resolution CT images are accurate concerning the diagnosis of mild emphysema, we conducted an extensive comparative study on CT scores of emphysema, based on high resolution CT, the pathology score derived from the cut surface of the lung identical in its plane with that of the CT and destructive index (DI) which is said to be instrumental in representing the degree of deterioration of alveolar walls in the same regions of the lungs. In this study, 42 patients who underwent thoracotomy and their lung specimens including a solitary nodule of considerable size have been employed. The CT scores and pathology scores depend on the picture grading system developed by Thurlbeck and coworkers for the basis of counting. The findings were such that with 1 mm collimation, the CT scores ranged between 12 and 57 with a mean +/- SD of 22.1 +/- 9.6 (n = 35) while with 5 mm collimation, the CT scores ranged between 7 and 46 with a mean +/- SD of 16.5 +/- 8.3 (n = 33). The pathology scores stood at 10 to 57 with a mean +/- SD of 23.2 +/- 9.8 (n = 42).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1920984 TI - [A clinical study on intrathoracic malignant lymphoma with chronic tuberculous pyothorax]. AB - The authors reported 3 male patients of malignant lymphoma developing from long standing pyothorax. They had been suffering from tuberculous pyothorax for more than 30 years, after artificial pneumothorax therapy for pulmonary tuberculosis. The most common symptom was chest pain. It was difficult to detect the tumor mass by chest X-ray because of old inflammatory changes. Computed tomography and 67Ga scintigraphy were useful. The lesions tended to grow destroying the surrounding lung, chest wall and ribs. Histologically, 2 cases were diffuse large cell type and one was diffuse intermediate sized cell type. Immunologically, 2 cases were B cell type lymphoma but one was not clearly classified. They received radiotherapy, but 2 cases died of respiratory failure. These findings suggest that B cell lymphoma might arise following chronic tuberculous pyothorax. Therefore such cases should be followed up carefully. PMID- 1920985 TI - [A case of congenital bronchial atresia with obstructive pneumonia accompanied with partial anomalous pulmonary venous drainage]. AB - A 25-year-old male was admitted with productive cough and an abnormal shadow on chest X-ray film which showed a cylindrical shadow near the left hilum and consolidation in the markedly hyperlucent left upper lung field. The cylindrical shadow appeared to be located in left S1+2 but bronchographic examination showed independence of the branches of B1+2. Furthermore, pulmonary venography by DSA showed that the left upper pulmonary vein entered the left brachiocephalic vein. The patient underwent left partial lobectomy under a diagnosis of congenital bronchial atresia with partial anomalous pulmonary venous drainage. Pathological examination of the resected lung revealed obstructive pneumonia in the over inflated lung zone, probably induced through collateral airways. PMID- 1920986 TI - [A case of Pneumocystis carinii pneumonia with bronchial asthma following long term corticosteroid therapy]. AB - A 50-year-old man, who developed bronchial asthma at the age of 43 and was treated continuously with corticosteroids from the beginning of the first treatment, was admitted with exacerbation of exertional dyspnea. In spite of various treatments for bronchial asthma, such as theophylline, beta-stimulants, anti-allergic drugs and steroid-inhalation, asthmatic symptoms did not improve and he continued to receive intravenous administration of steroids. Five months after admission, he suddenly developed severe respiratory failure and died after five days. Autopsy revealed Pneumocystis carinii pneumonia and marked atrophy of adrenal glands. No evidence of malignancy or hematologic disease was seen. Serum HIV antibody was negative. Secondary immunodeficiency induced by long-term corticosteroid administration of over 7 years was considered to be the cause of Pneumocystis carinii pneumonia. It seems that no case of Pneumocystis carinii pneumonia with bronchial asthma alone has ever been reported in medical literature. PMID- 1920987 TI - [A case of oral gold tablet-induced interstitial pneumonitis]. AB - A 76-year-old woman was admitted with exertional dyspnea and chest roentgenographical abnormal shadows appearing after oral gold therapy (total 720 mg) for rheumatoid arthritis. Based on the patient's clinical course, chest roentgenograms, chest CT and pathological findings of TBLB specimens, gold pneumonitis was diagnosed. Steroid therapy improved symptoms and pulmonary function and cotton-like shadows on chest roentgenograms and chest CT scanning. However, linear and large ringed shadows on chest roentgenograms and chest CT scan remained, even after steroid therapy. This case is the first case of oral gold tablet-induced pneumonitis. Although the mechanism of oral gold tablet induced pneumonitis is considered to be almost the same that of gold injection therapy-induced pneumonitis, this case suggested that fibrotic changes in oral gold tablet-induced pneumonitis may be delayed over a long period. PMID- 1920988 TI - [A case of diffuse panbronchiolitis, performed an open lung biopsy after improvement with 6 years medication]. AB - A 51-year-old male was hospitalized in June 1983, complaining of productive cough and dyspnea. Diffuse panbronchiolitis (DPB) was diagnosed on the basis of the physical examination, chest roentgenogram, chest CT and transbronchial lung biopsy (TBLB). The patient underwent surgery for chronic sinusitis and deviated nasal septum, and received Pseudomonas aeruginosa vaccine, ampicillin and erythromycin. He revealed a posterior mediastinal tumor in March 1989. The clinical findings of DPB improved but open lung biopsy was performed on the occasion of surgery for the posterior mediastinal tumor. Pathologically, fibrosis and mild infiltration of mononuclear cells localized in the walls of respiratory bronchioli and in surrounding areas was recognized in addition to slight accumulation of foamy macrophages in interstitial spaces. These morphological findings, as well as the clinical findings, might suggest repair of DPB lesions. PMID- 1920989 TI - [Two cases of primary lung cancer with initial symptoms due to ocular metastases]. AB - Two cases of primary lung cancer with initial symptoms due to metastasis to the eye or the orbit are reported. Case 1 had orbital metastasis, while case 2 had intraocular metastasis. It has been reported that the survival period is short after the metastasis was found. In our cases, the survived periods for case 1 and case 2 were 3.5 months and one month, respectively. PMID- 1920990 TI - [A case of pulmonary aspergillosis presenting pulmonary bulla and eosinophilic pneumonia]. AB - A rare case of a 25-year-old man with pulmonary aspergillosis is reported. Pulmonary bulla and eosinophilic pneumonia in the right upper lobe were diagnosed by chest roentgenogram and transbronchial lung biopsy. Because the patient developed infective bullae during steroid therapy, we performed transcutaneous thoracic drainage and right upper lobectomy. The resected lung tissue contained numerous hyphae of Aspergillus. Around the hyphae of Aspergillus, granulomatous reaction and eosinophilic infiltration were observed. Antibodies against Aspergillus were detected in the serum of the patient. The number of peripheral blood eosinophils decreased after right upper lobectomy. These findings suggest that pulmonary bullae and eosinophilic pneumonia may be a rare manifestation of pulmonary aspergillosis. PMID- 1920991 TI - [Squamous cell carcinoma of the thymus]. AB - A 68-year-old woman was admitted with cough and dyspnea. Her chest X-ray showed right pleural effusion and a mediastinal tumor. She underwent mediastinotomy following a preoperative diagnosis of invasive thymoma. A tumor originating from the thymus had invaded the right middle lobe and pericardium, and multiple pleural dissemination was also found. Therefore, considering the patient's age and pulmonary function, we performed only subtotal resection of the tumor. The pathological diagnosis was poorly differentiated squamous cell carcinoma. The patient received irradiation and chemotherapy including Cisplatin after surgery, but she died 1 year later because of rapid progression of distant metastases. PMID- 1920992 TI - [A case of pulmonary aspergillosis with a tumor shadow, diagnosed by transbronchial aspiration cytology]. AB - A 41-year-old female was admitted because of cough and hemosputum. She had no underlying disease and the presence of respiratory disease had not been pointed out. Chest X-ray and CT scan showed a solid, homogeneous tumor with a distinct margin near the right hilum. The tumor measured approximately 5 x 4 cm. Because other laboratory data concerning the serum levels of tumor marker and anti aspergillus antibody were normal, benign lung tumor or malignant lymphoma was suspected at first. Transbronchial cytology and biopsy were performed, but there were no significant findings. However transbronchial aspiration cytology of the specimen obtained from the bifurcation between the right upper lobe bronchus and the truncus intermedius demonstrated Aspergillus. After the administration of antifungal drugs, the tumor decreased in size, and an air crescent sign appeared. This was thought to be a very rare case of locally invasive form of pulmonary aspergillosis, as described by Sider et al demonstrating a necrotic fungal ball during its clinical course. PMID- 1920993 TI - [A case of squamous cell carcinoma of the thymus and thymic cyst]. AB - A 57-year-old man was referred to our hospital for further evaluation of an abnormal mediastinal shadow detected on chest X-ray film. Chest CT showed a solid mass and a cyst. Operation revealed a squamous cell carcinoma of the thymus adjacent to a thymic cyst. Histologic examination demonstrated the clear separation of the squamous cell carcinoma and the thymic cyst by interstitial tissue. Cases of squamous cell carcinoma of the thymus combined with thymic cyst are very rare. PMID- 1920994 TI - [A case of left intrathoracic kidney with renal anomalies]. AB - A rare case of intrathoracic kidney was reported. A 71-year-old female with no complaint presented for evaluation of an abnormal shadow in the left lung field. A routine chest roentgenograms showed a sharply outlined mass in the postero medial portion of the left lung field. Computed tomography demonstrated left intrathoracic kidney with anomalies of rotation. Intravenous pyelography demonstrated a left high ectopic kidney with complete duplication of the renal pelvis and incomplete duplication of a ureter. The patient was diagnosed as left intrathoracic kidney with renal anomalies. The 79 cases of intrathoracic kidney reported in Japan were analyzed concerning their etiology. PMID- 1920995 TI - [Metastases to the mediastinal lymph nodes in a series of two-hundred-consecutive operations for primary lung cancer]. AB - We examined the characteristics of lymph nodes metastases to the mediastinum on cases of two-hundred-consecutive operations for primary lung cancer from October of 1987 to May of 1990, comparing the intraoperative macroscopic diagnosis of lymph nodes to the histologic reports. The purpose of this study is to know how important the mediastinal dissection is and how many cases resulting in vain are hidden behind it. Thirty three cases were excluded because of limited operation or other reasons. Remaining a hundred sixty seven cases were divided on the basis of lymph node metastasis into following 5 groups. Forty three cases (26%), of which N2 disease was correctly diagnosed macroscopically, true positive for N2, were classified into group A. Sixteen cases (10%), group B, in which we failed to detect N2 positive from dissected specimens during operation, was considered to be false negative for N2, thirty one cases of N1 disease (18%), were classified into group C and thirteen cases of N0 disease (8%) into group D with false positive of lymph node prediction for metastasis. Sixty four cases of N0 disease (40%) were classified into group E, true negative for N0 prediction, which were correctly detected by macroscopic appearance of lymph nodes. Nine cases had only mediastinal lymph nodes metastases without hilar and lobar lymph node. Almost of them with this skip phenomenon occurred in the patients with adenocarcinoma in the upper lobe. It could be concluded that we dissected the mediastinal lymph nodes in this series, salvaging one N2 disease of ten cases and wasting our efforts four cases of those cases, in vain. PMID- 1920996 TI - [Emergent coronary artery bypass grafting (CABG) for over-80-year-old patients]. AB - We experienced 2 emergent CABG for over-80-year-old patients. First patient, an 81-year-old male, showed total occlusion of left main truncus (LMT) and 90% stenosis of right coronary artery (RCA), and fell in shock. He underwent PTCA for LMT under intraaortic balloon pumping (IABP) and recovered from shock. But 3 days later, pulmonary congestion and heart failure developed along with mitral regurgitation. Emergent CABG to left anterior descending branch (LAD) and RCA was performed using saphenous vein grafts in combination with mitral annuloplasty by Kay's method. Second patient, an 82-year-old male, showed 50% stenosis of LMT, 99% stenosis of LAD and total occlusion of RCA, and fell in shock. Emergent CABG to LAD and RCA was performed using saphenous vein grafts under IABP. In spite of some perioperative serious complications, both patients survived and have been doing well. Some problems of CABG for elderly patients were discussed. PMID- 1920997 TI - [Long-term results of porcine bioprosthetic valves]. AB - Between November 1977 and October 1980, 54 patients underwent valve replacements with porcine bioprostheses at Hyogo Kenritsu Amagasaki Hospital. The late complications and the long term durability of 53 porcine bioprostheses were documented in 48 patients after discharge (34 mitral, 7 aortic, 2 tricuspid, and 5 multiple, consisting of 38 Hancock, 15 Carpentier-Edwards prostheses). Cumulative duration of follow-up is 420 patient-years. The valve related late mortality was 0.52%/patient-years. There were 6 thromboembolic events (1.6% patient-years), only 1 episode of endocarditis (0.26%/patient-years). Valve dysfunction is defined as stenosis or regurgitation by echocardiogram or cardiac catheterization. There were 21 instances of porcine bioprosthetic dysfunction (6.6% patient-years). Freedom from valve dysfunction at 12 years was 24.4%. There were 17 valves of mitral bioprosthetic dysfunction (6.4% patient-years). The incidences of mitral stenosis (MS), mitral regurgitation (MR), and paravalvular leakage were 4.5, 3.6, and 0.7%/patient-years respectively. Freedom from MR was higher than MS at 8 years. The 14 patients were needed reoperation due to valve dysfunction (3.6%/patient-years). We concluded that the porcine bioprostheses showed a high incidence of valve dysfunction at 7 to 8 years after operation, we presently choose mechanical valve in most cases. PMID- 1920998 TI - [Assessment of coronary bypass surgery by continuous ventricular function monitoring]. AB - The sequential change of left ventricular function during exercise and recovery after exercise was assessed in 50 patients who had undergone coronary bypass surgery before and after the operation by means of continuous ventricular function monitoring system (VEST). Cardiac response was divided into 4 types with respect to the profiles of the left ventricular ejection fraction during exercise. Type A continued to increase; type B initially increased but decreased in severe exercise stages; type C did not change during exercise; type D continued to decrease. Most patients showed type C or D before surgery but showed type A after surgery. 9 patients with occluded grafts or ungrafted coronary arteries showed type B, C or D. Two patients with extended infarction and poor left ventricular function showed type C after surgery. In recovery period after exercise, the ejection fraction showed an overshoot. The mean ratio of peak ejection fraction during recovery to ejection fraction at rest increased from +62 +/- 12% before operation to +68 +/- 16% after operation (p less than 0.05). The recovery time after exercise was decreased from 195 sec before operation to 98 sec after operation (p less than 0.01). VEST revealed response of left ventricular function during exercise and recovery after exercise as far as detail abnormalities. PMID- 1920999 TI - [A case of graft-versus-host disease following irradiated fresh blood transfusion]. AB - We reported a case of a fatal graft-versus-host disease (GVHD) which developed in a 65-year-old, male patient which was considered to have been induced by irradiated fresh blood donated by his son after a coronary bypass surgery. Fresh blood was obtained from his relatives, and a 15 Gy irradiation was performed before transfusion. The diagnosis of acute GVHD was made by clinical symptoms and histological examinations of the skin and the bone marrow. He died of sepsis on the 19th post-operative day. The HLA typing of the lymphocytes, revealed that the patient had A 2, A 24, Bw 52, Bw 62, Cw 4, DR 2, and his son had A 24, Bw 52, DR 2. A 24 and Bw 52 were homogeneous making his son histocompatible with one of the patient's haplotype. This might well be attributable to the occurrence of GVHD in this case, meaning that 15 Gy irradiation was not sufficient for the prevention of this disease. PMID- 1921000 TI - [Selection and management of donor hearts in infant and pediatric heart transplantation: Loma Linda experience]. AB - One hundred and six infant and pediatric patients received 108 heart transplantations between November 1985 and December 1990. The age of the recipients was from 0 day to 12 years (mean 11.1 months) and the age of the donors were from 2 days to 24 years (mean 18.3 months). The body weight ratio of donor and recipient were from 59% to 315% (mean 163%). Large donor hearts were well tolerated without serious complication even in small infants. The graft ischemic time was from 51 minutes to 505 minutes (mean 244 minutes) and fifty four grafts had ischemic time more than 4 hours. There was no difference of the frequency of primary graft failure between the grafts with longer and shorter ischemic time. Although diastolic function in the first week post-transplant was more depressed in the grafts with longer ischemic time, no difference was observed after the second post-transplant week. There was no difference in the systolic function in accordance with the ischemic time. Eight hours and more ischemic time was well tolerated in our donor grafts. PMID- 1921001 TI - [The perioperative management of dialysis for patients undergoing coronary artery bypass surgery with chronic renal failure]. AB - Several methods of dialysis have been employed to maintain the perioperative water-electrolyte balance caused by the disorders with chronic renal failure. We have experienced 13 cases of coronary artery bypass surgery with chronic renal failure, and employed hemodialysis (HD) in 5 cases, hemodialysis with extracorporeal ultrafiltration method (HD + ECUM) in 5 cases, continuous ambulatory peritoneal dialysis (CAPD) in 3 cases for perioperative management. The perioperative changes of the circulatory blood volume and the fluid-balance, were assumed by positive reaction with varied over 60 mmHg in systolic blood pressure or demanded over double dose of catecholamines in each observed terms until the next day of the patients extubated. The cases with HD or HD + ECUM have changed the blood pressure more frequently (HD cases = 21%, HD + ECUM cases = 19%) than the cases with CAPD (CAPD cases = 3%). We conclude that the each methods are available to manage perioperative dialysis to undergo coronary artery bypass grafting should be employed with some techniques, CAPD will be the most favorable method to maintain the fluid balance stably for patients with severe compromised cardiac function. PMID- 1921002 TI - [Clinical experience of intramediastinal injection therapy via mediastinoscope for lung cancer]. AB - As local treatments other than surgery, radiation therapy, bronchial artery infusion and intrabronchial injection of anti-cancer drugs have generally been administered to inoperative lung cancer cases. Together with these local therapies, we experienced six cases of intramediastinal injection. Indication of this therapy has been fundamentally limited to the inoperative cases in which patient performance status has deteriorated. Histologically, three cases were squamous cell carcinoma and three cases were adenocarcinoma. Injection therapy was effective in four cases where we noted alleviation of atelectasis and obstructive pneumonia brought on by the tumor, and a tendency of the tumor and swelling lymph nodes to be reduced. No side effects nor complications were evidenced. This therapy is characterized by a wider injection area in which intrabronchial injection is incapable of reaching the upper mediastinum, the bifurcation and the upper side of the hilus. The results suggest that this therapy should be used alone or together with other local therapies and prior to operation. PMID- 1921003 TI - [Role of combined pulmonary resection during descending thoracic aortic aneurysmectomy]. AB - Between April, 1982 and December 1990, five of 98 patients who underwent aneurysm repair for the thoracic aorta received combined resection of the descending thoracic aortic aneurysm and the lung because of marked adhesion between the aneurysm and the lung. Partial resection of the upper lobe of the lung was performed in all of five patients with auto-suture device. Three of the five patients needed no homologous blood transfusion during the surgery. Neither operative death nor pulmonary complication related to lung injury and bleeding was noticed. Our results indicate that partial resection of the lung is beneficial for avoiding intra-operative rupture of the aneurysm as well as lung injury in patients with descending thoracic aortic aneurysm severely adherent to the lung. PMID- 1921004 TI - [A case report of total removal of infected pacemaker with cardiopulmonary bypass]. AB - A successful removal of infected pacemaker with septicemia, pre-DIC state, and pneumonia is reported. A 44-year-old man received transvenous permanent pacemaker implantation through right subclavian region at 42 years of age. Two years and 3 months after implantation an abscess formed around the generator. Since incision and drainage were not effective, the generator was removed after 2 months (another pacemaker was reimplanted at the opposite side), and the initial pacing lead was cut after 3 months of initiation of the infection. But wound healing was not obtained and high fever-up occurred. Arterial blood culture showed septicemia caused by Staphylococcus aureus. He also suffered pre-DIC state and pneumonia. The end of the cut lead had fallen into the right ventricle. After general condition was recovered, the residual lead and the reimplanted pacemaker system were extirpated under cardiopulmonary bypass. And at the same time a new pacemaker system was implanted again. He was in good postoperative course, and he is up and well 8 months after operation. PMID- 1921005 TI - [A case of benign pulmonary metastasis from ovarian immature teratoma]. AB - A thirty one-year-old female underwent resection for pulmonary metastatic tumor from immature ovarian teratoma (G-II). Resected specimens from the lung revealed no malignant findings in the cystic teratoma (G-0). We speculated this finding might be due to retroconversion of ovarian immature teratoma. Retroconversion of ovarian immature teratoma is rarely reported and no report was found which dealt with pulmonary metastatic lesion histologically. PMID- 1921006 TI - [A simultaneous operation of CABG and bilateral femoropopliteal bypass: report of a successful case]. AB - A 62-year-old man with both coronary artery disease and leg ischemia was successfully treated with a combined revascularization procedure. Coronary artery bypass grafting (CABG) was carried out using in situ left internal thoracic artery and right gastroepiploic artery grafts, and bilateral femoropopliteal bypass grafting were performed reversed saphenous vein grafts simultaneously. The patient recovered well and experienced neither angina nor intermittent claudication. PMID- 1921007 TI - [Closed stuck valve diagnosed by echocardiogram immediately after mitral valve replacement: a case report]. AB - The patient was a 52-year-old woman who suffered from mitral valve regurgitation due to torn chordae. Mitral valve replacement (Medtronic-Hall 27 mm) was performed on Jan. 30, 1990. Immediately after the operation cardiac pacing was necessary for bradycardia, but one hour later cardiac rhythm changed to atrial fibrillation and the patient received an injection of verapamil. After the treatment of tachycardia, electro-mechanical dissociation (EMD) appeared on monitor. Bed side M-mode echocardiogram disclosed a restriction of the disc opening, but abnormal structures were not detected by B-mode echocardiogram. By repeated echocardiogram, the disc opening was normally demonstrated on M-mode, but B-mode showed an abnormally high echo structure in the left ventricle just below the prosthetic valve. Under the diagnosis of stuck valve in the closed position due to remnants of chordae, reoperation was performed. An eight mm remnant of chorda was found on the posteromedial side of the posterior leaflet, and it was supposed that the compression of the remnant between the disc and the valve ring restricted the valve opening. The remnant was resected through the large orifice of the Medtronic-Hall valve. After the reoperation, EMD was not detected and prosthetic valve insufficiency was not noted on echocardiogram. The patient left the hospital in a good condition three weeks after MVR. PMID- 1921008 TI - [A case of Klinefelter's syndrome with acute mitral regurgitation caused by idiopathic chordal rupture]. AB - It has been reported that the incidence of mitral valve prolapse was remarkably increased in patients with Klinefelter's syndrome. Some cases which have been previously reported were associated with hemodynamically significant transvalvular regurgitation, however, none of them underwent a surgical treatment such as valvular replacement. Here we report a case of Klinefelter's syndrome which underwent MVR for mitral regurgitation caused by idiopathic chordal rupture. Pathological microscopic examination showed topical and minor myxomatous changes on the free edge of the leaflet and no inflammatory changes such as in infectious endocarditis. It is, therefore, suggested that an echocardiographic follow-up should be carried out in case of Klinefelter's syndrome during its life and also in the case treated by a prophylactic therapy for endocarditis with antibiotics. And when, unfortunately, surgical treatment is required, valve replacement would be preferable to valvuloplasty because of a fragility of leaflet. PMID- 1921009 TI - [Congenital kinking of the aortic arch associated with aortic arch aneurysm: a case report]. AB - A surgical case of congenital kinking of the aortic arch associated with aortic arch aneurysm, which had been observed as the mediastinal tumor for 15 years, was reported. Twenty-two surgical cases of the aortic lesion, which were diagnosed pseudocoarctation or congenital kinking, have been reported in the literature. This paper focused on the pathogenesis, surgical treatment and terminology of this anomaly. PMID- 1921010 TI - [A case of intrathoracic multiple schwannoma]. AB - A case of intrathoracic multiple schwannoma originating in the left sympathetic nerve was reported. A 38-year-old male was admitted to our department for re evaluation of his nephrotic syndrome, the chest X-ray revealed an abnormal shadow. A chest tomogram and a chest computed tomogram revealed multiple masses along the left 10th thoracic vertebra. The operation was done on September 4, 1989 under the diagnosis of posterior mediastinal tumor. At thoracotomy, four tumors were seen along the 10th thoracic vertebra and the sympathetic nerve was ascertained to be connected. Histologically, the tumors were composed of spindle cells arranged in scattered palisading fashion, and diagnosed as schwannoma. Multiple schwannomas are very rare. There have been only 12 cases of intrathoracic multiple schwannoma in Japan. Available Japanese literature on the subject was reviewed and discussed. PMID- 1921011 TI - [A case report of aortic stenosis complicated with complete atrioventricular block]. AB - A case of aortic stenosis complicated with complete atrioventricular block preoperatively was reported. The patient was a 73-year-old woman who had been suffering from dyspnea and fatigability. Preoperative echocardiography revealed severe left ventricular hypertrophy, marked left ventricular-aortic pressure gradient (144 mmHg), and the impairment of left ventricular distensibility. Therefore, DDD pacemaker was implanted in addition to aortic valve replacement. Postoperative cardiac catheterization revealed that cardiac output was increased about 25% by DDD pacing compared with VVI pacing. It is more reasonable to employ DDD pacemaker to the case of which distensibility is impaired. PMID- 1921012 TI - [Can TURP play a leading role in the end of the century?]. PMID- 1921013 TI - [A study of BBN induced bladder cancer in mice. The time differences in changes of histopathology and nuclear DNA content]. AB - To evaluate the process of tumor progression in BBN induced bladder cancer, BBN was administered to C57BL/6 mice for 10 weeks. The mice were sacrificed every week from the 5th week to the 22nd week. The urinary bladder was embedded in paraffin block for histopathological examination and was sampled for DNA content analysis by flow cytometry. The results were as follows: 1. In the histopathological findings, the incidence of atypical hyperplasia of the urinary bladder, indicative of a precancerous state, was 29% 7 weeks after the initiation with BBN. And the cancer was found in 74% of the mice 9 weeks after the initiation. 2. In the analysis of nuclear DNA content, the atypical hyperplasia and the incipient cancer of the urinary bladder were all DNA diploid, and the DNA aneuploid was found in 50% of the cancer group 11 weeks after the initiation. 3. These data suggest that the change of nuclear DNA content is an occurrence after the completion of the carcinogenesis in BBN induced bladder cancer of mice. PMID- 1921014 TI - [Effects of recombinant interleukin 1 beta on peripheral blood cells and induction of lymphokine-activated killer activity in patients with urological malignancies]. AB - Subcutaneous injection of human recombinant interleukin 1 (IL-1) beta was given to 9 patients with urological malignancies (5 renal cell carcinoma, 2 bladder carcinoma, 1 renal pelvic tumor, and 1 testicular tumor), at an initial dose of 1 x 10(4) units on days 1 and 2, and there after weekly for 4 weeks. The dose was increased by 1 x 10(4) units weekly up to final dose of 4 x 10(4) units. Peripheral blood mononuclear cells (PBMC) were isolated from patients on day 3 in week 2 and week 4, and lymphokine-activated killer (LAK) activity against Daudi cells was measured using 4 hr 51Cr-release assay, after incubation with human recombinant interleukin 2 (IL-2) of 50 units/ml for 72 hours. Proliferation of lymphocytes was measured by tritiated thymidine incorporation after incubation with IL-2 for 72 hours. IL-1 beta increased the number of peripheral blood granulocytes and lymphocytes, but did not increase the numbers of monocytes and platelets. IL-1 beta significantly augmented IL-2-induced LAK activity in vitro, but this augmentation was neither accompanied by the increase of IL-2 receptor positive cell ratio in peripheral blood lymphocytes nor enhancement of IL-2 induced proliferation of lymphocytes. Administration of IL-1 beta increased LAK activity of the patients, despite the fact that IL-1 beta did not increase LAK activity in vitro. The result suggests that IL-1 beta-stimulated LAK activity may be mediated by the induction of some cytokines in the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921015 TI - [Early experience with an ileocolic bladder substitution (Mainz pouch) in 11 cases]. AB - In the last decade, many continent urinary diversions have been developed for the cystectomy patients. Mainz pouch, which seems to be a sophisticated one without using an alloplastic prosthesis, was adopted in our clinic. We preliminarily report our result in 11 patients who underwent a Mainz pouch procedure in the last 2 years: 1 for bladder augmentation, 5 for total bladder substitution after cystoprostatectomy and 5 (including 2 females) for continent urinary diversion. The mean age of them was 54 years old and the follow up periods ranged from 6 to 24 months. The antimesenteric longitudinal incision of the ileum and cecum and their sutures were performed similarly to the usual detubularized intestinal pouch. The ureteral reimplantation to the colonic segment was accomplished by the submucosal tunnel method. Although the ureteral hiatus was initially positioned at the anal edge of the colon, a new hiatal creation by stabbing the more oral portion of the colon according to the Goodwin's ureterocolic anastomosis was subsequently employed to avoid the trouble of closure of this portion. When the urethral anastomosis was achieved by 4-5 interrupted sutures between the most dependent portion of the cecum and the urethral stump after cystoprostatectomy, the mucosa was everted to the colonic serosa to prevent the stricture. The continent stoma was created by an intussusception of the proximal ileum, which was stabilized by the seromuscular stripping and 2-3 rows of external metal staples. Complication of the alimentary system occurred in 6 of 11 cases (55%), though they were successfully treated by an appropriate conservative management except one who suffered an ileostomy and nephrostomy because of severe panperitonitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921016 TI - [The progress pattern of carcinoma in situ of the urinary bladder]. AB - Forty patients with carcinoma in situ of the bladder were reviewed. They included 15 patients with primary carcinoma in situ, 8 with secondary carcinoma in situ and 17 with concurrent carcinoma in situ. Twenty-one (66%) of 32 patients with primary or concurrent carcinoma in situ complained of urinary frequency and pain on urination, whereas no patients with secondary carcinoma in situ complained of such symptoms. Nearly all patients with concurrent or secondary carcinoma in situ had gross hematuria, whereas only 7 (47%) of 15 patients with primary carcinoma in situ had gross hematuria. Two patients without any symptoms were diagnosed by incidental positive urinary cytology. Concurrent carcinoma in situ was always associated with multiple papillary tumor. Dominant grade of the papillary tumor was classified as grade 3 in 11 patients and as grade 2 in 6. The simultaneous presence of carcinoma in situ of the urethra was found in 13 (46%) patients and those of the ureter in 17 (74%). Fourteen patients (35%) with carcinoma in situ developed an invasive carcinoma. Of these, 4 (10%) died of cancer. Bacillus calmette-guerin instillation was effective in 13 of 15 patients (87%). These results indicate that carcinoma in situ of the bladder may develop an invasive cancer, may remain in the epithelia, or may be associated with multiple superficial tumor. It should be emphasized that patients with multiple superficial bladder tumor may be associated with carcinoma in situ even if the superficial tumors are of low grade and urine cytology is negative. PMID- 1921017 TI - [Treatment of seventy-eight patients with testicular tumors]. AB - Seventy-eight patients with testicular tumors were treated in our clinic between April, 1972 and October, 1990. The average age of patients with seminoma (37.5 yrs) was higher than that (24.5 yrs) of those with non-seminomatous germ cell tumor (NSGCT). Histopathologically, 34 patients had seminoma and 36 patients had NSGCT. The remaining 8 patients had non-germinal cell tumors. The 5-year survival rate was 76.7%, 90.3% and 75.8% for all patients, seminoma group and NSGCT group, respectively. As for seminoma group, the 5-year survival rate was 100%, 50.0% and 33.3% for Stage I, Stage IIb and Stage III, respectively. The survival rate of Stage IIb and Stage III in seminoma group were lower than Stage I statistically. In NSGCT group, the 5-year survival rate was 100% for Stage I and 26.7% for Stage III, between the two groups there was significant difference. The higher serum LDH and HCG levels, the lower the survival rate in NSGCT. Serum AFP, beta-HCG levels and ESR were unrelated to the survival rate. The survival rate for the patients treated by the chemotherapy including CDDP was compared to those treated by the other therapy in germ cell tumor (greater than or equal to Stage IIb). The survival rate of CDDP group was higher than the others (p less than 0.01). PMID- 1921018 TI - [S100a0 protein and creatine kinase isozymes (CK-B & CK-M) in serum and urine might be useful markers for non specific tissue damages by extracorporeal shockwave lithotripsy (ESWL)]. AB - In order to demonstrate that the extracorporeal shockwave lithotripsy (ESWL) for urolithiasis causes a renal damage, we immunoassayed S100a0 protein and creatine kinase isozymes (CK-B & CK-M) in the serum and urine from patients with renal stone (N = 21) and those with ureteral stone (N = 18) before and after ESWL. S100a0 protein and CK-B, which are localized in the proximal renal tubules at relatively high concentrations, were enhanced more or less both in the urine and serum samples after the treatment in both groups of patients. Since CK-M, which is mainly localized in muscle tissue, also increased in both groups of patients, S100a0 protein and CK-B may be derived not only from kidney, but also from muscle tissues. PMID- 1921020 TI - [Urinary cytology in patients with urolithiasis]. AB - Urinary cytological examination was performed on 1032 patients of urolithiasis at the Department of Urology, Chiba University Hospital between 1980 and 1990. Seven hundred twenty-four were male and 308 were female, and the mean age was 44 years. The results of cytological examination of I-II and IV-V were classified as negative and positive, respectively. Eleven patients (1.1%) were positive, 2 of whom were found to be with renal pelvic tumor. False-positive findings were noticed in 9 cases (0.9%), and the abnormal cytologic changes in these cases disappeared after the calculi were removed. In negative cytological cases, 2 cases of renal pelvic tumor were found, one at nephrectomy and the other at percutaneous nephrolithotripsy. These cases were with staghorn calculi with hydronephrosis. The significance of cytological examination in management of calculous diseases were discussed. PMID- 1921021 TI - [Cyclosporine induced nephrotoxicity and juxtaglomerular apparatus in mice]. AB - To elucidate the relationship between Cyclosporine (Cs) induced nephrotoxicity and juxtaglomerular (JG) apparatus, we carried out biochemical and morphological experiments using mice. Adult male ICR strain mice weighing about 40 g were used. The mice were divided into 2 groups: the Cs group (Cs 50 mg/kg/day was orally given for 14 consecutive days) and the control group (olive oil for 14 days). Urine was stored for 24 hours on the day 0, 7 and 14 and urine volume and concentrations of urinary creatinine (u-Cr) and urinary potassium (u-K) were measured in each group. All the mice were sacrificed and examined on the 15th day. Concentrations of serum creatinine (s-Cr), serum potassium (s-K), plasma renin activity (PRA), plasma aldosterone (Ald) were noted in each group. The kidneys were also examined histologically with light and electron microscopes. The Cs group showed significant increases of s-K, PRA and Ald and a significant decrease of creatinine clearance compared with the control group. Histologically, the Cs group demonstrated focal vacuolar changes in the proximal tubular cells and an increase in the number of granules in the JG cells. Each granule of the Cs group was larger than that of the control group. Cs certainly stimulates the renin-angiotensin-aldosterone system and causes consequently a secondary aldosteronism. PMID- 1921022 TI - [Clinical analysis of urinary incontinence in the institutionalized elderly]. AB - Urinary incontinence among institutionalized elderly were analyzed from clinical and social viewpoints. The patient group included 25 males and 107 females with an average age of 78 years (ranged from 66 to 92). They had neither highly impaired performance status nor severe dementia. Forty-nine of them (37%) underwent urological examination. Urge incontinence was common among male patients, while urge, stress or mixed incontinence were prevalent in female patients. Thirty-six per cent of the patients had to use pads, diapers and others for their incontinence, while other needed no special protection for their incontinence. Incontinence caused limitation of social activity in 30% of the patients. Many causal factors were assumed for incontinence in elderly; weakness of the pelvic muscles, urinary tract infection, cerebrovascular disorders, neurological disorders and prior pelvic surgery. Prostatic carcinoma or urethral stricture caused overflow incontinence in a few patients. Diuretics or tranquilizers appeared to lead incontinence in some patients. Nine of 18 patients undergoing cystometry had overactive detrusor. Majority of the incontinent elderly showed no intention to visit clinics. Therefore, it recommended to keep staffs in elderly institutions as well as elderly themselves informed that incontinence in the elderly should be treated, which in turn improves the quality of life. PMID- 1921019 TI - [Investigation of postoperative adjuvant chemotherapy in patients with transitional cell carcinoma of the upper urothelium. Nara Urooncology Research Group (NUORG)]. AB - During the 5 years from January, 1985 to December, 1989, 88 patients with transitional cell carcinoma of the renal pelvis and/or ureter were operated curatively in the Department of Urology, Nara Medical University and the affiliated hospitals. There were 66 males and 22 females (3:1) and the mean age was 66.0 years old ranging from 34 to 82. Staging of the renal pelvic and ureteral cancer of each patient was determined by General Rule for Clinical and Pathological Studies on Renal Pelvic and Ureteral Cancer established jointly by Japanese Urological Association and The Japanese Society of Pathology in 1990. The over-all survival rates at 1 and 3 years were 91.2% and 74.0%, respectively. The 3 year survival rates of TS and TE were 80.5% and 41.7%. As for grading, the 3-year survival rates were 75.0% for G1, 70.1% for G2, and 75.2% for G3, respectively. The stage of the tumors affected the prognosis. Of 88 patients 26 (Group 1) received cisplatin based combination chemotherapy as a postoperative adjuvant therapy, and the remaining 62 (Group 2) received no such cytotoxic adjuvant chemotherapy. The 3-year survival rates were 63.3% in Group 1 and 78.9% in Group 2, however mean age of Group 1 was significantly younger than that of Group 2. In spite of the age matched trial, there were no significant differences in survival rates between both groups. Adverse effects of cisplatin based combination chemotherapy included gastrointestinal symptom, fatigue, alopecia and leukopenia, however no serious toxicity was seen. These results suggest that prospective randomized trial would be clarified the efficacy of postoperative adjuvant chemotherapy for patients with renal pelvic and/or ureteral cancer. PMID- 1921023 TI - [A case of renal pelvic squamous cell carcinoma accompanied with humoral hypercalcemia of malignancy]. AB - A 74-year-old male was urgently admitted to our hospital because of consciousness disturbance. Laboratory data showed remarkable hypercalcemia (7.8 mEq/L), hypophosphatemia, low % TRP, low intact PTH level, normal nephrogenic cyclic AMP and normal 1,25 (OH)2D level. Serum bone Gla protein, which was thought to express osteoblastic activity, was low. Serum tartarate resistant acid phosphatase and urinary excretion of hydroxyproline, which were thought to express osteoclastic activity, were high. CT scan showed an enlarged mass in the left renal pelvis, which was found to be a squamous cell carcinoma (SCC) by biopsy through percutaneous nephroscopy. Bone scintigram appeared normal. Therefore, we diagnosed it as renal pelvic SCC with humoral hypercalcemia of malignancy (HHM) and performed left nephrectomy. After nephrectomy, serum calcium returned to normal. But after a few weeks, lung metastasis appeared and serum calcium was reelevated. As to PTH related protein (PTHrP) which was thought to induce HHM, PTHrP content of the resected tumor measured by RIA assay was 13 pmol/g wet weight of tissue, which suggested that this tumor might have been producing PTHrP. PMID- 1921024 TI - [Gastrocystoplasty]. AB - In two female patients with severe radiation cystitis, aged 69 and 62 years, the bladder was augmented by an operationally resected segment of the gastric body. The segment, which was vascularized by the right gastroepiploic vessels, was anastomosed to the dome of the bladder. Both ureters were implanted to the gastric segment in one patient. Convalescence was uneventful. No gastric or urinary complication developed. Eight and two months postoperatively both patients were continent of urine and able to urinate satisfactorily. We believe that a gastric segment is a suitable alternative to an intestinal segment in reconstructing the urinary tract. PMID- 1921025 TI - Administration of intravenous conscious sedation in the emergency department. PMID- 1921026 TI - Nursing diagnosis: communication, impaired. PMID- 1921027 TI - Treating nursing's response to nursing diagnosis. PMID- 1921028 TI - Appropriate dosage of acetominophen for infants. PMID- 1921029 TI - Methods for obtaining patient follow-up information requested. PMID- 1921030 TI - Note from a Desert Storm nurse. PMID- 1921031 TI - Differences and similarities in practice between the United States and the United Kingdom. PMID- 1921032 TI - Everyone deserves a competent, compassionate nurse at the bedside. PMID- 1921034 TI - A different view of diploma nursing issue. PMID- 1921033 TI - Blame the victim? PMID- 1921035 TI - Emergency nurse develops coloring book and encourages others to "try their wings". PMID- 1921036 TI - A 49-year-old man with successful conversion of paroxysmal supraventricular tachycardia after adenosine administration. PMID- 1921038 TI - Comprehensive quality assurance in a level II trauma center emergency department. AB - QA is a logical, interesting, and rewarding process, from which many benefits can be derived if a positive approach is taken. The process is undoubtedly time consuming, and staff involvement, and administrative commitment to providing required resources are critical to ensuring improvements in care. PMID- 1921037 TI - A 21-year-old woman with rapid atrial fibrillation after adenosine administration. PMID- 1921039 TI - Rapid admixture blood warming. AB - A new technique of admixture blood warming allows rapid warming of packed red blood cells by the addition of heated saline. Each 4 degrees C unit of packed red blood cells is mixed with 250 ml of 70 degrees C saline. Diluted blood at 37 degrees C is ready for transfusion in less than 30 seconds. PMID- 1921040 TI - Response of the New Mexico Disaster Medical Assistance Team in St. Croix after Hurricane Hugo. AB - Our DMAT pulled together with the energy, flexibility, and adaptability necessary to make things work. Sally Coan expressed it best, saying, "I was with a group of people who would do anything [that was] needed." Dedication and trust within the DMAT helped create lasting friendships. The islanders were appreciative and we formed attachments to them that made them too dear to leave without sadness. The DMAT did leave, but we left in place an established medical system that the island would not otherwise have had a standard of care of which we felt proud. PMID- 1921041 TI - Poor emergency department record keeping may hamper legal defense. PMID- 1921042 TI - Exercise-related rhabdomyolysis and renal failure. PMID- 1921043 TI - Development of a nursing process-based documentation system. PMID- 1921045 TI - Injury prevention: from outrage to action. PMID- 1921044 TI - Starting intravenous lines in children: tips for success. PMID- 1921046 TI - The violence of war: a nurse veteran reflects. PMID- 1921047 TI - The worst thing. PMID- 1921048 TI - Kids and fire: a fatal attraction. PMID- 1921049 TI - Emergency Nurses Association position statement. Infectious diseases and the emergency care setting. PMID- 1921050 TI - Security dogs in the emergency department: one hospital's solution to the crisis of violence. PMID- 1921051 TI - An emergency nurse's Thanksgiving. PMID- 1921052 TI - Notes on the "violence in the emergency department" theme issue. PMID- 1921053 TI - Who will the heroes be? PMID- 1921054 TI - Violence in the emergency department: asking the right questions. PMID- 1921055 TI - Violence and assault: part of the job? PMID- 1921056 TI - Violence in the accident and emergency department: differences across the Atlantic. PMID- 1921057 TI - Rural ED staff also at risk. PMID- 1921058 TI - A flight nurse's dilemma. PMID- 1921059 TI - Violence in the emergency department: California's response to tragedy. PMID- 1921060 TI - Nurses in violence-prone emergency department seek solutions. PMID- 1921061 TI - A "consumer's report" for medical devices. PMID- 1921062 TI - Open-classroom, self-paced in-service idea for infrequently used ED equipment. PMID- 1921063 TI - More on tick bites. PMID- 1921064 TI - Trauma in pregnancy: uterine rupture. AB - Trauma during pregnancy is a unique situation. Understanding injury patterns, anatomic and physiologic changes, and the initial approach to resuscitation is essential for all emergency nurses. Maternal resuscitation is the only means of fetal resuscitation. Meticulous attention must be given to the ABC's, with some minor modifications. Cervical spine immobilization is done in conjunction with positioning on the left side. Oxygen is used liberally, but may not benefit the fetus if hypovolemia exists. IV access and aggressive fluid resuscitation should proceed quickly. Diagnostic testing, including radiologic evaluation, is performed as necessary--the mother's life must not be jeopardized on the basis of fetal risk. Continuous fetal monitoring should be instituted, even with seemingly minor injuries. In the rare event of maternal arrest, a postmortem cesarean section may be lifesaving for the infant. Policies should be formulated jointly by ED, obstetric, and neonatal staffs in advance to speed this difficult decision making process. The keys to survival, for both mother and infant, are an organized approach to resuscitation and teamwork among all professionals. PMID- 1921065 TI - The extent, nature, and response to victimization of emergency nurses in Pennsylvania. AB - A survey of 124 emergency departments documents the existence of significant victimization of emergency nurses. Data reflect an increased incidence of violence associated with urban settings, night shifts, shifts more than 8 hours long, patients who are intoxicated, patients who have medical conditions such as dementia or cerebral trauma, and male emergency nurses. After victimization, almost 15% of responding nurses had considered transferring to another unit; almost 18% had considered leaving nursing altogether. PMID- 1921066 TI - Dealing with violent patients in flight. AB - Prevention is the key to minimizing the dangers in aeromedical transport of violent patients. Complete patient evaluation, identification and treatment of underlying causes of the behavior, anticipation of possible behavior changes, and thorough preparation are needed to ensure a safe transfer. PMID- 1921067 TI - Blaming the victim: complex (nonlinear) patterns of causal attribution by nurses in response to vignettes of a patient assaulting a nurse. AB - When 60 staff nurses at a Veterans Administration hospital were asked to respond to vignettes in which a nurse is subjected to varying degrees of assault, blaming the nurse was at its highest level in response to the mild assault vignette, rather than to the extreme conditions (no physical contact or severe physical assault). When asked directly who was to blame for the assault in the vignette, not one nurse cited the patient. PMID- 1921068 TI - An emergency department shooting of a prisoner/patient under guard: lessons learned. AB - When an ED prisoner/patient was shot, the unfortunate incident offered a number of lessons, even for a busy, seasoned emergency department with good security. These lessons, not the least of which was to think twice before removing both handcuffs, are worth sharing. PMID- 1921069 TI - Hostage-situation policy statement for the emergency department. PMID- 1921070 TI - Restraining potentially violent patients. AB - People who are emotionally distraught or mentally ill are rarely predictable. A calm, reassuring, but firm and decisive manner is most effective in dealing with out-of-control patients. Staff members should be careful to never position themselves with a potentially violent or distraught patient between them and the door. A room should be emptied of all extraneous, potentially dangerous objects before restraint of a patient. A clear plan of what is to be done and who is to do what is necessary. All staff members should remove glasses, pens, scissors, and other items that are potential weapons before restraining a patient. A humane attitude when restraining patients is extremely important. Sometimes the attitude of those applying restraints can be more traumatic than the actual application of the restraints. It is important that staff members remember that patients who need restraint are not "bad" people. For whatever reason, they have lost the ability to control themselves. These people do not like being out of control; given a choice, they would choose not to be. The staff attitude during this stressful event, which is becoming all too common in the emergency department, can have a tremendous effect on patients who require this procedure. When a patient is restrained in a competent, humane manner, staff members can pride themselves on their skills in dealing successfully with this emergency, just as they can when dealing with a cardiac arrest. Finally, it has been said that you cannot truly understand what another person is going through until you have had the same experience yourself.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921071 TI - Violence in Philadelphia emergency departments reflects national trends. PMID- 1921072 TI - Weapons in the emergency department. PMID- 1921073 TI - The golden hour: trauma center standards in nontrauma-center emergency departments. PMID- 1921074 TI - Fatal shooting by an ED patient/prisoner during a preplanned escape. PMID- 1921075 TI - An approach to the potentially violent patient. PMID- 1921076 TI - Violence in a pediatric emergency department: lessons learned from one experience. AB - A multitude of forces influence the probability of violence in an emergency department, but none impact as directly as the skilled response of the emergency nurse. It is important not to overlook the availability of security and law enforcement, but it may be equally important for nurses to take appropriate steps toward preventing or solving such problems with a minimum of physical and emotional pain for all concerned. With time and practice, incidents of violence can be replaced with opportunities for growth and healing. PMID- 1921077 TI - Emergency nurses in the field: Fleet Hospital number 5, eastern Saudi Arabia. PMID- 1921078 TI - Creating a patient care outline: vaginal bleeding. PMID- 1921079 TI - Rural trauma: the next trauma system challenge. PMID- 1921080 TI - Chest pain and syncope in a 47-year-old man. PMID- 1921081 TI - Suddenly, I am exposed: an emergency nurse's nightmare. PMID- 1921082 TI - Impressions. Risk (risk), n. hazard; danger; peril; exposure to harm. PMID- 1921083 TI - Unusual incident: code orange. PMID- 1921085 TI - On the home front: a reservist's Desert Storm experience. PMID- 1921084 TI - From "June Cleaver" to active duty. PMID- 1921086 TI - Lessons learned: MasCal in the field, Saudi Arabia. PMID- 1921087 TI - Desert Shield nurse: firsthand account. PMID- 1921088 TI - A look at our new emergency department: South Shore Hospital, South Weymouth, Massachusetts. PMID- 1921089 TI - Emergency Nurses Association position statement. CEN credentialing and review courses. PMID- 1921090 TI - Emergency Nurses Association position statement. Telephone advice. PMID- 1921091 TI - [Active bronchial tuberculosis--a clinical study on 36 cases]. AB - A total of 36 patients (16 male and 20 female) with tracheobronchial tuberculosis were admitted during the last nine years and were evaluated for their clinical features. The chief complaint in three quarters of the patients was intractable cough, in particular, in those with tracheal tuberculosis. One of three patients who suffered from wheezing was prescribed steroid, being diagnosed as having bronchial asthma instead of tuberculosis. Plain chest X-rays of two patients revealed no abnormality. Pleural effusion was observed in three patients, and miliary tuberculosis in two patients. Bronchial biopsy was carried out in 23 patients, however, in only 11 patients a histopathological diagnosis of tracheobronchial tuberculosis could be made. In contrast, in all 36 patients smear and/or culture for tubercle bacilli were positive. Therefore, bronchial biopsy was considered not to be essential in making a definite diagnosis of bronchial tuberculosis, although it did not exacerbate the lesion to lead to endobronchial stenosis. Only seven out of 36 patients were in the habit of smoking but three of the four had already broken the habit at least one year before being diagnosed as having the disease. The remaining four patients were still smoking but less than 10 cigarettes a day, with one exceptional patient who was smoking 30 cigarettes on average a day. It has been well known that there is a sexual difference in the incidence of bronchial tuberculosis, namely among females with relatively low population of smokers, the incidence is high. Another probable reason for the higher female incidence is assumed to be due to the structural susceptibility of the bronchus with smaller diameter lumen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921092 TI - [The incidence of pulmonary tuberculosis in an urban area]. AB - The incidence and prevalence of pulmonary tuberculosis has declined steadily in Japan, but the trends differ greatly by area according to epidemiological status. We studied the incidence and trends of pulmonary tuberculosis in an urban area (population approx. 150,000) during the period of 1979-1988. The area studied is a part of a large commercial city, characterized as having the most prevalent rate of tuberculosis area in that city. Of 1245 newly registered cases, 80% were over 40 years of age. While the incidence rate decreased to 57% in the last 10 years in this area, compared to 69% decrease for all of Japan, it was still considerably higher than the national average. Especially in the 20-59 age group it continued to be 2 times higher than that of the whole of Japan. Moreover, the positive rate of tubercle bacilli at the time of registration had increased remarkably from 27% in 1979 to 62% in 1988. These results suggest the tuberculosis continues to be a significant problem in this urban area, although the steady decline in the incidence of tuberculosis had led to a lack of awareness of this disease. PMID- 1921093 TI - [Clinical significance of serum CA125 in patients with tuberculous pleurisy]. AB - We measured CA125 levels of the sera and pleural effusions in both patients with tuberculous pleurisy (TB) and with benign non-tuberculous pleurisy (non-TB). In all the TB patients, serum CA125 levels were increased (78 to 370 U/ml, mean +/- SD = 167.3 +/- 96.8 U/ml, n = 8), and were significantly higher than those in non TB patients (167.3 +/- 96.8 U/ml v.s. 36.9 +/- 18.4 U/ml, p less than 0.01). Neoplastic diseases or gynecological disorders were not found in these patients. On the other hand, either CA125 or LDH levels of pleural effusions were not significantly different between these two groups. Although adenosine deaminase (ADA) levels in pleural effusions were also significantly higher in the TB patients (p less than 0.05), there were no correlation between serum CA125 and ADA levels in pleural effusions. Serial measurement of serum CA125 levels in the TB patients revealed that serum CA125 levels were markedly decreased one to two months after anti-tuberculous therapy (172.6 +/- 103.3 U/ml to 23.3 +/- 9.9 U/ml, p less than 0.01). It is suggested that the measurement of serum CA125 in patients with tuberculous pleurisy is useful as an indicator of disease activity. PMID- 1921094 TI - [Blood gas changes during treadmill exercise in convalescents from pulmonary tuberculosis. 2. Clinical results]. AB - We reported earlier in the 1st report the use of treadmill walk apparatus and transcutaneous blood gas measurement apparatus as a newly designed exercise test. In this report, test was carried out in 90 persons (4 healthy, 66 recovered from pulmonary tuberculosis, 3 recovered from silico-pulmonary tuberculosis, 12 of COPD, and 5 of pulmonary fibrosis et bronchiectasis). The changing curves of transcutaneously measured O2 partial pressure (tPo2) were, as previously reported, classified into 4 types: 1. unchange-6, 2. slightly decreased-38, 3. moderately decreased-24, 4. markedly decreased-21. And unexpected odd curves were seen in 4 patients, 3 of whom were retested the other day, and their changing curves of tPo2 in the second test were corrected and classified into slightly or moderately decreased type. The decreasing slopes of 4 types of tPo2 curves were subclassified, in each type, into 3 to 4 forms. In recovered pulmonary tuberculosis patients, in general, when the spread of pathologic changes in the lungs was wider, the more decreased types of tPo2 curves were seen. But in COPD patients, such was not the case. In the exercise test, total tolerance time (minutes) against the definite load was significantly shorter in the more decreased type; unchanged-13.5-14.5, slightly decreased -7-10, moderately decreased-6-9, and markedly decreased-3-5. The recovering time of tPo2, pulse rate, blood pressure etc. from the records in the end of the exercise to the pre exercise records, was longer in the more decreased type. On the other hand, usually the lower Pao2 of the patients were, the more their changing curves of tPo2 decreased. Pao2 was previously measured in blood taken from brachial artery in supine position before the test. But exceptionally in some patients with high Pao2 value, the curves belonged to markedly decreased type. The changes of oxygen values of some patients during exercise test were individually different, showing that this exercise test reflected their comprehensive respiratory function. Prognosis was especially bad in patients with markedly decreased type, 8 of whom had died from respiratory failure within 2 years after the test. In conclusion, it can be said that this exercise test was effective in judging the pulmonary reserve function and the prognosis in recovered pulmonary tuberculosis patients, but more detailed investigations are necessary, especially in more COPD patients, for the understanding of the respiratory distress.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1921095 TI - [A case of tuberculous mesenteric lymphadenitis detected by abdominal symptom after 4 months' antituberculous chemotherapy against pulmonary tuberculosis]. AB - We reported a case of tuberculous mesenteric lymphadenitis. A twenty three year old man was admitted to our hospital with pulmonary tuberculosis on May, 1988. Chest X ray findings improved after 4 months' antituberculous chemotherapy, but he complained of right lower abdominal pain and a mass with tenderness. Barium series of gastro-intestinal tract showed evidence of extrinsic compression on the intestine. Abdominal CT showed rim enhancement and a multiloculated appearance, and the ultrasonography showed a hypoechoic mass. But we did not make a definite preoperative diagnosis, therefore exploratory operation was done. An abscess with caseous granuloma was found in the mesenteric lymphnodes removed at laparotomy. PMID- 1921096 TI - [Enzymatic profile of Mycobacterium avium and Mycobacterium intracellulare]. AB - The characterization of extracellular enzymatic activities of Mycobacterium avium and Mycobacterium intracellulare which were identified by DNA probe (Gen-Probe, Cal., USA) was carried out using the API ZYM system (API, La Balme Les Grottes, France). The enzymatic activities of M. avium were attributed to esterase (C4), esterase lipase (C8), leucin arylamidase, acid phosphatase and phosphoamidase. Enzymatic characterization of M. intracellulare was very similar to that of M. avium. However, M. intracellulare differed from M. avium in the following two points: (i) Alkaline phosphatase activity was demonstrated, (ii) Acid phosphatase activity was much stronger. PMID- 1921097 TI - [Effect of shift interval for the clinical nurse with respect to circadian rhythm]. AB - Circadian rhythm is entrained in the 24-hour time interval by periodic factors in the environment, known as zeitgeber. But most rotating work schedules are outside the range of the entrainment of the pacemaker timing the human circadian sleep wake cycle. It has been postulated that physiological and emotional disturbances occur in most human functions when the circadian rhythm is disturbed. So application of circadian principles to the design of shift schedules can aid in maintaining the temporal integrity of the circadian system and thereby minimize for the shift worker any detrimental consequences of circadian disruption. This study was a quasi-experimental study to test the effect of shift intervals for the clinical nurse on the circadian rhythm. Twenty nurses newly employed in general units of two hospitals were selected as an experimental group and twelve college nursing students as a control group. Both groups were selected according to an established criteria using a purposive sampling technique. Ten subjects were assigned to a weekly shift group and another ten to a biweekly shift group engaged in a semi-continuous shift schedule (sunday off) with a backward direction; that is, morning-evening-night shift. The control group worked a morning shift for 42 days. Oral temperature rhythm, waking time, sleep-wake cycle, fatigue, and mental performance were measured during the experimental period. The data collection period was from April 30, 1990 to June 10, 1990. MANOVA, paired t-test, ANOVA, and Student Newman Keuls method were used for statistical analysis. The results are summarized as follows. 1. Phase delay in the acrophase of temperature rhythm was shown according to the backward rotating shift. A complete adaptation to work on the night shift was achieved between the sixth and ninth day of the night shift. 2. There was no difference in either waking time or sleep-wake cycle according to the duration of the working day for every shift group. Significant difference was found in the waking time and the sleep-wake cycle for subjects on the morning, evening, and night shift in both of the shift groups (weekly shift group: lambda = 0.121, p less than 0.01, lambda = 0.112, p less than 0.01, biweekly shift group: lambda = 0.116, p less than 0.01, lambda = 0.084, p less than 0.01). 3. There was no difference in fatigue between the first working day and the last working day for the control group and for the biweekly shift group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1921098 TI - [A study on the change of the primipara mother-infant interaction by infant's age in months]. AB - The intent of this longitudinal descriptive correlational study is to investigate the change of the mother-infant interactions over the periods of one month, three months and six months of the infant's age. This study is also intended to explore the interrelationships among three major factors--the perception of pregnancy, the mother-infant interaction and the maternal attitude. The samples participated are 36 pairs of mother and infant from two university hospitals in Seoul. A data collection was made, from October in 1988 to September in 1989, for each subject at five periods of time; prenatal period (after 36 weeks in pregnancy), postpartum two or three days, one month, three months and six months of infant's age. The research tools used in this investigation are Mother-Infant Play Interaction Scale (MIPIS), Prenatal Self-Evaluation Questionnaire and Cohler's Maternal Attitude Scale. Some of the findings are as follows; 1. There is a significant increase in the mother-infant interaction from one month to three months and six months of infant's age. The highest score of the mother-infant interaction during three periods is at the time of three months. 2. The primipara's mother-infant interaction is not affected by the demographic characteristics, such as age, education and vocation of mother, types of delivery, or sex of infant. 3. Among seven categories of the perception of pregnancy, the most positively perceived categories by primiparas are acceptance of pregnancy and identification of a motherhood role; whereas the negative ones are preparation for labor, concern for well-being of self and baby, and fear of pain, helplessness and loss of control in order of negativity. 4. There is no significant relationship between the perception of pregnancy and the mother infant interactions. 5. There is no significant change in the maternal attitude over the period of one month, three months, and six months of infant's age. 6. There is no significant relationship between the maternal attitude and the mother infant interactions. 7. The significant relationships are found between the perception of pregnancy and maternal attitude, especially in the categories of concern for well-being of self and baby, acceptance of pregnancy, identification of a motherhood role, fear of pain, helplessness and loss of control, and relationship with husband. In conclusion, it is confirmed that primipara's mother infant interactions change over time period, and that perception of pregnancy and the maternal attitude do not affect the mother-infant interactions despite a significant relationship between those two variables.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1921099 TI - [An exploratory study toward a theoretic construction of hope]. AB - A written association test has been conducted to establish the concept, the meaning and the process of hope. The test consists of the major question: List of three words related to "hope". The question was given to 55 nurses (rehabilitation/cancer/internal medicine care wards units) and 61 patients. A total of 289 words have been collected, and the collection was analyzed with categorization by the value or meaning of listed words. The analysis yields three major categories, namely, componants of hope, metaphores/symbols, and synonyms. The three major categories may be further partitioned into subcategories. The results are significant to define the nature of the hope and process of the hope. These understanding will facilitate the development of effective methods of nursing or chronic or cancer patients disabled. PMID- 1921100 TI - [Professional bureaucracy as an organization of design in nursing administration]. AB - Nursing, a profession, continues its efforts toward professionalization. Attention to efficiency and effectiveness of its organizational system must be balances with that of maintaining quality of care. The wise use of personnel is of particular concern. The structure of nursing's administrative organization is very important, because most nursing services are delivered through an organization. Professional bureaucracy is recommended for the structure and managerial strategy of nursing's administrative organization. Specifically, considerable decision-making in their work should be transferred to the staff nurses who provide professional nursing services in direct interaction with the public. The coordinative parameters of the system should be based on professional nursing knowledge. The premise required by this commitment would be built on the identification of nursing knowledge and intellectual and behavioral standard of nursing practice. PMID- 1921101 TI - [Correlations among body weight, life style and health status in Korean adults]. AB - Correlations among body weight and sociodemographic factors, including life-style were tested as social determinants of health in a sample of 5,201 adults in Korea. The aim of this study was to determine the extent to which sociodemographic variables and life-style associated health behaviors explain body weight distribution. A second aim was to explain the relation of body weight and health status to stress the importance of body weight as an early risk indicator of health status. The canonical correlation between the weight distribution (underweight and overweight) and the independent variables was 0.29, 17% of the total variance was explained. Perceived health level represented the highest contribution (canonical coefficient 0.82) to body weight. Sociodemographic factors such as sex, economic status, and life-style factors such as smoking, exercise, regular meals and sleep showed comparatively high contributions to body weight. The relevance of body weight for health status including the rate of chronic disease and the rate of medical utilization was significant. Especially, underweight was clarified as being more important than overweight to morbidity level and medical utilization. These findings suggest that perceived body weight is an important indicator of health status and is thus a valuable variable to be considered for nursing intervention and health education related to the promotion of health. PMID- 1921103 TI - [The relationship between and hardiness and psychosocial adjustment of persons with colostomies]. AB - The problem addressed by this study were to explore the effect of hardiness on psychosocial adjustment of persons with a colostomy and to identify factors which influence that psychosocial adjustment. The purpose was to suggest a theoretical base for the planning of supportive nursing interventions to increase the level of adjustment. Among members of the Korea Ostomy Association, 34 subjects who had undergone colostomy from March, 1990 to March, 1991 were selected as the sample. Data were collected from April 8 to May 8, 1991 using a mailed questionnaire. The instruments used for this study were the Health-Related Hardiness Scale (Pollock, 1984) and the Psychosocial Adjustment to Illness Scale (Derogatis, 1975). ANOVA, Pearson correlation coefficient and Stepswise Multiple Regression were used for data analysis. The results of the study are summarized as follows. 1. Hardiness was significantly related to psychosocial adjustment (p = 0.009). That is, the higher the hardiness, the higher the level of psychosocial adjustment. 2. Among the demographic variables, only economic level was significantly related to the level of psychosocial adjustment. (p = 0.005). 3. The important factors influencing the level of psychosocial adjustment of persons with a colostomy were economic level, commitment, challenge (subconcepts of hardiness). Therefore, in order to increase the level of the psychosocial adjustment, it might be helpful to provide them with hardiness training to strengthen their commitment and their challenge. PMID- 1921102 TI - [Effect of lateral position and chest percussion on pulmonary gas exchange in patients with decreased level of consciousness]. AB - The purpose of this study is to verify the effect of lateral position and chest percussion on gas exchange in the decreased level of conscious patients. The Subjects for this study were 21 patients 'admitted in ICU of CNUH from Dec 18th, 1989 to Aug 4th, 1990. The Data was analyzed by paired t-test. The results of this study as follows: 1) In comparison of supine position, good-lung dependent position and good-lung dependent with chest percussion, the difference of PaO. was statistically significant (P less than 0.05). 2) In comparison of supine position, good-lung dependent position and good-lung dependent with chest percussion, the difference of A-a Do. was statistically significant (p less than 0.05). In conclusion, the use of good-lung dependent position and chest percussion was effective nursing intervention on decreased level of conscious patients in ICU. PMID- 1921104 TI - [A study on the pattern of pain expression of peptic ulcer patients]. AB - Pain is a subjective and multidimensional concept. Therefore the patient's expression of pain have been referred to the best believable indicator of pain condition but the support data obtained from the patient considered cultural difference is a deficient condition in determined on the precise nursing diagnosis. The purpose of this research was to understand multiple pain responses in cultural difference and sensitivity, to encourage communication between medical teams, and to provide the foundation data of on data of precise nursing assessment for the patient in pain. The research problem was to grasp pain express pattern of Korean peptic ulcer patients. The subjects were 20 peptic ulcer patients in medical unit or OPD of twp university hospitals in Seoul. Data were collected from September 7th to 22nd, 1990 by intensive interviews. Interviews were done by the researcher and all were tape-recorded. The Data analysis was done by Phenomenological method from Van Kaam. Validity assured by confirmation of the internal consistency of the statements and category by nursing colleague in educational and clinicians in medical care. From the emic data, 96 descriptive statements were organized in 18 theme cluster. The results of study were summarized as follows. 1. Pain Express Pattern cluster of Peptic Ulcer Patients were "pain as clogging", "shallow pain", "pain as pressing", "nauseateing pain", "pain as smarting", "pain as pulling", "pain as pricking", "pain as bursting", "wrenching pain", "excising pain", "uncontrollable pain for mind and body", "awakening pain", "pain as hollowing" and the other cluster. As above mentioned, Pain Express Pattern of Peptic Ulcer Patient appeared diversely in verbal and they were propered to Korean culture. Therefore they will provide for the foundation data of precise nursing assessment. PMID- 1921105 TI - [Signal-averaged ECG and left-ventricular function in patients with severe ventricular arrhythmia in ischemic heart disease]. AB - In 35 patients with ischemic heart disease we evaluated the incidence of ventricular late potentials and left ventricular function. The patients were divided into two groups: group A consisting of 15 patients (14 men, 1 woman) aged from 40 to 71 years (mean age 56) with previously documented ventricular tachycardia or fibrillation, and into group B comprising 20 subject (16 men, 4 women) aged from 35 to 62 years (mean age 50) with ischemic heart disease without the above-mentioned arrhythmias. Time from the development of ventricular tachycardia or fibrillation was 3 weeks to 4 years. The incidence of arterial hypertension and previous myocardial infarction was similar in both groups. Body surface late potentials were recorded by signal averaging technique according to Simson using Frank's orthogonal XYZ lead system. In addition, in all the patients 24-hour ECG monitoring was performed to reveal any ventricular rhythm disturbances and echocardiography was used to evaluate left ventricular function. The presence of the ventricular late potentials meeting at least two of the Simson's--Dene's criteria was found in 13 (87%) patients in group A and in 2 (10%) patients from group B. In the patients after ventricular tachycardia or fibrillation the mean values of th total QRS duration (QRS-D) and the low amplitude signal duration (LAS40) were higher whereas the root mean square voltage of the last 40 ms of th vector magnitude QRS (RMS) was lower (154 ms, 56 ms, 15 muV, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921106 TI - [Indications for emergency cardiovascular surgery at the Institute of Cardiology]. AB - Between 1981 and 1989 73 patients (46 males, 27 females aged 15-69; mean 42) underwent emergency cardiac operation in the I Clinic of Cardiosurgery. There were 39 (53%) patients with valvular disease, 18 (25%) with prosthetic valve dysfunction and endocarditis, 9 (12%) with acute aortic dissection (2 of them had Marfan's syndrome), 5 (7%) with atrial myxoma and 2 (3%) with malignant pericardial mesothelioma. All of them were treated in C.C.U. before surgery. 27 urgent operations were performed within the first 24 hours after the admission to C.C.U. 30 of 73 patients died (41%). The IV NYHA functional class was stated as the most significant predictive factor for in-hospital mortality. The greatest mortality was observed in the group of patients with valvular disease (53%). In hospital survival rate reached 50% after reoperations as a procedure of choice in prosthetic valve dysfunction. Good early results were observed in patients with aortic dissection (survival rate--66%). The presence of Marfan's syndrome was associated with a poor surgical prognosis. There were no deaths after atrial myxoma removal, but all patients with malignant mesothelioma died. The most common cause of all deaths was congestive heart failure. PMID- 1921107 TI - [Causes of occurrence of wave V of pulmonary wedge pressure in patients with acquired heart valve diseases]. AB - It is believed that a significant V wave in pulmonary capillary wedge pressure (PWP) is a sign of mitral regurgitation. Of 358 patients with acquired valvular heart disease in 24-cases a significant V wave (15 mm Hg of PWP) was recorded during right heart catheterization. All patients underwent right heart catheterization with a flow- directed, balloon-tipped, thermodilution catheters (Edwards Labs). Mean pulmonary, capillary wedge, and right atrial pressures were monitored and recorded. Cardiac output was determined by thermodilution technique using iced 5% dextrose. After measurements of flow, pulmonary and systemic resistance morphology of V wave from PWP recordings was assessed. We measured dp/dt of the ascending limb of V wave and Libanoff and Rodbard V wave index (dp/dt:CI). Nine patients with significant V wave had no signs of mitral regurgitation and had mainly significant mitral stenosis (group III). Group II (6 patients) consisted of patients with different combinations of acquired left heart valve disease and mitral regurgitation. Group I (9 pts) consisted of patients with isolated mitral regurgitation. There were no differences in right atrial, pulmonary, and capillary wedge pressures, cardiac index, pulmonary and systemic valvular resistance among groups I, II and III. There were significant differences as far as dp/dt V wave was concerned (gr I--136 +/- 31.4, gr II- 112.2 +/- 30.7, gr III--72.7 +/- 31.2 mm Hg/s). Libanoff's index of V wave was also significantly different in all three groups--gr I--12.7 +/- 6.2; gr II--8.0 +/- 2.3; gr III--4.8 +/- 1.7 mm Hg/s). It seems that V wave in PWP recordings is not only a sign of mitral regurgitation, but also could be a sign of decreased pulmonary veins compliance. PMID- 1921108 TI - [Does coronary surgery prolong life--or only improve its quality?]. PMID- 1921109 TI - [Non-Q wave myocardial infarction. Recurrent myocardial infarction, unstable angina and arrhythmia in 8-year observation]. AB - The contradictory views on long term clinical course of patients after non-Q wave myocardial infarction (NQMI) as compared with those after Q wave myocardial infarction (QMI)--induced us to undertake a comparative study of both types of myocardial infarction during a 8 year follow-up. The study was carried out in 400 patients (pts) with NQMI (mean age 51) and 485 pts with QMI (mean age 53). Both groups were compared. We have analysed the following parameters: the dynamics of ischaemic heart disease (unstable angina, reinfarction, arrhythmias, mortality) and coronary arteriography. During 8 year observation unstable angina and arrhythmias, were statistically more frequent in pts after NQMI. Recurrent myocardial infarction occurred in 196 (49%) of pts after NQMI and only in 87 pts (18%) after QMI (p less than 0.001). However, the difference in mortality between both groups was not significant (37% vs 39% respectively). Coronary angiography was performed at 1-6 months after myocardial infarction. In 65% of pts after NQMI detected lesions were limited to proximal part of one or two coronary arteries. CONCLUSION: NQMI is characterized by unstable long-term clinical course, and that is why pts with NQMI should be recommended for early coronary angiography and revascularization. PMID- 1921110 TI - [Comparative study of acute and chronic effects of nifedipine in patients with secondary pulmonary hypertension]. AB - The effects of nifedipine in a single dose of 10 mg on the pulmonary circulation and the selected right and left ventricular function indices were studied in a group of 10 patients with secondary pulmonary hypertension (mean systolic pressure 55.2 mm Hg). In 8 patients hemodynamic studies were repeated after seven days treatment (3 x 10 mg). Acute treatment with nifedipine resulted in a reduction in mean systolic arterial pressure by 21.8%, diastolic by 12.2% and systemic resistance by 25.5%, and in an increase in cardiac index by 14.3%. After 7 days a similar pattern of changes was observed, however with less intensity: systolic pressure was reduced by 10.3% diastolic by 5.5%, and systemic resistance by 17.1%. Pulmonary artery wedge pressure did not change after a single dose, and mean pulmonary artery pressures showed a tendency toward lower levels: systolic by 8.9% and diastolic by 8.6%, whereas total pulmonary resistance decreased markedly (by 22.7%), as well as pulmonary vascular resistance. Right ventricular filling pressure was reduced. After chronic treatment we found a further slight fall in the pulmonary arterial pressure. Although per cent changes were similar to those in the arterial pressure, alterations in the mean values were not statistically significant. The total pulmonary resistance remained reduced. While analysing the changes in the pulmonary circulation and right ventricular indices it should be noted that they were less intense and less homogeneous than the left ventricular function parameters. Some of the patients showed certain similarities in the direction and intensity of changes in the hemodynamic indices of the pulmonary circulation in the acute and chronic experiment. PMID- 1921111 TI - [Evaluation of hemodynamic changes in patients with primary arterial hypertension after treatment with a combination of pindolol and clopamide (Viskaldix)]. AB - In 35 patients with mild essential hypertension the influence of 9 week Viskaldix therapy on hemodynamics was evaluated. Twelve of them underwent repeated hemodynamic examinations after mean 13 months treatment. Viskaldix therapy lowered total peripheral resistance --TPR and there was no significant influence on the heart rate, stroke volume, and cardiac output. It was demonstrated that decrease of total peripheral resistance after treatment with Viskaldix was directly proportional to the initial values of TPR. PMID- 1921112 TI - [Stenosis of the left arterial outlet (aortic stenosis)]. PMID- 1921113 TI - [Mitral stenosis]. PMID- 1921114 TI - [When should aortic valve insufficiency be surgically treated?]. PMID- 1921115 TI - [Indications for surgical treatment of mitral valve insufficiency]. PMID- 1921116 TI - [Myocardial reperfusion injury. The role of free radicals and xanthine oxidase]. PMID- 1921118 TI - [Detection and prevention of risk factors of ischemic heart disease in children and adolescents--a prospective approach to present-day cardiology]. PMID- 1921119 TI - [Clinico-hemodynamic characteristics of patients with initial signs of hypertension]. AB - Multifactor analysis was used to make clinical and hemodynamic comparisons in 42 patients with borderline arterial hypertension, 27 with Stage I hypertension, 40 with Stage II hypertension, and 40 healthy persons. Central hemodynamic parameters at rest and during graded bicycle ergometer exercise were measured by the Defares carbon dioxide return respiration method modified by V. L. Karpman. As compared with patients with hyperkinetic circulation, those with hypokinetic one were older, had a longer history of arterial hypertension, obesity, more common left ventricular hypertrophy, higher baseline diastolic pressures and total peripheral vascular resistance, less increase in cardiac index and greater enhancement of total peripheral vascular resistance during submaximal exercise. There was a clear-cut correlation between the progression of arterial hypertension and increase in values of factors I (clinical and hemodynamic) and III (cardiotonic). PMID- 1921117 TI - [Harmless heart sounds of combined origin]. PMID- 1921120 TI - [Restrictive cardiomyopathy in primary amyloidosis]. PMID- 1921121 TI - [Incidence of detection of coronary disease in patients with vasorenal hypertension of arteriosclerotic etiology]. AB - The paper provides strong evidence for the fact that it is essential to perform a bicycle ergometric test in patients with vasorenal hypertension irrespective of their elevated blood pressures. It also presents indications for selective coronary angiography. A detailed comprehensive examination of patients with vasorenal hypertension has revealed that 91.2% have a concurrent coronary artery lesion that requires surgical correction. PMID- 1921123 TI - [Clinical grading of paroxysmal atrial fibrillation in patients with ischemic heart disease]. AB - The study into the nature and severity of clinical and electrocardiographic manifestations of paroxysms of atrial fibrillation in 213 patients with coronary heart disease identified the basic clinical and instrumental ECG signs (subjective attack tolerance, transient ECG changes, onset of left ventricular failure) that correspond to four stages of the natural history of paroxysmal atrial fibrillation. The use of the grades in clinical practice allows one to more definitely evaluate the status of patients, to correctly choose their management policy, and to define indications for hospitalization. PMID- 1921122 TI - [A modulated type of ventricular parasystole]. AB - The paper presents data (from 15 case histories) and the methods for ECG analysis of ventricular parasystole of the modulated type with accelerated or delayed paracenter activity entrainment and annihilation phenomena. A relationship between classical and modulated types of parasystole is discussed. PMID- 1921124 TI - [Coronary venous blood flow in patients with acute myocardial infarction]. AB - In 94 patients with large myocardial infarction, their coronary venous blood flow was studied in the acute period of the disease by continuous coronary sinus thermodilution. No relationship was established between the coronary venous blood flow and the duration of coronary heart disease. The patients with anterior myocardial infarction had a significantly less blood flow in the vena cordis magna than those with posterolateral infarction. No correlation was found between the blood flow and precordial mapping parameters. Thus, continuous coronary sinus thermodilution cannot be used for indirect identification of the site of myocardial infarction and for prediction of its progression severity. PMID- 1921125 TI - [Macro- and microscopic anatomy of the heart conduction system in myocardial infarction]. AB - Morphological and morphometric examinations of the cardiac conduction system (CCS) of subjects who had died in different periods of acute myocardial infarction in the presence of atrioventricular block versus those without conduction disturbances have indicated that the severity of circulatory disorders leading to destructive processes in the ischemic myocardium, as well as involutional processes in its autonomic nerve terminals are essential in the development of functional abnormalities in CCS in myocardial infarction. The more profound the dysfunction of CCS is, the closer it is to the myocardial alteration foci. The altered CCS with the block recorded should be interpreted as its impact of ischemia in the presence of fibrosis and calcinosis of ventricular septal structures. PMID- 1921126 TI - [Origin of QS complexes in hypertrophic cardiomyopathy and acute myocardial infarction]. AB - Superficial cardiac ECG mapping was performed to examine 16 patients with acute myocardial infarction and 13 with hypertrophic cardiomyopathy who had electrocardiographic signs of focal myocardial changes (QS complex and/or abnormal Q wave). Deviation of instantaneous ventricular depolarization vectors in the direction opposite the malfunctioning myocardial portion that had partially or completely lost its electric activity was found to underlie the formation of QS complex in patients with acute myocardial infarction. In some patients with hypertrophic cardiomyopathy, an abnormal QS complex is attributed to sharp changes in central and end instantaneous depolarization vector orientation in the direction of the most hypertrophic septal portions, the location of a QS areas corresponding to variants of asymmetric septal hypertrophy. PMID- 1921128 TI - [Various problems of prevention of ischemic heart disease]. AB - Measures aimed at promoting health and preventing diseases form part of medical prophylaxis. Modifying the pattern of death causes has caused changes in applying approaches to implementation of preventive measures whose success largely depends on lifestyle, environment, nutrition and living conditions. It is necessary to change the population and community's attitude to health problems. There are reserves for enhancing the effectiveness of measures against coronary heart disease in medical institutions: improvement of physicians's training in prevention of diseases, active detection of patients with early CHD signs and subjects at a high risk for the disease, their timely adequate follow-up and multimodality drug and non-drug treatment. PMID- 1921127 TI - [Prognostic significance of post-infarction "silent" ischemia]. AB - To study the predictive value of silent ischemia, a total of 132 patients with first transmural myocardial infarction were examined, 69 had anterior and 63 had inferior myocardial infarction. On days 8-12 of onset of the disease, all the patients underwent loading two-dimensional echocardiography along with transesophageal pacing, as well as polyposition coronary angiography. According to the echocardiographic findings, 3 groups of patients were identified: 1) 34 (25.8%) with painful ischemia; 2) 37 (28.0%) with silent ischemia; 3) 61 (46.2%) with a negative test. Ischemic alterations were more frequently seen in inferior (73%) than in anterior (36.2%) myocardial infarction. The patients with painful ischemia showed a lower threshold of ischemia occurrence, more severe and prolonged ST segment depression, and greater extent of an asynergic area than did the patients with silent ischemia. A 1-5-year (mean 2.4) follow-up revealed that in terms of the risk for postinfarction angina, recurrent myocardial infarction and fatal outcomes, patients with silent ischemia represent an intermediate group between those with painful ischemia and those who have a negative load test. PMID- 1921129 TI - [Hemodynamics of the lesser circulation in patients with ischemic heart disease during acute obsidan test]. AB - During acute obsidan testing, the hemodynamics was evaluated in the pulmonary circuit and right heart cavities of 60 patients with Functional Classes III-IV exertional angina pectoris, by using two-dimensional and Doppler echocardiographies of the pulmonary artery. According to the left ventricular myocardial volume/mass ratio, the patients were divided into 3 morphofunctional types of coronary heart disease (CHD). All the patients were found to have diminished contractility and pump function in the left heart along with moderately elevated blood pressure in the left heart and compensatory hyperfunction in the right heart, which are largely evident in the hypertrophic morphofunctional type of CHD. The degree of pulmonary hypertension was related to the severity of left ventricular dysfunction, whereas in the dilated type it was associated with its contractile disorders. In patients with the dilated and mixed types of CHD, obsidan caused a marked decrease in pulmonary hypertension, while in those with hypertrophic CHD it promoted its slight increase. PMID- 1921130 TI - [Indicators of central hemodynamics in patients with arteriosclerosis obliterans of the aorta and arteries of the lower extremities]. AB - Sixty six patients with atherosclerosis obliterans of the lower limb arteries were found to have severe central hemodynamic disturbances that correlated with the site of impairment. Central hemodynamic changes appeared as increased cardiac output and stroke volume, shortened tension period and prolonged ejection period. Cardiac derangement occurred under unfavorable hemodynamic conditions, which was followed by its hypertension and dilatation. Instrumental signs of preclinical heart failure were revealed in patients with multisegmental lesions, which should be regarded as a risk factor in performing reconstructive plastic operations. PMID- 1921131 TI - [Use of food products containing polyunsaturated fatty acids of the omega-3 group in patients with disorders of lipid metabolism]. AB - The clinical efficiency of the ichtyenic oil obtained by processing some commercial fishes was explored. The oil was used as a supplement to foodstuffs: edible inchtyenic oil (EIO) in a daily dose of 30 g (containing 8.0 g omega-3 polyunsaturated fatty acids); dietary protein caviar (DPC) in a daily dose of 45 g (0.6 g omega-3 polyunsaturated fatty acids); an emulsified protein-and-fat product (EPFP) in a daily dose of 30 g (1.2 g fatty acids), EIO was given to 44 patients with dyslipidemia (Group 1), DPC to 12 (Group 2), and EPFP to 8 patients (Group 3). Following a month therapy, there was a decrease in total cholesterol (TC) by 12.2%, triglycerides (TG) by 28%, low density lipoprotein cholesterol (LDLC) by 9.4%, very low density lipoprotein cholesterol (VLDLC) by 20.0%, whereas high density lipoprotein cholesterol (HDLC) rose by 15.3% in Group 1. Group 2 showed 12.4 and 20.8% reductions in TC and TG, respectively. In Group 3, TC and TG fell by 7.1 and 8.7%, respectively. In the two latter groups, lipoprotein cholesterol remained unaltered. Thus, omega-3 polyunsaturated fatty acid-containing foods may be used to correct lipid metabolism disturbances in patients with atherogenic dyslipidemia. PMID- 1921132 TI - [Comparative evaluation of nutrition of healthy persons, patients with the preclinical stage of ischemic heart disease and in patients with marked coronary disease]. AB - A total of 92 males aged 28 to 55 years were examined. These included 28 apparently healthy individuals, 45 subjects with preclinical coronary heart disease and 19 patients with Functional Class I-II coronary heart disease. A special questionnaire was used to examine the dietary patterns of the subjects with preclinical coronary heart disease, i.e. those having no typical clinical signs of the disease, but showing signs of myocardial infarction during the maximum exercise testing and minimal coronary arterial changes at selective coronary angiography. The subjects, unlike healthy individuals and CHD patients, were found to have 1 or 2 meals a day, frequently late at night, consume large amounts of sugar and other candies, fatty milk products, butter, eggs; small quantities of vegetables, fruits, and fish, often put additional amounts of salt to their diet. The subjects, as patients with severe CHD but unlike healthy individuals, were shown to have hypercholesterolemia and display high low density lipoprotein and apo-lipoprotein B levels; apo B/apo A being more than 1. The above dietary patterns of subjects with preclinical CHD represent one of the causes of abnormal changes in the blood lipid profile, which result in further CHD development. PMID- 1921133 TI - [Painless myocardial ischemia in patients with iron deficiency anemia]. AB - Resting and bicycle ergometric ECGs were examined in 159 patients with iron deficiency anemia, including 100 treated with iron-containing drugs. ST segment depression in the patients undergoing exercise was regarded as a sign of silent myocardial ischemia which is common in anemic patients, its detection rate increases as the disease progresses. In patients with iron deficiency anemia, silent myocardial ischemia results in a substantial decrease of threshold intensity, has a negative effect on cardiac output both at rest and during exercise, and significantly slows down the recovery of cardiac performance during therapy. This should be borne in mind while solving problems in medial labour examinations and making rehabilitative measures in patients with the above abnormality. PMID- 1921134 TI - [Doppler-echocardiographic assessment of the degree of pulmonary hypertension and right-ventricular pressure in patients with ventricular septal defects]. AB - The study was performed in 53 children aged 3 months to 4 years who had ventricular septal defect. Systolic pressure in the right ventricle, pulmonary artery and the severity of pulmonary hypertension were determined by two way: 1) from arteriovenous shunt via ventricular septal defect before its surgical closure; 2) from systolic regurgitation via the tricuspid valve after its seal. Right ventricular diastolic pressure was measured by Doppler echocardiography using diastolic blood flow through the tricuspid valve. Before ventricular septal defect closure, the correlation ratio of Doppler echocardiographic to cardiac catheterization values was 0.76 and that of Doppler echocardiographic to intrasurgical manometry was 0.79. In the postoperative period, a catheter was left in the right ventricle in 14 children and its pressure was simultaneously measured by the blind method. The correlation was 0.97 for right ventricular systolic pressure and 0.89 for diastolic one. PMID- 1921135 TI - [Rheologic characteristics of blood in patients with chronic post-embolic pulmonary hypertension]. AB - Examination of blood rheologic properties in 38 patients with chronic ++post embolic pulmonary hypertension revealed an elevated blood viscosity at all shift rates and a reduced erythrocyte deformability. A close positive correlation was found between blood viscosity and perfusion deficit. Hemorheologic disorders in patients with chronic post-embolic + pulmonary hypertension are caused by pachyhemia and blood acid-base imbalance due to respiratory failure. They deteriorate pulmonary and systemic hemodynamic disturbances and contribute to progression of blood flow derangement. PMID- 1921136 TI - [Cardioprotective effect of combined use of coenzyme Q9 and cyclohexyladenosine in ischemia, reperfusion and acute myocardial infarction]. AB - Effects of coenzyme Q9 (25 mg/kg), N6-cyclohexyl adenosine (CHA, 100 micrograms/kg) and their combination were compared in rats with short-term or permanent ligation of the left coronary artery. The following parameters were evaluated in three series of experiments: 1) incidence and duration of ventricular fibrillation and tachycardia during coronary occlusion (10 min) and consecutive reperfusion (5 min); 2) contractility and electrical stability of the heart (ventricular fibrillation threshold) in animals with 2-day myocardial infarction; 3) ischemic myocardial mass after coronary occlusion (5 min) and necrotic tissue mass in 2-day myocardial infarction. The rats were given oral drugs 5 days and 2 hours before the study. All the experiments were performed in open-chest anesthetized (nembutal, 50 mg/kg) rats exposed to ventilation at room air. Both the coenzyme Q9 and CHA significantly reduced the incidence and duration of coronary occlusion and reperfusion arrhythmias, prevented cardiac contractile depression (heart rate.developed pressure) and increased ventricular fibrillation threshold). The effect of coenzyme Q9 was more marked than that of CHA. Coenzyme Q9 substantially reduced necrotic tissue mass while CHA diminished ischemic tissue mass. At the same time the total cardioprotective action of the Q9 + CHA combination was more pronounced than that of them used alone. PMID- 1921137 TI - [Use of taurine in the treatment of experimental congestive heart failure]. AB - The therapeutic effects of 2-aminoethanesulfonic acid (taurine) were tested in animals with congestive heart failure (HF) simulated by aortic valve damage. The drug given in a daily dose of 100 mg/kg for a month was shown to reduce mortality rates as compared to controls, to improve the animals' clinical condition, hemodynamic and myocardial contractility parameters. Taurine was found to exert a positive action on the heart response to stresses. The impaired response in the animals restored to heart rate stimulation, catecholamines and calcium loading. The mechanisms of the agent's action are discussed in the present paper. It is suggested that taurine-based taucard will be included into the arsenal of cardiotropic agents after its clinical trials are successfully completed. PMID- 1921138 TI - [Evaluation of the effectiveness of the program of primary prevention of arterial hypertension at an industrial plant based on a prospective epidemiological study]. AB - Whether the primary arterial hypertension prevention programme can be applied among employees of a Novosibirsk industrial enterprise within the framework of the second stage of the USSR Cooperative Study of Arterial Hypertension Control, is studied. For this, the authors used sodium-restricted diet concurrent with non drug therapy (physio-, balneo-, reflexotherapy and acupuncture), and active sanitary education. The 2-year prospective follow-up showed a sufficiently high efficiency of health measures: the incidence of borderline hypertension was reduced by 10.5% at the end of the study, blood pressures could be maintained at the level of the borderline and subnormal values in most patients with persistent hypertension, the patients at risk developed no persistent hypertension, cases. In a 20% blind sample from the matched population, the changes in the frequency of various blood pressures were insignificant during this period. PMID- 1921139 TI - [Hemodynamic mechanisms of the hypotensive effect of cobalt in anesthetized rats]. AB - Hemodynamic mechanisms of Co(2+)-evoked hypotension were studied in pentobarbital -anesthetised male Wistar rats. Bolus i.v. administration of cobalt sulphate (30, 90 and 270 mg/kg of Co) evoked dose-dependent hypotension followed by tachycardia and increase in left ventricular contractility index (dP/dt/P). Administration of beta-adrenoblocker propranolol (2 mg/kg) attenuated Co evoked (270 ug/kg) tachycardia and unmasked its cardiodepressive effects (dP/dt/P decreased by 11% and end-diastolic pressure increased by 55%). Cardiodepressive Co2+ effects were prevented by administration of verapamil (0.4 mg/kg). In the second group hemodynamic mechanisms of Co-evoked hypotension were studied with radioactive microspheres. Co2+ infusion (55 mg/kg) lowered blood pressure (in average by 11%) by decreasing total peripheral resistance (-25%). Cardiotoxic effects were obtained with a ++larger dose 80 mg/kg/min. It is concluded that Co decreased blood pressure by vasodilatator action and its cardiotoxic effects attenuated by sympathetic counterregulation and may be prevented by verapamil. PMID- 1921140 TI - [Effect of adaptation to continuous stress on the contractile function and electric stability of the heart]. AB - In the time course of 15-day stress of moderate intensity, rat experiments indicated that following a day there developed a complex of changes typical of acute stressor syndrome. Five days of post-stress , the stress-related cardiac syndrome ceased, bradycardia developed, the contractile function was limited, and the fibrillation threshold returned to the control values, which was shown to be associated with activation of the cholinergic stress-limiting system. Fifteen days later there was normalization of heart rate and cardiac contractility, the fibrillation threshold remained at the baseline level. PMID- 1921142 TI - [Continuous postgraduate training of physicians]. PMID- 1921141 TI - [Mechanisms of anti-atherogenic effect of probucol and the prospects of its clinical use]. PMID- 1921143 TI - [Results of the contest "Cardil (diltiazem) in clinical practice"]. PMID- 1921144 TI - [Diagnosis and treatment of dilated cardiomyopathy]. PMID- 1921145 TI - Global glomerular sclerosis and glomerular arteriolar hyalinosis in insulin dependent diabetes. AB - We studied the lesions of global glomerular sclerosis and arteriolar hyalinosis in 43 (29 females) insulin-dependent diabetes mellitus (IDDM) patients whose creatinine clearance (CCr) was greater than or equal to 45 ml/min/1.73 m2 and whose renal biopsies had at least 20 glomeruli available for study. These patients, ages 17 to 55 years, had IDDM for 7 to 32 (20 +/- 6, means +/- SD) years. CCr ranged from 47 to 139 (91 +/- 25) ml/min/1.73 m2 and urinary albumin excretion (UAE) from 5 to 3386 (median = 127) mg/24 hrs. Eighteen patients were hypertensive. Thus, these patients represented a broad clinical range from normal renal function through overt diabetic nephropathy. The percent of glomeruli which were globally sclerosed was strongly correlated with CCr (r = -0.64, P less than 0.0001) and log UAE (r = +0.67, P less than 0.001). Hypertension was more common in patients with more than 10% sclerosed glomeruli (chi square = 9.5, P less than 0.002). Percent sclerosed glomeruli was highly significantly correlated with the index of severity of the arteriolar hyalinosis lesion (r = +0.66, P less than 0.0001) and mesangial volume fraction (r = +0.61, P less than 0.0001). We hypothesize that arteriolar hyalinosis could contribute to global glomerular sclerosis through severe compromise of glomerular blood flow. Alternately, global glomerular sclerosis may result from marked mesangial expansion and capillary occlusion. However, in this broad range of patients it appeared that global glomerular sclerosis and mesangial expansion were not infrequently independent diabetic renal lesions which could contribute separately to the ultimate development of overt diabetic nephropathy. PMID- 1921146 TI - Acanthocyturia--a characteristic marker for glomerular bleeding. AB - Erythrocyte morphology by phase contrast microscopic examination (PCM) of the urine is widely employed in distinguishing glomerular from nonglomerular bleeding. The proposed percentages of dysmorphic red cells are significant for glomerular bleeding in the range of 10 to 80% in the literature, because there is no clear cut definition of "dysmorphism." In the present study midstream urine samples of 351 patients with hematuria (greater than 8 erythrocytes/microliters) and of 33 healthy controls were examined. The various dysmorphic red cells were analyzed by PCM according to a detailed hematological classification. Most of the dysmorphic red cells, such as echinocytes, anulocytes, ghost cells, schizocytes, stomatocytes, codocytes and knizocytes, occurred in glomerular or nonglomerular disease as well, and proved to be uncharacteristic for glomerular bleeding. In contrast, a unique red cell deformity, a ringform with vesicle-shaped protrusions (acanthocyte) closely correlated to glomerular disease. In biopsy proven glomerulonephritis acanthocytes comprised 12.4% of all excreted red cells, whereas in nonglomerular diseases or in healthy subjects acanthocytes were seen very rarely (less than 2%) or not at all. Acanthocyturia greater than or equal to 5% (of excreted red cells) was seen in 75 out of 143 patients with proven glomerulonephritis (sensitivity 52%) and in four out of 187 patients with nonglomerular disease (specificity 98%). To improve the diagnostic value of erythrocyte morphology the diagnostic workup should focus on acanthocyturia, which is also indicative in very low erythrocyte counts. PMID- 1921147 TI - Treatment with recombinant human erythropoietin increases antibody titers after hepatitis B vaccination in dialysis patients. AB - The effect of recombinant human erythropoietin (rHuEPO) on the immune system of hemodialysis patients has been studied by evaluating their response to hepatitis B (HB) vaccination. Fifty hemodialysis patients were given four doses of 20 micrograms recombinant DNA hepatitis B vaccine (SKF) at an interval of 0, 1, 2 and 6 months. Thirty-seven patients could be evaluated at one year. Twelve of 15 (80%) of the rHuEPO treated patients and 12 of 22 (54%) of non-rHuEPO treated dialysis patients developed anti-HBs antibodies. At the time of maximum immune response (8 months), the geometric mean anti-HBs titers (mIU/ml +/- SEM) of responders and all patients were five times (224.0 +/- 5.9 vs. 41.7 +/- 1.5, P less than 0.001), and eight times (57.6 +/- 8.7 vs. 6.7 +/- 1.8, P less than 0.05), respectively, higher in rHuEPO treated patients than in patients not receiving the drug. High antibody response (greater than 100 mIU/ml) prevailed in the group of rHuEPO treated patients and was associated with a high helper/suppressor ratio. Discriminant multivariate analysis (P = 0.038) revealed the influence of treatment with rHuEPO (40%) and helper/suppressor ratio (31%) on antibody concentration, while age, gender, duration of dialysis and previous blood transfusions were similar in both patient groups. Although changes in lymphocyte subsets observed in rHuEPO treated patients may be the result of a reduced administration of blood transfusions, immune reactivity seems also to be directly affected by the drug. PMID- 1921148 TI - Metabolism of apolipoprotein B-containing lipoproteins in subjects with nephrotic range proteinuria. AB - Although hyperlipidemia is a well recognized complication of the nephrotic syndrome, the precise disturbances of lipoprotein metabolism which cause the elevated plasma lipid and lipoprotein concentrations have not been clearly defined in humans. This study examines the metabolism of apolipoprotein B containing lipoproteins in patients with nephrotic-range proteinuria and in healthy controls. Two radioiodinated tracers of very low density lipoproteins (VLDL1, Sf60 to 400, and VLDL2, Sf20 to 60), were used to trace the metabolism of apolipoprotein B through the delipidation cascade from very low density lipoproteins (VLDL) to low density lipoproteins (LDL). The data from the apoB specific radioactivity curves and the pool sizes of apoB in four subfractions were analyzed by a multicompartmental modeling procedure using the SAAM 30 program. The main findings in the nephrotic group were: 1.) a consistent decrease in the fractional rate of apoB transfer from VLDL1----VLDL2 (median values nephrotic 0.92 pools/day vs. controls 3.66, P less than 0.02) and from VLDL2--- IDL (1.49 vs. 2.74, P less than 0.05); 2.) increased secretion of apoB into VLDL2 (14.5 mg/kg/day vs. 4.2, P less than 0.02); 3.) a trend towards decreased removal of IDL and LDL attributable to a defect in LDL receptor-mediated removal as previously shown (Metabolism 39:187-192, 1990). These findings suggest that catabolic defects of the apo B-containing lipoproteins are as important as increased hepatic synthesis in the pathogenesis of nephrotic hyperlipidemia in humans. PMID- 1921149 TI - Reversible compensatory hypertrophy in transplanted brown Norway rat kidneys. AB - Recently we described methods for optimizing the function of transplanted rat kidneys. In unilaterally nephrectomized recipients, one week after surgery, the left transplanted kidney was identical to the right native kidney with respect to wet weight and the clearances of inulin and para-aminohippuric acid (PAH). The goals of the present experiments were first, to extend the post-surgery period to three weeks (sufficient to allow hypertrophic changes), and second, to study function of transplanted hypertrophied kidneys. Genetically identical Brown Norway rats were used as donor and recipients. Three weeks after transplanting a normal kidney into a unilaterally-nephrectomized recipient, the transplanted kidney had a normal plasma flow and was identical to the contralateral native kidney with respect to wet weight and the clearances of inulin and PAH. Three weeks after transplanting a normal kidney into a bilaterally-nephrectomized recipient, the wet weight, inulin and PAH clearances, and plasma flow of the transplanted kidney were all higher than control, and not significantly different from those observed in unilaterally-nephrectomized control rats. Thus, transplanted and native kidneys exhibited the same degree of compensatory hypertrophy. Hypertrophied donor kidneys (that is, the donor rat had been unilaterally-nephrectomized three weeks previously) remained hypertrophied in bilaterally-nephrectomized recipients, but in unilaterally-nephrectomized recipients, they regressed towards normal (that is, the values of wet weight, inulin and PAH clearances and plasma flow were significantly less than those in rats with only one kidney) while the contralateral native kidney remained normal (values of wet weight and inulin and PAH clearances were not different from control).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921150 TI - Analysis of the cDNA sequence encoding MHC-A beta in tubular epithelium from mouse kidney. AB - Class II gene products of the major histocompatibility complex (MHC) are not expressed usually in abundance on normal epithelium. The cell surface visibility of such proteins for the immune system is thought to be limited protectively in order to minimize inflammation consequent to the recognition of self-antigens in parenchymal structures by T lymphocytes. In the current experiments we investigated whether the previously recognized sparseness of A beta on the surface of tubular epithelial cells might be accounted for by a protein coding difference deduced from the primary structure of its transcript compared with sequence from lymphoid cells that normally express A beta in generous amounts. We demonstrate, however, using clones obtained from a cDNA library prepared from tubular epithelium harvested from H-2s (A beta/alpha+; E beta/alpha-) mice susceptible to autoimmune interstitial nephritis, that the nucleotide sequence encoding the class II A beta chain in cells from both compartments is essentially identical. Our findings suggest that there is no primary structural aberrancy in the coding region of parenchymal A beta that would contribute to its low expression. The protective tolerance afforded by reduced numbers of class II molecules in normal tissues is, therefore, more likely the result of repressive regulatory processes. PMID- 1921151 TI - Acquired cystic kidney disease. PMID- 1921152 TI - Role of growth hormone in the development of experimental renal scarring. AB - Recent experimental data has implicated growth hormone in the development of glomerular sclerosis. In this study, we have examined the development and progression of glomerular and tubulointerstitial scarring in Wistar and Dwarf rats, selectively growth hormone-deficient, following subtotal nephrectomy. Wistar rats showed progressive proteinuria, hypertension and renal failure as well as severe renal scarring 120 days after subtotal nephrectomy. In contrast, growth hormone-deficient Dwarf rats had minimal proteinuria, mild renal functional impairment and moderate renal histological scarring. The difference in these functional and structural parameters between the two strains is highly significant, although both experimental groups had comparable food consumption and systemic blood pressure. The significantly smaller glomeruli and limited kidney hypertrophy over 120 days observed in Dwarf rats may account for some of the protection against glomerular sclerosis and tubulointerstitial scarring observed in that strain. PMID- 1921153 TI - Puromycin aminonucleoside metabolism by glomeruli and glomerular epithelial cells in vitro. AB - Two puromycin aminonucleoside (PAN) excretion products were purified by HPLC from urine of PAN-treated rats and characterized by nuclear magnetic resonance as N6 dimethyl-3'amino-3'deoxyadenosine (DA-Ado) and N6-methyl-3'amino-3'deoxyadenosine (MA-Ado), respectively, the former corresponding to unmodified PAN. DA-Ado was not a substrate for adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) or xanthine oxidase (XO), while MA-Ado was consecutively converted into hypoxanthine by a mixture of ADA and PNP. A different rate of transformation of DA-Ado and MA-Ado into hypoxanthine by isolated glomeruli was observed and was higher for the monomethylated analogue by a factor of 3 (79% vs. 21%); this was ascribed to the rate-limiting level of a demethylase activity acting on DA-Ado. Furthermore, DA-Ado was not transformed by glomerular epithelial cells in culture, while a little amount of MA-Ado was converted into hypoxanthine after six hours of incubation. In spite of this different metabolic behavior, the same order of cytotoxicity on glomerular epithelial cells in culture was observed for MA-Ado, DA-Ado and commercial PAN. All these molecules induced a dose response inhibition of [3H]thymidine incorporation into DNA after exposure for two hours and a marked alteration of cell viability which was not inhibited by free radical scavengers and deferoxamine. This study provides the first evidence for a glomerular metabolism of PAN and its urinary metabolite MA-Ado involving their transformation via the purine cycle enzymes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921154 TI - Antiserum against tumor necrosis factor-alpha and a protease inhibitor reduce immune glomerular injury. AB - Previous studies in this laboratory have documented tumor necrosis factor alpha (TNF) release by macrophage laden glomeruli in the accelerated autologous form of nephrotoxic serum nephritis (AA-NTSN). We now report that the administration of anti-TNF antiserum to rats with the AA-NTSN reduces albuminuria in a dose related manner (day 8 postinduction) and limits glomerular necrosis (P less than 0.05) without affecting the endogenous creatinine clearance (CCr). Protease inhibitors block cytolytic activity of TNF in vitro and reduce glomerular necrosis in experimental nephritis in vivo. The combined administration of anti-TNF antiserum and an amidine-type protease inhibitor (BABIM) to rats with the AA-NTSN caused a greater diminution of albuminuria and histopathology than observed in rats treated with either agent alone, and also prevented the fall in CCr otherwise observed in this model system. Since, in our studies, BABIM did not inhibit cytolytic TNF activity in vitro, we conclude that the effects of combined administration of these two agents are mediated by independent mechanisms. Our results highlight the pathogenic significance of local TNF release in immune renal disease accompanied by prominent glomerular macrophage accumulation. PMID- 1921155 TI - Expression of alpha B-crystallin in the developing rat kidney. AB - The expression and cellular localization of alpha B-crystallin during rat renal development was studied by Northern blot analysis and by immunocytochemistry. Northern blotting of total RNA extracted from whole kidneys revealed that the messenger RNA for alpha B-crystallin rapidly increased after birth to reach adult levels by 20 days. At the same time, immunohistochemistry for alpha B-crystallin demonstrated that the prominent elongation of Henle's loop during the first 10 days of life was accompanied by increased alpha B-crystallin expression. Thus, the development of alpha B-crystallin expression is correlated temporally with the acquisition of tubule function in early post-natal life. PMID- 1921156 TI - Acute and chronic changes in renal function following unilateral nephrectomy. AB - Free-flow micropuncture was used to assess proximal and distal tubular function in rats immediately (2 to 5 hours), five days and 30 days after uninephrectomy (UN); results were compared with those in sham-operated littermates. Excretion rates of water, sodium and potassium were approximately doubled in the remaining kidney of UN rats. Two to five hours after UN there were small increases in glomerular filtration rate (GFR) and single nephron GFR which at this stage were not accompanied by an increase in absolute proximal reabsorption; that is, fractional proximal reabsorption fell. After five days, GFR and single nephron GFR had increased further; at this stage absolute proximal reabsorption was also significantly elevated. After 30 days, kidney weight, GFR, single nephron GFR and absolute proximal reabsorption had all increased by approximately 40%, and glomerulotubular balance in the proximal tubule had been fully restored. Data derived from distal tubular collections indicated that at every stage after UN: (a) fluid delivery to both early and late distal puncture sites was increased; (b) in contrast, there was no increase in sodium delivery to the late distal tubule, suggesting that the natriuresis resulted from reduced sodium reabsorption beyond the distal tubule and/or increased delivery of sodium from deep nephrons; and (c) there was a marked increase in potassium secretion into the accessible portion of the distal tubule which was more than adequate to explain the observed kaliuresis. PMID- 1921157 TI - Organ distribution of erythropoietin messenger RNA in normal and uremic rats. AB - We used RNAase protection assays to measure low levels of erythropoietin messenger RNA (EPO mRNA) in the organs of unstimulated rats, and to compare basal and stimulated levels of EPO mRNA in the kidneys and extrarenal organs of rats rendered uremic by subtotal nephrectomy, with pair-fed controls. Using this sensitive assay, EPO mRNA was measured in the kidneys of unstimulated control animals and was detectable, at lower levels, in the liver and lung. After exposure to hypoxia, there was a 150-fold increase in renal EPO mRNA. Hepatic EPO mRNA was also greatly increased and accounted for 39 +/- 10% of the total. The small quantity of EPO mRNA in lung did not increase, but EPO mRNA became detectable in spleen. Animals subjected to subtotal nephrectomy became uremic and anemic (hematocrit 0.32 +/- 0.04 vs. 0.43 +/- 0.04 in controls, P = 0.002), but serum EPO concentrations were not significantly increased (32 +/- 9 vs. 24 +/- 6 mU/ml, P = 0.14). However, after hypoxic exposure, uremic animals increased serum EPO concentrations greatly, although the response was less than in controls (349 +/- 82 vs. 1009 +/- 238 mU/ml, P = 0.002). After hypoxia, extrarenal EPO mRNA levels in uremic animals were similar to controls. In particular, the large hepatic potential for EPO mRNA synthesis was unchanged but accounted for a greater proportion (84 +/- 5%) of the total EPO mRNA. The renal EPO mRNA content was reduced, as expected, after subtotal nephrectomy, but increased 50-fold after hypoxia. In this model of chronic renal failure, despite anemia, a large potential for EPO synthesis exists in liver and remnant kidney. PMID- 1921158 TI - Toxicity of peritoneal dialysis fluids on cultured fibroblasts, L-929. AB - Peritoneal dialysis (PD) fluids are known to suppress the reactions of inflammatory cells in vitro. PD-fluids have also been shown to have cytotoxic influence on mesothelial cells. The combinations of these factors may have a detrimental effect on the peritoneum or may impair cellular defence against bacterial peritonitis. Some authors have discussed the relevance of heat sterilization to both so-called peritoneal side-effects and to chemical decomposition of fluids. Four commercial PD-fluids and one laboratory-made PD fluid were tested for cytotoxicity on a cultured fibroblast cell line, L-929. Cytotoxicity was determined as an inhibition of cell growth by quantification of total protein. The laboratory-made PD-fluid was sterilized either by filtration or by filtration and heat. The commercial and the heat-sterilized laboratory made PD-fluids caused significant inhibition of cell growth (53 to 76%) in contrast to saline and the filter-sterilized laboratory-made PD-fluid. Since the pH values of all the testsolutions were neutral, low pH was not the cause of toxicity. Our results regarding the L-929 cells indicate that the cytotoxicity of PD-fluids is of a general nature. Furthermore, the results indicate that the heat sterilization process might be partially responsible for causing toxicity in PD fluids. PMID- 1921159 TI - Influence of antiidiotypic antibody activity on renal transplant outcome. AB - The presence of cytotoxic HLA antibodies (Ab1) against donor lymphocytes in pretransplant sera is almost always associated with rapid rejection of the renal transplant. We have investigated the possibility that antiidiotypic antibodies (Ab2) to cytotoxic HLA antibodies might modulate the immune response and favorably influence renal allograft outcome. The role of antibodies (Ab3) which potentiate the cytotoxic effect of Ab1 was also studied. Pretransplant sera from 63 patients were tested for inhibitory or potentiating activity in the short antiidiotypic assay. Inhibitory activity was detected in 30 patients and in 28 the transplant survived more than a year. Of patients without antibody activity 11 of 17 had grafts surviving more than one year, and of those showing potentiating activity 11 of 16 were functioning at a year. The difference in transplant survival between the first group and the other two groups was statistically significant (P less than 0.05). There was no significant difference in survival rates between the latter two groups. Potentiating activity is therefore not an independent predictor of transplant failure, whereas the presence of antiidiotypic antibody activity did correlate with improved allograft survival. PMID- 1921160 TI - Cytokine-activated human mesangial cells generate the neutrophil chemoattractant, interleukin 8. AB - Human mesangial cells (MC) in culture, when stimulated by interleukin 1 alpha(IL 1 alpha) or tumour necrosis factor (TNF alpha), but not with lipopolysaccharide (LPS), express interleukin 8 (IL-8) mRNA, and both cell associated and extracellular IL-8. Dexamethasone treatment of mesangial cells induced partial inhibition of the release of extracellular IL-8, while cell-associated IL-8 and IL-8 mRNA were not significantly altered. We propose that the mesangial cell has a direct role in the initiation and propagation of inflammatory events within the glomerulus via the generation of the chemotactic cytokine IL-8. PMID- 1921161 TI - Inhibition of immunoglobulin production by parathyroid hormone. Implications in chronic renal failure. AB - Available data indicate that B cell proliferation is inhibited in chronic renal failure and this is due to excess blood levels of PTH. This defect may also affect immunoglobulin production. We examined production of IgG, IgM and IgA by B cells stimulated with Staphylococcus aureus Cowan I (SAC) or with pokeweed mitogen (PWM) after eight days of culture and evaluated the effect of PTH on this process in 34 hemodialysis patients and 44 normal subjects. IgG, IgM and IgA production by B cells from patients was lower (P less than 0.01) than by B cells from normal subjects. Both 1-34 and 1-84 PTH inhibited (P less than 0.01) immunoglobulin production by B cells from normal subjects and dialysis patients. However, this inhibitory effect was evident in dialysis patients only with the higher dose of PTH. The inhibition of immunoglobulin production by PTH occurred only when the hormone was added at the initiation of the B cell culture. Inactivation of PTH abolished its inhibitory effect on immunoglobulin production. Agents that stimulate cAMP production (forskolin, cholera toxin) and the cAMP analogue, 8-bromoadenosine 3',5' cyclic monophosphate inhibited immunoglobulin production by B cells from both normal and dialysis patients, and the degree of inhibition was not different between the two groups. The calcium inophore A23187 also inhibited IgG, IgA and IgM production by B cells from normal subjects and dialysis patients; there was no significant difference in the degree of inhibition between the two groups. The resting levels of cytosolic calcium in B cells of dialysis patients was significantly (P less than 0.01) higher than that of B cells from normal subjects. The data show that: (1) immunoglobulin production is impaired in dialysis patients; (2) B cells of dialysis patients have elevated resting levels of cytosolic calcium; (3) PTH inhibits IgG, IgA and IgM production and this effect is at least partly mediated by PTH-induced cAMP production and alterations in cytosolic calcium into B cells; (4) this inhibitory effect is mediated by events that affect initial stages of B cell proliferation and maturation; (5) the requirement for high dose of PTH for its inhibitory effect on B cells from dialysis patients is probably due to desensitization and/or down-regulation of PTH receptors on B cells. The results are consistent with the proposition that impaired immunoglobulin production by B cells from dialysis patients is at least partly due to the state of secondary hyperparathyroidism in these patients. PMID- 1921162 TI - [The polymerase chain reaction PCR and its use in genetic diagnosis]. AB - In genomic diagnosis the ensemble of techniques has been recently expanded by the powerful method of the polymerase chain reaction (PCR). Using pairs of synthetic oligonucleotides for priming of synthesis and a thermoresistant DNA polymerase a millionfold amplification of target DNA sequences from patients provides DNA fragments for following investigations such as electrophoresis. The paper presents some examples of PCR application for diagnosis in cystic fibrosis and Duchenne muscular dystrophy. PMID- 1921163 TI - [Value of bronchography in childhood with special reference to nuclear medicine preliminary examinations]. AB - One month to 16 years old 288 children suffering from recurrent and chronic bronchitis, asthma, cystic fibrosis, malformations and various other lung diseases have been undergone 133Xe-Gas/99mTc-HAM lung scintigraphy. By means of results and taking in consideration scintigraphic findings the strategy of bronchographic indication is laid open being of higher load for the children based on anaesthesia and x-ray. Thus the number of bronchographs could be reduced from 47 (1984) via 33 (1985) to 22 (1986) by means of lung-scintigraphic imaging. PMID- 1921164 TI - [The significance of the flow-volume curve in pediatric lung diseases]. AB - Even slight obstructions in small airways are detectable by means of the flow volume curve. Therefore this method is to recommend for early diagnosis and especially in infancy. Advantages were demonstrable at the examination of different groups of asthmatics and in children with cystic fibrosis. The great sensitivity of the flow values was also shown at the bronchospasmolytic test and for provocation tests particularly. The flow-volume curve is an important routine method in pediatric pulmonology to determine the dimension and location of ventilation disorders and for follow-up studies and therapy supervision. PMID- 1921165 TI - [Parameters of mineral metabolism in children and adolescents in athletic training]. AB - Changes in bone structure like chondronecrosis and osteonecrosis occurred in a group of adolescent athletes especially gymnasts. To determine the etiology calcium, inorganic phosphorus, alkaline phosphatase activity and levels of 25-OH Vit D were investigated. Single low calcium values were present in nearly the half of the athletes. In 37% the vitamin-D-levels were depressed. Such results were found in athletes with and without changes in bone structure. A vitamin D supplementation is recommended if low vitamin D levels are found. Vitamin D deficiency is not the only reason for the disturbances of the bone. Other factors are to take in consideration like nutrition, delayed bone maturation and its consequences, and the mechanical load. PMID- 1921166 TI - [Hemorrhagic colitis and hemolytic-uremic syndrome--E. coli as the etiologic agent. I. Bacteriology and pathogenesis]. AB - Since 1983 when the connection between haemorrhagic colitis (HC), haemolytic uraemic syndrome (HUS), and intestinal infections by verotoxin-producing E. coli (VTEC, EHEC) was demonstrated, a lot of arguments has been accumulated showing verotoxins (Shiga-like toxins, SLT) and adhesive fimbria to play a key role in the pathogenicity of the respective E. coli group. The toxins bind via Gb3 receptors to the target cells and after internalization inhibit the protein synthesis. Due to the particular clustering of receptors at cell surfaces, vascular endothelial cells, intestinal epithelial cells as well as kidney and nerve tissues are especially affected. The severity of illness is obviously dependent on the relation between release of toxins and the actual level of anti toxin-IgG in the blood. PMID- 1921167 TI - [Reye syndrome]. AB - A survey about the Reye-syndrome including diagnosis, symptoms, therapy, and differential diagnosis is actually presented. The related problems of its pathogenesis, etiology and epidemiology are discussed. It is recommended to diagnosis this disease for registrating its frequency and distribution on the area of Germany. PMID- 1921168 TI - [How frequently and with what symptoms are children presented to the pediatrician?]. AB - Author prepared and processed 1500 computerised questionnaires in which primary school children parents were asked about their knowledge of symptoms of childrendisease and habits: "how to consult with physicians". The questionnaire was divided 3 parts: in the first one general questions and some problem in connection with high-temperature, in the second one about symptoms, and in the third group pains were mentioned located in organs and different body-parts of children. The majority of parents accepted these questions and gave good answers and prepared some additional suggestions. Other group of parents having very bad habits relation to symptoms, and "how to consult with doctors and call duty system". Author emphasized the very important role of data processing system for the further health organisation and health education. PMID- 1921169 TI - [Current recommendations for infant nutrition, especially for the new concept of soft food]. PMID- 1921170 TI - [Hemorrhagic colitis and hemolytic-uremic syndrome--E. coli as etiological agent. II. Clinical aspects and epidemiology]. AB - In the last few years a group of verotoxinogenic E. coli bacteria has been defined as a causative agent of hemorrhagic colitis and haemolytic uremic syndrome. The corresponding toxins (verotoxins, Shiga-like-toxins) released from these bacteria play a key role in the pathogenesis and are responsible for the severity of the respective illness. Therefore, besides the clinical and other paraclinical investigations the detection of SLT-producing E. coli or of the corresponding toxins directly in the stool as early as possible has to be included into strategies for diagnostics and therapy. Moreover, it is necessary to avoid the release of huge amounts of toxins (e.g. by antibiotic therapy) and to take care for suitable measures to neutralize or eliminate the toxins. First isolations of enterohaemorrhagic E. coli (EHEC, VTEC) in stool samples from patients suffering from diarrhoeal diseases and HUS in the vicinity of Wernigerode demonstrate the necessity for further bacteriological and epidemiological investigations in order to evaluate frequency and importance of these EHEC bacteria in the pediatric praxis. PMID- 1921171 TI - [Results of specific hyposensitization in children with pollinosis]. AB - Hyposensitization was carried out in 120 children aged 5 to 15 years with proven sensitivity to various pollen for 3 to 5 years before the start of the season. By reason of the results of intracutaneous tests 90 patients were treated with mixed pollen allergen and 30 patients with grass pollen allergen. A retrospective study was undertaken on the base of a questionnaire. Every year after the season duration and severity of symptoms as well as consumption of medicine were registered. The total success of hyposensitization amounted to 70.8% and this result varied on the one hand in dependence of the duration of disease on the other hand in dependence of the duration of treatment. A more inconvenient result was seen in those children who suffered from asthmatic symptoms exclusively compared to patients with hay fever. Local side effects resulted sporadically in 71.5% and systemic side effects in 15.7% by subcutaneous injection of depot pollen allergen. Despite of extensive and not indifferent mode of treatment, hyposensitization should be performed in a correct way as soon as possible after exact indication. PMID- 1921173 TI - [Blow-out fractures in childhood]. AB - Both of large groups, lateral and central facial skull fractures, are further divided into isolated fractures of particular localisation (zygomatic arc, orbital floor fractures etc.) and compound fractures of varying degrees. 33 patients aged 5 to 14 years with fractures of the orbital floor (blow-out fractures) were followed up for 3 months to 9 years. Advances in the primary surgery have contributed to an improvement in the treatment of defects. The present investigation confirms the view that blow-out fractures with diplopia and prolaps in childhood require early surgical treatment. PMID- 1921172 TI - [Intracranial hemorrhage in preterm- and full-term newborn infants. Frequency and prognosis for development]. AB - In a prospective study 306 high-risk infants with a birth-weight between 890 to 4900 gm were examined by means of cerebral ultrasound scanning and about a time of two years the psychomotor development was evaluated. 145 patients (47.4%) were classified as intracerebral haemorrhages. The strongest relation with the event of bleeding was found for the high level of PCO2. With increased severity of the intracranial haemorrhage was associated a worse prognosis of development in the first two years of life. The type I-haemorrhage showed in 72.2%, the types III/IV in yet only 42.9% a development without psychomotor disorders. PMID- 1921175 TI - [Follow-up of development following inflammatory CNS diseases in childhood]. AB - In the acute phase of inflammatory diseases of the CNS diagnosis and outset of treatment should be effected with the least possible delay to that avoiding risks of partial recovery. The regained quality of life is of increasing importance for the evaluation of intensive and supportive therapy as mortality could be markedly decreased by anti-bacterial and antiviral treatment. Only a close follow-up will result in definite prognostic assertions. For the early detection of secondary damages the complete battery of up-to-date neurologic diagnostics has to be considered. PMID- 1921174 TI - [Determination of secretory immunoglobulin A in the saliva of children with recurrent and chronic respiratory tract diseases during a stay at a health resort]. AB - Investigations of sIgA-concentrations in saliva of 101 children in age of 2 to 4 years with recurrent and chronic airways diseases were performed by means of a sIgA specific enzyme linked immunoassay. The aim was to find out immunodeficiencies in comparison to healthy children (n = 50), and to test whether or not there is an influence of medical and climate treatment over a period of 8 weeks onto sIgA values in saliva. Only 3 children showed decreased sIgA concentrations. There were no differences between patients and healthy children because of the great interindividual variances of sIgA concentrations. An effect of climate cure to sIgA values could not be shown. PMID- 1921176 TI - [Etiological, clinical and roentgenological aspects of mediastinal emphysema in children and adolescents]. AB - The authors publish 8 cases of emphysema of the mediastinum in childhood and adolescence. The aetiologic variety and the radiologic symptoms are presented. Chronic diseases of the lungs and the respiratory tract, injuries of the thorax or iatrogenic genesis are the cause of emphysema. The spontaneous emphysema of the mediastinum is rare in childhood and adolescence. PMID- 1921177 TI - [Acrocephalosyndactylia with multiple exostoses, bilateral parieto-occipital "encephaloceles", micropenis and severe mental retardation]. PMID- 1921179 TI - [An open letter to the journal "Khirurgiia"]. PMID- 1921178 TI - [Early history of pediatrics in Mecklenburg. 3: Health resorts for children]. AB - The groundwork for spa facilities intended for the treatment of children was performed by Dr. Carl von Mettenheimer in Schwerin with the foundation of a "Verein fur die Errichtung von Kinderheilstatten an deutschen Seekusten" ("Association for the Establishment of Pediatric Sanatoria on German Coasts"). The contribution describes the construction and development of the first sanatorium for children at Murtiz on the Baltic coast. Attention is also drawn to the establishment, development and importance of the children's sanatorium "Bethesda" at Sulze. The importance of the role played by the hygiene specialist Prof. Uffelmann (Rostock) and the pediatricians Dr. Carl von Mettenheimer (Schwerin) and Prof. Herrmann Bruning (Rostock) in the development of child care and pediatrics even beyond the borders of Mecklenburg cannot be overestimated. PMID- 1921180 TI - [Means of preventing suppurative complications following surgery of the liver]. AB - The article analyses the results of antibiotic prevention of postoperative infectious complications and the use of special techniques and operative manipulations in 60 patients with localized affections of the liver. It was found that the most effective method of antibiotic prevention of complications is a purposeful transport of antibiotics in autologous erythrocytic shadows, which are infused intravenously once before the operation and, in extensive resection of the liver, on the second or third postoperative day. With the use of special techniques and operative manipulations in combination with purposeful transport of antibiotics the frequency of infectious complications reduces and the results of treatment in surgery of localized affections of the liver improve. PMID- 1921181 TI - [Oblique-angled incision of the skin]. AB - The results of using an obliquely-splitting incision of the skin in 105 patients were studied. A good cosmetic effect without the formation of a coarse scar elevated above the skin surface was produced in all of them. It was achieved due to preservation of the tissue trophics. The skin is cut at an angle of 15 degrees to the skin surface in the region of the operation, as a result of which angular splitting of the epidermis 1.2-1.5 cm wide is formed. At the end of the operation the flaps are apposed tile-like and sutured with buried interrupted or removable mattress sutures. PMID- 1921182 TI - [Reconstruction of the elbow joint in a replanted upper extremity using the microsurgical autotransplantation method]. AB - Described is the method of the elbow joint reconstruction by means of free microsurgical autotransplantation of the vascularized Ist metatarsophalangeal joint. The technique has been tested in the clinic and a good functional result was obtained in a patient who had undergone emergency resection of the elbow joint in replantation of the upper limb. The authors believe that introduction of such operations in the clinical practice would significantly broaden the range of indications to replantation of the upper limb amputated at the level of the elbow joint. PMID- 1921183 TI - [Sorption lavage of suppurative wounds]. PMID- 1921185 TI - [Suppurative arthritis caused by Salmonella]. PMID- 1921184 TI - [Localization of dirofilariasis in humans]. PMID- 1921186 TI - [A foreign body causing emphysema of the pararectal tissue]. PMID- 1921187 TI - [Current aspects of transplantation of the pancreas]. PMID- 1921188 TI - [Prophylactic use of antibiotics in the clinical picture of general surgery]. PMID- 1921189 TI - [Preoperative determination of the boundaries of soft tissue necrosis in patients with diabetes mellitus]. AB - The authors examined 34 patients with diabetes mellitus and purulent diseases of the soft tissues and 40 persons who formed the control group. The study of local microcirculation in the purulent focus, in a purulent and closed wound by determining the oxygen tension in capillary blood (pO2) established by using an noninvasive method that a real possibility for determining the exact boundaries of tissue necrosis has appeared. This makes it possible to excise optimally the necrotic tissues and choose the techniques of applying primary, primary-delayed or early secondary sutures. In addition, the study of the dynamics of pO2 changes allows the course of the wound process to be followed up and, consequently, possible suppuration of the wound to be predicted. PMID- 1921190 TI - [The use of lasers in surgery of the liver]. PMID- 1921191 TI - [The effect of the physical factors of treatment on lipid peroxidation in surgical infections in patients with diabetes mellitus]. AB - Lipid peroxidation was studied in 179 patients with purulent surgical diseases and diabetes mellitus. Magnetotherapy, laser radiation, low-frequency ultrasound, ultraviolet irradiation of blood, and sorbent application were used as therapeutic factors. It was found that laser and ultraviolet irradiation of blood, and application of sorbents to the purulent wounds promoted stabilization of lipid peroxidation, had a more marked effect on the course of the wound process, and reduced the term of treatment. PMID- 1921192 TI - [Wound healing as affected by constitutional immunity factors]. AB - The authors examined 52 patients with gunshot wounds of various localization. Besides the type of wound healing, they determined the ABO system blood groups, the value of phagocytosis intensity and the value of connective tissue saturation with ascorbic acid, which, as it was shown earlier, are unrelated to the current condition of the wound process and may serve for predicting the risk of wound purulent complications. The distribution features of the studied values in patients with gunshot wounds were compared with those in individuals with gunshot inflicted wounds. It is shown that such signs of constitutional immunity as the B blood group, weak phagocytosis intensity, and low saturation of the connective tissue with ascorbic acid are risk factors of purulent complications in both traumatic and gunshot wounds. PMID- 1921195 TI - [The open method of surgical treatment of suppurative wounds]. AB - Treatment of purulent wounds by the open method in 280 patients was analysed. It is shown that purposeful use of medicinal agents in accordance with the phases of the wound process is a determinant and influences the duration of treatment. Necrectomy in combination with the topical use of ointments on a water-soluble polyethylene glycol basis (levosin, levomekol, 5% dioxidine ointment, 10% mafenide acetate ointment) produces the most favorable effect on the course of the wound process. PMID- 1921194 TI - [Kidney and pancreas transplantation in patients with insulin-dependent diabetes mellitus]. AB - The article analyses the results of one-stage transplantation of the kidney and pancreas in three patients suffering from insulin-dependent diabetes mellitus with diabetic nephropathy in the stage of terminal renal failure which called for programmed hemodialysis. The specific features of early postoperative management of patients are described, particularly the various routes of drug administration. PMID- 1921193 TI - [Immunomodulating therapy of a suppurative infection of the soft tissues]. AB - The initial immunological status in patients with purulent infection of the soft tissues is characterized by T-cell deficiency and relative hyperfunction of the B immunity. The risk group with Grade 2-3T-cell immune deficiency takes up 44.5 77.5% and is encountered in patients with the B blood group and positive Rh factor in 79.1 +/- 5.2 and 70.8 +/- 4.3% of cases, respectively. Combination of sodium nucleinate and autohemotransfusion with the traditional therapy raises its efficacy. This is attended by correction of immunological disorders in T-cells and phagocytes, facilitates cleansing of the foci and increase of antibiotic sensitivity of the flora, and shortens the term of treatment. PMID- 1921196 TI - [Stimulation of the healing of aseptic wounds using laser irradiation]. AB - On the basis of experimental studies conducted on 535 albino Wistar rats and clinical observations over 125 patients, and from complex appraisal of morphological, biochemical, and tensiometric data the conclusion is drawn that optimal operative cutting of tissues is achieved by means of far infrared carbon dioxide laser beam with a wavelength of 10.6 microns. Comparison of these characteristics showed the strength of the postoperative scar to be much less in intraoperative tissue cutting with a steel scalpel or high-energy beam of an AIG laser with a wavelength of 1.06 microns. Low-intensity laser radiation increased the strength of the postoperative scar in the early periods in all groups. Tissue cutting with a high-energy carbon dioxide laser beam with a wavelength of 10.6 microns in combination with pre- and postoperative exposure of the zone of the incision to low-intensity 0.89 micron wavelength laser beam considerably increases the strength of the postoperative scar and is the method of choice in the treatment of aseptic wounds. PMID- 1921197 TI - [The rapid diagnosis of the anaerobic component of mixed infections in surgery]. AB - Rapid diagnosis of obligate anaerobes was conducted by means of gas liquid chromatography, bacterioscopy, and monitoring. It was found that in 80% of patients the results of rapid diagnosis coincided with those of complete cultural study. Monitoring of obligate anaerobes yields generalized information on their species composition, drug sensitivity, and etiological importance in mixed anaerobo-aerobic infections. The data of rapid diagnosis makes it possible to use directed antibiotic therapy before bacteriological examination is completed. PMID- 1921198 TI - [Prolonged local enzyme therapy of suppurative wounds]. AB - The article analyses the results of treatment of 150 patients with purulent diseases of the soft tissues of various localization, in which after surgical treatment the purulent focus immobilized trypsin (50 patients), trypsin with lysozyme immobilized on gauze (50 patients), and antiseptics (50 patients) were used for topical treatment of the formed wounds. The results of the treatment showed that topical prolonged enzyme therapy of purulent wounds with the use of trypsin immobilized on gauze and that with lysozyme promotes cleansing of the wounds, reduces microbial dissemination, intensifies reparative processes, and reduces the terms of treatment. PMID- 1921199 TI - [Modern detoxication methods in surgical patients]. AB - The therapeutic possibilities of peritoneal dialysis, hemodialysis, and hemo- and lymphosorption in the treatment of the intoxication syndrome were studied in 786 patients. The causes of the intoxication syndrome were as follows: postoperative peritonitis (98), acute renal insufficiency of various etiology (493), acute hepatorenal insufficiency with exogenous poisoning (178), diffuse purulent peritonitis (11), pancreatogenic peritonitis (6). Enzymatic lavage and peritoneal dialysis were applied in 98 patients, hemodialysis methods in 493, hemosorption was conducted 360 times in 178 patients and lymphosorption in 17 patients. The efficacy of the modern methods of detoxification of the organism was demonstrated, which was evaluated from the patients' improved general condition, improvement of the values of hemodynamics, concentration of toxic metabolites and middle-mass molecules in the blood, and the results of the paramecium test. PMID- 1921200 TI - [A comparative evaluation of hyper- and normovolemic hemodilution in the complex treatment of chronic hematogenic osteomyelitis]. AB - The article deals with the comparative analysis of the results of treatment of 98 patients with chronic hematogenic osteomyelitis of the long tubular and pelvic bones with the use of hypervolemic and normovolemic hemodilution as a method of infusion-transfusion therapy of intraoperative blood loss and its compensation with donor blood. It is shown on the basis of clinical evaluation and the study of hemodynamic, hematological, and rheological blood values, the values of the blood coagulation system and the acid-base balance that the use of hypervolemic hemodilution is limited and can be applied in blood loss not exceeding 10% of the circulation volume. The use of the method of normovolemic hemodilution makes the transfusion of donor blood unnecessary and thus allows the complications associated with it, infectious among others, to be avoided. It can be used in blood loss of up to 20% of the circulation volume. PMID- 1921201 TI - [Freezing an acutely necrotized extremity for the purpose of preparing the patient for amputation]. AB - 102 patients of a high operative risk were prepared for amputation of a lower extremity with acute ischemic gangrene by its freezing and tourniquet application. A special portable freezing chamber was used in most cases which could be installed in any surgical hospital. The refrigeration ranged from 18 hours to 14 days. Purposeful intensive treatment of all disorders suffered by the patient was conducted at the same time. In 92 patients the condition improved and the extremity was amputated. As compared to the control group, the postoperative mortality due to refrigeration reduced from 41 to 18.4%. The method was found to be highly effective in cases with gangrene and diabetes mellitus. PMID- 1921202 TI - [The surgical treatment of postburn cicatricial contractures of the knee joint extensors]. AB - In the recent 3 years operations were carried out in 8 patients with postburn extension contractures of the knee joints, which accounted for 12.9% of all cicatricial contractures of this joint. The anatomical essence of the contracture was ascertained. A method of surgical treatment was developed, which consisted in restoration of the cutaneoadipose layer in the region of the knee with a cutaneofascial graft taken from the contralateral leg and subsequent excision of the scars on the thigh, by freeing of the muscles extending the joint, and restoration of the skin surface with a split nonperforated autodermal graft. The operation restores knee joint movement and removes trophic ulcers of pathological postburn scars. PMID- 1921203 TI - [A method of preparing an arteriovenous shunt for chronic hemodialysis]. AB - The authors discuss their experience in forming arteriovenous fistulas for conducting chronic hemodialysis in 361 patients with accentuation placed on the features of performing repeated and multiple operations. The formation of arteriovenous fistulas in the lower third of the upper arm or the cubital fossa with retrograde blood flow into the venous system is the operal vessels, and a history of multiple operations on the forearm vessels. Hemodialysis in such cases should be started no sooner than two weeks after the operation. PMID- 1921204 TI - [The use of ultraviolet-irradiated plasma in the treatment of peritonitis]. AB - Intravenous infusion of the one-group lyophilized donor plasma irradiated with ultraviolet rays was included in the complex treatment of 43 patients with acute purulent peritonitis. The species-specific composition of the microflora was studied in the different groups of patients according to the cause of peritonitis and the degree of microbial contamination of the purulent wounds in patients treated with and without ultraviolet plasma irradiation (UVPI). For prognosticating the course and outcome of the disease the authors used a complex of indices linked with the manifestation of neutrophil bactericidal activity and the level of exogenous intoxication. A positive effect of UVPI in the management of acute purulent appendicitis was noted, which was confirmed by clinical and microbiological tests. PMID- 1921205 TI - [Blood reinfusion in acute blood loss during urologic surgery]. AB - In massive blood loss (1,000-4,900 ml) during operations on the kidneys and prostate in 42 patients, 900 to 3,600 ml of blood was reinfused. Thirty-seven (88.1%) patients recovered. Fatal outcomes in 5 cases were caused by complications of the principal and concomitant diseases and were unrelated to blood reinfusion. Study of the morphological, biochemical, and coagulation properties of the patients' blood showed gradual restoration of hemostatic values and no harmful effect of the reinfusion on the organism. The authors claim that blood reinfusion can be undertaken in operations on the kidneys and prostate when there are vital indications. Kidney tumors are a relative contraindication for reinfusion. Blood reinfusion is not indicated in purulent diseases of the kidneys. PMID- 1921206 TI - [The use of the laser scalpel in surgery of the spleen]. AB - The CO2 laser was used to arrest bleeding from traumatic wounds of the spleen in 24 patients. The success of laser coagulation was determined by the qualification of the surgeon who performed the operation and his skill in working with a laser scalpel. Comparative analysis of the intraoperative aspects and operative outcomes with those in 60 patients who underwent splenectomy (57) and suturation (3) showed the marked advantages of laser coagulation which allowed the spleen to be preserved in 63% of cases. PMID- 1921207 TI - [Characteristics of the early postoperative period following kidney allotransplantation and immunosuppression using Sandimmune (cyclosporin A)]. AB - The authors analysed the early postoperative period in 100 patients who received sandimmune (cyclosporine A) as the main immunosuppressant after kidney allotransplantation and compared it to that in a control group of 60 patients treated by the usual measures of immunosuppression: azathioprine and steroids. The number of rejection crises was 1.9 times less in the group of patients given sandimmune than in the control group and were more benign in character, while the number of irreversible crises reduced from 26% to 6%. In treatment with sandimmune the dose of oral prednisolone was reduced by 1.9 times and the dose of intravenous methypred by 1.4 times. Nephrotoxicity was the main side effect of sandimmune, it was encountered in 26% of patients. All sandimmune side effects are reversible in decreasing the dose. Sandimmune improves the results of kidney transplantation significantly. PMID- 1921208 TI - [The diagnosis and surgical treatment of nodular euthyroid and toxic goiter]. AB - The authors discuss their experience in treating 815 patients who underwent an operation for nodular euthyroid and toxic goiter. Thermography was used in the examination of 367 patients and the results were compared with those of radioisotope scanning of the thyroid, intraoperative findings, and the results of histological study. It was established that in complex with clinical methods of examination, thermography is very important in making the differential diagnosis of thyroid diseases. The specific features of surgical tactics in patients with nodular goiter are shown. Economical resection of the gland together with the node is recommended in nodular euthyroid goiter and subtotal subfascial resection of the involved lobe or the thyroid gland in nodular toxic goiter. PMID- 1921209 TI - [Intraoperative computed EEG monitoring for evaluating the adequacy of general anesthesia]. AB - The article analyses the possibilities of computed EEG monitoring for evaluation of the magnitude and adequacy of the modern methods of general anesthesia: NLA, NLA with halothane inhalation, NLA including Kalipsol bolus administration. An original coefficient, called the adequacy index (AI), was found, which reflects the percentage contribution of deep rhythms (delta and theta) to the total power of the EEG in the range of 0 to 20 Hz. It is shown that the dynamics of this index correlates with the degree of the blocking of entry of sensory nociceptive information into the CNS. The lower boundary of AI-70% was determined, below which the generally accepted signs of anesthesia inadequacy appear: hyperactivity develops, a shift of pH in the acid direction occurs, and the base deficiency increases. It is suggested that determination of AI is used as a highly sensitive and operative test for routine monitoring of the patient's intraoperative condition and express diagnosis of inefficacy of anesthesia. PMID- 1921210 TI - [Urachal cysts]. AB - The work analyses observation findings in three patients with urachal cysts. On admission, two of the patients had suppurating cysts simulating the picture of the acute abdomen, one of which presented the clinical signs of acute appendicitis so vividly as to require revision of the abdominal organs. The diagnostic errors that have been made are also analysed. A conclusion is derived by the authors on the expediency of an active surgical tactics in cases of suppurating urachal cysts. They suggest extensive cyst excision with application of continuous suture and drainage of the wound to be the operation of choice. PMID- 1921211 TI - [The surgical treatment of acute cholecystitis in patients in a group at increased risk]. AB - The article deals with the results of treatment of acute cholecystitis in 190 patients of the increased risk group. An urgent operation was performed on 25 patients, the others received intensive nonoperative treatment and were subjected to complex examination aimed primarily at assessing the hepatic function (ultrasonic examination with photometric determination of screen luminescent brightness, intraduodenal contact electrothermometry, plasma biochemical tests). In failure of this treatment 88 patients underwent transhepatic microcholecystomy, one-stage external-internal drainage was carried out in 43 patients. Operation was undertaken in the cold period in 104 patients; chloroform with procaine hydrochloride was administered through a catheter in 15 patients to dissolve gallstones. PMID- 1921212 TI - [Experimental studies of using polyester-coated materials of Polish production in surgical treatment of retinal detachment]. AB - The authors evaluated the tolerance of the rabbit eye to a new generation of polyester bands coated by polymethane polyester or by silicone. Investigations consisted on the application of episcleral implants made from polyester coated bands and--for comparison--of already well known polyester non-coated bands The eyes were removed on the 4th, 10th, 30th, 60th and 90th day after operation, macroscopically evaluated and fixed in formaline. The specimen were prepared from the spot of the applied implant together with a margin of surrounding tissues. Clinical observations, macroscopic evaluations as well as histopathological examinations showed a good tolerance of the silicone coated bands; it was discovered instead that the polyurethane coated bands are causing a more pronounced inflammatory reaction in the early postoperative period. PMID- 1921213 TI - [Experimental studies of using highly fluorinated alkane in the surgical treatment of retinal detachment]. AB - Fluids which are heavier than the vitreous fluid find recently their application in retinal detachment surgery. They fall down to the bottom of the eye and exerted pressure on the retina. Experimental investigations have been carried out on the possibility of application of these highly fluorinated alkane for operation. It has been demonstrated that this compound was very well tolerated by the tissues. It did not provoke any inflammatory or toxic reaction and did not cause any opacification of the optic media. On the spot of adherence it filtered in small quantities to the internal retinal layers. It could find probably its application in ophthalmic surgery. PMID- 1921214 TI - [Experimental studies of the role of the adrenergic system in the development of bioelectric response of the retina and visual cortex. II. Methodology and characteristics of the ERG and VEP recording]. AB - The author presents the method of performing computerized electroretinographic and visual evoked potentials in rabbits. Detailed characteristics of normal ERG and VEP records are presented. Discussed is the structure of the retina and of the visual pathways in the rabbit as well as the provenance of the particular peaks of the electroretinogram and visual evoked potential records. PMID- 1921216 TI - [Difficulties and errors in the diagnosis of retinoblastoma]. AB - The authors analyzed the results of the clinical and histopathological examination of the eyes of 283 children with an initially diagnosed intraocular tumor. In 32 cases (11.4 p.c.) there was no retinoblastoma but a congenital retinal dysplasia, vitreal dysplasia, Leber-Coats disease, chronic inflammatory conditions, or retinopathy of prematurity. Three eyes exhibited rare forms of intraocular tumors. In 4 cases among 283 (1.4 p.c.) the diagnosis was erroneously negative. One suspected the Leber-Coats, Hippel-Lindau disease or posterior uveitis. The pathological examination revealed the presence of retinoblastoma. PMID- 1921215 TI - [Experimental studies of the role of the adrenergic system in the development of bioelectric response of the retina and visual cortex. III. Effect of adrenaline on the ERG and VEP in rabbits]. AB - The influence of adrenalin on the electroretinogram and visual evoked potentials in rabbit were checked. After application of adrenalin the ERG showed a flattening of the a-wave and an increase of the b-wave amplitude and of oscillating potentials. One observed also a reduction of the A and B peaks and an increase of the C-wave in visual evoked potentials. On the basis of the results obtained the author discusses the role of the adrenergic system in the formation of the bioelectric response of the retina and visual cortex. PMID- 1921217 TI - [Retinal function after malignant hypertension in patients with transplanted kidneys]. AB - Ophthalmological examinations were carried out in 42 patients (aged 16-45 years) after kidney transplantation in whom malignant hypertension was discovered before transplantation. The first funduscopy revealed pathological changes of various type and grade (I-IV), in 17 patients the visual acuity was lowered and in 18 the ERG record was pathological (residual or extinguished). The control examinations performed in 19 patients after 1-5 years showed that the changes typical for malignant hypertension receded in 7; the fundus of the rest of the patients was the same as before. The lack of improvement in the ERG record points to a permanent lesion of the retinal activity after passed malignant hypertension in spite of normalization of the arterial pressure. PMID- 1921218 TI - [Vitreal and retinal changes in the fellow eye in children and adolescents with retinal detachment]. AB - The authors examined 78 fellow eyes in patients aged 2.5-20 years treated for retinal detachment. The examinations were carried out in the course of the hospital treatment and 2-10 years after the discharge from the Ophthalmological Department. In the period of observation the progression of the vitreous changes was seen in 9 eyes and it took the form of appearance or increase of the fibrillar degeneration of the vitreous, the condensation of its basis and of vitreoretinal adhesions; it coexisted with the appearance of new pathological processes in the retina. During the hospital treatment the retinal pathological changes were seen in 30.8 p.c. of cases and in the late examinations in 41 p.c. The most frequently discovered degeneration was the lattice degeneration. The frequency of the fellow eye syndrome in the late examinations increased from 10.2 p.c. to 17.7 p.c. of the examined patients. PMID- 1921219 TI - [Clinical studies of the tilted disc syndrome]. AB - Frequency of occurrence of all clinical signs in the tilted disc syndrome was studied in the paper because of variability of clinical picture in this syndrome. The most frequently occurring signs were: tilting of the disc (89%), oblique direction of the vessels (89%) and myopic astigmatism (96%). Other signs were observed less frequently: hypoplastic changes of retina and choroid in 82%, congenital conus in 45% and defects in the visual field in 55%. All sign of the syndrome were seen in 45% od the examined eyes. The most important signs of the syndrome are: tilting of the disc, oblique direction of the vessels and congenital conus. PMID- 1921220 TI - [Pupillometry in unilateral retinal detachment]. AB - The pupillary diameter was checked in illumination of various intensity in 20 patients with unilateral retinal detachment. The healthy and the diseased eye were examined separately. The authors discovered a latent anisocoria the amount of which was dependent on the condition of the macular area and on the extent of the detachment. PMID- 1921221 TI - [Retinal detachment of unknown etiology]. AB - Cases of retinal detachment of undetermined aetiology were analyzed on the material of the Ophthalmological Department in Wroclaw. Presented were the results of the surgical procedures taking into account the actual classification of the detachments. A positive anatomical result of the operation was achieved in 80 p.c. of patients, instead the improvement of the visual function was observed in only 56.5 p.c. of cases. PMID- 1921222 TI - [Histopathological studies of eyes removed after surgical treatment of retinal detachment]. AB - Among the examined eyes a cerclage was done in 13, in 5 an additional invagination, in 4 a posterior vitrectomy (2 eyes with membrane excision, 1 with injection of the SF6 gas and 1 with an injection of silicone). In 7 eyes the enucleation was caused by the atrophy of the eye ball, in 5 by absolute glaucoma and in 1 by suspected sympathetic ophthalmia. The most characteristic pathological changes were: inflammatory granuloma as a reaction for silicone band (4 eyes), scleral atrophy in the area of invagination (10 eyes), choroidal atrophy (12 eyes), proliferation of the pigment epithelium (10 eyes) and atrophy, fibrosis and proliferation of the glia in the retina. PMID- 1921223 TI - [Surgical treatment of retinal detachment with ora serrata dialysis in children]. AB - The clinical material comprises 38 eyes in 36 children aged 5-17 years. The goal of this work was a presentation of the efficacy of retinal detachment surgery in cases of ora serrata dialysis. Apposition of the retina after surgery was achieved in 97 p.c. of cases. The visual acuity higher than 0.1 was observed in 67.5 p.c. of cases. Cerclage of the eye performed in a large group of patients did not influence the functional results in comparison with the results obtained by other methods. PMID- 1921225 TI - [Orbital myositis]. AB - Four patients with unspecific myositis of the extraocular muscles were treated in the Ophthalmological Department Medical School in Bialystok in the period 1983 1988. The authors discuss the problems connected with the diagnosis and treatment of this pathological condition. Special attention is called to the new diagnostic methods. PMID- 1921224 TI - [Spontaneous detachment of the preretinal membrane in preretinal macular fibrosis]. AB - Preretinal macular fibrosis is one of the most frequently encountered conditions of the macula; it is based on the formation of a transparent or white-gray preretinal membrane. Usually these changes do not progress and persist without change for many years. In rare cases it may come to a spontaneous detachment of the preretinal membrane connected usually with an improvement of the visual acuity. Presented are 2 patients with preretinal macular fibrosis in whom--after a various duration of the disease--it came to a spontaneous detachment of the preretinal membrane. PMID- 1921226 TI - [Simultaneous stereograms of the fundus oculi]. AB - Stereophotograms and stereoangiograms of the fundus in selected pathological conditions are presented. The simultaneous performance of fundus stereograms are devoid of drawbacks and faults encountered in stereoscopic pictures registered in double time. A major consistency of the half-pictures results from an identical utilization of the focal depth and an uniform illumination in one exposure. In the fluorographic examination this method is a method of choice in the registration of a spatial picture throughout the examination. PMID- 1921227 TI - [Valentin Hauy--founder of the first school for the blind]. PMID- 1921228 TI - [Pathophysiology and therapy of lipid metabolism disorders in kidney diseases]. AB - Nephrotic syndrome, uremia, hemodialysis, peritoneal dialysis, and renal transplantation are accompanied by alterations in lipoprotein metabolism In nephrotic patients, total cholesterol, LDL, VLDL and triglycerides are elevated, while HDL may be increased, normal, or decreased. The pathophysiology includes increased hepatic synthesis of VLDL and cholesterol, decreased activity of lipoprotein lipase, and increased urinary excretion of HDL. The risk of coronary heart disease (CHD) is increased in nephrotic patients and elevated LDL cholesterol may contribute to this risk. Cholesterol lowering diet and drugs are indicated. Presently, Lovastatin and Simvastatin are the most potent cholesterol lowering drugs in nephrotic patients with good evidence of long-term safety. Most patients with impaired renal function or on hemodialysis have moderate hypertriglyceridemia due to decreased lipoprotein lipase activity. HDL may be slightly decreased. Although the risk of CHD is increased in these patients, triglyceride lowering drugs are not indicated, since no benefit can be expected. Peritoneal dialysis is accompanied by elevated VLDL in addition to hypertriglyceridemia. Reabsorption of large amounts of glucose from peritoneal dialysis fluid increases the carbohydrate load and stimulates hepatic VLDL synthesis. Cholesterol lowering therapy may be advantageous, but the experience is very limited. Side effects of lipid lowering drugs may be aggravated in renal failure. Total cholesterol, LDL, VLDL, and triglycerides are elevated in 50% of patients following renal transplantation. Corticosteroids and cyclosporin are major causes of hyperlipidemia. Cholesterol lowering therapy is indicated since the incidence of CHD is increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921230 TI - Nocturnal myocardial ischemia and cardiac arrhythmia in patients with sleep apnea with and without coronary heart disease. AB - To study the effect of apnea and hypoventilation-induced hypoxemia on the heart, we carried out polysomnographic recordings over 4 nights with electrocardiographic tracings in 30 patients with and without coronary heart disease. Evaluations of the data were based on the 2nd and 4th nights. In six subjects, five with coronary heart disease, we found 85 episodes of nocturnal ischemia, mainly during REM sleep (83.5%), high apnea activity, and sustained and progressive hypoxemia. Complex ventricular ectopy was observed in 14/13 patients (nights 2/4) and repetitive ventricular ectopy in 5/3. There was no significant difference in the quality and quantity of ventricular ectopy during wake and sleep states between the CHD group and the control group. In one patient ventricular bigeminy was observed only at a threshold of SaO2 below 60%. Bradyarrhythmia was made evident in four subjects from the CHD group and correlated mainly with apnea activity. We suppose that patients with sleep apnea and CHD are at cardiac risk because coronary heart disease can be aggravated by insufficient arterial oxygen supply due to cumulative phase of apnea and hypoventilation. The reduced hypoxic tolerance of the heart may lead to myocardial ischemia and increased electrical instability. PMID- 1921229 TI - Chlamydiae as pathogens--an overview of diagnostic techniques, clinical features, and therapy of human infections. AB - Chlamydiae are Gram-negative bacteria with obligate intracellular reproduction and disability to synthesize high-energy compounds such as ATP. Their cycle of development is unique among the prokaryotes: the host cells, mainly epithelial cells, are infected by so-called elementary bodies (EB) which undergo reorganization to form metabolically active reticulate bodies (RB). These RB multiply by binary fission, and after transition into infectious EB they are released within 48-72 hours. Chlamydiae cause prolonged subclinical infections of the conjunctiva, lung, cervix, and urethra. Complications in newborns are inclusion conjunctivitis, nasopharyngitis and pneumonia; in females, salpingitis, infertility, and perihepatitis; in male patients, epididymitis and prostatitis; and in both sexes, Chlamydiae-induced arthritis. Identification of the pathogenic agent confirms clinical diagnosis; tissue culture identification remains the diagnostic method of choice. Therapeutical drugs are tetracycline, erythromycin, josamycin, and in certain cases quinolone derivatives. PMID- 1921232 TI - Serratia infections in patients with neutropenia. AB - We report on six cases of sepsis caused by Serratia marcescens in patients with neutropenia. Four cases showed an additional involvement of the upper respiratory and digestive tract with oral and pharyngeal mucositis, haemorrhagic laryngo tracheo-bronchitis, and oedematous swelling of the face. One patient showed a Serratia marcescens carrier state in the pharynx over a period of months without neutropenia. The isolated strains showed a broad spectrum of resistance against antibiotics; only aztreonam and amikacin were effective in vitro against all isolates. PMID- 1921231 TI - Long-term effect of intensified insulin treatment on lipid parameters in diabetes mellitus type I. AB - Premature atherosclerosis is often found in patients with diabetes mellitus (DM) type I, and alterations in lipid metabolism seem to play an important role in the development of this complication. Intensified insulin therapy improves glycemic control parameters significantly. To evaluate the effect of this optimized insulin treatment (OIT) not only on glycemic control, but also on plasma lipids, 24 patients with DM type I (19 men and 5 women, 18 to 61 years) were switched from a standard insulin therapy to a regimen of OIT which has been maintained for more than 3 years now. After 2 years on OIT a reduction of HbA1c values from 8.1% to 7.5% (p less than 0.01) was accompanied by an increase in HDL cholesterol from 52 to 67 mg/dl (p less than 0.05) and a decrease of triglyceride levels from 319 to 67 mg/dl (p less than 0.001). At the end of the second year on OIT some of the patients exhibited a reversal of the favorable trend in HbA1c and lipid values. Intensified instructions regarding the implementation of OIT were therefore repeated and resulted in a renewed improvement of overall HbA1c, HDL cholesterol and triglyceride levels to 6.43%, 67 mg/dl, and 78 mg/dl, respectively. Our findings underline the value of OIT not only for glycemic control, but also for the control of plasma lipids considered to be major risk factors for coronary artery disease. PMID- 1921233 TI - [Therapy of terminal heart failure using heart transplantation]. AB - Heart transplantation (HTx) has now become an accepted treatment modality for end stage heart disease. The limited supply of suitable donor organs imposes constraints upon the decision of who should be selected for transplantation. Usually patients are candidates for HTx, who remain NYHA functional class III or IV despite maximal medical therapy. Further criteria are low left ventricular ejection fraction (less than 20%) with heart rhythm disturbances class IIIA-V (LOWN), which are associated with poor prognosis. Additionally, the suffering of the patient and also the course of heart failure are essential for judging the urgency of HTx. Contraindications are absolute in patients with untreated infections, fixed pulmonary vascular resistance (PVR) above 8 WOOD-degrees, severe irreversible kidney and liver disease, active ventricular or duodenal ulcers and acute, psychiatric illness. HTx is relatively contraindicated in patients with diabetes mellitus, age over 60 years, PVR above 6 WOOD-degrees and an unstable psychosocial situation. To prevent rejection of the transplant heart, live-long immunosuppressive therapy is needed. Most immunosuppressive regimes consist of Cyclosporine A and Azathioprine (double drug therapy) or in combination (tripple drug therapy) with Prednisolone. For monitoring of this therapy, control of hole blood cyclosporine A level and white blood count is needed. Rejection episodes can be suspected if there is a greater than 20 mmHg decrease of systolic blood pressure, elevated body temperature, malaise, tachycardia or heart rhythm disturbance. The diagnosis of cardiac rejection can be established by endomyocardial biopsy. Measurement of the voltage of either the surface or intramyocardial ECG, echocardiography with special consideration to early left ventricular filling time as well as immunological methods are additionally used tools. Graft sclerosis as the main risk factor of the late transplant period remains an unsolved problem. PMID- 1921234 TI - The natural course of atrial septal defect in adults--a still unsettled issue. AB - Atrial septal defect is the most frequently encountered major congenital cardiac disorder in the adult population, with a prevalence of 0.2 to 0.7 per thousand. Several patients tolerate large unrepaired defects for 80 years or even longer without serious disability. However, it is assumed that, as a rule, atrial septal defect reduces life expectancy, the average age at death not exceeding 50 years. This estimation is based on studies derived mainly from necropsy series or from the admission profile of patients undergoing late operative repair. The onset of atrial fibrillation, with an incidence ranging from 13 to 52 percent among patients older than 40 years, as well as the progression of pulmonary arterial hypertension in up to 53 percent of patients, results in congestive heart failure and functional limitation. On the other hand, very few longitudinal studies thus far have directly and systematically followed the course of adults with unrepaired defects. Thus, many issues regarding the natural history and prognosis of atrial septal defect still remain unresolved. Follow-up series of older patients with nonoperated defects could yield valuable information even in an era when routine early surgical closure is increasingly being recommended. PMID- 1921236 TI - Identification of a silent point mutation in the LDL-receptor gene by direct DNA sequencing. AB - To study the allelic variation at the human LDL-receptor gene locus in a number of individuals with familial hypercholesterolemia, a protocol was applied for direct sequence analysis of genomic DNA. The asymmetric polymerase chain reaction (PCR) was used to synthesize single-stranded DNA. Sequencing was carried out with modified T7 DNA polymerase (Sequenase version 2.0, United States Biochemical) after purification of the amplification product with a glass powder adhesion method. The method is sensitive enough to identify the heterozygous state of allelic variation and bypasses cumbersome cloning and subcloning procedures. Here we report the occurrence of a guaninine-to-adenine change in the codon for amino acid 655. However, the glycine residue is not replaced by the base change at this position, and the mutation observed here does not represent the underlying genetic defect of the LDL-receptor defect in this individual. Preliminary data suggest that this mutation represents a rare genetic variation. PMID- 1921235 TI - [Decreased plasma carnitine in Type I diabetes mellitus]. AB - Realizing the importance of carnitine for the lipid and carbohydrate metabolism and the possible role for glucose utilization and myocardial function carnitine concentrations in type I and type II diabetic patients in plasma, erythrocytes and 24 h urine were determined. The plasma levels of carnitine were significantly diminished in type I diabetic patients compared to controls, while carnitine concentrations in erythrocytes and 24 h urine did not differ from controls. Plasma carnitine levels did not change significantly during the diurnial profile. No correlation between HbA1c and carnitine levels was observed in the diabetic patients. PMID- 1921237 TI - Fibrin degradation product D-dimer in the diagnosis of pulmonary embolism. AB - The study objective was to determine the specificity and sensitivity of plasma concentrations of D-dimer, a fibrin degradation product, as a marker for ongoing thrombotic and thrombolytic events in pulmonary embolism. A prospective study was performed in 74 patients with suspected pulmonary embolism who appeared in the emergency room with dyspnea and/or chest pain. The presence of pulmonary embolism was established by positive findings either in pulmonary angiography or lung scan. D-dimer concentrations were determined in all patients. In 11 patients with positive pulmonary angiography, D-dimer concentrations were monitored for 6-12 days. D-dimer concentrations were determined by a quantitative enzyme-linked immunoassay. Plasma probes of 26 patients (16 with/10 without positive pulmonary angiography) were re-assayed with a semiquantitative latex agglutination assay. D dimer levels were significantly higher in patients with pulmonary embolism (greater than 1000 ng/mL in 41 out of 43) than in those without (less than 1000 ng/mL in all 21 patients) (p less than 0.01). The sensitivity and specificity for the ELISA were found to be 95% and 100%, respectively, for establishing the diagnosis of pulmonary embolism. In the latex assay the values were 81% and 60%, respectively. It is concluded that in patients with dyspnea and/or chest pain, determination of D-dimer in plasma by ELISA adds a valuable tool to the noninvasive diagnostic procedure for pulmonary embolism. From the time-course of D-dimer values we conclude that this assay might be valuable up to at least 6 days after symptom onset. The assay, however, is unreliable in malignancies or after surgery. PMID- 1921238 TI - The prevalence of homocysteinemia and hypercholesterolemia in angiographically defined coronary heart disease. AB - Total serum homocysteine and cholesterol levels were determined in 163 male patients with typical angina who were subjected to coronary angiography. The prevalence of homocysteinemia in coronary heart disease (CHD) was 41.9%. Serum homocysteine levels were significantly elevated (p less than 0.05) in patients with major occlusion in two or three coronary arteries. Furthermore, the prevalence of homocysteinemia correlated positively (p less than 0.05) with the number of coronary vessels that were occluded. The prevalence of hypercholesterolemia was 34.9%, but, in contrast to homocysteinemia, no graded strength of association with the number of stenotic coronary arteries could be demonstrated. The results suggest that homocysteinemia may contribute significantly to the development of coronary heart disease. PMID- 1921240 TI - Sinusoidal endothelial liver cells in vitro release endothelin--augmentation by transforming growth factor beta and Kupffer cell-conditioned media. AB - Endothelin is the most potent vasoconstrictor peptide known today. Using a radioimmunoassay for endothelin, we measured immunoreactive endothelin in culture media of guinea pig sinusoidal endothelial liver cells and human umbilical vein endothelial cells. A time-dependent release of immunoreactive endothelin by confluent sinusoidal endothelial liver cells in culture was found. Sinusoidal endothelial liver cells produced similar amounts of immunoreactive endothelin as umbilical vein endothelial cells, about 900 pg/microgram DNA per 24 h. In the presence of transforming growth factor beta a dose-dependent increase of immunoreactive endothelin release was measured. The maximal increase of 50% was found at a concentration of 1 ng transforming growth factor per ml. To a similar extent Kupffer cell-conditioned media augmented the release of immunoreactive endothelin by sinusoidal endothelial liver cells, especially when Kupffer cells had been stimulated by endotoxin. Endotoxin itself did not alter the release of immunoreactive endothelin. Endothelin released by sinusoidal endothelial liver cells might influence the pericytes of the liver, i.e., the Ito-cells. PMID- 1921239 TI - [Thrombocyte transfusion: clinical aspects, follow-up and complications]. AB - Thrombocytopenia is the most common cause of bleeding tendency, and, if due to impaired platelet production, is best treated by platelet transfusions. Prophylactic transfusions for asymptomatic patients should be considered if platelet count is below 20,000/microliters. However, if bleeding occurs or surgery is inevitable, platelet count should be maintained above 50,000/microliters. The benefit of platelet transfusions has to be balanced against risks like fever, infections and haemolysis. The effectiveness of platelet transfusions should be examined after 1 and 24 hrs by measuring the corrected count increment (CCI). Not only alloimmunization is a reason for unsatisfactory platelet increments. A poor CCI can also be due to fever, sepsis, hepato-splenomegaly or special drugs, which must be taken into account when assessing the demand for platelet transfusions. PMID- 1921241 TI - [Effect of zinc substitution on lymphocyte subsets and cellular immune function in hemodialysis patients]. AB - Infection is a major cause of morbidity and mortality in patients undergoing hemodialysis for end stage renal disease. Low plasma zinc levels have been associated with immunodepression in these patients. In a randomized, placebo controlled double-blind cross over study, plasma zinc levels, delayed hypersensivity to 7 Antigens (Merieux-Multitest), absolute lymphocyte counts, T- and B-lymphocytes, suppressor-T and helper T-cells and natural killer cells were studied in 25 hemodialysis patients before, during and after intravenous zinc supplementation for 8 weeks. The hemodialysis patients had significantly lower predialysis plasma zinc concentrations compared to 76 healthy controls (74 +/- 12 vs. 126 +/- 28 mcg/dl, p less than 0.001). The plasma zinc concentrations increased to the normal range during the treatment period. Lymphocyte subtype analysis showed a significant decrease of suppressor-T cells and an increase of the helper-T/suppressor-T ratio (2.09 +/- 0.26 vs. 3.18 +/- 0.48, p less than 0.05) after zinc supplementation. Delayed hypersensivity to intradermal antigens increased significantly only after zinc treatment (2.0 +/- 0.7 vs. 5.8 +/- 1.7, p less than 0.05), not after placebo. The changes were reversible after finishing the zinc treatment. It is concluded, that plasma zinc levels are reduced in hemodialysis patients and that the substitution of zinc restores some of the depressed immune functions in these patients. PMID- 1921242 TI - Demonstration of specifically sensitized lymphocytes in patients treated with an aqueous mistletoe extract (Viscum album L.). AB - Lymphocytes of 25 patients treated with an aqueous mistletoe extract (Viscum album L.) for up to 6 months (group 1), up to 2 years (group 2), and more than 2 years (group 3) were examined in 3- and 7-day cultures for specifically sensitized lymphocytes. The whole extract (HM), the lectin-polysaccharide fraction (HM-LP), and the 'viscotoxin' fraction (HM-V) were added at concentrations ranging from 0.5 micrograms to 12.5 mg extract/ml. Lymphocytes from four of the nine group 2 patients and five of the ten group 3 patients reacted specifically with HM and HM-LP at an optimal dose of 5.0 mg/ml, but did not react with HM-V. Stimulation indices varied between 1.6 and 16. In the patients of group 3 this effect was observed only when their lymphocytes were co stimulated in the 3-day cultures with phytohemagglutinin (PHA), in contrast to the four patients of group 2 who reacted only in the 7-day cultures with HM-LP without PHA co-stimulation. Patients' lymphocytes had to be protected from mistletoe lectin-induced cytotoxicity by the addition of their own sera containing anti-mistletoe lectin antibodies. Lymphocytes from tumor patients (n = 18) never treated with mistletoe extracts and healthy individuals (n = 18) showed no specific proliferative response when tested in 3- and 7-day cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921243 TI - [Perimyocarditis in influenza A virus infection]. AB - A 48-year old man was admitted with suspected acute myocardial infarction because of severe precordial pain and monophasic ST-elevations in the ECG. The patient's history of an ongoing infection, the localization, extent, and course of the ECG changes as well as the development of a pericardial effusion suggested viral perimyocarditis. The diagnosis was supported by a significant rise of antibodies (seroconversion) against influenza A virus. PMID- 1921244 TI - Remarkable improvement of neuropsychiatric symptoms in HIV-infected patients after AZT therapy. AB - Treatment of neuropsychiatric symptoms with AZT (Azidothymidine) seems to be effective in many AIDS patients. In earlier studies, 204 of 525 patients treated with AZT showed neuropsychiatric improvement. In this presentation, two patients with affective disorder and dementia are described. Both patients showed remarkable improvement of their severe psychiatric symptoms after AZT. The authors recommend treatment of AIDS-associated dementia and psychoorganic symptoms with AZT. PMID- 1921245 TI - Are the conclusions of INTERSALT applicable to the German population? AB - We distinguish determinants of individual blood pressure elevations and those which influence shape and location of entire population distributions, i.e. epidemiological determinants. Individual and epidemiological determinants are not necessarily the same. Identification of the latter may be used to develop population wide prevention strategies that carry a great potential of reducing the public burden of cardiovascular morbidity and mortality. Salt has long but controversially been suspected as a major etiologic agent in hypertensive populations. For the first time the INTERSALT study tried in a systematic and standardized way to assess the salt-BP association in individuals and across 52 populations in 32 countries. The observed within center relations to systolic and more so to diastolic BP were largely inconsistent in direction and magnitude indicating probable non-uniformity of the salt effect. In this case, statistical pooling of single effect estimates may have lead to invalid conclusions. Across center analyses found no relevant relation of median sodium excretion to median BP values or hypertension prevalence and hence no evidence for salt as an epidemiologic BP determinant. It is concluded that the INTERSALT evidence is not sufficient to warrant salt restriction in the general population. This contrasts with consistent and quantitatively relevant individual and population associations of body mass index with blood pressure in INTERSALT. Considering its potentially multifactorial preventive effects, BMI reduction seems to be a more pragmatic public health measure for the German population. PMID- 1921246 TI - Dietary salt intake and hypertension. AB - There is much circumstancial and some direct evidence in humans to suggest that a high consumption of salt predisposes communities and individuals to the development of essential hypertension. Restriction of salt intake in the diet lowers blood pressure in many subjects with high blood pressure and this fall in blood pressure is mediated in part by a diminished renin response to sodium restriction as hypertension develops. The effect of sodium restriction, like diuretics, is additive to many blood pressure lowering drugs, particularly those that inhibit the renin system such as beta-blockers and angiotensin converting enzyme inhibitors. PMID- 1921247 TI - Salt restriction, a sceptic's viewpoint. AB - In the light of the proposal that dietary salt intake should be reduced as a community health care measure designed to lower blood pressure and consequently mortality and morbidity from stroke and heart disease, the evidence that there is a link between salt intake and blood pressure is reviewed. In addition the effects of salt restriction on mild hypertension are surveyed as is the feasibility of sustaining a community-based campaign to reduce salt intake. It is concluded that whilst it would be possible to mount a concerted health care programme directed towards lowering the salt intake of the general population the benefits in terms of blood pressure would be extremely small. The impact on stroke and heart disease is unknown and possible adverse effects have not been examined. PMID- 1921248 TI - Sodium and blood pressure: a review of the evidence from controlled trials of sodium reduction and epidemiological studies. AB - Evidence from controlled trials of sodium reduction and epidemiological studies are consistent in showing that lower urinary sodium excretion is associated with lower blood pressures (BPs) and quantitatively they give similar estimates of effect. An overview of randomised controlled trials gave the estimate that a reduction in sodium excretion averaging 70 to 75 mmol per day lowered BP in hypertensives by 4.9 mmHg systolic and 2.6 mmHg diastolic (p less than .001), and by 1.7 mmHg (p less than .001) and 1.0 mmHg (p less than .01) respectively in normotensives. An overview of within-population epidemiological studies, after correction for intra-individual variability in sodium excretion, gave a pooled (simple) regression estimate that 100 mmol lower sodium was associated with BP lower by 3.7 mmHg systolic and 2.0 mmHg diastolic (p less than .001); and the corrected pooled within-centre regression estimate from INTERSALT, with adjustment for age and sex, was that 100 mmol lower sodium was associated with BP lower by 3.5 mmHg systolic and 1.5 mmHg diastolic (p less than .001), reducing to 2.2 mmHg (p less than .001) and 0.1 mmHg respectively after adjustment for other confounders. Across the centres in INTERSALT, average sodium excretion was positively and significantly related to slope of BP with age, such that 100 mmol lower sodium was associated with a 9 mmHg lower rise in systolic BP from age 25 to age 55 (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921249 TI - Does salt sensitivity exist? PMID- 1921250 TI - [Further advances in the salt sensitivity hypothesis in man]. AB - The hypothesis, proposed by us since 1981, that genetically determined salt sensitivity exists in the normotensive population has been confirmed by other groups. We propose that in salt sensitive subjects an augmented upregulation of alpha-2 combined with simultaneous downregulation of beta-2 adrenoceptors by a high salt diet (resulting in an increase in the "operative" adrenoceptor ratio) is responsible for the rise of blood pressure. In salt resistant subjects the "operative alpha-2/beta-2 adrenoceptor ratio" does not increase on a high salt intake. The adrenoceptor changes in salt sensitive subjects probably lead to an increased central sympathetic outflow (through receptor changes in certain brain areas) and to simultaneous enhanced end-organ response in resistance vessels and in the kidney, causing enhanced vasoconstriction and enhanced sodium reabsorption. Long term follow up of salt sensitive normotensives will show, whether they develop "essential hypertension" in the future. PMID- 1921251 TI - Abnormal acid-base regulation in salt-sensitive normotensive man. AB - Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. Studies in normotensive salt-sensitive men have likewise demonstrated slightly but significantly lower arterial pH and bicarbonate levels, relating salt-sensitivity to the presence of a relative acidosis in man. The administration of alkalinizing sodium salts such as sodium bicarbonate or citrate have been shown to have no effect on or to even lower blood pressure in patients with essential hypertension. Possible factors contributing to the perturbation in acid-base status include an enhanced Na+/H(+)-antiport activity, lower intracellular pH levels and altered renal electrolyte handling as found in rat models of hypertension and in patients with essential hypertension. PMID- 1921252 TI - Potential deleterious impact of dietary salt restriction on cardiovascular risk factors. AB - Excessive intake of dietary salt is thought to promote hypertension in Western societies, and some have recommended salt restriction for the general population. While such restriction is thought to be innocuous, few studies have examined the impact of dietary salt on cardiovascular risk factors other than blood pressure. In a randomized, placebo-controlled, doubly blinded comparison of one week periods of 20 vs. 208 mEq/d NaCl intake in 27 hypertensives and normotensives, we found that salt restriction had no significant effect on blood pressure (p = 0.45) and a generally adverse impact on risk factors for cardiovascular disease. Stringent, short-term dietary salt restriction caused increases in total and low density lipoprotein cholesterol that were of borderline significance (p = 0.07). These lipid effects probably resulted from plasma volume contraction, as they were coincident with significant rises in hemoglobin (p = 0.01), hematocrit (p less than 0.001), total protein (p less than 0.01) and albumin (p = 0.01); such changes may act together to increase whole-blood viscosity. In addition, plasma norepinephrine (p = 0.02), fasting plasma insulin (p = 0.02) and glucose-to insulin ratio (p = 0.01) increased during salt restriction. The potentially adverse impact of dietary salt restriction on the risk factor profile for cardiovascular disease suggests that further studies are necessary before a reduction in dietary salt intake can be prescribed for the general population. PMID- 1921254 TI - Heterogeneity of blood pressure responses to salt restriction and salt appetite in rats. AB - In contrast to a widely held belief, the response of blood pressure to even marked changes of salt (NaCl) intake is extremely heterogeneous in different strains of laboratory rats. Like in healthy humans, it is rather difficult to induce an increase or a decrease of blood pressure in normotensive rats by the manipulation of dietary salt consumption within a reasonable range. Moreover, severe NaCl restriction is sometimes associated with a paradoxical rise in blood pressure. No direct relation appears to exist between salt appetite and blood pressure. We showed that salt appetite was increased after dietary NaCl restriction in normotensive Wistar rats compared with normotensive Fischer 344 rats. The latter had a high renin status which was not sensitive to changes in dietary salt. An altered peripheral or central renin metabolism in this rat strain might be partly responsible for their relative lack of salt appetite and could be related to their notable lack of blood pressure sensitivity to dietary NaCl. PMID- 1921253 TI - Short-term dietary sodium restriction increases serum lipids and insulin in salt sensitive and salt-resistant normotensive adults. AB - Evidence suggests that dietary salt reduction similar to diuretic therapy may adversely affect lipid and glucose metabolism. We studied 147 non-obese normotensive subjects (60 females and 87 males) aged 19-78 years who entered a single-blind crossover trial and were randomly assigned to a low salt diet of 20 mmol or a high salt diet of 300 mmol sodium per day, for 7 days each. Sodium restriction lowered mean arterial blood pressure (MAP) by a mean of 7.5 mmHg in 17% (salt-sensitive), had no hemodynamic effect in 67% (salt-resistant) and raised MAP by a mean of 6 mmHg in 16% of the subjects (reverse reactors). With dietary salt restriction serum total- and LDL-cholesterol as well as serum insulin and uric acid concentrations increased significantly in all three groups. The largest increases in total (10%) and LDL- (12%) cholesterol occurred in the reverse reactors. Salt-sensitives had significant higher lipoprotein(a) values than the other two groups. Salt-restriction had no significant effect on this parameter. Plasma renin activity, as well as plasma aldosterone and noradrenaline concentrations rose in all three groups during the low salt diet, the largest increases being observed in the reverse reactors. Short-term sodium restriction in normotensive adults has unfavourable effects on lipid and glucose metabolism, especially in subjects who do not derive hemodynamic benefit. Further studies are necessary to examine the effects of more moderate salt reduction for longer periods on the risk factor profile for cardiovascular disease before a low salt diet can be regarded as a safe public health measure for the general population. PMID- 1921255 TI - The influence of oral potassium citrate/bicarbonate on blood pressure in essential hypertension during unrestricted salt intake. AB - In several trials, a blood pressure lowering effect of potassium chloride could be demonstrated. However, it is not known if other potassium salts are also effective. In a randomized cross-over trial, 12 patients with essential hypertension were treated for 8 weeks with placebo and 120 mmol potassium per day. Potassium was given together with 50% citrate and 50% bicarbonate as anions. Urinary potassium excretion rose from 61.8 +/- 8.1 to 166.7 +/- 21.2 mmol/24 hours during potassium supplementation. However, blood pressure and heart rate remained unchanged when compared to placebo. Non-chloride potassium salts may not be effective in lowering blood pressure in essential hypertension. Since potassium rich foods like fruits and vegetables contain potassium mostly as non chloride salts, it appears to be premature to recommend a high dietary potassium intake as a mean to treat elevated blood pressure. PMID- 1921256 TI - [The role of chlorides in sodium-induced "salt-sensitive" hypertension]. AB - Older and more recent evidence indicates that the anion accompanying sodium plays an important role in determining whether or not the administration of a sodium load leads to an increase arterial in blood pressure. This review describes animal and human studies in which blood pressure responses to sodium administration, with or without chloride, were determined. The evidence suggests that sodium and chloride together combine to increase blood pressure in salt sensitive models and patients. The observations have relevance to the understanding of the pathogenesis of hypertension. They also have clinical relevance, since some food sources may have an abundance of one or the other ion. PMID- 1921258 TI - The colonic patch graft as a new technique of enteroplasty: histological observations and absorptive functions. AB - BACKGROUND: A colonic patch graft technique which consists of a three-staged procedure, was developed in order to diminish ileostomy complications and to reconstruct rectoanal function in patients with extensive aganglionosis. The basic data on creation of the colonic patch graft remains uncertain. METHODS: Using 20 experimental dogs, a colonic patch graft was created by forming a longitudinal side-to-side ileocolostomy, followed in 10 weeks by severance of the colonic mesentery which feeds the anastomosed colon segment. Five weeks after division of the primary blood supply, histological studies of the walls of the colonic graft were carried out in 10 dogs. Effect of severance of the colonic mesentery on water and electrolytes absorption through the ileocolostomy segment was evaluated by single perfusion method in 10 dogs. RESULTS: The significant abnormality noted was marked thickening of the submucosal layer secondary to persistent lymphstasis. Other layers of the bowel wall were not abnormal including the mucosa, muscle layers, and intramural ganglion cells. The severance of the colonic mesentery belonging to the ileocolostomy segment did not affect its absorptive capacity for water and electrolytes. CONCLUSIONS: The histological findings support the observation that absorptive function in the mucosa of the colonic patch graft is not significantly disturbed, although lymphstasis is observed in the submucosa. PMID- 1921257 TI - [Heterogenicity of hypertension: the various effects of electrolyte intake]. AB - Nonpharmacologic approaches to patients with hypertension are a worthwhile avenue to treatment as well as a laudable public health goal. Reduced salt intake has been the primary dietary measure. However, recently attention has also been directed at potassium, calcium, magnesium, and the anions accompanying these cations. Further, the importance of total caloric intake and confounding dietary variables such as alcohol consumption have been appreciated. It is important to recognize that nutrients are not ingested in isolation, but rather as interactive constituents of a total diet. This principle may account for some of the heterogeneity of the human blood pressure response to variations of individual electrolyte intake. Moreover, failure to appreciate this heterogeneity and interactive effects may result in other than the desired effect in the population at risk. PMID- 1921259 TI - The role of lipid peroxidation in the genesis of vasospasm secondary to subarachnoid hemorrhage. AB - The aim of this study is to find out the possible trigger role of lipid peroxidation in vasospasm. Haemoglobin-free washed erythrocyte membranes (erythrocyte ghost) corresponding to 2.5 mg membrane protein was mixed with 0.5 umol NADPH 3 umol ADP, 4 umol ferrous sulphate and injected into the cisterna magna of cats to stimulate lipid peroxidation in vivo (Group 1). The second group was injected lml/kg whole blood and the control group 1 ml/kg saline. Angiographic studies revealed significant vasospasm in five cats in group 1. Severe vasospasm was seen in six cats in group 2. A significant increase in lipid peroxidation was observed in groups 1 and 2, compared to the control group. These results may suggest that free radical products may play an important role in the complex genesis of vasospasm in subarachnoid haemorrhage. PMID- 1921260 TI - Southern blot and PCR analyses of dystrophin gene deletions in Japanese patients with Duchenne muscular dystrophy. AB - We have analyzed 34 Japanese patients of 31 families with Duchenne muscular dystrophy (DMD) by Southern blot and PCR (polymerase chain reaction) to detect large deletions in the genomic dystrophin gene on the X chromosome. Fifteen families (48%) had various deletions in the dystrophin gene by Southern blot analysis using the dystrophin cDNA probes 1-2a, 2b-3 and 8 which effectively covers the high-risk regions of deletion. Lengths and positions of the gene deletions detected were variable. Although there were no common deletions of exons in the gene of the DMD patients examined with the above cDNA probes, the deletion frequency of each exon was almost the same as the result previously reported in Caucasian DMD patients. The PCR method was also applied to confirm gene deletions in 9 cases from the above 15 families by amplifying 6 different regions of the dystrophin gene. Eight out of 9 DMD cases had gene deletions at the same genomic regions as found by Southern blot analysis. In a single DMD case, the Southern blot analysis indicated the exon 12 deletion, but PCR successfully amplified a 331 bp DNA fragment containing exon 12 and flanking introns. This difference may arise by a large deletion except for the above small 331 bp sequence in the HindIII digests of dystrophin gene. PMID- 1921261 TI - RAS gene mutations in multiple myeloma and related monoclonal gammopathies. AB - The presence of RAS gene mutations in precancerous lesions suggests that they participate in the early stages of neoplastic development. Furthermore, neoplastic progression from monoclonal gammopathy of undetermined significance (MGUS) to overt multiple myeloma (MM) have been frequently observed. These observations prompted us to study the pathogenetic role of RAS genes in MM and related monoclonal gammopathies. DNA from 18 patients with monoclonal gamma globulinemia including 12 MM were investigated for the presence of N- and K-RAS gene mutations by polymerase chain reaction (PCR)/oligonucleotide hybridization. Mutations involving codons 12, 13 or 61 of N-RAS gene were identified in 3 of the 12 MM patients, 1 of the solitary plasmacytoma patients and none of the 3 of the MGUS patients. In the case of plasmacytoma, RAS mutations were detected in his bone marrow specimens. PMID- 1921262 TI - Pressure measurement in pancreatic duct and biliary duct system in dogs with acute pancreatitis. AB - We investigated the intraductal pressures of the pancreatico-biliary system in dogs with acute pancreatitis. Intraductal pressures were measured by the method of perfusion manometry. After the perfusion with saline (the common bile duct (CBD: 0.8 ml/min, the pancreatic duct (PD: 0.2 ml/min], two parameters, the residual pressure (RP) and the pressure decay time (DT), were measured before and after the induction of acute pancreatitis. The RP of the PD was elevated after inducing severe pancreatitis. There were statistically significant difference of the RP of the PD between severe and moderate pancreatitis. In addition the DT of the PD was also prolonged in severe pancreatitis. There were significant difference of the DT of the PD between moderate and severe pancreatitis. On the other hand the RP of the CBD was also elevated in severe pancreatitis. There were statistically significant difference of the RP of the CBD between severe and moderate pancreatitis. However there was no significant difference between them concerning the DT of the CBD. The histological examination of periampullary area in severe pancreatitis showed measurable inflammatory changes (papillitis). However there was no such finding in moderate pancreatitis. Our results suggest that pressure measurement in the PD is useful for predicting the severity of acute pancreatitis because the pressure of both the PD and the CBD were elevated in severe pancreatitis but not in moderate pancreatitis and this difference is mainly due to the difference of the influence of pancreatitis to the periampullary region. PMID- 1921263 TI - Inhibition of cellular proliferation in human T lyophotropic virus type I (HTLV I)-infected T cells from patients with HAM by steroid hormones and cyclosporin A. AB - The effects of steroid hormones and Cyclosporin A (CsA) on de novo DNA synthesis in four human T lymphotropic virus type I (HTLV-I)-infected T cell lines from patients with HTLV-I-associated myelopathy (HAM) were investigated. These T cell lines were characterized by helper/inducer phenotypes and expressed IL-2-receptor (Tac) and HLA-DR antigen in high percentages. Three of the four cell lines had their de novo DNA synthesis inhibited by steroid hormones (dexamethasone and 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3)) and CsA in a dose dependent manner. The inhibitory effects arose 24 hours after initiation of incubation with either steroid hormones or CsA. The forth cell line was not inhibited by these reagents. It also revealed through the use of an in vitro assay utilizing the human IL-2 dependent cell line, Sez 627, that none of these T cell lines secrete IL-2 in detectable volumes. In order to clarify the mechanism of the inhibitory effects of steroid hormones and CsA, among these 4 cell lines H-89-59, insensitive to the reagents, and H-109, sensitive to them, were used for northern blotting analysis. C-myc gene expression was demonstrated both in H-89-59 and H-109. 1,25(OH)2D3 and CsA suppressed c-myc expression in H-109 as well as cell proliferation. In H-89 59, however, neither expression of c-myc nor cell proliferation was suppressed. On the other hand, the level of HTLV-I gene transcripts was not changed by these agents. Hence, inhibition of cellular proliferation by these reagents was not caused by the inhibition of HTLV-I p40(x) gene but by inhibition of transcriptional factors such as c-myc products. PMID- 1921264 TI - [Home nursing care. II. Home nursing service system in Korea]. PMID- 1921265 TI - [The effect of immobility--on the cardiovascular system, respiratory system, metabolism and nutrition]. PMID- 1921267 TI - [Effects of immobility: pressure sores and their management]. PMID- 1921266 TI - [The effect of immobility--on the musculoskeletal system, on the bowel and urinary elimination]. PMID- 1921268 TI - [A case study of a patient with bone marrow transplantation]. PMID- 1921269 TI - [Concepts of caring and caring as a concept]. PMID- 1921270 TI - [A study on need assessment and model development for home nursing care]. PMID- 1921271 TI - [Home nursing care. II. Home health care and visiting health care--home health care, where are we heading?]. PMID- 1921272 TI - [Home nursing care. III. Home care for the mobility disabled--a case study of a spinal cord injury client]. PMID- 1921273 TI - [Development of theory for community health nursing]. PMID- 1921274 TI - [Theory development for community nursing in Korea]. PMID- 1921275 TI - [The right to die and the living will: Missouri status]. PMID- 1921276 TI - [Nursing and study of interstitial pneumonia in the patient with a rejected transplanted kidney]. PMID- 1921277 TI - [The identification of high-risk pregnancy, using a simplified antepartum risk scoring system]. AB - This study was carried out to assess the problems with the pregnant women, and check out the risk-factors in the high-risk pregnancies, using a simplified antepartum risk-scoring system, which was revised from Edwards' scoring system to be suitable for Korean situation. This instrument was included 4 categories, demographic, obstetric, medical and miscellaneous factors. This survey was based on the 1300 pregnant women who were admitted, from Jan. 1, 1988, to May 31, 1990, Chung Ang Medical Center. Data were collected from June 25, 1990 to July 7, 1990. Data was analyzed by x2-test, F-test, Pearsons correction, using statistical package SAS in NAS computer system, KIST. The results of the study were as follows; 1. 1313 infants were deliveried of these 560 infants (42.7%) were born to mothers with risk-scores greater than 7, and 753 infants (57.3%) were born to mothers risk-scores less than 7. 2. Maternal age, parity, education level, of the demographic factors were significant relation statistically to identify the high risk pregnancies (X2 = 20.88, 42.87, 15.60 P less than 0.01). 3. C-section, post term, incompetent cervix, uterine anomaly, polyhydramnios, congenital anomaly, sensitized RH negative, abortion, preeclampsia, excessive size infant, premature, low birth weight infant, abnormal presentation, perinatal loss, multiple pregnancy, of the obstetric factors were significant relation statistically to identify the high risk-pregnancies. (chi 2 = 175.96, 87.5, 16.28, 21.78, 9.46, 8.10, 6.75, 22.9, 64.84, 6.93, 361.43, 185.55, 78.65, 45.52, P less than 0.01). 4. Abnormal nutrition, anemia, UTI, other medical condition (pulmonary disease, severe influenza), heart disease, V.D., of the miscellaneous and medical factors, were significant relation statistically to identify the high risk-pregnancies. 5. Premature, low birth weight infant, contracted pelvis, abnormal presentation, of the risk factors were significantly related with Apgar score at 1 & 5 minute after birth and neonatal body weight. 6. Apgar score at 1 & 5 minute after birth and neonatal body weight were significantly negative correlated with risk-score. 7. There were statistically significant difference between risk-score and Apgar score at 1 & 5 minute after birth, 3 group (0-3, 4-6, above 7), and neonatal body weight, 2 group (below 2.5 kg, the other group) (F = 104.65, 96.61, 284.92, P less than 0.01). 8. Apgar score at 1 & 5 minute after birth (below 7), and neonatal body weight (below 2.5 kg), were significant relation statistically with risk score. (chi 2 = 65.99, 60.88, 177.07, P less than 0.01) were 60.8%, 60%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1921278 TI - [Home nursing care. III. Home nursing for the patient with impaired mobility (due to musculoskeletal disorder)]. PMID- 1921279 TI - [The future of geriatric care. A dialogue with geriatric nurses]. PMID- 1921280 TI - [Biographical knowledge in the care of the aged]. PMID- 1921281 TI - [Everyday life in geriatrics]. PMID- 1921282 TI - [Aging--losses in my life]. PMID- 1921283 TI - [Patient-oriented hospital--utopia or attainable objective?]. PMID- 1921284 TI - [Board for the nursing professions. Data, facts and arguments]. PMID- 1921285 TI - [Addiction in the work place: inconspicuous and more and more frequent]. PMID- 1921287 TI - [Who is an employee?]. PMID- 1921286 TI - [The Palestinian problem: from the headlines but not out of this world. Children without hope]. PMID- 1921288 TI - [Complaints at the transfer into home care--an investigation. "... not only was the catheter missing, there was no trace of the prescription"]. PMID- 1921289 TI - [The four phases of mourning--a description. The helpful handling of grief]. PMID- 1921290 TI - [2 nurses attend the Big Council of Vaud. Past the parties, a common profession]. PMID- 1921291 TI - [Professional education in the Vaud in the health fields. Games of money and power]. PMID- 1921292 TI - [Border nurses and salaries. The Swiss magnet]. PMID- 1921293 TI - [Nurses increase their influence by regrouping. To be recognized as a social force]. PMID- 1921295 TI - [The written application]. PMID- 1921294 TI - [Explosion of health care costs: 13 theses. Myths and reality]. PMID- 1921296 TI - [Abuse of power facing the aged. The courage to say "No"]. PMID- 1921297 TI - [The nurse: expert, intermediary, informer, helper; power as a relationship]. PMID- 1921298 TI - [To avoid wasting wealth and power. More powerful than money: knowledge]. PMID- 1921299 TI - [Patients' associations as a counter power. The voiceless in psychiatry]. PMID- 1921300 TI - [Nursing in China--visiting a cancer center. Lack of patient information]. PMID- 1921301 TI - [Dealing with the patients' modesty]. PMID- 1921302 TI - [Supervision in nursing education, especially in pediatrics]. PMID- 1921303 TI - [Epidemiology of HIV and AIDS and the danger of infection of medical personnel]. PMID- 1921304 TI - [What is the effect of inodilators? Acting principle and therapeutic potentials]. PMID- 1921305 TI - [Asthma caused by occupational exposure]. PMID- 1921306 TI - [The Elements of Nursing. A model for nursing in rehabilitation by Nancy Roper]. PMID- 1921307 TI - [Nursing activities must be documented]. PMID- 1921308 TI - [Is there a connection between cancer and nutrition?]. PMID- 1921309 TI - [Nursing aspects in caring for AIDS patients]. PMID- 1921310 TI - [AIDS immunoprophylaxis: chances and risks in the development of an AIDS vaccine]. PMID- 1921311 TI - [Rehabilitation of children and adolescents after head injuries]. PMID- 1921312 TI - [Consolation--not empty pronouncements]. PMID- 1921313 TI - Segregation of genes from donor strain during the production of recombinant congenic strains. AB - Recombinant congenic strains (RCS) constitute a set of inbred strains which are designed to dissect the genetic control of multigenic traits, such as tumour susceptibility or disease resistance. Each RCS contains a small fraction of the genome of a common donor strain, while the majority of genes stem from a common background strain. We tested at two stages of the inbreeding process in 20 RCS, derived from BALB/cHeA and STS/A, to see whether alleles from the STS/A donor strain are distributed over the RCS in a ratio as would theoretically be expected. Four marker genes (Pep-3; Pgm-1; Gpi-1 and Es-3) located at 4 different chromosomes were selected and the allelic distribution was tested after 3-4 and after 12 generations of inbreeding. The data obtained do not significantly deviate from the expected pattern, thus supporting the validity of the concept of RCS. PMID- 1921314 TI - Why modification of the LD50 test will not be enough. AB - During the last 10 years, the 'Three Rs' (reduction, refinement and replacement) concept of alternatives has come to be widely accepted, and new national and international laws require that non-animal procedures should replace animal experimentation wherever possible. Some reduction and refinement of animal use in toxicity testing has been achieved, and non-animal methods are becoming widely used as prescreens. However, even replacing the LD50 test by a modified and validated animal test, the Fixed Dose Procedure, will be a major achievement. In this paper it is argued that this is not good enough, and that more effort must be put into the development, validation, acceptance and use of genuine replacement alternative tests. PMID- 1921315 TI - Genetic variation within and between lines of diabetes-prone and non-diabetes prone BB rats; allele distribution of 8 protein markers. AB - Twenty-four inbred and 2 outbred lines of the BB rat have been genetically characterized by establishing the allele distribution of 8 monogenic protein markers. The marker genes are: plasma alkaline phosphatase-1 (Alp-1), catalase-1 (Cs-1), carboxylesterases (Es-1, Es-2, Es-14), glyoxalase I (Glo-1), group specific component (Gc), and haemoglobin-beta-chain (Hbb). At least 3 linkage groups are represented by this set of markers. Genetic variation was found both within and between lines. Within-line variation was observed in 4 lines, including the 2 outbred lines. The other 22 lines could be subdivided into 4 groups, each representing a unique allele distribution pattern. PMID- 1921316 TI - A simple device for the objective measurement of activity. AB - The activity of small experimental animals is difficult to quantify without prolonged observation and note-taking. We describe a relatively cheap and easily constructed device for monitoring and recording activity. Appropriate modifications make the basic device suitable for limited field applications. PMID- 1921317 TI - Ontogeny of absence-like and tonic seizures in the spontaneously epileptic rat. AB - The ontogeny of epileptic seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) was studied by examining behaviour and electroencephalogram (EEG) simultaneously. Weight gain and survival time were also studied. Compared with the control Kyo:Wistar rats, SER showed a much smaller increase in body weight. All male and female SER died before 20 and 18 weeks of age, respectively. Body tremor was observed at 2 weeks of age but disappeared after 11 weeks. Staggering gait appeared after 7 weeks of age, and intensified with age. Absence-like seizures characterized by paroxysmal appearance of 5-7 Hz spike-wave-like complexes were observed in the cortical or hippocampal EEG after 5 weeks of age, and tonic seizures with low voltage fast waves were observed after 6 weeks of age. All SER exhibited both absence-like and tonic seizures with high frequencies from 12 weeks of age. Differences with other spontaneous rat models of epilepsy and application methods for estimating seizure-inhibitory effects of anti epileptic drugs are discussed. PMID- 1921318 TI - A bone biopsy procedure for neonatal pigs. AB - Neonatal pigs were used to develop a surgical biopsy procedure to remove bone tissue from the ilium of small animals, with potential application for infants and small children. While the neonatal pig was under general anaesthesia, a scalpel was used to make a punch incision down to the ilium. Then a Craig Biopsy Trephine was used to remove a core sample of the bone. The samples ranged from 5 to 15 mm in length and 2 to 3 mm in diameter, with an average dry weight of 34.4 mg. The samples were adequate for mineral (calcium and zinc) analysis in our laboratory and may be equally suitable for histological or biochemical analyses. Surgical trauma was minimal, which permitted each pig to be biopsied every 7 days for 5 weeks without adverse consequences. PMID- 1921319 TI - A case of multiloculated, intracranial epidermoid cyst in a beagle dog. AB - An intracranial epidermoid cyst was identified within the fourth ventricle of a male 10-month-old beagle dog. The cyst, which exhibited a multilocular structure, was lined by a stratified squamous epithelium and filled with desquamated keratin. In the region of the roof of the fourth ventricle, choroid plexus adherent to the cyst wall and secondary compression of the cerebellum were also seen. PMID- 1921320 TI - Stability of pathogenic bacteria from laboratory animals in various transport media. AB - The stability of pathogenic bacteria from laboratory animals was investigated in various transport media at different temperatures. Bordetella bronchiseptica and Salmonella typhimurium survived for 8 days in phosphate-buffered saline (PBS, pH 7.0) at 37, 24, 4 and -20 degrees C; Brucella canis at 24, 4 and -20 degrees C; Corynebacterium kutscheri at 4 and -20 degrees C; and Pseudomonas aeruginosa at all but -20 degrees C. A marked decrease in numbers of Pasteurella multocida and Past. pneumotropica was observed in PBS at all temperatures. Skimmed milk in PBS improved the survival of Pasteurella spp. and Ps. aeruginosa at -20 degrees C. Neither glycerin, ascorbic acid nor sodium thioglycollate improved survival. The numbers of viable B. canis, Ps. aeruginosa and S. typhimurium were maintained in blood or faecal specimens held for 8 days at 4 degrees C. These results indicated that transport in PBS at 4 degrees C was the only method satisfactory for all species of pathogenic organisms tested, but Pasteurella spp. were the most difficult to maintain. PMID- 1921321 TI - Age of pairing affects reproduction in prairie voles. AB - The effect of the age at pairing on reproduction of weanling prairie voles was studied. The proportion of pairs producing a litter within 60 days was influenced significantly by the age at pairing. More voles paired at 31 days of age produced litters than those paired at 21 days of age. Assuming a gestation interval of 21 days, the earliest mating occurred around 33 days of age in both groups. On average, successful matings did not occur until voles were housed together for 2 to 3 weeks. No other measured variables were affected by age of pairing. PMID- 1921322 TI - Naturally acquired Pasteurella multocida subsp. multocida infection in a closed colony of rabbits: characteristics of isolates. AB - Twelve litters, comprising 41 rabbits aged 35 to 60 days old, in a closed university colony, were monitored for acquisition of nasal Pasteurella multocida subsp. multocida infection. Isolates from 11 infected rabbits were characterized by colonial morphology, capsular type, biotype and antibiotic resistance. Selected isolates were further characterized by somatic antigen typing. Two major strains of P. multocida subsp. multocida were detected in the colony. One strain had mucoid colonies, fermented few carbohydrates and was serotype A:5, whereas, the other strain had smooth iridescent colonies, non-typeable capsular antigen, type 3 somatic antigen and fermented more than twice as many carbohydrates. PMID- 1921324 TI - The effects of diet on the incidence of periodontitis in rats. AB - Four groups of 60 male Alpk:APfSD rats were fed different nutritionally comparable diets for 107 weeks with interim sacrifices at 26, 53 and 77 weeks in order to compare the effect of diet on the incidence of oral disease. Changes in the oral and nasal cavities were assessed by histopathology. Oro-nasal fistulation and severe periodontitis were associated with diets containing fibres originating from oats and barley. An expanded ground diet induced the most severe lesions. Aspects of the pathogenesis of the lesions observed are discussed. PMID- 1921323 TI - Morphometrical changes in the apical surface of the colonic absorptive cells in perinatal rats with special reference to the effect of fetal oral administration of milk in utero. AB - Perinatal changes in the apical surface of the colonic absorptive cells in the rat were studied morphometrically. Cell microvilli length increased from day 20 through neonatal day 3, during which a maximum incremental growth rate was noted between fetal day 22 and neonatal day 1. Microvilli width remained almost constant throughout the period. Enlargement of the apical surface of the microvilli showed a similar developmental pattern as was seen from the measurement of length and surface area of any one of the microvilli. Fetal oral administration of milk in utero caused incremental growth in length and surface area, as well as an associated apical surface enlargement. The present study indicates that the function of the colonic absorptive cells, which is acquired later on in utero, is activated by ingestion of maternal milk after birth. PMID- 1921325 TI - A percutaneous liver biopsy technique in ducks (Anas platyrhynchos) experimentally infected with duck hepatitis B virus. AB - Aylesbury ducks (Anas platyrhynchos) chronically infected with the duck hepatitis B virus provide a useful model for studying hepadna-virus infection, replication and the effects of antiviral therapy. In these studies, it is necessary to have an effective method for obtaining repeat liver specimens for histological and molecular analyses. We have therefore developed a percutaneous liver biopsy technique which has a low rate of complications, can be performed at repeated intervals, and provides sufficient quantities of liver tissue for histological and nucleic acid hybridization analysis. PMID- 1921326 TI - Phosphorus-induced nephrocalcinosis in female rats: a study on regression and clinical abnormalities. AB - The question addressed was whether preestablished phosphorus (P)-induced nephrocalcinosis would regress after dietary P restriction. Female rats were fed purified diets containing either 0.2% (w/w) P (low P) or 0.6% P (high P). After 29 days, the high-P diet had caused massive nephrocalcinosis as demonstrated chemically (by the analysis of calcium in kidney) and histologically (by inspection of kidney sections stained for calcium phosphate deposits). Switching rats from the high P to the low P diet did not result in a decrease in the degree of nephrocalcinosis within 91 days. Thus, P-induced nephrocalcinosis may not regress upon subsequent P restriction. Rats that had been fed either the 0.2 or 0.6% P diet for 56 days were examined clinically with respect to 14 selected variables. None of the variables discriminated between rats with or without nephrocalcinosis. This might imply that P-induced nephrocalcinosis in female rats does not cause significant discomfort. PMID- 1921327 TI - Population distribution profiles of the activities of blood alanine and aspartate aminotransferase in the normal F344 inbred rat by age and sex. AB - Data on the blood enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were collected from control male and female F344 rats participating in toxicity studies at 17, 30, 56, 80 and 106 weeks of age. The data were skewed to the right with significant deviation from normality. Applying the Box-Cox transformation, it was concluded that approximately normal distributions could be obtained by using the reciprocal transformation. In general, the males showed a greater degree of heterogeneity for both enzymes. Enzyme activities at 17 weeks were lowest for both ALT and AST. There was a high correlation between the activities of blood ALT and AST, with some animals showing dramatic transient increases. Significant differences among studies with respect to the enzyme activities in rats of the same age were demonstrated. PMID- 1921328 TI - Aqueous lithium heparin is a superior anticoagulant to solid heparin for blood collection from the retro-orbital sinus of rats. AB - Blood specimens from the retro-orbital sinus of 80 Sprague Dawley rats were collected into tubes containing lithium heparin either as a solid or an aqueous solution. Plasma was separated for blood chemistry analysis. Twenty-eight blood specimens collected into tubes containing solid heparin were clotted and eight specimens were partially clotted making these samples unsuitable for some analyses. None of the specimens collected into heparin solution showed any evidence of clotting. The variances of lactate dehydrogenase and alpha hydroxybutyrate dehydrogenase activities in plasma prepared with solid heparin were significantly greater than those prepared with heparin solution. Lithium heparin solution is now used routinely in our laboratory. PMID- 1921329 TI - C1 inhibitor deficiency: molecular and immunologic basis of hereditary and acquired angioedema. PMID- 1921330 TI - Thymus in simian immunodeficiency virus-infected rhesus monkeys. AB - The thymuses from 20 simian immunodeficiency virus (SIV)-infected and 4 uninfected rhesus monkeys were examined at intervals after infection to determine whether there were specific SIV-induced lesions, to document the serial distribution of SIV antigens, mRNA, and DNA, to quantitate the number of infected cells, and to correlate thymic changes with other parameters of infection. The following techniques were used: gross pathology, histopathology, immunohistochemistry, electron microscopy, in situ hybridization, polymerase chain reaction, and limiting dilution culture. Thymic involution due to loss of lymphocytes was apparent 8 weeks after inoculation. No epithelial damage or loss of Hassall's corpuscles was observed. Culture was the most sensitive technique for detecting SIV, being positive in 19 of 20 inoculated monkeys. The polymerase chain reaction was negative in one thymus that was positive at a low level by culture. In situ hybridization was positive in 14 of 19 thymuses examined, with a few macrophages in the cortex having a strong signal and numerous lymphocytes in the medulla having a weak signal. Mature viral particles and viral budding could not be demonstrated by electron microscopy. The number of cells positive for viral RNA by in situ hybridization correlated with the level of serum antigenemia. These observations suggest that thymic macrophages and lymphocytes are infected with SIV within 2 weeks after inoculation. SIV apparently directly causes loss of thymic lymphocytes and immunodeficiency without infecting or damaging the thymic epithelium. No specific SIV-induced lesions were recognized. The number of cells in the thymic medulla expressing SIV RNA correlates with the level of serum antigen, which has been previously shown to be correlated with disease progression. PMID- 1921331 TI - Paraneoplastic anti-Purkinje and type I anti-neuronal nuclear autoantibodies bind selectively to central, peripheral, and autonomic nervous system cells. AB - Autoantibodies provide serologic markers for subacute cerebellar degeneration in the setting of gynecologic or breast cancer (anti-Purkinje cell cytoplasmic antibodies, PCAb), and for encephalomyeloradiculoneuropathies in the setting of small cell lung carcinoma (type I anti-neuronal nuclear antibodies, ANNA-I). PCAb and ANNA-I are not species-restricted in their specificities. The subject of this report is a systematic immunocytochemical investigation of the distribution and types of cells in the mouse central and peripheral nervous system that bind these IgG autoantibodies. Sera used for the study were from two patients with prototypic PCAb reactivity and two with prototypic ANNA-I reactivity, none of whom had evidence of other autoantibodies, and from four age- and sex-matched healthy control subjects. The patients' clinical features were consistent with the classic syndromes that have been reported with PCAb and ANNA-I, respectively. PCAb bound prominently to the cytoplasm of cerebellar Purkinje cells, and also to other large cytoplasm-rich neurons throughout the central nervous system, to neurons in sensory and sympathetic ganglia and myenteric plexus, and to cells of the adrenal medulla. ANNA-I, on the other hand, bound to virtually all neurons in the central and peripheral nervous system, including sensory and autonomic ganglia, myenteric plexus and cells of the adrenal medulla. An unanticipated finding was that immunoreactivity with ANNA-I was enhanced by fixing tissues briefly with formalin. Astrocyte processes were stained by PCAb and by ANNA-I (but not by the control sera). The cytoplasm of sciatic nerve Schwann cells was stained strikingly by PCAb, but ANNA-I did not bind to Schwann cells. Although it has not yet been determined whether or not PCAb or ANNA-I per se are pathogenic, it is apparent that they represent at least a component of an immune response that is initiated by tumor antigens. The distribution of these tumor-related antigens in the nervous system is consistent with the diversity of neurologic manifestations that can occur in individual patients with the associated paraneoplastic syndromes. PMID- 1921332 TI - Allotransplantation of K248 feline mammary carcinoma cell line in cats. A model for monoclonal antibody guided detection and therapy of human breast cancer. AB - In response to the need for appropriate models for monoclonal antibody guided detection and therapy of human breast cancer, we developed an allogeneic host tumor model by injecting K248C and K248P cells into cats. A comparison between the K248C- and K248P-induced tumors with respect to biological behavior and histological appearance was made throughout the study. Allotransplantation of tumor cells was performed both in newborn cats and fetal cats between days 42 and 51 of gestation, but only tumor cells injected by the latter approach resulted in tumor growth in all animals injected. Both tumor cell lines gave rise to progressively growing tumors at the site of injection, metastatic spread of tumor cells to various organs, and death from progression 2-4 months after birth. The predominant histological appearance of the K248C and K248P allografts resembled the cribriform and tubulo-papillary growth patterns, respectively, of the original tumor from which the two cell lines were derived. Autopsy of 1-day kittens showed that metastasis started already in the fetus in the short period between injection of tumor cells and birth. Three predominant patterns of metastases were identified: the pulmonary/pleural type, the abdominal type, and the soft tissue type. A lower incidence of metastases was found in bones and brain. The K248C allografts formed significantly more metastases of the abdominal type than K248P tumors (p less than 0.05). No difference in survival was observed between animals with K248C or K248P allografts. The difference in take rate and latency period between K248C and K248P in athymic mice does not seem to be present in the feline host. The similarity of the present model to spontaneous feline and human mammary carcinoma is discussed. PMID- 1921333 TI - Role of laminin in localization of human dermal mast cells. AB - Human connective tissue type mast cells (CTMC) are frequently located in close proximity to microvascular and neural basement membranes (BM). We have explored the interaction between human dermal connective tissue-type (chymase positive) mast cells and laminin, a component of BM. In this report, we document that normal CTMC express laminin receptors and are intimately associated with laminin of BM in vivo and pericellular laminin complexes in vitro. Upon degranulation in vitro, CTMC-laminin complexes dissociate and CTMC do not adhere to laminin substrates. In cutaneous mastocytosis/urticaria pigmentosa, CTMC do not express laminin receptors detectable by immunohistochemistry, and are frequently not in close association with laminin of vascular BM. These same features could be induced by degranulation of normal mast cells in organ culture. These findings indicate that CTMC-laminin interactions may be important determinants of mast cell localization in tissue compartments. PMID- 1921334 TI - Extracellular matrix biosynthesis by cultured fetal rat lung epithelial cells. IV. Effects of chronic exposure to retinoic acid on growth, differentiation, and collagen biosynthesis. AB - Effects of chronic exposure to retinoic acid on a cell line (FRLE cells) established from the fetal rat lung type II alveolar epithelial cell have been studied. Chronic exposure to retinoic acid inhibited proliferation and altered the pattern of culture morphology at the light microscopic level. At the ultrastructural level, the development of lamellar body-like structures was inhibited. Although the rates of both total collagen and protein produced per cell were enhanced by chronic retinoic acid exposure, the increase in collagen production exceeded that of total protein synthesis. Chromatographic evaluation of collagen types I, III, IV, and V revealed increases in the amounts of radioactivity incorporated into each collagen type. However, the magnitudes of the increases differed for each collagen type, with the production of type IV collagen being the most enhanced. These analyses also indicated several additional effects on collagen production: 1) collagen type specific alterations in the ratio of secreted to cell associated molecules, 2) an increased ratio of type I homotrimers to type I heterotrimers, and 3) a decreased ratio of type V homotrimers to type V heterotrimers. These results indicate that chronic exposure to retinoic acid selectively affects collagen production in and differentiation of FRLE cells and establish that these changes are opposite to those observed under conditions of chronic exposure to EGF. PMID- 1921335 TI - Phenotypic features of smooth muscle cells during the evolution of experimental carotid artery intimal thickening. Biochemical and morphologic studies. AB - Balloon catheter denudation of rat carotid artery that results in significant medial damage is followed by marked intimal smooth muscle cell (SMC) proliferation associated with limited endothelial regrowth. In this report we demonstrate that: (a) SMC of the carotid media, preceding their intimal proliferation, develop a cytoskeletal profile and morphology consistent with a de differentiated SMC phenotype; and (b) both medial and intimal SMC subsequently revert to a cytoskeletal profile and morphology reflecting incomplete but significant re-differentiation toward normal SMC phenotype. Specifically, early after balloon injury, SMC of the media and those that have migrated into the intima contain decreased amounts of actin, desmin, and tropomyosin and increased amounts of vimentin; moreover, beta-actin becomes the dominant actin isoform, whereas alpha-actin decreases as compared with that found in normal medial SMC. Late after balloon injury, actin is still less abundant, however, desmin, tropomyosin, and vimentin return toward normal values and both medial and intimal SMC again show a predominance of alpha-actin, although the endothelium does not regenerate over the central surface of intimal thickening in this model. The SMC surface to volume ratio significantly decreases early after balloon injury, whereas it is not significantly different late after balloon injury as compared with that of SMC of the normal carotid media. We demonstrate, furthermore that: (c) adjacent luminal SMC are interconnected by gap junctions and develop focal tight junctions, a feature not reported previously to occur in smooth muscle; these cells however do not form any well defined membrane specialization with the leading edge of endothelium, supporting the view that presence of modified SMC on the luminal surface of chronically denuded vessels is not responsible for the cessation of endothelial regrowth. PMID- 1921336 TI - Haematological changes in house painters using epoxy paints. AB - Haematological parameters, iso-transferrin ratio in plasma and serotonin uptake in platelets were studied in 10 men (age range 21-54 years) with occupational long-term, low level exposure to vapours from epoxy paints. The control group consisted of 10 healthy men (age range 20-48 years) not occupationally exposed to chemicals or organic solvents. The mean cellular volume of erythrocytes was significantly higher for the house painters than the controls (p less than 0.05). The plasma concentration of iso-transferrin with isoelectric point 5.7 (Tf5.7) and the ratio between Tf5.7 and total transferrin (Tftot) were significantly higher in the exposed group (p less than 0.05). The uptake of serotonin in platelets (Vmax) from the exposed workers was significantly lower than the values for the controls (p less than 0.01). The results indicate an association between the observed biological effects and the chemical exposure, and we speculate that this is caused by changes in structure and function of the cell membranes. PMID- 1921337 TI - Environmental and biological monitoring of workers exposed to inorganic lead. AB - A total of 20 workers who were exposed to inorganic lead in two local firms (M and N) were studied. Lead concentrations in the air (PbA) at firm M exceeded the threshold limit value (TLV) of 0.150 mg/m3 established by Spanish and EC legislation, while atmospheric lead at firm N exceeded the action level of 0.075 mg/m3. In the same population, biological exposure indices (BEI) were also determined; these included lead in whole blood (PbB), erythrocyte activity of aminolevulinic acid (ALA-D), urinary excretion of aminolevulinic acid (ALA-U) and zinc protoporphyrin (ZPP). The relationship between the exposure parameters (PbA, PbB) and the biological activity indices (ALA-D, ALA-U, ZPP) were analysed statistically in order to obtain levels of significance, coefficients of correlation and regression equations. The high coefficients of correlation found confirm the usefulness of BEI in evaluating exposure to lead fumes and lead dust. PMID- 1921338 TI - A cross-sectional study of health complaints among 79 data entry operators using video display terminals. AB - This paper reports on the findings of a cross-sectional study of 79 data entry clerks employed by an Ontario-based organization in five separate offices. The study was conducted to identify factors associated with physical complaints experienced by these office workers. A large percentage of the data entry clerks reported chronic physical complaints (eyestrain, musculo-skeletal pains, headache) as well as emotional or mental stress which they felt were associated with their occupation. Poorly designed overhead lighting systems in all offices contributed to both eyestrain and headache. Duration of employment as a data entry operator within the organization was not associated with stress or physical health complaints. The presence of an adjustable workstation did not in itself guarantee any protection from these conditions. Highly significant associations between occupational stress levels and some physical complaints were observed. The presence of these associations indicated that the management of both physical and stress complaints within these office environments should be tackled simultaneously. PMID- 1921339 TI - Absence from work due to treatment for genital warts. AB - An audit was undertaken of time lost from work and reasons given to employers for absence in a group of patients attending a city centre outpatients department. For the audit a Department of Genito-urinary Medicine was selected and 54 patients were interviewed. The time lost by attendance and the reasons given are discussed as are ways of improving medical care through new treatments and altered appointment times. PMID- 1921340 TI - Sickness absence and control of insulin-treated diabetes as assessed by glycosylated haemoglobin. AB - The sickness absence records for 1986 were obtained for 63 employed insulin treated diabetic patients who had glycosylated haemoglobin (HbA1) measurements during that year. One subject whose absence was associated with attempts to improve control because of pregnancy was excluded from the analysis. Fifteen had good control (HbA1 8.5 per cent or less) and 47 had poor control (HbA1 greater than 8.5%). The groups were similar for age, sex, duration of diabetes and occupation. The distribution of sickness absence showed greater frequency of absence (p less than 0.05), greater number of working days lost (p less than 0.02), and greater average duration of absence (p less than 0.04) among those diabetic workers with poor control compared to those with good control. Because some individuals with poor control had no absence, HbA1 measurement cannot be recommended on its own to identify those workers who will be absent from work. Its use may lie in indicating a level below which sickness absence is minimized. PMID- 1921341 TI - Human nail dust: hazard to chiropodists or merely nuisance? AB - This survey was carried out in response to anxiety among chiropodists as earlier reports had raised the possibility of respiratory damage as a result of sensitization to trichophytons. Questionnaires were sent to 327 chiropodists and 168 replies were received. The aim was to investigate respiratory symptoms and their relationship to work and drill usage. All of those completing questionnaires were invited to attend the occupational health department for prick tests and lung function tests. Just over one half of those who were invited attended. Although upper respiratory symptoms were common, only eye symptoms and wheeze were significantly more prevalent in those who used non-vacuum drills. Nasal symptoms were commoner in those who had spent less than ten years in the profession. Throat symptoms and multiple symptoms occurred more commonly in the 17 per cent of attenders who had positive prick tests to trichophytons. There were no cases of occupational asthma and no definite relationship between any symptom and work. It was confirmed that sensitization to trichophytons was common (16.5 per cent) but did not produce chest problems. Nail dust might produce symptoms by simple irritation of the upper respiratory tract. PMID- 1921342 TI - Screening for coronary risk factors in occupational health practice. AB - Screening for coronary risk factors (blood cholesterol greater than 5.2 mmol/l; body mass index greater than 25; blood pressure greater than 140/90 and positive smoking history) using nurse administered voluntary health assessments was studied in occupational health practice. A high employee participation rate (80.9 per cent) was achieved with few employees declining to attend, confirming the advantages of workplace based screening. Hypercholesterolaemia, overweight and smoking were the most prevalent risk factors. Men had higher rates than women as judged by independent or concomitant risk factor rates; 56.5 per cent of men were over ideal body weight, 40 per cent of men smoked, 35.7 per cent of men had two risk factors and 2 per cent of men had four risk factors. Blood cholesterol and blood pressure were shown to increase with increasing body weight. It is suggested that body weight reduction and smoking cessation are the preferred intervention strategies in occupational health practice. PMID- 1921343 TI - Byssinosis in the cotton waste industry. AB - A cross-sectional survey was carried out on 772 workers in 27 mills in the North of England involved in the processing of cotton waste. The overall prevalence of byssinosis as defined by Schilling's criteria was 9.8 per cent with 5.4 per cent having grades 2 and 3. The prevalence in workers who had only ever had cotton waste exposure (5 per cent) was significantly less than for those who had mixed waste and raw cotton exposure. There was no clear relationship between prevalence of byssinosis and years of exposure or dust levels. PMID- 1921344 TI - Aspects of occupational health in the sugar cane industry. AB - Workers in developing countries face as many, if not more, work-related health problems as their counterparts in industrialized nations. This paper concentrates on occupational health problems in the sugar industry, which exists in 40 countries, mostly in the Third World. Sugar cane workers have a high level of occupational accidents and are exposed to the high toxicity of pesticides. They may also have an increased risk of lung cancer, possibly mesothelioma. This may be related to the practice of burning foliage at the time of cane-cutting. Bagassosis is also a problem specific to the industry as it may follow exposure to bagasse (a by-product of sugar cane). The workers may also be affected by chronic infections which reduce their productivity. The legal framework for their protection is often inadequate. In conclusion, areas of future research are suggested. PMID- 1921345 TI - Death certificate categorization of malignant pleural and peritoneal mesothelioma in a cohort of asbestos insulation workers. AB - Accuracy of diagnosis of malignant mesothelioma (pleural and peritoneal) was studied in a cohort of asbestos insulation workers in the United States and Canada. Initial clinical diagnosis, clinical diagnosis at death and death certificate diagnosis were compared with the diagnosis of malignant mesothelioma ascertained by full data review at the Division of Environmental and Occupational Medicine, Mount Sinai Medical Center, New York ('best evidence'). In both groups the death certificate diagnosis was somewhat less frequently accurate than clinical diagnosis at death. Knowledge of the patients' occupational history by the attending physician and its relation to accuracy of diagnosis of malignant mesothelioma is considered. PMID- 1921346 TI - Asthma in silk workers. AB - Workers who process raw silk are exposed to a fine dust derived from the gum that binds the strands secreted by the silkworm. Fifty-three such workers, all women and non-smokers with an average of 5.8 years of service in the industry, were examined. Eighteen (33.9 per cent) workers had occupational asthma, the highest proportion (48.2 per cent) being in those twisting silk. A lower prevalence (20.0 per cent) was found in workers in the degumming sector, while the least (16.6 per cent) was in weavers. This declining prevalence in the three processing stages appears to be in line with their declining exposure to dust. The occupational asthma was of the intermediate and late types occurring 30 minutes to 6 hours after starting work and subsiding 1 to 8 hours after leaving the factory. PMID- 1921347 TI - Harmonization of training. PMID- 1921348 TI - Viewpoint '91 (J. Soc. Occup. Med. 1991;41:5-6). PMID- 1921349 TI - Santayana's warning. PMID- 1921350 TI - A triphasic theory for the swelling and deformation behaviors of articular cartilage. AB - Swelling of articular cartilage depends on its fixed charge density and distribution, the stiffness of its collagen-proteoglycan matrix, and the ion concentrations in the interstitium. A theory for a tertiary mixture has been developed, including the two fluid-solid phases (biphasic), and an ion phase, representing cation and anion of a single salt, to describe the deformation and stress fields for cartilage under chemical and/or mechanical loads. This triphasic theory combines the physico-chemical theory for ionic and polyionic (proteoglycan) solutions with the biphasic theory for cartilage. The present model assumes the fixed charge groups to remain unchanged, and that the counter ions are the cations of a single-salt of the bathing solution. The momentum equation for the neutral salt and for the intersitial water are expressed in terms of their chemical potentials whose gradients are the driving forces for their movements. These chemical potentials depend on fluid pressure p, salt concentration c, solid matrix dilatation e and fixed charge density cF. For a uni uni valent salt such as NaCl, they are given by mu i = mu io + (RT/Mi)ln[gamma 2 +/- c(c + cF)] and mu w = mu wo + [p-RT phi (2c + cF) + Bwe]/pwT, where R, T, Mi, gamma +/-, phi, pwT and Bw are universal gas constant, absolute temperature, molecular weight, mean activity coefficient of salt, osmotic coefficient, true density of water, and a coupling material coefficient, respectively. For infinitesimal strains and material isotropy, the stress-strain relationship for the total mixture stress is sigma = - pI-TcI + lambda s(trE)I + 2 musE, where E is the strain tensor and (lambda s, mu s) are the Lame constants of the elastic solid matrix. The chemical-expansion stress (-Tc) derives from the charge-to charge repulsive forces within the solid matrix. This theory can be applied to both equilibrium and non-equilibrium problems. For equilibrium free swelling problems, the theory yields the well known Donnan equilibrium ion distribution and osmotic pressure equations, along with an analytical expression for the "pre stress" in the solid matrix. For the confined-compression swelling problem, it predicts that the applied compressive stress is shared by three load support mechanisms: 1) the Donnan osmotic pressure; 2) the chemical-expansion stress; and 3) the solid matrix elastic stress. Numerical calculations have been made, based on a set of equilibrium free-swelling and confined-compression data, to assess the relative contribution of each mechanism to load support. Our results show that all three mechanisms are important in determining the overall compressive stiffness of cartilage. PMID- 1921351 TI - Stiffening of the femoral head due to inter-trabecular fluid and intraosseous pressure. AB - The mechanical properties of cancellous bone, as measured from bone plug samples have been widely documented. However, few tests have been attempted to explore the effects the intertrabecular contents may have on the load bearing capabilities. In this study, canine femoral heads were subjected to dynamic compressive strain cycles. The femoral heads were tested intact, as well as with disrupted boundary conditions of the continuous, intraosseous fluid space. A significant reduction in mechanical stiffness was observed when the fluid compartment boundary was disrupted by drilling a hole part way into the femoral neck. A finite element model of a typical femoral head showed that the stiffness change was not due to removal of material from the neck, hydraulic effects notwithstanding. Refilling the hole in the neck with saline solution and sealing the boundary restored the stiffness to the intact baseline level. However, an increase in the fluid pressure did not cause a statistically significant increase in the stiffness of the femoral head. PMID- 1921352 TI - Ligament-bone interaction in a three-dimensional model of the knee. AB - In mathematical knee-joint models, the ligaments are usually represented by straight-line elements, connecting the insertions of the femur and tibia. Such a model may not be valid if a ligament is bent in its course over bony-surfaces, particularly not if the resulting redirection of the ligament force has a considerable effect on the laxity or motion characteristics of the knee-joint model. In the present study, a model for wrapping of a ligament around bone was incorporated in a three-dimensional mathematical model of the human knee. The bony edge was described by a curved line on which the contact point of the line element representing a ligament bundle was located. Frictionless contact between the ligament bundle and the bone was assumed. This model was applied to the medial collateral ligament (MCL) interacting with the bony edge of the tibia. It was found that, in comparison with the original model without bony interactions, the bony edge redirected the ligament force of the MCL in such a way that it counterbalanced valgus moments on the tibia more effectively. The effect of the bony interaction with the MCL on the internal-external rotation laxity, however, was negligible. PMID- 1921353 TI - New mathematical definition and calculation of axial rotation of anatomical joints. AB - In the field of joint kinematics, clinical terms such as internal-external, or medical-lateral, rotations are commonly used to express the rotation of a body segment about its own long axis. However, these terms are not defined in a strict mathematical sense. In this paper, a new mathematical definition of axial rotation is proposed and methods to calculate it from the measured Euler angles are given. The definition and methods to calculate it from the measured Euler angles are given. The definition is based on the integration of the component of the angular velocity vector projected onto the long axis of the body segment. First, the absolute axial rotation of a body segment with respect to the stationary coordinate system is defined. This definition is then generalized to give the relative axial rotation of one body segment with respect to the other body segment where the two segments are moving in the three-dimensional space. The well-known Codman's paradox is cited as an example to make clear the difference between the definition so far proposed by other researchers and the new one. PMID- 1921354 TI - Human head dynamic response to side impact by finite element modeling. AB - The dynamic response of the human head to side impact was studied by 2 dimensional finite element modeling. Three models were formulated in this study. Model I is an axisymmetric model. It simulated closed shell impact of the human head, and consisted of a single-layered spherical shell filled wiht an inviscid fluid. The other two models (Model II and III) are plane strain models of a coronal section of the human head. Model II approximated a 50th percentile male head by an outer layer to simulate cranial bone and an inviscid interior core to simulate the intracranial contents. The configuration of Model III is the same as Model II but more detailed anatomical features of the head interior were added, such as, cerebral spinal fluid (CSF); falx cerebri, dura, and tentorium. Linear elastic material properties were assigned to all three models. All three models were loaded by a triangular pulse with a peak pressure of 40 kPa, effectively producing a peak force of 1954 N (440 lb). The purpose of this study was to determine the effects of the membranes and that of the mechanical properties of the skull, brain, and membrane on the dynamic response of the brain during side impact, and to compare the pressure distributions from the plane strain model with the axisymmetric model. A parametric study was conducted on Model II to characterize fully its response to impact under various conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921355 TI - The effects of external bending moments on lumbar muscle force distribution. AB - A detailed biomechanical model of the low-back musculature that predicts muscle force distribution in response to external loading is presented. The paper shows that the class of loading tasks that involve an erect posture and an arbitrary load placed on the upper limbs can be described as a loading plane whose axes are the flexion and lateral bending moments. Under these conditions, the individual muscle forces are described as a three-dimensional surface defined by the loading plane and termed the muscle activity surface (MAS). The MAS and the loading plane intersect along the switching curve which separates the load combinations that activate the muscle from those that do not. The paper suggests the existence of a recruitment order of low back muscles in response to external loads and presents a comprehensive framework for examining earlier studies that used EMG measurements to validate physiological and mechanical predictions. PMID- 1921356 TI - Biaxial testing of membrane biomaterials: testing equipment and procedures. AB - A testing facility for measuring the biaxial mechanical properties of highly deformable membranes is described. Forces are applied, via strain-gauge force transducers, to four points on each side of an initially square 12 to 25 mm membrane sample to produce biaxial extensions of up to 80 percent of undeformed length. Strain is estimated from the displacement of markers bounding a 1 to 2 mm central square. The accuracy of stress and strain field measurements has been assessed by finite element analysis of a biaxially-loaded isotropic elastic membrane. Major advantages of the present system over those previously described in the literature are that 1) sample mounting procedures are simplified, 2) there is provision for independent adjustment of stress field uniformity and measurement of the applied point forces and 3) faster strain rates can be imposed on the relatively small samples tested. PMID- 1921357 TI - Microscopic instrumentation and analysis of laser-tissue interaction in a skin flap model. AB - A dorsal skin flap model for microcirculatory studies has been modified for "in vivo" studies of laser-tissue interaction with microcirculation. An experimental apparatus has been built implementing a laser delivery system, video microscopy during irradiation, and thermal recordings. This model has been used to study irradiation effects on microcirculation using the argon laser (488 and 514.5 nm) and the argon pumped dye laser at 577 nm. The results include: measurements of the optical properties of the model; dosimetry measurements for the production of embolized and stationary coaguli in arterioles and venules; and focal vessel disappearance of venules irradiated with the argon or the argon pumped dye laser at 577 nm; a method to determine light attenuation in the model; a unique method for measurements of blood flow velocity in arterioles and venules and measurements obtained with this method; measurements of transient and steady state temperatures during irradiation and a study of laser induced photorelaxation phenomena in venules. PMID- 1921358 TI - Convective heat transfer coefficients in the circulation. AB - Convective heat transfer in the vessels of the circulatory system is investigated numerically. In the modeling, account is taken of the non-Newtonian rheological properties of blood and the presence of a cell-depleted plasma layer at the vessel wall. The latter is found to produce a remarkable enhancement of the heat transfer rate in the small vessels, while the effects due to the rheological behavior of blood are comparatively low. A comparison with experimental data available in the open literature is finally attempted. PMID- 1921359 TI - A new view of convective-diffusive transport processes in the arterial intima. AB - In this paper a new theoretical framework is presented for analyzing the filtration and macromolecular convective-diffusive transport processes in the intimal region of an artery wall with widely dispersed macromolecular cellular leakage sites, as proposed in the leaky junction-cell turnover hypothesis of Weinbaum et al. In contrast to existing convection-diffusive models, which assume that the transport is either 1-D, or convection is primarily in a direction normal to the endothelial surface, the present model considers for the first time the nonuniform subendothelial pressure field that arises from the different hydraulic resistances of normal and leaky endothelial clefts and the special role of the internal elastic lamina (IEL) in modulating the horizontal transport of macromolecules after they have passed through the leaky clefts of cells that are either in mitosis or demonstrate IgG labeling. The new theory is able to quantitatively explain the growing body of recent experiments in which an unexpectedly rapid early-time growth of the leakage spot has been observed and the longer time asymptotic behavior in which the leakage spot appears to approach an equilibrium diameter. The new theory also predicts the observed doubling in macromolecular permeability between EBA labeled blue and white areas when the frequency of leakage sites is doubled. This frequency for doubling of permeability, however, is an order of magnitude smaller than predicted by the author's previous model, Tzeghai et al., in which only convection normal to the endothelial surface was considered and the pressure was uniform in the intima. The longer time model predictions are used to explain the time scale for the formation of liposomes in subendothelial tissue matrix in animal feeding experiments where it has been observed that the extracellular lipid concentration rises sharply prior to the entry of monocytes into the intima. PMID- 1921360 TI - Hemodynamics analysis of a stenosed carotid bifurcation and its plaque-mitigating design. AB - Considering transient two-dimensional laminar flow in a diseased carotid artery segment with realistic inlet and outflow conditions, detailed velocity profiles, pressure fields, wall shear stress distributions and coupled, localized plaque formations have been simulated. The type of outflow boundary condition influences to a certain degree the extent of plaque build-up, which in turn reduces "disturbed flow" phenomena such as flow separations, recirculation zones, and wavy flow patterns in the artery branches during portions of the pulse. Based on computer experiments varying key geometric factors, a plaque-mitigating design of a carotid artery bifurcation has been proposed. Elimination of the carotid bulb, a smaller bifurcation angle, lower area ratios, and smooth wall curvatures generated a design with favorable hemodynamics parameters, leading to reduced plaque build-up by factors of 10 and 2 in the internal carotid and in the external carotid, respectively. PMID- 1921361 TI - Separated flow demonstrated by digitized cineangiography compared with LDV. AB - In order to demonstrate separated flow in vivo, a method for the computerized analysis of cineangiographies has been developed, tested in vitro, and compared with LDV. A pulsatile flow was created in a glass model bifurcation, and velocity profiles were obtained with LDV at several phase angles. The flow was cinefilmed during contrast injection and the images were digitized. The computer then transformed the image sequence into parametric images representing arrival times of the contrast. The separation regions demonstrated with LDV were identified as areas with delayed contrast arrival. A preliminary analysis of a cineangiography in vivo is also included. PMID- 1921362 TI - Mechanically induced pendelluft flow in a model airway bifurcation during high frequency oscillation. AB - A single bifurcation with adjustable branch compliances, resistances and inertances was used to study the generation of pendelluft flows during ventilation at tidal volumes of 5-15 ml and frequencies of 6-26 Hz, corresponding to parent branch Reynolds numbers of 400-8000 and Womersley parameter values of 12-25. Pendelluft was quantified by the ratio of tidal volume sum in sibling branches to tidal volume in the parent branch. This tidal volume fraction being greater than one in all experiments where an asymmetry in branch mechanics was imposed, indicated that some degree of pendelluft was always present. Asymmetries in compliance and in inertance produced much greater pendelluft than an asymmetry in resistance. The largest tidal volume fraction, equal to 2.75, was recorded when inertance in both sibling branches was high, resistance was low, and compliances differed by a factor of five. Tidal volume fraction always peaked at an optimal frequency between 12-24 Hz, similar to the frequencies at which physiologic transport optima have previously been observed. PMID- 1921364 TI - Amelioration of renal ischemic injury by phosphocreatine. AB - Phosphocreatine (PCr) is a critical intracellular energy reservoir used in the regeneration of ATP. The aim of this study was to determine the efficacy of exogenously added PCr on preservation of renal function in an in vitro model. The renal artery and ureter of a rat were cannulated and the kidney was subjected to 45 min of normothermic in vivo ischemia. The kidneys were then perfused ex vivo with either a Krebs-bicarbonate solution (Krebs) or a Krebs solution containing 3 mM PCr or an osmotically balanced solution containing 3 mM PCr. Our results indicate that the perfusion of kidneys subjected to 45 min of warm ischemia with solutions containing PCr resulted in significant improvements in GFR, RPF, and V, FRNa and FRH2O compared to KREBS alone. This suggests that the important factor in preservation of kidney function after an initial ischemic insult may be the addition of PCr rather that the electrolyte solution used. PMID- 1921363 TI - Differentiation of human motion data using combined spline and least squares concepts. AB - A differentiation method, which combines the concepts of least squares and splines, has been developed to analyze human motion data. This data smoothing technique is not dependent on a choice of a cut-off frequency and yet it closely reflects the nature of the phenomenon. Two sets of published benchmark data were used to evaluate the new algorithm. PMID- 1921365 TI - Circadian rhythm in gastric mucosal blood flow in fasting rat stomach. AB - Circadian rhythms are present in several gastric functions including acid secretion and emptying rates. We hypothesize that aggressive and defensive factors in the gastric mucosa follow similar circadian rhythms. The purpose of this study was to determine if gastric mucosal blood flow, a known defensive factor, manifests a circadian rhythm in fasting rats. Ninety-six male Sprague Dawley rats were light-adapted in isolation chambers for 3 weeks prior to the study. Half the rats experienced light from 6:00 AM to 6:00 PM, the other half from 6:00 PM to 6:00 AM. After an 18-hr fast, 12 rats were studied at each of eight sampling times: 0100, 0400, 0700, 1000, 1300, 1600, 1900, and 2200 hr after lights on (HALO). After anesthesia and laparotomy, the stomachs were opened along the anterior surface, gently stretched with mucosal surface upmost, and trapped between two lucite rings, with blood supply intact. Mucosal blood flow (ml/min/100 g) was measured in the forestomach, corpus, and antrum with a laser Doppler flowmeter (TSI Laserflo BPM 403). Cosinor analysis showed a significant (P less than 0.01) circadian rhythm in gastric mucosal blood flow within the corpus and antrum, but not in the forestomach. Peak time for corpus blood flow was 21:45 +/- 0:56 HALO (3:45 AM). In the antrum it was 0:51 +/- 1:08 HALO (6:51 AM). These results support the hypothesis that circadian rhythms in mucosal defensive functions are an integral part of normal gastric physiology. PMID- 1921366 TI - Splanchnic blood flow response to intraaortic balloon pump assist of hemorrhagic shock. AB - Hemorrhagic shock results in marked changes in splanchnic arterial blood flow. We studied the effects of intraaortic balloon pump assist (IABP) upon splanchnic blood flow during sustained hemorrhagic shock and following volume resuscitation. Hemorrhagic shock was induced (mean blood pressure = 30 mm Hg) for 120 min in 20 dogs. Controls (n = 11) underwent resuscitation with shed blood and lactated Ringers solution only. In the study group (n = 9), IABP was begun after 60 min of hemorrhagic shock and continued throughout a 90-min period after resuscitation. Hemodynamic parameters were assessed and splanchnic blood flow was estimated (radioactive microsphere technique) at baseline, through 120 min of sustained hypotension, and during the resuscitation period. Splanchnic blood flow was significantly reduced in both the control and the IABP groups during the period of hemorrhagic shock. Interestingly, the IABP group was found to have a return to preshock splanchnic viscera perfusion without the hyperemic reperfusion phenomenon seen in control animals resuscitated with shed blood and Ringers lactate alone. IABP assist of hemorrhagic shock appears to improve vasomotor control of splanchnic blood flow in this experimental preparation of shock. This may result in less reperfusion injury to the splanchnic viscera during the resuscitation of severe hemorrhagic shock. PMID- 1921367 TI - Seventy-two-hour preservation of porcine liver by continuous hypothermic perfusion with UW solution in comparison with simple cold storage. AB - Porcine livers preserved for 72 hr using continuous hypothermic perfusion (CHP) were studied in order to compare the effects of CHP on energy metabolism with those of simple cold storage (SCS). The livers of the CHP group were perfused in situ for 72 hr at 7 degrees C with University of Wisconsin (UW) solution and FC 43 as an oxygen carrier, while those of the S1 group were stored ex situ for 48 hr at 4 degrees C in UW solution, and those of the S2 group for 72 hr. They were then recirculated with human blood at 37 degrees C for 2 hr for the evaluation of their viability. At the end of preservation, significantly higher levels of total adenine nucleotides (TAN) and energy charge (EC) were observed in the CHP group compared with the S1 and S2 groups. At 2 hr recirculation, the level of TAN was significantly higher in the CHP group than in the S1 and S2 groups. The EC level was also higher in the CHP group than in the S2 group. During recirculation, the ketone body ratio (acetoacetate/beta-hydroxybutyrate) was higher in the CHP group than in the S2 group. The values in the CHP group were above 1.0 after 45 min recirculation. There were no significant differences in the pyruvate/lactate ratio and lactate level between the CHP and S1 groups. However, these values were significantly different from those in the S2 group. The present findings demonstrate that CHP using UW solution and the oxygen carrier was better able to preserve the energy metabolism of the porcine liver for 72 hr than 48-hr SCS in UW solution. PMID- 1921369 TI - Perivascular sympathectomy does not remove adrenergic nerves from distal vessels. The effect of various denervations on the rat saphenous bundle: a histochemical study. AB - It has been claimed earlier that perivascular sympathectomy removes distal adrenergic innervation of the vessels. Based on preliminary results suggesting the contrary, the purpose of this work was to reconsider the denervation effect of perivascular sympathectomy. We operated on 40 rats using different denervation methods mainly to test the effects of perivascular sympathectomy on the distal saphenous vessels of the leg. The operations were performed on the right leg, while the left leg was used as a control. Samples were taken 2 days after the operations for glyoxylic acid-induced fluorescence examination for the histochemical demonstration of adrenergic nerves. Perivascular sympathectomy seemed to remove the adrenergic innervation only from the operated segment of the vessel. There was a short segment of diminished innervation a few millimeters in length just distal to the perivascular sympathectomy while the more distal adrenergic nerves around the vessels appeared to be normal. When the saphenous nerve was cut the adrenergic innervation seemed to disappear for 1 cm and to continue to be diminished at the medial malleolus site. Lumbar sympathectomy did not seem to remove the distal adrenergic nerves around the vessels, but caused only a slight decrease in innervation. It can be concluded that the peripheral adrenergic innervation is apparently normal after perivascular sympathectomy and that the operation does not have the previously assumed denervation effects. PMID- 1921368 TI - Chronic administration of growth hormone-releasing factor increases wound strength and collagen maturation in granulation tissue. AB - The effects of chronic administration of growth hormone-releasing factor (GRF) on wound healing were studied in rats. Cutaneous wound strength was measured by tensometry at 5, 10, and 14 days postwounding in rats implanted with a slow release pellet which contained a compressed mixture of a fatty acid and [desamino Tyr1, D-Ala2, Ala15]hGRF(1-29)NH2 or the fatty acid alone. There was a significant increase in wound tensile strength in GRF-treated rats compared to controls at each measurement: Day 5, 130 +/- 12 vs 97 +/- 14 g; Day 10, 402 +/- 18 vs 280 +/- 11 g; Day 14, 830 +/- 17 vs 614 +/- 14 g (P less than 0.01 for each value). Granulation tissue obtained from subcutaneously implanted polyvinyl alcohol sponges encased in silicone tubing was also studied. The amount of collagen deposited in the granulation tissue was estimated by measuring the hydroxyproline (Hyp) content of sponges retrieved 5, 10, and 14 days postinsertion from GRF-treated and control rats. Hyp content (nmole/mg sponge) was similar in both treated and control animals at each measurement: Day 5, 1.7 +/- 0.2 vs 2.2 +/- 0.2; Day 10, 31.9 +/- 4.1 vs 26.7 + 0.4; and Day 14, 41.6 +/- 7.3 vs 38.5 +/- 4.4. Hyp/proline, Hyp/glycine, and glycine/total amino acid ratios, evaluated after 10 days, were also similar in both groups. Collagen from the granulation tissue of sponges retrieved after 14 days from treated and control rats was studied by electron microscopy (magnifications, 7,100 and 22,720).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921370 TI - Vascular rejection and graft eosinophilia in rat lung allografts. AB - Allogeneic lung transplantation was performed using a rat model in order to assess the pathologic changes that developed during the process of rejection. The left lungs of 38 BN rats (RT-1n) were orthotopically transplanted into LEW rats (RT-1). The allografts developed the well-known changes of perivascular, peribronchial, and interstitial lymphocytic infiltrates resulting in necrosis of the pulmonary parenchyma at 7-8 days after transplantation. In addition, we document two findings that have not been reported previously in lung transplantation: vasculitis and eosinophilic infiltrates. Vasculitis with swelling and vacuolization of the endothelial cells was observed in transplants as early as 3 days following transplantation. Vasculitis with fibrinoid necrosis of the vessel wall was prominent at 7-8 days after grafting. The allografts also exhibited eosinophilia at 2 to 4 days following transplantation. The density of eosinophils in the inflammatory infiltrate reached a peak of 20% on Day 3 post transplantation. These findings suggest an important role of humoral immunity and a possible involvement of eosinophils in lung allograft rejection. PMID- 1921371 TI - Target cell membrane modification and susceptibility to lymphokine activated killer cell mediated lysis. I. Trinitrophenyl has no effect on murine normal cells and tumors. AB - Lymphokine activated killer (LAK) cells selectively recognize and lyse a wide variety of tumor cells, including syngeneic, allogeneic, and xenogeneic cells, by a mechanism which remains unknown. It has been shown that trinitrophenyl modification of human peripheral blood lymphocytes (PBLs) and murine blasts induces sensitivity to lysis by LAK cells. We undertook these studies to examine the effects of trinitrophenyl (TNP) on murine normal cells and tumors. Fresh murine PBLs are resistant to LAK mediated lysis and TNP modification of the cell surface has no effect, in direct contrast to results with human cells. However, the addition of anti-TNP antibody demonstrated lysis of the TNP modified cells by an antibody dependent cellular toxicity mechanism showing that these cells can be lysed by LAK cells. Furthermore, TNP did not induce sensitivity to LAK cell mediated lysis on other normal murine tissues including kidney and bone marrow. The lysis of YAC tumor cells is not inhibited by the addition of TNP modified PBLs. A single cell assay demonstrated no conjugation of LAK effector cells and TNP modified PBLs. LAK cells derived from murine PBLs, as is done in the human, were unable to lyse the TNP modified PBLs, ruling out the origin of the LAK cells as the reason for the different results in humans and mice. These observations represent a difference in the spectrum of target cells lysed by human and murine LAK cells, and also demonstrate a response to TNP modification by fresh murine normal tissues and tumors that differs from that observed with murine blasts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921372 TI - Laser-assisted fibrinogen bonding of vascular tissue. AB - Characterization of the stress-strain profiles of welded tissue would provide an additional means of analyzing this new technology and comparing it with alternative anastomosing techniques. Rabbit longitudinal aortotomies were repaired with either 7-O polypropylene sutures or an 808-nm diode laser (power density, 4.8 watts/cm2) after topical application of fibrinogen mixed with indocyanine green dye (peak absorption, 805 nm). The rabbits were sacrificed between 0 and 28 days, and the fresh aortic specimens were strained axially in diluted plasma solution until ultimate breakage occurred in order to produce a stress-strain profile graph. No significant differences were noted between sutured and bonded aorta at any time interval. Nonincised aortic tissue (378 lb/in2) withstood significantly higher stress (P less than 0.05) than both sutured (257 lb/in2) and bonded (210 lb/in2) groups at the time of creation. By 7 days after operation, however, no significant differences were noted among any of the three groups. At 28 days after operation, the laser-bonded aorta was significantly stronger than the control aorta (P less than 0.05). The only significant difference in modulus (stretchability) identified the sutured aorta (373 lb/in2) to be more rigid than the control aorta (231 lb/in2) (P less than 0.05). Both sutured and laser-bonded anastomoses are weaker than control aorta initially; however, after an early critical period, both treatments achieve the strength of control aorta. By 1 month postoperatively, sutured anastomoses have the disadvantage of being less distensible. PMID- 1921373 TI - Liver cirrhosis in rats: regeneration and assessment of the role of phenobarbital. AB - A common model for producing experimental liver cirrhosis is the administration of CCl4 to phenobarbital (PhB)-stimulated rats. However, concern may arise due to the complex actions of PhB upon liver metabolism. This study examined the role of PhB in the production of CCl4-induced liver cirrhosis in the rat. In addition, regenerative capacity of the liver after partial hepatectomy (PH) or portal branch ligation (PBL) was studied in cirrhotic rats, rats treated with CCl4 alone, and in PhB-treated controls. In rats given PhB throughout the CCl4 induction period, ascitic form of micronodular cirrhosis was found in 93% with only 3% mortality. In contrast, rats pretreated with PhB for only 2 weeks followed by CCl4 alone for 18 weeks did not develop liver cirrhosis. In most of the cirrhotic rats, PH induced hepatic regeneration associated with improved liver histology. PBL was less effective. Treatment with PhB alone for 10 weeks resulted in liver atrophy and reduced hepatic regenerative capacity. Impaired regeneration response was also found in rats treated with CCl4 alone. In conclusion, treatment with PhB throughout the CCl4-induction period seems necessary for the production of liver cirrhosis in rats. However, prolonged treatment with PhB alone results in liver atrophy and an impaired regenerative response. Therefore, though necessary for the cirrhotic model, PhB by itself has negative hepatotrophic influences which questions the thoroughness of the PhB/CCl4 experimental model. PMID- 1921374 TI - Effect of timing of cyclosporine administration on recovery from renal ischemia in rats. AB - The effect of timing of cyclosporine administration on functional recovery from renal ischemia was studied in Sprague-Dawley rats. Animals were given cyclosporine and subjected to renal ischemia by temporarily occluding both the renal artery and vein. Our data demonstrate no significant difference in serum creatinine among rats subjected to renal ischemia, cyclosporine, or cyclosporine vehicle cremophor EL administration, or the control group. On the other hand, renal ischemia in combination with cyclosporine resulted in rapid and marked deterioration in renal function with serum creatinine peaking on Day 2. The most significant rise was in rats that received cyclosporine 4 hr prior to induction of renal ischemia (4.7 +/- 0.5 mg/dl), followed by those that received cyclosporine 4 and 24 hr postischemia (2.8 +/- 0.5 and 3.2 +/- 0.7 mg/dl, respectively). Cyclosporine administration 24 hr prior to renal ischemia resulted in the least elevation of the serum creatinine (2.1 +/- 0.5 mg/dl) and the earliest return to the baseline value. Our data suggest that the timing of cyclosporine administration in rats subjected to renal ischemia influences the extent of renal injury and the subsequent recovery of renal function. PMID- 1921376 TI - Failure to use safety belts: a call to arms for Tennessee physicians. PMID- 1921375 TI - Effect of topical recombinant TGF-beta on healing of partial thickness injuries. AB - Peptide growth factors produced by platelets, macrophages, epidermal, and dermal cells may play key roles in regulating healing of partial-thickness skin wounds. We examined the effects of recombinant transforming growth factor beta (TGF-beta) on cultures of epidermal and dermal cells in vitro and on healing of partial thickness injuries in vivo. Increasing concentrations of TGF-beta (0.1, 1, and 10 ng/ml) progressively inhibited serum-stimulated DNA synthesis by up to 95% in cultures of adult human keratinocytes during 48 hr of exposure to TGF-beta. In contrast, TGF-beta (10 and 100 ng/ml) in serum-free media stimulated DNA synthesis by up to 80% compared to serum-free control cultures of adult human dermal fibroblasts. To evaluate the effects of TGF-beta on healing of partial thickness injuries in vivo, wounds (20 x 20 x 0.6 mm) were created on the dorsal thoracolumbar region of adult pigs by an electrokeratome and were treated daily for 5 days after injury with vehicle or vehicle containing 0.1 or 1 microgram/ml TGF-beta and covered with occlusive dressing. Computerized planimetry of wound photographs demonstrated that TGF-beta treatment stimulated statistically significantly increases in the area of regenerated epidermis compared to wounds treated with saline vehicle on Days 3, 4, 5, and 7 after injury probably due to TGF-beta increasing the rate of epidermal cell migration. In addition, morphometry of biopsy specimens showed that TGF-beta treatment stimulated statistically significant increases in the cross-sectional depths of regenerated dermis compared to wounds treated with saline or Silvadene vehicles on Days 5, 6, and 8 after injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921377 TI - Traumatic hemipelvectomy. PMID- 1921378 TI - Stiff neck and fever in a nursing home patient. PMID- 1921379 TI - Radiology case of the month. Meniscal cyst. PMID- 1921380 TI - Results of 1990 immunization survey of 24-month-old children. PMID- 1921381 TI - Loss prevention case of the month. Take your time--be sure. PMID- 1921382 TI - Gifts to physicians from industry. AMA Council on Ethical and Judicial Affairs. PMID- 1921383 TI - Cancer incidence in Tennessee: data reported to the Tennessee cancer reporting system 1986-1988. Tennessee Cancer Reporting Advisory Committee. PMID- 1921384 TI - Multi-agent chemotherapy in a case of non-Hodgkin's lymphoma in second trimester of pregnancy. PMID- 1921386 TI - Hereditary angioneurotic edema. PMID- 1921385 TI - Open pelvic fracture: a multidisciplinary injury. PMID- 1921388 TI - Herpes gestationis following normal first pregnancy. PMID- 1921387 TI - A case of recurrent pneumonia. PMID- 1921389 TI - Who said it would be fair? PMID- 1921390 TI - Childhood lead poisoning prevention. PMID- 1921391 TI - Patient relations guidelines: dealing with your patients on the telephone. TMA Communications and Public Service Committee. PMID- 1921392 TI - Venereal diseases: a historical perspective. PMID- 1921393 TI - Documenting the right to die. PMID- 1921394 TI - Extended single transverse neck incision for composite resections: does it work? AB - Since Crile's original description of neck dissection in 1906 (Crile GW: JAMA 47:1780-1786, 1906), a variety of neck incisions has been described, suggesting that none is sufficiently versatile to satisfy the criteria necessary for the ideal neck flap. Single transverse neck incisions (STNI) for complete neck dissections have been performed since the 1950s but are not as commonly used as trifurcate incisions. A criticism of the STNI is that the perceived difficulty exposing the surgical field may compromise removal of disease and impair normal surgical technique, resulting in a higher incidence of recurrent neck disease and postoperative complications. One hundred nine patients with squamous cell carcinoma of the head and neck were operated using the STNI. There was no incidence of skin necrosis or carotid artery hemorrhage. Fourteen percent developed fistulae and 12% developed wound dehiscences. Recurrence in the operated neck was not identified. Cosmesis was considered good in all patients. We conclude that STNI does not result in an increased incidence of postoperative complications or recurrent neck disease compared with standard trifurcate incisions. PMID- 1921395 TI - Lymph node metastasis in thoracic esophageal carcinoma. AB - Seventy-nine patients with thoracic esophageal carcinoma underwent transthoracic esophagectomy with neck, mediastinal, and abdominal lymphadenectomy. The operative mortality rate was 3.8%. Fifty-seven patients (72.2%) had metastasis in the lymph nodes. Though three patients with carcinoma classified as pTis had no positive nodes, nine (50.0%) of the patients with a pT1 carcinoma had positive nodes. The 5-year survival rate for 57 patients with positive nodes was 33.6%. Twenty-nine patients (36.7%) had positive nodes in the neck; 47 (59.5% ), in the mediastinum; and 33 (41.8%), in the abdomen. Their 5-year survival rates were 30.0%, 24.4%, and 38.4%, respectively. The differences between these rates were not statistically significant. These results indicate that the neck lymph nodes should be regarded as part of the regional lymph nodes and that esophagectomy with wide lymph node dissection improves the long-term survival of patients with thoracic esophageal carcinoma. PMID- 1921396 TI - Metastases to the breast: differential diagnosis from primary breast carcinoma. AB - Eight patients with breast metastases from primary tumors other than breast carcinoma were studied: 3 malignant melanomas, 2 rhabdomyosarcomas, 1 malignant mesothelioma, 1 appendiceal carcinoid, and 1 epidermoid cervical carcinoma. All had mammographic, histopathologic, and immunohistochemical examinations. The main problem was differential diagnosis from primary breast carcinoma. History of extramammary primary tumor was helpful but breast metastasis was the first clinical feature in 2 cases. Patients had noticed palpable, round, rapid growth masses which were mammographically benign. Pathologic diagnosis was difficult and immunohistochemical studies necessary, whenever the proliferation had histologic features of primary breast carcinoma or when no primary tumor was known. However, some histologic features were of value for diagnosis of metastasis: atypical histologic features for a primary breast carcinoma, a well-circumscribed tumor with multiple satellite foci, the absence of an intraductal component, and the presence of many lymphatic emboli. In adults, the most frequent types of tumors metastasizing in the breast are malignant melanoma and neuroendocrine-like tumors, especially small cell carcinoma and carcinoid. In children, rhabdomyosarcoma is the most common. Accurate diagnosis of breast metastasis is important to avoid unnecessary mastectomy and to implement an appropriate systemic therapy. PMID- 1921397 TI - Cytoreductive surgery impedes metastasis and enhances the immune response: a preliminary report. AB - In an effort to determine the effect of cytoreductive surgery on the metastatic process, MAT-LyLu flank tumors were excised from Copenhagen x Fischer rats and the effects of this surgery on metastatic lung lesions were observed. Cytoreduction resulted in a decrease in lung lesions (P less than 0.05). Adjuvant cyclophosphamide (CTX) further enhanced this beneficial effect. A concurrent increase in the helper/suppressor ratios suggested that this beneficial response might be mediated by the host's immune response. PMID- 1921398 TI - A phase II pilot study of the combined application of hyperthermia and intra hepato-arterial chemotherapy using cisplatinum and 5-fluorouracil. AB - Fourteen patients (group A) with unresectable metastasis to the liver from colorectal cancers (11 patients) and gastric cancers (3 patients) were treated with the combined application of hyperthermia and intra-hepato-arterial (IHA) chemotherapy with cisplatinum and 5-fluorouracil. Ten patients were treated with regional hyperthermia applied with a radiofrequency capacitive heating system and four patients were treated with total-body hyperthermia concurrently with IHA chemotherapy. Thirty-one patients (group B) with liver metastases from colorectal and gastric cancers received only IHA chemotherapy with the same chemotherapeutic regimen. In group B, partial responses (PRs) were obtained in 8 of 17 evaluable patients with colorectal cancer and in 1 of 10 evaluable patients with gastric cancer. In group A, PRs were found in 6 of 11 patients with colorectal cancer and in 2 of 3 patients with gastric cancer. Furthermore, improvements due to the combination of chemotherapy with hyperthermia were noted in 3 of 6 patients with colorectal cancer who had received unsuccessful prior IHA chemotherapy. The 50% survival period was prolonged to 23 months in group A from 11 months in group B, for patients with colorectal cancer. Toxicity of IHA chemotherapy was not potentiated by combination with hyperthermia. These results indicate that the combination of hyperthermia with IHA chemotherapy has a therapeutic benefit in the treatment of unresectable metastatic liver tumors derived from colorectal and gastric cancers. PMID- 1921399 TI - Thoracoscopy in the diagnosis of pleural effusion of ambiguous etiology. AB - Between 1985 and 1989, 27 patients underwent thoracoscopy for an undiagnosed pleural effusion. Prior thoracocentesis (in all patients) and a needle pleural biopsy (in 15 patients) had been nondiagnostic. The rigid thoracoscope was used in 21 patients, the cystoscope in 4 patients, and the flexible bronchoscope in 2 patients. We had one mortality, and there was no operative morbidity. Thoracoscopy was diagnostic in 24 of the 27 patients (4 benign, 20 malignant). The average duration of stay in the hospital was 48 hr. We conclude that thoracoscopy is an important diagnostic aid in the management of a pleural effusion of ambiguous origin and that it is a relatively safe procedure that can be performed with an acceptable morbidity and mortality. PMID- 1921400 TI - Comparison of R1 and R2 gastrectomy for gastric cancer in patients over 80 years of age. AB - To evaluate the benefit of R2 gastrectomy for gastric cancer in Japanese patients over 80 years of age, data on 93 patients who underwent gastrectomy between 1967 and 1989 were collected retrospectively from charts filed in the Kyushu University Hospital and two affiliated national hospitals. Of 93 patients, 62 had a localized tumor without evidence of metastatic spread. These 62 patients were classified into two groups according to the procedures performed: 35 underwent R1 gastrectomy and 27, R2 gastrectomy. The clinical and pathological characteristics of the patients in the two groups were comparable at the time of surgery, except that the group who underwent R1 gastrectomy was older. R2 gastrectomy involved a significantly longer operation time (P less than 0.01) and greater intraoperative blood loss (P less than 0.05) when compared to R1 gastrectomy, but no patient undergoing this extensive surgery died. The difference in the morbidity rate between the two groups was not statistically significant. The 5-year survival rate was 55.8% in the R1 group and 65.4% in the R2 group. When gastric cancer invaded the serosa and/or secondary nodes, a substantial increase in survival time was gained with R2 gastrectomy when compared to an R1 operation. These findings suggest that an R2 gastrectomy is feasible, even for patients over 80 years, but is indicated mainly when the carcinoma had invaded the serosa and/or secondary nodes and the patients are at good risk for major surgery. PMID- 1921401 TI - Pulmonary clear cell carcinoma. AB - A case of pulmonary clear cell carcinoma is demonstrated. A large left lower lobe mass, without lymphadenopathy was detected on a screening chest X-ray, and a left lower lobectomy was performed. The tumor was composed predominantly of clear cells with some areas showing cells typical for small cell carcinoma. Ultrastructurally, the larger clear cell had cytoplasm containing many rough endoplasmic reticuli and free ribosomes, while the smaller dark cell showed a serrated nucleus and scanty cytoplasm having many free ribosomes without neurosecretory granules. This is the first report on pulmonary clear cell carcinoma with small cell carcinoma patterns, and this case will throw doubt on the conclusion of previous studies that clear cell carcinoma is not a separate entity. PMID- 1921402 TI - Early hilar lung cancer: its clinical aspect. AB - Early hilar lung cancers are rare, but are curable if they are properly diagnosed and treated. In the past 14 years, we have treated 27 patients with early hilar cancers that fulfilled the criteria proposed by the Japanese Lung Cancer Society (JLCS). Eighteen patients presented with symptoms and 9 were detected by the mass screening examination of sputum cytology. All lesions in both groups were finally diagnosed by bronchoscopy. Twenty patients (74%) had positive sputum cytology, whereas only 7 (26%) had positive chest X-ray findings. All the patients underwent surgery, and bronchoplasty was the most frequent operative procedure. The 5-year survival rate was 100%, and the 10-year survival rate was 91.7%, as one patient died of a second primary lung cancer in the 6th postoperative year. In conclusion, the definition of early hilar lung cancer proposed by the JLCS is thought to be reasonable, and early hilar lung cancer is a curable disease, if it is properly diagnosed and treated. PMID- 1921403 TI - The effect of head and neck cancer treatment on whole salivary flow. AB - The effects of multimodality therapy for head and neck cancer on whole salivary flow were evaluated. Eighteen subjects with head and neck cancer were studied. Resting and stimulated whole salivary flow rates were recorded, pretreatment, after individual modality therapy, and posttreatment. Twenty-four subjects with no history of head and neck cancer matched for age, and sex distribution, served as controls. Primary site, stage, major salivary glands resected, radiation fields, and dose to major salivary glands are reported. The average salivary flow rates for 18 subjects following treatment was reduced 83% for resting and 86% for stimulated saliva from pretreatment levels. The null hypothesis that the overall resting and stimulated whole salivary flow rates are unaffected by treatment (surgery and radiation) of the head and neck cancer was rejected (P values at 0.05 level of significance). Stage and location of primary, total dose delivered to and volume of gland exposure are important factors when predicting xerostomia following multimodality therapy. PMID- 1921404 TI - Prognostic factors in laryngeal cancer patients submitted to surgical treatment. AB - The authors studied some demographic, clinical, pathologic, and therapeutic variables in relation to the disease-free interval (DFI) and to the overall survival of laryngeal cancer patients. The patient population consisted of 278 consecutive cases of primary laryngeal cancer who had been admitted to four head and neck surgery services in Sao Paulo and Curitiba (Brazil) between 1973 and 1986. All patients had surgical treatment. Although several variables exhibited individual associations with survival, only a few were deemed to have independent prognostic value using multivariate regression techniques based on Cox's proportional hazards model. The primary tumor stage (T index) represented the variable with the highest predictive strength with respect to survival. Hazard ratios for the risk of disease recurrence were 2.3 (T2-3 vs. T1) and 4.3 (T4 vs. T1). Hazard ratios for the risk of death were 1.6 (T2-3 vs. T1) and 3.3 (T4 vs. T1). The following additional factors were also independently associated with the DFI: age, site of primary tumor (transglottic, glottic, or supraglottic), extracapsular spread of lymph node metastasis, surgical margins, type of paratracheal node dissection, and prior tracheostomy. Except for extracapsular spread, the same factors related to the DFI were also significantly related to the overall survival. Race, sex, N-stage, vascular embolization, and histological grade were other independent predictors of the risk of death. PMID- 1921405 TI - Establishment of a human chorionic gonadotropin-producing human gastric carcinoma in nude mice. AB - A human chorionic gonadotropin (HCG)-producing gastric carcinoma was transplanted into BALB/c nu/nu nude mice. The original tumor tissue had been obtained by gastrectomy from a 55-year-old patient with gastric carcinoma. The tumor was transplanted serially in nude mice, and its doubling time was stable to approximately 12 days. A positive correlation was observed between serum HCG level and tumor weight. The serum HCG level of the mice and the histology of the tumor weight. The serum HCG level of the mice and the histology of the tumor, papillary adenocarcinoma with partial poorly differentiated adenocarcinoma, did not change on serial transfers. HCG was positively stained by an immunochemical technique only in the site of the poorly differentiated adenocarcinoma, while staining was negative in the site of the papillary adenocarcinoma, which constituted most of the tumor. These results indicate that this tumor in nude mice will be useful not only as a therapeutic experimental system but also for studying the potential malignancy of HCG-producing cancer cells. PMID- 1921406 TI - Methods and limitations of an experimental model of long QT syndrome. AB - An experimental model of the long QT syndrome has been developed in conscious dogs. This report discusses the methods used in its preparation and the strengths and weaknesses of the model. This new model is suitable for screening the bradycardia-dependent proarrhythmic effects of drugs and for studying the electrophysiology of "torsades de pointes." Permanent bradycardia (RR: 1558 +/- 83 ms) was obtained in 37 dogs by chemically-induced complete atrioventricular block. A 10% further increase of ventricular repolarization (QT: 306 +/- 7.0 ms to 331 +/- 5.5 ms) was obtained in 28 of these dogs by diuretic-induced hypokalemia. Diuretics, despite saline replacement, induced some degree of functional renal failure and extracellular volume losses. The QT interval increased although ventricular cycle length decreased slightly. These biological and electrophysiological parameters were reproducible except for a slow increase in plasma creatinine. Cardiac failure and sudden death rarely occurred. The most severe, but reversible, renal failure occurred in some dogs given the highest diuretic doses. Hypokalemia resulted in ventricular arrhythmias in only 6 dogs, 2 of them exhibiting runs of ventricular tachycardia and even "torsade de pointes" as their potassium levels fell below 2 mmol/L. The results of studies with several drugs using the model, with or without hypokalemia, or with bradycardia worsened by propranolol are analysed. PMID- 1921407 TI - Assessment with potential mapping of the cardiac protective effect of a drug. Example of trimetazidine. AB - SATAPEC is a computerized system built in the Laboratory for recording over 256 multiplexed channels and for automatic processing of cardiac electrical potentials. The results are printed out in the form of maps (either in black and white or in color) showing potential distributions, depolarization, repolarization, duration of activation, or various other analog-digital data. The cardioprotective ability of a drug may be assessed with SATAPEC. As an example, the effect of trimetazidine (TMZ) is examined using 2 groups of 12 rabbits (one group serving as a control and the second group pretreated with TMZ). An elastomer mesh with 240 regularly spaced chlorided silver wire electrode is placed around the ventricles following thoracotomy. A ligature is made starting from the anterior interventricular artery (AIV). Recordings are taken from the 240 unipolar epicardial electrograms (reference potential taken at Wilson terminal) 1 min before ligation and then every min for 8 min following ligation. Once the electrograms are plotted and any aberrant tracings eliminated, ST variation is calculated automatically. Files containing ST variations at different instants are stored in the computer memory and the mean sigma ST/240 curves of the two groups of rabbits are plotted versus time. Mean electric potential maps, obtained by aligning all of the individual maps, are then printed. With these maps the location and extent of the epicardial injured area can be visualized. Pretreatment with TMZ (2.5 mg/kg) has shown a beneficial effect on ischemia injury. PMID- 1921408 TI - A quantitative method for measuring labeled compounds with whole-body autoradiography in tissue sections. AB - Whole-body autoradiography is an effective method for localizing labeled compounds in various organs. However, the technique is limited in its ability to quantify such material. Using tissue sections, this study investigated certain parameters involved in the quantitative estimation of labeled compounds by whole body autoradiography. These included correlation between thickness of the section and radioactivity counted, the precision of such measurements, and the reproducibility of the autoradiographic films as tested by image analysis transmission. The precision of radioactivity measurements using tapes with a tissue section or a "punch biopsy" (punching off a piece of tissue from the section) was compared. The results revealed excellent linearity between the thickness of the section and the radioactivity counted (r = 0.97) when section thickness was 10-30 microns. The measurement precision using tapes was better than with the "punch specimen" method. The reproducibility of photographic films was good when transmission was measured by image analysis. It was concluded that a thickness of 30 micron is ideal for use in whole-body autoradiographic studies. It appeared that radioactivity measurement of tissue sections on tapes was superior to direct measurement from organs. Image analysis was employed and statistically evaluated for the first time in this study, and the promising findings suggest that it is likely to become the method of choice for future studies of this type. PMID- 1921409 TI - Comparison of a fluorimetric and a colorimetric method for the determination of hydrogen peroxide production by rat pleural macrophages. AB - A fluorimetric and a colorimetric method for the determination of hydrogen peroxide (H2O2) production by isolated cells were compared. Despite a higher sensitivity of the fluorimetric assay, using homovanillic acid (HVA) as reagent, a significantly lower H2O2 production by rat pleural macrophages was measured in comparison to the colorimetric phenol red method. A negative influence of HVA on H2O2 production was detected in the colorimetric assay. These results suggest that the fluorimetric assay with HVA is unsuitable for determining H2O2 formation by isolated cells. PMID- 1921410 TI - Rapid and selective measurement of platelet-activating factor using a quantitative bioassay of platelet aggregation. AB - A bioassay for the measurement of platelet-activating factor (PAF) based on the quantification of platelet aggregation was developed. The method used a platelet analyzer in conjunction with a multiwelled micromixing device and whole blood collected from male New Zealand White rabbits. This bioassay can be nonselective and used to quantitate platelet aggregation induced by any activator. The EC50 for platelet-activating factor, arachidonic acid, and adenosine diphosphate were 0.0232, 55, and 10 microM, and at these concentrations the half maximal aggregation response occurred at 7.5, 10.0, and 12.5 min, respectively. The bioassay was capable of the sensitive quantification of platelet aggregation in small volumes (50 microL) of citrated rabbit whole blood, using a short (i.e., 15 min) incubation period. This enabled multiple bioassays to be performed without the need for a large volume of whole blood to be collected from the rabbit. Selective measurement of platelet-activating factor was achieved by adding inhibitors of arachidonic acid- and adenosine diphosphate-dependent pathways of platelet activation, that is, acetylsalicyclic acid and phosphoenolpyruvate/pyruvate kinase, respectively, to the citrated rabbit whole blood immediately before bioassay. These inhibited arachidonic acid- and adenosine diphosphate-induced platelet aggregation, but had no effect on platelet aggregation induced by platelet-activating factor. Platelet-activating factor was selectively inhibited by its receptor antagonist BN 52021. This method for measuring platelet-activating factor was reproducible; at the EC50, the inter- and intrabioassay coefficients of variation were within acceptable limits at 13.17% and 9.75%, respectively. PMID- 1921411 TI - A new method for measuring auricular inflammation in the mouse. AB - The croton oil ear test is widely used to identify prospective topical antiinflammatory drugs. Ear inflammation is produced by applying a 2% solution of croton oil on the ears of mice or rats. The effectiveness of the drug that is dissolved in the croton oil solution can be gauged by comparing the croton oil treated ears with the croton oil plus drug treated ears. The effect is measured following sacrifice of the animal by weighing either the excised ear (Tonelli et al., 1965; Glenn et al., 1978; Swingle et al., 1981; Soliman et al., 1983; Mantione and Rodriguez 1990) or a plug taken from the ear (Tubaro et al., 1985; Davis et al., 1989a; Davis et al., 1989b). Use of this technique for the generation of a time-course evaluation of antiinflammatory activity requires a large amount of the chemical to be tested and the sacrifice of many animals. In other assays, ear thickness has been measured by caliper (Carlson et al., 1985; Maloff et al., 1989) or by dial micrometer (Griswold et al., 1987), which allow multiple measurements to be made, but the pressure on the ear was not reported. In a recent review of pharmacological methods, Chang and Lewis (1989) caution that using calipers to measure ear thickness is subject to operator error and bias. Furthermore, they emphasize care must be taken to not leave the calipers in contact with the ear too long, as it is possible to squeeze substantial amounts of edema fluid out of the ear tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921413 TI - Abstracts, 20th annual meetings. Keystone Symposia on Molecular and Cellular Biology. Intermediate biomarkers of precancer and their applications in chemoprevention. October 3-7, 1991. PMID- 1921412 TI - Assessment of antinociceptive drug effects in the presence of impaired motor performance. AB - The hot-plate (HP) and tail-flick (TF) tests are widely used to assess analgesic activity of drugs. These tests do not directly measure the intensity of the noxious stimulus perceived by the animal, but only the animal's response to it, and so may be affected by non-analgesic drugs. Sedatives and muscle relaxants, for example, may impair the ability to respond and hence be wrongly considered to have analgesic activity. We examined response of rats in the HP (55 degrees C, cutoff time 25 sec) and TF (cutoff time 5 sec) tests following administration of pentobarbitone, diazepam or pancuronium. These drugs all impaired motor performance as assessed by reduction in mean rotarod performance times to 6-32% of predrug values. However, HP and TF latencies were not appreciably prolonged. We also found that pancuronium did not alter effects of morphine on HP or TF latencies, despite reduction in rotarod performance to 38% of predrug values. Our results support the validity of HP and TF tests as analgesic assays even in the presence of substantial impairment of motor performance. PMID- 1921414 TI - In support of ANA's opposition to mandatory HIV testing. PMID- 1921415 TI - Effects of embelin, a male antifertility agent, on absorptive and digestive functions of rat intestine. AB - Oral administration of embelin (75 mg/kg per day, daily for 15 and 30 days) to male rats caused significant elevation in the uptake of D-glucose, L-alanine, L leucine and calcium in small intestinal segments. Embelin also produced significant increases in intestinal brush border membrane-associated enzymes (sucrase, lactase, maltase, alkaline phosphatase and leucine aminopeptidase) in both intestinal homogenates and partially purified brush border membrane preparations. Significant increases were also noted for microsomal glucose-6 phosphatase and cytosolic lactate dehydrogenase. Increase in brush border membrane-associated total lipids, phospholipids, cholesterol, triacylglycerol, unesterified fatty acids and ganglioside sialic acid were seen but not in the cholesterol/phospholipid molar ratio. All these changes returned to control or near control levels following withdrawal of the drug. PMID- 1921416 TI - Pharmacological properties of Moringa oleifera. 1: Preliminary screening for antimicrobial activity. AB - The antimicrobial activities of Moringa oleifera leaves, roots, bark and seeds were investigated in vitro against bacteria, yeast, dermatophytes and helminths pathogenic to man. By a disk-diffusion method, it was demonstrated that the fresh leaf juice and aqueous extracts from the seeds inhibit the growth of Pseudomonas aeruginosa and Staphylococcus aureus and that extraction temperatures above 56 degrees C inhibited this activity. No activity was demonstrated against four other pathogenic Gram-positive and Gram-negative bacteria and Candida albicans. By a dilution method, no activity was demonstrated against six pathogenic dermatophytes. A method was standardized for studying the effect of aqueous extracts on Ascaris lumbricoides eggs, but no activity was exhibited by any part of the tree in contrast to Chenopodium ambrosioides leaf extracts. PMID- 1921417 TI - Study of Costus lucanusianus: plant juice, fraction combinations and pharmacologic estimation of natural product total activity. AB - The juice of Costus lucanusianus fresh stems was split by chromatography using pharmacological measurements on duodenum and uterus to follow activity. The concentration-effect curves of the parent juice and the active fraction alone or associated with other fractions were analysed according to classical methods used for combination drugs. Results show that the active fraction is potentialised by two groups of fractions which are without intrinsic activity. PMID- 1921418 TI - Traditional methods used in the treatment of ophthalmic diseases among the Turkana tribe in north west Kenya. AB - A survey of traditional methods used in the treatment of ophthalmic diseases was conducted among the Turkana tribe in north-west Kenya. The data was collected from people who suffered from chronic eye diseases. Most of the remedies were prepared from plants and fruits because of their availability in the Turkana region. Some of the other remedies were prepared from animal sources. Most people reported worsening of their eye problems, probably due to improper or unhygienic applications. The collected data can be an example of use of traditional eye treatment in remote African arid and semi-arid areas. PMID- 1921419 TI - Antimalarial activity and cytotoxicity of Evodia fatraina stem bark extracts. AB - Stem bark extracts of Evodia fatraina (Rutaceae) were tested for antimalarial activity in vitro on Plasmodium falciparum using an isotopic semi-microtest and in vivo on Plasmodium berghei in mice. Ethyl acetate extract showed moderate antimalarial activity in vitro (IC50 = 8.5 micrograms ml-1). However, ethanolic extract exhibited significant potency in vivo (65% suppression of parasitaemia). Moreover, low toxicity against HeLa cells and L 929 fibroblasts was observed with ethanolic extract (IC50 = 95 micrograms ml-1 and 60 micrograms ml-1, respectively). PMID- 1921420 TI - Merging pharmacopoeia: understanding the historical origins of incorporative pharmacopoeial processes among Xhosa healers in southern Africa. AB - This paper focusses on Xhosa healers and their pharmacopoeias in Southern Africa. Its preliminary aim is to show that Xhosa healers have incorporated Western pharmaceutical products into their traditional dispensaries. The primary aim of the paper is to explain the trend towards medicinal incorporation in terms of the historical development of health and health care in Xhosa-speaking regions. Finally, it is suggested that Xhosa healers utilise Western medicines for their symbolic value, allowing them to negotiate some of the historical precedents which have had the effect of marginalising their profession. PMID- 1921421 TI - The effectiveness of Hernandia spp. (Hernandiaceae) in traditional Samoan medicine and according to scientific analyses. AB - The use of Hernandia nymphaefolia (Presl.) Kubitzki, Hernandia ovigera Linn., Hernandia peltata Meissner and Hernandia sonora Linn. in traditional Samoan medicine is given. The constituents have been listed and the effectiveness of the various plant parts deducted from them. A comparison of the traditional medicinal use with the assigned medicinal effectiveness shows clear concordances. Further pharmacological investigations are needed. PMID- 1921422 TI - Xanthine oxidase inhibitory activity of Chilean Myrtaceae. AB - Twenty-one Myrtaceae collections belonging to 10 species, 5 of which are used in Chilean folk medicine, were assayed for inhibitory activity towards the enzyme xanthine oxidase. Most leaf and stem extracts were devoid of activity or showed a weak inhibitory effect. Chilean ethnobotanical data on the species are linked to the astringent properties of Myrtaceae and their use for treating wounds and diarrhea. The results show the advantage of using proper plant selection criteria when searching for new drugs to treat human gout. PMID- 1921423 TI - Effect of calcium and verapamil on renal function of rats during treatment with stevioside. AB - A study conducted on rats using classical clearance techniques and arterial pressure measurements showed that stevioside from Stevia rebaudiana leaves produced a fall in systemic blood pressure, as well as diuresis and natriuresis per milliliter of glomerular filtration rate. Verapamil tended to increase the renal and systemic effects of stevioside. In contrast, an infusion of CaCl2 in rats prepared with stevioside induced a marked attenuation of the vasodilating responses of stevioside. These data are consistent with the possibility that stevioside may act as a calcium antagonist, as is the case for verapamil. PMID- 1921424 TI - Antiinflammatory activity of a Ghanaian antiarthritic herbal preparation: I. AB - A boiling water extract from a powdered sample containing Alstonia boonei root bark (90%) Rauvolfia vomitoria root bark (5%) and Elaeis guineensis nut without pericarp (5%) was tested intraperitoneally for its antiinflammatory activity by measuring rat hindpaw edema induced by the subplantar injection of carrageenin in the presence or absence of arachidonic acid. Arachidonic acid increased swelling during the early phase of carrageenin edema. The extract suppressed the late phase of carrageenin edema and both phases in the presence of arachidonic acid. These preliminary results are consistent with a herbal preparation known to be used in the management of rheumatoid arthritis. PMID- 1921425 TI - Brahmighritham, an Ayurvedic herbal formula for the control of epilepsy. AB - Brahmighritham is an Ayurvedic herbal recommended for the control of epilepsy. The preparation of the drug is described. It was tested for its oral effectiveness in controlling pentylenetetrazole-induced seizures in male albino rats and was compared with benzdiazepam. Alterations in the EEG pattern and gross neurological function were measured or rated 60 min after pentylenetetrazole administration. Thirty-day pretreatment with both Brahmighritham and benzdiazepam served to make the rats more insensitive to epileptogenic events. PMID- 1921426 TI - Plants used in Guatemala for the treatment of dermatomucosal infections. 1: Screening of 38 plant extracts for anticandidal activity. PMID- 1921427 TI - Croton zehntneri: possible central nervous system effects in rodents. PMID- 1921428 TI - Traditional medicinal plants of Thailand. XVII. Biologically active constituents of Plumeria rubra. AB - The compounds 1-6 were isolated from the heartwood of Plumeria rubra, following bioactivity-directed fractionation. Plumericin 1 and isoplumericin 2 displayed molluscicidal, cytotoxic and antibacterial activity, 4-hydroxyacetophenone 3 was weakly cytotoxic, whereas the remaining glycosidic isolates (plumieride, 4; 13-O coumaroylplumieride, 5; protoplumericine A, 6) were inactive in all test systems. PMID- 1921429 TI - In memoriam O. Theron Clagett (1908-1990). PMID- 1921430 TI - Blood and brain tissue gaseous strategy for profoundly hypothermic total circulatory arrest. AB - Brain tissue carbon dioxide tension, pH, and oxygen tension were measured in dogs undergoing hypothermic circulatory arrest below 20 degrees C with three types of blood gas manipulation. During core cooling, dogs were given pure oxygen (group I, n = 8), 5% carbon dioxide in oxygen (group II, n = 10), or 7% carbon dioxide in oxygen (group III, n = 4). During core cooling, brain tissue carbon dioxide tension decreased significantly in group I. During circulatory arrest, carbon dioxide tension rose by 21.5 mm Hg in group I, 35.3 mm Hg in group II, and 57.0 mm Hg in group III, nearly doubling in each group. From the last 5 minutes of core cooling to the end of rewarming, carbon dioxide tension was significantly higher in groups II and III than in group I. Brain tissue pH fell by 0.33 to 0.35 during 60 minutes of circulatory arrest and did not recover in groups II and III. Brain tissue oxygen tension decreased significantly during the latter two thirds of the circulatory arrest period in all three groups. To reduce progressive tissue hypercapnia and acidosis during and after circulatory arrest, a more hyperventilatory manipulation of blood gases than that achieved by alpha-stat strategy was thought beneficial for core-cooling perfusion. PMID- 1921431 TI - Angiographic assessment of graft patency after coronary endarterectomy. AB - Fifty-one consecutive patients underwent 68 manual core endarterectomies between April 1985 and May 1987. There were 42 men and nine women, mean age 60 years (range 39 to 81). All patients underwent coronary bypass grafting alone. There were no reoperations. There was one operative death (2%). Forty patients consented to early (mean 19 days) and 27 to late (mean 19 months) repeat angiography. At the early restudy 47 of 52 (90%) grafts to endarterectomized vessels were patent. This rate fell to 27 of 42 (64%) at late restudy. There was considerable variation in the angiographic appearance of the endarterectomized vessels, ranging from a large caliber, smooth walled vessel to an attenuated vessel with irregular walls. In general, there was a tendency toward "shrinkage" of these vessels by the late restudy, suggesting fibrosis in the walls. We conclude that, although endarterectomy can be done on most atheromatous vessels with excellent early graft patency, these vessels tend to show an accelerated deterioration with time, resulting in a low late patency rate. We suggest that the procedure be reserved for vessels that are truly inoperable by other means and only for vessels that supply a coronary bed of at least moderate size. PMID- 1921432 TI - Origin of the left coronary artery from the pulmonary artery in older adults. AB - Origin of the left coronary artery from the pulmonary artery is usually a serious clinical problem; untreated, it often causes death. Usually the condition becomes symptomatic early in life, but occasionally symptoms do not manifest until later in childhood. A smaller group will not have symptoms until early adulthood. Rarely, this lesion may be asymptomatic for decades. The reports in the literature and our experience with surgical correction of this condition in patients in their sixth and seventh decades of life are described. One patient is the oldest reported in the world literature to have this condition. PMID- 1921433 TI - Valvuloplasty for aortic insufficiency. AB - Twenty-eight consecutive patients underwent aortic valvuloplasty for aortic insufficiency caused by leaflet prolapse. The technique involved triangular resection of the free edge of the prolapsing leaflet, annular plication at the commissure, and resection of a raphe when present in bicuspid valves. Mean age of the patients was 46.8 +/- 14.4 years. Twenty-six (92.7%) were male. Seventy-five percent of the patients had a bicuspid aortic valve; the remaining valves were tricuspid. The extent of aortic insufficiency was 3.6 +/- 0.8 by aortography, 3.1 +/- 0.1 by preoperative Doppler echocardiography, and 3.4 +/- 0.7 by intraoperative Doppler echocardiography. The amount of aortic insufficiency decreased from 3.4 +/- 0.7 to 0.6 +/- 0.5 intraoperatively, immediately after repair (p less than 0.001). Mean transvalvular gradient by echocardiography was 12.9 +/- 6.8 mmHg. There was one death in a patient who had an intraoperative cerebral vascular accident. Mean follow-up was complete at 6.9 months. One patient had a cerebral vascular accident and one patient required reoperation for recurrent aortic insufficiency caused by partial suture line dehiscence. In 15 patients with late echocardiograms, aortic insufficiency did not progress (0.7 +/ 0.6 in the hospital and 0.8 +/- 0.5 late). Aortic valve repair for aortic cusp prolapse effectively eliminates aortic insufficiency without causing aortic stenosis. At early follow-up the repair has been stable. PMID- 1921434 TI - Clinical experience with the Novacor ventricular assist system. Bridge to transplantation and the transition to permanent application. AB - At Stanford University, a Novacor left ventricular assist system (Baxter Healthcare Corporation, Novacor Division, Oakland, Calif.) was placed as a bridge to heart transplantation in 13 patients. During the hospitalization preceding device implantation, all patients were receiving inotropic support for biventricular failure, 11 had pulmonary edema, 6 had life-threatening ventricular arrhythmias, 5 had liver dysfunction with coagulopathy, and 2 had renal failure necessitating artificial support. The mean cardiac index before implantation of the Novacor system was 1.5. All survivors with the Novacor device had a dramatic increase in cardiac output (mean cardiac index = 3.1). One patient with cardiac allograft rejection died during implantation of the left ventricular assist system. Two patients died of pulmonary sepsis and multiorgan failure after the device was implanted. All patients who had the Novacor device implanted for more than 7 days were able to walk and ride stationary bicycles while awaiting transplantation. Ten patients (77%) underwent successful heart transplantation after a mean of 18 days' support with the Novacor device. One patient died of presumed sepsis 2 days after transplantation. Nine patients (90%) are alive 4 months to 6 years after transplantation. In the overall United States experience, 68 patients (as of May 1990) have had a Novacor left ventricular assist device implanted. Five were still being supported, 39 had received a transplant (62%), and 35 patients (90%) survived the transplant hospitalization (1 died later). No instances of device failure have occurred. Overall, the Novacor assist system provided effective bridging to transplantation, with posttransplant survival similar to results after routine transplantation. Modifications and improvements based on this clinical experience have been made in the areas of patient selection, techniques of operative placement, postoperative management, and design of the assist system. Isolated left heart support with a fully implantable left ventricular assist system will be offered as an alternative to heart transplantation for selected patients by 1992. PMID- 1921435 TI - Effects of acute right ventricular ischemia on ventricular interactions during prosthetic left ventricular support. AB - Systolic ventricular interactions may be partially responsible for right ventricular failure that sometimes occurs during clinical use of prosthetic left ventricular assist devices. In this hypothesis, it is proposed that the left ventricular assist device reduces left ventricular pressure and its contribution to right ventricular performance, thus impairing right ventricular output. On the other hand, these effects may be small compared with other causes of right ventricular failure such as ischemia. To test the systolic interaction hypothesis in the normal and ischemic right ventricle, we used a left ventricular assist device to pressure unload the left ventricle of anesthetized pigs, and we compared its effect on right heart function before and after 2 minutes of acute right coronary artery occlusion as a model of right heart failure. Pigs were instrumented for measurements of septal to left ventricular and right ventricular free wall dimensions with ultrasonic crystals, ventricular chamber pressures, and cardiac output with a pulmonary artery blood flow probe. Without right ventricular ischemia, the left ventricular assist device produced an 80% +/- 6% reduction in left ventricular pressure-time integral while maintaining aortic pressure. This resulted in a leftward septal shift with an 11.6% +/- 1.8% decrease in left ventricular septal-to-free wall dimension and a 12.5% +/- 2.4% increase in right ventricular septal-to-free wall dimension, with no changes in right ventricular cardiac output or stroke work. In contrast, right coronary artery occlusion alone produced right heart failure, with a 50% +/- 6% reduction in right ventricular global stroke work and 26% +/- 6% and 27% +/- 3% reductions in cardiac output and right ventricular peak systolic pressure, respectively. This right heart failure persisted during left ventricular unloading with the left ventricular assist device, which resulted in further leftward septal shifting and unchanged but still depressed stroke work and flow output. These findings support the hypothesis that a preexisting pathologic condition is the dominant factor in determining right ventricular function during prosthetic left ventricular support and that direct anatomic interactions play a minor role. PMID- 1921436 TI - Patterns of ductal tissue in coarctation of the aorta in the first three months of life. AB - A possible relationship between recurrence of coarctation and the presence of residual ductal tissue in the aorta was studied by defining the presence and pattern of ductal tissue in aortic segments from 23 patients less than 3 months of age who underwent resection of coarctation of the aorta. The surgical policy was to perform extensive excision of the coarctation, including a wide margin of descending aorta beyond the ductus arteriosus. Histologic examination showed that there was a circumferential sling of ductal tissue extending from the ductus arteriosus and surrounding the aorta at the level of the coarctation shelf in 22 specimens. In 15 of these specimens one or two tonguelike prolongations of ductal tissue extended distally from the circumferential sling and occupied constant positions in the aortic wall; one tonguelike prolongation extended distally below the insertion of the ductus and the other from the circumferential sling opposite the ductal insertion. Incomplete excision of ductal tissue was found in 11 specimens. In relation to the goal of avoiding recurrent coarctation after repair in the early months of life, the possible implications of these findings are discussed, and, in particular, a possible mechanism of recurrence after subclavian flap aortoplasty is proposed. PMID- 1921438 TI - Pulmonary atresia and intact ventricular septum. Definitive repair in the neonatal period. AB - Pulmonary atresia with an intact ventricular septum and a small right ventricle is associated with high mortality and lacks a consensus surgical approach. The results of operations in eight of eleven patients with either pulmonary atresia and an intact ventricular septum or critical pulmonary stenosis, hypoplastic right ventricle, and intact ventricular septum, who were operated on between 1983 and 1989, are presented. Definitive correction was performed via a right ventricular transannular patch with prolonged postoperative prostaglandin E1 infusion. Limiting conditions in using this approach were (1) severely hypoplastic right ventricle, (2) massive tricuspid regurgitation, or (3) right ventricle-dependent coronary artery blood supply. Eleven neonates had the aforementioned diagnoses; eight underwent definitive repair, five successfully. Successful outcome, up to 5 postoperative years, was achieved if the tricuspid valve diameter was greater than or equal to 0.75 cm, or if the tricuspid/mitral valve ratio was greater than or equal to 0.70. Other significant predictors of success were a tripartite right ventricle (p less than 0.006), lack of sinusoids (p less than 0.05), the ratio of the right ventricular internal and external diameters greater than or equal to 0.73 (p less than 0.05), and some contractility (p less than 0.04). Thus we choose a right ventricular transannular patch with long-term prostaglandin E1 infusion for patients with pulmonary atresia and intact ventricular septum if (1) they have a tricuspid valve diameter of 0.75 cm or 70% of the mitral valve size, (2) they have a tripartite right ventricle, (3) they exhibit some right ventricular contractility, (4) they do not have marked tricuspid valve insufficiency, and (5) the coronary arteries do not fill primarily from sinusoids. PMID- 1921437 TI - Prevalence and risk factors of tricuspid regurgitation after correction of tetralogy of Fallot. AB - Tricuspid regurgitation was evaluated in 133 patients with tetralogy of Fallot after corrective operations for a real-time Doppler flow imaging system. Moderate or severe tricuspid regurgitation was found in 15% (10/66) of patients in whom the ventricular septal defect was closed through the right atrium and tricuspid valve, 13% (2/15) through the pulmonary artery, and 25% (13/52) through the right ventricle. These differences were not significant. Right ventricular systolic pressure was significantly higher (66 +/- 27 mm Hg) in patients with moderate or severe tricuspid regurgitation (group A) than in patients with mild or no tricuspid regurgitation (group B) (41 +/- 13 mm Hg) (p less than 0.01). Right ventricular end-diastolic pressure was significantly higher in group A (7.7 +/- 2.2 mm Hg) than in group B (6.1 +/- 2.9 mm Hg) (p less than 0.01). Significant pulmonary regurgitation (angiographic grades 3/4 to 4/4) was more frequent in group A (8/18; 44%) than in group B (14/64; 22%) (p less than 0.05). Residual ventricular septal defect (pulmonary/systemic flow ratio greater than 1.3) was also more frequent in group A (5/18; 28%) than in group B (0/64; 0%) (p less than 0.01). Right ventricular end-diastolic volume was significantly higher in group A (202% +/- 79% of the normal right ventricle) than in group B (158% +/- 38% of normal) (p less than 0.01). Thus significant tricuspid regurgitation was associated with high right ventricular systolic pressure, high right ventricular end-diastolic pressure, and significant pulmonary regurgitation and residual ventricular septal defect, which increased the right ventricular end-diastolic volume. Operative procedure for closing the ventricular septal defect was not related to the development of significant tricuspid regurgitation. PMID- 1921439 TI - Centrifugal pump left heart assist in pediatric cardiac operations. Indication, technique, and results. AB - Twelve children aged 6 days to 12 years had left or common atrial to aortic extracorporeal support with a centrifugal pump after cardiac operations. Left ventricular assist time ranged from 38 to 190 hours. Ten patients were successfully weaned from left ventricular assist device support; four hospital deaths occurred afterward. All six survivors were discharged from the hospital with improved left ventricular function. Although the follow-up time is short and the experience limited, we consider the centrifugal pump type of left ventricular assist device to be a potentially lifesaving treatment modality for selected pediatric patients having cardiac operations. PMID- 1921441 TI - Internal thoracic artery and competitive flow. PMID- 1921440 TI - Biventricular distribution of cold blood cardioplegic solution administered by different retrograde techniques. AB - Although retrograde cardioplegia has been shown to provide adequate overall protection to the myocardium, delivery of cardioplegic solution to the right ventricle and septum is poor. We used an animal model of occlusion of the left anterior descending coronary artery to study the effects of modifying the conditions of retrograde cardioplegia administration on delivery to the right and left ventricles. Adult mongrel dogs (n = 12) were each given five retrograde injections of microsphere-labeled cardioplegic solution at 10-minute intervals. Four injections were made directly into the coronary sinus with ostial balloon occlusion at the following dosages and pressures: (1) 10 ml/kg at 30 mm Hg, (2) 20 ml/kg at 30 mm Hg, (3) 10 ml/kg at 50 mmHg, and (4) 20 ml/kg at 50 mm Hg. A fifth dose (20 ml/kg) was given directly into the right atrium at 50 mm Hg. Delivery of cardioplegic solution to the left and right ventricles was significantly reduced when the right atrial route was compared with the coronary sinus route at the same dosage and pressure (for left ventricle, 6.0% +/- 1.4% versus 22.7% +/- 11.4%/100 gm, p less than 0.001; for right ventricle, 0.7% +/- 0.2% versus 4.1% +/- 0.4%/100 gm, p less than 0.001). Septal delivery was less than that to the anterior and posterior left ventricle (10.4% +/- 1.3% versus 30.3% +/- 3.9% and 27.9% +/- 3.1%/100 gm, p less than 0.0001) for all injections. Delivery to the body of the right ventricle was less than that to the inflow and outflow tracts (1.8% +/- 0.2% versus 4.5% +/- 0.7% and 8.4% +/- 1.5%/100 gm, p less than 0.0001). These results indicate that, in this model, (1) the right atrial route provides less overall cardioplegic solution to both ventricles than direct retrograde coronary sinus cardioplegia and (2) regional abnormalities in distribution with direct retrograde coronary sinus cardioplegia are not affected by changes in the dosage or pressure of injection. PMID- 1921442 TI - Volvulus of the intrathoracic stomach after total esophagectomy. PMID- 1921444 TI - Errors in journal quotations. PMID- 1921443 TI - Bilateral surgical ostial angioplasty of the right and left coronary arteries. PMID- 1921445 TI - A new technique in repair of false femoral aneurysm with a percutaneous balloon catheter for inflow control. PMID- 1921446 TI - Our hematologic heritage. PMID- 1921447 TI - Effects of interleukin 7 on the growth of clonogenic cells in T-cell acute lymphoblastic leukaemia. AB - The effects of the recombinant human cytokines interleukin 2 (IL-2) and IL-7 on the proliferation of T-acute lymphoblastic leukaemia (T-ALL) cells were tested in a clonogenic assay. Highly purified leukaemic cells were obtained by immunomagnetic depletion of mature T cells and fluorescence-activated cell sorting for immature leucocyte markers (CD1, CD10, CD34). Of 9 cases tested, only 3 showed evidence of stimulation by cytokines. One was stimulated by both IL-2 and IL-7, one by IL-2 only, and the third by IL-7 alone. A further case showed proliferation without addition of cytokines. The remaining 5 cases were completely unresponsive. While both IL-2 and IL-7 are capable of stimulating leukaemic cells from some cases of T-ALL, the molecules regulating the proliferation of T-ALL cells in vitro remain to be more fully elucidated. PMID- 1921448 TI - Inhibitory effect of norcantharidin on K562 human myeloid leukemia cells in vitro. AB - Mylabris, the dried body of the Chinese blister beetle, has been used as a Chinese medicinal for over 2000 years. Its active constituent, cantharidin, has antitumor properties and causes leukocytosis. Norcantharidin (NCTD), the demethylated form of cantharidin, is easier to synthesize and is less toxic. NCTD irreversibly reduced the clonogenic efficiency of parental and drug-resistant K562 sublines, with drug-resistant sublines showing greater susceptibility to NCTD than parental cells. NCTD inhibited DNA synthesis by blocking cells at the G2/M phase of the cell cycle. The data suggest that NCTD may be suitable in the treatment of drug-resistant leukemia. PMID- 1921449 TI - Morphologic and flow cytometric analysis of circulating megakaryoblasts in chronic myeloid leukaemia. AB - The immunophenotype (a), ultrastructural features (b) and cell kinetics (c) of circulating megakaryoblasts have been studied in two cases of pure megakaryoblastic and one case of mixed (myeloblastic, megakaryoblastic) cell proliferation in chronic myeloid leukaemia (CML). (a) The blast cells showed early megakaryocyte differentiation antigen (HLA-DR), platelet specific GpIIIa (CD61) and GpIIb-IIIa (CD41) antigens in different percentages. (b) The megakaryoblasts were recognized by the presence of platelet GpIIIa (CD61) demonstrated by an immunoelectron microscopic method. The labelled cells were "lymphocyte-like" megakaryoblasts and cells with features of cytoplasmic maturation (demarcation membranes, alpha granules and vacuoles). (c) Cellular DNA content of the megakaryoblasts was measured by propidium iodide (PI) staining of cells expressing platelet GpIIIa (CD61). Flow cytometric (FC) DNA analysis revealed no aneuploidy and high ploidy (greater than 4N) cell population. In the two cases of pure megakaryoblastic proliferation a high percentage of the megakaryoblasts were in the S-phase, while the non-megakaryoblastic cell fraction showed no elevated S-phase compartment. It is concluded that in CML the circulating megakaryoblasts (1) have a nuclear maturation arrest and accumulation at the level of tetraploid DNA content, (2) surface antigen expression and cytoplasmic organelles show a tendency to mature and (3) in pure megakaryoblastic proliferation the myeloid cells are not in the cell compartment showing high proliferation. PMID- 1921450 TI - Effect of pulsed magnetic fields on leukemia-prone AKR mice. No-effect on mortality through five generations. AB - Leukemia-prone AKR mice were exposed twice a week to a 6 mT, 12 Hz or 460 Hz pulsed magnetic field for 30 min. If we take into account the five consecutive generations of mice, the above exposure actually took place in utero and, or during their life span. There was no difference in the incidence of leukemia or in the actuarial survival curves or in the average spleen or thymus weights. PMID- 1921451 TI - Effect of alpha-IFN on cytokine-induced antigen expression and secretion of TNF, LT and IgM in HCL. AB - In order to investigate the possible mechanisms for the effect of alpha interferon (alpha-IFN) in hairy cell leukaemia (HCL), blood cells from 4 cases were treated in vitro with alpha-IFN, tumour necrosis factor (TNF) and interleukin 2 (IL-2). Changes in the antigen expression, immunoglobulin (Ig) secretion and the production of TNF and lymphotoxin (LT) were investigated. TNF induced expression of CD4 and CD71, increased the intensity of HLA-DR, CD25, CD11c and CD13 expression and decreased both the intensity and frequency of sIg and cIg positivity. alpha-IFN decreased CD25 expression, the tartrate-resistant acid phosphatase activity (TRAP), reduced the TNF-induced CD4 and CD71 expression and antagonized the TNF effect on the Ig expression. Spontaneous TNF or LT production could not be detected in culture supernatants. However, TNF was found to induce LT production, an effect which alpha-IFN antagonized and IL-2 augmented. The reduction of CD25, TNF-induced CD71 and TRAP caused by alpha-IFN seems to represent a deactivation of the activated state of hairy cells (HCs). The failure of alpha-IFN to induce Ig secretion or CD38 expression in HCs speaks against a differentiation induction effect. The LT secretion induced by TNF suggests that other cytokines than TNF might be involved in the proliferation of HCs and that alpha-IFN by blocking the production of LT and perhaps other cytokines causes a growth arrest in HCs. PMID- 1921452 TI - In vivo effect of a large amount of allogeneic granulocytes on reconstitution of hemopoietic cells of irradiated mice. AB - The in vivo effects of allogeneic granulocytes on the reconstitution of splenic and bone marrow CFUs and CFUc numbers were investigated using irradiated mice. When allogeneic granulocytes were intraperitoneally injected into irradiated BDF1 mice (260 rads), the reconstitution of CFUs in both spleen and bone marrow as well as the hematocrit were enhanced, while the reconstitution of splenic or bone marrow CFUc numbers was transiently suppressed and then enhanced. The magnitude of enhancement was dose-dependent. These results suggest that granulocytes injected into irradiated mice might act as enhancing effectors on the in vivo reconstitution of hemopoietic cells. PMID- 1921453 TI - N-ras gene mutations in childhood acute non-lymphoblastic leukemia. AB - In view of the potential role for ras activation in leukemogenesis, we have screened a number of children with acute non-lymphoblastic leukemia (ANLL) for activating point mutations at codons 12, 13 and 61 of the N-ras proto-oncogene using panels of oligonucleotide probes in conjunction with polymerase chain reaction (PCR) gene amplification. In contrast to the frequent occurrence (approximately 30%) of N-ras mutation reported in adult ANLL, 6 of 46 cases (13%) at the time of diagnosis had N-ras mutations involving codons 12 and 13. In these patients we also determine whether presenting clinical symptoms, cellular pathology, karyotype, or eventual outcome distinguished them from the ras negative group. N-ras activation tended to be associated with a higher white blood cell count at diagnosis (mean of 225,000/microliters vs 91,000/microliters) and fewer remissions obtained after 28 days of therapy (3/6, 50% vs 24/32, 75%). It is possible that activation of N-ras oncogene may be involved in the progression of some cases of childhood ANLL. PMID- 1921454 TI - Thymidine-cisplatin vs thymidine-carboplatin interactions in human T-cell acute leukemia. AB - Thymidine is shown to sensitize JM human T-cell acute leukemia cells to cisplatin killing in vitro with dose modifying factors of 1.72, 1.62, and 1.76 at 200, 500, and 1000 micrograms thymidine/ml x 24 h. The magnitude of thymidine-cisplatin sensitization increases with longer thymidine exposures (500 micrograms/ml) up to 16 h but is not further increased at 24 h. For a 25 h thymidine exposure, enhancement is greater for cisplatin (3 micrograms/ml x 1 h) starting 12-24 h into the thymidine exposure vs starting at 0-8 h (p less than or equal to 0.0004). Results are precisely the same for simultaneous studies using carboplatin except that (1) thymidine enhances carboplatin cytotoxicity more than cisplatin killing, (2) enhancement of carboplatin killing varies little with the timing of carboplatin administration during a 25 h thymidine exposure. These findings are discussed relative to their clinical applicability. PMID- 1921455 TI - Activation of the granulocyte-monocyte colony stimulating factor gene in acute myeloid leukaemia cells is not related to gene rearrangement. AB - Several reports have documented that leukaemic blasts produce a number of cytokines among them the granulocyte-monocyte colony stimulating factor (GM-CSF). We analysed the structure of the gene that codes for GM-CSF in 44 acute myeloid leukaemia (AML) cases in an attempt to establish whether the autocrine production of GM-CSF was due to a structural gene alteration. No structural alteration was detected in the GM-CSF gene in any of the 44 cases studied. We, therefore, conclude that the autocrine production of GM-CSF by leukaemia blasts is not dependent on gene rearrangement. PMID- 1921456 TI - Some reasons for the lack of progress in the treatment of acute myelogenous leukemia: a review of three consecutive trials of the treatment of poor prognosis patients. AB - The failure of three consecutive treatment protocols to significantly increase the complete remission rate for poor prognosis newly diagnosed patients with acute myelocytic leukemia led to a detailed investigation of the causes of treatment failure. In the majority of cases treatment failure was attributable to "clinical resistance" to therapy. Upon close examination two types of "clinical resistance" were discernible: the failure of chemotherapy to produce adequate cytotoxic effects ("classical" drug resistance), and treatment failure attributed to the rapid regrowth of leukemia cells subsequent to the substantial killing of leukemia cells by cytotoxic therapy ("biological" resistance). Each form of resistance accounted for one-half of the treatment failures. PMID- 1921457 TI - Autotransplants in leukemia: current state, future progress. AB - Autotransplants in leukemia are controversial; their rationale and results have been questioned. Here we consider several issues central to this debate: (1) Are there convincing data to suggest that more intensive therapy increases cures? (2) Are results post-autotransplant a consequence of the transplant, or do they reflect subject-selection and time-to-treatment (time censoring) biases? (3) Does leukemia relapse after an autotransplant develop from persisting leukemia cells in the subject or the graft? (4) Do autotransplants using hematopoietic stem cells from different sources have distinct outcomes? (5) Are immune-mediated anti leukemia mechanisms likely to prevent relapse after autotransplants? and (6) Can comparably intensive therapy be given without an autotransplant? PMID- 1921458 TI - Interaction of various cytokines with interleukin 2 in the generation of killer cells from human bone marrow: application in purging of leukemia. AB - We have shown that incubation of bone marrow (BM) with interleukin 2 (IL-2) generates activated bone marrow cells (ABM) with potent tumoricidal activity in vitro and in vivo. The present study was carried out to define the interaction of other cytokines with IL-2 in generation of ABM. Our data show that interleukin 1 (IL-1), interferon (IFN)- both gamma and alpha, and tumor necrosis factor (TNF alpha) significantly increased the cytolytic potential of ABM. Interleukin 3, interleukin 4, transforming growth factor-beta and adherent cells were reduced, while granulocyte-macrophage colony-stimulating factor had no influence on the generation of cytolytic activity. IL-1 was enhanced while TNF-alpha depressed the BM progenitor cell activity in vitro. The IL-2-induced purging ability of BM contaminated with leukemic cells was increased by IL-1, TNF-alpha and IFN-gamma. This study shows that biomodulation of BM with combination of cytokines in vitro can be useful in purging a large leukemic burden. PMID- 1921459 TI - Independent clonal origin of T- and B-cell clones in a composite lymphoma. AB - We present a detailed immunohistological and genotypic analysis of an unusual case in which a peripheral T-cell lymphoma, with features of Lennert's and angioimmunoblastic lymphoma, occurred after treatment of a low grade plasmacytoid lymphoma. By analysis of immunoglobulin and T-cell receptor genes, we show that the two diseases had an independent clonal origin at the level of lymphoid commitment. However, by employing a novel polymerase chain reaction-based technique for analysis of B-cell clonality, we show the persistence of a residual minor clonal B-cell population in the subsequent T-cell lymphoma. Only 2 previous cases of composite lymphoma involving B- and T-cell clones have been demonstrated by molecular analysis. This study underlines the immunophenotypic and genotypic heterogeneity of peripheral T-cell lymphomas and illustrates an unusual disease course in which a T-cell lymphoma has arisen in the context of, and perhaps as a consequence of, a B-cell lymphoma. PMID- 1921460 TI - S-phase DNA content and aneuploidy of immunophenotypic defined subpopulations in acute myeloid leukemia determined by multi-parameter flow cytometry. AB - One of the major limitations of DNA flow cytometry (FCM) in hematologic malignancies is the lack of information about the proliferation activity of subpopulations of the heterogeneous bone marrow (BM) compartment. We studied the S-phase DNA content of immunophenotypically defined BM subpopulations (CD2+; CD19+; CD2/CD19+; glycophorin-A+; CD14+; CD13+; CD33+ and CD13/CD33+) in 18 patients with acute myeloid leukemia (AML), including three patients with M6 AML. The results were compared with the findings in twelve normal BM aspirates. The measurements were performed using a special protocol for bivariate FCM of DNA content and surface immunofluorescence (s-IF). In patients with AML the proportion of BM cells expressing the myelomonocytic and monocytic markers (M1-M5 AML) or erythroid marker (M6 AML) was expanded. However, in many patients other subpopulations were 4% or higher permitting the calculation of their S-phase DNA. No essential differences in median S-phase DNA percentages of the distinct subpopulations were observed between normal and leukemic bone marrow though the ranges in AML patients were much wider. These data suggest that AML is not characterized by an increased nor a decreased proliferation activity, but rather by a situation of cell growth independent to the normal regulatory mechanisms. Additional information was obtained upon DNA aneuploidy using CD2+ or CD2/CD19+ cells as an intrinsic DNA standard which allowed us to define differences in the DNA index as small as 2% as aneuploid. This approach appeared suitable for detecting small-degree numerical chromosomal aberrencies, as found by cytogenetics, in 4/6 cases. PMID- 1921461 TI - T-lymphocyte response to cytokines in B-chronic lymphocytic leukemia. AB - The mechanisms underlying abnormal T-cell function in B-chronic lymphocytic leukemia (B-CLL) are unknown. We have studied B-CLL T-cell activation pathways in the rigorous absence of leukemic cells and with controlled numbers of accessory cells present. The responsiveness to added recombinant IL-1 and IL-2 was assessed. We have found that under optimal culture conditions B-CLL T cells had a normal PHA-induced proliferative response in terms of incorporated 3H-thymidine per T cell. Also the capacity of mitomycin-C treated B-CLL monocytes to support autologous T-cell mitogenesis was normal. However, a subtle difference between normal and B-CLL T cells emerged with respect to cytokine responsiveness. While the PHA response of purified normal T cells in the absence of monocytes was augmented by rIL-1, this could not be demonstrated for B-CLL T cells. A much greater degree of augmentation occurred with added rIL-2 in the case of both normal and B-CLL T cells. In the presence of 20% autologous monocytes rIL-1 and rIL-2 had no effect on mitogenesis. We conclude that B-CLL T cells have an abnormal profile of cytokine responsiveness which is consistent with observed abnormalities of subset distribution, and which may contribute to the clinical immunodeficiency in B-CLL. PMID- 1921462 TI - Co-detection of chimeric bcr/abl (target) and beta-actin (control) messenger RNA in individual CFU-GM colonies derived from CML patients using the polymerase chain reaction. AB - In order to quantitate the magnitude of the normal and Philadelphia (Ph') chromosome-positive(+) progenitor cells for various research and clinical settings/studies, we have applied the highly sensitive polymerase chain reaction (PCR) for examining the cells contained in individual hematopoietic colonies for chimeric bcr/abl mRNA, a specific molecular marker for chronic myelogenous leukemia (CML). Thus, individual 14-day CFU-GM colonies, obtained by growth of bone marrow cells from CML patients were removed from methylcellulose cultures and total RNA from each colony was isolated. First-strand complementary DNAs (cDNA) corresponding to all mRNAs in the sample were obtained by using random hexamers in a reverse transcription (RT) reaction. cDNA then served as the substrate in the PCR. To ensure the integrity of the RNA extracted from each colony, beta-actin and bcr/abl cDNA sequences were amplified in the same reaction vessel. Using this method, we have examined the colonies grown from three CML patients and found that 5 out of 5, 9 out of 9 and 8 out of 9 colonies contained a bcr/abl transcript. This method is simple, highly sensitive and should facilitate studies comparing the expression of various oncogenes in normal and leukemic hematopoietic progenitor cells. PMID- 1921463 TI - An ASSEMBLER routine for on-line graphic display and averaging of data acquired on a personal microcomputer. AB - An ASSEMBLER routine is described for data acquisition and "on-line" averaging, artefact rejection and graphic display of data on a personal microcomputer (IBM compatible). The user determines the number of input channels, sampling frequency, number of samples, input range, stimulation frequency (epoch frequency) and the number of epochs to be acquired and averaged. Data from each epoch are scanned in search of saturating artefacts and will be added to previous epochs if none is found. Data are then graphically displayed as voltage versus time before acquiring next epoch. Display options can be defined by the user at run time by means of the keyboard and include: display of last epoch, display of the average, storage screen and refreshing screen after every epoch. High data transfer rates and program speed allows for high stimulation rates in the presence of on line graphic display. The computer then behaves as a multichannel digital oscilloscope with access to large memory buffers, disk storage, high averaging capabilities, artefact rejection and wide potential for data analysis. Its applications to the recording of magnetic and electric evoked responses are illustrated. The program is available from the authors. PMID- 1921464 TI - The electrolytic lesion as a model of spinal cord damage and repair in the adult rat. AB - The utility of the electrolytic lesion as a model of spinal cord injury and repair has been studied in adult Wistar rats. Lesions were created using an 0.1 mA current applied for 30 s in the right hand intermediate zone of the cord, at the level of the 10th thoracic vertebra. After three months, secondary pathological changes at these sites resulted in a variable degree of grey matter atrophy, cavitation, macrophage infiltration and loss of white matter in the dorsolateral funiculus. Functionally, lesioned animals exhibited an incomplete spastic paraparesis of the right hind limb, had normal scores on the inclined plane test, but showed subnormal performance of the right hind limb on the Tarlov scale. Spinal cord neurones dissociated from E14 rat embryos survived for at least 3 months if transplanted into a freshly made electrolytic lesion. However, these implants had no ameliorating effect on the motor deficit induced by electrolytic lesions. It was concluded that the electrolytic lesion represents a useful model for qualitative studies on secondary histopathological changes in the injured cord. Electrolytic lesions also support long-term survival of implanted spinal neurones. However, the possible trophic influence of these implants on motor and sensory tracts could probably be better studied using neonatal, rather than adult rats. PMID- 1921465 TI - Fast cyclic voltammetry can be used to measure stimulated endogenous 5 hydroxytryptamine release in untreated rat brain slices. AB - Fast cyclic voltammetry at a carbon fibre microelectrode was used to monitor the time course of 5-hydroxytryptamine (5-HT) overflow in slices of rat dorsal raphe (DRN) and suprachiasmatic nuclei (SCN), incubated in a brain slice chamber for over 6 h. 5-HT overflow was detected in response to electrical brain stimulation in both regions. Voltammetric evidence showed that the released substance was identical to exogenously applied 5-HT. Overflow was reversibly abolished when Ca2+ was removed from the incubating medium or when TTX was added. Ro4-1284, a reserpine like agent, irreversibly abolished 5-HT overflow from both nuclei. The 5-HT uptake blockers, citalopram, clomipramine, fenfluramine and fluvoxamine dose dependently increased overflow and slowed the rate of removal of 5-HT from the extracellular space in both regions. Benztropine had no effect on overflow in the DRN and SCN whereas it caused a significant increase in dopamine overflow in slices of caudate putamen (CPu). Xylamine had no effect on 5-HT overflow in the DRN and SCN. This evidence indicates that the release of endogenous 5-HT can be measured reliably for long periods and that FCV can be used in brain slices for quantitative studies of 5-HT release and uptake. PMID- 1921466 TI - Methods for recording the jaw-opening reflex to tooth-pulp stimulation in awake cats. AB - Techniques are described for use in awake, unrestrained cats which enable recordings to be made from the digastric muscle, electrical stimuli to be applied to the teeth, and intravenous injections to be made via an indwelling cannula. A headpiece was fixed to the skull of the animal and leads were passed subcutaneously from it to electrodes in the muscle and the teeth. A silicone rubber cannula was inserted into the external jugular vein and connected to an injection port in the headpiece. The headpiece incorporated a miniature 9-way connector which was connected to the electrode leads. PMID- 1921467 TI - A technique for recording from brain-stem neurones in awake, unrestrained cats. AB - A method is described which enables single unit recordings to be made from neurones over a wide area of the brain-stem of awake, unrestrained cats. A small headpiece, made from titanium and acrylic, was fixed to the skull over a craniotomy at pre-set stereotaxic co-ordinates. Between recording sessions the craniotomy was sealed. During recording, a miniature micro-manipulator and adjustable titanium support was screwed into the headpiece and recordings were made with tungsten electrodes. PMID- 1921468 TI - A method for the generation of complex vibrotactile stimuli. AB - A method is described utilizing computer-generated sine wave data and purpose built hardware to generate a complex vibrotactile stimulus. Two sine waves of different frequency were summed to produce a complex waveform with two temporal components, a high frequency component and a low frequency beat component. The computer-generated data points for each of the two component sine waves were downloaded to two banks of static memory in a dual synchronous arbitrary function generator. The data points in memory were fed to two 12-bit digital-to-analogue converters which sent the two analogue sine wave signals to a summing amplifier where the two sine waves were added. This method provides a complex waveform that can be gated on and off, has a fixed frequency ratio of the component sine waves and no phase drift between the component waves. Addition of the separate sine waves in a summing amplifier allows for easy alteration of the amplitude ratio of the sine waves. The output of the summing amplifier is sent to a feedback controlled mechanical stimulator, thereby allowing the stimulus to be presented to the skin of human subjects and experimental animals. PMID- 1921469 TI - Cultivation of rat fetal spinal cord slices in a semi-solid medium: a new approach to studying axonal outgrowth and regeneration. AB - A soft agar culture system was used for the cultivation of spinal cord slices with the purpose of improving the evaluation of the dynamics of axonal outgrowth and development. Slices of the spinal cord of 15-day-old fetal Wistar rats were cultured in a 0.5% agar culture medium. The sprouting and outgrowth of axons from the slices was observed at 6-24-h intervals. The morphology and growth rates of axons could be easily investigated by light microscopy. Quantification of growth parameters of individual neurites is made easy because no cells migrate out of the slices, so that the outgrowth is not masked by migrating neurons, fibroblasts, glial cells etc. The axons had well-developed growth cones, comparable to those observed in liquid medium; the daily growth rate was on average 318 microns during the 6 days of observation, with a maximum of 1050 microns per day. Back-labelling with a fluorescent dye (DiI) indicated that the longest neurites originated from motoneurons. Our experiments show that axons can develop and grow in a soft agar medium without the need for adding any growth promoting factor or substrate molecule. PMID- 1921470 TI - Potential errors due to aliasing in digital video analysis of quantitative autoradiography. AB - Digital image analysis of quantitative autoradiographic (QAR) films is widely used in neuroscience applications. Unless proper precautions are taken when autoradiographic images are converted to digital form they can be inadvertently modified by improper application of the sampling process. This type of modification is termed aliasing error and can cause nonexistent structures to appear in the reconstructed digital image, changing the apparent optical density values of the data. The theoretical basis of aliasing error is presented, along with examples of aliasing from optical resolution test patterns and 2 deoxy[14C]glucose (2-DG) experimental QAR images. We show that aliasing can change the apparent shape of structures, as well as the derived values obtained from QAR experiments. In an example with experimental 2-DG images, aliasing in the cerebellar cortex consistently underestimates tissue radioactivity levels in gray matter (P less than 0.001) and overestimates levels in adjacent white matter (P less than 0.001). Additional data transformations, such as the equations used for blood flow or glucose utilization, can, somewhat unpredictably, accentuate the errors introduced by aliasing. We present a discussion of the autoradiographic image features and electronic design that play a role in introducing aliasing errors and means by which aliasing can be recognized and minimized. PMID- 1921471 TI - Manufacture of sharpened microelectrodes from varnished wire. PMID- 1921473 TI - Glutathione redox cycle is an important defense system of endothelial cells against chronic hyperoxia. AB - Exposure of cultured pulmonary artery endothelial cells to 95% O2 resulted in the following sequence of events: decrease in [3H]thymidine incorporation after 24 h; increase of intracellular glutathione (GSH) and loss of cellular protein after 48 h; increase of spontaneous and decrease of provoked prostacyclin formation as well as increased release of cellular LDH after 72 h. This oxygen toxicity model was used to study the following 2 questions. (1) What is the relative importance of the GSH redox cycle compared to catalase as antioxidative defense against hyperoxia? Endothelial cells were grown in selenium-depleted medium to inhibit glutathione peroxidase activity. Endothelial GSH biosynthesis was inhibited by buthionine sulfoximine. Catalase activity was reduced by aminotriazole. Endothelial cells with an impaired GSH redox cycle were easily killed by hyperoxia within 24 h, while inhibition of catalase did not enhance the susceptibility of endothelial cells to hyperoxia. (2) Can endothelial GSH content be increased by exogenous sulfhydryl reagents and does this result in an increase of endothelial cells' resistance to hyperoxia? Exogenous GSH, N-acetylcysteine, cysteine, and L-2-oxothiazolidine-4-carboxylate (L-2-oxo) increased intracellular GSH. All sulfhydryl reagents (with the exception of L-2-oxo) protected endothelial cells from hyperoxia. Concentrations of exogenous GSH and N acetylcysteine that did not increase intracellular GSH reduced hyperoxia-induced endothelial cell injury. Thus the capacity of the GSH redox cycle rather than intracellular GSH levels or catalase determines endothelial cells' resistance to hyperoxia. PMID- 1921475 TI - A rational approach to the management of lymphedema. AB - Because of the complexity of peripheral lymphedema disorders and the variability in severity and clinical appearance, no standardized management plan of these patients is universally accepted. Based on our lengthy experience, we attempt in this report to outline a protocol for "staging" and managing lymphedema including the role of microsurgical lymphatic angioplastic shunts. PMID- 1921474 TI - Inflammatory mediators and cellular infiltration of the lungs in a guinea pig model of the late asthmatic reaction. AB - Alterations in cell numbers, vascular permeability, and concentrations of various inflammatory mediators in the lung were measured in a guinea pig model of the late asthmatic reaction. Animals sensitized by inhalation of ovalbumin were challenged with an aerosol of ovalbumin or saline, and bronchoalveolar lavage fluid (BALF) and peripheral blood were collected after periods ranging from 5 min to 72 h. Increased vascular leakage within the lungs was indicated by elevated BALF/plasma albumin ratios at all time points, and was maximal 6 h after challenge. There were increased numbers of eosinophils in BALF by 6 h after challenge and they remained elevated at least until 72 h. A corresponding increase in the proportion of blood leukocytes represented by eosinophils was observed at 6 and 17 h, which suggests that these cells may be drawn to the lung following their release into the circulation, but by 72 h the proportion in blood had returned to normal. A transitory neutrophilia was evident in BALF and blood 6 h after allergen exposure, but there were no allergen-induced changes in BALF numbers of macrophages, lymphocytes, epithelial cells, or mast cells (as assessed by concentrations of cell-associated histamine). beta-Glucuronidase activity was significantly increased in BALF of guinea pigs at 2 h and 17 h following challenge. The degree to which eicosanoids can be recovered in BALF was investigated by instilling a range of tritiated compounds into the lungs of normal guinea pigs at the time of lavage. Ratio high-performance liquid chromatography revealed that there had been little metabolism of the eicosanoids recovered in BALF. However, there was evidence for a rapid removal of these mediators from the lung, a process which will militate against their accurate quantitation in BALF. Histamine, prostaglandin D2, and thromboxane B2 were detected in BALF but did not differ between treatment groups, and levels showed no simple relationship with the other inflammatory changes measured. PMID- 1921472 TI - Endothelium-derived relaxing factor and the pulmonary circulation. AB - Endothelium-derived relaxing factor (EDRF) is probably identical to nitric oxide (NO) and is released by the vascular endothelium both in the basal unstimulated state and in response to a wide range of physical and chemical stimuli. Since it was first described 10 years ago, evidence is accumulating that it is an important modulator of vascular smooth muscle tone. EDRF acts on the pulmonary vascular bed as on the systemic circulation. EDRF release to pharmacologic stimuli is impaired in pulmonary arteries from patients with chronic hypoxemia. This impairment is associated with severity of respiratory failure and of structural change of vessel walls. Disturbance of EDRF activity may be important in the pathophysiology of pulmonary vascular disease. This brief review describes the current status of experimental studies concerning the possible role of EDRF on the pulmonary circulation in normal conditions and in the pathogenesis of pulmonary hypertension. PMID- 1921476 TI - Lymphatic arteriopathy: damage to the wall of the canine femoral artery after lymphatic blockade. AB - The effect of lymph stasis on the histological, biochemical, and elastic properties of the femoral artery were studied after regional lymphatic blockade in 36 dogs. Dogs were sacrificed 4-21 days after operation. Histologic changes of the femoral arterial wall (interstitial edema, degeneration in the muscle layer or media, thickened adventitia with dilated lymph vessels, and fibrosis) developed after regional lymphatic blockade. Characteristic metabolic alterations of the arterial wall (anaerobic catabolism of carbohydrate, increased lactate and glycosamine content) accompanied the morphological changes. Distensibility of the femoral artery decreased and greater elastic stiffness developed after regional lymphatic blockade. These results in conjunction with other experimental and clinical data support the concept that insufficient lymphatic transport within the blood vessel wall may contribute to the genesis and progression of arteriopathies. PMID- 1921478 TI - Lymphedema of the leg associated with rheumatoid arthritis. AB - A 14-year-old boy with a two year history of seronegative rheumatoid arthritis developed left leg lymphedema and subsequently a severe episode of lymphangitis. The diagnosis of "rheumatoid lymphedema" was confirmed by lymphscintigraphy and conventional lymphography. Treatment consisted of bedrest and antibiotic drugs. When the signs of inflammation had subsided, therapy with corticosteroids was started with improvement of both joint pain and leg swelling. Whereas lymphedema associated with rheumatoid arthritis has been described in the upper limb of adults, to our knowledge this is the first report of the coexistent condition in the lower leg of a child. PMID- 1921477 TI - Immunoelectron microscopy of cell populations in regional and central lymph of sheep. AB - The immunoreactivity and the ultrastructural localization of monoclonal anti sheep lymphocyte antibodies conjugated with colloidal gold particles were examined in free-floating cells of sheep central lymph from the thoracic duct, postnodal lymph draining either the popliteal nodes or the mesenteric nodes, and prenodal lymph draining the pregnant uterus. The monoclonal antibodies used in this study were SBU-T1 (CD5), SBU-T4 (CD4), SBU-T8 (CD8), SBU-II (anti DR antibody), and E53 which are reported to be sheep homologues of human T1, T4, T8, HLA-DR, and pan B cell antibodies, respectively. Colloidal gold particles were evenly distributed or segmentally aggregated on the surfaces of lymphocytes and macrophages incubated with monoclonal antibodies and in vesicles in the cytoplasm of anti DR antibody labeled macrophages. Not only did CD5 labeled cells show a high percentage in each regional lymph examined, but the percentage of CD4 labeled cells was consistently higher than that of CD8 labeled cells. Moreover, the immunoreactivity of CD8 labeled cells was specific among lymph from the different regions. The sum of the percentages of CD4 and CD8 labeled cells was less than the percentage of CD5 labeled cells, indicating the presence of a minor T cell subpopulation which was CD5+, CD4-, and CD8-. A characteristic finding was a high percentage of CD8 labeled cells and many abnormal eosinophils in uterine prenodal lymph in pregnant sheep. Taken together the results showed that variously labeled immunoreactive cells are distributed somewhat differently in lymph derived from different organ sites. PMID- 1921479 TI - Use of autologous interposition vein graft in management of lymphedema: preliminary experimental and clinical observations. AB - We report preliminary experimental studies in rats and rabbits together with clinical observations in 39 patients with chronic lymphedema undergoing interposition autologous lymphatic-venous-lymphatic (LVL) anastomoses. This microsurgical operative technique is an alternative to other lymphatic shunting methods particularly where venous disease coexists in the same limb and where direct lymphatic-venous bypass is accordingly inappropriate. Preoperative diagnostic evaluation including lymphatic and venous isotopic scintigraphy, Doppler venous flow metrics and pressure manometry play an essential role in delineating the status of both the lymphatic and venous systems and in determining which microsurgical procedure, if any, is indicated. Our microsurgical method consists of inserting suitably large and lengthy autologous venous grafts between lymphatic collectors above and below the site of blockage to lymph flow. The data demonstrate the feasibility of the LVL technique experimentally and in 39 patients with obstructive lymphedema (either arm or leg). Using LVL shunt, improvement was seen in both limb function and edema, and in some, edema regression was permanent for as long as 5 years. PMID- 1921480 TI - Abdominal lymph flow response to intraperitoneal fluid in awake sheep. AB - Lymphatic vessels are important in draining excess fluid from the abdominal space and preventing ascites. In sheep, diaphragmatic lymph vessels draining the abdominal space run to the caudal mediastinal lymph node and efferent vessels from the node drain into veins in the neck. To estimate the lymph flow response to excess intraperitoneal fluid in sheep, we cannulated a caudal mediastinal node efferent lymphatic in 5 sheep. After the sheep recovered from the surgery, the lymph flow (QL) was 154 +/- 161 (SD) microliters/min and the lymph protein concentration (CL) was 3.7 +/- 9 g/dl. Lymph flow decreased linearly with increases in lymphatic outflow pressure greater than 6 cmH2O. From this linear QL vs. outflow pressure relationship, we estimated the effective pressure driving lymph flow as the outflow pressure at which QL = 0. At baseline, the driving pressure was 24.7 +/- 14.0 cmH2O. After we infused Ringers solution (10% body weight) into the abdominal space, QL increased significantly to 7.0 +/- 4.1 times baseline and CL decreased significantly to 0.7 +/- 0.6 g/dl. Although the abdominal pressure increased significantly from 10.6 +/- 2.8 cmH2O to 15.8 +/- 2.1 cmH2O, we found no increase in lymphatic driving pressure. PMID- 1921481 TI - Light and electron microscopy of the structural organization of the tissue lymphatic fluid drainage system in the mesentery: an experimental study. AB - Supplementing vital microscopy and histophysiology, we examined using combined light and electron microscopy the tissue fluid-lymphatic drainage system of the mesentery isolated from guinea pigs, rabbits, and tree shrews. In silver impregnated tissue, different types of lymphatics and blood vessels were able to be distinguished along with argyrophilic and argyrophobic structures in the connective tissue. Some initial lymphatic pathways were interrupted by non endothelialized tissue zones thus forming separate but discrete vascular "islands". After carbon labeling of the lymphatic collectors, carbon particles were seen to escape from the initial lymphatic lumen at various sites. Electron microscopy revealed wide apertures in the lymphatic endothelial cells of these microvessels. These morphological findings support the concept of an "open" prelymphatic-lymphatic system in the mesentery. The special histometrical features exhibited by a flat membranous organ like the mesentery are discussed in terms of physiologic function of mesenteric tissue fluid transport. PMID- 1921482 TI - Early experience with percutaneous cholecystolithotomy. AB - Percutaneous cholecystolithotomy should be added to the list of alternatives to elective open cholecystectomy for the management of patients with gallstones. Our initial experience with percutaneous cholecystolithotomy in 13 patients (7 men and 6 women who ranged in age from 47 to 83 years) demonstrated that the procedure could be accomplished successfully with acceptable morbidity and no mortality. After a mean duration of follow-up of 10.7 months, only one patient had recurrent cholelithiasis. Because of rapid changes in the therapeutic approach to patients with cholelithiasis, percutaneous cholecystolithotomy may seldom be used. PMID- 1921483 TI - Effect of inhibition of converting enzyme on renal hemodynamics and sodium management in polycystic kidney disease. AB - We compared the tubular transport of sodium and the erythrocyte sodium-lithium countertransport activity in hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) and in normotensive control subjects. In addition, we assessed the effects of inhibition of converting enzyme on renal hemodynamics and sodium excretion in hypertensive patients with ADPKD to provide information on mechanisms responsible for the increased renal vascular resistance and filtration fraction and the adjustment of the pressure-natriuresis relationship during saline expansion, observed in patients with ADPKD, hypertension, and preserved renal function. In comparison with normotensive control subjects, the hypertensive patients with ADPKD had lower renal plasma flows, higher renal vascular resistances and filtration fractions, and similar proximal and distal fractional reabsorptions of sodium. The administration of enalapril resulted in significant increases in the renal plasma flow and significant reductions in mean arterial pressure, renal vascular resistance, and filtration fraction, but the glomerular filtration rate remained unchanged. Despite the significant reduction in mean arterial pressure during inhibition of converting enzyme, the distal fractional reabsorption of sodium decreased while the total fractional excretion of sodium remained unchanged or increased slightly. No significant differences were detected between the normotensive control subjects and the hypertensive patients with ADPKD in erythrocyte sodium lithium countertransport activity, plasma renin activity, plasma aldosterone concentration, or atrial natriuretic factor. These results suggest that the renal renin-angiotensin system plays a central role in the alterations in renal hemodynamics and sodium management associated with the development of hypertension in ADPKD. PMID- 1921484 TI - Omega-3 polyunsaturated fatty acids: a potential new treatment of immune renal disease. AB - Omega-3 polyunsaturated fatty acids are among new treatments being tested for efficacy in immune renal disease. The principal omega-3 polyunsaturated fatty acids are eicosapentaenoic acid and docosahexaenoic acid. They are derived from alpha-linolenic acid, which is found mainly in marine lipids. Eicosapentaenoic acid and docosahexaenoic acid undergo biologic transformation into trienoic eicosanoids that alter inflammatory mediators and vascular reactivity, both of which are important in the pathogenesis of certain glomerular immune diseases. Investigators have shown that proteinuria was prevented and survival was prolonged in autoimmune models of nephritis after dietary supplementation with fish oil. Furthermore, vascular damage may be modified by the influence of eicosapentaenoic acid and docosahexaenoic acid on blood rheology, aggregation of platelets, and plasma lipids. In short-term clinical studies, omega-3 polyunsaturated fatty acids seem to diminish cyclosporine-induced nephrotoxicity and the attendant complication of hypertension, to inhibit inflammatory and atherogenic mechanisms in lupus nephritis, and to preserve renal function and reduce proteinuria in IgA nephropathy. Long-term clinical trials for testing fish oil in these three clinical conditions are under way to confirm or refute these apparent beneficial therapeutic results. PMID- 1921485 TI - Localization of lesions of the oculomotor nerve: recent concepts. AB - The anatomic features of the third cranial nerve (the oculomotor nerve) and the localization of lesions that affect it are reviewed. Recent considerations of the organization of the oculomotor fascicles in the ventral mesencephalon, the superior and inferior divisional palsies localized proximal to the cavernous sinus, and the possibility of the localization of ischemic oculomotor palsies to the mesencephalon rather than a peripheral site are emphasized. The characteristic manifestations of nuclear lesions (unilateral palsy of the third cranial nerve, weakness of the ipsilateral and contralateral superior rectus muscles, and bilateral incomplete ptosis) are described, as are other variations of nuclear involvement. Although proptosis is typically associated with orbital masses, it may also result from lesions of the cavernous sinus or (rarely) an intracranial lesion. Metastatic orbital tumors often are the first evidence of systemic spread in patients with cancer; infiltrative and mass lesions are the most common. Aberrant regeneration of the oculomotor nerve may occur months to years after the occurrence of an oculomotor lesion. PMID- 1921486 TI - Epidural abscess associated with intravenous drug abuse in a pregnant patient. AB - The association between intravenous drug abuse and epidural abscess is well known; however, this association has not previously been reported in a pregnant patient. The classic manifestation of epidural abscess is a febrile patient with back pain that progresses rapidly to radicular pain, spinal cord dysfunction, weakness, and then complete paralysis. Although this condition is rare during pregnancy, these serious complications necessitate prompt diagnosis and intervention. If spinal infection is suspected, magnetic resonance imaging should be performed immediately. After epidural abscess is diagnosed, emergent decompressive laminectomy and appropriate antibiotic coverage are necessary. Herein we describe a 27-year-old pregnant patient with epidural abscess probably related to use of contaminated needles for intravenous administration of drugs and subsequent hematologic spread of staphylococci to the epidural space. The differential diagnosis of epidural abscess can be difficult, and management options must consider the well-being of both the mother and the fetus. PMID- 1921487 TI - Pyopneumopericardium attributed to an esophagopericardial fistula: report of a survivor and review of the literature. AB - Herein we describe a case of pyopneumopericardium that resulted from formation of an acquired esophagopericardial fistula in a patient with silent, benign esophageal ulcer disease. Atypical features on initial examination suggested congestive heart failure or a pneumonic process (or both). The delayed development of pneumopericardium disclosed on a chest roentgenogram led to the clinical recognition of the esophagopericardial fistula. Subsequent emergent pericardiocentesis relieved cardiac tamponade and enabled us to diagnose pyopneumopericardium. A radiographic contrast study with use of meglumine diatrizoate revealed the site of the fistula in the midesophagus. The esophagopericardial fistula was surgically closed, and our patient had a good final result. Formation of an esophagopericardial fistula is a relatively uncommon finding; of the 60 previously reported cases, only 10 patients have survived. As illustrated in the current case, early diagnosis and treatment, including pericardial drainage and intense antibiotic therapy followed by a well planned operative closure of the fistula, are paramount for the successful management of esophagopericardial fistulas. PMID- 1921488 TI - Semerau-Siemianowski--Polish cardiologist. PMID- 1921489 TI - The penicillins. AB - The penicillin family of antibiotics remains an important part of our antimicrobial armamentarium. In general, these agents have bactericidal activity, excellent distribution throughout the body, low toxicity, and efficacy against infections caused by susceptible bacteria. The initial introduction of aqueous penicillin G for treatment of streptococcal and staphylococcal infections was an important pharmacologic landmark. The emergence of penicillinase-producing Staphylococcus aureus prompted the development of the penicillinase-resistant penicillins (for example, methicillin, oxacillin, and nafcillin), in which an acyl side chain prevented disruption of the beta-lactam [corrected] ring. Subsequently, the aminopenicillins (such as ampicillin and amoxicillin) were developed because of the need for gram-negative antimicrobial activity. Their spectrum included Escherichia coli, Proteus mirabilis, Shigella Salmonella, Listeria, Haemophilus, and Neisseria. The search for a penicillin with additional antimicrobial activity against the Enterobacteriaceae and Pseudomonas aeruginosa led to the development of the carboxypenicillins (carbenicillin, ticarcillin, and temocillin) and the ureidopenicillins (mezlocillin, azlocillin, piperacillin, and apalcillin). Finally, the combination of a beta-lactamase inhibitor (clavulanic acid or sulbactam) and an aminopenicillin or ticarcillin has further extended their antibacterial spectra. The development of an ideal penicillin that is rapidly bactericidal, nonsensitizing, nontoxic, bioavailable, resistant to beta lactamase, and without inoculum effect and that has a high affinity for penicillin-binding proteins remains the goal. PMID- 1921490 TI - Cephalosporin antimicrobial agents and related compounds. AB - Cephalosporins are broad-spectrum antimicrobial agents that are often used empirically to treat suspected bacterial infections and also to treat culture proven infections due to selected gram-positive and gram-negative microorganisms. Cephalosporins differ widely in their spectrum of activity, susceptibility to beta-lactamases, serum half-life, and penetration of the central nervous system. In general, the first-generation and second-generation agents are most active against staphylococci and streptococci, and the third-generation agents are most active against the Enterobacteriaceae and Pseudomonas. As a group, cephalosporins have a favorable profile of toxicity in comparison with other antimicrobial agents. The development of bacterial resistance has affected all steps of the cephalosporin mechanism of action, including production of beta-lactamases, alterations in penicillin-binding proteins, and modification of the cell wall. New cephalosporins are among the most expensive pharmaceutical agents in use today. Maintaining expertise in the choice and use of these agents will remain a challenge to physicians as additional investigational cephalosporins continue to be developed and introduced into clinical practice. PMID- 1921491 TI - Imipenem. AB - Imipenem is the first of a new class of beta-lactam antibiotics, the carbapenems, to be released for clinical use. It has the broadest antibacterial activity of all antibiotics available for systemic use in humans. It is active against streptococci, methicillin-sensitive staphylococci, Neisseria, Haemophilus, anaerobes, and the common aerobic gram-negative nosocomial pathogens including Pseudomonas. Resistance to imipenem may emerge during treatment of P. aeruginosa infections, as has occurred with other beta-lactam agents; P. maltophilia and P. cepacia are typically resistant to it. Like the penicillins, imipenem has inhibitory activity against enterococci. Daily doses may range from 500 mg to 1 g, every 6 to 8 hours, in patients with normal renal function. The principal toxic effects have been nausea and vomiting, which occur during intravenous infusion, and seizures, which develop in 1 to 3% of treated patients and are likely to occur in the setting of renal insufficiency and underlying disease of the central nervous system. Imipenem should be considered for treatment of mixed bacterial infections and treatment of resistant aerobic gram-negative bacteria that are not susceptible to other beta-lactam agents. In addition to provoking unnecessary toxicity, indiscriminate use of this agent will promote dissemination of resistance against it. PMID- 1921492 TI - A new drug for treatment of essential tremor? Time will tell. PMID- 1921493 TI - Nocturnal nasal ventilation. PMID- 1921494 TI - Dr. James C. Masson and Mayo. PMID- 1921495 TI - Treatment of essential tremor with methazolamide. AB - We treated 28 patients (16 women and 12 men) who had essential tremor with methazolamide. Their median age was 69 years (range, 34 to 89 years), and the median duration of tremor was 16 years (range, less than 1 to 69 years). Fifteen cases were familial and 13 were sporadic. Improvement in 10 patients who continued taking the drug ranged from moderate to complete relief. In addition, four patients had marked improvement and two had moderate improvement but discontinued use of the drug because of side effects. Five patients with a mild response and seven with no response also discontinued methazolamide therapy. The maximal mean daily dose was 203 mg for all patients and 129 mg (maintenance dose) for the patients who continued taking the drug. Side effects consisted primarily of somnolence, nausea, epigastric discomfort, anorexia, paresthesias, and numbness. No aplastic anemia was noted in any of the patients. The median duration of follow-up was 6 months (range, 10 weeks to 29 months). The therapeutic effect seemed unrelated to a family history of tremor, the effect of alcohol, or the responsiveness to propranolol or primidone. Methazolamide may be an effective drug in the treatment of some patients with essential tremor, particularly those with head and voice tremor. PMID- 1921496 TI - Mayo alumni reunions. PMID- 1921497 TI - Lipoprotein analysis in the evaluation of chest pain in the emergency department. AB - Apolipoproteins were measured in a prospective blinded fashion in blood specimens from patients with chest pain in the emergency department. A definitive diagnosis for the chest pain (non-cardiac-related in 32% and angina or myocardial infarction in 68%) was available in 136 of the 162 patients originally enrolled in the study. Logistic regression and multivariate analysis failed to show any usefulness of apolipoprotein determinations in distinguishing patients with cardiac ischemia from those without it. The clinician's initial impression of the chest pain, the electrocardiogram, a history of previous angina, myocardial infarction, or peripheral atherosclerosis, and male sex were strongly associated with the final diagnosis. We conclude that, although apolipoprotein analysis has proved useful in epidemiologic studies, the most reliable indicators of ischemic pain remain the medical history, the electrocardiogram, and the clinician's overall initial impression. PMID- 1921498 TI - Eosinophilic fasciitis associated with use of L-tryptophan: a case-control study and comparison of clinical and histopathologic features. AB - We investigated the relationship between use of L-tryptophan and development of eosinophilic fasciitis by two methods: a retrospective patient survey and a case control study of patients with eosinophilic fasciitis diagnosed at the Mayo Clinic between 1977 and 1989. Before 1986, no traceable patients with eosinophilic fasciitis had taken L-tryptophan. Between Jan. 1, 1986, and July 31, 1989, 8 of 34 patients had ingested L-tryptophan (P less than 0.001). In the case control study, traceable patients with eosinophilic fasciitis were matched with patients who had systemic sclerosis or rheumatoid arthritis and healthy control subjects who had undergone a general medical examination. Of the 60 matched control subjects, 2 had used L-tryptophan. Thus, the odds ratio was 19, indicating a 19-fold greater likelihood of use of L-tryptophan in patients with eosinophilic fasciitis than in the control group. A retrospective assessment of clinical features, response to treatment, and blinded review of biopsy specimens of skin and fascia in patients who had eosinophilic fasciitis with or without exposure to L-tryptophan disclosed no significant differences in the two groups. This retrospective study confirms a strong association between consumption of L tryptophan and development of eosinophilic fasciitis in some patients. No clinical or histopathologic features were detected that distinguished this disorder on the basis of previous exposure to L-tryptophan. PMID- 1921499 TI - Spectrum of results after treatment of rhinophyma with the carbon dioxide laser. AB - Between 1986 and 1989, 30 patients with rhinophyma were treated with the carbon dioxide (CO2) laser at our institution. The duration of disease ranged from 1 to 20 years, and the duration of follow-up ranged from 1 to 4 years. All the patients were men, and all had fair skin (predominantly type I skin); their mean age was 63 years. Patients with minor and moderate rhinophyma were treated with CO2 laser vaporization only, whereas patients with major rhinophyma were treated sequentially with CO2 laser excision and then vaporization. A spectrum of long term results is presented. Although dilated pores developed in many patients, no re-treatment with the CO2 laser was necessary. In one patient each, leukoderma, unilateral alar lift, and mild hypertrophic scarring developed. In general, use of the CO2 laser is effective for precise decortication of rhinophyma in an office-outpatient setting. PMID- 1921500 TI - Amyotrophic lateral sclerosis and life-sustaining therapy: patients' desires for information, participation in decision making, and life-sustaining therapy. AB - To identify the wishes of patients with amyotrophic lateral sclerosis (ALS) for information, participation in decision making, and life-sustaining therapy and to determine whether these wishes are stable over time, we conducted a prospective survey (baseline and 6-month follow-up interviews) of 38 consecutive patients with an established diagnosis of ALS at the University of Chicago Motor Neuron Disease Clinic. Demographic data, clinical stage of ALS, illness experience, wishes for information, and desires for participating in decisions about life sustaining therapy were elicited. Patients readily expressed their wishes for specific information on communication aids and ventilator care for respiratory failure. Demographic, socioeconomic, and clinical characteristics did not predict patients' desires for information and decision making. The preferences for information and participation in decisions were stable during the 6-month study period, whereas preferences for cardiopulmonary resuscitation in two hypothetical circumstances were less stable. Changes were unrelated to demographic or clinical characteristics of the patients. Because many patients with ALS change their preferences for life-sustaining therapy, advance directives for end-of-life care must be reevaluated periodically. PMID- 1921501 TI - Granulomatous hepatitis: a retrospective review of 88 cases at the Mayo Clinic. AB - Although several studies have shown that sarcoidosis and tuberculosis are the most common causes of granulomatous hepatitis (GH), these studies were biased because results of unselected liver biopsies and autopsy reports were included. We reviewed the medical records of patients diagnosed with GH at the Mayo Clinic between September 1976 and October 1985 for the current study. Our study group consisted of 45 women and 43 men (mean age, 54.2 years). Overall, 65 patients (74%) were symptomatic; the rest had only liver enzyme abnormalities. The mean duration of symptoms was 19.1 months. Assessment of these patients and a comprehensive workup for infectious agents or other causes revealed idiopathic GH confined to the liver in 50%, sarcoidosis with confirmed extrahepatic disease in 22%, drug-related GH in 6%, tuberculosis in 3%, and other causes in 19%. Our study found a much higher frequency of idiopathic GH than previously published reports, and it represents the largest number of cases of idiopathic liver granulomas reported in a single series. PMID- 1921502 TI - Pulmonary hypertension and familial Mediterranean fever: a previously unrecognized association. AB - Familial Mediterranean fever is an autosomal recessive inherited disorder characterized by recurrent episodes of fever accompanied by inflammation of the peritoneum, pleura, synovial membranes, and skin. The disorder predominantly affects persons of Mediterranean origin. The most serious complication of the disease is amyloidosis, which is the cause of death in a substantial proportion of adult patients with the disorder. Only one previous report has described pulmonary hypertension in a patient with systemic amyloidosis associated with multiple myeloma. Herein we describe the first known occurrence of pulmonary hypertension due to pulmonary amyloidosis in a 48-year-old woman with familial Mediterranean fever. Postmortem examination showed extensive deposits of amyloid in the pulmonary vessels, alveolar capillary walls, and myocardium, which explained the hypoxia, hypotension, and terminal cardiac arrhythmias that were the immediate cause of death in this patient. PMID- 1921503 TI - Cryptococcal meningitis manifesting as epilepsia partialis continua of the abdomen. AB - We report a case of epilepsia partialis continua that primarily involved the abdominal muscles. Thorough assessment ultimately showed that the condition was due to cryptococcal meningitis. Surface electrode electromyography and electroencephalography were helpful in analyzing this unusual epileptic phenomenon. An 8-week treatment regimen of amphotericin B and a 30-day course of 5-fluorocytosine abolished the epilepsia partialis continua and cured the meningitis. This case should alert physicians to the fact that patients with epilepsia partialis continua may have clonic movements of only the trunk and that the spectrum of neurologic manifestations of cryptococcal infection must now include this seizure disorder. PMID- 1921505 TI - Medical mythology: Pallas Athena (Minerva). PMID- 1921504 TI - Laboratory tests used to guide antimicrobial therapy. AB - Laboratory tests that are usually considered helpful in guiding antimicrobial therapy include antimicrobial agent susceptibility tests, determination of bacterial production of beta-lactamase, and assay of specific antimicrobial levels in serum and other body fluids. Susceptibility tests should be performed primarily on clinically significant isolates from critical specimens (such as blood or other normally sterile body fluids or tissues) with use of standardized methods established by the National Committee for Clinical Laboratory Standards. Reporting of results should be selective so that clinicians are encouraged to use the least expensive but useful agent in a group--for example, first-generation rather than third-generation cephalosporins. Because standardized methods are not available for assays of serum inhibitory and bactericidal activity, the accuracy and clinical utility of these tests are as yet undetermined. Determination of bacterial resistance to antimicrobial agents is the most important goal of susceptibility testing. Special methods are needed to detect methicillin resistant staphylococci, high-level aminoglycoside- and glycopeptide-resistant enterococci, and antimicrobial-resistant strains of Neisseria gonorrhoeae, Streptococcus pneumoniae, and Haemophilus influenzae. Accurate measurement of serum concentrations of antimicrobial agents is important to ensure that therapeutic levels have been obtained and to avoid excessive levels of potentially toxic agents such as aminoglycosides and glycopeptides, especially when renal function is compromised. PMID- 1921507 TI - Chest pain in the emergency department: uncertainty and the test of time. PMID- 1921508 TI - The Hippocratic ethic in a contemporary era of clinical uncertainty. PMID- 1921506 TI - Survivors of acute myocardial infarction: who is at risk for sudden cardiac death? AB - Coronary artery disease is the leading cause of death in the United States. Approximately half of the deaths attributable to coronary artery disease are sudden cardiac deaths. A logical approach to prevention of sudden death is to identify those who are at risk and then to initiate effective therapy. Left ventricular dysfunction, frequent ventricular ectopic activity, nonsustained ventricular tachycardia, and late potentials have been identified as markers for increased risk of sudden cardiac death. The sensitivity and specificity of these risk factors vary, and the positive predictive power is less than satisfactory. The value of invasive electrophysiologic testing for risk stratification in the general postinfarction patient population remains unclear. In addition to these diagnostic difficulties, prevention of sudden death also has been limited by imperfect efficacy and potential lethal effects of the currently available antiarrhythmic agents. Automatic implantable defibrillators are effective for aborting sudden death; however, the potential for more general use of automatic defibrillators in asymptomatic but high-risk postinfarction patients has not been evaluated. PMID- 1921509 TI - Utility of red cell mass determination. PMID- 1921510 TI - Differential diagnosis of spontaneous renal rupture in pregnant women. PMID- 1921511 TI - Treatment of spasmodic torticollis. PMID- 1921512 TI - Impact of federalism on the State Legislature. PMID- 1921513 TI - Longitudinal Gompertzian analysis of stomach cancer mortality in the U.S., 1962 1987: a thermodynamic analogy of its declining mortality. AB - Age-adjusted mortality rates for stomach cancer (SC) in the United States from 1962 to 1987 were subjected to longitudinal Gompertzian analysis. Age-adjusted SC mortality rate distributions between age 50 and 85 years were highly Gompertzian for each and every year for both men and women. The environmental 'temperature' or intensity factor declined (improved) 1.55-fold for men and 2.04-fold for women in 1987 as compared to 1962. If the environmental 'pressure' or frequency factor had remained constant, the age at the theoretical common intersect point would have been 56.0 years for men and 80.0 years for women and overall SC mortality would have increased. However, between 1962 and 1987, non-age-standardized annual crude SC mortality rates decreased 46.8% for men and 44.0% for women. The thermodynamic analogy for this apparent discrepancy is that the environmental 'pressure' factor has not remained constant, but rather declined 51.7% for men and 60.9% for women between 1962 and 1987. This suggests that the overall frequency of environmental challenges that contribute to SC mortality has become significantly reduced. PMID- 1921514 TI - Age-related changes in rates of protein synthesis and degradation in rat tissues. AB - It has been hypothesised that a diminished capacity for protein synthesis and degradation underlies a decreased adaptability to environmental stimuli seen during ageing. In this study rates of total protein synthesis and degradation were examined in rats between 1 and 24 months of age. Synthesis rates in heart, lung, skeletal muscle and skin were based on the uptake of [14C]proline into protein when administered with a flooding dose of unlabelled proline. Degradation rates were derived from the difference between protein deposition and synthesis rates. Total protein synthesis rates in 1-month-old animals ranged from 20.4 +/- 1.3% per day (S.E.M.) in skeletal muscle to 39.6 +/- 1.3% per day in lung. In heart, lung and skeletal muscle, synthesis rates decreased 2-fold during the first 6 months of life, while over the same period in skin they decreased 6-fold. Degradation accounted for the bulk of protein synthesised at all ages, and the age-related changes for rates for breakdown closely mirrored those for synthesis. These results, do not support the hypothesis that a general decrease in protein turnover underlies a diminished adaptability in older animals. PMID- 1921515 TI - Effect of aging on the buffering capacity of fast-twitch skeletal muscle. AB - The effects of aging on the in situ buffering capacity of fast-twitch muscle fibers was examined in the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of specific pathogen free Fischer 344 rats. Muscles were electrically stimulated with trains of impulses lasting 100 ms at a frequency of 80 Hz. Trains were delivered at a rate of 1 Hz for 1 min with the hindlimb circulation occluded. Muscle hydrogen ion (H+) release during stimulation was estimated from the accumulation of metabolites. The free [H+] was measured using an homogenate technique. Muscle buffering capacity (Slykes) was estimated as delta mmol H+/l muscle water/delta pH unit. Muscle pH was unaffected by age both at rest and following stimulation in the TA and EDL. H+ release and buffering capacity were significantly reduced in aged TA muscle but unaffected by age in the EDL. Reduced buffering through metabolic processes accounted for only a small portion of the lower buffering capacity in aged TA. Most of the decrease in buffering capacity appeared to be due to reduced protein buffering. Therefore, aged TA muscle was less able to buffer a given H+ load when compared to adult controls. A more rapid accumulation of H+ during intense stimulation may lead to a earlier onset of fatigue in the aged muscle. It is not clear why the EDL buffering capacity was unaffected by age when the fiber mass profiles of the EDL and TA muscles appear similar (approximately 80% fast glycolytic fibers). It is possible that alterations in activity patterns with aging could have differential effects on the two muscles. Detailed activity pattern and fiber mass analyses are required in adult and aged EDL and TA muscles of Fischer 344 rats to answer this question. PMID- 1921516 TI - Age-related studies of SIg, Leu-4 and concanavalin A receptor densities and capping in human lymphocytes. AB - We compared the cell surface antigen density and capping of three antigens in lymphocytes obtained from healthy, young (mean age 27 years) and elderly (mean age 76), population. There were no differences in the expression of surface immunoglobulin (SIg), concanavalin A (con A) receptors and Leu-4 antigen between the two groups. Kinetic analysis of these molecules revealed a slight decrease in capping in the older population, but the differences were not statistically significant. In order to test the possibility that subjecting the cells to metabolic stress might bring out the differences, we performed a kinetic analysis of SIg and con A capping in the presence of various concentrations of the metabolic inhibitor sodium azide. Although the capping in cells from elderly subjects was slightly more sensitive to azide, no statistical difference was found. Analysis of con A capping by a flow cytometric method yielded similar results, confirming the data obtained by visual capping experiments. We conclude that although a trend toward decreased capping was observed, there is little alteration in the surface molecule capping phenomenon in the age-groups studied. PMID- 1921517 TI - Age-related alteration of brain gangliosides in senescence-accelerated mouse (SAM)-P/8. AB - The senescence-accelerated mouse (SAM)-P/8 was examined with respect to changes in the content and composition of brain gangliosides during aging from juvenile to senescence. The gangliosides were compared with those of control mice, senescence-accelerated resistant mouse (SAM)-R/1. The ganglioside contents in the whole brains of SAM-P/8 and -R/1 were at almost constant level from 0.5 to 6 months, but decreased thereafter until senescence to about 80% of the levels reached at the younger ages. Upon aging, the ganglioside compositions changed with an increase of GM1, and decreases of GD1a, GD1b and GT1b in both strains (GT1b greater than GD1a greater than GD1b). A minor component, GM3 was two to four fold higher in the molecular distributions of the whole brain gangliosides of SAM-P/8 than those of -R/1 at any age examined throughout the life span. The regional gangliosides in olfactory bulb, cerebral cortex, hippocampus, hypothalamus, cerebellum, corpora quadrigemina region, brain stem and medulla oblongata were compared between the two strains at the age of three months. The ganglioside contents in the brain stem and medulla oblongata were lower in SAM P/8 than -R/1, but there was no significant difference between the two strains in the other regions. As a minor component, GM3 was found to occur in a higher concentration in SAM-P/8 than -R/1 in all brain regions examined, except in the olfactory bulb where GM3 was detected as a major component with no difference in the distribution level between the two strains. PMID- 1921518 TI - Implication of lysine residues in the loss of 6-phosphogluconate dehydrogenase activity in aging human erythrocytes. AB - The activity of 6-phosphogluconate dehydrogenase (6-PGDH) decreases in aged human erythrocyte populations. The aged enzyme has 11 lysine residues less than the young enzyme, when they are measured with 2,4,6-trinitro-benzenesulfonic acid (TNBS). Treatment of young enzyme with ascorbate for 15 min produces the loss of 8 lysine residues and the diminution of enzymatic activity. These results suggest that there is a modification of lysine residue in human erythrocytes during senescence, probably caused by oxidation. This modification of lysine residue could imply the loss of enzymatic activity. This result is similar to that found in rat liver 6-PGDH during aging, described previously (Gordillo et al., J. Biol. Chem. 264 (1989) 17014-17019). PMID- 1921519 TI - Normal transitions in synthesis of replacement histones H2A.Z and H3.3 during differentiation of dystrophic myotube cells. A brief note. AB - We previously reported that differentiating G0 myotube cells cultured from normal chicken embryos exhibit a histone synthesis pattern that is highlighted by transitions in the expression of the minor replacement variants H3.3 and perhaps H2A.Z (Wunsch and Lough, Dev. Biol. 119 (1987) 94-99). Because these proteins may be synthesized to maintain chromatin structure during the differentiation and maturation of the skeletal muscle fiber, it was of interest to determine whether they are made at normal levels during the differentiation of dystrophic muscle. To this end, the synthesis of histone proteins in cultured myoblasts and myotubes from normal and dystrophic avian embryos has been characterized by two dimensional polyacrylamide gel electrophoresis and fluorography. Proliferating myoblasts (day 1) as well as two stages of differentiating myotubes (days 3, 4) exhibited histone synthesis patterns that were indistinguishable when comparing normal and dystrophic cells. It is noteworthy that this study also revealed that, in both cell types, the change in H2A.Z synthesis during the myoblast/myotube transition was remarkable, increasing from approximately 20% of the non ubiquitinated H2As in myoblasts to 80% in myotubes. Also, gel staining patterns and immunoblotting detected no differences in the degree of histone ubiquitination between normal and dystrophic cells. These findings indicate that, up to this point in dystrophic differentiation, neither the synthesis nor ubiquitination of histones are perturbed. PMID- 1921520 TI - The urban health care clinic and its substance abuse population. AB - The effect of large numbers of patients with a history of substance abuse upon a health care system is rarely considered, nor is the health care system's response to such a clientele ever assessed. In this preliminary study, the collective effect of large numbers of substance abuse patients upon a clinic serving the urban poor and homeless is evaluated. The study examines the types of problems patients present to the clinic and the health care response, in terms of diagnoses and treatment plans, provided by the clinic. Using a random sample of 163 medical records, a retrospective analysis of reasons for visit, diagnoses and treatment plans was performed. Results indicated that patients with a history of substance abuse were more likely to present with chronic complaints and were not frequent return visitors to the clinic. No significant differences in either diagnoses or treatment plans for patients with a history of substance abuse were discovered. The implication of these results for health services provided to urban poor and homeless patients with histories of substance abuse was considered, as were reasons for the type of system response indicated by the results obtained. PMID- 1921521 TI - Physician referrals and the medical market place. AB - Factors determining the extent to which physicians obtain new patients through referrals are examined. A more thorough understanding of physician referral patterns can help to explain how competitive forces function in this market and how physician characteristics and credentials affect individual performance. Referral networks promote entry by young physicians into both primary and nonprimary care medical markets. Nevertheless, there are marked differences in referral patterns between primary care and nonprimary care providers. For instance, referrals are directly related to the degree of market competition and board-certification status among primary care physicians but not among nonprimary care specialists. Membership in a group practice is related to significantly more referral activity among nonprimary care physicians but not among primary care providers. No significant differences were found in referral patterns by physician sex. Although foreign medical graduates (FMGs) receive proportionately fewer referrals than do U.S. medical graduates, the differences are not large. While earlier research suggests that the returns to board certification are higher for female physicians, the present study finds little evidence that board certification is particularly helpful to either female physicians or to FMGs in terms of obtaining patients on referral. PMID- 1921522 TI - The relationship of hospital characteristics and the results of peer review in six large states. AB - To determine which characteristics of hospitals may be related to a higher quality of care, the association of hospital characteristics with the outcomes of medical record review by state Peer Review Organizations (PROs) was studied. The two data sources were: 1) the AHA 1986 Annual Survey of Hospitals and 2) reviews completed between July 1987 through June 1988 from six large PROs. For each hospital the percentage of cases that failed physician review (the confirmed problem rate) was computed. Hospital characteristics evaluated included financial status, ownership, medical training, technological sophistication, and size. The following characteristics were significantly associated with a lower confirmed problem rate: a higher occupancy rate, greater payroll expenses per bed, a higher proportion of physicians who were board-certified specialists, greater technological sophistication, a higher number of beds, a higher proportion of nurses who were registered, and membership in the Council of Teaching Hospitals. Public hospitals had higher problems rates than private not-for-profit hospitals. All characteristics significantly related to higher confirmed problem rates were also related to higher adjusted mortality rates in a previous study of 3,100 U.S. hospitals. The results suggest that hospital resources, including financial status, training of medical personnel, and availability of sophisticated equipment, are related to the quality of care provided by the hospital. PMID- 1921523 TI - Behavioral interventions to increase adherence in colorectal cancer screening. AB - This investigation was a randomized controlled trial to determine the impact of health education interventions on the return of mailed fecal occult blood (FOB) tests (FOBT adherence) in a colorectal cancer screening program. The study sample included 2,201 men and women aged 50 to 74 years who were members of an Independent Practice Association (IPA)-type health maintenance organization (HMO). Subjects were randomly assigned to a "usual care" Control Group (advance letter, screening kit, reminder letter), and Treatment Groups 1 (usual care + reminder call), 2 (usual care + self-held screening booklet + reminder call), or 3 (usual care + self-held screening booklet + instruction call + reminder call). Bivariate analysis revealed significant differences in adherence (P less than .001) across study groups: Control Group (27%), Group 1 (37%), Group 2 (37%), Group 3 (48%). In addition, a significant positive association between age and adherence (P less than .001) was found. Logistic regression analysis revealed an interaction between sex and treatment. Adherence among men in all treatment groups increased significantly (P less than .0001) in relation to Control Group males. Men in Group 3 also were more likely to adhere than those in Group 2 (P less than .01) or Group 1 (P less than .01). Among women, adherence was significantly higher in Group 3 than in Group 2 (P less than .03), Group 1 (P less than .025), or the Control Group (P = .0008). The primary reason cited for nonadherence was perceived inconvenience of the FOB testing procedure. PMID- 1921524 TI - HIV in Maryland. Experiences and attitudes of family physicians. PMID- 1921525 TI - Successful replacement of traditional psychiatric records with a multi-user computer system. PMID- 1921526 TI - Effects of number of rating scale points upon utilities in a quality of well being scale. PMID- 1921527 TI - Health-related quality of life among patients undergoing percutaneous transluminal coronary angioplasty. AB - A randomized clinical trial was recently conducted to investigate whether a new antiplatelet agent could prevent restenosis in patients who had undergone percutaneous transluminal coronary artery angioplasty (PTCA). Approximately 1,200 patients were enrolled at 13 separate clinical sites. To assess the impact of this intervention on health-related quality of life, a patient questionnaire for telephone administration was developed. This questionnaire focused attention on several specific dimensions likely to be important in this patient population: physical well-being, perceived health, emotional well-being, home management, work, recreation, and social and sexual functioning. This paper describes the instrument that was used in this trial and reports on its psychometric [corrected] properties based on completed interviews with approximately 500 patients at study entry and 1 month after PTCA. PMID- 1921528 TI - Cost-effectiveness and obstetric services. AB - This study employs two risk-adjustment strategies to model the cost-effectiveness of obstetric services for eight hospitals in an urban health maintenance organization. Costs are adjusted by an index based on the expected length of a mother's stay, derived from a two stage regression analysis. Logistic regression of the probability of a cesarean-section on a set of clinical indicators constitutes the first stage. The second stage, an ordinary least squares regression, accounts for 30% of the variation in the logarithm of hours of stay but generates unbiased estimates for various subsets of cases. Adjusted costs per delivery range from roughly 22% below to 31% above the mean. Perinatal mortality rates--adjusted for differences in birthweight, sex, plurality, and race--serve as the outcome indicators. Risk-adjusted costs and risk-adjusted mortality rates are positively correlated with one another (r = .69, P = .06); in particular, the lowest cost hospital generated excellent outcomes. Adjusted cesarean-section rates, however, are not correlated with either adjusted costs (r = -.03, P = .95) or adjusted perinatal mortality rates (r = -.13, P = .75). These results suggest that cost management should focus on staff levels and mix more than on practice patterns and that care management should focus on practice patterns in relation to their influences on outcomes. PMID- 1921529 TI - Hospital outpatient services and Medicaid patients' access to care. AB - This article examines the relationship between the use of hospital outpatient services by Medicaid patients, Medicaid physician fees, and the use of office based physician services. Past research has indicated that the use of outpatient facilities by Medicaid patients substitutes for care by private physicians and might be reduced by raising physician fees, but these studies may be estimated at too high a level of geographic aggregation and include many outpatient services that are not substitutes for office-based physician care. The results in this study, which are estimated using LISREL on county level Medicaid claims data from the state of Illinois, provide little evidence that outpatient care substitutes for care by physicians or that raising physician fees would reduce inappropriate outpatient usage by medicaid patients. PMID- 1921530 TI - Practice mobility among young physicians. AB - This study examines practice mobility among young physicians, based on a large nationwide 1987 survey of physicians under age 40 years and in their second through fifth years of practice. Averaged across all physicians, there is a 10% to 12% chance of changing practices for each of the first 3 years, and about one in three physicians changes within the first 5 years. While the most common transition is from employee to self-employed practices, many practice changes are within employment type. Those starting in a self-employed solo practice are least likely to change practices, while those starting as HMO employees are most likely to change. Multinomial analysis of practice change choices reveals some specialty specific differences in these choices, as well as the effects of experience, schooling, race, sex, debt, family constraints, and locational preferences. High debt is a factor in practice changes, but neither competition nor discrimination against minorities appear to play significant roles. PMID- 1921531 TI - Characterization of geriatric drug-related hospital readmissions. AB - Although some factors placing geriatric patients at risk for hospitalization have been identified, little is known about drug-related problems that contribute to admissions. This study describes a protocol for characterizing drug-related problems that are associated with hospital readmissions. The protocol achieves significant improvements over other studies because geriatric readmissions to a community hospital are classified and the type of drug-related problem and relative contribution of the problem to the readmission are assessed. Thirty-five percent of study patients (n = 706) were readmitted within 6 months of their former discharge and 45 of the readmissions were drug-related. The assessments of three reviewers working independently agreed for 82% of the readmissions (kappa = 0.64). Eighteen percent of the cases identified as drug-related using the protocol were also classified as drug-related according to the hospital ICD-9 coding procedure. One percent of the readmissions classified according to the protocol as not drug-related received ICD-9 codes indicating drug-related problems. These findings suggest that the protocol identified drug-related hospital readmissions with good reliability and sensitivity. The most frequently identified drug-related problems were unexpected adverse drug reactions (n = 10), patient noncompliance (10), overdose (8), lack of a necessary drug therapy (6) and underdose (5). Drug-related factors were a major reason, rather than a contributory reason, for readmission in half of the cases. The study identifies specific drug-related problems that could become targets for preventive interventions. The majority (76%) of the problems identified were potentially preventable and the types of problems found indicate that interventions should be focused on both physicians and patients. PMID- 1921532 TI - Assessment of the impact of coexistent psychologic and medical problems on the Sickness Impact Profile (SIP) measurement of functional status. PMID- 1921533 TI - The measurement of mortality. A risk-adjusted variable time window approach. AB - This paper describes the development of risk-adjusted mortality indices (RAMI) using 1985 MEDPAR data from 657 hospitals. The RAMI methodology is adopted from the Commission on Professional and Hospital Activities, however, both inhospital and post-discharge deaths are counted within time windows that vary by clinical condition. Five different RAMI measures (expected deaths/observed deaths) are developed, compared, and aggregated into various hospital characteristic strata. These measures vary by which discharge is held responsible for deaths within a time window, and whether or not inhospital deaths that occur beyond the time window are included. The RAMIs using varying time windows are compared with the RAMIs based upon inhospital deaths only. The inhospital RAMI was higher for the nonteaching hospitals (.95) as compared with the major and minor teaching institutions (.91 and .89). The RAMIs using the varying time windows, on the other hand, tend to be higher for the teaching institutions (e.g., 1.07 for major teaching hospitals; 0.99 for nonteaching hospitals). PMID- 1921534 TI - Multitrait-multimethod analysis of health-related quality-of-life measures. AB - Interest in health-related quality of life (HRQOL) is burgeoning and there has been a proliferation of self-report measures of HRQOL. However, only two instruments available for measuring HRQOL have been calibrated using empirically derived preferences; both are long and complex. This study tested a brief survey designed to concurrently assess HRQOL and preferences for different HRQOL states. Multitrait-multimethod (MTMM) analysis was used to evaluate the construct validity of the survey in a convenience sample of 116 persons. Two methods were used to assess six aspects of HRQOL: general health perceptions, meaningful activities, outlook on life, physical suffering, self-care activities, and social relationships. HRQOL preferences were assessed using two methods similar to those used for self-reports, as well as one additional method. The construct validity of self-reported HRQOL was supported. On the other hand, substantial method variance and little valid trait variance was observed for the HRQOL preferences. Results are discussed in terms of their implications for evaluating and measuring HRQOL and related preferences. PMID- 1921536 TI - Developing criteria for ordering common ancillary services. AB - This article describes the process utilized to develop criteria for appropriately ordering five ancillary services frequently performed in hospitals: 1) arterial blood gases, 2) electrocardiograms (ECGs), 3) serum electrolytes, 4) chest x rays, and 5) complete blood counts (CBCs). The development of each set of criteria involved an initial consultant, a panel of six additional regional expert consultants, and three national reviewers. Each criteria set was developed through a process involving seven steps: 1) an initial working draft, 2) revisions at an initial meeting of the regional experts, 3) revisions at a second meeting of the regional experts, 4) written comments from the regional experts, 5) written comments from national reviewers, 6) additional written comments from regional experts, and 7) application of the criteria to cases in a community hospital. The change in item content was measured between steps and agreement with individual items was measured at steps 2, 3, and 4. The results indicate that appreciable change in content occurred with each step except step 4. Agreement started fairly high and was over 90% by step 4. The discussion considers the utility of each developmental step, factors affecting the utility of the criteria, the extent to which the results can be generalized, and the need for more research to identify optimal processes for the development of criteria to evaluate quality of care. PMID- 1921537 TI - The effects of hearing impairment on health services utilization. AB - The objective of this study was to examine the effects of hearing impairment on the utilization of physician and hospital services in the U.S. adult population. Andersen's behavioral model of health services utilization served as the conceptual framework for the study, and data used for the analyses were taken from two years (1971, 1977) of the Health Interview Survey. Hearing impaired persons used significantly more physician services than hearing persons. Hearing impairment had no effect on the number of hospitals days used but had a significant, positive effect on hospital contact and hospital episodes. In addition, neither the type nor the severity of the impairment had a consistent effect on utilization. These findings were consistent for both years of study data. The study's findings, implications, and suggestions for future research are discussed. PMID- 1921538 TI - A comparison of cost-sharing versus free care in children: effects on the demand for office-based medical care. AB - Using data from the community based RAND Health Insurance Experiment, the effect of cost-sharing versus free care on the use of office-based medical care in children was examined. Children from families on cost-sharing plans had a 22 percent lower probability (P less than 0.005) of having an episode of care during the study year. Both the number of episodes of care and total charges for outpatient professional services were 30 percent lower (P less than 0.005) with cost-sharing. cost-sharing reduced average charges for medical services by 30 percent (P less than 0.01) and pathology charges by 45 percent (P less than 0.005). cost-sharing reduced medical services received by 26 percent (P less than 0.05) and pathology services received by 43 percent (P less than 0.05) but did not have a significant effect on either the price for medical services or pathology services. It was concluded that there is a large difference between cost-sharing insurance plans and free care in the demand for office-based medical care in children. Cost-sharing results in children receiving fewer services, not lower priced services. PMID- 1921535 TI - Dying of cancer. The place of death and family circumstances. AB - Malignant neoplasms confer a special significance to the relationship between terminally ill patients and their immediate environment and directly influence the patient's place of death. This study analyzed the factors that influenced the place of death of cancer patients in Majorca (Balearic Islands, Spain). A survey was carried out among 335 surviving relatives who acted as primary care-givers. Information from interviews and data from medical records showed that 46% of the deaths occurred at home. The patients' place of residence (two of three patients from rural areas died at home and two of three patients from urban areas died in the hospital) and their sociocultural level (a higher proportion of deaths occurred in the hospital among patients of lower socioeconomic levels) were the family and social factors that had the greatest influence in determining the place of death. The opinions of those interviewed, the majority of whom were women (female/male ratio, 3.5:1), as to the admission and discharge of the deceased from the hospital and the impact on the family of the patient's death were analyzed. There were marked differences in the overall perception of the terminal phase of illness in hospital-centered and home-centered groups. The relatives of those who died at home were significantly less distressed. PMID- 1921539 TI - The impact of economic considerations on clinical decisionmaking: the case of thrombolytic therapy. AB - This study examines the intravenous use of two thrombolytic agents [streptokinase (SK) and tissue plasminogen activator (tPA)] in the acute phase of myocardial infarction (MI). These two agents have very different costs and offer an excellent opportunity to study both the impact of economic factors on clinical decisionmaking and the potential for cost savings by limiting the use of expensive new therapeutic agents. A nationwide survey of the 5,792 acute care general hospitals listed in the American Hospital Association's 1988 data file was responded to by 2,651 hospitals (46%) and revealed that 2,384 of these responding hospitals (90%) were using thrombolytic therapy. For 2,200 of these 2,384 hospitals (92%), the respondent was a physician who primarily used one of the two drugs. Eight hundred eighty-six of these 2,200 physicians (40%) primarily used SK while 1,314 (60%) primarily used tPA. SK users were more concentrated in federal public hospitals (69% used SK) than in nonfederal public hospitals (47% used SK), and were least concentrated in private hospitals (36% used SK). There was no difference between the rate of SK vs tPA use in investor-owned and not-for profit private hospitals. SK users most often (62%) cited various economic factors as the reason for their choice. The users of tPA primarily (73%) cited clinical preferability as the reason for their choice even though trials are still ongoing to see which drug is preferable. Several multivariate analyses shed light upon the association between choice of thrombolytic agent and various additional physician and hospital characteristics. These data clearly indicate that while new therapies are rapidly implemented by the medical community, considerations of cost have a substantial impact upon the pattern of implementation and reflect a desire to implement cost savings in the use of new drugs. PMID- 1921540 TI - Mental health and selection of preferred providers. Experience in three employee groups. AB - While Preferred Provider Organizations (PPOs) are designed to contain the costs of health care, they may not be able to do so if sicker individuals opt not to use PPO providers. This study examined how level of mental health status and prior use of mental health services affected the decision to use or not use PPO providers for mental health care for employees enrolled in fee-for-service plans with a PPO option. Data were obtained from an employee survey and claims data on three large employee groups. It was not possible to examine effects of sickliness on the intent to select PPO providers for mental health care directly because about one half of employees could not identify who they would visit for mental health care or even how they would select a provider for such care. The intent to use PPO or non-PPO providers for general medical care, however, was not significantly associated with mental health status when other factors were controlled. Furthermore, among persons who used mental health services after implementation of the PPO option, those who had previously visited providers who were to become part of the PPO panel tended to stay with PPO providers, while those who previously visited providers who were not to enter the PPO panel subsequently selected away from PPO providers for mental health care. This pattern of results suggests that established individual patient-provider relationships, rather than sickliness, determined the selection of PPO versus non PPO providers for mental health care for employees enrolled in these optional PPO fee-for-service plans. PMID- 1921542 TI - Female veterans' and nonveterans' use of health care services. PMID- 1921541 TI - AIDS-related educational preparation and needs of United States and foreign medical school graduates providing primary care in Los Angeles. PMID- 1921543 TI - [Quitting the tobacco habit in Spain]. AB - BACKGROUND: The tendencies in the cessation from smoking and their determinants provide useful information to developed preventive policies and to predict the evolution of diseases associated with cigarette consumption. Spain is one of the European countries with more prevalent smoking habits in the general population, and thus the study of factors determining cessation from smoking is particularly relevant. METHODS: The socioeconomic, demographic and health-related variables associated with the cessation from smoking were evaluated using the data bank from the National Health Survey carried out by the Ministerio de Sanidad y Consumo in 1987, which includes interviews to 29,647 individuals above 16 years of age. The data were analyzed by the calculation of the quit ratio standardized for age. RESULTS: The quit ratio is influenced by age and sex; it is higher among women and it increases with age. The results are questionable regarding the relation with educational level, family income and occupation. The smokers of less than 10 or more than 25 cigarettes/day are those with a higher quit ratio. The quit ratio is also higher in individuals with health problems, a higher rate of use of health services and in those without usual alcohol consumption. CONCLUSIONS: The profile of the individuals who quit smoking in Spain has specific features when compared with other countries, particularly regarding the higher quit rate among women and the lack of a linear correlation with indicators of socioeconomic level. PMID- 1921544 TI - [Intrafamilial contagion with the hepatitis B virus]. AB - BACKGROUND: A study of the intrafamilial transmission of the hepatitis B virus (HBV) and its relationship with the viral replication and epidemiological factors. METHODS: The intrafamilial transmission of 106 chronic carriers of HBV was evaluated: 79 were asymptomatic carriers (AC) and 27 had chronic liver disease (CLD). Overall 347 relatives of the first group individuals and 112 of the second group were investigated. In the index cases, all HBV markers were investigated, and also DNA-HBV in those with CLD. In the relatives, HBsAg, HBsAc and HBcAc were investigated. Also, a survey to evaluate the influence of socioeconomic and cultural factors was also carried out. RESULTS: The prevalence of markers was significantly higher in the relatives of patients with CLD (HBcAg, HBcAc and evidence of contact) followed by AC and controls. The most infective relation in AC was that of other contacts with significant differences from the mother-child relationship (HBsAc p less than 0.003, HBcAc p less than 0.01, and evidence of contact p less than 0.001). By contrast, in CLD the most infective relation was mother-child. The mother-child relation was more infective than the father-child one (HBsAg p less than 0.05, HBcAc p less than 0.03, and evidence of contact p less than 0.02). Regarding viral replication, it was found that the HBeAg and DNA positive patients were more infective. The prevalence of HBcAc and the evidence of contact increased with the time of living together of spouses. Finally, it can be stated in a general sense that, according to the results of the survey, the socioeconomic factors have a small influence on the familial transmission. CONCLUSIONS: The relatives of HBV carriers, particularly in the case of HC with high replication, have a high risk of transmission. Thus, their investigation and subsequent vaccination is mandatory. PMID- 1921545 TI - [Chronic prostatitis]. PMID- 1921546 TI - [Zidovudine and human immunodeficiency virus infection: when and how to initiate treatment]. PMID- 1921547 TI - [Uniformity required for manuscripts submitted to biomedical journals. The International Committee of Medical Journal Editors]. PMID- 1921548 TI - [The treatment of cystitis due to cytostatics]. PMID- 1921549 TI - [The postnatal development of obesity and other changes in the control of body weight]. PMID- 1921550 TI - [A biopsychosocial model in cancer patients]. PMID- 1921551 TI - [Cardiac tamponade as the initial manifestation of a neoplasm]. PMID- 1921553 TI - [The eclipse of medical authors]. PMID- 1921552 TI - [Autoantibodies and Leishmania infection]. PMID- 1921554 TI - [Somnolence during diosmin treatment]. PMID- 1921555 TI - [Primary pulmonary hypertension, anticardiolipin antibodies and human immunodeficiency virus infection]. PMID- 1921556 TI - The role of expert system shell induction in the analysis of phase and amplitude images obtained from nuclear cardiology. AB - In an attempt to explain the results of a perception experiment, estimates of statistical parameters were obtained from phase and amplitude images of nuclear medicine multiple-gated cardiac studies. A commercially available induction system was used to create a rule-based decision tree using these estimates as a training set. In the classification of normal and abnormal studies two useful rules were found; one of these involved the standard deviation of the left ventricular phase histogram and the other concerned the correlation of adjacent pixels in the left ventricular region of the amplitude image. A discriminant analysis performed on five amplitude and five phase parameters produced no better discrimination than the use of the phase standard deviation alone. Although it was hoped that induction would find more than two useful rules, the results of the discriminant analysis confirm that induction has performed creditably on a difficult problem. PMID- 1921557 TI - Computer-assisted analysis of the echocardiogram in the clinical environment. AB - Ultrasound imaging of the heart can provide an important source of diagnostic data to the cardiologist, but conventional echocardiography requires considerable expertise, and is extremely time-consuming. Computer-based analysis is therefore very attractive and, in the light of decreasing hardware costs in recent years, has become increasingly viable in practice. This paper describes the specification and implementation of a computer-based tool which supports the clinician in the analysis of echocardiograms, exploiting the clinical judgement and inherent skill of the clinician. The design of the system has focused particularly on the provision of a powerful user interface for ease of interaction, flexibility in system functionality, and extensive interactive capabilities to maximize reliability and convenience of use. This paper will describe the principal features of the system and illustrate its use in the clinical environment. PMID- 1921558 TI - Data representation for subsequent image interpretation. AB - Radiological scans acquired using either the X-ray CT or the NMR imaging techniques provide a wealth of information about tissue behaviour under that imaging modality and contrast agent. To reason about the image in an interpretation stage the scans have to be converted from a pixel by pixel representation to a symbolic form. The technique used by us to generate such a description is region-based segmentation. Each region refers to a pixel or group of pixels having a common attribute. This work has provided a quantitative measure for the partial evaluation of the segmentation which can be applied independent of attribute or combination of attributes. From our initial studies of the behaviour of CT scans a precept for segmentation was developed. The segmentation employs a one-to-one map as an adaptive mechanism. The segmentation criterion at each point in the image therefore depends on the value at the corresponding point in the map. Any process can be used to generate this map, and so easily utilizes new operators as they are developed. PMID- 1921559 TI - A blackboard architecture for automating cephalometric analysis. AB - This paper describes a principled attempt to use artificial intelligence methodologies for interpretation of lateral skull X-ray images. Lateral skull X ray images are routinely used in cephalometric analysis to provide quantitative measurements useful to clinical orthodontists. Manual and interactive methods of analysis are known to be error-prone, and time-consuming. Previous attempts have been made to automate this analysis, using conventional algorithmic approaches. Unfortunately such systems typically fail to capture the expertise and adaptability required to cope with the variability in biological structure and X ray image quality found in cephalograms. The present system makes use of a blackboard architecture and multiple knowledge sources within an integrated model based system. A data-gathering system allows models of feature appearance and location to be built from examples. Blackboard and task control modules allow specific knowledge-based modules to act on information available to the blackboard. Knowledge-based modules include location hypothesis, intelligent segmentation, and constraint propagation systems. Results from a working experimental system are given, and compare favourably with previous algorithmic solutions. PMID- 1921560 TI - Computer-aided interpretation of SPECT images of the brain using an MRI-derived 3D neuro-anatomical atlas. AB - Nuclear medicine images have comparatively poor spatial resolution, making it difficult to relate the functional information which they contain to precise anatomical structures. A 3D neuro-anatomical atlas has been generated from the MRI data set of a normal, healthy volunteer to assist in the interpretation of nuclear medicine scans of the brain. Region growing and edge-detection techniques were used to semi-automatically segment the data set into the major tissue types within the brain. The atlas was then labelled interactively by marking points on each 2D slice. Anatomical structures useful in the interpretation of SPECT images were labelled. Additional, more detailed information corresponding to these structures is provided via an interactive index which allows access to images, diagrams and explanations. Registration of patient SPECT studies with the atlas is accomplished by using the position of the skull vertex and four external fiducial markers attached to the skin surface. The 3D coordinates determined from these points are used to calculate the transformation required to rotate, scale and translate the SPECT data, in 3D, to match the atlas. Corresponding 2D slices from the two 3D data sets are then displayed side-by-side on a computer screen. A cursor linking the two images allows the delineation of regions of interest (ROIs) in the SPECT scan based on anatomical structures identified from the atlas. Conversely regions of abnormal isotope distribution in the SPECT image can be localized by reference to corresponding structures in the atlas. PMID- 1921561 TI - A knowledge-based system paradigm for automatic interpretation of CT scans. AB - The interpretation of X-ray CT scans is a task which relies on specialized medical expertise, comprising anatomical, modality-dependent, non-visual and radiological knowledge. Most medical imaging techniques generate a single scan or sequence of two-dimensional scans. The radiologist's experience is gained by interpreting two-dimensional scans. The more complex three-dimensional anatomical knowledge becomes significant only when non-standard slice orientations are used. Hence, implicit in the radiologist's knowledge is the appearance of anatomical structures in standard two-dimensional planes, transverse, sagittal and coronal. That is, position with respect to both a coordinate reference system and other structures; intensity ranges for tissue types; contrast between structures; and size within the slices. Further to this, neurological landmarking is used to establish points of reference, i.e. more easily identifiable structures are first found and subsequent hypotheses are formed. With this in mind we have developed a knowledge-based system paradigm that partitions an image by applying the domain dependent knowledge necessary (1) to set constraints on region-based segmentation and (2) to make explicit the expectation of the appearance of the anatomy under the imaging modality for use in the region grouping phase. This paradigm affords both expectation- and event-driven segmentation by representing grouping knowledge as production rules. PMID- 1921562 TI - Mapping between MR brain images and a voxel model. AB - This paper describes an approach to establish the correspondence between a magnetic resonance (MR) image of the brain and a slice through a 3D anatomical model. The model is of voxel structure that symbolically labels primary tissue types such as grey matter, white matter, CSF, etc. In this approach a slice is first searched for in the model to achieve the best general match with the brain MR image in question. The operation involves a minimization of parameters such as position, rotation, slant, tilt and enlargement. Having thus found a globally good registration between the image and the model, local matches that link every pixel in the image through to the model slice are then searched for. This pixel by-pixel match is expressed within a pair of maps, one for the vertical deformation and the other for the horizontal one. The matching algorithm consists of a series of octave separated blurring convolutions combined with exhaustive grey-valued correlation. Because every pixel in the model slice is labelled in terms of its tissue type, and because every pixel in the image has been matched directly to the model, every pixel in the image is now classified. This classification is used directly to perform segmentation which serves as a basis for the computation of medically relevant indices. PMID- 1921563 TI - Three-dimensional reconstruction of arteries from biplane angiograms. AB - The automatic production of three-dimensional computer models of arteries is described, where the originating data are a pair of biplane X-ray angiograms. It is shown that a limited number of plausible reconstructions can be built without use of anatomical knowledge, other than the realization that arteries are continuous, connected pipes. There are indications that further research will be able to identify the unique reconstruction that matches the original structure. The process avoids the extensive human operator intervention and simplifying assumptions used by other researchers. PMID- 1921564 TI - Evaluation of a CCD-based facial measurement system. AB - This paper describes the configuration and evaluation of a CCD-based biostereometric system at the Department of Orthodontics, Kings College Dental Hospital, London. The system has been designed to allow rapid and accurate measurement of facial soft-tissue shape with a minimum of traditional photogrammetric training. This has been achieved by automatic camera calibration and stereo matching, performed on a Sun Microsystem 3/160 workstation. In summary, the characteristics of the system are: (a) non-contract three dimensional (3D) measurement of soft-tissue; (b) de-skilled, requiring little or no photogrammetric training; (c) rapid data acquisition, combined with slower off line processing; (d) processing of resulting 3D surface information to yield cross-sections; (e) surface measurement accurate to within 0.5 mm. Accuracy assessment was performed using a manual electromechanical non-contact measurement device with precision exceeding the requirement of the biostereometric system. PMID- 1921565 TI - Extraction of quantitative blur measures for circumscribed lesions in mammograms. AB - This study investigates ways of improving lesion diagnosis in mammograms by deriving quantitative descriptions of the lesion periphery. The descriptions are derived by computer image analysis methods. The degree of blur at lesion boundaries is of prime concern, as poorly outlined lesions can indicate malignancy. The need for quantitative analysis arises from psychological evidence suggesting that the human visual system cannot precisely estimate the degree of blur. To help find suitable measures a set of 'artificial' lesions has been generated by convolving a step-like edge with a set of Gaussian functions G(sigma) where sigma characterizes the degree of blur. From these generated lesion images the parameters sigma are derived by the process involving deconvolution. As the edge changes are most important in radial directions, the measures of sigma are calculated for each radial profile of the lesion. The derived individual values correspond very closely to those used to generate the lesions. Statistical measures obtained from them allow distinction between edges which are blurred to different extents and yet are impossible to differentiate visually. The artificial lesions will be combined with mammographic data, and similar measures derived. The work will be validated on real lesions for which the histological findings are known from performed biopsies. PMID- 1921566 TI - A robust and accurate method for calculating the fractal signature of texture in macroradiographs of osteoarthritic knees. AB - In osteoarthritis of the knee, horizontal trabeculae in the tibia thicken, leading to the appearance of horizontal striations on radiographs. Any attempt to understand and monitor the disease process must examine these changes. We have previously described a method of analysing the texture in these images that uses the mathematical morphology operations of dilation and erosion to calculate how image fractal dimension varies with resolution. This variation with resolution is the fractal signature. Calculation of fractal dimension should be independent of linear transformations in image values, and it is shown that careful choice of morphological structuring element is required for this. In this paper we describe the dependence of our method of calculating the fractal signature on image acquisition and digitization parameters. Errors due to variations in pixel size, X-ray exposure, and patient repositioning are small compared to the changes seen in the signature due to osteoarthritic change. Using pairs of orthogonal structuring elements, one tuned to calculate the signature due to horizontal image structure and the other for vertical image structure, texture directionality is examined. The difference between the two resulting signatures in individual knees is shown to be a measure of the change in texture seen in osteoarthritis. PMID- 1921567 TI - Automatic analysis of gated heart studies using a Galois lattice. AB - Gated heart studies are currently assessed using the parametric images of first harmonic phase and amplitude in addition to the original images. More information can be obtained by multi-harmonic analysis, but the quantity of information is too great to be assessed by visual methods alone. We propose an automatic diagnosis support system which will use all the additional information, compress and analyse the data, and present the results in a single image to assist the consultant in his or her diagnosis. Multi-harmonic analysis produces many parameters to describe features of the images. A set of parameters will be selected using guidelines that link parameters and intervals of their values to clinical conditions. Images are processed using these parameters and the results stored in a binary matrix. A Galois lattice structure is then derived from the matrix where a vertex of the lattice represents a 'significant' region of the heart together with a 'logic description' of this region. Using this, areas of clinical interest can be found and displayed on a diastolic image of the heart. PMID- 1921568 TI - Introduction: drug delivery systems and devices. PMID- 1921569 TI - Targeting in the gastrointestinal tract: new approaches. AB - Most drug products are administered via the alimentary canal; prominent are the dosage forms which are swallowed, i.e., p.o. dosage forms, followed by those administered within the oral and the rectal cavities. The innermost surface of the alimentary canal is the epithelial lining which is void of keratinized superficial layers. The epithelium at both ends of the canal, i.e., oral cavity and esophagus, and anal canal is a multilayered (20-50 layers) stratified squamous epithelium, whereas that of the rest of the canal, i.e., gaster, small and large intestine and rectum is a single layer of columnar cells. The drainage is via both venous blood capillaries and lymphatic vessels. Blood drainage from the oral cavity and the lower end of the rectum is directly into systemic circulation via the vena cava. From the GI tract, however, the blood quantitatively passes through the portal vein and liver, hence is available for first-pass effect prior to entering systemic circulation. Targeting can be approached from two angles: 1) to exert the pharmacologic response at a specific site, or 2) to utilize a specific site for drug absorption. Targeting utilizes the anatomic, histologic, physiologic and biochemical features of various segments within the alimentary canal, paired with the design of special drug delivery systems or devices, and the use of special vehicle substances, such as polymers, bioadhesives, sorption promoters, or chemical modification (pro-drug) of the active moiety. Numerous examples of new types of drug delivery systems are presented. Many novel drug delivery systems discussed are still in experimental stage and evaluation, or even in the conceptual stage. However, it is anticipated that they all will contribute to further advancement in optimizing drug therapy. PMID- 1921570 TI - Nanoparticles and liposomes: a state of the art. AB - The loading of drugs into ultrafine host vesicles or colloidal capsules in the nanometer size range is an acknowledged technique for the optimization of controlled drug delivery. The main purpose will always be to design inert auxiliary accompanying materials; to use body-friendly and biodegradable excipients; and to miniaturize the drug carrier system dramatically in order to get good stability, excellent absorption, quantitative tissular transfer and, therefore, the expected pharmacodynamic activity. Furthermore, side effects and foreign body irritation should be avoided and a good local and systemic tolerance during and after medication should be a condition sine qua non. The actual state of the art is shown with 4 practical application examples, namely: a cellular uptake by endocytosis and a specific lysosomotropic cell transfer with cell tracer-loaded nanoparticles; the strong immunosuppressive stimulation of nanocapsules--as new adjuvants--when loaded with viral or other antigens; the better blood-brain barrier transfer of an antiparkinson drug when covalently bound to special liposomes; and the use of minivesicles for controlled site specific anticancer drug release (tumor targeting). In the future, we must find a possibility to deliver the correct dose of the drug precisely to the diseased target organs, tissues or cells of destination, without flooding the organism with massive drug doses. One technologic answer could be the minicarrier concept with specific pathfinders and aspecific pretargeters that serve as switchmen to guide the drug-loaded carrier to the organs, with precise spot landing. PMID- 1921572 TI - Iontophoresis--is there a future for clinical application? AB - Transdermal application of drugs is a field of great importance in medical therapy. The application is painless and may be controlled at any time. Iontophoresis is one method for transdermal application of substances, especially for larger or charged molecules which cannot be administered by a simple transdermal route. The problems arise from the complex equipment and the electrical properties of the skin. A better understanding of skin structure and electric transmission through human skin has led to renewed interest in iontophoresis as an administration mode. Iontophoresis is the method of choice in administration of certain local anesthetics and has had its greatest success in therapy of hyperhidrosis. New applications are to be expected, particularly in administration of peptide and protein drugs. PMID- 1921571 TI - Transdermal therapeutic systems--actual state and future developments. AB - Modern transdermal therapeutic systems have been marketed since the last decade only. Nitroglycerin, scopolamine, clonidine, estradiol and nicotine are the current prominent representatives that have matched expectations regarding therapeutical benefits based on TTS applications. Although different TTS constructions have been realized, it is nevertheless appropriate to consider the governing role of the skin permanent. As the upper skin barrier limits flux rates, drug uptake has to be improved by the TTS's own occlusion or by flux enhancers. Enhancers act either on the hydrophilic keratin matrix or on the lipophilic intercellular material in the stratum corneum. Improvements in drug diffusion must be balanced carefully with the risk of skin irritation. In the future we should expect, among others, pulsatile systems to avoid tolerance, or systems comprising fixed combinations of transdermal drugs within one TTS, possibly at first in the field of hormones. Other expectations will be discussed. Therapeutic benefits are expected by the administration of highly potent topical drugs by means of TTS-analogous therapeutic systems, enabling a time-controlled drug release for purposes of topical treatment only. PMID- 1921573 TI - Pharmacodynamic effects of transdermal bupranolol and timolol in vivo: comparison of microemulsions and matrix patches as vehicle. AB - Transdermal administration of drugs possesses several advantages in therapy, but is limited by generally poor penetration through the skin. The aim of this study was to assess whether in vivo transdermal absorption could be enhanced by using microemulsions (ME) as vehicles. Water uptake from the occluded skin changes the water-free microemulsion base (MEB) into a ME. The increasing content of water decreases the solubility of apolar drugs. This leads to in situ formation of a super-saturated ME that possesses a particularly high absorption rate due to the enhanced diffusion pressure of the drug. A saturated solution of the model drugs bupranolol (B) and timolol (T) in a water-free microemulsion base was applied to an clipped area of the dorsal skin of rabbits with an occlusive patch. Evaluations were made in comparison to matrix patches (M) containing 1.2 mg/cm2 B or 2.0 mg/cm2 T. The beta-blocker dose applied was 2.0 mg/kg body weight throughout the study. The measured parameter of the pharmacodynamic effect was the maximal heart rate (HR) after an i.v. bolus injection of a standard dose of isoproterenol. Observations were made in different intervals over a 10-h time period after application of the patches. The response to isoproterenol was calculated as beta-blocker effect. Faster increasing effects and higher maxima for both drugs was found after application in MEB compared to M. After administration of B and T in MEB the effects were found to be identical, with a maximum (85-90%) after 2 h. Application in M showed B to be less effective (34%, 10h no plateau) than T (74%, 10h). Therefore microemulsions represent an improved vehicle for transdermal administration of test drugs. PMID- 1921574 TI - [The Cancer Foundation and the popular movements]. PMID- 1921575 TI - [Why a person choose to study medicine? Interest in natural sciences and the will to work with people determine the occupational choice]. PMID- 1921576 TI - [Medical revision for quality is the 3rd revolution in health care services]. PMID- 1921577 TI - [Active listening is an important part of the treatment of musculoskeletal disorders]. PMID- 1921578 TI - [Information on vaccination against whooping cough will be released in the autumn]. PMID- 1921579 TI - [Surgical experience can not be reduced by organization]. PMID- 1921580 TI - [Growth factors as a possibility to accelerate the healing of leg ulcers]. PMID- 1921581 TI - [Evaluation of the media campaign Heart-Pain-90,000: time delay in acute myocardial infarct can be reduced]. PMID- 1921583 TI - [Nursing ethics in a multicultural society. Culture-sensitive care demands self knowledge as well as knowledge and respect for other cultures]. PMID- 1921582 TI - [Significant shortages and problems in several fields: quality assurance is both necessary and desirable in future health care services]. PMID- 1921584 TI - [Pulmonary hydatidosis--an unusual cause of recurrent hemoptysis]. PMID- 1921585 TI - [Choriocarcinoma--an unusual tumor with higher incidence among men]. PMID- 1921586 TI - [Amalgam as dental filling. Health insurance authorities allow compensations for mercury poisoning based on weak indications]. PMID- 1921587 TI - [The dentist can help many patients with oral galvanism]. PMID- 1921589 TI - [Scandinavian cooperation for influencing food habits]. PMID- 1921588 TI - [The man behind the clamps. Jules Emile Pean. He boasted with his technique of minimal blood loss during surgery]. PMID- 1921590 TI - [Oncologic training of the personnel--a regional responsibility]. PMID- 1921591 TI - [Occurrence of life-threatening allergic reactions after thrombolysis is not sufficiently explained]. PMID- 1921592 TI - [The role of hospital hygiene is important in the quality assurance of the health care]. PMID- 1921593 TI - [Intensified treatment of insulin-dependent diabetes results in milder complications]. PMID- 1921594 TI - [Intracerebral hemorrhage and serum sickness after thrombolytic treatment in myocardial infarction]. PMID- 1921595 TI - [Progress in spinal surgery makes it possible to help patients with metastases in the vertebral column]. PMID- 1921596 TI - [A study of 10 children. Positive effects of central nervous system stimulants in hyperactivity and attention disorder]. PMID- 1921597 TI - [Irrational factors direct the follow-up of my patients]. PMID- 1921598 TI - [A USA verdict: the patient has no right to removed organs]. PMID- 1921600 TI - [Computer-based epicrisis is the first important step on the way towards surgical quality assurance]. PMID- 1921599 TI - [Acknowledgement of errors is part of the core of quality assurance: "To err is human, mistakes are made even in patient care..."]. PMID- 1921601 TI - [Widening the concepts of ethics and health result in more appropriate steering instruments]. PMID- 1921602 TI - [Hyperammonemia originated from the test tube not from the patient]. PMID- 1921603 TI - [There are still problems in the occupational environment of female physicians]. PMID- 1921604 TI - [The Supreme Court overturned the verdict against physicians in a case on a patient's informed consent]. PMID- 1921605 TI - [Unemployment and ill-health--a challenge for the general practitioner]. PMID- 1921606 TI - [Let Selexid regain its role as a drug of first choice in lower urinary tract infections]. PMID- 1921607 TI - [A warning about risk of errors when prescribing Losec!]. PMID- 1921608 TI - [Both physicians and the patients are unfamiliar with drug packages for rheumatic diseases]. PMID- 1921609 TI - [New discoveries on characteristics and treatment in generalized anxiety syndrome]. PMID- 1921610 TI - [Unemployment among adolescents causes impaired health and increased abuse]. PMID- 1921611 TI - [Complications are significant result-indicators for quality control in surgery and anesthesiology]. PMID- 1921612 TI - [Alcohol detoxification can often be done on ambulatory basis]. PMID- 1921613 TI - [A clear therapeutic strategy is necessary in ambulatory alcohol detoxification]. PMID- 1921614 TI - [Swedish forensic psychiatry 1991--before deciding on its direction]. PMID- 1921615 TI - [A consensus conference in forensic psychiatry is needed to coordinate survey and care]. PMID- 1921616 TI - [Better specified and defined diagnoses are the basis for updated classification of diseases]. PMID- 1921617 TI - [Firm routines are necessary for transportation of foreign patients to their home]. PMID- 1921618 TI - [Drug control. The control function of the authorities is emphasized in several countries]. PMID- 1921619 TI - [Acid-reducing treatment before gastroscopy, yes or no?]. PMID- 1921620 TI - [Extend postoperative single-day care--a future model for otorhinolaryngologic surgery?]. PMID- 1921621 TI - [Is health care and research to be separated? Randomized controlled trials are important]. PMID- 1921622 TI - [A study of psychiatric long term care. Mentally ill elderly persons with behavioral disorders need not only nursing home care but also other forms of care and housing]. PMID- 1921623 TI - [Complement deficiency and meningococcal infections--clinical, course, diagnosis and prevention]. PMID- 1921625 TI - [Experiences with medical audit at a health care center: defined problems with clear criteria have the best chance of successful revision]. PMID- 1921624 TI - [The Norrkoping study. Cephalosporins are often the implicating factors in Clostridium difficile infections]. AB - In a retrospective study carried out at Norrkoping Central Hospital, the incidence of Clostridium difficile-associated diarrhoea and colitis was found to be correlated to in-patient consumption (in terms of defined daily doses) of the implicated anti-microbial agents. The third generation cephalosporin, cefotaxime, was implicated 38 times more often than small spectrum penicillins. In general, the cephalosporins were predominantly responsible, accounting for 46 per cent (67/147) of the episodes but only 12 per cent of overall consumption of antibiotics at the hospital. These findings are in accord with data previously published in the nationwide report by the Medical Product Agency, Uppsala. PMID- 1921626 TI - [Flail chest treated by suspension of the thorax, without respirator]. PMID- 1921627 TI - [Prions and Trypanosoma as a source of knowledge of the brain]. AB - Recent research on prions and trypanosomes is reviewed as they constitute examples of how infectious agents can cause degenerative diseases or functional disturbances in the nervous system. Prions are novel, transmissible pathogens causing degenerative diseases of the central nervous system both in humans and in animals. Kuru, Creutzfeldt-Jakob's disease and Gerstmann-Straussler-Scheinker's (GSS) syndrome illustrate the acquired, sporadic and genetic manifestations of the human prion diseases, respectively. Prions are composed largely, if not entirely, of an abnormal isoform of the prion protein, which is a normal cellular protein occurring at high concentrations in the central nervous system. Specific mutations in the prion gene may cause the sporadic and hereditary human disease. S B Prusiner's group at the University of California has used genetic engineering techniques to recreate GSS syndrome by transplanting the mutated prion gene into mice in which the effects of the prion protein genes can then be studied. Trypanosomes are extracellular parasites which cause distinct functional disturbances of the nervous system, although they do not penetrate the blood brain barrier. Factors are now being isolated in the interactions between the parasites and the immunesystem, and the effects of such factors on the functional properties of neurons are studied. PMID- 1921628 TI - [Medical perspective. Septic shock, infections and multiple organ failure as challenge for intensive care in the 1990's]. PMID- 1921629 TI - Lipomas of the internal auditory canal. AB - Intracranial lipomas are rare tumors which may occur in the cerebellopontine angle (CPA) or internal auditory canal (IAC). Although seemingly innocuous in other parts of the body, lipomas within the CPA and IAC often involve the surrounding cranial nerves, making attempts at hearing conservation largely unsuccessful. In an attempt to differentiate the IAC lipoma from the more commonly found acoustic schwannoma, the preoperative imaging studies (magnetic resonance and computerized tomography) on five previously unreported cases of IAC lipomas were evaluated. Based on these studies, features were determined that may allow the surgeon to diagnose IAC lipomas preoperatively. These features will be discussed, as well as the surgical and pathological findings. PMID- 1921630 TI - Malignant nerve sheath tumors of the head and neck: a combined experience from two university hospitals. AB - Malignant schwannoma is an aggressive neoplasm whose cell of origin and histologic characteristics remain controversial. Despite advances in diagnostic techniques, the natural history of this tumor remains uncertain. The charts of all patients with malignant schwannoma who were treated at the UCLA Center for the Health Sciences and the University of Iowa Hospital and Clinics were retrospectively reviewed. Sixteen patients received surgery and radiotherapy in combination or as sole therapy. Irrespective of treatment modality, prognosis was poor with an overall survival of 15%. Recent advances in imaging and histologic techniques that assist in establishing the diagnosis and delineating tumor location are discussed. In addition, the literature pertaining to malignant schwannoma of the head and neck is reviewed. PMID- 1921631 TI - A histopathological study of the relationship between otitis media and mastoiditis. AB - From a total of 1408 human temporal bones, 229 with otitis media or mastoiditis were selected; other contributing diseases were excluded. Of this group, 19.2% had an obstruction of the aditus ad antrum with pathologic tissue, usually granulation tissue. Although pathologic fluid and tissue were usually distributed throughout the middle ear and mastoid, in some cases, the most severe conditions were restricted to the mastoid. Pathologic conditions were more severe in cases with obstruction. An interesting observation was that columnar epithelial cells, goblet cells, and mucoid effusion were not observed in the mastoid, suggesting a restriction of secretory cells to the middle ear proper. It appears that obstruction of the aditus ad antrum contributes to the pathogenesis and accentuates pathologic conditions in otitis media. PMID- 1921632 TI - Clinical assessment of postural stability following vestibular nerve section. AB - Little is known about the recovery of postural control in patients following acute vestibular loss. This paper reports on the results of moving-platform posturography to assess the recovery of postural stability in 24 patients following vestibular nerve section. Posturography was abnormal prior to surgery in 17% of the patients. Seven days following surgery, 44% of the patients demonstrated vestibular deficit patterns, while 56% of the patients had normal posturography. Posturography was normal in all patients 1 month following surgery. Abnormal posturography was subsequently noted in 21% of the patients between 3 and 20 months following surgery. Each of the patients with abnormal preoperative posturography subsequently demonstrated abnormal late postoperative posturography. These results suggest that perioperative posturography may be useful in the evaluation and counseling of patients considering ablative vestibular surgery. PMID- 1921633 TI - Central nervous system changes associated with noise-induced hearing loss: an electron microscopic and freeze-fracture study of the chick nucleus magnocellularis. AB - This investigation assessed the effects of noise-induced hearing loss on the avian nucleus magnocellularis, the homologue of the mammalian cochlear nucleus. Fifteen-day-old chicks were exposed to high-intensity broad-band noise (132 dBA) for 24 to 72 hours. Hearing loss was documented with auditory brain-stem response recordings and scanning electron microscopy of the basilar papilla. Nucleus magnocellularis was assessed with thin-section electron microscopy and freeze fracture techniques. Freeze-fracture preparations of noise-exposed animals showed a decrease in synaptic vesicle fusion sites at the synaptic active zone, a decrease in re-uptake of presynaptic membrane by coated vesicles, and a shift of the preferential fracture plane at the synapse from the presynaptic membrane to the post-synaptic membrane. These findings support the hypothesis that the effects of noise are not limited to the auditory periphery, but that transneuronal changes extend into the auditory central nervous system. PMID- 1921634 TI - Development of monoclonal antibodies with specificity to oral squamous cell carcinoma. AB - A panel of five monoclonal antibodies have been produced that show binding when directed against human oral head and neck squamous cell carcinomas. These monoclonal antibodies are derived from antibody-secreting cells obtained using cell hybridization techniques. The activity of the antibody was tested in vitro against oral head and neck squamous cell carcinoma (n = 10). Control groups included normal oral mucosa (n = 7), hyperkeratosis (n = 5), mild dysplasia (n = 4), and severe dysplasia (n = 3). Results using immunoperoxidase staining confirmed the binding of the five monoclonal antibodies to human head and neck squamous cell carcinoma cells, with predominant reactivity (50% to 90%) in the majority of the specimens, compared with negative (0%) to weak (less than 5%) or focal (5% to less than 50%) reactivity in the control specimens. PMID- 1921635 TI - Response of the stria vascularis to corticosteroids. AB - Structural changes in the cellular architecture of the stria vascularis in adrenalectomized rats were quantitated by stereological methods after the administration of either aldosterone or dexamethasone. The volume densities of the differing strial components from steroid-administered animals were determined to approximate those of sham-adrenalectomized animals in general. The increased volume density of intercellular space as was observed following adrenalectomy, however, was only restored after the administration of aldosterone. These data correlate a recovery of the cellular architecture of the stria vascularis in adrenalectomized animals with the restoration of endogenous levels of adrenal steroids. These findings provide further information with regard to the effects of varying serum levels of corticosteroids on inner ear morphology. PMID- 1921637 TI - The recurrent laryngeal nerve in relation to the inferior constrictor muscle of the pharynx. AB - The point of penetration of the recurrent laryngeal nerve into the larynx is recognized as the most frequent site of injury to the nerve during surgical procedures of the thyroid gland. The anatomical relationships of 25 right and left recurrent laryngeal nerves in 25 anatomical blocks from formalin-fixed human corpses have been studied. In 34 cases (68%), the recurrent laryngeal nerve penetrated into the larynx below the lower fibers of the inferior constrictor muscle of the pharynx (type 1 of penetration). In the remaining 16 cases (32%), the nerve crossed through those muscle fibers to penetrate into the larynx (type 2 of penetration). The thyroid gland was found to involve the recurrent laryngeal nerve at the penetration point into the larynx in 19 of 50 cases (38%). PMID- 1921636 TI - Effects of persistent perilymph fistula on the inner ear. AB - To study the effects of a persistent perilymph fistula on the cochlea, a small cannula was inserted into the scala tympani of the basal turn of cochlea in guinea pigs. A month later, cochlear morphology and blood flow were studied using either histological evaluation or the microsphere surface preparation technique. Some animals showed no cochlear morphologic changes or no cochlear blood-flow reduction, even if tubal patency was maintained and perilymph leakage lasted for 1 month. This suggests that a prolonged perilymph fistula, per se, causes no permanent cochlear damage. However, in some animals, hair cell damage and cochlear blood-flow disorders were observed. These observations and the causes of hearing loss in clinical cases of perilymph fistula were studied. PMID- 1921638 TI - Inverted papilloma of the nasal cavity: pathological aspects in a follow-up study. AB - The initially removed tumors from 42 patients with inverted papillomas of the nasal cavity and paranasal sinuses were subjected to an extensive histopathological examination in order to define the characteristics associated with multiple recurrences and development of malignancy. Two of the patients subsequently developed squamous cell carcinoma and eight patients had more than one recurrence. No specific histological characteristic was determined to be a predictor of multiple recurrences or development of malignancy. However, three patterns of characteristics emerged from the data which were found to be related to the development of malignancy, multiple recurrences, and benign behaviour. Malignancy was found to be associated with bilateral inverted papilloma, a predominance of mature squamous epithelium, the presence of all three epithelial types (metaplastic squamous, mature squamous, and cylindrical), severe hyperkeratosis, a mitotic index greater than or equal to 2 per high-power field (HPF), absence of inflammatory polyps among the papillomas, an abundance of plasma cells, and an absence of neutrophils. Multiple recurrences (without malignancy) were associated with a mitotic index greater than or equal to 2 per HPF and an absence of inflammatory polyps. Benign behaviour was associated with predominantly mucinous tumors, a mitotic index less than 1 per HPF, a ratio of neoplastic epithelium/connective tissue stroma greater than or equal to 6, and the presence of inflammatory polyps among the papillomas. PMID- 1921639 TI - Site of airway obstruction in patients with obstructive sleep apnea before and after uvulopalatopharyngoplasty. AB - This study describes a simple method, based on a movable catheter technique, for use during routine polysomnography to identify the site of obstruction, and this has been applied to 51 patients with suspected sleep apnea. The obstruction was found to be retropalatal in 30, retrolingual in 7, and could not be determined in 14 patients (12 had no sleep apnea, 1 did not sleep, and 1 had central sleep apnea). Twelve of these patients had uvulopalatopharyngoplasty with preoperative and postoperative polysomnograms to determine the site of obstruction. The preoperative obstruction was retropalatal in nine and retrolingual in three. Postoperatively, four patients (one with retrolingual obstruction and three with retropalatal obstruction) no longer had sleep apnea. In the remaining eight patients, the site of obstruction was unchanged from the preoperative one. Several conclusions result: 1. the movable catheter technique offers a simple way to determine the site of obstruction in patients with significant obstructive sleep apnea, 2. most such patients obstruct in the retropalatal region, and 3. preoperative localization of the site of obstruction to the retropalatal region does not seem to improve the surgical outcome of uvulopalatopharyngoplasty. PMID- 1921640 TI - Early stages of facial nerve regeneration through silicone chambers in the rabbit. AB - The early stages of rabbit peripheral facial nerve regeneration [N = 16], over a 10-mm transectional gap, were analyzed at 1, 3, and 5 weeks of buccal nerve entubation in silicone chambers prefilled with saline. Normal nerve pooled data were obtained in nine nerves. Chronologic morphologic and morphometic light and electron microscopic computer-captured data reveal that the regeneration process can be subdivided into four stages: 1. The establishment of an acellular intergap matrix; 2. the ingrowth of mesodermally derived cells (macrophages, fibroblasts, endothelial cells, etc.) to form an intergap scaffolding; 3. the ingrowth of ectodermally derived cells (neurons, Schwann's cells, etc.) to reconstitute the transected peripheral nerve; and 4. neural maturation by progressive axonal enlargement, myelination, and compartmentalization. The first two stages occur during the first week, the third stage during the third week, and the fourth stage from the fifth week onwards of neural entubation. Morphometic analyses indicate that total neuroregenerates increase in number from 303 +/- 286 to 2693 +/- 1334 (+/- values are standard deviations) and myelination of axons increases from 12% to 48% during the third to fifth week of entubation. The thickness of the myelin (g-ratio) increases from 0.89 +/- .01 to 0.74 +/- .06 (SD) during the same period of time. At the end of the fifth week of entubation, the midchambers contain, on the average, 1279 +/- 980 myelinated axons (30% of normal counts) and 483 (+/- 11.2%) axons cross the chambers to innervate the distal transected neural stump (12.5%). Specific target-organ (quadratus labii superioris muscle) activity can be recaptured with a smaller number (12.5%) of regenerating myelinated axons from the buccal division of the facial nerve during the fifth week of entubation. PMID- 1921641 TI - Absorbable mattress sutures in the management of auricular hematoma. PMID- 1921642 TI - Nasal alar reconstruction using the nasolabial turnover flap. PMID- 1921643 TI - Dilazep-induced vasodilation is mediated through adenosine receptors. AB - Administration of dilazep, an inhibitor of adenosine uptake, significantly reduced systemic arterial blood pressure and increased superior mesenteric arterial conductance without affecting the plasma adenosine levels of femoral arterial or portal venous blood. Administration of a bolus dose of 8 phenyltheophylline (8-PT), an antagonist of adenosine receptors, blocked adenosine-mediated autoregulation of the superior mesenteric artery. After the blockade of adenosine receptors by 8-PT, dilazep did not produce vasodilation. These data suggest that dilazep has a vasodilating effect in vivo that is mediated by adenosine. PMID- 1921644 TI - Calcium-dependent inhibition of renin secretion: TMB-8 is a non-specific antagonist. AB - Intracellular Ca (Cai) is an inhibitory second messenger in renin secretion, and it has been hypothesized that some first messengers--especially angiotensin II [A II] and antidiuretic hormone [ADH], and possibly A1-adenosine receptor antagonists as well--increase Cai and thereby inhibit renin secretion by causing the release or mobilization of Ca from intracellular sites of sequestration. The present experiments were designed to test this hypothesis, by using 3,4,5 trimethoxybenzoic acid 8-(diethylamino)-octyl ester (TMB-8), a putative antagonist of Ca release from intracellular sequestration sites. The rat renal cortical slices preparation was used. Basal renin secretory rate was unaffected by 1 and 10 microM TMB-8, but more than doubled in response to 100 microM TMB-8. Basal renin secretory rate was inhibited by A-II (1 microM), by ADH (200 units/1), by an A1-adenosine receptor agonist (N6-cyclohexyladenosine, or CHA; 0.5 microM), and by an alpha-adrenergic agonist (methoxamine; 10 microM). Only the inhibitory effect of methoxamine was blocked by 1 and 10 microM TMB-8, but these concentrations had no effect on basal secretory rate. At 100 microM, TMB-8 blocked the inhibitory effects of ADH as well as of methoxamine, but failed to block the inhibitory effects of CHA and A-II. However, these observations cannot be taken as evidence that methoxamine and ADH, but not CHA and A-II, inhibit renin secretion by a mechanism involving release of Ca from intracellular sequestration sites, because 100 microM TMB-8 clearly had non-specific effects. Among them, it completely blocked the inhibitory effect of K-depolarization on renin secretion. Collectively, at least three separate actions of TMB-8 must be invoked to explain the present results. Likely candidates are an Na-channel blocking effect and a Ca channel blocking effect in addition to antagonism of the release of Cai. PMID- 1921645 TI - Imipramine-fentanyl antinociception in a rabbit tooth pulp model. AB - Antinociception of imipramine (I) and its effect in combination with fentanyl (F) was evaluated in rabbits using electrically-induced lick chew responses via tooth pulp stimulation as the model of nociception. Acute i.v. injections of I elicited a graded dose response comparable to i.v. morphine (M) with I ED 50 = 4.35 mg/kg (2.31-8.14, 95% CL) and M ED 50 = 1.81 mg/kg (1.11-3.90), with no differences in the slopes between the two curves. The lethal dose of I was 10 mg/kg. An i.v. dose of I twice the ED 50 elicited an antinociceptive effect of more than 50% maximum possible effect (MPE) for 90 minutes with peak effect of 82% MPE occurring at 15 minutes. These effects of I were not reversed by a morphine reversal dose of naloxone (0.1 mg/kg i.v.) but were reversed with a ten fold dose of naloxone. F ED 50 values (mcg/kg) were lowered from 11.35 to 2.70, 0.74 and 0.33 with increasing pretreatment doses of I (1.0, 2.1 and 3.2 mg/kg). These magnitudes of potency increases of F were 4.2, 15.3 and 34.4 fold respectively. A single i.v. ED 50 dose of I extended the time to 50% MPE of an ED 90 dose of F from 26 minutes to 77 minutes; of a 2 X ED 50 dose of F from 17 minutes to 28 minutes. Data points for three different combinations of I and F fell significantly within the synergistic field of an ED 50 isobologram and a polynomial equation described the curve best fitting the data points. F alone (i.v. ED 50 dose) increased the PaCO2 values to 74% above controls and three different combinations with I showed no increases in PaCO2 values above controls. I alone did not significantly cause any change in PaCO2 values from controls. PMID- 1921646 TI - Interleukin-2 enhances the release of endothelin-1 from the rat mesenteric artery. AB - We measured the ET-1 concentration in plasma and in the perfusate of the mesenteric arteries of rats treated with a therapeutic dose of IL-2 for 7 days (100000 U/Kg, iv.). The plasma ET-1 concentration in rats given IL-2 was 14.2 +/- 3.2 pg/ml which was significantly greater than that in the controls (2.5 +/- 0.4 pg/ml, P less than 0.05). The mesenteric arteries also released a significantly greater amount of ET-1 (29.5 +/- 1.6 pg/h) than that in controls (16.8 +/- 2.3 pg/h, P less than 0.01). The arterial blood pressure was significantly lower after IL-2 treatment than the pre-dosing level (P less than 0.05). It is concluded that IL-2 induces ET-1 release from the vascular wall, possibly as a result of reversible endothelial dysfunction caused by IL-2. PMID- 1921647 TI - Toxicological effects of an organophosphorus pesticide (dimethoate) on urinary collagen metabolites in normal and high protein diets fed female albino rats. AB - The effect of an organophosphorus pesticide (dimethoate) on the urinary excretion of hydroxyproline (total, nondialysable, dialysable and free fractions) and hydroxylysylglycosides, glucosylgalactosyl hydroxylysine and galactosehydroxylysine was investigated in two groups of female albino rats fed with normal and high protein diets. In comparison to controls, dimethoate treated animals were found to excrete significantly decreased amounts of urinary hydroxyproline fractions from 7th day onwards. The excretion of total hydroxylysylglycoside in urine parallels the excretion of hydroxyproline. The urinary output of both glu-gal-hyl and gal-hyl was also appreciably lower from dimethoate treated animals. The normal ratio of glu-gal-hyl and gal-hyl found in the urine of dimethoate treated animals was discussed in light of decreased turn over of collagen in both bone and skin. The effect of dimethoate in rats fed with high protein diet was comparatively less than those fed with normal diet. PMID- 1921648 TI - Tetrahydroisoquinoline alkaloids mimic direct but not receptor-mediated inhibitory effects of estrogens and phytoestrogens on testicular endocrine function. Possible significance for Leydig cell insufficiency in alcohol addiction. AB - Possible effects of various tetrahydroisoquinolines (TIQs) on rat testicular endocrine function were tested in vitro in order to prove whether these compounds, some of which have been claimed to accumulate in alcoholics, may be mediators of the development of Leydig cell insufficiency, a well-known side effect of ethanol ingestion. TIQ effects on different levels of regulation of testis function were compared in vitro with estrogen effects, since both classes of compounds have structural similarities. Gonadotropin-stimulated testosterone production by testicular Leydig cells was inhibited by tetrahydropapaveroline and isosalsoline, the IC50 values (30 microM) being comparable to those of estradiol (3 microM), 2-hydroxyestradiol (10 microM), and the phytoestrogens, coumestrol (15 microM) and genistein (7 microM); salsolinol (85 microM) and salsoline (240 microM) were less effective, and salsolidine was ineffective. None of these TIQs interacted significantly with testicular estrogen receptor as analyzed by estradiol displacement. However, tetrahydropapaveroline, isosalsoline and salsolinol competitively inhibited (Ki 130-150 microM) substrate binding to cytochrome P450XVII, one key enzyme of androgen biosynthesis, with similar efficiency as the estrogens did (Ki 50-110 microM); salsoline and salsolidine were again much less effective. Since the efficient TIQ concentrations in this system are identical with those reported to generate central-nervous effects, it is concluded that certain TIQs may amplify peripheral inhibitory effects of ethanol on testicular endocrine function by their interaction with at least one enzyme of the androgen biosynthetic pathway. PMID- 1921649 TI - Heterogeneity among astroglial cells with respect to 5HT-evoked cytosolic Ca2+ responses. A microspectrofluorimetric study on single cells in primary culture. AB - The effect of 5-hydroxytryptamine (5HT) on cytoplasmic Ca2+ concentration was examined at the single cell level in astroglial enriched primary cultures from newborn rat cerebral cortex. Type 1 astroglial cells were identified and the Ca2+ indicator dye fura 2/AM was used in a microspectrofluorimetric system. Pharmacological studies indicated that the Ca2+ responses were mediated by 5HT2 receptors. Four different patterns of 5HT evoked cytosolic Ca2+ responses were identified including two different types of spike patterns and two types of Ca2+ oscillations (low amplitude and base-line spiking behaviour). In addition, cells with spontaneous Ca2+ oscillations were of two types, those responding to 5HT and those not responding to 5HT. The different responses were identified already on day 7 in culture and were followed up to day 21 with a concomitant increase in the number of responding cells, although the response patterns did not differ during culture. The triggering 5HT concentration was 1 microM. The results suggest that subpopulations of astrocytes exist with respect to 5HT2-evoked cytosolic Ca2+ mobilization. PMID- 1921650 TI - Cardiovascular actions of adenosines, but not adenosine receptors, differ in rat and guinea pig. AB - This study compared the structure-activity relationships of 16 analogues at the A1 and A2 adenosine receptors (A1AR, A2AR) of rat and guinea pig. Radioligand binding studies revealed no marked differences in the affinities of each analogue at the A1AR of brain cortex or the A2AR of brain striatum. Bioassay employing Langendorff heart preparations showed that the guinea pig is more sensitive than the rat to A1AR-mediated slowing of conduction through the atrioventricular node and, in some instances, to A2AR-mediated coronary vasodilation. That difference could reflect factors such as receptor density or efficacy of coupling to effector systems. PMID- 1921652 TI - Drug reps and doctors need each other. PMID- 1921651 TI - Selected communicable diseases in Maryland in 1990. PMID- 1921653 TI - Resource-based Relative Value Scale. PMID- 1921654 TI - Provider fee project. PMID- 1921655 TI - Inflammatory pseudotumor of the retroperitoneum. AB - A child presenting with the findings of inflammatory disease was found to have a pseudotumor of the retroperitoneum. Following surgical removal, all signs of the systemic inflammatory process resolved. These rare, benign tumors of unknown etiology must not only be differentiated from locally invasive malignant lesions, but may present with findings suggesting a chronic inflammatory disorder. PMID- 1921656 TI - Preventive therapy for tuberculosis in Maryland. AB - Maryland data substantiate the safety of isoniazid therapy in preventing tuberculosis. To eradicate tuberculosis in the U.S., private physicians must play an active role by offering preventive therapy to patients at high risk of developing the disease. PMID- 1921657 TI - Metastatic basal cell carcinoma. AB - Metastatic basal cell carcinomas of the skin are rare tumors. Early excision of the primary lesion remains the best method of treatment, although unresectable tumors can be controlled by radiation therapy. Patients with regional lymph node metastases can be managed by radical lymph node dissection, while those with systemic metastases can be palliated by a combination of chemotherapy, radiation therapy, and surgery. PMID- 1921658 TI - Mortality due to septicemia in the elderly: factors accounting for a rapid rise. PMID- 1921659 TI - Hyperemesis gravidarum treated with lorazepam. PMID- 1921660 TI - Adjuvant treatment of colorectal cancer: response to the NIH Consensus Summary Statement. PMID- 1921661 TI - Self-management of diabetes. PMID- 1921662 TI - More on the DOS vs. Unix wars. PMID- 1921663 TI - Medical informatics and health care organizations. AB - A dialogue between upper management and operational elements over an organization's informatics policies and procedures could take place in an environment in which both parties could succeed. Excellent patient care practices can exist in organizational settings where upper management is not concerned with the specifics of the medical care process. But as the medical care process itself becomes costly, complex, and part of the purview of upper management, solutions to ambiguous informatics policies and practices need to be found. As the discussion of cost determination suggests, a comprehensive "top-down" solution may not be feasible. Allowing patient care expertise to drive the design and implementation of clinical computing modules without unduly restrictive specifications from above is probably the best way to proceed. But if the organization needs to know the specifics of a treatment episode, then the informatics definitions specific to treatment episodes need to be unambiguous and consistently applied. As the discussion of Social Security numbers suggests, communication of information across various parts of the organization not only requires unambiguous data structure definitions, but also suggests that the communication process not be dependent on the content of the messages. Both ideas -consistent data structure definitions for essential data and open system communication architectures--are current in the medical informatician's vocabulary. The same ideas are relevant to the management and operation of large and diffuse health care enterprises. The lessons we are learning about informatics policy and practice controls in clinical computing need to be applied to the enterprise as a whole. PMID- 1921664 TI - The Fibonacci numbers. PMID- 1921665 TI - A new format for the medical record. AB - Over the centuries, the medical record has become stereotyped. Reconsidering the purpose and organization of this document leads me to propose a four-part format consisting of administrative data, a patient synopsis, a chronological medical record, and a detailed medical record. The patient would be identified only in the administrative data section, leaving the rest of the record available for management, outcome, and cost studies, and protecting the patient's privacy. Adoption of this four-part format would make it easier to locate information in the medical record and would facilitate computerization. If the phraseology could be standardized, the new format would also allow easier data flow from one medical record to another and permit the construction of standardized disease profiles. Data on individual patients could then be compared with standardized profiles to identify deficiencies and redundancies in patient care. PMID- 1921666 TI - Using a word processor in your office. PMID- 1921667 TI - The eighth annual directory of medical hardware and software companies. PMID- 1921668 TI - "Contraction," a definition of muscle action. PMID- 1921669 TI - Lateral meniscal cyst: arthroscopic management. AB - Thirty-six patients underwent arthroscopic cystectomy and partial meniscectomy for a lateral meniscal cyst. In two other patients, an open cystectomy was performed following a diagnostic arthroscopy. The patients were reviewed at an average of 39 months (range 8-82) after the operation, and recurrence was found in four cases. Five patients, all keen sportsmen, were dissatisfied with the operation. Four patients, with arthroscopic signs of early degenerative arthritis, were still experiencing some pain, but were able to lead a normal working and social life. Arthroscopy is safe, giving low morbidity and recurrence. In the cases treated by arthroscopy, a horizontal meniscal tear was always found. The question whether this tear and the resulting meniscal changes are traumatic or degenerative in origin still remains; and, to some extent, neither hypothesis can be readily discarded. This study supports the use of arthroscopy alone in the treatment of lateral meniscal cysts. PMID- 1921670 TI - Prophylactic lateral knee braces. AB - Since the first reported use of knee braces for prophylactic purposes in 1979, these braces have gone through a period of widespread popularity and use, followed by increasing skepticism as to their effectiveness. Early use was unsupported by significant clinical or laboratory data. Multiple studies regarding prophylactic knee braces have since been presented in the orthopedic and sports medicine literature, often with conflicting findings and conclusions. A review is presented with the purpose of educating the reader to the historical use and investigation of these braces, along with recommendations for their future. PMID- 1921671 TI - Sex, sport, and body-size dependency of hematology in highly trained athletes. AB - Blood hemoglobin concentration, hematocrit, red cell count, white cell count (WBC), and plasma ferritin concentration were measured on 1604 occasions from 706 nationally ranked athletes in 12 sports. The blood samples were taken from a forearm vein amidst periods of moderate to intense training but at least 6 h after a training session. A multiple regression model, accounting for correlations between variables and incorporating the categorical variables of sex and sport revealed the following. Each blood variable was found to be dependent on body mass index, (mass/height2, BMI), with the exception of WBC in the males. As BMI increased so did the magnitude of these blood variables (P less than 0.01). Each blood variable was also dependent on the sport (P less than 0.01), significant differences being observed between several sports in each case. Furthermore, as has been previously reported, the magnitude of the blood variables was dependent on the sex of the athlete, each being significantly greater in males (P less than 0.01), with the exception of the WBC, which was greater in females (P less than 0.01). These data indicate that the rationality of interpreting the hematology in highly trained athletes may be increased by taking BMI and sport into account, as well as gender. PMID- 1921672 TI - Healing of skeletal muscle injury: an ultrastructural and immunohistochemical study. AB - The healing of gastrocnemius muscle injury induced with a spring-loaded hammer in rats was analysed ultrastructurally and immunohistochemically. The ends of the ruptured myofibers retracted, which resulted in a central blood filled cavity. Central zone (CZ) later becomes occupied by granulation tissue scar. CZ is surrounded by a zone where myofibers are necrotized and phagocytosed by days 2-3. Complete regeneration within the preserved basal lamina (BL) cylinders takes place in 5-7 days. The regeneration of myofibers across the scar follows a pattern different from that within BL cylinders. Thin, often branched, myotubes grow out of the BL cylinders into the granulation tissue, where they extend between fibroblasts and collagen fibrils, in general oriented parallel to the preserved myofibers. The extension of the regenerating myotube seems to take place primarily by local synthesis in the growth cone. Fusing myoblasts provide nuclei, mostly along the sides but also occasionally at the tip of myotubes. Some myoblasts seem to derive from undifferentiated cells in the granulation tissue. By three weeks only a few thin myotubes had extended across the gap between the stumps of the ruptured myofibers. Growing myotubes appear to attach to the surrounding connective tissue by specialized structures, an attachment which evidently transmits contraction force across the gap, allowing use of the injured limb before the healing is complete. PMID- 1921673 TI - Fluid replacement during prolonged exercise: effects of water, saline, or no fluid. AB - This study assessed the need to replace sodium in endurance exercise less than or equal to 6 h in duration by comparing responses to fluid replacement with water, saline (25 mmol.l-1), or no fluid. Eight subjects (five male, three female) participated in three 6-h exercise trials on an electrically braked cycle ergometer at 55% VO2max, at 30 degrees C and 50% r.h. In the water (W) and saline (S) trials, sufficient fluid was ingested to balance sweat and urinary fluid losses, while in the third trial, no fluid (NF) was ingested. Plasma sodium less than or equal to 130 mmol.l-1 was a criterion for trial termination. In the NF trial, heart rate, rectal temperature, plasma sodium, plasma aldosterone, and rating of perceived exertion were all significantly higher (P less than 0.001) than during W and S, whereas plasma volume was lower (P less than 0.001). On average, subjects terminated this trial 1.5 h prior to its scheduled completion, having lost 6.4% body weight. In contrast, no significant differences between fluid replacement with W or S were detected, although the effect of time on all aforementioned variables was highly significant (P less than 0.001). Saline intake was not associated with significantly higher plasma sodium during exercise than was water intake: plasma sodium decreased significantly during both W (to 135.5 +/- 0.5 mmol.l-1) and S (to 137.3 +/- 0.7 mmol.l-1). No subject had to terminate a trial based on plasma sodium less than or equal to 130 mmol.l 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921675 TI - Lower thermic effect of a meal post-exercise in aerobically trained and resistance-trained subjects. AB - Despite the abundance of literature concerning the thermic effect of a test meal (TEM) at rest in trained and untrained subjects, there is little information available concerning the TEM post-exercise. Therefore, it was the purpose of this study to examine the metabolic response to a 763-kcal meal prior to 30 min of exercise at 50% VO2max, in aerobically trained (AT, N = 8), resistance-trained (RT, N = 8), and untrained (UT, N = 8) subjects. Mean (+/- SEM) VO2max was 60.7 +/- 2.3 ml.kg-1.min-1, 52.9 +/- 2.2 ml.kg-1.min-1 and 51.1 +/- 2.2 ml.kg-1.min-1, for the AT, RT, and UT groups, respectively. Mean (+/- SEM) percent fat was 13.7 +/- 1.2, 12.7 +/- 1.9, and 16.9 +/- 1.4 for the AT, RT, and UT groups, respectively. Post-exercise VO2 was measured by indirect calorimetry every half hour, on two nonconsecutive days (post-absorptive (PA) post-exercise and post prandial (PP) post-exercise) for 3 h. The total TEM (post-exercise PP VO2 minus post-exercise PA VO2) was 4.86 +/- 1.62, 5.22 +/- 1.80, and 9.36 +/- 5.08 I for the AT, RT, and UT groups, respectively. The TEM post-exercise was significantly lower (P less than 0.05) for the AT and RT groups compared with the UT group. Respiratory exchange ratio (R) differed significantly only during the PA post exercise condition, with the AT group exhibiting significantly lower (P less than 0.01) values compared with the RT and UT groups. PA post-exercise R for the RT group was not significantly different (P = 0.09) from the UT group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921674 TI - Pre-exercise feeding does not affect endurance cycle exercise but attenuates post exercise starvation-like response. AB - The effects of ingesting a mixed-snack food (CB), fructose (FRU), or placebo (PBO) prior to exercise (70% peak VO2) on the metabolic response during and after cycle exercise were studied in eight normal healthy volunteers with a wide range of peak VO2 (30-70 cc.kg-1.min-1). The study was designed to minimize the impact of confounding factors by using various strategies. First, the volunteers were grouped in teams with stratification by peak VO2, and the tests were randomized by a Latin-square design. Second, subjects received two acclimation trials in the cycle ergometer to diminish the effect of learning experiences and allow them to get used to the room and equipment. In addition, financial incentives were offered for team and individual endurance times. The test meals were administered 30 min prior to the beginning of exercise, and the subjects exercised to exhaustion, which was defined with clear-cut endpoints. Gas and blood samples were taken at regular intervals before, during, and for 60 min after each exercise bout. CB and FRU induced higher pre-exercise glucose and insulin concentrations. Blood lactate increased 100% with FRU ingestion. Despite these differences; endurance time, substrate, and hormone concentrations as well as rates of substrate oxidation during exercise were identical among the three conditions. During the post-exercise recovery period, PBO was associated with a starvation-like pattern of substrate utilization in which lipid oxidation was 60% greater and carbohydrate oxidation 50% less than following either CB (75 +/- 11, 248 +/- 27 mg.min-1, P less than 0.05) or F ingestion (93 +/- 4, 221 +/- 14 mg.min-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921676 TI - Urine protein excretion and swimming events. AB - To determine total urinary protein, albumin (ALB), and beta 2-microglobulin (beta 2m) excretion rates in relation to different speeds, 12 males were studied while swimming distances of 100, 600, and 2,000 m at maximal speed. Venous blood lactate concentrations rose to 16.1, 11.6, and 4.5 mmol.l-1 after the 100, 600, and 2,000 m events, while plasma volumes were reduced by 11.3, 7.7, and 5.5%, respectively. ALB urine excretion increased to 110-120 micrograms.min-1 after the 100 and 600 m swims and to 56 micrograms.min-1 after 2,000 m (resting values: 9 micrograms.min-1). In the meantime, the beta 2m excretion rate increased 21 and 10 times the resting values, respectively, for the two shorter swims, with no change for the longer one. Progressive plasma volume reduction was associated with the increase of the protein excretion rate. As evidenced by the creatinine clearance, the glomerular filtration rate did not change for the 100 m swim but dropped by 23 and 35% for the 600 and 2,000 m ones, respectively. On the other hand, the ALB clearance increases were elevated for the three swims, while the beta 2m clearance increases were inversely related to the swimming speeds. The data showed a relationship between the rate of protein excretion and the speed of the swim, and the reduction of plasma volume. The findings could indicate a renal glomerular alteration, with an additional dysfunction of the tubular reabsorption process when the exercise load is high during swimming events. PMID- 1921677 TI - Catecholamines, behavioral stress, and exercise--introduction to the symposium. PMID- 1921678 TI - Behavioral correlates of sympathoadrenal reactivity: the toughness model. AB - Research with humans is reviewed showing that increased levels of urinary epinephrine (EPI) and norepinephrine (NE) from samples taken following mental challenge/stress situations are associated with better performance in those situations and with emotional stability. Another research tradition with humans and animals shows that various training protocols lead to increased peripheral and central catecholamine capacities. Those training protocols include continuous exposure to cold, periodic exposure to some intermittent stressors such as foot or tail shock (with intervening rest periods), or programs of aerobic exercise. While increasing catecholamine capacities, those procedures also result in lower base rates of the catecholamines and with the delay of pituitary-adrenal-cortical responses in challenge/stress contexts. That physiological pattern of "toughness" leads to improved performance in challenge/stress situations, increased tolerance of stressors (i.e., reduced behavioral suppression or depression), emotional stability, and immune system enhancement. The special conditions are discussed that are required for demonstrating increased catecholamine capacities rather than the attenuation of arousal associated with increased muscular and neuroendocrine efficiency. Finally, the role played by toughness in reducing anxiety while increasing energy in challenge/stress situations is discussed. PMID- 1921679 TI - Exercise training and response to stress: insights from an animal model. AB - The effect of training on the sympathoadrenal and cardiovascular responses to stress was examined in borderline hypertensive rats (BHRs). Animals trained with swimming showed reduced heart rates and plasma norepinephrine and epinephrine levels in response to novel foot shock stress. In contrast, systolic blood pressure was significantly higher in trained BHRs during the stress. Parasympathetic blockade with atropine sulfate (1 mg.kg-1 IV) had little effect on heart rate during stress in untrained rats but significantly elevated the stress-induced heart rate of trained animals. The reduction in stress reactivity produced by exercise training is not manifested in all physiological variables and increases in parasympathetic tone contribute strongly to the attenuated reactivity in heart rate. PMID- 1921680 TI - Plasma catecholamine response to acute psychological stress in humans: relation to aerobic fitness and exercise training. AB - Existing cross-sectional studies on plasma catecholamine activity provide no support for the concept that a markedly high level of aerobic fitness modifies sympathoadrenal response to an acute psychological challenge in humans. In contrast, compromised sympathetic nervous system activity has been observed in individuals with low aerobic fitness and the relationship probably reflects a global deconditioning syndrome involving both psychological and physiological processes. The relationship between low levels of fitness and plasma norepinephrine may appear as a blunted or augmented response depending upon the nature of the task. Short-term (3-4 months) exercise training studies conducted with humans have not indicated a substantial adaptation in the relative plasma catecholamine change from a preexisting baseline during exposure to acute psychological stress. Exercise training can lower basal circulating plasma norepinephrine, resulting in lower absolute concentrations during an acute challenge, but the studies in this area lack consistency and the absolute change tends to be modest. There is no evidence that fitness or exercise training is significantly associated with plasma epinephrine activity during short-term psychological stress. PMID- 1921681 TI - Physical fitness, cognitive performance, and aging. AB - The relationship between physical fitness and cognitive performance in old age is examined in the light of contemporary capacity theories of attention. It is suggested that a model of cognition based upon the notion of a declining attentional capacity with advancing age provides a valuable conceptual framework for examining the influence of physical fitness on cognitive performance in old age. A direct prediction of the model is that cognitive tasks which require effortful processing should be more sensitive to the effects of fitness than tasks which can be performed without or with minimal attention. It is suggested that future research in the area of exercise and cognition systematically manipulate the attentional requirements of the tasks selected for the evaluation of cognitive performance. The implications of such a task-dependent association between physical fitness and cognitive performance for future research are discussed. PMID- 1921682 TI - Stress reactivity: hemodynamic adjustments in trained and untrained humans. AB - There is mounting evidence to suggest a relationship between heightened cardiovascular (CV) and sympathetic nervous system (SNS) reactivity to behaviorally stressful situations and cardiovascular pathology. Exercise training has been suggested as a non-pharmacological, therapeutic intervention technique to counter behaviorally induced CV and SNS reactivity. This approach is based on well-documented adaptations in CV and SNS functioning that result from exercise training. However, the theoretical basis for the relationship between physical fitness and stress reactivity has not been fully explored. Additionally, there are methodological and design considerations that inhibit comparison and interpretation of research studies regarding the role of physical fitness or exercise training and cardiovascular and SNS reactivity during behavioral stress. The focus of our laboratory studies has been to more fully described the CV and SNS responses to behaviorally challenging novel and learned tasks in highly fit, exercise trained, and untrained college-age males. The results from these studies suggest that highly fit and untrained males exhibit similar CV and SNS responses to a novel task. However, upon repeated exposure to the task, fit individuals exhibit attenuated mean arterial pressure and cardiac output responses. The data from the longitudinal studies suggest that there is an exercise training induced attenuation in the cardiac output response to behavioral challenge and that this is at least partially the result of an attenuated stroke volume response to the task. Thus, exercise training does appear to alter cardiovascular functioning during familiar, behaviorally challenging situations. PMID- 1921683 TI - Weight training may provide a better stimulus for increasing bone mineral content (BMC) than run and swimming training. PMID- 1921684 TI - Changes in plasma volume after prolonged endurance exercise. PMID- 1921685 TI - Prevalence of sickle cell trait in athletic West African population. PMID- 1921687 TI - [Cytologic changes in bronchoalveolar lavage in amiodarone treated patients]. AB - The histologic evidence of amiodarone pulmonary toxicity is interstitial pneumonia with foamy alveolar macrophages, which ultrastructurally show lamellar inclusion bodies due to lipid storage. Bronchoalveolar lavage (BAL) fluid findings include foamy macrophages, considered characteristic, and, in certain patients, differential cell counts suggestive of active alveolitis, giving rise to an immunologic explanation for its origin. The present study was undertaken in order to investigate the findings in BAL fluid in nontoxic patients taking amiodarone and to evaluate their clinical relevance. Eleven patients taking amiodarone chlorhydrate for severe ventricular arrhythmias (345 +/- 129 mg/day during 46 +/- 31 months and an accumulated dose of 440 +/- 337 g) and without clinical or radiological evidences of pulmonary toxicity, were clinically evaluated and studied by BAL. As shown in Table 1, cough and pulmonary rales were common findings (64% and 36% respectively), chest X-Rays were normal or indicative of cardiac failure and arterial blood gases showed slight hypoxemia (PaO2 83 +/- 10). As these are usual findings in advanced cardiac diseases, the patients were considered as having no amiodarone toxicity. BAL was done and the fluid obtained was processed for cytologic study. In every patient foamy macrophages were seen with light microscopy and lamellar bodies were detected by electron microscopy. In 5/10 evaluable patients BAL fluid cell count disclosed an increase in lymphocytes, leukocytes or both, indicative of alveolitis. This group of patient had lower PaO2 and PaO2/PAO2 than "non alveolitic" patients (76 +/- 9 mmHg vs 89 +/- 5 mmHg and 0.72 +/- 0.1 vs 0.85 +/- 0.08 - p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921686 TI - [Treatment of paroxysmal supraventricular tachycardia with a single oral doses of diltiazem and propranolol]. AB - Chronic antiarrhythmic therapy for the prevention of episodes of paroxysmal supraventricular tachycardia is limited by its elevated cost, the development of side effects and lack of patients' collaboration. In this study the efficacy and safety of a single oral dose of diltiazem (180 mg) and propranolol (80 mg) were assessed. Eighteen episodes of supraventricular tachycardia were treated in 17 patients, 9 female and 8 male, aged between 19 and 60 years old (mean 45.3 +/- 11.4). The episodes had begun 3 months to 40 years before. They were divided in 3 groups: group I (placebo), 6 episodes; group II (diltiazem-propranolol), 12 episodes; and group III (patients from the placebo group without spontaneous recovery of sinus rhythm who were given active drug), 6 episodes. There were no spontaneous conversions in group I (placebo) within 80 minutes. In group II, ten out of 12 episodes responded to the combination after 38.8 +/- 20.8 minutes (seven episodes were converted to sinus rhythm within the first 45 minutes). In group III (non-responders to placebo who were subsequently given active drugs), four out of 6 episodes were suppressed after 50.7 +/- 16.7 minutes. The cycle of the tachycardia lengthened before conversion to sinus rhythm both in groups II and III. Neither systolic nor diastolic blood pressure changed significantly in any group. Seven out of 14 patients who successfully converted to sinus rhythm in groups II and III, suffered mild to moderate sweat between 3 and 5 minutes before the end of the episodes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921688 TI - [Effects of beta-adrenergic blocking with propranolol on the mechanisms of glucose regulation in the dog]. AB - Propranolol (P) administration is known to cause hypoglycemia in insulin dependent diabetic patients. The mechanisms whereby this response is produced remain controversial. Some authors postulate an inhibition in the beta-adrenergic action of catecholamines, responsible for hepatic glycogenolysis, while others indicate that these hormones are not so important in the regulation of blood sugar (BS) level. The present studies were undertaken to assess the mechanism whereby hypoglycemia is developed in the dog, with or without beta-adrenergic blockade. Unanesthetized male mongrel dogs were used, weighing 10-20 kg body wt., fed on dog chow pellets and water ad libitum up to 18-22 hours before the test performances. The dogs were randomly grouped into two groups, A and B in which the effect of P on several hormonal and metabolic responses basally and during insulin (I) test, were respectively studied. Group A was constituted by two subgroups of 6 animals each; the animals of one subgroup were beta-blocked, receiving P p.o. for 10 days (80 mg every 8 hours); the dogs of the remaining subgroup received only P excipient in the same way as the treated ones, for the same period. As P treatment was completed, blood samples were taken by venipuncture, in a peripheral vein, at 0 and 60 min. Some biological controls of beta-blockade, assessed at 0, 30 and 60 min, indicated that mean pulse rate (+/- SE) in the control dogs was 123 +/- 2, 128 +/- 2 and 128 +/- 3 beats/min while in the P treated ones was 106 +/- 2, 103 +/- 1 and 103 +/- 3 respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921689 TI - Localized eastern equine encephalitis in Santiago del Estero Province, Argentina, without human infection. AB - In 1981, a localized epizootic of Eastern Equine Encephalitis (EEE) occurred in irrigated areas of four counties in the province of Santiago del Estero, Argentina. The diagnosis was confirmed by serology, and there was no evidence of involvement of Western or Venezuelan equine encephalitis viruses. The overall incidence of equine encephalitis was estimated 17%, the case-fatality rate at 61% and the inapparent: apparent infection ratio less than or equal to 2.9:1. This is the first localized epizootic defined in Argentina and the first in which EEE has been found as the sole etiologic arbovirus. This posed the possibility to look for human infection in the area. In spite of a careful surveillance, no evidence of human disease or infection was found, differing from the situation in USA where EEE virus is a public health problem. Nevertheless vector/s and vertebrate hosts involved in the transmission cycle in Argentina remain unknown, precluding at present speculations on the potential human risk. PMID- 1921691 TI - [Status of cerebral cortical excitability in juvenile myoclonus epilepsy]. AB - The myoclonic epilepsies constitute an heterogeneous group of entities characterized by primary generalized seizures, whose common critical manifestation is myoclonus. Within this group there is a subset of patients, identified by Janz in 1955 as "Impulsive petit mal" and later named "Janz juvenile myoclonic epilepsy" (JJME) by Delgado-Escueta. Its most important clinical features are myoclonus, expressed as mild to moderate jerks of neck, shoulders and arms. These jerks are more frequent when awakening; they can be caused by sleep deprivation and emotional stress, without consciousness impairment. Usually neurologic examinations and mental status are normal. Response to specific treatment is good, with disappearance of seizures in most patients. We attempted to assess the pathophysiologic mechanisms involved in this kind of epilepsy. The existence of differences or similarities with the findings described in the other forms of myoclonic epilepsy was specially considered. In 14 patients with JJME, we performed C reflex studies with negative results. The mean amplitude of somato sensitive evoked potential (SSEP) was around 5 microV (normal values: 2.5 microV) in its different components. Shibasaki et al. suggested that the amplitude increase could be related to a cortical excitability increase at the somatosensory and motor level, which is the probable site of the epileptogenic area. Within the patient group with myoclonic progressive epilepsy (EMP) and continuous partial epilepsy (CPE), SSPEs amplitude ranged from 8 microV to 40 microV. In our patient group, the increase in SSPEs amplitude was smaller than the one observed in the other two entities. However, it was significantly higher than the mean value for the normal population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921690 TI - [Bacterial endocarditis in patients over 60 years of age]. AB - Bacterial endocarditis (BE) is a disease difficult to diagnose and with poor prognosis in older people. A total of 76 episodes of this disease occurring in 73 patients were studied with particular attention to clinical manifestation, underlying heart disease, etiological germs, hospitalary mortality and prognosis within 6 months from diagnosis. All patients were 60 years old or older. Mean age was 72 +/- 7 years and male/female relation 1.7/1 Fever and heart murmur were present in 93% and 89% of patients, respectively; 33% of patients complained of vertebral or paravertebral pain which can be an early symptom of this disease. BE was suspected in 47% of patients at admission. Hospitalary mortality was 33% and increased to 47% within 6 months. The mean age of survivors was 71.7 +/- 7 years, versus 73.9 +/- 6 in the deceased (p = 0.08). Lack of suspicion of BE at admission was related with increased mortality (p = 0.04). The germ more frequently isolated was Streptococcus (73%). 53% of patients had some underlying heart disease. Aortic valve was involved in 50% and mitral valve in 21% of the cases. Of all the patients that in retrospect would have had indication of surgery (n = 25) 9 patients were operated, 6 during the first admission with a mortality of 17%. In those patients who were not operated, the mortality was 100% (16/16), making this difference statistically significant, p less than 0.001. PMID- 1921692 TI - [Muscular isokinetic dynamometry]. AB - In the past, muscular strength has primarily been measured using isometric, isotonic or tensiometric techniques. The advent of isokinetic dynamometers has supplied an objective method of measuring peak torque throughout a full range of motion at a predetermined speed of contraction. An isokinetic contraction is a refinement of the controlled motion concept. The isokinetic contraction is dynamic, but the speed of the motion is held constant by a special device. In this way, resistance is in direct ratio to the varying force applied through the full course of a natural movement. The purpose of this study was to determine the peak torque of quadriceps (Q), and hamstrings (H), and their biomechanical angle of production, H to Q ratio and bilateral comparisons of these variables for the first time in a Southamerican population. Twenty healthy and voluntary males (age: 21.9 +/- 3.1 years, height 193.2 +/- 6.5 cm, weight: 84.2 +/- 5.2 kgs.), were tested on the Cybex II Dynamometer and Cybex Data Reduction Computer (CDRC). Quadriceps and hamstrings peak torque (pkTQ), in Newton-meters, were obtained at angular velocities of 60, 180 and 240 degrees. sec-1. Also, the angle of the range of motion at which peak torque occurred in both directions, H and Q peak torque to body weight ratios, H to Q ratio were measured. Finally, CDRC provided the bilateral comparison of the different variables expressed in percentages. All measurements were automatically corrected for the effect of gravity. The absolute maximal pkTQ of dominant (D), and non-dominant (ND), quadriceps at 60 degrees/sec was DQ 297 +/- 25 Nwm and nDQ 303 +/- 13 Nwm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921694 TI - [Encephalopathy in an adult with Shigella]. AB - A case of sporadic shigellosis is reported. A 30 year old woman, presented neurologic dysfunction, mild watery diarrhea and fever which had started one week before her admission. Abdominal tenderness, confusion, delirium, impairment of orientation and of recent memory were found. Abnormal motor activity with rigidity, tremors, myoclonus around the mouth also existed. There were neither focal signs nor signs of meningeal irritation. Computed tomography and nuclear magnetic resonance of the brain were normal. Laboratory analyses did not explain the anomalies. Several deep ulcers were disclosed by colonoscopy and a S. flexneri was isolated from the material extracted by endoscopy. Nonspecific colitis was informed by pathology. The patient was treated with 400 mg ciprofloxacin for 14 days, with improvement of the clinical picture. The most prominent aspect in this case was the clinical presentation with predominant neurologic symptoms creating the impression of a primary nervous system disease. Admission diagnosis was viral encephalitis. We believe that all of the anomalies present in our patient, the diarrhea and encephalopathy, were produced by the same etiologic agent, S. flexneri and by its toxins. PMID- 1921693 TI - [Adjunctive treatment with hyperbaric oxygen in a patient with rhino-sinuso orbital mucormycosis]. AB - Mucormycosis (phycomycosis) is an acute and often fatal infection, mostly seen in diabetics and immunocompromised patients, and seldom in healthy people. Therapy includes aggressive surgical debridement, amphotericin B and control of underlying predisposing condition (diabetes, immunosuppression or immunodeficiency). The rhino-sinuso-orbital presentation is typically observed in insulin-dependent diabetes mellitus with ketoacidosis. This metabolic condition may impair the polymorphonuclear function in a reversible way and this may favour infection by a mucoral. These spores germinate into hyphae, which invade local arteries and arterioles, causing thrombosis, vascular insufficiency and tissue hypoxia and acidosis, conditions which further enhance fungal growth. Hyperbaric oxygen has theoretical value in treating mucormycosis, since it reduces tissue hypoxia caused by the vascular insufficiency. We report an insulin-dependent diabetic patient with rhino-sinuso-orbital mucormycosis, who after being treated with amphotericin B and surgical debridement on two occasions, maintained clinical and tomographic evidence of active infection, and mucoral persistence in the lesion. An aggressive surgical debridement, using microsurgical techniques, was performed. Amphotericin B was increased up to a total dose of 3900 mg. (he had previously received 2900 mg) and hyperbaric oxygen was added as adjunctive treatment. The outcome was successful. There was no evidence of relapse after a 16-month follow-up. This observation would confirm the usefulness of hyperbaric oxygen as adjunctive therapy in mucormycosis. PMID- 1921696 TI - [Immunotherapy: new strategies to enhance the immune response in tuberculosis]. PMID- 1921695 TI - [Introduction to positron emission tomography]. PMID- 1921697 TI - [Medicine, patients and numbers]. PMID- 1921698 TI - [Platelet antiaggregation in cerebrovascular diseases]. PMID- 1921699 TI - [Cardiovascular effects of aspirin]. PMID- 1921700 TI - [Renal function pre and post extracorporal shock wave in mononephric patients with staghorn lithiasis]. PMID- 1921701 TI - [Latent HTLV-I and HIV-1 infection in seronegative subjects with risky behavior in Argentina]. PMID- 1921702 TI - [TSH receptor antibodies as a recurrence index of Graves disease treated with antithyroid drugs]. AB - TSH receptor antibodies (TRAb) measured by the TBI residual assay (TBIr) were studied in 3 groups of Graves disease patients, as follows: 54 non treated cases (Group 1), 20 cases under methimazol treatment (Group 2) and 23 patients who were euthyroid after one year of methimazol treatment (Group 3), in order to evaluate the usefulness of TBIr as a recurrence index in Graves disease following antithyroid drug treatment. In group 1, TBIr was positive in 77.7% (45/54) of the cases. In group 2: 45% (9/20) had positive values for TBIr, all of which had a recurrence of disease during the year following the suppression of the treatment. In group 3, 69.5% patients (16/23) were TBIr positive. In 75% (12/16) of them the abnormally high values of TBIr predicted the recurrence, while 71.43% (5/7) of the patients, TBIr negatives, continued the remission 12 months later. By comparing the TBIr values before and after treatment in the group 3 patients, different possibilities were observed: a) TBIr persistently elevated: 52.17% (12/23). The 83.3% (10/12) had a recurrence before 6 months following treatment termination. b) TBIr, initially elevated, but later showing 50% decrease or negative values: 26.09% (6/23). Every patient was euthyroid one year after the treatment ended. c) TBIr persistently negative: 13.04% (3/23). Two of them had recurrence of their disease. d) TBIr negative which changed later to positive: 8.70% (2/23). Both presented a recurrence. In accordance with these results, we believe that abnormally high TBIr values before or after treatment is a useful recurrence index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921704 TI - Leiomyosarcoma of the inferior vena cava. Experience with 7 patients and literature review. AB - Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant tumor originating in the smooth muscle of the media. Although rare, it is the most common malignancy in the IVC. One hundred and six cases have been reported thus far in the world literature, usually as isolated case reports. Clinical, radiologic, and therapeutic management and follow-up, including 7 additional cases, have been reviewed and summarized. Clinical manifestations are dependent upon the location of the tumor. The main symptom was a palpable mass for a tumor in segment I, abdominal pain for segment II, the presence of Budd-Chiari syndrome for segment III. Segment II was the most frequent site of leiomyosarcoma of the IVC, alone (n = 41) or with other segments (n = 39). Before laparotomy, clinical recognition was difficult or impossible. Recently, however, newer imaging modalities including ultrasound and CT scan have permitted earlier diagnosis. Metastases, when diagnosed, were either present at diagnosis (n = 20) or appeared as the disease progressed (n = 18). Metastatic disease frequently involved the liver, lung, lymph nodes, or bone. The small number of patients alive without metastases (16/113) must be analyzed all the more carefully because these patients were followed for less than 2 years. When prolonged follow-up is possible, the number of patients alive without neoplastic disease is significantly reduced. We found the prognosis of patients with LMS of the IVC to be poor. Diagnosis was made at autopsy for 27 patients. Among the 86 patients with follow-up information, 59 died within a mean of 16 months, and 26 were alive 25 months after the diagnosis. The main prognostic factor is topography, particularly the highest level of extension of the tumor. The upper-segment tumors have the poorest prognosis. The best therapeutic management is difficult to recommend because most of the cases in the literature did not include a sufficient follow-up. Given the very small number of patients completely free of neoplastic disease after sufficient follow-up, it seems unlikely that leiomyosarcoma of the IVC can now be cured. Patients who received a combination of surgery, radiotherapy and chemotherapy remained free of disease for longer periods. The unanswered question is: what is the best timing for each of these treatments? We recommend diagnosis of leiomyosarcoma of the IVC through biopsy guided by ultrasonography or computed tomographic scan. Therapeutic management should include large doses of chemotherapy preoperatively with or without radiotherapy to reduce tumor size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921703 TI - Purpura fulminans and symmetrical peripheral gangrene caused by Capnocytophaga canimorsus (formerly DF-2) septicemia--a complication of dog bite. AB - We review the syndrome of Capnocytophaga canimorsus (DF-2) septicemia after exposure to dogs or cats. We describe a previously healthy patient who developed diffuse intravascular coagulation and symmetrical peripheral gangrene as a result of C. canimorsus septicemia after a dog bite. To our knowledge, this patient was the first to receive combined plasmapheresis and leukapheresis for C. canimorsus septicemia. Symmetrical peripheral gangrene is frequently associated with C. canimorsus septicemia and may lead to an early diagnosis in patients who become severely ill after a dog bite. Other complications include arthritis, meningitis, and endocarditis. These manifestations can also be found in previously healthy patients, although a prior splenectomy or other causes of impaired host defense clearly enhance the risk. Prompt treatment with penicillin G is required. PMID- 1921706 TI - Evolution of ribosomal RNA gene copy number on the sex chromosomes of Drosophila melanogaster. AB - A diverse array of cellular and evolutionary forces--including unequal crossing over, magnification, compensation, and natural selection--is at play modulating the number of copies of ribosomal RNA (rRNA) genes on the X and Y chromosomes of Drosophila. Accurate estimates of naturally occurring distributions of copy numbers on both the X and Y chromosomes are needed in order to explore the evolutionary end result of these forces. Estimates of relative copy numbers of the ribosomal DNA repeat, as well as of the type I and type II inserts, were obtained for a series of 96 X chromosomes and 144 Y chromosomes by using densitometric measurements of slot blots of genomic DNA from adult D. melanogaster bearing appropriate deficiencies that reveal chromosome-specific copy numbers. Estimates of copy number were put on an absolute scale with slot blots having serial dilutions both of the repeat and of genomic DNA from nonpolytene larval brain and imaginal discs. The distributions of rRNA copy number are decidedly skewed, with a long tail toward higher copy numbers. These distributions were fitted by a population genetic model that posits three different types of exchange events--sister-chromatid exchange, intrachromatid exchange, and interchromosomal crossing-over. In addition, the model incorporates natural selection, because experimental evidence shows that there is a minimum number of functional elements necessary for survival. Adequate fits of the model were found, indicating that either natural selection also eliminates chromosomes with high copy number or that the rate of intrachromatid exchange exceeds the rate of interchromosomal exchange. PMID- 1921705 TI - Human immunodeficiency virus infection in North American women: experience with 200 cases and a review of the literature. AB - This study was designed to define the epidemiology and natural history of human immunodeficiency virus (HIV) infection in women in Rhode Island. Two hundred women referred to Brown University physicians from 1986 through 1990 were evaluated at 3-to-6-month intervals for 12 to 60 months. All received antiretroviral therapy and prophylaxis against opportunistic infections when indicated on the basis of CD4 lymphocyte counts. Major findings included: 1) rapid shift of dominant mode of transmission from intravenous drug sharing to heterosexual route; 2) significant gender-specific differences in clinical presentation; 3) increased frequency of cervical dysplasia in women infected via intravenous needle sharing; 4) no definite gender-specific differences in progression of HIV infection; 5) enormous societal impact of HIV infection in women. Principal conclusions are: 1) rapid change to predominantly heterosexual HIV transmission can occur in North America, with serious societal impact; 2) gender-specific clinical features can lead to earlier diagnosis of HIV infection in women; 3) HIV infection in women does not pursue an inherently more rapid course than that observed in men. PMID- 1921708 TI - An extreme codon preference strategy: codon reassignment. AB - We argue that in animal mitochondria codon reassignments, such as those for AGA and AGG from arginine to serine or of AUA from isoleucine to methionine, are the result of an interplay between biased mutational forces and selective ones. In particular, there is a marked tendency for animal mitochondria to have very small genomes and to minimize their investment in components required for gene expression. These tendencies are expressed as a reduction in the diversity of tRNA isoacceptor species. In our view, the pressure to simplify tRNA populations, together with mutational bias against certain codons, will account for the codon reassignments observed in animal mitochondria. A parallel to the major codon bias in microorganisms, which likewise tends to reduce the diversity of the tRNA isoacceptor populations under fast growth conditions, may be drawn. Therefore, we suggest that codon reassignments are usefully viewed as an extreme form of codon bias. PMID- 1921707 TI - Molecular evolution of the mammalian ribosomal protein gene, RPS14. AB - Ribosomal protein S14 genes (RPS14) in eukaryotic species from protozoa to primates exhibit dramatically different intron-exon structures yet share homologous polypeptide-coding sequences. To recognize common features of RPS14 gene architectures in closely related mammalian species and to evaluate similarities in their noncoding DNA sequences, we isolated the intron-containing S14 locus from Chinese hamster ovary (CHO) cell DNA by using a PCR strategy and compared it with human RPS14. We found that rodent and primate S14 genes are composed of identical protein-coding exons interrupted by introns at four conserved DNA sites. However, the structures of corresponding CHO and human RPS14 introns differ significantly. Nonetheless, individual intron splice donor, splice acceptor, and upstream flanking motifs have been conserved within mammalian S14 homologues as well as within RPS14 gene fragments PCR amplified from other vertebrate genera (birds and bony fish). Our data indicate that noncoding, intronic DNA sequences within highly conserved, single-copy ribosomal protein genes are useful molecular landmarks for phylogenetic analysis of closely related vertebrate species. PMID- 1921709 TI - [Chemical safety (IV)--legal basis for control]. AB - This work reviews the legal regulations constituting the basis for control of chemical substances present in the working and natural environment as well as in food and utility products in Poland. It has been found that there are many regulations which comply with legislative needs. However, a lack of general regulation on the protection of human health and the environment against the noxious effects of chemicals is widely acknowledged. The unsatisfactory condition of human health and environment in Poland may be attributed to the fact that the existing standards are often disregarded. The authors are of the opinion that implementation of an organizational and legal system of chemical safety would be an important step towards improving the existing situation. PMID- 1921710 TI - [Estimation of physical exertion by the AET ergonomic job description]. AB - The study has been aimed at showing the advantages of using the AET ergonomic job description for estimation of physical workload, as compared to the traditional methods in which the estimates are made on the basis of the value of energy expenditure, static load and motion monotypicity. From tests on employees at 28 workposts it has been found that by analysing 17 factors involved in the overall estimate of physical workload according to AET, it is possible to characterize the work more precisely. The results of the tests indicate that AET estimates of heavy dynamic work are strongly correlated with the size of energy expenditure, whereas the estimation of body position--with the estimate of static load and the frequency estimate--with the estimate of motion monotypicity. New possibilities, with regard to the traditional method of physical workload estimation, are opened up by the AET method in relation to light dynamic work and static effort. The physical workload rate, calculated according to the AET method as the total of 17 elements estimated, does not differentiate the values of the workloads at individual workposts and, therefore, requires physiological verification. PMID- 1921711 TI - [Static changes of the spine in workers in the automobile industry]. AB - In 13 year period of time 28.324 x-ray examinations of spine performed in workers of Jelcz's car-factory revealed a high percentage (22.5%) of vertebral epiphysitis (Scheuermann's Disease) and scolioses (9.95%) among adolescents aged 17-21 years applying for work in the factory. The statistical analysis of this material has shown that vertebral epiphysitis passed by persons at the age below 40 years has contributed to static changes in spine more significantly than the character of work performed. The greatest number of scolioses among workers aged over 40 years was noted in: tinsmiths, pressers and welders--i.e. the jobs exposing the spine to the highest loads. In those professional groups periodical examinations are recommended to detect early symptoms of scolioses. PMID- 1921712 TI - [Evaluation of the nervous system in workers of a enolofos production department in chemical factories]. AB - Neurological examination including EEG, ENG and measurement of nerve motor conduction velocity were performed in 41 male workers, exposed to enolofos. 43% of the population examined developed subjective neurological symptoms 34%- discrete lesions of CNS and in 31% polineuropathy was observed. Motor nerve conduction velocity was decreased in 10 workers (24%) in peroneus nerves and in 1 worker in ulnaris nerve. Comparison of EEG and ENG with the control group was not statistically significant. PMID- 1921713 TI - [Examination of reaction time--auditory brainstem responses--ABR in noise induced temporary and permanent threshold shift]. AB - This study was conducted to investigate the differences between auditory brainstem responses--ABR recorded in men with temporary or permanent threshold shifts (TTS or PTS). Behaviorally, the tested ears showed insignificant differences in the hearing thresholds at frequencies in the range 0.25-8 kHz. The latency of waves I, III, V and interwave intervals I-III, III-V, I-V were analysed as functions of stimulus intensity. The comparisons between recordings obtained in groups with TTS and PTS showed significant differences in latencies of wave V at 90 dB nHl only. The latencies of waves I, III and interwave intervals were unaltered. PMID- 1921714 TI - [Mortality analysis of the working age population in Poland. Part II. Percentage of main causes of death in the growing mortality rate of men and women]. AB - This work presents an analysis of mortality rates among men and women aged 20-64, by the main causes of death and the places of habitation during the years 1951 1985. Over the investigated period, the percentage of deaths from cardiovascular system diseases, neoplasms, traumas and poisonings among the persons belonging to the professionally active age group increased to ca 80%. The growing trend of deaths in that group was much higher among men than women. This was especially true about the cardiovascular system diseases and malignant neoplasms. Evaluation of mortality rates during the last 20 years by death causes (allowing for age and place of habitation) indicates that the greatest increase of deaths occurred in the group of men aged 40-59 living in the rural environment. PMID- 1921715 TI - [Changes in the parameters of sickness absenteeism analysed over a 20 year period]. AB - Sickness absenteeism increase in a given industrial plant within homogeneous employee groups may be due to: increased incidence, increased duration of absences, and increased frequency of obtaining the certificates of temporary work disability in some determined diseases. The study involved the same plant in which studies during the sixties and the seventies had been performed. The purpose of the study was to determine which of the parameters was responsible for the changes in absenteeism rate during the period 1967-1987. The analysis showed that the sickness absenteeism increase in the plant over the 20-year period discussed was 46% in men and 40% in women. The increase resulted from increased average duration of absence from ca 7 days to ca 11 days. The increase of the average number of the days of absence per one sick person was ca 9 days per year. Taking into account the employees' age it is to be noticed that in the youngest groups the increase of sickness absenteeism rate among young men was accompanied by an increase in the number of cases per one sick person per year, whereas the increase in the rate of sickness absenteeism among young women resulted also from the increase of the percentage of absentees. In those groups there was also observed an increase of average duration of absence over the same period. PMID- 1921716 TI - [Exposure to carcinogens in industry. Evaluation of the situation and proposition of an information system]. AB - This article presents an estimate of occupational exposure from carcinogens in the industrial plants belonging to the former departments of chemistry and light industry. The occurrence of 13 compounds listed as carcinogens in the list prepared in 1985 by the Chief Sanitary Inspector and 40 substances suspected of carcinogenic effects on the basis of the list prepared by the Institute of Occupational Medicine was taken into account. In the industries mentioned, 11 thousand persons were found to be exposed to the factors considered to be carcinogenic. The most numerous group constituted the employees working in contact with benzene (50%), vinyl chloride (19%), polycyclic aromatic hydrocarbons (17%) and asbestos (11%). A system of collection, analysis and qualitative evaluation of the information on exposure to those factors is necessary to enable efficient control of exposure to those factors. Basing on the experiences gained in the course of data collection and verification, the guidelines and documentation for "A System of Information on Carcinogenic Substances" presented in this article, have been prepared. PMID- 1921717 TI - [The role of testing DNA adducts and proteins in monitoring cancer risk]. AB - This paper is a review of methods used for determination of adducts of chemicals or their metabolites with DNA of different cells or with blood proteins in humans and animals. Advantages and disadvantages of methods currently used have been discussed. The relationship between adducts formation and genotoxic, mutagenic and carcinogenic properties of chemicals has been shown. An attempt was made to indicate the usefulness of DNA or protein adducts monitoring in humans to detect their exposure to carcinogenic substances and to assess the risk of cancer. PMID- 1921719 TI - Ophthalmic findings in maple syrup urine disease. AB - Maple Syrup Urine Disease is an autosomal recessive disorder of branched chain amino acid metabolism with an incidence in Ireland of one in 140,154 births. Ocular complications in untreated or late diagnosed patients includes optic atrophy, grey optic papilla, nystagmus, ophthalmoplegia, strabismus and cortical blindness. Seven patients with maple syrup urine disease were studied. All were diagnosed with the aid of newborn screening and commenced on early dietary treatment (mean age at diet introduction = 5 days). All remain physically well, with average intellectual performance, three having minor neurological defects and one strabismus. Early diagnosis, proper therapy and subsequent vigilant management may reduce substantially the risks of ophthalmic complications in this rare disease. PMID- 1921718 TI - [Latex immunologic methods of determining micro-molecular proteins and albumins in urine. Part I. Description of the method]. AB - The most frequent markers of early kidney dysfunction include determination of micromolecular proteins, such as beta 2-microglobulin (beta 2M), retinol-binding protein (RBP) and albumins (Alb), in urine. The determination of those proteins in urine is carried out by means of immunological methods. The latex immunological methods (LIA), allowing to avoid the use of radioisotopes and relatively cheap one as compared with ready-made proprietary kits, may prove to be particularly useful in Polish laboratories. The LIA method in routine tests of protein content in urine was practically assessed. Reproducibility of the method was verified under the conditions of international quality control. PMID- 1921720 TI - An unusual presentation of diabetes mellitus. AB - Three middle-aged and elderly patients presenting with their first attack of acute anterior uveitis (AAU) were found to have previously undiagnosed diabetes mellitus. A first attack of AAU is unusual in this age group and may indicate underlying systemic disease. Diabetes is an infrequent cause of uveitis but should be considered in the differential diagnosis. It is important to be aware of this uncommon presentation of the disease, thereby stating the value of performing routine urinalysis in AAU. PMID- 1921721 TI - Essential thrombocythemia: a rare case of central retinal artery occlusion. AB - Essential thrombocythemia is a myeloproliferative disorder with an increased amount of abnormal platelets, causing both hemorrhagic and thrombotic pathology. Some of its systemic complications include deep vein thrombosis, pulmonary emboli, myocardial infarcts, and renal vessel thrombosis among others. We present the rare case of a woman suffering from essential thrombocythemia with the sudden loss of vision in her right eye, caused by central retinal artery occlusion. A possible connection between these two disorders is discussed. PMID- 1921722 TI - Neovascular glaucoma, endophthalmitis and evisceration. AB - A retrospective study of 35 patients undergoing evisceration at Moorfields Eye Hospital, London between 1982 and 1987, revealed that 60% were known to be suffering from neovascular glaucoma, the majority as a result of a central retinal vein occlusion. 76% of these rubeotic eyes subsequently developed an endophthalmitis and required evisceration. 81% of this rubeotic, infected group were being treated with topical steroids prior to developing a suppurative keratitis and ensuing endophthalmitis. Every patient (9) with neovascular glaucoma that was debilitated (due to a variety of underlying medical conditions- 4 were diabetic) developed an endophthalmitis and 78% of these were also using topical steroids. This study reveals that there may be a specific group of patients with absolute neovascular glaucoma, i.e. being debilitated and using topical steroids, who might appear to be susceptible to developing severe intraocular infection. PMID- 1921723 TI - Cataracts associated with inborn errors of metabolism: a diagnostic aid. AB - Inborn errors of metabolism are a substantial field of medicine. Although genetic syndromes associated with cataracts are rare, they are important since early detection and effective treatment of visual handicaps is one of the most urgent duties of any practitioner and pediatrician. Cooperation among pediatricians, ophthalmologists, orthoptists and geneticists, as well as the institution of a high-risk registry for visual handicaps appears to be of paramount importance. PMID- 1921724 TI - Mental health services of the Veterans Administration, United States, 1986. AB - The mental health services of the Veterans Administration (VA) form an important component of the organized mental health care delivery system in the United States. The 140 VA organizations delivering mental health care represented 3 percent of all mental health organizations in the U.S. in 1986, but accounted for approximately 11 percent of the average daily inpatient mental health census and 8 percent of outpatient mental health visits in organized settings. Their 33,000 full-time equivalent (FTE) staff and $1.4 billion in expenditures devoted to mental health care were approximately 7 percent of the respective totals for all mental health organizations. Between 1983 and 1986, the number of VA organizations offering mental health care increased by only 1, but inpatient mental health additions increased by 22 percent. Average length-of-stay for these inpatients declined by almost as much. Outpatient mental health additions increased by 30 percent, and FTE staff in VA mental health services grew by 10 percent. Mental health services were provided by VA organizations in all States except Alaska, Hawaii, Montana, and North Dakota in 1986. (Veterans are free to make use of programs outside their State of residence.) The largest numbers of mental health services, additions, and episodes were found in States with very large populations, such as California, New York, and Texas. However, the highest rates of additions and episodes per 100,000 civilian population were generally in States with small populations, and often in rural States. For example, Maine, South Dakota, Wyoming, and West Virginia were among the States with the highest rates of additions and episodes. Reflecting the composition of the total population in VA facilities, of 315,630 in VA mental health services, over 95 percent were male, a relatively large percentage (17 percent) were 65 or over, and very few were under 18 years old. About two-thirds were white, non-Hispanic; one-fourth were black, non-Hispanic; and 8 percent were Hispanic. About one-sixth were suffering primarily from drug or alcohol abuse; almost all the rest suffered primarily from mental illness. In November 1986, approximately 36,000 staff persons worked in VA mental health services. About 84 percent of these worked full-time; 9 percent, part-time; and 7 percent, as trainees. The staff included approximately 2,800 psychiatrists, 700 other physicians, 1,600 psychologists, 1,800 social workers, and 7,200 nurses. Three-fourths of the expenditures for VA mental health services went for staff, with other operating expenses consuming most of the remainder. PMID- 1921725 TI - Direct-care staff: a neglected priority. PMID- 1921726 TI - Assessment of musical aptitude in people with mental disabilities. AB - Although there has been a long history of attributing different types and degrees of musical sensitivity to individuals with handicaps, actual documentation of the distribution and nature of musical aptitude is sparse. There is almost no normative information about the relative importance of various personal characteristics associated with disability, such as diagnostic category. We also know little about the relative aptitude for different musical components, especially melody and harmony. Directions for future research were suggested. PMID- 1921727 TI - Comparative survey of drug use in a community service system. AB - Drug use patterns in Colorado's community services system were surveyed. A psychotropic drug use rate of 18.6% in a reporting population of 1,282 persons compares favorably to rate reported elsewhere in the literature as well as to rates concurrently used in the state's institutional settings. Substantial experience with psychotropic and anti-convulsant medications across all residential settings were observed. Drug combinations and psychiatric diagnoses were also reported for the population surveyed. PMID- 1921728 TI - Reinforcing staff performance in residential facilities: a survey of common managerial practices. AB - A national survey was conducted to investigate how managers in public residential facilities for persons with mental retardation attempt to reinforce work performance of direct-care staff. The reinforcement procedure reported most frequently by 460 managers was performance feedback (as opposed to monetary increments and time off). Essentially all managers reported using feedback, and virtually all of them reported that feedback was effective to varying degrees as a means of reinforcing staff performance. In response to an open-ended question regarding other procedures for reinforcing staff performance, they most frequently reported increasing staff involvement in management decision-making. Results were discussed in light of future research needs for improving staff work performance and incorporating results of management research into routine management practices. PMID- 1921729 TI - Improving accuracy in documentation of restrictive interventions by direct-care personnel. AB - Accurate and reliable documentation of rights restrictions is critical for evaluating a program's success against the intrusiveness of a behavioral intervention, complying with regulatory standards, and refining treatment strategies. Direct-care and ancillary staff in three cottages at a state facility for persons with mental retardation were selected to evaluate a revised documentation system, including a new form, inservice training for staff inservice, and staff feedback, that was implemented sequentially across cottages. Results showed an immediate and sustained reduction in documentation errors following the implementation of the documentation system. Benefits and limitations of the new system were discussed. PMID- 1921730 TI - Descriptive analysis of interactions between co-workers and supported employees. AB - Varying types of interactions between workers without handicaps and supported employees were described. Results indicated that co-workers interacted extensively with persons who had mental retardation. Surprising findings included high levels of advocacy between co-workers and persons with severe or profound mental retardation and a relatively high percentage of co-workers assuming evaluation and training roles. Results were discussed in relation to the work behavior literature, which indicates that, in general, co-workers provide considerable natural support for employees across work environments. PMID- 1921731 TI - Life in the community: four years after the closure of an institution. AB - Life experiences of 18 people 4 years after deinstitutionalization were examined. The ecological approach included observation in people's homes, interviews with the 18 individuals and people in their social networks, and a survey of other service providers. Because this research was a follow-up to an earlier study of the process of closing an institution, the findings are particularly significant for future institution closures and individual planning practices. Three major implications were noted: (a) the need to treat deinstitutionalization as a process; (b) the need to pursue alternatives to the 4- or 5-bed group home, which currently dominates community residential services; and (c) the need for community-based support services to develop new, more effective approaches to community integration. PMID- 1921732 TI - Assessment of needs of adults with developmental disabilities in skilled nursing and intermediate care facilities in Illinois. AB - Findings are reported from a statewide assessment of the habilitation, medical, and behavioral training needs of adults with developmental disabilities in Illinois general nursing homes. Only 10% were determined to be appropriately placed in medical settings, and only 27% were enrolled in developmental training programs. A large proportion of those recommended for alternative residential settings had significantly more intense medical, adaptive behavior, self-care, and self-preservation needs than did residents who typically reside in residential facilities for persons with developmental disabilities. Historical barriers to addressing the residential and active treatment needs of the assessed residents were discussed as were recent program developments in Illinois and implications of this study for other states. PMID- 1921733 TI - Clinical and endometrial effects of oestradiol and progesterone in post menopausal women. AB - This study reports the clinical effects in a group of post-menopausal women after 4 months of treatment with 2 mg micronized 17 beta-oestradiol (E2) in combination with different doses of micronized progesterone (50, 100 or 200 mg) for 25 days each month. The 30 participants were divided into three groups. All of the subjects tolerated the preparation well and obtained relief from their climacteric complaints. None dropped out because of side effects and no changes were observed in blood pressure, weight or Papanicolaou cytology. Breakthrough bleeding was noted in the first cycle, mainly in the group receiving the lowest dose of progesterone. Endometrial biopsies performed before and after 4 months of treatment showed an atrophic endometrium in most of the women who received 100 mg progesterone and in all of the women on 200 mg progesterone. The results showed that this new combination of 2 mg E2 and micronized progesterone in different doses was both effective and well accepted. PMID- 1921734 TI - Androgen production by epithelial ovarian tumours in post-menopausal women. AB - Peripheral serum concentrations of androstenedione (A) and testosterone (T) were measured in 31 post-menopausal women with epithelial ovarian tumours (12 cancer, 5 borderline malignant and 14 benign tumours), and in 20 post-menopausal women who were free from ovarian neoplasms. The levels of these androgens were also measured in ovarian venous blood in 17 women with ovarian tumours. No significant differences were found between the mean serum androgen levels in patients with malignant, borderline malignant or benign ovarian tumours or the control group. The measured levels of A and T in peripheral and ovarian venous blood were highest in women with mucinous ovarian tumours. Histopathological examinations of the ovarian tumours showed hyperplasia or luteinization in ovarian tumour stroma in 5 out of 17 cases (3 mucinous tumours, 1 endometrioid adenocarcinoma and 1 serous adenocarcinoma). The results indicate that of all epithelial tumours mucinous ovarian tumours most often demonstrate hormonal activity and that malignancy has no effect on hormonal activity. PMID- 1921736 TI - Vaginal immunoglobulin A (IgA) levels in post-menopausal women: influence of oestriol therapy. AB - The concentration of secretory immunoglobulin A (IgA) in the vaginal fluid of 20 untreated post-menopausal women (aged 75.4 +/- 1.4 years) was compared with the levels in a group of 20 post-menopausal women (aged 73.2 +/- 1.5 years) treated with oral oestriol (E3) (2 mg/day) and a further group of 20 healthy, non pregnant, fertile women (aged 28.2 +/- 1.8 years). Secretory IgA was determined using a paper disc modification of the single radial immunodiffusion technique. The vaginal concentration of IgA in the untreated women was 41.5 +/- 5.7 mg/l, which was higher than that recorded in those treated with E3 (20.8 +/- 5.7 mg/l, P less than 0.05) and in the fertile women (16.4 +/- 3.7 mg/l, P less than 0.01). Epithelial cells predominated in the wet smear preparations obtained from the women who received E3 and the fertile women, while a predominance of leucocytes was observed in the untreated women. Lactobacilli were found more frequently in the vaginal flora of the women in the E3 group (P less than 0.001) and the fertile women (P less than 0.001) than the untreated group. Faecal-type bacteria were seen more frequently in the vaginal flora of the untreated women than the E3 group (P less than 0.01) or the fertile women (P less than 0.001). The possible implications of the present findings with regard to the individual variation in the intensity of symptoms experienced by women suffering from the oestrogen deficiency syndrome are discussed. PMID- 1921735 TI - Breast cyst fluid concentrations of beta-endorphin, steroids and gonadotrophins in premenopausal women with gross cystic disease. AB - Breast cyst fluid (BCF) and plasma levels of beta-endorphin (beta-EP), oestradiol (E2), progesterone (P), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), prolactin (PRL) and cortisol were assayed radiochemically in a group of 10 premenopausal women aged 45-50 years suffering from gross cystic breast disease. The concentration of beta-EP (fmol/ml) in BCF (17.6 +/- 4.6 S.E.) was over four times higher than that in plasma (4.2 +/- 0.5 S.E.). The level of E2 was 41 times higher (1738.2 +/- 350.5 S.E. pg/ml) and that of P was 47 times higher (65.47 +/- 8.25 S.E. ng/ml) in BCF than in plasma. The significantly increased values of beta-EP, E2 and P in BCF and the identification of beta-EP in the cyst-lining epithelium indicated that local synthesis occurs. Growth factor-like properties of beta-EP and E2 are responsible for the propagation of cystic changes. The autonomous formation and activity of beta-EP, E2 and P in cystic formations were not correlated with LH, FSH, TSH and cortisol levels, which were significantly higher in plasma than in BCF. The concentration of PRL in BCF was not significantly higher than that in plasma. Moreover, the plasma concentrations of testosterone, androstenedione, thyroxine, triiodothyronine, thyroxine-binding globulin and sex-hormone-binding globulin were within the normal ranges. In this study we demonstrated synergism between beta-EP and steroid hormones which encourages the development of gross cystic disease in premenopausal women. PMID- 1921737 TI - Short-term effects of Org OD 14 and 17 beta-oestradiol on bone and lipid metabolism in early post-menopausal women. AB - The effects of 8 weeks of daily oral treatment with 1 mg 17 beta-oestradiol (E2), 2.5 mg Org OD 14 [7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20 yn-3-one) , a steroid with weak androgenic, weak oestrogenic and weak progestational activity, or placebo on calcium and lipid metabolism were compared in 21 healthy, early post-menopausal women in a randomised double-blind study. The treatment period was followed by a treatment-free period of 8 weeks to study the reversibility of drug-induced effects. The results show that both E2 and Org OD 14 reduce bone resorption, as indicated by the decreases in the urinary hydroxyproline/creatinine and calcium/creatinine ratios in 2-h fasting urine. In contrast to E2, Org OD 14 did not reduce serum calcium levels. As regards lipid parameters, E2 reduced the concentration of serum cholesterol and Org OD 14 decreased serum levels of high-density-lipoprotein cholesterol and triglycerides. All these effects appeared to be reversible after cessation of treatment. It is concluded that both of these steroids reduce bone resorption in early post menopausal women, but that their mechanisms of action are most likely different. PMID- 1921738 TI - Non-linear increase in vertebral density induced by a synthetic steroid (Org OD 14) in women with established osteoporosis. AB - The results of a 2-year placebo-controlled study in 38 female patients with osteoporosis are presented. This study was conducted to evaluate the efficacy of a daily oral dose of 2.5 mg Org OD 14 ((7 alpha, 17 alpha)-17-hydroxy-7-methyl-19 norpregn-5(10)-en-20-yn-3-one) in the treatment of established osteoporosis. Org OD 14 is a steroid which shows combined weak oestrogenic, androgenic and progestational activity. A total of 31 patients completed a 12-month study period (17 placebo, 14 Org OD 14) and 25 of these went on to complete the full 24-months (15 placebo, 10 Org OD 14). A significant increase in bone mineral density as measured by dual photon absorptiometry was recorded in the lumbar spine in the Org OD 14-treated patients at 8, 16 and 24 months. The gain in bone mass after 8 months averaged 4% (P less than 0.01) and after 24 months 8% (P less than 0.001). In the control group, a bone loss rate of 2% per year was recorded in the lumbar spine. No significant changes in bone density in the forearm as assessed by single photon absorptiometry were found in either group. The increase in spinal bone density in the Org OD 14 group was non-linear and followed an S-shaped upward pattern. Org OD 14, while inducing no appreciable endometrial stimulation, was found to be a bone-active compound with anti-resorbing as well as anabolic activity. Org OD 14 warrants consideration not only for the long-term prevention of bone loss but also for curative treatment of post-menopausal osteoporosis. PMID- 1921739 TI - Efficacy of sustained-release vaginal oestriol in alleviating urogenital and systemic climacteric complaints. AB - In a double-blind, placebo-controlled study, 109 patients suffering from local and vasomotor postmenopausal complaints were randomly assigned to treatment with either depot vaginal suppositories containing 3.5 mg oestriol (E3) or a placebo. The treatment schedule comprised one vaginal suppository twice weekly for 3 weeks initially, followed by maintenance therapy with one vaginal suppository weekly for the 6-month study period. The effectiveness of the therapy was assessed on the basis of questionnaires (Kupperman index for vasomotor complaints and an original urogenital index for local complaints) and gynaecological examinations which included assessments of vaginal cytology, vaginal pH and Doderlein bacilli. To rule out induced endometrial proliferation, endometrial biopsies were performed in 50 women before and after the study. The vaginal depot (E3) formulation showed highly significant superiority over the placebo with respect to therapeutic effect on local urogenital complaints and alleviation of vasomotor complaints, including hot flushes. Analysis of the endometrial biopsies indicated that the monotherapy used caused no endometrial stimulation. Taking into account the minimal rate of adverse effects, the 3.5 mg E3 depot formulation studied represents a useful variant in the range of preparations available for the treatment of post-menopausal complaints. PMID- 1921740 TI - Binding properties of monoclonal antibodies to rabies virus. AB - The monoclonal antibodies (mAbs) obtained by immunizing mice with a tetradecapeptide corresponding to the 190-203 region of rabies virus glycoprotein, involved in binding to the acetylcholine receptor (AchR), displayed different specificities to different rabies virus strains. These mAbs, when used in immunofluorescence tests, allowed differentiation of wild rabies viruses from the attenuated ones. PMID- 1921741 TI - Protection tests in pigs vaccinated with the lapinized Chinese strain of hog cholera virus (HCV) previously adapted in a minipig kidney (MPK) cell line, to challenge infection with virulent HCV. AB - Pigs which had been vaccinated with the Lapinized Chinese strain of Hog Cholera Virus previously adapted in a minipig cell line cultures (MPK-LC-HCV), resultet to be protected when they were subjected to challenge infection with virulent Hog Cholera Virus (HCV) 6 or 11 months later. The challenge virus was never isolated from any of the vaccinated pigs. The MPK-LC-HCV vaccine induced a significant rise of the antibody titer to the HCV in pigs kept under field conditions. PMID- 1921742 TI - Reemergence of Shigella dysenteriae type 2 in Sicily: an epidemiological evaluation. AB - Three strains of Shigella dysenteriae type 2 were isolated from a small household outbreak which occurred in Palermo, Sicily, during summer 1990. Two isolates were recovered from hospitalized patients and one from an asymptomatic carrier. The infection could not be associated with travel to foreign countries or contact with travellers returned from abroad. Since 1953 S. dysenteriae has been never isolated in Southern Italy. The isolates from dysentery cases were susceptible to antibiotics and carried a plasmid of 120 MDa associated with a small cryptic plasmid; in contrast, the strain isolated from the healthy carrier contained an additional plasmid of approximately 40 MDa, which codified for resistance to ampicillin, streptomycin, sulfamethoxazole and trimethoprim. All strains showed some atypical biochemical properties, but their rRNA-DNA patterns of hybridization were closely similar to that of the reference strains of type 2 and easily distinguishable from those of the other types of non-Shiga bacillus reference strains. Epidemiological isolation features of these strains suggest a possible circulation of this Shigella species in Sicily. Genetic characterization of these strains may be useful for surveillance of infections by this organism. PMID- 1921743 TI - Streptococcus mutans: classification in bacteriocin-types. AB - A sample of S. mutans bacteriocins was studied to obtain a useful outline of strain typing since their synthesis has proved stable and not under plasmidial control. The inhibiting effectiveness against 9 oral streptococci and the sensitivity of mutacins produced by 49 S. mutans strains to heat, chloroform and proteasic activity were evaluated. On the basis of our results the producing strains are classified into five different types. We examine the possibility of obtaining a useful typing with bacteriocins and we discuss the choice of the most suitable number of indicators to arrange the strains in a limited cluster number for epidemiological purpose, or to classify freshly isolated S. mutans strains into bacteriocin-types. PMID- 1921744 TI - Prevalence of Toxoplasma gondii antibodies among children and teenagers in Italy. AB - Between 1987 and 1989, the prevalence of antibodies to Toxoplasma gondii was determined by ELISA in serum samples from 1,494 apparently healthy subjects, 3-18 years old. Subjects were selected by a systematic cluster sampling from five geographical areas in Italy. The overall prevalence of antibodies was 17.9%, increasing from 4.7% in 4-6 year olds to 28.4% in 17-18 year olds (P less than 0.01). A slight predominance was observed among males (18.2% vs. 17.5% in females), as well as among subjects residing in Southern Italy and the Islands (21.9% vs. 19.2% in subjects residing in the North), but neither difference was statistically significant. Toxoplasma infection was associated with sociodemographic factors. Subjects belonging to a household with six or more persons had a 1.8-fold risk (C.I. 95% = 1.3-2.6) and subjects whose fathers had less than six years of schooling had a 2.7-fold rosk (C.I. 95% = 1.8-3.9) of previous exposure to toxoplasma infection. Considering the large proportion (70%) of young women entering childbearing age without toxoplasma antibodies, it appears that the risk of congenital toxoplasmosis will not be negligible in Italy in forthcoming years. PMID- 1921745 TI - Characterization of Newcastle disease viruses isolated from pigeons in Italy. AB - The authors report the results of characterization studies of three strains of Newcastle disease virus (NDV) (two isolated from pigeons and one from chickens). The plaque cloning of the viruses, showed that each NDV strain consists of different clones of genetically mixed viral populations. The pigeon NDV isolates were classified as lentogenic using mean death time (MDT) determination; while the intracerebral pathogenicity index (ICPI) was the same as the velogenic NDV strain. PMID- 1921746 TI - Borreliosis risk after tick bite in north-eastern Italy. AB - Lyme Borreliosis is an infectious disease caused by the Borrelia burgdorferi spirochete transmitted to man by a tick bite. The aim of this study was to assess the predictive value of tick bites for the diagnosis of Borreliosis in a sample of 266 subjects residing in an endemic area of north-eastern Italy. In the serological diagnosis of Borreliosis, positive and negative predictive values of tick bites were found to be 24% and 88% respectively. PMID- 1921747 TI - Preliminary evaluation of sensititre system for identifying gram-negative bacilli. AB - The automated microdilution Sensititre System (Sensititre, LtD.) was evaluated for the identification of 120 clinically isolated fermenter and non-fermenter Gram negative bacilli and of 12 ATCC reference strains (American Type Culture Collection). Daily and overnight (5 and 18 hours) identifications were performed according to the manufacturer. In both cases, the results were compared with those obtained with the overnight API 20E (API System, La Balme les Grottes, Montalieu Vercieu) used as reference method. Concordance between the results obtained after 5 hrs of incubation and those obtained with API 20E was found in 65% of cases (acceptable identification criteria with probability over 80%). When results were determined after 18 hrs of incubation (identification criteria with probably over 80%) concordance was found in 82.5%. Reproducibility obtained by repeated (10 times) identification with four different strains was 100% both at 5 hrs and 18 hrs. Identification accuracy of the 12 ATCC strains was 8/12 (66.6%) after 5 hrs and 12/12 (100%) after 18 hrs. PMID- 1921748 TI - Sexually transmitted diseases: advances in diagnostic biotechnologies. A brief overview. PMID- 1921749 TI - Protection against Candida albicans gastrointestinal colonization and dissemination by saccharides in experimental animals. AB - Pre- or post-treatment of duodenal discs with mannose, N-acetylglucosamine or chitin soluble extracts (CSE) prevented the adherence of Candida albicans to gastrointestinal tract. CSE was the most effective in blocking the adherence of C. albicans. Treatment of infant mice with saccharides significantly reduced the systemic spread of C. albicans inoculated into the gut. The best protection was obtained when the saccharides were given 2 days prior to the infection and continued over the course of the infection. However, systemic spread was reduced with a single dose of saccharide 30 min before infection. The saccharides may bind to the gastrointestinal mucosa and block the attachment of C. albicans. PMID- 1921750 TI - Porous phase model of the lung interstitial fluid motion. AB - A mathematical model of nonsteady-state fluid movement in the lung interstitium during hydrodynamic loading is evaluated. The model is based on experimental results obtained in isolated perfused canine lungs. The interstitium is treated as a porous phase with an elastic framework, able to relax; all resistance to flux is in the interstitial tissue and not in the endothelium. A numerical iteration procedure was applied for the calculation of fluid transfer coefficients. The model describes space distribution of driving pressures in the interstitium. PMID- 1921751 TI - Demonstration of actin filament stress fibers in microvascular endothelial cells in situ. AB - We have developed a method for immunostaining the microvascular tree of rat mesenteric windows in situ. The procedure consists of three steps, i.e., mild fixation with formaldehyde, controlled proteolytic digestion of the mesothelial layer, and permeabilization with acetone. Discrimination between different microvascular segments was possible by double-fluorescent staining with antibodies to the smooth muscle isoform of alpha-actin and to nonmuscle myosin from platelets. Antibodies to nonmuscle myosin labeled numerous longitudinally oriented cables in endothelial cells of all microvascular segments (arterioles, metarterioles, pre-, mid-, and postcapillaries, small venules). Occasionally, the myosin-containing cables displayed the interrupted sarcomere-like staining pattern that is diagnostic for stress fibers. In contrast, staining of actin filaments with phalloidin-rhodamin resulted in a noninterrupted, continuous fluorescence of the stress fibers. A possible functional role of microvascular endothelial stress fibers is to serve as a tensile cytoskeletal scaffold that stabilizes the tubular, three-dimensional geometry of microvessels and, in addition, to help the endothelium resist the shear forces created by blood flow and by collision with red and white blood cells. PMID- 1921752 TI - A theory for fluid transport through interstitial connective tissue. PMID- 1921753 TI - A three-dimensional analysis of plasma skimming at microvascular bifurcations. AB - This paper analyzes an important underlying mechanism for the discharge hematocrit reduction observed in microvessels, which refers to the plasma skimming from the cell-free layer near the parent tube wall in the presence of a side branch. The three-dimensional theory recently developed by the authors (Yan et al., 1991, J. Fluid Mech., in press) for treating the simple shear flow past a side branch tube in a plane wall with suction is first summarized and then extended to treat T bifurcations from parent vessels with an upstream Poiseuille flow. For unequal vessel bifurcations, a fundamental new dimensionless group, Q = 1/8(qb/qp)(Rp/Rb)3, is derived whose value determines the shape of the upstream capture tube of the plasma phase, when the partitioning qb/qp of the flow into the side branch and the ratio Rp/Rb of the radii of the parent and side branch vessels are varied. Closed form expressions are then presented for the three dimensional fluid capture tube shape upstream of the bifurcation which are valid when Q greater than 1 or Q less than 0.2. Based on this theory and its modification for an upstream Poiseuille velocity profile, the separating surface shape, the critical minimum fractional flux for incipient cell capture, and the discharge hematocrit defect and its dependence on the flow rate are predicted. It is shown, furthermore, that for flows typical of the microcirculation, a single dimensionless number, P = 3 pi Q(Rb/gamma 2), with gamma being the cell-free layer thickness, can be defined whose value determines the discharge hematocrit defect that arises from plasma skimming. The minimum critical flow rate for any red cells to enter the side branch is then given by the criterion P = 1. Although this theory does not account for the cell screening effect arising from the hydrodynamic interaction between the cells and the tube walls, it leads to predictions which exhibit the same trends as the experimental observations and is able to explain the results of several seemingly contradictory microvascular experiments that have puzzled investigators in recent years. PMID- 1921754 TI - Effects of temperature on cutaneous microcirculation in vibration syndrome. AB - In order to clarify the role of cold on the cutaneous microcirculation in vibration syndrome, groups of rabbits vibrated at 4 degrees and room temperature served as the subjects of this study. A cold provocation test, capillary microscopy, and laser-Doppler flowmetry were used to evaluate the microcirculations of the test rabbits. The results indicated that vibration induced impairment of the microcirculation was more prominent in the 4 degrees vibration group than in the room temperature group. The severities of the microcirculatory disturbances were dose-effect correlated. Vibration induced not only functional disturbances but also structural destruction of the capillaries. Furthermore cold temperatures enhanced these abnormalities of the blood vessels. PMID- 1921755 TI - The high splenic hematocrit: a rheological consequence of red cell flow through the reticular meshwork. AB - The spleen concentrates blood to twice arterial hematocrit, but how it does so is poorly understood. We hypothesize that hemoconcentration results from percolation of blood through the reticular meshwork (RM) between capillary endings and venous channels. The RM has a large flow cross section, producing low shear rates, and an enormous surface area for red blood cell (RBC) adhesion. If these conditions cause slowing of RBCs with respect to plasma, increased hematocrits will occur (inverse Fahraeus effect). Movements of individual RBCs through the RM were studied from intravital microscopic videorecordings of Ringer-perfused mouse spleens. Analysis of three 70-microns paths showed characteristic "stop and go" motion, RBCs spending 0.015 to 9.71 see in any 7-microns segment, despite steady (+/- 15%) perfusate velocity. At some locations RBCs adhered to reticular cells/fibers by point attachment and at others they became caught over fibers. In general, RBCs were detained in the RM by surface interactions rather than by narrow channel. Perfusate ("plasma") velocity was estimated to be at least that of the fastest RBCs in each segment. Ratios of overall mean RBC and plasma velocities for three paths were 0.19, 0.20, and 0.37. Applying these velocity ratios to a feed hematocrit of 40% leads to predicted splenic hematocrits up to 78%. We conclude that this slowing of RBCs within the reticular meshwork provides the primary mechanism for generating the high intrasplenic hematocrit. PMID- 1921756 TI - Vascular smooth muscle structure and juvenile growth in rat intestinal venules. AB - The morphological structure of individual vascular smooth muscle cells from intestinal venules was evaluated with a combination of quantitative scanning (SEM) and transmission (TEM) electron microscopy techniques. In addition, growth of individual venular smooth muscle cells and of the overall vessel wall was compared from measurements of these variables during the rapid juvenile growth spurt from ages 4 to 6 and 10 to 12 weeks in Wistar-Kyoto rats. SEM revealed that smooth muscle cells of intestinal venules in weanling rats are very long (379 +/- 91 [SD] microns) and wide (6.0 +/- 1.3 microns) and very little further cell enlargement occurs during rapid juvenile growth. TEM studies indicated that passive inner vessel diameter and total muscle layer cross-sectional area of both the largest and intermediate diameter venules of young rats, as well as the percentage of the total wall area as muscle tissue in each venule type, did not significantly increase during body growth. These observations indicate that both the intestinal venules and their smooth muscle cells reach mature dimensions at a very early stage of life. Comparison of intestinal vascular smooth muscle cell dimensions indicates that venular smooth muscle cells are much larger in both cell length and volume than comparable arteriolar smooth muscle cells. PMID- 1921757 TI - Serum albumin decreases transendothelial permeability to macromolecules. AB - We examined the effects of serum albumin and other serum proteins on the fluxes of tracer 125I-albumin (MW 69 kDa) and 125I-haptoglobin (MW 100 kDa) across the pulmonary artery endothelial monolayer in vitro to test the role of serum proteins in modulating the endothelial barrier function. Replacement of control complete culture medium (20% fetal calf serum in DMEM) with DMEM alone increased the transendothelial 125I-albumin clearance rate (a measure of 125I-albumin permeability) by 83% of the control value. Repletion with 50% calf serum or with 2.0 g% albumin (i.e., the albumin concentration in 50% serum) decreased 125I albumin permeability to the control value. This effect of serum or albumin was concentration-dependent since neither 12.5% serum nor 0.5 g% albumin (i.e., albumin concentration in 12.5% serum) altered 125I-albumin permeability from control values. The ammonium sulfate-precipitated serum protein fraction rich in albumin decreased 125I-albumin permeability from the control DMEM value, whereas serum fractions containing predominantly gamma-globulin or depleted of protein did not significantly alter 125I-albumin permeability. Other serum proteins that have been proposed to reduce endothelial permeability, alpha 1-acid glycoprotein (0.035-0.14 g/100 ml) and fibronectin (5 mg/100 ml), did not decrease 125I albumin permeability from DMEM values. The endothelial permeability of 125I haptoglobin of 4.63 +/- 0.53 x 10(-6) cm/sec in the presence of DMEM was 30% of the 125I-albumin permeability value. The addition of 2.0 g% albumin or 50% serum decreased 125I-haptoglobin permeability to 57 and 31%, respectively, of the DMEM value. These results indicate the critical role of serum albumin in regulating the restrictiveness of the endothelial barrier to macromolecules. PMID- 1921758 TI - Characterization of two bacteriocins produced by Clostridium perfringens. AB - Two types of bacteriocins were shown to be produced in succession by a strain of Clostridium perfringens SN-17. They were separated by diethylaminoethyl cellulose (DEAE) column chromatography at pH 8.5 with a linear concentration gradient of NaCl. One type of bacteriocin (named SN-a) was eluted at 0.07 M and the other type (named SN-b) was at 0.12 M. Each of these was partially purified in a series of column chromatographies: DEAE, Sephadex G-200 (or Bio Gel P-150), and hydroxyapatite. Specific activities of SN-a and SN-b after the last chromatography were at most 30- to 50-fold that of culture filtrate of the organisms. Chromatographed SN-a migrated as a single zone in polyacrylamide gel electrophoresis (PAGE) and the zone showed high biological activity. On the other hand, PAGE pattern of SN-b revealed the presence of a few contamination materials. The activity of SN-b after the last chromatography was hardly recovered from the gel but inactivated SN-b was identified in the gel by examining bacteriocin activity of the DEAE fractions recovered from the gel. The molecular weight of the SN-a and SN-b was determined to be about 70,000 and 100,000, respectively, by molecular sieve chromatography. These bacteriocins were very sensitive to protease but insensitive to DNase and RNase. Bacteriocins were both completely inactivated at 55 C and they were more stable in alkaline pH than in acidic pH. SN-a and SN-b were adsorbed in different ways on the surface of the producer and insensitive strains. Several differences and similarities between these 2 bacteriocins are discussed with special reference to the relationship between them. PMID- 1921759 TI - Neutralization of Shwartzman-inducing activity by antibodies recognizing the Re core or lipid A structures of lipopolysaccharide from Salmonella minnesota R595 and Pseudomonas vesicularis JCM1477. AB - Antibodies recognizing the Re core or lipid A structures of lipopolysaccharide (LPS) derived from Salmonella minnesota R595 and Pseudomonas vesicularis JCM1477 were tested for the ability to neutralize the preparatory activity of endotoxin using the local Shwartzman reaction. Shwartzman-inducing activity of R595 LPS (Re form) was strongly suppressed when the LPS was incubated with the rabbit anti R595 antiserum or the purified IgG antibody which recognizes core region of the LPS. The antiserum also suppressed the preparatory activity of LPS from S. typhimurium SL1102 (Re) and Escherichia coli F515 (Re), but not that of either S. typhimurium LT-2 (S) LPS or R595 lipid A. Moreover, it was found that the murine monoclonal antibody (MAb), SmRe100G (IgG2a) which recognizes the core region of R595 LPS, significantly suppressed the preparatory activity of R595 LPS. Both conventional antibodies specific to R595 lipid A, which contains a 1,4' bisphosphorylated beta-D-glucosaminyl-alpha-D-glucosamine disaccharide structure, and JCM1477 lipid A, which contains a monophosphorylated 3-amino-D-glucosamine disaccharide structure, neutralized the preparatory activity of homologous and a closely related lipid A, but not that of LPS. In addition, it was observed that MAb Sm5G (IgG2b) specific to enterobacterial lipid A preparations (especially R595 lipid A) neutralized the preparatory activity of R595 lipid A, although the effect was somewhat weak as compared with that of rabbit antiserum. These results suggest that anti-Re LPS antibody binding to the core of Re LPS is involved in suppressing the endotoxic activity of Re LPS, and that the direct binding of anti lipid A antibody to some specific epitopes of lipid A is important in neutralizing the endotoxic activity. PMID- 1921760 TI - Characterization of antibody response to Pseudomonas aeruginosa in patients with wound infections. AB - ELISA was used to measure the amount and avidity of IgG antibodies to exotoxin A (ExA) and 7 Fisher's immunotypes of lipopolysaccharide (LPS) in the sera of 13 patients with mild or moderate Pseudomonas aeruginosa infections. Changes in the specificity of tested sera during the course of infection were demonstrated. A statistically significant increase was seen in the amount and avidity of the antibodies to ExA in a majority of the sera, and an increase was seen in amount of antibodies to LPS immunotype 4 in the sera of patients with moderate infections. PMID- 1921761 TI - A synthetic peptide homologous to retroviral transmembrane envelope proteins depresses protein kinase C mediated lymphocyte proliferation and directly inactivated protein kinase C: a potential mechanism for immunosuppression. AB - CKS-17, an immunosuppressive peptide homologous to certain retroviral transmembrane envelope protein, has been shown to inhibit lymphocyte proliferation in response to mitogens or alloantigens when covalently attached to bovine serum albumin (CKS-17-BSA). To define its site of action, we determined if CKS-17 conjugated to human serum albumin (CKS-17-HSA) could block the direct activation of lymphocytes by phorbol-12-myristate-13-acetate (PMA) or by a synthetic diacylglycerol, dioctanoylglycerol (DiC8). CKS-17-HSA inhibited lymphocyte proliferation in response to PMA and ionomycin in a dose-dependent manner with up to 88% inhibition occurring with 15 microM CKS-17-HSA. The conjugated peptide also inhibited the proliferation of lymphocytes in response to DiC8 and ionomycin by up to 57% at 15 microM CKS-17-HSA. Based on these findings we investigated the effect of CKS-17-HSA on the activity of protein kinase C (PKC), an enzyme directly activated by PMA and DiC8. PKC was isolated chromatographically from the cytosol of human neutrophils or the human lymphoblastoid cell line Jurkat. CKS-17-HSA caused a dose-dependent enzyme inhibition with a concentration giving half-maximal inhibition (IC50) of ca.3 microM and greater than 95% inhibition at 15 microM CKS-17-HSA. Inhibition of PKC by the conjugated peptide was not reversed by increasing concentrations of Ca2+, Mg2+, phosphatidylserine, diolein, or adenosine triphosphate (ATP), indicating that the conjugated peptide did not function as a chelator or competitive inhibitor. In contrast to its effects on PKC, CKS-17-HSA did not inhibit the activity of adenosine 3':5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase (PK-A) nor the calcium and phospholipid-independent form of PKC (PK-M). Moreover the peptide inhibited in vivo PKC activity in cytosol of intact cells and in membrane of PMA-stimulated cells. These results suggest that the inhibition of lymphocyte proliferation by CKS-17-HSA may be due to the direct inactivation of PKC. PMID- 1921762 TI - Colonization of Helicobacter pylori in the gastric mucosa of Mongolian gerbils. AB - Helicobacter pylori was orally inoculated into Mongolian gerbils. The organisms were able to colonize in the gastro-mucosal layer of the gerbils, especially in those gerbils which had mucosal lesions caused by indomethacin treatment. The pathological changes developed by H. pylori infection were restricted to the stomachs, and only slightly inflammatory cells were observed. PMID- 1921763 TI - Effect of Clostridium perfringens alpha toxin on contraction of isolated guinea pig diaphragm. AB - The effect of Clostridium perfringens alpha toxin on contraction induced by electric stimulation of isolated guinea-pig diaphragm was investigated. The toxin inhibited electrically stimulated contraction of the tissue in a dose- and incubation time-dependent manner. Tetrodotoxin resulted in no effect of the action of the toxin. Nifedipine dose-dependently delayed the action of the toxin, but verapamil and diltiazem did not. On the other hand, treatment of the toxin with N-acetylimidazole caused significant reduction of the inhibitory activity of the toxin on contraction, but did not cause significant loss of phospholipase C activity (PN activity) as measured by hydrolysis of p nitrophenylphosphorylcholine. The data showed that the toxin impairs contraction of isolated guinea-pig diaphragm. PMID- 1921764 TI - Human immunodeficiency virus infection in cells of myeloid-monocytic lineage. AB - We established persistent infection with a strain of human immunodeficiency virus type 1, HTLV-IIIB, in a promyelomonocytic cell line, ML-1 (CD4 antigen nearly negative and CD4 mRNA negative), and a promonocytic cell line, THP-1 (CD4 antigen positive). Different reaction of giant cell formation was found after co cultivation of infected and uninfected cells of ML-1, HL-60, THP-1 and U-937 cell lines with uninfected and infected MOLT4 (a T-lymphoma cell line). PMID- 1921765 TI - Jane--the care of a deaf woman. PMID- 1921766 TI - "She'll be all right--she can lip-read". PMID- 1921767 TI - The significance of autocorrelation in fetal monitoring. PMID- 1921768 TI - [Turbidostat culture of yeast during transition from a resting state to active growth]. AB - The age components of a Saccharomyces cerevisiae 14 culture and the kinetics of its growth were studied afer the quiescent state at the onset active growth. The following factors induced the quiescent state: the cessation of a chemostat flow for 24 h, growth inhibition with 2,4-dinitrophenol (DNP) for 24 h, the storage of a culture growing on agar in a refrigerator during 24 h. The process of transition from the point of growth activation to the maximum rate of growth was then studied in turbidostat. This process took the shortest time in a refrigerated culture as well as in a culture that had been limited with a phosphorus source and in a culture limited with a nitrogen source and grown in chemostat at D = 0.26 h-1. The process was longer in cultures that had been either limited with glucose or inhibited with DNP and longest in a chemostat culture limited with a nitrogen source at D = 0.15 and 0.05 h-1. The rate of initial mitosis phases in the yeast is presumed to exert the greatest effect on the duration of this transition process. PMID- 1921769 TI - [Ultrastructural features of Rhodococcus rubropertinctus and Streptococcus lactis dissociants]. AB - Three Rhodococcus rubropertinctus dissociants (R, S and M) and two Streptococcus lactis dissociants (R and S) were compared using the electron microscopy method of negative contrasting. The cell wall of R.rubropertinctus dissociants had a thickness of 40 nm (R), 30 nm (S) and 20 nm (M). The cell wall of S. lactis dissociants was 35-55 nm (R) and 25-30 nm (S) thick. 1.5-2-fold variations in the thickness of cell walls could account for the different resistance of the dissociants against the action of such external factors as dehydration, antibiotics, UV, elevated NaCl concentrations, etc. PMID- 1921770 TI - Is the ingestion of fluoride an immunosuppressive practice? PMID- 1921771 TI - Toward an analysis of conscious activity: 1. Evolution of vigilance. AB - Previous articles (3-6) have presented two experimental methods--the Dynamic Behavioral Stage Analysis Method (DBSAM) and the Micro-sleep and Micro wakefulness Processing Method (MMP)--as investigational approaches oriented in the direction of developing a theoretical concept. MMP employs a simplified method that uses duration of sleep and wakefulness (ti) as the parameter to alter the time units and reverse diagnose sleep and wakefulness as wakefulness and sleep, respectively. Results of vigilance (O) standard diagnosis and those of vigilance (+/- n) standard diagnosis (evaluating apparent sleep and wakefulness based on vigilance (+/- n)) werer compared using model data. This paper discusses the conceptual background necessary to understand the correlation between sleep, wakefulness, and consciousness, using model data. It also hypothesizes that conscious activity level, generated by sleep and wakefulness vectors, acts as an address specifier of information that is input and output within the brain. PMID- 1921772 TI - Is the main problem in free radical damage caused by radiation, oxygen and other toxins the loss of membrane essential fatty acids rather than the accumulation of toxic materials? AB - Ionising radiation, oxygen radicals, cytotoxic drugs, alcohol, inflammation, neuroleptics and many other agents are thought to damage cells in part by promoting the formation of free radicals. These radicals in turn lead to the peroxidation of essential fatty acids (EFAs) and the formation of a wide range of toxic metabolites. The production of toxic radicals and metabolites is thought to be the main cause of the damage. It is suggested that this view may be wrong, with the major component of the toxicity being attributable to loss of the highly unsaturated EFAs from membranes. If this view is correct, then antioxidant and anti-free radical therapy will be inadequate to prevent and reverse such damage. Treatment must include measures to replace the missing EFAs. PMID- 1921773 TI - Anabolic/androgenic steroid abuse and thrombosis: is there a connection? AB - Anabolic/androgenic steroid abuse is an increasing medical and public health problem. The uncontrolled use of these agents has been associated with numerous toxic side-effects including deleterious cardiovascular changes. The most widely reported to these latter changes include the development of adverse lipid profiles and hypertension. Acute thrombosis has only recently been linked to androgen abuse. Such a causative link has been proposed in reports of acute myocardial infarction and stroke in several athletes using androgens. Unfortunately, there exists no direct evidence that androgens are thrombogenic in humans. However, indirect experimental data suggests that androgens affect platelet aggregation, coagulation proteins and the vascular system in ways that facilitate thrombosis. Androgens also increase several anticoagulant and fibrinolytic proteins. However, they have not been shown to protect from thrombosis in high risk patients. Existing data supports a possible thrombogenic effect of exogenous androgens. Further studies are needed to clarify the hemostatic influence associated with androgen abuse in weightlifters. The abuse of these agents may diminish if acute thrombosis becomes clearly and scientifically associated with their uncontrolled use. PMID- 1921774 TI - A unique function for ascorbate. AB - Vitamin C is a reducing substance, an electron donor. When vitamin C donates its two high-energy electrons to scavenge free radicals, much of the resulting dehydroascorbate is re-reduced to vitamin C and therefore used repeatedly. Conventional wisdom is correct in that only small amounts of vitamin C are necessary for this function because of its repeated use. The point missed is that the limiting part in nonenzymatic free radical scavenging is the rate at which extra high-energy electrons are provided through NADH to re-reduce the vitamin C and other free radical scavengers. When ill, free radicals are formed at a rate faster than the high-energy electrons are made available. Doses of vitamin C as large as 1-10 g per 24 h do only limited good. However, when ascorbate is used in massive amounts, such as 30-200+ g per 24 h, these amounts directly provide the electrons necessary to quench the free radicals of almost any inflammation. Additionally, in high concentrations ascorbate reduces NAD(P)H and therefore can provide the high-energy electrons necessary to reduce the molecular oxygen used in the respiratory burst of phagocytes. In these functions, the ascorbate part is mostly wasted but the necessary high-energy electrons are provided in large amounts. PMID- 1921775 TI - Unitary model of cell activation, growth control, cancer and other diseases: 1. Activated oxygen species and arachidonic acid modulation of solute permeabilities, internal Ca, Na and AOS levels and DNA transcription and synthesis. AB - A comprehensive model of cellular activation and proliferation is developed. The model has arachidonic acid (ARA) produced mainly from PLA2 on both sides of the membrane, and superoxide and other activated oxygen species (AOS) formed from O2 by electrons passing out through membrane NANPH and NADH oxidases, as the immediate stimulants of solute permeability. Both ARA and AOS interact with the various solute channel proteins especially their external thiols and disulfides, to increase influx of metabolic substrates, Na, Ca and O2. PLA2 and NADPH oxidase are turned on by growth factors at their receptors acting through tyrosine kinase phosphorylations of messenger proteins GP and ras p-21, stimulated proteases, and by Ca-calmodulin. The adenylate cyclase system has opposite, deactivating character as it increases efflux of Ca and desensitizes growth factor receptors by phosphorylation to shut down the increased solute permeability. Most cancer types are due to carcinogen binding to cell membrane channel and mitochondrial sites for increased solute influx with excessive AOS production inside the cell from mitochondria and other vesicles. High Ca, Na and AOS stimulate proliferation with extra high levels causing transformation to the autogenic, more embryonic type cancer cell. PMID- 1921776 TI - The age incidence of childhood acute lymphoblastic leukaemia. AB - A mathematical model of childhood acute lymphoblastic leukaemia (ALL) is presented which is based on the assumptions that: 1) malignant clones of lymphoblasts arise by spontaneous mutation; 2) this is normally prevented by repair systems which either cause intracellular DNA repair or eliminate the malignant clone; and 3) the repair systems are fallible and their performance decays at random with time. If the major drive to lymphocyte division is microbial antigens then the model produces a reasonable fit to published data on the age distribution of ALL. Furthermore the model offers an explanation for the apparent increase in the incidence of ALL which is associated with improved social conditions. PMID- 1921777 TI - On the handedness of the scaffolds of sister chromatids. AB - We discuss a mechanical model for the mirror-symmetric inversion of the scaffold's helicity of replicated chromatids vis-a-vis that of their templates. The paper ends with comments on the orientability of certain genes and on the effects of such topologies upon (a)symmetric gene expression, in general. Our model and its generalizations apply only to the special subclass of 'coiled' chromatids whose statistical distribution in the genome of normal and of malignant cells is not known precisely. PMID- 1921778 TI - Gregg's rubella legacy 1941-1991. PMID- 1921779 TI - Warning: death statistics can be a health hazard. PMID- 1921780 TI - Variations in practice patterns. PMID- 1921781 TI - Post polio syndrome: what can we do? PMID- 1921782 TI - Influenza A(H1N1): a widening spectrum? AB - OBJECTIVE: To study the incidence of H1N1 influenza from 1977 to 1988 in unvaccinated volunteers and the effects of continuing minor antigenic change (antigenic drift) in the virus. DESIGN: Prospective study by a group of general practitioners, backed up by virological findings. PARTICIPANTS: Mainly patients of the general practitioner group, also some doctors and members of staff. There were 287 participants during 1977-1981, and 207 at the end of 1988. INTERVENTION: Any participant deemed to be "at risk" was encouraged to be vaccinated and to withdraw from the study. BACKGROUND: In 1957, H1N1 subtype influenza had been displaced by H2N2 (Asian) subtype. In 1968, H2N2 was displaced by H3N2 (Hong Kong) subtype. During 1977, H1N1 influenza unexpectedly reappeared in Asia, and spread widely. The resurgent strain, designated A/USSR/90/77(H1N1), caused world pandemics, attacking (almost exclusively) persons who had been born since the 1950-1951 northern winter and causing negligible mortality. It did not displace the current H3N2 strain, and strains of both subtypes have continued to emerge independently. HYPOTHESIS: Antigens of A/USSR resembled closely those of the 1950 1951 H1N1 strain, which apparently was rendered antigenically inert between 1951 and 1976 (possibly frozen) and was reactivated during 1977. Antigenic drift was then resumed. MAIN OUTCOME MEASURE: The A/USSR/90/77 strain and its close successor, A/Brazil/11/78, attacked mainly the young, whose previous exposure to H1N1 antigens had been minimal or zero. Mortality during the A/USSR pandemics was negligible because death from influenza in people aged less than 30 years is rare. Would continuing antigenic drift ultimately widen the H1N1 spectrum of attack? RESULT: During the epidemic of 1988, A/Taiwan/1/86(H1N1) attacked a wider range of age groups than had A/USSR or A/Brazil. CONCLUSION: Assuming that H1N1 viruses continue to undergo further antigenic drift, an ever widening age spectrum of H1N1 attack may be expected. PMID- 1921783 TI - Finger injuries to children involving exercise bicycles. AB - OBJECTIVE: A previously unreported source of injuries to children, the exercise bicycle, is identified and the associated injuries and their treatment are described. DESIGN: A retrospective review of clinical records and the records of the Victorian Injury Surveillance System. SETTING: The Plastic Surgery Unit of the Royal Children's Hospital, Parkville, Victoria. PATIENTS: Seventeen children with finger injuries from exercise bicycles presented to the Emergency Department of the hospital and one presented to one of us (K L M) at his private practice. Sixteen of the 18 children were under five years of age; 10 were less than two years of age. Five times as many boys as girls were injured. INTERVENTIONS: Fourteen children required surgical treatment of their injuries. RESULTS: Four children had superficial injuries not in need of surgical repair. Eleven children had single digit injuries--five had injuries that were repaired by suture; five had complete avulsion of the tip of the digit that required flap graft repair; and one child underwent amputation of the index finger. Three boys had multiple digit injuries, each one requiring the amputation of a digit and repair of other digits. Two of these boys underwent replantation of a digit; only one replantation was successful. CONCLUSIONS: The most dangerous parts of the exercise bike were the wheel, the chain and the sprocketwheel. Design modifications and education of parents about the risks for children playing near exercise bikes are warranted. PMID- 1921784 TI - Sublingual apomorphine solution in Parkinson's disease. AB - OBJECTIVE: To compare the effects of single doses of oral levodopa, subcutaneous apomorphine and sublingual apomorphine. DESIGN: Single-blind placebo-controlled comparative study. SETTING: Subjects were admitted as day patients to the neurology ward. PATIENTS: Five patients with idiopathic Parkinson's disease and "end of dose deterioration" entered and completed the study. INTERVENTIONS: Patients were given domperidone (20 mg by mouth three times a day) to prevent nausea and apomorphine (1-3 mg by subcutaneous injection), apomorphine in glycerol (10-30 mg sublingually) or their usual levodopa regimen. MAIN OUTCOME MEASURES: Efficacy, time to onset of effect and duration of effect of oral levodopa, subcutaneous apomorphine and sublingual apomorphine. Tremor amplitude and timed pegboard and gait tasks were used as objective indices of clinical state. RESULTS: Maximal efficacy of the three treatments was comparable (P = 0.28 0.99). Mean latency to onset of effect of both formulations of apomorphine was less than that of levodopa (P = 0.022-0.048) but so was the duration of effect (P = 0.044-0.049). CONCLUSIONS: Sublingual apomorphine may be a convenient means of rapidly terminating "off" periods associated with long term levodopa therapy. PMID- 1921785 TI - Letters to go: general practitioners' referral letters to an accident and emergency department. AB - OBJECTIVE: To investigate the content of general practitioners' referral letters to the Accident and Emergency (A&E) Department of a large regional hospital. METHOD: Two hundred and fourteen consecutive identifiable letters from general practitioners presented by patients over a four week period were reviewed. The accuracy and content of the letters was measured by the presence of 10 key items, and checked against the A&E notes when necessary. A further nine items were examined to discover whether the context of the referral had any influence on letter content. RESULTS: Information that was relatively poorly represented in the letters included social and personal background details, vital signs, regional examination findings, a management plan, and investigation results. The presence in the letter of a management plan or a clear presenting problem was found to be significantly associated with appropriate referrals. CONCLUSIONS: Poor referral letters may reflect a professional distance between the general practitioner and A&E staff that is stretched by the anonymity of the relationship, increasing A&E specialisation, or lack of feedback to the general practitioner. Specific information standards for A&E referrals should be developed to ease contact and to establish criteria for referral. PMID- 1921786 TI - Entry of human immunodeficiency virus infection into a population of injecting drug users, Victoria, 1990. AB - OBJECTIVE: To investigate the pathway by which the human immunodeficiency virus (HIV) is entering populations of injecting drug users (IDUs) in Victoria. DESIGN: A retrospective case-control study comparing the prevalence of self reported risk behaviour in HIV-infected and uninfected Victorian IDUs. SETTING: Subjects were recruited by trained peer outreach workers from their personal networks, community agencies and Fairfield Hospital outpatients, and by a research worker from the major metropolitan prison. PARTICIPANTS: People who had been resident in Victoria for the past 12 months and had injected an illicit drug more than once in the previous three years were eligible to participate. Sixty-two such people (28 HIV-infected, 34 not infected) were included in the study. MAIN OUTCOME MEASURES: The two main hypothesised portals of entry were from the non-IDU homosexual population in Victoria, and from HIV-infected IDUs elsewhere. RESULTS: male homosexual contact was the most consistent risk factor identified by this study (odds ratio [OR], 6.2; 95% confidence interval [CI], 1.7-23.8). Having lived in or visited Sydney before 1986 was also associated with being infected with HIV (OR, 13.2; 95% CI, 1.5-603), and this was associated with homosexuality. Infected IDUs reported more sharing of injecting equipment than controls (OR, 9.0; 95% CI, 1.5-92.5), particularly with sexual partners; when this was the case, they were more likely to always use the injecting equipment after their partner (61% of cases, 0% of controls; OR, greater than or equal to 4.1; P = 0.0006). CONCLUSION: Men who have a history of both homosexual contact and injecting drug use represent the group of IDUs at highest risk of HIV infection in Victoria. Although heterosexual and homosexual IDUs may have limited contact only, a larger epidemic of HIV infection in heterosexual IDUs could spread from homosexual IDUs through the sharing of injecting equipment. PMID- 1921787 TI - Current management of lower genital tract preneoplasia. PMID- 1921788 TI - Students, patients and videotapes. PMID- 1921789 TI - The late effects of polio. PMID- 1921790 TI - Can short hospital admissions be avoided? A review of admissions of less than 24 hours' duration in a paediatric teaching hospital. AB - OBJECTIVE: To review the records of children admitted to hospital for less than 24 hours to assess the appropriateness of the admission and subsequent discharge, and the suitability of these patients for admission to a short stay area rather than the hospital wards. DESIGN: Retrospective study consisting of a one in three sample of all children admitted to the hospital's general medical units over one year. All admissions were listed sequentially, and every third patient was included in the study. SETTING: Royal Children's Hospital, Melbourne; a tertiary paediatric hospital with a major primary care role. PARTICIPANTS: There were a total of 660 patients eligible for inclusion in the study; 220 were selected, and all records were reviewed. RESULTS: It was found that although 87.7% of admissions could be justified on medical grounds alone, the children quickly recovered with at least 65% being fit for discharge within 12 hours of admission. In spite of this the mean duration of admission was 17.0 hours. The majority of patients were suffering from easily diagnosed and treated disorders, with 78.9% falling into four diagnostic groups (asthma, ingestions, infections, and convulsions). Criteria for admission to a short stay observation area were satisfied in 65% of patients (at the time of the study no such area existed in the hospital). No patients were discharged inappropriately early. CONCLUSIONS: A significant number of children require brief hospitalisation for relatively minor illness, but unnecessary delays caused by administrative aspects of hospital admission and relatively infrequent inpatient review by medical staff often lengthen the period of admission. Significant cost savings are possible with the use of a short stay facility, and a large number of patients are suitable for this form of care. PMID- 1921791 TI - Health of Kimberley aboriginal mothers and their infants and young children. PMID- 1921792 TI - AIDS vaccines. PMID- 1921793 TI - Lead: subtle forms and new modes of poisoning. PMID- 1921794 TI - Profiles of antibacterial drug use in Australia and trends from 1987 to 1989. A report from the Drug Utilization Subcommittee of the Pharmaceutical Benefits Advisory Committee. AB - OBJECTIVE: To survey the use by Australian pensioners of orally administered antimicrobial agents supplied through the Pharmaceutical Benefits Scheme over the years 1987-1989. DATA SOURCES: Australian Pharmaceutical Benefits Scheme pensioner data for 1987-1989 and market research data from a private company. DATA EXTRACTION: The data were initially available as the number of prescriptions dispensed and were aggregated on a quarter year basis. These were converted to defined daily doses (DDDs) per 1000 pensioners per day (DDD/1000 per day). This conversion of the data allows comparisons across drug groups, and with prescribing patterns in other countries. The DDD/1000 per day also gives an indication of the proportion of individuals in the community receiving a drug at a particular time. DATA SYNTHESIS: There was a 26% increase in antibacterial drug use over this period. Comparison of prescribing profiles for particular indications with peer consensus guidelines revealed marked discrepancies, particularly for upper respiratory tract infections, urinary tract infections, otitis media and sinusitis. Upper respiratory tract infections accounted for 31% of instances of antibiotic prescribing. Dispensing of amoxycillin/potassium clavulanate relative to amoxycillin as a single agent, showed a marked increase in 1989 to the point where it represented 25% of all amoxycillin used. This could be considered excessive given the lack of evidence that amoxycillin resistance has substantially increased in infections presenting to general practice. The data presented here confirm previous suggestions that Australian antibiotic prescribing is heavily concentrated on the use of broad spectrum agents. By comparison with Norway or Sweden, there is a greater relative use of broad spectrum penicillins and tetracyclines and a lower relative use of phenoxymethylpenicillin and trimethoprim. CONCLUSIONS: Antibiotic prescribing practices in Australia continue to be often inappropriate and expensive, being directed too heavily towards the use of broad spectrum agents and newer more expensive drugs. Correction of such antibacterial drug use will require coordination of educational and regulatory activities that are sensitive to the context of general practice. PMID- 1921795 TI - Isolation of Legionella maceachernii from an immunocompromised patient with severe underlying lung disease. AB - OBJECTIVE: To present the first case in Australia in which Legionella maceachernii has been documented as a cause of infection. CLINICAL FEATURES: A 71 year-old retired carpenter with underlying autoimmune disease and pulmonary fibrosis was admitted to hospital with increasing shortness of breath and fever, and pneumonia was diagnosed. INTERVENTION AND OUTCOME: He was treated with ampicillin then gentamicin and flucloxacillin and later imipenem but his condition deteriorated with progression of the pneumonia and abscess formation and he died 25 days after admission. Subsequently, L. maceachernii was isolated from three sputum samples collected before the patient died. CONCLUSION: There is a need for clinical awareness of the value of sputum culture in the diagnosis of infection due to Legionella spp. other than L. pneumophila. PMID- 1921796 TI - Neuroleptic malignant syndrome in children. AB - OBJECTIVES: To report a case of neuroleptic malignant syndrome (NMS) in a child, and review reports of 11 other paediatric cases of NMS. CLINICAL FEATURES: A 6 year-old child treated with thioridazine for behavioural disturbance developed NMS following an episode of dehydration. The clinical features of this case are compared to other reports of NMS in childhood, and in adults, where the disease is far more common, usually being precipitated by major tranquillisers. INTERVENTION AND OUTCOME: The patient made a full recovery with supportive management. In adults the disease has a mortality of 15%-40%, and two of the previously reported paediatric cases have also been fatal. Treatment options, including dantrolene and antiparkinsonian agents are reviewed. CONCLUSION: NMS is rare in childhood, but is usually precipitated by commonly prescribed drugs. There is a significant mortality associated with the condition, and early diagnosis and treatment are essential for a good outcome. PMID- 1921797 TI - Alcohol and drugs in the workplace: reducing the costs. PMID- 1921798 TI - Let ethics committees authorise new drugs for treatment. PMID- 1921799 TI - Depo-Medrol and myelographic arachnoiditis. PMID- 1921800 TI - Hypernatraemic dehydration after Lucozade. PMID- 1921801 TI - Our nursing homes. PMID- 1921802 TI - Vega testing in the diagnosis of allergic conditions. PMID- 1921803 TI - The physician as patient. PMID- 1921804 TI - Acute respiratory illness in Adelaide children--the influence of child care. PMID- 1921805 TI - Helmets for motorcyclists. PMID- 1921806 TI - Drug availability revisited: a question of balance. PMID- 1921807 TI - Low-dose methotrexate therapy and hepatotoxicity. The view of the hepatologist. PMID- 1921808 TI - The Utstein guidelines. PMID- 1921809 TI - Prevention may be better than cure--but has it worked? PMID- 1921810 TI - Consensus development and the management of hyperlipidaemia in Australia. PMID- 1921811 TI - Treatment of primary hypercholesterolaemia with simvastatin. New Zealand multicentre evaluation. AB - OBJECTIVE: To assess the efficacy of simvastatin in a large patient cohort. DESIGN: In an open multicentre study, after a four week placebo phase, patients were treated with simvastatin for 24 weeks; a subgroup continued therapy for a further 24 weeks. Efficacy of simvastatin (a) with prolonged use over three years, and (b) in combination with bezafibrate was assessed in an open single site study. SETTING: Lipid or cardiology specialist hospital outpatient clinics. PATIENTS: For the open multicentre study, 228 patients with primary hypercholesterolaemia (total cholesterol level greater than 6.5 mmol/L) were recruited, of whom 224 met entry criteria and completed the study. Forty-seven of these patients continued therapy for one year. In the open single site study, 22 patients (with low density lipoprotein [LDL] cholesterol levels greater than 4.3 mmol/L) participated in studies of long term use (n = 9) or of combined therapy (n = 13). INTERVENTION: Therapy in the open multicentre study began with 10 mg of simvastatin per day, doubling to 20 mg after six weeks and then 40 mg after 12 weeks of therapy if total cholesterol levels persisted above 5.2 mmol/L. In the study of long term use, simvastatin (40 mg daily) was taken continuously over three years. In the study of combination therapy, bezafibrate (600 mg daily) was taken in addition to simvastatin (40 mg daily) for 10 months. MAIN OUTCOME MEASURES: Plasma lipid and lipoprotein concentrations. RESULTS: In the multicentre study, total plasma cholesterol levels were reduced by 32.8% from 9.11 +/- 1.84 (in mmol/L, mean +/- SD) to 6.12 +/- 1.25 (P less than 0.001), and LDL cholesterol levels by 41.4% from 6.90 +/- 1.92 to 4.04 +/- 0.31 (P less than 0.001). The effect of therapy was sustained in those patients continuing therapy to 48 weeks. The study of long term use found no significant attenuation of effect over three years of monotherapy. Combined simvastatin/bezafibrate therapy reduced the LDL cholesterol concentration by a further 19.9% (P less than 0.001) from levels achieved on simvastatin alone. CONCLUSIONS: Simvastatin is an effective, well tolerated lipid lowering drug, without significant attenuation of effect with prolonged use. Simvastatin plus bezafibrate appears to be a potentially useful drug combination. PMID- 1921812 TI - Mortality from coronary heart disease and incidence of acute myocardial infarction in Auckland, Newcastle and Perth. AB - OBJECTIVE: To confirm the existence of regional differences in coronary death rates in Australia and New Zealand and to determine whether or not these are associated with parallel differences in the incidence of acute myocardial infarction. DESIGN: Descriptive epidemiological study. SETTING: Community based study. SUBJECTS: Residents of Auckland, Newcastle and Perth aged 25-64 years admitted to hospital for acute myocardial infarction or dying from coronary heart disease between 1983 and 1987. MAIN OUTCOME MEASURES: Definite acute myocardial infarction or coronary death classified according to the criteria of the World Health Organization MONICA project. RESULTS: This study confirms the marked variation, evident from official statistics, in mortality rates from ischaemic heart disease between Newcastle (high), Auckland and Perth (low). A different pattern is observed for the incidence of acute myocardial infarction and there are also obvious differences between centres in the case fatality ratios for all acute coronary events combined. Newcastle has the highest rate for all coronary events, particularly in women. Auckland is characterised by substantially higher case fatality ratios compared with the two Australian cities. This is due especially to higher rates of coronary death outside hospital. Perth, which has the lowest mortality rates and case fatality ratios in both men and women, has rates for admission to hospital for acute myocardial infarction and all cases of ischaemic heart disease that are disproportionately high in relation to the corresponding mortality rates. CONCLUSION: The differences in case fatality ratios between these three centres are not readily explained by artefacts related to enumeration or classification. Rather, they are most likely related to differences in the natural history of ischaemic heart disease in the three populations. Differences in medical management may also contribute to the substantial variation in mortality rates. PMID- 1921813 TI - Firearm victims--who were they? AB - OBJECTIVE: To determine the characteristics of victims killed by firearms, whether they died by suicide, homicide or accident, and the types of firearms involved. DESIGN: A retrospective and descriptive study. SETTING AND SUBJECTS: Coronial autopsy data were obtained from the Brisbane Laboratory of Pathology and Microbiology. All 587 firearm deaths during the period 1980-1989 were included. MAIN OUTCOME MEASURES: The proportions of deaths by suicide, homicide, accident or undetermined cause. In cases of homicide, we sought to define the relationship of the perpetrator to the victim. RESULTS: The types of death were suicide 76%, homicide 18%, accidents 3% and undetermined 3%. Most homicides were of a domestic nature as opposed to crime. Small calibre rifles were the most common weapon; handguns were rarely used. CONCLUSIONS: Recent debate regarding firearm legislation has failed to recognise the predominance of interpersonal and psychological issues in the causation of firearm deaths. Crime is a motive for only a minority. Medical practitioners may reduce firearm deaths both by organisational representation and individual efforts in clinical practice. In particular, attention should be given to the identification of individuals or families at risk, the detection and treatment of psychological disorder and advice regarding firearm disposal. PMID- 1921814 TI - Where people die in Victoria. AB - OBJECTIVE: To describe where deaths occur in Victoria and to determine to what extent the probability of dying in certain institutions is associated with cause of death and sociodemographic variables. DESIGN: Descriptive study of death certificates and multivariate analysis of 7697 deaths that occurred in a three month period in 1988. SETTING: The State of Victoria. MAIN OUTCOME MEASURES: Cause of death, age, sex, marital status, and socioeconomic status. RESULTS: Most deaths occurred in public hospitals (48%) followed by private homes (21%), nursing homes (14%) and private hospitals (9%). Only 2% of all deaths (90% from cancer) occurred in hospices. Women were more likely to die in a nursing home than were men (21% v. 8%) and less likely to die at home (17% v. 24%). The proportion of deaths increased with age in nursing homes and declined in private homes. Significant predictors of death in a public hospital were age and socioeconomic status; the probability diminished with increasing age and was lower for those in the upper third for socioeconomic status. Predictors for dying in a private home were age and marital status; the probability diminished with age and in the absence of a spouse. CONCLUSIONS: Death as a hospice inpatient is comparatively rare in Victoria and the impact of hospice outpatient or domiciliary care on dying at home has yet to be established. Should death at home become a preferred option, the presence and ability of a spouse or other caregiver will be a significant factor. PMID- 1921815 TI - Problems with training for general practice in South Australia. PMID- 1921816 TI - Non-epilepsy--a clinical perspective. PMID- 1921817 TI - Central Australia: medical practice in Australia's Fourth World. PMID- 1921819 TI - The safety of team midwifery: the first decade of the Monash Birth Centre. AB - OBJECTIVE: To review the safety of team midwifery care, in terms of perinatal mortality, for pregnant women assessed at their first visit as being at low risk of complications. DESIGN: A cohort study. SETTING: Team midwifery unit (Birth Centre) in a tertiary hospital. PATIENTS: All women who made a booking and met the selection criteria at their first antenatal visit (3085), excluding those with spontaneous or induced fetal loss before 20 weeks (89) and those who withdrew at their own request to seek an alternative form of care (138); the 2858 remaining women gave birth to 2874 infants. MAIN OUTCOME MEASURES: Perinatal mortality rate; and birthweight specific perinatal mortality ratio with reference values being specific rates for birthweight in Victoria for 1984-1985. RESULTS: The perinatal mortality rate was 7.7 per 1000 births (95% confidence interval [CI] 4.8-11.6) for the whole cohort; for women beginning labour in the Birth Centre it was 1.3 per 1000 births (95% CI, 0.3-3.9). The birthweight standardised perinatal mortality ratio was 80 (95% CI, 50-122). CONCLUSION: Within this setting, with explicit criteria for booking and referral, and a framework for consultation, team midwifery care is as safe as the standard maternity care provided within the State. PMID- 1921818 TI - Premature ageing of the skin in a Queensland population. AB - OBJECTIVE: To determine the prevalence of premature ageing of the skin and to assess its associations with skin cancer and related risk factors in a Queensland population. DESIGN: Community-based prevalence survey of skin cancer and actinic skin damage. SETTING: Population of Nambour, Queensland, in December 1986. SUBJECTS: Random sample of 1539 residents aged 20 to 55 years for whom skin texture measurements were obtained, and a subsample of 807 whose skin reflectance was measured. MAIN OUTCOME MEASURES: Associations of premature ageing of exposed skin, assessed by silicone moulds of the dorsal skin of the hand, with present or past skin cancer, skin colour measured by reflectance and other related risk factors. RESULTS: Skin texture changes consistent with moderate to severe ageing were observed in 72% of men and 47% of women under 30 years of age. Severity of skin ageing was significantly associated with increasing age, and independently, with the presence of solar keratoses (P less than 0.01) and skin cancer (P less than 0.05). Increased deterioration was also correlated with decreasing reflectance (darker colour) of sun-exposed skin in both men (P less than 0.01) and women (P less than 0.05), but not with reflectance from sun-protected skin, that is inherent skin colour. Photoageing among men was associated with outdoor occupations, outdoor leisure activities, a tendency to sunburn and previous skin cancer. CONCLUSIONS: Marked premature ageing of exposed skin is common in residents of Queensland and is evident among adults in their twenties. Public education programs about the ill-effects of excessive sun exposure should emphasise not only the risk of skin cancer, but also the high risk of premature skin ageing. PMID- 1921820 TI - Neutropenia due to low-dose methotrexate therapy for psoriasis and rheumatoid arthritis may be fatal. AB - OBJECTIVE: To review experience with neutropenia related to low-dose methotrexate therapy in patients with psoriasis and rheumatoid arthritis. DESIGN: Retrospective review of medical records. SETTING: A 509-bed Melbourne teaching hospital. PATIENTS: Five patients admitted in 1987 and 1988, with neutrophil counts of less than 1 x 10(9)/L, given low doses of methotrexate for psoriasis or rheumatoid arthritis. MAIN OUTCOME MEASURES: Death, or length of hospital admission. FINDINGS: Four patients were women, and one a man; three had been treated for psoriasis, and two for rheumatoid arthritis. Ages ranged from 56 to 91 years. The eldest patients, aged 77, 81 and 91 years, died. The other two were discharged after 43 and 48 days. Prior to or shortly after admission, four patients were treated with penicillin antibiotics which may have interfered with methotrexate excretion. CONCLUSIONS: Methotrexate clearances (related to creatinine clearance rates and presumably low) were probably reduced sufficiently by concomitant therapy to result in neutropenia. Practitioners using methotrexate should be aware of drug interactions resulting in delayed methotrexate excretion. Blood counts should be monitored after changes in therapy, especially in patients with impaired renal function, such as the elderly. PMID- 1921821 TI - Terminal restlessness--its management and the role of midazolam. AB - OBJECTIVE: To describe the clinical picture of the syndrome of terminal restlessness in dying patients and the role and mode of administration of midazolam. SETTING: Hospice unit of a public hospital. DESIGN: Retrospective review of patient records and search of the literature for reports of the use of midazolam in palliative care from 1988 to 1990 and of the effects and side effects of drugs commonly used in the management of terminal restlessness. PATIENTS AND INTERVENTION: Eighty-six patients with terminal restlessness received midazolam to alleviate their symptoms. MAIN OUTCOME MEASURES: Improved relaxation in the patients, a reduction in family anxiety and reduced staff stress. RESULTS: Of the 86 patients with terminal restlessness, all but one obtained benefit. No apparent side effects or adverse reactions to the drug were observed. CONCLUSION: Midazolam given by the subcutaneous route can usually provide effective palliation of terminal restlessness when other measures are ineffective. The drug is also useful for providing short-term sedation for uncomfortable procedures and for managing catastrophic terminal events. PMID- 1921822 TI - Treatment of bipolar disorder. AB - OBJECTIVE: To review the current status of the management of bipolar disorder (manic-depressive illness). DATA SOURCES AND STUDY SELECTION: Controlled clinical trials as well as some recent important open studies are examined. DATA EXTRACTION AND SYNTHESIS: Lithium carbonate remains the mainstay of both the acute and prophylactic treatment of this condition. We highlight specific contentious issues in prophylactic management with lithium, that is, indications for initiating long-term treatment, preferred serum concentrations, timing of the dose, duration of treatment and frequency of laboratory monitoring. In recent years, several alternatives to lithium have been demonstrated as effective in both the acute and prophylactic treatment of patients either unable to tolerate or inadequately responsive to this agent. There is now considerable evidence that carbamazepine is of similar efficacy to lithium and more recent studies suggest that valproate may also be as therapeutic. We outline details of the clinical roles of each of these agents, with guidelines concerning monitoring and adverse effects. PMID- 1921823 TI - Pancytopenia after accidental overdose of methotrexate. A complication of low dose therapy for rheumatoid arthritis. AB - OBJECTIVE: Pancytopenia is an unusual complication of low-dose methotrexate therapy in rheumatoid arthritis. We report a near fatal case that followed an accidental overdose. CLINICAL FEATURES: An 80-year-old Caucasian woman with rheumatoid arthritis presented with pancytopenia and severe mucositis. She had taken her weekly methotrexate dose on four sequential days, due to an error in filling a "Dosette" box. INTERVENTION AND OUTCOME: Following treatment with piperacillin, gentamicin and folinic acid, she recovered completely. CONCLUSIONS: Low-dose methotrexate therapy is uncommonly associated with haematological toxicity. This generally occurs in patients with known risk factors for such reactions. Patient reliability should be considered if methotrexate therapy is contemplated. PMID- 1921824 TI - Cholesterol testing. The Australasian Epidemiological Association. PMID- 1921825 TI - Surgeon Alexander Denmark, Physician to the Mediterranean Fleet. PMID- 1921826 TI - Providing medical care for deaf patients. PMID- 1921828 TI - REM reprocessing. PMID- 1921827 TI - Medical causes of male sexual dysfunction. PMID- 1921829 TI - Aerosol spray for arthritis. PMID- 1921831 TI - HIV epidemic and the apparent misrepresentation. PMID- 1921830 TI - Planned homebirths in Western Australia. PMID- 1921832 TI - Of ends and means. PMID- 1921833 TI - Thyroid histopathology in south-west Sydney. PMID- 1921834 TI - Giant cell arteritis presenting as transient microscopic haematuria. PMID- 1921835 TI - Seeing red. PMID- 1921836 TI - On living with rheumatoid arthritis. PMID- 1921837 TI - Recent patterns of tobacco smoking in Japan. PMID- 1921838 TI - Rural doctor training. PMID- 1921839 TI - Terminology of medical/hospital waste: infectious or contaminated. PMID- 1921840 TI - [Leukotrienes]. PMID- 1921841 TI - [Chronic glaucoma. Aids for early detection]. PMID- 1921842 TI - [Folic acid and vitamin deficiency caused by oral contraceptives]. PMID- 1921843 TI - [Immunotherapeutic agents in infections?]. PMID- 1921844 TI - [Zidovudine in asymptomatic HIV infection]. PMID- 1921846 TI - Sanctity of life. PMID- 1921845 TI - Rationing health care: ethical and legal considerations and QALYs. PMID- 1921847 TI - The human genome--any questions? PMID- 1921848 TI - Football hooliganism, delinquency and public health. PMID- 1921849 TI - Medicine and the courts. PMID- 1921850 TI - Increased collagen gene expression in vascular smooth muscle cells cultured in serum or isoleucine deprived medium. AB - The relationship between type I and type III collagen gene expression and the growth state of cultured bovine vascular smooth muscle cells has been investigated. Growth was modulated by incubation of subconfluent cultures of smooth muscle cells in media containing concentrations of fetal calf serum ranging from 10% to 0.5%. As the serum concentration was lowered, the doubling time increased from 17 hours to 70 hours, and collagen mRNA levels increased as judged by Northern blot analysis. The levels of induction were 5- to 15-fold for alpha 1(I), 2- to 3-fold for alpha 2(I), and 4- to 7-fold for alpha 1(III). Metabolic cell labelling with precursor amino acids indicated that type I and type III procollagen synthesis was elevated approximately 2-fold as growth slowed. A similar 2-fold increase occurred upon translation of isolated RNAs in a rabbit reticulocyte cell-free system. Nuclear run-on analysis indicated that increased collagen transcription can account for part of the increase in mRNA levels following incubation in lowered fetal calf serum. To further examine the influence of proliferation on collagen gene expression, smooth muscle cells were cultured in isoleucine-free medium, which resulted in quiescence within 36 hours. Induction of collagen mRNA levels was observed within 24 hours of incubation in isoleucine-free medium. Thus, collagen gene expression increases as the growth of vascular smooth muscle cells is slowed by either deprivation of growth factors or essential amino acids. Regulation is mediated at several sites, including gene transcription and mRNA translation, and possibly post-transcriptional steps. PMID- 1921851 TI - Desmoplasia in benign and malignant breast disease is characterized by alterations in level of mRNAs coding for types I and III procollagen. AB - Desmoplasia, the formation of excessive connective tissue surrounding some neoplasms, is a well documented, but incompletely understood phenomenon. To characterize the fibrotic response in benign breast conditions and malignancy, we examined the steady state levels of mRNA coding for types I and III procollagen in mild fibrocystic changes, in fibroadenoma, and in infiltrating ductal carcinoma. The results indicate that in mild fibrocystic change there is a relative increase in type III procollagen mRNA. In contrast, fibroadenoma and carcinoma are characterized by increased levels of type I procollagen mRNA. PMID- 1921852 TI - Regeneration of rat extensor digitorum longus tendon: the effect of a sequential partial tenotomy on collagen fibril formation. AB - Alterations in collagen fibril diameter distribution were measured in rat extensor tendons subsequent to two-successive partial tenotomies, 30 days apart. Subsequent to surgery three areas were created. The primary lesion area, consisted of a regenerating window in the central half of the tissue. Secondary lesion areas consisted of strips at the lateral margin of the tissue, removed during the second operation. Between the lesion areas were the non-lesion areas consisting of tissue not removed during surgery. Tissue was examined 40, 60, 120 and 240 days after the initial operation. Within each group, primary and secondary lesion areas remained unimodal in collagen fibril diameter distribution throughout the period of the study. This distribution was initially unimodal in the non-lesion areas but became multimodal by 240 days postoperatively. Both the primary lesion area and non-lesion areas exhibited an increase in frequency of small diameter fibrils between 40 and 60 days postoperatively. It is suggested that all observations may be related to the level of applied stress. PMID- 1921853 TI - Transforming growth factor-beta 2 enhances the osteoinductive activity of a bovine bone-derived fraction containing bone morphogenetic protein-2 and 3. AB - We previously identified a novel glycoprotein in an osteoinductive fraction from bovine bone (Bentz et al.: Amino acid sequence of bovine osteoinductive factor. J. Biol. Chem. 265: 5024-5029, 1990). We now find that this fraction also contained small amounts of bone morphogenetic protein-2 and 3 (BMP-2 + 3) previously identified by others (see Wozney, J.M.: Bone morphogenetic proteins. Prog. Growth Factor Res. 1: 267-280, 1990). Separation of BMP-2 + 3 from the glycoprotein was achieved with a modified reversed phase-high pressure liquid chromatographic procedure. When assayed in the rat subcutis using a collagen ceramic carrier, the osteoinductive activity was found in the subfraction containing BMP-2 + 3. This activity was potentiated and the ratio of cartilage to bone was increased by transforming growth factor-beta 2. The glycoprotein, originally called osteoinductive factor, has been renamed osteoglycin. In its precursor form, osteoglycin is a member of the leucine-rich family of proteins showing the characteristic 24-residue internal homology. Its biological function is unknown. PMID- 1921854 TI - Type IX collagen gene expression during limb cartilage differentiation. AB - Changes in the steady-state levels of mRNAs for the alpha 1(IX) and alpha 2(IX) polypeptide chains of cartilage-characteristic type IX collagen were examined during the course of chick limb chondrogenesis in vitro and in vivo. Cytoplasmic type IX collagen mRNAs begin to accumulate at the onset of overt chondrogenesis in high density micromass culture coincident with the crucial condensation phase of the process, in which prechondrogenic mesenchymal cells become closely juxtaposed prior to depositing a cartilage matrix. The initiation of type IX collagen mRNA accumulation at condensation coincides with the initiation of accumulation of cartilage proteoglycan core protein mRNA and with a striking increase in type II collagen mRNA accumulation. Following condensation in vitro, there is a concomitant progressive increase in cytoplasmic type IX collagen, core protein, and type II collagen mRNA levels which parallels the progressive accumulation of cartilage matrix. Type IX collagen mRNAs also begin to accumulate at the initiation of overt chondrogenesis in vivo in the chondrogenic central core of the developing limb bud. In contrast, little, or no type IX collagen mRNAs are detectable in the nonchondrogenic peripheral regions of the developing limb bud. PMID- 1921855 TI - To reconstitute skin: theme and variations. PMID- 1921856 TI - 140-MDa plasmids of Escherichia coli and Shigella flexneri 5 do not influence phagocytosis. AB - Enteroinvasive Escherichia coli (EIEC) and Shigella flexneri possessing a 140 megadalton (MDa) plasmid are capable of invading intestinal epithelial cells and causing dysentery. To determine if this plasmid affected phagocytosis of the organisms by leukocytes, we studied the in vitro phagocytosis of isogenic pairs of EIEC and S. flexneri 5 which differed only in the presence or absence of the 140-MDa plasmid. In addition five EIEC strains containing 140-MDa plasmids as well as one non-enteroinvasive E. coli strain possessing a 120-MDa plasmid were studied. The 140-MDa plasmid did not affect phagocytosis of these bacteria by normal human blood neutrophils or monocytes. PMID- 1921857 TI - Importance of experimental design in the evaluation of the influence of proteins in bacterial adherence to polymers. AB - The use of intravascular catheters is frequently associated with coagulase negative staphylococcal infections. Colonization of catheters depends on the ability of bacteria to attach to artificial surfaces, this process is affected by macromolecules present in the body fluids. We determined the adherence of five coagulase-negative strains onto polyethylene, nylon and polyvinyl-chloride catheters, after treatment of bacteria, catheters or both with citrated human plasma, human serum albumin or fibrinogen. Plasma and serum albumin produced a marked inhibition of bacterial adherence (P less than 0.05) by means of adsorption on biomaterial surface. Fibrinogen enhanced (P less than 0.05) the number of bound bacteria, specially through its interaction with the staphylococcal surface. These observations suggest the possible role of plasma proteins in these infections. PMID- 1921858 TI - [The epidemiological status of malignant diseases in the region of Subotica 1976 88]. AB - In this paper the author presents the results of the analysis of the information of the malignant diseases register of the Oncology Department of the General Hospital in Subotica. The observation time lapse took place from 1976 to 1988 and was related to the entire territory of the Subotica Community. In the course of thirteen years, the total number of deceased persons amounted to 25,490, an average of 1960. The total number of persons affected with carcinoma was 6972, an average of 536 annually. The number of persons who died of cancer amounted to 4217, which means an average of 324 per annum. The average annual carcinoma incidence recorded came to 346, the average annual cancer mortality was 214, and the average overall mortality 1292. The average share of cancer mortality in the overall mortality amounted to 16.5%. Presented are the movement trends of the overall cancer incidence and mortality for the entire territory of the Subotica Community, as well as for it's larger settlements. A morbidity and mortality structure is given according to the frequency of particular cancer localizations, as well as the incidence and mortality movement trends of the most frequent carcinomas. PMID- 1921859 TI - [Diagnostic characteristics of the CA-50 and CA 72-4 tumor markers in body fluids. Use in the diagnosis of malignant effusions]. AB - The paper presents the results of a comparative investigation of CA-50 and CA 72 4 in the serum and effusions of the control group and a group of patients with various localizations of malignant tumors. The diagnostic applicability of CA-50 in the serum is limited by a substantial extent of falsely positive results, which is not the case with CA 72-4. Malignant cells make a more intensive release of CA 72-4 into effusions than into the blood, and the situation with CA-50 is reverse. It has been established that CA-50 in the serum and that CA 72-4 in effusions are complementary parameters. Markers in effusions have more favorable diagnostic characteristics in relation to serum. Although CA 72-4 is of a more superior diagnostic reliability, the examining of both markers is of help in the differentiation of benign peritoneal and pleural effusions from the malignant ones. The persistence of these markers in body fluids does not indicate the primary origin of malignant tumors. PMID- 1921860 TI - [Quality of life]. AB - The term "Quality of life" appeared at the end of the fifties of this century, it seems in the philosophical and sociological vocabulary at first, and soon after that it became adjusted in medical and non-medical (politics, ethology, mass media) use. In the last few years this term has been used all the more frequently in different branches of medicine because of a more extended human lifetime, due to the development of medicine, the domination of chronic diseases in the pathology of well-developed environments, and because of the growing influence of socio-psychological viewpoints in the bounds of medicine as well. Time will show whether only a transient, "fashionable" term is in question, or if a lasting survival in medical vocabulary has been ensured. This paper analyses the development and the contents of the quality of life concept, it's ethical connotation, the application in different branches of medicine, as well as the principals and problems of it's measurement for clinical purposes. The literature contributed includes 75 domestic and foreign authentic references. PMID- 1921861 TI - [Management of preterm breech presentation]. AB - At the department for Obstetrics and Gynecology in Zagreb we analyzed 342 preterm singleton breech deliveries during three different periods of time: the first from 1975-1978, the second from 1982-1986, and the most recent one from 1987 1989. All studied cases were infants with birth weight of 1.200 gr or more. Out of 135 infants born in the first time interval, the Bracht maneuver was employed in 90 (66.6%) cases; 13.3% of vaginal deliveries from the same time interval were managed by partial extraction, and total etraction was applied in 3.7% of vaginal deliveries. The cesarean delivery rate was 16.3% in the first analyzed period. From 1982-1986, 79 (67.5%) out of a total of 117 infants were delivered vaginally by the Bracht maneuver, 3.4% by partial extraction, and only one child was delivered by total extraction. In this time interval, 28.2% of all deliveries were terminated by cesarean section. In the most recent interval from 1987-89, our attitude towards preterm breech delivery has completely changed. The Bracht maneuver was applied in only 32.2% out of a total of 90 born infants, and partial extraction in 3.3%. None of the infants were delivered by total extraction. The cesarean section rate doubled and amounted to 64.4%. Nevertheless, the best indicator of results is the perinatal mortality of infants according to the observed time intervals. Perinatal mortality in the first period was 20%, in the second period it was 12% and 5.6% in the third period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921862 TI - [Rubeola in the population of Subotica 1978-1989]. AB - The circulation of acute rubeola in the population of Subotica was analyzed from 1978 to 1989 regarding general and specific morbidity, the periodicity of occurrence and the cyclic increase in frequency. On the basis of a set clinical diagnosis 11246 cases of rubeola have been registered. Vaccination against rubeola is not conducted in Subotica, therefore this viral contagious disease has an endemoepidemic course. The highest epidemic waves have been registered in 1981 with 2117, and in 1984 with 2662 reported persons. The greatest agglomeration of those affected is in the age group of 5 to 9 years with 4475 (39.79%) of cases. The epidemic waves are divided by two calmer interepidemic periods in 1982 and 1983 as well as in 1986 and 1987. In the population of Subotica the occurrence of acute rubeola is increased at the end of winter with a predomination in the spring months. PMID- 1921863 TI - [Medical informatics and health care in Subotica yesterday, today and tomorrow]. AB - The application of information systems in health care throughout the world has begun ten years after the first generation of computers. Computers are a tool for doing business in all segments of health care. After a presentation of the development of informatics in the world and in our surroundings, a survey of events related to the health-care informatics in Subotica is given, as well as the perspective which is expected. PMID- 1921864 TI - [The terminal ileum and chronic diarrhea: endoscopy, histology and parasitology]. AB - In 53 patients with chronic diarrhea ileoscopy was done following colonoscopy. Beside the microscopic examination, terminal ileum biopsies and mucosal smears were also performed. Endoscopy of the terminal ileum was abnormal in eight patients (15.1%); biopsy itself was diagnostic in 22 patients (41.5%): primary bile acid malabsorption with mucosal atrophy and reduced retention of 75ScHCAT (10), mucosal atrophy after cholecystectomy (4), Crohn's disease (6), backwash ileitis in ulcerative colitis (1), and postirradiation ileitis (1). Biopsies were normal but mucosal smear indicated the cause of diarrhea in a further 10 patients: giardiasis was found in 7, and candidiasis in 3 patients. All in all, endoscopy, biopsy and mucosal smear of terminal ileum showed a sensitivity of 58.5%. In 38 patients in whom laboratory, roentgenologic and endoscopic investigation failed to establish the etiology of diarrhea, the sensitivity of ileoscopy itself was 0%, of ileoscopy with biopsy 36.8% and ileoscopy with biopsy and mucosal smear 47.4%. We conclude that endoscopy, biopsy and mucosal smear of the terminal ileum are indicated in the investigation of patients with chronic diarrhea. PMID- 1921865 TI - [Primary liver carcinoma in the Subotica City Hospital 1962-1990]. AB - The authors have presented their observations in 108 pathologically processed cases of primary hepatic carcinoma (PHC). The material includes the period from 1962 to 1990. The most frequent form of PHC was hepatocellular (67.5%), the cholangiocellular (29.5%) and rarest, the mixed hepato-cholangiocellular form (2.9%). X-ray diagnostics were applied (celiacography, arteriography), laparoscopy, ultrasonography, aimed and blind aspirational biopsy, and laboratory examinations (alkaline phosphatase, transaminases, bilirubin, gamma-CT and so on). Somewhat more attention is given to the problem of HBV infection as the cause of primary hepatic carcinoma development. Pre-existing liver tissue diseases are also pleaded for (chronic aggressive hepatitis, hepatic cirrhosis, ect.). Beside the many diagnostic procedures, the diagnosis of primary hepatic carcinoma is usually established too late, and the therapy still remains unsatisfactory. PMID- 1921866 TI - [Problems of nutrition in school children in Subotica and its importance to health]. AB - The aim of this paper was to determine the characteristics of the nutrition of primary school children in Subotica and to perceive the health hazards of such nutrition. A deficit of animal proteins, certain vitamins and minerals as well as surplus of fats was determined in the quality follow-up of additional meal in schools. In family nutrition, apart from the already known qualitative deficits, an irregular rhythm of taking meals was also evidenced, because about 24% of pupils do not have breakfast. The established irregularities of family and communal feeding can be one of the causes of appearance of the diseases due to deficient or surplus nutrition in pupils of Subotica. Because of this it is necessary to provide optimal communal feeding and to include as much pupils as possible in the aim of correcting family nutrition and the prevention of nutritive and health hazards. PMID- 1921867 TI - [Tracing the written word in the development of medical thought in Subotica during the last 3 centuries (1690-1990)--250 years of health care in Subotica- (1740-1990)]. PMID- 1921868 TI - [Little understanding of the poor, ill and abandoned in Subotica at the end of the 18th and first half of the 19th century]. PMID- 1921869 TI - [Founders of medical science and health services in Subotica 1792-1991]. PMID- 1921870 TI - [Development of the laboratory service in the OOUR health facilities]. PMID- 1921871 TI - [Evacuation of the Subotica General Hospital during peace conditions]. PMID- 1921872 TI - A linear array, scintillation crystal-photodiode detector for megavoltage imaging. AB - An imaging device has been developed to acquire images during external photon beam radiotherapy treatments. It consists of a linear array of 128 zinc tungstate (ZnWO4) scintillation crystals each of which is individually optically coupled to a photodiode and associated electronics. The image is formed by scanning the linear array across the radiation field using a stepping motor under the control of a microcomputer. Image archive, display, and analysis are performed using a microVAX II computer. Results from a general theoretical analysis are presented before a detailed description of the particular detector construction. The mechanical design of the detector is such that the detector is automatically positioned to within a millimeter relative to the treatment source. This simplifies procedures for analyzing setup variations when comparing a treatment image to any other treatment, or planning, images. Image acquisition takes under 4 s with a contrast resolution of better than 1% at a spatial resolution of 2.5 mm in the object plane. The primary dose used to form these images is 0.55 cGy although the dose received by the patient will be closer to 25 cGy due to the linear scanning geometry and 3.8-s scan time that is used. PMID- 1921873 TI - Physical aspects of a liquid-filled ionization chamber with pulsed polarizing voltage. AB - The charge collection in a liquid-filled matrix ionization chamber system has been investigated. This system, which is used for megavoltage radiography, is scanned electronically by switching the polarizing voltage. In such a system the charge collection cannot be described by the classical ionization chamber theory since this is only valid for a fixed polarizing voltage. A model is presented for an ideal plane-parallel ionization chamber with switched polarizing voltage that gives a good qualitative description of the physical phenomena in our nonideal system. The new model predicts the amount of charge collected and the signal-to noise ratio as a function of several parameters such as electrode distance, polarizing voltage, radiation intensity, and some liquid characteristics. An important result is that the quantum noise contribution can be made quite small. This situation occurs in liquids with a low ion mobility and long ion lifetimes by a charge-integrating effect in the liquid. Experiments were performed to test various aspects of the model. A reasonable agreement is found between theoretical and experimental results. The possible use of ultrahigh-mobility liquids is also discussed. PMID- 1921874 TI - Potential and limitations of invariant kernel conformal therapy. AB - A treatment planning methodology was developed to investigate the invariant kernel form of conformal therapy proposed by Brahme. Three-dimensional dose distributions were calculated by convolving a rotationally symmetric, invariant kernel with weighting distributions. Fourier transform convolution techniques implemented on an array processor were used to achieve high calculation speeds, thereby allowing iterative techniques in the spatial and frequency domains for computing dose distributions that asymptotically approach a desired dose distribution. To use rotationally symmetric kernels, the generality of the solution is traded for a fast, deterministic, inverse planning approach. The limitations imposed on the dose distributions by this loss of generality are characterized and tentative conclusions are drawn about the potentials and limits of clinical application of this form of the methodology. Further developments of the concept are suggested. PMID- 1921875 TI - Dose perturbations at interfaces in photon beams: annihilation radiation. AB - A model is presented for estimating the contribution of annihilation radiation to the dose perturbation at interfaces between high and low atomic number materials. The contribution is small, but not negligible relative to the total interface dose perturbation. The maximum contribution occurs for photon beams of about 8 MeV in energy. For an 8-MeV beam passing first through lead, then through polystyrene, the annihilation radiation contribution to the interface dose perturbation is about 8%, at a copper/polystyrene interface, the contribution is about 7%, and at an aluminum/polystyrene interface, the contribution is about 3%. PMID- 1921876 TI - A modified power-law formula for inhomogeneity corrections in beams of high energy x rays. AB - The Batho power-law formula is in common use in many treatment planning systems to correct for the presence of lungs and other inhomogeneities. While giving excellent agreement with measurement for Cobalt-60 radiation, it tends to underestimate the lung correction required for higher energy x rays and is undefined for distances beyond an interface less than the buildup distance. This paper suggests a simple modification that greatly improves the agreement with measured data and gives a continuously defined function at all depths. Measurements have been made in a polystyrene and cork phantom to simulate the effects of lung; data are presented for beams of 8-MV x rays, 16-MV x rays, and Cobalt-60 gamma rays. PMID- 1921877 TI - A mathematical expression for %DD accurate from Co-60 to 24 MV. AB - Obtaining accurate %DD values for routine treatment calculations is essential in radiation therapy. Many papers have presented expressions to calculate this or related parameters but these expressions often required that the parameters needed by the equation be determined for each individual treatment unit. This paper presents an expression that calculates %DD values with a mean-square accuracy of approximately 1.0% versus measured values. The expression is applicable to beam energies ranging from Co-60 to 24 MV, field sizes from 4 X 4 to 40 X 40 cm2, and depths from 1 cm deeper than dmax to 30 cm. The only information required by this expression that is machine specific is the ionization ratio. PMID- 1921878 TI - Angular distribution of bremsstrahlung from 15-MeV electrons incident on thick targets of Be, Al, and Pb. AB - Bremsstrahlung spectra from thick cylindrical targets of Be, Al, and Pb have been measured at angles of 0 degrees, 1 degree, 2 degrees, 4 degrees, 10 degrees, 30 degrees, 60 degrees, and 90 degrees relative to the beam axis for electrons of 15 MeV incident energy. The spectra are absolute (photons per incident electron) and have a 145-keV lower-energy cutoff. The target thickness were nominally 110% of the electron CSDA range. A thin transmission detector, calibrated against a toroidal current monitor, was placed upstream of the target to measure the beam current. The spectrometer was a 20-cm-diam by 25-cm-long cylindrical NaI detector. Measured spectra were corrected for pile-up, background, detector response, detector efficiency, attenuation in materials between the target and detector and collimator effects. Spectra were also calculated using the EGS4 Monte Carlo system for simulating the radiation transport. There was excellent agreement between the measured and calculated spectral shapes. The measured yield of photons per incident electron was 9% and 7% greater than the calculated yield for Be and Al, respectively, and 2% less for Pb, all with an uncertainty of +/- 5%. There was no significant angular variation in the ratio of the measured and calculated yields. The angular distributions of bremsstrahlung calculated using available analytical theories dropped off more quickly with angle than the measured distributions. The predictions of the theories would be improved by including target-scattered photons. PMID- 1921879 TI - The effects of a universal wedge and beam obliquity upon the central axis dose buildup for 6-MV x rays. AB - In a number of clinical situations, the dose to the skin and the superficial tissues is of concern. Both beam obliquity and a beam modifier will modify the dose delivered to these regions due to changes in the scattering geometry, scattered photon and secondary electron production, and changes in the energy spectrum of a polyenergetic beam. Some linear accelerators use a single universal wedge mounted within the treatment head. Because such a wedge is at an extended distance from the patient, its contribution to the beam contaminants incident to the skin will be limited. Measurements of the ionization in the buildup region have been performed in a polystyrene phantom irradiated with a 6-MV x-ray beam from a linear accelerator equipped with a universal wedge. The variation of the buildup dose with obliquity, universal wedging, and distance from the source has been measured for angles of incidence between 0 degrees and 60 degrees and for effective wedge angles between 0 degrees and 45 degrees. The results indicate that the percentage buildup has a much stronger dependence upon the angle of incidence than upon the effective wedge angle. For distances approaching the treatment head, it is shown that the universal wedge generates secondary electrons that elevate the surface dose, but that this contribution decreases with distance. PMID- 1921880 TI - Primary dose in photon beams with lateral electron disequilibrium. AB - It is shown that in narrow monoenergetic photon beams under conditions of lateral electron disequilibrium, primary absorbed dose P(r) is a simple function of beam radius r: P(r) = P lambda.(1 - e(-gamma.r)), where P lambda is the primary dose in broad beams for which complete lateral electron equilibrium exists, and gamma depends on photon energy and absorbing medium. This formula was evaluated using Monte-Carlo-generated data for the primary dose in water from monoenergetic photons in the energy range from 2 to 8 MeV. The primary dose was studied in beams of radii 0.006 cm less than r less than 5.0 cm and within the depth interval 0.5 cm less than or equal to d less than or equal to 24 cm. It was concluded that the saturation equation above provides an accurate description of the primary dose from monoenergetic photon beams, as judged by comparison with Monte Carlo results. PMID- 1921881 TI - Ngas values of the Memorial parallel-plate chambers determined in 60Co and high energy electron beams. AB - The cavity-gas calibration factor Ngas for Memorial parallel-plate chambers was determined against calibrated Farmer chambers using two different calibration methods as suggested in the TG 21 protocol. These methods are: (a) 60Co calibration at 5-cm depth; and (b) high-energy electron beam calibration. The Ngas values determined from the 60Co in-phantom calibrations were approximately 1.9% higher than the values determined from the high-energy electron beams. PMID- 1921882 TI - Comparison of the penumbra between focused and nondivergent blocks--implications for multileaf collimators. AB - The penumbra from a 10-MV x-ray beam has been measured using various field shaping blocks located in the normal blocking tray position and compared to the penumbra of the adjustable photon jaws of the machine. The results showed that the penumbra was substantially degraded by these blocks only for field sizes greater than 15 x 15 cm2 and at the depth of maximum dose, dmax. At depths of 11 cm or greater, there was a significant difference only for the same range of field sizes in the 80% to 50% dose region. There was no significant difference at these depths for either the 95%-50% or the 90%-50% dose regions. No significant difference was observed between the use of lead and tungsten blocks and also between lead blocks with a straight edge and those with either an 0.5-mm or a 1 mm step in the face. Since the width of the 95% dose relative to the 50% dose is of greatest interest clinically, straight-edged blocks are as effective as divergent blocks in most situations. These results imply that the design and complexity of a multileaf collimator can be greatly simplified from a double focusing device to one that is single focusing in the plane orthogonal to the leaves. PMID- 1921883 TI - Modeling of asymmetric compensator geometries. AB - Dose distributions arising from the use of near unit density retracted missing tissue compensators in symmetric geometries have been successfully modeled on the basis of primary and first-order scattered radiation. This method of analysis has been extended to both low- and high-density materials in asymmetric geometries. Good agreement is achieved between theory and experiment. PMID- 1921884 TI - Corner transmission in several linear accelerator photon beams. AB - Maximum x-ray field sizes on many linear accelerators are obtained only with truncated corners. Transmissions through the corners of such fields has been measured utilizing film and ion chamber dosimetry for a number of accelerators. Transmissions are found to be significantly larger than for the movable jaws. PMID- 1921885 TI - Spherical harmonic expansion of cranial surfaces. AB - A three-dimensional analytical technique for the representation of the cranial surface based on a spherical harmonic expansion is presented. The analytical surface representation is used in conjunction with a sample iterative ray intersection algorithm to compute the dose calculation depth. The technique is compared to other conventional techniques and it is determined that the spherical harmonic approach of approximating the cranial surface decreases the depth calculation time by approximately a factor of 60. PMID- 1921886 TI - Photon energy dependence of the sensitivity of radiochromic film and comparison with silver halide film and LiF TLDs used for brachytherapy dosimetry. AB - There is a new radiochromic film, a highly uniform, thin (100-microns) detector whose sensitive layer (6 microns thick) changes from colorless to blue by dye polymerization without processing, upon exposure to ionizing radiation. Because the dose gradients around brachytherapy sources are steep, the high spatial resolution offered by film dosimetry is an advantage over other detectors such as thermoluminescent dosimeters (TLDs). This compares the photon energy dependence of the sensitivities of GafChromic film, silver halide verification film (Kodak X Omat V Film), and lithium fluoride TLDs (Harshaw), over the photon energy range 28 keV to 1.7 MeV, which is of interest in brachytherapy. Sensitivity of the radiochromic film is observed to decrease by about 30% as effective photon energy decreases from 1710 keV (4-MV x rays) to 28 keV (60-kV x rays, 2-mm A1 filter). In contrast, the sensitivity of verification film increases by 980% and that of LiF TLDs increases by 41%. The variation of the sensitivity of radiochromic film with photon energy is considerably less than that for silver halide film and similar to that for LiF TLDs, but in the opposite direction. Radiochromic film, like LIF TLDs, does not exhibit the drastic sensitivity changes below 127 keV that silver halide film exhibits. Dose distribution in the immediate vicinity of a high activity (370 GBq) brachytherapy 192Ir source has been mapped using radiochromic film and is presented to illustrate the applicability of this new technology to brachytherapy dosimetry. PMID- 1921887 TI - Comparison of measured and calculated dose rates in water near I-125 and Ir-192 seeds. AB - Recent theoretical and experimental work indicates that currently accepted 125I dosimetry data may overestimate dose in water at 1 cm by 10%-24%. Among the most comprehensive measurements are those of the NCI-sponsored brachytherapy contract participants. Absolute dose rates in water calculated by the Monte Carlo method have been compared with the NCI dose measurements about 125I and 192Ir seeds embedded in solid-water phantoms. The photon transport code allows realistic geometric simulation of the complex internal seed structure, the National Institute of Standards and Technology air-kerma strength standardization geometry, and the dose measurement setup. When the appropriate measurement medium and geometry are assumed, agreement between theory and measurement is excellent, within 3% at 1 cm and averaging 3% at larger distances. However, the data do not support the water equivalence of solid water at 125I energies indicating that solid-water measurements underestimate 125I specific dose-rate constants in water by 4.3%. Because of its higher ratio of absorption to scatter, 125I dose distributions measured in solid water are less penetrating (by 35% at 10 cm) than those measured in liquid water. For model 6711, model 6702, and steel-clad 192Ir seeds, Monte Carlo calculations yielded specific dose-rate constants (assuming liquid water medium) of 0.877, 0.932, and 1.122 cGy cm2 h-1 per unit air-kerma strength, respectively. For 125I, currently accepted values are 18% and 11% larger for the two seed models. PMID- 1921888 TI - Calibration of ophthalmic applicators at NIST: a revised approach. AB - A revised approach to the problem of measuring a surface-absorbed dose from beta particle-emitting ophthalmic applicators is presented. The technique chosen employs an extrapolation chamber equipped with a 4-mm-diam collecting electrode to make current measurements at air gaps from 0.08 to 0.20 mm at 0.02-mm intervals. These data yield a linear relationship between current and air gap, the slope of which is used to determine average surface-absorbed-dose rate over the central area of the source. For additional information about the distribution of the activity over the source surface, autoradiographs using calibrated radiochromic dye films are analyzed to map the dose-rate profile across the surface of the applicator. Experiments varying several parameters of the extrapolation chamber measurement, including collecting electrode area, voltage gradient, range of air gaps used, and entrance foil material, are described. Also treated are calibrations of, and a description of the use of, radiochromic dye films for source profiling. Experiments for determining correction factors for the extrapolation chamber measurements are described, and an assessment of the uncertainties associated with these measurements is given. PMID- 1921889 TI - Thermodynamics of movable inductively heated seeds for the treatment of brain tumors. AB - A thermodynamic study is presented of temperature distributions created by an inductively heated 6-mm-diam Ni sphere imbedded in vivo and in vitro into porcine brain tissue. This study was performed in support of the development of a system that creates localized heat-induced lesions in deep-seated brain tumors. In this system, a magnetic "seed" will be remotely repositioned within the brain by an externally produced magnetic field. Convective effects of a hot moving seed will produce a different thermodynamic situation than that arising from an array of static implants. In this work, a study is presented of part of the expected change, in which a static sphere is heated to high temperature. Measurements were made of the temporal and spatial dependence of the temperature rise in the vicinity of the heated sphere, in vivo in four animals and in one that was euthanized immediately prior to experimentation. These results are used for parameter estimation with a theoretical model based on a point source solution to a form of the thermal diffusion equation, i.e., the "bioheat transfer equation." With this model thermal distributions from a power source of arbitrary geometry can be found using appropriate integration methods, and the method has widespread applicability. Estimates of blood flow rates, tissue thermal conductivity, and seed power absorption were found using the parameter estimation algorithm. The estimated blood perfusion exhibits a step increase following the first heating in multiple heating experiments. Thermal conductivity estimated using data from the nonperfused (in vitro) animal is 0.6 W/m degrees C. Seed power absorption is estimated correspondingly to be 0.9 W, a result confirmed independently with calorimetry. Statistical uncertainty is established for the radial decrease of the tissue temperature rise created by this method. This result allows estimation of a cell death boundary uncertainty of 0.6 mm, caused by fluctuations in power delivered to the seed, uncertainty in the temperature probe placements, and thermal properties such as blood perfusion and tissue thermal conductivity. PMID- 1921890 TI - Exact determination of the magnification factor for target lesions in a stereotactic frame. PMID- 1921891 TI - Characteristic parameters of 6-21 MeV electron beams from a 21 MeV linear accelerator. AB - Dosimetry measurements have been carried out for the electron beams produced by a linear accelerator at energies 6, 8, 10, 14, 18, and 21 MeV. Characteristic parameters of the central axis dose distributions were derived and compared to corresponding values of electron beams from other accelerators in clinical use where such a comparison is appropriate. A comprehensive set of dosimetric parameters is provided for electron beam treatment planning. The data include central axis depth dose, range-energy parameters, beam penumbra and uniformity. PMID- 1921892 TI - Dosimetric investigations in the dose buildup using bolus techniques for fast neutron therapy. AB - A moulded bolus is commonly used to compensate for contour irregularities of patients treated with fast neutrons. The bolus material should have the same attenuation characteristics as tissue, should be easily mouldable and sufficiently solid for multiple applications. For fast neutron beams, the mixture of equal parts of beeswax and paraffin is a suitable bolus material. As in photon beams the bolus, when placed directly on the patient skin, removes completely the skin sparing effect. However, in neutron beams the dose buildup can mostly be recovered by lining the bolus surface in contact with the patient with a thin layer of lead. This paper presents dosimetric investigations in the dose buildup of a collimated 14-MeV DT-neutron beam underneath the surface of a solid phantom behind a 1.0-cm layer of bolus material lined with 0.03 cm of lead. It is shown that most of the dose buildup of the bolus-free neutron beam can be recovered. PMID- 1921893 TI - [Cerebrovascular disorders and administration of oral contraceptives containing gestodene--causal relation or coincidence?]. AB - During the last two years oral contraceptives containing gestodene were suspected to cause cerebrovascular disorders. 52 cases with adverse neurological side effects were registered up to October 31, 1990. Anonymous protocols received from the Companies Schering AG and Wyeth Pharma were analyzed from a clinical point of view. There are different arterial and venous, thrombotic and embolic disorders caused by different pathogenetic principles. Only one third of the cases was documented by neuro-imaging to render possible actual diagnostic reliability. Suspected cases represent a great number of different cerebrovascular disorders usually observed in neurological and neurosurgical series, concerning both men and women, OC-users and non users. PMID- 1921894 TI - [Atrial fibrillation in patients of a medical clinic--a marker for multi morbidity and unfavorable prognosis]. AB - Out of 724 patients admitted to the medical department of a community teaching hospital during three months 110 (14.5%) had electrocardiographically documented atrial fibrillation (AF). 56% had chronic and 44% intermittent AF. Only 66% of patients with AF suffered from diseases generally accepted as cause of AF, 29% had cardiovascular and pulmonary risk factors, 5% had lone AF. AF was already known in 66% of patients, in 21% AF was documented at the first time, only 14% were admitted because of AF, although AF was clearly the cause of symptoms in an additional 11%. The mean age of patients with AF (72 years) was higher than that of patients without AF. 95% of patients with AF suffered from more than one cardiovascular or pulmonary disease or risk factor (mean index of diseases of 3.2). Hospital mortality of patients with AF was much higher than mean total hospital mortality (19 vs 7.7) except in patients with lone AF. We conclude that AF is a marker of multimorbidity and bad prognosis in patients of general internal medicine. PMID- 1921895 TI - [Computer-assisted analysis of wall motion of the right ventricle in a normal patient sample and diagnosis of right heart infarction using transesophageal echocardiography]. AB - Using 2D and M-Mode transesophageal short axis cross sections, right ventricular systolic wall motion was quantified in 15 normal patients. A further group of 39 patients with right ventricular infarction was investigated. In the normal group fractional shortening of the septum was -19.6% (-45 to 8%), that of the lateral wall 51.6% (37 to 73%), of the posterior wall 33.9% (5 to 50%) and of the anterior wall 42.7% (18 to 57%). Right ventricular infarction (RVI) was associated in 33 patients with posterior left ventricular infarction (85%) and in three patients with anterior infarction. In two cases only an isolated RVI was found. Right ventricular dilation occurred in 24 patients (61%). Hemodynamic criteria were fulfilled in eleven out of 21 patients (53%). RVI was confirmed in one patient by surgery and in ten patients by autopsy. Recognition of regional wall motion abnormalities by transesophageal echocardiography permits an accurate bedside identification of RVI. 2D and M-Mode registration of the short axis improves RVI assessment. Wall motion analyses offer the possibility to determine the extent of right ventricular infarction. PMID- 1921896 TI - [Hemodynamic effects of intermittent intra-arterial infusion treatment with prostaglandin E1 in peripheral arterial occlusive disease]. AB - 14 femoral arteries of twelve patients with peripheral arterial occlusive disease (Fontaine stage II: n = 4, stage III/IV: n = 10) were investigated before, immediately after a series of 26 (ten to 52) intraarterial infusions with prostaglandin E1, and 30 weeks later. Using combined B-mode and pulsed Doppler (duplex) ultrasound blood flow measurements were performed in the common femoral, the superficial femoral, and the deep femoral artery. There was a significant decrease of resting blood flow volume in the common femoral artery after therapy (418.5----362.2 [p less than 0.01]----324.5 ml/min [p less than 0.05]) in the group of patients treated successfully. The peak flow (maximum value of blood flow volume during reactive hyperaemia) in the common femoral artery increased significantly after therapy (597.3----779.1 [p less than 0.05]----843.7 ml/min). The increase of peak flow correlated well with clinical improvement. Other parameters (blood flow velocities, pulse rise time, pulse decrease time, pulsatility index) changed without correlation to clinical outcome. The increase of peak flow after therapy might be caused by an improved collateral circulation, and the decrease of resting blood flow might be due to metabolic effects of prostaglandin E1 (improved oxygen utilization). PMID- 1921897 TI - [Clinical significance and molecular principles of chromosome aberrations in malignant lymphoma]. PMID- 1921898 TI - [The limits of intensive care medicine]. PMID- 1921899 TI - [Rare diseases do occur: Haemophilus endocarditis]. PMID- 1921900 TI - [Haemophilus aphrophilus--a rare endocarditis pathogen]. PMID- 1921901 TI - [Indications for splenectomy in splenic vein thrombosis]. PMID- 1921902 TI - [Chronic myelomonocytic leukemia--myelodysplastic syndrome]. PMID- 1921903 TI - [Adrenomyeloneuropathy and adrenoleukodystrophy. Description of a family with neurological and psychiatric syndromes and implication for the differential diagnosis of the paraspastic symptoms]. PMID- 1921904 TI - [Liver involvement as leading symptom of a kappa light-chain deposit disease]. PMID- 1921905 TI - [Hemorrhagic colitis due to Escherichia coli O 157:H7]. PMID- 1921906 TI - [Varicella pneumonia in pregnancy: a life-threatening complication of chickenpox]. PMID- 1921907 TI - [Acute disseminated encephalomyelitis]. PMID- 1921908 TI - [Type II mixed cryoglobulinemia in chronic hepatitis]. PMID- 1921909 TI - [Bronchial carcinoma or Wegener's disease: problems with differential diagnosis and an atypical course]. PMID- 1921910 TI - [Plasma exchange as therapy of recurrent hemolytic-uremic syndrome (HUS) in adults]. PMID- 1921911 TI - [Early stomach carcinoma following a reflux-preventing gastrectomy]. PMID- 1921912 TI - [Focal liver lesions: partial nodular regenerative hyperplasia of the liver]. PMID- 1921913 TI - [Generalized argyria caused by targesin-containing drug used for stomach complaints]. PMID- 1921914 TI - Wernicke's encephalopathy and Korsakoff's psychosis: to fortify or not to fortify? AB - The conventional wisdom suggests that Korsakoff's psychosis, an amnesic disorder associated with prolonged alcohol consumption, is the chronic outcome of a thiamin deficiency first exhibited as Wernicke's encephalopathy. The present paper describes the debate in Australia over whether flour and alcoholic beverages should be fortified with thiamin, in an attempt to prevent Wernicke's encephalopathy and thus Korsakoff's psychosis. We conclude that the scientific evidence linking Wernicke's encephalopathy and Korsakoff's psychosis is tenuous. Certainly, it is not sufficient to support what would amount to mass medication. PMID- 1921915 TI - Effects of prenatal alcohol exposure at school age. I. Physical and cognitive development. AB - Alcohol is a potent teratogen associated with dysmorphology, growth retardation, and neurological damage in children with the full fetal alcohol syndrome (FAS); alcohol is also associated with growth retardation and behavioral alterations in neonates prenatally exposed to various dosages. Questions remain about the long term consequences of prenatal alcohol exposure. This study reports on the follow up of a subsample of 68 children, the majority of whom were low income and black (mean age: 5 years, 10 months) who were first evaluated as neonates. Physical and cognitive outcomes of 25 children of women who drank throughout pregnancy [absolute alcohol (AA)/week: mean = 11.80 oz), even after receiving an educational intervention to stop drinking, were compared with outcomes of children in two contrast groups: a) women (n = 22) who stopped drinking (AA/week: mean = 11.46 oz) in the second trimester after an educational intervention but resumed postpartum; and b) women who did not drink during pregnancy and who drank little postnatally (n = 21). Children were compared for alcohol-related birth defects (ARBDs), growth (height, weight, and head circumference), and cognitive, academic, and adaptive measures. Neonatal and current physical measures were correlated to determine predictability of neonatal status. When the effects of age and gender were controlled, children in the continued-to-drink group showed significantly more ARBDs and had smaller head circumferences than those in the other two groups. When current drinking reported by caretakers was controlled, the children who were exposed throughout pregnancy also showed significant and consistent deficits in several areas of intellectual functioning including sequential processing (short-term memory and encoding) and overall mental processing. Alcohol-exposed children displayed significant deficits in preacademic skills when compared with children of nondrinkers, with both alcohol groups deficient in premath and reading skills. There were no differences in adaptive behavior at follow-up. These data suggest that alcohol exposure throughout pregnancy is correlated with persistent physical differences as well as identifiable deficits in sequential memory processes and specific academic skills. However, even when alcohol use is limited to the first part of pregnancy, significant deficits in academic skills and growth parameters are measurable. PMID- 1921916 TI - Effects of prenatal alcohol exposure at school age. II. Attention and behavior. AB - Alcohol, a potent teratogen, has been suggested as an etiologic agent in attention deficit disorder with hyperactivity (ADHD), which is often diagnosed in children with fetal alcohol syndrome (FAS) and in children of alcoholics. We studied attentional and behavioral factors associated with diagnosis of this disorder in children selected from a predominantly low-income, black population who were tested as part of a longitudinal follow-up of children with prenatal alcohol exposure. Sixty-eight children with a mean age of 5 years 10 months, born to three groups of mothers, were assessed. These groups consisted of: a) women who reported not drinking during pregnancy (n = 21), b) women who reported drinking throughout pregnancy (n = 25), and c) women who reported drinking an equivalent amount but who stopped drinking after educational intervention during the second trimester (n = 22). Dimensions assessed included factors related to attention on a computerized task, impulsivity, and the presence of psychiatrically significant internalizing and externalizing behaviors. In addition, free play and mother-child interactions were video-taped, and evidence of overactive and noncompliant behaviors were noted. Hyperactivity and impulsive behavior were not evident. Results indicated that children exposed throughout pregnancy showed deficits in the ability to sustain attention and were more often described by teachers, although not by their mothers, as showing attentional and behavioral problems. Problems in both internalizing and externalizing behaviors also were noted by teachers. However, when current drinking was controlled, only externalizing behaviors remained different by group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921917 TI - Interactive effects of prenatal alcohol and cocaine exposures on postnatal mortality, development and behavior in the Long-Evans rat. AB - Polydrug abuse has increased substantially in recent years amongst obstetric patients. One of the most common drug combinations is alcohol and cocaine. To better understand the adverse consequences of this drug combination on pregnancy and the offspring, alcohol (2 g/kg, b.i.d.) and cocaine HCl (30 mg/kg, b.i.d.) were administered individually and in combination to separate groups of pregnant Long-Evans rats from gestation days 7-20. The pregnant dams were evaluated for maternal weight gain, food and water consumption, mortality, and gestational length. The offspring were evaluated for physical maturation, mortality, and behavior. The drug combination was found to have greater effects regarding decreased birth weight, increased postnatal mortality, and delayed physical maturation than either drug alone. Drug treatments also influenced activity monitor behavior in that prenatal cocaine exposure was associated with hypoactivity while the alcohol and the alcohol-plus-cocaine treatments were associated with hyperactivity in periweanling pups. Drug treatments had no significant effects on passive or active avoidance behaviors. These results suggest that combining alcohol and cocaine increases the risk to the offspring. PMID- 1921918 TI - A toluene-induced motor syndrome in rats resembling that seen in some human solvent abusers. AB - The purpose of these experiments was to determine the extent to which subchronic exposure of rats to toluene might cause symptoms similar to those seen in some heavy abusers of toluene-containing products. In the first exploratory experiment, weanling male Fischer-344 rats were exposed to air, toluene, n hexane, or a mixture of toluene, n-hexane, and methyl ethyl ketone (8 h per day, 7 days per week) for 11 weeks. A mild peripheral neuropathy was revealed by measures of grip strength in the rats exposed to n-hexane alone or in the mixture, but not in the rats exposed to toluene. Instead, the rats exposed to toluene alone developed a persisting motor syndrome characterized by a shortened and widened gait and a widened landing foot splay. The rats exposed to toluene alone or in the mixture were also hearing impaired, but not the rats exposed to n hexane alone. In the second experiment, done to confirm and extend these results, weanling male Fischer-344 rats were exposed to toluene under three different daily schedules--2,200 ppm continuously for 8 h per day; 4,400 ppm, 30 min each h, 8 h per day; or 6,200 ppm, 15 min each h, 8 h per day. The exposures were 7 days per week for 23 weeks. The motor syndrome and hearing impairment were replicated in all essential respects in all toluene-exposed groups with no appreciable differences attributable to the daily exposure schedules. The effects were still evident 15 weeks after the last exposure. Toluene inhibited weight gain in both experiments, and in the second experiment, it was found that skeletal growth (torso length, rump width) was also inhibited. Toluene did not significantly impair rotorod performance in either experiment or acquisition of a spatial-navigation task in the second experiment. No neuropathologic correlates of the persisting motor syndrome were found in either experiment when the rats were sacrificed 9 and 16 weeks after the last exposure, respectively. These results demonstrate that toluene can cause a persisting motor syndrome in rats that resembles, to some extent at least (i.e., wide-based ataxic gait), the syndrome seen in some heavy abusers of toluene-containing products. PMID- 1921919 TI - Total number and mean cell volume of neocortical neurons in rats exposed to 2,5 hexanedione with and without acetone. AB - The toxicological effects of 2,5-hexanedione (2,5-HD) alone and combined with acetone on the number and size of neurons in the cerebral cortex of rats were evaluated with stereological techniques. Thirty rats were equally divided into three groups: One control, one receiving 0.5% 2,5-HD, and one receiving 0.5% 2,5 HD and 0.5% acetone in the drinking water for seven weeks. Unbiased estimates of the total number of neocortical neurons, as well as the mean neuronal nuclei and cell body volumes were obtained from systematically sampled 3.5-microns sections. The total number of neurons in the 2,5-HD group was significantly smaller than the control group (p less than 0.05, one-tailed t-test). Both test groups showed significant changes in the mean cell body volume: Compared with the control group, animals exposed to 2,5-HD had 11% smaller cell body volumes while animals exposed to 2,5-HD and acetone had 13% larger cell body volumes. These data represent the first unbiased estimation of mean cell volume in toxicology. We propose the nucleator method as an efficient and accurate tool for estimating quantitative changes in toxicological research. PMID- 1921920 TI - Effects of 2,5-hexanedione alone and in combination with acetone on radial arm maze behavior, the "brain-swelling" reaction and synaptosomal functions. AB - A multidisciplinary study to investigate 2,5-hexanedione (2,5-HD)-induced CNS neurotoxicity and its proposed potentiation by acetone (AC) was conducted. Neurobehavioral testing, estimation of the brain-swelling reaction, neuropathological and morphometric measurements as well as synaptosomal 5 hydroxytryptamine (5-HT) uptake were evaluated. Male Wistar rats were exposed through their drinking water, for seven weeks, either to 0.5% 2,5-HD alone or to 0.5% 2,5-HD in combination with 0.5% AC. This 2,5-HD dose is known to cause neurotoxicity in the peripheral nervous system. Exposed animals were compared to a control group that received tap water. Acquisition but not performance of spatial learning, as measured in the radial 8-arm maze, was significantly inhibited by the coexposure to 2,5-HD and AC. Brain weights of rats exposed to 2,5-HD alone and to 2,5-HD and AC in combination, were slightly, albeit significantly, reduced. Synaptosomal high-affinity 5-HT uptake rate and uptake capacity were significantly reduced by 2,5-HD alone and in combination with AC. The morphometric results are reported in a companion paper. In conclusion, the present findings indicate that 2,5-HD is a CNS-neurotoxicant. The hypothesis about AC potentiation of 2,5-HD CNS-neurotoxicity was supported. PMID- 1921921 TI - Prenatal and preschool age lead exposure: relationship with size. AB - This report examines possible adverse effects on size and growth associated with subclinical prenatal and preschool age lead exposure in an urban cohort followed prospectively from birth through early childhood. Measurements of weight, stature (length), and head circumference were obtained at birth and during five subsequent in-home assessments. Prenatal lead exposure was assessed by cord (n = 185) and maternal (n = 162) blood lead levels at delivery. Preschool blood lead samples were obtained at ages six months (n = 151), two years (n = 165), three years (n = 165), and four years, ten months (n = 164). Multivariate longitudinal analyses incorporating adjustment for covariates revealed no statistically significant adverse effects of prenatal lead exposure on either neonatal size or on subsequent growth through age four years, ten months. Similarly, no statistically significant adverse effects were found between the preschool lead indices derived from blood collected at or after age two years and ensuing size measurements. We also found no evidence for an interaction between pre- and postnatal lead exposure. A marginal inverse association was exhibited between blood lead at six months and subsequent measures of head circumference. Limitations in the implications of this result in the context of many nonsignificant tests were discussed. PMID- 1921922 TI - Lead exposure and diet: differential effects on social development in the rhesus monkey. AB - Infant rhesus monkeys ingested 0 or 1.0 mg/kg lead acetate daily from birth to one year postpartum in dietary milk. Half the monkeys in each group were offered milk ad lib, and half were given restricted quantities. Chow was available ad lib to all monkeys. Groups of 4 monkeys interacted for 1.5 h/day, 5 days/week beginning at approximately 2 months of age. The social sessions were moved to a larger arena at about 9 months postpartum. Ongoing behavior was observed during social sessions twice weekly beginning at about 3 months of age for 28 weeks, and again beginning at about 16 months of age for 11 weeks. Play behaviors were particularly susceptible to lead; social play was more severely disrupted than nonsocial play. Lead suppressed play in both test environments during the first year postpartum while self-stimulation and fearful behaviors increased. Lead associated alterations in behavior were still present several months following termination of lead intake. Restriction of milk resulted in increased chow consumption but had little impact on behavior. Effects of lead may have been more profound in monkeys maintained on the restricted milk diet than in monkeys given milk ad lib. PMID- 1921923 TI - Caffeine use during pregnancy and child outcome: a 7-year prospective study. AB - Caffeine (from coffee, tea, cola, and/or chocolate) was the most frequently ingested drug among 1529 pregnant women interviewed in 1974-75. Linear and threshold effects of prenatal caffeine on pregnancy outcome and offspring development were examined in a cohort of approximately 500 offspring. After appropriate statistical adjustment for relevant covariates (cigarette smoking, alcohol, maternal size, demographics, etc.) prenatal caffeine exposure was not related to most newborn and infant outcome measures, including height, weight or head circumference, or to individually administered IQ and attention tests at 7 years of age. Only one isolated dependent variable of the many was significantly associated with prenatal caffeine exposure: namely breech presentation. However, since this report involved a secondary analysis of data gathered for other purposes, specifically designed studies would be required to determine the validity of the observed association for any particular variable. The general conclusion is that the long-term consequences of prenatal caffeine in this cohort are null. PMID- 1921924 TI - Reward reductions found more aversive by rats fed environmentally contaminated salmon. AB - Pacific salmon stocked in Lake Ontario concentrate persistent toxic chemicals such as PCBs, DDT, DDE, mercury and dioxin. The present experiments support earlier findings that consumption of these salmon by laboratory rats increases their behavioral reactions to negative events. For 20 days rats were fed a diet consisting of 30% Lake Ontario salmon or a control diet of Pacific Ocean salmon or no salmon. They were then trained to run down an alley to receive a large 15 pellet or small 1-pellet food reward (6 trials/day). Following 72 trials the 15 pellet groups were shifted to 1 pellet for 90 trials, and showed a contrast (depression) effect: they ran more slowly than the groups always given 1 pellet. Rats previously fed Lake Ontario salmon showed a much larger contrast effect than the two control groups. These results were replicated in a second experiment, and a group fed a 10% diet of Lake Ontario salmon for 60 days showed the same size contrast effect as the group fed a 30% diet for 20 days. PMID- 1921925 TI - Maternal and neonatal effects of moderate cocaine use during pregnancy. AB - Thirty-four women who reported using cocaine during pregnancy were compared to 600 women who reported no cocaine use during pregnancy and none for the year prior to pregnancy. Subjects were participants in a prospective, longitudinal study of prenatal substance use. The sample consisted of young, predominantly single, low-income women attending a public prenatal clinic. Women were interviewed at the end of their first, second and third trimesters regarding cocaine, alcohol, marijuana, tobacco and other drug use. The majority of the cocaine users were light to moderate users who decreased their use during pregnancy. The cocaine group was more likely to be white and to use alcohol, marijuana, tobacco and other illicit drugs more heavily than the comparison group. The cocaine users had more previous fetal losses but did not differ on other obstetrical complications. Infant growth, morphology and behavior were not affected. PMID- 1921926 TI - Neurobehavioral toxicology of halothane in rats. AB - Halothane, a commonly used general anesthetic, is considered to be relatively safe for that purpose. Chronic exposure, however, has been found to cause long lasting damage to neural structure and impairment of behavioral function. In rats, behavioral alterations are particularly evident after developmental exposure, but they can also be seen with adult exposure, especially when halothane is given during the period of neural regrowth following a brain lesion. The pattern of neural damage includes retarded synaptogenesis, impaired dendritic branching and disruption of organelle structure. The behavioral syndrome includes learning impairment, decreased exploratory behavior and decreased nociceptive reactivity. In general, the neural pathology is more pronounced and more easily discernible than the behavioral effects. Neural damage, particularly to the hippocampus, can be clearly seen at points when behavioral impairments have not been found. This demonstrates that in some cases changes in neural structure can be more sensitive indicators of toxic damage than behavioral dysfunction. Halothane exposure has proved to be quite useful as an experimental tool in the study of neural and behavioral recovery after brain lesions. For example, after unilateral entorhinal cortical lesions, behavioral recovery and reactive synaptogenesis occur contemporaneously. It has not been demonstrated whether the behavioral recovery is due to this reinnervation. Postlesion halothane exposure almost completely suppresses reactive synaptogenesis, however, behavioral recovery of T-maze alternation behavior occurs in the halothane-treated rats as well as in controls. This suggests that recovery of spatial performance after such a lesion is not due to recovery of innervation in the dentate, but to some other process such as other neural systems taking over the functions lost with the brain lesion. The studies reviewed highlight the dangers of halothane exposure, especially during development or when recovering from brain injury. They also provide a good case study for comparing the relative sensitivity of morphological and behavioral measures in toxicology and point to the potential use of halothane as an experimental tool for examining the relationships between neural structure and behavioral function. PMID- 1921927 TI - Prenatal valproic acid exposure decreases neuronal membrane order in rat offspring hippocampus and cortex. AB - Sprague-Dawley rats were administered 0 or 200 mg/kg of valproic acid (VPA) on days 7-18 of gestation. Controls were pair-fed. On postnatal day 28, analyses of brain tissues were performed on enriched neuronal membrane fractions from cerebellum, hippocampus, and cortex for anisotropy using the membrane probe 1,6 diphenyl-1,3,5-hexatriene (DPH). No significant differences in membrane anisotropy were noted in the cerebellum, but a significant reduction in anisotropy in the hippocampus and cortex was observed. This change corresponds to a 3-5 degrees C increase in temperature or that produced by other membrane disordering agents (ethanol, phenytoin). An association between membrane anisotropy and functional effects of prenatal VPA exposure is discussed. PMID- 1921928 TI - Depression. Having it made me see. PMID- 1921929 TI - Out from the shadow of Tuskegee. Fighting racism in medicine. PMID- 1921930 TI - Incidentally discovered adrenal masses. AB - This report describes a retrospective study of 23 patients with incidentally discovered adrenal masses. Two patients with subclinical cortisol secretion developed adrenal insufficiency after removal of benign adenomas. Another patient, who probably harbors an asymptomatic pheochromocytoma, developed a hypertensive crisis when a mass was palpated during aortic vascular surgery. Twelve patients underwent surgery. Seven benign adenomas, an angiomyolipoma, and a cyst were removed. Three patients had malignant masses that include an angiosarcoma, an adrenal adenocarcinoma, and a congenital neuroblastoma. We conclude that hormones, especially cortisol, may be secreted in subclinical amounts by incidentally discovered masses. We recommend a concise laboratory evaluation that includes an overnight dexamethasone suppression test. Based on our interpretation of the literature, we believe masses greater than 3 cm in size should be removed. Patients who do not undergo surgery should have computed tomographic scans repeated for one year and should be reassessed periodically for the development of hormone secretion. PMID- 1921931 TI - Professional peer review. Precautions for physicians. PMID- 1921932 TI - A management perspective on medical group mergers. PMID- 1921933 TI - Payment reform takes a turn for the worse. PMID- 1921934 TI - AIDS award to former state doc. PMID- 1921935 TI - Measles, immunizations, and vaccines. PMID- 1921936 TI - Zumbro Valley on HIV in health care settings. PMID- 1921937 TI - Transforming the American Red Cross. PMID- 1921938 TI - [Changes in movement-related cortical potentials in Parkinson's patients before and after treatment with levodopa]. AB - Cortical potentials associated with voluntary, self-paced wrist flexion (MRPs) were recorded from 3 scalp locations (Cz and psi contralateral hand motor area) in patients with Parkinson's disease (9 de novo patients and 30 L-Dopa treated patients). The analysis concerned 3 components of the MRPs: the 2 slow negative shifts (NS1 and N1) before the movement onset and the motor potential (MP). The NSI amplitude was measured at Cz, the peak negativity N1 and MP from contralateral hand motor area location. The potential distribution was also studied. The amplitude of the MRPs components was the same as in the normals. But in de novo patients, the potential distribution of the NS1 component was different; a Cz preponderance of the NS1 amplitude was not found. In patients treated with L-Dopa, there is a negative correlation between the changes in amplitude and the changes in clinical rating for NS1, N1 and MP components. The decrease in the MRPs components was significant from stage III and IV of the Hoehn and Yahr scales. After L-Dopa therapy, the NS1 component from de novo patients was increased in amplitude. The amplitude of the MRPs components from patients with L-Dopa induced clinical fluctuations was reduced during "off" period in comparison to "on" period. The findings suggest that the NS1 potential and the N1 and MP components share 2 distinct systems for the control of voluntary movement. Their mechanism in Parkinson's disease is discussed. PMID- 1921939 TI - [Cerebral anoxia in near-drowning of children. The prognostic value of EEG]. AB - The retrospective electroclinical evaluation of anoxia by near-drowning in 23 children observed between 1985 and 1989 revealed 2 groups, each with a distinct evolution: the first group, with good prognosis of 17 children, which recovered consciousness without neurological complications between 2 d and 1 wk after the accident. The second group of 6 children with a poor outcome--either i), death; or ii), state of permanent injury; or iii), a high level of clinical deficits. The gravity of the early clinical state, the estimated duration of cardiorespiratory arrest, the severity of the hypothermia, the seizures and the paroxysmic activity, do not determine the severity of near-drowning encephalopathy. The EEG patterns described in correlation with the group and the clinical outcome permitted determination of prognostic criteria. A good prognostic consisted of the following: moderate background activity, sleep patterns, response to auditory and painful stimulations, and numerous beta rhythms. A bad outcome was defined by: high voltage, rhythmic delta waves; biphasic sharp waves; monotonous EEG, "burst-suppression" pattern, absence of beta rhythms. The importance of EEG recordings is emphasized performed as early as possible and until 3 or 7 d after the near-drowning. Any modification in the EEG, with attenuation or disappearance of fast frequencies and painful reactivity, appearance or enhancement of slow and biphasic sharp waves, are ominous signs and may be accompanied by the appearance of cerebral oedema and decerebration. PMID- 1921940 TI - [Diurnal variations of the composition of cognitive evoked potentials]. AB - Auditory evoked potentials are recorded in 12 subjects 4 times per day: 08 30, 11 30, 14 30 and 18 30. The daily variations of N1, P2, N2 and P3 are studied globally and according to the (morning- or evening) type of subjects. The latency of N2 decreases during the day; it possibly reflects variations in vigilance. The P3 amplitude varies according to the subject typology: for morning-type subjects, P3 is higher in the afternoon than in the morning, and for evening-type subjects, P3 decreases from morning to evening. These evolutions possibly reflect the effort in attention required by different tasks. PMID- 1921941 TI - [Alpha coma: rectrospective presentation of 20 cases]. AB - Alpha coma is a relatively rare variety of EEG resulting from diffuse cerebral anoxia, focal brainstem lesions, metabolic disturbances or intoxications. It is a monotonous, unreactive and anteriorly predominant activity of less than 50 microV and of 8 to 13 Hz. Twenty cases of alpha coma are reported: 16 resulting from anoxic encephalopathy, 2 from brain stem strokes, and 2 from metabolic encephalopathy. Cardiac arrest was the main cause of alpha coma (10 cases); a large number of patients (7 cases) died, or have survived with severe neurologic deficits (2 cases). In 2 cases there was a metabolic-toxic cause (benzodiazepines and parathion intoxication). The 2 patients with pontomesencephalic haemorrhage died. The physiopathogenicity of alpha coma, which remains obscure, is also discussed. PMID- 1921942 TI - [Trigeminal somatosensory evoked potentials in workers handling trichloroethylene]. AB - Trigeminal somatosensory evoked potentials (TSEP) were studied in 33 workers manipulating trichlorethylene for 3 to 22 years and in 33 control subjects. A significant excessive latency delay of N13, P17 and N45 waves in workers was found. Evoked potential abnormalities found in 15 exposed subjects (45%) were as following: excessive latency delay in 9 cases (27%), decrease of amplitude in 2 cases (6%) and asymmetrical responses in 4 cases (12%). Among 5 workers (15%) presenting clinical abnormalities of trigeminal nerve impairment, only one had normal evoked potential. TSEP were altered in 11 workers (33%) who had no clinical impairment. We suggest that TSEP should be confirm trigeminal impairment in chronic cases of workers exposed to carbon tetrachloride and to predict infraclinic lesions. PMID- 1921943 TI - Clinical anatomy of the spinal cord. AB - To properly diagnose and manage, spinal cord disease, it is necessary first to understand anatomic organization. This article discusses the external morphology and blood supply of the spinal cord, its internal neuronal organization, and several anatomofunctional correlations. PMID- 1921944 TI - Disorders of the spinal cord. PMID- 1921945 TI - Aspects of spinal cord structure and reflex function. AB - Current textbooks still feature overly simplistic approaches to spinal cord function. Medical training still emphasizes the notion of stereotyped spinal reflex responses fixed by rigid neuronal connections. These assumptions must be replaced by recognizing (1) that descending and sensory information converges on the same sets of interneurons, (2) that the effects of different classes of afferents from muscle, joints, and skin act together in different combinations as a result of convergence, (3) that the flexibility of reflex responses is determined in large measure by the excitability of interneurons, (4) that conventional and monoamine transmitters act and interact to adjust neuronal excitability and transmission in reflex pathways, and finally (5) that rhythmic movements are largely determined by intraspinal circuitry. PMID- 1921946 TI - Neuropathology of the spinal cord. AB - The neuropathology of the spinal cord is described and illustrated from the viewpoint of a neuropathologist observing at necropsy the many traumas and pathologic diseases affecting the spinal cord. The article provides the clinician with an insight into the disease processes and anatomic derangements underlying the neurologic deficits in paraplegia and quadriplegia. Today, the clinical examination of patients with spinal cord trauma or spinal cord disease is greatly assisted by many anciliary investigations, notably, radiology and the newer imaging techniques now applied to successfully to the spinal cord. Comparison of the patient's neuropathology with the classical neurophathology of the spinal cord, provided in this article, remains important for the clinician. PMID- 1921947 TI - The clinical diagnosis of disorders of the spinal cord. AB - Disease of the spinal cord or cauda equina may cause pain, motor abnormalities, sensory disturbance, alteration of reflexes and muscle tone, and bladder dysfunction. These five neurologic abnormalities occur in various combinations, evolve rapidly or slowly, and result in one of eight possible spinal cord syndromes. When a particular syndrome is defined by neurologic history and examination, differential diagnosis is limited to only a few possible disorders. An appropriate neuroradiologic or electrophysiologic procedure done at this point will usually provide the correct diagnosis. PMID- 1921948 TI - Acute nontraumatic myelopathies. AB - Acute myelopathies (acute transverse myelopathies) can be divided into two major groups. Vascular myelopathies are caused by aortic disease, surgery, or intrinsic vascular disease of cord vessels. Inflammatory/demyelinative myelopathies include lupus erythematosus, various viral infections, and primary demyelinating disease. Criteria for diagnostic decisions and recent data from magnetic resonance imaging are reviewed. PMID- 1921949 TI - Chronic nontraumatic diseases of the spinal cord. AB - This article reviews common chronic diseases of the spinal cord such as spinal multiple sclerosis, cervical spondylosis, and motor system diseases, including amyotrophic lateral sclerosis. Secondary epidural and meningeal tumors and syringomyelia are also discussed. PMID- 1921950 TI - Spinal cord injury. AB - The evaluation and treatment of spinal cord injury continues to evolve, enhanced by new imaging modalities. Their application in reference to the cervical, thoracic, and lumbar spine is discussed. Treatment options, both conservative and surgical, are outlined. PMID- 1921951 TI - Segmentally specific somatosensory evoked potentials. AB - The recording of segmentally specific somatosensory evoked potentials (SEPs) is time-consuming and the findings have generally been clinically unhelpful. This article critically evaluates the role of these SEPs in patients with disorders of the spinal cord or nerve roots. PMID- 1921952 TI - Clinical neurophysiology of focal spinal cord injury. AB - A focal spinal cord injury produces a host of electrophysiologic abnormalities, most of which reflect either local spinal cord destruction or the functional disconnection of rostral and caudal portions. Routine electromyographic and nerve conduction studies are most useful to investigate the deficits that result from local cord damage and have demonstrated that the injury zone most often extends at least 3 to 4 myotomes. Electromyographic studies of muscles innervated by more caudal myotomes have also shown abnormalities, but the extent to which these reflect primary changes of spinal cord injury is uncertain. Electrophysiologic studies of spinal cord function caudal to the site of injury have shown alterations in autonomic output, as well as changes in the level of excitability of reflex pathways. These changes may provide insight into the mechanisms that underlie the development of spasticity. PMID- 1921953 TI - Neuroimaging of the spinal cord. AB - Neuroimaging of the spinal cord has taken on new dimensions in the past few years. With improvement in surface coils, elimination of artifacts, and fast scan imaging, myelography with all of its complications is on the wane. Computerized tomography is excellent for bony abnormalities, but most patients with spinal disease can be diagnosed with magnetic resonance imaging due to its excellent contrast, spatial resolution, and ability to actually see the spinal cord. However, at times CT is extremely helpful. This article reviews neuroimaging of the major diseases affecting the spine. PMID- 1921954 TI - Rehabilitation of patients with spinal cord disease. AB - Spinal cord injury and disease have multisystem consequences and many potential medical complications. This article addresses the various medical, psychosocial, and vocational issues associated with spinal cord injury and describes how the patient's lifestyle may be affected. The role of the physician and other rehabilitation professionals in the rehabilitation process is described. In addition, various medical concerns, complications, and available treatment modalities are discussed. PMID- 1921955 TI - Disorders of bladder function in spinal cord disease. AB - Successful management of bladder function mandates a thorough knowledge of the neuroanatomy and physiology of micturition. Accurate urodynamic diagnosis of the exact vesicourethral dysfunction is a key to successful management. The primary concern for the urologist is preservation of renal function, taking into account the social needs of the patient. PMID- 1921956 TI - Neurogenic urinary tract infection. AB - Even though renal failure secondary to the urologic complications of chronic or recurrent urinary tract infection has decreased markedly due to advances in diagnostic, preventive, and therapeutic measures, infection and its sequelae continue to be major problems in patients with spinal cord injury regardless of the bladder emptying method employed. Although lower urinary tract complications have decreased with intermittent catheterization, the effects of increased intravesicular pressure, inflammation, and chronic bacterial colonization or invasion of the urinary tract on long-term renal function are still undetermined. Thorough evaluation of the urologic status on a regular basis in all patients with spinal cord injury is encouraged. Treatment of urinary tract infection should be guided by scientific data and drug susceptibilities of etiologic bacteria. The general consensus is that the presence of asymptomatic bacteriuria, particularly in the absence of pyuria, usually does not warrant antibiotic treatment, and that prophylaxis or suppression of infection with systemic antibiotics is not effective for any considerable length of time. Preservation of renal function is the ultimate goal of all bladder management strategies. PMID- 1921957 TI - Disturbed sexual function in patients with spinal cord disease. AB - The normal neural pathways involved in erection and ejaculation and the various spinal cord and central nervous system disorders that can adversely affect these functions are reviewed in this article. Also outlined are treatment strategies currently being employed. PMID- 1921958 TI - Medical complications of spinal cord disease. AB - Spinal cord injury increases the risk of many life-threatening medical problems, including respiratory failure, pulmonary embolism, and renal failure. Respiratory failure results from paralysis of muscles of inspiration (which impairs oxygen transport to alveoli) and of expiration (which impairs cough and predisposes to pneumonia and atelectasis). Respiratory failure in patients with spinal cord injury can be prevented by proper positioning of the patient, training of ventilatory muscles, pulmonary toilet, and aggressive use of antibiotics and bronchodilators. When respiratory failure occurs, it can be managed by administration of oxygen, intubation, and mechanical ventilation, and in instances of paralysis of the diaphragm, by diaphragmatic pacing. The risk of deep vein thrombosis and pulmonary embolism in acute spinal cord disease is increased by the immobilization of the patient and abnormalities in clotting factors. Thrombotic disease in spinal cord disease can be prevented by intermittent calf compression and heparinization. If pulmonary embolism develops, the patient should be started on a regimen of warfarin for at least 3 months. If anticoagulation is contraindicated, a Greenfield filter can be placed. However, concurrent use of quad cough places the patient at increased risk for complications from the Greenfield filter. Chronic pyelonephritis and systemic amyloidosis are the most common causes of renal failure in the patient with spinal cord disease. Renal failure can be prevented by maintaining a low postvoid residual volume, avoidance of indwelling catheters, use of medications that are not nephrotoxic, and rapid treatment of infection. Hemodialysis and peritoneal dialysis can extend the life of the patient with spinal cord disease in whom renal failure develops, and successful use of renal transplantation has recently been reported. PMID- 1921959 TI - The cause, prevention, and treatment of pressure sores. AB - Pressure sores are a common, expensive, and preventable complication of paralysis. They are the result of ischemia produced when tissue is compressed and distorted by pressure exerted between a bone and an external hard surface for an extended period of time. Prevention involves control of the two variables of pressure and time. Pressure can be minimized by using various pressure-reductive devices in the form of mattresses and cushions. Control of time involves scheduled position changes. If pressure sores occur, treatment consists of keeping the sore completely pressure free and clean. Grades I and II sores usually need no further treatment. Grades III and IV sores heal faster and more effectively when treated surgically. PMID- 1921960 TI - Profile of Missouri RNs. PMID- 1921961 TI - Weapon-carrying among high school students--United States, 1990. AB - From 1980 through 1989, more than 11,000 persons died in the United States as a result of homicides committed by high school-aged youth using firearms, cutting instruments, or blunt objects (Federal Bureau of Investigation, Uniform Crime Reports, Supplementary Homicide Report Files, unpublished data, 1980-1989). Firearm-related homicides accounted for more than 65% of these fatalities. Immediate access to a potentially lethal weapon, especially a firearm, may increase the likelihood that a lethal event would result from a violent altercation. This article presents the prevalence and incidence of self-reported weapon-carrying among high school students in grades 9-12 in the United States during 1990. PMID- 1921962 TI - Injuries from motor-vehicle collisions with deer--Kentucky, 1987-1989. AB - Motor-vehicle collisions involving animals can result in both personal injury and property damage. In the United States, deer are a common hazard to motor vehicles and their occupants (1). This report, based on police records submitted to the Kentucky Transportation Cabinet from 1987 through 1989, characterizes motor vehicle collisions with deer in Kentucky. PMID- 1921963 TI - Cigarette smoking among reproductive-aged women--Behavioral Risk Factor Surveillance System, 1989. AB - Women who smoke cigarettes are at increased risk not only for chronic diseases (e.g., lung cancer and chronic obstructive pulmonary disease) but--if they use oral contraceptives--also for myocardial infarction (1). In addition, cigarette smoking during pregnancy increases the risk for low birth weight and premature infants, miscarriage, stillbirth, sudden infant death syndrome, and infant mortality (2). Because of these risks and other health problems associated with cigarette smoking, one of the national health objectives for the year 2000 is to reduce the prevalence of smoking to 12% among reproductive-aged women (18-44 years of age) (3). This report summarizes data from the 1989 Behavioral Risk Factor Surveillance System (BRFSS) on the prevalence of smoking among reproductive-aged women. PMID- 1921964 TI - Unintended pregnancy--New York, 1988-1989. AB - Unintended pregnancies may be associated with an increased occurrence of low birth weight infants and other problems (1). To assist in the prevention of unintended pregnancies, in 1988-1989 the New York State Family Planning Program (NYSFPP) surveyed reproductive-aged women (15-44 years of age) in New York to estimate family planning needs (2). This report presents the results from that survey regarding unintended pregnancy. PMID- 1921965 TI - Lower extremity amputations among persons with diabetes mellitus--Washington, 1988. AB - Diabetes mellitus is the leading cause of lower extremity amputations (LEAs) in the United States, accounting for approximately 50% of all nontraumatic LEAs. To assist public health programs in preventing diabetes-related LEAs in Washington state, the diabetes-control program of the Washington Department of Health characterizes LEAs. This report summarizes an analysis of the incidence of LEAs during 1988 among Washington residents with and without diabetes. PMID- 1921966 TI - Sensitivity of death certificate data for monitoring diabetes mortality--diabetic eye disease follow-up study, 1985-1990. AB - Although death certificates are a primary source of data for characterizing mortality patterns in the United States, the underreporting of diabetes as a cause of death limit the use of death certificates for monitoring diabetes mortality. To determine whether diabetes was underreported on the death certificates of patients with known diabetic eye disease, CDC analyzed data from death certificates for persons identified as deceased by the Diabetic Eye Disease Follow-Up Study (DEDFUS). PMID- 1921967 TI - Body-weight perceptions and selected weight-management goals and practices of high school students--United States, 1990. AB - Among adults, overweight is associated with elevated serum cholesterol levels, elevated blood pressure, and noninsulin-dependent diabetes and is an independent risk factor for coronary heart disease. Youth who are overweight and remain overweight as adults may increase their risk for certain chronic diseases in adulthood. However, overemphasis on thinness during adolescence may contribute to potentially harmful weight-management practices and eating disorders such as anorexia nervosa and bulimia nervosa. This report presents self-reported body weight perceptions and selected weight-management goals and practices among high school students in the United States. PMID- 1921968 TI - Studies on the alteration of chromosome copy number and cell division potential in a dnaA mutant of Escherichia coli. AB - The dnaA167 mutant of Escherichia coli, N167, maintains, on the average, two replicating chromosomes per cell at the permissive growth temperature of 30 degrees C and only one per cell at the higher permissive growth temperature of 38 degrees C. When the growth temperature of this mutant is changed from 30 degrees to 38 degrees C the cells rapidly readjust their chromosome copy number from two to one. I have examined the kinetics of this transition with reference to DNA replication and cell division. My results indicate that this mutant uncouples cell division from chromosome duplication to achieve the appropriate copy number, suggesting that the dnaA gene product may be involved in the coordination between these two cellular events. PMID- 1921969 TI - The tobacco transcription activator TGA1a binds to a sequence in the 5' upstream region of a gene encoding a TGA1a-related protein. AB - We have isolated and characterized a tobacco gene, designated G13, encoding a leucine zipper DNA-binding protein related to the transcription activator TGA1a. The G13 coding region is divided into eight exons and the amino acid sequence of the encoded protein (PG13) shows 76% homology to TGA1a. Their putative DNA contacting regions (basic domains) are identical and they both bind to the same target sequences in vitro. By contrast, some differences are apparent between these proteins at the carboxyl end of the dimerization region (leucine zipper). The basic and leucine zipper domains are encoded on separate small exons. Analysis by DNAse I footprinting, gel shift and competition experiments revealed that TGA1a and PG13 synthesized in Escherichia coli, and the tobacco nuclear factor ASF-1 all bind to at least one site in the 5' upstream region of G13. The presence of a TGA1a binding site in the upstream region of a TGA1a-related gene suggests that transcription of this gene is autoregulated. PMID- 1921970 TI - Catabolite repression of the operon for xylose utilization from Bacillus subtilis W23 is mediated at the level of transcription and depends on a cis site in the xylA reading frame. AB - The Bacillus subtilis xyl operon encoding enzymes for xylose utilization is repressed in the absence of xylose and in the presence of glucose. Transcriptional fusions of spoVG-lacZ to this operon show regulation of beta galactosidase expression by glucose, indicating that glucose repression operates at the level of transcription. A similar result is obtained when glucose is replaced by glycerol, thus defining a general catabolite repression mechanism. A deletion of xylR, which encodes the xylose-sensitive repressor of the operon, does not affect glucose repression. The cis element mediating glucose repression was identified by Bal31 deletion analysis. It is confined to a 34 bp segment located at position +125 downstream of the xyl promoter in the coding sequence for xylose isomerase. Cloning of this segment in the opposite orientation leads to reduced catabolite repression. The homology of this element to various proposed consensus sequences for catabolite repression in B. subtilis is discussed. PMID- 1921971 TI - Mutational specificity of ethyl methanesulfonate in excision-repair-proficient and -deficient strains of Drosophila melanogaster. AB - The vermilion gene was used as a target to determine the mutational specificity of ethyl methanesulfonate (EMS) in germ cells of Drosophila melanogaster. To study the impact of DNA repair on the type of mutations induced, both excision repair-proficient (exr+) and excision-repair-deficient (exr-) strains were used for the isolation of mutant flies. In all, 28 mutants from the exr+ strain and 24 from the exr- strain, were characterized by sequence analysis. In two mutants obtained from the exr+ strain, small deletions were observed. All other mutations were caused by single base-pair changes. In two mutants double base-pair substitutions had occurred. Of the mutations induced in the exr+ strain, 22 (76%) were GC----AT transitions, 3 (10%) AT----TA transversions, 2 (6%) GC----TA transversions and 2 (6%) were deletions. As in other systems, the mutation spectrum of EMS in Drosophila is dominated by GC----AT transitions. Of the mutations in an exr- background, 12 (48%) were GC----TA transitions, 7 (28%) AT-- -TA transversions, 5 (20%) GC----TA transversions and 1 (4%) was a AT----GC transition. The significant increase in the contribution of transversion mutations obtained in the absence of an active maternal excision-repair mechanism, clearly indicates efficient repair of N-alkyl adducts (7-ethyl guanine and 3-ethyl adenine) by the excision-repair system in Drosophila germ cells. PMID- 1921972 TI - Analysis of a ribosomal RNA methylase gene from Streptomyces tenebrarius which confers resistance to gentamicin. AB - Resistance to the aminoglycoside gentamicin in the nebramycin producer, Streptomyces tenebrarius, occurs at the level of the ribosome. A resistance determinant isolated from this actinomycete was previously shown to encode a methylase enzyme which modifies residue G-1405 of 16S ribosomal RNA. This gene (kgmB) has been sequenced and expressed in Escherichia coli using lacZ transcriptional signals since, like many other actinomycete genes, kgmB is not expressed in E. coli from its own promoter. The 5' end of the kgmB transcript has been mapped revealing a single promoter which does not obviously conform to the prokaryotic consensus. PMID- 1921973 TI - A 2.6 kb intron separates the signal peptide coding sequence of an anther specific protein from the rest of the gene in sunflower. AB - We have isolated and sequenced an anther-specific gene from sunflower which encodes an 800-nucleotide transcript detectable in the peripheral anther cells. It contains an intron of 2615 bp, which separates the first exon (77 bp) coding for a putative signal peptide of 21 amino acids, from the second exon (563 bp) coding for a 100 amino acid polypeptide. The 5' and 3' untranslated regions comprise respectively 13 and 264 bp. The SF2 gene is present in the sunflower genome in several copies, all or most of which contain a closely related intron. PMID- 1921974 TI - The Oenothera plastome mutator: effect of UV irradiation and nitroso-methyl urea on mutation frequencies. AB - Oenothera plants homozygous for a recessive plastome mutator allele (pm) showed spontaneous mutation frequencies for plastome genes that are 200-fold higher than spontaneous levels. Mutations occurred at high frequencies in plants grown in the field, in a glasshouse, or as leaf tip cultures under fluorescent light, indicating that the plastome mutator activity is UV-independent. However, the chlorotic sectors became visible at an earlier stage of development when seedlings were irradiated, compared to seedlings that were not exposed to UV. These results imply that the rate of sorting-out was increased by the irradiation treatment, possibly due to a decrease in the effective number of multiplication competent plastids, or a reduction in the extent of cytoplasmic mixing. Nitroso methyl urea treatment of seeds had a dramatic effect on mutation frequency in both wild-type and plastome mutator samples. When the background mutation rates were low, the combination of the plastome mutator nucleus and the chemical mutagenesis treatment resulted in a synergistic effect, suggesting that the plastome mutator may involve a cpDNA repair pathway. PMID- 1921975 TI - Gene conversions within the Cup1r region from heterologous crosses in Saccharomyces cerevisiae. AB - Meiotic recombination among unselected tetrads was analyzed genetically and physically in a heterologous cross where one parent carried six copies of a 1.6 kb CUP1 repeat while the other parent carried seven copies of a 1.1 kb repeat. In the heterologous cross, 140 unselected, complete tetrads were subjected to Southern analysis and 20% exhibited meiotic copy number alterations at the CUP1 locus. Most events, more than 75%, involved only a single spore of a tetrad, and were largely intrachromosomal or sister chromatid events. However, some conversions and associated crossovers between homologs were also observed. We propose that the high level of heterologies interferes with homologous exchanges and leads to an increase in intrachromosomal events. PMID- 1921976 TI - Pulsed field gel electrophoresis reveals chromosome length differences between strains of Cladosporium fulvum (syn. Fulvia fulva). AB - Methods are described for the electrophoretic separation of chromosome-sized DNA molecules from the fungal tomato pathogen Cladosporium fulvum (syn. Fulvia fulva). Using a hexagonal electrode array and switching times of 75 min at 45 V for 14 days, nine bands could be resolved. By comparison with co-electrophoresed Aspergillus nidulans chromosomal DNA (which was resolved into seven bands), the sizes of the C. fulvum bands are estimated to be between 1.9 Mb and 5.4 Mb. The two largest bands are believed to be doublets, giving a minimum genome size of 44 Mb. Cloned probes for the ribosomal DNA repeat, an anonymous single copy fragment and a newly discovered retrotransposon were hybridized to blots of the pulsed field gels, demonstrating the use of this technique for genomic mapping. Most strains of C. fulvum had an identical pattern of bands. Two strains exhibited two polymorphisms which could be due to a translocation. PMID- 1921977 TI - Conservation of xcp genes, involved in the two-step protein secretion process, in different Pseudomonas species and other gram-negative bacteria. AB - The two-step protein secretion pathway in Pseudomonas aeruginosa is dependent on the xcp genes. We investigated whether a similar secretion mechanism is present in non-pathogenic Pseudomonas spp. and in other gram-negative bacteria. The plant growth stimulating Pseudomonas strains P. putida WCS358, P. fluorescens WCS374 and Pseudomonas B10 appeared to secrete proteins into the extracellular medium. Southern hybridization experiments showed the presence of xcp genes in these strains and also in other gram-negative bacteria, including Xanthomonas campestris. Complementation experiments showed that the xcp gene cluster of P. aeruginosa restored protein secretion in an X. campestris secretion mutant. The secretion gene cluster of X. campestris however, restored secretion capacity in P. aeruginosa mutants only to a low degree. Two heterologous proteins were not secreted by P. fluorescens and P. aeruginosa. The results suggest the presence of a similar two-step protein secretion mechanism in different gram-negative bacteria, which however, is not always functional for heterologous proteins. PMID- 1921978 TI - Construction of a fusion gene comprising the Taka-amylase A promoter and the Escherichia coli beta-glucuronidase gene and analysis of its expression in Aspergillus oryzae. AB - Northern blot analysis of glucose-grown and starch-grown mycelia of Aspergillus oryzae RIB40 was conducted using the cloned Taka-amylase A (TAA) gene as a probe. The amount of mRNA homologous to the TAA gene was increased when this fungus was grown with starch as a sole carbon source. In order to analyze the induction mechanism, we inserted the Escherichia coli uidA gene encoding beta-glucuronidase (GUS) down-stream of the TAA promoter and introduced the resultant fusion gene into the A. oryzae genome. Production of a functional GUS protein was induced by starch, but not by glucose. When the effects of various sugars on expression of the fusion gene were examined, the results suggested that the expression of the fusion gene was under control of the TAA gene promoter. PMID- 1921979 TI - DNA sequences in chromosomes II and VII code for pyruvate carboxylase isoenzymes in Saccharomyces cerevisiae: analysis of pyruvate carboxylase-deficient strains. AB - A gene encoding pyruvate carboxylase has previously been isolated from Saccharomyces cerevisiae. We have isolated a second gene, PYC2, from the same organism also encoding a pyruvate carboxylase. The gene PYC2 is situated on the right arm of chromosome II between the DUR 1, 2 markers and the telomere. We localized the previously isolated gene, which we designate PYC1, to chromosome VII. Disruption of either of the genes did not produce marked changes in the phenotype. However, simultaneous disruption of both genes resulted in inability to grow on glucose as sole carbon source, unless aspartate was added to the medium. This indicates that in wild-type yeast there is no bypass for the reaction catalysed by pyruvate carboxylase. The coding regions of both genes exhibit a homology of 90% at the amino acid level and 85% at the nucleotide level. No appreciable homology was found in the corresponding flanking regions. No differences in the Km values for ATP or pyruvate were observed between the enzymes obtained from strains carrying inactive, disrupted versions of one or other of the genes. PMID- 1921980 TI - Constitutive heterochromatin in early embryogenesis of Drosophila melanogaster. AB - The formation of constitutive heterochromatin was studied during the embryonic development of Drosophila melanogaster, using the C-banding technique. During embryonic cleavage, C-banded material is not seen in mitotic chromosomes; the differentiation between euchromatin and heterochromatin only occurs at blastoderm. This event correlates with the establishment of position-effect variegation. PMID- 1921981 TI - Molecular analysis of the aidD6::Mu d1 (bla lac) fusion mutation of Escherichia coli K12. AB - In this report we present genetic and biochemical evidence indicating that the aidD6::Mu d1 (bla lac) fusion is an insertion of Mu d1 (bla lac) into the alkB coding sequence. We describe the phenotypic effects resulting from this mutation and compare them with the effects of alkB22, alkA and ada mutations. We also constructed an alkA alkB double mutant and compared its phenotype with that of the single mutant strains. The observation that the methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) resistance of the double mutant is approximately at the level predicted from the additive sensitivity of each of the single mutants suggests that these two gene products act in different pathways of DNA repair. PMID- 1921982 TI - Immunological detection of muscarinic receptor subtype proteins (m1-m5) in rabbit peripheral tissues. AB - Employing subtype-specific antisera, we have measured the relative levels of five muscarinic receptor subtype proteins (m1-m5) in rabbit peripheral tissues. Immunoprecipitation assays demonstrated the presence of four distinct receptor proteins (m1-m4), which showed notable differences in their tissue distribution. Significant amounts of m5 receptors were not detected in any of the tissues examined. High levels of m1 receptors were found in sympathetic ganglia and submaxillary gland. The m1 receptor was the predominant subtype in vas deferens. Muscarinic receptors of the m2 type were present in varying proportions in all tissues examined, being the major subtype in sympathetic ganglia, ileum, and uterus and the only subtype detected in rabbit atrium. The m3 receptor protein was abundant in submaxillary gland but was not detected at appreciable levels in other tissues studied. Receptors of the m4 type represented a major subtype in peripheral lung and were also present, although at lower levels, in uterine and ileal tissues. PMID- 1921983 TI - GTP-binding protein G alpha Z: its down-regulation by dexamethasone and its credentials as a mediator of antigen-induced responses in RBL-2H3 cells. AB - We have investigated the possible role of guanine nucleotide-binding proteins in the process of antigen-induced exocytosis in a cultured rat mast cell line, RBL 2H3 cells. The mRNAs for the alpha subunits of the guanine nucleotide-binding proteins G alpha S (short and long forms), G alpha i-2, G alpha i-3, and G alpha Z were detected by hybridization with G alpha-specific oligonucleotide probes. The corresponding proteins were identified in membranes of RBL-2H3 cells on the basis of size, immunoreactivity with specific antibodies, and their ability to serve as substrates for ADP-ribosylation by cholera toxin or pertussis toxin. Treatment of cells with as little as 10(-9) to 10(-7) M dexamethasone markedly decreased the amount of G alpha Z mRNA and membrane G alpha Z, as well as the responsiveness of the cells to antigen stimulation. In the same cells, the exposure to dexamethasone caused an increase in the amounts of certain other G alpha subunits, particularly G alpha i-3, and in the responsiveness of the cells to an adenosine analog, N(ethylcarboxamido)-adenosine. Because of the apparent decrease in G alpha Z mRNA and protein in dexamethasone-treated cells and the fact that neither cholera toxin nor pertussis toxin inhibits the stimulatory signals to antigen [J. Biol. Chem. 265:745-753 (1990)], we suggest that G alpha Z is a potential candidate for regulating the early signals in antigen-stimulated RBL-2H3 cells. PMID- 1921984 TI - Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity. AB - Carbonyl reductase (NADPH: secondary-alcohol oxidoreductase; EC 1.1.1.184), a widely distributed NADPH-dependent enzyme considered as both an aldo-keto reductase and a quinone reductase, was cloned from a human liver genomic library and transiently expressed in COS7 cells. The gene contains 3142 bases comprising three exons and two introns. The absence of a CAAT and TATA box and the presence of a GC-rich island are characteristic of many "housekeeping" genes. Transient expression of the genomic gene in COS7 cells using an expression vector containing an SV40 origin of replication resulted in a greater than 50-fold increase in both menadione reductase activity and daunorubicin reductase activity, suggesting that both activities are derived from the same enzyme. Carbonyl reductase mRNA levels reflected enzyme activity levels in the transfected cells. Other parameters, such as pH profile, cofactor requirements, substrates, and inhibitors, were similar to those of carbonyl reductase purified by other investigators. Potential regulatory elements with consensus sequences for two GC boxes and the transcriptional activator protein AP-2 were present upstream of the transcriptional start site. Although the precise role of carbonyl reductase is unknown, the enzyme is involved in drug metabolism and in the reduction of activated carbonyl compounds. Its ability to act as a quinone reductase also implies a potential to modulate oxygen free radicals. PMID- 1921985 TI - 2'-Deoxy-6-thioguanosine 5'-triphosphate as a substrate for purified human DNA polymerases and calf thymus terminal deoxynucleotidyltransferase in vitro. AB - 2'-Deoxy-6-thioguanosine 5'-triphosphate (S6dGTP), a metabolite of the antileukemia agent 6-thioguanine, was evaluated as a substrate for purified human DNA polymerases. Using bacteriophage M13 single-strand DNA as a template, S6dGTP substituted efficiently for dGTP and stimulated DNA synthesis in reactions without dGTP, with DNA polymerases alpha, delta, and gamma from the human leukemia cell line K562. The apparent Km values for dGTP and S6dGTP were very similar, i.e., 1.2 microM each for polymerase alpha, 2.8 and 3.6 microM, respectively, for polymerase delta, and 0.8 microM each for polymerase gamma; however, the relative Vmax values for the modified nucleotide were 25-50% lower than those of the corresponding natural substrate. Using a highly sensitive electrophoretic assay of chain elongation across M13mp9 (+)-strand DNA by the aforementioned human DNA polymerases, S6dGTP was shown to be incorporated at the 3' end of the nascent growing DNA chain, and the patterns of chain extension with S6dGTP as substrate were identical to those obtained in the presence of dGTP. There were no major differences using S6dGTP in place of dGTP with these DNA polymerases; however, at higher concentrations (1-10 microM) the analog stimulated primer elongation in reactions without dATP, indicating some misincorporation at sites of S6G.T base pairs during DNA synthesis. Using p(dA)12 18 as the initiator for calf thymus terminal deoxynucleotidyltransferase, S6dGTP inhibited the incorporation of all four natural deoxyribonucleoside 5' triphosphates into the primer, in a competitive manner. The apparent Ki values for the analog were 6-20 times lower than the Km values for the four endogenous substrates. As a substrate, S6dGTP was added to the 3'-hydroxyl termini of primer, although tailing efficiency with the analog was lower than that in the presence of the natural substrate. These findings indicate that S6dGTP is a relatively good substrate for several mammalian DNA polymerases, including terminal deoxynucleotidyltransferase. PMID- 1921987 TI - Identification of amino acid residues involved in dendrotoxin block of rat voltage-dependent potassium channels. AB - alpha-Dendrotoxin (DTX) is a 60-amino acid peptide belonging to the family of mamba snake neurotoxins; it is a potent blocker of some but not all voltage-gated potassium currents. Potassium currents recorded from oocytes injected with cloned potassium channel RNAs also vary in sensitivity to DTX. Expression of channels that were chimeras of the DTX-sensitive channel RBK2 and the DTX-insensitive channel RGK5 showed that the putative extracellular loop between transmembrane domains S5 and S6 contributes strongly to DTX sensitivity. Mutation of two residues (Ala352Glu353) in this region of RBK1 to conform to those at equivalent positions in RGK5 (Pro374Ser375) reduced the potency of DTX about 70-fold, and the substitution of Tyr379 in RBK1 by its counterpart in RGK5 (His401) caused an additional 2.5-fold decrease in sensitivity. Converse substitutions in RGK5 significantly increased sensitivity to DTX. The results suggest that these residues contribute significantly to the channel-toxin interaction, providing further evidence that the S5-S6 loop lies at or near the external mouth of the channel, where DTX binding leads to channel occlusion. They offer a molecular explanation for the differences in DTX sensitivity observed among native potassium channels. PMID- 1921986 TI - Sensitization of adenylyl cyclase by P2 purinergic and M5 muscarinic receptor agonists in L cells. AB - Many hormones have been shown to activate phospholipase C, which results in the hydrolysis of membrane polyphosphoinositides, such as phosphatidylinositol 4,5 bisphosphate (PIP2). Two second messengers are known to be produced by PIP2 hydrolysis, 1,2-diacylglycerol, an endogenous activator of a family of enzymes called protein kinase C (PKCs), and inositol 1,4,5-trisphosphate, which raises free levels of intracellular Ca2+. Treatment of various cells with 4 beta-phorbol 12-myristate 13-acetate (PMA), a specific exogenous activator of PKCs, causes an enhancement or sensitization of adenylyl cyclase activities. This finding prompted us to examine the effects of direct hormonal activation of PIP2 hydrolysis on the sensitization of adenylyl cyclase. Liao et al. [J. Biol. Chem. 265:11273-11284 (1990)] have shown that P2 purinergic receptor agonists such as ATP and muscarinic receptor agonists such as carbachol stimulate PIP2 hydrolysis in L cells expressing the M5 muscarinic acetylcholine receptor. We investigated the effects of these hormones on adenylyl cyclase and contrasted these effects with the sensitizing effects of PMA. We found that ATP pretreatment of two different types of L cells resulted in a rapid 50-150% sensitization of prostaglandin E1-, epinephrine-, and forskolin-stimulated adenylyl cyclase activity, with an EC50 of 3 microM ATP. This effect was qualitatively similar to that caused by 10 nM PMA. The enhancement of adenylyl cyclase activity was associated with an increase in the Vmax for hormonal stimulation and with a lack of significant effects of ATP on the EC50. The effect was completely eliminated when adenylyl cyclase was assayed in the presence of high free Mg2+ levels (10 mM). Down-regulation of PKCs with long term PMA treatment did not affect the ATP induced sensitization of adenylyl cyclase, although the PMA-induced sensitization of adenylyl cyclase was eliminated. In contrast to the effects of ATP and PMA, treatment of the cells with carbachol alone had no effect on adenylyl cyclase; however, in combination with nanomolar concentrations of PMA, synergism of the sensitization of adenylyl cyclase was observed. These data indicate that the activation of P2 purinergic receptors by ATP, and possibly activation of M5 muscarinic receptors by carbachol, may be important in the signal transduction pathways leading to the increases in the responsiveness of hormone-stimulated adenylyl cyclase. PMID- 1921988 TI - Reversed siderophores as antimalarial agents. II. Selective scavenging of Fe(III) from parasitized erythrocytes by a fluorescent derivative of desferal. AB - We introduce here a fluorescent derivative of desferrioxamine B (DFO) that retains the high affinity of the parent compound and displays a powerful inhibition of intraerythrocytic Plasmodium falciparum growth. NBD-DFO was synthesized by coupling 7-Nitrobenz-2-oxa-1,3-diazole (NBD) to the terminal amino group of DFO. The NBD group at this position renders the DFO molecule more lipophilic and imparts to it fluorescent properties. The novel NBD-DFO probe displays a unique combination of chemical and biological properties, such as 1) improved and selective permeation properties across membranes of P. falciparum infected erythrocytes, 2) improved efficacy as an inhibitor of intraerythrocytic P. falciparum growth (including multidrug-resistant strains), 3) demonstrable Fe3+ scavenging within parasitized red cells, and 4) usefulness as a sensitive and versatile analytical tool for quantitative assessment of Fe3+ and for following iron-scavenging processes, because the fluorescence of NBD-DFO is demonstrably quenched upon complexation with Fe3+. PMID- 1921989 TI - Post-translational modification of proteins by 15-carbon and 20-carbon isoprenoids in three mammalian cell lines. AB - A number of cellular proteins, including p21ras, lamin B, and the G-protein gamma subunits, undergo post-translational modification by 15-carbon farnesyl or 20 carbon geranylgeranyl isoprenoid moieties derived from pyrophosphate intermediates of the cholesterol biosynthetic pathway. In this study, isoprenylated proteins in three mammalian cell lines (Hela cells, Rat-6 fibroblasts and COS cells) were radiolabeled with an isoprenoid precursor, [3H]mevalonate, and resolved by SDS gel electrophoresis. Groups of proteins with different molecular masses were eluted from the gels and the chain-lengths of the radiolabeled isoprenyl groups, released from the proteins by Raney-nickel catalyzed desulfurization, were established by gel permeation chromatography. 15 Carbon and 20-carbon isoprenyl groups were found in separate classes of proteins within each cell line. With the exception of p21ras, which incorporated a 15 carbon group when expressed in COS cells, the proteins in the region of the 21-28 kDa ras-related GTP binding proteins contained mostly 20-carbon isoprenyl chains. In contrast, proteins belonging to the 66-72 kDa nuclear lamin family, as well as unidentified proteins with molecular masses of 41-46 kDa and 53-55 kDa, contained predominantly 15-carbon isoprenyl chains. The chain-lengths of the isoprenoids associated with particular classes of proteins did not vary from one cell line to another, suggesting that the nature of the isoprenoid modification (farnesyl versus geranylgeranyl) is determined by intrinsic structural features of the proteins, rather than the cell type in which the proteins are expressed. PMID- 1921990 TI - Initiation and regulation mechanisms of ribosomal RNA transcription in the eukaryote Acanthamoeba castellanii. AB - Acanthamoeba rRNA transcription involves the binding of a transcription initiation factor (TIF) to the core promoter of rDNA to form the preinitiation complex. This complex is formed in the absence of RNA polymerase I, and persists for multiple rounds of initiation. Polymerase I next binds to form the initiation complex. This binding is DNA sequence-independent, and is directed by protein protein contacts with TIF. DNA melting occurs in a separate step. In contrast to most prokaryotic transcription, melting occurs only following nucleotide addition and beta-gamma hydrolysis of ATP is not required as for polymerase II. Growth dependent regulation of rRNA transcription is accomplished by modification of RNA polymerase I. The inactive form of polymerase (PolE) is unable to bind to the promoter and has altered heat stability. PolE is still active in elongation; thus, the modification affects the polymerase site involved in TIF contact. Modification of a polymerases I and III common subunit has been detected leading to the suggestion that transcription of stable RNAs of the ribosome might be co regulated by this mechanism. PMID- 1921991 TI - Complementary in vivo and in vitro analyses of the interactions between the cis acting elements of the rat rDNA promoter. AB - Two transcription factors, rat UBF (rUBF) and rat SL-1 are required for the efficient transcription of the rat promoter in vitro. In vitro studies have established that two broadly defined cis-acting domains, the core promoter element and the upstream promoter element, cooperate to direct correct transcription by RNA polymerase I. The ability of UBF to bind to two linker scanning mutants of the upstream promoter element, which did not respond to the addition of UBF in in vitro transcription assays, was assessed by DNase footprinting. UBF protected the same region of the promoter in the linker scanning mutant in BSM 129/124 as it did in the wild-type, but did not yield a typical footprint over the promoter in the linker-scanning mutant BSM 106/101. Previously we reported that promoters with mutant core promoters elements, either the guanine at -16 or -7 substituted by an adenine, were inactive in vitro unless the assays were supplemented with UBF. Those results suggested that the binding of UBF upstream of the core was required for the promotion of transcription. The interactions between the core and upstream promoter elements were assessed by constructing double mutants of the promoter. In two constructs the conserved guanines at either -16 or -7 were altered in a deletion mutant (-86) that did not respond to UBF. In a third construct the guanine at -16 in BSM 129/124 was changed to an adenine. These bidomain mutant constructs did not respond to the addition of UBF in an in vitro transcription assay, confirming that the rescue of the core promoter mutants requires an intact and functional upstream promoter element.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1921992 TI - Trans-acting factors involved in species-specificity and control of mouse ribosomal gene transcription. AB - Faithful and efficient transcription initiation at the mouse ribosomal gene promoter requires besides RNA polymerase I (pol I) four polypeptide trans-acting factors, termed TIF-IA, TIF-IB, TIF-IC, and mUBF. We have partially purified these proteins from cultured Ehrlich ascites cells and show that in the presence of TIF-IA and TIF-IB, pol I directs very low amounts of specific transcripts. Neither TIF-IC nor mUBF on their own significantly stimulate the efficiency of template utilization. However, both factors together strongly activate transcription. Interestingly, factor TIF-IB - the murine homologue of human SL1 - fails to program a human extract to transcribe the murine template, but requires its homologous RNA polymerase I. This finding implicates that not only some rDNA transcription factors but also pol I exhibits species-specific differences. The growth-related factor TIF-IA, on the other hand, stimulates both mouse and human rDNA transcription. This regulatory factor whose amount or activity fluctuates according to the proliferation rate of the cells, is functionally inactivated by antibodies against cdc2 protein kinase. This result together with the observation that transcription is stimulated by ATP-gamma S, an ATP analogue which is a substrate for protein kinases but not for protein phosphatases, strongly suggests that post-translational protein modification is involved in rDNA transcription regulation. PMID- 1921993 TI - Expression of mouse and frog rRNA genes: transcription and processing. AB - This article summarizes a number of lines of investigation of rRNA gene expression that are ongoing in the laboratory. These studies focus on mouse and frog, two distant vertebrate species. One major conclusion is that the basic properties of rRNA gene expression appear remarkably well conserved in evolution, with only relatively minor perturbations between frog and mouse, contrary to the common interpretation of the species-selectively between mouse and human rDNA transcription (e.g., 1). This is true both for the process of rDNA transcription and for the subsequent rRNA processing event. PMID- 1921994 TI - Transgenic animals as a tool for studying the effect of the c-myc proto-oncogene on cardiac development. AB - Transgenic animals provide a model system to elucidate the role of specific proteins in development. This model is now being used increasingly in the cardiovascular system to study cardiac growth and differentiation. During cardiac myocyte development a transition occurs from hyperplastic to hypertrophic growth. In the heart the switch from myocyte proliferation to terminal differentiation is synchronous with a decrease in c-myc mRNA abundance. To determine whether c-myc functions to regulate myocyte proliferation and/or differentiation, we examined the in vivo effect of increasing c-myc expression during fetal development and of preventing the decrease in c-myc mRNA expression that normally occurs during myocyte development. The model system used was a strain of transgenic mice exhibiting constitutive expression of c-myc mRNA in cardiac myocytes throughout development. Increased c-myc mRNA expression is associated with both atrial and ventricular enlargement in the transgenic mice. This increase in cardiac mass is secondary to myocyte hyperplasia, with the transgenic hearts containing greater than twice as many myocytes as nontransgenic hearts. The results of this study indicate that constitutive expression of c-myc mRNA in the heart during development results in enhanced hyperplastic growth, and suggest a regulatory role for the c-myc protooncogene in cardiac myogenesis. PMID- 1921995 TI - Multiple functional enhancer motifs of rat ribosomal gene. AB - Previous studies from this laboratory have characterized a 174 bp enhancer element which is located 2 kb upstream of the initiation site. Half of the enhancer action is controlled by a 37 bp element at the 3' end of the 174 bp region. We now report that a 43 bp adjacent domain which is located upstream of the 37 bp element constitutes an additional motif of the rDNA enhancer. When the plasmid consisting of the 43 bp DNA upstream of the rDNA core promoter was transcribed in a fractionated rat tumor cell extract (fraction DE-B), transcription of rDNA was augmented 4 fold. Electrphoretic mobility shift and DNAase I footprinting analyses showed that the purified 37 bp enhancer (E1) binding protein, (E1BF) not only interacted with the enhancer motif E1 but also interacted with the neighbouring 43 bp enhancer domain E2. The specificity of the binding was demonstrated by competition with unlabelled 37 bp and 43 bp fragment and lack of competition with nonspecific DNAs in the mobility shift assay. These studies have shown that a single pol I transcription factor can bind to multiple enhancer domains with no significant sequence homologies and such multiple interactions may result in maximal transcription of ribosomal gene from the core promoter. PMID- 1921996 TI - Termination of transcription of ribosomal RNA in Saccharomyces cerevisiae. AB - We have attempted to determine the site of termination of transcription of ribosomal RNA in the yeast, Saccharomyces cerevisiae. While a quantitative description of the termination sites of RNA polymerase I is not possible using presently available methods, we conclude that transcription of most molecules continues through a large portion of the adjacent enhancer region. There are two potential termination sites within the enhancer, one of which is near the binding site of the DNA binding protein REBI. In addition there is an apparently fail safe termination site approximately 950 nucleotides beyond the 3' end of 35S ribosomal precursor RNA. Processing at the end of 35S RNA influences the choice of downstream termination site. Conversely downstream sequences also influence the site of termination. PMID- 1921997 TI - Stimulation of ribosomal RNA synthesis during hypertrophic growth of cultured heart cells by phorbol ester. AB - Primary cultures of neonatal cardiac myocytes were used to determine the effects of tumor-promoting phorbol esters on ribosomal RNA (rRNA) synthesis during myocyte growth. Treatment of myocytes with phorbol-12, 13-dibutyrate (PDBu) increased protein accumulation by 25% and RNA content by 20%. Rates of rRNA synthesis were measured to assess the mechanism by which rRNA accumulated during myocyte growth. Rates of rRNA synthesis were determined from the incorporation of [3H]uridine into UMP of purified rRNA and the specific radioactivity of the cellular UTP pool. After 24h of PDBu treatment, cellular rates of 18S and 28S rRNA synthesis were accelerated by 67% and 64%, respectively. The increased rate of rRNA synthesis accounted for the net increase in myocyte rRNA content after PDBu treatment. PMID- 1921998 TI - Coordinate expression of ribosomal protein genes in yeast as a function of cellular growth rate. AB - The rate of ribosome formation in yeast is precisely adjusted to the physiological demands of the cell. During all growth conditions a balance is maintained in the production of all ribosomal constituents. Coordinate expression of the ribosomal protein (rp) genes is primarily accomplished at the transcriptional level. Transcription activation of the majority of the rp-genes is mediated through common upstream activating sequences, so-called RPG boxes, which occur usually in a tandem at a distance of 200-500 bp from the start codon. These RPG-boxes represent binding sites for a transcriptional activator, called TUF or RAP. The concentration of TUF parallels the cellular growth rate and evidence exists that the response of rp-genes upon nutritional changes is mediated by this factor. Recent findings indicate that TUF/RAP also activates other gene families involved in cellular growth rate. Furthermore, this multifunctional protein also binds to the mating-type silencer and telomeres in yeast. Some other rp-genes (e.g. those encoding S33 and L45) do not contain an RPG-box. They appear to be activated by another multifunctional protein, called ABF1 or SUF, by binding to another nucleotide motif. This multifunctional protein also activates other gene families, and in addition binds to the mating type silencer and ARS-elements. PMID- 1921999 TI - Regulation of ribosome biogenesis in differentiated rat myotubes. AB - The rate of ribosome biogenesis is closely coupled with cell proliferation, representing a unique model system for studying gene regulation. Terminal differentiation of rat L6 myoblasts, an example of a rapidly proliferating population of cells being converted into a non-dividing syncytial population, results in an 80% decline in the rate of ribosome accumulation. Ribosome production during myogenesis is regulated by a down-shift in the rate of rRNA accumulation, controlled at the level of transcription by specific trans-acting factors. The synthesis of both ribosomal proteins and 5S rRNA remains unchanged in myotubes, however, resulting in an over-production of these precursors. The excess molecules are rapidly degraded, preventing the accumulation of a static pool of ribosome components. PMID- 1922000 TI - Glucocorticoid regulation of rRNA synthesis. AB - Glucocorticoids inhibit transcription of the genes encoding rRNA (rDNA) in P1798 lymphoma cells. This is due to a decrease in the amount or activity of a transcription factor, called TFIC. TFIC has been purified to apparent homogeneity and the properties of this protein have been investigated in detail. TFIC is tightly associated with RNA polymerase I. The data indicate that TFIC is a bona fide initiation factor that is required for formation of the first phosphodiester bond of nascent pre-rRNA. Extracts from dexamethasone-treated cells are devoid of this factor and cannot form initiated complexes in vitro. PMID- 1922001 TI - Serum, insulin and phorbol esters stimulate rRNA and tRNA gene expression in both dividing and nondividing Drosophila cells. AB - The expression of genes that code for the large ribosomal RNAs (rRNAs) and tRNAs can be regulated by calcium, serum, insulin and a tumor-promoting phorbol ester, TPA. These effectors can rapidly alter rRNA and tRNA synthesis in dividing and nondividing Drosophila cells. In an in vitro assay system of the nondividing cells of the male accessory glands, calcium, insulin and TPA were shown to increase both rRNA and tRNA synthesis. Exposure of actively dividing Drosophila culture cells to differing serum concentrations or TPA also altered rRNA and tRNA synthesis. Nuclear run-on assays demonstrate that the exposure of these cells to increased serum concentrations coordinately alters RNA polymerase I loading on both 18S and 28S rDNA. These data indicate that calcium, growth factors and a tumor-promoter each can signal changes in ribosomal and tRNA gene expression. PMID- 1922002 TI - Biological functions of proteoglycans: use of specific inhibitors of proteoglycan synthesis. AB - The use of specific inhibitors of proteoglycan synthesis have demonstrated essential functions for these molecules. Proteoglycans do not appear to be essential for cell viability or proliferation but are necessary for stable assembly of ECM and functional cell-ECM interaction. Because of their ability to nearly completely abolish ECM assembly in cell culture systems, proteoglycan synthesis inhibitors are useful tools to examine effects of ECM on the phenotypic behavior of cells. Despite its usefulness, the use of proteoglycan synthesis inhibitors has some drawbacks. The most significant of these is the fact that synthesis of all proteoglycans is inhibited, making it difficult to assign a particular function to a specific proteoglycan type. For this reason, inhibition studies need to be done in conjunction with additional biochemical, immunological or molecular biological studies. PMID- 1922003 TI - The effect of culture and membrane potential on Go alpha expression in neonatal rat cardiac myocytes. AB - The effects of culture and membrane potential on Go alpha 39 expression were examined in neonatal rat cardiac myocytes. During six days of culture, the amount of Go alpha 39 in myocytes increased six-fold. The increase in Go alpha 39 appeared to be programmed, since Go alpha 39 of rat hearts also increased in vivo within three days after birth before declining by six days after birth. Furthermore, the age of the rat from which cardiac myocytes were isolated determined the amount of Go alpha 39 that accumulated in cultured cells with myocytes from two day-old rats producing more Go alpha 39 than myocytes from six day-old rats. In addition, agents which alter membrane potential (KCl and bupivacaine) inhibited the accumulation of Go alpha 39 in cultured myocytes. In an attempt to identify the signaling pathway in which cardiac Go alpha 39 is involved, muscarinic receptor-stimulated inositol phosphate production was examined, but was found to be comparable in myocytes that had six-fold differences in Go alpha 39 content. Thus Go alpha 39 does not appear to couple muscarinic receptors to phospholipase C in rat cardiac myocytes. PMID- 1922004 TI - Molecular control of myogenesis: antagonism between growth and differentiation. AB - Insight into the molecular mechanisms that control establishment of the skeletal muscle phenotype has recently been obtained through cloning of a family of muscle specific regulatory factors that can activate myogenesis when transfected into non-muscle cells. This family of factors, which includes MyoD, myogenin, myf-5, and MRF4, can bind DNA and transactivate muscle-specific genes in collaboration with ubiquitous cellular factors. Growth factors play an antagonistic role in myogenesis by suppressing the actions of the myogenic regulatory factor family. This review will focus on the regulation and mechanism of action of this family of myogenic regulatory factors and on the central role of peptide growth factors in modulating their expression and biological activities. PMID- 1922005 TI - The role of NADPH in the regulation of glucose-6-phosphate and 6-phosphogluconate dehydrogenases in rat adipose tissue. AB - Previous studies examining the regulation of the synthesis of G6PDH and 6PGDH in rat liver and adipose tissue have focused on the induction of these enzymes by different diets and some hormones. In rat liver these enzymatic activities seem to be regulated by a mechanism involving changes in the NADPH requirements. In this paper we have studied the effect of changes in the flux through different NADPH-consuming pathways on G6PDH and 6PGDH levels in adipose tissue and on the NADPH/NADP ratio. The results show that: I) an increase in the consumption of NADPH, caused by the activation of either fatty acid synthesis or detoxification systems which consume NADPH, is paralleled by an increase in the levels of these enzymes; II) when the increase in consumption of NADPH is prevented, the G6PDH and 6PGDH levels do not change. PMID- 1922006 TI - Effect of phenylalanine derivatives on the main regulatory enzymes of hepatic cholesterogenesis. AB - Phenylalanine, phenylpyruvate and phenylacetate produced a considerable inhibition of chick liver mevalonate 5-pyrophosphate decarboxylase while mevalonate kinase and mevalonate 5-phosphate kinase were not significantly affected. Phenolic derivatives of phenylalanine produced a similar inhibition of decarboxylase activity than that found in the presence of phenyl metabolites. The degree of inhibition was progressive with increasing concentrations of inhibitors (1.25-5.00 mM). Simultaneous supplementation of different metabolites in conditions similar to those in experimental phenylketonuria (0.25 mM each) produced a clear inhibition of liver decarboxylase and 3-hydroxy-3-methylglutaryl CoA reductase. To our knowledge, this is the first report on the in vitro inhibition of both liver regulatory enzymes of cholesterogenesis in phenylketonuria-like conditions. Our results show a lower inhibition of decarboxylase than that of reductase but suggest an important regulatory role of decarboxylase in cholesterol synthesis. PMID- 1922007 TI - The effects of pantothenic acid, cysteine and dithiothreitol in intact, reperfused pig hearts. AB - The objective of this study was to augment myocardial tissue levels of amphiphiles using a treatment protocol of pantothenic acid, cysteine and dithiothreitol (DTT) in 24 hr fasted pigs and to test their influence on mechanical recovery in reperfusion. Eighteen pig hearts were extracorporeally perfused aerobically, subjected to regionally reversible ischemia in the left anterior descending perfusion system and reperfused. Nine hearts served as a placebo group; nine hearts were treated. All hearts received trace-labeled palmitate to measure fatty acid oxidation and were perfused with an infusion of 20% Intralipid to augment perfusate levels of fatty acids. Fasting alone in the presence of carbon substrates in the coronary perfusate was not sufficient to de inhibit pantothenic acid kinase such that CoA synthesis was not enhanced. Tissue contents of triacylglycerols and phospholipids in reperfused myocardium were no different than in aerobic heart muscle but free CoA and free and total carnitine were reduced, suggesting a leakage of cytosolic contents across injured sarcolemma. Treatment significantly impaired mechanical recovery during reflow, presumable due to the noxious properties of DTT whose reported effects in heart muscle are wide ranging, difficult to predict in intact hearts and may be harmful. PMID- 1922008 TI - Physico-chemical and immunological characteristics of pituitary prolactin from water buffaloes (Bubalus bubalis). AB - Prolactin (PRL) was purified from freshly frozen pituitary glands of water buffaloes (Bubalus bubalis) by a combination of existing procedures of Ellis and Jiang and Wilhelmi involving serial extraction of different pituitary proteins. The partially purified preparation was further fractionated on DEAE-Sephadex followed by Sephadex G-100 chromatography. This was finally purified on HPLC. This preparation was found to be homogeneous by SDS-PAGE and HPLC and had a single N-terminus amino acid (Threonine). The molecular size was estimated to be 24K +/- 0.5 by SDS-PAGE and approximately 25K by GPC-HPLC. The buffalo PRL gave a dose dependent inhibition curve in a rat liver based radio receptor assay with a potency of 30-35 I.U./mg and also in a partial homologous RIA using 125I-buffalo PRL and rabbit anti-oPRL serum giving a potency of 30 I.U./mg. Metabolic labelling studies using 35SO4(2-) with buffalo pituitary minces showed the incorporation of radioactive sulfate into immunoprecipitable PRL-like material. Physico-chemical characterization of the site of the linkage between sulfate and PRL revealed the presence of Tyr-O-SO4 in bu-PRL. A high affinity monoclonal antibody (MAB) with Ka of 10(10) L/M, belonging to IgG1 isotype, and capable of cross reacting with ovine and bovine PRL was generated. This MAB was conformation specific as reduced and carboxymethylated PRL did not react with it. A homologous RIA system using this MAB has been standardised. PMID- 1922009 TI - Immunoanalysis of calf uterine progesterone receptor: modulation of receptor associated 90 kDa heat-shock protein. f. AB - We have examined the influence of transforming agents on the in vitro modulation of the 90 kDa heat-shock protein (hsp-90) associated with the calf uterine progesterone receptor (PR). This analysis was facilitated by the use of alpha PR6 (Sullivan et al. 1986) (anti-PR monoclonal antibody that recognizes 110 kDa protein of chicken PR, subunit PR-B), which was seen to shift the rate of sedimentation of the untransformed (8S) and thermally transformed (4S) [3H]R5020 receptor complexes from the calf uterine cytosol toward the bottom of the tube. Silver staining of the alpha PR6-purified calf uterine cytosol revealed the presence of two major proteins with Mr 114 kDa and 90 kDa. Affinity-labeling of uterine cytosol with [3H]R5020, however, yielded only one major protein of 114 kDa. Incubation of uterine cytosol with AC88 (Riehl et al. 1985), a monoclonal antibody that recognizes hsp-90, resulted in a precipitation of a single 90 kDa protein which showed electrophoretic mobility similar to the second protein precipitated with alpha PR6. Western blot analysis confirmed that alpha PR6 interacts only with the 114 kDa cytosol protein representing the calf uterine PR. Incubation of PR complexes at 23 degrees C or at 0 degrees C with 0.3 M KCl or 10 mM ATP also caused the dissociation of hsp-90 from the 114 kDa PR protein, although thermal transformation was less effective in dissociating hsp-90 from PR when the ligand binding site was occupied by the antiprogestin RU486. The presence of iodoacetamide (IA) stabilized the nontransformed RU486-bound PR against thermal transformation while there was dissociation of hsp-90 from the R5020-receptor complexes. Results of our study demonstrate that calf uterine PR is represented by a major steroid binding protein of 114 kDa that exists in association with hsp-90. Exposure to transforming conditions leads to dissociation of receptor-associated hsp-90. Furthermore, the inability of IA treated RU486-occupied PR to transform suggests that transformation of agonist bound PR involves SH-groups which must be protected from the inactivating influence of IA. PMID- 1922010 TI - Uteroferrin contains complex and high mannose-type oligosaccharides when synthesized in vitro. AB - Mature uteroferrin (Uf; Mr = 35,500) is a progesterone-induced acid phosphatase secreted by the pig uterus. It contains a single, unphosphorylated, high mannose type oligosaccharide. Endometrial explants cultured in vitro secrete Uf with a Mr of 37,000 (37k Uf) having phosphorylated high mannose oligosaccharides. In this report we demonstrate that 37k Uf contains two N-linked oligosaccharides which are a mixture of complex and high mannose-type oligosaccharides. The complex-type glycopeptides are biantennary and a portion may be fucosylated on the GlcNac of the chitobiose core proximal to the peptide. Only a portion of the high mannose type oligosaccharides are phosphorylated. The remainder appear to be typical Man6 4GlcNac2 oligosaccharides found on mature Uf. PMID- 1922011 TI - Analysis in vitro of uterine estrogen receptor conformation of young and old rats. AB - The conformation of estrogen receptor (ER) and its in vitro transformation by RNase, Urea and ATP were analysed using the uteri of young (16 weeks) and old (92 weeks) rats. Following the digestion of ER with proteolytic enzymes like trypsin and chymotrypsin and the analysis of cleaved fragments by SDS-PAGE, similar pattern is observed in both ages. In vitro transformation of ER by RNase, Urea and ATP shows that the degree of transformation is lower in old than young. Furthermore, the transformed ER from old is less capable of binding to DNA than that from young. Thus our results show that the conformation of ER probably does not change with age, but the degree of transformation and the ability of transformed receptor to bind to DNA decrease with age. PMID- 1922012 TI - Aluminum stimulates the proliferation and differentiation of osteoblasts in vitro by a mechanism that is different from fluoride. AB - Micromolar concentrations of aluminum sulfate consistently stimulated [3H]thymidine incorporation into DNA and increased cellular alkaline phosphatase activity (an osteoblastic differentiation marker) in osteoblast-line cells of chicken and human. The stimulations were highly reproducible, and were biphasic and dose-dependent with the maximal stimulatory dose varied from experiment to experiment. The mitogenic doses of aluminum ion also stimulated collagen synthesis in cultured human osteosarcoma TE-85 cells, suggesting that aluminum ion might stimulate bone formation in vitro. The effects of mitogenic doses of aluminum ion on basal osteocalcin secretion by normal human osteoblasts could not be determined since there was little, if any, basal secretion of osteocalcin by these cells. 1,25 Dihydroxyvitamin D3 significantly stimulated the secretion of osteocalcin and the specific activity of cellular alkaline phosphatase in the human osteoblasts. Although mitogenic concentrations of aluminum ion potentiated the 1,25 dihydroxyvitamin D3-dependent stimulation of osteocalcin secretion, they significantly inhibited the hormone-mediated activation of cellular alkaline phosphatase activity. Mitogenic concentrations of aluminum ion did not stimulate cAMP production in human osteosarcoma TE 85 cells, indicating that the mechanism of aluminum ion does not involve cAMP. The mitogenic activity of aluminum ion is different from that of fluoride because (a) unlike fluoride, its mitogenic activity was unaffected by culture medium changes; (b) unlike fluoride, its mitogenic activity was nonspecific for bone cells; and (c) aluminum ion interacted with fluoride on the stimulation of the proliferation of osteoblastic line cells, and did not share the same rate-limiting step(s) as that of fluoride. PTH interacted with and potentiated the bone cell mitogenic activity of aluminum ion, and thereby is consistent with the possibility that the in vivo osteogenic actions of aluminum ion might depend on PTH. In summary, low concentrations of aluminum ion could act directly on osteoblasts to stimulate their proliferation and differentiation by a mechanism that is different from fluoride. PMID- 1922013 TI - Ontogeny of cytosolic proteins capable of modulating sarcoplasmic reticulum calcium transport in heart muscle. AB - In a previous study we described the inhibitory action of a cytosolic protein fraction from heart muscle on ATP-dependent Ca2+ uptake by sarcoplasmic reticulum (SR); further, this inhibition was shown to be blocked by an inhibitor antagonist, also derived from the cytosol (Narayanan et al. Biochim Biophys Acta 735: 53-66, 1983). The present study investigated the ontogenetic expression of the activities of Ca2+ transport inhibitor and inhibitor antagonist in heart cytosol during fetal and postnatal development of the rat. The SR Ca2+ transport inhibitor activity was undetectable in the cytosol of fetal (15- or 20-days gestation) rat heart but was manifested in the cytosol as early as one day after birth and increased progressively thereafter to reach almost adult levels within the first two weeks of postnatal development. The activity of the SR Ca2+ transport inhibitor antagonist was barely detectable in the near-term (20 days gestation) fetus but increased substantially during early postnatal development, in parallel with the rise in activity of the inhibitor. The ontogenetic appearance and increase in the activities of the Ca2+ transport inhibitor and its antagonist correlated well with the concurrent appearance and increase in the amounts of two polypeptides of apparent molecular weights 43 kDa and 64 kDa, which we have tentatively identified as the inhibitor and inhibitor antagonist, respectively. The co-ordinated expression of both the inhibitor and inhibitor antagonist activities in the cytosol during the early postnatal period parallels the morphogenesis and functional maturation of SR in cardiac muscle suggesting likely involvement of these cytosolic proteins in the physiological regulation of SR function. PMID- 1922014 TI - Arachidonic acid metabolism in cultured adult myocardial cells under short-time hypoxic conditions. AB - The present study utilized a cultured adult myocardial cell model to examine the arachidonic acid metabolism under different cell-damaging and normoxic conditions. Cell injury was caused by short-time hypoxia, calcium ionophore A 23187-triggered cell-damage under hypoxia and cell disruption by freezing and thawing. The current study demonstrates that under the cell-damaging conditions cultured adult heart myocytes resemble myocardial cells under normoxic conditions in metabolizing arachidonic acid into triacylglycerols and phospholipids as the major route (a), in formation of ETYA-inhibitable indomethacin-resistant lipid metabolites in minor amounts (b) and in being independent of calcium overload in the metabolic pathways of arachidonic acid metabolism (c). The ETYA-inhibitable components were resolved by HPLC. There was no evidence in formation of lipoxygenase products. The results were supported by negative hybridisation experiments of the total mRNA isolated from adult myocardial cells with a cDNA probe of a red-cell-specific lipoxygenase mRNA. We conclude from these observations that cell injury does not result in expression of lipoxygenase activities in heart myocytes. PMID- 1922015 TI - Biochemical characteristics of cytosolic and particulate forms of protein tyrosine kinases from N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma. AB - Protein tyrosine kinase (PTK) activities in methyl nitrosourea (MNU)-induced rat mammary carcinoma has been investigated by using poly (glu: tyr; 4:1) as an exogenous substrate. The PTK activity of the mammary carcinoma was almost equally distributed between the particulate and soluble (cytosolic) fractions at 110,000 X g. The activity of the particulate enzyme was stimulated by non-ionic detergent Triton X-100 by about 2-fold whereas the detergent had no effect on the cytosolic form. More than 60% of the particulate enzyme could be solubilized by 5% Triton X 100. Although, both particulate and cytosolic PTKs catalyzed the phosphorylation of several tyrosine containing synthetic substrates to various degrees, poly (glu: tyr; 4:1) was the best substrate (apparent Km. 0.7 mg/ml). Both forms of enzymes utilized ATP as the phosphoryl group donor, with an apparent Km of 40 microM. Among various divalent cations tested, Co2+, Mn2+ and Mg2+ were able to fulfill the divalent cation requirement of both forms of the PTKs. All these cations exerted biphasic effects on the kinase activities, however, Mg2+ was the most potent cation. Agents such as epidermal growth factor, insulin and platelet derived growth factor which stimulate their respective receptor-PTK activities were without effect on PTK activities of mammary carcinoma. On the other hand, though heparin and quercetin inhibited both enzyme activities in a concentration dependent manner, the particulate form was more sensitive to inhibition than the cytosolic form. These data indicate that MNU-induced rat mammary carcinoma expresses both particulate and cytosolic forms of PTKs and that there are significant differences in the properties of the two forms of PTKs. Differential effects of some agents on mammary carcinoma PTKs suggest that these enzymes may be acutely regulated in vivo and could play an important role in mammary carcinogenesis. PMID- 1922016 TI - Effect of erythropoietin on the interaction of concanavalin A with rat erythrocytes. AB - Effect of Erythropoietin (Ep) on the interaction of Concanavalin A (Con A) with rat erythrocytes was studied using 125I-labelled Con A. Binding of Con A to erythrocytes was dependent on time and cell concentration. Starvation caused an elevation of the lectin binding capacity of red cells which again came down towards the normal level on Ep administration to starved rats. Binding of Con A to erythrocytes decreased linearly with increasing concentration of Ep. Specificity of binding was confirmed by inhibition studies with alpha-methyl-D mannopyranoside (Me Man) Cells from the starved rats compared to those from normal and Ep treated animals were less prone to inhibition by this sugar analog. Positive cooperative binding of Con A to rat erythrocyte was observed at low concentration of Con A but was absent at higher lectin concentrations. Starvation caused an increase in the number of binding sites per cell which returned to normal level after Ep treatment. Under identical conditions, binding affinities were not much changed in these cells. Cells from the starved animals were more susceptible to agglutination compared to those from normal and Ep-treated rats. Microviscosity and cholesterol/phospholipid ratio of red cell membrane decreased in the starved animals which retraced its way back towards the normal level after Ep treatment. PMID- 1922017 TI - Metabolism of glycosaminoglycans in tissues of adjuvant arthritic rat. AB - The metabolic changes in the connective tissue glycosaminoglycans were studied in tissues of adjuvant induced arthritic rats. Arthritic process was induced in rats with the inoculation of Freund's adjuvant containing heat killed Mycobacterium tuberculosis in paraffin oil. The connective tissue glycosaminoglycans were fractionated into sulfated and non-sulfated glycosaminoglycans by chemical and enzymatic methods. The biosynthesis of sulfated glycosaminoglycans was examined using radioactive labeled (35S)-sulfate incorporation measurements into the sulfated glycosaminoglycans in tissues such as liver, kidney, spleen and skin of arthritic rats. The catabolism of glycosaminoglycans was studied by measuring the activity of various connective tissue degrading lysosomal glycohydrolases in tissues of experimental animals. In addition, the changes in the contents of total glycosaminoglycans, mono-sulfated, highly-sulfated and non-sulfated glycosaminoglycans were quantitatively assessed in diseased tissues. Alterations in the metabolism of connective tissue glycosaminoglycans were demonstrated in tissues of arthritic rats. The uptake of (35S)-sulfate into the tissue was found to be increased in liver, kidney and spleen, while that of skin decreased during the process of arthritis. The total glycosaminoglycan content was significantly elevated in diseased tissues compared to normal. Similarly, mono-sulfated, highly sulfated and non-sulfated glycosaminoglycans were found to be increased in arthritic tissues. In addition, the activity of various connective tissue degrading lysosomal glycohydrolases such as beta-glucuronidase, beta-N acetylglucosaminidase, cathepsin B, cathepsin L and collagenolytic cathepsin was increased in tissues of arthritic rat. The results presented in this communication indicate that the characteristic alterations were induced in the metabolism of glycosaminoglycans by the dynamic process of adjuvant arthritis. PMID- 1922018 TI - Creatine kinase activity in normal and hypertrophied rabbit urinary bladder tissue (following partial outlet obstruction). AB - The urinary bladder depends on intracellular ATP to support a number of essential intracellular processes including contraction. The concentration of ATP is maintained by mitochondrial oxidative phosphorylation, cytosolic glycolysis and the cytosolic activity of creatine kinase, the enzyme that catalysis the rapid transfer of a phosphate from creatine phosphate (CP) to ADP resulting in the formation of ATP. Prior studies in this lab and others have demonstrated that mitochondrial respiration is significantly lower in hypertrophied bladder tissue (induced by partial outlet obstruction of the white New Zealand Rabbit). In addition to decreased mitochondrial respiration, there are significant increases in glycolysis and lactic acid formation in the hypertrophied tissue. In view of the increased glycolysis and decreased mitochondrial function in the hypertrophied tissue, and the importance in creatine kinase in maintaining cytosolic levels of ATP, the current study was designed to determine if outlet obstruction induces any changes in the activity of creatine kinase. The following is a summary of the results: 1) The bladder mass increased from 2.2 +/- 0.2 gm to 11.5 +/- 1.6 gm at 7 days following outlet obstruction. 2) The intracellular concentrations of both ATP and CP were significantly reduced in the bladder tissue following 7 days of obstruction. 3) The percent of protein (per tissue mass) was significantly lower in the obstructed bladders, although the percent of soluble protein was similar. 4) Creatine kinase activity of control bladders showed linear kinetics with a Vmax = 1120 nmoles/mg protein/4 min and Km = 147 microM CP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922019 TI - Characterization of new members of the pregnancy-specific beta 1-glycoprotein family. AB - Three cDNAs encoding members of the pregnancy-specific beta 1-glycoprotein (PSG) family were isolated from human term placental cDNA library. All three cDNAs encode proteins with similar domain structure. There is a leader sequence of 34 amino acids followed by an N-domain of 109 amino acids. Immediately after the N domain are one or two copies of a repeating A-domain of 93 amino acids, a B domain of 85 amino acids and a C-domain of variable size. The proteins are highly hydrophilic. However, one of them has an 81-amino acid C-domain which is very hydrophobic and could potentially serve as a membrane attachment site. The putative cell-cell recognition tripeptide, Arg-Gly-Asp, is present in the N domain of two of the proteins. Partial sequence of one of the cDNAs has been found in HeLa cells while cDNAs highly homologous to two of the cDNAs have been found in the fetal liver. Functional roles of the PSG proteins basing on their structure are proposed. PMID- 1922020 TI - Differential binding of rat pituitary-specific nuclear factors to the 5'-flanking region of pituitary and placental members of the human growth hormone gene family. AB - Placental chorionic somatomammotropin (hCS-A or B) and growth hormone variant (hGH-V) are members of the human growth hormone family, and are related by structure and function to pituitary growth hormone (hGH-N). However, while the hGH-N gene is expressed specifically in the anterior pituitary, hGH-V and hCS are produced in the placenta. Hybrid hGH-N, hGH-V and hCS-A genes containing 5' flanking sequences, including the endogenous promoter, are preferentially expressed in rat pituitary tumor (GC) cells, after gene transfer. Since interaction with a pituitary-specific protein (Pit 1) is required for efficient hGH-N as well as rat growth hormone (rGH) gene expression in GC cells, binding of pituitary proteins to the hGH-V and hCS-A promoter sequences was investigated. Rat Pit 1 binds at two locations on the hGH-N gene, a distal (-140/-107) and proximal site (-97/-66), in a similar manner to that observed with the rGH gene. By contrast, efficient Pit 1 binding was seen only to the distal site of the hGH V gene and the proximal site of the hCS-A gene. Although binding of a protein to the distal hCS-A sequences was observed, the site of interaction was truncated ( 140/-116), not pituitary-specific, and was more consistent with the binding of Sp1. These data indicate that rat Pit 1 binds to the placental hGH-V and hCS-A genes and correlates with their promoter activity in GC cells after gene transfer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922021 TI - The conserved carboxy-terminal domain of Saccharomyces cerevisiae TFIID is sufficient to support normal cell growth. AB - We have examined the structure-function relationships of TFIID through in vivo complementation tests. A yeast strain was constructed which lacked the chromosomal copy of SPT15, the gene encoding TFIID, and was therefore dependent on a functional plasmid-borne wild-type copy of this gene for viability. By using the plasmid shuffle technique, the plasmid-borne wild-type TFIID gene was replaced with a family of plasmids containing a series of systematically mutated TFIID genes. These various forms of TFIID were expressed from three different promoter contexts of different strengths, and the ability of each mutant form of TFIID to complement our chromosomal TFIID null allele was assessed. We found that the first 61 amino acid residues of TFIID are totally dispensable for vegetative cell growth, since yeast strains containing this deleted form of TFIID grow at wild-type rates. Amino-terminally deleted TFIID was further shown to be able to function normally in vivo by virtue of its ability both to promote accurate transcription initiation from a large number of different genes and to interact efficiently with the Gal4 protein to activate transcription of GAL1 with essentially wild-type kinetics. Any deletion removing sequences from within the conserved carboxy-terminal region of S. cerevisiae TFIID was lethal. Further, the exact sequence of the conserved carboxy-terminal portion of the molecule is critical for function, since of several heterologous TFIID homologs tested, only the highly related Schizosaccharomyces pombe gene could complement our S. cerevisiae TFIID null mutant. Taken together, these data indicate that all important functional domains of TFIID appear to lie in its carboxy-terminal 179 amino acid residues. The significance of these findings regarding TFIID function are discussed. PMID- 1922022 TI - Dominant inhibitory mutations in the Mg(2+)-binding site of RasH prevent its activation by GTP. AB - We have previously demonstrated that substitution of Asn for Ser at position 17 of RasH yields a dominant inhibitory protein whose expression in cells interferes with endogenous Ras function (L. A. Feig, and G. M. Cooper, Mol. Cell. Biol. 8:3235-3243, 1988). Subsequent structural studies have shown that the hydroxyl group of Ser-17 contributes to the binding of Mg2+ associated with bound nucleotide. In this report, we show that more subtle amino acid substitutions at this site that would be expected to interfere with complexing Mg2+, such as Cys or Ala, also generated dominant inhibitory mutants. In contrast, a Thr substitution that conserves a reactive hydroxyl group maintained normal Ras function. These results argue that the defect responsible for the inhibitory activity is improper coordination of Mg2+. Preferential affinity for GDP, observed in the original Asn-17 mutant, was found exclusively in inhibitory mutants. However, this binding specificity did not completely block the mutant proteins from binding GTP in vivo since introduction of the autophosphorylation site, Thr-59, in 17N Ras resulted in the phosphorylation of the double mutant in cells. Furthermore, inhibitory mutants failed to activate a model downstream target, yeast adenylate cyclase, even when bound to GTP. Thus, the consequence of improper complexing of Mg2+ was to lock the protein in a constitutively inactive state. A model is presented to explain how these properties could cause the mutant protein to inhibit the activation of endogenous Ras by competing for a guanine nucleotide-releasing factor. PMID- 1922023 TI - Chicken vitellogenin gene-binding protein, a leucine zipper transcription factor that binds to an important control element in the chicken vitellogenin II promoter, is related to rat DBP. AB - We screened a chicken liver cDNA expression library with a probe spanning the distal region of the chicken vitellogenin II (VTGII) gene promoter and isolated clones for a transcription factor that we have named VBP (for vitellogenin gene binding protein). VBP binds to one of the most important positive elements in the VTGII promoter and appears to play a pivotal role in the estrogen-dependent regulation of this gene. The protein sequence of VBP was deduced from a nearly full length cDNA copy and was found to contain a basic/zipper (bZIP) motif. As expected for a bZIP factor, VBP binds to its target DNA site as a dimer. Moreover, VBP is a stable dimer free in solution. A data base search revealed that VBP is related to rat DBP. However, despite the fact that the basic/hinge regions of VBP and DBP differ at only three amino acid positions, the DBP binding site in the rat albumin promoter is a relatively poor binding site for VBP. Thus, the optimal binding sites for VBP and DBP may be distinct. Similarities between the VBP and DBP leucine zippers are largely confined to only four of the seven helical spokes. Nevertheless, these leucine zippers are functionally compatible and appear to define a novel subfamily. In contrast to the bZIP regions, other portions of VBP and DBP are markedly different, as are the expression profiles for these two genes. In particular, expression of the VBP gene commences early in liver ontogeny and is not subject to circadian control. PMID- 1922024 TI - Regulation and a possible stage-specific function of Oct-2 during pre-B-cell differentiation. AB - The Oct-2 gene appears to encode a developmental regulator of immunoglobulin gene transcription. We demonstrate that the Oct-2 gene is expressed at low levels in a variety of transformed pre-B-cell lines and is induced specifically in these cells by lipopolysaccharide signalling. This work extends an earlier observation in the pre-B-cell line 70Z/3 and therefore suggests that the inducible expression of the Oct-2 gene, like that of the kappa gene, is a characteristic feature of the pre-B stage of B-cell development. In 70Z/3 cells, the lymphokine interleukin 1 also induces the expression of the Oct-2 and kappa loci. Interestingly, expression of the Oct-2 gene is rapidly induced at the transcriptional level and may not require de novo protein synthesis. Since the changes in the activity of the Oct-2 locus completely correlate with the changes of the activity of the kappa locus, the two genes may be transcriptionally regulated by a common trans acting factor. In 70Z/3 cells, transforming growth factor beta, an inhibitor of kappa-gene induction, blocks the upregulation of Oct-2 but not the activation of NF-kappa B. These results suggest that the combinatorial action of increased levels of Oct-2 and activated NF-kappa B may be necessary for the proper stage specific expression of the kappa locus. PMID- 1922025 TI - Highly conserved residues in the bZIP domain of yeast GCN4 are not essential for DNA binding. AB - Yeast GCN4 and the Jun oncoprotein are transcriptional activators that bind DNA via a bZIP domain consisting of a leucine zipper dimerization element and an adjacent basic region that directly contacts DNA. Two highly conserved alanines (Ala-238 and Ala-239 in GCN4) and an invariant asparagine (Asn-235) in the basic region have been proposed to play important roles in DNA sequence recognition by bZIP proteins. Surprisingly, these conserved residues can be functionally replaced in GCN4 and in a derivative containing the Jun basic region (Jun-GCN4). The ability of an amino acid to functionally substitute for Asn-235 does not correlate with its preference for assuming the N-cap position of an alpha helix. This finding argues against the proposal of the scissors grip model that the invariant asparagine forms an N cap that permits the basic region to bend sharply and wrap around the DNA. In contrast to a prediction of the induced fork model, the pattern of functional substitutions of the conserved alanines together with the results of uracil interference experiments suggests that Ala-238 and Ala-239 do not make base-specific DNA contacts. Finally, the Jun-GCN4 chimeric proteins appear much more active in vivo than expected from their DNA-binding properties in vitro. The mechanistic and evolutionary implications of these results are discussed. PMID- 1922026 TI - Thyroid-specific enhancer-binding protein (T/EBP): cDNA cloning, functional characterization, and structural identity with thyroid transcription factor TTF 1. AB - A cDNA clone encoding a thyroid-specific enhancer-binding protein (T/EBP) was isolated from a rat thyroid-derived FRTL-5 cell lambda gt 11 expression library, using a double-stranded oligonucleotide probe. This oligonucleotide was previously demonstrated to have the strongest binding affinity among three cis acting DNA elements within the thyroid-specific enhancer region located 5.5 kbp upstream of the human thyroid peroxidase gene transcription start site. Nucleotide and deduced amino acid sequences of the cDNA revealed that T/EBP is identical to the previously reported thyroid-specific transcription factor 1 (TTF 1), which binds to the promoter of the rat thyroglobulin gene and controls its thyroid-specific expression. Expression of the T/EBP cDNA under control of the human cytomegalovirus major immediate-early gene promoter conferred thyroid specific enhancer activity of as high as 26-fold to nonpermissive human hepatoma HepG2 cells when cotransfected with a vector containing 6.3 kbp of upstream sequence of the human thyroid peroxidase gene connected to a luciferase reporter gene. T/EBP was further expressed in HepG2 cells by using the vaccinia virus expression system. The expressed protein was partially purified by using sequence specific affinity column chromatography and was further shown, by gel mobility shift experiments, to specifically bind to the enhancer-derived double-stranded oligonucleotide. These results clearly indicate that the binding of T/EBP (TTF-1) to the specific cis-acting enhancer element is largely responsible for thyroid specific enhancer activity. PMID- 1922027 TI - Induction of NF-kappa B DNA-binding activity during the G0-to-G1 transition in mouse fibroblasts. AB - A DNA-binding factor with properties of NF-kappa B and another similar activity are rapidly induced when growth-arrested BALB/c 3T3 cells are stimulated with serum growth factors. Induction of these DNA-binding activities is not inhibited by pretreatment of quiescent cells with the protein synthesis inhibitor cycloheximide. Interestingly, the major NF-kappa B-like activity is not detected in nuclear extracts of proliferating cells, and thus its expression appears to be limited to the G0-to-G1 transition in 3T3 cells. These DNA-binding activities bind many of the expected NF-kappa B target sequences, including elements in the class I major histocompatibility complex and human immunodeficiency virus enhancers, as well as a recently identified NF-kappa B binding site upstream of the c-myc gene. Furthermore, both the class I major histocompatibility complex and c-myc NF-kappa B binding sites confer inducibility on a minimal promoter in 3T3 cells stimulated with serum growth factors. The results demonstrate that NF kappa B-like activities are immediate-early response proteins in 3T3 cells and suggest a role for these factors in the G0-to-G1 transition. PMID- 1922028 TI - Early gene responses to transforming growth factor-beta in cells lacking growth suppressive RB function. AB - The growth-suppressive function of the retinoblastoma susceptibility gene product, RB, has been implicated in the mediation of growth inhibition and negative regulation of certain proliferation related genes by transforming growth factor-beta 1 (TGF-beta 1). Early gene responses to TGF-beta 1 were examined in order to determine their dependence on the cell cycle and on the growth suppressive function of RB. TGF-beta 1, which rapidly elevates the steady-state level of junB and PAI-1 mRNAs and decreases that of c-myc mRNA, induces these responses in S-phase populations of Mv1Lu lung epithelial cells containing RB in a phosphorylated state. Since in this state RB is presumed to lack growth suppressive activity, the response to TGF-beta 1 was also examined in DU145 human prostate carcinoma cells whose mutant RB product lacks growth-suppressive function. In these cells, TGF-beta 1 also decreases c-myc expression at the transcription initiation level. These results suggests that the c-myc, junB, and PAI-1 responses to TGF-beta 1 are not restricted to the G1 phase of the cell cycle and that down-regulation of c-myc expression by TGF-beta 1 can occur through a mechanism independent from the growth-suppressive function of RB. PMID- 1922029 TI - Progesterone enhances target gene transcription by receptor free of heat shock proteins hsp90, hsp56, and hsp70. AB - Steroid receptors regulate transcription of target genes in vivo and in vitro in a steroid hormone-dependent manner. Unoccupied progesterone receptor exists in the low-salt homogenates of target cells as a functionally inactive 8 to 10S complex with several nonreceptor components such as two molecules of 90-kDa heat shock protein (hsp90), a 70-kDa heat shock protein (hsp70), and a 56-kDa heat shock protein (hsp56). Ligand-induced dissociation of receptor-associated proteins such as hsp90 has been proposed as the mechanism of receptor activation. Nevertheless, it has not been established whether, beyond release of heat shock proteins, the steroidal ligand plays a role in modulating receptor activity. To examine whether the release of these nonreceptor proteins from receptor complex results in a constitutively active receptor, we isolated an unliganded receptor form essentially free of hsp90, hsp70, and hsp56. Using a recently developed steroid hormone-responsive cell-free transcription system, we demonstrate for the first time that the dissociation of heat shock proteins is not sufficient to generate a functionally active receptor. This purified receptor still requires hormone for high-affinity binding to a progesterone response element and for efficient transcriptional activation of a target gene. When an antiprogestin, Ru486, is bound to the receptor, it fails to promote efficient transcription. We propose that in the cell, in addition to the release of receptor-associated inhibitory proteins, a distinct hormone-mediated activation event must precede efficient gene activation. PMID- 1922030 TI - Differential DNA binding by monomeric, homodimeric, and potentially heteromeric forms of the thyroid hormone receptor. AB - Binding of the thyroid hormone receptor (TR) to thyroid hormone-responsive elements (TREs) is crucial for regulation of gene expression by thyroid hormone. The TR binds to each half-site of a palindromic TRE separately, as a monomer, or simultaneously, as a homodimer. In addition, the TR monomer interacts with a 42 kDa protein that may be responsible for an increase in the apparent size and stability of the TR-TRE complex after incubation with liver nuclear extract. The multiple DNA-binding forms of the TR contact the TRE differently but compete for binding in a dynamic equilibrium which is highly dependent on the relative concentrations of TR and nuclear protein. Thus, protein-protein interactions are likely to determine the context in which the TR binds to target genes and regulates the transcriptional response to thyroid hormone. PMID- 1922031 TI - Progestins both stimulate and inhibit breast cancer cell cycle progression while increasing expression of transforming growth factor alpha, epidermal growth factor receptor, c-fos, and c-myc genes. AB - This study documents a biphasic change in the rate of cell cycle progression and proliferation of T-47D human breast cancer cells treated with synthetic progestins, consisting of an initial transient acceleration in transit through G1, followed by cell cycle arrest and growth inhibition. Both components of the response were mediated via the progesterone receptor. The data are consistent with a model in which the action of progestins is to accelerate cells already progressing through G1, which are then arrested early in G1 after completing a round of replication, as are cells initially in other phases of the cell cycle. Such acceleration implies that progestins act on genes or gene products which are rate limiting for cell cycle progression. Increased production of epidermal growth factor and transforming growth factor alpha, putative autocrine growth factors in breast cancer cells, does not appear to account for the initial response to progestins, since although the mRNA abundance for these growth factors is rapidly induced by progestins, cells treated with epidermal growth factor or transforming growth factor alpha did not enter S phase until 5 to 6 h later than those stimulated by progestin. The proto-oncogenes c-fos and c-myc were rapidly but transiently induced by progestin treatment, paralleling the well known response of these genes to mitogenic signals in other cell types. The progestin antagonist RU 486 inhibited progestin regulation of both cell cycle progression and c-myc expression, suggesting that this proto-oncogene may participate in growth modulation by progestins. PMID- 1922032 TI - C/EBP-like proteins binding to the functional box-alpha and box-beta of the second enhancer of hepatitis B virus. AB - The second enhancer (enhancer II) of hepatitis B virus is functionally liver specific. Located within an open reading frame of the virus and immediately upstream of the initiation sites of viral major transcripts, enhancer II furnishes a unique model for use in investigating the structure and function of an enhancer. In this study, two functional constituents, a 23-bp box-alpha and a 12-bp box-beta, are identified as being both necessary and sufficient for enhancer II function. Examination of the box-alpha and box-beta sequences reveals a weak homology to the extended consensus for a C/EBP binding site. Gel shift and footprinting analyses indicate that multiple proteins bind to these sequences and thus are candidate transcription factors that mediate the enhancer function. One heat-resistant protein, protein a, and one heat-sensitive protein, protein b, bind to box-alpha. Protein a, which binds to box-alpha in a way indistinguishable from that seen with a recombinant C/EBP, appears not to be identical to C/EBP in that the binding of protein a requires a minimal sequence larger than the canonical C/EBP sites. Two box-beta-binding proteins, c and d, show greater affinity for the C/EBP consensus than for box-beta. However, both proteins c and d are relatively heat sensitive and display a distinct sequence preference from the recombinant C/EBP protein. Since the function of enhancer II is strictly dependent on a bipartite architecture, this system provides a unique model for studies of how the interactions of its binding proteins lead to the enhancer function. PMID- 1922033 TI - Activation of skeletal alpha-actin gene transcription: the cooperative formation of serum response factor-binding complexes over positive cis-acting promoter serum response elements displaces a negative-acting nuclear factor enriched in replicating myoblasts and nonmyogenic cells. AB - Three upstream CBAR cis-acting promoter elements, containing the inner core CC(A/T)6GG of the serum response element (SRE), are required for myogenic cell type-restricted expression of the avian skeletal alpha-actin gene (K.L. Chow and R.J. Schwartz, Mol. Cell. Biol. 10:528-538, 1990). These actin SRE elements display differential binding properties with two distinct nuclear proteins, serum response factor (SRF) and another factor described here as F-ACT1. SRF is able to bind to all actin SREs with various affinities. This multisite interaction is marked by cooperative binding events in that the two high-affinity proximal and distal SREs facilitate the weak central-site interaction with SRF, leading to the formation of a higher-order SRF-promoter complex. Functional analyses reveal that undisrupted multiple SRF-DNA interactions are absolutely essential for promoter activity in myogenic cells. F-ACT1, present at higher levels in nonmyogenic cells and replicating myoblasts than in myotubes, binds solely to the proximal SRE, and its binding is mutually exclusive with that of SRF owing to their overlapping base contacts. The cooperative promoter binding by SRF, however, can effectively displace prebound F-ACT1. In addition, an intact F-ACT1 binding site acts as a negative promoter element by restricting developmentally timed expression in myoblasts. F-ACT1 may therefore act as a repressor of skeletal alpha-actin gene transcription. This interplay between F-ACT1 and SRF may constitute a developmental as well as a physiologically regulated mechanism which modulates sarcomeric actin gene expression. PMID- 1922034 TI - GRR1 of Saccharomyces cerevisiae is required for glucose repression and encodes a protein with leucine-rich repeats. AB - Growth of the yeast Saccharomyces cerevisiae on glucose leads to repression of transcription of many genes required for alternative carbohydrate metabolism. The GRR1 gene appears to be of central importance to the glucose repression mechanism, because mutations in GRR1 result in a pleiotropic loss of glucose repression (R. Bailey and A. Woodword, Mol. Gen. Genet. 193:507-512, 1984). We have isolated the GRR1 gene and determined that null mutants are viable and display a number of growth defects in addition to the loss of glucose repression. Surprisingly, grr1 mutations convert SUC2, normally a glucose-repressed gene, into a glucose-induced gene. GRR1 encodes a protein of 1,151 amino acids that is expressed constitutively at low levels in yeast cells. GRR1 protein contains 12 tandem repeats of a sequence similar to leucine-rich motifs found in other proteins that may mediate protein-protein interactions. Indeed, cell fractionation studies are consistent with this view, suggesting that GRR1 protein is tightly associated with a particulate protein fraction in yeast extracts. The combined genetic and molecular data are consistent with the idea that GRR1 protein is a primary response element in the glucose repression pathway and is required for the generation or interpretation of the signal that induces glucose repression. PMID- 1922035 TI - Identification and characterization of a novel cytoskeleton-associated pp60src substrate. AB - Transformation of cells by the src oncogene results in elevated tyrosine phosphorylation of two related proteins, p80 and p85 (p80/85). Immunostaining with specific monoclonal antibodies revealed a striking change of subcellular localization of p80/85 in src-transformed cells. p80/85 colocalizes with F-actin in peripheral extensions of normal cells and rosettes (podosomes) of src transformed cells. Sequence analysis of cDNA clones encoding p80/85 revealed an amino-terminal domain composed of six copies of a direct tandem repeat, each repeat containing 37 amino acids, a carboxyl-terminal SH3 domain, and an interdomain region composed of a highly charged acidic region and a region rich in proline, serine, and threonine. The multidomain structure of p80/85 and its colocalization with F-actin in normal and src-transformed cells suggest that these proteins may associate with components of the cytoskeleton and contribute to organization of cell structure. PMID- 1922036 TI - Recombinant 43-kDa USF binds to DNA and activates transcription in a manner indistinguishable from that of natural 43/44-kDa USF. AB - USF is a cellular factor involved in the transcriptional regulation of several cellular and viral promoters. Purified USF from HeLa cells (HeLa USF) consists of 43- and 44-kDa polypeptides which show independent binding to a specific DNA element. A cDNA encoding the 43-kDa species has been previously cloned. We show here that the purified form of bacterially expressed 43-kDa USF (i) exists in solution as a dimer whose formation is greatly favored under reducing conditions, (ii) binds to its cognate DNA sequence in a manner indistinguishable from that of HeLa USF, and (iii) is as efficient as HeLa USF in stimulating transcription from target promoters in a reconstituted cell-free system. Additional data indicate that the 44-kDa component of HeLa USF is immunologically unrelated to the 43-kDa polypeptide but is associated with it in HeLa cell extracts. These results suggest that the 43-kDa component possesses an intrinsic DNA binding and transcriptional activation potential and that the 44-kDa USF component of the natural USF complex may have some regulatory role. PMID- 1922037 TI - Retrovirus-induced insertional mutagenesis: mechanism of collagen mutation in Mov13 mice. AB - The Mov13 mouse strain carries a mutation in the alpha 1(I) procollagen gene which is due to the insertion of a Moloney murine leukemia provirus into the first intron. This insertion results in the de novo methylation of the provirus and flanking DNA, the alteration of chromatin structure, and the transcriptional inactivity of the collagen promoter. To address the mechanism of mutagenesis, we reintroduced a cloned and therefore demethylated version of the Mov13 mutant allele into mouse fibroblasts. The transfected gene was not transcribed, indicating that the transcriptional defect was not due to the hypermethylation. Rather, this result strongly suggests that the mutation is due to the displacement or disruption of cis-acting regulatory DNA sequences within the first intron. We also constructed a Mov13 variant allele containing a single long terminal repeat instead of the whole provirus. This construct also failed to express mRNA, indicating that the Mov13 mutation does not revert by provirus excision as has been observed for other retrovirus-induced mutations. PMID- 1922038 TI - Two components of Saccharomyces cerevisiae transcription factor IIIB (TFIIIB) are stereospecifically located upstream of a tRNA gene and interact with the second largest subunit of TFIIIC. AB - A novel photocrosslinking method has been used to identify the components of transcription factor IIIB (TFIIIB) and TFIIIC that associate with DNA upstream of the Saccharomyces cerevisiae SUP4 tRNATyr gene and to map these components to specific positions in DNA. When TFIIIC binds to the tRNA gene, only its second largest subunit (135 kDa) is accessible for reaction with a photoactive nucleotide, 5-[N-(p-azidobenzoyl)-3-aminoallyl]-dUMP, inserted into DNA upstream of the transcriptional start. Formation of TFIII(C + B)-tRNA gene complexes specifically brings two additional polypeptides (90 and 70 kDa) within reach of upstream photoprobes. A collection of 13 probes has been used to map the locations of these three proteins along a 45-bp segment of DNA upstream of the transcriptional start site. Evidence is presented that the 90- and 70-kDa polypeptides are separate and distinct components of yeast TFIIIB, that they are accessible to crosslinking on opposite sides of the DNA helix in a 6-bp segment centered 35 bp upstream of the tRNATyr gene transcriptional start, and that they interact with the second-largest subunit of TFIIIC. PMID- 1922039 TI - Novel protein-DNA interactions associated with increased immunoglobulin transcription in response to antigen plus interleukin-5. AB - Although much has been learned about basal levels of immunoglobulin (Ig) transcription, the regulatory effects of cytokines and antigen (Ag) upon Ig expression in lymphocytes have not been fully characterized. We previously reported that Ag plus interleukin-5 (IL-5) caused increased steady-state Ig mRNA levels in Ag-specific cell lines. In this study, we have identified a region between -250 and -125 bp 5' of the Ig transcription start site that is necessary for the induction of increased mu mRNA levels by Ag plus IL-5. Mobility shift and UV cross-linking studies indicated that IL-5 plus Ag induced increased protein binding to this region. Furthermore, this sequence was found to be closely related to another A + T-rich sequence at -525 bp 5' of the transcription start site. Both sequences exhibited similar B-cell-specific and inducible protein binding. Our data suggest that treatment with IL-5 plus Ag induces several DNA binding proteins, some of which may participate in increasing Ig transcription above basal levels by binding to sequences 5' of the octamer motif. PMID- 1922040 TI - Identification of a matrix-associated region 5' of an immunoglobulin heavy chain variable region gene. AB - In the accompanying report (C. F. Webb, C. Das, S. Eaton, K. Calame, and P. Tucker, Mol. Cell. Biol. 11:5197-5205, 1991), we characterize B-cell-specific protein-DNA interactions at -500 and -200 bp upstream of the mu immunoglobulin heavy chain promoter whose abundances were increased by interleukin-5 plus antigen. Because of the high A + T/G + C ratio of these sequences and the consistent findings by others that enhancer- and promoterlike regions are often located near matrix-associated regions, we asked whether these sequences might also be involved in binding to the nuclear matrix. Indeed, DNA fragments containing the -500 binding site were bound by nuclear matrix proteins. Furthermore, UV cross-linking studies showed that the DNA binding site for interleukin-5-plus-antigen-inducible proteins could also bind to proteins solubilized from the nuclear matrix. Nuclear matrix-associated sequences have also been demonstrated on either side of the intronic immunoglobulin heavy chain enhancer. Our data suggest a topological model by which interactions among proteins bound to the promoter and distal enhancer sequences might occur. PMID- 1922041 TI - In vivo analysis of the Saccharomyces cerevisiae centromere CDEIII sequence: requirements for mitotic chromosome segregation. AB - In the yeast Saccharomyces cerevisiae, the complete information needed in cis to specify a fully functional mitotic and meiotic centromere is contained within 120 bp arranged in the three conserved centromeric (CEN) DNA elements CDEI, -II, and III. The 25-bp CDEIII is most important for faithful chromosome segregation. We have constructed single- and double-base substitutions in all highly conserved residues and one nonconserved residue of this element and analyzed the mitotic in vivo function of the mutated CEN DNAs, using an artificial chromosome. The effects of the mutations on chromosome segregation vary between wild-type-like activity (chromosome loss rate of 4.8 x 10(-4)) and a complete loss of CEN function. Data obtained by saturation mutagenesis of the palindromic core sequence suggest asymmetric involvement of the palindromic half-sites in mitotic CEN function. The poor CEN activity of certain single mutations could be improved by introducing an additional single mutation. These second-site suppressors can be found at conserved and nonconserved positions in CDEIII. Our suppression data are discussed in the context of natural CDEIII sequence variations found in the CEN sequences of different yeast chromosomes. PMID- 1922042 TI - Overexpression of transforming growth factor-beta in transgenic mice carrying the human T-cell lymphotropic virus type I tax gene. AB - Human T-cell lymphotropic virus type I (HTLV-I) has been associated with an adult form of T-cell leukemia as well as tropical spastic paraparesis, a neurodegenerative disease. Adult T-cell leukemia patients express high levels of the type 1 isoform of transforming growth factor-beta (TGF-beta 1), which is mediated by the effects of the HTLV-I Tax transactivator protein on the TGF-beta 1 promoter. To understand further the regulation of TGF-beta 1 expression by Tax, we examined its expression in transgenic mice carrying the HTLV-I tax gene. We show that tumors from these mice and other tissues, such as submaxillary glands and skeletal muscle, which express high levels of tax mRNA selectively express high levels of TGF-beta 1 mRNA and protein. Moreover, TGF-beta 1 significantly stimulated the incorporation of tritiated thymidine into one of three cell lines derived from neurofibromas of tax-transgenic mice, which suggests that the excessive production of TGF-beta 1 may play a role in tumorigenesis and that these mice may serve as a useful model for studying the biological effects of TGF beta in vivo. PMID- 1922043 TI - LyF-1, a transcriptional regulator that interacts with a novel class of promoters for lymphocyte-specific genes. AB - We have studied transcriptional control of the murine terminal deoxynucleotidyltransferase (TdT) gene, which is activated specifically in immature B and T lymphocytes. This analysis has led to the identification and purification of a 50-kDa sequence-specific DNA-binding protein, LyF-1, that interacts with the approximate consensus sequence PyPyTGGGAGPu and is enriched in cells at most stages of B- and T-cell differentiation. LyF-1 binds tightly to an element in the TdT promoter that we show is required for transcription in lymphocytes. LyF-1 also interacts with an element in the immunoglobulin mu enhancer, called microB, that was recently shown to be important for lymphocyte specific enhancer activity. Moreover, LyF-1 binds to the promoters for the lymphocyte-specific genes lambda 5, VpreB, and lck, all of which we speculate have additional features in common with the TdT promoter. Thus, LyF-1 may be a general transcriptional activator for genes whose expression is restricted to the B- and/or T-lymphocyte lineages. PMID- 1922044 TI - Amplification of the multidrug resistance gene pfmdr1 in Plasmodium falciparum has arisen as multiple independent events. AB - The multidrug resistance (MDR) phenotype in mammalian tumor cells can involve amplification of mdr genes that results in overexpression of the protein product termed P-glycoprotein. Chloroquine resistance (CQR) in Plasmodium falciparum has similarities with the MDR phenotype in tumor cells, and some isolates of P. falciparum have amplified levels of the pfmdr1 gene. To investigate the nature and origin of pfmdr1 amplicons, we have cloned large regions of a 110-kb amplicon from the CQR cloned isolate B8 by using the yeast artificial chromosome system. We have identified and sequenced the breakpoints of the amplicon by a novel method employing inverted polymerase chain reaction that is applicable to analysis of any large-scale repeat. We show that the five copies of the amplicon in this isolate are in a head to tail configuration. A string of 30 A's flank the breakpoints on each side of the amplified segment, suggesting a mechanism for the origin of the tandem amplification. Polymerase chain reaction analysis with oligonucleotides that cross the B8 breakpoint has shown in 26 independent CQR isolates, 16 of which contain amplified copies of pfmdr1, that amplification of the pfmdr1 gene in P. falciparum has arisen as multiple independent events. These results suggest that this region of the genome is under strong selective pressure. PMID- 1922045 TI - RNA polymerase II pauses at the 5' end of the transcriptionally induced Drosophila hsp70 gene. AB - An RNA polymerase II molecule is associated with the 5' end of the Drosophila melanogaster hsp70 gene under non-heat shock conditions. This polymerase is engaged in transcription but has paused, or arrested, after synthesizing about 25 nucleotides (A. E. Rougvie and J. T. Lis, Cell 54:795-804, 1988). Resumption of elongation by this paused polymerase appears to be the rate-limiting step in hsp70 transcription in uninduced cells. Here we report results of nuclear run-on assays that measure the distribution of elongating and paused RNA polymerase molecules on the hsp70 gene in induced cells. Pausing of polymerase was detected at the 5' end of hsp70 in cells exposed to the intermediate heat shock temperatures of 27 and 30 degrees C. At 30 degrees C, each copy of hsp70 was transcribed approximately five times during the 25-min heat shock that we used. Therefore, once the hsp70 gene is induced to an intermediate level, initiation of transcription by RNA polymerase II remains more rapid than the resumption of elongation by a paused polymerase molecule. PMID- 1922047 TI - Suppression of the chemically transformed phenotype of BHK cells by a human cDNA. AB - Transformation of the baby hamster kidney cell line BHK SN-10 by chemical carcinogens such as nitrosylmethylurea (NMU) is mediated by the loss of a gene product critical for the suppression of malignant transformation. Somatic cell hybrids between chemically transformed BHK SN-10 cells and either normal hamster kidney or human fibroblast cells are nontransformed; therefore, a recessive mechanism underlies the malignant transformation of BHK SN-10 cells after chemical carcinogenesis (A. Stoler and N. P. Bouck, Proc. Natl. Acad. Sci. USA 82:570-574, 1985). A human fibroblast cDNA library was constructed and introduced into NMU-transformed BHK SN-10 cells (NMU 34m) in order to identify a human cDNA capable of suppressing cellular transformation. NMU-transformed BHK cells were analyzed for reversion to an anchorage-dependent normal cellular phenotype after transfection with human cDNA. The human cDNA capable of inducing stable reversion of NMU 34m cells encodes the intermediate filament protein vimentin, which is apparently required for maintenance of the normal phenotype in BHK SN-10 cells. PMID- 1922046 TI - The chromatin structure of Saccharomyces cerevisiae autonomously replicating sequences changes during the cell division cycle. AB - The chromatin structures of two well-characterized autonomously replicating sequence (ARS) elements were examined at their chromosomal sites during the cell division cycle in Saccharomyces cerevisiae. The H4 ARS is located near one of the duplicate nonallelic histone H4 genes, while ARS1 is present near the TRP1 gene. Cells blocked in G1 either by alpha-factor arrest or by nitrogen starvation had two DNase I-hypersensitive sites of about equal intensity in the ARS element. This pattern of DNase I-hypersensitive sites was altered in synchronous cultures allowed to proceed into S phase. In addition to a general increase in DNase I sensitivity around the core consensus sequence, the DNase I-hypersensitive site closest to the core consensus became more nuclease sensitive than the distal site. This change in chromatin structure was restricted to the ARS region and depended on replication since cdc7 cells blocked near the time of replication initiation did not undergo the transition. Subsequent release of arrested cdc7 cells restored entry into S phase and was accompanied by the characteristic change in ARS chromatin structure. PMID- 1922048 TI - Yeast glycolytic mRNAs are differentially regulated. AB - The regulation of glycolytic genes in response to carbon source in the yeast Saccharomyces cerevisiae has been studied. When the relative levels of each glycolytic mRNA were compared during exponential growth on glucose or lactate, the various glycolytic mRNAs were found to be induced to differing extents by glucose. No significant differences in the stabilities of the PFK2, PGK1, PYK1, or PDC1 mRNAs during growth on glucose or lactate were observed. PYK::lacZ and PGK::lacZ fusions were integrated independently into the yeast genome at the ura3 locus. The manner in which these fusions were differentially regulated in response to carbon source was similar to that of their respective wild-type loci. Therefore, the regulation of glycolytic mRNA levels is mediated at the transcriptional level. When the mRNAs are ordered with respect to the glycolytic pathway, two peaks of maximal induction are observed at phosphofructokinase and pyruvate kinase. These enzymes (i) catalyze the two essentially irreversible steps on the pathway, (ii) are the two glycolytic enzymes that are circumvented during gluconeogenesis and hence are specific to glycolysis, and (iii) are encoded by mRNAs that we have shown previously to be coregulated at the translational level in S. cerevisiae (P. A. Moore, A. J. Bettany, and A. J. P. Brown, NATO ASI Ser. Ser. H Cell Biol. 49:421-432, 1990). This differential regulation of glycolytic mRNA levels might therefore have a significant influence upon glycolytic flux in S. cerevisiae. PMID- 1922049 TI - Cloning of a growth arrest-specific and transforming growth factor beta-regulated gene, TI 1, from an epithelial cell line. AB - By cDNA cloning and differential screening, five genes that are regulated by transforming growth factor beta (TGF beta) in mink lung epithelial cells were identified. A novel membrane protein gene, TI 1, was identified which was downregulated by TGF beta and serum in quiescent cells. In actively growing cells, the TI 1 gene is rapidly and transiently induced by TGF beta, and it is overexpressed in the presence of protein synthesis inhibitors. It appears to be related to a family of transmembrane glycoproteins that are expressed on lymphocytes and tumor cells. The four other genes were all induced by TGF beta and correspond to the genes of collagen alpha type I, fibronectin, plasminogen activator inhibitor 1, and the monocyte chemotactic cell-activating factor (JE gene) previously shown to be TGF beta regulated. PMID- 1922050 TI - Evidence suggesting that the ARS elements associated with silencers of the yeast mating-type locus HML do not function as chromosomal DNA replication origins. AB - The silent mating-type loci of Saccharomyces cerevisiae, HML and HMR, are flanked by transcriptional silencers that have ARS activity (i.e., they function as replication origins when in plasmids). To test whether these ARS elements are chromosomal origins, we mapped origins near HML (close to the left telomere of chromosome III). Our results indicate that the HML-associated ARS elements either do not function as chromosomal replication origins or do so at a frequency below our detection level, suggesting that replication from a silencer-associated origin in each S phase is not essential for the maintenance of transcriptional repression at HML. Our results also imply that the ability of a DNA fragment to function as an ARS element in a plasmid does not ensure its ability to function as an efficient chromosomal replication origin. Telomere proximity is not responsible for inactivating these ARS elements, because they are not detectably functional as chromosomal origins even in genetically modified strains in which they are far from the telomere. PMID- 1922051 TI - Exon recognition and nucleocytoplasmic partitioning determine AMPD1 alternative transcript production. AB - Two mature transcripts are produced from the rat AMP deaminase 1 (AMPD1) gene, one that retains exon 2 and one from which exon 2 has been removed. The ratio of these two transcripts is controlled by stage-specific and tissue-specific signals (I. Mineo, P. R. H. Clarke, R. L. Sabina, and E. W. Holmes, Mol. Cell. Biol. 10:5271-5278, 1990; R. L. Sabina, N. Ogasawara, and E. W. Holmes, Mol. Cell. Biol. 9:2244-2246, 1989). By using transfection studies with native, mutant, and chimeric minigene constructs, two steps in RNA processing that determine the ratio of these two transcripts have been identified. The first step is recognition of this exon in the primary transcript. The primary transcript is subject to alternative splicing in which exon 2 is either recognized and thereby included in the mature mRNA or is ignored and retained in a composite intron containing intron 1-exon 2-intron 2. The following properties of the primary transcript influence exon recognition. (i) Exon 2 is intrinsically difficult to recognize, possibly because of its small size (only 12 bases) and/or a suboptimal 5' donor site at the exon 2-intron 2 boundary. (ii) Intron 2 plays a permissive role in recognition of exon 2 because it is removed at a relatively slow rate, presumably because of the suboptimal polypyrimidine tract in the putative 3' branch site. The second step in RNA processing that influences the ratio of mature transcripts produced from the AMPD1 gene occurs subsequent to the ligation of exon 2 to exon 1. An RNA intermediate, composed of exon 1-exon 2-intron 2-exon 3, is produced in the first processing step, but it is variably retained in the nucleus. Retention of this intermediate in the nucleus is associated with accumulation of the mature mRNA containing exon 2, while cytoplasmic escape of this intermediate is reactions, exon recognition and nucleocytoplasmic partitioning, determine the relative abundance of alternative mRNAs derived from the AMPD1 gene. PMID- 1922052 TI - Heteroduplex formation and mismatch repair of the "stuck" mutation during mating type switching in Saccharomyces cerevisiae. AB - We sequenced two alleles of the MATa locus of Saccharomyces cerevisiae that reduce homothallic switching and confer viability to HO rad52 strains. Both the MATa-stk (J. E. Haber, W. T. Savage, S. M. Raposa, B. Weiffenbach, and L. B. Rowe, Proc. Natl. Acad. Sci. USA 77:2824-2828, 1980) and MATa-survivor (R. E. Malone and D. Hyman, Curr. Genet. 7:439-447, 1983) alleles result from a T----A base change at position Z11 of the MAT locus. These strains also contain identical base substitutions at HMRa, so that the mutation is reintroduced when MAT alpha switches to MATa. Mating-type switching in a MATa-stk strain relative to a MATa Z11T strain is reduced at least 50-fold but can be increased by expression of HO from a galactose-inducible promoter. We confirmed by Southern analysis that the Z11A mutation reduced the efficiency of double-strand break formation compared with the Z11T variant; the reduction was more severe in MAT alpha than in MATa. In MAT alpha, the Z11A mutation also creates a mat alpha 1 (sterile) mutation that distinguishes switches of MATa-stk to either MAT alpha or mat alpha 1-stk. Pedigree analysis of cells induced to switch in G1 showed that MATa-stk switched frequently (23% of the time) to produce one mat alpha 1-stk and one MAT alpha progeny. This postswitching segregation suggests that Z11 was often present in heteroduplex DNA that was not mismatch repaired. When mismatch repair was prevented by deletion of the PMS1 gene, there was an increase in the proportion of mat alpha 1-stk/MAT alpha sectors (59%) and in pairs of switched cells that both retained the stk mutation (27%). We conclude that at least one strand of DNA only 4 bp from the HO cut site is not degraded in most of the gene conversion events that accompany MAT switching. PMID- 1922053 TI - Cell-specific regulation of oncogene-responsive sequences of the c-fos promoter. AB - We have identified oncogene-responsive sequences in the human c-fos promoter that mediate induction of transcription by several nonnuclear oncoproteins and the tumor promoter TPA. These sequences are regulated in a cell-specific manner. (i) In NIH 3T3 cells, the CArG box of the c-fos promoter is sufficient to mediate activation by oncogenes. (ii) In contrast, in HeLa cells, additional flanking sequences are also required, including the outer arm of the serum response element and the FAP site. We also show that the serum response factor, which binds to the CArG box, activates transcription in vivo in NIH 3T3 cells but not in HeLa cells. Finally, we present evidence that the intracellular level of the c Fos protein could be a major determinant of cell-specific regulation of these oncogene-responsive elements of the c-fos promoter. PMID- 1922054 TI - Conserved mechanism of tRNA splicing in eukaryotes. AB - The ligation steps of tRNA splicing in yeast and vertebrate cells have been thought to proceed by fundamentally different mechanisms. Ligation in yeast cells occurs by incorporation of an exogenous phosphate from ATP into the splice junction, with concomitant formation of a 2' phosphate at the 5' junction nucleotide. This phosphate is removed in a subsequent step which, in vitro, is catalyzed by an NAD-dependent dephosphorylating activity. In contrast, tRNA ligation in vertebrates has been reported to occur without incorporation of exogenous phosphate or formation of a 2' phosphate. We demonstrate in this study the existence of a yeast tRNA ligase-like activity in HeLa cells. Furthermore, in extracts from these cells, the entire yeastlike tRNA splicing machinery is intact, including that for cleavage, ligation, and removal of the 2' phosphate in an NAD-dependent fashion to give mature tRNA. These results argue that the mechanism of tRNA splicing is conserved among eukaryotes. PMID- 1922055 TI - Androgen responsiveness of the murine beta-glucuronidase gene is associated with nuclease hypersensitivity, protein binding, and haplotype-specific sequence diversity within intron 9. AB - The tissue specificity and genetic variability of the murine beta-glucuronidase (GUS) response to androgen provide useful markers for identifying elements which underlie this responsiveness. While GUS is expressed constitutively in all examined cell types, kidney epithelial cells uniquely exhibit a manyfold yet slow rise in GUS mRNA and enzyme levels when stimulated by androgens. Three major phenotypes of this androgen response have been described among inbred strains of mice: (i) a strong response in strains of the Gusa haplotype, (ii) a reduced response in strains of the Gusb and Gush haplotypes, and (iii) no response, as observed in Gusor mice. These response variants define a cis-active element(s) which is tightly linked to the GUS structural gene. Nuclease hypersensitivity scans of kidney chromatin within and surrounding the structural gene revealed an androgen-inducible hypersensitive site in intron 9 of the gene in Gusa but not in Gusor mice. When a radiolabeled fragment of Gusa DNA containing this hypersensitive site was incubated with kidney nuclear extracts and then subjected to gel electrophoresis, two shifted bands were observed whose levels were dramatically higher in extracts of androgen-treated than in those of untreated Gusa mice. The shifted bands reflect binding of a kidney-specific factor(s) to a 57-bp region of complex dyad symmetry in Gusa and Gusor mice which is partially deleted in Gusb and Gush mice. This binding site is located approximately 130 bp downstream of a glucocorticoid response element sequence motif which is totally deleted in [Gus]or mice. Taken together, our results suggest that the androgen responsiveness of GUS in murine kidney epithelial cells is controlled by elements within the proximal end of intron 9 of the GUS structural gene. PMID- 1922056 TI - Expression of antisense RNA against initiation factor eIF-4E mRNA in HeLa cells results in lengthened cell division times, diminished translation rates, and reduced levels of both eIF-4E and the p220 component of eIF-4F. AB - HeLa cells were transformed to express antisense RNA against initiation factor eIF-4E mRNA from an inducible promoter. In the absence of inducer, these cells (AS cells) were morphologically similar to control cells but grew four- to sevenfold more slowly. Induction of antisense RNA production was lethal. Both eIF 4E mRNA and protein levels were reduced in proportion to the degree of antisense RNA expression, as were the rates of protein synthesis in vivo and in vitro. Polysomes were disaggregated with a concomitant increase in ribosomal subunits. Translation in vitro was restored by addition of the initiation factor complex eIF-4F but not by eIF-4E alone. Immunological analysis revealed that the p220 component of eIF-4F was decreased in extracts of AS cells and undetectable in AS cells treated with inducer, suggesting that p220 and eIF-4E levels are coordinately regulated. eIF-4A, another component of eIF-4F, was unaltered. PMID- 1922057 TI - Expression of CD44 is repressed in neuroblastoma cells. AB - We have used cDNA subtractive cloning to identify a group of human genes that are expressed in diverse differentiated derivatives of neural crest origin but not in neuroblastoma cell lines. One of these genes was identified as CD44, which encodes an integral membrane glycoprotein that serves as the principal receptor for hyaluronate and participates in specific cell-cell and cell-extracellular matrix interactions. The repression of CD44 expression in neuroblastoma cell lines might be relevant to their high metastatic potential. We have cloned full length cDNAs corresponding to CD44 trancscripts and identified a novel splice variant of CD44 lacking 31 amino acids of the extracellular domain. As a first step toward analysis of CD44 downregulation in neuroblastoma cells, we have mapped the CD44 RNA initiation site and analyzed the structure of the upstream regulatory region. We constructed a series of plasmids containing different amounts of CD44 upstream regulatory region linked to the bacterial chloramphenicol acetyltransferase gene and then analyzed their ability to promote transcription in neuroblastoma and melanoma cells. We found that a DNA segment including about 150 bp of the CD44 upstream region and the 5' end of the gene itself was sufficient to induce substantial transcription of the chloramphenicol acetyltransferase gene in both neuroblastoma and melanoma cells. Several upstream cis-acting elements contribute to the downregulation of CD44 in neuroblastoma cells, the most prominent being a 120-bp DNA fragment located 450 bp upstream to the RNA initiation site. Our data suggest that multiple factors might be involved in downregulation of CD44 in neuroblastoma cells. PMID- 1922058 TI - Galactokinase encoded by GAL1 is a bifunctional protein required for induction of the GAL genes in Kluyveromyces lactis and is able to suppress the gal3 phenotype in Saccharomyces cerevisiae. AB - We have analyzed a GAL1 mutant (gal1-r strain) of the yeast Kluyveromyces lactis which lacks the induction of beta-galactosidase and the enzymes of the Leloir pathway in the presence of galactose. The data show that the K. lactis GAL1 gene product has, in addition to galactokinase activity, a function required for induction of the lactose system. This regulatory function is not dependent on galactokinase activity, as it is still present in a galactokinase-negative mutant (gal1-209). Complementation studies in Saccharomyces cervisiae show that K. lactis GAL1 and gal1-209, but not gal1-r, complement the gal3 mutation. We conclude that the regulatory function of GAL1 in K. lactis soon after induction is similar to the function of GAL3 in S. cerevisiae. PMID- 1922059 TI - Structural characterization of SIL, a gene frequently disrupted in T-cell acute lymphoblastic leukemia. AB - The SIL (SCL interrupting locus) gene was initially discovered at the site of a genomic rearrangement in a T-cell acute lymphoblastic leukemia cell line. This rearrangement, which occurs in a remarkably site-specific fashion, is present in the leukemic cells of 16 to 26% of patients with T-cell acute lymphoblastic leukemia. We have now cloned a normal SIL cDNA from a cell line which does not carry the rearrangement. The SIL cDNA has a long open reading frame of 1,287 amino acids, with a predicted molecular size of 143 kDa. The predicted protein is not homologous with any previously described protein; however, a potential eukaryotic topoisomerase I active site was identified. Cross-species hybridization using a SIL cDNA probe indicated that the SIL gene was conserved in mammals. A survey of human and murine cell lines and tissues demonstrated SIL mRNA to be ubiquitously expressed, at low levels, in hematopoietic cell lines and tissues. With the exception of 11.5-day-old mouse embryos, SIL mRNA was not detected in nonhematopoietic tissues. The genomic structure of SIL was also analyzed. The gene consists of 18 exons distributed over 70 kb, with the 5' portion of the gene demonstrating alternate exon utilization. PMID- 1922060 TI - Both products of the fosB gene, FosB and its short form, FosB/SF, are transcriptional activators in fibroblasts. AB - We demonstrate that a member of the fos family, the fosB gene, gives rise to two transcripts by alternative splicing of exon 4, generating two proteins, FosB of 338 amino acids and a short form, FosB/SF, which contains the DNA binding and dimerization domains but not the 101 amino acids of the C terminus. FosB/SF activates an AP-1-chloramphenicol acetyltransferase construct in NIH 3T3 cells, as determined by transient and stable transfections, although more weakly than does FosB. In contrast to FosB, FosB/SF has lost its ability to repress the dyad symmetry element of the c-fos gene. FosB/SF when expressed in excess to FosB can downmodulate the activity of FosB. Constitutive expression of high levels of FosB/SF in NIH 3T3 cells has no significant inhibitory effect in the induction of cell proliferation or cell cycle progression, indicating that FosB/SF is not a negative regulator of cell growth. This conclusion is further confirmed by the observation that the majority of the Jun molecules are complexed with FosB/SF in the FosB/SF-overexpressing cells. PMID- 1922061 TI - Identification and characterization of a T-cell-specific enhancer adjacent to the murine CD4 gene. AB - Expression of the CD4 and CD8 glycoproteins is a tightly regulated process tied to the maturation of functionally distinct classes of thymocytes. Therefore, understanding of the mechanism of expression of the genes encoding CD4 and CD8 is likely to yield important insight into regulation of the differentiated functions of T cells. Here, we report the identification of a T-cell-specific enhancer in a DNase I-hypersensitive region about 13 kb 5' of the transcription initiation site of the murine CD4 gene. Within the minimal enhancer element, at least three nuclear protein binding sites were identified by DNase I footprint analysis. One site contains the consensus motif for TCF-1 alpha/LEF-1, a recently identified HMG box transcription factor primarily expressed in pre-B and T cells. By Southwestern (DNA-protein) blotting and binding competition analyses, the protein binding to this site was found to be indistinguishable from TCF-1 alpha/LEF-1. Mutagenesis of this site resulted in loss of factor binding but had a relatively minor effect on enhancer activity. In contrast, mutations in another site, containing two consensus binding motifs for basic helix-loop-helix proteins, abolished factor binding and dramatically reduced enhancer activity. None of the protein binding sites had activity on its own, suggesting that the CD4 enhancer requires the interaction of multiple regulatory sites. PMID- 1922062 TI - Cloning and expression of two human p70 S6 kinase polypeptides differing only at their amino termini. AB - Two classes of human cDNA encoding the insulin/mitogen-activated p70 S6 kinase have been isolated; the two classes differ only in the 5' region, such that the longer polypeptide (p70 S6 kinase alpha I; calculated Mr 58,946) consists of 525 amino acids, of which the last 502 residues are identical in sequence to the entire polypeptides encoded by the second cDNA (p70 S6 kinase alpha II; calculated Mr 56,153). Both p70 S6 kinase polypeptides predicted by these cDNAs are present in p70 S6 kinase purified from rat liver, and each is thus expressed in vivo. Moreover, both polypeptides are expressed from a single mRNA transcribed from the (longer) p70 S6 kinase alpha I cDNA through the utilization of different translational start sites. Although the two p70 S6 kinase polypeptides differ by only 23 amino acid residues, the slightly longer alpha I polypeptide exhibits anomalously slow mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), migrating at an apparent Mr of 90,000 probably because of the presence of six consecutive Arg residues immediately following the initiator methionine. Transient expression of p70 alpha I and alpha II S6 kinase cDNA in COS cells results in a 2.5- to 4-fold increase in overall S6 kinase activity. Upon immunoblotting, the recombinant p70 polypeptides appear as a closely spaced ladder of four to five bands between 65 and 70 kDa (alpha II) and 85 and 90 kDa (alpha I). Transfection with the alpha II cDNA yields only the smaller set of bands, while transfection with the alpha I cDNA generates both sets of bands. Mutation of Met-24 in the alpha I cDNA to Leu or Thr suppresses synthesis of the alpha II polypeptides. Only the p70 alpha I and alpha II polypeptides of slowest mobility on SDS-PAGE comigrate with the 70- and 90-kDa proteins observed in purified rat liver S6 kinase. Moreover, it is the recombinant p70 polypeptides of slowest mobility that coelute with S6 kinase activity on anion-exchange chromatography. The slower mobility and higher enzymatic activity of these p70 proteins is due to Ser/Thr phosphorylation, inasmuch as treatment with phosphatase 2A inactivates kinase activity and increases the mobility of the bands on SDS-PAGE in an okadaic acid-sensitive manner. Thus, the recombinant p70 S6 kinase undergoes multiple phosphorylation and partial activation in COS cells. Acquisition of S6 protein kinase catalytic function, however, is apparently restricted to the most extensively phosphorylated recombinant polypeptides. PMID- 1922063 TI - Identification of a conserved lipopolysaccharide-plus-interleukin-4-responsive element located at the promoter of germ line epsilon transcripts. AB - Treatment of splenic B lymphocytes and certain B-lineage cell lines with the mitogen lipopolysaccharide (LPS) and the lymphokine interleukin-4 (IL-4) induces expression of germ line immunoglobulin C epsilon transcripts and class switching to the C epsilon gene. We show that LPS-plus-IL-4 induction of germ line epsilon transcripts (termed I epsilon transcripts) occurs at the transcriptional level in an Abelson murine leukemia virus-transformed pre-B-cell line. A 1.1-kb region of DNA surrounding the I epsilon promoter endows inducible transcription to a heterologous reporter gene stably transfected into these cells; such inducible expression depends on combined treatment with LPS and IL-4. Analyses of constructs transiently introduced into a B-cell lymphoma line demonstrated that LPS-plus-IL-4-inducible expression can be conferred by a 179-bp segment of DNA spanning the I epsilon transcriptional initiation site. Mutational analyses demonstrated that this expression depended on DNA sequences within a conserved region directly upstream from the I epsilon transcriptional initiation region. One nuclear protein that is constitutively expressed in normal B cells binds to the downstream end of the conserved sequence; its binding specificity correlates with the functional effect of several mutations. Two additional proteins, which are induced by IL-4 treatment of splenic B cells, bind to the transcription initiation sites of I epsilon. These proteins are indistinguishable in binding assays from proteins previously shown to bind an enhancer region of the class II major histocompatibility complex gene A alpha. PMID- 1922064 TI - Intracisternal A-type particle-mediated activations of cytokine genes in a murine myelomonocytic leukemia: generation of functional cytokine mRNAs by retroviral splicing events. AB - Previously we have described the derivation of three distinct classes of leukemic cell clones from a single in vivo-passaged myelomonocytic leukemia, WEHI-274, that arose in a mouse infected with the Abelson leukemia virus/Moloney leukemia virus complex (K. B. Leslie and J. W. Schrader, Mol. Cell. Biol. 9:2414-2423, 1989). The three classes of cell clones were characterized by distinct patterns of growth in vitro, the production of cytokines, and the presence of cytokine gene rearrangements. However, all three classes of WEHI-274 clones bore a common rearrangement of the c-myb gene, suggesting that all were derived from the one ancestral cell and that at least three distinct and independent autostimulatory events were involved in the progression of a single myeloid leukemic disease. In this article, we demonstrate that the autocrine growth factor production by the WEHI-274 leukemic clones resulted from cytokine gene activations mediated by the insertion of an intracisternal A-type particle (IAP) sequence 5' to the interleukin-3 (IL-3) gene, in the case of the class I clone, or 5' to the gene for granulocyte-macrophage colony-stimulating factor (GM-CSF), in the case of the class II clones. IAPs are defective murine retroviruses encoded by endogenous genetic elements which may undergo transpositions and act as endogenous mutagens. The functional IL-3 and GM-CSF mRNAs were generated by mechanisms in which the splice donor apparatus of the IAP sequence has been used in IAP gag-to-IL-3 or GM-CSF splicing events. PMID- 1922065 TI - The CDC20 gene product of Saccharomyces cerevisiae, a beta-transducin homolog, is required for a subset of microtubule-dependent cellular processes. AB - Previous analysis of cdc20 mutants of the yeast Saccharomyces cerevisiae suggests that the CDC20 gene product (Cdc20p) is required for two microtubule-dependent processes, nuclear movements prior to anaphase and chromosome separation. Here we report that cdc20 mutants are defective for a third microtubule-mediated event, nuclear fusion during mating of G1 cells, but appear normal for a fourth microtubule-dependent process, nuclear migration after DNA replication. Therefore, Cdc20p is required for a subset of microtubule-dependent processes and functions at multiple stages in the life cycle. Consistent with this interpretation, we find that cdc20 cells arrested by alpha-factor or at the restrictive temperature accumulate anomalous microtubule structures, as detected by indirect immunofluorescence. The anomalous microtubule staining patterns are due to cdc20 because intragenic revertants that revert the temperature sensitivity have normal microtubule morphologies. cdc20 mutants have a sevenfold increase in the intensity of antitubulin fluorescence in intranuclear spindles compared with spindles from wild-type cells, yet the total amount of tubulin is indistinguishable by Western immunoblot analysis. This result suggests that Cdc20p modulates microtubule structure in wild-type cells either by promoting microtubule disassembly or by altering the surface of the microtubules. Finally, we cloned and sequenced CDC20 and show that it encodes a member of a family of proteins that share homology to the beta subunit of transducin. PMID- 1922066 TI - Id proteins Id1 and Id2 selectively inhibit DNA binding by one class of helix loop-helix proteins. AB - The DNA binding activities of some basic region and putative helix-loop-helix (bHLH)-containing transcriptional factors can be inhibited by the Id protein. Because Id contains the HLH motif for dimerization but not the basic amino acid region for DNA binding, heterodimers of Id with bHLH transcriptional factors may not bind to DNA. We have isolated and characterized the gene and cDNA clones for a new Id protein, designated Id2. The Id2 protein contains a helix-loop-helix motif similar to that of the previously described Id protein (referred to here as Id1), but the two proteins are different elsewhere. Id1 and Id2 are encoded by two unlinked genes, as shown by chromosome mapping. The two Id proteins have similar inhibitory activities. They selectively bind to and inhibit the function of one set of bHLH proteins, typified by E2A.E47 and E2B.m3, but not that of the other set, including TFE3, USF, and AP4. The Id proteins also homodimerize poorly. Expression of both Id genes is down-regulated during differentiation in a variety of cell types. PMID- 1922067 TI - The intron-containing hsp82 gene of the dimorphic pathogenic fungus Histoplasma capsulatum is properly spliced in severe heat shock conditions. AB - We have isolated and characterized a heat-inducible gene, hsp82, from the dimorphic pathogenic fungus Histoplasma capsulatum, which is a filamentous mold at 25 degrees C and a unicellular yeast at 37 degrees C. This gene, which has a high degree of homology with other members of the hsp82 gene family, is split into three exons and two introns of 122 and 86 nucleotides, respectively. Contrary to what has been demonstrated in Drosophila melanogaster, Saccharomyces cerevisiae, and other organisms, hsp82 mRNA in H. capsulatum is properly spliced during the severe heat conditions of 37 to 40 degrees C in the temperature sensitive Downs strain. Splicing accuracy was also observed at 42 degrees C in the temperature-tolerant G222B strain, which showed no evidence of accumulation of primary transcripts. Furthermore, the intron containing the beta-tubulin gene is also properly spliced at the upper temperature range, suggesting that the lack of a block in splicing may be a general phenomenon in this organism. PMID- 1922068 TI - A synthetic silencer mediates SIR-dependent functions in Saccharomyces cerevisiae. AB - Copies of the mating-type genes are present at three loci on chromosome III of the yeast Saccharomyces cerevisiae. The genes at the MAT locus are transcribed, whereas the identical genes at the silent loci, HML and HMR, are not transcribed. Several genes, including the four SIR genes, and two sites, HMR-E and HMR-I, are required for repression of transcription at the HMR locus. Three elements have been implicated in the function of the HMR-E silencer: a binding site for the RAP1 protein, a binding site for the ABF1 protein, and an 11-bp consensus sequence common to nearly all autonomously replicating sequence (ARS) elements (putative origins of DNA replication). RAP1 and ABF1 binding sites of different sequence than those found at HMR-E were joined with an 11-bp ARS consensus sequence to form a synthetic silencer. The synthetic silencer was able to repress transcription of the HMRa1 gene, confirming that binding sites for RAP1 and ABF1 and the 11-bp ARS consensus sequence were the functional components of the silencer in vivo. Mutations in the ABF1 binding site or in the ARS consensus sequence of the synthetic silencer caused nearly complete derepression of transcription at HMR. The ARS consensus sequence mutation also eliminated the ARS activity of the synthetic silencer. These data suggested that replication initiation at the HMR-E silencer was required for establishment of the repressed state at the HMR locus. PMID- 1922069 TI - Nonhomologous recombination at sites within the mouse JH-C delta locus accompanies C mu deletion and switch to immunoglobulin D secretion. AB - Plasma cells secrete immunoglobulins other than immunoglobulin M (IgM) after a deletion and recombination in which a portion of the immunoglobulin heavy-chain locus (IgH), from the 5'-flanking region of the mu constant-region gene (C mu) to the 5'-flanking region of the secreted heavy-chain constant-region gene (CH), is deleted. The recombination step is believed to be targeted via switch regions, stretches of repetitive DNA which lie in the 5' flank of all CH genes except delta. Although serum levels of IgD are very low, particularly in the mouse, IgD secreting plasmacytomas of BALB/c and C57BL/6 mice are known. In an earlier study of two BALB/c IgD-secreting hybridomas, we reported that both had deleted the C mu gene, and we concluded that this deletion was common in the normal generation of IgD-secreting cells. To learn how such switch recombinations occur in the absence of a switch region upstream of the C delta 1 exon, we isolated seven more BALB/c and two C57BL/6 IgD-secreting hybridomas. We determined the DNA sequences of the switch recombination junctions in eight of these hybridomas as well as that of the C57BL/6 hybridoma B1-8. delta 1 and of the BALB/c, IgD-secreting plasmacytoma TEPC 1033. All of the lines had deleted the C mu gene, and three had deleted the C delta 1 exon in the switch recombination event. The delta switch recombination junction sequences were similar to those of published productive switch recombinations occurring 5' to other heavy-chain genes, suggesting that nonhomologous, illegitimate recombination is utilized whenever the heavy-chain switch region is involved in recombination. PMID- 1922070 TI - Assembly of 60S ribosomal subunits is perturbed in temperature-sensitive yeast mutants defective in ribosomal protein L16. AB - Temperature-sensitive mutants defective in 60S ribosomal subunit protein L16 of Saccharomyces cerevisiae were isolated through hydroxylamine mutagenesis of the RPL16B gene and plasmid shuffling. Two heat-sensitive and two cold-sensitive isolates were characterized. The growth of the four mutants is inhibited at their restrictive temperatures. However, many of the cells remain viable if returned to their permissive temperatures. All of the mutants are deficient in 60S ribosomal subunits and therefore accumulate translational preinitiation complexes. Three of the mutants exhibit a shortage of mature 25S rRNA, and one accumulates rRNA precursors. The accumulation of rRNA precursors suggests that ribosome assembly may be slowed in this mutant. These phenotypes lead us to propose that mutants containing the rpl16b alleles are defective for 60S subunit assembly rather than function. In the mutant carrying the rpl16b-1 allele, ribosomes initiate translation at the noncanonical codon AUA, at least on the rpl16b-1 mRNA, bringing to light a possible connection between the rate and the fidelity of translation initiation. PMID- 1922071 TI - AAR2, a gene for splicing pre-mRNA of the MATa1 cistron in cell type control of Saccharomyces cerevisiae. AB - We have isolated a class of mutants, aar2, showing the alpha mating type due to a defect in a1-alpha 2 repression but with alpha 2 repression activity from a nonmater strain of Saccharomyces cerevisiae expressing both a and alpha mating type information in duplicate. Cells of the aar2 mutant and the aar2 disruptant also show a growth defect. A DNA fragment complementing the aar2 mutation contains an open reading frame consisting of 355 amino acid codons. Northern hybridization showed that cells of the aar2 mutant and disruptant contained alpha 1 and alpha 2 transcripts of the MAT alpha gene (or HML alpha in sir3 cells), but their a1 transcript of MATa (or HMRa in sir3 cells) migrated more slowly than that of the wild-type cells on gel electrophoresis and gave a diffused band. Primer extension analysis showed that the aar2 mutant and disruptant have a defect in splicing two short introns of the a1 pre-mRNA but not in splicing pre mRNA of ACT1. The alpha mating type, but not the slow-growing phenotype, of the aar2 mutant was suppressed by introduction of an intronless MATa1 DNA. Thus, the AAR2 gene is involved in splicing pre-mRNA of the a1 cistron and other genes that are important for cell growth. The AAR2 locus was mapped on chromosome II beside the SSA3 locus, with a 276-bp space, but was not allelic to either PRP5 or PRP6, which are both located on chromosome II and function in splicing pre-mRNA of ACT1. PMID- 1922072 TI - Analysis of the creA gene, a regulator of carbon catabolite repression in Aspergillus nidulans. AB - The complete nucleotide sequence derived from a genomic clone and two cDNA clones of the creA gene of Aspergillus nidulans is presented. The gene contains no introns. The derived polypeptide of 415 amino acids contains two zinc fingers of the C2H2 class, frequent S(T)PXX motifs, and an alanine-rich region indicative of a DNA-binding repressor protein. The amino acid sequence of the zinc finger region has 84% similarity to the zinc finger region of Mig1, a protein involved in carbon catabolite repression in yeast cells, and it is related both to the mammalian Egr1 and Egr2 proteins and to the Wilms' tumor protein. A deletion removing the creA gene was obtained, by using in vitro techniques, in both a heterokaryon and a diploid strain but was unobtainable in a pure haploid condition. Evidence is presented suggesting that the phenotype of such a deletion, when not complemented by another creA allele, is leaky lethality allowing limited germination of the spore but not colony formation. This phenotype is far more extreme than that of any of the in vivo-generated mutations, and thus either the gene product may have an activator activity as well as a repressor function or some residual repressor function may be required for full viability. PMID- 1922073 TI - Mutations in SPT16/CDC68 suppress cis- and trans-acting mutations that affect promoter function in Saccharomyces cerevisiae. AB - SPT16 was previously identified as a high-copy-number suppressor of delta insertion mutations in the 5' regions of the HIS4 and LYS2 genes of Saccharomyces cerevisiae. We have constructed null mutations in the SPT16 gene and have demonstrated that it is essential for growth. Temperature-sensitive-lethality spt16 alleles have been isolated and shown to be pleiotropic; at a temperature permissive for growth, spt16 mutations suppress delta insertion mutations, a deletion of the SUC2 upstream activating sequence, and mutations in trans-acting genes required for both SUC2 and Ty expression. In addition, SPT16 is identical to CDC68, a gene previously shown to be required for passage through the cell cycle control point START. However, at least some transcriptional effects caused by spt16 mutations are independent of arrest at START. These results and those in the accompanying paper (A. Rowley, R. A. Singer, and G. C. Johnston, Mol. Cell. Biol. 11:5718-5726, 1991) indicate that SPT16/CDC68 is required for normal transcription of many loci in S. cerevisiae. PMID- 1922074 TI - Structural and functional dissection of a membrane glycoprotein required for vesicle budding from the endoplasmic reticulum. AB - Sec12p is a membrane glycoprotein required for the formation of a vesicular intermediate in protein transport from the endoplasmic reticulum to the Golgi apparatus in Saccharomyces cerevisiae. Comparison of the N-linked glycosylation of Sec12p, a Sec12p-invertase hybrid protein, and a derivative of Sec12p lacking 71 carboxy-terminal amino acids showed that Sec12p is a type II membrane protein. Analysis of two truncated forms of Sec12p and of a temperature-sensitive mutant indicated that the C-terminal domain of Sec12p is not essential for protein transport, whereas the integrity and membrane attachment of the cytoplasmic N terminal domain are essential. Expression of a soluble cytoplasmic domain dramatically inhibited the growth of a sec12 temperature-sensitive strain by increasing the transport defect at a normally permissive temperature. This growth inhibition as well as the sec12 temperature-sensitive defect were suppressed by the overproduction of Sar1p, a small GTP-binding protein that participates in protein transport. Sar1p membrane association was enhanced by elevated levels of Sec12p. These results suggest that the cytoplasmic domain of Sec12p interacts with Sar1p and that the complex may function to promote vesicle formation. PMID- 1922075 TI - nirA, the pathway-specific regulatory gene of nitrate assimilation in Aspergillus nidulans, encodes a putative GAL4-type zinc finger protein and contains four introns in highly conserved regions. AB - The nucleotide sequence of nirA, mediating nitrate induction in Aspergillus nidulans, has been determined. Alignment of the cDNA and the genomic DNA sequence indicates that the gene contains four introns and encodes a protein of 892 amino acids. The deduced NIRA protein displays all characteristics of a transcriptional activator. A putative double-stranded DNA-binding domain in the amino-terminal part comprises six cysteine residues, characteristic for the GAL4 family of zinc finger proteins. An amino-terminal highly acidic region and two proline-rich regions are also present. The nucleotide sequences of two mutations were determined after they were mapped by transformation with overlapping DNA fragments, amplified by the polymerase chain reaction. nirA87, a mutation conferring noninducibility by nitrate and nitrite, has a -1 frameshift at triplet 340, which eliminates 549 C-terminal amino acids from the polypeptide. Under the assumption that the truncated polypeptide is stable, it comprises the zinc finger domain and the acidic region, which seem not sufficient for transcriptional activation. nirAd-106, an allele conferring nitrogen metabolite derepression of nitrate and nitrite reductase activity, includes two transitions, changing a glutamic acid to a lysine and a valine to an alanine, situated between a basic and a proline-rich region of the protein. Northern (RNA) analysis of the wild type and of constitutive (nirAc) and derepressed (nirAd) mutants show that the nirA transcript does not vary between these strains, being in all cases constitutively expressed. On the other hand, transcript levels of structural genes (niaD and niiA) do vary, being highly inducible in the wild type but constitutively expressed in the nirAc mutant. The nirAd mutant appears phenotypically derepressed, because the niaD and niiA transcript levels are overinduced in the presence of nitrate but are still partially repressed in the presence of ammonium. PMID- 1922076 TI - Heterogeneously initiated transcription from the pre-B- and B-cell-specific mb-1 promoter: analysis of the requirement for upstream factor-binding sites and initiation site sequences. AB - The mb-1 gene, encoding a membrane immunoglobulin-associated protein, is developmentally regulated and expressed specifically in pre-B and mature B lymphocytes. Analysis of the TATA-less mb-1 promoter indicated that it directs initiation of transcription from multiple sites. Promoter sequences between -68 and +70 conferred the correct pattern of cell type-specific transcription upon a heterologous gene. Two nuclear factor-binding sites that are important for promoter function were identified between -59 and -38. Both sites interacted with ubiquitous nuclear factors in vitro. One of these factors was identified as Sp1. Multimerized copies of both factor-binding sites augmented expression from a heterologous minimal promoter in both lymphoid and nonlymphoid cells, suggesting that additional mb-1 promoter sequences are involved in determining the correct cell type specificity. Analysis of the heterogeneity of transcription initiation indicated that a mutation which increased the distance between upstream sequences and the region of initiation resulted in the utilization of a novel set of initiation sites. Moreover, an insertion of a TATA element into the mb-1 promoter at -30 biased initiation of transcription to +1 but did not abolish the use of the other sites. Mutation of an initiator sequence homology encompassing one of the major initiation sites had only a minor effect on its utilization. From these data, we conclude that upstream factor-binding sites in the TATA-less mb-1 promoter define a region in which initiation of transcription occurs at multiple sites. PMID- 1922078 TI - Coordinate estrogen-regulated instability of serum protein-coding messenger RNAs in Xenopus laevis. AB - Estrogen causes the cytoplasmic destabilization of albumin and gamma-fibrinogen mRNA in Xenopus laevis liver. The purpose of the present study was to determine whether mRNA destabilization is a generalized phenomenon in response to estrogen, or whether this process is restricted to a particular class of mRNAs. To address this, we have expanded our bank of serum protein-coding cDNA clones to include transferrin, the second protein of inter-alpha-trypsin inhibitor and clone 12B, for which there is no mammalian homolog. Together with albumin and gamma fibrinogen, these represent more than 85% of the mRNAs encoding liver secreted proteins. Estrogen administration to male Xenopus or to liver explant cultures causes the generalized disappearance of all of these mRNAs. In contrast, estrogen has no effect on actin, ferritin, or poly(A)-binding protein mRNA, all of which encode intracellular proteins. We have previously demonstrated that albumin mRNA is degraded in both messenger ribonucleoprotein and polysome fractions. Sucrose gradient analysis demonstrates the same pattern for degradation of all other serum protein-coding mRNAs. Estrogen has no effect on the amounts or gradient distribution of actin, ferritin, or poly(A)-binding protein mRNA. We conclude that regulated destabilization of mRNAs encoding secreted proteins is a generalized phenomenon in response to estrogen stimulation of Xenopus liver. PMID- 1922077 TI - Mutations in a conserved region of RNA polymerase II influence the accuracy of mRNA start site selection. AB - A sensitive phenotypic assay has been used to identify mutations affecting transcription initiation in the genes encoding the two large subunits of Saccharomyces cerevisiae RNA polymerase II (RPB1 and RPB2). The rpb1 and rpb2 mutations alter the ratio of transcripts initiated at two adjacent start sites of a delta-insertion promoter. Of a large number of rpb1 and rpb2 mutations screened, only a few affect transcription initiation patterns at delta-insertion promoters, and these mutations are in close proximity to each other within both RPB1 and RPB2. The two rpb1 mutations alter amino acid residues within homology block G, a region conserved in the large subunits of all RNA polymerases. The three strong rpb2 mutations alter adjacent amino acids. At a wild-type promoter, the rpb1 mutations affect the accuracy of mRNA start site selection by producing a small but detectable increase in the 5'-end heterogeneity of transcripts. These RNA polymerase II mutations implicate specific portions of the enzyme in aspects of transcription initiation. PMID- 1922079 TI - Thyroid hormone decreases the stability and the poly(A) tract length of rat thyrotropin beta-subunit messenger RNA. AB - Thyroid hormone (T3 and T4) down-regulation of TSH subunit steady state mRNA levels and subunit gene transcription in vitro and in vivo has been well studied. We present evidence here that T3 can also regulate the turnover of TSH subunit mRNA. The apparent half-life of the TSH beta-subunit mRNA was determined by adding actinomycin-D (2 microM) to dispersed rat pituitary cultures in hypothyroid medium or medium containing 10(-7) M T3 and analyzing the decline in subunit mRNA levels with time. The half-life of the TSH beta mRNA from those cultures treated with T3 was shorter than that of the control cultures (9 vs. greater than 24 h, respectively). A possible mechanism by which TSH beta-subunit mRNA stability is altered is through a change in the size of each mRNA's poly(A) tail. Northern blot analysis of total RNA from the above cultures revealed that T3 treatment reduces the size of the TSH beta-subunit mRNA. To determine if this alteration of mRNA size was due to a loss of a portion of the poly(A) tract and not to alternative splicing of the transcript or use of a secondary transcriptional start site, pooled RNAs were hybridized with oligo(dT) and subsequently digested with RNAse-H to remove the poly(A) tract. RNA blot analysis of these RNAs showed that T3 treatment results in the loss of most of the TSH beta poly(A) tail.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922080 TI - Tissue-specific transcription initiation and effects of growth hormone (GH) deficiency on the regulation of mouse and rat GH-releasing hormone gene in hypothalamus and placenta. AB - Hypothalamic GRH gene expression has been shown to be negatively regulated by GH in both rat and mouse. The recent reports of different 5' untranslated sequences in mouse GRH cDNA from hypothalamus and placenta have raised the possibility of tissue-specific regulation of the GRH gene. To provide support for this possibility, we have studied rodent models with GH deficiency due to genetic defects in the pituitary. Complementary DNA probes for the hypothalamic and placental 5' regions were used to determine the tissue specificity of each mRNA. Although the hypothalamic form of GRH mRNA was detected in placenta, it constituted less than 0.7% of total placental GRH mRNA. A placental 5' probe (based on the previously reported sequence) hybridized only with a larger mRNA species and was not tissue specific, indicating that it was not related to GRH and was derived possibly from a cloning artifact. The correct 5' sequence of mouse placental GRH cDNA was determined and shown to be distinct from both that previously reported and the hypothalamic sequence. Although the placental form of GRH mRNA was detected in hypothalamus using the polymerase chain reaction, its levels were undetectable by Northern blotting. The 5' end of rat placental GRH cDNA was similarly sequenced and shown to exhibit no homology with the rat 5' hypothalamic sequence, but a high degree of homology with the corresponding mouse placental sequence. In GH-deficient dwarf (dw/dw) rats, hypothalamic GRH mRNA levels were significantly increased above control levels in both females and males, and pregnancy did not alter the levels in either (dw) or control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922081 TI - An essential role of domain D in the hormone-binding activity of human beta 1 thyroid hormone nuclear receptor. AB - By analogy with steroid receptors, human placental thyroid hormone nuclear receptor (hTR beta 1) could be divided into four functional domains: A/B (Met1 Leu101), C (Cys102-Ala170), D (Thr171-Lys237), and E (Arg238-Asp456). The E domain was thought to bind thyroid hormone. To evaluate whether domain E alone is sufficient to bind T3 or requires the presence of other domains for functional T3 binding activity, a series of deletion mutants was constructed. The mutants were expressed in Escherichia coli, and the expressed proteins were purified. Analysis of the T3-binding affinity and analog specificity of the purified truncated hTR beta 1 indicated that domain E alone did not have T3-binding activity. Extension of the amino-terminal sequence of domain E to include part of domain D yielded a mutant (Lys201-Asp456) with a Ka for T3 of 0.5 +/- 0.2 x 10(9) M-1. Further extension to include the entire domain D (Met169-Asp456) yielded a mutant with T3 binding activity with a Ka of 0.8 +/- 0.1 x 10(9) M-1. Further extension of the amino-terminal sequence to include domain C increased the affinity for T3 by nearly 2-fold (Ka = 1.5 +/- 0.4 x 10(9) M-1). The Ka for the wild-type hTR beta 1 is 1.5 +/- 0.2 x 10(9) M-1. Furthermore, mutant (Met169-Asp456) binds to 3',5',3 triiodo-L-thyropropionic acid, D-T3, L-T4, and L-T3 with 307%, 37%, 7%, and 0.1%, respectively, of the activity of L-T3. This order of analog affinity is similar to that of the wild-type hTR beta 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922082 TI - Differential translatability in vitro of multiple messenger RNAs encoding the beta-subunit of mouse thyrotropin. AB - The mouse TSH beta gene contains two start sites of transcription and exhibits alternative splicing among its first three exons, which encode 5'-untranslated mRNA sequences. Expression of the mouse TSH beta gene, therefore, gives rise to multiple mRNAs, each with a unique 5'-untranslated region. We have determined the relative translational efficiencies of these mRNAs in vitro, and we demonstrate that one of them directs the synthesis of a novel TSH beta presubunit. The four TSH beta mRNAs that are expressed from the down-stream transcription start site (TSS2) and the major mRNA derived from the up-stream start site (TSS1) were transcribed in vitro and translated in reticulocyte lysates and wheat germ extracts. The mRNA from TSS1 gave a novel TSH beta presubunit due to initiation of translation at an up-stream AUG unique to this mRNA. The novel presubunit contained a 17-amino acid NH2-terminal extension sequence, compared to the normal TSH beta presubunit, which is encoded by each of the mRNAs from TSS2. Despite the fact that the NH2-terminal extension sequence appeared to lack the characteristics of a signal peptide, the novel TSH beta presubunit was processed about 50% as efficiently by microsomal membranes as the normal presubunit, with glycosylation and cleavage by signal peptidase. There was an approximately 2-fold range in relative translatability among the different TSH beta mRNAs, and the mRNA encoding the novel TSH beta presubunit had the highest translational efficiency. Our data, therefore, suggest that the longer presubunit may be synthesized in vivo in significant amounts and give rise to a novel mature TSH beta subunit. PMID- 1922083 TI - Elevated transforming growth factor-beta 1 and beta 3 mRNA levels are associated with ras + myc-induced carcinomas in reconstituted mouse prostate: evidence for a paracrine role during progression. AB - Mouse prostate reconstitution is a useful model for studying the progression of ras + myc-induced carcinomas. When these oncogenes were introduced into both the epithelial and the mesenchymal compartments, poorly differentiated adenocarcinomas resulted. Restricted introduction of both oncogenes into the epithelium produced epithelial hyperplasia. Malignancies were produced in two out of 17 cases of selectively transformed epithelium, suggesting that the hyperplastic condition represents a premalignant phenotype. Restricted introduction of both oncogenes into the mesenchyme produced only mesenchymal dysplasia. Transforming growth factor-beta 1 (TGF-beta 1) and beta 3 (TGF-beta 3) mRNA levels were elevated in the ras + myc-induced carcinomas when compared to the normal controls or to the epithelial hyperplasias. In contrast, TGF-beta 2 mRNA levels were similar in all control and ras + myc-induced carcinomas. Elevated TGF-beta 1 mRNA levels were also found in mesenchymal dysplasia pointing to a potential paracrine activity by the ras + myc transformed mesenchyme. We conclude that elevated TGF-beta 1 and beta 3 are correlated with progression to malignancy and that mesenchyme derived TGF-beta 1 may play an important role in the promotion of ras + myc-induced carcinomas in this model system. PMID- 1922084 TI - Transcriptional regulation of the human transforming growth factor-alpha gene. AB - We and others have previously reported that transforming growth factor-alpha (TGF alpha) expression is hormonally responsive and its expression is coregulated with that of its receptor [the epidermal growth factor (EGF) receptor]. The 5' flanking region of the TGF alpha gene was characterized to determine whether it could confer hormone responsiveness to a reporter gene (luciferase) in human mammary carcinoma cells (MDA468). This segment of the gene is GC rich and contains an element strikingly similar to the core element of the EGF receptor gene that has been shown to mediate both basal and hormone-stimulated expression of the EGF receptor. We now report that a 313-basepair (bp) proximal element of the TGF alpha 5'-flanking region (-373 to -59 relative to the TGF alpha translation start codon) is capable of conferring responses to phorbol ester and EGF. This gene segment does not contain the EGF receptor gene homolog or potential AP-2-binding sites, suggesting that these elements are not necessary for basal and EGF- or phorbol ester-responsive TGF alpha gene expression. This 313-bp proximal element also confers proper transcriptional initiation to the chimeric TGF alpha-luciferase reporter construct, indicating it is the TGF alpha promoter. A 1.1-kilobase segment of the TGF alpha 5'-flanking region also confers retinoic acid, thyroid hormone, and glucocorticoid responsiveness despite the absence of recognizable steroid hormone receptor-binding sites. These hormones stimulate reporter expression 1.5- to 2-fold in a dose-dependent manner. Extension of the 5'-flanking region to -3500 results in marked suppression of reporter gene expression. These results indicate that the TGF alpha gene 5' flanking sequence contains the elements responsible for hormonal responsiveness of this gene and that these elements are distinct from those that regulate the expression of the EGF receptor gene. PMID- 1922085 TI - Thyrotropin-releasing hormone action on the prolactin promoter is mediated by the POU protein pit-1. AB - TRH is known to regulate transcription of the PRL gene in pituitary cells, but little is known about the mechanism involved. We have characterized TRH response elements (TRHREs) in the promoter region of the rat PRL gene and the gene proximal protein that transmits the TRH signal to these elements. Exposure of GH3 rat pituitary cells to TRH yielded a large specific stimulation of transient expression of a PRL-chloramphenicol acetyltransferase (PRL-CAT) construct containing the PRL promoter region [(-204)PRL-CAT]. Analysis of 5' deletions of this construct implied that regions -174/-113 and -75/+38 each contain a TRHRE. GH3 cell nuclear extracts are known to footprint four sites, termed, respectively, 1P-4P, on the PRL promoter region. The TRHRE between positions 75/+38 was identified as element 1P, residing at -63/-39, since two copies of a 1P oligodeoxynucleotide transferred a TRH response to either (-39)PRL-CAT or mouse metallothionein-CAT construct (-39)mMT-CAT. Similarly, the more proximal TRHRE may be element 3P, residing at -167/-144, since two copies of this element also transferred a TRH response to (-39)PRL-CAT. Binding of pit-1 to site 1P is known to be capable of activating pituitary cell-specific PRL gene expression. To investigate whether pit-1 can also transduce a TRH signal to this site, oligodeoxynucleotides were prepared corresponding to mutations in either or both of two consensus sequences in site 1P.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922086 TI - Effects of varying the position of thyroid hormone response elements within the rat growth hormone promoter: implications for positive and negative regulation by 3,5,3'-triiodothyronine. AB - The thyroid hormone response element (T3RE) of the rat GH (rGH) promoter is located at -188 to -165 relative to the mRNA start site (TSS). Similar sites have been identified in other genes regulated by T3. We have investigated some of these T3REs in positions within the rGH promoter to assess the relative influences of DNA-binding site and position on positive and negative regulation by T3. Synthetic oligonucleotides were used with sequences from the rGH T3RE and proposed negative T3REs (nT3RE) from the rat and human alpha-subunit and rat beta TSH genes. The nT3REs were placed in the background of the wild-type rGH promoter in two positions, at -55 and down-stream of the TSS, with up- and down-mutations of the rGH T3RE. Rat GH T3RE elements were placed 700 basepairs up-stream of a basal rGH promoter and some also at the -55 and TSS positions. Constructions were tested in a transient transfection assay in rat pituitary tumor cells. Two copies of the rGHPAL (palindromic T3RE) placed 700 basepairs up-stream of the rGH promoter conferred 10-fold T3 induction. In the -55 position, the rGHPAL increased T3 induction compared to that in controls, whereas a fragment from the rat and human alpha-subunit gene in the same position reduced induction. Negative T3REs from rat beta TSH and human alpha-subunit reduced T3 induction 50% when placed at the TSS position of a rGH promoter containing an up-mutant T3RE. The T3REPAL placed at the same site increased T3 induction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922087 TI - Differential regulation of rat insulin I and II messenger RNA synthesis: effects of fasting and cyproheptadine. AB - Rats and mice retain a duplicated insulin (I) gene. Because the duplicated gene shares only incomplete homology with the ancestral insulin (II) gene it may be regulated differently. In the studies presented here we measured changes in abundance of these distinct insulin mRNAs and their precursors in response to fasting and fasting plus a single dose of cyproheptadine, two experimental manipulations that cause changes in the level of total insulin mRNA in rats. Both diminished rat insulin II mRNA to a greater extent than rat insulin I mRNA. Rat insulin II mRNA comprised 41% of the total insulin mRNA in 0 h controls and decreased to 33% of the total insulin mRNA after a 10-h fast. Insulin II mRNA decreased to 26% of the total insulin mRNA 10 h after treatment with cyproheptadine. To determine whether these manipulations had effects on insulin mRNA synthesis, precursors for each of the two mRNAs were quantified. Fasting for 24 h had only small effects on insulin I mRNA precursor, but diminished rat insulin II pre-mRNA to 32% of the 0 h control values. One and a half hours after fasting plus cyproheptadine administration, pre-mRNA for rat insulin II levels had decreased to 38%, while rat insulin I pre-mRNA remained at levels present in 0 h controls. Levels of rat insulin I and II pre-mRNAs were both maximally depressed at 10 h, but rat insulin II pre-mRNA decreased to 3%, while rat insulin I pre-mRNA diminished to only 49% of controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922088 TI - In vitro binding of the purified hormone-binding subunit of the estrogen receptor to oligonucleotides containing natural or modified sequences of an estrogen responsive element. AB - Estrogen receptor (ER) was purified from calf uterus by immunoaffinity chromatography in the absence of the ligand. The purified ER consists of a mixture of monomer and homodimer forms of 67-kDa hormone-binding subunit (no 90 kDa heat shock protein is present). The purified ER was incubated with a 32P labeled 61-basepair oligonucleotide containing the sequence of the estrogen response element (ERE) of the Xenopus laevis A2 vitellogenin gene. DNA mobility shift assays showed formation of specific complexes of the ERE containing oligonucleotide with ER, formation which did not require and was not affected by estradiol or antiestrogenic molecules. Both the monomer and the dimer were equally able to interact with the ERE-containing oligonucleotide. Sucrose gradient experiments showed that only the ER monomer is able to interact with an oligonucleotide in which a single mutation destroyed the dyad symmetry of ERE. Multiple symmetric mutations which did not alter the dyad symmetry of ERE nevertheless totally destroyed the ability of the oligonucleotide to form complexes with either the monomeric or dimeric form of ER. These results suggest that ER is able to bind to ERE independently of the presence of estradiol or other proteins and, therefore, that estradiol does not act by modulating the ability of ER to bind to ERE on DNA. PMID- 1922089 TI - Androgen modulation of DNA-binding factors in the mouse kidney. AB - Transcription of the RP2 gene in the mouse kidney is induced by androgens. This induction is species specific within the genus Mus. For example, the gene responds to androgens in Mus domesticus, but is refractory to hormone in the distantly related species M. caroli. In the present report we have characterized DNA-binding factors that recognize the 5' flanking region of the RP2 gene. One factor (termed RPBF-1) binds a DNA fragment spanning the region between -157 and 311 relative to the transcriptional start site. RPBF-1 is present in kidney nuclear extracts from both control and androgen-treated M. domesticus as well as from control M. caroli; however, in the latter species a distinct factor (termed RPBF-2) is induced by androgens and replaces RPBF-1. The androgen-dependent replacement of RPBF-1 by RPBF-2 is specific to the kidney of M. caroli. DNase-1 footprinting analyses indicate that the two factors recognize distinct, yet overlapping, regions of the RP2 promoter: RPBF-1 binds the region between -247 and -269, while RPBF-2 binds the region between -265 and -290. The RPBF-2-binding site contains a sequence that is homologous to that recognized by nuclear factor 1 (NF-1), suggesting that RPBF-2 is a NF-1-like factor. This is supported by competition experiments with synthetic oligonucleotides corresponding to the NF-1 binding site within the adenovirus origin of replication. Thus, androgens can modulate, in a species- and tissue-specific manner, DNA-binding factors that recognize promoter regions of genes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922090 TI - Bromo-adenosine stimulates choriogonadotropin production in JAr and cytotrophoblast cells: evidence for effects on two stages of differentiation. AB - 8-Bromo-adenosine (8-Br-adenosine) stimulates CG production in the JAr choriocarcinoma cell line. Because production of the alpha and beta CG subunits is coupled to the differentiation state of the trophoblasts, we compared the effect of adenosine on CG synthesis in the choriocarcinoma cell line with that in cytotrophoblast cells isolated from normal human term placenta. 8-Br-adenosine stimulated CG production by 5- to 6-fold in both cell types, whereas 8-Br guanosine had no effect, demonstrating specificity for adenine-containing derivatives. The ratio of CG alpha to CG beta production in JAr cells was 2:1 in the absence or presence of 8-Br-adenosine, whereas in cytotrophoblasts the ratio was 14:1 in controls, but decreased to 3:1 with 8-Br-adenosine. The latter is attributed to an enhanced production of the beta-sub-unit. Immunocytochemistry revealed that CG alpha and CG beta were only expressed in about 4% of JAr cells, and 8-Br-adenosine stimulated the number of positive cells 2- to 4-fold. Since 8 Br-adenosine also inhibited the division of JAr cells, the data suggest that it stimulates CG expression by promoting exit of a population of the cells from the cell cycle. In nondividing placenta-derived cytotrophoblasts, 8-Br-adenosine affects a later step in the differentiation pathway, resulting in a greater effect on the beta- than the alpha-subunit. Thus, our data further support the hypothesis that regulation of CG biosynthesis is linked to differentiation of the trophoblast. PMID- 1922091 TI - Coordinate regulation of fibrinogen subunit messenger RNA levels by glucocorticoids in primary cultures of Xenopus liver parenchymal cells. AB - Fibrinogen synthesis is specifically induced by a synthetic glucocorticoid, dexamethasone, in primary liver parenchymal cell cultures of the frog Xenopus laevis. Here we demonstrate that this increase in the level of fibrinogen protein production is accompanied by an induction in the three mRNAs coding for the fibrinogen subunits, designated A alpha, B beta, and gamma. The stimulation of fibrinogen mRNA levels appears to be mediated by the glucocorticoid receptor, because 1) the dose-response relationship parallels the reported affinity of dexamethasone for the Xenopus glucocorticoid receptor; and 2) the induction is blocked by RU 486, a potent antiglucocorticoid. All three subunit mRNA levels are induced coordinately by the hormone. The response is characterized by a detectable increase as early as 2-4 h after dexamethasone addition, continuing to a final 10- to 30-fold increase over basal levels by 60 h. The induction is specific for the fibrinogen mRNAs; total cellular RNA content and the levels of other mRNAs are unaffected by the hormone. Dexamethasone-mediated stimulation of A alpha and B beta mRNA production occurs in the absence of protein synthesis, whereas increased production of gamma mRNA is completely blocked under the same conditions. Thus, the A alpha and B beta genes are probably regulated at least in part by direct transcriptional activation by glucocorticoid-receptor complexes. Induction of the gamma gene is dependent on newly synthesized or labile proteins, which could be required for either transcription or posttranscriptional processes. These data suggest that different proteins are involved in regulation of the three fibrinogen genes. PMID- 1922092 TI - Identification of protein contact sites within the glucocorticoid/progestin response element. AB - The glucocorticoid receptor (GR) and the progestin receptor (PR) bind specifically to a variety of DNA sequences, glucocorticoid/progestin response elements (GRE/PRE), located in the proximity of responsive gene promoters. Using the isolated recombinant GR DNA-binding domain (DBD), it has recently been shown that GR interacts with the GRE/PRE, a 15-basepair partially palindromic consensus sequence, as a dimer. In this study an investigation into the GR-GRE/PRE and PR GRE/PRE interaction has been performed using missing base contact analysis with the tyrosine aminotransferase GREII (TATII) and recombinant GR DBD as well as a fusion protein consisting of the PR DBD fused to Staph. aureus protein-A. GR and PR had identical base contact points, localized within two consecutive major grooves, binding to the same face of the DNA. Ethylation interference was also performed on the GR DBD-TATII interaction. The contact points with the backbone phosphate groups flank the contacts within the major groove for each of the two half-sites. Knowledge of the contact points within the DNA sequence together with the three-dimensional structure of the protein enables modelling of the protein DNA interaction. PMID- 1922093 TI - Latent forms of transforming growth factor-beta (TGF beta) derived from bone cultures: identification of a naturally occurring 100-kDa complex with similarity to recombinant latent TGF beta. AB - Transforming growth factor-beta (TGF beta) is produced by most tissues, including bone, as a complex that is biologically inert. Release of TGF beta homodimer from this latent complex is necessary for TGF beta to exert effects on target cells. Thus, the nature of the latent complex and the mechanisms responsible for TGF beta release are the key to understanding TGF beta actions. We have found that murine calvarial bone cultures secrete multiple latent forms of TGF beta. Using analytical chromatography and Western blot analysis, we have compared bone latent TGF beta with the previously characterized latent complex present in platelets and with simian TGF beta precursor, which is stably expressed in a latent form by Chinese hamster ovarian (CHO) cells. A major component of the bone material appears to be a latent complex of 100 kDa, consisting of mature TGF beta (25-kDa homodimer). Like the recombinant TGF beta precursor, it elutes from a Mono-Q fast pressure liquid chromatography anion exchange column at 0.2 M NaCl and shows a very similar banding pattern on Western blots. Thus, this bone complex closely resembles recombinant TGF beta precursor expressed in a latent form by CHO cells and differs from the naturally occurring platelet complex, which has an additional 135-kDa binding protein that is bound through disulfide bonds to the precursor proregion. Western blot analysis also indicates that, like CHO cells, which express recombinant TGF beta precursor, but unlike other cell types, the bone cultures secrete detectable amounts of uncleaved TGF beta precursor. The bone calvarial culture is the first example of a naturally occurring system that expresses the 100-kDa latent TGF beta complex. PMID- 1922094 TI - Two point mutations in the hormone-binding domain of the mouse glucocorticoid receptor that dramatically reduce its function. AB - Mouse lymphoma cell line W7M320b, a mutant WEH17 line, requires higher than normal concentrations of glucocorticoid to elicit the hormone responses that are characteristic of this lineage. Complementary DNA clones representing the glucocorticoid receptor (GR) mRNA were derived from the mutant cells, and the sequences coding for the hormone-binding domain were substituted for the analogous wild-type sequences in a GR cDNA expression vector. The function of the resulting GR proteins was tested by transient expression in COS-7 cells along with a glucocorticoid-inducible reporter gene in the presence of varying concentrations of glucocorticoid. From these assays and DNA sequence analyses, two independent functionally significant point mutations in the GR hormone binding domain were identified. A mutant GR protein containing the single amino acid substitution, Pro547 to Ala, was still functional as a transcriptional activator, but only at hormone concentrations 100 times higher than those required by the wild-type receptor. A second mutant GR protein with a Cys742 to Gly substitution was unstable and almost completely nonfunctional. PMID- 1922095 TI - Expression of human luteinizing hormone (LH) receptor: interaction with LH and chorionic gonadotropin from human but not equine, rat, and ovine species. AB - Studies on human LH receptors are difficult due to the limited availability of clinical samples. Recent cloning of rat and porcine LH receptor cDNAs indicated that these binding sites are single polypeptides of the G-protein-coupled receptor family with seven transmembrane domains. Based on the conserved sequences of rat and porcine receptors, we performed reverse transcription polymerase chain reaction, using human ovarian mRNA as template and obtained partial human LH receptor cDNA clones. Further screening of a human ovary cDNA library and subsequent ligation of individual cDNA clones generated a human LH receptor cDNA containing the entire amino acid-coding region. Sequence analysis indicated that the human receptor cDNA displays 89% and 82% homology at the nucleotide level with its porcine and rat counterparts, respectively. A region spanning the second extracellular and third transmembrane domains is highly conserved among the human LH, FSH, and TSH receptors. The ovarian LH receptor clone is, however, significantly different from an incompletely spliced LH receptor cDNA recently obtained from a human thyroid library. Unlike the thyroid clone, the ovarian LH receptor cDNA could be expressed in the human fetal kidney cell line (293), and radioligand receptor assay identified high affinity (Kd, 1.2 x 10(-10) M) LH/hCG-binding sites on the plasma membrane. Binding specificity of the human LH receptor was studied using recombinant human CG, LH, and FSH secreted by CHO cells transfected with the respective genes. Human CG and LH displaced [125I]hCG binding with an ED50 of 4.3 and 4.8 ng/ml, respectively. In contrast, recombinant FSH was not effective. Treatment of transfected cells with recombinant gonadotropins also induced dose-dependent increases in extracellular cAMP production (hCG = LH much greater than FSH; ED50 25, 10, and greater than 3000 ng/ml). Although equine, rat, and ovine LH as well as equine CG competed effectively for rat testicular LH receptor binding, these hormones were unable to displace [125I]hCG binding to the human receptor, suggesting evolutionary changes in receptor binding specificity and the importance of using human receptors for clinical studies. Thus, the cloning and expression of the human LH receptor cDNA allowed analysis of interactions between human LH receptor and gonadotropins from diverse species. The present work should provide the basis for future design of therapeutic agents capable of interacting with the human receptor and for understanding the structural basis for LH receptor binding to different gonadotropins. PMID- 1922096 TI - Gene structure of chum salmon somatolactin, a presumed pituitary hormone of the growth hormone/prolactin family. AB - From a chum salmon genomic DNA library, clones coding for somatolactin (SL), a presumed pituitary hormone belonging to the GH/PRL family, were isolated and analyzed. The salmon SL gene was 16 kilobases (kb) in length, this being the largest among mammalian GH (approximately 2 kb) and PRL (approximately 10 kb) and fish GH (approximately 4 kb) genes. As in the case of mammalian GH/PRL genes, the salmon SL gene was comprised of five exons in contrast to rainbow trout and Atlantic salmon GH genes, which each have six exons. Upstream from the transcriptional initiation site were found one TATA box identical to those of mammalian PRL genes and four consensus sequences corresponding to the Pit-1/GHF-1 binding element which is essential to the expression of mammalian GH and/or PRL genes. The similarity in amino acid sequences and organization of the SL gene with mammalian GH/PRL genes indicates that the SL gene is quite likely produced from an ancestral gene common to GH/PRL genes by gene duplication. Based on these considerations, an evolutionary model for the GH/PRL/SL gene family was made and shows the common ancestral gene to originate not from duplication of a primordial gene but from shuffling of independent exons and a regulatory sequence. PMID- 1922097 TI - Molecular cloning and expression of rat liver 3 alpha-hydroxysteroid dehydrogenase. AB - Complementary DNA clones encoding 3 alpha-hydroxysteroid dehydrogenase (3 alpha HSD) were isolated from a rat liver cDNA lambda gt11 expression library using monoclonal antibodies as probes. The sizes of the cDNA inserts ranged from 1.3 2.3 kilobases. Sequence analysis indicated that variation in the DNA size was due to heterogeneity in the length of 3' noncoding sequences. A full-length cDNA clone of 1286 basepairs contained an open reading frame encoding a protein of 322 amino acids with an estimated mol wt of 37 kDa. When expressed in E. coli, the encoded protein migrated to the same position on sodium dodecyl sulfate polyacrylamide gels as the enzyme purified from rat liver cytosols. The protein expressed in bacteria was highly active in androsterone reduction in the presence of NAD as cofactor, and this activity was inhibited by indomethacin, a potent inhibitor of 3 alpha HSD. The predicted amino acid sequence of 3 alpha HSD was related to sequences of several other enzymes, including bovine prostaglandin F synthase, human chlordecone reductase, human aldose reductase, human aldehyde reductase, and frog lens epsilon-crystalline, suggesting that these proteins belong to the same gene family. PMID- 1922098 TI - Structure-function analysis of the rat prolactin promoter: phasing requirements of proximal cell-specific elements. AB - Expression of PRL, a member of the GH family of genes, is restricted to the lactotroph cells of the anterior pituitary. The proximal promoter of the rat PRL (rPRL) gene contains four factor-binding sites. Three nonadjacent elements, footprints (FP) I, III, and IV, are separated by an integral number of helical turns and bind a pituitary-specific factor, LSF-1. FP II binds another factor present in pituitary and nonpituitary cells. The mechanisms by which DNA-bound proteins influence RNA polymerase-II activity over large distances are not fully understood, but protein-protein interactions, with looping of intervening DNA, may bring distant sites into close proximity. Here, we demonstrate, using protein titration studies, that LSF-1 binds to the most proximal FP I element with the highest affinity, whereas it binds the more distal elements, FP III and FP IV, with progressively lower affinities. Time-course and salt-sensitivity studies reveal that binding of LSF-1 to all three pituitary-specific rPRL promoter sites occurs rapidly (less than or equal to 1 min) and requires fairly high salt concentrations (greater than or equal to 300 mM KCl) to destabilize protein-DNA interactions. Moreover, once bound, the pituitary nuclear factor(s) induces a conformational change in rPRL DNA structure with greatly delayed kinetics (greater than 15 min) and at a different salt concentration than are required for simply factor binding. Taken together, these data suggest a model in which LSF-1 initially binds fairly rapidly to multiple nonadjacent elements and then interacts with itself or other DNA-bound proteins much more slowly, possibly looping or bending the rPRL promoter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922099 TI - Transcriptional activation by Nur77, a growth factor-inducible member of the steroid hormone receptor superfamily. AB - nur77 is a growth factor-inducible immediate early gene that encodes a protein with extensive sequence homology to members of the steroid/thyroid hormone receptor superfamily. By analogy to steroid receptors, the Nur77 protein is thought to act as a ligand-dependent transcription factor that regulates the genomic response to growth factors. Using chimeric gene constructs, we show that Nur77 can indeed function as a transcription activator. Furthermore, Nur77 chimeras can activate transcription in the absence of an exogenously added ligand. PMID- 1922100 TI - Expression of CA III in rodent models of obesity. AB - To achieve a better understanding of the biochemical basis of obesity, we have undertaken comparative analyses of adipose tissue of lean and obese mice. By two dimensional gel analysis, carbonic anhydrase-III (CA III) has been identified as a major constituent of murine adipose tissue. Quantitative comparisons of CA III protein and mRNA levels indicate that this enzyme is expressed at lower levels in adipose tissue from animals that were either genetically obese or had experimentally induced obesity compared to levels in the corresponding lean controls. This decrease in CA III expression was unique to adipose tissue, since other CA III-containing organs and tissues did not show a change when lean and obese animals were compared. Additionally, levels of CA III in adipose tissue from obese animals responded to acute changes in energy balance of the animal. These results are discussed in light of possible metabolic roles for CA III. PMID- 1922101 TI - Structural and functional analysis of the human IgG-Fab receptor activity of streptococcal protein G. AB - Streptococcal protein G (SPG) shows specific binding activity to IgGs and serum albumins from various species. In order to investigate the structural domains of SPG responsible for the specific interaction with human IgG-Fab, the binding characteristics of a collection of recombinant receptors were analysed. The study includes receptors comprising different parts of the SPG molecule as well as chimeric receptors containing IgG-binding domains of staphylococcal protein A (SPA) fused to the N-terminal AB-region of SPG, which has been claimed to interact with human IgG-Fab. Purified defined gene products were allowed to compete for the binding to human IgG, human IgG-F(ab')2 fragments and human serum albumin (HSA) in several sets of competitive binding experiments. The results demonstrate that the C-terminal C domains have both IgG-Fc- and IgG-Fab-binding capacities, whereas the N-terminal AB region is responsible for the HSA-binding only. These results, which are in conflict with previous work, demonstrate that the binding to both the IgG-Fc and the IgG-Fab region is mediated by the same structurally distinct receptor region of SPG. PMID- 1922102 TI - Molecular characterization of monoclonal anti-steroid antibodies: primary structures of the variable regions of seven antibodies specific for 17 alpha hydroxyprogesterone or 11-deoxycortisol and their pH-reactivity profiles. AB - The variable region nucleotide sequences of seven monoclonal anti-steroid antibodies that are specific for the closely related progesterone derivative, 11 deoxycortisol or 17 alpha-hydroxyprogesterone (17-OHP), have been determined by genomic cloning and DNA-sequencing or by direct mRNA-sequencing. As for their heavy chain variable regions, the nucleotide sequences of the SCET.M8.1 (SCET) and OHP 4B2.2.1 (4B2) antibodies were classified into the VH-9 family, while OHP 7D7.2.3 (7D7), 1E9.3.1 (1E9), 57.G6.1 (57) and 138.H8.1 (138) used VH-3 family genes. OHP 101.B11.1 (101) used a gene of the VH-1 family. For their light chain variable regions, SCET and 57 used VK-28 group genes, while 4B2, 7D7, 1E9, 101 and 138 antibodies used genes of the VK-21 subgroups (21A, 21B or 21C). All of the antibodies used different combinations of genes in the VH families and VK groups or subgroups. This indicates that the antibody response against the steroid hapten, 17-OHP, is fairly polyclonal, and several VH/VL combinations show high affinity for progesterone-related steroids. Although the primary structures of hypervariable loop regions of the mAbs were relatively diverse, generally, hydrophobic and aromatic amino acids were rich in these regions. Moreover, the length of heavy chain CDR3 was constant in all the antibodies investigated in this paper as well as the previously reported anti-progesterone monoclonal antibodies (mAbs). This suggests that the length of VH CDR3 in these mAbs has a considerable influence on the formation of antigen-combining pockets. The pH reactivity profiles for the anti-17-OHP mAbs indicated that the the steroid-mAb binding was independent of pH between pH 4 and 11 in most of the mAbs. The results suggest that the steroid-mAb interactions are not largely affected by the electrostatic environments near the combining sites of these mAbs. Taken together, these data imply that the shape of hydrophobic depressions in the combining sites is important for the binding of relatively large, hydrophobic and rigid haptens like steroids. PMID- 1922103 TI - Preferential binding and aggregation of rabbit C-reactive protein with arginine rich proteins. AB - Human and rabbit C-reactive proteins (CRP) are similar in mol. wt, structure and amino acid sequence. In addition to the characteristic phosphoryline (PC)-binding specificity, both CRP molecules bind arginine- and lysine-rich proteins. The human CRP-cationic protein reactivity has been reported to be inhibited by calcium and promoted by PC in the presence of calcium. The present study compares binding and precipitation reactions of rabbit CRP (raCRP) with arginine- and lysine-rich proteins, and demonstrates the differential modulation of these interactions by calcium and acidic pH. Rabbit CRP shows preferential binding and precipitation reactivities with arginine-rich cationic molecules. Binding of raCRP to poly-L-arginine (PLA) and arginine-rich histone (ARH) occurs at pH 6.0, in the presence of calcium and is inhibitable by phosphorylcholine (PC) suggesting an interaction at or near the calcium-modulated PC binding site. The in vitro precipitation of raCRP and arginine-rich cationic molecules is significantly inhibited at pH 6.0, by the non-precipitating lysine-rich ligand PLL, and by physiological levels of calcium, and may reflect the participation of distinct "self-aggregation" sites on CRP in the precipitation response. The significance of the preferential arginine reactivity of raCRP to in vivo functions as a scavenger of chromatin during cell death and/or as a modulator of lipoprotein metabolism during the acute phase response is discussed. PMID- 1922104 TI - Cell type and maturation stage-dependent polymorphism of N-linked oligosaccharides on murine lymphocytes and lymphoma cells. AB - We analyzed the overall structures of N-linked oligosaccharides on glycoproteins of various murine lymphocytic and lymphoma cells employing a newly developed method which was performed on high-performance liquid chromatography after derivatization of oligosaccharides with 2-aminopyridine. A total of 15 types of bi, tri- and tetra-antennary N-acetyllactosamine-type oligosaccharides with or without fucose and oligomannose-type oligosaccharides were identified on these cells in variable amounts depending on the type and maturation stage of the cells. It was found that all murine lymphocytic cells carry N-acetyllactosamine type oligosaccharides with the additional alpha-linked galactose residue on the non-reducing ends. Thymocytes had exceptionally large amounts of oligosaccharides with one or even two alpha-galactose residues per molecule. In contrast, peripheral resting T cells possessed those oligosaccharides only in a small amount, although the cells produced more the oligosaccharides after stimulation with Con A. Two thymoma lines such as BW 5147 and EL-4 and one B cell lymphoma line WEHI231 contained relatively large amount of oligosaccharides with alpha galactose residues. Significant change of the molar ratio of component carbohydrates by cell activation was observed also in oligommanose-type oligosaccharides which were few in resting T cells but were markedly increased in Con A activated cells. Molar ratio of triantennary oligosaccharides in total N acetyllactosamine type oligosaccharides was high in thymocytes and low in resting T cells, but was increased in T cells after Con A activation. It was also very high in WEHI 231 B cell lymphoma. Although BW 5147 and EL-4 thymoma did not contain tri-antennary oligosaccharides in high proportion, they carried larger tetra-antennary oligosaccharides with an N-acetyllactosamine repeating unit in definitive amounts. It is suggested from these results that overall structures of oligosaccharides on cell surface proteins of lymphocytes are finely controlled with link to cell differentiation, activation and transformation. PMID- 1922105 TI - Sequence of the bovine CD44 cDNA: comparison with human and mouse sequences. AB - CD44 is a cell-surface glycoprotein involved in leukocyte adherence, T-cell activation and lymphocyte homing. We have isolated and sequenced a cDNA clone which encodes for bovine CD44. The predicted amino acid sequence of bovine CD44 has an overall high similarity with that of human and mouse CD44, 79.5 and 73.2%, respectively. In all three species, CD44 has a similar transmembrane region and cytoplasmic tail. In addition, all of the cysteine residues and a majority of the putative N-linked glycosylation sites in the extracytoplasmic domain are conserved between bovine, human and mouse. All three species have an area of low interspecies similarity within the extracytoplasmic domain. This area has a similarity of 34% between bovine and human, 27% between bovine and mouse, and 35% between human and mouse. The location of this area of low similarity is conserved between species. PMID- 1922106 TI - Characterization of murine monoclonal antibodies against a repetitive synthetic peptide from the circumsporozoite protein of the human malaria parasite, Plasmodium falciparum. AB - Monoclonal antibodies (mAbs) were raised in mice against the synthetic peptide (NANP)40, consisting of 40 (NANP) repeats of the circumsporozoite (CS) protein of the human malaria parasite, Plasmodium falciparum, and characterized. (i) Five of these mAbs recognized the P. falciparum CS protein in western blot experiments and in immunofluorescence assays using different preparations of sporozoites. The remaining two mAbs (CT3.2 and CT3.3, both IgG1) gave negative results by both techniques. (ii) When the anti-(NANP)40 peptide mAbs were functionally tested in vitro to assess their ability to inhibit the attachment and penetration of the parasites into cultured human liver cells, six of them exhibited inhibitory activities ranging between 66 and 90%. CT3.2 mAbs, also, inhibited sporozoite attachment and penetration, despite the negative results by immunofluorescence and western blot experiments. However, when immunofluorescence was repeated in the presence of calcium, CT3.2 did reveal a positive recognition of P. falciparum sporozoites, suggesting that this mAb could recognize the (NANP) sequence when calcium was bound to the repetitive peptide. (iii) Furthermore, the binding of an anti-(NANP)40 IgM mAb (CT1) to the solid-phase peptide was not inhibited by preincubation of the peptide with a mAb against the P. falciparum CS protein. (iv) Finally, one anti-(NANP)40 IgG1 mAb (CT3.1) was unable to bind to the shorter (NANP)3 peptide, although it recognized the (NANP)40 peptide and the P. falciparum CS protein. The results presented here suggest that heterogeneous antibody populations are produced upon immunization of mice with (NANP)40 synthetic peptide and that epitopes different from those simply related to the linear (NANP) amino acid sequence are likely to be present in long (NANP)n constructs as well as in the repetitive domain of the P. falciparum CS protein. PMID- 1922107 TI - Cytoplasts from cytotoxic T lymphocytes are resistant to perforin-mediated lysis. AB - Cytotoxic T lymphocytes (CTL) contain a potent cytolytic pore-forming protein (PFP, perforin or cytolysin) localized in their cytoplasmic granules. In the presence of calcium, perforin lyses a variety of target cells (TC) non specifically. CTL, however, are generally resistant to the lytic effect of perforin. In this work, cytoplasts from CTL and susceptible TC were made by centrifuging cells on a Ficoll density gradient in the presence of cytochalasin B. Characterization by electron microscopy and a serine esterase assay established that both CTL and TC cytoplasts were completely devoid of nuclei and CTL cytoplasts contained essentially no granules. CTL cytoplasts are just as resistant to perforin-mediated lysis as the intact CTL, and both TC and their corresponding cytoplasts are very sensitive to lysis. Furthermore, CTL cytoplasts are less effective than TC cytoplasts in inhibiting hemolysis, a property shared by the respective intact cells. These results indicate that soluble granular components do not confer resistance on CTL, and suggest that the protective agent(s) acts by impeding perforin binding to the CTL membrane. PMID- 1922109 TI - Isolation and characterization of a T lymphocyte mutant defective in the protein kinase C signal transduction pathway. AB - The phorbol ester TPA is a potent protein kinase C (PKC) activator and a cofactor in the activation of the human Jurkat leukemic T cell line. We have studied the implication of the PKC signaling pathway in the process of T cell activation by generating TPA resistant mutants of Jurkat. These mutants were obtained by recovery of cells that survived a growth arrest induced by TPA. Several cellular phenomena dependent on TPA were dramatically altered in the mutated cells. The mutants were unable to form homoaggregates upon TPA stimulation. Moreover, they did not produce interleukin-2 after activation through engagement of the T cell receptor, in the presence of TPA. These results suggest that the PKC signaling pathway activated by TPA is defective in these cells. In an attempt to define and locate the defect present in the mutants, we have analysed the biochemical properties of PKC, the cellular receptor of TPA. The increase in kinase activity and the translocation of the enzyme to the plasma membrane after stimulation by TPA appeared to be normal in the mutants. We hypothesize that a metabolic step, critical for the completion of T cell activation, distinct from protein kinase C, is impaired in the mutant cells. PMID- 1922108 TI - Construction and expression of antibody-tumor necrosis factor fusion proteins. AB - The construction, expression and secretion of two genetically engineered antibody cytokine hybrid fusion proteins is described. To target tumor necrosis factor (TNF) to tumor cells, recombinant antibody techniques were used to generate F(ab')2-like antibody-TNF fusion proteins. At the gene level, an antitransferrin receptor antibody heavy chain gene was linked to a synthetic gene coding for human TNF. The chimeric heavy chain-TNF genes were introduced into a light chain secreting transfectoma cell line, which was producing the light chain of the same antibody. Cell lines were isolated which secreted antibody-TNF fusion proteins of expected size and composition. Culture supernatant of these cell lines contained TNF cytotoxic activity towards murine L929 cells and human MCF-7 cells, indicating that TNF is still active in the fusion protein constructs. These results illustrate the feasibility of the antibody engineering technology to create and produce chimeric mouse-human immunotoxin-like molecules. Furthermore, they demonstrate the ability of mammalian (myeloma) cells to express and secrete antibody-cytokine hybrid molecules with potential use in anticancer therapy. PMID- 1922110 TI - Correlation between the human and porcine complement system: a small-angle scattering study of cross immunity and methylamine-induced conformational changes of porcine C3 and C4 proteins. AB - The porcine complement proteins C3 and C4 have been isolated and then characterized using small-angle scattering methods. Within the limits of experimental errors, the porcine proteins are virtually identical with the corresponding human proteins as measured in terms of mol. wt, Mr and radius of gyration, R,: Mr(C3) = 198,000, Mr(C4) = 207,000, and R(C3) = 4.4 nm, R(C4) = 4.5 nm. The C3 and C4 proteins from pigs show cross-immunity with monoclonal antibodies (mAbs) raised against human C3 and C4, respectively. Using the Fab fragments of these mAbs as markers, it is indicated that porcine C3 and C4 undergo a conformational change after reaction with methylamine. The relatively large increase in the radius of gyration observed, delta R = 1.0-1.2 nm, going from the Fab complexes to the Fab complexes of the methylamine derivatives, is similar to that observed for human C3 under similar conditions. This may indicate that methylamine cleaves a labile thiol ester bond supposed to be present within the porcine proteins and that the epitopes interacting with the Fab fragments are very similar to those of the human proteins. Porcine C3 also resembles the human analogue by forming dimers after being subjected to methylamine and dilute lauryl sulphate: Mr = 404,000 and R = 7.9 nm. PMID- 1922111 TI - Subtype-specificity of antipeptide antibodies raised against unique sequences of human interferons-alpha. AB - A strategy for the production of human interferon-alpha (IFN-alpha) subtype specific antibodies, based on immunizing rabbits with short unique synthetic peptides coupled to protein carriers, has been validated. These peptides correspond to amino acid residues 99-111 of IFN-alpha 1, 50-57 and 103-116 of IFN alpha 2, and 37-50 of IFN-alpha 4. The antipeptide antibodies [anti-IFN alpha 1(99-111), anti-IFN alpha 2(50-57C), anti-IFN alpha 2(103-116) and anti-IFN alpha 4(C37-50)] were tested by ELISA and Western blotting for their reactivity with immunoaffinity-purified recombinant human IFN-alpha 1, -alpha 2b and -alpha 4a. The anti-IFN alpha 1(99-111) and anti-IFN alpha 2(50-57C) reacted with their corresponding IFN-alpha and did not crossreact with the other IFN subtypes. The anti-IFN alpha 2(103-116) reacted with IFN-alpha 2b and also crossreacted slightly with the other subtypes. The anti-IFN alpha 4(C37-50) reacted well with IFN-alpha 4a, crossreacted with significantly lower affinity with IFN-alpha 1 and did not bind IFN-alpha 2b. Residues 104-107 and 108-111 are the major components of the epitopes recognized by anti-IFN alpha 1(99-111) and anti-IFN alpha 2(103 116), respectively, as determined by ELISA against overlapping octapeptides. PMID- 1922112 TI - Light chain heterogeneity in the amphibian Xenopus. AB - Three subpopulations of light chains in Xenopus can be distinguished by monoclonal antibodies as well as by electrophoretic mobility on SDS-PAGE, peptide map and cell surface distribution. Analysis of these proteins from LPS-stimulated lymphocytes culture supernatants by two-dimensional gel electrophoresis showed a heterogeneity comparable to that observed for mouse kappa light chains. However, evidence from the selective expression of light chain subpopulations, as well as highly restricted light chain representation in anti-DNP antibodies, supports earlier findings that an antibody response in Xenopus is greatly limited in heterogeneity. PMID- 1922113 TI - Adaptation of the Muller method to allow quantitative characterization of the affinity and cross-reactivity of antibodies by competitive radioimmunoassay. AB - A quantitative expression is derived for the evaluation of antigen-antibody affinity constants from radioimmunoassays for the completely general situation in which antigen and antibody are both multivalent. The theoretical analysis is then extended to encompass quantitative characterization of the competitive inhibition observed in screening tests for cross-reactivity of antibody with structural analogs of the eliciting antigen. These procedures are illustrated with a radioimmunological study of the cross-reactivity of a desipramine-elicited monoclonal antibody with other tricyclic antidepressants. An unexpected finding to emerge from this immunochemical study is the demonstration that a single affinity constant suffices to describe the interaction of desipramine with a polyclonal antibody elicited by this univalent antigen. PMID- 1922114 TI - Cellular aspects of pattern formation: the problem of assembly. PMID- 1922115 TI - [Pre- and perinatal infections with sexually transmissible microorganisms]. AB - The sexually transmissible pathogenic microorganisms, which are also capable of initiating pre- or perinatal infections, include Neisseria gonorrhoeae, Treponema pallidum, Chlamydia trachomatis serovars D through K, group B streptococci, urogenital mycoplasmas, herpes simplex viruses types I and II, cytomegalovirus, hepatitis B virus, human immunodeficiency viruses, human papillomaviruses, Candida spp. and Trichomonas vaginalis. With special emphasis on paediatric and neonatological aspects, brief discussions of the following topics are presented: the epidemiology of these agents, the diseases they can induce in pregnancy, the mode of infection of and the diseases in the fetus and neonate, the preventive measures, the diagnosis and therapy. PMID- 1922116 TI - [HIV infection. Immunopathology and pathogenesis]. AB - More recent knowledge on pathogenesis and immunopathology of HIV-infection permit more hope for progress in prevention and treatment. The important steps of viral replication and persistence are restated. The considerable magnitude of HIV plasma viremia during all disease stages implies relevant conclusions concerning diagnosis, therapy and virulence. Variable pathogenesis of HIV-infection is based on viral features, cofactors and immunopathological events. PMID- 1922117 TI - [13 parameters of coagulation and fibrinolysis--univariate pediatric normal values of hemostasis]. AB - In order to establish age related univariate nonparametric tolerance regions in 74 healthy children and adolescents (age 2-18 years) undergoing elective surgery the following haemostatic parameters have been investigated: platelet count, von Willebrand factor, factor VIIIC, ristocetin-cofactor, antithrombin III, protein C fibrinogen, plasminogen, alpha-2-antiplasmin, C1-inactivator, alpha-1 antitrypsin, alpha-1-antichymotrypsin and alpha-macroglobulin. Compared to adult normal values medians of von Willebrand factor and protein C were lowered, alpha 2-antiplasmin, C1-inactivator and alpha-2-macroglobulin were elevated, whereas the medians of alpha-1-antitrypsin and alpha-1-antichymotrypsin reached the lower adult borderline. The other investigated parameters showed no difference to those of adults. PMID- 1922118 TI - [Cystic fibrosis and pregnancy. Current results of a study (1980-1990)]. AB - This study is a recent collection of data on 19 women with cystic fibrosis who became pregnant between 1980 and 1990. The following data have been recorded:- age at diagnosis, progress of disease prior and during pregnancy, and during confinement. Satisfactory clinical score values and the fact that the mean age at diagnosis was 10.5 years indicated a less serious nature of the disease in the group studied. Pregnancy was complicated by pulmonary exacerbations and by poor weight gain in two thirds of cases. No maternal deaths during pregnancy and delivery were recorded. Abortions were induced in two pregnancies. More than one third of newborns were premature. It is noteworthy that of the 22 infants 16 were male. All of the children had negative sweat chloride tests. Eleven women could breast feed successfully. In twelve cases the mother's state of health deteriorated after pregnancy, and did not return to that before gravidity. PMID- 1922119 TI - [The developmental prognosis of children with 5-day seizures]. AB - We report on the course of development of 23 children with fifth-day fits during the years 1980 to 1985. The age of examination was 4.6 years on average. 21 cases had a neurodevelopmental examination including an EEG-recording. In two further cases developmental data could be obtained by an interview by phone. We obtained the following results: 2 children developed epilepsy. Normal development was seen in 9 children. The developmental abnormalities became manifest in children older than 30 months. There is no homogeneous profile of abnormalities of development. Therefore we suggest to perform differentiated and multidisciplinary investigations in the follow up of children with fifth day fits. Similar to the observations in Australia and Italy, we could not see any more case of fifth-day fit since 1985. PMID- 1922120 TI - [LFA-1 defect: a rare granulocyte function disorders as a cause of therapy resistant omphalitis in newborn infants]. AB - A newborn infant suffered from severe omphalitis resistant to antibiotic therapy. The combination of the symptoms: delayed separation of the umbilical cord, omphalitis, impairment of wound-healing and extreme leukocytosis led to the diagnosis of LFA-1 (leukocyte function antigen)-deficiency, which was confirmed by monoclonal antibodies. The pathophysiology of this disorder is described shortly. PMID- 1922121 TI - [Single incisor syndrome and growth hormone deficiency]. AB - The syndrome of single incisor belongs to the group of midline malformations and is characterized by a single incisor in the patient's maxilla. A growth hormone deficiency (GHD) can be associated. We report about two of our patients with this syndrome. A GHD was diagnosed at the age of 11.0 and 7.6 years, respectively, although a single incisor had already been present during their first dentition. The first patient was treated with HGH to a chronological age of 18.6 years (final height 168 cm), the second patient is still on therapy. The growth of children with craniofacial dysmorphic features must be controlled closely in order to diagnose a GHD in time. PMID- 1922122 TI - [Borrelia infections from a dermatological viewpoint]. AB - Erythema migrans (EM), Borrelia lymphocytoma (BL) and acrodermatitis chronica atrophicans (ACA) are the established dermatological manifestations of borrelia infection, a complex multiorganic disease. Analogous to syphilis Borrelia infection can be classified by three stages, at which stage I (localized infection) and II (disseminated infection) are manifestations of early infection and stage III (persistent infection) a symptom of late infection. At all stages skin manifestations can be present, the above mentioned as stage-marker as well as other non-specific polymorphous skin lesions which sometimes appear at stage II. Because of its frequent (60-80%) occurrence in all borrelia infections EM has a pathognomonic importance for borrelia infection. In diagnosis serology is currently the only practical laboratory aid. False negative and false positive results must be considered. Treatment of choice is ceftriaxone, penicillin G (or amoxycillin) or tetracycline. Prophylactic antibiotic therapy for tick bites is not recommended. Congenital borrelia infections seem to be unusual, but it is likely that they can occur and cause different adverse fetal outcome or abortion. PMID- 1922123 TI - Modeling the functional organization of the basal ganglia. A parallel distributed processing approach. AB - Despite recent advances in the understanding of the pathophysiology of movement disorders, little is known about the precise function the basal ganglia play in the control of movement. We review an approach to studying the function of neural systems that is based on the use of a class of computer models known as parallel distributed processors (PDPs) and indicate its potential range of applications to the study of movement disorders. PDPs can be used to construct computational devices that take into account the anatomical and pharmacological properties of real neural systems. They can also provide computational-level insights that can lead to novel hypotheses concerning brain function. We discuss both these approaches and outline a scheme of the functional organization of the basal ganglia, which predicts some of the pathophysiological mechanisms that mediate movement disorders and which can be formally modeled on a computer. PMID- 1922124 TI - A clinical and genetic study of familial Parkinson's disease. AB - The clinical features of familial Parkinson's disease (PD) were investigated by examining the families of 20 British probands who were selected on the basis of having clinically typical PD and at least one affected relative. Forty-nine secondary cases were identified. These subjects were clinically indistinguishable from sporadic cases of idiopathic PD. If it is assumed that familial PD has a genetic basis, pedigree and segregation analysis suggested autosomal dominant inheritance of a gene or genes with reduced penetrance as the most likely explanation. The data did not support the possibilities of either mitochondrial or polygenic inheritance, although the latter cannot be excluded. The role of genetic factors in sporadic cases of PD remains unclear. PMID- 1922125 TI - Absorption of apomorphine by various routes in parkinsonism. AB - We wanted to determine the absorption and clinical effect of sublingual (SL) and transdermal apomorphine in parkinsonism. Patients received single SL apomorphine doses (N = 7) and the absorption was compared with parenteral (N = 5) and oral (N = 4) doses. One patient received a transdermal dose of apomorphine. The relative bioavailability of SL apomorphine ranged from 10 to 22% of a parenteral apomorphine dose. Oral apomorphine was less than 4% bioavailable, and the transdermal dose did not produce detectable plasma levels. Three patients with motor fluctuations responded to SL apomorphine, with a latency to effect of 20-40 min and a duration of effect of 15-100 min. One patient used SL apomorphine as an adjunct with levodopa, and during 1 month reported a large decrease in "off" periods. We conclude that apomorphine is effectively absorbed by the sublingual route. PMID- 1922126 TI - Cortical activity preceding self-initiated and externally triggered voluntary movement. AB - The cortical electromyogram (EMG) activity, preceding voluntary movements, was recorded in 12 normal subjects in two different situations: first, when movements were self-induced by the subjects by their own will; and second, in response to threshold electrical stimulation of the index finger, a brief flash of a light emitting diode (LED), and a click. Four types of movements were studied: (a) fast extension of the right wrist, (b) fast supination of the left wrist, (c) either movement depending on the subject's own decision or on which index finger was stimulated, and (d) fast sequential right and left wrist extension. In all subjects, self-initiated movements were preceded by a typical Bereitschaftspotential (BP) starting 1,290 +/- 208 ms before the EMG discharge. When the same movements were triggered by an external clue, there was no BP. The BP was present, although with a shorter duration, when subjects were asked to wait for a brief period after index finger stimulation, before extending the right wrist. From these results, we conclude that the BP is closely associated with the timing of internally generated movements, and that different cortical areas are probably involved in the generation of self-induced and externally referenced movements in humans. PMID- 1922127 TI - Prior history of head trauma in Parkinson's disease. AB - The purpose of this study was to evaluate the relationship between head trauma and Parkinson's disease (PD). A questionnaire was completed by 97 PD patients (mean age 68.6 years, duration of disease 6.4 years) and 64 spouses acting as controls (mean age 63 years). Thirty-one PD patients reported head trauma before onset of PD (mean 32.3 years earlier), whereas 11 controls reported head injury before completing the survey (mean 26 years earlier) (p less than 0.05). Twenty PD patients and five controls reported head injury associated with alteration or loss of consciousness (p less than 0.05). Injury occurred a mean of 37.7 years before onset of PD and 37.2 years before survey completion in the two groups, respectively. In both of these comparisons we adjusted the frequencies to eliminate sex differences between groups. Comparison of new frequencies showed differences that were not significant. However, a trend toward significance was observed when examining head trauma with alteration of consciousness. Other investigators have reported similar results indicating that previous head trauma may be a risk factor in the etiology of PD. However, recall bias might have an effect on the outcome of these studies and this is discussed. The relationship between head trauma and PD is still tenuous. PMID- 1922128 TI - Tremor and idiopathic dystonia. AB - The clinical and electromyographic characteristics of tremor were studied in 45 patients presenting with various forms of idiopathic dystonia. Dystonic tremor was shown to be postural, localized, and irregular in amplitude and periodicity, absent during muscle relaxation, exacerbated by smooth muscle contraction, and associated frequently with myoclonus. Although it resembles essential tremor, dystonic tremor seems to be a distinct entity: it is more irregular with a broader range of frequencies; it is asymmetric and remains localized; myoclonus is sometimes associated. This type of tremor is most often seen in the presence of dystonia, but may be observed without evident dystonic symptoms. PMID- 1922129 TI - Hereditary essential myoclonus in a large Norwegian family. AB - We examined 56 members of a large Norwegian family with hereditary essential myoclonus, affecting mainly the neck and upper parts of the body, and inherited in an autosomal-dominant pattern. We observed definite myoclonus in nine individuals, probable myoclonus in one, and possible myoclonus in one. There were two other living members who had a history compatible with myoclonus but who had developed a permanent remission, so we did not observe the movements, and two who had involuntary movements only with stress. Writing usually increased the myoclonus in the neck and trunk, but did not produce myoclonus in the arm used for writing. Having a conversation with an individual who was aware of being watched would also usually increase the myoclonus. Alcohol ameliorated the myoclonus in many, but not all, affected members. Activities such as walking and concentrating during reading would usually reduce the myoclonus. Three living members with definite myoclonus also had features of mild focal dystonia, either spasmodic torticollis or blepharospasm, indicating that focal dystonia may exist as part of the clinical spectrum in hereditary essential myoclonus. In addition to examining the members of the family, we videotaped them and obtained blood samples for molecular genetic analysis. PMID- 1922130 TI - Dystonic tics in patients with Tourette's syndrome. AB - Dystonic tics, in contrast to clonic tics, are relatively slow and temporarily sustained twisting, pulling, or squeezing movements producing briefly maintained abnormal postures. Because dystonic tics often present diagnostic difficulties, we studied these motor tics in 156 patients with Tourette's syndrome (TS). In addition to clonic motor and vocal/phonic tics, seen in all patients, 89 (57%) of them exhibited one or more dystonic tics. The most common dystonic tics were oculogyric deviations (43 patients), blepharospasm (23), and dystonic neck movements (11). Blinking (110) and facial twitching (86) were the most common clonic tics. Except for possibly a greater familial occurrence, a higher frequency of previous head trauma, and associated attention deficit disorder, the group of patients with dystonic tics did not significantly differ in any of the major clinical variables from those TS patients without dystonic tics. We conclude that dystonic tics are typical motor manifestations of TS and that patients with these motor tics are not different from those with more typical clonic tics. PMID- 1922131 TI - Parkinsonism and extraocular motor abnormalities with unusual neuropathological findings. AB - Parkinsonian patients with ocular motility abnormalities are usually considered to have progressive supranuclear palsy. However, a number of other conditions have been noted to have the combination of parkinsonism and ocular problems. We report a case of rigid akinetic parkinsonism, oculomotor palsy, and eyelid apraxia with postmortem examination. Our findings are unusual in that there was marked gliosis of the substantia nigra with a large amount of free extracellular neuromelanin despite a 3-year clinical course. Only rare hyaline inclusion bodies and no neurofibrillary tangles were seen in the brainstem. Excessive calcification of the vessels of the globus pallidus were also noted. This case represents another example of the diversity of conditions producing parkinsonism with extraocular motor abnormalities. PMID- 1922132 TI - Combined resting-postural tremor of the head with a changing axis. AB - When essential tremor involves the head, it produces a rhythmic, periodic movement with a certain fixed frequency and a variable amplitude. The axis of the tremor has been described as either horizontal (no-no) or vertical (yes-yes) and is present when the head is in an action or postural position. Seven patients who differ in symptoms are described; one subgroup exhibited a combined resting postural tremor of the head, sometimes with a changing axis; three patients had only postural head tremor with a changing axis. PMID- 1922133 TI - Dystonia and reflex sympathetic dystrophy induced by ergotamine. AB - A 59-year-old man developed dystonia and reflex sympathetic dystrophy after receiving high doses of ergotamine for migraine treatment. Ischemia is suggested as the precipitating factor. PMID- 1922134 TI - Electroconvulsive therapy in untreated Parkinson's disease. PMID- 1922135 TI - Orthostatic tremor. PMID- 1922136 TI - Hidden skills: a dynamic systems analysis of treadmill stepping during the first year. AB - When prelocomotor infants are supported on a motorized treadmill, they perform well-coordinated, alternating stepping movements that are kinematically similar to upright bipedal locomotion. This behavior appeared to be a component of independent walking that could not be recognized without the facilitating context of the treadmill. To understand the ontogenetic origins of treadmill stepping and its relation to later locomotion, we conducted a longitudinal study using an experimental strategy explicitly derived from dynamic systems theory. Dynamic systems theory postulates that new forms in behavior emerge from the cooperative interactions of multiple components within a task context. This approach focuses on the transitions, often nonlinear, where one preferred mode of behavior is replaced by a new form. Specific predictions about these transitions help uncover the processes by which development proceeds. Chapters II, III, and IV introduce dynamic principles of pattern formation and their application to development. In our application of these principles, we tested nine normal infants twice each month beginning from month 1 in a task where the treadmill speed was gradually scaled up and in an additional condition where each leg was driven by the treadmill at a different speed. Kinematic variables were derived from computerized movement analysis equipment and videotaped records. We also collected a number of anthropometric measurements, Bayley motor scores, and a behavioral mood scale for each month. Several infants stepped on the treadmill in their first month, but in all infants performance showed a rapidly rising slope from month 3 to month 6. Infants also showed corresponding improvement in adjustments to speed and relative coordination between the legs. In dynamic terminology, we found evidence that alternating stepping on the treadmill became an increasingly stable attractor during the middle months of the first year. Dynamic predictions that transitions would be characterized by increased variability and sensitivity to perturbation were borne out. Identifying the transitions enabled us to suggest a control parameter or variable moving the system into the stable response to the treadmill. This appeared to be the waning of flexor dominance in the legs during posture and movement that allowed the leg to be stretched back on the treadmill and so elicited the bilaterally alternating response. Further studies are needed to test this hypothesis. This dynamic analysis confirmed earlier suggestions that skill in general, and locomotion in particular, develops from the confluence of many participating elements and showed how emergent forms may result from changes in nonspecific components. A dynamic approach may be useful for understanding ontogenetic processes in other domains as well. PMID- 1922137 TI - What indication is common to different genotoxicity data bases? AB - This paper studies the relationships among 4 in vitro assays: Salmonella mutation (STY), mouse lymphoma L5178Y cell mutation (MLY), chromosomal aberrations in CHO cells (CHA), and sister-chromatid exchanges in CHO cells (SCE), in 3 different data bases: U.S. National Toxicology Program (NTP), International Program for the Evaluation of Short-Term Tests for Carcinogens (IPESTTC), and International Program on Chemical Safety (IPCS). The analysis is performed by modeling each data base with factor analysis. With this tool, it has been possible to separate the different elements (or components) which play a role in each data base. It has also been possible to demonstrate that--together with some specificities of the data bases--there is a common effect which is independent of the data bases, and which typically represents the 'true' relationships among the assays. This element explains 69% of the information contained in NTP, 50% of that of IPESTTC, and 30% of that of IPCS. This common evidence indicates that the responses of STY and CHA to the 'universe' of chemicals are relatively similar, although STY is a bacterial mutation system and CHA is a mammalian cell test for chromosomal damage. The other similarity apparent from this analysis is the one between MLY (mutation in mouse cells) and SCE (cytogenetic evidence in hamster cells). The implication of this result is 2-fold. On the one hand, it is extremely reassuring that the 3 most important comparative studies agree and show common evidence, and this can be recognized rationally. On the other hand, this evidence implies that the scientists involved in mutagenicity research must face the task of exploring and explaining such relationships. PMID- 1922138 TI - Treatment of mice with a herbal preparation (Liv. 52) reduces the frequency of radiation-induced chromosome damage in bone marrow. AB - Induction of chromosomal aberrations was studied from 1/4 to 14 days post irradiation in the bone marrow of mice treated or not with Liv. 52, a herbal preparation, prior to 4.5 Gy exposure. The frequency of chromatid and chromosomal aberrations started increasing at day 1/4 in the irradiation and Liv. 52 + irradiated groups. The highest frequency of aberrations was recorded at day 1/2 post exposure which declined after day 1 in both groups. The frequency of both types of aberrations was significantly lower in the Liv. 52 + irradiated group than in the irradiated group. PMID- 1922139 TI - Evaluating the relationship of metabolic activation system concentrations and chemical dose concentrations for the Salmonella spiral and plate assays. AB - A factorial experimental design was used within this study to evaluate the influence of multiple metabolic activation system concentrations on the dose response exhibited by promutagens (indirect-acting mutagens) in the Salmonella spiral and plate assays. The mutagenic activity of the three compounds used spanned three orders of magnitude. The mutagenic activity of the compounds ranged from 10 to 100 revertants/micrograms for acetylaminofluorene (2AAF) to more than 1000 revertants/micrograms for 2-aminoanthracene (2AA). Benzo [a] pyrene (BaP) activity was within an intermediate range (100-1000 revertants/micrograms). During a single experiment, a mutagen was tested in TA100 at 13 doses plus a negative control dose. Each dose was tested at 10 S9 concentrations. The S9 concentrations ranged from 0.1 mg protein/plate to 4 mg protein/plate in the standard plate assay and from 0.25 to 4.90 mg-equivalents in the spiral assay. The spiral Salmonella assay, an automated version of the standard assay, generates dose-response data from a concentration gradient on a single agar plate, thereby providing a straightforward approach to this type of study. This study demonstrates not only that even small differences in S9 concentrations can affect the measurement of mutagenic potency but that S9/compound interactions cannot be generalized through the use of interaction studies. This study also shows that spiral assay data and plate assay data for promutagens cannot be compared directly unless the S9 concentrations for all chemical doses are also comparable. PMID- 1922140 TI - Assessing the use of known mutagens to calibrate the Salmonella typhimurium mutagenicity assay: I. Without exogenous activation. AB - There has been an increasing need in genetic toxicology to progress from strictly qualitative tests to more quantitative tests. This, in turn, has increased the need to develop better quality assurance and comparative bioassay methods. In this paper, two laboratories tested 10 Salmonella mutagens in order to determine the usefulness of selected chemicals as potential reference materials to calibrate the Salmonella assay. If variance within a bioassay is sufficiently low and the rankings of the compounds are of acceptable consistency, the chemicals later could be evaluated for use as standard control compounds, as audit materials, and as standard reference materials for comparative bioassay efforts. The results demonstrated that the chosen chemicals (with the possible exception of dimethylcarbamylchloride) provide such consistent results in the Salmonella mutagenicity bioassay that they can be used for semi-quantitative calibration and as possible bioassay controls, special audit chemicals, and potentially as reference standards in comparative bioassay efforts. Reference standards, whether used as audit materials or in comparative bioassays, must be used concurrently with the test substances of interest; used without bias; used in a standardized, highly controlled bioassay; and be tested across an appropriate dose range. The study also shows that when these compounds are used as reference standards much care must be given to the number and spacing of doses if highly reproducible slope values are to be generated. We recommend use of a pilot test to establish a dose range for definitive tests and the placement of doses for the definitive tests within the first half of the linear dose-response curve. For appropriate comparisons, one should replicate the tests using the defined dose range and analyze the results in a non-biased statistical manner. PMID- 1922141 TI - Assessing the use of known mutagens to calibrate the Salmonella typhimurium mutagenicity assay: II. With exogenous activation. AB - In order to determine the usefulness of selected chemicals as potential reference materials for calibrating the Salmonella assay, two laboratories tested a series of Salmonella mutagens that require exogenous activation. When the variance for individual substances within a bioassay is sufficiently low and the rankings of those substances are of acceptable consistency, they can later be evaluated for use as standard control compounds, as audit materials, and as standard reference materials for comparative bioassay efforts. The purpose of this project, therefore, was to evaluate the variability in the mutagenic response of potential reference chemicals that require exogenous metabolic activation in the standard plate-incorporation Salmonella mutagenicity assay, and to develop ranking criteria for mutagenic activity based on these data. Ten indirect-acting mutagens were tested in two laboratories using Salmonella typhimurium TA100 and an Aroclor induced rat liver S9. Each laboratory conducted four definitive testing rounds. A different batch of S9 was utilized for every two rounds. Of the 10 chemicals tested only 2-anthramine had a mean slope value greater than 1000 revertants/micrograms. Three chemicals had slope values between 1000 and 100; and five chemicals had slope values between 100 and 10. The remaining compound, 9,10 dimethyl-1,2-benz[a]anthracene, could not be placed into a single category because it had slope values on either side of 100 revertants per mg. Coefficients of variance were low (i.e., below 25% in most cases). The low variability achieved in this study may be accounted for by two parameters of the study. First, based on Claxton et al. (1991a) and the S9 optimization for three compounds, the amount of S9 was calibrated to a set amount of protein per plate (1.1 mg/plate). Secondly, the 10 test doses were placed in the initial, linear, nontoxic portion of the dose-response curves. The use of ten closely spaced, nontoxic doses allowed for a more accurate estimate of the slope. PMID- 1922142 TI - A cytogenetic approach for detecting the selective toxicity of drugs in avian embryonic B and T lymphocytes. AB - The developing immune system of late stage embryos and neonates may be particularly susceptible to the toxicity of drugs and environmental contaminants due to high rates of cell proliferation and ongoing processes of differentiation. We have developed a cytogenetic assay to study the mechanisms of the selective targeting of cyclophosphamide (CP) to B lymphocytes compared to T lymphocytes in chicken embryos at days 18-19 of incubation. 5-Bromo-2'-deoxyuridine (BrdU; 3 mg/200 microliters PBS; two doses; 3-h interval) was pipetted onto the inner shell membrane in order to label DNA of replicating lymphoid cells. CP (1.25-40 mg/kg) was injected 1 h after the initial BrdU dose, and the embryos were exposed to colcemid (10 micrograms/100 microliters H2O) at hour 17. Three hours later, the bursa and thymus were removed, and the lymphocytes were swollen in hypotonic solution, fixed, and processed through a fluorescence-plus-Giemsa technique to differentiate sister chromatids. Based on reductions in mitotic indices, B cells were approximately 213 times more susceptible than T cells to the cytotoxicity of CP. Because the mitotic indices of B and T cells were comparable (21.3 +/- 3.7%, vs. 25.5 +/- 6.9%), the differential toxicity cannot be ascribed to greater numbers of B cells being in mitosis. CP induced a dose-related increase in the sister-chromatid exchange frequency in B cells of up to 10.4-fold above controls, representing one of the most sensitive vertebrate systems for detecting the genotoxicity of CP. The average generation time was slowed from 9.8 +/- 0.3 h in control B cells to 19.4 +/- 0.9 h in embryos exposed to 10 mg CP/kg. Furthermore, an analysis of control SCE data from 56 embryos indicated that there was a significant overdispersion of B cells exhibiting relatively high SCE frequencies compared to a Poisson distribution. Our data indicate that the chicken embryo in the late developmental stage is a good model for detecting the presence and selective toxicity of drugs and environmental toxins in differentiating B and T lymphocytes in vivo. PMID- 1922143 TI - Application of the neutral red assay (NR assay) to monolayer cultures of primary hepatocytes: rapid colorimetric viability determination for the unscheduled DNA synthesis test (UDS). AB - The neutral red (NR) absorption method was adapted for the determination of cell viability in the UDS assay with primary hepatocyte cultures of the rat. The NR method is rapid, easy to perform, and suitable for handling of large numbers of cultures simultaneously. It can be used for concentration range-finding pre experiments. In addition, it can easily be integrated into a UDS test protocol for documentation of toxic effects if supplementary cultures for each concentration are established. The time schedule required for the NR assay makes it possible for one person to process the hepatocytes for autoradiography and at the same time determine the toxicity. PMID- 1922144 TI - Inhibition of dinitropyrene mutagenicity in vitro and in vivo using Salmonella typhimurium and the intrasanguinous host-mediated assay. AB - Dinitropyrenes (DNP), present in polluted air, are potent direct-acting mutagens in Salmonella typhimurium TA98. This mutagenicity is markedly reduced in the presence of rat-liver S9 or microsomes. This has now been confirmed using mouse hepatic fractions. Since most in vitro test systems do not adequately simulate conditions encountered in the intact animal, we have investigated dinitropyrene mutagenicity to Salmonella in the host-mediated assay. 1,8-Dinitropyrene (1,8 DNP) given p.o. to BALB/c mice induced a weak mutagenic effect in S. typhimurium TA98 recovered from the liver 1 h after i.v. administration (optimum time). Over the entire dose range tested no toxicity to bacterial cells was detected. Mutation induction in vivo was dose-related with maximum response at 1 mg DNP/kg body weight. This optimum dose, however, was non-mutagenic to strains TA98/1,8 DNP6 (O-transacetylase-deficient) or TA98NR/1,8-DNP6 (nitroreductase- and O transacetylase-deficient). 1,3-Dinitropyrene and 1,6-dinitropyrene were weakly mutagenic to TA98 at doses similar to 1,8-DNP. Studies with [14C]1,8-DNP showed that 1 h after oral dosing (1 mg/kg), over 100 ng of 1,8-DNP equivalents were present in the liver (= 0.73% dose). However, only about 5.5 ng were present in the bacterial pellet, suggesting that hepatic components in vivo, as in vitro, bind to DNP, thus interfering with its interaction with Salmonella. PMID- 1922145 TI - Induction of micronuclei by X-radiation in human, mouse and rat peripheral blood lymphocytes. AB - We compared the radiosensitivity of human, rat and mouse peripheral blood lymphocytes (PBLs) by analyzing micronuclei (MN) in cytochalasin B-induced binucleated (BN) cells. For each species and dose 4-ml aliquots of whole blood were X-irradiated to obtain doses of 38, 75, 150 or 300 cGy. Controls were sham irradiated. After exposure to X-rays, mononuclear leukocytes were isolated using density gradients and cultured in RPMI 1640 medium containing phytohemagglutinin to stimulate mitogenesis. At 21 h cytochalasin B was added to produce BN PBLs, and all cultures were harvested at 52 h post-initiation using a cytocentrifuge. Significant dose-dependent increases in the percentage of micronucleated cells and the number of MN per BN cell were observed in all three species. The linear quadratic regression curves for the total percentage of micronucleated cells for the three species were similar; however, the curve for the mouse PBLs had a larger quadratic component than either of the curves for the rat or human PBLs. Although the correlation between the percentage of cells with MN and those with chromosome aberrations was high (r2 greater than 0.95), the mouse and rat PBLs were over twice as efficient as human PBLs in forming MN from presumed acentric fragments. These data indicate that the induction of MN in BN cells following ionizing radiation is similar in human, rat and mouse PBLs, but care must be taken in using the MN results to predict frequencies of cells with chromosomal aberrations. PMID- 1922146 TI - Use of the clonal assay for the measurement of frequencies of HPRT mutants in T lymphocytes from five control populations. AB - The clonal assay was used to measure frequencies of 6-thioguanine-resistant (HPRT) T-lymphocytes in 111 donors from the following 5 control populations: 55 adult healthy volunteers; 20 untreated cancer patients; 8 healthy hospital workers serving as controls for 9 hospital workers sterilizing equipment with ethylene oxide; 15 factory workers serving as controls for 15 workers occupationally exposed to high doses of ethylene oxide; 13 pretreatment samples from donors undergoing a diagnostic test with Technetium-99m for an analysis of heart function. With respect to mutant frequency (MF), cloning efficiency (CE) and age distribution, the first 4 populations were identical. The Technetium group had significantly higher MFs and lower CEs but this can be attributed to the higher mean age of this group. Using the total data base, we calculated the following relationships between MF, CE, age and smoking: (1) ln MF = 4.23-0.63 x ln CE indicating that a doubling of the CE has the effect of decreasing the MF by 37%, (2) ln MF = 0.71 + 0.03 x age meaning that the MF increases by 3% from one year to the next, (3) ln CE = 4.87-0.04 X age indicating that the CE decreases by 0.98% from one year to the next, (4) ln MF = 3.25-0.52 x ln CE + 0.02 X age being the equation quantifying the interrelationship between MF, CE and age, (5) ln MF = 3.32-0.56 x ln CE + 0.01 x age + 0.31 s (where s = 1 for smokers and s = 0 for nonsmokers). Using the latter equation, which allows for effects of CE and age on the MF, a statistically significant effect of smoking could be established. For any combination of CE and age smoking has the effect of increasing the MF by 36%. The above conclusions and calculations remain essentially the same when donors with cloning efficiencies lower than 10 or 20% are excluded from the data base. PMID- 1922147 TI - Cross-sensitivity of gamma-ray-sensitive hamster mutants to cross-linking agents. AB - A range of hamster cell mutants, which have been characterised as sensitive to ionising radiation, were examined for their cross-sensitivity to four DNA-DNA cross-linking agents and the protein-DNA cross-linking agent, camptothecin. The mutants represent 7 distinct complementation groups. Two complementation groups were identified as having a major sensitivity to cross-linking damage, more marked than their sensitivity to ionising radiation (irs1, irs1SF). These two mutants also show sensitivity to UV-irradiation. Two of the remaining complementation groups (xrs and XR-1) have a defect in rejoining DNA double strand breaks, and these exhibit sensitivity to 3 of the 4 DNA-DNA cross-linking agents. The results with these mutants suggest an involvement of double-strand break rejoining in the repair of certain cross-link damage. Two mutants were also notably sensitive to the topoisomerase I inhibiting anticancer drug, camptothecin. One of these mutants was sensitive to the DNA cross-linking agents examined (irs1SF), but the other was not at all sensitive to this class of drug (EM9). PMID- 1922148 TI - Does trans-lesion synthesis explain the UV-radiation resistance of DNA synthesis in C. elegans embryos? AB - Over 10-fold larger fluences were required to inhibit both DNA synthesis and cell division in wild-type C. elegans embryos as compared with other model systems or C. elegans rad mutants. In addition, unlike in other organisms, the molecular weight of daughter DNA strands was reduced only after large, superlethal fluences. The molecular weight of nascent DNA fragments exceeded the interdimer distance by up to 19-fold, indicating that C. elegans embryos can replicate through non-instructional lesions. This putative trans-lesion synthetic capability may explain the refractory nature of UV radiation on embryonic DNA synthesis and nuclear division in C. elegans. PMID- 1922149 TI - The origin of O6-methylguanine-DNA methyltransferase in Chinese hamster ovary cells transfected with human DNA. AB - Transfection of Chinese hamster ovary (CHO) cells with human DNA has been shown in several laboratories to produce clones which stably express the DNA-repair protein, O6-methylguanine-DNA methyltransferase (MGMT), that is lacking in the parent cell lines (Mex- phenotype). We have investigated the genetic origin of the MGMT in a number of such MGMT-positive (Mex+) clones by using human MGMT cDNA and anti-human MGMT antibodies as probes. None of the five independently isolated Mex+ lines has human MGMT gene sequences. Immunoblot analysis confirmed the absence of the human protein in the extracts of these cells. The MGMT mRNA in the lines that express low levels of MGMT (0.6-1.4 x 10(4) molecules/cell) is of the same size (1.1 kb) as that present in hamster liver. One cell line, GC-1, with a much higher level of MGMT (4 x 10(4) molecules/cell) has two MGMT mRNAs, a major species of 1.3 kb and a minor species of 1.8 kb. It has also two MGMT polypeptides (32 and 28 kDa), both of which are larger than the 25 kDa MGMT present in hamster liver and other Mex+ transfectants. These results indicate that the MGMT in all Mex+ CHO cell clones is encoded by the endogenous gene. While spontaneous activation of the MGMT gene cannot be ruled out in the Mex+ cell clones, the intervention of human DNA sequences may be responsible for activation of the endogenous gene in the GC-1 line. PMID- 1922150 TI - The genetic defect in the Chinese hamster ovary cell mutant UV61 permits moderate selective repair of cyclobutane pyrimidine dimers in an expressed gene. AB - We examined removal of cyclobutane pyrimidine dimers (CPDs) from the dihydrofolate reductase (DHFR) gene in ultraviolet-irradiated Chinese hamster ovary (CHO) UV61 and UV5 cells. The sensitivity of UV61 cells to UV-irradiation is intermediate between that of the parental CHO cells and that of mutants such as UV5 that are highly defective in excision repair. UV61 cells have been characterized as having normal repair of pyrimidine(6-4)pyrimidone photoproducts (6-4 PPs) but no detectable removal of CPDs from the genome overall. We find that the extent of removal of CPDs from the DHFR gene in UV61 cells is intermediate between that of the parental CHO cells and that of the UV5 mutant, and the observed repair appears to be confined to the transcribed strand. We detected no removal of CPDs from the DHFR gene in UV5 cells. Our findings in UV61 cells demonstrate a correlation between survival after UV-irradiation and CPD repair in an expressed gene in a cell line with moderate UV-sensitivity and yet no apparent removal of CPDs from the genome as a whole. We have thus demonstrated that overall repair measurements can be misleading. Our results have implications for the determination of the relative biological importance of the CPD and the 6-4 PP, and they further support the hypothesis that removal of CPDs from transcriptionally active DNA is crucial for UV-resistance. PMID- 1922151 TI - Oxidative stress effects on conjugational recombination and mutation in catalase deficient Escherichia coli. AB - The objective of the present investigation was to determine the effects on genetic recombination and mutation in Escherichia coli of either endogenous increases in oxygen radicals resulting from catalase deficiencies, or exogenous increases resulting from H2O2 treatment. Using the classical paradigm of Escherichia coli bacterial conjugation, strains deficient in the production of hydroperoxidase I (HPI) and/or hydroperoxidase II (HPII) were used as recipients in Hfr x F- matings. 'Background' recombination rates, measured by the rate of appearance of threonine prototrophs, was similar to wild-type levels in the HPI deficient (katG) strain, but were significantly decreased in HPII- (katE) mutants. The addition of relatively nontoxic H2O2 concentrations (0.25 mmoles dm 3) to the mating mixtures stimulated recombination rates in wild-type and katE strains, but decreased rates in katG and katEkatG strains. A 0.5 mmoles dm-3 concentration of H2O2 inhibited recombination rates in all strains. In order to gauge the level of recA-dependent 'SOS' processes occurring under the experimental conditions, 'background' mutation rates were determined in both fluctuation and forward mutation (thyA) assays. Mutation rates in aerobically grown cultures were increased up to 2.2-fold in katG and katEkatG strains. Treatment with relatively nontoxic H2O2 concentrations elevated the thyA mutagenesis up to 8-fold in catalase-deficient cultures. Furthermore, these studies along with data presented elsewhere show that the SOS phenotype of katEkatG is more resistant than that of katG strains. These studies clearly show that cellular oxidative stress occurring from catalase deficiency interferes with normal DNA metabolism. PMID- 1922152 TI - Xeroderma pigmentosum complementation group H falls into complementation group D. PMID- 1922153 TI - Genotoxicity testing of extracts of a Swedish moist oral snuff. AB - The present study was designed to investigate the potential genotoxicity of aqueous and methylene chloride extracts of Swedish moist oral snuff. The test systems were selected to provide optimal data for the prediction of carcinogenicity in rodents and included assays for the induction of mutation in bacteria, sister-chromatid exchanges (SCE) in human lymphocytes, of chromosome aberrations and gene mutations in V79 Chinese hamster cells and of micronuclei in mouse bone marrow cells. In addition, the methylene chloride extract was tested for the induction of sex-linked recessive lethal mutations in Drosophila melanogaster. The aqueous extract of 'Snus' induced SCE in human lymphocytes and chromosome aberrations in V79 cells, the latter effect being observed both with and without metabolic activation. No induction of point mutations was detected with the Ames test or in V79 cells and the micronucleus test in mice was negative. It was demonstrated that the induction of chromosome aberrations without metabolic activation may be due to a high salt concentration, indicating that the clastogenic agent(s) in this extract required metabolic activation. The methylene chloride extract showed genotoxicity in the Ames test, the SCE test and the chromosome aberration test, whereas no induction of gene mutations in V79 cells was observed. Once again, the results suggested that metabolism is required for genotoxicity. The methylene chloride extract did not cause induction of micronuclei in mice or of sex-linked recessive lethal mutations in Drosophila melanogaster. These combined data on genotoxicity were analyzed using various models for the prediction of carcinogenicity. In a sequential testing model, the probabilities that the aqueous and methylene chloride extracts of 'Snus' are carcinogenic due to a genotoxic mechanism were both predicted to be low. Using carcinogenicity prediction by battery selection (CPBS), the probabilities of the methylene chloride and aqueous extracts being correctly identified as non carcinogens are 71 and 77%, respectively. Up to date, the CPBS approach has been validated primarily for individual compounds, so some caution should at present be exercised in interpreting the results using this method. Based on these results, the carcinogenic potential of Swedish 'Snus' should be considered to be low, a conclusion in agreement with the low incidence of oral cancer in Sweden compared to other countries. PMID- 1922154 TI - 1,3-Butadiene and its epoxides induce sister-chromatid exchanges in human lymphocytes in vitro. AB - Sister-chromatid exchanges (SCEs) were induced in human lymphocytes by 1,3 butadiene and its epoxides 3,4-epoxy-1-butene and 1,2:3,4-diepoxybutane. After a pulse treatment of 2 h, 1,3-butadiene produced a weak but reproducible increase in SCEs both with and without S9 mix. The response was similar in cultures of whole blood and of isolated lymphocytes. The 2 epoxide metabolites of butadiene, studied in whole-blood lymphocyte cultures without exogenous metabolic activation, were highly active SCE inducers. The lowest effective concentrations of butadiene, monoepoxybutene, and diepoxybutane were 2000 microM, 25 microM and 0.5 microM, respectively. A slight but dose-dependent increase in SCEs was also observed without an exogenous metabolic system after a 48-h treatment with 1,3 butadiene. Already the lowest concentration tested (500 microM) was effective. Again, the response was similar in cultures of whole blood and isolated lymphocytes, suggesting that the lymphocytes are capable of metabolically activating 1,3-butadiene. PMID- 1922155 TI - Mutation of potassium permanganate- and hydrogen peroxide-treated plasmid pZ189 replicating in CV-1 monkey kidney cells. AB - We examined the effect of the oxidation of plasmid pZ189 by KMnO4, which does not produce free radicals, and H2O2/Fe(2+)-diethylenetriaminepentaacetic acid (DTPA), which does, on the mutation frequency of pZ189 transfected into monkey kidney CV 1 cells. Treatment with 1.5 mM KMnO4 increased the content of certain modified bases, principally Thy and Cyt modified at C-5 and C-6, by up to 300-fold, as measured by GC/MS; however, the mutation frequency increased only 5-fold above background. 1.0 mM H2O2/0.1 mM Fe(2+)-DTPA treatment, which increased the mutation frequency 10-fold above background, increased the content of certain modified bases by up to 4-fold. Sequence analysis revealed both deletions and point mutations, with a predominance of C-G substitutions, among H2O2/Fe(2+)-DTPA associated mutations. These data suggest that KMnO4-modified DNA is only weakly mutagenic in DNA replicating in mammalian nuclei, despite substantial production of Thy glycol and other base modifications, whereas H2O2/Fe(2+)-DTPA-modified DNA is more mutagenic. H2O2/Fe(2+)-DTPA generated mutations occur predominantly at C G base pairs. PMID- 1922156 TI - Mutagenicity of various chemicals including nickel and cobalt compounds in cultured mouse FM3A cells. AB - Employing a suspension culture of FM3A cells, we examined the cytotoxic and mutagenic effects of various chemical compounds. Mutagenicity of various types of mutagens (MNNG, ENNG, sterigmatocystin, mitomycin C, Trp-P-1, and X-rays) was sensitively detected by this assay. Mutagenicity of Trp-P-2 was detected in the presence of an activating enzyme system. Nickel(II) and cobalt(II) compounds (NiCl2, Ni(CH3COO)2, nickel complex [(C2H5)4N]2 [NiCl4], CoCl2, and a cobalt complex [(C2H5)4N]2-[CoCl4]) were cytotoxic to FM3A cells at concentrations of over 1 X 10(-4) M, and produced 2-6-fold increases of the control in the average number of 6-thioguanine-resistant (6TGr) colonies over a very narrow concentration range of 2-4 X 10(-4) M. Comparison of the mutagenicity of various chemical compounds suggested that some of the nickel(II) and cobalt(II) compounds were very weak mutagens. PMID- 1922157 TI - Biological monitoring of bidi rollers with respect to genotoxic hazards of occupational tobacco exposure. AB - Smokeless tobacco habits are associated with a high incidence of oropharyngeal cancer in India. Hence, the biological effects of occupational exposure to smokeless tobacco used for making bidis (the Indian version of cigarettes) were studied in 2 groups of bidi rollers designated BR-K and BR-S and in control subjects with no tobacco habits. Specific tobacco exposure and the electrophilic burden were determined by estimating urinary cotinine and thioethers respectively. Urine mutagenicity was tested with the Ames assay using Salmonella typhimurium strains TA98 and TA100. While cotinine was not detected in control samples, the mean cotinine levels (mmole/mole creatinine) in the BR-K and BR-S groups were 0.79 +/- 0.30 and 0.09 +/- 0.03 respectively. Urinary thioether excretion (mmole/mole creatinine) was significantly elevated in the BR-S group 4.59 +/- 0.52; p less than 0.001) but it was lower in the BR-K group (0.54 +/- 0.08; p less than 0.001) compared to the control (1.83 +/- 0.34). Furthermore, beta-glucuronidase-treated samples from both groups of bidi rollers exhibited increased mutagenicity to TA98 compared to the control group; in addition, BR-S samples exhibited direct mutagenicity to TA98. The results show that occupational tobacco exposure modulates the glutathione conjugation pathway and increases the mutagenic burden of bidi rollers. PMID- 1922158 TI - Mutagenicity of the coccidiostat diaveridine in the Salmonella/mammalian microsome assay. AB - The coccidiostat diaveridine was tested for mutagenicity in the Salmonella/microsome assay with tester strains TA100 and TA98. This compound was not mutagenic in either tester strain in the presence and absence of rat S9 mix, but was found to be mutagenic in strain TA100 after metabolic activation with hamster S9 mix. PMID- 1922159 TI - Dichloroacetonitrile, a by-product of water chlorination, induces aneuploidy in Drosophila. AB - Nitriles have been shown to be potent inducers of aneuploidy in yeast and Drosophila test systems. Haloacetonitriles are by-products of water chlorination that have been shown to be mutagenic and carcinogenic following topical application. In this report we show that dichloroacetonitrile, but not dibromoacetonitrile, is an effective inducer of aneuploidy in oocytes of Drosophila melanogaster. Following inhalation exposure of ZESTE adult females, dichloroacetonitrile (8.6 ppm) induced highly significant increments in the frequencies of sex chromosome loss and gain. Sodium cyanide was also found to be a highly effective inducer of germline aneuploidy, suggesting that cyanide toxicity may contribute to potency of nitriles as inducers of aneuploidy. PMID- 1922160 TI - Mutagenicity of processed bidi tobacco: possible relevance to bidi industry workers. AB - The genotoxic potential of bidi tobacco was evaluated by mutagenicity testing of aqueous, aqueous: ethanolic, ethanolic and chloroform extracts of processed tobacco used in the manufacture of 'bidis', indigenous forms of cigarettes smoked in India. The Salmonella/mammalian microsome test (Ames assay) was used to detect mutagenicity in tester strains TA98, TA100 and TA102. The extracts were tested in the absence and presence of metabolic activation using liver S9 from rat and hamster, and following in vitro nitrosation with sodium nitrite at acidic pH. All the extracts were non-mutagenic in the absence of nitrosation. The nitrosated aqueous extract was mutagenic in strains TA98 and TA100. While weak mutagenicity was elicited by the nitrosated aqueous: ethanolic extract in TA100, the nitrosated ethanolic extract induced a 3-fold increase in the number of revertants in the same strain. Moreover both these extracts elicited a strong mutagenic response in TA102, while the chloroform extract was non-mutagenic even after nitrite treatment. The present study indicates that workers employed in the bidi industry are exposed to potentially mutagenic and genotoxic chemicals in the course of their occupation. PMID- 1922161 TI - The effects of ventilation and the dilution of smoke upon the clastogenic and aneugenic activity of tobacco particulate matter in cultured mammalian cells. AB - We demonstrate here that tobacco particulate matter (TPM) produced from both non ventilated and ventilated cigarettes of varying tar contents induced structural and numerical aberrations in cultured Chinese hamster cells. Our data indicate that TPM from ventilated cigarettes is of lower potency in inducing both clastogenic and aneugenic effects compared with TPM from non-ventilated cigarettes. These observations provide support for the concept that the genotoxic activity (to cultured Chinese hamster cells) of cigarette smoke is reduced by increased ventilation to a greater extent than a 1:1 ratio between yield reduction and smoke dilution. PMID- 1922162 TI - Potential negative regulation of damage-recognition proteins in cisplatin resistant HeLa cells in response to DNA damage. AB - Nuclear proteins in cisplatin-resistant (CPR) and non-resistant HeLa cells were assayed by 2-dimensional polyacrylamide gel electrophoresis. The levels of at least 4 suppressible nuclear proteins were reduced in CPR cells. These proteins were partially restored in CPR revertants that are known to be less capable of repairing cisplatin-DNA adducts. Southwestern blotting assays indicate that in CPR cells at least 1 DNA-binding protein was suppressed, and concomitantly with it several damage-recognition proteins (DRPs) were induced. In addition, gel mobility shift analysis shows that DRPs were overexpressed in CPR cells. These results suggest a potential negative regulation in normal cells that may be important for the induction of DRPs and the emergence of a repair-mediated CPR phenotype. PMID- 1922163 TI - Preparation of mouse-sperm DNA for PCR. PMID- 1922164 TI - Evaluation of DNA damage induced by norfloxacin in liver and kidney of adult rats and in fetal tissues after transplacental exposure. AB - Norfloxacin, a recently developed antimicrobial fluoroquinolone, was investigated for DNA-damaging activity in rat liver and kidney. After oral administration of single doses ranging from 1 to 8 mmole/kg, DNA fragmentation was absent in liver and kidney both 2 and 6 h after treatment. However, when administered to pregnant rats, the highest doses produced a detectable amount of DNA damage in fetal tissues. This damage appears to be an aspecific consequence of maternal and fetal toxicity rather than a specific genotoxic effect. PMID- 1922165 TI - Invited review: motor unit estimation: methods, results, and present status. AB - The renewed interest in motor unit estimation (counting) has coincided with the introduction of computer-based methodology and with the application of the technique to proximal as well as distal muscles. The advantages and disadvantages of the different methods are considered, together with the assumptions inherent in this type of examination. In normal subjects, the extensor digitorum brevis (EDB) muscle has approximately 200 motor units while each of the intrinsic muscles of the hand has about 100 units; larger muscles in the limbs contain greater numbers of units. Beyond the age of 60 years, there is a decline in the number of functioning motor units in both proximal and distal muscles. In denervating disorders, motor unit estimation is useful for diagnosis and assessment; abnormal values may often be observed in muscles judged clinically to be unaffected. Serial studies have enabled the rate of motor unit loss to be determined in ALS and in spinal muscular atrophy. Depletion of motor units has also been found following upper motoneuron lesions caused by injury to the spinal cord or by cerebral hemorrhage; trans-synaptic dysfunction has been presumed responsible. Rather surprisingly, reduced numbers of motor units have been observed in a variety of myopathic disorders; of these, the most consistent abnormalities have been reported in myotonic muscular dystrophy. PMID- 1922166 TI - Carnitine in muscle, serum, and urine of nonprofessional athletes: effects of physical exercise, training, and L-carnitine administration. AB - Efficient utilization of fatty acids to sustain prolonged physical efforts is thought to be dependent on the carnitine shuttle of muscle. A study has been carried out in 24 athletes (13 long-distance runners and 11 sprinters). These subjects received placebo or L-carnitine (1 g/orally b.i.d.) during a 6-month period of training. In endurance athletes, training induced lowering of total and free muscle carnitine. Increase of esterified muscle carnitine was also observed. Post-exertional overflow of acetylcarnitine and long-chain acylcarnitine, as well as reduction of the free fraction was also noticed in the blood. Fasting plasma carnitine levels, however, were not affected in carnitine-treated athletes at rest. These changes were likely related with the significantly increased urinary excretion of esterified and total carnitine which occurred after physical exercise. In the sprinters only, a decrease in free and total carnitine of muscle was detected after training. Both these potentially unfavorable effects were prevented by oral administration of L-carnitine. Our data suggest that training in endurance athletes, and to a lesser extent, in sprinters, is associated with a decrease in free and total carnitine of muscle, due to an increased overflow of short-chain carnitine esters in urine. PMID- 1922167 TI - AAEM Minimonograph #10: volume conduction. AB - A volume conductor is any medium with the capability of passively conducting a current between regions of potential difference. The monophasic positive intracellular action potential produces a monophasic negative extracellular waveform and a triphasic extracellular waveform in a poor and good volume conductor, respectively. The observed waveform characteristics are dependent upon both the recording electrode montage and the type of volume conductor surrounding the excitable tissue. The extracellular current flow associated with an action potential can be divided into two current sources flanking a central current sink. If a recording electrode is located over the negative current sink, a negative potential is observed. When the two current sources approach a recording electrode, a positive potential is recorded. If a positive deflection of the baseline is observed, one may conclude that the wave of depolarization under investigation did not originate under, but traveled toward, the recording location. Electric currents from external sources are free to propagate extraneurally as the body is a good volume conductor. Care must be taken to not activate nearby nerves and, subsequently, obtain a waveform contaminated with potentials from undesired sources. Additionally, electrical activity from neighboring muscles and nerves can summate in the volume conductor and yield responses capable of masking pathology. An understanding of the principles of volume conduction theory can help the electrodiagnostician avoid artifactual errors and erroneous conclusions. PMID- 1922168 TI - Type 2 fiber predominance in Lambert-Eaton myasthenic syndrome. AB - Serial muscle biopsies in a noncarcinomatous case of Lambert-Eaton myasthenic syndrome (LEMS) have shown progressive atrophy and loss of type 1 fibers, resulting in overwhelming type 2 predominance. A similar abnormality was found in a single biopsy from a second case of LEMS without associated carcinoma. Review of the literature suggests that type 2 fiber predominance has been observed in at least one other biopsied case. Interference with transmitter release caused by anti-voltage-gated calcium channel antibodies may deprive type 1 muscle fibers of the low frequency discharge necessary to maintain their metabolic properties. PMID- 1922169 TI - Acute peripheral arterial occlusion: electrophysiologic study of 32 cases. AB - Thirty patients with 32 acute peripheral arterial occlusions underwent nerve conduction and electromyographic studies at a mean of 12.4 months after the vascular occlusion. Compound action potentials showed greater reduction than conduction velocity (26% to 75% vs 8% to 13% lower than normal). All changes were more prominent in the legs than arms, including fibrillation potentials (64% vs 28%). Short motor unit potentials were seen in 13% of patients; this group also had signs of severe nerve damage. The extent of abnormality varied with location of occlusion. Signs of nerve damage were significantly decreased in patients who had early revascularization. The electrophysiologic findings suggested axonal destruction rather than demyelination. PMID- 1922170 TI - TEA-sensitive potassium channels and inward rectification in regenerated rat sciatic nerve. AB - Sucrose gap and intra-axonal recording techniques were used to identify the types of ion channels and inward rectification that are present in regenerated axons of adult (greater than 8 weeks) rat sciatic nerve after crush injury. In sucrose gap recordings, 4-aminopyridine (4-AP) led to slight broadening of the compound action potential (CAP) in normal nerve, and a greater broadening in regenerated nerves. By 12 days after sciatic nerve crush, regenerated nerves manifested an afterhyperpolarization (AHP) lasting up to 250 ms that was sensitive to tetraethylammonium (TEA). A similar TEA-sensitive AHP could be elicited with repetitive stimulation. Hyperpolarizing constant current steps (0.1 to 0.5 mA; 600-900 ms duration) applied across the sucrose gap through regenerated axons evoked membrane hyperpolarizations with a depolarizing, Cs(+)-sensitive relaxation in the response to hyperpolarization, which is characteristic of inward rectification, occurring after about 70 ms. The relaxation was present as early as 21 days after nerve crush. Intra-axonal recordings showed burst firing in 4-AP that was terminated by an AHP that temporally correlated with the TEA sensitive AHP, and a relaxation in the response to hyperpolarizing current, similar to that of whole nerve recordings. The results demonstrate that in addition to voltage-sensitive sodium channels and 4-AP-sensitive potassium channels, there are TEA-sensitive and inwardly rectifying channels on mammalian regenerated peripheral nerve axons. PMID- 1922171 TI - Normal maximal and minimal motor nerve conduction velocities in adults determined by a collision method. AB - Using a new collision method, we measured motor nerve conduction velocities of the ulnar nerve in the forearm and the action potential amplitude of the abductor digiti minimi muscle on 60 adults, ages 20 to 82 years and apparently free from diseases of the peripheral nervous system. Both maximal and minimal motor nerve conduction velocities were linear functions of age; 64.42-0.05 age and 60.45-0.12 age, respectively. The percentage of the minimal to the maximal motor nerve conduction velocities was expressed as 94.45-0.13 age. The maximum amplitude of evoked muscle action potentials was also correlated with age. This novel method may be useful in detecting pathology of motor nerve fibers which results in a decrease in submaximal conduction velocities. PMID- 1922172 TI - Real-time sonography of acute and chronic muscle denervation. AB - Presented are real-time ultrasound findings in partially and completely denervated muscles of 30 patients with focal neuropathy and various other disorders of the second motor neuron. Sonographic scans of affected muscles are analyzed in conjunction with unaffected muscles of the same individual, under identical examination conditions. Initial pathological ultrasound changes could be detected as soon as 2 weeks after an acute neurogenic lesion. In denervation, the echodensity of the muscle was high and the normal intramuscular pattern was decomposed. Findings were more intense in severe and longstanding denervation. Ultrasound-indicated pathology correlated highly (chi-square: P less than 0.001) with pathological spontaneous activity detected by electromyography. Focal and systemic neuropathies showed no differences in ultrasound pathology. Six cases with central motor palsy had normal sonograms. Poor spatial resolution of real time ultrasonography--as compared with CT and MRI--is compensated by its bedside availability, frequent repeatability without patient risk and discomfort, and its in vivo correlation of muscle morphology with muscle function. PMID- 1922173 TI - Distant effects of locally injected botulinum toxin: a double-blind study of single fiber EMG changes. AB - We used single fiber electromyography (SFEMG) to study 42 patients who had enrolled in a double-blind, placebo-controlled trial undertaken to assess the efficacy of botulinum toxin (BTX) injection of neck muscles to treat torticollis. SFEMG in a limb muscle was performed before treatment, 2, and 12 weeks after injection of placebo or BTX. Before treatment, the mean jitter was 26.8 microsec in patients who were to receive BTX, and 25.7 microsec in the placebo group. Two weeks after injection, mean jitter in the group receiving BTX was 43.6 microsec. In the placebo group, it was 26.5 microsec (P = less than .05). Twelve weeks after injection, mean jitter in the BTX group was 35.5; for the placebo group it was 24.5. Fiber density did not change in any patient during the study. There were no remote clinical effects of BTX. Injection of BTX into muscles affected with focal dystonia is a promising and safe treatment, but there are subclinical effects on uninjected muscles. PMID- 1922174 TI - Hypertriglyceridemia in carnitine palmityl transferase deficiency: lipid profile and treatment with medium chain triglycerides. PMID- 1922175 TI - Concentric macro electromyography. AB - Concentric EMG electrodes can record from a few (10 to 15) muscle fibers of a motor unit (MU). Macro EMG, is able to record from the majority of muscle fibers in the MU. The macro EMG electrode uses a single fiber action potential (SFAP) on one channel to trigger the time locked cannula (macro) response on the other channel. To study the concentric motor unit action potential (MUAP), alongside the macro potential, we built a needle electrode combining concentric and macro recording surfaces. The study of 240 motor units in 10 healthy subjects with the single fiber (SF macro) and concentric macro (conmac) electrodes revealed no significant differences between macro potentials areas and amplitudes obtained with either electrode. The ability to study a small and a large section of the motor unit simultaneously offers insights into the local or global nature of motor unit changes not otherwise available to the electromyographer. It also reveals which concentric parameters correlate best with the macro potential and, can even be of great help with the newer EMG signal decomposition techniques; by identifying each motor unit by its concentric and macro waveform simultaneously, it will allow for the "marking" of these motor units helping to reduce the risk of their misclassification when the concentric MUAP is used alone. PMID- 1922176 TI - "Smoothed histograms": a visual aid for the analysis of distributions of muscle fiber areas. AB - The Kernel Density Estimator (KDE) is a versatile nonparametric technique with very good theoretical properties. It is used to obtain "smoothed histograms," which allows several distributions to be presented and analyzed more easily on one graph, and direct combination into average distributions. The application of the KDE method as a visual aid for the analysis of distributions of muscle fiber areas is presented here. PMID- 1922177 TI - Fatigue in type I fiber predominance: a muscle force and surface EMG study on the relative role of type I and type II muscle fibers. AB - The relative proportions of fiber types within muscle and the characteristics of these fiber types are important determinants of the surface electromyogram (SEMG) during fatigue. In this study, patients suffering from congenital myopathy characterized by a strong type I fiber predominance were studied. Six patients with 95-100% type I fibers, 2 patients with 80% type I fibers, and 12 healthy volunteers participated in an ischemic, isomeric, intermittent exercise test of m. quadriceps femoris at 80% MVC. Considering the results of the morphometric analysis of muscle biopsy specimen and of the anthropometric estimated muscle bone volume, it was found that type I muscle fibers had a lower force generating capacity than type II fibers. The initial conduction velocity along the muscle fiber membrane (MFCV) was low in patients with 95-100% type I fibers. During the ischemic exercise test, the 95-100% type I fibers showed less fatigability than type II fibers, which was reflected by a nearby absent decrease of the muscle membrane excitability as measured by the MFCV, and only a slight increase of the SEMG amplitude compared with patients having 80% type I fibers and controls. The absence of a definite MFCV decrease was related to the nearby lacking lactate formation in 95-100% type I fibers. PMID- 1922178 TI - Calcium-tension relationships of muscle fibers from patients with periodic paralysis. AB - Lateral gastrocnemius muscle biopsies from a 26-year-old man with hyperkalemic periodic paralysis and a 23-year-old man with hypokalemic periodic paralysis were studied. Both patients came from families in which older relatives had developed a vacuolar myopathy in association with their periodic paralysis. Muscle fibers were chemically skinned, and individual fibers were studied with a low-compliance strain gauge. The tension generated by fibers was studied in baths with calcium concentrations from 10(-8) mol/L to 2.5 x 10(-5) mol/L. The Ca-tension relationships and maximal tensions (normalized to fiber cross-sectional area) of fast and slow twitch fibers were indistinguishable from those found in fibers from 5 normal subjects. The results reinforce earlier findings which suggested that loss of Ca-induced myofibril contraction was not the cause of paralysis in periodic paralysis. PMID- 1922179 TI - Dorsal nerve of the penis nerve conduction velocity: a new technique. AB - In the evaluation of a possible peripheral neuropathic process as the etiology of erectile dysfunction, studies of the dorsal nerve of the penis may be unique in that they allow examination of the most distal segment of pudendal nerve in isolation. This study describes a new technique using a simple traction device for elongation of the penis to determine the orthodromic nerve conduction of the dorsal nerve of the penis. With stimulation at the glans, and recording at the base of the penis, the value obtained in 20 normal subjects was 36.2 +/- 3.2 m/s with an amplitude of 2.29 +/- 1.08 mV. PMID- 1922180 TI - Use of a catchlike property of human skeletal muscle to reduce fatigue. AB - This study compared the force output produced by variable frequency, short duration trains (VFTs) of electrical pulses with the forces produced by constant frequency, short-duration trains (CFTs). Human quadriceps femoris muscle was stimulated with a 300-msec train of pulses once every second for 180 seconds. Each subject (n = 12) participated in 4 randomly assigned experimental sessions. During 3 sessions, a CFT of 80, 40 or 20 pps was used. During a fourth session, a VFT, which consisted of all 3 of the above frequencies, was used. The force at 100 msec, average force of each contraction and peak force were calculated for every 30th contraction. By the 90th contraction, the force at 100 msec and the average force were significantly greater for the VFT than for each CFT. Thus, the VFT, by using a catchlike property, may provide significant advantages over any CFT when using electrical stimulation for functional electrical stimulation. PMID- 1922181 TI - Conduction block in diabetic neuropathy. AB - Symmetric sensorimotor polyneuropathy is a common complication of diabetes. Sensory and motor evoked amplitudes and conduction velocities are reduced. Both demyelination and axon loss have been reported in pathologic studies. Conduction block (CB), a manifestation of segmental demyelination, has not been previously studied in diabetic neuropathy. We determined the prevalence of conduction block in patients with diabetes by analyzing electrodiagnostic data from 24 diabetics. Conduction block was defined as a greater than 20% drop in peak-to-peak amplitude, and a less than 15% change in negative-peak duration between proximal and distal stimulation sites. A total of 76 nerve segments were studied. The criteria for conduction block were met in only 6 segments in 6 patients. The mean decrease in peak-to-peak amplitude between stimulation sites was 28% (range 21% to 40%). We conclude that conduction block over long nerve segments is uncommon in diabetic neuropathy, and, if present, suggests that other causes for neuropathy in diabetic patients should be sought. PMID- 1922182 TI - Paradoxical lid elevation with sustained upgaze: a sign of Lambert-Eaton syndrome. AB - Myasthenia gravis and Lambert-Eaton myasthenic syndrome are causes of acquired extraocular muscle weakness and ptosis. Exacerbation of ptosis after sustained upgaze is a clinically useful sign in the diagnosis of myasthenia gravis. A 54 year-old woman with established Lambert-Eaton myasthenic syndrome exhibited transient improvement of her ptosis after sustained upgaze. We suggest that paradoxical lid elevation after sustained upgaze may be a clinically useful sign in distinguishing Lambert-Eaton myasthenic syndrome from myasthenia gravis. PMID- 1922183 TI - Conduction block in clinical practice. PMID- 1922184 TI - The medically important dematiaceous fungi and their identification. AB - Dematiaceous fungi include a large group of organisms that are darkly pigmented (dark brown, olivaceous, or black). In most cases the pigment is melanin, and specifically, dihydroxynaphthalene melanin. The diseases produced include chromoblastomycosis, eumycotic mycetoma, and phaeohyphomycosis. Phaeohyphomycosis is a new classification for a diverse group of previously known entities grouped together on the basis of finding dematiaceous hyphal and/or yeast-like forms in tissue; tissue involvement may be superficial, cutaneous and corneal, subcutaneous, or systemic. Identification of these fungi is based mostly upon morphology. Important structures include annellides (Phaeoannellomyces, Exophiala), phialides (Phialophora, Wangiella), adelophialides (Phialemonium without collarettes, Lecythophora with collarettes), differentiation of conidiophores (Xylohypha versus Cladosporium) and conidial hilum, septation and germination (Bipolaris, Drechslera, Exserohilum). Useful laboratory tests include the 12% gelatin test (controversial), nitrate assimilation (W. dermatitidis is negative, most other species are positive), and determination of temperature maxima (especially 37 degrees C for E. jeanselmei, 40 degrees C for W. dermatitidis and B. spicifera, 42 degrees C for X. bantiana, and 45 degrees C for Dactylaria constricta var. gallopava and Scedosporium inflatum). PMID- 1922185 TI - The antigenic composition and protein profiles of eumycetoma agents. AB - The protein profiles of different eumycetoma agents were compared by SDS gel electrophoresis. Dendrograms confirmed the homogeneity of isolates of Pseudallescheria boydii but amongst Madurella species, particularly isolates identified as M. grisea, there were substantial differences in protein composition. However using Western blotting reference isolates of the different species showed distinct antigen patterns in response to immune rabbit sera. In particular there was little evidence of cross reactivity between M. mycetomatis and M. grisea. However this specificity was not apparent when human sera from patients with different eumycetoma infections were compared in an ELISA system using the same antigens. It is possible that the formation of a mycetoma grain may limit a patient's exposure to antigens which confer specificity, an explanation which may also account for the variability in antibody responses seen. PMID- 1922186 TI - Serum-independent neutrophil chemotaxins in the yeast phase of Candida albicans. AB - Cell extracts from 6 strains of Candida albicans grown under different conditions were partially purified and tested for inherent chemotactic activity for human polymorphonuclear granulocytes. Chemotactic activity was demonstrated in the absence of serum using the Boyden chamber technique. No chemokinetic effects of the extracts examined were found using the same method. Cross desensitization experiments of PMN with C. albicans extracts and known leukotaxins (PAF, LTB4, and FMLP) revealed that C. albicans-derived chemotaxins differed from the known chemoattractants. Their possible role in Candida infections is discussed. PMID- 1922187 TI - Modulation of leukotriene metabolism from human polymorphonuclear granulocytes by bifonazole. AB - The influence of bifonazole and other azoles on the leukotriene-metabolism of human neutrophil granulocytes (PMN) was investigated. The cells were stimulated with the Ca-ionophore A23187 over 15 minutes in the presence of the azoles. Subsequently the supernatants were analyzed for their leukotriene content by reversed-phase HPLC. In order to confirm that the observed effects are not due to cytotoxic phenomena tests were performed to evaluate the viability of the granulocytes. The chemotactic active leukotriene B4 (LTB4) and its inactive omega metabolites were detected and quantified by HPLC analysis. The results clearly demonstrated that bifonazole inhibited the omega-oxidation already at concentrations as low as 0.5 microgram ml-1. As a consequence the LTB4-level became elevated. At concentrations up to 64 micrograms ml-1 bifonazole totally blocked the formation of leukotrienes in human granulocytes. Identical experiments were performed with other azoles and with various anti-inflammatory drugs just to have a comparison with bifonazole. It is evident that bifonazole in addition to its well known antimycotic action shows a unique modulation of the leukotriene-metabolism, which is important for its anti-inflammatory potency. PMID- 1922188 TI - Pathogenesis of postoperative candidosis: no detectable fungemia during reoperations after abdominal surgery. AB - Pathogenesis of systemic candidosis in surgical patients is unsettled. Results from animal models suggest that invasion from colonized intestine is the major portal of entry into circulation. To study the mechanisms of systemic candidosis in surgical patients after intestinal surgery, multiple blood cultures were taken during reoperations with manipulation of the intestinum to detect possible perioperative fungemia. The lysis centrifugation method (Isolator) was used for blood cultures. Of the 30 subjects in the material, 12 were demonstrated to be colonized with yeast before the reoperation. Three patients had positive blood cultures during reoperation, but no yeasts were found in the 146 perioperative blood cultures. Three patients had severe nonsuperficial yeast infection after reoperation, but none had disseminated candidosis. This finding in high risk patients supports the view that immediate perioperative fungemia and persorption from colonized intestinum is rare. However, persorption may occur later via healing wounds of the colonized intestinum. Both persorption and the exogenous route (e.g. vascular catheters) are possible in the pathogenesis of postoperative candidosis. PMID- 1922189 TI - Fatty acid analysis of different Candida species by capillary column gas-liquid chromatography. AB - Gas-liquid chromatography was used to analyse the fatty acid composition of whole cell hydrolysates of 40 yeast strains representing 5 Candida species and Torulopsis glabrata, T. glabrata could be easily distinguished from all other Candida spp. by the absence of C18:3. Candida albicans, C. krusei, C. parapsilosis, C. pseudotropicalis and C. tropicalis showed 10 major peaks in characteristic proportions. C. parapsilosis showed a high C16:0/C16:1 ratio (greater than 4.5), whereas C. pseudotropicalis was characterized by a C18:1/C16:0 ratio of less than 2.0. A high C18:3 concentration (greater than 10%) was typical for C. krusei (C18:2/C18:3 ratio less than or equal to 1.0). Our data reveal characteristic patterns of cellular fatty acid composition of T. glabrata, C. krusei, C. parapsilosis and C. pseudotropicalis which can be used for laboratory identification. PMID- 1922190 TI - African histoplasmosis in a Belgian AIDS patient. AB - We describe an African histoplasmosis case in a 65-year-old Belgian living in Zaire for 46 years. Microscopic bone marrow examination showed Histoplasma. It was confirmed by cultures and hamster inoculation. Autopsy revealed a fungal dissemination by Histoplasma duboisii. PMID- 1922191 TI - Cryptococcal meningoencephalitis in a patient with Hodgkin's lymphoma: successful treatment with fluconazole. AB - The authors report a case of cryptococcal meningoencephalitis in a 22-year-old male with Hodgkin's disease at third stage B. Cryptococcus neoformans was isolated from cerebral spinal fluid (CSF) and blood specimens. Latex antigen agglutination tests and India ink preparations also were positive for this pathogenic yeast. Drug treatment for a week with 20 mg i.v./day of amphotericin B in combination with 2.5 g i.v./day of 5-fluorocytosine did not lead to any improvement in the patient. The patient became asymptomatic after the first week of treatment with a daily dose of 400 mg of fluconazole, administered intravenously. After two months of this regimen, all laboratory tests on CSF and blood specimens were negative. PMID- 1922192 TI - Glycosidic activities of Candida albicans after action of vegetable latex saps (natural antifungals) and isoconazole (synthetic antifungal). AB - Glycosidic activities have been examined in Candida albicans grown on medium culture containing latex sap (natural antifungal) or isoconazole (synthetic antifungal). The different types of utilized latex sap were those of Lactuca sativa (latex exuded from articulated laticifers) and Asclepias curassavica (latex flowing from non-articulated laticifers). The same enzyme assays were performed on C. albicans grown without antifungal compounds. Except for alpha arabinosidase, all glycosidase activities were increased when C. albicans was grown in medium supplemented with L. sativa latex sap. The most stimulated activities were those of beta-fucosidase, alpha-galactosidase, alpha- and beta glucosidase, alpha- and beta-mannosidase, acetyl-beta-glucosaminidase. The presence of A. curassavica latex sap in culture medium produced similar results: the most stimulated activities were those of alpha-mannosidase, alpha galactosidase, acetyl-beta-glucosaminidase and beta-fucosidase. Electron microscope observations suggested a correlation between this stimulation of glycosidic activities and the fungal cell wall breakdown. For comparison the presence of isoconazole in culture medium yields no increase in glycosidic activities and no ultrastructural modification of fungal cell wall. The mode of action of latex saps in cell wall breakdown is discussed. PMID- 1922193 TI - Polyene resistance in ergosterol producing strains of Candida albicans. AB - Following nitrous acid mutagenesis, one nystatin- (nyl) and two amphotericin B (AB)-resistant (ab1 and ab2) mutants of Candida albicans were isolated and characterized. The three mutants plus a previously described cytochrome P450 deficient mutant (D10) of this organism were analyzed for polyene cross resistance. Cross resistance was noted for ny1 and D10 but not for ab1 and ab2. Sterol analysis indicated that ny1 was a delta 8-delta 7 isomerase mutant while ab1 and ab2 showed wild type sterol profiles. Fatty acid analysis showed no significant differences for ab1, ab2, and ny1 compared to wild type while D10 showed more pronounced differences. AB- and Triton X-100-induced potassium leakage studies indicated that ab1 and ab2 are resistant to low AB levels and ny1 is resistant to higher AB levels. In contrast, ab1 and ab2 were more resistant to detergent-induced potassium leakage than the wild type or mutants ny1 and D10. Significant differences in growth rate, ethanol sensitivity, and response to Tergitol were also noted among the resistant strains. The data indicate a different mechanism of action for the two polyenes and indicate a resistance mechanism for ab1 and ab2 based on subtle alterations of membrane structure rather than sterol substitution. PMID- 1922194 TI - Single dose treatment of vaginal candidosis: randomised comparison of amorolfine (50 mg and 100 mg) and clotrimazole (500 mg) in patients with vulvovaginal candidosis. AB - A double blind randomised comparative study of single dose treatment with amorolfine vaginal tablets (50 mg and 100 mg) and clotrimazole 500 mg monodose vaginal tablets (open labelled) was undertaken in patients with vaginal candidosis. Vaginitis was demonstrated by both a positive culture and positive findings on microscopic examination of a vaginal smear as well as by the presence of clinical symptoms. 118 patients seen over a 6 month period were randomly allocated to receive one 50 mg vaginal tablet of amorolfine (regimen A, 40 patients), a 100 mg vaginal tablet of amorolfine (regimen B, 38 patients) or a 500 mg tablet of clotrimazole (regimen C, 40 patients). At the assessment one week after the end of therapy the proportion of cured patients was 90% in group A, 94.7% in group B and 92.5% in group C. 4 patients (10%) in group A, 2 (5.2%) in group B and 3 (7.5%) in group C did not respond to the treatment. There was a significant association between Candida glabrata and treatment failure (P less than 0.001) and C. glabrata and carrier state (P less than 0.01). At the assessment 4 weeks after the end of therapy the proportion of cured patients was 80% in group A, 84.2% in group B and 67.5% in group C with a relapse rate of 10% (group A), 10.5% (group B) and 25% (group C). C. glabrata was significantly associated with non-effective overall treatment (P less than 0.05). The relapse rate was significantly associated with positive culture results one week post therapy (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922195 TI - Sequence of a small subunit rRNA gene of Schistosoma mansoni and its use in phylogenetic analysis. AB - The complete sequence of a small ribosomal RNA gene of Schistosoma mansoni contained within plasmids pSM389 and pSM889 is presented. It was found to be 1992 bp in length, larger than that of most eukaryotes. Extra nucleotides occur in regions known to be variable (V4 and V7). The predicted secondary structure of the nucleotides 660-853 revealed additional helices which have been designated E21-1A and E21-1B. The other region to differ from higher eukaryotes lies between nucleotides 1457 and 1569. Secondary structure prediction demonstrated that a single extended helix may be formed from this part of the schistosome small subunit rRNA sequence. Nucleotides that could be unambiguously aligned with those of 12 other eukaryotes were used to estimate phylogenetic relationships. The consensus tree obtained by Maximum Parsimony analysis showed the schistosome as a sister taxon to the flatworm Dugesia tigrina. PMID- 1922196 TI - The spliced leader gene of Angiostrongylus cantonensis. AB - A 5' leader sequence has been identified on mRNAs of the parasitic nematode Angiostrongylus cantonensis. A 720-bp XhoI restriction fragment containing the gene encoding the leader sequence has been cloned and sequenced. It contains a 22 nt sequence identical to that of the leader sequence of Caenorhabditis elegans, a consensus splice site and a putative Sm antigen binding site. The gene is present as a tandem repeating unit of approximately 60 copies, and unlike C. elegans it is not associated with the 5S ribosomal RNA gene. The SL-RNA is 110 nt long and the sequence and primer extension studies suggest that it is transcribed from the tandemly repeating SL gene. It is precipitable from cell-free extracts of adult nematodes by anti-Sm anti-sera, and from RNA by anti-TMG anti-sera, thus suggesting its inclusion with small nuclear ribonucleoproteins in RNA splicing. PMID- 1922197 TI - cDNA clones of Onchocerca volvulus low molecular weight antigens provide immunologically specific diagnostic probes. AB - We report here a panel of cDNA clones from Onchocerca volvulus which were isolated on the basis of being uniquely recognised by onchocerciasis sera and not by sera from patients infected with the major lymphatic filarial nematode parasite Wuchereria bancrofti. Over 90% of O. volvulus recombinants from a primary screen were found to cross-react with lymphatic filariasis sera and were discarded. The subset of specific clones, selected with pooled sera, was then screened with panels of individual patient sera. Individual onchocerciasis cases showed a highly heterogeneous pattern of recognition of recombinant peptides, but several clones were identified which could be combined in a cocktail of antigenic epitopes to successfully detect all infected cases in the study. All these clones encode low molecular weight proteins of the parasite, confirming earlier reports that antigens of this size class show greater species specificity. Several clones encode proteins of 20-23 kDa, the same molecular weight range as the major surface protein of adult worms. The two most commonly recognised clones, Ov22/31M and Ov20/36M were subcloned into the vector pNGS 8 which produces fusion proteins attached to a polyasparagine leader. The fusion peptides of both Ov22/31M and Ov20/36M were soluble and easily purified by gel filtration. Purified fusion protein was used in ELISA to assess reactivity of infected patients giving 90% sensitivity with 100% specificity. PMID- 1922198 TI - An mRNA-dependent in vitro translation system from Trypanosoma brucei. AB - We have demonstrated efficient protein synthesis in a cell-free system from the bloodstream form of Trypanosoma brucei. This system was able to translate endogenous mRNA, added mRNA, or (apparently at much lower efficiency) three synthetic RNA transcripts lacking 5' mini-exon and 3' poly(A) sequences. Translation was resistant to chloramphenicol and greater than 95% inhibited by low concentrations of anisomycin and puromycin, but only partially inhibited by cycloheximide. Variant surface glycoprotein synthesized from endogenous mRNA was sensitive to endoglycosidase H, indicating the co-translational glycosylation potential of the system. Two proteins translated ab initio from the corresponding in vitro-transcribed RNAs showed no evidence of signal sequence cleavage or glycosylation. Efficient processing occurred when the same RNAs were translated in a rabbit reticulocyte lysate supplemented with canine pancreatic microsomes but not with trypanosome microsomes. PMID- 1922199 TI - Cloning and restriction enzyme mapping of ribosomal DNA of Giardia duodenalis, Giardia ardeae and Giardia muris. AB - In an attempt to study Giardia at the DNA sequence level, the rRNA genes of three species, Giardia duodenalis, Giardia ardeae and Giardia muris were cloned and restriction enzyme maps were constructed. The rDNA repeats of these Giardia show completely different restriction enzyme recognition patterns. The size of the rDNA repeat ranges from approximately 5.6 kb in G. duodenalis to 7.6 kb in both G. muris and G. ardeae. These size differences are mainly attributable to the variation in length of the spacer. Minor differences exist among these Giardia in the sizes of their small subunit rRNA and the internal transcribed spacer between small and large subunit rRNA. The genetic maps were constructed by sequence analysis of the DNA around the 5' and 3' ends of the mature rRNA genes and between the rRNA covering the 5.8S rRNA gene and internal transcribed spacer. Comparison of the 5.8S rDNA and 3' end of large subunit rDNA from these three Giardia species showed considerable sequence variation, but the rDNA sequences of G. duodenalis and G. ardeae appear more closely related to each other than to G. muris. PMID- 1922200 TI - Long-range restriction maps of size-variable homologous chromosomes in Leishmania infantum. AB - In order to clarify the interpretation of molecular karyotype polymorphisms in Leishmania, the three smallest chromosomes from five cloned strains of Leishmania infantum were identified by chromosome-specific anonymous DNA probes. The presence in the same clone of homologous chromosomes of a different size was demonstrated. The chromosome size polymorphism appeared even more dramatic, with size variations affecting up to 20% of the chromosome, and the two smallest bands in one strain being equivalent to six bands in another strain. Long-range restriction maps of five different-sized homologues of chromosome I showed the size-variation to be located to a terminal fragment in 4 out of 5 cases, and to a central fragment in one. The size-variable sequence was present on at least three other chromosomes as determined by hybridisation analysis. This suggests an instability of the subtelomeric regions such as that in Plasmodium falciparum. Lastly, the finding of several pairs of distinct-sized homologous chromosomes, together with other studies, strongly suggest that Leishmania is diploid in at least part of its chromosomal complement. PMID- 1922201 TI - Trichomonas vaginalis hydrogenosomal proteins are synthesized on free polyribosomes and may undergo processing upon maturation. PMID- 1922202 TI - Minimal variation in Pfs16, a novel protein located in the membrane of gametes and sporozoites of Plasmodium falciparum. PMID- 1922203 TI - Analysis of MSA-1 diversity in Plasmodium chabaudi chabaudi strains. PMID- 1922204 TI - Partial sequences of three new asparagine-rich blood stage proteins of Plasmodium falciparum. PMID- 1922205 TI - Prevention of postmenopausal osteoporosis. A comparative study of exercise, calcium supplementation, and hormone-replacement therapy. AB - BACKGROUND: Osteoporosis among older women is a major public health problem. We studied the effects of three approaches to the prevention of osteoporosis in women with low bone density. METHODS: One hundred twenty postmenopausal women (mean [+/- SD] age, 56 +/- 4) who were selected because they had low forearm bone density were enrolled in a double-blind, placebo-controlled, randomized study comparing the effects of an exercise regimen (exercise group, n = 41), exercise plus dietary calcium supplementation (exercise-calcium group, n = 39), and exercise plus continuous replacement of estrogen and progesterone (exercise estrogen group, n = 40). Periodically during the two-year study period, we measured the women's bone density at three forearm sites, measured indexes of calcium metabolism, and recorded symptom scores. A comparison group of 42 women (mean age, 55.5 +/- 3.1) with normal bone density was also followed for two years. RESULTS: Significant bone loss in the distal forearm occurred in the group with normal bone density (control group) and the exercise group (change, -2.7 percent and -2.6 percent of the base-line value per year, respectively). Bone loss at the distal forearm site was significantly lower in the exercise-calcium group (-0.5 percent of the base-line value per year), and bone density increased at this site in the exercise-estrogen group (+2.7 percent of the base-line value per year). Bone loss at the median forearm site was significantly lower in the exercise-calcium group (-1.3 percent of the base-line value per year) than in the exercise group (-2.4 percent), and bone density at this site increased significantly in the exercise-estrogen group (+0.8 percent of the base-line value per year). Breast tenderness occurred in 47 percent of the women in the exercise estrogen group but in only 20 percent in the other two treatment groups. Vaginal bleeding occurred at some time in 52 percent of the women who had not had a hysterectomy in the exercise-estrogen group, as compared with 11 percent and 12.5 percent, respectively, in the exercise and exercise-calcium groups. CONCLUSIONS: In postmenopausal women with low bone density, bone loss can be slowed or prevented by exercise plus calcium supplementation or estrogen-progesterone replacement. Although the exercise-estrogen regimen was more effective than exercise and calcium supplementation in increasing bone mass, it also caused more side effects. PMID- 1922206 TI - Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. AB - BACKGROUND: Postmenopausal estrogen-replacement therapy may reduce the risk of cardiovascular disease, and this beneficial effect may be mediated in part by favorable changes in plasma lipid levels. However, the effects on plasma lipoprotein levels of postmenopausal estrogens in the low doses currently used have not been precisely quantified, and the mechanism of these effects is unknown. METHODS: We conducted two randomized, double-blind crossover studies in healthy postmenopausal women who had normal lipid values at base line. In study 1, 31 women received placebo and conjugated estrogens at two doses (0.625 mg and 1.25 mg per day), each treatment for three months. In study 2, nine women received placebo, oral micronized estradiol (2 mg per day), and transdermal estradiol (0.1 mg twice a week), each treatment for six weeks. The metabolism of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was measured by endogenously labeling their protein component, apolipoprotein B. RESULTS: In study 1, the conjugated estrogens at doses of 0.625 mg per day and 1.25 mg per day decreased the mean LDL cholesterol level by 15 percent (95 percent confidence interval, 11 to 19 percent; P less than 0.0001) and 19 percent (95 percent confidence interval, 15 to 23 percent; P less than 0.0001), respectively; increased the HDL cholesterol level by 16 percent (95 percent confidence interval, 12 to 20 percent; P less than 0.0001) and 18 percent (95 percent confidence interval, 14 to 22 percent; P less than 0.0001), respectively; and increased VLDL triglyceride levels by 24 percent (95 percent confidence interval, 8 to 40 percent; P less than 0.003) and 42 percent (95 percent confidence interval, 26 to 58 percent; P less than 0.0001), respectively. In study 2, oral estradiol increased the mean concentration of large VLDL apolipoprotein B by 30 +/- 10 percent (P = 0.05) by increasing its production rate by 82 +/- 18 percent (P less than 0.01). Most of this additional large VLDL was cleared directly from the circulation and was not converted to small VLDL or LDL. Oral estradiol reduced LDL cholesterol concentrations by 14 +/- 3 percent (P less than 0.005), because LDL catabolism increased by 36 +/- 7 percent (P less than 0.005). The oral estradiol increased the HDL cholesterol level by 15 +/- 2 percent (P less than 0.0001). Transdermal estradiol had no effect. CONCLUSIONS: The postmenopausal use of oral estrogens in low doses favorably alters LDL and HDL levels that may protect women against atherosclerosis, while minimizing potentially adverse effects on triglyceride levels. The decrease in LDL levels results from accelerated LDL catabolism; the increase in triglyceride levels results from increased production of large, triglyceride-rich VLDL. PMID- 1922207 TI - A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guerin for transitional-cell carcinoma of the bladder. AB - BACKGROUND: In carcinoma of the bladder, both intravesical chemotherapy and immunotherapy can induce tumor regression and reduce the rate of recurrence, but the relative merits of these two therapies are unclear. We conducted a multi institutional study to address this question. METHODS: Patients with rapidly recurrent (stage Ta and T1) or in situ transitional-cell carcinoma of the bladder were randomly assigned to receive either doxorubicin administered intravesically or bacille Calmette-Guerin (BCG) administered both intravesically and percutaneously. The 262 eligible patients were followed for a median of 65 months. Complete responses to treatment of carcinoma in situ were confirmed by biopsy and cytologic analysis of the urine. RESULTS: For patients with Ta and T1 tumors without carcinoma in situ, the estimated probability of being disease free at five years was 17 percent after doxorubicin, as compared with 37 percent after immunotherapy with BCG (P = 0.015). The median times to treatment failure (termination of treatment, due to persistence, recurrence, or progression of disease) were 10.4 and 22.5 months, respectively. For patients with carcinoma in situ the complete-response probability estimates (i.e., the estimated probability of documented disappearance of disease) were 34 percent for doxorubicin (23 of 67 patients) and 70 percent for BCG (45 of 64 patients) (P less than 0.001); the median times to treatment failure were 5.1 and 39 months, respectively. The probability of being disease-free at five years survival among the patients with carcinoma in situ was 18 percent after treatment with doxorubicin and 45 percent after BCG therapy. Patients treated with BCG had a higher incidence of toxic systemic effects and a larger number of local irritative symptoms than patients treated with doxorubicin, but few of these adverse reactions were severe. CONCLUSIONS: As compared with intravesical doxorubicin, immunotherapy with BCG provides improved protection against the recurrence of superficial bladder cancer. PMID- 1922208 TI - Pretransplantation blood transfusion revisited. AB - BACKGROUND: Blood transfusion before organ transplantation has a beneficial effect on allograft survival; the mechanism of this effect has remained a mystery. In murine models, the presence of common histocompatibility antigens in the blood donor and the recipient favors the induction of allograft tolerance. METHODS: To investigate the effect of HLA compatibility between blood donor and recipient on the induction of allograft tolerance, we determined the relative frequency of cytotoxic T-lymphocyte precursors specific for donor cells before and at several times after blood transfusion in 23 patients awaiting a first renal transplant. We correlated the results with the presence of shared HLA antigens. RESULTS: T-cell nonresponsiveness against donor cells developed after blood transfusion in 10 of the 23 patients. Tolerance developed only if the blood donor and the recipient had one HLA haplotype or at least one HLA-B and one HLA DR antigen in common (as was observed in 9 of these 10 patients). Tolerance developed relatively late after blood transfusion (one to two months) and was long-lasting. No decline in the T-cell response against donor alloantigens was observed in any of the 13 patients who received transfusions without having HLA antigen compatibility with the donor. CONCLUSIONS: Blood transfusion in which there is a common HLA haplotype or shared HLA-B and HLA-DR antigens induces tolerance to donor antigens. This finding may lead to the development of new strategies with which to induce tolerance for transplantation after blood transfusion. Perhaps transplant donors will be selected not only by HLA-antigen matching, but also on the basis of acceptable HLA-antigen mismatches associated with T-cell non-responsiveness induced by selected blood transfusion. PMID- 1922209 TI - Gastrointestinal endoscopy (2) PMID- 1922210 TI - Licorice-induced hypermineralocorticoidism. PMID- 1922211 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1991. A 27-year-old man with AIDS, a cough, fever, and pulmonary infiltrates. PMID- 1922212 TI - Specific transplantation tolerance. PMID- 1922213 TI - Routine inquiry about organ donation--an alternative to presumed consent. PMID- 1922214 TI - Ruling out acute myocardial infarction. PMID- 1922215 TI - HIV-1 in seronegative homosexual men. PMID- 1922216 TI - Subdural blood patch for spinal headache. PMID- 1922217 TI - Mortality among workers exposed to ethylene oxide. PMID- 1922218 TI - Advance directives for medical care. PMID- 1922219 TI - Video-game therapy. PMID- 1922220 TI - A comparison of two doses of aspirin (30 mg vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. AB - BACKGROUND: Aspirin is known to improve the outcome of patients who have had a cerebral transient ischemic attack, but the optimal dose of aspirin remains uncertain. Experimental evidence indicates that 30 mg of aspirin daily alters platelet aggregation more favorably than the 300-mg dose currently used in patients after transient ischemic attack or minor ischemic stroke. METHODS: We assessed the effects of two doses of a water-soluble preparation of acetylsalicylic acid, or aspirin (30 mg vs. 283 mg a day), on the occurrence of death from all vascular causes, nonfatal stroke, or nonfatal myocardial infarction in a double-blind, randomized, controlled clinical trial in patients who had had a transient ischemic attack or minor stroke. A total of 3131 patients participated in the study. The mean follow-up was 2.6 years. RESULTS: In the group assigned to receive 30 mg of aspirin, the frequency of death from vascular causes, nonfatal stroke, or nonfatal myocardial infarction was 228 of 1555 (14.7 percent), as compared with 240 of 1576 (15.2 percent) in the group assigned to receive 283 mg. The age- and sex-adjusted hazard ratio for the group receiving the lower dose was 0.91 (95 percent confidence interval, 0.76 to 1.09). There were slightly fewer major bleeding complications in the 30-mg group than in the 283-mg group (40 vs. 53), and significantly fewer reports of minor bleeding (49 vs. 84). Fewer patients receiving 30 mg of aspirin reported gastrointestinal symptoms (164 vs. 179) and other adverse effects (73 vs. 90). CONCLUSIONS: Our data indicate that 30 mg of aspirin daily is no less effective in the prevention of vascular events than a 283-mg dose in patients with a transient ischemic attack or minor stroke, and has fewer adverse effects. PMID- 1922221 TI - Allogeneic bone marrow transplantation in multiple myeloma. European Group for Bone Marrow Transplantation. AB - BACKGROUND AND METHODS: In contrast to autologous bone marrow transplants for hematologic cancers, allogeneic transplants contain no tumor cells that might cause a relapse. We report the results of such allogeneic bone marrow transplantation using HLA-compatible sibling donors in 90 patients with multiple myeloma performed in 26 European centers between 1983 and 1989. RESULTS: At the time of the most recent follow-up, 79 months after the start of the study, 47 patients were alive and 43 were dead. The rate of complete remission after bone marrow transplantation was 43 percent for all patients and 58 percent for the patients who had engraftment. The actuarial survival at 76 months was 40 percent. The median duration of relapse-free survival among patients who were in complete remission after bone marrow transplantation was 48 months. The stage of the disease at diagnosis and the number of treatment regimens tried before bone marrow transplantation were predictive of the likelihood of complete remission after engraftment. There were trends toward longer survival among patients who were responsive to treatment before bone marrow transplantation, patients with Stage I disease at diagnosis, and patients who had received only first-line treatment before transplantation, as compared with those who were not responsive, those with Stage II or III disease at diagnosis, and those who had received three or more lines of treatment, but the differences in these factors were not statistically significant. Two post-transplantation factors predicted better long term survival: complete remission after engraftment and grade I graft-versus-host disease, rather than grade II, III, or IV. CONCLUSIONS: Allogeneic bone marrow transplantation with the use of HLA-matched sibling donors appears to be a promising method of treatment for some patients with multiple myeloma. PMID- 1922222 TI - Effects of pancreas transplantation on postprandial glucose metabolism. AB - BACKGROUND: Because a pancreas allograft is placed in the pelvis, pancreas transplantation abolishes the normal gradient between portal-vein and peripheral vein insulin concentrations and causes systemic hyperinsulinemia. Whether pancreas transplantation restores carbohydrate metabolism to normal is not known. METHODS: We studied seven patients with insulin-dependent diabetes mellitus after pancreas-kidney transplantation, seven nondiabetic patients after kidney transplantation (to control for immunosuppression), and eight normal subjects. Measurements were made after an overnight fast and after ingestion of a mixed meal. RESULTS: Although plasma glucose concentrations did not differ in the two transplant groups, plasma insulin concentrations were significantly higher in the diabetic pancreas-kidney recipients than in the nondiabetic kidney recipients, both before the meal (mean +/- SE, 102 +/- 15 vs. 53 +/- 6 pmol per liter; P less than 0.05) and afterward (123 +/- 22 vs. 61 +/- 6 nmol per liter per six hours; P less than 0.05). Plasma C-peptide concentrations were the same in both groups, indicating that hyperinsulinemia was due to decreased insulin clearance rather than increased insulin secretion. Despite drainage of the venous effluent from the transplanted pancreas into the systemic circulation, the values for splanchnic clearance of ingested glucose, suppression of hepatic glucose release, incorporation of carbon dioxide into glucose, stimulation of glucose oxidation, glucose uptake, and forearm glucose clearance were all similar in the transplant groups and differed minimally from the values in the normal group. The similar rates of glucose uptake in the presence of higher systemic insulin concentrations indicated that the extrahepatic tissues of the diabetic pancreas-kidney recipients were insulin-resistant. CONCLUSIONS: Despite systemic delivery of insulin, pancreas-kidney transplantation in patients with diabetes results in carbohydrate metabolism similar to that in nondiabetic subjects receiving the same immunosuppressive agents after kidney transplantation. PMID- 1922223 TI - Prevention of high-altitude pulmonary edema by nifedipine. AB - BACKGROUND: Exaggerated pulmonary-artery pressure due to hypoxic vasoconstriction is considered an important pathogenetic factor in high-altitude pulmonary edema. We previously found that nifedipine lowered pulmonary-artery pressure and improved exercise performance, gas exchange, and the radiographic manifestations of disease in patients with high-altitude pulmonary edema. We therefore hypothesized that the prophylactic administration of nifedipine would prevent its recurrence. METHODS: Twenty-one mountaineers (1 woman and 20 men) with a history of radiographically documented high-altitude pulmonary edema were randomly assigned to receive either 20 mg of a slow-release preparation of nifedipine (n = 10) or placebo (n = 11) every 8 hours while ascending rapidly (within 22 hours) from a low altitude to 4559 m and during the following three days at this altitude. Both the subjects and the investigators were blinded to the assigned treatment. The diagnosis of pulmonary edema was based on chest radiography. Pulmonary-artery pressure was measured by Doppler echocardiography and the difference between alveolar and arterial oxygen pressure was measured in simultaneously sampled arterial blood and end-expiratory air. RESULTS: Seven of the 11 subjects who received placebo but only 1 of the 10 subjects who received nifedipine had pulmonary edema at 4559 m (P = 0.01). As compared with the subjects who received placebo, those who received nifedipine had a significantly lower mean (+/- SD) systolic pulmonary-artery pressure (41 +/- 8 vs. 53 +/- 16 mm Hg, P = 0.01), alveolar-arterial pressure gradient (6.6 +/- 3.8 vs. 11.8 +/- 4.4 mm Hg, P less than 0.001), and symptom score of acute mountain sickness (2.0 +/- 0.7 vs. 3.9 +/- 1.9, P less than 0.01) at 4559 m. CONCLUSIONS: The prophylactic administration of nifedipine is effective in lowering pulmonary-artery pressure and preventing high-altitude pulmonary edema in susceptible subjects. These findings support the concept that high pulmonary-artery pressure has an important role in the development of high-altitude pulmonary edema. PMID- 1922224 TI - When physicians treat members of their own families. Practices in a community hospital. AB - BACKGROUND: Little is known about the circumstances under which physicians care for family members. We sought to examine current practice and, in particular, to learn how often family members request medical care or treatment, whether physicians accede to such requests, and what concerns, if any, physicians have about caring for their family members. METHODS: In late 1990 we distributed a pretested, structured questionnaire to all members of the active medical staff (physicians with M.D. or D.O. degrees) of a large suburban community teaching hospital. Of 691 eligible members of the medical staff, 465 physicians responded. RESULTS: Of the 465 respondents, 461 (99 percent) reported requests from family members for medical advice, diagnosis, or treatment. A total of 386 (83 percent of the respondents) had prescribed medication for a family member, 372 (80 percent) had diagnosed medical illnesses, 334 (72 percent) had performed physical examinations, 68 (15 percent) had acted as a family member's primary attending physician in the hospital, and 44 (9 percent) had operated on a family member. In addition, 152 (33 percent) reported that they had observed another physician "inappropriately involved" in a family member's care, and 103 (22 percent) had acceded to a specific request about which they felt uncomfortable. CONCLUSIONS: Practicing physicians often attend and treat their family members and diagnose their illnesses. They may often experience some disquiet in doing so. For physicians, complete medical data, proper training, and sound judgment are essential when family members request treatment. PMID- 1922225 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 44-1991. A 17-year-old Cambodian girl with recurrent abdominal pain and a tender mass in the right lower quadrant. PMID- 1922226 TI - Aspirin, the ageless remedy? PMID- 1922227 TI - Toward a cure for multiple myeloma? PMID- 1922228 TI - When lungs on mountains leak. Studying pulmonary edema at high altitudes. PMID- 1922229 TI - Physicians' aid in dying. PMID- 1922230 TI - Zidovudine and the natural history of AIDS. PMID- 1922231 TI - Pneumocystis carinii pneumonia in adults without predisposing illnesses. PMID- 1922232 TI - Fluconazole and Candida krusei fungemia. PMID- 1922233 TI - Administrative efficiency of the U.S. health care system. PMID- 1922234 TI - Second neoplasms after acute lymphoblastic leukemia in childhood. AB - BACKGROUND: Effective forms of treatment for acute lymphoblastic leukemia (ALL) in childhood now result in survival rates above 70 percent at five years, but the treatments are potentially carcinogenic. To determine the magnitude of this risk and identify possible risk factors for the development of second neoplasms, we studied a large cohort of children treated for ALL. METHODS AND RESULTS. We undertook a retrospective cohort study of 9720 children who had been given a diagnosis of ALL between June 1972 and August 1988 and had been treated according to the therapeutic protocols of the Children's Cancer Study Group. The median follow-up was 4.7 years (range, 2 months to 16 years). We found that 43 second neoplasms occurred among the children in the cohort, including 24 neoplasms of the central nervous system, 10 new leukemias and lymphomas, and 9 other neoplasms. This represented a 7-fold excess of all cancers and a 22-fold excess of neoplasms of the central nervous system. The estimated cumulative proportion of children in whom a second neoplasm developed was 2.53 percent 15 years after diagnosis (95 percent confidence limits, 1.74 percent and 3.38 percent). An even higher risk, particularly of central nervous system tumors, was evident in children five years of age or less at the time of the diagnosis of ALL (P = 0.012). All central nervous system neoplasms developed in children who had previously undergone irradiation. There was no association with exposure to cyclophosphamide or anthracyclines. CONCLUSIONS: There is a substantial excess of second neoplasms, especially of the central nervous system, among children treated for ALL. Children five years old or younger and those receiving radiation are at higher risk, especially for second tumors arising in the central nervous system. PMID- 1922235 TI - A comparison of single-dose cefixime with ceftriaxone as treatment for uncomplicated gonorrhea. The Gonorrhea Treatment Study Group. AB - BACKGROUND: Because of the widespread existence of Neisseria gonorrhoeae resistant to penicillin or tetracycline, ceftriaxone is now recommended for the treatment of gonorrhea. There is, however, a need for effective antibiotics that can be administered orally as an alternative to ceftriaxone, which requires intramuscular administration. Cefixime is an orally absorbed cephalosporin that is active against resistant gonococci and has pharmacokinetic activity suitable for single-dose administration. METHODS AND RESULTS: In a randomized, unblinded multicenter study of 209 men and 124 women with uncomplicated gonorrhea, we compared three single-dose treatment regimens: 400 mg or 800 mg of cefixime, administered orally, and 250 mg of ceftriaxone administered intramuscularly. The overall cure rates were 96 percent for the 400-mg dose of cefixime (89 of 93 patients) (95 percent confidence interval, 93.5 percent to 97.8 percent); 98 percent for the 800-mg dose of cefixime (86 of 88 patients) (95 percent confidence interval, 94.6 percent to 100 percent); and 98 percent for ceftriaxone (92 of 94 patients) (95 percent confidence interval, 94.9 to 100 percent). The cure rates were similar in men and women, and pharyngeal infection was eradicated in 20 of 22 patients (91 percent). Thirty-nine percent of 303 pretreatment gonococcal isolates had one or more types of antimicrobial resistance; the efficacy of all three regimens was independent of the resistance pattern. Chlamydia trachomatis infection persisted in at least half the patients infected in each treatment group. All three regimens were well tolerated. CONCLUSIONS: In the treatment of uncomplicated gonorrhea, a single dose of cefixime (400 or 800 mg) given orally appears to be as effective as the currently recommended regimen of ceftriaxone (250 mg given intramuscularly). PMID- 1922236 TI - Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association. AB - BACKGROUND: Chemotherapy for metastatic breast cancer is palliative, and the optimal duration of therapy is unknown. We designed a trial to determine whether continuous treatment is superior to stopping treatment after a brief induction period and resuming treatment when the disease progresses. METHODS: We treated 250 women with metastatic breast cancer with six courses of cyclophosphamide, doxorubicin, and fluorouracil given every three weeks. At the completion of this induction period, women whose disease either regressed or remained stable were randomly assigned to receive either continued treatment with cyclophosphamide, methotrexate, and fluorouracil (maintenance therapy) or no further treatment (observation) followed by treatment with cyclophosphamide, methotrexate, and fluorouracil when disease progression became evident (reinduction). RESULTS: The combined rate of complete and partial responses after initial therapy was 30 percent (71 of 233 patients who could be evaluated; 95 percent confidence interval, 25 percent to 37 percent). In another 42 percent (98 patients), the disease remained stable. A total of 145 patients were randomized. Seventy-one were randomly assigned to the maintenance-therapy group, and 74 to the observation group. The median time to progression was 9.4 months for patients in the maintenance-therapy group and 3.2 months for patients in the observation group (P less than 0.001). After reinduction therapy, the median time to progression was 3.5 months. The median length of survival from the time of initial therapy was 14.8 months for all 250 patients; it was 21.1 months for the 71 patients in the maintenance-therapy group and 19.6 months for the 74 patients in the observation group (P = 0.67). Maintenance therapy was the most important determinant of the time before progression (P less than 0.001), but it was not associated with prolonged survival. The changes in performance status were similar in the patients in both groups, but nausea, vomiting, and mucositis were significantly more frequent in the maintenance-therapy group. CONCLUSIONS: In patients with breast cancer who received induction chemotherapy for 18 weeks, subsequent continuous chemotherapy was associated with a significant prolongation of the time before progression as compared with those receiving no further therapy; overall survival, however, was not significantly different in the two groups. PMID- 1922237 TI - Bone marrow transplantation for sickle cell disease. A study of parents' decisions. AB - BACKGROUND: Bone marrow transplantation has been shown to cure sickle cell disease, but it carries a 15 percent mortality risk. To determine whether parents would accept this risk to cure their children of sickle cell disease, we interviewed parents of children with sickle cell disease who were being followed in a university hospital clinic. METHODS: We assessed parents' attitudes by using questions based on the standard reference-gamble paradigm. After we gave them descriptions of bone marrow transplantation and graft-versus-host disease (GVHD), the parents were presented with a series of hypothetical situations. In the first situation, bone marrow transplantation was described as offering certain (100 percent) survival with cure of sickle cell disease. In subsequent descriptions, the mortality rate associated with bone marrow transplantation was increased by 5 percent increments. The parents indicated the highest mortality risk at which they would consent to the procedure in order to cure their children. RESULTS: In order to obtain a cure for their children, 36 of 67 parents (54 percent) were willing to accept some risk of short-term mortality, 25 of 67 (37 percent) were willing to accept at least the 15 percent short-term mortality risk we estimate to be the current figure for bone marrow transplantation, and 8 of 67 (12 percent) were willing to accept a short-term mortality risk of 50 percent or more. Nine parents (13 percent) said they would accept both a mortality risk of 15 percent or more and an additional 15 percent risk of GVHD. The parents' decisions were not related to the clinical severity of their children's illness. CONCLUSIONS: At current rates of mortality and morbidity with bone marrow transplantation, a substantial minority of the parents of children with sickle cell disease may consent to bone marrow transplantation for their children. Parental attitudes should be factored into decisions about whether to offer bone marrow transplantation to children with sickle cell disease. PMID- 1922238 TI - Gaucher's disease. PMID- 1922239 TI - Sexually transmitted diseases in the 1990s. PMID- 1922240 TI - Metastatic breast cancer. Length and quality of life. PMID- 1922241 TI - Home monitoring of uterine activity. Does it prevent prematurity? PMID- 1922242 TI - Home monitoring for uterine activity. A response from the FDA. PMID- 1922243 TI - Home monitoring of uterine activity. A response from Tokos Medical Corporation. PMID- 1922244 TI - Genetic basis of familial amyotrophic lateral sclerosis. PMID- 1922245 TI - The role of reperfusion-induced injury in the pathogenesis of the Crush syndrome. PMID- 1922246 TI - Case 22-1991: portal-vein thrombosis. PMID- 1922247 TI - Potential for bias in economic analyses. PMID- 1922248 TI - JetSki pressure sores. PMID- 1922249 TI - Unsuccessful emergency medical resuscitation--are continued efforts in the emergency department justified? AB - BACKGROUND: The majority of attempts to resuscitate victims of prehospital cardiopulmonary arrest are unsuccessful, and patients are frequently transported to the emergency department for further resuscitation efforts. We evaluated the efficacy and costs of continued hospital resuscitation for patients in whom resuscitation efforts outside the hospital have failed. METHODS: We reviewed the records of 185 patients presenting to our emergency department after an initially unsuccessful, but ongoing, resuscitation for a prehospital arrest (cardiac, respiratory, or both) by an emergency medical team. Prehospital and hospital characteristics of treatment for the arrest were identified, and the patients' outcomes in the emergency room were ascertained. The hospital course and the hospital costs for the patients who were revived were determined. RESULTS: Over a 19-month period, only 16 of the 185 patients (9 percent) were successfully resuscitated in the emergency department and admitted to the hospital. A shorter duration of prehospital resuscitation was the only characteristic of the resuscitation associated with an improved outcome in the emergency department. No patient survived until hospital discharge, and all but one were comatose throughout hospitalization. The mean stay in the hospital was 12.6 days (range, 1 to 132), with an average of 2.3 days (range, 1 to 11) in an intensive care unit. The total hospital cost for the 16 patients admitted was $180,908 (range per patient, $1,984 to $95,144). CONCLUSIONS: In general, continued resuscitation efforts in the emergency department for victims of cardiopulmonary arrest in whom prehospital resuscitation has failed are not worthwhile, and they consume precious institutional and economic resources without gain. PMID- 1922250 TI - Calcium supplementation to prevent hypertensive disorders of pregnancy. AB - BACKGROUND: Calcium supplementation has been reported to reduce blood pressure in pregnant and nonpregnant women. We undertook this prospective study to determine the effect of calcium supplementation on the incidence of hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) and to determine the value of urinary calcium levels as a predictor of the response. METHODS: We studied 1194 nulliparous women who were in the 20th week of gestation at the beginning of the study. The women were randomly assigned to receive 2 g per day of elemental calcium in the form of calcium carbonate (593 women) or placebo (601 women). Urinary excretion of calcium and creatinine was measured before calcium supplementation was begun. The women were followed to the end of their pregnancies, and the incidence of hypertensive disorders of pregnancy was determined. RESULTS: The rates of hypertensive disorders of pregnancy were lower in the calcium group than in the placebo group (9.8 percent vs. 14.8 percent; odds ratio, 0.63; 95 percent confidence interval, 0.44 to 0.90). The risk of these disorders was lower at all times during gestation, particularly after the 28th week of gestation (P = 0.01 by life-table analysis), in the calcium group than in the placebo group, and the risk of both gestational hypertension and preeclampsia was also lower in the calcium group. Among the women who had low ratios of urinary calcium to urinary creatinine (less than or equal to 0.62 mmol per millimole) during the 20th week of gestation, those in the calcium group had a lower risk of hypertensive disorders of pregnancy (odds ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09) and less of an increase in diastolic and systolic blood pressure than the placebo group. The pattern of response was similar among the women who had a high ratio of urinary calcium to urinary creatinine during the 20th week of gestation, but the differences were smaller. CONCLUSIONS: Pregnant women who receive calcium supplementation after the 20th week of pregnancy have a reduced risk of hypertensive disorders of pregnancy. PMID- 1922251 TI - A look-back investigation of patients of an HIV-infected physician. Public health implications. AB - BACKGROUND: Transmission of the human immunodeficiency virus (HIV) to five patients receiving care from an HIV-infected dentist in Florida has recently been reported. Current data indicate that the risk of HIV transmission from health care workers to patients is low. Despite this low risk, programs to notify patients of past exposure to an HIV-infected health care worker are being conducted with increasing frequency. METHODS: We recently conducted an investigation of all the patients cared for by an HIV-infected family physician during a period when he had severe dermatitis caused by Mycobacterium marinum on his hands and forearms. After reviewing the patients' records, we notified 336 patients who had undergone one or more procedures (digital examination of a body cavity or vaginal delivery) placing them at potentially increased risk of HIV infection. The patients were offered tests for HIV infection and counseling. RESULTS: Of the 336 patients, 325 (97 percent) had negative tests for HIV antibody, 3 (1 percent) refused testing, 1 (less than 1 percent) died of a cause unrelated to HIV infection before notification, and the HIV-antibody status of 7 (2 percent) remained unknown. The direct and indirect public health costs of this investigation were approximately $130,000. CONCLUSIONS: The results of this investigation raise important questions about the risk of HIV transmission from health care workers to patients and the usefulness of HIV look-back programs, particularly in the light of recently published recommendations from the Centers for Disease Control. We propose that before a look-back investigation is undertaken, there should be a clearly identifiable risk of transmission of the infection, substantially higher than the risk requiring limitation of an HIV infected health care worker's practice prospectively. PMID- 1922252 TI - Racial differences in the cause-specific prevalence of blindness in east Baltimore. AB - BACKGROUND: Bilateral blindness unrelated to simple refractive error is twice as prevalent among blacks as among whites, although the difference narrows among the elderly. The reasons for this race- and age-related pattern are uncertain. METHODS AND RESULTS: A randomly selected, stratified, multistage cluster sample of 2395 blacks and 2913 whites 40 years of age and older in East Baltimore underwent detailed ophthalmic examinations by a single team. We identified 64 subjects who were blind in both eyes. The leading causes of blindness were unoperated senile cataract (accounting for blindness in 27 of the total of 128 eyes), primary open-angle glaucoma (17 eyes), and age-related macular degeneration (16 eyes). Together, these three disorders accounted for 47 percent of all blindness in this sample. Unoperated cataract accounted for 27 percent of all blindness among blacks, among whom it was four times more common than among whites; whites were almost 50 percent more likely than blacks to have undergone cataract extraction before the age of 80 (P less than 0.002). Primary open-angle glaucoma accounted for 19 percent of all blindness among blacks; it was six times as frequent among blacks as among whites and began 10 years earlier, on average. By contrast, age-related macular degeneration resulting in blindness was limited to whites, among whom it was the leading cause of blindness (prevalence, 2.7 per 1000; 95 percent confidence interval, 1.2 to 5.4); it affected 3 percent of all white subjects 80 years of age or older. CONCLUSIONS: The pattern of blindness in urban Baltimore appears to be different among blacks and whites. Whites are far more likely to have age-related macular degeneration, and blacks to have primary open-angle glaucoma. The high rate of unoperated cataracts among younger blacks and among elderly subjects of both races suggests that health services are underused. Half of all blindness in this urban population is probably preventable or reversible. PMID- 1922253 TI - Undertreatment of glaucoma among black Americans. AB - BACKGROUND: Cross-sectional studies and those using national data sets estimate that glaucoma-related blindness is between six and eight times more common among black Americans than among whites. Community-based studies have found that glaucoma is four to six times more prevalent among blacks. It is not known why blacks with glaucoma are more likely to become blind than whites with glaucoma. METHODS: To investigate the possibility that undertreatment of glaucoma is an important factor contributing to this higher rate of blindness, we studied the population-based rates of incisional and laser surgery for open-angle glaucoma among blacks and whites in a 5 percent random sample of Medicare claims for 1986 through 1988. RESULTS: For all U.S. census divisions combined, the rate of surgery for glaucoma among black Medicare beneficiaries was 2.2 times higher than the rate among white beneficiaries (95 percent confidence interval, 2.1 to 2.3). We calculated an expected rate of treatment among blacks on the basis of the rate of treatment among whites and the assumption that glaucoma is four times more prevalent among blacks--a conservative estimate. The observed rate of glaucoma surgery among blacks was 45 percent lower than the expected rate we calculated, which may in part account for the excess rate of blindness among blacks. The magnitude of this difference in treatment rates varied from 29 percent in the Middle Atlantic states to 50 percent in the South Atlantic states. CONCLUSIONS: Older black Americans are not receiving potentially sight-saving care for open angle glaucoma at the same rate as older white Americans. PMID- 1922254 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 46-1991. A 64-year-old man with recurrent hemoptysis, a bronchoesophageal fistula, and broncholithiasis. PMID- 1922255 TI - Resuscitation outside the hospital--what's lacking? PMID- 1922256 TI - Pregnancy, preeclampsia, and the endothelial cell. PMID- 1922257 TI - The differential burden of blindness in the United States. PMID- 1922258 TI - Indexes predictive of weaning from mechanical ventilation. PMID- 1922259 TI - Initial treatment of patients with extensive trauma. PMID- 1922260 TI - Circulating candida enolase in invasive candidiasis. PMID- 1922261 TI - The causative agent of bacillary angiomatosis. PMID- 1922262 TI - Parasitic infections in troops returning from Operation Desert Storm. PMID- 1922263 TI - Musculoskeletal pain in renal-transplant recipients. PMID- 1922264 TI - Rhinofacial zygomycosis caused by Conidiobolus coronatus. A case report. AB - A case of rhinofacial zygomycosis with of years duration, caused by Conidiobolus coronatus is described. The patient, a 72-years-old woman, presented with a bilateral distortion of the subcutaneous tissue and disfigurement of the face. Treatment with ketoconazole and potassium iodide did not prevent several relapses. At present she is still under treatment with fluconazole with clinical healing. Histopathological and mycological examination confirmed the dermatological diagnosis. An increasing number of cases of zygomycosis caused by fungi of the order Entomophthorales have also been reported in the Northern and Northeastern States of Brazil. PMID- 1922265 TI - Histoplasmosis in individuals with acquired immunodeficiency syndrome (AIDS): report of six cases with cutaneous-mucosal involvement. AB - The authors report the first six cases of disseminated histoplasmosis and acquired immunodeficiency syndrome (AIDS) seen at the University Hospital, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, from 1987 to 1989, with emphasis on dermatological clinical manifestations, nasal mucosa lesions and treatment. The mycosis was the first manifestation of AIDS in four patients. It is concluded that biopsies of the lesions for histopathologic study and fungal culture are important for diagnosis. PMID- 1922266 TI - In vitro antagonism of bioluminescent fungi by Trichoderma harzianum. AB - Two species of bioluminescent fungi, Panellus stypticus and Omphalotus olearius were placed in contact with three different strains of interfungal pathogenic Trichoderma harzianum. Subsequent light emission by the luminous fungi and advance of the interfungal pathogens were compared. Relative differences among the pathogens were reflected in their rate of mycelial advance, the total area over which they produced spores upon the host fungi, and decreases in host bioluminescence. After ten days differences in the total surface areas of spore production varied from 1 to 53 per cent. Differences in the reduction of bioluminescence of the same material ranged over 2 orders of magnitude. Final reduction in luminescence ranged over 6 orders of magnitude. A marked reduction in bioluminescence was observed to precede the advance of spore production. The greatest reduction in luminescence was correlated with the presence of T. harzianum hyphae. Two strains of T. harzianum, NRRL 1698 and ATCC 58674, were effective against both bioluminescent fungi within the study period while a third strain, NRRL 13019, was only effective against Omphalotus olearius. PMID- 1922267 TI - Effect of parboiling and bran removal on aflatoxin levels in Sri Lankan rice. AB - Commercial parboiling of rice in Sri Lanka and many south Asian countries provides ideal conditions for the occurrence of aflatoxins because the rice is steeped (allowing fermentation) thus providing ideal conditions for growth of toxigenic Aspergillus species. However the traditional 'cottage' method of parboiling rice, which does not involve steeping, appears to reduce Aspergillus growth even after long storage periods. Preferential infection of parboiled rice by Aspergillus flavus was observed. Aflatoxin contents in inoculated rice produced by commercial parboiling (AFB1 60-92 mg/kg) were significantly higher than that in inoculated 'cottage' processed rice (AFB1 12-29 micrograms/kg). The steeping (precooking/soaking) process in commercial parboiling appears to increase the susceptibility of rice grains to fungal infection. Aflatoxin content in grains increased considerably with the increase in duration of soaking. However, the addition of 10 ppm calcium hypochlorite (bleach) to soaking water appreciably reduced A. flavus contamination and subsequent aflatoxin content in parboiled rice. No significant reduction in aflatoxin levels were observed after bran removal of contaminated rice. PMID- 1922268 TI - Differential cytotoxicity and mycotoxin content among isolates of Fusarium moniliforme. AB - Ten different isolates of the common corn fungus, Fusarium moniliforme, were cultured on corn, and the production by the isolates of two important mycotoxins, fusarin C and fumonisin B1, was compared. Additionally, both aqueous and organic extracts of the cultures were tested for cytotoxicity to rat primary hepatocytes by measuring the effects of three dose levels on the ability of the cells to take up valine and to cause the release of the cytoplasmic enzyme, lactate dehydrogenase. The fungal isolates differed drastically in their ability to produce the two mycotoxins and in their cytotoxicity. However the toxic effects could not be accounted for by the content of the two toxins measured. Therefore it appears that there are other toxins, both organic and aqueous soluble compounds, that are toxic to liver cells. PMID- 1922269 TI - An evaluation of straw-extract agar media for the growth and sporulation of Madurella mycetomatis. AB - Four new media, namely Wheat straw extract agar, Bajra straw extract agar, Jowar straw extract agar and Paddy straw extract agar, were evaluated for their potential to stimulate the growth and sporulation of Madurella mycetomatis in comparison with the conventional Sabouraud dextrose agar and Soil extract agar. Vegetative growth of M. mycetomatis on the four types of Straw extract agars was superior to that obtained on Sabouraud dextrose agar. Isolates of M. mycetomatis sporulated better and faster on the Straw extract agars than on the Sabouraud dextrose agar and Soil extract agar. Straw extract agar is recommended as a sporulation medium for M. mycetomatis. It may prove useful especially for studies of the conidium ontogeny of the fungus for elucidating its taxonomic status. PMID- 1922270 TI - Effect of gamma irradiation and water activity on mycotoxin production of Alternaria in tomato paste and juice. AB - Gamma-irradiation, water activity (aw) and incubation temperature were found to affect the production of tenuazonic acid (TZA) by Alternaria alternata in tomato paste and juice. By increasing the irradiation doses, the dry weight as well as TZA decreased greatly until complete inhibition at 4 kGy. Greatest production of TZA occurred at 0.98 aw (57.5 micrograms/g and 26.3 micrograms/g) for both tomato paste and juice, respectively, at 25 degrees C. Changing temperature and aw altered the relative amounts of TZA produced in tomato paste und juice by unirradiated and irradiated conidia of A. alternata. Only trace amount of TZA was detected at 0.98 aw (1.50 micrograms/g) by 3 kGy-irradiated conidia in tomato paste, while it was inhibited completely in juice. Increasing gamma-irradiation doses and decreasing water activities decreased greatly or inhibited TZA production in both tomato paste and juice. PMID- 1922271 TI - Metal content in certain food products. AB - The aim of the researches was the determination of the lead, cadmium, iron, copper and zinc content in selected food products available in everyday life in the city of Cracow. It was found that all food products contain lead and cadmium contaminations. The trace element content in the Polish food products was within the range of values obtained by other authors. PMID- 1922272 TI - Antimutagenic activity of lettuce and chard extracts. AB - The ability of lettuce and chard extracts to reduce the mutagenic activity of Benzo[a]pyrene was studied. In this experiment several groups of male Balb/C mice were treated with different doses of the substances under study. B[a]p was administered at doses of 36 and 72 mg/kg of body weight to groups II and III, respectively. The lettuce extract combined with the doses of B[a]p were administered to groups IV and V. The experiment was performed again under the same conditions to test the effect of chard extract. Urine samples were tested by means of the Ames assay. The results show that the mutagenic activity of the urine samples from groups treated with B[a]p was reduced when the treatment also included any vegetable extract. PMID- 1922273 TI - Modern immunoassays in meat-product analysis. AB - The increased regulation of foodstuffs in modern society requires analytical methods which are easy to perform, sensitive, specific and relatively inexpensive. The basic antigen-antibody reaction provides means for very specific analytical procedures. Immunoassays are powerful analytical tools that permit the specific and rapid detection or measurement of antigens and haptens to which antibodies can be produced. Sensitive recognition of the interaction is made possible by labelling the analyte or antibody, mainly with radioisotope (RIA) and enzyme (ELISA). Wide applications of these modern immunoassays to food analysis began about 1980. The paper reviews investigations, where various types of RIA and ELISA were developed for the use in meat product analysis. Detection and determination of various meat species, non-meat proteins, microorganisms and bacterial toxins, drugs, anabolic hormones, pesticides, mycotoxins, and other contaminants in meat and meat products by the means of immunoassays is described. Now, the commercial kits are available for most of these compounds. They make possible to perform analysis in different laboratories under standard conditions. The reason of an enthusiasmic acceptance of this technology is related to its inherent specificity, high sensitivity, and the facility of application. In fact, immunoassays compete with other analytical technics. They have the advantage of economy when screening large numbers of samples. PMID- 1922274 TI - [The degradation of vicine and convicine in field bean meal by selected bacterial strains]. AB - Vicine and convicine as natural occurring toxic compounds in Vicia faba are involved in the formation of hemolytic anemia (favism). Removal of these compounds needs high technological expense. Microbiological degradation with different strains of bacteria was tried. After 3 h incubation with Streptococcus faeciens convicine was converted completely and Vicine to about 95%. PMID- 1922275 TI - [Toxicological effect of a fatty acid mixture in rats]. AB - The effects of a fatty acids mixture containing nearly 50% odd numbered fatty acids (PC-Saure) were studied in a subchronic toxicity test in male and female rats. The animals received PC-Saure in their diet at levels of 0, 1.25, 2.5 and 5% for 13 weeks. Food intake was increased at 5% PC-Saure level in males. Food efficiency was initially decreased in males and females of this group. Ingestion of PC-Saure resulted in increases of the urine volume and the urinary lactate dehydrogenase activity in both sexes. Male and female rats fed PC-Saure showed elevated serum activities of alkaline phosphatase and leucine aminopeptidase and decreases in serum cholesterol and triglycerides. Dietary PC-Saure elevated the serum creatinine content in males at the two highest levels. A transitory increase in the activity of the serum alanine aminotransferase was observed in females fed 5% PC-Saure. Increased liver and kidney weights were found in both sexes. PMID- 1922276 TI - [Mass spectrometric structure analysis of fatty acid mixtures from biological material after gas capillary chromatographical separation]. AB - The identification of mixtures of fatty acids from biological materials is possible by electron impact ionization mass spectra of methyl esters after their capillary gas chromatographic separation. Mass spectra of pyrrolidine derivatives are used for the determination of double bond positions in unsaturated fatty acids. 97 different fatty acids (saturated, unsaturated, branched, cyclic, hydroxy, oxo, epoxy and methoxy) and other compounds (alkanes, halogens, phthalates, ketones, aldehydes) were identified in yeast and bacterial biomasses, lipid-containing animal tissues and human sera as well as fish and plant oils (77 preparations). PMID- 1922277 TI - Influence of intestinal resection and type of diet on the digestive and metabolic utilization of fats in rats. AB - The effects of the quality of dietary fat, and the influence of ursodeoxycholic acid, an exogenous bile acid, on the digestive and metabolic utilization of fat were studied in rats in which 50% of the distal small intestine was resected. The fat content of the diets was quantitatively equivalent (4%), and differed only in the type of fat: olive oil (diet A) or 1/3 medium chain triglycerides (MCT), 1/3 sunflower oil and 1/3 olive oil (diet B). The removal of 50% of the distal small intestine led to a highly significant decline in the digestive utilization of fat (ADC) in animals given diet A. Rats fed diet B showed an increase in ADC to values approaching those seen in control animals. The addition of ursodeoxycholic acid to diet B failed to cause a further rise in the ADC of fat. After intestinal resection, serum levels of triglycerides and cholesterol fell more markedly in animals given diet A than in the diet B group, while the addition of ursodeoxycholic acid to diet B led to no further change. Serum lipid levels showed no significant influence of intestinal resection, but did accurately reflect the differences in fat composition between the two types of diet tested. PMID- 1922278 TI - [Toxicological evaluation of saccharose carbonic acid esters in basic subchronic feeding trials with rats. 1. Effect of saccharose fatty acid polyester]. AB - Groups of male and female rats received a sucrose fatty acid polyesters containing product (SPE) in their diet for 13 weeks at levels of 0, 5, 10 or 15%. Additional groups were pair-fed to the high-dose SPE-group (standard diet, 92.5%) or given food containing 7.5% hydrogenated lard (HF) or 4.5% fatty acid ethyl ester (FEE). Compared to the controls, there were increases in the food intake in males and females of the SPE-groups, HF- group and FEE-group. Male rats fed SPE showed increases in serum urea nitrogen at all levels, in serum alkaline phosphatase activity and urinary glucose excretion at 10 and 15%, in serum leucine amino-peptidase at 15%. In females dietary SPE increased the blood glucose content and serum alkaline phosphatase activity at 15% and the serum leucine aminopeptidase activity at 10 and 15%. PMID- 1922279 TI - Plasma butyrylcholinesterase activity in rats fed diets containing fish proteins. PMID- 1922280 TI - Adaptation of protein synthesis to protein diets in rats. PMID- 1922281 TI - Plasma and liver free amino acids in rats fed glycine supplemented casein diets. PMID- 1922282 TI - Improving drug abuse treatment. Overview of treatment issues. PMID- 1922283 TI - Improving drug abuse treatment. PMID- 1922284 TI - Client issues in drug abuse treatment: addressing multiple drug abuse. AB - Multiple drug abuse may involve the whole range of abused drugs, but the most critical problems exist with cocaine, alcohol, opioids, and benzodiazepines. The medical and psychosocial consequences of abusing these drugs in various combinations are often more severe than abusing each drug alone, and specific combinations of treatment options may be needed for many of these drugs. These combination treatments may include relapse prevention psychotherapies targeted toward drug-related cues that are specific to each type of drug as well as pharmacotherapies targeted toward specific drugs of abuse, such as naltrexone for opioid abuse and disulfiram for alcohol abuse. Few controlled clinical trials are available with multiple drug abusers, but successful treatments using pharmacological adjuncts such as disulfiram and amantadine have been described with cocaine-abusing or alcoholic methadone-maintained patients. PMID- 1922285 TI - Addressing psychiatric comorbidity. AB - Research studies indicate that addressing psychiatric comorbidity can improve treatment for selected groups of substance-abusing patients. However, the chances for implementing the necessary techniques on a large scale are compromised by the absence of professional input and guidance within programs. This is especially true in public programs, which treat some of the most disadvantaged, disturbed, and socially destructive individuals in the entire mental health system. One starting point for upgrading the level of knowledge and training of staff members who work in this large treatment system could be to develop a better and more authoritative information dissemination network. Such a system exists in medicine; physicians are expected to read appropriate journals and to guide their treatment decisions using the data contained in the journals. Standards of practice and methods for modifying current practice are within the tradition of reading new facts, studying old ones, and comparing treatment outcome under different conditions with what is actually being done. No such general system of information-gathering or -sharing exists, particularly in public treatment programs. One of the most flagrant examples of this "educational shortfall" can be found among those methadone programs that adamantly insist on prescribing no more than 30 to 35 mg/day for all patients, in spite of the overwhelming evidence that these dose levels generally are inadequate. In some cases, program directors are unaware of studies that have shown the relationship between dose and outcome. In other cases, they are aware of the studies but do not modify their practices accordingly. This example of inadequate dosing is offered as an example of one situation that could be improved by adherence to a system of authoritative and systematic information dissemination. Many issues in substance abuse treatment do not lend themselves to information dissemination as readily as that of methadone dosing. However, the existence of a general information/education system about substance abuse treatment, combined with adherence to it among care providers, not only would provide helpful data for treatment staff but also might stimulate their curiosity and initiative. These later qualities, along with additions to existing treatment resources, may in the long run serve as the best guarantee for improvement. and maintenance of quality care. PMID- 1922286 TI - Are there minimum conditions necessary for methadone maintenance to reduce intravenous drug use and AIDS risk behaviors? AB - Although methadone maintenance is a treatment modality with the demonstrated ability to reduce IV drug use and subsequent AIDS risk, methadone maintenance programs vary widely in their effectiveness: Demographically similar patient samples show profound improvements in some programs and little change in others. This suggests that programmatic factors rather than patient variables or sheer availability of methadone may be important active ingredients in effective methadone maintenance. The AIDS epidemic has led to the demand for increased availability of methadone, with suggested elimination of counseling, urine contingencies, and other rehabilitative services in an effort to fund additional "methadone-only" treatment slots. The data reviewed here, including preliminary results from a study examining the effectiveness of "minimal" methadone services, suggest that merely increasing the availability of methadone in the absence of administrative counseling, and rehabilitative services may not adequately protect the majority of patients from continued drug use and the risk of AIDS. PMID- 1922287 TI - Reducing illicit drug use among methadone patients. PMID- 1922288 TI - Improving client compliance in outpatient treatment: counselor-targeted interventions. AB - Earlier research has demonstrated the need for more effective strategies to increase treatment compliance, particularly in drug-free treatment programs. This need is particularly acute given the increased admissions of patients who use multiple drugs. Most efforts in this area have utilized client-targeted interventions to increase participation levels and length of retention. Thus, based on the studies cited in this chapter, counselor-targeted interventions may offer a cost-effective and potent alternative or adjunct to client-targeted interventions that should be the focus of future research. PMID- 1922289 TI - Retention in drug-free therapeutic communities. PMID- 1922290 TI - Using methadone effectively: achieving goals by application of laboratory, clinical, and evaluation research and by development of innovative programs. PMID- 1922291 TI - Using psychotherapy effectively in drug abuse treatment. PMID- 1922292 TI - Relapse prevention. AB - Although knowledge about relapse prevention is still at an early stage, the extant data highlight the importance of several constructs. 1. Motivation for abstinence remains central. The construct itself is often clouded because of its association with mystical notions such as willpower and self-control. We know that manipulation of environmental events can increase motivation. These interventions are effective, however, only as long as the contingencies are in effect. We need to develop and evaluate strategies for transferring contingency management to the natural environment, that is, to institutions and groups that can perpetuate them for the long term. Also, clarification of the kinds of abstinence goals needed to prevent relapse is important. 2. Coping skills have been studied by several investigators, but research on these, except for job finding skills, is not encouraging. The skills usually taught may be too basic. Skills training oriented to complex targets, such as building nondrug-using networks, may be useful and should be further explored. 3. Social support is clearly important, yet we do not know how best to use it to promote abstinence. The little research available suggests that both familial and nonfamilial systems should be mobilized. We need to define abstinence-promoting supportive behaviors, identify and engage important support systems in treatment, and help patients expand their nondrug-using contacts. 4. Negative affect may be causally related to relapse. We need to continue efforts to identify dysphoric patients and develop interventions to ameliorate dysphoria concurrent with drug abuse treatment (cf. Zweben and Smith 1989). 5. Drug cue reactivity and extinction to drug cues have been demonstrated in the laboratory. What is needed in this promising line of research are (1) investigation of cues and cue-reactivity phenomena in the natural environment or in conditions closely mimicking that environment and (2) extinction methods that transfer from the treatment setting to the outside world. Other phenomena are not well understood but seem intuitively important. Maladaptive ways of responding to lapses, such as the AVE, are included here. Another is stress, which our patients and our clinical intuition tell us must play a role in relapse. Its exact role is far from clear. PMID- 1922293 TI - Conditioning factors may help to understand and prevent relapse in patients who are recovering from drug dependence. PMID- 1922294 TI - Some special considerations for treatment of drug abuse and dependence in women. PMID- 1922295 TI - Opportunities for enhancing drug abuse treatment with criminal justice authority. PMID- 1922296 TI - Contemporary issues in drug abuse treatment linkage with self-help groups. PMID- 1922297 TI - Establishing a methadone quality assurance system: rationale and objectives. PMID- 1922298 TI - Methadone maintenance and patients in alcoholism treatment. PMID- 1922299 TI - Improving drug abuse treatment: recommendations for research and practice. PMID- 1922300 TI - Treatment outcomes for drug abuse clients. PMID- 1922301 TI - Defining the intervention and the target population. PMID- 1922302 TI - Implementation issues in drug abuse prevention research. AB - This chapter reviews methodological issues in evaluating the quality of implementation of drug abuse prevention programs. Issues of definition (adherence, exposure, reinvention), measurement (self-report, other's report, behavioral observation), and parameters of influence (person, situation, environment) are addressed. Implementation results of recent drug prevention and health promotion studies are reviewed as they relate to these issues. A general model is then proposed that represents implementation as a multiply determined process involving the interaction of person, situation, and environmental influences. Using this model, several recommendations are offered for estimating the "true" drug abuse prevention program effect as the average of effect estimates generated from experimental program assignment and level of program implementation. Potential differences between researcher and programmer standards of quality or level of implementation are noted, using the common interpretation of the efficacy/effectiveness research trial continuum as an example. PMID- 1922303 TI - Experimental and quasi-experimental designs in prevention research. PMID- 1922304 TI - Modeling of intervention effects. PMID- 1922305 TI - Outcome measurement issues in drug abuse prevention studies. PMID- 1922306 TI - Assessing effectiveness of drug abuse prevention: implementation issues relevant to long-term effects and replication. PMID- 1922307 TI - Subject attrition in prevention research. AB - Subject attrition threatens the internal validity of substance abuse prevention studies because differences in the rate of attrition and the substance use behavior of remaining subjects in the different conditions could account for any differences found in substance use rates. Attrition threatens the external validity of prevention studies because, to the extent that study dropouts are different from remaining subjects, the results of the study may not be generalizable to study dropouts. Analysis of these threats to the validity of prevention studies should be routinely conducted. However, studies of alcohol and drug abuse prevention have generally failed to report or analyze subject attrition. Smoking prevention studies have more frequently reported attrition, and they have recently begun to analyze the degree to which attrition may affect the internal and external validity of the study. Evidence thus far suggests that differences in attrition across conditions do occur occasionally. The evidence is substantial that study dropouts are systematically more likely to smoke, to use other substances, and to score highly on other risk-taking measures. PMID- 1922308 TI - Increasing the validity of self-report data in effectiveness trials. PMID- 1922309 TI - Technology transfer. PMID- 1922310 TI - Prevention evaluation research methods: findings and consensus. PMID- 1922311 TI - Prevention intervention research: challenges and opportunities. PMID- 1922312 TI - Contributions of drug epidemiology to the field of drug abuse prevention. PMID- 1922313 TI - A framework for drug abuse prevention research. PMID- 1922314 TI - Methodological issues in drug use prevention research: theoretical foundations. PMID- 1922315 TI - Joseph Lister and antisepsis in midwifery. PMID- 1922316 TI - AIDS and the divorced person. PMID- 1922317 TI - "Bridging the communication gap between traditional healers and nurses". PMID- 1922318 TI - Intravenous fluids. PMID- 1922319 TI - Wound care update--the basics. PMID- 1922320 TI - Science or sangoma? PMID- 1922321 TI - An infection control inservice workshop. PMID- 1922322 TI - [Trauma registers: a necessity for South Africa]. PMID- 1922323 TI - Lessons from the Alexandra Health Centre and University Clinic. PMID- 1922325 TI - AIDS insurance cover still available. PMID- 1922324 TI - AIDS help-line. PMID- 1922326 TI - On the maximum size of the AIDS epidemic among the heterosexual black population in South Africa. PMID- 1922327 TI - Helping the child with leukaemia attain his full potential. PMID- 1922328 TI - National Institutes of Health. Culture clash inside the walls. PMID- 1922329 TI - Risk assessment. End of an era. PMID- 1922330 TI - Biotechnology. Another major deal. PMID- 1922331 TI - AIDS research turned upside down. PMID- 1922332 TI - Antigen processing. Proteasomes in the pathway. PMID- 1922333 TI - Ribosomes. Drugs and the RNA world. PMID- 1922334 TI - Reproductive biology. A clue to Kartagener's. PMID- 1922335 TI - Muller's ratchet and flu virus. PMID- 1922336 TI - Sexual semantics. PMID- 1922337 TI - The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. AB - X-ray crystallography reveals electron density in the antigen-binding site of HLA B27 that is an interpretable image of nonameric peptides in a largely extended conformation. Clear density exists for the main chain and several side chains and is consistent with the sequence of 11 nonameric self-peptides eluted from HLA B27. Pockets in the antigen-binding cleft bind four side chains and the amino and carboxyl termini of the peptide. PMID- 1922338 TI - Identification of self peptides bound to purified HLA-B27. AB - A pool of endogenous peptides bound to the human class I MHC molecule, HLA-B27, has been isolated. Microsequence analysis of the pool and of 11 HPLC-purified peptides provides information on the binding specificity of the HLA-B27 molecule. The peptides all seem to be nonamers, seven of which match to protein sequences in a database search. These self peptides derive from abundant cytosolic or nuclear proteins, such as histone, ribosomal proteins, and members of the 90K heat-shock protein family. PMID- 1922339 TI - A cell autonomous function of Brachyury in T/T embryonic stem cell chimaeras. AB - Developmental genetics has shown that the Brachyury (T) gene has a key role in mesoderm formation during gastrulation in the mouse. Homozygous embryos have a defective allantois, degenerate or absent notochord and disrupted primitive streak and node. The neural tube is kinked and somite formation interrupted. The T gene has been cloned and is expressed during the early stages of gastrulation, being restricted to the primitive streak region, nascent mesoderm and notochord. Neither the sequence of the gene nor its expression pattern define its developmental function. To study the cell autonomy of the T mutation we have isolated and genetically characterized embryonic stem cell lines and studied their behaviour in chimaeras. T/+ embryonic stem cells form normal chimaeras, whereas T/T in equilibrium with +/+ chimaeras mimic the T/T mutant phenotype. The results indicate that the T gene acts cell autonomously in the primitive streak and notochord but may activate a signalling pathway involved in the specification of other mesodermal tissues. PMID- 1922340 TI - Sequence similarity between the mammalian bmi-1 proto-oncogene and the Drosophila regulatory genes Psc and Su(z)2. AB - The bmi-1 proto-oncogene can be activated by Moloney murine leukaemia proviral insertions in E mu-myc transgenic mice. It encodes a highly conserved nuclear protein of 324 amino acids which belongs to a family of proteins containing a putative new zinc-finger. Another closely related member of this family is the mouse protein Mel-18. Here we report on the cloning and characterization of a homologous gene (D-bmi) from Drosophila melanogaster. Our analysis indicates that distinct domains of the mouse Bmi-1 protein, including the putative zinc-finger motif, are highly conserved within the much larger D-Bmi protein. Chromosomal localization and sequence comparison reveal that D-bmi is identical to Posterior Sex Combs (Psc) and indicate that the conserved domains between mouse bmi and Psc are also conserved within Suppressor-2 of Zeste (Su(z)2). PMID- 1922341 TI - Structural and serological similarity of MHC-linked LMP and proteasome (multicatalytic proteinase) complexes. AB - Major histocompatibility complex (MHC) class I molecules associate with peptides derived from endogenously synthesized antigens. Cytotoxic T-lymphocytes can thus scan class I molecules and bound peptide on the surface of cells for foreign antigenic determinants. Recent evidence demonstrates that the products of trans acting, non-class I genes in the class II region of the MHC are required in the class I antigen-processing pathway. There are genes (called HAM1 and HAM2 in the mouse) in this region that encode proteins postulated to be involved in the transport of peptide fragments into the endoplasmic reticulum for association with newly synthesized class I molecules. But, the mechanism by which such peptide fragments are produced remains a mystery. At least two genes encoding subunits of the low-molecular mass polypeptide (LMP) complex are tightly linked to the HAM1 and HAM2 genes. We show that the LMP complex is closely related to the proteasome (multicatalytic proteinase complex), an intracellular protein complex that has multiple proteolytic activities. We speculate that the LMP complex may have a role in MHC class I antigen processing, and therefore that the MHC contains a cluster of genes required for distinct functions in the antigen processing pathway. PMID- 1922342 TI - A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC. AB - It is now possible to paint a detailed picture of how cytoplasmic proteins are handled by the immune system. They are apparently degraded in the cytoplasm into peptides. These are then transported into the endoplasmic reticulum where they encounter class I major histocompatibility complex (MHC) molecules. Once loaded with peptide, the HLA molecules move through the Golgi apparatus to the cell membrane. Until recently, it had not been established how peptides without signal sequences cross the ER membrane. However, a number of papers have now described a pair of membrane transporter genes of the ABC (ATP-binding cassette) super-family which are attractive candidates for this function. Both transporter genes, which may encode two halves of a heterodimer, are situated in the class II region of the MHC. There is evidence that other putative components of the processing machinery, the LMPs (low molecular mass polypeptides), are also encoded in the MHC. Similarities between the properties of the LMPs and a large intracellular protease complex, called proteasome, have led to the suggestion that LMPs are involved in processing antigens. We have now identified a human gene with sequence homology to proteasome components. Remarkably, this gene maps between the two putative peptide transporter genes. PMID- 1922343 TI - Antibiotic inhibition of group I ribozyme function. AB - The discovery of catalytically active RNA has provided the basis for the evolutionary concept of an RNA world. It has been proposed that during evolution the functions of ancient catalytic RNA were modulated by low molecular weight effectors, related to antibiotics, present in the primordial soup. Antibiotics and RNA may have coevolved in the formation of the modern ribosome. Here we report that a set of aminoglycoside antibiotics, which are known to interact with the decoding region of the 16S ribosomal RNA of Escherichia coli, inhibit the second step of splicing of the T4 phage-derived td intron. Thus catalytic RNA seems to interact not only with a mononucleotide and an amino acid, but also with another class of biomolecules, the sugars. Splicing of other group I introns but not group II introns was inhibited. The similarity in affinity and specificity of these antibiotics for group I introns and rRNAs may result from recognition of evolutionarily conserved structures. PMID- 1922345 TI - Homeopaths' cushion. PMID- 1922344 TI - Baltimore's defence. PMID- 1922346 TI - Biotechnology. French drug industry initiative. PMID- 1922347 TI - Nobel prize. Patch clamp brings honour. PMID- 1922348 TI - Research commercialization--SBIR is good business. PMID- 1922349 TI - Biotechnology. Yellow light on L-tryptophan. PMID- 1922350 TI - Biomedical research. Rockefeller loses one. PMID- 1922351 TI - Hong Kong. Science university debuts. PMID- 1922352 TI - Penicillin and beyond. AB - The discovery of penicillin remains one of the greatest advances in medical science. From the success of the discovery the biotechnology industry became established. PMID- 1922354 TI - Unspoken fears. PMID- 1922353 TI - Baltimore's unanswered questions. PMID- 1922355 TI - Multiple sclerosis. The case of the wonky mouse. PMID- 1922356 TI - Working bloody miracles. PMID- 1922358 TI - Where next for canine virus? PMID- 1922357 TI - Actin in ribbons. PMID- 1922359 TI - Break for SCIDs. PMID- 1922360 TI - TFIIS and strand-transfer proteins. PMID- 1922361 TI - A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules. AB - Kallmann's syndrome (clinically characterized by hypogonadotropic hypogonadism and inability to smell) is caused by a defect in the migration of olfactory neurons, and neurons producing hypothalamic gonadotropin-releasing hormone. A gene has now been isolated from the critical region on Xp22.3 to which the syndrome locus has been assigned: this gene escapes X inactivation, has a homologue on the Y chromosome, and shows an unusual pattern of conservation across species. The predicted protein has significant similarities with proteins involved in neural cell adhesion and axonal pathfinding, as well as with protein kinases and phosphatases, which suggests that this gene could have a specific role in neuronal migration. PMID- 1922362 TI - The int-2 proto-oncogene is responsible for induction of the inner ear. AB - The int-2 proto-oncogene encodes several products related to the fibroblast growth factor (FGF) family. FGFs have been associated with mesoderm induction in the amphibian embryo and int-2 has a distinct pattern of expression throughout development in vertebrates. But evidence for a function of int-2 in embryo genesis has been lacking. In the mouse embryo, int-2 transcripts have been detected in the rhombencephalon at a developmental stage where classical experiments showed that the induction of the inner ear occurs. This raises the possibility that int-2 may constitute a signal for the induction of the otic vesicle, the primordium of the inner ear. We provide direct evidence for this view by showing that (1) the formation of the otic vesicle is inhibited by antisense oligonucleotides targeted to the secreted form of int-2, and by antibodies against int-2 oncoproteins, and (2) basic FGF (bFGF) can mimic the inductive signal in the absence of the rhombencephalon. PMID- 1922363 TI - Concentration-dependent transcriptional activation or repression by Kruppel from a single binding site. AB - One of the gap class of segmentation genes, Kruppel (Kr), is required for normal thorax and abdominal development of the Drosophila embryo. Its gene product, a zinc-finger type protein, forms a bell-shape concentration gradient in a central position of the blastoderm. Genetic and molecular studies suggested that the Kr protein (KR) may act both as a positive and as a negative regulator of transcription on several other genes of the zygotic segmentation hierarchy. We have examined the regulatory potential of Kr by a series of cotransfection experiments in the Drosophila Schneider cell line system. Different doses of Kr expression plasmid were tested for their ability to drive reporter gene expression mediated by a single 11-base pair KR in vitro binding site common to several putative Kr target genes. Our results show that low amounts of Kr expression plasmid lead to transcriptional activation, whereas high amounts result in repression. Distinct portions of KR other than the DNA-binding domain are required for gene activation and repression, suggesting that KR itself can act as a concentration-dependent positive and negative regulator of transcription. PMID- 1922364 TI - Binding of general transcription factor TFIIB to an acidic activating region. AB - A central issue in eukaryotic transcriptional regulation is the mechanism by which promoter-specific transcription factors (activators) stimulate transcription. Two lines of evidence indicate that the general transcription factor TFIIB is a pivotal component in the mechanism by which an acidic activator functions. First, during assembly of the preinitiation complex TFIIB binding is a rate-limiting step enhanced by an acidic activator. Second, the TFIIB activity in a HeLa cell nuclear extract is specifically retained on a column containing an acidic activating region. But because our previous study monitored only TFIIB activity, it remains possible that the interaction between TFIIB and the acidic activating region is mediated through additional proteins, for example, those designated as adaptors, coactivators or mediators. A complementary clone encoding TFIIB has recently been isolated and shown to encode a polypeptide of relative molecular mass 35,000. Here we report that TFIIB expressed in and purified from Escherichia coli (recombinant TFIIB) binds directly to the potent acidic activating region of the herpes simplex virus-1 VP16 protein. PMID- 1922365 TI - A new human HLA class II-related locus, DM. AB - HLA class II molecules have a crucial role in the immune response to antigens. We have isolated two new class II-like complementary DNA sequences, RING6 and RING7, which map between the HLA-DNA and -DOB loci. They are novel members of the immunoglobulin gene family which may have diverged before the duplications that gave rise to the main class II loci. The RING6 and RING7 genes seem to encode alpha- and beta-chains of a previously undiscovered class II-related protein. PMID- 1922366 TI - New class II-like genes in the murine MHC. AB - Major histocompatibility complex (MHC) class I molecules present endogenous antigens to CD8+ (cytotoxic) T cells. MHC class II molecules present primarily exogenously derived antigens to CD4+ T cells. Three new genes (Ma, Mb1 and Mb2) located between the Pb and Ob genes of the murine MHC have properties indicating that they are members of the MHC class II gene family, but they are the most divergent class II members so far identified and are almost as closely related in sequence to class I genes as they are to the known class II genes. PMID- 1922367 TI - Mobile reactive centre of serpins and the control of thrombosis. AB - Two protease inhibitors in human plasma play a key part in the control of thrombosis: antithrombin inhibits coagulation and the plasminogen activator inhibitor PAI-1 inhibits fibrinolysis, the dissolving of clots. Both inhibitors are members of the serpin family and both exist in the plasma in latent or inactive forms. We show here that the reactive centre of the serpins can adopt varying conformations and that mobility of the reactive centre is necessary for the function of antithrombin and its binding and activation by heparin; the identification of a new locked conformation explains the latent inactive state of PAI-1. This ability to vary conformation not only allows the modulation of inhibitory activity but also protects the circulating inhibitor against proteolytic attack. Together these findings explain the retention by the serpins of a large and unconstrained reactive centre as compared to the small fixed peptide loop of other families of serine protease inhibitors. PMID- 1922368 TI - Crystal structure of an RNA double helix incorporating a track of non-Watson Crick base pairs. AB - The crystal structure of the RNA dodecamer duplex (r-GGACUUCGGUCC)2 has been determined. The dodecamers stack end-to-end in the crystal, simulating infinite A form helices with only a break in the phosphodiester chain. These infinite helices are held together in the crystal by hydrogen bonding between ribose hydroxyl groups and a variety of donors and acceptors. The four noncomplementary nucleotides in the middle of the sequence did not form an internal loop, but rather a highly regular double-helix incorporating the non-Watson-Crick base pairs, G.U and U.C. This is the first direct observation of a U.C (or T.C) base pair in a crystal structure. The U.C pairs each form only a single base-base hydrogen bond, but are stabilized by a water molecule which bridges between the ring nitrogens and by four waters in the major groove which link the bases and phosphates. The lack of distortion introduced in the double helix by the U.C mismatch may explain its low efficiency of repair in DNA. The G.U wobble pair is also stabilized by a minor-groove water which bridges between the unpaired guanine amino and the ribose hydroxyl of the uracil. This structure emphasizes the importance of specific hydrogen bonding between not only the nucleotide bases, but also the ribose hydroxyls, phosphate oxygens and tightly bound waters in stabilization of the intramolecular and intermolecular structures of double helical RNA. PMID- 1922370 TI - How affordable is public health? PMID- 1922369 TI - Mutation detection. AB - The detection and characterization of mutations in genes has become a major area of interest in many areas of biology. Such variation may account for speciation, tumour formation, drug resistance, as well as the more obvious nature of inherited disease. PMID- 1922371 TI - Aquarium fights back. PMID- 1922372 TI - Challenge to AZT. PMID- 1922373 TI - Europe approves first transgenic animal patent. PMID- 1922374 TI - Green light for ddI. PMID- 1922375 TI - Integrity review halted. PMID- 1922376 TI - Approvals still slow, but pipeline full. PMID- 1922377 TI - Cracks in the RAC. PMID- 1922378 TI - India. Saving female babies. PMID- 1922379 TI - Genome ethics. PMID- 1922380 TI - Wittgenstein. PMID- 1922381 TI - Tests for rodent polyphyly. PMID- 1922382 TI - Retinal receptors in rodents maximally sensitive to ultraviolet light. AB - High sensitivity to near-ultraviolet light is a fundamental feature of vision in many invertebrates. Among vertebrates there are some amphibians, birds and fishes that are also sensitive to near-ultraviolet wavelengths. This sensitivity can be achieved through a class of cone photoreceptor containing an ultraviolet sensitive pigment. Although these receptors were thought not to exist in the eyes of mammals, we now report that some rodents have a retinal mechanism that is maximally sensitive to ultraviolet light. PMID- 1922383 TI - Cloned neuronal IK(A) channels reopen during recovery from inactivation. AB - The kinetic behaviour and functional role of potassium ion (K+) channels mediating a fast-inactivating K+ current (IK(A)) has been widely discussed. Activating in the subthreshold range of excitation, IK(A) channels are assumed to reduce the excitatory effect of depolarizing membrane currents in a time dependent manner. Here we report that IK(A) channels not only open in response to a depolarization but open again after repolarization of the membrane. Although the current in response to the depolarization is rapidly inactivating, the current elicited by repolarization declines slowly and produces long-lasting afterhyperpolarizations under current-clamp conditions. This implies an additional physiological role for IK(A) channels, particularly those that activate positive to the threshold of excitation. The underlying biophysical mechanism was studied by fast-application of peptides corresponding to the N terminal end of the IK(A) channel proteins. It was found to be a voltage dependent release of the inactivation gate. PMID- 1922384 TI - Subunit of the '20S' proteasome (multicatalytic proteinase) encoded by the major histocompatibility complex. AB - Cytotoxic T lymphocytes recognize fragments (peptides) of protein antigens presented by major histocompatibility complex (MHC) class I molecules. In general, the peptides are derived from cytosolic proteins and are then transported to the endoplasmic reticulum where they assemble with the MHC class I heavy chains and beta 2-microglobulin to form stable and functional class I molecules. The proteases involved in the generation of these peptides are unknown. One candidate is the proteasome, a nonlysosomal proteinase complex abundantly present in the cytosol. Proteasomes have several proteolytically active sites and are complexes of high relative molecular mass (Mr about 600K), consisting of about 20-30 subunits with Mrs between 15 and 30K. Here we show that at least one of these subunits is encoded by the mouse MHC in the region between the K locus and the MHC class II region, and inducible by interferon-gamma. This raises the intriguing possibility that the MHC encodes not only the MHC class I molecules themselves but also proteases involved in the formation of MHC-binding peptides. PMID- 1922385 TI - Second proteasome-related gene in the human MHC class II region. AB - Antgen processing involves the generation of peptides from cytosolic proteins and their transport into the endoplasmic reticulum where they associate with major histocompatibility complex (MHC) class I molecules. Two genes have been identified in the MHC class II region, RING4 and RING11 in humans, which are believed to encode the peptide transport proteins. Attention is now focused on how the transporters are provided with peptides. The proteasome, a large complex of subunits with multiple proteolytic activities, is a candidate for this function. Recently we reported a proteasome-related sequence, RING10, mapping between the transporter genes. Here we describe a second human proteasome-like gene, RING12, immediately centromeric of the RING4 locus. Therefore RING12, 4, 10 and 11 form a tightly linked cluster of interferon-inducible genes within the MHC with an essential role in antigen processing. PMID- 1922386 TI - Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1. AB - Professional phagocytes, such as neutrophils and monocytes, have an NADPH oxidase that generates superoxide and other reduced oxygen species important in killing microorganisms. Several components of the oxidase complex have been identified as targets of genetic defects causing chronic granulomatous disease. The complex consists of an electron transport chain that has as its substrate cytosolic NADPH and which discharges superoxide into the cavity of the intracellular phagocytic vacuole. The only electron transport component identified so far is a low potential cytochrome b, apparently the only membrane component required. At least three cytosolic factors are also necessary, two of which, p67phOx and p47phOx, have been identified by their absence in patients with chronic granulomatous disease. A third component, sigma 1, is required for stimulation of oxidase activity in a cell-free system. The active components of purified sigma 1 are two proteins that associate as heterodimers, and here we report that these are the small GTP-binding protein p21rac1 and the GDP-dissociation inhibitor rhoGDI. PMID- 1922387 TI - Phosphorylation of c-jun mediated by MAP kinases. AB - The proto-oncogene c-jun is a component of the AP-1 transcription factor family involved in the mediation of nuclear events elicited by extracellular stimuli. The c-jun protein is negatively regulated by phosphorylation of residues near the carboxy terminus which are dephosphorylated in response to phorbol esters. Here we identify two serine residues in the amino terminal A1 transactivation domain which are phosphorylated in response to a variety of mitogens, phorbol esters and activated ras. We present evidence that mitogen-activated protein-serine (MAP) kinases (pp54 and pp42/44) specifically phosphorylate these sites and that their phosphorylation positively regulates the transacting activity of c-jun. The MAP kinase enzymes pp54 and pp42/44 are regulated by tyrosine as well as serine/threonine phosphorylation. MAP kinase activation of c-jun may underlie the common stimulation of this transcription factor by mitogens, growth factors and oncogenes. PMID- 1922388 TI - Y-chromosome-specific DNA amplified in ancient human bone. PMID- 1922389 TI - On the development of alternative antiepileptic drugs. Lack of enantioselectivity of the anticonvulsant activity, in contrast to teratogenicity, of 2-n-propyl-4 pentenoic acid and 2-n-propyl-4-pentynoic acid, analogues of the anticonvulsant drug valproic acid. PMID- 1922390 TI - [The influence of consumer and direction on the quality of agricultural products and nutrition]. AB - The modern consumer is very much interested in healthy food. The reason is that a special group of consumers is focusing more and more attention on health and nutrition problems. Further, there is increased emphasis on education in food science at universities as well as polytechnics. For some years worldwide dietary goals are published with the intention to reduce nutrition-based sickness. For the first time in our nutrition report 1988, clear proposals for optimal nutrition were formulated. PMID- 1922391 TI - Intravenous drug use fools us again. The importance of open lung biopsy in evaluating a patient with progressive interstitial lung disease presenting with pneumothorax. PMID- 1922392 TI - Organ transplantation in North Carolina. A response to the Inspector General's Report. PMID- 1922394 TI - Infant mortality in North Carolina. PMID- 1922393 TI - The distribution of organs for transplantation. What is fair and practical? PMID- 1922395 TI - Men and chronic disease: reducing the risk through nutrition. PMID- 1922396 TI - Che Gelida Manina. Fentanyl intoxication. PMID- 1922397 TI - Futility: newer guidelines to endorse with caution. PMID- 1922398 TI - Chaos, alcoholism, and DWI. PMID- 1922399 TI - "It could not have been done better in Philadelphia, Paris, or anywhere else". The first fifty years of anesthesia in North Carolina (1846-1896). PMID- 1922400 TI - The "imperative of prevention". PMID- 1922401 TI - Statement to the physicians of North Carolina from the Committee on Drug Abuse and Pharmacy of the North Carolina Medical Society. PMID- 1922402 TI - Extracorporeal membrane oxygenation for newborn infants with persistent pulmonary hypertension. PMID- 1922403 TI - Extracorporeal membrane oxygenation treatment. One-year outcomes for North Carolina infants. AB - Initial survival rates for the first 45 North Carolina ECMO neonates in the study group are somewhat better than national figures. Developmental functioning as assessed at one year of age is comparable to that reported in other studies. A congenital diaphragmatic hernia diagnosis was significantly related to poorer outcome. Measures of family functioning approximate those reported for families of non-ECMO neonates treated in intensive care. Support provided by ECMO staff was rated at a notably high level. With nearly three thousand survivors and multiple numbers of ECMO centers now operating in this country, ECMO has made the transition from an experimental treatment to an established procedure for treatment of neonates in pulmonary failure. A few beginning attempts to utilize ECMO with older patients are being made. Neonatologists are now directing efforts toward refining techniques and selection criteria. Further evaluation of longer term effects of this type of treatment is essential. Effective protocols for follow-up care need to be designed, particularly for those at greatest risk for developmental disability. PMID- 1922404 TI - Out-of-hospital do not resuscitate orders in North Carolina. PMID- 1922405 TI - Good nutrition can make the difference for your children. AB - What children eat and how they are fed has a direct impact on their health and well being. While they are growing up, they are also learning how to eat. Parents are the most effective nutrition educators. Parents teach by what they eat, by what they buy and by what they offer to their children. Parents also teach about nutrition by their attitudes. Help your children learn that eating can be a delightful, tasty celebration of health. PMID- 1922406 TI - Alopecia areata. PMID- 1922407 TI - Nickel allergy. PMID- 1922408 TI - Medicine at Wake Forest University, 1941-1991. PMID- 1922409 TI - Neither shall they learn war any more. Health considerations for Desert Storm veterans. PMID- 1922410 TI - A new approach to military graduate medical education programs. PMID- 1922411 TI - Comment on Ewing's sarcoma article. PMID- 1922412 TI - Periactin for headaches? PMID- 1922413 TI - Treatment of anaphylaxis. PMID- 1922414 TI - Surveying requirements make paperwork a priority. PMID- 1922415 TI - Safe harbor regulations are official, but provide little room to anchor. AB - In summary, the safe harbor regulations, while welcome in certain instances, do not provide a great deal of comfort or assurance with regard to investments by referrers such as physicians, or in ventures between providers and potential referrers. Individuals in relationships not covered by the safe harbors should at least reexamine those relationships and evaluate the risk involved in continuing in the relationship. PMID- 1922416 TI - The NRAA: a look back, a look ahead. As political insight becomes more important in the renal care field, Association urge members to become more involved. National Renal Administrators Association. PMID- 1922417 TI - Safe harbor regulations: the law has not changed. PMID- 1922418 TI - OPO regulations lack backbone to eliminate inefficiency. Organ procurement organizations. PMID- 1922419 TI - Surgeon General holds workshop on organ donation. PMID- 1922420 TI - Using CQI to improve quality in the organ procurement organization. Continuous quality improvement. PMID- 1922421 TI - Why can't they be like we were? PMID- 1922422 TI - An interview with J. Jarrett Clinton. Interview by Carmella A. Bacchino. AB - Medical effectiveness initiatives, outcomes research, and practice guidelines- the new buzz words for the 90s--will change the way health care services are delivered and allocated. The focal point for medical effectiveness and health services research for the federal government is the Public Health Service's newest agency, the Agency for Health Care Policy and Research. The agency is headed by J. Jarrett Clinton, MD, MPH, administrator, who also served as acting administrator since the creation of the agency in December 1989 until April 1991. In this interview, Dr. Clinton discusses the agency's responsibilities, his perspective on the agency's work, and the effect of health services research on the U.S. health care delivery system. PMID- 1922423 TI - Redesigning hospitals around patients and technology. AB - Hospitals must drastically redesign themselves and revise their operations to be successful. Four major redesign initiatives will enable the traditional hospital to provide effective patient care while attaining its own profitability goals. PMID- 1922424 TI - Health care rationing: the Oregon experiment. AB - Oregon Medicaid reforms, passed by the state legislature in 1989, examined in light of Oregon's recent history of attempts to grapple continually rising health care costs. PMID- 1922425 TI - The nurse as professnocrat. AB - One of the greatest difficulties in being a nurse in the 1990s is maintaining excellent care in the face of economic constraints. This article explores how organizations (including hospitals), which originated as bureaucracies, need to change their format. Nurses can have great impact on organizations as they serve as "Professnocrats" who understand that professional goals and bureaucratic goals can be integrated in health care organizations of the future. PMID- 1922426 TI - Management training effects on nurse manager leadership behavior. AB - Costly organization-based leadership/management development training gives little evidence that such training affects long-term changes in nurse manager leader style adaptability in meeting situations and staff needs. PMID- 1922427 TI - The Iowa model: a proposed model for nursing administration. AB - The purpose of the Iowa Model is to serve both as a heuristic device and as a framework for articulating knowledge for nursing administration research, practice, and education. The model delineates two domains of knowledge (systems and outcomes), each with three levels (patient aggregates, the organization, and the health care system). Concepts useful for knowledge development are identified for each level. Practice, research, and curricular applications of the model are made. PMID- 1922428 TI - Changing the start of the hospital workweek. AB - Essential to the success of a project of this magnitude were: (a) having the support and input of both management and staff; (b) clarifying federal wage and hour issues; (c) allowing adequate time for the change process; (d) determining impact of change on every hospital department; (e) providing hospital departments with necessary information, resources, and support to accommodate the change; and (f) communicating the change to each hospital employee in a timely manner. Can a hospital provide budget-neutral, flexible nurse schedules necessary to recruit and retain registered nurses? Yes, they can if they know how to do it. By redefining the workweek, Saint Marys realized an annual decrease of almost $750,000 in scheduled overtime expense for full-time nurses working 12-hour weekends, every third weekend. If health care institutions want the competitive edge in recruiting nurses, they will need to provide work schedules that are not only attractive, but also help ensure a positive "bottom line." PMID- 1922429 TI - The demise of the golden era. AB - As Cohen states (1991, p. 25), "The future role that nursing will play in the health care delivery system is one of many major issues faced by contemporary nursing ... Nursing must be able to determine realistically the cost of and evaluate the effectiveness of nursing care provided to its patients." A unit based financial management committee is one very effective way of teaching the skills needed for the professional nurse to advance the practice in financial management. This will help nursing gain the professional status that they have always worked for. But beyond these very lofty ideals, a staff nurse managed financial management committee can make the nurse manager's life much easier. Staff nurses need to understand and accept the importance of managing the financial as well as the quality side of patient care. When this happens, the budget becomes theirs. Nurses develop a sense of ownership of the budget and learn how to effectively manage the unit's finances. Much staff nurse brain power is not used. Systems must be developed to access nurses' effective ideas for financial management--first in a financial management committee and then on the unit. Not only will this develop the professional status that nurses need and deserve, but it will also impact the cost of health care. In a society where the cost of an appendectomy requires Dayton Hudson to sell 39,000 Ninja Turtle action figures, Atlantic Richfield to sell 192,000 gallons of gas a day, Anheuser-Busch to sell 11,627 6-packs of 12 oz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922430 TI - Achieving lasting organizational improvements through employee involvement. PMID- 1922431 TI - Disagreements with 'impact of federalism' article. PMID- 1922433 TI - The safety of medical devices and the role of the FDA. PMID- 1922432 TI - Can health services research improve America's health care? PMID- 1922434 TI - Staff nurse financial management committees--the nurse manager's guide to effective financial performance. AB - As Cohen states (1991, p. 25), "The future role that nursing will play in the health care delivery system is one of many major issues faced by contemporary nursing... Nursing must be able to determine realistically the cost of and evaluate the effectiveness of nursing care provided to its patients." A unit based financial management committee is one very effective way of teaching the skills needed for the professional nurse to advance the practice in financial management. This will help nursing gain the professional status that they have always worked for. But beyond these very lofty ideals, a staff nurse managed financial management committee can make the nurse manager's life much easier. Staff nurses need to understand and accept the importance of managing the financial as well as the quality side of patient care. When this happens, the budget becomes theirs. Nurses develop a sense of ownership of the budget and learn how to effectively manage the unit's finances. Much staff nurse brain power is not used. Systems must be developed to access nurses' effective ideas for financial management--first in a financial management committee and then on the unit. Not only will this develop the professional status that nurses need and deserve, but it will also impact the cost of health care. In a society where the cost of an appendectomy requires Dayton Hudson to sell 39,000 Ninja Turtle action figures, Atlantic Richfield to sell 192,000 gallons of gas a day, Anheuser-Busch to sell 11,627 6-packs of 12 oz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922435 TI - Changing the way we do business. PMID- 1922436 TI - An interview with Rhonda Anderson. Interview by Connie R. Curran. AB - Nurse executives working in a hospital system experience varied and challenging opportunities to enhance the quality of patient care as well as the success of their professional careers. In this interview, Rhonda Anderson, MPA, RN, CNAA, discusses the hospital system, the managed care environment, and the importance of developing nurse managers. PMID- 1922437 TI - Financial responsibilities and preparation of chief nurse executives. AB - Chief nurse executives face staggering financial responsibility. Findings indicate a variety of processes are used to administer budgets in excess of $14 million. On-the-job experience, instead of formal education, is the major means of acquiring expertise in financial management. PMID- 1922438 TI - Entrepreneurial nursing as a conceptual basis for in-hospital nursing practice models. PMID- 1922439 TI - Dynamic shortages of registered nurses. PMID- 1922440 TI - Canadian nurses under a single-payer system: advantage or disadvantage? AB - The American nursing community has not wholeheartedly endorsed comprehensive health care system reform because of fear that nursing salaries, wage compression, direct reimbursement, and political power will be negatively affected in a single-payer system. These issues are evaluated under the Canadian health care system (a single-payer system). The source of payment does not appreciably affect these issues. PMID- 1922441 TI - When nurses terminate: the exit interview/questionnaire. AB - Reliable information on termination issues can enhance retention and recruitment efforts. Blank nursing exit questionnaire/interview forms from 49 hospitals were analyzed. A sample exit questionnaire and recommendations for the collection of data regarding the departing nurse are provided. PMID- 1922442 TI - A hard pill to swallow. PMID- 1922443 TI - Preventing slippage: assuring follow-up of abnormal test results. PMID- 1922444 TI - The debate over HIV testing/disclosure. PMID- 1922445 TI - Groupware for nurse managers. PMID- 1922446 TI - Facilitating a fast turnaround: the leadership challenge for a new nurse manager. PMID- 1922447 TI - Customized productivity feedback systems improve nursing performance and reduce costs. PMID- 1922448 TI - [Reduction in thyroid gland size due to radioactive iodine in patients with a large goiter]. PMID- 1922449 TI - [Radiation effects and protection standards]. PMID- 1922450 TI - [Radioactive iodine; a useful alternative in the treatment of non-toxic goiter?]. PMID- 1922451 TI - [Horner's syndrome: can we turn a blind eye?]. PMID- 1922452 TI - [Gender identity disorders in children]. PMID- 1922453 TI - [The relationship between predisposing factors in liver abscesses and the causative bacteria]. AB - In order to assess the correlation between bacteria isolated from liver abscesses and factors predisposing to liver abscesses, a retrospective study of clinical and bacteriological data on 21 patients with 27 episodes of pyogenic abscesses was carried out at the University Medical Centre, Amsterdam. Out of 27 episodes, 15 (55%) were associated with biliary or pancreatic disease; in seven of these 15 episodes more than one microorganism was cultured. Enterobacteriaceae were isolated in 13 (85%) of 15 episodes. Anaerobic bacteria were recovered only when operations in the pancreatico-biliary area had been performed previously. Seven episodes (26%) were related to extrahepatic disease; anaerobic bacteria (Bacteroides and Fusobacterium spp.) were isolated in five of these seven episodes. Streptococcus milleri seemed especially prominent, since this bacterium was cultured in six of seven episodes. Enterobacteriaceae were not involved in these seven episodes. Other factors predisposing to liver abscesses (15%) were diabetes mellitus n = 2), paraproteinaemia (n = I), and metastatic carcinoid (n = I). Blood cultures were positive in 65% of 23 episodes, but 40% of the positive cultures contained a smaller number of bacterial species than could be cultured from the abscess itself. Bacteria isolated from liver abscesses are related to the underlying predisposing condition. For diagnosis of the underlying condition and antibiotic therapy, puncture and bacteriologic examination of the abscess is essential. PMID- 1922454 TI - [Medium-long-term good results of vertical gastroplasty in the treatment of morbid obesity]. AB - To determine the long-term results of the surgical treatment of patients with morbid obesity, a retrospective analysis of the patients in whom a vertical banded gastroplasty according to Mason was performed in the period 1982-1990 was carried out in the department of General Surgery, St. Joseph Hospital, Veldhoven, the Netherlands. In a series of 20 patients (4 men and 16 women) with a mean age of 32 (17-53) years who were eligible for treatment according to international criteria surgery was performed. The preoperative weight averaged 124 (94-207) kg and the mean preoperative excess weight was 60 (37-132) kg. Immediate postoperative complications occurred in 5 and late complications in 7 patients. Revision for technical complications was necessary in 2 patients. Twelve patients were followed up for more than 4 years. The mean weight loss after 4 years was 37 (18-89) kg, which was 28 (18-43) per cent of the mean preoperative weight and 62 (31-89) per cent of the mean preoperative excess weight. The 4-year results were unsatisfactory (less than 50 percent excess weight loss) in 3 of the 12 patients. It is concluded that vertical banded gastroplasty in our hands seems a relatively safe and effective surgical method of achieving sustained weight loss in most patients. PMID- 1922455 TI - [Dieulafoy's exulceratio simplex, a life-threatening gastric hemorrhage]. AB - The 'exulceratio simplex Dieulafoy' is an uncommon and probably underdiagnosed cause of upper gastrointestinal haemorrhage. The bleeding is intermittent and even endoscopically often missed. In this article the pathogenesis, diagnostic methods, clinical presentation and therapy are discussed. We present one case treated in our hospital. PMID- 1922456 TI - [Epileptic insult developing immediately following administration of propofol]. AB - This article describes the occurrence of an epileptic insult immediately after the intravenous bolus administration of 200 mg propofol (Diprivan) in a healthy patient with no medical history of epilepsy or other neurological diseases. Extensive neurological examinations including EEG and CT scan did not reveal any abnormalities. We want to emphasise that even in the absence of neurological disorders propofol may induce an instantaneous epileptic insult. PMID- 1922457 TI - [Eurothemes. 'Everything was grey, drab and brown. Country's own youth can best introduce Western practicalities in Hungary']. PMID- 1922458 TI - [The request for an HIV-antigen test in clinical practice]. PMID- 1922459 TI - [Conversional or somatic?]. PMID- 1922460 TI - [Scientific research and privacy]. PMID- 1922461 TI - [A psychiatric disorder in an intensive care unit]. PMID- 1922462 TI - [The distribution of scarce resources in health care]. PMID- 1922463 TI - [Referral problems in patients with a symptomatic HIV infection]. PMID- 1922464 TI - [Historical perspective of donor anonymity in artificial insemination with donor sperm]. PMID- 1922465 TI - ['Do not resuscitate' policy]. PMID- 1922466 TI - [Policy in resuscitation orders; an addition to the CBO Report (Central Guidance Organ)]. PMID- 1922467 TI - [The effect of disease on metabolism; still a lot of misunderstanding]. PMID- 1922468 TI - [Energy and protein requirements in illness and trauma]. PMID- 1922469 TI - [Policy in no-resuscitation orders. Work Group of the Central Guidance Organ for Intercollegiate Testing CBO]. AB - Discussions on the inappropriateness of cardiopulmonary resuscitation have led to installation of a working committee by the scientific council of the National Organization for Quality Assurance in Hospitals. The report of this committee contains recommendations on the process by which the decision to write a Do-Not Resuscitate order can be reached. In the report some practical advice is given and the responsibilities of physicians are made clear. The patient's wish remains the central issue. PMID- 1922470 TI - [Diabetes mellitus as cause of death]. AB - Certification and coding of diabetes mellitus as a cause of death were investigated by sending a random sample of 300 physicians a set of 6 case histories. Of these, 228 (76%) participated in the study by completing a death certificate for each of these cases. The certificates were subsequently coded by the Central Bureau of Statistics. The main finding was that doctors varied enormously in the way in which diabetes mellitus was mentioned on the death certificate: not at all, as a contributory cause of death, or as an underlying cause of death. Coding removes some of the inconsistencies, but induces additional variation: a higher age of the deceased is associated with a lower probability of having diabetes mellitus coded as the underlying cause of death, and a higher probability of not receiving a code of diabetes mellitus at all. It is concluded that the cause-of-death registration does not provide an accurate picture of the contribution of diabetes mellitus to the cause-of-death pattern of the Netherlands. This is due, amongst other things, to the conceptualization of causes of death on which the registration is based. On the other hand, changes in certification and coding practice within the current system may already lead to some improvement. PMID- 1922471 TI - [Aspecific eye disorders in Lyme disease]. AB - Lyme disease shows a large variety of clinical signs and symptoms. Ocular disease may occur in the disseminated stage of the disease. Ocular signs are often not specific of Lyme disease. In the presence of unexplained ocular disease it may be wise to consider Lyme disease as a possible diagnosis. Diagnosis and therapy in two Lyme disease patients with ocular disease are discussed. PMID- 1922472 TI - [Various theoretical considerations on innovation of health care]. PMID- 1922473 TI - [Attitude of primiparae on the possibility of sex preselection]. PMID- 1922474 TI - [Pregnancy diabetes]. PMID- 1922475 TI - [Following the wrong policy]. PMID- 1922476 TI - [Reversible dementia syndromes]. PMID- 1922477 TI - ['Ballooning' in the year 1991]. PMID- 1922478 TI - [Diet and liver cirrhosis]. PMID- 1922479 TI - [Liver and physical exertion]. PMID- 1922480 TI - [The elderly patient with intermediate-grade and high-grade malignant non-Hodgkin lymphoma]. PMID- 1922481 TI - [Consensus food hypersensitivity]. AB - Approximately 500 allergists, dermatologists, ENT specialists, paediatricians, general practitioners, pulmonologists and dietitians attended a consensus meeting about food hypersensitivity in September 1990 in Utrecht. At this meeting the clinical manifestations, mechanisms, diagnosis and treatment were discussed. Consensus was reached about the use of terminology such as food allergy (defined as immunologically mediated), intolerance (non-immunological) and aversion (psychological). However consensus was not reached on all points; there was much discussion on the role of food allergy in atopic dermatitis. During the meeting the opinions of the different health care professionals appeared to concur. PMID- 1922482 TI - [Sexually transmissible disorders in allochtonous population groups; a pilot study]. AB - In the registration of sexually transmitted diseases (STD) carried out by the nursing staff in the STD clinics the share of the immigrant populations of Turkish, Moroccan, Surinam and Antilles origin was investigated for the period 1986-89. In the total population of STD patients the immigrants appear to be overrepresented. Their share has increased from one-eight to one-fifth of the total number of STD cases. The STD rates (number of cases per 1000) for the Turkish and Moroccan populations are high, even after adjusting for population size and age. High STD rates are most apparent among males, especially among Turkish males. In comparison with the Dutch population more gonorrhoea is found among immigrants, in particular penicillinase producing Neisseria gonorrhoeae (PPNG). Turkish males (and prostitutes) contributed much to this relatively high prevalence. Further research is to be initiated in order to obtain better insight into the occurrence of STD among immigrant populations in The Netherlands, especially in connection with a potentially increased risk of infection with Human Immunodeficiency Virus (HIV). PMID- 1922483 TI - [Consensus early treatment with zidovudine]. AB - The aim was to reach national consensus on the moment early treatment with the antiretroviral drug zidovudine should be started and on the dosing schedule to be used. On the initiative and under the auspices of the National AIDS Therapy Evaluation Centre a consensus meeting of Dutch AIDS treatment specialists was organised on March 6, 1991. A number of expert-speakers made recommendations on the basis of currently available information. These were amended in a plenary discussion. Subsequently the participants could comment upon a draft consensus document. Premises were that the starting point of treatment should be easily applicable and that the moment chosen should be neither too early nor too late in the course of HIV infection. The zidovudine dose had to be an effective one, and the dosing schedule user-friendly. The consensus was that zidovudine should be started in asymptomatic HIV-infected persons at a peripheral blood CD4+ cell count less than or equal to 0.3 x 10(9)/l. In the presence of additional laboratory indicators of a poor prognosis and in persons with early clinical symptoms of HIV infection, it was preferred to start treatment at a CD4+ cell count less than or equal to 0.4 x 10(9)/l. In view of the natural fluctuation in the number of CD4+ cells it was felt to be injudicious to act upon a single count. The recommended zidovudine dose is 200 mg 3 times daily. In case of serious toxicity the dose should be lowered to 100 mg 3 times daily, although for this dose no long-term efficacy data are available. PMID- 1922484 TI - [Multiple sclerosis in childhood]. AB - A 15-year-old girl presented with signs and symptoms indicative for multiple sclerosis. A final diagnosis could only be reached after 9 years follow up and with help of the MRI technique. The differential diagnosis of multiple sclerosis at a young age is discussed. PMID- 1922485 TI - [Exogenous modification of reproductive disorders; more questions than facts]. PMID- 1922486 TI - [Is there room for the non-surgical treatment of cholesterol gallstones?]. PMID- 1922487 TI - [Tacrine in the treatment of Alzheimer's disease]. PMID- 1922488 TI - [The treatment of axillary hyperhidrosis]. PMID- 1922489 TI - [Carboplatin in the treatment of ovarian carcinoma; as effective and less toxic in comparison with cisplatin]. AB - The efficacy and toxicity of a combination of carboplatin and cyclophosphamide (CC) were studied in a group of 76 patients with advanced ovarian cancer. Progression-free (PFS) and overall survival (OS) were compared with a historical group of 68 patients treated with cyclophosphamide, adriamycin and cisplatin (CAP 5). Subjective toxicity was compared by measurement of TWIST, the Time Without Symptoms of Treatment or Disease. Of 75 evaluable patients treated with CC, 18 (24%) had a pathologically complete remission (pCR), and 31 (41%) a partial remission (PR). CC led to grade 3 leukopenia in 38% and grade 4 in 3% of 421 treatment cycles. Thrombocytopenia grade 3 was seen after 7% and grade 4 after 2% of cycles. Treatment delay occurred in 11.5% and dose reduction in 21% of cycles. Nephro- or neurotoxicity did not occur. After a median followup of 18 months, the median PFS was greater than or equal to 22 and the OS was greater than or equal to 25 months. Median duration of TWIST was greater than or equal to 22 versus greater than or equal to 10 months after CAP-5 (p less than 0.01). Compared with historical controls, treatment with CC is equivalent to CAP-5. It is free of nephro- and neurotoxicity, but is more myelosuppressive. Quality of life, measured by TWIST, is significantly better during CC. Owing to its equivalent efficacy with lower subjective toxicity, carboplatin should replace cisplatin in treating patients with advanced ovarian cancer. PMID- 1922490 TI - [Euthanasia and assisted suicide by physicians in the home situation. I. Diagnoses, age and sex of patients]. AB - In order to map out morbidity, age and sex of patients with whom family doctors participated in euthanasia or assisted suicide, an exploratory, descriptive, retrospective study was carried out primarily regarding the period 1986-1989. Data were collected via an anonymous written injury among an at random sample of family doctors in North Holland (n = 521), and family doctors in the rest of the Netherlands (n = 521). In addition, police reports of euthanasia/assisted suicide administered by family doctors in North Holland (n = 263) were analysed. The inquiry included among others questions about the last case doctors had encountered. Diagnoses were classified according to the ICD-9. The results were compared with compiled mortality data relating to persons who died in their own homes. Correlations and differences were analysed by means of the chi2-test. The response to the inquiry was 67% (non-responders did not otherwise differ from responders): 228 (North Holland), 160 (rest of the Netherlands) and 263 (police reports) cases could be analysed. Of the patients, 85% suffered from a malignant neoplasm. The average age at which euthanasia or assisted suicide was practised was 63.4 years (men) and 66.1 years (women). Under the age of 30 and above 85 euthanasia or assisted suicide was administered only rarely. Proportionally these procedures were applied to the same extent to men as to women. In about 20% of the cases an important secondary diagnosis was present. In conclusion, it is especially the malignant neoplasms that cause such suffering that euthanasia or assisted suicide are practised. The average age at which they are applied is considerably lower than that of the total of people who die in their own homes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922491 TI - [Euthanasia and assisted suicide by physicians in the home situation. 2. Suffering of the patients]. AB - In order to assess the suffering of patients who died at home and with whom family doctors participated in euthanasia or assisted suicide, an exploratory, descriptive, retrospective study was carried out regarding primarily the period 1986-1989. Data were collected via anonymous written inquiry among an at random sample of family doctors in North Holland (n = 521), and family doctors in the rest of the Netherlands (n = 521). With reference to the last case of euthanasia or assisted suicide they had encountered questions were included about physical and emotional suffering, signs and symptoms and life expectation. Correlations and differences were analysed by means of the chi2-test. The response to the inquiry was 67% (non-responders did not otherwise differ from responders): 228 (North Holland), 160 (rest of the Netherlands) cases could be analysed. Most patients suffered physically as well as emotionally. The most frequently mentioned aspect was 'general weakness or tiredness'. Also 'dependence or being in need of help', loss of dignity, humiliation' and 'pain' were often present to a (very) large extent. At the time the procedure was carried out the life expectation in almost two-thirds of the cases was less than 2 weeks; in 10% of the cases it was more than 3 months. For several reasons, this investigation reduces the possibilities of extrapolation. Further investigation is necessary to determine whether this picture of suffering is specific of this category of patients. PMID- 1922492 TI - [A serious complication of ritual circumcision of a 'buried' penis]. AB - The buried penis is a rare congenital anomaly in which a circumcision can result in deformity and functional disorder of the penis. We describe the case history of a one-year-old boy with this anomaly who underwent ritual circumcision by a layman. PMID- 1922493 TI - [Haste makes waste]. PMID- 1922494 TI - [Only ergotamine still helps]. PMID- 1922495 TI - [Autoimmune chronic active hepatitis: the potential need for long-term (life long?) maintenance therapy]. PMID- 1922496 TI - [DNA studies in families with hereditary forms of cancer]. PMID- 1922497 TI - [Application of radiofrequency energy as a new treatment method for arrhythmias]. PMID- 1922498 TI - [Series of articles on cell biology in medical perspective]. PMID- 1922499 TI - [Cell biology in a medical perspective. I. The cell viewed from a distance]. PMID- 1922500 TI - [Are there still indications for plasma transfusions?]. PMID- 1922501 TI - [Long-term survival following successful resuscitation outside the hospital]. AB - Between 1983 and 1989, 962 patients in Rotterdam were resuscitated outside hospital, of whom 240 (25%) could be discharged alive. A follow-up study was performed to determine prognosis in these patients. Data were collected through the Municipal Health Service, Population Registries, the hospitals where the patients were admitted, and the general practitioners. Of these 240 survivors of out-of-hospital resuscitation 80% survived after 1 year and 61% after 5 years. During the first year, 9% suffered from myocardial (re)infarction and 13% underwent coronary bypass surgery or angioplasty. Within the first three years after resuscitation 60% of the patients were readmitted to a hospital. Permanent or temporary neurological deficits were observed in 30 patients (14%). Patients with a primary arrhythmia without myocardial infarction had a poorer prognosis than patients with cardiac arrest in the context of an infarct. Survival was better in patients in whom resuscitation was initiated by physicians or ambulance nurses, than in patients resuscitated by lay-people. Multivariate analysis revealed that this difference was caused by a larger proportion of patients with a primary arrhythmia in the latter group. Since long-term prognosis after out-of hospital resuscitation is satisfactory, programmes for resuscitation courses should be stimulated. Such courses should be aimed predominantly at relatives of patients with known heart disease, police officers and children. PMID- 1922502 TI - [Results of liver transplantation in children; parents' opinion]. AB - Since 1982, the liver transplantation team of the University Hospital of Groningen has been carrying out transplantations in children. This article focuses on the experiences of the parents of 19 children who have undergone transplantation. An interview and two questionnaires were used to collect the data. Data concerned children's physical and psychosocial functioning and their daily behaviour. Five older children also filled in two questionnaires. In general, parents were positive about their child's functioning. When the interviews were analysed at an individual level, several problems were reported, however. These problems did not fall within one specific domain. As a consequence, the questionnaires did not show any significant differences between these children and a matched control group of healthy children. The parents of the children aged 1-3 yr were more positive about their children's functioning than the parents of the children aged 4-12 yr. The positive results should be assessed in the light of children's functioning before transplantation: when compared with pre-transplantation problems, present problems are of little significance. PMID- 1922503 TI - [Cervix smears with mild atypia classified as Pap-class IIIA: results of a changed policy]. AB - To evaluate the changed policy regarding cervical smears with mild atypia in the Netherlands (before 1988 classified as Pap II, thereafter as Pap IIIA), an descriptive study was carried out in the laboratory of gynaecological cytology Cyt-U-Universitair (University of Utrecht). All women who in 1988 had a first smear with mild atypia were included. After a follow-up period of 2 years the final diagnosis was noted. The results of the follow-up of cervical smears with mild atypia were compared with the follow-up results of moderate atypia. A selection was made of 477 women. In 55% of the cases no dysplasia was found during the 2 years of follow-up. In 12% of the cases severe dysplasia, carcinoma in situ or carcinoma was found. Compared with the smears with moderate atypia the dysplasia in the follow-up of mild atypia led to fewer cases of proven dysplasia. In addition the dysplasia in these cases was of a lower grade. The group of women referred to the gynaecologist after the smear with mild atypia was remarkably large (30%). As the results show, the policy of careful follow-up of women with mild atypia in the cervical smear has been a good one. It implies classifying mild atypia as Pap IIIA. As many women (55%) do not display cervical dysplasia within a 2 year follow-up period, the policy of making a repeat smear before referring appears justified. PMID- 1922504 TI - [Neurofibromatosis and a tumor of Vater's papilla]. AB - A male aged 57 is reported with neurofibromatosis presenting with a tumour in the periampullary region. Pathologic examination revealed a neuroendocrine tumour of the carcinoid type. A review of the literature suggests that neurofibromatosis patients are at significant risk for developing a periampullary tumour which is nearly always of neuroectodermal origin. To date, surgical excision is the only curative therapy. Therefore, early diagnosis is of major importance. In all patients with neurofibromatosis presenting with jaundice, gastrointestinal bleeding or abdominal pain, a periampullary tumour should be considered. A review is presented of the latest developments concerning the DNA-based mutation causing this disorder. In family members, DNA linkage studies should be carried out, and they should be periodically screened, e.g. with gastroduodenoscopy. PMID- 1922505 TI - [Medical practice in Africa; not essentially different]. PMID- 1922506 TI - [Comparative overview of postmortem organ donation in The Netherlands]. PMID- 1922507 TI - [Conflict at work and psychological disorders]. PMID- 1922508 TI - [Sleep and nocturnal air traffic]. PMID- 1922509 TI - [Experiences with electroconvulsive therapy]. PMID- 1922510 TI - [Perfusion scintigraphy of the heart]. PMID- 1922511 TI - [Immune response following preventive intracutaneous rabies vaccination]. PMID- 1922512 TI - [Gallbladder extirpation in The Netherlands; frequency, surgical mortality and postoperative complications (1987-1989)]. AB - In view of the fast-growing popularity of laparoscopic cholecystectomy, a retrospective analysis was made of 'traditional' cholecystectomy in the Netherlands in the period 1987-1989 (data provided by the Health Care Information Centre Foundation), as compared with the period 1979-1981 (data provided by the Medical Registration Foundation). As regards frequency, the number of cholecystectomies had decreased by 25.5% compared with the period 1979-1981. The number of cholecystectomies with exploration of the choledochus had decreased by 43.8%. The surgical mortality in the period 1987-1989 amounted to 1.4%. Postoperative complications, including wound infections, were relatively infrequent, occurring in 4.3% and 1.5%, respectively, of the patients. Acute cholecystitis, age greater than 70 years and choledochus exploration proved to be risk factors with substantially higher surgical mortality and postoperative morbidity. PMID- 1922513 TI - [Erroneous diagnosis 'neonatal hypoglycemia' due to incorrect preservation of blood samples]. AB - The high frequency of neonatal hypoglycaemia found in the St. Catherine's Hospital, Eindhoven [corrected], (8.2% of all newborn infants had values of 1.8 mmol/l glucose or less) promoted us to test the effects of the different conditions of blood preservation before measuring in a consecutive series of 18 newborn infants at risk for hypoglycaemia. When blood was preserved in microtest tubes coated with sodium fluoride (NaF) and measured after 1 hour at room temperature, the glucose level decreased by 7 to 36%. Storage on melting ice for one hour prevented this decline completely. In our hospital sodium fluoride coated microtest tubes are used. They were found to contain various concentrations of NaF, ranging from 0.85 to 2.65 mg/ml. In a 2nd experiment with cord blood from 8 patients, we proved that a concentration of 16 mg/ml sodium fluoride was necessary to inhibit glycolysis and to prevent a fall of plasma glucose. The rapid determination of blood glucose values, i.e. within 10 minutes after the blood sample is taken, decreased, as expected, the frequency of hypoglycaemia in the newborn at risk. PMID- 1922514 TI - [Electroconvulsive therapy in a peripheral hospital]. AB - The findings are reported of a retrospective study of 25 patients with a refractory depression in the restricted sense, admitted for ECT to a psychiatric department of a general hospital (Rijnstate, Arnhem). The results after ECT and the course during 2 years after the treatment were inventoried and compared with data in the literature. At discharge, 12 patients were classified as 'recovered', 9 were improved and four showed little or no change. After two years, 4 patients had died, one of them having committed suicide. Of the 22 follow-up patients 19 patients were at home: 15 could be classified as cured, 3 considered their condition improved and 4 were unchanged. Twelve were found to have had a recurrence of depression which in ten of them could be controlled with antidepressive drugs or ECT. ECT as a part of treatment of depressions may be regarded as useful and may safely be administered in a psychiatric department of a general hospital. PMID- 1922515 TI - [Generalized urticarial exanthema caused by subcutaneous injection of methylene blue]. AB - A case of generalized urticarial rash due to subcutaneous administration of methylene blue for lymphangiography is presented. The urticarial lesions were coloured blue. PMID- 1922516 TI - [Priorities in prevention]. PMID- 1922517 TI - ['Healthy life expectancy', a contemporary measure for public health]. PMID- 1922518 TI - [The useful effect of serological screening programs for syphilis in pregnant women in Amsterdam in the period 1985-1989]. PMID- 1922519 TI - [Do indications for transfusion of plasma still exist?]. PMID- 1922520 TI - [Cerebral infarct]. PMID- 1922521 TI - [Children with an attention deficit disorder with hyperactivity; the role of drugs in treatment]. PMID- 1922522 TI - [Conservative therapy frequently indicated in blow-out fractures of the orbit]. PMID- 1922523 TI - [Patellar chondropathy in family practice]. PMID- 1922524 TI - [Work disability in migrants: is the physician helpful?]. PMID- 1922525 TI - [Dry bed training and diagnosis in nocturnal enuresis]. PMID- 1922526 TI - [Cell biology in medical perspective. II. Macromolecules of the cell]. PMID- 1922527 TI - [Clinical relevance of the measurement of insulin=like growth factors in plasma]. PMID- 1922528 TI - [The statistics of survival curves]. PMID- 1922529 TI - [Cholera in 1991]. PMID- 1922530 TI - [A survey of the diagnostic policy in nocturnal enuresis]. AB - A written enquiry regarding the current diagnostic policy in nocturnal enuresis was conducted among paediatricians (response 38%, n = 22) and urologists (response 49%, n = 23) while an enquiry by telephone was held among GPs (n = 40) with the same questions. With reference to three case histories, the question was asked what supplementary examinations, if any, would be carried out. All respondents showed a tendency to perform extensive urological examinations. Since bedwetting in most cases is not associated with demonstrable anatomical or functional abnormalities, this is incorrect for medical reasons, even apart from the costs involved. PMID- 1922531 TI - [Dry bed training in nocturnal enuresis]. AB - In order to determine the prevalence of bedwetting, in the period September 1987 June 1989 an investigation was conducted among 1882 pupils of 15 primary schools in a rural area of the Netherlands. The investigation coincided with the periodical medical examination for which all pupils of these groups were invited and for which over 99% reported. In addition to this epidemiological study, a study was made of the effect of dry bed training, as a part of youth health care, in 36 children with nocturnal enuresis. Of the children examined, 8% wet their beds at least once a week, boys twice as often as girls. The secondary form of nocturnal enuresis occurred mostly in those aged 7-8 (44%) and mostly after certain events such as start of the school year, family problems or hospitalization. The proportion of bedwetting children with a parent with a history of nocturnal enuresis in youth was large: 56%. Of the girls with nocturnal enuresis, 25% had had a urinary tract infection as against 0.4% of the control group. Nocturnal enuresis often caused emotional stress in child and parents. The success rate of the dry bed training was 86%. Most children were dry within two months; 32% had a--frequently transient--relapse. After six months, 75% of the children who had had dry bed training remained dry at night. Group dry bed training appears a suitable method for children with nocturnal enuresis from age 8 when other methods (including the pad and buzzer) are unsuccessful. The training is feasible outside hospital and is an appropriate part of the tasks of youth health care. PMID- 1922532 TI - [The spontaneous course of otitis media with effusion in young children]. AB - OBJECTIVE: Description of the natural course of otitis media with effusion (OME) in pre-school children. DESIGN: Longitudinal follow-up study. SETTING: Nijmegen, the Netherlands; at the children's home address. PATIENTS AND METHODS: A cohort of 1439 children born in the period September 1982 to August 1983 and living in Nijmegen at their second birthday were invited for participation in serial tympanometric screening with a three-monthly interval. Each child was measured 9 times from age 24 to 48 months. A flat tympanogram was considered to be indicative of OME. Participation was 92%, but interpretable tympanograms were taken in 2242 ears (first round) to 1990 ears (last screening). Data of 56 children treated with grommets were excluded from analysis. RESULTS: Longstanding OME (at least 4 flat tympanograms in a succession) was seen in 9.3% (95%-CI 7.0 11.6) of ears. In another 23.4% (20.1-26.8) of ears OME was found 2 or 3 times at subsequent screenings. Single or recurrent flat tympanograms were seen in 20.4% (17.2-23.6) and 11.6% (9.0-14.1) of the ears respectively. The probability of recovery over time was well described with a simple function of a 50% improvement every 3 months. In addition, 50% of the recovered ears showed one or more recurrences of OME. CONCLUSION: OME appears to run a very fluctuating course with a strong representation of short disease episodes and high rates of recovery and remission. The data confirm the results of others. A common interpretation, i.e. a sharp reduction of the recovery rate after three months, appears to be false. A 50% improvement rate every 3 months fits the data equally well. This study does not provide information about the sequelae of OME at school age. PMID- 1922533 TI - [Generalized mastocytosis; to be considered following resuscitation]. AB - This case report describes a male patient aged 44 with recurrent hypotensive shock and severe pulmonary obstruction. The diagnosis of systemic mastocytosis was suggested by the presence of small pigmented maculae (urticaria pigmentosa) and intolerance to NSAIDs. The diagnosis was confirmed by microscopic investigation of the pigmented maculae and bone. The patient was advised to avoid certain foods and drugs and has so far been free of symptoms. In patients with hypotensive shock and (or) severe pulmonary obstruction without a clear cause, systemic mastocytosis should be included in the differential diagnosis. PMID- 1922534 TI - [Desmopressin and nocturnal enuresis]. PMID- 1922535 TI - [Eurothemes. Is Eastern European commerce in health care even worse than that from and within the West?]. PMID- 1922536 TI - [How do blisters develop after contact with hogweed and which treatment is indicated?]. PMID- 1922537 TI - [Mass screening for breast cancer in women younger than 50; a literature review of the probable effect on mortality]. PMID- 1922538 TI - [Influenza in the 1990/'91 season; composition of vaccine for the 1991/'92 season]. PMID- 1922539 TI - [Light on medicine: medical illustrations in the Nederlandsch Tijdschrift voor Geneeskunde, 1857-1925]. PMID- 1922540 TI - [The Nederlandsch Tijdschrift voor Geneeskunde and the practice of medical science in The Netherlands (1857-1896); light under a bushel?]. AB - The Nederlands Tijdschrift voor Geneeskunde came into being first of all because of the need for a medium to help 'elevate' the medial profession. Since the scientific foundation of medicine constituted an important argument for the aspired raising of status, it is understandable that the editors particularly also wanted to make the journal a forum of medical science in the Netherlands. In this--much to their dissatisfaction--they failed to succeed in the first 40 years in spite of a number of reorganizations intended to get a better grip on the results of medical-scientific research in the country. Not until the turn of the century did a change set in: the medical faculties, where the practise of science came to achieve some significance and the Journal began to grow towards one another. At the same time it also began to be realized that research workers cannot be expected to publish their findings primarily in a journal in the Dutch language. PMID- 1922541 TI - [Medical illustrations and technique; 19th-century graphic procedures and their suitability fo scientific illustrations]. AB - For a publisher of a scientific journal around 1850 there were various possibilities with regard to illustration technique. The ultimate choice was determined by considerations of necessity, clarity but particularly also, price. In the Nederlandsch Tijdschrift voor Geneeskunde the last-mentioned aspect appears to have been very weighty, especially in the beginning. Newly introduced techniques permitting better detail were often applied relatively late and infrequently. Photography proved to be an important aid in illustrating, although the printed reproduction was initially primitive and of poor quality. Improvement of the financial situation of the Journal was immediately reflected in an increase of the number of illustrations. PMID- 1922542 TI - [From drawing and photograph to printed illustration; engravers, lithographers and printers in action for the Nederlandsch Tijdschrift voor Geneeskunde to 1920]. AB - From 1857 to 1920 a number of engravers and lithographers supplied the Nederlandsch Tijdschrift voor Geneeskunde with illustrations. Two lithographers may be regarded as regular contributors to the Journal. They were A.J. Wendel of Leiden, who from 1859 to 1875 was active as house lithographer, and the Amsterdam lithographer C. Mooy from 1883 to 1910. The new techniques of mechanical reproduction of photographs in printing slowly but surely replaced the lithos and wood engravings. PMID- 1922543 TI - Photographing medicine. AB - This article addresses the issue of conventions in medical photography since it was developed 150 years ago. It points out, that precisely those photographs that seem to break with conventions, might become very useful to the historian of medicine. Especially photographs of medical interventions intended for a larger, non-professional audience often do not portray those medical activities, that take up most time and energy in modern medicine, i.e. the management of chronic diseases. Photographs can help to document the tension between health policy and everyday medical practice. PMID- 1922544 TI - [Images of normal life; physiological illustrations and medical 'translation' in the Nederlandsch Tijdschrift voor Geneeskunde in the 19th and early 20th century]. AB - The Nederlandsch Tijdschrift voor Geneeskunde, the leading Dutch medical journal, could easily be called the most important medium for dialogue between Dutch physiologists and clinicians in the second half of the nineteenth century. The journal's contents demonstrate the large-scale process, by which through applying a range of instruments, numerous bodily functions were 'translated' into a variety of graphic forms, both for clinical and research usages. PMID- 1922545 TI - [Learning to read; roentgen photos and the Nederlandsch Tijdschrift voor Geneeskunde]. AB - Reading articles from the earliest years of roentgenology, shortly after 1896, we find that reading a roentgenogram was an explicit mixture of technique, anatomy, clinical data, patient, pathology and shadow. Reading roentgenograms was not just deciphering the shadows in terms of an underlying, stable 'natural world', it was an active construction and representation of 'normal and pathological'. The articles on the 'new photography' in the Nederlandsch Tijdschrift voor Geneeskunde are not just a passive representation of this process: they also enable the contemporary to follow the construction in all its aspects and to use it in his own work with rays and photographs. PMID- 1922546 TI - [Pathological anatomy in The Netherlands showing new ways]. AB - In the early nineteenth century microscopical examination gained a lasting place in medicine, due especially to support by a more dynamic way of thinking in pathology. Morbid anatomy discovered new ways of examination which were reflected in the illustrations. In the first 70 volumes of the Nederlandsch Tijdschrift voor Geneeskunde the artist still played an important part in representing microscopical findings; it was only recently that this part was definitely terminated. Illustrations of pathological processes and structures published in the Journal are represented, subdivided according to the various disciplines. PMID- 1922547 TI - [Diseases charted in the Nederlandsch Tijdschrift voor Geneeskunde, 1857-1880]. AB - On the basis of the miasma theory and the contagion theory a comparison is presented of the 'cartography' in the epidemiology of the early years of the Nederlandsch Tijdschrift voor Geneeskunde and the present. The importance of publication of 'disease charts' then and now is illustrated with examples. Understanding, with the aid of charts, of the typical patterns of distribution of diseases, infectious and noninfectious, is still a cornerstone of their control. PMID- 1922548 TI - [The patient exhibited; clinical demonstration and clinical lessons in the Nederlandsch Tijdschrift voor Geneeskunde]. AB - The evolution of clinical demonstrations and of the illustrations is discussed, with reference to the importance of sharpening observation as a medical method. It is especially in the section 'Clinical Lessons' in the Nederlandsch Tijdschrift voor Geneeskunde that the way in which the patient is shown in illustrations is considered in detail, including the question to what extent limits were imposed on what was considered permissible in illustrations. PMID- 1922550 TI - Above all, do no harm. PMID- 1922549 TI - Single payor, multiple tiers. PMID- 1922551 TI - A microbiologic survey of long term care urinary catheters. AB - Culture and sensitivity data were collected on over 500 isolates from indwelling urinary catheters in 23 Nebraska long-term care facilities. Four percent of all nursing home patients had indwelling urinary catheters. The prevalence of bacteriuria in catheterized patients was 79%., and the most frequent isolates were E. coli, Proteus mirabilis, and Enterococcus species. Thirteen percent of catheterized patients were receiving systemic antibiotics, and 85% had at least one urinary bacterial isolate resistant to the antibiotic being administered. Antibiotic resistance correlated positively with a number of factors in the long term care institutions, including size and skill level. PMID- 1922552 TI - Airborne pollen survey for Lincoln, Nebraska: I. Trees. AB - Pollen counts in 1988, 1989, and 1990 revealed 14 different tree pollen types. The main tree pollination season in Lincoln extends from late February or early March through the end of May. First linden and then pine and juniper extend the trees through October. The sequence of flowering for the plants is similar to that found in other regions of the country. The highest counts (peaks of ca. 1000 grains/m3) are in March, April, and May when the largest number of trees are in bloom. Counts fall through June (highest ca. 300 grains/m3) and July (highest at ca. 35 grains/m3) when grasses and some weeds are flowering. PMID- 1922553 TI - Airborne pollen survey for Lincoln, Nebraska. II. Grasses. AB - Pollen counts in 1988, 1989, and 1990 revealed the presence of grass pollen from April through October. Grass pollen counts begin to rise in late May and early June and peak in the middle of that month. Counts fall in July but rise again to a lower peak in August and early September. PMID- 1922554 TI - Airborne pollen survey for Lincoln, Nebraska. III. Weeds. AB - Pollen counts in 1988, 1989, and 1990 revealed 16 weed pollen types. The weed pollination season in Lincoln extends from March through October. Very low amounts of pigweed-type and nettle pollen appear in April. Dock pollination begins in May. June has the greatest diversity of weed types and moderately high total counts (highest total June counts ca. 300 grains/m3). July is low in both diversity and absolute numbers of pollen grains (highest total July counts ca. 35 grains/m3). In early August pollen counts begin to rise with the primary pigweed type pollination season and the first ragweed pollen. Ragweed pollen peaks in the last week of August and first week of September with more than 460 ragweed grains/m3 and total counts of more than 780 gr/m3. PMID- 1922555 TI - Skyrocketing costs of medical care in the United States. PMID- 1922556 TI - Cocaine: a historical and modern perspective. PMID- 1922557 TI - The escalating cesarean section rate: a 25 year experience at the University of Nebraska Medical Center. AB - The cesarean section rate at our medical center has increased gradually from 9.1% in 1965 to 21.9% in 1989, which is lower but similar to national trends. This upward trend was reversed in 1990 by more strongly encouraging vaginal births after cesarean section, attempting more vaginal deliveries in select cases of breech presentations, and complying with national guidelines for defining fetal distress and dystocia. Recommendations are offered for the development of statewide guidelines for peer review and quality assurance. PMID- 1922558 TI - Extension of renal cell carcinoma into the vena cava with concomitant coronary artery disease: surgical considerations. AB - Surgical removal of renal cell carcinoma with extension into the inferior vena cava can be a difficult operation. Cardiopulmonary bypass and circulatory arrest have been used to assist in resection of tumors that extend into the vena cava above the level of the hepatic veins. Coronary artery disease is a common problem and may present together with renal cell tumors. A patient with left main coronary artery disease and a renal cell carcinoma extending into the vena cava provides a management challenge. We present such a case and discuss the surgical options. PMID- 1922559 TI - Present day diagnosis. 1929. PMID- 1922560 TI - Blood transfusions and the Jehovah's Witness--neonatal perspectives. PMID- 1922561 TI - [A cross-correlational analysis of the background neuronal pulse trains in surviving slices of the guinea pig neocortex]. AB - Cross-correlation analysis of interdependence of the background spike activity was carried out for pairs of adjacent neurons simultaneously recorded in the incubated slices of the neocortex of guinea-pig. Statistical correlation of spike discharges was detected in 16 out of 26 recorded pairs of the neurons. Significant correlation was observed mainly in the range of +/- 100 ms from the null point. Cross-correlation had symmetric or asymmetric maxima up to 150 ms long and negative shifts up to 200 ms long. More complex positive-negative types of cross-correlations were also obtained. The data were compared to those known from other authors for the intact brain. The contribution of intrinsic intracortical interactions and extrinsic afferent influences in these correlations of activity is discussed. PMID- 1922562 TI - [The involvement of intracellular calcium in the sensitization of command neurons in the defensive behavior of the edible snail]. AB - Examinations carried out on command neurons of defensive behaviour of snail carried out using electrophysiological methods and a chlorotetracycline fluorescent probe have revealed that a single sensitizing action induces alterations of electrical neuronal activity and bound calcium (Ca-C) level in cells. An initial increase of the Ca-c amount (the first 15-20 min after the sensitizing action) coincides in time with depolarization, enhancement of plasma membrane excitability as well as with a decrease of amplitude and duration of the IPSPs induced by sensory stimulations. Repeated pronounced increase of the Ca-c level develops 50-60 min after the sensitizing action and correlates with facilitation of neuronal responses to sensory stimuli. Alteration of the Ca-c level in command neurons of defensive behaviour in the course of sensitization development differed from the previously described Ca-c shifts in the same cells in the course of habituation development in dynamics and direction. PMID- 1922563 TI - [The background impulse activity of the neurons of the nucleus fastigii in the rat cerebellum]. AB - Background impulse activity (BIA) of fastigial nucleus (NF) of the rat cerebellum has been analyzed. Prevalence of stationary impulse flows (IFs) and their irregularity of various types are found out, regular components of IF occurring frequently. Nonstationary IFs are detected as well, but they are studied only in 15% of a total number of units. A serial correlation analysis of duration of interspike intervals (ISIs) in case of stationary IFs and nonstationary ones permits stating six main varieties of ISI dynamics: 1) independent accidental distribution of impulse sequences; 2) irregular changes (acceleration or deceleration) of IF rate with positive correlation coefficients (CCs) in a range of initial five ISI orders; 3) irregular appearance of combined short and long intervals with negative CC in neighbouring ISIs; 4) periodic changes of IF rate, in particular, as grouped discharges varying in total duration and frequencies (4 and 5 IF varieties); 5) in case of negative values of CCs of the first order the recorded IFs in the primary complex serial correlograms have been determined as the 5th dynamic variant; and, finally, 6) prolonged cycles of BIA acceleration or deceleration with positive CCs up to 10-20 and higher orders. One third of NF units recorded have other BIA variations with the characteristics similar to types 2-3 and 6 mentioned above. They are considered to be induced by various correlations existing also at high-order ISIs. Formation of IFs registered and their pattern changes can serve as an adequate index of current state of cellular activity recorded extracellularly from small size cells of the CNS. PMID- 1922564 TI - [The effect of stimulation of the ocular muscles on the formation of visual responses in the cat lateral geniculate body]. AB - It has been shown in acute experiments on anesthetized cats that stimulation of the ocular muscles by single current pulse caused different changes in formation of negative and positive components of the visual response of the lateral geniculate nucleus. It was established that character of those changes depended on the interval between conditioned muscular and tested light stimuli. PMID- 1922565 TI - [The action of a short inhibitory volley on human firing motoneurons (an experiment and a model)]. AB - The influence of a short inhibitory volley on firing motoneurons of soleus and ext. carpi uln. was studied in human experiments and the results obtained were used as a basis for simulation. An increase of the interspike interval (ISI) depended on the timing of inhibitory volley arrival and silent period (SP) duration was studied. The ability of the individual motoneuron to respond to inhibitory volley by prolongation of ISI influenced the SP duration. Two parameters were crucial: the duration of the part of ISI where the inhibition was efficient in increasing the ISI (d) and the maximal increase of ISI (delta x max). The latter corresponded to the inhibitory volley arrival at the very end of ISI. If d less than delta x max the SP = d; if d greater than delta x max the SP = delta x max. In the case of variable ISIs those relations should be applied to the smallest ISI among the ISI distribution. Therefore the SP duration depended not only on the mean ISI of a motoneuron, but on ISI variability as well. PMID- 1922566 TI - [The manifestation of the hysteresis effects of muscle contraction in the cortically evoked coactivation of muscle antagonists]. AB - Hysteretic after-effects of muscle contraction were studied on unanaesthetized cats during intracortical microstimulation of two sites in the motor cortex. Equilibrium in the joint-external load system was shown to be dependent on the order of stimulation of the sites in the motor cortex. Coactivation of antagonistic muscles led to an increase in both the joint stiffness and uncertainty of the equilibrium value of the joint angle. PMID- 1922567 TI - [Changes in the neuronal background activity of the central gray substance of the midbrain to motor cortex stimulation in rats]. AB - Motor cortex stimulation induced inhibition of the background activity (BA) in 47% periaqueductal gray neurons, excitation--in 20% and had no influence in 32% neurons. Most of the activated neurons (67%) had the 3d type of BA. Neurons with the 1st type of activity did not respond to the cortex stimulation. PMID- 1922568 TI - [The brain stem pathways of locomotion initiation]. AB - The data about structural organization, connections and different ways of activation of the brain stem locomotor regions are offered in the review. The specificity of the locomotor regions and pathways of their influence on the spinal locomotor generator is discussed, the role of the reticular formation is elucidated. It is suggested that side by side with the multilevel system of the locomotion initiation, which has an output on the spinal cord via medial reticular formation, nonspecific afferent activation of the brain stem is also very significant. PMID- 1922569 TI - Strategies of reducing the carcinogenic risk of cytostatic agents on the basis of bioassay evaluation. AB - This article described strategies that can be used to reduce the carcinogenic risk of cytostatic chemotherapy and summarizes our recent experimental results. Reduction of neoplasms caused by the carcinogenic potency inherent in cytostatic agents can be obtained. (A) by chemical modifications such as: (1) exchanging a chlorine atom in N, N'-bis-(2-chloroethyl)-N-nitrosourea (BCNU) in the chloroethyl group at N'-position for a hydroxyl group to form the less carcinogenic analog N-(2-chloroethyl)-N'-(2-hydroxyethyl)-N-nitrosourea (HECNU); (2) linking chlorambucil to the steroid prednisolone to obtain a conjugate (prednimustine) with distinctly lower carcinogenic potential than chlorambucil; (3) progressive ring halogenation of phenyl-triazenes to generate agents with decreased long-term toxic risk; (B) by replacing cyclophosphamide within the carcinogenic drug combination of cyclophosphamide, methotrexate and 5 fluorouracil (CMF) by vincristine to form the combination VMF which has no detectable carcinogenic potential; (C) by coadministration of cyclophosphamide and mesna to achieve a dose-related reduction of cyclophosphamide-induced urinary bladder carcinomas; (D) by administration of dinaline, a compound which reduces the spontaneous incidence of malignant tumors in rats. These examples demonstrate that the carcinogenic risk of single agents and drug combinations used for antineoplastic chemotherapy has successfully been reduced, as assessed in long term bioassays. Such strategies should be considered in the treatment of patients with long life expectancy following cytotoxic chemotherapy. PMID- 1922570 TI - C-band heterochromatin variants in individuals with neoplastic disorders: carcinoma of breast and ovary. AB - C-band heteromorphism was studied in 106 females, including 71 patients with breast cancer or ovarian cancer. Size heteromorphism and localization variants (inversions) were scored separately. Compared to 22.86% of controls, 70.42% of the cancer patients were heteromorphic for the size of C-band. The localization variants were observed in only 8.57% controls, whereas 42.25% of cancer patients carried such variants. Taking both the criteria together, compared to 31.43% controls, 80.28% cancer patients were C-band heteromorphic. The present study supports the reported association between presence of C-band heteromorphism and occurrence of a malignant disease. PMID- 1922571 TI - Cytogenetic analysis and population study in P3HR-1 cell line derived from Burkitt's lymphoma. AB - P3HR-1 cell line derived from Burkitt's lymphoma was chosen as a model for studying the development of the cell population during long-term cultivation from the cytogenetic point of view. Fifty G-banded karyotypes at two different passage levels were analyzed, using also C-, Q- and Ag-staining. The modal chromosomal number at the 15th passage was 49, at the 75th passage 48. At the 15th passage considerable heterogeneity of karyotypes was found. Only four metaphases had an identical karyotype: 49, XY, +7, +21, +psu dic mar, dup(1) (q21q42), del(1) (p ter----q23:), t(8;14) (q24;q32), 16qh+. This clone turned out to be important in the further development of the cell population. At the 75th passage there was only one metaphase with this karyotype. Fifteen metaphases (30%) revealed a karyotype with only one difference from the karyotype mentioned above: deletion of a part of the short arm of one chromosome 7. Further 16 metaphases (32%) had 48 chromosomes, where one chromosome 7 was missing in comparison with the above mentioned karyotype, and 3 metaphases (6%) with 48 chromosomes, where the loss of chromosome 21 and deletion of a part of the short arm of one chromosome 7 were found. These three clones could have originated from the clone described at the 15th passage through loss of a whole or part of chromosome, or both; i.e. the clone forming 8% of the cell population at the 15th passage gave rise to 70% of the cell population during 60 passages in vitro (30 weeks of cultivation). Cytogenetic analysis at two different passages enables the observation of the dynamic changes in the cell population. A wide gamut of cell clones enables heterogenous selection influences in vitro. PMID- 1922572 TI - Possible relationship between abnormal melanosome structure and cytotoxic phenomena in malignant melanoma. AB - Melanogenesis has been regarded as a hazard for pigment cells which are endangered by reactive quinones and semiquinones generated by this process. Normally the potentially cytotoxic species are confined to melanosomes by a limiting membrane and thus separated from the rest of the cell. Our electron microscopic investigation has demonstrated the presence of abnormal and incomplete melanosomes in human melanomas from epidermal and mucosal sites, in melanoma metastases, and in B16 mouse melanoma. We conclude that significant leakage of reactive melanin precursors including free radical species may occur from aberrant melanosomes in pigmented tumors. This would be expected to be reflected by fully extended physiological scavenging mechanisms, and by local and distant manifestations of cytotoxicity: Among these manifestations is free radical damage to the liver, detected by a thiobarbituric acid-reactive substances assay, in B16 melanoma-bearing mice. The efflux of toxic species from abnormal melanosomes may explain both the observed frequent occurrence of necrosis in melanomas and the therapeutic efficacy of tyrosinase substrates and may also be one of the factors influencing the extent of melanogenuria. PMID- 1922573 TI - HPLC analysis of platinum cytostatics. AB - High performance liquid chromatography (HPLC) with diode array detector (DAD) was applied for the separation of platinum cytostatics (cisplatin, carboplatin and oxo-carboplatin). Their stabilities were studied in water and the influence of chloride anions, pH, temperature and time was discussed and rate constants of the aquation reactions at different conditions were calculated. Ligand exchange reactions cisplatin----carboplatin were evaluated using HPLC-DAD system. Detection limits for all studied cytostatics were determined and extraction recoveries for carboplatin in clinical samples (serum) were demonstrated for a wide range of concentrations together with the relative standard deviations. The solid-phase extraction procedure was recommended for clinical sample analysis represented by a model mixture and real patients' samples. PMID- 1922574 TI - Determination of suramin in clinical samples using HPLC. AB - High-performance liquid chromatography (HPLC) was applied for the determination of suramin levels in serum samples from cancer patients treated with this drug. Ion-pair chromatography in combination with the deproteination procedure extraction and hydrolysis of complex serum proteins-suramin were recommended. Extraction recoveries and linearity for wide concentration range were evaluated. Detection limit of suramin in serum samples was determined (0.5 micrograms/ml), and concentration curves as the dependences of suramin concentration levels and time have been illustrated. Chromatographic conditions were optimized for minimal analysis time (max. 10 min) and suitable chromatographic resolution (Rij greater than 1.25). PMID- 1922575 TI - Prognostic value of the epithelial membrane antigen (EMA) in the case of Hodgkin's disease. AB - The study deals with the results obtained from 155 lymph node biopsies of patients suffering from Hodgkin's disease (HD) who were treated by MOPP and radiotherapy in the same establishment. The specimens in paraffin have been examined for the presence of antigens using several monoclonal antibodies, particularly epithelial membrane antigen (EMA). There exists no correlation between the immunophenotypes towards EMA and histological types. Thirty-three patients whose responses were EMA (+) have the assurance survival more than 10 years on the level 32.4% while those 122 patients with EMA(-) had the same survival on 90% level (p less than 0.001). Thus a new prognostic tool has been found which enables to detect the likely therapeutic failures in the case of Hodgkin's disease. PMID- 1922576 TI - Towards improved cancer diagnosis and treatment founded on current developments in the basic sciences: options for intensified European efforts. A consensus paper. Research Branch of the European Organization for Research and Treatment of Cancer (EORTC). PMID- 1922577 TI - [The voice of psychiatry in concert with medical specialties]. PMID- 1922578 TI - [Familial aggregation of psychiatric disorders and the consequences for the psychiatric diagnosis]. AB - Schizophrenic and affective disorders, anxiety disorders, and alcoholism show familial aggregation; the impact of familial aggregation on the classification and etiology of psychiatric disorders is discussed. Ideal diagnostic schedules should a) identify conditions with a substantially increased familial risk and b) reach diagnostic homogeneity in multiplex families. A review of the literature shows a) that age at onset, long-term course and comorbidity modify familial risks and should therefore be given more attention in diagnostic schedules and b) that the heterogeneity of disorders in multiplex families draws the validity of currently used diagnostic schedules into question. Against this background the hypothesis of "unitary psychosis" is discussed. PMID- 1922579 TI - [Differential diagnosis of dementia diseases. A prospective clinical study with neuropathologic diagnostic verification]. AB - We present clinico-pathological correlations for a consecutive series of 44 demented patients in the Vienna longitudinal study on dementia. Prospective clinical diagnosis used the DSM-III-R and the NINCDS-ADRDA criteria. Not only the clinical, but also the neuropathological diagnosis of DAT is based on exclusion criteria, and depends on the interpretation of minimal vascular lesions. Although we did not exclude atypical cases from the study, 80% of diagnoses could be validated at autopsy. Nevertheless, our set of clinical criteria needs further validation in patients in the earliest stages of dementia. PMID- 1922580 TI - [Neuronal nets]. AB - Neural networks are used as models of cognitive systems. On the basis of results from brain research, the processing of knowledge and information can be conceived as occurring through parallel interaction of multiple but simple and uniform processor elements in a network structure. In these 'neural networks' knowledge is stored in a distributed way throughout the network and subjected to parallel processing. According to Hebb's concept of synaptic plasticity, the process of learning is based on the strengthening of the links between the processing elements. The implementation of network models in electronic data processing systems allows for simulation of cognitive phenomena such as learning and forgetting or abilities such as recognition of acoustical or optical patterns, in a more efficient way than conventional computer programming. Neural network modelling can help to understand the abilities and disorders of the brain. PMID- 1922581 TI - [Principles of insight and relations between insight and control]. PMID- 1922582 TI - [The pilot project "Soteria Bern" in treatment of acute schizophrenic patients. I. Conceptual principles, practical realization, clinical experiences]. PMID- 1922583 TI - [Changes in the German psychiatric drug dependence definition]. AB - Experience recorded in the psychiatric/psychotherapeutic sector with young persons dependent on drugs, with compulsive gamblers and, especially, with alcoholics, some of them in relatively early stages of the disease, has led to shifts in attitudes to the problem of addiction among German-speaking psychiatrists and thus to a shift in their understanding of the term addiction (in the sense of addictive illness). The concept of addiction was extended when the existence of nicotine dependence was recognized. Prevention of addiction is an urgent priority, and therapy must be instituted as soon as possible; these aims mean that addiction (dependence) must be clearly and objectively defined without reference to value-systems, but also comprehensively. The sign of addiction that is most important in pracice, as it is fairly specific and occurs at an early stage, is the phenomenon of loss of control. PMID- 1922584 TI - [Differential typology among patients with hard and soft suicide methods]. AB - Two samples of patients admitted during one year after suicide attempts were compared: patients of the University Surgical Department in Heidelberg and a random sample of those who were admitted to the detoxication ward of the University Department for Internal Medicine. The frequency of patients who used "hard" methods was 10% of those using "soft" methods. Patients with hard suicide methods displayed more social desintegration, were more often psychiatrically ill, had a shorter presuicidal phase, a shorter time span from decision to execution of the suicidal attempt, more negative self-esteem and more chronic suicidality. Aggressiveness was low in both groups. Although the number of patients with "hard" suicidal methods is small and does not justify a special service in the Surgical Hospital, these patients need particularly careful supervision because of their psychopathological and psychosocial profile. PMID- 1922585 TI - [Endogenous paranoid-hallucinatory syndrome caused by Borrelia encephalitis]. AB - We describe a case with no neurological signs but marked psychiatric symptoms induced by borrelia burgdorferi, whose clinical picture was indistinguishable from an endogenous schizophrenia. The symptoms within one week under antibiotic treatment with ceftriaxon, but afterwards the patient showed a mild organic brain syndrome. The case demonstrated the aetiologic nonspecificity of paranoid symptoms and hallucinations and emphasizes that in psychotic patients without psychiatric history additional diagnostic measures should be performed. PMID- 1922586 TI - [Successful treatment of a therapy-refractory compulsive syndrome by electroconvulsive therapy]. PMID- 1922587 TI - [Musical hallucinations in hearing loss in the aged]. AB - An 83-year-old woman experienced the abrupt onset of musical hallucinations. She had had long-standing progressive hearing loss due to otosclerosis. The clinical, psychopathological and pathogenetic aspects of this syndrome are discussed by means of a review of the literature. PMID- 1922588 TI - [Comment on the contribution by K. M. Flechtner, W. Gaebel and H. Helmchen. Life support measures versus death with dignity in demented patients]. PMID- 1922589 TI - Colon cancer, some progress at last. PMID- 1922590 TI - Severely impaired postprandial gallbladder emptying despite unchanged cholecystokinin release in the early phase of biliary colic. AB - In the present article we report transitory severely impaired postprandial gallbladder emptying preceding biliary colic in a cholesterol gallstone patient. Gallbladder emptying 1 wk before and 3 wk after the biliary colic was normal. Treatment with ursodeoxycholic acid led to increased fasting gallbladder volumes, but the postprandial residual volume did not change. Postprandial cholecystokinin release appeared not to change during ursodeoxycholic acid treatment or during biliary colic. PMID- 1922591 TI - Hyperthyroidism due to inappropriate secretion of thyroid-stimulating hormone: diagnosis and management. AB - The case histories of three patients with hyperthyroidism due to overproduction of thyroid-stimulating hormone (TSH) by the pituitary gland are described. In the first patient treatment with the T3-metabolite 3,5,3'-triiodothyroacetic acid (TRIAC) led to complete clinical and biochemical normalization. In the second patient treatment with the dopaminergic agonist bromocriptine led to a temporal amelioration of hyperthyroidism. In the third patient, who was the only one with a proven pituitary adenoma, hypersecretion of TSH could be controlled by administration of the somatostatin analogue octreotide. It is emphasized that patients with this disorder should preferably not be treated with thyrostatic drugs, radioactive iodine or thyroid surgery. The success rate of these treatment modalities is lower than normal, they may lead to an increase of goiter size, and they potentially may promote growth or development of a TSH-producing adenoma. Treatment should be aimed at diminishing TSH hypersecretion. PMID- 1922592 TI - No effect of the long-acting somatostatin analogue octreotide in patients with insulinoma. AB - The efficacy of subchronic (3 weeks) treatment with the long-acting somatostatin analogue octreotide was studied in four patients with symptomatic benign insulinoma. No clinical or biochemical effect on serum glucose, insulin, C peptide or glucagon was observed in all four patients despite clearly detectable serum levels of octreotide. The resistance to octreotide therapy in these patients might be explained by the absence of somatostatin analogue receptors on their tumours. PMID- 1922593 TI - Megaloblastic anaemia in an elderly patient treated with triamterene. AB - The case is presented of an elderly woman in whom megaloblastic anaemia due to folate deficiency was diagnosed. It is speculated that this disorder was induced by treatment with triamterene. PMID- 1922594 TI - Hereditary protein C deficiency and portal-vein thrombosis. AB - Inherited defects of the natural coagulation inhibitors predispose patients to thrombosis. These disorders have similar clinical presentations with a strong family history of thrombosis, episodes of recurrent venous thromboembolism, beginning in early adulthood. We report a case of upper gastrointestinal bleeding in a patient with portal hypertension due to portal-vein thrombosis secondary to hereditary protein C deficiency, an association that has seldom been reported. PMID- 1922595 TI - Colorectal carcinoma: an update. AB - During the last decade important advances have occurred in the fields of understanding genesis, molecular biology, detection of "precancerous data", intervention, and metastatic behaviour of colorectal cancer. An important step forward has been made in adjuvant therapy. Better understanding of 5-fluorouracil metabolism has led to advances in the treatment of metastatic colon cancer. In this review these recent developments as well as future directions are discussed. PMID- 1922596 TI - Continuous ambulatory peritoneal dialysis (CAPD) in patients with diabetic nephropathy. AB - A 3-centre study was done to analyse the results of 70 patients with end-stage renal disease caused by diabetic nephropathy and treated with CAPD. Fifty patients had insulin-dependent diabetes (mean age 42, mean duration of diabetes 24 yr); 20 had non-insulin-dependent diabetes (mean age 61, mean duration 15 yr). Total treatment time was 1563 months and ranged from one to 83 months (median 18). Patient survival was 86% at 1 yr and 33% at 4 yr. Technique survival was 87% and 63%. Cox's multiple hazard regression analysis showed that age above 45 yr (relative risk 2.2), systolic hypertension (2.6) and cardiac disease (2.2) at the start of CAPD were associated with shorter patient survival. Metabolic control was good. Haemoglobin rose during the first 3 months. Plasma creatinine concentration increased with time, probably due to the loss of residual renal function. HbA1c levels were in the normal range for 60% of the patients. Mean hospital stay was 42 days per year, 26 as a consequence of vascular complications and 16 due to peritonitis and catheter-related problems. We conclude that CAPD is a good renal replacement modality for patients with diabetic renal failure. The patient survival is dependent on age, systolic hypertension and cardiac disease at the start of CAPD. PMID- 1922597 TI - More objective diagnoses of venous thromboembolism? AB - The clinical diagnosis of deep venous thrombosis is non-specific, i.e. suffers from a large number of false-positive diagnoses. Therefore, the use of objective tests is emphasized. We have investigated retrospectively the increase, if any, in the use of objective tests over a three year period in the Leiden area (1986 1989). We found that the percentage of patients on whom objective tests were used was more than doubled, from 21% to 55%; this increase was accompanied by a 29% decrease in the incidence of venous thromboembolic disease. These opposing trends are to be expected if more objective tests are used. PMID- 1922598 TI - Infected aneurysm of the abdominal aorta due to Listeria monocytogenes. AB - A 79-yr-old man was known for a year with a deteriorating clinical condition, vague abdominal complaints and an elevated erythrocyte sedimentation rate; he was afebrile. Extensive evaluation revealed no cause for his progressive disease. Eventually an infected aneurysm of the abdominal aorta was diagnosed, from which Listeria monocytogenes was cultured. After resection of the aneurysm the patient recovered initially very well. Regrettably, therapy-resistant chylous ascites developed, and the patient died due to surgical complications following a second laparotomy. Infected aortic aneurysms can present as an insidious disease, which may have catastrophic consequences if undiagnosed. A high index of suspicion is required to make a correct diagnosis. L. monocytogenes is an emerging, food-borne pathogen that can cause a wide spectrum of human diseases. PMID- 1922599 TI - Portal hypertension and intrahepatic cholestasis in hepatic amyloidosis. AB - Despite the fact that hepatic involvement is frequently seen in systemic amyloidosis, major clinical symptoms or impaired hepatic functional capacity are rare. We describe a patient with primary hepatic amyloidosis, severe intrahepatic cholestasis and portal hypertension, a combination previously reported only three times in the literature. In case of an unexplained intrahepatic cholestasis or portal hypertension the possibility of amyloidosis should be considered and a Congo red staining should be performed. PMID- 1922600 TI - "Spontaneous" catheter fracture and embolization of a totally implanted venous access port. AB - A case of "spontaneous" fracture of the catheter of a totally implanted venous access device is reported. The distal part of the catheter migrated into a pulmonary artery branch and could not be retrieved. The cause and consequences of this rare complication are discussed. It is emphasized that the integrity of a totally implanted venous access device should be ascertained before cytostatic agents are administered. PMID- 1922601 TI - Hydrocarbons and renal failure. PMID- 1922602 TI - Medium- and long-term prognosis of patients with acute poststreptococcal glomerulonephritis. AB - The prognosis of acute poststreptococcal glomerulonephritis (APSGN) is still a matter of considerable debate. In an attempt to elucidate this controversy, the medium-term prognosis was evaluated in 40 patients 5-9 years after the onset of the disease, and the long-term prognosis in 88 patients 10-17 years after the onset of the disease. All were sporadic cases. In the medium-term follow-up study, abnormalities were revealed in 5.0% (2/40) of the patients. Hypertension and proteinuria were the only abnormalities detected. In the long-term follow-up study, abnormalities were revealed in 6.8% (6/88) of the patients. Hypertension was found in 3.4, proteinuria in 2.3, and microhaematuria in 2.3% of the patients. In both studies, all patients had normal creatinine clearance. We conclude that the medium- and long-term outcome of patients with APSGN is excellent. PMID- 1922603 TI - Effects of recombinant human erythropoietin and correction of anemia on platelet function in hemodialysis patients. AB - To clarify the effects of correction of anemia with recombinant human erythropoietin (r-HuEPO) on the hemostatic defects in uremia, hemostatic parameters were examined in 18 hemodialysis patients with renal anemia. Anemia improved significantly 12 weeks after r-HuEPO therapy (stage II) compared to pretreatment (stage I) and 6 weeks discontinuation (stage III) periods. Platelet count did not change among the three stages, however, mean platelet volume increased significantly at stage II in comparison with stage I. Ivy bleeding time (BT) significantly shortened at stage II and prolonged again at stage III. Although there were no significant changes in platelet aggregation, plasma TxB2, 6-keto-PGF1 alpha, F.VIII:C and F.VIII:Ag levels throughout the study, platelet adhesion and von Willebrand factor (vWf):Ag significantly increased at stages II and III. Augmentations in these parameters were more remarkable in BT-shortened patients (n = 12) than in the BT-unchanged group. These results indicate that correction of anemia with r-HuEPO brought about improvement in uremic hemostatic defect via the increase in red cell volume and vWf:Ag, and new production of platelets, reflected by the improvement in platelet adhesion. PMID- 1922604 TI - Cerebral hemodynamic changes following treatment with erythropoietin. AB - Adverse hemorheologic effects induced by erythropoietin (EPO) treatment of renal anemia may pose a cerebrovascular risk. We therefore investigated the changes in cerebral perfusion, cerebral blood flow velocity (BFV) and neuropsychologic performance in 11 patients (mean age 37 years) receiving EPO. In response to EPO there was a significant (p less than 0.01) increase in hematocrit (35%), hemoglobin (43%) and whole-blood viscosity (50% at high and 90% at low shear rate). The initially increased blood flow velocity dropped significantly (p less than 0.05) and returned toward normal values in the middle cerebral arteries and the basilar artery (22 and 19% decrease, respectively). Global cerebral blood flow (CBF) decreased by 10% (not significant). The score of the Wechsler Adult Intelligence Scale digit symbol test improved significantly (p less than 0.01) after EPO treatment. None of the patients developed cerebrovascular symptoms or side effects. We conclude that the hematologic and rheologic changes following EPO treatment cause CBF and BFV to return toward normal and improve neuropsychologic performance in patients with end-stage renal disease. PMID- 1922605 TI - Proliferative response of T lymphocytes to mitogenic lectins in essential hypertension. AB - Several studies in human and experimental models indicate the existence of a partial relationship between essential hypertension (EH) and the immune system. In this study, cellular immune functions were investigated in 13 patients with untreated and uncomplicated essential hypertension (EHP) and in 10 of their offspring (EHO) and compared to 13 age- and sex-matched normotensive controls (NC) and 10 of their offspring (NCO). The total number of T cells and T cell subsets were similar in all groups examined. In the EHP, basal lymphocyte transformation without lectins was significantly lower (1,126 +/- 261 cpm of [3H] thymidine uptake) than in the NC (3,223 +/- 736, p less than 0.01); the response to both phytohemagglutinin (PHA) and concanavalin A (ConA) revealed reduced [3H] thymidine uptake as compared with NC (21,890 +/- 5,432 compared to 64,574 +/- 9,723 for PHA and 10,488 +/- 2,621 compared to 37,334 +/- 8,148 for ConA, respectively, p less than 0.01). However, the ability to proliferate as a response to lectins was normal. This was leading to a normal stimulation index in both groups. In the EHO, non-significant decrease in basal transformation and reduced uptake with PHA (49,537 +/- 7,478) versus NCO (69,911 +/- 7,254) and NC (64,574 +/- 9,723) were found. These findings suggest that the proliferative response of T lymphocytes is partially suppressed in EH. PMID- 1922606 TI - Antiglomerular basement membrane nephritis induced by IgA1 antibodies. AB - A 62-year-old man was admitted for acute renal failure due to crescentic rapidly progressive glomerulonephritis. Kidney biopsy showed intense staining for IgA, IgA1 and C3 in a linear pattern along the glomerular basement membrane (GBM). Serologic tests for detecting anti-GBM antibodies were positive for IgA class and IgA1 subclass and negative for IgG and IgA2. Serum IgA anti-GBM antibodies appeared essentially in the polymeric form, an observation in agreement with recent studies demonstrating polymeric IgA response after parenteral immunization. There was no sign of pulmonary involvement. This patient is the first to present with an isolated nephritis due to anti-GBM antibodies restricted to the IgA class (IgA1 subclass). Routine tests for circulating anti-GBM antibodies should also include the IgA class. PMID- 1922607 TI - Confirmation of tonsillar anomalies in IgA nephropathy: a multicenter study. AB - Tonsillar abnormalities have previously been evidenced in IgA nephropathy (IgAN). We report the results of a systematic quantitative analysis of 303 tonsils obtained in 70 IgAN patients and 142 controls. IgG- and IgA-producing plasma cells, stained by immunofluorescence, were enumerated on serial sections of all samples. Both the percentage and number of IgA+ cells were significantly increased in IgAN patients. This anomaly was also observed in age- or sex-matched subgroups of patients. Performed on a large series of individuals this study confirms the dysregulation of IgA production the upper respiratory tract of IgAN patients. PMID- 1922608 TI - Relationship of intraglomerular coagulation and platelet aggregation to glomerular sclerosis. AB - In order to investigate the relationship between intraglomerular coagulation and glomerular sclerosis, the distribution of fibrin-related antigen (FRA) in glomeruli without extracapillary lesions was examined by immunoperoxidase microscopy in 80 patients with IgA nephropathy (IgA-N). A total of 302 glomeruli were examined, including 20 with global sclerosis, 31 with segmental sclerosis (SS glomeruli), and 251 nonsclerosed glomeruli. In the nonsclerotic areas of SS glomeruli, the deposition of FRA was significantly greater than in the nonsclerosed glomeruli. In the nonsclerosed glomeruli FRA was mainly found in the mesangium, while in the nonsclerotic areas of SS glomeruli FRA was not only present in the mesangium but also in the endothelium of the glomerular capillary loops. FRA-positive microclots were also often observed attached to the endothelium of the capillaries of the nonsclerotic areas of SS glomeruli. Cross linked FRA was also observed in the endothelium of the same capillaries using the monoclonal antibody DD3B6/22. Deposition of von Willebrand factor (vWF) was greater in the endothelium than in the mesangium in the same areas. Aggregated platelets adhering to the glomerular capillary walls in these areas were frequently detected using the monoclonal antibody P2. Such distribution of platelets and vWF showed that the endothelium of the nonsclerotic areas of SS glomeruli was more severely damaged than that of nonsclerosed glomeruli. These findings suggest that endothelial cell damage might activate the intraglomerular coagulation, which might be one of the factors in the development of global glomerular sclerosis. PMID- 1922609 TI - Captopril but not acebutolol, prazosin or indomethacin decreases postexercise proteinuria. AB - Strenuous physical exercise causes transient proteinuria and renal hemodynamic changes: decrease of renal blood flow and to a lesser extent of the glomerular filtration rate, and an increase of the filtration fraction. However, the mechanisms of these modifications are still poorly understood. In order to elucidate them we performed maximal exercise tests on 8 untrained healthy volunteers after inhibition of the renin-angiotensin system (RAS) by captopril, the sympathetic nervous system by a beta-blocking drug (acebutolol) or an alpha blocking drug (prazosin) and the prostaglandin system by indomethacin. Urinary albumin excretion was measured in every subject first at rest (AB) and then after exercise (AA) performed successively without and with blockade by each of theses drugs. AA-AB difference in the captopril test (12.04 +/- 6.11 micrograms/min) compared to that in the control test (68.91 +/- 25.18 micrograms/min) was significantly reduced (p less than 0.02). This difference remained unchanged after acebutolol (59.87 +/- 21.91 micrograms/min, p = 0.62), prazosin (35.23 +/- 27.80 micrograms/min, p = 0.21) and indomethacin (55.21 +/- 28.43 micrograms/min, p = 0.35). There was a negative correlation between the lowering of AA elevation and the rise in plasma renin activity in the captopril test (r = 0.64; p less than 0.03). Only acebutolol decreased systolic blood pressure significantly. These results suggest that the RAS plays a major role in postexercise proteinuria. We hypothesize that stimulation of this system induces an increase of efferent glomerular artery constriction and consequently of glomerular transcapillary pressure and the filtration fraction. Captopril seems able to prevent these hemodynamic changes. PMID- 1922610 TI - Recovery of decreased ability of peripheral-blood mononuclear cells from chronic renal failure to produce interleukin-1 alpha and beta after renal transplantation. AB - The ability of cultured peripheral-blood mononuclear cells (PBMC) to release interleukin-1 alpha and beta (IL-1 alpha, IL-1 beta) in response to concanavalin A (con A) was investigated in patients with chronic renal failure (CRF) and in renal transplant recipients. Mean IL-1 alpha level released by PBMC of healthy subjects (n = 42), CRF patients (n = 42), or transplants 2 months after operation (n = 69) was 152 +/- 103, 110 +/- 80, or 154 +/- 87 pg/5 x 10(5) cells/ml culture, respectively. IL-1 alpha release from PBMC of recipients 2 months after renal transplantation was significantly higher than that of CRF patients (p less than 0.05). Mean IL-1 beta level released by PBMC of healthy subjects (n = 34), CRF (n = 30), or transplants (n = 55) was 223 +/- 159, 135 +/- 129, or 276 +/- 155 pg/5 x 10(5) cells, respectively. Similar to IL-1 alpha, the level in CRF was significantly lower than that in healthy subjects (p less than 0.05). A time course study indicated that the ability of PBMC from transplants to release IL-1 alpha and beta promptly decreased following the operation, possibly owing to prednisolone and ciclosporin immunosuppressive therapy. However, after maintaining a low level for 2-3 weeks, IL-1 release from PBMC gradually increased thereafter. The results were consistent with known characteristics of decreased immunity in CRF states, and further suggested that the decreased ability of PBMC to release IL-1 alpha and beta in response to con A in CRF patients is recovered 2 months after renal transplantation. PMID- 1922611 TI - Small intestinal peptidases and disaccharidases in rats with acute uremia. AB - Acute uremia was induced in rats with temporary clamping of the left renal pedicle and contralateral nephrectomy. Jejunal peptidase activities (aminopeptidase N, dipeptidyl peptidase IV and aminopeptidase A), disaccharidase activities (maltase, sucrase, lactase and trehalase) and morphology were studied. A significant (p less than 0.05) increase in aminopeptidase N activity and a positive correlation between aminopeptidase N activity and serum urea was found in the uremic rats. The other peptidase activities showed a slight increase in the uremic rats. A shortening of the microvilli of the small intestinal epithelial cells in the uremic rats was seen by electron microscopy. The disaccharidase activities was unaltered. This study shows the presence of functional alterations in the small intestine in rats with acute uremia. The observations are also compatible with different regulation mechanisms for the brush border peptidases and disaccharidases. PMID- 1922612 TI - Renal tubular protein handling in experimental renal disease. AB - Competitive inhibition of renal tubular transport occurs between low- and high molecular-weight proteins following intravenous infusion, but this relationship is less clear following de novo glomerular or renal tubular injury. The present study evaluated renal lysozyme and albumin handling following renal tubular injury induced by both low- and high-dose mercuric chloride (0.5 and 2.0 mg/kg) and maleic acid (50 and 400 mg/kg), and following glomerular injury induced by puromycin aminonucleoside (5 mg/100 g) or Adriamycin (5 mg/kg). Subtle renal tubular injury induced only mild isolated albuminuria, while severe tubular injury caused dramatic lysozymuria and moderate albuminuria. However, increased filtration of albumin in these models of glomerular injury did not inhibit lysozyme transport. PMID- 1922613 TI - Mesothelial hyperplasia in response to peritoneal dialysis fluid: a morphometric study in the rat. AB - Five rats were given twice daily intraperitoneal injections of hypertonic dialysis fluid for 6 weeks. The structure of the hepatic peritoneum of this group was compared with that of a control group by applying morphometric techniques to transmission electron micrographs. The experimental group showed marked mesothelial hyperplasia with doubling of the number of cells and a significant increase in the length of intercellular junction per unit area of peritoneum. Since cell volumes in the two groups were similar, the increase in cell density in the experimental animals was the result of the cells assuming a more cuboidal shape. Experimental animals also showed an increase in the number of microvilli, pinocytotic vesicles and rough endoplasmic reticulum per unit area of peritoneum. Chronic exposure to dialysis fluid has profound effects on the number, shape and composition of peritoneal mesothelial cells in the rat. PMID- 1922614 TI - Kimura's disease and membranous nephropathy. AB - An interesting association of Kimura's disease and membranous nephropathy is reported in a 71-year-old Chinese patient, 40 years after emigrating to the UK from Hong Kong. Significant blood eosinophilia and a very high serum IgE level were detected, the latter with a moderate level of specificity to Candida albicans. Light microscopy of renal biopsy was unremarkable despite a proteinuria of nephrotic proportions; diffuse subepithelial dense deposits compatible with membranous nephropathy were identified on electron microscopy. The atopic nature of Kimura's disease is confirmed and C. albicans is suggested as a possible causative agent. PMID- 1922615 TI - Facial leontiasis ossea: a rare presentation of hyperparathyroidism secondary to chronic renal insufficiency. AB - The term renal osteodystrophy is often used in a generic sense to include skeletal disorders of patients with chronic renal failure due to secondary hyperparathyroidism. The prevalence of this condition among patients on hemodialysis is considerably high. However, extreme forms such as facial leontiasis ossea are very rare, only 2 well-characterized cases having been reported thus far in the literature. In the present article we report the case of a female patient who developed hyperparathyroidism secondary to end-stage renal disease which was manifested as facial leontiasis ossea and culminated in dysphagia and respiratory difficulties caused by excess bone tissue growth. PMID- 1922616 TI - A case of angiotropic large cell lymphoma manifesting nephrotic syndrome and treated successfully with combination chemotherapy. AB - A 52-year-old female had a nephrotic syndrome without neurological or dermatological manifestations. Renal biopsy revealed that glomeruli were filled with tumor cells which bore leukocyte common antigen and pan B cell marker. These cells occupied the capillary lumen and invaded into the mesangial area. Morphological alteration of endothelial cells and glomerular basement membrane were also noticed. The interstitium was well preserved. After five cycles of a combination chemotherapy, CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone), the second biopsy revealed that tumor cells disappeared from glomeruli showing mild sclerosis. Proteinuria became absent. This is the first report of an angiotropic large cell lymphoma manifesting a nephrotic syndrome and treated successfully by CHOP therapy. PMID- 1922617 TI - Immunoelectron microscopic localization of fibronectin and complement to 'dense bodies' in Bowman's capsule and the glomerular basement membrane in membranous nephropathy. AB - This study describes dense bodies seen in Bowman's capsule and the glomerular basement membrane in biopsies of membranous glomerulonephritis. Within these bodies, silver-enhanced immunogold labelling demonstrated the presence of fibronectin and the complement component C3b. These results suggests that dense bodies may play a role in opsonization and the immune process in membranous glomerulonephritis. PMID- 1922618 TI - There is no aluminum accumulation in the skin of end-stage renal failure patients. PMID- 1922619 TI - Persistent glomerular abnormalities following orthotopic liver transplantation. PMID- 1922620 TI - IgA nephropathy with rapidly progressive course after kidney transplantation. PMID- 1922621 TI - IgM nephropathy in a patient with Kimura's disease. PMID- 1922622 TI - Bactericidal activity of serum of a child with focal proliferative glomerulonephritis. PMID- 1922623 TI - Is administration of vitamin D metabolite needed for the treatment of secondary hyperparathyroidism at the predialytic stage? PMID- 1922624 TI - Bone lead and renal failure. PMID- 1922625 TI - Trace elements and hemodialysis. PMID- 1922626 TI - Increased dialysis efficiency in tidal peritoneal dialysis compared to intermittent peritoneal dialysis. PMID- 1922627 TI - Animal experiments with a new dura graft (polytetrafluorethylene)--results. AB - A comparative animal experiment study on rabbits was performed to test a synthetic dura (expanded polytetrafluorethylene = ePTFE = Gore-Tex Surgical Membrane). For the purpose of comparison with the ePTFE implanted in the left hemisphere, lyophilized natural dura (Lyodura) was used and removed from the subjects after two, eight and twelve weeks. There were no rejection reactions. The lyophilized dura showed pronounced environmental reaction, with cellular permeation and indications of revitalization. The ePTFE manifested only slight reaction and remained inert in an enclosing sheath of connective tissue. The biocompatibility and other properties, such as simple handling and resteriliziability, of ePTFE can thus be assessed as positive. PMID- 1922628 TI - Factor XIII concentrate for prevention of recurrent subarachnoid hemorrhage: results of a multicenter pilot study. The FISAH Study Group. AB - Rebleeding after aneurysmal subarachnoid hemorrhage (SAH) has been attributed to fibrinolysis of the blood clot surrounding a rupture aneurysm. Since stability of the clot is influenced by the action of coagulation factor XIII (F XIII), high levels of F XIII might be beneficial in preventing recurrent SAH without causing the severe side effects of synthetic antifibrinolytics. We performed an open multicenter pilot study with administration of 10 x 1250 units of F XIII concentrate during the first 15 days after spontaneous SAH. Of 111 patients who were entered within 72 hours after SAH, 48 (43%) were in grades I and II, 33 (30%) were in grade III, and 30 (27%) were in grades IV and V according to Hunt & Hess. Aneurysm rupture was proved in 76 patients (68%) and aneurysm surgery was performed in 50 patients (45%). Overall mortality at four weeks was 27%. There were 11 recurrent hemorrhages in 9 patients (10%), 7 of which were fatal. Cerebral infarction occurred in 22 patients (20%) and hydrocephalus in 8 (7%). No adverse effects of therapy were noted. We conclude that F XIII therapy is a safe and promising new therapeutic approach in the management of SAH. It is currently being investigated in a large prospective, randomized, double-blind, placebo controlled trial. PMID- 1922629 TI - [Epithelial cyst of the central nervous system. A rare abnormality]. AB - A cystic process in the right frontal lobe of the brain in a man of 35 years of age, and an intramedullary cyst in the upper cervical spinal cord in a 29-year old woman, are described. In both cases, the wall of the cyst consisted of mucosal cells and cells having cilia pointing to the inside, located on a thin tissue layer, the structure of which resembled that of a meningioma. Central nervous cysts of this kind are usefully classified together with other, similar cysts (bronchogenic, ependymal and others) as "epithelial cysts". They must be differentiated from neoplastic tumours. Analysis of the cystic contents can prove helpful. PMID- 1922630 TI - Subependymoma of the septum pellucidum presenting as subarachnoid hemorrhage. PMID- 1922631 TI - Spinal intradural arachnoid cysts. AB - Three patients with indural spinal arachnoid cysts presented with back or neck pain of several months' duration. They gradually developed weakness and difficulty in walking followed by rapid deterioration with signs of spinal cord or nerve root compression. Radiological studies showed a posteriorly located mass in the cervical, dorsal and lumbar region; one cyst filled with contrast medium and the diagnosis of the others was made at operation. Surgery resulted in full recovery of two patients and partial recovery of the third. PMID- 1922632 TI - [Comment on the contribution by A. Aschoff et al., Neurochirurgia 32 (1989) 10 15: Safe placement of atrial shunt catheters using intracardial ECG]. PMID- 1922633 TI - [A better understanding of clinical pain. Experimental data on 3 animal models of pain]. AB - For a better understanding of clinical pain, several groups involved in the study of basic pain mechanisms have proposed the use of various experimental models close to clinical situations. These models are based either on neurogenic or inflammatory process. Data obtained with three of these models will be developed in the paper: rats rendered arthritic by Freund's adjuvant injection into the tail, rats with an intraplantar injection of carrageenin in one hindpaw, rats with a moderate ligature of one common sciatic nerve. The various pharmacological approaches revealed dramatic changes of the analgesic effects of morphine and other opioid substances, and a spectacular modification of the endogenous opioid reactivity. A further enhancement of the initial hyperalgesia was observed with high doses (1-3 mg/kg i.v.) of naloxone (known as an antagonist of morphine), contrasting with the paradoxical analgesia induced with the low dose (peaking up for 3 micrograms/kg i.v.). Electrophysiological studies emphasized dramatic changes of neuronal responsiveness in structures involved in the transmission of the nociceptive messages, from the periphery to the cortex. In each of these models electrophysiological data provide new insights on the physiopathological mechanisms of the related clinical pain. PMID- 1922634 TI - [Cervical carotid endarterectomy. Evaluation of a 12 years' experience (260 operations)]. AB - From 1978 to 1989, 235 patients were operated upon with 260 procedures for cervical carotid endarterectomy. The patients were classified according to the presence or absence of ischemic symptomatology, and for symptomatic patients, according to the reversibility or persistence of ischemic symptoms. So the selection of patients was: reversible ischemia 46%, stroke 29%, asymptomatic patients 25%. In the stroke group, no patient was operated on in emergency, the endarterectomy was performed after stabilization of the patients. Three subgroups were included in patients operated on for asymptomatic carotid stenosis: casual discovery 40%, treatment of the second carotid artery (previous endarterectomy for symptomatic controlateral carotid artery) 34%, and treatment of the second carotid artery (previous ECIC Bypass for controlateral occluded artery) 26%. All patients were operated upon after angiographic exploration (femoral catheterism in most cases), and after cerebral CT Scan. The surgical technique included general anesthesia, systematic shunting, endarterectomy after longitudinal arteriotomy, closure without patch. The operative microscope has been used since 1985. The operatives results were studied in terms of uneventful post-operative course (87.3%), reversible complications (8.1%) and long lasting complications (4.6%). The long lasting complications were of local origin (1.1%), of neurological origin (2.3%), of general origin (1.2%). Overall the operative results at 6 months were: return to previous clinical state 95.4%, neurological sequellae 1.5%, deaths 3.1%. In patients operated on for asymptomatic carotid stenosis the overall results were: previous clinical state 97%, death 3%. The legitimy of carotid endarterectomy procedure is discussed in view of some recent pertinent literature. PMID- 1922635 TI - [Esthesioneuroblastomas. Could a preoperative chemotherapy improve their prognosis?]. AB - The prognosis of malignant tumours of the olfactory epithelium of the nasal vault stays very poor. In the literature, the 5-year actuarial survival rate ranges between 50% and 65%; the 5-year recovery rate is 15% due to the high frequency of locoregional reoccurrences (60%) and metastasis (35-40%). Up to now chemotherapy was suggested as palliative treatment; but as Esthesioneuroblastomas (ETNB) appear to be sensitive to several chemotherapeutic agents (such as CDDP and 5 FU), we have decided to administer, from now on, to all patients harbouring an ETNB, an inductive chemotherapy whatever the staging and eventual diffusion of the tumour. The present paper presents our recent experience, dealing with such lesions: since 1984, 60 tumours of the ethmoid were treated in our department among which 7 ETNB (11.5%). We discuss our results concerning ETNB. PMID- 1922636 TI - [Idiopathic giant cell granulomas of the pituitary gland. Apropos of 2 cases]. AB - Two cases are reported of two women who had developed progressive hypopituitarism without visual disturbances. Pituitary tumors were evoked by radiological findings. The patients underwent surgical removal of invasive intrasellar tumor by transphenoidal route. Giant-cell granuloma was histologically demonstrated with negative special staining for tuberculosis acid-fast bacilli, bacteria and fungi. Secondary granuloma due to tuberculosis, brucellosis or neurosarcoidosis was ruled out by serological grounds. The prognosis was discusses through a follow-up of 7 years in the first case and 7 months in the second one. The appropriately documented 31 cases collected from the literature were compared with our two cases. PMID- 1922637 TI - [Epidural chordoma without bone involvement. A propos of a case in a child. Review of the literature]. AB - The authors report the case of a chordoma developed exclusively in the epidural space at the L1-L2 level in a 6 year old child. The tumor was easily removed in toto. No post-operative radiotherapy was given. The diagnosis of chordoma was based on the histological characteristics of the lesion and the results of immunohistological studies which were both typical of this lesion. This observation is exceptional because of the young age of the patient, the lumbar level of the tumor and, even more, the absence of any bone involvement. The 8 previously published cases of chordoma developed along the craniospinal axis but without bone involvement are reviewed and analysed: all were subdural; 7 were intracranial (6 prepontic, 1 suprasellar): only one was intraspinal. These lesions raise the problem of their diagnosis, of their treatment and of their embryogenesis. They could develop from ectopic notochordal remnants: the "ecchondrosis physaliphura". PMID- 1922638 TI - [Chondromyxoid fibroma of the cervical spine. Apropos of a case treated by partial vertebrectomy]. AB - A case of chondromyxoid fibroma revelated by cervicalgias and involving the right part of the 5th cervical vertebra is reported. This uncommon cartilaginous tumor is usually described in the metaphysis of long bones and appears very rare in the spine. If radiological aspects have been reported, the majors series do not describe a typical appearance of vertebral lesions; our patient is one of the first to have been evaluated by CT scan. Chondromyxoid fibromas are benign tumors, but recurrence is possible especially when treated by curettage alone. In our case, operated on two stages, the resection seemed sufficiently large and CT control on the 10th month did not show evidence of recurrence. Clinical and radiologic findings, and surgical management of these vertebral tumors are discussed. PMID- 1922639 TI - [Hydrocephalus caused by obstruction of the foramina of Luschka and Magendie in adults. Report of a case. Etiopathogenic discussion]. AB - The authors report the case of 30 years old patient presenting with an hydrocephalus responsible for high intracranial pressure and cerebellar ataxia. The fourth ventricle dilatation was predominant and there was no passage of the contrast media in the cisterna magna during ventriculography. For lack of neonatal antecedents and neurological pathology a congenital origin was evoked. The obstruction of the foramina of Luschka and Magendie with an hydraulic stability in the ventricles during the life before decompensation was likely. A ventriculo-peritoneal shunt, seemed to be the better treatment with regard to the permeability of the aqueduct. PMID- 1922640 TI - [Screwing the odontoid process. A functional operation]. AB - The authors describe a case of direct screw fixation of the odontoid process via an anterolateral retropharyngeal subhyoid pre-sternomastoid approach and discuss the indications for this operation. In this particular case, immobilization by a cervical collar or a halo vest was not chosen because of its constraining character and the risk of secondary displacement and pseudarthrosis. C1-C2 or occipitospinal arthrodesis, whether performed via a posterior, lateral or anterior approach, is difficult to perform and always leads to a functional handicap. The transoral approach does not allow direct screw fixation of the dens. Dens screwing via an anterior pre-sternomastoid subhyoid approach is the most logical and least disabling technique. The subhyoid approach is much simpler than the suprahyoid approach. This technique is used in fractures of the odontoid process with an ablique downward and backward fracture line, with or without arch fracture of C1, and allows screwing perpendicular to the fracture line. Considering the present results and the literature, the double screw fixation does not seem to be justified. PMID- 1922641 TI - [Endoscopic treatment of intracranial lesions. Apropos of 8 cases]. AB - The authors describe their initial experience involving endoscopic techniques used in the treatment of eight patients with varied brain lesions. Two tumours and a colloid cyst of the third ventricle, two paraventricular symptomatic cysts, one arachnoid cyst, one chronic intracerebral hematoma and one case of free catheter extraction in the lateral ventricle. The common characteristics of all these lesions were their liquid character and/or intraventricular location. Rigid endoscopes were used, with 9 and 6 mm work channels and independent aspiration and irrigation systems. The optic elbow makes direct visualization and adaptation to the TV monitor possible. The endoscope was manually directed at the lesion through a 12 mm burr hole in five cases and by means of a stereotactic frame in three cases. Biopsies were obtained in six cases. In three cases a communication between the cyst and the ventricular system or adjacent cisterns was established and in two cases vaporization of the lesion using a CO2 laser was performed. Tolerance to the endoscopic procedures was good in all cases. In the authors' opinion, endoscopic techniques constitute a low risk method, midway between stereotactic techniques and the microsurgical approach, and are especially indicated in the treatment of cystic brain lesions or those situated in or near the ventricular system. Their most notable advantages are: providing direct visualization of the lesion without interference from the instruments in the operating field; non-repercussion of the spatial changes derived from the liquid outlet and possibility of lesion coagulation and manipulation. Their disadvantages, related to the use of very long instruments and from a reduced work channel, must be overcome by specialized training. PMID- 1922642 TI - Incidence of the Guillain-Barre syndrome in Ferrara, northern Italy, 1981-1987. AB - The few incidence estimates on Guillain-Barre syndrome (GBS) in Italy indicate rates lower than the values provided by other previous non-Italian population based studies. The latter range from 0.6 to 1.9 cases per 100,000 population per year. To verify whether Italy may be considered a low-risk area for GBS we studied the incidence of the disease in Local Health Unit No. 31 (USL 31) of Ferrara, Northern Italy (mean population 180,701 inhabitants) for the years 1981 1987. The annual incidence rates were stable during this period with an average incidence of 1.26 cases per 100,000 population per year. No significant difference was found for urban or rural residence and there was no significant seasonal clustering. In 37.5% of the series an antecedent infection was recorded within 4 weeks before GBS onset. The survey seems to support the hypothesis of a homogeneous distribution of GBS in space and time and does not support the notion that GBS is less common in Italy than elsewhere. PMID- 1922643 TI - Parkinson's and motoneuron disease morbidity in the Twin Cities metropolitan area: 1979-1984. AB - To better characterize the morbidity from Parkinson's disease and motoneuron disease, we examined hospital discharge diagnosis data for all acute care facilities (except for the Veterans Administration Medical Center) in the Minneapolis-St. Paul area in each year from 1979 to 1984 for persons aged 30-74 years. For each person in whom the discharge diagnosis included either Parkinson's disease or motoneuron disease, the age, gender, and year of admission were recorded. Annual age-gender-specific and age-adjusted gender-specific hospital discharge diagnosis rates were calculated. For Parkinson's disease, for both, men and women, the age-adjusted hospital discharge diagnosis rate declined by 26-27%. Component age-specific data for Parkinson's disease showed more variable temporal changes. For motoneuron disease, no temporal changes were observed, although the number of observations was small. These data suggest that Parkinson's disease is declining in prevalence in the hospitalized population. The implications for motoneuron disease are less clear. Further studies in this area are needed. PMID- 1922644 TI - Progression of optic neuritis to multiple sclerosis: a prospective study in an Italian population. AB - We prospectively studied 40 patients with uncomplicated optic neuritis (ON) to determine the risk of subsequent multiple sclerosis (MS). All patients were followed for at least 12 years. Ten patients (25%) developed MS. Seven of these 10 patients developed MS within 2 years. Both sexes were at high risk if ON occurred between the ages of 21 and 40. There was an overall increased risk of MS with recurrent ON. The course of MS appeared to be fairly benign during the period of observation. PMID- 1922645 TI - Incidence and prognosis of brain abscess in a defined population: Olmsted County, Minnesota, 1935-1981. AB - The incidence of brain abscess was studied on all cases occurring in residents of Olmsted County, Minn., from 1935 through 1981. Thirty-eight cases (9 cases first diagnosed at autopsy) were identified and followed through the Rochester Olmsted County medical record-linkage system at the Mayo Clinic. The incidence rate was 1.3/100,000 person-years (PY), 1.9 in males and 0.6 in females. Incidence decreased from 2.7 in 1935-44 to 0.9 in 1965-81. Rates were higher in children 5 9 years old (2.4) and after age 60 (2.6 PY). An etiologic agent was identified in 29 cases (76%) with streptococci being the most frequently isolated. Case fatality ratio was 38% (11/29), stable over time. Concurrent bacterial meningitis was the strongest predictor of death. Neurologic sequelae were observed in 8 (44%) of the 18 surviving patients including epilepsy (5 cases), deafness and motor impairment. PMID- 1922646 TI - Psychologic and adaptational difficulties anteceding amyotrophic lateral sclerosis: Rochester, Minnesota, 1925-1987. AB - Comprehensive medical records of 45 amyotrophic lateral sclerosis (ALS) patients and 90 controls from the same community, matched by age, gender, and period of observation, were reviewed. Three (13%) of 23 men with ALS, 15 (33%) of 46 control men, 10 (45%) of 22 women with ALS, and 19 (43%) of 44 control women had antecedent psychologic or adaptational difficulties. The proportions of long standing or serious conditions were comparable in all four groups. However, no man in whom ALS developed had a record of mild antecedent difficulties alone, whereas 3 would have been expected (p = 0.024). PMID- 1922647 TI - Febrile seizures. AB - A door-to-door survey was carried out to screen a community of 14,010 people (Parsis living in colonies in Bombay, India) for possible neurological diseases. High school graduates, social workers, and a medical student administered a screening questionnaire that, in a pilot study, had a high sensitivity for identifying febrile seizures in children under the age of 14 years. Neurologists used defined diagnostic criteria to evaluate individuals positive on the screening survey. There were 1,581 children under the age of 14 years. Twenty eight children (19 boys, 9 girls) suffered from febrile seizures (17.7/1,000 population). The present prevalence study is the first from India and suggests that, contrary to expectation, the frequency of febrile seizures may be no different in developing and developed countries. PMID- 1922648 TI - Impact of demented patients on their family members and care-givers in Taiwan. AB - A standardized questionnaire was sent to family members or care-givers of 105 patients with dementia; 68 were returned. Eighty-eight percent of the patients were cared for at home by their spouses or adult children. The adverse impacts of dementia on patient family's economy, relations among family members, and social life are recognized. The majority of the subjects had only limited understanding of dementia. Having medical insurance helps the family in caring for the demented patients, emotionally and socially, but not financially. A better social welfare system, as well as health insurance, is recommended. PMID- 1922649 TI - A screening and alerting questionnaire for parkinsonism. AB - A self-administered eight-symptom questionnaire on parkinsonism was completed by 35 patients known to have parkinsonism and 88 controls independently selected by a local general practice. The presence of shaking and difficulty opening things/doing small buttons were the commonest positive responses among the cases (27/35). While a shuffling walk and difficulty turning in bed were the least frequent positive responses among the cases, they were also the two questions least likely to be positive in the control group. The question on shaking was the most discriminating between cases and controls. When the question on a shuffling walk was added, a positive answer to questions correctly identified 91% of cases and 92% of controls. These questions can form the basis of an alerting/screening questionnaire for parkinsonism and could be useful in screening smaller targeted populations such as a general practice list. PMID- 1922650 TI - High prevalence of herpes virus type 2 infection in Okinawa. PMID- 1922651 TI - [Heat-shock proteins: what implications in nephrology?]. PMID- 1922652 TI - [Urea kinetic model analysis in dialysis: from theory to practice]. AB - Urea kinetic modeling (UKM) has been originally proposed by F. Gotch and J. Sargent as a guide to optimize and individualize the dialysis prescription in uremic patients. In a recent report, the US National Cooperative Dialysis Study group, showed the power of this approach compared to conventional methods. It was also concluded that dialysis adequacy could be predicted with a high success rate by determining three parameters; uremia represented by the Urea Time Averaged Concentration, dialysis dose defined as KT/V ratio, and dietary protein intake calculated from the urea generation rate. In spite of its potential usefulness, UKM has not gained clinical acceptance among nephrologists since it appeared always complicated due to its mathematical formulation or cumbersome to be used routinely in dialyzed patients. In this paper the authors will bring the reader from basic concepts to practical use of UKM to guide dialysis strategy. Limits of validity and difficulty in using this approach are also discussed. It is concluded that UKM by using very simple and basic parameters is a practical, and very powerful tool for assessing the dialysis adequacy and nutritional status of dialyzed patients. Direct quantification from dialysate (or ultrafiltrate) collection appeared a simple and precise method which should avoided multiple blood sampling. PMID- 1922653 TI - [Auricular chondritis, malignant glomerulonephritis and pulmonary hemorrhage]. AB - Relapsing polychondritis is a rare connective tissue disorder characterized by inflammation of cartilagenous structures such as ears, nose, joints, trachea and larynx. Renal disease is unusual. A 41 years old man presented with auricular chondritis, subacute renal failure and lung hemorrhage. A renal biopsy disclosed a diffuse proliferative glomerulonephritis with extensive crescents. Immunofluorescent studies suggested a GNRP type III so called "non immunologic disease". He was treated by prednisone and plasmapheresis with rapid disappearance of pulmonary hemorrhages and good renal functional improvement. PMID- 1922654 TI - [Can cisplatin renal toxicity be prevented?]. AB - Cis diamminedichloroplatinum (CDDP) is a widely used anticancer agent particularly effective in the treatment of solid tumors. Dose limiting toxicity of CDDP was shown to be renal. Numerous methods to reduce this nephrotoxicity have been proposed. Hydration remains the best protection against acute CDDP nephrotoxicity in both the clinical and experimental setting. In man, no controlled studies have demonstrated the efficacy of furosemide and mannitol in the reduction of the CDDP renal toxicity. Studies have shown, however, that sodium thiosulfate offers some nephroprotection. To date, no controlled studies have demonstrated any benefit in the use of calcium channel blockers on CDDP renal toxicity in man. New drugs such as carboplatin have recently been introduced that theoretically have less renal toxicity, but evidence to support these claims are lacking. CDDP nephro protection remains a problem of current clinical interest and has yet not to be totally resolved. PMID- 1922655 TI - [Which transplantation strategies in primary hyperoxaluria type 1?]. AB - The following main conclusions concerning the transplantation strategies to be adopted in primary hyperoxaluria type 1 (PH1) were drawn from the data collected from 22 patients who received combined liver-kidney grafts and 2 patients who received isolated liver grafts in Europe from June 1984 to March 1990. In end stage renal failure due to PH1 liver-kidney transplantation yields better results than conventional renal transplantation. An isolated liver graft should be planned in patients with GFR between 25 and 60 ml/min/1.73 m2 whereas a combined liver-kidney graft is to be recommended as soon as the GFR falls below 25 ml/min/1.73 m2. Such patients should not be maintained on dialysis for more than a few months since they would unavoidably develop oxalosis with the risk of disabling lesions in the skeleton and cardiovascular system. Besides, oxalosis would be regularly followed by long-standing hyperoxaluria, with the risk of damage to the kidney graft, despite the correction of the enzyme deficit brought up by the liver graft. PMID- 1922656 TI - [Synthesis and role of cytokines in glomerular pathology]. PMID- 1922657 TI - Cytosolic free calcium concentrations in synaptosomes during histotoxic hypoxia. AB - Altered cytosolic free calcium concentrations ([Ca2+]i) accompany impaired brain metabolism and may mediate subsequent effects on brain function and cell death. The current experiments examined whether hypoxia-induced elevations in [Ca2+]i are from external or internal sources. In the absence of external calcium, neither KCl depolarization, histotoxic hypoxia (KCN), nor the combination changed [Ca2+]i. However, with external CaCl2 concentrations as small as 13 microM, KCl depolarization increased [Ca2+]i instantaneously while hypoxia gradually raised [Ca2+]i. The combination of KCN and KCl was additive. Increasing external calcium concentrations up to 2.6 mM exaggerated the effects of K+ and KCN on [Ca2+]i, but raising medium calcium to 5.2 mM did not further augment the rise. Diminishing the sodium in the media, which alters the activity and perhaps the direction of the Na/Ca exchanger, reduced the increase in [Ca2+]i due to hypoxia, but enhanced the KCl response. The changes in ATP following K+ depolarization, KCN or their combination in the presence of physiological calcium concentrations did not parallel alterations in [Ca2+]i, which suggests that diminished activity of the calcium dependent ATPase does not underlie the elevation in [Ca2+]i. Valinomycin, an ionophore which reduces the mitochondrial membrane potential, elevated [Ca2+]i and the effects were additive with K+ depolarization in a calcium dependent manner that paralleled the effects of hypoxia. Together these results suggest that hypoxia-induced elevations of synaptosomal [Ca2+]i are due to an inability of the synaptosome to buffer entering calcium. PMID- 1922658 TI - Biochemical quantitation and histochemical localization of glucose-6-phosphate dehydrogenase activity in the olfactory system of adult and aged rats. AB - The activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the hexose monophosphate shunt, was examined in olfactory epithelium, respiratory epithelium, olfactory bulb, and occipital cortex in Fisher 344 rats aged 4 and 24 months. Marked differences in this enzyme were found in olfactory compared to nonolfactory tissues. Olfactory epithelium and olfactory bulb have much greater glucose-6-phosphate dehydrogenase activity than respiratory epithelium and occipital cortex at both ages. Glucose-6-phosphate dehydrogenase remains fairly constant between adulthood and senescence in respiratory epithelium and occipital cortex. However, glucose-6-phosphate dehydrogenase activity decreases during the same time in both of the olfactory tissues examined. Previous studies of changes in this enzyme with aging have shown increases in enzyme activity in some brain regions, but never the decreases that we describe in olfactory tissues. Glucose-6 phosphate dehydrogenase histochemistry revealed intense staining of both the apical layer of olfactory epithelium and of Bowman's glands along with their ducts. Histochemistry of the olfactory bulb showed strongest staining in the nerve and glomerular layers of the bulb. The functional implications of these findings are discussed. PMID- 1922659 TI - Calcium-activated neutral protease activities in brain trauma. AB - This paper investigates the level of cytosolic and synaptosomal forms of calcium activated neutral protease activities in the normal brain and their changes following a freezing lesion in the rabbit. From 1 to 24 hours post lesion we observe a progressive disappearing of the enzyme activities from the cytosolic compartment and concurrently their increase in the membranal fraction. These changes are likely to be due to a rise in intracellular calcium concentration, a well documented consequence of many cellular insults. The specific role of the activation of calpain activities in the pathophysiology of trauma is discussed, an enhancement of excitotoxic mechanisms is proposed. PMID- 1922660 TI - Nicotinic receptor-elicited sodium flux in rat pheochromocytoma PC12 cells: effects of agonists, antagonists, and noncompetitive blockers. AB - Nicotinic agonists stimulate 22Na flux in rat pheochromocytoma PC12 cells. The stimulatory effect of carbamylcholine is maximal at 1 mM, while the stimulatory effect of nicotine and anatoxin maximize at the same level at 100 microM and 10 microM, respectively. The tertiary amines arecolone and isoarecolone have no effect on flux at 100 microM, while the methiodides at 100 microM stimulate flux to an extent similar to 1 mM carbamylcholine. Dihydro and alcohol analogues of isoarecolone methiodide have markedly smaller effects on flux. A preincubation for 2 to 20 min with carbamylcholine (2 mM), nicotine (300 microM), anatoxin (30 microM) or isoarecolone methiodide (100 microM) causes marked desensitization to a subsequent carbamylcholine-elicited stimulation of flux. d-Tubocurarine, mecamylamine, hexamethonium, and chlorisondamine inhibit carbamylcholine-elicited flux with IC50 values of 1.0, 0.8, 43, and 0.020 microM, respectively. Atropine has no effect at 1 microM, but reduces the response to carbamylcholine by 50% at 8.6 microM, presumably as a noncompetitive blocker. Other noncompetitive blockers of nicotinic acetylcholine-receptors, such as histrionicotoxins, gephyrotoxin, pumiliotoxin C, phencyclidine, bupivacaine and piperocaine, inhibit carbamylcholine-elicited stimulation of 22Na flux with IC50 values from 0.3 to 1.8 microM. In contrast to d-tubocurarine, which inhibits carbamylcholine elicited desensitization, and mecamylamine, which has no apparent effect on desensitization, chlorisondamine and certain noncompetitive blockers appear to enhance desensitization. The effects of agonists, antagonists and noncompetitive blockers at the neuronal nicotinic acetylcholine receptor-channel of PC12 cells are compared to their effects on binding of [125I]alpha-bungarotoxin to agonist recognition sites and of [3H]perhydrohistrionicotoxin to noncompetitive blocker sites of the nicotinic acetylcholine receptor-channel of electric ray (Torpedo) electroplax membranes. There are marked differences in relative potencies for the two types of nicotinic acetylcholine receptor-channel. PMID- 1922661 TI - Depolarization and synaptosomal glutamine utilization. AB - Synaptosomes prepared by discontinuous Ficoll gradient centrifugation were either pre-incubated with glutamine or incubated with releasing agents in the presence of glutamine. Under both conditions, KCl and 4-aminopyridine (agents with specificity toward the calcium-dependent pool) produced elevated glutamate (but not GABA) release when glutamine was included. AMPA and veratridine produced the same glutamate release in the presence or absence of glutamine. These data support the hypothesis that glutamine utilization is involved in the release of glutamate from calcium-dependent pools. PMID- 1922662 TI - [Late results of alternate treatment of multiple sclerosis with encorton and decaris]. AB - A group of 18 patients with clinically definite multiple sclerosis were subjected to alternate treatment with Prednisone (Polfa) and Decaris (Richter). The results were compared with those in a control group of 18 cases treated exclusively with Prednisone during exacerbations of the disease. The results indicate that the alternate treatment has not any significant effect on the course of multiple sclerosis, evaluated by the Kurtzke disability scale. The alternate treatment with a mild immunosuppression Encorton and immunomodulation-Decaris (Levamisole) leads to significant decrease of relapses in comparison with the period before the treatment, as well as in comparison with the control group treated exclusively with Encorton in case of exacerbations. PMID- 1922663 TI - [Evaluation of the status of the stomatognathic system in patients with idiopathic headaches]. AB - The stomatognathic system was assessed in 114 subjects with various types of idiopathic headaches. Stomatognathic system dysfunctions were recognized most frequently in patients with atypical facial pain and headache, and with mixed headache. Much less frequently these dysfunctions were present in patients with migraine or cluster headaches. The obtained results suggest that stomatognathic system dysfunctions should be considered in the pathogenesis of certain headaches. PMID- 1922664 TI - [Etiology, occurrence and types of the internal carotid artery loop]. AB - Internal carotid loop was studied in 99 patients out of 1638 cases subjected to angiography. The presence of a loop was arbitrarily accepted when in the tortuous part of the artery one of its segments was situated below the preceding segment. For the spatial analysis of the tortuous part of the artery and its image in the plane of the radiogram a model was used simulating various variants of the course of the internal carotid artery. On the ground of the analysis of the spatial configuration of the arterial loops and the variability of the loop model in the plane of the radiogram six types of the loop were isolated. The loops were found in 9.2% of patients with bilateral angiography and 5.7% of those with unilateral angiography. In adults the loop was present in 5.4% of cases, and in children in 8.9% (statistically significant difference p less than 0.05). It is assumed that the loop in children is a congenital anomaly, while in adulthood besides the congenital etiology an acquired form of the loop is to be taken into account. PMID- 1922665 TI - [Subarachnoid hemorrhage from ruptured intracranial aneurysm and surgical procedures as a cause of neuropsychological disorders]. AB - The results of preoperative and postoperative examinations in 30 patients operated on for ruptured intracranial aneurysm are reported. The examinations included neuropsychological, neurological and EEG assessment. The agreements and divergencies in the assessment of the condition of the patients by these methods were analysed suggesting the necessity of consideration of psychological disturbances as a consequence of the disease in the general evaluation of the therapeutic results in such cases. PMID- 1922666 TI - [Comparative evaluation of using autologous cable transplants and the classical microsurgical method of nerve anastomosis]. AB - Using the microsurgical technique in 19 cases the union of 27 injured nerves was done within 24 hours after the injury, with simultaneous suture of the remaining anatomical structures of the extremity. In cases in which after adequate resection the gap in the nerve was not exceeding 2 cm the classical end-to-end suture was done (12 cases) in the remaining 15 cases autogenous bridging (cable) grafts were used. In cases with cable grafts very good or good results were obtained, in the cases of end-to-end suture a poor result was noted in one case. It was found that one-step reconstruction of all severed anatomical structures of the extremity (tendons, vessels, nerves) was undertaken during the first surgical intervention by microsurgical techniques was the best method, and autogenous cable grafts were superior to end-to-end anastomosis in primary reconstruction of damaged peripheral nerves. PMID- 1922667 TI - [Our experience with using nimodipine in the treatment of ischemic complications after subarachnoid hemorrhage]. AB - On the basis of 50 patients treated for subarachnoid haemorrhage the authors report own experiences with the use of Nimotop for control of vasospasm caused by cerebral ischemia. All these patients were in grades III and IV of the Hunt-Hess scale. The studied patients with vasospasm and cerebral ischaemia were compared with patients similarly in grades III IV of this scale who were not given Nimotop. The analysis showed that patients treated with Nimotop were operated on earlier and had less evident neurological defect on discharge from the hospital. PMID- 1922668 TI - [Conservative treatment of post-traumatic intracerebral hematoma]. AB - Out of 184 patients with posttraumatic intracerebral haematomas 52 were treated conservatively. For this treatment patients were qualified with good consciousness level, in the range of 13-15 GCS score. Presence of massive neurological deficit was not an indication to treatment. Patients with haematomas in the central zone, with multiple haematomas or with contraindications to operation were treated conservatively. Eight patients died (15%), in 2 of them severe brain trauma with multiple haematomas were the cause of death, in 1 case primary brainstem trauma was present, one patient had deeply situated haematoma of the thalamus and ventricular system, and in 4 cases death was due to non cerebral causes. The size of the haematoma in CT scan was not decisive for the choice of the treatment. Nearly in all cases compression of the ventricular system was present, but in only some cases the ventricles were shifted. In repeated CT scans resorption of the haematomas was observed. Twenty patients were discharged home in good general condition without serious neurological deficit. Twenty-four patients were treated later on in other hospital departments. Later outpatient control examinations showed that even serious neurological deficits regressed in most cases. The main symptoms were those of the post-trauma syndrome. About 25% of patients had epileptic seizures after the treatment. The author believes that if the patient is conscious and his consciousness is not worsening conservative treatment of intracerebral haematomas may be undertaken with good effects, on condition, however, of the availability of immediate surgical intervention if the condition of the patient is deteriorating. PMID- 1922669 TI - [Ophthalmic artery branches examined by Doppler ultrasonography]. AB - Anomalies in the internal carotid artery which cause disturbances in blood flow dynamics in this artery affect also the blood flow in the ophthalmic artery and its branches. The blood flow in the ophthalmic arteries is assessed by USG-D examination with or without compression test. The test provides information on the nature and direction of the blood flow in the ophthalmic artery as well as source of collateral circulation. Good results in the ultrasonic assessment are obtained by using combined study of blood flow in the ophthalmic artery branches with the compression test as well as by direct study of the internal carotid artery. The above conclusion was reached in view of a high - agreement between the results of ultrasonography and contrast methods. PMID- 1922670 TI - [Diagnostic problems in a case of dissecting aneurysm of the abdominal aorta with subsequent myelomalacia]. AB - A man aged 51 developed signs of damage to the inferior part of the thoracic cord and lumbosacral cord due to a dissecting aneurysm of the abdominal aorta. The aneurysm was demonstrated by USG and CT investigations of the abdomen. PMID- 1922671 TI - [Coexistence of multiple sclerosis and myasthenia gravis]. AB - A young female is reported in whom multiple sclerosis and myasthenia gravis coexisted. The coexistence of multiple sclerosis with other autoimmune diseases and associations with histocompatibility antigens are discussed. PMID- 1922672 TI - [Trial use of the personal computer Atari ST for measuring intracranial pressure by the epidural method]. PMID- 1922673 TI - [Localization of the epileptogenic focus in a case of xantho- astrocytoma of the temporal lobe by brain mapping]. PMID- 1922674 TI - Role of testosterone in the regulation of tuberoinfundibular dopaminergic neurons in the male rat. AB - The effects of testosterone on the tuberoinfundibular dopamine (DA) neuronal activity was examined by determining the rate of DA synthesis-accumulation of 3,4 dihydroxyphenylalanine (DOPA) after administration of a decarboxylase inhibitor and the concentration of a DA metabolite,--3,4-dihydroxyphenylacetic acid (DOPAC) -in the median eminence in the male rat. Within 1 week after orchidectomy, there was an increase in the accumulation of DOPA and the concentration of DOPAC in the median eminence, but there was no change in the concentration of DA. Conversely, 1 day after testosterone administration to orchidectomized rats, the elevated DOPAC concentrations in the median eminence returned to levels comparable to those in gonadally intact rats. Neither orchidectomy nor testosterone replacement had any effect on plasma prolactin concentrations, but inhibition of prolactin secretion following administration of the DA agonist bromocriptine blocked the increase in DOPA accumulation in the median eminence of orchidectomized rats; this latter effect was reversed by intracerebroventricular administration of prolactin. On the other hand, intracerebroventricular injection of prolactin caused a similar increase in the accumulation of DOPA in the median eminence of gonadally intact, orchidectomized, and testosterone-treated orchidectomized rats. Immobilization stress decreased the accumulation of DOPA and the concentration of DOPAC in the median eminence of orchidectomized rats, but had no effect in intact or testosterone-treated orchidectomized rats. These results indicate that testosterone inhibits the basal activity of tuberoinfundibular DA neurons and blocks the inhibitory effects of physical restraint on these neurons, but does not alter the ability of these neurons to respond to delayed activation by prolactin. PMID- 1922675 TI - Subcellular distribution of corticotropin-releasing-factor-like immunoreactivity in rat central nervous system. AB - Corticotropin-releasing-factor-like immunoreactivity (CRF-LI) was measured in a number of subcellular fractions from rat brain using a highly sensitive and specific radioimmunoassay. CRF-LI was highly enriched in the crude synaptosomal/mitochondrial fraction (P2) relative to the homogenate, P1, S1, and S2 fractions. Separation of the P2 fraction into synaptosomal, myelin, and mitochondria-enriched subfractions on a rapid one-step sucrose gradient revealed that CRF-LI was present at higher concentration in the synaptosomal fraction than in the mitochondrial and myelin fractions. The distribution of CRF-LI paralleled that of synapsin, a synaptic vesicle marker phosphoprotein, but not that of pyruvate dehydrogenase, a mitochondrial phosphoprotein. These results are consistent with a nerve terminal localization of CRF and a potential role for this peptide as a central nervous system neurotransmitter. PMID- 1922676 TI - Effect of head-up tilt on vasopressin secretion and arterial pressure in anesthetized rats. AB - The effect of 45 or 60 degrees head-up tilt on plasma arginine vasopressin (AVP) concentration, mean arterial pressure, and heart rate was studied in inactin anesthetized rats. In all rats, there was a fall in blood pressure that was maximal within about 20-40 s and then returned toward normal. After 45 degrees head-up tilt for 30 min, AVP was increased from 7.0 +/- 1.7 to 21.0 +/- 5.9 pg/ml. Sixty-degree head-up tilt increased AVP at 5, 15, and 30 min, respectively, from 10.6 +/- 2.9 to 22.1 +/- 4.8 pg/ml, from 10.6 +/- 2.5 to 28.5 +/- 5.3, and from 16.1 +/- 4.7 to 62.6 +/- 10.3 pg/ml. After bilateral cervical vagotomy, 60 degrees head-up tilt for 30 min increased AVP, but the change was significantly reduced compared to intact animals. Bilateral sinoaortic denervation increased basal values of AVP, and there was no further increase during tilt. Bilateral electrolytic lesions of the hypothalamic paraventricular nuclei caused only a moderate reduction in the AVP response to tilt. When the effect of endogenous angiotensin II was antagonized by saralasin or its production was blocked by enalapril, the AVP response to tilt was reduced. The mean arterial pressure fell during the 1st min, but recovered rapidly when rats treated with a V1 vasopressin receptor antagonist were tilted. The data indicate that head-up tilt increases AVP secretion in anesthetized rats, that the response is mediated by the vagus and particularly by the arterial baroreceptors, and that circulating angiotensin II contributes to the response. However, the increased circulating AVP is not necessary for the maintenance of arterial pressure. PMID- 1922677 TI - Effects of active immunization against gonadotrophin-releasing hormone on the concentrations of noradrenaline, dopamine, 5-hydroxytryptamine and some of their metabolites in the brain and sexual organs of male rats. AB - This is an investigation of the effects of active immunization against gonadotrophin-releasing hormone (GnRH) conjugated to keyhole limpet hemocyanin on brain and male sexual organ concentration of catecholamines and 5 hydroxytryptamine. The treatment induces antibodies against GnRH with consequent interference with reproductive function as indicated by the attendant decrease in serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone. Rat striatal and mesolimbic dopamine levels were moderately increased by this treatment but no changes were observed in the hypothalamus. GnRH immunization also increased brain 5-hydroxytryptamine concentrations as observed in the hypothalamus, olfactory tubercles and striatum. In the male accessory sexual organs, immunity against GnRH alters the density of noradrenergic concentration. The changes occurred in opposite directions in the different regions investigated; increases in noradrenaline were observed in the prostate, with a reduction being detected in the epididymus and no changes were observed in the vas deferens or the seminal vesicles. 5-Hydroxytryptamine levels increased in the vas deferens but no effects were observed in the epididymus, prostate or seminal vesicle. It is concluded that GnRH immunization with the consequent reductions in circulating FSH, LH and testosterone are associated with changes in neurotransmitter concentration both in the brain and in some of the accessory sexual organs in the male rat. PMID- 1922678 TI - Effects of daily afternoon melatonin administration on monoamine accumulation in median eminence and striatum of ovariectomized hamsters receiving pargyline. AB - The effects of daily afternoon melatonin injections on the accumulation of monoamines were studied in extracts of median eminence, and of caudate nucleus, of intact and ovariectomized Syrian hamsters which were administered pargyline 2 h prior to sacrifice. Although no significant effect of melatonin administration on the serotonin (5HT) accumulation after pargyline could be detected, significantly increased amounts of 5HT and of the 5HT metabolite, 5-hydroxyindole acetic acid, were detected in median eminence and in caudate nucleus of melatonin injected hamsters not treated with pargyline. In both median eminence and in posterior pituitary, dopamine (DA) concentrations were significantly reduced by melatonin administration. In the median eminence of intact hamsters, the accumulation of DA after pargyline was reduced to 22% of controls by melatonin injections; in ovariectomized hamsters, the accumulation of DA was reduced to 9% of controls by melatonin injections. The accumulation of norepinephrine after pargyline was significantly reduced by melatonin administration only in ovariectomized hamsters. No significant inhibitory effects of melatonin injections could be detected on DA accumulation in caudate nucleus. These data suggest that melatonin injections result in substantial inhibition of daytime DA synthesis in median eminence independently of its effects on gonadal steroids. Paradoxically, melatonin-induced inhibition of median eminence DA activity occurred concomitantly with suppression of pituitary and plasma prolactin (PRL). We conclude that daily afternoon melatonin injections inhibit PRL secretion and interfere with cycles of LH in spite of decreased DA activity in the median eminence. PMID- 1922679 TI - Regulated production and secretion of immunoreactive neuropeptide Y by aggregating fetal brain cells in cultures. AB - The aim of this study was to establish a culture system of fetal brain cells that could serve as a model for the study of the developmental regulation of the neuropeptide Y (NPY) neuron. Single cell suspensions were prepared from the hypothalamic-olfactory tubercle region of 18-day-old rat fetuses, and aggregates were formed by incubation in serum-free medium under constant rotation. Aggregate formation was complete within 24-48 h, and cultures were maintained for up to 23 days. The content of immunoreactive (IR) NPY in the medium and in the aggregates increased progressively with time in culture and at each time point, the medium contained 5- to 10-fold more NPY-IR. A 48-hour exposure to forskolin resulted in a 2-fold increase in the accumulation of NPY-IR in the aggregates and in the medium, indicating that both production and secretion of NPY are regulated by the cAMP intracellular pathway. Sephadex gel filtration revealed the presence of proNPY- and NPY-size substances. The ratio of NPY- to proNPY-size substances increased progressively with age of the aggregates as well as in tissues obtained from perinatal rats of comparable age. Thus, production and secretion of NPY-IR in the cultured aggregates are regulated processes and hence, this culture system can serve as a model to study regulatory processes in the developing NPY neuron. PMID- 1922680 TI - Suckling-induced changes of vasoactive intestinal peptide concentrations in hypothalamic areas implicated in the control of prolactin release. AB - The present study was designed to investigate whether the vasoactive intestinal peptide (VIP) concentration in hypothalamic nuclei, dorsal raphe nucleus (DR) and pituitary lobes of lactating rats changes in physiological situations when prolactin (PRL) secretion is stimulated (suckling) or inhibited (pup separation). In addition VIP levels in blood plasma were determined in both situations. Acute suckling induced changes in VIP concentration only in the rostral part of the anterior hypothalamic (rAHN) and the paraventricular (PVN) nuclei of all the brain areas examined. VIP concentration in the rAHN increased at 5 min from 3.52 +/- 0.30 (mean +/- SEM) to 8.67 +/- 1.91 ng/mg protein (p less than 0.05) but fell to baseline values after 30 min suckling (p less than 0.05; 5 vs. 30 min). Although changes in VIP concentration in the suprachiasmatic nucleus (SCN) did not attain statistical significance, they followed the same trends as the changes of VIP in the rAHN. The opposite pattern of changes was observed in the PVN with a decrease in VIP concentration following 5 min suckling (p less than 0.01). At 30 min the VIP values showed a trend towards 0-min values. Pup removal did not affect VIP concentrations in the rAHN, PVN, SCN, median eminence, supraoptic nucleus and DR. VIP values were not detectable in the arcuate nucleus in any of the experimental situations examined. Lactation increased VIP concentration only in the rAHN and PVN when lactating rats with their pups were compared with virgin female diestrous rats. VIP concentration in the anterior lobe of the pituitary from lactating rats did not change with pup separation or suckling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922681 TI - Release of dopamine is reduced by diazepam more in the nucleus accumbens than in the caudate nucleus of conscious rats. AB - The effects of 1-20 mg/kg diazepam were studied on the extracellular concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and striatum of conscious rats, using intracerebral microdialysis. Five, but not 1 mg/kg diazepam significantly reduced extracellular DA, DOPAC and HVA in the nucleus accumbens. Twenty mg/kg diazepam significantly reduced extracellular DA, DOPAC and HVA in the striatum. A significant effect on striatal DOPAC, but not on DA and HVA, was seen with 10 mg/kg diazepam, while no changes were found with 5 mg/kg diazepam. The results suggest that diazepam reduces the release and metabolism of DA in the nucleus accumbens more than in the striatum. PMID- 1922682 TI - Spatial and temporal patterning distinguishes the locomotor activating effects of dizocilpine and phencyclidine in rats. AB - A behavioral pattern monitor was used to assess the effects of dizocilpine (MK 801) and phencyclidine on the spatial and temporal patterns of locomotion and investigatory behavior in rats. The monitor provided both quantitative measures of crossovers, rearings and holepokes and qualitative measurement of the spatial and temporal patterns of locomotion. Dizocilpine (0.004-0.5 mg/kg) and phencyclidine (0.25-5.0 mg/kg) produced similar, dose-dependent increases in locomotor activity. At small doses, dizocilpine and phencyclidine increased investigatory holepokes, while at larger doses, both drugs significantly decreased the number of holepokes. Rearings were reduced similarly by the larger doses of each drug. Both dizocilpine and phencyclidine produced perseverative spatial patterns of locomotion, especially at larger doses. However, the locomotor patterns produced by these drugs were found to be dissimilar in spatial quality. After phencyclidine, animals frequently circled the perimeter of the monitor chamber or moved repetitively in horseshoe or figure-8 patterns. By contrast, rats given dizocilpine completed small rotations about either end of the chamber. Pretreatment with a small dose (0.02 mg/kg) of haloperidol, prior to either dizocilpine (0.5 mg/kg) or phencyclidine (5.0 mg/kg) had no effect on the increase in locomotor activity or the decreases in investigatory holepokes produced by the drugs. However, haloperidol altered the effects of phencyclidine on the spatial and temporal patterns of locomotion, suggesting that sigma receptors or other haloperidol-sensitive binding sites, may influence the quality but not the quantity of phencyclidine-induced hyperactivity. PMID- 1922683 TI - Effect of psychotropic agents on a model of absence epilepsy in rats. AB - The effect of different groups of psychotropic agents on the spontaneous absence like paroxysms in the ECoG of rats was studied in order to evaluate the specificity of the model for antiabsence drugs. Morphine-like analgesics increased the number of paroxysms, whereas this was depressed or the discharges were completely abolished by the following drugs: d-amphetamine, tricyclic antidepressants, centrally acting anticholinergics and L-DOPA, NMDA antagonists and memantine. Since the latter drugs have been reported to be effective in petit mal epilepsy, or the NMDA antagonists and memantine, have a potential anticonvulsant effect, the results are in favour of the usefulness of the model for antiabsence drugs. PMID- 1922684 TI - Attenuation of epileptogenesis by nonsteroidal anti-inflammatory drugs in the rat. AB - Subconvulsive doses (25 mg/kg) of pentylenetetrazol were administered at intervals of 4 days for 20 sessions, to induce kindling in conscious, free-moving rats, with chronically-implanted electrodes. This regimen induced an excitation of the CNS, which intensified over the 20 sessions. Periods of motor arrest, concurrent with bursts of electrocortical spike-wave activity, increased to clonic convulsions, concurrent with bursts of spike activity. Separate groups of rats were pretreated over the twenty sessions with nonsteroidal anti-inflammatory drugs (NSAIDs). Pretreatment with paracetamol produced a dose-related reduction in pentylenetetrazol-induced seizure activity. Pretreatment with 20 mg/kg mefenamic acid attenuated, while 60 mg/kg dose potentiated, the pentylenetetrazol induced excitation. Pretreatment with 10 or 30 mg/kg ibuprofen had no significant effect, while 90 mg/kg was lethal, by itself, in 58% of the group. When all the groups received a single dose of pentylenetetrazol, three weeks after the twenty sessions, there were no significant differences between the groups in level of pentylenetetrazol-induced excitation, when compared to the control (saline pretreated) group. This suggests that the effective NSAIDs had influenced the manifestation of, but not development of, epileptogenesis over the 20 sessions. PMID- 1922685 TI - The effect of soluflazine on sleep in rats. AB - Soluflazine, a specific adenosine transport inhibitor, was intracerebroventricularly administered to rats in a dose range of 10, 25, and 50 nmoles. At a dose of 50 nmoles, soluflazine decreased waking and increased sleep during the first hour of EEG recording. Our previous work has shown that chronic intracerebroventricular administration of soluflazine to rats decreased radioligand binding to adenosine A1 and A2 receptors in specific brain regions. The present data show that administration of an adenosine transport inhibitor to rats produces a transient hypnotic effect presumably through increases in synaptic adenosine levels. PMID- 1922686 TI - Age-related toxicity in prefrontal cortex and caudate-putamen complex of gerbils (Meriones unguiculatus) after a single dose of methamphetamine. AB - Single, intermediate to large doses (6-60 mg/kg) of methamphetamine were applied to study the acute neurotoxic effects in developing male gerbils (up to 24 months). A sensitive silver-staining method was used to analyze the toxicity of methamphetamine by light and electron-microscopy. It was shown that treatment with the drug degraded synaptic components, as well as a small population of neurones in the caudate-putamen complex accompanied by accumulation of lysosomes in fibers and axon terminals. In juveniles, methamphetamine in doses of 25-60 mg/kg, resulted in accumulation of lysosomes, selectively in the prefrontal cortex. In young adults, only about half of these doses were sufficient to produce consistent and/or additional effects in the caudate-putamen complex. When the gerbils grew older than 8 months, treatment with drug led to accumulation of lysosomes, exclusively in the caudate-putamen, with acute doses ranging from 6 to 12 mg/kg. Acute neurotoxicity with methamphetamine has thus been induced by doses, which hitherto have been claimed to produce behavioural sensitization. Since dopamine (DA) seems the most likely transmitter to be affected, age-related differences in methamphetamine-induced neurotoxicity are discussed in relation to the background of developing DA-response systems, which are still changing in pattern during ageing. PMID- 1922687 TI - Acute and chronic studies with the anticholinesterase Huperzine A: effect on central nervous system cholinergic parameters. AB - High affinity choline transport, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were assessed in rats after acute and chronic administration of the AChE inhibitor Huperzine A. Acute treatment: Forty-five min after a single injection of Huperzine A (0.5 mg/kg i.p.) the activity of AChE was significantly decreased by 15-30% in hippocampus, striatum and septum. The activity of ChAT was not altered. In the hippocampus high affinity choline transport was attenuated by 25%, whereas no effect in the striatum was observed. After 90 min, both inhibition of AChE and attenuation of high affinity choline transport had returned to control values. A dose of 0.1 mg/kg (i.p.) did not produce significant effects. Similar results were obtained with physostigmine (0.25 mg/kg), although the duration of inhibition of AChE was shorter than that with Huperzine A. Chronic treatment: After 5 days (twice a day), at 0.5 mg/kg, the activity of AChE was significantly reduced by 20-30% in every region of the brain studied. High affinity choline transport in the hippocampus was reduced by 28%, 45 min after the last injection, but in the striatum there was no effect. The activity of ChAT was not affected in any region of the brain studied. Thus, acute or chronic treatment with Huperzine A: did not alter ChAT; reduced high affinity choline transport in the hippocampus in a transient manner; and had a longer duration of action as an AChE inhibitor than physostigmine. Moreover, tolerance to low-toxicity doses of Huperzine A was minimal, contrary to what has been observed with other inhibitors of AChE. PMID- 1922688 TI - Adenosine receptor-coupled adenylate cyclase in the caudate nucleus of the rat brain. AB - 5'-(N-Ethylcarboxamido)adenosine (NECA) and N6-[(R)-(phenylisopropyl)]adenosine (PIA) were incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen tissue of the rat, in order to examine the effect of kainic acid and a 6-hydroxydopamine-induced lesion on adenosine receptor coupled adenylate cyclase in vitro. There was an enhancement of formation of cyclic AMP induced by NECA, that was mediated by A2 adenosine receptors. Phenylisopropyl adenosine also stimulated adenylate cyclase in the striatum, with a maximum increase at 0.1 mM. At smaller concentrations, PIA inhibited the basal activity, which was previously described to be an effect mediated by A1 adenosine receptors. In caudate-putamen tissue from rats receiving a unilateral lesion, induced with kainic acid, basal and maximally NECA- and PIA-stimulated activity of adenylate cyclase was decreased. The maximum stimulatory effects of both substances were also significantly decreased, whereas no change of the inhibitory effect of PIA was observed. After unilateral lesion induced with 6-OHDA, basal and maximally NECA- and PIA-activated adenylate cyclase was increased; however, no inhibitory effect of PIA was seen. These results suggest that A2 adenosine receptor-coupled adenylate cyclase was located on neurones intrinsic to the neostriatum and probably postsynaptic to the dopaminergic input. The A1 adenosine receptors seem to be associated with the nigrostriatal pathway implying a presynaptic localization on dopaminergic afferents. In addition, since after both kainic acid and 6-OHDA-induced lesions, respectively, in caudate-putamen tissue of the contralateral side, PIA no longer inhibited the activity of adenylate cyclase, contralateral structures also appeared to be involved in the regulation of A1 adenosine receptors. PMID- 1922689 TI - High vulnerability of dentate granule cells to the neuropathological effects induced by intrahippocampal injection of tetanus toxin. AB - The behavioural and neuropathological effects of tetanus toxin, injected into the dentate gyrus, were studied in rats. The monolateral injection of a single dose (1000 mouse minimum lethal doses, MLDs; n = 14 rats) of tetanus toxin produced time-dependent behavioural stimulation. Wet-dog shakes and facial stereotypy were observed 3-4 days after the injection, culminating 4-5 days after treatment, in "limbic motor seizures". Ten days after injection, histological examination revealed death of dentate granule cells in the tetanus toxin-treated side but not in the contralateral, control side (treated with neutralized toxin). This effect was observed in all rats (n = 5) receiving tetanus toxin in the dentate gyrus and no damage was reported in other sectors (e.g. CA1 and CA3 pyramidal cell layers) of the hippocampus. Quantification of the neuronal damage yielded an approximately 70% reduction (P less than 0.01) in the number of granule cells in the toxin-injected dentate gyrus, compared with the control side. This was greater than that previously reported (30% reduction) in the CA1 pyramidal cell layer of rats receiving the same dose of toxin, into the regio superior of the hippocampus. In conclusion, the present experiments have shown that the focal injection of tetanus toxin into the dentate gyrus produced behavioural excitation and selective death of dentate granule cells. PMID- 1922690 TI - Inhibition of rat brain monoamine oxidase activity by cerebral anti-ischemic agent, ifenprodil. AB - Ifenprodil, which is clinically used as a cerebral vasodilator, inhibited rat brain type A (MAO-A) and type B (MAO-B) monoamine oxidase activity. It did not, however, affect rat lung semicarbazide-sensitive amine oxidase. The degree of inhibition of either form of MAO was not changed by 30 min preincubation of the enzyme preparations at 37 degrees C with ifenprodil. Modes of inhibition of MAO-A and MAO-B by ifenprodil were competitive towards oxidation of their respective substrates, 5-hydroxytryptamine and benzylamine, with Ki values of 75 microM for inhibition of MAO-A and 110 microM for inhibition of MAO-B. PMID- 1922691 TI - Morphological changes of striatal dopaminergic presynaptic boutons following intrastriatal kainate injection. AB - Bouton-sparing properties of kainic acid were re-investigated at the fine structural level. Two to 42 days after kainic acid (2.2-5.0 nmol) injection into the rat striatum, nigrostriatal dopaminergic boutons were examined at the injection site using tyrosine hydroxylase immunohistochemistry. Injection of the toxin produced marked dilatations of intensely tyrosine hydroxylase-positive boutons with tremendous amounts of vacuoles. Active astroglial processes reacted with those enlarged, immunoreactive boutons. Thus these boutons, if not all, are interpreted as being in the process of degeneration. Such enlarged boutons were observed more frequently at longer survival times than at shorter ones, suggesting an indirect effect of kainic acid resulting from severe loss of postsynaptic neuronal elements. Morphological changes described here may explain biochemical features that tyrosine hydroxylase level of the kainic acid affected striatum, following initial elevation, gradually decreases at a later stage. PMID- 1922692 TI - Selective effects of behaviorally active doses of methamphetamine on mRNA expression in the gerbil brain. AB - Administration of methamphetamine results in neuronal damage that may be mediated through the production of oxygen-free radicals and modulations in levels of calcium and glutamate in the brain. These changes have been associated with alterations in gene expression, which may play a role in cell damage. To assess the differences in gene expression related to treatment with methamphetamine, levels of mRNA were evaluated for the proto-oncogene c-fos, heat-shock protein (HSP 70) and actin. It was found that c-fos mRNA expression increased in a dose dependent manner after administration of methamphetamine. Whereas, levels of HSP mRNA dropped at small doses of methamphetamine and increased dramatically at large doses. In addition, both c-fos and HSP mRNA showed increased levels throughout the brain. Actin mRNA expression was unaffected by any dose of the drug. At the doses that altered gene expression, methamphetamine produced dose related behavioral changes. Spontaneous locomotor activity was increased at 1.0 mg/kg of methamphetamine, while, larger doses did not alter activity. The data demonstrated that effects of methamphetamine on gene expression occurred within the behaviorally-active dose range and might correlate with the degree of neuronal damage. Selective modulation of gene expression may have a role in determining the acute quantitative and qualitative effects of methamphetamine and the long-term changes that occur after administration of methamphetamine. PMID- 1922693 TI - Involvement of histamine in naloxone-resistant and naloxone-sensitive models of swim stress-induced antinociception in the mouse. AB - The antinociceptive activity of histamine in male mice has been demonstrated using chemical and thermal noxious stimuli and its involvement in naloxone sensitive and naloxone-insensitive models of stress-induced antinociception investigated. In the abdominal constriction test, histamine and dimaprit but not histidine, induced antinociception. Compound 48/80 and H1 antagonists (diphenhydramine, mepyramine and promethazine) and large doses of H2 antagonists (cimetidine and zolantidine) produced antinociception in this test. Antinociception induced by histamine was refractory to mepyramine, metiamide and naloxone. Histamine and non-antinociceptive doses of its antagonists had no influence on the naloxone-resistant warm water swim stress-induced antinociception. In the hot-plate test, histamine agonists, except the H3 agonist (R) alpha-methyl histamine (alpha-MeHA), were antinociceptive but all these agents augmented the naloxone-sensitive room temperature swim stress-induced antinociception, after either intraperitoneal or intraventricular injection. The antinociceptive action of dimaprit was not antagonized by zolantidine which, like other histamine antagonists excluding metiamide, also produced antinociception and enhanced room temperature swim stress-induced antinociception. These findings suggest that histamine is involved in pathways mediating antinociception in the mouse and that such pathways are activated in a naloxone-sensitive model of stress-induced antinociception but not in a naloxone-insensitive model. PMID- 1922694 TI - Effects of acute and chronic systemic administration of some typical antipsychotic drugs on turnover of dopamine and potassium ion-induced release of dopamine in the striatum of the rat in vivo. AB - Chronoamperometry was used to measure the dose dependency of antipsychotic drug (spiperone, haloperidol and chlorpromazine)-induced increases in depolarization stimulated release of dopamine in the striatum of the rat in vivo. The dose response curves were found to be at least biphasic (small doses increased release and large doses inhibited release) and different in shape from dose-response curves for increases in the turnover of dopamine, suggesting that the two processes may not be related. The threshold dose to induce increased depolarization-stimulated release of dopamine correlated with the values in the literature for doses required to block stereotype induced by apomorphine and amphetamine and doses sufficient to cause a maximal increase in release correlated with the doses required for the induction of catalepsy. In addition, the ratio of the doses required to obtain half-maximal and maximal increases in stimulated release of dopamine, matched values in the literature of the ratio of doses required to ameliorate psychotic symptoms, whereas the doses required to reverse the increase induced by antipsychotic drugs did not. Chronic administration of haloperidol resulted in alterations in the dose-response curves for both the release and turnover of DA. Chronic administration caused a reversal of the effect of acute administration in the small dose range (inhibition as opposed to enhancement of release), a decrease in the maximum magnitude of release of dopamine obtained and an overall shift to the right of the dose response curve. Chronic administration of haloperidol decreased turnover, relative to animals receiving the drug acutely and no shift in the position of the dose-response curve was observed. PMID- 1922695 TI - Effect of short- and long-term administration of lithium on the release of endogenous 5-HT in the hippocampus of the rat in vivo and in vitro. AB - The present study determined the effect of short- (3 days) and long- (21 days) term treatment with lithium on the release of 5-hydroxytryptamine (5-HT) form the hippocampus of the rat, measured both in vivo using microdialysis and in vitro using incubated slices. In the in vivo experiments (on the chloral hydrate anaesthetized rat) electrical stimulation of the dorsal raphe nucleus for 20 min evoked an increase of 5-HT in dialysates of hippocampus, which both lasted for the duration of the stimulus and was frequency-dependent (2-10 Hz). Electrical stimulation of the dorsal raphe nucleus, at low stimulation pulse frequencies (2 and 3 Hz), released 3-4 fold more 5-HT in rats treated for 3 days with lithium chloride (3 mmol/kg s.c. twice daily), compared to controls. However, the effect of stimulation of the dorsal raphe nucleus was not altered in rats receiving lithium in the diet for 21 days. Basal levels of 5-HT in hippocampal dialysates for rats receiving long- but not short-term treatment with lithium, were significantly lower than controls. In agreement with the in vivo experiments, the in vitro experiments showed that depolarization (high potassium)-evoked release of endogenous 5-HT from slices of hippocampus of rats treated with short- but not long-term administration of lithium was enhanced compared to controls. These experiments provide direct biochemical evidence that short-term treatment with lithium increases depolarization-evoked release of endogenous 5-HT in the hippocampus, an effect which may be related to the rapid antidepressant actions of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922696 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1922697 TI - Differential secretion of enkephalin-like peptides from bovine adrenal chromaffin cells. AB - Stimulation of chromaffin cells in culture with 1,1-dimethyl-4-phenylpiperazinium (DMPP) or depolarizing concentrations of K+ resulted in a significant secretion of high and low molecular weight enkephalin-like peptides (ELPs) into the culture medium. BioGel P-10 column chromatography was used to characterize the ELPs in chromaffin cell extracts and in culture media before and after stimulation with either DMPP or K+. DMPP (50 microM) stimulation produced a significant secretion of primarily low molecular weight (less than 3 kDa) ELPs whereas 56 mM K+ caused a secretion of both high and low molecular weights ELPs. The expected decrease in cellular content of low molecular weight peptides was not observed regardless of stimulation type. Our results support the hypothesis that the precursor/product ratio of secreted ELPs is dependent upon the nature of the chromaffin cell stimulus. Moreover the cellular content of low molecular weight ELPs is not depleted with either type of stimulation. PMID- 1922698 TI - Structure-activity relationships of mammalian bombesin-like neuropeptides in the contraction of rat uterus. AB - Various peptide derivatives of the C-terminal decapeptide of gastrin releasing peptide (GRP-10) and neuromedin B (NMB), i.e., carboxyl terminal fragments, amino terminal fragments and substituted analogues, were chemically synthesized and the structure-activity relationships of the peptides were investigated by comparing their contractile activities on the rat uterus. Peptides with chain lengths of 8 and 9 amino acid residues from the C-terminus of GRP-10 and NMB, respectively, had considerable contractile activities. At position 6 of both decapeptides, Val seems to be more favourable than Thr for inducing contraction of the rat uterus. The substitution of His at position 3 and Leu at position 9 of GRP-10 by Leu and Phe, as in NMB leads to a decrease in activity. Moreover, Trp at position 4 and Met-NH2 at the C-terminus are essential for activity. Furthermore, in order to characterize the bombesin-receptor profile of rat uterus, the inhibitory effect of two peptide antagonists, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P and [Leu13-phi (CH2NH)-Leu14]-bombesin on the contraction of rat uterus were examined. PMID- 1922699 TI - Progression of experimental infantile hydrocephalus and effects of ventriculoperitoneal shunts: an analysis correlating magnetic resonance imaging with gross morphology. AB - Although previous ultrasonographic studies did monitor ventricular enlargement successfully in experimentally-induced models of feline hydrocephalus, the resolution of neuroanatomic detail was relatively poor after placement of a ventriculoperitoneal (VP) shunt because the skull had ossified over the coronal sutures. Therefore, the present study employed magnetic resonance imaging to follow the progression of ventriculomegaly more accurately, as well as to evaluate the compensatory effects of VP shunting. Hydrocephalus was induced in kittens between 7 and 10 days old by injection of kaolin into the cisterna magna. Age-matched controls received similar injections of saline. At 9 to 14 days after the kaolin injection, the hydrocephalic animals received VP shunts. Anesthetized kittens were scanned at various intervals before and after shunt placement and were killed for morphological correlation. The features observed on the magnetic resonance imaging scans were consistent with the gross morphological changes that accompanied ventricular enlargement. The lateral ventricle began to enlarge as early as 1 day after the kaolin injection, and within 3 days, both the occipital and temporal horns, along with the 4th ventricle, showed signs of moderate dilatation. By 5 days, a bilateral communication had been established through the septum pellucidum. Continued expansion of the ventricular system occurred from 6 to 20 days after injection, to the point where the cerebral cortex was reduced to less than 25% of its original thickness. The internal capsule was stretched and edematous, the caudate nucleus was compressed ventrolaterally, and the cerebellar hemispheres were eroded and/or compressed. Animals in which shunts were successfully placed demonstrated a dramatic improvement in behavior, and a reduction of about 50% in the size of the lateral ventricles within 2 days. In some cases, the lateral ventricles became slit-like within 1 week. When they were killed, about half of the animals that received shunts exhibited mild to moderate ventriculomegaly. These results indicate that magnetic resonance imaging is an excellent method for visualizing the morphological changes associated with this animal model, that these alterations occur soon after the onset of hydrocephalus, and that VP shunting can successfully reduce ventriculomegaly. PMID- 1922700 TI - Intracranial venous hypertension and the effects of venous outflow obstruction in a rat model of arteriovenous fistula. AB - A model of rat arteriovenous fistula (AVF) was created using a proximal common carotid artery to distal external jugular vein anastomosis. Anatomical dissections revealed that the external jugular vein is the primary vessel draining intracranial venous blood. Physiological measurements were made with the AVF open and closed, and during venous outflow occlusion of the contralateral external jugular vein. Opening the AVF increased torcular pressure from 6.5 +/- 0.6 to 13.5 +/- 1.1 mm Hg and decreased mean arterial pressure from 82.7 +/- 1.8 to 62.8 +/- 1.8 mm Hg (both P less than .05), decreasing cerebral perfusion pressure from 76.2 +/- 1.7 to 49.3 +/- 2.2 mm Hg (P less than .05). Middle cerebral artery blood flow velocity (MCA BFV) decreased from 6.8 +/- 1.1 to 4.2 +/- 0.7 cm/s (P less than 0.05). In rats with an AVF, occlusion of venous outflow increased torcular pressure to 34.8 +/- 3.1 mm Hg (P less than 0.05), MCA BFV decreased to 1.8 +/- 0.5 cm/s (P less than 0.05), and severe ischemic changes were seen on the electroencephalogram. Under this condition, torcular pressure and systemic arterial pressure had a positive linear relationship (P less than 0.05), whereas in control rats torcular pressure and arterial pressure had no relationship. Restoration of cerebral perfusion pressure by release of venous outflow occlusion and AVF closure transiently increased MCA BFV to 69% above baseline (P less than 0.05). Histological examination 1 week after permanent venous outflow occlusion revealed venous infarction, subarachnoid hemorrhage, and severe brain edema in rats with an AVF but not in control rats without an AVF. This model of cerebrovascular steal with venous hypertension reproduces both hemodynamic and hemorrhagic complications of human AVF and emphasizes the importance of venous outflow obstruction and venous hypertension in the pathophysiology of these lesions. PMID- 1922701 TI - Neuropsychological sequelae of arteriovenous malformations. AB - A total of 24 patients harboring arteriovenous malformations (AVMs) in either the dominant hemisphere (n = 12) or the nondominant hemisphere (n = 12) were examined neuropsychologically. When compared with 24 matched normal control subjects, the AVM patients demonstrated differential degrees of impairment in verbal or visuospatial processing, depending on whether the lesion involved the dominant or nondominant hemisphere. As predicted, most compelling were the findings of cognitive deficit associated with the hemisphere contralateral to the AVM relative to matched normal control subjects. Evidence of higher cortical dysfunction contralateral to the residing AVM is discussed in the context of cerebrovascular steal. PMID- 1922702 TI - Treatment of cerebral arteriovenous malformations with a combination of preoperative embolization and surgery. AB - Forty-nine patients with cerebral arteriovenous malformations (AVMs) were treated with preoperative embolization followed by resection using a microsurgical approach. In 27 patients, the AVM was located in an eloquent area; in 32 patients, the volume of the AVM was over 20 cm3. Preoperatively, flow-directed embolization was performed in 10 patients (28 procedures), selective embolization with threads was performed in 35 patients (46 procedures), and a combination of flow-directed and selective embolization was performed in 4 patients (12 procedures). The percentage of reduction of the AVM volume averaged 36% after embolization. Five minor complications (transient neurological deficits, in 2 cases associated with ischemic areas on the CT scan) were observed after embolization. The interval between the last embolization and surgery was as follows: within 10 days in 7 patients; between 11 and 20 days in 3 patients; between 21 and 30 days in 10 patients; between 31 and 60 days in 11 patients; and 2 months later in 18 patients. The efficacy of this combined treatment (embolization plus surgery) was evaluated by the incidence of hyperemic complications and the clinical outcome. Hyperemic complications occurred more frequently in patients with an AVM volume greater than 20 cm3. When compared with flow-directed embolization, selective embolization was linked with decreased bleeding during surgery; postoperatively, the incidence of cerebral edema was also lower. Clinical outcome was better after selective embolization, with no occurrence of major deficits and no mortality. When the percentage of reduction of the AVM volume after embolization was 40% or more, the incidence of intraoperative hyperemic complications was lower; moreover, new permanent deficits were never observed in patients with this volume reduction. A retrospective clinical comparison of two groups of patients with similar AVM volumes (greater than 20 cm3)--those given combined treatment (n = 32) versus those treated by direct surgery alone (n = 27)--showed that intraoperative bleeding appeared to decrease in patients treated by embolization; the incidence of postoperative hyperemic complications was not different in the two groups. New major deficits and deaths were less frequent in patients treated by embolization (P = 0.05 for the incidence of major deficits); postoperative epilepsy was also less common in these patients. In conclusion, combined treatment with selective preoperative embolization and direct surgery may help the neurosurgeon in the treatment of large, high-flow AVMs, reducing the risks connected with their surgical removal. PMID- 1922703 TI - Transient hypothermia reduces focal ischemic brain injury in the rat. AB - The effect of transient hypothermia on focal cerebral ischemia was evaluated using a rat model of permanent middle cerebral artery (MCA) occlusion. MCA occlusion was performed on 10 rats at a temporalis muscle temperature of 24 degrees C (hypothermic group) and on 10 rats at 36 degrees C (normothermic group). Rats in the hypothermic group were maintained at 24 degrees C for 1 hour after MCA occlusion and then allowed to rewarm to 36 degrees C over the next 2 hours. Animals in both groups were killed 24 hours after MCA occlusion. Cerebral infarcts were visualized by staining of coronal brain sections with 2,3,5 triphenyltetrazolium chloride. Normothermic rats displayed an average infarct volume of 233.1 +/- 13.2 mm3 (standard error of the mean), whereas hypothermic rats had an average infarct volume of 166.2 +/- 22.8 mm3 (P less than 0.01). Expressed as a percentage of the volume of the right hemisphere, the normothermic group had an infarct volume of 22.1 +/- 1.5% and the hypothermic group an infarct volume of 16.0 +/- 2.2% (P less than 0.05). These results demonstrate that transient hypothermia to a temporalis muscle temperature of 24 degrees C significantly reduces subsequent infarct size in an experimental model of permanent arterial occlusion. PMID- 1922704 TI - Disc herniation in cervical fracture subluxation. AB - Previous reports of computed tomographic scan with contrast myelography in cervical spinal cord injury have shown a rate of disc herniation of less than 5%. We hypothesized that injuries associated with forces adequate to cause bone or ligamentous injury in the region of the disc space could be associated with higher and more significant rates of disc herniation. Thirty-seven consecutive traumatic midcervical fracture subluxations were reviewed. Fracture subluxation was defined by fracture of the facet joints, pedicles, or vertebral bodies or more than 3.5 mm subluxation from C2-C3 to C7-T1. Reduction was achieved in 97% and was not associated with neurological deterioration. On the basis of plain films, tomograms, and plain computed tomographic scans, the injuries were classified as flexion dislocation, flexion compression, compression burst, or extension injuries. Twenty-five computed tomographic scans with contrast myelograms and one magnetic resonance imaging scan were obtained. All patients with partial neurological deficits were studied. A herniated disc was defined as that which deformed the thecal sac and/or nerve roots. Retrospectively, a neuroradiologist reviewed the studies for the presence of herniated disc. Disc herniation was seen at the level of injury in 9 (35%) patients and not seen in other patients. Forty-seven percent of the patients with partial deficits had herniated discs. Herniated disc was seen most frequently in flexion dislocation and flexion compression injuries. Three patients (20%) with partial deficits underwent discectomy. Patients with partial spinal cord injury and discectomy, on average, improved more than other patients with partial spinal cord injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922705 TI - Missile injuries to the brain treated by simple wound closure: results of a protocol during the Lebanese conflict. AB - This is a prospective study of the treatment of penetrating missile injuries to the brain without intracranial surgery carried out at the American University of Beirut Medical Center between 1981 and 1988. Of 600 patients treated for missile injuries to the head, 32 satisfied the study criteria. There were 27 shrapnel and 5 bullet injuries. The mean patient age was 23 years (range, 3-51 years). Twenty patients had intracranial indriven bone fragments. Six patients had exposed brain tissue. The mean follow-up was 3.5 years (range, 1-7.5 years). The superficial entry wound was debrided and closed without drainage in the Emergency Room within a mean of 3 hours (range, 0.5-6 hours), and the patient received methicillin for 14 days. All patients survived and had no or improved neurological deficits. No leakage of the cerebrospinal fluid, infection, or seizures occurred in 31 patients. One patient with indriven bone fragments had leakage of the cerebrospinal fluid and developed seizures and a brain abscess 20 days after the injury. The management of penetrating missile injuries to the brain without intracranial surgery in a select patient population is a reasonable option. This treatment becomes important for a surgeon facing large numbers of casualties, or when operative personnel or resources are limited or unavailable. PMID- 1922706 TI - A three-dimensional micro-organ culture system optimized for in vitro growth of human malignant brain tumors. AB - A brain tumor is composed not only of tumor cells, but also of normal glial, mesenchymal, endothelial, and microglial cells, as well as lymphocytes and macrophages. Therefore, homogeneous cultures of tumor cells, currently used for chemosensitivity testing, do not accurately model in situ tumors. We have developed an in vitro growth assay for brain tumors that includes normal host cells and is potentially useful for studies of chemotherapy and biological response modifiers. Human glioblastoma xenografts (U251-MG) were resected from mice, minced, and explanted into agarose-coated culture wells. After 5 to 7 days, microtumors emerged as expanding spheroids, which grew most efficiently in minimum essential medium supplemented with 20% fetal calf serum, 90% of which was replaced on alternate days. The growth rate and bromodeoxyuridine labeling index were similar in the microtumors and the xenografts, and light microscopy revealed highly cellular, pleomorphic tumors with high mitotic activity in both. Immunohistochemical studies also demonstrated the persistence of macrophages in both xenografts and microtumors. Microtumors treated for 2 hours with 75 mumol/L 1,3-bis-(2-chloroethyl)-1-nitrosourea showed a growth delay of 1.5 days; no effects were observed after treatment with lower doses. This in vitro system for brain tumor culture may provide a useful technique for the study of new therapies as an alternative to in vivo xenograft studies using immunodeficient animals. PMID- 1922707 TI - Surgical access to the base of skull and upper cervical spine by extended maxillotomy. AB - An extended maxillotomy has been developed to permit wider surgical access to the base of the skull. It has proven particularly useful in the management of the previously untreatable neuraxial compression caused by basilar invagination in cases of osteogenesis imperfecta. In addition, patients with extensive extradural space-occupying lesions have been treated. The surgical technique is described and the results of its use in nine patients are presented. PMID- 1922708 TI - Adaptation of rigid fixation to cranial flap replacement. AB - The use of titanium craniofacial plates and the principles of rigid fixation have been adapted to cranial flap replacement. The technique has been in use for more than 18 months with no complications related to the technique or implant. The advantages of using titanium screws and plates to achieve superior healing and cosmesis, as well as the reduction of postoperative artifacts on magnetic resonance imaging and computed tomographic scans, are of benefit to neurosurgical patients. PMID- 1922709 TI - A variable-angled suction nerve root retractor for lumbar spine surgery. AB - A simple, variable-angled suction nerve root retractor is described for use primarily in lumbar disc surgery. PMID- 1922710 TI - Surgical treatment of intractable epilepsy associated with schizencephaly. AB - With the advent of magnetic resonance imaging, there has been an increased recognition of schizencephaly during life, especially in epileptic patients. We report our experience with the assessment and treatment of three patients with medically intractable seizures associated with this condition. The three men were aged 24 to 37 years. Two had delayed developmental milestones and hemiparesis or hemiplegia. One had normal development and a normal neurological examination. Seizures began between the ages of 15 and 19 years and lasted for 5 to 22 years before surgery. All had partial simple or generalized seizures with predominant electroencephalographic and electrocorticographic epileptic activity localized to temporal and frontal lobes on the side of the lesion. Neuropsychological assessment indicated widespread dysfunction maximal at the areas of predominant electroencephalographic abnormality. Magnetic resonance imaging demonstrated anterior parasagittal, parietal, and Rolandic cerebral clefts, with ventricular diverticuli, gray matter heterotopia, polymicrogyria, and a true agenesis of the corpus callosum in individual patients. The patients underwent temporal (one patient) and frontotemporal (two patients) lobectomies without additional neurological deficits or neuropsychological deterioration. Postoperative follow up showed reduction in seizure frequency. We conclude that the surgical treatment of epilepsy is well tolerated in such patients, and their seizures can be alleviated by resection of epileptogenic areas. PMID- 1922711 TI - Percutaneous drainage and serial magnetic resonance imaging in the diagnosis of symptomatic posttraumatic syringomyelia: case report and review of the literature. AB - A patient with high cervical tetraplegia with new-onset headaches and posttraumatic syringomyelia is presented. Percutaneous drainage of the syrinx resulted in a resolution of the headaches and collapse of the syrinx on follow-up magnetic resonance imaging (MRI). The return of the symptoms correlated with the re-expansion of the syrinx on MRI. The patient underwent syringopleural shunting with persistent resolution of the symptoms and collapse of the syrinx on MRI. The value of percutaneous drainage and serial MRI to determine the clinical significance of posttraumatic syringomyelia is discussed. PMID- 1922712 TI - Screening for unruptured familial intracranial aneurysms: subarachnoid hemorrhage 2 years after angiography negative for aneurysms. AB - The screening of asymptomatic individuals in families with intracranial aneurysms has been advocated to detect unruptured aneurysms before a major hemorrhage occurs. We report a 39-year-old male member of a large Dutch family, with a documented history of intracranial aneurysms, who suffered a subarachnoid hemorrhage 2 years after cerebral digital subtraction angiography using intravenously administered contrast medium showed no abnormalities. Conventional arteriography demonstrated three intracranial aneurysms measuring 3 x 3 mm. Potential alternative screening procedures are discussed. PMID- 1922713 TI - Traumatic aneurysm of the posterior inferior cerebellar artery: case report. AB - We report a case of a traumatic aneurysm of the posterior inferior cerebellar artery caused by an occipital fracture. The necessity to suspect a vascular traumatic lesion when an unusual subarachnoid hemorrhage is seen on the computed tomographic scan in a case of trauma is stressed. PMID- 1922714 TI - Chordoma in early childhood: a clinicopathological study. AB - A case of clival chordoma in a 4-year-old girl is presented. The tumor regrew rapidly after it was partially removed, and the patient died after a clinical course of 11 months. An autopsy revealed a massive clival mass and widespread metastases in the dura mater, skull bone, bilateral lungs, liver, sternum, left humerus, and vertebrae. Pathological findings showed that the tumor cells were poorly differentiated, with a rare, but typical, physaliphorous appearance. The presence of epithelial differentiation proteins, mitochondria surrounded by rough endoplasmic reticulum, and desmosomes was demonstrated in the tumor cells both immunohistochemically and ultrastructurally. Thus, the tumor was diagnosed as a chordoma. The literature pertaining to intracranial chordoma in early childhood is reviewed. Rapid growth and distant metastases may occur in chordomas at a young age. PMID- 1922715 TI - Craniopharyngioma of the posterior fossa. AB - A case of craniopharyngioma originating in the very unusual location of the posterior fossa is presented. The patient, a 23-year-old man, was operated on at another hospital when he was 3 years old for craniopharyngioma in the suprasellar area. There was no complaint for several years after this initial operation. Three months before he was admitted to our hospital, he had complaints of headache, vomiting, nausea, and ataxia. A computed tomographic scan revealed a mass with a cyst and calcifications in the posterior fossa. The tumor was removed totally. PMID- 1922716 TI - Malignant carcinoid tumor metastatic to the dura mater simulating a meningioma. AB - A 50-year-old man, transferred from another hospital, was admitted because of adult onset seizures. Nine months earlier, he had undergone an esophagogastrectomy; the lesion was confirmed to be a carcinoid tumor. Laboratory tests, chest x-rays, and electrocardiogram were normal. A second liver and spleen scan was performed. A computed tomographic scan revealed a well-circumscribed homogeneous enhancement of a lesion in the left frontal superficial area. On the 10th day, the patient underwent a left frontal parietal craniotomy. Postoperatively, he manifested no residual neurological deficits and was discharged on the 6th postoperative day. A week later, he was readmitted for treatment of aphasia and right hemiparesis; he was treated and discharged. The patient survived 16 more months. The occurrence of central nervous system metastasis from carcinoid tumor is rare. This tumor resembled, in many respects, a parasagittal meningioma. Radiological findings on the computed tomographic scan were typical of these tumors. This patient was diagnosed as having metastatic disease just 9 months after the diagnosis of the primary tumor and 13 months from the onset of any symptoms. This is a short period of time compared with that reported in other cases. PMID- 1922717 TI - Multiple growths of primary calvarial meningiomas. AB - The authors present the case of a 68-year-old woman with multiple growths of primary calvarial meningiomas. Histological examination revealed one tumor arising in the left parietal bone that showed some malignant aspects, including hypercellularity, cellular pleomorphism, necrotic foci, and some mitoses; the tumor partially had a meningotheliomatous pattern. Two other tumors in the right parietal bone were meningotheliomatous meningiomas without any malignant features. With a review of the literature, the pathogenesis of the multiplicity is discussed. PMID- 1922718 TI - Accessory nerve neurinoma manifesting with typical jugular foramen syndrome. AB - A case of neurinoma arising from the accessory nerve is reported. The tumor was small and located entirely within the jugular foramen; the patient sought treatment for a jugular foramen syndrome. The lesion was visualized only on magnetic resonance imaging, and surgery confirmed that it originated from a cranial root of the accessory nerve. There have been no previous reports of a small, accessory neurinoma that is confined entirely to the jugular foramen, appearing with a typical jugular foramen syndrome. PMID- 1922719 TI - Posterior fossa epithelial cyst of ectodermal origin. AB - The case of a large ventral cyst of the posterior fossa of probable ectodermal origin in a 33-year-old patient is presented. Intracranial epithelial cysts are rare, and their histogenesis is a subject of controversy. Previous reports have hypothesized either a neuroepithelial or endodermal origin for the majority of these cysts. This case is unusual because it is the first case, to our knowledge, where melanocytes and melanin have been demonstrated within the cyst wall. These findings suggest an ectodermal origin for this cyst. PMID- 1922720 TI - Acute aggravation of subdural effusion associated with pachymeningitis carcinomatosa: case report. AB - The authors present a case of acute aggravation of subdural effusion associated with pachymeningitis carcinomatosa. Microscopic examination of a surgical specimen revealed diffuse involvement of the dura mater by a metastatic adenocarcinoma in which the tumor cells invaded venules located in the areolar layer in particular. The rapid increase in capillary transmural pressure resulted in extravasation of plasma components, causing an increase in subdural effusion. PMID- 1922721 TI - Spinal invasion of pulmonary hydatidosis: computed tomographic demonstration. AB - A case of pulmonary hydatidosis in which cysts caused spinal cord compression is presented. To our knowledge, spinal invasion after pulmonary hydatidosis has not been demonstrated previously. PMID- 1922722 TI - Intradural cervical lipoma in a neurologically intact patient: case report. AB - The authors report an unusual intradural subpial lipoma of the cervical spinal cord in a neurologically intact adolescent. The patient sought treatment for neck pain and had a history of previous trauma. Magnetic resonance imaging revealed the lesion. There are no reported cases of a subpial lipoma detected in the absence of any neurological deficits. A subtotal excision was performed, and pathological studies confirmed the diagnosis. Postoperatively, the patient remained neurologically intact. PMID- 1922723 TI - Infection of a shunt by Mycobacterium fortuitum: case report. AB - Mycobacterium fortuitum is a rare cause of central nervous system infection; however, shunt infection caused by this organism has not been reported. We report a case of shunt infection subsequent to insertion of a ventriculoatrial shunt for obstructive hydrocephalus caused by a cerebellar hematoma. The shunt infection was controlled by removal of the shunt and a combination of systemic and intraventricular administration of amikacin, and oral administration of ofloxacin. The case is discussed and the pertinent literature reviewed. PMID- 1922724 TI - Spontaneous decerebrate movement after declaration of brain death. PMID- 1922725 TI - Histological diagnosis of intracranial tuberculomas. PMID- 1922726 TI - Effect of etomidate on motor evoked potentials in monkeys. PMID- 1922727 TI - Ultrastructure of the serotoninergic system of the motor region of the cerebral cortex. PMID- 1922728 TI - Cellular organization of the paraventricular nuclei of the rat hypothalamus. PMID- 1922729 TI - Kinematic analysis of the formation of precise instrumental movements in cats. AB - The kinematic parameters of the manipulatory motor reactions in the dynamics of the formation and consolidation of a precision skill consisting in the displacement and subsequent holding of a lever in a zone of "work" space signalized by a sound were studied in experiments on cats. It was established that the development of the skill passes through a stage of disinhibition of slow movements with a prolonged increase, prior to the appearance of the sound signal, in velocity. The skill which is consolidated in the course of subsequent training sessions is accomplished by uniform movements of the ballistic type, and is characterized by independance from the acoustic indication of the final position. At the same time, the relationship of the duration of the increase in acceleration to the beginning of the inhibition of the movement becomes an invariant parameter of the central program of the precision reactions. PMID- 1922730 TI - Stability of the behavioral specialization of neurons. AB - The constancy of the association of the activity of the neurons of the limbic cortex and food-procuring behavior has been analyzed in neurons specially selected on the basis of the criterion of length of recording in experiments in rabbits. Comparison of the activity in the first and second halves of the period was carried on the basis of the average frequency for the time of each half of the recording, the average frequency in each of 10 distinctive acts of cyclical behavior, as well as on the basis of the probability of the presence of activation in these acts. It was demonstrated that behavioral specialization, defined as the presence of 100% activation of the cell in specific acts, did not change in the course of the recording, and was a stable information-containing characteristic of the association of the activity of the neuron with the animal's behavior. PMID- 1922731 TI - Reflection of the operations of comparison of current afferentation with internal pretuning in the impulse activity of neurons of the frontal cortex of the dog. AB - When the differentiation of the classical (salivary) conditioned reflex (CR) is carried out by dogs, two groups of neurons are distinguished in their frontal cortex, for which a specific type of relationships between the current conditional and unconditional (CS and US) signals and the character of the internal pretuning to the perception of the given stimuli is the condition. The reactions of the neurons of the first group developed in response to the US only when the tracking schedule of the US was characterized by regularity. These reactions disappeared when there was any sudden deviation from the standard schedule of the of the CS-US combination for the animal, or when there was a change in the parameters of these signals, and they recovered as the repeated presentations of the CS or the US with the changed parameters proceeded. The reactions of the neurons of the second group developed in response to the presentation of the CS only when this stimulus followed a stimulus which was opposite to it in significance. The reactions of the neurons of the first group are associated with the processes of the detection of the correspondence of the sensory pretuning to the actual stimulus, while the reactions of the neurons of the second group are regarded as the result of the disparity between the characteristics of the current afferentation and the "internal model" of the stimulus. PMID- 1922732 TI - Comparative psychological approach to the analysis of the functions of the hippocampus. AB - As compared with dogs, the development of conditioned reflex switching-over of heterogeneous conditioned reflexes in intact rats is often accompanied by the development of reactions of the neurotic type. Experiments involving injury of the hippocampus (in rats) and the recording of electrical activity (in dogs) showed that this structure participates in the formation of conditioned reflex switching-over of instrumental reflexes. Following the injury to the hippocampus, the rats successfully formed the switch-over. The switch-over signal altered the electrical activity of the hippocampus in the dogs. Consequently, the hippocampus in both species of animals belongs to the system of structures which participate in the formation of conditioned reflex switching-over. Hippocampectomized rats were not capable of developing an alimentary conditioned reflex at the 30% level of reinforcement. The highest values of the frequency of the hippocampal theta rhythm were obtained in the dogs at just this level of probability of reinforcement. These data indicate that the assurance of reactions to signals with a low probability of reinforcement is an important function of the hippocampus in various species of animals. PMID- 1922733 TI - Reflection of the level of alimentary motivation in the electrical activity of the esophageal muscles of the rabbit in the process of reinforcement. PMID- 1922734 TI - Habituation of completely isolated neurons of the edible snail to electrical stimulation. PMID- 1922735 TI - Influence of hydrocortisone on the activity of 5'-nucleotidase and adenosine deaminase in the hypothalamus and hippocampus of the rat brain. PMID- 1922736 TI - Metabolism of testosterone in discrete regions of the brain of rat embryos. PMID- 1922737 TI - Central neurophysiologic mechanisms of the regulation of inhibition. AB - The neuronal populations of the cuneate nucleus of the midbrain, the medial parabrachial nucleus, the median and magnus nuclei of the raphe, the electrical and local chemical stimulation of which elicits the inhibition of the motor activity of animals, were determined in chronic experiments on freely-moving white male mongrel rats. It was established that when each of the enumerated regions of the brain are stimulated electrically in other zones which elicit motor inhibition, multineuronal responses with a latent period of less than 2.5 msec were recorded. At the same time, multidirectional bilateral changes in muscle tone of the flexors and extensors of the hind limbs are observed in sodium ethaminal anesthetized and unanesthetized animals. The electrolytic destruction of the inhibitory zones of the median raphe nucleus and raphe nucleus magnus blocks the motor inhibition elicited by electrical stimulation of the cuneate nucleus of the midbrain and the medial parabrachial nucleus. PMID- 1922738 TI - Comparative neurophysiologic analysis of trace processes in delayed spatial choice and the trace conditioned reflex in rhesus macaques. PMID- 1922739 TI - Time course of the redox state potential of the cerebral cortex, developing as a reaction to implanted platinum electrodes. AB - The time course of the redox-state potential of the brain (ROSP) of the brain was investigated in five series of chronic experiments in rabbits with different numbers of electrodes (8-12, 22-25, 50) implanted to the level of the dura mater, with 10-12 electrodes implanted to the level of the pia mater, and with four to eight pairs of electrodes implanted in the cortical layer to a distance of 1.5-2 mm. It was found that the ROSP undergoes a number of fluctuations in the negative and positive directions with a gradually decreasing amplitude in the course of 5 25 days following the operation, after which relatively stable negative values of the ROSP are established on the average in electrodes implanted to the level of the dura mater, and positive values in electrodes implanted to the level of the pia mater. PMID- 1922740 TI - Features of stuttering preschool children. PMID- 1922741 TI - Spontaneous intracerebral hematomas from vascular causes. Predictive value of CT compared with angiography. AB - The aim of the present study was to assess the diagnostic accuracy of CT in determining the underlying causes of brain hematomas with a state-of-the art CT. For this purpose, CT and angiographic data of 149 subjects with spontaneous intracerebral hematomas (ICH) were statistically compared in a blind, retrospective study, taking angiography, supported when possible by surgical findings, as providing the correct diagnoses. 5 groups were distinguished on the basis of CT data: 103 patients with isolated deep ICH had normal angiograms; 9 patients with isolated superficial ICH and 8 with deep ICH and intraventricular hemorrhage (IVH) had arteriovenous malformations (AVMs). 4 with this combination showed no angiographic abnormalities, one had an aneurysm. 14 subjects with ICH and subarachnoid hemorrhage (SAH) had a middle cerebral or carotid artery aneurysm; and 10 with ICH, SAH and IVH had also an aneurysm, in 7 on the anterior communicating artery. Sensitivity, specificity, positive and negative predictive values were respectively: for AVMs 100, 96, 77 and 100%; and for aneurysms 96, 100, 100 and 99%. Kendall coefficient was 0.95, indicating close correlation between the two modalities. This study confirms that CT can accurately predict the likelihood, nature and location of vascular ICHs. It indicates whether angiography is necessary or not, and if so, what vascular tree ought to be explored. PMID- 1922742 TI - Capsular and thalamic infarction caused by tentorial herniation subsequent to head trauma. AB - Five patients (4 male and 1 female) were observed to have capsular and thalamic infarction ascribed to descending transtentorial herniation (DTH) caused by head injury. A lucid interval immediately after the trauma and the presence of an epidural hematoma (EDH) characterized all five cases. At the time of hospitalization consciousness was seriously impaired and signs of cerebral herniation were apparent. Two to four days after the trauma, low attenuation in the computed tomography (CT) images pinpointed intracerebral damage in the anterolateral part of the thalamus and in the internal capsule on the same side as that of the EDH in three patients, and in the other two patients bilateral thalamic and capsular damage was noted. The low attenuation implicated the perforating arteries, that is the anterior thalamoperforating and anterior choroidal arteries, suggesting infarcted regions caused by occlusion of these arteries. Findings in the present study suggest that arterial occlusion in closed head injury may result from DTH. Moreover, infarction may be attributed to the delayed effects of injury. PMID- 1922743 TI - Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia. AB - Cerebral glucose metabolism of 18 patients with multi-infarct dementia (MID) and 10 age-matched normal subjects were examined with positron emission tomography and the 18-F-fluoro-deoxy-glucose technique. MID patients had significantly lower glucose metabolism in all the grey matter regions measured and were also characterized by more individuality in metabolic pattern. MID patients were also evaluated as to intelligence quotient (IQ). A positive correlation between IQ as shown by the Tanaka-Binet test and glucose metabolism for the entire grey matter was found. The clinical applicability of this test for predicting cerebral metabolism is discussed. PMID- 1922744 TI - Increased rCBF in gray matter heterotopias detected by SPECT using 99mTc hexamethyl-propylenamine oxime. AB - Imaging findings of morphology and regional cerebral blood flow in two patients suffering from epileptic seizures are presented. CT and MRI revealed heterotopic gray matter as a probable structural correlate, causing the seizure disorder. 99mTc hexamethyl-propylenamine oxime (HM-PAO) SPECT demonstrated focally increased regional cerebral blood flow in both patients in the areas of their heterotopic lesions. Heterotopic and orthotopic gray matter seem to have similar features in terms of regional perfusion. A focally increased brain perfusion in interictal epileptic patients may indicate an underlying migration anomaly. PMID- 1922745 TI - The effect of iohexol on brainstem auditory evoked potentials. A prospective study on 30 patients. AB - A prospective study was made to evaluate the effect of intrathecal injection of iohexol on brainstem auditory evoked potentials (BAEP) following myeloradiculography, in order to assess its neurotoxicity. Thirty patients who received contrast medium via the lumbar route for myeloradiculography (cervical level = 25 patients, lumbar level = 5 patients) had BAEP examinations before, 2 h and 24 h after myelography. No statistically significant prolongation of absolute and interpeak latencies was found between premyelographic and postmyelographic records. Low incidence (20%) of insignificant clinical adverse effect following myelography was also noted in the same group of patient. PMID- 1922746 TI - Shortcomings and pitfalls of ocular MRI. AB - MRI was performed in 41 patients with ocular lesions: 27 cases of malignant melanoma, 5 of haemorrhage, 3 of choroidal metastasis, 3 of senile disciform macular degeneration, 2 retinoblastomas and 1 hamartoma. On MRI 5 small lesions (less than 2 mm thick): 1 melanoma, the 3 metastases and the hamartoma, were not seen. All the malignant melanomas visualised were hyperintense compared to the vitreous on T1-weighted images. On T2-weighted images 24 of 26 lesions were hypointense compared to the vitreous. The remaining two lesions were almost isointense, corresponding to amelanotic lesions. These MRI features did not differ significantly from those of retinoblastomas, senile disciform macular degeneration or subacute choroidal haemorrhage. Major shortcomings of MRI in lesions of the globe lie in a lack of spatial resolution and poor specificity of the findings. PMID- 1922747 TI - X-linked deafness, stapes gushers and a distinctive defect of the inner ear. AB - The association of X-linked mixed deafness with stapes gusher has been recognized for 20 years, and imaging studies by polytomography have shown dilatation of the lateral end of the internal auditory meatus (IAM) in some cases. We have made genetic linkage studies in 7 pedigrees in whom deafness was inherited in an X linked manner. All patients had a full range of audiometric and vestibular function tests. Thin section high resolution CT in two planes was used to assess the state of the middle and inner ears. We found a distinctive inner ear deformity in some of the deaf males characterised not only by a wide bulbous IAM but more importantly, by deficient or absent bone between the lateral end of the IAM and the basal turn of the cochlea. We believe that this results in a communication between the subarachnoid space in the IAM and the perilymph in the cochlea, leading to perilymphatic hydrops and a "gusher" if the stapes is disturbed. Moreover, some of the obligate female carriers seem to have a milder form of the same anomaly associated with slight hearing loss. Genetic studies on some of the deaf males with apparently normal inner ear anatomy suggest a different locus on the X chromosome and hence a different pathogenesis for the deafness. PMID- 1922748 TI - Thickened fatty filum terminale: MR imaging. AB - MR images of four patients with a thickened filum terminale showing a fat signal are presented. There were no related symptoms and no evidence of tethering. The thickened fatty filum terminale seemed to be a developmental anomaly and without clinical significance. As the incidence of this anomaly was 0.24% in our series, knowledge of its possible presence of this anomaly is important for routine reviews of MR image. PMID- 1922749 TI - The value of pre-operative embolisation of meningioma estimated subjectively and objectively. AB - In a personal series a comparison has been made of the subjective and objective assessments of benefit between a group of patients in whom preoperative embolisation for meningioma was performed and a group, referred during the same timescale, in whom embolisation was either not possible or not appropriate. Preoperative difficulty with bleeding was experienced in 25% of the embolisation group and in 62% of the non-embolised group. Blood replacement overall was less in the embolised patients. Surgical complications occurred in 21% of those embolised but in 54% of those in whom embolisation had not been performed. At follow-up the outcome was rated as good in 79% in the embolisation group as opposed to 58% in the non-embolised group. Preoperative embolisation was therefore beneficial. PMID- 1922750 TI - Hema and latex: a dangerous combination? AB - The endovascular treatment of intracranial aneurysms with detachable balloons requires filling materials that harden reliably and are compatible with the balloon. While the incompatibility of latex balloons and hema from different manufacturers is known, no incompatibility has been assumed thus far if both balloon and hema were from the same manufacturer. In two series of experiments, we filled a total of 20 latex balloons with hema as recommended by the balloon manufacturer. Within an observation time of 4 weeks all latex balloons ruptured. At the time of rupture, the balloons had gained 5-10% in weight, most likely due to osmotic shifts in water. Simultaneously, hardening of the hema resulted in a loss of elasticity of the latex. Until these compatibility problems are solved, silicone rather than latex balloons should be used with permanent filling materials such as hema for the endovascular treatment of intracranial aneurysms. PMID- 1922751 TI - Do arachnoid cysts grow? A retrospective CT volumetric study. AB - The volumes of intracranial arachnoid cysts were measured in 136 CT scans of 86 patients. Absolute and relative cyst size was calculated. Left hemisphere and middle cranial fossa location prevailed. A slight negative correlation of relative cyst size with age (r = -0.21, NS) disappeared when analysis was restricted to the adult age group (greater than or equal to 20 years). After the sample was divided into two groups according to relative cyst size (cysts less than mean volume vs cysts greater than mean volume), small AC showed no correlation with age, while large AC correlated positively with age (r = 0.79, P less than 0.05). A subgroup of large AC appears to expand with time, while the majority of small AC remain unchanged. PMID- 1922752 TI - MRI demonstration of uncal herniation caused by arachnoid cyst in the Sylvian fissure. AB - We report a case of arachnoid cyst in the Sylvian fissure which progressed to uncal herniation. MRI was shown to be superior in visualizing uncal herniation. PMID- 1922753 TI - Extradural epidermoid tumor of the frontal bone. AB - The radiologic findings in a case of an extradural diploic epidermoid tumor (ET) of the frontal bone, examined with plain X rays, CT and MRI, are reported. A head injury with traumatic inclusion of epidermis could have been the origin of the tumor. This report stresses the importance of the plain skull X ray in the diagnosis of extradural ET. PMID- 1922754 TI - "Unusual" MRI appearance of sphenoid sinus mucocele. AB - The authors report a case of sphenoid sinus mucocele which exhibited unusual MRI features. However a review of the literature shows that these lesions may present with different MRI appearances probably related to the variability of the cyst content. Further series are needed for a better definition of the MRI behaviour of the lesions. PMID- 1922755 TI - Meningioma of the third ventricle. Computed tomography and magnetic resonance imaging. AB - Meningiomas of the third ventricle are rare intracranial neoplasms. We reported such a case in a 42 years old man without clinical evidence of increased intracranial pressure. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated the tumour sitting in the superior and anterior part of the third ventricle, bulging into the lateral ventricles. CT was more effective than MRI in the demonstration of calcifications whereas MRI proved to be superior in delineation of the tumour and its relation with surrounding structures. PMID- 1922756 TI - Cerebral ganglioglioma and neurofibromatosis type I. Case report and review of the literature. PMID- 1922757 TI - CT and MR imaging of acute cerebellar ataxia. AB - An adult female showed mild cerebellar ataxia and CSF pleocytosis following an acute infection of the upper respiratory tract, and was diagnosed as having acute cerebellar ataxia (ACA). CT and MR appearances in the acute stage revealed moderate swelling of the cerebellum and bilaterally increased signal intensity in the cerebellar cortex. PMID- 1922758 TI - High signal intensity of both putamina in patients with HIV infection. AB - We report two patients with HIV infection whose MR imaging showed abnormal high signal intensity confined to both putamina on T2-weighted spin echo (SE) images. We assume that they may represent the early manifestations of HIV encephalitis. PMID- 1922759 TI - Serial MR imaging in Creutzfeldt-Jakob disease. AB - Serial magnetic resonance (MR) imagings of two autopsied patients with Creutzfeldt-Jakob disease (CJD) are presented. Both patients showed a dramatic progression of brain atrophy. The initial MR imagings were, however, interpreted as normal except for localized mild cortical atrophy in one patient. When a normal MR image is obtained in a demented middle-aged or aged patient, CJD may still need to be ruled out: follow up MR imaging may be useful. PMID- 1922760 TI - MR findings in leukodystrophy. AB - Up to 5 years ago, the radiological diagnosis of leukodystrophy was based on computed tomography (CT). More recently, magnetic resonance imaging (MRI) has been used to study pathology of the white matter with great success. The abnormalities in eight patients with different types of leukodystrophy are described, using high-field MRI. CT and MRI show comparable sensitivity in detecting the pathological changes of leukodystrophy. MRI seems to be superior in visualizing the extent of the lesions, their precise anatomical location and any involvement of the brain stem and cerebellum. Differential diagnosis among the three types of leukodystrophy by MRI is difficult but may be attempted by some features. Specific diagnosis can be achieved only by laboratory examination or histology. The role of MRI should be to suggest the proper biochemical test at an earlier stage. PMID- 1922761 TI - Magnetic resonance imaging in toxic encephalopathy due to podophyllin poisoning. AB - A case of toxic encephalopathy due to podophyllin poisoning was presented. It is documented for the first time by MRI that diffuse cerebral atrophy occurred as a result of podophyllin toxicity. PMID- 1922762 TI - Vanishing calcification of the brain in an infant after open heart surgery. AB - Neurological complications after cardiac operations with the aid of cardiopulmonary bypass and hypothermia are well known. A 6 months-old child is described with severe neurological complications after cardiac surgery for Fallot's tetralogy. On the CT scan cortical calcification was seen to vanish. Such calcification has not been reported in similar patients. Possible causes are discussed but the precise pathophysiology of this phenomenon remains unclear. PMID- 1922763 TI - Immunocytochemistry of the taurine biosynthesis enzyme, cysteine sulfinate decarboxylase, in the cerebellum: evidence for a glial localization. AB - Immunocytochemistry of cysteine sulfinate decarboxylase was developed in the cerebellum with an antiserum that we have recently produced using as immunogen a homogeneous fraction purified about 2000-fold from liver. In the rat, this antiserum immunoprecipitated the enzymatic activity from brain, labeled one band (molecular weight = 51,000) on immunoblots of an enriched fraction from brain but none with a brain crude extract and thus appeared to be specific. In the cerebellum numerous immunolabeled cells were found in the white matter that were typically arranged in rows like oligodendrocytes. A few immunolabeled cells were scattered in the granular layer. Around the Purkinje cells numerous small satellite cells were immunostained that sent faintly labeled radial fibers through the molecular layer. These cells were thus identified as Golgi epithelial cells with their Bergmann fibers. Purkinje cells were not labeled either at the cell body or at the nerve ending levels. In the molecular layer no cells were found consistently and convincingly immunolabeled that could correspond to the stellate cells. No immunopositive punctae typical of the interneuron nerve endings were ever observed. A significant cysteine sulfinate decarboxylase activity was also measured in glial cell fractions enriched in oligodendrocytes and astrocytes respectively. The glial localization of taurine biosynthesis enzyme in the cerebellum does not support the hypothesis that it could be involved in neurotransmission, but rather suggests that taurine is manufactured by glial cells and accordingly may play a physiological role in relation to glial function. PMID- 1922764 TI - Organization and dynamics of microtubules in Torpedo marmorata electrocyte: selective association with specialized domains of the postsynaptic membrane. AB - The distribution and subcellular organization of two components of the secretory pathway, the Golgi apparatus and microtubules, have been investigated in Torpedo marmorata electrocyte. This highly polarized syncytium, embryologically derived from skeletal muscle cells, displays distinct plasma membrane domains on its innervated and non-innervated faces, and it played a critical role in the identification of the acetylcholine receptor. By immunocytochemical analysis, we show that in the electrocyte, numerous focal Golgi bodies are dispersed throughout the cytoplasm in frequent association with nuclei. Under experimental conditions known to stabilize microtubules, we reveal an elaborate network composed of two populations of microtubules exhibiting different dynamic properties as evaluated by cold-stability, resistance to nocodazole and post translational modification. This network appears organized from several nucleating centers located in the medial plane of the cell that are devoided of centrioles. The network displays an asymmetric distribution with individual microtubules converging towards the troughs of the postsynaptic membrane folds. In these particular regions, we consistently observed clusters of non-coated vesicles in association with the microtubules. The organization of the microtubules in the electrocyte may thus result in a functional polarization of the cytoplasm. In other polarized cells, the particular organization of the secretory pathway accounts for the intracellular routing of membrane proteins. The organization that we have observed in the electrocyte may thus lead to the vectorial delivery of synaptic proteins to the innervated plasma membrane. Furthermore, the abundance of synaptic proteins makes the electrocyte a unique model with which to decipher the mechanisms involved in the sorting and targeting of these glycoproteins. PMID- 1922765 TI - Distribution and density of GABA cells in intralaminar and adjacent nuclei of monkey thalamus. AB - The density of GABA-immunoreactive neurons was examined in the intralaminar and certain principal relay nuclei of the macaque monkey thalamus. Counts were made in 10-microns-thick frozen sections and in 1-micron-thick plastic sections and stereological formulae applied to obtain an accurate assessment of the volumetric density of GABA cells in the nuclei. It was found that GABA-immunoreactive cells account for at least 27% of the cells per unit area of all the thalamic nuclei investigated and up to as much as 50% by unit volume. The intralaminar nuclei show only slightly fewer GABA cells than the principal relay nuclei. Previous reports of their absence or relatively low numbers in the intralaminar nuclei probably stem from their smaller size, relatively weaker immunoreactive staining and from failure to apply stereometric formulae that reveal the density of neurons per volume of tissue. These results suggest that the cellular elements of the intralaminar nuclei are not fundamentally different from those of the principal relay nuclei of the thalamus. PMID- 1922766 TI - In vitro formation of type 2 astrocytes derived from postnatal rat hypothalamus or cerebral cortex. AB - The origin and function of type 2 astrocytes in the optic nerve are now well described, but there are few and controversial observations concerning their origin and functional significance in other regions of the mammalian brain. We here describe primary and highly enriched secondary glial cultures obtained from postnatal (P0-P6) rat hypothalami and cerebral cortices that included glial cells with morphological and immunocytochemical characteristics of type 2 astrocytes. The somata of such astrocytes were characteristically small and polygonal; they bore several processes with few branches. They were highly immunoreactive for glial fibrillary acidic protein and the surface antigens, A2B5 and NSP4; they were immunonegative for myelin basic protein and galactocerebroside. They grew on top of a continuous monolayer of much larger, flattened cells, that were glial fibrillary acidic protein-positive but A2B5- and NSP4-negative. In cultures derived from tissues younger than postnatal day 4, their appearance required the addition of adult (horse) serum to the culture milieu; they appeared spontaneously in cultures from older animals. Analysis of the origin of these cells, including experiments using tritiated thymidine incorporation, indicated that these astrocytes resulted from asymmetric divisions of the flat glial cells in the basal layer of the cultures. After their first appearance which varied according to the age of the source tissue, they were continuously generated, with a generation time no longer than 48 h; the life-span of individual cells was found to not exceed one week in neuron-free primary glial cultures. They displayed important process motility but did not show any significant migratory activity. The ready inducibility of glial cells showing many characteristics of type 2 astrocytes, in cultures derived from different brain areas, suggests that type 2-like astrocytes or their committed precursors are not restricted to particular neural structures, but are probably widely distributed within the mammalian brain. Their functional significance within the different brain areas remains to be determined. PMID- 1922767 TI - Ontogenesis of the hypothalamic catecholaminergic system in rats: synthesis, uptake and release of catecholamines. AB - The development of the hypothalamic catecholaminergic system during ontogenesis in rats has been studied with glyoxylic acid histofluorescent method in vivo and with isotopic biochemical technique in vitro. It has been demonstrated that at the 15th fetal day the catecholaminergic system was functionally inactive at least in its ability for the uptake and K(+)-stimulated release of catecholamines. Since the 16th fetal day, hypothalamic neuronal elements gained an ability for synthesis of catecholamines, their specific uptake and K(+)-evoked release. Over the subsequent two days, the intensity of the fluorescent intraneuronal product rose considerably showing the increase of either synthesis or accumulation of catecholamines. Simultaneously, the values of the uptake and K(+)-stimulated release of the exogenous radioactively-labelled dopamine increased significantly. The intensity of the fluorescence of the hypothalamic neuronal elements dropped from 20th fetal until the ninth postnatal day, whereas the specific uptake doubled over the same period reaching its adult level. By the 21st postnatal day the reaccumulation of the fluorescent product occurred. PMID- 1922768 TI - Effects of central and peripheral inputs on single pineal cell activity in the rat. AB - The influences exerted by central and peripheral afferents to the pineal gland have been studied in rats anesthetized with urethane (1.2 g/kg, i.p.). Spontaneous action potentials arising from the pinealocytes were recorded by means of glass micropipettes filled with 3 M NaCl containing a dye. The electrical stimulation of suprachiasmatic nucleus, superior cervical ganglia, sciatic nerve and retina evoked discharge changes in a significant number of pineal cells. However, a relatively higher proportion of pinealocytes failed to respond to these afferents. Three types of responses could be observed. Inhibitions were the predominant response patterns to suprachiasmatic nucleus, superior cervical ganglia and sciatic nerve, while excitations were mainly elicited following photic stimulation, whereas the remaining evoked activity was biphasic responses, which were observed in a small number of cells after stimulation of suprachiasmatic nucleus, superior cervical ganglia and retina. These data confirm some previous neural inputs to the pineal and demonstrate the existence of a modulatory effect of the suprachiasmatic nucleus on pinealocyte discharges as well as somatosensory afferents to the gland by way of the sciatic nerve. PMID- 1922769 TI - Afferent control of central pattern generators: experimental analysis of locomotion in the decerebrate cat. AB - Changes in the motor activity of the spinal locomotor generator evoked by tonic and phasic peripheral afferent signals during fictitious locomotion of both slow and fast rhythms were analysed in the cat. The tonic afferent inflow was conditioned by the position of the hindlimb. The phasic afferent signals were imitated by electrical stimulation of hindlimb nerves. The correlation between the kinematics of hindlimb locomotor movement and sensory inflow was investigated during actual locomotion. Reliable correlations between motor activity parameters during fictitious locomotion were revealed in cases of both slow and fast "locomotor" rhythms. The main difference between these cases was that correlations "duration-intensity" were positive in the first and negative in the second case. The functional role of "locomotor" pattern dependence on tonic sensory inflow consisted of providing stability for planting the hindlimb on the ground. For any investigated afferent input the phase moments in the "locomotor" cycle were found, in which an afferent signal caused no rearrangement in locomotor generator activity. These moments corresponded to the transitions between "flexion" and "extension" phases and to the bursts of integral afferent activity observed during real locomotion. The data obtained are compared with the results previously described for the scratching generator. The character of changes in "locomotor" activity in response to tonic and phasic sensory signals was similar to that of such changes in "scratching" rhythm in the case of fast "locomotion". Intensification of the "flexion" phase caused by phasic high intensity stimulation of cutaneous afferents during low "locomotor" rhythm was changed to inhibition (such as observed during "scratching") when this rhythm was fast. It is concluded that the main regularities of peripheral afferent control for both the locomotor and scratching generators are the same. Moreover, these central pattern generators are just working regimes of a general spinal motor optimal control system containing the intrinsic model of limb movement dynamics. The consequences of this concept and ways of further research are discussed. PMID- 1922770 TI - Anterograde horseradish peroxidase tracing and immunohistochemistry of trigeminal ganglion tooth pulp neurons after dental nerve lesions in the rat. AB - The peripheral reorganization of pulpal nerves after tooth injury was studied, in the rat, with anterograde horseradish peroxidase tracing techniques, and combined retrograde Fluorogold tracing and immunohistochemistry was employed to examine the effects of inferior alveolar nerve lesions or tooth injury on some cytochemical characteristics of pulpal trigeminal ganglion nerve cells, namely content of substance P, calcitonin gene-related peptide and the ganglioside GM1 (binding subunit of cholera toxin), as well as affinity to RT 97 (antibody to neurofilament protein) and the lectin Griffonia simplicifolia isolectin I-B4. Anterograde horseradish peroxidase tracing demonstrated that pulpal nerves either disappear or reinnervate novel targets after loss of pulpal tissue. There were no obvious signs of neuroma formation. Retrograde Fluorogold labelling with immunohistochemistry showed that after inferior alveolar nerve lesions with subsequent regeneration, a much higher proportion of Fluorogold cells (15%) were substance P-positive compared to normal (2%). In addition, 3% of the cells were Griffonia simplicifolia isolectin I-B4-positive. Such cells were very rare in controls. Proportions of calcitonin gene-related peptide-, GM1- and RT-97 positive cells were normal. After tooth lesions, the proportions of Fluorogold positive substance P-, Griffonia simplicifolia isolectin I-B4-, GM1- and RT 97 labelled cells were similar to controls, while the proportion of calcitonin gene related peptide-positive neurons was reduced. The results show that pulpal deafferentation may change the long-term cytochemical characteristics of affected trigeminal ganglion neurons. PMID- 1922771 TI - Parallel development of excitotoxic vulnerability to N-methyl-D-aspartate and kainate in dispersed cultures of the rat cerebral cortex. AB - The development of excitotoxic cell death caused by L-glutamate, N-methyl-D aspartate, quinolinate and kainate was examined in dispersed primary cultures of the rat cerebral cortex. Cell death was evaluated by phase-contrast microscopy and quantified by the measurement of lactic dehydrogenase activity in the culture medium. Cells obtained from embryonic cerebral cortex on days 16-18 of pregnancy, and maintained in a serum-supplemented medium, started to respond to glutamate N methyl-D-aspartate quinolinate and kainate by cell death on day 7 in vitro. The sensitivity to the neurotoxins increased rapidly, and in a similar fashion, during the second week and remained unchanged up to day 21. Our findings indicate that, unlike the cerebral cortex in situ, the sensitivity of cultured cortical cells to the cytotoxicity mediated by N-methyl-D-aspartate and kainate receptors develops in a nearly parallel fashion. PMID- 1922772 TI - The role of the laterodorsal tegmental nucleus of the rat in experimental seizures. AB - This study determined the effects of discrete microinjections of GABA agonists in the cholinergic nuclei of the pontomesencephalic tegmentum on spontaneous behavior and seizures induced by intravenous pentylenetetrazol, bicuculline or strychnine, in the rat. Injections of both the GABAA agonist piperidine-4 sulfonic acid and the GABAB agonist (-)baclofen in the laterodorsal tegmental nucleus produced a dose-dependent suppression of behavioral arousal and a reduction in the threshold of myoclonic and clonic but not tonic seizures induced by bicuculline and pentylenetetrazol. There were no significant effects on any type of strychnine seizure. Injections in the surrounding brainstem structures, including the pedunculopontine tegmental nucleus, had little effect on spontaneous behavior and did not significantly alter the thresholds of pentylenetetrazol-induced seizures. We have previously demonstrated that injections of GABA agonists in the central medial intralaminar nucleus of the thalamus have similar effects on behavior and seizures. Since the central medial nucleus receives important direct cholinergic projections from the laterodorsal tegmental nucleus, these two nuclei form a discrete ascending system which regulates seizure threshold. PMID- 1922773 TI - Seeing faces activates three separate areas outside the occipital visual cortex in man. AB - We have examined magnetic cortical responses of 15 healthy humans to 46 different pictures of faces. At least three areas outside the occipital visual cortex appeared to be involved in processing this input, 105-560 ms after the stimulus onset. The first active area was near the occipitotemporal junction, the second in the inferior parietal lobe, and the third in the middle temporal lobe. The source in the inferior parietal lobe was also activated by other simple and complex visual stimuli. PMID- 1922774 TI - Regressive changes among corticocortical neurons projecting from the lateral suprasylvian cortex to area 18 of the kitten's visual cortex. AB - The postnatal development of corticocortical neurons projecting from the medial bank of the lateral suprasylvian cortex to area 18 of the kitten's visual cortex was examined using retrograde fluorescent tracers. Area 18 was injected in young kittens aged nine days or less and in older kittens aged 30 days or more. Many of the injected kittens were perfused with fixative four to five days later, but some of the youngest were killed after longer survival periods of 35-50 days (long-survival animals). Labelled neurons in the medial bank of the lateral suprasylvian cortex were densely distributed in both superficial layers (II and III) and deep layers (V and VI) in the kittens injected less than nine days postnatal, irrespective of whether survival was short or long, but they were found almost exclusively in layers V and VI in the old, short-survival animals. Only in the group of old kittens did we find a clear topographical arrangement of projections in the rostrocaudal direction and a correlation between the rostrocaudal lengths of the injection sites and labelled areas. In the other two groups, for a similarly sized injection site, the labelled areas were much longer rostrocaudally than in the old, short-survival kittens, and occupied roughly the posterior two-thirds of the medial bank of the lateral suprasylvian cortex, irrespective of the positions of the injections. In the frontal plane, topography was unclear in all groups. These findings demonstrate that there is considerable postnatal refinement of the projection from the medial bank of the lateral suprasylvian cortex to area 18. This involves a loss of connections originating from superficial layers and a decrease of convergence with the appearance of topography. Our results from long-survival kittens suggest that most of the early exuberant population of corticocortical neurons projecting from the medial bank of the lateral suprasylvian cortex to area 18 survive beyond the first postnatal month but undergo axonal elimination during this period. PMID- 1922775 TI - Formation of spike response to sound tones in cat auditory cortex neurons: interaction of excitatory and inhibitory effects. AB - Responses of the auditory cortical neurons to sound tones were studied extra- and intracellularly in anaesthetized cats. The pattern of response to tone stimuli could most differ in neurons tuned to the same sound frequency and forming a vertical cortical column. Phasic reactions were found in 69% of the neurons studied. Such neurons were encountered in all cortical layers but about 50% of them were localized at a depth of 0.4-1.0 mm, which corresponds to layers III and IV of the auditory cortex. Neurons with phasic reactions were able to respond to a relatively narrow frequency band that demonstrates high discriminative ability of these cells to the frequency analysis of sound signals. Inhibitory processes realized via both forward afferent and recurrent intracortical inhibition mechanisms play particular roles in the formation of phasic reaction of such neurons to different frequency tones. Twenty-six per cent of neurons generated tonic responses to the sound. The majority of such cells (94%) were localized at a depth of 1.0-2.2 mm, which corresponds to cortical layers V and VI. Inhibitory processes exert a much lesser influence on formation of tonic responses in comparison with phasic ones. Neurons of the tonic type, in contrast to phasic neurons, respond to a wider frequency band; their lower ability to discriminate sound frequency is obvious. Parameters of the responses of tonic neurons strictly correlated with the duration and intensity of the acoustic signal. The possibility of some tonic neurons playing an inhibitory role in auditory cortex is discussed [Volkov I. O. et al. (1989) Neurophysiology, Kiev 21, 498-506, 613 620 (in Russian)]. A small portion of the auditory area AI neurons (2%) demonstrated the suppression of background activity during tone stimulation. They were localized mainly in deep cortical layers (V and VI). Intracortical inhibition is supposed to play a dominant role in the formation of this type of response. About 3% of the studied auditory cortex neurons with background activity generated no response to tonic stimuli. Such cells were usually encountered in the superficial auditory cortex layers (I and II). PMID- 1922776 TI - Proliferation and differentiation of glial fibrillary acidic protein immunoreactive glial cells in organotypic slice cultures of rat hippocampus. AB - The present paper deals with the proliferation and differentiation of glial cells in organotypic slice cultures of the rat hippocampal formation. Transverse slices of hippocampus of newborn to five-day-old rats were cultivated using the roller tube technique. To study the development of glial cells under these conditions, the slice cultures were processed for immunostaining employing antibodies against the glial fibrillary acidic protein. The proliferation of glial cells was studied in double-labeling experiments employing glial fibrillary acidic protein immunostaining and the bromodeoxyuridine technique. The three-dimensional glial scaffold in the cultures was analysed in semithin and ultrathin cross-sections through the slice cultures after varying periods following explanation. Our results can be summarized as follows: 1. At all intervals after explanation of the slices there are numerous glial fibrillary acidic protein-positive cells with morphological characteristics of astrocytes. 2. With some modifications, the differentiation of astrocytes and their processes follows similar rules as observed in the hippocampus in vivo. A radial glial scaffold is also formed in the cultures. However, in cultures, a regular pattern of radial fibers is more obvious in the hippocampus proper than in the dentate gyrus. This glial scaffold persists after 20 days in vitro whereas it is known to disappear after the first postnatal week in vivo. 3. Bromodeoxyuridine-positive nuclei of glial cells were found at all time periods after explanation. After short incubation periods, they were most frequent in the "ventricular" zones of the cultures. Following longer incubation periods after bromodeoxyuridine administration, proliferating cells were found throughout the cultures, covering and underlying the cultured tissue. A rim of laterally migrating astrocytes completely surrounds the cultures. Our results demonstrate that glial cells proliferate and differentiate under the present culture conditions. After three weeks of incubation the whole slice culture is surrounded by a glial cover which may play an important role for the survival and differentiation of the cultured hippocampal neurons. PMID- 1922777 TI - Differential changes in cell size and number in topographic subdivisions of human basal nucleus in normal aging. AB - The age-related cell loss of the nucleus basalis of Meynert is of considerable importance because loss of its neurons may be followed by cognitive decline. Compared to the number found at ages 16-29 years, we found that 50% of the total population of neurons is lost by 90 years of age. This change in number is accompanied by modifications in the morphometric features, including a 17.3% increase in cell size by 60 years of age as compared with values at 16 years, and followed by a gradual decline. Topographic differences were seen both in the neuronal loss and in morphometry: in relation to the youngest group, the posterior subdivision is the most severely affected by 90 years (64.5% decrease in number and 10% reduction in neuronal size), followed by the intermediate subdivision (42% loss of neurons accompanied by 4% increase in cell size). In the anterior subdivision no significant decrease in the number of neurons could be detected, although a 15% increase in cell size occurred. PMID- 1922778 TI - Dissociable effects on spatial maze and passive avoidance acquisition and retention following AMPA- and ibotenic acid-induced excitotoxic lesions of the basal forebrain in rats: differential dependence on cholinergic neuronal loss. AB - Excitotoxic lesions of the basal forebrain were made by infusing either alpha amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or ibotenic acid. Acquisition and performance of spatial learning in the Morris water maze, over a ten day, two trials per day, training regimen were unaffected by the AMPA-induced lesions which reduced cortical choline acetyltransferase activity by 70%. However, acquisition was significantly impaired in rats with ibotenic acid induced lesions that reduced cortical choline acetyltransferase by 50%. Additionally, ibotenic acid-lesioned rats swam further than either sham or AMPA lesioned rats, in the "training" quadrant during a probe trial, in which the escape platform was removed, suggesting a perseverative search strategy. Lesions induced with AMPA, but not ibotenate, significantly impaired the acquisition of "step-through" passive avoidance. Both AMPA- and ibotenate-induced lesions significantly impaired the 96 h retention of passive avoidance, but the effect of AMPA was greater on latency measures. Histological analysis revealed that AMPA infusions destroyed more choline acetyltransferase-immunoreactive neurons than did ibotenate infusions but, unlike ibotenate, spared the overlying dorsal pallidum and also parvocellular, non-choline acetyltransferase-immunoreactive neurons in the ventral pallidal/substantia innominata region of the basal forebrain. The impairment in acquisition of the water maze following ibotenate induced basal forebrain lesions therefore appears unrelated to damage to cholinergic neurons of the nucleus basalis of Meynert and to depend instead on damage to pallidal and other neurons in this area. The AMPA- and perhaps also the ibotenate-induced impairment in the retention of passive avoidance appears to be more directly related to destruction of cholinergic neurons of the nucleus basalis. These data are discussed in the context of cortical cholinergic involvement in mnemonic processes. PMID- 1922779 TI - The anatomical substrate for cat extraocular muscle proprioception. AB - The localization of cell bodies and of the central terminal projections of extraocular muscle afferent neurons was examined in adult cats using transport of horseradish peroxidase. The results confirm that primary afferent cell somata subserving extraocular muscle proprioception are located within the medial portion of the ipsilateral trigeminal ganglion. Occasional labeling of cell bodies in the mesencephalic nucleus of the trigeminal nerve occurred only in association with evidence of spread of tracer beyond the eye muscles. These results, taken together with work of others, make it unlikely that the trigeminal mesencephalic nucleus participates significantly in eye muscle proprioception. The central projections of extraocular muscle afferent neurons were found consistently in a restricted area in the ventral portion of the pars interpolaris of the spinal trigeminal nucleus. This corresponds exactly with their site of termination in the monkey [Porter (1986) J. comp. Neurol. 247, 133-143]. Terminal labeling was restricted to this area in cases in which there was no evidence of spread of the tracer beyond the extraocular muscles. In contrast to previous findings in the monkey, the cat did not exhibit a second muscle afferent representation in the cuneate nucleus. Though it is known that extraocular muscle afferent signals interact with both retinal and vestibular signals, and thus probably are involved in both visual processing and oculomotor control, the details of their roles in these processes are not yet clear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922780 TI - Vasoactive intestinal polypeptide/peptide histidine isoleucine immunoreactive neuron systems in the basal hypothalamus of the rat with special reference to the portal vasculature: an immunohistochemical and in situ hybridization study. AB - Using immunohistochemistry and in situ hybridization, we have analysed the distribution of vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in hypothalamus of male and female Sprague-Dawley rats under normal and experimental conditions. In most cases there was a good overlap between the distribution of VIP- and PHI-immunoreactive structures. At the median eminence level precapillary arterioles along its lateral aspect were surrounded by dense networks of VIP/PHI-positive fibers, suggesting that these peptides, via their vasodilatory property, may be involved in control of blood flow through portal vessels. Furthermore, a thick VIP/PHI-containing nerve bundle of variable size was observed on the surface of the median eminence in coronal, horizontal and sagittal sections. Also this bundle could be of importance for portal circulation, but VIP/PHI released may reach the anterior pituitary level and play a role in, for example, control of prolactin release. Although different lesions were performed, the origin of the VIP/PHI nerves around lateral blood arterioles and of the bundle is still unclear, but is in all probability peripheral. Within the median eminence of untreated rats only few positive nerve endings were seen in the external layer, but after 48 h hypophysectomy a large number of PHI immunoreactive fibers could be observed. With regard to cell bodies the suprachiasmatic nucleus contained VIP/PHI-immunoreactive neurons even in untreated rats. After colchicine administration fluorescent cells were in addition seen in several other hypothalamic nuclei, including the parvocellular paraventricular nucleus. After hypophysectomy, with in situ hybridization, VIP mRNA could be demonstrated in magno- and parvocellular neurons of the paraventricular nucleus, whereas in control rats VIP mRNA was undetectable. These results demonstrate that VIP/PHI are present in at least three systems of direct neuroendocrine importance: (1) in nerves related to the blood vessels in the median eminence and presumably involved in control of blood flow through the portal system; (2) in parvocellular paraventricular neurons, presumably related to stress-induced prolactin release; and (3) in magnocellular neurons after certain experimental manipulations. PMID- 1922781 TI - Maturation of a transient outward potassium current in mouse fetal hypothalamic neurons in culture. AB - The whole-cell voltage clamp technique was used to record potassium currents in mouse fetal hypothalamic neurons developing in culture medium from days 1 to 17. The neurons were derived from fetuses of IOPS/OF1 mice on the 14th day of gestation. The mature neurons (greater than six days in culture) showed both a transient potassium current and a non-inactivating delayed rectifier potassium current. These were identified pharmacologically by using the potassium channel blockers tetraethyl ammonium chloride and 4-aminopyridine, and on the basis of their kinetics and voltage sensitivities. The delayed rectifier potassium current had a threshold of-20 mV, a slow time-course of activation, and was sustained during the voltage pulse. The 4-aminopyridine-sensitive current was transient, and was activated from a holding potential more negative (-80 mV) than that required for evoking the delayed rectifier potassium current (-40 mV). The delayed rectifier potassium current was detectable from day 1 onwards, while the transient potassium current showed a distinct developmental trend. The time constant of inactivation became faster with age in culture. The half steady-state inactivation potential showed a shift towards less negative membrane potentials with age, and the relationship was best described by a logarithmic regression equation. The developmental trend of the transient potassium current may relate functionally to the progressive morphological changes, and the appearance of synaptic connections during ontogenesis. PMID- 1922782 TI - Evidence for intrinsic expression of enkephalin-like immunoreactivity and opioid binding sites in cat superior colliculus. AB - We have investigated the cellular localization of opioid peptides and binding sites in the cat's superior colliculus by testing the effects of retinal deafferentation and intracollicular excitotoxin lesions on patterns of enkephalin like immunostaining and opiate receptor ligand binding. In normal cats, enkephalin-like immunoreactivity marks a thin tier in the most dorsal stratum griseum superficiale, small neurons of the stratum griseum superficiale, and patches of fibers in the intermediate and deeper gray layers. Eliminating crossed retinotectal afferents by contralateral eye enucleation had little immediate effect on this pattern, although chronic eye enucleation from birth did reduce immunoreactivity in the superficial layers. By contrast, fiber-sparing destruction of collicular neurons by the excitotoxins N-methyl-D-aspartate and ibotenic acid virtually eliminated enkephalin-like immunoreactivity in the neuropil of the upper stratum griseum superficiale, presumably by killing enkephalinergic cells of the superficial layers. Such lesions did not eliminate the patches of enkephalin-like immunoreactivity in the deeper layers. In normal cats, opiate receptor ligand binding is dense in the stratum griseum superficiale, particularly in its upper tier, and moderately dense in the intermediate gray layer. Contralateral eye removal had no detectable effect on the binding pattern, but excitotoxin lesions of the colliculus dramatically reduced binding in both superficial and deep layers. Some ligand binding, including part of that in the upper stratum griseum superficiale, apparently survived such lesions. Similar effects were observed in the lateral geniculate nucleus: enucleation produced no change in binding, whereas excitotoxin lesions greatly reduced specific opiate binding. We conclude that in the superficial collicular layers, both enkephalin-like opioid peptides and their membrane receptors are largely expressed by neurons of intrinsic collicular origin. The close correspondence between the location of these intrinsic opioid elements and the tier of retinal afferents terminating in the upper stratum griseum superficiale further suggests that opiatergic interneurons may modulate retinotectal transmission postsynaptically. PMID- 1922783 TI - Sensorimotor connections in the lumbar spinal cord of the young rat: a morphological study. AB - A morphological investigation of sensorimotor connections was performed on the isolated lumbar spinal cord of 8-15-day-old rats using horseradish peroxidase labelling techniques. Horseradish peroxidase was applied to the filaments of dorsal and ventral roots and injected intracellularly into motoneurons. The labelled afferent fibres and their contacts on motoneurons were examined under a light microscope. Numerous afferent collaterals entered the lateral motor nuclei. In the medial motor nuclei a few afferent collaterals were found. Some fibres were visible passing through the ventral commissure. The number of boutons per afferent collateral in the motor nuclei was 40-60. A single terminal branch contained one to five boutons (average 1.5). Predominating axodendritic and apparent axosomatic contacts were found between afferent fibres and motoneurons belonging to the lateral motor nuclei. The contacting boutons were both terminaux and en passant. As a rule, the sensorimotor connection involved dorsally and rostrocaudally directed dendrites of the first to sixth orders. PMID- 1922784 TI - Relation between structural and release parameters at the young rat sensorimotor connection. AB - The present work was carried out on isolated spinal cords of young rats. The aim of this study was the combined morphological and electrophysiological investigation of sensorimotor connections labelled with horseradish peroxidase and the evaluation of the relationship between their structural and functional properties. Sensorimotor contacts were widely distributed along the postsynaptic cell: from the soma and juxtasomatic dendrites to distal dendrites. The number of contacting boutons in the connection of a single afferent fibre and an individual motoneuron was about 10. The amplitude fluctuation patterns of the unitary and the minimal excitatory postsynaptic potentials of the motoneurons fitted with predictions based on a binomial model. A close correspondence was found between the estimated number of binomial release sites, n, and the number of contacting boutons. The calculated size of the quantal potential was about 100 microV. The difference in the organization of sensorimotor connections of the young rat and the frog is discussed. PMID- 1922785 TI - Spinal neurons in the zebrafish labeled with fluoro-gold and wheat-germ agglutinin. AB - This study concerns the identification and location of interneurons in the spinal cord of the zebrafish by way of retrograde tracing from the body musculature. To distinguish motoneurons from interneurons; two tracers were applied: the fluorochrome Fluoro-Gold to label motoneurons, and the trans-synaptically transported compound wheat-germ agglutinin to label motoneurons and the associated interneurons that are considered to be premotoneurons. Because the tracer accumulated mainly in cell bodies (not in neurites), premotoneurons labeled directly from motoneurons could not be distinguished from those labeled via interjacent cells. Both tracers were unilaterally injected into the myotomal muscle at the anal level of the animal. The number of labeled cell bodies in the spinal cord was examined 6, 10 and 16 days after injection. Several technique oriented experiments were performed in order to map all pathways along with the tracers were incorporated in the neurons. The following observations were made. (1) All Fluoro-Gold-positive cells contained wheat-germ agglutinin, but yet more cells contained only wheat-germ agglutinin; the number of wheat-germ agglutinin labeled cells was about tenfold higher than the number of Fluoro-Gold-labeled cells. (2) Fluoro-Gold labeling was restricted to cells within one to two spinal cord segments corresponding to the injection site, whereas wheat-germ agglutinin labeling was more diffuse. (3) The position and size of Fluoro-Gold-labeled cells corresponded to those of motoneurons described in previous horse-radish peroxidase experiments. (4) Statistical analysis of the group of wheat-germ agglutinin-labeled cells showed two subpopulations, one with a mean cell size and position corresponding to motoneurons and one with a smaller mean cell size, also positioned within the motor column. The smaller cells were considered to be premotoneurons. The ratio motoneuron:premotoneuron was lowest in the ventrolateral area of the motor column. PMID- 1922786 TI - Neuropeptide Y in non-sympathetic nerves of the rat: changes during maturation but not after guanethidine sympathectomy. AB - Non-sympathetic neuropeptide Y-containing nerves were demonstrated by their persistence after destruction of sympathetic nerve terminals by acute 6 hydroxydopamine treatment for 48 h. In order to examine whether these neuropeptide Y-containing nerves reinnervate tissues following the loss of sympathetic nerves we administered guanethidine sulphate to one-week-old rat pups for three weeks to produce a complete and long-lasting sympathectomy and we monitored the innervation of the superior cervical ganglion, mesenteric vein, vas deferens and urinary bladder by noradrenaline- and neuropeptide Y-containing nerves two and 16 weeks later (assay and histochemical observations). By two weeks the reduction in neuropeptide Y content of tissues was similar to the reduction after acute sympathectomy with 6-hydroxydopamine treatment, indicating that there was no early reinnervation by non-sympathetic neuropeptide Y containing nerve fibres at a time when sensory transmitters increase. Furthermore, there was no reinnervation by neuropeptide Y-containing nerve fibres by the time these sympathectomized animals had reached maturity, 16 weeks after cessation of treatment. Neuropeptide Y levels increased in the superior cervical ganglion with normal maturation but decreased in the prostatic end of the vas deferens. A non-sympathetic source of neuropeptide Y demonstrated in the immature rat vas deferens was no longer evident in the mature animal. PMID- 1922787 TI - Regulation of neurotensin content in adrenal medullary cells: comparison of PC12 cells to normal rat chromaffin cells in vitro. AB - Radioimmunoassay studies of cultures of PC12 pheochromocytoma cells have shown progressive increments in content and release of neurotensin in response to combinations of dexamethasone, nerve growth factor, activators of adenylate cyclase and lithium. We have studied the distribution of immunoreactive neurotensin by immunocytochemistry in cultures of PC12 cells and normal rat chromaffin cells, with two objectives: (i) to determine how changes measured by radioimmunoassay in extracts of PC12 cell populations are manifested at the level of individual cells and (ii) to determine whether normal chromaffin cells respond to combinations of agents similarly to PC12 cells. Staining for immunoreactive neurotensin is not identifiable in PC12 cells maintained in control medium or with any of the medium supplements alone. Approximately 3% of cells are stained after maintenance with dexamethasone plus nerve growth factor, verus 17% with dexamethasone plus nerve growth factor plus forskolin, and 33% with all four agents. This heterogeneity does not appear to result from clonal diversity, or to be cell cycle-dependent. Individual PC12 cells recruited to produce neurotensin in response to particular signals may, however, have passed a critical stage of differentiation toward a chromaffin cell, rather than neuronal phenotype before exposure to those signals. Staining for immunoreactive neurotensin is observed in up to 18% of normal chromaffin cells maintained with dexamethasone plus nerve growth factor, up to 45% with dexamethasone plus nerve growth factor plus forskolin, and up to 54% with all four agents. Proportions of cells stained under the various culture conditions are established before birth and in fetal cultures staining is confined for the most part to cells which do not undergo neuronal differentiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922788 TI - Neutrophils contribute to sympathetic nerve terminal-dependent plasma extravasation in the knee joint of the rat. AB - Infusion of bradykinin or 6-hydroxydopamine into the knee joint of the rat activates sympathetic postganglionic nerve terminals and increases plasma extravasation, a major sign of acute inflammation. Since bradykinin attracts and activates neutrophils in vivo and since neutrophils can release factors leading to plasma extravasation, we evaluated the contribution of the neutrophil to bradykinin-induced plasma extravasation. We report that perfusion of bradykinin into the rat knee joint produces a prolonged increase in plasma extravasation which is markedly reduced not only by sympathectomy (chronic pretreatment with systemic 6-hydroxydopamine) but also by depletion of circulating polymorphonuclear leukocytes (intravenous infusion of hydroxyurea combined with intraperitoneal glycogen). Depletion of polymorphonuclear leukocytes also reduced the plasma extravasation induced by intra-articular infusion of 6 hydroxydopamine, which acutely activates sympathetic postganglionic terminals. We next tested whether attraction of neutrophils into the joint, in the absence of bradykinin, was sufficient to enhance plasma extravasation. Although the classical neutrophil attractant glycogen attracted neutrophils into the knee joint, it did not increase plasma extravasation. Co-infusion of bradykinin and glycogen into the knee joint, however, provoked plasma extravasation that was significantly greater than that produced by bradykinin alone. We hypothesize, therefore, that bradykinin not only attracts neutrophils but also activates them, by an as yet undefined mechanism that requires the sympathetic terminal. The activated neutrophils release factors that lead to plasma extravasation. The next series of studies evaluated the role of the sympathetic nervous system in neutrophil attraction in vivo by bradykinin and glycogen. Since quantification of neutrophil attraction was not possible in the knee joint, we performed these studies in the peritoneal cavity, a site where neutrophils are readily attracted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922789 TI - Choline uptake in cholinergic nodose cell bodies. AB - Isolated living cell bodies were obtained by mechanical and enzymatic dissociation from adult rabbit nodose ganglion followed by separation of fibres and cells using a Percoll gradient. A purification yield of 45% was measured. Based on previous results obtained in whole ganglion and showing the presence of cholinergic cell bodies among the afferent fibres of the vagus nerve, this preparation was used to study choline uptake by neuron cell somata. Cholinergic cells counted after choline acetyltransferase immunohistological staining showed a stained population of 2.9% among the isolated population. Two [3H]choline uptake mechanisms were detected at the cell body level. The first, with Km1 = 7 microM and Vm1 = 200 pmol/h per ganglion is sodium dependent, related to acetylcholine synthesis (43%) and has an IC50 with hemicholinium-3 equal to 50 microM. The second, with Km2 = 54 microM and Vm2 = 2235 pmol/h per ganglion is sodium independent, poorly associated to acetylcholine synthesis (12%) and exhibits an IC50 of 2 microM with hemicholinium-3. Except for their sensitivity to hemicholinium-3, the high and low affinity choline uptake mechanisms observed at the somatic level have, respectively, the same characteristics as the high and low affinity mechanisms described at the synaptic level. Their physiological role, their opposed sensitivity to hemicholinium-3 compared to the synaptic uptake systems and the relation between the somatic high affinity choline transport and an acetylcholine somatic release are discussed. PMID- 1922790 TI - Reconstruction of shifting elbow joint compliant characteristics during fast and slow movements. AB - The purpose of this study was to experimentally investigate the applicability of the equilibrium-point hypothesis to the dynamics of single-joint movements. Subjects were trained to perform relatively slow (movement time 600-1000 ms) or fast (movement time 200-300 ms) single-joint elbow flexion movements against a constant extending torque bias. They were instructed to reproduce the same time pattern of central motor command for a series of movements when the external torque could slowly and unpredictably increase, decrease, or remain constant. For fast movements, the total muscle torque was calculated as a sum of external and inertial components. Analysis of the data allowed reconstruction of the elbow joint compliant characteristics at different times during execution of the learned motor command. "Virtual" trajectories of the movements, representing time varying changes in a central control parameter, were reconstructed and compared with the "actual" trajectories. For slow movements, the actual trajectories lagged behind the virtual ones. There were no consistent changes in the joint stiffness during slow movements. Similar analysis of experiments without voluntary movements demonstrated a lack of changes in the central parameters, supporting the assumption that the subjects were able to keep the same central motor command in spite of externally imposed unexpected torque perturbations. For the fast movements, the virtual trajectories were N-shaped, and the joint stiffness demonstrated a considerable increase near the middle of the movement. These findings contradict an hypothesis of monotonic joint compliant characteristic translation at a nearly constant rate during such movements. PMID- 1922791 TI - Effects of pre- and perinatal exposure to hashish extracts on the ontogeny of brain dopaminergic neurons. AB - The changes induced by maternal exposure to cannabinoids in the maturation of nigrostriatal, tuberoinfundibular and mesolimbic dopaminergic activities of rat offspring 15-40 days old were studied. In the striatum, tyrosine hydroxylase activity was constantly decreased during cannabinoid exposure in males. This decrease was correlative to increased number of D1 and D2 dopaminergic receptors. Both effects were also observed after the drug withdrawal caused by weaning on day 24. In females, the most consistent effect appeared on day 20, when decreased dopamine content and number of D1 receptors were observed. Both effects disappeared after drug withdrawal, but the reduction in the number of D1 receptors was again observed 40 days after birth. In the limbic area, cannabinoid exposure caused a decrease in the number of D1 receptors in 15-day-old females, along with decreases in the content of dopamine and its metabolite, L-3,4 dihydroxyphenylacetic acid. Changes in receptors disappeared on subsequent days, but increases in L-3,4-dihydroxyphenylacetic acid content and in its ratio with dopamine (L-3,4-dihydroxyphenylacetic acid/dopamine) were observed on day 20 followed by a decrease in the neurotransmitter content on day 30. In males, tyrosine hydroxylase activity increased on day 30, followed by an increase in L 3,4-dihydroxyphenylacetic acid content and L-3,4-dihydroxyphenylacetic acid/dopamine ratio on day 40. In the hypothalamus, the cannabinoid effects were always manifested after the cessation of drug exposure. Thus, a rise in L-3,4 dihydroxyphenylacetic acid/dopamine ratio was observed in 30-day-old females, and it was followed by a decrease on day 40, accompanied by a decrease in the anterior pituitary content of dopamine. Rise in prolactin release was not significant. In males, tyrosine hydroxylase activity was increased 30 days after birth, while L-3,4-dihydroxyphenylacetic acid content decreased. On day 40, L-3,4 dihydroxyphenylacetic acid content increased, paired to a rise in L-3,4 dihydroxyphenylacetic acid/dopamine ratio and anterior pituitary content of dopamine and to a decrease in the prolactin release. Perinatal exposure to cannabinoids altered the normal development of nigrostriatal, mesolimbic and tuberoinfundibular dopaminergic neurons, as reflected by changes in several indices of their activity. These changes were different regarding the sex and brain areas. Cannabinoid effects were more marked and constant in the striatum of males, while alterations in limbic neurons were mostly transient and those in hypothalamic neurons occurred after drug withdrawal. A long-term impact of these early changes on the neurological processes of adulthood is plausible. PMID- 1922792 TI - Comparative cognitive effects of carbamazepine and phenytoin in healthy adults. AB - We investigated neuropsychological effects of carbamazepine and phenytoin in 21 healthy adults using a randomized, double-blind, double-crossover design and treating each subject with each drug for 1 month, separated by a 1-month washout. There were neuropsychological evaluations at baseline, the end of each treatment month, and 1 month after the last treatment phase. Cognitive measures included Symbol Digit Modalities Test, Selective Reminding Test, Complex Figures, Paced Auditory Serial Addition Test, Stroop, Finger Tapping, Grooved Pegboard, Choice Reaction Time, P3 Event-Related Potential, Hopkins Symptom Checklist, and Profile of Mood States (POMS). Compared with nondrug conditions, the anticonvulsants significantly impaired Stroop, Choice Reaction Time, Grooved Pegboard, Hopkins, and POMS. Employing anticonvulsant blood levels as covariates, there were only two significant differences between drugs, one in favor of carbamazepine (ie, Finger Tapping) and one in favor of phenytoin (ie, Stroop). The results suggest that differences in cognitive effects of carbamazepine and phenytoin are not clinically significant. PMID- 1922793 TI - HLA-A2, or a closely linked gene, confers susceptibility to early-onset sporadic Alzheimer's disease in men. AB - There is a weak association between Alzheimer's disease (AD) and the histocompatibility antigen HLA-A2, suggesting that A2 has either a minor role in AD or a major role in a subtype of it. To test these alternatives, we studied 54 consecutively ascertained AD patients diagnosed by NINCDS-ADRDA criteria. Patients had a higher frequency of A2 than control subjects, primarily due to the elevated frequency of this antigen in men with early onset of dementia (less than or equal to 60 years): 92% of early-onset men had A2 as compared with 44% of controls. This finding suggests that A2, or a closely linked gene, confers susceptibility to early-onset AD in men. Furthermore, A2 appears to be primarily associated with sporadic AD, rather than with the familial subtype. PMID- 1922794 TI - Discordance and concordance of dementia of the Alzheimer type (DAT) in monozygotic twins indicate heritable and sporadic forms of Alzheimer's disease. AB - Monozygotic (MZ) twin pairs concordant for dementia of the Alzheimer type (DAT) or for proven Alzheimer's disease (AD) have a significantly higher frequency of a positive family history (DAT or AD in at least one first-degree relative, p less than 0.002) than do discordant MZ twin pairs, consistent with a lesser predicted distribution of proportions of surviving first-degree relatives without DAT (or AD) (p less than 0.001). The results suggest that concordant MZ twin pairs with DAT (or AD) have a heritable form of disease. AD in discordant twins may result from environmental influences or from a somatic chromosomal change following zygotic division. PMID- 1922795 TI - Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis. AB - We reviewed the medical records of 821 Olmsted County residents who had suffered head trauma with presumed brain injury between 1935 and 1974 and were more than 40 years old at the time of their last medical assessment. These patients were followed over 15,000 person-years for dementia and other degenerative neurologic diseases. The standardized morbidity ratio (SMR) for dementia was 1.06, and the SMR for dementia of the Alzheimer type was 1.00. These values are not significantly elevated and are inconsistent with studies that suggest that head trauma is a risk factor for Alzheimer's disease. In addition, the SMRs for parkinsonism (1.04), Parkinson's disease (0.94), and amyotrophic lateral sclerosis (1.05) were not significantly elevated, providing no evidence that head trauma is a risk factor for these disorders. However, these latter results are based on smaller total case numbers. PMID- 1922796 TI - Sudomotor function in autonomic failure. AB - We measured sweat production to direct gland stimulation with intradermal methacholine in patients with autonomic failure and in normal subjects. The sympathetic skin response (SSR) to electrical stimulation was assessed in some of the same subjects. Patients with pure autonomic failure (PAF) and multiple system atrophy (MSA) produced significantly less sweat than controls. None of the patients manifested greater than normal sweat production. Impaired sweat gland function does not differentiate MSA and PAF. The SSR did not correlate with sweat response to methacholine. An SSR can occur in the absence of normal sweat gland function. The diminished production of sweat in response to intradermal methacholine in PAF suggests that human sweat glands do not develop chronic denervation supersensitivity. Intradermal methacholine is a simple method to assess sweat gland function. PMID- 1922797 TI - Dopamine sulfate in ventricular cerebrospinal fluid and motor function in Parkinson's disease. AB - We measured sequential plasma and CSF levodopa and CSF dopamine sulfate levels following a single dose of levodopa/carbidopa in two patients with advanced Parkinson's disease (PD). We obtained CSF from an Ommaya reservoir implanted in the lateral ventricle several months earlier at the time of transplantation of adrenal medulla to caudate nucleus and could detect dopamine only in its sulfconjugated form. Peak CSF levodopa and dopamine sulfate levels occurred 1 to 1.5 hours after peak plasma concentration of levodopa. The time course of clinical improvement and worsening correlated precisely with the appearance and disappearance of both levodopa and dopamine sulfate in the CSF. The precise correlation between CSF dopamine sulfate and levodopa indicates that in patients with advanced PD the brain retains some capacity to convert levodopa to dopamine. The transient nature of the correlation between motor fluctuations, CSF levodopa, and CSF dopamine sulfate is consistent with suggestions that in patients with advanced PD there is a diminished capacity to store dopamine synthesized from exogenous levodopa. Dopamine sulfate appears to be a useful index of the availability of dopamine in the parkinsonian brain. PMID- 1922798 TI - Central nervous system abnormalities in Lyme neuroborreliosis. AB - Intrathecal production of anti-Borrelia burgdorferi antibody occurs frequently in CNS Lyme, yet reliable diagnosis of neuroborreliosis is still considered difficult and controversial. Therefore, we assessed the utility of this measurement in 103 Lyme patients. Among 15 patients with Lyme meningoradiculitis and 41 controls, diagnostic specificity was 93% and sensitivity 87%. Application of this method permits the identification of a rare B burgdorferi-associated multifocal encephalitis (brain infection) and its differentiation from a milder encephalopathy, or confusional state; the latter may not require CNS bacterial invasion. The encephalitis involves white matter more often than gray; severity varies widely. Of six patients with this antibiotic-responsive encephalitis, five were positive for HLA DQw3(DQw7). We conclude that (1) measurement of intrathecal antibody production is a reliable indicator of CNS infection, (2) North American neuroborreliosis includes the same spectrum of neurologic dysfunction as described in Europe, and (3) HLA typing may be useful in furthering our understanding of severe CNS involvement. PMID- 1922799 TI - Autoantibodies to GABAergic neurons and response to plasmapheresis in stiff-man syndrome. AB - Stiff-man syndrome is a rare disorder of unknown etiology in which progressive rigidity, spasms, and continuous motor unit activity may be due to dysfunction of GABAergic inhibition of alpha motor neurons. Some patients with this disorder have evidence of autoantibodies reactive with glutamic acid decarboxylase (GAD). We describe a patient with progressive stiff-man syndrome and high titers of GAD like immunoreactivity in serum but not spinal fluid. Plasmapheresis resulted in lowered antibody titers, decreased exteroceptive reflex responses, reduced motor unit activity, and marked clinical improvement. Immunohistochemistry using patient serum and plasma produced specific labeling of human and experimental animal tissue consistent with GABAergic neurons and terminal fields. This antibody response was not present in samples from more than 200 other patients. These results provide additional evidence of an autoimmune mechanism for stiff man syndrome and indicate plasmapheresis may be beneficial in some patients. PMID- 1922800 TI - Progressive supranuclear palsy: loss of choline-acetyltransferase-like immunoreactive neurons in the pontine reticular formation. AB - We performed a quantitative immunocytochemical study using a polyclonal antibody directed against choline acetyltransferase (ChAT) in the lower pontine reticular formation in four control subjects and three patients with progressive supranuclear palsy (PSP). In the normal brains, there was detectable ChAT-like immunoreactivity in the nucleus papillioformis, a precerebellar reticular nucleus, and in the nucleus pontis centralis caudalis. In PSP patients, the mean estimated total number of ChAT-like immunoreactive cells was 54% of controls in nucleus papillioformis and 40% of controls in nucleus pontis centralis caudalis. The demonstration of ChAT-like immunoreactivity in nucleus papillioformis is consistent with studies suggesting an extrinsic cholinergic innervation of the cerebellar cortex. Loss of cholinergic cells in nucleus pontis centralis caudalis that corresponds largely to the paramedian pontine reticular formation may be related to disturbances of horizontal saccades in PSP patients. PMID- 1922801 TI - A multi-center, double-blind study on slow-release bromocriptine in the treatment of Parkinson's disease. AB - We report on the clinical efficacy of a slow-release formulation of bromocriptine studied in a multi-center, double-blind trial using standard bromocriptine as the control. We randomly allocated enrolled patients (N = 243) to either the slow release or normal bromocriptine group. Sixty of them were de novo patients. The maintenance dose of slow-release bromocriptine was 14.2 +/- 0.7 mg/d and that of standard bromocriptine 13.5 +/- 0.7 mg/d (mean +/- SE). The slow-release formulation was taken twice and the standard three times a day. Forty-one percent of the patients treated with the slow-release bromocriptine and 32% of the patients treated with the standard bromocriptine showed moderate or marked improvement in the global improvement rating. There were no serious side effects, and the frequency of vomiting and epigastric discomfort was lower in the patients treated with the slow-release bromocriptine. Clinical efficacies for tremor, rigidity, akinesia, and gait disturbance were comparable between the two drugs tested. The slow-release bromocriptine seems to be a valuable drug for the treatment of Parkinson's disease with less severe side effects than regular bromocriptine. PMID- 1922802 TI - Fatigue and myalgia in AIDS patients. AB - Fatigue and myalgia are common in patients with acquired immunodeficiency syndrome (AIDS). To determine whether altered muscle metabolism or impaired activation of muscle might account for these symptoms, we utilized three different exercise protocols to produce fatigue in nine AIDS patients who complained of both fatigue and exercise-exacerbated myalgia. Five were taking azidothymidine (AZT), which may cause a mitochondrial myopathy. Simultaneous measures of force, EMG, and muscle metabolites (phosphocreatine, inorganic phosphate, adenosine triphosphate, and intracellular pH) using phosphorus nuclear magnetic resonance spectroscopy were performed during fatigue and recovery. There were no significant differences between patients and controls in terms of fatigability, muscle metabolism, or muscle activation. These results provide no support for the hypothesis that fatigue or myalgia in AIDS patients derives from altered muscle metabolism or that AZT produces mitochondrial myopathy. PMID- 1922803 TI - Computerized and conventional neuropsychological assessment of HIV-1-infected homosexual men. AB - We administered a battery of computerized and conventional neuropsychological measures to a group of 507 HIV-1 seronegative, 439 asymptomatic HIV-1 seropositive (Centers for Disease Control [CDC] groups 2 and 3), and 47 symptomatic HIV-1 seropositive (CDC group 4) homosexual/bisexual men enrolled in the Los Angeles center of the Multicenter AIDS Cohort Study. Tasks included multiple measures of attention, reaction time, memory, and psychomotor speed. Comparison of group means revealed significant differences in performance between HIV-1 seronegative and symptomatic HIV-1 seropositive men on computerized measures of choice reaction time and on conventional measures of memory and motor speed. These findings are consistent with previous research in this area and support the sensitivity of both computerized and conventional neuropsychological instruments for detecting cognitive changes found in symptomatic HIV-1-infected individuals. Asymptomatic seropositive men, on the other hand, did not differ significantly from seronegative subjects on any of the computerized or conventional neuropsychological measures. Only 13% of the asymptomatic HIV-1 seropositive men showed abnormal performance on a composite measure of cognitive functioning from the computerized test battery. This proportion did not differ significantly from that of seronegative controls (14%), but was significantly lower than the percentage of abnormal findings observed among symptomatic HIV-1 seropositive subjects (28%). Thus, results from this study support the hypothesis that the frequency of neuropsychological abnormalities in asymptomatic HIV-1 infected homosexual men is low and not statistically different from that of seronegative controls. PMID- 1922804 TI - Sleep-wake cycles in multi-infarct dementia and dementia of the Alzheimer type. AB - We monitored by actigraphs minute-by-minute activity of 10 patients with multi infarct dementia (MID), 15 patients with dementia of the Alzheimer type (DAT), and 11 control volunteers for eight consecutive 24-hour periods to assess sleep wake cycles and sleep quality. MID patients had disrupted sleep-wake cycles associated with decreased sleep quality. In contrast, ambulatory DAT patients maintained a relatively normal sleep-wake cycle that did not differ significantly from controls. There was no correlation between the severity of intellectual deterioration and the degree of sleep-wake cycle disintegration in either group of dementia patients. PMID- 1922805 TI - Sentence comprehension and praxis deficits in Parkinson's disease. AB - We evaluated the ability of nondemented patients with idiopathic Parkinson's disease (PD) to interpret various aspects of sentences and to perform learned limb and oral gestures. The patients were significantly compromised in their ability to answer simple questions about sentences such as "The eagle chased the hawk that was fast. Which bird was chased?" A discriminant analysis revealed that up to 73% of PD patients differ from control subjects in their ability to perform this task. Patients with PD were also significantly compromised in their gestural performance, and a discriminant analysis indicated that a praxis deficit may be evident in up to 64% of patients. We conclude that language and gestural processing impairments are frequent in patients with PD. PMID- 1922806 TI - Cerebrospinal fluid methylmalonic acid levels in normal subjects and patients with cobalamin deficiency. AB - We measured methylmalonic acid, which accumulates in the blood and tissues of patients with cobalamin deficiency, in the CSF of 65 patients using capillary-gas chromatography and mass spectrometry. In 58 control patients, methylmalonic acid concentrations were always higher in CSF than in serum (mean CSF: serum ratio, 2.65; range, 1.17 to 7.78). In contrast, in six patients with elevated serum methylmalonic acid levels due to renal failure, CSF concentrations were normal in five and the CSF: serum ratio was less than one in four. In three patients with neuropsychiatric syndromes due to cobalamin deficiency and one patient with a normal serum cobalamin level who was an abuser of nitrous oxide, CSF concentrations were markedly increased (mean level, 600 times that of controls), out of proportion to those in the serum (mean CSF: serum ratio, 8.38; range, 3.5 to 13.5). The potential usefulness of CSF metabolite levels in the diagnosis of cobalamin deficiency is undetermined. PMID- 1922807 TI - Unilateral occipital lesion causing hemianopia affects the acoustic saccadic programming. AB - Infrared oculographic recordings of saccades evoked by auditory or visual targets in four patients with hemianopia due to an occipital lesion showed that these patients employed a different strategy to find visual and auditory targets in each hemifield. In the seeing hemifield, the patients acquired auditory targets with both monosaccadic and multiple saccadic refixations. The first saccade, the largest, brought the eyes toward the target; the following smaller saccades completed the search as in normal subjects. Saccades to visual targets consisted of one orthometric saccade or two saccades. By contrast, in the blind hemifield the patients acquired auditory targets by a staircase strategy consisting of stepwise saccadic search movements similar to those used for visual targets in the same hemifield. The similarity of strategy to auditory and visual targets suggests a common motor program controlled by the visual input. The latency, accuracy, and velocities of visual and acoustic responses were equal in both hemifields. PMID- 1922808 TI - The clinical features and prognosis of pseudoseizures diagnosed using video-EEG telemetry. AB - A total of 110 patients underwent diagnostic evaluation for attacks of uncertain origin by means of video-EEG telemetry and had a diagnosis of pseudoseizures confirmed. Eighty-six patients (78%) were female, mean age of onset 25 years, and mean duration of attacks was 3 years. Many of the patients had erroneously been thought to be suffering from epilepsy. The attacks could be divided into two broad categories: attacks of collapse (one-third) and attacks with prominent motor activity (two-thirds). In some patients, the attacks were associated with incontinence and injury. The differential diagnosis and clinical features of the attacks are described. Additional psychiatric features were present in 52 (47%) patients. Follow-up (for a median 5 years; range, 1 to 14 years) showed that 40% of these patients stopped having pseudoseizures. This favorable outcome was associated with being female, leading an independent life, a formal psychological approach to therapy and counseling, and the absence of coexisting epilepsy, but not with the duration of pseudoepilepsy, prior episodes of pseudostatus, the coexistence of overt psychiatric disease, or the clinical features of the attacks. PMID- 1922809 TI - Allele-specific sequencing confirms novel prion gene polymorphism in Creutzfeldt Jakob disease. AB - We analyzed the prion protein coding sequence in a familial Creutzfeldt-Jakob disease patient who did not have any of the currently recognized prion protein mutations. Denaturing gradient gel electrophoresis indicated that the prion protein coding sequence was heterozygous at least one location. We isolated each allele by denaturing gradient gel electrophoresis and directly sequenced. We found a DNA polymorphism at codon 178 that predicted the amino acid substitution, aspartate----asparagine. Whether this represents a benign polymorphism or pathogenic mutation will depend on analysis of the functional consequences of this change. Denaturing gradient gel electrophoresis and allele-specific sequencing proved to be efficient means of analyzing sequence polymorphisms in this gene. PMID- 1922810 TI - Localization of idiopathic generalized epilepsy on chromosome 6p in families of juvenile myoclonic epilepsy patients. AB - Juvenile myoclonic epilepsy (JME) is a distinct subform of idiopathic generalized epilepsy of adolescence. Linkage studies with Bf and serologic HLA markers in families of JME patients have shown a tight linkage on chromosome 6. We present a linkage analysis with HLA-DQ restriction fragment length polymorphisms on more extended families, paying particular attention to the epilepsy type of the affected family members. We studied 21 families of JME patients with a total of 143 family members and obtained a highest logarithm of the odds (lod) score of 3.9 (theta m = 0.01, theta f = 0.01) assuming a dominant mode of inheritance and 70% penetrance when family members with JME, absence epilepsy, or epilepsy with generalized tonic-clonic seizures (GTCS) were considered as affected. When we also classified clinically normal family members with generalized spike-wave discharges in the EEG as "affected," the maximum lod score was 4.1 (theta m = 0.01, theta f = 0.3) under a dominant mode of inheritance and 90% penetrance. These findings support the conclusion that a gene locus for a group of idiopathic generalized epilepsies (JME, epilepsy with absences, and epilepsy with GTCS) maps to chromosome 6p. PMID- 1922811 TI - Diffuse cortical dysplasia, or the 'double cortex' syndrome: the clinical and epileptic spectrum in 10 patients. AB - Diffuse neuronal migration disorders associated with epilepsy can now be recognized by modern neuroimaging techniques, particularly high-resolution MRI. We report 10 patients with a recently described MRI picture of continuous or generalized band heterotopia underlying the cortical mantle, giving the appearance of a "double cortex." They have epilepsy, and almost all have mental retardation. The epileptic disorder varies in nature and degree of severity. Patients may present with infantile spasms, a Lennox-Gastaut syndrome, or other forms of secondary generalized or multifocal epilepsy. Response to medical treatment is variable. Callosotomy may lead to considerable reduction of drop attacks, present in 60%. Mental retardation is usually mild or moderate, and only rarely severe. It correlates with the type of epileptic syndrome, and is greater in patients with more disorganized cortex overlying the heterotopia. Recognition of this entity by MRI is important for appropriate diagnosis of the epileptic disorder, planning of therapeutic strategy, and prognosis. PMID- 1922812 TI - Widespread tissue distribution of a tRNALeu(UUR) mutation in the mitochondrial DNA of a patient with MELAS syndrome. PMID- 1922813 TI - Death rates from Parkinson's disease in Norway reflect increased survival. PMID- 1922814 TI - High prevalence of migraine in a high-altitude population. PMID- 1922815 TI - Cocaine as a risk factor for acute dystonic reactions. PMID- 1922816 TI - Recurrent syncope as the presenting symptom of Arnold-Chiari malformation. PMID- 1922817 TI - Inability to sneeze as a manifestation of medullary neoplasm. AB - A young man with headache was unable to sneeze despite a strong sensory urge to do so. Magnetic resonance imaging revealed a cystic neoplasm in the medulla oblongata that presumably interrupted the efferent arc of the sneezing reflex. PMID- 1922818 TI - Ear click in palatal tremor: its origin and treatment with botulinum toxin. AB - We report the successful treatment of a rhythmic, continuing ear click in a patient with palatal tremor with local injections of botulinum toxin into the tensor veli palatini muscle. We could demonstrate that the ear click occurred during contraction of the tensor veli palatini, which opens the eustachian tube. Therefore, we believe that the clicking noise is due to the sudden breakdown of the surface tension within the eustachian tube. Our observations suggest that the ear click is due to rhythmic discharges of the trigeminal nucleus rather than the ambiguous nucleus. PMID- 1922819 TI - Superior oblique myokymia: quantitative description of the eye movement. AB - We studied superior oblique myokymia (intermittent uniocular microtremor) using magnetic scleral search coils. The monocular disorder consisted of both phasic and tonic components consistent with the primary, secondary, and tertiary actions of the superior oblique muscle. These observations support the hypothesis of a disorder restricted to the superior oblique motor unit. PMID- 1922820 TI - Coexistence of Lambert-Eaton myasthenic syndrome and subacute cerebellar degeneration: differential effects of treatment. AB - A 61-year-old woman presented with two paraneoplastic neurologic disorders- Lambert-Eaton myasthenic syndrome (LEMS) and subacute cerebellar degeneration (SCD)--that antedated the diagnosis of small-cell carcinoma of the lung by 15 months. Plasmapheresis initiated before the identification of the tumor had a beneficial effect on LEMS but did not affect the SCD. Chemotherapy administered for treatment of the primary tumor was also associated with improvement of LEMS but, like plasmapheresis, had no effect on SCD. While the pathogenesis of both LEMS and SCD is thought to be mediated predominantly by humoral immune factors, a differential therapeutic response indicates that mechanisms of tissue damage or susceptibility to tissue injury, or both, differ in these two disorders. PMID- 1922821 TI - A case of C2 herpes zoster with delayed bilateral pontine infarction. PMID- 1922822 TI - Absence of association of HTLV-I infection with type 1 neurofibromatosis in the United States or Japan. AB - An HTLV-I tax transgenic mouse model develops a syndrome with similarities to type 1 neurofibromatosis (NF-1). To investigate possible associations between this human retrovirus and NF-1, we have analyzed 67 neurofibromas from Japan (where HTLV-I infection is endemic) and compared them with 21 cases from the United States. We were not able to identify virus in tumor tissue in either group. This suggests that HTLV-I infection is not commonly associated with NF-1. PMID- 1922823 TI - Primary carnitine deficiency: heterozygote and intrafamilial phenotypic variation. AB - Two boys from different families had primary carnitine deficiency: one had cardiomyopathy and myopathy, and the other had hypoglycemia and myopathy but no cardiomyopathy. Uptake of carnitine by cultured fibroblasts was negligible in both patients. Vmax for carnitine transport was reduced to 50% of controls' value in the parents and one brother (who had hypertrophic cardiomyopathy) of the first patient. A brother of the second non-cardiopathic patient died at an early age with autopsy findings of a dilated cardiomyopathy and low cardiac carnitine. Autosomal recessive primary carnitine deficiency can express a variable phenotype in different families as well as within the same family. Heterozygotes can manifest heart involvement. PMID- 1922824 TI - Preretinal bleeding due to pontine hemorrhage. PMID- 1922825 TI - Wegener's granulomatosis mimicking temporal arteritis. PMID- 1922826 TI - Wallenberg's syndrome following self-induced manipulation. PMID- 1922827 TI - Vertebral artery occlusion and stroke from cervical self-manipulation. PMID- 1922828 TI - Acute disseminated encephalomyelitis progressing to hemorrhagic encephalitis. PMID- 1922829 TI - Central retinal artery occlusion in giant cell arteritis: treatment with nitroglycerin. PMID- 1922830 TI - Clozapine is beneficial for psychosis in Parkinson's disease. PMID- 1922831 TI - Neuromythology IX and DATATOP. PMID- 1922832 TI - Delayed-onset dystonia. PMID- 1922833 TI - Human experimentation. PMID- 1922834 TI - Basilar migraine. PMID- 1922835 TI - Steroids and muscular dystrophy. PMID- 1922836 TI - Alexia without agraphia. PMID- 1922837 TI - L-dopa in Parkinson's disease. PMID- 1922838 TI - Medical units: who should command? More reader comments. PMID- 1922839 TI - The doctors Mayo and military medicine. PMID- 1922840 TI - Chemical-biological warfare: medical logistics and defense. AB - In this article, the authors discuss some of the hard realities of chemical and biological warfare defense in terms of the medical and medical logistics implications. In the opinion of the authors, there are no adequate defensive measures at present which would protect troops and sailors from the effects of either chemical or biological warfare tactics. An overview of the current world situation is presented, as well as some of the clinical and logistical responses to chem-bio war. The effectiveness of vaccinations or other medical approaches to protecting service members from chem-bio attacks is questioned in light of the technology and of the unpredictability in guessing the agent's strain or nature (e.g. viral, bacterial, or chemical). An analysis of Mission Oriented Protective Posture gear, gas masks, and other potential external protection devices reveals them to be inadequate, impractical, or expensive. In short, whether facing known war arsenals or unknown terrorist possibilities, the armed forces of the United States when meeting chemical or biological agents will be hard-pressed to protect and heal themselves, much less the nation's civilian population. PMID- 1922841 TI - Administrative management of the soldier with seizures. AB - Based on improvement in our understanding of the prognosis of young adults with new onset seizures, and cumulative experience with the rules in effect for the last 30 years, a substantial change in the regulations affecting the fitness and profiling of these soldiers has been made. In general, these liberalize retention and profiling, set limits on the duration of trials of duty, provide for fitness determinations in soldiers with pseudo-seizures, and specify when neurologic consultation is required. PMID- 1922842 TI - Treatment of cyanide poisoning. AB - The object of this study was to evaluate the effectiveness of five regimens in treating cyanide poisoning. A series of anesthetized adult beagle dogs were instrumented to record hemodynamic and respiratory function and given 2.5 mg/kg sodium cyanide intravenously. The 10 control animals given only cyanide died at from 5 to 7 minutes. Therapy, as described below, was given to other groups at from 2 to 3 minutes following the cyanide administration. Artificial respiration did not alter the lethal effects of cyanide nor prolong survival time in any of the 10 animals. Amyl nitrite given by inhalation or by the intravenous route allowed survival of all 15 animals. Sodium nitrite (20 mg/kg), dimethylaminophenol (DMAP) (5 mg/kg), and hydroxylamine hydrochloride (5 mg/kg) given intravenously with no artificial ventilation also allowed for 100% survival (15 animals). Amyl nitrite, sodium nitrite, and sodium thiosulfate were ineffective when given intramuscularly (I.M.) (0 of 12 dogs); however, I.M. DMAP (5 mg/kg) and I.M. hydroxylamine hydrochloride (50 mg/kg) increased heart rate and blood pressure and restored spontaneous breathing. All 15 animals treated with I.M. doses of either of these drugs survived the lethal dose of cyanide. Results of these studies indicate that intravenous sodium nitrite, DMAP, and hydroxylamine hydrochloride, and amyl nitrite by inhalation, are all effective in reversing the lethal effects of cyanide poisoning. Only DMAP and hydroxylamine hydrochloride are effective when given by the intramuscular route. These results provide data to support an approach to therapy that is more practical and applicable where expert medical care may not be available following cyanide exposure. PMID- 1922843 TI - The epidemiology of tuberculosis in the U.S. Air Force, 1987. AB - In preparation for a major revision of the Air Force tuberculosis (TB) prevention and control program, we reviewed tuberculosis cases treated at Air Force hospitals and the U.S. Air Force tuberculin skin testing program for 1987. The highest rates of active TB cases and infection were observed in the Pacific overseas region. Active tuberculosis cases occurred most frequently in white male retirees and in Asian dependent females. Nineteen cases (9% of total TB cases) occurred in children under the age of 5. Only 46-60% of individuals with a positive Purified Protein Derivative-Tuberculin were placed on isoniazid (INH) chemoprophylaxis. Flying status personnel were less likely to have either active disease or TB infection than non-flying active duty members. Based upon these findings, Air Force tuberculosis prevention and control program efforts should de emphasize screening of low risk active duty populations and stress timely reporting and case finding, compliance with therapy, and initiation of INH chemoprophylaxis in accordance with existing guidelines. Young children who are contacts of active TB cases should receive special emphasis. PMID- 1922844 TI - A comparison of median hearing thresholds from U.S. Navy and U.S. Army audiometric data bases. AB - This study examined 1984 monitoring audiometric data from U.S. Navy (military and civilian) employees whose workplace required a mandatory hearing conservation program. Median hearing thresholds were compared in U.S. Navy employees, U.S. Army employees also monitored by a hearing conservation program, and a standard population from the First National Health and Nutrition Survey. Age group and frequency-specific comparisons were included. Results at 4 kHz and 6 kHz demonstrated higher median thresholds in the Navy populations that were significantly higher by clinical and statistical criteria. Possible reasons for the differences are given. PMID- 1922845 TI - PHS commissioned officers and EPA: a natural coalition for environmental quality and public health. AB - Commissioned officers of the U.S. Public Health Service play a vital role in enabling EPA to achieve its objectives and responsibilities to protect the environment and the health of the country. Of the 220 officers currently (as of April 1990) detailed to EPA, most are in the engineer category. Table III lists, by category, the PHS officers on detail to EPA. Table IV lists the approximate distribution of officers among various geographical assignments at EPA. PMID- 1922846 TI - Clinical features of young adult Hispanic psychiatric in-patients: the so-called "Puerto Rican syndrome". AB - Among 118 young Hispanic (101 Puerto Rican) psychiatric inpatients, somatic complaints, violence, suicidal tendency, hallucinations, sudden onset of symptoms, and dissociative behavior each occurred in 46% or more of patients. There was no difference in clinical presentation between island Puerto Rican patients and Puerto Rican patients raised on the mainland. There was no relationship between these behaviors and any specific psychiatric disorder. Although there is a suggestion that more of these behaviors may occur among Puerto Rican Hispanics, further study with larger control groups is needed. PMID- 1922847 TI - Predicting personality disorder diagnoses of hospitalized Navy personnel. AB - The study examined the relationship between type of non-psychotic diagnosis at time of hospitalization, pre-Navy non-psychotic condition, and paygrade for active duty, enlisted Navy personnel. The sample (N = 27,210) consisted of all hospitalized cases of active duty, enlisted Navy personnel from 1981 through 1984 with a nonpsychotic mental disorder as the primary diagnosis. Results indicated that personality disorders were more likely than other nonpsychotic diagnoses to be associated with a pre-Navy nonpsychotic condition and lower paygrades. More specifically, the strong relationship between a personality disorder diagnosis and a pre-Navy nonpsychotic condition was demonstrated only for paygrades E-1 through E-4. PMID- 1922848 TI - Predictors of general well being among Army wives. AB - Predictors of general well being were examined in a sample of Army wives who participated in the second and third iterations of the Unit Manning System Family Health Study. Nine variables measured at time 1 (including social supports, personality, domains of life satisfaction, and military life stress) and two aspects of husbands' duty schedule measured at time 2 were regressed on general well being (GWB) measured at time 2. Significant predictors of GWB at time 2 included GWB at time 1, personality, and predictability of husband's schedule at time 2. When GWB at time 1 was excluded from the model, other significant predictors emerged, including financial satisfaction, marital satisfaction, and number of days in the past 6 months that husband was away in the field. PMID- 1922849 TI - Chlamydial antigen testing on female patients presenting to the emergency department. AB - We prospectively determined the prevalence of Chlamydia trachomatis infection in patients presenting to an emergency department over a 4-month period who received pelvic exams. We compared the percentage of cases of Chlamydia diagnosed by the Chlamydiazyme immunoassay with the percentage diagnosed clinically by emergency physicians. Over the study period, 326 pelvic exams were performed. Of 36 patients (11%) with positive tests, 16 (44%) were treated clinically for pelvic inflammatory disease. Twenty (56%) received neither appropriate antibiotic treatment nor a gynecology referral based on clinical exam alone. We statistically evaluated the data using the hypothesis test for two proportions from one group. The difference was significant (Z = 4.6, p less than 0.001). PMID- 1922850 TI - When to use mesh in inguinal hernia repair. AB - With people living longer today, averaging 73 years old, the type of patients with inguinal hernias are different than in the past. At the present time, to avoid the high incidence of recurrence due to the aged and weakened tissue component of the groin area, we reinforce the posterior wall of the inguinal canal with Mersilene (dacron) mesh. Most surgeons agree to use a prosthetic mesh in recurrent inguinal hernia repairs. Moreover, sometimes it is necessary to use mesh in patients with connective tissue disorders like Ehlers syndrome, Marfan syndrome, and acquired absence of the posterior wall fascia transversalis. Currently, polypropylene and dacron mesh are the most satisfactory, since they are readily available and become well incorporated by connective tissue. PMID- 1922851 TI - Melanoma metastatic to breast. AB - A patient presented with an unusual case of a breast mass. History and meticulous physical examination led to the diagnosis of metastatic melanoma, which was confirmed by biopsy. The differential diagnosis of metastasis to breast is discussed. PMID- 1922852 TI - Scar sarcoidosis in pseudofolliculitis barbae. AB - A man with hilar adenopathy had smooth firm purplish papules (lupus pernio) on his face and pseudofolliculitis barbae (PFB) in his beard area. Biopsies of papules of both the lupus pernio and the PFB revealed non-caseating granulomas consistent with sarcoidosis. This is the first case report of sarcoidosis infiltrating lesions of PFB and the first of lupus pernio co-existing with scar sarcoidosis. In persons with suspected sarcoidosis, enlarged lesions of PFB are sites suitable for confirmatory biopsy. In addition, persons who develop keloid like papules within their PFB may be providing an early cutaneous clue to undiagnosed systemic sarcoidosis. PMID- 1922853 TI - Primary cardiac angiosarcoma: a review and case report. AB - Primary cardiac tumors, both benign and malignant, are rare. Approximately 25% of primary cardiac tumors are malignant, with the majority of these being sarcomas. One of the most common sarcomas is angiosarcoma. A case of primary angiosarcoma of the heart is presented which illustrates several of the features of this malignancy. The administration of systemic chemotherapy resulted in a brief stabilization of disease before progression and subsequent death occurred. Clinical signs and symptoms of cardiac tumors and diagnostic testing are discussed. Therapeutic options and efficacy of therapy are reviewed. PMID- 1922854 TI - Preoperative diagnosis of acromegaly by growth hormone-releasing factor radioimmunoassay. AB - Acromegaly was diagnosed in a 37-year-old woman with classical physical and biochemical findings; an enlarged sella on computed tomography suggested the presence of a pituitary macroadenoma. Radiologic evidence of a lung mass prompted radioimmunoassay of plasma growth hormone-releasing factor (7,500 pg/ml; normal less than 100 pg/ml). After resection of a bronchial carcinoid, which stained positive for growth hormone-releasing factor, circulating growth hormone releasing factor levels normalized. Subsequently, her clinical, biochemical, and radiologic evidence for acromegaly resolved. This case represents the first reported use of the human pancreatic growth hormone-releasing factor 1-40 radioimmunoassay to preoperatively diagnose this rare etiology of acromegaly. PMID- 1922855 TI - Professional etiquette--whatever happened to it? PMID- 1922856 TI - [Efficiency of use of resources in intensive care units in an urban area]. AB - 2710 patients were admitted during 1988 in 14 ICU of a crowded urban area. We determined OMEGA score at the end of the ICU stay. OMEGA scores the intensity of the treatment and depicts the utilisation of resources giving rise to the variable costs. 2085 patients intensively treated resulted in a higher mean OMEGA score than 625 patients only monitored, the length of ICU stay over 8th day increases the allocation of resources. This was conditioned also by the diagnosis in both groups of patients being liver transplant (OLTX) and chronic obstructive lung diseases (COLD), the most resources-consuming intensive patients and cardiovascular (CARD), and drug intoxication (TS), the least ones. The efficiency of the use of resources (i.e. use in survivors) in ICU treatment was 100% in monitored patients and ranges from 47.3% to 90.9% in intensively treated ones: medical unspecified (Mm), COLD, strokes, surgical unscheduled, cardiac arrest, OLTX, pneumonia and ARDS, pulmonary embolism, surgical scheduled, trauma, neurological diseases, TS. Intensive patients could be divided in a group with a good utilization (26.5%) of employed resources: TS, PE, CARD, SS, TR, PNM, NRL, OLTX) in a group with a mean utilisation (50-65%: CCA, strokes, SU) and finally in a group with a weak utilisation of resources (Mm and COLD). We computed also the mean loss of resources for each diagnosis that ranges from COLD (76.1 OMEGA points) to OLTX, strokes, Mm, SU, PNM, CCA, NRL, TR, CARD, SS, PE, and TS (10.2 points). The implications of these results and the possibilities of improving the utilisation of resources in ICU are discussed. PMID- 1922857 TI - [Nursing workload and nurse-patient ratio in intensive, subintensive and postintensive care units]. AB - 2710 patients were admitted during 1988 in 14 ICU of a crowded urban area. We determined nursing workload and nurse/patient ratio applying the TOSS score at the end of the 1st and 9th day of ICU stay. 1934 patients were admitted for intensive treatment, the mean nursing need was 805 min/day ranging from 744 to 946 min/24 h meaning a N/P ratio 1:1 or slightly less. 766 sub-intensive patients admitted for intensive monitoring needed 481 min/24 h of nursing (range 411-546) meaning 1:2 1:3 N/P ratio. The score at the 9th day, showed 263 post-intensive patients who needed 501 min (422 to 603 min), significantly higher than the sub intensive need. We discuss these indications according to the official guidelines on this topic stated by the Minister of Public Health. PMID- 1922858 TI - [Ventricular pre-excitation syndrome: anesthesiologic aspects]. AB - Two cases of pre-excitation syndrome are reported and the anaesthesiological management adopted is discussed. After a brief overview of the pathophysiology of the syndrome relative indications and contraindications of the main anaesthetic drugs and volatile agents are analyzed. The high incidence of perioperative atrial fibrillation, atrial flutter or supraventricular tachycardia and the importance of maintaining sinus rhythm is recalled. The task confronting the anaesthetist is to ensure an adequate level of anaesthesia during induction and maintenance while carefully selecting specific drugs associated with minor cardiovascular side effects. In the Authors' experience benzodiazepines, fentanyl, vecuronium and isoflurane have proved to be the most adequate choice for this type of patient. PMID- 1922859 TI - [The use of propofol in combination with fentanyl or buprenorphine in long duration anesthesia]. AB - Fifty patients of both sexes, aged between 37 and 60 years old and belonging to ASA classes I, II, III and IV, underwent urological surgery lasting more than two hours under general anesthesia using a continuous infusion of propofol, N2O/O2, vecuronium bromide 0.02% infusion. Patients were divided into two groups of 25, group A and group B, according to whether they received fentanyl or buprenorphine as an analgesic. Propofol and fentanyl consumption in group A were 5.43 +/- 0.7 mg/kg/hour and 10.53 +/- 1.7 micrograms/kg respectively, whereas those of propofol and buprenorphine in group B were 5.71 +/- 1.08 mg/kg/hour and 6.05 +/- 0.06 micrograms/kg; there was a statistically non-significant difference for propofol consumption (p greater than 0.005). During the induction and maintenance phases of anesthesia, hemodynamic parameters decreased significantly (p less than 0.001) in comparison to starting values in both groups, but no statistically significant differences were observed. Buprenorphine prolonged reawakening from anesthesia by a few minutes but at the same time extended postoperative analgesia by several hours, thus improving the overall quality of the immediate postoperative period. The most frequent side effect (32% in group A and 52% in group B) was sinusal bradycardia. PMID- 1922860 TI - [Post-operative analgesia with sub-arachnoid fentanyl: ventilatory effects in elderly patients]. AB - Twenty eight elderly patients scheduled for urologic surgery were randomly assigned to receive in a double blind fashion subarachnoid hyperbaric bupivacaine 15 mg with the addition of 50 micrograms (group A, n = 7), 25 micrograms (group B, n = 7), 12.5 micrograms (group C, n = 7), of fentanyl or 1 ml of saline (group D, n = 7) for a total volume of 4 ml. The pattern of breathing and the ventilatory response to CO2 were studied before 90, 150, 480 minutes after the subarachnoid injection. In group A mild pruritus and sedation occurred in 5 patients, nausea, vomiting and periodic breathing occurred in 2 patients. In group B mild pruritus and sedation were observed in 4 patients, nausea, vomiting in 2 patients. No significant changes in VE, Vt/Ti and Ti/Ttot were observed between the groups. Patients receiving 50 micrograms of fentanyl showed a slope VE/PET CO2 significantly below baseline values at 90 and 150 minutes (p less than 0.05). In this group the baseline values were restored after 480 minutes. No side effects were observed in group C and D. 25 micrograms fo fentanyl is the only dose with a significant analgesic effect without any respiratory depression. PMID- 1922861 TI - [Prevention of headache from spinal anesthesia with the use of epidural cortisone]. AB - The Authors have analysed the etiopathogenetic factors of the post-dural puncture headache. To prevent this complication they have experimented an original method: in 74 patients they have injected 1.5 mg of betamethasone (diluted in physiological solution) into the epidural space after the anaesthetic infusion. They conclude supporting the validity of this method of prevention and its safety. PMID- 1922862 TI - [Carotid thromboendarterectomy. Comparison of two anesthesiologic techniques]. AB - The authors have examined two homogeneous groups of patients suffering from "carotid stenosis", operated by TEAC with two different techniques of anaesthesia: general and local-regional (block). Neurological and cardiovascular complications have been recorded in pre and post-operative period. The results analysed statistically with the Pearson test, were homogeneous. However the authors, on the basis of their experience, prefer local-regional (block) anaesthesia for good haemodynamic stability and a better neurologic control. Moreover the block anaesthesia was better in patients. PMID- 1922863 TI - [Comparison of the efficacy of famotidine and cimetidine in in prophylaxis of Mendelson's syndrome in elective surgery]. AB - The Authors compared the effects of two H2-antagonist drugs (Famotidine and Cimetidine) on both volume and acidity of gastric secretions. Patients were assigned to three randomized groups, which received respectively: (1) Famotidine 40 mg P.O. the evening before the surgical act; (2) Cimetidine 300 mg P.O. in the same way and Cimetidine 300 mg I.M. 90 min before the induction of anaesthesia; (3) no drug with H2-antagonist effect. Compared with the control group, the treatment with Famotidine and Cimetidine decreases both volume and acidity of the gastric secretions. In the Famotidine group no patient showed pH less than 2.5 and gastric secretions volume greater than 25 ml. PMID- 1922864 TI - [Gorlin-Goltz syndrome. Observation of a case]. AB - A young girl (16 years old) came to our attention because she needed dental surgery for multiple cysts; she was affected by Gorlin-Goltz syndrome and by a partial deficit of clotting factor V. This syndrome is characterized by many alterations, some of which can interfere with a normal conduct of anesthesia, especially at intubation (prognathism, kyphoscoliosis, incomplete segmentation of cervical-thoracic vertebrae). Moreover this patient was heterozygote for factor V (it was reduced to 48%), so that she had some clotting alteration. We present therefore this case and the treatment undertaken. PMID- 1922865 TI - [Cardiac tamponade: an unusual cause. Clinical case]. AB - The Authors describe an unusual case of acute cardiac tamponade caused by fistulization in the pericardial cavity of an amebic abscess of the left lobe of the liver. The availability of echocardiography facilitated prompt diagnosis and treatment. PMID- 1922866 TI - [Secondary hyperparathyroidism in chronic renal failure. Role of subtotal parathyroidectomy]. AB - Fourteen patients with chronic renal failure and secondary hyperparathyroidism were treated by subtotal parathyroidectomy. Bone pain and hypercalcemia were the main indications to surgery respectively in 13 and 1 patients. Bone pain disappeared or was significantly reduced in 12/14 patients. Two patients had a persistent hyperparathyroidism. Serum alkaline phosphatase returned to normal in 12 patients and PTH in 11 of 12 patients with pretreatment high levels. PMID- 1922867 TI - [Immunological variations after thymic stimulation with special reference to IL2 RS in patients operated for neoplasms]. AB - The paper reports a study which was carried out to assess immunological function by assaying IL2 in cancer-operated patients treated with thymostimulin. The results of the study show that, used in normally fed, immunodepressed patients, this immunomodulator is able to normalise levels of lymphocyte subpopulations and to bring serum concentrations of IL2-RS to the levels of normoergic patients. PMID- 1922868 TI - [Efficacy of immunomodulating treatment in patients with different degrees of immunosuppression]. AB - Immunodepression is a common condition in patients undergoing elective operations and it constitutes a high risk for the onset of postoperative infective complications. The use of immunomodulatory drugs has proved useful in the prophylaxis of these complications, although the precise indications for each drug have not yet been clearly codified. The present study aimed to assess the effects of thymostimulin in patients with different degrees of immunodepression, by evaluating both the incidence of postoperative infections and the changes induced in various immunological parameters. The results obtained indicated that those subjects with the highest degree of immunodepression (hypo-anergic) benefited most from drug therapy in comparison to those with a lesser degree of immunodepression (relatively hypo-ergic). The advantages were evident in hypo anergic subjects both with regard to the frequency of early postoperative infections, and with regard to immunological parameters. On the other hand, in relatively hypo-ergic subjects, benefits were limited to the improvement of some immunological parameters. In our opinion, the use of thymostimulin is of particular use only in those subjects with marked immunodepression since the incidence of post-operative sepsis is highest in this group. PMID- 1922869 TI - [Caloric substrates in postoperative parenteral nutrition]. AB - The paper describes the carbohydrate, lipidic and nitrogen metabolism of the postoperative period which is subdivided into an early and a late phase. Since the metabolism of caloric substrates in the early postoperative period is a stress metabolism with glucose intolerance and wide protein catabolism, the authors emphasise that an insufficient caloric intake is worse than the fasting state and suggest that alternative caloric sources, such as branched chain amino acids, fatty acids and, even, ketonic bodies, should be used. PMID- 1922870 TI - [Thromboendarterectomy and angioplasty of the carotid bifurcation. Technical notes]. AB - Exceptional surgical reports of widespread atherosclerotic involvement of both internal and external carotid arteries required us to carry out an unusual surgical procedure. During a four years period an original carotid endarterectomy's technique was performed in four patients. We point on the importance of a correct external carotid endarterectomy on maintaining an effective intracranial arterial flow, especially when atherosclerotic lesions are contemporary present in the extra and intracranial internal carotid arteries. PMID- 1922871 TI - [Surgical and radiological intervention in the treatment of peripheral arteriovenous fistulas]. AB - The Authors report five examples of arteriovenous fistulas examined in the last two years. The different aetiology concerning these lesions, the most suitable diagnosis and the therapeutic tactics are examined and discussed. When they present results and considerations, they show optimism and discrete realism about results and prognosis as a consequence of technological progress and more and more common multidisciplinary approach towards this pathology. PMID- 1922872 TI - [Use of superior musculus rectus abdominis flap in the reconstruction of the thoracic wall]. AB - The paper reports the Author's experience of the use of the muscle-skin flap of the upper rectum homolateral to the abdomen in the reconstruction of defects of the anterior thoracic wall following cancer surgery or radionecrosis, and compares it to that using other flaps (lower T.R.A.M., Latissimus dorsi, etc.). The well known anatomy of the flap, which is fed by the upper epigastric artery, also requires a precise surgical technique to isolate the muscular fibres without damaging vascularisation, a fundamental requisite for the vitality of the flap itself. Equally important for the vitality of the operation is a detailed study of the skin above the flap in patients treated with radiotherapy. The common and specific (epigastric hernia) complications of this operation are also examined, together with the precautions used by the Authors to prevent their occurrence. PMID- 1922873 TI - [Diagnostic and therapeutic strategy in extrahepatic biliary lithiasis. Our experience]. AB - The paper describes the Authors' personal experience in the diagnosis and treatment of extrahepatic biliary lithiasis in 166 patients admitted to the Surgical Division of the International Evangelical Hospital. The basic tests for a correct diagnostic strategy are echotomography and ERCP in cases of jaundice and/or dilatation of the biliary tract with negative echographic results for lithiasis of the choledochus. The indications for surgery are also discussed and the new possibilities of pre- and post-operative PSTE are also taken into account. PMID- 1922874 TI - [Malignant tumors of the small intestine. Comments concerning 21 observed cases]. AB - Patients affected by malignant tumors of the small intestine observed by the Department of Clinical and Pathological Surgery at the University of Florence were studied from 1964 to 1989. The most important aspects of the disease were studied, on the one hand emphasising its low incidence and on the other the poor prognosis which accompanies it. Greater attention should be focused on these lesions in order to enable an early diagnosis to be made since this currently represents the sole possibility for carrying out an efficacious therapy. PMID- 1922875 TI - [Angiographic diagnosis of bleeding Meckel's diverticulum in remission]. AB - The paper reports a case of Meckel's bleeding diverticulum which was diagnosed preoperatively using a selective arteriography of the superior mesenteric artery. The infrequent use of this instrumental test may be due to the small number of examples reported in the literature. In conclusion, the Authors underline that selective arteriography can be used with good results even in cases with hemorrhagic complications during the remission phase. PMID- 1922876 TI - [Leiomyoblastoma of the stomach. Another case report]. AB - A further case of gastric leiomyoblastoma in a 53 year old woman is presented. Pathology, diagnosis, and therapy of this rare neoplasm are discussed. PMID- 1922877 TI - [Ogilvie syndrome. 2 clinical case reports]. AB - Acute pseudo-obstruction of the colon is an uncommon syndrome usually related to other diseases. Two patients with this syndrome are described. It is stressed that it is of paramount importance to recognize this syndrome as a high mortality is present in these patients if they are not treated in a right fashion. The treatment doesn't require surgery unless a complication, like cecum perforation, doesn't appear. PMID- 1922878 TI - [Hydatid cysts of the ovary. Description of a case]. AB - Hydatid cysts of the ovary are rare lesions usually secondary to the rupture of an hepatic cyst. They may remain asymptomatic for long periods of time and may be discovered incidentally or cause irritation or compression symptoms. The history and whole abdomen echography consent diagnosis also based on the detection of the primary lesion. A case of hydatid cyst of the ovary is reported. PMID- 1922879 TI - [Subcutaneous emphysema. A rare complication of colorectal colonoscopy]. AB - The Authors describe a case of subcutaneous emphysema following rectosigmoidoscopy in a 72 year old woman. Guidelines of preliminary conservative treatment and eventually careful surgical approach are suggested. PMID- 1922880 TI - Transmural ischaemic colitis following operation for ruptured abdominal aortic aneurysm. AB - A total of 20 patients with transmural ischaemic colitis following operation for ruptured abdominal aortic aneurysm were studied (4 retrospectively and 16 prospectively). The diagnosis was made during laparotomy in five patients and by flexible sigmoidoscopy in 15 patients. Eighteen patients underwent large bowel resection (11 left-sided hemicolectomy, 7 subtotal colectomy). None of the 20 patients survived long enough to leave the hospital. The unfavourable prognosis of transmural ischaemic colitis following emergency abdominal aortic aneurysmectomy makes an early diagnosis by routine postoperative endoscopy mandatory and questions bowel resection in these patients. PMID- 1922881 TI - Gallstone disease in women younger than 30 years. AB - The relation between symptomatic cholelithiasis in women under 30 years of age and pregnancy, obesity and oral contraceptive use was retrospectively studied. A total of 885 cholecystectomies were carried out in an English district hospital. In the age group under 30 years the female-male ratio was 9.7:1 vs 2.3:I in the total group (p less than 0.01). Gallstones were present in 39 women with a previous pregnancy and in 14 women without pregnancy. Compared to an age and sex matched control group of appendicectomies a relative risk of 1.6 was found for pregnancy related gallstone disease requiring cholecystectomy (p less than 0.05). 455 Cholecystectomies were carried out in a Dutch academic hospital. The female male ratio in the group younger than 30 years was 7.0:I vs 2.3:I in the total group (p less than 0.01). In the Dutch group more women under 30 years were operated on than in the English group: 23% vs 10% (p less than 0.001). There was no significant association between symptomatic gallstones and previous pregnancies in the Dutch group (p = 0.07). Gallstone disease occurs earlier in women than in men. There appears to be a relationship between early symptomatic cholelithiasis and pregnancy in the English group only. No relationship could be found between cholelithiasis and obesity or oral contraceptive use in either group. PMID- 1922882 TI - Prognostic scoring systems in differentiated thyroid carcinoma: which is the best? AB - The usefulness of three prognostic scoring systems in differentiated thyroid carcinoma (the TNM system, the EORTC score and the AGES index) were evaluated for use in a medium size teaching hospital. Twenty-one patients with papillary (n = 13), mixed (n = 2) and follicular tumours (n = 6) were studied. Median follow-up was over seven years (range 10-194 months). Four patients died. The TNM system gives a poor discrimination between patients with a good prognosis and those with a lethal outcome and is of little value in these tumours. The EORTC score, which is easy to calculate, gives a good prediction of survival. The best discrimination between a good and a bad prognosis was found using the more complicated AGES index for papillary tumours. Of patients with a papillary or mixed papillary carcinoma, one of the two patients with a score of four or more actually died, while all with a good index of less than 4 (13/15 of this subgroup) survived, giving the best prognostic bisection of our patient group. Even in the combined group of all differentiated thyroid carcinomas, the AGES index gives the best prognostic bisection, with 33 percent of patients in the poor prognostic group, of whom 57 percent died. This makes the AGES index the most useful prognostic scoring system. PMID- 1922883 TI - The femoro-femoral cross-over bypass. AB - From 1984 to 1990 64 patients (56 men and 8 women) with a mean age of 67.1 years (36-88 yrs.) were treated with a femoro-femoral cross-over bypass (45 primary and 19 secondary procedures). All patients had an occlusion of one iliac artery. In 26 patients there were factors that made a central reconstruction unattractive. These disorders were congestive heart failure, COPD, CVA, an age over 80 years, etc. In 19 patients an occlusion of one leg of a former aortobifemoral bypass determined the choice for cross-over bypass. Three patients died (5 per cent), two patients of the so-called redo-group (septicaemia, one patient and arteriojejunal fistula one patient), the third patient died after a primary femoro-femoral bypass (myocardial infarction). The overall patency rate after three years was 78 per cent. Especially primary cross-over bypasses showed a good outcome with a primary patency of 80 per cent and a secondary patency of 85 per cent after three years. Considering that 23 of the 45 (51 per cent) primary procedures were for treatment of critical ischaemia (stage III and IV of Fontaine), a favourable limb-salvage of 21 out of 23 (91 per cent) was obtained. The cross-over bypass can be recommended as first choice therapy for patients with a unilateral iliac artery occlusion. PMID- 1922884 TI - Local thrombolytic therapy for axillary-subclavian vein thrombosis. AB - Thrombosis of the axillary-subclavian vein can be primary and secondary. The case histories of three patients with spontaneous idiopathic thrombosis of the axillary vein are presented. Successful treatment with low-dose local streptokinase infusion could be confirmed by daily venography. Instead of weeks of heparine infusions, the patients could leave the hospital after a couple of days (range 10 to 12 days), long-term follow-up (4 months) showed no recurrence. PMID- 1922885 TI - Cardiac myxoma: the grand masquerader. AB - Cardiac myxoma is the most common primary tumor of the heart. A high suspicion of this potentially lethal disease is warranted because it may mimick a large variety of diseases. Two patients with different symptoms and signs are presented, in whom resection of the tumor was successful. Complete resection of the tumor is the only effective method of treatment. PMID- 1922886 TI - Leiomyoma of the distal oesophagus mimicking achalasia. AB - An unusual case of a patient with symptoms suggestive of oesophageal achalasia is described. Most oesophageal tumour growths causing secondary achalasia are associated with malignant tumours. This patient had a large oesophageal leiomyoma closely mimicking achalasia. Treatment consisted of oesophagectomy by laparotomy and right-sided thoracotomy. A gastric tube was constructed with a cervical oesophago-gastrostomy. The patient responded well to the treatment and left the hospital after 13 days. Five other cases of benign oesophageal tumours inducing achalasia-like symptoms could be traced. Three of these were leiomyomas. PMID- 1922887 TI - [Hyperprolactinemia]. AB - Hyperlactinemia is the most commonplace expression of hypophyseal pathology, above all in females, and is one of the most frequent causes of sexual disorders. The present study examined the etiopathogenesis of hyperprolactinemic syndromes and discusses their pathophysiology, paying special attention to neuroendocrine alterations in the presence of either prolactin-secreting adenoma or other forms of hyperprolactinemia. Their clinical manifestations are then described together with a detailed review of therapies, especially for prolactinoma. Both general opinion and the authors' personal point of view are reported regarding the indications for medical and surgical treatment for micro and macro-prolactinomas. Lastly, particular aspects are taken into consideration, such as the relationship between hyperprolactinemia and pregnancy, in the light of the most recent findings on the natural evolution of prolactinemia and the possibility of treatment using dopaminergic drugs. PMID- 1922888 TI - [Intraerythrocyte folates and leukocytic neutrophil segmentation in macrocytosis in patients with liver disease]. AB - The problem of macrocytosis above all concerns deficiences and the study of these aspects is particularly important in hepatopathic patients for therapeutic purposes. A state of deficiency can also be revealed in morphological terms by the assessment of the hypersegmentation of polymorphonucleate neutrophil leucocytes. In the group of hepatopathic patients included in the study there was no significant differences in vitamin B12 concentrations in comparison to normal values, whereas mean levels of serum folates were decreased, although still within the normal range. It is worth underlining that to evaluate vitamin B12 it is necessary to measure analogous inefficient components from a metabolic point of view and the assessment of serum folates is not important as an index of normal erythropoietic activity. To overcome this limitation, we assayed intraerythrocytic folates which are vitamin-B12-dependent and these too proved to be within the normal range. Leucocyte hypersegmentation was also excluded by evaluating the mean of PMN lobes. A clearly normal RDW was also observed in macrocytic anemia in hepatopathic patients and this may represent a further difference from hepatocytic macrocytosis. PMID- 1922889 TI - [Changes in blood levels of the pituitary-thyroid axis observed during therapy with protirelin ++ in hospitalized euthyroid patients with cerebrovascular disease]. AB - The effects of a TRH-T (protireline tartrate) treatment at a dose of 2 mg/day for 3 weeks on the serum levels of the pituitary-thyroid axis hormones, have been studied in a randomized group of 10 elderly euthyroid hospitalized patients with cerebrovascular disease. At the end of the treatment an 8.3% mean increase of serum T3 level and a 12.5% mean increase of serum FT3 level (p less than 0.02 in both cases) have been observed. At the same time a 34% mean decrease of the basal TSH (p less than 0.05) and a 26% mean decrease of the delta-TSH after TRH-test (p less than 0.025) have been noted. However, the hormone concentrations changes never exceeded the normal values. In a randomized group of 9 hospitalized untreated patients with cerebrovascular disease used as controls (matched for age and sex), no significant changes of studied hormones have been recorded. In the treated patients, one week after the withdrawal of therapy serum levels of thyroid hormones and TSH went back to the levels observed before treatment. TRH-T seems to cause these modest hormone changes by decreasing the number of TRH receptors and the activity of TSH secreting cells. Nevertheless, the presence of the normal feedback in the pituitary-thyroid axis, allows a good tolerance to such a treatment. PMID- 1922890 TI - [Imported malaria. Clinico-epidemiologic and therapeutic observations]. AB - The authors notice a prevalence of P. falciparum in eight observed cases of imported malaria and confirm the increasing polychemioresistance of plasmodium and its prophylactic and therapeutic problems. PMID- 1922891 TI - [Neurotic and depressive status related to organic pathology in patients in thermal therapy]. AB - Females and males with no psychiatric history, 25-75 years old, attending thermal facilities in Boario Terme (N = 449) and in Sangemini Terme (N = 40) were administered, on the 2nd-3rd day of their admission, a questionnaire expressly conceive in order to declare conscious motivations for thermal treatments and, in addiction, the Middlesex Hospital Questionnaire (MHQ), the Zung Self Rating Scale for Depression (ZUNG-D) and the State and Trait Anxiety Inventory (STAI), in order to detect neurotic symptoms and/or anxious or depressive complaints in this kind of population. A re-test was performed after 10 days by 73 subjects, in order to verify the impact of thermal treatments on psychoneurotic profiles. Baseline data were compared with those from normal controls and psychiatric outpatients. All statistical comparisons (probands versus matched controls; test versus re-test) were analysed by means of two-tailed Student "t" test (lever of significance: p less than 0.05). In the light of the data so obtained, subjects attending thermal facilities show a typical MHQ psychoneurotic profile, more marked in females and in subjects with gastrointestinal referred somatic disease and partially responding to thermal treatments, which supports the hypothesis that a particular form of neurosis may play a significant role in motivating request of thermal therapies. The results are largely discussed. PMID- 1922892 TI - [Tolerability to terizidone (TZ) in the treatment of pulmonary tuberculosis in dialyzed patients]. AB - Six dialysed patients affected by tuberculosis involving the respiratory apparatus were included in the study. Antimycobacterial treatment consisted of polychemiotherapeutic combinations using terizidone (TZ). The need to resort to this drug may be explained by the need to exclude normally used drugs (R/AMP, INH, SM) due to resistance, allergy or organ meiopragia. Five patients received terizidone at a dose of 600-900 mg/day for the entire course of treatment, whereas it was necessary to abandon treatment in one patient due to the onset of depressive symptoms which then rapidly regressed following the suspension of TZ therapy. The good level of tolerance demonstrated in the 5 remaining cases confirm the inclusion of this drug in the treatment of a limited number of cases of tuberculosis in dialysed patients. PMID- 1922893 TI - [Captopril in heart failure in the elderly]. AB - The paper confirms the value of captopril in a sample group of 20 elderly patients (mean age 72.9 years) affected by overall cardiac decompensation in more or less clinically evident phases. All patients were randomly selected and received ACE-inhibition treatment for six months; doses of 25 mg or 50 mg captopril were given twice a day and all other drugs were suspended except for digitalis which was used by all patients without success. During the course of the trial the most important clinical results were the reduction of systemic blood pressure due to the diminution of peripheral resistance, the reduction of postload and ventricular filling pressure, and the consequent improvement of cardiac decompensation. All elderly patients treated in this manner experienced a stable improvement in the quality of life, with a considerable reduction in the consumption of diuretics to which they are particularly vulnerable. Following a broad ranging comparison with other reports, the Authors conclude that captopril is a geriatric drug which should be used as early as possible during the phases of latent cardiac insufficiency or at the first signs of a hypertensive crisis. PMID- 1922894 TI - [Combined clinico-thermographic findings for the evaluation of a topical anti inflammatory agent. Study of cinnoxicam cream]. AB - In conformity with an integrated clinico-telethermographic protocol, the therapeutic efficacy of cinnoxam cream was evaluated in 20 patients presenting minor rheumatic pathologies or post-traumatic syndromes. The product under examination induced favourable and precocius changes in the clinical and symptomatologic-functional parameters considered. PMID- 1922895 TI - [Streptococcus mitis endocarditis. Description of a clinical case]. AB - The diagnostic iter of a case of Streptococcus mitis endocarditis is reported. Bacterial endocarditis was diagnosed in a 32-year-old patient following ultrasound cardiography and microbiological tests. The paper stresses the importance of ultrasound cardiography in the diagnosis of bacterial endocarditis. PMID- 1922896 TI - [Miller Fisher's syndrome. Clinical and experimental contribution]. AB - A 19-year-old patient with acute idiopathic polyneuritis is described. Clinically, apart from ophthalmoplegia, areflexia and ataxia, the patient presented a serious bilateral and symmetrical deficiency of the VII-IX-X cranial nerve and hypanapallesthesia of trunk and extremities. Liquor examination showed albumino-cytological dissociation with an increase in liquor IgG; encephalic CT and encephalo-medullary NMR were normal; a neurophysiological study (EMG, PEV, BAER) was indicative of the PNS problems. Combined corticosteroid and plasmaferesis treatment produced complete clinical remission after about 3 months. The primary role of PNS involvement in this clinical entity is discussed. PMID- 1922897 TI - [A case of superficial lymph node tuberculosis]. PMID- 1922898 TI - [Cardiotocographic monitoring of fetal health. Comparative evaluation of traditional and computerized methods]. AB - One hundred physiological pregnant women and 76 pathological pregnant women suffering from gestational diabetes and pregnancy-induced hypertension underwent a cardiotocographic examination during the course of routine diagnostic tests. The interpretation of cardiotocographic printouts was carried out using traditional as well as computerised methods. The outcome of these tests was then related to neonatal outcome and other parameters which contributed to defining the prognosis of pregnancy. Computerised analysis was found to provide a more reliable diagnosis in comparison to traditional methods in identifying those pregnancies with a pathological neonatal outcome. In particular, in the group of physiological pregnancies, computerised interpretation proved more reliable in 87.5% of cases in which neonatal outcome was pathological; on the contrary, traditional interpretations only revealed 37.5% of the same cases. In pathological pregnancies, automatic interpretation was also found to be more reliable in predicting the non-pathological outcomes, whereas traditional methods provided a high incidence of uncertain answers. PMID- 1922899 TI - [Cytological history of 101 patients with invasive cancer of the uterine cervix]. AB - The cytological history of 101 patients affected by cervical cancer was examined. Three different groups of patients were identified: Group I included 73 women (72.3%) who had never submitted to a cytological cervical sampling, Group II included 17 (16.9%) with an unsatisfactory cytological history and Group III included 11 (10.8%) with a satisfactory cytological history. The disease stage at the time of hospitalization was evaluated in all three groups. In group I, the diagnosis of Stage I was made in 43% of the cases while in the second and third groups, this same stage was diagnosed in 75% and 80% of the cases respectively. Three of the patients from group III presented a normal cytological history, while the other 8 had an abnormal cytological response. Sixty five percent of these 8 had not been submitted to further cytological testing briefly thereafter. From an analysis of these data, the authors attempted to identify the reasons for unsuccess which are still today related to a screening program such at that for cervical cancer. Various international proposals on the organization of a screening program are considered with particular attention given to the minimum and maximum age limits of the women selected for the screening with reference to the authors' personal experience. PMID- 1922900 TI - [Varicocele and pregnancy. Comparison of treated and untreated patients]. AB - A study was made of 209 cases of sterility due to male varicocele out of a series of 1730 infertile couples. Corrective surgery was performed in 38 cases with 8 subsequent pregnancies (21.5%). A total of 31 pregnancies were achieved in the 171 cases which did not undergo surgical treatment (18.7%). PMID- 1922901 TI - [Analysis of factors associated with very low birth weight (less than or equal to 1500 g)]. AB - In 7675 deliveries performed at the University of Messina between November 1, 1983 and October 31, 1988 we determined the incidence and obstetric factors specifically associated with the birth of very low weight infants (less than or equal to 1500 gm) (VLBW). Our purpose was to characterize these factors in order to determine what may be done to limit delivery rate of VLBW. Information obtained concerning the mothers' included socioeconomic status, age, parity, previous obstetric history, any maternal conditions affecting the pregnancy, route of delivery (vaginal or operative). The incidence of infants under 1500 gm was 1.1 per cent of live births. The etiologic analysis showed that preterm labor is more frequent cause of VLBW. In women under 17 years of age the incidence of VLBW was 5.2 per cent as opposed to 1.1 per cent in the total population. Absence of prenatal care was shown in 40.8 per cent of VLBW. The previous obstetric history reported 1 or more abortions in the 53 per cent and 1 or more perinatal deaths in 17 per cent of VLBW. The clinical implications of these results are discussed. PMID- 1922902 TI - [Incidence of ectopic pregnancy at the 1st Clinic of Obstetrics and Gynecology of Bari during the past 10 years. Clinico-statistical considerations]. AB - The Authors, in the period 1979-1988, discovered 175 ectopic pregnancies out of a total of 16.641 pregnancies: a rate of incidence of 1 in 95 (1.05%); 28 patients were fitted with an IUD. In accordance with published data, they recognize an increase in the incidence of ectopic pregnancies and emphasize the importance of a precocious clinical diagnostic, to reconcile timeliness of operation with the need of conservative surgery, the indication for which should take into account many factors (the age, the general condition, the parity, the wish for a pregnancy, the state and condition of the tube on each side) since it seems to predispose to recurrent ectopic pregnancies. They indicate the negative effects on the tube for patients fitted with an IUD. PMID- 1922903 TI - [Ectopic pregnancy. A ten-year case load of the Obstetric and Gynecologic Department of the Ospedale Civile of Taranto]. AB - The Authors report the ectopic pregnancies incidence in the period from 1-1-79 to 31-12-88 at Department of Obstetric and Gynecology of the Hospital in Taranto. The ectopic pregnancies discovered were 130 with a rate of 0.49% versus the deliveries (26,515) and of 0.18% versus all the women recovered (70,024). The Authors observed no increase in the incidence of ectopic pregnancy and stress the value of early clinical diagnosis to preserve reproductive functions in these patients. PMID- 1922904 TI - [Effects of danazol on the endometrium during peri-menopausal meno-metrorrhagia]. AB - Perimenopausal abnormal bleeding is one of the most common gynecological problems. We have assessed the effectiveness of danazol 200 mg daily for 3 months in 42 patients with perimenopausal abnormal bleeding without any previous treatment and in 23 patients previously treated with norethisterone or medroxyprogesterone acetate but with a recurrence of bleeding 2 months after the end of the treatment. In the overall population treated by danazol at the end of treatment we had: bleeding normalized in 88.2% and hysteroscopic patterns, showing regression of hyperplasia in 95% of cases. The endometrial effects were maintained 2 months after the end of treatment with an increase of the hyperplastic pictures at 4 (26%) and up to 12 months (60%). We had amenorrhea in 10% of patients at the end of treatment and in 2 cases only treatment was discontinued for severe side effects. The comparison of these better results with those obtained by progesterone agents and with those of a preliminary experience with GnRH agonists had led us to consider the importance of an additional endometrial effects exerted by danazol. Particularly the immunosuppressive properties of this drug, as we have shown in "in vitro" conditions, can determine a decreased secretion of growth factors by local immune cells which in turn can further explain the endometrial antiproliferative action of this drug. PMID- 1922905 TI - [Doppler flowmetry in a case of single umbilical artery]. AB - A case of sonographic diagnosis of single umbilical artery associated with hypoplastic left heart syndrome and left renal agenesis is reported. Umbilical artery Doppler waveforms are presented and discussed for the first time. PMID- 1922906 TI - [Plasma exchange in a case of HELLP syndrome associated with disseminated intravascular coagulation]. AB - The Authors describe a case of HELLP syndrome associated with disseminated intravascular coagulation occurred after delivery in a patient with late hypertension without any sign or symptom of preeclampsia during pregnancy. The use of plasma exchange has contributed to the recovery from the pathology. PMID- 1922907 TI - Experimental autoimmune glomerulonephritis induced by homologous and isologous glomerular basement membrane in Brown-Norway rats. AB - In order to study disease mechanisms and potential forms of therapy in glomerulonephritis, a model of experimental autoimmune glomerulonephritis (EAG) has been developed in the rat. We have examined the response of Brown-Norway (BN) rats to a single i.m. injection of collagenase-solubilised homologous (Sprague Dawley, SD) or isologous (BN) glomerular basement membrane (GBM), with and without complete Freund's adjuvant (CFA). There was a dose-dependent circulating anti-GBM antibody response to all preparations of rat GBM. Animals given either antigen alone at a dose of 2 mg/kg developed circulating anti-GBM antibodies, which reached peak values by 6 weeks (63 +/- 5% following SD GBM; 53 +/- 8% following BN GBM), but did not develop glomerular deposits of IgG or nephritis. Animals given 2 mg/kg SD GBM in CFA developed greater concentrations of anti-GBM antibody by 6 weeks (122 +/- 20%) together with linear deposits of IgG on glomerular and tubular basement membranes (TBM), albuminuria (mean 7 mg/24 h), and variable focal segmental necrotising glomerulonephritis with mild interstitial nephritis. The same dose of BN GBM in CFA produced similar concentrations of circulating antibody (144 +/- 26%), with linear deposits of IgG on GBM but rarely TBM, little albuminuria, and variable mild focal glomerulonephritis. Other strains injected with SD GBM in CFA showed a variable circulating anti-GBM antibody response, which was similar to that of BN rats in PVG and DA rats but lower in LEW and WAG rats. Linear deposits of IgG on the GBM were detected in a proportion of PVG and DA rats, but not in LEW or WAG rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1922908 TI - Abnormal glomerular and tubular response to intravenous frusemide in patients with chronic glomerulonephritis. AB - Fourteen normotensive patients with chronic glomerulonephritis and well-preserved renal function and thirteen healthy control subjects were studied. Glomerular filtration rate (GFR), proximal and distal absolute and fractional tubular reabsorption (PAR, PFR, DARNa, DFRNa), evaluated by the lithium clearance technique, were determined before and in four 30-60-min periods after intravenous injection of frusemide 0.5 mg/kg body weight (Study 1) and 1.0 mg/kg body weight (Study 2). Plasma concentrations of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP) and arginine vasopressine (AVP) were measured before, and 60 and 180 min after frusemide. GFR decreased and UNa and FENa increased significantly in patients and controls after frusemide in both studies, but in study 2 GFR decreased significantly more in patients than in controls, and UNa and FENa increased significantly less above baseline in patients compared to controls. PAR, PFR, DARNa, and DFRNa were reduced in patients and controls in both studies. In study 2 the reduction in PAR was significantly (P less than 0.05) less pronounced in patients (23%) than in controls (43%), whereas DARNa was reduced significantly more (P less than 0.05) in patients (36%) than in controls (21%). The efficiency of frusemide with regard to renal sodium excretion was significantly reduced in patients compared to controls in both studies. Angiotensin II and aldosterone increased, ANP decreased, and AVP was unchanged in patients and controls in both studies. It is concluded that in comparison to control subjects, patients with chronic glomerulonephritis and well-preserved GFR respond to frusemide with an exaggerated reduction in GFR, a lesser decrease in absolute proximal tubular reabsorption, and a larger reduction in absolute distal tubular reabsorption. Thus, primary glomerular disease with well-preserved glomerular function may be accompanied by a distinctly disturbed tubular function. PMID- 1922909 TI - Low-dose desferrioxamine test for the diagnosis of aluminium-related bone disease in patients on regular haemodialysis. AB - Bone biopsy in an invasive method of diagnosing aluminium related bone disease (ABD). Toxic side-effects have been reported with the currently used 'high-dose Desferrioxamine (DFO) tests.' A low-dose DFO test was evaluated for the diagnosis of ABD in 28 symptomatic patients (13 male) on regular haemodialysis treatment. DFO 0.5 g diluted in 100 ml of 0.9% sodium chloride was given intravenously during the first 2 h of dialysis. Aluminium estimation before (t1) and 48 h after DFO challenge (t2) were made by DC plasma emission spectrometry. Following the DFO test bone biopsy was performed and the specimen stained for aluminium using soluchrome zurine. The DFO test was considered positive if the t2 concentration was 150 micrograms/l or treble the amount of t1. Nineteen patients (8 male) fell into this group and all except two had ABD. Of the nine remaining patients (5 male) who had a negative DFO test none had ABD. We conclude that ABD can be diagnosed safely in the majority of patients using a low-dose DFO test, thereby avoiding toxic side-effects. PMID- 1922910 TI - Stepwise correction of anaemia by subcutaneous administration of human recombinant erythropoietin in patients with chronic renal failure maintained by continuous ambulatory peritoneal dialysis. AB - Sixteen anaemic CAPD patients (Hb less than 9 g/dl) were treated with thrice weekly subcutaneous recombinant erythropoietin, epoetin-alfa. The dose was adjusted to induce a stepwise increase in haemoglobin. Fourteen patients reached a first target haemoglobin of 11.0-11.5 g/dl and eight of these a second of 13.0 13.5 g/dl, but one could not be maintained at this level. Failure to reach or maintain the second target in nine subjects was accounted for by incomplete responses associated with infection in one, extreme shortening of red-cell survival in another, and was unexplained in one subject. These three received the maximum dose studied of 450 IU/kg per week. Six other subjects were withdrawn from the study for reasons unrelated to treatment with erythropoietin. The median dose required to maintain the haemoglobin at 11.0-11.5 g/dl was 75 IU/kg per week and at 13.0-13.5 g/dl was 150 IU/kg per week. Quality of life, assessed in 12 patients at haemoglobin 11.0-11.5 g/dl, showed significant improvement in energy, and at 13.0-13.5 g/dl improvements in sleep and emotional wellbeing became significant. Twelve subjects required either institution of, or an increase in, treatment for hypertension. The thrice-weekly subcutaneous doses of erythropoietin were well tolerated and were a convenient and effective treatment for anaemia in patients on CAPD. PMID- 1922911 TI - Leukotriene release from peripheral and peritoneal leukocytes following exposure to peritoneal dialysis solutions. AB - During continuous ambulatory peritoneal dialysis (CAPD), peritoneal host defence mechanisms are repeatedly exposed to dialysis solutions (with unphysiological composition) which may compromise peritoneal immune cell functions. In this context, the current study focused on the capacity of peripheral and peritoneal PMN to release leukotrienes following exposure to conventional CAPD dialysates. PMN were obtained from peripheral blood of healthy volunteers and from the peritoneal effluent of CAPD patients with acute peritonitis. Following isolation, cells were incubated in fresh CAPD dialysates or control buffer, and calcium ionophore A23187-stimulated leukotriene synthesis was measured. Additional experiments included RP-HPLC analysis and radioactivity monitoring of lipoxygenase products in PMN labelled with 14C-arachidonic acid. Leukotriene B4 and leukotrienes C4/D4/E4 were determined by radioimmunoassay. Ionophore triggered leukotriene release from cells exposed to control buffer was pronounced in inflammatory peritoneal PMN (70.4 +/- 31.3 ng/5 x 10(6) cells LTB4 and 13.4 +/ 19.8 ng/5 x 10(6) cells LTC4/D4/E4, mean +/- SD, n = 14) when compared to healthy peripheral PMN (26.6 +/- 16.9 ng/ml LTB4 and 6.3 +/- 6.6 ng/ml LTC4/D4/E4, n = 12). Incubation in fresh solutions for peritoneal dialysis severely depressed leukotriene release from both cell populations. These results indicate a severe inhibition of cellular responsiveness as a consequence of dialysate exposure which could contribute to the impairment of host defence early in the CAPD cycle. PMID- 1922912 TI - Combined liver-kidney and isolated liver transplantations for primary hyperoxaluria type 1: the European experience. The European Study Group on Transplantation in Hyperoxaluria Type 1. AB - The data provided by 14 European centres concerning 22 combined liver-kidney and two isolated liver grafts performed in primary hyperoxaluria type 1 (PH1) were discussed at a workshop which drew the following main conclusions: 1. In end stage renal failure due to PH1 1-year kidney graft survival rate is far better after combined liver-kidney transplantation than after kidney transplantation alone. This may be due to enhanced renal graft tolerance induced by the simultaneously grafted liver, in addition to the reduced risk of oxalate-induced damage to the kidney graft because the oxalate overproduction has been corrected. 2. Prolonged dialysis using conventional regimes gives rise to extensive systemic oxalosis, especially oxalate osteopathy, which leads to long-lasting excretion of large amounts of oxalate even after oxalate synthesis has been normalised by liver-kidney transplantation, with the risk of jeopardising the success of the kidney graft. In addition, oxalate arteriopathy may endanger the recipient's life. 3. Patients whose GFR is in the range of 25-60 ml/min per 1.73 m2 should be followed up closely, with sequential assessments based on the rate of loss of overall renal function and the plasma and urine oxalate values. An isolated liver transplantation should be considered once the disease has been shown to be following an aggressive course. If this strategy is not followed, planning for an elective liver-kidney graft should begin when GFR decreases to about 25 ml/min per 1.73 m2 and the operation should be as soon as possible. 4. As orthotopic liver transplantation involves the removal of the recipient's biochemically defective but otherwise normal liver, the diagnosis of PH1 should be unequivocally established in every case by the measurement of alanine: glyoxylate aminotransferase enzyme activity in a preoperative liver biopsy. PMID- 1922913 TI - Circadian rhythm of T-lymphocyte subsets, cortisol and cyclosporin in kidney transplanted subjects. AB - The present study deals with the 24-h changes in circulating lymphocyte subpopulations in eight subjects with kidney grafts established for 2 to 5 years and treated with cyclosporin. The control group consisted of ten age-matched clinically healthy subjects. The chronobiological analysis of time series documented that the circadian rhythm of T-lymphocyte subsets is undetectable in transplanted subjects. Cortisol rhythmicity persists, however, suggesting that the abolition of T-cell rhythmicity is not attributable to a desynchronisation of the adrenal cycle. Even though the therapy was combined with prednisolone, the abrogation of rhythmicity for T-lymphocyte subpopulations seems to be related to the immunosuppressive action of cyclosporin, as the plasma concentrations of the drug show no periodic variations along the 24-h span. Antirejection therapy of kidney-transplanted subjects could be adjusted so that cyclosporin is given at a time that would promote suppression of T-lymphocytes without altering their rhythmic performance. PMID- 1922914 TI - Rapidly progressive glomerulonephritis and nephrotic syndrome associated with Mycoplasma pneumoniae pneumonia. PMID- 1922915 TI - Ischaemic hepatic necrosis and intestinal infarction in a haemodialysis patient. PMID- 1922916 TI - EDTA-ERA and WHO diagnostic codes. PMID- 1922917 TI - Omega-3 fatty acids in haemodialysis patients. PMID- 1922918 TI - Autoradiographic distribution of pituitary adenylate cyclase activating polypeptide (PACAP) binding sites in the rat brain. AB - Distribution of pituitary adenylate cyclase activating polypeptide (PACAP) binding sites was investigated in the rat brain and pituitary gland by means of in vitro autoradiography. High densities of specific [125I]PACAP binding were observed in the anterior pituitary, hippocampus (CA1-4 and dentate gyrus) and in the superior colliculus. Moderate to high labeling was observed in the periaqueductal gray matter, substantia nigra pars compacta, and in the habenula. The hypothalamus, thalamus, ventral tegmental area (VTA), mammillary body and medial geniculate body were moderately labeled. The present results support possible actions of PACAP on the pituitary functions, and further suggest that PACAP is a neurotransmitter/neuromodulator in the central nervous system. PMID- 1922919 TI - A quantitative study of the coincidence of blood vessels and A4 protein deposits in Alzheimer's disease. AB - The spatial relationship between A4 protein deposits and blood vessels in the brains of 6 elderly cases of Alzheimer's disease has been investigated. Sections were taken from medial temporal cortex and were double immunostained for A4 protein and type IV collagen, the latter being employed as a marker of blood vessels. By comparing the observed area of vessel overlying A4 deposit with that predicted from the product of A4 deposit and blood vessel area fractions it is shown that, contrary to expectations, the likelihood of a vessel co-inciding with an A4 deposit is less than would be expected by chance. It would therefore appear that the previously described positive association between A4 deposits and blood vessels reflects the abundance of A4 and the high vascularity of the cortex rather than any specific correlation between the two features. PMID- 1922920 TI - Immobilisation stress induces a paradoxical sleep rebound in rat. AB - An immobilisation stress (IS) of 2 h applied to rats at the beginning of the dark period (12 h), i.e. when the animals are more active, induces during the 10 consecutive h a significant rebound (+92%) of paradoxical sleep (PS) while slow wave sleep state (SWS) is poorly affected. Two h of sleep deprivation, also applied at the beginning of the dark period and realized either by the platform technique or by maintaining the animals awake with gentle handling, do not affect significantly subsequent SWS and PS. Finally, when repetitive IS are inflicted to the animals (one IS of 2 h every 3 days) an attenuation of the PS rebound is observed. These data suggest that a qualitative aspect of the waking state as in an intense stressful situation might be the source of a hormonal process inducing a PS excess. PMID- 1922921 TI - NMDA induces protein kinase C translocation in hippocampal slices of immature rat brain. AB - N-Methyl-D-aspartate (NMDA)-induced translocation of protein kinase C (PKC) from cytosol to membrane fractions was examined by the methods of [3H]phorbol 12,13 dibutyrate binding and western blotting in rat hippocampal slices. NMDA and L glutamate induced translocation of PKC from cytosol to membrane fractions in immature rat hippocampal slices, but not in mature ones. The NMDA-induced translocation of PKC was dependent on Ca2+. It was inhibited by the NMDA receptor antagonists, 2-amino-5-phosphonovaleric acid and ketamine, but not by Mg2+ and Zn2+. These results suggest that stimulation of NMDA receptors enhances Ca2+ influx and thereby induces translocation of PKC in immature rat hippocampus. PMID- 1922922 TI - Changes in cerebral blood flow do not directly affect in vivo recovery of extracellular lactate through microdialysis probe. AB - Influence of striatal blood flow changes on recovery of extracellular lactate in vivo through a microdialysis probe implanted into the neostriatum was investigated in halothane anesthetized rats. Relative radioactivity loss of [14C]lactate from perfusate medium through a microdialysis probe was continuously measured in vivo as an indicator of relative recovery of extracellular lactate through the probe because both the relative recovery of lactate and the relative hot loss of [14C]lactate through a microdialysis probe were similar to each other in vitro. The relative hot loss of [14C]lactate decreased in parallel with decreases in the striatal blood flow, while it did not significantly change in response to increases in the blood flow up to 200% of control. These results demonstrate that recovery of extracellular lactate in vivo through the microdialysis probe is not directly influenced by changes in the cerebral blood flow. PMID- 1922923 TI - Comparison of DNA contents of visceral organs in rats with ventromedial hypothalamic lesions and fed a high fat diet. AB - Bilateral lesions of ventromedial hypothalamus are followed by a number of changes including vagal hyperactivity and hyperinsulinemia. To investigate if cell proliferation occurs in visceral organs in rats with ventromedial hypothalamic (VMH) lesions and fed a high fat diet, we determined DNA contents of visceral organs (liver, pancreas, small and large intestines, spleen, kidney and heart) 1 and 4 week after VMH lesions or start of high fat diet. In rats with VMH lesions, DNA contents increased significantly in liver, pancreas, and small and large intestines at 1 week, and maintained the same levels until the 4th week. DNA contents increased most in the pancreas, followed by small and large intestines, and liver. DNA content did not change in spleen, kidney, or heart. In rats fed a high fat diet, there was no increase in the DNA content of these organs, except in the small intestine at 4 weeks. The results suggest that VMH lesions produce excessive DNA synthesis in visceral organs, whereas a high fat diet does not. VMH lesions may induce cell proliferation in visceral organs through vagal hyperactivity and/or changes of humoral growth factors. PMID- 1922924 TI - Acetylcholine and norepinephrine mediate slow synaptic potentials in normal and epileptic neocortex. AB - Slow excitatory postsynaptic potentials (EPSPs) were identified in rat neocortical slices. Such potentials, resistant to blockade of glutamate and gamma aminobutyric acid-A (GABAA) receptors, were partially antagonized by muscarinic or beta-adrenergic antagonists separately, and completely blocked when these agents were added in combination. Slow EPSPs were enhanced by a cholinesterase inhibitor or catecholamine reuptake blockers. Spontaneous epileptic discharges induced by picrotoxin also triggered slow EPSPs. Such potentials were pharmacologically identical to those induced by electrical stimulation under normal conditions. A non-conventional mechanism for synaptic transmission is postulated to account for triggering of slow EPSPs by epileptic discharges. PMID- 1922925 TI - Fucosylated glycoconjugates in human dorsal root ganglion cells with unmyelinated axons. AB - The same subset of small neurons in human dorsal root ganglia (DRG) was recognized by both of the two probes binding to fucosylated residue. Ulex europaeus agglutinin I (UEA-1) lectin and anti-fucosyl GM1 antibody, although these probes bind to different glycoconjugates. UEA-1 lectin also bound to unmyelinated axons in DRG and in biopsied sural nerve, but not to any neurons or unmyelinated axons in the sympathetic ganglia. Thus UEA-1 lectin and anti-fucosyl GM1 antibody may be used as specific probes for primary sensory neurons with unmyelinated axons. PMID- 1922926 TI - The immediate-early genes c-fos and c-jun are differentially expressed in the rat adrenal gland after capsaicin treatment. AB - In situ hybridization histochemistry was used to study the expression of c-fos and c-jun mRNA in the rat adrenal gland of untreated and capsaicin treated rats. In untreated animals, very low levels of c-fos mRNA were present both in zona fasciculata and reticulata of the adrenal cortex, with no detectable labelling in the zona glomerulosa or adrenal medulla. In contrast, the levels of c-jun mRNA were high in the cortical layers fasciculata and reticulata, again without labelling in the zona glomerulosa or adrenal medulla. After capsaicin (25 mg/kg, s.c.), a rapid increase in both c-fos and c-jun mRNA levels was observed in adrenal medulla. Capsaicin also induced an increase in c-fos mRNA levels in all 3 cortical layers, especially in the zona glomerulosa, whereas only small changes in c-jun mRNA levels were seen in zona fasciculata and reticulata. The present results indicate that c-fos and c-jun mRNA levels are both increased in the adrenal gland after capsaicin treatment, although the time course, magnitude and regional distribution of these increases differed for the two mRNAs. PMID- 1922927 TI - Iontophoretic application of NMDA produces different types of excitatory responses in developing human cortical and caudate neurons. AB - The effects of iontophoretically applied N-methyl-D-aspartate (NMDA) were assessed in human neocortical and caudate neurons. NMDA depolarized cell membranes, decreased input conductances and induced firing. The discharge patterns differed in the two areas studied. In neocortex, NMDA produced repetitive spikes or bursts. In caudate, it induced slow, rhythmic plateau depolarizations accompanied by an initial burst of action potentials, followed by low amplitude, long duration spikes. After hyperpolarizations were seen after each depolarization in the caudate. These variations in patterns of excitation may relate to differences in local circuits intrinsic to each region, and/or to membrane conductances specific to each type of cell. PMID- 1922928 TI - Solubilization of asymmetric acetylcholinesterase by polyanions. AB - A number of polyanions, including polysulfates (sulfated glycosaminoglycans (GAGs), dextran and pentosan sulfates, and polyvinylsulfate), polyphosphates (tetrapolyphosphate, polyadenylate) and polycarboxylates (polyaspartate, polyglutamate) solubilize asymmetric acetylcholinesterase (AChE) from chick muscle at low ionic strength, and partially or totally displace AChE tailed forms bound to heparin-agarose columns. The previously reported solubilization of asymmetric AChE by heparin, or the proven affinity of the tailed enzyme forms for this GAG, cannot therefore be taken as direct proof of the involvement of heparin like heparan sulfate proteoglycans in the anchorage of the collagenous tail of the enzyme to the basal lamina in skeletal muscle. PMID- 1922929 TI - Monoamine oxidase inhibitors prevent striatal neuronal necrosis induced by transient forebrain ischemia. AB - Seven days after 30 min of ischemia, neuronal necrosis was observed in the striatum. Pretreatment with type A monoamine oxidase (MAO-A) inhibitors, clorgyline and RS-8359 ((+)-4-(4-cyanoanilino)-7-hydroxycyclopenta (3,2-e) pyrimidine) decreased significantly the number of necrotic neurons and inhibited changes in the dopamine metabolite contents during and after transient ischemia. An MAO-B inhibitor, deprenyl also decreased the neuronal necrosis, but it inhibited only the changes in 3,4-dihydroxyphenylacetic acid (DOPAC) content after reperfusion. The results suggest that the activation of dopamine metabolism after transient ischemia was mainly mediated by MAO-A and partly by MAO-B and suggest a possible role of dopamine deamination by MAO in the development of ischemic neuronal necrosis. PMID- 1922930 TI - Mechanisms of presynaptic inhibition studied using paired-pulse facilitation. AB - An investigation was made of the effect of presynaptic inhibition on paired-pulse facilitation (PPF) of group Ia afferent excitatory postsynaptic potentials (EPSPs). The main finding from this study was that PPF was enhanced during presynaptic inhibition of compound Ia EPSPs. This increase in PPF is identical to that seen at other synapses when the probability of transmitter release is decreased by lowering the extracellular calcium or raising the extracellular magnesium concentration, providing unequivocal evidence that presynaptic inhibition is associated with a decrease in the probability of transmitter release. Further, by analogy with the effects of reduced calcium influx on PPF at other synapses, the results support the idea that presynaptic inhibition is associated with reduced calcium influx into nerve terminals. PMID- 1922931 TI - Calcium facilitation of group Ia EPSPs evoked in cat spinal motoneurones in vivo. AB - The extracellular environment of motoneurones in the cat spinal cord in vivo was altered by means of local perfusion of the central canal. Intracellular recordings were made to determine the effects of raised extracellular Ca2+ or Mg2+ concentration on the monosynaptic afferent excitatory postsynaptic potential (EPSP). Raised extracellular Mg2+ concentration reversibly reduced the EPSP amplitude, whereas raised extracellular Ca2+ concentration produced extremely large increases in the monosynaptic EPSP amplitude, up to almost an order of magnitude. In some cases, a reduction in amplitude of the EPSP and a delay in its onset were also observed, following raised extracellular Ca2+ concentration. This effect was thought to be due to a divalent cation block of the presynaptic action potential. A major conclusion from this study is that group Ia afferent terminals have a much greater transmitter release capacity than suggested by previous studies at this connection. PMID- 1922932 TI - Oxypurinol reduces focal ischemic brain injury in the rat. AB - When measured within 2 days of a unilateral occlusion of the middle cerebral artery (MCA) combined with tandem occlusion of the ipsilateral common carotid artery in rats, contralateral neurological deficits were detectable, with brain swelling and a consistent degree of neocortical infarction in the ipsilateral hemisphere. Oxypurinol (40 mg/kg i.p. administered 0.5 h prior to, and 24 h after, the onset of focal ischemia) significantly reduced the development of the ischemic infarct (P less than 0.001); attenuated tissue swelling (P less than 0.01) and ameliorated the neurological deficits (P less than 0.05). These findings suggest that this compound may be useful for the prevention or treatment of ischemic brain injuries, such as those occurring during stroke. PMID- 1922933 TI - 2-Chloroadenosine attenuates NMDA, kainate, and quisqualate toxicity. AB - Excitatory amino acid (EAA)-induced cell death in the striatum is dependent upon intact glutamatergic afferents arising from the cerebral cortex. Through a mechanism possibly related to inhibition of glutamate release, adenosine receptor agonists attenuate EAA induced toxicity in the rat striatum. In the present study, we examined whether 2-chloroadenosine (2CLA), a stable adenosine analog, protects against toxicity induced by kainate (KA), quisqualate (QUIS), N-methyl-D aspartate (NMDA), and ibotenate (IBO). In vivo intrastriatal injections of 2CLA (50 nmol) with each EAA tested provided a partial but significant protective effect versus injection of the EAA alone, as measured by striatal concentrations of gamma-aminobutyric acid (GABA) and substance P-like immunoreactivity (SP-LI). These results show that 2CLA attenuates both NMDA- and non-NMDA-mediated neuronal cell death. PMID- 1922934 TI - Does androgen affect axonal transport of cholera toxin HRP in spinal motoneurons? AB - We examined the effect of systemic androgen levels upon the rate at which lumbosacral motoneurons are labeled with cholera toxin-conjugated horseradish peroxidase (CT-HRP) injected into target muscles. CT-HRP first reaches the spinal nucleus of the bulbocavernosus between 8 and 10 h after injection into the bulbocavernosus muscle of adult male rats, but the number of motoneurons filled with CT-HRP does not differ between androgen-treated and control castrates at any of the time points examined. Thus, contrary to current speculation, we found no evidence that androgen can affect retrograde transport of CT-HRP by rat motoneurons. PMID- 1922935 TI - Simple spike modulation of Purkinje cells in the cerebellar nodulus of the pigmented rabbit to optokinetic stimulation. AB - In immobilized pigmented rabbit anesthetized with N2O (70%) and halothane (2-4%), simple and complex spike responses of Purkinje cells in the cerebellar nodulus to large field optokinetic stimulation (OKS) was studied. About half of the cells showed significant simple spike modulation to OKS delivered to ipsilateral (25/57) or contralateral (18/31) eye. The preferred direction and the amplitude of modulation of simple spike responses did not necessarily correlate with those of complex spike responses, suggesting that the simple spike modulation is not secondary to complex spike modulation but due to modulation of mossy fiber activity to OKS. PMID- 1922936 TI - Hypersensitivity of dorsal horn wide dynamic range neurons to cutaneous mechanical stimuli after transient spinal cord ischemia in the rat. AB - The responsiveness of dorsal horn wide dynamic range (WDR) neurons to cutaneous mechanical stimuli was studied in decerebrate, spinalized, unanesthetized rats before and after transient photochemically induced spinal cord ischemia. In normal rats, the discharges of dorsal horn WDR neurons to the graded mechanical stimuli applied with calibrated von Frey hairs increase linearly. One to four days after spinal ischemia, when the rats exhibit a strong allodynia-like behavioral reaction to cutaneous stimuli, the sensitivity of dorsal horn WDR neurons to mechanical pressure is greatly increased. There is a significant decrease in the threshold pressure to evoke neuronal discharges and the exponential stimulus-response curve is shifted to the left. Thus, transient ischemia of the spinal cord results in hyperexcitability of dorsal horn WDR neurons, which may underly the allodynia-like sensory abnormalities observed in behaving animals. The present results may contribute to understanding the mechanism of the development of chronic central pain in patients after central nervous system injury involving ischemia. PMID- 1922937 TI - Long-term potentiation in rat hippocampal slices is impaired following acute lead perfusion. AB - Orthodromically evoked field potentials were recorded in the CA1 region of hippocampal slices while perfusing the slices with media containing lead acetate. High-frequency stimulation (HFS) was applied to the stratum radiatum during lead perfusion. In half of the slices investigated, HFS resulted in an initial increase of the evoked responses which decayed again after about 10 min. In the other half the evoked responses increased only after the washout of lead and this potentiation was comparable to untreated controls. The lead-induced depression of the long-term potentiation might be related to the behavioral deficits observed in chronically lead-exposed mammals. PMID- 1922938 TI - The onset of pain related behaviours following partial beak amputation in the chicken. AB - The number of pecks delivered by birds to an attractive visual stimulus was measured before and again 6, 26 and 32 h after partial beak amputation. There was a significant reduction in the number of pecks by birds 26 h after amputation but not at 6 h after. This reduction was considered to be a quantitative measure of pain related guarding behaviour. The results indicated the presence of a pain free period immediately following amputation which may last in some birds for as long as 26 h. PMID- 1922939 TI - Alzheimer patients: preamyloid deposits are immunoreactive with antibodies to extracellular domains of the amyloid precursor protein. AB - In patients with Alzheimer's disease, in patients with Down's syndrome and in aged non-demented individuals, anti-beta-protein antibodies label not only the fibrillary amyloid, but also preamyloid deposits. The latter are made up of amorphous material lacking the tinctorial, optical and ultrastructural properties of amyloid fibrils. To investigate the antigenic profile of preamyloid deposits, we have carried out an immunohistochemical study on specimens of cerebral cortex from 4 Alzheimer patients and two non-demented individuals, using antibodies to the beta-protein (anti-SP28), the C-terminal region of the amyloid precursor protein (APP) (anti-SP20) and an APP extracellular epitope between residues 50 and 100 (anti-preA4). Anti-preA4 and anti-SP28 immunoreactivity was found to be present in preamyloid deposits, whereas anti-SP20 immunoreactivity was not. These findings suggest that an extracellular portion of APP, close to the N-terminus of the molecule, participates with beta-protein in the composition of preamyloid deposits. PMID- 1922940 TI - Exact cleavage site of Alzheimer amyloid precursor in neuronal PC-12 cells. AB - We have identified the secretory cleavage site in the Alzheimer amyloid precursor (APP) in a non-transfected neuronal cell line, using cyanogen bromide digests of APP purified from medium conditioned by PC-12 cells which were differentiated to a neuronal phenotype. The results obtained are most consistent with proteolysis of the Lys16-Leu17 bond in the beta amyloid peptide, followed by partial removal of Lys16 by a basic carboxypeptidase. PMID- 1922941 TI - Photoperiod effects on bombesin- and cholecystokinin-like immunoreactivity in the suprachiasmatic nuclei of the Djungarian hamster (Phodopus sungorus). AB - The immunocytochemical distribution of the putative satiety peptides bombesin (BBS) and cholecystokinin (CCK) were studied in the hypothalamic suprachiasmatic nuclei (SCN) of male and female Djungarian hamsters (Phodopus sungorus) held under either long (light/dark, LD 16:8 h) or short (LD 8:16) photoperiod. The animals were killed by perfusion with a fixative at the middle of the light period and the tissue was processed by routine immunohistochemical methods. Perikarya exhibiting BBS- or CCK-like immunoreactivity (LI) were found in the SCN of animals of all groups. Sex-related differences were not observed. In contrast, long-term exposure to short days decreased the number of neurons exhibiting CCK LI dramatically when compared to long-day animals, while BBS-LI was not affected. The results suggest that CCK in the SCN is involved in the regulation of differential food intake in this highly photoperiodic rodent species. PMID- 1922942 TI - Effect of depolarization on striatal amino acid efflux in perinatal rats: an in vivo microdialysis study. AB - We used in vivo microdialysis to determine if infusion of depolarizing concentrations of potassium stimulated striatal excitatory amino acid (EAA) efflux in post-natal day (PND) 7 rats. Dialysis probes were perfused with 100 mM KCl for 60 min (n = 6); EAA efflux was unaffected until 40-60 min after onset of the infusion, when a trend towards increased EAA efflux was observed (glutamate 284 +/- 56% of baseline). In animals exposed to 8% oxygen (n = 7) before a more prolonged (100 min) KCl infusion, again over the first 40 min of KCl there were no changes in EAA efflux; subsequently, glutamate, aspartate and taurine efflux increased (peak values 682 +/- 187%, 228 +/- 32%, and 1208 +/- 437% of baseline). These data suggest that in PND 7 rats a substantial contribution to basal striatal EAA efflux may be derived from non-neurotransmitter pools. PMID- 1922943 TI - Fluoro-Gold's toxicity makes it inferior to True Blue for long-term studies of dorsal root ganglion neurons and motoneurons. AB - We studied the long-term effects of two retrogradely transported fluorescent dyes on survival of dorsal root ganglion neurons (DRGNs) and motoneurons (MNs). In adult female rats, we labeled DRGNs and MNs by soaking the cut sciatic nerve in Fluoro-Gold or True Blue. With True Blue, we found no difference in the number of labeled MNs or DRGNs in rats surviving 4 days or 20 weeks after nerve soak. With Fluoro-Gold, labeled DRGNs and MNs were decreased at 20 weeks compared with 4 days. Since there was no offsetting increase in unlabeled DRGNs at 20 weeks, Fluoro-Gold caused cell death. PMID- 1922944 TI - Longitudinal study on age-related changes of working and reference memory in the rat. AB - Age-related changes of working memory and reference memory were examined using different age groups of Fischer 344 rats (cross-sectional study) and one group of the same strain which was repeatedly tested at different age points (longitudinal study). Delayed non-matching test in a T-maze revealed 3 points as follows: (1) since motivation by food deprivation in the task performance seemed to decrease with aging, it was needed to adjust the food deprivation level so as to attain a similar degree of motivation in different age groups; (2) scores in reference memory task remained very high in the aged in both cross-sectional and longitudinal studies; and on the other hand (3) performance of working memory task declined with aging to the same degree in both cross-sectional and longitudinal studies, suggesting that working memory progressively deteriorates in advancing age. PMID- 1922945 TI - Induction of corticospinal target finding by release of a diffusible, chemotropic factor in cervical spinal grey matter. AB - The outgrowth of corticospinal tract axons in rat spinal cord primarily occurs during the first postnatal week. Axons originating from a group of layer V pyramidal cell bodies situated in the anterior part of the cerebral sensorimotor cortex project mainly to the cervical gray matter (Joosten et al., Dev. Brain Res., 36 (1987) 121-130). By co-culturing explants of the anterior part of the sensorimotor cortex and of cervical spinal gray matter in 3-D collagen gels, a target-specific directional growth of cortical axons towards the cervical spinal gray explant could be demonstrated. After retrograde filling with the fluorescent tracer 1,1-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI), in vivo as well as in vitro, most of the DiI-labelled cortical neurons were located in layer V of the cortical explant, and were characterized by a pyramidal shape. These data suggest that the cervical spinal gray matter target area becomes innervated by corticospinal axons through the release of a diffusible chemotropic factor. PMID- 1922946 TI - Is the oligodendroglial differentiation of bipotential oligodendrocyte-type 2 astrocyte progenitors promoted by autocrine factors? AB - When immature O-2A (oligodendrocyte-type 2 astrocyte) lineage cells purified from rat mixed cortical glial cultures were subcultured at low density in 10% fetal calf serum (FCS)-containing medium they largely differentiated into type-2 astrocytes. When the same number of cells was subcultured at high density in the same volume of medium the proportion of O-2A progenitors differentiating into oligodendrocytes was substantially increased. The possibility that oligodendrocyte differentiation in high-density cultures is facilitated by autocrine factors is supported by the observation that a medium conditioned by high-density subcultures of purified O-2A cells contains high molecular weight (greater than 30 kDa), non-mitogenic factor(s) capable of inducing a rapid differentiation of immature 0-2A cells into oligodendrocytes even in low-density cultures. PMID- 1922947 TI - Nicotine-induced fos-like immunoreactivity in rat sympathetic ganglia and adrenal medulla. AB - The expression of c-fos proteins (Fos) in principal sympathetic neurons and adrenal chromaffin cells was studied immunocytochemically after a single s.c. injection of nicotine (2mg/kg). One and 2 h after injection most of the adrenal chromaffin cells showed nuclear Fos-like immunoreactivity (Fos-IR). In the superior cervical ganglion more than 80% of the neuronal nuclei were Fos-IR 2-5 h after nicotine administration, whereas only 50-60% of the neurons in the hypogastric ganglion were immunoreactive at these time points. The results suggest that nicotinic receptor mediates signal transduction, which induces c-fos expression both in sympathetic neurons and in adrenal chromaffin cells in vivo. PMID- 1922948 TI - Immunohistochemical evidence for the presence of type B monoamine oxidase in histamine-containing neurons in the posterior hypothalamus of cats. AB - Using a double immunostaining method, we demonstrated that type B monoamine oxidase (MAO-B) immunoreactivity was present in virtually all histamine (HA) immunoreactive neurons in the posterior hypothalamus of the cat. Not all MAO-B positive neurons, however, displayed HA immunoreactivity: a minor group of neurons immunoreactive for MAO-B alone was observed in the area dorsolateral to the caudal arcuate nucleus. The results suggest that the degradation of tele methylhistamine might occur within the intraneuronal structures of histaminergic neurons. PMID- 1922949 TI - Short-term dopaminergic regulation of GABA release in dopamine deafferented caudate-putamen is not directly associated with glutamic acid decarboxylase gene expression. AB - In vivo microdialysis and in situ hybridization were combined to study dopaminergic regulation of gamma-amino butyric acid (GABA) neurons in rat caudate putamen (CPu). Potassium-stimulated GABA release in CPu was elevated following a dopamine deafferentation. Local perfusion with exogenous dopamine (50 microM) for 3 h via the microdialysis probe attenuated the potassium-stimulated increase in extracellular GABA in CPu. Expression of glutamic acid decarboxylase (GAD) mRNA was also increased in the dopamine deafferented CPu. However, local perfusion with dopamine had no significant attenuating effect on the increased GAD mRNA expression. These findings indicate that dopaminergic regulation of GABA neurons in the dopamine deafferented CPu includes both a short-term effect at the level of GABA release independent of changes in GAD mRNA expression and a long-term modulation at the level of GAD gene expression. PMID- 1922950 TI - The use of locomotor activity as a behavioral screen for neuronal damage following transient forebrain ischemia in gerbils. AB - Five min bilateral carotid artery occlusion (BCO) in gerbils results in selective degeneration of neurons in the hippocampus, striatum and cortex, and an increase in spontaneous locomotor activity. These phenomena were examined to determine if an association could be made between the site or degree of neuronal degeneration and the increase in locomotor activity. The distance traveled by the BCO gerbils in a novel cage 1, 4, and 28 days after a 5 min occlusion was significantly greater than control. The extensive pyramidal cell damage in the CA1 region of the hippocampus in BCO gerbils was associated with the significant increase in locomotor activity. The increase in locomotor activity did not correlate with either the striatal or cortical damage present. The increase in gerbil locomotor activity following a 5 min BCO can be used as a predictor of CA1 damage, but not as a predictor of striatal or cortical damage. PMID- 1922951 TI - Frequency-specific position shift in the guinea pig organ of Corti. AB - The organ of hearing is tuned as expressed both in the vibratory response of the cochlear partition and in the resulting receptor potentials of the sensory cells. We now demonstrate a sharply tuned response, consisting of a position shift of the surface of the organ of Corti, occurring during the presentation of a tone. The magnitude of the position shift exceeds that of the vibratory response to the stimulus. The shift is most pronounced in the region of the outer hair cells, and its affected by an inhibitor of outer hair cell motility. We conclude that the response is induced by the action of the outer hair cells. PMID- 1922952 TI - Transient expression of neurotensin mRNA in the mitral cells of rat olfactory bulb during development. AB - The transient expression of neurotensin mRNA in the mitral cells of the rat olfactory bulb was demonstrated during the perinatal period using non-radioactive in situ hybridization in which an alkaline phosphatase labelled oligodeoxynucleotide probe was used. The relative cellular content of neurotensin mRNA signal was measured by use of a microdensitometer. Neurotensin mRNA positive cells were observed in the primordium of mitral cells on embryonic day 14 and their mRNA content increased gradually up to the day of birth. During the first postnatal week, the strength of their neurotensin mRNA signal decreased dramatically, and continued to decrease until in the adult olfactory bulb neurotensin mRNA was no longer detectable. This decrease of the neurotensin mRNA content coincided with a parallel decrease of neurotensin immunoreactivity observed in the lateral olfactory tract. PMID- 1922953 TI - Modification of serotonergic immunoreactive pattern in the dorsal horn of the rat spinal cord following dorsal root rhizotomy. AB - We investigated by immunocytochemistry the reorganisation of serotonergic endings in the dorsal horn of the rat spinal cord following thoracolumbar unilateral rhizotomy. The extent of the removal of primary afferent fibres was testified 2 weeks and 4 months after surgery by the disappearance of almost all calcitonin gene-related peptide (CGRP) immunoreactivity in the dorsal horn. Two weeks after surgery, serotonin immunoreactivity was severely reduced within the whole dorsal horn. Then, after 4 months, we observed a regrowth of serotonergic axons giving rise to an immunoreactive pattern close to that of intact animals, except in lamina IIi which was spanned by growing fibres. Thus, the removal of putative targets of serotonergic axons in the dorsal horn induces a transient loss of immunoreactivity, which illustrates the interaction between primary afferents and descending bulbo-spinal fibres. PMID- 1922954 TI - Methamphetamine-induced expression of interleukin-1 beta mRNA in the rat hypothalamus. AB - The effect of methamphetamine on the expression of interleukin-1 beta (IL-1 beta) mRNA in the rat brain was investigated with Northern blot analysis. Methamphetamine (2-15 mg/kg, i.p.) caused a marked induction of IL-1 beta mRNA in the hypothalamus among the 8 brain regions examined, in a dose-dependent manner. The level of IL-1 beta mRNA reached a maximum at 1 h and rapidly declined within 2 h after the injection of 15 mg/kg. These results provide the first evidence that methamphetamine induces the expression of IL-1 beta mRNA in the hypothalamus, which may be partly involved in the production of central actions of this drug. PMID- 1922955 TI - A novel action of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin, a cofactor for hydroxylases of phenylalanine, tyrosine and tryptophan: enhancement of acetylcholine release in vivo in the rat hippocampus. AB - Recently, we have reported that 6R-L-erythro-tetrahydrobiopterin (6R-BH4), a natural cofactor for hydroxylases of phenylalanine, tyrosine and tryptophan, has a dopamine releasing action in the rat striatum independent of its cofactor role. Here we studied the effects of 6R-BH4 on acetylcholine (ACh) release in the rat hippocampus using brain microdialysis. Intracerebroventricular injection of 6R BH4 dose-dependently increased extracellular ACh levels monitored by brain microdialysis. Biopterin, an oxidized form of 6R-BH4, and 6S-BH4, an unnatural diastereoisomer of 6R-BH4, had little effect on the ACh levels. The 6R-BH4 induced increase in ACh levels was eliminated after inhibition of voltage dependent Na+ channels by tetrodotoxin, but not after depletion of catecholamines by reserpine. These results show that 6R-BH4 has direct ACh releasing action in vivo. PMID- 1922956 TI - Tumor necrosis factor-beta specifically inhibits the activity of preoptic warm sensitive neurons in tissue slices. AB - Effects of human tumor necrosis factor-beta (TNF-beta) were studied on the single neural activities of the preoptic thermosensitive and thermally insensitive neurons in tissue slices of rats. Physiological doses (0.7-40 ng/ml) of TNF-beta decreased the firing rate in most of the warm-sensitive neurons, but showed no marked tendency in the response patterns of thermally insensitive neurons. The actions of TNF-beta on warm-sensitive neurons were blocked by concurrent application of sodium salicylate. The results suggest that the intracranial TNF may produce fever through local production of prostaglandins. PMID- 1922957 TI - Abnormal brain spectrin immunoreactivity in sprouting neurons in Alzheimer disease. AB - Brain spectrin is a major membrane skeleton protein that participates in cellular transport, cell morphogenesis, neurotransmitter release and growth cone adhesion. The present study showed that in Alzheimer disease (AD) neuropil, brain spectrin immunoreactivity is co-localized with synaptophysin in the presynaptic boutons. At the ultrastructural level, brain spectrin immunoreactivity was observed in the presynaptic terminals and in the axoplasm of some myelinated and unmyelinated fibers. In addition to this normal localization of brain spectrin in the AD brain, we also found brain spectrin immunoreactivity associated with abnormal patchy lesions in the AD neuropil. Confocal laser imaging and immunoelectron microscopy revealed that these lesions corresponded to thick cellular processes derived from neurons. The findings that these structures were anti-neurofilament positive but anti-glial fibrillary acidic protein (GFAP) and Ricinus communis agglutinin I (RCA-I) negative confirm their neuronal origin, and rule out the possibility of glial origin. These structures could represent either atypical axonal or dendritic processes derived from sprouting neurons or the accumulation of brain spectrin degradation products in degenerating neurons. PMID- 1922958 TI - Long-term increase in the levels of c-jun mRNA and jun protein-like immunoreactivity in motor and sensory neurons following axon damage. AB - The immediate early genes c-fos, c-jun and NGFI-A are rapidly and transiently expressed in neurons of the superficial dorsal horn following noxious sensory stimulation. However, using either in situ hybridisation to map mRNA or specific antibodies to detect the protein products we were unable to detect any change in expression of those genes in stimulated dorsal root ganglion cells or motor neurons. In contrast levels of c-jun mRNA and protein-like immunoreactivity (but not c-fos or NGFI-A) are massively increased within dorsal root ganglion cells and motor neurons following sciatic nerve section or crush. However, these changes are neither rapid nor transient. Increased gene product is seen at 24 h but not 2 h after nerve damage and these levels are maintained up to seven days later. These results suggest that there are multiple routes for the control of c jun gene expression within the nervous system and that c-jun may play a key role in the neuronal response to injury. PMID- 1922959 TI - The axonal origin of a subpopulation of dystrophic neurites in Alzheimer's disease. AB - Dystrophic neurites are observed characteristically in Alzheimer's disease (AD). They are thought to arise from sprouting dendrites and contribute to dementia because of their abnormal growth and close association with neurofibrillary tangles and neuritic plaques. In the present study, dystrophic neurites are demonstrated in the thalamic reticular nucleus in AD in the context of a normal neural and glial architecture. They do not collocalize with somata and dendrites identified by simultaneous labeling with the microtubule-associated protein MAP2, suggesting that they are derived from axons. Throughout the brain, dystrophic neurites may well be comprised of a heterogeneous population of both dendrites and axon terminals and preterminals. While many recent studies have focused upon the dendritic origin of dystrophic neurites, these results emphasize that the interconnectivity of certain brain regions may be compromised by cytoskeletal changes occurring in neurons and their axons in AD. PMID- 1922960 TI - beta-Amyloid protein load is relatively uniform throughout neocortex and hippocampus in elderly Alzheimer's disease patients. AB - beta-Amyloid protein immunoreactivity in neocortex and hippocampus of Alzheimer's disease and control brains has been measured using an automatic image analysis system. Successive fields from the pial surface to white matter in 4 neocortical sites, parahippocampal gyrus and along the pyramidal cell layer in the hippocampus have been measured using a number of variables including: area fraction or load, counts per unit area and deposit size. In Alzheimer's disease beta-amyloid protein load in neocortex and hippocampus was significantly greater than in non-demented age-matched controls. beta-Amyloid protein load, as measured by size variables, was relatively uniform throughout the neocortex in elderly Alzheimer's disease patients. However, greater variability in deposition was measured in parahippocampal gyrus and hippocampus than in neocortex. Size and density variables used to measure beta-amyloid protein deposition were not correlated with age although there was a tendency for the cortical load to decrease with age beyond 80 years. PMID- 1922961 TI - Relationship between non-fibrillary amyloid precursors and cell processes in the cortical neuropil of Alzheimer patients. AB - We examined the ultrastructural localization of amyloid beta-protein in 8 Alzheimer neocortical biopsies. Intense immunoreactivity was located extracellularly on amyloid fibrils and amorphous material. Amorphous labelled material was also found in cell processes. No ultrastructural cell marker, such as glial fibrils, glycogen, tubules, paired helical filaments (PFHs) or synaptic vesicles could be seen in these processes that could allow their identification as glial processes, neurites or presynaptic terminals, respectively; occasional membrane stacks were observed. These findings suggest that preamyloid deposits are related to cell processes and, by elimination, that postsynaptic terminals may be involved in abnormal metabolism of the amyloid fibril precursors. PMID- 1922962 TI - Correlation between cerebrospinal fluid phenylalanine and beta-endorphin in patients with phenylketonuria. AB - Previous animal and human studies have suggested an analgesic effect of phenylalanine involving endogenous opioid peptides. Phenylalanine was measured by a HPLC method with electrochemical detection and beta-endorphin by a specific radioimmunoassay in 14 lumbar cerebrospinal fluid samples from 13 patients with phenylketonuria. Cerebrospinal fluid beta-endorphin was also determined in 6 age matched control subjects. We found a trend towards a higher beta-endorphin level in phenylketonuria (median 26.0 pM, range 13.0-37.8) than in the control subjects (20.6 pM, 12.7-28.0), P = 0.13. Cerebrospinal fluid concentrations of phenylalanine and beta-endorphin were significantly correlated (r = 0.68, P = 0.008). The results support the hypothesis that phenylalanine modifies the central endogenous opioid system. PMID- 1922963 TI - Screening for the beta-amyloid precursor protein mutation (APP717: Val----Ile) in extended pedigrees with early onset Alzheimer's disease. AB - Screening for the APP717 mutation in 5 further families with early onset Alzheimer's disease failed to reveal further cases with this variant. Screening a further 100 normal individuals for this mutation also failed to reveal further occurrences of this variant in the general population. Sequencing of exons 16 and 17 of the beta-amyloid precursor protein gene (the exons which encode the beta amyloid fragment) in pedigree FAD4 revealed them to be of normal sequence. The significance of these observations to the genetics of Alzheimer's disease is discussed. PMID- 1922964 TI - An in vitro method assaying recognition ability of nerve terminals for special substances. AB - The present study provides a simple in vitro method for detecting the ability of nerve terminals to recognize special molecules. Test molecules were applied to a restricted narrow region on the surface of culture dishes, and dissociated sympathetic neurons which were embedded in a collagen gel were placed on the surface next to the region. Sympathetic fibers distributed densely on the laminin applied region, whereas they were missing on the heparin- or hyaluronic acid applied regions. The neurites showed no response to the fibronectin- or heparan sulfate-applied region. These results indicate that sympathetic fibers have an affinity for laminin, whereas they recognize a repellent property of heparin or hyaluronic acid. PMID- 1922965 TI - N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces cytoskeletal alterations on 'Swiss 3T3' mouse fibroblasts. AB - The effect of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) on Swiss 3T3 cells was investigated. Cell morphology alterations were observed when 3T3 cell cultures were exposed for 6 h to 1.5 mM MPTP. Using indirect immunofluorescence technique, cytoskeletal elements' organization of microfilaments and microtubules, has been analysed. MPTP modified both actin and tubulin networks, stress fibers appeared less sharp and microtubules were disorganized. The effect of MPTP was completely reversible and cell viability was unaffected. These results suggest that changes in cytoskeletal organization may be the first visible effect related to biochemical alterations induced by MPTP. PMID- 1922966 TI - Age-related changes in locomotor behavior induced by MPTP in rats. AB - Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on gait was studied in young (4 weeks) and old (21 months) male rats. No significant alteration in stride length (SL) or stride width (SW) was observed 30 min after single dose MPTP treatment (3 mg/kg, i.p.) in both young and old rats. Multidose treatment with MPTP (3 mg/kg, i.p. daily for 8 days) resulted in a marked decrease in SL in old rats compared to that of old control group, while an increase in SL was found in both MPTP-treated and control young rats. In contrast, multidose MPTP administration caused no changes in SW in either young or old rats. The present result of behavioral analysis suggests that multidose MPTP neurotoxic effect on locomotor activity may be age dependent in rats and that the old rat is an appropriate model for MPTP studies. PMID- 1922967 TI - Antagonism of the effects of calcitonin gene-related peptide and of capsaicin on the guinea-pig isolated ileum by human alpha-calcitonin gene-related peptide(8 37). AB - The possible mediating role of calcitonin gene-related peptide (CGRP) in the effects of capsaicin in the guinea-pig ileum has been investigated by means of the CGRP antagonist hCGRP(8-37). Submaximal longitudinal muscle relaxation of the histamine-precontracted ileum evoked by rat CGRP (3 nM) or capsaicin (1 microM) was reversed by hCGRP(8-37) (1.5 microM), while that due to adrenaline or neurotensin was not affected. Inhibition of spontaneous circular muscle movements by capsaicin (100 nM) was also reversed by hCGRP(8-37). The CGRP antagonist had no effect on electrical stimulation-evoked ileal contractions or on the longitudinal or circular muscle tone. It is concluded that (a) hCGRP(8-37) is a specific CGRP antagonist in the ileum, apparently devoid of intrinsic activity or any effect not related to CGRP; (b) the inhibitory actions of capsaicin on the longitudinal and circular muscles of the ileum are mediated, at least in part, by CGRP. PMID- 1922968 TI - Clustering of cell bodies, bundling of dendrites, and gap junctions: morphological substrate for electrical coupling in the prepacemaker nucleus. AB - The possible morphological basis for electrical coupling between neurons of the prepacemaker nucleus was studied in weakly electric gymnotiform fish at the ultrastructural level. Three structural characteristics were found: Extremely dense clustering of cell bodies; 'bundling' of dendrites; and gap junctions between neurons. Electrical coupling may take place through gap junctions and the spatial arrangement of elements in the prepacemaker nucleus, which could enable ephaptic interactions. Such mechanisms may also be used for averaging the responses of individual neurons in the whole assembly in order to render more predictable behavioral reactions. PMID- 1922969 TI - Synaptic bodies and vesicles in the calix type synapse of chicken semicircular canal ampullae. AB - Calix afferent fibers generate depolarizing DC (direct current) and superimposed AC (alternating current) potentials in response to a vibrating stimulation of the hair bundle in an isolated preparation of a chicken semicircular canal ampulla. The wave form of the postsynaptic potential appears similar to the transduction potential of hair cells, which suggests electrical transmission in the calix type synapse. However, synaptic bodies and vesicles were found by EM observation instead of gap junctions in the hair cell presynaptic to the calix afferent. The number of synaptic body was 11-12/hair cell. These structures support chemical transmission in the calix type synapse. PMID- 1922970 TI - Caffeine-induced epileptic discharges in CA3 neurons of hippocampal slices of the guinea pig. AB - In order to analyze the elementary mechanisms underlying caffeine-induced epileptiform discharges, hippocampal slices of guinea pigs were exposed to this drug. When the bath concentration of caffeine exceeded 0.2 mM, periodically occurring paroxysmal depolarizations (PD) in CA3 neurons appeared. They were accompanied by declines of extracellular free calcium concentration and were suppressed by the organic calcium antagonists verapamil and flunarizine. PD-like fluctuations of the membrane potential could be evoked also in CA3 neurons functionally isolated by tetrodotoxin (TTX). The observations indicate that caffeine-induced PD are generated endogenously and that transmembranous calcium currents contribute to these mechanisms. PMID- 1922971 TI - The tight-junction-specific protein ZO-1 is a component of the human and rat blood-brain barriers. AB - Continuous tight junctions between vascular endothelial cells, the principal anatomical basis for the blood-brain barrier, have been investigated functionally and morphologically but their molecular components have not been defined. This communication reports that the protein ZO-1, a specific constituent of epithelial tight junctions, is found in human and rat brain vasculature. ZO-1-positive immunocytochemical staining forms a tightly banded pattern outlining individual endothelial cells in blood vessels of the human cerebral cortex. Rat brain exhibits a similar staining of blood vessels as well as ZO-1-positive staining around individual epithelial cells of the choroid plexus. The antiserum used for immunocytochemistry recognizes a protein of about 200 kDa in rat brain microvessels by Western blot. These findings indicate that ZO-1 is located at the interendothelial junctions of brain vasculature, implicating its importance as a component of the blood-brain barrier. PMID- 1922972 TI - Guided outgrowth of leech neurons in culture. AB - Sensory neurons of Hirudo medicinalis were cultivated on patterns of extracellular matrix (ECM) protein which were prepared by UV irradiation using copper grid masks. The relation of the patterns and of the outgrowth of neurites was observed by scanning electronmicroscopy after gold decoration. The neurites were guided by narrow (10 microM) lanes of ECM protein. Branching of neurites was induced by branched lanes. Bent neurites were pulled off bent lanes at some distance behind the growth cone such that their length was reduced. Regularly spaced sites of adhesion became visible which remained connected to the neurites by extended filaments. PMID- 1922973 TI - An in vitro model to study diabetic neuropathy. AB - Adult dorsal root ganglion (DRG) neurons from diabetic and normal C57BL mice were cultured and compared for survival and neurite extension. Neurons from diabetic mice have improved their survival and neurite extension when the insulin concentration was increased but it was never as good as that of controls. The increase of glucose concentration in serum-free media to ten times higher than normal improved both survival and neurite extension of neurons from diabetic animals. PMID- 1922974 TI - Victor or victim. PMID- 1922975 TI - Values and the health professions. PMID- 1922976 TI - Pleased and disturbed. PMID- 1922977 TI - Clinical textbooks: an academic hazard? PMID- 1922978 TI - Nurse case management. The coming together of theory and practice. AB - Newman proves that theory can be a practical approach to nursing care delivery by applying a theory to the new nursing role of the case manager. The illustration applies Newman's theory of health and nursing and looks at its implications for various aspects of provider interface. PMID- 1922979 TI - One method for comparing different nursing models. AB - To have diverse nursing models is well and good, but how does one select among them or even understand their differences? Sohn devises a simple method for comparing nursing models that will be of use to teachers, students, and practitioners alike. PMID- 1922980 TI - Humanistic nursing. It can't stand up to scrutiny. AB - McKinnon relates the story of a former patient to explain her disillusionment with humanistic nursing. For her, it doesn't work. PMID- 1922981 TI - Making nursing diagnosis work for you and your client. A step-by-step approach. AB - Can nursing diagnosis be brought out of the theory into practical application? Weber says yes and tells you how. Concrete examples enhance this article, as does a discussion of the many different taxonomies of nursing diagnosis. PMID- 1922982 TI - Confidentiality vs. duty to warn. Whose life is it anyway? AB - Donovan looks at some of the very real issues arising in care of the AIDS patient through this fictional legal case. Issues of confidentiality and duty to warn are contrasted. Is it possible to meet all desirable goals in these cases? Or do legal and ethical considerations conflict? PMID- 1922983 TI - Medicare expense factors. PMID- 1922984 TI - Treating renal disease: a history. AB - As dialysis technology advanced, physicians trained in the new specialty of nephrology set up dialysis programs in hospitals throughout New Jersey. Physicians, state legislators, organizations, and patients contributed to the growth of a life-saving technology. PMID- 1922985 TI - Dialysis pioneers of New Jersey. AB - Dialysis was an experimental procedure when New Jersey's earliest dialysis programs were started by physicians three decades ago. New Jersey's dialysis pioneers recall their early days in a new subspecialty. Patients were fortunate to have such programs available. PMID- 1922986 TI - Tissue plasminogen activator: hospital experience. AB - Tissue plasminogen activator (t-PA) is administered safely and efficiently in the treatment of acute myocardial infarction (MI). A study of 74 patients administered t-PA for acute MI associated with a low complication rate showed an acceptable patency rate, and a good outcome. PMID- 1922987 TI - Advances in neurology at Turner's Lane Military Hospital. AB - The work of physicians at Turner's Lane Military Hospital, Philadelphia, stimulated interest in neurology in the United States, leading to the post-Civil War emergence of neurology as a distinct medical specialty. These physicians advanced their profession and benefitted their patients. PMID- 1922988 TI - Mediastinal mass following esophageal surgery. AB - In this Radiology Rounds, the authors report the computed tomographic findings of a patient with an infected esophageal mucocele that formed within one month after repair of a perforated paraesophageal hiatus hernia. The patient was a 78-year old male. PMID- 1922989 TI - 1991 policy research perspectives. American Medical Association. AB - Three new policy perspectives--the Medicare physician payment schedule; economic status of the elderly; and new technology and Medicare expenditures--are discussed, according to current directives of the American Medical Association. PMID- 1922990 TI - Time out! Let's play charades. PMID- 1922991 TI - Consortium model for master's education in nursing. AB - The authors describe a consortium model for graduate education in nursing among four regional universities in southern Louisiana. A multi-site collaborative approach was implemented to increase educational opportunities for place-bound professional nurses while increasing institutional cooperation and achieving educational efficiencies. The development, design, and operational components of the consortium are described, and recommendations are presented for nursing administrators and faculty who may consider using a similar approach. PMID- 1922992 TI - How students perceive faculty caring: a phenomenological study. AB - Caring must be visible in the learning environment. To nurture nursing students' capacity to care, the author studied student perceptions of caring nursing student-faculty experiences. Faculty members are encouraged to provide an environment and means for nursing students to gain the skills necessary to professionalize human caring. PMID- 1922993 TI - Nursing faculty practice in the Houston Linkage Model: administrative and faculty perspectives. AB - The authors describe a model for the development and implementation of faculty practice, focusing on administrative and faculty parameters of concern in its establishment. Administrative parameters include mission and purpose, benefits to nursing education and nursing service, contractual arrangements, legal issues, use of revenues, and evaluation. The case example illustrates faculty concerns and mentorship, maintenance of clinical skills, patient care, facilitation of research for promotion/tenure, and benefits. PMID- 1922995 TI - Who is entitled to authorship? PMID- 1922994 TI - Understanding cultural diversity through a student exchange program. AB - Nursing curriculum must include multicultural experiences to prepare nurses to work with the nation's ethnically diverse population. To meet this need, a pilot project was instituted between two Bachelor's of Science in Nursing (BSN) programs. It was hypothesized that students could develop new cultural perspectives by experiencing nursing with different ethnic groups. Two senior students from each institution were selected for the experience. The exchange program provided them with opportunities to assess and care for health problems in aggregates and families with whom they might not have had practice. The authors recommend that these types of programs be encouraged to introduce students to practice in settings and with cultures other than their own. PMID- 1922996 TI - One student's perspective. PMID- 1922997 TI - Evaluation of an integrated curriculum: The Waltz Model. PMID- 1922998 TI - Stressful and satisfying experiences of adult RN/BSN learners. PMID- 1922999 TI - Teaching acceptance in nursing. PMID- 1923000 TI - Use of a checklist to teach advanced technical skills. PMID- 1923001 TI - Nursing students: minority recruitment and retention. PMID- 1923002 TI - Sampling: an experiential learning activity. PMID- 1923003 TI - Entrepreneurial nursing: the right course at the right time. AB - As more nurses start businesses of their own, there is a need for a course to help them learn to plan, organize, finance, and operate these businesses. The author describes the course's organization, its outcomes, and reactions of the first students to participate in the course. PMID- 1923004 TI - Assessing interaction patterns of students. AB - Teaching nursing students how to interact therapeutically with patients is a concern of all nursing faculty members. The verbatim process recording is one available method of analyzing student interactions. An analysis of 86 reported interactions of student nurses with postpartal maternity patients identified patterns of interaction that were related to patient concerns and showed deficits in student communication skills. PMID- 1923005 TI - Access to care threatened by DEA proposal. PMID- 1923006 TI - Sexual-addiction diagnosis supports anti-sex movement. PMID- 1923007 TI - Ventricular arrhythmia: management guidelines for the primary health care setting. AB - Ventricular arrhythmia is a common problem in the ambulatory setting. Ventricular arrhythmias that appear to be similar on the electrocardiograph may have different prognostic significance, depending on the patient's age and the presence of underlying heart disease or ventricular dysfunction. The ultimate goal in the care of any patient with ventricular arrhythmia is prevention of sudden cardiac death. Patients can usually be classified into one of five diagnostic categories, based on symptoms and evidence of underlying heart disease. This article discusses the classification of ventricular arrhythmias as either benign, potentially malignant or malignant. The risks of antiarrhythmic therapy and specific management plans for each of the five diagnostic categories are provided. These management plans are meant to serve as a framework for the clinician who provides primary care to these patients. An explanation of terms used commonly in the interpretation of ventricular arrhythmias is included, as well as guidelines for the assessment of patients with ventricular arrhythmias. PMID- 1923008 TI - Inflammatory bowel disease: primary health care management of ulcerative colitis and Crohn's disease. AB - Inflammatory bowel disease encompasses both ulcerative colitis and Crohn's disease, two conditions so alike clinically that they are frequently indistinguishable from one another. Inflammatory bowel disease occurs at a rate of approximately five per 100,000 people. It tends to cluster in families and is seen four to five times more often in Jewish Caucasians than in other Caucasians. The etiology is unknown. Increasing attention is being paid to autoimmune factors, genetic factors and food allergies, and the notion that inflammatory bowel disease has its roots in a psychological disorder continues to pale for want of empirically sound evidence. Disease pattern is one of remission and exacerbation. The aim of therapy is to maintain an optimal lifestyle in remission through an individually tailored protocol of medications. Sulfasalazine remains the medication of choice; corticosteroids have short-term utility in exacerbation; and immunosuppressants, though controversial, are thought to have some steroid-sparing benefits during acute flare-ups. Indications for surgery vary, depending on whether or not a clear differential diagnosis has been made between ulcerative colitis and Crohn's disease. There is no cure for inflammatory bowel disease except for total colectomy in clearly diagnosed ulcerative colitis. Current research endeavors seek a cause or causes for inflammatory bowel disease, but the literature does not solidly support any one possibility above other rival etiologies. PMID- 1923009 TI - Implications of the National Practitioner Data Bank for nurse practitioners. AB - The National Practitioner Data Bank is a new federal repository of data on malpractice payments and adverse actions taken against the clinical privileges and licenses of all health care practitioners. This article summarizes the law governing the data bank and its implications for nurse practitioners. Specific reporting requirements are discussed, as well as guidelines for those who must and those who can access the data bank. This article also explains how NPs are notified when reports are made and gives methods for correcting errors in reports. PMID- 1923010 TI - Setting up a school-based sexual education program to help prevent AIDS and other sexually transmitted diseases. AB - AIDS and sexually transmitted diseases (STDs) are common today, but many parents, teachers and students do not fully understand the diseases or what constitutes their prevention. Young persons, for a variety of reasons (e.g., developmental issues, peer pressure, societal influences) are becoming sexually active at earlier ages than ever before. However, early sexual activity often is not accompanied by knowledge about the consequences. Three nurse practitioners and one nurse educator from a university in the Northeast developed creative ways of educating students to help them avoid becoming the AIDS and STD patients of tomorrow. The nurses' efforts led to the development of an education program for parents and students (grades 7 through 12). The information obtained from these programs can help serve as a model for clinicians interested in conducting AIDS and STD secondary-school education programs. PMID- 1923011 TI - Managing the patient with A.R.D.S. PMID- 1923012 TI - Self-test. Managing the patient with cirrhosis. PMID- 1923014 TI - Becoming politically active. PMID- 1923013 TI - Stains of tragedy and joy. PMID- 1923015 TI - Whither nursing? PMID- 1923016 TI - RN-MSN. A shorter route to higher education. PMID- 1923017 TI - Making a good first impression. PMID- 1923018 TI - A caregiver's guide to self-care. PMID- 1923019 TI - Pain beneath the humor. PMID- 1923021 TI - Myths & facts ... about pediatric postoperative care. PMID- 1923020 TI - How to use a urinometer. PMID- 1923022 TI - Recognizing compartment syndrome. PMID- 1923023 TI - Managing pain with long-acting morphine. PMID- 1923024 TI - Judy's nurse. PMID- 1923025 TI - Everyone was pulling for Edna. PMID- 1923026 TI - Timely tips on adhesive tape. PMID- 1923027 TI - Tunnel vision. PMID- 1923028 TI - Rescue by phone. PMID- 1923029 TI - Using a Groshong central venous catheter. PMID- 1923030 TI - Dealing with older patients and their families. PMID- 1923031 TI - Ileostomy care. Overcoming the obstacles. PMID- 1923032 TI - No grounds for dismissal. PMID- 1923033 TI - A.I.D.S. patient. Understanding denial. PMID- 1923034 TI - Dealing with criticism during an evaluation. PMID- 1923035 TI - Dr. Bingham couldn't care less what nurses thought. PMID- 1923036 TI - Mandatory H.I.V. testing. Nurses and doctors say no. PMID- 1923037 TI - Making failure a positive experience. PMID- 1923038 TI - Ready to die on schedule. PMID- 1923039 TI - AIDS update. PMID- 1923040 TI - Myths & facts ... about joint commission standards. PMID- 1923041 TI - Responding quickly to asystole. How to reverse cardiac standstill and prevent brain death. PMID- 1923042 TI - Multisystem organ failure. What you need to know. PMID- 1923043 TI - Another view on opioid analgesics. PMID- 1923044 TI - Removing ticks the right way. PMID- 1923045 TI - Thank you, nurses. PMID- 1923046 TI - Patient age. Does it affect your pain-control decisions? PMID- 1923047 TI - Death investigations. How you can help. PMID- 1923048 TI - Sean kept hoping against hope. PMID- 1923049 TI - Preparing your patient for a cardiac P.E.T. scan. PMID- 1923050 TI - Self-test. Managing patients with congestive heart failure. PMID- 1923051 TI - A son's tribute. PMID- 1923052 TI - Managing patients with stress ulcers. PMID- 1923053 TI - Double-checking pump. PMID- 1923054 TI - Teaching a patient to use a cane correctly. PMID- 1923055 TI - Setting goals for success. PMID- 1923057 TI - Communication breakdown. PMID- 1923056 TI - Handling phone calls effectively. PMID- 1923058 TI - Coming to terms with breast loss. PMID- 1923059 TI - Complicated grief. PMID- 1923060 TI - Learning to let go. PMID- 1923061 TI - Postgraduate diploma: a student's view. PMID- 1923062 TI - A child's eye view. PMID- 1923064 TI - Helping patients face up to loss. PMID- 1923063 TI - Make do and mend. PMID- 1923065 TI - Light at the end of the Chunnel. PMID- 1923066 TI - Female HIV alert. PMID- 1923067 TI - Passing the buck. PMID- 1923068 TI - The truth about terminal cancer. PMID- 1923069 TI - Beef and bovine spongiform encephalopathy: the risk persists. AB - Bovine spongiform encephalopathy (BSE) is one of the transmissible spongiform encephalopathies (TSE) that are currently known to the authors to affect only mammals, including man. The diseases are progressive, fatal paralyses and dementias, for which there are no methods of certain diagnosis and no treatment. In this review the disease in cattle, the mode of transfer of these TSEs between animals by mouth, the possible presence of infective agents in the food that we eat, the resistance of BSE to cooking, and the likelihood that humans may become infected are discussed. The origins of BSE, whether from sheep, from cows, or as a mutation are considered. Whatever the origin of BSE, a substantial danger for man exists. Creutzfeld-Jakob disease (CJD), a TSE of man, may have been derived from eating infected animal tissue in the past. The possibility that this was of bovine origin and the implications that this would have for BSE infected meat in human food are discussed. PMID- 1923070 TI - The state of nutrition in Fars, Iran: a review. AB - Nutritional problems in Fars province, Iran were reviewed. The commonest problems are protein-energy malnutrition, growth retardation, zinc and iron deficiencies. Several factors have contributed to malnutrition in this province such as food habits, low intake of some nutrients, high rate of illiteracy and unsound infant feeding practices. Preventive programmes to control the nutritional disorders should be given a high priority in any health plan. Investigations on causative factors leading to malnutrition are highly recommended. PMID- 1923071 TI - What is life? AB - All that science can do is to look into processes which, apparently first began to operate four billion years ago before any scientists were present to observe or comment. These processes fall into three categories--energetics, chemistry and life. Energetics and chemistry have been documented but what about life. PMID- 1923072 TI - Nabali olive oil ripening and oil properties. AB - The effect of ripening of "Nabali" olives on the yield and some properties of the extracted oil was examined. Seven samples were harvested every 2 weeks and analyzed for moisture and oil content. The extracted oil was subjected to chemical analysis. Oil content increased and there were some significant changes in the proportions of fatty acids. Nabali olive oil is relatively high in arachidic, stearic and linoleic acids. PMID- 1923073 TI - Give us proof! PMID- 1923074 TI - Blood lipid levels in New Zealand. AB - OBJECTIVES: the study aimed to determine age and gender specific levels of lipids and lipoproteins in New Zealanders. Participants were randomly selected from 20 general electoral roles, and from a sample of 15-18 year olds. METHODS: plasma cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels were measured in 2941 men and women aged 15-99 years. RESULTS: mean (SD) plasma cholesterol was 6.0 (1.3) mmol/L in men and 6.1 (1.3) mmol/L in women. There was a marked variation in total cholesterol and calculated LDL cholesterol with age, and the pattern was different in men and women. There was also a considerable regional variation; levels tending to increase from north to south. Overall mean cholesterol levels adjusted for age and geographical distribution were 5.8 and 6.0 mmol/L for men and women respectively. CONCLUSION: the fact that approximately a third of the adult population in New Zealand under 65 years have cholesterol levels greater than 6.5 mmol/L indicates the need for effective diet and lifestyle changes to reduce the high rates of CHD. PMID- 1923075 TI - Severe acute laryngotracheitis in Christchurch 1980-90. AB - A review of children admitted to Christchurch Hospital with acute laryngotracheitis over a 10 year and nine month period revealed that 894 admissions occurred for this condition. Forty-four (4.9%) were admitted to the intensive care unit of the hospital, of whom 12 (1.3% of all laryngotracheitis admissions) required endotracheal intubation. The mean time of intubation was 170 hours (range 24-432). There were no deaths, although seven children who were intubated had serious complications, of which perforation of a gastric ulcer was the most important. In our group of patients intubation is a rare event, and the need for aggressive treatment with dexamethasone at the time of admission to the general ward is questioned. PMID- 1923076 TI - Clinical consequences and assessment of low selenium status. PMID- 1923077 TI - The change in prevalence of wheeze in seven year old children over 19 years. AB - OBJECT: to determine the change in prevalence of wheeze on clinical examination and history over a 19 year period. METHODS: a survey of random samples of seven year old children at primary schools in an urban area (Hutt Valley). Outcome measures were answers to a questionnaire and auscultation of children's chest for wheeze. RESULTS: in 1971, 1981, and 1990, the point prevalence of clinical wheeze by auscultation remained steady between 3.2% and 5.9%. However there was a significant increase in the prevalence of reported wheeze from 23% to 36% (p less than 0.001). Between 1981 and 1990 there was a 10.7% increase in the number of children who had been to their general practitioner for wheeze (p less than 0.001), a 5.3% increase in children who were on daily medication (p less than 0.001) and a 8.2% increase in the family history of asthma (p less than 0.001). There was no significant increase in the number of children who had been to hospital for wheezing. The proportion of children who were found to be wheezing on the day and whose parents did not identify a problem in their child had not changed between 1981 and 1990. CONCLUSION: there was an increasing high level of wheeze reported in the Hutt Valley with a corresponding steady level of clinical wheeze. More educational efforts are needed by primary health care workers to improve on parental perception of wheeze because a steady third of those children who were found to be clinically wheezing were recognised by their parents to have a problem. PMID- 1923078 TI - Antibiotic treatment of otitis media with effusion. AB - There are various forms of medical treatment for otitis media with effusion (OME) in children. One of these is a four week course of an antibiotic. A trial was carried out comparing cotrimoxazole with amoxicillin-potassium clavulanate in 102 cases with 181 affected ears. In addition this trial used various procedures to increase and monitor compliance, and the results showed that the compliant cases did much better than the noncompliant cases and cotrimoxazole was more effective than amoxicillin-potassium clavulanate. When the ethnic groupings were analysed the compliance was lower for the Maori (24%) and Pacific Islander (29%) than the European (49%). The success rate for the compliant cases whose middle ear effusion resolved in one or both ears had a similar result with Maori (40%), Pacific Islander (60%) and European (71%) probably indicating an increased nonmeasured compliance in the latter. PMID- 1923079 TI - An audit of surgical waiting lists. PMID- 1923080 TI - Health reform. PMID- 1923081 TI - Indiscriminate prescribing of NSAIDs. PMID- 1923082 TI - Prevalence of diabetes mellitus and impaired glucose tolerance in a New Zealand multiracial workforce. AB - A cross sectional survey was carried out among a multiracial workforce of 5677 staff aged 40 to 64 years at worksites in Auckland and Tokoroa to determine the prevalence of diabetes mellitus and impaired glucose tolerance (IGT). The prevalences of diabetes mellitus and IGT were both similar for men and women, but increased with age. The relative risks for diabetes mellitus and for IGT were both inversely associated with gross annual household income, independent of age and ethnicity, being 1.61 (95% Cl = 1.10, 2.37) and 1.80 (95% Cl = 1.21, 2.67) respectively, in the lowest income group (less than $30,000) compared with the highest (greater than $40,000). Compared with Europeans, the relative risk of diabetes mellitus was significantly increased among Maori (3.63; 95% Cl = 2.48, 5.32), Pacific Islanders (2.34; 95% Cl = 1.50, 3.66) and Asians (5.97; 95% Cl = 2.61, 13.65), after controlling for age, income and body mass index. The increased prevalence of diabetes mellitus among Maori and Pacific Islanders, but not in Asians, could be partly attributed to their increased levels of obesity compared with Europeans. However, other factors, in addition to obesity, explain the increased diabetes prevalence in nonEuropean groups. PMID- 1923083 TI - Waiting lists. PMID- 1923084 TI - Overt neonatal seizures: outcome at one year. AB - Sixty-five infants with seizures in the neonatal period were followed to the age of one year. There were 27 nonsurvivors, with 14 neonatal deaths from causes directly related to the initial neurologic insult, and 13 postneonatal deaths, eight related to neurologic sequelae and five to unrelated causes. Twenty-four (63.2%) of the survivors were neurologically normal, while five (13.2%) had seizures at age one year. Multivariate stepwise analysis identified low birthweight (p less than 0.01) and the number of anticonvulsants used to control the initial seizure(s) (p less than 0.05) as being significantly associated with nonsurvival and neurodevelopmental sequelae amongst the survivors was significantly associated with the duration of initial seizure (p less than 0.05). PMID- 1923085 TI - Evaluation of a rapid diagnostic test for group A beta-haemolytic streptococcus in general practice. AB - OBJECTIVE: to assess the efficacy of Abbott Testpack Strep A compared with throat culture for the diagnosis of group A beta-haemolytic streptococcus in general practice. METHODS: one hundred and fifty-four specimens were obtained from general practices in selected regions, and were tested for group A beta haemolytic streptococcus using both Abbott Testpack Strep A and throat culture. RESULTS: sensitivity of the rapid diagnostic test was 79.4%, specificity 93.3%. The negative predictive value of the test was 94.1%; the positive predictive value 77.1%. CONCLUSION: maximum cost effectiveness is achieved, with respect to short term costs and benefits, by diagnosing and treating solely on the basis of Abbott Testpack Strep A results. When possible complications are taken into consideration, initial testing by Abbott Testpack Strep A, followed by confirmatory laboratory testing of negative Testpack results becomes a feasible alternative. PMID- 1923086 TI - Endoscopic management of bile duct stones at Auckland Hospital in 1988 and 1989. AB - OBJECTS: to define the role of endoscopic management of bile duct calculi in a tertiary referral institution. METHODS: an unselected series of 466 patients presenting for ERCP over a two year period were reviewed and 103 patients with bile duct calculi identified. The results of endoscopic management of these patients is reviewed. RESULTS: endoscopic sphincterotomy was successful in 98% of patients, and resulted in clearance of calculi from the bile duct in 75%, and in a further 8% symptoms were successfully controlled by sphincterotomy with or without endoprostheses, despite residual calculi. Seventy-nine percent of the patients with choledocholithiasis were successfully managed endoscopically, minor complications occurring in 16% which were significant in only 4%, with no procedure related mortality. CONCLUSIONS: endoscopic sphincterotomy provides a safe and effective means of managing bile duct calculi, even if stone extraction cannot be completed. PMID- 1923087 TI - A paediatric day ward: parental expectations, perceptions, and satisfaction. AB - OBJECT: to evaluate an acute paediatric day ward service from the parental perspective. METHODS: parental interview using structured questionnaire. RESULTS: overall satisfaction with the day ward concept and practice was high. Specific delays in the admission and management process were highlighted, as were concerns over practical issues such as parking facilities, pharmacy support, and perceived staff workload. CONCLUSIONS: the broad aims of the unit are being met. Areas for potential improvement are defined and discussed. PMID- 1923088 TI - Mycobacterium fortuitum pneumonia--treatment with enoxacin and cotrimoxazole. PMID- 1923089 TI - The safety of triazolam (Halcion) PMID- 1923090 TI - Molecular screening of cystic fibrosis patients. AB - A method for the direct direction of the delta F508 mutation in the cystic fibrosis gene has been developed and applied to the analysis of over 280 individuals including 104 individuals with cystic fibrosis. This technique allows the rapid analysis of DNA from whole blood, Guthrie card blood spots, and the antenatal diagnosis of cystic fibrosis from chorionic villus biopsy samples. Based on these analyses, the delta F508 mutation is found in 77.88% of cystic fibrosis chromosomes in New Zealand cystic fibrosis patients. Thus this test can be used to establish a direct DNA diagnosis in over 60% of cystic fibrosis patients. Approximately a further 30% are heterozygous for this mutation. PMID- 1923091 TI - Lactose malabsorption and calcium intake as risk factors for osteoporosis in elderly New Zealand women. AB - OBJECTS: to evaluate the prevalence of lactose malabsorption and to assess dietary calcium intake, in elderly New Zealand women with hip fractures, in age matched case controls without hip fractures drawn from general practice, and in healthy young women. METHODS: lactose malabsorption was assessed by measuring breath hydrogen after a 50 g oral lactose tolerance test. Dietary calcium was estimated from a food frequency questionnaire. RESULTS: the elderly fracture cases (n = 15), and their elderly controls (n = 16), showed a similar (60% and 63% respectively), but significantly higher prevalence (p less than 0.001), of lactose malabsorption than young women (12%, n = 50). Dietary calcium intake was similar in lactose absorbers and malabsorbers. CONCLUSIONS: malabsorption of lactose occurs commonly in elderly New Zealand women but is scarce in young adults. A high prevalence of lactose malabsorption may be a risk factor for exacerbation of type II osteoporosis in the elderly. PMID- 1923092 TI - Opportunistic mycoses--some priorities for the 90s. PMID- 1923093 TI - Tuberculosis among long term hospital residents: report of a recent outbreak. AB - Following the diagnosis of a case of miliary tuberculosis in a ward of 30 psychogeriatric patients, a further seven patients required treatment for active tuberculosis, and an additional four received prophylactic therapy. Tuberculosis contributed significantly to the deaths of three patients during the outbreak. This report highlights the particular risks of both reactivation and primary tuberculosis among geriatric patients receiving long term residential care. Late diagnosis contributed to the extent of the outbreak. Previous studies indicate that occult transmission of tuberculosis is relatively common in this group. An active policy of screening and prophylactic treatment is advised. PMID- 1923094 TI - The BACTEC TB system in the laboratory diagnosis of mycobacterial infection. AB - OBJECT: to compare the BACTEC TB system with our conventional multimedia system for the isolation of mycobacteria from clinical specimens. METHODS: specimens received over a two year period were cultured into BACTEC 12B vials and onto a variety of solid and liquid media routinely used by us for the isolation of mycobacteria. Cultures were observed regularly for bacterial growth, and examined for the presence of mycobacteria by acid fast microscopy. All results were recorded. At the end of the two year period the results for the two methods were compared. RESULTS: of the 4443 specimens cultured by both methods, 260 were positive for mycobacteria. Sensitivity and specificity were 88.31% and 99.35% respectively for the BACTEC, and 84.41% and 99.96% respectively for our routine multimedia system. Tuberculosis was confirmed by the BACTEC TB system in six patients who were otherwise culture negative. One of these patients had tuberculous meningitis. Three patients culture positive for M tuberculosis by our routine method, were negative by the BACTEC. Twenty-nine false positive cultures were detected, 27 by the BACTEC TB system alone. CONCLUSIONS: the BACTEC TB system is a rapid and sensitive system for the detection of mycobacteria in clinical specimens, and has proved to be a useful adjunct to our routine multimedia system. However, decreased specificity, particularly with lower respiratory tract specimens, means that positive results from these sites can be reported less confidently when they are detected by the BACTEC TB system alone. This negates some of the advantages of the BACTEC TB system for the detection of mycobacterial disease of the lungs. PMID- 1923095 TI - Fetomaternal haemorrhage with decreased fetal movements and a sinusoidal fetal heart rate pattern. PMID- 1923096 TI - The hospital transfusion committee: a step towards improved quality assurance. AB - Quality assurance has an important contribution to make in the judicious use of scarce resources. Auckland Hospital has established a transfusion committee because there was an escalating usage of blood and blood products which are expensive prescription medicines. A pilot audit of red cell transfusions indicated that 29% of red cell transfusions may have been unnecessary. A wide range of initiatives at Auckland Hospital has reduced blood product usage. Inappropriate use of blood carries an opportunity cost and may subject patients to unnecessary risk of reactions, including potential disease transmission. Strategies which need to be employed by transfusion committees include the introduction of clinical audit, physician education, restrictions on availability, and clinical budgeting. It is recommended that transfusion committees be set up in all major hospitals. PMID- 1923097 TI - Preoperative outpatient consultation in private anaesthetic practice. AB - To assess the value of preoperative anaesthetic consultations done on an outpatient basis, questionnaires were sent to 150 consecutive private patients who had been seen during the previous six months. Replies were received from 72%, and of these, 88% found the visit to be beneficial, whilst 2% were critical of the practice. Twenty-three percent did not know that anaesthetists were medically qualified. A retrospective audit of a further 100 patients revealed that 52% of patients had had their preoperative management altered to some degree as a consequence of the appointment. Based on his own experiences and the comments received from patients, the author believes this practice should be more widespread. PMID- 1923098 TI - Multiple authorship. PMID- 1923099 TI - Yersinia infected blood. PMID- 1923100 TI - Food for New Zealanders: high iodine, low selenium status. PMID- 1923101 TI - Should we still be doing D & C? PMID- 1923102 TI - Trends in nonmelanoma skin cancer mortality. AB - Nonmelanoma skin cancer mortality rates for recent decades show a biphasic pattern: from 1950-65 rates decreased; from 1966-86 rates increased. Age standardised mortality rates for 35-74 year old males increased from 1.6 (95% CI, 1.3-1.9) deaths per 100,000 person years in 1966-72 to 2.3 (95% CI, 2.0-2.5) deaths per 100,000 person years in 1980-86. Rates in women were lower but showed a similar percentage increase (46%), between these periods, to that observed for men (44%). The increased mortality from 1966 was presumably a result of increased ultraviolet exposure. PMID- 1923103 TI - Acute myeloid leukaemia: results of the New Zealand AML-1 study. The Leukaemia Study Group of the New Zealand Society for Haematology. AB - The New Zealand Acute Myeloid Leukaemia (AML-1) study ran from 1985 to 1988. Ninety-two patients with acute myeloid leukaemia between the ages of 13-65 were entered. Remission induction treatment consisted of cytosine arabinoside (Ara-C) 100 mg/m2 12 hourly for seven days and daunorubicin (DNR) 45 mg/m2 daily for three days. Fifty-six patients entered remission (61%). The patients were randomised at diagnosis to receive either three further courses of Ara-C (five days) and DNR (two days) in the same dosage or three courses of VP16 100 mg/m2 daily for five days and one dose of mAMSA of 200 mg/m2 as postremission consolidation. No difference in survival between these two consolidation treatments was seen (p = 0.96). The overall survival of the original 92 patients is 13% with a minimum follow up of two and a half years. However, for those patients solely treated with the trial protocol, disease free survival at 2% is poor. The poor long term results could reflect the relatively low intensity consolidation treatment used in this study. However, since a majority of patients presenting in New Zealand with acute myeloid leukaemia between these ages were entered into the trial, the results could also reflect the relative lack of selection bias which affects many published studies of acute leukaemia treatment. PMID- 1923104 TI - Health proposals and NZMA. AB - NZMA welcomes the opportunity for public debate over the degree to which the community should fund health care for all. It views the attempts to improve the integration of the health service with interest and hopes to enter a vigorous debate with government to ensure that the detailed proposals yet to be formulated will achieve the purpose we both desire. But the association is disappointed to see policies promoted that are often so reliant upon anecdote and a naive theory of economics. It is disappointing to see health policy altered so radically with so little analysis of facts. Waiting lists, as an example, are analysed with no statement of what proportion of hospital admissions are represented by waiting list patients. Part charges have been introduced in areas where there is no experimental justification for supposing that they will usefully alter patient behaviour. A more sophisticated approach is required. Some change must be sought in the so-called nonnegotiable part of the proposals. PMID- 1923105 TI - Neonatal septicaemia: a changing picture? AB - The incidence, aetiologic organism and mortality associated with neonatal septicaemia were retrospectively reviewed over a seven year period (June 1983 to July 1990). Trends with time were evaluated by dividing the study period in half. Although there was no significant change in the incidence of septicaemia during the study period (3.59 vs 3.40 per 1000 livebirths), there was a marked increase in the numbers of very low birthweight infants developing early onset group B streptococcal sepsis and an associated increase in mortality. PMID- 1923106 TI - Patient evaluation of otolaryngology department service at Christchurch Hospital. AB - One hundred and four consecutive patients seen in the ENT department for consultation and inpatient treatment completed a structured questionnaire at their first postoperative (or posttreatment) outpatient clinic appointment. The aims of the survey were to ascertain the patients opinions and perceptions regarding the ENT department service in a variety of areas. Satisfaction was high in areas of medical and nursing care and with the information given regarding treatment. The major area of dissatisfaction was with waiting times, particularly waiting times at appointments during ENT outpatient clinics. PMID- 1923107 TI - Osteoid osteoma of the os calcis: difficulties in diagnosis. PMID- 1923108 TI - Medical involvement in management: a natural corollary of the budget reforms? PMID- 1923109 TI - Cervical screening coverage. PMID- 1923110 TI - AIDS today. PMID- 1923111 TI - Hot flushes in women. PMID- 1923112 TI - Views from the bedside. PMID- 1923113 TI - The core's the limit. PMID- 1923114 TI - New unity for Dutch nurses. Interview by Kathy Stodart. PMID- 1923115 TI - Unsung heroes. Relishing the independence. Interview by Kathy Stodart. PMID- 1923116 TI - Who's the victim? PMID- 1923117 TI - Blowing the whistle. PMID- 1923118 TI - Update on credentialing. PMID- 1923119 TI - Nursing case conferences on a psychiatric unit. PMID- 1923120 TI - More information on the "Hospice 6". PMID- 1923121 TI - Stress in the head nurse role. PMID- 1923122 TI - Career ladders: position enrichment vis-a-vis tenure. PMID- 1923123 TI - Evaluating nursing productivity in the emergency department. PMID- 1923124 TI - Building teams through solving problems. PMID- 1923125 TI - Mother vs. child--a legal controversy. PMID- 1923126 TI - Medicaid--at the brink. PMID- 1923128 TI - A pragmatic concern. PMID- 1923127 TI - Computer-based patient records, Part I: the Institute of Medicine's Vision. PMID- 1923129 TI - First-line manager skills: perceptions and performances. PMID- 1923130 TI - Communications: distributing oncology outpatient telephone calls. PMID- 1923131 TI - Nursing wellness: developing staff behaviorally. PMID- 1923132 TI - A strategy for budgeting obstetrical costs. PMID- 1923133 TI - Collaborating to develop a student intern program. PMID- 1923134 TI - Health effects of visual display terminals. PMID- 1923135 TI - Sick child care program. PMID- 1923136 TI - Nursing attire: the public's preference. PMID- 1923137 TI - A family medicine teaching unit. PMID- 1923138 TI - From OB/GYN to women's programs. PMID- 1923139 TI - Managing in a pressure cooker. PMID- 1923140 TI - Translating ethics into practice in the workplace. PMID- 1923141 TI - Establishing clinical self-confidence. PMID- 1923142 TI - Mandated continuing education deserves professional attention and input. PMID- 1923143 TI - AIDS article con... PMID- 1923144 TI - Are peer review decisions still binding? PMID- 1923145 TI - Dentistry's oxymorons. AB - Confusion in language results in perplexity in relationships between doctor and patient, as well as threatening the consanguinity of the doctor to his fellow doctor. This article explores the common use of self-contradictory terms in the field of dental orthopedics and anesthesia-sedation in particular, and the unethical, verbal de-specialization of the dental specialist in general. It scrutinizes common dental advertising malpractices. PMID- 1923146 TI - Modern concepts in crown preparation. AB - The preparation of teeth for full coverage is one of the most abused procedures in fixed prostheses. It is fallacious to discard precision preparations on the grounds that they will not be visible once the crown is constructed. In truth, what takes place in the preparation phase of crown and bridge construction determines the quality of the final restoration. PMID- 1923147 TI - The role of dental schools in future film selection. PMID- 1923148 TI - To "take arms against a sea of troubles". PMID- 1923149 TI - Expert systems--a role in nuclear medicine? PMID- 1923150 TI - Combined 67Ga citrate and 99Tcm-human immunoglobulin imaging in human immunodeficiency virus-positive patients with fever of undetermined origin. AB - Patients infected with the human immunodeficiency virus (HIV) suffer from serious and life-threatening infections. These patients often present with pyrexia but without localizing signs. Despite its high sensitivity in identifying focal infection 67Ga citrate scintigraphy lacks specificity; lymphoma and solid tumours may also be imaged. This presents particular problems in HIV-positive patients with pyrexia where the differential diagnosis is often between infection and lymphoma. In an attempt to improve the specificity of radionuclide imaging in these patients a combination of 67Ga citrate and the new agent 99Tcm-labelled human immunoglobulin (99Tcm-HIG) was used in 25 patients who were sequentially imaged with the two agents. Fourteen patients had 29 sites of microbiologically confirmed infection; 67Ga citrate identified 27 sites and 99Tcm-HIG identified 16 sites. Seven of the nine sites visualized with 99Tcm-HIG, but positive with 67Ga citrate, were intrathoracic. Abnormal concentration of 67Ga citrate, not due to infection, occurred at eight sites; five lymphoma, one gout, one recent fracture and one patient with prominent bone marrow islands. 99Tcm-HIG showed increased concentration of tracer in only one of the patients with lymphoma. A combination of 67Ga citrate and 99Tcm-HIG imaging in HIV-positive patients with pyrexia of unknown origin enables a differentiation between infection and lymphoma to be made more readily. The poor sensitivity of 99Tcm-HIG in the chest will limit its sole use in this patient group. PMID- 1923151 TI - Kinetics and biodistribution in relation to tumour detection with 111In-labelled OV-TL 3 F(ab')2 in patients with ovarian cancer. AB - The biological behaviour of 111In-labelled OV-TL 3 F(ab')2 was studied in 22 patients with suspected ovarian cancer. After i.v. injection with 140 MBq 111In OV-TL 3 F(ab')2 (1 mg) blood samples were taken up to 96 h and urine and faeces were collected throughout the whole study. At surgery, 5 to 7 days post injection, primary and metastatic tumour tissues, as well as fragments of several normal tissues, were removed and 111In uptake was measured. Blood activity disappeared with half-life values of 6.1 +/- 1.1 and 17.9 +/- 6.5 h. Within 96 h excretion in urine and faeces was 16.1 +/- 2.0% i.d. (mean +/- S.D.) and 3.1 +/- 1.9% i.d., respectively. Mean tissue uptake, expressed as % i.d. kg-1 was 3.9 +/- 1.0 for primary tumour, 11.5 +/- 5.0 for liver and 0.4 +/- 0.1 for several normal background tissues. Higher tumour uptake correlated with a higher detection rate at immunoscintigraphy. However, no strict correlation was found between the amount of tumour uptake and the expression of the monoclonal antibody defined OA3 antigen. Quantitation of organ activity, using region of interest analysis, resulted in mean peak organ activities for the liver of 16% i.d., spleen 9% i.d. and kidney 4% i.d. Distribution data indicate that besides specific antibody antigen interaction several other mechanisms play a role in uptake in tumour and other tissues. PMID- 1923152 TI - Assessment of 99Tcm-HMPAO tumour scintigraphy using VX-2 tumours implanted in a lower limb muscle of rabbits. AB - Tumour scintigraphy using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) was investigated in VX-2 tumours implanted in the muscles of the lower legs of rabbits to assess the feasibility of using this agent clinically for this procedure. On the time-activity curves for 99Tcm-HMPAO in the tumour, an initial peak and a subsequent decrease of radioactivity immediately after the initial peak were observed, while there was a slow, gradual decrease of activity over the next hour. The tumour/normal muscle ratio of HMPAO activity during this period was high and constant, and was independent of time. Comparison of the static images of 99Tcm-HMPAO with angiography and histological findings suggests that the tumour image of 99Tcm-HMPAO reflects tumour blood perfusion. These findings indicate that the distribution of 99Tcm-HMPAO on static images can provide a qualitative assessment of the perfusion of the tumour, despite the limitations of this tracer for quantifying tumour blood flow due to its early efflux from the tumour. PMID- 1923153 TI - 99Tcm-HMPAO-labelled leucocytes for bone marrow scintigraphy and evaluation of skeletal lesions. Comparison with 99Tcm-HSA colloid results. AB - Bone marrow scintigrams obtained 2-6 h and/or 20-24 h after injection of 99Tcm HMPAO-labelled leucocytes (LeuSc) in 16 patients (seven males, nine females, average age 57 years, either with benign or malignant haemopathy, or with benign or metastatic skeletal diseases) have been compared to corresponding pictures obtained 20 min after injection of 99Tcm-labelled human serum albumin nanosized colloids (NanSc, performed within a week thereafter). Overall distribution of the colloids and of the labelled leukocytes at the level of the bone marrow appeared to be the same. Fresh vertebral fractures as well as metastatic lesions of the axial skeleton appeared as cold defects in both investigations. Fractures of the ribs as well as one metastatic lesion involving one trochanter could not be identified. Although all seven lesions involving Th9 to L4 could be clearly investigated with LeuSc, only three could be recognized with NanSc. It is concluded that, in patients with cancerous diseases, LeuSc is better than NanSc in demonstrating lesions in the case of dubious conventional osseous scintigrams as well as in the case of neurological or skeletal symptoms at the level of the lumbar and/or low thoracic regions. PMID- 1923154 TI - Relationship between 99Tcm-MDP uptake and bone mineral density in patients with prostatic carcinoma. AB - Seventeen men with prostatic carcinoma were investigated with quantitative bone scintigraphy and quantitative computed X-ray tomography before orchiectomy and up to 6 months after this operation. The uptake of 99Tcm-labelled methylene disphosphonate (99Tcm-MDP) and bone mineral density (BMD) were determined for each vertebra from Th10 to L4. Ten patients had normal scintigrams. No change in MDP uptake or BMD was seen after 6 months in these patients. Of the seven patients with abnormal scintigrams, one patient had a clinical sign of progression with an increase in both MDP uptake and BMD. The remaining six patients showed stable or improved clinical status. For their abnormal vertebrae a decrease in MDP uptake was seen, while BMD varied in different ways after 6 months. For the normal vertebrae in these patients with metastatic involvement, no change in MDP uptake was seen. However, the BMD values showed a decrease, indicating a generalized increase in bone resorption at sites distant from the metastases. PMID- 1923155 TI - Comparison of 99Tcm-labelled monoclonal anti-granulocyte antibody and 111In labelled IgG for the detection of focal sites of infection in rats. AB - The abilities of 99Tcm-labelled monoclonal anti-human granulocyte antibody (AGAb) and 111In-labelled nonspecific polyclonal human immunoglobulin (IgG) to localize at focal sites of inflammation were compared in rats with deep thigh infection due to E. coli. The radiolabelled antibodies were coadministered followed 4-6 and 24 h later by imaging and biodistribution studies. At 4-6 h after injection, the target to background ratio (T/B, lesion to contralateral leg) and percentage residual activity (% RA, counts in the lesion/total body counts) were nearly identical for both antibody preparations. At 24 h, T/B and % RA increased significantly (P less than 0.001) for both proteins but differences between the agents were not significant. In vitro analysis of the binding of AGAb and human polyclonal IgG to rat granulocytes showed a low level of binding with both agents. These results suggest that the primary mechanism of localization, by either antibody preparation in this model, is not antigen related. 111In-labelled nonspecific human IgG and 99Tcm-AGAb are equivalent reagents for the detection of focal sites of infection in the rat. PMID- 1923156 TI - Importance of collimator selection for quantitative 131I scintigraphy. AB - Aberrant 131I orthoiodohippurate renal plasma flow values were obtained when our image-based method was moved from an old to a new gamma camera. We suspected inadequate collimation as the reason for this problem because we observed increased septal penetration and scatter. Camera effects were largely eliminated because both our old and new cameras had 1/2'' thick crystals. We report here the effects of two high and three medium energy collimators upon the fraction of syringe image count beyond the syringe image, and upon the correlation of these non-image count fractions with geometric collimator parameters. We also report the effects of these same collimators upon kidney-to-background count ratios, using patient relevant abdominal phantoms. The percentage counts beyond the syringe image varied from 33 to 57%. The phantom kidney-to-background ratios varied from 3.7 to 2.0. We conclude that image-based quantitative measurements are strongly dependent on collimator selection. The data also provide a user basis for collimator evaluation, selection and design, and have implications for 131I and 111In antibody imaging. PMID- 1923158 TI - Immune thrombocytopenic purpura in pregnancy: a reappraisal of management. AB - Management and, particularly, mode of delivery of the pregnant patient with immune thrombocytopenic purpura (ITP) are controversial. We reviewed our experience with 31 pregnancies in 25 women with ITP over a 10-year period. Fourteen infants were born vaginally and 18 by cesarean. Six major complications occurred among mothers delivered by cesarean, whereas none occurred among those born vaginally (P = .028). Three of 32 infants were born with moderate thrombocytopenia (platelet count 51-100 x 10(9)/L) and two with severe thrombocytopenia (platelet count 50 x 10(9)/L or less); there were no clinically significant complications in these infants. No maternal characteristic could be used to predict the neonatal platelet count. In an analysis of 474 infants of mothers with ITP reported in the literature and including the present series, 10% were born with moderate thrombocytopenia and 15% with severe thrombocytopenia. The overall rate of intracranial hemorrhage in newborns with moderate or severe thrombocytopenia was 3%. No significant association was found between the rate of intracranial hemorrhage and delivery mode for moderately and severely thrombocytopenic neonates together (weighted odds ratio 1.69, 95% confidence interval 0.14-44.6) or for those with severe thrombocytopenia (crude odds ratio 1.38, 95% confidence interval 0.07-84.67). We conclude that the mode of delivery may not affect the rate of intracranial hemorrhage in thrombocytopenic newborns. PMID- 1923157 TI - Perinatal outcome in renal allograft recipients: prognostic significance of hypertension and renal function before and during pregnancy. AB - With more renal allograft recipients becoming pregnant, it is important to refine existing pre-pregnancy assessment criteria and to identify other factors influencing perinatal outcome. We analyzed gestational renal response and acute or chronic hypertension in relation to perinatal outcome for 22 pregnancies that continued beyond 28 weeks' gestation in 17 allograft recipients (mean age 27 years, range 20-40) transplanted between 1967-1987. Before pregnancy, all had plasma creatinine of 1.62 mg/dL or less and 24-hour creatinine clearance of 39 mL/minute or greater. Six pregnancies were to four women on antihypertensive therapy. Mean arterial pressure (MAP), antihypertensive therapy, plasma creatinine, and 24-hour creatinine clearance were recorded before and during pregnancy. Perinatal outcome was adverse in ten pregnancies: five stillbirths, four growth-retarded infants, and one neonatal death, whereas 12 pregnancies had satisfactory perinatal outcome. Early-pregnancy increments and late-pregnancy decrements in renal function were identical in both groups. Mean arterial pressure was significantly higher at 16-28 weeks in women having adverse outcomes. Hypertension (MAP above 107 mmHg) occurred in 16 pregnancies (73%); it appeared before 28 weeks in seven and was invariably associated with adverse outcome. Hypertension appeared after 28 weeks in nine women and was associated with adverse outcome in only two cases. Five of six pregnancies in women who were on pre-pregnancy antihypertensive therapy ended in adverse outcome. It can be concluded that renal function was identical in pregnancies having adverse or satisfactory perinatal outcome, whereas hypertension before or during early pregnancy, albeit apparently satisfactorily controlled, appeared to be associated with adverse perinatal outcome. PMID- 1923159 TI - Anticardiolipin antibodies in patients with recurrent pregnancy wastage: treatment and uterine blood flow. AB - The interest in autoimmune pregnancy loss has increased recently with the discovery of the association between the presence of antibodies to phospholipids and cardiolipin and habitual abortion. To evaluate the prevalence of anticardiolipin antibodies in patients with recurrent fetal loss and the effect of low-dose aspirin and corticosteroid treatment, we examined 67 women for anticardiolipin antibodies with an enzyme-linked immunosorbent assay. Increased levels of anticardiolipin antibodies were found in 34 of these women (50.7%) and in none of 12 normal pregnant controls. Seventeen of these 34 patients conceived and were treated with aspirin, 100 mg/day, and fluocortolone, 10 mg/day. Twelve gravidas reached term, all delivering live infants with good Apgar scores and normal birth weights. Three others delivered prematurely, two of them because of premature rupture of membranes and the other because of severe fetal growth retardation. This latter woman delivered at 31 weeks, and the 1000-g infant died neonatally. The neonatal survival rate was 82% in the treated patients, versus 18% in the same group of subjects in their previous, untreated gestations. The umbilical artery resistance index of the treated subjects was not different from that of anticardiolipin-negative hypertensive women who did not receive aspirin and corticosteroid therapy. However, the uterine artery resistance index was significantly lower in the hypertensive treated group than in the untreated group. Whether this difference reflected a beneficial effect of low-dose aspirin and corticosteroid therapy on pregnancy outcome and survival rate remains to be evaluated. PMID- 1923160 TI - Human versus animal insulin in the management of insulin-dependent diabetes: lack of effect on fetal growth. AB - It is generally accepted that the human placenta is impermeable to free insulin and that insulin present in the fetus is entirely of fetal origin. A recent study suggested that antibody-bound animal insulin crosses the placental barrier and may exert direct effects on fetal growth. We hypothesized that mothers with insulin-dependent diabetes treated with animal insulin would have infants with higher birth weights and ponderal indices compared with mothers treated with human insulin. We studied 209 mothers with insulin-dependent diabetes who were enrolled in our program and who delivered after 28 weeks' gestation: 170 were treated with animal insulin and 39 with human insulin. There were no differences between the groups in the mean birth weight (adjusted by gestational age at delivery) or ponderal index of the infants. The rate of macrosomia (birth weight greater than the 90th percentile for gestational age or ponderal index above 2.85) was similar in both groups. The sample size was adequate to yield a power of 80% to detect a difference between groups of 179 g or more in birth weight and 0.1 g/cm3 in ponderal index. We suggest that the type of insulin (animal versus human) used by the pregnant insulin-dependent diabetic mother has no bearing on fetal weight gain. PMID- 1923161 TI - Screening for illicit drug use in a military obstetric population. AB - The purpose of our investigation was to determine the prevalence of illicit drug use within our socioeconomically heterogeneous obstetric population, in order to assess the need for institution of universal screening. Five hundred consecutive new obstetric registrants had urine collected for routine culture. Following removal of a small aliquot of urine for culture, the samples were sent to the Armed Forces Institute of Pathology, Division of Forensic Toxicology. Each specimen was screened for the presence of alcohol, cocaine metabolites, cannabinoids, opiates, and amphetamines using fluorescent polarization immunoassay techniques. All positive screening tests were confirmed by gas chromatography mass spectrometry. Thirty samples were either lost in processing or of insufficient quantity to test. Five of the 470 samples (1.06%) tested were positive. One subject was taking prescription narcotics, so the correlated prevalence was 0.85%. Three tested positive for tetrahydrocannabinol and two for opiates. Analysis of our data demonstrates that our obstetric population has a significantly lower prevalence of illicit drug use than other populations reported previously (P less than .01). We recommend that each institution providing obstetric services determine its specific prevalence of illicit drug use. PMID- 1923162 TI - Computerized fetal heart rate analysis in labor. AB - Observer variation in visual analysis of fetal heart rate (FHR) records is reportedly high, but can be avoided by computerized numerical analysis. The FHRs of 394 women in labor at 37 or more weeks' gestation were recorded on-line and analyzed to examine how different patterns related to outcome, as judged by umbilical arterial base deficit or Apgar score on delivery. The range of normality and the diversity of patterns of those delivered without acidemia were great. Late decelerations were of poor prognostic value. There was an increase in FHR variation during labor averaging 40%. In this preliminary study, conventional attributes of the FHR, alone or in combination, did not predict metabolic acidemia. Epidural analgesia in 240 women was identified as a confounding variable that significantly affected FHR patterns without influencing the condition of the infant at birth. It was associated with a higher FHR, less FHR variation and fewer decelerations, primiparity, longer labors, more operative deliveries, and a threefold greater cesarean rate. The rise in basal FHR, perhaps due to a rise in maternal temperature, may partly explain the high intervention rate in those without fetal acidemia. PMID- 1923163 TI - Magnesium tocolysis and neonatal bone abnormalities: a controlled study. AB - This study was conducted to investigate the relationship between maternal administration of intravenous (IV) magnesium sulfate and radiographic abnormality of neonatal long bones. Eleven neonates in the exposed group were born to mothers who had received IV magnesium tocolysis for more than 7 days. Two gestational age matched unexposed neonates were selected for each member of the exposed group. Initial chest radiographs of exposed and unexposed neonates were reviewed in random sequence by a pediatric radiologist who was blinded to exposure status. On evaluation of the proximal humeri, six neonates had radiographic abnormalities consisting of transverse radiolucent and/or sclerotic bands; all six were in the exposed group. The difference in radiographic findings between the exposed and unexposed groups was statistically significant (P less than .001). These results support the existence of a causal relationship between prolonged IV magnesium tocolysis and abnormal fetal bone mineralization. Further study is needed to elucidate the mechanism and clinical significance of these bone changes. PMID- 1923164 TI - Amniotic fluid glucose concentration as a marker for intra-amniotic infection. AB - This study evaluated the use of amniotic fluid (AF) glucose concentration as a rapid indicator of intra-amniotic infection. Amniotic fluid glucose concentrations were measured in 86 pregnancies and compared with AF cultures. There were 14 positive cultures with a mean AF glucose of 7.1 mg/dL (range 1-24) and 72 negative cultures with a mean AF glucose of 30.4 mg/dL (range 5-66), a significant difference (P less than .001). An AF glucose of less than or equal to 5 mg/dL had a positive predictive value of 90%; an AF glucose of greater than 20 mg/dL had a 98% negative predictive value. Amniotic fluid glucose can be obtained rapidly and inexpensively, and may be of use in the diagnosis of intra-amniotic infection. PMID- 1923165 TI - Morbidity associated with prenatal disruption of the dividing membrane in twin gestations. AB - We report eight cases of intrauterine rupture of the dividing membranes in diamniotic twin gestations and the resulting perinatal morbidity and mortality. The poor outcomes associated with these intrauterine amniotic ruptures included fetal and neonatal death secondary to cord entanglement, preterm rupture of the membranes, preterm labor and delivery, and amniotic band syndrome. The overall perinatal mortality rate was 44% (seven of 16), and the mean gestational age at delivery was 29 weeks (range 22-34). Possible etiologies for this intrauterine diamniotic rupture include fetal trauma to the dividing membranes, amniocentesis, infection, and developmental disturbances. A new theory is examined to explain the surviving twin's morbidity associated with intrauterine death of the co-twin. This study suggests that intrauterine rupture of diamniotic twin membranes carries a perinatal mortality consistent with that of true monoamniotic gestations and that, in fact, this entity may be more common than previously thought. Finally, a suspected monoamniotic gestation cannot be ruled out by the historic presence of a dividing membrane on previous ultrasound examination. PMID- 1923166 TI - Flow-velocity profiles of the fetal aorta and umbilical artery in pregnancies complicated by pregnancy-induced hypertension and fetal growth retardation. AB - Sixty-seven women undergoing ultrasonographic evaluation in the high-risk clinic were randomly recruited to be examined by a newly developed computerized method that presents flow-velocity profiles derived from pulsed Doppler-generated flow velocity waveforms. Each woman had pulsed Doppler flow velocimetry of the fetal aorta and umbilical arteries done. Subjects were either normal controls (N = 20) or had pregnancies complicated by pregnancy-induced hypertension (N = 29), fetal growth retardation (N = 11), or both (N = 7). Distinct patterns of flow-velocity distribution across the fetal aorta and proximal umbilical arteries were identified in the pregnancies characterized by increased placental resistance. At peak systole, normal velocity was maintained only at a narrow area around the center of the vessel, whereas velocity in the rest of the vessel area was markedly reduced. These changes were present in 40 of 47 subjects (85.1%) with complicated pregnancies, whereas 27 of 47 (57.4%) had umbilical artery systolic diastolic ratios above the 95th percentile. No significant differences between normal and complicated pregnancies were seen during diastole. Our findings suggest that increased placental resistance results in a redistribution of velocities within fetal blood vessels, often before maximal end-diastolic velocity is decreased. PMID- 1923167 TI - Transvaginal Doppler assessment of the fetal cerebral circulation. AB - Blood flow velocity waveforms were recorded by pulsed Doppler examination of the fetal internal carotid and middle cerebral arteries using the established transabdominal route as well as a new transvaginal approach. Fourteen normal controls and 11 pregnancies complicated by intrauterine growth retardation were studied. Satisfactory recordings were obtained in all 25 cases. There was a good correlation (R2 = 0.98) between pulsatility index (PI) values obtained transabdominally and transvaginally. The PI in the middle cerebral artery was significantly higher than in the internal carotid artery in both normal and growth-retarded fetuses. Pulsatility in both cerebral vessels was significantly decreased in growth-retarded fetuses when compared with normal controls. The transvaginal route, which produces a coronal section of the fetal brain, allows better distinction between the internal carotid and middle cerebral arteries. Furthermore, signals of equal quality are obtained from vessels in both cerebral hemispheres. Transvaginal scanning of the fetal cerebral arteries is a feasible technique offering an alternative to transabdominal scanning when the latter is hampered by technical difficulties. PMID- 1923168 TI - Duration of incarceration and perinatal outcome. AB - The number of incarcerated women is increasing, thus pregnancy in prison is no longer uncommon. We reviewed the perinatal outcome of 53 women with short-term incarceration (fewer than 90 days) and of 53 women who experienced long-term incarceration (more than 120 days). Poor prenatal care, history of drug abuse, hepatitis, and poor nutrition were more common among the short-incarceration group. Of infants born to short-incarceration women, 32 (60%) were normal, four (7%) stillborn, eight (15%) premature, six (11%) small for gestational age, and four (7%) septic. Women in the long-incarceration group delivered 48 normal infants (91%), whereas two were offspring of diabetic mothers and three were premature. Birth weight for infants born to smokers in the short-incarceration group was significantly lower than that of infants born to smokers in the long incarceration group. Women who suffer short incarcerations experience high perinatal mortality and morbidity. In contrast, those incarcerated longer appear to benefit from better prenatal care, improved nutrition, and a structured environment, and thus a more favorable perinatal outcome. PMID- 1923169 TI - Maternal and neonatal effects of outlet forceps delivery compared with spontaneous vaginal delivery in term pregnancies. AB - Previous retrospective studies have suggested that the prophylactic use of outlet forceps has a beneficial impact on the neonate because it shortens the second stage of labor and decreases the incidence of neonatal hypoxia. The purpose of this study was to compare the immediate maternal and neonatal effects of outlet forceps delivery (N = 165) with spontaneous vaginal delivery (N = 168) in term parturients. Subjects were randomized to the study or control group immediately before delivery. There were 88 nulliparas and 77 multiparas in the forceps delivery group and 90 and 78, respectively, who delivered spontaneously, a nonsignificant difference. There were no significant differences in gestational age, parity, infant birth weight, length of the first and second stages of labor, use of conduction (continuous epidural) anesthesia, decrease in hematocrit values, Apgar scores, or umbilical arterial pH values between the forceps and spontaneous delivery groups. Seventeen infants in the forceps group and 16 in the control group had cephalhematoma, facial bruising, subconjunctival hemorrhage, or scalp abrasion (not significant). No neonate had fractures, nerve palsies, or intracranial hemorrhage (determined by cranial ultrasound). In the nulliparous population, significant differences were found in the use of episiotomy (93 versus 78%) and the incidence of deep perineal lacerations (24 versus 10%) with forceps compared with spontaneous delivery, respectively (P less than .05). No significant differences between the groups were found in multiparas. We conclude that the use of outlet forceps in patients with uncomplicated labor has no immediate effect on the neonate. Furthermore, outlet forceps delivery does not significantly shorten the second stage of labor and is associated with an increased incidence of maternal perineal trauma. PMID- 1923170 TI - Transient hyperprolactinemia in infertile women with luteal phase deficiency. AB - This study was conducted to evaluate the prevalence of transient hyperprolactinemia in infertile women with luteal phase deficiency. One hundred fifty-one luteal phase deficiency patients and 11 controls had serum prolactin (PRL) measured daily for 3-4 days near ovulation. Thirty-three subjects (21.9%) had transient hyperprolactinemia, with PRL above 20 ng/mL for 1 or 2 days, and were studied further. The blood samples of these 33 subjects and of the controls were also analyzed for LH and FSH. Plasma progesterone was measured on the fourth, seventh, and tenth days after ovulation in both groups. The mean (+/- SD) of the mid-cycle integrated LH surge (125.0 +/- 23.0 mIU/mL; N = 26) and the sum of three plasma progesterone levels (23.8 +/- 4.5 ng/mL; N = 21) in the luteal phase deficiency women were significantly (P less than .001) lower than those of the controls (LH 158.7 +/- 13.8 mIU/mL; progesterone 33.8 +/- 6.5 ng/mL). All 33 luteal phase deficiency subjects with transient hyperprolactinemia were treated with bromocriptine at a dose ranging from 1.25-5 mg/day to maintain mid-cycle PRL levels between 5-15 ng/mL. Both the integrated LH surge and the sum of three progesterone levels increased significantly (P less than .05) during bromocriptine treatment, to 142.6 +/- 22.4 mIU/mL (N = 20) and 28.2 +/- 6.2 ng/mL (N = 18), respectively. Fourteen of the 33 patients conceived. The cumulative probability of conception was 31% for six cycles and 45% for 12 cycles of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1923171 TI - Nausea prophylaxis using transdermal scopolamine in the setting of patient controlled analgesia. AB - We evaluated the effectiveness of transdermal scopolamine in patients receiving morphine via patient-controlled intravenous analgesia following intra-abdominal gynecologic surgery. Soon after arrival in the post-anesthesia recovery unit (time 0), patients were randomized either to receive or not receive a postauricular transdermal scopolamine patch. Nausea and vomiting were scored on a 0-3 scale at this time and at 2, 4, 6, and 24 hours. Patients were treated with droperidol as deemed necessary by the primary care nurse. Within 2-4 hours, transdermal scopolamine patients evidenced less nausea and vomiting and required less droperidol than their counterparts who did not receive transdermal scopolamine. A significant decline in the severity of nausea was noted in the transdermal scopolamine group between 2-24 hours; significant inter-group differences were noted for changes in nausea severity during the 0-6-hour and 0 24-hour intervals. Transdermal scopolamine patients evidenced a significant (P less than .05) decrease in the severity of vomiting during the first 2 hours, significantly different from the increase in the non-transdermal scopolamine patients. After the 4-hour assessment, no transdermal scopolamine patients required droperidol; nine doses were administered to the patients who were not given transdermal scopolamine (P less than .05). Thus, transdermal scopolamine therapy appears to be an effective means of treating the nausea and vomiting that are encountered after gynecologic surgery. PMID- 1923172 TI - Determinants of acceptance of routine voluntary human immunodeficiency virus testing in an inner-city prenatal population. AB - Routine voluntary prenatal human immunodeficiency virus (HIV) counseling and testing offer the opportunity to encourage reduction of high-risk behaviors among uninfected women and to identify those women with asymptomatic HIV infection. To characterize the determinants of acceptance of routinely offered and encouraged HIV testing in inner-city parturients in Atlanta, we identified two groups of women, one that declined HIV testing and another that accepted testing. Each group was asked to complete a questionnaire designed to assess the effectiveness of pre-test counseling. During the 7-month study period, 4731 women registered for prenatal care and 4574 (97%) consented to HIV testing. Nearly all women stated that they were not pressured into having HIV testing performed. Women who accepted HIV testing were more likely to be young, black, and single (P less than .001) and less likely to have received education beyond high school (P less than .05). More accepters than decliners thought the HIV counseling session was valuable (97 versus 91%; P = .04); 55% of accepters agreed to antibody testing because of concern about the risk of transmitting HIV infection to their fetus or infant. More accepters than decliners indicated a willingness to have HIV testing in a future pregnancy (74 versus 33%; P less than .001). These data suggest that most inner-city parturients in our institution view routine voluntary HIV counseling as a valuable component of their prenatal care. PMID- 1923173 TI - Ovarian cancer in women with prior hysterectomy: a 14-year experience at the University of Miami. AB - Between 1977-1990, 755 women were evaluated and treated for ovarian cancer at the University of Miami/Jackson Memorial Medical Center. Ninety-five of them (12.6%) had previously undergone hysterectomy with preservation of one or both ovaries. Sixty women (7.9%) had undergone hysterectomies after the age of 40. Review of the literature reveals a 4.5-14.1% incidence of prior hysterectomy in women developing ovarian cancer. Prophylactic oophorectomy in women undergoing hysterectomy at age 40 or older would have prevented 138 of 2632 cases (5.2%) of ovarian cancer in a combined literature series. Applied nationally, such an approach could be expected to prevent over 1000 cases of ovarian cancer annually. We recommend routine prophylactic oophorectomy in all women undergoing hysterectomy after the age of 40. This strategy would have prevented 60 cases of ovarian cancer treated at the University of Miami during the past 14 years. PMID- 1923174 TI - Reduced spinal bone mass in patients with uterine cervical cancer. AB - Bone destruction and hypercalcemia are well-recognized complications in a variety of neoplasms without bone metastasis. Reduction in the volume of trabecular bone has been confirmed by histomorphometric study, but not by bone densitometer. We measured spinal bone mineral densities by dual-photon absorptiometry in 85 patients with invasive uterine cervical cancer and compared them with measurements from 148 control women. When adjusted for age and menopause duration, mean bone mineral density in patients with uterine cervical cancer was 12.8% lower (P = .0003) and age-matched percentiles were 9.1% lower (P = .0003) than in control women. The deficits in bone mineral density and age-matched percentiles were confined to the uterine cervical cancer patients in their fifties, ie, less than 5 years' menopause duration. Serum concentrations of calcium, phosphate, creatinine, and alkaline phosphatase were not different between control women and the patients with uterine cervical cancer. The results suggest that women with uterine cervical cancer have an increased risk of developing osteoporosis. PMID- 1923176 TI - Randomized controlled trials: "it ain't necessarily so". PMID- 1923175 TI - Ciprofloxacin monotherapy for acute pelvic infections: a comparison with clindamycin plus gentamicin. AB - This prospective, randomized controlled study compared the efficacy and safety of ciprofloxacin alone versus a conventional two-drug regimen, clindamycin with gentamicin. The study group included 71 patients hospitalized for pelvic infections such as acute (N = 33) and chronic (N = 8) salpingitis, tubo-ovarian abscesses (N = 11), endometritis (N = 9), septic abortion (N = 3), and other categories (N = 7). Twenty-two of 35 patients on ciprofloxacin and 20 of 36 on clindamycin plus gentamicin had culturable pathogens: gonococci in 28, anaerobes in six, chlamydia in four, and associated pathogens in 19. Complete clinical and bacteriologic cure was achieved in 21 of 22 (95%) in the ciprofloxacin group and 19 of 20 (95%) in the clindamycin plus gentamicin group. The mean duration of intravenous/oral ciprofloxacin therapy was 3.7/7.2 days, and it was 3/6.6 days for clindamycin plus gentamicin. Ciprofloxacin, a new quinolone, appears to be safe as a single-drug therapy and was as effective as the combination of clindamycin plus gentamicin for the treatment of severe pelvic infections requiring hospitalization. PMID- 1923177 TI - The death of Charlotte Bronte. AB - Although her own physician ascribed her death to tuberculosis, later evaluation of Charlotte Bronte's life and work led some observers to conclude that the cause of her death was hyperemesis gravidarum, a pregnancy complication that was ascribed to neurosis and a rejection of her pregnancy and her femininity. A full analysis of Charlotte Bronte's last months casts doubt as to whether she was ever actually pregnant. Evaluation of her final illness suggests that tuberculosis with secondary Addison disease can fully explain her terminal signs and symptoms. PMID- 1923178 TI - Gynevision. PMID- 1923179 TI - Interpreting the literature in obstetrics and gynecology: I. Key concepts in epidemiology and biostatistics. AB - The proper interpretation of research findings in obstetrics and gynecology increasingly requires some understanding of epidemiology and biostatistics. The disciplines of epidemiology and biostatistics are inextricably related; the goal of epidemiology is accurate measurement of the relationship between an exposure and a disease, and statistical methods are required for achieving that objective. Most epidemiologic studies in the obstetrics and gynecology literature can be classified as 1) cross-sectional, 2) case-control, or 3) cohort (follow-up) studies. The 2 x 2 table represents the basic analytic format for all three types of epidemiologic studies. Information from this table can be used to estimate both the magnitude of the exposure-disease relationship and the relative likelihood that chance explains study findings. Accurate measurement of the relationship between an exposure and a disease can be impeded by two major sources of error: bias and chance. In broad terms, biases can be classified as those related to 1) selection, 2) information, and 3) the presence of extraneous variables. Because biases in epidemiologic studies distort measurements, they must be identified, characterized, and, if possible, avoided. When biases cannot be avoided, knowledge of their likely impact on study findings must be assessed. The role of chance is evaluated by statistical testing of the null hypothesis, ie, the hypothesis that two factors are not associated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1923180 TI - Interpreting the literature in obstetrics and gynecology: II. Logistic regression and related issues. AB - The goal of epidemiology is accurate measure of the relationship between an exposure and a disease of interest. The control of covariates of the exposure disease relationship is required to obtain a valid measure. Two types of covariates, confounders and effect modifiers, must be considered. Investigators can design studies to measure and control for the impact of both types of covariates. Design strategies for dealing with covariates include randomization, restriction, and matching. If the impact of a covariate is not eliminated by study design, it must be controlled for during study analysis by use of either stratification or mathematical modeling. Stratified analysis permits an assessment of the exposure-disease relationship for each category of relevant covariates. Although stratification is the best initial approach for controlling covariates, it is often impractical, particularly if more than one or two covariates must be controlled. Multivariate mathematical models are required if multiple covariates are to be controlled. Logistic regression is the mathematical modeling procedure most often used to analyze studies in obstetrics and gynecology. Although there are no uniform rules for building a proper model for regression analysis, useful general strategies are available. It must be emphasized that, though the use of mathematical modeling can control for multiple covariates and thereby improve the chance of obtaining an accurate measure of the exposure-disease relationship, it cannot "fix" data that result from a poorly designed or improperly conducted study. PMID- 1923181 TI - Abdominal-retroperitoneal sacral colpopexy for the correction of vaginal prolapse. PMID- 1923182 TI - The postmenopausal adnexal mass: correlation between ultrasonic and pathologic findings. PMID- 1923183 TI - Mandatory trial of labor after cesarean delivery: an alternative viewpoint. PMID- 1923184 TI - Retrospective study of fetal effects of prolonged labor before cesarean delivery. PMID- 1923185 TI - Evaluation of normal gestational sac growth: appearance of embryonic heartbeat and embryo body movements using the transvaginal technique. PMID- 1923186 TI - The histologic reliability of laser cone biopsy of the cervix. PMID- 1923187 TI - The cost of maternal cocaine abuse: I. Perinatal cost. AB - Although the clinical impact of maternal cocaine abuse has been well documented in recent years, there have been no reports on the direct and indirect costs of such abuse. This study compares hospital charges of a cocaine-abusing population with those of a control group. Ninety-one mother-infant pairs testing positive for cocaine at delivery were compared with a screened drug-free control population matched for socioeconomic status, age, and parity. When compared with controls, cocaine-positive mothers were more likely to deliver prematurely (37 versus 2%) and to have low birth weight (2613 versus 3340 g) or growth-retarded infants (12 versus 0%) with Apgar scores less than 7 at 5 minutes (8 versus 1%), signs of cocaine exposure (63 versus 0%), neonatal intensive care use (30 versus 3%), and extensive hospitalization (11 versus 3 days). As expected, there was a substantial cost difference between the study and control groups. Hospital charges for the labor, delivery, and postpartum care of cocaine-positive mothers in the study group averaged $3608, whereas maternal control charges averaged $3147 (P less than .05). Neonatal charges from the cocaine-positive study group averaged $13,222, whereas control charges averaged only $1297 (P less than .03). Most of the statistically significant differences in perinatal cost between the cocaine-positive and control populations can be traced to the association between cocaine abuse and premature birth. This information should benefit institutions and organizations trying to assess cost-benefit aspects of programs for prevention and treatment of cocaine abuse during pregnancy. PMID- 1923188 TI - Pregnancy in a cohort of long-term partners of human immunodeficiency virus seropositive hemophiliacs. AB - Since 1981, there have been 17 pregnancies in 12 long-term female sexual partners of human immunodeficiency virus (HIV-1)-seropositive hemophilic men at the New England Hemophilia Center. Eleven of 12 women were seronegative for HIV antibody and one was seropositive. Six of the women followed a specific antibody testing schedule for nine pregnancies. This involved antibody testing at specific points before, during, and after pregnancy. All of the seronegative women had at least one negative antibody test at the conclusion of each pregnancy. Fourteen of 16 pregnancies in the seronegative women resulted in live-born infants. The children now range in age from 7 months to 7 years and 8 months, and have no significant medical problems. The woman found to be seropositive at 8 weeks' gestation of her first pregnancy subsequently delivered an infected infant. In this small group, 11 of 12 women at risk for HIV transmission were able to become pregnant and remain seronegative for HIV antibody. Antibody testing during pregnancy gave the women information on which to base reproductive choices. PMID- 1923189 TI - Ultrasound surveillance of the cervix in twin gestations: management of cervical incompetency. AB - Fifty-one consecutive twin pregnancies studied prospectively were compared with 153 consecutive control twin gestations that were concurrently delivered, but chosen retrospectively. Study patients were managed by a protocol that used weekly ultrasound surveillance combined with clinical assessment. Control subjects were not managed by protocol or ultrasound surveillance. Seven of 51 study patients (13.7%) were diagnosed as having cervical incompetency before 30 weeks' gestation (range 18-28 weeks, mean 24). In comparison, 14 of 153 controls (9.2%) delivered before 30 weeks' gestation (range 18-29 weeks, mean 25). The mean cervical length, dilatation, and membrane herniation (funneling) at diagnosis were 1.9, 2.2, and 3.6 cm, respectively, for patients with cervical incompetency. There was a significant difference in perinatal mortality. All study twins survived, whereas nine control subjects delivered at a mean gestational age of 22.7 weeks, with a loss of 17 infants. Life table analysis demonstrated that a significantly greater proportion of controls delivered very low birth weight, premature twins. The use of ultrasound and clinical criteria to select patients for cerclage placement helped prevent birth of the youngest and smallest twins and significantly decreased perinatal mortality in the study group. Routine cerclage placement is not recommended for twin gestations, but multifetal gestations may benefit from ultrasound surveillance for cervical incompetency. PMID- 1923190 TI - The limited usefulness of urine and blood cultures in treating pyelonephritis in pregnancy. AB - Although urine cultures are performed routinely in managing acute pyelonephritis in pregnancy, little is known about the clinical usefulness of these cultures. The same is true for blood cultures. To evaluate their role in managing patients, we reviewed the records of 156 cases to determine to what extent such cultures influenced treatment. Over 90% of urine isolates were sensitive to the initial antibiotic. Most changes in therapy were based on clinical response; only 3% of pre-treatment urine cultures and 2% of blood cultures led to a change in antibiotics. On a nationwide basis, urine and blood cultures cost $10-20 million each year. Our data suggest that more limited use of cultures will simplify management and save money without compromising patient care. PMID- 1923191 TI - Changes in uterine venous prostaglandin F metabolites following intravenous infusion of ritodrine in sheep. AB - The effectiveness of the beta-adrenergic receptor agonist ritodrine as a tocolytic agent is limited by the tachyphylaxis that occurs with its sustained usage. In order to understand the nature of this tachyphylaxis, we investigated the effect of ritodrine on uteroplacental prostaglandin (PG)F2 alpha production in pregnant sheep. Using general anesthesia in five pregnant sheep, we placed catheters in the aorta and vena cava and in the uterine vein from the uterine horn. In random order on different days, we infused ritodrine (4 micrograms/kg/minute) or physiologic saline into the maternal vena cava at a rate of 0.184 mL/minute. Uterine venous and maternal arterial blood was sampled 60 minutes before and immediately before the infusion and then at 60, 120, 180, and 240 minutes during the infusion. After centrifugation, the serum was frozen and then assayed for the metabolite of PGF2 alpha (PGFM). Uterine venous PGFM increased significantly after 60 minutes of ritodrine infusion (mean increase 1.164 ng/mL; P less than .05), and this increase was sustained during the 4-hour infusion. The PGFM gradient across the uteroplacental bed (uterine vein - aorta) was also significantly elevated during the infusion, suggesting a uteroplacental or fetal membrane source of the PG. Saline had no effect on uterine venous PGFM or the PGFM gradient. These results suggest that ritodrine stimulates PGF2 alpha production, and this may contribute to the tachyphylaxis that occurs with ritodrine and limits its long-term effectiveness as a tocolytic agent. PMID- 1923192 TI - Effects of human relaxin on isolated rat and human myometrium and uteroplacental arteries. AB - We investigated the effects of synthetic human relaxin (hRLX-2) on isolated rat and human myometrium and on uteroplacental arteries from term pregnant women. The preparations were mounted in organ baths and isometric tension was recorded. In isolated myometrium from nonpregnant rats, hRLX-2 (10(-10)-10(-7) mol/L) produced concentration-dependent inhibition of contractile activity induced by vasopressin (10(-8) mol/L). In isolated human myometrium from the fundus or isthmus, hRLX-2 (10(-10)-10(-7) mol/L) did not influence spontaneous activity or contractions induced by oxytocin (10(-9) mol/L) and prostaglandin (PG) F2 alpha (10(-5) mol/L). Nor did it influence the tension induced in small intramyometrial arteries by U46619 (10(-7) mol/L), noradrenaline (10(-5) mol/L), and endothelin (10(-9) mol/L); or the tension induced in fetal stem villus arteries by U46619 (10(-7) mol/L), endothelin (10(-9) mol/L), and PGF2 alpha (10(-5) mol/L). The inhibitory effects of hRLX-2 in preparations of rat myometrium were not influenced by the presence of human myometrium in the organ bath or by pre incubation of hRLX-2 with human myometrium. These results suggest that direct inhibitory effects of relaxin may be of minor importance for the regulation of myometrial activity and uteroplacental circulation in term human pregnancy. PMID- 1923193 TI - Perinatal outcome after multifetal reduction to twins compared with nonreduced multiple gestations. AB - The outcomes of twins resulting from multifetal reduction were analyzed to examine whether the outcome was improved over that of triplet and quadruplet pregnancies and similar to that of twin pregnancies not involving multifetal reduction. Maternal and perinatal outcomes were examined retrospectively in 62 infertile women who conceived multiple gestations with ovulation induction. The mean gestational age at birth of quadruplets was significantly less than that of twins reduced from quadruplets (24.8 versus 31.0 weeks; P less than .001), and there was appreciable neonatal mortality in the nonreduced quadruplets (62%). In twins selectively reduced from triplets as compared with nonreduced triplets, the mean gestational age at birth, though statistically significant, differed by an average of only 1.7 weeks (34.8 versus 33.1 weeks; P less than .05), and the mean gestational birth weight differed only by 380 g (2305 versus 1924.7 g; P less than .05). Triplets required a longer average stay in the neonatal intensive care unit than did twins resulting from multifetal triplet reduction (20.7 versus 8 days; P less than .001). Although five sets of triplets (20%) were born before 32 weeks, there were only two neonatal deaths, with the remainder of the 58 infants eventually discharged home. The mean gestational age of twins selectively reduced from triplets or quadruplets was significantly less than that for nonreduced twins (32.6 versus 35.3 weeks; P less than .001), and the groups differed by 1605 g in mean birth weight (1841.8 versus 2447.5 g; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1923194 TI - Umbilical cord blood gases and mortality and morbidity in the very low birth weight infant. AB - Umbilical cord blood gas values and morbidity and mortality were correlated in 191 very low birth weight (VLBW) infants (500-1500 g). The mean umbilical arterial pH and base excess differed significantly between survivors and non survivors. The presence of at least moderate acidosis (arterial pH 7.15 or lower) was related significantly to mortality, particularly in infants younger than 26 weeks. The mean cord blood gas values did not predict the presence or severity of hyaline membrane disease or intraventricular hemorrhage, but Apgar scores did. Bronchopulmonary dysplasia, neurologic sequelae, necrotizing enterocolitis, and sepsis also did not correlate with mean cord gas values, but neither did Apgar scores. Furthermore, the severity and type of acidosis did not relate to morbidity. Combining cord blood gases and Apgar scores did not help predict morbidity, which was not surprising because cord pH values correlated poorly with Apgar scores (all r values less than or equal to 0.26). We urge caution in interpreting cord gases as predictors of morbidity in the VLBW infant. PMID- 1923195 TI - Cord blood gas patterns identifying newborns at increased risk of group B streptococcal sepsis. AB - The effect of group B streptococcal sepsis acquired in utero on umbilical cord gas values is not known. Hypothesizing that fetal acid-base balance may be affected, we sought to identify a pattern of cord gas values that might detect newborns at increased risk of group B streptococcal sepsis. This review encompassed all newborns from January 1, 1986 to March 31, 1990 who manifested group B streptococcal sepsis as confirmed by a positive blood culture. An increased-risk cord gas profile was identified as an arterial pH less than 7.18 with either an arterial carbon dioxide pressure less than 59 mmHg or bicarbonate level less than 19 mEq/L. This pattern was found in four of 11 newborns with group B streptococcal disease but in only 43 of 4290 controls, yielding a relative risk of 51.7 (95% confidence interval 13.1-224.9). Our results suggest that a mild metabolic acidosis characterized by these indices may serve as an indicator of increased risk of early-onset group B streptococcal disease. PMID- 1923196 TI - Cord blood acid-base values in breech-presenting infants born vaginally. AB - The purposes of our investigation were to establish normal umbilical cord blood acid-base values for breech-presenting fetuses born vaginally and to compare our findings with values from cephalic-presenting fetuses delivered vaginally (control group). Our study population consisted of 30 term fetuses with frank breech presentation who fulfilled selective criteria for trial of labor and subsequently had uncomplicated vaginal breech deliveries. The mean (+/- SD) gestational age of the study group was 38 weeks, 5 days (+/- 1 week, 4 days); the mean birth weight was 3178 +/- 321 g and the median 1- and 5-minute Apgar scores were 7 (range 2-9) and 8 (range 7-9), respectively. Thirteen infants had assisted breech deliveries and 17 had assisted breech deliveries with forceps applied to the aftercoming head. We obtained umbilical arterial and venous blood samples for acid-base analysis from both the study and control infants. The results for the study group were: umbilical venous pH 7.32, PCO2 37.88 mmHg, PO2 22.88 mmHg, HCO3 25.92 mmol/L, and base deficit -4.90; umbilical arterial pH 7.23, PCO2 51.20 mmHg, PO2 18.85 mmHg, HCO3 19.42 mmol/L, and base deficit -5.86. Comparison of the subjects' umbilical cord blood acid-base values with those of controls demonstrated a statistically lower cord arterial pH (P = .0001) and a higher arterial PCO2 (P = .028). We conclude that umbilical cord arterial blood acid base values of the breech-presenting fetus born vaginally without complications differ from established normative umbilical cord blood gas values based on data obtained from uncomplicated cephalic-presenting fetuses delivered vaginally. PMID- 1923197 TI - Black-white differences in newborn anthropometric measurements. AB - The mean birth weight of black infants is consistently less than that of white infants. In 1518 low-income multiparous women, the mean difference in singleton births was 171 g, of which 38 g was partitioned to preterm births and another 35 g reflected lower gestational ages in term births. A series of regression analyses were used to determine the effect of black race on various newborn measurements in 1205 term newborns, adjusting for other known risk factors. In this model, black race accounted for a mean decrease of 148 g in weight and 0.52 cm in length. There were also significant decreases in mean head (0.44 cm), chest (0.66 cm), and abdominal (0.56 cm) circumferences. Arm and leg lengths were not different, but black arm circumferences (0.14 cm) were significantly larger. Triceps and thigh skin fold measurements were not statistically different, but black subscapular skin fold values were significantly smaller (0.17 mm). The ponderal index in blacks was significantly less than in whites. These data suggest that in this population, intrinsic and/or extrinsic factors associated with race account for most smaller black newborn measurements and for much of the racial difference in birth weight. PMID- 1923198 TI - A randomized comparison of assisted vaginal delivery by obstetric forceps and polyethylene vacuum cup. AB - The assisted vaginal delivery methods of rigid obstetric forceps and polyethylene vacuum cup extraction were compared in a prospective, randomized study. The 99 women studied had all completed 35 full weeks' gestation, required attempted assisted vaginal delivery, and were randomly assigned to either attempted forceps or vacuum-assisted delivery. All presentations were cephalic, with stations ranging from +1 to +4. Neonates were evaluated at 24 hours by neonatal staff. The infants underwent intracranial ultrasound screening during the first 24 hours of life and ophthalmologic examination within 48 hours. Vaginal delivery was successful with the intended method in 83% of vacuum-assisted deliveries and in 78% of forceps deliveries (not statistically significant). Neonatal retinal hemorrhage was found in 17 and 38% (P less than .043) of the randomized forceps and vacuum deliveries, respectively. No intraventricular hemorrhage was found. Apart from associations between vacuum-assisted delivery and mild hyperbilirubinemia and neonatal retinal hemorrhage (of uncertain clinical significance), and between assisted forceps delivery and an increased potential for facial injury, neonatal outcomes did not differ significantly. Maternal outcomes also did not differ significantly. No significant differences in safety or efficacy were found between polyethylene cup vacuum extraction and rigid obstetric forceps-assisted vaginal delivery in this population of predominantly low-pelvic assisted deliveries. Patients delivered by sequential use of forceps after vacuum or by vacuum after failed forceps application did not suffer significantly increased morbidity relative to those delivered by forceps or vacuum alone. Use of alternate or sequential methods allowed an overall cesarean rate of 3% in this population. PMID- 1923200 TI - Reliability of intrauterine pressure measurements. AB - The reliability of intrauterine pressure measurements was studied by placing two catheters in the same uterus in women in labor. Nineteen parturients were studied, five with two Intran I catheters in different pockets of amniotic fluid, five with two Intran II catheters in different pockets, and nine with two Intran II catheters in the same pocket of amniotic fluid. Among 1429 contractions studied, the catheters showed differences of pressure of less than 5 mmHg in 86% of contractions and of less than 10 mmHg in 94%. When cumulative uterine activity was calculated for each labor, the difference in the total active pressures shown by the two catheters was less than 5% in 17 cases and 5% or more in two cases. These differences are unlikely to be of any importance in the management of labor. PMID- 1923199 TI - Erythropoietin in preeclampsia. AB - To investigate the possible effect of preeclampsia on erythropoietin metabolism, we measured plasma and urine erythropoietin concentrations and complete blood count in 19 women with preeclampsia and nine healthy gravidas. Hemoglobin concentration and hematocrit values in the preeclamptic patients did not differ significantly from those of the normal pregnant controls. However, the plasma erythropoietin concentration tended to be higher in the preeclamptic group than in the normal pregnant controls (26.9 +/- 31.2 versus 11.2 +/- 9.9 mU/mL), though the difference was not statistically significant. Plasma erythropoietin concentration correlated negatively with both hemoglobin concentration and hematocrit (r = -0.85, P less than .01). The pattern and magnitude of the erythropoietin response to anemia paralleled that previously reported in individuals with iron deficiency anemia. No significant correlation was found between urinary erythropoietin excretion and blood pressure, qualitative albumin excretion, hematocrit, hemoglobin concentration, or plasma erythropoietin concentration. Based on our results, the erythropoietin response to anemia appears to be intact in preeclampsia, at least in the absence of renal failure. PMID- 1923201 TI - Vibroacoustic stimulation and intrauterine sound pressure levels. AB - The sound pressure level in amniotic fluid generated by vibroacoustic stimulation, assessed with a hydrophone placed close to the fetal head, was studied in 16 subjects. The mean recorded sound pressure level was 115 dB and the highest level was 129 dB. The range of the background noise was 63.5-80.5 dB. There was no obvious relationship between the distance from the stimulator to the hydrophone and the intrauterine sound pressure level. Although sound pressure levels are high, they are probably reduced before reaching the cochlea of the fetus because of the surrounding amniotic fluid and the fluid in the middle ear. PMID- 1923202 TI - Human fetal response to vibroacoustic stimulation as a function of stimulus duration. AB - The effect of stimulus duration on the initial fetal heart rate (FHR) acceleration response was evaluated by assessing its amplitude and span following a single vibroacoustic stimulation with durations of 0 (sham), 1, 3, or 5 seconds. Statistically significant differences were observed in the mean amplitude and duration of acceleration in groups 3 and 5 when compared with groups 0 and 1 (P less than .05). In addition, groups 3 and 5 demonstrated significantly greater fetal reactivity than group 0 and a decrease in testing time over groups 0 and 1 (P less than .05). Our results suggest that the magnitude of the FHR acceleration response is dependent on the duration of the stimulus. Furthermore, a 3-second sound stimulus appears to be adequate for a shift to the fetal behavioral "awake" state. PMID- 1923203 TI - Fetal and umbilical flow velocity waveforms between 10-16 weeks' gestation: a preliminary study. AB - Maximal flow velocity waveform recording was attempted in the umbilical artery, fetal descending aorta, and at the fetal intracerebral level using a cross sectional study design in 77 normal singleton pregnancies between 10-16 weeks' gestation. At 10-12 weeks, end-diastolic flow velocities were always absent in the fetal descending aorta and umbilical artery, but were present in 58% of the intracerebral artery waveforms. The pulsatility index at all three levels decreased significantly with advancing gestational age, suggesting a reduction in fetal and umbilical placental vascular resistance during the late first and early second trimesters of normal pregnancy. Waveform changes were not related to fetal heart rate. PMID- 1923205 TI - Sonographically homogeneous echogenic amniotic fluid in detecting meconium stained amniotic fluid. AB - A prospective study was performed to examine the hypothesis that sonographically homogeneous echogenic amniotic fluid (AF) may provide a marker for the presence of meconium-stained AF. Twenty term gestations in which homogeneous echogenic AF was demonstrated sonographically were compared with 40 cases with sonographically clear AF. Two cases in the study group had meconium-stained AF at delivery. All of the controls had clear fluid by amniocentesis (performed for lung maturation studies) immediately after the sonographic examination. Thus, homogeneous echogenic AF had a sensitivity of 100%, a specificity of 69%, a positive predictive value of 10%, and a negative predictive value of 100% in detecting meconium. We conclude that homogeneous echogenic AF does not necessarily detect meconium-stained AF. PMID- 1923204 TI - Fetal lateral ventricle choroid plexus cysts: the dilemma of amniocentesis. AB - Although lateral ventricle choroid plexus cysts in the second-trimester fetus have been considered a benign developmental phenomenon of no clinical significance, an association with trisomy 18 has been suggested. We designed a prospective study to determine whether karyotype analysis is indicated when such cysts are encountered on prenatal sonogram. During a 20-month period, 5400 low risk pregnant women were examined sonographically in the second trimester to evaluate the prevalence of fetal lateral ventricle choroid plexus cysts and the incidence of ultrasonographic anomalies associated with such cysts in fetuses with trisomy 18 referred from cytogenetic laboratories. Thirty cases of fetal lateral ventricle choroid plexus cysts (0.6%) were detected during the study period; 28 newborns were normal and two had trisomy 18. One of the affected infants had other associated ultrasonographic abnormalities suggesting aneuploidy, whereas no detectable abnormalities could be found in the other. Three other pregnant women were referred to us from the cytogenetics services because fetal karyotype revealed trisomy 18; in all three cases lateral ventricle choroid plexus cysts and other sonographic abnormalities were observed. In total, we scanned five fetuses with trisomy 18, of which all had lateral ventricle choroid plexus cysts and four had associated detectable anomalies. We could not find any association between cyst size, number, or laterality and trisomy 18. In addition to the five cases of trisomy 18 described, we found 33 other fetuses reported with trisomy 18 in the second trimester; of this total, 25 (66%) had lateral ventricle choroid plexus cysts and 30% had no other detectable abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1923206 TI - Anal sphincter competence in healthy women: clinical implications of age and other factors. AB - Normal variation in anal sphincter competence was examined with anal pressure profilometry, using a low compliant recording system and a perfused catheter, in 49 healthy women with a mean age of 51 years (range 20-79). Maximum resting anal pressure and maximum squeeze pressure declined with age (r = -0.61; P less than .001 for both), more rapidly so after menopause. Rectal pressure increased with body mass index (r = 0.60, P less than .001). Closing pressure (ie, the difference between maximum resting anal pressure and rectal pressure), an important determinant of anal continence, was more markedly reduced with age (r = -0.69, P less than .001) than was maximum resting anal pressure. Age-related changes were found for the length of the anal canal (r = -0.36, P less than .05). Parity and anal pressures were unrelated. Women are more frequently affected by anal incontinence than are men. Anal pressure profilometry is a useful diagnostic aid, though age-related changes must be taken into consideration when evaluating the results. The more rapid decline of anal pressures after menopause might imply that anal sphincter tissue is a target for estrogen. PMID- 1923207 TI - Comparison of Novak and Pipelle endometrial biopsy instruments. AB - A randomized study compared the Novak and Pipelle endometrial biopsy instruments with respect to quality of the biopsy obtained and pain related to the procedure. Fifty-five subjects were randomized to one of two groups. Twenty-six women had a biopsy using the Pipelle, followed immediately by one using the Novak instrument; 29 had the procedures performed in the reverse sequence. After the procedures, each woman completed a pain questionnaire. Individual histology slides were reviewed in a blinded fashion. The two biopsies from each subject were paired, and a reviewer indicated the preferred type of biopsy. The scores were analyzed by nonparametric tests. The instruments yielded biopsies of similar quality (z = 0.18, P = .856). Pain scores were lower for the Pipelle (z = -3.40, P = .001). The pathologist showed no preference when choosing Novak or Pipelle slides (chi 2 = 2.08, P = .149). In our patient population, the Pipelle instrument was comparable to the Novak instrument in obtaining adequate tissue and was significantly less painful. PMID- 1923208 TI - A randomized trial of three methods of obtaining Papanicolaou smears. AB - The relationship between technique of obtaining Papanicolaou smears, presence of endocervical cells, and rate of cervical neoplasia was studied by comparing an endocervical and ectocervical nylon brush (Bayne brush), Ayre spatula plus endocervical brush, and spatula plus cotton-tipped swab in a randomized, prospective trial involving 11,061 patients. Eligible patients had a cervix and were not pregnant. Clinic records of patients with abnormal cytology were reviewed to determine the pathologic diagnosis. Whether pathology was defined as including condyloma, dysplasia, and cancer; dysplasia and cancer; moderate dysplasia, severe dysplasia, and cancer; or just severe dysplasia and cancer, no significant difference was found in the rates of pathology between the three techniques. Endocervical cells were identified in 89.5% of smears obtained with the Bayne brush, in 91.5% with the spatula plus endocervical brush, and in 71.1% with the spatula plus cotton-tipped swab (P less than .001). Among smears obtained with the spatula plus swab, the rate of any pathology was higher in smears that contained endocervical cells than in smears in which endocervical cells were absent (2.0 versus 0.6%; P = .009). After correction for the influence of age, there remained predictive value with the presence of endocervical cells. Once corrected for the influence of age, the rate of pathology and abnormal cytology in smears obtained with the spatula plus brush or the Bayne brush was not dependent upon the presence of endocervical cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1923209 TI - Routine prothrombin time determination before elective gynecologic operations. AB - The prothrombin time (PT) test is routinely ordered to identify unsuspected bleeding disorders in patients before elective operations. We evaluated the usefulness of screening PT tests before elective gynecologic operations over a 6 month period at Women's Hospital in Los Angeles, California. Of 1546 patients, 1516 (98.1%) had normal test results. Charts of 25 of the 30 patients with abnormal values were available for review: 20 did not benefit from the test results, and five had indications for coagulation testing on history or physical examination. In the absence of specific indications, routine preoperative PT testing before elective gynecologic operations does not contribute to patient care and should be eliminated. PMID- 1923210 TI - Early evaluation of the urinary tract following radical hysterectomy: structure and function relationships. AB - One hundred ten consecutive patients with invasive gynecologic cancers, treated by radical hysterectomy at The University of California, Irvine Medical Center, underwent early postoperative intravenous pyelogram (IVP). An abnormal early postoperative IVP did not predict subsequent urinary tract dysfunction (anatomical defect or disrupted voiding pattern) at 3 months, which occurred in 29% of the patients, nor did it detect any unsuspected fistulas or ureteral obstruction that persisted beyond the 3-month follow-up. Urinary tract dysfunction was not significantly associated with tumor volume, operative blood loss, or the type of radical hysterectomy performed. However, the inability to remove a suprapubic catheter before the 21st postoperative day was associated with a significant increase in urinary tract dysfunction at 3 months (P less than .03). We conclude that, in the absence of intraoperative urinary tract injury or clinical symptoms suggesting fistula or ureteral obstruction, the routine use of postoperative IVP should be abandoned. PMID- 1923211 TI - Identification of epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor in surgically induced endometriosis in rats. AB - The present immunohistochemical studies used polyclonal antibodies specific to epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and monoclonal antibodies to the extracellular binding domain of EGF receptor to elucidate their presence and cellular distribution in surgically induced endometriosis in the rat. Uterine segments were implanted in the mesenteric region adjacent to a blood vessel for a period of 4-6 weeks. During operative reexploration, the implanted tissues were intact, morphologically similar to the controls, and consisted of a cyst containing clear fluid and associated adhesion formation. All the uterine cell types immunostained with antibody to EGF. The highest immunostaining intensity was associated with inflammatory cells infiltrated among endometrial stromal cells, followed by luminal and glandular epithelial and stromal cells. The cysts consisted of an inner simple columnar epithelium, surrounded by several layers of smooth muscle and connective tissue. The cyst epithelial layer immunostained weakly, while the supporting wall stained moderately. The inflammatory cells found within the cyst cavity immunostained very intensely, comparable to those in the endometrium. The patterns of immunostaining for TGF-alpha and EGF receptor were similar to that observed for EGF. Myometrial smooth-muscle cells and endothelial and smooth-muscle cells of arterioles were also immunostained for EGF, TGF-alpha, and EGF receptor, but with lower intensity than that of the endometrium. These observations suggest that, like normal uterine tissue, endometrial implants produce EGF and TGF-alpha locally and contain receptors for EGF. These results imply a possible paracrine or autocrine role for growth factors in the establishment and/or maintenance of endometriotic tissue. PMID- 1923212 TI - Court-ordered treatment in obstetrics: the ethical views and legal framework. AB - Four main ethical views have been put forward concerning court-ordered treatment of mentally competent pregnant women for fetal indications: 1) Such treatment is never justifiable; 2) it is justifiable provided it poses no health risks for the woman, minimally invades her bodily integrity, and would clearly prevent substantial harm to the fetus; 3) it is justifiable provided the maternal risks are low, there is a substantial likelihood that the fetus will suffer irrevocable harm without the intervention, and the treatment will likely be effective; and 4) it is justifiable provided the risks to the woman are ones she should reasonably accept, the fetal risks of treatment are minimal, and the potential fetal benefit is substantial. However, the first two views are too rigid to adequately handle the variety of clinical situations in which maternal treatment refusal can occur, and recent legal decisions have ruled out the other views. The ethics of court ordered treatment are often discussed as though the only interests involved are those of the pregnant woman and fetus, but other important interests may be relevant. An ethical view that avoids these difficulties and takes better account of the complexity of the issues is as follows: Such treatment is justifiable in rare, exceptional circumstances provided it poses insignificant or no health risks to the woman or would promote her interests in life or health and there are compelling reasons to override her autonomy. PMID- 1923213 TI - Quantifying clinical activity in a multi-site clerkship in obstetrics and gynecology. AB - Student evaluations of the obstetrics and gynecology clerkship at the University of Minnesota suggested dissatisfaction because of disparity in students' clinical participation among training sites. We therefore designed a method to evaluate student experience. We found that 19.6% of students completed all the clinical activities we designated as essential to an adequate clerkship experience. The average student on the clerkship completed 85.3% of the expected clinical activities. Clerkship sites varied widely (71.5-98.3%) as to the proportion of clinical activities completed by the students. Feedback from the students incorrectly implied that low clinical experience occurred in institutions served by private practitioners rather than full-time faculty. In reality, there was no difference in clinical activities accomplished with private physicians (84.2%) or with full-time faculty (86.6%). From later student evaluations, we concluded that measurement of clinical activities completed can serve as a stimulus to increase student participation. PMID- 1923214 TI - A quality-control program for colposcopic practice. AB - Quality control is accepted as an integral part of the cytology laboratory's activities. However, provision of similar safeguards for colposcopic practice in assessing patients with abnormal cervical cytology has been an elusive problem. This report describes the quality-control program for colposcopy that is used province-wide in British Columbia for 21 hospital-based clinics staffed by 35 colposcopists. Copies of the results of all colposcopic examinations performed are sent to the Central Cytology Laboratory where the program is coordinated and the data are collated, analyzed, and evaluated. These data are used to set standards against which each colposcopist's performance and activity can be measured. One of the quality-control indicators used is a comparison between the colposcopic impression of the lesion and the corresponding direct biopsy diagnosis. Correlation within one histologic degree occurred in 86% of patients examined; this information was used to set a performance standard of 80% as the quality-control index for this particular indicator. Three colposcopists had scores below this standard. Comparisons were also made between presenting cytology, directed biopsy results, initial colposcopic impression, and final colposcopic evaluation (the clinical working diagnosis). The other major aspect of the quality-control program consists of an analysis of all cases of diagnosed invasive cervical cancer in the province in a given year to determine whether any colposcopically related errors occurred in the investigation and management of these cases. This system helps to identify individuals who may benefit from additional training. PMID- 1923215 TI - Interrupted circular suture: bleeding control during cesarean delivery in placenta previa accreta. AB - Rapid accumulation of blood from the placental separation site during cesarean delivery for placenta previa obscures the surgical field and quickly leads to deterioration of the patient's vital signs. We used the following technique in eight cases of intractable bleeding among 49 cesareans for placenta previa. Following failure to control the bleeding by suture at the placental separation site via the lower segment cesarean incision, the vessels were ligated using interrupted 2-3-cm sutures at 1-cm intervals in a circle around the bleeding area on the serosal surface of the uterus. The sutures were placed as deeply as possible in order to reach the endometrium. This led to a marked decrease in bleeding and allowed the small vessels to be easily identified and ligated. The amount of blood transfused and the operation time were gradually reduced as we became adept in the use of this procedure. Our experience suggests that this technique could reduce the use of hysterectomy in cesarean for placenta previa. PMID- 1923216 TI - Modified posterior exenteration for ovarian cancer. AB - The operative description of a modified posterior exenteration along with operative findings, other operative procedures, postoperative course, and follow up information are presented for 47 patients (37 primary cytoreduction, ten secondary cytoreduction). All had stage IIIC or IV epithelial ovarian cancer with pelvic disease encasing the reproductive organs, pelvic peritoneum, cul-de-sac, and sigmoid colon. In addition to modified posterior exenteration, all patients had multiple other procedures performed as part of the cytoreductive efforts. Forty-five (95.7%) had optimal (less than 2 cm) cytoreduction and 18 (38.3%) had complete cytoreductive surgery. Thirty-four patients were ultimately rendered continent of feces (25 primarily and nine after colostomy reversal). Nine patients (19.1%) had serious morbidity and one (2.1%) died postoperatively. The median follow-up for those undergoing primary cytoreduction was 13.3 months (6 84). Nineteen (51.4%) were alive at the time of writing, 16 (43.2%) were dead, and two (5.4%) were lost to follow-up. Modified posterior exenteration effectively removes all visible pelvic disease with acceptable mortality. Hence, even patients with the most advanced cases of ovarian cancer may attain optimal cytoreduction and become ideal candidates for adjunctive therapy, with improved survival or a chance for cure. PMID- 1923217 TI - Notice of retraction. The impact of National Health Service Corps physicians in the lowering perinatal mortality rate in Dade County, Florida. PMID- 1923218 TI - Identification of Treponema pallidum in amniotic fluid and fetal blood from pregnancies complicated by congenital syphilis. AB - Two pregnant women with secondary syphilis underwent amniocentesis and evaluation for fetal syphilis. In both cases, motile spirochetes, typical of Treponema pallidum, were observed during dark-field microscopic examination of the amniotic fluid. The presence of T pallidum was confirmed by antitreponemal monoclonal antibody immunofluorescence assays and by rabbit infectivity tests using the amniotic fluid. In the first case, an infant at 35 weeks' gestation delivered within 24 hours of amniocentesis had hepatosplenomegaly, osteochondritis, and neurosyphilis. In the second case, a fetus at 24 weeks' gestation was hydropic and a fetal blood sample showed anemia, thrombocytopenia, and elevated liver enzymes. Fetal syphilis was confirmed by rabbit infectivity testing using fetal blood obtained by funipuncture. This is the first report of the diagnosis of fetal syphilis by funipuncture and confirmation of the presence of virulent T pallidum in the blood of a human fetus. The mother was treated for secondary syphilis, but the infant had residual signs of congenital infection at birth 14 weeks later. Neonatal serum from the first case and fetal serum from the second case showed specific immunoglobulin M reactivity with the 47-kd antigen of T pallidum by Western blot assays. A new wild-type strain of T pallidum, designated DAL-1, was isolated from the amniotic fluid of the first case and is available for future studies. We conclude that the presence of T pallidum in amniotic fluid or fetal blood indicates fetal-placental infection. Further investigation is necessary to determine the pathogenesis of amniotic fluid infection and its role in the prenatal diagnosis of congenital syphilis. PMID- 1923219 TI - An unusual constellation of sonographic findings associated with congenital syphilis. AB - Sonography of a fetus, later proved to have congenital syphilis, revealed hepatosplenomegaly, noncontinuous gastrointestinal tract obstruction, and placentomegaly. This unusual constellation of sonographic findings should raise suspicion of syphilis infection of the fetus. PMID- 1923220 TI - Severe fetal hydrops resulting from ABO incompatibility. AB - Severe fetal hydrops was diagnosed at 34 weeks' gestation. Funipuncture revealed a normal 46,XX karyotype and a hematocrit of 20%. Cesarean delivery was performed. Neonatal blood testing showed blood type B positive, positive direct and indirect Coombs, and an anti-B antibody titer of 1:64. The maternal blood group was O positive with a titer of 1:65,536 immunoglobulin G (IgG) anti-B antibody (after inactivation of IgM anti-B antibody). This report documents a rare case of fetal hydrops resulting from ABO incompatibility with neonatal survival. PMID- 1923221 TI - Severe nonimmune hydrops secondary to parvovirus B-19 infection: Spontaneous reversal in utero and survival of a term infant. AB - We present a case of intrauterine infection with parvovirus B-19 and accompanying severe nonimmune hydrops at 26 weeks' gestation. The fetus showed progressive recovery on ultrasound. A term infant was delivered with hepatosplenomegaly as the only abnormality. PMID- 1923222 TI - Prenatal ultrasound diagnosis of a fetal inguinal hernia containing small bowel. AB - A scrotal mass measuring 5.9 X 4.8 cm was identified during an ultrasound examination. The presence of intestine within the mass was suspected based on visualized peristaltic waves. After delivery, the diagnosis of an inguinal hernia containing small bowel was confirmed. To our knowledge, this case represents the first report of an inguinal hernia containing small bowel diagnosed by prenatal ultrasound. PMID- 1923223 TI - Crouzon syndrome: prenatal ultrasound diagnosis by binocular diameters. AB - This is a report of second-trimester prenatal diagnosis of Crouzon syndrome suggested by binocular and interorbital diameter measurement and family history. Early prenatal diagnosis provides the option of termination or optimal postnatal management for families who choose to continue the pregnancy. PMID- 1923224 TI - Transplacental passage of vancomycin during the second trimester of pregnancy. AB - Pharmacokinetics and drug monitoring of vancomycin were studied at mid-pregnancy in a patient with chorioamnionitis due to Streptococcus agalactiae. The terminal half-life remained in the normal range (4-6 hours) because of an equivalent increase in both volume of distribution and total plasma clearance. Transplacental passage of the drug was observed. Monitoring is mandatory for prolonged vancomycin therapy, and the results should be available within 24 hours. The therapeutic regimen of 15-20 mg/kg every 12 hours was sufficient for this patient's chorioamnionitis. Serum drug levels and renal function should be measured before increasing the vancomycin dosage. PMID- 1923225 TI - Indomethacin for preterm labor: fetal toxicity in a dizygotic twin gestation. AB - Indomethacin was given for the treatment of preterm labor in a twin pregnancy at a dosage of 200 mg/day for 7 days beginning at 34 weeks and 5 days' gestation. During treatment, one twin developed closure of the ductus arteriosus, tricuspid regurgitation, right ventricular dysfunction, and pericardial effusion. Severe oligohydramnios in both amniotic sacs appeared as well. All findings resolved within 7 days of discontinuation of the medication. The infants, delivered vaginally at 37 weeks' gestation, were alive and well at a 2-month follow-up visit. We believe that all fetuses of mothers treated with indomethacin should be closely monitored for early evidence of decreased amniotic fluid volume and constriction of the ductus arteriosus. PMID- 1923226 TI - Uterine-peritoneal amniotic fluid leakage: an unusual complication of intrauterine shunting. AB - Bilateral pleuroamniotic shunting was performed at 33 weeks' gestation in a fetus with bilateral hydrothorax, hydrops, and gross polyhydramnios. The procedure was successful, but acute amniotic fluid leakage into the maternal peritoneal cavity occurred soon after. This produced marked maternal discomfort and transient oligohydramnios, with consequent fetal distress. Expectant management was adopted in view of fetal lung immaturity. Resolution of maternal ascites occurred within 24 hours and the fetal heart rate normalized as amniotic fluid reaccumulated. The pregnancy progressed uneventfully thereafter. PMID- 1923227 TI - Pseudomonoamniotic twins with cord entanglement following genetic funipuncture. AB - Amniocentesis was performed twice on a twin gestation, and twice there was cell growth failure in one of the twins. Therefore, funipuncture was attempted at 24 weeks. The anatomical relationship and position of the fetuses, placental cord insertion, and membranous septum dictated needle entry into the cord of the lower left fetus through the sac of the upper right fetus and the septum. The procedure was uneventful and the pregnancy was carried to 39 weeks. However, the septum between the twins had been disrupted, creating a pseudomonoamniotic pregnancy. This was noticed only after delivery of the first fetus, when it was found that the two umbilical cords were entangled. We believe that, whenever possible, puncture of the membrane between twins should be avoided. Should puncture be necessary, the possibility of pseudomonoamniotic twins must be considered. PMID- 1923228 TI - Intrauterine pressure in acute iatrogenic hydramnios. AB - Amnioinfusion has become a common intrapartum procedure for the relief of cord compression. We report a case of acutely increased intrauterine pressure during amnioinfusion with maternal but not fetal distress. An important decrease in pressure and symptomatology occurred with withdrawal of only a small amount of fluid. Further study is needed of pressure-volume relationships in the uterus and effects on uteroplacental perfusion. Careful attention must be paid to infusion volumes and intrauterine pressure during amnioinfusion. PMID- 1923229 TI - Prolonged retention of intrauterine bones. AB - Two cases of prolonged intrauterine retention of fetal bones are presented to show that antecedent abortion may, though uncommonly, play a role in current gynecologic complaints. In these two cases, symptoms dated to antecedent abortions treated with D&C 13 years and 14 months before diagnosis, respectively. Complaints included secondary infertility, dysmenorrhea, and dysfunctional uterine bleeding. Hysteroscopy was necessary to make the correct diagnosis of retained fetal bones. In both cases, hysteroscopic surgery was unsuccessful in removing all the bony fragments or relieving symptoms. Though retained fetal bones are an uncommon cause of gynecologic problems, these cases show the necessity of hysteroscopy for diagnosis of persistent gynecologic problems when intrauterine pathology is suspect. These cases also demonstrate that although hysteroscopy is extremely useful diagnostically, it may not be successful therapeutically even for the persistent surgeon. PMID- 1923230 TI - Rubeola during pregnancy. AB - We report three cases of rubeola during pregnancy complicated by pneumonia. All had bacterial superinfection of the lungs and a clinically mild hepatitis. One woman delivered at term and two underwent successful tocolysis, one of whom had an unexplained stillbirth 7 weeks later. Rubeola virus is not a teratogen, although it has been associated with increased spontaneous abortion and perinatal mortality. PMID- 1923231 TI - Management of the pregnant patient with a cerebral venous angioma: a report of two cases. AB - Though there is a large body of knowledge regarding the management of pregnant women with arterial lesions in the central nervous system, little information is available on venous malformations. We report our experience with two pregnant patients with cerebral venous angiomas. These lesions are usually asymptomatic and only rarely cause seizures or subarachnoid hemorrhage. Based on our experience and literature review, we suggest that patients with venous angiomas without a history of hemorrhage can safely undergo labor and vaginal delivery. PMID- 1923232 TI - Pregnancy and delivery in a patient with Uhl anomaly. AB - We followed throughout pregnancy and delivery a 26-year-old woman suffering from a severe form of Uhl anomaly (congenital arrhythmogenic right ventricular dysplasia with severe enlargement and hypokinesis of the right ventricle, tricuspid valve insufficiency, and mild pulmonary valve insufficiency). Despite severely impaired cardiac function, the patient tolerated pregnancy surprisingly well. At 37.4 weeks' gestation, prophylactic low-dose heparin was started. Three days later she delivered a healthy 2700-g girl by elective cesarean performed under intensive cardiac surveillance. PMID- 1923233 TI - Use of intravenous amrinone in the short-term management of refractory heart failure in pregnancy. AB - The use of amrinone, a cardiac inotropic agent with vasodilatory properties, has not been described in human pregnancy. We report the use of amrinone in a woman at 18 weeks' gestation who had congestive heart failure secondary to bacterial endocarditis. Although her cardiac output and congestive heart failure improved, she developed hypoxemia, metabolic acidosis, and premature ventricular contractions. These effects resolved when the amrinone treatment was stopped. PMID- 1923234 TI - Life-threatening laryngeal edema in a pregnant woman previously treated for thyroid carcinoma. AB - A woman previously treated for papillary thyroid carcinoma developed life threatening laryngeal edema during each of two pregnancies. The second episode led to tracheostomy. The laryngeal edema probably resulted from immobilization of the vocal cord(s), possibly caused by the thyroid carcinoma treatment combined with upper respiratory infection and the general tendency toward edema during pregnancy. Patients with a narrow upper respiratory airway must be adequately monitored during pregnancy because prompt intervention may be needed. PMID- 1923235 TI - Transvaginal pressure pack for life-threatening pelvic hemorrhage secondary to placenta accreta. AB - A patient with placenta previa presented with severe vaginal bleeding. Emergency classical cesarean was followed by hysterectomy for placenta accreta. The patient's hemodynamic status continued to deteriorate and she subsequently developed a consumptive coagulopathy secondary to massive hemorrhage. A mushroom shaped pack, created from a sterile plastic bag filled with Kerlix gauze, was placed in the pelvis and brought out through the vagina. Traction on the pack produced pressure against the pelvic floor, controlling the bleeding. This pack was prepared quickly and removed without complication in the immediate postoperative period. PMID- 1923236 TI - Bromocriptine-associated headache: possible life-threatening sympathomimetic interaction. AB - We present two cases of severe headache associated with the use of bromocriptine for lactation suppression in otherwise healthy women. In each case, the additional use of a therapeutic sympathomimetic agent resulted in extreme worsening of symptoms with development of hypertension and life-threatening complications (ventricular tachycardia and cardiac dysfunction in one case, seizures and cerebral vasospasm in the other). Sympathomimetics in combination with bromocriptine in patients with a bromocriptine-associated headache during the puerperium may be dangerous. PMID- 1923237 TI - Recurrent anaphylaxis to a depot form of GnRH analogue. AB - Experience with depot forms of hormonal preparations suggests that severe adverse reactions are infrequent and immediate hypersensitivity reactions are rare. We report a case of recurrent anaphylaxis to a depot form of GnRH analogue requiring both acute and chronic management. PMID- 1923238 TI - Ovarian abscess arising within an endometrioma. AB - Ovarian abscess is a rare gynecologic entity; only 120 cases have been reported in the world literature. In contrast to the more commonly encountered tubo ovarian abscess, tubal involvement is absent in the ovarian abscess. This report describes a case of an ovarian abscess arising de novo within an endometrioma. The woman presented with a 20-cm pelvic-abdominal mass with paracaval adenopathy and bilateral ureteral obstruction. Treatment with broad-spectrum antibiotics was unsuccessful. The surgical specimen revealed endometrial glands, stroma, hemosiderin-laden macrophages, and evidence of abscess formation. PMID- 1923239 TI - Hemangioma of the cervix managed with the Nd:YAG laser. AB - A large hemangioma of the cervix was treated successfully with the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. A survey of the literature disclosed 39 cases of hemangioma of the cervix and vagina. Hysterectomy was the primary mode of therapy in 15 cases. More conservative approaches have been used in young women requesting preservation of their childbearing ability, including CO2 laser excision, knife excision, cryotherapy, and electrocauterization. In the case presented, the Nd:YAG laser was used in the non-contact mode for a photocoagulative effect. This technique results in destruction of the lesion with less danger of bleeding than with any other surgical technique. PMID- 1923240 TI - Vulvar reconstruction using a pedicle flap based on the superficial external pudendal artery. AB - We present a new method for vulvar reconstruction based on recently described vasculature of the lower abdominal skin and subcutaneous tissue. The superficial external pudendal artery supplies the region encompassing the suprapubic and infraumbilical skin. Thus, a pedicled skin flap based on the superficial external pudendal artery is designed in the suprapubic area and rotated into place for vulvar reconstruction. Because of the thickness and pliability of the flap as well as the inconspicuous donor scar, we believe this method of reconstruction to be superior to skin grafts or bulkier (ie, musculo- and fasciocutaneous) tissue flaps. PMID- 1923241 TI - Dysplastic vulvar nevi. AB - Of several pigmented vulvar lesions, the dysplastic nevus, a know precursor of malignant melanoma, has been described only twice. Focusing on pigmented vulvar lesions, 18 were excised among approximately 500 unselected parturients. Three lesions showed clinical and histologic characteristics of a dysplastic nevus. The patients with a dysplastic vulvar nevus were 21, 27, and 30 years old, respectively; all three had multiple torso and limb nevi and two had anamnestic features of the dysplastic nevus syndrome. Only one was aware of her vulvar lesion. All dysplastic nevi were brown or black and were larger than 5 mm in diameter. Our cases suggest that dysplastic vulvar nevi may be more frequent than previously thought. We suggest that the puerperium is a suitable time for a definite histologic diagnosis of large-size lesions with variegated pigmentary patterns and irregular borders that occur on the vulvar skin. Likewise, in other patients with suspected dysplastic vulvar nevi, excisional biopsy is recommended. PMID- 1923242 TI - Acute urethral obstruction due to condylomata acuminata. AB - Urethral obstruction is a rare disease in women, and even more uncommon is the occurrence of acute urethral obstruction due to condylomata. This case report describes the course of one such case, unique for its progressive clinical evolution, the primary involvement of the lower urinary tract in the absence of either an obvious primary site or a history of sexual intercourse for more than 15 years, and its successful treatment with cryotherapy. PMID- 1923243 TI - Vaginal fibromyomata: two cases with preoperative assessment, resection, and reconstruction. AB - Vaginal fibromyomata are rare benign neoplasms; approximately 300 have been reported in the world literature. The clinical presentation is variable and the consistency of the mass on pelvic examination may be misleading. A mass may occur anywhere along the vaginal tube and is usually localized, mobile, nontender, and circumscribed. Its consistency, however, may range from solid to cystic. These lesions may be asymptomatic or may cause pain or urinary tract symptoms. Transabdominal and intravaginal sonography along with needle biopsy are valuable in making the preoperative diagnosis of a benign smooth-muscle tumor. Vaginal enucleation is the treatment of choice. Operative management should include evaluation of urethrovesical support and possible reconstruction, eg, pubourethral ligament plication. PMID- 1923244 TI - Distinguishing tubal metaplasia from endocervical dysplasia on cervical Papanicolaou smears. AB - Tubal metaplasia is a benign endocervical lesion. There may be confusion, however, in distinguishing tubal metaplasia from endocervical gland dysplasia on Papanicolaou smear. We present a case in which a cervical smear diagnosis initially reported as endocervical atypia was corrected to a diagnosis of tubal metaplasia upon cytologic review, thus altering patient management. The presence of terminal bars and cilia are the most helpful features in the cytologic recognition of tubal metaplasia. The evaluation of endocervical gland dysplasia suggested by Papanicolaou smear may include diagnostic conization; therefore, to prevent unnecessary intervention, it is important to distinguish endocervical gland dysplasia from tubal metaplasia. PMID- 1923245 TI - Peritoneal sarcoidosis and elevated CA 125. AB - Although CA 125 is generally considered a serum marker of malignant tumors, it may be elevated in conditions characterized by peritoneal inflammation. We report a patient with known pulmonary sarcoidosis who presented with an adnexal mass and an elevated CA 125. At laparotomy, she was found to have miliary peritoneal disease simulating the appearance of metastatic cancer. Microscopic examination revealed a benign ovarian cyst and diffuse granulomatous disease similar to that present in the lung. PMID- 1923246 TI - Sarcoid-like lesions associated with epithelial ovarian adenocarcinoma. AB - A woman with poorly differentiated endometrioid adenocarcinoma of the ovary had sarcoid-like lesions in the bone marrow. Sarcoid-like lesions may be misinterpreted as metastatic disease, resulting in inappropriate modification of therapy. PMID- 1923247 TI - Papillary serous carcinoma of the peritoneum following endometrial cancer. AB - Two cases of advanced papillary serous carcinoma of the peritoneum occurred after hysterectomy and bilateral salpingo-oophorectomy for endometrial carcinoma. Careful resectioning of the original ovarian specimens failed to demonstrate a previously undiagnosed ovarian malignancy. In both cases, CA 125 levels, which were being followed routinely because of the previous endometrial cancer, rose before the diagnosis of peritoneal carcinoma and corresponded closely to patient response to therapy. PMID- 1923248 TI - Vaginal laceration following a jet-ski accident. AB - A 17-year-old woman riding as a passenger on a jet-ski fell behind the jet nozzle while jumping waves. A vaginal laceration with intra-abdominal extension occurred as a result of the accident. Hypogastric artery ligation controlled the hemorrhage and avoided more extensive surgery. The case represents an unusual injury from this type of watercraft and illustrates important points in the management of genital tract trauma. PMID- 1923249 TI - Prolonged retention of laminaria fragments: an unusual complication of laminaria usage. AB - A single laminaria japonica was placed the day before an abortion requested by a 32-year-old nulliparous woman. On the day of the procedure, the laminaria was found to be tightly wedged in the cervix, and attempts at removal resulted in pushing the laminaria into the uterine cavity. The abortion was completed, and 3 days later, after placement of additional osmotic dilators, the intrauterine laminaria was crushed and removed. Fifteen months later, a small fragment of laminaria passed spontaneously. Hysteroscopy was performed, and approximately 30 fragments of laminaria were removed. PMID- 1923250 TI - Ectopic pregnancy. PMID- 1923251 TI - Epidemiology and etiology of ectopic pregnancy. AB - Although advances in earlier diagnosis have led to decreased case-fatality rates and conservative laparoscopic treatments have enabled improved outcomes, ectopic pregnancy remains a leading cause of maternal mortality and accounts for a sizable proportion of infertility and ectopic recurrence. The incidence of ectopic pregnancy, the trends observed in the last decade, reason for occurrence, and other questions regarding risk factors for this condition are discussed. PMID- 1923252 TI - Salpingectomy. AB - Salpingectomy remains the standard surgical treatment of ectopic pregnancy. The mode of access--laparotomy versus laparoscopy--should not influence the choice of treatment. The determining factors in the choice of surgical treatment of tubal pregnancy are the patient's vital signs, desire for future fertility, age, previous history of infertility and tubal status, and the availability of and accessibility to assisted reproductive technology. The technique of salpingectomy consists of complete removal of the fallopian tube, including the proximal isthmus but not the interstitial portion. Care must be taken not to damage the vascular supply of the ovary. PMID- 1923253 TI - Expectant management of ectopic pregnancy. AB - Figure 2 outlines the management protocol used at the University of Tennessee. Expectant management either in the presence or absence of tubal abortion offers an alternative to surgical management of ectopic pregnancy. With proper patient selection and follow-up, surgery can be avoided in a significant number of patients who once would have required operative intervention. PMID- 1923254 TI - Repeated ectopic pregnancy. AB - The literature concerning ectopic pregnancy is reviewed with regard to the information on multiple ectopic pregnancies. The epidemiology, causes, and treatments for multiple ectopic pregnancies are summarized. In addition, the results of radical and conservative surgical management procedures and medical management are discussed in the context of the fertility of patients with multiple ectopic pregnancies, and procedures appropriate for the infertile patient are discussed. PMID- 1923255 TI - Persistent ectopic pregnancy. AB - The potential hazards of persistent ectopic pregnancy are becoming more relevant as the incidence of ectopics increases and surgical treatment continues to evolve from a radical to a conservative approach. As a complication following conservative surgery, the incidence and possible management strategies of early detection and treatment of persistent ectopic pregnancy are discussed. PMID- 1923256 TI - New techniques in the diagnosis of ectopic pregnancy. AB - Pulse and color Doppler studies have provided a potent method for the investigation of functional changes and pathologic conditions in the female pelvis, both in the gravid and nongravid state. Combined with transvaginal sonography, which optimizes the imaging capability, the transvaginal color Doppler ultrasonography provides a new major modality for reproductive flow studies that have hitherto been possible only in animal models because of the invasiveness of the technique. Apart from these potential applications of the technique for research purposes, however, transvaginal imaging and the Doppler technique have become major modalities in all patients suspected of ectopic pregnancy at our institution. PMID- 1923257 TI - Tubal pregnancy. Associated histopathology. AB - Endometrial histologic characteristics are of little value in predicting ectopic pregnancy. The growing tubal gestation does not have any unique characteristics as far as the maternal-fetal tissue interface is concerned. The placentation is relatively superficial, and the growth is intraluminal. Tubal rupture occurs as a result of progressive tubal distention with focal hemorrhagic necrosis. Persistence is a reflection of incomplete evacuation combined with the noncyclic shedding of the tubal epithelium. The evacuated implantation site and conservative surgical incisions are not directly related to the recurrence of ipsilateral tubal pregnancies. The most common histologic finding related to tubal pregnancy is that of prior tubal disease. PMID- 1923258 TI - Linear salpingostomy for ectopic pregnancy. AB - Linear salpingostomy is the procedure of choice for management of uncomplicated ectopic gestations if certain constraints are met. The procedure is straightforward and may be performed by laparotomy. However, laparoscopic salpingostomy is becoming the preferred approach. Additionally, laparoscopy decreased operative time, hospital stay, and patient recovery time. Postoperatively, patients should be observed with weekly assessment of beta-hCG titers to ensure complete resorption of any viable trophoblast. Failure of resorption may result in a persistent ectopic pregnancy. Reproductive outcome is preserved in most patients, with intra-uterine pregnancy rates that approach 60%. Recurrent ectopic gestation rates of 15% are acceptable in view of subsequent close surveillance in women who have undergone previous salpingostomies, which also facilitates earlier diagnosis. PMID- 1923259 TI - Learning how to communicate with patients. PMID- 1923261 TI - Economic credentialing--and what you can do about it. PMID- 1923260 TI - Patient transfer laws amended. PMID- 1923262 TI - Will Ohio physicians be mandated to reveal HIV-positive tests? PMID- 1923263 TI - OSMA's AIDS proposals. PMID- 1923264 TI - House considers Medicaid assessment. PMID- 1923265 TI - Medicare picks Cleveland for its controversial cataract plan. PMID- 1923266 TI - Medicare fee schedule holds bad news for most physicians. PMID- 1923267 TI - Reynolds' illness and autopsy. The ill-sighted portrait painter. PMID- 1923268 TI - Prescription precautions. Avoid the pitfalls and reduce liability. PMID- 1923269 TI - Forensic dentistry. PMID- 1923270 TI - Bite marks and cans--child abuse and neglect syndrome. PMID- 1923271 TI - Dear associate: open letter to those thinking of starting their own practice. The first of a three part series. PMID- 1923272 TI - Becoming an associate. Seeing is believing. The second of a three part series. PMID- 1923273 TI - What do you want to be when you grow up? PMID- 1923275 TI - Your community health dentist. An ally in oral disease prevention. PMID- 1923274 TI - Toothbrush design and effectiveness. Findings from a study of dental offices. PMID- 1923276 TI - Public health dentistry in Ontario. PMID- 1923277 TI - Buying a practice. Seeing is believing. The third of a three part series. PMID- 1923278 TI - Life insurance. Two forgotten needs. PMID- 1923279 TI - Computers in the dental office. A look at the pros and cons of computerization. PMID- 1923280 TI - Bleaching techniques. PMID- 1923281 TI - Retirement planning. How to protect yourself against inflation during retirement. PMID- 1923283 TI - Human resources management--a challenge for the nineties. PMID- 1923282 TI - Dental implants. A cosmetic solution for the severely atrophied edentulous jaw. PMID- 1923284 TI - Preparing your will. How to choose an executor. PMID- 1923285 TI - Dentistry and practice management. Some words of caution. PMID- 1923286 TI - [The possibility of lens formation in explants of the retina and pigment epithelium of the eye in chick embryos]. AB - Undissociated tissue explants of the retina and retinal pigment epithelium (RPE) of 3,5-, 4-, 5- and 8-day-old chick embryos were cultured in vitro. After 7 days in culture, lentoids were observed in explants of either retina or RPE from 3,5-, 4- and 5-day-old embryos. As demonstrated by immunohistochemistry, these lentoids contained specific chick lens proteins (alpha-, beta- and delta-crystallins). No crystallin-containing cells were found in eye tissue explants from 8-day-old embryos. However, when 5-bromo-deoxyuridine (25 microM) was introduced into the medium at the beginning of culturing (for 12 h), large eosinophilic cells containing alpha-, beta- and delta-crystallins were detected in retinal explants of the 8-day old embryos. Thus, retina and RPE of 3,5-5-day-old chick embryos are capable of lens differentiation after explantation in vitro without dissociation into individual cells. This capacity is lost during development. PMID- 1923287 TI - [Erythroblast antigen expression in murine hematopoietic and nonhematopoietic cells. 2. An immunofluorescent study in pre- and postnatal ontogeny using monoclonal antibodies]. AB - The expression of erythroblast antigen (Ag-Eb) in cell membranes during pre- and postnatal mouse development was studied by immunofluorescence using the monoclonal antibody MAE-15. Ag-Eb was detected in embryonic liver, spleen, epithelia of intestine, various glands and skin, as well as in extraembryonic tissues (yolk sac and trophoblast). In pregnant mice positive immunofluorescence was observed in placenta and on the surface of decidual cells in uterus. In adult non-pregnant mice Ag-Eb expression was detected not only in membranes of erythroid cells, but also in non-hemopoietic tissues, such as epithelia of various glands, intestine, kidney and testis, brain endothelium, basal layer of epidermis, and intercalated discs of the heart muscle. A possible role of Ag-Eb in processes of cell transport is discussed. PMID- 1923288 TI - [Congenital forms of brachydactyly and dermatoglyphics]. AB - Relative length and ridge count in dermatoglyphs of patients with various forms of brachydactyly were compared to those of the corresponding controls. In most cases of brachydactyly, fingers shortening was associated with the decreased ridge count, and only in two patients with brachydactyly D this relationship wasn't detected. It appears that brachydactyly may be due either to the abnormal positional information or disturbed function of certain growth factors responsible for the expression of inborn growth potential. PMID- 1923289 TI - [An immunochemical study of the interaction of human trophoblastic beta glycoprotein with steroid and sex hormones]. AB - Human trophoblastic beta-glycoprotein (TBG) was subjected to immunoelectrophoresis with intermediate gel containing hormones. We have observed TBG binding either with cyclopentaneperhydrophenanthrene derivatives (cholesterol, testosterone, progesterone, estradiol, estrone) or their synthetic analogs (sinestrol, diethylstilbestrol). TGB showed markedly higher affinity to estrogens than to other hormones. PMID- 1923290 TI - [The effect of inflammation on splenic colony formation after the intraperitoneal administration of bone marrow cells]. AB - The number of spleen colonies formed after intraperitoneal injection of bone marrow cells increases approximately 100-fold in mice with inflammation induced by nitrocellulose filters implanted into the intraperitoneal cavity. By transplanting these filters together with cells grown on them into intact animals and replacing them with clean filters we have demonstrated that this effect is associated with inflammation focus in the peritoneal cavity rather than with CFU S proliferation of the filter surface. PMID- 1923291 TI - [The discussion by A. I. Zotin and A. A. Neifakh in the journal Ontogenez]. PMID- 1923292 TI - Quality of life and cataracts. PMID- 1923293 TI - Quality of life and cataracts: a review of patient-centered studies of cataract surgery outcomes. AB - In the next 10 years growing numbers of adults will be reaching the age at which senile cataracts typically develop. At the same time, pressure is strong to contain medical expenses. In order to formulate wise public policy in this area it is important to describe the effects of this treatment on the patient's quality of life. After a general discussion of research on patient-centered medical outcomes, 18 studies of patient-centered cataract surgery outcomes are reviewed. Then the findings, both direct outcomes (visual acuity, percentage visual impairment, complications, visual functioning, physical and mental functioning, general well-being, and satisfaction with care) as well as modifying factors (type of prosthesis, presurgical functional status, condition of fellow eye, other ocular pathology, comorbidity, age, gender, socioeconomic status, attitudes, and values) are summarized. The closing discussion summarizes findings, describes two studies underway, and suggests directions for future studies of cataract surgery effects. PMID- 1923294 TI - Removal of lens epithelial cells by dispersion with enzymatic treatment followed by aspiration. AB - We conducted a preliminary trial of a method of lens epithelial cell removal in cataract surgery that combined mechanical and pharmaceutical treatments. The cells were first loosened from their junctional complexes with Dispase, a preparation of a neutral protease used for separating cells in tissue culture. To avoid intraocular tissue damage, the enzyme preparation was dissolved in sodium hyaluronate and injected into the capsular bag, which was carefully preserved during endocapsular cataract surgery. The cells were then removed by irrigation and aspiration. The results of experiments in vitro and in rabbits and, judging from the histopathologic examination, with negligible damage to the zonules or corneal endothelium. PMID- 1923295 TI - The use of 5-fluorouracil in patients following combined trabeculectomy and cataract extraction. AB - We studied the effect of postoperative administration of subconjunctival 5 fluorouracil in maintaining postoperative filtration following combined trabeculectomy and extracapsular cataract extraction with posterior chamber lens implantation. Three months postoperatively, the mean intraocular pressure in 15 patients who had received 5-fluorouracil was 13.1 +/- 3.2 mm Hg; in 17 control patients, it was 13.0 +/- 3.0 mm Hg (P greater than .05). The mean number of postoperative medicines in the study patients was 0.7; in the control patients, 0.8 (P greater than .05). Bleb appearance and improvement in visual acuity were similar in the two groups. This study does not support the routine use of 5 fluorouracil in patients who have undergone combined trabeculectomy and extracapsular cataract extraction. PMID- 1923296 TI - The keratoprosthesis: improved biocompatibility through design and surface modification. AB - Due to poor biocompatibility, the success of keratoprostheses has been limited. We compared a newly-designed PMMA intracorneal keratoprosthesis, covalently coated with type-I collagen, with an identical, uncoated keratoprosthesis were retained for 15 months, the uncoated implants had more extensive adjacent corneal melting, greater inflammatory response, and more epithelial downgrowth than their collagen-coated counterparts. Electron microscopy showed that stromal collagen fibers had attached to the surface of the coated implants, but not to that of the uncoated ones. Intracorneal keratoprostheses covalently coated with type-I collagen may offer superior biocompatibility and become significantly incorporated into corneal tissues. PMID- 1923298 TI - Cataract extraction in a patient with carotid cavernous sinus fistula. PMID- 1923297 TI - Modified Tessier flap for reconstruction of the upper eyelid. AB - We present a modification of the Tessier or orbitonasojugal flap for use in upper eyelid reconstruction. It is suitable for repairing full-thickness defects involving 60% or more of the lid margin and has the advantage of being a one-step procedure. PMID- 1923299 TI - Canaliculectomy in the treatment of keratitis sicca. AB - In patients with keratitis sicca (exposure keratopathy) in whom treatment with topical tear solutions and ointments is not effective, closure of the lacrimal puncta is performed with insertion of plugs or by cautery, hypercation, or laser. If punctal occlusion fails with these modalities, surgical excision of the canaliculi is recommended. Canaliculectomy successfully relieved ocular irritation and keratopathy in three patients with keratitis sicca, with no complications (follow-up, 10 to 26 months). PMID- 1923300 TI - Outpatient dacryocystorhinostomy. PMID- 1923301 TI - Postoperative instructions for cataract patients. PMID- 1923302 TI - Internal gas tamponade for retinal detachment with inferior fishmouthing. PMID- 1923303 TI - [Changes in postoperative corneal astigmatism after laser dissection of corneo scleral sutures]. AB - In a group of 68 consecutive cases of high surgically induced corneal astigmatism following extracapsular cataract extraction or phacoemulsification, single limbal sutures were released by argon laser. Visual acuity and refractive results 2-6 weeks after treatment were compared to those before laser application. The effect of suture dissection was analyzed according to the number of sutures released, the follow-up time from cataract surgery and previous corneal astigmatism. The effect of suture dissection was not dependent on the interval from surgery up to 20 weeks postoperatively. The reduction in astigmatism amounts 2.25 dptr up to 8 weeks, occasionally 2.5 dptr 8-10 and 11-16 weeks after surgery, and 1.75 dptr up to 20 weeks thereafter (mean values). The longer the interval the more sutures had to be released. If only one suture was dissected, the reduction in astigmatism amounted 1.75 dptr (mean), if two sutures were released the effect was 2.5 dptr, three or more dissected sutures lead to a 3.4-dptr reduction in corneal astigmatism. The axis of astigmatism did not change in 52 of 59 cases, but in some subjects oblique astigmatism appeared after suture dissection. PMID- 1923304 TI - Foster Kennedy syndrome and optociliary shunt vessels in a patient with an olfactory groove meningioma. AB - A 48-year-old woman complained of acute loss of vision in her right eye. Ophthalmoscopically, the right optic disk appeared pale, and abnormally dilated vessels were noted on the disk. The left optic disk was reddish and swollen. Fluorescein angiography revealed abnormal vessels on the right optic disk that might be venous. The patient had right-sided anosmia. Computed tomography and magnetic resonance imaging showed a lesion in the frontal lobe that was deviated to the right and attached to the olfactory groove. A histopathologic study of the excised specimen disclosed a meningioma. We believe that this patient with olfactory groove meningioma represents a rare case of Foster Kennedy syndrome and optociliary shunt vessels. PMID- 1923305 TI - A case of Parinaud's syndrome in a boy with delayed puberty. AB - The authors describe a case of Parinaud's syndrome in a 14-year-old boy with delayed puberty. The neurological examination and the neuroradiological work-up excluded the presence of cerebral pathological processes except for a pituitary microadenoma. As the sole presence of the microadenoma cannot justify gonadotropin deficiency, the authors in this case favor a form of isolated gonadotropin deficiency, and they suggest that the elevation paralysis can be put in the range of median line defects, such as labiopalatoschisis and hypoplasia of the olfactory bulbs, frequently associated with isolated hypogonadotropic hypogonadism. PMID- 1923306 TI - Recurrent mixed tumor of the right lacrimal gland causes acute contralateral visual loss. AB - A 23-year-old woman underwent excisional biopsy of a right palpebral mass: the histopathologic study showed a benign mixed tumor of the lacrimal gland. Thereafter, the tumor recurred repeatedly, and multiple excisions were done. Subsequently, right orbital exenteration was performed, and some orbital and frontal bones were removed. When the patient was 52 years old, the orbital tumor recurred. A histopathologic study revealed malignant transformation. At the age of 54 years, the patient suffered acute loss of vision in her left eye. Computed tomography disclosed invasion of the tumor into the posterior paranasal sinuses and brain. PMID- 1923307 TI - Low-vision aids in Stargardt's disease. AB - The use of low-vision-aids (LVAs) to improve distance and near visual acuity was evaluated in 27 patients. Most of the patients had a useful distance vision with or without glasses, and 24 patients (89%) were prescribed a near visual aid successfully. The high success rate was attributed to young age, strong motivation and myopic refractive error of these patients. We recommend the trial of LVAs to patients with Stargardt's disease who have visual difficulties. PMID- 1923308 TI - Colour vision testing in pre-school-aged children. AB - 84 children aged from 2 to 6 years were tested with three different pseudo isochromatic plates: Velhagen Pflugertrident test, Lanthony Tritan Album and Ishihara test. The Velhagen test was correctly interpreted by all of the 6- and 5 year olds, by 80% of the 4-year olds and by 20% of the 3-year olds. The Lanthony Tritan Album was well performed by all of the 6-, 5- and 4-year olds, and by 80% of the 3-year olds. The Ishihara test was acceptably performed by all of the 6- and 5-year olds, by 90% of the 4-year olds and by 40% of the 3-year olds. None of the 2-year olds could understand any of these tests. In the Ishihara test, the winding lines in the plates No. 30 and 32 were difficult for children; the incomplete interpreting of them must be accepted for a correct answer. PMID- 1923309 TI - Ocular findings in X-linked ichthyosis: a survey on 38 cases. AB - The authors report on the occurrence of ocular abnormalities in X-linked ichthyosis (XLI) patients, in their carrier mothers and in healthy volunteers who served as controls. The diagnosis of XLI was based on: (1) demonstration of steroid sulfatase deficiency in cultured skin fibroblasts; (2) lack of hybridization of patient's deoxyribonucleic acid (DNA) with specific steroid sulfatase complementary DNA probe; (3) electrophoretic mobility of plasma lipoproteins. Cholesterol sulfate plasma levels were also determined. The incidence of corneal opacities was the same in XLI patients and in their carrier mothers (23.7 and 24.3%, respectively). Neither other corneal nor ophthalmological alterations were found. Moreover, in XLI patients the plasma levels of cholesterol sulfate were about twenty times higher than in controls. Our findings demonstrate that ocular changes do not seem to be an absolute criterion for a definite diagnosis of XLI and the fact that the pathogenesis of corneal opacities is not due to an accumulation of cholesterol sulfate, but rather that this compound probably induces physicochemical changes of the corneal tissue properties. PMID- 1923310 TI - Cytological evaluation of adenoviral follicular conjunctivitis by cytobrush. AB - Conjunctival brush samples from 38 patients with acute conjunctivitis were examined to determine whether cellular features could be utilized for cytodiagnosis. Of all cases, 32 (84%) patients showed a characteristic cell pattern for adenoviral follicular conjunctivitis (AFC) and in the remaining 6 (16%) patients herpetic infection was suggested cytologically. The background of the conjunctival smears from patients with AFC was characterized by the predominance of lymphocytes with little fibrinous discharge. In addition, two types of nuclear alterations were demonstrated i.e. intranuclear inclusions and a so-called ground-glass nuclear appearance. Ground-glass nuclei occurred more frequently than intranuclear inclusions in patients with AFC. However, the presence of lymphocytes in conjunctival smears was a useful criterion for making the differential diagnosis between herpetic and adenoviral infections. Thus, in the absence of these three cellular changes, i.e. ground-glass nuclei, intranuclear inclusions and lymphocytic background, infectious conditions other than AFC may be considered, regardless of the numbers of conjunctival cells present. Emphasis is placed on the value of conjunctival brush cytology for the rapid diagnosis of cases of suspected AFC. PMID- 1923311 TI - Extracellular materials in the endothelial meshwork of organcultured human trabecular meshwork. Morphologic and morphometric study. AB - Twenty-three normal cadaver eyes were used in this study. Eight trabecular meshwork explants were dissected at 45-degree intervals from a 77-year-old donor eye and cultured for 2 weeks for studying circumferential differences in the amount of extracellular materials in the endothelial meshwork. One trabecular meshwork explant was dissected from each of 22 individual eyes (age range: 64-89 years) and cultured for 2 weeks to study the effect of age on the amount of the extracellular materials. Then, 5 consecutive electron micrographs in the endothelial meshwork were obtained from the individual specimens and subjected to morphometric studies. In the endothelial meshwork, the results revealed: (1) no statistically significant circumferential differences in the amount of extracellular materials and (2) no statistically significant changes associated with aging in the amount of these materials. PMID- 1923312 TI - Retrobulbar cysts in Aicardi's syndrome. AB - Case report of a four-year-old girl with Aicardi's syndrome diagnosed from the triad: absence of the corpus callosum, focal seizures, and chorioretinal lacunae. In addition, MR scans and orbital ultrasonography detected retrobulbar cysts behind the right microphthalmic eye not described so far. Analyzing the histological data from two previous reports, it becomes likely that the cysts have formed from abnormal migration of neuroretinal tissue through the border of the optic disc coloboma that was also present. This pathomechanism is also known in isolated colobomatous microphthalmos in which cysts may occur. PMID- 1923313 TI - Central pulverulent (Coppock) cataracts. A sibship of two Arab females with full cousin normal parents. AB - Two Arab (Saudi) sisters are described each with bilateral typical central pulverulent (powdery) or Coppock cataracts. As their unaffected parents are first cousins, the heredity is probably autosomal recessive, unlike the autosomal dominant heredity of the vast majority of previously described cases in the literature. Chromosomes were normal in all four individuals. There are no other children in the family. Both children and both parents were phenotypically Fy a - b+, reasonably common in Arab populations, so that any linkage to the Duffy blood group is neither supported nor refuted. PMID- 1923314 TI - An update on microphthalmos and coloboma. A brief survey of genetic disorders with microphthalmos and coloboma. AB - This is a brief survey of more than 100 syndromes in which microphthalmos and/or coloboma appear. It is suggested that the disorders be assessed systematically by consecutive discussions of their aetiology, morphology and embryology. PMID- 1923315 TI - The use of diagnostic registers. AB - This paper describes the structure and function of a number of diagnostic indexes used in the Genetic Clinic at Moorfields Eye Hospital. The disorders for which separate diagnostic indexes have been compiled are retinitis pigmentosa, retinoblastoma, and congenital glaucoma. PMID- 1923316 TI - Italian register for retinoblastoma. Pros and cons of a retrospective statistical study. AB - In an attempt to verify some of the current conflicting results concerning the impact of relevant prognostic factors in the retinoblastoma therapy, the authors took into consideration, for statistical analysis, the series of 459 cases included in the Italian Registry for retrospective study of retinoblastoma. Although this series appears large enough, problems related to the continuously changing approaches to the disease and the consequent lack of standardization often make it difficult to draw significant conclusions. Hence, while historical (retrospective) analysis often allows the manipulation of a great number of data, particularly in the case of relatively rare diseases, prospective randomized controlled trials are strongly recommended to standardize definitely the relevant prognostic criteria. These and other problems related to retrospective analysis are discussed in detail. PMID- 1923317 TI - Recurrent and new tumours during conservative treatment of bilateral retinoblastoma. AB - Conservative treatment of retinoblastoma is a combination of different therapeutic modalities: radiotherapy, photocoagulation, cryocoagulation, chemotherapy. The choice of the most suitable treatment depends on the stage of the disease. The evaluation of the regression and quiescence of tumoral foci after radiotherapy, Xenon photocoagulation or cryocoagulation is based on a purely subjective examination of the ophthalmoscopic aspects which are common to various types of treatment. Frequently, degenerative changes of the tumour mass are difficult to differentiate from actual recurrence. Recurrences generally start at the edge of the scar or within the scar, while new retinal tumours are observed far from the original tumour, sometimes near the ora serrata. The authors discuss the regression patterns and the ophthalmoscopic and clinical aspects of recurrent and new tumours and report their personal experience on the therapeutic approach. PMID- 1923318 TI - Effectiveness of genetic counselling. Retinoblastoma. AB - The authors studied 32 families with 36 RB patients. Among them 24 were sporadic cases; four had recurrence of RB; two had RB plus bone tumour in relatives and two were RB propositi. Two evaluations with an interval from four to 13 years were made. In the first the recurrence risk was informed as high or low. The patients' decisions were evaluated at the second consultation. The authors considered that counselling was negative in more than 50% of cases. For normal parents, prognosis of RB was severe, whereas for RB patients it was mild. PMID- 1923319 TI - Clinical variability in a family with X-linked retinal dystrophy and the locus at the RP3 site. AB - One large Australian family with X-linked retinal dystrophy was found to have extreme clinical variability in the hemizygotes. One member had the typical rod cone disease, three had the cone-rod pattern and one had macroscopic changes in the macular area only, but with low potentials in the ERG. The locus for the disease was found to be distal to L1.28 at Xp21, the site for RP3. From a study of case histories reported it seems that clinical variability can be a common feature of X-linked retinitis pigmentosa (XLRP) with the locus at Xp11.3 (RP2) or at Xp21 (RP3), and this family may well be categorized as XLRP. PMID- 1923320 TI - Carrier detection in X-linked retinitis pigmentosa by multipoint DNA analysis. Problems due to genetic heterogeneity. AB - DNA diagnosis of X-linked retinitis pigmentosa (XLRP) is hampered by its genetic heterogeneity, while a clinical subdivision is almost impossible to make. So far, diagnostic services have been offered only to those families in which linkage to one RP locus (RP2 or RP3) has been clearly established. In most families, however, the nature of the XLRP type cannot be distinguished on the basis of linkage analysis. Here the authors describe that in some families DNA diagnosis is nonetheless feasible, when polymorphic DNA markers are used which span the entire Xp21.1-Xcen region and when no recombination between these markers disturbs the phase. PMID- 1923321 TI - The Charles F. Prentice Award Lecture 1990: specific tests and specific blindnesses: keys, locks, and parallel processing. AB - Classical color vision theory incorporates the concepts of hard-wired parallel independent processing and of hard-wired opponent-processing. These two powerful concepts can be applied more generally in visual psychophysics. The concept of parallel independent processing can help to understand two extremes of visual performance: disordered vision in patients and the extraordinary visual abilities of athletes and aviators. Three illustrations of this thesis are discussed. First, evidence for dissociations of spatial vision for low-contrast and high contrast objects. Second, evidence that a binocular system for motion in depth runs in parallel with the classical disparity-driven binocular system for relative position in depth. Third, evidence that a visual system for motion defined form parallels the well known system for contrast-defined form. However, in principle these two concepts have limited value because they do not incorporate the possibility that the functional organization of the visual pathway could be modified by descending task-dependent signals. PMID- 1923322 TI - Characterization of the fundal reflectance of infants. AB - Pupillary images recorded by a linear knife-edge photoscreener for infants accommodating more or less within the bounds of chromatic aberration show three smooth offset pupillary irradiance ramps when analyzed with a color video camera and frame-grabbing hardware. Both the shape of the ramps and the lack of a second image in a shadowing experiment support the view that the retina acts as an angularly diffuse partial reflector in photorefraction. We propose a lateral image-spreading characteristic to account for observed color-dependent ramp heights and offsets and consider possible physical mechanisms for lateral spreading. PMID- 1923323 TI - Contrast/color card procedure: a new test of young infants' color vision. AB - We have developed a new test which can rapidly evaluate basic color vision in individual infants. The test consists of a series of large cards constructed with Munsell Hues. It uses a modified preferential looking procedure (FPL) and, to control brightness cues, incorporates a two-phase systematic variation of luminance. First, we evaluate an infant's ability to discriminate 9.5 by 16 degrees achromatic patches of varying luminance from a 26 by 65 degrees achromatic background of midrange luminance. In the second phase the test patch is chromatic and its luminance, relative to the background, is varied over a range of about 1.0 log cd/m2. The number of relative luminances chosen for each infant depends upon his/her performance in phase 1. Seventy 2- and 3-month-olds were tested with 4 broad-band chromatic patches, a red (dominant lambda = 660 nm), a yellow (dominant lambda = 580 nm), a green (dominant lambda = 520 nm), and a blue (dominant lambda = 475 nm). Results showed that 3-month-olds had little difficulty making any of the chromatic-achromatic discriminations but many 2 month-olds appeared to fail to discriminate the yellow and green from the background at relative luminances close to an adult brightness match. Most importantly, the test shows promise as a relatively simple, time-efficient, and portable tool for the assessment of early color vision. PMID- 1923324 TI - Stereoacuity development in young children. AB - An operant preferential looking (OPL) test with random dot stereo targets was used to gather developmental data on stereoacuity thresholds in 180 children between 18 and 65 months of age. Results indicated a steady improvement in stereoacuity with age from 250 sec arc in the youngest children tested to 60 sec arc in the oldest group of children. The greatest improvement in stereoacuity occurs at 30 months of age where mean values improve from 225 to 125 sec arc. This large change in stereo threshold appears to be attributable to the significantly higher variability in responses in the children under 30 months of age vs. the lower variability in responses in children over 30 months of age. The overall steady improvements in stereoacuity appear to be a result of the developmental changes in the variability of responses rather than actual neurophysiological changes within the visual system. PMID- 1923325 TI - Task and visual performance with concentric bifocal contact lenses. AB - We evaluated the effects of concentric simultaneous vision bifocal contact lenses on task performance, visual acuity, and stereopsis. Forty extensively screened presbyopes were fitted with CIBA Spectrum center-near bifocal contact lenses (BCL) and with distant contact lenses combined with reading spectacles (DCL) which served as the control. Thirty-two subjects completed the 8-week study. At dispensing and after 8 weeks of regular BCL wear, performance times with BCL were significantly greater than with DCL for all three near tasks. BCL generally resulted in more errors per trial. Visual acuities with BCL were reduced significantly by 0.8 to 1.4 acuity lines compared to DCL. Stereopsis was reduced significantly by 32 to 36 sec arc with BCL compared to DCL at both measurement sessions. It is likely that the decreased task performance with the simultaneous vision BCL is caused by the decreased visual acuity with these lenses. Nonetheless, 27 patients (58.7% of those selected to be fitted; 67.5% of those who were fitted) chose to wear the BCL on a regular basis at the study conclusion. Thus, even though BCL reduced task and visual performance, thoroughly screened and properly fitted presbyopic patients can become satisfied BCL wearers. However, the reduced task and visual performance with BCL should be considered when evaluating prospective BCL candidates. PMID- 1923326 TI - Prevalence of spectacle wear among U.S. Army aviators. AB - The advanced avionic and electro-optical systems installed in Army rotary wing aircraft are becoming increasingly incompatible with spectacle wear. Therefore, the prevalence of spectacle wear among Army aviators is an important consideration in the development of future systems. A review of spectacle prevalence data from the Aviation Epidemiology Data Register (AEDR) for the years 1986, 1987, 1988, and 1989 was performed. Data were consistent across all 4 years, with mean prevalence of spectacle wear being 22% for active component forces. Reserve and National Guard components displayed mean spectacle wear prevalences of 27% and 32%, respectively. These prevalence rates are higher than those previously obtained in 1985 by a similar, but slightly different paradigm. Spectacle-wearing aviators exist in greater numbers than previously documented and represent a segment of the aviation population that will have increasing compatibility problems with advanced flight systems. Therefore, system planners will need to address these incompatibilities in future hardware developments. PMID- 1923327 TI - Penetration of hydrogen peroxide from contact lenses or tear-side solutions into the aqueous humor. AB - Contact lenses were soaked in hydrogen peroxide (H2O2) solutions of 1 to 20 mM (34 to 680 ppm) and placed on isolated rabbit corneas to determine whether H2O2 could penetrate across the tissue into the artificial aqueous humor used to perfuse the endothelial surface. Corneas with intact epithelium allowed no H2O2 to cross into the perfusing fluid even with the lenses containing the highest (20 mM) concentration of peroxide. If the epithelium was removed a transient pulse of H2O2 appeared in the perfusing fluid only from lenses with 10 or 20 mM H2O2. The cornea metabolized H2O2 rapidly (the rate varying with the concentration) and thus the small quantities of H2O2 in the contact lenses (less than 400 nmol at 20 mM) are destroyed before diffusing across the entire thickness of the cornea. When the contact lens was replaced by a 0.8 ml saline containing H2O2, and renewed every 15 min, H2O2 crossed the intact cornea to the perfusing fluid when its concentration at the epithelium was between 3 and 4 mM. Should such larger quantities be presented to the epithelium (for example, in eye drops) the concentration, volume, and duration of exposure will determine whether H2O2 enters the anterior chamber. It is concluded that in the clinical situation of typical contact lens use in an eye with intact epithelium neither the corneal endothelium nor other intraocular tissues will be damaged by residual concentrations of H2O2 up to 680 ppm, whether in single or daily events. PMID- 1923328 TI - Effect of chromatic aberration on isoluminance stereothreshold. AB - The results of a previous experiment have shown that stereothreshold varies as a function of the luminance difference between a target and its background. When the luminance of the target is the same as that of the background (isoluminance) the stereothreshold was elevated by a factor of 3 as compared with a situation where there was maximum luminance difference between the target and the background. Generally, if the target and the background have the same color, stereothreshold at a particular luminance difference level was lower (stereoacuity better) than if the target and the background have different colors. This indicates a possible effect of chromatic aberration on stereothreshold which could be responsible for the 3-fold increase in threshold at isoluminance. This possibility has been investigated in this experiment. The results show that even though stereothresholds are sensitive to chromatic aberration this factor cannot explain the elevated stereothreshold at isoluminance. PMID- 1923329 TI - Contrast-sensitivity loss in a group of former microelectronics workers with normal visual acuity. AB - The measurement of contrast sensitivity at varying grating frequencies is used increasingly to study visual and neural disorders. It provides more information than conventional acuity measures. Refractive errors initially affect high spatial frequencies, whereas lower spatial frequencies are affected only when these errors are pronounced. Neurophysiological alterations are reflected by depressed sensitivity to coarse gratings. Visual dysfunction has been associated with workplace exposures to a wide range of organic solvents. In microelectronics assembly where large quantities of organic solvents are used in many aspects of the work processes, visual deficits have been observed. The objective of the present study was to compare contrast sensitivity among former microelectronics assembly workers, with normal far and near visual acuity, and a reference group from the same region, with similar acuity. No significant differences were observed between scores at the two ends of the contrast sensitivity curves; however, at the intermediate spatial frequencies, the former microelectronics workers' scores were significantly lower (Student's t-test; p less than 0.05). For the microelectronics workers, no relation was observed between age and contrast sensitivity at any spatial frequency, whereas for the reference group, contrast sensitivity scores were progressively lower with age at spatial frequencies greater than or equal to 6.0 cpd (r2 = 0.15 at 6 cpd to r2 = 0.45 at 18.0 cpd), suggesting that for the former there is some form of interference with the expected contrast sensitivity loss with age. Lower contrast sensitivity scores in intermediate spatial frequencies, observed among the former microelectronics workers, possibly reflect neural alterations, which may have resulted from exposure to neurotoxic substances. These findings suggest the need for further studies on visual functions in microelectronics workers. PMID- 1923330 TI - Treatment of vernal keratoconjunctivitis: a retrospective clinical case study. Wallace F. Molinari Ocular Pharmacology Award. AB - A retrospective clinical case study was conducted to determine which therapeutic modality was considered most efficacious in treatment of vernal keratoconjunctivitis (VKC). Therapeutic modalities included: (1) antihistamine vasoconstrictor preparations; (2) disodium cromoglycate (DSCG); and (3) steroids. Eighteen clinical patients were evaluated based on signs and symptoms. Treatment and management were based on prior experience of the attending clinician. Randomization was not used in forming the patient base for this study, because all patients were part of a private health care facility. Results indicated corticosteroids were the single most effective agents in treating VKC, yet DSCG induced less iatrogenic risk with only a slight decrease in effectiveness when the original inflammation has abated. Antihistamine-vasoconstrictor preparations had only limited success in effective treatment of VKC. The study showed that concurrent use of a steroid and DSCG provided the most efficacious treatment modality for VKC. PMID- 1923331 TI - Statistics notebook: Entry III.A: Statistical hypotheses, null vs. alternative; Entry III.B: Statistical vs. research hypothesis. PMID- 1923332 TI - Multiple image phenomenon. PMID- 1923333 TI - Wavefront aberration of the eye: a review. AB - The concept of monochromatic wavefront aberration is discussed in relation to ray aberration, and methods for its measurement in the case of the eye are described. Examples are given of the measured aberration in individual eyes: in general the aberration falls within the Rayleigh quarter-wavelength criterion for pupil diameters less than 2 to 3 mm but significantly degrades image quality for larger pupils. The use of wavefront data to explore both the modulation and phase transfer functions of the eye as a function of pupil diameter and focus is described, together with typical results. Potential applications to clinical problems such as the effects of contact lenses, intraocular implants, refractive surgery, and pathology on the optical quality of the eye are outlined. PMID- 1923334 TI - Acuities through annular and central pupils after radial keratotomy. AB - The corneal radius of curvature after radial keratotomy (RK) increases centrally in the surgery-free area while remaining relatively unchanged paracentrally and peripherally in the surgical areas. These corneal topography changes suggest that the imaging properties of the cornea should vary with the area of the cornea allowed to participate in image formation. To test this hypothesis visual acuities were measured both through a central and an annular pupil for normals and RK patients as a function of time after surgery. Annular acuities were decreased significantly after RK and remained decreased over time. Best corrected central acuity increased as a function of time after surgery, becoming significantly better than presurgery acuities but not as good as normals with similar low refractive corrections. Clinical implications include: (1) variations in visual performance (e.g., acuity, contrast sensitivity, glare) and optical quality measures (e.g., refraction, higher-order aberrations) as a function of pupil size; (2) use of a large a surgery-free area as possible; (3) careful centering of the surgery-free area on the natural pupil; (4) new contact lens designs for correcting RK patients' residual refractive error; and (5) counseling patients in general, and patients with naturally large pupils in particular, concerning possible variation in visual function with pupil size. In summary, this study indicates that postsurgery RK paracentral/peripheral corneal optics experience a loss in optical quality as compared to either normal eyes with a low refractive correction or the same eye before surgery. PMID- 1923335 TI - Relation between spherical refractive error and visual acuity. AB - The relation between a spherical refractive error and visual acuity is investigated and the results compared with previous studies. This study, unlike most of the previous studies, presents a mathematical model that includes a pupil size factor. It also examines a theoretical relation between refractive error and visual acuity which predicts that there should be a linear relation among refractive error (E), the pupil diameter (D), and minimum angle of resolution (A), over a wide range of refractive errors. PMID- 1923336 TI - Effect of ocular chromatic aberration on monocular visual performance. AB - This brief review outlines the theory of ocular chromatic aberration and describes the three primary forms in which the aberration appears: chromatic difference of focus, chromatic difference of magnification, and chromatic difference of position. Our central theme is that all three aspects of chromatic aberration have as their common basis the chromatic dispersion of light. The magnitude of each form of the aberration is related to the others by simple linear formulas in which a key parameter is the location of the pupil relative to the nodal point of the eye. The way in which retinal image quality is affected by chromatic aberration is described and we assess the impact of the aberration on visual performance. PMID- 1923337 TI - Achromatizing the human eye. AB - Ocular chromatic dispersion manifests itself as wavelength-dependent image planes, image sizes, and image positions, and it has been suggested that ocular chromatic aberration is the most important of the eye's optical aberrations. Most attempts to correct for the eye's chromatic aberration (achromatize the human eye) have concentrated on correcting the wavelength-dependent image planes or chromatic difference of refractive error (CDRx). There are two optical techniques that correct for CDRx (special achromatizing lenses and multiple channel display systems) by making the ocular image planes of all wavelengths coincident. A different approach simply avoids the effects of ocular CDRx by using small pupils which effectively make all images diffraction-limited irrespective of wavelength dependent differences in image planes. Theoretical and experimental evidence shows that achromatizing lenses provide an accurate correction for CDRx. In spite of the pre-eminence of chromatic aberrations, and the effectiveness of the corrections, no obvious improvements in vision accompany correction. We show that loss of retinal image quality due to CDRx may be subthreshold (less than ocular depth of focus). We also show that achromatizing methods can introduce their own chromatic aberrations that can easily exceed those present in the uncorrected eye. The precise location of the eye with respect to the achromatizing device determines the amount of these additional aberrations. Therefore, in order to achromatize the eye effectively, careful control of eye position is essential. PMID- 1923338 TI - Model of tonic accommodation after sustained near focus. AB - The effect of short-term near focus on tonic accommodation (TA) was previously investigated in 48 visually normal subjects. After sustained focus upon a near target for 10 min, all illumination was extinguished and the decay of accommodation was monitored for 20 min. We calculated from these results that accommodation decayed rapidly with a time constant of about 0.4 min, followed by a slower decay with a time constant of about 32 min. However, the asymptotic level remained slightly above the preadaptation level after 20 min in the dark. A feedback model with two parallel dynamic components (transient and decay), which summed with a "bias" element in the forward loop, was developed to account for the results. The gains of the dynamic elements were varied until the simulation curves matched the experimental adaptation and decay data. During the closed-loop adaptation phase, the outputs of the dynamic elements moved in opposite directions but combined to yield the overall accommodation step response. Moreover, when the model was subsequently open-looped in the dark, the transient component declined rapidly, whereas the decay component remained above the preadaptation level. When the 48 subjects were grouped equally into 4 refractive categories, somewhat different decay time courses could be simulated with changes in model parameter values. PMID- 1923339 TI - Complications of rigid gas permeable lenses for extended wear. AB - A retrospective study of 174 patients wearing rigid gas permeable lenses for a period of 2 years was carried out to determine the success rate and types of complications which typically occur. The results indicate that these types of lenses are a viable modality for extended wear, as the majority of signs which may lead to serious complications can be detected relatively early. When these signs were detected the patients were switched to daily wear and most were able to wear these lenses uneventfully. However, the results also indicate that unexpected problems can occur, and thus frequent follow-up is essential in these patients in order to avoid the potentially sight-threatening problems which have come to be associated with extended wearing of contact lenses. PMID- 1923340 TI - Factors affecting light scatter in contact lens wearers. AB - We measured forward light scatter at 3.5, 10, and 28 degrees using a portable stray light meter. Subjects included 66 normal subjects (age range 19 to 79 years), 17 established hydrophilic contact lens wearers, and 15 rigid gas permeable (RGP) contact lens wearers. Contact lens deposits were measured using a modified Rudko procedure and a Leitz/Wild Makroscope M240. Corneal health was assessed using slitlamp biomicroscopy. Results showed a significant increase in light scatter with age, particularly after the age of 40 years. Stray light scores were significantly lower in pigmented non-Caucasian subjects, particularly at larger angles. The stray light scores were significantly greater in contact lens wearers than in age-matched normals, but were not found to correlate with the amount of lens deposits. Scores from hydrophilic lens wearers after removal of their lenses were significantly higher than results from RGP wearers after removal of their lenses and from age-matched normals. This suggests the presence of subclinical corneal edema in some of these subjects. PMID- 1923341 TI - Optometric findings in the fragile X syndrome. AB - Fragile X syndrome (fra X) is one of the most significant discoveries in the area of mental retardation in the past 2 decades. Although hundreds of articles and two text-books have been written on the subject, only two studies have been published in the ophthalmic literature. This paper provides a brief review of the syndrome and reports on the ocular findings of 30 subjects with this genetic abnormality. We found that 30% of the subjects exhibited strabismus. Of those with strabismus, 70% were esotropes. Fifty-nine percent of the eyes evaluated (N = 58) showed hyperopia of +1.00 D or greater, 17% myopia of -1.00 D or greater, and 22% had at least 1.00 D of astigmatism. Major ocular health abnormalities were not identified in any of our subjects. The optometrist, as the primary eye care provider, should diagnose and treat these oculo-visual dysfunctions. PMID- 1923342 TI - Effect of reduced accommodative response on isoluminance stereothreshold. AB - A previous study has shown that stereothreshold varies as a function of the luminance difference between a target and its background. On the average, the stereothreshold at the isoluminance point is three times higher than when there is maximum luminance difference between the target and the background. One of the possible reasons for this finding is the effect of less than optimum accommodative response for isoluminant targets. This possibility has been investigated in this study. The results show that the suboptimal accommodative response cannot explain the high stereothreshold at isoluminance. PMID- 1923343 TI - Human electroretinogram responses to video displays, fluorescent lighting, and other high frequency sources. AB - Time-averaged human electroretinogram (ERG) responses were determined for several workplace visual stimuli which are temporally modulated at rates exceeding the perceptual critical fusion frequency (CFF). A clearly identifiable synchronous response was in evidence for a video display terminal (VDT) stimulus operating with a refresh rate as high as 76 Hz. A directly viewed fluorescent luminaire with controllable driving frequency elicited a synchronous response at rates as high as 145 Hz. In addition, an intense stimulus created by modulating the light from a slide projector produced responses at least as high as 162 Hz. The implications of these high-frequency responses are representing a potential basis for visual symptoms are discussed. PMID- 1923344 TI - Modeling the kinetics of topically applied ophthalmic agents. AB - The equations for the ocular pharmacokinetics of topically applied agents are developed in a matrix form which is well suited to numerical solution on small computers. Some sample computations are presented. The technique is relatively simple to extend to additional compartments. PMID- 1923345 TI - Measurement of visual acuity with logarithmic charts: comparison between methods of threshold estimation. AB - The variability of the repetition of visual acuity measurements with a log MAR acuity chart with five optotypes in each row of acuity was studied in four groups of subjects. In three groups the threshold was calculated by probability of seeing curves, but the optotypes were read in different orders. For the fourth group the acuity was taken as the smallest row discriminated. Estimating the threshold by a probability of seeing curve did not improve the threshold's stability. Poorer acuity was detected when the optotypes were read vertically. It is suggested that clinical visual acuity charts are not suitable tools for generating data points to be fitted by probability of seeing curves. PMID- 1923346 TI - Accommodative performance for chromatic targets in diabetes mellitus: a preliminary report. AB - Our objective was to evaluate the diagnostic potential of a new vision testing procedure for detecting subclinical visual dysfunction in patients with insulin dependent diabetes mellitus (IDDM) and minimal or absent retinopathy. We used a method which challenged both the ocular focusing and color discrimination systems simultaneously. A computerized laser speckle optometer which measured changes in ocular refraction on a subjective criterion of speckle movement rather than perceived blur was used to measure the accuracy of steady-state accommodative responses. Five volunteers between 15 and 23 years of age who had IDDM and minimal background retinopathy participated in this study. Our results for this small group of diabetics showed that: (1) the overall binocular accommodative response profiles of diabetics for colored targets through increasing negative power ophthalmic lenses did not differ markedly from those of a control population; (2) diabetics exhibited a high sensitivity for perception of optical defocus; (3) the blood glucose level influenced the extent and accuracy of accommodative responses; and (4) the overall accommodative precision, when compared to a group of nondiabetics in the same age range, showed evidence of being more reliant on target colors. The theoretical and clinical implications of these findings are discussed. PMID- 1923347 TI - Intraretinal foreign bodies. PMID- 1923348 TI - Surfactant and ROP incidence. PMID- 1923349 TI - The relative value of quality care. PMID- 1923350 TI - Retrobulbar hemorrhage. AB - Retrobulbar hemorrhage associated with retrobulbar anesthesia has been construed as a contraindication to cataract surgery. Cancellation of the surgery results in disappointment for both the patient and surgeon. A retrospective study of 60 eyes was undertaken to evaluate the safety of proceeding with small-incision phacoemulsification surgery after retrobulbar hemorrhage when specific criteria are met. If digital massage achieved a soft globe that was easily retropulsed and the eyelids were loose and easily mobilized, the surgery was performed as scheduled. If the globe remained firm within a tense orbit and proptosis with tight lids was present, surgery was cancelled. Fifty-seven cases with retrobulbar hemorrhage met these criteria and underwent phacoemulsification with implantation of a posterior chamber intraocular lens. The lack of intraoperative and postoperative complications suggests that small-incision cataract surgery can be safely performed when preceded by a limited retrobulbar hemorrhage. PMID- 1923351 TI - Myopic photorefractive keratectomy with the excimer laser. One-year follow-up. AB - To evaluate the efficacy, predictability, and stability of myopic photorefractive keratectomy (PRK), the authors completed a 1-year follow-up study on a consecutive series of 26 sighted eyes undergoing this procedure. The results of this follow-up are presented. In addition, side effects and complications in another 255 sighted eyes with a follow-up of 3 months to 1 year are reported to judge the safety of the procedure. Twenty-four of 26 eyes (92%) were within +/- 1.0 diopter (D) of the intended final refraction (baseline, -1.4 to -9.25 D). Fifty-eight percent of the eyes were stable within +/- 0.25 D between 6 and 12 months. One year after surgery, none of the patients lost or gained more than one line of best corrected (spectacle) visual acuity. Uncorrected visual acuity improved to 20/40 or better in 96% of the eyes and to 20/20 or better in 48% of the eyes (not including the eyes that were intentionally undercorrected). However, visual acuity with glare decreased from 20/27 preoperatively to 20/31 after 1 year. Scarring occurred in 2.8% of the treated corneas. Risk factors for scarring include noncompliance with postoperative steroid medication, high myopic corrections, and high steroid responders (3.1%). Collagen vascular and other autoimmune diseases are a contraindication for PRK. PMID- 1923352 TI - Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study five years after surgery. The Perk Study Group. AB - In the Prospective Evaluation of Radial Keratotomy (PERK) Study, 793 eyes of 435 patients with 2 to 8 diopters (D) of myopia received a standardized surgery consisting of 8 incisions with a diamond-bladed knife set at 100% of the thinnest paracentral ultrasonic corneal thickness measurement and a diameter of the clear zone of 3.0 to 4.5 mm; 97 eyes (12%) received an additional 8 incisions. There were 757 eyes (95%) followed for 3 to 6.3 years. After surgery, uncorrected visual acuity was 20/40 or better in 88% of eyes. The refractive error was within 1 D of emmetropia for 64% of eyes; 19% were myopic and 17% were hyperopic by more than 1 D. Between 6 months and 5 years after surgery, 22% of the eyes had a refractive change of 1 D or more in the hyperopic direction. For 25 eyes (3%) there was a loss of 2 or more lines of best spectacle-corrected visual acuity. PMID- 1923353 TI - Progression of visual acuity after penetrating keratoplasty. AB - A consecutive series of 721 eyes was followed for visual acuity changes after keratoplasty in four groups: keratoconus, Fuchs' dystrophy, pseudophakic bullous keratopathy with retained intraocular lenses, and aphakic/pseudophakic bullous keratopathy with secondary implants during keratoplasty. Follow-up ranged from 12 to 84 months. Keratoconus eyes showed the quickest recovery of visual acuity: by 12 months, 91% attained a best-corrected vision of 20/40, and the mean lines of visual acuity for the group plateaued thereafter. The other three groups showed continuing improvement in vision through 24 months. From 3 months through 3 years after keratoplasty, the keratoconus and Fuchs' groups consistently showed better visual acuity levels than either the retained or the secondary implant groups (P less than 0.0001). Reporting changes in visual acuity over time offers multiple advantages compared with providing best-attained or last-recorded visual acuities after keratoplasty. PMID- 1923354 TI - Results of penetrating keratoplasty associated with silicone oil retinal tamponade. AB - A review of 14 patients who underwent corneal transplantation after intravitreal silicone oil tamponade included an average follow-up of 28 months. Mean graft survival was 25 months (range, 2 to 61 months). Frequency of graft failure was 43% (6 of 14) with a mean occurrence at 14.5 months (range, 2 to 36 months). Allograft rejections occurred in four patients, two of whom progressed to graft failure. The frequency of graft failure was 25% (2 of 8) when silicone oil was removed at the time of keratoplasty compared with 67% (4 of 6) when silicone oil was retained. PMID- 1923355 TI - Immunopathology of atopic keratoconjunctivitis. AB - Conjunctival biopsies from 11 patients with atopic keratoconjunctivitis (AKC) and from 13 age-matched healthy individuals undergoing cataract surgery were analyzed by light microscopy and immunohistochemical techniques. Histology of AKC specimens showed goblet cell proliferation, epithelial pseudotubular formation, eosinophil and mast cell invasion of the epithelium, and pronounced mononuclear cell infiltration of the substantia propria, often with frank granuloma formation. Epithelium of AKC conjunctiva showed significantly more T cells (CD3+, CD5+), T-helper cells (CD4+), macrophages (Mac-1+, CD14+), activated T cells, (CD25+), and dendritic cells (CD1+), and a higher helper/suppressor ratio than did control subjects. In the substantia propria, AKC specimens showed dramatically increased inflammatory cell infiltration with significantly more cells staining, in order of frequency, for T-cells (CD3+, CD5+), T-helper cells (CD4+), T-suppressor/cytotoxic cells (CD8+), macrophages (CD14+, Mac-1+) activated T cells (CD25+), B cells (CD22+), and dendritic cells (CD1+, HLA-DR+). Fifty-three percent of T cells in the substantia propria expressed the interleukin-2 receptor protein (CD25+). These findings indicate that the chronic conjunctivitis of AKC is complex, with activated T-cells and macrophages dramatically participating in the process. Successful long-term control of the potentially binding conjunctival inflammation of this disease is likely to require therapeutic strategies directed toward more than just the mast cell component of the process. PMID- 1923356 TI - Clinical and histopathologic studies of two families with lattice corneal dystrophy and familial systemic amyloidosis (Meretoja syndrome). AB - Lattice corneal dystrophy associated with familial systemic amyloidosis (Meretoja syndrome) has rarely been described other than in patients of Finnish origin. The authors report two North American patients with this disease who manifest blepharochalasis, lattice corneal dystrophy, open-angle glaucoma, and cranial neuropathy. In one patient, a corneal intraepithelial and subepithelial pseudodendrite was managed by superficial keratectomy, and this same patient benefited from surgical brow suspension for facial muscular weakness. In the second patient, penetrating keratoplasty was complicated by a neurotrophic persistent epithelial defect. Corneal tissue from both superficial keratectomy and penetrating keratoplasty exhibited ultrastructurally characteristic amyloid filaments and associated elastoid material. Transmission electron microscopy of conjunctiva and skin biopsies similarly revealed amyloid deposits associated with most basement membranes, the perineurium and endoneurium of most peripheral nerves, and the intima and media of arteries. By immunoperoxidase staining, the corneal amyloid deposits were positive for the amyloid P-component protein but negative for the nonimmunoglobulin amyloid A protein and prealbumin. Serum prealbumin and amyloid A related protein were normal. PMID- 1923357 TI - Posterior polymorphous dystrophy and Alport syndrome. AB - Seventeen Thai patients from nine families with Alport syndrome underwent complete ocular examination and specular microscopy. Fourteen (82.3%) patients had ocular changes. Eleven (64.7%) had endothelial vesicles compatible with posterior polymorphous dystrophy. Four of these also had subepithelial opacities, a previously undescribed phenomenon. Other ocular changes included lenticonus and macular and midperipheral retinal flecks. A second group of 18 consecutive patients from 14 families with posterior polymorphous dystrophy detected during routine ocular examination underwent renal evaluation. Five had hematuria, four of whom had sensorineural hearing loss. Two of the four patients also had characteristic renal biopsy findings. Another had sensorineural hearing loss without hematuria, and renal biopsy showed a thin glomerular basement membrane. Posterior polymorphous dystrophy is a common but frequently overlooked finding in Alport syndrome. The frequent association of these two hereditary conditions suggests a common defect in basement membrane formation. Patients with posterior polymorphous dystrophy should be examined for renal abnormalities and hearing loss. PMID- 1923358 TI - Congenital macronodular juvenile xanthogranuloma of the eyelid. AB - A large congenital eyelid mass prevented an infant from elevating his eyelid successfully. A small punch biopsy was initially interpreted as "consistent with a dermatofibrosarcoma protuberans." On the basis of this diagnosis, radical surgery was advised. Dermatofibrosarcoma protuberans, however, rarely affects children and seldom appears in the head and neck area. Because of the discrepancy between clinical and pathologic diagnoses, additional biopsies were performed, which disclosed the lesion to be a juvenile xanthogranuloma. The mass regressed after intralesional injections of corticosteroids. This is the first clinicopathologic description of congenital macronodular juvenile xanthogranuloma affecting the eyelids. The variability in the histologic composition of this large lesion may lead to a mistaken diagnosis of an aggressive condition that may provoke unnecessary radical surgery. PMID- 1923359 TI - Congenital ptosis. Long-term results of treatment using lyophilized fascia lata for frontalis suspensions. AB - This report extends a prospective collaborative study published in 1982 of congenital ptosis repair using lyophilized human fascia lata to investigate the permanency of banked human fascia lata. Fifty-six patients are described with a mean postoperative follow-up of 7.2 years and a median follow-up of 8.3 years. Significant recurrence of ptosis was documented in 24 of 56 (43%) patients. New failures continue to be recognized even in the eighth postoperative year. Life table and survival analysis predicts a success rate from frontalis suspension surgery using lyophilized human fascia lata of 90% at 2 to 3 years, 70% at 5 to 6 years, and 50% at 8 to 9 years. PMID- 1923360 TI - Congenital nasolacrimal duct cysts in dacryocystocele. AB - Cystic intranasal masses were found in seven newborn infants with congenital dacryocystocele. The cysts were a direct extension of the nasolacrimal duct, located beneath the inferior turbinate. Nasal obstruction was present in three infants and was severe enough to cause respiratory distress in two neonates with bilateral cysts. Using fiberoptic nasal endoscopy, treatment consisting of probing, irrigation, and marsupialization of the cysts was successful in all infants. The authors believe this rarely reported anomaly is a more common finding in dacryocystocele than previously recognized and advocate careful nasal examination in all infants with congenital dacryocystocele. Early diagnosis and treatment of this condition is critical in the infant with nasal obstruction. PMID- 1923361 TI - The pathogenesis of canalicular laceration. AB - Canalicular lacerations are seen commonly in ophthalmic practice, but the pathogenesis of canalicular lacerations has not been explored. The authors retrospectively reviewed 25 cases of canalicular laceration seen at their institutions. Only 4 patients (16%) had injuries attributable to direct trauma; the remaining 21 patients (84%) had diffuse trauma or trauma to the eyelid remote from the canaliculus. The authors postulate that, in many of their cases, canalicular "lacerations" resulted from indirect trauma, where the eyelid was ruptured when it was stretched acutely to the point of avulsion. Two experimental models were derived to test this hypothesis. The results suggest that the canalicular portion of the eyelid is a particularly vulnerable location, and that injuries morphologically similar to canalicular "lacerations" occur predictably if the eyelid is traumatized indirectly or diffusely to the point of rupture. PMID- 1923362 TI - Orbicularis oculi muscle extirpation in a combined procedure for involutional entropion. AB - Many factors are important in the pathophysiology of involutional entropion, including defects of the lower eyelid retractors, canthal tendon laxity, and acquired enophthalmos. The role of the overriding preseptal orbicularis oculi muscle is often ignored in modern techniques of entropion repair. The author describes a technique of extirpation of the preseptal orbicularis oculi muscle combined with repair of the lower eyelid retractors and a lateral tarsal strip procedure for the repair of primary and recurrent involutional entropion. Lateral canthal tendon laxity is recognized in most patients in this age group and must be corrected to avoid postoperative overcorrection and ectropion. Removal of the preseptal muscle had no clinical effect on the lacrimal pump and did not cause any significant cicatricial eyelid abnormalities. This combined procedure has been used in 50 eyelids of 40 patients with excellent functional and cosmetic results. Orbicularis extirpation is not advocated in combination with a marginal rotation procedure. PMID- 1923363 TI - Asymptomatic orbital cavernous hemangiomas. AB - Computed tomographic (CT) scanning and magnetic resonance imaging (MRI) are commonly performed to evaluate neurologic symptoms. Rarely are asymptomatic orbital tumors discovered, creating uncertainty about their management. Eleven patients are presented who were referred for asymptomatic orbital tumors discovered on either CT scanning or MRI performed for unrelated symptoms of headache, vertigo, peripheral numbness, seizures, stroke, or hallucinations. The asymptomatic orbital tumors were diagnosed clinically and radiologically as cavernous hemangiomas. All the patients were followed clinically and neuroradiologically for an average of 37 months (range, 8 to 120 months). None of the tumors enlarged during this time. The authors conclude that patients who have asymptomatic cavernous hemangiomas, discovered by coincidence during neuroimaging, that bear no relation to the indication for obtaining the CT scan or MRI, can be safely followed by observation as an alternative to surgical excision. PMID- 1923364 TI - The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XIII. Relationship of serum cholesterol to retinopathy and hard exudate. AB - Serum total and high-density lipoprotein (HDL) cholesterol were measured in a sample of individuals examined between 1984 and 1986 for the Wisconsin Epidemiologic Study of Diabetic Retinopathy. There was a significant trend for increasing severity of diabetic retinopathy and of retinal hard exudate with increasing cholesterol in insulin-using persons. Cholesterol levels were not related to the severity of either ocular condition in older-onset patients. High density lipoprotein-cholesterol was unrelated to the severity of either lesion. In multiple logistic regression analyses, cholesterol was not a significant factor in describing the severity of retinopathy in any group but was a significant factor in describing the severity of retinal hard exudate. Glycosylated hemoglobin and diastolic blood pressure were significant descriptors of the severity of retinopathy in younger-onset patients in these multivariate analyses. Diastolic blood pressure added significantly to explaining the severity of hard exudate in older-onset insulin users. These data support the current management strategies for diabetes, which include control of level of glycemia, blood pressure, and blood lipids. PMID- 1923365 TI - Oscillatory potentials and permeability of the blood-retinal barrier in noninsulin-dependent diabetic patients without retinopathy. AB - Electroretinography and vitreous fluorophotometry were performed in 36 eyes of 36 noninsulin-dependent diabetic patients and in 32 eyes of 32 healthy control subjects between the ages of 30 and 59 years. Fluorescein fundus angiograms showed no abnormalities in either group. Peak implicit time of the first deflection of the oscillatory potential, interpeak interval between the first and second deflections, and the sum of the amplitudes of the upward deflections were analyzed. Inward permeability of the blood-retinal barrier was calculated by vitreous fluorophotometry and computer simulation. The peak implicit time of the first deflection and the interpeak interval between the first and second deflections of the oscillatory potential were significantly longer in diabetic patients than in control subjects (P less than 0.01). No significant difference in inward permeability of the blood-retinal barrier existed between the two groups. These results indicate that a selective delay in the peak implicit time of the oscillatory potential (neurosensory retinal abnormality) may be present in noninsulin-dependent diabetic patients, representing retinal functional changes before changes in blood-retinal barrier permeability are apparent. PMID- 1923366 TI - Posterior segment manifestations of inflammatory bowel disease. AB - Thirteen patients with inflammatory bowel disease and posterior segment disease were subject to a retrospective review. Eight patients had Crohn's disease and five had ulcerative colitis. In six patients, the inflammatory bowel disease was active when ocular inflammation occurred. Patients had one or more posterior segment findings that included serous retinal detachment (8), choroidal infiltrates (6), retrobulbar neuritis (1), papillitis (1), retinal pigment epithelium disturbance (1), and choroidal folds (1). Posterior segment disease responded to systemic and periocular corticosteroids in 9 of 13 cases. Four patients whose disease relapsed after corticosteroid therapy was suspended responded to bowel resection. Ophthalmologists should be aware of the wide spectrum of posterior segment abnormalities associated with inflammatory bowel disease that may require and respond to anti-inflammatory agents. PMID- 1923367 TI - Role of chorioretinal biopsy in inflammatory eye disease. AB - Two patients who had similar clinical presentations of bilateral multiple chorioretinal lesions and needed a correct diagnosis underwent chorioretinal biopsy. The biopsy from one patient demonstrated mainly a B cell infiltrate in choroidal and subretinal nodules, while the biopsy from the second patient showed mainly macrophages in the retina. These findings directed the therapeutic approach taken in each patient. Although chorioretinal biopsy is an invasive procedure with the potential for serious complications, the resultant finding may aid in the diagnosis and guide the subsequent management of certain patients presenting with serious ocular findings of undefined etiology. PMID- 1923368 TI - Clinicopathologic correlation of retinal to choroidal venous collaterals of the optic nerve head. AB - An optic nerve meningioma developed in an elderly woman and was followed for 13 years until her death. The optic nerve was initially normal. Over time it became swollen and then atrophic and developed retinal venous to choroidal venous collaterals. Five hundred serial sections were prepared through the optic nerve and for approximately 1.5 mm superiorly and inferiorly to the optic nerve to trace the course of the collaterals that were seen ophthalmoscopically and angiographically in the optic nerve head. This clinicopathologic study shows clearly that the abnormal channels are, in fact, retinal venous to choroidal venous collaterals (bypass channels). Four collaterals extended around the end of Bruch's membrane at the optic nerve head. Two more collaterals extended through the retinal pigment epithelium to become continuous with a subretinal pigment epithelial neovascular membrane, the vessels of which connected with the choroidal vessels through a defect in Bruch's membrane. PMID- 1923369 TI - Optic disc edema after bone marrow transplantation. Possible role of cyclosporine toxicity. AB - Bone marrow transplantation has become widely used in the treatment of aplastic anemia and leukemia. Cyclosporine is used as prophylaxis against graft-versus host disease. The authors report on eight cases of optic disc edema in patients taking cyclosporine after allogenic bone marrow transplant. Thorough evaluation revealed a possible alternate cause in two cases. In all cases, the optic disc edema resolved after discontinuing or decreasing the cyclosporine. Although cyclosporine has not previously been associated with optic disc edema, it has been implicated as the cause of a variety of neurologic side effects. Bone marrow transplant patients taking cyclosporine should be followed for the development of optic disc edema. PMID- 1923370 TI - Large recession of the horizontal recti for treatment of nystagmus. AB - Ten patients had large recession of four horizontal recti at one procedure for treatment of nystagmus. Six patients had congenital motor nystagmus, two had oculocutaneous albinism, and two had optic nerve hypoplasia. Anomalous head posture with null point was also present in five patients. The rectus muscles were placed at or behind the equator in all but one case. Three patients with both esotropia and nystagmus had the medial recti placed 1 mm behind the equator and the lateral recti or at 1 mm anterior to the equator. Visual acuity improved an average of 1 line at distance and/or near in 8 patients who cooperated for testing. Although nystagmus was not eliminated in any patient, its its amplitude decreased in eight of ten patients, and anomalous head posture improved in three of five patients. In all patients, near vision was better than distance vision both preoperatively and postoperatively. Ductions were diminished minimally after the large recession and there were no other complications from surgery. PMID- 1923371 TI - Visual development of infants with severe ocular disorders. AB - Among 11 patients who presented as blind in early infancy, with Leber's congenital amaurosis (5 patients), optic nerve hypoplasia (4 patients), or macular colobomata (2 patients), 8 developed visually guided behavior and measurable grating acuity by age 5 to 46 months. All children with measurable grating acuity demonstrated visually guided mobility. Grating acuity was predictive of later visual performance in 10 of 11 patients by age 12 to 16 months. The best grating acuity attained by 7 months was 1.3 to 3.0 cycles/degrees (20/460 to 20/200) and 0.13 cycles/degrees (20/4700) by month 8. Two patients with Leber's congenital amaurosis and one with optic nerve hypoplasia remained blind. No clinical features existed to differentiate these three patients from the eight whose visual status improved. Posterior visual pathway maturation may underlie the improvement. PMID- 1923372 TI - The Beaver Dam Eye Study: visual acuity. AB - Few current population-based data on visual impairment are available. Visual acuity and impairment were measured in 4926 people between the ages of 43 and 86 years in the defined population participating in the Beaver Dam Eye Study. Visual acuity was measured after refraction, using standardized protocols. Of a possible maximum score of 70 (20/10), the mean number of letters correctly identified (right eye) varied from 55.7 (20/20, n = 1515) in people between the ages of 43 and 54 years to 41.2 (20/40, n = 795) in people 75 years of age or older. Age specific mean visual acuity scores were consistently and significantly lower in women, who identified three fewer letters on the average than men. Rates of any visual impairment (20/40 or worse in the better eye) or legal blindness (20/200 or worse in the better eye), increased from 0.8% and 0.1%, respectively, in people between the ages of 43 and 54 years to 21.1% and 2.0%, respectively, in people 75 years of age or older. Multivariate analyses showed both sex (women) and age (older) to be significant and independent predictors of poorer visual acuity. PMID- 1923373 TI - Parasites of domestic and wild animals in South Africa. XXV. Ixodid ticks on sheep in the north-eastern Orange Free State and in the eastern Cape Province. AB - The tick burdens of 115 Merino sheep, slaughtered over a period of 15 consecutive months on a farm in the north-eastern Orange Free State, were determined. A total of 7 ixodid and 1 argasid tick species were recovered and the seasonal abundances of Boophilus decoloratus, Hyalomma marginatum rufipes, Margaropus winthemi and Rhipicephalus evertsi evertsi were determined. One hundred and forty-nine Merino sheep were slaughtered over periods varying from 10 to 25 months on 3 farms in Eastern Province Thornveld in the eastern Cape Province and their tick burdens determined. Fourteen ixodid tick species were recovered from these animals and the seasonal abundances of Amblyomma marmoreum, B. decoloratus, Haemaphysalis silacea, R. evertsi evertsi and Rhipicephalus nitens were ascertained. On a farm in Valley Bushveld in the eastern Cape Province, 2 Dorper sheep were slaughtered each month for a period of 24 consecutive months. These 48 sheep harboured 10 ixodid tick species and the seasonal abundances of A. marmoreum, H. silacea, Rhipicephalus appendiculatus and Rhipicephalus glabroscutatum were determined. A total of 17 ixodid tick species, of which 12 had reached the adult stage, where recovered from the sheep on the 5 farms. PMID- 1923374 TI - Parasites of domestic and wild animals in South Africa. XXVI. The mosaic of ixodid tick infestations on birds and mammals in the Mountain Zebra National Park. AB - Sixteen species of ixodid ticks were collected over varying periods of time from 6 species of ground-frequenting birds and 15 species of small and large mammals in the Mountain Zebra National Park, Karoo, Cape Province. Margaropus winthemi followed by Rhipicephalus glabroscutatum and Rhipicephalus evertsi evertsi were the most abundant species. The host preferences of 14 tick species and the seasonal abundances of 13 species were determined. Small numbers of immature stages of only a few tick species were generally recovered from ground frequenting birds, mice and rats. Amongst the slightly larger animals the smallest number of ticks and species were recovered from springhares and the largest numbers from scrub hares. Amongst the larger mammals, very few ticks were harboured by springbuck and black wildebeest, while heavy infestations of several species were encountered on Cape mountain zebras and eland. PMID- 1923375 TI - Parasites of domestic and wild animals in South Africa. XXVII. Ticks on helmeted guineafowls in the eastern Cape Province and eastern Transvaal Lowveld. AB - Seventy-six helmeted guineafowls (Numida meleagris) were shot in the Andries Vosloo Kudu Reserve and on an adjacent farm in the eastern Cape Province during the period May 1985 to January 1987 and their tick burdens determined. A total of 10 ixodid tick species were recovered, of which Amblyomma hebraeum, Amblyomma marmoreum and Haemaphysalis silacea were the most abundant. The seasonal abundances of these 3 species and of Hyalomma marginatum rufipes were ascertained. A marked difference between the total number of A. hebraeum recovered from the birds in the reserve and those on the farm is ascribed to the treatment of domestic stock on the farm with an acaricide. The tick burdens of 118 helmeted guineafowls, shot in the southern part of the Kruger National Park, eastern Transvaal Lowveld, from August 1988 to August 1990, were also determined. Ten ixodid tick species and the larvae of an argasid species were recovered. A. hebraeum, A. marmoreum and the Argas sp. were the most abundant and their seasonal abundances and that of Rhipicephalus zambeziensis were determined. Only 2 of the 54,659 ixodid ticks recovered from the birds at the 3 localities were adults and the presence of these is ascribed to accidental infestations. PMID- 1923376 TI - The prevalence of blood parasites in helmeted guineafowls, Numida meleagris, in the Kruger National Park. AB - Bloodsmears were taken from separate groups of five helmeted guineafowls, Numida meleagris, shot at approximately monthly intervals at Skukuza and near Lower Sabie in the Kruger National Park during the period August 1988 to August 1990. Ninety-eight (86%) of 114 guineafowls had single or multiple infections of Aegyptianella sp., Haemoproteus pratasi, Hepatozoon sp., Leucocytozoon neavei, Plasmodium circumflexum and Trypanosoma numidae. The apparent seasonal prevalence of Aegyptianella sp., H. pratasi and L. neavei, the three most commonly occurring parasites (42%, 49% and 56% of birds infected respectively), is probably dependent on the presence of their respective vectors. PMID- 1923377 TI - Overberg research projects. X. Faecal egg counts in the interpretation of nematode worm burdens in sheep. AB - Worm egg counts were compared with nematode worm burdens from data collected from greater than 400 sheep killed in experiments on the epidemiology of nematode parasites in the Overberg, in the winter rainfall area of the southern Cape Province. Data were analysed in several ways but no method could be found to accurately estimate the number of nematodes present from the faecal egg count in respect of individual sheep. However, the mean natural log egg count (epg) can roughly predict the mean natural log nematode count in groups of sheep. PMID- 1923378 TI - Afrotropical Culicoides: C (Avaritia) miombo sp. nov., a widespread species closely allied to C. (A.) imicola Kieffer, 1913 (Diptera: Ceratopogonidae). AB - Culicoides (Avaritia) miombo sp. nov. is described and illustrated from both sexes collected in northern Malawi. Two references in the literature have previously referred to this new species as either C. brosseti Vattier & Adam or C. imicola Kieffer. A further 4 references are discussed that most likely deal with C. miombo sp. nov. and not C. brosseti. C. miombo sp. nov. is apparently widespread in subtropical and tropical Africa and is now recorded from Zimbabwe, Botswana, South Africa, Nigeria and the Ivory Coast. There are also probable records from Angola, Burkina Faso, Zambia and eastern Madagascar. On the African mainland, both north and south of the equator, the pattern of distribution of C. miombo sp. nov. correlates strongly with that of drier Guineo-Congolian rainforest, and Sudanian and Zambezian woodlands, the latter known as miombo in southern Africa. These phytochoria and associated biota are sensitive to frost and experience relatively high temperatures and rainfall-3 factors that appear to limit the distribution of C. miombo sp. nov. to north of the 20-22 degrees C mean annual temperature isotherms in southern Africa. The new species is a member of the Imicola group which consists of 6 species confined to the Afrotropical (including Madagascar), Oriental and eastern Palaearctic regions. One species has in historic times spread to Australia. The worldwide distribution of each species is briefly discussed. It is suggested that the Imicola and Orientalis groups are separate lineages within the subgenus Avaritia. Culicoides miombo sp. nov. is compared with its closest African congeners C. imicola, C. pseudopallidipennis Clastrier and C. bolitinos Meiswinkel; 15 character states are used to separate C. miombo sp. nov. and C. imicola. The female antennal and palpal measurements of C. miombo sp. nov. are subjected to statistical analysis to highlight their taxonomic usefulness. The larval habitat of C. miombo sp. nov. is unknown. PMID- 1923379 TI - T cell-mediated immunity to Cowdria ruminantium in mice: the protective role of Lyt-2+ T cells. AB - The inability of athymic nude mice to make a drug-aided recovery from infection with either the Kumm or the Welgevonden stocks of Cowdria ruminantium and their inability to mount an immune response, suggest that immunity in heartwater is cell-mediated. The adoptive transfer of immunity with the spleen cells of mice immune to the Welgevonden stock is supportive evidence. Immune spleen cells depleted of Lyt-2+ T cells are unable to confer resistance to challenge to recipient mice, whereas the depletion of L3T4+ T cells had no effect on the protection conferred by immune spleen cells. This is conclusive evidence that immunity in heartwater is largely cell-mediated. Immune serum, C. ruminantium and complement incubated in the presence of mouse peritoneal macrophages, inhibits the infectivity of the heartwater agent, but not in the absence of macrophages. The decreased resistance to challenge of immune mice treated with gloxazone adds further support to the concept that in heartwater persistence of C. ruminantium in the host is associated with immunity. PMID- 1923380 TI - Relative resistance of six cattle breeds to the tick Boophilus decoloratus in South Africa. AB - Adult females of the tick Boophilus decoloratus were removed from 6 breeds of cattle on 2 farms in the Northern Transvaal. Highest numbers of female ticks were collected from Simmentaler, followed by Santa Gertrudis, Bonsmara, Afrikaner, Brahman and Nguni. Resistance levels of each breed to B. decoloratus was positively correlated with the amount of Bos indicus genes in the breed, with the exception of Nguni, which is a sanga type but not pure B. indicus. PMID- 1923381 TI - Ultrastructural morphology of Cowdria ruminantium in midgut epithelial cells of adult Amblyomma hebraeum female ticks. AB - Amblyomma hebraeum male and female ticks, experimentally infected as larvae with the Ball 3 stock of Cowdria ruminantium, were fed on a heartwater susceptible sheep. The initial attachment of the males was required as a pre-requisite for female attachment. Reticulate bodies were the predominant morphologic form of Cowdria observed in gut epithelial cells after 1-3 days of feeding. Single intermediate bodies and no elementary bodies were observed. Organisms were found within a membrane-bound vacuole and each organism had a double-unit membrane. Infrequently colonies contained homogeneous electron-dense inclusions. Groups of Cowdria organisms within a haemocyte suggested a possible dissemination of organisms from the gut to various other tissues by haemocytes. PMID- 1923382 TI - Parasites of South African wildlife. VIII. Helminth and arthropod parasites of warthogs, Phacochoerus aethiopicus, in the eastern Transvaal. AB - Helminth and arthropod parasites were collected from 41 warthogs, Phacochoerus aethiopicus, in the Hoedspruit Nature Reserve, eastern Transvaal. This reserve consists of a military base, which is a restricted area and is surrounded by a reserve, which is open to the public. Eleven nematode species, 1 or 2 cestode species and the larvae of 2 cestode species were recovered from the animals in the reserve, and 8 nematode species and 1 or 2 cestode species were recovered from those in the military base. Oesophagostomum spp. were generally most abundant in warthogs in the reserve during the cooler months of the year, while Probstmayria vivipara also occurred in peak numbers during the cooler months, with an additional peak in October and November 1988 in warthogs in the reserve and the base, respectively. No pattern of seasonal abundance could be determined for the other helminth species. The warthogs also harboured 8 ixodid and 1 argasid tick species, 3 flea species and 1 louse species. Adult and immature Haematopinus phacochoeri were most numerous during August and September, and the largest numbers of adult Rhipicephalus simus were present from December to April. PMID- 1923383 TI - Parasites of South African wildlife. IX. Helminths of kudu, Tragelaphus strepsiceros, in the eastern Cape Province. AB - The helminths of 25 kudu, Tragelaphus strepsiceros, from 3 localities in the eastern Cape Province were collected, counted and identified. The majority of kudu harboured no worms, and the burdens of those infected were small. A race of Cooperia rotundispiculum, a Dictyocaulus sp., a Haemonchus sp., Nematodirus helvetianus and Ostertagia ostertagi were recovered. Two parasites, Nematodirus helvetianus and Ostertagia ostertagi can be added to the list of helminth parasites of kudu in South Africa. PMID- 1923384 TI - Parasites of South African wildlife. X. Helminths of red duikers, Cephalophus natalensis, in Natal. AB - The helminths of the following red duikers, Cephalophus natalensis, were examined: 24 from 3 game reserves in Natal and 1 that had originated from Charters Creek, Natal, shortly before it died in the National Zoological Gardens, Pretoria. The 21 animals from Charters Creek harboured 16 nematode species, a nematode genus, 2 cestode species and paramphistomes. The 2 red duiker from Fanies Island harboured 4 nematode species, 3 nematode genera and 1 cestode species, while the single red duiker from Ndumu was infected with 3 nematode species. The antelope from the National Zoological Gardens, Pretoria, harboured 2 nematode species, 1 nematode genus and 1 cestode species. A race of Cooperia rotundispiculum was the most abundant nematode in duikers from all the reserves. Hyostrongylus rubidus is a new parasite record in South Africa and in red duikers, and was present in 80% of the antelope. Although primarily a parasite of swine, Hyostrongylus rubidus should be regarded as a definitive parasite of these antelope. PMID- 1923385 TI - The pathology of Cestrum laevigatum (Schlechtd.) poisoning in cattle. AB - The clinical features and pathological findings of 6 steers drenched with dried plant material of Cestrum laevigatum are described. Doses ranging from 0.5 to 10 g/kg/day were given intraruminally for 1 to 38 days. Animals that received 5 to 10 g/kg/day showed nervous signs including ataxia, muscle tremors, hypersensitivity and intermittent chewing. Clinical signs in the steers which received 0,5 to 4 g/kg/day were mild. High doses induced moderate to severe hepatosis characterized by centrilobular to midzonal coagulative necrosis, haemorrhage and congestion. At lower rates only mild hepatic lesions, characterized by disappearance of hepatocytes and collapse of the reticulin stroma in the centrilobular areas were evident. Ultrastructural changes were primarily limited to the hepatocytes and comprised degeneration, necrosis and fatty change. Degeneration and necrosis of endothelial cells and disruption of sinusoidal walls were occasionally observed. PMID- 1923386 TI - Sweating sickness: relative curative effect of hyperimmune serum and a precipitated immunoglobulin suspension and immunoblot identification of proposed immunodominant tick salivary gland proteins. AB - Although of low morbidity, sweating sickness is readily induced in calves by infestation with positive Hyalomma truncatum adult ticks. This epitheliotrophic disease has no specific cure except by the administration of hyperimmune serum obtained from animals which have recovered and are subsequently immune to the disease. Treatment with hyperimmune serum, however, has associated problems of donor availability, possible serum contamination and i.v. administration of a relatively large volume. This paper compares the treatment and cure of sweating sickness using unrefined hyperimmune serum and that of an experimental suspension. The latter proved relatively inefficient probably due to a low concentration of effective immunoglobulins. Immunoblot analyses of the sera of affected animals, using tick salivary glands as antigen during the course of the trial revealed 4 tick salivary gland proteins with molecular masses of between 27 33 kDa. These are proposed as being associated with sweating sickness immunodominance. PMID- 1923387 TI - Why dentists can't incorporate. PMID- 1923388 TI - Family trusts. PMID- 1923389 TI - Career navigation. PMID- 1923390 TI - Osseous and muscular changes after vertical ramus osteotomy. A magnetic resonance imaging study. AB - Magnetic resonance (MR) imaging was performed about 2 years after vertical ramus osteotomy of 10 patients to study changes in the mandibular condyle, cortical and cancellous bone of the proximal fragment, and muscles of mastication. MR imaging observations of the surgically treated patients were compared with findings in 10 asymptomatic untreated control subjects. The results showed that the MR appearance of bone marrow of the mandibular condyle was normal in all patients and in all control subjects. No MR evidence of avascular necrosis of the mandibular condyle was found. MR imaging artifacts from microscopic metallic particles were seen in all surgically treated regions. Thickening of the buccal and lingual cortical bone with narrowing of the bone marrow space was seen bilaterally in eight patients and unilaterally in two patients. Slight medial tipping of the mandibular condyle was seen unilaterally in two patients. Atrophic changes with decreased muscle volume and fatty replacement of muscle tissue was seen unilaterally in eight patients. None of these alterations were seen in the control subjects. MR imaging appears to be an excellent method to study morphologic changes of the muscles of mastication and osseous fragments after orthognathic surgery of the mandible. Thickening of the cortical bone and narrowing of the bone marrow space of the proximal fragment was frequently seen after vertical ramus osteotomy of the mandible and most likely represents remodeling associated with normal healing. PMID- 1923391 TI - Ultrathin arthroscope for use in the lower compartment of the temporomandibular joint. AB - Arthroscopy of the temporomandibular joint has been performed mainly in the upper joint space because the instruments available have been too thick to be safely inserted into the lower joint space. This article describes a newly developed ultrathin arthroscope with an outer diameter of 0.69 mm that has been specifically developed to be used in the lower space of the temporomandibular joint. This arthroscope can be inserted into the lower joint space with a standard 18-gauge needle. The article describes the arthroscope in its initial application to patient and cadaver material. PMID- 1923392 TI - Clinical follow-up study of third molar eruption from ages 20 to 26 years. AB - The development of 412 upper and lower third molars was clinically followed up for 6 years in 120 students, starting at the age of 20 years. Clinical and radiographic examinations carried out at baseline and 6 years later showed that during the follow-up period almost half the third molars originally recorded as partially erupted had erupted. When the lower third molars were initially invisible, only 9% of them had erupted by age 26 years whereas 29% remained invisible. When third molars had been already erupted at baseline, only a few were extracted during the 6-year follow-up period. It was concluded that a certain proportion of third molars erupt relatively late, and therefore the need for surgical interventions may decrease with age during early adulthood. PMID- 1923394 TI - Orthognathic surgery for mentally retarded patients. AB - The surgical treatment of mentally retarded children for esthetic reasons is discussed. In mentally retarded adults a facial deformity can give rise to functional problems; in some cases a facial deformity can stigmatize the mental state. In selected cases orthognathic surgery may offer a solution for either problem. Two cases are reported. PMID- 1923393 TI - Complications in the use of compression plates in the treatment of mandibular fractures. AB - The use of internal rigid fixation with plates in the treatment of facial fractures continues to increase in popularity. The principal advantage is in avoiding the use of maxillary mandibular fixation (intermaxillary fixation), thus enabling early return of function. However, there are clear guidelines for their use and technique of placement. A case is reported that demonstrates several avoidable complications in the use of compression plates and outlines the principles for the correct use of bone plates in mandibular fractures. PMID- 1923395 TI - Preoperative inventory of orthodontic appliances. PMID- 1923396 TI - Determining therapeutic efficacy in recurrent herpes labialis by lesion size analysis. AB - We devised an experimental model for the analysis of therapeutic efficacy of topical medications for recurrent herpes labialis with a double-blind, placebo controlled format. Rigid prestudy screening evaluations allowed the enrollment of a homogeneous starting population with characteristic herpetic reactivation in an early stage. Using precise measurements of lesion area for a 5-day period, we evaluated the effects of a novel medication containing tannic acid, which has demonstrated impressive inhibitory effects on herpes simplex virus in many recent studies, and salicylic acid, which has rapid absorption kinetics and substantial topical anti-inflammatory and keratin-disrupting properties. Using parametric and nonparametric tests, we studied differences in mean lesion size and used these measurements to evaluate objective and clinically applicable improvement criteria. Although there were no significant differences in mean lesion size at presentation (day 1) between the active medication and placebo groups, the former demonstrated significantly smaller lesions at days 2 through 5 (p less than 0.05). By day 5, 10 of 14 treated subjects showed improvement as defined by a 25% reduction in lesion size compared with day 1, in contrast to only 2 of 12 subjects in the placebo group (p = 0.0079, Fisher's Exact Test). This model can be employed in the evaluation of topical antiviral agents for herpes labialis in a healthy population, because it standardizes criteria for subject enrollment and provides objective and reproducible measurements of therapeutic efficacy. PMID- 1923397 TI - Therapeutic effects of daily or weekly chlorhexidine rinsing on oral health of a geriatric population. AB - The effects of a chlorhexidine rinse on salivary Streptococcus mutans, Lactobacillus, and Candida albicans counts and on periodontal conditions (gingival index, plaque index, pocket depths) were studied in 42 elderly subjects. Under supervision, they rinsed either daily or weekly for 6 weeks with a 0.12% chlorhexidine solution (Peridex). Saliva samples were taken for chemical and microbiologic examinations, and periodontal conditions were assessed at baseline, week 6, and 6 weeks after final rinse. Significantly lower S. mutans counts were found at week 6 for both rinsing groups (p less than 0.001). Lactobacillus and Candida counts were also generally lower at week 6, with the clearest improvement among persons with the highest counts of bacteria and yeast. Periodontal conditions were improved at week 6 (p less than 0.001) in both groups. Such improvements were not maintained 6 weeks after the rinsing regimen was completed. At baseline poor oral conditions were noticed, which placed most of the subjects at risk for tooth decay and periodontal disease. Without any other dental procedures but daily or weekly supervised rinsing, oral conditions were improved and this risk was reduced. Daily rinsing was not superior to weekly rinsing with 0.12% chlorhexidine. PMID- 1923398 TI - Clinical characteristics and management outcome in the burning mouth syndrome. An open study of 130 patients. AB - Clinical characteristics and treatment responses were studied in 130 patients with burning mouth syndrome (BMS). Most patients were postmenopausal women, and the tongue was the most frequently afflicted site. Although 39% of the patients complained of dry mouth, no causative factors were evident. Therefore BMS is assumed to be a functional disorder. This was at least partially confirmed because the most effective management was in response to mood-altering drugs. From our data BMS appears to be a chronic condition with variations in symptoms among patients and without a predictable endpoint. PMID- 1923399 TI - Pregnancy tumor: an analysis. AB - There is some disagreement about the validity of the clinical term "pregnancy tumor." On the basis of its clinical presentation and histologic appearance, some authors believe that it simply represents a pyogenic granuloma (PG), whereas others believe that the lesion is unique because of the apparent influence of female sex hormones. In an attempt to resolve this problem, a study was undertaken to determine whether a significant correlation exists between PG and pregnancy, and whether the clinical term applies to the other epulides. The study involved 42 epulides diagnosed clinically as pregnancy tumors. A chi-square analysis comparing 32 of these lesions with 757 epulides occurring in women revealed a significant disproportion in the number of PGs, whereas the number of peripheral ossifying fibromas and peripheral giant cell granulomas were within the expected range. Very few focal fibrous hyperplasias (fibromas) were diagnosed as pregnancy tumors. Clinical and behavioral features of pregnancy tumors diagnosed microscopically as PGs were also analyzed. The results indicated that the diagnosis of pregnancy tumor is valid clinically in describing a PG occurring in pregnancy, because it describes a distinct lesion not on the basis of histologic features but on etiology, biologic behavior, and treatment protocol. PMID- 1923400 TI - Histologic lesion in labial salivary glands of patients with systemic lupus erythematosus. AB - In an attempt to evaluate the presence or incidence of Sjogren's syndrome in patients with systemic lupus erythematosus (SLE), 72 randomly selected patients with SLE, regardless of sicca manifestations, underwent labial salivary gland biopsy. Thirty-seven patients (51%) had normal labial salivary gland tissue. Seventeen patients (24%) had a mild perivascular infiltration of 15 to 20 lymphocytes per focus. In the remaining 18 patients (25%) heavy infiltration of more than 50 lymphocytes per focus was observed. From the latter group five specimens showed perivascular distribution of the infiltrates. About 40% of patients with any infiltration had keratoconjunctivitis sicca. Patients with severe lymphocytic infiltration in minor salivary gland tissue rarely had kidney involvement and often had lymphadenopathy and circulating rheumatoid factor, cryoglobulins, and antibodies to SS-A (Ro) and SS-B (La) antigens. Vasculitis was not found more frequently in any group of patients. Our results suggest that perivascular lymphocytic infiltrates in the labial salivary glands of patients with SLE may be the initial histologic lesion of Sjogren's syndrome. PMID- 1923401 TI - Squamous cell carcinoma arising in residual odontogenic cyst. Report of a case and review of literature. AB - Odontogenic cysts are common pathologic lesions found in the oral and perioral structures. A case of squamous cell carcinoma arising within the lining of a large odontogenic cyst is described. Clinical and pathologic aspects of the previously reported cases are presented. PMID- 1923402 TI - Tooth length determination: a review. AB - Tooth length determination is a crucial step in endodontic treatment. Until the late 1970s, tooth length determination was based mainly on radiographic interpretation. The advent of apex locators, which identify the difference in the electrical resistance between the root canal and the periodontal membrane, ushered in a new era for measuring tooth length. However, the accuracy of these devices has been questioned. Pertinent literature is discussed with the aim of providing information on the development of the concept, techniques, and devices for tooth length determination. PMID- 1923403 TI - How to improve your chances of publishing your paper in the oral and maxillofacial radiology section. PMID- 1923404 TI - Radiologic changes in temporomandibular, hand, and foot joints of patients with rheumatoid arthritis. AB - Radiologic changes in the temporomandibular joint (TMJ) and in the joints of the hand and foot were recorded for 90 adult patients with rheumatoid arthritis. The severity of the changes was graded according to the Larsen classification of six grades (O to V), and mainly erosive changes were recorded. The assessment of the radiographs was performed with the aid of reference films. The radiologic changes in the TMJs corresponded to grade II (definite early abnormality) and paralleled those of most of the metacarpophalangeal and metatarsophalangeal joints. The most severe changes were localized to the wrists, with a median grade of III (moderate destructive abnormality). The severity of the changes was similar on the right and left sides of the TMJ. We conclude that TMJ involvement in patients with rheumatoid arthritis is severe and warrants a thorough initial clinical examination. Such a strategy will facilitate the diagnosis and treatment of TMJ changes in the early stages of the disease. PMID- 1923405 TI - Diagnosis of alveolar bone changes with digital subtraction images and conventional radiographs. An in vitro study. AB - The purpose of the present study was to compare the diagnostic properties of radiographs obtained with Ultra-Speed and Ektaspeed films when analyzed conventionally radiographs and after conversion in digital subtraction images. Artificial lesions, measuring 0.5, 0.7, 0.9, and 1.1 mm in diameter, were drilled in a dry skull with slow-speed burs. Standardized radiographs were obtained by means of acrylic bite blocks and a modification of the Rinn system. The results of this study demonstrated that sensitivity in the detection of the lesions was doubled after digitizing and displaying subtraction images compared with the conventional radiographic interpretation, independent of the use of Ektaspeed or Ultra-Speed films for the original radiographs. The diagnostic information seemed to be equal in radiographs obtained from Ultra-Speed and Ektaspeed films after digitization and image processing procedures. PMID- 1923406 TI - Optimum radiopacity of composite inlay materials and cements. AB - This study evaluated the radiopacity of recently introduced post-cured composite resin inlays and the composite dual-cure resin cements. Composite cement used as a luting material should have a minimal radiopacity of at least the same thickness as aluminum, to help in accurate radiologic discrimination. PMID- 1923407 TI - Bilateral dislocation of the temporomandibular joints. PMID- 1923408 TI - Stereoscopic evaluation of specimens (technical tip). PMID- 1923409 TI - Intranasal presentation of an intruded deciduous incisor. PMID- 1923410 TI - Postradiation dental extractions without hyperbaric oxygen. AB - This study examined the incidence of osteoradionecrosis after tooth extraction with low-epinephrine or epinephrine-free, nonlidocaine local anesthetics and conservative surgical techniques. Estimates of the absorbed radiation dose on irradiated alveolar bone were made by reviewing radiotherapy records. This investigation included 72 patients ranging in age from 22 to 80 years (median 57.4 years). We removed 449 teeth. Analysis of radiotherapy check films revealed that only 196 teeth (44%) were included within the treatment volume. The median prescribed tumor dose was 50 Gy (range 25 to 84 Gy) in 20 fractions (range 10 to 37), with a median dose per fraction of 2.5 Gy (range 1.88 to 3.14 Gy). Follow-up time ranged from 68 days to 19.3 years (median 4.8 years). No instances of osteoradionecrosis occurred as a result of dental extraction with this conservative method. PMID- 1923411 TI - Use of pressure-formed splints in oral surgery. AB - This article illustrates the scope of use for pressure-formed splints in two frequently encountered fields of oral surgery: maxillary segmental surgery and management of fractures of the mandible through the dental arch. The use of these splints in both fields allows significant modification of generally accepted procedures. PMID- 1923412 TI - Benefit of Bonefit implant system. AB - The International Team for Oral Implantology (ITI) Bonefit system has been introduced as an extended and improved system with respect to titanium plasma sprayed screws and the F-type implant. The clinical results of the Bonefit implant system were at least as good as those of the F-type implant. The Bonefit system, however, offers more indications and applications, especially in crowns and bridgework. Furthermore, the ITI Bonefit system appears to eliminate some of the reported shortcomings of the F-type implant. PMID- 1923413 TI - Facial fibrous dysplasia: report of a case. AB - A case of facial fibrous dysplasia that involved the left frontal, temporal, malar, and mandibular regions is reported. Conservative recontouring was done several times when the patient was 16 to 23 years of age. PMID- 1923414 TI - A simple method for fixation of mandibular fractures. AB - A useful but underused technique of mandibular fixation is described. Its main advantages over more traditional techniques are that it is easily and rapidly applied, suitable for both children and adults, and generally well tolerated. The method can be employed where only a few teeth are present and in displaced fractures together with an intraosseous buccal plate wire. It is a method that can be recommended for use in nonmaxillofacial units and in areas where only basic equipment and facilities are available. PMID- 1923415 TI - Oral Candida albicans in bone marrow transplant patients given chlorhexidine rinses: occurrence and susceptibilities to the agent. AB - The tongue and buccal mucosa of 26 bone marrow transplant recipients given three 0.12% chlorhexidine digluconate (CHX) oral rinses daily for 8 weeks were sampled weekly for oral Candida albicans. Putative C. albicans colony-forming units on selective bismuth sulfite glucose glycine yeast agar plates were identified with the API 20C system. The CHX minimum inhibitory concentrations (MICs) of oral C. albicans isolates obtained at all 8 sample weeks was determined with a microbroth dilution sensitivity assay. The CHX MIC range for yeast isolates selected randomly at all sample weeks was up to 2.5 to up to 20 micrograms/ml (mean MIC less than or equal to 8.5 micrograms/ml). The CHX MIC range for isolates at week 1 was less than or equal to 5 to less than or equal to 10 micrograms/ml (mean MIC less than or equal to 7.9 micrograms/ml) compared with less than or equal to 2.5 to less than or equal to 20 micrograms/ml at week 8 (mean MIC less than or equal to 8.8 micrograms/ml). Therefore the persistence of oral C. albicans in bone marrow transplant recipients using CHX rinses was due neither to low CHX susceptibilities nor to the development of resistance to the agent. PMID- 1923416 TI - Multivariate study of enterobacteria and Pseudomonas in saliva of patients with acute leukemia. AB - The effect of antibacterial treatment on the prevalence of gram-negative rods (enterobacteria and Pseudomonas) in the mouths of patients with leukemia was studied. Of the patients' salivary samples, 45% contained gram-negative rods compared with 12% in a control group of healthy persons. The antibacterial resistance patterns of gram-negative rods from healthy persons were different from those of the hospitalized patients. No relationship was found between the amount of antibacterial treatment and presence of gram-negative rods. The gram negative rods recovered from individual patients were usually not resistant to the antibacterial agents given to the patients in question. Only a few patients harbored the same clone of a gram-negative rod for a lengthy period. The resistance patterns of these clones of gram-negative rods were similar to those of gram-negative rods that were transient in the mouth. It was concluded that resistance to antibacterial agents is not a factor of major importance for the capacity of the gram-negative rods to become established in the mouths of hospitalized patients with leukemia. PMID- 1923417 TI - Periodontal attachment loss. PMID- 1923418 TI - Calcium blockers and gingival hyperplasia. PMID- 1923419 TI - Necrotizing sialometaplasia. A clinicopathologic study of sixty-nine cases and review of the literature. AB - The clinicopathologic findings in 69 cases of necrotizing sialometaplasia (NS) were analyzed and compared with 115 reported cases of NS in the English-language literature. Data comparing age, sex, race, location, clinical presentation, and possible predisposing factors are summarized. Analysis of the data indicates that NS can occur in a variety of clinical settings and may exhibit a spectrum of histologic features. Recognition of NS, regardless of its clinical or microscopic presentation, is essential to avoid inappropriate or unnecessary treatment for this benign reactive process. PMID- 1923420 TI - Evaluation of risk factors in smokeless tobacco-associated oral lesions. AB - Smokeless tobacco (ST) users and nonusers were recruited to evaluate the contribution of various risk factors (ST use, cigarettes, alcohol, and diet) in the development of oral mucosal lesions. Ninety-eight ST users with no lesion, 29 ST users with an oral lesion, and 33 nonusers were enrolled in the study. ST users with lesions, when compared with users with no lesion, were more likely to have used snuff than chewing tobacco (p = 0.01) and to have used more ST (p less than 0.01). Alcohol consumption, dietary intake of beta-carotene, and serum levels of beta-carotene were not related to an increased risk of lesion development. Our findings showed that the only significant risk factor for ST associated oral lesions was the extent of ST exposure. Of 127 ST users, 29 (22.8%) had an oral lesion at the time of examination. Of these lesions, 23 (79.3%) were hyperkeratotic and 6 (20.7%) were epithelial dysplasia. PMID- 1923421 TI - Case of atypical cyclopia. AB - A case of atypical cyclopia, involving the right eye with double lens, cornea, iris, and ciliary body, is reported. The possible mechanism of the histogenesis is discussed, together with a review of the relevant literature. PMID- 1923422 TI - Intraoral molluscum contagiosum. AB - Molluscum contagiosum (MC) presenting as a self-limiting disease of the skin is not uncommon. To date, however, documented cases of MC of the oral cavity have been rare. A case of MC of the palate of a 52-year-old man is reported. The clinical and histopathologic features of this uncommon oral lesion are discussed, and the literature is reviewed. PMID- 1923423 TI - Recurrent intraoral osseous choristoma. Report of a case. AB - The osseous choristoma of buccal soft tissue (intraoral soft tissue osteoma) is a rare entity that is reported not to recur after removal. A case involving the first documented recurrence of such a lesion is reported, and a review of the literature is presented. PMID- 1923424 TI - Radiographic interpretation of endodontic file length. AB - The purpose of this study was to evaluate the accuracy of examiners when asked to make file length adjustments with only a radiograph. The examiners viewed several radiographs under proper viewing conditions but without the aid of measuring devices. Two files of varying lengths (sizes 10 and 15) were placed in maxillary and mandibular premolars and molars from cadavers. The nine examiners were 67.91% in agreement of actual file length adjustment needed when adjustments of up to 0.5 mm were needed, 17.76% when adjustments of from 0.5 up to 1.0 mm were needed, and 14.33% when adjustments of greater than 1.0 mm were needed. PMID- 1923425 TI - Effect of preflaring on canal transportation. Evaluation of ultrasonic, sonic, and conventional techniques. AB - This study evaluated the effect on canal transportation when acrylic canals were preflared with Peeso reamers before the use of ultrasonic, sonic, and hand instrumentation techniques. Twenty resin blocks with simulated curved root canals were shaped with each technique to a size 40 file 0.5 mm from the apical foramen. Ten of the canals were preflared in the cervical region with No. 1 and No. 2 Peeso reamers before instrumentation; 10 canals that were not preflared served as controls. Transportation was measured on the inside canal curvature 3 mm from the canal orifice and 8 mm cervical to the working length, and on the outside canal curvature 1 mm cervical to the working length. Statistical analysis with Student's t test did not show a significant reduction in canal transportation for the preflared groups. In some areas the amount of transportation was less for the preflared groups; in other areas it was greater. PMID- 1923426 TI - Diffusion of medicaments within root canal dentin. A scanning electron microscopic study. AB - Root canals of 21 maxillary human teeth were enlarged with reamers and flushed alternatively with sodium hypochlorite and hydrogen peroxide. After its mechanical preparation, root canals were dressed with camphorated paramonochloropherol and/or formocresol delivered by paper points. All three medicaments crystallize both on dentin walls and inside dentinal tubules. The clinical implications of these findings are discussed. PMID- 1923427 TI - Increased horizontal angle of the mandibular condyle in abnormal temporomandibular joints. A magnetic resonance imaging study. AB - The horizontal condylar angle was measured in axial magnetic resonance images of normal and abnormal temporomandibular joints (TMJs). The average condylar angle in the normal joints was 21.2 degrees. In joints with disk displacement with reduction it was 29.7 degrees; joints with disk displacement without reduction, 33.5 degrees; and in joints with degenerative joint disease, 36.5 degrees. There were statistically significant differences between all four groups. Thus the condylar angle seemed to be increasingly larger with more advanced pathologic changes related to internal derangement and degenerative disease in the joint. The reason for the larger condylar angle in the abnormal joint was unclear. Joints with a larger condylar angle might have a greater tendency for internal derangement and degenerative joint disease to develop. Another possible explanation could be that remodeling associated with internal derangement and degenerative joint disease might result in a larger condylar angle. Further studies with longitudinal observations are needed to determine whether a causal relationship exists between the changes of the joint and a large condylar angle. PMID- 1923428 TI - Accuracy of measures of temporomandibular joint space and condylar position with three tomographic imaging techniques. AB - Fourteen temporomandibular joints in seven dry skulls, representing the distribution of horizontal and vertical condylar axis inclinations of a larger population, were imaged with three tomographic projection techniques. Closest anterior and posterior joint spaces were measured on radiographs, and sectioned plaster casts were made from impressions of actual joint space, Individualized horizontal and vertical correction of the condylar axis produced significantly more accurate (p less than 0.005) measures of condylar space than either standard 20-degree horizontal correction (SHC) or individualized horizontal correction (IHC) of the axis. Representations of joint space by SHC and IHC were not significantly different from each other. Numbers of uninterpretable images displayed a similar pattern of 9.5% for individualized horizontal and vertical correction, 14% for IHC, and 17% for SHC. This study supports the use of fully individualized condylar axis correction with temporomandibular joint tomography for increased accuracy of visualization of the osseous anatomy of the joint. PMID- 1923429 TI - Asymptomatic, radiologically detected chondrometaplasia in the temporomandibular joint. AB - Asymptomatic loose bodies were detected in the temporomandibular joint of a 62 year-old woman during an examination before comprehensive dental care. The radiologic interpretation was synovial chondrometaplasia (synovial osteochondromatosis). A histologic diagnosis was not obtained, because surgery was unwarranted in view of the lack of symptoms and the benign differential diagnosis. Review of the literature revealed 62 reported cases of temporomandibular joint chondrometaplasia, all of which included one or more of the following: swelling, pain, joint noise, and limited mandibular movement. These reports have described this entity as a rare lesion, but the rate of reports has increased, perhaps because of greater practitioner awareness and increased sensitivity of diagnostic tests. PMID- 1923430 TI - The posterior wall of the maxillary sinus as seen in panoramic radiography. AB - The dental and sinus projection programs of the PM 2002cc panoramic x-ray unit were compared with regard to the visualization of the maxillary sinus posterior wall of a dried skull. The posterior wall of the maxillary sinus appeared different on each program. In the sinus projection program the posterior wall appeared narrower than that in the dental projection program. The main cause for the difference of the maxillary sinus posterior wall image was the projection angle. In the sinus projection x-rays entered more tangentially to the posterior wall of the sinus than in the dental projection, but in the dental projection x rays entered more tangentially to the mediosuperior and medioinferior region of the maxillary sinus posterior wall. Thus a large, widely destructive lesion in the posterior wall of the maxillary sinus would be more easily detected with the sinus projection. On the other hand, lesions confined to the mediosuperior and medioinferior regions of the posterior wall will be depicted more clearly with the dental projection program. PMID- 1923431 TI - Automatic processing artifact. PMID- 1923432 TI - Missile localization in a gunshot wound victim. PMID- 1923433 TI - Retrospective analysis of low-velocity gunshot wounds to the mandible. AB - A retrospective study was conducted of 32 patients with mandibular fractures resulting from low-velocity gunshot injuries. Airway management was required in 25% of the patients, and 9% sustained major vessel injury. Patients were divided into two groups, depending on site of mandibular fracture: condyle, ramus, and coronoid (n = 10), and angle, body, and symphysis (n = 22). All patients in the condyle, ramus, coronoid group achieved clinical union without infection. Average postinjury maximal mandibular opening was restricted (28 mm), but the average follow-up period was relatively short (2 months). In the angle, body, symphysis group the infection rate was 27%, and in 18% of patients a continuity defect of the mandible developed. The average length of follow-up in this group was 5.4 months with a mean maximal mandibular opening of 36 mm. PMID- 1923434 TI - Occlusal contact area and temporomandibular joint symptoms. AB - A new method for quantitative occlusal measurement is presented. In this study occlusal contact areas in 79 patients with or without temporomandibular joint symptoms were assessed from the simple wax bite. The area of occlusion has showed no distinct differences between the two groups. The occlusal contacts did not show any significant correlations with temporomandibular joint dysfunctions. PMID- 1923435 TI - Severe bone resorption and osteoarthrosis after miniplate fixation of high condylar fractures. A clinical and radiologic study of thirteen patients. AB - Thirteen cases of high condylar fracture treated by open reduction and fixation with miniplates were monitored for an average of 18 months postoperatively. Satisfactory functional results were achieved clinically in all but one patient. Radiologically, however, signs of condylar resorption and osteoarthrosis were diagnosed in all patients. In four patients with associated multiple fractures of the facial bones, rapid complete resorption of the condyle was observed. These changes were markedly more severe than those observed in our previous study, in which osteosynthesis was performed by transosseous wiring and subsequent intermaxillary fixation for 3 to 7 weeks. Indications for rigid and nonrigid fixation in the surgical treatment of condylar fractures are discussed. PMID- 1923436 TI - Internal carotid artery thrombosis after blunt maxillofacial trauma. AB - Two cases of internal carotid artery thrombosis associated with a maxillary Le Fort III and mandibular angle fractures after maxillofacial blunt injuries are described. Both patients had delayed neurologic deficit and hemiparesis. The diagnosis was made by carotid angiography after clinical evidence of thromboembolism. Clinical aspects and etiology, with special attention to mechanism of injury, are discussed. PMID- 1923437 TI - Acute suppurative parotitis: a forgotten cause of upper airway obstruction. AB - A patient had threatened upper airway obstruction as a result of bilateral acute suppurative parotitis. Because of the rarity of this condition in recent times, accurate diagnosis was delayed and fiber-optic intubation in the intensive care unit was required to safeguard the airway. Management is described with reference to the surgical anatomy and previously reported cases. PMID- 1923438 TI - Pneumoparotid during dental treatment. AB - A rare case of pneumoparotid originating during dental treatment is reported. The condition should be considered in the differential diagnosis of acute parotid swellings. It is transient and does not usually require any treatment. PMID- 1923439 TI - Oral mucositis after bone marrow transplantation. A marker of treatment toxicity and predictor of hepatic veno-occlusive disease. AB - Oral mucositis and hepatic veno-occlusive disease (HVOD) are common complications after bone marrow transplantation (BMT). Forty-seven patients were prospectively examined for development of ulcerative oral mucositis (UOM) and HVOD after allogeneic BMT. In 17 patients (36%) UOM developed between 2 days before and 18 days after transplant (median 4 days after BMT). In seven patients (15%) HVOD developed with onset between 3 and 21 days after transplant (median 18 days after BMT). In a time-dependent analysis, in patients given busulfan plus cyclophosphamide or busulfan, etoposide, and cyclophosphamide UOM was 19 times more likely to develop than in patients treated by cyclophosphamide plus total body irradiation or by cyclophosphamide alone (p less than 0.001). Patients in whom UOM developed were 6.5 times more likely to develop HVOD than those in whom UOM did not develop (p less than 0.03). The sensitivity (86%), specificity (73%), and negative predictive value (97%) of UOM to predict HVOD were high, but the positive predictive value (35%) was low. The association of UOM and HVOD support the concept that both are toxic effects of treatment. Patients with hepatic abnormalities but without UOM are unlikely to have HVOD, and other causes of the hepatic dysfunction should be investigated. PMID- 1923440 TI - Effect of an antimicrobial mouthrinse on recurrent aphthous ulcerations. AB - Recurrent aphthous ulceration (RAU) remains a clinical problem for many patients. Efforts in prevention and/or treatment with prescription and nonprescription formulations have to date resulted in minimal success at best. A 6-month double blind clinical study of 96 adults compared a commercially available antimicrobial mouthrinse (Listerine Antiseptic [LA], Warner-Lambert Co., Morris Plains, N.J.) and a hydroalcoholic control to evaluate the effects of vigorous twice-daily rinsing on the incidence, duration, and severity of RAU in persons prone to this disorder. LA rinse and the hydroalcoholic rinse resulted in a statistically significant reduction in the incidence of RAU occurrences from baseline. The duration of lesions and the severity of pain in subjects with ulcers during the treatment period were also significantly reduced in the LA rinse group of patients when compared with baseline. The hydroalcoholic rinse did not show a significant effect versus baseline for either severity or duration of the lesions. Rinsing therefore can be of clinical value in reducing the occurrence of RAU in susceptible patients, and LA rinse can be of significant additional value in decreasing the duration and severity of RAU. PMID- 1923441 TI - Oral manifestations of paracoccidioidomycosis (South American blastomycosis). AB - Paracoccidioidomycosis (South American blastomycosis) is an uncommon, progressive systemic mycosis, potentially fatal if untreated. It is virtually restricted to persons spending time in Latin America. Reports of oral lesions are extremely rare in the English-language literature. Three adults with oral lesions as the first sign of paracoccidioidomycosis are described; this appears to be the largest series in the dental literature. The oral lesions had a characteristic appearance with a granular purpuric surface. The upper gingiva was a typical site, but lesions were also seen in the palate, tongue, and buccal mucosa. Two of the patients proved to have detectable pulmonary involvement. Long-term systemic ketoconazole therapy produced resolution of oral lesions in all cases. PMID- 1923442 TI - Management of cheilitis granulomatosa. AB - Peripheral facial nerve palsy, recurrent or persistent oral or facial swelling, and fissured tongue constitute a triad of symptoms known as Melkersson-Rosenthal syndrome. Granulomatous labial enlargement, known as cheilitis granulomatosa, is considered the single most important diagnostic feature of this syndrome. This lesion has been difficult to treat. This article describes a case of 8 months' duration of cheilitis granulomatosa of the lower lip, which was successfully managed with intralesional steroid injections. PMID- 1923443 TI - Simultaneous manifestation of Guillain-Barre and myofascial pain dysfunction syndromes. A case report. AB - Guillain-Barre syndrome is a neurologic disorder resulting primarily in muscle paralysis with possible mortality. Although several etiologic factors have been implicated, the cause of the disease remains unknown. This article reviews a case in which a patient was referred with of myofascial pain dysfunction syndrome with development of Guillain-Barre syndrome manifesting in the head and neck region. Diagnostic techniques and management are also discussed. PMID- 1923444 TI - Statistical observation of osteosarcoma of the maxillofacial region in Japan. Analysis of 114 Japanese cases reported between 1930 and 1989. AB - In Japan 114 cases of osteosarcoma of the maxillofacial region have been reported during the past 60 years. The average age at the onset of the disease in this region was about one or two decades later than that of osteosarcoma of other regions. Females were affected more frequently (59.6%) than males (40.4%). The mandible was more frequently affected (58.8%) than the maxilla (41.2%). Swelling was the conspicuous symptom for osteosarcoma of the maxillofacial region. Most patients received surgical treatment with or without radiation and chemotherapy; however, the prognosis is poor, regardless of the type of treatment. PMID- 1923445 TI - Pycnodysostosis. Report of a case and review of the Japanese literature, with emphasis on oral and maxillofacial findings. AB - We report a case of pycnodysostosis and review 54 cases of this syndrome in the Japanese literature, with special emphasis on oral and maxillofacial findings. Common findings were as follows: hypoplasia of maxilla and mandible, hypopneumatization of the maxillary sinuses, loss of mandibular angle, a grooved palate, and malpositioned teeth. PMID- 1923446 TI - Oral neurofibrosarcoma associated with neurofibromatosis type I. AB - One of the most feared complications of neurofibromatosis type I (NF-I) is development of cancer, which is estimated to occur in about 5% of cases. The most common associated malignancy is the neurofibrosarcoma (NFS). HOwever, oral NFS in association with NF-I has rarely been reported. We report two cases of oral NFS arising in patients with NF-I. Both patients died of their tumors. Oral NFS arising in association with NF-I appears to have an extremely poor prognosis, as do these tumors at other sites of the body. PMID- 1923447 TI - Endodontic therapy of traumatized incisors with crown and transverse intra alveolar root fractures. AB - A case involving traumatic injury to the maxillary anterior teeth with crown and transverse intra-alveolar root fractures is reported. The patient did not seek immediate treatment after trauma. Treatment included pulpectomy, fixation of a fractured root, root canal obturation, endodontic therapy of the coronal segment, and postoperative observation. Follow-up showed good results. Thus effective nonsurgical endodontic therapy of traumatized anterior teeth can result in a good prognosis in cases involving crown and intra-alveolar root fractures. PMID- 1923448 TI - Scanning electron microscopic study of odontoblasts and circumpulpal dentin in a human tooth. AB - Two combined scanning electron microscopic methods including modified fixative procedures were used for studying the morphologic aspects of the odontoblasts and the corresponding dentinal wall at different endodontic levels. The odontoblasts were tightly packed in the pulp horn, where they assumed pear-shaped profiles and, from crown to apex, successively looked spindle shaped, club shaped, and globular. Their number decreased in the pulp radicular portion, where the interglobular spaces were enlarged. The filling fibrillar material varied from crown to apex. A globular circumpulpal dentin was observed at all levels of the root canal. The tubule openings varied in number and size. PMID- 1923449 TI - Redundant shadows in rotational panoramic radiographs. Estimating the imaging positions of objects by mathematical analysis. AB - The sources of real, ghost, and double images in rotational panoramic radiographs generated by a machine with a continuous movement of the center of rotation are described. No assumptions are made with regard to the trajectory of the center of rotation; rather, an empirical approximation scheme is used to establish a regression from which measured positions of reference objects can be predicted. PMID- 1923450 TI - Floating teeth. PMID- 1923451 TI - Mandibular lesions in Gaucher disease. PMID- 1923452 TI - A response to "Can cytology proficiency testing programs discriminate between competent and incompetent practitioners?". PMID- 1923453 TI - From quality assurance to quality management in long term care. AB - This article describes the continuing evolution of the quality assurance program at Crown Nursing Home, a privately owned, skilled long-term care facility in Brooklyn, New York, into quality management. Activities are intended to improve the systems and processes of resident care, develop and implement practice guidelines, integrate suppliers and vendors into the facility processes, use information systems for indicator monitoring, encourage residents and family participation, provide care through a team approach, and promote human resource management and staff enhancement. PMID- 1923454 TI - A modeling framework for AIDS/HIV nonacute care services. AB - This paper describes the conceptual structure underlying the microcomputer-based modeling system developed by Mathematica Policy Research, Inc. The modeling system was developed to assist communities in planning nonacute care services for symptomatic human immunodeficiency virus (HIV)-infected persons. The modeling system is based on the assumptions that (1) the characteristics of the HIV epidemic and the availability of nonacute care service vary across communities and (2) combinations of nonacute care services can be appropriately substituted for one another and for hospital-based nonacute care to meet the varying medical and social needs of symptomatic HIV-infected persons. PMID- 1923455 TI - Integrating research activities, practice changes, and monitoring and evaluation: a model for academic health centers. AB - A study undertaken by the Joint Commission in 1986 proposed that some research activities at academic health centers (AHCs) be used to fulfill monitoring and evaluation requirements. This paper presents a framework for such use of research activities. To fulfill the monitoring and evaluation standards, AHCs and their medical staff departments must conduct planned and systematic quality assurance activities, and research and subsequent practice changes must be documented. In addition, particular research activities should correspond to the ten steps of the Joint Commission model of the monitoring and evaluation process. It is critical that research result in specific actions to improve care, along with follow-up monitoring and, when necessary, follow-up action. PMID- 1923456 TI - Peer review of social work documentation. AB - Peer review of social work documentation has helped promote the uniformity and consistency with which services are delivered; and social workers are exposed to the professional practice of their colleagues, since all staff members participate in conducting peer reviews. The system also helps identify areas of weakness or deficiency common to staff members. The detection of such patterns is the responsibility of the peer review committee, which brings them to the attention of the social work service management and of the service's QA committee. Corrective action is then taken to remedy identified problems. The system also has the potential to help identify patient problems and needs not met by the existing system of health care delivery; such gaps in service can then be brought to the attention of the management of the medical center for consideration and possible resolution. By focusing on documentation elements as indicators of high-quality and appropriate social work intervention, the peer review system used by the social work service has helped enhance social worker performance and service delivery. PMID- 1923457 TI - Therapy with mitoxantrone, ifosfamide, vindesine, and prednisolone for malignant lymphoma with adjustable doses and timing of courses. AB - Thirty-seven patients with malignant lymphoma were treated with mitoxantrone, ifosfamide, vindesine, and prednisolone. The time among courses was not fixed, being decided by the time for recovery from the leukopenia caused by the treatment. The drug dose was adjusted after the initial course. Of the 12 patients treated for the first time, eight had a complete remission and two had a partial response. Of the 18 patients who relapsed after another drug regimen, six had a complete remission and seven had a partial response. The SD of the leukocyte nadirs decreased after the first course, and time needed for recovery from leukopenia tended to shorten during treatment. Side effects seemed mild, and we can use many drugs safely in a short term without long drug-free intervals. Response rates were satisfactory, compared with other report, so this method of timing the start of courses with adjustment of the dose seems useful. PMID- 1923458 TI - Clinicopathological and histochemical studies of linitis plastica type gastric cancer with special reference to early gastric cancer in the region of the fundic gland. AB - In this study, early gastric cancer in the region of the fundic gland was found to occur predominantly in women. Many lesions of this type were identified in the posterior wall of the middle portion of the stomach. Histologically, the lesions were classified as poorly differentiated carcinomas in all cases of early cancer. On the other hand, in 9 patients with cancer of linitis plastica type having IIc lesions (less than 2.0 cm in diameter) located in the region of the fundic gland, the tumor focus was also in the posterior wall of the middle portion of the stomach. Giant folds were present diffusely in all other portions of the gastric mucosa in these latter cases. These cases also had diffuse infiltration of cancer cells into the submucosa, muscle layer and extraserosal regions. Histologically, the lesions were classified, in all cases of linitis plastica type, as poorly differentiated carcinomas including signet ring cells. Acid mucopolysaccharides (AMPS) and sialic acid were histochemically detected in the interstitial tissues of early gastric carcinomas and linitis plastica type gastric cancers. The AMPS digestion rates were higher for early cancer tissue. The present results support the hypothesis that early gastric cancer in the region of the fundic gland may occur in conditions favorable to tumor growth and may develop into cancer of linitis plastica type. PMID- 1923459 TI - Quantitative analysis of the cross-correlation between pattern ERG and pattern VEP. AB - The cross-correlation between PVEPs and PERG was investigated. (1) There were high correlations between PVEPs recorded from the inion and those from points Oz, Pz, Cz, and Fz in the range of 75-150 msec following pattern visual stimulation to the eyes although no correlation was found in the range 0-75 msec. (2) PVEPs recorded from the inion highly correlated with PERG in the 75-150 msec range but not in the 0-75 msec range. It suggests that the late negative component included in the PERG reflected the electrotonically spread at the eye level of PVEP. (3) Intra-individual reproducibility was studied. PVEPs showed a high reproducibility in the 75-150 msec range, but not in the 0-75 msec range. The reproducibility of PERG was high in the 0-75 msec range but also in the 75-150 msec range, where PERG reflected PVEPs. These results suggest that the early positive component of PERG was specific to the cell activities in the retina to the pattern visual stimulus, and had an origin different from the brain activity for PVEPs. PMID- 1923460 TI - Ca(2+)-dependent suppression of inwardly rectified K+ channels in rat basophilic leukemia cells. AB - A patch clamp technique was used in rat basophilic leukemia (RBL) cells to reveal the response properties of K+ Channels at different membrane potentials and the effects of Ca2+ on channel activity. In the whole-cell, cell-attached and inside out clamp configurations, inward K+ currents markedly increased with increasing hyperpolarization, showing the inwardly rectifying property of the currents. Mean amplitude of inward K+ currents was smaller with larger (1-10 microM) internal Ca2+ than with low (less than or equal to 100 nM) internal Ca2+, indicating that high concentrations of internal Ca2+ suppress channel activity. Single channel currents and the conductance of channels were not changed by high internal Ca2+ concentrations, but the open probability of the channels was decreased in these conditions. The results suggest that, by changing K+ channel activity, Ca2+ is a factor in the regulation of inwardly rectified K+ currents in RBL cells. PMID- 1923461 TI - A case of lead poisoning recovered by transposition of the work post. AB - A case of lead poisoning in a secondary lead refinery was reported. A 58 year old man working at the post of lead refining complained of severe lassitude and diarrhea. By increased urine coproporphyrin excretion, he was suspected of a case of lead poisoning. Clinical data from the health examinations revealed that he had been affected by lead. The patient was transposed to another work post where lead was not handled and rapidly recovered from the poisoning. PMID- 1923462 TI - [A new drug in a new role: dipyridamole in the treatment of HIV-1 infections?]. AB - Dipyridamole (DP) is a widely used coronary vasodilator and antithrombotic drug. The presented experiments demonstrate that DP inhibits the replication of HIV-1 and markedly potentiates the anti-HIV activity of azidothymidine (AZT) and dideoxycytidine in CD4-positive cells (monocyte-macrophages and T-lymphocytes). At the same time DP does not potentiate the bone marrow toxicity of AZT, and, in CEM-ss lymphoblastoid cells, it significantly suppresses the cytotoxicity of AZT. Studies on the mechanism of these effects suggest that DP inhibits the intracellular phosphorylation of physiological nucleosides, whereas it does not affect phosphorylation of AZT and other antiviral dideoxynucleoside drugs. This may lead to relative enhancement of the metabolic activation of dideoxynucleoside drugs and the inhibitory action of their active, triphosphate form on HIV reverse transcriptase. Studies comparing the binding of DP to proteins in tissue culture media and in human plasma suggest that in order to achieve significant antiviral potentiation in vivo, high doses of DP will be required. PMID- 1923463 TI - [Chronic gastritis and the presence of Helicobacter pylori in patients with non ulcerative dyspepsia]. AB - After definition in the group of the non ulcer dyspepsia (NUD) can be counted all those patients at whom beside the dyspeptical complaints, the radiological and endoscopical examinations didn't show ulcerative changes. The authors made biopsy 550 times on the occasion of 1390 gastroscopical examination (39.5% of the cases). The histological examination showed chronic gastritis in 372 cases (26.7% of all the examinations, 67.6% of the histological examinations). At this group of patients the dyspeptical complaints gave the principal indication of gastroscopical examination. Also it was examined the presence of dysplasia and intestinal metaplasia beside the different severity grade of chronic gastritis. The presence of Helicobacter pylori (Hp) was examined by histological methods. Hp positivity was noticed in 16.4% in the upper group. The authors made Hydrogen breath examinations in 34 cases between patients with NUD. The results of Hydrogen-breath examinations also raise the multifactorial nature of the NUD. On the basis of examinations chronic gastritis and CP infection can form subdivisions in the heterogenic group of patients with NUD. For exacter judgement of Hp pathogenicity are needed further and wide-spread examinations. The authors would like to call the attention to the indispensability of the biopsy during the gastroscopical examination. PMID- 1923464 TI - [Pathology of the collagen framework of the myocardium]. AB - The myocardial collagen matrix was studied in three groups of patients. The first group consisted of nine patients who had an isolated degradating damage of the collagen framework. In the second group the myocardial fibrillary matrix was examined in different cardiopathies. The author concluded that the collagen framework had degradated in the places of necroses and amyloid depositions, and it was bulky corresponding to fibrosis. Three persons who died suddenly in brain damages served as a control group. Integrity of the collagen matrix has an important role in the myocardial function, its desintegration--unrelated to myofiber necrosis--causes cardiac insufficiency. PMID- 1923465 TI - [Importance of pre- and post-natal ultrasonic examination in neonatal hydronephrosis]. AB - The widespread use of obstetric and neonatal sonography has resulted an increasing number of neonatal hydronephrosis, and some of them are asymptomatic. From November 1987 to May 1990 49 neonates with hydronephrosis or multicystic dysplastic kidney were seen. The most common conditions found were obstruction of the distal ureter (10), multicystic dysplatic kidney (12). Fifty-three percent of the cases were discovered on fetal screening during obstetric sonography, seven of them were asymptomatic at birth, but 4 of the asymptomatic babies underwent operation in the neonatal period. Nine of the postnatal diagnosed cases were incidental findings. The major benefit of prenatal echography is to allow early recognition of major uropathic conditions before postnatal infection worsens the prognosis. A correct postnatal ultrasound diagnosis was established in all cases. PMID- 1923466 TI - [Questions of medical responsibility]. PMID- 1923467 TI - [Experience with functional insulin therapy: metabolic follow up and patient cooperation]. AB - Functional insulin substitution, an insulin regimen made up of two daily injections of intermedier acting insulin and prandial boluses of regular insulin, was to be introduced in 49 type 1 diabetic patients, as previous regimens consisting of two or three daily injections proved to be inefficient due to the patients' lifestyle or inherent metabolic lability. 45 patients were treated with human insulin injected by NovoPen. In 38 cases therapy was changed in the frame of a one-week, small-group, inpatient, structured educational course. After a mean 14 months of follow-up metabolic status improved in 33 cases while there was further derangement in 16. 18 patients were practicing true functional therapy ie. doing blood glucose tests before each injection. Another 22 diabetics were trying to achieve better metabolic control through 2-3 daily blood glucose tests and insulin dose corrections. Metabolic status was not affected by the frequency of blood glucose testing, rather by the raising of the daily dose of Actrapid insulin in conjunction with the switch in therapy acting beneficially. All patients insisted on using NovoPen further on. PMID- 1923469 TI - [Therapeutic possibilities in the management of antitrypsin-deficient pulmonary emphysema]. AB - Congenital alpha-1-antitrypsin deficiency may lead to pulmonary emphysema in young adults. Authors review the therapeutic approaches of this disease. Attempts to augment the production of endogenous antitrypsin are discussed in detail. Possibilities of substitution by human alpha-1-antitrypsin and recombinant alpha 1-antitrypsin are summarized. Results with the use of specific elastase inhibitors as well as the role and the site of gen-therapy in treatment are reviewed. PMID- 1923468 TI - [Cytokine production in patients with systemic lupus erythematosus]. AB - The production of different cytokines, namely interleukin-2, interleukin-1 and tumor necrosis factor-alpha produced by peripheral immunocompetent cells was evaluated in patients with systemic lupus erythematosus in active and inactive stage of the disease. The results obtained were compared to healthy controls. It has been found that lymphocytes from both groups of SLE patients produced similarly less interleukin-2 activity. Interleukin-1 activity of monocytes was significantly reduced only in patients with active stage of the disease, whereas tumor necrosis factor-alpha production was diminished even in cases of inactive SLE. The simultaneous detection of the above mentioned cytokines may indicate further details concerning immunoregulatory disturbances of systemic lupus erythematosus. PMID- 1923470 TI - [Biological markers reflecting peripheral effects of thyroid hormones in autonomous thyroid adenoma]. AB - In some patients with functioning thyroid autonomous nodules preclinical hyperthyroidism is detected. It is important to know, whether in this intermediate clinical state beside the suppression of pituitary TSH secretion other target organs are also affected by serum free-thyroxine and free triiodothyronine levels still within the normal range. Determining some sensitive, but not specific biologic markers reflecting the impact of thyroid hormones at the peripheral tissue level, it was demonstrated that in the group of preclinical hyperthyroidism the mean level of plasma fibronectin exceeded that of the controls (mean +/- S. D.: 583.5 +/- 163.9 vs. 424.2 +/- 84.1 micrograms/ml, p less than 0.001), serum procollagen-III-peptide concentration was already significantly raised, though its value was still within the normal range (mean +/ S. D.: 0.73 +/- 0.17 vs. 0.57 +/- 0.16 U/ml, p less than 0.05), conversely, mean sex-hormone binding globulin level was the same as in euthyroid controls (mean +/ S. D. 47.4 +/- 18.2 vs. 48.3 +/- 16.3 nmol/l). The value of all three parameters was significantly elevated in patients with toxic nodular goiter. Based on the results of this study "tissue"-thyrotoxicosis is suspected in some patients with preclinical hyperthyroidism, which may have therapeutical implications. PMID- 1923472 TI - [Jozsef Jakab Plenck, Hungarian pioneer of dermatology]. PMID- 1923471 TI - [Lithium-induced chronic water-metabolism disorder (nephrogenic diabetes insipidus)]. AB - Lithium may induce all clinical physiological abnormalities of the polydipsia- polyuria syndrome. Authors describe a 61-year-old woman patient in whom permanent disturbance of the water metabolism, nephrogenic diabetes insipidus (NDI) was caused by lithium treatment, lasting longer than 10 years. The partial resistance of the fluid disturbance to vasopressin has been investigated by the administration of supramaximal doses of dDAVP. Considering the known antidiuretic effect of indomethacin, authors compared antidiuruetic activity of indomethacin and piroxicam (Hotemin) by studying standard parameters of water metabolism/free water clearance ect.) It was found that piroxicam, on mg basis a more effective antiinflammatory compound, was less antidiuretic then indomethacin. It was concluded, that there is no close parallelism between the structure and antiinflammatory and antidiuretic activity of nonsteroid antiinflammatory drugs. In the opinion of authors nonsteroid antiinflammatory drugs may have a role in the treatment of lithium-induced NDI, though, the establishment of the safety use of such therapy requires further studies. PMID- 1923473 TI - [Prevention of avoidable untimely death]. PMID- 1923475 TI - [Distribution of cells containing different IgG and IgA subclasses in the colonic mucosa in childhood ulcerative colitis and Crohn disease]. AB - The distribution of cells containing various subclasses of IgG and IgA were studied in the rectal and colonic mucosa from 14 paediatric patients with ulcerative colitis and four patients with Crohn's disease, as well as, from rectal biopsy specimens of 10 control subjects using monoclonal antibodies and the peroxidase method. The number of IgG3-containing cells in both the colonic and rectal mucosae of untreated patients with ulcerative colitis was significantly increased compared to controls. In the children with ulcerative colitis the number of IgG4 cells in the colonic mucosa was also significantly increased. In the rectal mucosa of patients with ulcerative colitis the percentage of IgG2 cells was decreased compared to the controls (22% versus 27%). In the great majority of specimens (in 37 out of 40) the number of IgA1 cells was higher than that of IgA2. The number of IgA1 cells in the rectal and colonic specimens of untreated patients with ulcerative colitis was slightly higher than that in the rectal specimens of controls. Authors speculate on the basis of their results that the observed IgG3 response in the patients with ulcerative colitis may be specific to the disease. PMID- 1923474 TI - [Thrombolysis by tissue plasminogen activator in acute myocardial infarct]. AB - The authors participated in the European multicenter investigation, ESPRIT, organized by the Wellcome Research Laboratories. Thrombolytic treatment by intravenous tissue plasminogen activator was performed in 25 patients with early (less than 6h) myocardial infarction. The efficacy of the treatment was controlled by repeat coronary arteriography at 60 minutes, at 90 minutes and at 24 hours of the tpA treatment. The infarct related artery was reperfused in 9/25 patients at 60 minutes, in 16/25 at 90 minutes and 17/18 at 24 hours. Four patients died after unsuccessful treatment or reocclusion. In two patients significant bleeding occurred at the puncture site but no transfusion was required. No other untoward effect was registered. The left ventricular function did not change significantly during the first day of infarction. It is concluded, that tpA is a safe thrombolytic agent in myocardial infarction. Its thrombolytic efficacy is similar to that of streptokinase. PMID- 1923476 TI - [Prevalence of severe visual impairement in school-age children in Hungary]. AB - The recorded prevalence of 6 to 14 year-old children with severe visual handicap was 0.43 per 1000 in Hungary, 1983/84. The territorial distribution showed significant difference in prevalences, the highest figures were found in two entities with three special institutions for severely visually handicapped children. Thus, the recorded figures are underascertained and the estimated rates are 0.52-0.60 and 0.21 per 1000 for children with severe visual handicap and, within it, blindness, respectively. PMID- 1923478 TI - [Family practice in the light of ophthalmology]. PMID- 1923477 TI - [Data on possibilities of rehabilitation of lower limb amputees]. AB - The authors investigated ways to improve the results of rehabilitation during the course of their clinical practice. During the last 2 years, amputation was performed on 136 patients and 50 patients were supplied with temporary protheses. 38 patients out of 50 answered the question form supplied. After analysis of the question form, the authors summarized the possibilities to improve the results of prolonged mobilisation and rehabilitation. This programme stresses the need for 1. early mobilisation-teaching to walk and 2. care of body and soul. PMID- 1923479 TI - [Current treatment of thoracic empyema in adults]. AB - Experiences obtained with 400 cases of thoracal empyema are described. The fact that the rate of lethality was 18.7% until present points out to the severity of the disease. The semi-conservative therapeutical methods used by the author (drainage, drainage and pleura lavage, pleura lavage and thoracoscopy, balance drainage) are presented. With their sensibly more frequent use the rate of operation could be reduced by 8% (from 36.5% to 28.5%) and the lethality rate by 7.6% (from 18.7% to 11.1). Further improvement of the results may be expected of the increased number of early detection (basic care), concentration of empyemic patients in special institutes (departments, wards) and due to it of a more efficient special treatment of uniform contemplation. PMID- 1923480 TI - [The effect of hemodialysis, using acetate and bicarbonate, on erythrocyte deformability]. AB - The red blood cell filtration parameters were examined in 82 patients with chronic renal failure and 50 healthy controls. The most expressed decrease in deformability was observed in uremic patients who had not been haemodialysed; the values nearest to the healthy ones were observed in transplanted patients. The deformability was considerably improved after haemodialysis, especially when acetate-containing dialyzing solution was applied. PMID- 1923481 TI - [Early cancer of the esophagus]. AB - The authors report four cases with the postoperative diagnosis of the early cancer of the esophagus. The histological type of the tumor was squamous cell carcinoma in three cases and adenocarcinoma in the remaining one. The tumors were localized in the lower part of the esophagus. Left sided thoraco-laparotomy was carried out in two cases. They used a right sided thoracotomy with abdominal and neck incisions. Trans-mediastinal esophagectomy was performed in the remaining one case. The continuity of the gastrointestinal tract was restored by substernal colon interposition in a case, by substernal stomach in another one and by oesophago-jejunostomy in the remaining two cases. New diagnostic possibilities and the international results of the treatment of the early esophageal cancer are discussed. PMID- 1923482 TI - [The role of antibodies in Graves' ophthalmopathy]. AB - The aim of this study was to investigate the possible pathogenetic role of autoantibodies to eye muscle membrane fractions in 75 patients with Graves' disease (50 patients with infiltrative ophthalmopathy). Autoantibodies directed to four fractions of human eye muscle--as well as thyroid membranes prepared by ultracentrifugation were detected by ELISA and Western blotting techniques. None of autoantibodies to various fractions of eye muscle membrane proved to be specific for Graves' ophthalmopathy, however, the presence of these antibodies and activity of eye symptoms were in correlation. Polyclonal autoantibodies to common epitopes on both thyroid and eye muscle membrane antigens (approximately 60 kD) were revealed that might be involved into pathogenesis of Graves' ophthalmopathy. PMID- 1923483 TI - [Fatal outcome of Kawasaki syndrome in a 4-week-old infant]. AB - A male infant at 4 weeks of age with features of Kawasaki disease is described who died at the end of the second week of his illness in consequence of serious pneumonia. The diagnosis was confirmed by laboratory tests and post mortem histological examinations. The latter showed systemic vasculitis without any changes of coronary arteries. PMID- 1923484 TI - [Dr. Jozsef Szenasy (1886-1951). (An overdue obituary)]. PMID- 1923485 TI - [Benefits of ecogenetics in Hungary]. AB - Five enzymes and one protein were studied in 10 ethnical and two reference groups involving 1370 persons. The frequency of atypical heterozygotes of plasma cholinesterase was 2.7%. Aldehyde dehydrogenase I isozyme deficiency was found in four persons including two gypsies. The low paraoxonase activity was found in 48.7% of persons examined. The proportion of gene frequencies of sigma-ALADH-1 and sigma-ALADH-2 in the locus of sigma-amino-levulinic acid dehydratase was 9:1. The percentage of slow acetylators was 56.9% in the total study sample. The rate of heterozygotes in Pi alleles of alpha 1-antitrypsin (protease-inhibitor) was 3.7% and one Pi ZZ phenotype could be observed. PMID- 1923486 TI - [Hungarian-made soya-based enteral nutrition solution in the artificial feeding of patients with pharyngo-laryngeal cancer]. AB - III.-IV. stage, protein-calorie malnourished, pharyngolaryngeal tumorous patients were artificially fed perioperatively. Protein source (soya-protein concentrate, TOFU-soya-protein-cottage cheese) manufactured in Hungary, was administered in enteral feeding through naso-gastric tube. The metabolism, transport and utility of the soya-based diet were investigated by biochemical methods and compared to the previously administered tube-feeding. The method is advised on the base of the favourable experiences of the authors. PMID- 1923487 TI - [Congestive gastropathy]. AB - 15 patients with congestive gastropathy were reported including clinical and pathological characteristics of the disease. Every patient had alcoholic liver cirrhosis and portal hypertension. 6 patient's stomach was resected while in 2 further cases the disease was found at autopsy. In additional 7 cases the characteristic microvascular changes were observed in endoscopic biopsy specimens from the gastric mucosa. The authors presume that this disease has an acute and a chronic stage. In the acute stage dilated capillaries are present under the surface, not related to the inflammation of gastric mucosa. This phenomenon was described in the literature. In the chronic stage there are dilated and tortuous vessels in the submucosal layer surrounded by collagenous connective tissue. The authors suppose that the thick and fibrotic submucosal layer causes microcirculatory disturbances in the gastric mucosa. The impaired microcirculation may cause extensive ulcers with profuse and sometimes lethal bleeding. PMID- 1923488 TI - [Family studies on the incidence of multiple pigmented naevi, familial skin melanoma and other malignant tumors]. AB - 102 family members of 14 patients with primary melanoma and multiple atypical pigmented naevi were investigated. Additionally to 14 patients with melanoma, 31 family members were found to have multiple atypical pigmented naevi. Most of them had light complexion and poor pigmentation capacity. A relative high frequency of malignant tumors other than melanoma were observed among blood relatives without multiple naevi. Members of melanoma-prone families need regular medical surveillance. PMID- 1923489 TI - [Sneddon syndrome (livedo and cerebrovascular lesion)]. AB - A typical syndrome going on with skin (livedo racemosa generalisata) and brain (ischemic vascular) involvement is presented. Symptoms of skin and nervous system are made known in detail, as well as possibility of early diagnosis and standpoint of treatment. PMID- 1923491 TI - [Let us get acquainted with the medical literature of the neighboring countries]. PMID- 1923490 TI - [Paying visits to our new colleagues at a new place of employment]. PMID- 1923492 TI - [The question of giant T inversion]. PMID- 1923493 TI - ["Curriculum pediatric and infant care"]. PMID- 1923494 TI - [Nursing congress 1991: basic values and new pathways]. PMID- 1923495 TI - [Basic values in nursing--how professional is our care?]. PMID- 1923497 TI - [The ideal nurse]. PMID- 1923496 TI - [The responsibility for the selection of nurses with regard to the requirements of the profession]. PMID- 1923498 TI - Localization of p62c-yes protein in mammalian neural tissues. AB - Expression of the c-yes proto-oncogene in mammalian brain, retina and adrenal gland was studied by immunohistochemistry and immune assays with affinity purified anti-yes IgG. Immunohistochemical staining with anti-yes IgG showed that in the central nervous system p62c-yes is highly expressed in mitral cells of the olfactory bulb, Purkinje cells of the cerebellum, hippocampal neurons and granule neurons of the dentate gyrus and ependymal cells lining central nervous system ventricles. Less intense labeling by anti-yes IgG was observed in most neuronal cell bodies in the brain. In addition, we observed intense c-yes immunoreactivity in the ganglion cells of the retina, the inner segment layer of rods and cones and medullary cells of the adrenal gland. Mapping p62c-yes expression to specific areas of mammalian neural tissues points to attractive experimental systems which could be used to investigate the function of the proto-oncogene product in neural processes. PMID- 1923499 TI - Phosphorylation and rapid turnover of hepatitis B virus X-protein expressed in HepG2 cells from a recombinant vaccinia virus. AB - The human hepatitis B viral (HBV) genome contains a conserved open reading frame known as the X-gene which is capable of encoding a polypeptide of 16.565 kDa. The corresponding protein has so far not been identified directly in HBV-infected cells, but in transient transfection assays the X-gene encodes a product that functions as a transcriptional transactivator. To characterize the subcellular distribution, stability and post-translational modifications of X-protein in human hepatoma HepG2 cells, we have established a vaccinia virus expression system. As the major X-gene product, a protein with an apparent molecular weight of 16 kDa, and reacting with an X-protein-specific antiserum, was expressed from recombinant vaccinia virus. In indirect immunofluorescence assay, X-protein appeared to be distributed throughout the cells, with a tendency to localize at the nuclear periphery and to accumulate in granules as its levels increased. By subcellular fractionation, we found about one-third of X-protein associated with the fraction defined as the nuclear framework. In pulse-chase experiments, X protein decayed with a bimodal half-life of 15 min and 3 h. X-protein having a half-life of about 15 min was found associated with the Triton X-100 detergent soluble fraction of HepG2 cells, while that associated with the insoluble fraction turned over more slowly. By metabolic labeling with [32P] orthophosphate, we show that X-protein is capable of being phosphorylated. Modification by phosphorylation could play an important role in the regulation of X-protein function. PMID- 1923500 TI - The MYCN protein of human neuroblastoma cells is phosphorylated by casein kinase II in the central region and at serine 367. AB - The MYCN gene has been implicated in certain neuronal tumours, such as neuroblastomas and retinoblastomas. These tumours express high levels of mRNA and protein of MYCN as a result of amplification. MYCN encodes a short-lived nuclear phosphoprotein whose function has not yet been elucidated. This study was undertaken to determine the pattern of MYCN protein (pMYCN) phosphorylation in human neuroblastoma cells. We report that pMYCN is phosphorylated in vitro by purified casein kinase II (CK-II). Two-dimensional phosphopeptide maps showed that most of the phosphopeptides of pMYCN phosphorylated in vitro by CK-II correspond to those phosphorylated in vivo. Fine mapping of the phosphorylation sites was performed using two synthetic MYCN peptides corresponding to pMYCN CK II consensus sequences. Both peptides were found to be phosphorylated by CK-II and competitively inhibited CK-II phosphorylation of pMYCN in vitro. Thus, we have localized two major CK-II phosphorylation sites in pMYCN, one to the highly acidic central region and the second to serine 367 proximal to the C-terminus. Our data demonstrate that pMYCN is a physiological substrate for CK-II and, since CK-II activity is stimulated in response to mitogens, CK-II phosphorylation of pMYCN may, therefore, represent one signal transduction pathway used by neuroblastoma cells. PMID- 1923501 TI - HTLV-1 Rex protein accumulates unspliced RNA in the nucleus as well as in cytoplasm. AB - The Rex protein of human T-cell leukemia viruses (HTLV) is a trans-acting regulator inducing the expression of gag and env mRNA containing the introns. The rex gene can also induce expression of unspliced RNA of human immunodeficiency viruses (HIV). We have analyzed the level of spliced and unspliced RNAs in nucleus and cytoplasm to understand the mechanism by which the Rex protein modulates RNA processing. With the gag gene of HTLV-1, the unspliced RNA was accumulated by Rex protein in both nucleus and cytoplasm. However, the apparent effects on nuclear unspliced RNA depended on the reporter genes: with the env gene of HTLV-1 as well as that of HIV-1, Rex did not accumulate the unspliced RNA in nucleus, but did so only in cytoplasm. These results clearly indicate that Rex protein not only activates the nuclear export of unspliced RNA, but also modulates some steps of RNA processing before the splicing, probably through stabilization of the precursor RNA. PMID- 1923502 TI - v-jun oncogene prevents terminal differentiation and suppresses muscle-specific gene expression in ASV-17-infected muscle cells. AB - Infection of replicating quail myoblasts with avian sarcoma virus 17 (ASV-17) results in the inhibition of terminal differentiation into multinucleated myotubes and in the acquisition of anchorage-independent proliferation. Expression of v-jun, the ASV-17 oncogene, concomitantly leads to the accumulation of the gag-jun polyprotein P65 in the nucleus and to the lack of expression of typical differentiation-specific genes such as myosin heavy chain (MHC) and alpha actinin. Surprisingly, expression of desmin, the muscle-specific subunit of intermediate filaments, is conserved in ASV-17-transformed myoblasts. Analysis of clonal strains of transformed myoblasts suggests that (i) suppression of morphological and biochemical differentiation depends on the absence of muscle specific gene transcripts; (ii) inhibition of muscle differentiation by v-jun does not depend on the transcriptional silencing of MyoD, a muscle-specific regulatory gene; (iii) expression of desmin is compatible with proliferation of ASV-17-transformed cells and is independent of v-jun and MyoD levels of expression. The present data suggest that nuclear localization of v-jun prevents terminal differentiation in myoblasts and selectively down-regulates muscle specific genes in terminally differentiated myotubes. In this respect, the behaviour of v-jun is quite different from that of v-myc, thus suggesting that these two oncogenes, although both encoding nuclear proteins, may have different mechanisms of action. PMID- 1923503 TI - Archival analysis of p53 genetic and protein alterations in Chinese esophageal cancer. AB - A strategy and methods for archival analysis of genetic and protein alterations in the p53 tumor-suppressor gene are presented. The tumor series includes 43 paraffin-embedded esophageal carcinomas from two high-incidence regions in the People's Republic of China. More than half contained elevated p53 protein levels which were detected by a high-titer polyclonal antiserum and a sensitive immunohistochemical method. To estimate the frequency of underlying mutations, DNA was isolated from conventional paraffin sections, amplified by the polymerase chain reaction, and examined by dideoxy termination sequencing. Analysis of exons 5-8 in a subset of 10 tumors revealed mis-sense point mutations in 4 out of 5 immunostain-positive tumors and a mutation encoding a stop codon in 1 of 5 immunostain-negative tumors. In this report of archival material, we conclude that detectable levels of p53 protein correlate closely with the occurrence of mis-sense mutations. Furthermore, these methods render large repositories of paraffin-embedded tumor and non-tumor tissues accessible to analysis. Immunohistochemical screening for elevated protein levels followed by sequence analysis represents an efficient strategy for the evaluation of the p53 mutational spectrum. PMID- 1923504 TI - Growth suppression of human breast cancer cells by the introduction of a wild type p53 gene. AB - Mutations in the p53 gene are associated with a wide variety of human tumors, including those of the breast. To assess functionally the role of the p53 gene in the development of human breast cancer, we introduced either wild-type or mutant p53 cDNA into three human breast cancer cell lines by DNA transfection. The cell lines MDA-MB 468 and T47 D contain only single mutated copies of the p53 gene, whereas the status of p53 in the breast cancer cell line MCF 7 remains equivocal. Following transfection, MCF 7 cells continued to grow unaffected both in vitro and in vivo in the presence of high levels of expression of the exogenous wild type p53 gene. In contrast, however, the continued expression of an exogenous wild-type p53 gene was incompatible with cellular growth in both the MDA-MB 468 and T47 D cell lines. Elevated levels of expression of the exogenous mutant p53 gene did not alter the growth of the cell lines in vitro. These data strongly suggest that the wild-type p53 gene can function as a suppressor of cellular growth in breast cancer cells. That the wild-type p53 gene does not suppress the growth of MCF 7 cells indicates that at least some human breast tumors can arise without functional inactivation of the p53 gene by mutation. These tumors may represent a separate prognostic group. PMID- 1923505 TI - Expression of wild-type p53 in human A673 cells suppresses tumorigenicity but not growth rate. AB - The p53 gene has been found to be mutated in many different kinds of human cancers. In a previous study, expression of exogenous wild-type p53 in human osteosarcoma cells by retrovirus-mediated gene transfer resulted in marked enlargement of cell size, reduced growth rate in culture and loss of tumorigenicity in nude mice. Here we examine the effects of expression of wild type or mutated p53 on human peripheral neuroepithelioma (PNET) A673 cells; these cells contained apparently normal alleles of the p53 gene but did not express a detectable quantity of p53 protein. Various characteristics of the p53-expressing cells were examined including morphology, growth rate, soft-agar colony formation, and tumorigenicity in nude mice. In contrast to osteosarcoma Saos-2 cells, expression of wild-type or mutant p53 protein in A673 cells had no effect on morphology or growth characteristics. However, clones expressing wild-type p53 protein had reduced ability to form colonies in soft agar and tumors in nude mice. To substantiate the genotype of wild-type p53-expressing cells, the proviral p53-encoding DNA of one cell clone was amplified by the polymerase chain reaction and sequenced. We concluded that expression of a single allele of the wild-type p53 gene was sufficient to suppress PNET A673 tumorigenicity but had no detectable effect on growth rate in culture. PMID- 1923506 TI - Analysis of viral and cellular gene expression during progression and suppression of the transformed phenotype in type 5 adenovirus-transformed rat embryo cells. AB - Transformation of secondary Sprague-Dawley rat embryo (RE) cells with type 5 adenovirus (Ad5) results in morphologically transformed cells which can undergo a series of sequential changes resulting in enhanced expression of the transformed phenotype, a process termed progression. Selection for a progressed phenotype often occurs after growth in agar or tumor formation in nude mice, and this process is reversible following treatment of cells with 5-azacytidine. In the present study we have analyzed a series of clonal populations of Ad5-transformed RE cells representing different stages in a defined progression lineage. Progression was not associated with alterations in the steady-state levels of mRNA produced by the viral transforming genes, E1A and E1B, or the cellular gene, c-myc. In addition, the tumor-promoting agent 12-O-tetradecanoyl-phorbol-13 acetate (TPA), which induces expression of a progressed phenotype in Ad5 transformed RE cells, did not significantly alter the RNA transcription rates of the Ad5 E1A or E1B genes, the TPA-inducible gene TPA-S1 or the TPA-responsive genes Pro1 or protein kinase C. TPA did, however, increase by 1 h the steady state level of c-fos mRNA, but this effect was similar in both progressed and unprogressed cells. Progression also did not involve a change in the RNA transcription rate of a number of cellular and viral genes, including actin, c-Ha ras, c-myc, v-fos, erbB, TGF-alpha, TGF-beta, Pro-2, transin, TPA-R1, v-myb and c mos, or other adenovirus genes in addition to E1A and E1B, including E2A and E4. Immunoblotting analysis using E1B polyclonal antiserum further indicated that progression was not associated with changes in the levels of an Mr 21,000 polypeptide encoded by E1B. Similarly, immunoprecipitation analysis with an Ad2 E1A monoclonal antibody indicated similar levels of the Mr 55,000 and 48,000 E1A polypeptides, as well as coprecipitated proteins of Mr 300,000, 107,000 and 105,000 [which is the retinoblastoma (Rb) protein], in E11 and E11-NMT cells. Immunoprecipitation of cell lysates with a monoclonal antibody specific for the Mr 105,000 Rb protein further demonstrated that progression also was not associated with a change in the level or state of phosphorylation of the Rb protein. However, transfection of a human Rb gene (also containing a neomycin resistance gene) into Ad5-transformed RE cells was more inhibitory, with respect to formation of G418-resistant colonies, in unprogressed than in progressed Ad5 transformed RE cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1923507 TI - Post-translational processing and subcellular localization of the Ras-related Rap2 protein. AB - The ras-related rap2 gene encodes a 21 kDa GTP-binding protein that exhibits many structural similarities with Ras proteins. In particular, it contains a C terminal CAAX sequence (C, cysteine; A, aliphatic residue; X, any amino acid) which has been shown to direct the post-translational modifications responsible for membrane binding of Ras proteins and nuclear lamins. We have generated cell lines overexpressing the Rap2 protein as well as specific anti-Rap2 antibodies and show that the protein is tightly associated with cellular membranes. Similarly to Ras proteins, the Rap2 protein is synthesized as a soluble and hydrophilic precursor that is processed to the mature hydrophobic membrane-bound form. During its maturation, the Rap2 protein is modified by the attachment of both palmitate and polyisoprenoid groups, as is also the case for H- and N-Ras proteins. Subcellular fractionation by sucrose density centrifugation as well as indirect immunofluorescence experiments show that the Rap2 protein is localized in a low-density compartment that morphologically overlaps with the endoplasmic reticulum, whereas Ras proteins are associated with the plasma membrane. In spite of similar post-translational modifications by palmitoylation and polyisoprenylation, Ras and Rap2 proteins are thus located on distinct subcellular structures. PMID- 1923508 TI - Characterization of the human N-ras promoter region. AB - Overexpression of ras proto-oncogenes has been implicated in cancer development. We therefore initiated a study of the human N-ras promoter to determine the regions that control N-ras expression and their potential for interaction with DNA-binding proteins. N-ras CAT constructs were stably integrated into K562 cells by electric field-mediated gene transfer in order to determine functional regions within the human N-ras promoter. A significant proportion of promoter activity was found to lie within a 439 bp fragment comprising an untranslated exon (exon 1) with the adjacent 5' sequence and a small CpG island. A 109 bp [corrected] fragment at the 5' end of exon 1 was essential for promoter activity, while a 45 bp [corrected] deletion from within this region decreased promoter activity by two-thirds. Unlike the human H-ras and mouse K-ras promoters, the N-ras promoter did not exhibit bidirectional activity. DNAse footprinting of the 439 bp fragment revealed seven protected regions, many of which contain sequences homologous to known DNA-binding protein sites (MLTF/myc, CREB/ATF, AP-1, AP-2, myb and E4TF1). In contrast, four putative Sp1 sites did not footprint. Using purified MLTF and appropriate competitors in gel shift and DNAase footprinting assays, we demonstrated binding of MLTF to the MLTF consensus sequence within exon 1. PMID- 1923509 TI - HeLaTG cells have mitochondrial DNA inserted into the c-myc oncogene. AB - To determine whether mitochondrial DNA (mtDNA) fragments found within the nucleus are transcribed, we have differentially screened a HeLaTG cDNA library. A clone that hybridized to mtDNA as well as to c-myc was identified. Analysis of the cDNA disclosed that it contained a mtDNA sequence, encoding cytochrome-c oxidase subunit III (coxIII) that was contiguous with and 5' of a c-myc sequence corresponding to part of exon 2 and exon 3. Hybridization of ScaI-digested DNA with a 1.05 kb c-myc probe revealed a unique band in HeLaTG cells, as well as a band common to HeLaTG and 13 other cell types examined. Solution hybridization of HeLaTG RNA with a radiolabeled, single-stranded cDNA probe containing the coxIII c-myc junction demonstrated a nuclease-resistant band that matched the full length of the junctional cDNA probe. A smaller band that equaled the size of the c-myc portion alone was also detected. Only the smaller band coinciding with the c-myc sequences was protected from nuclease digestion by RNA from other cells. When a radiolabeled probe synthesized in the opposite orientation was used, nuclease-resistant bands equal in length to the coxIII portion of the probe were detected after hybridization with RNA from all cells. These results indicate that insertion of mtDNA fragments into nuclear genes occurs and that subsequent transcription of a 'chimaeric' or 'fusion' mRNA containing both mitochondrial and nuclear sequences can ensue. PMID- 1923510 TI - Increase in specific DNA binding by carboxyl truncation suggests a mechanism for activation of Myb. AB - Oncogenic forms of the c-myb protein (Myb) often exhibit amino-terminal and/or carboxyl-terminal truncations. When the transcriptional activity of these proteins was examined it was found that carboxyl-truncated Myb is more effective as a transcriptional activator than full-length or amino-truncated Myb. In order to determine the effect of such truncations on sequence-specific DNA binding, we synthesized murine Myb in vitro and assessed DNA binding by using a mobility shift assay. Compared with the full-length protein no difference in binding was observed following deletion of the amino terminus, despite the removal of much of the first repeat of the DNA-binding domain. However, the specific DNA-binding capacity of carboxyl-truncated Myb was 4-6 times greater than that of the full length protein; moreover, DNA binding was independent of a 'leucine zipper' motif present in Myb. These observations suggest that the increased transforming and transactivating potential of carboxyl-truncated Myb is due, at least in part, to increased sequence-specific DNA binding. PMID- 1923511 TI - TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11). AB - We have cloned 70 kb of DNA from chromosome 11p13 at the site of a recurrent translocation in T-cell leukaemia (T-ALL): t(11;14)(p13;q11). The translocation involves the TCR-delta gene on 14q11 and a new site on 11p13. Two new and 10 previously identified translocations all mapped within 25 kb on 11p13, the 11p13 T-cell translocation cluster (11p13 ttc). A search for expressed sequences surrounding the breakpoint cluster region on 11p13 identified a gene telomeric of all breakpoints which is overexpressed in three T-ALL samples with a t(11;14). The gene T-cell translocation gene (TTG-2) encodes a small cysteine-rich protein. Forty-eight per cent of the amino acids are identical with another translocation deregulated gene, TTG-1 (T-cell translocation gene 1 or rhombotin) in 11p15. There are two copies of a cysteine-rich motif in both proteins. Two tandem copies of the same cysteine-rich motif are also present in the recently described lin 11, isl-1 and mec-3 gene products, and one motif is found in the CRIP protein. Therefore the proteins encoded by these two translocation-deregulated genes belong to this new class of cysteine-rich proteins with the 'LIM' motif, which are important in normal development. PMID- 1923512 TI - A c-myc gene variant without exon 1 and with an abnormal methylation pattern inherited in a woman with no evidence of malignancy. AB - A c-myc DNA with a deletion which includes 5' flanking, exon 1 and intron I sequences has been found in normal white blood cells of a mother and one daughter in a Northern Italian family. In addition, the degree of methylation of specific CCGG sites in the truncated DNA is lower in both mother and daughter than that found in normal DNA. It is of interest that deletions of the first exon and hypomethylation of the c-myc gene have usually been observed only in some neoplasias. However, our results demonstrate that the c-myc truncated DNA with the abnormal methylation pattern here reported is a genomic variant which by itself is not related to neoplastic transformation. PMID- 1923513 TI - Arg encodes a widely expressed 145 kDa protein-tyrosine kinase. AB - Arg encodes a protein highly related to the c-abl gene product with regard to overall structural architecture as well as the amino acid sequences of their tyrosine kinase, and src-homologous 2 and 3 domains. The two genes form a distinct subfamily of non-receptor tyrosine kinases and share a common homolog in Drosophila. In this study we characterized the arg protein product by expression of its coding sequence in bacteria. The recombinant arg protein was detected in bacterial lysates by immunoblotting and exhibited a molecular mass of 145 kDa. Phosphoamino acid analysis of the arg gene product following an immune complex autokinase reaction revealed tyrosine phosphorylation and established that it possesses tyrosine kinase activity. High-titer antibody capable of detecting the cellular arg gene product was generated by expressing a carboxy-terminal segment of arg in bacteria and using the recombinant protein as an immunogen. The arg gene product was identified in cultured human cells as a 145 kDa protein that exhibited autokinase activity. Analysis of arg expression in murine tissues revealed that arg, like c-abl, is widely expressed, further extending the similarities between the two genes, and suggesting that arg probably functions in signaling pathways fundamental to many cell types. PMID- 1923514 TI - Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. AB - In the murine interleukin 3 (IL-3)-dependent myeloid cell line 32D, down regulation of c-myc and ornithine decarboxylase (ODC) expression is an immediate response to IL-3 deprivation. This is followed by an accumulation of cells in the G1 phase of the cell cycle, and eventual cell death. However, clones of 32D cells harboring an expression vector which constitutively expresses murine c-myc did not down-regulate ODC transcripts in response to IL-3 withdrawal, and they failed to G1 arrest. Moreover, in contrast to control cultures in which the majority of death occurred following G1 arrest, c-myc clones rapidly initiated a program of cell death characteristic of apoptosis following IL-3 deprivation, and their subsequent loss of viability occurred with accelerated kinetics. The premature induction of apoptosis in cells harboring a deregulated c-myc gene suggests that apoptosis may be an important mechanism in the elimination of hematopoietic cells harboring mutations, such as constitutive c-myc expression, which imbalance normal cell cycle regulatory controls. PMID- 1923515 TI - Expression of MYB proteins in avian hematopoietic tissues. AB - MYB gene products are thought to be regulators of cellular replication and of differentiation. The major product of the avian MYB gene is a 75 kDa nuclear phosphoprotein which can activate transcription. A minor 89 kDa MYB protein of unknown function has also been described in murine and human cells. Additional heterogeneity at the level of MYB RNA which could affect the structure of MYB proteins has been described in several species. Such heterogeneity could explain the diverse effects of the MYB gene. To investigate the possible existence of heterogeneous and/or cell lineage-specific MYB proteins, five different avian hematopoietic tissues (bone marrow, bursa of Fabricius, embryonic spleen, thymus and yolk sac) were examined by immunoprecipitation with several MYB-specific antisera and SDS-PAGE analysis. In all five tissues there was a 75 kDa protein of uniform size which varied in abundance in a tissue-specific manner paralleling that observed for the 4.0 kb MYB RNA. A less abundant 89 kDa protein was also detected by several antisera in bone marrow, spleen, thymus and yolk sac but not in bursa. This 89 kDa MYB protein appears to be analogous to the 89 kDa MYB protein encoded by a minor but larger (360 nucleotides) MYB mRNA in murine and human cells. Immunoprecipitation of MYB proteins with an antiserum specific for exons 8 and 9 revealed a 74 kDa protein which co-precipitated and appeared to be complexed with p75 in normal hematopoietic cells and with the 48 kDa product of v myb in leukemic cells. PMID- 1923516 TI - Altered phosphorylation at specific sites confers a mutant phenotype to SV40 wild type large T antigen in a flat revertant of SV40-transformed cells. AB - The Rev2 cell line is a cellular revertant of the SV40 wild-type transformed rat cell line SV-52 [Bauer, M., Guhl, E., Graessmann, M. & Graessmann, A. (1987). J. Virol., 61, 1821-1827]. To characterize the level of cellular interference with the SV40 large T antigen (large T)-induced transformation pathway in Rev2 cells, we analysed the biological and biochemical properties of large T expressed in Rev2 cells. We found that Rev2 cells encoded an authentic wild-type large T, with regard to its sequence and its transforming functions. No differences were found in the metabolic stability of large T, or in complex formation with the cellular p53 protein, or in p53 metabolic stabilization. In contrast to SV-52 cells, Rev2 cells showed no association of large T with the chromatin fraction of isolated nuclei. This difference correlated with a reduced affinity of the Rev2 large T to SV40 DNA in vitro. The T proteins from both cell lines were phosphorylated at the same multiple sites. However, in Rev2 cells the phosphorylation of large T at specific serine -residues was significantly reduced. Thus the revertant phenotype of Rev2 cells may be due to an altered phosphorylation state of its large T protein, leading to altered nuclear localization and reduced transforming activity. The alterations of Rev2 large T properties and phosphorylation were very similar to the changes observed with mutant large T in FR(tsA58)A cells, an SV40 tsA58 N-type transformant, when the cells had reverted to the normal phenotype at the non-permissive growth temperature. Thus altered phosphorylation might provide a common structural basis for the biological inactivation of the large T proteins in these cells. PMID- 1923517 TI - Inhibition of jun transformation by a mutated fos gene: design of an anti oncogene. AB - The protein products of the fos and jun oncogenes (Fos and Jun) function as transcriptional regulators in the form of homo- or heterodimeric complexes that bind to DNA. Dimerization is mediated by a leucine zipper structure that serves to juxtapose alpha-helical regions of each protein, rich in basic amino acids, that form a bipartite DNA-binding domain. Although Fos participates exclusively in heterodimeric complexes, Jun can function either as a homodimer that has a low apparent affinity for DNA or as a more stable heterodimer with Fos that has a higher apparent affinity for DNA. We have used these properties of Fos and Jun to design a mutated fos gene, lacking a functional DNA-binding domain (supfos1), that suppresses the transforming activity of jun in trans. Here we show that chicken embryo fibroblasts transformed by jun revert to a normal phenotype after infection by a retroviral vector encoding supFos1. Furthermore, infection of normal cells with the supfos1 vector renders them resistant to subsequent transformation by jun. Inhibition of jun transformation was associated with the appearance of supFos1-Jun heterodimers and a reduction in the AP-1 DNA-binding activity contributed by Jun homodimers. These findings demonstrate that the function of leucine zipper-containing transcription factors can be investigated by the procedure of intracellular immunization. PMID- 1923518 TI - Synthetic HIV-1 Tat can dissociate HeLa nuclear protein-TAR RNA complexes in vitro: a novel Tat-nuclear protein interaction. AB - Multiple binding of Tat and nuclear protein(s) to HIV-1 TAR RNA appears to be essential for the Tat-mediated trans-activation. As synthetic Tat-(1-47), which lacks the basic domain and does not bind TAR RNA in vitro, efficiently transactivated HIV-1 LTR in HeLa nuclear extracts, we hypothesized that Tat might trans-activate by interaction with TAR RNA via a host nuclear protein. The role of nuclear proteins in Tat-TAR interaction was examined through evaluation of several synthetic Tat peptides for ability to bind TAR RNA in vitro both in the presence and in the absence of HeLa nuclear proteins. Our data show that both Tat (1-47) and Tat-(1-86) interact with TAR RNA-bound nuclear proteins, leading to dissociation of the nuclear protein-TAR RNA complexes; the N-terminal sequence of Tat appears to be involved in this interaction. Thus, after binding to TAR RNA, Tat can interact with a proximal TAR-bound nuclear protein and the resulting Tat nuclear protein complex, now displaced from TAR, may initiate a facile and rapid assembly of the RNA polymerase II transcription complex. This study thus recognizes a novel interaction between Tat and a nuclear protein(s). Here we propose that the interaction of Tat with a nuclear protein(s) occurring on TAR RNA may be one of several steps in the mechanism of Tat-mediated trans-activation of the HIV-1 LTR. PMID- 1923519 TI - Imbalanced expression of cellular nuclear oncogenes caused by v-sis/PDGF-2. AB - Two murine cell lines that overexpress v-sis/PDGF-2 were used to study the mechanism of cell transformation by SSV (simian sarcoma virus). In contrast to the parental cells that are phenotypically normal and serum-dependent for growth, v-sis-overexpressing cells grow in PDGF-free plasma medium, are unable to enter the G0 state and are highly tumorigenic. Analysis of the expression of some growth factor-induced early response genes in v-sis-overexpressing cells revealed: (a) high and constitutive c-myc mRNA levels in SSV-NRK cells; (b) unaltered levels of fra-1, fos B, jun B and krox 20 transcripts; (c) high and constitutive FOS staining due to c-FOS and FOS-related protein(s); (d) constitutive c-JUN and higher JUN D expression. These results are compatible with a model in which endogenous production of v-sis/PDGF-2 leads to deregulated expression of key cellular transregulators that, in turn, alter the cells' transcriptional program leading to the transformed state and malignancy. PMID- 1923520 TI - A human tumour-derived mutant p53 protein induces a p34cdc2 reversible growth arrest in fission yeast. AB - We have expressed wild-type and human tumour-derived mutant p53 cDNA genes in the fission yeast Schizosaccharomyces pombe. In the case of one mutant this resulted in a growth arrest of recipient yeast cells. In contrast, wild-type p53 and three other mutant proteins tested did not block outgrowth of colonies. Human and yeast cdc2 acted as functionally equivalent extragenic suppressors of the mutant induced growth arrest allowing the establishment of viable p53 expressor strains. In cotransformation assays the mutant allele was found to be dominant over wt p53. Our results provide the first evidence of a functional relationship between p53 and p34cdc2 in an in-vivo system and suggest that the wide variety of mutant proteins present in human tumours may fall into functionally distinct subclasses. PMID- 1923521 TI - Transformation by carboxyl-deleted Myb reflects increased transactivating capacity and disruption of a negative regulatory domain. AB - Carboxyl-truncated forms of the product of the c-myb proto-oncogene (Myb) are encoded by the v-myb oncogene, the rearranged c-myb genes of certain murine cell lines and a transforming recombinant c-myb retrovirus. We report here an examination of the abilities of a series of carboxyl deletions of Myb to transform hemopoietic cells. Increasing degrees of truncation resulted in increasing transforming capacity until the deletions removed the region responsible for transactivation by Myb. Because the effects of these deletions on transformation paralleled their previously described effects on the transactivating capacity of Myb but did not correlate with their ability to repress transcription, our results imply that removal of a domain which negatively regulates transactivation is responsible for oncogenic activation of carboxyl-truncated forms of Myb. Moreover, these data support the view that activated forms of myb transform by increasing and/or deregulating the expression of other genes. PMID- 1923522 TI - Differential expression of two types of the neurofibromatosis type 1 (NF1) gene transcripts related to neuronal differentiation. AB - A 360 residue region encoded by the neurofibromatosis type 1 (NF1) gene shows significant homology to the catalytic domains of both mammalian GTPase-activating proteins (GAP) and yeast IRA proteins. This GAP-related domain of the NF1 gene (NF1-GRD), like the GAP and IRA protein, has been reported to mediate hydrolysis of Ras-bound GTP to GDP, resulting in inactivation of Ras protein. In the present study, we identified two different types of NF1-GRD cDNA. One (type I) is identical to the previously reported sequence, and the other (type II) contained an additional 63 bp insertion that encodes for a region of 21 amino acids in the center of the NF1-GRD molecule. Alternative splicing is the most likely mechanism by which these two types of transcripts arise. Our observations reveal that the type I transcript is predominantly expressed in undifferentiated cells, whereas the type II transcript predominates in differentiated cells. Furthermore, the expression pattern of type I and type II NF1-GRD mRNA immediately changed in SH SY5Y neuroblastoma cells when neuronal differentiation programs were induced by retinoic acid treatment. We propose that the differential expression of type I and type II NF1-GRD transcripts might be an 'on/off' switch that regulates the catalytic activity of the NF1 gene product, which plays an important role in the regulation of neuronal differentiation. PMID- 1923523 TI - Characterization of the promoter region of the c-yes proto-oncogene: the importance of the GC boxes on its promoter activity. AB - In this study we cloned the 5' flanking sequence of the human c-yes gene and identified its promoter region. A 0.53 kilobase pair (kbp) fragment containing the 5' terminus of the c-yes gene showed strong promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and transfected into monkey CV-1 cells. By nuclease S1 mapping multiple transcriptional start sites were detected within the promoter region. Nucleotide sequence analysis revealed that the c-yes promoter region had high G + C contents (64%) and contained six GC box-like sequences (one at the 5' distal region and five in a cluster at the 5' proximal region), but not a TATA box. These features of the c-yes promoter region are similar to those of other protooncogenes, ras family genes and c-raf-1, and some house-keeping genes. Deletion analysis suggested that the most downstream 0.21 kbp region is primarily important for the promoter activity. This 0.21 kbp region contains one major and another minor transcriptional start site. Five GC box-like sequences were located within this region, and four of them were shown to bind with purified Sp1 transcription factor. Furthermore, using the base-substituted mutants of the Sp1-binding sites, each GC box in the cluster (GC1 to GC4) was shown to affect the c-yes gene expression. PMID- 1923525 TI - Essential AP-1 and PEA3 binding elements in the human urokinase enhancer display cell type-specific activity. AB - We have characterized a transcriptional enhancer of the human urokinase-type plasminogen activator (uPA) gene in three transformed human cell lines: HeLa, HepG2 and HT1080. The enhancer is located approximately 2 kbp upstream of the mRNA cap site and is active in all three cell lines. By footprinting and gel retardation analysis we found that it contained two binding sites for transcription factor AP-1, encoded by the fos and jun proto-oncogene families. The most upstream of these sites was juxtaposed to a binding site for PEA3, a product of the ets/Spi proto-oncogene family. By transient transfection analysis of deletions, point mutations and subcloned fragments, we found these sites to be crucial for enhancer activity. However, the sites displayed differences in activity in the three different cell lines. The downstream AP-1 site was almost exclusively responsible for enhancer activity in HeLa cells, whereas the AP 1/PEA3 site played a major role in HT1080 and HepG2 cells. The implications of our findings for the known regulation of uPA expression by transforming oncogenes, adenovirus E1A protein and glucocorticoids are discussed. PMID- 1923524 TI - Mouse bcl-3: cDNA structure, mapping and stage-dependent expression in B lymphocytes. AB - Human B-cell chronic lymphocytic leukemias (CLLs) are malignancies of mature B lymphocytes. A subset of these tumors is associated with a non-random t(14; 19) translocation (Ueshima et al., 1985). Recently a gene (bcl-3) has been identified in the region adjacent to the chromosome 19 breakpoint in this translocation (McKeithan et al., 1987; Ohno et al., 1990). We now report the isolation of cDNA clones of mouse bcl-3. The mouse bcl-3-coding region is 1746 bp long and exhibits 80% identity with human bcl-3 at both the nucleotide and amino acid level. The bcl-3 locus maps to the proximal end of mouse chromosome 7, which is syntenic to human chromosome 19. The bcl-3 probe readily detects particularly abundant amounts of a 1.8 kb mRNA in mouse tumors consisting of follicular center mature B cells and large pre-B cells, but not in small pre-B cells. The bcl-3 pattern of expression is distinctive in the spectrum of B-cell maturation in that bcl-3 transcripts are particularly abundant in B-cell lines immortalized just prior to Ig switch. The bcl-3 pattern of expression also bears close resemblance to that of bcl-2 (Gurfinkel et al., 1987), which is frequently associated with human B follicular lymphomas [t(14; 18)] and some chronic lymphocytic leukemias (Adachi et al., 1989; 1990; Adachi & Tsujimoto, 1989). PMID- 1923526 TI - Frequent p53 mutations in chemically induced murine fibrosarcoma. AB - Patterns of p53 expression were investigated in chemically induced fibrosarcoma tumors and cell lines. Most, if not all, cell lines were found to carry alterations at the protein level, reflected in the overproduction of greatly stabilized p53 proteins. In many cases, this was accompanied by formation of complexes with hsc70. Hence, all of these lines may be expressing one sort or another of mutant p53. The mutant nature of the p53 gene was directly verified, in a number of cases, by PCR-amplified cDNA cloning. In one line, no p53 protein was made at all; this turned out to be because of a mutation in a splice donor site, resulting in the production of an aberrant mRNA. In all other cases, mRNAs carrying mis-sense mutations were present, and were sometimes expressed along with wt p53 mRNA. When tested in an in vitro transformation assay, all cloned mutants possessed a discrete oncogenic activity, while having lost the ability to interfere with oncogene-mediated transformation. The system described here could potentially be very helpful in elucidating the significance of p53 mutations. PMID- 1923527 TI - Viral Ha-ras mediated mammary tumor progression. AB - An immortal mammary epithelial cell line, Comma 1D, and primary cultures of mammary epithelial cells were used to examine the effects of vHa-ras on mammary tumor development. In culture, Comma 1D and primary cells were morphologically indistinguishable. Infection with a replication defective vHa-ras retroviral vector (psi ras) did not alter their in vitro phenotype. Uninfected Comma 1D cells implanted into gland-cleared mammary fat pads gave rise to dysplastic outgrowths, while implants of primary cells gave rise to normal gland structures. After psi ras infection, implants of Comma 1D cells progressed to adenocarcinomas and those of primary cells resulted in initiated dysplastic outgrowths. High level infection of either cell type with replication competent HaMSV (psi ras plus helper virus) resulted in in vitro transformation and undifferentiated in vivo tumors. Thus, in vivo analysis was necessary to detect the observed correlation between tumorigenic stage and level of infection. In this system, expression of vHa-ras was vital but not sufficient for mammary tumor initiation and progression, which resulted from an accumulation of events that did not need to occur in a specific order. PMID- 1923528 TI - Activated Val-12 ras p21 in cell culture fluids and mouse plasma. AB - Activation of ras oncogenes has been associated with a variety of cancers as well as their precursor lesions. Ras proteins activated by substitutions at amino acid positions 12, 13 or 61 have not been identified in normal tissues and therefore their detection may have clinical value. In this study our objective was to determine whether activated ras proteins could be released into the extracellular environment. To test this hypothesis, we used ras-transformed NIH3T3 cells that express an activated p21 containing valine (Val-12 p21) at position 12 instead of the normal glycine (Gly-12 p21) and a monoclonal antibody (mAb) designated DWP that is specific for the activated Val-12 ras proteins. Culture fluids collected from NIH3T3 cells transformed by the activated Val-12 p21 were shown, using mAb DWP in a sandwich ELISA format, to contain the activated Val-12 p21. In contrast, culture fluids from non-Val-12-containing cells were unreactive with mAb DWP. PSV LM-EJ cells which overexpress the activated Val-12 p21 were injected subcutaneously (SQ) into nude mice to produce tumors. At the time of gross tumor appearance (14-21 days after tumor cell inoculation), plasma was collected from the PSV-LM-EJ tumor-bearing mice as well as from a series of control mice. Employing mAb DWP as a detection reagent in the sandwich ELISA format, we were able to detect the Val-12 p21 in the plasma of the PSV-LM-EJ tumor-bearing mice. Activated Val-12 p21 was not present in the plasma of non-tumor-bearing mice, or in the plasma of mice bearing SQ tumors composed of non-Val-12 p21 ras transformed cells. This report is the first description of an activated ras protein (Val-12 p21) in the plasma of tumor-bearing mice and demonstrates that the results of the Val-12 p21-specific ELISA could be validated with Western blot format. PMID- 1923529 TI - The chicken junD gene and its product. AB - We have isolated and characterized the chicken junD gene. It does not contain an intron; its upstream regulatory sequences lack the AP-1-binding site seen in c jun but include two CRE elements. Downstream untranslated sequences do not show the destabilizing signal ATTTA. The amino acid sequence of the chicken JunD protein is closely related to that of mouse JunD in the dimerization and DNA contact surfaces of the carboxy-terminal region; additional homologies to mouse JunD are seen in acidic and amphipathic amino-terminal domains. Chicken JunD contains stretches of oligoglycines, alanines and prolines, possibly acting as hinges that connect functionally distinct domains of the protein. Chicken junD is broadly expressed at low basal levels in differentiated tissues and at somewhat higher levels in cultured fibroblasts. The cDNA clone of junD was transcribed and translated in vitro. The resulting JunD protein migrates in between 40 and 50 kDa in an SDS gel and can be precipitated with an antibody prepared against a polypeptide consisting of the carboxy-terminal 100 amino acids of mouse c-Jun. PMID- 1923530 TI - Mutant p53 detected in a majority of Burkitt lymphoma cell lines by monoclonal antibody PAb240. AB - The status of the p53 gene in lymphoblastoid cell lines (LCLs) and Burkitt lymphoma cell lines (BLs) was investigated. Southern blot analysis demonstrated that no major deletions or rearrangements had occurred in the p53 gene in any of the cell lines. The p53 protein was examined by immunoprecipitation using two monoclonal anti-p53 antibodies. PAb1801 recognizes both wild-type and mutant p53. PAb240 reacts exclusively with mutant p53. Fourteen LCLs reacted with PAb1801, but not with PAb240, suggesting that none of them expressed mutant p53. However, one LCL had mutant p53. This LCL differs from other LCLs in that it grows to higher cell densities and has a higher agarose clonability. All BLs expressed p53. Out of 15 BLs, nine (60%) carried mutant p53, as indicated by their reactivity with PAb240. Among the nine BLs with mutant p53, eight Epstein-Barr virus (EBV)-positive. Three out of the six BLs with wild-type p53 were EBV positive. Multiple EBV-converted sublines all exhibited the same p53 status as the parental line. Our results indicate that the p53 gene is mutated in a majority of Burkitt lymphoma cell lines (BLs), and suggest that p53 mutation contributes to the malignant phenotype of these cell lines. PMID- 1923531 TI - Detection of transforming genes by transfection of DNA from primary soft-tissue tumours. AB - A series of adult soft-tissue tumours were screened for the presence of activated oncogenes by transfecting tumour DNA into NIH3T3 mouse fibroblasts. In these studies an activated K-ras gene that contained a mutation at the second position of codon 12 (GGT----GAT) was found in a leiomyosarcoma. In addition, following transfection of DNA from a liposarcoma, we identified an activated gene that failed to hybridize to probes prepared from 10 known human oncogenes (K-ras, H ras, N-ras, ret, met, trk, mas, dbl, raf and hst) that have previously been detected in DNA transfection experiments. BamHI-BamHI fragments of this activated gene of 3.5 and 8.5 kb were cloned from NIH3T3 secondary transfectants using a probe that detects the human alu family of highly repetitive DNA sequences. Repeat-free subclones of these BamHI fragments were used to map this gene to human chromosome 19 (p13.2-q13.3). Our studies also demonstrate that a subclone from one of the BamHI fragments detects a 3.0 kb transcript in primary and secondary transfectants. PMID- 1923532 TI - p53 mutations in ovarian cancer: a late event? AB - Using a combination of polymerase chain reaction and single-strand conformation polymorphism techniques we analyzed 34 ovarian cancer samples (30 primary tumors and four matched metastases) for the presence of mutations in exons 5, 6, 7, 8 and 9 of the p53 gene. Mutations in this portion of the gene are known to lead to the loss of the oncosuppressive potential of p53. Thirty-six percent (11/30) of the ovarian carcinomas tested presented a mutated p53 allele. Mutations were clustered in exons 5 and 7 to the exclusion of the other exons screened. Most mutations (10/11) were point mutations, but no preferential pattern of nucleotide substitution could be observed. In three tumors the mutation of one allele was concomitant with the loss of the wild-type counterpart. Another sample presented both alleles independently mutated. These observations are in agreement with the recessive nature of the p53 mutation. However, analysis of tissue sections from two tumors showed that the portion composed of 100% cancer cells could hold both the mutated and the wild-type form. Moreover analysis of serial sections gave evidence of a heterogeneous cellular content in one of these tumors, suggesting that p53 mutations may, in some cases, occur late during ovarian cancer evolution. It is, moreover, noticeable that, in matched sets of primary tumors and metastases, the same mutation was observed in both tumor samples. Therefore, even as a late event, p53 mutation occurs before metastatic spread. PMID- 1923533 TI - Polymorphism at codon 213 within the p53 gene. AB - This report describes a rare polymorphism at codon 213 (silent alteration of CGA to CGG) within the coding region of the p53 gene. The rare polymorphic allele was present in six cases out of 189 lung and breast cancer DNAs analyzed (3.2%) and resulted in the loss of a TaqI site. This allele could be mistaken for a mutation when screening methods of mutation analysis are used without comparison with normal tissue DNA. PMID- 1923535 TI - Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. AB - Accumulation of the p53 protein was analysed in 212 human malignant lesions. Immunohistochemical staining with new polyclonal (CM-1) and monoclonal antibodies (BP 53-12 and BP53-24) to p53 on methacarn-fixed paraffin sections showed positive staining in 161 (76%). The positive tumours were found across a wide range of human malignancies including breast, colon, stomach, bladder and testis carcinomas, soft-tissue sarcomas and melanomas. The staining was always confined to the malignant lesion. Immunoprecipitation and quantitative ELISA assays established that the positive staining was associated with accumulation of the protein and that the protein was frequently in a mutant conformation. Accumulation of mutant p53 protein is therefore a common feature of human malignant disease. PMID- 1923534 TI - Mutation of the p53 gene in a differentiated human thyroid carcinoma cell line, but not in primary thyroid tumours. AB - The p53 gene has been implicated as a tumour suppressor, with mutations occurring in many carcinomas, such as colon, breast and lung. We have sequenced exons 5, 7 and 8 containing conserved gene regions in the only available differentiated thyroid follicular carcinoma cell line and found a mutation at position 273, Arg- --His, with no normal allele present. The same mutation was also present in DNA from the tumour of origin. However immunohistochemical analysis of 129 human thyroid tumours using a panel of p53 antibodies was unequivocally negative. Southern blotting in 20 cases failed to demonstrate any deletion or rearrangement, and direct genomic sequencing of 20 carcinomas showed normal DNA sequence for exons 5, 7 and 8. Thus p53 abnormalities may not be important in human thyroid carcinogenesis, in contrast to colon, breast and lung. However, the FTC 133 cell line was only established after 132 unsuccessful attempts with other differentiated thyroid follicular tumours. Since this line and the corresponding tumour of origin have a p53 mutation, we propose that p53 mutation may confer on thyroid follicular tumour cells the ability to grow in culture. This has potential applications for the future development of thyroid carcinoma cell lines. PMID- 1923536 TI - Change of specialty status initiated. PMID- 1923537 TI - Mercer County contingent urges physician action. PMID- 1923539 TI - Massachusetts Medical Society studies potential. PMID- 1923538 TI - Assisting physicians in decision-making. AB - The American Medical Association's long-standing commitment to improving the quality of medical care has been marked by a variety of efforts, from improvement of medical education and accreditation to technology assessment and peer review. But with increasing nationwide attention on evaluating quality of care, the AMA, as well as many other physician organizations, has focused on developing practice parameters that identify appropriate medical care. PMID- 1923540 TI - The new strategy and peer review. PMID- 1923541 TI - Liability insurance impact uncertain. AB - Practice parameters are here to stay and will have, in fact already have had, a dramatic effect upon the practice of medicine. The effect of practice parameters upon professional liability and professional liability carriers is uncertain. PMID- 1923542 TI - New fee schedule tests staff skills. The Health Care Group. AB - The Medicare Fee Schedule (MFS) picture is quite incomplete, with myriad details unsettled. But one thing is clear: the shift to a new reimbursement system is loaded with significant practice management implications and challenges. Now, before the MFS is implemented, physicians should evaluate their management operations and business systems, to meet the challenges ahead. Most physicians understand that practice viability will depend on increasing their patient base and the scope of services delivered to non-Medicare patients. Yet many do not understand the marketing and management challenges implied in such growth. The issues are these: how can a practice attract more non-Medicare patients? And how can such growth be accommodated without disproportionately increasing costs or inconveniencing patients and staff? PMID- 1923543 TI - Who's to blame? PMID- 1923544 TI - Criteria for chronic fatigue syndrome. PMID- 1923545 TI - Emergency physicians work on image. PMID- 1923546 TI - [Specific gene deletion in patients with cystic fibrosis: pilot study of a small patient cohort]. AB - Identification and molecular cloning of the cystic fibrosis (CF)-gene was a major progress in genetic counseling of families with one or more affected children. In caucasian families about 70% of the CF-patients show a homozygous or heterozygous deletion of one amino acid, that is phenylalanine at position 508 (delta F508). In a pilot study we examined the DNA of 14 CF-patients for F508 deletions. DNA was amplified by PCR and hybridized with a oligonucleotide-probe specific for the mutation containing CF-gene. Surprisingly all of the patients had a deletion of F508 of at least one allele (10 for both alleles, 4 for one allele). This method is of great importance for carrier-diagnosis. The finding of these or other deletions within the CF-gene may represent a prognostic marker for this disease. PMID- 1923547 TI - Serum prolactin concentration and hypothalamic-pituitary hormone release in CF children. AB - Some experimental data from animals suggest that prolactin (PROL) is involved in sweat production and modulates the chloride concentration of sweat. We determined the serum PROL level by RIA in 38 CF-patients (age: 3-24 years) and 48 patients with bronchial asthma (age: 2-18 years) and found no concentration differences between the two groups each taken as a whole; the TSH level was increased in CF (p less than 0.05). Separate analysis showed a significantly higher PROL level in CF-females and in CF-children (male and female) under 12 years old (p less than 0.05). To assess the hypothalamic-pituitary system we performed the metoclopramide test (by Cerucal) on 30 children suffering from CF (n = 10), bronchial asthma (n = 10) or pyelonephritis (n = 10) for PROL, LH, FSH, TSH and HGH. The hormone release was normal for all kinds checked in all groups of patients. Hence it follows that the neurohormonal system of prolactin is normal in CF-patients and the increased serum PROL and TSH concentrations in CF should be seen as a regulatory phenomenon but not as a mechanism associated with the basic defect of the CF-disease. PMID- 1923548 TI - [Diagnosis, therapy and prevention of necrotizing enterocolitis in newborn infants]. AB - The necrotizing enterocolitis is a severe and frequently fulminant disease with a considerable mortality. The main event is the enteral septicemia. Only prompt diagnostics and adequate therapy permit the survival of the newborns. The most important aspects of signs and symptoms, diagnostics and therapy as well as course of disease and prophylaxis are delineated, whereas the problems of pathogenesis are excluded. PMID- 1923549 TI - [Microbiological studies in children in nurseries (Study A)]. AB - From 1986 to 1988 76 children, aged from 13 to 36 months, being in 8 creches of a large town were tested microbiologically in the phases: healthy (0), initial phase of acute respiratory disease (A), 2nd and 4th week of convalescence (R2, R4). It was possible to proof bacteria 253 times. 17 various kinds of bacteria were found. Bacteria of catarrhal group (30.8%) and streptococcus pneumoniae (28.4%) dominated among other bacteria. In phase 0 they were isolated in 24% of the children, in phase A in nearly 50%, in phase R2 and R4 in 21 and 14%, respectively in 26 and 25%. Most kinds of bacteria followed this trend. This was not the case with the virological and mycological results. 14 isolations of viruses with 10 various kinds and 30 viro-serological proofs of 8 various kinds did not reflect the actual situation with only 2 quadruple increases of titre during the disease. The detection rate of Candida albicans (24% in healthy) is situated in value expected. Conclusions are drawn. PMID- 1923550 TI - [Microbiological studies on nursery children susceptible to infections]. AB - In a microbiological paper from 1986 to 1988 dealing with 76 children aged from 13 to 36 months in 8 creches of a large town, it could be found that 24 of these children were susceptible to infections and it is established that there were 3-9 bacteria per child. The most important bacteria were: Staphylococcus aureus, Streptococcus pneumoniae, haemolytic streptococci. But bacteria of the catarrhal group played a certain role, too. In 8 of these children dispositional factors and factors caused by exterior conditions of life (risk factors) could be shown, in 50% out of them a prolonged convalescence and in 50% after 4 weeks a reinfection after acute respiratory disease (ARD). The course of phases of ARD (initial phase, 2. and 4. week of convalescence) is introduced from microbiological view at all children. We point out the meaning of microbiological diagnostics with subsequent aiming sanitation by children susceptible to infections with risk factors. PMID- 1923551 TI - [Morbidity studies in children's nurseries]. AB - In 1986-1988 the indices of absence morbidity taken from monthly reports of creches were registered in 8 creches of Dresden and were compared with the real total morbidity, which had been registered with help of a symptom catalogue for one year. The total morbidity amounted to more than the double of absence morbidity, the total of the illness days per case amounted to 8.42 days and the days of absence morbidity amounted 7.3. The description of infection groups with help of quarters (according to Adam) on the basis of the registered total morbidity showed differences with regard to: average illness period per case (children susceptible to infections: 9.33 d; children robust to infections: 6.82 d) and average recurrence period (children susceptible to infections: 15.7 d; children robust to infections: 78.2 d). Probable causes of susceptibility to infections and conclusions hence to be drawn. PMID- 1923552 TI - [Methods in individualized pharmacotherapy of diseases of the digestive and the respiratory systems in children]. AB - The possibility to forecast pharmacotherapeutic effect in children with chronic diseases of breathing and digestion was studied. It was established that the use of pathogenic and associative markers, characteristic of the background state of a child as compared to individual peculiarities of pharmacokinetics and pharmacodynamics of a certain drug, will allow to forecast the efficiency of drug treatment of chronic diseases of breathing organs (bronchitis, pneumonia, asthmatic bronchitis) and digestion (gastritis, cholecystocholangitis). The use of aminophenazone marker in children with above mentioned pathology became the basis of research into efficiency of spasmolytics with similar type of metabolism (papaverini hydrochloridum, aminophyllinum, drotaverinum). Mathematic models of spasmolytics efficiency forecast was developed by many factor computer analysis. PMID- 1923553 TI - Prognostic determinants in the management of prostatic cancer in Ife. AB - Sixty-two patients diagnosed as early and advanced cancer of the prostate gland were studied under three categories. The survival rate of those diagnosed early was 80% in the first five years while the overall survival rate in the series was 19.23%. The prognostic determinants in all categories while under therapy was, however, similar. The study confirmed that poor prognostic features were body weight of about 40 kg, haematocrit below 20%, Urea level of 10 mmol/lit and above, raised white cell count, raised erythrocytes sedimentation rate and total confinement to bed. The paper concluded that these findings, in a local pilot study, are of significance and sufficient value to merit further study and clinical evaluation. PMID- 1923554 TI - Total parenteral nutrition (TPN) in the critically ill patient. AB - A study has been carried out on the effectiveness of a total parenteral nutrition (TPN) program on 12 patients in intensive care units (ICU). Conclusions have been drawn from biohumoral parameters during the first fornight's stay in the ICU. Results, relating to the re-equilibrium of the glycid and protydic sectors, varied in respect of their temporal distribution. There was in fact a stabilisation, if only temporary, in the glycemy, in the very first days, while the proteic metabolism figures showed a recovery leading to stabilisation only in the second week. PMID- 1923556 TI - The determination of prolamins in gluten-free food. Introductory remarks. AB - This paper gives the considerations on the Codex Alimentarius Standard on gluten free food and the levels that are proposed as a new standard. Background for the level of tolerance for gliadin in coeliac patients is given as well as the arguments for the choice of an enzyme immunochemical method for the determination of gliadin in gluten free food. PMID- 1923555 TI - Use of calcitonin in 20 patients suffering from postmenopausal osteoporosis. A proposal for a therapeutical scheme. AB - The treatment of postmenopausal osteoporosis has been thoroughly studied in recent years, because of the large diffusion of this condition. The therapeutic use of synthetic calcitonin from salmon, associated with oral calcium, has been successfully performed in 18 women out of 20, aged 55-65 years old, all suffering from postmenopausal osteoporosis without bone fractures. The dose used (100 MRC), the type of administration, and the duration of treatment (1 injection i.m. daily, for 30 days, and 1 every other day, for the next 60 days), can be taken as a useful therapeutical scheme, also by the general practitioner. PMID- 1923557 TI - Chemistry, coeliac-toxicity and detection of gluten and related prolamins in foods. AB - Some recent advances in the understanding of the chemistry of gluten proteins and its relationship to the toxicity of different fractions in coeliac disease (gluten intolerance) is reviewed. Most recent studies on gluten toxicity have used in vitro analyses of cellular immune activation by gluten fractions and peptides. Our work indicates that gliadin is the most active of the different protein families found within the wheat grain and that a specific peptide sequence located in the amino terminus domain of alpha-gliadin and containing the sequence proline-serine-glutamine-glutamine was most active. Improvement in the dietary management of coeliac disease is possible by use of test kits for the detection of gluten in foods. Both laboratory kits and home test kits (suitable for use by individual coeliacs) are available and reliably detect gluten from wheat, rye and barley even after cooking or baking. PMID- 1923558 TI - Effects of small amounts of gluten in the diet of coeliac patients. AB - A diet excluding wheat, oats, rye and barley is the cornerstone of the treatment of coeliac patients. Such a gluten-free diet (GFD) is recommended irrespective of the presence of symptoms. Maintenance of a strict GFD is not a simple matter, as small amounts of gluten capable of causing relapse have been identified in several previously unsuspected sources, thanks to the recent availability of sensitive detection assays. To date there is no definition as to what amount of gluten in the diet might be tolerable. Compliance to the GFD is a problem, particularly in certain groups of patients (e.g. adolescents). Small amounts of gluten in the diet often do not cause clinical symptoms, nor increased serum levels of antigliadin antibody, nor gross changes of the jejunal histology; nevertheless, they seem to be able to activate mucosal cell-mediated immunity. This finding represents a warning in view of the recently reported protective effect of GFD against malignancies. In conclusion, all present evidences give strong support for advising all patients to adhere to a strict GFD for life. PMID- 1923559 TI - Pulmonary function in patients with pleural effusion of varying magnitude and fibrothorax. AB - Pulmonary function was studied in sixty patients with pleural effusion and seventy patients with fibrothorax. The patients with pleural effusion were divided into three groups according to the extent of the effusion. The patients were submitted to spirometry and arterial blood gas analysis. The effects of pleural effusion on pulmonary function is evaluated with regards to the size of effusion. Small-size pleural effusion little affects arterial oxygen tension. Pleural effusion and fibrothorax have a similar pattern of pulmonary function. PMID- 1923560 TI - Classification and prognostic evaluation in multiple myeloma. A retrospective study of relationship of survivals and responses to chemotherapy to immunological types, 20 single prognostic factors, 15 clinical staging systems, and 6 morphological classifications. AB - In a group of 136 completely followed up patients with multiple myeloma, the prognostic significance of the immunological myeloma types, of 20 different single prognostic factors, of 15 clinical staging systems, and of 6 morphological classifications was retrospectively investigated by means of the calculation of mean survivals, survival curves, and responses to chemotherapy. A univariate analysis was employed in order to correlate each prognostic parameter at presentation with the survival in the whole group; a multivariate analysis according to the Cox's hazards regression model was used in order to select the most powerful prognostic variables. The patients were grouped according to the myeloma immunological types, to the mean value of each single prognostic factor, and to each stage of the clinical and morphological systems. Causes of death were also related to immunological multiple myeloma types. All single variables, except age and serum calcium, presented a significant relationship with the survival, even if at different significance levels. Cox's regression model selected among them, serum levels of beta 2-microglobulin, percentage of bone marrow plasma cells, hemoglobinemia, lytic bone lesions, and Bence-Jones proteinuria as the most significant factors related to survival. Each clinical and morphological staging system divided groups of patients with significant differences in mean survivals, or in survival curves, or in response to therapy. Multiple myeloma type IgA and micromolecular, with Bence-Jones proteinuria, and type lambda were associated with a poor prognosis, with low therapeutical response, and with the development of fatal renal failure. All these parameters, together with new prognostic factors, are useful in the prognostic evaluation, and, when applied in different steps of the diagnosis and the therapy, allow of studying the clinical course of multiple myeloma under different perspectives, in order to have a more complete picture of the disease and of the single patient. PMID- 1923561 TI - Testosterone and other gonadal factor(s) restrict the efficacy of genes controlling resistance to Plasmodium chabaudi malaria. AB - The effect of circulating concentrations of testosterone (Te) on resistance to Plasmodium chabaudi malaria was investigated in the H-2 congenic mouse strains C57BL/10, B10.A, B10.A(3R), B10.A(4R), and B10.D2. Te-levels were determined by radioimmunoassay and resistance was expressed in terms of percent self-healers after challenge with 10(6) P. chabaudi-infected erythrocytes. Our data indicate: (i) Females and castrated males reveal very similar interstrain variations of resistance. These do not correlate with the interstrain variations of the Te levels. This is consistent with the view that resistance to P. chaubaudi is controlled by genes of the H-2 complex and genes of the non-H-2 B10-background, (ii) The polygenic control of resistance is inefficacious at high Te-levels. This is evident as high susceptibilities of males, Te-treated females and Te-treated castrated males. Moreover, high Te-levels correlate with susceptibilities to P. chabaudi within mice of the same sex of a given strain, (iii) B10-males chemically castrated using buserelin display the same low Te-level as those surgically castrated. The latter become resistant, while the former remain as highly susceptible to P. chabaudi as untreated B10-males. Obviously, other gonadal factor(s), besides Te, impose restrictions on genes controlling resistance to P. chabaudi malaria. PMID- 1923562 TI - Genetic studies on a major merozoite surface antigen of the malaria parasite of rodents, Plasmodium chabaudi. AB - Diversity in a major merozoite surface antigen (MSA-1) of Plasmodium chabaudi has been examined using a panel of monoclonal antibodies (MoAbs). The antigen was found to be different in each of twelve cloned isolates, as shown by its reactivity with the MoAbs in immunofluorescence tests. In genetic crossing experiments, the diverse forms of this antigen were shown to be determined by allelic variation of a single gene. Recombination occurred between the MSA-1 gene, a second blood stage antigen and enzyme markers. PMID- 1923563 TI - Detection of antibodies against glycolipids of Echinococcus multilocularis metacestodes in sera of patients with alveolar hydatid disease. AB - Glycosphingolipids extracted from Echinococcus multilocularis metacestodes were tested against sera from patients with alveolar hydatid disease (AHD). The tests were performed first by ELISA then by immunostaining on thin layer chromatography. A binding between the parasite glycolipids and antibodies of AHD human sera was observed by ELISA. The glycolipids related to this binding were specifically parasite neutral glycosphingolipids. No reaction was observed with parasite acid glycolipids nor with neutral glycolipid extracts from human or mongolian gerbil erythrocytes. Comparison between absorbance values of 25 AHD sera and 20 control sera showed significant differences. Similar results were obtained with sera from hydatid cyst patients. Sera from patients with other parasitoses (schistosomiasis, strongyloidosis or paludism) were also tested. The reactive fractions were identified by immunostaining on thin layer chromatography with AHD sera, they were neutral glycosphingolipids containing at least two carbohydrate residues. These results were compared with chromatograms obtained with hydatid cyst human sera and discussed. PMID- 1923564 TI - Genetic control of the immune response to Trichinella spiralis: recognition of muscle larval antigens. AB - Host antibody recognition of muscle larval (ML) antigens of Trichinella spiralis was examined. Monoclonal antibodies (MoAbs) to known host protective ML antigens have been produced in order to aid this examination. Eleven strains of mice with independent MHC haplotypes and seventeen T. spiralis infected human patients were all found to recognize the same three major antigens as the monoclonal antibodies; i.e., of mw 41, 46 and 55 kD. However all serum samples tested also recognized further ML antigens and this recognition varied with the individual or strain. This variation in antigen recognition also applied to the MoAb. Mutual inhibition studies demonstrated that even where the MoAb apparently recognized the same antigens, specific epitope recognition was disparate. Hence some of the major antigens recognized by hosts of T. spiralis, regardless of whether vaccinated or infected, correspond with antigens which have considerable host protective properties. There also appear to be a number of epitopes upon these antigens and the biological implications of this are discussed. PMID- 1923565 TI - Circulating filarial antigen in cats infected with Brugia pahangi is indicative of the presence of adult worms. AB - Using counterimmunoelectrophoresis with rabbit antisera raised against soluble extracts of adult females of Brugia pahangi parasite antigen was detected in the serum of all cats repeatedly infected with B. pahangi. Antigen was never detected in uninfected cats. The antigen was associated with the presence of adult worms. Antigen was detected consistently in a cat that was amicrofilaraemic but at autopsy harboured only two or three adult worms. Conversely, some cats showed slowly declining numbers of microfilariae and, in these, circulating antigen declined before the number of microfilariae. Eventually no antigen was detectable in circulation whereas microfilariae, although in diminishing numbers, were still present. At autopsy no adult worms were found in these cats. Antigen also appeared in several cats before they became microfilaraemic. PMID- 1923566 TI - Susceptibility of N'Dama and Boran cattle to tsetse-transmitted primary and rechallenge infections with a homologous serodeme of Trypanosoma congolense. AB - Eight trypanotolerant N'Dama cattle controlled an infection of Trypanosoma congolense ILNat 3.1 transmitted by Glossina morsitans centralis, more efficiently than a group of similarly infected trypanosusceptible Boran cattle. All eight N'Damas maintained their PCV above 15% throughout the primary infection whereas the PCV of six of the eight Borans dropped below 15%; these latter animals were treated with diminazene aceturate to prevent possible death. Lymphocyte, neutrophil and platelet counts also decreased in the Boran during the primary infection. In contrast, a lymphocytosis was observed in the N'Dama; and although the neutrophil and platelet counts decreased, the drop was less severe than in the Boran. Two years after the primary infection and immediately prior to a homologous rechallenge infection, all eight N'Damas had neutralizing anti metacyclic trypanosome variant-specific antibodies present in their sera compared to five of the eight Borans. Following the homologous rechallenge infection the eight N'Damas became parasitaemic but there were no alterations in their erythrocyte or leukocyte counts. The Borans became highly parasitaemic and developed severe, chronic anaemia and leukopaenia. Thus, the trypanotolerant N'Damas controlled a primary infection of T. congolense more efficiently than trypanosusceptible Boran cattle and eliminated a homologous rechallenge infection without the pathology associated with the disease. PMID- 1923567 TI - Susceptibility of N'Dama and Boran cattle to sequential challenges with tsetse transmitted clones of Trypanosoma congolense. AB - The susceptibility of N'Dama cattle (Bos taurus) to four consecutive infections with different tsetse-transmitted clones of Trypanosoma congolense was compared with that of Borans (Bos indicus). All animals were aged 13 months at the start of the study and had been born and raised free from trypanosomiasis under the same management and nutritional conditions, thereby limiting environmental factors that could have influenced susceptibility. While cattle of both breeds were equally susceptible to the establishment of trypanosome infections, the N'Damas exhibited superior resistance. Despite infection with virulent parasites, the N'Damas gained weight at the same rate as uninfected control animals, they did not develop anaemia to the extent that trypanocidal drug treatment was required, and all made a spontaneous recovery to normal haematological values within two to four months. In contrast, all the Borans needed treatment during the course of the four infections because of severe anaemia and showed markedly reduced liveweight gains. These clinical differences in the N'Damas were associated with two repeatable characteristics, namely, the ability to control parasitaemia and to 'resist' anaemia, processes that did not appear to be linked. Also in contrast to the Borans, the N'Damas were able to mount accelerated haemopoietic responses, resulting in the reduced severity of anaemia following a primary infection. These findings pose the question as to whether the ability to control parasitaemia and to 'resist' anaemia could be used as criteria for identifying resistant or trypanotolerant cattle. PMID- 1923568 TI - [An experimental study of the interrelations of Leishmania (Sauroleishmania) gymnodactyli and the sandfly Sergentomyia arpaklensis (Diptera: Phlebotominae)]. AB - Morphology, development and behaviour of Leishmania gymnodactyli in the sand fly Sergentomyia arpaklensis at different stages of blood digestion have been studied. It has been shown that leishmaniae reproduce readily and develop normally inside the food ball of sandflies. The dense peritrophic membrane is not destroyed at the end of digestion and is an insuperable obstacle for leishmaniae. Promastigotes of leishmaniae, being involved in the peritrophic membrane, are excreted together with undigested food that excludes their transmission through the bite of S. arpaklensis. PMID- 1923569 TI - [A new type of pleurocercoids in the genus Diphyllobothrium from smelts in the Far East of the USSR]. AB - The research has demonstrated that 35.8% of Hypomesus pretiosus Girard and 55.9% of Osmerus eperlanus dentex Steindachner in various regions of the Far East of the USSR (Khabarovsk and Primorye territories and Sakhalin) are affected by diphyllobothriid larvae of a hitherto unknown type, indicated as the G type. Parasites are localized on the internal organs of a intermediate host such as esophagus, stomach, liver and genital organs. Diphyllobothriid larvae of the G type do not invade man, thus the indicated fishes are not epidemiologically significant in spreading diphyllobathriasis among the population in the Far East of the USSR. PMID- 1923570 TI - [The effect of the physiological age of Dermacentor marginatus (Ixodidae) ticks on their infection with and the infiltration of the tick-borne encephalitis virus into the saliva]. AB - The decisive effect of physiological age of ticks on the infection of their saliva was revealed by means of parenteral infection of D. marginatus females with tick-borne encephalitis virus. The virus was not found in the saliva of young individuals of instar II. Maximum number of cases of saliva infection was recorded in mature ticks of instar III (50%). It was established that the infection of saliva did not depend on the amount of virus in the tick's body. Less susceptibility to the virus of young individuals, associated probably with the way of infection, was noted. Under light microscopy there were observed no significant age differences in salivary glands of ticks of instars II and III. The infection of saliva of young individuals is, apparently, opposed by the barrier of fat body on the way of virus to salivary glands, depending on the age of ticks. The barrier is supposed to have an influence under natural transphase infection of ticks. PMID- 1923572 TI - Avianca flight 052: a nurse's perspective. PMID- 1923571 TI - [The characteristics of the relationships of arthropods of the refuge complex with the causative agents of transmissible viral infections in bird rookeries]. AB - The isolation of viruses of tick-borne encephalitis, West Nile fever, and Omsk hemorrhagic fever from arthropods of nests of colonial birds (rook, sand martin, tree sparrow, Laridae) in different zones of West Siberia (from tundra to steppe) has been analyzed. The role of gamasid mites, hematophages and saprophages, characteristic inhabitants of nests of colonial birds, and of the tick Ixodes lividus in connection with their biology, coadaptation with hosts, microclimatic nest conditions, etc. has been evaluated. It has been concluded that the whole nest community of arthropods in a nest rather than one infected individual has to be regarded as an infective unit in colonies. PMID- 1923573 TI - Unit rod segmental spinal instrumentation for the treatment of neuromuscular scoliosis. AB - The Unit Rod was developed at the Hospital for Sick Children in Toronto for the surgical correction of scoliosis and pelvic obliquity associated with neuromuscular disease. Its unique contour and design allows fixation into the pelvis and decreases complications encountered with other segmental systems. Perioperative nursing care and the psychosocial impact of surgery on the family are addressed in this article. A case study is included. PMID- 1923574 TI - Handling and disposal of infectious waste in the office setting. AB - Anyone who generates infectious waste must now comply with infectious waste regulations, which vary throughout the nation and are changing rapidly. The orthopaedic nurse in the office setting must keep informed of these changes, and may also be the key to complete and correct compliance with the rules and regulations. Following a proper infectious waste protocol in the office requires an understanding of the infectious waste rules and guidelines as they apply in your state. Before choices can be made on how to comply with the guidelines, you need to assess your practice and the kinds of waste it generates. PMID- 1923575 TI - The impact of Duchenne muscular dystrophy on families. AB - To understand the experiences of families having a child with Duchenne muscular dystrophy, the investigator studied three families for 10 weeks with a follow-up at 1 year. Six themes recurred in the common experiences in the families: the erosion of hope for normalcy; society's confirmation of the impossibility of normalcy; the dynamics of the family; a smaller world; letting go or hanging on; and things must change. This article illustrates these six themes, compares them to Roy's Adaptation Model, and discusses nursing interventions. PMID- 1923576 TI - Increase your communication confidence through media exposure. PMID- 1923578 TI - Antibiotics: cephalosporins. Drawing room comedy to Sardinian sludge. PMID- 1923577 TI - Collaborative practice: a coordinated approach to patient care. AB - Mr. Michael is a patient who was cared for at our institution when surgery for a severe rheumatoid neck deformity was planned for him. This article demonstrates how preplanning, collaborative practice, and communication among the health care team members successfully facilitated a positive outcome for this patient. PMID- 1923579 TI - Celebrating the orthopaedic nurse. PMID- 1923580 TI - Healthy People 2000: a framework for nursing action. PMID- 1923581 TI - Acquired torticollis in children. AB - Acquired torticollis in children is a symptom that may be due to a number of underlying causes, some of which are severe and life threatening. Musculoskeletal, ophthalmologic, infectious, neurologic, and neoplastic conditions may present early with only torticollis. Because torticollis is a symptom, the broad spectrum of possible diagnoses requires a thorough and methodical workup. A wide variety of tests may be necessary, as well as specialty consultation. No matter how common or rare the disorder, it must be considered when evaluating a child with acquired torticollis. The first step in evaluation is always a careful and complete physical examination. An outline of the disorders associated with torticollis is presented, as are illustrative case histories. PMID- 1923582 TI - Fluid contamination during orthopaedic procedures. A study of incidence, location, and prevention. AB - Certain orthopaedic procedures may expose health care providers to contamination of scrub clothing, personal undergarments, and/or skin by patients' body fluids. The incidence and site of fluid contamination were studied for an orthopaedic surgeon and his assistant during 54 orthopaedic operations from March through May 1989. Contamination was recorded in 35 of the cases (65%) for the surgeon, and in 37 (69%) for the assistant. The sites of contamination spanned the length of the lower extremities, with an overall 34% incidence above the knee. The surgeon and assistant then monitored fluid contamination during 43 cases from March through May 1990 while wearing water-impervious surgical pants. An additional 16 clinicians also tested these pants and answered questions regarding their comfort and utility. No cases of fluid contamination were recorded during the second phase of the study. The garment was reported to be comfortable and did not appear to add a heat factor, even with the use of lead aprons during fluoroscopic procedures. PMID- 1923583 TI - Reduced bone-mineral content is a risk factor for hip fractures. AB - To evaluate skeletal osteopenia as a risk factor for hip fractures, we measured bone-mineral content in 18 postmenopausal women (aged 50 to 85 years) within 5 days of sustaining a nontraumatic hip fracture. We compared these findings to those in 50 women without a hip fracture who were matched for age, postmenopausal years, height, and weight to the study participants. With the use of dual-photon absorptiometry, the hip fracture patients were found to have a significantly reduced mean bone-mineral content (P less than .005) at three sites in the unaffected hip and a marginally lower mean value (P less than .057) in the lumbar spine as compared to the controls. Other findings in the fracture group included a history of little physical activity, diminished visual acuity, and a somewhat high prevalence of psychiatric/organic brain disorders. Reduced bone mass is an important risk factor for hip fractures. However, other conditions such as physical inactivity, reduced visual acuity, and cognitive impairment may also affect the tendency to fall and/or the ability to cushion the impact of a fall and thus further increase the risk of fracture occurrence. PMID- 1923584 TI - Patient guide. Pain. AB - During the past 20 years, the protective mechanism of pain has received a great deal of attention from the scientific community, with promising results for the millions of people whose lives are dominated by chronic discomfort. Many pain causing problems are now better understood and, as a result, are more effectively treated. Progress in understanding the chemistry of the brain's own painkillers- the endorphins--has spurred research and production of new categories of medication, and various forms of self-help have become an important part of effective pain control. PMID- 1923585 TI - Tips of the trade #38. The Herbert screw in closed reduction and internal fixation of the Jones fracture. AB - A technique of using a cannulated Herbert screw is presented for addressing the troublesome Jones fracture. This closed intramedullary fixation technique allows early healing without many of the screw head problems encountered in the more traditional AO screw techniques. PMID- 1923586 TI - [Gene mutations of cystic fibrosis in Brittany population]. AB - Eighty percent of chromosomes from cystic fibrosis children in Brittany exhibit the major gene mutation (delta F 508) consisting in deletion of three nucleotide pairs. Eighty-seven chromosomes without the delta F 508 mutation were studied for as yet undescribed gene mutations. A large number of mutations were located in exons 10 and 11. Consequently, a global strategy for identifying mutations in these exons was developed. Analysis of pedigrees of cystic fibrosis patients in Brittany evidenced a clear founder effect. Appropriate prevention strategies will therefore be developed. PMID- 1923587 TI - Cystic fibrosis gene mutations, and correlation with clinical manifestations. PMID- 1923588 TI - CF DNA-diagnosis and gene mutation analysis: data from East Germany. PMID- 1923589 TI - Microbial lung infections: new therapeutic strategies. PMID- 1923590 TI - [Bronchial mucins and infection in cystic fibrosis]. PMID- 1923591 TI - [Neutrophils: mediators of bronchial destruction in patients with cystic fibrosis]. PMID- 1923592 TI - [Iron transport and role of pyoverdines in infectivity of Pseudomonas aeruginosa. Therapeutic incidences]. PMID- 1923594 TI - [Bronchial hyperreactivity and cystic fibrosis]. PMID- 1923593 TI - [Inhibition of alignate biosynthesis in mucoid strains of Pseudomonas aeruginosa]. PMID- 1923595 TI - [Cystic fibrosis and allergic bronchopulmonary aspergillosis]. PMID- 1923596 TI - [Ursodeoxycholic acid. Physical properties and hepatoprotective activity]. AB - In patients with cystic fibrosis, obstruction of bile ductules by mucus plugs and hepatocellular retention of hydrophobic bile acids including chenodeoxycholic acid may induce cholestasis and biliary cirrhosis. Ursodeoxycholic acid is a hydrophilic bile acid whose physicochemical characteristics differ markedly from those of chenodeoxycholic acid. Critical micellar concentration is higher and surface activity lower with ursodeoxycholate, whose micelles induce less solubilization of lecithin and cholesterol. In animal models, ursodeoxycholate increases bile excretion and prevents cholestasis and cytolysis induced by hydrophobic bile salts. Taken together, these data suggest that ursodeoxycholate therapy may have a beneficial effect on cystic fibrosis-related hepatobiliary disorders. PMID- 1923597 TI - [Use of ursodeoxycholic acid in the treatment of hepato-biliary complications in cystic fibrosis]. PMID- 1923598 TI - [Portal hypertension in cystic fibrosis. Value of partial splenectomy]. PMID- 1923599 TI - [Physiopathology of pancreatic involvement in cystic fibrosis]. PMID- 1923600 TI - [Trypsin in the meconium in healthy subjects and subjects with cystic fibrosis]. PMID- 1923601 TI - [Energy expenditure: contribution of doubly labelled water]. PMID- 1923602 TI - [The role of glycosaminoglycans in the local regulation of hemopoiesis in exposure of the body to extreme factors]. AB - The authors studied the role of glycosaminoglycans as component of hematopoiesis inducing microenvironment in the regulation of hematopoiesis. Following injection of preparations of these compounds to experimental animals (male CBA mice), their concentration changed most markedly in the bone marrow and spleen. The effect of acid glycosaminoglycans on the hematopoietic cells is realized through an increase of the concentration of calcium, cAMP, and leads to activation of granulocytopoiesis. It was shown in experiments with heparin that desulfation has no effect on their hematopoietic activity. PMID- 1923603 TI - [The mechanisms of the disordered regulation of hematopoiesis in the late periods after the administration of cytostatic preparations]. AB - It was demonstrated on an experimental model of cytostatic disease induced by a course of injections (1/10 LD50 for 10 days) of antineoplastic agents with various mechanism of action (doxorubicin, vinblastine, cyclophosphamide) that persistent (for 6 months) disorganization of the morphological composition of the thymus and other lymphoid organs is attended by inhibition of the functional activity of the T-cells of the immunity system. It is suggested that the weakened control (on the part of the thymus) due to the effect of the cytostatics may lead to disorders of the processes of proliferation and differentiation of the hematopoietic cells and impairment of the bone marrow morphological composition in late-term periods after cytostatic treatment. PMID- 1923604 TI - [The role of the autonomic nervous system in the mechanisms regulating hemopoiesis in stress]. AB - It was demonstrated in experiments on rats that a neuroleptic and alpha adrenergic blocking agent inhibited whereas a ganglion blocking agent and beta adrenergic blocking agent delayed activation of granulocytopoiesis in immobilization stress, while M-cholinergic blocking agent had practically no effect on this process. Blockade of alpha- or beta-adrenergic receptors causes an essential reduction in the number of hematopoietic islets, precursor cells of granulocytopoiesis in the bone marrow, and level of colony stimulating activity in blood serum and supernatants of lipopolysaccharides and concanavalin-A stimulated myelokaryocytes. However, in immobilization stress the initiator and potentiator effect of stimulation of beta-adrenergic blocking agents on processes of granulocytopoiesis was much less marked than that of alpha-adrenergic blocking agents stimulation. PMID- 1923605 TI - [The role of the autonomic nervous system in regulating bone marrow erythropoiesis in stress]. AB - Injection of one of the pharmacological neurotropic antagonists (neuroleptic, ganglionic blocking, alpha- or beta-adrenergic blocking agents) abolished the phenomenon of erythropoiesis activation in immobilization stress in mice. Blockade of alpha- and beta-adrenergic receptors significantly reduced the number of erythroid colonies forming from cells of bone marrow culture in vitro and the erythropoietin level in blood serum and supernatants of bone marrow cells. The M cholinergic blocking agent had no effect on the bone marrow erythrokaryocyte content in immobilized animals. At the same time, stimulation of alpha- and beta adrenergic receptors led to a dose-dependent increase of the number of erythroid cells in the bone marrow of mice exposed to the effect of immobilization. PMID- 1923606 TI - [Patterns in the compensatory reaction of the precursor cell system of the bone marrow fibroblasts to ionizing radiation]. AB - Compensatory unspecific processes taking place in irradiated bone marrow stroma are caused by qualitative and quantitative reactions of the stromal cell populations to the damaging effect. The authors studied the regularities of the compensatory quantitative reaction of the stroma--the system of fibroblast colony forming units (CFUf) of guinea-pig bone marrow--to exposure to ionizing radiation. They confirmed the existence of a "reserve" of the bone marrow CFUf system whose cell elements acquire adhesive and mitotic activity in the immediate periods (60-90 minutes) after irradiation. It is shown that the character of the dose-effect curves according to the criterion of the absolute CFUf number 60-90 minutes after irradiation is determined by two processes: the death of stromal precursor cells in proportion to the irradiation dose, and activation of the "reserve" population of the CFUf system proportionally to the level of the action of the ionizing radiation. The quantitative degree of activation of the CFUf "reserve" is characterized. Radiosensitivity was appraised in vivo of two guinea pig bone marrow CFUf populations forming dense and loose fibroblast colonies in a monolayer culture. PMID- 1923608 TI - [Bone marrow erythroblast islets in burns]. AB - The character of changes of rat bone marrow (BM) erythroblastic islets (EI) was studied in different periods after III degree burn of 15% body surface. Marked differences in the qualitative EI composition were revealed in the cortical generative zone and the central maturation zone of control animals. Proliferative EI forms predominated in the generative zone and involute EI in the maturation zone. The absolute number of EI in BM reduced in the early period of burn anaemia, probably due to proteolysis mainly through a decrease of involute EI in the maturation zone. The number of EI in BM reached minimal level in the late period of burn anaemia. Inhibition of erythropoiesis in the EI was manifested by a decrease in the content of proliferating forms of EI predominantly in the BM generative zone, probably due to slower involvement of erythroid CFU cells in erythropoiesis and inhibition of specific functions of EI macrophages. PMID- 1923607 TI - [The quantitative and qualitative characteristics of the reaction of committed bone marrow cell precursors in rats to burn trauma]. AB - The article describes the dynamics of colony-forming units in diffusion chamber of tubular bone marrow compartments 1 and 7 days after a burn. It was found that under normal conditions the activity of the axial part of the bone marrow is twice that of the cortical part. After a burn the inductive capacity of the cortical part becomes equal to that of the axial part. A wider qualitative spectrum of colonies occurs due to the effect of short-distance humoral factors (eosinophils, mast cells). PMID- 1923609 TI - [The kidney-dependent mechanism of posthemorrhagic erythrodieresis]. AB - Kidney-dependent erythrodieresis (hemolysis) is intensified 15, 30, 60, and 180 minutes after acute uncompensated blood loss in animals (rats, mice). The intensification occurs through increase of blood serum hemolytic activity, increase of the number of autoplatelet-forming cells in the blood of the spleen and kidneys, activation of the mononuclear phagocyte system, and destruction of erythrocytes during perfusion through the renal vessels. PMID- 1923610 TI - [The effect of massive blood loss on the adrenaline-sensitive pool of the blood neutrophils]. AB - Experiments were conducted on models of immobilization stress and hemorrhagic shock in rabbits to study the changes in the ability of intravenously injected adrenaline (A) to induce blood neutrophilia due to the escape of parietal neutrophils into circulation. It is shown that immobilization stress, just like A infusion, leads to neutrophilia. In contrast, in hemorrhagic shock neutropenia develops and the response to A disappears. Such changes in massive blood loss are interpreted by the authors as transition of the marginal (physiological) adhesion of neutrophils in the vascular system to pathological adhesion characteristic of inflammatory reactions. PMID- 1923611 TI - [Pulling back slightly the covers of the unknown in the physiology and pathology of the blood microcirculation]. PMID- 1923612 TI - [Disordered lymphoid regulation of hematopoiesis in iron-deficiency anemia]. AB - Iron-deficiency anemia (IDA) in rats is attended by secondary cellular immunodeficiency. The authors studied the importance of lymphocyte dysfunction in the pathogenesis of hematological disorders in rats with IDA. Transplantation of lymphocytes from intact donors subjected to hypoxia to syngeneic recipients led to stimulation of erythropoiesis in them. The effect of "iron deficiency' cells was less manifest. It was established that the hematological disorders in IDA are lymphocyte-determined. This was also demonstrated in experiments on rats with IDA and changed functional condition of the lymphoid tissue. PMID- 1923613 TI - [The role of bone marrow macrophages in regulating erythropoiesis in different states of the erythron]. AB - Stimulation and inhibition of erythropoiesis were modelled in rats to study the functional condition of central macrophages of the erythroblastic islets (EI) in the bone marrow by determining the total content of lysosomes, pH of lysosomes, activity of acid phosphatase, and 3H-thymidine inclusion in DNA. The properties of the surface charges of the EI cells were judged according to the electrophoretic mobility, the number of acid glycoproteins--according to the staining of the preparations with alcian blue. It is shown that the intensity of erythropoiesis in the EI determines the studied values. Sensitivity of EI macrophages to erythropoietin was demonstrated in EI cultivation. PMID- 1923614 TI - [The effect of the humoral action of the cells from chick embryo hematopoietic organs on the colony-forming capacity of normal mouse bone-marrow cells and in activated erythropoiesis]. AB - The cells of chick embryo hematopoietic organs were cultivated together with mouse bone marrow cells in bicameral diffusion chambers under normal conditions and in activated erythropoiesis. The yolk sac cells inhibited colony formation on the 2nd, 4th days of development, the hepatic cells--on the 8th, 12th days, the splenic cells--on the 13th, 17th days, and the bone marrow cells--on the 15th day. The cells of the yolk sac sharply intensify the formation of colonies by the marrow mononuclears, in particular, on the 6th developmental day in activated erythropoiesis. The yolk sac (on the 4th, 6th days of development), the liver, and the spleen produce humoral factors which facilitate the formation of erythroid colonies by the marrow cells of mice. The cells of a 4-day-old yolk sac inhibit the formation of granulocytic colonies, and the synthesis of inhibitors ceases in a 6-day-old yolk sac. It is suggested that the synthesis of local humoral inhibitors of the proliferation of colony-forming units controls the intensity of hematopoiesis in the organ and, by reducing proliferation, facilitates the emergency of cells into differentiation independently, according to the law or under the effect of local humoral poetins. PMID- 1923615 TI - [The spatial-temporal organization of erythropoiesis in exposure of the body to hyperbaric oxygenation]. AB - A systemic approach to appraisal of the mechanisms of changes of erythropoiesis biorhythms in stress is suggested. The authors studied the daily and seasonal rhythms of serum erythropoietin (EP) level, the production of erythrocytes (PE), the kinetics of bone marrow erythroid cells, and the activity of lipid peroxidation (LPO) and G-6-PDG in peripheral blood erythrocytes in albino rats. As a stress factor hyperbaric oxygenation initiated LPO acceleration and change of PE circadian rhythm with mesor decrease. Increased production of erythrocytes with reduction of their life span was simultaneously revealed. The differences in acrophases and amplitudes of erythropoiesis values in different seasons are caused by changes of erythroid cell kinetics due to mobilization of terminal erythropoiesis. PMID- 1923616 TI - [The effect of exogenous heparin on the processes of colony formation from myeloid precursors and the formation of erythroblastic islets]. AB - Experiments were conducted on Wistar rats to study the comparative effect of exogenous administration of heparin (250 U) on the colony forming ability of committed myeloid precursors and the formation of erythroblast islets (EI). The results were recorded for 5 days. On the basis of the obtained data a primary selective effect of heparin on the granulocytic-macrophagal colony forming units in the diffusion chamber was revealed. The process of EI formation is affected only in the late periods (3rd-5th day) against the background of sharply stimulated myelopoiesis. A significant reduction of the number of EI is noted in this period. PMID- 1923617 TI - [The analgesic and anti-stress effects of middle-molecule peptides in a normal state and in thermal burns]. AB - Fractions of medium-weight molecular peptides (MWP) were isolated from blood of intact dogs and those with burns, which possessed the property of increasing the latency of the pain reaction in mice by 23-28% after intravenous infusion. The analgesic properties of MWP change essentially in the first 24 hours after the burn. The dose dependences of the antinociceptive effect of MWP have a marked non linear character. The studied MWP fractions also prevent involution of the thymus induced by 9-hour immobilization stress. An MWP fraction was isolated from the blood of dogs 12 hours after a burn; its intravenous infusion led to reduction of the thymus equal to that caused by 9-hour immobilization. The relationship of adaptational and damaging effects of MWP in thermal burns in discussed. PMID- 1923618 TI - [The adrenergic mechanisms of the inhibition of the gastric acid-forming function in acute stress]. AB - It was demonstrated in experiments on Wistar rats that blockade of central adrenergic structures by thymopentin and beta-adrenergic receptors by inderal prevents stress inhibition of hydrochloric acid secretion. Normalization of the antioxidative protection of the stomach which prevents activation of the processes of free-radical oxidation in it plays an essential role in the mechanism of the stress-protective effect of adrenergic influences blockade on the gastric acid-producing function. PMID- 1923619 TI - [A device for the mechanical division of the bone marrow in the tubular bones into axial and cortical zones]. PMID- 1923620 TI - [A method of screening evaluation for the presence of myocardial infarct in an experiment on rats]. PMID- 1923621 TI - [The general pathophysiology of the nervous system]. PMID- 1923622 TI - [The determination of cerebral hemodynamics in rats by means of tetrapolar impedance rheoencephalography]. PMID- 1923623 TI - [Can one study pathological physiology independently according to an individual plan?]. PMID- 1923624 TI - [The specificity of the mechanisms regulating hematopoiesis under different extreme exposures]. AB - The reactions of the hematopoietic tissue and the mechanisms of their development were studied in rats during blood loss and when they were suspended on the neck fold. The mechanisms of hematopoiesis regulation were found to be similar in principle in exposure to different stresses: activation of the erythropoietin system and increase of blood serum colony-stimulating activity occurred in both cases. PMID- 1923625 TI - [Coagulative myocytolysis and its outcome in homicide victims. Reflexions on its relative psychologic meaning]. AB - This research has been justified by the recent acquisitions about the pathogenic role that stress may play on myocardium, not only through the involvement of coronary vessels, but even through an action directed on the muscle fibres, which results in a coagulative myocytolysis with consequent fibrosis. The Author intended to verify the incidence of the above said cardiopathy, evaluating it with respect to the suprarenal glands changes, in the victims for homicide, mostly belonging to the criminal subculture of the province of Reggio Calabria. The choice of such a casuitic is based on the fact that the suprarenal glands study, carried out by the same Author on the above said victims since 1958 till today, has allowed to point out, excluding the cases of people accidentally involved in the crime (the so-called "innocent victims", typical morphological changes including all degrees of stress (acute, subacute or chronic), with the prevalence of those typical changes occurring in subacute or chronic forms, chiefly in the medullar gland. The research was carried out on the casuistic from two periods: 1st group: 1958-1975 (61 cases, 53 males, aged 10 to 73, mostly killed with fire-arms); 2nd group: November 1989-October 1990 (52 cases, almost exclusively males, aged 17 to 66, 51 of which killed with fire-arms, and one with a knife). The results are the following: 1) In the first group: a) 32 cases showed the presence of myocardial fibrosis striae, for the most part very thin, wavy and parallel to the myocytes; b) all the cases showed a hypercontracted aspect of the myocytes; c) 10 cases, belonging to the 32 cases with fibrosis, showed signs of acute myocytolysis; d) 13 cases showed mild signs of intimal fibrosis in the coronary arteries; e) 48 cases showed signs of subacute or chronic functional hyperactivity of the suprarenal glands, either in the medullar or in the cortical gland, often with signs of acute superstimulation; f) 12 cases showed exclusively signs of acute stimulation of the same glands; g) one case (innocent victim), showed suprarenal glands of normal aspect.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1923626 TI - Nucleolar organizer regions (NORs) in dysplastic and neoplastic epithelial lesions of the conjunctiva. AB - Using a silver staining technique (AgNOR technique), we have investigated the nucleolar organizer-associated proteins (NORs) in formalin-fixed paraffin embedded conjunctival specimens of 15 intraepithelial squamous carcinomas, 10 hyperplastic-dysplastic samples and 10 control epithelial fragments; the mean number of intranuclear black dots was determined for each case. A significant difference in the mean number of NORs was found when intraepithelial squamous carcinomas were compared with hyperplastic-dysplastic lesions (P less than 0.001); in addition, normal control conjunctiva and hyperplastic-dysplastic lesions were also discernible (P less than 0.05). PMID- 1923627 TI - [Does the analysis of DNA in myocytes have meaning?]. AB - It seems that polyploidisation of the heart muscle nuclei is a physiological phenomenon that increases in pathological conditions such as muscolar dystrophy, myocardial hypertrophy. We studied the nuclear DNA content of myocites, by means of cytofluorimetric determinations in different sites of the left free ventricular wall in five hearts affected by dilatative myocardiopathy. In all the different sites examined we revealed diploid and tetraploid nuclear content. Variable was the presence of 8N poliploid peaks: specifically 40% in the external third, 47% in the medium third and 73% in the inner third. 16N polyploid peaks were revealed only twice, and exactly in one medium third and in one inner third. These data, even if quite preliminary, suggest the presence of an increasing gradient of ploydisation from the external toward the inner part of the left ventricular wall. PMID- 1923628 TI - [Quantitative analysis of DNA using flow cytometry and immunocytochemical findings in 16 cases of cardiac myxomas]. AB - Recently some Authors focused nosological and biological aspects of the cardiac mixomas. Their neoplastic nature and origin from undifferentiated mesencymal cell with multipotential capability have been confirmed. Morphological and immunocytochemical aspects alone are not able to screen "sporadic" from "non sporadic" mixomas. The last are associated with local recurrence and distant embolization. "Non-sporadic" mixomas are also part of a heritable syndrome involving skin, endocrine tumors and lentiginosis. It seems that this kind of mixomas display a DNA tetrapoid pattern at DNA flow cytometry. In the series of the Authors, consisting of 16 operative mixomas, all but one showed a DNA diploid pattern. Only in one case the pattern was tetraploid. PMID- 1923629 TI - Microwave oven for improved tissue fixation and decalcification. AB - The present study reports on our experience on microwave (MW) fixation and decalcification. A common kitchen microwave oven was used. Autoptical material and biopsies from different organs were immersed in 10% formalin and MW irradiated varying time and power. Bone biopsies were immersed in 5% formic acid and MW irradiated. The tissues were then routinely embedded in paraffin. The results, checked on routinely stained sections, indicate that MW irradiation speeds up both fixation and decalcification. Optimal treatment conditions are indicated. PMID- 1923630 TI - Fine needle aspiration cytology in the diagnosis of non-neoplastic diseases of head and neck masses. AB - In this study, 3 patients with head and neck masses, which were suspicious of neoplastic compromise, were submitted to FNAC investigation. Two cases showed specific infection by Paracoccidioidomycosis and one by Actinomycosis. The cytologic findings were in agreement with histopathologic diagnosis and clinical follow-up; that results showes that FNAC importance in the diagnosis of non neoplastic masses could be explored in ambulatorial routine. PMID- 1923631 TI - Cytology of pulmonary samples after cancer radiation therapy. AB - Radiation-induced cytomorphologic atypia is presented. The cellular changes produced by radiation therapy were studied in cytologic samples from eight patients with bronchogenic carcinoma. Pulmonary specimens were obtained from sputum, and washing and brushing examination in patients before and after radiation. In all 48 samples with 213 slides were reviewed by light microscopy. An increased number of metaplastic cells and macrophages, as well as a high leukocyte concentration in post-radiation samples were observed in the majority of the patients. Nuclear and cytoplasmic vacuolization were the most frequent damage observed in the post-radiation group. The alterations of epithelial cells, which are often found in the cervix, were rarely observed in the pulmonary specimens. PMID- 1923632 TI - [Oculopharyngeal muscular dystrophy. Description of a case with involvement of the central nervous system]. AB - A sporadic case of oculopharyngeal muscular dystrophy occurred in a 74-year-old woman is described. High levels of IgA and IgG in the serum, and esophageal smooth muscle involvement are shown. Electromyography of several limb muscles displayed myopathic pattern with giant polyphasic motor unit potentials, suggesting superimposed denervation. The histological examination of peroneus brevis muscle biopsy specimen showed myopathic changes with dystrophic features, associated with neurogenic changes, including atrophic angulated fibers, small group atrophy and type-grouping: concomitant involvement of spinal motor neuron pathway is hypotized, normal values of motor and sensory nerve conduction velocities excluding associated polineuropathy. Furthermore, Somatosensory Evoked Potentials recording revealed bilaterally increased Central Conduction Time. Referring to other similar cases previously reported in the literature, the significance of neurogenic involvement in oculopharyngeal muscular dystrophy is discussed. PMID- 1923633 TI - Malignant sarcomatoid mesothelioma of the pleura: a histological and immunohistological study of a case. AB - The authors describe the case of a 70 year-old asymptomatic female, who showed nodular pleural growths at an occasional chest roentgenogram. Histological examinations and laboratory findings excluded the possibility of an inflammatory granulomatous process, but they did not allow differentiation between malignant sarcomatoid pleural mesothelioma and malignant fibrous histiocytoma. Only at immunohistochemistry was the differential diagnosis made. In fact, the co expression of vimentin and cytokeratins by neoplastic cells, along with their negativity for macrophage markers strongly supported the hypothesis that the neoplastic growth originated from subpleural mesenchymal stem cells. PMID- 1923634 TI - [Malignant melanoma of nasal cavities. Case contributions]. AB - Primitive melanoma of nasal cavities is a rare clinical event. Its pathogenesis is due to the neoplastic development of melanocytes of neuroectodermal origin which are located in the nasal mucosa. Characteristics clinical symptoms are nasal obstruction and recurrent nose-bleeding. In spite of new therapeutic approaches the prognosis of this disease remains severe. No case of primitive malignant melanoma of the nasal cavities has been treated with radiotherapy, according to the authors experience. Sometimes it may be difficult to recognize a cutaneous malignant melanoma because of regression. It may be found after the evidentiation of its recurrences and/or metastasis in different sites. One of the cases here reported came to the authors' attention as ethmoido-frontal metastasis. PMID- 1923635 TI - Anatomopathological study of dementia syndrome linked with an abnormal cerebrospinal fluid flow. Report of literature and personal observations. AB - The authors have analysed the data of the literature to identify the cases of normotensive hydrocephalus that underwent surgery and then died after the operation; some of these patients died over varying periods of time after the operation and the death was due to accidents. It seems that the anatomopathological lesions are less important in cases that benefited from the operation compared with cases that did not present perceptable clinical variations. The authors report the anatomopathological data of four personal cases which, from the clinical point of view, presented the dementia symptom associated in varying degrees to other neurological symptoms such as disturbances of the gait and of the sphincters functions (Adams' triad). All four subjects presented dilatation of the cerebral ventricles without cortical atrophy. From the histological point of view, there was: exfoliation of the ependyma, subependymal gliosis, demyelination of the white periventricular matter and spongiosis; there were no lesions of the meninges, of the cerebral cortex, no vascular alterations, except for those due to age, or stenosis of the aqueduct. The cause of the ventricular dilatation that was responsible for the clinical symptoms was not clear from the histological examination; the value and the significance of the histopathological data obtained and from the data available from the review of the literature are discussed and they point out the fact that many of the lesions encountered seem to be the consequence rather than the cause of the hydrocephalus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1923636 TI - [Prenatal diagnosis of hydrolethalus (Salonen-Herva-Norio syndrome) in a woman with unknown risk: presentation of a case with long survival]. AB - A female infant with hydrolethalus (Salonen-Herva-Norio) syndrome, an autosomal recessive disorder, is reported. This condition was suspected at 26 weeks of gestation by fetal ultrasonographic examination. The pregnancy was complicated by polyhydramnios. The newborn showed hydrocephalus, occipital encephalocele, micrognathia, interventricular defect, hallucal duplication. The patient died at age 5 months and 11 days. PMID- 1923637 TI - [Pterygium of the elbow and post-axial polydactyly on the hands as sign of hereditary onyco-osteodysplasia: 4 familial cases]. AB - Four familial cases of HOOD syndrome are reported. A female newborn showed at birth dysplastic thumb-nails, small nails with triangular lunulae, post-axial polydactylyl at left hand, and hypoplasia of the patella. The mother and the mother's brother showed onycodysplasia, hypoplastic dislocated patella, joint contractures, iliac horns, bilateral post-axial polydactyly on the hand and antecubital pterygium. The patient's sister, born to another man, showed onico osteo dysplasia without pterygium and polydactyly. The variable expressivity of the HODD syndrome and its association with polydactyly, pterygium and nephropathy are discussed. PMID- 1923638 TI - [The pathologist confronting the problem of expertise in the identification of mummies of saints]. PMID- 1923639 TI - Subacute retroperitoneal appendicitis. PMID- 1923640 TI - A pediatrician's view. Conflict of interest. PMID- 1923641 TI - Arrhythmias in the general pediatric population: an overview. PMID- 1923642 TI - Evaluating the child with syncope. AB - Syncope is a multifactorial disorder; however, most pediatric syncopal episodes result from vasodepressor syndrome or the simple faint. A very detailed history and physical examination should indicate the etiology in the majority of cases. Extensive diagnostic studies are rarely necessary. Tilt table testing is a reliable way of identifying individuals predisposed to vasodepressor syncope, and may provide a means of assessing the efficacy of therapeutic interventions in those who require treatment. Treatment for syncope from etiologies other than vasodepressor syndrome is directed at the underlying cause. PMID- 1923643 TI - Sudden death due to cardiovascular disease during childhood. PMID- 1923644 TI - What every pediatrician should know about supraventricular tachycardia. PMID- 1923645 TI - What every pediatrician needs to know about arrhythmias in children who have had cardiac surgery. PMID- 1923646 TI - Transcatheter ablation for pediatric tachyarrhythmias using radiofrequency electrical energy. AB - Radiofrequency ablation is a promising therapeutic option for difficult tachycardias in patients of all ages. Conditions in the pediatric age group that appear most amenable to the technique include accessory pathways and ectopic focus tachycardias, but the list is likely to expand with further experience. Until all long-term risks have been better explored, our institutional policy is to restrict RF ablation to symptomatic children who have failed at least one through trial of pharmacologic control. When a choice must eventually be made between potent antiarrhythmic drugs with variable efficacy and side effects, or an involved and costly surgical procedure, transcatheter ablation would appear to be a reasonable, if not preferred, alternative. PMID- 1923647 TI - Disappearing school nurse services: metamorphosis or endangered species? PMID- 1923648 TI - Temperament in infants and toddlers with cardiac disease. AB - Parental report of temperament in a group of 97 infants and toddlers with cardiac disease revealed differences from healthy children on several temperament dimensions. Increasing disease severity did not correspond with increasingly extreme temperament scores. PMID- 1923649 TI - Parental needs assessment: a design for clinical nurse specialist practice. AB - Parents of children with orthopedic illness or disability were asked to identify their needs and their children's needs for education and support. Their responses were used to shape the clinical nurse specialist's practice. Information about the child's diagnosis and its effect on growth, development, and sexuality were the areas of greatest needs identified by parents in this study. Incorporation of these perceived needs into practice is described. PMID- 1923650 TI - Chronic sorrow: adaptation patterns of parents with chronically ill children. AB - Chronic sorrow is a concept that describes parental psychologic reaction to a child who has special health needs. The term can be applied to all types of chronic disabilities regardless of their degree of severity. The term was conceptualized in the early 1960s, but the research momentum has just recently begun. PMID- 1923651 TI - Case management in inpatient pediatric nursing. AB - Case managed family-centered hospital care can prepare a child and family for transition/continuity to quality home care. One child with complex, chronic, and expensive health care and his family illustrate how this idea can be made a reality. PMID- 1923652 TI - Defibrillation and cardioversion in children. AB - This article overviews the indications for cardioversion or defibrillation by reviewing normal conduction, common arrhythmias, and hemodynamic assessment in children requiring this treatment approach. The procedure for each is outlined in detail. PMID- 1923653 TI - Medicare physician payment reform: implications for nurses and other nonphysician providers. PMID- 1923654 TI - Youth and AIDS project. PMID- 1923655 TI - Health promotion: the new frontier. AB - In a country where many U.S. children live in poverty, do not share equally in health and access to health care, and are at risk for several adolescent problems, health promotion has become the new frontier in health care. The newer approaches to health promotion are discussed. PMID- 1923656 TI - The nurse manager as mentor. AB - Mentoring staff is an essential role of the nurse manager. Developing a workable system and investing the time to carry it through has many positive outcomes for both the manager and the nursing staff. Staff nurses are able to function independently and make decisions concerning their practice as well as their work environment, leaving the nurse manager free to assume a true leadership role. PMID- 1923657 TI - Pediatric management problems: congenital syphilis. PMID- 1923658 TI - A study of the health of pediatric nurses administering cyclosporine A. AB - PURPOSE: To investigate the self-reported health status of pediatric nurses who frequently administer Cyclosporine A (CyA). METHOD: Twenty-two nurses who regularly handle CyA and administer it to children and thirty-one adult medical surgical nurses who do not handle the drug completed a Health Status Questionnaire. Data were analyzed using a chi-square test. FINDINGS: Three symptoms were noted to be statistically more likely to be reported by the CyA exposed group: constipation, tinnitus, and headache. CONCLUSIONS: Although causal relationships cannot be inferred due to sample size and potential confounding variables, implications for nursing practice can be derived. Measures for the protection of the nurse administering the drug should be used to avoid transdermal absorption. PMID- 1923659 TI - Update on sickle cell disease: incidence of addiction and choice of opioid in pain management. PMID- 1923660 TI - Caring: let it begin with me. AB - Caring is the essence of nursing. But only when we care for ourselves can we give to others. PMID- 1923661 TI - The ventilator-assisted child: a case for empowerment. AB - Families are the most valuable resource available to ventilator assisted children. Enabling and empowering families is a nursing intervention that maximizes family strengths and functioning. PMID- 1923662 TI - Evaluation of nasal impedance using the forced oscillation technique in infants. AB - By applying oscillations to the respiratory system through a rigid face mask, the infant-adapted Landser forced oscillation technique measures impedance of the total respiratory system including the nose, at frequencies from 4 to 52 Hz. The present study was aimed at evaluating nasal impedance in infants from consecutive forced oscillation measurements through both nostrils and each nostril separately, using a simple electrical model. In 30 asthmatic infants with varying degrees of nasal obstruction, aged 1-16 months, calculated nasal resistance (Rn) at 24 Hz ranged from 1 to 16 cm H2O.L-1.s. The ratio of Rn to total respiratory system resistance varied between 1 and 48% (mean: 16%). In seven non-asthmatic infants, aged 0-12 months, Rn was between 1 and 11 cm H2O.L-1.s. Nasal patency (evaluated clinically) was correlated with the calculated Rn (P less than 0.05). Rn showed almost no frequency dependence between 24 and 48 Hz as demonstrated by a mean slope of -0.09 +/- 0.08 cm H2O.s2/L for the asthmatic and of -0.08 +/- 0.07 for the non-asthmatic infants. In seven of the asthmatic infants the differences between two Rn determinations at a 45 min interval ranged from -1.7 to 3.8 cm H2O.L-1.s-1 at 24 Hz and from -3.6 to 1.0 at 48 Hz. Changes in Rn did not correlate with changes in total respiratory system resistance (P greater than 0.05). In conclusion, nasal impedance can be approximated from three consecutive measurements through both nostrils and through each nostril separately. PMID- 1923663 TI - Effects of endotracheal tube size and ventilator settings on the mechanics of a test system during intermittent flow ventilation. AB - The effect of varying the size of standard neonatal endotracheal tubes on delivered tidal volumes (VT), resistance (R), dynamic compliance (Cdyn), and resistive work of breathing (WOB) was measured in a test system during intermittent flow ventilation at different ventilator settings. The experiments were performed with a Sechrist infant ventilator connected to a Drager Test Lung via standard neonatal endotracheal tubes. R, inspiratory (Ri), and expiratory resistance (Re) as well as WOB were significantly affected by endotracheal tube size. The calculated difference in Re between endotracheal tubes of 2.5 and 3.5 mm I.D. was 93 cm H2O/L/S (mean value for all studies). Cdyn and VT were also affected by endotracheal tube size. However, although statistically significant differences were found in Cdyn (mean, 0.584 mL/cm H2O and 0.567 mL/cm H2O) and VT (mean, 13.0 mL and 12.7 mL) for the tube sizes 3.5 mm and 2.5 mm I.D., respectively, the absolute numerical differences were small. Also, ventilator settings with respect to the peak inspiratory pressure (PIP) - positive end expiratory pressure (PEEP) difference had a significant influence on Cdyn for both tube sizes. On the other hand, flow and inspiratory time adjustments had no significant effect on ventilatory parameters. Endotracheal tube size and ventilator settings should be considered when comparing the pulmonary function tests in intubated and non-intubated newborn infants. PMID- 1923664 TI - Spontaneous changes in bronchial responsiveness in children and adolescents: an 18-month follow-up. AB - The purpose of this study was to investigate spontaneous changes in bronchial responsiveness to inhaled histamine over a period of 18 months. The first measurements in 495 subjects, 7 to 16 years of age, were made in 1986. Bronchial hyperresponsiveness (BHR), i.e., PC-20 FEV1 less than or equal to 8.0 mg/mL, was found in 79 (16%) individuals, of whom 28 (35%) had symptoms of asthma. Twenty asthmatic and 42 non-asthmatic subjects who had BHR (78%) were re-examined 18 months later. The asthmatics had a modest change in BHR, while in the non asthmatics bronchial response to inhaled histamine and exercise was significantly decreased. In twenty-two subjects (36%) bronchial response was within the normal range; of these 18 were non-asthmatic. Six asthmatics (30%) and two non asthmatics (5%) had an increased BHR at follow-up. Two subjects (5%) developed symptoms of asthma by the time of follow-up, with an unchanged degree of BHR. Sex, age, atopic symptoms, and viral respiratory infections at the first examination were unrelated to changes in bronchial responsiveness. However, changes of BHR in the non-asthmatic subjects were significantly correlated to changes in bronchial response to exercise. Although spontaneous changes in bronchial responsiveness occur in asthmatic, as well as non-asthmatic subjects, asthmatics persistently have hyperresponsive airways. Development of asthma was found to occur among subjects with persistent BHR. PMID- 1923665 TI - Bronchial hyperreactivity in children with Marfan syndrome. AB - Marfan syndrome is known to have pulmonary manifestations such as pneumothorax. There have been few previous studies of pulmonary function tests and none of bronchial hyperreactivity. Therefore, pulmonary function tests were performed in 11 children with Marfan syndrome and 11 normal children. Bronchial responsiveness was tested in ten of the Marfan patients by methacholine challenge test and response to bronchodilator. Because of disproportionate length of legs in Marfan patients, an "ideal" standing height was calculated from sitting height. Pulmonary function tests, as absolute values or as percent predicted based on "ideal" height, were not different in Marfan patients and normals, although a few individual patients had abnormal function (mostly airway obstruction and hyperinflation). Response to methacholine challenge was positive on forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25 and 75% VC (FEF25-75%), and FEF50%, in 37.5%, 60%, and 70% of tests respectively. A significant response to bronchodilators was obtained in 40% of patients as measured by FEV1, in 90% by FEF25-75% and in 100% by FEF50%. Pulmonary function tests after bronchodilator were significantly higher when compared with values before the bronchodilator as well as with the baseline before methacholine. Therefore, most if not all patients with Marfan syndrome had hyperreactive airways in this relatively small group of patients. Even though only one patient had a diagnosis of asthma, six more had subtle symptoms. It is concluded that tests for bronchial hyperreactivity could be part of the routine investigation in Marfan syndrome. Further studies on larger numbers of patients are still needed. PMID- 1923666 TI - Clinical observations on lower respiratory tract infections with special reference to serum IgE levels. AB - To examine if the occurrence of wheezing among children with lower respiratory tract infections is associated with atopic predisposition, serum levels of IgE were determined for groups of children with or without wheezing, during infection with Mycoplasma pneumoniae or respiratory syncytial virus (RSV). In M. pneumoniae infection, more than 60% of wheezy children over 2 years of age showed a high IgE level (200 IU/mL or more), while IgE levels were less than 200 IU/mL in 73% of non-wheezy children. In RSV infection, the incidence of high IgE levels among wheezy children was nearly double that of non-wheezy children, although the difference was not significant. These results suggest that in children an allergic disposition is involved in the occurrence of wheezing during the course of lower respiratory tract infections. PMID- 1923667 TI - Pulmonary function in newborns after repair of congenital diaphragmatic hernia. AB - Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia that limits survival, but the nature and extent of pulmonary dysfunction in neonates with CDH have not been studied. We performed pulmonary function tests (PFTs) in eight intubated infants who survived neonatal repair of CDH (wt, 3.33 +/- 0.15 kg; age, 20.1 +/- 2.7 d; mean +/- S.E.M.). PFTs obtained from six full term infants (wt, 3.56 +/- 0.15 kg; age, 25.0 +/- 3.3 d) with no respiratory illness served as controls. The deflation flow-volume curve technique produced maximum expiratory flow-volume (MEFV) curves, giving reproducible measurements of forced vital capacity (FVC) and maximal expiratory flow at 25% of FVC (MEF25). Respiratory system compliance (Crs) and resistance (Rrs) were obtained with a modified passive mechanics technique. In seven of eight infants PFTs were repeated after nebulized bronchodilator (0.1% isoetharine). In neonates surviving CDH repair, as compared to those with normal lung function, FVC was significantly reduced (20.78 +/- 3.32 vs. 39.83 +/- 3.30 mL.kg-1, P less than 0.05). MEF25 was also markedly reduced (20.78 +/- 3.32 vs. 39.83 +/- 3.30 mL.kg-1.s-1, P less than 0.05), indicating lower airway obstruction. After administration of nebulized bronchodilator, PFTs showed significant increases from control values in both FVC (15.9%) and MEF25 (200%) without changes in Crs and Rrs. These findings indicate that neonates with CDH have restrictive lung defects, reflecting hypoplasia. After surgical repair and mechanical ventilation airway reactivity develops, primarily in smaller airways, and this may complicate the postoperative course. PMID- 1923668 TI - Subacute effects of respiratory syncytial virus infection on lung function in lambs. AB - We examined the effects of ovine respiratory syncytial virus (RSV) infection on lung mechanics, lung histology, and airway reactivity in lambs. Nine lambs were inoculated with ovine RSV and seven control lambs with normal saline or viral media. Serum neutralization titers were obtained prior to and 3 weeks post inoculation (PI). Open lung biopsies were performed 1 and 3 weeks PI. Lung mechanics including dynamic compliance (Cdyn), resistance of the lung (RL), and functional residual capacity (FRC) were measured 2 and 6 weeks PI using a plethysmograph. Airway reactivity to aerosolized carbachol, citric acid, and histamine was determined 2 and 6 weeks PI. Most RSV and control lambs were asymptomatic after inoculation. Control lambs had significantly greater average daily weight gain by the third week after inoculation. Seven RSV lambs tested had a fourfold or greater rise in serum neutralization titers, while two control lambs had a fourfold increase. At 2 weeks PI, RSV lambs had significantly lower FRC and higher RL. At 6 weeks RL remained significantly elevated in the RSV lambs. Airway reactivity was not increased in the RSV group. This animal model is useful for studying the effects of RSV infection on lung growth and lung function over time. PMID- 1923669 TI - Surfactant replacement therapy. PMID- 1923670 TI - Longitudinal changes in lung function during the first three years of premature infants with moderate to severe bronchopulmonary dysplasia. AB - Bronchopulmonary dysplasia (BPD) is a chronic obstructive pulmonary disease of prematurely born infants following prolonged mechanical ventilation and oxygen therapy. Developmental changes in pulmonary function of children with BPD during their early years have been difficult to study. We longitudinally studied maximal expiratory flow-volume curves by the forced deflation technique in 11 infants who had previous tracheostomy with moderate to severe BPD. Patients were classified into: those who were mechanically ventilated for less than 5 months (Group A), and those who were ventilated for 10 or more months (Group B). At 6 months of age, forced vital capacity (FVC) was 28.1 and 25.5 mL/kg in Group A and B, respectively, significantly less than normal (41.8 mL/kg). The maximum expiratory flow at 25% FVC (MEF25) at 6 months of age was 6.9 and 8.1 mL.kg-1.s-1 in Group A and B, respectively, (predicted value, 39.2 mL.kg-1.s-1). FVC reached the normal range by 12 months of age in Group A, but remained lower until 36 months of age in Group B. MEF25 gradually increased in Group A, reaching 18.0 mL.kg-1.s-1 at 36 months of age, whereas in Group B it was severely decreased at the same age (3.5 mL.kg-1.s-1). More than 75% of the patients had airway hyperreactivity at all ages. We have demonstrated that in patients with moderate to severe BPD, vital capacity is moderately decreased, but catches up to normal levels by 36 months of age. In contrast, severe lower airway obstruction persists in all infants, although in those with moderate BPD gradual improvement is seen. These findings suggest that in BPD neither obstruction of the smaller intrathoracic airways nor bronchial hyperreactivity resolves during the first 3 years of life. PMID- 1923671 TI - Ultrafast computerized tomography of the chest in cystic fibrosis: a new scoring system. AB - Assessing the presence and severity of bronchiectasis (BR) and mucoid impaction (MI) of the airways in cystic fibrosis (CF) is difficult by non-invasive methods. We hypothesized that scoring ultrafast computerized tomograms (UFCT) of the chest for BR and MI could be useful in detecting early lung changes in 28 patients with CF. To do this, UFCT scores were compared to established clinical and chest X-ray (CXR) scores. Results showed that UFCT scores correlated highly with clinical (r = 0.88) and CXR (r = 0.93) scores, and several pulmonary function tests. Regression analysis indicated that BR influenced clinical and CXR scores more than MI. Both BR and MI were found in all areas of the lungs without a major propensity for one region, although there was significantly more BR in the right upper lobe than the right lower lobe. In patients with CXR score greater than or equal to 21 BR was present in 8/9 and MI in 3/9, while in those with CXR score less than 21 UFCT showed BR in 19/19 and MI in 17/19. We conclude: 1) scored UFCTs correlate well with CXR and clinical scores; 2) BR influences clinical and CXR scores more than MI; 3) UFCTs detect BR and MI in CF patients with minimal evidence of pulmonary disease; and 4) CXR scores less than 21 reflect the presence of both BR and MI. PMID- 1923672 TI - Bacterial tracheitis as a complication of endotracheal intubation. PMID- 1923673 TI - A pediatrician in the Persian Gulf War: a reserve officer's view. PMID- 1923674 TI - A pediatrician in the Persian Gulf War: a career officer's view. PMID- 1923675 TI - Use of routine urinalysis in making a presumptive diagnosis of urinary tract infection in children. PMID- 1923676 TI - Urine screen for bacteriuria in symptomatic pediatric outpatients. AB - A retrospective review of 1019 symptomatic pediatric outpatients compared urine dipstick including leukocyte esterase and nitrite to semiquantitative Gram stained smear of uncentrifuged urine for the identification of specimens that contained greater than or equal to 10(5) organisms/ml as determined by semiquantitative urine cultures. The Gram-stained smear was slightly more sensitive than the dipstick; 97.6% (any microorganisms seen or greater than or equal to 2 organisms/oil immersion field) vs. 90.2% (either leukocyte esterase- or nitrite-positive). The negative predictive value of both screening methods was excellent (99.9 and 99.6%, respectively). The predictive value of a positive screen was low for both methods although the predictive value of a positive screen of the Gram-stained smear did reach 63% when there were greater than or equal to 5 organisms/oil immersion field. Neither method of urine screen should substitute for a urine culture in the symptomatic outpatient. However, the urine dipstick test is a reasonable alternative to a Gram-stained smear for initial patient assessment. PMID- 1923677 TI - Incidence of intestinal parasitic disease in an acquired immunodeficiency syndrome day-care center. AB - In June, 1986, the Bronx Municipal Hospital Center opened an acquired immunodeficiency syndrome day-care center to provide a quality educational experience for children infected with the human immunodeficiency virus. A major concern was the possibility of increasing secondary infections among these immunocompromised children by placing them in a group environment. One particular worry was intestinal parasitic disease, a serious public health problem in day care centers throughout the United States. To minimize the risk of parasitic infections, scrupulous hygienic and monitoring procedures were instituted at the acquired immunodeficiency syndrome day-care center. This study reports the incidence of intestinal parasitic disease at the acquired immunodeficiency syndrome day-care center during its first 40 months of operation, encompassing 669 child-months of enrollment, with 131 stool specimens examined for ova and parasites. There were 2 cases of parasitic infection: Entamoeba histolytica in an asymptomatic 6-year-old and Giardia intestinalis in a 7-year-old with diarrhea. In neither case was there any secondary spread. None of the 15 children in diapers had a positive specimen, and we found no Cryptosporidium. Our experience suggests that with appropriate precautions human immunodeficiency virus-infected children can participate in a group day-care program without excessive risk for parasitic disease. Strict adherence to hygienic procedures may also decrease the risk of intestinal parasitic disease among healthy children attending day-care centers. PMID- 1923678 TI - Extrapulmonary cryptococcosis in children with acquired immunodeficiency syndrome. AB - There is a paucity of published information available on extrapulmonary cryptococcosis (EC) in children infected with human immunodeficiency virus, the etiologic agent of the acquired immunodeficiency syndrome. We surveyed investigators in pediatric acquired immunodeficiency syndrome around the country regarding their experience with EC. Investigators from 33 (87%) of 38 institutions responded and information on 13 patients from 11 institutions was analyzed. EC was the acquired immunodeficiency syndrome indicator disease in 9 (69%) of 13 patients. Median age was 8 years with a range of 2 to 17 years. Human immunodeficiency virus risk factors were transfusion (5 patients), hemophilia (4 patients) and perinatal exposure (4 patients). Meningitis, seen in 62% of patients, was the most common clinical manifestation. Although 2 patients with fulminant disease died before therapy was started, 10 (91%) of 11 had a clinical response to amphotericin B with or without flucytosine. Our study indicates a spectrum of EC in pediatric human immunodeficiency virus infection ranging from fulminant, fatal fungemia to chronic meningitis and fever of unknown origin. Cryptococcosis was generally not the cause of death in patients who initially responded to amphotericin B therapy. Optimal antifungal therapy, including the role of fluconazole, warrants further study. PMID- 1923679 TI - Diminished IgG, but not complement C3 or C4 or factor B, precedes nosocomial bacterial sepsis in very low birth weight neonates. AB - The significance of low serum IgG and complement proteins in very low birth weight (VLBW; less than 1500 g) neonates is not known. Therefore serum IgG, C3, C4 and Factor B were quantitated weekly by rate nephelometry in 15 VLBW neonates who developed proven nosocomial bacterial or candidal sepsis (Group A) and 27 VLBW neonates who did not develop sepsis (Group B). In the first week of life the serum IgG of neonates in Group A was 295 +/- 33 mg/dl (mean +/- SEM) and in Group B it was 440 +/- 21 mg/dl (P less than 0.01). In the second week, the IgG of Group A was 270 +/- 32 mg/dl and that of Group B was 473 +/- 38 mg/dl (P less than 0.01). If the IgG was less than 350 mg/dl in the first week or less than 230 mg/dl in the second week, the relative risk of acquiring sepsis was greater than or equal to 5 (95% confidence interval in the first week, 1.7 to 11.2). The serum IgG was measured before the onset of sepsis in 14 of the 15 neonates in Group A. In the week before sepsis the IgG of the 14 neonates was less than 440 mg/dl (range, 45 to 433 mg/dl) in all cases, was below the mean IgG of Group B in 12 of 14 cases (P = 0.006 vs. Group B) and was greater than 2 SD below the mean IgG of Group B in 4 of 14 cases (P = 0.0003 vs. Group B).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1923680 TI - Transmission of Salmonella worthington by oropharyngeal suction in hospital neonatal unit. AB - An outbreak of Salmonella worthington infection in a neonatal unit occurred in a pediatric ward of Holy Family Hospital, Rawalpindi, Pakistan. The index case was a prematurely born male child from whose clinical specimens S. worthington was recovered. After this finding 40 infants kept in that nursery were included in an investigation. Major symptoms were diarrhea, septicemia and jaundice. Three developed meningitis. Disease morbidity rate was 45% and mortality occurred in 16.6% of the total positive cases. The source of infection was traced to a contaminated rubber tubing of a suction apparatus which was used for oropharyngeal suction of the babies. S. worthington was recovered from the clinical specimens of all 18 babies who received suction. Multiple drug resistance of these S. worthington strains was found. PMID- 1923681 TI - Assessment of a clinical scoring system for detection of immunodeficiency in children with recurrent infections. AB - From January, 1982, to July, 1990, 51 children with recurrent infections were investigated for immunodeficiency in this department by testing neutrophil function, lymphocyte subsets and serum immunoglobulin and complement concentrations. The prevalence of immune dysfunction within the group was 39% (20 of 51). A previously described clinical scoring system, which aims to identify children with a history of recurrent infection who merit investigation for immunodeficiency was also applied to all 51 children. The scoring system identified only 55% (11 of 20) of those with laboratory-proved immunodeficiency and had a false negative rate of 45% (9 of 20). This latter group included 2 children with severe combined immunodeficiency and 1 with hypogammaglobulinemia, diagnoses that one cannot afford to miss. The system was not sufficiently sensitive to be of use in deciding which child to test for immunodeficiency. PMID- 1923682 TI - Kingella kingae infection in children: ten cases and a review of the literature. PMID- 1923683 TI - Medical management of newborns and infants born to human immunodeficiency virus seropositive mothers. PMID- 1923684 TI - Effect of chemoprophylaxis on the meningococcal carrier state after systemic infection. PMID- 1923685 TI - Urticaria in patients with hepatitis A virus infection. PMID- 1923686 TI - Recurrent penicillin-resistant pneumococcal meningitis after chloramphenicol therapy. PMID- 1923687 TI - Unilateral pneumonia in an infant. PMID- 1923688 TI - Reported infectious diseases in the USSR and United States. PMID- 1923689 TI - Significance of Gardnerella vaginalis in a prepubertal female. PMID- 1923690 TI - Risk of toothbrushes in the transmission of respiratory infections. PMID- 1923691 TI - Early development of the neutral theory. PMID- 1923692 TI - The politics of prolapse: a revisionist approach to disorders of the pelvic floor in women. PMID- 1923693 TI - What are little boys made of? The never-ending search for sex selection techniques. PMID- 1923694 TI - Ageing and disease: proteins as the molecular link. PMID- 1923695 TI - Humphry Davy's contribution to the introduction of anesthesia: a new perspective. PMID- 1923696 TI - The discovery of new diseases by utilizing laboratory data for clinical research. PMID- 1923697 TI - The rise, decline, and fall of LSD. PMID- 1923698 TI - Fertility decline in Europe, 1875-1913. Was zinc deficiency the cause? PMID- 1923699 TI - PVC as pharmaceutical packaging material. A literature survey with special emphasis on plasticized PVC bags. AB - In this report the state of the art with respect to PVC as pharmaceutical packaging material is described. A general introduction into the applications of PVC is followed by a description of its production process. The metabolic effects of the monomer of PVC, vinyl chloride and of the most commonly used plasticizer diethylhexylphthalate are mentioned. Special attention is given to the pharmaceutical properties of plasticized PVC bags in comparison to other plastics and the environmental aspects of waste PVC disposal. Although there are emotional and political queries regarding the future use of PVC as a (pharmaceutical) packaging material, we conclude that there is no scientific justification for a total or partial ban of PVC. PVC will remain a fact of life as a cheap, versatile, high-performance and well-investigated plastic material for medical and pharmaceutical applications, to be replaced by newer plastics only for certain well-defined indications where the requirements of the plastic to be used are so specific that it will economically and technically be justified to use another polymer. Community and hospital pharmacists have to be prepared for a role in intake of waste plastic disposables, probably against deposit money, in order to fulfil the logistics needed for recycling. PMID- 1923700 TI - Allergic contact dermatitis caused by naturally occurring quinones. AB - Quinones play a major role in allergic contact dermatitis caused by plants. The principal allergens are benzoquinones or naphthoquinones but also compounds, such as catechols and other phenolic or flavonoid compounds, which are bioconverted into ortho-quinones or para-quinones. The high electrophilic reactivity of these compounds toward nucleophilic residues of proteins associated with lipophilic properties may explain that they are strong sensitizers. The more important allergens are reported and their structure-activity relationship is discussed. PMID- 1923701 TI - Bioreductive activation of quinones: a mixed blessing. AB - Quinones can be metabolized by various routes: substitution or reductive addition with nucleophilic compounds (mainly glutathione and protein thiol groups), one electron reduction (mainly by NADPH: cytochrome P-450 reductase) and two-electron reduction (by D,T-diaphorase). During reduction semiquinone radicals and hydroquinones are formed, which can transfer electrons to molecular oxygen, resulting in the formation of reactive oxygen intermediates and back-formation of the parent quinone (redox cycling). Reaction of semiquinones and reactive oxygen intermediates with DNA and other macromolecules can lead to acute cytotoxicity and/or to mutagenicity and carcinogenicity. The enhanced DNA-alkylating properties of certain hydroquinones are exploited in the bioreductive alkylating quinones. Acute cytotoxicity of quinones appears to be related to glutathione depletion and to interaction with mitochondria and subsequent disturbance of cellular energy homoeostasis and calcium homoeostasis. These effects can to a certain extent be predicted from the electron-withdrawing and electron-donating effects of the substituents on the quinone nucleus of the molecule. Prediction of cytostatic potential remains much more complicated, because reduction of the quinones and the reactivity of the reduction products with DNA are modulated by the prevailing oxygen tension and by the prevalence of reducing enzymes in tumour cells. PMID- 1923702 TI - Immunomodulation by quinones. A model for the use of quinones in the treatment of inflammation. AB - The therapeutic application of quinones in areas other than oncology, such as in chronic inflammation, has been proposed. However, because of the adverse side effects on the function and vitality of almost all investigated cell types the therapeutical margin is small. The thiol-conjugating capacity of quinones may, however, be applied to reduce the tissue-damaging effects of stimulated neutrophils. In this paper evidence is provided that particular phenols may be used as precursor molecules of quinones. Secretory products from stimulated neutrophils can convert such phenols into quinones. As under normal conditions stimulated neutrophils are present only in inflamed tissues, quinones will be formed only at these sites. PMID- 1923703 TI - Microbiological aspects of heat sterilization of drugs. III. Heat resistance of spore-forming bacteria, isolated from large-volume parenterals. AB - In order to calculate the minimum sterilization process conditions to obtain the generally accepted sterility level (less than 1.10(-6) probability of microbial survival), we determined the bioburden and its heat resistance of 500 ml large volume parenteral bottles over a period of 5 years. For the bioburden determination 1,832 bottles were examined by the membrane filtration method. Mean bioburden was 9.36 colony-forming units/bottle. Of the colony-forming units isolated 118 were heat resistant (0.69%). These were spore-forming Bacillus species. Of the isolated Bacillus species heat resistance was determined in 5% glucose, 0.9% sodium chloride and 8% amino acids solution. D values greater than 1 min at 105 degrees C were found for 2, 5 and 4 different Bacillus species in glucose 5%, sodium chloride 0.9% and amino acids 8%, respectively. 2 Bacillus species showed a D value over 2 min at 105 degrees C in all three media. D values at 110 degrees C in sodium chloride 0.9% for these 2 Bacillus species were 1.8 and 2.6 min and in amino acids 8% 0.9 and 1.7 min, respectively. The minimum sterilization process time at 110 degrees C, calculated with the experimentally determined bioburden and D values is less than 25 min. When introducing reduced exposure times/temperatures, each individual manufacturer should assess the bioburden. The time-consuming determination of the heat resistance of bioburden isolates is not always necessary. By dividing the isolated colony-forming units in a 'heat-resistant' group and a 'not-heat-resistant' group, changing from standard overkill sterilization procedures to processes with lower F0 values is possible. PMID- 1923704 TI - Small-scale preparations in Sweden. Extemporaneous preparations and stock preparations at eleven community pharmacies. AB - Small-scale preparations, i.e. non-registered drugs that are extemporaneously prepared for each patient or made in larger batches for stock keeping, form a small but important group of drugs, especially for patients with rare diseases or allergies. Small-scale preparations are not included in the otherwise comprehensive statistics compiled by the National Corporation of Swedish Pharmacies and this makes knowledge of the use of these drugs limited. The occurrence of small-scale preparations was studied at eleven community pharmacies over a three-year period (1987-1989) by analysis of the orders from the pharmacies to the four production units of the National Corporation of Swedish Pharmacies in the first quarter of each study year. The number of small-scale preparations dispensed were compared with the total sales of drugs at each pharmacy. The proportion of small-scale preparations in the total drug sales was about 1.5% throughout the study period, but there were fluctuations over time at the individual pharmacies. The most common dosage forms were creams, liniments and mixtures. Dermatological drugs in different dosage forms were the most frequent (almost 50%). This was probably because of the necessity for a great variety of different strengths among these drugs. PMID- 1923706 TI - Abstracts of papers. Pharmacological meeting. Utrecht (The Netherlands), 6 November and 4 December 1991. PMID- 1923705 TI - Pharmacokinetics of nicomorphine and its metabolites in man after epidural administration. AB - In ten patients who received an epidural injection of 15 mg of nicomorphine, the compound was relatively slowly released from the epidural space and was found in plasma for approximately 1.5 h. Nicomorphine is relatively slowly metabolized into 6-nicotinoylmorphine and morphine. The rate of release is patient-dependent. The relative AUC values are 15.3% for nicomorphine, 23.9% for 6 nicotinoylmorphine and 60.8% for morphine. The mean clinical effect lasts for 18.2 +/- 10.1 h. PMID- 1923707 TI - Abstracts of papers. Age and pharmacotherapy. 20th European Symposium on Clinical Pharmacy. Poznan (Poland), 23-26 October 1991. PMID- 1923708 TI - Abstracts of papers. Bi-annual scientific meeting of the Dutch Society of Hospital Pharmacists. Maastricht (The Netherlands), 13-14 September 1991. PMID- 1923709 TI - The treatment of longitudinal radial deficiency. AB - Absence of the radius is the commonest of the longitudinal deficiencies but is itself quite an unusual congenital anomaly. No one surgeon is likely to encounter the condition more than once or twice in a career and there is a strong case for congenital upper limb conditions to be collected into special clinics. The pathology and methods of surgical treatment are reviewed. It is a difficult condition to treat but there is no doubt that function and appearance can be improved (Pulvertaft, 1973). Pollicisation of the index finger should be considered and can often greatly improve the function. PMID- 1923710 TI - The treatment of longitudinal ulnar deficiency. AB - Longitudinal ulnar deficiency, whose detailed anatomy is varied, is often accompanied by other abnormalities and appears as part of several syndromes. The history of its classification is reviewed, and the treatments, which have been offered, described. Follow-up of a series shows that the function achieved is good and is optimised by aids, occupational therapy and some hand surgical procedures. The more elaborate surgical reconstructions are unlikely to be beneficial. PMID- 1923711 TI - The surgical treatment of congenital hand deficiency. PMID- 1923712 TI - The prosthetic treatment of lower limb deficiency. AB - The prosthesis required for a child with a transverse deficiency whilst a simple version of that appropriate for the adult follows the same principles. The child with a longitudinal deficiency may require an extension, or orthoprosthesis and this may be combined with surgical reconstruction. The principles, technique of measurement and fabrication methods using both traditional and modern composites are described. PMID- 1923713 TI - The classification and treatment of proximal femoral deficiencies. AB - After a review of previous classifications the authors suggest that cases of congenital longitudinal deficiency of the femur fall into one of two groups, each with specific features. The treatment alternatives and their indications are discussed in detail and a treatment plan suggested. PMID- 1923714 TI - The surgical treatment of partial tibial deficiency and ankle diastasis. AB - In cases of congenital partial tibial aplasia or so-called diastases of the lower leg, very good results are to be expected from tibia/fibula fusion in association with a repositioning of the foot. Form and function of the limb are significantly improved, with ortho-prosthetic fitting being considerably facilitated. PMID- 1923715 TI - Fibular deficiency and the indications for Syme's amputation. AB - Recent literature on the subject is reviewed, and the role of Syme's amputation, reconstructive surgery and prosthetic management is discussed in relation to the severity of the condition. Amputation, which should be performed between 18 months and two years old is specifically recommended for total fibula absence with ankle instability. The operative technique is detailed. PMID- 1923716 TI - Reconstructive surgery for fibular deficiency. AB - Three types of fibular deficiency are described which determine the nature of the surgery and prosthesis required. The surgical management of 50 patients who had a total of 103 operations is described. PMID- 1923717 TI - The care of the limb deficient child in Australia. AB - The incidence of limb deficiency is given as is the prevalence of prosthetic use in Australia. The organisation of clinics and the Free Limb Scheme is described and its effects discussed. PMID- 1923718 TI - The care of the limb deficient child in India. AB - The problem of treating limb deficient children in India is compounded by many factors, social, cultural and economic. Few attend early and most therefore manage without prosthetic care. PMID- 1923719 TI - The care of the limb deficient child in Japan. PMID- 1923720 TI - The care of the limb deficient child in north Africa. AB - The surgical and prosthetic treatment of longitudinal lower limb deficiency is described and discussed, in the light of cultural and social requirements. Those with upper limb deficiencies are not fitted with prostheses. PMID- 1923721 TI - The care of the limb deficient child in Venezuela. AB - An overview of the situation in Venezuela is made by sampling the cases of congenital limb deficiency treated at the Hospital San Juan de Dios in Caracas from 1961-1989. The major longitudinal deficiencies are analysed. The socioeconomic situation of the patients is of most importance being the cause of final decisions in relation to surgery, the ordering of prosthesis and orthosis, supplied mainly by the Venezuelan Institute of Social Security (IVSS), the maintenance of these items and the possibility of travelling to the hospital for diagnosis, treatment and follow-up. All these transform the situation from a medical problem into a socio-economic problem typical of a third world country. PMID- 1923722 TI - The function and operation of a parent support association. AB - The use of a parent support organisation and its responsibilities and limitations are described. The difference between a parent support organisation and an association of limb deficient children is discussed. PMID- 1923723 TI - A personal experience. AB - David Bailey, who is 14 years old, has a left transverse total forearm deficiency and bilateral longitudinal femur partial deficiencies. The latter fall into Torode and Gillespie's Group I, with marked femoral shortening. A wedge osteotomy was performed for his gross right coxa vara, which was successful, but an intractable fixed flexion deformity of the right knee led eventually to a knee disarticulation being performed. PMID- 1923724 TI - The ISO/ISPO classification of congenital limb deficiency. AB - This classification originally produced by the ISPO "Kay" Committee in 1973, has now with minor modifications, become an International Standard (ISO 8548-1: 1989). It is limited to those deficiencies which are failures of formation and describes them on anatomical and radiological bases only. All are divided into transverse and longitudinal, and use simple terms and descriptors. PMID- 1923725 TI - Heredity and dysmorphic syndromes in congenital limb deficiencies. AB - Isolated limb deficiencies are usually sporadic occurrences. However, if they are associated with other abnormalities or a family history, the risk to future pregnancies may be as high as 50%. A thorough history, examination and investigation of the baby as well as the parents is essential before assessing this recurrence risk. The syndromes associated with limb deficiencies are presented. PMID- 1923726 TI - The management of the limb deficient child and its family. AB - The team approach is considered the optimal to the care of the limb deficient child. A coordinated programme utilising the expertise of experienced personnel and taking into consideration the developmental needs of the child will allow the child to grow and function as normally as possible. The goal of the team is to assist the patient to become a productive, self-sufficient member of society. PMID- 1923727 TI - The prosthetic treatment of upper limb deficiency. AB - The provision of prostheses for children with upper limb deficiency starts at an early age. The roles of the occupational therapist and prosthetist in this programme are described. Casting and fitting techniques applicable to transverse forearm loss and aspects of myoelectric hand prostheses are included. An outline of training methods as related to both parent and child is explained. Higher levels of limb deficiency are covered briefly and the use of alternative methods of electric hand control is included. Finally, a brief summary of distal deficiency is discussed. PMID- 1923728 TI - Structured training of children fitted with myoelectric prostheses. AB - This paper presents an occupational therapy method for training children fitted with myoelectric prostheses. It is based upon a structured way of describing the accomplishments of a child fitted with a myoelectric prosthesis, called the Skill Index Ranking Scale (SIRS). By using the SIRS when designing the training session, the therapist can progressively increase the demands presented to the child. Furthermore, the SIRS facilitates for the therapist the documentation and communication of the childs ability with the myoelectric prosthesis. PMID- 1923729 TI - The use of electric elbows in the rehabilitation of children with upper limb deficiencies. AB - For those with levels of loss above the elbow, the normal prescription choice is now considered to be the use of an electric elbow combined with a myoelectric hand using a single site three state control. The lightweight VASI unit controlled by a harness mounted switch is mounted in a prosthesis the socket of which is total contact, and allows improved power transfer. PMID- 1923730 TI - The stump capping procedure to prevent or treat terminal osseous overgrowth. AB - Terminal overgrowth in transverse deficiencies and in amputations, particularly of the humerus and tibia necessitate serial trimming procedures or re-amputation. Capping using an autogenous bone graft or a titanium and polyethylene endoprosthetic cap provides a satisfactory way of avoiding these re-amputations and allowing end-bearing. PMID- 1923731 TI - Learning style preferences by nursing students. PMID- 1923732 TI - Position Statement on the HIV positive registered nurse. PMID- 1923733 TI - Barrier to condom use identified. PMID- 1923734 TI - ANA opposes mandatory HIV testing. PMID- 1923735 TI - Traveling with friends to visit friends. PMID- 1923737 TI - [Risk of HIV in health services?]. PMID- 1923736 TI - New Medicare coverage of nurse practitioner services in nursing facilities. PMID- 1923739 TI - [Finland's attitude to HIV-infection--a 5-year follow-up study]. AB - Changes in the Finns' knowledge of attitudes to and behaviour in connection with HIV infection between 1986 and 1990 were studied. In 1986, 1013 Finns aged 15 to 64 years were chosen at random from the entire population. During the years 1987 1990, about 1900 more Finns were selected in the same way. All subjects were interviewed at home or by telephone, using a structured questionnaire. Knowledge of modes of transmission of HIV infection, of the test method, and of where testing could be done was good. Knowledge of the proven modes of transmission of HIV improved significantly between 1986 and 1990. Misconceptions decreased over the same period. Many Finns changed their behaviour because of the risk of HIV infection during this period. For example, 75 per cent informed themselves about AIDS, 9 per cent increased their use of condoms, and 6 per cent had themselves tested for HIV. The improvement in knowledge of AIDS, the change in behaviour, and decrease in the number of cases of HIV detected in Finland, all occurred after widespread public discussion and nationwide information campaigns. It was therefore concluded that the knowledge of AIDS increased, and the behaviour of the general public changed as a result of providing information. PMID- 1923740 TI - [Heterosexual infection increased in Denmark]. PMID- 1923738 TI - [HIV/AIDS in Eastern Europe epidemiology, prevention and control]. AB - During recent years, in the eight countries of Eastern Europe (Albania, Bulgaria, The Czech-o-Slovakia, Hungary, Poland, Romania, USSR and Yugoslavia), the health situation has stagnated, or, in some areas, even deteriorated. The development trend of some common diseases and of risk factors emphasizes the uneven health development in Eastern Europe, and the increasing gap between health conditions in Eastern and Western Europe. The spread of the Human Immunodeficiency Virus (HIV) started relatively late in Eastern Europe, but has recently increased markedly in several countries. Partly as a result of the rapidly changing social and economic conditions in Eastern European countries, a dynamic expansion of this epidemic is taking place, and a sharp increase in the number of people infected with HIV may be expected over the next years. Intensive cooperation between WHO and the individual countries in Eastern Europe has been initiated in the fields of health promotion and disease prevention. One element of this cooperation has been to produce comprehensive National Aids Control Programmes in all these countries. External support of the Aids Control Programmes in Eastern Europe can help to prevent a rapid development of the HIV epidemic, and, in addition, have a catalytic effect on the development of all aspects of the primary health service in these countries. PMID- 1923741 TI - [Coagulase-negative staphylococci--problem bacteria in the hospital. Identification and resistance status]. AB - 131 coagulase-negative staphylococci (CNS) of clinical significance were investigated during the period 1989-1990 in Northern Norway. The staphylococci were isolated from blood cultures (68/131, 51.9 per cent), vascular catheters (6/131), patients with osteomyelitis (13/131), postoperative and other wounds (15/131) and urinary tract infections (29/131). The staphylococci were mostly from hospitalized patients (114/131). Vitek's GPI and Rosco's Staph-zym both gave a primarily correct identification in 95 per cent of the cases. S epidermidis was the predominant species (96/131; 73.3 per cent). Methicillin resistance (MR) was found in 30.5 per cent (40/131) of all CNS and in 35.4 per cent (34/96) of S epidermidis. Methicillin resistant S epidermidis isolates were usually resistant to gentamicin (25/34, 73.5 per cent). S haemolyticus was the most resistant species with MR in 5/7 strains. MR imply resistance to all beta-lactam antibiotics, including imipenem. Among S epidermidis, an increased MR from 10 per cent in 1987 to 35.4 per cent in 1989-1990 was observed. All strains were sensitive to vancomycin and rifampicin. PMID- 1923743 TI - Accidents claim young victims in the US. PMID- 1923742 TI - [The prestige of illnesses and medical specialties]. AB - Diseases and medical specialties differ as regards social prestige. Samples of experienced physicians, medical students at two different levels, and other health professions were asked to rate 38 diseases and 22 medical specialties and subspecialties by prestige. The measured differences in prestige were substantial. Among the diseases, myocardial infarction, leukemia and brain tumour were ranked highest, whereas fibrositis, liver cirrhosis and depressive neurosis came lowest. Among the specialties, neurosurgery, cardiology and thorax surgery were top ranked, while geriatrics, dermatology and psychiatry had lowest prestige. The differences between the ratings of the doctors, medical students and representatives of other health professions were small. This result indicates that the resulting scales of prestige of diseases and specialties, besides being of interest in themselves, can be used for purposes of analysis, e.g. in analysis of the allocation of economic resources in the health services. PMID- 1923744 TI - [When should physicians refrain from treatment?]. AB - The Swedish board of health and welfare has proposed guidelines for the treatment of patients in the last stage of life. The guidelines correspond to those in the Appelton document. It is stated that the doctor may reject or not use extensive life-prolonging treatment to patients in the very last stage of life if there is no hope for them to be better. It is also stated that the patients have the right of good care as long as they live. PMID- 1923745 TI - [Trace elements and hormones]. AB - The relationship between trace elements and health was discussed at The Seventh International symposium on Trace Elements in Man and Animals in Dubrovnik in May 1990. The following five elements were discussed: aluminium, copper, chromium, selenium and zinc. PMID- 1923746 TI - [Education in geriatrics for physicians in Scandinavian countries]. PMID- 1923747 TI - [Classification of diseases--is a systematic approach only possible at the expense of applicability?]. AB - Classification of diseases is a practical tool in clinical and scientific medicine, but it is not free of problems. Using for example WHO's classification of diseases as a starting point, an example of the problems is given in the article, with reference to both methodological and philosophical points of view. It is suggested that pragmatic taxonomies with several dimensions, which would be useful for more than just a handful of clinicians, should be created. Subsequently, this type of classification can be revised in accordance with theoretical ideal requirements and considerations. PMID- 1923748 TI - Peri-implant maintenance. PMID- 1923749 TI - Diabetes--a risk factor for periodontitis? PMID- 1923750 TI - Team compensation, personal power, and prosperity for the 1990's private practice. PMID- 1923751 TI - Haemophilia A: database of nucleotide substitutions, deletions, insertions and rearrangements of the factor VIII gene. AB - Mutations at the factor VIII gene locus causing Haemophilia A have now been identified in many patients from many ethnic groups. Earlier studies used biased methods which detected repetitive mutations at a few CG dinucleotides. More recently rapid gene scanning methods have uncovered an extreme diversity of mutations. Over 80 different point mutations, 6 insertions, 7 small deletions, and 60 large deletions have been characterised. Repetitive mutation has been proved for at least 16 CpG sites. All nonsense mutations cause severe disease. Most missense mutations appear to cause instability of the protein, but some are associated with production of dysfunctional factor VIII molecules, thereby localising functionally critical regions of the cofactor. Variable phenotype has been observed in association with three of the latter class of genotype. This catalogue of gene lesions in Haemophilia A will be updated annually. PMID- 1923752 TI - An X-linked zinc finger gene mapping to Xq21.1-q21.3 closely related to ZFX and ZFY: possible origins from a common ancestral gene. AB - We describe a new zinc finger gene sequence (CMPX1 or HGM symbol ZNF6; isolated by cross-hybridization of ZFY to clones in a testis cDNA library) which possesses a zinc finger domain closely related to the transcriptional activator gene ZFX. The putative acidic activation domain is only 11.5% homologous with ZFX, whereas the putative DNA binding domain shares 75% homology and shows the same organisation composed of a basic two fingered repeat unit. ZNF6 has an unusually large 5' untranslated region (UTR) of 1.2 Kb which contains 26 potential ATG initiation codons, only one of which is associated with a long open reading frame. Southern and Northern blot analysis has shown that this 5' UTR is shared with many other sequences in the genome and transcribed associated with a large range of mRNA species. In situ hybridisation, analysis of somatic cell hybrids and male individuals carrying deleted X chromosomes have mapped the gene to Xq21.1-q21.3. The gene is highly conserved amongst the primates, in the mouse and can be detected weakly in the genome of a metatherian mammal (possum). Dosage in male and female mice indicates that it is also X-linked in this species. Possible origins of ZFX, ZFY and CMPX1 from a common ancestral gene are discussed. PMID- 1923753 TI - Complementation by detached parts of GGCC-specific DNA methyltransferases. AB - Individually inactive N- and C-terminal fragments of the m5C-methyltransferase M.BspRI can complement each other resulting in specific, in vivo methylation of the DNA. This was shown by cloning the coding regions for N- and C-terminal parts of the enzyme in compatible plasmids and co-transforming them into E.coli cells. The enzyme could be detached at several different sites, producing either non overlapping or partially overlapping fragments capable of complementation. Reconstitution of the active methyltransferase from inactive fragments was demonstrated in vitro, as well. Another GGCC-specific methyltransferase, M.BsuRI, showed a similar complementation phenomenon. Moreover, interspecies complementation was observed between appropriate fragments of the two closely related enzymes M.BspRI and M.BsuRI. Fragments of structurally and functionally more different methyltransferases were unable to complement each other. PMID- 1923754 TI - Cloning DPB3, the gene encoding the third subunit of DNA polymerase II of Saccharomyces cerevisiae. AB - DNA polymerase II purified from Saccharomyces cerevisiae contains polypeptides with apparent molecular masses of greater than 200, 80, 34, 30 and 29 kDa, the two largest of which (subunits A and B) are encoded by the essential genes POL2 and DPB2. By probing a lambda gt11 expression library of yeast DNA with antiserum against DNA polymerase II, we isolated a single gene, DPB3, that encodes both the 34- and 30-kDa polypeptides (subunit C and C'). The nucleotide sequence of DPB3 contained an open reading frame encoding a 23-kDa protein, significantly smaller than the observed molecular masses, 34- or 30-kDa, which might represent post translationally modified forms of the DPB3 product. The predicted amino acid sequence contained a possible NTP-binding motif and a glutamate-rich region. NTP binding motif and a glutamate-rich region. A dpb3 deletion mutant (dpb3 delta) was viable and yielded a DNA polymerase II lacking the 34- and 30-kDa polypeptides. dpb3 delta strains exhibited an increased spontaneous mutation rate, suggesting that the DPB3 product is required to maintain fidelity of chromosomal replication. Since a fifth, 29-kDa polypeptide was present in DNA polymerase II preparations from wild-type cell extracts throughout purification, the subunit composition appears to be A, B, C (or C and C') and D. The 5' nontranscribed region of DPB3 contained the MulI-related sequence ACGCGA, while the 0.9-kb DPB3 transcript accumulated periodically during the cell cycle and peaked at the G1/S boundary. The level of DPB3 transcript thus appears to be under the same cell cycle control as those of POL2, DPB2 and other DNA replication genes. DPB3 was mapped to chromosome II, 30 cM distal to his7. PMID- 1923756 TI - Proposed secondary structure of eukaryotic U14 snRNA. AB - U14 snRNA is a small nuclear RNA that plays a role in the processing of eukaryotic ribosomal RNA. We have investigated the folded structure of this snRNA species using comparative analysis of evolutionarily diverse U14 snRNA primary sequences coupled with nuclease digestion analysis of mouse U14 snRNA. Covariant nucleotide analysis of aligned mouse, rat, human, and yeast U14 snRNA primary sequences suggested a basic folding pattern in which the 5' and 3' termini of all U14 snRNAs were base-paired. Subsequent digestion of mouse U14 snRNA with mung bean (single-strand-specific), T2 (single-strand-preferential), and V1 (double strand-specific) nucleases defined the major and minor cleavage sites for each nuclease. This digestion data was then utilized in concert with the comparative sequence analysis of aligned U14 snRNA primary sequences to refine the secondary structure model suggested by computer-predicted folding. The proposed secondary structure of U14 snRNA is comprised of three major hairpin/helical regions which includes the helix of base-paired 5' and 3' termini. Strict and semiconservative covariation of specific base-pairs within two of the three major helices, as well as nucleotide changes that strengthen or extend base-paired regions, support this folded conformation as the evolutionary conserved secondary structure for U14 snRNA. PMID- 1923755 TI - The yeast putative transcriptional repressor RGM1 is a proline-rich zinc finger protein. AB - I have cloned a yeast gene, RGM1, which encodes a proline-rich zinc, finger protein. rgm1 mutants do not show any obvious phenotype but overexpression of RGM1 gene greatly impairs cell growth. The proline-rich region of RGM1 attached to a heterologous DNA binding domain is able to repress the expression of the target gene. RGM1 shares similar zinc finger motifs with the mammalian Egr (early growth response) proteins as well as proline-rich sequences with a high serine and threonine content, suggesting that RGM1 and Egr proteins could have functional similarities. PMID- 1923757 TI - The structure of a gene containing introns and encoding rat ribosomal protein P2. AB - The single rat ribosomal protein P2 gene containing introns has been characterized. It has 2275 nucleotides distributed in 5 exons and 4 introns. The sequence of amino acids encoded in the exons corresponds exactly to that derived before from a cDNA. Only this one P2 gene in a family of approximately 9 members has introns and is expressed. There are two transcriptional start sites (adjacent cytidine residues) located in a tract of 10 pyrimidines flanked by GC-rich regions. The P2 gene, like other mammalian ribosomal protein genes, lacks a TATA box; however, it has at positions -30 to -27 the sequence TTTA which may be a degenerate TATA box and may serve the same function. The architecture of the P2 gene, and especially the structure of the promoter region, resembles that of other mammalian ribosomal protein genes. This suggests that the common features contribute to the coordinate regulation of their transcription and that the stoichiometry of P2 (it is present in 2 copies in the ribosome) is achieved by regulation of the translation of its mRNA. PMID- 1923758 TI - DNA binding properties of YB-1 and dbpA: binding to double-stranded, single stranded, and abasic site containing DNAs. AB - A number of eukaryotic DNA binding proteins have been isolated by screening phage expression libraries with DNA probes containing the binding site of the DNA binding protein. This methodology was employed here to isolate clones of the factor that interacts with the W box element of the human major histocompatibility complex HLA-DQB gene. Surprisingly, several cDNA clones of YB 1, a cDNA clone that was previously isolated with a CCAAT element-containing sequence were found. Independently, the screening of phage expression libraries with depurinated DNA resulted in the isolation of YB-1 and dbpA, a previously isolated cDNA that has homology to YB-1. Additional characterization of YB-1 showed that it bound a wide variety of DNA sequences and suggested that the binding of this protein is promiscuous. Furthermore, we show that both YB-1 and dbpA bind to depurinated DNA better than undamaged DNA and that the extent of specificity of binding is influenced by Mg2+. Due to the lack of sequence specificity and high degree of binding to depurinated DNA, we suggest that these proteins might be involved in chromosome functions such as maintenance of chromatin structure or DNA repair that do not require sequence-specific binding. PMID- 1923759 TI - The Staphylococcus aureus chromosomal gene plaC, identified by mutations amplifying plasmid pT181, encodes a sigma factor. AB - The Staphylococcus aureus chromosomal gene plaC, identified by mutations such as plaC1 that lead to the amplification of plasmid pT181, has been cloned and sequenced. The plaC gene encodes a protein with high similarity (79% identity) with the vegetative sigma factor of Bacillus subtilis, sigA, suggesting that it acts as an RNA polymerase sigma factor in S.aureus. The plaC1 mutation was found to be a C to T transition leading to a proline to serine substitution at amino acid residue 209 of the protein. In other sigma factors this region of the protein is involved in specific recognition of the -10 promoter sequence. The change in sigma factor activity due to this mutation is characterized by its strict specificity for a limited number of promoters and the rather high amplitude of the effect. PMID- 1923760 TI - Regulatory regions of rat insulin I gene necessary for expression in transgenic mice. AB - Ten transgenic mouse lines harboring the -346/-103 fragment of the rat insulin I enhancer linked to a heterologous promoter and a reporter gene (Eins-Ptk-CAT construct) were produced. Expression of the hybrid transgene was essentially observed in pancreas and to a lesser extent in brain. These results indicate that the rat insulin I promoter is dispensable for pancreatic expression. This insulin gene sequence is the shortest fragment described as conferring tissue-specific expression in transgenic mice. Two short homologous sequences in the rat insulin I enhancer fragment used, IEB2 and IEB1, have been described as playing a dominant role in the regulation of HIT hamster insulinoma cell-specific transcription of the insulin gene (1). We investigated whether the combination of IEB2 and IEB1 sequences is sufficient to confer specific expression in transgenic mice to a IEB2-IEB1-Ptk-CAT gene construct. No CAT activity was observed neither in pancreas nor in any other organ examined in 19 different transgenic mice. Moreover in transient expression experiments in RIN2A rat insulinoma cells, the IEB sequences had a very weak or no enhancer activity. These observations contribute to the conclusion that DNA regulatory elements other than the IEB sequences are necessary for gene expression in vivo. PMID- 1923761 TI - Determination of the DNA-interacting region of the archaebacterial chromosomal protein MC1. Photocrosslinks with 5-bromouracil-substituted DNA. AB - Protein MC1 is the major chromosomal protein in methanosarcinaceae. Using photochemical crosslinking on 5-bromouracil-substituted DNA, we identified the region of the protein that interacts with it. This region is located in the C terminal part of the polypeptide chain, and the crosslinked amino-acids are in the region 74-86. Tryptophan 74 is one of the amino-acids crosslinked to DNA. PMID- 1923762 TI - Rescue of end fragments of yeast artificial chromosomes by homologous recombination in yeast. AB - Yeast artificial chromosomes (YACs) provide a powerful tool for the isolation and mapping of large regions of mammalian chromosomes. We developed a rapid and efficient method for the isolation of DNA fragments representing the extreme ends of YAC clones by the insertion of a rescue plasmid into the YAC vector by homologous recombination. Two rescue vectors were constructed containing a yeast LYS2 selectable gene, a bacterial origin of replication, an antibiotic resistance gene, a polylinker containing multiple restriction sites, and a fragment homologous to one arm of the pYAC4 vector. The 'end-cloning' procedure involves transformation of the rescue vector into yeast cells carrying a YAC clone, followed by preparation of yeast DNA and transformation into bacterial cells. The resulting plasmids carry end-specific DNA fragments up to 20 kb in length, which are suitable for use as hybridization probes, as templates for direct DNA sequencing, and as probes for mapping by fluorescence in situ hybridization. These vectors are suitable for the rescue of end-clones from any YAC constructed using a pYAC-derived vector. We demonstrate the utility of these plasmids by rescuing YAC-end fragments from a human YAC library. PMID- 1923763 TI - Multiwavelength fluorescence detection for DNA sequencing using capillary electrophoresis. AB - Multiwavelength detection of laser induced fluorescence for dideoxynucleotide DNA sequencing with four different fluorophores and separation by capillary gel electrophoresis is described. A cryogenically cooled, low readout noise, 2 dimensional charge-coupled device is used as a detector for the on-line, on column recording of emission spectra. The detection system has no moving parts and provides wavelength selectivity on a single detector device. The detection limit of fluorescently labeled oligonucleotides meets the high sensitivity requirements for capillary DNA sequencing largely due to the efficient operation of the CCD detector with a 94% duty cycle. Using the condition number as a selectivity criterion, multiwavelength detection provides better analytical selectivity than detection with four bandpass filters. Monte Carlo studies and analytical estimates show that base assignment errors are reduced with peak identification based on entire emission spectra. High-speed separation of sequencing samples and the treatment of the 2-dimensional electropherogram data is presented. Comparing the DNA sequence of a sample separated by slab gel electrophoresis with sequence from capillary gel electrophoresis and multiwavelength detection we find no significant difference in the amount of error attributable to the instrumentation. PMID- 1923764 TI - Effects of an abasic site on triple helix formation characterized by affinity cleaving. AB - The stability of triple helical complexes of pyrimidine oligodeoxyribonucleotides containing one abasic 1,2-dideoxy-D-ribose (phi) residue was examined by affinity cleaving. Within a pyrimidine third strand, the triplets phi.AT, phi.GC, phi.TA and phi.CG are significantly less stable than the triplets, T.AT, C+GC and G.TA. The decrease in binding produced by an abasic residue is similar to that observed with imperfectly matched natural base triplets, with phi.AT and phi.GC being less stable than phi.TA and phi.CG triplets for the sequences studied. PMID- 1923765 TI - Fidelity of DNA synthesis by the Thermococcus litoralis DNA polymerase--an extremely heat stable enzyme with proofreading activity. AB - We demonstrate that the DNA polymerase isolated from Thermococcus litoralis (VentTM DNA polymerase) is the first thermostable DNA polymerase reported having a 3'----5' proofreading exonuclease activity. This facilitates a highly accurate DNA synthesis in vitro by the polymerase. Mutational frequencies observed in the base substitution fidelity assays were in the range of 30 x 10(-6). These values were 5-10 times lower compared to other thermostable DNA polymerases lacking the proofreading activity. All classes of DNA polymerase errors (transitions, transversions, frameshift mutations) were assayed using the forward mutational assay (1). The mutation frequencies of Thermococcus litoralis DNA polymerase varied between 15-35 x 10(-4) being 2-4 times lower than the respective values obtained using enzymes without proofreading activity. We also noticed that the fidelity of the DNA polymerase from Thermococcus litoralis responds to changes in dNTP concentration, units of enzyme used per one reaction and the concentration of MgSO4 relative to the total concentration of dNTPs present in the reaction. The high fidelity DNA synthesis in vitro by Thermococcus litoralis DNA polymerase provides good possibilities for maintaining the genetic information of original target DNA sequences intact in the DNA amplification applications. PMID- 1923766 TI - Complex pattern of alternative splicing generates unusual diversity in the leader sequence of the chicken link protein mRNA. AB - We report here the isolation of the 5' end and the promoter region of the gene for chicken cartilage link protein, and demonstrate extensive heterogeneity of the leader sequence arising from differential utilization of multiple splice sites within the 5'-most exon. The 500-base pairs (bp) exon 1 consists of solely untranslated sequence and is followed by an intron greater than 33 kilobase pairs (kb). Together, the five exons predict a gene size longer than 100 kb. Multiple transcription initiation sites were mapped 34, 46, 56, 66 and 76 bp downstream of a TATA-like motif. Sequence analysis revealed that in addition to the non-spliced variant, multiple mRNA species were generated by alternative splicing resulting in the exclusion of 92, 166, 170, 174 and 263 nucleotides (nt), respectively, from exon 1. Polymerase chain reaction confirmed the existence of various splice forms, and showed cell type- and developmental stage-specific expression for one group of them. Secondary structure predictions indicated that the leaders of the splice forms could form stable hairpin structures with different free energies of formation (up to delta G = -110 kcal/mol), suggesting translational control. The splice variant detected in the largest amount had the least stable predicted hairpin (delta G = -31.7 kcal/mol). PMID- 1923767 TI - Structure and expression during development of Drosophila melanogaster gene for DNA polymerase alpha. AB - The Drosophila melanogaster gene and cDNA which span the entire open reading frame for DNA polymerase alpha, were cloned, and their nucleotide sequences were determined. The gene consists of 6 exons separated by 5 short introns. The major transcription initiation site was localized 85 bp upstream from the initiation codon. The nucleotide sequence of the open reading frame revealed a polypeptide of 1,505 amino acid residues with a molecular weight of 170,796. The amino acid sequence of the polypeptide was 37% homologous with that of the catalytic subunit of human DNA polymerase alpha. This sequence contains six regions, the orders and amino acid sequences of which are highly conserved among a number of other viral and eukaryotic DNA polymerases. We found 7 amino acid residues in the region between the 639th and 758th positions, identical to those essential for the active site of Escherichia coli DNA polymerase I-associated 3'----5' exonuclease. Thus, the exonuclease activity may be associated with Drosophila DNA polymerase alpha. Levels of the DNA polymerase alpha mRNA were high in unfertilized eggs and early embryos, relatively high in adult female flies and second-instar larva, and low in bodies at other stages of development. This feature of the expression is similar to that of the proliferating cell nuclear antigen (an auxiliary protein of DNA polymerase delta) and seems to coincide with the proportions of proliferating cells in various developmental stages. As the half life of the mRNA for DNA polymerase alpha in cultured Drosophila Kc cells was 15 min, expression of the DNA polymerase alpha gene is probably strictly regulated at the step of transcription. PMID- 1923768 TI - DNase I hypersensitive sites flank the mouse class II major histocompatibility complex during B cell development. AB - The mouse class II major histocompatibility complex (MHC) encodes a polymorphic, multigene family important in the immune response, and is expressed mainly on mature B cells, on certain types of dendritic cells and is also inducible by gamma-interferon on antigen presenting cells. To study the regulatory elements which control this expression pattern, we have examined the chromatin structure flanking the class II MHC region, in particular during B cell differentiation. Using a panel of well-characterised mouse cell lines specific for different stages of B cell development (pre-B, B, plasma cell) as well as non-B cell lines, we have mapped the DNase I hypersensitive (DHS) sites adjacent to the mouse MHC class II region. The results presented show, for the first time that there are specific hypersensitive sites flanking the class II MHC locus during pre B cell, B cell and plasma cell stages of B cell differentiation, irrespective of the status of class II MHC expression. These hypersensitive sites are not found in T cell, fibroblast or uninduced myelomonocytic cell lines. This suggests that these DHS sites define a developmentally stable, chromatin structure, which can be used as a marker of B cell lineage commitment and may indicate that a combination of these hypersensitive sites reflect regulatory proteins involved in the immediate expression of a particular class II MHC gene or possibly control of the entire locus. PMID- 1923769 TI - Sequence and functional characterization of the human purine nucleoside phosphorylase promoter. AB - Purine nucleoside phosphorylase (PNP) is a ubiquitously expressed enzyme which contributes to the catabolism and recycling of nucleotides. To characterize the promoter region of the human PNP gene, the nucleotide sequence from a BamHI site located in the 5' untranslated region extending 2237 bp upstream to an XbaI site was determined. The transcriptional start site as determined by primer extension was 119 bp upstream of the coding sequence and consisted of a 5'-CA-3' dimer with A at +1. A TATA box was identified -24 to -29 bp upstream of the transcriptional start site. A CCAAT pentamer sequence in the inverted orientation was present at 51 to -55 bp and two GC rich regions were identified at -68 to -81 bp and -168 to -187 bp. Progressive 5' deletions of the 5' flanking region were fused to the chloramphenicol acetyltransferase (CAT) reporter gene and transient expression measured after transfection of murine NIH/3T3 fibroblasts. A 91 bp promoter (the shortest tested) provided CAT activity at 60% the level of a 216 bp promoter, possibly due to removal of the GC rich region between -168 and -187 bp. Longer promoters resulted in CAT expression at similar or lower levels than the 216 bp promoter indicating that this region contained all of the 5' flanking sequences affecting transcription from the PNP promoter. PMID- 1923770 TI - Functional analysis of the tobacco mosaic virus tRNA-like structure in cytoplasmic gene regulation. AB - The 3'-untranslated region (UTR) of tobacco mosaic virus (TMV), which terminates in a tRNA-like structure, functionally substitutes for a poly(A) tail in both plant and animal cells. The addition of the TMV 3'-UTR to chimeric mRNA constructs increases their expression up to 100-fold, increasing both translational efficiency and mRNA stability. The domain largely responsible for the regulation maps to a 72 base region immediately upstream of the tRNA-like structure, however, the 3'-terminal, tRNA-like structure is required for full function. Its contribution is lost if separated from the upstream pseudoknot domain by as few as 5 bases or if 6 bases are removed from the 3'-terminus. Sequence addition to the 3'-terminus of the TMV 3'UTR or the upstream pseudoknot domain inhibits function in both tobacco and Chinese hamster ovary cells. PMID- 1923771 TI - In vitro and in vivo analysis of the c-myc RNA polymerase III promoter. AB - The c-myc promoter has the unusual property of displaying both RNA polymerase II (Pol II) and RNA polymerase III (Pol III) activities. Both Pol II and Pol III utilize the same transcription initiation site. We have now examined the effects of mutations in crucial regions of the c-myc promoter to assess their effects on both transcriptional activities. In doing this we show that both Pol II and Pol III activities require sequences that are located within the stronger of the two principal c-myc promoter regions (P2). Further, we show that the Pol III activity using this initiation site does not require an A box or distal upstream sequences. Like the Pol II activity, it does require an intact TATA sequence and alterations at this site result in the simultaneous loss of both Pol II and Pol III activities. The superimposition of two apparently inseparable promoter activities makes it possible to consider common features, possible common protein elements in each holoenzyme complex, as well as a potential role for each enzyme in the regulated expression of the c-myc gene. PMID- 1923773 TI - The nucleotide sequence of the 5S ribosomal RNA gene of Pyrenophora graminea. PMID- 1923772 TI - A temperature sensitive mutant of Saccharomyces cerevisiae defective in pre-rRNA processing. AB - A recessive temperature sensitive mutant has been isolated that is defective in ribosomal RNA processing. By Northern analysis, this mutant was found to accumulate three novel rRNA species: 23S', 18S' and 7S', each of which contains sequences from the spacer region between 25S and 18S rRNA. 35S pre-rRNA accumulates, while the level of the 20S and 27S rRNA processing intermediates is depressed. Pulse-chase analysis demonstrates that the processing of 35S pre-rRNA is slowed. The defect in the mutant appears to be at the first processing step, which generates 20S and 27S rRNA. 7S' RNA is a form of 5.8S RNA whose 5' end is extended by 149 nucleotides to a position just 5 nucleotides downstream of the normal cleavage site that produces 20S and 27S rRNA. 7S' RNA can assemble into 60S ribosomal subunits, but such subunits are relatively ineffective in joining polyribosomes. A single lesion is responsible for the pre-rRNA processing defect and the temperature sensitivity. The affected gene is designated RRP2. PMID- 1923774 TI - trnR-CCG is not unique to the plastid DNA of the liverwort Marchantia: gene identification from the moss Physcomitrella patens. PMID- 1923775 TI - Nucleotide sequence of PUP1 encoding a putative proteasome subunit in Saccharomyces cerevisiae. PMID- 1923776 TI - Esp3I--a novel type IIs restriction endonuclease from Hafnia alvei that recognizes the sequence 5'-CGTCTC(N)1/5-3'. PMID- 1923777 TI - Molecular cloning and nucleotide sequences of cDNAs for histone H1 and H2B variants from wheat. PMID- 1923779 TI - Excessive cycling converts PCR products to random-length higher molecular weight fragments. PMID- 1923778 TI - Sequence analysis of hepatitis B virus genome of a new mutant of ayw subtype isolated in Sardinia. PMID- 1923780 TI - Enhanced evolutionary PCR using oligonucleotides with inosine at the 3'-terminus. PMID- 1923781 TI - Vermilion as a small selectable marker gene for Drosophila transformation. PMID- 1923782 TI - Microisolation of yeast nucleic acids on the microtitre plate without using lytic enzymes. PMID- 1923783 TI - An STS in the human adenosine deaminase gene (located 20q12-q13.11). PMID- 1923784 TI - An STS in the human cytoskeletal gamma-actin gene. PMID- 1923785 TI - An STS in the human skeletal alpha-actin gene. PMID- 1923786 TI - Dinucleotide repeat polymorphisms at the DXS294 and DXS300 loci in Xq26. PMID- 1923787 TI - VNTR polymorphism in the hepatic lipase gene (LIPC). PMID- 1923788 TI - A CCA/CCG neutral dimorphism in the codon for Pro 626 of the human protein S gene PS alpha (PROS1). PMID- 1923789 TI - Dinucleotide repeat polymorphism at the D17S518 locus. PMID- 1923790 TI - Dinucleotide repeat polymorphism at the D8S161 locus. PMID- 1923791 TI - Dinucleotide repeat polymorphism at the RYR1 locus (19q13.1). PMID- 1923792 TI - Microsatellite polymorphism in human insulin receptor gene (INSR) on chromosome 19. PMID- 1923793 TI - Microsatellite polymorphism at the D9S12 locus. PMID- 1923794 TI - MicroVNTR (CTTT)n at the apo C-III locus. PMID- 1923795 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1923796 TI - Identification and expression of the cDNA of KIN17, a zinc-finger gene located on mouse chromosome 2, encoding a new DNA-binding protein. AB - We report the cloning of KIN17 cDNA, 1414 bp long with an ORF of 391 residues showing a zinc finger and nuclear localization signals. By recloning the cDNA into an appropriate vector, we produced kin17 protein in E. coli, purified it partially and shown that kin17 protein binds to double-stranded DNA. The KIN17 gene was localized by cytogenetic mapping in mouse chromosome 2, band A. Genomic sequences homologous to KIN17 cDNA were detected also in rat and human DNAs. KIN17 mRNA is highly expressed in rodent transformed AtT-20 neuroendocrine cells whereas it can be detected only in the total RNA of mouse embryos and various normal adult tissues by reverse transcription and PCR amplification. The mouse nuclear kin17 protein was identified by a local small structural similarity with E.coli recA protein. Kin17 and recA have only 39 amino acid residues in a region that might be involved in DNA-binding. PMID- 1923797 TI - Construction of a novel RNA-transcript-trimming plasmid which can be used both in vitro in place of run-off and (G)-free transcriptions and in vivo as multi sequences transcription vectors. AB - We have constructed a new transcription system that allows trimming of both 5' and 3'-termini of any RNA transcripts by means of cis-acting ribozyme activities. The vector consists of a promoter, '5' Processing Ribozyme', any DNA template to be transcribed, and '3' Processing Ribozyme' sequences. When the vector possessing T7 promoter was tested in vitro, the transcription efficiency from the circular template was over ten-fold higher than using linearized template (run off transcription). Further, since uniform RNAs with defined 5'- and 3'-ends can be produced, this strategy complements the conventional run-off transcription. Also the 5'-/3'-trimmed uniform RNA can function as a reporter in elucidating transcription factors and promoter regions in vitro, this strategy can replace the widely used (G)-free transcription (Sawadogo and Roeder (1985) Proc. Natl. Acad. Sci. USA 82, 4394-4398). With this strategy, in addition to the advantage that the template DNA need not be linearized prior to transcription, a cytidine minus sequence is no longer necessary for quantitative analysis of transcription factors. Since any sequences including those of RNA virus can be inserted between the '5' Processing Ribozyme' and the '3' Processing Ribozyme' sequences, and the entire unit can be inserted into any genes under active transcription, this construct is useful like that of Dzianott and Bujarski ((1989) Proc. Natl. Acad. Sci. USA 86, 4823-4827) for RNA virologists because these strategies provide RNA transcripts without heterologous sequences which may greatly diminish infectivity. Moreover, since the construct can also be used in vivo, multi transcripts such as trans-acting ribozymes targeted to various sites would be produced by concatenating the entire units in tandem. PMID- 1923798 TI - Cell cycle regulation and in vitro hybrid arrest analysis of the major human uracil-DNA glycosylase. AB - Uracil-DNA glycosylase (UDG) is the first enzyme in the excision repair pathway for removal of uracil in DNA. In vitro transcription/translation of a cloned human cDNA encoding UDG resulted in easily measurable UDG activity. The apparent size of the primary translation product was 34 kD. Two lines of evidence indicated that this cDNA encodes the major nuclear UDG. First, in vitro translation of human fibroblast mRNA isolated from S-phase cells resulted in measurable UDG activity and this UDG translation was specifically inhibited 90% by an anti-sense UDG mRNA transcript. Secondly, cell cycle analysis revealed an 8 12 fold increase in transcript level late in the G1-phase preceding a 2-3 fold increase in total UDG activity in the S-phase. UDG degradation was found to be very slow (T1/2 approximately 30h), therefore, the rate of UDG synthesis could be derived from the rate of UDG accumulation, and was found to correlate temporarily and quantitatively with the transcript level. Inhibitor studies showed that RNA and protein synthesis was required for induction of UDG. However, specific inhibition of DNA replication with aphidicolin indicated that entrance of fibroblasts into the S-phase was not required for UDG accumulation. PMID- 1923799 TI - Activation of restriction endonuclease EcoRII does not depend on the cleavage of stimulator DNA. AB - The restriction endonuclease EcoRII is unable to cleave DNA molecules when recognition sites are very far apart. The enzyme, however can be activated in the presence of DNA molecules with a high frequency of EcoRII sites or by oligonucleotides containing recognition sites: Addition of the activator molecules stimulates cleavage of the refractory substrate. We now show that endonucleolysis of the stimulator molecules is not a necessary prerequisite of enzyme activation. A total EcoRII digest of pBR322 DNA or oligonucleotide duplexes with simulated EcoRII ends (containing the 5' phosphate group), as well as oligonucleotide duplexes containing modified bases within the EcoRII site, making them resistant to cleavage, are all capable of enzyme activation. For activation EcoRII requires the interaction with at least two recognition sites. The two sites may be on the same DNA molecule, on different oligonucleotide duplexes, or on one DNA molecule and one oligonucleotide duplex. The efficiency of functional intramolecular cooperation decreases with increasing distance between the sites. Intermolecular site interaction is inversely related to the size of the stimulator oligonucleotide duplex. The data are in agreement with a model whereby EcoRII simultaneously interacts with two recognition sites in the active complex, but cleavage of the site serving as an allosteric activator is not necessary. PMID- 1923800 TI - The use of oligodeoxynucleotide probes in chaotrope-based hybridization solutions. AB - Hybridization solutions containing chaotropes may be used to modulate the thermal stability (Tm or Td) of oligodeoxynucleotide (ODN) duplexes or hybrids over a 90 degrees C range. Modulation of Td allows formulation of hybridization solutions that permit ambient temperature hybridization using most combinations of probe length, probe composition, target type, and facilitates development of convenient and rapid assay formats. The conditions required to achieve ODN duplex fidelity, and optimal yields of hybridized product, are described for trichloroacetate, thiocyanate, guanidinium salts and other chaotropic salts. The effects of different solid supports on Td are described. Also, a method is presented that uses chaotropic compounds to reduce background arising from signal ODN probes in a sandwich assay hybridization format. PMID- 1923801 TI - Alpha-amanitin-resistant transcription units in trypanosomes: a comparison of promoter sequences for a VSG gene expression site and for the ribosomal RNA genes. AB - Transcription of the predominant surface antigen genes in Trypanosoma brucei is unusual in its resistance to the RNA polymerase inhibitor alpha-amanitin, a property typical for rDNA transcription in eukaryotes. Transcription of most other protein-coding genes in trypanosomes is sensitive to alpha-amanitin. To investigate whether RNA polymerase I, the polymerase that transcribes rRNA genes, can give rise to functional mRNAs in trypanosomes, we have fused the putative promoter of the T.brucei rRNA genes to the chloramphenicol acetyl transferase (CAT) gene and determined CAT activity after transient expression of chimeric constructs in procyclic trypanosomes. We show here that the rRNA promoter yields the same high CAT activity as the promoters for the two predominant surface antigen genes of trypanosomes, the Variant-specific Surface Glycoprotein (VSG) gene of bloodstream trypanosomes and the procyclin gene of insect-form trypanosomes, both of which are also transcribed by an alpha-amanitin-insensitive RNA polymerase. RNA polymerase I of trypanosomes seems therefore able to synthesize pre-mRNAs that are effectively processed into translatable mRNAs. Dissection of the promoter segments showed the minimal elements for a VSG gene expression site promoter to be confined to a segment of -60 to +77 bp, overlapping the most 5' putative transcription start sites as determined in vivo by RNase protection experiments. For the ribosomal promoter region a segment of 258 to +200 bp relative to the putative transcription start site was sufficient for maximal CAT activity. There is a precise requirement for specific nucleotides at the rRNA transcription start site. We detect no homology between the sequences required for promoter function of the three alpha-amanitin-resistant transcription units, rRNA, VSG and procyclin (parp) genes. This suggests that the sequence-specific recognition of these promoters either occurs by common factors detecting sequence homologies that escape us, or by separate factors that bind to different DNA sequences but interact with a common alpha-amanitin-resistant RNA polymerase. PMID- 1923802 TI - The solution structure of a DNA hairpin containing a loop of three thymidines determined by nuclear magnetic resonance and molecular mechanics. AB - We have determined by two-dimensional nuclear magnetic resonance studies and molecular mechanics calculations the three-dimensional solution structure of a 21 residue oligonucleotide capable of forming a hairpin structure with a loop of three thymidine residues. This structure is in equilibrium with a duplex form. At 33 degrees C, low ionic strength and in the presence of MgCl2 the hairpin form dominates in solution. Six Watson-Crick base pairs are formed topped by the loop structure. The residues 1-3 and 18-21 are not complementary and form dangling ends. Distance constraints have been derived from nuclear Overhauser enhancement measurements. These, together with molecular mechanics calculations, have been used to determine the structure. We do not observe stacking of thymidine residues either over the 3' or the 5' end of the stem. PMID- 1923803 TI - Initiation of translation at an AUA codon for an archaebacterial protein gene expressed in E.coli. AB - Overexpression of the Sulfolobus solfataricus L12 ribosomal protein gene in E.coli cells yielded two products of different size. If the E.coli cells carrying the overexpression plasmid were induced in the early stage of bacterial growth, the smaller of the two products was almost exclusively produced. However, induction in a late stage of bacterial growth yielded the larger product in significant excess. The larger protein was identified as the translation product of the entire SsoL12 gene, while the smaller product was a N-terminally shortened version of the L12 protein (sh-SsoL12), starting with a N-terminal methionine at position 22 of the coded protein and continuing with the predicted protein sequence. Position 22 is an isoleucine in the complete SsoL12 protein sequence, coded by an AUA codon. A subclone (SsoL12**) of the SsoL12 gene containing overexpression plasmid, lacking the regular AUG start codon and the putative Shine Dalgarno sequence, was constructed to determine if E.coli ribosomes could initiate at this AUA codon. During overexpression the SsoL12** construct yielded exclusively the sh-SsoL12 product in significant amounts. An AUA start codon has never been found before in a natural message. However, experiments utilizing site directed mutagenesis to generate AUA start codons showed that this codon can be functional for initiation in prokaryotes and eukaryotes. The findings presented in this paper show that AUA acts as an initiation codon in a natural message expressed in a heterologous organism. PMID- 1923805 TI - Intercalation of psoralen into DNA of plastid chromosomes decreases late during barley chloroplast development. AB - We have used a DNA crosslinking assay to measure intercalation of the psoralen derivative HMT (4'-hydroxymethyl-4,5',8-trimethylpsoralen) into barley (Hordeum vulgare) plastid chromosomal DNA during chloroplast and etioplast development. Intercalation into DNA in intact plastids in vivo and in plastid lysates in vitro shows that chromosomal DNA in the most mature chloroplasts intercalates HMT less efficiently than DNA in younger chloroplasts. In contrast, there is no change in HMT intercalation during etioplast differentiation in the dark. Our results also show that DNA in higher plant plastid chromosomes is under superhelical tension in vivo. The lower susceptibility to HMT intercalation of DNA in the most mature chloroplasts indicates that late during chloroplast development the superhelical tension or the binding of proteins to the DNA or both change. PMID- 1923806 TI - Oligodeoxyribonucleotide ligation to single-stranded cDNAs: a new tool for cloning 5' ends of mRNAs and for constructing cDNA libraries by in vitro amplification. AB - Cloning full length cDNAs is a difficult task especially if mRNAs are not abundant or if tissue is only available in limited amounts. Current strategies are based on in vitro amplification of cDNAs after adding a homopolymeric tail at the 3' end of the ss-cDNA. Since subsequent amplification steps yield unspecific amplified DNA mostly due to non-specific annealing of the reverse primer containing a homopolymeric tail, we have devised a new strategy based on the ligation of single-stranded oligodeoxyribonucleotide to the 3' end of single stranded cDNAs. The efficiency of the strategy was assessed by analyzing the 5' ends of the rat pineal gland tryptophan hydroxylase messenger. The 5' end of the least abundant messenger (0.005% of total mRNAs) could be cloned without selection. Sixty percent of the analyzed clones correspond to TPH. This technique revealed a 5-nt stretch not apparent using dG tailing strategy. The potentiality of the method for generating cDNAs libraries was tested with 10(4) PC12 cells. In this library, the abundance of tyrosine hydroxylase clones (0.03%) correlated well with the abundance of the corresponding messenger, showing that no major distortion was introduced into the construction of the library. PMID- 1923804 TI - A DNA binding domain is contained in the C-terminus of wild type p53 protein. AB - In the present study we evaluated the DNA binding activity of wild type and mutant p53 proteins that were isolated from bacterial expression vectors. A comparison of the binding activities of the various purified p53 proteins, assessed by their ability to bind DNA cellulose columns, indicated that wild type p53 has a higher affinity to DNA than have mutant p53 forms. Furthermore, only wild type p53 was able to bind genomic DNA upon electrophoretic protein blotting. As specific deletion of the C-terminal region of wild type p53 totally abolished binding to genomic DNA, it was concluded that the 47 C-terminal amino acids contain the DNA binding region. The fact that the N-terminus contains a transcription activation region whereas the C-terminus contains a DNA binding domain places p53 in the family of typical transcription factors. Our experiments show that the topographical positioning of these domains plays an important role in the activity of wild type p53. PMID- 1923807 TI - Orientation of the Lac repressor DNA binding domain in complex with the left lac operator half site characterized by affinity cleaving. AB - Lac repressor (LacR) is a helix-turn-helix motif sequence-specific DNA binding protein. Based on proton NMR spectroscopic investigations, Kaptein and co-workers have proposed that the helix-turn-helix motif of LacR binds to DNA in an orientation opposite to that of the helix-turn-helix motifs of lambda repressor, lambda cro, 434 repressor, 434 cro, and CAP [Boelens, R., Scheek, R., van Boom, J. and Kaptein, R., J. Mol. Biol. 193, 1987, 213-216]. In the present work, we have determined the orientation of the helix-turn-helix motif of LacR in the LacR DNA complex by the affinity cleaving method. The DNA cleaving moiety EDTA.Fe was attached to the N-terminus of a 56-residue synthetic protein corresponding to the DNA binding domain of LacR. We have formed the complex between the modified protein and the left DNA half site for LacR. The locations of the resulting DNA cleavage positions relative to the left DNA half site provide strong support for the proposal of Kaptein and co-workers. PMID- 1923808 TI - Species-specific patterns of DNA bending and sequence. AB - Nucleotide sequences in the GenEMBL database were analyzed using strategies designed to reveal species-specific patterns of DNA bending and DNA sequence. The results uncovered striking species-dependent patterns of bending with more variations among individual organisms than between prokaryotes and eukaryotes. The frequency of bent sites in sequences from different bacteria was related to genomic A + T content and this relationship was confirmed by electrophoretic analysis of genomic DNA. However, base composition was not an accurate predictor for DNA bending in eukaryotes. Sequences from C. elegans exhibited the highest frequency of bent sites in the database and the RNA polymerase II locus from the nematode was the most bent gene in GenEMBL. Bent DNA extended throughout most introns and gene flanking segments from C.elegans while exon regions lacked A tract bending characteristics. Independent evidence for the strong bending character of this genome was provided by electrophoretic studies which revealed that a large number of the fragments from C.elegans DNA exhibited anomalous gel mobilities when compared to genomic fragments from over 20 other organisms. The prevalence of bent sites in this genome enabled us to detect selectively C.elegans sequences in a computer search of the database using as probes C.elegans introns, bending elements, and a 20 nucleotide consensus sequence for bent DNA. This approach was also used to provide additional examples of species specific sequence patterns in eukaryotes where it was shown that (A) greater than or equal to 10 and (A.T) greater than or equal to 5 tracts are prevalent throughout the untranslated DNA of D.discodium and P.falciparum, respectively. These results provide new insight into the organization of eukaryotic DNA because they show that species-specific patterns of simple sequences are found in introns and in other untranslated regions of the genome. PMID- 1923809 TI - NMR studies for identification of dI:dG mismatch base-pairing structure in DNA. AB - One- and two-dimensional NMR experiments have been undertaken to investigate deoxyinosine:deoxyguanosine (dI:dG) base pairing in a self-complementary dodecadeoxyribonucleotide, d(C1-G2-C3-I4-A5-A6-T7-T8-G9-G10-G11-G12) (designated IG-12), duplex. The NMR data indicate formation of a dI(syn):dG(anti) base pair in a B-DNA helix. This unusual base pairing results in altered NOE patterns between the base protons (H8 and H2) of the I4 residue and the sugar protons of its own and the 5'-flanking C3 residues. The dI(syn):dG(anti) base pair is accommodated in the B-DNA duplex with only a subtle distortion of the local conformation. Identification of the dI:dG base pairing in this study confirms that a hypoxanthine base can form hydrogen-bonded base pairs with all of the four normal bases, C, A, T, and G, in DNA. PMID- 1923810 TI - A rat brain mRNA encoding a transcriptional activator homologous to the DNA binding domain of retroviral integrases. AB - We have isolated a rat cDNA, named FE65, hybridizing to an mRNA of about 2,300 nucleotides present in rat brain, undetectable in rat liver and very poorly represented in other tissues. An mRNA of the same size is present in human neuroblastoma cells and is absent from other human cell lines. The FE65 cDNA contains an open reading frame (ORF) coding for a polypeptide of 499 amino acids in which 143 residues can be aligned with the DNA binding domain of the integrases encoded by mammalian immunodeficiency viruses. The remaining part of the FE65 ORF is not homologous with the correspondent regions of the integrases; the first 206 residues of the FE65 ORF show numerous negative charges and a short sequence not dispensable for the function of the transactivating acidic domain of the jun family transcriptional factors. A plasmid which expresses FE65 amino acids 1-232 fused to the yeast GAL4 DNA binding domain was co-transfected with a plasmid containing five GAL4 binding sites upstream of a minimal Adenovirus promoter controlling the expression of the CAT gene. This experiment showed that the fused protein GAL4-FE65 is able to obtain a 30-40 fold increase of the CAT gene expression compared to the expression observed in the presence of the GAL4 DNA binding domain alone. Two types of FE65 mRNA are present in rat brain, differing only for six nucleotides. We demonstrate that this is the consequence of a neuron-specific alternative splicing of a six-nucleotide miniexon, which is also present in the human genome, in an intron/exon context very similar to that of the rat FE65 gene. PMID- 1923811 TI - Genomic fingerprinting using arbitrarily primed PCR and a matrix of pairwise combinations of primers. AB - Polymorphisms in genomic fingerprints generated by arbitrarily primed PCR (AP PCR) can distinguish between slightly divergent strains of any organism. Single oligodeoxyribonucleotide (oligo) primers have been used to generate such fingerprints, with the same primer being present at the 5' end of both strands for every PCR product. We used three arbitrary oligos, individually and in pairs, to generate six different genomic fingerprints of the same mouse genomic DNAs. Fewer than half of the products in genomic fingerprints generated using the oligos in pairs were the same as those produced by AP-PCR using one of the three oligos alone. Thus, a few oligos could be used in a very large number of single and pairwise combinations, each producing a distinct AP-PCR fingerprint with the potential to identify new polymorphisms. For example, 50 oligos can be used in a matrix of pairwise combinations to produce 2,500 fingerprints, in which at least half the data can be expected to be unique to each pair. We demonstrate this principle by using two oligos, alone and together, to generate three sets of fingerprints and map thirteen polymorphisms in the C57BL/6J x DBA/2J set of recombinant inbred mice. PMID- 1923812 TI - Ribosomes containing the C1054-deletion mutation in E. coli 16S rRNA act as suppressors at all three nonsense codons. AB - It was established some time ago that the deletion of base C1054 in E. coli 16S rRNA specifically affects UGA-dependent termination of translation. Based on this observation, a model for the termination event was proposed in which the UGA nonsense codon on the mRNA base-pairs with a complementary motif in 'helix 34' of the 16S rRNA, thus potentially providing a recognition signal for the binding of the release factor. This model has been re-examined here and evidence is presented which demonstrates that ribosomes containing the C1054 delta mutation enhance the activity of suppressors of both UAG and UAA termination codons introduced into the host. The results do not support the nonsense codon-16S rRNA base pairing model, and rather imply a more general involvement of 'helix 34' in the translation termination reactions. PMID- 1923813 TI - A chemical interference study on the interaction of ribosomal protein L11 from Escherichia coli with RNA molecules containing its binding site from 23S rRNA. AB - The interaction between ribosomal protein L11 from Escherichia coli and in vitro synthesized RNA containing its binding site from 23S rRNA was characterized by identifying nucleotides that interfered with complex formation when chemically modified by diethylpyrocarbonate or hydrazine. Chemically modified RNA was incubated with L11 under conditions appropriate for specific binding of L11 and the resulting protein-RNA complex was separated from unbound RNA on Mg(2+) containing polyacrylamide gels. The ability to isolate L11 complexes on such gels was affected by the extent of modification by either reagent. Protein-bound and free RNAs were recovered and treated with aniline to identify their content of modified bases. Exclusion of RNA containing chemically altered bases from L11 associated material occurred for 29 modified nucleotides, located throughout the region corresponding to residues 1055-1105 in 23S rRNA. Ten bases within this region did not reproducibly inhibit binding when modified. Multiple bands of RNA were consistently observed on the nondenaturing gels, suggesting that significant intermolecular RNA-RNA interactions had occurred. PMID- 1923814 TI - The influence of an alternate template conformation on elongating phage T7 RNA polymerase. AB - We investigated the effect of left-handed Z-DNA on transcription by bacteriophage T7 RNA polymerase in vitro and, surprisingly, found that the enzyme can efficiently utilize a template containing a stretch of left-handed DNA close to the promoter. Analysis of transcription products revealed that only a small fraction of elongating polymerases abort transcription either at the promoter proximal or at the distal B-to-Z junction and, even less frequently, within the stretch of left-handed DNA. Our results indicate that, unlike E. coli RNA polymerase, T7 RNA polymerase can utilize a template with a CG stretch in an alternate conformation. In contrast, polymerases are completely blocked at the promoter proximal junction by a monoclonal antibody directed against Z-DNA. This blockage remains stable over a remarkable time, even when negative supercoiling is released by linearization of the template. Together with our recent finding of transcription-induced formation of Z-DNA (3), our data provide an example for a possible auto-regulatory mechanism that employs a change in DNA conformation. PMID- 1923815 TI - Binding of human glutaminyl-tRNA synthetase to a specific site of its mRNA. AB - The human glutaminyl-tRNA synthetase is able to bind to its own mRNA. The enzyme contains two binding regions. One is located in the central section of the enzyme which includes its most hydrophilic portion with ten lysine residues in a block of 20 amino acids. This part of the enzyme binds unspecifically to all RNA sequences tested. A second binding region is located in that part of the enzyme which shows high degrees of sequence similarities with the bacterial and yeast glutaminyl-tRNA synthetases, and which is most likely responsible for the charging of tRNA with glutamine. This second RNA binding region specifically interacts with a site in the 3' noncoding region of the synthetase's mRNA. The binding site in the mRNA is characterized by an extended secondary structure that includes elements of the 'identity set' of nucleotides recognized by the enzyme when interacting with tRNA. We discuss possible physiological implications of the interaction between glutaminyl-tRNA synthetase and its mRNA. PMID- 1923816 TI - Dual modes of transcriptional and translational initiation of SSP1, the gene for a mitochondrial HSP70, responding to heat-shock in Schizosaccharomyces pombe. AB - The SSP1 gene of Schizosaccharomyces pombe which is homologous to the SSC1 gene of Saccharomyces cerevisiae was cloned and its nucleotide sequence determined. A heat-shock element and three possible TATA boxes were found upstream of the coding region. Dual modes of transcriptional initiation were observed in primer extension analyses using as templates the mRNAs prepared from cells before and after heat-shock. Initiation sites situated 50 to 60 nucleotides downstream of the normal one were found to be additionally used in cells after heat-shock. Thus, the mode of transcription in heat-shocked cells of S. pombe appears to be more similar to the one observed in higher eukaryotes than that in S. cerevisiae. The SSP1 gene contains two methionine codons in the region predicted to encode a mitochondrial targeting signal sequence of its protein (Ssp1) and the stretch between the two methionine codons is capable of forming stem-loop structures. Both of the two methionine codons were confirmed to function as translational initiators in vitro. A possible mechanism is proposed for the response of the SSP1 gene towards heat-shock by the differential initiation of its transcription and translation. PMID- 1923817 TI - Demonstration of a divergent transcript from the bidirectional heavy chain immunoglobulin promoter VH441 in B-cells. AB - The mouse heavy chain immunoglobulin promoter VH441 can lead in vitro to bidirectional transcription, due to a symmetrical organization of immunoglobulin heavy chain promoters with two TATA-like sequences bracketing the upstream promoter element ATGCAAAT (the so called octamer). We demonstrate here that divergent transcription also occurs in vivo in mature B cells from a myeloma which expresses the VH441 gene and even from the spleen of BALB/c mice. The level of VH441 divergent transcript increases in the spleen of BALB/c mice after immunisation by beta-(1,6)-galactan, showing that it is expressed in B cells which actively transcribe the VH441 gene. The divergent transcript has been characterized: its major transcription start site was mapped within 33 base pairs from the divergent TATA-like region, it is unspliced and not polyadenylated. In the light of these results, the functions of the divergent transcript and the bidirectional promoter are discussed. PMID- 1923818 TI - Sequence conservation in the Saccharomyces and Kluveromyces GAL11 transcription activators suggests functional domains. AB - Efficient transcription of many Saccharomyces cerevisiae genes requires the GAL11 Protein. GAL11 belongs to a class of transcription activator that lacks a DNA binding domain. Such proteins are thought to activate specific genes by complexing with DNA-bound proteins. To begin to understand the domain structure function relationships of GAL11 we cloned and sequenced a homologue from the yeast Kluyveromyces lactis, Kl-GAL11. The two predicted GAL11 proteins show high overall amino acid conservation and an unusual amino acid composition including 18% glutamine, 10% asparagine (S. cerevisiae) or 7% (K. lactis), and 8% proline (K. lactis) or 5% (S. cerevisiae) residues. Both proteins have runs of pure glutamines. Sc-GAL11 has glutamine-alanine runs but in Kl-GAL11 the alanines in such runs are replaced by proline and other residues. The primary sequence similarity is reflected in functional similarity since a gal11 mutation in K. lactis creates phenotypes similar to those seen previously in gal11-defective S. cerevisiae. In addition, Kl-GAL11 complements a gal11-defect in S. cerevisiae by partially restoring induction of GAL1 expression, growth on nonfermentable carbon sources, and phosphorylation of GAL4. PMID- 1923819 TI - Coregulation of the Kluyveromyces lactis lactose permease and beta-galactosidase genes is achieved by interaction of multiple LAC9 binding sites in a 2.6 kbp divergent promoter. AB - The coregulated genes LAC4 and LAC12 encoding beta-galactosidase and lactose permease, respectively, are responsible for the ability of the milk yeast Kluyveromyces lactis to utilise lactose. They are divergently transcribed and separated by an unusually large intergenic region of 2.6 kbp. Mapping of the upstream border of the beta-galactosidase gene (LAC4) promoter by introduction of mutations at the chromosomal locus showed that LAC4 and LAC12 share the same upstream activation sites (UAS). The UASs represent binding sites for the trans activator LAC9, a K. lactis homologue of GAL4, conforming to the consensus sequence 5'-CGG(N5)A/T(N5)CCG-3'. Two binding sites are located in front of each of the genes at almost symmetrical positions. beta-galactosidase activity measurements as well as quantitation of LAC4 and LAC12 mRNA levels demonstrated that all four sites are required for full induction. LAC4 proximal and a LAC12 proximal sites cooperate in activating transcription of both genes. These sites are more than 1.7 kbp apart and the distal site is located more than 2.3 kbp upstream of the respective start of transcription. Thus, the distance between interacting sites is larger than in any of the well characterised yeast promoters. The contribution to gene activation differs for individual binding sites and correlates with the relative affinity of LAC9 for these sites in vitro suggesting that LAC9 binding is a rate limiting step for LAC promoter function. PMID- 1923820 TI - The yeast RNA polymerase I promoter: ribosomal DNA sequences involved in transcription initiation and complex formation in vitro. AB - Using an in vitro transcription system for Saccharomyces cerevisiae RNA polymerase I, we have analyzed Pol I promoter deletion mutants and mapped the boundaries of the promoter between positions -155 and +27. The 5'-boundary of the minimal core promoter capable of transcription initiation, however, was found to lie between -38 and -26. The 3'-deletion extending to -2 and -5 still allowed some transcription, suggesting that the positioning of Pol I is directed by upstream sequences. The results of in vitro analysis of linker scanning mutants (LSMs) combined with the deletion analysis showed that the promoter consists of three domains: two essential core domains (I: -28 to +8 and II: -76 to -51) and a transcription modulating upstream domain (III: -146 to -91). These results are in general agreement with those obtained in vivo (1). Using a template competition assay we also analyzed these mutant promoters for their ability to form a stable preinitiation complex. We found that the ability of 5'-deletion mutants to sequester an essential factor(s) correlates with their transcriptional activity. In contrast, several 3'-deletions and some LSMs in domain I and II decrease transcription activity greatly without significantly decreasing competition ability. The results indicate that the stimulatory function of domain III is achieved through its interaction with an essential transcription factor(s), although the other domains also participate in this interaction, perhaps directly or through another protein factor. PMID- 1923821 TI - Regulatory elements and DNA-binding proteins mediating transcription from the chicken very-low-density apolipoprotein II gene. AB - The chicken Very-Low-Density Apolipoprotein II (apoVLDL II) gene is specifically expressed in liver in response to estrogen. In this study, we performed a functional analysis of the 300-base pair region immediately 5' to the gene by gene transfer of chloramphenicol acetyl transferase (CAT) constructs into chicken embryonic hepatocytes (CEH). Two estrogen response elements (EREs) could be distinguished which together form a potent estrogen response unit. Stimulation of transient expression by co-transfection with a plasmid expressing rat C/EBP confirmed that a similar protein in chicken liver may be involved in apoVLDL II transcription. In vitro DNaseI footprinting and band-shift analysis with liver, oviduct and spleen nuclear extract revealed the tissue distribution of the proteins binding to the promoter region. A liver-specific protein bound to multiple sites of which some resembled the recognition sequence of the CCAAT/Enhancer binding protein, C/EBP. Of the other proteins binding to the apoVLDL II promoter, one was identified as the liver-specific LF-A1 by mobility shift analysis, using purified bovine LF-A1, and another as the general COUP transcription factor, using an antiserum against the human COUP-TF. PMID- 1923822 TI - Probing the activation of the replicative origin of broad host-range plasmid R1162 with Tus, the E.coli anti-helicase protein. AB - The E.coli Tus protein is an anti-helicase involved in the termination of chromosome replication. The binding site for this protein, ter, was cloned into derivatives of the broad host-range plasmid R1162. The ter site caused the orientation-specific termination of plasmid replication fork movement in cell extracts containing Tus. Plasmids were constructed so that two sites for initiation of R1162 replication flanked the iteron-containing domain of the origin. In these plasmids, the site next to the AT-rich region within the iteron containing domain was more active. In addition, when ter was placed between the more active site and the iterons, initiation of replication from this site was specifically inhibited. The data support a model for entry of the essential, plasmid-encoded helicase at one side of the direct repeats, and for its movement primarily in one direction away from these repeats to activate the initiation sites for DNA replication. PMID- 1923823 TI - Characterization of a DNA binding activity in DNAse I hypersensitive site 4 of the human globin locus control region. AB - A portion of the beta-globin Locus Control Region (LCR), which included DNAse I hypersensitive site 4 (HS4), was analyzed for its interactions with nuclear extracts and its contribution to LCR activity in a functional assay. In gel retardation assays, a short fragment from HS4 formed complexes with nuclear extracts from both erythroid and nonerythroid cells, and a core protected sequence 5'GACTGGC3' was revealed by DNAse I protection and methylation interference studies. This sequence resembles the binding sites of CCAAT-family members. Purified CP-2 but not CP-1 was shown to bind this HS4 sequence in a gel shift reaction, suggesting that the HS4 binding activity shares some sequence specificity with the CCAAT-factor family. Utilizing a transient expression assay in murine erythroleukemia cells, steady-state RNA levels were measured from pairs of LCR constructs linked to distinguishable beta-globin reporter genes. A short DNA fragment from HS4 which included the binding site for this novel binding activity accounted for most of the contribution to high level expression made by the entire HS4 region. PMID- 1923824 TI - PCR walking from microdissection clone M54 identifies three exons from the human gene for the neural cell adhesion molecule L1 (CAM-L1). AB - Microdissection has proved to be a powerful tool in the construction of libraries from specific chromosome segments (11) which are poorly covered by existing RFLP markers. Microclones also represent starting points for finding genes of interest. However, their length (100 to 200 bp) can make their use as probes problematic and identifying them as coding sequence is difficult. We report here that microclones can be extended in vitro by a modified version of our original PCR walking method (10) which utilises oligo-cassettes and the solid phase biotin/streptavidin separation system. We have extended the microclone M54, derived by dissection from Xq27.2 to proximal Xq28 (12), in both directions for approximately 700 bp. Direct sequencing of these products revealed that M54 was located within an intron of the human gene encoding the neural cell adhesion molecule L1 (CAM-L1) which has been recently mapped to Xq28 (13). The extension of M54 also identified three exons of this gene. This information allowed subsequent amplification of a 2.4 kb cDNA molecule from fetal human brain mRNA which encodes most of human CAM-L1. Sequencing of this cDNA revealed a high degree of sequence conservation with the mouse homologue (14). This is the first description of extension of a human derived microclone by PCR mediated walking within total human genomic DNA. These results show that anonymous DNA sequences may be extended into coding or any sequence. PMID- 1923825 TI - The core element of the EcoRII methylase as defined by protease digestion and deletion analysis. AB - Binding of the EcoRII DNA methyltransferase to azacytosine-containing DNA protects the enzyme from digestion by proteases. The limit digest yields a product having a Mr on SDS-PAGE 20% less than the intact protein. The N terminus of the tryptic digestion product was sequenced and found to be missing the N terminal 82 amino acids. Under the conditions used unbound enzyme was digested to small peptides. Protection of the enzyme from protease digestion implies that the enzyme undergoes major conformational changes when bound to DNA. The trypsin sensitive region of the EcoRII methyltransferase occurs prior to the first constant region shared with other procaryotic DNA(cytosine-5)methyltransferases. To determine if this region played a role in substrate binding or specificity, N terminal deletion mutants were studied. Deletion of 97 amino acids resulted in a decrease of enzyme activity. Further deletions caused a complete loss of activity. Enzyme deleted through amino acid 85 was purified and found to have the same specificity as wild type however there was an increase in Km for both S adenosylmethionine (AdoMet) and DNA of 27 and 18 fold respectively. The N terminus of the EcoRII methylase, although a variable region present in many procaryotic DNA(cytosine-5)methylases, plays no role in determining enzyme specificity, although it does contribute to the interaction with both AdoMet and DNA. PMID- 1923826 TI - Evidence that genomic and antigenomic RNA self-cleaving elements from hepatitis delta virus have similar secondary structures. AB - The two sequences that define the self-cleaving elements from the genomic and antigenomic RNA of hepatitis delta virus were folded into secondary structures with similar features. Evidence in support of the two models was obtained from limited ribonuclease digestion of genomic and antigenomic RNA fragments containing the sequence 3' of the cleavage site. Under conditions where the rates of self-cleavage are enhanced by addition of 5 M urea (2-10 mM Mg2+ at 37 degrees C), ribonucleases T1, U2, A and V1 generated digestion patterns consistent with the proposed RNA structures. The evidence for a relatively stable structure in urea when Mg2+ is present suggests that denaturant-enhanced rates of self cleavage could result from destabilization of competing inactive structures. PMID- 1923828 TI - Completion of the genome sequence of Rift Valley fever phlebovirus indicates that the L RNA is negative sense and codes for a putative transcriptase-replicase [corrected]. PMID- 1923827 TI - Common sets of nuclear factors binding to the conserved promoter sequence motif of two coordinately regulated ER protein genes, GRP78 and GRP94. AB - The GRP78 and GRP94 are two constitutively expressed ER resident proteins that are coordinately induced in response to stress conditions. The control of their induction is at the transcriptional level. We have previously demonstrated that the GRP78 and the GRP94 promoters share a common regulatory domain which is highly conserved. We report here that within this 36 bp promoter region is a CG/CAAT and a GC-rich sequence motif which are important for basal level and induced expression of the gene. Gel mobility shift assays with HeLa nuclear extracts and the conserved element from GRP78 and GRP94 show two shared, specific protein-DNA complexes. By ultraviolet cross-linking, the sizes of the proteins labeled in the slower-migrating complex are 210-, 110-, a doublet at 90/92- and 70 kD, and in the faster-migrating complex, protein species of about 55 kD. The formation of the second complex can be inhibited by competition with the coding strand of the conserved GRP element in a sequence specific manner. In addition, the Ku autoantigen which is abundant in HeLa cell extracts also binds. The sizes of the nuclear factors binding to the GRP78 and GRP94 conserved promoter elements are strikingly similar, providing further evidence that the two genes are coordinately regulated by common trans-acting factors. PMID- 1923829 TI - Sequence of 5.8S ribosomal RNA in the mosquito, Culex tritaeniorhynchus. PMID- 1923830 TI - Nucleotide sequence of a 23S and a 5S-like rRNA gene from the thermophilic Bacillus sp. strain PS3. PMID- 1923831 TI - Nucleotide sequence of a small subunit ribosomal RNA (16S-like rRNA) gene from Entamoeba histolytica: differentiation of pathogenic from nonpathogenic isolates. PMID- 1923832 TI - Complete nucleotide sequence of hepatitis delta virus RNA in Japan. PMID- 1923834 TI - A fast procedure for yeast DNA purification. PMID- 1923833 TI - Direct cloning of sequence tagged microsatellite sites by DNA affinity chromatography. PMID- 1923835 TI - Dinucleotide repeat polymorphism at the D16S288 locus. PMID- 1923836 TI - A highly polymorphic minisatellite (pMS627) on chromosome 14 (D14S44). PMID- 1923837 TI - Dinucleotide repeat polymorphism (D16S285) on human chromosome 16. PMID- 1923838 TI - Dinucleotide repeat polymorphism of D15S10 in the Prader-Willi chromosome region (PWCR). PMID- 1923839 TI - Tetranucleotide repeat polymorphism at the HPRT locus. PMID- 1923840 TI - Trinucleotide repeat polymorphism at the CRYG1 locus. PMID- 1923841 TI - A dinucleotide repeat polymorphism at the Kallmann locus (Xp22.3). PMID- 1923843 TI - P3: human environment. Part (II): Organising the nation's health. PMID- 1923844 TI - Hygiene in birthing pools. PMID- 1923845 TI - NHS trusts. Can we trust the trusts? PMID- 1923847 TI - NHS trusts. Leading the way. Interview by Bernadette Friend. PMID- 1923846 TI - NHS trusts. Riding the wave. PMID- 1923848 TI - NHS trusts. Holding out. PMID- 1923849 TI - The battle for health ratings. PMID- 1923850 TI - Once bitten.... PMID- 1923842 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1923851 TI - Choosing competence. PMID- 1923852 TI - Education. A matter of degree. PMID- 1923853 TI - A preventable tragedy. PMID- 1923854 TI - The old man's friend? PMID- 1923855 TI - Just four questions. PMID- 1923857 TI - Just testing? PMID- 1923856 TI - The prevalence of skin problems beneath the breasts of in-patients. AB - The prevalence of sore skin beneath the breasts has not been evaluated previously. One hundred and thirty-one wards in one district were visited, and 11.2% of all adult female patients either had an active lesion or one that had healed during her current admission. The patients tended to be in wards for the elderly or mentally ill, often suffering illnesses which affected their functional ability. It is estimated that approximately 2% of all senile admissions will develop this problem in the first six days. PMID- 1923858 TI - Nursing and the law. Compensation matters. PMID- 1923859 TI - Mental health. Special hospitals. Therapy versus custody. PMID- 1923860 TI - Mental health. Special hospitals. Involving the family. PMID- 1923861 TI - Mental health. Special hospitals. Opinion. PMID- 1923862 TI - Research module--R2: focusing on research knowledge. Part (ii): Rubbing shoulders with research. PMID- 1923863 TI - Venepuncture: further pointers for safe practice of the technique. PMID- 1923864 TI - The hidden problem. PMID- 1923866 TI - Children first. PMID- 1923865 TI - Checking out drugs. PMID- 1923867 TI - Changing rhythm. PMID- 1923868 TI - Are you obsessed with it? PMID- 1923869 TI - Dealing with dependency. PMID- 1923870 TI - Dependency problems. Alcohol-induced head injury. PMID- 1923872 TI - Sickle cell in pregnancy. PMID- 1923871 TI - Adolescent needs. Care study. PMID- 1923874 TI - Out-of-hospital defibrillation scheme. PMID- 1923873 TI - Systems of life. Reproductive system--Part 2. PMID- 1923875 TI - Attendance at A&E departments. PMID- 1923877 TI - The modern lepers. PMID- 1923876 TI - Management. Time to go home. Interview by Daloni Carlisle. PMID- 1923878 TI - Toronto transfer. PMID- 1923879 TI - Health visitors' supplement. One big happy family? PMID- 1923880 TI - Health visitors' supplement. A healthy future? PMID- 1923882 TI - Health visitors' supplement. A consummate professional. Interview by Sue Smith. PMID- 1923881 TI - Health visitors' supplement. For their own good. PMID- 1923883 TI - R2: focusing on research knowledge. Part (I): sources of knowledge. PMID- 1923884 TI - Insurance cover against HIV infection. PMID- 1923885 TI - A breathtaking development. PMID- 1923886 TI - Pay as you learn. PMID- 1923887 TI - Major muddle? PMID- 1923888 TI - Breast advice. PMID- 1923889 TI - Best foot forward. PMID- 1923890 TI - Security. Making work safe. PMID- 1923891 TI - Security. Harrogate hospital watch. PMID- 1923892 TI - Security. A lesson learnt. PMID- 1923893 TI - AIDS. Family matters. PMID- 1923894 TI - Brief encounter. PMID- 1923895 TI - Accidents will happen. PMID- 1923896 TI - Making sense of ... split skin graft donor sites. PMID- 1923897 TI - The causes of obstetric accidents. PMID- 1923898 TI - Implications of offering general health checks. PMID- 1923899 TI - Using caffeine for headache pain. PMID- 1923901 TI - Nurse education. Too much education...? PMID- 1923900 TI - Arts in action. Primary colour. PMID- 1923902 TI - Nurse education. How to ... get the most out of project work. PMID- 1923903 TI - Theatre nursing. Operation reassurance. PMID- 1923904 TI - Pain after day surgery. PMID- 1923905 TI - The effect of the level of dietary corn oil on mouse skin carcinogenesis. AB - To investigate the effects of two levels of dietary corn oil on tumorigenesis, semipurified diets containing 5% or 10% corn oil were fed during the promotion stage of a mouse skin carcinogenesis model. Sencar mice were initiated with 10 nmol dimethylbenz[a]anthracene (DMBA) and promoted with either 1 microgram 12-O tetradecanoylphorbol-13-acetate (TPA) or 40 mg benzoyl peroxide twice weekly for 24 or 52 weeks, respectively. No significant differences in kilocalories of food consumed or body weights were observed between the diet groups during the study. Fatty acid profiles of the epidermal phospholipids reflected dietary fat intake. For example, high levels of linoleate and low levels of arachidonate were found in the phosphatidylcholine fraction from mice fed the 10% corn oil diet compared with 5% corn oil. When the diets were fed during TPA promotion, the papilloma incidence after 11 weeks of treatment for the 5% corn oil group was 77% and 37% for the 10% corn oil group. By 15 weeks of TPA treatment, papilloma incidence between the diet groups was similar, and later, carcinoma incidence and yield were not different between the two groups. For the animals treated with benzoyl peroxide, there was only a slight but not significant difference in papilloma and carcinoma appearance. In parallel studies, ornithine decarboxylase activity, vascular permeability, hyperplasia, and prostaglandin E2 (PGE2) levels were elevated in the epidermis after promoter treatment, but only hyperplasia and PGE2 synthesis tended to reflect the dietary effects on tumor appearance. These data suggest that the quantity of dietary corn oil at the two levels tested, 5% and 10%, altered epidermal phospholipid fatty acid composition and PGE2 levels and had modest effects on the modulation of tumorigenesis in this skin model. PMID- 1923906 TI - Ethanol consumption and DMBA-induced mammary carcinogenesis in rats. AB - In this study, we report that chronic ethanol intake at 20% of calories can enhance the initiation stage and at 15% of calories can enhance the promotion stage of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in female Sprague-Dawley rats. Ethanol consumption at 20% of calories by female rats from 25 to 53 days of age was associated with a significant increase in terminal end bud (TEB) structures and a significant decrease in alveolar bud structures of the normal mammary gland. In addition to changes in mammary gland morphology, ethanol consumption at 20% of calories also was associated with a significant increase in incorporation of [3H]thymidine into mammary DNA and a significant increase in the DNA-labeling index of mammary TEB. Therefore, specific ethanol intakes can enhance DMBA-induced mammary tumorigenesis. The enhancement of the initiation stage partly may be explained by alterations in the structural development of the normal rat mammary gland that increase susceptibility to chemically induced mammary tumorigenesis. PMID- 1923907 TI - Suppressive effect of wasabi (pungent Japanese spice) on gastric carcinogenesis induced by MNNG in rats. AB - Dietary habits have been causally implicated in gastric carcinogenesis, whereas minor dietary items may also play a part. Wasabi is a popular pungent spice in Japanese meals. In this study the effect of wasabi on N-methyl-N'-nitro-N nitrosoguanidine (MNNG)-induced gastric carcinogenesis was studied in rats. Wistar WKY male rats received drinking water containing 50 micrograms/ml of MNNG or tap water alone and a basal diet (PCE-2) or PCE-2 containing 10% (wt/wt) of wasabi powder for 40 weeks. Thus, three groups were completed as MNNG + PCE-2 (n = 30), MNNG + wasabi (n = 30), and tap water + wasabi (n = 30). At autopsy, nine rats (30%) had seven glandular stomach tumors (2 adenocarcinomas, 2 adenomatous polyps, and 3 adenomatous glandular hyperplasias) and three duodenal adenocarcinomas in the MNNG + PCE-2 group, whereas in the MNNG + wasabi group, two rats (7%) had one forestomach epidermoid cyst and one duodenal carcinosarcoma (corrected chi 2 = 4.63, p less than 0.05 for incidences of glandular stomach tumors between 2 groups). In addition, two rats had microscopic atypical glands in the MNNG + PCE-2 group. There was no tumor in the tap water + wasabi group. These results indicated that glandular stomach carcinogenesis induced by MNNG was suppressed by the administration of wasabi. PMID- 1923908 TI - Inhibitory effects of Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice. AB - Topical application of Nigella sativa and Crocus sativus extracts (common food spices) inhibited two-stage initiation/promotion [dimethylbenz[a]anthracene (DMBA)/croton oil] skin carcinogenesis in mice. A dose of 100 mg/kg body wt of these extracts delayed the onset of papilloma formation and reduced the mean number of papillomas per mouse, respectively. The possibility that these extracts could inhibit the action of 20-methylcholanthrene (MCA)-induced soft tissue sarcomas was evaluated by studying the effect of these extracts on MCA-induced soft tissue sarcomas in albino mice. Intraperitoneal administration of Nigella sativa (100 mg/kg body wt) and oral administration of Crocus sativus (100 mg/kg body wt) 30 days after subcutaneous administration of MCA (745 nmol x 2 days) restricted tumor incidence to 33.3% and 10%, respectively, compared with 100% in MCA-treated controls. PMID- 1923909 TI - Therapeutic drug monitoring of cyclosporine-lipoprotein levels. AB - Cyclosporine therapy is complicated by nephrotoxicity that is not predicted by drug levels. In this study serial trough blood samples were obtained from 11 allogeneic marrow transplant recipients after initiation of intravenous cyclosporine 2 mg/kg every 12 hours for a period extending 4 weeks after transplantation. Renal dysfunction, assessed by an increase in serum creatinine levels to twice baseline values or when greater than 175 mumol/L, was found in four patients. No associations between renal dysfunction and cyclosporine levels in whole blood, total plasma, or lipoprotein fractions were found. The ratios of maximum and mean high-density low-density lipoprotein cyclosporine concentrations were greatest in patients with renal dysfunction (p less than 0.001). The data suggest therapeutic drug monitoring of cyclosporine in various biologic fluids does not predict onset of drug-associated renal dysfunction. However, the relative role of high-density to low-density lipoprotein transport of cyclosporine may provide an index of renal functional changes associated with the agent. PMID- 1923910 TI - Postinduction carbamazepine clearance in an adult psychiatric population. AB - The objective of this study was to describe the postinduction clearance of carbamazepine (CBZ) in adult psychiatric patients by population pharmacokinetic analysis using the NONMEM program. Specifically, an estimate of CBZ clearance and insight into the effect of common patient characteristics on clearance were sought. Steady-state trough CBZ serum concentrations, CBZ dosing history, concomitant drug administration, and other data from 45 patients were collected retrospectively. A one-compartment model with first-order absorption and first order elimination was used, with absorption rate, bioavailability, and volume of distribution fixed to literature values. No evidence was found that race, sex, age, ethanol use, smoking, and concomitant lithium significantly affected CBZ clearance. In the final model, clearance was based on lean body weight. The coefficient of variation for clearance estimates was 16.5%. Residual variability was modest. Estimates for volume of distribution, rates of absorption and elimination, and bioavailability could not be pursued rigorously. Although these results may assist in understanding CBZ disposition in this population, their general clinical application should be approached with caution. PMID- 1923911 TI - The efficacy of nutrition support in infected patients with chronic renal failure. AB - Patients with chronic renal failure are at considerable nutritional risk due to restricted diets, poor intake, and dialysis-related protein losses; therefore, they often require specialized nutrition support. It is difficult, however, to gauge the success of the intervention, since the gold standard nitrogen balance cannot be easily employed. We examined the usefulness of three visceral proteins, insulinlike growth factor 1 (IGF-1), fibronectin (FBN), and prealbumin (PA), as markers of nutrition support efficacy in patients with chronic renal failure. Fourteen patients receiving enteral (1) or parenteral (13) nutrition were studied for 7-28 days. The six males and eight females attained intakes of protein and nonprotein energy of 1.3 +/- 0.3 (mean +/- SD) g/kg/day and 34 +/- 6 kcal/kg/day, respectively. Blood samples taken on days 1, 4, 7, 14, 21, and 28 were assayed for IGF-1, FBN, and PA concentrations. Protein levels were correlated with cumulative nonprotein energy and protein intake. Concentrations of IGF-1 at baseline (0.90 +/- 0.48 U/ml) rose significantly by day 4 (1.35 +/- 0.78 U/ml) and remained significantly above baseline at days 7 (1.44 +/- 0.68 U/ml), 14 (1.63 +/- 1.05 U/ml), and 28 (1.59 +/- 0.98 U/ml). Baseline FBN (113 +/- 53 micrograms/ml) and PA (15.3 +/- 7.8 mg/dl) concentrations rose significantly by day 28 (FBN, 163 +/- 51 micrograms/ml; PA, 24.6 +/- 19.0 mg/dl). The PA concentrations correlated significantly with cumulative nonprotein calories and cumulative protein intake (r = 0.37, p less than 0.01; r = 0.43, p less than 0.01, respectively). Both IGF-1 and PA show promise as markers of nutrition support efficacy in this complex patient population. PMID- 1923912 TI - The disposition of alfentanil in neonates with respiratory distress. AB - The disposition of continuous infusion alfentanil was evaluated in 13 mechanically ventilated neonates (gestational age 37.6 +/- 2.4 wks) with hyaline membrane disease (n = 7) or persistent pulmonary hypertension of the newborn (n = 6). Alfentanil was administered as a loading dose 8 micrograms/kg, followed by a variable-rate continuous infusion (maximum 10 micrograms/kg/hr; minimum 2.5 micrograms/kg/hr) for 27 hours. Serial plasma samples were obtained for pharmacokinetic analysis. Noncompartmental pharmacokinetic analysis of the data revealed the following estimates (mean +/- SD): total-body clearance 3.24 +/- 2.23 ml/kg/minute, volume of distribution 0.54 +/- 0.21 L/kg, and elimination half-life 4.14 +/- 2.58 hours. A significant effect of alfentanil plasma concentration on total-body clearance was found (r = -0.75; p = 0.02), suggesting nonlinear pharmacokinetics. No correlation was seen between total-body clearance and alfentanil dose (r = -0.37; p = 0.32). The results suggest that a larger dose proportionality study is required to determine the linearity or nonlinearity of alfentanil pharmacokinetics in neonates. PMID- 1923913 TI - The influence of heparin on the prothrombin time. AB - We studied the effect of known concentrations of heparin on the prothrombin time (PT) in patients receiving warfarin and in controls who were not anticoagulated. Plasma from the subjects and controls was serially diluted with known concentrations of heparin, and PT was measured. Linear regression of heparin concentration versus percentage change in PT resulted in r = 0.86 in the warfarin group and r = 0.72 in the control group. The warfarin group was more sensitive to the effects of heparin than the control group, as manifested by a steeper slope of the regression line (p less than 0.001). Over the therapeutic range of heparin concentration (0.2-0.4 units/ml), the 95% prediction interval of the percentage change in PT was -6-12% at 0.2 units/ml, and 2-20% at 0.4 units/ml in the warfarin group. These results demonstrate a strong relationship between the heparin concentration in plasma and the percentage change in the PT. This effect should be considered when adding warfarin to the regime of patients receiving heparin therapy. PMID- 1923914 TI - Ticlopidine: a new antiplatelet agent for cerebrovascular disease. AB - Ticlopidine is a new prototype antiplatelet drug chemically unrelated to currently available agents. It causes an alteration in platelet membrane reactivity to a variety of aggregating stimuli and a marked prolongation of bleeding time, the mechanism of which remains unclear. Two major phase III multicenter trials, the ticlopidine-aspirin stroke study (TASS) and the Canadian American ticlopidine study (CATS) reported that the agent may reduce the occurrence of stroke, myocardial infarction, or vascular death in patients of both sexes who have had recent cerebral ischemia. Ticlopidine has been well tolerated in preliminary studies, with the most commonly described adverse effects being rash and gastrointestinal complaints. The most important adverse effect is neutropenia, which was reported in both TASS and CATS, approximating a frequency of 0.9% and 0.8%, respectively. Ticlopidine holds considerable promise as adjunctive therapy in selected patients. PMID- 1923915 TI - Urinary tract infections in childhood: definition, pathogenesis, diagnosis, and management. AB - Urinary tract infections in childhood are defined as significant bacterial growth in urine obtained by bladder catheterization, suprapubic aspiration, or several clean-voided specimens. In infants and young children they may be easily overlooked because of nonspecific symptoms. This leads to an underestimation of their true prevalence. The severity of these infections is a function of the balance between the various host defense mechanisms and the virulence of the microorganism. The assessment of symptomatic infants and children requires a complete radiographic evaluation (renal ultrasound and voiding cystourethrogram), because of the high frequency of anatomic abnormalities, particularly vesicoureteral reflux. The major issues in the management of children with uncomplicated lower urinary tract infections are whether a single dose or short course of therapy is as efficacious as the conventional 7-10 days, and whether asymptomatic bacteriuria requires treatment. PMID- 1923916 TI - Absorption of oral ciprofloxacin in a patient with cardiogenic shock. AB - Congestive heart failure and cardiogenic shock can alter the absorption process of some drugs. The absorption of ciprofloxacin has been studied in several disease states, but the effect of cardiogenic shock on its absorption is unknown. A 63-year-old man had a large myocardial infarction complicated by cardiogenic shock. When he began taking ciprofloxacin for pneumonia, he had renal and cardiac failure. Ciprofloxacin 500 mg was administered every 24 hours by nasogastric tube. Blood samples were collected 5 minutes prior to the second dose (20 hrs after the initial dose) and then regularly until 11 hours after the dose. Samples were analyzed using high-performance liquid chromatography. The trough concentration 20 hours after the initial dose was 3.7 micrograms/ml, and the serum concentrations after the second dose went from 5.6 to 4.94 micrograms/ml over the 11-hour sampling period. The peak concentration of 5.6 micrograms/ml occurred within 30 minutes after ciprofloxacin administration. It can be concluded from this case study that ciprofloxacin was adequately absorbed in this patient with multiple organ failure. PMID- 1923917 TI - Buspirone in the treatment of posttraumatic stress disorder. AB - Three patients with a DSM-III-R diagnosis of posttraumatic stress disorder were successfully treated with buspirone in final maximum dosages ranging from 35-60 mg daily. The onset of clinical efficacy ranged from 5-29 days. Symptoms that improved included anxiety, insomnia, flashbacks, and depressed mood. Patients experienced no side effects. Serotonin partial agonist effects are a possible mechanism underlying buspirone's efficacy. PMID- 1923918 TI - Interaction of dexamethasone with phenytoin. AB - Phenytoin and dexamethasone are frequently administered concurrently to prevent consequences of central nervous system pathology. Limited and conflicting data are available regarding an interaction between the agents. A patient receiving dexamethasone required a daily phenytoin dose of greater than 10 mg/kg to maintain the phenytoin serum concentration within the usual therapeutic range. The concentration increased by nearly 300% after dexamethasone was discontinued. PMID- 1923919 TI - Elevated phenytoin concentration caused by sampling through the drug administration catheter. AB - Elevated phenytoin concentrations are a problem due to the toxic effects that can result. When an elevated concentration is reported, it is important to determine the validity of the report because therapeutic action may include withholding further doses. If the concentration is falsely elevated, the potential for seizure activity as it falls is inherent. Assessing validity involves considering laboratory error and assays of blood samples drawn from the wrong patient. The capacity-limited biotransformation of phenytoin complicates the estimation of concentrations, making it more difficult to establish the accuracy of reported values. Our patient had a phenytoin concentration of 80.7 mg/L. It had been 13.4 mg/L the day before, and the patient received only an additional 400 mg prior to the reported high value. The pharmacokinetic team determined that the dose was administered through a triple-lumen catheter from which blood may have been withdrawn for phenytoin analysis the next day. Venous sampling 7 hours after the 80.7-mg/L value yielded a phenytoin concentration of 12.4 mg/L. Clinicians should consider this error potential in the differential evaluation of elevated concentration in apparently nontoxic patients. PMID- 1923920 TI - Neurotoxicity associated with ceftazidime therapy in geriatric patients with renal dysfunction. AB - Ceftazidime, a beta-lactamase-stable, third-generation cephalosporin, is widely used for the treatment of serious gram-negative infections. Neurotoxicity has rarely been associated with the drug; however, two of our patients developed ceftazidime-induced neurotoxicity that produced confusion, disorientation, agitation, generalized weakness, and myoclonus. In both patients these symptoms cleared with either discontinuation or reduction of the dosage of ceftazidime. This emphasizes the importance of adjusting the dosage of ceftazidime in patients with renal insufficiency. PMID- 1923921 TI - Central action of somatostatin analog, SMS 201-995, to stimulate gastric acid secretion in rats. AB - The effects of intracisternal and intravenous injections of the somatostatin analog, SMS 201-995, on gastric acid secretion were investigated in rats with pylorus ligation or gastric cannula. Intracisternal injection of SMS 201-995 induced a dose-related (0.1-0.3 microgram) and long-lasting stimulation of gastric acid output with a peak response at 3 h postinjection in conscious, pylorus-ligated rats. Intracisternal SMS 201-995 increased histamine levels in the portal blood, whereas plasma gastrin levels were not modified. Atropine, cimetidine and adrenalectomy abolished the stimulatory effect of intracisternal SMS 201-995 (0.3 microgram). SMS 201-995 (0.03 microgram), microinjected unilaterally into the dorsal vagal complex, increased gastric acid output in urethane anesthetized rats. SMS 201-995, injected intravenously at 0.5 microgram, did not alter gastric secretion, whereas higher doses (5-20 micrograms) resulted in a dose-related inhibition of gastric acid secretion in conscious pylorus ligated rats. These data indicate that SMS 201-995, a selective ligand for somatostatin-1 receptor subtype, induces a centrally mediated stimulatory effect on gastric acid secretion in rats. The central action involves the parasympathetic system, muscarinic and H2 receptors as well as adrenal-dependent pathways. PMID- 1923922 TI - Pentagastrin-stimulated DNA synthesis in mouse gut is influenced by the circadian system. AB - Gastrin is trophic for rodent gut mucosa. Proglumide, a competitive inhibitor of gastrin, can exert an antitrophic effect and can block pentagastrin-stimulated DNA synthesis. We have examined the influence of the circadian system on pentagastrin-stimulated DNA synthesis in the murine stomach (glandular and nonglandular stomach) and colon. We studied 224 male CD2F1 mice divided into four groups. Group A was ad lib fed (controls). Groups B, C, and D received 6-9 intraperitoneal injections of either NaCl, pentagastrin or pentagastrin + proglumide, at 8-h intervals prior to sacrifice. Mice from each group (A-D) were killed (by cervical dislocation) at 3-h intervals for 24 h. Incorporation of tritiated thymidine (DNA synthesis) was measured, and significant (p less than 0.001) circadian rhythms were found, which were not eliminated after treatment with either pentagastrin or pentagastrin + proglumide. DNA synthesis in the glandular stomach increased significantly after treatment with pentagastrin , but only during the span of time when DNA synthesis was increasing also in control mice; it had no effect at other times. Proglumide blocked the effect of pentagastrin only during the time of increasing DNA synthesis; it had no effect at other times. The identical regimen given at different times in the circadian cycle yielded significantly different results. In the intact animal, studies on the effects of various stimulators or inhibitors of DNA synthesis should be time qualified. PMID- 1923923 TI - Unchanged hypothalamic neuropeptide Y concentrations in hyperphagic, hypoglycemic rats: evidence for specific metabolic regulation of hypothalamic NPY. AB - Hypothalamic concentrations of neuropeptide Y (NPY), a potent central appetite stimulant, increase dramatically in food-restricted and insulin-deficient diabetic rats. This suggest that NPY may drive hyperphagia in these conditions, which are characterized by weight loss and insulin deficiency. To test the hypothesis that insulin deficiency and weight loss are specific stimuli to hypothalamic NPY, we measured NPY concentrations in individual hypothalamic regions in rats with hyperphagia caused by insulin-induced hypoglycemia. Groups of 8 male Wistar rats were injected with ultralente insulin (20-60 U/kg) to induce either acute hypoglycemia (7 h after a single injection) or chronic hypoglycemia (8 days with daily injections). In hypoglycemic rats, plasma insulin concentrations were increased 6- to 7-fold compared with saline-injected controls; food intake was significantly increased with acute and chronic hypoglycemia and weight gain was significantly increased in the chronically hypoglycemic group. NPY concentrations were measured by radioimmunoassay in 8 hypothalamic regions microdissected from fresh brain slices. NPY concentrations were not increased in any region in either acute or chronic hypoglycemia. NPY therefore seems unlikely to mediate hyperphagia in hyperinsulinemia-induced hypoglycemia, supporting the hypothesis that weight loss is a specific stimulus to hypothalamic NPY and that insulin deficiency may be the metabolic signal responsible. PMID- 1923924 TI - Extraction and immunochemical characterization of delta sleep-inducing peptide like material from the porcine pituitary and adrenal gland. AB - The naturally occurring forms of delta sleep-inducing peptide (DSIP) are not fully identified. In the present study, porcine pituitaries and adrenal glands were extracted in water, saline or acid under various conditions and immunoreactive DSIP (IR-DSIP) quantified by radioimmunoassay. The highest concentrations were measured in anterior pituitary extracts (40.8 +/- 2.6 ng/g tissue weight) recovered using water with aprotinin. However, high performance liquid chromatography (HPLC) indicated degradation of hydrophobic forms of IR DSIP in water extracts. Extraction in acetic acid including C18 Sep-Pak purification resulted in an elution profile of IR-DSIP in adrenal extracts with a major peak coeluting with synthetic DSIP [DSIP(1-9)], whereas anterior pituitary extract showed material of higher hydrophobicity. Approximately 30% of IR-DSIP in anterior pituitary as well as in adrenal gland extracts seemed to be glucosylated, as based on concanavalin A chromatography. One of the DSIP immunoreactive components by immunoblotting (molecular mass 25 kDa) was identified in both pituitary and adrenal gland extracts. In conclusion, several chromatographically distinct forms of IR-DSIP are present in the porcine pituitary and adrenal gland. IR material eluting as DSIP(1-9) is present in adrenal gland extract. The procedure and solution used for tissue extraction seem to be essential in order to obtain reliable elution positions on HPLC. PMID- 1923925 TI - Isolation of the neuropeptide SALMFamide-1 from starfish using a new antiserum. AB - We have raised antisera in rabbits to a conjugate of thyroglobulin and Lys-Tyr Ser-Ala-Leu-Met-Phe-NH2 (KYSALMFamide), a synthetic analog of the starfish neuropeptide S1 (Gly-Phe-Asn-Ser-Ala-Leu-Met- Phe-NH2). The sensitivity and specificity of two antisera (BL and SL) for S1 were established by testing the ability of S1 and structurally related peptides (SALMFamide-2 and various FMRFamide-related peptides) to displace iodinated KYSALMFamide from the serum antibodies in an RIA. Both antisera are sensitive to femtomolar amounts of S1. BL is highly specific for S1 but SL is not, since it is also able to detect femtomolar amounts of the FMRFamide-related peptides. We have used the BL antiserum in the RIA to monitor the purification of S1 immunoreactivity from radial nerve cord extracts of both Asterias rubens and Pycnopodia helianthoides. The partial amino acid sequence GFNSALM was obtained from automated Edman degradation sequencing of pure immunoreactive peaks from both species. PMID- 1923926 TI - Differential effects of DGAVP on acquisition and extinction of active avoidance behavior. AB - DGAVP facilitates consolidation and retrieval of active and passive avoidance behavior. In this study it was tested whether the long-term behavioral effects of DGAVP are the consequence of an initial increase in behavioral arousal during the learning phase. Animals that were preestimated in an open field test to be low active showed a lower number of conditioned avoidance responses (CAR's) during acquisition and extinction of a shuttle-box task than high active rats. DGAVP was administered 40 min prior to the 1st acquisition session. The immediate effect of DGAVP was a shift in the bell-shaped curve of the relation between arousal and performance (13); an increase in acquisition performance was observed with a low dose of DGAVP (0.1 microgram), while a decrease was found with a high dose of DGAVP (1 microgram). A dose-dependent inhibition of extinction was found in both low and high active animals. These results suggest an immediate effect of DGAVP on the rate of acquisition behavior, which may be a direct consequence of its arousing properties, and a long-term effect on extinction, indicating the formation of memory traces specific for vasopressin-related neuropeptides. PMID- 1923927 TI - Intracerebroventricular injection of arginine vasotocin induces elevation of blood pressure in anesthetized trout. AB - The present investigation assessed the ability of the neurohypophysial nonapeptide arginine vasotocin (AVT) to centrally regulate the cardiovascular activity in fish. Intracerebroventricular (ICV) injection of AVT (0.4 to 50 ng/kg b.wt.) in anesthetized trout resulted in a dose-related increase in blood pressure (BP) without any consistent changes in heart rate. For doses of AVT ranging from 2 to 50 ng/kg b.wt., BP remained elevated during at least 25 min after ICV injection. Systemic (intraarterial) administration of the same doses of AVT appeared to be less efficient than ICV injection, except for the highest dose (50 ng/kg) which evoked a similar rise in BP as that observed after ICV administration. In contrast to AVT, a high concentration of neuropeptide Y (10 micrograms/kg b.wt., ICV) caused only a slight increase of BP. The results suggest that AVT acts centrally to regulate BP in fish. These data, together with the widespread distribution of AVT-immunoreactive fibers and AVT binding sites in the brain, support the notion that, in fish, AVT may play neuromodulator and/or neurotransmitter functions. PMID- 1923928 TI - The effect of acutely administered beta-casomorphin derivatives on pentylenetetrazol-kindled mice. AB - Some of the Tyr-containing and desTyr beta-casomorphin derivatives were tested for their anticonvulsant action in pentylenetatrazol-kindled mice. It was demonstrated that some of these substances exert powerful action against kindled seizures, suggesting therapeutical usefulness. PMID- 1923929 TI - New analogs of the immunoregulatory PRP-pentapeptide. AB - To determine the role of consecutive amino acid residues in the immunoreactivity of the shortest active fragment of PRP, a series of analogs substituted by L alanine in successive positions of the peptide chain was synthesized. The immunological investigations were carried out in several models: the immune response to T-cell dependent antigen, SRBC (in vivo and in vitro) and to T-cell independent antigen, PVP in vitro. The immunotropic action of the peptide was, in addition, verified with respect to thymocytes forming autologous rosettes. The results of these experiments revealed immunotropic activity (in all tests) of the analog containing alanine instead of proline in position 5 of PRP-pentapeptide. PMID- 1923930 TI - Brain CCKA receptors mediate the colonic motor response to feeding in dogs. AB - The influence of central vs. peripheral administration of specific type A and type B CCK receptor antagonists (L364,718 and L365,260, respectively) on colonic motor hyperactivity induced by feeding and CCK8 was investigated in dogs with strain-gauge transducers implanted on the proximal and transverse colon. Intravenous injection of L364,718 (5 and 10 micrograms/kg) reduced by 26.2% and 80.1%, respectively, the 0-4-h postprandial increase in colonic motor index; at similar doses L365,260 had no effect. Intracerebroventricular administration of L364,718, at a dose (1 microgram/kg) not active by the IV route, significantly reduced (p less than 0.01) by 67.5% the feeding-induced colonic hyperactivity. In contrast, L365,260 (1-10 micrograms/kg ICV) injected was inactive. Increase in colonic motility produced by intravenous CCK8 infusion (1 microgram/kg/h) was suppressed by previous ICV and IV administration of L364,718 at doses of 1 and 10 micrograms/kg, respectively, while L365,260 was inactive at similar doses. It is concluded that CCK8 released after a meal is responsible for the postprandial increase in colonic motility and that these effects may be mediated through activation of central CCKA receptors. PMID- 1923931 TI - Pineal vasoactive intestinal peptide is reduced during the proestrous stage of the rat estrous cycle. AB - Immunoreactive levels of vasoactive intestinal peptide (IR-VIP) in the rat pineal gland were examined during the estrous cycle. IR-VIP was shown to be identical to the synthetic porcine material by its similarity in competitive binding studies, and by both gel filtration and high pressure liquid chromatography. Pineal IR-VIP decreased at early proestrus (0300 h, dark), partially as a function of the rise in serum estradiol levels. Although the functional role of VIP in the pineal remains to be clearly elucidated, these results suggest that it might be involved in the reproductive function of the female rat, and that estrogens could partially modulate its pineal concentration. PMID- 1923932 TI - Some characteristics of specific angiotensin II binding sites on bovine brain microvessel endothelial cell monolayers. AB - Angiotensin II (Ang II) binding sites were characterized in primary cultures of bovine brain microvessel endothelial cell (BMEC) monolayers. Binding of [3H]Ang II to BMECs was time dependent and saturable. Scatchard plot analysis of dose dependent [3H]Ang II binding revealed a single population of binding sites (Kd = 3.1 nM, Bmax = 52 fmoles/mg protein). Sarathrin, an Ang II antagonist, and saralsin, a partial agonist, inhibited [3H]Ang II binding to BMEC monolayers, whereas two unrelated peptides, bradykinin and arginine-vasopressin, had no effect on the specific binding of [3H]Ang II. At 37 degrees C, [3H]Ang II was internalized in BMECs and this uptake appeared to be saturable. Nanomolar concentrations of Ang II and saralasin stimulated [3H]thymidine uptake in serum free starved BMEC monolayers, corresponding to an increase in DNA synthesis. On the other hand, sarathrin had no effect on [3H]thymidine uptake. The affinity of the single population of Ang II of binding sites was consistent with the concentration range of Ang II actions demonstrated in several cell types including BMECs. The Ang II-mediated actions on DNA synthesis suggest that this peptide-hormone may possess growth regulating properties in BMECs through either surface or internal site interactions. Collective findings support the complex nature of Ang II in regulating vascular and nonvascular cell growth and permeability characteristics. PMID- 1923933 TI - Detection of Met-enkephalin in the CNS of the teleosts, Anguilla rostrata and Oncorhynchus kisutch. AB - Acid extracts of the brains of the American eel, Anguilla rostrata, and the coho salmon, Oncorhynchus kisutch, were screened for enkephalin-related products and dynorphin-related products. Following Sephadex G-50 column chromatography, a peak of Met-enkephalin-related immunoreactivity was detected near the total volume of the column for both species. No higher molecular weight forms of Met-enkephalin related material were detected, nor were any immunoreactive forms with antigenic determinants similar to mammalian dynorphin A(1-17), dynorphin A(1-8), dynorphin B(1-13) or alpha-neo-endorphin detected for either species. The enkephalin-sized immunoreactivity was further analyzed by reverse phase HPLC. For both species, a peak of authentic Met-enkephalin was detected. However, Leu-enkephalin, Met enkephalin-RGL and Met-enkephalin-RF were not detected by RIA in either species. In addition, no novel C-terminally extended forms of Met-enkephalin were detected in either species. Finally, opiate receptor binding activity was only found associated with the peak of immunoreactive Met-enkephalin. PMID- 1923934 TI - Sauvagine: inhibition of gastric acid secretion in rats. AB - Sauvagine (SV) powerfully inhibits gastric acid secretion by both the central and peripheral mechanisms. We examined whether adrenergic mechanisms or prostaglandin pathways might mediate the inhibitory action of SV on acid production in pylorus ligated rats. Adrenalectomy altered the extent of the SV suppressive effect, suggesting that adrenal-derived substances participate in the action of the peptide. Blockade of adrenergic receptors by propranolol did not modify the antisecretory effect of SV, while the alpha-adrenergic antagonist, phentolamine, and the dopaminergic antagonist, haloperidol, potentiated the gastric response to the peptide. The action of SV appeared to be independent of prostaglandin pathways. We conclude that the antiacid effect of SV may be mediated by the adrenal but probably not by adrenergic or prostaglandin mechanisms. PMID- 1923935 TI - Importance of the phenotypic state of vascular smooth muscle cells on the binding and the mitogenic activity of endothelin. AB - Smooth muscle cells of the rabbit aorta, when grown in vitro, express distinguishable forms of phenotypes (contractile and synthetic). On contractile cells, ET-1 specifically bound to a single class of high affinity (KD = 128 pM) and high capacity (Bmax = 66,000 sites/cell) binding sites. But, whereas affinity of [125I]-ET-1 was not significantly affected by phenotypic modulation, synthetic cells displayed a 10-fold lower [125I]-ET-1 binding capacity than contractile smooth muscle cells. Similarly, the mitogenic effect of ET-1 on smooth muscle cells was considerably lower for synthetic than for contractile cells. The ET-1 receptor on primary cells was recognized by sarafotoxin S6b and the different ET related peptides with an order of potency [ET-1 greater than S6b greater than ET 3 greater than Big ET-1 much greater than ET(16-21)] identical to that inducing smooth muscle cell growth. Therefore, these data indicate that the binding and the mitogenic effects of ET-1 on smooth muscle cells might be of different magnitudes depending on the phenotypic state of these cells. PMID- 1923936 TI - Localization of angiotensin II receptor subtypes in the rabbit adrenal and kidney. AB - The localization of subtypes of the angiotensin II receptor has been determined by autoradiographic techniques using iodinated angiotensin II and two nonpeptide antagonists that exhibit selective affinities. DuP 753 specifically displaces type 1 sites (AII-1) and PD123177 inhibits only type 2 sites (AII-2). The rabbit adrenal cortex contains predominately AII-1 sites and the few AII-2 sites that are present are nonuniformly distributed. In the rabbit kidney, the fibrous outer sheath contains exclusively AII-2 sites whereas the glomeruli of the renal cortex and the renal medulla exhibit only AII-1 sites. PMID- 1923937 TI - Characterization of large neuromedin-N using antisera towards regions of the neurotensin/neuromedin-N precursor. AB - Processing of the precursor to neurotensin/neuromedin-N was studied in brain and intestine from four mammalian species (dog, cat, guinea pig and rat) using previously characterized immunoassays for neurotensin and neuromedin-N, as well as newly developed assays towards the 35-44 sequence (P1) and the 70-85 sequence (P2) of the canine precursor. While neurotensin was the major product (approximately 98%) with neurotensin immunoreactivity in brain and ileum, a large molecular form of neuromedin-N was found to comprise 55-91% of the neuromedin-N activity in the ileum of these species and only 2-8% that in brain. Large neuromedin-N, which behaved as a single substance during multiple chromatographic steps, was found to cross-react in the assays for P1 and P2, indicating that this molecule extended at least from residues 40-148, neuromedin-N being located at its C-terminus. Western blots confirmed the results obtained by immunoassay. Partially purified preparations of large neuromedin-N from dog, cat and rat were also found to contract the isolated guinea pig ileum, exhibiting potencies near to that of neuromedin-N. These results indicate that tissue-specific storage of large neuromedin-N, a biologically active molecule with greater than 100 amino acids, occurs in these four mammals. PMID- 1923938 TI - Insatiable feeding evoked in rats by recurrent perfusion of neuropeptide Y in the hypothalamus. AB - Hyperphagic-like intake of food was determined in the unrestrained rat during the sustained elevation over time of neuropeptide Y (NPY) within the paraventricular nucleus (PVN) and surrounding hypothalamic regions. A single guide tube was implanted stereotaxically in each of 22 rats for localized, intermittent perfusions of a CSF vehicle, nondeprotected NPY(1-36) or native NPY. Each site in the PVN of the fully sated rat was perfused repeatedly over a 5.0-h interval by means of a standard push-pull cannula system at a rate of 20 microliters/min for 6.0 min in one of three concentrations: 0.2, 1.0 and 2.0 micrograms/min. Two perfusions of 1.0 micrograms/min NPY evoked an intake of 4.6 +/- 1.1 g of food over a 3.0-h period, whereas 4-7 and 8-15 perfusions of this concentration of NPY, distributed over 5.0 h, induced the sated rats to eat a total of 12.0 +/- 1.1 g and 33.2 +/- 3.0 g, respectively. During a fixed number of 10 hypothalamic perfusions distributed over 5.0 h, concentrations of 0.2 and 2.0 micrograms/min NPY caused a cumulative intake of food in the rats of 14.2 +/- 2.0 g and 31.7 +/- 3.3 g, respectively. Under each condition, parallel push-pull perfusions of either control solution in the same hypothalamic sites were without effect on feeding. During the 5.0-h interval of repeated perfusions, successive bouts of eating occurred with individual intakes of food reaching as high as 49.0 g, which exceeded by up to two-fold the entire daily consumption of food. However, ingestion of water was unaffected by perfusion of NPY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1923939 TI - Specific binding sites for pituitary adenylate cyclase activating polypeptide (PACAP) in rat cultured astrocytes: molecular identification and interaction with vasoactive intestinal peptide (VIP). AB - Molecular identification of the binding sites for pituitary adenylate cyclase activating polypeptide (PACAP) and the effect of vasoactive intestinal peptide (VIP) on the specific binding sites for PACAP in rat cultured astrocyte membrane preparations were investigated. Affinity cross-linking of astrocyte membrane preparations with [125I]PACAP27 showed the presence of a 60 kDa radiolabeled ligand-receptor complex. The labeling of this band was completely abolished in the presence of 10(-8) M or higher concentrations of unlabeled PACAP27. The molecular weight of this binding protein was estimated to be 57 kDa assuming an equimolar interaction of ligand and receptor in the 60 kDa complex. The labeling of [125I]PACAP27 binding to this binding protein was partly reduced by the addition of 10(-6) M VIP, but not by 10(-8) M. In the binding assay, VIP displaced the specific binding of [125I]PACAP27 at 10(-7) M or a greater concentration. Displacement of [125I]PACAP27 binding by unlabeled PACAP27 was analyzed in the presence or absence of 10(-6) M VIP. VIP at 10(-6) M reduced the maximal binding capacity (Bmax) of the high affinity binding site for PACAP27 by about 50% but did not alter the Bmax of the low affinity binding site. The dissociation constants (Kd) for both the high and low affinity binding sites were unaltered. These results indicate that PACAP binds to a 57 kDa membrane protein with high affinity and that VIP, at much higher concentrations, binds to this same binding site, suggesting that VIP mimics the biological action of PACAP in astrocytes at high concentrations. PMID- 1923940 TI - Epidermal growth factor and the nervous system. AB - Various growth factors and their receptors are present in the nervous system. This review focuses on the presence of epidermal growth factor (EGF) and its receptors in the central nervous system (CNS). Evidence indicates that EGF in the CNS is the result of local synthesis, by intrinsic and blood-derived macrophages, glial cells and neurons, and uptake from the peripheral blood through the circumventricular organs and probably also through the blood-brain barrier. Evidence is accumulating suggesting that EGF regulates a variety of CNS functions in a specific manner. EGF influences CNS growth, differentiation and maintenance (actions proposed to promote neural regeneration and cell survival following a variety of insults). EGF also induces neuromodulatory actions, affects the neuroendocrine system, and suppresses food intake and gastric acid secretion. Acute and chronic pathological processes, e.g., various cancers, stimulate the production and release of EGF in various cell systems. Monitoring of EGF by the CNS may participate in several neurological manifestations (e.g., appetite suppression, neuroendocrine alterations) frequently accompanying acute and chronic disease. EGF and transforming growth factor-alpha (TGF-alpha, a factor that binds to the EGF receptor with high affinity and induces the same biological signals as EGF) also may be involved in the promotion of malignancy in the CNS and in the neuropathogenesis of degenerative disorders. Thus evidence is accumulating concerning the neurophysiological or neuropathophysiological significance of EGF in the nervous system. PMID- 1923941 TI - N-acetyl-GRP(20-26)-O-CH3 reverses intracisternal bombesin-induced inhibition of gastric acid secretion in rats. AB - Intracisternal injection of 19 pmoles of bombesin in light-ether-anesthetized rats, five minutes after intracisternal vehicle, produced a 75% and 63% inhibition in gastric acid output and concentration, respectively, in 2-hour pylorus-ligated rats. Pretreatment of rats with the characterized peripheral bombesin antagonist N-acetyl-GRP(20-26)-O-CH3 (1 nmole) reversed the inhibitory effect of bombesin on gastric acid output and concentration. In contrast, the related bombesin antagonist N-acetyl-GRP-O-CH2-CH3 (1 nmole) was ineffective in this system. In urethane-anesthetized, acute gastric fistula rats infused with pentagastrin, intracisternal N-acetyl-GRP(20-26)-O-CH3 protected against the inhibition in gastric acid output produced by intracisternal bombesin (19 pmoles). Thus the recently characterized peripheral bombesin antagonist N-acetyl GRP(20-26)-O-CH3 also appears to be effective in antagonizing central bombesin induced inhibition in gastric acid secretion in two models. This represents a first report of a synthetic bombesin antagonist effective in reversing central bombesin-induced effects on gastric function. PMID- 1923942 TI - The anticonvulsive effect of BCH 325 is age dependent. AB - The two different experimental approaches which were applied to study the anticonvulsive effectiveness of BCH 325, a des-tyrosine derivative of bovine beta casomorphin-(5), in immature (22-day-old) and mature (7-week-old) female rats revealed that the peptide was able to protect mature females from electrically induced seizures and that it had no effect on pentylenetetrazol-induced convulsions. As opposed to this, immature animals were protected against chemically induced seizures but no effect was found using electrically induced seizures. PMID- 1923943 TI - Evaluation of 29 monoclonal and polyclonal antibodies used in the diagnosis of pituitary adenomas. A collaborative study from pathologists of the Club Francais de l'Hypophyse. AB - Fifteen polyclonal antibodies (pAbs) and 14 monoclonal antibodies (mAbs) directed against hGH, hPRL, beta hFSH, beta hLH, beta hTSH and alpha-subunit were assessed by five different laboratories on normal and adenomatous pituitary tissues. This study aims at providing pathologists with a selected panel of antisera suitable for diagnosis, and appreciating the interest of the recently introduced mAbs. All the anti-hGH Abs proved to be specific (3 pAbs and 4 mAbs); three mAb out of four gave a few false-negative reactions. Three out of six polyclonal anti-hPRL showed cross-reactivity with hGH; anti-hPRL mAbs gave a strong staining with no false negativity detected so far. MAbs proved to be more efficient for detecting glycoprotein hormones and alpha subunit than pAbs, which, in several cases, gave widespread cross-reactivity. This lack of specificity could explain the noticeable discrepancies reported so far in the appraisal of gonadotropic and somatoprolactinic adenomas. PMID- 1923945 TI - In situ hybridization in the study of pituitary tissues. AB - This presentation summarizes the use of in situ hybridization in the study of pituitary abnormalities. The basic techniques, technical problems and pitfalls in in interpretation and the application of in situ hybridization are discussed. PMID- 1923944 TI - Reverse hemolytic plaque assay. Electron microscopic observation of plaque forming single adenoma cells in GH producing adenomas. AB - In this study, 3 GH-producing adenomas were studied as materials to clarify the usefulness of electron microscopic investigation of plaque-forming single adenoma cells, and ultrastructural morphometric comparisons were made to determine whether some differences exist at the cytoplasmic organelle level between small plaque-forming cells and large plaque-forming cells. In two cases, the relative cytoplasmic volume density of Golgi apparatus and lysosomes were significantly greater and the diameter of seretory granules were significantly smaller in large plaque-forming cells compared to small plaque-forming cells. Moreover, in one of them, not only the diameter but also the cytoplasmic volume density of secretory granules were significantly smaller in large plaque-forming cells. These findings suggest a greater secretory granule synthesis and internal granule destruction, and faster granules secretion at an early stage of formation in large plaque forming cells compared with small plaque-forming cells. It became apparent through this study that electron microscopic investigation of plaque-forming single cells is practically useful since plasma membrane and cytoplasmic organelles were preserved well after processing for EM in most plaque-forming cells. PMID- 1923946 TI - Non-isotopic in situ hybridization with digoxigenin and alkaline phosphatase labelled oligodeoxynucleotide probes. Applications in pituitary gland. AB - We report the application of digoxigenin labelled oligonucleotide probes for the detection of hormonal messenger RNAs (mRNAs) in human pituitary adenomas. Positive signal for the appropriate mRNA was detected in tumours associated with Cushing's disease, acromegaly and hyperprolactinaemia, where immunoreactivity for adrenocorticotrophin (ACTH) growth hormone and prolactin had also been confirmed. In addition, we report the detection of proopiomelanocortin (POMC) mRNA in the rat pituitary gland using an oligodeoxynucleotide probe directly linked to alkaline phosphatase. PMID- 1923947 TI - In situ hybridization for different mRNA in GH-secreting and in inactive pituitary adenomas. AB - In a series of 40 pituitary adenomas in acromegaly all tumors showed mRNA for GH by in situ hybridization (ISH). The signals were mostly very strong and found in more than 80% of adenoma cells by using frozen sections. In paraffin sections the number of positive cells and the intensity of signals are lower. Prolactin mRNA was found in 87% of adenomas. In 27% more than 80% of cells were marked. beta HCGmRNA (with 90% hormology for LH-mRNA) was demonstrable in very sparse cells of 25% of adenomas. Comparing ISH with immunohistology (IH) we found a correlation between signals and hormone content in 100% of adenomas for GH, in 60% for Prolactin and in 10% for Gonadotropins. In 18% Prolactin mRNA but not the hormone was demonstrable and in 5% Prolactin was immunostained but no hybridization signals were detected. In a series of 40 clinically inactive adenomas sparse cells of three tumors expressed GHmRNA and two of these contained also the hormone, whereas in one adenoma GH but not GHmRNA was demonstrable. Prolactin mRNA was found in 8 adenomas. 7 of these also contained the hormone. In two cases Prolactin but not Prolactin mRNA was present. Beta-HCG(LH)mRNA and the respective hormones were shown in very sparse cells of 6 adenomas, whereas only beta-HCG(LH) mRNA was found in 8 cases. The significance of the findings is discussed. PMID- 1923948 TI - Quantitative in situ hybridization in neuro-endocrinology. AB - In situ hybridization has become one of the most powerful tools for localizing specific gene products in a tissue. Labelled molecular probes are used on tissue sections or on cells for localization of their hybridization sites. In situ hybridization makes it possible to define the spatial and temporal distribution of specific genes. The use of probes dually labelled, or the combined use of a molecular probe and labelled antibodies provides unprecedented opportunities to examine gene expression in individual cells. In addition, the quantification of gene products can shed light on regulation of gene expression at the cellular level. PMID- 1923949 TI - Mutations in the alpha subunit of the stimulatory regulatory protein of adenylyl cyclase (Gs) in human GH-secreting pituitary adenomas. Biochemical, clinical, and morphological aspects. AB - Very recently a subset of human GH-secreting pituitary adenomas carrying a somatic mutation in the alpha subunit of the stimulatory regulatory protein of adenylyl cyclase (Gs) was identified. In all these tumors (Group 2; about 30% of all the GH secreting tumors studied) the alpha s cDNAs contained mutations; in 8 tumors mutations replaced Arginine 201 with either Cystein or Histidine while in the remaining tumors Glutamine 227 was replaced by either Arginine or Leucine. No mutations were observed in the remaining adenomas (Group 1). The two mutations caused a constitutive activation of adenylyl cyclase and a turn on of cAMP synthesis by inhibiting GTPase activity. The transformed phenotype was reflected in adenomatous cells with high rate of cAMP production and in vitro GH secretion. No difference in age, sex, clinical features, duration of the disease and cure rate were observed between the patients without (Group 1) or with alpha s mutation (Group 2), while higher serum GH levels and smaller tumor size were present in Group 2 patients. Moreover, hypersecretory activity in Group 2 tumors was also apparent at electron microscopy; cells of Group 2 tumors were densely granulated and showed prominent rough endoplasmic reticulum and Golgi complex. With respect to Group 1, Group 2 patients were less responsive to GH-releasing hormone (GHRH), while they were more sensitive to somastostatin. The former finding is in agreement with the hypothesis that the oncogenic proteins mimic the effects of extracellular growth factors, so removing the requirement for GHRH; the latter might explain the low rate of tumor growth as due to the counteracting role of endogenous inhibitory factors. PMID- 1923950 TI - The pathology of clinically non-functioning pituitary adenomas. PMID- 1923952 TI - Neuropeptides of anterior pituitary origin. Autocrine or paracrine functions? AB - Several neuropeptides classically associated with the hypothalamus have been found in the anterior pituitary. The question arises whether they are locally synthesized and if they play a paracrine or autocrine role on pituitary cell functions. Using normal and tumoral human pituitaries we found neuropeptides (TRH, SRIH, GHRH) and dopamine in variable quantities according to the nature of the tissue. They were all present in normal pituitaries, while stimulatory hormones (TRH and GHRH) were predominantly found in tumoral tissue, implying an imbalance of pathophysiological importance between the stimulatory and inhibitory control of hypophyseal hormones (PRL and GH) in pituitary adenomas. Both normal and tumoral pituitaries released TRH, SRIH and GHRH in large amounts suggesting their local synthesis. The in situ synthesis was demonstrated for SRIH by the evidence of SRIH mRNA, the detection of SRIH immunoreactivity in peculiar cells and the presence of SRIH precursor. The possible role of these pituitary neuropeptides was suggested for instance by the negative correlation found in vitro between SRIH and GH secretions. Moreover, neuropeptides could interact with each other. Indeed DA stimulated TRH release while PRL secretion decrease at the same time. Pulses of TRH had differential effects on SRIH release according to the nature of the tissue as TRH inhibited SRIH release from adenoma while it stimulated SRIH release from normal pituitary. Concerning the effects of SRIH and GHRH on GH secretion, there was an endogenous regulatory pattern comparable to that observed in rat portal blood vessels. Pulses of GHRH induced GH secretion only when endogenous SRIH release was not stimulated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1923951 TI - Plurihormonal adenomas. Analysis of 62 cases. AB - This paper deals with the cytological features of pituitary plurihormonal adenomas based on 62 cases examined by histology, immunohistochemistry, ultrastructural study and post-embedding immunogold electron microscopy, including double labeling. In GH-cell containing adenomas, there were 9 adenomas consisting of exclusively GH and PRL cells. The other 39 adenomas contained other hormones as well as GH and PRL. Other nine combinations of pituitary hormones or alpha-subunit were observed. Special emphasis was laid on the fact that a greater part of GH-producing adenomas (74% by immunostain) were PRL-producing, although the ratio of GH-cells to PRL-cells widely varied from case to case. Concerning the double labeling study on mixed GH-PRL secreting adenomas, we recognized the existence of secretory granules containing GH only, those containing PRL only, those containing both GH and PRL and those containing neither. PMID- 1923953 TI - The role of hypothalamic hormones in the pathogenesis of pituitary adenomas. AB - There is evidence that hypothalamic hormones can regulate hormone secretion by pituitary adenomas. Hormone release by adenomas can be stimulated by hypothalamic releasing peptides; several hypothalamic inhibitory hormones or their analogues are used in the therapy of pituitary tumors to suppress hormone secretion and, in some cases, to reduce tumor size. A role for hypothalamic hormones in the development and growth of pituitary tumors has also been suggested by the association of pituitary adenomas with tumors producing hypothalamic hormones. In particular, tumors producing growth hormone-releasing hormone (GRH) or corticotropin-releasing hormone (CRH) have been associated with hyperplasia of their target adenohypophysial cells; a few have had pituitary neoplasms. Investigations have shown that some adenohypophysial cells respond to sustained stimulation by hypothalamic peptides with cell proliferation, however, it was not proven that the sustained stimulation resulted in the development of tumors. Recently, an animal model of disease was provided by mice transgenic for GRH. At 8 months of age, the mice developed pituitary mammosomatotroph hyperplasia; mice older than 12 months developed pituitary mammosomatotroph adenoma. It is suggested that continued hormonal stimulation plays a role in tumorigenesis, probably by promotion of cell replication. PMID- 1923954 TI - Effects of estrogens on pituitary cell and pituitary tumor growth. AB - Estrogens have been known to induce PRL cell hyperplasia in the anterior pituitary of some species for many decades. Recent studies have shown variable susceptibility to estrogen-induced hyperplasia in different strains of rats. The distinction between hyperplastic pituitaries and adenomas is usually not made by most investigators in this field, although true neoplasms can usually be propagated by serial transplantation. The growth of transplantable tumors is usually inhibited by estrogen in vivo. Estrogens have a biphasic effect on pituitary cell proliferation in vitro with higher concentrations of estradiol inhibit cell growth, and lower concentrations stimulating PRL secretion. Estrogens can regulate PRL gene methylation in vivo thus affecting PRL mRNA expression. Recent studies have suggested that estrogen regulates signal transduction by stimulating protein kinase C. Estrogens also regulate specific proto-oncogenes such as c-myc and c-fos. These observations may help to explain some of the regulatory effects of estrogens on cell proliferation and tumor development. PMID- 1923955 TI - Surgical outcome and pathological effects of bromocriptine preoperative treatment in prolactinomas. AB - The case histories of 40 patients with prolactinomas were retrospectively reviewed. Twenty patients treated preoperatively with bromocriptine were compared to 20 untreated patients. The two groups were comparable according to tumor size and sex. All the patients had an immuno-cytochemically confirmed prolactin adenoma. They were operated on by a transsphenoidal approach. Intraoperative findings were studied. The surgical cure rates (serum PRL level less than 30 micrograms/l) of the bromocriptine-treated group were higher than those of the control group, both in microprolactinomas (87.5% vs 50%) and macroprolactinomas (33% vs 17%). This improvement of surgical success rate may not be due solely to bromocriptine. Surgical cure also depends on preoperative serum PRL levels (less than 500 micrograms/l) and tumoral size (less than grade II0). Tumoral tissue remained in all cases. No increase in fibrosis was observed. By inducing tumoral shrinkage, bromocriptine makes surgical removal of macroprolactinomas easier and safer. This tumoral shrinkage could be explained not only by reduction of cell size, but also by decrease in intratumoral hemorrhage. Preoperative bromocriptine treatment does not adversely affect surgical outcome. Moreover, it may be useful in cases of macroprolactinomas with suprasellar extension. PMID- 1923957 TI - Cushing's disease: a correlation of radiological, surgical and pathological findings with therapeutic results. AB - From 1963 to 1990 78 successive patients with pituitary-dependent cortisol hypersecretion were submitted to transsphenoidal surgery. In 57 patients, a selective adenomectomy was performed. Sixteen other patients had a central hypophysectomy. Total hypophysectomy was done nine times: in five new patients and in four patients previously operated by us. Fifty-six tumors were studied in pathology. Fifty tumors were microadenomas with ten of these measuring less than 1 mm. The tumors consisted of basophilic cells giving a positive immunostaining for ACTH. Electron microscopy on 35 tumors was characteristic with perinuclear bundles of microfilaments and often large lipid vacuoles. We did not find ACTH cell hyperplasia in the pituitary gland around tumors or in specimens of central or total hypophysectomy. Adequate follow-up was obtained on 49 patients who had been cured with an average length of 6.4 years after surgery. Our longest sustained remission following selective adenomectomy is eighteen years. Surgical cure rate was 82% for microadenomas and 81% for all intrasellar tumors. 89% of patients went into remission after total hypophysectomy but only 56% when central hypophysectomy was performed. Recurrence rate was 7.6%, occurring between three and seven years after surgery. PMID- 1923956 TI - Effects of bromocriptine on experimental GH3 cell tumors. AB - Bromocriptine in concentrations up to 10(-4) M was studied for morphological and endocrinological effects upon the GH3 cell line as well as the GH1 and AtT-20 cell lines. The cells (10(5)/ml) were incubated with RPMI 1640 or in some experiments Dulbecco's Modified Eagle's Medium supplemented with 10% FCS. Bromocriptine was added in concentrations of 10(-4) to 10(-8) mol/L and aliquots of medium were obtained at 2 and 24 hs for the determination of growth hormone and prolactin. Significant reductions in concentrations of growth hormone and prolactin as well as cell number were observed with a concentration of bromocriptine of 10(-4) M at 24 hs. The electron microscopic appearance of GH3 cells treated with 10(-4) mol/L concentrations of bromocriptine for 24 hs demonstrated extensive and marked vacuolization in the cytoplasm which had already appeared 2 hs after treatment with bromocriptine. In bromocriptine treated (10(-4) mol/L for 24 hs) GH1 cells and AtT-20 cells, the morphologic features were essentially unchanged, compared to the untreated group. Since many previous reports demonstrated a defective dopamine receptor system in GH3 cells, it must be concluded that bromocriptine has an extradopaminergic action which is selectively observed in GH3 cell. PMID- 1923958 TI - Lectin-bindings in pituitary adenomas and normal pituitaries. AB - The first study was undertaken for detecting hormone-receptors for estrogen and progesteron with immunohistochemical methods in frozen sections of 58 pituitary adenomas of different types. In all cases the result was negative. In the second study we tested the binding pattern for the lectins Peanut lectin (PNA), Ulex europaeus agglutinin (UEA-1) and the Concanavalin agglutinin (Con-A) in 144 pituitary adenomas of different types and in 20 post-mortem pituitaries using the two-layer indirect technique. All normal pituitaries reacted positive for all three lectins, elsewhere the binding feature for pituitary adenomas was different. Via statistical analysis, correlating lectin-bindings with clinical hyperfunction and immunohistochemical hormone content, we found an association of acromegaly and PNA and ConA and of Cushing's disease and PNA and UEA-1; furthermore of GH and UEA-1 and Con-A, of TSH and UEA-1 and of ACTH and PNA and UEA-1. Using serial sections (AB-method for demonstrating hormones and two layer indirect technique for lectin-binding) and the double-staining technique (labelled Streptavidin-Biotin-method for demonstration of hormones and the two layer indirect technique for lectins) we found Con-A reacting with GH and PRL cells and with a part of FSH-cells, UEA-1 reacting with most of the ACTH-cells and PNA reacting with FSH-cells. PMID- 1923959 TI - Invasiveness of pituitary adenomas. AB - 528 biopsies from 396 pituitary adenomas were re-examined by light microscopy and checked for invasion of neighbouring tissues. The overall invasion rate was 41.9%. Highly differentiated ACTH-cell adenomas were invasive in 24.1%, undifferentiated mucoid-cell adenomas in 66.7%. The histological type of invasion was influenced by the adenoma type and by the invaded tissue. There was no obvious correlation between the adenoma type and the invaded tissue. PMID- 1923960 TI - Transurethral microwave hyperthermia: an alternative treatment for prostadynia? AB - A total of 15 patients with severe symptoms of prostadynia who were refractory to therapy were treated with transurethral microwave hyperthermia (TUHT) in a phase I trial. All patients had pain as the predominant symptom, 9 (60%) patients gave a history of psychological problems while frequency, urgency, dysuria, nocturia, and impotence were less common symptoms. Treatment consisted of TUHT at 915 MHz given weekly for 5 weeks with a total of 68 treatment sessions and a mean of 4.5 treatments per patient. Each treatment lasted for 60 minutes. The aim was to increase the temperature measured on the urethral surface to greater than or equal to 44 degrees C. T mean for all sessions was 45.5 degrees C. In 91% of treatments, the temperature was greater than or equal to 44 degrees C. Treatment was well tolerated in 87% patients and acute toxicity was mild. Of the 15 patients treated, 2 (13%) did not complete the treatment course due to discomfort during TUHT. Good treatment response, manifested by complete pain relief and a decrease in dysuria, was noted in 7 (47%) patients. A higher (greater than or equal to 46 degrees C) treatment temperature correlated well with good response, P less than .01. Similarly, relief of pain correlated well with the absence of a history of psychological problems, P less than .01. A decrease of obstructive micturition problems was noted in 5 of the 7 patients who had this upon presentation. This study showed evidence of therapeutic activity with the use of TUHT in patients with prostadynia refractory to therapy. The response obtained was limited to less than one-half of the patients. Complete pain relief was obtained in 4 (27%) patients. It is of interest to note that patients who had major benefit did not show evidence of psychological problems and were able to tolerate higher treatment temperatures. The latter could suggest a temperature related response. PMID- 1923961 TI - Bladder exstrophy-epispadias complex: prostatic evaluation by transrectal ultrasonography. AB - Seven patients with bladder-exstrophy-epispadias complex underwent high resolution prostatic ultrasonography in order to establish the presence and appearance of their prostate gland and seminal vesicles. Six patients had been born with classic bladder exstrophy, and one patient with complete epispadias. The size of the prostate gland was in the normal range in three patients. Three patients had small glands, and in one patient no prostatic tissue could be identified. Two patients showed an unusual position or echoappearance of their glands. The seminal vesicles in five patients were relatively large, contained multiple cystic spaces, and/or extended posteriorly and inferiorly to the prostate gland proper. Our study demonstrates that the prostate gland and seminal vesicles are present in patients with bladder exstrophy. The unusual appearance, position, and size in most patients, however, suggests faulty embryologic development or changes secondary to surgery reflecting the complex nature of the condition. Likewise, the enlarged seminal vesicles may indicate impaired drainage of these structures secondary to the initial bladder closure or subsequent bladder neck reconstruction. PMID- 1923962 TI - Effect of etidronate disodium on the development of bone lesions in an animal model of bone metastasis using the human prostate cancer cell line PC-3. AB - We have established an animal model of bone metastasis using the PC-3 human prostate tumor cell line. In order to assess whether inhibition of bone resorption would prevent the development of bone metastasis, the diphosphonate etidronate (EHDP) was administered to 20 mice at a dose of 30 mg/kg subcutaneously daily starting 2 days prior to injection of tumor cells. Control mice received daily injections of the saline vehicle. In the EHDP-treated mice, there was no significant reduction in the incidence of bone metastasis, the size of the lesions, or the number of bone lesions per mouse. Approximately 50% of the mice developed bone metastasis, which was similar to the control group and similar to what was observed in earlier studies with this animal model. Histomorphometric analysis of bones showed marked inhibition of mineralization in EHDP-treated mice, thus indicating biological effect on the bone. Therefore, the use of EHDP in biologically effective doses failed to reduce the incidence, size, or number of bone metastases in this animal model. PMID- 1923963 TI - Glycoconjugates of the lateral prostate of the guinea pig: a lectin histochemical study. AB - The present study examined the glycoconjugates of the lateral prostate using a battery of lectins. The results indicated that the secretory epithelium was rich in mannose (Man), N-acetylglucosamine (GlcNAc), galactose (Gal), N acetylgalactosamine (GalNAc), and complex oligosaccharides. Con A (concanavalin A), LCA (Lens culinaris agglutinin), PSA (Pisum sativum agglutinin), WGA (wheat germ agglutinin), PWM (pokeweed mitogen), RCA-I (Racinus communis isolectin I), and PHA-P (Phaseolus vulgaris agglutinin-P) reacted intensely with both epithelia and stroma, while SBA (soybean agglutinin) and PNA (peanut agglutinin), which bind to terminal Gal, GalNAc, and Gal beta 1,3 GalNAc appeared to be specific to the secretory epithelium. SBA and PNA were useful as markers in the study of the secretory function of the prostate gland. The present study has shown that the Golgi apparatus of prostatic epithelial cells was rich in fucose (Fuc), oligomers of GlcNAc, Gal beta 1,3 GalNAc, Gal, and Man containing glycoconjugates, indicating that the gland was actively involved in glycosylation. The present study has also shown that LTA (Lotus tetragonolobus agglutinin) is a good marker for the epithelial Golgi. PNA also bound to the epithelial basement membrane and the connective tissue in the lamina propria. The present study has thus established, for the first time, the glycoconjugate patterns in the lateral prostate of the guinea pig. PMID- 1923964 TI - Autocrine regulation of DU145 human prostate cancer cell growth by epidermal growth factor-related polypeptides. AB - The DU145 human prostate cancer cell line possesses epidermal growth factor (EGF) receptors and synthesizes both EGF and the related polypeptide transforming growth factor-alpha (TGF-alpha). A monoclonal antibody to the EGF receptor was used to determine whether these characteristics were indicative of a functional autocrine regulatory system. This antibody competed effectively with [125I]EGF for binding to DU145 cell binding sites over a 1 x 10(-11) to 1 x 10(-7) M concentration range, and did so with a capability similar to that of the two natural ligands. It inhibited growth of these cells in both 3% fetal bovine serum supplemented and serum-free medium; in experiments with incubation times of 3-5 days there was a 45-50% reduction in cell number. Growth suppression by the EGF receptor blockade of cells plated at a density of 1.5 x 10(4) cells/ml/well was reversed competitively by the addition of EGF to the medium; 0.3 nM completely eliminated the inhibitory effect of a 1 x 10(-9) M antibody concentration. It is concluded that DU145 cell growth is regulated by an EGF-mediated autocrine loop. PMID- 1923965 TI - Suppressive antibiotic therapy in chronic prosthetic joint infections. AB - Thirteen patients with chronic total joint infections (eight knees, five hips) were treated with suppressive antibiotic therapy and retention of the prosthesis following surgical debridement and 4 to 6 weeks of intravenous antibiotic therapy. These patients faced poor functional outcome after prosthesis removal. After a mean follow up of 37.6 months (range: 24 to 55), only three patients have retained their prostheses. Ten patients required prosthesis removal for recurrent infection a mean of 21.6 months (range: 6 to 48) after starting suppressive therapy. In addition, 38% of patients experienced adverse effects which led to changes in the antibiotic regimen. Suppressive antibiotic therapy in the treatment of chronic prosthesis infections has limited clinical efficacy and is associated with a substantial risk of adverse effects. PMID- 1923967 TI - Percutaneous computed tomography stabilization of moderate to severe slipped capital femoral epiphysis. AB - A percutaneous computed tomography (CT) guided pinning of experimentally reproduced slipped capital femoral epiphysis in five cadavers and one patient- who had bilateral pinning for moderate and severe grade chronic slip--was conducted. Prior investigations of cadavers revealed that this procedure can be performed in selected cases. The details of the technique are illustrated in this article. PMID- 1923966 TI - Rigid internal fixation for shoulder arthrodesis. AB - Fifteen patients underwent a shoulder arthrodesis utilizing standard dynamic compression plate fixation, but with limited postoperative immobilization with only an abduction pillow. In each case, the position of the extremity relative to the scapula and trunk was recorded immediately postoperatively, at regular intervals until fusion, and at follow-up evaluations. Thirteen of 15 shoulders fused without change of intraoperative position after an average postoperative period of 4 months. One patient lost position in the early postoperative period secondary to inadequate fixation, but subsequently fused. Another who demonstrated a persistent non-union at 2 1/2 years was subsequently explored and underwent a bone graft. Four patients complained of residual symptomatic hardware, with two requiring surgical removal of the plate and screws. All but one patient were satisfied with the clinical result at follow up. Only two patients were within 5 degrees of the preoperatively determined position of 30 degrees abduction, 30 degrees forward flexion, and 30 degrees internal rotation. However, almost all were able to function satisfactorily. The authors concluded that shoulder arthrodesis utilizing rigid internal fixation without postoperative cast or brace immobilization maximizes patient comfort without compromising the success of arthrodesis. However, control of arm position remains inexact and additional modifications are needed to ensure fusion position and to minimize disability. PMID- 1923968 TI - Stress fractures of the anterior tibial diaphysis. AB - Stress fracture of the anterior tibial diaphysis is rare and occurs mostly in leaping athletes. Thirty-six of these fractures in 35 patients have been reported in the literature. These are combined with 15 similar fractures in our experience to provide combined data on 51 anterior tibial stress fractures. Comparison of the various treatments utilized disclosed that there is a high risk of complete fracture if affected patients are allowed full activity, and that treatment by rest alone allowed only 40% to return to full activity even after symptomatic improvement. The treatment recommended for these patients is excision of the fissure, transverse drilling at the fissure site, and cancellous bone grafting of the defect. In those patients who suffer a complete fracture, open reduction and internal fixation is superior to closed treatment. PMID- 1923969 TI - Integrating computers into orthopedic research. AB - The role of computers in orthopedic research and education is expanding rapidly. Its potential to manipulate large amounts of data and execute multiple complex assignments with great speed and accuracy indeed make the computer an awe inspiring device. An important instrument in research is the computerized database, a collection of related data arranged so that useful information may be retrieved. Computer models derived from classical physics and fluid mechanics have been used to study motion of both extremities and spinal articulations. Computers also have found usefulness in clinical orthopedic research. The orthopedist of the future will use the computer directly in clinics and private practice for patient evaluation, computer-assisted preoperative planning, and financial recordkeeping. PMID- 1923970 TI - A hyperextension injury of the thoracic spine in association with diffuse idiopathic skeletal hyperostosis. PMID- 1923971 TI - Osteosclerotic IgA myeloma: a case involving a rare variant (the POEMS syndrome). PMID- 1923972 TI - Perthes'-like changes caused by acquired hypothyroidism. PMID- 1923973 TI - Crossed pins vs parallel pins in the treatment of femoral neck fractures. AB - Twenty femoral neck fractures treated with three crossed modified Knowles pins (Gouffon pins) were compared to 20 fractures treated with three parallel pins. All patients had survived for more than 2 years after operation. The groups were comparable concerning Garden stage, reduction, and age. No significant difference concerning the failure rate was found. PMID- 1923975 TI - Radiologic case study. Spontaneous osteonecrosis of the knee. PMID- 1923974 TI - Closed unstable fractures of the tibial and fibular shafts at the same level. PMID- 1923976 TI - Localization of eosinophil granule major basic protein in incontinentia pigmenti. AB - We report a case of incontinentia pigmenti and demonstrate the deposition and localization of eosinophil major basic protein (MBP) in the vesicular stage of this neurocutaneous syndrome. The initial stage of incontinentia pigmenti is histologically characterized by intraepidermal vesicles associated with eosinophilic spongiotic dermatitis. Pathologic examination of a lesional tissue specimen from our patient demonstrated epidermal necrosis, spongiosis, and vesicle formation. Indirect immunofluorescence with affinity-chromatography purified antibody to human eosinophil granule MBP demonstrated many intact eosinophils within vesicles and scattered throughout the epidermis and dermis, and extracellular deposition of granular MBP in the tissue. The characteristic finding of extensive tissue eosinophilia in incontinentia pigmenti, as well as the new finding of extracellular deposition of an eosinophil granule protein in lesional tissue, suggests the involvement of eosinophils in the pathogenesis of the disease. PMID- 1923977 TI - Obsessive-compulsive disorders in the pediatric dermatology practice. AB - Childhood and adolescent obsessive-compulsive disorders are sometimes seen in dermatology practice. When present, OCD is most frequently manifested in younger patients as trichotillomania, onychotillomania, onychophagia, and acne excoriee. In addition to these disorders, obsessive hand washing, AIDS phobia, and other psychosomatic dermatoses characterized by obsessive-compulsive tendencies are seen in all age groups. It is important to define the nature of any underlying psychiatric disorder before beginning drug treatment of these patients. With the availability of new medications, most notably, clomipramine and fluoxetine, there is reason for optimism regarding the treatment of OCD. Whenever feasible, the dermatologist should not hesitate to involve a psychiatrist to help with diagnosis and treatment when the diagnosis of OCD is being considered. PMID- 1923978 TI - Evaluation of minor clinical features of atopic dermatitis. AB - The diagnostic significance of 19 previously proposed minor features of atopic dermatitis was evaluated. The frequency of these features was studied in 50 patients with typical atopic dermatitis compared to that in 50 control subjects. The ages of all individuals ranged from 3 months to 12 years. Six of the minor features, chelitis, nipple eczema, perifollicular accentuation, white dermographism, recurrent conjunctivitis, and anterior neck folds, were encountered as often in patients as in controls. Two additional features that were of diagnostic significance were diffuse scaling of the scalp and infraauricular fissuring. PMID- 1923979 TI - Keratoacanthoma arising in an organoid nevus during childhood: case report and literature review. AB - We report an 11-year-old girl with an organoid nevus of the cheek. She represents the first report of a keratoacanthoma arising within an organoid nevus in childhood. PMID- 1923980 TI - A lichen striatuslike eruption adopting the morphology of Blaschko lines. AB - A 15-month-old girl had orange papules that formed V-shaped lines on her back. The clinical evolution and histology were compatible with the diagnosis of a lichen striatus-like eruption, adopting a special morphology by following Blaschko lines. PMID- 1923981 TI - Infantile myofibromatosis. AB - Infantile myofibromatosis is part of a heterogeneous group of rare childhood fibromatoses characterized by the proliferation of myofibroblasts. It is not a common condition and is frequently misdiagnosed. We present an unusual patient who had small, depressed, atrophic, skin lesions uncharacteristic of infantile myofibromatosis. PMID- 1923982 TI - Kasabach-Merritt syndrome. AB - The Kasabach-Merritt syndrome includes the triad of vascular tumors, thrombocytopenia, and a hemorrhagic diathesis. The vascular tumors are usually benign but the associated coagulopathy may be life threatening. We describe a patient whose clinical course illustrates the potential difficulties in management. PMID- 1923983 TI - Benign neonatal hemangiomatosis with aggressive growth of cutaneous lesions. AB - A patient experienced rapidly proliferating, multiple cutaneous hemangiomas subject to significant hemorrhage, with associated asymptomatic pulmonary involvement. The dramatic features of his cutaneous disease, an overview of the spectrum of neonatal hemangiomatosis, and recent therapeutic options are reviewed. PMID- 1923985 TI - Xanthelasmoid mastocytosis. AB - An 8-year-old girl had small, papular vulval lesions for six years; the lesions were yellowish with numerous surface depressions. Symptoms due to the action of mastocyte mediators were observed. A biopsy specimen showed a dense monomorphous infiltrate of the deep dermis by rounded cells with granular cytoplasm and a round or oval central nucleus. The morphology of the lesions and red-purple metachromatic staining led to the diagnosis of xanthelasmoid mastocytosis. Symptoms were controlled with hydroxyzine. Annual follow-up has shown no evidence of systemic involvement to date. Surgery should be contemplated as a future therapeutic option, in view of the location of the lesions. PMID- 1923984 TI - Diffuse cutaneous mastocytosis mimicking staphylococcal scalded-skin syndrome: report of three cases. AB - Three cases of diffuse cutaneous mastocytosis (DCM) were at first incorrectly diagnosed as staphylococcal scalded-skin syndrome. In the first patient, at age 1 day the disease was recognized promptly by simple techniques such as Darier's sign and Tzanck smear. Much delay in making the diagnosis occurred in the other two patients, however: almost 1 year and 15 years, respectively. Bullous manifestations in mastocytosis occur only in the first two or three years. In the first months the disease can be dangerous and life threatening. To distinguish mastocytosis from vesicular and bullous neonatal disorders, one should perform Darier's sign and a Tzanck smear. The diagnosis is confirmed by histopathologic studies. Treatment of the bullous manifestations is symptomatic, with zinc oxide paste and oral antihistamines, which may provide some relief. In addition, cimetidine and sodium cromoglycate may be beneficial. At a later age psoralen plus ultraviolet A therapy may also relieve the symptoms. Particular foods and medicines can liberate histamine and should be restricted as much as possible in extremely affected patients. Special care should be taken when these patients are to undergo anesthesia. The risk of complications during and after anesthesia is also present in other forms of mastocytosis. PMID- 1923986 TI - Dry skin of newborn infants: functional analysis of the stratum corneum. AB - Our clinical observations disclosed that most newborn infants showed scaling on at least some parts of the body. To clarify the mechanism for such xerosis, we performed measurements of high-frequency conductance (Gx), which assesses the skin surface hydration and evaporative water loss from the skin. The skin of newborns showed surprisingly lower Gx values and evaporative water loss than those of adults or 1- to 6-month-old infants in a warm environment. These findings may be explained partly by low eccrine activity, which has been reported as characteristic of newborn skin. However, defective stratum corneum function, such as reduced water-holding capacity as demonstrated by the in vivo water sorption-desorption test, also seems to be responsible for the development of dry skin in newborns. PMID- 1923987 TI - Jacquet erosive diaper dermatitis in a young girl with urinary incontinence. AB - We report a case of Jacquet erosive diaper dermatitis (dermatitis syphiloides posterosiva) in a 9-year-old girl suffering from urinary incontinence due to an ectopic opening of a left double ureter into the vaginal vestibule. The toilet paper that she used as an absorbent was thought to be one of the factors causing the eruption. The lesions cleared with topical application of a nonsteroidal antiinflammatory ointment and zinc oxide ointment, in conjunction with the use of sanitary napkins. PMID- 1923988 TI - Treatment of the poikilodermatous component of the Rothmund-Thomson syndrome with the flashlamp-pumped pulsed dye laser: a case report. AB - The Rothmund-Thomson syndrome is a rare disorder characterized by poikiloderma, juvenile cataracts, bone abnormalities, short stature, sparse hair, hypogonadism, defective dentition, nail dystrophy, hyperkeratosis, and mental retardation. A 12 year-old boy with the syndrome was referred to us for evaluation and treatment of poikiloderma. This component of the disease was markedly improved with the use of pulsed dye laser photocoagulation. PMID- 1923989 TI - Acral hemorrhagic eruption in a 3-year-old boy. PMID- 1923990 TI - Congenital localized absence of skin associated with dystrophic epidermolysis bullosa. PMID- 1923991 TI - Lichen sclerosus et atrophicus in children and young adults. AB - We performed a retrospective study of 52 children and young adults (average age 18 yrs) with lichen sclerosus et atrophicus. In 56% of patients the eruption was still present after a follow-up of 7.5 years. Younger patients were most likely to show improvement. The histologic appearance of both groups (patients with persistent lesions and those with resolution of lesions) showed classic features of lichen sclerosus et atrophicus: homogenized collagen with an underlying bandlike lymphocytic infiltrate. Epidermal changes such as atrophy, hyperplasia, and follicular plugging were slightly more prominent in patients with persistent lesions. Menarche, pregnancy, and the presence of extragenital lesions had no effect on the prognosis, but since the condition resolved, on average, during adolescence, unknown developmental factors may be implicated. PMID- 1923992 TI - [Involutional osteoporosis--pathogenesis, diagnosis, prevention and therapy]. PMID- 1923993 TI - [Plasminogen activator inhibitors from neoplastic tissues]. AB - This article contains a survey of works, published in the last few years on plasminogen activators inhibitors in neoplastic tissues. These inhibitors belong to a heterogenous group of proteins, having different molecular weights and specific ways of acting. They exemplify immunological relationship to known inhibitors of fibrinolysis from normal tissues--i.e. the inhibitors from endothelial cells--(PAI-1) and placental inhibitor--(PAI-2). To PAI-1 type belong: acid-stabile inhibitor of fibrinolysis with Mr 50,000 from HTC hepatoma cells in rats, acid-labile inhibitor Mr 42,770 produced by HepG2 human hepatoma cells; the inhibitor with Mr 54,000 from HT 1080 human cells from fibrosarcoma and single-chain acid-stabile inhibitor with Mr 50,000 from MJZJ melanoma cells. In PAI-2 type we can mention the inhibitor with Mr 47,000 from U-937 histiocytic lymphoma cells. PMID- 1923994 TI - [Cellular and plasma carboxypeptidases]. AB - The literature on carboxypeptidases of cells and plasma is reviewed. Subcellular localization, physico-chemical properties, chemical structure and biological significance of these enzymes are discussed. PMID- 1923995 TI - [Interleukins 4 and 5--factors regulating the activity of the immune system]. PMID- 1923996 TI - [Immunophenotypic characteristics of the epithelial cells of ovarian neoplasms]. AB - Paper presents the progress in antigenic characterization of different histological types of ovarian carcinomas. The role of monoclonal antibodies is pointed out. Clinical significance of tumor-associated antigens and problems of tumor cell heterogeneity for immunological studies are also reviewed. PMID- 1923997 TI - [Hormonal medium of the fetus]. PMID- 1923998 TI - Managing chronic hepatitis. Recent advances in diagnosis and treatment. AB - A variety of effective therapies are now available for chronic hepatitis of various causes. Most patients with autoimmune chronic active hepatitis respond to immunosuppressive therapy, and those with Wilson's disease respond to copper chelating therapy. Patients with drug-induced chronic hepatitis improve with cessation of the medication. About 30% to 40% of patients with chronic hepatitis B infection respond to interferon alfa, as do about 50% of those with chronic hepatitis C infection. PMID- 1923999 TI - An aspirin a day. PMID- 1924000 TI - Gallstone symptoms. Myth and reality. AB - Gallstones are very common, but at least two thirds of detected stones are asymptomatic and a large number undoubtedly go undetected. The presence of symptoms or complications is the indication for surgery. It is important to accurately identify which symptoms are caused by gallstones, because removing the gallbladder will relieve only these symptoms. Making this determination is a challenge, however, because the classic picture of biliary colic may be inaccurate and the connection between gallstone disease and flatulent dyspepsia is questionable at best. Descriptions of both these conditions are based on anecdotal evidence or reports of uncontrolled surgical series. A review of recent controlled trials suggests that the pain of biliary colic is constant and infrequent, comes in episodes lasting 1 to 5 hours, is located in the epigastrium or right upper quadrant of the abdomen, and characteristically occurs at night. There are few additional symptoms other than nausea or vomiting, and colic is not induced by eating fatty meals. Flatulent dyspepsia--a symptom complex of vague pain in the right upper quadrant, fatty-food intolerance, and bloating--is probably not related to the presence of gallstones in the majority of patients. PMID- 1924001 TI - Extreme hyperkalemia induced by drugs. AB - Because of age and disease-induced pathophysiologic changes, elderly and diabetic patients are prone to hyperkalemia under even the best of circumstances. Further complicating the situation is the fact that the drugs often prescribed for these populations can affect potassium homeostasis. Drs Rigolin and Chap describe a case in which an elderly diabetic man with azotemia survived extreme drug-induced hyperkalemia. PMID- 1924002 TI - Guillain-Barre syndrome. An uncommon but severe illness. AB - It is important for primary care physicians to be familiar with Guillain-Barre syndrome, a relatively rare disorder that may occur after another illness or after stress such as surgery. Although most patients recover fully, respiratory failure and cardiovascular failure are possible complications. Rapid diagnosis and referral to specialists experienced in plasmapheresis therapy can significantly benefit patients. PMID- 1924003 TI - Medical school is too expensive! PMID- 1924004 TI - Clostridium septicum infection. Beware of associated cancer. AB - For reasons that are not fully understood, there is an association between Clostridium septicum infection and carcinoma. In this article, Dr Kirchner describes the examination and treatment of a patient with C septicum infection in whom metastatic cancer was found on laparotomy. PMID- 1924005 TI - Neurologic complications of alcoholism. AB - The neurologic effects of alcohol on physical and mental function vary in severity and reversibility. When primary care physicians recognize and treat these conditions, recovery from alcoholism is made easier for patients and their families. Dr Lehman summarizes the central nervous system effects of alcohol abuse and makes recommendations for diagnosis and treatment during both acute intoxication and withdrawal. PMID- 1924006 TI - Diagnosing syncope. With an emphasis on cardiac causes. AB - Evaluation of syncope may be lengthy and expensive, and, in up to 50% of patients, will not produce a diagnosis. If a definite cause is found, specific therapy may offer symptomatic relief, although the patient's prognosis depends primarily on the nature and severity of any underlying disease. A patient with no evidence of organic heart disease for whom a complete evaluation reveals no cause for syncope has an excellent prognosis, even though syncopal symptoms may recur. The initial evaluation and management of most patients with syncope can be performed by the primary care physician if facilities for Holter monitoring, echocardiography, and signal-averaged electrocardiography are available. Consultation with a cardiologist is necessary only when the results of the initial evaluation are unrevealing or if findings suggest the need for a more intensive secondary elevation. PMID- 1924007 TI - Hypertrophic cardiomyopathy. Why is it often overlooked in elderly patients? AB - The lack of awareness that hypertrophic cardiomyopathy is indeed seen in older patients is widespread. The resulting low index of suspicion, coupled with the fact that the clinical presentation of this condition closely resembles the presentations of several common disorders of the elderly, can lead to misdiagnosis and inappropriate and possibly harmful treatment. When an elderly patient presents with dyspnea, angina, or syncope, the presence of a systolic murmur that changes in intensity with appropriate diagnostic maneuvers should prompt consideration of hypertrophic cardiomyopathy, which can be easily verified (or excluded) by echocardiography. This approach minimizes diagnostic and therapeutic errors. PMID- 1924009 TI - Hyperlipidemia. What to do when life-style changes aren't enough. AB - Most lipid abnormalities seen in a primary care practice can be grouped into three categories: hypercholesterolemia, combined hyperlipidemia, and hypertriglyceridemia. Three to 6 months of dietary and life-style alterations should be tried before drug treatment is initiated. Drugs for each category should be chosen on the basis of clinical efficacy, established long-term safety, and effects on low-density and high-density lipoprotein cholesterol and triglyceride levels. To maximize compliance, physicians should advise patients on dosing schedules, side effects, and required monitoring. Combination drug therapy is often necessary to reach treatment goals, especially in patients with genetic hyperlipidemia and/or symptomatic coronary artery disease. PMID- 1924008 TI - Hypertriglyceridemia. Examining its role in coronary heart disease. AB - If triglyceride-rich very-low-density lipoproteins (VLDLs) are a vehicle for transporting cholesterol into the arterial wall, they can be equated to low density lipoproteins (LDLs) in estimating CHD risk and setting targets for therapy. Furthermore, the fate of cholesterol-rich VLDL (VLDL remnants) is similar to that of LDL; that is, both are removed from the circulation via LDL receptors. Thus, combining VLDL and LDL into a common category of atherogenic lipoproteins provides a rational framework for treatment of hypercholesterolemic patients with hypertriglyceridemia. A hydroxymethylglutaryl coenzyme A reductase inhibitor may be the best choice for treatment when both triglyceride and cholesterol levels are elevated, because these agents cause the greatest reduction in VLDL and LDL cholesterol levels. When hypertriglyceridemia is severe, a fibric acid or nicotinic acid is preferable, because these agents are more effective for lowering triglyceride levels and hence for reducing risk for acute pancreatitis. PMID- 1924010 TI - Aspirin sensitivity. A distressing reaction that is now often treatable. AB - Aspirin-induced hypersensitivity affects a substantial number of people, including 20% or more of asthmatic patients. A dramatic flare of symptoms occurs after indigestion of aspirin or a nonsteroidal anti-inflammatory drug, and symptoms can persist even after the agent is discontinued. Fortunately, aspirin desensitization, as described by the authors, now appears to be a treatment option. PMID- 1924011 TI - Osteoarthritis and rheumatoid arthritis in elderly patients. Differentiation and treatment. AB - Osteoarthritis is differentiated from rheumatoid arthritis by age at onset, duration of morning stiffness, pattern of joint involvement, and radiographic findings. Distinguishing between the diseases can be challenging, because they have some symptoms in common. Therapy for osteoarthritis is aimed at relief of symptoms; treatment of active rheumatoid arthritis is more aggressive, aimed at controlling or modifying the disease. Both diseases may cause great pain and disability in elderly patients, so prompt diagnosis and treatment are essential. PMID- 1924012 TI - An awakening. PMID- 1924014 TI - Advice about pool safety. PMID- 1924013 TI - When does acetaminophen poisoning require treatment? PMID- 1924015 TI - Enalapril maleate and teprotide. PMID- 1924016 TI - Pneumonia. Pearls for interpreting patients' radiographs. AB - The chest radiograph can detect pneumonia, but laboratory evaluation is needed to determine the specific causative organism. However, before these results become available, a presumptive diagnosis can be made with the help of chest radiography. A lobar pattern on radiography is usually produced by pneumococcal and Klebsiella infections. A lobular (bronchopneumonia) pattern may be produced by Staphylococcus, gram-negative organisms, and anaerobes. An interstitial pattern results from viral, Mycoplasma, and Pneumocystis carinii infections. Mixed patterns may also occur. There is great variation in the presentation of each infection. However, pertinent clinical information, epidemiologic factors, and associated radiographic findings (eg, adenopathy, pleural effusion, cavitation) are helpful in further limiting diagnostic possibilities. PMID- 1924017 TI - Pneumonia and chronic obstructive pulmonary disease. What special considerations does this combination require? AB - Patients with chronic obstructive pulmonary disease are at increased risk for both community- and hospital-acquired pneumonia, most often through aspiration. Community-acquired pneumonia often manifests with acute onset of chills, fever, cough, and pleuritic chest pain. Atypical pneumonia syndromes are characterized by subacute onset over several days and constitutional complaints. Hospital acquired pneumonia may be contracted during altered consciousness or after intubation, ventilation, or exposure to pathogens. Knowledge of the disease process and the means to accurately diagnose these infections allows physicians to prescribe effective antibiotic therapy. Stable patients may receive oral therapy, but with severe or hospital-acquired pneumonia, parenteral therapy is required. Combinations of agents may be needed to cover the variety of pathogens that may be present. PMID- 1924018 TI - Atypical pneumonias. Clinical diagnosis and empirical treatment. AB - Atypical pathogens play an important role in the pathogenesis of community acquired pneumonias. Early definitive diagnosis is often difficult. Careful attention must be given to the patient's history and other diagnostic clues. When a specific pathogen seems very likely to be the cause, appropriate and cost effective empirical therapy is best accomplished with a single-drug regimen. However, when typical and atypical pathogens are suspected, combination drug therapy is preferred until the diagnosis is firm and one of the two antibiotics can be dropped. PMID- 1924019 TI - Immunopathology of Behcet's disease. PMID- 1924020 TI - Management of carcinoid syndrome. PMID- 1924022 TI - Marfan syndrome affecting four generations of a family without ocular involvement. AB - Thirty eight relatives of a patient with Marfan syndrome were screened for the presence of this disorder. Marfan syndrome was newly diagnosed in living members of 4 generations in this family without evidence of ocular abnormality in any. After screening, 10 relatives were newly diagnosed as having definite, and 5 relatives as having possible, Marfan syndrome. Family screening has drawbacks as well as benefits for the patients. The main benefit is the identification and treatment of previously undiagnosed patients at risk of cardiac complications which are the major cause of mortality. The drawbacks include employment problems created for patients with Marfan syndrome as a direct consequence of our screening programme and the anxiety induced in previously asymptomatic family members who did not realize that they could be at risk. Also, the 4 adult patients with possible Marfan syndrome found it difficult to accept that a definite diagnosis could not be reached after they had been invited to attend a screening programme for a serious genetic disorder. This report illustrates the importance of screening all the relatives of a patient with Marfan syndrome to identify previously undiagnosed cases. However, before screening a family, the physician should be aware that a clear diagnosis may not be reached in all patients, and financial, psychological or social problems may arise as a result of the screening programme. PMID- 1924023 TI - The effect of caffeine on postprandial blood pressure in the frail elderly. AB - In a double-blind, random-order, cross-over study the effects of placebo and 100 mg of caffeine on postprandial sitting and erect blood pressure and heart rate were studied in 20 frail elderly subjects (mean age 84, range 75-93 years) after a standardized 400 K-calorie glucose drink. Maximal postprandial reduction in sitting systolic blood pressure occurred, at 60 minutes post-placebo, of - 11 mmHg (95% confidence interval -5 to -17 mmHg, P less than 0.01), and was attenuated by caffeine (P less than 0.05) with changes in systolic blood pressure, at 60 minutes post-drink, of 1 mmHg (95% CI -6 to 7 mmHg, not significant). Four subjects developed symptomatic postprandial hypotension after placebo which was prevented by caffeine. There were no significant changes in erect systolic blood pressure, postural systolic blood pressure change, sitting and erect, diastolic blood pressure and heart rate between treatment phases. Caffeine attenuates the postprandial fall in sitting blood pressure in frail elderly subjects and in particular prevented symptomatic blood pressure reductions in subjects with postprandial hypotension. PMID- 1924024 TI - Safety and efficacy of fluconazole treatment for Candida oesophagitis in AIDS. AB - The efficacy and safety of fluconazole in the treatment of oesophageal candidiasis in patients with the acquired immunodeficiency syndrome (AIDS) was assessed in 36 patients. Fluconazole, 200 mg orally, was given on the first day, followed by 100 mg daily for 4 weeks. Clinical and mycological evaluation was performed in 31 patients at the end of treatment and 24 were also assessed after 8 weeks of starting treatment. In 1 patient fluconazole was discontinued, 5 patients were lost to follow-up and 6 patients died during the study. Clinical and mycological cure was achieved in all patients; in 31 of 36 patients the clinical picture resolved within a week. The cure was confirmed in 27 patients by oesophagoscopy. Two patients relapsed 1 month after stopping fluconazole but the reinstitution of therapy achieved cure. Asymptomatic fungal oropharynx colonization was evident in about 40% of patients during treatment and follow-up period. Fluconazole was well tolerated by all patients but mild to moderate increase of liver enzymes values occurred in 16. Treatment had to be discontinued in 1 patient with hepatic tuberculosis because of severe liver function abnormalities, but their relation with the drug was uncertain. Fluconazole is an effective and safe treatment of oesophageal candidiasis in AIDS patients. PMID- 1924021 TI - Neurology. PMID- 1924025 TI - Congenital hypothyroidism--correlation between radiographic appearances of the knee epiphyses and biochemical data. AB - Plain knee radiographs of 20 neonates with congenital hypothyroidism, were reviewed. The size and appearances of the epiphyses were compared with the biochemical data at the time of referral. Fifteen infants had unequivocal evidence of delayed bone maturation based on absence of the distal femoral epiphysis or small epiphyseal size. Seven cases had fragmentation of at least one epiphysis. A positive correlation was found, at diagnosis, between the thyroxine and triiodothyronine levels and the size of the knee epiphyses. All 14 infants with thyroxine levels of less than 70 nmol/l had small epiphyses with a combined mean diameter of the proximal tibial plus distal femoral epiphyses of 7 mm or less. Conversely, of the 6 infants with thyroxine levels of 70 nmol/l or above, 5 had combined epiphyseal diameters of greater than 10 mm. We suggest that in infants with no clinical symptoms and only moderately raised raised screening thyroid stimulating hormone, a knee radiograph showing the described radiological changes should prompt institution of thyroxine treatment before awaiting biochemical confirmation of the diagnosis. PMID- 1924026 TI - Pulmonary embolism: a cause of acute confusion in the elderly. AB - Large numbers of elderly patients are admitted to hospital with an acute confusional state. In many of these, the underlying cause is easily found, but in a proportion, correct diagnosis is very difficult. Two cases of acute confusion due to hypoxia are presented, in which the diagnosis of pulmonary embolic disease was made late. The importance of considering this in all patients presenting with acute confusion and the value of blood gas analysis is discussed. PMID- 1924027 TI - Arthritic presentation of childhood leukaemia. AB - Three cases of childhood acute lymphatic leukaemia masquerading as juvenile chronic arthritis are presented. All had symptoms and signs for at least 4 months before leukaemia was diagnosed and in two the full blood count was normal at presentation. The importance of a high index of suspicion is emphasized, particularly if the white cell count is low. PMID- 1924028 TI - The successful surgical repair of a ruptured interventricular septum following a myocardial infarct in an 89 year old man. AB - This case report describes the successful repair of an acquired ventricular septal defect following an anterior full thickness myocardial infarct in an 89 year old man. Four months after the infarct the patient was in severe congestive cardiac failure (NYHA Class IV), despite medical treatment, with signs of a ventricular septal defect. This was confirmed by echodoppler and cardiac catheterization. Surgical repair of the ventricular septal defect was performed. He made an uncomplicated recovery and two and a half years later is well and active. We believe he is the oldest patient who has had this operation successfully. PMID- 1924029 TI - Two varieties of rib notching. PMID- 1924030 TI - Cerebral neoplastic angioendotheleosis complicated by hypercalcaemia. AB - This is a case report of a 67 year old man who presented with a fluctuating level of consciousness and myoclonic jerks caused in part by hypercalcaemia. The diagnosis of cerebral neoplastic angioendotheleosis was only made later on brain biopsy and is the first report of the occurrence of hypercalcaemia in neoplastic angioendotheleosis. PMID- 1924031 TI - Crescentic transformation in primary membranous glomerulonephritis. AB - A 31 year old man first developed steroid-resistant idiopathic membranous glomerulonephritis in 1981. Stable normal renal function was maintained until August 1988 when he suffered a clinical relapse with heavy proteinuria and declining renal function. Immunosuppressive therapy with prednisolone and cyclophosphamide was instituted in an attempt to arrest this relapse. Despite this, he later developed acute renal failure with histological evidence of crescentic transformation of his nephritis. This unusual transformation was not associated with features of systemic vasculitis or positive anti-glomerular basement membrane and anti-neutrophil cytoplasmic antibodies. PMID- 1924032 TI - A resistant case of neurocystercercosis. PMID- 1924033 TI - Primary HIV-I infection associated with pneumonitis. AB - A 21 year old homosexual man presented with an acute pneumonitis during symptomatic seroconversion for human immunodeficiency virus (HIV-I) infection. The symptoms resolved spontaneously without any therapeutic interventions needed. Acute pneumonitis should be added to the ever-increasing spectrum of clinical manifestations in primary HIV-I infection. PMID- 1924034 TI - The Dieulafoy gastric malformation: an under-recognized cause of massive upper gastrointestinal haemorrhage. AB - The Dieulafoy gastric malformation is a rare cause of upper gastrointestinal haemorrhage. When no obvious bleeding lesion is seen at laparotomy this diagnosis ought to be considered. Three such cases were identified and treated with simple underrunning of the lesion with no mortality and minimal morbidity. Follow-up endoscopy in each patient showed complete healing of the lesion. PMID- 1924035 TI - Colonic involvement in Fabry's disease. AB - The case of a 54 year old man with Fabry's disease and extensive jejunal and colonic diverticulosis causing colonic stricture is presented. Histological examination of the resected colon revealed evidence of ceramide trihexose deposition in the myenteric nerve plexus. Colonic involvement in Fabry's disease has not been reported before. PMID- 1924036 TI - Therapeutic implications of diastolic dysfunction in heart failure. PMID- 1924037 TI - Withdrawal of maintenance digoxin from institutionalized elderly. PMID- 1924038 TI - Stroke due to carotid artery dissection. PMID- 1924039 TI - Rare presentation of gastric leiomyosarcoma. PMID- 1924040 TI - Mitral valve prolapse--do all patients need an echocardiogram? PMID- 1924041 TI - Myasthenia gravis and reversible pyramidal tract signs in a thyrotoxic patient. PMID- 1924042 TI - Pericardial tamponade resulting from changing a central venous catheter over a guide wire. PMID- 1924043 TI - Leukopenia and thrombocytopenia due to fusidic acid. PMID- 1924044 TI - Osteoporosis--an opportunity to prevent being missed. PMID- 1924045 TI - Bleeding peptic ulcer--endoscopic and pharmacological management. PMID- 1924047 TI - Lung function abnormalities and decline of spirometry in scleroderma: an overrated danger? AB - To document the prevalence and progression of pulmonary involvement in scleroderma (systemic sclerosis including the CREST syndrome), the clinical notes and lung function records of 113 cases were reviewed. Lung function was normal in 39 cases, isolated impairment of DLCO was found in 38 patients, a restrictive defect was present in 27 cases and there was evidence of airflow obstruction in 9 cases. The median duration of symptoms was 10 years. Dyspnoea and an interstitial pattern on chest X-ray were associated with impaired lung function. Death during the period of review was significantly related to initial impairment of the DLCO. Sixty-six patients (53 women and 13 men) underwent repeat spirometry at least 1 year after initial testing. The rates of change in VC and FEV1 were no more rapid than would be expected for normal subjects. There was no significant difference in rates of change between men and women or between dyspnoeic patients and those who were asymptomatic. The extent of skin involvement and the presence of interstitial fibrosis on chest X-ray were unrelated to the rate of loss of lung function. It is concluded that most scleroderma patients in this study had abnormal lung function when first tested, but overall significant worsening of spirometry was not found. PMID- 1924046 TI - Medical genetics. PMID- 1924048 TI - Transient hyperphosphatasaemia in association with acute infection in adults. AB - The causes of raised serum alkaline phosphatase were determined prospectively in a consecutive series of 2884 acute medical admissions. Diagnoses were established by pre-defined clinico-pathological criteria. Two hundred and four patients had hyperphosphatasaemia. Liver and bone disease accounted for only 98 (48%) of the established diagnoses. The diagnosis was not established in 31 (15%). Transient hyperphosphatasaemia occurred in 66 (32.4%) cases. In 25 of these patients (12% of the total) an acute infection was the sole illness identified. In this infected group, the isoenzyme type was predominantly hepatic, although jaundice occurred in only 3 patients. Discriminant analysis revealed that this group was characterized by haematological and biochemical features of an acute phase response. Transient hyperphosphatasaemia is commonly found in acutely ill medical inpatients and is frequently associated with acute extrahepatic infection. PMID- 1924050 TI - Bradyarrhythmias in acute myocardial infarction: should thrombolysis lower the decision threshold for temporary pacing? AB - Both acute myocardial infarction and reperfusion therapy with thrombolytic agents may be associated with bradyarrhythmias, and there may be a case for 'prophylactic' insertion of a temporary pacing wire in selected patients. We describe 4 patients in whom clinical decisions had to be made concerning the appropriateness and timing of temporary pacing, and discuss the implications for modern guidelines on the indications for pacing in such a setting. PMID- 1924049 TI - Hypernatraemia in an adult in-patient population. AB - We report a retrospective study of hypernatraemia (serum sodium concentration greater than 150 mmol/l) in an adult in-patient population of a health district during one year. The incidence was 0.3% with at least 60% of cases developing after hospital admission, mainly in elderly patients. Dehydration appeared to be the major cause, with the use of diuretics, depressed conscious level or febrile illness implicated in a majority. Most patients had more than one contributory factor and iatrogenic causes were common. Associated illnesses were often severe and the in-hospital mortality was high (54%) regardless of age. Hypernatraemia in hospitalized patients should be largely avoidable and there is a need for greater awareness of the importance of active maintenance of hydration in susceptible patients. PMID- 1924051 TI - Lipid profile studies in long term thiazide treated hypertensives. AB - Serum cholesterol and its subfractions were estimated in 23 patients on thiazide diuretics, for treatment of mild hypertension, for at least 30 months. The results were compared with those obtained in a matched set of 25 untreated mild hypertensives. It was found that while there was no difference in the level of total cholesterol, the LDL-cholesterol was significantly lower and HDL cholesterol significantly higher in the treated group. It was also found that the total:LDL-cholesterol ratio was more in the treated group and the total:HDL cholesterol ratio was less in the treated group. These findings suggest that coronary risk attributable to cholesterol and its subfractions does not seem to operate in long term thiazide treated patients. PMID- 1924052 TI - Interaction of ketoprofen and frusemide in man. AB - The effects of ketoprofen on frusemide-induced diuresis, natriuresis and renin release were studied in 12 healthy male volunteers. Each received frusemide 40 mg once daily with either ketoprofen 100 mg twice daily or placebo for two periods of 5 days separated by a treatment-free period according to a randomized, double blind, cross-over study design. Ketoprofen significantly reduced frusemide induced diuresis on Day 1 but not on Day 5 of treatment. The natriuresis induced by frusemide on Day 1 or Day 5 of treatment did not differ significantly whether ketoprofen or placebo was administered, although the mean urinary sodium excretion values were consistently lower following ketoprofen. Ketoprofen did not affect the kaliuretic response to frusemide on Day 1 or Day 5 of treatment. The increase in plasma renin activity after frusemide was inhibited by ketoprofen on both Day 1 and Day 5. These results suggest that ketoprofen reduces the diuresis and renin release induced by frusemide, but that the reduction in diuretic response may become less important after their repeated coadministration. PMID- 1924053 TI - Cardioversion of atrial fibrillation of recent onset with flecainide. AB - Twenty-eight patients with atrial fibrillation of less than 1 month's duration were given a single intravenous bolus of flecainide (2 mg/kg). Nineteen patients (68%) were successfully converted to sinus rhythm. Of the 19 patients with atrial fibrillation of less than 72 hours duration, 18 (95%) were successfully converted. Failure to cardiovert was associated with cardiomegaly on chest X-ray and larger left atrial diameter measured echocardiographically. Of the 9 patients who failed to convert, 2 had biochemical evidence of thyrotoxicosis and chronic obstructive pulmonary disease. Of the 19 patients successfully cardioverted, the atrial fibrillation complicated acute myocardial infarction in 3 cases and a pulmonary embolism in one. Six cases occurred post-operatively and in 3 out of 6 the patient was ventilated. No side effects were observed. The use of intravenous flecainide should avoid the need for electrical DC conversion even in sick patients. Failure of conversion is associated with covert underlying predisposing factors and duration of atrial fibrillation of more than 72 hours. PMID- 1924054 TI - Permanent pacemakers in nonagenarians. AB - We report our experience of 20 patients who have had permanent pacemakers implanted for the first time after the age of 90. The main indications were syncope or presyncope which occurred in 15 patients. Complete heart block was present in 14 patients. Syncopal and presyncopal symptoms were cured in 73%. Nonagenarians paced for complete heart block can expect to survive for as long as others of the same age without heart block. Permanent pacing is an effective and appropriate treatment in the very old. PMID- 1924055 TI - A new hypothesis for the aetiology of Crohn's disease--evidence from lipid metabolism and intestinal tuberculosis. AB - The stimulus for the immune response in Crohn's disease is unknown. In each of 19 cases of Crohn's disease evaluated by electron microscopy, epithelial cells of the ileum contained phagolysosomes with lamellar layers of lipid. These structures, now termed R or reactant bodies, are the proffered antigenic stimulus. They are proposed to be an amalgam of lipid (cholesterol esters, or phospholipids) and bacterial fragments (mycoplasma, mycobacteria or streptococci), which in combination are hypothesized to produce a powerful immunological response analogous to the adjuvant effect. For disease expression to occur, lipids and specific bacterial populations are needed in the bowel lumen. These factors may account for the success of elemental diets that are low in fat in the treatment of Crohn's disease and for the regional distribution of disease along the intestinal tract. PMID- 1924056 TI - Occult tuberculous postpneumonectomy space empyema four years after lung resection. AB - We describe a patient in whom a tuberculous postpneumonectomy empyema developed 4 years after resection for lung cancer. The clinical presentation was dominated by non-specific constitutional symptoms, without any chest complaints. A computed tomographic scan of the chest suggested inflammation in the postpneumonectomy space. Ultimately Mycobacterium tuberculosis was cultured from material aspirated by needle thoracocentesis. To our knowledge this is the first report of a tuberculous postpneumonectomy empyema complicating resection for cancer. PMID- 1924057 TI - Gynaecomastia and extragonadal symptoms leading to diagnosis delay of germ cell tumours in young men. AB - We report two young men with gynaecomastia in whom the underlying causative metastatic germ cell malignancies were not diagnosed for prolonged time periods. Despite the fact that cancer is an uncommon cause of gynaecomastia, doctors should consider germ cell malignancy, even in the absence of testicular symptoms or signs, in previously healthy young men with recent gynaecomastia or other unusual symptoms or signs. Serum beta human chorionic gonadotrophin and other germ cell malignancy markers (alpha fetoprotein and lactic dehydrogenase) should always be assayed. If a testicular primary site is not clinically apparent, there should be early recourse to scrotal ultrasonography. PMID- 1924058 TI - Massive chloroquine overdose--a survivor. AB - Large chloroquine overdoses are almost inevitably fatal. We describe the presentation and management of a patient with such an overdose who survived, due to general supportive care and new specific treatment. PMID- 1924059 TI - Histiocytosis X involving the thyroid and hypothalamus. AB - A case of histiocytosis X involving the thyroid and hypothalamus is reported. A 16 year old female presented with amenorrhoea and diabetes insipidus. She subsequently developed a painful goitre with biochemical hypothyroidism, and stridor. The stridor and goitre responded to cyclophosphamide. Previous publications on the use of cytotoxics in histiocytosis X involving the thyroid are reviewed. We describe for the first time both the ultrasound appearances of the thyroid in this condition and the use of serial volumetric measurements to monitor therapy. PMID- 1924060 TI - A solitary jejunal vascular abnormality: a source of massive rectal bleeding. AB - Haemorrhage of small bowel origin may prove to be a clinical and diagnostic challenge, particularly when the bleeding is massive and continuous. Such a case is described where the source of blood loss was a jejunal vascular abnormality. PMID- 1924061 TI - Evisceration and other complications of abdominal drains. AB - Drainage following major abdominal surgery remains controversial. A case of small bowel evisceration through a Wallis drain site after an abdomino-perineal excision of rectum is reported as a complication of abdominal drainage. PMID- 1924062 TI - Delayed haemolytic transfusion reactions in patients with sickle cell disease. AB - We describe two cases which illustrate the difficult diagnostic and therapeutic problems posed by delayed haemolytic transfusion reactions in patients with sickle-cell disease. The cases emphasize the need for meticulous phenotypic and serological assessment of sickle-cell patients prior to transfusion therapy. PMID- 1924063 TI - Diverticulum of a Meckel's diverticulum containing a stone. AB - An 18 year old girl presented with acute abdominal pain and a calcified opacity in the pelvis. She proved to have a Meckel's diverticulum which had a secondary diverticulum at its apex, containing a stone. Meckel's stones are uncommon and diverticula of a Meckel's diverticulum exceedingly rare. This is only the second recorded case of such a diverticulum containing a stone, and the first to describe a calcified stone in this location. PMID- 1924064 TI - Hyposplenism and streptococcal sepsis. PMID- 1924065 TI - Typhoid hepatitis with pancytopenia. PMID- 1924066 TI - Nasogastric catheter fastening technique. PMID- 1924067 TI - Colonic tuberculosis with colonic carcinoma--a rare association. PMID- 1924068 TI - Hashimoto's thyroiditis associated with acquired idiopathic demyelinating polyradiculoneuropathy. PMID- 1924069 TI - Fatal rupture of a subcapsular liver haematoma in a patient treated with anisolylated plasminogen streptokinase activated complex. PMID- 1924070 TI - Advances in understanding alcohol withdrawal states. PMID- 1924071 TI - CT and MR imagings of single thyroid lobe (thyroid hemiagenesis) with Graves' disease. PMID- 1924072 TI - Carotid artery disease presenting as cough headache in a patient on haemodialysis. PMID- 1924073 TI - Hypereosinophilia and acute lymphocytic leukemia. PMID- 1924074 TI - The cardiovascular effects of dobutamine assessed by magnetic resonance imaging. AB - Magnetic resonance imaging is a new technique for the investigation of cardiac anatomy and function, but few attempts have been made to assess its value in the evaluation of coronary artery disease because of the problems of performing exercise in the magnet. In this review, we describe our experience using dobutamine as a substitute for exercise. We have assessed regional left ventricular wall motion by cine magnetic resonance imaging and global function from aortic flow and acceleration measurements using cine magnetic resonance velocity mapping. We studied regional wall motion in 23 patients presenting for coronary angiography because of chest pain. Of 21 with reversible dobutamine induced thallium perfusion defects, 20 (95%) had dobutamine-induced wall motion abnormalities corresponding closely in site and size. We studied aortic flow in 25 similar patients and we compared the results with five normal volunteers with a low likelihood of coronary artery disease. A failure to increase peak aortic flow acceleration (peak, rate of change of flow) by 15 L/s2 was the most significant parameter associated with coronary artery disease. A reduction in peak flow acceleration at peak stress occurred in patients with moderate or severe myocardial ischaemia as determined by thallium myocardial perfusion imaging. Dobutamine is a valuable pharmacological agent which can induce regional and global abnormalities of left ventricular function in patients with coronary artery disease during magnetic resonance imaging. PMID- 1924075 TI - Evaluation of cardiac dysfunction, cardiac reserve and inotropic response. AB - The assessment of cardiac function and dysfunction has often concentrated on particular but piecemeal aspects of ventricular performance. This leads to diverse and often opposite claims on how to define, evaluate and treat heart failure. This review adopts a more integrative approach of appraising the heart, putting it in the context of its role in the circulation. The emphasis is to find a variable which would evaluate the overall function of the heart. Several objective criteria on how to select such a variable were proposed. It was argued that of all currently available variables, cardiac power output fulfils these requirements best. It has long been recognised that cardiac performance assessed at basal resting states do not reflect how much reserve the cardiac pump possesses. Having a variable which represents overall cardiac function implies that cardiac pumping capability and reserve can now be quantified. Cardiac reserve has been found to be a major determinant of exercise capacity in heart failure, and pumping capability a major determinant of prognosis in patients with severe heart failure. Therapeutic attempts at improving the exercise capacity of heart failure patients should be gauged against their ability to improve cardiac reserve. Inotropic agents that augment myocardial performance but compromise cardiac reserve do not improve exercise capacity. An ideal inotrope is one that is synergistic with the sympathetic system and enhances cardiac performance only during exercise. PMID- 1924076 TI - Pharmacological stress echocardiography in the evaluation of coronary artery disease. AB - This article deals with the application of pharmacological stress echocardiography, a relatively new and evolving technique, to the diagnosis and assessment of patients with coronary artery disease. The value of echocardiography in ischaemic heart disease is initially outlined, followed by a brief review of the exercise two-dimensional echocardiography and exercise echo Doppler literature. Dipyridamole, adenosine and dobutamine stress echocardiography are then examined, and the rationale and potential advantages of this approach explained. The findings of our own work using dipyridamole and dobutamine stress, combined with both two-dimensional echocardiography and Doppler, are then described. A review of the various methods of echocardiographic image analysis is then presented and the article concludes by suggesting directions for future work. PMID- 1924078 TI - The assessment of the microcirculatory effects of dobutamine using mercury in silastic strain gauge plethysmography in man. AB - Adverse changes in the microcirculation are currently considered as the most likely common pathway of organ failure, dramatically manifest in the multiple organ failure syndrome. We have investigated 28 patients presenting with gross cardiovascular instability due to septic shock or haemorrhage, using standard invasive methods of monitoring (Physiological Profile). We combined this study with a computer assisted mercury-in-rubber strain gauge plethysmography (MSG) measurement, for a parallel (non-invasive) assessment of peripheral microcirculatory function. We started the investigation on patient arrival in ICU and continued it during their resuscitation regime, which essentially consisted of fluid loading together with inotropic support, where necessary. We found highly significant changes in isovolumetric venous pressure (Pvi), determined by the MSG technique, when we compared survivors (27.29 +/- 1.65 mmHg, mean +/- s.e.m.) with non-survivors (39.5 +/- 2.97 mmHg, P less than 0.001). To investigate the role of dobutamine in patient improvement we compared the Pvi values obtained from the MSG studies and demonstrated a significant decrease from the initial value (38.2 +/- 2.4 mmHg) to the final one (25.4 +/- 2.4 mmHg), obtained after weaning the patients off dobutamine. Marked cyclic changes in limb circumference (vasomotion) were also observed and their appearance correlated well with accepted parameters of cardiovascular instability. We propose that changes in both Pvi and Vm are useful indices of microvascular hypoperfusion which is probably the underlying cause of pathology in both patient groups. PMID- 1924077 TI - Goal directed therapy with dobutamine in a porcine model of septic shock: effects on systemic and renal oxygen transport. AB - Systemic and renal haemodynamic and functional indices were measured in 15 anaesthetised pigs during systemic sepsis induced by faecal peritonitis. Five animals were assigned to maintenance of cardiac output (CO) at baseline, pre infection values throughout the study (controls n = 5). In the remaining 10 animals, CO was increased by 25% prior to induction of sepsis and maintained at this level for the duration of the study using volume expansion with intravenous colloid and an infusion of either 20 micrograms/kg/min dobutamine (n = 5) or placebo (n = 5). Hourly measurements were made of CO, left renal blood flow, arterial and renal venous oxygen saturation, urine output, creatinine clearance and arterial partial pressure of oxygen until the animal died or until termination 8 h. Systemic indices of oxygen transport did not reflect the behaviour of the renal vascular bed during the management of sepsis. In the dobutamine group systemic oxygen uptake (VO2) increased from 173 +/- 30 to 277 +/ 73 ml/min (P less than 0.05), however this resulted in a decrease in renal DO2 (20 +/- 9 to 10 +/- 2 ml/min P less than 0.05) and there was no equivalent rise in renal VO2 (3.3 +/- 1.6 to 3.2 +/- 1.5 ml/min). There was however no significant difference in the effect on renal function of the three management protocols. Agents used to increase cardiac output during systemic sepsis may result in significantly different effects on the renal vascular bed which are not revealed by the measurement of systemic indices alone. PMID- 1924079 TI - The effect of dobutamine on middle cerebral artery blood velocity in volunteers: a preliminary study. AB - Five volunteers given dobutamine up to 4 micrograms/kg/min had significant increases in mean arterial blood pressure, systolic blood pressure, and stroke volume (P less than 0.05). Heart rate did not increase significantly. Pulsatility index, an index of middle cerebral artery maximum blood velocity waveform shape increased significantly in the dobutamine group (P less than 0.05). Time-averaged mean velocity did increase during the dobutamine infusion but the change was not statistically significant. Dobutamine significantly alters the blood velocity profile of the middle cerebral artery in volunteers even in low doses of 4 micrograms/kg/min. Transcranial Doppler may be a useful technique to monitor changes in cerebral artery blood velocity dynamics induced by dobutamine. These measurements can be performed easily and repeatedly at the bedside. PMID- 1924080 TI - Lactate and acid base changes in the critically ill. AB - Metabolic acidosis and hyperlactataemia are important, independent findings in acute illness, and the combination of these abnormalities carries a grave prognosis. Despite this there is still controversy about the most appropriate therapy of lactic acidosis, and the relationship of commonly used acid base measurements to blood lactate levels. This paper details studies in shock and multiple organ failure examining these issues. Shocked patients were studied during catecholamine therapy and showed improvements in acidosis and hyperlactataemia in conjunction with cardiorespiratory improvement. This supports a beneficial role for these agents in appropriately monitored, volume resuscitated and oxygenated patients with shock and lactic acidosis. Assessment of differences in mixed venous and arterial acid base status was performed in 32 patients. The relationship of blood lactate to acid base measurements was examined. There were no significant differences in [H+], [HCO3] or base excess. There was no significant correlation between any of these in arterial or mixed venous samples and arterial whole blood lactate. Mixed venous PCO2 was significantly higher than arterial PCO2. Haemodynamic, oxygen transport and acid base changes were documented in eight patients with multiple organ failure being treated by intermittent high volume haemofiltration (Gambro AK10 system) with lactate buffered replacement fluid PCO2 (Gambro haemofiltrasol). Cardiac output and oxygen delivery fell significantly during therapy but blood pressure was maintained by an increase in systemic vascular resistance as we have shown previously. Serious acid base derangements were not seen. Significant hyperlactataemia was present throughout haemofiltration as a result of the infusion of replacement fluid containing 45 mmol/l lactate. The only alterations in acid base status were transient falls in arterial bicarbonate and base excess at one hour. PMID- 1924081 TI - Dobutamine stress testing in chronic heart failure--dose-response effects assessed by echo-Doppler. AB - In patients with cardiac failure, data on haemodynamic function at rest may indicate impaired cardiac function but do not assess the capacity of the heart to respond to stress which may be useful in determining prognosis. Inotropic challenge with dobutamine has been shown to be at least as effective as exercise testing in assessing cardiac pumping capability. One of the limitations of dobutamine stress testing has been the need for invasive haemodynamic measurements. A new non-imaging echo-Doppler cardiac output device, incorporating the principle of attenuated compensation volume flow (ACVF), has been shown to be accurate, reproducible and useful in pharmacodynamic studies. In this study we examined the dose-response effects of dobutamine in 8 patients with chronic heart failure. Dobutamine was infused at 2, 5, 10 and 15 micrograms/kg/min with the dose being increased at 5 minute intervals and haemodynamics being determined (using the echo-Doppler) in the final 2 minutes of infusion. Our results were comparable to previous studies. There were dose-related increases in heart rate (P less than 0.05), cardiac output (P less than 0.05), and cardiac power output (work done by the heart per unit time) (P less than 0.05). Systolic blood pressure increased (P less than 0.001) and there were modest increases in mean arterial blood pressure without change in diastolic blood pressure. Time averaged mean velocity increased significantly with a trend to increase in flow acceleration. Three patients developed arrythmias during the early recovery period. The echo Doppler attenuated compensated volume flow method of determining haemodynamics proved useful but in view of the high incidence of dysrhythmia we feel that dobutamine testing in severe heart failure should be employed cautiously. PMID- 1924082 TI - Physical and pharmacological conditioning in chronic heart failure: a proposal for pulsed inotrope therapy. AB - There is good evidence that physical deconditioning may be playing an important role in the changes secondary to chronic heart failure, and that it may contribute to exercise intolerance. Physical training can improve the symptoms and exercise performance of patients in stable chronic heart failure and the possibility is discussed that pharmacological therapy may be able to stimulate some of these benefits. A protocol for pulsed inotrope therapy is proposed which may produce pharmacological conditioning whilst avoiding drug tolerance and beta receptor down-regulation and lessening the incidence of arrhythmias. PMID- 1924083 TI - Peripheral abnormalities in chronic heart failure. AB - Exercise intolerance is a major cause of morbidity in chronic heart failure (CHF) and has traditionally been attributed to skeletal muscle hypoperfusion during exercise. However, intrinsic abnormalities in skeletal muscle biochemistry and histology may also play an important role in the pathophysiology of exertional fatigue in CHF. Studies using 31P nuclear magnetic resonance (NMR) spectroscopy have demonstrated early skeletal muscle metabolic changes during exercise including excessive acidification and phosphocreatine depletion. Patients with CHF show muscle fibre atrophy with transformation of type I to II fibres accompanied by a decrease in oxidative enzyme capacity. Most of the drugs currently used to treat patients with CHF do not improve oxygen availability within exercising muscle or exercise capacity although some of them increase blood flow to skeletal muscle or alter the pattern of blood flow distribution. Physical training programmes improve exercise performance, ventilation, autonomic function and symptomatic status in CHF. Training can also increase cardiac output and reduce peripheral vascular resistance with concomitant increases in blood flow to exercising muscle and reduced arterial and venous lactate. 31P-NMR studies in patients with CHF have demonstrated significantly less acidification and phosphocreatine depletion during exercise after physical training. Animal studies suggest that the NMR changes in skeletal muscle of CHF depend on both the severity of heart failure and physical deconditioning, whereas training may reverse or prevent these alterations. PMID- 1924084 TI - Residual feed consumption in laying hens. 1. Quantification of phenotypic variation and repeatabilities. AB - A large fraction (on average, 25%) of the variance of daily feed consumption among individual laying hens appears unaccounted for by a model with metabolic body weight, daily egg mass production, and body weight gain as independent variables. This unexplained term is referred to as "residual feed consumption" (RFC), defined operationally as the difference between the observed feed consumption of a hen and its consumption as predicted from the model. The study described here deals with the quantification of the phenotypic variation of RFC of hens of a White Leghorn population during a 44-wk laying period (20 to 64 wk of age) in 11 time segments of 4 wk each, fed either a commercial or a low-energy diet (11.7 and 10.0 MJ ME/kg, respectively, where 1 MJ = .239 Mcal). The RFC showed a standard deviation of 4 to 8 g/day. The repeatability of RFC was estimated as .52 to .58. For each time segment between 32 and 56 wk of age, phenotypic correlations between RFC and RFC accumulated over the whole laying period were estimated to be around .8. It was concluded that RFC shows a considerable amount of systematic and permanent variation, and that experimental RFC measurements can be limited to the period between 32 and 56 wk. It was also shown that variation in RFC was caused mainly by differences among hens in maintenance requirements per unit (kilogram.75) of metabolic body weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1924085 TI - Residual feed consumption in laying hens. 2. Genetic variation and correlations. AB - The study described here deals with the quantification of the genetic variation of "residual feed consumption" (RFC) of hens of a White Leghorn population during a 44-wk laying period (20 to 64 wk of age) in 11 time segments of 4 wk each, fed either a commercial or a low-energy diet (11.7 and 10.0 MJ ME/kg, respectively, where 1 MJ = .239 Mcal). The RFC is defined operationally as the difference between the observed feed consumption of a laying hen and its consumption as predicted from a model with metabolic body weight, egg mass production, and body weight gain as independent variables. The RFC was found to be highly heritable in all periods. The heritability of RFC accumulated over the whole laying period (RFC-T) was estimated as .42 to .62. For each time segment between 32 and 56 wk of age, genetic correlations between RFC and RFC-T were estimated to be larger than .91. The genetic sources causing variation in RFC during the first part of lay seem to differ from those causing variation later on, and to be of less importance during the rest of the laying period. It was concluded that RFC shows a considerable systematic and permanent additive genetic variance, and that RFC measurements for selection can be limited to one to three time segments between 32 and 56 wk. Furthermore, less environmental variance and therefore higher heritabilities and genetic correlations seemed to exist for birds fed the low energy diet in comparison with those fed the commercial diet. No clear differences could be found between genetic and phenotypic correlation estimates of RFC with feed consumption, metabolic body weight, egg mass production, and body weight gain. PMID- 1924086 TI - Genetic and phenotypic relationships in Japanese quail. 1. Body weight, carcass, and organ measurements. AB - Live BW, carcass data, and organ data taken at 34 days of age on approximately 1,000 quail of both sexes from 110 sires and 290 dams were utilized to estimate genetic parameters from the initial generation of a selection study. The birds represented a sample of a line selected for high 4-wk BW. Data were analyzed using Henderson's Method 3 (MM3) and restricted maximum likelihood (REML) with and without a relationship matrix. The paternal half-sib heritabilities for body, carcass, and organ weights in Japanese quail were moderate to high for most traits studied, suggesting that selection to increase or decrease these traits should be successful. With the exception of BW, abdominal fat (AF), and heart weights, maternal half-sib heritability estimates were smaller than paternal half sib estimates. Heritability estimates of traits adjusted for BW tended to be lower than counterparts not adjusted for BW. The genetic correlations of BW with the other carcass measurements were positive, and tended to be moderate to high. The correlation of BW with AF was .34, suggesting that selection for increased BW alone will lead to a bird with more abdominal fat. The correlations of AF with the other traits tended to be low to moderate in magnitude, with three of the correlations being negative, suggesting correlated responses with other traits when selecting for increased or decreased AF would be small. Genetic correlations among various muscle measurements were all positive and most were high in magnitude, indicating that traits easiest to measure and collect can be used in a selection process. The genetic correlations among the organ measurements were positive and moderate as were the correlations of organ weights with muscle weights. Negative genetic correlation estimates between AF and muscle measures were obtained from analysis when BW was a covariate. The REML heritability estimates were higher than MM3 estimates and REML genetic correlation estimates were less extreme than MM3. PMID- 1924087 TI - Association of body weight and feed separation to pen (cage) location for single comb White Leghorn pullets fed with a drag chain-type feeder. AB - A field study was conducted to determine the relationship of pen (cage) location (PL) along a drag chain-type feeder to BW and feed nutrients (FN) for commercial Single Comb White Leghorn pullets. At 12 and 17 wk of age, feed samples were collected and BW was measured individually for 1 pen (cage) at approximate 30-m intervals from 0 to 213 m. Replication was two lines per house, two houses per farm, and three farms at two ages. Feed was analyzed for CP, fat, P, K, Ca, Mg, Zn, Cu, Na, and moisture. Means for BW and FN were regressed on PL using a general linear model. Body weight increased (P less than or equal to .05) as PL increased from 0 to 213.36 m along the feed line. For the nutrients CP, K, Mg, Na, and moisture, there was no PL effect. For the nutrients fat, Zn, and Mn, there was a significant PL and week effect with a significant PL by week interaction. For the nutrients P, Ca, and Cu, there was a significant PL and week effect but no significant PL by week interaction. Body weight was correlated negatively with Zn and positively with K and Mn for 12 wk of age only. Feed separation along a drag chain-type feed line did occur. However, the relationship of feed separation to changes in BW was not fully ascertained in the present study. PMID- 1924088 TI - Performance evaluation of heat-stressed commercial broilers provided water-cooled floor perches. AB - A study was conducted to determine whether water-cooled floor perches would be utilized by commercial broilers exposed to a constant hot ambient environment; and subsequently, whether utilization of these perches would improve performance beyond those provided uncooled floor perches. A total of 330 day-old commercial broiler chicks were randomly allocated to six pens (2.44 m2) in an environmentally controlled facility and maintained in a thermoneutral brooding environment for 16 days. Following this period, 240 birds were selected on a body weight basis and randomly assigned to the six pens. A perch constructed from steel pipe (2.44 m length, 5.0 cm diameter) was then placed diagonally on the litter covered floor of each pen. The birds were first exposed to a thermoneutral period (27.7 C), during which time cooling of the perches in three replicate pens was initiated by circulating tap water. The other three experimental pens received ambient perches. Ambient temperature was then raised to 32.6 C for the following 4 wk. The results of the present study showed that utilization of water cooled perches by broilers was greater (P less than or equal to .01) than ambient perch utilization throughout the 32.6 C period. Average daily gain was greatest (P less than or equal to .01) for broilers exposed to cool perches. Additionally, they consume more feed (P less than or equal to .05), on a daily basis, than those given ambient perches during the heat-stress period. Broilers exposed to water-cooled perches also had a more efficient gain to feed ratio (P less than or equal to .01). At the completion of the study, final body weight and total body weight gain were greater (P less than or equal to .05) for broilers given water cooled perches compared with those exposed to ambient perches. Total amount of feed consumed and total feed efficiency were only moderately affected (P less than or equal to .10) by perch treatments. These results indicated that water cooled perches were beneficial in improving broiler performance during periods of high environmental temperatures. PMID- 1924089 TI - A retrospective analysis on the epizootiological aspects of outbreaks of Pasteurella anatipestifer infection in turkeys in Minnesota. AB - The possible risk factors associated with outbreaks of Pasteurella anatipestifer infection in turkeys were analyzed to study the epizootiology of the disease. The data for the study was obtained from flocks affected and unaffected with Pasteurella infection. The results of the analysis suggested that overcrowding, preexisting viral infections, increased activity of wild birds on the farm, and shorter down time were possible factors that initiate the occurrence of the disease in turkey flocks. The statistical models used in the analysis predicted correctly 80% of the unaffected flocks (8 out of 10 flocks), and 95% of the affected flocks (13 out of 14 flocks). The overall correct prediction was 88% (21 out of 24 flocks). Fish meal and meat and bone meal, which are integral components of turkey feed, were analyzed for the possible presence of P. anatipestifer. Its presence in a sample of fish meal was demonstrated. PMID- 1924090 TI - Vitamin E as adjuvant in emulsified vaccine for chicks. AB - Mineral oil was partially replaced with D, L-alpha-tocopheryl acetate (vitamin E) in bacterial and viral inactivated emulsified vaccines. Vitamin E increased the immune response to the viral antigen (Newcastle disease virus) used but not to the bacterial antigen (Escherichia coli) when its presence in the oil phase did not exceed 30%. Inoculated vitamin E may have enhanced the immune response by interacting with the immune-competent cells involved in the inflammatory reaction that followed inoculation of emulsified vaccines. PMID- 1924091 TI - The value of supplemental biotin for increasing hatchability of turkey eggs. AB - Two experiments were conducted with Large White Turkey hens in individual cages to determine the value of supplemental biotin for increasing hatchability. No differences were observed for 7-day embryo deaths between treatments in both experiments. In the last two-thirds of the production cycle in both experiments, eggs from hens fed 520 micrograms and 623 micrograms/kg had the fewest embryonic deaths during Days 7 to 28 of incubation. Concentrations of biotin in egg albumen increased with incremental dietary biotin levels, but egg yolk concentrations were stable. About 38 micrograms of biotin per egg (82 g) produced highest embryo survival. Regression analysis, based on average percentage hatchability at the treatment levels for both experiments, revealed no hatchability response for Period 1 (first third of production cycle) from biotin. However, the dietary biotin level for hatchability increased with maternal age, which ranged from 500 to 800 micrograms/kg for Periods 2 (second third of production cycle) and 3 (last third of production cycle), respectively. PMID- 1924092 TI - Growth and development of Leghorn pullets subjected to abrupt changes in environmental temperature and dietary energy level. AB - Four trials were conducted to note the response of pullets to changes in environmental temperature and energy level at 56 days of age. In each trial, birds were fed diets providing either 2,500 or 3,000 kcal ME/kg throughout rearing, or with a single diet change from 2,500 to 3,000 and 3,000 to 2,500 kcal ME/kg occurring at 56 days. Each of the four diet scenarios was tested with six replicate caged groups each containing 10 pullets. In Trials 1 and 2 environmental temperature was maintained at 18 and 30 C, respectively, to 126 days. In Trials 3 and 4, temperature was changed at 56 days from 18 to 30 C and 30 to 18 C, respectively. Regardless of environmental temperature conditions, diet change per se had minimal effect on growth and development. Rather dietary energy level used from 56 to 126 days had the greatest effect on growth, with birds fed the highest energy content diet generally being heaviest. However, this effect was not significant (P greater than .05) in all trials, which is probably related to a lack of effect on energy intake under such conditions. Final body weight was more closely associated with energy intake than with protein intake and energy intake was maximized when high-energy diets were used after 56 days of age. Consumption of high-energy diets after 56 days, regardless of trial conditions, always resulted in increased carcass fat content at 126 days. It was concluded that abrupt and major changes in environmental temperature or dietary energy as used in these trials have little deleterious effect on pullet development. Conditions prevailing during later stages of growth have a far greater effect than changes per se in these parameters. PMID- 1924093 TI - Myosin isoform expression in skeletal muscles of turkeys at various ages. AB - The appearance of myosin isoforms in skeletal muscles of turkey embryos, poults, and toms was studied, using monoclonal antibodies raised against myosin isoforms in chicken fast-twitch muscle (Pectoralis). The myosin extract was prepared by repeated salt extraction-precipitation. The reactivity of monoclonal antibodies with turkey myosin isoforms was tested by an enzyme linked immunosorbent assay using alkaline phosphatase-conjugated antibody and detection by color development with p-nitrophenyl phosphate. Detection was also effected by protein slot blotting using peroxidase-conjugated antibody and color development with 3,3' diaminobenzidine tetrahydrochloride. The monoclonal antibody AB8 was found to be specific for the adult myosin isoform, present in Pectoralis muscle of 14-day-old and adult turkeys and adult chickens. Subsequent peptide mapping also indicated that the adult myosin isoform of turkey Pectoralis muscle was nearly identical to the adult isoform from chickens. The monoclonal antibody 2E9 reacted with the myosin extract only from poults at ages of 7 days and 14 days posthatch, indicating that 2E9 is specific for the neonatal myosin isoform. The reactivity of 2E9 was noted with the muscle of the mixed fiber type (the thigh muscle group) as well as with the fast-twitch muscle (Pectoralis). Monoclonal antibodies EB 165 and AG6 were found to react with the myosin extract from all ages tested. Based on the reactivity with monoclonal antibodies, it was concluded that myosin in turkey muscles existed as at least three discrete isoforms that were expressed sequentially in the course of muscle development. PMID- 1924094 TI - The relationship between feed intake and frequency of the migrating motor complex in domestic turkeys: is there a cephalic phase? AB - Two studies were performed in order to test for the presence of a cephalic inhibition of migrating motor complexes (MMC) in domestic turkeys. Birds were implanted with two or three strain gauge transducers on the ileum and subjected to one of two different protocols. In Study 1 recordings of ileal motility were made under three feeding conditions: fed, fasted, and with feed pans in place before the birds but covered with plexiglass. In Study 2 the birds were either fasted, fasted with feed pans returned as soon as an MMC registered in the most orad gauge, or fasted with a minor disruption in the room (to simulate feed pan return) as soon as an MMC registered in the most orad gauge. Data from trials involving plexiglass plates did not differ significantly from data from fasted birds, and both differed significantly from the data from fed birds. Likewise, no significant differences were seen among any of the three feeding categories of Study 2. The present data show that neither the anticipation of eating, nor the presence of feed in the mouth and esophagus seem to directly influence the initiation or propagation of ileal MMC contractile activity in turkeys, supporting the view that extrinsic neural pathways are not responsible for the inhibition of the MMC. PMID- 1924095 TI - Growth hormone and insulin-like growth factors in poultry growth: required, optimal, or ineffective? AB - With a continually expanding market for poultry meat products, increased production demands of as much as 50% by the Year 2000 have been predicted. Indications already exist that this magnitude of expansion is not likely to be met by increased production output and genetic selection alone, and that other methods of improving growth performance per bird via exogenous manipulation of the growth process are needed. Studies in mammalian species clearly demonstrate the importance of growth hormone (GH) and its potential for enhancing productivity in domestic mammals. However, the role of GH in growth of poultry appears to be much more complex. Taken collectively, studies to date indicate that significant, positive effects of GH on growth performance of normal, growing poultry are possible. Expression of such effects appear to be largely contingent on the period of posthatch development (late posthatch being more responsive than early), and the pattern of several key metabolic regulatory hormones resulting in response to GH. Such regulatory hormone responses are largely influenced by the pattern or magnitude of exposure (acute versus chronic) to GH in birds. At this time, the available information on the potential for insulin-like growth factors to enhance growth is limited, and further studies are needed before a definitive role for these peptides in growth and development of poultry can be assigned. PMID- 1924096 TI - Partitioning of nutrients for growth and other metabolic functions: efficiency and priority considerations. AB - The raw materials for proteinaceous growth in the avian are amino acids supplied from protein ingestion and from body protein degradation. Maximal efficiency of utilization (i.e., retention) of absorbed nitrogen approximates 76%. This occurs when a well-balanced mixture of amino acids is ingested. The utilization efficiency of individual dietary amino acids varies around the 76% figure, with slow-turnover amino acids such as lysine being used more efficiently (80%) than fast-turnover amino acids such as isoleucine (61%). A paucity of information exists on metabolic priorities for amino acids at various levels of amino acid deficiency. It is clear, however, that dietary histidine is used with priority for protein synthesis before it is shunted toward carnosine or anserine biosynthesis. Likewise, cysteine use by chicks for growth has priority over cysteine use for glutathione (GSH) biosynthesis. With a cysteine-free diet containing the minimal methionine requirement for maximal growth, hepatic GSH is depressed and remains low and unchanged until about 30% of the growth need for cysteine is satisfied, at which point GSH begins accumulating rapidly. In rats, liver GSH begins accumulating rapidly even with very small doses of cysteine. This suggests that the metabolic priority for cysteine in rats is as great for GSH synthesis as it is for growth. PMID- 1924097 TI - The role of the growth plate in longitudinal bone growth. AB - The epiphyseal growth plate is the main site of longitudinal growth of the long bones. At this site, cartilage is formed by the proliferation and hypertrophy of cells and synthesis of the typical extracellular matrix. The formed cartilage is then calcified, degraded, and replaced by osseous tissue. Proliferation and differentiation of cartilage cells (i.e., chondrocytes) as studied mostly in culture, is regulated by various endocrine, paracrine, and autocrine agents such as growth hormone, insulin-like growth factor-I (IGF-I), transforming growth factor (TGE-beta), and vitamin D metabolites (1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol). Avian chondrocyte proliferation is enhanced by agents which use adenosine 3':5'-cyclic monophosphate as a second messenger, such as parathyroid hormone or prostaglandin-E2, and is depressed by guanosine 3':5' cyclic monophosphate agonists, such as atrial natriuretic peptide. Several of the regulating agents also affect synthesis of the main extracellular components (i.e., collagen and proteoglycans) and their transfer to the extracellular space. Cartilage calcification involves matrix vesicles secreted by the chondrocytes at a specific stage. Calcification probably involves some initial nucleation agent and participation of phosphatases. During sexual maturation, the growth plate closes by an unknown mechanism and longitudinal bone growth ceases. Disorders in the metabolism of the controlling agents or the cellular responses in growth plate may lead to several deformities classified as dysplasias. In poultry, this class of disorders is represented by chondrodystrophy and dyschondroplasia. PMID- 1924098 TI - Myogenic cell proliferation and differentiation. AB - It is generally thought that growth factors play a major role in regulating proliferation and differentiation of myogenic cells. Cell culture studies indicate that of the known growth factors, the fibroblast growth factors, the transforming growth factor beta, and the insulin-like growth factor families play the most significant roles in this process. The fibroblast growth factors stimulate proliferation and inhibit differentiation of most cultured myogenic cells. Insulin-like growth factors also stimulate proliferation of myogenic cells, but, in contrast to the fibroblast growth factors, the insulin-like growth factors also stimulate differentiation. Transforming growth factor beta inhibits differentiation of cultured myogenic cells. There are conflicting reports as to its effect on proliferation. The combined effects of these growth factors in vivo may play a major role in determining the rate of proliferation and differentiation of muscle tissue. PMID- 1924099 TI - Research note: T-cell activity of White Leghorn chickens selected for high and low antibody responses to sheep erythrocytes. AB - Mitogen responses of peripheral blood lymphocytes (PBL) and the cell cycle analysis of T-cells were examined for lines of chickens selected for high (HA) and low (LA) antibody response to SRBC. At 6 wk of age, within each line, blood samples and thymic tissue were collected from chicks representing the B13B13, B13B21, B21B13, and B21B21 genotypes. Although no influence of Ea-B haplotype on T-cell activity was detected in either line, there were line differences in phytohemagglutin-M (PHA-M) and concanavalin A (Con A) mitogen responses and the percentage G0/G1 and S phase T-cells. The HA PBL had greater in vitro PHA-M and Con A responses, and the cell cycle analysis of T-cells revealed a greater percentage of cells in S phase for Line HA chicks than for LA chicks. There were significantly more resting cells in the G0/G1 phase of LA than HA chicks. Although there was no Ea-B haplotype effect observed on T-cells from either line, generalized selection for high or low antibody response did result in divergent T cell activity. PMID- 1924100 TI - Research note: use of fenbendazole for the treatment of turkeys with experimentally induced nematode infections. AB - Turkeys were raised under parasite-free conditions until 25 days of age at which time the birds were administered infective ova of Capillaria obsignata, Heterakis gallinarum, and Ascaridia dissimilis. At 28 days postinfection, four groups of birds were placed on rations medicated with fenbendazole at 15,30,45, or 60 ppm. These rations were given ad libitum for 6 consecutive days. At 31 days postinfection, five additional groups of birds were placed on rations medicated with fenbendazole at 15,30,45,60 or 120 ppm. These latter rations were given ad libitum for 3 consecutive days. One group of turkeys served as an unmedicated, infected control. Treatment group size ranged from 17 to 19 birds. All birds were necropsied 5 days after the medicated rations were withdrawn and nematode recovery was performed. Control birds harbored an average of 3.29 A. dissimilis, 12.06 H. gallinarum, and 65.94 C. obsignata. All but one of the fenbendazole medicated groups showed 100% removal of A. dissimilis. The exception was that group that received fenbendazole at 15 ppm for 6 days, and that showed a 98.5% efficacy. The removal rate for H. gallinarum ranged from 78.6% (15 ppm for 3 days) to 100% (120 ppm for 3 days and 45 ppm for 6 days). The C. obsignata infections proved dose-limiting, with a removal rate ranging from 30.8% (15 ppm for 3 days) to 97.8% (45 ppm for 6 days). PMID- 1924101 TI - Research note: increased growth of chicks and poults obtained from hens injected with jackbean urease. AB - Two experiments were conducted using 120 Single Comb White Leghorn (SCWL) hens and 40 turkey hens. Hens were randomly assigned to two treatments: those injected with urease and controls injected only with adjuvant. At 22 wk of age, half of the SCWL hens were injected intramuscularly with 12 Sumner units of jackbean urease suspended in incomplete adjuvant six times in 26 wk. Turkey hens were injected twice at weekly intervals with 70 Sumner units. The other half of the breeders received adjuvant without urease (control). Urease injection into SCWL hens had no effect on feed consumption, feed conversion, and percentage fertility, hatchability, and hatch of all eggs set, but egg weight and body weight of chicks at hatch and at 3 wk of age were significantly higher as compared with the control hens. In the case of turkey hens, percentage hatchability and progeny body weight were significantly higher as a result of urease injection. PMID- 1924102 TI - Research note: effects of dietary fats on hepatic cholesterol synthesis in Japanese quail. AB - Blood lipid concentrations and hepatic cholesterol synthesis were compared in Japanese quail fed diets containing fats with different fatty acid profiles. The quail fed a diet containing tuna oil had the lowest blood cholesterol concentration; those fed beef drippings the highest, and those fed safflower oil or linseed oil had intermediate concentrations. Rates of hepatic cholesterol synthesis mirrored the results for serum cholesterol concentration. Serum triglyceride concentrations were lower in the quail fed the two diets containing n-3 fatty acids in comparison with the beef and safflower treatment groups. PMID- 1924103 TI - The sexual and contraceptive socialization of black adolescent males (black adolescent sexuality). AB - The major source, quantity, and quality of sex and contraceptive information African-American males received as teenagers, and the impact of that information on sexual and contraceptive behavior, were examined among 250 males ranging in age from 12 to 70 years. Mothers were the major sources of sex and birth control information for the adolescent, young adult, and middle adult groups. Fathers and male friends were the second sources most indicated. All of the sample received sex information, and only a small proportion received no birth control information. The amount of sex information received was found to be a significant predictor (P = 0.0018) of the age at first intercourse and the regularity of use of birth control after that. The amount of birth control information received was also a significant predictor (P = 0.0093) of the regularity of use of birth control after the first coitus. Because parents influence their children's behavior through a socialization process, their support of their teenage sons in matters of sexuality and contraception may be of potential value in mitigating the effects of early, unprotected sex. PMID- 1924104 TI - Sociodemographic factors associated with AIDS knowledge in a random sample of university students. AB - A telephone survey was used to assess knowledge of the transmission, prevalence, and infectivity of acquired immunodeficiency syndrome (AIDS), and the safety of casual contact among 214 randomly selected university students. Males were more knowledgeable than females overall (odds ratio [OR], men/women = 4.8). Although most students understood the dangers of unprotected sex and intravenous needle sharing, up to 30% believed some kinds of casual contact (e.g., shared eating utensils) can transmit AIDS. Older students (greater than or equal to 23 yrs) were more knowledgeable than those 17 to 19 years old about the safety of casual contact (OR = 3.8). Students are in need of education programs that stress the ways AIDS is not transmitted. Since most students identified newspapers and television as their main sources of information, these may be effective vehicles for education efforts. PMID- 1924105 TI - Phenomenologic research as a theoretic initiative in community health nursing. AB - Phenomenologic research is a means of developing clarity on the concepts or phenomena that are the focus of community health nursing practice. Phenomenologic methodology is used in a number of disciplines, including nursing. This paper addresses how the researcher identifies the phenomena of interest, decides on the number of participants, gains access to those individuals, collects data, and analyzes and uses the findings. Specifically, community health nurses can use phenomenology to begin to define the concepts perceived to be of primary concern in the practice arena. PMID- 1924106 TI - Home health care: reliability and validity testing of a patient-classification instrument. AB - The purposes of this methodologic, descriptive, correlation study were to assess the reliability and validity of the Easley-Storfjell (ES) patient-classification instrument for home care, and determine to what extent it was useful in a large, hospital-based home health care setting. A model for home health care developed by the investigator was used. Interrater reliability and concurrent validity were established by four nurse-raters using a random sample. Nonparametric bivariate correlational analysis demonstrated that the ES instrument was both reliable and valid at a significant level. In addition, there was agreement between the overall ES category rating and rater frequency of home visits. Intrarater reliability for each of the four nurse-raters on a random sample was at a significant level. The results of this study have important implications for home health care agencies providing care to chronically ill patients. PMID- 1924108 TI - Applying marketing concepts to promote health in vulnerable groups. AB - Public health nurses must have a valid marketing orientation. Two marketing concepts, exchange relationships and channels of distribution and their application for public health nursing practice, have relevance in this context. In spite of the complexities inherent in applying them, they can be used to promote health in at-risk populations. By incorporating these concepts in planning and delivering public health nursing services, it is hoped that the health goals of a larger number of vulnerable individuals can be achieved. PMID- 1924107 TI - A model research design for comprehensive evaluation of a public home health agency. AB - The Mississippi State Department of Health developed a five-stage model to perform an evaluation study of its home health services program. A singular element in the process was the deferral of developing the final research design structure until the second stage of evaluation was completed. Primary areas of investigation included identification of verifiable, nonverifiable, and erroneously believed factors affecting program operations; recommendations for changes that could be made in light of research findings to improve program operations both to deliver services and to maximize program earnings; and elements affecting program performance held in common with other home health programs in Mississippi and in other states. PMID- 1924109 TI - Quality of life in the working environment. PMID- 1924110 TI - Public health nursing education: a call for action. PMID- 1924111 TI - Holistic concepts and the professionalization of public health nursing. AB - The sociology of knowledge provided the conceptual and methodologic basis for this study of the relationship between the philosophic concept of holism and the professionalization of public health nursing. Set in the context of the history of ideas, the discussion examines the various meanings of holism and the circumstances surrounding their adoption, modification, and use in public health nursing. The nursing literature from the late 1800s to the 1980s was analyzed to explicate the pragmatic consequences of holism for public health nursing, and to examine holism's moral value and its part in establishing and extending public health nursing's professional domain. PMID- 1924112 TI - Specialty roles in community health nursing: a national survey of educational needs. AB - This study identified population groups, health conditions, and employment settings considered appropriate for graduate-level community health nursing (CHN) practice and employment, and described the relative importance of each of these areas as assessed by CHN leaders. According to 588 leaders in CHN service and education, (1) the population groups most in need of graduate-prepared CHNs are the elderly, persons of low socioeconomic status, the homeless, adolescents, and the unemployed; and (2) the health conditions most in need of CHN services are AIDS, pregnancy and prenatal problems, low birth weight and infant mortality, stress-related illness, and Alzheimer's and other chronic diseases of the elderly. Among the many employment settings rated as having a great need for CHNs are state and local health departments and home health agencies. The findings provide the direction and justification for developing specialty options within CHN that correspond to these identified and changing needs. This article provides suggestions and possible alternatives for initiating educational change to prepare graduate-level CHNs for these various specialties and for the settings in which the specialties will be applied. PMID- 1924113 TI - Homeless families: rebuilding connections. AB - Young families are the fastest-growing group of homeless people in the United States. Many women have suffered violations of physical and sexual abuse, reduced income through divorce, and discrimination in seeking housing. Families have been disconnected from their homes, an adequate income, health care services, schools, and their families. Selected literature is reviewed to promote understanding and advocacy nursing for this high-risk population. PMID- 1924114 TI - Preventing low birth weight: marketing and volunteer outreach. AB - Low birth weight (LBW) contributes to infant mortality and continues to be a public health concern in the United States. A community-based prenatal program was established to prevent low birth weight through early and continuous prenatal care. Two key dimensions of the program were marketing and the use of volunteer neighborhood outreach workers. This paper explores the role of the program's public health nurses in relation to these dimensions and makes recommendations regarding marketing and use of outreach workers. PMID- 1924115 TI - Antenatal care--a time for review? PMID- 1924117 TI - Management of migraine. PMID- 1924116 TI - A request for homoeopathy. PMID- 1924118 TI - Advances in bulimia nervosa. PMID- 1924119 TI - What is truth in practice? PMID- 1924120 TI - The MRCGP examination. PMID- 1924121 TI - Community HIV--preparing the practice. PMID- 1924122 TI - HIV testing--practical and ethical issues. PMID- 1924123 TI - Balancing primary care. PMID- 1924124 TI - HIV and AIDS. Values and norms. PMID- 1924125 TI - Counselling the HIV-positive patient. PMID- 1924126 TI - HIV and AIDS. Safer sex. PMID- 1924127 TI - Terminal care for people with AIDS. PMID- 1924128 TI - PACT level 3--a tool for audit. PMID- 1924129 TI - Prescribing controlled drugs. PMID- 1924130 TI - Sixth annual meeting and exposition, American Association of Pharmaceutical Scientists. November 17-21, 1991, Washington, D.C. Abstracts. PMID- 1924131 TI - The nasal mucociliary clearance: relevance to nasal drug delivery. AB - Mucociliary clearance is an important physiological defense mechanism of the respiratory tract to protect the body against noxious inhaled materials. This process is responsible for the rapid clearance of nasally administered drugs from the nasal cavity to the nasopharynx, thereby interfering with the absorption of drugs following intranasal application. This review describes the mucociliary system and the methods used for its characterization. Examples are given of the effects of drugs and additives on its functioning. Further, possible approaches are presented for increasing the residence time of drugs in the nasal cavity, thereby improving intranasal drug delivery. PMID- 1924132 TI - Gas chromatographic-mass spectrometric (GC-MS) determination of MDL 72,222 and four metabolites in monkey plasma. AB - MDL 72,222 a potent serotonin antagonist, is being developed for use as an antiemetic drug in cancer chemotherapy. An assay method has been developed for the determination of MDL 72,222 and four metabolites: N-desmethyl-MDL 72,222 (1), 3,5-dichlorobenzoic acid (2), glycine conjugate of 2 (3), and MDL 72,222-N-oxide (4). The method involves liquid-liquid extractions, derivatization with trifluoroacetic anhydride for metabolite 1, methylation with diazomethane for metabolites 2 and 3, reduction with titanous chloride for 4, and detection of each analyte by GC-MS. In this method d3-MDL 72,222, a 3-methyl-5-chlorobenzoate analogue of 1 (5), and 3,4-dichlorobenzoate analogues of 2-4 (6-8) are used as internal standards for the determination of MDL 72,222 and metabolites 1, 2, 3, and 4, respectively. The method is suitable for quantification of MDL 72,222 and the metabolites 1-4 over a concentration range of 1-150, 0.5-75, 1-150, 0.5-75, and 1-150 ng/ml, respectively. The interday precision and accuracy values are within 10% RSD and 92-110%, respectively. The interday precision and accuracy values are within 14% RSD and 87.6-116%, respectively. The method is specific and sensitive for the analysis of MDL 72,222 and four metabolites in monkey plasma. The assay method has been utilized in analyzing pharmacokinetic study samples. PMID- 1924133 TI - Triplet-sensitized photooxygenation of therapeutic retinoids. AB - The triplet-sensitized photooxygenation of retinoic acid in hydroorganic buffer, methyl retinoate in a variety of solvents, and methyl 13-cis-retinoate and etretinate in ethanol has been investigated. By high-performance liquid chromatographic analysis, one major peroxide product was formed from each retinoid substrate under all conditions investigated. The structures of these peroxides have been assigned relying on high-field nuclear magnetic resonance and mass and ultraviolet spectroscopy. While product structures were not influenced, the rate of product formation was found to vary with solvent, substrate, and perhaps the nature of the sensitizer. The retinoid peroxides isolated are stable toward nucleophiles and weakly acidic and basic conditions. Possible reasons for rate variations in the photooxygenations are discussed. PMID- 1924134 TI - Structure-metabolism relationships in the hydrolysis of nicotinate esters by rat liver and brain subcellular fractions. AB - Rat liver and brain subcellular esterase activities toward nicotinic acid esters were studied, under varying conditions, such as pH, organic solvents, protein concentration, duration of incubation, and substrate concentration. Esterases in each subcellular fraction displayed activities that obey Michaelis-Menten kinetics, although subcellular fractions are heterogeneous. The Km values were of the same magnitude, and the Vmax values were lower in microsomes than in cytosol of the liver. Brain activities normalized to protein concentration, were much lower than liver activities, aromatic nicotinates being the best substrates in both tissues. Myelin and brain mitochondria of nerve-ending and neuroglial origin display esterase activity toward phenyl nicotinate. In contrast to brain esterases, liver esterases appear homogeneous, and esterase activities in both tissues react differently to changes in pH. Qualitative and quantitative structure-metabolism relationships are not suggestive of tissue-specific ester hydrolysis. PMID- 1924135 TI - The importance of surface charge in the optimization of antigen-adjuvant interactions. AB - The adsorptive behavior of the recombinant malarial antigens R32tet32, R32NS181 and NS181V20 to aluminum hydroxide and aluminum phosphate gels was studied as a function of pH and buffer ions. The Plasmodium falciparum antigen, R32NS181, and the P. vivax antigen, NS181V20, with isoelectric points (pI) of 5.9 and 5.5, respectively, adsorbed readily to the positively charged boehmite form of aluminum hydroxide gel. These two antigens displayed reversible, linear adsorption behavior in the pH range 5-9, with maximal adsorption observed at the lowest pH studied. The addition of acetate buffer ions had little effect on adsorption, while the presence of phosphate decreased adsorption for R32NS181 and NS181V20 by 25 and 40% respectively. The adsorptive behavior of these two antigens with the negatively charged adjuvant, aluminum phosphate, was markedly decreased. The converse situation was observed with the R32tet32 antigen, whose pI is estimated to be 12.8. There was minimal interaction of this antigen with aluminum hydroxide gel except in the presence of phosphate counter ions and significant, nonreversible adsorption with aluminum phosphate gel. Enhanced adsorption of R32tet32 to aluminum hydroxide gel in the presence of phosphate is suggested to be the result of a covalent bond between a surface aluminum and a phosphate anion that modifies the surface charge of the aluminum hydroxide gel. These results indicate that the role of complementary surface charges, both for the ionization state of the protein and for the aluminum adjuvants, is the key in optimizing conditions for significant antigen-adjuvant interactions. PMID- 1924136 TI - Quantitative evaluation of ethanol effects on diffusion and metabolism of beta estradiol in hairless mouse skin. AB - The influence of low levels of ethanol on the simultaneous diffusion and metabolism of beta-estradiol (E2 beta) in hairless mouse skin was quantitatively evaluated. A wide range of diffusion/metabolism experiments was conducted with full-thickness skin, stripped skin, and dermis at the various ethanol levels. The experiments were carried out in a two-chamber diffusion-cell system where ethanol was present in both the donor and the receiver chambers at equal concentrations. Analysis of the experimental data with several enzyme distribution models further showed that the best model was that for which the enzyme activity resided totally in the epidermis and near the basal layer of the epidermis. The ethanol effects were separated and quantified in terms of the diffusion and metabolism parameters. Aqueous ethanol, even at low concentrations (greater than or equal to 25%), was found to have two important effects on E2 beta transport: ethanol functions as an inhibitor of the enzymatic conversion of E2 beta to estrone (E1) in the viable epidermis, and ethanol is able to enhance the transport of permeants across the lipoidal pathway of the stratum corneum. PMID- 1924137 TI - Enhancement of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor efficacy through administration of a controlled-porosity osmotic pump dosage form. AB - An extended-release osmotic dosage form was designed for gastrointestinal delivery of the water-soluble tromethamine salt of the beta-hydroxyacid form of simvastatin, a potent HMG-CoA reductase inhibitor and cholesterol lowering agent. The cholesterol lowering efficacy and systemic plasma drug levels resulting from peroral administration of this dosage form, relative to a powder-filled capsule oral bolus, were evaluated in dogs. A twofold improvement in cholesterol lowering efficacy was realized with the controlled-release dosage form that was accompanied by a drug AUC and Cmax that were 67 and 16%, respectively, of those achieved with the bolus dosage form. These results suggest that extended-release dosage forms have the potential for a dose-sparing advantage in the administration of HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia. PMID- 1924138 TI - Variable glyceryl dinitrate formation following infusions of glyceryl trinitrate at different vascular sites in the rat. AB - The availability of glyceryl trinitrate (GTN) and the differential formation of dinitrate metabolites (GDNs) in various organs as a function of routes of administration were investigated in the rat. GTN was infused at 2.0 micrograms/min via the left femoral vein (LFV), left external jugular vein (LJV), left femoral artery (LFA), and hepatic portal vein (HPV). Blood concentrations of GTN and GDNs were measured in femoral arterial samples. Different infusions yielded GTN steady-state concentrations in the following rank order: LJV greater than or equal to LFV greater than LFA greater than or equal to HPV. Furthermore, the GDN formation ratios (1,2-GDN/1,3-GDN) are different: LFV greater than LJV greater than LFA greater than HPV. The availabilities of GTN through the leg, vein, and liver were derived. GTN is significantly extracted and metabolized in these organs, and the leg and the vein prefer 1,2-GDN formation, while the liver forms 1,3-GDN predominantly. PMID- 1924139 TI - Steady-state pharmacokinetics and pharmacodynamics of benazeprilat in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. AB - The effects of the simultaneous steady-state intravenous infusion of benazeprilat, the active metabolite of benazepril HCl, and angiotensin I (AI) on mean arterial blood pressure were investigated in the conscious, unrestrained spontaneously hypertensive rat (SHR) and its normotensive parent strain, the Wistar-Kyoto (WKY) rat. A competitive inhibition model is applied and the limits of its validity are discussed. Deviations from the model are apparent at high drug infusion rates and may relate to the effect of benazeprilat on the clearance of AI. The strains differ in the amounts of angiotensin converting enzyme (ACE) or responsiveness to angiotensin II (AII), the drug clearances, and either the pharmacology or the distribution of the drug. Since the latter two differences are drug dependent, prediction between strains is rendered difficult. This steady state approach relates the hypertension in the SHR to the amount of ACE or responsiveness to AII and renal function. PMID- 1924141 TI - The relationship of diastereomer hydrolysis kinetics to shelf-life predictions for cefuroxime axetil. AB - Cefuroxime axetil, an ester prodrug of cefuroxime, is comprised of a 50:50 mixture of diastereomers A and B. The first-order hydrolysis kinetics of cefuroxime axetil were investigated as a function of pH, temperature, buffers, and ionic strength. Chromatographically identified hydrolysis products were cefuroxime, delta 2-cefuroxime axetil, and alpha, beta-sulfoxides. Buffer catalysis was observed in acetate and phosphate buffers. No significant kinetic effect was observed for ionic strength in the range mu = 0.1-1.0. The pH-rate profiles for hydrolysis of cefuroxime axetil isomeric mixture were obtained at 45, 35, and 25 degrees C. The equation defining the cefuroxime axetil hydrolysis rate constant as a function of pH was kobs = kH (aH) + ks + kOH(KW/aH), exhibiting maximal stability in the pH range 3.5 to 5.5. The predicted profile at 5 degrees C was in excellent agreement with experimental data in the pH range 3.6 to 5.5. In the pH range 1 to 9, the maximum difference observed for individual hydrolysis constants of isomers was 27%. Shelf-life estimates based on the hydrolysis rate constants for cefuroxime axetil as an isomeric mixture were shown to be equivalent to those based on individual hydrolysis rate constants for isomers A and B. PMID- 1924140 TI - Binding study of the fluorescence probe 1-anilino-8-naphthalensulfonate to human plasma and human and bovine serum albumin using potentiometric titration. AB - The binding of 1-anilino-8-naphthalenesulfonate (ANS) to bovine serum albumin (BSA), human serum albumin (HSA), and human plasma has been studied by potentiometric titration utilizing a laboratory constructed ion selective electrode (ISE) of ANS. Three classes of ANS binding sites were found on BSA, HSA, and plasma at 25 and 37 degrees C. Computer analysis of the data resulted in estimates for the association constants, number of binding sites (HSA, BSA), and binding capacity of each class. The association constants for the first class of binding sites at 25 degrees C were found to be 7.53 (+/- 0.59) x 10(5), 2.70 (+/- 0.20) x 10(5), and 2.64 (+/- 0.26) x 10(5) M-1 for BSA, HSA, and plasma, respectively. Lower values for the association constants of all binding classes were estimated at the higher temperature (37 degrees C). The binding capacity for ANS decreased in the order BSA, plasma, HSA. PMID- 1924142 TI - A simple and rapid method for the quantification of Eudragit RS100 and RL100 poly(methacrylates) in sustained-release dosage forms. AB - A colorimetric ion-pair complexation method has been developed which provides a simple and rapid way of quantifying Eudragit RS100 and RL100 in pharmaceutical dosage forms. The quaternary ammonium groupings in these polymers appear to form an ion-pair complex with the dye tropaeolin OOO. When extracted into an organic phase, the optical density at 484 nm is linearly related to polymer concentration. Control of pH is important, and it should be maintained within the range 4.5 to 9.0. A wide range of pharmaceutical excipients commonly used in tablet, pellet, and film-coating formulations did not interfere with formation of the complex, but certain drugs were found to significantly enhance or decrease the assay response. Good reproducibility, precision, and accuracy were demonstrated when the method was applied to a film-coated pellet formulation containing an interfering drug (promethazine hydrochloride). However, removal of interfering substances must be optimized. The method was sufficiently sensitive for the determination of polymer on a single dose unit of encapsulated beads. PMID- 1924143 TI - An electrically modulated drug delivery device: I. AB - A controlled drug delivery device based on the principle of electrophoresis is described. A model system using propranolol HCl and PHEMA films was used to demonstrate how control over the release of a model drug may be achieved using low constant electric currents. It was found that a linear relationship existed between electric current and drug delivery rate. Additionally, two main effects of applying an electric current during the lag period of delivery from the system were identified. First, the drug delivery rate was less when a current was applied before the lag period had expired, and second, the voltage-time profiles were found to be significantly different. The model shows the feasibility of using an electrophoretically controlled drug delivery device to provide truly controllable and predictable release rates. PMID- 1924144 TI - Tablet formulation study of spray-dried sodium diclofenac enteric-coated microcapsules. AB - Sodium diclofenac enteric-coated microcapsules were prepared by a spray-drying technique with Eudragit L 30D as enteric-coating material. The spray-dried powder, mixed with neocel or flo-starch, or the mixture of neocel and flo-starch (weight ratio, 1:1) was directly compressed into a tablet. The micromeritic properties of the spray-dried powder and the mixed powder for tableting were investigated. The flowability of the spray-dried powder was poor but improved after incorporating the excipients. The release rates of sodium diclofenac from the spray-dried powder, the mixed powder before tableting, and the tablets were determined in 0.1 N HCl solution, pH 6.8, phosphate buffer solution, distilled water, and pH-changed medium. The results indicated that the spray-dried powder, the mixed powder before tableting, and the tablets all exhibited enteric-coated release properties; these powders and tablets showed some resistance to stimulated gastric acid and then released drug more rapidly in pH 6.8 buffer solution. The weight ratio of neocel to flo-starch plays an important role in controlling the release of sodium diclofenac from enteric tablets. The 1:1 weight ratio of neocel to flo-starch was more suitable for designing the microdispersed sodium diclofenac enteric-coated tablets. PMID- 1924145 TI - Insulin aggregation in aqueous media and its effect on alpha-chymotrypsin mediated proteolytic degradation. AB - Self-association of zinc-insulin monomers into dimers and hexamers may lead to enhanced protection of the peptide from proteolytic degradation. The present study has been undertaken to investigate the relationship, if any, between the rate of enzymatic degradation of insulin by a protease, alpha-chymotrypsin, and the extent of insulin aggregation in aqueous solutions. Insulin solutions (0.6 mg/ml) containing varying proportions of dimer and hexamer were obtained by adding ethylene diamine tetraacetic acid (EDTA) within a concentration range of 0.005 to 0.040 mM. As the EDTA concentration was increased above 0.040 mM, a complete dissociation of hexamers to dimers occurred and the rate of enzymatic degradation reached its maximum. The overall first-order rate constants appeared to be linearly related to the square of EDTA concentrations. The apparent first order rate constants for dimer and hexamer degradation obtained from a linear plot of rate constant versus EDTA squared concentration were found to be 0.02800 +/- 0.00065 and 0.00798 +/- 0.00075 min-1, respectively. Two major insulin degradation products were also detected and the kinetics of product appearance agreed well with the disappearance kinetics of insulin. The results indicated that the degradation of insulin dimers by alpha-chymotrypsin is about 3.5 times faster than the degradation of the hexamer. The second-order dependency of degradation rate on EDTA concentration might be due to the fact that insulin hexamers contain two zinc ions which are sequestered by two EDTA molecules. Chelation of zinc ions by EDTA lead to hexamer deaggregation to dimers as was evidenced from a circular dichroism study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1924146 TI - Pharmacodynamics and biophasic drug levels of methionine enkephalin. AB - Methionine enkephalin (Met-E) is a naturally occurring pentapeptide. It appears to mediate pain perception by blocking CNS pathways. Using rabbits, a log dose relationship was obtained between Met-E-induced dilation of the pupil (mydriasis) and constant intravenous infusion dose rates (14, 20, 28, 37, 56, 73, and 129 micrograms/min/kg). Steady-state dilation is reached within 9 min. Dose-effect curves (DEC) were fitted by a linear regression analysis of the log dose versus percentage dilation plots. Fitted DEC were used to determine temporal profiles for the relative biophasic drug level. PMID- 1924147 TI - Dodecyl N,N-dimethylamino acetate and azone enhance drug penetration across human, snake, and rabbit skin. AB - The effectiveness of the penetration enhancers, dodecyl N,N-dimethylamino acetate (DDAA) and Azone, on pretreated human epidermis for the permeation of model drugs, indomethacin, 5-fluorouracil, and propranolol-HCl, was studied in in vitro diffusion cells. Snakeskin (Elaphe obsoleta) and rabbit pinna skin were compared as possible models for human skin. The drug concentrations were analyzed by HPLC. With all skins and all model drugs, DDAA increased drug permeability at least as well as Azone, and in most cases it was a more effective permeation enhancer. The relative permeation improvements in human skin, snakeskin, and rabbit skin were 10- to 20-, 5- to 50-, and 20- to 120-fold, respectively. Tritiated water served as an indicator of skin condition. Its penetration in the skin samples was independent of the drugs used, and both penetration enhancers significantly increased the flux of tritiated water through all skins. Thus, DDAA and Azone significantly increased the permeation of lipophilic and hydrophilic model compounds. Rabbit pinna skin was a poor model for human skin in vitro, while snakeskin was much closer to human skin in terms of transdermal permeability. In most cases drug permeability decreased in the order rabbit much greater than human greater than or less than snake. PMID- 1924148 TI - Cotransport of estradiol and ethanol through human skin in vitro: understanding the permeant/enhancer flux relationship. AB - The thermodynamic and kinetic limits of ethanol-enhanced estradiol skin transport have been investigated by studying the relationship between estradiol and ethanol steady-state flux in the cotransport of permeant and enhancer in situations in which there exists an enhancer solvent gradient across the skin ("asymmetric" configuration). For aqueous ethanol solution saturated with estradiol, the flux of estradiol across the human epidermal membrane is empirically observed to be linear with the ethanol flux. A physical model approach has been used to determine the basis of this empirical linearity and to predict permeant/enhancer transport across the skin for the asymmetric configuration. Enhancement factors, determined with a balanced ethanol concentration across the skin ("symmetric" configurations), are used to predict fluxes in the asymmetric configurations. The model demonstrates that ethanol enhances the stratum corneum transport of estradiol and of itself by increasing the respective diffusion coefficients at lower concentrations (less than 50%) and by both increasing the diffusion coefficients and decreasing the membrane activity coefficients at moderate concentrations (50 to 75%). The model also demonstrates that the permeant flux, in general, is not linear with the cotransported enhancer flux. PMID- 1924150 TI - Structural effects on the binding of amine drugs with the diphenylmethyl functionality to cyclodextrins. I. A microcalorimetric study. AB - Solution calorimetry has been employed to evaluate the stability constants and enthalpy changes associated with complex formation between alpha-, beta, or gamma cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. Data from thermal titrations of the compounds were analyzed using nonlinear least squares. The standard free energy decrease accompanying the formation of inclusion complexes is generally due to a negative standard enthalpy change (delta H degrees). The standard entropy change (delta S degrees) was negative, except in the case of complexes formed with gamma-CD. Of the 13 compounds studied, only 2 formed complexes with 1:2 (compound:beta-CD) stoichiometry, terfenadine . HCl and cinnarizine . 2HCl. All the others formed 1:1 complexes. The structural effect on the stability constants, thermodynamics, and inclusion geometry was explored by relating the calorimetric results to the chemical structures of the guest molecules and the cavity sizes of the CD molecules. The results suggest that one of the phenyl groups of the diphenylmethyl functionality resides in the CD cavity and is in van der Waals contact with the inside wall of the CD cavity. In the case of alpha- and beta CDs, van der Waals interaction dominates in the stabilization. On the other hand, the interaction between these compounds and gamma-CD is largely entropically driven. Adiphenine . HCl forms a more stable complex with beta-CD than proadifen . HCl, suggesting that hydrogen bonding to the carbonyl oxygen by the hydroxyl group on the rim of the CD ring can influence the strength of the binding interaction. PMID- 1924149 TI - Rectal mucosa damage in rabbits after subchronical application of suppository bases. AB - The effect of suppository bases on rabbit rectal mucosa was investigated using six triglyceride bases, polyethylene glycol, and a triglyceride base combined with monoglycerides or fatty acids and methyl esters of those acids. Rectal irritation was evaluated and scored according to defined pathological features. "Pure" triglycerides and a triglyceride to which a nonionic surfactant was added caused severe mucosal damage with ulceration and inflammation. Hyperemia was characteristic for irritation by polyethylene glycol suppositories. Mucosal damage by a pure triglyceride combined with monoglycerides or fatty acids and methyl esters of those acids was similar but statistically less pronounced than with all other bases. PMID- 1924151 TI - Controlled delivery of diphtheria toxoid using biodegradable poly(D,L-lactide) microcapsules. AB - Diphtheria toxoid, which is an important vaccine in the expanded program of immunization (EPI) in the developing countries, was microencapsulated using poly(D,L,-lactide) of 49,000 molecular weight and the in-water drying technique. The microcapsules were subjected to an in vitro antigen release study using a sensitive enzyme-linked immunosorbent assay (ELISA) developed in the laboratory. Antibody titers in immunized Balb/C mice were also determined using direct ELISA. The antibody units in the immunized group till day 75 were quite comparable to those in the group receiving conventional three-dose injection of diphtheria toxoid with calcium phosphate as an adjuvant. SEM photographs of the microcapsules during in vitro degradation demonstrated the erosion kinetics of the polymer, leading to controlled release of the antigen. PMID- 1924152 TI - Synthesis of the enantiomers of reduced haloperidol. AB - Reduced haloperidol (RHAL) is the best known metabolite of haloperidol (HAL), having been identified in humans, rats, and guinea pigs. Since RHAL contains an asymmetric center, it can exist in two possible enantiomeric forms. However, the enantiomeric composition of the RHAL formed from HAL in vivo has never been reported. As a first step toward the enantiomeric analysis of biological samples, we have developed an efficient and stereospecific synthesis of (+)- and (-)-RHAL from readily available commercial materials. We have also identified an enantioselective chromatographic method using a chiral HPLC stationary phase which can detect as little as 1% of either enantiomer in synthetic samples of RHAL enantiomers. PMID- 1924153 TI - The solution conformations of lidocaine analogues. AB - IR and 1H NMR studies in CDCl3 and CCl4 of a series of tertiary aminoxylidides with the amino group in the 2 to 6 position of the acyl chain are described. Lidocaine, diethylaminoaceto-2',6'-xylidide, forms an intramolecular five membered ring hydrogen-bonded monomer at all concentrations in both solvents. beta-Diethyl-amino-propiono-2',6'-xylidide forms an intramolecular six-membered ring hydrogen-bonded monomer in CDCl3 and CCl4 but a trans intermolecularly associated species is the major form present at high concentrations in CCl4. The longer-chain homologues are mixtures of nonassociated trans and cis monomers at low concentrations but associated trans forms predominate at high concentrations. Evidence for the presence of a hydrogen-bonded seven-membered ring intramolecular monomer in CDCl3 for gamma-diethylaminobutyro-2',6'-xylidide is presented. The relationship between the molecular conformation and the partition coefficient is discussed. PMID- 1924154 TI - The cryopreservation of liposomes. 1. A differential scanning calorimetry study of the thermal behavior of a liposome dispersion containing mannitol during freezing/thawing. AB - The thermal behavior of water in liposome dispersions and in liposome dispersions containing mannitol at subzero temperatures was investigated with differential scanning calorimetry (DSC). The cooling curves from 20 down to -60 degrees C for a liposome dispersion (bilayer composition PL100H/DCP), monitored at cooling rates of 5 and 10 degrees C/min, showed several heat flows related to water crystallization. All lipid-containing dispersions showed water crystallization at temperatures below -40 degrees C. The magnitude of this heat flow strongly depended on the experimental variables. Cooling rate, particle size, lipid concentration, and location and nature of the cryoprotectant all influenced the water crystallization behavior as shown in the DSC cooling curve. Different fractions of water--presumably related to their location in the dispersion--could be distinguished. It is concluded that DSC provides a valuable tool for the detection of changes in the physical state of water in liposome dispersions during freezing/thawing. The insights gained from these DSC studies may make it possible to select--on the basis of rational considerations rather than by trial and error--optimum conditions for the cryopreservation of liposomes containing water-soluble drugs. PMID- 1924155 TI - Biodegradable nanospheres containing phthalocyanines and naphthalocyanines for targeted photodynamic tumor therapy. AB - Preparation methods of cyanoacrylic nanocapsules or nanoparticles containing phthalocyanines and naphthalocyanines are described. Nanocapsules were obtained by interfacial polymerization in an oil-in-water emulsion. Drug encapsulation efficiency depended upon drug concentration, ethanol concentration, and phthalocyanine sulfonation degree and reached 100% in some cases. Nanocapsules size ranged from 150 to 250 nm and varied with phthalocyanine sulfonation degree and pH of the aqueous phase. Nanoparticles were prepared by the addition of monomer to an aqueous phase containing hydrophilic phthalocyanine derivatives. Depending upon the pH, sizes ranged from 10 to 380 nm. Drug binding was between 75 and 80%. These new preparations could prove useful in the photodynamic treatment of tumors. PMID- 1924156 TI - The pharmacokinetics and metabolism of human relaxins in rhesus monkeys. AB - Two forms of chemically synthesized human relaxin (rHlx and hRlx-2) were administered as 88 micrograms/kg intravenous bolus doses to pregnant and nonpregnant rhesus monkeys. No significant differences in pharmacokinetics were observed between pregnant and nonpregnant animals for either form of relaxin; however, clearance of hRlx (3.1-3.4 ml/min/kg) was significantly slower than clearance of hRlx-2 (6.2-6.5 ml/min/kg) in both pregnant and nonpregnant animals. Although the terminal half-lives for hRlx and hRlx-2 were similar (148-157 min), the initial and steady-state volumes of distribution were somewhat larger for hRlx-2 (71-85 and 398-418 ml/kg, respectively) than for hRlx (61-65 and 294-319 ml/kg, respectively). The metabolism of hRlx-2 was also investigated in pregnant and non-pregnant rhesus monkeys after iv bolus (0.44 mg/kg) or 60-min infusion (1.1 mg/kg) administration. Fast atom bombardment mass spectral analysis of the relaxin immunoreactivity isolated from the plasma indicated that hRlx-2 was partially degraded by removal of amino acids from the C terminus of the B chain. The percentage of intact material declined over a 60-min time course. At 60 min post-dose, intact hRlx-2 was approximately 46-64% of the detected material. Degraded forms representing loss of one and four amino acids (hRlx) from the C terminus of the B chain were approximately 11-13 and approximately 19-34% of the detectable material, respectively. PMID- 1924157 TI - Evaluation of mucoadhesive polymers in ocular drug delivery. I. Viscous solutions. AB - The potential of a mucoadhesive polymer as an ophthalmic vehicle is evaluated within the rabbit. Precorneal clearance of a mucoadhesive polymer solution (Carbopol 934P) is compared to that of an equiviscous nonmucoadhesive poly(vinyl alcohol) solution (PVA) and buffer (PBS). The precorneal retention of the Carbopol 934P, as studied by lacrimal dacryoscintigraphy, is shown to be significantly greater (P less than 0.05) than that of PVA, which, in turn, is significantly greater than that of PBS. The effect of the polymer solution on the bioavailability of pilocarpine is subsequently assessed by measuring the relative miotic response intensities produced by a 1% solution of the drug. Carbopol 934P solution produces a significant increase (P less than 0.05) in bioavailability as compared to PVA and PBS. The bioavailability from PVA is significantly greater (P less than 0.05) than that from PBS. Studies evaluating vehicle-drug association indicated no binding of the drug to the polymer. PMID- 1924158 TI - Solubilization and stabilization of a benzylpenicillin chemical delivery system by 2-hydroxypropyl-beta-cyclodextrin. AB - A dihydropyridine----pyridinium salt redox carrier-based chemical delivery system for benzylpenicillin (1) was complexed with 2-hydroxypropyl-beta-cyclodextrin (HPCD). The solubility of the lipophilic 1, which is incompatible with aqueous formulations, was dramatically increased and showed a linear dependency on the HPCD concentration. The degree of incorporation was 20 mg of 1 per g of complex. The stability study of 1 in various pH buffers indicated the base-catalyzed hydrolysis of the acyloxyalkyl linkage and the hydration of the 5,6 double bond of the dihydropyridine as the main degradation processes. The overall loss of 1, which follows first-order kinetics, was not influenced by changes in ionic strength and elimination of oxygen from the reaction medium. The HPCD complex of 1, which has a stability constant of 720-940 M-1, stabilized the chemical delivery system. The influence of the temperature on the stability of 1 is also discussed. PMID- 1924159 TI - Absorptive clearance of carbamazepine and selected metabolites in rabbit intestine. AB - The intestinal permeability of carbamazepine, an antiepileptic drug, was examined as a function of intestinal site (duodenojejunum vs colon). A "through-and through" in situ intestinal perfusion technique was adopted using the rabbit as an animal model. Coperfusion of the 10,11-epoxide and the 10,11-transdihydrodiol metabolites along with carbamazepine allowed for an examination of the effect of lipophilicity on intestinal permeability when molecular weight differences are negligible. Our results showed that carbamazepine is absorbed from rabbit duodenojejunum as well as the colon, which may explain the prolonged absorption behavior observed in humans. Also, the absorptive clearance of compounds having similar molecular weights is dependent not only on the lipophilicity but also on the extent of solvent drag during the course of the perfusion. PMID- 1924160 TI - Pharmacokinetic study of an iridoid glucoside: aucubin. AB - Aucubin, a promising hepatoprotecting iridoid glucoside, was given intravenously (iv), orally (po), intraperitoneally (ip), and hepatoportally (pv) to rats. A linear pharmacokinetic behavior was obtained after iv administation of 400-400 mg/kg of aucubin. The half-life of aucubin in the postdistributive phase (t1/2, beta), total-body plasma clearance (CLt), and volume of distribution (Vdss) were 42.5 min, 7.2 ml/min/kg, and 346.9 ml/kg, respectively, for a 40 mg/kg dose. There was no significant difference in the parameters as a reult of increasing dose. The partition coefficients of aucubin between n-octanol and buffers of pH 3.0-10.0 were low, while 18.5 +/- 1.3% of aucubin in whole blood partitioned into the blood cells. Plasma protein binding of aucubin was only 9%. The bioavailabilites of aucubin after administration at a dose of 100 mg/kg through pv, ip, and po routes were 83.5, 76.8, and 19.3%, respectively. The pH-stability profile indicated rapid degradation of aucubin at pH 1.2, 1.6, and 2.0, with degradation half-lives of 5.1, 5.8, and 14.8 hr, respectively, at 37 degrees C. Therefore, the low oral bioavailability of aucubin may be attributed to pH instability in the gastric fluid, poor GI absorption due to low lipophilicity, and the possible metabolism in the GI mucosa and liver (so called first-pass effect). PMID- 1924161 TI - Does hydration affect intercellular lipid organization in the stratum corneum? PMID- 1924162 TI - Physicochemical stability of nitrofurantoin anhydrate and monohydrate under various temperature and humidity conditions. PMID- 1924163 TI - Disposition of sulfamethazine and N-acetylsulfamethazine in the rat. PMID- 1924164 TI - In vivo percutaneous penetration/absorption, Washington, D.C., May 1989. PMID- 1924165 TI - Comments on "Particle size and content uniformity," by Yalkowsky and Bolton. PMID- 1924166 TI - Physical characterization of pharmaceutical solids. AB - A general review of the methods available for the physical characterization of pharmaceutical solids is presented. The techniques are classified as being on the molecular level (properties capable of being detected in an ensemble of individual molecules), the particulate level (properties which can be detected through the analysis of an ensemble of particles), and the bulk level (properties which can be measured only using a relatively large amount of material). The molecular-level properties discussed are infrared spectroscopy and nuclear magnetic resonance spectrometry, the particulate-level properties discussed are particle morphology, particle size distribution, powder X-ray diffraction, and thermal methods of analysis, and the bulk-level properties discussed are surface area, porosity and pore size distribution, and powder flow characteristics. Full physical characterization of three modifications of lactose (hydrous, anhydrous, and Fast-Flo) is presented to illustrate the type of information which can be obtained using each of the techniques discussed. PMID- 1924167 TI - Spectrophotometric prediction of the dissolution rate of carbamazepine tablets. AB - A near-infrared (IR) spectrophotometer, integrating optics, and parallel-vector supercomputer are employed to develop a mathematical model that predicts the dissolution rate of individual intact tablets from near-IR spectra (r2 = 0.985). Each tablet can be analyzed nondestructively by the spectrophotometer in less than 1 min. The model permits hundreds of near-IR wavelengths to be used in the determination of dissolution rate, leading to increased accuracy. PMID- 1924169 TI - Simultaneous high-performance liquid chromatographic analysis of cefprozil diastereomers in a pharmacokinetic study. AB - Cefprozil, a new oral cephalosporin, consists of a 90:10 cis:trans isomer mixture. Sensitive, specific and reproducible high performance liquid chromatographic methods have been developed for the simultaneous quantification of the two stereoisomers of cefprozil in plasma and urine samples from human and rats. Cephalexin acted as the internal standard. Plasma protein was precipitated with acetonitrile and trichloracetic acid with subsequent extraction of acetonitrile. After vortexing and centrifuging, the aqueous phase was injected onto a reverse phase C8 column. Urine samples were acidified with sodium acetate buffer (pH 3.8) and then directly injected onto a reverse phase C18 column. The detector was set at 280 nm. These methods were applied to determine protein binding of both isomers in human and rat sera, and to perform a pharmacokinetic study in human. Results showed that both isomers bound moderately to serum proteins with no interference by the other isomer. The pharmacokinetic study in human indicated that cefprozil was well absorbed and the cis and trans isomers have similar pharmacokinetics. PMID- 1924168 TI - Predicting fraction dose absorbed in humans using a macroscopic mass balance approach. AB - A theoretical approach for estimating fraction dose absorbed in humans has been developed based on a macroscopic mass balance that incorporates membrane permeability and solubility considerations. The macroscopic mass balance approach (MMBA) is a flow model approach that utilizes fundamental mass transfer theory for estimating the extent of absorption for passively as well as nonpassively absorbed drugs. The mass balance on a tube with steady input and a wall flux of Jw = PwCb results in the following expression for fraction dose absorbed, F: [formula; see text] where the absorption number, An = L/R.Pw/(vz), L and R are the intestinal length and radius, Pw is the unbiased drug wall permeability, (vz) is the axial fluid velocity, C*b = Cb/Co and is the dimensionless bulk or lumen drug concentration, Cb and Co are the bulk and initial drug concentrations, respectively, and z* is the fractional intestinal length and is equal to z/L. Three theoretical cases are considered: (I) Co less than or equal to S, Cm less than or equal to S, (II) Co greater than S, Cm less than or equal to S, and (III) Co greater than S, Cm greater than S, where S is the drug solubility and Cm is the outlet drug concentration. Solving the general steady-state mass balance result for fraction dose absorbed using the mixing tank (MT) and complete radial mixing (CRM) models results in the expressions for the fraction dose absorbed in humans. Two previously published empirical correlations for estimating fraction dose absorbed in humans are discussed and shown to follow as special cases of this theoretical approach. The MMBA is also applied to amoxicillin, a commonly prescribed orally absorbed beta-lactam antibiotic for several doses. The parameters used in the correlation were determined from in situ or in vitro experiments along with a calculated system scaling parameter. The fraction dose absorbed calculated using the MMBA is compared to human amoxicillin pharmacokinetic results from the literature with initial doses approximated to be both above and below its solubility. The results of the MMBA correlation are discussed with respect to the nonpassive absorption mechanism and solubility limitation of amoxicillin. The MMBA is shown to be a fundamental, theoretically based model for estimating fraction dose absorbed in humans from in situ and in vitro parameters from which previously published empirical correlations follow as special cases. PMID- 1924170 TI - Column-switching high-performance liquid chromatography for on-line simultaneous determination and resolution of enantiomers of verapamil and its metabolites. AB - An on-line simultaneous assay for the enantiomers of verapamil (VA) and its three metabolites in plasma was developed with column-switching HPLC. This system consists of an ovomucoid protein chiral stationary phase coupled to an achiral reversed-phase column via a dilution tube and a trapping column. The reversed phase column was used to separate and quantitate VA, its metabolites, and internal standard, without interference from plasma components. Then each of the eluates containing VA and its metabolites was selectively switched into a sampling loop, and the samples were transferred successively to the trapping column after dilution with a new mobile phase. After concentration on the trapping column, each sample was passed to the ovomucoid column, where the enantiomers were resolved and quantitated. The mobile phases for both HPLC columns were independently optimized and the diffusion of the sample during column switching was minimized. This method was shown to be efficient and reliable. PMID- 1924171 TI - An historical perspective on pigment cell biology from the editor. PMID- 1924172 TI - Mutational analysis of the human p53 gene in malignant melanoma. AB - Nine metastatic melanoma cell lines and two melanocyte cell lines were analyzed for point mutations in highly conserved regions of the p53 gene. No mutations were detected in the two melanocytic cell lines and in eight melanoma cell lines. However, a C----T transition at codon 248, resulting in a substitution of tryptophan for arginine, was found in one melanoma cell line. On immunohistochemical staining, only this cell line showed reactivity for mouse monoclonal antibody 1801, which is immunoreactive with human p53 protein. The original paraffin-embedded specimen from which this mutant cell line was established was obtained, and sequence analysis detected the identical mutation in the p53 gene as that seen in the derived cell line. This is the first report indicating point mutations in the p53 gene in malignant melanocytic tissues. PMID- 1924174 TI - Melanocyte growth factor in normal human skin. AB - Normal human skin is shown to contain melanocyte growth factor (MeGF). We found MeGF activity in extracts of both the epidermal portion of skin and the dermal portion. This activity was completely adsorbed onto heparin beads and eluted by 2.5 M NaCl. In addition, the activity of both extracts was completely blocked by antibodies directed against basic fibroblast growth factor (bFGF). It is suggested that melanocytes in epidermis are supported by bFGF-like MeGF in normal human skin. PMID- 1924173 TI - Complete sequence and expression of a cDNA encoding a chicken 115-kDa melanosomal matrix protein. AB - A full-length cDNA clone encoding a 115-kDa melanosomal matrix protein (MMP115) was isolated from a cDNA library constructed from poly(A)+ RNA of the chicken pigmented epithelial cells. Sequence analysis showed that the cDNA encoded a polypeptide of 762 amino acids, including a hydrophobic signal peptide. There are no membrane-spanning regions, but there are five N-linked glycosylation signals. A cysteine- and histidine-rich domain is present near the C-terminus. A sequence of 24 amino acids is repeated three times in the polypeptide. A database search for homologies yielded no sequence similarities in other proteins. A plasmid containing the full-length cDNA was transferred into mouse cell lines by transfection. The transfected cells produced a protein that had the same size, 115 kDa, as the mature MMP115. When B16 mouse melanoma cells were transfected, the chicken MMP115 was expressed in the melanosomes. The presence of a specific sorting signal was suggested for localization of melanosomal proteins. Southern blot analysis has revealed that the homologues of the chicken MMP115 gene are found in many vertebrate genomes. PMID- 1924175 TI - Contributions of the Gordon-Kosswig melanoma system to the present concept of neoplasia. AB - Modern cancerology is based on the oncogene concept. This is rather new. The idea of the oncogene, however, is old, and can be traced back to two sources, namely to "cancer families," reported in 1866 by P. Broka, and to "virus induced" neoplasia, detected by P. Rous in 1911. A gene which is--to my knowledge--the first reported oncogene by definition was detected in the little ornamental Mexican fish Xiphophorus by Myron Gordon, Curt Kosswig, and Georg Haussler in 1928 when they observed the terrible hereditary melanomas that we are now coming to understand and to compare with other kinds of neoplasms in Xiphophorus and in mammals, including humans. Although the Xiphophorus model was always modest in its claims, it has--sometimes too early in its history--contributed many facts to the present concept of neoplasia. PMID- 1924176 TI - Prognosis of fetuses with a cystic hygroma. AB - This paper reports our experience with 55 fetuses identified in utero to have a cystic hygroma. The outcome of fetuses with an isolated cystic hygroma, cystic hygroma with non-immune hydrops, and cystic hygroma with multiple anomalies was evaluated. Approximately two-thirds of karyotypes were aneuploid, and a strong association of septation and aneuploidy existed. Only five cases, four of which had isolated hygromas, came to term and resulted in live births. Two of these involved small non-septated lesions which resolved in utero. PMID- 1924177 TI - Enhancement of amniocyte growth on a precoated surface. AB - This study investigates whether cell-free amniotic fluid facilitates cell attachment to the surface of culture plates and thereby promotes rapid amniocyte growth. Isolated or pooled cell-free amniotic fluid samples at different volumes were added to culture plates. Trypsinized subcultures, grown in Eagle's minimum essential alpha medium supplemented with fetal bovine serum (4-20 per cent), were monitored by cell counts. The results demonstrated growth stimulation on culture plates precoated with amniotic fluid. The minimal time for coating the culture plates was 6 h. Maximal coating was observed after an overnight incubation with 2 3 ml of the fluid per culture vessel. No synergistic effect from addition of fetal bovine serum to amniotic fluid was observed. A freshly coated surface provided the best amniocyte growth. When primary cultures are grown on a precoated surface, there is an increase in colony counts in 80 per cent of the samples tested. This method may be used to improve amniocyte growth, especially in samples with relatively small numbers of cells. PMID- 1924178 TI - Prenatal diagnosis and outcomes of five cases of mosaicism for an isochromosome of 20q. AB - Five cases of mosaicism for an isochromosome of 20q have been detected from a total of 50,000 cases analysed for prenatal diagnosis by amniocentesis. Karyotypes were designated mos 46,X-/46,X-,i(20q). In all cases, the abnormal cell line was detected in more than one primary culture, thus fulfilling the criterion for true (level III) mosaicism. Indications for prenatal diagnosis were parental anxiety (two cases), low maternal serum alpha-fetoprotein (AFP) (two cases), and high maternal serum AFP (one case). Level II ultrasounds on all five fetuses were normal, and the abnormal cell line was never detected in fetal blood and/or cord blood. All five pregnancies were continued and had normal outcomes, with birth weights ranging from 2.4 to 3.8 kg. The development of all five children has been normal, with the oldest child in the study now 4 years of age. We suggest that the abnormal cell line in each case was of extrafetal origin, and that this may be one of the more common examples of this phenomenon, occurring in approximately 1/10,000 prenatal diagnoses. Mosaicism i(20q) may have been missed in the past because of the higher resolution necessary to detect this subtle change. PMID- 1924179 TI - First-trimester prenatal diagnosis of hypophosphatasia: experience with 16 cases. AB - We have carried out first-trimester prenatal diagnosis of hypophosphatasia in 16 pregnancies with a 1 in 4 risk of this condition. The liver/bone/kidney isoenzyme of alkaline phosphatase was measured in chorionic villus samples using a specific monoclonal antibody and an enzymatic amplification system. Fifteen of the 16 pregnancies were correctly predicted, while one has been lost to follow up. We suggest that this assay system is likely to be superior to DNA-base methods for the first-trimester prenatal diagnosis of hypophosphatasia. PMID- 1924180 TI - Mosaic trisomy 17 in amniotic fluid cells not confirmed in the newborn. AB - A case of true fetal mosaicism 46,XY/47,XY, + 17 was diagnosed in amniotic fluid cells. After genetic counselling and unsuccessful periumbilical blood sampling the pregnancy continued to term, and a healthy male infant was born. Lymphocytes of the newborn had a normal karyotype. Follow-up of the child at age 18 months showed normal physical and mental development indicating that the trisomic cell line was restricted most probably to the extra fetal tissue. PMID- 1924181 TI - Is placental mosaicism associated with poor perinatal outcome? AB - In 37 pregnancies with placental mosaicism detected at first-trimester chorionic villus sampling in 2000 pregnancies, two pregnancies (5.4 per cent) ended in a spontaneous abortion at 15 weeks (46,XX 47,XX, + 16) and in a perinatal loss in a term pregnancy (46,XY/47,XY, + 10), respectively. The outcome of the other 35 pregnancies was normal. The total pregnancy loss rate before 28 weeks in the first 1000 pregnancies was previously reported to be 3.6 per cent. PMID- 1924182 TI - Interstitial deletions without phenotypic effect: prenatal diagnosis of a new family and brief review. AB - A 39-year-old woman (G4P1SAB2) was referred for amniocentesis for advanced maternal age. An interstitial deletion of the G-dark band 11p12 was found in the fetus. Blood from the mother and her previous son was cultured and the same deletion was found in both. The absence of phenotypic effect in this family further confirms that G-dark euchromatic deletions are compatible with a normal phenotype, and underlines the importance of checking familial karyotypes even when apparently unbalanced structural rearrangements are found at prenatal diagnosis. PMID- 1924183 TI - Prenatal diagnosis of euchromatic 16p+ heteromorphisms in two unrelated families. PMID- 1924184 TI - Effect of soaking, sprouting, fermentation and cooking on nutrient composition and some anti-nutritional factors of sorghum (Guinesia) seeds. AB - This study was designed to determine the effect of soaking, sprouting, fermentation and cooking on nutrient composition and some antinutritional factors of sorghum seeds (guinesia). Standard assay procedures were adopted to resolve both the nutrients and the antinutritional factors content of the products. Combination of cooking and fermentation improved the nutrient quality and drastically reduced the antinutritional factors to safe levels much greater than any of the other processing methods tested. PMID- 1924185 TI - Quinoa flour in baked products. AB - The performance of quinoa-wheat flour blends (5/95, 10/90, 20/80, 30/70) were evaluated in breads, cakes and cookies. Breads baked with 5% and 10% quinoa flour were of good quality. Loaf volume decreased, crumb grain became more open and the texture slightly harsh at higher usage levels of quinoa flour. A bitter after taste was noted at the 30% level. Cake quality was acceptable with 5% and 10% of quinoa flour. Cake grain became more open and the texture less silky as the level of quinoa substitution increased. Cake taste improved with either 5% or 10% quinoa flour in the blend. Cookie spread and top grain scores decreased with increasing levels of quinoa flour blended with high-spread cookie flour. Flavor improved up to 20% quinoa flour in the blend. Cookie spread and cookie appearance was improved with a quinoa/low-spread flour blend by using 2% lecithin. PMID- 1924187 TI - A simple colorimetric quantification of flavonoids in the flowers of Lonchocarpus cyanescens genus: Lonchocarpus. AB - As part of a continuing study of the Nigerian flora a chemical analysis of the flavonoids of some plants of the family Papilionaceae prominent in traditional medicine was undertaken. The flowers of the selected plants were extracted and the flavonoids were detected and identified by standard methods. In any such biochemical/chemotaxonomic study where a sizeable number of plants are analysed and in which small differences in type and quantity of each sample are critical, a fast and accurate method of determining the composition becomes paramount. In this work, the determination of the concentration of each flavonoid as a factor of absorbance on a simple single cell photoelectric colorimeter (Seagull Electric Institute Model-1) is reported. The results obtained for Lonchocarpus cyanescens genus Lonchocarpus were consistently satisfactory, sensitive and economical compared with the standard thin layer procedure. As far as the authors know, this is the first report of this method in flavonoid work. PMID- 1924186 TI - Seed protein fractions and amino acid composition in gram (Cicer arietinum). AB - Six chickpea strains were analysed for their protein content and various protein fractions. The protein content ranged from 20.9-25.27%. Albumin, globulin, prolamin and glutelin contents ranged from 8.39-12.31%; 53.44-60.29%; 3.12-6.89% and 19.38-24.40% respectively. Salt soluble proteins (albumin + globulin) and globulins resolved into 19-23 bands whereas albumin proteins resolved into 30-34 bands. The molecular weights of various polypeptides ranged from 10-91 kD. Amino acid analysis of total proteins revealed that glutamic acid was present in maximum concentration followed by aspartic acid and arginine. Just like other pulse proteins, chick pea proteins were also found deficient in sulphur containing amino acids. PMID- 1924188 TI - Yield and in vitro nutritional quality of some leguminous seed protein isolates. AB - Seed protein concentrates (SPC) were extracted from 4 leguminous species and the extractabilities of total N (nitrogen), protein N and SPC determined. In addition, composition, calorie value and in vitro enzymatic digestibility of these SPCs was analysed. Results indicate the promising nutritional potential of these SPCs. PMID- 1924189 TI - Utilization of expeller pressed partially defatted peanut cake meal in the preparation of bakery products. AB - Expeller pressed partially defatted peanut cake obtained from skin-free kernels was used as graded supplements in the preparation of breads, sweet buns, cupcakes and yeast-raised doughnuts. Incorporation of cake meal lowered the specific volume and sensory properties, but improved the fresh weight, water holding capacity and protein content of the products. The products containing 10% peanut cake meal were found to be acceptable. PMID- 1924190 TI - Nitrate-nitrite levels in commercially processed and home processed beets and spinach. AB - Nitrate and nitrite content of commercially processed and home processed beets and spinach samples were analyzed using specific ion electrode and colorimetric methods. The home processed beets were found to be significantly higher in nitrate content than the commercially processed beets. This difference was attributed to differences in processing methods. Pickled and Harvard beets contained significantly lower amounts of nitrate/nitrite on a dry weight basis than the other types of processed beets, evidently due to the diluting effect of added sucrose. Home frozen spinach showed a trend toward lower nitrate content than commercially frozen spinach, although the difference was not significant. Length of storage of home processed beets and spinach did not appear to affect nitrate or nitrite content. PMID- 1924191 TI - Influence of spices on utilization of sorghum and chickpea protein. AB - Influence of eight common Indian spices on the protein quality of sorghum and chickpea was studied. Spices used include red chillies (Capsicum annum), black pepper (piper nigrum), coriander seeds (Coriandrum sativum) cumin seeds (Cuminum cyminum), garlic (Allium sativum), asafoetida (Ferula foetida), dry ginger (Zingiber officinale) and ajowan (Carum copticum). Addition of spices did not affect protein digestibility (TD) of sorghum. The BV of all sorghum diets with spices was higher than that of control diet. However, it was significant only in case of diets combined with red chilli + coriander (1:1) mix, black pepper + cumin (1:1) mix, coriander and cumin. Addition of spices did not have any effect on TD or BV of chickpea diets. PMID- 1924192 TI - Mineral composition of some traditional Mexican teas. AB - Teas of plant origin traditionally consumed by the Mountain Pima of Chihuahua, Mexico, were analyzed for mineral nutritional content. Fe, Cu, Zn, Ca, and Mg composition was determined for native teas made from shoots of Tagetes lucida, T. filifolia, Elytraria imbricata, and Holodiscus dumosus, and from root xylem of Ceanothus depressus and Phaseolus ritensis. Native uses of these teas are also described. PMID- 1924194 TI - No accounts of good rapport. PMID- 1924193 TI - Coumarin compounds in cassava diets: 2 health implications of scopoletin in gari. AB - Scopoletin has been isolated and identified in gari, a cassava food consumed in Nigeria (West Africa). Its levels in gari and cassava flour is not altered by post processing treatments such as sundrying, refrigeration and storage. Scopoletin has also been identified as an active principle in the traditional herbal infusion of the fruit of Tetrapleura tetraptera TAUB used in the ethnopharmacology of West Africa. It is a potent hypotensive and non-specific spasmolytic agent. These pharmacological effects of Scopoletin are probably the underlying factors in the slowly developing tropical neuropathy characterised by optic atrophy, nerve deafness and ataxia endemic among populations subsisting on cassava diets such as gari. Hitherto, these toxicities were attributed to cyanogenic glucosides (cyanide) present in cassava. PMID- 1924195 TI - Choosing the best camera system. PMID- 1924197 TI - [Bases of obstructive respiratory tract diseases]. PMID- 1924196 TI - [Asthma as a chronic desquamative eosinophilic bronchitis. Studies on the pathogenetic significance of hypodense eosinophilic granulocytes in bronchial asthma]. PMID- 1924198 TI - [Pathological anatomy in obstructive respiratory tract diseases]. PMID- 1924199 TI - [Esophageal motility disorders, gastroesophageal reflux and obstructive respiratory tract diseases]. PMID- 1924200 TI - [Allergy and obstructive respiratory tract diseases]. PMID- 1924201 TI - [Clinical bases of various forms of obstructive respiratory tract diseases]. PMID- 1924202 TI - [Therapy of obstructive respiratory tract diseases]. PMID- 1924203 TI - [Pulmonary fibrosis and occupational exposure]. PMID- 1924204 TI - [Carcinogens relevant to the bronchopulmonary system]. PMID- 1924205 TI - [Miner's pneumoconiosis: bases, current aspects for prevention, diagnosis and therapy]. PMID- 1924206 TI - [The 1980 ILO classification of pneumoconiosis: experiences and problems]. PMID- 1924207 TI - [Asbestos-induced pleuropulmonary diseases]. PMID- 1924208 TI - [Asbestos-associated lung and pleural diseases--pathological anatomy]. PMID- 1924209 TI - [Occupationally-induced obstructive respiratory tract diseases]. PMID- 1924211 TI - [Roentgenology of pulmonary fibrosis]. PMID- 1924210 TI - [Connective tissue formation in the lungs]. PMID- 1924212 TI - [Etiology of pulmonary fibrosis]. PMID- 1924213 TI - [Lung function in pulmonary fibrosis]. PMID- 1924214 TI - [Clinical aspects of pulmonary fibrosis]. PMID- 1924216 TI - [Morphology of fibrosing lung diseases]. PMID- 1924215 TI - [Alveolitis and pulmonary fibrosis: more current pathogenic and clinical aspects]. PMID- 1924217 TI - [Pulmonary emphysema--introduction to the theme]. PMID- 1924218 TI - [Pathological anatomy of various forms of emphysema]. PMID- 1924219 TI - [Emphysematous lung sclerosis]. PMID- 1924220 TI - [Pulmonary emphysema and environmental factors]. PMID- 1924221 TI - [Lung function diagnosis in emphysema]. PMID- 1924223 TI - [Pulmonary emphysema--research program: possibilities and requirements]. PMID- 1924222 TI - [Alpha-1 proteinase inhibitor substitution: when and how?]. PMID- 1924224 TI - [Clinical aspects of various forms of emphysema--consequences?]. PMID- 1924225 TI - [Long-term results in pulmonary emphysema]. PMID- 1924226 TI - [Bronchial carcinoma: how far should the diagnosis go?]. PMID- 1924227 TI - [Tuberculosis: who is especially at risk today? What are the consequences of infection?]. PMID- 1924228 TI - [Current attempts at identification of mycobacteria]. PMID- 1924229 TI - [The status of tuberculosis in Europe today]. PMID- 1924230 TI - [The course of tuberculosis today]. PMID- 1924231 TI - [Standard therapy of tuberculosis and its variants]. PMID- 1924232 TI - [Clinico-pathological comparisons in tuberculosis among young patients]. AB - Clinico-pathoanatomic features and thanatogenetic aspects in tuberculosis in young subjects have been studied by retrospective analysis of medical documentation and postmortem findings. Among the 43 young subjects who died within 10 years (1979-1988) in 37, tuberculosis was the underlying illness and 18 had two severe diseases. The clinico-pathological features of tuberculosis in young age are now characterized by therapeutic pathomorphism of its most forms, association with other diseases and imposition of iatrogenic complications. These factors should be taken into consideration in the pathogenetic and thanatogenetic assessment of the disease and in the final clinical and pathoanatomic diagnosis. PMID- 1924233 TI - [Setting up a dialogue-automated counselor system for the examination of patients with a phthisio-pulmonological profile]. AB - The Central Research Institute of Tuberculosis of the USSR Ministry of Public Health is engaged in the work for the development of the computed automatized dialogue system--counsel of a physician on questions of the optimization of examination of patients of the ++phthisio-pulmonologic profile under dispensary conditions, which is based on the statistical methods of image discrimination. The system helps in solving tasks of differential diagnosis, diagnostic volume of patients examination and development of recommendations for the further management of patients. PMID- 1924234 TI - [Can we confirm that tuberculosis has been cured?]. PMID- 1924235 TI - [Complex treatment of patients with destructive pulmonary tuberculosis including intramuscular administration of isoniazid]. AB - The results of a complex treatment of 126 patients with destructive pulmonary tuberculosis have been studied. The chemotherapy regimen of 72 patients comprised intramuscular administration of a 10% isoniazid solution and 54 received isoniazid orally. Both groups of patients were identical in the clinical pattern of pulmonary tuberculosis and treatment conditions. Treatment effectiveness proved to be higher in Group I patients in whom the hospital stay was mainly 6 months. With oral isoniazid, it was longer and 24% of patients (versus 9.7% in Group I) required more prolonged therapy. Clinical manifestations, which were identical in both groups in the pre-treatment period, subsided earlier when isoniazid was administered intramuscularly. Hence, intramuscular administration of 10% isoniazid solution, as compared with its oral use, raises the effectiveness of chemotherapy and decreases the terms of a hospital treatment. PMID- 1924236 TI - [Helium-neon laser in the complex treatment of patients with pulmonary tuberculosis]. AB - The paper gives the results of helium-neon laser irradiation of the endobronchus used in the combined treatment of 30 patients with newly-diagnosed pulmonary tuberculosis complicated by nonspecific endobronchitis. Inclusion of endobronchial phototherapy and helium-neon laser radiation in the complex treatment of patients with newly diagnosed pulmonary tuberculosis complicated by nonspecific endobronchitis makes it possible to achieve clinical cure of an inflammatory bronchial process by 35% more frequently and over 2-3 times more rapidly than in its absence and to increase treatment efficiency of the main process; the terms of bacillary excretion decrease by 1 month, on the average, closure of destruction cavities (with an increase in the parameter by 17%) by 1.2 months and hospital treatment by 1.2 months, as compared with the respective parameters obtained by the traditional treatment of the similar patients. PMID- 1924237 TI - [Bacteriostatic activity of blood in patients with pulmonary tuberculosis during polychemotherapy]. AB - Polychemotherapy comprising 4-6 antituberculosis drugs and prescribed either only daily, daily or given on an intermittent basis (every other day) or only on an intermittent basis was given for 4-8 months to 102 patients with destructive pulmonary tuberculosis (in those newly diagnosed, treated earlier and with a process recurrence). Four and, less frequently, three drugs were used per day. Bacteriostatic blood activity (BBA) was high in 90.2% of the patients, at the maximal concentrations, bacteriostasis was seen at 32-256-fold blood dilutions; in 76.4% of the patients BBA persisted at a high or moderate level during 24 hours (blood dilutions were within 1:256-1:8). The maximal and total BBA level was significantly higher in polychemotherapy than in a combination of 3 drugs. In polychemotherapy bacilli excretion was discontinued in 90% and caverns healed in 74.5% of the patients, while in the regimens comprising 3 drugs in the same contingent of patients, similar events occurred in 77% and 60% of the cases, respectively. PMID- 1924239 TI - [Characteristics of chemotherapy of pulmonary tuberculosis and its effectiveness in patients with diabetes mellitus]. AB - Assessment of tolerance to drug preparations and the effectiveness of this therapy in patients with tuberculosis and concurrent diabetes mellitus and with liver abnormality has shown a certain similarity between them, which consists in the fact that these patients were more often given non-conventional combinations of drugs than patients having no combined pathology. The initial regimen of chemotherapy was changed due to a poor tolerance of drug preparations. Prescription of Essentiale in this case to patients with pulmonary tuberculosis and diabetes mellitus is conducive to decline in severity of the adverse reactions to drugs and makes it possible to increase chemotherapy effectiveness. PMID- 1924238 TI - [Effects of salbutamol and aspirin on pulmonary ventilation and hemodynamics in patients with infiltrative tuberculosis]. AB - External respiratory function, central and pulmonary hemodynamics and PaO2 were studied in 30 infiltrative tuberculosis patients in the absence of dissemination signs after a single and course administration of aspirin and inhalation of 2 doses of salbutamol. It was found that aspirin had a potentiating influence on the broncholytic effect of salbutamol and was responsible for the prevention of intrapulmonary shunting in the presence of bronchial dilatation. PMID- 1924240 TI - [Diagnostic possibilities of bone scintigraphy in osteoarticular tuberculosis]. AB - Skeleton scintigraphy with 99mTc-technefor was conducted in 71 patients with bone and joint tuberculosis and in 3 patients with nonspecific spinal diseases. The method was found to be highly sensitive in the diagnosis of a specific process, its localization, dissemination and activity. A correlation was revealed between the quantitative characteristics of isotope accumulation and morphologic signs of tuberculosis activity. Simultaneous visualization of the kidneys made it possible to diagnose their pathology. PMID- 1924241 TI - [Tactics in surgical treatment of combined and complicated forms of active tuberculosis of the spine and lung]. AB - Questions related to surgical treatment of combined forms of active spinal and pulmonary tuberculosis are discussed. The results of conservative and surgical treatment of 14 patients with this pathology were analysed. Tactics of treatment of such patients was established. It was shown that emergency surgery on the spine because of the developing complications can be performed together with intensive antituberculous therapy. PMID- 1924242 TI - [Immunological aspects of pulmonary sarcoidosis]. AB - Some parameters of peripheral blood cellular and humoral immunity were studied in 80 patients with different stages of pulmonary sarcoidosis, which were compared with the results obtained in 30 healthy subjects of the control group. An increase in the total count of lymphocytes, and primarily that of B-lymphocytes, was found, as compared with those in healthy subjects. T-lymphocyte changes were statistically insignificant. The IgM level was found decreased with the values of IgG and IgA being constant, as compared with those in subjects of the control group. In the group of patients there was a statistically significant decrease in the values of total complement with the values of phagocytosis in sarcoidosis patients and healthy subjects being statistically indistinguishable. PMID- 1924243 TI - [Tuberculosis undetected during patient's life]. PMID- 1924244 TI - [Relation between drug intolerance and immunologic disorders in patients with pulmonary tuberculosis]. AB - Data are given on the examination of 128 tuberculosis patients and 30 apparently healthy subjects. The basic parameters of T-cell immunity in tuberculosis patients associated with drug intolerance have been studied. Side effects of chemopreparations arise significantly more often with the initially impaired immunity parameters. A sharp imbalance of basic immune-regulatory T-cell subpopulations was noted prior to the development of clinical manifestations of immunity. The traditionally used methods for relieving drug intolerance fail to normalize T-system parameters. Patients with tuberculin anergy were noted to have an increased tendency to adverse reactions. The findings obtained help in recording the basic mechanisms of drug intolerance formation and development of methods for its prevention and correction. PMID- 1924245 TI - [Immunoregulatory properties of monocytes/macrophages in patients with pulmonary tuberculosis]. AB - Antigen-presenting ability of monocytes/macrophages (Mc/Mph) was studied in 26 patients with pulmonary tuberculosis and in 21 healthy donors. The above investigation has demonstrated that the ability of the Mc/Mph patients to present mycobacterial antigens was not only intact, but also appeared to be even higher than the reference values of Mc/Mph antigen presentation in healthy donors (0.7 and 0.28, respectively). The ability of Mc/Mph to secrete interleukin-1 (IL-1) both spontaneously and as a response to muramil dipeptide, a synthetic macrophage activator, was studied in 24 tuberculosis patients and 15 healthy donors. During the experiment it was revealed that the affected and healthy cells binding to a plastic surface do not differ in their spontaneous production of IL-1 (0.8 and 0.79, respectively). At the same time in response to muramil dipeptide stimulation, the Mc/Mph patients produced lesser IL-1 than those of the healthy donors stimulated under the similar conditions (3.2 +/- 1.1 and 10.6 +/- 3.6, respectively). PMID- 1924246 TI - [Determining the level of malondialdehyde in patients with different types of tuberculous uveitis]. AB - A clinical follow-up of 52 tuberculous uveitis patients showed that the choice of an appropriate plan of pathogenetic treatment and prognosis of the disease outcome requires differentiation of types of a tuberculous process in the eye. A new method has been suggested for determining the type of the tuberculous uveitis course by studying changes in the blood content of malonic dialdehyde (increase, decrease or absence of changes). PMID- 1924247 TI - [Correction of immunologic deficiency in experimental tuberculosis and chronic effect of pesticides]. AB - The paper deals with the findings of comparative morphologic and immunologic studies of immunomodulatory therapy for experimental tuberculosis on chronic exposure to pesticides (alpha-3) of 117 guinea pigs receiving decaris (levamisole), as an immunostimulator, and "mumiyo-acil", as a biostimulator. The specific features of every pathogenetic drug's effect on the tuberculous inflammation morphology, cellular-tissue reactions, cellular immune response and repair processes were defined. An optimum effect in the treatment of the pesticide-induced experimental tuberculosis can be achieved by the use of anti bacterial drugs and "mumiyo-acil". PMID- 1924248 TI - [Ways to improve hospital services for patients with urologic tuberculosis]. PMID- 1924249 TI - [Various aspects of etiopathogenesis od occupational and ecologic allergic diseases of the respiratory organs]. PMID- 1924250 TI - [Organizational measures regarding joint activities of the forensic-medical, anti tuberculosis and sanitary-epidemiological services]. AB - The preventive aspect of work aimed at early detection of infected subjects and pulmonary tuberculosis patients comprises fuller and earlier awareness of antituberculosis dispensaries for all cases of active pulmonary tuberculosis detected at autopsy during a forensic medical examination. Detection of this contingent of patients requires constant contact of forensic medical experts, phthisiologists + and physicians of the sanitary-epidemiologic service and general therapeutic establishments, which will enable a reduction of tuberculosis infection spread and risk of pulmonary tuberculosis contamination. PMID- 1924251 TI - Species identification and characterization of an Acanthamoeba strain from human cornea. AB - The isoenzyme pattern of an Acanthamoeba, stock H-1, isolated from a patient with keratitis (Krankenhaus Heidberg, Hamburg) was compared with that of two strains of A. quina-A. lugdunensis (302-2, 312-1), two stocks of A. lenticulata (45, 89 1) and one strain of A. rhysodes (302-1). The isolated stock showed glucose-6 phosphate dehydrogenase (G-6-PDH), beta-hydroxybutyric dehydrogenase (beta-HBDH), alcohol dehydrogenase (ADH) and superoxide dismutase (SOD) isoenzyme patterns similar to those of A. quina-A. lugdunensis but their acid phosphatase (AP) patterns differed. Furthermore, cyst morphology showed that the patient-isolated stock belongs to group II of the taxonomic classification of Acanthamoeba. This stock was not thermophilic and exhibited non-pathogenic properties after its intranasal instillation into NMRI mice, whereas it killed BALB/c mice. Immunofluorescent studies revealed the presence of antibodies against Acanthamoeba in the patient's serum. Immunoblotting experiments showed that a 45 kDa protein reacted with this serum. Such an antigen was also detected in A. quina-A. lugdunensis and A. lenticulata. Lectin reactions with Canavalia ensiformis, Ricinus communis-120, Lotus tetragonolobus, Ulex europaeus I, Helix pomatia, Arachis hypogaea, Triticum vulgaris, Glycine maxima, Bauhinia purpurea and Mycoplasma gallisepticum demonstrated that only the A. lenticulata stocks could not be distinguished and that the H-1 stock was more similar to the A. lugdunensis 302-2 strain than to the other acanthamoebae. PMID- 1924252 TI - Lipids and fatty acids of tachyzoites and purified pellicles of Toxoplasma gondii. AB - Various lipids were extracted from tachyzoites and from purified pellicles of Toxoplasma gondii. Extracts from both sources were found to have a low cholesterol/phospholipid ratio. The major phospholipid in these fractions was phosphatidylcholine associated with a low amount of sphingomyelin. Oleic acid represented one-third of whole-cell fatty acids and 44% of pellicular fatty acid content. The lipid composition of the pellicle of T. gondii is consistent with the previously reported high fluidity of this membrane. PMID- 1924253 TI - Effect of the 8-aminoquinoline primaquine on culture-derived gametocytes of the malaria parasite Plasmodium falciparum. AB - Gametocytes from the Honduras I/CDC clone HB-3 of Plasmodium falciparum were exposed to different concentrations of primaquine diphosphate. It could be shown that the drug acts specifically on the mitochondria of the cells by destroying their internal structure and causing these organelles to swell. PMID- 1924254 TI - A simple and efficient method for purifying and quantifying schizonts from Theileria parva-infected cells. AB - An improved method for the purification of Theileria parva schizonts from infected bovine cells is described. The technique is simpler and more rapid than previously described methods and gives rise to greater yields of schizonts with negligible contamination by host-cell components. In addition, a fluorescent staining technique was developed whereby live schizonts purified from infected cells can be enumerated and sorted using the flow cytometer. An assessment of the quality of schizonts prepared according to our method as a source of RNA for the construction of parasite cDNA libraries suggests that RNA derived from these preparations is free of host nucleic acids. PMID- 1924255 TI - Hemocyte production in trematode-infected Lymnaea truncatula. AB - In trematode-infected Lymnaea truncatula, as in other lymnaeids, hemocytes are formed in the connective tissue. Mitoses are found singly in blood vessels or connective tissue or occur in hemocyte nodules, developing along the mantle epithelium or associated with blood sinuses. The so-called hemocyte-producing organ in L. truncatula is not equivalent to that in Biomphalaria glabrata, but rather involves the proximal part of the kidney sac. It has a dual structure: the main part, containing podocytes and broad hemal spaces, is adapted for hemolymph filtration; the apical portion, adhering to the mantle and pericardial epithelia, has a thicker connective-tissue frame in which hemocyte nodules may develop. The role of this region of the kidney in hemocyte formation is discussed. PMID- 1924256 TI - Localization and identification of catecholamines in the nervous system of Diphyllobothrium dendriticum (Cestoda). AB - In the central and peripheral nervous system of larval and adult Diphyllobothrium dendriticum, catecholamines were detected using the glyoxylic acid-induced fluorescence method. High-pressure liquid chromatography (HPLC) analysis revealed the presence of dopa (about 65 ng/g fresh weight) and dopamine (5 ng/g fresh weight). PMID- 1924257 TI - Transmission electron micrograph studies of developing oncospheral envelopes of Fimbriaria fasciolaris (Hymenolepididae). AB - Studies of the ultrastructure of oncospheral envelopes of Fimbriaria fasciolaris in utero using transmission electron microscopy revealed three primary layers: uterine, outer and inner envelopes. A capsule was not found. The uterine envelope surrounds up to 12 oncospheres enclosed by the outer and inner oncospheral envelopes. The secondary envelopes arise during the embryos' development and, in part, are formed in a way different from that described for other Hymenolepididae. A thin, folded shell is a derivative of the embryo and the mother organism. The embryophore and oncospheral "membrane" originate intracellularly from the inner oncospheral envelope. The mode of formation and final shape of the definitive oncospheral envelopes in F. fasciolaris and other Hymenolepididae species as well as their terminology are discussed. PMID- 1924258 TI - Skin the tapeworms before you stain their nervous system! A new method for whole mount immunocytochemistry. AB - A new method for making whole-mount immunocytochemical preparations of thick skinned tapeworms is described. The tough tegument of the worms, which is impermeable to primary and secondary antisera, is removed by placing live worms in distilled water for 5-8 h, during which period the tegument is shed. The worms are thereafter fixed and stained as whole specimens using fluorescence immunocytochemical techniques. Both the main nervous structures and the finest neuronal details are revealed by this technique. Several types of antisera combinations are used. Diphyllobothrium dendriticum and Eubothrium crassum served as model organisms in this study. PMID- 1924259 TI - Drug treatment of experimental Capillaria hepatica infection in mice. AB - This report presents the results obtained using 14 anthelmintic compounds that were tested in experimental white mice of the Swiss-Webster strain for their action against Capilaria hepatica. Four of the drugs effectively prevented deposition of C. hepatica ova in mouse liver. The doses at which these four drugs prevented greater than 99% of egg deposition were: albendazole, 30 mg/kg; febantel, 30 mg/kg; mebendazole, 3.13 mg/kg; and oxfendazole, 12.5 mg/kg. Of these, mebendazole is the only agent for which the application of five daily doses of 3.13 mg/kg lay within the dose range recommended for man. PMID- 1924260 TI - A role for protein kinase C in the production of free oxygen radicals in response to Nippostrongylus brasiliensis. AB - The involvement of protein kinase C in the initiation of free oxygen radical generation by rat leukocytes in response to the nematode Nippostrongylus brasiliensis was investigated. Inhibitors of protein kinase C, trifluoperazine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), inhibited free radical generation in response to N. brasiliensis in vitro. Neither inhibitor affected free radical generation by the cell-free xanthine/xanthine oxidase system, indicating that the agents did not scavenge free radicals; they also failed to affect leukocyte viability. Furthermore, activators of protein kinase C, the calcium ionophore A23187 and the diacylglycerol 1-oleoyl-2-acetyl-rac-glycerol (OAG), enhanced free radical generation by leukocytes in response to N. brasiliensis in vitro. Thus, protein kinase C apparently plays an important role in the initiation of free radical generation in response to N. brasiliensis; since free radicals may play a critical role in worm expulsion, this implies that protein kinase C may also be important in the rejection of N. brasiliensis from the small intestine of the rat. PMID- 1924262 TI - Autoradiographic and morphological investigations on the uptake and incorporation of tritiated lysin by acanthocephalans. AB - Four palaeacanthocephalans and two eoacanthocephalans from fish were autoradiographically investigated for their in vitro uptake of tritiated lysin. All worms took up the labelled amino acid at their surface without showing a species-specific pattern. The tegument of the metasoma was more heavily labelled than the presomal tegument, suggesting that the worms predominantly absorb the nutrient from the food inside the host's gut in vivo. Within the metasomal tegument the nuclei revealed the most intense labelling. In the muscles the outer myogenic belt absorbed more radioactivity than did the enclosed cytoplasmic core. In female worms the ovarian balls and eggs that showed incomplete eggshell formation were highly labelled. In male worms the cement glands showed the most intense labelling of all organs inside the body cavity. We conclude that the investigated acanthocephalans require lysin for protein synthesis and for the coding of protein synthesis in the tegumental nuclei. PMID- 1924261 TI - Morphological demonstration of essential functional changes after in vitro and in vivo transition of infective Onchocerca volvulus to the post-infective stage. AB - Transmission electron microscopic investigation of the morphogenesis of Onchocerca volvulus through the third moult to the post-infective stage revealed essential alterations in various larval organs. Complete rebuilding of surface structures, the reduction of secretory granules in the glandular oesophagus, the unfolding of the intestine, an increase in the number of nerve fibres in the nerve ring and novel sensory papillae were significant findings. Transition from third- to fourth-stage larvae (L4) started as early as 48 h after transfer to vertebrate conditions in vivo in surrogate hosts and in vitro. After a resting period of about 60 h to enable a reduction in gland size and the loosening of the old cuticle and formation of the new one, the larvae started to cast the infective-stage cuticle. Young L4 exhibited a thin, monolayered cuticle and did not rebuild a glandular oesophagus. The body cavity widened, the intestine unfolded and the increased number of microvilli indicated the resumption of metabolic activity. PMID- 1924263 TI - Ultrastructure of oncospheral envelopes of Diorchis elisae (Skrjabin, 1914) Spassky et Frese, 1961 (Cestoda, Hymenolepididae). PMID- 1924264 TI - Protein sequences and data analysis--new concept. PMID- 1924265 TI - The primary structure of xylanase from Thermoascus aurantiacus. AB - The amino acid sequence of xylanase isolated from the culture medium of Thermoascus aurantiacus was determined. It had 269 amino acid residues with an alpha-N-acetyl group at the amino terminus. The structure of blocked N-terminal 11 amino acid tryptic peptide except for acetylalanine was determined by sequence analysis of peptides derived from partial acid hydrolysis and from thermolysin digestion. The blocked N-terminal amino acid was determined as N-acetylalanine by electron ionization mass spectrometry. The sequence comparison of xylanase from T. aurantiacus with the xylanases of alkalophilic Bacillus sp C-125 and Cryptococcus albidus showed 40% similarity. Xylanase from T. aurantiacus had up to 15% similarity with the other two xylanases known. All the five xylanases showed a higher degree of similarity at the level of secondary structure. PMID- 1924266 TI - The N-terminal amino acid sequence of phenol hydroxylase contains a dinucleotide binding sequence motif. AB - The N-terminal sequence of phenol hydroxylase from Trichosporon cutaneum was determined by Edman degradation of the integral protein and of fragments obtained by hydroxylamine cleavage and by digestion with Staphylococcus V8 protease. A continuous sequence of 80 residues from the N terminus was determined: TKYSESYCDV10, LIVGAGPAGL20 MAARVLSEYV30 RQKPDLKVRI40 IDKRSTKVYN50 GQADGLQCRT60 LESLKNLRLA70 DKIXSEXNDM80. A single N-terminal sequence was detected, suggesting two identical subunits in the dimeric enzyme. We suggest the occurrence of an FAD binding site near the N terminus. The C-terminal sequence is -LSTA, as determined by carboxypeptidase digestion. PMID- 1924267 TI - Turkey gizzard caldesmon: complete sequence of a C-terminal thrombic fragment that binds actin, tropomyosin and calmodulin. AB - We have determined, by protein chemistry methods, the complete amino acid sequence of a thrombic fragment, "CaD35", which contains the C-terminal 274 residues of turkey gizzard caldesmon. Residues 1-96 of CaD35 comprise an actin binding subfragment which resembles the tropomyosin-binding segment of troponin T. Residues 111-128 and 255-272 may form basic, amphipathic helices that interact with calmodulin. Residues 251-253 (Ser-Ser-Ser) may be phosphorylated. Chymotryptic CaD35, obtained from chicken gizzard caldesmon, nearly identical in sequence to the turkey gizzard fragment, but contains an additional 32 amino acid residues at its N terminus. PMID- 1924268 TI - Identification of regulatory building blocks in Escherichia coli genome. AB - The nucleotide sequences of extragenic regions in the Escherichia coli genome are statistically analyzed. Sequence elements with high occurrence frequencies are identified; these elements are: (1) extragenic palindromic sequences, which are markedly distinguishable from the already identified repetitive extragenic palindromic sequences; (2) promoter sequences of purine biosynthetic genes; and (3) rho-independent terminator sequences. The repetitious occurrence and extensive sequence similarities suggest that these elements share common evolutionary origins. Copies of one sequence element would have become distributed to various positions on the genome during evolution and have been fixed at locations that provide a selective advantage. The extragenic regions of the E. coli genome seem to consist of various regulatory 'building blocks', similar to a protein which consists of modules or domains. PMID- 1924269 TI - EROP-Moscow: specialized data bank for endogenous regulatory oligopeptides. AB - At present we are familiar with several hundred endogenous oligopeptides involved in the functioning of the nervous, immune and endocrine systems. The information on their structures and functions is contained in a specially created data bank. Data on 865 regulatory oligopeptides with a total of 17,723 amino acid residues have been collected. Most molecules have about 10 amino acid residues, although the range chosen was from 2 to 50. The results obtained permitted us to define the difference between oligo- and polypeptides. PMID- 1924270 TI - Structural classification of endogenous regulatory oligopeptides. AB - Based on the criteria of 50% identity in the amino acid sequence, a new method for grouping endogenous regulatory oligopeptides into structural families is presented. Data from the EROP-Moscow data bank on 579 oligopeptides fitting a preset spectrum of functional activities revealed 73 structural oligopeptide groups, 36 of which were called families. PMID- 1924271 TI - Specificity of the amino acid content of endogenous regulatory oligopeptides. AB - The amino acid residue content of endogenous regulatory oligopeptides possessing a certain spectrum of functional activity has been analyzed. It has been shown that compared to proteins, the oligopeptides contain a greater number of positively charged and cyclic radicals. All 579 oligopeptides contained in the EROP-Moscow data bank with the given spectrum of functional activity have been found to have common physicochemical characteristics. PMID- 1924272 TI - Sequence homology between a beta-galactosidase and some beta-glucosidases. AB - A significant sequence homology was found between a thermostable beta galactosidase from Sulfolobus solfataricus and two beta-glucosidases, respectively, from Caldocellum saccharolyticum and from Agrobacterium sp. These glycosidases appear to form a new protein family, since no homology could be detected with established beta-galactosidase or beta-glucosidase families. PMID- 1924273 TI - Characterization of spinach ferredoxin-thioredoxin reductase. AB - Ferredoxin-thioredoxin reductase (FTR) is an iron-sulfur protein which, in the presence of ferredoxin and thioredoxin, catalyses the activation of photosynthetic enzymes such as fructose-1,6-bisphosphatase, NADP-malate dehydrogenase and several others. The results from amino acid composition and N- and C-terminal sequences show that spinach FTR is composed of two nonidentical subunits (mol.wt. = 17,200: A; 15,500:B) present in equal amounts. Other components (mol. wt. = 16,300 and 14,200) observed in preparations are most likely derived from subunit A losing its amino terminal part. We report the amino acid compositions of the two subunits A and B of FTR including their partial terminal sequences. Subunit A has an additional amino-terminal serine-rich sequence which is phosphorylated. PMID- 1924275 TI - Pathological findings in 2300 consecutive endomyocardial biopsies. AB - Endomyocardial biopsy (EMB) is a valuable diagnostic procedure for rejection surveillance in heart allograft recipients and is widely used for evaluation of native heart disease. However, the spectrum and incidence of diagnoses encountered on a heart failure/cardiac transplant service deserve clarification. Of 2300 consecutive EMBs performed during a 2.5-yr period, 79.9% had been performed for rejection surveillance in heart allograft recipients. Of these, 1281 (69.7%) were negative for rejection; 536 (29.1%) were positive (18.9% mild, 9.7% moderate, 0.5% severe); 21 (1.1%) were not interpretable due to insufficient samples. Endocardial lymphocytic infiltrates ("Quilty" effect) were present in 86 (4.7%), ischemia in 12 (0.7%), myocardial calcification in five (0.3%), foreign body giant cells in two (0.1%), valvular tissue in two (0.1%), and liver tissue in one (0.05%). Of the 20.1% of EMBs performed in patients with native heart disease, 298 (64.5%) were abnormal. A total of 239 (51.7%) had myocyte hypertrophy and/or fibrosis, while 37 (8.0%) had active or ongoing myocarditis, two of which were of the giant cell type. Other diagnoses included anthracycline cardiotoxicity in 11 (2.4%), amyloidosis in five (1.1%), hemochromatosis in two (0.4%), healed infarct in two (0.4%), scleroderma in one (0.2%), and foreign body granuloma in one (0.2%). A total of 159 (34.4%) samples had no diagnostic abnormalities; five (1.1%) were insufficient samples. As the number of EMBs performed grows, pathologists must develop expertise in the detection of morphological features pertaining to various cardiac conditions which may have similar clinical presentations. PMID- 1924274 TI - Atherosclerosis suppression in the left anterior descending coronary artery by the presence of a myocardial bridge: an ultrastructural study. AB - Ultrastructural changes of the left anterior descending coronary artery (LAD) by the presence of myocardial bridge (MB) were studied. In contrast with various atherosclerotic lesions in the intima both proximal to MB and in the whole length of the LAD having no MB, intimal thickness beneath MB was remarkably thin. Neither lipid deposition nor foam cells were present there even in the aged. The intima beneath MB consisted of only normal smooth muscle cells (SMCs) in some layers. Collagen fibrils loosely stuffed among SMCs showed a spiraled appearance. The intima distal to MB was thicker than that beneath MB. Modified SMCs were present along with normal SMCs, and foam cells were intermingled with them. By scanning electron microscopy, endothelial cells proximal to MB were arranged in a pavement-like appearance, and they were polygonal and flat. Endothelial cells beneath MB became spindle-shaped and regularly engorged along the direction of blood flow. Such regularity was lost in endothelial cells distal to MB. These endothelial changes indicate that the intima beneath MB is stressed by high shear and that intima proximal or distal to MB is stressed by low shear. It is, thus, suggested that alteration of hemodynamic factors that arise from contraction of MB greatly affects the evolution of atherosclerosis through the regulation of intimal lipid infiltration within the LAD. PMID- 1924276 TI - Observations concerning the pathogenesis of epithelioid hemangioma (angiolymphoid hyperplasia). AB - Epithelioid hemangioma (EH) is a benign vascular lesion that is characterized by well-formed, capillary-sized vessels lined by histiocytoid or epithelioid endothelial cells and often accompanied by a secondary inflammatory infiltrate. Whether or not these lesions are reactive or neoplastic has been debated and is reflected in the various designations, such as angiolymphoid hyperplasia with eosinophilia (ALHE), pseudopyogenic granuloma, and inflammatory angiomatous nodules. In order to study the pathogenesis of this lesion, 96 examples of EH of superficial and deep soft tissue origin were reviewed, noting the frequency with which these lesions arose adjacent to a damaged vessel and the incidence of antecedent trauma. In 60 cases (63%), an artery or vein was associated with the mass and, in the majority (52 cases), the vessel was damaged, as evidenced by the presence of fibrointimal proliferation, discontinuity of the internal elastic lamina, and/or mural disruption. No evidence of active arteritis was seen in any case. Antecedent trauma was documented in 12 cases and, in one of these, the subsequent formation of an arteriovenous malformation and development of the EH were noted. EH associated with damaged vessels or those in which a preceding history of trauma was available did not differ histologically from cases in which these variables were absent. Our findings suggest that a significant percentage of EH of soft tissue are not neoplastic, but arise on a reactive basis probably secondary to damage and repair of an artery or vein. PMID- 1924277 TI - The impact of mitotic index on predicting outcome in breast carcinoma: a comparison of different counting methods in patients with different lymph node status. AB - In a retrospective review of 76 consecutive cases of female breast cancer with no distant metastases at the time of the original biopsy, we compared how efficiently three different counting methods--mitoses/10,000 cells, mitoses/mm2 of tumor, and mitoses/10 high power fields (x 400)--would discriminate survivors from nonsurvivors 10 years after the original diagnosis. The effect was compared in subgroups of patients with different axillary lymph node status. The conclusions are that: (a) the methodology for counting mitoses is not trivial. Indeed, only mitoses/mm2 of tumor permitted prognostic predictions approaching overall statistical significance, at the exclusion of mitoses/10,000 cells, and mitoses/10 high power fields. (b) In each subgroup based on lymph node status, a low mitotic index in the primary tumor confers a better prognosis than a high mitotic index. (c) When comparing subgroups defined by increasing number of metastatic lymph nodes, one observes a gradually increasing proportion of patients whose primary tumor displays a high mitotic index, thus suggesting that a high mitotic index in the primary tumor predisposes to metastases. (d) A combination of lymph node status and mitotic counts offer a more refined ranking for risk of tumor recurrence than predictions based on lymph node status alone. (e) Although mitotic activity has a measurable impact on disease outcome of a patient population, it is paradoxical that counting mitoses is of disappointing prognostic value as a clinical tool. This is so because the method is not helpful in predicting outcome in those individuals whose disease will evolve contrary to the expectations conferred by their lymph node status. PMID- 1924278 TI - Microvasculature in germinal matrix layer: its relationship to germinal matrix hemorrhage. AB - Microvasculature in the germinal matrix layer (GML) was studied by postmortem microangiography and stereomicroscopic observation on cleared specimens in methyl salicylate. A number of arterioles from penetrating and medullary branches of main cerebral arteries were distributed in the GML, forming a fine network of arterioles anastomosing with each other. Many venules in the GML converged at a few points and drained into subependymal veins. The main converging zone of venules was situated inside the GML close to the border zone of the GML and adjacent cerebral parenchyma. The converging zone coincided with the site of GML hemorrhage. Thus, many factors, including both venous and arterial, appear to influence circulation in the GML; ultimately the converging zones become overloaded and rupture, leading to GML hemorrhage. PMID- 1924279 TI - The incidence and distribution of Mycoplasma fermentans (incognitus strain) in the Chicago AIDS autopsy series: an immunohistochemical study. Chicago Associated Pathologists. AB - Mycoplasma incognitus is a recently described organism that was originally isolated by Shyh-Ching Lo from spleen and Kaposi's sarcoma (KS) tissue of patients with AIDS. The mycoplasm has since been found in selected AIDS autopsy cases in which there were tissues with unexplained areas of necrosis. Mycoplasma incognitus is now known to be closely related to Mycoplasma fermentans. In order to determine the incidence and distribution of M. fermentans/M. incognitus in an unselected series, we performed a retrospective immunohistochemical study of 42 HIV-positive autopsies from the Chicago AIDS autopsy series. One case (2.4%) was found to be positive. The patient was a 27-year-old white male homosexual who had no evidence of Kaposi's sarcoma nor of any other neoplastic disorder and who died of Pneumocystis carinii pneumonia. Antigen was present in the macrophages of the patient's spleen, liver, and bone marrow but was not associated with areas of necrosis. All other tissues sampled from this case (brain, heart, testis, lymph nodes) were negative. In the remaining autopsies, organs of the reticuloendothelial system as well as other randomly selected tissues (e.g., lung, heart, testis, pancreas) were screened and found to be negative. Tissues from several non-AIDS autopsies were also found to be nonreactive for M. fermentans/M. incognitus. We conclude that M. fermentans/M. incognitus is not a common agent found in the Chicago AIDS population; that it may be identified in tissue without morphologic abnormality; and that it is not randomly present in non-AIDS autopsies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1924280 TI - Immunocytochemical identification of Helicobacter pylori in formalin-fixed gastric biopsies. AB - H&E and special histochemical stains are used by most laboratories to identify Helicobacter pylori (H. pylori) in gastric biopsy specimens. However, background staining can complicate recognition of H. pylori and small numbers of organisms may be overlooked. Additionally, histochemical stains do not distinguish H. pylori from other spiral organisms. We investigated two commercially available monoclonal antibodies, one directed against Campylobacter coli and C. jejuni (MAB002) and the other against a Campylobacter species flagellar antigen (MAB001), to evaluate potential use in immunocytochemical examinations of fixed tissues. MAB002 reacted with C. jejuni but not H. pylori organisms. MAB001 labeled C. jejuni as well as H. pylori and, therefore, was used to study 220 gastric biopsies from patients undergoing endoscopy. Acute and/or chronic gastritis was present in 60.5% (133/220) of the biopsies examined. MAB001 positivity was identified in 62.4% (83/133) of the tissues with gastritis. Only 2 of 87 (2.3%) specimens without gastritis demonstrated MAB001 labeling. The resulting immunoreactivity was easily identified, allowing specimens to be screened quickly and accurately. No labeling was seen with the non Helicobacter/Campylobacter bacteria or normal tissues evaluated in this investigation. MAB001 can be used to identify H. pylori in histologically processed tissue and will assist pathologists, clinicians, and researchers studying the distribution and pathogenicity of this organism in humans and animals. PMID- 1924281 TI - Detection of numerical chromosome aberrations using in situ hybridization in paraffin sections of routinely processed bladder cancers. AB - An improved protocol for in situ hybridization (ISH) to routinely processed, paraffin-imbedded tissue sections from transitional bladder carcinoma (TCC) is presented. The protocol to detect numerical chromosome aberrations involved treatment of sections with thiocyanate prior to proteolytic digestion, resulting in reproducible ISH reactions. It was used to explore the influence of nuclear truncation in the detection of numerical chromosome aberrations and the detection of tumor cells among stromal and inflammatory cells, to compare the flow cytometric DNA index with chromosome copy number, and to study chromosome heterogeneity within tumors. For this study, a DNA probe for the chromosome region 1q12 was used. Hybridization of model systems with known chromosome numbers, such as sections of paraffin-embedded lymph nodes, paraffin-embedded human peripheral lymphocytes, T24 and Molt-4 cells with two, three, and four chromosomes 1, respectively, showed in at least 50% of the cells the proper number of chromosome hybridization signals in standard 6-microns-thick sections. Depending on the size of the nucleus, a certain percentage of the cells showed lower copy numbers as a result of truncation. In four cases of normal urothelium in paraffin sections, the percentage of nuclei with more than two chromosome spots did not exceed 5%. Comparison of the number of ISH signals, as detected in ethanol-fixed single cell suspensions of 11 TCCs [five flow cytometric (FCM) diploid, three FCM aneuploid, and three FCM tetraploid], with ISH results obtained in paraffin sections of the same tumors showed that typical numerical chromosome aberrations, such as trisomy and tetrasomy up to nonasomy, could be detected. However, the real chromosome copy number is underestimated, especially in tumors with high copy numbers, as detected in the single cell suspensions of the same tumors. Hybridization of a TCC with extremely large nuclei (DNA index = 3.2) containing six to nine ISH signals as detected in the isolated tumor cells, showed that an indication of these real chromosome copy numbers could be obtained in 6-microns paraffin sections. The accuracy for the detection of the chromosome copy number was even higher in cases where hybridization signals were counted in the mitotic cells. Furthermore, chromosome heterogeneity was detected by ISH using centromeric probes for chromosomes 7, 9, and 18, even though nuclei are truncated in the section. The surplus value of ISH on paraffin sections, as compared with ISH on isolated tumor cells, can be summarized as follows. (a) The focal tumor cell areas with chromosome aberrations can be recognized in the sections and be correlated with the histologic appearance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1924282 TI - Amyloid and amyloidoses: differences, common themes, and practical considerations. AB - Amyloidosis is not one entity but a grouping of disorders in all of which there is a tissue protein deposit with similar morphological, structural, and staining properties despite involving fundamentally different proteins or peptides. Each protein is involved in its own specific pathogenetic mechanism. These mechanisms determine, in a manner as yet unknown, which protein will be present in an amyloid deposit. The role of proteolysis in the pathogenesis is questioned. Proteolysis may well be a postfibrillogenic event. Local tissue factors, such as the basement membrane form of heparan sulfate proteoglycan, in addition to perhaps other basement membrane components, may play an important role in the genesis of amyloid. Differences, common themes, and various unanswered questions related to the pathogenesis of the amyloids are presented as are practical diagnostic considerations. PMID- 1924283 TI - Glioneurofibroma: renaming the pediatric "gliofibroma": a neoplasm composed of Schwann cells and astrocytes. AB - Three children had central nervous system tumors with histologic and ultrastructural features corresponding to those of tumors previously described as "gliofibromas." These features, which include a composite appearance with glial and mesenchymal elements, with glial fibrillary acidic protein (GFAP)-containing and GFAP-immunonegative cells, diffuse S-100 immunoreactivity, and basal lamina wrapping processes of both cell types, suggest that the "mesenchymal" cells are Schwann cells, not fibroblasts. We therefore propose to rename this entity "glioneurofibroma." The clinical behavior of these lesions is uncertain but is more often indolent or benign. PMID- 1924285 TI - Familial renal disease. PMID- 1924284 TI - T-cell lymphoblastic leukemia/lymphoma presenting in a recurrent thymoma. AB - A lymphoblastic malignancy presented as the lymphoid component of a recurrent invasive lymphocyte-rich thymoma that had been previously resected and treated with chemotherapy. This high grade lymphoid neoplasm concurrently involved mediastinal nodes and subsequently disseminated to pleural fluid and peripheral blood. Lymphocytes with convoluted nuclei demonstrated a T-lymphoblastic phenotype (UCHL1+, Leu-22+, TdT+) by immunohistochemical studies. T-cell lymphoblastic leukemia/lymphomas in this clinical setting have not been reported, and this case suggests that neoplastic transformation of lymphocytes may occur in longstanding refractory thymomas. PMID- 1924286 TI - Mechanism of synergistic transcriptional transactivation by the human glucocorticoid receptor. AB - Induction of transcription from a promoter with two upstream glucocorticoid response elements is 10- to 20-fold greater than that from a similar promoter with only one response element. We have shown that interactions involving the major transactivation domain of the glucocorticoid receptor (tau 1) are the sole determinant of such synergistic transactivation by the receptor. The other transactivation domain of the receptor (tau 2) did not mediate synergistic transactivation, and therefore the ability to synergize is operationally distinct from the transactivation function per se. The level of synergistic transactivation observed in vivo can be accounted for by the level of cooperative DNA binding seen in vitro for a glucocorticoid receptor derivative containing only the tau 1 and DNA-binding domains. Cooperative DNA binding was also observed using a tau 1-DNA-binding domain protein, which was expressed in Escherichia coli and extensively purified. Therefore, it is likely that direct protein-protein interactions between tau 1 domains mediate the cooperative DNA binding. The role of cooperative DNA binding for synergistic transactivation in vivo is discussed in relation to other possible mechanisms. PMID- 1924287 TI - Ultraviolet irradiation of DNA complexed with alpha/beta-type small, acid-soluble proteins from spores of Bacillus or Clostridium species makes spore photoproduct but not thymine dimers. AB - UV irradiation of complexes of DNA and an alpha/beta-type small, acid-soluble protein (SASP) from Bacillus subtilis spores gave decreasing amounts of pyrimidine dimers and increasing amounts of spore photoproduct as the SASP/DNA ratio was increased. The yields of pyrimidine dimers and spore photoproduct were less than 0.2% and 8% of total thymine, respectively, when DNA saturated with SASP was irradiated at 254 nm with 30 kJ/m2; in the absence of SASP the yields were reversed-4.5% and 0.3%, respectively. Complexes of DNA with alpha/beta-type SASP from Bacillus cereus, Bacillus megaterium, or Clostridium bifermentans spores also gave spore photoproduct upon UV irradiation. However, incubation of these SASPs with DNA under conditions preventing complex formation or use of mutant SASPs that do not form complexes did not affect the photoproducts formed in vitro. These results suggest that the UV photochemistry of bacterial spore DNA in vivo is due to the binding of alpha/beta-type SASP, a binding that is known to cause a change in DNA conformation in vitro from the B form to the A form. The yields of spore photoproduct in vitro were significantly lower than in vivo, perhaps because of the presence of substances other than SASP in spores. It is suggested that as these factors diffuse out in the first minutes of spore germination, spore photoproduct yields become similar to those observed for irradiation of SASP/DNA complexes in vitro. PMID- 1924288 TI - E1BF is an essential RNA polymerase I transcription factor with an intrinsic protein kinase activity that can modulate rRNA gene transcription. AB - We previously described the purification and characterization of E1BF, a rat rRNA gene core promoter-binding factor that consists of two polypeptides of 89 and 79 kDa. When this factor was incubated in the absence of any exogenous protein kinase under conditions optimal for protein phosphorylation, the 79-kDa polypeptide of E1BF was selectively phosphorylated. The labeled phosphate could be removed from the E1BF polypeptide by treatment with calf intestinal alkaline phosphatase or potato acid phosphatase. Elution of the protein from the E1BF promoter complex formed in an electrophoretic mobility-shift assay followed by incubation of the concentrated eluent with [gamma-32P] ATP resulted in the selective labeling of the 79-kDa band. The E1BF-associated protein kinase did not phosphorylate casein or histone H1. Fraction DE-B, a preparation containing RNA polymerase I and all polymerase I transcription factors (including E1BF), lost polymerase I transcriptional activity when treated with phosphatase. The phosphatase-induced inactivation of polymerase I activity associated with fraction DE-B could be reversed by the addition of purified E1BF. Treatment of purified E1BF with heat, SDS, or an ATP affinity analog eliminated its capacity to reactivate dephosphorylated fraction DE-B. These data demonstrate that (i) polymerase I promoter-binding factor E1BF contains an intrinsic substrate specific protein kinase and (ii) E1BF is an essential polymerase I transcription factor that can modulate rRNA gene transcription by protein phosphorylation. Further, these studies have provided a direct means to identify a protein kinase or any other enzyme that can interact with a specific DNA sequence. PMID- 1924289 TI - Moesin: a member of the protein 4.1-talin-ezrin family of proteins. AB - Moesin (membrane-organizing extension spike protein, pronounced mo ez in) has previously been isolated from bovine uterus and characterized as a possible receptor protein for heparan sulfate. We now have cloned and sequenced its complete cDNA, which represents a single 4.2-kilobase mRNA encoding a protein of 577 amino acids. It contains no apparent signal peptide or transmembrane domain. In addition, the protein shows significant sequence identity (72%) to ezrin (cytovillin, p81), as well as similarity to protein 4.1 and talin. All of the latter proteins have been postulated to serve as structural links between the plasma membrane and the cytoskeleton. A similar role for moesin is implied by structure and domain predictions derived from the cDNA-deduced peptide sequence. Furthermore, our data indicate that moesin is identical to the 77-kDa band that copurifies with ezrin in its isolation from human placenta [Bretscher, A. (1989) J. Cell Biol. 108, 921-930]. PMID- 1924290 TI - Physical map of human Xq27-qter: localizing the region of the fragile X mutation. AB - We describe a physical map of the end of the long arm of the human X chromosome encompassing the region from Xq27.2 to the q telomere, inclusive of the chromosomal band Xq28. This region is of particular interest, since it contains the highest density of genes associated with genetic diseases. The map covers a total of 12 megabases (Mb) of DNA and extends from the telomere to 3 Mb beyond the most likely position of the fragile X mutation, defined by a cluster of translocation breakpoints in somatic cell hybrids. The map determines order and position of loci throughout the Xq28 region and localizes cell line breakpoints marking the fragile X region to an interval of 300-700 kilobases between 8 and 8.7 Mb proximal of the Xq telomere. PMID- 1924291 TI - Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis. AB - To date it has been difficult to characterize completely a genetic disorder, such as hemophilia A, in which the involved gene is large and unrelated affected individuals have different mutations, most of which are point mutations. Toward this end, we analyzed the DNA of 29 patients with mild-to-moderate hemophilia A in which the causative mutation is likely to be a missense mutation. Using computer analysis, we determined the melting properties of factor VIII gene sequences to design primer sets for PCR amplification and subsequent denaturing gradient gel electrophoresis (DGGE). A total of 45 primer sets was chosen to amplify 99% of the coding region of the gene and 41 of 50 splice junctions. To facilitate detection of point mutations, we mixed DNA from two male patients, and both homoduplexes and heteroduplexes were analyzed. With these 45 primer sets, 26 DNAs containing previously identified point mutations in the factor VIII gene were studied, and all 26 mutations were easily distinguishable from normal. After analyzing the 29 patients with unknown mutations, we identified the disease producing mutation in 25 (86%). Two polymorphisms and two rare normal variants were also found. Therefore, DGGE after computer analysis is a powerful method for nearly complete characterization of disease-producing mutations and polymorphisms in large genes such as that for factor VIII. PMID- 1924292 TI - Expression of biologically active heterodimeric bovine follicle-stimulating hormone in milk of transgenic mice. AB - Follicle-stimulating hormone (FSH; follitropin) is a pituitary glycoprotein composed of two post-translationally modified subunits, which must properly assemble to be biologically active. FSH has been difficult to purify and to obtain in quantities sufficient for detailed biochemical studies. We have targeted FSH expression to the mammary gland of transgenic mice by using cDNAs encoding the bovine alpha and FSH beta subunits and a modified rat beta-casein gene-based expression system. Lines of bigenic mice expressing both subunits have been generated either by coinjection of the subunit transgenes or by mating mice that acquired and expressed transgenes encoding an individual subunit. Up to 60 international units (15 micrograms) of biologically active FSH per ml was detected in the milk of the bigenic mice. These lines provide a model system for studying the post-transcriptional mechanisms that effect the expression and secretion of this heterodimeric hormone. PMID- 1924293 TI - Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10. AB - Glutamic acid decarboxylase (GAD; glutamate decarboxylase, L-glutamate 1-carboxy lyase, EC 4.1.1.15), which catalyzes formation of gamma-aminobutyric acid from L glutamic acid, is detectable in different isoforms with distinct electrophoretic and kinetic characteristics. GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent diabetes mellitus. Despite the differing GAD isoforms, only one type of GAD cDNA (GAD-1), localized to a syntenic region of chromosome 2, has been isolated from rat, mouse, and cat. Using sequence information from GAD-1 to screen a human pancreatic islet cDNA library, we describe the isolation of an additional GAD cDNA (GAD-2), which was mapped to the short arm of human chromosome 10. Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different from that detected by GAD-1. GAD-2 recognizes a 5.6-kilobase transcript in both islets and brain, in contrast to GAD-1, which detects a 3.7-kilobase transcript in brain only. The deduced 585-amino acid sequence coded for by GAD-2 shows less than 65% identity to previously published, highly conserved GAD-1 brain sequences, which show greater than 96% deduced amino acid sequence homology among the three species. The function of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined. PMID- 1924294 TI - Haplotypes of the steroid 21-hydroxylase gene region encoding mild steroid 21 hydroxylase deficiency. AB - Haplotypes of the complement 4 (C4) and steroid 21-hydroxylase [21-OHase; steroid hydrogen-donor: oxygen oxidoreductase (21-hydroxylating), EC 1.14.99.10] repeated gene complex were studied in nine families with at least one member affected with a mild form of 21-OHase deficiency. DNA probes from different parts of the repeated C4/21-OHase unit were used to follow the segregation of hybridization patterns in the families. Ten structurally distinct haplotypes of the C4/21-OHase gene region were identified, and the encoded phenotype was assigned to 34 of the 36 C4/21-OHase haplotypes. Four structurally different haplotypes with three C4/21-OHase repeat units were found. Eight of the nine haplotypes found with triplications of the C4/21-OHase repeat unit encoded the mild form of 21-OHase deficiency, whereas one particular triplicated haplotype encoded a severe form of the disease. In one case the mild form of 21-OHase deficiency was encoded by a haplotype with a single C4/21-OHase repeat unit. Mild 21-OHase deficiency was predicted in a patient by the presence of a triplicated haplotype. The finding of deranged 21-OHase genes on all triplicated C4/21-OHase haplotypes indicate that most of these common haplotypes carry mutated 21-OHase genes, and thus may cause functional polymorphism of general importance in the population. PMID- 1924296 TI - The position of the microtubule-organizing center in directionally migrating fibroblasts depends on the nature of the substratum. AB - Immunofluorescence and confocal microscopy were used to monitor the positioning of microtubule-organizing centers (MTOCs) during directional migration of chicken embryo fibroblasts on planar substrata and within three-dimensional collagen gels. Homologous assay conditions based on the radial emigration of cells from cell aggregates were used in both cases. Whereas approximately 70% of the cells migrating directionally on glass and at least 60% on other planar substrata have their MTOCs anterior to the nucleus, MTOCs are randomly distributed around the nucleus in cells within collagen gels. The anterior location of the MTOC in cells on glass is attained gradually during the first 4 hr of directional migration. Cells on oriented planar substrata, manufactured by photolithographic etching of narrow parallel grooves into the glass surface, also have a random position of the MTOC, although the cells themselves assume a highly polarized cell shape parallel to the grooves. This environment mimics the partial orientation of the collagen fibers produced by the tractive forces of the cells within collagen networks. These findings demonstrate a difference in MTOC positioning between fibroblasts on planar substrata and within a quasinatural environment. PMID- 1924295 TI - Effects of injected Alzheimer beta-amyloid cores in rat brain. AB - Although amyloid deposits have long been known to accumulate in Alzheimer disease (AD) brain, their origin and significance remain speculative. Because of the lack of an in vivo model where amyloid deposits can be induced, the relationship of the extracellular beta-amyloid deposits to other AD pathology has never been directly investigated. Therefore, we injected SDS-isolated amyloid cores into rat cortex and hippocampus. Similarly isolated lipofuscin fractions from control human brains were injected on the contralateral side. Rats were perfused and brains were examined immunohistochemically at 2 days, 7 days, and 1 month after injection. Alz-50, a monoclonal antibody against abnormally phosphorylated tau proteins, stained neurons along the cortical needle track at 2 but not 7 days after injection of either amyloid or lipofuscin. At 1 month, however, ubiquitin, Alz-50 antigen, and silver-positive structures were observed only in response to amyloid. In 7 of 10 animals, there was considerable neuronal loss in the hippocampal layers. In each instance, these effects were in the immediate vicinity of beta-protein immunoreactive material. Marked neuronal loss was never observed at any time after lipofuscin injection. These results indicate a neuronal response to amyloid. When preparations of mature plaque amyloid isolated from the AD brain are injected into the rat brain, they exert neurotoxic effects and induce antigens found in the AD brain. PMID- 1924297 TI - 31P saturation transfer and phosphocreatine imaging in the monkey brain. AB - 31P magnetic resonance imaging with chemical-shift discrimination by selective excitation has been employed to determine the phosphocreatine (PCr) distribution in the brains of three juvenile macaque monkeys. PCr images were also obtained while saturating the resonance of the gamma-phosphate of ATP, which allowed the investigation of the chemical exchange between PCr and the gamma-phosphate of ATP catalyzed by creatine kinase. Superposition of the PCr images over the proton image of the same monkey brain revealed topological variations in the distribution of PCr and creatine kinase activity. PCr images were also obtained with and without visual stimulation. In two out of four experiments, an apparently localized decrease in PCr concentration was noted in visual cortex upon visual stimulation. This result is interpreted in terms of a possible role for the local ADP concentration in stimulating the accompanying metabolic response. PMID- 1924298 TI - Evolution of aminoacyl-tRNA synthetase quaternary structure and activity: Saccharomyces cerevisiae mitochondrial phenylalanyl-tRNA synthetase. AB - Phenylalanyl-tRNA synthetases [L-phenylalanine:tRNAPhe ligase (AMP-forming), EC 6.1.1.20] from Escherichia coli, yeast cytoplasm, and mammalian cytoplasm have an unusual conserved alpha 2 beta 2 quaternary structure that is shared by only one other aminoacyl-tRNA synthetase. Both subunits are required for activity. We show here that a single mitochondrial polypeptide from Saccharomyces cerevisiae is an active phenylalanyl-tRNA synthetase. This protein (the MSF1 gene product) is active as a monomer. It has all three characteristic sequence motifs of the class II aminoacyl-tRNA synthetases, and its activity may result from the recruitment of additional sequences into an alpha-subunit-like structure. PMID- 1924299 TI - Constant denaturant gel electrophoresis as a rapid screening technique for p53 mutations. AB - At present, mutation of the p53 gene appears to be the most common genetic alteration found in human cancers. These mutations can occur within many different regions of the gene. We have developed a modification of denaturing gradient gel electrophoresis termed "constant denaturant gel electrophoresis" (CDGE), which provides a rapid and sensitive method to screen the four conserved regions within the p53 gene where the majority of p53 mutations have been reported. The sensitivity of CDGE was first tested with known p53 mutations in all four conserved regions. The CDGE technique was then used to screen 32 breast carcinomas that had been analyzed by immunohistochemical methods for altered p53 protein levels and whose DNA had already been shown to have loss of heterozygosity for a chromosome 17p marker. By immunostaining techniques, only 6 of the 32 tumors had elevated p53 expression. However, CDGE detected p53 mutations in 11 of the 32 tumors. DNA sequence analysis was performed to determine the nucleotide positions of these mutations in all 11 samples. Loss of heterozygosity for the pYNZ22 or p144D6 markers did not associate with either the loss of heterozygosity at the p53 locus or the mutations detected by CDGE. We conclude that CDGE is a rapid and effective technique to screen for p53 mutations. PMID- 1924300 TI - Structural determinants of stereospecificity in yeast alcohol dehydrogenase. AB - Replacing Leu-182 by Ala in yeast alcohol dehydrogenase (YADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) yields a mutant that retains 34% of its kcat value and makes one stereochemical "mistake" every 850,000 turnovers (instead of approximately 1 error every 7,000,000,000 turnovers in native YADH) in its selection of the 4-Re hydrogen of NADH. Half of the decrease in stereochemical fidelity comes from an increase in the rate of transfer of the 4-Si hydrogen of NADH. The mutant also accepts 5-methylnicotinamide adenine dinucleotide, a cofactor analog not accepted by native YADH. The stereospecificity of the mutant is lower still with analogs of NADH where the carboxamide group of the nicotinamide ring is replaced by groups with weaker hydrogen bonding potential. For example, with thio-NADH, the mutant enzyme makes 1 stereochemical "mistake" every 450 turnovers. Finally, the double mutant T157S/L182A, in which Thr-157 is replaced by Ser and Leu-182 is replaced by Ala, also shows decreased stereochemical fidelity. These results suggest that Si transfer in the mutant enzymes arises from NADH bound in a syn conformation in the active site and that this binding is not obstructed in native YADH by side chains essential for catalysis. PMID- 1924301 TI - Endocytosis by the asialoglycoprotein receptor is independent of cytoplasmic serine residues. AB - The human asialoglycoprotein (ASGP) receptor, like most other plasma membrane receptors, has previously been shown to be phosphorylated at serine residues within the cytoplasmic domain. Phorbol esters, which activate protein kinase C, cause hyperphosphorylation and down-regulation of the ASGP receptor in HepG2 cells. To test the importance of serine residues for receptor traffic and function, we have mutated all the cytoplasmic serines of the two receptor subunits H1 (at positions 16 and 37) and H2 (at positions 12, 13, and 55) to alanines or glycines. Stable transfected fibroblast cell lines expressing either mutant H1 alone or both mutant subunits together were created and compared to cell lines expressing the respective wild-type proteins. Mutant and wild-type subunits were found to have very similar distributions between the cell surface and intracellular compartments. Constitutive internalization of H1 alone and ligand uptake and degradation by cells expressing both receptor subunits were not affected by the mutations. Cytoplasmic serines and serine phosphorylation are thus not essential for receptor function and intracellular traffic. Analysis of individual serine mutations identified serine-12 of subunit H2 as the major site of phosphorylation in the ASGP receptor. PMID- 1924303 TI - Catalytic properties of an Escherichia coli formate dehydrogenase mutant in which sulfur replaces selenium. AB - Formate dehydrogenase H of Escherichia coli contains selenocysteine as an integral amino acid. We have purified a mutant form of the enzyme in which cysteine replaces selenocysteine. To elucidate the essential catalytic role of selenocysteine, kinetic and physical properties of the mutant enzyme were compared with those of wild type. The mutant and wild-type enzymes displayed similar pH dependencies with respect to activity and stability, although the mutant enzyme profiles were slightly shifted to more alkaline pH. Both enzymes were inactivated by reaction with iodoacetamide; however, addition of the substrate, formate, was necessary to render the enzymes susceptible to alkylation. Alkylation-induced inactivation was highly dependent on pH, with each enzyme displaying an alkylation vs. pH profile suggestive of an essential selenol or thiol. Both forms of the enzyme use a ping-pong bi-bi kinetic mechanism. The mutant enzyme binds formate with greater affinity than does the wild-type enzyme, as shown by reduced values of Km and Kd. However, the mutant enzyme has a turnover number which is more than two orders of magnitude lower than that of the native selenium-containing enzyme. The lower turnover number results from a diminished reaction rate for the initial step of the overall reaction, as found in kinetic analyses that employed the alternative substrate deuterioformate. These results indicate that the selenium of formate dehydrogenase H is directly involved in formate oxidation. The observed differences in kinetic properties may help explain the evolutionary conservation of selenocysteine at the enzyme's active site. PMID- 1924302 TI - Two sites in the tissue factor extracellular domain mediate the recognition of the ligand factor VIIa. AB - Tissue factor (TF) binds the serine protease coagulation factor VIIa and initiates the coagulation protease cascade by forming a catalytic cofactor-enzyme complex. Using a photoactivatable crosslinking reagent coupled to factor VIIa, we have identified interactive sites in the amino-terminal (residues 44-84) and the carboxyl-terminal (residues 129-169) aspect of the extracellular domain of TF. Epitopes of inhibitory antibodies have previously indicated participation of these regions in TF function. The presence of the gamma-carboxyglutamic acid domain in factor VIIa appears to facilitate the interaction with the negatively charged, amino-proximate site, whereas crosslinking of TF with VIIa or des-(1-38) VIIa at the positively charged carboxyl-proximate site was similar. Lack of alpha helical secondary structure in the TF extracellular domain is consistent with the proposed structural similarity of TF with the cytokine receptor family. The interactive sites identified for TF are located in sequence spans that demonstrate a low degree of sequence conservation among the members of this receptor family. Regions with highly conserved residues, such as sequences encoded by exon 2 and 5 in TF, were not implicated in ligand recognition, suggesting that conserved residues in the receptor family may maintain the common beta-strand architecture, and variable regions provide a pair of nonidentical motifs for oriented ligand recognition. PMID- 1924304 TI - Architectural rules of the zinc-finger motif: comparative two-dimensional NMR studies of native and "aromatic-swap" domains define a "weakly polar switch". AB - The Zn-finger motif, encoding a globular minidomain with characteristic structure, provides a striking example of a sequence template for protein folding. Insight into architectural rules relating the amino acid sequence of a protein to its structure and stability may be obtained by comparative study of analogues. As our first step toward defining such rules for the Zn finger, we have recently described the design of an "aromatic-swap" analogue based on the ZFY two-finger repeat: a conserved alternation in sequence pattern observed among odd- and even-numbered domains in a family of sex-related vertebrate transcription factors. Consensus and "swapped" aromatic residues, introduced as revertants of less stable "aromaticless" analogues, were observed to provide equivalent contributions to the thermodynamic stability of the Zn finger. Here we describe and compare the solution structures of a wild-type domain and an aromatic-swap analogue, as determined by two-dimensional NMR and distance geometry/restrained molecular dynamics calculations. The wild-type and aromatic swap analogue each contain an N-terminal beta-sheet and a C-terminal alpha-helix (beta beta alpha motif), as observed in other systems, and exhibit a highly ordered hydrophobic core in which the native or swapped aromatic ring is closely packed. Remarkably, however, the two structures are stabilized by alternative aromatic-aromatic interactions, which in turn alter the respective DNA-binding surfaces. Our results suggest that native and swapped Zn-finger sequences encode a "weakly polar switch" between thermodynamically equivalent but functionally distinct architectures for DNA recognition. PMID- 1924305 TI - A human nuclear uracil DNA glycosylase is the 37-kDa subunit of glyceraldehyde-3 phosphate dehydrogenase. AB - We have isolated and characterized a plasmid (pChug 20.1) that contains the cDNA of a nuclear uracil DNA glycosylase (UDG) gene isolated from normal human placenta. This cDNA directed the synthesis of a fusion protein (Mr 66,000) that exhibited UDG activity. The enzymatic activity was specific for a uracil containing polynucleotide substrate and was inhibited by a glycosylase antibody or a beta-galactosidase antibody. Sequence analysis demonstrated an open reading frame that encoded a protein of 335 amino acids of calculated Mr 36,050 and pI 8.7, corresponding to the Mr 37,000 and pI 8.1 of purified human placental UDG. No homology was seen between this cDNA and the UDG of herpes simplex virus, Escherichia coli, and yeast; nor was there homology with the putative human mitochondrial UDG cDNA or with a second human nuclear UDG cDNA. Surprisingly, a search of the GenBank data base revealed that the cDNA of UDG was completely homologous with the 37-kDa subunit of human glyceraldehyde-3-phosphate dehydrogenase. Human erythrocyte glyceraldehyde-3-phosphate dehydrogenase was obtained commercially in its tetrameric form. A 37-kDa subunit was isolated from it and shown to possess UDG activity equivalent to that seen for the purified human placental UDG. The multiple functions of this 37-kDa protein as here and previously reported indicate that it possesses a series of activities, depending on its oligomeric state. Accordingly, mutation(s) in the gene of this multifunctional protein may conceivably result in the diverse cellular phenotypes of Bloom syndrome. PMID- 1924306 TI - Identification and partial characterization of six members of the kinesin superfamily in Drosophila. AB - Recent evidence has suggested that the principal polypeptide component of the microtubule motor protein kinesin may be a member of an extended superfamily of related motor proteins. To gain insight into how large the kinesin superfamily might be and to begin determining the potential functions in which various superfamily members might participate, we identified and partially characterized six additional members of the Drosophila kinesin superfamily. Genes encoding these proteins were identified by using the polymerase chain reaction with degenerate primers corresponding to highly conserved regions of the kinesin heavy chain motor domain. Partial sequencing of the six genes revealed that they encode proteins that are 40-60% identical to the motor domain of the kinesin heavy-chain sequence. The cytogenetic locations as well as the developmental and tissue specific expression patterns have been determined. The data suggest that each of these six kinesin-like proteins may have functions in a wide variety of cell types and tissues. PMID- 1924307 TI - Interleukin 1 is processed and released during apoptosis. AB - Interleukin (IL-) 1 alpha and 1 beta are synthesized as 31- to 34-kDa pro molecules. They are released from monocytes and macrophages as proteolytically processed 17-kDa mature molecules that bind with high affinity to specific receptors on target cells. IL-1 is not released via the classic secretory pathway. The pro molecules are synthesized as cytosolic proteins without signal peptides. Although the proteases that convert the pro molecules to the mature forms are cytosolic enzymes, processed IL-1 is not detected associated with the cell but is found only in culture supernatants. We demonstrate here that release of IL-1 is efficiently induced by cell injury. When the injury causes cellular necrosis, IL-1 alpha is released as a mixture of unprocessed and processed molecules but IL-1 beta is released exclusively as the biologically inactive pro form. In contrast, when cells undergo apoptosis, maturation of both IL-1 alpha and IL-1 beta is efficient. When apoptosis is rapid, as in macrophages that are targets for allospecific cytotoxic T lymphocytes, processing is observed to occur intracellularly. These findings suggest that cell injury is an important physiologic stimulus for release of IL-1. The nature of the injury profoundly affects the forms of IL-1 that are released. PMID- 1924308 TI - The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. AB - The virions of hepatitis delta virus (HDV) contain two species of HDV-specific protein, a large and a small form of hepatitis delta antigen (HDAg). We examined the role of individual HDAgs in virion assembly in cotransfection experiments. First, we constructed a replication-competent HDV mutant expressing only the small HDAg. When cotransfected with a plasmid expressing hepatitis B virus surface antigens to the HuH-7 cells, the mutant did not produce HDV virions, whereas the wild-type HDV clone did. Therefore, though the small HDAg is important for viral replication and is incorporated into the virus, the small form delta antigen by itself is insufficient for virion formation. When the system was co-transfected with an additional plasmid providing the large HDAg, the HDV virion was then recovered. There was also evidence suggesting that the large HDAg could be copackaged into the HBsAg particles, without the presence of the HDV genome and the small HDAg. The results indicate a crucial role of the large HDAg in HDV assembly. PMID- 1924309 TI - Isolation of a murine osteoclast colony-stimulating factor. AB - Cultures of a cell line derived from a murine mammary carcinoma that induces hypercalcemia were examined for soluble products that could induce osteoclasts to differentiate from murine bone marrow cells. The serum-free culture supernatant of this cell line stimulated growth of colonies from bone marrow cells that exhibited tartrate-resistant acid phosphatase (TRAPase) activity. These TRAPase positive cells demonstrated essential features of osteoclasts when cultured with mineralized bone or dentin. The culture period required for colony development and the frequency of colony-forming cells indicated that relatively primitive marrow progenitors were stimulated by a tumor-derived factor(s) to form immature osteoclasts. Other colony-stimulating factors (CSFs), including granulocyte CSF, macrophage CSF, granulocyte-macrophage CSF and interleukin 3, were ruled out as the source of the activity produced by the tumor cells. The biological activity was successfully purified by gel filtration chromatography and reverse-phase HPLC. By SDS/PAGE, the activity was traced to a protein of approximately 17 kDa. Functional and biochemical studies of the purified factor suggest that it is distinct from any known CSF of myeloid cells. This protein appears to be a CSF for the osteoclast lineage, osteoclast CSF (O-CSF). PMID- 1924311 TI - Baculovirus-mediated expression of human apolipoprotein E in Manduca sexta larvae generates particles that bind to the low density lipoprotein receptor. AB - Human apolipoprotein E (apoE) is a ligand for the low density lipoprotein (LDL) receptor and mediates the catabolism of several classes of lipoprotein particles. Binding of apoE to the LDL receptor requires association of apoE with lipid in a vesicle or a lipoprotein particle. Because of this requirement, purified apoE or apoE derived directly from bacterial expression systems does not bind to the LDL receptor. To overcome this problem and to facilitate analysis of apoE structure, recombinant baculoviruses containing the human apoE cDNA fused to the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus were constructed. The recombinant viruses were used to infect larvae of the tobacco hornworm Manduca sexta in vivo. High levels of lipoprotein particles containing human apoE were present in the hemolymph of infected larvae. In contrast to apoE produced by recombinant baculovirus-infected insect cells in vitro, these particles were excellent ligands for the LDL receptor. PMID- 1924310 TI - Sp1-dependent activation of a synthetic promoter by human immunodeficiency virus type 1 Tat protein. AB - The Tat protein coded by human immunodeficiency virus (HIV) is a strong activator of viral gene expression from the long terminal repeat (LTR). It appears that Tat mediated trans-activation of the HIV LTR is predominantly a transcriptional event. It has been reported that Tat acts at the level of both transcriptional initiation and elongation through interaction with a nascent RNA target sequence termed TAR (for trans-activation response element). However, the precise mechanism(s) by which Tat mediates TAR-dependent transcriptional activity is not known. To determine whether Tat functions similarly to other eukaryotic transcriptional activators through any of the conventional promoter elements, we tested Tat activity on synthetic promoters containing consensus sequences required for binding transcription factor Sp1 and a TATA box. Here, we report that a chimeric Tat protein targeted to the promoter region by the DNA-binding domain of yeast transcription factor GAL4 activates the synthetic promoter. Because this trans-activation depends on Sp1-binding sites, Tat can apparently mediate transcriptional activation through its interaction with Sp1. Mutational analysis of the gal4-tat chimeric gene reveals that the N-terminal 48-amino acid region of Tat constitutes the activation region for Sp1-dependent trans activation. This region of Tat exhibits substantially more activity than the N terminal 58 amino acids of Tat, which includes the arginine-rich basic region. Effects of specific mutations in the 48-amino acid Tat region of GAL4-Tat on trans-activation of the synthetic promoter mimic the effects of these specific mutations on Tat-mediated trans-activation of the HIV-1 LTR, suggesting that trans-activation of both the synthetic promoter and the intact LTR occurs by a common mechanism. PMID- 1924312 TI - Vitamin D3 binding protein (group-specific component) is a precursor for the macrophage-activating signal factor from lysophosphatidylcholine-treated lymphocytes. AB - A brief (30 min) treatment of mouse peritoneal cells (mixture of nonadherent lymphocytes and adherent macrophages) with 1-20 micrograms of lysophosphatidylcholine (lyso-PC) per ml in serum-supplemented RPMI medium 1640, followed by a 3-hr cultivation of the adherent cells alone, results in a greatly enhanced Fc receptor-mediated phagocytic activity of macrophages. This rapid process of macrophage activation was found to require a serum factor, the vitamin D3 binding protein (the human protein is known as group-specific component; Gc). Efficient activation of macrophages was achieved by using medium containing purified human Gc protein. Analysis of intercellular signal transmission among nonadherent (B and T) cells revealed that lyso-PC-treated B cells modify Gc protein to yield a proactivating factor, which can be converted by T cells to the macrophage-activating factor. This rapid generation process of the macrophage activating factor was also demonstrated by stepwise incubation of Gc protein with lyso-PC-treated B-cell ghosts and untreated T-cell ghosts, suggesting that Gc protein is modified by preexisting membranous enzymes to yield the macrophage activating factor. Incubation of Gc protein with a mixture of beta-galactosidase and sialidase efficiently generated the macrophage-activating factor. Stepwise incubation of Gc protein with B- or T-cell ghosts and sialidase or beta galactosidase revealed that Gc protein is modified by beta-galactosidase of B cells and sialidase of T cells to yield the macrophage-activating factor. Administration to mice of a minute amount (4-10 pg per mouse) of in vitro, enzymatically generated macrophage-activating factor resulted in a greatly enhanced (3- to 7-fold) ingestion activity of macrophages. PMID- 1924313 TI - Inhibition of acute inflammation in the periphery by central action of salicylates. AB - Understanding of the antiinflammatory actions of nonsteroidal drugs is incomplete, but these actions are believed to occur in the periphery, without any contribution from the central nervous system. Recent research on the antipyretic antiinflammatory neuropeptide alpha-melanocyte-stimulating hormone indicates that it can act centrally to inhibit peripheral inflammation; this raises the possibility that other agents, such as nonsteroidal antiinflammatory drugs, may have similar activity. In the present research both lysine acetylsalicylate and sodium salicylate inhibited edema, induced in the mouse ear by topical application of picryl chloride, when injected into the lateral cerebral ventricle. This inhibitory activity on a measure of acute inflammation was not due to escape of the drugs into the periphery, because systemic injection of doses that were effective centrally did not affect inflammation. In contrast, central administration of a dose of indomethacin that was antiinflammatory when given intraperitoneally did not inhibit peripheral inflammation. Thus indomethacin apparently lacks the central antiinflammatory action of the salicylates. This observation, plus our inability to demonstrate either an antiinflammatory effect of intracerebroventricular dexamethasone, a prostaglandin inhibitor, or a pro-inflammatory influence of prostaglandin E2, suggests that prostaglandins are not important to central modulation of inflammation. The results indicate that, in addition to having central influences on fever and pain, salicylates can act within the brain to inhibit acute inflammation in the periphery. PMID- 1924314 TI - A bacterial analog of the mdr gene of mammalian tumor cells is present in Streptomyces peucetius, the producer of daunorubicin and doxorubicin. AB - Sequence analysis of the drrAB locus from Streptomyces peucetius (American Type Culture Collection 29050) reveals the presence of two genes, drrA and drrB, both of which are required for daunorubicin and doxorubicin (Adriamycin) resistance in the heterologous host Streptomyces lividans. The DrrA protein is similar to a large family of ATP-binding transport proteins, including the proteins encoded by the mdr genes from mammalian tumor cells, which confer resistance to daunorubicin, doxorubicin, and some other structurally unrelated chemotherapeutic agents. The DrrB protein shows no significant similarity to other known proteins but is probably very hydrophobic, suggesting that it is located in the bacterial membrane. These two proteins may act jointly to confer daunorubicin and doxorubicin resistance by an analog of the antiport mechanism established for mammalian tumor cells that contain amplified or overexpressed mdr genes. Transcriptional analysis of the drrAB region supports the presence of one transcript containing drrA and drrB and indicates that these genes are expressed only during antibiotic production. PMID- 1924315 TI - ACE1, a copper-dependent transcription factor, activates expression of the yeast copper, zinc superoxide dismutase gene. AB - Copper, zinc superoxide dismutase (SOD1 gene product) (superoxide:superoxide oxidoreductase, EC 1.15.1.1) is a copper-containing enzyme that functions to prevent oxygen toxicity. In the yeast Saccharomyces cerevisiae, copper levels exert some control over the level of SOD1 expression. We show that the ACE1 transcriptional activator protein, which is responsible for the induction of yeast metallothionein (CUP1) in response to copper, also controls the SOD1 response to copper. A single binding site for ACE1 is present in the SOD1 promoter region, as demonstrated by DNase I protection and methylation interference experiments, and is highly homologous to a high-affinity ACE1 binding site in the CUP1 promoter. The functional importance of this DNA-protein interaction is demonstrated by the facts that (i) copper induction of SOD1 mRNA does not occur in a strain lacking ACE1 and (ii) it does not occur in a strain containing a genetically engineered SOD1 promoter that lacks a functional ACE1 binding site. PMID- 1924316 TI - Polymorphic sites in the African population detected by sequence analysis of the glucose-6-phosphate dehydrogenase gene outline the evolution of the variants A and A-. AB - The human X chromosome-linked gene encoding glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) is known to be highly polymorphic from the biochemical characterization of enzyme variants. The variant A (with enzyme activity in the normal range) and the variant A- (associated with enzyme deficiency) each have a frequency of about 0.2 in several African populations. Two restriction fragment length polymorphisms have also been found in people of African descent, but not in other populations, whereas a silent mutation has been shown to be polymorphic in Mediterranean, Middle Eastern, African, and Indian populations. We report now on two additional polymorphisms that we have detected by sequence analysis, one in intron 7 and one in intron 8. The analysis of 54 African male subjects for the seven polymorphic sites, clustered within 3 kilobases of the G6PD gene, has revealed only 7 of the 128 possible haplotypes, indicating marked linkage disequilibrium. These data have enabled us to suggest an evolutionary pathway for the different mutations, with only a single ambiguity. The mutation underlying the A variant is the most ancient and the mutation underlying the A- variant is the most recent. Since it seems reasonable that the A- allele is subject to positive selection by malaria, whereas the other alleles are neutral, G6PD may lend itself to the analysis of the role of random genetic drift and selection in determining allele frequencies within a single genetic locus in human populations. PMID- 1924317 TI - Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death. AB - Clone pTB16 has been isolated by differential screening of a human glioma cDNA library. Northern blot analysis has shown that pTB16 expression is several times (greater than 11-fold) higher in gliomas than in a primitive neuroectodermal tumor. This observation was supported by in situ hybridization and extended to nine other gliomas. Expression was virtually absent in adenocarcinoma cells metastasized to brain. Malignant gliomas showed stronger hybridization than benign gliomas, while blood capillaries did not show hybridization. pTB16 mRNA was also shown to be expressed in established glioma cell lines and at high levels in epileptic foci, indicating that expression of the gene may be limited to certain cell types and that its upregulation is not merely a consequence of cellular proliferation. Nucleotide sequence analysis identified pTB16 as the human counterpart for rat testicular sulfated glycoprotein 2 (SGP-2), whose function in the reproductive system remains unknown. Although SGP-2 transcripts, and hence pTB16, were recently shown to be increased in neurodegenerative diseases such as scrapie in hamsters and Alzheimer disease in humans, our observations with brain tumors and epilepsy are suggestive of a role for pTB16 in neuropathologies in general and support the hypothesis of its involvement in tissue remodeling and cell death. PMID- 1924318 TI - Ligand-binding and heterodimerization activities of a conserved region in the ligand-binding domain of the thyroid hormone receptor. AB - The ligand-binding domain of the thyroid hormone (3,5,3'-triiodothyronine) receptor (TR) contains poorly characterized subdomains involved with ligand binding, transactivation, and protein-protein interactions. The region between residues 288-331 of rat TR alpha-1 was analyzed by modeling and site-directed mutagenesis. Our results suggest that part of this sequence adopts an amphipathic alpha-helical conformation. The integrity of the putative helix is important for 3,5,3'-triiodothyronine binding but not necessarily for heterodimerization with nuclear factor(s). Mutants defective for both activities were found clustered in a region overlapping the C-terminal portion of the helix and further downstream. The sequence conservation of this particular region among the entire superfamily suggests a similar role in dimerization in other receptors. PMID- 1924319 TI - Regulated expression of the GAL4 activator gene in yeast provides a sensitive genetic switch for glucose repression. AB - Glucose (catabolite) repression is mediated by multiple mechanisms that combine to regulate transcription of the GAL genes over at least a thousandfold range. We have determined that this is due predominantly to modest glucose repression (4- to 7-fold) of expression of GAL4, the gene encoding the transcriptional activator of the GAL genes. GAL4 regulation is affected by mutations in several genes previously implicated in the glucose repression pathway; it is not dependent on GAL4 or GAL80 protein function. GAL4 promoter sequences that mediate glucose repression were found to lie downstream of positively acting elements that may be "TATA boxes." Two nearly identical sequences (10/12 base pairs) in this region that may be binding sites for the MIG1 protein were identified as functional glucose-control elements. A 4-base-pair insertion in one of these sites causes constitutive GAL4 synthesis and leads to substantial relief (50-fold) of glucose repression of GAL1 expression. Furthermore, promoter deletions that modestly reduce GAL4 expression, and therefore presumably the amount of GAL4 protein synthesized, cause much greater reductions in GAL1 expression. These results suggest that GAL4 works synergistically to activate GAL1 expression. Thus, glucose repression of GAL1 expression is due largely to a relatively small reduction of GAL4 protein levels caused by reduced GAL4 transcription. This illustrates how modest regulation of a weakly expressed regulatory gene can act as a sensitive genetic switch to produce greatly amplified responses to environmental changes. PMID- 1924320 TI - Complementation of snf1, a mutation affecting global regulation of carbon metabolism in yeast, by a plant protein kinase cDNA. AB - A cDNA, cRKIN1, encoding a putative homologue of the yeast (Saccharomyces cerevisiae) SNF1-encoded protein-serine/threonine kinase, has been isolated from a library prepared from rye endosperm mRNA. Northern blot analysis demonstrated the presence of cRKIN1-related transcripts in developing endosperms but not in shoots, and Southern blot analysis showed the presence of a small gene family. SNF1 plays a central role in carbon catabolite repression in yeast and expression of the RKIN1 sequence in yeast snf1 mutants restored SNF1 function. This suggests that the RKIN1 protein has a role in the control of carbon metabolism in endosperms of rye. PMID- 1924321 TI - A single base deletion in the Tfm androgen receptor gene creates a short-lived messenger RNA that directs internal translation initiation. AB - Testosterone-resistant male mice hemizygous for the X-chromosome-linked mutant gene Tfm express detectable but severely reduced levels of androgen receptor mRNA, amounting to about 10% of the level found in normal male littermates. No structural abnormality could be identified in the coding region of the messenger by a series of RNase-protection assays. However, cell-free translation of RNAs transcribed in vitro from enzymatically amplified overlapping segments of exon 1 revealed a truncated receptor protein and helped to localize the site of premature termination. Sequence analysis of the relevant DNA segment disclosed that deletion of a single nucleotide in the hexacytidine stretch at position 1107 1112 alters the reading frame of the messenger and introduces 41 missense amino acids before a premature termination codon at position 1235-1237. Separately initiated carboxyl-terminal polypeptides are synthesized in vitro, starting probably at the in-frame AUG codon 1507-1509, which lies in a favorable context for translation initiation, and at the non-AUG codon 1144-1146. Transcriptional impairments of the Tfm gene were ruled out by a quantitative analysis of enzymatically amplified nuclear RNA precursors. No other change could be identified by sequencing the complete coding region of Tfm cDNA. The finding of the unsuspected termination codon and the evidence of internally initiated carboxyl-terminal polypeptides reconcile previous conclusions and account for all known phenotypic properties of the mutation. PMID- 1924322 TI - Mammalian Sec23p homologue is restricted to the endoplasmic reticulum transitional cytoplasm. AB - The yeast Sec23 protein is required in vivo and in vitro for transport of proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. Ultrastructural localization of the Sec23p mammalian homologue (detected by antibody cross-reaction) in exocrine and endocrine pancreatic cells shows a specific distribution to the cytoplasmic zone between the transitional ER cisternae and Golgi apparatus where it appears associated with the tubular protuberances of the transitional ER cisternae, as well as with a population of vesicles, and surrounding cytoplasm. When ER-Golgi transport is interrupted with an energy poison, protuberances and transfer vesicles markedly decrease but Sec23p immunoreactive sites remain in the transitional cytoplasm not apparently tethered by membrane attachment. This unanticipated degree of organization suggests that cytosolic proteins, such as Sec23p, may be retained in specialized areas of the cytoplasm. A structure within the transitional zone may organize the flux of transport vesicles and Sec proteins so as to ensure efficient protein traffic in this limb of the secretory pathway. PMID- 1924323 TI - B3(Fv)-PE38KDEL, a single-chain immunotoxin that causes complete regression of a human carcinoma in mice. AB - The genes encoding the heavy- and light-chain Fv regions of the monoclonal murine antibody B3, which recognizes a carbohydrate antigen on the surface of many human carcinomas, were cloned by PCR techniques and used to generate single-chain immunotoxins containing Pseudomonas exotoxin (PE). The light and heavy chains were connected by a flexible linker to form a single-chain antigen-binding protein, B3(Fv), which was in turn fused to truncated forms of PE lacking the cell-binding domain. The single-chain Fv and two different B3(Fv) immunotoxins, B3(Fv)-PE40 and B3(Fv)-PE38KDEL, were expressed in Escherichia coli and the single-chain immunotoxins were purified to near homogeneity. Both recombinant immunotoxins were shown to be cytotoxic specifically to carcinoma cell lines that express the B3 antigen on their surface; B3(Fv)-PE38KDEL was significantly more active. Furthermore, intravenous administration of B3(Fv)-PE38KDEL caused complete regression of human epidermoid carcinomas growing subcutaneously in immunodeficient mice. PMID- 1924324 TI - Enzymatic modification of proteins with a geranylgeranyl isoprenoid. AB - The prenylation of several proteins involved in oncogenesis and signal transduction plays an essential role in regulating their biological activities. Two distinct isoprenoids are known to be involved in this modification, the 15 carbon farnesyl and 20-carbon geranylgeranyl groups. Thus far, identified farnesylated proteins contain methionine or serine at the COOH terminus, while those modified by geranylgeranyl end in leucine. This report describes the characterization of an enzyme activity that transfers the geranylgeranyl group to candidate proteins. The enzyme, termed a "protein geranylgeranyltransferase," exhibits a marked preference for substrate proteins that contain leucine at the COOH terminus. In fact, the enzyme will efficiently modify a normally farnesylated protein, Ha-ras, if its COOH-terminal amino acid is switched from serine to leucine. Additional studies characterize this enzyme and suggest that it is responsible for the geranylgeranyl modification of a number of GTP-binding proteins (or their subunits) that contain a consensus prenylation sequence ending in leucine. PMID- 1924325 TI - A second thrombospondin gene in the mouse is similar in organization to thrombospondin 1 but does not respond to serum. AB - A second, expressed thrombospondin (TSP) gene, Thbs2, has been identified in the mouse. The exon/intron organization of Thbs2 is highly conserved in comparison with Thbs1 in that exon size and the pattern of interruption of the reading frame by introns are preserved, but there is a marked divergence in coding sequence, primarily in the first 7 exons. On the other hand, the DNA and translated amino acid sequences of exons coding for the type I, II, and III repeats in the two TSPs are far better conserved. Thbs2 is located on chromosome 17, band A3, whereas Thbs1 was found on chromosome 2, band F. In marked contrast to Thbs1, the Thbs2 gene is not induced by serum in NIH 3T3 cells; promoter sequences in the two genes are also very different. It is therefore likely that the two TSPs perform related but distinct functions. PMID- 1924326 TI - A soluble, single-chain T-cell receptor fragment endowed with antigen-combining properties. AB - A strategy for the production of small, soluble, single-chain T-cell receptor (scTCR) fragments that carry an intact TCR antigen-combining site is presented. The rationale is based on structural similarity between TCR and antibody molecules and use of computer modeling methods to derive a model structure of a human scTCR variable (V)-domain dimer. A gene encoding the RFL3.8 TCR protein, specific for the hapten fluorescein in the context of major histocompatibility complex class II and composed of one V alpha and one V beta domain joined via a flexible peptide linker, was assembled in an Escherichia coli plasmid. Subsequently, the protein was produced in a bacterial expression system, purified, refolded, and found to be poorly soluble at neutral pH in aqueous buffers. An inspection of the computer-generated V alpha-V beta domain model showed several surface exposed hydrophobic residues. When these were replaced by water-soluble side chains via site-directed mutagenesis of the corresponding gene, a soluble protein resulted and was shown to have antigen-binding properties equivalent to those of the intact TCR of the RFL3.8 T-cell clone. These results demonstrate the feasibility of obtaining TCR fragments endowed with antigen combining properties by protein engineering in E. coli. PMID- 1924328 TI - A different perception of the linear, nonthreshold hypothesis for low-dose irradiation. AB - Two equally useful dosimetric quantities, both of which are called dose, are used in toxicology. With radiation measurement, only one--the energy per unit mass D- is called dose. The other--the total energy in the irradiated system--is here distinguished from D by assigning it the name collective energy, epsilon. The collective energy is a more complete statement of dose because it is the product of the energy concentration D and the mass irradiated m. Especially in radioepidemiology, in which epsilon is the total energy imparted to all persons irradiated, the quantity m must be specified because it is situation specific and thus highly variable. At present, radioepidemiological dose-response curves are given only in terms of the toxicological model--i.e., the fraction (probability) of radiation-attributable cancers occurring as a function of D. Because this relation does not involve the number of persons at each value of D, it fosters the illusion that any dose, no matter how small, can result in cancer. However, we show that if the dose-response relationship is expressed in terms of the absolute number of attributable cancers as a function of epsilon, cancer occurs, on average, only if the collective energy exceeds a relatively large minimum value, the magnitude of which will be estimated. Therefore, we conclude that the nonthreshold aspect of the linear hypothesis is misleading and quite probably invalid. For example, in or around a facility in which exposure of humans to relatively low values of D occurs, attributable cancers are most unlikely to appear unless the epsilon to the irradiated population exceeds this minimum value. PMID- 1924327 TI - Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. AB - The biological functions of the BCL2 gene were investigated in transgenic mice harboring human BCL2 cDNA under the control of an immunoglobulin heavy chain enhancer (E mu). Mice of a representative transgenic strain, E mu-bcl-2-22, had a great excess of B lymphocytes, immunoglobulin-secreting cells, and serum immunoglobulins, attributable to increased longevity of B-lineage cells. Pre-B and plasma cells as well as B cells exhibited prolonged survival in culture. Immunized animals produced an amplified and protracted antibody response. Within the first year of life, most mice spontaneously produced antibodies to nuclear antigens, and 60% developed kidney disease, diagnosed as immune complex glomerulonephritis. Thus E mu-bcl-2-22 mice constitute a transgenic model for a systemic autoimmune disease resembling the human disorder systemic lupus erythematosus. PMID- 1924330 TI - Metabolic rate of membrane-permeant diacylglycerol and its relation to human resting T-lymphocyte activation. AB - DL-1,2-Dioctanoylglycerol (1,2-DiC8) added to human peripheral resting T lymphocytes was rapidly metabolized to produce octanoic acid and further to small molecules, probably by the action of diacylglycerol lipase and/or nonspecific esterase. Only a small portion was converted to the corresponding phosphatidic acid or was isomerized to 1,3-DiC8 before being metabolized. The uptake of 1,2 DiC8 by the cell was apparently fast, and the rate of disappearance of 1,2-DiC8 was dependent on the cell densities; at a higher density of T lymphocytes 1,2 DiC8 was removed quickly, whereas at a lower cell density 1,2-DiC8 remained for a longer period of time. With a fixed amount of 1,2-DiC8 added, the extent of interleukin 2 receptor alpha-subunit (IL-2R alpha) expression was inversely related to the cell density and proportional to the duration of exposure of the cells to 1,2-DiC8. Repeated doses of 1,2-DiC8 potentiated IL-2R alpha expression. In contrast, a single dose of phorbol 12-myristate 13-acetate caused T-lymphocyte activation to similar extents irrespective of the cell density, probably because the phorbol ester was not metabolized and remained in membranes. The available evidence supports a proposal made in a previous paper and indicates that the sustained activation of protein kinase C for at least the first 3-4 hr is essential for the activation of resting T lymphocytes. PMID- 1924329 TI - Protein-DNA interactions in vivo of an erythroid-specific, human beta-globin locus enhancer. AB - The 5' DNase I-hypersensitive site 2 (5' HS-2) is an erythroid-specific enhancer located 11 kilobases (kb) upstream of the human beta-globin gene cluster. Presence in cis of 5' HS-2 confers a high level of erythroid cell-specific and developmentally regulated promoter activities of human globin genes in transfected cell cultures and in transgenic mice. Combining the use of the methylation protection assay and polymerase chain reaction, we have studied nuclear factor-DNA interactions of the 5' HS-2 enhancer in vitro and in vivo. The data from analyses of three different sequence motifs within 5' HS-2 represent three different modes of protein-DNA interaction with respect to cell-type specificities and in vivo vs. in vitro differences. First, a GATA-1 motif was found to bind nuclear factor(s), presumably the GATA-1 factor, present in K-562 cell extracts and in living K-562 cells. No such binding was seen in nonerythroid HeLa cells or extract. A second motif, NF-E2/AP1 (nuclear factor-erythroid 2/activator protein 1), consists of tandemly arranged dimers of AP1 binding consensus. The presence of either HeLa extract or K-562 extract protects the NF E2/AP1 motif from methylation, but the footprints are different. This is most likely due to different protein-DNA contacts of the AP1-DNA complex formed in HeLa extract and the NF-E2-DNA complex in K-562 extract. In vivo methylation protection patterns of this motif parallel those observed in vitro, suggesting that it is also bound by NF-E2 in K-562 cells and by AP1 in HeLa cells. Finally, a GT-I motif binds apparently to one or more similar factors in both types of nuclear extracts, but the in vivo methylation protection patterns are not identical between living HeLa and K-562 cells. These data provide direct evidence that specific nuclear factor-DNA complexes form in vivo at functionally important sequence motifs of the 5' HS-2 enhancer in erythroid cells. The detection of conformationally different nuclear factor-DNA complexes at the same sequence motifs in HeLa and Raji cell lines also raises interesting questions regarding the origin and function of these complexes in nonerythroid cells. PMID- 1924331 TI - Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice. AB - Synthesis of erythropoietin, the primary humoral regulator of erythropoiesis, in liver and kidney is inducible by anemia or hypoxia. Analysis of human erythropoietin gene expression in transgenic mice revealed that sequences located 6-14 kilobases 5' to the gene direct expression to the kidney, whereas sequences within the immediate 3'-flanking region control hepatocyte-specific expression. Human erythropoietin transcription initiation sites were differentially utilized in liver and kidney. Inducible transgene expression was precisely targeted to peritubular interstitial cells in the renal cortex that synthesize endogenous mouse erythropoietin. These studies demonstrate that multiple erythropoietin gene regulatory elements control cell-type-specific expression and inducibility by a fundamental physiologic stimulus, hypoxia. PMID- 1924332 TI - Self peptide requirement for class II major histocompatibility complex allorecognition. AB - Using a dinitrophenylated and biotinylated peptide antigen, we have developed an affinity chromatography procedure to purify complexes of a given peptide species and a given class II major histocompatibility complex antigen away from class II molecules occupied by other peptides. We show that hen egg lysozyme peptide-I-Ed complexes purified according to this procedure have a greatly enhanced capacity to activate hen egg lysozyme-specific T cells but have lost the capacity to activate three different alloreactive T-cell hybridomas. These data demonstrate that the class II molecule in and of itself is not sufficient to activate alloreactive T cells. Rather, the data suggest that recognition of specific complexes formed between allo-class II and particular autologous peptides may be required. Alternatively, alloreactive T cells may be recognizing "empty" major histocompatibility complex molecules. PMID- 1924333 TI - Induction of plasmacytomas secreting antigen-specific monoclonal antibodies with a retrovirus expressing v-abl and c-myc. AB - ABL-MYC, a recombinant murine retrovirus that expresses v-abl and c-myc, rapidly induces transplantable mono- or oligoclonal plasmacytomas in BALB/c mice. To determine if the targets for transformation of this retrovirus are antigen committed B lymphocytes and to explore this system as an alternative technique for producing antigen-specific monoclonal antibodies, plasmacytomas were induced in mice that had been immunized with two different types of immunogens, hen egg white lysozyme and sheep red blood cells. The majority of these plasmacytomas secreted immunogen-specific antibodies. Plasmacytomas induced in unimmunized mice did not react with hen egg white lysozyme or sheep red blood cells. The specific antibodies were comparable in concentration, specificity, and affinity to monoclonal antibodies obtained with conventional hybridoma technology, but, in addition to IgGs and IgMs, they included specific IgA antibodies, which are rare among splenic-derived hybridomas. Our results demonstrate that a principal target for ABL-MYC is an antigen-committed B lymphocyte. In addition this procedure provides an alternative method for the production of monoclonal antibodies, without a requirement for hetero-caryon formation by cell fusion techniques. PMID- 1924334 TI - Expression of the rat growth hormone-releasing hormone gene in placenta is directed by an alternative promoter. AB - Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that plays a critical role in controlling the synthesis and secretion of growth hormone by the anterior pituitary. GHRH has also been detected in other nonneural extrahypothalamic tissues, including rat placenta, although its role in the hormonal control of pregnancy and/or fetal development has not yet been defined. Here we present the isolation and characterization of cDNA clones corresponding to rat placental GHRH. The placental GHRH mRNA codes for a pre-pro-GHRH identical to that found in the hypothalamus, suggesting that the mature placental GHRH is identical to its hypothalamic counterpart. Nevertheless, the placental and the hypothalamic GHRH mRNAs differ in the region corresponding to the untranslated exon 1 because of the use of an alternative promoter in the placenta located 10 kilobases upstream from the hypothalamic promoter. A combined mechanism involving the use of tissue-specific alternative promoters and the differential splicing of exon 1 generates the mature GHRH transcript in placenta and hypothalamus. Multiple transcription initiation sites have been found in the placental GHRH mRNA, which correlates to the lack of a consensus TATA box in the promoter region. PMID- 1924335 TI - Cloning, characterization, and autoimmune recognition of rat islet glutamic acid decarboxylase in insulin-dependent diabetes mellitus. AB - A 64-kDa islet protein is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). Autoantibodies against the 64-kDa protein were recently shown to immunoprecipitate glutamic acid decarboxylase (GAD; L-glutamate 1-carboxy-lyase, EC 4.1.1.15) from brain and from islets. We present evidence that the autoantisera also recognize a hydrophilic islet protein of approximately 67 kDa in addition to the amphiphilic 64-kDa form. We have isolated a full-length rat islet GAD cDNA encoding a hydrophilic 67-kDa protein, which appears to be identical to rat brain 67-kDa GAD. A partial sequence of human insulinoma 67-kDa GAD was identical to human brain 67-kDa GAD. Allelic variations were observed in rat as well as in human 67-kDa GAD sequences. The expressed rat islet 67-kDa GAD protein is functional and is immunoprecipitated by IDDM sera; it comigrates electrophoretically with the 67-kDa islet autoantigen. The hydrophilic 67-kDa form of GAD in islets is an additional autoantigen in IDDM and is recognized by a different subset of autoantibodies than the 64-kDa autoantigen. Thus, mammalian cell lines expressing functionally active, recombinant GAD may become important tools to study the nature and the role of GAD autoreactivity in IDDM. PMID- 1924336 TI - X-ray structure of trypanothione reductase from Crithidia fasciculata at 2.4-A resolution. AB - Trypanosomes and related protozoan parasites lack glutathione reductase and possess instead a closely related enzyme that serves as the reductant of a bis(glutathione)-spermidine conjugate, trypanothione. The human and parasite enzymes have mutually exclusive substrate specificities, providing a route for the design of therapeutic agents by specific inhibition of the parasite enzyme. We report here the three-dimensional structure of trypanothione reductase from Crithidia fasciculata and show that it closely resembles the structure of human glutathione reductase. In particular, the core structure surrounding the catalytic machinery is almost identical in the two enzymes. However, significant differences are found at the substrate binding sites. A cluster of basic residues in glutathione reductase is replaced by neutral, hydrophobic, or acidic residues in trypanothione reductase, consistent with the nature of the spermidine linkage and the change in overall charge of the substrate from -2 to +1, respectively. The binding site is more open in trypanothione reductase due to rotations of about 4 degrees in the domains that form the site, with relative shifts of as much as 2-3 A in residue positions. These results provide a detailed view of the residues that can interact with potential inhibitors and complement previous modeling and mutagenesis studies on the two enzymes. PMID- 1924338 TI - Secreted acid phosphatase of Leishmania mexicana: a filamentous phosphoglycoprotein polymer. AB - In the promastigote, or insect stage, most species of the parasitic protozoan Leishmania secrete an acid phosphatase. The enzyme purified from the culture medium of Leishmania mexicana is shown to be a complex [13.3% (wt/wt) protein, 74.4% (wt/wt) carbohydrate, and 12.3% (wt/wt) phosphate] composed of a predominant phosphorylated glycoprotein with a relative molecular mass of 100 kDa and noncovalently associated high molecular mass (proteo)phosphoglycans. Electron microscopy discloses long filaments composed of a central chain of protein subunits surrounded by a diffuse glycocalix that can be decorated by monoclonal antibodies or concanavalin A. In contrast to the polymeric structure of the L. mexicana enzyme, the acid phosphatase secreted by Leishmania donovani is mono- or oligomeric but not filamentous. PMID- 1924339 TI - In vivo catalysis of a metabolically essential reaction by an antibody. AB - We have established a growth selection requirement for a catalytic antibody with modest chorismate mutase activity. Conversion of (-)-chorismate into prephenate is the key step in the biosynthesis of the aromatic amino acids tyrosine and phenylalanine. Strains of the yeast Saccharomyces cerevisiae containing an insertion mutation in the structural gene for the enzyme chorismate mutase (EC 5.4.99.5) require exogenous supplements of these two amino acids for efficient growth. Intracellular expression of the heterologous antibody catalyst in one such strain, identified by random mutagenesis and genetic selection, provides a substantial growth advantage under auxotrophic conditions; complementation was not observed with an unrelated esterolytic antibody. In addition to demonstrating that tailored immunoglobulin catalysts can carry out vital biochemical reactions in vivo, these experiments provide a powerful selection assay for identifying genetic changes within the antibody molecule itself that augment chemical efficiency. PMID- 1924337 TI - Engineering the substrate specificity of glutathione reductase toward that of trypanothione reduction. AB - Glutathione reductase (EC 1.6.4.2; CAS registry number 9001-48-3) and trypanothione reductase (CAS registry number 102210-35-5), which are related flavoprotein disulfide oxidoreductases, have marked specificities for glutathione and trypanothione, respectively. A combination of primary sequence alignments and molecular modeling, together with the high-resolution crystal structure of human glutathione reductase, identified certain residues as potentially being responsible for substrate discrimination. Site-directed mutagenesis of Escherichia coli glutathione reductase was used to test these predictions. The mutation of Asn-21 to Arg demonstrated that this single change was insufficient to generate the greater discrimination against trypanothione shown by human glutathione reductase compared with the E. coli enzyme. However, the mutation of Ala-18, Asn-21, and Arg-22 to the amino acid residues (Glu, Trp, and Asn, respectively) in corresponding positions in Trypanosoma congolense trypanothione reductase confirmed that this region of polypeptide chain is intimately involved in substrate recognition. It led to a mutant form of E. coli glutathione reductase that possessed essentially no activity with glutathione but that was able to catalyze trypanothione reduction with a kcat/Km value that was 10% of that measured for natural trypanothione reductases. These results should be of considerable importance in the design of trypanocidal drugs targeted at the differences between glutathione and trypanothione metabolism in trypanosomatids and their hosts. PMID- 1924340 TI - Germ-cell deficient (gcd), an insertional mutation manifested as infertility in transgenic mice. AB - A genetic analysis is necessary to gain a greater understanding of the complex developmental processes in mammals. Toward this end, an insertional transgenic mouse mutant has been isolated that results in abnormal germ-cell development. This recessive mutation manifests as infertility in both males and females and is specific for the reproductive organs, since all other tissues examined were histologically normal. A developmental analysis of the gonadal tissues demonstrated that the germ cells were specifically depleted as early as day 11.5 of embryonic development, while the various somatic cells were apparently unaffected. Therefore, the mutated locus must play a critical role in the migration/proliferation of primordial germ cells to the genital ridges of developing embryos. In addition, females homozygous for the mutation could potentially be a valuable animal model of a human syndrome, premature ovarian failure. This mutation has been named germ-cell deficient, gcd. PMID- 1924341 TI - The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA. AB - The polymeric immunoglobulin receptor (pIgR) on mucosal epithelial cells binds dimeric IgA (dIgA) on the basolateral surface and mediates transport of dIgA to the apical surface. Using Madin-Darby canine kidney epithelial cells stably transfected with pIgR cDNA, we found that soluble immune complexes (ICs) of 125I labeled rat monoclonal antidinitrophenyl (DNP) dIgA (125I-dIgA) and DNP/biotin bovine serum albumin were transported from the basolateral to the apical surface and then released. Monomeric IgA ICs were not transported, consistent with the specificity of pIgR for polymeric immunoglobulins. Essentially all the 125I-dIgA in apical culture supernatants was streptavidin precipitable, indicating that dIgA remained bound to antigen during transcytosis. While both dIgA and dIgA ICs bound pIgR with equal affinity (Kd approximately 8 nM), the number of high affinity binding sites per cell was 2- to 3-fold greater for dIgA than for dIgA ICs. The extent of endocytosis of dIgA and dIgA ICs was correlated with the number of high-affinity binding sites. SDS/PAGE analysis of intracellular dIgA and dIgA ICs demonstrated that in both cases IgA remained undegraded during transport. The results suggest that the pathways of epithelial transcytosis of free dIgA and dIgA ICs are the same. Given the high population density of mucosal IgA plasma cells and the enormous surface area of pIgR-expressing mucosal epithelium, it is likely that significant local transcytosis of IgA ICs occurs in vivo. Such a process would allow direct elimination of IgA ICs at the mucosal sites where they are likely to form, thus providing an important defense function for IgA. PMID- 1924342 TI - Nerve growth factor prevents the amblyopic effects of monocular deprivation. AB - Monocular deprivation early in life causes dramatic changes in the functional organization of mammalian visual cortex and severe reduction in visual acuity and contrast sensitivity of the deprived eye. We tested whether or not these changes could be from competition between the afferents from the two eyes for a target derived neurotrophic factor. Rats monocularly deprived during early postnatal development were treated with repetitive intraventricular injections or topical administration of nerve growth factor. The effects of monocular deprivation were then assessed electrophysiologically. In untreated animals visual acuity and contrast sensitivity of the deprived eye were strongly reduced, whereas in nerve growth factor-treated animals these parameters were normal. PMID- 1924343 TI - Studies on DNA-cleaving agents: computer modeling analysis of the mechanism of activation and cleavage of dynemicin-oligonucleotide complexes. AB - Dynemicin A is a recently identified antitumor antibiotic. Upon activation, dynemicin is reported to cause double-stranded cleavage of DNA, putatively through the intermediacy of a diradical. Computer modeling of this activation and cleavage process is described herein as part of an effort to establish a structural hypothesis for this mechanistic sequence and for the design of simple analogues. Intercalation complexes of duplex dodecamers [d(CGCGAATTCGCG)]2 and [d(GC)6]2 with both enantiomers of dynemicin and of all related mechanistic intermediates are evaluated. Examination of these structures shows that cycloaromatization of dynemicin to a diradical intermediate results in the rotation of the diradical-forming subunit with respect to the intercalation plane that is of an opposite sense for the two dynemicin enantiomers. In addition, the activation of the (2S) enantiomer of dynemicin occurs by a less restricted approach trajectory than the corresponding (2R) enantiomer. In all complexes, the 5'-3' strand is at least 1 A closer than the 3'-5' strand to the diyl intermediate. As a result, complexes are produced in which the diyl moiety is aligned along [(2S)] or across [(2R)] the minor groove, leading to different predictions for the selectivity of radical-initiated, oxidative lesion of DNA. Molecular dynamics simulations are found to support these predictions, including the 3-base-pair offset cleavage reported for dynemicin. PMID- 1924344 TI - Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa. AB - Thirteen mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa (ADRP) have been produced by transfection of cloned cDNA into tissue culture cells. Three mutants [class I: Phe-45----Leu, Gln-344----termination (deletion of C-terminal positions 344-348), and Pro-347----Leu] resemble wild type rhodopsin in yield, regenerability with 11-cis-retinal, and plasma membrane localization. Ten mutants [class II: Thr-17----Met, Pro-23----His, Thr-58----Arg, Val-87----Asp, Gly-89----Asp, Gly-106----Trp, Arg-135----Leu, Arg-135----Trp, Tyr 178----Cys, and Asp-190----Gly] accumulate to significantly lower levels, regenerate with 11-cis-retinal variably or not at all, and are transported inefficiently to the plasma membrane, remaining primarily in the endoplasmic reticulum. These data suggest that there are at least two distinct biochemical defects associated with different rhodopsin mutants in ADRP. PMID- 1924345 TI - Multiple forms of mouse 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase and differential expression in gonads, adrenal glands, liver, and kidneys of both sexes. AB - Observations of patients deficient in the steroidogenic enzyme 3 beta-hydroxy delta 5-steroid dehydrogenase/isomerase (3 beta HSD) have suggested the presence of distinct 3 beta HSD structural gene(s) that are expressed at peripheral sites, possibly the liver. We now report the isolation of cDNA clones representing three forms of 3 beta HSD from mouse Leydig cell and liver libraries. The three forms share significant identify but differ from each other by 5-10% within their coding regions. RNA that hybridizes to radiolabeled 3 beta HSD probes is present in the gonads, adrenal glands, liver, and kidneys of both sexes. Ribonuclease protection analysis using antisense probes derived from each of the three forms demonstrates that one form, 3 beta HSD I, is restricted to steroidogenic tissues. Two other forms, 3 beta HSD II and III, are expressed in liver and kidney but are not detected in steroidogenic tissues. A polyclonal antibody raised against the human placental form of 3 beta HSD recognizes a 42-kDa protein in gonadal and adrenal tissue and a 45-kDa protein in liver. The antibody recognizes a 42-kDa protein in kidney only weakly. 3 beta HSD enzyme activity is present in testicular, adrenal, hepatic, and renal tissue, with adrenal tissue possessing the highest specific activity. When expressed as total 3 beta HSD activity for whole organ mass, activity is greatest in the liver. The results demonstrate that the mouse liver is a significant site of 3 beta HSD activity and demonstrate the existence of multiple 3 beta HSD structural genes in the mouse. PMID- 1924347 TI - Distribution of glutamine and asparagine residues and their near neighbors in peptides and proteins. AB - In a statistical study of neighboring residues in 1465 peptides and proteins comprising 450,431 residues, it was found that the preferences for residues neighboring to glutamine and asparagine residues are consistent with the hypothesis that the rates of deamidation of these residues are of biological significance. Some dipeptide and tripeptide structures have special usefulness and some are especially undesirable. More such structures exist for amide residues than for other residues, and their specific types are those most relevant to the deamidation of amide residues under biological conditions. PMID- 1924346 TI - Isolation of a cellular protein that binds to the human immunodeficiency virus Tat protein and can potentiate transactivation of the viral promoter. AB - The human immunodeficiency virus type 1 Tat protein is a powerful transactivator of the viral long terminal repeat (LTR). We have identified a cellular protein that strongly binds to Tat and can complement Tat transactivation in rodent cells. The cellular protein of about 36 kDa was isolated from extracts of human cells by Tat peptide-affinity chromatography and can form a complex with Tat in vitro. Tat transactivation is inefficient in rodent cells microinjected or transfected with the reporter plasmid pHIV-LTRCAT plus the Tat-expressing plasmid pCV-1. Remarkably, coinjection of purified 36-kDa protein with pHIV-LTRCAT plus pCV-1 stimulated Tat transactivation 2.7- to 4.9-fold. Taken together, our findings suggest that the 36-kDa protein may be a transcription factor or modulator that is important for efficient Tat transactivation. PMID- 1924348 TI - Direct observation of vibrational coherence in bacterial reaction centers using femtosecond absorption spectroscopy. AB - It is shown that vibrational coherence modulates the femtosecond kinetics of stimulated emission and absorption of reaction centers of purple bacteria. In the DLL mutant of Rhodobacter capsulatus, which lacks the bacteriopheophytin electron acceptor, oscillations with periods of approximately 500 fs and possibly also of approximately 2 ps were observed, which are associated with formation of the excited state. The kinetics, which reflect primary processes in Rhodobacter sphaeroides R-26, were modulated by oscillations with a period of approximately 700 fs at 796 nm and approximately 2 ps at 930 nm. In the latter case, at 930 nm, where the stimulated emission of the excited state, P*, is probed, oscillations could only be resolved when a sufficiently narrow (10 nm) and concomitantly long pump pulse was used. This may indicate that the potential energy surface of the excited state is anharmonic or that low-frequency oscillations are masked when higher frequency modes are also coherently excited, or both. The possibility is discussed that the primary charge separation may be a coherent and adiabatic process coupled to low-frequency vibrational modes. PMID- 1924349 TI - Overexpression of c-jun, junB, or junD affects cell growth differently. AB - The coding sequences of murine c-jun, junB, or junD, which code for proteins with practically identical dimerization and DNA binding properties, were introduced into a nondefective retroviral vector, and the phenotype of primary avian fibroblasts chronically infected with each of these viruses was studied. Cells expressing c-jun grew in low-serum medium and developed into colonies in agar, two properties characteristic of in vitro transformation. Cells expressing junB grew in agar, with a reduced efficiency as compared to c-jun, but did not grow in low-serum medium. Finally, no effect of junD expression on cell growth was observed. These different phenotypes suggest that these three closely related transcription factors play distinct roles during normal cell growth. Analysis of c-jun deletion mutants and of c-jun/junB and c-jun/junD chimeric genes showed that the N-terminal portion (amino acids 2-168) of the c-Jun protein that is involved in transcriptional activation is required for efficient transformation. On the contrary, cells expressing a truncated mouse c-Jun lacking this N-terminal domain grew slower than normal embryo fibroblasts. The reduced growth rate may be related to the finding that expression of the intact or the truncated mouse c-jun repressed the endogenous avian c-Jun homologue, suggesting that functional c-Jun product is required for normal cell growth. PMID- 1924350 TI - Alzheimer beta/A4 amyloid precursor protein in human brain: aging-associated increases in holoprotein and in a proteolytic fragment. AB - Alzheimer beta/A4 amyloid precursor protein (APP) has been suggested to play a central role in the pathogenesis of Alzheimer disease. We have measured the content of different species of APP holoprotein and carboxyl-terminal fragments in human brains from young individuals, nondemented aged individuals, and aged individuals with Alzheimer disease. By using an antibody directed against the cytoplasmic domain of APP, five species were resolved. Three of these, of molecular masses 106, 113, and 133 kDa, represent presumptive immature and mature isoforms of APP holoprotein. Two smaller proteins, of molecular masses 15 and 19 kDa, represent presumptive proteolytic carboxyl-terminal fragments of APP. The 133-, 113-, 106-, and 15-kDa species were found in both grey and white matter, whereas the 19-kDa species was found only in grey matter. Total APP immunoreactivity (sum of all five species) and the levels of the 113-, 106-, and 15-kDa species were not significantly different in brain samples from young individuals, nondemented aged individuals, and aged individuals with Alzheimer disease. In contrast, the levels of the 133- and 19-kDa species increased 2- to 3 fold with age. A correlation was observed between the levels of the 133- and 19 kDa species, suggesting a possible precursor-product relationship. The size of the 19-kDa fragment indicated that it might have an intact beta/A4 domain and therefore be amyloidogenic. The age-dependent increase either in a mature APP isoform and/or in a putative amyloidogenic fragment could explain why Alzheimer disease is associated with advanced age. PMID- 1924351 TI - Copper resistance in Pseudomonas syringae mediated by periplasmic and outer membrane proteins. AB - Copper-resistant strains of Pseudomonas syringae pathovar tomato accumulate copper and develop blue colonies on copper-containing media. Three of the protein products of the copper-resistance operon (cop) were characterized to provide an understanding of the copper-resistance mechanism and its relationship to copper accumulation. The Cop proteins, CopA (72 kDa), CopB (39 kDa), and CopC (12 kDa), were produced only under copper induction. CopA and CopC were periplasmic proteins and CopB was an outer membrane protein. Leader peptide sequences of CopA, CopB, and CopC were confirmed by amino-terminal peptide sequencing. CopA, CopB, and CopC were purified from strain PT23.2, and their copper contents were determined. One molecule of CopA bound 10.9 +/- 1.2 atoms of copper and one molecule of CopC bound 0.6 +/- 0.1 atom of copper. The Cop proteins apparently mediate sequestration of copper outside of the cytoplasm as a copper-resistance mechanism. PMID- 1924352 TI - A blue-light-activated GTP-binding protein in the plasma membranes of etiolated peas. AB - Heterotrimeric GTP-binding regulatory proteins (G proteins) have been identified as part of signal transduction systems in a wide variety of organisms. In this paper, we establish the presence of a G protein associated with the plasma membranes of the apical bud of etiolated peas. The GTPase activity is induced by low fluences of blue light administered to plasma membrane-enriched fractions. The activity is not responsive to red-light irradiation and is specific for GTP. The threshold for the excitation of the GTPase activity in vitro is less than 10( 1) mumol.m-2 of blue light, consistent with participation in the blue low-fluence system identified in the same tissue. A 40-kDa polypeptide is recognized by polyclonal antisera directed against the alpha subunit of the G protein transducin. The polypeptide also serves as a substrate for ADP-ribosylation by cholera and pertussis toxins. The ability of the 40-kDa polypeptide to serve as substrate for the toxin-mediated ribosylation is mediated by blue-light irradiation, implying that the 40-kDa polypeptide is the alpha subunit of a blue light-stimulated G protein. The 40-kDa polypeptide binds a nonhydrolyzable photoaffinity-labeling analog of GTP only after irradiation with blue light. The protein we have described may function as an alpha subunit of a G protein active in the process of light-mediated development in higher plants. PMID- 1924353 TI - Binding of Bacillus thuringiensis proteins to a laboratory-selected line of Heliothis virescens. AB - A laboratory-selected colony of Heliothis virescens displaying a 20- to 70-fold level of resistance to Bacillus thuringiensis proteins was evaluated to identify mechanism(s) of resistance. Brush-border membrane vesicles were isolated from larval midgut epithelium from the susceptible and resistant strains of H. virescens. Two B. thuringiensis proteins, CryIA(b) and CryIA(c), were iodinated and shown to specifically bind to brush-border membrane vesicles of both insect strains. Multiple changes in the receptor-binding parameters were seen in the resistant strain as compared with the susceptible strain. A 2- to 4-fold reduction in binding affinity was accompanied by a 4- to 6-fold increase in binding-site concentration for both proteins. Although these two B. thuringiensis proteins competed for the same high-affinity binding site, competition experiments revealed different receptor specificity toward these proteins in the resistant H. virescens line. The H. virescens strains were not sensitive to a coleopteran-active protein, CryIIIA, nor did these proteins compete with the CryIA proteins for binding. Complexity of the mechanism of resistance is consistent with the complex mode of action of B. thuringiensis proteins. PMID- 1924354 TI - Posttranslational modification of Ha-ras p21 by farnesyl versus geranylgeranyl isoprenoids is determined by the COOH-terminal amino acid. AB - ras proteins undergo posttranslational modification by a 15-carbon farnesyl isoprenoid at a cysteine within a defined COOH-terminal amino acid motif; i.e., Cys-Ali-Ali-Ser/Met (where Ali represents an aliphatic residue). In other low molecular mass GTP-binding proteins, cysteines are modified by 20-carbon geranylgeranyl groups within a Cys-Ali-Ali-Leu motif. We changed the terminal Ser 189 of Ha-ras p21 to Leu-189 by site-directed mutagenesis and found that the protein was modified by [3H]geranylgeranyl instead of [3H]farnesyl in an in vitro assay. Gel-permeation chromatography of [3H]mevalonate-labeled hydrocarbons released from immunoprecipitated ras proteins overexpressed in COS cells indicated that Ha-ras p21(Leu-189) was also a substrate for 20-carbon isoprenyl modification in vivo. Additional steps in Ha-ras p21 processing, normally initiated by farnesylation, appear to be supported by geranylgeranylation, based on metabolic labeling of Ha-ras p21(Leu-189) with [3H]palmitate and its subcellular localization in a particulate fraction from COS cells. These observations indicate that the amino acid occupying the terminal position (Xaa) in the Cys-Ali-Ali-Xaa motif constitutes a key structural feature by which Ha-ras p21 and other proteins with ras-like COOH-terminal isoprenylation sites are distinguished as substrates for farnesyl- or geranylgeranyltransferases. PMID- 1924355 TI - X/Y translocations resulting from recombination between homologous sequences on Xp and Yq. AB - Several regions of sequence homology between the human X and Y chromosomes have been identified. These segments are thought to represent areas of these chromosomes that have engaged in meiotic recombination in relatively recent evolutionary times. Normally, the X and Y chromosomes pair during meiosis and exchange DNA only within the pseudoautosomal region at the distal short arms of both chromosomes. However, it has been suggested that aberrant recombination involving other segments of high homology could be responsible for the production of X/Y translocations. We have studied four X/Y translocation patients using molecular probes detecting homologous sequences on X and Y chromosomes. In one translocation the breakpoints have been isolated and sequenced. The mapping data are consistent with the hypothesis that X/Y translocations arise by homologous recombination. The sequencing data from one translocation demonstrate this directly. PMID- 1924356 TI - Catalysis by cytochrome P-450 of an oxidative reaction in xenobiotic aldehyde metabolism: deformylation with olefin formation. AB - As we have briefly described elsewhere, cytochrome P-450 catalyzes the oxidative deformylation of cyclohexane carboxaldehyde to yield cyclohexene and formic acid in a reaction believed to involve a peroxyhemiacetal-like adduct formed between the substrate and molecular oxygen-derived hydrogen peroxide. This reaction is a useful model for the demethylation reactions catalyzed by the steroidogenic P 450s, aromatase, and lanosterol demethylase. In the present study, the cytochrome P-450-catalyzed formation of olefinic products from a series of xenobiotic aldehydes has been demonstrated. Isobutyraldehyde and trimethylacetaldehyde, but not propionaldehyde, are converted to the predicted olefinic products, suggesting a requirement for branching at the alpha carbon. In addition, the four C5 aldehydes of similar hydrophobicity were compared for their ability to undergo the reaction. The straight-chain valeraldehyde gave no olefinic products with five different rabbit liver microsomal P-450 isozymes. However, increasing activity was seen with the other isomers in the order of isovaleraldehyde, 2 methylbutyraldehyde, and trimethylacetaldehyde, with all of the P-450 cytochromes. The catalytic rate with trimethylacetaldehyde is highest with antibiotic-inducible P-450 form 3A6, followed by phenobarbital-inducible form 2B4 and ethanol-inducible form 2E1. Citronellal, a beta-branched aldehyde that is found in many essential oils and is widely used as an odorant and a flavorant, was found to undergo the oxidative deformylation reaction to yield 2,6-dimethyl 1,5-heptadiene, but only with P-450 2B4. The oxidative cleavage reaction with olefin formation appears to be widespread, as judged by the variety of aldehydes that serve as substrates and of P-450 cytochromes that serve as catalysts. PMID- 1924357 TI - Sindbis virus RNA polymerase is degraded by the N-end rule pathway. AB - Upon infection of animal cells by Sindbis virus, four nonstructural (ns) proteins, termed nsP1-4 in order from 5' to 3' in the genome, are produced by posttranslational cleavage of a polyprotein. nsP4 is believed to function as the viral RNA polymerase and is short-lived in infected cells. We show here that nsP4 produced in reticulocyte lysates is degraded by the N-end rule pathway, one ubiquitin-dependent proteolytic pathway. When the N-terminal residue of nsP4 is changed by mutagenesis, the metabolic stabilities of the mutant nsP4s follow the N-end rule, in that the half-life of nsP4 bearing different N-terminal residues decreases in the order Met greater than Ala greater than Tyr greater than or equal to Phe greater than Agr. Addition of dipeptides Tyr-Ala, Trp-Ala, or Phe Ala to the translation mixture inhibits degradation of Tyr-nsP4 and Phe-nsP4, but not of Arg-nsP4. Conversely, dipeptides His-Ala, Arg-Ala, and Lys-Ala inhibit the degradation of Arg-nsP4 but not of Tyr-nsP4 or Phe-nsP4. We found that there is no lysine in the first 43 residues of nsP4 that is required for its degradation, indicating that a more distal lysine functions as the ubiquitin acceptor. Strict control of nsP4 concentration appears to be an important aspect of the virus life cycle, since the concentration of nsP4 in infected cells is regulated at three levels: translation of nsP4 requires read-through of an opal termination codon such that it is underproduced; differential processing by the virus-encoded proteinase results in temporal regulation of nsP4; and nsP4 itself is a short lived protein degraded by the ubiquitin-dependent N-end rule pathway. PMID- 1924358 TI - Rapid and efficient purification of native histidine-tagged protein expressed by recombinant vaccinia virus. AB - Vaccinia virus has been used as a vector to express foreign genes for the production of functional and posttranslationally modified proteins. A procedure is described here that allows the rapid native purification of vaccinia-expressed proteins fused to an amino-terminal tag of six histidines. Extracts from cells infected with recombinant vaccinia virus are loaded onto Ni2+.nitrilotriacetic acid (Ni2+.NTA)-agarose and histidine-tagged proteins are selectively eluted with imidazole-containing buffers. In the case of the human serum response factor (SRF), a transcription factor involved in the regulation of the c-fos protooncogene, the vaccinia-expressed histidine-tagged SRF (SRF-6His) could be purified solely by this step to greater than 95% purity. SRF-6His was shown to resemble authentic SRF by functional criteria: it was transported to the nucleus, bound specifically the c-fos serum response element, interacted with the p62TCF protein to form a ternary complex, and stimulated in vitro transcription from the serum response element. Thus, the combination of vaccinia virus expression and affinity purification by Ni2+.NTA chromatography promises to be useful for the production of proteins in a functional and posttranslationally modified form. PMID- 1924359 TI - Autoregulation of human thymidylate synthase messenger RNA translation by thymidylate synthase. AB - Thymidylate synthase (TS; 5,10-methylenetetrahydrofolate:dUMP C methyltransferase, EC 2.1.1.45) is essential for the de novo synthesis of thymidylate, a precursor of DNA. Previous studies have shown that the cellular level of this protein is regulated at both the transcriptional and posttranscriptional levels. The regulation of human TS mRNA translation was studied in vitro with a rabbit reticulocyte lysate system. The addition of purified human recombinant TS protein to in vitro translation reactions inhibited translation of TS mRNA. This inhibition was specific in that recombinant TS protein had no effect on the in vitro translation of mRNA for human chromogranin A, human folate receptor, preplacental lactogen, or total yeast RNA. The inclusion of dUMP, 5-fluoro-dUMP, or 5,10-methylene-tetrahydrofolate in in vitro translation reactions completely relieved the inhibition of TS mRNA translation by TS protein. Gel retardation assays confirmed a specific interaction between TS protein and its corresponding mRNA but not with unrelated mRNAs, including human placenta, human beta-actin, and yeast tRNA. These studies suggest that translation of TS mRNA is controlled by its own protein end product, TS, in an autoregulatory manner. PMID- 1924360 TI - Involvement of wild-type p53 in pre-B-cell differentiation in vitro. AB - Wild-type p53 protein is a growth modulator whose inactivation has been found to be a key event in malignant transformation. Reconstitution of wild-type p53 in the p53-nonproducer, Abelson murine leukemia virus-transformed pre-B-cell line L12 gave rise to stably growing clones. Wild-type p53-producer derived cell lines exhibit an altered cell cycle, however. More cells with an extended G0/G1 phase were found than in the p53-nonproducer parental cell line. Furthermore, when injected into syngeneic mice, these cells induced a lower incidence of tumors and these tumors were less aggressive. Analysis of immunoglobulin expression revealed that wild-type p53 induced the expression of cytoplasmic immunoglobulin mu heavy chain. In addition, these derived cells lines exhibited increased levels of a B cell-specific surface marker, B220. These results suggest that wild-type p53 may function as a cell differentiation factor that can induce development of pre-B cells into a more advanced stage in the pathway of B-cell maturation. In these pre-B cells, wild-type p53 may induce cell differentiation without terminal growth arrest of the cell population. PMID- 1924361 TI - Alteration from T- to B-cell tropism reduces thymic atrophy and cytocidal effects in thymocytes but not neurovirulence induced by ts1, a mutant of Moloney murine leukemia virus TB. AB - The ts1 mutant of Moloney murine leukemia virus TB causes degenerative neurologic and immunologic disease in mice, characterized by development of spongiform encephalomyelopathy resulting in hindlimb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. To investigate the pathogenesis of the thymic atrophy caused by ts1, we constructed a chimeric virus, ts1-Cas(NS), in which a major portion of the U3 region of the long terminal repeat of ts1, a T-lymphotropic and neurovirulent murine leukemia virus, was replaced by the corresponding U3 region of Cas-Br-E, a B-lymphotropic and neurovirulent murine leukemia virus. In FVB/N mice, ts1-Cas(NS) induced paralytic and wasting disease with incidence, severity, and latency similar to that induced by ts1, but it failed to cause thymic atrophy as severe as that observed in ts1 infected mice. Furthermore, thymocytes cultured from ts1-Cas(NS)-infected mice died at a much slower rate than those of ts1-infected mice. The U3 substitution in ts1-Cas(NS) specifically diminished the ability of the virus to replicate in the thymus, whereas viral replication in the spinal cord was not significantly affected; thus, neurovirulence was not changed. The correlation of reduced thymic atrophy with decreased thymic viral titers and the decreased ability of ts1 Cas(NS) to cause thymocyte death in mice suggest strongly that the marked thymic atrophy in ts1-infected mice is not an indirect effect occurring secondary to neurodegenerative and wasting disease but is a direct cytopathic effect of high level viral replication in the thymus. PMID- 1924362 TI - Human auditory evoked gamma-band magnetic fields. AB - We have discovered a ca. 40-Hz transient magnetic oscillatory response, evoked in the human brain by the onset of auditory stimuli, consisting of four or more cycles locked in phase to stimulus onset in approximately the 20- to 130-ms poststimulus interval. The response originates in the supratemporal auditory cortex, some millimeters deeper and anterior to the source of the larger amplitude slow-wave M100 component of the evoked magnetic field and moves in a posterior arcing trajectory 1 cm or more in length. The oscillatory cortical activation elicited by auditory stimuli may be similar to the gamma-band cortical oscillations elicited by olfactory and visual stimuli and may represent an essential component of auditory perceptual processing. PMID- 1924363 TI - A region of the Ada DNA-repair protein required for the activation of ada transcription is not necessary for activation of alkA. AB - The adaptive response of Escherichia coli protects cells against the mutagenic and toxic effects of alkylating agents. This response is controlled by the Ada protein, which not only functions as the transcriptional activator of the ada and alkA genes but also possesses two DNA methyltransferae activities. Ada is converted into an efficient transcriptional activator by transferring a methyl group from a DNA methylphosphotriester to its own Cys-69 residue and then binds to a DNA sequence (the Ada box) present in both the ada and alkA promoters. Although the Ada protein initially appeared to regulate the ada and alkA genes in a similar fashion, our studies show that the wild-type Ada protein and its truncated derivatives can differentially regulate ada and alkA transcription. In vivo, lower levels of wild-type methylated Ada are needed to activate ada transcription than alkA transcription. In cells exposed to alkylating agents, the N-terminal half of Ada, which contains the DNA-binding domain, is sufficient for efficient activation of alkA, but not ada, transcription. Moreover, truncated derivatives containing 80-90% of Ada are extremely strong constitutive activators of ada but are only inducible activators of alkA transcription. These results suggest that the mechanism by which Ada activates ada transcription differs from that by which it activates alkA transcription. PMID- 1924364 TI - Antiparallel plasmid-plasmid pairing may control P1 plasmid replication. AB - The copy number of the P1 plasmid replicon is stringently controlled, giving only one or two copies per newborn cell. Control is achieved by the action of the copy control locus incA, which contains nine repeats of the 19-basepair binding site for the plasmid-encoded initiator protein RepA. A set of five similar repeats are present in the replication origin where RepA acts to trigger initiation. Using an in vitro replication system consisting of an Escherichia coli extract, the P1 origin as a template, and purified RepA protein, we show that supercoiled DNA circles containing the incA locus block origin function in trans. Shutdown becomes complete at a 1:1 ratio of origin to incA sequences. This is not due to titration of the RepA protein, as an excess of RepA can be added without restoring activity. Rather, the incA sequences appear to block the origin by direct contact in a plasmid-plasmid pairing event. When both the origin and the incA locus are present on one plasmid, trans contacts with daughter molecules appear to predominate over cis looping. The results are consistent with a model for replication control where daughter plasmids block their own replication by a pairing in which each origin is in contact with the incA locus of its partner. PMID- 1924365 TI - Reversal of synaptic depression by serotonin at Aplysia sensory neuron synapses involves activation of adenylyl cyclase. AB - Facilitation of the monosynaptic connection between siphon sensory neurons and gill and siphon motor neuron contributes to sensitization and dishabituation of the gill and siphon withdrawal reflex in Aplysia. The facilitatory transmitter serotonin (5-HT) initiates two mechanisms that act in parallel to increase transmitter release from siphon sensory neurons. 5-HT acts, at least partly through cAMP, to broaden the presynaptic action potential. 5-HT also initiates a second process that facilitates depressed sensory neuron synapses by a mechanism independent of changes in action potential duration. Recent experiments indicated that either of two protein kinases, cAMP-dependent protein kinase A and protein kinase C, are capable of effectively activating this second facilitatory mechanism, restoring synaptic transmission in depressed synapses. We have used the adenylyl cyclase inhibitor SQ 22,536 [9-(tetrahydro-2-furyl)adenine or THFA] to explore the contribution of cAMP to the reversal of synaptic depression. THFA effectively inhibited both adenylyl cyclase activity in vitro and known cyclase mediated effects in intact sensory neurons. THFA also completely blocked facilitation of depressed synapses by 5-HT. These results suggest that adenylyl cyclase plays a critical role in the reversal of synaptic depression that contributes to dishabituation in this system. PMID- 1924366 TI - Inhibition of sleep in rats by inorganic selenium compounds, inhibitors of prostaglandin D synthase. AB - Prostaglandin (PG) D2 has been postulated to be an endogenous sleep-promoting factor in rats, and SeCl4 and Na2SeO3 recently have been shown to inhibit the PGD synthase (prostaglandin-H2 D-isomerase, EC 5.3.99.2) activity of rat brain. The effect of these selenium compounds on sleep-wake activities was examined in freely moving rats along with their effects on brain temperature, food and water intake, and behavior. Test substances were administered for 6 hr into the third ventricle of rats, using a microdialysis technique. SeCl4, time- and dose dependently, inhibited sleep at perfusion rates of 60 pmol/0.2 microliter per min and higher, and the inhibition was almost complete at rates greater than 200 pmol/0.2 microliter per min. The effect was reversible and was followed by a rebound. Na2SeO3 exhibited similar effects, but Na2SO3 did not show any effect on sleep. Simultaneous administration of dithiothreitol eliminated the sleep inhibiting effects of these selenium compounds. These findings indicate that the decrease in sleep is due to inhibition of the PGD synthase activity in the brain by SeCl4 as well as Na2SeO3. During the inhibition of sleep, the rats in general showed an activation of behavior with moderate elevation of brain temperature and a detectable increase in food and water intake, suggesting that the sleep inhibited state of the rats was similar to the physiological state of wakefulness and that the inhibitory effect was not due to the general toxicity of selenium. PMID- 1924367 TI - Origin of human chromosome 2: an ancestral telomere-telomere fusion. AB - We have identified two allelic genomic cosmids from human chromosome 2, c8.1 and c29B, each containing two inverted arrays of the vertebrate telomeric repeat in a head-to-head arrangement, 5'(TTAGGG)n-(CCCTAA)m3'. Sequences flanking this telomeric repeat are characteristic of present-day human pretelomeres. BAL-31 nuclease experiments with yeast artificial chromosome clones of human telomeres and fluorescence in situ hybridization reveal that sequences flanking these inverted repeats hybridize both to band 2q13 and to different, but overlapping, subsets of human chromosome ends. We conclude that the locus cloned in cosmids c8.1 and c29B is the relic of an ancient telomere-telomere fusion and marks the point at which two ancestral ape chromosomes fused to give rise to human chromosome 2. PMID- 1924369 TI - The human homologous pairing protein HPP-1 is specifically stimulated by the cognate single-stranded binding protein hRP-A. AB - Homologous pairing and strand exchange of DNA are catalyzed by the human homologous pairing protein HPP-1 in a magnesium-dependent, ATP-independent reaction that requires homologous DNA substrates and stoichiometric quantities of HPP-1. Here we show that the addition of the purified human single-strand binding (SSB) protein hRP-A to the reaction mixture stimulates the rate of homologous pairing 70-fold and reduces the amount of HPP-1 required for the reaction at least 10-fold. The identification of hRP-A as a stimulatory factor of HPP-1 catalyzed reaction was facilitated by its recognition as a member of a high molecular weight complex of recombination components. Neither the Escherichia coli SSB protein, bacteriophage T4 gene 32 protein, nor the highly conserved Saccharomyces cerevisiae yRP-A SSB protein could substitute for hRP-A in this stimulation. Because only the cognate SSB was capable of stimulating HPP-1, these results suggest that eukaryotes depend on unique and specific interactions between DNA recombination components. PMID- 1924368 TI - RNase-like domain in DNA-directed RNA polymerase II. AB - DNA-directed RNA polymerase is responsible for gene expression. Despite its importance, many details of its function and higher-order structure still remain unknown. We report here a local sequence similarity between the second largest subunit of RNA polymerase II and bacterial RNases Ba (barnase), Bi, and St. The most remarkable similarity is that the catalytic sites of the RNases are shared with the eukaryotic RNA polymerase II subunits of Drosophila melanogaster and Saccharomyces cerevisiae. Several amino acids conserved among the RNases and the RNase-like domains of the RNA polymerase subunits are located in the neighborhood of the catalytic sites of barnase, whose three-dimensional structure has been resolved. This observation suggests the functional importance of the RNase-like domain of the RNA polymerase subunits and indicates that the RNase-like domain may have RNase activity. The location of the RNase-like domain relative to the region necessary for RNA polymerization is similar to the relative proximity of 5'----3' or 3'----5' exonuclease and the region of polymerase activity of DNA polymerase I. The RNase-like domain might work in proofreading, as in RNA directed RNA polymerase of influenza virus, or it may contribute to RNA binding through an unknown function. PMID- 1924370 TI - Site-specific effect of thymine dimer formation on dAn.dTn tract bending and its biological implications. AB - dAn.dTn sequences, otherwise known as A tracts, are hotspots for cis-syn thymine dimer formation and deletion mutations induced by UV light. Such A tracts are also known to bend DNA, suggesting that some biological effects of UV light might be related to the distinctive structure and properties of cis-syn dimer containing A tracts. To investigate the effect of thymine dimer formation on A tract bending multimers of all possible dimer monoadducts of a dA6.dT6-containing decamer known to bend DNA were prepared along with multimers of a dimer containing 21-mer of heterogeneous sequence. The characteristic anomalous electrophoretic behavior of the phased A-tract multimers was essentially abolished by dimer formation at the center of the A tract and was only slightly reduced by dimer formation at the ends. These effects are attributed to disruption of the A-tract structure at the site of the dimer, resulting in intact A tracts of reduced length and, hence, reduced bending. This model was suggested by the ability to formulate the estimated bend angles of the dimer-containing A tracts as approximately equal to the sum of the bend angles induced by the dimer and the remaining intact portion of the A tract. Contrary to a previous experimental study that concluded that the thymine dimer bends DNA by approximately 30 degrees, the dimer was determined to bend DNA by only approximately 7 degrees. Reduction of the bending of a DNA sequence by dimer formation may have a number of unpredicted and important biological consequences. PMID- 1924371 TI - Phylogenetic and functional affinities of Babakotia (primates), a fossil lemur from northern Madagascar. AB - Recent paleontological expeditions to the Ankarana range of northern Madagascar have recovered the partial remains of four individuals of a newly recognized extinct lemur, Babakotia radofilai. Craniodental and postcranial material serve to identify Babakotia as a member of the palaeopropithecids (also including the extinct genera Palaeopropithecus, Archaeoindris, and Mesopropithecus). Living indrids form the sister group to this fossil clade. The postcranial anatomy indicates that Babakotia was a medium-sized (approximately 15 kg) indroid whose inferred positional behaviors were primarily slow climbing and hanging. Although it is probable that a leaping component typified the ancestral positional repertoire of all Malagasy lemurs, the mosaic nature of the locomotor skeleton of Babakotia further suggests that vertical climbing and hang-feeding rather than ricochetal leaping were primitive for indrids and palaeopropithecids and that the dramatic saltatory adaptations of the living indrids postdate the divergence of these two lineages. PMID- 1924372 TI - Sequence effects on local DNA topology. AB - Nuclear Overhauser effect-derived distances between adenine H2 protons and anomeric H1' protons on the same strand or on the complementary strand are presented for several different DNA duplexes. The cross-strand (n)AH2 to (m + 1)H1' distances [designated as x, where (n) and (m) are complementary residues] vary by up to 1 A depending on the sequence. In all possible A-containing pyrimidine-purine steps (CA, TG, and TA), x is greater than 4.5 A. In GA steps, x varies within rather wide limits in the range 3.8-4.5 A, whereas in AA steps the lower limit is 3.7 A and the upper limit is approximately 4.2 A. In purine-purine steps, x is affected by at least three factors: (i) adjacent pyrimidine-purine steps at the 5' end [e.g., YRA sequences (where Y = T or C and R = G or A)], or a pyrimidine-purine step at the 3' end of the pyrimidine-pyrimidine step on the complementary strand, cause x to increase, (ii) an AT step at the 3' end of a purine-purine step (e.g., RAT) causes x to decrease, and (iii) substitution of bases at the next-nearest neighbor position leads to changes in x at GA and AA steps. The latter factor seems to be due to a cooperative effect arising from formation of the "anomalous" B' structure when the substitution produces an AnTm tract (which always produces a decrease in x). The data indicate that (n)AH2-(n + 1)H1' distances on the same strand (designated as s) are also sequence dependent. Thus on AA steps, neighboring substitutions produce the same effect on s as on the cross-strand x distances. The results lead to the ability to predict changes in AH2-H1' distances depending on the DNA sequence. By using high-resolution x ray B-type structures as a set of allowable B conformations, a very good correlation was found between x and the minor groove width parameters P-P or H1' H1'. Thus, the x distances are a direct probe of the minor groove width in B-type DNA, and changes in this distance therefore reflect changes in the minor groove width. Since many of the sequences studied are sites of protein recognition, the observed sequence-structure dependence in DNA probably plays an important role in the process of recognition by proteins and minor groove ligands such as drugs. PMID- 1924373 TI - The Bacillus subtilis sigL gene encodes an equivalent of sigma 54 from gram negative bacteria. AB - The levanase operon in Bacillus subtilis is expressed from a -12, -24 promoter and transcription is stimulated by the regulator LevR, which contains a domain homologous with the central domain of the NifA and NtrC family of regulators. We isolated mutants defective in the expression of the levanase operon. These strains contain mutations that define a gene, called sigL, located between cysB and sacB on the genetic map. The sigL gene was cloned and sequenced. It encodes a polypeptide containing 436 residues with a molecular weight of 49,644. The amino acid sequence of SigL is homologous with all sigma 54 factors from Gram-negative bacteria, including Rhizobium meliloti (32% identity) and Klebsiella pneumoniae (30% identity). B. subtilis sigL mutants have a pleiotropic phenotype: (i) the transcription of the levanase operon is strongly reduced and (ii) in minimal medium lacking ammonia, sigL mutants cannot grow when arginine, ornithine, isoleucine, or valine is the sole nitrogen source. These results indicate that the sigL gene encodes an equivalent of the sigma 54 factor in B. subtilis, to our knowledge, the first of this type to be identified in Gram-positive bacteria. PMID- 1924374 TI - Biochemical characterization of murine glycosylation-inhibiting factor. AB - The glycosylation-inhibiting factor (GIF) was isolated from serum-free culture supernatants of the murine T-cell hybridoma, 231F1 cells, by using an immunosorbent coupled with the monoclonal anti-lipomodulin antibody. The isolated lymphokine is a 14-kDa protein with a pI of 5.5, as determined by SDS/PAGE and two-dimensional gel electrophoresis. Fractionation of a mixture of radiolabeled GIF with culture supernatant of the 231F1 cells on ion-exchange and reverse-phase columns and by gel filtration demonstrated homogeneity of the 14-kDa GIF and confirmed that the bioactivity of GIF and the antigenic determinant recognized by the monoclonal anti-GIF antibody are associated with the 14-kDa protein. The 125I labeled 14-kDa protein binds to the murine T-cell hybridoma 12H5 cells, which have been used for bioassay of GIF, and the murine B-cell line A20.3 cells, but the binding of the protein to resting murine splenic lymphocytes was barely detectable. Under the same experimental conditions, binding of the 125I-labeled recombinant human lipocortin I to the 12H5 cells was not detectable. In contrast, the 125I-labeled lipocortin, but not the 14-kDa GIF, bound to phosphatidylserine vesicles. The results indicate that GIF does not belong to the anexin family. PMID- 1924376 TI - Direct physiological evidence for scene segmentation by temporal coding. AB - Theoretical studies have suggested that scene segmentation may be accomplished by a temporal coding mechanism using synchronization of neuronal responses. Here we report a direct experimental test of this hypothesis. Neuronal responses were recorded simultaneously from two to four sites with overlapping receptive fields in cat visual cortex. Correlation analysis revealed that all cells synchronized their responses irrespective of their orientation preference when they were activated by a single light bar. However, when stimulated with two superimposed light bars of different orientations, the same cells segregated into distinct assemblies according to their orientation preferences. Within each of these assemblies responses were synchronized, but correlation was absent between the two assemblies. These results are compatible with the hypothesis that responses to individual objects in a scene are distinguished by synchrony, whereas responses to different objects show no temporal correlation, thus allowing for the segmentation of superimposed stimuli. We conclude that stimulus-specific synchronization of spatially distributed neuronal responses may provide a physiological mechanism for scene segmentation. PMID- 1924375 TI - Cloning and characterization of a 3-methyladenine DNA glycosylase cDNA from human cells whose gene maps to chromosome 16. AB - We described previously the isolation of a Saccharomyces cerevisiae 3 methyladenine (3-MeAde) DNA glycosylase repair gene (MAG) by its expression in glycosylase-deficient Escherichia coli alkA tag mutant cells and its ability to rescue these cells from the toxic effects of alkylating agents. Here we extend this cross-species functional complementation approach to the isolation of a full length human 3-MeAde DNA glycosylase cDNA that rescues alkA tag E. coli from killing by methyl methanesulfonate, and we have mapped the gene to human chromosome 16. The cloned cDNA, expressed from the pBR322 beta-lactamase promoter, contains an 894-base-pair open reading frame encoding a 32,894-Da protein able to release 3-MeAde, but not 7-methylguanine, from alkylated DNA. Surprisingly, the predicted human protein does not share significant amino acid sequence homology with the bacterial AlkA and Tag glycosylases or the yeast MAG glycosylase, but it does share extensive amino acid sequence homology with a rat 3-MeAde DNA glycosylase and significant DNA sequence homology with genes from several mammalian species. The cloning of a human 3-MeAde DNA glycosylase cDNA represents a key step in generating 3-MeAde repair-deficient cells and the determination of the in vivo role of this DNA repair enzyme in protecting against the toxic and carcinogenic effects of alkylating agents. PMID- 1924377 TI - Attractive and repulsive interactions between and within adsorbed ribonuclease A layers. AB - Adsorbed layers of pancreatic RNase A on molecularly smooth mica in aqueous solution attract inorganic mica surfaces whereas they repel similarly adsorbed RNase A layers. As the clean mica surface is covered with RNase A, the attractive interaction slowly diminishes with time and eventually converts to a purely repulsive interaction. Solvent is squeezed out of the solution in the gap during compression of the two surfaces so that the adsorbed protein concentration, as measured directly by the refractive index, increases significantly. The kinetics of this process is analyzed using surface force-distance measurements. All these results are predicted for constrained equilibrium by a discrete lattice model [Scheutjens, J. M. H. M. & Fleer, G. J. (1985) Macromolecules 18, 1882-1900]. Reasonable values are obtained for the constants of the model. We also report on the equilibrium behavior and interaction of densely adsorbed RNase A layers in aqueous solutions of varying ionic strength and pH. With increasing ionic strength, intramolecular forces dominate with diminished electrostatic repulsion. Thus, the adsorbed protein layer becomes more compact while unattached protein molecules coil and fold, making them less likely to form strong intermolecular bridges. Only at very low ionic strength (0.1 mM KCl), when electrostatic forces dominate, does the membrane potential model come close to predicting the long distance repulsive behavior. Thus, at higher ionic strengths, other non electrostatic interactions (such as hydrophobic interactions) possibly dominate. An increase in the pH of the solution from 5 to 9.2, the pI of RNase A, significantly reduces the electrostatic repulsion between protein molecules in favor of hydrophobic attractive interactions. This results in lower short-range steric repulsion. However, in contrast to the ionic-strength effect, an increased long-range repulsive force with a much longer decay length is observed. This may be due to contaminants such as DNase that have their pI at a pH other than 9.2. Thus, as with the changing-ionic-strength study, thinner and denser adsorbed layers are formed. Finally, for the kinetic studies, two characteristic length scales--the thickness of the adsorbed layer and the "jump-in" distance--vary linearly with the square root of time. This is consistent with our earlier results and once again implies a diffusion-driven process. PMID- 1924378 TI - Electrostatic control of midpoint potentials in the cytochrome subunit of the Rhodopseudomonas viridis reaction center. AB - The photosynthetic reaction center of Rhodopseudomonas viridis has four hemes in a linear arrangement with alternating high- and low-potential sites. Their midpoints are -60, 20, 310, and 380 mV [Dracheva, S. M., Drachev, L. A., Konstantinov, A. A., Semenov, A. Y., Skulachev, V. P., Arutjunjan, A. M., Shuvalov, V. A. & Zaberezhnaya, S. M. (1988) Eur. J. Biochem. 171, 253-264]. Electrostatic calculations reproduce the 440-mV midpoint spread and assignments of high- and low-potential hemes. When calculations on model compounds to connect the theoretical midpoints to the standard hydrogen electrode are used, the absolute electrochemical midpoints for the reaction center hemes are also in good agreement with experiment. The free energy of oxidation is found to be dependent on pairwise interactions with charged amino acids, heme propionic acids, previously oxidized hemes, and axial ligands and on the reaction field induced by heme oxidation. PMID- 1924380 TI - Antigenic variation in Plasmodium falciparum. AB - Antigenic variation of infectious organisms is a major factor in evasion of the host immune response. However, there has been no definitive demonstration of this phenomenon in the malaria parasite Plasmodium falciparum. In this study, cloned parasites were examined serologically and biochemically for the expression of erythrocyte surface antigens. A cloned line of P. falciparum gave rise to progeny that expressed antigenically distinct forms of an erythrocyte surface antigen but were otherwise identical. This demonstrates that antigenic differences on the surface of P. falciparum-infected erythrocytes can arise by antigenic variation of clonal parasite populations. The antigenic differences were shown to result from antigenic variation of the parasite-encoded protein, the P. falciparum erythrocyte membrane protein 1. PMID- 1924379 TI - The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. AB - The cytoplasmic region of the Ca(2+)-dependent cell-adhesion molecule (CAM) uvomorulin associates with distinct cytoplasmic proteins with molecular masses of 102, 88, and 80 kDa termed alpha, beta, and gamma catenin, respectively. This complex formation links uvomorulin to the actin filament network, which seems to be of primary importance for its cell-adhesion properties. We show here that antibodies against alpha catenin also immunoprecipitate complexes that contain human N-cadherin, mouse P-cadherin, chicken A-CAM (adherens junction-specific CAM; also called N-cadherin) or Xenopus U-cadherin, demonstrating that alpha catenin is complexed with other cadherins. In immunofluorescence tests, alpha catenin is colocalized with cadherins at the plasma membrane. However, in cadherin-negative Ltk- cells, alpha catenin is found uniformly distributed in the cytoplasm, suggesting some additional biological function(s). Expression of uvomorulin in these cells results in a concentration of alpha catenin at membrane areas of cell contacts. We also have cloned and sequenced murine alpha catenin. The deduced amino acid sequence reveals a significant homology to vinculin. Our results suggest the possibility of a new vinculin-related protein family involved in the cytoplasmic anchorage of cell-cell and cell-substrate adhesion molecules. PMID- 1924381 TI - Heterotropic interactions in aspartate transcarbamoylase: turning allosteric ATP activation into inhibition as a consequence of a single tyrosine to phenylalanine mutation. AB - Aspartate transcarbamoylase (EC 2.1.3.2) is extensively studied as a model for cooperativity and allostery. This enzyme shows cooperativity between the catalytic sites, and its activity is feedback inhibited by CTP and activated by ATP. These regulatory processes involve several interfaces between catalytic and regulatory chains as well as between domains within these two types of chains. As far as the regulatory chain is concerned, its two domains are in contact through a hydrophobic interface, in which a tyrosine residue is inserted in a pocket involving two leucine residues of the allosteric domain and a valine and a leucine residue of the zinc domain. To probe the possible implication of this hydrophobic core in the CTP and ATP regulatory effect, the tyrosine was replaced by a phenylalanine through oligonucleotide-directed mutagenesis. Interestingly, the resulting mutant shows a complete inversion of the ATP effect; it is now inhibited by ATP instead of being activated by this nucleotide triphosphate. This mutant remains normally sensitive to the feedback inhibitor CTP. This result shows that the hydrophobic interface between the two domains of the regulatory chain plays an important role in the discrimination between the regulatory signals promoted by the two allosteric effectors. PMID- 1924382 TI - Alanine scanning site-directed mutagenesis of the zinc fingers of transcription factor ADR1: residues that contact DNA and that transactivate. AB - To identify functionally important amino acids in the two zinc fingers of transcription factor ADR1 [alcohol dehydrogenase (ADH) II synthesis regulator], oligonucleotide-directed mutagenesis was used to substitute alanine for the original amino acid at each position in both fingers. The effects of these mutations on DNA binding and thermal stability of ADR1 in vitro and on activation of ADH2 expression in vivo were measured. The DNA binding activity was remarkably heatstable. Amino acids that are candidates for DNA contact sites were identified in the finger-tip and alpha-helical region of each finger, three in the first finger and two in the second. Unexpectedly, an acidic residue in the first finger was essential for transactivation, but its replacement by alanine had no effect on DNA binding. Substitution at several highly conserved positions did not affect ADR1 functions. The ADR1 zinc fingers appear to make relatively few energetically significant contacts to DNA, perhaps as few as three in the first finger and one in the second. PMID- 1924383 TI - The LIM region of a presumptive Caenorhabditis elegans transcription factor is an iron-sulfur- and zinc-containing metallodomain. AB - The cysteine-rich LIM motif is highly conserved between invertebrates and mammals. This motif shows similarity both to proteins that bind zinc and to ferredoxins, which contain iron-sulfur clusters. Two tandem copies of the LIM motif are found in a number of presumptive transcription factors, including the protein product of the Caenorhabditis elegans cell-lineage gene lin-11. To investigate the possible metal-binding properties of the LIM region of the lin-11 protein, we expressed and purified a 151-amino acid peptide containing the tandem LIM motifs. The purified peptide binds both zinc (two atoms per protein molecule) and iron (as a redox-active iron-sulfur cluster, with four atoms of iron and four atoms of inorganic sulfide per protein molecule). These observations suggest that the LIM motif is a metallodomain that might function in a redox-sensitive regulation of transcription. PMID- 1924384 TI - Drosophila 60A gene, another transforming growth factor beta family member, is closely related to human bone morphogenetic proteins. AB - The 60A gene, a member of the transforming growth factor beta superfamily of signaling proteins, has been identified in Drosophila melanogaster. From its inferred protein sequence we predict the precursor is secreted and processed to release a growth factor-like molecule. The 60A gene is expressed throughout development with peaks of transcription during early embryogenesis, in pupae, and in adult males. The putative 60A protein shows greater sequence similarity to three vertebrate family members (human bone morphogenetic proteins 5, 6, and 7) than to its only Drosophila relative, the protein product of the decapentaplegic (dpp) gene. This observation suggests that the duplication event that gave rise to the two transforming growth factor beta-like proteins in Drosophila predates the divergence of chordates and arthropods. PMID- 1924385 TI - Pheromonal advertisement of a nuptial gift by a male moth (Utetheisa ornatrix). AB - Male Utetheisa ornatrix produce a courtship pheromone (hydroxydanaidal) that they derive from systemic pyrrolizidine alkaloid of plant origin. Pheromone titers in males correlate with systemic levels of alkaloid and with the quantity of alkaloid transmitted to the female at mating. The male's emission of pheromone during courtship may therefore communicate his possession of protective alkaloids and his capacity to provision the female. By mating preferentially with males endowed with hydroxydanaidal, females may ensure their acquisition of an alkaloidal gift for use in egg defense. PMID- 1924386 TI - A melanocyte-specific gene, Pmel 17, maps near the silver coat color locus on mouse chromosome 10 and is in a syntenic region on human chromosome 12. AB - Melanocytes preferentially express an mRNA species, Pmel 17, whose protein product cross-reacts with anti-tyrosinase antibodies and whose expression correlates with the melanin content. We have now analyzed the deduced protein structure and mapped its chromosomal location in mouse and human. The amino acid sequence deduced from the nucleotide sequence of the Pmel 17 cDNA showed that the protein is composed of 645 amino acids with a molecular weight of 68,600. The Pmel 17 protein contains a putative leader sequence and a potential membrane anchor segment, which indicates that this may be a membrane-associated protein in melanocytes. The deduced protein contains five potential N-glycosylation sites and relatively high levels of serine and threonine. Three repeats of a 26-amino acid motif appear in the middle of the molecule. The human Pmel 17 gene, designated D12S53E, maps to chromosome 12, region 12pter-q21; and the mouse homologue, designated D12S53Eh, maps to the distal region of mouse chromosome 10, a region also known to carry the coat color locus si (silver). PMID- 1924387 TI - Specificity of the murine IgD receptor on T cells is for N-linked glycans on IgD molecules. AB - IgD receptors on murine T cells have been reported in this issue [Tamma, S. M. L., Amin, A. R., Finkelman, F. D., Chen, Y.-W., Thorbecke, G. J. & Coico, R. F. (1991) Proc. Natl. Acad. Sci. USA 88, 9233-9237] to bind either the first or third constant region of the heavy-chain of IgD molecules--findings that could not be satisfactorily explained by IgD amino acid sequences. We now find that boiled IgD molecules or low-Mr fragments from protease-digested IgD still inhibit binding of IgD-coated erythrocytes to IgD receptors. This inhibitory activity can be absorbed with the murine IgD-binding lectin from Griffonia simplicifolia 1 (GS 1) immobilized on Sepharose. N-linked glycans, obtained from N-glycanase-treated IgD and purified by binding to GS-1-Sepharose, also inhibit rosette formation of T-helper cells bearing receptors for IgD with IgD- or mutant IgD-coated erythrocytes. Deglycosylated IgD, produced by treatment with N-glycanase, no longer binds to the lectin and fails to inhibit IgD rosetting. Binding of intact IgD to T cells is also competitively inhibited by N-acetylgalactosamine, galactose, N-acetylglucosamine, and neoglycoproteins containing these sugars. These results clearly show that N-linked glycans, present in both the first and third constant regions of the delta heavy-chain domains, are prerequisites for binding of IgD to IgD receptors. PMID- 1924388 TI - Suppression of H-2b-associated resistance to Friend erythroleukemia virus by a class I gene from the H-2d major histocompatibility complex haplotype. AB - Mice homozygous for the H-2d haplotype at the major histocompatibility complex are markedly more susceptible to erythroleukemia induction by the Friend isolate of murine leukemia retrovirus (FV) than are congenic mice homozygous for the H-2b haplotype. The resistance conferred by the H-2b haplotype is recessive in this cross, since heterozygous F1 mice are as susceptible as parental strain H-2d homozygotes. However, H-2b-associated resistance is not an intrinsically recessive trait, since H-2b/H-2dm1 heterozygotes resemble H-2b homozygotes in their relative resistance to FV; the mutant H-2dm1 haplotype lacks the entire D region of the parental haplotype except for a single class I gene formed by the fusion of its terminal D-region genes to produce a class I gene differing from both parental genes, and thus this finding indicates that one or more D-region genes of the H-2d haplotype can actively suppress H-2b-associated resistance. Unlike H-2dm1, the mutant H-2dm2 haplotype, which retains only the class IDd gene in the D region of the H-2d haplotype, strongly suppresses resistance in H-2b/H 2dm2 heterozygotes, and the presence of Dd as a transgene significantly reduces the resistance of H-2b homozygotes. Since H-2b-associated resistance to FV appears to be due mainly to the capacity of Lb (also called Db), the only class I molecule encoded in the D region of the H-2b haplotype, to present viral epitopes for recognition by FV-specific cytotoxic T lymphocytes, suppression of resistance to FV by the Dd molecule implies that the presence of one class I molecule of the major histocompatibility complex can interfere with either the presentation of viral epitopes by another class I molecule or the generation of T cells that recognize viral epitopes so presented. PMID- 1924389 TI - Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. AB - A human cDNA coding for a protein related to the vascular permeability factor (VPF) was isolated from a term placenta cDNA library; we therefore named its product placenta growth factor (PlGF). PlGF is a 149-amino-acid-long protein and is highly homologous (53% identity) to the platelet-derived growth factor-like region of human VPF. Computer analyses reveal a putative signal peptide and two probable N-glycosylation sites in the PlGF protein, one of which is also conserved in human VPF. By using N-glycosidase F, tunicamycin, and specific antibodies produced in both chicken and rabbit, we demonstrate that PlGF, derived from transfected COS-1 cells, is actually N-glycosylated and secreted into the medium. In addition, PlGF, like VPF, proves to be a dimeric protein. Finally, a conditioned medium from COS-1 cells containing PlGF is capable of stimulating specifically the growth of CPA, a line of endothelial cells, in vitro. PMID- 1924390 TI - Four sites in the acceptor helix and one site in the variable pocket of tRNA(Ala) determine the molecule's acceptor identity. AB - The structural features that determine tRNA(Ala) acceptor identity have been studied with amber-suppressor tRNAs in Escherichia coli cells. Previous work established that a wobble pair composed of guanosine at position 3 and uridine at position 70 (G3-U70) in the acceptor helix of tRNA(Ala) is a determinant of the molecule's acceptor identity. We show that additional determinants are located at three other sites in the acceptor helix and at one site in the variable pocket of tRNA(Ala). These latter determinants are less important than G3.U70 since their individual alterations in mutants of tRNA(Ala) have smaller degrading effects on the functions of the molecules, and subsets of the determinants, when combined with G3.U70, are sufficient to switch the identities of several other tRNAs to that of tRNA(Ala). Other workers are using fragments of the tRNA(Ala) acceptor helix to study the molecule's acceptor identity. Our demonstration that the variable pocket contributes to tRNA(Ala) acceptor identity means that such fragments do not faithfully replicate the structure-function relationship of the cellular process. PMID- 1924392 TI - Importance of purine and pyrimidine content of local nucleotide sequences (six bases long) for evolution of the human immunodeficiency virus type 1. AB - Human immunodeficiency virus type 1 evolves rapidly, and random base change is thought to act as a major factor in this evolution. However, segments of the viral genome differ in their variability: there is the highly variable env gene, particularly hypervariable regions located within env, and, in contrast, the conservative gag and pol genes. Computer analysis of the nucleotide sequences of human immunodeficiency virus type 1 isolates reveals that base substitution in this virus is nonrandom and affected by local nucleotide sequences. Certain local sequences 6 base pairs long are excessively frequent in the hypervariable regions. These sequences exhibit base-substitution hotspots at specific positions in their 6 bases. The hotspots tend to be nonsilent letters of codons in the hypervariable regions--thus leading to marked amino acid substitutions there. Conversely, in the conservative gag and pol genes the hotspots tend to be silent letters because of a difference in codon frame from the hypervariable regions. Furthermore, base substitutions in the local sequences that frequently appear in the conservative genes occurred at a low level, even within the variable env. Thus, despite the high variability of this virus, the conservative genes and their products could be conserved. These may be some of the strategies evolved in human immunodeficiency virus type 1 to allow for positive-selection pressures, such as the host immune system, and negative-selection pressures on the conservative gene products. PMID- 1924391 TI - Germ cell-specific expression of a gene encoding eukaryotic translation elongation factor 1 alpha (eEF-1 alpha) and generation of eEF-1 alpha retropseudogenes in Xenopus laevis. AB - We have studied by in situ hybridization the expression of the genes encoding the somatic form and the oocyte form of Xenopus laevis eEF-1 alpha. The somatic form of eEF-1 alpha (eEF-1 alpha S) mRNA is virtually undetectable in male and female germ cells of the adult gonad but is very abundant in embryonic cells after the neurula stage. In contrast, another form of eEF-1 alpha (eEF-1 alpha O) mRNA is highly concentrated in oogonia and in previtellogenic oocytes but is undetectable in eggs and embryos. eEF-1 alpha O mRNA is also present in spermatogonia and spermatocytes of adult testis. The latter finding identifies eEF-1 alpha O mRNA as a germ cell-specific gene product. Although germ cells contain very little eEF 1 alpha S mRNA, several eEF-1 alpha S retropseudogenes exist in X. laevis chromosomes. These genes are thought to arise in germ cells from reverse transcription of mRNA and subsequent integration of the cDNA copies into chromosomal DNA. We suggest that eEF-1 alpha S pseudogenes are generated in primordial germ cells of the embryo before they differentiate into oogonia or spermatogonia. PMID- 1924393 TI - Monoclonal antibody-targeted superantigens: a different class of anti-tumor agents. AB - The bacterial superantigen staphylococcal enterotoxin (SE) A (SEA) directs cytotoxic T lymphocytes (CTLs) expressing particular sequences of the T-cell receptor (TCR) beta chain to lyse tumor cells expressing major histocompatibility complex (MHC) class II molecules, which serve as receptors for SEs. We now report that chemical conjugates of SEA and the colon carcinoma-reactive monoclonal antibodies (mAbs) C215 or C242 mediate T cell-dependent destruction of colon carcinoma cells lacking MHC class II molecules. SEA was covalently linked to the mAbs C215 and C242 via a PEG-based hydrophilic spacer. The C215-SEA conjugate targeted CD4+ as well as CD8+ CTLs to lyse a panel of colon carcinoma cells lacking MHC class II molecules. T-cell recognition of mAb-SEA conjugates was SEA specific, since SEB-selective T-cell lines with potent cytotoxic activity towards Raji cells coated with SEB did not respond to the C215-SEA conjugate. Unconjugated SEA did not induce T-cell lysis of MHC class II- colon carcinoma cells but efficiently directed CTLs against MHC class II+ Raji cells and certain interferon-treated MHC class II+ colon carcinoma cells. These results suggest that SEA-mAb conjugates retain the SEA-related selectivity for certain TCR beta chain variable region (V beta) sequences but, in contrast to unconjugated SEA, mediate the TCR interaction in a MHC class II-independent manner. The cytotoxic activity mediated by C215-SEA and C242-SEA conjugates was blocked by excess of C215 mAb and C242 mAb, respectively, showing that the specificity in the targeting of mAb-SEA conjugates is defined by the antigen reactivity of the mAb. These results demonstrate that bacterial superantigens may be successfully conjugated to mAb with preserved T cell-activating capacity. The circumvention of MHC class II binding of SEs by conjugation to mAb suggests that such conjugates may find general application as antitumor agents, taking advantage of the extreme T cell-activating potency of superantigens. PMID- 1924394 TI - Interleukin 1 expression is inducible by nerve growth factor in PC12 pheochromocytoma cells. AB - Expression of the cytokine interleukin 1 alpha (IL-1 alpha) was demonstrated in the rat PC12 pheochromocytoma cell line by (i) immunohistochemistry using rabbit polyclonal antisera raised against the recombinant murine IL-1 alpha, (ii) an ELISA, and (iii) a specific cell conversion bioassay based on the use of LBRM33 1A5 cells. IL-1 alpha mRNA was demonstrated in the PC12 cells, by PCR amplification. Constitutive expression of IL-1 alpha in PC12 cells was demonstrated in all experiments, although the cellular levels of IL-1 alpha-like immunoreactivity varied. The expression of IL-1 alpha, as studied at the mRNA level, was inducible by mouse nerve growth factor (7S NGF), and the gene product level was inducible in a dose- and time-dependent fashion by 7S NGF. The maximum induction corresponds to a 600% increase in IL-1 alpha-like immunoreactivity above the expression level found in noninduced cells and occurred after a 3-day incubation of the cells with NGF at 0.75 micrograms/ml of culture medium. The significance of the ability of NGF to induce IL-1 expression lies in the fact that IL-1 itself also acts as a growth factor that promotes glial proliferation and, even more importantly, IL-1 itself induces the expression of NGF at peripheral nerve injury [Lindholm, D., Heumann, R., Meyer, M. & Thoenen, H. (1987) Nature (London) 330, 658-659]. PMID- 1924395 TI - Critical role of a hydrogen bond in the interaction of phospholipase A2 with transition-state and substrate analogues. AB - The inhibition of phospholipase A2 by an amide substrate analogue, 1 hexadecylthio-2-hexadecanoyl-amino-1,2-dideoxy-sn-glycero-3-phos phocholine, and a phosphonate transition-state analogue, 1-hexadecylthio-1-deoxy-2 hexadecylphosphono-sn-glycero-3-ph osphocholine, is dramatically influenced by pH. However, these two inhibitors show opposite pH dependencies. The amide analogue acts more potently under basic conditions, whereas the phosphonate acts more potently under acidic conditions. In both cases, ligand binding is perturbed by protonation of an enzyme functional group with an apparent pKa of 6.1, which corresponds to that of a histidine residue. Thus, His-48, which has previously been implicated in catalysis, appears to be critically involved in the hydrogen bond interactions between the enzyme and these two inhibitors. The amide analogue binds most effectively to the enzyme when His-48 is deprotonated. Upon protonation of the histidine residue, the amide cannot form a critical hydrogen bond and loses its ability to interact effectively with the enzyme. In contrast, the phosphonate analogue binds much tighter to the protonated form of the enzyme than to the deprotonated form. The phosphonate analogue needs a bridging hydrogen between the oxygen on its phosphorus atom and the N delta 1 of His-48 to form a strong hydrogen bond. At optimal pH values for inhibitor binding, both the amide and the phosphonate analogues are potent competitive inhibitors of cobra (Naja naja naja) venom phospholipase A2. The IC50 for the amide was 4.4 x 10(-4) mol fraction and for the phosphonate was 1.6 x 10(-5) mol fraction. Under the experimental conditions used, this corresponds to a bulk concentration of 2 microM and 70 nM, respectively. PMID- 1924396 TI - Propeptide of carboxypeptidase Y provides a chaperone-like function as well as inhibition of the enzymatic activity. AB - The zymogen of the vacuolar carboxypeptidase Y from Saccharomyces cerevisiae was purified and characterized with respect to activation as well as refolding in vitro. The purified procarboxypeptidase Y has no detectable activity but can be efficiently activated by proteinase K from Tritirachium album. We used this method of activation as a tool for the investigation of refolding procarboxypeptidase Y in vitro. The proenzyme, denatured in 6 M guanidinium chloride, is renatured efficiently after dilution of the denaturant, whereas the mature enzyme regains little activity in the same procedure. Changes in intrinsic fluorescence reveal the mature enzyme to be considerably more stable than the proenzyme toward denaturation with guanidinium chloride. This suggests that the propeptide induces a metastable structure important for overcoming energy barriers that might otherwise obstruct a productive folding pathway. The relatively large number of charged amino acid residues and a high theoretical potential for alpha-helix formation in the carboxypeptidase Y propeptide suggest a structural similarity to a number of other propeptides and heat shock proteins. PMID- 1924397 TI - The phenotype of lymphoid cells and thymic epithelium correlates with development of autoimmune insulitis in NOD in equilibrium with C57BL/6 allophenic chimeras. AB - The mechanisms contributing to the development of autoimmune insulin-dependent diabetes mellitus have been analyzed in allophenic mouse chimeras of the NOD in equilibrium with C57BL/6 strain combination (where NOD is nonobese diabetic). Occurrence of lymphoid cell infiltration (insulitis) in pancreatic islets was observed in the majority of such chimeras. The development of insulitis was found to correlate with major histocompatibility complex chimerism in lymphoid cells and in thymus cortical regions. Chimeras with more than 50% of C57BL/6 lymphoid cells rarely developed insulitis. Our data suggest that the correlation with the thymic cortical region is absolute. Thus, all individuals displaying NOD or NOD/C57BL/6 thymic cortical regions developed insulitis, whereas we have not observed insulitis in chimeras with only C57BL/6 thymic cortical regions. Thus the positive selection of T cells appears to play a crucial role in the development of insulin-dependent diabetes mellitus. PMID- 1924398 TI - Models of human metastatic colon cancer in nude mice orthotopically constructed by using histologically intact patient specimens. AB - There is an important need for clinically relevant animal models for human cancers. Toward this goal, histologically intact human colon-cancer specimens derived surgically from patients were implanted orthotopically to the colon or cecum of nude mice. We have observed extensive orthotopic growth in 13 of 20 cases of implanted patient colon tumors. These showed various growth patterns with subsequent regional, lymph-node, and liver metastasis, as well as general abdominal carcinomatosis. Thus, models for human colon cancer have been developed that show (i) local growth, (ii) abdominal metastasis, (iii) general abdominal carcinomatosis with extensive peritoneal seeding, (iv) lymph-node metastasis, (v) liver metastasis, and (vi) colonic obstruction. These models permit the passage of the tumors to form large cohorts. They will facilitate research into the biology of colon cancer metastatic capability and the development of new drugs active against metastatic cancer. These models may also predict the clinical course and the in vivo response to drugs of the cancer of individual patients. PMID- 1924399 TI - Differential flexibilities in three branches of an N-linked triantennary glycopeptide. AB - The solution conformation behavior of complex oligosaccharides was studied by resonance energy transfer, as measured by the time-resolved fluorescence method, to determine the conformational heterogeneity of a triantennary glycopeptide at various temperatures. Groups that acted as a fluorescence donor (naphthyl-2 acetyl, Nap) or acceptor (dansylethylenediamine, Dan) were selectively attached to the N terminus of the peptide and a Gal residue [either 6' (shown below), 6, or 8] of the oligosaccharide, respectively. [formula: see text] Time-resolved fluorescence energy-transfer measurements revealed two populations of conformers when Dan was attached to either Gal-6' or Gal-6. One conformer contained the antenna folded back toward the core region, and a second was in an extended conformation. The two conformations differed in donor-acceptor distance by about 10 A. Systematically increasing the temperature from 0 degrees C to 40 degrees C increased the ratio of extended to folded forms 2-fold for the Gal-6 isomer and 4 fold for the Gal-6' isomer, whereas the Gal-8 isomer showed only a single distance population throughout this temperature range. From these data, delta H and delta S for the reversible conformational change were calculated to be 3.1 kcal/mol and 10.8 cal/(mol.K) for the Gal-6 isomer and 7.1 kcal/mol and 25.8 cal/(mol.K) for the Gal-6' isomer. In addition to the structural microheterogeneity commonly associated with glycoproteins, the differential flexibilities of the different branches in the oligosaccharides contribute conformational heterogeneity and should be considered in conformational analysis. The data are discussed in terms of the most probable linkages that contribute to the observed flexibility of the individual triantennary branches, and the biological significance of flexible linkages in complex carbohydrates is considered. PMID- 1924401 TI - Endogenous carcinogenesis: the role of tumor promotion. PMID- 1924400 TI - Hydrophobic ion transfer between membranes of adjacent hepatocytes: a possible probe of tight junction structure. AB - The topology of the tight junction is probed by introducing dipicrylamine (dpa-), a lipid-soluble anion, into the membranes of hepatocyte pairs in culture. Once partitioned into the membrane, dpa- ions are free to move in the hydrophobic core of the membrane, where their mobile charges greatly increase membrane capacitance. If tight junctions are lines of membrane fusion, dpa- will cross the tight junction without traversing a polar headgroup layer. Furthermore, the electric potential across the tight junction will be equal to the difference in membrane potentials of the two cells. dpa- can therefore be expected to move electrophoretically from cell membrane to cell membrane across the junction in response to an intercellular voltage difference. Experiments performed under double whole-cell clamp show that this transfer occurs as follows: First, dpa- causes an intercellular current unrelated to gap junctions to flow in response to an intercellular voltage difference. Second, this electrophoretic removal or addition of dpa- from a cell's membrane through the tight junction must reduce or increase its dpa- content and thus its capacitance. Experiments confirm this prediction: We detect rapid, symmetric, and reversible changes in membrane capacitance in response to changes in the membrane potential of the neighboring cell. Finally, we find that hepatocyte membranes contain a negatively charged endogenous molecule that contain a negatively charged endogenous molecule that can move from cell to cell like dpa- under the influence of an intercellular potential difference. We conclude that membrane fusion occurs at tight junctions and that this hydrophobic intercellular pathway can play a role in intercellular communication. PMID- 1924402 TI - The role oc endogenous factors in tumor promotion. SEBM symposium. Atlanta, Georgia, April 23, 1991. PMID- 1924403 TI - Sex hormones and tumor promotion in liver. AB - Epidemiological and experimental data strongly support a causal relationship between exposure to excessive levels of estrogens and the development of cancer in various tissues. In this paper, we have presented background information that shows a correlation between the prolonged use of oral contraceptives and the development of liver cancer. The clinical data supported the hypothesis that the estrogenic components of oral contraceptives were promoters of hepatocarcinogenesis, and the experimental evidence in support of this hypothesis and bearing on the mechanisms involved are also reviewed. The effects of estrogens on liver neoplasia and growth are: (i) synthetic steroidal estrogens are potent promoters of hepatocarcinogenesis in female rats; (ii) these estrogens stimulate liver growth at doses that are not hepatotoxic; (iii) the mechanisms by which the estrogens stimulate liver growth are indirect and include the enhancement of a serum/plasma growth factor, co-mitogenic effects which result in enhanced responsiveness of cultured hepatocytes to epidermal growth factor and decreased sensitivity of hepatocytes to growth inhibition by transforming growth factor-beta; (iv) the co-mitogenic effects of synthetic estrogens extend to endogenous estrogens and natural product estrogens; and (v) the co-mitogenic effects of estrogens for epidermal growth factor are associated with increased epidermal growth factor receptor protein levels caused by an increase in the half life of the receptor protein. The synthetic estrogens also have weak "complete" carcinogenic activity in rat liver and strong complete carcinogenic activity in Syrian hamster kidney and Armenian hamster liver. Evidence from the literature is presented in support of a hypothesis that this process may involve indirect genotoxicity mediated through redox cycling and the formation of hydroxylated DNA bases. This process, together with the potent promoting activity of these estrogenic chemicals, may account for their complete carcinogenicity. PMID- 1924404 TI - The role of cell proliferation in multistage carcinogenesis. PMID- 1924405 TI - Alterations in intercellular communication during the stage of promotion. AB - The promotion stage is a crucial step in the process of carcinogenesis. During this stage, the initiated cell population is clonally expanded to morphologically discriminable forms. Exogenous or endogenous agents that influence this clonal expansion have tumor-promoting activity. Inhibition of gap junctional intercellular communication is one of a number of cellular changes seen in cells after exposure to promoting agents. GJIC can be inhibited through either modification of intracellular control mechanism or through transcriptional or translational down-expression of the gap junction protein. Through either mechanism, the net effect is a decrease in GJIC by tumor promoters. This decrease in GJIC, while occurring in normal cells and preneoplastic cells alike, appears to be more efficacious in the preneoplastic cells, and appears to prevent GJIC between the preneoplastic cells and the normal surrounding hepatocytes. This isolation of the preneoplastic cells by hepatic tumor promoters from the normal surrounding hepatocytes may separate the preneoplastic cells from growth regulatory control of the normal liver, thus allowing the preneoplastic cells to clonally expand by cell proliferation. Whether the disruption of GJIC and down regulation of gap junction protein expression seen in hepatic foci by exposure to tumor promoters are causes or effects of the resulting cell proliferation remains to be determined. Certainly, the modification of GJIC and the expression of the gap junction protein by tumor promoters are important cellular changes that produce a phenotypically altered population of hepatocytes. PMID- 1924406 TI - Basic fibroblast growth factor-like substance in nuclei of male germ cells undergoing meiosis. AB - The presence of a basic fibroblast growth factor-like immunoreactive substance was demonstrated in the nuclei of germ cells at stages from spermatocyte to spermatid in adult rat testis by using immunohistochemistry with an antibody raised against a synthetic peptide corresponding to residues 1-10 of bovine basic fibroblast growth factor [1-146]. The fluorescence was very weak in the nuclei and cytoplasm of spermatogonia, Sertoli cells, and most of the interstitial compartments, except for capillary endothelial cells. This is the first study to demonstrate the presence of basic fibroblast growth factor-like immunoreactive material in the nuclei of haploid cells in vivo. PMID- 1924407 TI - Responses of the exocrine pancreatic secretion to spontaneous feeding in rats with bile-pancreatic juice diversion. AB - The regulatory response of the exocrine pancreas was examined in rats under unanesthetized and unrestrained conditions. The previous study demonstrated that the pancreatic protease secretion increased 2-fold after spontaneous feeding of a low protein diet in chronically bile-pancreatic cannulated rats (normal rats) whose bile-pancreatic juice (BPJ) was returned to the duodenum. In the present study, we observed the response of the exocrine pancreatic secretion to spontaneous feeding of a low protein diet in rats with chronic diversion of BPJ from the proximal small intestine for 6 days (bypass rat) whose diverted BPJ was returned to the upper ileum. During BPJ diversion, the dry weight and the protein content of the pancreas were increased 2-fold, compared with normal rats. Also, the levels of trypsinogen and chymotrypsinogen in the pancreas were increased several times, but amylase was decreased. The basal secretion of enzymes after a 24-hr fast was enhanced in bypass rats in proportion to the pancreatic enzyme contents. After spontaneous feeding of 8% casein fat-free diet, the increases in the pancreatic secretion of bypass rats were much smaller than those of normal rats. In contrast, the increase of BPJ flow of bypass rats after feeding was greater than that of normal rats. These findings represent that the chronic diversion of BPJ exerts hypergrowth of pancreas and hypersecretion of proteases in the fasting state, and less sensitivity of pancreatic enzyme secretion to dietary feeding. PMID- 1924408 TI - Circulating hormone concentrations in hypothyroid rats with induced polycystic ovaries. AB - The induction of polycystic ovaries in hypothyroid rats by human chorionic gonadotropin (hCG) has been studied for many years. A complete understanding of this phenomenon requires information regarding the circulating levels of the hormones of the hypophyseal-gonadal axis. In this study, serum prolactin (PRL), luteinizing hormone (LH), estradiol, testosterone, and progesterone were measured by radioimmunoassay at intervals during the 40-day period in which large ovarian cysts were induced in hypothyroid rats by daily injections of hCG. After 20 injections, ovaries increased in weight 10-fold, and well-developed ovarian cysts were present, accompanied by lutein tissue; cyst development continued for the subsequent 20 days of hCG. Both PRL and LH rose during the first 5 days of treatment and were maintained at high levels from day 20 on. The pattern of change of gonadal steroids showed greater increases with hCG in hypothyroid than in euthyroid rats. Levels of estradiol in hypothyroid, hCG-injected rats increased in parallel to ovarian hypertrophy, whereas progesterone was high in initial stages and then declined. Testosterone increased in both euthyroid and hypothyroid animals, with no clear pattern coincident with cyst formation. The data suggest that the formation of polycystic ovaries in the hypothyroid rat is associated with high levels of PRL and LH followed by elevations of estradiol, which may serve to maintain continuous PRL, as well as LH, stimulation of the ovary. PMID- 1924409 TI - Phosphate depletion reduces potassium-induced insulin secretion. AB - Potassium-induced insulin secretion is impaired in rats with chronic renal failure and a sustained rise in cytosolic calcium ([Ca2+]i). It has been found that the calcium signal (delta[Ca2+]i) and the delta [Ca2+]i/basal [Ca2+]i in these animals in response to potassium are smaller than those in normal rats and that these defects may underlie, at least in part, the reduced potassium-induced insulin secretion, since the latter depends on an appropriate rise in [Ca2+]i. Since phosphate depletion (PD) is another model associated with a rise in the basal level of [Ca2+]i of pancreatic islets, it provides another metabolic setting for investigating the interaction between high [Ca2+]i of islets and their response to potassium. We examined the potassium-induced insulin secretion, the potassium-induced calcium signal, and the delta [Ca2+]i/basal [Ca2+]i in islets of PD rats with and without elevated [Ca2+]i. The levels of the basal [Ca2+]i in the islets of PD rats were significantly (P less than 0.01) higher than those in pair-weighed (PW) animals and those in PD and PW rats treated with verapamil, which has been shown to prevent the rise in [Ca2+]i in islets of PD rats. Both initial and total insulin secretion, the calcium signal, and the delta [Ca2+]i/basal [Ca2+]i in the islets of PD rats were significantly (P less than 0.01) smaller than those in the other three groups of animals. There were no significant differences in basal levels of [Ca2+]i and in calcium signal, delta [Ca2+]i/basal [Ca2+]i, and insulin secretion among PW rats, verapamil-treated PD rats, and verapamil-treated PW rats. The results are consistent with the notion that elevated resting levels of [Ca2+]i interfere with the magnitude of the calcium signal and the ratio of calcium signal to basal [Ca2+]i, and these derangements, at least in part, underlie the impaired potassium-induced insulin secretion in PD. PMID- 1924410 TI - Relationship of cardiac hemodynamic and biochemical adaptations to mortality during long-term aortic constriction. AB - To determine the biochemical and hemodynamic responses to aortic ligation, and to assess the survival rate after the induction of hypertension, 90 normotensive rats were subjected to surgical constriction of the abdominal aorta. Mortality, left ventricular hemodynamics, myocardial biochemical assays, and plasma renin assays were determined 1 week, 1 month, 3 months, or 1 year later. Mortality was greatest between 1 week and 3 months after aortic ligation, during which plasma renin activity was significantly elevated. The rate of left ventricular pressure rise, contractile index, and myocardial alpha-adrenoceptor number were increased at 1 month, but were comparatively depressed at 3 months after the operation, suggesting that the heart was in failure at this time. At 1 year after ligation, hemodynamic and biochemical parameters continued toward normalization. Our data suggest that, in this rodent model, cardiac pump failure occurs through a combination of time-dependent, pressure-induced mechanical adaptations and myocardial biochemical changes that involve both the renin-angiotensin and sympathetic nervous systems. The observed relationship between mortality, myocardial hemodynamics, and biochemical parameters may be used for additional basic research investigations concerning the early periods of cardiac failure. PMID- 1924411 TI - Effect of certain growth factors on proliferation in serum-free collagen gel culture of vaginal epithelial cells from prepuberal mice exposed neonatally to diethylstilbestrol. AB - Neonatal treatment with diethylstilbestrol (DES) induces ovary-independent vaginal epithelial changes in mice. The response of vaginal epithelial cells from intact prepuberal BALB/cCrgl mice treated neonatally with 2 micrograms of DES for 5 days to growth-stimulatory and -inhibitory factors was studied using a serum free collagen gel culture system that sustains the growth of normal vaginal epithelial cells. Cells from control and DES-exposed mice at 21 days of age showed about a 5-fold increase in number during 10 days in a serum-free medium supplemented with transferrin, bovine serum albumin fraction V, insulin, and epidermal growth factor. Epidermal growth factor and insulin stimulated dose related proliferation of vaginal epithelial cells from both control and DES exposed mice; however, cells from DES-exposed mice showed a reduced growth response to epidermal growth factor and an increased growth response to insulin, compared with control cells. Insulin-like growth factor I (1-100 ng/ml) tested in the absence of insulin failed to stimulate cell growth. Transforming growth factor-beta (0.05-5 ng/ml) consistently inhibited cell growth in a dose-dependent manner. PMID- 1924412 TI - [Courses of specialization in Italy and complementary nursing education in the recommendation of the Council of Europe (R.5/83)]. PMID- 1924413 TI - [The project of complementary nursing education in critical areas]. PMID- 1924414 TI - [Complementary nursing education in the area of psychiatry and mental health]. PMID- 1924415 TI - [Complementary nursing education in the public health area]. PMID- 1924416 TI - [Complementary nursing education for coordinating nursing care]. PMID- 1924417 TI - [What are the prospects for complementary nursing education from the viewpoint of a project of university education for the nurse?]. PMID- 1924418 TI - [The experience of a "new" activity open to nurses for quality care]. AB - Nursing experience with Molnlycke, a multi-national company that is a leader in the field of products for incontinence. The company's policy of Total Quality is based on two main objectives: to offer products which guarantee maximum protection for the user (improved quality of life, prevention of infections caused by the catheter, decubital folds, irritation, etc.) and to provide a highly-qualified specialist service that is constantly available to our clients. The nursing personnel gather the essential data from within the various organizations (homes for senior citizens, local health authority units, social welfare residences, domestic social services), providing instructions for the correct utilization of the products and information relative to costs and benefits. This service provides advice, assistance and information; its purpose is to contribute to the continuing improvement of the products and services by means of systematic control and monitoring of their quality (Quality Assurance). PMID- 1924419 TI - Endotoxins and mediators--an introduction. PMID- 1924420 TI - Endotoxin-induced neutrophil activation--the role of complement revisited. PMID- 1924421 TI - Gram-negative bacterial sepsis in hospitals in the United States--natural history in the 1980s. PMID- 1924422 TI - Sources of endotoxin in the posttraumatic setting. PMID- 1924423 TI - Immunotherapy of gram-negative septicemia. PMID- 1924424 TI - Anti-lipopolysaccharide and anti-tumor necrosis factor/cachectin antibodies for the treatment of gram-negative bacteremia and septic shock. AB - Endotoxin is composed of lipid A, the toxic moiety, of the core region, a conserved structure among Gram-negative bacteria, and of the O-side chains, a highly variable part responsible for the antigenic specificity. The concept of cross-protection afforded by antiserum raised against the core region of endotoxin is supported by the following data: experimentally antiserum protected against infections caused by a wide range of Gram-negative bacteria or endotoxins; in patients with Gram-negative bacteremia, survival was associated with high levels of anti-core antibodies, and mortality was reduced by the prophylactic or therapeutic use of immune serum or plasma. However, the proof that protection is afforded by cross-protective anti-core antibodies is still lacking. Furthermore, many experimental studies and clinical studies trials have shown controversial results. Ongoing experimental studies and recently completed clinical trials, using either polyclonal or monoclonal anti-core antibodies should help clarify the issues both of the clinical efficacy and of the mechanism of protection. Tumor necrosis factor/cachectin has been unequivocally shown, both in experimental animal models and in humans to be a pivotal mediator of the clinical and humoral manifestations of shock induced by endotoxin or by whole Gram-negative bacteria. In humans, TNF was been transiently detected in the blood of volunteers challenged with endotoxin, in a small proportion of patients with Gram-negative sepsis, but in the vast majority of patients with established septic shock. However, in patients the magnitude and the evolution of the blood concentration of TNF differed from that observed in animal models or in human volunteers after an acute challenge with either Gram-negative bacteria or endotoxin, probably reflecting differences in infectious stimuli. In children with meningococemia and in adults with Gram-negative septic shock, TNF was associated with the patient's outcome. Anti-TNF monoclonal antibodies are presently undergoing clinical investigation in patients with septic shock. However, one should keep in mind that TNF serves both beneficial and detrimental functions depending upon its concentration in body fluids. PMID- 1924425 TI - Therapy of gram-negative sepsis in man with anti-endotoxin antibodies: a review. PMID- 1924426 TI - Randomized, double-blind phase II study of anti-endotoxin antibody (E5) as adjuvant therapy in humans with serious gram-negative infections. AB - Xomen-E5 (E5) is a murine monoclonal IgM antibody (MAb) that binds to the lipid A epitope of endotoxin. The MAb was developed by immunization against the J5 mutant of Escherichia coli. Prior studies in humans have shown safety and T1/2 of 18.4 hours. In this double blind study patients suspected to have life threatening gram-negative infections were randomized to receive 2 doses, 24 hours apart, of placebo (P), 2.5 mg/kg E5, or 7.5 mg/kg E5. Overall 23 patients had a documented serious gram-negative infection and received at least one dose of study drug. Mortality 3 days after last infusion was 2 of 9 for P, 0 of 9 for 2.5 mg/kg, and 0 of 5 for 7.5 mg/kg. By 21 days after therapy one E5 treated patient had died. Wheezes occurred in one E5 treated patient. Eight of 15 E5 patients treated had IgG anti-murine antibodies by 3 weeks after therapy. These data suggest the need to pursue studies designed to verify that E5 reduced mortality and morbidity in seriously ill patients with gram-negative infections. PMID- 1924427 TI - Antibodies to tumour necrosis factor in the treatment of severe sepsis: rationale and early clinical experience. PMID- 1924428 TI - Interleukin-1 as a therapeutic agent in serious infections? PMID- 1924429 TI - Effects of pentoxifylline in endotoxinemia in human volunteers. AB - The following effects of pentoxifylline in endotoxinemia in man could be demonstrated: 1. Il-6 release and Il-6 mediated effects such as clinical responses and leukocytosis are not inhibited by POF treatment. 2. TNF-alpha release is suppressed which might be the most important result, because TNF seems to play the major role in the pathophysiological events of endotoxinemia. Furthermore, pentoxifylline is able to counteract the initial leukocytopenia caused by sticking of leukocytes in the microcirculation. 3. De-novo-synthesis of cytokines by monocytes ex vivo is totally abolished. This may possibly reflect the in vivo situation. In conclusion, beneficial effects of pentoxifylline in respiratory distress syndrome, multi-organ failure and septic shock are suggested. Furthermore, our data indicate that endotoxin-induced formation of Il 6 and TNF-alpha are regulated independently in vivo. PMID- 1924430 TI - Severe human septic shock involves more than tumor necrosis factor. PMID- 1924431 TI - Comparison of the early dynamics of coagulation activation after injection of endotoxin and tumor necrosis factor in healthy humans. PMID- 1924432 TI - Differential induction of interleukin-6 production by monocytes, endothelial cells and smooth muscle cells. AB - Studying the production of IL-6 by monocytes, endothelial cells and smooth muscle cells we observed that cytokine inducers like IL-1, TNF alpha, LPS, SAC and PMA could be divided roughly into two categories. One, that consisted of LPS and SAC, which had a potent IL-6 inducing effect on monocytes and minor or no effect on endothelial- and smooth muscle cells. The other category, consisting of IL-1, TNF alpha and PMA, induced IL-6 production in endothelial- and smooth muscle cells and of which IL-1 also induced IL-6 in monocytes. Only IL-1 induced IL-6 production in monocytes as well as in endothelial cells and smooth muscle cells. Besides IL-6, also IL-1 and TNF alpha were produced by monocytes however with different kinetics. None of the stimuli had any inhibitory effect on IL-6 production with the exception of PMA. Whereas PMA induced IL-6 production in endothelial cells and it potentiated the induction of IL-6 by IL-1 in these cells, it inhibited LPS-stimulated IL-6 production in monocytes. In line with the effects of PMA, staurosporin induced IL-6 production in monocytes and it inhibited IL-1 driven IL-6 production by endothelial cells. PMID- 1924433 TI - The role of lipoxygenases in endotoxin-induced cytokine production. AB - The LPS induced synthesis of tumor necrosis factor in macrophage cultures, as determined in a fibroblast cytolysis assay was found to be effectively blocked by inhibitors of lipoxygenases. Likewise, the presence of tumor necrosis factor in serum of D-galactosamine sensitized mice after challenge with endotoxin was suppressed by the lipoxygenase inhibitors. From LPS-treated macrophages 13 hydroxylinoleic acid, a lipoxygenase product was isolated, which is significantly increased after LPS treatment of the cells, covalently bound to cellular constituents and was found to counterbalance the suppression of TNF-synthesis by a lipoxygenase inhibitor when added to macrophages exogenously. PMID- 1924434 TI - Markers of endotoxin related leukocyte activation and injury mechanisms. PMID- 1924436 TI - Urological oncology: reconstructive surgery, organ conservation, and restoration of function. Proceedings of the sixth course in urological oncology. Sicily, Italy, March 25-31, 1990. PMID- 1924437 TI - Tumor enucleation of renal cell carcinoma: operative technique, DNA cytometry results, complications. PMID- 1924438 TI - Bladder substitution with the Stanford Pouch. PMID- 1924435 TI - The role of cachectin/TNF and other cytokines in sepsis. AB - A traditional view has been that bacterial products, such as endotoxins from gram negative bacteria, have a direct deleterious effect on the host, resulting in fever, hypermetabolism, anorexia, and tissue damage. In recent years, however, it has been shown that endogenous products of the host, secreted by macrophages and other cellular elements of the immune system, act as mediators in activating the metabolic and other physiological changes characteristic of the sepsis syndrome. We will review in depth various aspects of the major, central mediator, i.e., tissue necrosis factor (TNF)/cachectin, and also briefly discuss the interleukins IL-6 and IL-1. PMID- 1924439 TI - The Maryland Pouch reconstruction--technical improvements and update. PMID- 1924441 TI - Organ conservation in bladder cancer. PMID- 1924440 TI - Organ conservation in deeply invasive bladder cancer. PMID- 1924442 TI - Organ conservation and reconstruction in advanced bladder cancer. PMID- 1924443 TI - Organ reconstruction and conservation in bladder cancer. PMID- 1924444 TI - Innovative technique for urethrectomy. Prepubic technique and results in 41 patients. PMID- 1924445 TI - Reconstruction of the urinary tract after radiation fistulae. PMID- 1924446 TI - Percutaneous operative gastrostomy in uro-oncological surgery. Operative technique and results in 53 patients. PMID- 1924447 TI - Operative factors & tumor membrane antigen changes in escape from immune surveillance of bladder cancer. AB - 1. Survival of skin allografts in mice is increased in proportion to the duration of anaesthesia to a degree that is equivalent to that achievable with a major immunosuppressive agent such as azothiaprine or antilymphocyte serum. 2. Immune cytochemical studies have demonstrated that bladder tumors which metastases express beta HCG and show variable degrees of loss of HLA class I antigens- features which mimic the behaviour of human trophoblast in protecting the foetus from maternal rejection. It is concluded that there may be a case for using such prognostic factors to define a sub group of patients in whom reconstruction of the bladder following cystectomy should be deferred until the patient has survived without metastases for a prolonged period. PMID- 1924449 TI - Intravesical sequential combination of epirubicin and interferon alpha-2b in patients affected by superficial transitional cell carcinoma of the bladder. Results of a pilot study at Palermo University and proposal of a basic research. PMID- 1924448 TI - Urinary evaluation of tumor-associated antigens in urothelial bladder tumors. PMID- 1924450 TI - Hemangioma of the kidney: the role of preoperative imaging for kidney survival. PMID- 1924451 TI - Organ preservation in superficial bladder cancer. PMID- 1924452 TI - Are organ preservation and maintenance of sexual function compatible with optimal management of prostate cancer? Part 2--Advanced cancer. PMID- 1924453 TI - Interferon and hormone-sensitivity of prostatic cancer cells. PMID- 1924454 TI - Lessons from in vitro studies on human and canine prostate epithelial cell lines. PMID- 1924455 TI - Can pathology predict response role of classic methods and modern techniques. PMID- 1924456 TI - The prostate in eunuchs. AB - In 1960, there were 26 eunuchs from the palace of the Qing Dynasty still living in Beijing. The authors took that unique opportunity of carrying out a general physical examination, including palpation of the prostate, for every one of them. Their average age then was 72 years (59-83 years). They became eunuchs at the age of 10-26 years. The prostate was impalpable in 26 (81%) and 1-2 cm in width rectally in five, with a flat surface. At the time of the examination they had been eunuchs on the average for 54 years (41-65 years). This is probably the largest series of human beings followed for such a long period of time to confirm that testicular hormone is essential for the development and preservation of the prostate. The type of operation, the traditional way of carrying out the operation and the usual complications are presented. PMID- 1924457 TI - Renal-sparing conservative treatment of the upper urinary tract tumors. PMID- 1924458 TI - Organ and function preservation after X-irradiation for prostatic cancer. PMID- 1924459 TI - Transurethral resection and laser irradiation in low stage prostatic carcinoma. PMID- 1924460 TI - External beam irradiation combined with the use of 192-iridium implants and radiofrequency-induced hyperthermia in the treatment of prostatic carcinoma. PMID- 1924461 TI - Iridium-192 implants in patients with large stage C prostate cancer. PMID- 1924462 TI - Transrectal ultrasound-guided interstitial radiation therapy for localized prostate cancer. PMID- 1924463 TI - Surgical margins at radical prostatectomy. PMID- 1924464 TI - Why not neo-adjuvant therapy for prostatic carcinoma? PMID- 1924465 TI - Preserving the prostate. PMID- 1924466 TI - The present role of estramustine phosphate in advanced prostate cancer. AB - With estramustine phosphate the clinician has the possibility to ensure complete hormonal as well as cytotoxic control of advanced prostate cancer with a single drug. EMP is considered as a first choice for treatment of hormone refractory prostate cancer. It is at least as effective as conventional chemotherapy, yet less aggressive with regard to its toxicity profile. EMP is particularly useful in patients with limited bone marrow reserve, e.g. in case of prior or associated radiotherapy. As to the use of EMP in primary treatment, more information is required before we can define with certainty subgroups of patients who would benefit more from an early course of EMP than from other hormonal therapy. The existing data point in the direction of poorly differentiated tumors, patients with bone pain and poor prognosis. EMP treatment is associated with an increased risk of cardiovascular morbidity. This should be avoided as much as possible by proper selection of patients or by prophylaxis. Gastro-intestinal side effects, such as nausea, diarrhea and anorexia are dose-dependent. These adverse events tend to interfere with compliance at dosages over 560 mg/day. Dosage modifications or an anti-emetic may help. The intravenous administration of EMP offers the possibility for high loading doses at a substantially reduced risk for cardiovascular and gastrointestinal side effects. PMID- 1924467 TI - Prostate cancer: should potency be preserved by deferring hormonal treatment in patients with asymptomatic metastatic disease? PMID- 1924468 TI - Postoperative erectile dysfunction; evaluation and treatment with intracavernous vasoactive injections. PMID- 1924469 TI - Peyronie's disease: pathophysiology. PMID- 1924470 TI - Surgical treatment of patients with Peyronie's disease. PMID- 1924471 TI - Penis construction. PMID- 1924472 TI - Reconstruction of the ureter. PMID- 1924473 TI - Male to female gender reassignment--some social and technical problems. PMID- 1924474 TI - Successful management of malignant melanoma of male urethra with local excision and adjuvant radiochemotherapy. PMID- 1924475 TI - Tumor collagenase stimulating factor (TCSF) and tumor autocrine motility factor (TAMF) in bladder cancer. PMID- 1924476 TI - Radical retroperitoneal node dissection after chemotherapy for testicular tumours. PMID- 1924477 TI - Nerve sparing surgery in testis cancer. PMID- 1924478 TI - Results of laser therapy for carcinoma of the penis: organ preservation. PMID- 1924479 TI - Ureteral substitution by non-refluxing ileal loop. PMID- 1924480 TI - Continent urinary diversion by an ileal bladder substitute. PMID- 1924481 TI - The Studer-Zingg ileal-neobladder: the "ideal" bladder substitute? PMID- 1924482 TI - Preservation and restoration of function--continence of the ileal neobladder. PMID- 1924483 TI - Continence mechanisms following continent urinary diversion and orthotopic bladder replacement. AB - It is obvious that significant advances have been made in reconstruction of the lower urinary tract following radical pelvic surgery. In contrast to the standard ileal loop, patients no have an option to void per urethra, have social continence and avoid self-intermittent catheterization in the presence of an abdominal stoma. Further refinements in construction of the continence mechanism will undoubtedly occur in the future. PMID- 1924484 TI - Conservative surgery of kidney tumors. PMID- 1924485 TI - Restoration of voiding function. PMID- 1924486 TI - The Studer ileal neo-bladder: anatomical and functional characteristics. PMID- 1924487 TI - [The permeability barrier of the skin]. PMID- 1924488 TI - [Gastric juice resistance--does it really exist? Possibilities and limitations of gastric juice-resistant drug forms]. PMID- 1924489 TI - [Expanding polymers for hydrogel- and hydrocolloid-embedding for sustained release drug liberation]. PMID- 1924490 TI - Chronic DMI reduces thresholds for brain stimulation reward in the rat. AB - The authors sought a demonstration of the validity of brain stimulation reward (BSR) models of depression. It was predicted that chronic, but not acute antidepressant treatment would enhance BSR responding. Rats with medial forebrain bundle electrodes were separated into 4 groups that received either saline or desmethylimipramine at 5, 10, or 20 mg/kg daily. A rate-free, threshold measure that has not previously been employed in studies of BSR and antidepressants was used. BSR thresholds were monitored every 3rd day over a 9-day baseline period and an 18-day drug treatment period, and after 12 days of drug withdrawal. Groups did not differ from one another till the 15th and 18th day of drug treatment. The greatest effects were seen in the 10 and 20 mg groups. The 20 mg group returned to baseline after drug withdrawal, but the 10 mg group did not. The absolute size of the effect was considered to be small, leading the authors to speculate that antidepressants act on homeostatic mechanisms that stabilize BSR substrates, only indirectly enhancing transmission of the reward signal. PMID- 1924491 TI - Dopamine D2 receptor blocking effect of imipramine in the rat hippocampus. AB - The effect of dopamine receptor agonists on the spontaneous bioelectrical activity of CA1 layer neurons in the hippocampal slice preparation from the rat brain was studied. Two groups of rats were used: control and imipramine pretreated ones (twice a day, for two weeks, 10 mg/kg PO). Dopamine and the selective D2 receptor agonist quinpirole induced an excitatory reaction; a similar effect was evoked by amphetamine, an indirect dopamine agonist. The effects of the three compounds were diminished by sulpiride. Perfusion of control slices with imipramine decreased the excitatory effect of dopamine, amphetamine, and quinpirole. The effect of dopamine agonists was also inhibited 2 h after repeated pretreatment with imipramine. The excitatory effect of the dopamine agonist was enhanced 48 h after the last dose of imipramine, the latter effect was blocked by a 60-min perfusion of slices with imipramine or sulpiride in the experimental chamber. The obtained data show that acute imipramine induces blockade of dopamine D2 receptors in the hippocampus. This effect is probably responsible for development of supersensitivity of dopamine D2 mechanisms after prolonged treatment with imipramine in this brain region. PMID- 1924492 TI - D-2 agonists protect rodents against pilocarpine-induced convulsions by stimulating D-2 receptors in the striatum, but not in the substantia nigra. AB - This study employed the pilocarpine model of epilepsy to determine the relative systemic anticonvulsant potencies of five different D-2 agonists in the mouse, and to investigate the site of anticonvulsant action of LY 171555 in the rat's brain following intracerebral microinjection. Control mice pretreated with saline developed motor seizures when challenged with pilocarpine (400 mg/kg, 11/13 convulsed). D-2 agonists protected mice against pilocarpine-induced seizures in the rank order of potency PHNO greater than pergolide greater than greater than lisuride = LY 171555 much greater than RU 24213, with ED50 values ranging from 0.17 mg/kg for PHNO to greater than 4.5 mg/kg for RU 24213. The response to LY 171555 was abolished by the D-2 blocker metoclopramide (1.25 mg/kg), but not by the D-1 antagonist SCH 23390 (0.25 mg/kg). All D-2 agonists induced head-down sniffing and forward locomotion, consistent with central D-2 activation. LY 171555 (ED50 0.19 mg/kg), but not RU 24213 (ED50 greater than 4.5 mg/kg), was similarly efficacious in the rat. When injected into both hemispheres of the conscious rat via indwelling cannulae, intrastriatal saline failed to afford protection against the convulsant action of pilocarpine (600 mg/kg, 13/15 convulsed), whereas LY 171555 did (1 microgram, 1/12 convulsed). Intrastriatal RU 24213 (1 microgram per side) was without effect (7/10 convulsed). Similarly, no protection resulted when saline (15/16 convulsed) or LY 171555 (1 microgram, 17/23 convulsed) were delivered into both nigras. It is concluded that in this model of limbic seizures in the mouse and rat, D-2 agonists exert a powerful anticonvulsant effect which is mediated by D-2 receptors in the striatum, but not by D-2 receptors in the substantia nigra. PMID- 1924493 TI - An in vitro study on the hippocampal electrophysiological properties of enkephalinase inhibitors in rats. AB - The effects of two enkephalinase inhibitors were studied on the CA1 and dentate hippocampal extracellular field potentials (FPs). The enkephalinase inhibitors thiorphan and SCH 32615, at a concentration of 1-500 microM, failed to significantly affect CA1 and dentate FPs. Thiorphan and SCH 32615, at a concentration of 150 microM, were able to potentiate the enkephalin-induced epileptiform bursting, inducing an increase in the bursting duration and in the number of spikes per burst due to 3.5 microM DAEAM or 0.20 microM DAGO. The results suggest: 1) the potentiation of an electrophysiological opiate receptor mediated response by enkephalinase inhibitors; 2) the inability to show a direct effect on the basal CA1FP as a result of the inhibition of the endogenous enkephalinase. PMID- 1924494 TI - The pentylenetetrazole-cue antagonist actions of bretazenil (Ro 16-6028) as compared to midazolam. AB - In order to compare the potencies of bretazenil (Ro 16-6028) and midazolam (MDZ) to antagonize the pentylenetetrazole (PTZ) cue, rats were trained to discriminate between 15 mg/kg IP PTZ and saline (FR10, food reinforced). Additionally, other rats were trained to discriminate between 1.0 mg/kg IP MDZ and saline in order to investigate the degree of generalization of bretazenil to MDZ, and to test for the antagonizing effects of PTZ. Both bretazenil and MDZ were able to block the PTZ cue. Bretazenil was about 60 times more potent than MDZ in this respect. In tests for response generalization, bretazenil substituted for MDZ cue. Bretazenil did not show MDZ-antagonist actions. PTZ did block the MDZ cue and the generalization of bretazenil in the MDZ-trained animals. Assuming that the drug discriminative stimulus functions of PTZ are closely related to its anxiogenic effects, it was concluded that bretazenil may possess powerful anxiolytic properties. Bretazenil did not suppress the response rates which is consistent with previous studies reporting a lack of sedative and muscle-relaxant effects of bretazenil. PMID- 1924495 TI - Upper airway and diaphragmatic muscle activity following acute cocaine administration. AB - These studies examined activity of the diaphragm and a laryngeal dilator, the posterior cricoarytenoid, following 3 levels of intravenous and cerebral ventricular administration of cocaine. Both administration routes induced extremely high respiratory rates with enhanced tonic and phasic electromyographic activity, and affected patterning similarly in upper airway and diaphragmatic muscles. Both intravenous and intraventricular administration induced a rise in core and brain temperature related to the route of administration; however, the tachypnea was only loosely related to the hyperthermia. Intraventricular administration resulted in a more rapid onset of peak respiratory rates, and a faster decline than an intravenous route. Different dose levels elicited similar elevated respiratory rates, but higher intravenous doses also resulted in extensive hypertonicity with intermittent phasic movements. Tachypnea continued between these phasic efforts. The phasic events associated with high doses were accompanied by sustained inspiratory efforts; however, no evidence of obstructive apnea was found. These data suggest that cocaine can modify respiratory patterning by inducing a centrally mediated tachypnea and by eliciting sustained, intermittent inspiratory efforts. PMID- 1924496 TI - Luteinizing hormone releasing hormone-induced conditioned place-preference in male rats. AB - Conditioned place-preference induced by intraperitoneal injections of luteinizing hormone releasing hormone (LHRH) was studied in male rats. In Experiment 1, dose dependent effects (doses: 0, 0.2, 1 and 5 micrograms/kg) were observed in gonadectomized males provided with a subcutaneous silastic implant containing testosterone. Animals injected with 1 or 5 micrograms LHRH developed reliable preference for the LHRH-associated compartment of a two-compartment preference box. The 0 and 0.2 microgram doses were without effect. Experiment 2 further studied the place-preference effects induced by 5 micrograms LHRH, by varying the sex steroid baseline condition of the animals. A significant effect of LHRH on place-preference was found in gonadectomized males with a testosterone or estradiol implant and in gonadally intact males. Differences between these groups were not found. However, in gonadectomized males without steroid substitution, LHRH did not induce place-preference. These data indicate that rewarding properties related to LHRH treatment can be observed in male rats, provided that the males are additionally exposed to sufficient levels of circulating sex steroids. PMID- 1924497 TI - Conditioned tolerance to the heart rate effects of smoking. AB - This study extended our findings that behavioral tolerance to nicotine in animals can be influenced by conditioning to cardiovascular tolerance in humans. Subjects smoked one-half a cigarette during each of five trials. In the ten-minute intersmoking interval the contexts that preceded smoking were varied. Smokers in the Changing group attended to a different five-minute segment of a Sherlock Holmes radio mystery before each trial, while those in the Repeated group listened to the same segment of the tape. Presmoking heart rates were stable across the groups from trials 1 to 5. As predicted, heart rate for subjects who smoked in the same context showed tolerance to smoking from trials 1 to 5 (84.5 to 78 bpm), while subjects who smoked in in the same context showed tolerance to 83.9 bpm). COa levels increased equally for both groups over the five trials. The results of this study suggest tolerance to smoking can be influenced by learning. PMID- 1924498 TI - HPLC-purified human satietin does not produce conditioned taste aversion in rats. AB - Human satietin is thought to be an endogenous glycoprotein that can suppress food intake and body weight. However, it was also found to be aversive when rats infused intracerebroventricularly (ICV) with human satietin were subjected to a two-bottle taste aversion test. More recently, the human satietin previously thought homogenous was separated by HPLC into two Peaks, denoted as A and B. In the present study, male Sprague-Dawley rats were fitted with chronic third ventricle cannulas and presented with fluid for 1 h/day, while food was given ad lib. After training, the rats were ICV infused with either artificial cerebrospinal fluid, Peak A or Peak B of human satietin. Peak B significantly reduced short-term and 24-h food intake, whereas their fluid intake was nonsignificantly attenuated. Peak A had no affect on either food or fluid intake on the day it was administered. When the rats were given the two-bottle taste aversion test neither compound was found to be aversive. These data suggest that Peak B may contain satietin(s) which could be a candidate for an endogenous satiety agent. PMID- 1924499 TI - Desipramine enhances isolation-induced aggressive behavior in mice. AB - Effects of desipramine on aggressive behavior induced by long-term (6-7 weeks) isolation of mice were examined. Aggressive behavior was measured as duration of biting attack and/or wrestling during a 20-min observation period. Desipramine (5, 10 and 20 mg/kg, IP) and imipramine (10 and 20 mg/kg, IP) dose-dependently increased the duration of aggressive behavior in isolated mice, without inducing aggressive behavior in group-housed animals. Desipramine-induced increase in aggressive behavior was blocked by phentolamine (3 mg/kg, IP) and yohimbine (0.3 mg/kg, IP), but not prazosin (0.5 mg/kg, IP). Clonidine (0.001 mg/kg, IP), an alpha 2 agonist, significantly blocked desipramine-induced enhancement of aggressive behavior in isolated mice without affecting the basal aggression. These data suggest that long-term isolation may induce functional changes in the sensitivity of alpha 2 receptor in the noradrenergic system and that desipramine enhancement of aggressive behavior in isolated mice is modulated by drugs acting onto alpha 2 noradrenergic receptors. PMID- 1924500 TI - Effect of the 5-HT2 antagonist ketanserin on salt appetite in the rat. AB - The 5-HT2 antagonist ketanserin inhibited salt appetite induced by subchronic deoxycorticosterone acetate (DOCA) treatment, as well as salt appetite induced by sodium depletion (which is governed by the synergy of aldosterone and angiotensin in the brain). The effect of ketanserin was more evident following intraperitoneal than intracerebroventricular injection. On the other hand, ketanserin did not inhibit either salt intake induced by intracranial renin injection, or the need-free salt intake of the multidepleted female rat, which is not dependent on the renin-angiotensin-aldosterone system. These findings suggest that the antinatriorexic action of ketanserin is selective for the mineralcorticoid mechanisms controlling salt appetite. Ritanserin, too, a potent 5-HT2 antagonist showing a different receptor selectivity profile from that of ketanserin, suppressed DOCA-induced salt appetite, thus supporting the involvement of 5-HT receptors in the antinatriorexic action. DOCA treatment alters serotonin metabolism in the central nervous system and it has been proposed that changes in 5-HT metabolism may be important in the genesis of DOCA induced hypertension. The present results indicate that ketanserin inhibits DOCA induced salt appetite and suggest that serotoninergic mechanisms might be involved in the elicitation of mineralocorticoid-induced salt appetite. PMID- 1924501 TI - Effects of MDA on classical conditioning of the rabbit nictitating membrane response. AB - In Experiment 1, classical conditioning of the rabbit's nictitating membrane response (NMR) was accomplished by pairing tone and light conditioned stimuli (CSs) with a shock unconditioned stimulus (UCS). MDA impaired the acquisition of conditioned responses (CR) to a tone-CS, while significantly enhancing CR acquisition to a light-CS. Experiment 2, employing explicitly unpaired CS, UCS training, revealed no reliable effects of MDA upon nonassociative processes. Subsequent efforts determined if MDA's CR acquisition effects resulted from alterations in sensory processing of the CS, UCS, and/or UCR motor functioning. Specifically, it was determined that MDA: (a) increased the tone-CS intensity threshold for eliciting CRs (Experiment 3); (b) attenuated the tone-induced reflex modification of the unconditioned NMR (Experiment 4); and (c) enhanced UCR frequency at varying UCS intensities (Experiment 5). It was concluded that MDA's effect upon CR acquisition reflected the drug's effect upon CS and UCS/UCR processing and thereby altered the ability of these components of conditioning to enter into associative learning. PMID- 1924502 TI - Psychological stress-induced increases in noradrenaline release in rat brain regions are attenuated by diazepam, but not by morphine. AB - By measuring levels of noradrenaline (NA) and its major metabolite, 3-methoxy-4 hydroxyphenylethyleneglycol sulfate (MHPG-SO4) in the hypothalamus, amygdala and locus coeruleus region, we investigated the effects of diazepam 5.0 mg/kg, morphine 6.0 mg/kg, or naloxone at 5.0 or 10 mg/kg injected SC immediately before stress exposure, on increases in NA release caused by psychological stress. Psychological stress, wherein rats were exposed to emotional responses which were displayed by other electrically shocked rats, significantly increased MHPG-SO4 levels in the three brain regions examined and elevated plasma corticosterone levels. Both increases in brain MHPG-SO4 levels and elevations of plasma corticosterone levels induced by stress were attenuated significantly by diazepam but neither by morphine nor by naloxone. MHPG-SO4 levels in the hypothalamus and amygdala in the morphine-stress group were significantly higher than those in the saline-stress group. These findings suggest that psychological stress, in which an emotional factor is predominantly involved, causes increases in NA release in these brain regions examined and that these increases are attenuated only by diazepam, in contrast to the previous report, where increases in brain NA release caused by immobilization stress are attenuated not only by diazepam but also by morphine and are enhanced by naloxone. PMID- 1924503 TI - Effects of oxiracetam-nicotine combinations on active and passive avoidance learning in mice. AB - Tested alone, in CD-1 mice, the nootropic drug oxiracetam (50 mg/kg) improved learning in a multitrial active avoidance task (shuttle-box), but did not affect one-trial passive avoidance acquisition. Nicotine, which was ineffective at the dose of 0.25 mg/kg, improved both active and passive avoidance at the dose of 0.5 mg/kg; 1 mg/kg nicotine still exerted facilitating effects on passive avoidance, but slightly depressed shuttle-box performance. Combinations of oxiracetam and nicotine improved passive avoidance more than either drug given separately. In the active avoidance task, a combination of oxiracetam with the lower dose of nicotine exerted improving effects never observed with nicotine alone, even at higher doses. The nootropic drug also prevented the slight depressant action exerted by 1 mg/kg nicotine. Thus, contrary to what was previously supposed, at least in mice subjected to shuttle-box avoidance training, nicotinic activation does not appear as the main neurochemical mechanism involved in the action of oxiracetam. Perhaps, oxiracetam and nicotine activate different types of cholinergic mechanisms, but it cannot be excluded that other neurotransmitters, particularly catecholamines, may be involved in the avoidance facilitating effects produced by nicotine and by combinations of the two drugs. PMID- 1924504 TI - Intracerebroventricular cholecystokinin infusions block beta-endorphin-induced disruption of maternal behavior. AB - Recent work has shown that infusions of beta-endorphin, an endogenous opioid, into the ventricular system of lactating rats blocks normal maternal behavior. Other behavioral and biochemical studies have demonstrated that sulfated cholecystokinin-octapeptide (CCK-8) can have effects opposite those of opioids. The present study evaluated whether intracerebroventricular (ICV) administration of CCK-8 is able to antagonize the inhibitory effect of beta-endorphin on maternal behavior. The results of this study demonstrated that CCK-8 (14.5 nmol) prevented the beta-endorphin (1.45 nmol)-induced increase in latencies to retrieve the first pup, retrieve all pups, and to group and crouch over rat pups. In addition, reductions in the percentage of rats retrieving all pups and displaying full maternal behavior were prevented by CCK-8. These data suggest that CCK-8 can act as an opioid antagonist in neural systems that control maternal behavior. PMID- 1924505 TI - The effect of subchronic administration of vigabatrin on learning and memory in nonepileptic rats. AB - The present experiments investigated whether subchronic administration of vigabatrin, a GABA-mimetic drug, affects the performance of normal rats in the behavioural tasks assessing learning and memory. The effects of vigabatrin [50 200 mg/kg (IP)/day] administration on the acquisition and retention of water maze and passive avoidance task were studied. According to the results of three experiments, vigabatrin treatment did not markedly impair the acquisition or retention of water maze task. Furthermore, vigabatrin-treated rats were not inferior to saline-treated rats in reversal learning of water maze task. On the other hand, vigabatrin treatment slightly increased the speed of swimming in rats. The administration of vigabatrin did not affect the performance (training latency, number of training trials, testing latency) of rats in the passive avoidance task. According to these results, the effects of vigabatrin, a new antiepileptic drug, on the performance of nonepileptic rats were modest in behavioural tasks used to assess learning and memory. PMID- 1924506 TI - Paradoxical effects of exogenous norepinephrine on cold-induced thermogenesis in the rat. AB - The effect of norepinephrine (NE, 250 microgram/kg IP) on thermoregulatory behavior of rats in a cold environment was tested. Norepinephrine produced an increase in operant responding for heat reward but a decrease in core temperature. Since animals compensate behaviorally for alterations in autonomic thermoregulation, this suggested that NE might inhibit cold-induced thermogenesis, an effect contrary to the expected action of this agent. A second experiment showed that NE increased oxygen consumption when rats were tested at 25 degrees C as expected, but decreased oxygen consumption when tested at 5 degrees C. The beta-adrenoceptor antagonist propranolol decreased oxygen consumption both at 25 and at 5 degrees C as expected. These results suggest that the thermogenic effect of NE is highly dependent on ambient temperature. PMID- 1924507 TI - Effect of REM sleep deprivation on rat brain acetylcholinesterase. AB - Acetylcholinesterase activity was compared in control, rapid eye movement sleep deprived and recovered rat brain. The activity was estimated in the whole brain, cerebrum, brain stem and cerebellum. Flower pot technique was used for continuing deprivation for two, four and eight days. The results showed that the enzyme activity increased significantly in the deprived rat brain and it returned to control/normal level on recovery. The enzyme activity increased first in the brain stem, while the activity in the cerebellum showed no significant change. Control experiments suggest that the increase was primarily caused by the deprivation. The finding fits well with existing knowledge and would possibly help in explaining earlier observations. PMID- 1924508 TI - Oxytocin inhibits male sexual behavior in prairie voles. AB - Intracerebroventricular (ICV) injection of oxytocin (300 ng) produced an immediate cessation in sexual behavior in sexually active male prairie voles (Microtus ochrogaster). Other social behaviors including social contact, aggression, and autogrooming were not significantly affected by oxytocin, but males that received oxytocin ICV, versus injections that missed the ventricles, showed more sleep postures. Sexual behavior remained inhibited for at least 24 hours and was not activated in tests with a novel receptive female. Sexual and social behavior were not significantly altered in animals in which the oxytocin injection missed the ventricles or in saline-treated males. These findings are consistent with the hypothesis that oxytocin plays a role in sexual satiety. PMID- 1924509 TI - The effects of increased serotonergic and decreased cholinergic activities on spatial navigation performance in rats. AB - In the present set of experiments the effects of a serotonin (5-HT) reuptake blocker, alaproclate (alap) and of a muscarinic antagonist, scopolamine (scop) on place navigation (hidden platform) and cued navigation (visible platform) water maze tasks were investigated. In hidden platform experiments it was observed that scopolamine (0.8 mg/kg) impaired performance (increased escape distance). Alaproclate 7.5 mg/kg and 20 mg/kg, but not 2.5 mg/kg produced a significant impairment. The combination of the highest dose of alaproclate (20 mg/kg) and of scopolamine (0.8 mg/kg) produced a far greater place navigation deficit than scopolamine (0.8 mg/kg) alone. Pilocarpine (pilo) (6.0 mg/kg) reversed the impairment induced by scopolamine (0.8 mg/kg) alone, but the impairment induced by a combination of scopolamine (0.8 mg/kg) and alaproclate (20 mg/kg) was only partially reversed. In visible platform experiment the administration of scopolamine (0.8 mg/kg) did not impair performance, but alaproclate (20 mg/kg) impaired acquisition. Scopolamine (0.8 mg/kg) did not augment alaproclate-induced deficit in visible platform version of the task. In conclusion, we suggest that pharmacological modulation of serotonergic and cholinergic systems affects spatial navigation by modulating different mechanisms underlying different navigation strategies. PMID- 1924510 TI - Effects of ethanol on body temperature of rats at high ambient pressure. AB - Separately, ethanol and high ambient pressure cause hypothermia in laboratory animals. However, ethanol and high pressure have mutually antagonistic effects on several biological functions and the present experiments investigate their combined action on body temperature. Rats given saline, 1.5 g/kg ethanol or 3.5 g/kg ethanol were exposed to 1 bar air at 25-26 degrees C, 1 bar helium-oxygen at 30-31 degrees C, or 48 bar helium-oxygen at 33.5-34.5 degrees C. Ambient, colonic and tail-skin temperatures were monitored for 60 min. There were no significant differences in mean ambient or tail-skin temperatures between groups belonging to the same ambient condition. Colonic temperatures under the 1 bar conditions were 1.5-2 degrees C lower in the 3.5 g/kg ethanol group than in the saline and 1.5 g/kg ethanol groups, while no significant differences were observed between the groups at 48 bar. Comparisons of the colonic temperatures at the end of the observation period, i.e., 60 min after administration of ethanol, demonstrated that their values at 48 bar were significantly lower than at 1 bar after saline, significantly higher after 3.5 g/kg ethanol and identical across conditions in the 1.5 g/kg groups. The results suggest that high ambient pressure may counteract rather than potentiate the hypothermic effect of ethanol. PMID- 1924511 TI - Cholinergic modulation of oral activity in drug-naive and chronic haloperidol treated rats. AB - The cholinergic agonists pilocarpine, physostigmine, oxotremorine, and arecoline were administered IP at various doses to rats. Oral activity was assessed in these animals with a computerized video analysis system that determined the number and form of jaw openings and closings (computer scored movelets "CSMs"). The different cholinergic drugs produced distinctive changes in the number of CSMs at various amplitudes and in the frequency distribution of CSMs as determined by fast fourier analysis. Rats treated for 28 weeks with haloperidol showed a previously described, late onset oral dyskinesia characterized by increases in small amplitude CSMs, decreases in CSM slope, increased energy at the 1-3 Hz range and decreased energy at the 5-7 Hz range. Administration of pilocarpine (1.0 mg/kg) reversed all of these effects, while the anticholinergic drug, scopolamine (0.05 mg/kg), had no effect. These results indicate that different cholinomimetics can uniquely alter oral activity in rats and that symptoms of late onset, neuroleptic-induced oral dyskinesia are modified by a cholinergic agonist. PMID- 1924512 TI - HAS and LAS rats respond differentially to behavioral effects of ethanol, pentobarbital, chlorpromazine and chlordiazepoxide. AB - The drug discrimination paradigm (DD) was used to evaluate differences in performance of rats selectively bred for differential sensitivity to the hypnotic effects of ethanol. Tenth generation high-alcohol sensitive (HAS) and low-alcohol sensitive (LAS) rats were trained to discriminate between ethanol (1.0 g/kg, IP) and saline vehicle on a VR-5 schedule of reinforcement. The HAS strain was more sensitive to the discriminative effects of ethanol than the LAS strain, but the magnitude of difference was much smaller than the differential sleep-time differences. The biphasic action of ethanol was differentially seen when the LAS animals exhibited increased activity during both DD and spontaneous motor activity measures and the HAS exhibited decreased activity during DD only. Pentobarbital and chlordiazepoxide but not chlorpromazine elicited the ethanol discriminative choice in both HAS and LAS strains. Response rates during DD indicated a dissociation of rate depressant effects and discriminative performance following ethanol. These findings are discussed in relationship to some current and future uses of selectively bred animal strains and DD for studying the effects of alcohol. PMID- 1924513 TI - Effect of 3-amino-1,2,4-triazole on ethanol-induced narcosis, lethality and hypothermia in rats. AB - It has been proposed that ethanol can be oxidized in brain via the peroxidatic activity of catalase and that centrally formed acetaldehyde may mediate several of the psychopharmacological actions of ethanol. The present study was designed to investigate the role of brain catalase in the mediation of ethanol-induced narcosis, hypothermia and lethality in rats. Rats were pretreated with the catalase inhibitor 3-amino-1,2,4-triazole (AT) or saline. Five hours later, animals in each pretreatment group received IP injections of ethanol (3 or 4 g/kg). Ethanol-induced narcosis was significantly attenuated in AT-pretreated rats compared to the saline control group. As well, AT pretreatments reduced significantly the lethal effect of these ethanol doses. However, AT-pretreated ethanol-injected animals significantly reduce their body temperature as compared to the saline-ethanol animals. Blood ethanol determinations revealed that AT did interfere with ethanol metabolism. AT inhibits significantly brain catalase activity at all doses used in this study. The results indicate a role for brain catalase in ethanol effects. Furthermore, they suggest that catalase may be involved in the oxidation of ethanol in brain and that centrally formed acetaldehyde may play a role in ethanol-induced narcosis and lethality, but not hypothermia. PMID- 1924514 TI - A comparative study of the behavioral effects of d-amphetamine and apomorphine in the rat. AB - A wide range of doses of d-amphetamine and apomorphine were injected into rats, in order to better characterize and compare dopaminergic agonist-induced behavioral effects. The study was carried out using a computerized technique for the quantification and analysis of various behavioral elements. Although both drugs increased motor activity and provided dose-dependent stereotyped responses, the whole pattern of behavior in the open field showed a different structure. d Amphetamine in doses that did not produce stereotyped responses induced a wide range of varied behavioral elements with increased frequency but decreased mean duration, while apomorphine induced a more restricted behavioral profile. Furthermore, a higher frequency of freezing reaction was observed after d amphetamine treatment in low doses but not after apomorphine treatment. Both drugs in high doses elicited a similar stereotyped syndrome characterized by repetitive movements of great duration, but at low doses the behavioral pattern was completely different. The apomorphine-induced syndrome was characterized mainly by moving and sniffing, interrupted by rearing, while the amphetamine induced syndrome by sniffing and moving, interrupted by standing and freezing. PMID- 1924515 TI - The effects of 6-OHDA-induced dopamine depletions in the ventral or dorsal striatum on maternal and sexual behavior in the female rat. AB - The effects of dopamine-depleting 6-OHDA infusions in the ventral or dorsal striatum on maternal and sexual behaviors were examined in female rats. Like sham operated controls, lactating rats receiving 6-OHDA in the ventral striatum built good nests, nursed the infants and showed maternal aggression toward strange intruders. By contrast, the lesioned females performed poorly in tests for pup retrieval, as reflected in greatly protracted retrieval latencies. There was no effect of ventral striatal DA depletions on proceptive and receptive elements of female sexual behavior, which was studied after lactation following ovariectomy and exogenous administration of ovarian hormones, but these animals did show an attenuated hyperactivity response to a low dose of amphetamine. Females with dopamine lesions in the dorsal striatum did not differ from controls with respect to maternal and sexual behavior, but they did show an enhanced hyperactivity response to amphetamine treatment. PMID- 1924516 TI - Clonidine enhances delayed matching-to-sample performance by young and aged monkeys. AB - Clonidine, an alpha-2 noradrenergic agonist, has been shown to alter cognitive performance in humans and animals. Included among the evidence are studies which differ in their conclusions regarding the question of whether clonidine administration improves delayed response (DR) performance by nonhuman primates. The present results indicated that clonidine administration to both young and aged monkeys results in a modest performance improvement as measured by one of the commonly employed versions of DR performance-delayed matching-to-sample (DMTS). The clonidine-induced enhancement of DMTS had a duration of at least 24 h in both age groups. PMID- 1924517 TI - Caloric vs. pharmacologic effects of ethanol consumption on activity anorexia in rats. AB - Food restriction, combined with access to a running wheel, produces "activity anorexia" (self-starvation) in rats. The relative effects of ethanol and propylene glycol on activity-maintained self-starvation were examined. Young male rats were provided with access to a running wheel while on a 22.5-h food deprivation schedule. One-third were concurrently provided with a 7% solution of ethanol, one-third with a (pharmacologically weak) 7% solution of propylene glycol, and one-third with water. Results indicated that neither survival rate nor running activity were affected significantly by ethanol consumption, relative to water-drinking controls. However, increased survival rates and decreased activity were observed for those animals which consumed propylene glycol. Antagonistic effects of ethanol on energy metabolism, stress responses, and the preservation of body weight are considered in light of these findings. PMID- 1924518 TI - Differential effects of antidepressant treatments on fenfluramine-induced increases in plasma prolactin and corticosterone in rats. AB - Intravenous administration of 5-HT releasing agent, fenfluramine, to rats produced increases in plasma prolactin and corticosterone concentrations. Short term or long-term treatment with either clorgyline or imipramine did not affect baseline levels of prolactin or corticosterone. On the other hand, short-term but not long-term lithium treatment significantly increased baseline levels of corticosterone but not of prolactin. Short-term treatment with lithium but not clorgyline or imipramine potentiated fenfluramine-induced increases in plasma prolactin but not corticosterone. On the other hand, long-term treatment with clorgyline but not imipramine or lithium attenuated fenfluramine's effect on plasma prolactin but not on corticosterone. These findings demonstrate differential effects of antidepressant treatments on fenfluramine-induced increases in plasma prolactin and corticosterone in rats and are consistent with several other clinical and animal studies demonstrating dissimilar actions of different antidepressant treatments on two different 5-HT-mediated neuroendocrine functions. PMID- 1924519 TI - Behavioral effects of intrastriatal caffeine mediated by adenosinergic modulation of dopamine. AB - Although caffeine is generally classified as a psychomotor stimulant, the neurotransmitter systems mediating its effect on behavior have not yet been established. Mounting evidence suggests possible involvement of adenosinergic and/or dopaminergic (DA) systems. To evaluate these possibilities, four experiments examined circling behavior in rats following unilateral intrastriatal microinjections of: 1) caffeine alone; 2) the adenosine agonist, 2 chloroadenosine (2-CADO) alone; 3) caffeine with 2-CADO pretreatment; and 4) caffeine with pretreatment of the DA receptor antagonist, cis-flupenthixol. Each experiment consisted of seven test sessions; the first and seventh were preceded by no treatment, the second and sixth by control microinjections (saline or cis flupenthixol) and the third, fourth and fifth by drug microinjections. Results showed that 10.0 and 20.0 but not 1.0 micrograms of caffeine produced a significant contraversive bias in circling behavior, while 2.0 and 5.0 but not 1.0 microgram doses of 2-CADO produced significant ipsiversive circling. Rats pretreated with central 2-CADO or cis-flupenthixol (in doses that did not influence circling bias when administered alone) prior to caffeine (10.0 micrograms) failed to exhibit a contraversive bias. Taken together, the present studies provide compelling support for the suggestion that the motor effects of intrastriatal caffeine are mediated by the antagonism of endogenous adenosine which, in turn, functionally increases DA. PMID- 1924520 TI - The AIDS patient: a historical perspective on the physician's obligation to treat. PMID- 1924521 TI - Medicine and the social contract. PMID- 1924522 TI - Cynicism and medical education. PMID- 1924523 TI - Serendipity can be nudged. PMID- 1924525 TI - On needle sticks and other metaphors. PMID- 1924524 TI - Anton Chekhov's doctors. PMID- 1924526 TI - The healer's Achilles' heel. PMID- 1924527 TI - W. Larimer Mellon, Jr.: in the spirit of Albert Schweitzer. PMID- 1924528 TI - Biomedical research and its application--a paradox. PMID- 1924529 TI - Woman--greatest plague of all? PMID- 1924530 TI - The wounds of the bull. PMID- 1924531 TI - Facing medicine's moral and ethical questions. PMID- 1924532 TI - Too many specialists? PMID- 1924533 TI - On withholding information from patients. PMID- 1924534 TI - Medicine and the quest for certainty. PMID- 1924535 TI - Nurses to the rescue: Philippine experience. PMID- 1924536 TI - Towards a new paradigm for health. PMID- 1924537 TI - New IPPF statement on the diagnosis of pregnancy. PMID- 1924539 TI - The role of the nurse in the promotion of children's rights. PMID- 1924538 TI - Teamwork in nursing and health care delivery. PMID- 1924540 TI - Report of the IPSM working party on low- and medium-energy x-ray dosimetry. Institute of Physical Sciences in Medicine. AB - New values of the factors required to convert the reading of a radiation dosemeter calibrated in terms of air kerma (or exposure) into absorbed dose to water for medium-energy x-radiation were given in a code of practice published by the IAEA in 1987. These are not considered to possess sufficient support from other sources. It is therefore recommended that the F-factors given in ICRU Report 23, and incorporated into the current HPA code of practice (1983), should continue to be used. Values of backscatter factors for low-energy x-radiation (below 140 kV or 10 mm Al HVL) in Supplement 17 of the British Journal of Radiology appear to be inaccurate. New values based on Monte Carlo calculations, and supported by new experimental data, are given for use in radiotherapy. PMID- 1924541 TI - Ultrasound attenuation and texture analysis of diffuse liver disease: methods and preliminary results. AB - A study was performed to find and test quantitative methods of analysing echographic signals for the differentiation of diffuse liver diseases. An on-line data acquisition system was used to acquire radiofrequency (RF) echo signals from volunteers and patients. Several methods to estimate the frequency-dependent attenuation coefficient were evaluated, in which a correction for the frequency and depth-dependent diffraction and focusing effects caused by the sound beam was applied. Using the estimated value of the attenuation coefficient the RF signals themselves were corrected to remove the depth dependencies caused by the sound beam and by the frequency-dependent attenuation. After this preprocessing the envelope of the corrected RF signals was calculated and B-mode images were reconstructed. The texture was analysed in the axial direction by first- and second-order statistical methods. The accuracy and precision of the attenuation methods were assessed by using computer simulated RF signals and RF data obtained from a tissue-mimicking phantom. The phantom measurements were also used to test the performance of the methods to correct for the depth dependencies. The echograms of 163 persons, both volunteers and patients suffering from a diffuse liver disease (cirrhosis, hepatitis, haemochromatosis), were recorded. The mutual correlations between the estimated parameters were used to preselect parameters contributing independent information, and which can subsequently be used in a discriminant analysis to differentiate between the various diseased conditions. PMID- 1924542 TI - Impact of gamma camera parameters on imaging performance, evaluated by receiver operating characteristic (ROC) analysis. AB - The relationship between gamma camera variables (total counts in image, collimator type, etc) and diagnostic imaging performance was quantitatively investigated using receiver operating characteristic (ROC) curve analysis. A College of American Pathologists (CAP) liver phantom was used with a 99Tcm flood source to generate anterior and lateral liver images containing 'cold lesions'. These images were interpreted by four nuclear medicine physicians, and the areas under the corresponding ROC curves computed. These medicine physicians, and the areas under the corresponding ROC curves computed. These areas were taken as a quantitative estimate of the imaging performance of the system. The average area under the ROC curve for the four physicians reading the same 'standard' image six times was computed to be 66.8 +/- 5.8. Experiments were performed to show the effect on diagnostic performance of (i) increasing the total image counts from 200k to 2000k, (ii) varying the phantom-to-collimator separation from 0 to 8 cm and (iii) changing the collimator type. In all cases, data were generated which demonstrated the quantitative improvement (or deterioration) resulting from these changes. These data may be used in the design of clinical imaging protocols, for which choices have to be made for each gamma camera variable. PMID- 1924543 TI - Finite-difference time-domain calculations of SAR in a realistic heterogeneous model of the head for plane-wave exposure from 600 MHz to 3 GHz. AB - This paper presents finite-difference time-domain (FDTD) calculations of the specific energy absorption rate (SAR) in a fine-scaled, heterogeneous, realistic model of the head for frequencies ranging from 600 MHz to 3 GHz. The phantom has been derived from an atlas of cross-sectional anatomy. The cell size is 3.2 mm which results in a 120,000 cell head model comprising brain, bone/fat, muscle, skin, blood, air and eye humour, lens and sclera. Irradiation from the front and side for plane-wave exposure of an adult and an infant are considered. PMID- 1924544 TI - Ideal versus human observer for long-tailed point spread functions: does deconvolution help? AB - The ideal observer represents a Bayesian approach to performing detection tasks. Since such tasks are frequently used as a prototype tasks for radiological imaging systems, the detectability measured at the output of an ideal detector can be used as a figure of merit to characterize the imaging system. For the detectability achieved by the ideal observer to be a good figure of merit, it should predict the ability of the human observer to perform the same detection task. Of great general interest, especially to the medical community, are imaging devices with long-tailed point spread functions (PSFs). Such PSFs may occur due to septal penetration in collimators, veiling glare in image intensifiers or scattered radiation in the body. We have investigated the effect that this type of PSF has on human visual signal detection and whether any improvement in performance can be gained by deconvolving the tails of the PSF. For the ideal observer, it is straightforward to show that the performance is independent of any linear, invertible deconvolution filter. Our psychophysical studies show, however, that performance of the human observer is indeed improved by deconvolution. The ideal observer is, therefore, not a good predictor of human observer performance for detection of a signal imaged through a long-tailed PSF. We offer some explanations for this discrepancy by using some characteristics of the visual process and suggest a standard of comparison for the human observer that takes into account these characteristics. A look at the performance of the non-prewhitening (npw) ideal observer, before and after deconvolution, also brings some good insight into this study. PMID- 1924546 TI - Observation of NMR phosphate echoes from solid bone. PMID- 1924545 TI - Dose-response characteristics of a ferrous-sulphate-doped gelatin system for determining radiation absorbed dose distributions by magnetic resonance imaging (Fe MRI). AB - The nuclear magnetic resonance (NMR) longitudinal relaxation rate R1 dose response characteristics of a ferrous-sulphate-doped chemical dosimeter system (Fe MRI) immobilized in a gelatin matrix were explored. Samples containing various concentrations of the FeSO4 dosimeter were irradiated to absorbed doses of 0-150 Gy. R1 relaxation rates were determined by imaging the samples at a field strength of 1.5T(1H Lamor frequency of 63.8 MHz). The response of the system was found to be approximately linear up to doses of 50 Gy for all FeSO4 concentrations studied (0.1-2.0 mM). Changing concentrations in the range of 0.1 0.5 mM affected both the slope and intercept of the dose-response curve. For concentrations of 0.5-2.0 mM, the slope of the dose-response curves remained constant at approximately 0.0423 s-1 Gy-1 in the dose range of 0-50 Gy. However, the intercept of the curve continued to increase in that region, as expected, because of the additional paramagnetic ions. The reproducibility of the absorbed dose estimates for measurements made over a 22 cm field of view was found to be 5% in the range of 20-50 Gy (an uncertainty of 0.81 Gy on average), decreasing to approximately 10% in the dose range of 5-10 Gy. PMID- 1924547 TI - The measurement and routine checking of mammography x-ray tube kV. PMID- 1924548 TI - Renal medullary organic osmolytes. AB - Sorbitol, inositol, GPC, and betaine are the predominant organic osmolytes in renal medullary cells. They protect the cells from harmful effects of the high interstitial NaCl and urea concentrations that occur normally in the renal medulla with operation of the urinary concentrating mechanism. Their levels correlate with extracellular NaCl concentration and, in the case of GPC, also with urea. Sorbitol is synthesized from glucose in a reaction catalyzed by aldose reductase. Inositol and betaine are transported into the cell. Glycerophosphorylcholine synthesis is dependent on choline. The transcription of aldose reductase and the transport of betaine and inositol are regulated, dependent on the degree of hypertonicity. Normal organic osmolyte regulation contributes to the survival and growth of medullary cells in their hyperosmolal environment, and defective regulation can damage them. PMID- 1924549 TI - Immunologic system in the respiratory tract. PMID- 1924550 TI - Physiological adaptation to high altitude: oxygen transport in mammals and birds. PMID- 1924551 TI - Vitamin A metabolism: new perspectives on absorption, transport, and storage. PMID- 1924552 TI - Fetal lung liquid: secretion and reabsorption. PMID- 1924553 TI - Association of Chairmen of Departments of Physiology annual questionnaire results. PMID- 1924554 TI - Genetic and physical mapping of the Rhodobacter sphaeroides photosynthetic gene cluster from R-prime pWS2. AB - Plasmid pWS2 is an R68.45 chimera originally isolated as an R-prime which complemented the Rhodobacter sphaeroides bch-420 allele. Our experiments have shown that pWS2 is also able to complement a wide range of R. sphaeroides pigment and photosynthetic mutants employing nitrosoquanidine, transposon or insertion generated mutations effecting puhA, puc, puf, cycA, bch, and crt genes. A combination of orthogonal-field-alternation gel electrophoresis, transverse alternating field gel electrophoresis, and conventional electrophoresis have been used to estimate the size of pWS2 at congruent to 168.3 +/- 3.5 kb. A restriction map of the congruent to 109 kb of R. sphaeroides insert DNA was generated by partial and complete restriction endonuclease digestion coupled with Southern hybridization analysis using either gene-specific or junction fragment probes. Genes encoding bacteriochlorophyll (Bchl)-binding proteins (pufBALMX, pucBA, and puhA), cytochrome c2 (cycA), and enzymes involved in Bchl (bch) and carotenoid (crt) biosynthesis have been shown to reside within a contiguous 53-kb region of the R. sphaeroides DNA present on pWS2. The puf operon lies at one end of the 53 kb segment, while the genes puhA, cycA, and pucBA, the latter two of which are located within congruent to 12.0 kb of each other, define the other end of this 53-kb region. The genetic and physical mapping data provided in this paper are discussed in terms of the similarities and differences in the organization of the photosynthetic gene cluster between R. sphaeroides and other photosynthetic bacteria as well as highlighting the use of pWS2 in studies of photosynthetic gene structure and function. PMID- 1924555 TI - Control of Enterococcus faecalis sex pheromone cAD1 elaboration: effects of culture aeration and pAD1 plasmid-encoded determinants. AB - Aeration of plasmid-free Enterococcus faecalis strains resulted in an 8- to 16 fold decrease in sex pheromone cAD1 activity in culture filtrates. Levels of two unrelated pheromones, cPD1 and cAM373, were unaffected by culture aeration. Aeration also resulted in a decrease in the expression of conjugative transfer functions observed in cells containing pAD1 traB mutations, verifying a link between traB function and pheromone "shutdown." Tests with a series of pAD1 mini plasmids indicated that the product of the traB gene was involved in, but not sufficient for, pheromone shutdown; the cooperation of one or more other gene products encoded within the pheromone response control region was required. PMID- 1924556 TI - Cloning and characterization of two plasmids from Bacillus thuringiensis in Bacillus subtilis. AB - Bacillus thuringiensis subspecies israliensis plasmids pTX14-1 and pTX14-3 were cloned and analyzed by Southern blot hybridization for their replication mechanism in Bacillus subtilis. The cloning of pTX14-1 into the replicon deficient vector pBOE335 showed the usual characteristics of single-stranded DNA plasmids, i.e., it generated circular single-stranded DNA and high molecular weight (HMW) multimers. The other plasmid, pTX14-3, behaved differently; it generated neither single-stranded DNA nor HMW multimers. Treatment with rifampicin did not result in the accumulation of single-stranded DNA. However, deletion of an EcoRI-PstI fragment resulted in the accumulation of both single stranded DNA and HMW multimers. From various deletion derivatives, we have mapped the minus origin and the locus responsible for suppression of HMW multimer formation. Full activity of the minus origin and of the locus suppressing HMW formation was only observed on the native replicon, indicating a coupling to the plus strand synthesis. PMID- 1924558 TI - Characterization of Chinese hamster ovary cells stably transformed by a plasmid with an inducible APRT gene. AB - A plasmid was constructed by fusion of a selectable mammalian gene, hamster adenine phosphoribosyltransferase (APRT), to the Zn(2+)-inducible sheep metallothionein I (MT I) promoter. This plasmid was used to produce stable Chinese hamster ovary (CHO) cell transformants by electroporation to study the effects of induced gene expression on DNA-mediated transformation. The sheep MT Ia promoter was chosen for these experiments because it regulates gene expression differently than murine MT promoters, exhibiting low basal levels of gene expression in uninduced conditions. We have shown that in the absence of Zn2+, there is very low expression of a sheep MT I-APRT fusion gene in stable CHO cells transformants; induction of APRT mRNA and enzyme activity by Zn2+ produced a "threshold" response, from low basal levels to high induced levels, in Zn2+ responsive stable transformant clones. In electroporation experiments, transformation frequencies were unaffected by Zn2+ treatments during a preselection period, but the presence of Zn2+ during selection increased the recovery of stable transformant clones 8- to 10-fold. All stable transformants analyzed displayed Zn(2+)-inducible APRT enzyme activity. Our results indicate that stable mammalian cell transformants with inducible genes under regulation of the sheep MT I promoter should be useful, because of low basal and high induced expression, for studies in which modulation of transcriptional activity is required. PMID- 1924557 TI - The effect of plasmid copy number mutations on pT181 replication initiator protein expression. AB - Previous studies have shown that plasmid pT181 controls its replication by countertranscript-mediated regulation of the rate of synthesis of the pT181 initiator, RepC. In this study, the relation has been studied between plasmid copy number and RepC synthesis for a series of pT181 copy number mutants. For each mutant plasmid, the repC coding sequence along with its 5' regulatory region was translationally fused to the beta-lactamase structural gene on a vector plasmid unrelated to pT181. By means of these constructs, the effect of regulatory mutations on the initiator synthesis could be measured at constant copy number. With one exception, the mutant control regions showed elevated beta lactamase activity in comparison to the wild-type. However, the relative increase was not very well correlated with the copy number of the corresponding mutant plasmid. The possibility is considered that factors such as DNA secondary structure may have important ancillary effects on the regulation mechanism. PMID- 1924559 TI - New shuttle vectors for Haemophilus influenzae and Escherichia coli: P15A-derived plasmids replicate in H. influenzae Rd. AB - With the aim of identifying new plasmids useful for molecular cloning in Haemophilus influenzae, several P15A-derived plasmids were tested for their ability to transform H. influenzae Rd. The four plasmids tested, pACYC177, pACYC184, pSU2718, and pSU2719 were all able to establish in H. influenzae Rd. The plasmids were stable, could be purified by standard protocols, and were compatible with a plasmid carrying the RSF0885 origin of replication. PMID- 1924560 TI - Synthetic polymers seeded with chondrocytes provide a template for new cartilage formation. AB - A new approach for tissue creation using synthetic biocompatible and biodegradable polymers as templates onto which cells are seeded is presented. This report concerns the generation of homogeneous plates of stable mature cartilage in vivo. The delivery of chondrocytes on synthetic polymers configured to provide a large surface area for cell attachment and thus to allow cell function and survival by diffusion of nutrients has resulted in the creation of macroscopic plates of up to 100 mg of new cartilage subcutaneously in 19 of 21 animals. The approximate dimensions and configuration of the original templates were maintained as new cartilage was formed and the polymers resorbed. PMID- 1924561 TI - Aesthetic refinements in genioplasty: the role of the labiomental fold. AB - The vast majority of patients requesting aesthetic enlargement of their chins have a class II skeletal deformity secondary to a small mandible. Class II skeletal patterns are frequently associated with abnormalities of lower face height, which, in turn, affect labiomental fold morphology. Of 68 patients who were to undergo sagittal advancement of their chins, 88 percent were considered to have abnormal labiomental fold morphology that was closely related to abnormalities of the facial height. Patients with decreased lower face height (40 percent) had exaggerated, deepened folds with acutely closed angles between the lower lip and chin pad, whereas those with increased lower face height (25 percent) had shallow, effaced folds. Patients with normal lower face height had variable fold morphology. Isolated sagittal advancement and/or simultaneous advancement and vertical shortening deepened the labiomental fold and closed the angle between the chin pad and lower lip. Simultaneous advancement and lengthening tended to deemphasize the fold, making it appear less deep in 20 of 34 patients, or at least mitigated further accentuation of the fold in 14 of 34 patients. Altered labiomental morphology and its relationship to the class II skeletal deformity is discussed. Treatment planning decisions are suggested, taking into account labiomental aesthetics and how they are influenced by advancement genioplasty. PMID- 1924562 TI - Nonsurgical repair of perinasal skin defects. AB - Immediate reconstruction of full-thickness skin defects after cancer surgery is a commonly accepted surgical principle used to preserve function and minimize cosmetic deformity. Healing by secondary intention, however, offers the advantages of optimal cancer surveillance, simplified wound management, and avoidance of reconstructive procedures with their associated costs and potential complications. Accurate prediction of the course of wound healing, and thereby the final functional and cosmetic result, would allow a rational approach to selection of patients for surgical or nonsurgical repair. We observed 282 patients with full-thickness perinasal (glabella, medial canthus, dorsum, sidewall, tip, ala, philtrum, alar base, and nasolabial fold) skin defects after Mohs' surgery and documented a variety of parameters affecting wound healing, including location, depth, and size of the wound. Patients were examined at intervals, and a final determination regarding cosmesis and function was made at 6 months or later. We conclude that the most important considerations in predicting the final functional and cosmetic result include location by subunit, followed by size and depth of the wound. PMID- 1924563 TI - Aesthetic resection of the submandibular salivary gland. AB - This paper analyzes some pathologies of the submandibular salivary gland that present a special interest for facial aesthetic surgeons. Even up-to-date techniques to correct the aesthetic deformities of the submandibular and cervical regions can be disappointing when the patient presents an increasing volume or ptosis of the submandibular salivary gland. Sometimes, even though the submandibular gland has not been preoperatively identified, it may become evident postoperatively, compromising the submandibular and cervical contour because the musculocutaneous flaccidity has been corrected and the fatty tissue present in this area has been eliminated. A personal approach is presented to treat the ptosis or the submandibular salivary gland enlargement that compromises rhytidoplasty results. A partial resection of the superficial part of the gland is suggested to treat some cases of ptosis or enlargement of the submandibular salivary gland. PMID- 1924564 TI - Periareolar reduction mammaplasty. AB - This paper examines the technique of periareolar reduction mammaplasty. Periareolar reduction mammaplasty is a less aggressive procedure than traditional techniques. It preserves a greater number of central glandular lobules, as well as the papillary artery and nerve. It can be performed under local anesthesia, and the area to be anesthetized is smaller because the amount of breast tissue to be resected is reduced. The sutures required number less than a third of those used for conventional techniques, and operative time is shorter. The greatest advantage is the inconspicuous periareolar scar left, combined with an acceptable result for both surgeon and patient. PMID- 1924565 TI - The effect of epinephrine on blood loss during suction lipectomy. AB - In a prospective, double-blind, controlled study on 26 consecutive patients who underwent suction lipectomy, the injection of epinephrine (1:250,000, 1:500,000, or 1:1,000,000) was not found to decrease fluid/blood loss when compared with saline injection or no injection at all. Since our study fails to support the use of epinephrine to lessen fluid/blood loss during suction lipectomy, we have abandoned its use in that procedure. PMID- 1924566 TI - Determination of preexcision surgical margins of melanomas from fixed-tissue specimens. AB - The shrinkage of cutaneous surgical specimens of 199 malignant melanomas was analyzed. A formula was derived that makes it possible to calculate the in vivo (preexcision) specimen diameter from the in vitro (fixed-tissue) specimen diameter. The age of the patient was found to significantly influence specimen shrinkage and was incorporated into this shrinkage formula. The calculated in vivo specimen diameter was then used to determine the width of the in vivo surgical margins with reasonable accuracy. Thus this method permits calculation of the width of surgical margins from fixed-tissue specimens. PMID- 1924567 TI - Is iliac node clearance necessary for stage II melanoma? AB - In a retrospective review (1970-1983), survival following block dissection of the groin was compared in two groups with clinical stage II melanoma. Twenty patients under one surgeon had ilioinguinal (high) block dissection, and 22 patients under another surgeon had inguinal (low) block dissection. The high block 5-year survival was 40 percent, and the low block 5-year survival was 35 percent. There was no statistical difference between groups on life-table or log-rank test analysis. It is concluded that the extent of groin dissection has no effect on survival of stage II melanoma. PMID- 1924568 TI - The extended pectoralis major myocutaneous flap: uses and indications. AB - The vascular territory of the pectoralis major muscle and overlying skin was studied by selective intraarterial dye injections in fresh cadavers. The area of skin overlying the anterior chest and abdominal wall beyond the limits of the pectoralis major muscle that can be elevated as an extended myocutaneous flap was determined. The cadaver injections were evaluated to determine the size and shape of the skin island used to reconstruct defects of the head, neck, and upper trunk with an extended skin paddle off the pectoralis major muscle. Pectoralis muscle flaps with variously shaped skin paddles, some extending beyond the limits of the muscle, were used in 27 patients to cover large soft-tissue defects of the upper thorax, face, and floor of the mouth and as a skin tube to reconstruct the cervical esophagus. The size of the skin paddle ranged from 5 x 7 cm to 26 x 16 cm. All flaps survived completely, and there were no major donor-site complications. PMID- 1924569 TI - Triphalangism in thumb polydactyly: an anatomic study on surgically resected thumbs. AB - Surgically resected thumbs in preaxial polydactyly were submitted to anatomic dissection to detect a triphalangeal thumb. Radiologically, two particular categories of thumbs with duplication at the metacarpophalangeal joint were seen. The surgically excised thumbs of either the radial or the ulnar member were preserved for dissection. Depending on the number of phalanges as well as on osteocartilaginous structures, the thumbs were classified into three groups. In the first group, the thumbs consisted of three phalanges but had absent joint formation between the phalanges and metacarpal. The second group consisted of three phalanges with two well-formed joints between them. The third group of thumbs also had three phalanges but had only one interphalangeal joint between them. In all three groups, morphologic features and clinical criteria are discussed. PMID- 1924570 TI - Second toe wrap-around flap. AB - The microsurgical second toe wrap-around technique is an ideal treatment option for reconstruction of the distal half of the finger with circumferential loss of skin and nail associated with an uninjured proximal interphalangeal joint and an intact insertion of the flexor digitorum superficialis tendon. Follow-up of 13 flaps in 10 patients from 1986 to 1989 demonstrates rapid and adequate functional recovery as well as satisfactory aesthetic appearance in all patients. PMID- 1924571 TI - The correlation of skin blood flow with age, total cholesterol, hematocrit, blood pressure, and hemoglobin. AB - Normal skin blood flow at the deltoid region in 55 men whose ages ranged from 20 to 72 years was measured by the xenon-133 clearance method. In addition, the correlation of skin blood flow with age, systolic blood pressure, total cholesterol, hematocrit, hemoglobin, and total protein was analyzed by multiple regression analysis. The following results were obtained. Normal skin blood flow was found to decrease with increase in age, total cholesterol, and systolic blood pressure and showed a tendency to increase with elevation in hematocrit and hemoglobin values. Of the six parameters examined in the present study, the parameter that showed the strongest correlation with skin blood flow at the deltoid region was age, followed in decreasing order by total cholesterol, hematocrit, systolic blood pressure, and hemoglobin. It could therefore be concluded that age is the most reliable factor in clinically estimating skin blood flow. Furthermore, inasmuch as total cholesterol, hematocrit, systolic blood pressure and hemoglobin values also were correlated with skin blood flow, these values also should be taken in account in the synthetic evaluation of skin blood flow. It was skin blood flow at the deltoid region that was strongly correlated with age. This was followed by systolic blood pressure, hematocrit, and hemoglobin. Total cholesterol showed a weak correlation with age, but total protein did not demonstrate any correlation with skin blood flow and age. The results of the present study show that skin blood flow would be poor in the elderly and in patients with arteriosclerosis, hypertension, and anemia. Since it is suggested that the wound-healing process is delayed in such patients, utmost care should be exercised in treating their wounds. PMID- 1924572 TI - Vasospasm and platelet deposition in human arteries: effects of topical methylene blue. AB - Vasodilation of small blood vessels is controlled in part by the endothelium derived relaxing factor (EDRF), which also inhibits platelet adhesion. Methylene blue (MB), which is occasionally applied directly to blood vessels during microsurgery to provide orientation and prevent torsion, is an irreversible inhibitor of the effects of endothelium-derived relaxing factor and may thereby augment both vasospasm and platelet responses. We have investigated the effects of the extravascular adventitial application of methylene blue on platelet deposition to human placental arteries (HPA) in the presence and absence of surgically induced vasospasm. A trend toward increased platelet deposition to human placental arteries was seen in each group but did not reach significance. The degree of platelet deposition to control human placental arteries suggests that the effects of methylene blue on platelet deposition may be dwarfed by the effects of surgical trauma and ischemia. PMID- 1924574 TI - The honor and responsibility of teaching in plastic surgery. PMID- 1924573 TI - Immunologic and ultrastructural changes during early rejection of vascularized bone allografts. AB - This investigation evaluated ultrastructural changes during the earliest phase of immunologic rejection of vascularized bone allografts in a genetically defined rat model. These results were correlated with the cell-mediated and humoral immunologic responses during this time period. Employing a model for heterotopic allograft transplantation, 33 rats divided into four categories were evaluated. Group I consisted of ungrafted (naive) Lewis and Brown Norway rats; group II consisted of Lewis-to-Lewis vascularized bone isografts; group III consisted of Lewis-to-Brown Norway vascularized bone allografts; and group IV consisted of Lewis-to-Brown Norway vascularized bone allografts in rats receiving cyclosporine (10 mg/kg/day). Experimental animals were sacrificed at 3, 5, and 7 days. Immunologic analysis was performed using a cell-mediated lymphocytotoxicity assay and a complement-dependent cytotoxic antibody assay. The results of this study show that rejection of vascularized bone allografts appears as early as 3 days postoperatively, with osteocytes and vascular endothelium being the first elements affected. This early rejection is probably a manifestation of the humoral response. All changes secondary to rejection were arrested by cyclosporine. PMID- 1924575 TI - Functional restoration: an old concept in new clothes. PMID- 1924577 TI - Reconstruction of both eyelids following electrical burn. AB - A case of severe electrical burn of the unilateral upper and lower eyelids is reported, together with the surgical technique of reconstruction. A 25-year-old man suffered an electrical burn on his left eyelids. On admission, his left upper and lower eyelids were subtotally necrotic. Total eyelid reconstruction was performed 2 1/2 months later. A chondromucosal graft taken from the nasal septum was utilized as the deep layer of the upper eyelid, which was covered by sliding down the remaining levator muscle and connective tissues to maintain the blood supply to the composite graft. The outer layer of the upper lid was reconstructed with a free split-thickness skin graft. The lower lid was reconstructed with a local flap lined with a free mucosal graft. This sandwich method using the levator muscle as a core was found useful for reconstructing both the upper and lower eyelids. PMID- 1924576 TI - Toward a classification of the chest and breast prior to immediate reconstruction. PMID- 1924578 TI - Soft-tissue masses of the temporal fossa. AB - An unusual problem, a soft-tissue mass of the left temporal fossa, is described. Differential diagnoses and pertinent studies for identifying the mass are reviewed. Our patient had a temporalis fascia defect with herniation of the temporal muscle causing his mass and associated symptoms. Surgical exploration, necessary for diagnosis, afforded us the opportunity for definitive treatment. PMID- 1924579 TI - Primary tuberculosis of the parotid gland. AB - A very unusual presentation of Mycobacterium tuberculosis in the parotid gland substance is described to suggest reexamination of the place of tuberculosis in the differential diagnosis of a parotid mass. In this patient, diagnosis was made postoperatively only by histologic examination of the excised specimen. When M. tuberculosis etiology is suspected, either clinically or at operation, culture confirmation should be tried, and a Mantoux test should be performed to complete the investigation. PMID- 1924580 TI - Congenital bifid sternum: repair in early infancy and literature review. AB - Sternal clefting is an unusual congenital anomaly that should be repaired in early infancy. Early surgery is facilitated by a highly compliant bony thorax. The surgical technique is described, including the (1) removal of a wedge at the confluence of the two lateral sternal bands to allow their apposition, (2) intraoperative assessment of pulmonary compliance and central venous pressure, (3) use of bilateral pectoral flaps, and (4) resulting avoidance of major costochondral stair-step osteotomies. The suggested age of repair is 1 to 4 weeks of age. PMID- 1924581 TI - Reconstruction of the crus helicis in mild microtia using a preauricular tag. AB - A preauricular tag accompanying a mild microtia was utilized in reconstruction of the anterior aspect of the helix and the crus helicis. We believe that three dimensional reconstruction of the crus helicis with a deep cymba conchae in microtia reconstruction is an important component in achieving a normal-looking auricle. PMID- 1924582 TI - Technique for correction of areola misplacement with no new scars. AB - A method of changing the absolute position of the areola if poor positioning occurs after surgery is described. This method uses tissue expansion as an intermediate step and in so doing allows movement with no new scars. There is no reason that medial, lateral, or superior malpositions could not be corrected in this way. Most breast reduction patients with bottoming out will not need this two-stage procedure if the areola is not too high in the beginning. PMID- 1924583 TI - Hyperbaric oxygen therapy in plastic surgery: a review article. AB - The most important effects of hyperbaric oxygen (HBO), for the surgeon, are the stimulation of leukocyte microbial killing, the enhancement of fibroblast replication, and increased collagen formation and neovascularization of ischemic tissue. Preoperative hyperbaric oxygen induces neovascularization in tissue with radionecrosis. Refractory osteomyelitis and necrotizing fasciitis appear to respond to adjunctive hyperbaric oxygen. Crush injury and compartment syndrome appear to benefit through preservation of ATP in cell membranes, which limits edema. Hyperbaric oxygen in burn injury permits shorter hospital stays, a reduced number of surgeries, and less fluid replacement. Skin grafts and flaps are reported to take more completely and more rapidly. The same mechanisms may apply in ischemic problem wounds such as infected diabetic extremities. Contraindications and side effects are described. Hyperbaric oxygen will not heal normal wounds more rapidly but may, under certain circumstances, induce problem wounds to heal more like normal ones. PMID- 1924584 TI - Surgical product failures. PMID- 1924585 TI - Choosing patients for aesthetic surgery. PMID- 1924586 TI - Joint microvascular transfer. PMID- 1924587 TI - Powered clysis: the rapid infusion of subcutaneous fluid. PMID- 1924588 TI - Postoperative hematomas associated with Toradol. PMID- 1924589 TI - Recurrent rash with staged, stacked polyurethane breast implants. PMID- 1924590 TI - Incorporating vascularized ribs in a latissimus dorsi myocutaneous flap. PMID- 1924591 TI - AACPS/ABPS/ASPRS/RRC retreat. PMID- 1924592 TI - Spray application of fibrin glue by a simple device. PMID- 1924593 TI - Another look at the eversion technique to improve frown lines. PMID- 1924594 TI - Iliac or cranial bone for secondary grafting of residual alveolar clefts. PMID- 1924595 TI - Medical alert bracelet and database for recording a patient's microsurgical reconstruction. PMID- 1924596 TI - Silicon levels in treated drinking water. PMID- 1924597 TI - [Alzheimer consultation--experience in diagnosis and therapy of organically induced psychiatric disorders]. AB - Some practical suggestions for the examination and treatment of patients with organic mental disorders are derived from the experience gathered in a special outpatient clinic. They refer to methods of obtaining necessary information, to the use of diagnostic criteria, and to the therapeutic possibilities in irreversible dementia. PMID- 1924598 TI - [Gerontopsychiatric patients in psychiatric facilities]. AB - The population of Vienna is relatively old. The structure of care and support for aged patients is described. The relative share of aged patients in all admissions to the large mental hospital is smaller than their share in total population. Reduction in the number of in-patients also included the group of patients over 65 years. The task force "Ubergangspflege" (i.e.: transitional nursing) prepares and supports the deinstitutionalization of recently admitted and of long-stay patients. Utilization of a regionalized out-patients psychiatric department shows differences between the age group 60-80 years and the group over 80 years. PMID- 1924599 TI - [Utilization of inpatient psychiatric care by patients with cerebral organic psychosyndrome. Cross-sectional analysis for 1988 exemplified by the Psychiatry Center in the routine health care of Frankfurt]. AB - All patients admitted to the Frankfurt Psychiatric Clinic suffering from organic psycho-syndromes were studied in a transversal survey. It was intended to evaluate the importance of clinical treatment within the psychiatric care system of a major city including various aspects of the diseases, psychosociological determinants and the continuation of service for these patients following clinical treatment. For the transversal survey a questionnaire was developed to record the psychopathological syndrome on admission, the order to referring patients to the clinic, outcome of treatment and service following clinical care. Patients suffering from organic psycho-syndromes represent a small quota of 4.2% according to the total admission rate. Within the group of elderly patients over 65 years of age it is remarkable that more cases with an affective psychosis were admitted than with organic psycho-syndromes. This small group of patients is in regard to interdisciplinary diagnostical and therapeutical proposals according to a high rate of multiple morbidity of distinct importance. The results of the presented study indicate the necessity to intensify the efforts of cooperation of psychiatric clinic, nursing homes and ambulatory care services for elderly patients with organic psycho-syndromes. PMID- 1924600 TI - [Admission of elderly patients in psychiatry: a study on the topic of "misplacement"]. AB - Misplacement of the old in psychiatry gains in special importance based on the absolute and relative increase of this population. 117 patients have been announced for admission to the psychogeriatric department of the Zwiefalten State Mental Hospital within six months. Admission of 47 patients did not happen mostly as the result of advising the announcing person or refusing because of pure social indication. The remaining 70 patients and further 16 emergency patients have been admitted to the department of them about two thirds with cerebro organic syndromes and one third with other mental diseases in old age. Mostly family doctors organized the hospitalisation, psychiatrists have been rarely engaged. In spite of severe reasons for hospitalisation, clinical treatment of patients with cerebro-organic syndromes turned out to be avoidable in more of the half of the cases, whereas it was justified in nearly 80% of the patients with other mental diseases in old age. As a whole, approximately the half of our admitted old patients would have not needed clinical treatment if there would exist enough qualified social care facilities, information deficits of the family doctors could be removed, and if psychiatrists would engage more in the treatment of mentally ill old persons. PMID- 1924601 TI - [Somatic diseases in inpatient treatment of psychiatric patients]. AB - This is a report on the frequency of somatic diseases in patients treated in regional psychiatric units (14471 courses of treatment). In 33.2% of all episodes (n = 4803) the psychiatrist diagnosed a somatic illness which was classified according to ICD-9. Most frequently quoted were diseases of the heart and the circulatory system (8.43% of all episodes), the nervous system (5.30%) and metabolic and endocrine disorders (5.17%). Distinct correlations between the rate of somatic morbidity and the variables age, sex and psychiatric diagnosis were found. In 4.04% of all episodes (n = 583) patients had to be transferred in a nonpsychiatric unit. 190 deaths were recorded, 18 of them in patients below the age of 65 years. The findings of this study show that hospitalized psychiatric patients are in need not only of psychiatric but also of medical care. A corroboration of this conclusion by further data is desirable. PMID- 1924602 TI - [Staff requirements for inpatient psychiatry. "Regulation of criteria and principles for personnel requirements in inpatient psychiatry" by the Federal Government in comparison with a personnel analysis generated by the clinic]. AB - A comprehensive analysis of the organization and personal setup was conducted at the Hans-Prinzhorn Clinic in Hemer, West Germany, from July to September 1989 after appropriate preparations that had taken about 12 months. The investigation method and the results are described. Besides the results themselves, planning and execution of this systematic study are significant in shaping the future development of this clinic. Later, and independent of our analysis, the Federal German Government promulgated a special regulation governing the setup of personal engaged in psychiatry, on 18 December 1990. The results of this regulation are compared with those obtained at our clinic. The results are practically always comparable or similar. Hence, minimum staff requirements in inpatient psychiatry were found to be near-identical as assessed by methodically different and independent analysis conducted at different times. PMID- 1924603 TI - Observation and theory in psychoanalysis: the self psychology of Heinz Kohut. AB - The development of self psychology by Heinz Kohut illustrates the influence of observational method on theory formation in psychoanalysis. In 1959 Kohut began to emphasize empathy and introspection over the traditional combination of free association and evenly suspended attention. This became an important part of a process of revision in psychoanalytic theory which culminated in self psychology. This paper demonstrates how and why that particular change in observational method influenced that particular revision of theory. PMID- 1924604 TI - The analyst's postgraduate development--rereading Freud and working theory through. AB - The authors believe that important aspects of a psychoanalyst's development can only be accomplished after the completion of training, that potential resistances to learning are not uncommon, and that the first five to ten postgraduate years are critical. A crucial acquisition of this developmental educational phase is a "theoretical identity," a personal theoretical synthesis which requires working through incompletely resolved transferences to Freud, to personal mentors and institutes, and to theory itself. The authors use the example of their own working through experiences while participating in a postgraduate Freud study group and show how a concurrent deepening of their theoretical identities contributed to their maturation as analysts and analytic teachers. PMID- 1924605 TI - Aspects of a dilemma of middle age: whether or not to place aged, failing parents in a nursing home. AB - A middle-aged person's involvement in making a decision about whether or not to institutionalize an aged parent whose physical and/or mental capacities have failed inevitably arouses intense feelings, memories, fantasies, and conflicts. Fantasies that equate putting the parent in a nursing home with abandonment and murder, as well as the narcissistic threat posed by seeing one's own future in a parent's deterioration, are common. The conflicts aroused may upset long-standing psychological balances. This paper explores ego, superego, id, and reality issues that are aroused as they were seen in the psychoanalysis and psychotherapy of several patients involved in making this decision. The importance of looking for the unique aspects of the conflicts set off in each individual facing this dilemma is stressed, as is the potential for countertransference responses. PMID- 1924606 TI - The tormentor and the victim in the nursery. AB - In our research nursery study of the emergence and vicissitudes of aggression, we had the opportunity to observe the unfolding of a particularly intense tormentor victim relationship between two boys aged seventeen and nineteen months. Through the large body of developmental information we have accumulated about both of these toddlers, we have been able to explore the infantile roots of what we view as the erotization of aggression. We see the fusing of aggression with libido as playing a crucial role in both normal and pathological personality formation. PMID- 1924607 TI - Cook-Medley hostility, anger, and the Type A behavior pattern in Finland. AB - According to research, hostility is a reliable predictor of coronary heart disease. Cook-Medley-defined hostility in particular has been seen as a significant precursor of coronary disease. It is important to specify the kind of hostility measured by the Cook-Medley scale. The present study examined the construct validity of the Cook-Medley scale for a sample of 219 university students in Finland, a country with a high incidence of coronary heart disease. The results supported the interpretation of the Cook-Medley scale primarily as a measure of cynicism and distrust. On the basis of our previous research, a subscale of the Cook-Medley scale was formed. This 9-item scale, a measure of Cynical Distrust, correlated positively with cynicism and negatively with trust. Moreover, the over-all pattern of correlations between the new 9-item factor, cynical distrust, and other variables assessing hostility, anger, and trust, was similar to the one obtained for our previous sample of students. It is suggested that this new 9-item scale is a shorter and more specific alternative to the longer Cook-Medley scale as a measure of cynical distrust. PMID- 1924608 TI - Higher trait- and state-anxiety in female law students than male law students. AB - To assess sex differences in anxiety, law students completed the State-Trait Anxiety Inventory prior to rating one-panel printed comics for humor level or copying text. Subjects completed the State-Anxiety subscale following the task. Although the humor-rating task was not more effective in reducing state anxiety than the copying task, scores on the anxiety subscales indicated that women law students scored consistently and significantly higher than men on both pretask measures and on the posttask measure. This finding is consistent with results from other studies in which other instruments were given. Analyses showed elevated anxiety and stress among preprofessional women; this supports the need for stress-management programs for law students. PMID- 1924609 TI - Coca-Cola, cancers, and coronaries: personality and stress as mediating factors. AB - A theory is presented relating the consumption of stimulant and depressant drugs to cancer and coronary heart disease, with stress/personality acting as an intermediary. The predictions from the theory that large-scale consumption of Coca-Cola would prevent cancer and promote coronary heart disease was tested and found to be supported by the results of a long-scale prospective study. Results replicate those from an earlier study using coffee as a stimulant drug. PMID- 1924610 TI - Development of the somatic response survey. AB - The goal in developing the Somatic Response Survey was to have a psychometrically sound, self-report instrument which could be used to assess patterns of normal physical responses during typical stressful situations. For a variety of reasons existing instruments were inappropriate for our goals. Three separate studies, involving 1623 students from 6 colleges, were conducted for data reduction, validation, and standardization of the Somatic Response Survey. Factor analyses indicated four meaningful factors: GastroIntestinal, MusculoSkeletal, Temperature Sweating, and Cardio-Respiratory. The factors collectively account for 91% of the variance and possess satisfactory internal consistency. The application of the Somatic Response Survey in both research and clinical settings is discussed. PMID- 1924611 TI - An experimental analogue examining effects of facilitative behaviors and subjects' warmth on students' perceptions of a counseling relationship. AB - This study examined the effects of students' self-reported ratings on warmth and a female counselor's facilitative behavior on scores measuring the subjects' perception of the counseling relationship. 75 subjects were categorized as warm, neutral, or cool and then randomly assigned to either a facilitative or nonfacilitative counselor condition. Scores from the Barrett-Lennard Relationship Inventory indicate significant main effects for both subjects' warmth and the therapist's facilitative behaviors. In addition, significant interactions between these variables were obtained. The specific interpretations of these results are discussed and methodological issues are identified for further research. PMID- 1924612 TI - Interpersonal dependency and locus of control as personality correlates among adult male alcoholics undergoing residential treatment. AB - The Interpersonal Dependency Inventory and the I-E Control Scale were administered to 22 male alcoholics in residential treatment. Contrary to prediction, subjects had normal dependency scores and external locus of control orientation. These findings contradict currently held assumptions about levels of dependence and the directionality of control orientation among inpatient alcoholics. Subjects were further examined for the influence of previous inpatient alcoholism treatment. Significant correlations were found between interpersonal dependency and control orientation scores for 14 alcoholics who were in residential treatment for the first time. Clinical implications for treatment concerning dependency factors and locus of control in inpatient populations are also discussed. PMID- 1924613 TI - Suicide and homicide among Native Americans: anomie or social learning? AB - Analysis of data for 12 areas of the Indian Health Services from the US Department of Health and Human Services yielded a rho of .61 between poverty and suicide for men and a significant rho of .65 for poverty with homicide rates. The Navajo area is an exception, raising for study questions about social disintegration. For the women, poverty was not significantly related to suicide or homicide rates, raising additional questions about social disintegration. PMID- 1924614 TI - Aggression: the dominant psychological response in children with malignant disease. AB - During the 11-yr. period of 1976 to 1986 leukemia or lymphoma treatment at the Children's Hospital, University of Helsinki was electively discontinued for the children in 90 different families. Of the 53 (59%) patients (mean age 6.4 yr. at diagnosis and 12.8 yr. at completion of questionnaires) who agreed to participate in the present study, 48 had acute lymphoblastic leukemia and five nonHodgkin lymphoma. Patients' and parents' impressions of the patients' psychological reactions during patients' prior chemotherapy were evaluated on parental and self ratings. Also, knowledge of and presumed causes of the malignancy were studied. Patients' reactions of aggression, depression, eating disorders, hypersensitivity, phobic anxiety, death anxiety, and night terror were examined using factor analysis. Aggression, in the form of irritation and anger, was displayed more often by girls than by boys. Patients of families suffering from stress were prone to exhibit aggression in the form of mood changes, irritation, and anger. Patients with disease-related knowledge, as opposed to those less well informed, were less depressed. Discrepancies between parents' and patients' thoughts about the origin of the malignancy were noted. PMID- 1924615 TI - Development of the male function profile/impotence questionnaire. AB - This paper describes three studies conducted to develop the Male Function Profile/Impotence Questionnaire as well as the psychometric properties of the instrument. The questionnaire is computer scored and, based on an interactional model, differentiates between organogenic and psychogenic causes for erectile dysfunction. Each subject is assigned one of 21 impotence profiles. Additional work-up recommendations are based on a breakdown and narrative describing all medical and psychological factors which bear on the subject's impotence. PMID- 1924616 TI - Correlations of temperament types, intensity of crisis at midlife with scores on a death scale. AB - 331 subjects completed the Keirsey-Bates Temperament Sorter and Dickstein's Death Scale and responded to an intensity of midlife crisis probe. Using a Pearson product-moment coefficient, weak but significant correlations were found for the introvert-sensor-thinker-judger temperament type on the Think and Anxiety subscales and the Think subscale for introvert-sensor-thinker-judger (ISTJ) temperament type. PMID- 1924617 TI - Smoking control and smoking rate: implications for worksite smoking cessation. AB - Amount of control of smoking at three comparable chemical plants was associated with smoking rates. Using a self-report survey, smoking rates were assessed at the three plants. Company authorities were asked about smoking control policy and the extent to which smoking was controlled at each of the three plants was observed. A judgment was made that one plant had a very strict smoking control policy while the other two had moderate policies of control. Smoking rate was then compared for each of the three companies. The company with the strongest smoking control policy had a significantly lower mean rate of smoking than the other two companies. Smoking control may serve to facilitate cessation on the worksite. PMID- 1924618 TI - A practitioner's notes on treating sexual deviance. AB - Considerable controversy exists regarding the treatment of sexual offenders. Often incarceration masks the environmental stimuli, resulting in not only early release but a false clinical prognosis for success. The paper looks at treatment strategies applicable to both the diagnostic and treatment components of sexual deviance. Specifically, what factors contribute to the symptoms associated with intense sexual urges and are there any viable treatment programs which carry over into the home world environment? PMID- 1924619 TI - Cognitive predictors of not-guilty verdicts in a simulated acquaintance rape trial. AB - Cognitive predictors, such as relatively accepting attitudes toward forcible date rape, helped identify self-reported sexually coercive college students and were expected to help identify students voting not guilty in a simulated acquaintance rape trial. To test this hypothesis college students self-administered in random order (1) an anonymous sex survey measuring attitudes toward forcible date rape, attitudes toward women, sexual experience, including victimization, sexual permissiveness, and sexual knowledge and (2) a trial survey based on a simulated acquaintance rape trial. Only gender and cognitive variables from the trial (e.g., being male, tending to blame the victim, and uncertainty about one's verdict) identified not guilty verdicts above chance expectancy. Thus, the hypothesis that the cognitive predictors measured here would help identify students voting not guilty in a simulated acquaintance rape trial was not supported. PMID- 1924620 TI - Gender differences in the attribution of causes for depressed feelings. AB - 30 male and 32 female undergraduates were asked to report over a 10-day period whether they had felt depressed and, if yes, what was causing their depressed feelings. As predicted from a sex-role framework, the men were more likely than the women to attribute the cause to academic concerns while the women were more likely than the men to attribute the cause to problems in interpersonal relationships. PMID- 1924621 TI - Breastfeeding and cognitive development of three-year-old children. PMID- 1924622 TI - The Sixteen Personality Factor Questionnaire--form E: experimental norms for mentally retarded adults. AB - Form E of the Sixteen Personality Factors Questionnaire (16 PF-E) was administered to 286 adults (168 men, 118 women) who resided in public facilities for the mentally retarded. Based on each subject's 16 primary-trait raw scores, standard sten scores were established for the subject population. Experimental norms for the 16 PF-E responses of mentally retarded adults are presented. PMID- 1924623 TI - Factor structure of the Motivation Assessment Scale for persons with mental retardation. AB - The rating scale used to assess the motivators of maladaptive behaviors in persons with mental retardation was the Motivation Assessment Scale. In the current study, we validated the factor structure of the scale on a sample of 118 subjects with predominately severe or profound mental retardation. They exhibited deviant behaviors such as self-injurious and tantrum behavior, aggression, and passivity. The results of the factor analysis with varimax rotation validated the assumptions of the developers of the scale that the motivators could be grouped into sensory, escape, attention, and tangible reinforcers. These four subscales are easily interpretable and should continue to provide valuable information. PMID- 1924624 TI - A test of Lester's depression paradox hypothesis of suicide. PMID- 1924625 TI - Effects of food deprivation on subjective effects and self-administration of marijuana in humans. AB - The effects of fasting on the intake and subjective effects of marijuana were studied in five marijuana smokers. A within-subjects design was used in which subjects smoked either active (0.8 and 3.6% THC) or placebo (0.0% THC) marijuana after eating normally or after fasting for 24 hr. Six experimental sessions were conducted in a randomized order. Each 3-hr. session consisted of two periods: a sampling period in which subjects took 4 controlled puffs from a cigarette of a given potency, followed about one hour later by a 30-min. self-administration period, in which subjects could smoke as much or as little of the sampled marijuana as desired. Subjective and physiological measures (i.e., carbon monoxide level and heart rate) were assessed before and 5, 20, and 60 min. after the four puffs during the sampling period. During the self-administration period, the number of puffs taken was recorded. Dose-dependent effects of marijuana, such as elevated heart rate and "high" ratings, were observed during the sampling period, but these effects of marijuana were not affected by the feeding manipulation. Subjects varied widely in their marijuana self-administration, but self-administration was not systematically affected by fasting. We conclude that an acute period of food deprivation does not affect the mood-altering effects of different potencies of marijuana. We could not adequately demonstrate whether fasting increases the reinforcing efficacy of marijuana, since self administration rate of active marijuana did not exceed that of placebo marijuana self-administration. PMID- 1924626 TI - The Sexual Desire Conflict Scale for Women: construction, internal consistency, and two initial validity tests. AB - The development of a 33-item Sexual Desire Conflict Scale for Women is described. The scale was designed to measure women's experiences of subjective discomfort and conflict in relation to sexual desire. 54 women participated: 18 survivors of childhood sexual abuse, 18 survivors of nonsexual trauma, 18 controls with no histories of trauma. Three factors accounted for 25.6, 12.9 and 7.6% of the variance. While no social desirability confounding was detected, the three groups had very different scores. Suggestions for research and clinical application are made. PMID- 1924627 TI - Body-image correlates of anxiety in a sample of male alcoholics. AB - Body-image testing of 10 male alcoholics with and 7 without anxiety disorders showed those with panic disorder had low barrier scores. Those with phobias emphasized their hearts and those with Posttraumatic Stress Disorder emphasized their backs. The barrier score correlated positively with both intensity of physical symptoms and with sense of blocked body openings. PMID- 1924628 TI - Measuring depressive mood in elderly Israeli: reliability and validity of the Depression Adjective Check Lists. AB - To establish the psychometric properties of the state form of the Depression Adjective Check List (DACL) with elderly Israeli, a 1981 Hebrew version of the DACL by Lomranz, Lubin, Eyal, and Medini, along with the Zung Self-rating Depression Scale and Cantril's Self-anchoring Striving Scale, were administered to 86 independently functioning elderly persons (35 men and 51 women) living in a home for the aged. Reliability estimates (alphas and test-retest) were moderate to high; validity estimates (concurrent and construct) were again moderate to high. It was concluded that the state form of the Depression Adjective Check List is suitable for use with elderly Israeli. PMID- 1924629 TI - On the stress/parasuicide or parasuicide/stress relationship. AB - The question of whether high stress leads to attempting suicide (parasuicide) or suicide attempters are more likely to report high stress was examined in a one year follow-up study of 98 persons, 47 of whom had attempted suicide. Cross lagged panel correlations between stress and parasuicide provided both concurrent and predictive validity that stress as measured by life changes leads to parasuicide. A high relationship between stress at baseline and stress at follow up provided support for the notion that some individuals experience chronic stress and that such individuals may be the ones at risk for future suicide attempts. PMID- 1924630 TI - Cognitive strategies and personality variables in adherence to exercise. AB - Variables associated with adherence to a 6-wk jogging program were examined in a group of 26 ++sedentary women, who received instruction and reinforcement for their efforts: one group of 16 received instruction in cognitive self-statements; the other group of 10 did not. Measures included a battery of psychological questionnaires, percentage of body fat, weight, height, and distance run in a 12 min. test. Subjects maintained logs in which they recorded frequency and duration of exercise. Follow-up data were collected at 6-wk. and 6=mo. postprogram. Initial compliance was related to scores on the Self-motivation Inventory, the Type H (Hard-driving) scale of the Jenkins Activity Survey, and the State Anxiety Scale. At 6-mo. follow-up, none of the measures were significantly correlated with exercise frequency. PMID- 1924631 TI - Assessment of Axis II personality disorders among female substance abusers. AB - 16 female substance abusers were assessed for the presence of personality disorders using two structured interviews and two self-report questionnaires. Although high prevalence of personality disorders was detected by each instrument, there was little agreement among the four methods for assessing these disorders. PMID- 1924632 TI - Relationships among burnout, death anxiety, and social support in hospice and critical care nurses. AB - The present study was undertaken to compare the occupational stress, levels of burnout, death anxiety, and the social support of a national sample of 376 hospice and critical care nurses. t tests indicated that critical care nurses reported significantly more occupational stress, showed higher burnout, and experienced more death anxiety than hospice nurses. The two nursing groups differed significantly when the three components of the Maslach Burnout Inventory were compared: hospice nurses reported feeling less emotional exhaustion, utilized the technique of depersonalization less frequently, and experienced a greater sense of personal accomplishment. The two nursing groups did not differ in social support when both the quantity and quality of that construct were examined. Pearson coefficients indicated positive associations between burnout and occupational stress and between burnout and death anxiety, with a negative relationship between burnout and social support. PMID- 1924633 TI - Simulation and dissimulation on alcoholism inventories: the ALCADD and the MAST. AB - A group of 36 normal college students was administered the Alcohol Addiction Test and Michigan Alcoholism Screening Test under three conditions. Significant contrasts between the scores obtained under the honest and simulated alcoholism conditions showed that normal subjects can simulate alcoholism on these inventories. PMID- 1924634 TI - Conventional diagnostic nomenclature versus multimodal assessment. AB - Standard psychiatric diagnoses (e.g., DSM-III-R) are compared with multimodal assessment and problem identification (i.e., BASIC I.D. formulations. Two case comparisons are presented as an heuristic to illustrate the way in which the multimodal framework promotes diagnostic precision and enhances clinical decision making. PMID- 1924635 TI - Relationships among defense style, existential anxiety, and religiosity. AB - 63 participants whose mean age was 26.8 yr. answered a questionnaire which measured defense style, existential anxiety, and religiosity. Defense style was generalized to existential concerns; repressors, who tend to avoid threatening stimuli, were likely to have less existential anxiety than sensitizers, who tend to approach threatening stimuli. Religiosity was related to neither defense style nor existential anxiety. It was suggested that religiosity was more influenced by socialization than by individual anxieties or personality variables such as defense style. PMID- 1924636 TI - Effects of amperozide in schizophrenia. An open study of a potent 5-HT2 receptor antagonist. AB - Ten male inpatients (aged 29 +/- 6 years) with a DSM-III diagnosis of schizophrenia participated in a 4-week open dose escalation study of amperozide, a novel 5-HT2 receptor antagonist. The maximum daily dose of amperozide was 20 mg. A close dose-plasma concentration relationship showed considerable interindividual variation in the steady-state plasma levels at a given dose. Approximately equal concentrations of amperozide and its metabolite, N deethylated amperozide, were seen in plasma. The prolactin levels were not increased during amperozide treatment. No changes occurred in hematological or other laboratory parameters. ECG showed changes in T-wave morphology and a prolongation of the QTc time. One patient was withdrawn from the trial due to aggravation of psychotic symptoms, and two patients had a brief, temporary discontinuation of the drug due to somatic illness. Six patients were improved during amperozide treatment, as assessed by the Clinical Global Improvement Scale. Among the responders the total CPRS was reduced by a mean of 64% and total BPRS score by a mean of 46%. Mild tremor was a frequent side effect, but other extrapyramidal symptoms were rare. Nausea was seen in six patients and of a more pronounced character in one patient. In general, the severity of the side effects increased with increasing doses of amperozide. PMID- 1924637 TI - Amphetamine derivatives induce locomotor hyperactivity by acting as indirect serotonin agonists. AB - Derivatives of amphetamine are potent releasers of both dopamine (DA) and serotonin (5-HT), but the relative contributions of DA and 5-HT release to the behavioral effects of these drugs have not been established. Previously, S-(+)3,4 methylenedioxymethamphetamine (S-(+)MDMA) was found to produce locomotor hyperactivity in rats which was dependent on 5-HT release. The present study found that MBDB (1.25, 2.5, 5.0 or 10.0 mg/kg), the alpha-ethyl derivative of MDMA that produces little or no direct DA release, also induced locomotor hyperactivity that lasted for greater than 60 min after the 5.0 and 10.0 mg/kg doses. MBDB produced spatial patterns of locomotor hyperactivity and suppression of exploratory activity (holepokes and rearings) very similar to the behavioral syndrome produced by MDMA. MBDB-induced hyperactivity was blocked by pretreatment with the selective 5-HT uptake inhibitor fluoxetine (2.5 or 10 mg/kg), suggesting that MBDB produced behavioral effects via uptake-carrier mediated release of 5 HT. Similarly, fluoxetine pretreatment blocked the locomotor hyperactivity produced by S-(+)3,4-methylenedioxyamphetamine (3.0 mg/kg) or p-chloroamphetamine (2.5 mg/kg), supporting a serotonergic basis for the action of these drugs. Tissue levels of 5-HT and its metabolite 5-HIAA were decreased 40 min after administration of S-(+)MDMA (3.0 mg/kg) or MBDB (5.0 mg/kg), and these decreases were prevented by fluoxetine pretreatment. S-(+)MDMA also produced a fluoxetine sensitive increase of tissue DA levels, suggesting that 5-HT release may indirectly result in increased DA release, although MBDB did not significantly increase DA levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1924638 TI - Cocaine toxicity: genetic evidence suggests different mechanisms for cocaine induced seizures and lethality. AB - While low doses of cocaine have been shown to decrease locomotor activity, and moderate doses produce marked increases in locomotor activity, high doses commonly produce seizures and, eventually, death. However, the biological mechanisms associated with cocaine-related death, as well as the contribution of seizure activity to death are poorly understood. This study examined the effects of a broad range of cocaine doses on acute occurrence of seizures and death in LS/Ibg (LS) and SS/Ibg (SS) mice. Large differences in sensitivity to cocaine induced seizures were seen, with ED50 values being 41.7 and 80.9 mg/kg for the SS and LS mice, respectively. Conversely, no significant differences in cocaine LD50 values were found, being 100.7 and 107.2 mg/kg for the SS and LS mice, respectively. That these lines of mice differ substantially in convulsant responses to cocaine, but show no difference in lethal response to this drug, supports the conclusion that cocaine causes death by mechanisms distinct from those which contribute to seizures. The distinction between cocaine-induced seizures and lethality in these lines may prove useful in elucidating the underlying mechanisms of these traits. In a subsequent study, the incidence of seizures in F1 and F2 generation mice from hybrid matings of LS and SS parents was not consistent with a single gene hypothesis, suggesting that multiple genes and receptors mediate seizurgenic responses to cocaine. Further, albino mice from the F2 generation did not show a significantly different incidence of seizures than non-albino mice, indicating that of the genes contributing to seizures following cocaine, none appear to be closely associated with the albino locus on mouse chromosome seven. PMID- 1924639 TI - Human aggressive responding during acute tobacco abstinence: effects of nicotine and placebo gum. AB - Aggressive and point maintained operant responding of heavy nicotine dependent male tobacco smokers were measured during five 25-min sessions conducted over an 8-h period. Responding under three tobacco abstinence conditions was compared to responding during a baseline condition of ad libitum smoking of the subject's preferred brand of cigarettes. The three tobacco abstinence conditions were: (1) placebo gum, (2) nicotine gum or (3) no gum. Under placebo and nicotine gum conditions, subjects were given two pieces of placebo or 2 mg nicotine gum to chew for 30 min prior to each session. Expired air carbon monoxide (CO) levels were measured at the end of each session to monitor smoking under baseline conditions and compliance with nonsmoking requirements under abstinence conditions. Aggressive responding was increased in no gum and placebo gum conditions, with the highest frequency of aggressive responding occurring under no-gum conditions. Aggressive responding during nicotine gum conditions did not differ from baseline ad libitum tobacco smoking. Point maintained responding was either not affected or decreased under placebo and no-gum conditions. These results provided objective data consistent with clinical reports of increased irritability among dependent tobacco smokers during acute tobacco abstinence. PMID- 1924640 TI - Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine. AB - The pharmacokinetic and pharmacodynamic effects of concomitant administration of alprazolam and fluoxetine were studied in this double-blind parallel study in 80 healthy, male volunteers. Subjects were randomly assigned to one of four treatment groups. Drug treatments consisted of 4-day regimens of 1 mg alprazolam four times daily, 60 mg fluoxetine every morning, 1 mg alprazolam four times daily and 60 mg fluoxetine every morning, and placebo four times daily. Psychomotor performance, mood status, and degree of sedation were evaluated at designated times. Combined administration of alprazolam and fluoxetine resulted in an approximate 30% increase in plasma alprazolam concentrations relative to plasma concentrations following the administration of alprazolam alone. There were no significant differences in fluoxetine or norfluoxetine plasma concentrations between the alprazolam/fluoxetine and fluoxetine treatments. Psychomotor decrements increased when fluoxetine was administered with alprazolam relative to alprazolam administration alone. Psychomotor performance of the fluoxetine treatment group was not significantly different from that of the placebo group. No significant changes were observed in mood status, and sedation was minimal in all treatment groups. As when any two psychoactive drugs are administered together, increased patient monitoring and patient education is recommended when alprazolam and fluoxetine are prescribed concurrently. PMID- 1924641 TI - Effects of tianeptine on the performance of a reaching movement in the cat. AB - Unlike other antidepressant drugs, tianeptine, when administered to cats at doses ranging from 1.2 to 5 mg/kg, produces an increase in arousal associated with longer sequences of immobile attentiveness. The present study analyses tianeptine induced effects on visuomotor performance. Cats were trained to perform a pointing movement towards a randomly moving spot of light. Following tianeptine treatment (5 mg/kg), visuomotor performance was totally disrupted. When 2.5 mg/kg tianeptine was used, the accuracy of performance was unaffected, whereas the latency of movement onset was considerably and consistently increased. On a number of occasions the movement took also longer to perform. Following lower doses (0.6-1.2 mg/kg), performance was rarely impaired; in contrast, an improvement of visuo-motor scores was observed. This improvement was mostly characterized by an increased accuracy and could be associated with shorter latencies of movement onset or shorter movement times. Desipramine, another antidepressant drug having few sedative effects, induced a clear delay of movement onset when first administered. Further injections did not produce any changes in the visuo-motor performance. These results are discussed in relation with other effects of tianeptine, in particular its facilitatory effect on attentional processes. PMID- 1924642 TI - Psychophysiological reactions during active and passive stress coping following smoking cessation. AB - This study investigated the effects of 9 days' smoking abstinence on psychophysiological stress reactions. The subjects were 40 female smokers; 20 of them intended to give up smoking in the course of the study, whereas the remaining 20 had no such intention. A first session was carried out before, a second and a third during days 3 and 9 of abstinence. The nonabstainers were tested at corresponding intervals. Each session consisted of a 30-min stress coping phase with relaxation phases before and after. While performing a rapid information processing task (RIP) the subjects had to sustain electrical shocks which were, according to instructions, but not in fact, either avoidable (active coping) or not (passive coping). Generally, the active coping instruction produced greater responses to the RIP task than did the passive coping instruction for heart rate, systolic and diastolic blood pressure but not for finger pulse amplitude, thus resembling a beta-adrenergic stimulation. RIP processing rate was not affected, but the response rate (total of hits and commission errors) was greater during active than during passive coping. However, none of these stress reactions differed between abstainers and nonabstainers. On the other hand, both heart rate and the craving to smoke decreased significantly in the abstainer group across the 9 days. Thus, it is concluded that a deprivation of 1 h, 3 or 9 days has no differential effect on physiological stress reactions. PMID- 1924643 TI - Distinguishing between attentional and amnestic effects in information processing: the separate and combined effects of scopolamine and nicotine on verbal free recall. AB - An important issue in our understanding of cholinergic modulation of information processing is the extent to which drug-induced changes affect memory processes per se or simply the attentional processes required for effective acquisition of information. In this study, we examined the separate and combined effects of scopolamine and nicotine on verbal free recall. A single dose of nicotine improved recall performance on supraspan lists (30 words), but not on short lists (10 words). The same dose of nicotine had no effect on the scopolamine-induced recall deficits observed for both 30 and 10 word lists. The results are discussed in terms of the independence of attention and memory processes and the specificity of action of these two cholinergic compounds. PMID- 1924644 TI - Effect of naltrexone on alcohol consumption during chronic alcohol drinking and after a period of imposed abstinence in free-choice drinking rhesus monkeys. AB - Relapse into problematic alcohol drinking is a serious problem in the treatment of alcoholism. Free-choice drinking rhesus monkeys show relapse-like behaviour after imposed abstinence of alcohol, by immediately reinitiating ethanol intake at an increased level. The relapse-like behaviour of the monkeys seems not induced by physical withdrawal, but rather argues for a resistance to extinction of ethanol-reinforced behaviour. It has been suggested that endogenous opioids play a role in the positive reinforcing effect of ethanol. In this study, the effect of the opiate antagonist naltrexone was investigated in eight adult male rhesus monkeys (Macaca mulatta) who had about 1 year experience with alcohol drinking, under two conditions: 1) (expt 1) during continuous and concurrent supply of drinking water and two ethanol/water solutions (16% and 32% (v/v], and 2) (expt 2) after 2 days of alcohol abstinence. In both experiments, each monkey received six doses of naltrexone (0.02, 0.06, 0.17, 0.5, 1.0, 1.5 mg.kg-1); each dose was paired with a placebo injection (im) in a cross-over design. Consumption was measured from 16.00 hours in the afternoon (30 min after injection) to 9.00 hours the next morning. In experiment 1 naltrexone reduced total net ethanol intake in a graded dose-dependent manner. The effect of naltrexone was apparent shortly after injection, and lasted until the following day. Consumption of drinking water was reduced only shortly after injection. In expt 2, reduction of net ethanol intake was largely restricted to the first few hours of reinitiation of alcohol drinking, i.e. the period in which the abstinence-induced increase was manifest. Consumption of drinking water was not affected by naltrexone. Naltrexone hardly influenced consumption of the non-preferred ethanol solution of 32%. It is postulated that the opioid modulation specifically interacted with positively reinforced behaviour. In expt 2 naltrexone reduced ethanol intake at a lower dose (0.17 mg.kg-1) compared to expt 1 (0.50 mg.kg-1), but net ethanol intakes however remained higher. It might be that alcohol abstinence resulted in altered opioid activity, leading to increased ethanol-seeking behaviour. The renewed presentation of ethanol solutions (also) might have stimulated reinitiation of alcohol drinking, representing conditioned incentive stimuli. The reported monkey model of relapse in alcohol drinking could be a useful tool to evaluate new hypotheses and experimental treatments with respect to human alcoholism. PMID- 1924645 TI - Potentiation of the effects of reward-related stimuli by dopaminergic-dependent mechanisms in the nucleus accumbens. AB - Three experiments examined the behavioural, pharmacological and neural specificity of the previously reported potentiation of responding with conditioned reinforcement following intra-accumbens d-amphetamine, by studying the effects of intra-accumbens dopamine (DA) and noradrenaline, using an acquisition of a new response procedure. In experiment 1, the effects of intra cerebral DA infusions (5, 20, 50 micrograms/2 microliters) were compared in four conditions: (i) intra-accumbens DA following positive pairing of the conditioned stimulus (CS) and water during training; (ii) as (i) but also following a systemic dose of the DA receptor antagonist alpha-flupenthixol; (iii) intra accumbens DA following random pairing of the CS and water during training; and (iv) as (i) but with intra-caudate rather than intra-accumbens DA. The results showed that only with intra-accumbens DA in the positive pairing condition was there a significant dose-dependent increase in responding. In experiment 2, the effects of a higher range of doses (20, 100, 200 micrograms) and smaller infusion volume (5, 25, 50 micrograms/l microliters) of intra-accumbens DA were studied, in comparison with a similar range of doses (5, 25, 50 micrograms/l microliters) of intra-accumbens noradrenaline (NA). Only DA produced a selective, dose dependent increase in responding with conditioned reinforcement. In experiment 3 neurotoxic lesions of the dorsal noradrenergic bundle (DNAB) using 6 hydroxydopamine producing profound (about 90%) depletion of cortical and nucleus accumbens NA levels had no effect on the increased responding with conditioned reinforcement produced by intra-accumbens d-amphetamine (3, 10, 30 micrograms/l microliters).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1924646 TI - Acute tolerance to the locomotor stimulant effects of nicotine in the rat. AB - Studies of peripheral nicotinic receptors have revealed that, after an initial agonist action, the receptors remain inhibited either through continued depolarization blockade due to continued presence of the agonist or through a brief inactivation of the receptor following its activation. If a similar phenomenon occurs at central nervous system nicotinic receptors, then behavioral responses to nicotine should exhibit an acute tolerance (tachyphylaxis). Groups of rats were given either saline or 0.2 mg/kg nicotine injections at 20-min intervals in photocell activity cages. A progressive decline in the locomotor responsiveness to nicotine was observed. The time course of this acute tolerance was observed in other rats given initial 0.2 mg/kg nicotine injections followed at differing time intervals by second 0.2 mg/kg nicotine test injections. The secondary antagonism to nicotine's locomotor stimulant effects was maximal at 45 60 min and recovered by 90-120 min. The locomotor response to 0.2 mg/kg nicotine test injections was observed in other rats following exposure to 1.8 mg/kg nicotine, and the behavioral response was attenuated for more than 5 h. PMID- 1924647 TI - What is learned during opiate withdrawal conditioning? Evidence for a cue avoidance model. AB - How conditioned opiate withdrawal gives rise to avoidance behaviour was examined using a defensive burying procedure in rats made dependent with a morphine pellet. The subjects underwent withdrawal precipitated by naloxone (0.1 mg/kg, SC) on two or three occasions in a box containing only a small object. When exposed to the object in the presence of sawdust one or more days later, the subjects avoided contact and buried this object, i.e., pushed and piled the sawdust against it. The behaviour was seen only when withdrawal had been paired with the object, which was the case even with a choice of objects on the test. Approach but no burying was seen in nondependent animals when the object was paired with 1 mg/kg morphine. Burying, therefore, was concluded to be a defensive response elicited in rats by an object specifically paired with precipitated opiate withdrawal. Consideration of burying and other defensive responses reported to be elicited by cues of withdrawal (conditioned place and taste aversion, and suppression), with respect to the behavioural demands of these responses and the test conditions needed to see them, suggested that a goal of avoidance may be a primary event encoded in a withdrawal cue, as is known for predictors of nonpharmacological noxious events (e.g., shock). PMID- 1924648 TI - Distinguishing withdrawal relief and direct effects of smoking. PMID- 1924649 TI - The relationship between pituitary-gonadal function and sexual behavior in healthy aging men. AB - Few studies have assessed the role of pituitary and gonadal hormones on age related changes in sexual behavior in healthy men. We conducted a retrospective and prospective evaluation of sexual function and behavior in 77 healthy married men aged 45 to 74 years. The subjects were studied in the sleep laboratory for four nights with the last night devoted to sequential blood sampling every 20 minutes. Significant age-related decreases in sexual desire, sexual arousal and activity, and increases in erectile problems were noted. Aging was negatively correlated with bioavailable testosterone (bT), was positively correlated with luteinizing hormone (LH), and was not related to total testosterone, estradiol, and prolactin. Bioavailable testosterone, and the ratio of bT over LH showed a close association with several sexual behavior dimensions while total testosterone, estradiol, and prolactin demonstrated few or no behavioral relationships. The age-related effect of bT was, however, a more important determinant of the reported behavioral differences than were the effect of bT independent of age. There was no evidence that changes in circulating hormones contribute to erectile disorders in healthy aging men. PMID- 1924650 TI - The relation between dominance, anger, and hormones in normally aging men: results from the Massachusetts Male Aging Study. AB - This paper examines the relation of two personality characteristics (dominance and anger) to hormones in normally aging men. The relation of the Jackson Personality Research Form E Dominance subscale and the Spielberger Anger Expression scale to serum levels of 17 endocrine variables, including testosterone (T) and dihydrotestosterone (DHT), cortisol, and prolactin, was examined in 1709 men aged 39 to 70 years randomly sampled from the Boston Metropolitan Statistical Area. Canonical correlation analysis resulted in the identification of a personality profile characterized as dominant with some aggressive behavior that tends to correlate with a hormonal pattern labeled the "availability of androgens." These results partially support previous findings in animals, adolescents, and criminal populations that "aggressive dominance" is related to testosterone. PMID- 1924651 TI - Cortisol excretion in high and low cynically hostile men. AB - Cynical hostility as measured by the Cook and Medley Hostility (Ho) Scale has been found in some studies to be associated with increased risk of life threatening illness. Previous laboratory studies of cardiovascular reactivity have been consistent with the general hypothesis that increased physiological responsiveness is one possible mechanism underlying the association between hostility and health. The present study extended this previous research by evaluating urinary cortisol excretion during routine daily activities in a sample of high and low cynically hostile young men. Although high and low Ho groups did not differ in their cortisol excretion upon awakening, the high Ho group displayed more than twice the increase in cortisol excretion during daytime hours as that occurring among low hostile men. This difference dissipated during the evening hours. Results are discussed in terms of possible physiological mechanisms linking hostility and health. PMID- 1924652 TI - Ambulatory blood pressure and heart rate in paramedics: effects of cynical hostility and defensiveness. AB - Ambulatory blood pressure and heart rate responses were obtained in 33 male paramedics during a 24-hour work shift to examine the effects of episodes of occupational stress on cardiovascular reactivity and subjective reports of stress. The aim of this study was to determine how individual differences in cynical hostility and defensiveness interacted with situational demands to affect cardiovascular responses in a natural setting. Defensiveness was found to interact significantly with cynical hostility in predicting subjects' heart rate responses in different work contexts. Specifically, in a hospital setting involving interpersonal conflict, subjects who were high in both defensiveness and hostility showed heart rate responses approximately 10 bpm higher than subjects who were high in hostility but low in defensiveness. The same pattern of relationships was obtained for diastolic blood pressure. High and low hostile subjects were also found to differ from each other in their daily mean levels of ambulatory blood pressure during awake and sleep periods. These findings obtained in a natural setting lend further support to the significance of cynical hostility for cardiovascular reactivity. The results for defensiveness suggest the need for further research on the role of conflicting attitudes in the pathophysiology of cardiovascular diseases. PMID- 1924653 TI - Change in coronary-prone behaviors in the recurrent coronary prevention project. AB - The Recurrent Coronary Preventive Project (RCPP) demonstrated that the addition of Type A counseling to standard cardiac counseling resulted in significant reductions in Type A behavior and in a 44% reduction in reinfarction in post myocardial infarction patients. The purpose of the present study was to describe the specific behavioural and psychosocial changes that occurred during this Type A treatment. Patients undergoing Type A counseling showed significant reductions not only in Type A behavior, but also in the Type A components of hostility, time urgency, and impatience, when compared with patients in the cardiac control group. They also showed significant decreases in depression and anger, and gains in self-efficacy, and marginally significant gains in social support and well being. Type A counseling resulted in a dose-response relationship with most psychosocial outcomes, such that an increasing amount of treatment contacts was associated with increasing change. These data are important in that they specify a range of psychosocial factors that were influenced by treatment. These factors can be considered to be among the possible explanations for the efficacy of the RCPP treatment on the reduction of cardiac recurrences. PMID- 1924654 TI - Cardiovascular reactivity to stress in black male offspring of hypertensive parents. AB - The forearm blood flow (FABF) and other cardiovascular responses of 20 black men with a parental history of hypertension were compared with the responses of 18 black men without a parental history of hypertension. The results showed that sons of hypertensive parents had higher systolic (SBP) and diastolic (DBP) blood pressure than sons of normotensive parents during the initial assessment as well as significantly higher self-determined home SBP. Sons of hypertensive parents had higher SBP responses than sons of normotensive parents during mental challenge and the cold pressor, but there were no group differences in DBP, heart rate (HR), (FABF), or forearm vascular resistance (FAVR) responses to the stressors. Significant positive correlations between HR and FABF responses to the stressors were observed for sons of hypertensive parents. Finally, the results showed that the BP and FAVR responses to the cold pressor (a painful task that elicits alpha-adrenergic activity) were significantly higher than responses to mental challenge (a task that elicits beta-adrenergic activity) for both groups. The implications of these results are discussed in light of current research suggesting that blacks may have a greater tendency toward BP responses mediated by alpha-adrenergic increases in vascular resistance. PMID- 1924655 TI - Plasma catecholamines during behavioral treatments for Raynaud's disease. AB - We have previously demonstrated that the vasospastic attacks of Raynaud's disease can be induced despite blockade of efferent digital nerves and that feedback induced vasodilation is mediated through a non-neural, beta-adrenergic mechanism. Here, we sought to determine the role of sympathetic activity, as measured by plasma epinephrine and norepinephrine, during finger temperature feedback and autogenic training. Thirty-one female patients with idiopathic Raynaud's disease were randomly assigned to receive finger temperature feedback or autogenic training over 28 days. Half of each group began and finished training during the follicular phase of the menstrual cycle, the other half during the luteal phase. During training, significant temperature elevations were shown by feedback patients but not by autogenic patients. There were no significant effects for norepinephrine and epinephrine for either group. Cycle phase did not interact with training effects or with catecholamines. These findings do not support the role of decreased sympathetic activation in behavioral treatments for Raynaud's disease. PMID- 1924656 TI - Intensive versus standard blood glucose awareness training (BGAT) with insulin dependent diabetes: mechanisms and ancillary effects. AB - Insulin-dependent diabetes mellitus (IDDM) patients make critical daily self-care decisions on the basis of what they estimate their blood glucose (BG) levels to be. This study: a) replicated efficacy of Standard Blood Glucose Awareness Training (BGAT), b) evaluated the relative efficacy of an Intensive Blood Glucose Awareness Training (BGAT) to enhance patient accuracy of BG estimation, and c) evaluated the mechanisms and ancillary effects of BGAT. Thirty-nine subjects were randomly assigned to one of three groups. Compared with Control, both Standard and Intensive BGAT improved accuracy (p less than 0.001). Intensive BGAT post treatment accuracy relative to Standard BGAT did not reach statistical significance (p = 0.177). Greater improvement in accuracy was associated with poorer pretreatment accuracy. Only Intensive BGAT improved metabolic control (glycosylated hemoglobin), and this improvement was associated with poorer pretreatment control. The effects of BGAT were highly specific, affecting only accuracy and metabolic control, and not affecting fear of hypoglycemia, diabetes knowledge, of frequency of blood glucose monitoring. PMID- 1924657 TI - Factors related to haloperidol response and dyskinesias in autistic children. AB - A secondary analysis of data pooled from three studies (Anderson et al. 1984, 1989; Campbell et al. 1978) was performed to identify variables predictive of haloperidol response in 125 autistic children, with ages ranging from 2.3 to 8.2 years. Mean behavioral improvement was greater under haloperidol treatment conditions than under placebo. Higher intelligence quotient (IQ) was predictive of reduction in behavioral symptoms under general conditions of haloperidol or placebo treatment, while older children were found to respond favorably to haloperidol itself. Under both haloperidol and placebo conditions, there was also a tendency for greater reduction in symptoms, in terms of raw score and percent change, for those with greater initial severity of illness. Results for initial severity of illness as a predictor of improvement generalized across a wide variety of behavior not specific to autism (e.g., hyperactivity and temper outbursts). However, mean behavioral improvement and its prediction with demographics for individuals tended to be more specific to symptoms related to autism per se. Reduction in symptoms during short-term haloperidol treatment was not found to be related to whether or not children developed dyskinesias in subsequent long-term haloperidol administration. PMID- 1924659 TI - A controlled study of mianserin in moderately to severely depressed outpatients. AB - Following a 1-week, single-blind placebo washout, 150 patients were randomized to double-blind treatment with daily doses of either mianserin, 30 mg to 150 mg; amitriptyline, 60 mg to 300 mg; or placebo, 1 to 5 capsules taken at bedtime (qhs). Mianserin and amitriptyline were found to be comparable in efficacy, and both significantly more effective than placebo in the treatment of major depressive illness. Rating instruments, all of which showed significant improvement in the active drug groups over the placebo, included the 17- and 21 item Hamilton Rating Scale for Depression (HAM-D), Montgomery and Asberg Depression Rating Scale (MADRS), Self-rating Depression Scale (SDS) index, and the Clinical Global Impressions (CGI) Severity of Illness and Improvement rating scales. Furthermore, for most efficacy parameters in the efficacy-evaluable group, the earliest statistically significant difference vs. placebo could be observed at Visit 1 for the mianserin patients and at Visit 3 for the amitriptyline patients. The safety profile for mianserin was comparable with placebo with respect to laboratory values, electrocardiogram changes, vital signs, ophthalmologic evaluations, and most adverse clinical experiences. Complaints of somnolence and weight gain were comparable in the amitriptyline and mianserin groups. Mianserin was superior to amitriptyline in terms of vital signs; anticholinergic effects; and complaints of dizziness, dyspepsia, and tremor. PMID- 1924658 TI - Correlates of antimanic response to valproate. AB - Seventeen patients with acute mania were treated with the antiepileptic agent valproate under placebo-controlled, double-blind conditions for 7 to 21 days. No other psychotropics were allowed, except for lorazepam, up to 4 mg per day, as needed for agitation or insomnia for the first 10 study days only. Of the 17 patients, 12 (71%) showed some response, ranging from a 30 percent to a 100 percent decrease in scores on the Young Mania Rating Scale (MRS). The remaining 5 patients displayed no response to valproate treatment, with increases on the MRS of 3 percent to 13 percent. Compared with nonresponders, responders had an older age of onset and a shorter duration of illness and displayed a higher average serum valproate concentration on Study Days 3 through 6, but not on Study Day 15 or at termination. Degree of valproate response was greater for those patients with more severe sleep disruption at baseline. However, the majority of factors assessed, including a history of rapid cycling and high levels of dysphoria, were not associated with response to valproate. PMID- 1924660 TI - Venlafaxine in depressed outpatients. AB - Venlafaxine is a structurally novel compound with a biochemical and pharmacological profile suggesting antidepressant properties. We report the results of a Phase II, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of venlafaxine in a sample of 93 depressed outpatients. Venlafaxine doses of 25 mg t.i.d., 75 mg t.i.d., and 125 mg t.i.d. were compared to placebo. Patients receiving venlafaxine showed a significantly greater improvement in their mood symptoms compared to those receiving placebo. Venlafaxine was well tolerated and the most common side effect was nausea. There was some evidence to suggest that venlafaxine may have antidepressant activity within the first 2 weeks of treatment. PMID- 1924661 TI - Premenstrual and menstrual symptom clusters and response to calcium treatment. AB - Fourteen perimenstrual symptoms were rated daily by 33 women in a randomized, double-blind, crossover trial of calcium supplementation. Factor analysis was performed on these symptoms using 2,413 daily ratings during the luteal and menstrual phases with at least one symptom present. Four factors (negative affect, water retention, food, and pain) accounting for 67 percent of the total variance were extracted. Internal consistency was high for scales based on these factors. Correlations between the scores ranged from .35 to .69. Scores were low during the intermenstrual phase and much higher during both luteal and menstrual phases. Paired t-tests comparing the intermenstrual phase with both luteal and menstrual phases all resulted in significant differences at p less than .01. There was more pain reported during the menstrual compared with the luteal phase (p less than .01). Calcium supplementation reduced negative affect (p = .045), water retention (p = .003), and pain (p = .036) during the luteal phase and pain (p = .02) during the menstrual phase. PMID- 1924662 TI - Discrepancies between patient report, clinical assessment, and urine analysis in psychiatric patients during inpatient admission. AB - Self-report and clinical assessment of substance use were compared with urine analysis results in 56 male patients consecutively admitted for inpatient psychiatric treatment. All subjects received DSM-III-R Axis I diagnosis and were classified into diagnostic groups. Urine samples were tested for cocaine, marijuana, opiates, phencyclidine (PCP), amphetamines, and barbiturates. Thirty five of the 56 patients (62%) produced urine samples that were positive for at least 1 substance of abuse. Of this group, 15 patients (27% of total sample) denied substance use during the week prior to admission. In addition, the admitting physician did not identify intoxication in 23 of the 35 patients (66%) with positive urines. The admitting physician's assessment matched the patient's answers regarding recent substance use in 79 percent of the patients. This association was especially apparent with the 26 patients who denied recent substance use, all but one of whom received a drug-negative assessment from the admitting physician. PMID- 1924663 TI - Desipramine treatment of alcoholism. AB - Depression has been related to relapsed drinking in alcoholics striving to maintain sobriety. Treatment with tricyclic antidepressants might reverse or prevent depressive symptoms related to relapse, and may reverse biochemical abnormalities hypothesized to underlie both depression and alcoholism, thus helping to prolong abstinence in recovering alcoholics. This is a preliminary report of the findings of an ongoing 6-month, double-blind, placebo-controlled trial of desipramine (DMI) in recently abstinent alcoholics, with stratification on the presence or absence of secondary depression and DMI plasma level monitoring. Hypotheses are that DMI will prolong sobriety and reduce depression secondary to alcoholism significantly more than placebo. Subjects were 34 males and 8 females with 19 subjects stratified as depressed after an average of 16.31 days of sobriety. Depressed DMI subjects were significantly less depressed at the time of their termination from study than depressed placebo subjects. No group differences were found in rate of nonsobriety. However, there was a trend for DMI subjects to maintain sobriety for a longer duration on the study since onset of alcoholism, with 33.3 percent depressed placebo, 9.1 percent nondepressed placebo, 60.0 percent depressed DMI, and 41.7 percent nondepressed DMI subjects having their longest period of sobriety on the study. PMID- 1924665 TI - 30th annual meeting of the New Clinical Drug Evaluation Unit (NCDEU). May 29-June 1, 1990, Key Biscayne, Florida. Posters and free communications. PMID- 1924664 TI - The association of buspirone and its metabolite 1-pyrimidinylpiperazine in the remission of comorbid anxiety with depressive features and alcohol dependency. AB - Recent literature has addressed a frequent comorbidity between alcoholism and anxiety/depression. These disorders have been interdigitated with the brain amines serotonin (5-HT) and norepinephrine. We investigated 51 dually diagnosed patients (generalized anxiety disorder with depressive features plus alcohol abuse/dependency) under a randomized, double-blind, placebo-controlled trial employing the 5-HT1A compound buspirone. Buspirone was superior to placebo as an anxiolytic. It was well tolerated and reduced the number of days patients desired alcohol. At the final study dose, the buspirone metabolite 1 pyrimidinylpiperazine (1-PP) was significantly related to improvement in anxiety, global depressive symptoms, and number of days not using alcohol. Analysis using the Hamilton Rating Scale for Depression and its retardation cluster revealed significant improvement secondary to anxiolysis. Thus, buspirone (especially via its 1-PP metabolite) may be an effective treatment strategy in the anxious or mixed anxious-depressive patient with comorbid alcoholism when other conventional anxiolytics may be contraindicated. PMID- 1924666 TI - Plasma fluphenazine levels and clinical response in newly admitted schizophrenic patients. AB - Seventy-two newly readmitted, drug-free men with the diagnosis of schizophrenia by DSM-III were assigned randomly to receive fluphenazine hydrochloride at 5 mg, 10 mg, or 20 mg daily for 4 weeks. Fluphenazine (FLU), fluphenazine sulfoxide, 7 hydroxyfluphenazine, and fluphenazine N-oxide were measured by highly specific and sensitive radioimmunoassays. Data were analyzed by logistic regression using the Clinical Global Impressions Disabling Side Effects and Global Improvement as the outcome measures. Disabling side effects were defined as "side effects that significantly interfered with patient's functioning" or "side effects that outweigh therapeutic effects" (National Institute of Mental Health 1985, p. 839). Higher plasma FLU levels (up to 4.23 ng/mL) were significantly (p = .015) associated with a higher rate of global improvement. However, close to 90 percent of these acute patients had disabling side effects at a plasma FLU level of 2.7 ng/mL. At least in the patient's view, these disabling side effects negated or compromised the improvement in psychosis. Fluphenazine N-oxide may be a toxic metabolite in that it was more powerfully associated with side effects than was the parent FLU. PMID- 1924667 TI - Predictors of therapeutic response to haloperidol in acute schizophrenia. AB - During a study of neuroleptic threshold haloperidol doses as treatment for newly admitted schizophrenic patients, we examined whether variables extracted from patients' clinical histories, the type and severity of patients' psychopathology at baseline, or the emergence of specific extrapyramidal side effects (EPSE) during treatment were associated with therapeutic response. Rapid therapeutic response was most powerfully predicted by a short (less than 1 month) duration of active illness prior to admission. Severe psychopathology at baseline, or the development of akathisia at neuroleptic threshold doses, portended against early response. More gradual therapeutic response was also associated with limited (less than 6 months) duration of active illness prior to admission. Motor retardation at baseline also characterized late responders. Active illness for more than 6 months prior to admission, greater chronicity of overall course, and heavy nicotine consumption characterized nonresponders. PMID- 1924668 TI - [Parent-child relations as a predisposition for psychogenic pain syndrome in adulthood. A controlled, retrospective study in relation to G. L. Engel's "pain proneness"]. AB - In a retrospective study on 151 chronic pain patients the relevance of childhood factors as described by G. L. Engel ("pain-proneness") are empirically investigated. All patients are studied by a structured interview developed for pain patients. Two groups were clinically differentiated and compared regarding childhood development: A psychogenic pain group (PP) without any somatic pathology (IASP-classification axis 5: 09; n = 75) and a group of chronic pain patients with somatic pathology (OP; n = 35). A "psychosomatic group" (IASP-axis 5: 07, e.g. migraine; n = 41) was excluded from further investigation. There are significant differences between PP and OP regarding the emotional quality of the relationship to both parents, physical abuse by the parents, a higher strain of both parents by the job (often a family enterprise), frequent aggressive conflicts between parents and their separation or divorce. Often a favorite toy or animal replaced the missing object. Pain or complaints with same localisation of significant others are significantly more frequent. No significant differences between the two pain groups are found as to loss of parent by death and the number of hospitalisation during childhood. PMID- 1924669 TI - [The concept of integrated internal medicine-psychosomatic patient management- experiences and results with its application in a general hospital]. AB - Psychosomatic therapy has been realized by integration into general ward's therapeutic program in a general hospital. Within 3 1/2 years of development the medical staff has been qualified to perform basic elements of psychosomatic therapy, whilst the structure of the medical department has been changed in different aspects. During a period of 28 days the real extend of psychosomatic therapy now has been evaluated by questionnaire: 438 psychosomatic and psychosocial interventions were documented in this time, concerning 149 patients (= 53% of all patients treated in the department). Causes, trigger mechanic, settings, frequency, median duration, and different kinds of all these interventions are described. According to the clientele of our medical department, with a lot of elderly and multi-handicapped persons, the main topics of interventions concerned--besides of specific psychosomatic treatment- addiction and problems of alcoholism, coping strategies and compliance, as well as further support of handicapped singles after discharge. PMID- 1924670 TI - [Psychobiology of grief and loss processing--recent immunologic and endocrinologic approaches and findings]. AB - Recent studies demonstrate the importance of social relationships for maintaining health. As mechanisms remain hidden in ongoing relationships, much of our knowledge comes from the deleterious health consequences of loss or separation. Despite the central importance of object loss in psychosomatic models of disease, physiological links have hardly been explored. After a short review of psychological processes of mourning, recent psychoimmunological and endocrinological studies are discussed. These show fairly consistent immunosuppressive effects of depressive disorders and of impending and actual loss of the partner and endocrinological changes, also related in magnitude to depression. First results of intervention studies show favorable endocrinological and immunological changes presumably due to promotion of social relations and reduction of distress. Despite manifold methodological problems this approach provides a promising access towards understanding the meaning of social relations for physiological regulation. Decisive issues of the relationship of immunological and endocrinological changes and their clinical relevance must await further longitudinal studies which should include a more detailed psychological analysis of mourning and object relations. PMID- 1924671 TI - [Variation of response structures in relation to degree of personal involvement- a methodologic study exemplified by the "Discrimination Devaluation Scale"]. AB - When comparing results from different populations there is an underlying assumption that the response patterns elicited by the instrument used are stabile across the study groups. But it remains an open question whether this assumption is correct or not--especially in the case when the populations are involved to a different degree into the problem which is the object of the investigation. In fact, we are able to show that the dimensional structure of an instrument developed for the evaluation of stigma psychiatric patients are exposed to, varies depending on the degree of personal involvement with psychiatric disorder. This leads us to the conclusion that a quantitative comparison of parameters appears not warranted as long as the dimensional stability of the instrument over the various populations has not been shown. PMID- 1924672 TI - [Psychodynamically oriented inpatient treatment of psychotic patients--a contribution to psychotherapy continuing education in clinical psychiatry]. AB - Chances and problems of integrating a psychodynamic model of psychosis in psychiatry are pointed out by means of case studies and experiences in supervising psychiatric teams. The analysis of the interpersonal and institutional mechanisms of defence and the acting communication in the doctor patient-relationship takes a central position in a therapeutic concept. Psychotherapeutical training of psychiatrists is confronted with the unconscious material that psychiatric institutions consist of. Focussing on this institutional tension field in supervision contributes to the development of a context-related psychotherapeutical attitude in the clinical psychiatrist. This prevents collusive patterns of relationship and enables us to establish necessary modifications of treatment. PMID- 1924673 TI - Aortic dissection. PMID- 1924674 TI - Diagnostic delay and outcome in surgery for type A aortic dissection. AB - Twenty-two patients with acute type A aortic dissection presented to this hospital over a three-year period. The initial diagnosis was incorrect in 12 (54.5 per cent) and in 11 of these the error occurred in peripheral hospitals before referral. This diagnostic mistake lead to a delay in surgical treatment of 2-9 days (median 5 days). Three deaths occurred without surgery, and two of these could have been considered for repair if the correct diagnosis had been made earlier. In the surgically treated group, a 30-day survival of 16 out of 19 (84.2 per cent) was achieved and the three deaths were all related to late referral. Two died because of bowel infarction and one because of respiratory failure. An increased general awareness of acute aortic dissection is necessary as early diagnosis, before the onset of irreversible ischaemic events, allows a high surgical success rate. PMID- 1924675 TI - Antibodies to cardiolipin in stroke: association with mortality and functional recovery in patients without systemic lupus erythematosus. AB - Antibodies to cardiolipin were measured in 100 consecutive patients with first ever stroke, on admission and at three and six months after the acute event. One hundred healthy, age- and sex-matched, British elderly individuals were also screened for antibodies to cardiolipin as a control group. Elevated levels of anticardiolipin antibody (i.e. 5 SD above the laboratory control mean) were present in none of the control group, but in 21 per cent of the patients with stroke. Thirteen of these 21 patients (62 per cent) died within three months, compared to 17 (21.5 per cent) of the seventy-nine patients without elevated levels of anticardiolipin antibodies (p less than 0.001). Six of the eight survivors with persistently elevated anticardiolipin antibodies had significant residual disability following stroke (Barthel score 0-9) compared to 11 of the 62 without (p less than 0.001). Two patients with initially raised anticardiolipin antibodies who became independent at six months showed a progressive decline in the level of these antibodies to normal. The presence of high levels of anticardiolipin antibody did not correlate with other recognized prognostic indices of stroke, except for incontinence. No correlation was noted between levels of antibody to cardiolipin, antinuclear factor, antibody to double stranded DNA and C-reactive protein, either in the stroke patients or in the elderly control population. Hypertension was significantly more common in the patients with high anticardiolipin antibodies than in the rest of the patients in the stroke population (p = 0.33). There was no correlation between levels of anticardiolipin antibody and age. Anticardiolipin antibody may be considered as an independent prognostic marker for both mortality and clinical outcome after acute stroke. PMID- 1924676 TI - Aluminium mobilization following renal transplantation and the possible effect on susceptibility to bacterial sepsis. AB - We monitored urinary aluminium excretion in 60 renal allograft recipients for the first 6 months following transplantation. Plasma and urinary aluminium values steadily decreased during the study period. Patients who suffered two or more bacterial infections during this period excreted more urinary aluminium than those with only one or no infections. Twenty patients experienced a two-fold or greater sudden unexpected increase in urinary aluminium excretion: 14 of these patients (60 per cent) had evidence of infection (10 bacterial and four viral), at this time. Both urinary aluminium and fractional aluminium excretion were greater in the 10 patients with bacterial infection than in the other 10 patients. Thus, patients who suffered bacterial infections had higher base-line urinary aluminium excretion, suggesting a higher body burden of aluminium. In addition, bacterial sepsis was associated with aluminium release from tissue stores with an associated increase in urinary aluminium excretion. This implies that patients with an increased body burden of aluminium are more prone to bacterial sepsis, and that aluminium excretion is increased during sepsis. PMID- 1924677 TI - Intracranial and cerebral perfusion pressure changes before, during and immediately after orthotopic liver transplantation for fulminant hepatic failure. AB - Several centres that perform liver transplantation for fulminant hepatic failure have experience of patients who have not regained consciousness despite adequate graft function. In some of these, decerebration because of elevation in intracranial pressure was thought to have occurred intraoperatively or in the early post-operative period. In the present study six patients with fulminant hepatic failure who were transplanted had extradural monitors inserted before operation. Intracranial pressure had been controlled prior to transplantation and rose during the pre-clamp phase of the operation. Levels fell during the anhepatic phase but rose again during the reperfusion phase (p = 0.033). Overall, from the induction of anaesthesia to the reperfusion phase there was a significant increase in mean intracranial pressure (p less than 0.01). The cerebral perfusion pressure fell after induction of anaesthesia from a median 54 mmHg (range 46-62) to a median 35 mmHg (range 19-49, p less than 0.001) in the pre-clamp phase and remained low throughout the operation. During the first 10 hours after transplantation, three patients had further episodes of intracranial hypertension requiring treatment and it is important that monitoring should be continued through this period. PMID- 1924678 TI - A pre-eclamptic-like syndrome associated with hypothyroidism during pregnancy. AB - Hypothyroidism presenting during pregnancy is rare, probably due to the lower incidence of hypothyroidism during the reproductive years, and because myxoedema causes anovulatory cycles. We report an unusual case of hypothyroidism during a 34-year-old woman's fifth pregnancy, complicated by hypertension, oedema, pericardial effusion and severe nephrotic syndrome. This is the first report of renal biopsy abnormalities under these circumstances. Review of the literature regarding hypothyroidism presenting during pregnancy leads us to suggest that hypothyroidism during pregnancy may mimic pre-eclampsia. PMID- 1924679 TI - Proximal cutaneous necrosis associated with small vessel calcification in renal failure. AB - Cutaneous necrosis with microvascular calcification is a rare and serious complication of chronic renal failure and has been given the sobriquet of 'calciphylaxis'. We describe four dialysis-dependent patients with proximal cutaneous necrosis who presented with this distinctive clinical syndrome. All of the patients were women aged between 40 and 68, and all developed widespread livedo reticularis followed by painful subcutaneous nodules which progressed to eschar-like lesions of the skin. Microvascular calcification was seen on radiographs of the limbs, especially at the sites of the cutaneous lesions. Serum phosphorus concentrations were increased in all the patients (maximally to between 2 and 3.6 mmol/l), but serum calcium concentrations were mildly increased in only two patients and only one patient had hyperparathyroidism. Histological examinations of skin biopsies in two patients showed cutaneous infarcts. Three patients died despite a reduction in serum phosphorus concentration and one patient improved. The proximal form of 'calciphylaxis' constitutes a distinct syndrome which can be recognized clinically. PMID- 1924680 TI - The clinical entity of orofacial Crohn's disease. AB - The clinical features, treatment and outcome of 29 patients with oral Crohn's disease seen over a 6-year period have been reviewed. Findings on clinical examination included labial swelling (19 patients), buccal mucosal cobblestoning (11), linear ulceration (11), lumps (five), and mucosal tags (two). Eleven patients had multiple features. Eight patients developed symptoms within the first decade of life and nine patients had symptoms for more than 4 years before diagnosis; the mean age at diagnosis was 30 (range 6-78) years. Fourteen of these patients (48 per cent) have Crohn's disease elsewhere in the alimentary tract, and in nine patients the oral disease predated the development or detection of Crohn's disease at other sites. Eight patients (25 per cent) have required no specific therapy for their oral disease and 12 have been treated with systemic corticosteroids of whom three are steroid-dependent. No other pharmacological approach to treatment has been successful and elimination diets, tried by five patients, had no effect. Oral Crohn's disease has a characteristic naked-eye appearance, may be the first or only manifestation of Crohn's disease and usually improves with oral corticosteroid treatment. PMID- 1924681 TI - Microscopic behaviour of DNA during electrophoresis: electrophoretic orientation. PMID- 1924682 TI - Biophysical processes in invertebrate photoreceptors: recent progress and a critical overview based on Limulus photoreceptors. AB - Limulus ventral nerve photoreceptor, a classical preparation for the study the phototransduction in invertebrate eyes, seems to have a very complex mechanism to transform light energy into a physiological signal. Although the main function of the photoreceptor is to change the membrane conductance according to the illumination, the cell has voltage-activated conductances as well. The voltage gated conductances are matched to the light-activated ones in the sense that they make the function of the cell more efficient. The complex mechanism of phototransduction and the presence of four different voltage-gated conductance in Limulus ventral nerve photoreceptors indicate that these cells are far less differentiated than the photoreceptor cells of vertebrates. Indications accumulated in recent years support the view that the ventral photoreceptor of Limulus has different light-activated macroscopic current components, ion channels and terminal transmitters. After conclusions from macroscopic current measurements (Payne, 1986; Payne et al. 1986 a, b), direct evidence was presented by single-channel (Nagy & Stieve, 1990 a, b; Nagy, 1990 a, b) and macroscopic current measurements (Deckert et al. 1991 a, b) for three different light activated conductances. It has been shown that two of these conductances are stimulated by two different excitation mechanisms. The two mechanisms, having different kinetics, release probably two different transmitters. One of them might be the cGMP (Johnson et al. 1986), the other one the calcium ion (Payne et al. 1986 a, b). However, the biochemical processes which link the rhodopsin molecules and the ion channels are not known. The unknown chemical details of the phototransduction result in a delay for the mathematical description of the biophysical mechanisms. More biochemical details are known about the adaptation mechanism. It was found that inositol 1,4,5-trisphosphate is a messenger for the release of calcium ions from the intracellular stores and that calcium ions are the messengers for adaptation (Payne et al. 1986 b; Payne & Fein, 1987). Concerning the mechanism of calcium release, it was revealed that a negative feedback acts on the enzyme cascade to regulate the internal calcium level and to protect the stores against complete emptying (Payne et al. 1988, 1990). Calcium ions also play an important role in the excitation mechanism. (a) In [Ca2+]i depleted cells the light-induced current was increased after intracellular Ca2+ injection, suggesting that calcium is necessary for the transduction mechanism (Bolsover & Brown, 1985).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1924683 TI - Informed consent, AIDS, and the practicing dentist. PMID- 1924684 TI - The obituary for amalgam. PMID- 1924685 TI - The dental amalgam controversy. PMID- 1924686 TI - Living with amalgam: an environmental perspective. PMID- 1924688 TI - Reproducibility of occlusal contacts utilizing a computerized instrument. AB - This study was designed to examine clinically the accuracy and reproducibility of occlusal contacts made by a computerized device (the T-scan) in ten asymptomatic subjects. The results showed 100% accuracy and reproducibility for all contacts in all subjects. A great advantage of this instrument over silk marking ribbon is that it not only records contacts but can also analyze the timing and force of each contact. PMID- 1924687 TI - Enamel remineralization: how to explain it to patients. AB - The term remineralization of initial enamel caries is frequently used, but mainly at research conferences and in lecture rooms. Clinicians avoid discussing remineralization and white-spot enamel lesion formation with patients because details of the processes are complex. Patients, therefore, incorrectly assume that cavitation occurs right at the onset of caries and that a restoration must be placed to halt further progression of the lesion. Although laboratory and clinical studies have shown that initial white-spot enamel lesions can remineralize, patients have little or no access to this information. The schematic diagrams in this paper explain the diffusion of organic acids from plaque between enamel crystals, the partial loss of mineral from enamel crystals, and subsequent demineralization and remineralization that produces the white-spot lesion. Further, these diagrams may help clinicians explain remineralization as simply as possible to patients who present with white-spot enamel lesions. PMID- 1924689 TI - Multiple therapy approach to juvenile periodontitis: a case report. AB - Various therapeutic techniques for the treatment of juvenile periodontitis are reported in the literature, with occasional contradictory results. One of the reasons for the contradictory results may be differences in patient selection and/or response to treatment. The following report describes the results of various treatment modalities, in different sites in the same individual, on localized juvenile periodontitis. PMID- 1924690 TI - Optimal citric acid concentration for dentinal demineralization. AB - A number of acids have been shown to have a peak concentration above which the rate of enamel demineralization diminishes. Citric acid, used to demineralize dentin in periodontal regenerative procedures, is one such acid. The purpose of this study was to ascertain if there were an optimal concentration of citric acid with which to demineralize dentin. Various concentrations of citric acid were applied to bovine dentin and then examined with atomic absorption spectrophotometry to measure the amount of calcium dissolved in each concentration. The ppm calcium/% citric acid solution rose from 0.38 +/- 0.38 ppm/0% (control) to a peak of 7.54 +/- 2.26 ppm/24%, then fell to 2.43 +/- 0.59 ppm/80%, suggesting that there may be a peak concentration beyond which effective dentinal demineralization diminishes. The peak solution was pH = 1.42. PMID- 1924691 TI - Staining of resin-based veneering materials with coffee and tea. AB - Two light-activated, and three heat-polymerized, resin-based veneering materials were exposed to boiled coffee, filtered coffee, or tea at 50 degrees C and evaluated for color stability. Specimens immersed in distilled water in the dark at 37 degrees C for 4 months were also assessed. One of the light-activated, resin-based veneering materials underwent intrinsic discoloration during the long term immersion both in distilled water and in the staining solutions. The discoloration of the other materials by tea was mainly due to surface adsorption of the colorants. Discoloration by coffee was due to adsorption, and also to absorption of colorants by two of the materials investigated. This absorption and penetration of colorants into the organic phase of the veneering materials were probably due to compatibility of the polymer phase with the yellow colorants of coffee. PMID- 1924692 TI - Microleakage of three dentinal bonding systems: a 6-month evaluation. AB - This study evaluated the marginal sealing ability of three of the latest generation of dentinal bonding agents following 6 months of storage in a 37 degree C water bath. Class V preparations were placed at the cementoenamel junction of extracted human molars. Herculite XR was used to restore cavities that had been pretreated with Gluma, Tenure, or XR Bond. The restored teeth were thermally stressed every 30 days during the following 6 months, and then microleakage was assessed by dye penetration. Under the experimental conditions, the microleakage associated with XR Bond and Gluma was not statistically significantly different. XR Bond performed statistically significantly better than Tenure (a = 0.01). PMID- 1924694 TI - Restoration of a cracked tooth with a bonded amalgam. AB - The diagnosis and treatment of the cracked tooth can present difficulties. The causes of the cracked tooth include masticatory accident, radical preparation and overuse of direct restorative materials, trauma from occlusion, and torque on abutment teeth. Placement of a cast restoration covering the cusp is usually suggested. However, bonded restorations are effective in restoring the strength of teeth weakened by cavity preparation. A material that bonds amalgam to dentin may present a more conservative and less expensive restoration of the cracked tooth. PMID- 1924693 TI - Bond strength evaluation of a Class V composite resin restoration. AB - A three-dimensional cavity design was used to test the bond strength between restorative materials and tooth structure. Results indicated that bonding agents that rely on mechanical retention to the dentinal smear layer produced relatively low bond strengths. Bonding agents that require smear layer modification yielded mixed results, possibly because of differences in chemical formulation. The three dimensional cavity design employed in this study is a replicable one, allowing the creation of standardized, clinically relevant preparations. PMID- 1924695 TI - Functional and esthetic rehabilitation of an adolescent cleft lip and palate patient. AB - Many patients with clefts that also affect the alveolar ridge present with congenital absence of the permanent maxillary lateral incisors. This paper describes the treatment of an adolescent cleft lip and palate patient whose missing and unesthetic maxillary incisors were replaced by a combination of fixed and removable partial dentures. PMID- 1924696 TI - Voltaire, medicine, and dentistry. AB - Voltaire, the leading French intellect of the 18th century, was a notorious hypochondriac. His numerous letters contain hundreds of references to his medical and dental disorders, as well as to those of close friends. Voltaire lived to be 84 years old, but not without suffering from several systemic medical disorders and from periodontal disease that left him nearly edentulous by his mid-50s. His dental condition was diagnosed as a scorbutic condition, requiring systemic medication. As a result of neglect and possible mercury intoxication, his condition worsened, and he lost most of his teeth and suffered facial collapse because he did not wear a dental prosthesis. This paper recounts events in Voltaire's life that were connected to his medical and dental history, and in so doing provides a glance at medical and dental practice in 18th-century France. PMID- 1924697 TI - Animal models of radiation carcinogenesis and developments in molecular biology. PMID- 1924698 TI - Biophysical factors influencing radiation carcinogenesis in cultured cells and animals. PMID- 1924699 TI - Animal models in radiation carcinogenesis--biophysical considerations. PMID- 1924700 TI - In vitro transformation systems in experimental carcinogenesis: towards an integrated approach. PMID- 1924701 TI - Chromosomal changes: radiation sensitive sites on chromosome 2 and their role in radiation myeloid leukaemogenesis in the mouse. PMID- 1924702 TI - The use of transgenic mice in unraveling the multistep process of tumorigenesis. AB - The development of cancer has long been perceived to be a complex and multistep process in which a normal cell progresses to a fully malignant tumor cell in a step-by-step fashion. At the molecular level it is believed that these steps correspond to the acquisition of activated oncogenes or alternatively the inactivation of tumor suppressor genes. With the ability to stably transfer foreign genetic information into the germ line of animals a new powerful tool to study oncogenes became available. PMID- 1924703 TI - ras proteins and the ras-related signal transduction pathway. AB - Mammalian ras genes may naturally acquire oncogenic transformation potential through some point mutations which result in the impairment of the normal ras protein functions, and which are localised in codons 12, 13 or 61. Mutationally activated ras alleles were found in a wide variety of human and carcinogen (including radiation)-induced animal malignancies. In man, myeloid leukemias are often associated with the presence of a mutationally activated ras gene (for review, see Bos JL (1989), Cancer Res 49:4682-4689). However, we failed till now in our attempts to detect oncogenic ras mutations in radiation-induced mouse myeloid leukemias. We thus have the feeling that ras might perhaps participate to tumorigenesis through another mechanism provoking a deregulation of the ras protein functions. In order to help evaluate such a possibility, we give here a very concise overview of the properties of the ras proteins and of their regulation by a variety of still hypothetical molecular switches. This overview does not include bibliographic references. Indeed, we gathered much of the information described below at the Cold Spring Harbor Symposium on "Function and Evolution of ras Proteins", May 9-13, 1990. Communications presented at Cold Spring Harbor Symposia may contain preliminary data and should not be cited in bibliographies. Another voluntary omission in this overview is that, for the sake of simplicity, we do not mention whether the data were obtained from experiments performed on H-, K- or N-ras. Details can be found in the published book of abstracts. PMID- 1924704 TI - Growth factor and growth factor receptor in radiation carcinogenesis. PMID- 1924705 TI - Multigeneration carcinogenesis. PMID- 1924706 TI - Age-dependence of susceptibility to carcinogenesis by ionizing radiation in mice. PMID- 1924707 TI - Experimental studies of radiation-induced leukaemia. PMID- 1924709 TI - Induction of mammary tumors by ionising radiation. PMID- 1924708 TI - Acute myeloid leukemia induction in CBA/H mice by irradiation with fission neutrons as a function of exposure rate. PMID- 1924710 TI - Quantitative and molecular comparison of initiation frequency of mammary carcinogenesis by radiation and chemical carcinogens. PMID- 1924712 TI - When are animal experiments necessary? Factors of significance to the development of radiogenic bone tumors. PMID- 1924711 TI - Bone tumor induction after incorporation of short-lived radionuclides. AB - Temporally-limited internal irradiation after incorporation of short-lived bone seeking radionuclides is a useful experimental tool for the investigation of extrinsic and intrinsic factors which modify the dose dependence of bone tumor risk. Here we describe some of the results obtained in experiments with female mice (mainly NMRI). The future aim of such experiments should be the prediction of risk of late effects using early molecular-biological changes. Molecular biological descriptions in our model are at present very limited. PMID- 1924714 TI - The role of animal models in radiation lung carcinogenesis. PMID- 1924713 TI - Lung cancer in laboratory animals. PMID- 1924715 TI - Radiation carcinogenesis in large animals. PMID- 1924716 TI - Analysis of animal carcinogenesis data by various mathematical methods. PMID- 1924717 TI - Mathematical methods in the analysis of animal experiments. PMID- 1924718 TI - Measurement of three-dimensional radiation dose distributions using MRI. AB - Recent investigations have shown that nuclear magnetic resonance (NMR) can be used in conjunction with a suitable chemical dosimeter to estimate the dose from ionizing radiation (Gore et al., Phys Med. Biol. 29, 1189-1197, 1984). Based on this fact it was proposed that spatial dose distributions can be measured in gels infused with the chemical dosimeter using NMR imaging. There have been few such attempts and they provided only qualitative results. In this paper, we report results demonstrating the feasibility of obtaining quantitative dose distribution measurements by this technique. It is shown that quantitative dose distribution measurements necessitate the calculation of relaxation rate maps. We have determined that the spin-spin relaxation rate is a more sensitive parameter than the spin-lattice relaxation rate. It is also demonstrated that the addition of chemical sensitizers could improve the dose sensitivity of the measured NMR parameters. The two features characterizing a photon beam, depth-dose relationship, and beam profile as measured by this technique are in good agreement with the measurements using conventional methods, ionization chambers, and film dosimetry. PMID- 1924719 TI - Quinolone therapy in the prevention of mortality after irradiation. AB - The effect of oral therapy with three quinolones (ofloxacin, ciprofloxacin, and pefloxacin) in the prevention of postirradiation bacteremia and mortality was tested in B6D2F1 mice given 9.5 Gy 60Co gamma radiation. Only 8 of 60 (13%) untreated mice survived for 30 days, compared to 47 of 60 (78%) mice treated with ofloxacin, 44 of 60 (74%) mice treated with ciprofloxacin, and 42 of 60 (70%) mice treated with pefloxacin (P less than 0.05). The organisms recovered from the mice were Streptococcus spp. and Enterobacteriaceae. More Enterobacteriaceae were recovered from the livers of untreated animals than from the mice treated with the quinolones. However, no reduction in the number of Streptococcus spp. was noted in the animals given quinolones when compared to controls. This study shows that quinolones prolonged survival and decreased systemic spread of Enterobacteriaceae up to 30 days after exposure of mice to lethal irradiation. PMID- 1924720 TI - Maintenance of intracellular free Ca2+ homeostasis following lethal heat shock. AB - We have manipulated the extracellular Ca2+ concentration (1.8 mM in normal Dulbecco's modified Eagle's medium) to test whether the resulting effect on intracellular free Ca2+ homeostasis was similar in heat-sterilized and nonheated mouse NIH-3T3 cells. The responsiveness of the intracellular free Ca2+ concentration to changes in the extracellular Ca2+ concentration was not affected by prior treatment of the cells with trypsin, or by the extracellular Ca2+ concentration during dye loading (indo-1, AM). Rather, the intracellular free Ca2+ concentration was dependent upon the ambient Ca2+ concentration during analysis by flow cytometry. When the extracellular Ca2+ concentration was decreased to 0.017 mM, either before or after a lethal heat shock, the intracellular free Ca2+ concentration (approximately 300 nM) decreased to a similar extent in both heated and control cells (to approximately 30-100 nM). Similarly, when the extracellular Ca2+ concentration was increased to 15.0 mM, either before or after a lethal heat shock, the intracellular free Ca2+ concentration exhibited a quantitatively similar increase in both heated and nonheated cells (to approximately 400-1000 nM). These data indicate that a lethal heat dose does not inhibit the intact cell's ability to maintain intracellular free Ca2+ homeostasis. PMID- 1924721 TI - An appraisal of the value of the contaminated Poisson method to estimate the dose inhomogeneity in simulated partial-body exposure. AB - The situation in which inhomogeneous radiation exposure is likely to occur with accidental overexposure was simulated by studying chromosome aberrations in mixtures of male irradiated and female nonirradiated lymphocytes. The data were evaluated by means of the contaminated Poisson method. For X-ray doses from 1 to 10 Gy and ratios of irradiated to nonirradiated blood from 1:1 to 1:19, a good agreement was found between calculated and applied radiation doses and fractions exposed. PMID- 1924722 TI - The calculation of the mean inactivation dose by approximated methods. PMID- 1924723 TI - Point mutations and radiation carcinogenesis. PMID- 1924724 TI - Effects of procaine on the intracellular pH of Chinese hamster ovary cells heated at 42.0 or 45.0 degrees C. AB - The local anesthetic procaine greatly sensitizes cells to hyperthermia. Though it is generally accepted that procaine is a membrane-active agent that increases membrane fluidity in cells, the mechanism by which it potentiates heat killing is unknown. In this paper we report changes in intracellular pH (pHi) of Chinese hamster ovary (CHO) cells heated at 42.0 or 45.0 degrees C in the presence of procaine. The pHi was measured with flow cytometry using the dye 1,4-diacetoxy 2,3-dicyanobenzene (ADB). Studies were carried out using cells grown at normal pH (7.3) or cells placed in low-pH (6.6) medium 4 h prior to and during heating (acute low-pH treatment). Low-pH-adapted cells (PHV2), which were obtained previously by continuous culture in pH 6.6 medium, were also used. Normal cells heated in the presence of procaine at pH 7.3 underwent a large decrease in pHi compared to cells heated without procaine. Procaine had little additional effect on the intracellular pH of cells in medium with a pH of 6.6 for 4 h before and during 30 min of heating. PHV2 cells exposed to chronic low-pH conditions were resistant to acidification when heated with or without procaine. The surviving fraction of cells heated with procaine was significantly lower under all pH conditions than that of cells heated without procaine. Cells heated at 42.0 degrees C with procaine also became greatly acidified and their survival was reduced. These data suggest that the reduction in pHi caused by procaine may be part of the mechanism of heat sensitization, but cannot account for it entirely. Furthermore, the degree of procaine sensitization and intracellular acidification is dependent on the extracellular pH, with a larger effect occurring at pH 7.3 than at pH 6.6. PMID- 1924725 TI - DNA lesions that signal the induction of radioresistance and DNA repair in yeast. AB - DNA recombinational repair, and an increase in its capacity induced by DNA damage, is believed to be the major mechanism that confers resistance to killing by ionizing radiation in yeast. We have examined the nature of the DNA lesions generated by ionizing radiation that induce this mechanism, using two different end points: resistance to cell killing and ability of the error-free recombinational repair system to compete for other DNA lesions and thereby suppress chemical mutation. Under the various conditions examined in this study, the "maximum" inducible radiation resistance was increased approximately 1.5- to 3-fold and suppression of mutation about 10-fold. DNA lesions produced by low-LET gamma rays at doses greater than about 20 Gy given in oxygen were shown to be more efficient, per unit dose, at inducing radioresistance to killing than were lesions produced by neutrons (high-LET radiation). This suggests that DNA single strand breaks are more important lesions in the induction of radioresistance than DNA double-strand breaks. Oxygen-modified lesions produced by gamma rays (low-LET radiation) were particularly efficient as induction signals. DNA damage due to hydroxyl radicals (OH.) derived from the radiolytic decomposition of H2O produced lesions that strongly induced this DNA repair mechanism. Similarly, OH. derived from aqueous electrons (e-aq) in the presence of N2O also efficiently induced the response. Cells induced to radioresistance to killing with high-LET radiation did not suppress N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-generated mutations as well as cells induced with low-LET radiation, supporting the conclusion that the type of DNA damage produced by low-LET radiation is a better inducer of recombinational repair. Surprisingly, however, cells induced with gamma radiation in the presence of N2O that became radioresistant to killing were unable to suppress MNNG mutations. This result indicates that OH. generated via e-aq (in N2O) may produce unusual DNA lesions which retard normal repair and render the system unavailable to compete for MNNG-generated lesions. We suggest that the repairability of these unique lesions is restricted by either their chemical nature or topological accessibility. Attempted repair of these lesions has lethal consequences and accounts for N2O radiosensitization of repair-competent but not incompetent cells. We conclude that induction of radioresistance in yeast by ionizing radiation responds variably to different DNA lesions, and these affect the availability of the induced recombinational repair system to deal with subsequent damage. PMID- 1924726 TI - Epithelial cell proliferation and uptake of radiolabeled urogastrone in the intestinal tissues following abdominal irradiation in the mouse. AB - We have evaluated the rate of crypt cell production and uptake of radiolabeled recombinant human urogastrone (125I-rhUG) in the intestinal tissues of the mouse at 3, 5, 7, 9, and 12 days following irradiation of the abdomen with 9 Gy. At autopsy, the animals were injected intraperitoneally with 1 microgram/g body weight of the metaphase arrest agent, vincristine sulfate, and 25 muCi of 125I rhUG (specific activity 1.7 muCi/micrograms) to quantify the rate of crypt cell production and uptake of radiolabeled urogastrone, respectively. The results indicated that the rate of crypt cell production was increased significantly in the irradiated animals compared to the unirradiated animals and showed a peak on the 3rd and 5th postirradiation days in small intestine and colon, respectively. The uptake of 125I-rhUG was increased significantly on the 3rd postirradiation day in the intestinal tissues but showed a bimodal pattern with peaks on the 3rd and 9th postirradiation days. These results suggest that there may be a close association between epithelial cell proliferation and uptake of 125I-rhUG, particularly in the early part of recovery of intestinal mucosa following irradiation. However, these data do not discriminate whether the increased uptake of 125I-rhUG is the cause or the effect of proliferation induced by an irradiation stimulus. Further analysis also revealed that there was no relationship between crypt depth and 125I-rhUG uptake. However, crypt depth was inversely correlated with villus height in the proximal small intestine but not in the ileum. Villus height was correlated inversely with 125I-rhUG uptake in the ileum and jejunum but not the duodenum. The rate of crypt cell production was strongly correlated with crypt depth throughout the intestine and inversely correlated with villus height. This suggests that villus-to-crypt inhibitory feedback may be a primary regulator of cellular proliferation in the crypts and the association of 125I-rhUG uptake with proliferation indirectly reflects this interaction. PMID- 1924727 TI - Radiation protection and restoration by the synthetic 163-171 nonapeptide of human interleukin 1 beta. AB - We have previously reported that the synthetic nonapeptide VQGEESNDK, position 163-171 of human interleukin 1 (IL-1 beta), when injected in immunodepressed mice, shows immunorestorative activity similar to that of the whole protein, but with no IL-1-like inflammatory effects [Frasca et al., J. Immunol. 141, 2651-2655 (1988)]. In the present study we have compared the protective and restorative activities of the nonapeptide and human recombinant (hur) IL-1 beta on the survival of lethally irradiated mice. When mice were given a single injection of different doses of the nonapeptide or hurIL-1 beta 20 h before total-body irradiation, both molecules increased the percentage survival of mice exposed to 750 or 850 cGy, but not to 950 cGy. The nonapeptide, however, is less effective than hurIL-1 beta and displays a different dose-response relationship, suggesting that the two molecules act through different radioprotective pathways. When mice were injected with the nonapeptide or hurIL-1 beta immediately after exposure to 850 cGy, the percentage survival was also increased but restoration was lower than protection in both cases. The nonapeptide was also less effective than hurIL 1 beta in restoration, but the two molecules displayed a comparable dose-response relationship as if they shared similar mechanisms. These findings indicate that the 163-171 nonapeptide is able to protect from lethal radiation injury and to restore viability. The nonapeptide appears less effective than hurIL-1 beta but does not exhibit the IL-1-like side effects of the whole molecule. PMID- 1924728 TI - Paternally inherited effects of gamma radiation on mouse preimplantation development detected by the chimera assay. AB - It has previously been shown that type B spermatogonia in male mice treated with 0.05 Gy of X rays undergo an alteration expressed by progeny embryos as a cellular proliferation disadvantage in a chimera assay. We wished to obtain information on the assay's detection limit to ionizing radiation and on the radiosensitive target in male germ cells. Male mice were briefly irradiated with 137Cs gamma rays at nominal absorbed doses of 0.0, 0.0015, 0.005, 0.010, or 0.05 Gy and then mated for the next 8 weeks to untreated females. Four-cell embryos from treated males (experimental embryos) were paired with FITC-labeled embryos from untreated males (control embryos) to form aggregation chimeras. The chimeras were cultured for 30-40 h and examined under phase-contrast and UV illumination for the number of unlabeled cells (from the experimental embryo) and total chimera cell number, which were then expressed as "proliferation ratios" (No. unlabeled cells/total chimera cell No.). Significant decreases in proliferation ratios were observed at postirradiation weeks 4, 6, and 7 for the 0.01-Gy dose group and at weeks 5-6 for the 0.05-Gy dose group. In addition, significantly lower ratios were observed with early and mid four-cell embryos, but not with late four-cell embryos. These results suggest that mouse male germ cells express a radiosensitive target(s) whose detection limit by the assay lies at an absorbed dose between 0.005 and 0.010 Gy for brief gamma irradiation and whose effect on embryonic cell proliferation might decay by the second cleavage. PMID- 1924729 TI - Distribution of 3H in rat conceptus cultured in vitro following brief administration of [3H]thymidine. AB - Rat embryos with intact visceral yolk sacs, explanted at 12 1/2 days of gestation, were cultured in vitro for up to 60 min in medium consisting of fetal calf serum, Eagle's MEM, and [3H]thymidine (1.2 kBq ml-1), using the roller bottle method. The total amount of 3H incorporated into the conceptus during the 60-min incubation was 79.2 Bq, and approximately 33, 23, and 44% of this activity was distributed to the embryo, the yolk sac, and the fluid in the exocoelom and amniotic cavity, respectively. The rate of 3H accumulation in conceptuses decreased with time in culture. It appeared that the decrease in the viability of the conceptus was not responsible for this phenomenon. The concentration of 3H in the yolk sac, i.e., 3H activity per gram wet weight, was 2.1 times that in the medium at the end of culture. In contrast, the 3H concentration in the embryo was significantly lower than that in the medium. These findings suggest that the visceral yolk sac of rat conceptuses may act as a barrier to the transport of tritiated thymidine between the medium and embryo. PMID- 1924730 TI - Irradiation in vitro discriminates between different O-2A progenitor cell subpopulations in the perinatal central nervous system of rats. AB - The effects of X irradiation on oligodendrocyte-type-2-astrocyte (O-2A) progenitor cells derived from different regions of the perinatal central nervous system (CNS) of rats were investigated in vitro. The O-2A progenitor cells can differentiate into either oligodendrocytes or type-2 astrocytes. The depletion of these cells could lead to demyelination, seen as a delayed reaction after irradiation of the CNS in vivo. To quantify cell survival, O-2A progenitor cells were grown on monolayers of type-1 astrocytes. Monolayers of type-1 astrocytes stimulate O-2A progenitor cells to divide. O-2A progenitor cells were irradiated in vitro and clonogenic cell survival was measured. The O-2A progenitor cells derived from perinatal optic nerve were quite radiosensitive in contrast to O-2A progenitor cells derived from perinatal spinal cord and perinatal corpus callosum. Furthermore, O-2A progenitor cells derived from the optic nerve formed smaller colonies, with most colonies showing early differentiation into oligodendrocytes. In contrast, more than half of the colonies derived from corpus callosum did not show any differentiation after 2 weeks in vitro and kept growing. These differences support the view that perinatal O-2A progenitor cells derived from the optic nerve are committed progenitor cells while the O-2A progenitor cells derived from the perinatal corpus callosum and the perinatal spinal cord have more stem cell properties. PMID- 1924731 TI - Accelerated heavy particles and the lens. VI. RBE studies at low doses. AB - We report on the prevalence, hazard, and relative biological effectiveness (RBE) for various stages of lens opacification in rats induced by very low doses of fast argon ions of LET 88 keV/microns, compared to those for X rays. Doses of argon ions from 0.01 to 0.25 Gy were used and RBEs of these ions relative to X rays estimated using a nonparametric technique. At the end of the follow-up period, which encompasses a significant fraction of the animals' lifetime, 90% confidence intervals for the RBE of the argon ions relative to X rays were 4-8 at 0.25 Gy, 10-40 at 0.05 Gy, and 50-100 at 0.01 Gy. Our results are consistent with the point-estimate neutron RBEs in Japanese A-bomb survivors, though broad confidence bounds are present in the Japanese results. If a reasonable extrapolation to higher doses is used, our results are also consistent with data reported earlier at higher doses for argon-ion cataractogenesis in rats, mice, and rabbits. We conclude from these results that at very low doses the RBE for cataractogenesis from HZE particles in space is considerably more than 20, and use of a quality factor of at least 50 would be prudent. PMID- 1924732 TI - Assessment of chronic gamma radiosensitivity as an in vitro assay for heterozygote identification of ataxia-telangiectasia. AB - Ataxia-telangiectasia (A-T) is a rare human autosomal recessive disorder characterized by, among other symptoms, catastrophic reaction to conventional radiotherapy. A-T heterozygotes are clinically asymptomatic and their fibroblasts are intermediate in radiosensitivity between homozygotes and normals. We have attempted to identify heterozygotes by assaying for cellular hypersensitivity to chronic gamma irradiation. Cultured dermal fibroblast strains from 13 control subjects and 55 members from a large Amish pedigree segregating for A-T were assayed for loss of colony-forming ability (CFA) in response to 137Cs gamma radiation delivered at a dose rate of 0.8 cGy/min. For each strain, multiple dose response curves were summarized in a composite D10 value (dose, in cGy, reducing colony survival to 10%). The D10's of the clinically normal controls and of those pedigree members with known A-T genotype formed a trimodal distribution, with the seven obligate heterozygotes displaying an average value (516 cGy) intermediate between that of the 10 healthy controls (797 cGy) and that of the two affected patients (154 cGy). The D10's were modeled statistically using Gaussian penetrance functions. The most parsimonious model yielded a significant difference in D10 means for heterozygotes and normal homozygotes, a significant donor age effect, but no sex effect. We compared probabilistic identification of heterozygotes based on D10 values with identification based on linkage data for two markers, THY1 and D11S144, closely linked to the A-T gene. This comparison revealed that the D10 data were appreciably less informative than the linked markers. Indeed, the extensive overlap between D10 values for heterozygotes and normal homozygotes precludes the use of postirradiation CFA for either accurate identification of heterozygotes or chromosomal mapping of the A-T gene. PMID- 1924733 TI - Neutrons revisited. Introduction. PMID- 1924734 TI - Neutron effects on the lens. AB - Few in vivo systems have received the investigative attention or have provided the grist for our understanding of basic radiobiological principles as have the lens and the cataract. From Roentgen's time the lens has been recognized as a "biological dosimeter" for gauging radiation response. Its advantages range from its in vivo status to its qualification as an integrated tissue. From the time of the Hiroshima/Nagasaki experience, there has been some urgency in attempting to understand the breadth of neutron-radiation effects on humans. The major obstacle has been our understanding of the doses which were received by the individuals who express the damage. The majority of the work has been derived from experimental animals and findings related to photons: X and gamma rays. Cataractogenesis provides insights in terms of not only ocular radiopathy but also the basic mechanisms of the action of radiation. Often referred to as the "classic" nonstochastic radiation effect, it is becoming increasingly clear that the suggestion of a threshold reflects the limitations imposed on expression by the life span. Thus the primary damage which appears to be a somatic mutation is fully stochastic. This being the case, it is not surprising that, as is the case for simpler systems, the RBEs for cataracts following neutron exposure are significantly higher than for X rays, and that there is evidence for an inverse dose-rate effect in their production. This presentation focuses on these data and on the merits of the lens for the assessment of neutron effects on humans, the existing data for known dose levels in the human population, and the confounding issues associated with extrapolation from experimental work. Data from Western sources as well as those from the USSR are presented. PMID- 1924735 TI - The slower cellular recovery after higher-LET irradiations, including neutrons, focuses on the quality of DNA breaks. AB - Data for many biological end points reviewed here indicate that the responsible lesions are not only more severe but also are often more slowly repaired as the LET of the ionizing radiation is increased. This is reflected in high RBE values for end points assayed at long (in contrast to short) times after irradiation, for example, residual injury in normal tissues and carcinogenesis. PMID- 1924736 TI - Neutron carcinogenesis in mice: a study of the dose-response curves. AB - Several experimental studies have been conducted with the objective to improve our knowledge of the types of dose-response relationships for radiation carcinogenesis in mice exposed to single acute doses. The experimental results on tumor induction have already been published and are here summarized with emphasis on the dependence on radiation quality, age at irradiation, and sex. These data indicate that the bone marrow, liver, and ovaries of the mice tested have an appreciable susceptibility to radiation carcinogenesis. However, the shape of the dose-response relationship depends on the tissue exposed. The data also confirm that a linear relationship is adequate for a conservative description of the dose effect curves after exposure to low dose of neutrons, while a purely quadratic dependence is not inconsistent with the experimental data obtained using low-LET radiation. Other information which stems from the present analysis is that the susceptibility to radiation induction of liver tumor by fission neutrons decreases in old age. Finally, the experimental data on induction of ovarian tumors suggest a threshold-like dose response. PMID- 1924737 TI - Life-shortening and disease incidence in mice after exposure to gamma rays or high-energy neutrons. AB - Male C57Bl/Cnb and BALB/c mice were exposed to single and fractionated d(50) + Be neutrons or 137Cs gamma rays at 12 weeks of age and were followed for life shortening and disease incidence as ascertained by autopsy and histological examinations at the time of spontaneous death. Fractionation schedules used were 10 exposures at 24-h intervals and 8 exposures at 3-h intervals for gamma rays, and 8 exposures at 3-h intervals for neutrons. The data were analyzed by the Kaplan-Meier procedure using as criteria causes of death and possible causes of death. Individual groups were compared by a modified Wilcoxon test according to Hoel and Walburg (J. Natl. Cancer Inst. 49, 361-372 (1972)). No significant difference was found in C57Bl/Cnb and BALB/c male mice between a single gamma-ray exposure and a single neutron exposure. Gamma-ray fractionation was clearly less effective in reducing survival time than a single exposure. In contrast, fractionation of neutrons was slightly, although not significantly, more effective in reducing survival time than a single exposure. The relative biological effectiveness (RBE) for life-shortening for d(50)-Be neutrons compared to gamma rays is of the order of 1 to 2 for a single exposure to neutrons and between 2 and 3 for fractionated neutrons compared to a single exposure to gamma rays. Neutron irradiation caused somewhat more cancer than gamma irradiation, and the RBE for cancer induction may be higher, probably between 2 and 3 in the range of 1 to 3 Gy, although the present data do not allow a more precise assessment. PMID- 1924739 TI - Relative biological effectiveness for neutron carcinogenesis in monkeys and rats. AB - The risks of total-body irradiation with large doses of X rays (average dose 6.7 Gy) and fission neutrons (average dose 3.4 Gy) were investigated by keeping a group of long-term surviving monkeys from an experiment on acute effects under continuous observation. On the basis of the number of animals developing tumors in each group as a function of the total observation period and the average absorbed dose, relative biological effectiveness (RBE) values between 4 and 5 have been derived at these high dose levels. In experiments on mammary carcinogenesis in rats the highest RBE values are observed for neutrons with energies of 0.43 to 1 MeV as produced by the p + T reaction or by the fission process. Based upon linear dose-response curves for neutrons and X rays, a maximum RBE value of 15 was observed for induction of adenocarcinomas in WAG/Rij rats. Appreciably higher RBE values would be obtained if the results of the gamma ray exposure, indicating a nearly quadratic dose-response relationship, were used as a baseline. For radiation protection applications it should be realized, however, that such an increase will be caused by the lower efficiency of low linear-energy-transfer radiation rather than by an increase in efficiency of the neutron irradiation at low doses. PMID- 1924738 TI - Protection by WR-151327 against late-effect damage from fission-spectrum neutrons. AB - The mutagenic and carcinogenic properties of fission-spectrum neutrons (KERMA weighted mean energy of 0.85 MeV) from Argonne National Laboratory's JANUS reactor are substantially greater than those of low-LET radiation sources such as X-ray and 60Co photons. However, in contrast to the vast amount of work focused on chemical protection against damage induced by low-LET radiation, studies on the prevention of carcinogenic damage induced by fission neutrons have been limited. We have investigated the protective properties of the thiophosphorate compound S-3-(3-methylaminopropylamino)propylphosphorothioic acid (WR-151327) against carcinogenesis and life shortening in the B6CF1 hybrid mouse strain. Male and female mice, 200 of each sex per experimental group, were irradiated individually at 110 days of age. WR-151327 was administered intraperitoneally at a dose of 580 mg/kg 30 min prior to irradiation with a dose of 10 cGy. Animals were housed five to a cage; cage locations in holding rooms were controlled by computer and randomized. Mice were checked daily and all deceased animals were necropsied. A neutron dose of 10 cGy significantly altered the patterns of death of male and female animals compared to corresponding unirradiated control groups (logrank P values of 0.01 and 0.07, respectively). This was evidenced by a shortening of the life span due to tumor induction in the irradiated groups. WR 151327, when administered 30 min prior to irradiation, effectively protected both male and female animals from these effects. The life curves of irradiated male and female animals and those of corresponding unirradiated control groups were not significantly different (logrank P values of 0.63 and 0.25, respectively). PMID- 1924740 TI - Cellular and molecular changes in mammary epithelial cells following irradiation. AB - The present paper describes experiments conducted over the last several years which have focused primarily on the development of mammary tumors in BALB/c mice after neutron and gamma irradiation. Time-dose relationships for induction of mammary and lung tumors following irradiation with fission-spectrum neutrons and 137Cs gamma rays are described. Subsequent studies have used in vivo/in vitro approaches to characterize cellular and molecular changes. These studies suggest quantitative and qualitative differences in the effects of neutrons and gamma rays. PMID- 1924741 TI - Issues about neutron effects: the JANUS program. AB - The impact of the biological end point selected as a synoptic measurement of mortality for the detection of protraction effects and the estimation of RBE values was investigated. Life shortening was chosen as an end point because it summarizes, in a single index, the cumulative effect of all injuries experienced by an organism. Cumulative mortality at a single time point and the hazard function (age-specific failure rate) were chosen to incorporate progressively more information, respectively, about the distribution of mortality through time. Data for both sexes of the B6CF1 mouse exposed to fission neutrons from the JANUS biomedical research reactor and 60Co gamma rays were analyzed. Three basic patterns of exposure were compared: single exposures, 24 equal once-weekly exposures, and 60 equal once-weekly exposures. The interpretation of results was influenced by the biological end point used as the synoptic measurement. An augmented response with protraction of the neutron exposure depended on the accumulated dose using the life-shortening response while this effect was nonexistent when cumulative mortality or the hazard function was used. A reduced effectiveness of protracted gamma-ray exposures was apparent for all end points. The hazard function analyses suggest that the time domain must be considered in the detection of protraction effects for either radiation quality and the subsequent estimation of RBE values. PMID- 1924742 TI - Neutrons at Hiroshima: how their disappearance affected risk estimates. AB - Since the 1960s, follow-up studies of the atomic bomb survivors have been the major source of quantitative information on the late effects of radiation on human health. Prior to 1986 these observations were misinterpreted in that the dose equivalent for survivors within 1600 m at Hiroshima (the proximal Hiroshima survivors) was thought to be due mainly to neutrons rather than to gamma radiation. The 1986 binational reassessment of atomic bomb dosimetry in Hiroshima and Nagasaki showed that neutrons made a minor contribution to the dose equivalent in both cities. The virtual elimination of neutrons as a causative factor for observed excess cancers among A-bomb survivors has had a profound effect on radiation risk estimates. Neither the high risks nor the linear dose response observed among proximal survivors at Hiroshima could be attributed to neutrons. Consequently, a linear-quadratic response pattern for the induction of solid cancers by gamma radiation is no longer supported by the Japanese experience. In this paper we explore why the neutron flux at Hiroshima was overestimated in the past, what was learned in the binational dose reassessment for Hiroshima and Nagasaki, and how this affected the recent risk assessment by the BEIR V committee. PMID- 1924743 TI - Therapy of infections in mice irradiated in mixed neutron/photon fields and inflicted with wound trauma: a review of current work. AB - When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, we developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60[Co sources. Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections. Combined therapy with S TDCM and ceftriaxone for K. pneumoniae infections in mice exposed to a mixed radiation field or to gamma rays was more effective than single-agent therapy. In all irradiated-wounded mice, single therapy of acquired infections with an antibiotic or S-TDCM did not increase survival. Survival of irradiated-wounded mice after topical application of gentamicin sulfate cream suggested that bacteria colonizing the wound disseminated systemically in untreated irradiated mice, resulting in death from sepsis. In lethal models of acquired infections in irradiated-wounded mice, significant increases in survival were achieved when systemic treatments with S-TDCM or gentamicin were combined with topical treatments of gentamicin cream. Therapies for sepsis in all mice exposed to a mixed field were less effective than in mice exposed to gamma rays. Nonetheless, the data show a principle by which successful therapy may be provided to individuals receiving tissue trauma in conjunction with radiation injury. PMID- 1924744 TI - The relative biological effectiveness of mixed fission-neutron-gamma radiation on the hematopoietic syndrome in the canine: effect of therapy on survival. AB - Acute lethality syndromes produced by the accidental exposure of humans to mixed neutron and gamma radiation from external sources can be related to acute lethality from photon irradiation using the relative biological effectiveness (RBE) for common end points. We used the canine as a model to study injury following exposure to mixed neutron and gamma radiation from the AFRRI TRIGA reactor. Exposures from the reactor were steady-state mode (40 cGy/min, bilateral) with an average neutron energy of 0.85 MeV; tissue-air ratio = 0.59 at midline abdominal. Healthy male and female canines were irradiated free-in-air behind a 6-in. lead wall; the neutron-gamma ratio was 5.4:1 at the entrance skin surface; exposures are reported as midline tissue doses. Bilateral exposure resulted in an LD50/30 of 153 cGy without therapeutic clinical support. Addition of clinical support consisting of fluids, antibiotics, and fresh irradiated platelets/whole blood increased the bilateral LD50/30 to 185 cGy, a dose modifying factor (DMF) of 1.21. This corresponds to respective LD50/30 values for bilateral 60Co gamma exposures of 260 and 338 cGy for nonsupported and clinically supported animals, and a DMF of 1.30. The RBE based on the values determined at midline tissue is approximately 1.69. Clinical support after bilateral irradiation produced a similar DMF to those of mixed fission neutrons and gamma rays and 60Co gamma rays alone. The RBE of 1.69 for midline tissue bilateral exposures is higher than 1, an RBE often cited for large animals. Therapeutic support administered to lethally irradiated canines significantly improved survival and increased the LD50/30 independent of radiation quality. PMID- 1924745 TI - The historical background for large-animal studies with neutrons of various energies. AB - Studies of the biological effects of fast neutrons were started as soon as adequate sources became available, and the first of these was the cyclotron at Berkeley. Limitations on methods for physical dosimetry render most of the earliest studies nearly useless, and the first landmark studies with modern methodology were done at Berkeley in the 1950s. This report is an attempt to review and summarize all the work that took place from 1950 to 1965. The RBE for fast neutrons in the dog is generally in the range of 1.0 or less, depending upon reference radiation, the biological end point chosen, and the exposure geometry. Also the RBE seems to be relatively independent of the fast-neutron spectrum, at least for the range of values that has been studied. Mean after-survival times in irradiated dogs and goats indicate that the bone marrow syndrome usually predominates in large animals irradiated with fast neutrons. The gastrointestinal threshold for the dog is around 1200 cGy, and for neutrons the biological effectiveness for the GI syndrome still does not bring the GI threshold down to the point where it predominates over the bone marrow syndrome. As expected from biological first principles, for dose rates in excess of a few tens of centigrays per minute, dose rate seems to have no effect on the outcome with either neutron, gamma or X irradiations when the end point is lethality. PMID- 1924746 TI - Radiation sensitivity of the hemopoietic stem cell. AB - The LD50/30 after total-body irradiation (TBI) indicates the radiosensitivity of any animal species and is determined by the number and radiosensitivity of the hemopoietic stem cells, in particular those that are pluripotent. The most extensive information exists for the mouse because in the species the pluripotential stem cells can be enumerated by the spleen colony assay. Stem cells of various species can also be quantified in vitro by the CFU-S and CFU-C assays. With the latter assay, the reported values for D0 and N vary by factors of 2-3 and up to 5, respectively. In both assays the upper level of the range of doses is about 5 Gy. A theoretical approach for the calculation of the D0 of hemopoietic stem cells was previously developed by comparing the number of autologous or syngeneic bone marrow cells required to protect 50% of supralethally irradiated animals with the known LD50/30 of the species and the estimates of total number of bone marrow cells present before irradiation. Using the rate of repopulation of peripheral blood cells in monkeys following high-dose TBI and the repopulation of the spleen and the bone marrow in mice, we have derived estimates of the surviving fractions of hemopoietic stem cells at radiation doses between 5 and 10 Gy. The resulting data suggest, among other possibilities, the presence of a small subpopulation of hemopoietic stem cells with higher radioresistance than the majority of the stem cells. It was postulated that this small subpopulation may exist under hypoxic conditions. To test this hypothesis, RBEs for fission neutrons have been determined for CFU-S survival and for LD50/30 in BCBA mice. Both RBEs were very similar, which proves that the radioresistance of the subpopulation responsible for survival at high doses is not due to hypoxic conditions. PMID- 1924747 TI - The response of dogs to mixed neutron-gamma radiation with different n/gamma ratios. PMID- 1924748 TI - Physical, biophysical, and cell-biological factors that can contribute to enhanced neoplastic transformation by fission-spectrum neutrons. AB - In radiobiology, fission-spectrum neutrons frequently have been used as a surrogate for other high-LET radiations, particularly when thick absorbers were involved as in animal studies. However, the spectrum of proton secondaries, plus the gamma rays generated in the absorption processes, suggests that a characterization of such a beam, based upon an average LET alone, may not adequately account for the spectrum of biological properties that it may have. Conflicting results have been reported on the relative effectiveness of reduced dose rates of fission-spectrum neutrons, and other high-LET radiations, for the induction of noeplastic transformation of cells in culture. Enhanced rates of neoplastic transformation were reported for C3H 10T1/2 mouse cells, Syrian hamster embryo cells, and human hybrid cells-all with the same beam of fission spectrum neutrons generated by the JANUS reactor at the Argonne National Laboratory. No enhancement was observed with C3H 10T1/2 cells exposed to the beam from the TRIGA reactor at the Armed Forces Radiobiological Research Institute, or to maximally effective alpha particles. The recent report that an enhancement was also observed when human hybrid cells were exposed at a low dose rate to the TRIGA beam indicated that physical factors alone were not responsible for the differences observed with C3H 10T1/2 cells exposed to these various beams. To resolve the lack of consistency in the results that had been reported, a biophysical model was developed based, in part, on the existence of a narrow age interval in the growth cycle of a cell during which it is particularly sensitive to radiation neoplastic transformation. Because of the special physical and biological properties of cells in M phase, and/or in late G2 phase or early G1 phase, these cohorts of cells were proposed as those that are hypersensitive to neoplastic transformation by radiation. PMID- 1924749 TI - Energy and dose-rate dependence of neoplastic transformation and mutations induced in mammalian cells by fast neutrons. AB - Since our original observation that low-dose, low-dose-rate JANUS neutrons produced more transformation in C3H 10T1/2 cells than equivalent doses at high dose rate (Hill, Buonaguro, Myers, Han, and Elkind, Nature 298, 67-69, 1982), there have been many reports on the dose-rate dependence of a variety of high-LET radiations. Some of these have qualitatively supported our original and subsequent observations, and some have found no evidence for a dose-rate effect. Thus there remain questions about the generality, size, tissue specificity, and reproducibility of these observations. Furthermore, there are no well-established mechanistic descriptions or observations to account for such effects. In this report studies are presented using a range of neutron energies produced by the UCLA cyclotron from 12- to 46-MeV protons on beryllium. In particular, emphasis is placed on comparing results between energies for neoplastic transformation and mutation end points, and preliminary data are presented on the molecular and mechanistic aspects of neutron-induced damage. PMID- 1924750 TI - Oncogenic transformation of C3H 10T1/2 cells by acute and protracted exposures to monoenergetic neutrons. AB - An in vitro assay was used to assess cell killing and induction of neoplastic transformation in C3H 10T1/2 cells exposed to X rays and a range of monoenergetic neutrons administered at various dose rates. Curves for cell survival and induction of neoplastic transformation showed nonlinearity for cells exposed to acute graded doses of X rays, while irradiation of cells with 0.05 to 1.5 Gy of 0.23-, 0.35-, 0.45-, 0.70-, 0.96-, 5.90-, and 13.7-MeV neutrons resulted in a linear response as a function of dose for both neoplastic transformation and killing. When compared to results obtained with 250-kVp X rays, all neutron energies were more effective at both cell killing and induction of neoplastic transformation. When expressed as maximum biological effectiveness (RBEM), both cell survival and induction of neoplastic transformation showed an initial increase with neutron energy (maximal at 0.35 MeV), followed by a decrease in effectiveness with further increases in energy. These responses are consistent with microdosimetric predictions in that recoil protons from neutron interaction are shifted to lower lineal energies as neutron energies increase. To examine the effects of temporal distribution of dose on neutron-induced neoplastic transformation, cells were exposed to either a single dose or five equal dose fractions spread over 8 h. As a function of dose for single or fractionated exposures to 0.5 Gy or 0.23-, 0.35-, 0.45-, 5.9-, or 13.7-MeV neutrons, neither a sparing nor an enhancing effect was seen with survival. Similarly, the frequency of induction of neoplastic transformation was independent of dose fractionation for all but 5.9-MeV neutrons. The enhancing effects of exposure to fractionated doses of 5.9-MeV neutrons were further studied by comparing exposures for a range of doses given singly, in five fractions over 8 h, or continuously for 8 h. Results reaffirm the enhancing effects of dose fractionation on the induction of oncogenic transformation for 5.9-MeV neutrons. Within the limits of the data, there is modest enhancement of neutron-induced neoplastic transformation when the exposure dose is extended from a few minutes to several hours, with the enhancement being dependent on neutron energy. PMID- 1924751 TI - Neutron dose-rate experiments at the AFRRI nuclear reactor. Armed Forces Radiobiology Research Institute. AB - Some in vitro and in vivo studies with neutrons have shown increased carcinogenic effectiveness following low-dose-rate or fractionated irradiation compared to acute exposure in the low-dose range. This would imply that the risk of cancer for persons exposed occupationally to low doses of neutrons is underestimated at present. The C3H 10T1/2 assay has played a major role in investigating neutron dose-rate effects. We describe three independent series of experiments addressing the question of the influence of dose rate using the AFRRI fission-neutron source with the C3H 10T1/2 cell transformation assay as well as with two mutation assays utilizing human-hamster hybrid AL cells. In the first two series, we focused on performing experiments with fission-neutron doses and dose rates similar to those for which enhancement of neoplastic transformation of C3H 10T1/2 cells was originally reported, and observed no discernible dose-rate effect. In the third series concurrent with the induction of neoplastic transformation in C3H 10T1/2 cells, we also measured mutagenesis at two loci in AL cells. Data for survival, neoplastic transformation, and mutation were obtained at two dose rates in the range of neutron doses 0.005 to 0.9 Gy. Dose-rate effectiveness factors expressed as ratios of the effect for low compared to high dose rate did not differ from one, indicating no influence of dose rate on these end points. PMID- 1924752 TI - Effect of fission-neutron dose rate on the induction of a tumor-associated antigen in human cell hybrids (HeLa X skin fibroblasts). AB - The HeLa X skin fibroblast human cell hybrid system has been used to study the effect of fission-neutron dose rate on the induction of neoplastic transformation. Previously published data using neutrons from the JANUS reactor at Argonne National Laboratory are compared with some preliminary data obtained on the TRIGA reactor at the Armed Forces Radiobiology Research Institute. Comparable results were obtained on both reactors, both in terms of absolute values of transformation frequency and in terms of magnitude of the inverse dose rate effect (a factor of 2.5 to 3). PMID- 1924753 TI - Neoplastic transformation and the inverse dose-rate effect for neutrons. AB - Considerable evidence has recently accumulated, both in vivo and in vitro, to suggest that neutrons at low dose rates, or in multiple fractions, have an enhanced effectiveness for inducing neoplastic transformation. A consistent pattern has emerged as to the dependence of the effect on dose, dose rate, and radiation type. A consistent model of the phenomenon as a function of dose, dose rate, and radiation type is presented. The approach, first suggested by Rossi, is that cells are extra sensitive in part of their cycle. Then an acute exposure of cycling cells to high-LET radiation results in some fraction of the sensitive cells receiving large depositions of energy--greater than required for the effect. If the exposure is protracted, a larger proportion of sensitive cells will be exposed, but to smaller numbers of energy depositions--still enough, however, to produce the effect. The model produces results consistent with all available data on enhancement of neoplastic transformation in the C3H 10T1/2 system by protraction or fractionation at medium or high LET. Implications for radiation protection and the radon problem are discussed. PMID- 1924754 TI - Probing altered hematopoietic progenitor cells of preleukemic dogs with JANUS fission neutrons. AB - Protracted courses of low-daily-dose gamma irradiation elicit high incidences of myeloproliferative disease, principally myeloid leukemia (ML), in beagle dogs. A four-phase preclinical sequence in the induction of ML has been described: (1) suppression, (2) recovery, (3) accommodation, and (4) preleukemic transition. Within this sequence, a critical "early"-occurring hematopoietic target cell event that promotes progression of preclinical phases I and II has been identified and characterized by an acquisition of increased radioresistance to low-LET gamma rays by granulocyte/monocyte lineage-committed progenitor cells (CFU-GM). To gain further insight into the basis of this critical event, the acquired survival response of preleukemic progenitor cells has been probed in vitro with high-LET fission neutrons. For these studies, marrow CFU-GM were isolated from chronically irradiated preleukemic dogs, as well as from nonirradiated controls, subjected to graded doses (0-300 cGy) of either JANUS fission neutrons or 60Co gamma rays, and assayed for survival by a standard cloning assay. Major observations resulting from these assays include the following. First, the acquired radioresistance of preleukemic CFU-GM to low-LET gamma rays noted previously extends to high-LET fission neutrons as well. Relative to control CFU-GM exhibited small but significant increases in radioresistance of about 10 cGy with an average D0 value of 38 (+/- 2.3) cGy for preleukemic CFU-GM, and 28 (+/- 1.3) cGy for the control levels, the CFU-GM irradiated within a marrow dose range of 10-75 cGy. Second, at higher neutron doses (150-600 cGy), fractional survival of both control and preleukemic CFU-GM declined nonexponentially, suggesting the existence of a small, radioresistant subpopulation constituting about 2% of the total marrow CFU-GM within normal nonirradiated dogs, and a 15% fraction of the progenitor cell population in preleukemic marrow (preclinical phases II-IV). The latter is most likely the result of a normally minor subpopulation gaining a growth advantage due to its inherent radioresistance and clonally expanding in the strong selective pressure of chronic marrow irradiation in vivo. We speculate that these qualitative/quantitative changes in the function of progenitor cells foster the initiation of aberrant regenerative hematopoiesis characteristic of early evolving radiation leukemogenesis. PMID- 1924755 TI - Perspectives on fast-neutron mutagenesis of human lymphoblastoid cells. AB - The effects of low-fluence exposures to (Pu, Be) neutrons (En = 4.2 MeV) have been studied in a sensitive human B-lymphoblastoid cell line, TK6. Mutations were scored for two genetic loci, hypoxanthine phosphoribosyltransferase (hgprt) and thymidine kinase (tk), as a function of dose and dose rate. For exposures limited to less than one cell cycle, the mutation frequency for the hgprt locus was 1.92 X 10(-7)/cGy. When exposures were protracted over multiple cell generations, mutation yields were increased to 6.07 X 10(-7)/cGy. Similar yields were obtained for the induction of tk-deficient mutants with a normal cell generation time (tk ng) when exposures were carried out at very low dose rates over multiple cell generations. In the series of data presented here, the results obtained for short duration neutron exposures are compared with data obtained for monoenergetic heavy charged particles of defined linear energy transfer (LET) produced at the BEVALAC accelerator at Lawrence Berkeley Laboratory. TK6 cells have been exposed to beams ranging in atomic number from 20Ne to 40Ar over an energy range from 330 to 670 MeV/amu. Mutation induction was evaluated for both loci for a subset of these beams. The results obtained with 20Ne ions of 425 MeV/amu (LET = 32 keV/microns) and 28Si ions of 670 MeV/amu (LET = 50 keV/microns) closely resemble the mutation yields obtained for brief exposures to (Pu, Be) neutrons. The nature of alterations in DNA structure induced within the tk locus of tk-ng mutants is reviewed for a series of neutron-induced mutants and a series of mutants induced by exposure to 40Ar ions (470 MeV/amu, LET = 95 keV/microns). The mutational spectra for these two types of mutants were similar and were dominated by allele loss mutations. Multilocus deletions inclusive of the c-erbA1 locus were common among tk-deficient mutants induced by these densely ionizing radiations. For the mutants induced by 40Ar ions, it is likely that the mutations were produced by the traversal of the chromosome by a single particle. PMID- 1924756 TI - Severity of organ injury as a predictor of acute mortality for disparate patterns of absorbed dose distribution. AB - Nonuniform distribution of absorbed dose is frequently encountered in the irradiated mammal; the degree of nonuniform distribution is generally more severe as the size of the animal increases and the energy or penetrating power of the radiation decreases. However, acute mortality under these conditions, e.g., from the hematopoietic syndrome, appears not to be consistently predictable from the dose at any given location or locations within the animal. It is thus reasonable to seek a biological quantity that may be adequate for this purpose. Accordingly, it was postulated that, in animals dying from the bone marrow syndrome, survival is determined by the total number of viable stem cells remaining in the entire body, independent of their distribution. To test this hypothesis, the LD50/30 value for mice exposed to nonuniform irradiation of varying degrees of severity was obtained, as was that for mice receiving uniform total-body irradiation. The distribution of bone marrow in transverse segments of tissue along the spinal axis was determined, as was the dose to each of the segments. The data were analyzed by multiplying, for each segment, the fraction of stem cells in the fraction of cells surviving, as determined from the dose and a survival curve for stem cells determined separately. The sum of these products yielded the surviving number of stem cells in the total mouse, for both the uniformly and nonuniformly exposed animals. The surviving fraction was found to differ by no more than 20%; this was taken to be reasonable evidence that, based on the number of surviving stem cells, it is possible to predict the mortality rate for both uniform and markedly nonuniform irradiation. PMID- 1924758 TI - [Clinical aspects of laryngeal imaging techniques]. AB - The surgical anatomy and physiology of the larynx, some typical diseases that affect it, and the clinical diagnostic procedures are reviewed. The emphasis is on the aspects useful in deciding whether diagnostic imaging is indicated and interpreting the images. The diagnostic tools of the ENT clinician are therefore described, with reference to what can be diagnosed easily and what questions may remain open and can better be solved by imaging procedures. PMID- 1924759 TI - [The poor man's laryngogram]. AB - This paper is a reassessment of an old method improved by well-directed application of well-known maneuvers of laryngo-pharyngeal function. Although not as visually attractive as a dedicated laryngogram (now hardly ever requested), it does render similarly reliable diagnostic information, which, supported, as occasionally necessary, by conventional tomography, can even surpass that given by the older technique. Its main advantage lies in providing cheap, quick, noninvasive studies with minimal discomfort for the patient. Should further investigation be necessary, for analysis of deep extension, modern cross sectional imaging methods (especially MR) far surpass even dedicated laryngography in diagnostic value and can be based adequately on "poor man's laryngography". Ways in which this method may be optimized, especially those involving laryngo-pharyngeal function, are briefly presented--with emphasis on relevant practical aspects--as are normal and abnormal findings. PMID- 1924757 TI - Basic radiobiological investigations of fast neutrons. AB - The radiobiological properties of a cyclotron-produced 43-MeV (p----Be) fast neutron beam relative to gamma rays have been investigated using Chinese hamster V79 cells in culture. As expected, the relative biological effectiveness (RBE) of this neutron beam for cell killing was shown to increase as dose decreased, and the effectiveness per unit dose was slightly less compared to a 25-MeV (d----Be) neutron beam. By tracing single cells that formed microcolonies after irradiation, we found cell proliferation kinetics to be retarded to a greater extent by fast neutrons than by gamma irradiation. Following either neutron or gamma irradiation, a fraction of the irradiated cells failed to divide in the first postirradiation division and another fraction could produce as many as four generations of progeny before proliferation stopped. The properties of these cells presumed to be destined for death suggest that more than one mechanism and/or multistep process underlies the radiation-induced proliferative death. The fast-neutron beam was also found to be more effective quantitatively than gamma rays in producing DNA double-strand breaks (DSBs, measured by nondenaturing filter elution), and G1-phase chromosome fragments (measured by the premature chromosome condensation technique). However, the reverse was observed for DNA single-strand breaks (SSBs, measured by alkaline filter elution or hydroxylapatite uncoiling). Interestingly, both fast neutrons and gamma rays produced a large component of SSBs and DSBs with a fast-rejoining time constant of about 2-5 min, which appears to be independent of dose. The latter results could not resolve the possibility of lengthening the repair-time constant by increasing radiation dose within the range that is reflected by the shoulder of the survival curve, and consequently did not support the idea of repair saturation as a mechanism for the presence of the shoulder. The RBE for the hypoxanthine phosphoribosyl transferase mutation frequency per survivor at the 10% survival level was estimated to be 2.5, a value that is comparable to the RBE (2.1) for cell killing at the same survival level. Although most of the above mentioned findings are compatible qualitatively with the relatively high-LET (linear energy transfer) nature associated with the fast-neutron beam, the significance of the action attributable to the mixture of LET could not be delineated in these experiments. Further, the biological significance of DSBs and chromosome aberration and the molecular mechanisms responsible for the repair and expression of these damaging processes remain to be elucidated. PMID- 1924760 TI - [Radiologic findings following supraglottic and total laryngectomy]. AB - The treatment of carcinoma of the larynx has recently been greatly improved with the development of supraglottic and total laryngectomy. This has also led to a high five year survival rate. The normal postoperative radiological appearances are presented together with the spectrum of relevant radiological investigations and their indications. The most frequently seen postoperative complications and findings in patients with dysphagia are described with special reference to pharyngograms and cineradiography. The morphology of the vibrating segment after laryngectomy in patients who do not develop effective alaryngeal speech is demonstrated. PMID- 1924761 TI - [Radiotherapy of laryngeal cancer]. AB - The specific anatomical and biological situation of larynx cancer gives radiotherapy an important part in primary management of this tumour. In early stages (T1, T2) surgery and radiotherapy achieve equivalent survival, but with the latter, normal speech can be maintained in most cases. Treatment techniques for supraglottic and glottic cancers differ due to their different risk of lymphatic spread. Local relapse is between 10 and 30% depending on extent and localisation of the tumour, but 3/4 of these patients can be salvaged by surgery. In advanced laryngeal cancer a combination of surgery and irradiation is the mainstay of treatment. New radiation options, especially hyperfractionated irradiation, seem to achieve local control even in advanced disease. The good results of local treatment expose the considerable risk of second malignancies (particularly all lung cancer) in this group of patients. PMID- 1924762 TI - [Parathyroid sonography in long-term dialysis]. AB - In a prospective study the prevalence of sonographically enlarged parathyroid glands in patients on maintenance hemodialysis was investigated and correlated with clinical and laboratory findings of secondary hyperparathyroidism. We examined 97 unselected patients with a 5 MHz probe. In 34% (33/97) a total of 69 parathyroid glands were detected with a statistically significant correlation between the period of dialysis and the incidence of parathyroid enlargement; 47.8% of the glands were hypoechoic, 34.8% moderately echogenic and 17.3% gave echoes similar to the normal thyroid parenchyma. A correlation was found between the finding of enlarged parathyroid glands and blood levels of calcium and alkaline phosphatase. Parathyroid enlargement was found sonographically before, or in the absence of clinical and laboratory findings of secondary hyperparathyroidism. Sonography is therefore a useful technique for early diagnosis of hyperparathyroidism in patients on maintenance dialysis. PMID- 1924763 TI - [Arterial collateral pathways in liver cirrhosis and celiac axis occlusion]. AB - We describe the arterial supply in a patient with cirrhosis of the liver, occlusion of the coeliac axis and with a replaced right hepatic artery from the superior mesenteric artery. Six arterial pathways between the mesenteric and hepatosplenic axis were demonstrated, and hepatofugal blood flow was shown in spite of coexistent portal hypertension. PMID- 1924765 TI - [CT diagnosis of inferior vena cava anomalies. The azygos continuation]. AB - The azygos continuation is a rare variation of the inferior vena cava (IVC), usually associated with cardiac anomalies. We report CT in two female patients with no cardiac disease. One had no further visceral abnormalities, while the other had polysplenia agenesis of the left lobe and a hypertrophic right lobe of the liver. This complex of anomalies has been demonstrated for the first time by imaging. Our cases show the variation of anomalies associated with azygos continuation. When planning therapeutic procedures (for example cava filtration) these anomalies are relevant. CT is sufficient for their demonstration and in most cases there is no need for confirmation by invasive methods. PMID- 1924764 TI - [Aortobronchopulmonary fistula following a pulmonary contained aortic rupture in patients with a thoracic aortic aneurysm and severe aortic sclerosis]. AB - Rupture of the thoracic aorta is usually widespread and fatal. Rupture limited by the lung and aorto-bronchopulmonary fistula are rare. We report two patients with a contained perforation of the thoracic aorta, who presented with haemoptysis. Chest radiographs demonstrated an aortic aneurysm and pulmonary haemorrhage in the first, while in the other perforation of an atherosclerotic aorta with a pulmonary haematoma was misinterpreted as bronchial carcinoma. In both cases contrast enhanced CT clearly demonstrated the abnormality in the aorta and the pulmonary haemorrhage. Since aortography often fails to demonstrate a perforation, CT or MRI should be performed early in patients with suspected rupture of the thoracic aorta. PMID- 1924766 TI - [Left parieto-occipital tumor of the skull]. PMID- 1924767 TI - Mammographic compression: science or art? PMID- 1924768 TI - Endoscopic US in the staging of esophageal and gastric cancer. PMID- 1924769 TI - The trouble with spectroscopy papers. AB - Writing a critique and guide for authors of clinical spectroscopy research papers is a likely way of ensuring that one never sees another of one's own papers published in this field. Nevertheless, it is disappointing, though perhaps predictable, that despite its historical foundations in quantitative spectroscopy, the field has its fair share of findings that are not so obviously reconciled. Here is the view of one author, one referee, and one spectroscopy protagonist about what might be expected of a clinical spectroscopy paper. In addition to novelty, the fundamental criteria for acceptance should be that the conclusions are supported by properly and objectively quantified results, and that sufficient experimental detail is provided so that one skilled in the art could reproduce the study and its findings. PMID- 1924770 TI - Compression US in isolated calf venous thrombosis. PMID- 1924771 TI - Measurement of force applied during mammography. AB - The discomfort that patients experience during mammography is probably related to a variety of factors, one of which might be the amount of compression used. The authors measured the amount of force applied to the breasts during mammography and the resulting breast thickness in 560 women and correlated these measurements with the patient's subjective impression of the examination. The amount of force applied ranged from 49 to 186.2 N (median, 122.5 N). Breast thickness ranged from 10 to 88 mm (median, 46.5 mm). Forty-seven women (8%) rated the examination as painful (ie, mammography was either "very uncomfortable" or "intolerable"). Logistic regression analysis revealed a highly significant relationship between probability of a painful response and ratio of force to thickness (P = .007). Current guidelines suggest that maximum available force be at least 160 N but not more than 200 N. However, because increasing force is associated with increasing likelihood of pain, technologists should be aware that these recommended maximum limits are not intended to be used routinely for all women. In this study, high quality mammograms were obtained in a majority of women with forces less than the maximum available level. PMID- 1924772 TI - Rate of compliance with recommendations for additional mammographic views and biopsies. AB - All recommendations for immediate additional studies and biopsies following routine mammography during a 6-month period were reviewed retrospectively to establish compliance rates and determine the time intervals for completion of the recommendations. During this period, 5,693 mammograms were obtained. Additional mammographic studies and biopsies were recommended for 364 (6.4%) and 180 (3.2%) of all patients, respectively. The compliance rates were 99.7% (n = 363) for additional studies and 98.9% (n = 178) for biopsies. Additional studies and biopsies were completed within 30 days of the recommendations in 98.4% (n = 358) and 91.7% (n = 165) of the patients, respectively. Compliance with recommendations for additional studies within relatively short periods can be maximized by having the mammographic facility schedule examinations directly with the patients. Compliance with biopsy recommendations can be optimized by directly contacting the referring physician. Follow-up written reports should specifically state that a biopsy is recommended and that this has been discussed directly with the referring physician. PMID- 1924773 TI - Lobular carcinoma in situ: mammographic-pathologic correlation of results of needle-directed biopsy. AB - The mammographic and histologic findings were reviewed in 41 consecutive cases of isolated lobular carcinoma in situ (LCIS) unassociated with any malignant diagnosis. Thirty-one needle-directed breast biopsies were performed to evaluate clustered microcalcifications. In 24 of the 31 cases, the calcifications were found in areas of benign breast disease, with LCIS representing a separate process. In the few cases in which microcalcifications were seen in association with LCIS, a greater number of similar calcifications were present in adjacent benign disease. Soft-tissue abnormalities necessitating the performance of a biopsy represented benign foci, except in one patient with LCIS in and adjacent to a fibroadenoma. The authors conclude that LCIS has no characteristic mammographic features. LCIS is detected as an incidental finding at breast biopsy, with the mammographic abnormality predominantly reflecting a benign process. PMID- 1924774 TI - Assessment of pulmonary airway reactivity with high-resolution CT. AB - The evaluation of airway reactivity plays a central role in the diagnosis of bronchial hyperreactivity and asthma. The authors used high-resolution computed tomography (HRCT) to assess airway reactivity and compared the results with simultaneously performed measurements of airway pressure (Paw). Ten anesthetized and ventilated dogs were studied in a control state, after saline aerosol application, and after histamine aerosol challenge. In each condition, Paw was determined and HRCT was performed at functional residual capacity. On the HRCT scans, the cross-sectional areas of airway lumina were measured by using a computer edging process. After histamine challenge, HRCT demonstrated a decrease in airway areas of 43% +/- 2% (mean +/- standard error) from baseline (control) and Paw increased 99% +/- 18%. Surprisingly, saline aerosol challenge also resulted in a significant decrease in airway areas (26% +/- 3%) from control, while Paw measurements did not change significantly. Airway reactivity varied between dogs and within dogs. The authors conclude that HRCT can depict the site and degree of airway reactions and thus represents a new tool to assess airway reactivity in vivo. PMID- 1924775 TI - Thymic involvement in Hodgkin disease: CT and sonographic findings. AB - To evaluate the morphologic characteristics and frequency of thymic enlargement in Hodgkin disease, the initial and follow-up computed tomographic (CT) scans of 43 patients with newly diagnosed Hodgkin lymphoma were retrospectively analyzed. Sonograms of the thymic region in 21 patients were also available and were compared with the CT scans. Initial CT scans showed thymic enlargement in 17 of the 43 patients, no evidence of thymic enlargement in 15 patients, and equivocal findings in 11 patients. Analysis of follow-up CT scans indicated that seven of the 11 patients with initially equivocal findings had had thymic enlargement. In all seven patients, the anterior mediastinal tumor shrank with therapy and adopted a typical tongue-shaped thymic configuration. In nine of the 24 patients with thymic enlargement, the thymus remained enlarged after therapy and full clinical remission. The comparison of sonograms and CT scans showed that sonography could not help differentiate the normal-size thymus from surrounding fatty tissue. All thymic glands that were considered diseased because of enlargement at CT were sonographically visible due to an abnormal, hypoechoic structure. The results of the study show that thymic enlargement presumed to be due to involvement by Hodgkin disease seems to occur more frequently than previously reported. PMID- 1924776 TI - Effect of patient positioning after needle aspiration lung biopsy. AB - Fifty-five patients who underwent fluoroscopically guided needle aspiration lung biopsy were randomly assigned to one of two postbiopsy treatment groups: Patients were placed recumbent with puncture site either down (n = 36) or up (n = 19) for at least 1 hour. No significant difference in pneumothorax rate was seen between the two groups. Chest tube placement, however, was required in 21% (four of 19) of the puncture-site-up group versus 3% (one of 36) of the puncture-site-down group, which was a significant difference (P = .04). Puncture-site-down postbiopsy positioning reduces the proportion of patients requiring chest tube placement after lung biopsy. PMID- 1924777 TI - Effect of tendon orientation on MR imaging signal intensity: a manifestation of the "magic angle" phenomenon. AB - To determine whether orientation in the static field may be responsible for the frequent occurrence of increased signal intensity within normal tendons at magnetic resonance (MR) imaging, seven healthy volunteers were imaged by means of a 1.5-T unit and standard clinical pulse sequences. The wrist, ankle, and shoulder regions were evaluated with local coils. Imaging was performed with tendon orientations ranging from 0 degree to 90 degrees in relation to the constant magnetic induction field (B0). Markedly increased intratendinous signal intensity was observed at the "magic angle" of 55 degrees, intermediate signal intensity was observed at 45 degrees and 65 degrees, and no signal intensity was observed at 0 degree and 90 degrees. Signal intensity was evident only when a short echo time was used. The authors believe that tendon orientation greatly affects tendon signal intensity in vivo. Increased signal intensity due to the magic angle effect may be misdiagnosed as tendinous degeneration, tendinitis, or frank tear. PMID- 1924779 TI - Triangular fibrocartilage and intercarpal ligaments of the wrist: MR imaging. Cadaveric study with gross pathologic and histologic correlation. AB - To provide further understanding of the magnetic resonance (MR) signal intensities in the triangular fibrocartilage (TFC) and interosseous ligaments of the wrist, the authors performed MR imaging with gross pathologic and histologic analysis in 10 cadaveric wrists. Spin-echo T1- and T2-weighted coronal images were obtained, and 3-mm coronal sections of the specimens were then made that correlated precisely with the MR images. Normal portions of the TFC showed asymmetrical bow tie-like low signal intensity, except near the radial and ulnar attachments. Degeneration of the TFC, present in all cases, was more severe on the proximal surface and was characterized by high signal intensity on T1 weighted images and less high signal intensity on T2-weighted images. These findings differed from those in TFC perforation, which showed high signal intensity on T2-weighted images. Similar signal intensity characteristics could allow differentiation of degeneration and perforation of the scapholunate and lunotriquetral ligaments. These findings suggest that in vivo MR imaging may accurately delineate degeneration and perforation of the TFC and intercarpal ligaments. PMID- 1924778 TI - High-resolution, short echo time MR imaging of the fingers and wrist with a local gradient coil. AB - The many fibrous tissues of the wrist and hand have short T2s, and, because of the small size of the tissues, their magnetic resonance (MR) imaging necessitates use of the high spatial resolution obtainable with fields of view as small as 2 cm x 2 cm x 1 mm. The authors demonstrate that the use of a local xyz gradient coil, positioned off-center in a clinical MR imager to facilitate patient positioning, permits acquisition of high-resolution images in spin-echo (SE) and gradient-recalled-echo (GRE) sequences with echo time (TE) as short as 6 msec (SE) or 3 msec (GRE). The authors compare this method for obtaining high resolution images with the alternative method of using normal gradient strengths and increased pulse duration. The effects on image quality of TE, bandwidth, gradient strength, and chemical shift artifacts are presented. Images obtained with the local gradient coil of the carpal tunnel, carpal bones, and proximal interphalangeal joint in healthy volunteers are shown. PMID- 1924780 TI - Sciatic nerve: sonographic evaluation and anatomic-pathologic considerations. AB - Sonographic analysis of the sciatic nerve was performed in vitro (anatomic specimen), in vivo (healthy volunteers), and in 16 patients with suspected peripheral sciatic nerve lesions. The ultrasound (US) examinations were performed with standard and high-resolution US equipment with linear-array configuration. The normal nerve displayed an echogenic fibrillar texture with round cross sectional structure on both in vitro and in vivo sonograms. Satisfactory delineation of the nerve was obtainable in all cases. Nerve displacement was the main sonographic finding in cases of extrinsic compression. The lesion displayed variable echotexture, ranging from hypoechogenicity or mixed echogenicity in hematomata to hyperechogenicity in cases of fibrosis. Primary nerve tumors (neurofibroma) or infiltrating tumors (desmoid) caused clear disruption of the nerve structure. Use of sonography enabled assessment of the continuity of the nerve margins with the interposed graft in a case of reconstructive surgery. The potential to image sciatic nerve lesions noninvasively may have an important impact on diagnosis, treatment, and prognosis in symptomatic patients. PMID- 1924781 TI - Cortical bone metastases. AB - The bone scans and radiographs of 27 patients with solitary or multiple cortical bone metastases were retrospectively studied. Thirty-six cortical metastases were identified in 32 appendicular long bones. Origin of the tumors included lung, breast, kidney, pancreas, larynx, uterus, and site unknown. Cortical metastases have hitherto been reported as individual cases or in small numbers. The large number reported herein suggests that the occurrence of these lesions may be more common than previously expected. A cortical metastasis was the only evidence of metastatic disease in eight of the 27 patients. PMID- 1924782 TI - Skeletal brucellosis: assessment with bone scintigraphy. AB - To assess the usefulness of bone scintigraphy in the detection of bone and joint abnormalities in brucellosis and show the pattern and frequency of such abnormalities at scintigraphy, bone scans in 214 patients with brucellosis and musculoskeletal symptoms were retrospectively analyzed. Bone scans were abnormal at a total of 319 sites in 196 patients (91.6%); 102 patients (47.7%) had multiple skeletal abnormalities. Plain radiographs were abnormal in 52 of 214 patients (24.3%). The sacroiliac joints were the most commonly affected site (142 patients [72.4%]); bilateral involvement of these joints occurred in 92 patients (46.9%). The sternoclavicular joints were affected in 32 patients (16.3%); costovertebral junctions, eight patients (4.1%); and symphysis pubis, three patients (1.5%). It is concluded that scintigraphy is sensitive in detection of skeletal brucellosis and should be performed when screening patients with brucellosis and musculoskeletal symptoms. PMID- 1924783 TI - Preoperative staging of esophageal cancer: comparison of endoscopic US and dynamic CT. AB - Fifty patients with esophageal cancer proved by means of biopsy underwent preoperative staging with endoscopic ultrasonography (US); in 42 of the patients, dynamic CT of the chest and abdomen was also performed. All results were compared with the findings at pathologic examination of resected specimens. In staging the depth of tumor growth, endoscopic US was significantly more accurate (46 of 50 tumors [92%]) than CT (25 of 42 tumors [60%]) (P less than .0003). In staging regional lymph nodes, it was more accurate (44 of 50 patients [88%]) than CT (31 of 42 patients [74%]), but this was not statistically significant. In staging distant metastases, however, CT was more accurate (38 of 42 patients [90%]) than endoscopic US (35 of 50 patients [70%]) (P less than .016). The highest concordance with surgical and pathologic findings in overall stage (36 of 42 tumors [86%]) occurred with the combined use of CT and endoscopic US, which was significantly more accurate than use of CT alone (27 of 42 tumors [64%]) (P less than .008). PMID- 1924784 TI - Preoperative staging of gastric cancer: comparison of endoscopic US and dynamic CT. AB - Fifty consecutive patients with gastric adenocarcinoma proved by means of biopsy underwent preoperative staging with endoscopic ultrasonography (US). Dynamic computed tomography (CT) of the chest and abdomen was performed before surgery in 33 of the patients. In all 50 patients, the TNM classification of the American Joint Committee on Cancer was used to compare the imaging findings with pathologic findings in specimens resected at surgery. When the depth of tumor penetration was evaluated, the findings at endoscopic US and those at pathologic examination were concordant in 46 of 50 patients (92%), and the findings at dynamic CT and those at pathologic examination, in 14 of 33 patients (42%) (P less than .00042). Evaluation of regional lymph node metastases showed a concordance of 78% with endoscopic US and 48% with dynamic CT (P less than .038). Overall determination of stage with both dynamic CT and endoscopic US showed a concordance of 73%, compared with a concordance of 45% for dynamic CT alone (P less than .028). PMID- 1924785 TI - Esophageal insufflation and videofluoroscopy for evaluation of esophageal speech in laryngectomy patients: clinical implications. AB - Esophageal speech proficiency in 75 laryngectomy patients was rated on a seven point scale by a speech therapist. Radiologic evaluation of the reconstructed pharyngoesophageal (PE) region during swallowing, attempted phonation, and phonation, by means of esophageal insufflation and barium-enhanced videofluoroscopy and spot radiography revealed the PE segment to be normal in 13 patients and hypotonic in 21. Hypertonicity or spasm of the PE segment was detected in 28 patients. Three patients had a postoperative stricture. Speech in 24 patients was fluent at the time of assessment; the remainder had negligible speech. Correlation between esophageal speech fluency and response at insufflation was highly positive. Esophageal insufflation, when combined with radiologic assessment, provides a reproducible method for accurate evaluation of the PE transition zone. Videofluoroscopy allowed good visualization of tracheoesophageal dynamics. Results indicated anatomic factors in the reconstructed PE region to profoundly affect the acquisition of esophageal speech. PMID- 1924786 TI - Segmental anatomy of the liver: a sonographic approach to the Couinaud nomenclature. AB - The authors developed a simplified description of the segmental anatomy of the liver on the basis of the Couinaud nomenclature. This approach was demonstrated with normal in vivo sonographic images and livers dissected in corresponding planes. The branches of the portal vein, which lead to the center of individual segments, are used as key landmarks in the determination of segmental location. The hepatic veins, ligaments, fissures, and gallbladder are used as external boundaries of the segments. PMID- 1924787 TI - MR imaging of liver metastases at 1.5 T: similar contrast discrimination with T1- and T2-weighted pulse sequences. AB - The authors evaluated soft-tissue contrast on spin-echo (SE) proton density weighted, SE T2-weighted, SE short-echo-time (TE) T1-weighted, and gradient-echo (GRE) images of 34 patients with known hepatic tumors who underwent high-field strength (1.5-T) magnetic resonance imaging. For solid liver tumors, the difference in the mean lesion-liver contrast-to-noise ratios (C/Ns) with T1- (GRE and SE) and T2-weighted pulse sequences was not statistically significant (P greater than .05). For nonsolid liver tumors, the T2-weighted images provided significantly greater (P less than .05) mean lesion-liver C/N than T1-weighted GRE images. Mean liver signal-to-noise ratio was significantly greater on T1 weighted GRE (P less than .0001) and T1-weighted SE (P less than .05) images than on T2- and proton density-weighted images. Qualitative analysis of T1-weighted (SE and GRE) images and proton density- plus T2-weighted images showed that lesion conspicuity was similar in 25 of 32 patients (78%). The results suggest that liver tumor imaging at high field strength can be performed with short-TE T1 weighted (SE or GRE) or conventional T2-weighted pulse sequences. PMID- 1924789 TI - Rectal carcinoma: staging at MR imaging with endorectal surface coil. Work in progress. AB - To increase the accuracy of local staging of rectal carcinomas at magnetic resonance (MR) imaging, the authors placed on endorectal coil mounted on a balloon in a position adjacent to the lesion. Use of such a local coil resulted in increased signal-to-noise ratio compared with use of a body coil; higher resolution images were obtained because the field of view was decreased. The depth of wall invasion by rectal carcinoma was correctly staged with endorectal MR imaging in 11 of 12 patients. In the detection of perirectal adenopathy, use of MR enabled correct identification of positive perirectal nodes in four of seven patients (57%). There were no false-positive diagnoses of perirectal adenopathy at MR. Endorectal MR imaging is an evolving and promising technique for the local staging of rectal carcinomas, but further studies are needed to demonstrate its efficacy. PMID- 1924788 TI - Perfluoroctylbromide as a gastrointestinal contrast agent for MR imaging: use with and without glucagon. AB - The utility of perfluoroctylbromide (PFOB) as a gastrointestinal contrast agent for magnetic resonance (MR) imaging was evaluated with MR examinations performed in 30 subjects (16 healthy volunteers and 14 patients). Transaxial T1-, proton density-, and T2-weighted MR images were acquired in each subject before and after the administration of PFOB. The healthy volunteers each underwent two sets of post-PFOB MR examinations, one before and one after glucagon administration. The degree of bowel marking, clarity of bowel-wall visualization, ability to distinguish bowel from adjacent parenchymal organs, and severity of phase encoding artifacts were independently analyzed by two reviewers. Oral administration of PFOB significantly (P less than .001) increased the percentage of bowel loops with low signal intensity. Subcutaneous administration of glucagon significantly (P less than .001) increased the clarity of bowel-wall visualization on post-PFOB MR studies. The severity of phase-encoding artifacts did not change substantially after administration of PFOB or glucagon. PMID- 1924790 TI - Hepatic hemangiomas: diagnosis with fusion of MR, CT, and Tc-99m-labeled red blood cell SPECT images. AB - A method of image analysis was developed for correlation of hemangiomas detected at computed tomography (CT) and/or magnetic resonance (MR) imaging with increased blood pool activity evident at single photon emission CT (SPECT) performed after labeling of red blood cells with technetium-99m. Image analysis was performed in 20 patients with 35 known hepatic hemangiomas. After section thickness and pixel sizes of the different studies were matched, intrinsic landmarks were chosen to identify anatomically corresponding locations. Regions of interest (ROIs) drawn on the CT and/or MR images were translated, rotated, and reprojected to match the areas of interest on the corresponding SPECT images by means of a two-dimensional polynomial-based warping algorithm. Analysis of ROIs on 30 SPECT-MR and 20 SPECT CT pairs of registered images provided absolute confirmation that 34 suspected hemangiomas identified on SPECT images correlated exactly with lesions seen on CT and/or MR images. Accuracy of fusion was within an average of 1.5 pixels +/- 0.8 (+/- 1 standard deviation). The technique enabled diagnostic confirmation of hemangiomas as small as 1.0 cm and proved useful for evaluating lesions located adjacent to intrahepatic vessels. PMID- 1924791 TI - Comparison of Kaopectate with barium for negative and positive enteric contrast at MR imaging. AB - In an evaluation of safe, inexpensive, orally administered contrast agents for use at magnetic resonance imaging, different concentrations of the clay agents kaolin-pectate and attapulgite were compared in an in vitro phantom by performing spin-echo imaging with variable echo times to estimate T2 relaxation time. Additional phantoms containing from 0% to 100% attapulgite or barium preparations were compared by using spin-echo and spoiled-gradient-echo techniques to estimate T1, T2, and T2* relaxation times. In vivo spin-echo and gradient-echo images were obtained of 10 healthy volunteers and of five patients with pancreatic disease after oral administration of 12-16 oz of attapulgite preparation. T1 and T2 relaxation times obtained with use of attapulgite were slightly lower than those obtained with kaolin-pectate at both 50% and 25% concentrations. Compared with barium, attapulgite had shorter T1, T2, and T2* relaxation times, and concentration-dependent relaxivity was greater by nearly an order of magnitude. All subjects were able to drink the attapulgite, and the only complaints were of bad taste and mildly loose stools. PMID- 1924793 TI - Aortic dissection: atypical patterns seen at MR imaging. AB - Aortic dissection is typically manifested by an intimal flap separating true and false lumens. Atypical patterns lacking an intimal flap can occur, however, and are less well recognized. In this study, the authors review their experience with atypical patterns at magnetic resonance (MR) imaging. They evaluated the T1 weighted and gradient-echo MR images of the entire aorta in 64 patients with aortic dissection. In nine patients (14%) aortic wall thickening was the only sign of dissection in the thorax. In three of these cases, an intimal flap was found in the abdominal aorta; the other six patients had no flap in any region of the aorta, and this led to false-negative angiographic results in three cases. Aortic wall thickening as an atypical sign of dissection was seen more frequently in acute (29%) than in chronic (7%) dissection and was seen in only patients without Marfan syndrome. Two patients with atypical acute dissection at initial examination developed a clearly identifiable intimal flap at follow-up. Aortic wall thickening may represent the only sign of aortic dissection. In some cases, imaging the entire aorta can enable recognition of dissection in atypical cases. PMID- 1924792 TI - Ovarian lesions: detection and characterization with gadolinium-enhanced MR imaging at 1.5 T. AB - Magnetic resonance (MR) imaging for detection and characterization of ovarian masses was assessed in 33 patients with a total of 60 lesions. Lesions were characterized prospectively as benign or malignant by using T2-weighted MR images and unenhanced and gadolinium-enhanced T1-weighted MR images. MR imaging findings were compared with results of surgical laparotomy performed for staging of lesions. When malignancy was suspected, staging with MR imaging was performed. MR imaging demonstrated 57 of 60 (95%) surgically proved ovarian masses (34 of 36 were benign, 23 of 24 were malignant). Five significant primary criteria and four ancillary criteria for malignancy were established. For all MR pulse sequences combined, characterization of either type of lesion was correct in 84% of cases (48 of 57) when the five primary criteria were used and 95% (54 of 57) were correct when the four ancillary criteria were added. With gadolinium-enhanced images, correct characterization of malignant lesions increased from 56% to 78% with use of the five primary criteria and from 83% to 100% with use of both sets of criteria. Malignancies were correctly staged with MR imaging in 12 of 16 patients. Staging accuracy was 63% with unenhanced images and 75% with the addition of enhanced images. PMID- 1924794 TI - Transvenous liver biopsy in critically ill patients: adequacy of tissue samples. AB - In a consecutive series of 33 patients (38 biopsies), the authors analyzed the pathologic specimens obtained with their relatively new transvenous biopsy method. From the point of view of establishing a useful pathologic diagnosis, the method proved worthwhile in the series of predominantly critically ill patients. A specific diagnosis or a later confirmatory tissue diagnosis was achieved in 18 patients, and a strong clinical correlation was achieved in 10 more. There were no complications from this repeatable, technically relatively simple, and safe procedure. PMID- 1924795 TI - MR anatomy of ventricular septal defect in double-outlet right ventricle with situs solitus and atrioventricular concordance. AB - Surgical treatment of patients with double-outlet right ventricle (DORV) depends on the spatial relation between the associated ventricular septal defect (VSD) and the arterial valves. This study was performed to refine the magnetic resonance (MR) imaging characteristics of VSD in DORV. Ten patients with DORV underwent MR imaging. Coronal, transverse, and oblique images were obtained with an electrocardiographic-gated multiple-section spin-echo technique. The transverse plane was the most valuable in defining the spatial relation of the VSD to the arterial valves. The site of fusion of the outlet septum with the VSD margin was diagnostically the most important feature in differentiating subaortic from subpulmonary VSD. The outlet septum fused with the anterior margin in subaortic VSD and the posterior margin in subpulmonary VSD; it was absent in doubly committed VSD. This study suggests that MR imaging can demonstrate the pertinent features of VSD and may be an indispensable adjunct to echocardiography in the preoperative evaluation of patients with DORV. PMID- 1924796 TI - Palmaz stent in atherosclerotic stenoses involving the ostia of the renal arteries: preliminary report of a multicenter study. AB - Palmaz balloon-expandable stents were placed in 28 hypertensive patients with atherosclerosis involving the ostia of the renal arteries. Stents were placed to treat elastic recoil immediately after conventional angioplasty in 20 patients and restenosis after percutaneous transluminal angioplasty in eight patients. Technical success (greater than 30% residual stenosis) was achieved in 27 patients. Complications occurred in five patients. At follow-up (1-25 months), hypertension was cured in three patients and improved in 15 patients, with a cumulative cure or improvement of 64% at 6 months. Of 14 patients with a serum creatinine level of 1.5 mg/dL (132.6 mumol/L) or greater before the placement of stents, five demonstrated improved renal function, five showed stabilization of their condition, and four demonstrated deterioration. Follow-up angiography (2-18 months) was performed in 18 patients. Restenosis was present in seven patients and was accompanied by a relapse of hypertension in only three patients. Of the other four patients with restenosis, two had no initial improvement and two had an initial response without a relapse of hypertension. In this preliminary study, renal stents were beneficial in many patients with poor results from conventional angioplasty for ostial atheroma. PMID- 1924797 TI - Peripheral arterial obstructions: analysis of patency 1 year after laser-assisted transluminal angioplasty. AB - Sixty-eight peripheral angioplasty procedures were augmented with direct argon laser energy in 63 non-consecutive patients. Technical success was achieved in 100% of femoropopliteal stenoses, 88% of femoropopliteal occlusions (mean length, 9 cm), and 71% of occluded iliac segments (mean length, 6 cm). In femoropopliteal arteries, the primary success rate was 83% (15 of 18) for occlusions longer than 7 cm and 92% (22 of 24) for occlusions 7 cm or shorter (P = .63). Complications included three thermal perforations and two emboli. The 1-year patency rate was 75% overall and 91% for femoropopliteal stenoses; iliac and femoropopliteal occlusions had patency rates of 79% and 60%, respectively. Disease severity was predictive of 1-year patency (85% for claudication vs 23% for limb-threatening ischemia; P = .0003), while distal run-off and femoropopliteal lesion length was not (P = .30 and .69, respectively). For patients with claudication who had femoropopliteal occlusions, a 1-year patency rate of 84% was obtained in short lesions versus 68% in long lesions (P = .36). For patients with limb-threatening ischemia, similar stratifications yielded patency rates of 21% and 33% (P = .38). PMID- 1924798 TI - Focal amyloidosis of the head and neck: evaluation with CT and MR imaging. AB - Localized amyloidosis of the head and neck was found retrospectively in the nasopharynx (n = 3) and orbit (n = 1) of four female patients (mean age, 32 years), three of whom had a prior history of antigenic stimulation. In all patients, computed tomography revealed a slightly high absorption and a relatively homogeneous, partially calcified mass. In the one patient who underwent magnetic resonance (MR) imaging, a distinctive loss of signal intensity was seen on the long repetition time/echo time sequence. This enhanced T2 relaxation may be due to (a) static or slowly fluctuating internal magnetic fields arising from adjacent amyloid protons held in relatively fixed positions within the beta-pleated sheet, resulting in quick phase dispersion; (b) chemical exchange and spin-spin interaction with adjacent water protons; and (c) diffusion through differences in diamagnetic susceptibility. This unusual appearance at MR imaging may improve the ability of radiologists to distinguish focal amyloidosis from many other diseases that affect the head and neck. PMID- 1924799 TI - Middle cerebral artery: determination of flow velocities with MR angiography. AB - A magnetic resonance (MR) angiographic technique for noninvasive measurement of flow velocities in the intracranial cerebral arteries was studied. Velocity measurements were made in a phantom and in the middle cerebral artery of six volunteers. Velocities were assessed in the volunteers before, during, and after finger movement. Average values for mean maximal velocities determined with MR angiography were 69.8 cm/sec before, 77.2 cm/sec during, and 69.6 cm/sec after finger movement. Correlations between values obtained with MR angiography and transcranial Doppler (TCD) sonography were r = .86 and P = .0001 for values obtained at rest and r = .84 and P = .0001 for values obtained during finger movement. The velocity increase during finger movement compared with that at rest was 11% for MR angiography and 11.3% for TCD sonography. Values measured with TCD sonography, however, were less than those measured with MR angiography (P = .001). The results show the feasibility of measuring flow velocities in intracranial arteries with MR angiography. PMID- 1924800 TI - Size and shape of the pituitary gland during pregnancy and post partum: measurement with MR imaging. AB - Cranial magnetic resonance (MR) imaging was performed in 38 pregnant and postpartum women and 30 nonpregnant age-matched control subjects to establish standards for pituitary gland size and shape during this period. Gland height and infundibulum width were measured on midline T1-weighted sagittal images. Gland convexity or concavity was graded qualitatively. Throughout pregnancy, gland height increased linearly by approximately 0.08 mm/wk. No gland exceeded 10 mm in height during pregnancy. Increases in gland convexity also correlated with progression of pregnancy. The largest glands were seen in the immediate postpartum period; during this period, five of 12 glands measured 10.0-11.8 mm. Beyond the first week post partum, glands rapidly returned to normal size, apparently regardless of the status of breast-feeding. The mean diameter of the infundibulum was 2.2 mm (range, 0.8-4.0 mm). The pituitary gland enlarges throughout pregnancy but should probably not exceed 10 mm during most of this period. Size of up to 12 mm may be acceptable immediately post partum. PMID- 1924801 TI - T1 and T2 relaxation time estimates in the normal human brain. AB - Magnetic resonance (MR) relaxation time constants T1 and T2 were estimated in frontal and occipital white matter, the caudate nucleus, and the thalamus nucleus in 79 healthy subjects aged 19-85 years. The in vivo estimates were obtained with 0.02-T and 0.8-MHz MR imaging. T1 values were estimated from a series of inversion-recovery images and T2 values from spin-echo images with a single section, single-echo technique. Although estimates were obtained from only one section, the investigated regions were distinguished from each other by the T1 values. With a polynomial regression test, the T1 data fit a cradle-shaped relation to age, with minimal values at ages 40-45 years. Sex and laterality did not influence the age-dependency results, but differences in the age-dependence curves for men and women were seen. The inclusion of 10 individuals with somatic disorders did not alter the findings. PMID- 1924802 TI - T1 and T2 in the cerebrum: correlation with age, gender, and demographic factors. AB - The authors measured the T1 and T2 of cerebral tissue in 164 volunteers aged 5-90 years and correlated T1 and T2 with age, gender, and various demographic variables. A weak correlation with statistical significance was found between age and T1 and T2 in white and gray matter structures. The T1 and T2 in the telencephalon increased by about 0.1% per year. No correlation of T1 or T2 with any other demographic, life-style, or medical factors was found. PMID- 1924803 TI - Complications of epidural anesthesia: MR appearance of abnormalities. AB - Eight patients with acquired intradural arachnoid abnormalities caused by epidural anesthesia were evaluated with magnetic resonance (MR) imaging (eight patients) and intraoperative ultrasound imaging (four patients). Subarachnoid cysts were found in the lower cervical and thoracic spine in six patients. Irregularity of the surface of the cord was noted in seven cases. Associated intramedullary cysts and myelomalacia were seen in two patients. Arachnoiditis was unsuspected clinically in four patients; findings at MR imaging first suggested the cause of the patients' symptoms. The underlying mechanism for the intradural and cord abnormalities in seven of the eight patients was a chemically induced arachnoiditis produced by the administration of epidural anesthesia; in the eight case, an infection introduced at the time of the epidural injection was the cause of the abnormalities. The authors postulate that the preservative agents in the vials of anesthetic may have been the causative factor of this inflammation in the majority of the cases. PMID- 1924804 TI - CT patterns of intracranial hemorrhage complicating thrombolytic therapy for acute myocardial infarction. AB - Computed tomographic (CT) patterns of intracranial hemorrhage (ICH) were determined in 1,696 patients undergoing thrombolytic therapy for acute myocardial infarction. ICH occurred at 33 sites in 0.77% of patients (n = 13). Thirty-six percent of hemorrhages (n = 12) were intraparenchymal, 33% (n = 11) were subdural, 24% (n = 8) were subarachnoid, and 6% (n = 2) were intraventricular. Eight-four percent (n = 26) of all nonventricular hemorrhages were supratentorial in location. The most common site of ICH was supratentorial and intraparenchymal (10 of 33). In 11 of the 13 patients with ICH, clinical symptoms occurred within 24 hours of the initiation of thrombolytic therapy. A fatal outcome resulted in three of the four patients who had clinical symptoms within 3.5 hours after beginning thrombolytic therapy. The CT findings of multiple intracranial bleeding sites, substantial mass effect with midline shift, and large-volume intraparenchymal hematomas were associated with increased mortality. ICH associated with thrombolytic therapy for acute myocardial infarction has a grave prognosis, with 62% of patients dying during hospitalization. PMID- 1924805 TI - Ossification of the fetal spine. AB - The neural arch ossification centers in the distal fetal spine were evaluated with ultrasound (US) during the second trimester of pregnancy in 239 fetuses. Ossification of the neural arch centers occurred in a predictable pattern and in a caudal direction. An additional vertebral level became ossified every 2-3 weeks from L-5 through S-5 after 16 weeks gestational age; by 22 weeks, S-2 was ossified in all fetuses studied. Radiographic and histologic correlation was performed in one fetus, and the method of establishing vertebral level with US proved accurate. In addition, the origin of the echoes at US corresponded to the histologic ossification centers. In 95% of the fetuses, S-1 was at the top of the iliac wing. Therefore, the level of ossification in the distal fetal spine could be rapidly assessed. Ossification to S-2 by 22 weeks, with a normal transverse configuration, normal overlying integument, and normal cranial structures, should lead to reassurance in excluding neural tube defects, except for distal sacral lesions. PMID- 1924806 TI - Color Doppler US imaging during pediatric neurosurgical and neuroradiologic procedures. AB - Experience with color Doppler imaging (CDI) during 16 pediatric intraoperative and one percutaneous neuro-radiologic procedures was reviewed to assess whether CDI increased the success rate or decreased the procedure time, thus contributing substantially to procedure performance. Intraoperative CDI was used to rapidly identify abnormal vessels or displacement of normal vessels and correlated with preoperative studies. In six cases (four vascular malformations, one mycotic aneurysm, and one hamartoma), surgical resection was altered on the basis of flow information obtained. In one case of percutaneous embolization of a Galenic malformation, CDI provided information contributing to the cessation of the procedure. In six cases (debulking of three gliomas, resection of one vascular malformation, and two biopsies of nonneoplastic conditions), information was added but did not alter the surgical approach. In the remaining four cases (three cerebrospinal fluid drainage procedures, one posterior fossa decompression), no additional information was obtained. Consultation among the ultrasound staff, neuroradiologists, and neurosurgeons before the operative procedure maximized the usefulness of CDI, thus aiding in the success of surgery. PMID- 1924807 TI - Intramedullary lesions of the pediatric spinal cord: correlation of findings from MR imaging, intraoperative sonography, surgery, and histologic study. AB - Findings of preoperative magnetic resonance (MR) imaging and radiologist-directed intraoperative sonography (IOS) were correlated with surgical and pathologic findings in 11 pediatric patients with intramedullary spinal cord lesions. There were seven gliomas and one each of primitive neuroectodermal tumor, venous vascular malformation, neuroenteric cyst, and active schistosomiasis. MR imaging provided discrete preoperative anatomic localization and excluded multicentric lesions but did not reliably distinguish between solid and cystic lesions. IOS helped (a) define the limits of intramedullary mass before the dura mater was opened and (b) differentiate cystic from solid components. The internal architecture of intramedullary lesions, as shown with MR imaging and sonography, was strikingly similar, allowing discrete correlative localization for biopsy or tissue resection. Gadolinium-enhanced MR imaging and IOS are complementary imaging techniques that should be used in concert for the evaluation and management of intramedullary lesions of the pediatric spinal cord. Both techniques display regions of cord abnormality, but neither definitively characterizes underlying tissue histology. PMID- 1924808 TI - Cerebellar dimensions in assessment of gestational age in neonates. AB - To determine whether cerebellar dimensions measured with cranial ultrasonography help assess gestational age in neonates, the authors measured the area, circumference, and vertical length of the vermis and the area, circumference, and maximum transverse width of the cerebellar body in 80 healthy neonates. These dimensions were correlated with the clinically assessed gestational age. All three measurements of the vermis and cerebellar body strongly correlated with gestational age. The area and circumference of the vermis were superior to the maximum transverse cerebellar width in prediction of gestational age. Multiple regression models made with a single vermis measurement along with either the cerebellar area or its circumference further improved gestational age prediction (r = .88; P less than .0001). The cerebellar dimensions also correlated strongly with clinically assessed gestational age in 13 neonates between 500 and 750 g birth weight, 18 neonates small for gestational age, and 12 neonates in whom clinical and obstetric assessments of gestational age were discrepant by more than 2 weeks. PMID- 1924809 TI - MR imaging of diffuse bone marrow replacement in pediatric patients with cancer. AB - In the magnetic resonance (MR) imaging examinations of three children with tumors (two neuroblastoma, one rhabdomyosarcoma) and three with leukemia, the marrow demonstrated a diffuse, uniform pattern of hypointensity on T1-weighted images and hyperintensity on T2-weighted images. The authors observed that this reversal ("flip-flop") of the usual MR characteristics of fatty marrow was seen in the epiphyses, metaphyses, and diaphyses. The purpose of this study was to establish the radiographic and clinicopathologic correlates of this MR finding on the basis of findings from plain radiographs, bone scans, and bone marrow aspirates. Plain radiographs and bone scans demonstrated either normal findings or changes limited to the metaphyses. In all patients, analysis of bone marrow aspirates demonstrated metastases. The authors concluded that even in the absence of evidence of discrete bone metastases on a plain radiograph or a bone scan, this diffuse and uniform "flip-flop" pattern reflects diffuse marrow replacement by tumor cells. PMID- 1924810 TI - Method for measuring three-dimensional motion with tagged MR imaging. AB - Recent methods of magnetic resonance imaging involve the placement of a grid of planes of saturation over the imaging plane; distortion of the grid corresponds to tissue displacement in two dimensions. An extension to this method that allows measurement of motion in the third dimension involves a second acquisition that tilts the grid, allowing analysis of motion normal to the imaging plane. A rotating phantom was used to verify the accuracy of the motion measurements, and the technique was applied to the heart wall and skeletal muscle. Phantom results show that the measure of z motion can be as accurate as that of x and y motion. Three-dimensional displacements of heart-wall and skeletal muscle are shown. With an accurate measure of three-dimensional motion, more complete analysis of heart wall motion and contraction is possible. PMID- 1924811 TI - GRASE (gradient- and spin-echo) MR imaging: a new fast clinical imaging technique. AB - A novel technique of magnetic resonance (MR) imaging, which combines gradient echo and spin-echo (GRASE) technique, accomplishes T2-weighted multisection imaging in drastically reduced imaging time, currently 24 times faster than spin echo imaging. The GRASE technique maintains contrast mechanisms, high spatial resolution, and image quality of spin-echo imaging and is compatible with clinical whole-body MR systems without modification of gradient hardware. Image acquisition time is 18 seconds for 11 multisection body images (2,000/80 [repetition time msec/echo time msec]) and 36 seconds for 22 brain images (4,000/104). With a combination of multiple Hahn spin echoes and short gradient echo trains, the GRASE technique overcomes several potential problems of echo planar imaging, including large chemical shift, image distortions, and signal loss from field inhomogeneity. Advantages of GRASE over the RARE (rapid acquisition with relaxation enhancement) technique include faster acquisition times and lower deposition of radio-frequency power in the body. Breath holding during 18-second GRASE imaging of the upper abdomen eliminates respiratory-motion artifacts in T2-weighted images. A major improvement in T2-weighted abdominal imaging is suggested. PMID- 1924812 TI - Device for facilitating lesion localization in breast biopsies. AB - To allow easier radiographic localization and pathologic correlation of occult lesions in breast biopsies, a specimen holder composed of two Plexiglas plates was devised. The specimen is compressed between the plates and radiographed. The lesion can be localized by inserting a 22-gauge needle through the appropriate hole in the bottom plate. Holes are centered within alpha numerically labeled squares on a grid created by grooves on the plates. The grooves allow the pathologist to excise only the tissue with the lesion. PMID- 1924813 TI - Mapping distribution of amobarbital sodium in the intracarotid Wada test with use of Tc-99m HMPAO with SPECT. PMID- 1924814 TI - Radiology residents' work hours and study habits. PMID- 1924815 TI - Spherical objects: elliptical shape of shadows at the periphery of radiographs. PMID- 1924816 TI - Conservative management of stage I and II breast cancer. PMID- 1924817 TI - Periodic mammographic follow-up of probably benign lesions. PMID- 1924818 TI - 77th scientific assembly and annual meeting: Radiological Society of North America. Chicago, December 1-6, 1991. Abstracts. PMID- 1924819 TI - Nurse fails to treat prisoner: civil rights action. PMID- 1924820 TI - Nurse changes testimony & notes: credibility issue. Case in point: Georgia Osteopathic Hosp. v. O'Neal (403 S.E. 2d 235--GA (1991)). PMID- 1924821 TI - Flame emanates from patient's throat: death results. Case in point: Schmidt v. Gibbs (807 S.W. 2d 928--AR (1991)). PMID- 1924822 TI - Is collection of urine sample an unreasonable search? PMID- 1924823 TI - Dr. refuses to treat pt. in active labor. Case in point: Burditt v. U. S. Dept. of Health & Human Serv. (932 F. 2d 1362--TX (1991)). PMID- 1924824 TI - Legal case briefs for nurses. MI.: nurses fail exam--terminated: unemployment compensation issue; CO.: Board seeks nurse's medical records: do nurses waive confidentiality? PMID- 1924825 TI - Did posey belt fail or was there negligence? Case in point: Keyes v. Tallahassee Mem. Reg. Med. Ctr. (579 So. 2d 201--FL (1991)). PMID- 1924826 TI - AIDS--II. PMID- 1924827 TI - Psychiatric diagnosis in HIV-spectrum disorders. PMID- 1924828 TI - Psychopharmacotherapy of psychiatric syndromes in asymptomatic and symptomatic HIV infection. AB - It is evident that human immunodeficiency virus (HIV) infection is one of the most serious public health issues in decades. HIV infection compromises cell mediated immunity which ultimately may result in the acquired immunodeficiency syndrome (AIDS). AIDS, to date, remains an incurable and progressively fatal disorder. HIV infection is spreading beyond the originally identified high prevalence groups of gay/bisexual males, intravenous drug abusers, and recipients of infected blood or blood products. Today, more and more heterosexual males, women, adolescents, and children have been infected with this lethal virus. This report addresses some of the psychiatric complications associated with HIV infection and discusses the diagnostic and clinical management challenges that clinicians must face as they deal with the increasing population of HIV-infected patients. Depression, anxiety, psychosis, delirium, and dementia are commonly encountered disorders associated with HIV spectrum disorders which must be accurately identified and can be effectively managed with psychopharmacological interventions. PMID- 1924829 TI - A model of a psychiatric intervention for AIDS patients. PMID- 1924830 TI - The family context of AIDS. PMID- 1924831 TI - Children, adolescents and AIDS. AB - HIV-1 and AIDS are emerging as significant problems for medical and mental health professionals working with children, adolescents, or women of child-bearing age. Aggressive medical care, and new research advances are allowing infected individuals to live longer. However, prevention remains the only way to save lives. Developmentally informed and culturally sensitive psychiatric input is needed to 1) facilitate coordinated care of children and mothers, 2) shape educational programs which can effect behavioral change, targeting children, adolescents, Latinos, and African-American women, and 3) work with children, their families, and their communities to combat stigma and secrecy. Although the obstacles often appear overwhelming, pediatric AIDS invites clinical and research involvement to prevent what cannot yet be cured. PMID- 1924832 TI - Treatment issues for African-Americans and Hispanics with AIDS. PMID- 1924833 TI - Bereavement in AIDS. PMID- 1924834 TI - AIDS and the health care professional: evolving attitudes and strategies to effect change. PMID- 1924836 TI - Major breakthrough in Tasmanian SIDS research. PMID- 1924835 TI - Parents help themselves. Interview by Margaret Atkin. PMID- 1924837 TI - Barriers to environmentally sound health care. PMID- 1924838 TI - The direction of clinical nursing. PMID- 1924839 TI - AIDS "hypotheticals". PMID- 1924840 TI - The pain of grief. PMID- 1924841 TI - Preparatory for relief work: a nurses' perspective. PMID- 1924842 TI - Preventive health. AB - This study examines the introduction of a program by the clinical nurse consultant to have nursing staff teach all women who agreed to do BSE during their admission to a gynaecological ward within a major teaching hospital. A questionnaire was distributed initially to gauge the women's interest in being taught BSE. When this showed almost unanimous support, a program was set up. Several months after the introduction of BSE teaching, a further questionnaire was distributed to gauge the effectiveness of the teaching program and to pinpoint any problem areas. The results were positive, and the program has now become part of the nurses' every day routine. PMID- 1924843 TI - A case report of dorsal pancreas agenesis diagnosed by MRI and ERCP. AB - We present a case of dorsal pancreas agenesis demonstrated by MR imaging. Careful observation with endoscopic retrograde cholangiopancreatography and MR imaging led to the precise diagnosis. PMID- 1924844 TI - MR imaging of gastrointestinal leiomyosarcoma. AB - Two cases of leiomyosarcoma, one in the esophagus and the other in the small intestine, underwent magnetic resonance imaging (MRI). Spin echo T1-weighted images of both leiomyosarcomas showed almost the same intensity as muscle. Spin echo T2-weighted images showed the tumors to be hyperintense compared with fat; however, the esophageal tumor was more hyperintense than the small intestinal one. The jejunal leiomyosarcoma had a central cavity on MRI and CT, suggesting that it was malignant. PMID- 1924845 TI - Functional brain studies with H2(15)O-PET: strategies and problems for approaching higher brain functions with H2(15)O-PET. AB - Activation study using H2(15)O and PET is promising as a noninvasive approach to higher brain functions in humans. However before reaching a more complex paradigm, many fundamental problems need to be solved. In this study, we investigated the following issues: (1) reproducibility of regional cerebral blood flow in the resting state as measured by this method, (2) effect of physiological stimulation on cerebral blood flow, and (3) identification of activated areas on anatomical structures. Our data suggest that relative CBF images and their paired subtraction are more suitable for tapping functional localization. Changes in rCBF in the association cortex for more complicated tasks are, in general, smaller than those in the primary cortex. Combined display of PET images with three-dimensional reconstructed brain surface MR images was the most reliable technique for anatomical identification of the activated site. PMID- 1924846 TI - Loss of echogenic lesion of focal fatty infiltration in fibrotic liver. AB - Five alcoholics with chronic liver disease showed focal low density areas of the liver that varied in distribution on computed tomography (CT) but no corresponding lesions on ultrasonography. The densities of these areas on CT were much lower than that of spleen. All the areas disappeared 2 days to 4 weeks after patients entered the hospital, suggesting that they were focal areas of fatty liver. Four patients had liver cirrhosis and one liver fibrosis. These observations may add further evidence to our previous finding that increased echogenecity of the liver produced by fatty infiltration is attenuated by complicating fibrosis. PMID- 1924847 TI - Venography under fluoroscopic monitoring by digital subtraction angiography apparatus. AB - We developed a new digital subtraction angiography (DSA) technique for venography of the legs. Satisfactory venograms were obtained by recording the venous images on videotape with on-line fluoroscopic monitoring followed by enhancement of the images by an image processor. PMID- 1924848 TI - Embolization of extensive facial arteriovenous malformation via the orbital branches of the ophthalmic artery. AB - Facial arteriovenous malformation (AVM) occasionally involves the orbit, and surgery for the orbital portion is complicated by its hypervascularity. We successfully embolized the orbital branches of the ophthalmic artery to decrease intraoperative bleeding of a facial AVM, sparing the ocular branches. There has been only one report dealing with embolization of the orbital branches of the ophthalmic artery. PMID- 1924849 TI - Cyclophosphamide 24 hours before or after total body irradiation: effects on lung and bone marrow. AB - Preparative regimens for bone marrow transplantation (BMT) use a sequence of drugs, such as cyclophosphamide, in combination with radiation. However, the optimum sequencing of the two agents that will maximize tumor cell kill and minimize normal tissue damage is unknown and controversial. The studies presented here were done in order to determine the effect of cyclophosphamide on bone marrow and lung damage in mice when given 24 h before or after total body irradiation (TBI). A range of single doses of TBI was given before or after a single sublethal dose of 180 mg/kg of cyclophosphamide. The bone marrow of all mice intended for lung damage assessment was reconstituted with 5 x 10(6) syngeneic bone marrow cells. Lung damage was assessed by breathing rate and lethality; bone marrow damage by lethality at 30 days. LD50 values for pneumonitis were obtained between 30 and 84 days after cyclophosphamide and radiation and between 80 and 180 days after radiation alone. Dose modifying factors were obtained as the ratio of LD50s for mice given only TBI compared to those for mice given cyclophosphamide and TBI. Cyclophosphamide enhanced radiation pneumonitis when given before or after TBI, giving DMFs of 1.4 and 1.2 (1.1-1.4, 95% c.l.) respectively. The effect of cyclophosphamide on radiation pneumonitis was drug dose-dependent. The LD50 for death from bone marrow damage was reduced when cyclophosphamide was given either before or after TBI but the effect was greater, i.e. the LD50 was lower when cyclophosphamide was given after TBI. These data show that cyclophosphamide given 24 h after TBI causes less lung damage but more bone marrow damage in this mouse model. PMID- 1924850 TI - Local tissue air ratio in an anatomic phantom for 60Co total body irradiation. AB - Tissue-air ratio (TAR), as the basic dosimetric function, is not ideally applicable to all important locations in total body irradiation (TBI) dosimetry because it generally refers to central ray measurements. We therefore introduced the local TAR which depends on the specific distribution of the scattering centres around the location of interest. Local TAR measurements were performed in an anatomic water phantom, produced by a sculptor, representing a patient during TBI in the real treatment position. A comparison has been made between TAR values, defined on the beam's ray at different locations in the anatomic phantom and cubic phantoms of different size. The local TAR values in the anatomic phantom, having more realistic outer surface curvatures, are lower by a few percent in most locations. We consider these values more accurate and better applicable to TBI conditions than those obtained in cubic water phantoms, even if the volume of the phantom is adapted to the particular side of the body. PMID- 1924851 TI - Dose fractionation and tumour repopulation in radiotherapy for bladder cancer. AB - Local control of the 77 transitional cell carcinoma of the bladder was analysed with respect to total dose after normalization for variations in fraction size and to overall treatment time. For the TCD50 of 63.3 Gy protraction of overall treatment time from 40 to 55 days average gave the decrease in local control rate from 50% to about 5%. The decrease in local tumour control with extension of overall treatment time likely reflects accelerated tumour repopulation during the treatment. To determine the time onset of the accelerated tumour clonogen repopulation, data taken from the literature were analysed. Results show that on average tumour clonogen repopulation in transitional cell cancer of the bladder accelerates after a lag period of about 5-6 weeks after the start of treatment and that a dose increment of 0.36 Gy per day is required to compensate for this repopulation. Such a dose increment is consistent with about 5-8 day clonogen doubling time. It suggests that overall treatment time is an important factor in the dose fractionation and protraction of time may have a significant impact on treatment outcome. Thus, radiotherapy for bladder cancer should be completed as soon as possible and total dose for high probability of local tumour control should consequently be delivered in more than 5 fractions per week. PMID- 1924852 TI - Fractionated thermochemotherapy in vivo of a C3H mouse mammary carcinoma. AB - The interaction between fractionated heat treatment and fractionated drug treatment with cyclophosphamide (CTX) was investigated in a transplantable C3H mouse mammary carcinoma inoculated into the hind leg of C3D2F1/Bom mice. A tumour core temperature of 43.5 +/- 0.1 degrees C was achieved by immersing the tumour bearing leg into a water bath thermostatically maintained at 43.7 +/- 0.1 degrees C. CTX was administered i.p. using the maximum tolerated dose (MTD) (LD 1%) for single fraction treatment (100 mg/kg) as the maximum fraction dose. For combined treatment CTX was given 15 min prior to heating. The endpoint was the time to reach a tumour volume of 5 times the volume at first treatment. Specific growth delay was used as effect parameter. In dose-effect experiments using total treatment time at 43.5 degrees C as dose parameter, drug enhancement ratio (DER) was determined as the ratio of the slope of the dose-effect curve for MTD of CTX plus heat to the slope of the curve for heat alone. In dose-effect experiments using total CTX dose as dose parameter, thermal enhancement ratio (TER) was determined as the ratio of the slope of the dose-effect curve for CTX plus 43.5 degrees C for 30 min to the slope of the curve for CTX alone. The regimens investigated were single fraction treatment and 3 and 5 fractions with time intervals of 3 and 5 days. For single fraction treatment DER was 1.4 +/- 0.1 and TER 2.3 +/- 0.2. The drug sensitization of the effect of heat treatment tended to increase with increasing number of fractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1924853 TI - Dosimetry and fluence measurements with a new irradiation arrangement for neutron capture therapy of tumours in mice. AB - Incorporation of 10B in human tumours treated with fast neutrons would increase the local dose in the tumour. In tissue the neutrons are thermalized mainly causing the neutron capture reaction 10B (n,a) 7Li. The dose enhancement can be calculated using the thermal neutron fluence measured by activation of gold foils in a phantom. At a phantom depth of 5 cm a dose enhancement of (0.056 +/- 0.0028)% for each microgram of 10B per gram of tissue was determined in the tumour. A therapeutic gain by this dose enhancement in fast neutron therapy should be examined for a solid tumour in a mouse. The feasibility for neutron capture therapy of tumours in mice depends on the distribution of the tumour dose and on the effective shielding of the bodies of the mice. Therefore, a special holding device for simultaneous irradiation of four tumours was developed. The dose distribution in the tumours and in the surrounding bodies of mice was measured with TLD-300 in a special mouse phantom. PMID- 1924854 TI - Interstitial irradiation for carcinoma of the tongue and floor of mouth: Royal Marsden Hospital Experience 1970-1986. AB - One hundred and forty nine patients with carcinoma of the tongue or floor of mouth were treated with interstitial irradiation (+/- external beam therapy) using caesium needles or iridium wires between 1970 and 1986. Multivariate analysis showed the main predictors of outcome to be tumour stage, site and histology. Caesium and iridium techniques gave similarly good local control rates of 90% at 5 years for T1 and T2 tumours when used as the standard departmental method. Local failure was shown to have a major impact on the risk of dying from disease and elective neck irradiation (ENI) conferred a favourable benefit on neck control and survival provided the primary site was controlled. Patients less than 40 years of age appeared to have an unfavourable prognosis. Radical irradiation including interstitial techniques gives excellent results in early oral cancer and is the treatment of choice for T2 tumours. We recommend elective neck irradiation in patients at high risk of developing lymph node metastases. PMID- 1924855 TI - Maxillary sinus carcinomas: natural history and results of postoperative radiotherapy. AB - Between 1969 and 1985, 73 patients with maxillary sinus cancers underwent surgical excision and postoperative radiotherapy. The clinical stage distribution by the AJC system was 3T1, 16T2, 32T3, and 22T4. Six patients had palpable lymphadenopathy at diagnosis. Surgery for the primary tumor consisted of partial or radical maxillectomy, and if disease stage indicated it, ipsilateral orbital exenteration. This was followed by radiation treatment delivered through a wedge pair or three-field technique. All but three patients received 50-60 Gy in 2 Gy fractions to an isodose line defining the target volume. Elective neck irradiation was not routinely given. Clinically involved nodes were treated with definitive radiotherapy (five patients) or combined treatment (one patient). Forty-five patients had no evidence of disease at the last follow-up. The 5-year relapse-free survival for the whole group was 51% The overall local control rate was 78%. Patients with larger tumors, particularly if they also had histological signs of nerve invasion, had a higher recurrence rate than others. The overall nodal recurrence rate without elective neck treatment was 38% for squamous and undifferentiated carcinoma, and only 5% for adenoid cystic carcinomas. Therefore, our current recommendation is to deliver elective nodal irradiation routinely to patients with squamous or undifferentiated carcinoma, except for those who have T1 lesions. Treatment complications were vision impairment, brain and bone necrosis, trismus, hearing loss, and pituitary insufficiency. The incidence of major side effects was determined by disease extent and treatment technique. Many technical refinements were introduced in order to limit the dose to normal tissues in an attempt to reduce the complication rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1924856 TI - Is it necessary to repeat quality control procedures for head and neck patients? AB - Using serial verification films for detection of localization errors and in vivo measurements of the delivered dose, a comparison was made of the information obtained from a single check on the first treatment session or from repeated checks in subsequent irradiations, leading to an assessment of the predictive value of a single check. A total number of 215 films and 261 entrance dose measurements have been performed on 34 fields for 10 head and neck patients. The patients are immobilized with individual plastic masks fixed on the couch and treated on a 6 MV linac, supplied with an automatic verification system excluding the couch parameters. The global results show Gaussian frequency distributions with standard deviations of 4 mm for port film measurements and 3.4% for the dose measurements. Large errors (greater than 5 mm displacement and greater than 4% deviation from the expected dose) have been detected in 16% in the cranio-caudal direction and 24% in the antero-posterior direction with port films and in 15% of the in vivo measurements. In order to identify the nature of the errors, which can be random or systematic, the first measurement is taken as the reference value and shows that consecutive measurements on the same field were reproducible with standard deviations of respectively 2.5 mm and 1.8%. This means that a large part of the spread of the global results can be explained by systematic errors in the treatment preparation chain. With the first check, 6 out of 10 systematic localization errors and 7 out of 7 systematic errors leading to erroneous dose delivery have been detected. Therefore, most of the systematic errors, which affect the overall quality of the treatment, can be identified with the first check. The four systematic localization errors, missed with the first film, were of rather limited size: only one of them showed a mean displacement larger than 7 mm. Because the first measurement is an acceptable indication of the overall quality of the treatment delivery, the authors propose a code of practice for checking the treatment quality at the patient level. PMID- 1924857 TI - The effect of customized beam shaping on normal tissue complications in radiation therapy of parotid gland tumors. AB - The impact of customized beam shaping was studied for five patients with parotid tumors treated with a paired wedged field technique. For each patient two plans were generated. The standard plan had unblocked portals with field sizes defined by the largest target contour found in any CT slice. In the second plan customized beam's eye view (BEV) designed blocks were added to both beams. The differences in the dose distributions between the two types of plans were evaluated using dose-volume histograms (DVH). As expected, the dose distribution within the target volume showed no difference. However, a considerable sparing of normal tissue was observed for the plans with customized blocks. The volume of unnecessary exposed normal tissue that received more than 90% of the prescribed dose, was reduced by a factor of about 4: from 165 to 44% on average, if the volume is expressed as a percentage of the target volume in each patient. In particular, the homolateral mandible showed a mean decrease of 21% of integral dose when blocks were used. Normal tissue complication probabilities (NTCP) were calculated. For a tumor dose of 70 Gy, the average bone necrosis probability was reduced from 8.4% (no blocks) to 4.1% (blocks). For other normal tissues such as nervous tissue, other soft tissues and bones a substantial reduction of integral dose was found for all patients when individual blocks were used. PMID- 1924858 TI - The factors to consider in decision-making concerning adjuvant therapy of cancer patients. PMID- 1924859 TI - Clonal variation of DNA repair in a human glioma cell line. AB - Clonal heterogeneity in response to ionizing radiation was found for a human glioma cell line, IN859. We have investigated the most sensitive clone, the most resistant clone and the parent line for differences in DNA repair fidelity using the method of plasmid reconstitution. Significant differences in repair fidelity were found between the two clones, and between the sensitive clone and the parent line. The resistant clone and the parent line showed the greater repair fidelity. A comparison of two different restriction enzymes, which cleave the plasmid with blunt or cohesive-ended double-strand breaks, did not reveal differences in repair fidelity. Equal numbers of plasmids were integrated in each cell line, but the sensitive clone showed a higher frequency of misrepair of cleaved plasmid. Misrepair was characterized by partial or complete loss of sequence at the site of plasmid cleavage. We conclude that the radiosensitive clone exhibits increased misrepair. PMID- 1924860 TI - Prognostic factors for local control in nasopharyngeal cancer (NPC): analysis by multivariate proportional hazard models. AB - Despite the development of meticulous radiation therapy techniques, the local control of the nasopharyngeal cancer (NPC) remains unsatisfactory. We examined retrospectively the clinicopathologic factors which have impact upon local recurrence-free survival (LRFS) of the 67 patients with NPC who had been irradiated greater than or equal to 40 Gy with curative intent from 1975 through 1988. Three-year LRFS rate was 63%. T stage, histology, the presence of accompanying lymphocytic infiltration, and the properness of radiation therapy had influence upon LRFS with a statistical significance. Multivariate proportional hazard models showed that T stage and pathology retained significance. Radiation therapy properness emerged as a third factor when only the patients irradiated greater than or equal to 60 Gy were included in the analysis. From these results, three groups with low, moderate, and high risk of shortened LRFS could be separated. This risk classification could contribute to the stratification criteria of future study for the improvement of local control by new modalities. PMID- 1924861 TI - Radiotherapy of midbrain and brainstem tumours in children. AB - From 1984 to 1987 in the First Radiotherapy Department in the Centre of Oncology in Warsaw, 11 children with midbrain (group I) and 14 with brainstem (group II) tumours were treated. In 4 cases diagnostic biopsy was performed and in 21 diagnosis was established by CT scan. All children were treated with megavoltage radiotherapy with a Co-60 unit. The initial radiotherapy treatment volume was determined from CT scan and was subsequently adapted to include whole brain or whole cranio-spinal axis, depending on the response to treatment. Improvement or stabilization of disease in 23/25 (92%) of cases was observed. Total survival, longer than 3 years in 14/25 (56%) was observed, while 9/11 (82%) survived greater than 3 years (NED) in group I, and in 4/14 (28%) in group II. Ninety two percent of living children have normal school life, with minimal or no neurological defects. PMID- 1924862 TI - The effect on minimum tumor dose of restricting target-dose inhomogeneity in optimized three-dimensional treatment of lung cancer. AB - An examination was made of the effect upon the minimum tumor dose of a limit placed on the variation of dose across target. If the required level of target dose uniformity is slightly relaxed, a substantial improvement in the minimum tumor dose might appear. It was conjectured that this effect could be seen with treatments optimally planned and evaluated in three-dimensions. A model of advanced carcinoma of the lung treated with a computer controlled accelerator was used to test this hypothesis. A mathematical program for optimizing beam weights was used to determine the largest minimum tumor dose possible. In the six cases tested, a minimum tumor dose of greater than 80 Gy could be delivered if a 20% inhomogeneity limit was accepted. The minimum tumor dose fell to the range 44-64 Gy when the inhomogeneity limit was tightened to 13-17%. The results imply a need to examine the choice of a required level of dose uniformity from the range of values suggested in the 2-dimensional planning literature. If a strict bound-on dose uniformity is preserved, mechanisms--such as formal optimization--which can reduce target dose inhomogeneity will be valuable. PMID- 1924863 TI - Dose to superficial node for patients with head and neck cancer treated with 6 MV and 60Co photons. AB - The superficial neck nodes in only 1 out of 7 patients with head and neck cancer studied received more than 90% of the prescribed dose when treated with opposed 6 MV photons. Beam spoilers placed upstream from the patient enhanced the dose to the superficial node at the expense of higher dose to the skin. PMID- 1924864 TI - Modification of a three-dimensional treatment planning system for the use of multi-leaf collimators in conformation radiotherapy. AB - The multi-leaf collimator of the DKFZ is designed as a low cost add-on device for conventional linear accelerators for radiotherapy. The technical specification of the computer controlled collimator is described briefly. A major limitation in the use of the wide capabilities of multi-leaf collimators in the clinic is still an appropriate treatment planning system. This paper describes treatment planning and dose calculation techniques for multi-leaf collimators and shows examples where the capabilities of the collimator are used extensively. PMID- 1924865 TI - Effect of backscatter on cell survival for a clinical electron beam. AB - Relative to homogeneous scattering conditions in tissue-like materials, a large increase in dose for clinical electron beams can occur upstream from high atomic number heterogeneities due to backscattered electrons. The degree of this dose increase is uncertain due to the unknown energy distribution of the backscattered electron fluence. Cell survival after irradiation was studied for Chinese hamster cells at the depth of maximum dose in a clinical 6 MeV electron beam under normal scattering conditions and with the addition of a lead backscatter. No significant difference in cell survival was found between the two geometries when the dose increase due to the backscattered electron fluence was approximated by the product of the measured ionization and the normal scattering stopping power ratio. PMID- 1924866 TI - A linear-quadratic model of cell survival considering both sublethal and potentially lethal radiation damage. AB - We assessed the dose-dependence of repair of potentially lethal damage in Chinese hamster ovary cells x-irradiated in vitro. The recovery ratio (RR) by which survival (SF) of the irradiated cells was enhanced increased exponentially with a linear and a quadratic component, namely xi and psi: RR = e xi D + psi D2. Survival of irradiated cells can thus be expressed by a combined linear-quadratic model considering four variable, namely alpha and beta for the capacity of the cells to accumulate sublethal damage, and xi and psi for their capacity to repair potentially lethal damage: SF = e(xi - alpha)D + (psi - beta)D2. PMID- 1924867 TI - Renal damage in mice after sequential cisplatin and irradiation: the influence of prior irradiation on platinum elimination. AB - Doses of 4-6 mg kg-1 c-DDP given 6 months before renal irradiation caused only a modest increase in functional radiation damage (DEF 1.1). These effects could be explained by additive toxicities and the damage was much less than when c-DDP was given 3-6 months after irradiation. Pharmacokinetic studies did not demonstrate any decrease in the rate of platinum elimination after previous low-dose renal irradiation. PMID- 1924868 TI - Evaluation of cell attachment matrix (CAM) coated plates for primary culture of human tumour biopsies. AB - Baker et al. [Cancer Res. 46: 1263-1274, 1986] developed an adhesive tumour cell culture system (ATCCS) using a culture surface coated with a cell attachment matrix (CAM). The ability of CAM-coated plates to support the growth of cells from human tumour biopsies has been evaluated. Successful growth was obtained in 9/22 samples (41%), but fibroblasts, rather than tumour cells, grew in the majority. Comparison of CAM with other surfaces showed that CAM was no better for establishing tumour cell growth than the presence of feeder cells or an alternative attachment factor vitronectin. PMID- 1924869 TI - Hypofractionation: lessons from complications. PMID- 1924870 TI - Case #9. Dentinogenesis imperfecta. PMID- 1924871 TI - Tobacco and periodontics. PMID- 1924872 TI - Working for uncle Sam. PMID- 1924873 TI - In the fields. Clinics provide dental treatment to 3.5 million nomadic farmworkers who prepare the land and harvest the crops that feed America. PMID- 1924874 TI - Miss Manners would be pleased. PMID- 1924875 TI - Renew and relearn skills. PMID- 1924876 TI - Protection goes both ways. PMID- 1924877 TI - Find better options to mandatory tests. PMID- 1924878 TI - Combined Doppler US-color-Doppler in diagnostic imaging. PMID- 1924879 TI - Diversified application of Doppler US as related to the different US and radiological problems. PMID- 1924880 TI - Combined Doppler US-color-Doppler: physical principles, techniques and hemodynamic considerations. PMID- 1924881 TI - Neck vessel anatomy by combined imaging procedures and Doppler US. PMID- 1924882 TI - Combined diagnostic imaging and Doppler US in carotid artery disease. PMID- 1924883 TI - Anatomy of splanchnic vessels by combined imaging procedures and Doppler US. PMID- 1924884 TI - Trauma, especially of the submandibular glands, causes release of epidermal growth factor into bloodstream in mice. AB - Submandibular glands in mice were traumatized by handling and then removed. Immunoreactive epidermal growth factor (EGF) in serum increased after 5 min and continued to increase, reaching at 1 h a peak of 50-fold normal in males and twice normal in females. If after traumatization the glands were repositioned with their blood supply intact, maximal increase of serum EGF at 1 h was 190-fold control values in males and 2-fold in females. In male mice, incision of abdominal wall skin led to a 15-fold increase of EGF in the serum; this rise was absent 3 days after sialoadenoectomy. After traumatization, repositioned submandibular glands lost 80% of their EGF; after the abdominal wall incision, only 30%. Following removal of submandibular glands, decrease of EGF level in serum was very slow: to 60% of the initial value after 3 days and to 40% after 10 days. By the HPLC characteristics, immunoreactive EGF in control serum and at its peak were indistinguishable. Urinary excretion of EGF was significantly elevated only when its serum level was 190-fold normal. We conclude that traumatized submandibular glands discharge into circulation a large part of their stored EGF. A similar but much less pronounced process takes place after abdominal skin incision. The presence of EGF in serum after its slow decline in sialoadenoectomized mice shows that a fraction of circulating EGF may recirculate prolonging its apparent half-life. PMID- 1924886 TI - A comparative study of the effects of neonatal androgenization and estrogenization on prolactin secretion in adult female rats. AB - Effects of neonatal androgenization (NA) and estrogenization (NE) were compared especially in terms of the prolactin (PRL) secretion in female rats. Twenty-four h after birth, a total of seven groups of newborn female rats were treated as follows. Three NA groups received a single s.c. injection of 10, 100 or 1000 micrograms of testosterone, respectively. Similarly, three NE groups received 1, 10 or 100 micrograms of estradiol-17 beta, respectively. The remaining one group was injected with oil vehicle only, and served as controls. At 8 weeks of age, animals were killed by rapid decapitation. PRL, estradiol and progesterone were measured in the plasma. Anterior pituitary (AP) was weighed, and AP PRL content was measured. NA and NE, at the highest doses, resulted in a similar degree of hyperprolactinemia and hyperestrogenemia showing an effect ratio of about 1:10. This ratio was, however, not true with the lower doses. Furthermore, there was no dose-dependency in the effect of NE on the plasma PRL and estradiol levels. In turn, plasma progesterone levels were dose-dependently decreased by both NA and NE. AP PRL content, expressed per AP, was significantly higher than control values in only NA (1000 micrograms) and NE (100 micrograms) groups. AP weight was increased by NA (1000 micrograms) but not by any NE treatment. These results indicate that NA and NE do not always exert similar effects on the PRL secretion or on several other related parameters. Therefore, aromatization of testosterone to estradiol does not appear to be the sole mechanism mediating the neuroendocrine consequences of NA. PMID- 1924885 TI - Vasoactive intestinal peptide fluctuates in human blood with a circadian rhythm. AB - The vasoactive intestinal peptide (VIP) may be radioimmunoassayed in systemic venous blood. The plasma concentrations of VIP were investigated in human blood according to a chronobiological design. The study documented a circadian rhythmicity in time-qualified concentrations of VIP. Accordingly, VIP may be ascribed to biological variables characterized by periodicity in their physiological attributes. The rhythmic physiology of VIP is, however, highly disturbed in its tonic and phasic properties during senescence. PMID- 1924887 TI - Isolation and characterization of a hemoglobin-derived opioid peptide from the human pituitary gland. AB - An opioid nonapeptide was isolated from fresh frozen human pituitaries. Its primary structure (Leu-Val-Tyr-Pro-Trp-Thr-Gln-Arg) was identical to fragment 32 40 of the beta-, delta-, gamma- and epsilon-chains of human hemoglobin. A larger peptide of about 4.5 kDa, which generated a fragment containing the nonapeptide on trypsin digestion, showed an amino acid composition similar to fragment 1-41 of the beta-chain of human hemoglobin. The nonapeptide interacted with mu-opioid receptors in rat brain homogenates using [3H]-(D-Ala2, MePhe3, Gly-ol5) enkephalin and with sigma-receptors using (+)-[3H]-3-(3-hydroxyphenyl)-N-1 (propyl)piperidine, respectively. The affinities for mu-opioid receptors were in the same range as those observed for the structurally related beta-casomorphins. However, the isolated peptide showed markedly higher affinity at sigma-binding sites when compared to the beta-casomorphins or other opioid peptides. The opioid potency of this peptide as determined in the guinea-pig ileum myenteric plexus muscle preparation, was significant but less than that observed for the beta casomorphins. PMID- 1924888 TI - Identification, characterization and release of GRP gene-associated peptides from the normal porcine and human gastro-intestinal tract. AB - Using a radioimmunoassay directed towards human proGRP (42-53) on acetic acid extracts, immunoreactivity was measured throughout the porcine GI-tract in concentrations that were parallel to those of GRP (gastrin-releasing peptide or 'mammalian bombesin'). Gel filtration and HPLC studies of human and porcine tissue extracts revealed that the immunoreactivity was mainly due to a peptide with a molecular size of 8-9 kDa. The peptide did not contain the GRP sequence, making it a major fragment of the GRP C-flanking part of proGRP. Furthermore, a peptide of similar size with proGRP (42-53) immunoreactivity was released from isolated, perfused preparations of porcine antral and non-antral stomach and pancreas in parallel with GRP in response to electrical stimulation of the vagus nerves. Our results suggest that a processing of preproGRP occurs in normal, adult human and porcine tissues, that is similar to that previously demonstrated in small cell lung carcinomas and human fetal lungs. The finding that the immunoreactive proGRP fragment is released from the tissues upon appropriate stimulation raises the question of a possible physiological role for proGRP products other than GRP. PMID- 1924889 TI - Ultrastructural localization of neuropeptide FF, a new neuropeptide in the brain and pituitary of rats. AB - The octapeptide FLFQPQRF-NH2 or neuropeptide FF ('F8Famide'; FMRFamide-like peptide'; 'morphine-modulating peptide') has been isolated from the bovine brain. In this study, the ultrastructural localization of neuropeptide FF-like immunoreactivity was examined with pre-embedding immuno-electron microscopy in the nucleus of the solitary tract and in the posterior lobe of the pituitary gland of an adult rat. Neuropeptide FF-like immunoreactivity was detected only in neuronal structures of the medial and commissural nuclei of the solitary tract and in the neurohypophysis. In the medulla, the peroxidase-antiperoxidase reaction product was localized in large (100 nm) dense-cored vesicles and in the cytoplasm of the neuronal perikarya, dendrites and axon terminals. In the labeled terminals, small (50 nm) clear vesicles rimmed with the peroxidase-antiperoxidase reaction product were seen. Synaptic contacts of labeled perikarya and dendrites with unlabeled axon terminals were observed. Labeled axon terminals formed contacts with unlabeled dendrites and perikarya. In the posterior lobe of the pituitary gland, neuropeptide FF-like immunoreactivity was localized in nerve terminals frequently associated with blood vessels. The results suggest that neuropeptide FF-like peptides are localized exclusively in neuronal structures and that they are synthesized in cell somata and released from axon terminals. In the brain, neuropeptide FF-like peptides may act as neuromodulators involved in the regulation of autonomic functions. The localization of neuropeptide FF-like immunoreactivity in the neurohypophysis suggests endocrine regulatory functions of these peptides. PMID- 1924890 TI - Pancreatic hormone response to neuropeptide Y (NPY) perifusion in vitro. AB - Available data on the effect of neuropeptide Y (NPY) on insulin release are conflicting and little data exist regarding the effect of NPY on glucagon secretion. The purpose of the present study, therefore, was to characterize the direct effect of NPY on the release of these pancreatic hormones and to examine the role of glucose on these interactions. Using a perifused mouse islet system, we found that NPY suppressed both basal and glucose-stimulated insulin secretion. Thus, basal insulin release assessed as mean integrated area under the curve/20 min (AUC/20 min) decreased from 1446 +/- 143 pg to 651 +/- 112 pg (P less than 0.05) with the addition of 2 x 10(-8) M NPY and the AUC/20 min for glucose stimulated insulin output decreased from 1973 +/- 248 pg to 1426 +/- 199 pg (P less than 0.05). In both cases, this inhibitory effect was followed after removing NPY by a stimulation of insulin secretion which was typical of a 'rebound off-response'. In contrast, NPY exerted a stimulatory effect on basal glucagon release and significantly reversed the suppressive effect of high glucose on glucagon output. The basal glucagon AUC/20 min increased from 212 +/- 103 pg to 579 +/- 316 pg (P less than 0.05), while glucagon secretion in the presence of 27.7 mM glucose increased from 75 +/- 26 pg to 255 +/- 28 pg (P less than 0.01). In conclusion, we have shown that the direct effect of NPY on the endocrine pancreas is to suppress insulin but stimulate glucagon secretion. These data are compatible with a role for NPY in the regulation of pancreatic hormone output. PMID- 1924891 TI - Interactions between oxytocin, glucagon and glucose in normal and streptozotocin induced diabetic rats. AB - Oxytocin has been suggested to have glucoregulatory functions in rats, man and other mammals. The hyperglycemic actions of oxytocin are believed to be mediated indirectly through changes in pancreatic function. The present study examined the interaction between glucose and oxytocin in normal and streptozotocin (STZ) induced diabetic rats, under basal conditions and after injections of oxytocin. Plasma glucose and endogenous oxytocin levels were significantly correlated in cannulated lactating rats (r = 0.44, P less than 0.01). To test the hypothesis that oxytocin was acting to elevate plasma glucose, adult male rats were injected with 10 micrograms/kg oxytocin and killed 60 min later. Oxytocin increased plasma glucose from 6.1 +/- 0.1 to 6.8 +/- 0.2 mM (P less than 0.05), and glucagon from 179 +/- 12 to 259 +/- 32 pg/ml (P less than 0.01, n = 18). There was no significant effect of oxytocin on plasma insulin, although the levels were increased by 30%. A lower dose (1 microgram/kg) of oxytocin had no significant effect on plasma glucose or glucagon. To eliminate putative local inhibitory effects of insulin on glucagon secretion, male rats were made diabetic by i.p. injection of 100 mg/kg STZ, which increased glucose to greater than 18 mM and glucagon to 249 +/- 25 pg/ml (P less than 0.05). In these rats, 10 micrograms/kg oxytocin failed to further increase plasma glucose, but caused a much greater increase in glucagon (to 828 +/- 248 pg/ml) and also increased plasma ACTH. A specific oxytocin analog, Thr4,Gly7-oxytocin, mimicked the effect of oxytocin on glucagon secretion in diabetic rats. The lower dose of oxytocin also increased glucagon levels (to 1300 +/- 250 pg/ml), but the effect was not significant. A 3 h i.v. infusion of 1 nmol/kg per h oxytocin in conscious male rats significantly increased glucagon levels by 30 min in normal and STZ-rats; levels returned to baseline by 30 min after stopping the infusion. Plasma glucose increased in the normal, but not STZ-rats. The relative magnitude of the increase in glucagon was identical for normal and diabetic rats, but the absolute levels of glucagon during the infusion were twice as high in the diabetics. To test whether hypoglycemia could elevate plasma levels of oxytocin, male rats were injected i.p. with insulin and killed from 15-180 min later. Plasma glucose levels dropped to less than 2.5 mM by 15 min. Oxytocin levels increased by 150-200% at 30 min; however, the effect was not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1924892 TI - Effect of cholecystokinin receptor antagonists, MK-329 and L-365,260, on cholecystokinin-induced acid secretion and histidine decarboxylase activity in the rat. AB - To elucidate the regulatory mechanism of acid secretion by cholecystokinin (CCK) in vivo, we compared the effects of CCK and gastrin on acid secretion and histidine decarboxylase (HDC) activity. We also examined the effects of MK-329, a specific antagonist for pancreatic-type CCK receptor, and L-365,260, a specific antagonist for gastrin-type CCK receptor, on the action of CCK. Graded doses of CCK or gastrin were intravenously infused into conscious rats with gastric fistula. Gastrin-17 I infusion up to 10 nmol/kg/h resulted in dose-related increases in acid secretion. CCK-8 infusion also caused an increase in acid secretion. However, it reached a peak with 0.3 nmol/kg/h CCK-8 and attenuated with higher concentrations of CCK-8. This attenuating effect of a higher dose of CCK was reversed by MK-329, but not by L-365,260. Both CCK and gastrin were potent in increasing fundic HDC activity, and the effect of CCK on HDC activity was significantly inhibited by L-365,260, but not by MK-329. Taken together, the present study suggests that CCK and gastrin stimulate histamine formation via a gastrin-type CCK receptor, and the attenuating action of CCK with higher concentrations on acid secretion in vivo is mediated by a pancreatic-type CCK receptor. PMID- 1924893 TI - TRH-enkephalin interactions in the amygdaloid complex during gastric stress ulcer formation in rats. AB - The formation of gastric stress ulcers was studied as a function of interactions between thyrotropin releasing hormone (TRH) and endogenous opioids in the central amygdalar nucleus (CEA) in rats. Bilateral microinjections of TRH (1 or 10 micrograms) into the CEA produced dose-related aggravations in cold restraint stress (CRS, 3 h at 4 degrees C)-induced gastric ulcer formation. Similar stress ulcer facilitating effects were also seen with intra-CEA injections of the opioid antagonists, naloxone (1 or 10 micrograms). On the other hand, the enkephalin analog, D-Ala2-metenkephalinamide (DAMEA, 1, 10 or 20 micrograms) produced dose dependent attenuations in gastric stress pathology, the effects being most marked with the latter two doses. Pretreatment of rats with intra-CEA naloxone (1 microgram) (a) antagonized the gastric cytoprotective effects of DAMEA (20 micrograms) and (b) further aggravated the ulcerogenic response of TRH (1 microgram), without influencing significantly the TRH (10 micrograms) effect. Further, when DAMEA (20 micrograms) was administered intra-CEA just after TRH (10 micrograms), the stress ulcer facilitating effects of the latter was neutralized. The results indicate that TRH-enkephalin interactions are possible at the level of the CEA during CRS-induced gastric ulcer formation. PMID- 1924894 TI - Centrally administered NPY stimulated gastric acid and pepsin secretion by a vagally mediated mechanism. AB - We investigated the possible roles of centrally administered neuropeptide Y (NPY) on gastric secretion, serum gastrin levels and gastric mucosal blood flow in anesthetized rats. Centrally administered NPY dose-dependently stimulated gastric acid and pepsin secretion. The stimulatory effect of intracerebroventricular administration of NPY was more potent than that of intracisternal administration. Centrally administered NPY also increased gastric secretion in the central noradrenaline depleted rats. In contrast, intravenously administered NPY had no influence on gastric secretion. These stimulatory effects were abolished by vagotomy or atropine pretreatment. The serum gastrin levels did not change after central NPY injection. Although intravenously administered NPY slightly increased gastric mucosal blood flow, centrally administered NPY slightly diminished gastric mucosal blood flow. These results indicate that centrally administered NPY markedly influences gastric functions in the rat. PMID- 1924895 TI - Calcitonin gene-related peptide and capsaicin inhibit the circular muscle of the guinea-pig ileum. AB - Calcitonin gene-related peptide (CGRP) is known to excite, through the release of acetylcholine, the circular muscle (CM) of the guinea-pig ileum in vitro. In the present experiments, the effect of rat CGRP was investigated on the CM of tetrodotoxin-treated, spontaneously active ileum preparations. CGRP (1-10 nM) caused concentration-dependent inhibition of both the amplitude and frequency of spontaneous CM contractions. Capsaicin (a sensory stimulant known to release CGRP from primary afferents) also inhibited CM activity. The effect of 1 microM capsaicin underwent rapid desensitization, indicating specific action on afferent structures, whereas a high concentration of the drug (33 microM) inhibited CM activity most probably on the smooth muscle itself. PMID- 1924896 TI - Marsupial possum neurotensin: a unique mammalian regulatory peptide exhibiting structural homology to the avian analogue. AB - Neurotensin has been isolated from small intestinal extracts of an Australian marsupial, the brush-tailed possum (Trichosurus vulpecula). The primary structure was determined as: pGlu-Leu-His-Val-Asn-Lys-Ala-Arg-Arg-Val-Tyr-Ile-Leu. When compared with bovine neurotensin, marsupial possum neurotensin exhibits four amino acid substitutions. His for Tyr3, Val for Glu4 and Ala for Pro7 are identical with those found in chicken neurotensin. In addition, substitution of Pro10 with Val is unique among all neurotensins sequenced to date. Marsupial possum neurotensin is therefore of unique primary structure, displaying most sequence homology with its avian counterpart. This neurotensin may thus resemble the phylogenetic precursor present at the time of divergence of primitive mammals and birds. PMID- 1924897 TI - Endothelin-mediated constriction of prenodal lymphatic vessels in the canine forelimb. AB - Endothelin is a 21 amino acid peptide which is produced by the vascular endothelium and is believed to be the mediator of endothelium-dependent vasoconstriction. In the current study we assessed the ability of synthetic human endothelin-1 to affect prenodal lymphatic vessel contractility in the canine forelimb. Intralymphatic infusion of endothelin at 1.09 x 10(-9), 1.09 x 10(-8) and 1.09 x 10(-7) M significantly constricted lymphatic vessels as evidenced by dose-dependent increases in lymphatic perfusion pressure. The increase in lymphatic perfusion pressure seen during intralymphatic infusion of endothelin at 1.09 x 10(-8) M during the intra-arterial infusion of phentolamine was not significantly different from that seen prior to phentolamine, indicating that endothelin-mediated lymphatic constriction is not alpha-receptor mediated. Intra arterial infusion of endothelin at three infusion rates significantly increased forelimb arterial, systemic and lymphatic perfusion pressures. The constriction seen when endothelin (1.09 x 10(-8) M) was infused intralymphatically in the intact lymphatic system was not significantly different from that observed when only the prenodal lymph vessel was perfused. This indicated that the lymph nodes and efferent lymph vessels do not contribute significantly to the lymphatic constriction produced by endothelin. These data are consistent with the hypothesis that endothelin may modulate lymphatic function under either normal or pathophysiological conditions. PMID- 1924898 TI - [Coronary transluminal angioplasty. A reality in Panama]. AB - This communication describes the first successful Transluminal Coronary Angioplasty performed in the Republic of Panama. The patient was a 77 year old man who developed post-infarction angina twenty days after an acute inferior myocardial infarction. He had new manifestations of ischemia of the posterior lateral left ventricular wall. Dilatation of a severe proximal lesion of a large right coronary artery, the culprit vessel, was accomplished without complications. PMID- 1924899 TI - [Type I lissencephaly syndrome. Clinical, neuroradiologic and electrographic analysis]. AB - A case with lissencephaly (agyria) syndrome is described. This brain development defect must be included in the differential diagnosis of all infants with delayed motor development and congenital malformations and convulsions, especially of the infantile spasms kind. It is important to consider chromosomal studies in each of them and to offer genetic counseling to the parents. PMID- 1924900 TI - [Hemifacial spasm]. AB - A patient with hemifacial spasm is presented and the surgical treatment discussed. The compression was located at the level of the vascular supply of the left facial nerve trunk. Through a left suboccipital retromastoid craneotomy a microscopic vascular decompression was performed with satisfactory results. PMID- 1924901 TI - [New dosage of heparin during cardiac surgery with extracorporeal circulation]. AB - We studied the effect of 4 mg/kg of heparine, measured with the activity cosgulation time (hemocron), in cardiac surgical patients operated with extracorporeal circulation. The basal TCA was 118 +/- 13 seg with this doses of heparine. The majority of the patients (83.33%) with 4 mg/kg of heparine had more than 450 seg in comparison with the number of patients (30%) who had more than 450 seg with 3 mg/kg of heparine. PMID- 1924902 TI - [Combined endoscopic percutaneous drainage and endoscopic biliary lithotripsy in the management of acute cholangitis. First experience in Panama]. AB - Two unusual cases of acute cholangitis are presented. One patient had a 3 cm. common duct stone successfully fragmented with an endoscopic mechanical lithotriptor. The other patient had a hemigastrectomy with a Billroth II anastomosis. A combined percutaneous--endoscopic approach was required to perform the sphincterotomy and remove the duct stones. The different treatment alternatives and the literature are discussed. PMID- 1924903 TI - [Hereditary angioedema. Review and presentation of 2 cases in a family]. AB - The clinical records of two patients (mother and son) who had hereditary angioedema of type 1 since childhood are studied. The angioedema was present in each case after trauma, they both had history of chronic allergic rhinitis and the son had of spastic bronchitis. In each of these two patients the level of C4 and CH50 was low, C3 was normal and C1 INH was absent. In a twin (bivitaline) brother and one mother's sister as well as in the son's father the level of C1 INH was normal. They were treated every time successfully with steroids and antiallergic medicine. PMID- 1924904 TI - [Privatization of the Gorgas commemorative laboratory]. PMID- 1924905 TI - [Prenatal diagnosis and management of a case of cardiac tumor]. AB - The cardiac tumors are very rare when diagnosed in the prenatal period. The authors report a typical case diagnosed in the 27 week of gestation by echocardiography. This is the first case reported in Panama. PMID- 1924906 TI - [Echocardiographic assessment of patients with sickle cell anemia]. AB - One hundred and sixty four (164) patients were evaluated. Sixty (60) with Sickle cell disease (SSHg.) and ninety seven (97) with Trait (ASHg.); seventeen (17) were normal control group. The study confirmed that the incidence of cardiomyopathy in Trait (ASHg.) is greater than reported by other clinical investigations. Cardiac arrhythmia, atrial fibrillation, premature ventricular contractions, bundle branch blocks, and T and ST modifications with sub epicardial isquemia were most significant electrocardiographics changes. The possibility of myocardial infarction in SS patients with low or normal hemoglobin is significant. M-Mode and 2-D echo, demonstrated similar end diastolic volumes in AS and SS patients in which cardiomyopathy were diagnosticated. Patients with cardiac failure, treated with cardiotonics, diuretics and ACE were compensated most frequently. To prevent hemosiderosis, antioxydant (alfatocoferol and Ubiquinones) were used with satisfactory response. PMID- 1924907 TI - [Radioventriculography during exercise in the diagnosis and management of patients with coronary disease]. AB - We describe the use of exercise radionucleide ventriculography in patients with different probabilities of suffering from ischemic coronary disease. The majority of patients with low probability demonstrated an increase of the ejection fraction and the ones with a high probability a reduction. We describe the utility of this test in the diagnosis, evaluation of the severity and management of patients with coronary disease. PMID- 1924908 TI - [Results of a questionnaire survey of the practice and organization of postoperative peridural analgesia at 461 anesthesia departments]. AB - In 1988, questionnaires were sent to 1225 departments of anesthesiology to evaluate the practice of postoperative epidural analgesia (EA) in the Federal Republic of Germany. The following problems were investigated. To what extent are anesthesiologists concerned with postoperative pain therapy? Does EA play a major role in this, in particular outside the intensive care setting? Who is allowed to administer epidural injections: anesthesiologists, other physicians or nurses? What kind of monitoring is used? What agents are used for epidural injections and what problems and complications have arisen? In all, 461 (38%) evaluable forms were returned. Most anesthesiologists said they were responsible for postoperative pain control. In 75.3% of the responding departments EA was used as a method of postoperative pain therapy, while in 24.7% the catheter was removed immediately after the operation, in most cases for fear of complications resulting from insufficient monitoring. In clinical practice, however, EA was the only major alternative to routine intermittent injections of opioids as needed. Some departments reported that they restricted postoperative EA to patients in the intensive care unit or in the recovery room because adequate monitoring was not feasible on the ordinary wards. EA was administered in 62.4% on ordinary wards. But in only 25.7% were trained nurses allowed to give epidural injections. Most responding departments (77%) preferred epidural use of opioids during intensive care, in most cases morphine or buprenorphine in combination with low dose local anesthetics, and 66.7% also favored epidural opioids on ordinary wards. PMID- 1924909 TI - [Peridural anesthesia using high volume prilocaine--success rate and patient acceptance. A prospective study of 630 anesthetized patients]. AB - In a prospective clinical study the follow-up course of 630 lumbar single-shot and continuous epidural anesthetics in young patients (average age 24.5 years) with 20-25 ml prilocaine 2% (epinephrine concentration 1:200,000) and 0.1 mg fentanyl was examined critically. The patients were interviewed postoperatively about this method of anesthesia. In 89% of cases the patients had been found suitable for surgery without any additional medication; 9% of the patients needed 0.1-0.15 mg fentanyl and 2.5-5 mg midazolam i.v. Only in 10/630 cases was supplementary anesthesia needed. During anesthesia a drop in blood pressure by 30% or more of the original value was recorded in 1.4% of patients; 5 patients had obvious simultaneous bradycardia. Nausea and vomiting were observed in 2.5% of cases; in 6 patients the level of peridural anesthesia was as high as T4-5. Postoperatively, 19% of the patients complained of discomfort in the area of the lumbar vertebral column. It subsided significantly 2 days after surgery; in 5.6% of cases patients had micturition disorder needing treatment. In 93% of cases the patients considered the method of anesthesia quite acceptable; in the same circumstances 96.5% said they would prefer epidural block to general anesthesia. The main reasons for this were the possibility of observing the surgical operation (26.8%) and the likelihood of speedy recovery on the same day (24.3%). Epidural block is preferred to any form of general anesthesia according to the experience we have gained in these young patients without essential concomitant diseases and with exact consideration to the contraindications for all operations distal of segments T9 and T10. PMID- 1924910 TI - [Is the plasma protein binding of lidocaine modified by the simultaneous administration of midazolam?]. AB - Perioperative antiarrhythmic therapy with lidocaine (bolus dosage 100 mg followed by infusion of 200 mg/h) was performed in 24 patients; 12 of them simultaneously received an intravenous injection of 10 mg midazolam with the bolus of lidocaine (group I: with midazolam; group II: without midazolam). Central venous blood samples were collected over a period of 1 h (1, 3, 5, 10, 20, 30, and 60 min after the bolus) to evaluate unbound and total (protein-bound + unbound) plasma concentrations of lidocaine, thus calculating plasma protein binding. One minute after intravenous administration of lidocaine peak plasma concentrations occurred: in group I 5.38 +/- 1.99 micrograms/ml (mean +/- SD), in group II 5.25 +/- 1.90. Up to 60 min there was only a gradual decrease in plasma concentrations in both groups. There was no significant difference between the two groups (group I: mean free concentration 0.67-0.80 micrograms/ml; mean total concentration 4.84 5.38 micrograms/ml; mean plasma protein binding 83%-86%; group II: 0.69-0.89 micrograms/ml; 4.62-5.25 micrograms/ml; 82%-85%). We draw the conclusion that midazolam administration is safe in patients undergoing antiarrhythmic therapy or regional anesthesia with lidocaine. PMID- 1924911 TI - Nephrotoxicity in humans by the ultratrace element germanium. AB - Acute renal failure (ARF) or renal dysfunction (RD) associated with germanium induced nephrotoxicity has been reported in 18 patients since 1982. In 2 of these cases the patients died of acute renal and cardiogenic failure. In 17 of 18 cases biopsies showed vacuolar degeneration in renal tubular epithelial cells in the absence of glomerular changes, without proteinuria or hematuria. Accumulated elemental Ge intake in 17 patients over a period of 4 to 36 months ranged between 16 and 328 g, or more than 100 to 2000 times the average estimated dietary intake of Ge for man (1.5 mg/d; range 0.40 to 3.40 mg/d). The biological half-life of Ge is 4.5 days for kidneys, the highest retention level of any organ. The mean concentration of Ge in healthy adult kidneys is 9.0 mg/kg wet weight. In 3 patients studied with Ge-induced RD or ARF, urinary Ge excretion was 9, 15, and 60 ng/mL, compared to greater than 5 ng/mL in healthy controls, and remained elevated even 12 months after discontinuing supplemental Ge intake. The mechanism for Ge-induced nephrotoxicity remains unknown, although the suspected cause is the inorganic Ge salts, such as germanium dioxide. Sufficient evidence for a role of organogermanium compounds, such as carboxyethyl germanium sesquioxide or citrate-lactate germanate, in Ge-induced nephrotoxicity remains lacking. The recent introduction of over-the-counter Ge "nutritional" supplements in some countries increases the risk of additional cases of Ge-induced nephrotoxicity, especially if appreciable levels of inorganic Ge salts are present and consumed for long periods (greater than 3 months) at levels above the average daily estimated dietary intake for Ge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1924912 TI - The jaundiced heart: evidence of blunted response to positive inotropic stimulation. AB - Obstructive jaundice has been known to cause severe hemodynamic disturbance. The present study was therefore designed to assess the cardiac involvement in jaundiced patients. The multiple-gated blood pool cardioscintigraphic studies were done in 9 jaundiced patients who had either cholestatic or obstructive jaundice (mean total bilirubin 29.30 +/- 3.30 mg/dL), and in 8 normal volunteers (total bilirubin less than 1 mg%). None of the patients had evidences of obvious cirrhosis, intrinisic heart disease, or septicemia. Following intravenous dobutamine there was comparable change of blood pressure and heart rate in both groups. However the response of left ventricular ejection fraction (LVEF) to dobutamine (10 micrograms/kg/min x 5 min) was strikingly blunted in the jaundiced patients as compared to that seen in the normal controls (3.56 +/- 0.9 vs. 12.7 +/- 2.2%, p less than 0.005). Our present data thus show that there is blunted myocardial contractile response to the inotropic stimulation in jaundiced patients. Such myocardial refractoriness to beta-1 stimulation may contribute to the susceptibility of jaundiced patients to postoperative shock and acute renal failure. PMID- 1924913 TI - Myoglobinuric acute renal failure following electrical injury. AB - Eight patients with acute renal failure (ARF) following electrical injury were studied. The mean area of cutaneous burns was 23 +/- 16% (range 6-60%) and extensive tissue necrosis with gangrene was uniformly present. Oliguria developed 9.3 +/- 7 h (range 3-24 h) after the injury in 7 patients (88%). Urinalysis revealed presence of myoglobin in 75% of the patients. The mean duration of oliguria among those who recovered was 16 +/- 6 days (range 11-23 days) and the mean interval between the onset of oliguria and recovery of renal function was 25 +/- 6 days (range 21-34 days). Four patients died. The cause of death was Klebsiella septicemia in 1, hyperkalemia associated with extensive myonecrosis in 2 patients, and uncertain in 1 patient. Our observations showed that myoglobinuric acute renal failure associated with electrical injury carries a high mortality. Early detection and aggressive management of hyperkalemia and sepsis are necessary to reduce mortality among these patients. PMID- 1924914 TI - "Quality of life" for patients with end-stage renal failure. AB - The assessment of health status and quality of life among chronically ill patients is an area of current scientific interest. This paper considers the utility of a short but comprehensive instrument to assess the quality of life for end-stage renal failure patients. the Spitzer QL-Index was completed by 8 nurses for all patients in the Wellington region currently being treated with home hemodialysis (n = 58); hospital hemodialysis (n = 13); and continuous ambulatory peritoneal dialysis (n = 37). Results indicated that home hemodialysis patients achieve the highest quality of life in comparison to the other two treatment modalities. It is concluded that the QL-Index has some discriminative validity for this patient population, and its use may contribute to informed decision making by both patients and doctors. PMID- 1924915 TI - Treatment of steroid-resistant renal allograft rejection with OKT-3 and plasmapheresis. AB - The murine monoclonal antibody (OKT-3) and plasmapheresis therapy were applied in combination to treat acute renal allograft rejection in 31 patients who were not responsive to conventional bolus steroid treatment. Six of them were living related but ABO incompatible; another 25 patients were ABO compatible (1 was from a cadaver, 7 were from living unrelated donors, and 17 were from living related donors). Of these 31 patients, 25 (80.65%) showed perfect improvement in their graft function. These 25 patients had a mean follow-up time of 8 months, and had mean creatinine values of 1.2 mg% (0.8-2.8 mg%). It is concluded that OKT-3 and plasmapheresis combination therapy is very effective in reversing steroid resistant rejections in high-risk patients such as ABO-incompatible cases. PMID- 1924917 TI - [Another ceramic-tooth seal: the Willi Geller technique]. PMID- 1924916 TI - Effect of Ringer infusion on ischemic acute renal failure: caution on interpreting the results of short-term studies. AB - The effect of a 4.5 mL/h Ringer infusion on the recovery from a unilateral 40-min renal artery occlusion was investigated in Sprague-Dawley rats. The inulin clearance measured in the experimental kidney 24 and 48 h after the insult in control animals that did not receive the Ringer infusion was 0.14 +/- 0.10 (mean +/- SE) and 0.11 +/- 0.05 mL/min, respectively. In animals that received 24 h of Ringer infusion begun at the time of the renal artery occlusion the inulin clearance was 0.81 +/- 0.07 mL/min, a value significantly higher than either of the control groups (p less than .05). If, however, the Ringer infusion was stopped at 24 h and the inulin clearance measured at 48 h, it had decreased significantly (0.27 +/- 0.09 mL/min) and was no longer greater than the control groups. Similarly, if the infusion was continued for 48 h there was no longer a significant difference between the inulin clearance (0.37 +/- 0.11), when compared with 48 h of no infusion (0.11 +/- 0.05). The histology of the different groups corresponded with the functional data. We conclude that 24 h of Ringer infusion leads to functional and histological protection when measured at 24 h; however, if measured at 48 h, protection is no longer evident. These studies suggest that caution should be exercised in extrapolating from the results of protective maneuvers in ischemic acute renal failure investigated by short-term studies. PMID- 1924918 TI - [Epilepsy. The approach to some questions]. PMID- 1924919 TI - [The prevalence of buprenorphine consumption in a sample of outpatient drug abusers]. AB - We studied 184 patients with DSM III-R diagnostic criteria for opioid dependence who attended the Sta. Eulalia's CAS (outpatients facility) during 18 months in order to measure the buprenorphine use. We collected the data from the patient's reports on the present buprenorphine use. The period prevalence was 79% (43.5% of them were occasional users and 35.5% habitual; whereas the point prevalence was 16.8% (6.5% occasional users and 10.3% habitual). The average of buprenorphine use was 6.1 +/- 9.9 months. Main method of consume is crushing the pill then dilute it and then injecting the solution e.v. The usual way of getting the substance is from illegal market (about 65% of patients get it in this way). About the third of our patients have been involved in the illegal traffic of in this drug anytime. From the data presented above we conclude that a more strict control of buprenorphine in highly recommended. PMID- 1924920 TI - [The isolation and identification of Mobiluncus curtisii and Mobiluncus mulieris in genital specimens]. AB - Amongst 1.202 genital samples studied, the microscopic exam revealed in 179 (14.8%) cases flora compatible with bacterial vaginitis. Of these 179 samples, Mobiluncus SP was observed in 35 (19.6%) using Gram staining and in 18 (10.1%) this microorganism was isolated in agar RLK and anaerobic atmosphere. Using biochemical characterization M. curtisii species was found more frequently (15 isolations) than M. mulieris (3 isolations). Chromatographic characterization permitted the diagnosis of the genus but not the differentiation of the species. Out of the 35 cases of Mobiluncus observed microscopically, 11 (31.4%) were afterwards isolated while in 7 occasions Mobiluncus growth was obtained without having been previously visualized using Gram staining. The percentage of Mobiluncus observed was different according to the species since 2 of the 3 M. mulieris while only 9 out of the 15 M. mulieris were visualized. PMID- 1924921 TI - [The successive presence of acute lymphoblastic leukemia, Hodgkin's disease and acute myeloblastic leukemia in a female patient]. AB - A case is presented of a female patient initially diagnosed of acute lymphoblastic leukemia who was treated achieving complete remission. Twenty six months later and while in remission of her leukemia, she presented an abdominal mass the histological study of which showed infiltration due to Hodgkin disease. She was treated with chemotherapy type MOPP and complete remission was achieved. Four months after completing treatment she presented pancytopenia in peripheral blood. A bone marrow study was performed observing a blastoid infiltration with morphological and cytochemical characteristics of acute non-lymphoblastic M-5 leukemia. The possible common origin of the three clinical pictures is discussed given the recent findings regarding the origin of Reed-Sternberg cell. PMID- 1924922 TI - [45,X/46, XYnf/47, XYnfYnf/46, X, dic (Ynf) (q12) mosaicism in a female patient with gonadal dysgenesis and the stigmata of Turner's syndrome]. AB - A 17-year-old girl was referred to us because of primary amenorrhea and features of Turner's Syndrome. The karyotype obtained from peripheral lymphocytes cultures was mos 45,X/46, XYnf/47, XYnfYnf/46, X, dic (Ynf) (q12). The karyotype of fibroblasts derived from cultures of both gonads was mos 45, X/46, XYnf/47, XYnfYnf. The Y chromosome was non-fluorescent in all the examined lines. We report here the clinical and cytogenetic findings in a patient with an unusual sex chromosome mosaicism. PMID- 1924923 TI - [Coronary disease after the radiotherapy of the mediastinum in Hodgkin's disease]. AB - A 32-year-old man with Hodgkin's disease presented an acute myocardial infarction following mediastinal irradiation. A complete occlusion at the level of the proximal segment of the right coronary artery and a moderate stenosis of the left circumflex coronary artery was demonstrated by selective coronary angiography. An inferior hypokinesia was seen by the ventricular angiography. We discuss the possible role of the mediastinal irradiation in the induction of coronary heart disease as well as the importance of an early diagnosis. PMID- 1924924 TI - [A study of the tobacco habit in a general hospital]. AB - Health professionals are the individuals with the greatest capacity to influence the population on smoking habit. Unfortunately, recent statistics, report that this professional group smoke as much if not more than the rest of the population, thus difficulting the reduction of this social problem. In order to evaluate smoking habit in our hospital, we presented a study on the prevalence and attitude of smoking habit in all the personnel working in our hospital. We were negatively surprised that after several public campaigns on the subject, the prevalence of smoking amongst the hospital personnel. PMID- 1924926 TI - [A patient with pain in the left hemithorax and dyspnea]. PMID- 1924925 TI - [Pleural cholesterol: a useful determination]. AB - The difference between exudates and transudates is the first question a clinician must solve when facing a pleural effusion. A great number of parameters have been tried without a definite efficacy of any of them. Cholesterol is an easy, useful determination for distinguishing exudates from transudates. In our series of 86 patients a cholesterol value of 50 mg/dl allowed us to correctly classify 94.2% of effusions. The ratio between pleural fluid cholesterol/serum cholesterol was more efficient because it permitted to correctly classify 97.7% of effusions, in one of those major groups which constitute the binomial exudate/transudate. PMID- 1924927 TI - [Focal motor crises in nonketotic hyperglycemic decompensation]. PMID- 1924928 TI - [Myocardial infarct, neurological, renal and obstetrical pathology in a 23-year old woman with antiphospholipid antibodies of family incidence]. PMID- 1924929 TI - [Cardiac tamponade as the first manifestation of a pulmonary neoplasm]. PMID- 1924930 TI - [The evaluation in primary care of blood theophylline in patients with chronic obstructive pulmonary disease]. PMID- 1924931 TI - [Churg-Strauss allergic granulomatous vasculitis: pulse therapy with cyclophosphamide as an alternative treatment]. PMID- 1924932 TI - [Hepatic abscess and abdominal echography]. PMID- 1924933 TI - [Empty sella turcica associated with diabetes insipidus. A report of a new case]. PMID- 1924934 TI - [Congestive heart failure as the form of presentation of mediastinal actinomycosis]. PMID- 1924935 TI - [Massive pleural effusion as the first manifestation of acute pancreatitis]. PMID- 1924936 TI - [Propantheline overdose. Anticholinergic poisoning]. PMID- 1924937 TI - [Dietary intake of a representative sample of the population of Val-de-Marne: I. Contribution of diet to energy supply]. AB - Dietary intakes and its nutritional value were assessed during a nutritional survey performed in a population living in a district in the Paris area (Val-de Marne). Data were obtained from 1108 subjects, aged 6 months to 97 years, randomly selected from the telephone directories of 12 of 47 towns and cities in the district. Dietary intake was evaluated in individual home interviews conducted by specialized dietitians, using the dietary history method. Age appears to be an important determining factor in variations in nutritional intake. Large differences exist between men and women for most types of food consumption. But the relative contribution of the main groups of food groups to the structure of energy intake is very similar in both sexes and virtually constant in the different age groups after the age of 6. PMID- 1924938 TI - [Dietary intake in a representative sample of the population of Val-de Marne: II. Supply of macronutrients]. AB - This paper describes an assessment of the nutritional value (carbohydrates, proteins, fats) of food intake studied in a population residing in the Val-de Marne district of the Paris region. Data were collected from 1,108 subjects, aged 6 months to 97 years, randomly selected from the public telephone directories of 12 of the 47 towns and cities in the district. Dietary intake was evaluated from individual home interviews by specialized dietitians, using the dietary history method. Age was shown to be a major determinant of macro nutrient intake (expressed in absolute value) in both sexes. The amount of food consumed differed between men and women. Expressed as a relative value of energy intake (after exclusion of alcohol-related calories), the proportion of different macronutrients was similar in all age groups, for both sexes, and was not in agreement with recommended dietary allowances: too high levels of fats and insufficient levels of carbohydrates, especially starch. PMID- 1924939 TI - [Dietary intake of a representative sample of the population of Val-de-Marne; III. Mineral and vitamin intake]. AB - Mineral and vitamin intakes were assessed among 1108 subjects, aged 6 months to 97 years in 12 of 47 towns and cities in the district of Val-de-Marne (Paris area), using the telephone directory as random sampling base. Micronutrients intake was evaluated by individual interviews at home by specialized dietitians (dietary history method). Mineral and vitamin intake was found to vary widely with age. In absolute value, overall mineral and vitamin dietary intakes was higher in men than in women (except for vitamin C). Conversely, the dietary density for mineral and vitamins was higher in females. For a large part of the studied population, it would appear difficult to satisfy recommended dietary allowances for many micronutrients (iron, zinc, vit. B1, B6, C, A et E). These results bring to light possible difficulties in covering certain mineral and vitamin requirements in the French population. PMID- 1924940 TI - [Development of a conversion table of dependence of the aged on home aide needs]. AB - Planning home help for geographical areas requires information on disabilities and required needs. This paper proposes a methodology to estimate the amount of help required. The analysis is based on survey data from three French regions: Ile-de-France, Languedoc-Roussillon and Basse-Normandie and from a team of experts. The total need, whether covered by professionals or by the patient's social network is considered for three aspects: Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and additional help resulting from home conditions. The required average number of hours per week varies from 49.9 for people confined to bed or chair, to 3.8 for people able to get out of their house without help (group 4). The need for IADL represents 44% of the total need for group 1 and 60% for group 4. Housing conditions generated an additional time representing 3 to 5% of total need, according to the group considered. The methodology allows to identified discrepancies between requirements and help provided by region and by disability group within each region. It appears to be a useful tool in planning home-help. PMID- 1924941 TI - [Hospitalization of foreign residents living abroad at the Assistance Publique- hospitals of Paris (1981-1988)]. AB - In 1988, 10,386 foreign patients living abroad were hospitalized in the public Hospitals of "Assistance Publique" in Paris. Specific statistical methods starting from an anonymous file of patients, made it possible to study these hospital stays in terms of patients for each year between 1981 and 1988. Several factors are described: the various origins of the hospitalized patients; the overall decrease in the number of hospitalized patients during the period taken into account, with a detailed analysis for certain nationalities; the comparatively higher rate of tumors and cardiovascular diseases; the distribution of patients by diseases and by geographical origin. These data are in keeping with those of a recent survey on morbidity carried out by the Department of Health. PMID- 1924943 TI - Smoking recidivism among an age cohort of men in Zutphen (The Netherlands): 1960 1985. AB - Current smoking decreased and former smoking increased among a cohort of originally middle-aged men in Zutphen during the period 1960-1985. Cohort analyses revealed two distinct advantages in comparison with the usual cross sectional analyses: inconsistent answers on never smoking could be eliminated, and former smokers resuming their habit could be traced. Recidivism of smoking increased strongly during the period 1977-1985. If recidivism of smoking affected younger cohorts as well, it could develop into an important health problem. PMID- 1924942 TI - [Coding problems in medical information in the framework of the medicalization of the hospital information system]. AB - The authors review the difficulties presented by the description of medical data, on the basis of the french experience with the programme to medicalize the hospital information system. They explain the different steps in preparing a hospital discharge abstract, and the difficulties presented by each one. They particularly stress the phase of hierarchization in choosing the principal diagnosis. They propose some solutions to improve data quality and an approach based on medical practice patterns. PMID- 1924944 TI - [Prognostic factors in hemorrhagic cerebrovascular accidents in a population register]. AB - Since 1985, cases of acute vascular cerebral diseases observed among the inhabitants of the city of Dijon have been systematically recorded: 88 cerebral haemorrhages were reported from 1985 to 1988. Twenty-five variables have been defined from antecedents, clinical and para-clinical data. Seven variables, were statistically associated with death at the end of the first month: age, severity of neurological palsy, meningeal syndrome, coma or comatose state, hyperglycemia and mass effect on CAT-scan. Using a step-down variable selection procedure, two prognostic factors were found: loss of consciousness and advanced age. PMID- 1924945 TI - [Exposure to the risk of traffic accidents, a fundamental epidemiological parameter, and one difficult to measure]. AB - This is a review of the literature dealing with exposure to the risk of traffic accidents. We present the principal definitions of this concept, the different measures of risk exposure, indicators of the risk of traffic accidents, and the advantages and disadvantages of the methods used for the collection of data. The validity of the measure of exposure to risk is analyzed as well. We conclude that while distance travelled is the principal measure of exposure to risk accepted by the research community, it is necessary to use a composite measure which also takes into account the risk associated with the driver. PMID- 1924946 TI - [Diffusion of information on medical causes of death: interview procedures and costs]. PMID- 1924947 TI - [The campaign against leprosy]. PMID- 1924948 TI - [Suicide mortality in Aquitaine 1986-1988]. PMID- 1924949 TI - [Morbidity in Belgium]. PMID- 1924950 TI - [Teaching epidemiology during medical studies in Poland]. PMID- 1924951 TI - [Acute myocardial infarct in persons over 70. The results and differential characteristics]. AB - Distinctive features of patients over 70 years with acute myocardial infarction (AMI) are studied. Between May 1988 and April 1989, 420 patients with AMI were admitted to our hospital; 118 of them (28.5%) were older than 70 years. In this group of patients, proportion of woman was higher (36 vs 16%, p less than 0.001), while incidence of smoking and hypercholesterolemia was lower (41 vs 64%, p less than 0.001; and 15 vs 29%, p less than 0.05). There was no differences in other risk factors, prior history of coronary heart disease (angina, AMI, coronary surgery), or general features of AMI (location, proportion of painless AMI, non-Q wave AMI, evolved AMI, initial admission to coronary care unit or general ward, time from the beginning of symptoms to admission, residual ejection fraction). The incidence of severe complications was superior between older patients: shock, 17 vs 7% (p less than 0.05); Killip class III/IV, 30 vs 13% (p less than 0.001); and fascicular blocks: 26 vs 16% (p less than 0.05). Hospital mortality was also higher in older patients, 25.5 vs 14% (p less than 0.01). No patients older than 70 years received fibrinolytic therapy, and only one underwent coronary artery surgery (22% and 15%, respectively, in younger patients). Coronary arteriography, exercise test, radionuclide ventriculography and Holter monitoring were also performed before discharge in a lesser proportion in older patients. We conclude that mortality and severe complications were higher between patients over 70 years with AMI. We think that mortality could be decreased by a more aggressive management in, at least, selected groups of older patients with AMI. PMID- 1924952 TI - [The effects of ticlopidine administration at low doses on the incidence of restenosis following percutaneous transluminal coronary angioplasty]. AB - The incidence of restenosis remains the same as initially reported (30%) and no therapeutic approach has reduced its appearance. Platelets-induced smooth muscle cell proliferation probably play a preponderant role in the pathogenesis of restenosis. The aim of this study was to evaluate the effects of ticlopidine (250 mg/day) on restenosis rate after single lesion coronary angioplasty. One hundred seventy nine consecutive patients were prospectively included in this study and were assigned to ticlopidine (group T, n = 91) or to a control group (n = 88) in an alternative fashion. Age (60 +/- 10 vs 58 +/- 9 years), gender (87% vs 87% male), treatment, coronary risk factors, lesion morphology, stenosis severity pre and postangioplasty, type of vessel, collateral circulation, and left ventricular ejection fraction, were similar in the T and control groups, respectively. Unstable angina was more frequently found in group T patients (81% vs 65%, p less than 0.01). A late angiographic follow-up (7 +/- 2 months after angioplasty) revealed restenosis (greater than 50% luminal narrowing) in 26 patients (28%) in group T and in 21 patients (24%) in the control group (NS). At that time, 88% and 98% of patients without restenosis vs 35% and 48% of patients with restenosis were asymptomatic in the T and control groups, respectively. An exercise test prior to the late control angiogram was abnormal (angina and/or ST segment depression) in 77% and 73% of patients with restenosis in T and control groups, respectively. Thus, in our experience, ticlopidine at a dosage of 250 mg/day was unable to reduce restenosis rate after single lesion coronary angioplasty. PMID- 1924953 TI - [Experience with a protocol of systematic postfibrinolysis angioplasty in acute myocardial infarct]. AB - Two hundred twenty one patients admitted for AMI in the CCU, and treated with systemic thrombolysis with streptokinase have been retrospectively analysed and divided in two groups: the first 98 patients (group A) were included in a research protocol: The following 123 patients (group B) represent the clinical application of thrombolytic therapy in our unit. In group A coronary arteriography in the first 48 hours (84 patients), and PTCA to the infarct related artery with significant stenosis (39 patients) were performed systematically. In group B, 54 patients had coronary arteriography PTCA was restricted to 12 patients with symptomatic ischemia. No significant differences in base line clinical parameters were detected between groups A and B. Total hospital mortality was 5% and similar in both groups. Reinfarction rate was greater in group A, 13% than in group B, 5%, but not significantly different. Reinfarction was related to PTCA (chi 2 test p less than 0.05). The incidence of post infarction angina was related to the existence of more than one diseased vessel. These data suggest that protocol PTCA post thrombolysis is not effective in reducing post infarction ischemia or mortality. PMID- 1924955 TI - [The surgical section of the bundle of Kent as an operative treatment of the Wolff-Parkinson-White syndrome: apropos a series of 82 operated cases]. AB - Eighty two patients diagnosed of the Wolff-Parkinson-White syndrome (WPW) underwent operation for the surgical section of the Kent-His bundle. In these cases, posteroseptal localization (PS) occurred in 32, left lateral (LL) in 25, right lateral (RL) in six, anteroseptal (AS) in one, posteroseptal and left lateral in 14, right and left posteroseptal in two, anteroseptal and left lateral in one, and left lateral and right and left posteroseptal in one. All of the patients presented an invalidating clinical of palpitations and/or loss of consciousness, and episodes of atrial fibrillation and/or reciprocal rhythm were registered in all cases. The mean anterograde refractory period in the accessory pathways was 244 +/- 60 msec, and the shortest RR in atrial fibrillation was 190 +/- 36 msec. A mitral commissurotomy was carried out in 3 patients during surgery, mitral prostheses were implanted in two, a double aorto-coronary bypass was made in three and an interventricular communication was closed in one. After a follow-up of 36 +/- 18 months, the surgical section of the Kent bundle was found to be effective in 77 out 82 patients (94%). (In 70 out of 77 cases, both anterograde and retrograde conduction were totally abolished and in seven out of 77 obtunded. All patients were asymptomatic during the follow-up period). In 5 out of 82 patients, surgical treatment was ineffective all five showed a PS Kent His and two presented a second Kent-His fascicle (LL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1924954 TI - [The local and systemic effects of intracoronary ergonovine in patients with normal and nonspastic coronary arteries. A comparison with the intravenous ergonovine test]. AB - Local and systemic effects of intracoronary (two bolus injections of 25 micrograms at 3-min intervals) ergonovine were determined in 60 patients with angiographic non-spastic normal coronary arteries and were compared with the most usual intravenous ergonovine dose to induce coronary artery spasm (incremental doses of 50, 100 and 200 micrograms at 3-min intervals). The mean diameter of the vessels was reduced by 15% after selective injections (baseline 2.38 +/- 0.7; after intracoronary ergonovine 2.02 +/- 0.6 mm; p less than 0.001) and no significant changes were induced in the heart rate (before 80 +/- 15; after 79 +/ 15 beats/min) and systolic aortic pressure (before 147 +/- 27; after 149 +/- 28 mmHg). Following intravenous administration, the mean coronary diameter decreased by 20% (1.90 +/- 0.6 mm; p less than 0.01 vs intracoronary dose) and the heart rate diminished slightly (76 +/- 12 beats/min; p less than 0.01). Nevertheless, the systolic aortic pressure did increase by 16% (171 +/- 28 mmHg; p less than 0.001). No major complications were observed and the appearance of side effects was minimal. Thus, the intracoronary delivery route, at the applied dosage, induces lesser vasoconstriction than usual intravenous administration, and systemic effects, such as hypertension, are avoided. PMID- 1924956 TI - [Aortic valve replacement by a pulmonary homograft]. AB - Minor experience still exists in our country with regard to the use of valve homografts in cardiac surgery. Only a few implantations have been performed in cases of right ventricular outflow tract reconstruction in addition to our own experience in cases of infective endocarditis of the aortic valve. We present a case of aortic valve replacement by using an antibiotic-sterilized fresh pulmonary valve autograft. The case is described and the possible advantages of the use of pulmonary allografts in the aortic position are discussed. PMID- 1924957 TI - [A cholesterol embolism following coronary angioplasty. A case report]. AB - Cholesterol embolism is a rare but serious complication of heart catheterization. We report a patient in whom cholesterol embolization syndrome developed after coronary angioplasty complicated by an acute myocardial infarction which was treated with streptokinase and heparin. The clinical outcome was satisfactory. Cholesterol embolism occurrence might have been precipitated in this patient by thrombolytic and anticoagulant therapy. PMID- 1924958 TI - [The angiographic diagnosis of the connection of the persistent left vena cava superior to the left atrium by the absence of the roof of the coronary sinus in a child with a Holmes' heart]. AB - We describe a patient with angiographic findings of a left superior persistent vena cava draining in the left atrium with absence of the coronary sinus' roof and coexisting with Holmes' heart. The diagnosis can be made by selective angiography in the left atrium, pulmonary vein or at the left superior vena cava. We want to emphasize the importance of knowing this sort of anomaly before surgical treatment. PMID- 1924959 TI - [A solitary intracardiac metastasis in the left atrium from a pulmonary carcinoma]. AB - Cardiac metastases are the most common cause of neoplastic disease of the heart. Usually the metastases involve the pericardium and/or myocardium but rarely they form intracavitary masses. We report a patient with a lung cancer and solitary left atrial intracardiac metastases. General features of cardiac metastases and the differential diagnosis of left intra-atrial masses are discussed. PMID- 1924960 TI - [A primary epithelioid hemangioendothelioma localized in the pulmonary valve]. AB - A case of epithelioid haemangioendothelioma sited at pulmonary valve, with an excrescence growing invading pulmonary artery troncus and its principal branches, in a 56-year-old woman is reported. The evolutive behavior simulated some clinical situations which made difficult the diagnosis: a mild-moderate pulmonary stenosis, a general syndrome, and, finally, an acute pulmonary thromboembolism that carried to an aggressive management which conducted to the entity diagnosis. PMID- 1924961 TI - [The transcutaneous treatment of superficial thrombophlebitis with the exogenous nitric oxide donor: nitroglycerin]. AB - Nitroglycerin (glyceryl trinitrate) is a substance that is metabolized to nitric oxide in the cell. Its action is not dependent of the endothelium derived nitric oxide, but imitates those of this biological mediator. We thought that nitroglycerin should have the same in vivo actions as the endogenous nitric oxide in vitro has. We report and discuss the first patient with superficial thrombophlebitis successfully treated with transdermal nitroglycerin. PMID- 1924962 TI - [Isolated congenital diverticulum of the left ventricle]. PMID- 1924963 TI - Isolation of 203mercury-induced metallothionein in rat kidney by direct connection of HPLC to a beta radioactivity detector. AB - Rat kidney 203Hg-induced metallothionein (HgMT) was separated on a high performance liquid chromatograph equipped with a gel permeation column and an on line beta radioactivity detector, in order to obtain the simultaneous measurements of renal MT by UV detection and MT-associated 203Hg by a beta radioactivity detector. Metallothionein was separated in three major species by both UV detection at 254 nm and 203Hg detection, probably due to the presence of mercury and copper. A standard curve was prepared which demonstrated excellent linear correlation between the integrated HgMT peaks area and the quantity of HgMT injected into the column. In contrast to the results with the gel permeation column above mentioned, rat kidney HgMT was separated in four peaks by reversed phase height performance liquid chromatography. PMID- 1924964 TI - Propionyl-CoA synthetase in mammary gland and liver of cows. AB - Propionyl-CoA synthetase of liver and mammary gland from calf and midlactation cow was investigated. No activity of this enzyme was detected in calf mammary gland, but it was detected in calf liver. Propionyl-CoA synthetase was found in both, liver and mammary gland of the cow, although mammary gland activity was about 25% of that found in liver. The effects of pH and temperature on enzyme activity and stability were also investigated in crude extracts of liver and mammary gland tissues. The results suggest a different behaviour of the enzyme from both origins. Kinetic studies of the enzyme were also carried out, showing differences, depending on the organ, in the apparent substrate KM values. PMID- 1924965 TI - Effect of DTNB on rat intestinal galactose transport in vivo. AB - The effect of the non-penetrating reagent of -SH groups: acid 5,5'-dithiobis (2 nitrobenzoic), (DTNB), on 1 mM galactose absorption in rat intestine in vivo has been studied. DTNB inhibits sugar absorption in about 35%, which is due to an action on the mediated transport component, but without affecting the diffusional passive one. Consequently it does not modify galactose absorption in the presence of 0.5 mM phlorizin or that of the non-transportable sugar 2-deoxy-glucose. Galactose transport inhibition appears after a not longer than 5 min preexposure period and it remains constant at least up to 30 min. The inhibitory effect does not vary between 0.1 and 1 mM DTNB and it reverses completely with 0.5 mM dithioerythritol. Protection by excess of substrate has not been observed. Results show that DTNB affects sulfhydryl groups very probably located at the luminal side and related to the proteins of the cotransport system. PMID- 1924966 TI - Cadmium induction of metallothioneins in several dogfish organs. AB - Dogfish Scyliorhinus canicula were exposed to 50 mg/l Cd for 4 days for inducing metallothionein synthesis. Spleen, pancreas, kidney and gonads were dissected out and metallothionein presence was checked by means of gel filtration chromatography in Sephadex G-75 and sodium dodecyl sulphate polyacrylamide electrophoresis. In pancreas and kidney, a cadmium-binding protein with spectroscopical and electrophoretic properties similar to those of dogfish liver metallothionein was found. In the other organs, the existence of an analogue protein but at very low concentrations is feasible. PMID- 1924967 TI - Effect of different MCT/LCT ratios on protein synthesis in injured rats fed parenterally. AB - The effect of the lipidic composition of the diet on the proteic synthesis of the male Sprague-Dawley rats fed parenterally for four days has been studied. All animals received identical nitrogen and caloric intake, but the ratio of medium to long-chain triglycerides (MCT/LCT) varied: group 1, control (0/100); group 2 (30/70); group 3 (50/50) and group 4 (70/30). Hepatic and jejunal protein synthesis were determined with L-(1-14C)-leucine. In groups 1, 3 and 4 muscle protein synthesis was measured with L-(3,4-3H)-phenylalanine. In liver, there were no significant differences in the fractional synthesis rate among the groups. In jejunum, the control group showed a higher fractional synthesis rate with statistically significant differences among the groups. In muscle, group 3 presented the highest fractional synthesis rate with statistically significant differences (p less than 0.05). PMID- 1924968 TI - Influence of lithium and exercise on serum levels of copper and zinc in rats. AB - The variations in serum levels of Cu and Zn induced by exercise in rats undergoing Li therapy are determined. The results show that exercise until exhaustion leads to a reduction in the Li concentration, which is more pronounced in rats subjected to training (to 50% maximum capacity) in the week before the test. The serum levels of Zn and Cu increased significantly with exhaustion in untrained rats, while there were no significant alterations in trained rats, except for serum Zn in those not treated with Li. The modifications in serum induced by exhaustion are lower in rats treated with Li. It is likely that Li and exercise have opposite effects on the tissue distribution of the two ions studied. PMID- 1924969 TI - [The diagnostic value and therapeutic perspectives of monoclonal antibodies in bronchopulmonary cancer]. AB - Monoclonal antibodies (AcM) have opened up new perspectives in the study of cancer. The production of murine AcM has been well described in the past. The characterisation of the antigen which they recognise and their in vitro and in vivo biological properties has led to their use in diagnosis and in due course to therapeutic possibilities. The specificity of AcM "vis a vis" certain molecules or tumour associated antigens enables their utilisation for diagnosis and their widespread use for the labelling of tumour markers. AcM may in difficult cases be more accurate in specifying the histological type of a bronchopulmonary or pleural tumour; by coupling the antibody to a radio isotope and injecting it into the circulation. This enables the detection of tumours in vivo by immunoscintigraphy. The numerous problems linked to the technique and above to biology of AcM limits its clinical value in assessing the degree of extension either locally or regionally of bronchopulmonary tumours. The therapeutic applications are at this stage experimental and above all studies have shown the limits of AcM used alone or coupled to a radio isotope, a toxin or a drug. The limits of the technique are linked to numerous factors, such as accessibility of the antigen site, the heterogeneity of tumour markers and non specific fixation and immunogenicity of the AcM. The experimental clinical stage should be continued in order to define the most effective utilisation of AcM in therapy which will doubtless be complementary to other forms of treatment. PMID- 1924970 TI - [Bradykinin and asthma]. AB - Bradykinin and related kinins formed in tissues and fluids during inflammation, exert many physiological effects mediated by two receptor subtypes: B1 and B2. The involvement of kinins in bronchial asthma has been speculated in numerous clinicals reports. The effects of bradykinin on airways have been studied in vivo and in vitro in animals and humans, but its mode of action remains uncertain. The recent availability of selective B2 antagonists could be of help in defining more precisely kinins in the various aspects of asthma. PMID- 1924971 TI - [Bronchopulmonary dysplasia]. AB - Bronchopulmonary dysplasia (BPD) is one of the most serious complications of neonatal intensive care. This chronic lung disease usually follows early pulmonary injuries. Surfactant defect, oxygen toxicity and barotrauma are three major factors leading to diffuse alveolar and bronchiolar damage, first step of BPD. BPD usually appears in preterm infants and correlates with degree of prematurity and the severity of neonatal distress syndrome. Infants with BPD frequently have poor outcome; the mortality rate is near 30%. The long-term survival prognosis is uncertain with a risk of bronchopathy in adulthood. Until date, current management of BDP is unsuccessful. New strategies are required to prevent neonatal respiratory distress syndrome and decrease its severity. PMID- 1924972 TI - [Maximal ventilatory pressure through the mouth in adults: normal values and explanatory variables]. AB - Mouth pressure measured during maximal inspiratory or expiratory efforts depends on the force exerted by ventilatory muscles. Normal values and anthropometric factors accounting for maximal inspiratory and expiratory pressures (MIP, MEP) are not fully agreed upon to date. We measured MIP and MEP in 253 normal subjects (135 females and 118 males, age 15-59 years) using a digital transducer (163 Sibelmed). All subjects had normal forced vital capacity (FVC) and one second forced expiratory volume (FEV1). Sex, age, height and weight were recorded for all subjects and were entered as independent variables in computation of linear multiple regressions with MEP or MIP the dependent variables. MEP and MIP were greater in males than in females (p less than 0.01) with MIP lower than MEP in both sexes (p less than 0.01). In both males and females, FVC and FEV1 depend on age and height (p less than 0.01). In the entire group, we found a correlation of MIP in females and MEP in males with age (p less than 0.01) and of both MIP and MEP in females with weight (p less than 0.01). However, in subjects aged 20-59 years, there was no significant dependence of MIP and MEP on age, and when the weight of subjects was normal (n = 170), MIP and MEP were independent of weight. We conclude that in adults aged 20-59 years and with normal weight, maximal ventilatory pressures depend solely on sex. In this subgroup mean (+/- SD) values of MEP and MIP were 111 +/- 25 cmH2O and 79 +/- 19 cmH2O respectively in females and 192 +/- 42 cmH2O and 117 +/- 25 cmH2O in males. PMID- 1924973 TI - [The contribution of effort tests in the evaluation of factors related to dyspnea in pneumonology]. AB - Forty nine patients suffering from respiratory disorders underwent an exercise test carried out on a bicycle ergometer (n = 45) or by walking rapidly on flat or inclined ground (n = 4). The respiratory restrictions on effort were correlated with a degree of dyspnoea (stages 1 to 4) established by a questionnaire. The analysis of the effort test had consequences of practical importance: in effect, in this study, nearly half the patients benefited from advice orientated in particular towards the level of activity which would be suitable for them, and to reduction in their weight. PMID- 1924974 TI - [Cheese-washer's disease. A current stable form of extrinsic allergic alveolitis in a rural setting]. AB - Inhalation of organic particles (bacteria, fungi or animal proteins) by sensitized subjects is known to induce extrinsic allergic alveolitis (EAA). The most frequent type of EAA and the best known in rural environment is farmer's lung disease. Nevertheless a rarer form is also to be considered in rural environment: cheesewasher's disease. Here we report 4 cases of cheesewasher's disease, who all presented with relevant aspects of the disease: diversity of antigens involved, prophylaxis problems, severity of the disease, rapidity of onset, reversibility and importance of history in the diagnosis. Penicillium casei usually is the responsible antigen, and precipitating antibodies against these moulds, but against other moulds such as Aspergillus, Circinomucor circilloides, Fusarium as well, can be detected in the patient's serum. Thus, in a rural environment, a respiratory symptomatology suggestive of EAA should lead to thorough search for antigens and cheesewasher's disease should be considered. Among the many other diagnostic tests, precipitin determinations are cheap and non invasive and can be very useful in the diagnostic approach. PMID- 1924975 TI - [The usefulness of systematic follow-up of tuberculosis for the diagnosis of relapse in French Polynesia between 1971 and 1984]. AB - Standard chemotherapy for one year was proposed for the treatment of tuberculous patients in French Polynesia between 1971 and 1978, and for nine months with the addition of pyrazinamide from 1979 to 1984. After treatment, the patients were followed up systematically for a period of 5 years. The aim of this study was to evaluate the value of the follow up measures to detect relapses. Of 1,065 patients treated between 1971 and 1984 at the centre for the control of tuberculosis 35 (3%) presented with a relapse, of whom 30 were confirmed either by bacteriological examination or histological examination. The level of relapse seen was not linked to age, sex, nor type of treatment received (one year or nine months). However, the level of relapse in non compliant patients to the initial treatment (7%) was significantly greater than those observed in patients who were totally compliant (2%) (p less than 0.0001). Of the 35 relapses 9 (26%) were discovered during routine follow up visits, of whom 8 were detected during the first year. The median delay separating apparent recovery from relapse was 8 months. 28 patients (80%) presented with symptoms suggestive of a relapse. Over 5 years 5773 consultations were carried out, which meant 642 consultations to detect one relapse. The authors suggest that in French Polynesia a systematic follow up limited to one year after apparent cure should be adequate. PMID- 1924976 TI - [Which compressor should be used to deliver pentamidine aerosols with the Respirgard II?]. AB - Prophylaxis against pneumonia due to Pneumocystis carinii is most often carried out using pentamidine administered as an aerosol. For reasons both of comfort and cost this technique should be developed at home or at least in an extra-hospital environment. Using the Respirgard II as the nebuliser of reference this requires a compressor. We have assessed four different compressors and compared these to pressurised oxygen used in a hospital environment. During the course of nebulisation with a pentamidine aerosol two physical factors may coincide to limit their efficacy. First the deposition of some of the particles on the walls of the apparatus and secondly the production of a particle size which is incompatible with alveolar deposition. This study showed that according to the source of compressed air: 1) the fraction of the pentamidine solution found in an aerosol at the mouthpiece varies from 29 to 62%; 2) the fraction of the aerosol whose particle size is suitable for alveolar deposition (1 to 3 microns) varies from 35 to 48%. The product of these two fractions enables an assessment of the efficiency of each apparatus: 14 to 24% of the pentamidine solution may be deposited at the alveolar level. In addition to this efficiency the duration of the session (from 25 to 50 minutes) for each machine should be taken into consideration when considering the choice of the compressor to be coupled with the Respirgard II in order to improve the comfort and therefore the compliance to the treatment. PMID- 1924977 TI - [Cough and bronchial obstruction induced by citric acid in smokers, occasional smokers and non-smokers]. AB - We have studied cough and bronchial constriction induced by inhaling citric acid in 15 smokers with baseline airflow obstruction, in 13 occasional smokers and 13 non smokers. The threshold for cough was significantly higher in occasional smokers in relation to smokers and non smokers. Citric acid produced the same degree of bronchial constriction at the same time in smokers and occasional smokers: the maximum fall in forced expired volume (FEV1-VEMS) was recorded five seconds after inhalation of the citric acid (dose threshold) and there was no significant difference between the two groups. In the non smokers, the maximum fall in VEMS was recorded twenty seconds after inhalation of the citric acid and was significantly less in relation to that of the smokers and occasional smokers. In the smokers the degree of smoking could influence the fall of VEMS (% predicted). Cough and bronchial constriction after the inhalation of citric acid are probably related to different physiological mechanisms and are linked to the history of smoking. PMID- 1924978 TI - [Non-Hodgkin's lymphoma disclosed by an intrabronchial tumor. Apropos of a case]. AB - Non Hodgkin's lymphoma (LNH) presenting as a localised tumour is exceptional and nearly always appears during the course of disseminated disease. We report a case where the primary disease was an endobronchial tumour and the entire clinical picture related to pulmonary symptoms. A 70 year old lady was found to have a left sided pulmonary opacity following a cough with minimal expectoration and accompanied by chest pains and dyspnoea. The chest abnormality progressed for 3 years 9 months before an endobronchial tumour was discovered at bronchoscopy in the left upper lobe and from which a biopsy revealed an LNH with small cells of low degree of malignancy. In addition there was splenomegaly and an infiltration of bone marrow by the lymphomatous process which was evidence of a disseminated form of LNH. To our knowledge our observation is an extremely rare case where an endobronchial tumour revealed a non Hodgkins lymphoma. PMID- 1924979 TI - [Filarial eosinophilic lung. Apropos of a case]. AB - Pulmonary eosinophilia due to filariasis is a form of filarial infection which is frequent in endemic zones but very much rarer in Europe where it is always "imported". In this case report the authors specify the clinical characteristics and pathophysiology of this disease. PMID- 1924980 TI - [Pleural empyema and ruptured subdiaphragmatic abscess]. AB - The authors report a case of a ruptured right subphrenic abscess causing a diffuse peritonitis complicating a chronic empyema. The authors recommend active treatment of purulent pleurisies, particularly when they are associated with a bronchopleural fistula. PMID- 1924981 TI - [Remission of malignant pleural mesothelioma using high-dose cisplatin in monochemotherapy]. AB - The authors report a case of a malignant mesothelioma of the left main pleura diagnosed by thoracoscopy and treated by pleural talcage followed with four courses of chemotherapy using cisplatin in a dose of 40 mgms/m2 from days 1 to 5 resulting in a near complete remission for one year. Following a review of the literature the authors analyse the potential value of chemotherapy in this type of tumour whose treatment up to the present time has been particularly disappointing. PMID- 1924982 TI - [Pulmonary actinomycosis. Apropos of a case]. AB - The authors report a case of pseudo-tumoral thoracic actinomycosis with lysis of a rib in a young man who was a heavy smoker and drinker. This observation is an opportunity to review the usual difficulties of diagnosis in patients with this rare disease occurring most often in a patient who is debilitated with important disease in the teeth and gingival margins. The standard treatment is penicillin G, which leads to a cure within one month. PMID- 1924983 TI - [Does the "Revue des Maladies Respiratoires" concern itself with the French speaking world? Toward an alinguistic and non-polemic solution]. PMID- 1924984 TI - [Asthma and betaxolol eye-wash]. PMID- 1924985 TI - [Evaluation of D-dimer levels in obliterating arteriopathies]. AB - A research has been carried out for the evaluation of D-dimer serum levels by the ELISA technique at 1:200 and 1:500 dilution in 30 male patients suffering from chronic obliterating arteriopathy of the lower limbs at second and third stage of the disease and in a homogeneous control group for number, sex and age. The value difference between the two groups, for both dilutions, seems to be highly significant with higher levels in the arteriopathic patients. The extent of D dimer levels has shown an obvious correlation in respect to the entity of the arteriopathy. It has been also observed a significant correlation between the D dimer and LDL levels in the arteriopathic patients. The usefulness of such a parameter in order to prevent trophic lesions in the obliterating arteriopathy is emphasized for the possibility of establishing an early and prolonged thrombolytic therapy. PMID- 1924986 TI - [Intrahepatic cholestasis in hyperthyroidism]. AB - Three cases of cholestatic liver disease related to hyperthyroidism are reported. Features indicative of a role of the endocrine disease in the pathogenesis of the cholestatic syndrome were the appearance of liver damage in temporal relation with the clinical onset of thyroid hyperfunction and its disappearance with the amelioration of the hyperthyroidism; the absence of congestive heart failure and of infectious, toxic or obstructive agents of liver damage; the pathological and biochemical findings of intrahepatic cholestasis. Hyperthyroidism can be rarely complicated by a severe cholestatic syndrome that may dominate the clinical presentation and course. PMID- 1924987 TI - [Myocardial involvement in rhabdomyolysis caused by acute heroin intoxication]. AB - It is well known that heroin overdose may cause rhabdomyolysis. Sometimes a myocardial involvement complicates its course. We report a case of heroin intoxication followed by rhabdomyolysis associated with myocardial injury, with symptoms, laboratory findings, ECG and echocardiography features of non-Q wave infarction. However, a 201 Tl myocardial scintigraphy, performed after patient discharging, did not show any abnormality. We think that heroin has a direct myotoxic effect on both myocardium and skeletal muscle. Yet we cannot exclude that hypoxia, acidosis, vasoconstrictive substances released by muscle necrosis, or hypersensitivity reactions associated with heroin or some of its adulterants are involved in myocardial injury. PMID- 1924988 TI - [Lymphoma of the bladder. Description of 2 cases and review of the literature]. AB - Two case reports and review of the literature. The authors describe one case of primary lymphoma and one case of secondary lymphoma of the bladder. They evaluate the differences, underline the rarity of the primitive type and make a review of the literature. PMID- 1924989 TI - [Alcoholic hepatopathy, deficiency pathology and serum transaminases. Presentation of 2 clinical cases]. AB - The authors describe two cases of Vit B1 and B6 deficiency in alcoholics with malnutrition. In the first case serum levels of AST and ALT, initially below norm became higher after Vit B1 and Vit B6 intake; the second, with AST and ALT above norm in previous months, had AST and ALT with normal activity during the disease. The authors suggest that normal activity of AST and ALT during alcoholic hepatopathy could be related to a depletion of Vit B1 and Vit B6. PMID- 1924990 TI - Diabetes and gastrointestinal motor activity. AB - The gastrointestinal tract is frequently involved by diabetes, especially when automatic neuropathy is present. Hollow viscera motor activity is especially effected; in particular, gastric and small bowel function may be severely impaired, due to gastroparesis and dysmotility, although motility of the entire gut may be abnormal. The present review focus on the various aspects of abnormal motility of single digestive viscera in diabetic patients. PMID- 1924991 TI - [IgA nephropathy. A frequent disease in the Mediterranean area]. AB - Primary IgA nephropathy (IgAN) is a worldwide disease characterized by the recurrence or macroscopic hematuria episodes followed by continuous or intermittent microscopic hematuria. This disease is more frequent in men than in women and the prevalence is higher in the Asian and European areas than Australia and North-America. However the prevalence of IgA is strictly correlated with the biopsy policy and health screening urinary tests. The renal biopsy implicates the diagnostic and prognostic aspects since various histological degrees of renal lesions show different behaviour of the renal function. Even though the disease is progressive in a minority of patients various investigators have attempted treatment with various drugs. Corticosteroids seem to have effect on the course of IgAN in those patients with heavy proteinuria or nephrotic syndrome and normal renal function. Since Berger's original report the immunological mechanisms implicated in the pathogenesis of IgAN have been extensively described. Increased serum levels of IgA, mainly in the polymeric form, and the occurrence of circulating IgA immune complexes which localize in the glomeruli may be explained by an abnormal regulation of the IgA system. The disregulation of IgM-IgA switch may be implicated in this IgA disorder. Recent data have evidenced similar abnormalities in family members. PMID- 1924992 TI - [Hypothyroidism: current clinical, physiopathological and therapeutic aspects]. AB - The correct diagnosis and an appropriate classification of hypothyroidism must be considered on the light of the most recent physiopathological and molecular information. Hypothyroidism is no longer regarded as the rare disease characterized by a myxedematous condition as described since one century ago. With the present improvement of the diagnostic tools the thyroid hypofunction now includes all those blunted forms that are classified as subclinical or latent hypothyroidism. Thus, the hypothyroid syndrome, previously considered a rare event in its overt form, reaches a prevalence of 14% in female aged over fifty years. Following a coherent, concise historical review, the influence of age, surgery, drugs and autoimmunity on the etiology of the disease are critically discussed. The early detection and treatment of congenital hypothyroidism, to avoid an irreversible damage of the central nervous system, by means of the screening on the paper spot is also stressed. Replacement therapy with synthetic levothyroxine has to be personalized, according to the age and other clinical conditions, and should be prescribed also in the treatment of subclinical hypothyroidism. PMID- 1924993 TI - Nuclear accident countermeasures: iodine prophylaxis. Report of the UK Working Group on Iodine Prophylaxis following Nuclear Accidents. PMID- 1924994 TI - The fortification of yellow fats with vitamins A and D. Report of the Working Group on the Fortification of Yellow Fats. PMID- 1924995 TI - 38th Forum in Immunology. Histological organization of the spleen: implications for immune functions in different species. PMID- 1924996 TI - The human spleen and the immune system: not just another lymphoid organ. PMID- 1924997 TI - Histophysiology of autotransplanted splenic tissue. PMID- 1924998 TI - Non-lymphoid cells in the splenic white pulp. PMID- 1924999 TI - The humoral immune response in the spleen. PMID- 1925000 TI - B lymphocytes in the spleen: idiotype and anti-idiotype antibody-forming cells; qualitative and quantitative aspects of an in situ enzymehistochemical approach. PMID- 1925001 TI - T cells in the spleen: localization, cytokine production and cell/cell interactions. PMID- 1925002 TI - The unique role of the spleen and its compartments in lymphocyte migration. PMID- 1925003 TI - Outer PALS as an immunoproliferative microenvironment. PMID- 1925004 TI - Marginal zone B cells respond both to polysaccharide antigens and protein antigens. PMID- 1925005 TI - Histological organization of the spleen: implications for immune functions in amphibians. PMID- 1925006 TI - Morphological and immunological changes in the spleen of Xenopus laevis during metamorphosis. PMID- 1925007 TI - Structural and functional aspects of the spleen in bony fish. PMID- 1925008 TI - The complex of oriC DNA with the DnaA initiator protein. AB - We describe several experimental approaches relating to the early steps in the initiation of DNA replication at oriC. 1) A matrix is given which enables calculatation of the relative affinity of DnaA boxes for DnaA protein; 2) base changes within single Dna A boxes in oriC have little effect on oriC function; 3) mutations which change the distance between DnaA boxes inactivate oriC, but changes by one helical turn (+ and -) result in near wild-type oriC activity; 4) a Fis binding site was located at oriC coordinates 206-220; 5) KMnO4 probing demonstrates Dna-A-dependent unwinding in the left part of oriC in vivo and in vitro. PMID- 1925009 TI - E. coli minichromosome replication: regulation of initiation at oriC. AB - The initiation of Escherichia coli DNA replication is a highly regulated event with many parameters exerting positive and negative effects. The activity of the dnaA protein (the initiator protein) is profoundly influenced by the tight binding of the adenine nucleotides ATP and ADP. Further regulation of dnaA protein activity may occur through dnaA protein-cell membrane associations. A replicatively inactive form of dnaA protein is found aggregated with phospholipids; enzymatic treatment of the aggregates with phospholipase A2 or dnaK protein liberates dnaA protein with restored replication activity. Proper DNA structure is essential for replication. The energy stored in the DNA's supercoiling is crucial for dnaA protein's ability to initiate replication. Under conditions where strand-opening by dnaA protein is inhibited, such as low free superhelicity, an R-loop formed by RNA polymerase activates the origin at a distance by aiding strand-opening. A novel protein has been identified as a specific inhibitor of the initiation of DNA replication. This 33-kDa protein binds to the AT rich region of oriC and inhibits strand-opening by dnaA protein. PMID- 1925010 TI - Bacterial growth control studied by flow cytometry. AB - By employing flow cytometry, the DNA content and cell size of individual bacterial cells may be determined rapidly and with high precision. Also, the number of DNA replication origins in Escherichia coli cells can be measured after treating the cells with rifampicin together with the cell division inhibitor cephalexin. As opposed to wild type cells, certain mutants contain, with high frequency, a number of origins different from 2n, indicating that the mutants do not initiate DNA replication at all origins simultaneously. Here we give evidence that this asynchrony phenotype cannot occur as a consequence of aberrant chromosomal segregation or cell division, but can only be caused by defective coordination of multiple initiation events within one and the same cell. Flow cytometry has been used to perform exact and detailed analyses of the growth and cell cycle of E. coli. While the DNA distribution of a bacterial culture was unchanged as long as steady-state growth was maintained, the cellular DNA content was reduced when the culture approached and entered stationary phase. Only after prolonged incubation in stationary phase did the cells contain fully replicated chromosomes, and rapidly growing cells ended up with either 2 or 4 chromosomes in stationary phase. PMID- 1925011 TI - A calcium-binding protein that may be required for the initiation of chromosome replication in Escherichia coli. AB - Starvation for isoleucine but not for other amino acids in an ilv- strain or the addition of valine in an ilv+ strain inhibits initiation of chromosome and minichromosome replication in stringent (Rel+) Escherichia coli, but it does not inhibit replication in relaxed (relA) mutants (Guzman et al, 1988). From these results, we concluded that, (1) oriC initiation of replication is inhibited by ppGpp, and (2) isoleucine is not needed for the protein synthesis required at initiation. These results led us to find an isoleucine-free protein whose de novo synthesis is the sole protein synthesis requirement for oriC initiation. We also present evidence that this protein may be a calcium-binding protein located at 73 min in the genetic map. PMID- 1925012 TI - Analysis of a copy number mutant of plasmid pSC101: co-maintenance of wild type and mutant plasmids. AB - We have isolated a high copy number mutant of plasmid pSC101 which is maintained at a level 4 times higher than that of the wild type. The mutation is a single base change that maps in codon 93 of the initiation protein RepA. We find that the mutation relaxes the autoregulation of the protein but increases its affinity for the repeated sequences in the origin. The wild type and the mutant repA genes are co-dominant and the mutated protein acts in trans even in the presence of the wild type protein. Co-maintenance of the two types of plasmids results in an intermediate copy number. Computer simulation indicates that simple models can explain the behaviour of the two plasmids. PMID- 1925013 TI - Membrane attachment and DNA bending at the origin of the Escherichia coli chromosome. PMID- 1925014 TI - Only oriC and its flanking region are recovered from the complex formed at the time of initiation of chromosome replication in Escherichia coli. AB - The oriC region of Escherichia coli constructs a specific complex to associate with the outer membrane fraction (oriC complex). The oriC complex was periodically formed before as well as in the short period after initiation of DNA replication. Using the DNA extracted from outer membrane fractions of the cells just after initiation as a probe, the whole E. coli genomic library was assayed by plaque hybridization. DNA regions that hybridized with the probe corresponded to about a 100-kb length of chromosome DNA which included oriC. In addition, clones located in a counterclockwise direction from oriC were more preferentially hybridized among these positive clones. Thus, we conclude that the oriC region is a unique locus of the chromosome that binds to the outer membrane at the time of initiation of chromosome replication. PMID- 1925015 TI - The initiator titration model: computer simulation of chromosome and minichromosome control. AB - The initiator titration model was formulated to explain the initiation control of the bacterial chromosome. In particular, features concerning the replication behaviour of minichromosomes, such as their high copy number and Escherichia coli's ability to coinitiate chromosome and many minichromosome origins, were considered during the formulation of the model. The model is based on the initiator protein DnaA and its binding sites, DnaA boxes, in oriC, in the dnaA promoter and at other positions on the chromosome. Another important factor in the model is the eclipse period created by the hemimethylation of a new oriC which makes it refractory to initiation. The model was analysed by computer simulations using a stochastic approach varying the different input parameters, and the resulting computer cells were compared with data on living E. coli cells. Here we present the outcome of a few of these simulations concerning the eclipse period, in silico-shift experiments blocking initiation or elongation of replication, and introduction of minichromosomes into the computer cells. We also discuss the synthesis of DnaA protein in the computer cells. From our simulations, we conclude that, whether true or not, the model can mimic the in vivo initiation control of E. coli. PMID- 1925016 TI - The tus gene of Escherichia coli: autoregulation, analysis of flanking sequences and identification of a complementary system in Salmonella typhimurium. AB - The tus gene of Escherichia coli encodes a DNA-binding protein that, when bound to terminator sites, blocks replication forks. One of these sites, TerB, is immediately upstream from tus, and we have determined that the 5' end of tus mRNA is in the TerB site, that tus is autoregulated and that pTus is a very low efficiency promoter. Analysis of the DNA upstream from tus and TerB indicates a set of sensor/regulator genes which are comparable to envZ/ompR. Although tus mutants exhibit no growth phenotype in laboratory conditions, Salmonella typhimurium and E. coli have nevertheless maintained similar termination systems. Sequence homology can be demonstrated by Southern hybridizations, and the systems also exhibit functional complementation: the Tus protein of S. typhimurium blocks DNA replication at the TerA site of E. coli. PMID- 1925018 TI - Mutants defective in chromosome partitioning in E. coli. AB - Recent experimental results suggest that replicated daughter chromosomes (nucleoids) in Escherichia coli move non-progressively and abruptly at an early stage of the D (division) period from midcell toward the cell quarter positions, which will become the centres of the daughter cells. The chromosome positioning at the quarter positions was found to be controlled by the muk gene products. In muk mutants, normal size anucleate cells are spontaneously produced during cell division. The mukA gene is identical to the tolC gene encoding an outer membrane protein. The mukB gene codes for a 177-kDa protein. The amino acid sequence of the MukB protein deduced for the nucleotide sequence suggests that the MukB protein has five characteristic secondary structure domains: an amino-terminal globular domain containing a consensus sequence binding with ATP or another nucleotide. The central region of the protein consists of two alpha-helical coiled-coil domains and one globular domain. A carboxyl-terminal globular domain is rich in cysteine and positively charged residues arginine and lysine. Two MukB protein molecules might form a homodimer in the coiled-coil regions. The predicted secondary structure of the MukB protein suggests that the protein provides the force required for the positioning of nucleoids from midcell toward the cell quarters. The mukC and mukD genes are located at 88 and 41 min of the chromosome map, respectively. PMID- 1925017 TI - In vivo effect of the tus mutation on cell division in an Escherichia coli strain where chromosome replication is under the control of plasmid R1. AB - The phenotypic effect of the tus::kan mutation in an Escherichia coli strain, where the chromosome is replicated unidirectionally by an integrated R1 miniplasmid, was examined by flow cytometry and phase fluorescence microscopy. The tus+ cells exhibited perturbed cell division, as indicated by the presence of many elongated cells and filaments. Inactivation of the tus gene led to a reduction in the frequency of such elongated cells, presumably by eliminating Tus mediated polar arrests of replication forks at ter sites, thereby shortening the time required for completion of chromosome replication. PMID- 1925019 TI - Characterization of Escherichia coli mutants with altered ploidy. AB - We describe the isolation and characterization of new mutants in the cell cycle of Escherichia coli. The mutants were selected as gain of function mutants that are able to maintain more than the normal number of chromosomes. Our increased ploidy mutants were isolated as resistant to camphor vapours, which selects for cells with more chromosomes than normal. The mutants (called mbr for moth-ball resistant) map to four chromosomal locations: mbrA at 68 min; mbrB at 88.5 min; mbrC at 89.5 min; and mbrD at 90 min. To investigate the nature of these cell cycle mutants, we have coupled them with defects in recA, to test for induction of the SOS response, and dam, to determine if methylation is required for mbr function. Based on the results of these and other tests, we have made a preliminary placement of the mbr mutants within the context of the cell cycle. mbrA mutations appear to be defective in the coupling of the DNA replication cycle to the cell division cycle, and as such, may define a new link between the two processes. mbrB does not seem to be able to coordinate the cell cycle and the growth rate of the cell. mbrC appears to be defective in partitioning of chromosomes. mbrD, which may be allelic to rpoB (a subunit of RNA polymerase), appears to be defective in either chromosomal partitioning or the later stages of DNA replication. PMID- 1925020 TI - Analysis of a myosin-like protein and the role of calcium in the E. coli cell cycle. AB - For a number of years now, we have argued that current models for the control of initiation of DNA synthesis, chromosomal partitioning and septum formation in Escherichia coli are unsatisfactory. Indeed, we could argue that despite considerable efforts, with the possible exception of dnaA and ftsZ, no genes specifically implicated in these control processes have been identified. In the cases of DnaA and FtsZ, no evidence has appeared to indicate how such molecules might be regulated to act once per cycle. In 1988, we formulated a specific proposal that the timing of cell cycle events in E. coli might be determined by a Ca++ flux, mediated by calcium-binding proteins and protein kinases and culminating, in the case of chromosome segregation and division, in the action of force-generating proteins such as myosin (Norris et al., 1988). In formulating this proposal, we took the view that the fundamental elements of cell cycle regulation are likely to be highly conserved across all species including prokaryotes. In this presentation, we shall describe the approaches we have been taking in order to test this hypothesis and to summarize the data obtained, in particular in relation to new genes identified which may play a role in the E. coli cell cycle. We shall also briefly indicate recent data from other laboratories consistent with our general hypothesis. PMID- 1925021 TI - Unique sequence requirements for the P1 plasmid replication origin. AB - We have carried out a detailed genetic analysis of the P1 plasmid replication origin and shown that it has four major structural requirements: the DnaA box, a series of five 7-base pair (bp) repeats, a GC-rich spacer and five 19-bp repeats that bind the P1 RepA protein. The origin requires the DnaA protein and its recognition sequence (the DnaA box). However, although five boxes are present in two separate blocks in the wild type, just one, placed either to the left or right of the core origin sequences, is sufficient for function as long as the box conforms exactly to the proposed consensus. Each of the five 7-bp repeats that constitute the core of the origin is required; mutations within any of the first six base pairs can block origin function. The required bases include, but are not limited to, those constituting dam methylation sites. Also essential is a 39-bp GC-rich sequence. We show this to be a spacer of critical length that separates the 7-bp repeats from the last required region; a series of 19-bp repeats that bind the P1 RepA initiator protein. PMID- 1925022 TI - Functional consequences of improved structural information on bacterial nucleoids. AB - Section of Escherichia coli cells, cryofixed, freeze-substituted into acetone and resin-embedded, show nucleoids with coralline shape. The excrescencies reach far into the cytoplasm. Membrane contact is no longer excluded. Comparison with phase contrast light microscopy shows that the fine excrescencies cannot be resolved and therefore lead "artificially" to a more confined aspect of the nucleoid. The packing density of the DNA in the nucleoids is like that of eukaryotic interphase nuclei and would thus allow diffusion in and out of even large macromolecules. The transcription has, however, been demonstrated to occur only at the periphery; it requires a very dynamic state of the chromatin. The chromatin fine structure is now more granular than fibrillar, as it was previously. The granular structure is compatible with--but there is no proof for--the existence of compactosomes, which would form as a consequence of unrestrained supercoiling. PMID- 1925023 TI - HU and IHF: similarities and differences. In Escherichia coli, the lack of HU is not compensated for by IHF. AB - HU is one of the most abundant DNA binding proteins in Escherichia coli. Like the histones, HU is able to condense DNA in vitro and to introduce negative super coiling in covalently closed circular, relaxed DNA molecules in the presence of topoisomerase I. HU is well conserved in all prokaryotes but surprisingly, it is also homologous to another E. coli DNA-binding protein, IHF. Contrary to HU, IHF shows sequence specificity and is much less abundant that HU. Both are heterodimers and all four polypeptide chains probably arose from a common ancestor. The question we raised was whether IHF could supply the main functions of HU in its absence. The answer seems to be negative for the following reasons. We did not observe any significant regulation of expression of the genes coding for HU by IHF, or vice-versa. The structures that these two proteins form with double-stranded or single-stranded DNA are completely different. Finally, overexpression of IHF does not relieve the growth defects observed in HU-less mutants. However, it can be speculated from our results that even if the two proteins are not equivalent and cannot replace one another, both could stimulate (or inhibit) some specific protein-DNA interactions or affect the DNA-binding properties of one another. PMID- 1925024 TI - FtsZ and cell division. AB - The ftsZ gene in Escherichia coli is thought to be an essential gene and to play a pivotal role in cell division. Gene disruption experiments confirmed that ftsZ is an essential gene. Examination of cellular responses to FtsZ depletion indicated that FtsZ was required for division but not for nucleoid segregation. Analysis of mutations within the ftsZ, gene, selected for resistance to the cell division inhibitor SulA, revealed that they also conferred resistance to MinCD. This raises the possibility that ftsZ is the target of these two cell division inhibitors. Analysis of the ftsZ gene from Bacillus subtilis revealed that the gene was required for both septation during vegetative growth and asymmetric septation during sporulation. PMID- 1925025 TI - On the chronology and topography of bacterial cell division. AB - Gene products that play a role in the formation of cell septum should be expected to be endowed with a set of specific properties. In principle, septal proteins should be located at the cell envelope. The expression of division genes should ensure the synthesis of septal proteins at levels commensurate with the needs of cell division at different rates of cell duplication. We have results indicating that some fts genes located within the 2.5-min cluster in the Escherichia coli chromosome conform to these predictions. PMID- 1925026 TI - Structure and function of the ftsH gene in Escherichia coli. AB - The ftsH mutant Y16 shows thermosensitive filamentation with reduced amounts of penicillin-binding protein 3 (PBP3) (Ferreira et al., 1987). Genetic analysis, however, showed that the lethality of the ftsH mutation was not due to a lack of PBP3 activity alone. The ftsH gene was cloned and sequenced and the FtsH protein was deduced to be a membrane protein of 70.7 kDa which has an ATP-binding domain. Highly significant homology of amino acid sequence was observed between FtsH protein and two eukaryotic proteins, yeast Saccharomyces cerevisiae Sec 18p and its mammalian homologue NSF, which are involved in protein transport pathways. This suggests that FtsH protein may act for translocation of specific proteins including PBP3 and at least one other additional protein essential for cell growth. Suppressor mutants of Y16, which were able to grow at 42 degrees C, were isolated, and the suppressor mutations (sfh) were mapped to 16 min. A wild type chromosomal fragment able to complement the sfh mutations was cloned. We also identified another gene (ftsJ) affecting cell division in the region upstream of the ftsH gene. PMID- 1925027 TI - Three genes preceding pyrE on the Escherichia coli chromosome are essential for survival and normal cell morphology in stationary culture and at high temperature. AB - Previous studies of the upstream region of the pyrE gene in Escherichia coli revealed three genes of unknown function. Inactivation of these genes (designated orfE, orfX and orfY) by crossing the KmR-cassette-disrupted orf into the chromosome indicated that they were not required during exponential growth (Poulsen et al., Mol., Microbiol., 1989 b). Here we report that the three genes are of importance in the stationary phase. Thus, cultures of the mutants grown to a stationary state in rich media contained bacterial filaments of abnormal morphology. In addition, flow cytometric analyses showed that outgrown cultures of the orf mutants have anomalous size distribution and DNA content, and that rifampicin treatment of exponentially growing mutants results in cell populations with chromosome numbers in the range from about 1 to 10, compared with wild type strains that end up with 4 and 8 full chromosomes. Finally, it appeared that the three orf's are indispensable at high temperatures since the insertion mutants were unable to form colonies above 45 degrees C and since cultures of exponentially growing mutants lysed upon a temperature shift from 37 degrees C to 45 degrees C. PMID- 1925029 TI - Toporegulation of bacterial division according to the nucleoid occlusion model. AB - A model for the toporegulation of division in Escherichia coli is presented in which cell constriction is initiated by the combined action of a biochemical and a structural event. It is proposed that the biochemical event of termination of DNA replication causes a transient change in the pool of deoxyribonucleotides, which serves as a localized trigger that is converted to a diffusible, cytoplasmic activator of peptidoglycan synthesis. The second event involves the segregation of the nucleoids. Evidence is presented that the nucleoid suppresses the activity of peptidoglycan synthesis in its vicinity. It is proposed that active transcription/translation around the nucleoids produces a strong but short range inhibitor which prohibits division (nucleoid occlusion). The combined effects of the locally produced termination-activator and of the diminished occlusion as a result of nucleoid segregation, guarantee that division is normally placed between the separated nucleoids. The model can explain the pattern of division-recovery of filaments, the majority of which constrict at sites which produce polar daughter cells containing two nucleoids. In addition, the model offers an explanation for the occurrence of mini-cells under a variety of conditions. PMID- 1925028 TI - Localization of the membrane binding sites of Era in Escherichia coli. AB - Era is a GTP-binding protein that is essential for normal cell growth and division in Escherichia coli. In view of the fact that eukaryotic proteins similar to Era are membrane-associated and important in membrane signalling pathways, experiments were carried out to establish the intracellular location of Era. Immunoelectron microscopy was employed to demonstrate that Era resides at or very near the internal surface of the cytoplasmic membrane, which is a location expected for a membrane signalling protein. In addition, Era occurs in patches that may correspond to areas that are potential sites of septation. PMID- 1925030 TI - Biogenesis of cell division sites in ftsA and ftsZ filaments. AB - The development of nascent cell division sites was studied in Escherichia coli strains containing ftsAts and ftsZts mutations in which septal development is arrested after shift to the restrictive temperature. Division sites were studied by measuring positions of plasmolysis bays, a visible marker for periseptal annuli. Annuli are circumferential zones of membrane adhesion which represent the earliest known structural differentiation at developing septal sites. Two patterns of annulus development were observed in the mutant strains. Normal numbers of new annuli were generated in filaments of both mutants, but in ftsZ filaments annuli failed to mature and to become properly localized, suggesting that ftsZ gene product is first required for maturation of annuli. In contrast, mature annuli accumulated at division sites in ftsA filaments, suggesting that the ftsA gene product is required at a stage after maturation and localization of nascent annuli. PMID- 1925031 TI - Murein chemistry of cell division in Escherichia coli. AB - The length distribution of the glycan strands of murein has been analysed with a novel method in filamentous and spherical cells of Escherichia coli, as well as during septum formation and cell separation. A shift to the longer glycan strands was observed in the murein of furazlocillin-induced filaments. In contrast, shorter glycan strands were increased in the murein of mecillinam-induced spherical cells. During septum formation in a chain-forming envA mutant that is defective in the splitting process of the septum, a shift to the shorter glycan strands was detected that was not seen in wild type E. coli cells. It is concluded that septum-specific murein structures of rather short glycan strands are released during splitting of the septum. This intermediate material remains present in the septum of the envA mutant. The splitting process of the septum was investigated by analysing the murein during penicillin-induced bacteriolysis, which is known to take place by strictly localized murein degradation in the equatorial zone of the cell. No changes in the length distribution of the glycan strands could be detected during penicillin-induced lysis, with the exception of an increase in disaccharides, the shortest glycan strands possible. This is explained by the action of exo-muramidases progressively digesting glycan strands, leaving disaccharide units covalently linked to the remaining murein at the sites of murein cross-linkage. It is proposed that this "zipper-like" mechanism represents the normal cutting process of the septum during cell separation. PMID- 1925032 TI - On the role of the high molecular weight penicillin-binding proteins in the cell cycle of Escherichia coli. AB - Blocking of penicillin-binding proteins (PBP) 2 or 3 of Escherichia coli by specific antibiotics led to inhibition of peptidoglycan synthesis measured as rate of 3H-Dap incorporation. The inhibition was ca 60% by mecillinam (blocking PBP2) and ca 35% by cephalexin or furazlocillin (both specific for PBP3). PBP3 could be inhibited primarily during constriction, whereas the inhibition of PBP2 was observed throughout the cell cycle. The ratio of PBP2 and 3 activities appeared to be correlated with cell shape, i.e. in long rods, inhibition of peptidoglycan synthesis by mecillinam was stronger than in short rods. Inhibition studies with the PBP1A/1B-specific antibiotic cefsulodin showed that, with a delay of approximately 1/2 mass-doubling time, peptidoglycan synthesis was inhibited completely with concomitant lysis. The cefsulodin-induced lysis was independent of the stage of the cell cycle. It was suggested that PBP1A/1B do not have a specific function in either elongation or constriction. Rather, they seem to have a general activity on the basis of which the other synthesizing PBP perform their special tasks. This interpretation is formulated as a "primer model of peptidoglycan synthesis". PMID- 1925033 TI - Effect of D-amino acids on Escherichia coli strains with impaired penicillin binding proteins. AB - Escherichia coli cells growing in the presence of some D-amino acids incorporate D-amino acid into the peptidoglycan layer of the cell wall by a mechanism most likely independent of the normal biosynthetic pathway. Analysis of the sensitivity of mutant strains with impaired penicillin-binding proteins (PBP) to D-amino acids indicated that ponB and DD-endopeptidase/DD-carboxypeptidase-I defective strains are hypersensitive to D-amino acids. D-tryptophan containing peptidoglycan was found to be more susceptible to the action of lytic transglycosilases than native material, which could explain in part the harmful effects of D-amino acids. ponB strains carrying additional mutations suppressing hypersensitivity to D-amino acids have been obtained and the results of their initial characterization are reported. PMID- 1925034 TI - Physical education's role in public health. AB - The public health community is becoming increasingly interested in the potential contributions of school physical education to child health. School physical education is seen as an ideal site for the promotion of regular physical activity because up to 97% of elementary school children participate in some sort of physical education program. For maximal public health benefit, school physical education programs should prepare children for a lifetime of physical activity. This public health goal for physical education may require some changes in current approaches. Physical educators are challenged to collaborate with public health professionals in developing and evaluating school physical education programs that will improve the health of the nation's youth. PMID- 1925035 TI - Physical education's role in achieving national health objectives. PMID- 1925036 TI - The role of school physical education in public health. PMID- 1925037 TI - The role of physical education and children's activity in the public health. PMID- 1925038 TI - The role of physical education in the development of active lifestyles. AB - If elementary physical education existed just to achieve "present" goals, especially regular exercise, the nature of the program would be clearer and the need for trained teachers less. It is the "future" goal that complicates the debate over the elementary program. It is the "future" goal that requires a broader range of experiences and a developmental approach. Because we are preparing students to implement an active lifestyle in adulthood, the development of sport and dance skills through age/ability-appropriate and sequential lessons is an important as the "present" opportunity for physical activity. Teachers must be knowledgeable in the subdisciplines of physical education and well versed in those teaching methods that promote vigorous activity and maximum participation. The lifetime public health goal dictates we help students develop a knowledge base about exercise and health. This goal requires us to learn more than we presently know about promoting positive attitudes toward and fostering appreciations for healthful living. The hope for improved adult health also requires a K-12 curricular model in which every year continues previous experiences and moves students closer to the goal as those students are changing physically, mentally, and socially. The next debate should focus on the role of secondary school physical education in linking health-related elementary programs to healthy adult lifestyles. Even though we do not fully understand the relationship between school physical education and active adult lifestyles, our best bet is developing a continuous, developmental K-12 curriculum. PMID- 1925039 TI - Physical activity, cardiovascular fitness, and adiposity in children. AB - With cardiovascular fitness (CVF) as the dependent variable, relationships with habitual level of physical activity, age, gender, and body mass index (BMI) were investigated in a sample of 93 high adiposity and 93 low adiposity children, ages 8 to 13. A physical activity score (PAS) was computed for each child from a 2-day observation period. A physical working capacity index from cycle ergometry (PWC170) was the measure of CVF. Low and high adiposity samples were classified by a median split (42.9 mm) on the sum of three skinfold measures (tricep, suprailiac, subscapula). For the high adiposity sample, PAS, age, BMI, and gender were significant and the overall model was significant (p less than .001), accounting for 38% of variance in PWC170. In the low adiposity sample, gender (p less than .04) was significantly related to CVF, but the overall model was not significant (p less than .35). PAS, thus, was a significant predictor of CVF among the high adiposity children, but not the low adiposity children. Mechanisms that may account for this difference include greater work for equal activity among the obese, a ceiling effect on CVF among the low adiposity children, or differences in hormonal or metabolic factors mediating the activity-CVF relationship. PMID- 1925040 TI - Prized performers, but frequently overlooked students: the involvement of black athletes in intercollegiate sports on predominantly white university campuses, 1890-1972. PMID- 1925041 TI - Age-related differences in response programming. AB - Age-related differential effects on reaction time (RT) performance for movement complexity and response-response (R-R) compatibility were examined in children, adolescents, and young adults. A two-choice RT paradigm involved three different finger responses, and each finger movement response was paired with every other movement response. Movement complexity was manipulated by varying the digits activated and was measured as the mean RT for a particular movement across all choice pairs. R-R compatibility was manipulated by altering the pairing of choice alternatives and was determined by the mean RT comparison for each of the movements according to the paired choice alternative. Simple RTs were also obtained for all finger movement responses for comparison with the RTs achieved in choice situations. Age-related differences were found for both movement complexity and R-R compatibility. Mean RT and response consistency improved with age. Although higher overall speeds were found with age, adolescents were not significantly slower than young adults. Adolescents did, however, make significantly fewer response errors on movements differing in complexity. Bilateral versus unilateral control and number of fingers involved in the task were found to affect both movement complexity and the compatibility between response pairs. The relationship between the alternative and choice response was found to be a robust factor affecting R-R compatibility. Choice responses were significantly slower than simple responses, and the rank ordering of movement responses was identical within the two paradigms. PMID- 1925042 TI - Composition of practice: influence on the retention of motor skills. AB - The purpose of these experiments was to investigate further the variable practice effect found by Shea and Kohl (1990). Experiment 1 was an initial attempt to determine the locus of the retention benefits demonstrated by subjects provided variable practice experiences. All groups received 20 acquisition blocks consisting of five test trials per block at a target of 150 N. The interval between test trials was either unfilled or filled, with additional trials consisting of the same target force, variable target forces, or practice on an unrelated motor task. The results indicated retention was not incremented (relative to an unfilled interval) by requiring subjects to perform an unrelated motor task in the intertest-trial interval. However, when the interest-trial interval was filled with practice on related motor tasks, retention was significantly improved. Experiment 2 assessed the impact of increasing the number of related motor tasks interpolated between test trials. The results indicated filling the intertest-trial interval with one motor task resulted in large retention benefits relative to an unfilled interval. Further increases in the number of related motor tasks (3) interpolated between test trials resulted in only modest increments to retention. The results were consistent with the elaboration perspective proposed by Shea and Zimny (1983). The elaboration perspective proposes that the simultaneous presence of related items in working memory facilitates interitem elaborative and distinctive processing that ultimately results in retention benefits. PMID- 1925044 TI - A participant-observation study of knowledge restructuring in a field-based elementary physical education methods course. AB - This paper describes how seven undergraduate students restructured knowledge during a field-based elementary physical education methods course. Guided by the teacher educator the students planned, taught, and reflected on a series of lessons to children in an elementary school. Theoretical course knowledge was integrated into planning and reflecting sessions. Data were collected and analyzed using interpretive research methodologies. The researcher observed and recorded field notes during all class sessions, conducted three formal and many informal interviews with all seven students, and collected available, pertinent documents. All data were categorized, and similarities in what and how the students learned were identified. The students reported knowledge restructuring as a salient aspect of field-based learning. Based on a cognitive theoretical perspective, this study described students as active, goal-oriented learners who, at times, recognized and restructured problematic prior knowledge to form a more differentiated understanding of teaching and children. PMID- 1925043 TI - Differences between experienced and inexperienced teachers' planning decisions, interactions, student engagement, and instructional climate. AB - This study focused on the differences between experienced and inexperienced physical education teachers' approaches to planning, low inference indicators of teaching behavior during instruction, and global variables from the Beginning Teacher Evaluation Study. It was found experienced teachers asked many more questions before they began planning than did inexperienced teachers. Experienced teachers' plans reflected a concern about contingencies that might arise during instruction, whereas inexperienced teachers' plans did not. Interaction analysis and codings of student engagement showed marked differences between experienced and inexperienced teachers. Judging the qualities of experienced and inexperienced teachers also showed important differences. These sources of data are interrelated and give a vivid picture of how experienced and inexperienced teachers differ in accomplishment of instruction. The findings are discussed in terms of what they may mean for teacher development programs. PMID- 1925045 TI - Postexercise energy expenditure following upper body exercise. AB - This study was designed to examine the magnitude and duration of excess postexercise oxygen consumption (EPOC) following upper body exercise, using lower body exercise for comparison. On separate days and in a counterbalanced order, eight subjects (four male and four female) performed a 20-min exercise at 60% of mode-specific peak oxygen uptake (VO2) using an arm crank and cycle ergometer. Prior to each exercise, baseline VO2 and heart rate (HR) were measured during the final 15 min of a 45-min seated rest. VO2 and HR were measured continuously during the postexercise period until baseline VO2 was reestablished. No significant difference between the two experimental conditions was found for magnitude of EPOC (t [7] = 0.69, p greater than .05). Mean (+/- SD) values were 9.2 +/- 3.3 and 10.4 +/- 5.8 kcal for the arm crank and cycle ergometer exercises, respectively. Duration of EPOC was relatively short and not significantly different (t [7] = 0.24, p greater than .05) between the upper body (22.9 +/- 13.7 min) and lower body (24.2 +/- 19.4 min) exercises. Within the framework of the chosen exercise conditions, these results suggest EPOC may be related primarily to the relative metabolic rate of the active musculature, as opposed to the absolute exercise VO2 or quantity of active muscle mass associated with these two types of exercise. PMID- 1925046 TI - Teacher versus peer models revisited: effects on motor performance and self efficacy. AB - This study reinvestigated and extended the findings of Landers and Landers (1973), which examined the influence of skilled and unskilled teacher and peer models on motor performance. Sixth grade females (N = 100) were randomly assigned to groups in a 2 x 2 (Model Type x Model Skill) factorial design or to a no-model group. In the treatment groups, subjects observed one of four unfamiliar models- (a) a skilled teacher, (b) an unskilled teacher, (c) a skilled peer, or (d) an unskilled peer--perform on the Bachman ladder task. Subjects performed 30 trials of the task and also completed self-efficacy questionnaires on three occasions. Results showed that subjects who watched a skilled model performed better than subjects who watched an unskilled model. Unlike the Landers and Landers study, no model type by model skill interaction was found. In addition, the skilled model group reported higher efficacy beliefs than the control group after performing and were more efficacious than the unskilled model subjects both after watching the model and after performing. These results suggest when students view unfamiliar models, the skill rather than the status of the model may be more salient. PMID- 1925047 TI - Youth fitness testing: the effect of percentile-based evaluative feedback on intrinsic motivation. AB - This study was a test of Deci and Ryan's (1985) cognitive evaluation theory in a fitness testing situation. More specifically, it was a test of Proposition 2 of that theory, which posits that external events that increase or decrease perceived competence will increase or decrease intrinsic motivation. Seventh and eighth grade schoolchildren (N = 105) volunteered for an experiment that was ostensibly to collect data on a new youth fitness test (the Illinois Agility Run). After two untimed practice runs, a specially adapted version of the Intrinsic Motivation Inventory (IMI) was administered as a pretest of intrinsic motivation. Two weeks later when subjects ran again, they were apparently electronically timed. In reality, the subjects were given bogus feedback. Subjects in a positive feedback condition were told their scores were above the 80th percentile, while those in a negative feedback condition were told their scores were below the 20th percentile. Those in a control condition received no feedback. The IMI was again administered to the subjects after their runs. Multivariate and subsequent univariate tests were significant for all four subscale dependent variables (perceived interest-enjoyment, competence, effort, and pressure-tension). Positive feedback enhanced all aspects of intrinsic motivation, whereas negative feedback decreased them. In a further test of cognitive evaluation theory, path analysis results supported the prediction that perceived competence would mediate changes in the other IMI subscales. Taken together, these results clearly support cognitive evaluation theory and also may have important implications regarding motivation for those who administer youth fitness tests. PMID- 1925048 TI - The time structure of the block in volleyball: a comparison of different step techniques. PMID- 1925049 TI - Maximal responses to treadmill and deep water running in high school female cross country runners. PMID- 1925050 TI - The use of contextual interference trials by mildly mentally handicapped children. PMID- 1925051 TI - Accuracy of references in research quarterly for exercise and sport. PMID- 1925052 TI - Prelongitudinal screening of hypothesized developmental sequences for the overhead tennis serve in experienced tennis players 9-19 years of age. AB - A cross-sectional study was conducted to investigate developmental characteristics within six body component actions for the overhead serve in tennis and to determine if such actions should be validated through longitudinal study. Developmental sequences, hypothesized for two components during the preparatory phase and four components during the force production phase of the overhead tennis serve, were used to classify the videotaped serving actions of 30 male and 30 female tennis players. Sequences hypothesized for the Preparatory Trunk, Elbow, and Forearm/Racket actions met the prelongitudinal screening criteria proposed by Roberton (1978); Roberton, Williams, and Langendorfer (1980); and Langendorfer (1982). Sequences for these component actions should be validated through longitudinal study. Steps within sequences for the Preparatory Backswing, Trunk for Force, and Feet/Legs are apparently misordered or not characteristic of a developmental process. Further cross-sectional study of these component actions prior to longitudinal study is recommended. PMID- 1925053 TI - Developmental sequences for catching a small ball: a prelongitudinal screening. AB - Developmental sequences are identified for many skills (e.g., hopping and throwing). Sequences are hypothesized but not validated for catching. Two purposes of this investigation were to validate hypothesized catching sequences and examine the importance of task constraints on catching performance. Seventy two subjects (5-12 years of age) were videotaped as they attempted to catch a small (10-cm) ball, tossed to three locations: (a) directly to the body, (b) at the forehead, and (c) to various other locations. Trials were categorized using developmental sequences including four components: arm preparation, arm reception, hands, and body. The data were analyzed by catching condition using the prelongitudinal screening procedure described by Roberton, Williams, and Langendorfer (1980). Preliminary screening resulted in clarification of descriptions for several developmental levels. Movement sequences for hand and body components were comprehensive and age-related for the groups studied. Task conditions differently constrained children of different ages. Arm components did not meet the Roberton et al. criteria. Combining them may be warranted. Varying ball size or type is needed to test the comprehensiveness of the proposed sequences for other catching skills. PMID- 1925054 TI - Stimulus intensity and experimental design effects on motor response processing. AB - Experimental design effects and range effects may have influenced previous studies on motor response processing (Grice & Hunter, 1964; Grice, Nullmeyer, & Schnizlein, 1979; Poulton, 1973). This investigation was conducted concurrently with two experiments. First, Erlebacher's (1977) more powerful analysis of variance (ANOVA) model, which allows for the testing of the independent variable (stimulus intensity effect), the experimental design effect (between-subjects [BS] vs. within-subjects [WS]), and the important interaction between independent variable and experimental design was utilized to clarify if the nature of the experimental design (BS, WS) biases motor response processing. Second, Erlebacher's (1977) ANOVA model was used to determine if motor response processing was affected by stimulus intensity and experimental design when different ranges of auditory stimuli were compared. Results indicate motor response processing was inversely affected by increasing stimulus intensity. Experimental design effects and range effects did not appear to bias motor response processing. We conclude stimulus intensity effects on motor response processing appear to be the result of true neuromotor functioning and not artifacts of experimental design or of range effects. PMID- 1925056 TI - Summary knowledge of results. AB - Summary knowledge of results (KR) involves delaying the presentation of KR until a predetermined number of trials has been completed. Schmidt, Young, Swinnen, and Shapiro (1989) found an optimal summary length of 15 trials (compared to 1, 5, and 10) and Schmidt, Lange, and Young (1990) found an optimum length of 5 trials (compared to 1, 10, and 15) for 1 and 2 kinematic degree of freedom timing tasks, respectively. Experiment 1 was designed to determine the optimal summary length for learning a simple isometric force production task. The results indicated better retention for the 16-trial summary than for 8- or 1-trial summaries. Experiment 2 was an initial attempt to determine the locus of the 16-trial summary effect. Specifically, Experiment 2 focused on the role played by both the information provided in the summary presentations and the practice per se of the first 14 trials in the 16-trial block. The results suggest KR is important to ensure response stability. However, it also appears important to restrict the subject's immediate utilization of KR. This latter requirement may potentially aid the parameterization process, resulting in a reduction in response bias. PMID- 1925055 TI - Acquiring an attacking forehand drive: the effects of static and dynamic environmental conditions. AB - Two groups of 10 novice subjects each were trained to perform attacking forehand drives in table tennis and land the balls as fast and as accurately as possible onto a target on the opposite side of the net under two different training conditions. Under the static training condition, the balls were to be struck from a constant position, and under the dynamic training condition, balls approached the subjects in a normal way. Both groups were tested under dynamic conditions prior to and after four days of training, during which they received 1,600 practice trials. Both groups of subjects were shown to increase the number of balls that landed on the target, and learning was also evident from an increased consistency of the direction of travel of the bat at the moment of ball/bat contact. However, no increase in consistency was found for the location of the bat at the moment of ball/bat contact and for the movement times. Thus, learning can occur in the absence of externally generated time-to-contact information, but this is not due to the establishment of a consistent movement form. Learning appears to progress from control at the moment of ball/bat contact backward, toward the moment of initiation. PMID- 1925057 TI - When forgetting benefits motor retention. AB - Recent research (Lee & Weeks, 1987; Weeks, Lee, & Elliott, 1987) investigating the processes responsible for the contextual interference phenomenon has used a modified short-term motor retention paradigm to support the reconstruction explanation (Lee & Magill, 1985; Magill, 1989; Magill & Hall, 1990). The present experiment was an extension of these experiments in which forgetting of an acquisition task was induced through performance of either a similar or dissimilar distractor task during the intertrial interval. The effects of an extra practice trial with the acquisition task as well as no activity during the intertrial interval were also investigated. In addition, forgetting of the acquisition task was assessed prior to a reconstruction trial, which immediately preceded a 2-min filled retention interval. Both similar and dissimilar distractor tasks caused equivalent amounts of forgetting of the acquisition task prior to the reconstruction trial. However, retention of the acquisition task was significantly improved if its reconstruction occurred following forgetting due to interference from performance of a similar distractor task. These findings suggest forgetting and subsequent reconstruction alone are not sufficient for improved retention. These processes must occur in the context of a similar task for improved retention. PMID- 1925059 TI - Description of knowledge structures within a concept-based curriculum framework. AB - The development of declarative knowledge was examined within the parameters of movement-based curricula. Declarative knowledge represents factual or foundational knowledge frequently articulated as curriculum content. A semantic ordered tree technique was used to investigate the knowledge structures of three groups of teacher preparation subjects (novice, coursework, student teacher) and one group of elementary physical education teachers (experts). Structures were examined based on frequency and coherence criteria. ANOVA was used to examine differences between groups. Results suggested that declarative knowledge appeared to develop in complexity from novice to expert within the parameters of concept based movement curricula. The Active Structural Networks Theory was used to interpret structural development through the accretion, tuning, and restructuring phases. Knowledge structures of the novice and coursework groups seemed to represent accretion, whereas those of student teachers and experts represented tuning and restructuring. PMID- 1925058 TI - Distance and location assimilation effects in rapid bimanual movement. AB - When subjects make simultaneous aiming movements of the upper limbs over different distances, assimilation effects are shown; the shorter distance limb overshoots when paired with a longer distance limb. However, it is not known whether assimilation effects are due to variations in distance per se or to variations in target location. To separate the possible influences of distance and location, 60 subjects made rapid bimanual aiming movements in one of four conditions. The two different-distance groups made a 20 degrees movement in the left hand and a 60 degrees movement in the right hand to either the same or different target locations. The comparison groups moved 20 degrees in each limb. Somewhat surprisingly, spatial assimilations were greater when moving different distances to the same, rather than different, target locations, which suggests interlimb differences in distance mediate assimilation effects rather than target location. Temporal assimilations were greater when distance and location were varied, but the assimilations were not related to interlimb differences in velocity, as predicted by Marteniuk and MacKenzie (1980). PMID- 1925060 TI - The validity of academic learning time-physical education (ALT-PE) as a process measure of achievement. AB - The purpose of this study was to determine whether the ALT-PE system (Version 2) is valid as a process approach to estimate student achievement. Students (N = 60) were randomly selected from a data base that includes pretest and posttest scores for two volleyball skills and seven sessions of videotaped instruction. Videotapes were collected using two cameras with a split-screen generator so most instruction and practice could be seen. ALT-PE data were coded from the videotapes. In addition to normal ALT-PE coding conventions, coders recorded the skill that was the focus of instruction. Combinations of context and learner involvement categories were summed for each skill across the seven class sessions and to form other logical categories (e.g., total motor appropriate intervals). Achievement scores were calculated by posttest on pretest regression for each skill with the residual score used for subsequent analysis. Residual achievement scores were correlated with summed ALT-PE categories. The results indicate for the serve both total motor appropriate and practice-motor appropriate intervals were related to student achievement. For the pass, practice-motor appropriate intervals were related to achievement and the total motor appropriate-achievement correlation failed significance. These results demonstrate the validity of the ALT-PE system as a process measure of achievement can be partially substantiated. PMID- 1925061 TI - Cardiac structure and function in weight trainers, runners, and runner/weight trainers. AB - The purpose of this study was to describe and compare cardiac structure and function in adult male weight trainers, runners, and those who do both activities. Subjects had actively participated in the various training programs for the previous five years. Age ranged from 28.4 to 31.3 years in the three groups. Echocardiography was used to assess selected heart diameters, volumes, indices of contractility, and thicknesses, while VO2 max and percent body fat were measured using standard methods. Heart structure and function were expressed in absolute terms and relative to total body weight. An alpha level of .05 was used in all comparisons. Results indicated the runners demonstrated significantly greater relative LVIDd, LVIDs, and LVPW than the weight trainers. The runner/weight trainers possessed significantly greater relative LVIDd, LVIDs, LVPW, IVS, and LVEDV than the weight trainers. No significant differences, absolute or relative, existed between the runner and runner/weight trainer groups in any of the myocardial structure and function variables. It was concluded that men who run or run and weight train have similar structural and functional characteristics of the heart and possess greater relative internal diameter and left ventricular wall thickness than men who only weight train. PMID- 1925062 TI - The relationship between age and optimal performance of elite athletes in endurance running events. PMID- 1925063 TI - Qualitative assessment of the backswing in older adult throwing. PMID- 1925064 TI - What is missing in p less than .05? Effect size. PMID- 1925065 TI - Response to "A comparison of reliability estimation using trials-to-criterion and sequential probability ratio testing". PMID- 1925066 TI - Influence of glycogen content, temperature, and Euro Collins solution on membrane potential and sodium activity of superfused porcine liver slices. AB - The influence of glycogen content, temperature, and Euro Collins (EC) solution on membrane potential (Vm) and intracellular sodium activity (aNai) were measured in cells of superfused porcine liver slices by means of double-barrelled ion sensitive microelectrodes. Vm was -26.1mV in fasted pigs and -20.6mV after glucose feeding, when measured in HEPES-buffered solution (P less than 0.0001). aNai was not measurably affected by glucose feeding. During superfusion with Tyrode solution, lowering the temperature from 35.5 degrees C to 15.5 degrees C led to a fast Vm decrease of roughly 2mV followed by an increase of 1-3mV. At the same time, aNai increased from 12.8 to 18.2mM within 10 min. Superfusion with EC solution for 10 min caused comparable changes in fed and fasted pigs. Vm depolarized at either temperature by about 16mV. At 35.5 degrees C the initial aNai of 17.5mM was roughly halved, whereas at 15.5 degrees C it decreased from 21.0 to 14.3mM. The results suggest that the nutritional state markedly affects the electric properties of liver. However, the effect on membrane potential of high-potassium organ-protective solutions seems to be distinctly more pronounced. Moreover, cellular Na+ activity decreases in consequence of an extracellular Na+ reduction with protective solutions, which might be balanced to some extent by a simultaneous temperature decrease. PMID- 1925067 TI - Involvement of oxygen in harvesting injury of the liver. An experimental study including substrate free organ persufflation to evaluate a specific therapeutic approach. AB - The present study was undertaken to assess the role of oxygen free radicals relating to cell damage upon reoxygenation of the ischemically altered isolated rat liver. Livers were excised and flushed via the portal vein with Ringer's solution and Euro-Collins solution, to which superoxide dismutase (SOD) was added in the experimental group. After warm ischemia at 37 degrees C and cold storage at 4 degrees C, the livers were reperfused via the portal vein with carbogen saturated Krebs-Henseleit solution. Other livers were subjected to a retrograde persufflation via the infrahepatic caval vein with either oxygen or nitrogen and then rinsed with Ringer's solution. During reperfusion, SOD-treated livers showed markedly reduced vascular resistance, lower enzyme release and enhanced VO2 accordingly, energy charge at the end of reperfusion was significantly higher in the treated group. With reference to the tissue content of malondialdehyde, SOD treated livers showed significantly less damage than the corroboration for these data. Enzyme activities in the eluate were significantly reduced under anoxic conditions as well as in the presence of SOD. We conclude from these data that oxygen free radicals do exert a detrimental impact on the reoxygenated liver, which could be specifically suppressed by application of exogenous SOD. PMID- 1925068 TI - Interleukin 1 production by human monocytes induced in culture with K562 cells. AB - The effect of neoplastic cells, K562, was evaluated on interleukin 1 (IL-1) production by peripheral blood monocytes of healthy humans. Secretion of the monokine was compared with that resulting from stimulation with bacterial lipopolysaccharide (LPS) or iron particles. In parallel, ability of non-malignant cells to induce production of monocyte-derived IL-1 was tested using allogeneic leukocytes (PBL). The studies were performed using concanavalin A (Con A) thymocyte co-activation assay, applying colorimetric assay of proliferation. The results obtained showed that IL-1 secretion by monocytes took place not only after tumor-cell stimulation, but also in co-cultures with allogeneic PBL. LPS and iron particles, however, were more efficient in stimulating IL-1 production. Absence of IL-1 activity was noted in supernatants of monocyte cultures in the presence of dexamethasone. Supernatants showing IL-1 activity were inactive in the presence of soluble immune response suppressor (SIRS) in IL-1 assay. PMID- 1925069 TI - Differences in glutathione status and lipid peroxidation of red and white muscles: alterations following ischemia and reperfusion. AB - Glutathione status and products from lipid peroxidation [measured as thiobarbituric acid reactive substances (TBARS)] were determined in red and white muscle tissue of the rat. Marked differences between both muscle types were found in reduced glutathione (GSH) and oxidized glutathione (GSSG) content, exhibiting 163% and 183%, respectively, higher levels in red than in white muscle tissue, while the ratio of GSSG/GSH showed no differences. These characteristics may be due to an adaptive mechanism related to the 48% higher baseline level of TBARS in red muscle tissue. Immediately after 4 h of tourniquet-ischemia GSH, GSSG, and TBARS were increased (16%, 32%, 45% in white muscle; 19%, 49%, and 42% in red muscle, respectively), whereas the GSSG/GSH ratio remained unchanged. During the subsequent reperfusion period, GSH decreased within 2 h by 39% in white and 89% in red muscle to a minimal level of 5 mmol/g protein in both types of muscle. No recovery from the depletion was observed up to 12 h of reperfusion. The GSH decrease was parallelled by a marked increase of the GSSG/GSH ratio (150% in white and 450% in red muscle) and followed by about 150% increase in TBARS in both muscle types. This suggests that the increase in damaging TBARS is a secondary event after depletion of cellular antioxidants. Treatment of the animals during the reperfusion period with methyl-prednisolone, deferoxamine, or superoxide dismutase and catalase did not prevent the GSH decrease, but were effective in reducing the GSSG/GSH ratio to near normal and reducing the TBARS increase by about 50%. PMID- 1925070 TI - Interstitial and cerebrospinal fluid levels of energy-related metabolites after middle cerebral artery occlusion in rats. AB - This investigation was designed to study the dynamics of energy-related metabolites (i.e., lactate, pyruvate, inosine, and hypoxanthine) in the extracellular fluid (ECF) of the striatum and in cisternal cerebrospinal fluid (CSF) during the first 6 h after middle cerebral artery occlusion (MCAO) using microdialysis. Ischemia induced a dramatic increase in the ECF levels of lactate, inosine, and hypoxanthine, while pyruvate did not change significantly. The major part of these changes occurred during the first 10 min after MCAO. Inosine tended to normalize towards the end, while lactate and hypoxanthine remained elevated throughout the experiment. There was no increase of the energy-related metabolites in CSF during the experiment. It was concluded that lactate, inosine, and hypoxanthine appear to be useful ECF markers of the compromised energy state of the brain during ischemia. Because the metabolites did not appear in CSF during the first 6 h after MCAO, such measurements seem not to be useful for early detection of a disturbance in energy metabolism. PMID- 1925071 TI - Risk factors for chronic bronchitis and chronic obstructive lung disease. AB - Among the risk factors for chronic bronchitis and chronic obstructive lung disease, only smoking and alpha 1-antitrypsin deficiency effects have been well demonstrated. Other factors, as air pollution, occupational exposure and childhood lung diseases may have an influence, but on a lower scale. The prevention of chronic bronchitis and chronic obstructive lung disease remains mainly based on antismoking programs. PMID- 1925072 TI - Bronchoalveolar clearance. AB - The lungs possess several mechanisms for cleansing themselves from locally produced biological debris and inhaled, deposited soluble and insoluble materials. Insoluble particles deposited on the conducting, ciliated airways will be primarily removed by mucociliary clearance, over a period of several hours, with cough acting as a back-up clearance mechanism. Insoluble particles deposited in the non-ciliated, alveolated regions of the lungs will be cleared primarily by the macrophages very slowly, with a biological half-life of several months. Soluble substances can pass through paracellular pathways and be cleared via the blood stream. PMID- 1925073 TI - Transplantation for end-stage lung disease. AB - The last decade has seen lung and heart-lung transplantation move from experimental procedures to clinical treatments. Innovative surgical techniques combined with the use of ciclosporin as an immunosuppressive agent have enabled successful transplantation in a wide range of end-stage lung diseases. Exclusion criteria for selecting recipients have relaxed, and improved preservation techniques have facilitated distant donor organ procurement and decreased peri operative mortality. A range of techniques for the physiological monitoring of the graft as well as diagnosis of major complications such as rejection and opportunistic infection have been introduced. Obliterative bronchiolitis remains a major challenge to the immunologist and to the chest physician in terms of etiology, pathogenesis and treatment. As survival rates improve with improved management, lung and heart-lung transplantations are contributing towards effective treatment of end-stage pulmonary disease as well as providing new insight into pulmonary physiology and into mechanisms of lung disease. PMID- 1925074 TI - Role of enzymes from inflammatory cells on airway submucosal gland secretion. AB - We examined the roles of enzymes from mast cells and from neutrophils in stimulating airway submucosal gland secretion. To avoid effects on surface epithelial cells and goblet cells, we studied a line of cultured bovine tracheal gland serous cells. We discovered that mast cell chymase and neutrophil elastase are the most potent secretagogues of airway submucosal glands described. Mast cell chymase markedly stimulated serous cell secretion in a concentration dependent fashion with a threshold of 10(-10) M, whereas tryptase had no effect. The response to 10(-8) M chymase (1,530 +/- 80% over baseline; mean +/- SEM) was approximately 10-fold higher than that evoked by other agonists such as histamine and isoproterenol. Both neutrophil proteases also stimulated secretion in a concentration-dependent fashion with a threshold of greater than 10(-10) M. Elastase was more potent than cathepsin G, causing a maximal secretory response of 1,810 +/- 60% over baseline at 10(-8) M. Secretion by the 3 proteases was noncytotoxic and required catalytically active enzymes. These findings suggest a potential role for neutrophil and mast cell proteases in the pathogenesis of increased and abnormal submucosal gland secretions in diseases associated with inflammation of the airways. PMID- 1925075 TI - Hyperreactivity and bronchial obstruction. AB - The main obstructive components in bronchial asthma and chronic obstructive pulmonary disease (COPD) are discussed. It is underscored that bronchospasm plays a significant role also in COPD, and that it merits specific treatment (beta 2 stimulants, antimuscarinics, theophylline) even when, in some cases, obstruction appears to be 'irreversible'. The majority of COPD patients react positively, although to a lower degree than asthmatics, not only to chemical agents (histamine, methacholine), but also to 'osmotic' stimuli, such as ultrasonically nebulized distilled water. Geometric factors seem to be in part responsible for the anomalous response. Considering the potent antireactive activity of bronchodilators (beta 2-stimulants in particular), this finding is a further indication for a regular bronchodilator treatment in COPD. Whether such a therapy serves also to improve the prognosis of COPD in the long run has not yet been established. PMID- 1925076 TI - Management of bronchial asthma. AB - The goals of the therapy of bronchial asthma are: (1) freedom from symptoms (within days); (2) normal spirometry (within weeks); (3) reduced or absent hyperreactivity and eosinophilia (within months), and (4) no airway inflammation = normal mucociliary clearance rate ('cured asthma'). Nobody knows how to cure asthma, but we know that we can reach at least stages 1 and 2 with consequent pharmacotherapy, and often also stages 3 and 4 by avoiding asthma-triggering agents and using long-term topical glucocorticoid therapy by inhalation. PMID- 1925077 TI - History of the treatment of chronic bronchitis. AB - Although chronic bronchitis was first named and described in 1808, the disease has been known since earliest time, and numerous drugs have been utilized in its therapy. The basic historic theories of human function have readily been applied to bronchitis; thus in Greek medicine, the disease was appreciated as one of excess phlegm. Early remedies included garlic, pepper, cinnamon, and turpentine, whereas later therapies of choice emphasized coffee, ipecac, and potassium nitrate. Most of the favored bronchodilator drugs of today are derived from the traditional folk remedies, ephedrine, atropine, and theophylline. The most interesting historical drugs, however, are those that have given rise to modern mucokinetic agents such as bromhexine and iodides. PMID- 1925078 TI - Chronic bronchitis in the 1990s: up-to-date treatment. AB - Prevention is the key to eradicating chronic bronchitis. Smoking is the prime factor involved. Quitting smoking is difficult even with modern aids such as counselling, filters, substitutes, hypnosis and acupuncture, and the success rate is only 20%. Passive smoking is also injurious. The role of atmospheric pollution is less well quantified. Other risk factors include lower social class, occupation, area of residence, housing, temperature, and childhood respiratory illness. Influenza vaccination gives 60-70% immunity. With exacerbations of chronic bronchitis, beta-lactamase-producing bacteria are important, though the overall need for antibiotics is uncertain judging by placebo-controlled studies. Inhaled beta 2-agonist bronchodilators may improve airflow obstruction, as may anticholinergic drugs (e.g. ipratropium), the two being additive. Oral theophyllines have a narrow therapeutic window, serious side-effects and only two thirds of the effect of beta 2-agonists. A corticosteroid trial for 2 weeks may relieve refractory airway obstruction in 17-23% of chronic bronchitis, to be followed by inhaled steroids. Mucolytic drugs remain controversial and are difficult to monitor successfully. Oxygen therapy may be indicated for hypoxic chronic bronchitis, including long-term usage in cor pulmonale. Pulmonary rehabilitation by exercise training has recently been appreciated, and may be used in combination with the above treatment modalities. PMID- 1925079 TI - Mucus pharmacology. AB - Until recently the experimental and clinical possibilities for investigation of the pharmacological effects of drugs acting on airway secretions were limited. Nowadays, new biological, physical and chemical techniques of investigation are applied to 'mucology', providing better characterization of this class of drugs. Experimental and clinical approaches are described. PMID- 1925080 TI - Long-term oxygen therapy for cor pulmonale in patients with chronic obstructive pulmonary disease. AB - Besides smoking cessation, antiobstructive therapy, and the treatment of intercurrent infections, long-term oxygen therapy has had the most impressive impact on survival in patients with chronic obstructive pulmonary disease (COPD). COPD leads to a functional and anatomical obstruction of the pulmonary vascular bed, with the development of pulmonary arterial hypertension and cor pulmonale. In these patients, survival benefit from long-term oxygen therapy (LTOT) stems mainly from improved hemodynamics. However, this improvement is limited: hypoxemic COPD patients treated by LTOT have the same life expectancy as nonhypoxemic COPD patients. Practical aspects concerning the prescription and application of LTOT are discussed, with special emphasis on ambulatory oxygen and oxygen-saving techniques. PMID- 1925081 TI - Chronic bronchitis: definition (or redefinition?). AB - Although a quite precise clinical definition was given to the term 'chronic bronchitis' in the early sixties, the terminology related to nonasthmatic, nonemphysematous obstructive airway disease remains a continuous source of confusion, as indicated by a recent international survey. Although histological studies point to the presence of widespread bronchial inflammation in this condition, preference should be given to simple and descriptive terminology in which the presence of airflow limitation is clearly and predominantly indicated, since it mostly affects prognosis. There would be no need to redefine 'chronic bronchitis', but simply replacing it by 'chronic mucus hypersecretion', to which it actually refers, would be the preferred solution. PMID- 1925082 TI - Lens and peripheral retinal relationships during vitrectomy. AB - Relationships between the posterior surface of the crystalline lens and instruments introduced into the vitreous cavity through pars plana incisions were evaluated in ten eyes from cadavers. Instruments were introduced 3.0 mm, 3.5 mm, and 4.0 mm posterior to the anterior part of the limbus. The distance between an instrument oriented toward the center of the vitreous cavity and the peripheral edge of the lens in that meridian was 1.6 mm when the sclerotomy was 3.0 mm from the limbus and 2.8 mm when the sclerotomy was 4.0 mm from the limbus. The arc length from the sclerotomy where the instrument was introduced to the most distal meridian of the ora serrata that could be reached without touching the lens ranged from 2.8 to 3.8 clock hours as the distance between the sclerotomy and the limbus increased from 3.0 mm to 4.0 mm. The distance between the ora serrata and the most peripherally accessible point on the retina in the meridian 180 degrees from the sclerotomy decreased from 6.0 mm to 3.1 mm as the distance between the limbus and the sclerotomy increased from 3.0 mm to 4.0 mm. PMID- 1925083 TI - Comparative study of clinical factors that predispose patients to proliferative vitreoretinopathy in aphakia. AB - To clarify the risk factors of proliferative vitreoretinopathy (PVR) in aphakia, the clinical features of 25 aphakic eyes with PVR were statistically analyzed and compared with a control group of 157 aphakic eyes with non-PVR rhegmatogenous retinal detachment. The statistically significant (P less than 0.05) factors that predisposed patients to PVR in aphakia were as follows: a history of vitreous loss on cataract surgery, retinal detachment developing within 3 months after cataract extraction, duration of retinal detachment longer than 3 months, break larger than three disc diameters, and choroidal detachment. Vitreous loss is believed to play the most important role in the development of PVR in aphakia. PMID- 1925084 TI - Dissection of epiciliary tissue to treat chronic hypotony after surgery for retinal detachment with proliferative vitreoretinopathy. AB - Surgery was performed on nine eyes of nine consecutive patients with chronic postoperative hypotony after prior vitreous surgery for retinal detachment and proliferative vitreoretinopathy. The operation included lysis of adhesions between the iris and the ciliary processes and removal of lens remnants and other fibrocellular tissue covering and/or causing traction on the pars plicata. The preoperative intraocular pressure was less than or equal to 5 mm Hg in all eyes, and the final postoperative intraocular pressure was 8 to 20 mm Hg in five eyes, 6 mm Hg in one eye, 4 mm Hg in one eye, and 0 mm Hg in two eyes. Minimum postoperative follow-up was 7 months and average follow-up was 10 months. This form of surgery to uncover and minimize traction on the ciliary body substantially increased the intraocular pressure in most of the treated cases and suggests that iridociliary adhesions and tissue proliferation covering and/or causing traction on the ciliary processes account for chronic postoperative hypotony in some cases after extensive surgery for proliferative vitreoretinopathy. PMID- 1925085 TI - External argon laser drainage of subretinal fluid using the endolaser probe. AB - The results of 200 consecutive scleral buckling procedures in which the argon endolaser probe was used to create a choroidotomy for drainage of subretinal fluid are reported. This technique was used in any case requiring drainage and was specifically employed in cases in which needle drainage was contraindicated because the detachment was shallow. The argon laser was set at 0.2 seconds, 1.25 watts, and was used with the endolaser probe held adjacent to, but not touching, the choroid. Drainage was successfully accomplished in 98% of cases. Rates of subretinal hemorrhage, retinal incarceration, and perforation related to laser drainage were 5.5%, 2.5%, and 1%, respectively. No large or submacular subretinal hemorrhages occurred. This technique appears to be particularly promising for drainage of shallow retinal detachments. PMID- 1925086 TI - A clinical comparison of the Oculab Tono-Pen with the Goldmann applanation tonometer in eyes filled with silicone oil. AB - Intraocular pressure in 21 eyes filled with silicone oil was measured with two different instruments: the Oculab Tono-Pen and a Goldmann applanation tonometer mounted to a slit lamp biomicroscope. Intraocular pressure ranged from 2 mmHg to 28 mmHg, and the mean difference between readings obtained from the two instruments was 0.64, which was not statistically significant. These results suggest that the Oculab Tono-Pen is an effective instrument with which to measure intraocular pressure in silicone-filled eye. PMID- 1925087 TI - Magnetic resonance imaging in choroidal osteoma. AB - High resolution magnetic resonance imaging (MRI) with surface coil and contrast material was used to demonstrate the presence of bone in choroidal osteoma. Contrary to initial impressions, choroidal osteoma does not show typical negative image of the bone in MRI scans. The ossifying tumor of the choroid appears as a bright (hyperintense) signal on T1-weighted images and as an area of relative low intensity on T2-weighted images. On contrast T1-weighted scans, the tumor showed gadolinium-DPTA (Gd-DPTA) enhancement. These MRI findings are discussed in relation with histopathologic features of choroidal osteoma and the presence of fat marrow in the intertrabecular spaces of the bone at the level of the choroid. PMID- 1925088 TI - Argon laser photoablation of a choroidal osteoma. AB - Choroidal osteomas are rare, juxtapapillary choroidal tumors, which are usually unilateral but can be bilateral in as many as 30% of patients. Choroidal neovascularization may complicate this condition and be associated with severe visual loss. A patient treated with argon laser photocoagulation for SRNVM is described, and clinical and radiographic evidence of destruction of the osteoma during an 8-year follow-up is presented. The possible mechanisms of laser's ablative effect on bone, in addition to clinical application for choroidal osteoma treatment, are discussed. PMID- 1925089 TI - Linear streaks in multifocal choroiditis and panuveitis. AB - The clinical differentiation between multifocal choroiditis and panuveitis (MCP) and the presumed ocular histoplasmosis syndrome (POHS) can be difficult. Each condition is associated with peripapillary atrophy, chorioretinal spots, and subretinal neovascularization. Peripheral chorioretinal streaks have been described as the "fourth sign" of POHS. A consecutive series of patients with MCP were examined to determine the prevalence of peripheral chorioretinal streaks. Examination of 47 involved eyes in 25 patients revealed three eyes with streaks near the equator. These findings suggest that the presence of peripheral linear streaks cannot be used to differentiate the POHS from MCP. PMID- 1925090 TI - Differential diagnosis of retinoblastoma. AB - Retinoblastoma is a malignant intraocular tumor of childhood that requires accurate diagnosis and prompt treatment. It is well known that several other ocular conditions of childhood can clinically simulate retinoblastoma. Knowledge of the clinical features that serve to differentiate retinoblastoma from simulating lesions may assist the clinician in arriving at the correct diagnosis and preventing misdirected therapy. This review provides a simple classification of those pseudoretinoblastomas and reviews the recent literature on this subject. It emphasizes the clinical features that help differentiate pseudoretinoblastomas from true retinoblastoma. PMID- 1925091 TI - Subretinal endophotocoagulation. A new model of subretinal neovascularization in the rabbit. AB - The disciform response of age-related macular degeneration and other diseases is determined by the development of subretinal neovascularization (SRN). Experimental animal models of SRN based on disruption of Bruch's membrane have been studied extensively during the past decade. Argon laser photocoagulation induced SRN in primates is one such model, but this is associated with extensive retinal damage. Because the injured retina could be angiogenic, and is not present in clinical SRN, this model might be more relevant if this factor could be eliminated. The current study was conducted with the primary aim of producing a rabbit model of SRN that minimizes retinal damage. Argon laser endophotocoagulation was applied beneath the retina of albino rabbits to achieve this goal. Although argon photocoagulation does not cause clinically apparent SRN (i.e., associated with leaking and pooling of fluorescein) in the rabbit, all laser lesions produced in the current study contained microscopic SRN. A rabbit SRN model would be highly desirable as a step toward other animal models, perhaps involving nonhuman primates, which might ultimately be clinically more relevant. PMID- 1925092 TI - Tissue plasminogen activator treatment of experimental subretinal hemorrhage. AB - Previous investigators have suggested that subretinal blood damages the retina in part because of its solid fibrin meshwork. The role of fibrinolysis in facilitating the clearance of subretinal hemorrhage and preventing degeneration of the overlying retina was studied. Autologous whole blood (0.1 ml) was injected into the subretinal space of 20 rabbits. Twenty-four hours later, the animals were randomized to subretinal treatment with 2.5 micrograms of tissue plasminogen activator or a similar volume of physiologic saline. Mean subretinal hemorrhage thickness 3 days after treatment had decreased to 42% of pretreatment thickness in treated eyes and remained unchanged in control eyes (P less than 0.0005). By 7 days mean clot thickness was 9% in treated eyes and 60% in controls (P = 0.005). Light microscopy revealed severe progressive retinal degeneration in both groups. No histologic evidence of retinal toxicity was found in cat retina after subretinal injection of tissue plasminogen activator (50 micrograms/ml). Although treatment with tissue plasminogen activator accelerated the clearance of subretinal hemorrhage, it failed to prevent secondary retinal degeneration in this rabbit model. PMID- 1925093 TI - Experimental retinal tolerance to emulsified silicone oil. AB - Vitreous replacement by silicone oil has become increasingly popular in the treatment of severe and complicated retinal detachment. Several studies have suggested that silicone oil may be toxic to the retina or may stimulate periretinal proliferation. To better understand its effects, emulsified or nonemulsified silicone oil was injected into rabbit eyes that had undergone mechanical vitrectomy. Silicone oil was labeled with phthalocyanine blue to aid in histologic localization. Retinal changes were compared by light microscopy at 1, 4, and 12 weeks after intraocular injection. Emulsified silicone oil was found to penetrate the inner retina at 1 week and cause epiretinal membrane formation as early as 4 weeks after injection. Nonemulsified oil produced no histologic changes in the retina. No cytotoxic effects were observed in eyes treated with ether emulsified or nonemulsified silicone oil. It is concluded that emulsified silicone oil can both penetrate the retina and stimulate epiretinal membrane formation in the vitrectomized rabbit eye. PMID- 1925094 TI - Silicone oil is an effective long-term tamponade after pars plana vitrectomy for complicated retinal detachments. PMID- 1925095 TI - [Topics of pulmonary nuclear medicine]. PMID- 1925096 TI - [Treatment with inhalation anesthetics for status asthmaticus]. PMID- 1925097 TI - [123I-metaiodobenzylguanidine myocardial images for assessment of sympathetic nervous system in the heart]. PMID- 1925098 TI - [Frequency characteristics in amplitude and phase lag of the catheter-manometer system]. PMID- 1925099 TI - [Treadmill exercise test in patients with hypertrophic cardiomyopathy with and without coronary artery disease]. AB - We studied whether the treadmill exercise test can discriminate between normal and significant narrowing of coronary arteries in patients with hypertrophic cardiomyopathy (HCM) accompanied with chest pain, and we compared the extent of myocardial ischemia during exercise. Thirty one patients with HCM were divided into two groups; 21 with normal coronary arteries and 11 with significant narrowing of coronary arteries. The treadmill exercise test was carried out in both groups. The following parameters were more frequently seen in the group with coronary stenosis. (1) short treadmill time (338, sec vs 542, p less than 0.05). (2) delta SBP less than or equal to 60 mmHg (delta: end point minus rest, 10 cases vs 12, 0.05 less than p less than 0.1). (3) significant delta ST depression (0.17 mV vs 0.05, p less than 0.05). (4) large delta ST/delta HR (3.3 microV.min/beats vs 0.7). delta ST/delta HR greater than or equal to 2.0 was the most useful for differentiating the two groups, and it was 90% in index both sensitivity and specificity for diagnosis of HCM with significant narrowing of the coronary arteries. It was concluded that treadmill exercise induced more severe myocardial ischemia in patients with HCM who had significant narrowing of the coronary arteries than in patients with HCM who had angiographically normal coronary arteries. The delta ST/delta HR was the most useful index for diagnosis of HCM with significant narrowing of the coronary arteries. PMID- 1925100 TI - [Assessment of denervated but viable myocardium in patients with myocardial infarction--by myocardial imaging with 201Tl and 123I-MIBG]. AB - The present study assessed sympathetic function in viable infarcted areas of the myocardium following the onset of myocardial infarction. The subjects were 19 patients with myocardial infarction. After exercise on a bicycle ergometer, simultaneous SPECT with Tl-201 and I-123 MIBG was performed. The behavior of MIBG following exercise remains to be clarified, but in the present study MIBG provided images different from those obtained with Tl. While the redistribution of Tl in the infarcted area was observed in 8 of 19 patients, MIBG was absent in the infarcted area in both the initial and delayed scans. In the patient undergoing CABG, the infarcted area showed no MIBG despite the normal perfusion of Tl. The previous proposal that the redistribution of Tl indicates myocardial viability to some extent suggests that the sympathetic function of the area of the myocardium showing the redistribution of Tl decreases even though the area is viable. These findings indicate that after the onset of myocardial infarction, there is a denervated but viable area in the myocardium, despite the viability demonstrated by Tl imaging. They also indicate that concurrent myocardial imaging with MIBG is useful for the detection of such a myocardium. PMID- 1925101 TI - [Late postoperative pulmonary vascular resistance in patients with tetralogy of Fallot and pulmonary atresia]. AB - Twenty-two patients with tetralogy of Fallot and pulmonary atresia underwent cardiac catheterization and angiocardiography late after repair. In ten patients, the disease was not associated with the major aortopulmonary collateral artery (MAPCA), but in 12 patients, the disease was associated with it. Three patients died after restudy, two because of pulmonary hypertension and one because of pneumonia. Pulmonary artery mean pressure was 15-92 (28 +/- 21) mmHg, being higher in 75% of the patients with MAPCA than the normal range. The number of pulmonary artery subsegments connected to the central pulmonary arteries was determined from pulmonary arteriography, being 22-42 (38 +/- 6). Pulmonary artery mean pressure and pulmonary vasculature resistance (PVR), 0.8-35.2 (10 +/- 9), inversely correlated with the number of the centrally connected pulmonary artery subsegments (r = -0.81, p less than 0.001 vs PAP, r = -0.85, p less than 0.001 vs PVR). PVR per subsegment also inversely correlated with them (r = -0.81, p less than 0.001). These findings suggest that pulmonary vasculature resistance is abnormally high in this disease, and increase as the number of the centrally connected pulmonary artery subsegments decrease. PMID- 1925102 TI - [An experimental study on the alteration of myocardial tissue by radiofrequency catheter ablation: differences according to the frequency and the device]. AB - To evaluate the alteration of myocardial tissue by radiofrequency (RF) catheter ablation according to differences of the frequency and the device, we applied RF catheter ablation to canine right ventricular myocardium in vitro. The devices delivering RF energy were LL-49(0. 49MHz, fixed voltage mode), RA-50 (13.56MHz, fixed watt mode) and HAT200 (0.52MHz, fixed watt mode with the capability of temperature adjustment). After RF catheter ablation were performed with a unipolar electrode catheter at various output under the same condition of contact, the ablated lesions by each device were compared. Histologically, we recognized coagulation layer with the necrosis of endocardium and the dissociation of myocardium in each experiment. The degree and the size of ablation layer was significantly larger in lower frequency delivery (p less than 0.05) and was significantly smaller by using the device with temperature adjustment as compared with the others (p less than 0.05). It was suggested that the alteration of myocardial tissue ablated with RF energy differ according to the frequency and the mode of output adjustment of the device. PMID- 1925103 TI - [Effects of antianginal drugs on left ventricular diastolic filling in patients with ischemic heart disease]. AB - To study the acute effects of isosorbide dinitrate (ISDN), nifedipine, propranolol and placebo on left ventricular diastolic filling in patients with myocardial ischemia, we repetitively performed exercise radionuclide angiography (RNA) following random assignment of each drug in 12 patients with effort angina pectoris, and 5 normal controls. Left ventricular time activity curves were constructed using computer technique. We obtained changes of hemodynamic parameters such as endodiastolic volume, systemic vascular resistance and ejection fraction. The peak filling rate (PFR), and filling rate in the first third of the diastolic period (1/3 FR) were used as the indexes of LV diastolic filling. 1/3 FR remained unchanged during peak exercise by the patients, while it increased significantly in normal controls. After administration of ISDN and nifedipine, 1/3 FR increased significantly during peak exercise by the patients. Especially after nifedipine, 1/3 FR improved significantly compared with the improvement after ISDN, although these two drugs had the same effects on systolic function. These findings showed that 1/3 FR was reliable as an indicator of LV diastolic filling in ischemic heart disease, and nifedipine improved LV diastolic filling not only by improving ischemic changes in myocardium but also by it's direct effect on left ventricular relaxation. PMID- 1925104 TI - [Clinical course and prognosis in SLE patients with pulmonary hypertension: a comparative study with primary pulmonary hypertension]. AB - Recently pulmonary hypertension (PH) has been recognized as one of life threatening complications which determine the prognosis of patients with systemic lupus erythematosus (SLE). Clinical aspects and pathology in patients with SLE complicated by PH (SLE-PH) have been reported to have a close similarity to those in patients with primary pulmonary hypertension (PPH), the prognosis of which is very poor in general. However, the long-term prognosis for patients with SLE-PH is not clear yet. Mainly because of some technical limitations for determining the severity of the PH, long-term follow-up studies have been inconclusive. In this study, 7 patients with SLE-PH and 6 patients with PPH were studied by using two-dimensional echocardiography. The interventricular septal curvature (R) was measured from the parasternal short axis view and the reciprocal value (1/R) was applied as a severity index of the PH. In 4 patients with SLE-PH and 6 with PPH, pulmonary arterial pressure was measured by cardiac catheterization concomitantly. There were no significant differences in 1/R and pulmonary arterial pressure between the two groups when PH was diagnosed for the first time. In the PPH group, the mean period of follow-up study was 25.3 months and all of the patients died during that period. In SLE-PH group, the mean period of follow-up study was 50.6 months, and only 3 patients (43%) died during that period. No patients in the PPH group showed improvement in 1/R, but 3 patients with SLE-PH improved in 1/R during a long follow-up period (60, 96 and 103 months respectively). Thus, the prognosis for SLE-PH was better than that for PPH, and there were some differences in the course and worsening behavior of PH in SLE-PH compared with that in PPH during the long-term follow-up study with reference to the echocardiographic investigation using 1/R value. PMID- 1925105 TI - [Prognostic implications of exercise induced silent myocardial ischemia in patients with angina pectoris]. AB - To clarify the prognostic implications of exercise induced silent myocardial ischemia (SMI) in patients with angina pectoris, the clinical characteristics and long-term prognosis after coronary angiography in 379 patients without prior myocardial infarction were investigated. According to the results of treadmill testing and/or Tl-201 exercise imaging after medical treatment, 50 patients with negative for ischemia were classified as control group, 110 patients with exercise induced SMI were classified as the SMI group, and 187 patients with painful ischemia formed the PI group. Thirty-two patients were excluded because of inconclusive exercise results. Single vessel disease and vasospastic angina were more frequent in the control group than in the SMI and PI groups. But there were no differences in baseline characteristics and extent of coronary lesions between the latter two groups. Heart rate, systolic blood pressure and rate pressure product at end point in treadmill testing were higher in the control and SMI groups than in the PI group. The mean follow-up period was 4.8 years, and follow-up was completed in every case. Cardiac events, including cardiac death, nonfatal myocardial infarction and readmission from severe angina, occurred in 25 patients of the SMI group, 43 of the PI group and 7 of the control group. Cumulative cardiac event curves did not show any statistically significant difference between the SMI and PI groups. We conclude the presence or absence of angina during exercise test is no longer the principal prognostic index for determining a patient's risk of cardiac events. PMID- 1925106 TI - [A case of left coronary ostial obstruction due to syphilitic aortitis]. AB - Coronary ostial stenosis is a rare lesion, which is a complication of syphilitic aortitis, Takayasu's aortitis, aortic valve disease, and familial hypercholesterolemia. We present a case of left coronary ostial obstruction due to syphilitic aortitis. A 67 years old man was admitted to our hospital for evaluation of a ten year history of angina on exertion. On physical examination, the only abnormal finding was a grade 2/6 high-pitched diastolic murmur. Coronary risk factor was not detected from biochemical results, but both the TPHA and FTA ABS test were positive. Treadmill stress test showed more than 2 mm ST segment depression associated with chest pain. Coronary angiography revealed complete obstruction of left coronary ostium with good collaterals from the right coronary artery. The coronary arterial tree was otherwise normal. Furthermore, aortagraphy showed a moderate degree of aortic regurgitation. From the examination of previous reports including our own case, we think that the angiographic features of syphilitic coronary ostial stenosis can be summarized as below. 1. Coronary artery stenosis is generally limited to the ostium. 2. The grade of stenosis almost always shows more than 90% stenosis, and sometimes bilateral coronary ostium can be affected. 3. Aortic regurgitation is frequently noted, associated with coronary ostial stenosis. PMID- 1925107 TI - [A case of hypertrophic cardiomyopathy with progressive cavity dilatation--a review of serial 201Tl myocardial imaging]. AB - We reviewed 201Tl images of a 32 year old man with dilated hypertrophic cardiomyopathy (DHCM). At 22 years of age, when he was diagnosed as having nonobstructive hypertrophic cardiomyopathy (HCM)IVST; 20mm, Dd; 44mm, EF; 62%), 201Tl images showed only a small defect in the anteroseptal segment. At 27 years of age, when he had the first cardiac symptom as palpitation on exertion, his perfusion defect of 201Tl became wider. At 32 years age, he was hospitalized because of deterioration of congestive heart failure. Echocardiography revealed left ventricular wall thinning(IVST; 6mm), left ventricular cavity enlargement (Dd; 63mm) with a large mural thrombus and reduced left ventricular ejection fraction (EF; 32%). Thus 201Tl images may provide useful information on the process of DHCM from HCM. PMID- 1925108 TI - The effects of D/Q and D/VA inequalities on pulmonary oxygen diffusing capacity estimates. AB - Bohr-integrated estimates of steady-state pulmonary diffusing capacity for oxygen (DLO2) were calculated using lung compartments with different VA/Q ratios. Compartmental diffusing capacity was distributed in proportion to either ventilation or blood flow. This method was applied to 115 gas exchange data sets previously collected from healthy human subjects during normoxic (PIO2 = 148 Torr) or acute hypoxic (PIO2 = 80 Torr) exercise. Ventilation-weighted estimates of oxygen diffusing capacity exceeded blood flow-weighted estimates by 10 and 78% during hypoxia and normoxia, respectively. While blood flow-weighted DLO2 estimates during heavy exercise were greater in hypoxia than in normoxia (mean +/ SEM of 87.1 +/- 4.4 vs 53.0 +/- 3.1 ml.min-1.Torr-1), ventilation-weighted estimates were not significantly different (93.2 +/- 5.5 vs 96.3 +/- 9.4 ml.min 1.Torr-1). These results show that the effect of D/Q inequality on DLO2 estimates is greater at higher levels of inspired oxygen. Furthermore, a D/Q mismatch of similar magnitude as the VA/Q mismatch that is observed during heavy exercise can account for a previously observed discrepancy between normoxic and hypoxic oxygen diffusing capacity estimates. PMID- 1925109 TI - Pressure profiles show features essential to aerodynamic valving in geese. AB - Inspiratory airflow in the avian lung completely bypasses the most cranial secondary bronchi (the ventrobronchi), and instead enters bronchi arising more caudally (the dorsobronchi). Dotterweich (1936) proposed that 'aerodynamic valves' prevented entry into the ventrobronchi. We have recently provided evidence that inspiratory aerodynamic valving in avian lungs depends on convective inertia in the primary bronchus (Banzett et al., 1987). Theoretical and physical models (Butler et al., 1988; Wang et al., 1988) showed that convective inertia could effect valving, but the effectiveness of valving at resting flows was less than that observed in the bird. This leads us to hypothesize that a segment of the primary bronchus is constricted, accelerating the gas and enhancing the convective inertia. To test this hypothesis in the present work we measured pressures throughout the airways and air sacs in anesthetized, pump-ventilated geese at different flow rates and gas densities. Our data show: (1) there is a large pressure drop in the primary bronchus close to the ventrobronchial junction, indicating the presence of a constriction; (2) this pressure drop increases with gas density and flow; (3) the convective inertia at this site is more than 10 times downstream opposing pressures. We conclude that the primary bronchus just cranial to the first ventrobronchus forms a constriction which accelerates inspired air. Furthermore, we conclude that the convective inertia of gas leaving this segment is sufficient to achieve inspiratory valving. PMID- 1925110 TI - Responses of upper airway muscles to gastrocnemius muscle contraction in dogs. AB - We studied electromyographic (EMG) responses of the alae nasi (AN) and the posterior cricoarytenoid (PCA) muscles, which act as upper airway dilators, during contraction of gastrocnemius muscle in six chest-intact anesthetized dogs with spontaneous breathing and in four thoracotomized, phrenicotomized and mechanically ventilated dogs with right thoracic and left cervical vagotomy. Muscle contraction was phasically induced by electrical stimulation of the intact gastrocnemius nerve or the distal cut end of this nerve for 20-30 sec. Stimulation intensity was determined as twice the motor threshold in each dog. In chest-intact animals, phasic contraction induced by intact nerve stimulation produced initial rapid increases in upper airway muscle activity, but stimulation of the distal cut end of the nerve did not show the rapid increase in upper airway muscle activity. Furthermore, stimulation of the proximal cut end did not produce any transient response with the stimulation intensity used in this study. In chest-open and vagotomized animals with artificial ventilation, responses of the upper airway muscles to contraction during the intact nerve stimulation were observed. These results suggest that the contraction of the gastrocnemius muscle activates upper airway dilating muscles via reflex mechanisms. PMID- 1925111 TI - Volume detection during voluntary and passive breathing. AB - The ability to detect small changes in tidal volume (VT) during either volitional or passive breathing was compared in seven normal subjects. Passive breathing was achieved with positive pressure applied at the mouth by a ventilator. Although baseline breathing pattern was similar for each subject during the two types of breathing, the ability of the subjects to detect changes in VT was at least as good, and in general better, during passive as compared to volitional breathing. This suggests that the generation of a motor cortical command to inspire and the resultant respiratory muscle contraction are not essential to the perception of a change in lung volume. An increase in information from receptors in the mouth, pharynx and extrathoracic airways sensitive to positive pressure may be responsible for the increased ability of most subjects to detect changes in VT during passive breathing. PMID- 1925112 TI - Effect of pentobarbital on spontaneous recovery from hypoxic apnoea in mice. AB - The effect of pentobarbital anaesthesia on spontaneous recovery from hypoxic apnoea (autoresuscitation) was investigated in SWR/J mice. Experiments were performed in 17 to 23 day old animals, in which the mechanism often fails, and in adults, in which it is usually successful. Mice, matched for age and weight, were injected with pentobarbital (62.5 mg/kg) or saline. Hypoxic apnoea was induced with 97% N2-3% CO2 and air given at its onset. To determine whether the effect of pentobarbital depended on hypothermia, we performed experiments in 17-23-day-olds with and without maintenance of body temperature. In the 'hypothermic' experiments one of 27 mice given pentobarbital died, compared with 10 of 22 controls (P less than 0.005). In the 'isothermic experiments', none of 15 mice given pentobarbital died, compared to 7 of 13 controls (P less than 0.005). All adults in both groups survived. Pentobarbital had a different effect on eupnoea and gasping: resting ventilation was depressed but gasp ventilation increased, and the duty cycle of gasps but not eupnoeic breaths was altered. Pentobarbital may facilitate autoresuscitation because gasping is unimpaired but oxygen consumption and lactate production are reduced, allowing cardiac function and cerebral survival until PO2 is restored. PMID- 1925113 TI - Effects of anoxia and graded acidosis on the levels of circulating catecholamines in turtles. AB - We measured circulating levels of catecholamines in painted turtles subjected to anoxia with different degrees of concomitant acidosis at 20 degrees C and in turtles subjected to long-term submergence at 3 and 10 degrees C. Blood levels of both epinephrine (E) and norepinephrine (NE) increased during N2-breathing, N2/CO2 breathing and submergence, with NE generally being present in higher concentrations than E. During submergence at 20 degrees C, anoxic turtles experienced an extreme acidosis and NE levels exceeded 18,000 pg/ml. The greater the degree of acidosis in anoxic turtles the higher were the levels of plasma NE (log [NE; pg/ml] = 1.640 x pHa + 15.776, r = -0.826). Elevation of plasma E under anoxic conditions was more modest and the correlation between plasma E and pHa was less pronounced (log [E; pg/ml] = -0.329 x pHa + 6.069, r = -0.285). Submergence at lower temperatures also resulted in increases in plasma levels of NE, but while plasma E generally increased during anoxia, this elevation was less dramatic than that observed for NE. Exposure of turtles to either mild (6.5% CO2) or severe (14.5% CO2) normoxic hypercapnia resulted in no increase in E and only modest increases in NE. Upon resumption of air-breathing in all of the 20 degrees C protocols, turtles rapidly restored E and NE to control levels. The function of elevated plasma catecholamines during anoxia and acidemia in turtles is unknown but may be important in stimulating respiratory and cardiovascular recovery once air-breathing is resumed. Catecholamines may also play a role in mediating the rise in blood glucose we observed in this study, which may be an important factor in maintaining tissue viability during anoxic stress. PMID- 1925114 TI - Tumor necrosis factor attenuates beta agonist-evoked Cl- secretion in canine tracheal epithelium. AB - We examined the effect of human recombinant TNF alpha on the potential difference (PD) and short circuit current (SCC) of canine tracheal epithelium using an Ussing chamber. Luminal or submucosal TNF (2 to 200 U/ml) produced no significant alterations in the basal PD or SCC values. Pretreatment with luminal TNF significantly reduced isoproterenol (ISOP, 10(-6) M)-evoked increases in SCC and PD to 57% and 66% of that with ISOP alone, respectively, with a significant decrease in conductance (G) to 87% of that with ISOP alone in a dose-dependent fashion, from 10 to 200 U/ml. Even after ISOP (10(-6) M)-evoked PD and SCC had reached a plateau, TNF produced significant decreases in PD and SCC up to 79% and 83% of that with ISOP alone, respectively, in a dose-dependent fashion, from 50 to 200 U/ml. Amiloride did not alter the inhibitory action of TNF on ISOP-evoked SCC and PD values. Antiserum against TNF abolished the inhibitory action of TNF on ISOP-evoked response. In contrast, submucosal TNF did not alter PD, SCC or G. These findings indicate that TNF attenuates beta agonist-evoked increases in chloride secretion across airway epithelium. PMID- 1925115 TI - Effect of induced acidosis on cytotoxicity of anticancer drugs. AB - The effect of adriamycin (ADR), vincristine (VCR), mitoxantrone (MTN) and cis platin (PtCl) at acidic pH on the incorporation of 3H-thymidine (3H-TdR) was studied in vitro on P388 murine leukemia cells. The incorporation was inhibited at low pH by the four drugs used. In order to induce acidosis in tumor bearing mice, 6 g/kg glucose was administered intraperitoneally. The lowest pH that could be obtained was 6.8 two hours after glucose administration. The drugs ADR, VCR, MTN and PtCl administered to tumor-bearing mice 2 h following induction of acidosis resulted in significant increase in the life span of the tumor bearing mice. PMID- 1925116 TI - A multi-modality approach for the treatment of AIDS. PMID- 1925117 TI - Extravasation of doxorubicin from vascular access devices. PMID- 1925118 TI - Suppression of tumor vascular activity by radioantibody therapy: implications for multiple cycle treatments. AB - Autoradiographic analysis of the intratumor location of radioiodinated Mu-9 anti CSAp antibody within 7 days of administration reveals a restricted distribution within 3-6 cell layers surrounding tumor vessels. Within 7-14 days after suboptimal radioantibody treatment (approximately 3000 rads), tumor vessel morphology and physiology are altered. Vessel number is reduced by 60-70%, vessel diameter is reduced, and remaining vessels are surrounded by fibrotic tissue. Vascular volume (VV) is reduced by 75%, blood flow rate (BF) is reduced 65%, and vascular permeability (VP) to an IgG is reduced by 60%. The change in VV is reversible by day 35 but BP and VP remain suppressed. Normal tissue (liver and lung) vasculature experience only small pertubations in physiology. These functional changes in tumor vessels reduce the magnitude of accretion of a second dose of radioantibody in tumor but not in normal tissue. PMID- 1925119 TI - Gastrointestinal pathology. PMID- 1925120 TI - Adenocarcinoma of the lower esophagus and the esophagogastric junction. AB - This report describes adenocarcinoma in patients with Barrett's esophagus (BE) and adenocarcinoma of the esophagogastric junction (EGJ) and the gastric cardia. Definitions, frequency, and general features of both conditions are described. The macroscopic features and microscopic findings are detailed for invasive adenocarcinoma and superficial (early) adenocarcinoma. Prognosis and follow-up are evaluated using flow cytometry as a factor of prognosis. Precancerous conditions and etiological factors are discussed. In addition, primary adenocarcinoma of the lower esophagus not associated with BE is considered. The precancerous lesions and precancerous markers in BE and in the cardia are examined, including type of dysplasia, histochemical study, and other lines of research. PMID- 1925121 TI - Gastritis and its relation to gastric carcinogenesis. AB - There have been rapid changes in understanding of chronic gastritis recently, fueled largely by the recognition of gastric infection by Helicobacter pylori. This report reviews the newer classifications of chronic gastritis, and describes the characteristics of H pylori-positive and -negative patterns of gastritis. The relevance of H pylori infection to gastric carcinogenesis is also discussed. PMID- 1925123 TI - Malignant lymphoma in the gastrointestinal tract. AB - The main function of gut-associated lymphoid tissue is to provide an adaptive protective mechanism to help defend the body from exogenous antigen. This complex function requires the coordination of various cellular elements, including B cells, T cells, macrophages, and the epithelial cells of the gut. The control of this remains poorly defined, but involves various cellular subpopulations, humoral factors acting by autocrine and paracrine means, and cell adhesion molecules regulating tissue tropisms. Disruption of these cybernetic mechanisms is likely to be fundamental to the development and behavior of gut lymphomas. Although conventional histopathology is likely to remain the mainstay of diagnosis and patient management, further advances in the understanding, diagnosis, and therapy of gut lymphomas will require a greater knowledge of the cells and molecules that regulate the lymphoid milieu of the gut. PMID- 1925122 TI - Epithelial and neuroendocrine tumors of the duodenum. AB - This review considers the pathologic features of epithelial tumors and tumor-like lesions of the duodenum and highlights potential pitfalls in their histological diagnosis. The tumor-like lesions include Brunner's gland hamartoma, myoepithelial hamartoma, and the mucosal polyps of the Peutz-Jeghers and juvenile polyposis syndromes. The true neoplasms are of two broad groups. The first includes duodenal adenomas and carcinomas, whose microscopic features, histogenetic relationships, and clinical significance closely mimic their commoner counterparts in the large intestine and which, when multiple, are closely associated with familial adenomatous polyposis coli. The second includes a number of uncommon endocrine cell tumors showing a great diversity of histological pattern, and which may be single or multiple. Among these are typical argyrophil carcinoids, which may secrete gastrin to give rise to the Zollinger-Ellison syndrome, and which may occur as part of the inherited multiple endocrine neoplasia syndrome type 1 (MEN-1); glandular somatostatin-rich, apparently nonargyrophil, carcinoids containing psammoma bodies that can be easily confused histologically with adenocarcinomas, and which are linked to type 1 neurofibromatosis (von Recklinghausen's disease) and phaeochromocytoma; and the gangliocytic paraganglioma, a rare tumor composed of neural elements, ganglion cells, and endocrine cells. Accurate histologic diagnosis of mucosal tumors and tumor-like lesions of the duodenum is important not only for immediate patient management, but also because it may provide the first clue to the existence of an inherited tumor syndrome, with its broader implications for the patient's family and potentially important consequences for genetic counseling. PMID- 1925124 TI - Newly recognized forms of colitis: collagenous colitis, microscopic (lymphocytic) colitis, and lymphoid follicular proctitis. AB - Based on pertinent data from the literature and on their personal experience, the authors present a clinicopathological review of collagenous colitis, microscopic (lymphocytic) colitis, and lymphoid follicular proctitis. The following aspects of these three newly recognized forms of colitis are emphasized: clinical features, light microscopy, histological diagnostic problems, immunological aspects, coexisting diseases, treatment, etiology, and pathogenesis. Special attention is paid to possible overlap between collagenous colitis and microscopic (lymphocytic) colitis. PMID- 1925125 TI - Psychic phenomena in partial seizures. PMID- 1925126 TI - Disorders of consciousness and associated complex behaviors. AB - Behavioral events during epileptic seizures, while varied, comprise only a portion of the total spectrum of human behavior. Studies using intensive video monitoring have permitted insight into the common and uncommon events in epileptic seizures. Comparison of data from these studies with data from other disorders, notably psychiatric disease, allows a more complete understanding of the nature of these disorders and of the differential diagnosis of each. Disorders in which consciousness is altered are common and heterogeneous; it is now possible to differentiate these various disorders. The information presented here provides a framework for the physician confronted with these diagnostic dilemmas. PMID- 1925127 TI - Unusual clinical manifestations of migraine and "the borderland of epilepsy"- reexplored. PMID- 1925128 TI - Sleep disorders and epilepsy: differential diagnosis. PMID- 1925129 TI - The symptoms of transient cerebral ischemic attacks. PMID- 1925131 TI - Personality in epilepsy. PMID- 1925130 TI - Episodic violence. PMID- 1925132 TI - Interictal cognitive changes in epilepsy. AB - There is little evidence for significant intellectual deterioration in well controlled seizure disorders. With recurrent convulsive seizures, the picture is less clear and depends on severity, type, age of onset, and frequency of toxic levels of antiepileptic drugs (see Table 1). In the interictal state, deficits in verbal language and memory have been observed, especially in patients with complex partial seizure foci in the left (dominant) hemisphere. The memory deficits appear to affect new learning and retention of material; the verbal deficits are more subtle, affecting word-finding, verbal fluency, and comprehension abilities. Both of these changes may either go unnoticed by the patient in day to day activities or be attributed to the effects of antiepileptic medication. Antiepileptic drugs can also affect interictal cognitive functioning. The worst of these appears to be phenobarbital; phenytoin has an intermediate effect; valproic acid and carbamazepine as single agents seem to produce fewer adverse effects. However, individual patients may be particularly sensitive to cognitive side effects of certain drugs. Finally, attention deficits and slowing of cognitive processes, either chronically or intermittently, appear to affect all seizure patients to some extent. The syndrome is more prominent in frontal or generalized seizure patterns. The intermittent nature of these disturbances has been emphasized in recent research on subclinical interictal spike-wave electrical phenomena. PMID- 1925133 TI - Psychopathology in epilepsy. AB - Although the majority of epileptics who are well controlled on medication do not show significant evidence of psychopathology, a subset of epileptics have serious psychiatric disturbances. Risk factors for the development of psychopathology appear to include poorly-controlled seizures, a long duration of seizure disorder with onset in childhood, seizure focus in the temporal lobe, bilateral or multiple discharges on EEG, and structural lesions. All of these factors appear to put the patient at greater risk of brain dysfunction, possibly because of the disruption of limbic functions associated with behavior and personality. The onset of seizures in childhood is likely to affect the development of personality and social functioning adversely. Although not a focus of this article, premorbid personality, psychologic reactions to having epilepsy, and the social problems accompanying the disease are likely to contribute greatly to the development of psychopathology. The development of psychiatric disorders in epilepsy thus appears to be a complex, multifactorial process. No single factor, such as seizure type, EEG findings, lateralization, pathology, or demographic variables is likely to be explanatory. Recent research has focused on accounting for many of these factors, and future investigations should shed further light on why some epileptics develop psychiatric problems and how best to treat these disorders. PMID- 1925134 TI - Depression in patients with epilepsy: an overview. PMID- 1925135 TI - Gower's sign. PMID- 1925136 TI - Motor phenomena of seizures. PMID- 1925137 TI - Somatosensory, special sensory, and autonomic phenomena in seizures. PMID- 1925138 TI - Women's perceptions of early detection in breast cancer: how are we doing? AB - Breast cancer is a significant risk to many women in the United States. It is also a major cause of death among American women. The National Cancer Institute's Year 2000 breast screening goal is to increase the percentage of women aged 50 to 70 years who have physical examination and mammography to 80%. However, many barriers to screening remain. Providing correct information and education regarding risk and mammography may help to overcome these barriers and achieve this goal. PMID- 1925139 TI - Local therapy for breast cancer: treatment choices and decision making. AB - Treatment options for the woman diagnosed with breast cancer have changed considerably over time. Mastectomy was standard treatment for breast cancer 5 years ago. Today, breast conservation treatment (excision of primary tumor plus radiation therapy) is appropriate therapy for the majority of women with stage I or II breast cancer. Women now have options for therapy and can play a major role in deciding their courses of cancer care. PMID- 1925140 TI - Reconstructive surgery in primary breast cancer treatment. AB - The goal of breast reconstruction is achievement of symmetry and preservation or restoration of a positive body image. The two methods of reconstructive breast surgery are implantation of a prosthesis or a flap procedure using skin, with or without autologous tissue from a donor site. Factors that determine which method is most appropriate are based on predicted outcome, patient expectations, and patient risk factors associated with complications of surgery. PMID- 1925141 TI - Breast cancer: psychosocial consequences for the patient. AB - Women with breast cancer experience various psychosocial problems throughout the continuum of the disease. The psychosocial impact and adjustment of women with breast cancer during the phases of pretreatment, primary treatment, adjuvant therapy, recurrence, and advanced disease have numerous implications for nursing practice and research. PMID- 1925142 TI - Psychologic consequences of breast cancer on partner and family. AB - Breast cancer can have psychologic consequences not only for patients but also for the entire family system. Research indicates a major impact on the husband, the marital relationship, the children, and family roles and responsibilities. Greater attention needs to be given to the family members to ensure that they get the support they need, and to enable them to maintain their supportive roles with the patient. PMID- 1925143 TI - Development of occupational health in Japan. AB - This paper was presented as a Lucas Lecture 1990 before the Faculty of Occupational Medicine, Royal College of Physicians, United Kingdom. It describes the development of occupational health in Japan including primitive industrialization (mining, smelting and others) back as far as the 8th century. The modern industrialization of Japan began slightly over one hundred years ago, i.e. from the beginning to the middle of the Meiji era. Before World War II, Japanese workers in industry suffered terrible working conditions, represented by a booklet published in 1925 entitled "The Tragic History of Female Workers" by Wakizo Hosoi. At that time a pioneer named Dr. Gito Teruoka was hard at work. He literally became the "Father of Occupational Health" in Japan. He established the Kurashiki Institute of Science of Labour in 1921 in Kurashiki City located in western Honshu, which is the main island of Japan. At the beginning of the Showa era, from 1930 to 1950, various types of occupational diseases were reported and the situation was overviewed by Dr. Juko Kubota. The rapid industrialization immediately after World War II during which workers were exposed to chromium, benzidine, beta 2-naphthylamine, arsenic, vinyl chloride monomer, asbestos, bischloromethyl ether and other chemicals gave rise to occupational cancer. The Ministry of Labour (MOL) was established in 1947 and the Labour Standard Law enacted. As a result, the incidence of tuberculosis decreased rapidly and occupational health emphasized the early detection of tuberculosis. After tuberculosis was nearly eradicated, more complicated working conditions developed in various industries. MOL enacted the Industrial Safety and Health Law in 1972 and occupational health practices improved greatly. Furthermore, in 1988 MOL amended the Law and announced guidelines on maintenance and promotion of health for the work population. However, there is a great disparity in occupational health services between large establishments and small factories. The University of Occupational and Environmental Health, Japan, (UOEH) was established in 1978 to promote occupational health sciences as well as to train and foster occupational health personnel to meet the short supply of occupational health physicians. However, there is no authority that establishes standards for occupational health physicians and nurses. The urgent necessity of establishing an authorized institution for the qualification of occupational health personnel is emphasized. PMID- 1925144 TI - Medical education at Mayo Clinic (Mayo Medical School). PMID- 1925145 TI - Detection of the breakthrough of organic solvent vapors on an activated carbon adsorption column using a gas detecting reagent. AB - A new adsorption device which is able to detect the breakthrough of organic solvent vapors was developed using a detecting reagent which is packed in a gas detector tube. The organic vapor which leaks from an activated carbon adsorption column reacts with the detecting reagent. The breakthrough is detected by the stain of the reagent. When the humidity of test air was zero, the reagent was stained sharply before the breakthrough was observed. However, in the case of using humid air, the color of the detecting reagent did not clearly change, even after the breakthrough had progressed considerably. PMID- 1925146 TI - [The necessity of motivation for acquiring the habit of exercise by means of a calorie counter combined with an accelerometer]. AB - The development of the habit of exercise is necessary for workers whose daily occupation prevents them from doing physical activities. However, few workers have acquired this habit of exercise. To motivate such workers, the validity of a calorie counter combined with an accelerometer (KENZ Calorie Counter or KENZ Calorie Counter alpha) was tested as a motivation tool for acquiring this habit. The subjects of this study were 14 volunteers. After 7 days' preliminary measurement of their physical activities by a calorie counter, they continued to measure the energy consumption of their physical activities over one month. Ten volunteers were able to continue the measurement, but 4 volunteers dropped out. The energy consumption of physical activities after one month measurement significantly (P less than 0.001) increased to 70% more than that of the preliminary measurement. At the present time, nine volunteers are continuing to measure their daily energy consumption. The results suggest that the measurement of one's daily physical activities by a calorie counter is one of the best ways to develop the habit of exercise. PMID- 1925147 TI - Dieulafoy's ulcer associated with the tortuous caliber persistent arteries: report of three cases. AB - Many papers have reported that Dieulafoy's ulcer is one of the notorious causes of gastric hemorrhage. Three cases of shallow subfundic ulcers with massive bleeding are reported. The resected specimens have demonstrated that elevated caliber-persistent artery (CPA), a branch of the left gastric artery with few anastomoses, in the base of the ulcer has tortuous penetration from the serosa to submucosa, showing patchy, eccentric intimal fibroelastosis. These findings of CPA are almost the same in both anterior and posterior walls, namely both the ruptured and contralateral sides. Thus, morphogenesis of the ulcer may have originated from anatomical deviation, which is related to regional hypertension aggravated by longterm peristalsis, as well as aging. PMID- 1925149 TI - [A survey of ethylene oxide sterilization in a hospital]. AB - The health and environmental problems of ethylene oxide gas sterilization in a hospital are reported. Eight nurses who had been engaged in the gas sterilization, sometimes operated the auto-sterilizer in an inadequate manner; they exposed more than several hundred ppm of ethylene oxide once or twice a week. The main acute effects on these nurses after massive exposure were headaches, general fatigue and irritation of the eyes and throat. But no signs of polyneuropathy were seen. This survey suggests that there is a great risk of ethylene oxide poisoning while sterilizing instruments in a hospital. PMID- 1925148 TI - [Supracondylar knee-ankle-foot orthosis for post-polio syndrome]. AB - We report a 69-year-old female suffering from post-polio syndrome. Though she experienced acute poliomyelitis at one year of age, she had been well until 67 years of age when she complained of muscle weakness and pain in her right lower extremity and gait disturbance. As she was admitted to our hospital for further evaluation and rehabilitation, we prescribed for her the rehabilitation program consisting of gait training with a supracondylar knee-ankle-foot orthosis, low load repetitive muscle strengthening exercises, and continuous stretching of her right knee joint after heat treatment. She regained a stable gait with the orthosis. We thought that the disuse and overuse of the lower extremities played a part in the onset of post-polio syndrome and that the rehabilitation including the low-load repetitive muscle strengthening exercises and gait training with a supracondylar knee-ankle-foot orthosis was effective against her disability. PMID- 1925150 TI - Mean square error of estimates of HIV prevalence and short-term AIDS projections derived by backcalculation. AB - We simulated multinomial AIDS incidence counts from 27 'representative' AIDS epidemics that spanned a period corresponding to previous applications of backcalculation (1 January 1977 to 1 July 1987) and assessed mean square error for several back-calculated estimators of HIV prevalence and short-term AIDS projections. Estimators were based on flexible model selection procedures that chose the best-fitting non-negatively constrained model of the infection curve from a family of possible step-function models. Selection of the best-fitting model from a family of four-step models each with a long last step of width of 4 or 4.5 years offered a favourable tradeoff between bias and variance when compared with selection from families of models with three steps or from families with a short last step. Five-step models performed as well as four-step models. Three-step models had substantially larger mean square error in some epidemic situations. Percentage root mean square error (PRMSE) for estimates of cumulative HIV prevalence as of 1 January 1985 was less than 14 per cent over a range of hypothetical epidemics of N = 50,000 infected individuals. PRMSE for short-term projections was less than 18 per cent. Estimates of cumulative HIV prevalence as of 1 July 1987 were substantially more uncertain and had a PRMSE of 33 per cent in the unfavourable case of a rapidly rising HIV epidemic. Estimates of cumulative HIV prevalence as of 1 July 1987 were positively biased in HIV epidemics with a rapidly decreasing recent HIV incidence rate and negatively biased in rapidly increasing HIV epidemics. Despite these uncertainties, we obtained useful estimates even for HIV epidemics with as few as 5000 infected individuals. PMID- 1925151 TI - Misclassification of covariates. AB - In the context of reported data on asthma mortality, we examine two types of covariate misclassification. The first type is non-differential misclassification, in which the proportion of subjects misclassified is invariant over exposure and disease status. Building on work by Cox and Elwood and by Blettner and Wahrendorf, we find that the range of admissible values for misclassification proportions is bounded by the observed data, and may not include any values that account for observed heterogeneity of effect estimates. The second type is differential misclassification, in which the classification error differs according to the disease or exposure classes to which study subjects belong. If the relation between exposure and the confounding variable or between the confounding variable and disease is strong, differential misclassification can produce large variations in the stratum-specific odds ratio estimates. PMID- 1925152 TI - Adjustment for non-differential misclassification error in the generalized linear model. AB - It is well known that estimates of association between an outcome variable and a set of categorical covariates, some of which are measured with misclassification, tend to be biased upon application of the usual methods of estimation that ignore the classification error. We propose a method to adjust for misclassification in covariates when one applies the generalized linear model. In the case where one can observe some true covariates only through surrogates, we combine a latent class analysis with the approach to incorporate multiple surrogates into the model. We include discussion on the efficacy of repeated measurements which one can view as a special case of multiple surrogates with identical distribution. We provide two examples to demonstrate the applicability of the method and the efficacy of multiple replicates for a covariate subject to misclassification in a regression framework. PMID- 1925153 TI - Validation techniques for logistic regression models. AB - This paper presents a comprehensive approach to the validation of logistic prediction models. It reviews measures of overall goodness-of-fit, and indices of calibration and refinement. Using a model-based approach developed by Cox, we adapt logistic regression diagnostic techniques for use in model validation. This allows identification of problematic predictor variables in the prediction model as well as influential observations in the validation data that adversely affect the fit of the model. In appropriate situations, recommendations are made for correction of models that provide poor fit. PMID- 1925154 TI - Statistical analysis of repeated events forming renewal processes. AB - For each of several individuals a sequence of repeated events, forming a renewal process, is observed up to some censoring time. The object is to estimate the average interevent time over the population of individuals as well as the variation of interevent times within and between individuals. Medical motivation comes from gastroenterology, and concerns the occurrence of certain cyclic movements in the small bowel during the fasting state. Two statistical models are considered: one is the standard variance component model adapted to censored data, and the other is a recent intensity based model with a random proportionality factor representing interindividual variation. These models are applied to the motility data, and their advantages are discussed. The intensity based model allows simple empirical Bayes estimation of the expected interevent times for an individual in the presence of censoring. PMID- 1925155 TI - An empirical Bayes formulation of cohort models in cancer epidemiology. AB - This paper concerns the incidence rates of malignant skin melanoma for several age-sex groups and time periods in three geographic regions, uses a method of cohort analysis and employs a two-stage random effects model. The first stage entails the assumption that the within-region variation in the frequency of disease incidence for a fixed age-sex-cohort group has a Poisson distribution with mean proportional to the population at risk. The second stage, after adjusting for age and sex, entails the assumption that the between-region geographic variation in the logarithm of the true incidence rate has a prior distribution with parameters estimated by the method of maximum likelihood. After adjusting for age effects, we estimate random geographic-specific cohort effects for each sex with use of an empirical Bayes method and compare the results with the usual multiplicative Poisson model that assumes fixed geographic-specific cohort effects for each sex. This comparison shows that the method presented here provides more stable estimates of geographic-specific cohort effects, and in addition the random effects model describes these data more adequately. PMID- 1925156 TI - Simple tests of homogeneity of controls in matched studies. AB - Consider matched case-control studies with a pair of distinguishable controls, say neighbourhood and hospital, wherein one of the controls may be missing. Liang and Stewart derive an efficient test for the possible difference in controls for the complete data case. They suggest inefficient tests for the situation where some triplets are incomplete. Levin, and Risch and Tibshirani, derive efficient tests for the incomplete triplet case by the methods of maximum likelihood estimator (Wald) tests and likelihood ratio tests, respectively. All these tests require the use of compute algorithms. Using score theory, we derive a simple efficient test for complete triplets which only requires solving a quadratic equation. Furthermore, we show that the usual normal approximation to McNemar's test is equivalent to the score test and is thus fully efficient as well. For incomplete triplets, score theory leads to a fully efficient test which only requires the solution of a cubic equation. We propose a nearly efficient test which is even more simply computed. The example of Liang and Stewart illustrates application of the results. PMID- 1925157 TI - Homogeneity of the relative risk in cohort studies. AB - We propose a statistical method to test the homogeneity of relative risk in cohort studies. We illustrate its application to an original data set from a low risk group of end-stage renal disease patients on haemodialysis. The use of the method is as a global test against the omnibus alternative. PMID- 1925158 TI - Exploring the order of odds ratios using the bootstrap. AB - We show the use of the bootstrap resampling method to examine further the order of a series of odds ratios. Specifically, the bootstrap provides a method for estimating the probabilities that one would find in subsequent independent samples from the same population the observed odds ratio rankings. To illustrate this use of the bootstrap, we modelled the responses of 77 white male physicians to an ethical dilemma involving hypothetical patients. Would the physician report positive HIV status to the health department or would he maintain patient confidentiality? To see if a patient's sex, race, or sexual preference would influence the physicians' decisions, each physician received one of eight randomly selected descriptions of a hypothetical patient. To evaluate the initial order of the patient categories, we constructed 1000 bootstrap samples. Black heterosexual males ranked first or second in 92.2 per cent of the bootstrap samples; black homosexual males ranked first, second or third in 88.6 per cent; and white homosexual females ranked sixth or seventh in 82.9 per cent. Thus we would expect to observe these rankings of the categories in a high percentage of subsequent independent samples. PMID- 1925159 TI - Estimating departure from normality. AB - Departure of a sample from a normal distribution should be assessed by a quantity that is meaningful in terms of the data, rather than merely by the P-value from a test statistic. Indices of departure based on the Shapiro-Francia W' and the Shapiro-Wilk W statistics are derived, and shown to have a natural interpretation in relation to the normal probability plot. A new diagnostic plot is proposed. An example is given which shows the relationship between one of the new indices and errors in calculated reference ranges due to non-normality of the data. PMID- 1925160 TI - Effect of regression to the mean in the presence of within-subject variability. AB - Regression to the mean arises often in statistical applications where the units chosen for study relate to some observed characteristic in the extreme of its distribution. Gardner and Heady attribute the effect of regression to the mean to measurement errors. They assume the model Yi = U + ei, where U is a fixed within subject component and ei is the random measurement error. They suggest several replicate measurements to reduce the regression effect under the assumption that the measurement errors ei are independent within subjects. While measurement errors play an important role in regression to the mean, one should not overlook within-subject variation. In this paper, we consider a model to estimate the regression effect in the presence of correlated within-subject effects as well as independent measurement errors. PMID- 1925161 TI - Estimating kappa from binocular data. AB - A common error in statistical analysis of ophthalmic data is the lack of accounting for the positive correlation generally present between observations made in fellow eyes. The alternative of data analysis from only one eye in each patient may lead to loss of power and unrealistically large confidence intervals. This paper discusses a method to estimate kappa, a measure of agreement between two graders, when both graders rate the same set of pairs of eyes. The method assumes that the true left-eye and right-eye kappa values are equal and makes use of the correlated binocular data to estimate confidence intervals for the common kappa. Simulations show that the new estimators are better than the estimator based on only one eye; new confidence intervals had the correct coverage probability, but were usually only about 70 per cent as wide as single-eye intervals. The general methodology described here applies to analysis of grader agreement in rating other paired body structures. PMID- 1925162 TI - A possible source of error in calculating median age at first occurrence of an event from a cumulative distribution of reported ages. PMID- 1925163 TI - Contradictory correlations between derived scales. AB - In a clinical trial one scale of pain relief is scored backwards relative to another (high on one corresponding to low on the other), with a consequent large negative correlation. But two derived scales of total pain, obtained by multiplying average pain relief on each scale by duration of pain (common to both pain relief measurements) gave an almost zero correlation. This apparent contradiction is explained by the inverse relationship between the pain relief scales and the large differences in duration of pain experienced by the patients. PMID- 1925164 TI - A comparative phase II clinical trials procedure for choosing the best of three treatments. AB - In some clinical trials one can employ adaptive designs advantageously, although in practice such techniques are rarely used, in part due to their inherent complexity. A simple and practicable decision-theoretic approach for the case of three treatments with binary responses is considered, using equal allocation to remaining treatments and, once eliminated, a treatment cannot be re-employed. Having specified the overall number of patients treated within and beyond the comparative stages of the trial, the goal is to maximize the expected total number of those successfully treated. Investigation of the method involves a computer program that can handle arbitrarily large numbers of patients. It is shown empirically that the decision procedure behaves only marginally worse than if the truly superior treatment had been known and had been given to all patients. Implementation of the method uses a minimax approach that removes dependence on prior parameters. Primarily an identification procedure, one advantage of this approach over traditional hypothesis testing methods is the potential to detect small improvements in treatment efficacy. The intended application is to assist in treatment selection during phase II trials, especially with rapid responses and when the disease involved is serious enough that design-motivating ethical considerations become paramount. PMID- 1925165 TI - Using provisional diagnoses in monitoring a clinical trial. AB - In clinical trials there is delay between the occurrence of an event and the recording of that event as an end point in the trial data base. Delays are especially likely if events are reviewed carefully to determine whether diagnostic criteria for end points are satisfied. As a result, the value of a statistic used to evaluate efficacy during a trial may differ from the value of that statistic based on the true end point status of all events which have already occurred. Simulating the process causing delays can be useful in evaluating interim efficacy data by providing a quantitative estimate of the uncertainty in a monitoring statistic. These ideas are illustrated using data from the Lipid Research Clinics Coronary Primary Prevention Trial. PMID- 1925166 TI - Three measures for simultaneously evaluating benefits and risks using categorical data from clinical trials. AB - Randomized clinical trials are typically conducted to compare the efficacy (benefits) and side effects (risks) of two or more treatments. One can use results from such trials to decide on a preferable treatment that reflects one's own evaluation of the benefits and risks. To facilitate the necessary decision making, we propose in this paper three measures for simultaneously assessing benefits and risks. All three measures use weights that reflect the relative importance of the various treatment outcomes to an individual. Two of them carry the flavour of benefit/risk ratios, while the third generalizes Hilden's measure which incorporates patients' preferences. The proposed measures and procedures are illustrated using data from a phase III clinical trial of antihypertensive compounds. PMID- 1925167 TI - Crossover trials, degrees of freedom, the carryover problem and its dual. AB - The problem of carryover in crossover trials has received a great deal of attention in the statistical literature. Carryover is just one form of period by treatment interaction; yet a parallel problem of patient by treatment interaction, which may be regarded as dual to that of carryover, has received little attention. We suggest that the phenomenon of patient by treatment interaction requires a repeated measures approach to the analysis of crossover trials. A simple solution using predefined contrasts is presented and illustrated by example. PMID- 1925168 TI - Detection of outlying data in bioavailability/bioequivalence studies. AB - This paper considers the problem of detecting outlying data in bioavailability/bioequivalence studies. We define outlying subjects as those whose responses in bioavailability to all formulations differ from the rest of the subjects. We also define an outlying observation as the response in bioavailability of a subject to a particular formulation which is grossly different from the average bioavailability of that formulation calculated from all subjects. We propose two test procedures. The first, based on two-sample Hotelling T2, is to detect possible outlying subjects. The second, based on residuals from formulation means, is to identify possible outlying observations within subjects. Both procedures take into account the covariance structure of the responses to formulations, dependence of test statistics, and multiplicity of test procedures. We apply the Monte Carlo or bootstrap simulation to evaluate the sampling distributions of test statistics. An example from a 3-way crossover bioequivalence study illustrates the two procedures. PMID- 1925169 TI - Multivariate probit analysis: a neglected procedure in medical statistics. AB - The multivariate probit model is designed to regress a vector of correlated quantal variables on a mixture of continuous and discrete predictors. Various applications can be found in the biological, economical and psychosociological literature, but the method is not yet widely used in medical applications. We reintroduce this model thereby showing its usefulness in medical problems. Software for this model is, however, not widely available. We have written a PC program to select predictors and estimate parameters in the multivariate probit framework. The performance and characteristics of the program are briefly illustrated. PMID- 1925170 TI - Empirical evaluation of statistical models for counts or rates. AB - We consider methods for selecting the joint specification of the mean and variance functions in statistical models for rates or counts. Based on analyses of diagnosis-specific hospital discharge rates in Michigan, we show that a Poisson model with an extra variance component for the systematic variation is superior to several other probability models with regard to specification of the error structure. Further, the deviance residual appears superior to the Pearson residual. The proper specification of such variation is crucial for many types of analyses, such as identification of outliers and regression analyses designed to explain the systematic component of the variation. PMID- 1925171 TI - Stochastic methods for short term projections of symptomatic HIV disease. AB - We designed and implemented stochastic methods for short term projections of HIV disease at the local level, that accommodate various states or stages of the disease. We gave particular attention to projection of the number of patients with HIV disease who need care, when durations of stay in these various states depend on current methods for treating opportunistic infections. We consider two types of data as input to these projections. One concerns seroprevalence surveys conducted over time and from which we can obtain time series estimates of the numbers of HIV-infected individuals. The other is a reported time series of AIDS cases adjusted for delays in reporting. Several projections, with data from the City of Philadelphia, illustrate this method. In addition, we consider a Monte Carlo method for computing confidence bounds on a projection. PMID- 1925172 TI - Estimation of variance components for censored data with applications to blood pressure variability. AB - Ideally, the basis for estimation of variance components is large random samples selected from a well-defined reference population. Some large biomedical studies, however, consist of a random sample (S) of individuals ascertained at an initial visit, with a selected subsample from S seen on one or more follow-up visits. In this setting, the usual formulae for estimation of variance components are problematic since they do not take into account the censored nature of the data. For this purpose, we consider both maximum likelihood and moments estimation methods that take the censoring into account, and we compare their performance, in terms of bias and mean squared error, with that of the usual variance components estimators that ignore censoring. We find the maximum likelihood estimators somewhat more efficient than method of moments estimators, provided that the assumption of multivariate normality is met; furthermore, these estimators are substantially more efficient than those that ignore the censoring. It is important to record data on all individuals, even those who do not meet screening criteria; one can estimate between- and within-person variance more accurately with use of all available data. The resulting estimates are crucial in calculation of power for the design of future studies. PMID- 1925173 TI - Modelling hearing thresholds in the elderly. AB - This paper concerns a linear mixed-effects repeated measures model in the analysis of a large data set with over 17,000 observations in a longitudinal study of pure-tone hearing perception in the elderly. The repeated measurements are described by fixed and random components in the model. The fixed effects include the age at entry, time of follow-up, a quadratic component in natural logarithm of frequency, a component to allow for participants with hearing impairments, as well as interaction terms between age and frequency and between impairment and frequency. The random factors include a term for subject, a time component and a frequency component. The analysis shows that hearing impaired individuals have similar patterns of hearing loss over time but, on average, have higher hearing thresholds than normal individuals. Estimation of the random effects in the model by restricted maximum likelihood (REML) using the Newton Raphson method made possible the analysis of this large data set with speed and efficiency. PMID- 1925174 TI - A comparison of methods for calculating a stratified kappa. AB - Investigators use the kappa coefficient to measure chance-corrected agreement among observers in the classification of subjects into nominal categories. The marginal probability of classification may depend, however, on one or more confounding variables. We consider assessment of interrater agreement with subjects grouped into strata on the basis of these confounders. We assume overall agreement across strata is constant and consider a stratified index of agreement, or 'stratified kappa', based on weighted summations of the individual kappas. We use three weighting schemes: (1) equal weighting; (2) weighting by the size of the table; and (3) weighting by the inverse of the variance. In a simulation study we compare these methods under differing probability structures and differing sample sizes for the tables. We find weighting by sample size moderately efficient under most conditions. We illustrate the techniques by assessing agreement between surgeons and graders of fundus photographs with respect to retinal characteristics, with stratification by initial severity of the disease. PMID- 1925175 TI - [Recurrent erysipelas]. AB - Erysipelas is clinically defined as a febrile skin infection with a sudden onset of a red indurated expanding plaque with distinct border. A typical erysipelas presents various degrees of cutaneous erythema, oedema and is characterized by less well-defined margins. The responsible agent can be a beta-hemolytic streptococcus (group A), Staphylococcus aureus and other streptococci (group B, C and D). Common predisposing factors are venous insufficiency, lymphatic obstruction and underlying illnesses. Guidelines for the diagnosis and the management of erysipelas are proposed. The episodes of erysipelas ordinarily respond promptly to penicillin or a beta-lactamase resistant antibiotic. Prevention of recurrent erysipelas by means of an antibiotic prophylaxis is discussed. PMID- 1925176 TI - [Prevention and treatment of pressure ulcers]. AB - Pressure is the primary pathogenic factor in the development of ulcers but other major factors are shearing forces, friction and moisture. Significant risk factors are immobility, nutritional status and age-related diseases. Complications of pressure ulcers can be life threatening. The authors wish to stress preventive measures and also recommend a therapeutic approach based on the grade of ulcer present. Prevention is best achieved by identification of high risk patients, alleviation of causative and predisposing factors and early detection of ischemic skin changes. The treatment includes local wound care that eliminates necrotic tissue, decreases bacterial load and provides a physiologic environment allowing the wound to heal, and systemic treatment: adequate nutrition, correction of underlying illnesses and systemic antibiotics (in case of sepsis, cellulitis, osteomyelitis or the prevention of bacterial endocarditis). PMID- 1925177 TI - [An in-vivo culture method for hematopoietic precursor cells: the diffusion chamber technique]. AB - Several studies have demonstrated that hematopoietic cells can be successfully cultured for several weeks in diffusion chambers (DC) implanted both in experimental animals and man. This technique is a useful assay of hematopoietic cell growth and a powerful tool for studying stem cell kinetics in vivo. The evaluation of the effects of humoral factors on hematopoietic cell proliferation and differentiation in this system has led to identification of both stimulators and inhibitors that may be different from the well characterized cytokines. PMID- 1925178 TI - [Pleurisy in ovarian hyperstimulation syndrome]. AB - The syndrome of ovarian hyperstimulation is an exceptional aetiology of pleural effusion. It should be thought of any young women who are under treatment to induce ovulation. The effusions are exudates and not transudates as occurs in Demons-Meigs syndrome. The regression of effusions is usual. PMID- 1925179 TI - [Accidentally discovered interstitial infiltrate]. PMID- 1925180 TI - [Value of the Nd-YAG laser and of endobronchial prostheses in the treatment of tracheo-bronchial obstructions]. PMID- 1925181 TI - [Current aspects of locomotor system pathology: a consultation in specialized podiatry. I: Theoretical bases]. PMID- 1925182 TI - Cycle ergometry and maximal intensity exercise. PMID- 1925183 TI - The Canadian Home Fitness Test. 1991 update. PMID- 1925184 TI - Physiology of exercise in the cold. AB - Recreational and job requirements have increased the incidence in which humans exercise in cold environment. Understanding the physiological responses while exposed to cold entails knowledge of how exercise and cold interact on metabolic, cardiopulmonary, muscle and thermal aspects of human performance. Where possible, distinction are made between responses in cold air and cold water. While there is no consensus for diets most appropriate for working cold exposures, the evidence is strong that adequate amounts of carbohydrate are necessary. Carbohydrate loading appears to be efficacious, as it is for other athletic endeavours. Contrary to conventional wisdom, the combination of exercise and cold exposure does not act synergistically to enhance metabolism of fats. Free fatty acid (FFA) levels are not higher, and may be lower, with exercise in cold air or water when compared to corresponding warmer conditions. Glycerol, a good indicator of lipid mobilisation, is likewise reduced in the cold, suggesting impaired mobilisation from adipose tissue. Catecholamines, which promote lipolysis, are higher during exercise in cold air and water, indicating that the reduced lipid metabolism is not due to a lack of adequate hormonal stimulation. It is proposed that cold induced vasoconstriction of peripheral adipose tissue may account, in part, for the decrease in lipid mobilisation. The respiratory exchange ratio (RER) is often similar for exercise conducted in warm and cold climates, suggesting FFA utilisation is equivalent between warm and cold exposures. The fractional portion of oxygen consumption (VO2) used for FFA combustion may decrease slightly during exercise in the cold. This decrease may be related to a relative decrease in oxygen delivery (i.e. muscle blood flow) or to impaired lipid mobilisation. Venous glucose is not substantially altered during exercise in the cold, but lactate levels are generally higher than with work in milder conditions. The time lag between production of lactate within the muscle and its release into the venous circulation may be increased by cold exposure. Minute ventilation is substantially increased upon initial exposure to cold, and a relative hyperventilation may persist throughout exercise. With prolonged exercise, though, ventilation may return to values comparable to exercise in warmer conditions. Exercise VO2 is generally higher in the cold, but the difference between warm and cold environments becomes less as workload increases. Increases in oxygen uptake may be due to persistence of shivering during exercise, to an increase in muscle tonus in the absence of overshivering, or to nonshivering thermogenesis. Heart rate is often, but not always, lower during exercise in the cold.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1925186 TI - Haemodynamic responses to weightlifting exercise. PMID- 1925185 TI - Kinetic chain exercise in knee rehabilitation. AB - Rehabilitation is recognised as a critical component in the treatment of the anterior cruciate ligament (ACL) injured athlete, and has been the subject of intense research over the past decade. As a result, sound scientific principles have been applied to this realm of sports medicine, and have improved the outcome of both surgical and nonsurgical treatment. Possibly the most intriguing of these principles is the use of the kinetic chain concept in exercise prescription following ACL reconstruction. The hip, knee, and ankle joints when taken together, comprise the lower extremity kinetic chain. Kinetic chain exercises like the squat recruit all 3 links in unison while exercises such as seated quadriceps extensions isolate one link of the chain. Biomechanical assessment with force diagrams reveals that ACL strain is reduced during kinetic chain exercise by virtue of the axial orientation of the applied load and muscular co contraction. Additionally, kinetic chain exercise through recruitment of all hip, knee, and ankle extensors in synchrony takes advantage of specificity of training principles. More importantly, however, it is the only way to reproduce the concurrent shift of 'antagonistic' biarticular muscle groups that occurs during simultaneous hip, knee, and ankle extension. Incoordination of the concurrent shift fostered by exercising each muscle group in isolation may ultimately hamper complete recovery. Modifying present day leg press and isokinetic equipment will allow clinicians to make better use of kinetic chain exercise and allow safe isokinetic testing of the ACL reconstructed knee. Reconstruction of the ACL with a strong well placed graft to restore joint kinematics, followed by scientifically sound rehabilitation to improve dynamic control of tibial translation, will improve the outcome after ACL injury. PMID- 1925187 TI - Fluid replacement and exercise stress. A brief review of studies on fluid replacement and some guidelines for the athlete. AB - Fluid ingestion during exercise has the twin aims of providing a source of carbohydrate fuel to supplement the body's limited stores and of supplying water and electrolytes to replace the losses incurred by sweating. Increasing the carbohydrate content of drinks will increase the amount of fuel which can be supplied, but will tend to decrease the rate at which water can be made available; where provision of water is the first priority, the carbohydrate content of drinks will be low, thus restricting the rate at which substrate is provided. The composition of drinks to be taken will thus be influenced by the relative importance of the need to supply fuel and water, this in turn depends on the intensity and duration of the exercise task, on the ambient temperature and humidity, and on the physiological and biochemical characteristics of the individual athlete. Carbohydrate ingested during exercise appears to be readily available as a fuel for the working muscles, at least when the exercise intensity does not exceed 70 to 75% of maximum oxygen uptake. Carbohydrate-containing solutions appear to be more effective in improving performance than plain water. Water and electrolytes are lost form the body in sweat: although the composition of sweat is rather variable, it is invariably hypotonic with respect to plasma. Sweat rate is determined primarily by the metabolic rate and the environmental temperature and humidity. The sweat rate may exceed the maximum rate of gastric emptying of ingested fluids, and some degree of dehydration is commonly observed. Excessive replacement of sweat losses with plain water or fluids with a low sodium content may result in hyponatraemia. Sodium replacement is essential for postexercise rehydration. The optimum frequency, volume and composition of drinks will vary widely depending on the intensity and duration of the exercise, the environmental conditions and the physiology of the individual. The athlete must determine by trial and error the most suitable regimen. PMID- 1925190 TI - Predictability of sports injuries. What is the epidemiological evidence? PMID- 1925191 TI - [What is your diagnosis? Migrating joint swelling and enthesiopathy in hyperlipoproteinemia type II a]. PMID- 1925189 TI - Rib fractures in athletes. AB - Rib fractures are the most common serious injury of the chest. They occur most commonly in the middle and lower ribs with blunt trauma, and also with direct force to a small area of the chest wall and violent muscle contractions. Diagnosis is generally not difficult. The athlete should have a chest x-ray to confirm the diagnosis. Differential diagnosis includes severe rib contusion, costochondral separations, muscle strains and pneumothorax. If no internal problems exist, treatment consists of ice, NSAIDs, analgesics and a rib belt or tape. Healing should be well on its way before a return to sports. Fractures of the first 4 ribs or the last 2 ribs, multiple fractures and flail segments are less benign than other fractures, and may result in injury to surrounding structures. First rib and floating rib fractures are uniquely athletic fractures; they are avulsion fractures caused by a sudden vigorous contraction in different directions of pull. PMID- 1925192 TI - [Insulin-like growth factor I (IGF I)--a new form of therapy for type II diabetes mellitus?]. PMID- 1925194 TI - [Converting enzyme inhibitors and acute renal insufficiency--precautions to be taken]. AB - Inhibitors of angiotensin-converting enzyme are used commonly nowadays for the treatment of hypertension and cardiac failure. Over the past two years, shortly after the introduction of this type of drug the occurrence of acute renal failure mainly in elderly patients has been reported. The authors have insisted that strict control of renal function and electrolytes are necessary before and after administration of an ACE inhibitor. Particular caution is needed in patients with severe atherosclerotic disease, especially if bilateral (or unilateral in patients with a single kidney) renal arterial stenosis is present or suspected. Considering these limitations ACE inhibitors remain well tolerated and beneficial cardiovascular drugs. PMID- 1925193 TI - [Combined uni- and multicenter double-blind studies in hypertensive patients. Comparison of blood pressure measurements]. AB - In a double-blind study to investigate the antihypertensive effect of a fixed triple combination with 0.05 mg reserpine, 2.5 mg clopamide and 0.4 mg dihydroergocristine in comparison to a fixed double combination with 0.05 mg reserpine and 2.5 mg clopamide, a patient subgroup of 34 patients followed a unicenter (central unit, 'institute') as well as a multicenter (established physicians) study design. The patients visited both investigation units on the day of admission to the study (week 0), after four weeks and after eight weeks of therapy (after the morning intake of the drugs). The paper in hand looks at the results of this subgroup with respect to the conformity of blood pressure values in the two investigative units. The analyses confirm the already published results of the entire study: Both combinations proved to be highly effective antihypertensive drugs. The triple combination showed therapeutical advantages for systolic blood pressure after four weeks, for diastolic pressure after eight weeks of therapy at the 'institute' as well as, although less distinct, in the medical offices. A comparison of the individual values did not show a convincing coherence of the measurements between institute and offices. All investigated possible systematic sources of error (different methods of measurement, days or times of measurement) could be excluded by correlation statistics as a reason for the divergences. The results show the necessity--particularly in multicenter studies--of a careful documentation of all accompanying data (e.g. method or time of measurement) as well as a greatest possible standardization of investigation (e.g. identical measuring apparatus and investigator.) PMID- 1925188 TI - Overtraining in athletes. An update. AB - Overtraining appears to be caused by too much high intensity training and/or too little regeneration (recovery) time often combined with other training and nontraining stressors. There are a multitude of symptoms of overtraining, the expression of which vary depending upon the athlete's physical and physiological makeup, type of exercise undertaken and other factors. The aetiology of overtraining may therefore be different in different people suggesting the need to be aware of a wide variety of parameters as markers of overtraining. At present there is no one single diagnostic test that can define overtraining. The recognition of overtraining requires the identification of stress indicators which do not return to baseline following a period of regeneration. Possible indicators include an imbalance of the neuroendocrine system, suppression of the immune system, indicators of muscle damage, depressed muscle glycogen reserves, deteriorating aerobic, ventilatory and cardiac efficiency, a depressed psychological profile, and poor performance in sport specific tests, e.g. time trials. Screening for changes in parameters indicative of overtraining needs to be a routine component of the training programme and must be incorporated into the programme in such a way that the short term fatigue associated with overload training is not confused with the chronic fatigue characteristic of overtraining. An in-depth knowledge of periodisation of training theory may be necessary to promote optimal performance improvements, prevent overtraining, and develop a system for incorporating a screening system into the training programme. Screening for overtraining and performance improvements must occur at the culmination of regeneration periods. PMID- 1925195 TI - [Swelling of the knee, fatigue]. AB - A 43 year old man was admitted because of fatigue and swelling of the knees. Swelling of both knees, acropachy and turtle-back nails were registered during clinical investigation and laboratory tests showed leucocytosis, increased blood sedimentation rate and alkaline phosphatase. Leucine aminopeptidase was normal. X ray showed symmetric metaphyseal periosteal reactions on femora and tibiae of both sides compatible with hypertrophic osteoarthropathy. A parahilar round tumor measuring 5 x 7 cm infiltrating the right upper lobe was detected on chest x-ray suggestive of lung cancer. Pierre-Marie-Bamberger syndrome was diagnosed (hypertrophic osteoarthropathy associated with cancer of the lung). Under radiotherapy to the tumor the osteoarthropathy subsided and alkaline phosphatase returned to normal. PMID- 1925196 TI - [A case from practice (223). Diabetic ketoacidosis]. PMID- 1925197 TI - [What is your diagnosis?]. PMID- 1925198 TI - [Visitor returning from the tropics 1991]. PMID- 1925199 TI - [Cardiovascular risk factors of visitors to a mass-screening booth]. AB - The attitude towards mass screening of serum cholesterol is controversial. In order to characterize the volunteers of such screenings and to test the representativity of its findings, we compared the data of 1686 adult health screening participants collected during a trade fair in the city of Basel, Switzerland, with the results of two population-based studies, the Basel City Risk Factor Survey and the MONICA Project in Western Switzerland. Among those screened, there was an over-representation of women and older persons. The age specific medians of blood cholesterol and proportions of hypercholesterolemic persons were consistently higher in female screenees--and marginally so in males- than in the reference populations, whereas higher proportions of persons with ideal cholesterol level in those screened were also observed, especially in younger males. Higher systolic blood pressure, lower relative body weight and less regular smoking were found consistently among the screenees. This cross sectional study shows that the participants of such mass screening actions are a selective group of older, more frequently female health-conscious persons with a specific risk-factor pattern. Mass screenings of self-selected volunteers can, therefore, not be used for a reliable prediction of risk-factor distributions in the general population. Moreover, suggested further steps for those screenees with both health-conscious behavior and elevated biological risk-factor levels, such as second measurement, medical consultation and counselling, cannot be assured in the setting of a trade fair. The objectives and intentions of such mass screening activities should be reconsidered and discussed. PMID- 1925200 TI - [A case from practice (224). Acute exogenous reaction type (delirium) following administration of Tigason]. PMID- 1925202 TI - [Advances in clinical epileptology]. PMID- 1925201 TI - [What is your diagnosis? Furunculoid myiasis]. PMID- 1925203 TI - [Variability in seizure phenomenology in the same epileptic patient]. AB - There are many different causes for an alternate outbreak of different seizure manifestations in the same patient. According to Herpin's 'law of identity', this is more a question of differing degrees of intensity of the same seizure type. Subsequently, minor or partial seizures are to be interpreted as rudimentary forms of 'major' seizures. This may be true for some, but not for all cases. It would be daring to maintain that a typical absence is a rudimentary form of a 'grand mal' seizure. Their mutual pathogenetic relations are unknown. A series of other cases would likewise go beyond the scope of Herpin's law. A patient can show, even during a cerebral condition of the same etiology, several different localized epileptogenic foci which 'flame up' alternately and initiate different types of seizures. Progressive cerebral illnesses can lead to a change in the original seizure symptoms and can also trigger off additional seizure forms. This can occasionally occur during medication. Finally, it is necessary to consider the possibility of an alternate outbreak of epileptic and nonepileptic seizures in the same patient. PMID- 1925204 TI - [Variability of phenomenology of epileptic crises in the newborn infant]. AB - Epileptic seizures are more common in the newborn period than at any other time of life. If ictal behaviors accompany ictal EEG discharges, there is no particular problem. However, the most pressing controversy is whether neonatal seizures should be diagnosed on the basis of behavioral or EEG criteria. The proportion of seizures that are subclinical is much higher during the neonatal period than at any other time of life. Therefore the frequent occurrence in an intensive care unit of both subclinical seizures and suspicious stereotyped behaviors renders EEG of critical importance in the diagnosis of neonatal seizures. The authors discuss the large field of clinical and EEG phenomenology of neonatal seizures after twenty years of experience with EEG in neonatology. PMID- 1925205 TI - [Variability of epileptic seizure phenomenology in infants and children]. AB - It is well known that some patients may have two or more different types of seizures. Partial epilepsies and more than 15 different epileptic syndromes (e.g. West or Lennox-Gastaut syndrome or epilepsies with absences) can lead to the intraindividual manifestation of two or more seizure types. Among 728 children with epilepsy seen at the outpatient department 9.1% had two different types of seizures and 1.5% had more than two types of seizures. The most common association observed was between tonic-clonic seizures and absences. The most frequently observed epileptic syndromes were in decreasing order: multifocal epilepsies, epilepsies with absences, Lennox-Gastaut syndrome and West syndrome. The association of two or more different seizure types in the same patient seems to be a negative prognostic factor. PMID- 1925206 TI - [Variability of seizure phenomenology in the light of stereo-EEG studies]. AB - The demonstration of a largely stable electroclinical semiology in the early phase of seizures is a main prerequisite for successful causative surgery of epilepsy. A few experiences with analysis of similarities during seizures are presented and discussed regarding their fundamental pathogenetic but also practical clinical significance. The primary data stem from candidates for selective surgery of the temporal lobe, mainly afflicted by psychomotor seizures. These seizures were recorded either by invasive stereoelectroencephalography or by semi-invasive foramen ovale electrodes. PMID- 1925207 TI - [Long-term follow-up in patients with Lennox-Gastaut syndrome. Epileptological aspects, psychomotor development and social adaptation]. AB - In 1989/90 a follow-up was made possible on 72 of 78 patients who have been treated for the supposed or confirmed diagnosis of a Lennox-Gastaut-Syndrome at the university children hospital of Berne between 1964 and 1978. Nine patients were excluded of this study because the diagnosis was proved wrong retrospectively, leaving 63 cases. Of these, eleven patients (17.5%) have died. The remaining 52 (82.5%) were evaluated regarding their epilepsy, psychomotor development and social adaptation. The follow-up was good for 14.3%, intermediate for 23.8% and poor for 44.4%. Bad prognostic factors were found to be: first manifestation of epilepsy during the first year of life, occurrence of infantile spasms or hypsarrhythmia in the EEG and pathological neurological signs at the beginning of the disease. In the course of illness a change of seizure phenomenology was observed. The infantile spasms were seen only during the first three years of epilepsy. After the second year of disease psychomotor seizures became more and more frequent. Atypical absences, already seen at the beginning, were the most frequent form of seizure from the third year of epilepsy until the end of our observations. During the course of disease the frequency of generalized tonic and tonic-clonic seizures decreased little. PMID- 1925208 TI - [Prognostic value of the EEG prior to the start and the discontinuation of anticonvulsive therapy]. AB - Opinions are divided about the prognostic value of the EEG in the course of epilepsy. We thus prospectively examined 275 children with epilepsy; in particular, we analyzed the prognostic role of the EEG. Out of these 275 children 209 (76%) have been free from attacks for more than one year. In 107 children the anticonvulsive therapy was discontinued, leading to a relapse rate of 27%. According to our results, only the focal EEG changes, up to interruption of the anticonvulsive therapy, show a statistical significance in the course of epilepsy. On the other hand, a normal EEG before or normalization of the EEG after commencement of therapy and also the absence of any epileptic activity (focal or generalized), are likely to be favourable. However, we could not find a statistically significant difference. PMID- 1925209 TI - [What is your diagnosis? Garre's sclerosing osteomyelitis]. PMID- 1925210 TI - [Sudden hearing loss]. PMID- 1925211 TI - [Aspects of cerebral circulation in children]. AB - Investigation of cerebral circulation represents an essential diagnostic adjunct to pediatric neurology. Doppler-sonography is presented as one of the diverse techniques to examine cerebral hemodynamics. The human cerebral circulation is controlled by autoregulatory mechanisms. Factors such as hematocrit, pulse, orthostasis and physical activity modulate the cerebral blood supply. The demand for blood depends essentially on arterial pCO2 but also on behavioural situations such as mental activity, effect of sensory stimuli or sleep. Bioelectric activity and perfusion of the central nervous system are closely linked. The cerebral perfusion in infants is characterized by a rapid increase in flow over the first couple of years to values exceeding those of adults. Disturbances of the cerebral perfusion are found in a variety of pediatric diseases. The patterns of perinatal brain damage depend on the maturity of the newborn. They are mainly sequels of impaired cerebral perfusion. In prematures periventricular leukomalacia and intracerebral hemorrhage are frequent whereas in infants at term cerebral edema and infarcts are more common. Acute hemiplegia in childhood can be of thromboembolic or vascular origin, however of etiologies different from those in adulthood. Prevention is the best treatment for disturbances of cerebral perfusion in childhood. Continuous monitoring techniques and pharmacotherapy need further clinical investigation. PMID- 1925212 TI - [Clinical aspects and epidemiology of cryptosporidiosis in immunocompetent children]. AB - A prospective case-control study was performed in urban and periurban areas of Basel to investigate the epidemiology of Cryptosporidium sp., an intestinal coccidian parasite. 455 children with diarrhoea, who attended paediatric and general practices, participated in the study. Oocysts of the parasite were detected in stool specimens of 21 (4.6%) patients using auramine-fluorescence and modified Ziehl-Neelson staining. Another ten infected people were found during separate investigations of outbreaks in a Kindergarten and in two families. Serial stool stains were performed to determine the period of oocyst shedding. The median duration of diarrhoea was six days and ranged from 1 to 25 days. In contrast, shedding of oocysts of Cryptosporidium sp. lasted for 12.5 days and was significantly longer than the period of diarrhoea (p = 0.02). Compared with control patients suffering from diarrhoea of other origin, respiratory symptoms were significantly (p = 0.02) more frequent in children with cryptosporidiosis (42% vs 13%). In comparison with healthy controls, prior contact with a person suffering from diarrhoea and travel to a Mediterranean country were the most important risk factors for cryptosporidiosis. An illustrative case is described in detail. It is concluded that cryptosporidial infection of the respiratory tract may also occur in immunocompetent children. The possibility of a long period of oocyst shedding is important for the planning of hygiene measures both in individuals and public health. PMID- 1925213 TI - [Diagnostic accuracy in bacterial infections in an emergency ward: results of a retrospective study]. AB - Accuracy of the initial diagnosis and the appropriate choice of antibiotics were evaluated in a group of patients with presumed bacterial infections admitted to the medical ward after initial examination at the emergency ward. A bacterial infection was initially suspected and treated with antibiotics in 88 (33%) of 265 patients admitted consecutively. An inaccurate diagnosis of bacterial infection was made in 2.6% of all patients and in 8% of the patients treated with antibiotics. In one patient (0.4%) the presence of a bacterial infection was overlooked. Penicillins, co-trimoxazole, erythromycin and aminoglycosides represented 93% of the antibiotics chosen. 28% of all empiric antibiotic regimens had to be modified due to the result of sensitivity testing, side effects or clinical failure. PMID- 1925215 TI - [A case from practice (225). Tropical sprue. Reflux esophagitis II]. PMID- 1925214 TI - [Bacterial sensitivity to chemotherapeutic agents (Zurich, 1990)]. AB - This paper describes the incidence of susceptibility of gram-negative and positive bacteria towards antibacterial agents. The data are based on all susceptibility tests performed at the Department of medical microbiology of the University of Zurich. The evaluation of the results from 1975 to 1990 shows that susceptibilities against the antimicrobial agents tested have not changed markedly in this period. These tables may be a help for the physician in his decision for a "calculated chemotherapy" of bacterial infections. PMID- 1925216 TI - [What is your roentgen diagnosis? Acute emphysematous cholecystitis]. PMID- 1925217 TI - [The face of depression]. AB - While describing mimic and pantomimic aspects in depressive patients, the author points out how these features can often be found clearly reproduced in the paintings of artists. Then paintings of a depressive and suicidal female patient are discussed and compared with paintings of a talented student-nurse from our institution expressing her experiences with depressive patients. Also some examples of literary depiction of experienced depression are discussed. Finally the question is posed whether suicidal individuals can be freed from their ideas and impulses by pictures expressing suicidal ideas. PMID- 1925218 TI - [Mood and state of mind]. AB - Man's basic mood is of far greater significance than commonly assumed. It is communicated to his fellow man from afar, by his facial expression, and thus can cast a long shadow upon human relations. As this is an unconscious phenomenon, the pre-existing mood is reconfirmed by each encounter--a self fulfilling prophesy. The realization that a pre-existing mood determines our experience more than the reality of the experience itself is nothing new. It is pointed out in both ancient Greek and far Eastern philosophy, in the Bible, and in modern psychology. Every human being has the ability to influence his mood through self own awareness. If he fails to do this, his features become frozen and unalterable, like the Person, the mask of the classic Greek theatre. While alterations of mood are considered normal phenomena, depression must be seen as a manifestation of pathological affect, usually accompanied by somatic symptoms. Depressions have been known and described since the dawn of mankind. 15 bis 25% of all depressives commit suicide. They are treated preferably by a combination of pharmaco- and psychotherapy. In the realm of the latter, Beck's Cognitive Therapy has proven to be especially efficacious. As this is a common and dangerous illness, it is very important for every physician to be familiar with it. Not only to save lives by instituting adequate treatment, but to open one's heart and to empathize with the patient, to see in him a brother rather than merely an object of scientific exploration. PMID- 1925219 TI - [Psychosomatics and depression]. AB - In our opinion psychosomatics are a consideration that ought to be at the basis of all medical reflection and action. Illness declares itself in the various interhuman relations (incl. physician-patient-relation); every category of syndromes (for instance the "psychosomatic-one") can be understood as a certain relation-modus. A multidimensional way of contemplation has to be gone even if the actual situation of the illness and the point of view of the physician put either the somatic-biological, or the psychic or the social aspect in evidence. In this case the visible symptom leads to detect the intra-psychic and interhuman problems and conflicts. If the physician and the patient stay remained on the apparent symptom all diagnostical or therapeutical actions are nothing more than Don Quichotism without success, a disappointing battle against the wind-mill sails of symptoms. PMID- 1925220 TI - [Pharmacotherapy of depression]. AB - Four cardinal rules for pharmacotherapy of depression are discussed: 1. Severity of depression is the main criterion for the decision to treat by drugs. 2. The profile of side effects of antidepressants furnishes the arguments for drug selection. 3. Sufficiently high doses are the main prerequisite for rapid and strong response. 4. The sooner the treatment with an antidepressant is initiated, the earlier an effect of treatment can be expected. PMID- 1925221 TI - [The spiritual dimension of depression]. AB - When an individual suffers from living, when he questions the meaning of existence, when he is obsessed by feelings of worthlessness, he becomes a sufferer. Perhaps invisible for a long time and initially covered by somatic events, suffering from living finally manifests itself with its real face--not simply illness but being ill. This exceeds biologic organic processes, and a sheer medical approach to depression is no longer adequate. Other explanations will be needed. What discriminates a spiritual view e.g. from biomedical approaches to understand depression is the attitude taken towards the existence of a spiritual reality and towards the forces from deep within (inner resources). This means that spiritual and religious impulses and aspirations are deemed equally fundamental as other manifestations of life. Using a real case history, the path of suffering and recovery of a woman is presented. PMID- 1925222 TI - [Goethe's struggle with depression]. AB - Goethe was subjected during his whole life to extraordinary psychic threats and polar tensions often to the limits of destruction. For long periods of life he travelled in the mist of depression. By steady patience, constant endurance, disciplined diligence, self-control and self-denial as well as restless activity inward and outward he resisted serious depressive threats and did not get paralyzed. He rather faced his spiritual sorrow creatively and forced it into curative poetry. While being completely uncommon, his wise but old-fashioned recipes on ways to master one's depression are a psychotherapeutic bequest and remain valuable up to our days as complement to our modern concepts. PMID- 1925223 TI - [Dementia: classification, diagnosis--in search of treatable causes]. AB - There are so many possible etiologies of dementia that its evaluation must be well directed. The neuropsychological examination permits the diagnosis of dementia and allows for a classification of a dementia as 'cortical' dementia, i.e. with aphasic, apraxic or agnosic disturbances, or 'subcortical' dementia, which is mainly characterized by psychomotor retardation. Virtually all treatable dementias present as 'subcortical' dementia. The search for a cause of a dementia includes the clinical setup and a number of additional examinations, which may reveal causes that were not suspected on clinical grounds. In this paper we propose a classification of dementias based on the distinctions 'cortical/subcortical dementia' and 'somatic neurological examination normal/abnormal'. Furthermore, we suggest an array of additional examinations which in our view should be performed in any case of dementia. PMID- 1925224 TI - [Neurological examination of the elderly. Principle modifications and most frequent abnormalities]. AB - This article will review age-related changes in the neurological examination. The involutional process is a diffuse one, affecting all levels of the neuraxis simultaneously. Most of the numerous little manifestations distinguishing them so sharply from the youthful are really features of the neurology of the elderly. Some signs are characteristic: attitude of general flexion, general poverty of movement, gait, minor extrapyramidal signs, primitive reflexes. However, these features may also be caused by neurological diseases common in the elderly, such as dementia or cervical myelopathy, which is very common after 75 years. PMID- 1925226 TI - [Physical therapy aspects of treatment following total hip prosthesis]. AB - Our physiotherapy program after total hip arthroplasty is presented, and certain modifications in relation to cemented or cementless implantations are discussed. Three different stages must be considered: preoperative instructions of the patient, mobilization of the patient and his joints, water gymnastics to enable the patient to obtain total independence. During the first three months only partial weight should be put on the operated leg. In comparison to the cemented system, the biomechanical properties of the cementless prosthesis permit only a careful and delayed mobilization and charge of the operated leg, as long as a secondary stability of the implant has not been reached. In more complicated cases it is of importance that the whole planning of postoperative physiotherapy should be discussed individually and in detail with the surgeon concerned. PMID- 1925225 TI - [Regression of coronary atherosclerosis: possible--and clinically relevant?]. AB - Several recent clinical trials have shown that in male patients with stable coronary heart disease, progression of atherosclerosis can be delayed even in short time. The interventions to bring about less progression and even a regression of coronary artery lesions mainly consisted in lowering high lipid levels, either with drugs, partial ileal bypass surgery or comprehensive lifestyle changes. The results of trials using calcium antagonists were less consistent and failed to show clear-cut slowing or prevention of progression. Some questions, however, arise and are discussed: i.e. the shortcomings of quantitative angiography to assess the extent of atherosclerotic lesions and the clinical importance of the observed changes in luminal diameter, which tended to be small. Despite these intriguing issues, the reported studies provided the additional information that the angiographically demonstrated benefits were paralleled by a reduction of clinical vascular events and an improvement of the short-term clinical outcome. PMID- 1925227 TI - [Septic syndrome with a pulmonary focus]. AB - After acute pharyngitis a 21 year old patient developed signs of severe bacteremia with a well demarcated infiltrate in the left lung. The typical course and a prompt response to antibiotic therapy with Imipenem (Tienam) led to the diagnosis of Lemierre's syndrome (post-anginal sepsis)--in spite of negative blood cultures. The patient recovered quickly, a chest radiogram after two weeks showing but pleural scarring and restitution ad integrum after four weeks. PMID- 1925229 TI - [What is your diagnosis? Destructive spondylopathy in chondrocalcinosis (histologically confirmed)]. PMID- 1925228 TI - [What is your roentgen diagnosis? pneumoperitoneum following intestinal perforation]. PMID- 1925230 TI - [Long-term fever in a patient born in India]. PMID- 1925231 TI - [Bladder carcinoma following bladder tuberculosis]. AB - Two females developed squamous cell carcinoma of the urinary bladder several years after tuberculosis of this organ. These observations are compared with similar reports. It is striking that in this situation squamous cell carcinomas occur almost exclusively as has become known from carcinomas of the bladder developing after other chronic infections. PMID- 1925232 TI - [Nicotine weaning in clinical practice]. AB - A few facts about the smoking problem, strategies and possibilities of nicotine withdrawal in practice and thoughts on prevention of recurrence of smoking are reviewed. This presentation is intended as support to the antismoking campaign of the Swiss Health Office and the Federation of Swiss Physicians. PMID- 1925233 TI - [Occupational asthma]. AB - The recognition of bronchial asthma as occupational disease is essentially a matter of legislation and not of medical definitions. Swiss law accepts an occupational nature of asthma when its causes derive to more than 50% from the work place. Causes are extremely diverse, whereby in Europe flour (bakers) and isocyanates (spray lacquers) dominate. Together, these causative agents contribute close to 50% of all cases of occupational asthma. The clinical picture is that of classic bronchial asthma. Peculiarities are seen only regarding the temporal dependence between exposition and beginning of airway obstruction. Regarding diagnosis of occupational asthma the following questions should be answered. 1. Is the dyspnea described by the patient real bronchial asthma? 2. Is there a documented temporal connection between exposition and complaints? 3. Is there a causative agent at the work place? Peak-flow measurements are particularly useful for documentation of connection of symptoms with occupation. They demand, however, a certain degree of cooperation by the patient. The prime therapeutic measure is avoidance of further contacts with the responsible agent. The Swiss health authorities (SUVA) have the power to issue decisions of unsuitability for certain workplaces or exposures. Such a measure is however severe and requires therefore a careful diagnosis and an evaluation of risk and benefit for the patient. PMID- 1925234 TI - [Hypo- and hyperventilation: consequences for acid-base balance]. AB - Deviations of the alveolar ventilation rate from normality induce respiratory acid-base disturbances. Alveolar hyperventilation leads to hypocapnia and thus respiratory alkalosis whereas alveolar hypoventilation induces hypercapnia leading to respiratory acidosis. The changes in CO2 induce compensatory alterations of renal bicarbonate transport: Hypercapnia stimulates renal reabsorption of bicarbonate whereas hypocapnia enhances urinary bicarbonates. The plasma bicarbonate concentration rises in response to hypercapnia and falls following hypocapnia. Renal regulation of plasma bicarbonate results in a characteristic dependence on systemic PCO2 permitting the formation of diagnostic criteria for respiratory imbalance of acid-base homeostasis. In chronic respiratory acidosis plasma bicarbonate should rise by 0.35 mmol/l per mmHg increase in PCO2. In chronic respiratory alkalosis, on the other hand, plasma bicarbonate should fall by 0.4 mmol/l for every mmHg decrease in PCO2. If the measured bicarbonate values do not fall into this expected range, acute respiratory or mixed (respiratory and metabolic) acid-base disturbances should be suspected. The clinical significance and application of these diagnostic criteria are illustrated by examples. PMID- 1925235 TI - [Nutrition in kidney diseases]. AB - Three dietary measures are useful for chronic progressive renal failure. In a hypertensive patient, salt restriction is a prerequisite for antihypertensive therapy. Protein restriction to 0.6 g/kg of body weight per day can slow down progression of renal disease with the exception of polycystic disease of the adult type. Ketosteril can be given for prevention of essential amino acid deficiency. A normalization of serum phosphorus is essential for slowing progression of disease as well as bone metabolism. Therefore, a diet reduced in phosphates, supported by phosphate binders is prescribed. PMID- 1925236 TI - [Pickwick syndrome. A case example of an obesity-hypoventilation syndrome, combined with obstructive sleep apnea]. AB - Nocturnal intrinsic disorders of sleep are much more common than hitherto assumed. In middle-aged men, a prevalence of 0.3 to 3% of severe obstructive sleep apnea syndromes necessitating treatment is expected. The international classification of sleep disorders (ICSD 1990) contains the definitions and descriptions of the different entities. A patient with combined obstructive sleep apnea and a hypoventilation syndrome due to obesity serves to illustrate problems with diagnosis and particularly treatment of this respiratory disorder during sleep. The most frequent sleep disorders are briefly presented and placed in the context of other concomitant somatic diseases. Because of the possible serious course of nocturnal hypoxemias, the conclusion is justified that a timely and accurate diagnosis is essential for the patient. Transcutaneous oximetry during the night is sufficient as screening procedure. It can be applied to outpatients. In depth, evaluation should be carried out at a specialized center with polysomnography. PMID- 1925237 TI - [Pain syndromes of the shoulder]. PMID- 1925238 TI - [Autotransfusion procedures in a district hospital]. PMID- 1925239 TI - [Celiac disease in adults]. PMID- 1925240 TI - [Peripheral facial paralysis and Lyme borreliosis]. PMID- 1925242 TI - [Low T3 and low T3-T4 syndrome]. PMID- 1925241 TI - [Indwelling catheter and urinary infection]. PMID- 1925244 TI - [Oral antidiabetic agents: what are the choices?]. PMID- 1925243 TI - [Low-level rhesus alloimmunization and other alloimmunizations in pregnancy]. PMID- 1925245 TI - [Psychiatric consultation and emergencies: from model to practice]. PMID- 1925246 TI - [Tumor markers in oncological practice]. PMID- 1925247 TI - [12 theses on drug abuse]. PMID- 1925248 TI - [April flies]. PMID- 1925249 TI - Immunotherapy of cancer with lymphokines and lymphokine-activated killer cells. AB - Our expanding knowledge of the immune system has provided a basis of rationality for immunotherapy. Some non-specific immunotherapy has achieved the status of standard treatment: interferon in hairy cell leukemia and chronic myelogenous leukemia, BCG in bladder cancer, and levamisole in colon cancer adjuvant therapy. Tumor infiltrating lymphocytes, moreover, offer a level of specificity heretofore unknown. Combined with the newly available synthetic cytokines that regulate the normal immune system there is the potential for a major breakthrough in biotherapeutics. Problems remain. We have yet to identify tumor antigens with the precision necessary for effective immunotherapy. Indeed, we have no assurance that tumors will regularly synthesize new antigens. In the broad spectrum of immune deficiency syndromes, we have yet to see an increase in the common epithelial tumors that account for the great bulk of human cancer. This suggests that we still have a great deal more to learn. PMID- 1925250 TI - Experimental trials of immunotherapy for malignant melanoma. AB - Conventional treatment for metastatic melanoma consists of surgical resection, chemotherapy, and radiation therapy. New approaches toward treatment of this disease include the development of passive and active immunotherapeutic regimens. Malignant melanoma is particularly amendable to immunotherapy since the tumor is relatively immunogenic, expressing unique cell surface protein and lipid antigens. Clinical trials investigating the benefit of active specific immunotherapy documented increased survival of invasive Stage 1 and metastatic Stage 2 melanoma patients following immunization with tumor cell vaccines and BCG. Additional trials showed that the development of specific antibodies after immunization of Stage 2 patients with a viral oncolysate was correlated with an increased survival compared to matched controls given only BCG. Passive immunotherapy approaches using either lymphokine-activated killer (LAK) cells or tumor-infiltrating lymphocytes (TIL) administered with interleukin 2 have also resulted in regression of disease with complete or partial remissions occurring in 25% of the patients. Additional studies have focused on the generation of specific cytotoxic T lymphocytes by stimulation with autologous tumor in vivo. Future trials will evaluate the therapeutic efficacy of these specific cytologic T lymphocytes relative to LAK and TIL. PMID- 1925251 TI - Active specific immunotherapy and immunochemotherapy in the treatment of lung and colon cancer. AB - In this seminar, we describe 1) the immunogen TAA used for lung cancer immunotherapy and the immunogen TAA used for colon cancer immunotherapy, 2) the methods used in the administration of these immunogens in clinical trials of specific active TAA immunotherapy, 3) the results of clinical trials of specific active immunotherapy for lung cancer and for colon cancer patients, 4) the results of immune response monitoring evaluations, and what they indicate, and 5) the way in which certain drugs, selected for their action in the immune system, may be synergistic with specific active TAA immunotherapy, in combination therapy, especially for resected patients of later stages. PMID- 1925253 TI - Immunotherapy for malignant melanoma: a review and update. AB - Several different approaches to the application of specific active immunotherapy for the adjuvant therapy of melanoma have developed independently. Specific active immunotherapy refers to autologous or allogenic inoculation or transplantation of tumor cells or cell products into patients with cancer. Several different types of tumor vaccines have been studied and have been combined with different immunotherapeutic modalities. This report will include a review of several of those different techniques and will also review the observed 5-year survival rates for a melanoma tumor homogenate (concentrated) vaccine, developed by L.J. Humphrey and colleagues. PMID- 1925252 TI - Immunotherapy of breast cancer: a review of the development of cell-specific therapy. AB - A brief history of immunotherapy for breast cancer is presented, with emphasis on how theories developed as the field of immunology became more sophisticated. Non specific therapies, such as Bacillus Calmette-Guerin, levamisole, interferon, interleukin, and others are reviewed. A form of cell-specific immunotherapy is then presented, and some current results are summarized. Problems and proposals for the future development of immunotherapy for breast cancer are then presented. PMID- 1925254 TI - Immunotherapy of renal cell cancer. AB - Immunotherapy of metastatic renal adenocarcinoma (RCC) is currently an alternative to cytotoxic chemotherapy. Bacillus Calmette-Guerin has been associated with a 22% response rate in small series, but no large-scale clinical trials have been completed. Transfer factor, in combination with other immunotherapeutic and chemotherapeutic compounds, has a reported 13% incidence of response. Tumor vaccines have caused clinical response in only 5% of patients while monoclonal antibodies have produced partial remission in one of nine patients. Immune RNA has been associated with a 14% overall incidence of response. Tumor necrosis factor has not as yet been studied in any large-scale clinical investigations but preliminary studies are not promising. Leukocyte derived and recombinant interferons alone have produced responses in 10-20% of patients with tolerable toxicity. Combinations of interferons or with cytotoxic chemotherapy have produced slightly improved responses with short duration and substantial toxicity. Adoptive immunotherapy using Interleukin-2 alone, or with IL-2 plus lymphocyte-activated killer cells, or tumor infiltrating lymphocytes or interferons have produced clinical responses in 10-30% of patients treated. Combinations of specific forms of immune therapy may hold promise for better rates of clinical response in the future. PMID- 1925255 TI - Immune responsiveness of patients with malignant melanoma and carcinoma of the breast. AB - Lymphocyte blastogenesis (LB) with PHA, CON-A, PWM, VII (homologous tumor extract) plus T/B ratio for pre-IT, post-IT (2 months), and 3, 6, 9, 12, 18, and 24 months prior to each VII booster are reported. Pre-IT and post-IT LB-PHA were similar for Stage I (ST I) or Stage II (ST II) breast cancer (BC) patients who expired or survived. The pre-booster results were similar except that prior to death, stimulation with PHA decreased. Melanoma (MM) patients LB-PHA pre-IT showed less stimulation for ST I patients than for ST II patients (survivors and expired). LB-CON-A and LB-PWM showed similar results with slight variations. When compared to survivors, LB-VII for BC patients who expired showed no stimulation. MM patients showed different results in LB-VII. T/B ratios for BC patients during the first 3 months showed 72% normal (N), 14% below N, and 14% above N for survivors and 40% normal (N), 60% below N, and 0 above N for expired. MM T/B ratio were not remarkable. LB anamnestic response to immune stimulation evaluated in 16 of the 62 BC and 10 of 81 MM patients showed increased peak levels over trough for survivors and a decrease for expired. The significance of data as in vitro correlates of clinical response is discussed. PMID- 1925256 TI - Role of immunotherapy in the treatment of bladder and renal cell carcinoma. AB - Much remains to be learned about the immune response in human neoplasia both in a phenomenological sense and in its therapeutic possibilities. Recruitment of immune response mechanisms in the defense against cancer development and in the cure of advanced disease, though theoretically sound, remains to be proven in demonstration of both its phenomenological and clinical efficacy. The most important steps in this regard will require an analysis of those mechanisms that may truly be active in human cancer. Their enhancement and effective delivery to various tumor sites, then reliable monitoring, and proof of their efficacy will be necessary to accomplish before any conclusive statement can be made as to the usefulness of immunotherapy in the treatment of genitourinary neoplasia and of human cancer in general. PMID- 1925257 TI - [Significance of subjective symptoms in the diagnosis of hyperviscosity syndrome]. AB - A questionnaire including 9 main signs: headache, vertigo, vision and hearing derangement, fatigue, hemorrhage, somnolescence, loss of appetite has been elaborated and introduced into the clinical practice. It was revealed that patients with Sjogren's syndrome had an elevated viscosity of the serum in 30% of the cases. These patients complained of headache and vision derangement more often than those with normal indices, though in the first group it did not reach critical values corresponding to an extended clinical picture of the hyperviscous syndrome. The mentioned questionnaire can be used for early diagnosis of the rheological properties of the blood. PMID- 1925258 TI - [Functional state of the endocrine glands and the immune system in patients with juvenile rheumatoid arthritis]. AB - A total of 35 patients aged from 5 to 12 years old suffering from the articular, visceral or polyarticular form of juvenile rheumatoid arthritis (JRA) were examined. The functional state of the endocrine glands were determined by means of appliances intended for radioimmunological study. To characterize the immune status of patients the conventional methods of investigation were used. The analysis of the material showed that all the patients with JRA had disorders in the system: hypophysis--adrenal cortex, the system: hypophysis-thyroid gland and pancreas suffer to the least degree. Disorders were mostly marked in patients with the articular- visceral form of JRA and those with a protracted course of the disease (two or more years). Relationship between hormonal and immune parameters was revealed. PMID- 1925259 TI - [Changes in the hepatobiliary system in juvenile rheumatoid arthritis]. AB - The authors submit the results of echographic investigation of 42 children aged from 4 to 15 years old with juvenile rheumatoid arthritis (JRA). All the patients were distributed into three groups. Signs of affection of the hepatobiliary system were revealed in 60% of the patients, predominantly with the articular form of the disease and in 78.5% of the children with the articular -visceral form. The most grave changes were noted in the group of patients with JRA complicated by secondary amyloidosis (100%). The data obtained are compared with the clinico-laboratory indices, the form of the disease, peculiarity of therapy as a result of which a relationship between the mentioned signs and the character of JRA lesions is established. A high informativeness of the echographic method especially in the diagnosis of secondary amylosis is confirmed. PMID- 1925260 TI - [Approach to evaluation of the indicators of Yersinia infections in reactive and rheumatoid arthritis]. AB - A total of 140 patients with reactive arthritis due to Yersinia infection were under observation for 2-10 years. A group of 104 patients with erosive rheumatoid arthritis served as control for analysis of the results of bacteriological and serological studies. The bacteriological analysis of the feces, urine, smears of the feces and blood were made repeatedly. As established the articular syndrome in reactive arthrosis has its specific features depending on the nature of the pathological process: primary, recurrent and chronic. Patients with primary reactive arthritis exhibited recovery without residual phenomena and relapses in 35.8% of the cases; in 86% the disease relapsed; in 36% it was chronic, persisting for a number of years as a non-erosive seronegative arthritis; in 25.3% arthralgia persisted; in 6.2% the clinical picture of secondary osteoarthrosis developed; in 17.3% the disease changed into spondyloarthritis and in 1.2% of the cases it changed into RA. Since in reactive arthritis Yersinia infection was confirmed in 48.5% of the cases and in RA in 14-21%, laboratory diagnosis cannot serve as an absolute criterion for reactive arthritis. It is necessary to take into consideration the anamnesis and the peculiarities of the clinical picture and the course of the articular syndrome. PMID- 1925261 TI - [Effect of non-steroidal anti-inflammatory agents on kidney function in patients with rheumatoid arthritis]. PMID- 1925262 TI - [Ankylosing spondyloarthritis in children and adolescents]. PMID- 1925264 TI - [Characteristics of the onset of systemic lupus erythematosus in an adolescent with the symptoms of acute diffuse peritonitis]. PMID- 1925263 TI - [Characteristics of using non-steroidal anti-inflammatory drugs in patients with arterial hypertension]. PMID- 1925265 TI - [Clinical observation of rheumatoid pancarditis]. PMID- 1925266 TI - [Problems of classification and the criteria of diagnosis of chronic arthritis in children]. PMID- 1925267 TI - [A method of administration of drugs into the small joints of the hand and foot]. PMID- 1925268 TI - [Changes in beta-glucuronidase activity in the blood cells and blood serum of patients with rheumatism in relation to clinical manifestations of the disease]. AB - The authors examined 22 patients with rheumatic fever in whose cells (neutrophils, mononuclear cells, thrombocytes) and in the blood serum they noted the activity of lysosomal enzyme of beta-glucuronidase (BGU) and the concentration of protein in the cells of the peripheral blood. The activity of the enzyme and concentration of protein in neutrophils of mononuclear cells was found to be decreased. Differences in determining the activity of BGU in the blood serum in relation to the clinical manifestations of the disease were also established. A significant rise in the activity of BGU in the blood serum as compared to the norm was observed in patients with a protracted course of rheumatic fever, with the I degree of the process activity, circulatory disorders and complicated cardiac failures. There was a clearly seen direct relationship between the activity of BGU in the blood serum and the level of circulating immune complexes, and an indirect relationship between the mentioned enzyme and alpha 2-globulin. A decrease in the activity of BGU in the cells was caused by degranulation of neutrophils and monocytes induced by immunological factors. A decrease in the level of BGU in the cells of patients with rheumatic fever apparently influences the processes of phagocytosis and aggravates immunological disorders, and, consequently, is connected with the disease pathogenesis. Determination of the BGU activity in the blood serum can be used for detection of the minimum activity of the inflammatory process in a chronic course of rheumatic fever. PMID- 1925269 TI - Septic arthritis caused by Corynebacterium xerosis following vascular surgery. AB - A case of septic arthritis due to Corynebacterium xerosis occurred after vascular surgery and was successfully treated with intravenous cefotaxime followed by oral erythromycin. The only previously reported case of C. xerosis arthritis developed in a patient with a history of similar recent surgery. The possible association of this infection with such a postsurgical setting is discussed. PMID- 1925270 TI - Bacteremia caused by Enterobacter: 15 years of experience in a cancer hospital. AB - A total of 296 episodes of bacteremia due to Enterobacter occurred in 281 patients with cancer between 1972 and 1986. The majority of these episodes were caused by Enterobacter cloacae. Seventy-four percent of the patients developed their infection while in the hospital and 55% had received therapeutic antibiotics during the 10 days preceding the onset of the infection. Enterobacter bacteremia was associated with shock in 24% of the patients and with disseminated intravascular coagulation in only 3%. The overall rate of response to therapy was 79% and increased to 85% during the last 5-year period. Only five patients remained afebrile during their infection, but four of these five died. Only 37% of the patients with shock responded to therapy compared with 93% of the patients without shock. The rate of response to therapy was 86% among patients without pulmonary infection compared with only 53% among those with pulmonary infection. The response rate to therapy with a single antibiotic was 73% and that to therapy with two antibiotics was 85%. As single therapeutic agents aminoglycosides were less effective than beta-lactam agents. PMID- 1925271 TI - Pleural fluid infection caused by Listeria monocytogenes: case report and review. AB - Nine cases of pleural fluid infection caused by Listeria monocytogenes (one case described here and eight cases previously reported in the literature) were reviewed. Eight patients (88.9%) had an underlying malignancy (three had Hodgkin's disease, three had non-Hodgkin's lymphoma, and two had leukemia), and six (66.7%) were receiving immunosuppressive therapy at the time of presentation. Seven patients (77.8%) presented with fever and five (55.6%) with respiratory tract symptoms. Those with symptoms of greater than 3 weeks' duration had a relatively poor prognosis. Bacteremia was documented in five patients (55.6%). Examination of pleural fluid typically revealed normal levels of glucose, slightly elevated concentrations of protein, and a negative gram stain. Four patients died, for an overall mortality of 44.4%. Mortality appeared to be lower for patients who received a combination of penicillin or ampicillin plus an aminoglycoside and for those who underwent drainage of pleural fluid than for those not given such treatment. Rapid diagnosis, prompt institution of appropriate antimicrobial therapy, and drainage of the pleural fluid are likely to improve the chances for survival in listerial infection of pleural fluid. PMID- 1925272 TI - Rheumatoid arthritis: new findings on the failure to isolate or detect mycoplasmas by multiple cultivation or serologic procedures and a review of the literature. AB - Using 12 different and elaborate broth, agar, and cell culture procedures, we failed to isolate mycoplasmas, ureaplasmas, spiroplasmas, or chlamydiae from the synovial fluid of 10 patients with rheumatoid arthritis (RA) and from six patients with non-rheumatoid arthritis (NRA). In addition, sera from 35 patients with RA and 12 patients with NRA also were examined. Although some of the sera had moderately high titers of metabolism-inhibiting antibody to some of the 10 human Mycoplasma species, especially to the common respiratory pathogen Mycoplasma pneumoniae, and to some of the eight Ureaplasma urealyticum serovars, especially serovars V and VII, there were no significant differences between titers of these antibodies in the two groups of patients. Among RA patients serum antibody titers to M. pneumoniae were 1:32 in five and 1:16 in eight; two patients had higher synovial fluid titers (1:16) than serum titers (1:4). The geometric mean titer (GMT) of antibody to serovar V in synovial fluid was higher in RA patients than in NRA patients, but the difference did not reach significance (P = .056). Reports on the possible role of infectious agents in the pathogenesis of rheumatoid arthritis are reviewed. PMID- 1925273 TI - Infectious complications of hepatic artery catheterization procedures in patients with cancer. AB - A total of 353 hepatic artery catheterization procedures were carried out in 211 patients with cancer over a 1-year period (January-December 1988). The procedures included 49 embolizations in 32 patients, 123 chemoembolizations in 73 patients, and 181 chemoinfusions in 106 patients. The overall infection rate was 3.4%. Infectious complications occurred in 3.1% of patients undergoing hepatic artery embolization alone, 1.9% of patients undergoing hepatic artery chemoinfusion, and 4.1% of patients undergoing hepatic artery embolization followed by chemoinfusion. Four patients had infectious complications that included four episodes each of cholangitis, liver abscess, and septicemia. One patient developed a subphrenic abscess in addition to a liver abscess. Enteric gram negative bacilli (aerobic and anaerobic) were isolated from all four patients. None of the patients had received prophylactic antibiotics. All patients responded to antimicrobial therapy and percutaneous drainage of abscesses. PMID- 1925274 TI - Infections associated with biliary drainage procedures in patients with cancer. AB - A total of 170 therapeutic biliary drainage procedures were carried out in 90 patients with cancer over a 1-year period (January-December 1988). There were 129 percutaneous transhepatic biliary drainage procedures done in 61 patients and 41 endoprostheses were placed in 29 patients. The overall infection rate related to these procedures was 60.6%, the rate being similar for the two procedures. Infectious complications were experienced by 50% of patients undergoing a biliary drainage procedure. The most common manifestation was cholangitis followed by bacteremia. Other infections included liver abscess, gallbladder abscess, and subphrenic abscess. The most common isolates were enteric gram-negative bacilli, followed by Enterococcus species, Candida species, and Staphylococcus epidermidis. The use of prophylactic antibiotics in 76% of infected patients failed to prevent biliary catheter-related infections. Two patients died of complications related to biliary sepsis. All other infected patients responded to antimicrobial therapy, which included various regimens of beta-lactam agents (third-generation cephalosporin, extended-spectrum penicillin, imipenem cilastatin, and aztreonam) that were used in combination with an aminoglycoside in 15 patients. PMID- 1925275 TI - Response to empiric amphotericin B during antileukemic therapy-induced granulocytopenia. AB - We analyzed the initial and overall responses to empiric therapy with amphotericin B as they related to the rate of occurrence and the type of fungal infection and colonization during 264 consecutive episodes of prolonged, profound, chemotherapy-induced bone marrow aplasia (greater than 30 days, less than 100 polymorphonuclear leukocytes/mm3) in 160 adults with acute leukemia. Amphotericin B was administered during 248 (94%) of these granulocytopenic episodes; in 68 cases the drug was given because of documented infection with yeasts or filamentous fungi (DFI), and in 180 cases it was given because of refractory fever without DFI. The frequency of an initial response in patients with DFI (60%) was similar to that in non-DFI-infected patients (61%). Both the initial response rate and the overall survival rate were significantly decreased when therapy with amphotericin B was not initiated empirically before documentation of filamentous DFI. Given the comparatively high rates of initial and overall response (the latter being 74% and 71% for DFI and non-DFI, respectively) and the lack of alternative fungicidal agents, our data support prompt empiric treatment with amphotericin B for refractory fever in adults with acute leukemia who are compromised by severe, therapy-induced granulocytopenia. PMID- 1925276 TI - Enterococcal bacteremia: to treat or not to treat, a reappraisal. AB - The treatment of enterococcal bacteremia not associated with endocarditis has been controversial. We retrospectively reviewed 81 episodes of enterococcal bacteremia and categorized them as to their clinical significance, using a strict case definition. Of the 81 episodes, 41 met our criteria for clinical significance. Mortality was 51% among the 41 patients with clinically significant bacteremia and 50% among the 40 patients with bacteremia of uncertain clinical significance. Despite these equivalent overall mortality figures, antibiotic therapy specific for Enterococcus species was associated with reduced in-hospital mortality among patients with clinically significant infections (relative risk [RR] = 0.46, 95% confidence interval [CI] = 0.27-0.77); mortality was also reduced in the first 7 days after the detection of bacteremia, when death was relatively likely to be directly due to the bacteremic episode (RR = 0.17, CI = 0.04-0.74). The association between appropriate antibiotic therapy and reduced mortality remained statistically significant when adjustments were made for a number of other factors related to mortality, including age, underlying conditions, prior use of antibiotics, nosocomial acquisition, polymicrobial etiology, prior surgery, and source of infection. Thus enterococcal isolates from the blood, even when of doubtful clinical significance, are poor prognostic markers associated with high mortality. However, when the clinical significance of bacteremia is defined by strict criteria, specific therapy against Enterococcus species is associated with improved outcome. PMID- 1925277 TI - Pott's puffy tumor: a complication of intranasal cocaine abuse. AB - The increasing intranasal abuse of cocaine has been associated with numerous medical problems. Among the most common complications are chronic sinusitis and septal perforation, although myocardial infarction and death also have been reported. We describe the development of Pott's puffy tumor in a patient who chronically abused cocaine. Pott's puffy tumor, a subperiosteal abscess of the frontal bone associated with frontal osteomyelitis, is a rare complication of frontal sinusitis. This case report underscores the dangers of cocaine abuse and describes yet another potentially serious sequela. PMID- 1925278 TI - Haemophilus parainfluenzae as a rare cause of epidural abscess: case report and review. AB - We report a case of epidural abscess due to Haemophilus parainfluenzae. This microorganism is a normal inhabitant of the upper respiratory tract that causes endocarditis and, rarely, other invasive infections. To the best of our knowledge, epidural abscess due to H. parainfluenzae has not been reported previously. A 74-year-old man presented with neck pain and subsequently developed incomplete quadriparesis. A cervical epidural abscess and vertebral osteomyelitis were detected by radiologic studies. Surgical drainage and antibiotic therapy resulted in resolution of the abscess and osteomyelitis, and the neurologic sequelae were minimal. Cultures of the purulent material from the abscess yielded H. parainfluenzae. Descriptions in the literature of infections caused by H. parainfluenzae and the antimicrobial agents used for treatment of these infections are reviewed. PMID- 1925279 TI - Bacteremia in granulocytopenic patients in a tertiary-care general hospital. AB - Episodes of bacteremia in granulocytopenic patients during 1985 and 1986 at a tertiary-care general hospital were reviewed to assess the adequacy of current empiric antimicrobial therapy. The major pathogens in these cases were Pseudomonas aeruginosa, Enterobacteriaceae organisms, and Staphylococcus epidermidis. This combination of pathogens differed from that found at the same facility from 1975 to 1977, when Staphylococcus aureus and streptococci predominated. When apparent, the sources of infection were predominantly venous catheters, the lower respiratory tract, and the urinary tract; most frequently there was no identifiable focus. S. epidermidis and streptococci were isolated more frequently during initial episodes of febrile bacteremia, and P. aeruginosa was isolated more often during subsequent episodes. If a narrow definition for therapeutic outcome is used, only 38% of episodes had a favorable response; response rates were no different with appropriate or inappropriate therapy. The low response rate may have been related to the use of data from the previous review to guide empiric therapy and to the subsequent inadequate treatment of infections caused by Pseudomonas and Enterobacter organisms. The overall mortality per total bacteremic episodes was 19%, and the primary factor associated with mortality was pneumonia (P less than .0001). This study emphasizes the need for ongoing surveillance of local patterns of bacteremia to direct empiric therapy. PMID- 1925280 TI - Septic endarteritis of the femoral artery following angioplasty. AB - A case of septic endarteritis that occurred in the femoral artery following percutaneous transluminal coronary angioplasty (PTCA) is reported, and nine previously reported cases of this complication are reviewed. In each case Staphylococcus aureus was identified as the pathogen. For all cases in which a complete clinical description was available, endarteritis occurred following repeated PTCA or repuncture PTCA (i.e., a second catheterization at the original site of insertion for diagnostic purposes). The characteristic manifestations of endarteritis in this setting included bacteremia (all 10 cases), the formation of a pseudoaneurysm (six), distal emboli (five), and regional septic arthritis or osteomyelitis (five of six cases that included the information needed to determine the presence of these conditions). In each case, treatment included 4-6 weeks of iv antibiotics and surgery, most frequently resection of the pseudoaneurysm and vascular bypass. We recommend surveillance for the signs of endarteritis, especially after repeated catheterization, and use of the contralateral site when repeated catheterization is indicated. When the ipsilateral site is used, the administration of prophylactic antibiotics should be considered. PMID- 1925281 TI - Nocardial infection as a complication of AIDS: report of six cases and review. AB - Nocardiosis has been increasingly recognized as a serious infection among persons who otherwise appear healthy and among those with underlying chronic disease, neoplasms, and immunosuppression. Nocardial infection as a complication of AIDS has been reported infrequently. Six patients with AIDS and nocardiosis were identified at one New York City hospital from January 1980 through March 1989. Sites of nocardial infection in these patients included the lungs, brain, esophagus, and suprarenal and paraspinal masses. Mycobacteria, fungi, viruses, and bacteria other than Nocardia species caused concomitant infections in three patients. Three patients died of nocardiosis. Because of such factors as the growth properties of Nocardia species, the presence of other organisms, the common use of sulfonamides for treatment of patients with AIDS, and a low index of suspicion among physicians, the incidence of nocardiosis as a complication of AIDS may possibly be underreported. Early recognition of nocardial infection may lead to an improved prognosis. PMID- 1925282 TI - Nocardial brain abscesses in a pregnant woman. AB - We describe what we believe to be the second case in which a pregnancy was complicated by the formation of brain abscesses due to Nocardia asteroides; this case may be the first one in which no risk factor for the infection (other than the pregnancy itself) could be found. Craniotomy with surgical drainage of the abscesses, combined with prolonged antimicrobial therapy, led to clinical cure in the mother, and she gave birth to an unaffected infant. This case illustrates the difficulty in treating a nocardial infection of the brain during pregnancy as well as the importance of achieving adequate surgical drainage of the abscesses. PMID- 1925283 TI - Anaerobic bacteremia: decreasing rate over a 15-year period. AB - At the Mayo Clinic, the number of cases of anaerobic bacteremia decreased 45% between 1974 and 1988. In addition, the percentage of blood cultures positive for anaerobes decreased significantly even though the total number of blood cultures performed increased. The number of anaerobic bacteremias per 100,000 patient-days also declined over the 15-year period. Organisms of the Bacteroides fragilis group ranked third in frequency with respect to other organisms that caused aerobic and anaerobic bacteremia in 1974 but ranked only seventh in 1988 and caused slightly less than one-half of the anaerobic bacteremias. The mechanisms responsible for these changes are unclear but might relate to earlier recognition and treatment of localized anaerobic infection, widespread preoperative use of agents prior to bowel surgery, and use of broad-spectrum antimicrobial regimens that include agents with activity against anaerobes. PMID- 1925284 TI - Role of bronchoalveolar lavage in diagnosis of disseminated toxoplasmosis. AB - In three cases of acute disseminated toxoplasmosis developing soon after renal (two patients) or hepatorenal (one patient) transplantation, Toxoplasma gondii trophozoites were visualized on Giemsa-stained smears of bronchoalveolar lavage fluid. Trophozoites were also found in bone marrow smears in one instance. Seroconversion occurred late in two cases and was not detected before the patient's death in the third. These observations underline the potential of bronchoalveolar lavage as a diagnostic procedure for disseminated toxoplasmosis. PMID- 1925285 TI - Cellulitis due to Pseudomonas putrefaciens: possible production of exotoxins. AB - Pseudomonas putrefaciens has been described as a rare cause of both lower-limb cellulitis and septicemic illness with significant morbidity. We report a case of P. putrefaciens infection in a patient with refractory lower-limb cellulitis and ulceration complicated by thrombocytopenia, hypotension, and mental obtundation in the apparent absence of bacteremia. This scenario raises the possibility of significant production of exotoxins by P. putrefaciens in vivo. PMID- 1925286 TI - Rabies in Thailand: 1990. AB - Of the more than 100,000 courses of postexposure rabies treatment given in Thailand annually, 95% consist of brain tissue-derived vaccine without immune globulin. Rabies tissue culture vaccines and immune globulins are expensive by the standards of developing countries. When they are given according to either of two proven intradermal postexposure schedules, significant savings can be achieved without loss of efficacy. Purified equine rabies immune globulins account for approximately 10% of the cost of human products administered to exposed individuals and have been shown to be safe and effective. A canine preexposure immunogenicity study with a potent, inactivated tissue culture vaccine revealed that 12.5% of Thai dogs failed to develop protective antibody titers 2 months after one subcutaneous injection. Previous studies have shown significant antigenic differences between Thai street rabies virus and European and North African strains. PMID- 1925287 TI - Aspergillosis of the CNS in a pediatric liver transplant recipient: case report and review. AB - A 2-month-old infant who had undergone orthotopic liver transplantation at the age of 2 weeks for carbamoyl phosphate synthetase deficiency developed infection of the CNS due to Aspergillus fumigatus. The patient was successfully treated with administration of a combination of antifungal agents (including intraventricular amphotericin B), drainage of the parietal lobe abscess, and cessation of immunosuppression. An intraventricular catheter was used both to obtain ventricular fluid for microbiologic testing and to deliver amphotericin B during nearly 4 months of treatment. We review literature on aspergillosis in solid-organ transplant recipients, especially those in whom the disease involves the CNS, and discuss in particular clinical presentation, diagnosis, treatment, and outcome. PMID- 1925288 TI - Plagues--what's past is present: thoughts on the origin and history of new infectious diseases. AB - Medical science has made tremendous strides in overcoming infectious diseases in the 20th century. Despite this, several epidemics of previously unrecognized diseases have occurred during the last 15 years. These diseases include Lyme disease, Legionnaires' disease, toxic shock syndrome, and AIDS. Examination of past epidemics, including the plague of Athens, the black death, syphilis, and influenza, suggests that the sudden occurrence of diseases that were previously unrecognized is not unusual. Analysis of the new infectious disease indicates that while all four appeared suddenly, isolated cases of the disease occurred before the actual epidemic. Further, all four new diseases were found to be due to agents or toxins that were not previously recognized. Epidemics due to new infectious diseases may arise by several mechanisms, including mutation of the pathogen to a virulent form and introduction of an infectious agent into a nonimmune population. Environmental and behavioral factors may play an important role, as illustrated by toxic shock syndrome, Legionnaires' disease, and AIDS. On the other hand, epidemic diseases tend to abate over time because of changes in the infecting pathogen and in the host. Hence, epidemics can be seen as cycles; new diseases will arise periodically, occasionally with a devastating outcome. With time the effects of these diseases on the population will ameliorate. The cycle will begin again when a new disease emerges. PMID- 1925289 TI - Houseflies (Musca domestica) as mechanical vectors of shigellosis. AB - Houseflies (Musca domestica) are mechanical vectors of Shigella organisms. Seasons during which both flies and cases of dysentery are prevalent often coincide. Houseflies have an affinity for human excrement and, as documented by bacteriologic culture of trapped flies, become contaminated with Shigella organisms following contact with infected human feces. The inoculum required to transmit shigellosis is only 10-10(2). Since houseflies cohabit with humans, they can readily contaminate food and eating utensils. With the advent of insecticides in the 1940s, intervention studies in the United States provided evidence of the role of the housefly in transmission of shigellae. In towns that were exposed to fly-control measures, the density of flies and the prevalence of carriage of Shigella organisms, diarrhea, and mortality due to diarrheal disease among young children all markedly diminished as compared with the situation in control towns. Investigations that quantitate the importance of fly-borne transmission of Shigella organisms relative to other modes of transmission and that provide evaluation of measures to diminish fly-borne transmission are warranted in developing areas. PMID- 1925290 TI - Adverse virus-drug interactions. AB - Over the last 3 decades, epidemiologists and clinicians have identified a few clinical entities that appear to result when a viral infection and a chemical exposure overlap and interact. Ampicillin rash during infectious mononucleosis, Reye's syndrome following salicylate ingestion and certain viral infections, and the association of AIDS-related Kaposi's sarcoma with abuse of nitrite inhalants and infection due to human immunodeficiency virus are examples of such phenomena. Preclinical research provides additional evidence that viruses and chemicals may interact and produce illnesses in animals. We hypothesize that other virus-drug interactions may exist. Identifying such interactions may lead to a better understanding of the pathogenesis of currently baffling illnesses and may provide insights into ways of preventing and/or treating diseases that appear uncontrollable now. PMID- 1925292 TI - Stress and pathogenesis of infectious disease. AB - Despite inherent difficulties in defining and measuring stress, a scientific framework has been provided in recent years for understanding how disruptive life experiences might be translated into altered susceptibility to infectious diseases. Studies of the effects of stress on pathogenesis of infectious disease are highly relevant to assessment of the biological importance of the immune impairments that have been associated with stress. With a few notable exceptions, investigations of viral infections in humans and in animal models support the hypothesis that stress promotes the pathogenesis of such infections. Similar conclusions can be drawn from studies of bacterial infections in humans and animals and from a small number of studies of parasitic infections in rodent models. While many of these studies have substantial limitations, the data nonetheless suggest that stress is a potential cofactor in the pathogenesis of infectious disease. Given recent unprecedented advances in the neurosciences, in immunology, and in the field of microbial pathogenesis, the relationship between stress and infection should be a fruitful topic for interdisciplinary research. PMID- 1925291 TI - Pulmonary manifestations of leptospirosis. AB - Pulmonary involvement in leptospiral infection is common, usually mild, and often overlooked. When pulmonary manifestations are prominent in a patient with leptospirosis, there is the potential for diagnostic confusion. We present the case of a patient with adult respiratory distress syndrome secondary to leptospirosis and review the pulmonary manifestations of leptospiral infection. PMID- 1925293 TI - Acute neurologic deterioration in a young man. PMID- 1925295 TI - Infectious diseases as a subspecialty in Canada: status of the practice in Quebec. PMID- 1925294 TI - Role of antibodies and antibiotics in aerobic gram-negative septicemia: possible synergism between antimicrobial treatment and immunotherapy. AB - Recovery from gram-negative septicemia depends on the successful joint action of antibiotics and host defense mechanisms. The possible enhancement of host defense with either immunotherapy or antibiotic treatment has been the subject of numerous investigations. Because of the great similarity of core epitopes within different species of Enterobacteriaceae, most studies have focused on the development of cross-reactive and/or cross-protective antibodies to these common epitopes. The majority of strains that cause severe gram-negative septicemia, however, possess a complete O antigen (and often a K antigen) that may camouflage the common antigenic determinants. Antibodies to these common antigens therefore may be unable to recognize their targets. Subinhibitory concentrations of certain antibiotics have been shown to alter surface structures of Enterobacteriaceae to such an extent that the structures no longer camouflage underlying epitopes, allowing binding of cross-reactive or cross-protective antibodies to these epitopes. Thus antibiotics and antibodies may synergistically fight infection. PMID- 1925296 TI - Infections due to Xanthomonas maltophilia in patients with hematologic malignancy. PMID- 1925297 TI - Exchange transfusion for malaria: what are the indications? PMID- 1925298 TI - Infections due to Balantidium coli in primates. PMID- 1925299 TI - Penicillium marneffei: another pathogen to consider in patients infected with human immunodeficiency virus. PMID- 1925300 TI - Brain abscess caused by Listeria monocytogenes. PMID- 1925301 TI - Vertebral osteomyelitis due to Branhamella catarrhalis. PMID- 1925302 TI - Pneumonia due to Bordetella bronchiseptica in a patient with AIDS. PMID- 1925303 TI - Cefazolin-induced encephalopathy in uremic patients. PMID- 1925304 TI - Pericarditis due to Bacillus cereus in an intravenous drug user. PMID- 1925305 TI - Isoniazid-induced toxic fever. PMID- 1925306 TI - Adherence of Helicobacter pylori to gastric carcinoma cells: analysis by flow cytometry. AB - An in vitro assay using immunofluorescence and flow cytometry for quantitative assessment of the adherence of Helicobacter pylori to cultured human gastric carcinoma (KATO III) cells was developed. Adherence was rapid, saturable, energy dependent, mannose resistant, and significantly inhibited by fetuin, a glycoprotein containing N-acetylneuraminyllactose. Pretreatment of KATO cells with neuraminidase from Clostridium perfringens, however, did not reduce adherence of H. pylori. Ultrastructurally, adherent cells of H. pylori were associated with indentations of KATO cell membranes. KATO cells should prove useful in the investigation of mechanisms of adherence of H. pylori to mammalian cells. Ultimately, this flow cytometric assay may be helpful in assessment of the adherence of laboratory strains of H. pylori directly to surface mucous cells dissociated from biopsied human gastric tissue. PMID- 1925307 TI - Elevation of meal-stimulated gastrin release in subjects with Helicobacter pylori infection: reversal by low intragastric pH. AB - The aim of the present study was to determine whether the association between Helicobacter pylori infection and increased concentrations of gastrin in serum is independent of chronic duodenal ulcer disease and whether the mechanism of this association involves a disturbance of feedback inhibition of gastrin release by intragastric acid. Of 48 subjects evaluated, 26 (54%) were seropositive for H. pylori by ELISA. Fasting and peptone meal-stimulated gastrin release at pH 2.5 and pH 5.5 as well as integrated 24-hour plasma gastrin concentrations were significantly higher in the seropositive group, even when subjects with a history of duodenal ulcer were excluded. The inhibitory effect of low pH on the release of gastrin was not attenuated in subjects with positive results in the ELISA. These data indicate that the association between seropositivity for H. pylori and enhanced release of gastrin is independent of a history of duodenal ulcer and is not caused by a disturbance of the normal feedback inhibition of gastrin release by intragastric acid. PMID- 1925308 TI - Gastritis induced by Helicobacter pylori in gnotobiotic piglets. AB - Helicobacter pylori has recently been recognized as a gastric pathogen in humans. Experimental oral inoculation of gnotobiotic piglets with this organism results in gastritis that exhibits many features of the corresponding disease in humans. In piglets the organism is restricted to the gastric microenvironment and persists in that location despite prompt humoral and cellular responses to antigens of H. pylori. The gnotobiotic piglet model is useful for delineation of the role of suspected bacterial virulence factors (i.e., motility and urease production) in gastric colonization and for preclinical determination of the efficacy of various antimicrobial substances. PMID- 1925309 TI - Production of a cytotoxin by Helicobacter pylori. AB - Helicobacter pylori produces a cytotoxin that was initially detected as the ability of broth culture filtrates of this bacterium to induce intracellular vacuolation of cultured cells. Fifty-three percent of more than 200 isolates of H. pylori tested produce the cytotoxin, which appears to be unique to H. pylori. Results of characterization studies suggest that the cytotoxin is a high molecular-weight protein. Detection of serum antibody to the cytotoxin by neutralization or immunoblotting indicates that this toxin is produced in vivo. The cytotoxin is more frequently associated with cases of peptic ulceration than with cases of gastritis; this finding suggests that the toxin contributes to the severity of disease associated with H. pylori infection. PMID- 1925310 TI - Pharmacology of bismuth-containing compounds. AB - Bismuth compounds have been used for more than two centuries. A review of the modes of action, pharmacokinetics, and toxicity of two commonly used compounds, colloidal bismuth subcitrate and bismuth subsalicylate, is presented. In humans bismuth toxicity is unlikely when therapeutic doses of these compounds are administered for the appropriate duration. The recent use of bismuth compounds to eradicate infection with Helicobacter pylori and to prevent travelers' diarrhea has resulted in scientific reevaluation of these agents. PMID- 1925311 TI - Helicobacter pylori in patients with nonulcer dyspepsia. AB - The relationship between endoscopically diagnosed gastroduodenitis, histologically confirmed gastritis, and symptoms of dyspepsia remains unclear. Marked histologically confirmed inflammation of gastric mucosa often occurs in a stomach that appears normal by endoscopy. Both histologically confirmed and endoscopically diagnosed gastritis are commonly blamed as causes of nonulcer dyspepsia (NUD), although neither disease has been convincingly shown to cause NUD. Helicobacter pylori infection of gastric mucosa is a common cause of histologically confirmed inflammation. It is unclear whether this infection with H. pylori and the resultant gastric mucosal inflammation cause symptoms since inflamed mucosae are also common in asymptomatic controls. The reported increased prevalence of H. pylori in patients with NUD compared with controls suggests a possible causative role in at least a subset of patients with NUD. In addition, three controlled studies of treatment with bismuth demonstrated a significant trend toward improvement of symptoms after clearance of H. pylori. However, two studies of therapy with bismuth failed to demonstrate improvement of symptoms. Further study of patients with NUD is needed to clarify this possible association. PMID- 1925312 TI - Diagnosis of gastritis caused by Helicobacter pylori in children by means of an ELISA. AB - In this study, the systemic immune response to bacterial cell sonicates of Helicobacter pylori was characterized in children with symptomatic gastroduodenal disease. Isotype-specific antibodies to H. pylori in samples of serum from 16 children with culture-proven disease caused by H. pylori and from 19 controls with negative cultures were measured by ELISA with bacterial cell lysates. The levels in serum of IgA antibody to cell sonicates of H. pylori were significantly higher in the patients with positive cultures than in the controls. Only 45% of patients were infected when the established optical density cutoff was used to discriminate between patients infected and not infected with H. pylori. Levels of IgM antibody in serum were not significantly higher in patients who were infected with H. pylori. On the basis of this survey and of previous work conducted in our laboratory, we conclude that at a serum dilution of 1:800, IgG but not IgA or IgM antibody to H. pylori is useful in the rapid screening of symptomatic children for the presence of H. pylori. PMID- 1925314 TI - Characterization of strains of Helicobacter pylori: one-dimensional SDS-PAGE as a molecular epidemiologic tool. AB - One-dimensional linear sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total proteins, coupled with a computerized numerical analysis, was used to distinguish among strains of Helicobacter pylori. One hundred seventy-five clinical strains and five reference strains of H. pylori from humans, four isolates of Helicobacter mustelae from ferrets, and three isolates of H. pylori like organisms (HPLOs) from miniature swine were examined. Intraspecies and interspecies comparisons were made through a numerical analysis of protein profiles. It was possible to make valid comparisons for strains run on a single gel. However, variations between gels were significant in some cases, and strains from these gels were not compared. Multiple isolates of H. pylori from one patient clustered at greater than 90% similarity. All strains of H. pylori clustered at greater than 60% similarity, whereas H. pylori was clearly distinguishable (less than 40% similarity) from both H. mustelae and HPLOs. An eventual application of this technique will be to determine whether relapse following therapeutic intervention is due to reinfection (from an exogenous source) or to recrudescence. PMID- 1925313 TI - Association of infection due to Helicobacter pylori with specific upper gastrointestinal pathology. AB - The association of infection with Helicobacter pylori and antral (type B) gastritis now is clear, and the development of sensitive and specific serologic assays for IgA and IgG allows for diagnosis of this infection by noninvasive means. With use of these assays, we studied the association of infection with H. pylori and four other upper gastrointestinal inflammatory conditions: Barrett's esophagus, pernicious anemia (which accompanies type A gastritis), and duodenal and gastric ulcers. H. pylori was present in only 39% of 41 patients with Barrett's esophagus whose gastric biopsy specimens were examined histologically. Each serologic assay correctly categorized 39 (95.1%) of the 41 patients. For both assays the frequency of seropositivity noted for 58 patients with Barrett's esophagus was not different from that noted for age- and sex-matched healthy controls. Among 40 patients with pernicious anemia, the results of assays for IgA and IgG were positive for 17.5% and 0%, respectively; these prevalences were significantly less than the 50% (IgA) and 40% (IgG) positivities noted for matched controls (P less than .01 for each; McNemar's test). Among 57 patients with documented duodenal or gastric ulcers, the results of assays for IgG and IgA were positive for 100% and 98.2%, respectively; these prevalences were significantly higher than the rate noted for matched controls (P less than .001 for duodenal ulcers and P = .02 for gastric ulcers for IgA assay). These data suggest that infection with H. pylori is strongly associated with duodenal and gastric ulcers, negatively associated with pernicious anemia, and independent of Barrett's esophagus. PMID- 1925315 TI - Gastritis associated with infection by Helicobacter pylori: comparative pathology in humans and swine. AB - Infection of humans with Helicobacter pylori elicits a multifocal, active, chronic inflammatory response and moderate to severe atrophy of the gastric mucosa. Currently, piglets are the only reported animal model of H. pylori infection. Our objective was to compare the inflammatory response induced in humans with that induced in piglets by H. pylori infection. Samples of gastric mucosa were obtained from H. pylori-infected and uninfected piglets and humans. The composition of the inflammatory cell infiltrate and mucosal atrophy were evaluated by histomorphometric analysis of the biopsied gastric tissue. Infection with H. pylori resulted in a three-fold increase in the volume of inflammatory cells in the gastric mucosa of both humans and piglets. In H. pylori-infected humans, neutrophils composed the bulk of the cellular infiltrate; in piglets, the primary inflammatory cell was the lymphocyte. Both humans and piglets had severe epithelial cell vacuolation and significant reduction of the gastric mucosal surface area. We concluded that pathologic processes induced by infection with H. pylori, which include relatively severe mucosal inflammation, mucosal atrophy, and epithelial vacuolation, are similar in piglets and humans but that the primary inflammatory cell types are distinctly different in the two species. PMID- 1925316 TI - Beta-lactamase inhibition: therapeutic implications in infectious diseases--an overview. PMID- 1925317 TI - Ticarcillin-clavulanate therapy for bacterial skin and soft tissue infections. AB - Ticarcillin-clavulanate is active in vitro against the vast majority of pathogens involved in skin and soft tissue infections. A compilation of six controlled clinical trials of ticarcillin-clavulanate for treatment of skin infections showed a satisfactory clinical response in 175 (93%) of 189 cases. The bacteriologic response included eradication of Staphylococcus aureus, Enterococcus species, Enterobacteriaceae, and Pseudomonas aeruginosa in 88%, 75%, 88%, and 77% of cases, respectively. In addition, the records of 17 patients with diabetic foot infections who were treated with ticarcillin-clavulanate as monotherapy in controlled trials are reviewed. Eight of these infections were cured and eight were improved at the end of therapy. The available clinical data suggest that ticarcillin-clavulanate is effective antimicrobial therapy for skin infections. PMID- 1925318 TI - Aspiration pneumonia. AB - The primary problems that predispose to aspiration pneumonia include a reduced level of consciousness, dysphagia, periodontal disease, and mechanical interference that is related to the insertion of various tubes into the respiratory or gastrointestinal tracts. The bacterial flora involved include the indigenous oral flora (among which anaerobes predominate) and, in the hospital or a similar setting, nosocomially acquired pathogens such as Staphylococcus aureus and various aerobic and facultative gram-negative bacilli that may colonize patients. Specific etiologic diagnosis is difficult. The most useful materials for reliable anaerobic and aerobic culture are pleural fluid, transtracheal aspirates, and secretions obtained with a protected bronchial brush and during bronchoalveolar lavage. Special care must be taken to avoid normal and colonizing flora and to keep anaerobes viable. Aside from the drainage of empyemas, the primary therapy for aspiration pneumonia involves antimicrobial agents. A number of options are available; the most appropriate mode of therapy depends on the nature of the infecting flora and the severity of the illness. PMID- 1925319 TI - Nosocomial pneumonia: pathogenesis and recent advances in diagnosis and therapy. AB - Despite recent progress in the prevention and treatment of hospital-acquired infections, nosocomial pneumonia remains an important problem among critically ill patients. Nosocomial pneumonia develops in five to 10 patients per 1,000 admissions and has a mortality rate of 20%-50%. This review focuses on three areas of nosocomial pneumonia that have been the subject of investigation in recent years: (1) pathogenesis, especially the role of gastric colonization with gram-negative bacilli in retrograde pharyngeal spread; (2) diagnosis, particularly by means of bronchoalveolar lavage and the protected specimen brush during bronchoscopy; and (3) therapy with extended-spectrum penicillins, third generation cephalosporins, imipenem, aztreonam, and quinolones. PMID- 1925320 TI - Antibiotic therapy for postcesarean endomyometritis. AB - Puerperal uterine infection, or endomyometritis, occurs more commonly after cesarean section than after vaginal birth. With the rate of cesarean delivery almost 25% of all births in this country, such infection is relatively common. The classic therapy for postcesarean endomyometritis is the combination of clindamycin and an aminoglycoside, usually gentamicin or tobramycin. This regimen has requisite antimicrobial activity against the aerobes and anaerobes of the cervicovaginal flora that usually cause this illness. In the last decade, however, the availability of broad-spectrum beta-lactam antibiotics has enabled the clinician to combat postcesarean infection with single-agent antimicrobial chemotherapy, or monotherapy. "Higher-generation" cephalosporins such as cefoxitin, cefotetan, and moxalactam, as well as the semisynthetic penicillins ticarcillin, piperacillin, and mezlocillin, have all been used alone in the therapy for postpartum infection. The addition of a beta-lactamase inhibitor to this class of drugs now offers a further resource to the practitioner if beta lactamase-mediated antibiotic resistance arises in the patient population being treated. PMID- 1925322 TI - Empiric therapy for the immunocompromised host. AB - The use of empiric therapy for immunocompromised hosts has been one of the major advances in the management of such patients. Such therapy has been put into practice primarily for patients with neutropenia induced by cytotoxic chemotherapy. The empiric antibiotic regimens include in their coverage the bowel, skin, and intravenous-catheter flora anticipated for patients in a particular hospital. Less often, physicians treat empirically for opportunistic infections that complicate defects in helper cells, although empiric therapy for presumed Pneumocystis carinii pneumonia and Toxoplasma gondii infection of the central nervous system has become commonplace for patients infected with human immunodeficiency virus. Physicians also should consider environmental factors that expose patients to certain opportunistic organisms. Examples of such pathogens include Mycobacterium tuberculosis and Histoplasma capsulatum. The particular microorganisms considered to be opportunistic vary in different parts of the world and in different hospitals, and their designation as such may change rapidly. Multiple environmental exposures and immune defects, rather than just one factor, may be responsible for opportunistic infections and should be investigated and taken into account when empiric therapy is planned. Preventive measures, including simply rigorous hygiene, should precede and may obviate the need for empiric therapy. PMID- 1925321 TI - Ticarcillin/clavulanate for treatment of postpartum endometritis. AB - Postpartum endometritis continues to be the leading cause of morbidity following cesarean section. This infection is commonly polymicrobial, involving aerobic, facultative, and obligate anaerobic gram-negative bacteria as well as gram positive bacteria. The major risk factor for the development of post-cesarean section endometritis is duration of labor with ruptured amniotic membranes of greater than 6 hours. The most frequently utilized antibiotic regimen employed for treatment of postpartum endometritis is the combination of clindamycin and gentamicin. The combination ticarcillin/clavulanate has a spectrum of activity resembling that of clindamycin and gentamicin. In the data reported, cure rates among patients treated with ticarcillin/clavulanate were similar to the rates for those treated with clindamycin plus gentamicin as well as those for cefoxitin. PMID- 1925323 TI - Strategic antibiotic decision-making at the formulary level. AB - The proliferation of antimicrobial agents introduced for the treatment of increasingly complex infectious diseases, coupled with the obligation to provide the best possible medical care in keeping with hospital fiscal constraints, has created a need for strategic decision-making about antibiotics at the formulary level. The following experience at the Hartford Hospital, a 1,000-bed tertiary care facility, represents an example of an antibiotic management system based on a multidisciplinary approach that utilizes infectious disease physicians, clinical microbiologists, hospital epidemiologists, and pharmacists. PMID- 1925324 TI - Tips for avoiding claim delays. PMID- 1925325 TI - Improving patient acceptance of treatment plans. PMID- 1925326 TI - [The research protocol (II). The administrative aspects and sources of financing]. PMID- 1925327 TI - [Primary health care: an analysis of the nursing work (II)]. PMID- 1925328 TI - [Burns. Their treatment and classification]. PMID- 1925329 TI - [The determination of standards of nursing care]. PMID- 1925331 TI - [Nursing: AIDS and "counselling". A new role for our profession: advising]. PMID- 1925330 TI - [Spanish hospital nursing maintains a status superior to the British one]. PMID- 1925332 TI - [Presentation of the framework document for developing the health plan of Catalonia]. PMID- 1925333 TI - [Therapeutic compliance. Some considerations]. PMID- 1925334 TI - [Cutting wounds caused by vials. The most frequent accident]. PMID- 1925335 TI - [An approach to narcolepsy]. PMID- 1925337 TI - [Meals on wheels]. PMID- 1925336 TI - [Biological changes in the skin]. PMID- 1925339 TI - [New roles for nursing]. PMID- 1925338 TI - [Continuing education. 59. Subject: basic nursing. Topic: the theoretical bases of nursing]. PMID- 1925340 TI - AIDS vaccine boosts immunity in HIV patients. PMID- 1925341 TI - Should the Feds provide needles to drug users? PMID- 1925342 TI - Practice makes perfect. PMID- 1925343 TI - When even the best isn't good enough. PMID- 1925344 TI - Assessing headache pain. PMID- 1925345 TI - When to suspect septic shock. PMID- 1925346 TI - Nurses in the Gulf. AB - A year ago, the nurses of the 18th Airborne COSCOM, 44th Med Brigade, 5th Mobile Army Surgical Hospital Unit, and the 46th Combat Support Hospital with the 24th Infantry Division arrived in the Saudi Arabian desert. Their experiences left some of them challenging accepted stateside nursing procedures. PMID- 1925347 TI - BRMs. New drug therapy comes of age. PMID- 1925348 TI - 1991 earnings survey. Nurses are worth more than ever. PMID- 1925349 TI - Expect to hear about unions. PMID- 1925351 TI - Can a "good" HIV strain reduce AIDS patients' suffering? PMID- 1925350 TI - Fertility and diet. PMID- 1925352 TI - [Anatomy and etiology of aortic aneurysms]. AB - The term "aortic aneurysm" applies to numerous conditions with extremely varied anatomical and aetiological features, which consist of more or less complete and localized destruction of the aortic wall components resulting in a sacciform or fusiform distension induced by blood pressure, with loss of parallelism between the sides of the aorta. The most frequent aneurysms, leading to numerous cardiovascular operations, are encountered mainly in middle-aged men. These aneurysms complicate the infra-renal terminal atherosclerosis of smokers or the parietal elastic dystrophy of the ascending aorta, where a few subjects in their twenties with Marfan's disease join the older men, and which clinically presents as severe aortic incompetence. The aneurysm of syphilis and its destructive effect on thoracic structures is a thing of the past with a purely historical interest. Dissecting aneurysms--which should be called incomplete internal aortic disease with delamination of the media--remains a fearsome disease in subjects over 50, despite advances in surgery. Rare types of aneurysm (traumatic, infectious, or local accentuation of megadolichoarteries, aortitis or connective tissue dysgenesis) complete the list. PMID- 1925353 TI - [Contribution of imaging to the study of aortic aneurysms]. AB - All aortic aneurysms require a positive diagnosis, a differential diagnosis and an assessment of extension. Several exploratory methods can be contemplated. In patients with warning symptoms, conventional radiology may point to the diagnosis. The reference method remains retrograde aortography which may be either conventional and seriographic or, better, radiocinematic with orthogonal projections and, if possible, digital. The site and morphology of the aneurysm, and in particular its inner channel are thus demonstrated. Computerized tomography is less invasive and usually of great value, notably for the horizontal, thoracic and abdominal aorta, not only to confirm the diagnosis but also to determine the size of the inner channel, parietal thrombi and aortic walls, as well as relations with nearby structures. Other, totally non-invasive methods are widely utilized to explore aortic aneurysms. These are ultrasonography and its variants (notably Doppler-echocardiography and the transoesophageal route), and magnetic resonance imaging which provides three dimensional and anatomical views of the vessel. These last two examinations alone usually confirm and outline the aortic aneurysms. They must therefore be utilized as first-line examination, arteriography it is various forms being reserved for emergencies or special cases. PMID- 1925354 TI - [Acquired aneurysms of the infrarenal abdominal aorta]. AB - Abdominal aortic aneurysms (AAA) are the result of a degenerative process of the aortic wall. The incidence of AAA has increased during the last three decades. Computerized axial tomography is the best method for investigating AAA. For aneurysms of 4-5 cm or more in antero-posterior diameter, the risk of rupture is definitely high and justifies a preventive surgery. Precise evaluation of myocardial function and of coronary circulation may limit the operative risk and may improve the life expectancy. Screening of AAA in populations at risk will allow to survey the natural history of aneurysmal disease and limit the incidence of rupture which keeps a high mortality rate. PMID- 1925355 TI - [Dissecting aneurysms of the aorta: from causes to therapeutic indications]. AB - In its acute phase, aortic dissection (a term that is now preferred to dissecting aneurysm of the aorta) is a medico-surgical emergency. The diagnosis is suspected on clinical data: intensive thoracic pain with recently appeared diastolic murmur and abolition of a peripheral pulse, contrasting with an electrocardiogram that is either normal or not suggestive of acute coronary thrombosis. It is confirmed by imaging methods, notably echocardiography and/or angiography. These methods, rapidly performed in all circumstances, provide the surgeon with useful information on the size and extent of the dissection and on its complications. Surgery still is the only effective treatment of dissections involving the ascending aorta. In dissections of the descending aorta it may or may not be envisaged, depending on the results of medical treatment. In chronic aortic dissections, which may have a long course, surgery is not mandatory, byt it is necessary in case of mediastinal compression or severe aortic insufficiency. PMID- 1925356 TI - [Infected aneurysms of the aorta]. AB - Mycotic aneurysms, a quite rare syndrome, are classified into three groups: primary (the most frequent one), secondary to bacterial endocarditis, and secondary to direct inoculation (infections focus or trauma). Primary aneurysms are related to bacteremia with bacterial setting of an atheromatous lesion, most often. Clinical presentation is often misleading or delayed from infectious process. However, presence of clinical aneurysm, pain, and infectious syndrome should suggest diagnosis and lead to immediate antibiotic therapy and rapid surgical management, as rupture of the aneurysm is a frequent, serious and ineluctable complication. Importance of microbiologic search is to be emphasized as the diversity of the responsible microorganisms is very high; waiting for bacteriological results, a bactericidal double antibiotherapy should be instituted. PMID- 1925357 TI - [Chronic post-traumatic aneurysms of the thoracic aorta]. AB - Chronic traumatic aneurysms of the thoracic aorta are dilatations resulting from a rupture of isthmus unknown at the time of the trauma. They are observed inn youngs and require a prompt surgical repair as soon as diagnostic is know. Direct suture of the aorta is possible without prosthetic graft. Perioperative mortality is very low and long-term prognosis is good. PMID- 1925358 TI - [Surgical treatment of aneurysms of the thoraco-abdominal aorta]. AB - Surgical treatment of thoraco-abdominal aortic aneurysms, E. Kieffer. Thoracoabdominal aneurysms have a high potential for rupture, that justifies extensive indications for surgery. Mortality and spinal cord injury rates depend on age and general condition of the patient as well as extent and etiology of the aneurysm and the possibility of preoperative visualization of spinal cord arteries. PMID- 1925359 TI - [Treatment of HIV infection with zidovudine. The good use of AZT]. PMID- 1925360 TI - [Hepatic alveolar echinococcosis]. AB - Alveolar echinococcosis (AE) is an uncommon parasitic disease that is caused by the intrahepatic growth of Echinococcus multilocularis larvae. Eastern France is endemic for AE. A wild cycle allows the parasite to subsist in nature. The adult worm develops in the small intestine of foxes. The eggs of the taenia are dispersed on the ground by the foxes' stools. Rodents are infested by eating contaminated vegetables and larvae develop in the liver. Humans, accidental intermediate hosts, become infested due to either eating contaminated wild fruits, or by touching foxes or dogs. The human lesions of AE are often compared to a liver cancer which progress very slowly, causing necrosis and fibrosis. Complications invariably occurred during the follow-up. The most frequent are biliary complications, bleeding related to portal hypertension or Budd Chiari syndrome. During the last years, important progress has been made in many fields concerning AE, particularly in the immunology, epidemiology and therapy of this disease. The sole efficient treatment is partial hepatectomy. Recently, liver transplantation have been successfully performed for incurable AE. PMID- 1925362 TI - [Aneurysm in the year XII (1804). Anatomical Society of Paris]. PMID- 1925361 TI - [Mechanisms of pulmonary fibrosis]. AB - Lung fibrosis is characterized by the accumulation of extracellular matrix and mesenchymal cells leading a progressive loss of respiratory functional units. The accumulation of mesenchymal cells results from their migration and local replication. These cellular events are dependent upon the local presence of cytokines with chemotactic and/or mitogenic activity. The sequence of events leading the lung fibrosis is thought to result from a stereotyped response: after an initial injury, an inflammatory reaction develops and controls tissue repair through local production of cytokines. The permanency of these processes results in the development of fibrosis. PMID- 1925363 TI - [Macrocytic anemia in adults. Physiopathology]. PMID- 1925365 TI - [Unconjugated hyperbilirubinemia. Diagnostic orientation]. PMID- 1925364 TI - [Local, regional and general anesthesia. Evaluation of risk factors]. PMID- 1925366 TI - [Persistent fever. Diagnostic orientation]. PMID- 1925367 TI - [Natural or synthetic antibacterial antibiotics. Principles and rules of administration]. PMID- 1925368 TI - [Therapeutic trial. Principles of interpretation]. PMID- 1925369 TI - [Secondary amenorrhea. Diagnostic orientation]. PMID- 1925371 TI - [Etiology of multiple sclerosis]. AB - The risk of developing Multiple Sclerosis is under the combined influence of environmental and endogenous factors, as shown by epidemiological and genetic studies. Immunological abnormalities are a salient feature of the disease but their myelinotoxic effect is still to be demonstrated. The pathogenesis of the disease remains unknown. The auto-immune theory as well as the infectious theory are arguable but they may, also, be both valid. Multiple sclerosis could be a post-infectious auto-immune disease, "final common way" of common childhood infections. Anyway, no infectious agent is demonstrable inside the central nervous system at the overt disease stage. PMID- 1925370 TI - [Epidemiology of multiple sclerosis]. AB - Multiple sclerosis is unevenly distributed throughout the world. Its prevalence depends on latitude: it decreases in each hemisphere from pole to equator. France is situated in a high prevalence zone, with 40 cases for 100,000 inhabitants. The prevalence of multiple sclerosis is modulated by risk factors unrelated to latitude; genetic susceptibility factors (HLA, Gm), as well as environmental, occupational, nutritional and infectious (notably viral) factors have been identified, but no conclusion can be drawn concerning their role in the aetiology and pathogenesis of the disease. Among the hypotheses that could put an end to this deadlock, the heterogeneity of multiple sclerosis must seriously be considered, and it might serve as a basis for further epidemiological studies benefiting from recent technological developments such as molecular genetics and magnetic resonance imaging. PMID- 1925372 TI - [Multiple sclerosis. From lesion to symptoms]. AB - Clinical manifestations of multiple sclerosis cannot be exactly correlated with lesions identified by brain imaging, electrophysiology or even anatomy. It is generally accepted that a continuous conduction is possible within some demyelinated fibers, and a conduction block may occur in the CNS white matter without demyelinization. These data explain the possible occurrence of brief, repetitive deficits besides the classical relapses. Among the latter, at least some are not correlated with demyelinization. The knowledge of these mechanisms suggest the possibility of therapy to restore the conduction without a direct action on the demyelinating process. PMID- 1925373 TI - [Diagnosis of multiple sclerosis]. AB - Multiple sclerosis definition is anatomical. Its symptomatology is not specific and 4 main criteria are necessary in order to obtain a diagnosis of certitude or of presumption: 1) dissemination of signs and symptoms in space and time; 2) respect of age; 3) the symptomatology must be the expression of lesions affecting mainly the white matter; 4) elimination of other possible diagnosis. CSF examination, evoked potential and NMR study may help to the diagnosis, but no abnormality is specific of multiple sclerosis. PMID- 1925374 TI - [Benign forms of multiple sclerosis]. AB - It is still difficult, in 1991, to evaluate precisely the position occupied by benign forms of multiple sclerosis (MS) in the natural history of the disease. The reality hidden behind the adjective "benign" varies from one author to another, and the estimated frequency of these forms is not the same when one refers to epidemiological studies on whole populations or to clinical studies in major hospitals. There is, however, no doubt that benign MS does exist, since about 10% of MS patients will suffer, throughout the whole duration of the disease (over 30 years), from no more than moderate disablement with few repercussions on their social and professional life. These are patients in who MS began when they were 20 to 30 years' old and evolved by episodes rather than progressively and whose main symptoms are optic neuritis and sensory disorders without pyramidal or cerebellar deficit. Nevertheless, these cases are not easy to recognize a priori: there is no paraclinical examination that can predict a benign course in the long term, and an MS which has long been benign may become worse at any moment. PMID- 1925375 TI - [New imaging methods by nuclear magnetic resonance in multiple sclerosis]. AB - Magnetic resonance imaging (MRI) has rapidly attained a major position among the examinations used in the diagnostic approach of multiple sclerosis because it is highly sensitive in demonstrating lesions. However, these lesional images may have several meanings, and there is the problem of distinguishing between oedema, which is said to reflect recent lesions, and gliosis which is thought to betray old lesions. The intrinsic MRI parameters studied (i.e. relaxation times) are unable to make this distinction, whereas it is provided by paramagnetic contrast media such as gadolinium. There is no correlation between the changes observed at MRI and the severity of the disease. Another problem is the accuracy of lesion localization, since visualization is predominantly macroscopic. This raises several questions about the demonstration of correlations between clinical signs and site of the lesion(s). At the moment, several teams of neuroradiologists are trying to find the most reliable method to determine the size of the lesion. The possible prognostic value of this size and its changes as time goes by are other parameters to be considered once the basic diagnosis has been made. PMID- 1925376 TI - [Intellect and mood disorders in multiple sclerosis]. AB - Recent studies showed that mild or moderate cognitive deficits and affective disturbances are frequent in patients with multiple sclerosis and can be found early in the course of the disease. Cognitive deficits are related to brain lesions but not clearly to functional disability. Affective disturbances are partly determined by the presence of brain involvement, but also by an emotional reaction to the disorder. Psychological disorders must be taken in account for a better management of the patients and their family. PMID- 1925377 TI - [Hirudin. A new and promising anticoagulant from leech]. PMID- 1925378 TI - [By how much can the duration of dialysis sessions be shortened? To shorten can be harmful]. PMID- 1925379 TI - [Markers of autoimmune liver diseases]. PMID- 1925380 TI - [Rett syndrome. A well defined but mysterious encephalopathy]. AB - The Rett syndrome is characterized by a progressive development of loss of intellectual functions and of motricity, including abnormal stereotypic hand movements and reduction of the motor skill. This syndrome is exclusively observed in girls. Its typical evolution is characterized by a normal initial development (until 6 to 18 months after birth) followed by a progressive installation of the clinical signs in 4 steps. There is currently no biological marker for the Rett syndrome and therefore the diagnosis is only based on clinical criteria. The most common erroneous diagnosis is infantile autism. In this review, the current status of clinical, genetic and pathogenetic knowledge of the Rett syndrome is presented. PMID- 1925381 TI - [The discovery by Paul-Louis Simond of role of the flea in the transmission of plague]. PMID- 1925382 TI - [Chernobyl five years later]. PMID- 1925383 TI - [Sarcoptic scabies. Epidemiology, diagnosis, principle of the treatment]. PMID- 1925384 TI - [Circulatory arrest in adults. Diagnostic orientation and emergency treatment]. PMID- 1925385 TI - [Acute pulmonary edema. Physiopathology, diagnosis, principles of treatment]. PMID- 1925386 TI - [Hemorrhage after delivery. Diagnosis, principles of the treatment]. PMID- 1925387 TI - [Anemia. Diagnostic orientation]. PMID- 1925388 TI - [Acute infectious diarrhea. Diagnostic orientation and emergency treatment]. PMID- 1925389 TI - [Mumps. Epidemiology, diagnosis, development, prevention]. PMID- 1925390 TI - [Scoliosis in children and adolescents. Screening, surveillance]. PMID- 1925391 TI - [Vaccinations. Immunological and microbiologic basis, indications, contraindications, accidents, efficacy]. PMID- 1925392 TI - [True or false arterial hypertension in Paget's disease. Role of mediacalcose]. PMID- 1925393 TI - [Tibial valgization osteotomy in gonarthrosis with or without chondrocalcinosis. Results after 5 years]. AB - The authors compare the results of valgisation tibial osteotomies in osteoarthrosis of the knee (146 cases) and osteoarthrosis of the knee with chondrocalcinosis (94 cases). The two groups were identical in terms of age, but differed by sex ratio (female predominance in CCA) and the initial radiological stage (more advanced forms in the CCA group). Results differed after the second year and reached significantly different values at 5 years (73% in knee osteoarthrosis as against 34% good clinical results in chondrocalcinosis). Study of two groups of patients paired for age, sex, weight and radiological stage showed that results at 5 years were significantly less good in the CCA group. These results are discussed and compared with those in the 1990 literature. PMID- 1925394 TI - [Phosphate diabetes and Paget's disease: 2 cases]. AB - The authors report 2 cases of Paget's disease associated with phosphate diabetes. The hypothesis of the secretion of a phosphaturic substance by Paget's bone cells is discussed. PMID- 1925395 TI - [Myeloma and epidural invasiveness. Clinical and therapeutic aspects (a study of 22 cases)]. AB - The authors have retrospectively studied 22 cases of spinal cord compression among 184 patients having multiple myeloma or plasmocytoma. Neurological signs were the initial symptoms of the malignant plasmocytosis in 32% of the cases. Seven patients had paraplegia, 13 paraparesia and three had no motor involvement. A laminectomy was performed in half of the cases (with or without local radiotherapy and/or chemotherapy); the 11 other patients were treated by radiotherapy and/or chemotherapy alone. Sixteen patients (72%) improved, 10 in the laminectomy group and six in the other. The improvement seemed to be better after the laminectomy (and/or radiotherapy or chemotherapy) but to a lesser extend if the patients were paraplegic, in case of sudden onset and of compression at the thoracic level. The median of survival was 30 months. They emphasize the utility of magnetic resonance imaging for the diagnosis of epidural involvement before the occurrence of objective neurological complications. PMID- 1925396 TI - [Levels of IgA rheumatoid factors in seropositive rheumatoid polyarthritis. Absence of correlation with disease activity or pejorative course]. AB - Rheumatoid factors of the IgA isotype directed to human IgG Fc fragment were assayed, using an Elisa test, in the serum of 30 patients with seropositive rheumatoid arthritis and in the synovial fluid of 9 of them. A high incidence was found in the serum (90%) and synovial fluids (77%). Clinical, radiological and biological parameters of each patients were recorded at the time of the assay, and two years later. There was no statistically significant association between IgA rheumatoid factors levels and other parameters, nor with a pejorative evolution. However, a significant negative correlation was observed between IgA rheumatoid factors levels and the duration of the disease, suggesting that IgA rheumatoid factors are predominantly produced at the earliest stages of rheumatoid arthritis. PMID- 1925398 TI - [Dual-photon absorptiometry of the calcaneum in osteoporosis. Preliminary results]. AB - Anteroposterior views of the lumbar spine are commonly used for the measurement of bone mineral density (BMD) by diphoton absorptiometry (DPA). Values in lumbar vertebral BMD can be increased by the existence of a compression fracture, osteoarthrosis, scoliosis or aortic calcifications. Evaluation of bone loss at a peripheral site, such as the calcaneum (essentially trabecular site), could compensate for the principal causes of error associated with vertebral measurement. Calcaneal BMD in 195 control women was used to establish reference values closely correlated with lumbar BMD (p less than 0.001). The same study was undertaken in osteoporotic women. Preliminary results based upon 38 cases are reported here. Measurement of BMD of the calcaneum was correlated with vertebral trabecular bone density measured by double energy CT scan, indicating that this peripheral site offers a good reflection of what is happening at vertebral trabecular level. In contrast, calcaneal BMD was not correlated with spinal BMD, except if patients with osteoarthrosis and/or scoliosis were eliminated. Measurement of the BMD of the calcaneum by DPA is thus a simple, rapid and reproducible method for evaluation of a trabecular bone site which could be complementary to the measurement of lumbar BMD when the latter is falsified by artefacts. PMID- 1925397 TI - [Evans' syndrome caused by D-penicillamine in rheumatoid arthritis. Value of the corticoids-danazol combination]. AB - The authors report the development of thrombocytopenia purpura in one patient with seropositive and erosive rheumatoid arthritis treated successfully for 11 months with D-penicillamine. Anti-platelet-bound antibodies were present, but also: anti-erythrocyte antibodies with hemolytic anemia (then defining Evans's syndrome): higher level of antinuclear antibodies; intermittent neutropenia. The responsibility of D-penicillamine is discussed, but thrombocytopenia purpura evolved for itself. Glucocorticoids alone, intravenous immunoglobulin, vincristine did not induced remission, which at least occurred under the association danazol-glucocorticoids, without toxicity, especially on the liver function. PMID- 1925399 TI - [Ankylosing spondylarthritis and partial cauda equina syndrome. Apropos of 4 cases and review of the literature]. AB - Four new cases of ankylosing spondylitis complicated by a cauda equina syndrome are reported. Similarly to the previous descriptions, the patients present with long-standing and severe spondylitis at the time when neurological symptoms, mainly radicular pain, develop. Computed tomography of the lumbar spine demonstrates in all cases typical laminar erosions and posterior arachnoid diverticula. Up to now, magnetic resonance imaging has rarely been performed in this particular pathology, though it is helpful in determining the anatomical relations and the nature of the lesions. Based on the previous publications, our study aims at describing the clinical and pathogenic aspects of the disease and defining the most useful diagnostic investigations and treatment choices. Therapeutic possibilities are often limited because of a late diagnosis. Better knowledge of this rare complication could lead to earlier recognition and more efficient therapy. PMID- 1925400 TI - [(Iatrogenic?) intraventricular thrombus and Behcet's disease]. PMID- 1925401 TI - [Hip osteonecrosis with rapid chondrolysis and algodystrophy]. PMID- 1925402 TI - [Spondylarthropathy of late onset? RS3PE? An overlap form?]. PMID- 1925403 TI - [Apropos of two cases of infectious oligoarthritis in rheumatoid arthritis]. PMID- 1925404 TI - [Cheirarthritis and Dupuytren's disease associated with diabetes mellitus]. PMID- 1925405 TI - [Complex fractures of the middle third of the face and the anterior region of the base of the skull. Implementation of diagnosis and treatment]. PMID- 1925406 TI - Gastric potential difference measurements. The gastric mucosal integrity and function studied with a new method for measurement of the electric potential difference across the stomach wall. AB - PD--the electric potential difference across the gastric mucosa--is a variable used to describe the gastric mucosal integrity and function. A new, reliable, and easily applied method for gastric PD measurements corrected for the disturbing liquid junction potentials between gastric juice and the PD measuring probe is presented. PD is measured with the gastric lumen negative, and a numeric reduction in PD is used as an expression of an injured mucosal condition. A reduced gastric PD is found along with a reduced gastric mucosal blood flow after intravenous indomethacin in anesthetized dogs. Increasing the FFA/albumin ratios in mini-pigs causes vasoconstriction and PD reduction. Short hypoxia and selective gastric ischemia cause a reversible PD reduction and no morphologic changes in anesthetized dogs, but ischemia for 1 h causes more permanent changes in PD, pH, and morphology. This damage can be reduced by allopurinol pretreatment, possibly due to the inhibition of oxygen-derived free radical formation. Gastric PD and pH were measured in volunteers and duodenal ulcer patients during Stroop's color word conflict test, in which mental stress causes sympathetic activation. A PD reduction and a pH increase were found along with stress induction, thereby indicating an influence of mental stress on stomach mucosal function. It is concluded that gastric PD measurement may be useful in ulcer pathogenetic research, and a sufficient gastric mucosal blood flow is stressed as being important for the mucosal defense. PMID- 1925407 TI - Lecture for the Nobel Prize for physiology or medicine 1972: Structural studies of immunoglobulins. 1972. PMID- 1925408 TI - Phorbol myristate acetate corrects impaired NK function of old mice. AB - Previous studies indicated that natural killer (NK) activity in mice declined with age. In this report, we investigated the basis for the decreased activity of NK cells in older mice. Our results demonstrated that phorbol myristate acetate (PMA)--an activator of protein kinase C (PKC)--corrects the impaired NK function of older animals. The per cent increase of NK activity post treatment with PMA is 226-261% at effector:target (E:T) ratio = 100:1 compared with control untreated cells. The effect of PMA was shown to be dose dependent. A maximum increase in NK activity was achieved at approximately 10-15 nM PMA. Treatment with PMA does not result in increased binding of NK cells to YAC-1 targets as demonstrated by single-cell assay. In addition, treatment of young NK cells with 1-(5 isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride (H-7), a very potent PKC inhibitor, significantly suppressed NK activity (65% of control). Therefore, we conclude that the age-related decline in murine NK activity may reside in the early signalling events leading to triggering of PKC. PMID- 1925409 TI - Immunoglobulin-mediated prevention of autoimmune diabetes in the non-obese diabetic (NOD) mouse. AB - We investigated whether the development of spontaneous T-cell-mediated type I diabetes in NOD mice is influenced by B cells and immunoglobulin (Ig). During the first 4 weeks of life, B-cell development was suppressed by repeated administration of rabbit anti-mouse IgM (RaIgM), while controls received polyclonal rabbit Ig (NRIg). A reduction in the incidence of diabetes, as well as in development of insulitis, was observed after either of these treatments. However, the effect on insulitis was more pronounced in mice treated with RaIgM compared with those treated with NRIg. Furthermore, while the optimal effect of NRIg was obtained after a single injection at birth, the additional effect of RaIgM on development of insulitis was observed only after continued treatment for the first 4 weeks of life. Taken together these data suggest a possible role of Ig/B cells in the development of autoimmunity in the NOD mouse. The additional effect observed after continued suppression of the neonatal B-cell development suggests that this population may contribute significantly to the establishment of an auto-aggressive lymphocyte repertoire in the NOD mouse. PMID- 1925410 TI - Hidden rheumatoid factor and Wa idiotype expression in juvenile rheumatoid arthritis. AB - The major rheumatoid factor cross-reactive idiotype, which was defined by prototypic monoclonal IgM rheumatoid factors from Waldenstrom's macroglobulinaemia patient Wa, is present on 60% of all monoclonal IgM RF paraproteins. One-third of patients with juvenile rheumatoid arthritis (JRA), who are seronegative for classic IgM rheumatoid factor (RF), express the Wa idiotype in high titre in their sera. To determine if the Wa idiotype is present on hidden rheumatoid factors in JRA patient sera, we studied hidden RF expression by both ELISA and haemolytic assay techniques. The majority of JRA sera with increased concentrations of the Wa idiotype did not have increased RF activity nor hidden RF activity. In some JRA patients, the Wa idiotype may be expressed on a parallel set of immunoglobulin molecules, related to RFs, but lacking the ability to bind to IgG. PMID- 1925411 TI - Cell cycle-dependent expression of CD4 antigen in a monocytoid cell line. AB - The CD4 molecule has several biological functions, physiologically as a receptor for major histocompatibility complex class II molecules on antigen-presenting cells, and pathologically as a receptor for human immunodeficiency virus (HIV) by its binding to the HIV envelope glycoprotein gp 120. The frequency of CD4+ cells has been shown to correlate positively with both susceptibility and cytopathogenic effect by HIV. To determine if CD4 expression varied during the cell cycle, a CD4-expressing monocytoid cell line, U 937 clone 16, was synchronized with regard to cell growth. The CD4 antigen was analysed with regard to expression, density and rate of reappearance after treatment with trypsin, during the different phases of the cell cycle. The CD4 reappearance rate was found to be maximal during the S phase. This was followed by an increased expression and density in the late S/G2 phase. Thus a cell cycle-dependent expression of CD4 molecules on the cell surface was observed. PMID- 1925412 TI - Non-immune binding of human protein Fv to immunoglobulins from various mammalian and non-mammalian species. AB - Reactivity of the secretory protein Fv with immunoglobulins (Ig) from various species of vertebrates was investigated. Binding was observed throughout all taxonomic classes: mammalian, avian, reptilian, amphibian and fish. Contrasting with this wide spectrum, no significant binding was found with most mammalian ungulates, such as horse (Perissodactyl), cow, sheep and goat (Artiodactyls). Nevertheless, disruption of the hydrogen bonds of Ig allowed these non-reactive molecules to bind. Such a conserved reactivity during evolution, and our previous data on the effect of the cleavage of the intra-chain disulphide bonds, suggest that protein Fv recognizes a discontinuous framework structure involving both the FR1 and FR3 regions in the variable domain of the heavy chain of Ig. PMID- 1925413 TI - Evaluation of knee joint cartilages and menisci in patients with chronic inflammatory joint diseases. A prospective arthroscopic study before, six and twelve months after open synovectomy. AB - Destruction of joint cartilage is an important feature in chronic inflammatory joint diseases. This article considers the areas of the cartilages of the knee joint prone to destructive changes, pannus growth and marginal erosions, and the changes of pattern after open synovectomy. Twenty-eight patients with chronic inflammatory joint disease which gave indication for synovectomy of the knee joint had arthroscopy immediately before, 6 and 12 months after open synovectomy. A method of grading the changes of the cartilage, pannus growth, menisci and marginal erosions is described. There was an increase in cartilage pathology 12 months after synovectomy (p less than 0.001), particularly on the weight bearing areas of the femur and on the tibial condyles. No significant deterioration in areas with pathology at the time of synovectomy was found in the follow up. Pannus growth was particularly located to areas 2 and 4 on the femoral condyles. We conclude that cartilage destruction after synovectomy is more likely to be a result of osteoarthrosis than arthritic changes. PMID- 1925414 TI - Development of a solid phase enzyme immunoassay for the detection of anti-Ro autoantibodies. AB - An enzyme immunoassay was developed to detect anti-Ro(SS-A) autoantibodies. Both Ro-antigen components (52 and 60 kD) were purified from a pig spleen extract, using fast protein liquid chromatography (FPLC). Anti-La, anti-RNP, anti-DNA and anti-Sm antibodies do not react to the purified antigen. There was a strong correlation between anti-Ro activity in EIA and the titers in counter immunoelectrophoresis (rs = 0.893). Anti-Ro antibodies were found in 54 (69.2%) of 78 SLE sera by the developed EIA. PMID- 1925415 TI - Quantitative radio-isotope scanning in ankylosing spondylitis: a clinical, laboratory and computerised tomographic study. AB - Quantitative sacroiliac and lumbar spine radio-isotope (Tc-99m MDP) scans were performed in 42 patients with ankylosing spondylitis, and repeated 12 months later in 25. Clinical and laboratory assessments as well as computerised tomographic (CT) scans of the sacroiliac joints (SIJ) and lateral lumbar spine x rays, were performed. Bone (using the L3/4 area of the lumbar spine, sacrum, SIJ's and knee) to soft tissue (ST) ratios all correlated strongly with each other. Patients with high SIJ:ST ratios had significantly greater low-back stiffness (p less than 0.05). Change in serum IgA levels correlated negatively with change in bone: ST ratios. There was no relationship between bone: ST ratios and any other clinical or laboratory variables. The change in SIJ:ST ratios correlated positively with change in CT erosion score (p less than 0.05) and negatively with change in CT ankylosis score (p less than 0.05). PMID- 1925416 TI - Improved cost-effectiveness ratio with a patient self-adjusted naproxen dosing regimen in osteoarthritis treatment. AB - A standard fixed dosing regimen (S) and a variable dosing regimen (VD) of naproxen for patients with knee and hip osteoarthritis were compared in a multicentre, open, controlled, parallel 8-week trial. The daily dose of naproxen (Naprosyn) in the S-group was 500-1000 mg, in VD maximum daily dose was 1000 mg. The number of patients entering the study was 396 (286 females). Mean (SD) age was 67 (10) and 67 (11) years in the S- and VD-groups respectively. The number of patients available for efficacy analyses, including the withdrawals, was 356. Efficacy measures included pain on movement, night pain, morning stiffness, a functional index and patient's and doctor's overall assessments. Similar improvement was seen in both groups. The number of patients withdrawn due to adverse reactions in S and VD was 35 and 23 respectively (p less than 0.05). Group differences in drug consumption were highly significant (p less than 0.01) with a 20-30% lower consumption in the VD-group. Thus, similar efficacy and possibly better tolerance was obtained with a lower drug consumption by a variable dosing regimen compared to a fixed regimen. PMID- 1925418 TI - Oral S-adenosylmethionine in primary fibromyalgia. Double-blind clinical evaluation. AB - S-adenosylmethionine is a relatively new anti-inflammatory drug with analgesic and anti-depressant effects. Efficacy of 800 mg orally administered s adenosylmethionine daily versus placebo for six weeks was investigated in 44 patients with primary fibromyalgia in double-blind settings. Tender point score, isokinetic muscle strength, disease activity, subjective symptoms (visual analog scale), mood parameters and side effects were evaluated. Improvements were seen for clinical disease activity (P = 0.04), pain experienced during the last week (P = 0.002), fatigue (P = 0.02), morning stiffness (P = 0.03) and mood evaluated by Face Scale (P = 0.006) in the actively treated group compared to placebo. The tender point score, isokinetic muscle strength, mood evaluated by Beck Depression Inventory and side effects did not differ in the two treatment groups. S adenosylmethionine has some beneficial effects on primary fibromyalgia and could be an important option in the treatment hereof. PMID- 1925419 TI - Is there variation in chondrocyte function? PMID- 1925420 TI - Causes and prevention. PMID- 1925417 TI - Zopiclone in the treatment of sleep abnormalities in fibromyalgia. AB - The clinical and polysomnographical effects of zopiclone were evaluated in 41 patients with fibromyalgia in a double blind controlled study. A significant improvement was observed regarding tiredness during the day and subjective sleep complaints, but no effects on pain or stiffness were observed. The sleep structure remained unchanged during treatment. Zopiclone seems to be of value in treating the sleep complaints in patients with fibromyalgia. PMID- 1925421 TI - Genetic epidemiology utilizing the adoption method: studies of obesity and of premature death in adults. AB - Genetic epidemiology gives no priority to genes or environment in the search of disease causation. However, a major problem in this field is the disentangling of the effects of environment and genes. The study of subjects separated very early in life from their biologic parents and adopted by unrelated parents provide a strong tool for estimation of genetic and familial environmental influences. The degree to which the trait or disease frequency of the adoptees is similar to that seen among the biologic relatives is an indication of the strength of the genetic influence. Similarity to the adoptive relatives suggests influences of the family environment shared between them. Adoption studies of adult obesity show that it is genes, and not the family environment, that is responsible for the familial aggregation of obesity. A study of the mortality of adult adoptees and their biologic and adoptive parents indicates a genetic influence on the risk of premature death from all causes, from natural causes, infections, and cardio- and cerebrovascular conditions, and suggests familial environmental influences on death from the vascular causes and from cancer. PMID- 1925422 TI - Winter weather conditions and myocardial infarctions. AB - The daily number of cases of myocardial infarctions admitted to a hospital in middle Sweden over three winter seasons 1984-87 was correlated to the weather conditions on a day-to-day basis. The study encompassed 634 days and all cases younger than 70 years, living within the catchment area, in all 382 subjects. Information on temperature, wind force, precipitation and atmospheric pressure was obtained from the Swedish Institute of Meteorology and Hydrology. A low number of myocardial infarctions was seen on Saturdays and Sundays with a mild wind chill factor and on days with moderate snowfall and high atmospheric pressure. A high number was observed for workdays, especially Mondays, as day of diagnosis. Heterogeneity of the study population and a misclassification of the time relationships between dates of diagnosis and weather changes may have caused an underestimation of the impact of weather conditions. However, weather conditions do not seem to be a major triggering factor of myocardial infarctions in Sweden. PMID- 1925423 TI - Does spousal physical abuse affect the outcome of pregnancy? AB - The relationship between living in a physical abusive relationship and adverse outcome of pregnancy was examined using a structured interview including an obstetrical history. Sixty-six women living in a physically abusive relationship, and 114 women randomly selected and not presently living in such a relationship were interviewed. The women reported 312 completed pregnancies. Five of these were twin pregnancies and one was a stillbirth without information on birth weight. Of the 306 pregnancies included in the analysis, violence had occurred in 40. The mean birth weight of births reported by women exposed to violence during pregnancy was 229 g less than the equivalent figure in non-exposed pregnancies. Adjustment for education, primiparity, and history of addiction reduced the difference in mean birth weight to 175 g. PMID- 1925424 TI - Different contraceptive practices: use of contraceptives in Finland and other Nordic countries in the 1970s and 1980s. AB - Contraceptive practices, especially oral contraceptive and intrauterine device use, were studied in four Nordic countries by recalculating published and unpublished data from previous surveys and statistics and by collecting new data from Finland. The sales of oral contraceptives were presented in defined daily doses, and the percentages of women using oral contraceptives were estimated from them. The percentages of intrauterine device users were calculated taking into account the number of intrauterine devices sold each year and the continuation of use from previous years. The results of the surveys were reanalysed. We found clear differences in contraceptive practices. Oral contraceptive use was most prevalent in Sweden and Denmark, and, especially at the end of the 1970s, Finnish intrauterine device use was very high. In the 1980s the differences dimished somewhat. These disparities in culturally and economically similar countries indicate that further research is needed to evaluate the factors influencing contraceptive practices. PMID- 1925425 TI - Contraceptive use in random samples of Greenlandic and Danish women--changes from 1986 to 1988. AB - As part of a study of risk factors for cervical cancer, the possible change was assessed in the use of condoms after AIDS campaigns. In 1986, samples of 800 women aged 20-39 years were drawn at random from Nuuk/Godthab (Greenland) and Nykobing Falster (Denmark). A total of 586 and 661 women were interviewed in Greenland and Denmark, respectively. In 1988, new random samples of 150 women were drawn from the same areas. Totally, 129 Greenlandic and 126 Danish women were included in the study. From 1986 to 1988 the prevalence of ever having used condoms increased significantly among Greenlandic women aged 20-29, whereas no statistically significant changes were observed in Denmark. This pattern was independent of the lifetime number of sexual partners. Neither in Greenland nor in Denmark did the mean lifetime number of sexual partners change from 1986 to 1988. PMID- 1925426 TI - Prevalence of smoking and oral contraception in a sample of Danish young women. AB - A representative sample of 286 Danish females aged 16-20 years were interviewed during the period April 1984--February 1985. The response rate was 75%. Both use of oral contraception (OC) and smoking were common; 46.6% used OC, 34.2% smoked and 19.6% combined smoking and OC. The prevalence of smoking was significantly higher (42.0%) among OC-users than among non-users (27.2%). The combination of smoking and OC was especially prevalent among young women with sexual debut before 16 years (36.8%). The association between smoking and the use of OC was significant both when tested unstratified (p less than 0.05) and stratified by age at sexual debut (p less than 0.01). Smoking was also associated with early debut of intercourse (p less than 0.001). It has been reported that the combination of these two factors in adult women increase the risk for cardiovascular mortality. However, the health consequences later in life of combining smoking and OC at young ages have not been illuminated in the literature. These findings indicate the necessity for prospective studies of young women. PMID- 1925427 TI - What causes stress for mothers of children with MBD? AB - Adapting the paradigm developed by Richard Lazarus, parenting stress and coping were studied among mothers of 6-9-year-old children (n = 42) with different symptoms of Minimal Brain Dysfunction (MBD) (hyperkinesis, perceptual or motor deficits, learning disabilities or speech disorders) and among mothers of non disabled children (n = 42) matched for age, sex, social status of the family and marital status. Mothers of children with MBD were found to experience more parenting difficulties and more negative cognitive appraisals of their stakes in parenting than their matched controls. The mothers of children with hyperkinesis and perceptual or motor deficits considered their mastery lower and experienced less positive affects than their matched controls. The mothers of children with speech disorders experienced less positive affects than their matched controls. Mothers of children with both few and several symptoms experienced more parenting difficulties in the child domain than their matched controls. Mothers of children with several symptoms considered their mastery lower and experienced less positive affects; mothers of children with few symptoms appraised their stakes in parenting more negatively than their matched controls. No significant differences were found between mothers of children with MBD with few and several symptoms. PMID- 1925428 TI - Strategies implemented but goals not attained. Some comments on an evaluation of the Swedish mental health services. AB - Is the development of Swedish psychiatry a success or not? Available information allows different answers to this question. Valid knowledge would demand psychiatric health service research on a much larger scale and with considerably higher ambitions than hitherto. Strong arguments can be raised about the need for such research to avoid that psychiatry will remain a medical wasteland in which confused policy makers will allocate less interest and money than ever. PMID- 1925429 TI - Self-assessed quality of life and metabolic control in persons with insulin dependent diabetes mellitus (IDDM). AB - The aim of the study was to analyse the association between satisfaction with life and glycosylated haemoglobulin (HbA1). A quality of life questionnaire was administered to 247 persons with IDDM at a Diabetic Clinic in Bergen, Norway. The material was divided into two groups depending on their level of HbA1; HbA1 greater than 0.09 was labelled poorly regulated and a level of HbA1 less than or equal to 0.09 was labelled well regulated. The groups were compared with regard to different life domains and well-being scales. The statistical analysis showed that the well-regulated group had significantly higher average scores considering the somatic and activity/behavioural life domain ratings, the latter being only significantly different among people with higher education. The well-regulated group had lower average scores in the psychological and social life domain ratings, but these differences were not statistically significant. Among the well being scales we found a statistically significant difference between poor and well-regulated persons only regarding sociability and loneliness. Well-regulated persons felt on average less sociable and more lonely than poorly-regulated persons. PMID- 1925430 TI - The effect of a weight reduction program on cardiovascular risk factors among overweight hypertensives in primary health care. AB - The aim of the study was to test the effect of a nonpharmacological weight reduction program on cardiovascular risk factors among overweight hypertensives in a primary health care setting. Forty-nine overweight hypertensive patients completed the 12-month program. The patients were randomly allocated into either intervention or control groups. The examinations included interviews by a nutritionist, pertinent laboratory tests, and a medical examination. The intervention involved an individually planned energy-restricted diet of 1000-1500 kcal per day, weekly discussions, and various leaflets on diet modification and on increase of physical activity. The mean body weight was reduced by 5 kg in the intervention group, but remained unchanged in the control group. The intervention group reduced their fat intake by 14 g/day while the control group increased it by 9 g/day on the average. In the intervention group, the total serum cholesterol decreased, HDL-cholesterol increased and triglycerides decreased significantly. The systolic blood pressure fell by 8 mm Hg and 15 mm Hg in the intervention and control groups, respectively. The diastolic blood pressure fell on average by 11 mm Hg in both groups. The results demonstrate the comprehensive weight reduction program to be effective in the control of cardiovascular risk factors. PMID- 1925431 TI - The quality of retrospective questions about occupational history--a comparison between survey and census data. AB - The main purpose of the present study was to assess the quality of information about occupational history obtained via retrospective interview questions. This assessment is achieved by linking interview data from the Swedish survey of Living Conditions (ULF) with occupational information about the same individuals obtained from a number of censuses. This has been done for the census years 1960, 1970, 1975 and 1980. In both ULF and the census, occupations have been classified according to the Nordic Occupational Classification (NYK). Both data sources contain errors. There are also differences in definitions and measurement procedures. Still, the survey question on occupational history gives results of good quality in terms of agreement with census data. This is especially the case for coarse levels of the classification scheme (NYK 1-digit level). The agreement is somewhat lower for the comparisons farthest back in time. PMID- 1925432 TI - Risks, benefits and economic consequences of total hip arthroplasty in an aged population. AB - An attempt was made to evaluate risks, benefits and costs of total hip replacement in patients over 80 years. Forty consecutive replacements in 37 patients were analysed and the results were compared to a younger population (36 patients) concerning complications and duration of hospitalization. The elderly group was reexamined two years postoperatively to assess the outcome. There was a significantly prolonged stay in hospital/long-term care for the octogenarians, 31.1 days compared to 13.6 for the younger group, as well as an increased risk for complications. Eleven patients had 18 different complications (11/40; 27.5%) in contrast to 2 complications in 2 patients (2/36; 5.6%) in the younger population. Quality of life was increased in terms of pain relief and there was moderate improvement in function. For the elderly, the community expenses for welfare services were not found to be reduced after the intervention. It is concluded that the observed improvement of quality of life has to be balanced against the increased risks and costs for this group. PMID- 1925433 TI - Occupational health problems among nurses. AB - Nurses are an integral component of the health care delivery system. In discharging their duties, nurses encounter a variety of occupational health problems which may be categorized into biological hazards, chemical hazards, physical hazards, and psychosocial hazards. A review of some examples of each of these four types of hazards is presented in this article. Particular attention has been devoted to hepatitis B, acquired immunodeficiency syndrome, tuberculosis, cytotoxic drugs, anesthetic agents, needlestick injury, back pain, and stress. PMID- 1925434 TI - Renal cell cancer and occupational exposure to chemical agents. AB - A case-referent study of occupational risk indicators of renal cell adenocarcinoma was conducted. Each incident case in Finland in 1977-1978 was matched with two population referents. Lifelong job histories were collected and translated into indicators of industry, occupation, and occupational exposures. The analyses of 338 sets of cases and referents revealed elevated risks for a history of employment in white-collar occupations; the printing industry; the chemical industry; the manufacturing of metal products; mail, telephone, and telegraph services; and iron and metalware work. A decreased risk was observed for male farmers. An elevated risk and an exposure-response relationship were found for gasoline exposure. The excess risk was highest at a latency period of approximately 30 years. The findings support the hypothesis that exposure to some constituent(s) of gasoline increases the incidence of renal adenocarcinoma in humans. Suggestions of elevated risks appeared for exposures to inorganic lead, cadmium, and nonchlorinated solvents. PMID- 1925435 TI - Occupation and gastric cancer in Spain. AB - The association between occupational exposure and stomach cancer was investigated in a multicenter case-referent study conducted in Spain on 354 histologically confirmed cases and 354 hospital referents, matched by age, gender, and residence. An increased risk of gastric cancer was found for coal mining workers [odds ratio (OR) 11.8], but the number of workers was small, and therefore the 95% confidence interval (95% CI) was wide (95% CI 1.36-103). An increased risk was observed for wood and furniture workers (OR 1.76), construction workers (OR 1.68), and glass and ceramic workers (OR 2.18), but none of these risks were statistically significant. According to an occupation-exposure linkage system an increased risk was found for occupations associated with exposure to silica and mineral dust (OR 1.80, 95% CI 0.90-3.59). All of the OR estimates were adjusted for the confounding factors socioprofessional status and dietary habits. The possibility of a causal association between stomach cancer and coal and mineral dust is supported by the results. PMID- 1925437 TI - Manganese exposure in steel smelters a health hazard to the nervous system. AB - In a study of the effects of low-level exposure to manganese (0.19-1.39 mg/m3 for 1-45 years) 30 men (aged 20-64 years) from two steel smelting works and 60 unexposed referents (aged 22-65 years) were examined with the use of a general health inquiry, electroencephalography, event-related auditory evoked potentials, brain-stem auditory evoked potentials, diadochokinesometry, simple and complex reaction time, finger tapping, digit span, mental arithmetic, vocabulary, a coding task, manual dexterity, symptoms, and mood scales, the diagnostic interview scheme, a dynamic rating scale for neurasthenic syndrome, and a comprehensive psychopathological rating scale. No group differences were found in the electroencephalography or the psychiatric examinations. However, there were increased frequencies of some symptoms, the diadochokinesis was slower, the P-300 latency and reaction time were increased, and finger-tapping and digit-span performance were impaired in the exposed group. These effects were interpreted as early (subclinical) signs of disturbances of the same type as parkinsonism. PMID- 1925436 TI - Occupation and cancer of the oral cavity or oropharynx in Turin, Italy. AB - In a population-based case-referent study, the occupational experience of 86 men with oral or oropharyngeal cancer and 373 referents was analyzed with respect to employment in 41 occupations and 40 industries, as well as to exposure to 16 chemicals, as estimated via a job-exposure matrix. Among the occupations and industries at higher risk were machinery operator (odds ratio [OR] 2.0; 95% confidence interval [95% CI] 1.0-4.0), plumber (OR 5.0, 95% CI 1.2-21.5), building industry (OR 2.5; 95% CI 1.3-4.5), textile industry (OR 2.5; 95% CI 0.6 4.6), and electricity production (OR 2.8; 95% CI 0.7-12.1). All the OR estimates were adjusted for age, education, area of birth, tobacco smoking, and alcohol consumption. An association between formaldehyde exposure and oral cancer was suggested (OR for any exposure 1.6, 95% CI 0.9-2.8; OR for probable or definite exposure 1.8, 95% CI 0.6-5.5). No other chemical included in the matrix showed any risk pattern. The evidence of an association between formaldehyde exposure and oral or oropharyngeal cancer is strengthened by the results of this study. PMID- 1925438 TI - Effects of occupational exposure to mercury vapor on lymphocyte micronuclei. AB - For 26 chloralkali workers exposed to inorganic mercury and 26 age-matched, occupationally unexposed referents, the frequency and size distribution of micronuclei were determined in peripheral lymphocytes stimulated with either phytohemagglutinin or pokeweed mitogen. For the exposed workers the mean concentrations of mercury in urine, plasma, and erythrocytes were 16 nmol/mmol of creatinine, 48 nmol/l, and 78 nmol/l, respectively, and their mean exposure time was 10 years. Neither the frequency nor the size of micronuclei was significantly different in the two groups; nor were there any correlations to current mercury levels. However, in the exposed group, and with phytohemagglutinin as the mitogen, a statistically significant correlation between previous exposure to mercury (cumulative exposure or number of blood mercury peaks) and the frequency of micronuclei was found. This association was also present when the effects of age and smoking were allowed for, and it may indicate an accumulation of cytogenetic effects in T-lymphocytes. PMID- 1925439 TI - Respiratory health of workers exposed to swine confinement buildings only or to both swine confinement buildings and dairy barns. AB - Swine building workers (N = 488) and nonfarming neighborhood referents (N = 216) were enrolled in this study. There was a slight but significant increase in the prevalence of chronic bronchitis (17.49 versus 11.57%) and more evidence of airflow obstruction (forced expiratory volume in 1 s/forced vital capacity 0.75 versus 0.78) among the swine workers when they were compared with the referents. The subjects who spent more than 3 h/d in the swine buildings had a higher prevalence of chronic bronchitis (21.94 versus 13.25%) and airflow obstruction (forced expiratory volume in 1 s/forced vital capacity 0.75 versus 0.76) than those with shorter daily contact. Swine building only workers had no precipitins to antigens found in their environment and no clinical evidence of extrinsic allergic alveolitis. The number of years on the farm, dual exposure with dairy cattle, positive skin prick tests, type of piggery, and type of feeding did not add to the respiratory health impact of swine buildings. PMID- 1925440 TI - Histamine and endotoxin contamination of hay and respirable hay dust. AB - Three distinct samples collected from a barn in which an outbreak of respiratory problems occurred were examined for possible etiologic agents. No causal relationship could be established from the results of this study; however histamine concentrations as high as 0.5 ng/mg for bulk hay (in the absence of measurable creatinine levels) along with 6138.3 endotoxin units/mg of hay were present in the samples. Both endotoxin and histamine could be recovered from respirable hay dust. The authenticity of the histamine found in the hay was evaluated with high-performance liquid chromatography and radioimmunoassay. Histamine release caused by hay extracts was evaluated with the use of leukocytes from the farmer and a referent. Histamine is known to modulate the immune system, but the role of occupational or environmental exposure to histamine in respiratory disease is unknown. PMID- 1925441 TI - Highlights of the 1990 Leesburg, Virginia, International Workshop on Retrospective Exposure Assessment for Occupational Epidemiology Studies. PMID- 1925443 TI - [Ozone, ventilatory function and bronchial reactivity]. AB - Forty adult hospital workers were followed prospectively in 1989 by monthly assessment of the lung function and bronchial responsiveness to methacholine in a rural region in Switzerland. No correlation was demonstrated between these values and the concentrations of tropospheric ozone. Nevertheless, this is not incompatible with previous studies showing impairment of ventilatory function in subjects exposed to ozone, for several reasons: ozone levels in 1989 were low, the indoor concentrations were lower than outdoors and the volunteers performed little or no physical activity. PMID- 1925442 TI - [The biochemical modulation of 5-fluorouracil by leucovorin]. AB - 5-fluorouracil (5-FU) is the most effective drug in the treatment of advanced colorectal carcinoma and has definite activity in a variety of other solid tumors. However, remissions occur in only about 20% of the patients and usually are of short duration. Biochemical modulation is a way of enhancing the efficacy of 5-FU by manipulation of intracellular metabolic pathways. Leucovorin (LV) prolongs the inhibition of the key enzyme, thymidylate synthetase, by stabilizing the ternary complex with activated 5-FU, thus leading to "thymidine-less" death. Phase II trials showed promising response rates in colorectal, gastric, and breast cancer. This translated into prolonged survival and into an increased therapeutic index in some phase III studies comparing the combination 5-FU/LV with 5-FU monotherapy in colorectal cancer. The present article focuses on the pharmacological background of the therapy with 5-FU/LV, summarizes the clinical data and gives a short overview on other ways of increasing the therapeutic index of 5-FU. PMID- 1925444 TI - [Bodybuilding: hypokalemia and hypophosphatemia]. AB - In preparing for competitive body building, body builders--in addition to continuous and hard muscle training--engage in stringent dietetic manipulations: the first few months of hypercaloric nutrition, rich in proteins, are devoted to the build-up of muscle mass. A second phase of reduced caloric intake is designed reduce subcutaneous fat, while, during the last week of preparations, extreme carbohydrate intake aims at loading muscles with glycogen. Simultaneously, sodium and water restriction results in extracellular and therefore subcutaneous volume deficit and better "definition" of muscle contours and structure. In the course of these dietetic manipulations a young body builder develops hypokalemia, hypophosphatemia, rhabdomyolysis and flaccid tetraparesis. The disturbances are pathophysiologically predictable. PMID- 1925445 TI - [Pulmonary venous occlusive disease. Case report and literature review]. AB - We present the case of a 64-year-old female patient who died of pulmonary veno occlusive disease. The patient had suffered for several months from increasing dyspnea and right heart failure. Chest x-ray showed signs of pulmonary hypertension as well as Kerley A- and B-lines and pre-edema and a moderately enlarged heart. The diagnosis of pulmonary veno-occlusive disease was confirmed by open lung biopsy. We compare our case with the other cases of pulmonary veno occlusive disease (PVOD) published in the literature. PMID- 1925446 TI - [Laboratory diagnosis in HIV infection]. AB - The laboratory diagnosis of an HIV infection is mainly based on the detection of antibodies. Many reliable tests are commercially available. Although they have excellent characteristics (sensitivity and specificity above 99%), their positive predictive value is low in populations with a very low prevalence of HIV infections. Therefore, reactive screening tests must be validated by a confirmatory test in order to reduce the probability of false positive results to an acceptably low level, i.e. below 1%. The detection of HIV by cell culture, antigen detection or genome detection is less standardized and, as a single test, less sensitive than the antibody tests. It is useful as an additional investigation in cases where the results of antibody tests are equivocal. PMID- 1925447 TI - [Antiretroviral therapy in Switzerland 1991]. AB - Zidovudine (azidothymidine, Retrovir) and ddI (di-deoxy-inosine, Videx) interfere with the multiplication of HIV by incorporation into nascent DNA chains and interruption of the further linking of nucleotides. Zidovudine lowers early mortality in patients with Aids and pneumocystis carinii pneumonia. However, much of the effectiveness of zidovudine is lost later on; the average prolongation of life in treated patients is estimated to be about 1 year. About two thirds of patients with Aids can be treated with zidovudine; in the others, the drug is ineffective or contraindicated. Frequent blood counts are necessary to monitor myelotoxicity, even at relatively low doses of 500 mg/day. In contrast, zidovudine is well tolerated by asymptomatic patients with 200 to 500 CD4 lymphocytes/mm3, in whom it diminishes the incidence of Aids from about 7 to 3% during the first year of treatment, with less than 2% severe anemia or leukopenia. For patients who do not tolerate zidovudine, ddI is an alternative. It is not myelotoxic but can cause neuritis and pancreatitis, especially at doses in excess of 10 mg/kg/day. Although its antiviral effect is excellent both in vitro and in vivo, there is still a lack of firm data on its clinical value, such as the decrease in opportunistic infections and increase in survival. PMID- 1925449 TI - [Justice and injustice in AIDS: problems in HIV-testing and physician's duty to secrecy]. AB - The present Swiss legal position on the following two questions is described and discussed. First, under what circumstances can a physician test a patient for HIV antibodies (or, more generally, use diagnostic methods) without the patient's express consent? Second, in what cases can he inform others of the patient's HIV status (or, more generally, breach medical confidentiality) without the patient's agreement? Informed consent of the person involved is the most important justification; as a rule the consent must be signified specifically and expressly both for tests and for the breach of confidentiality. Tacit consent may be assumed only in special circumstances; a request for a checkup, for example, in no way includes (for the present at any rate) tacit consent to HIV testing. Another possible justifying ground is protection of third parties. However, testing (especially secret tests) for the protection of medical and nursing staff is, in the present stage of development, neither suitable nor necessary for such protection and hence is legally unjustifiable. Nor, except in cases of admissible emergency assistance, is confidential notification of sexual partners legally admissible. Finally, there may be a justifying legal basis and overriding public interest in exceptional cases, e.g. where, in certain circumstances, the authorities order an open, compulsory HIV test in an individual case or unlinked tests for epidemiological purposes, or, if need be, for a physician's notification of the public health authorities in cases of desperado behaviour by HIV positive patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1925448 TI - [Ambulatory therapy and prevention of the most frequent HIV-associated opportunistic infections]. AB - Earlier diagnosis and improved therapies for the opportunistic infections have led to improved quality of life as well as survival time of patients with advanced HIV-related immunodeficiency. Most of the therapies can be administered on an outpatient basis. Outpatient treatment further contributes to improving the quality of life of the patients. Presentation, clinical aspects, treatment and prophylaxis of the five most frequent opportunistic infections in HIV-infected patients with advanced immunodeficiency in our outpatient clinic (oral and esophageal candidiasis, pneumocystis carinii pneumonia, herpes zoster, herpes simplex virus infection and cerebral toxoplasmosis) are discussed with respect to the practical implications. PMID- 1925451 TI - [Bacterial meningitis: pathophysiology and therapy 1991]. AB - The new concepts of pathogenesis and pathophysiology of purulent meningitis are discussed and evaluated in logical sequence. Possible therapeutic down-modulation of the initial burst of inflammatory responses, especially with steroids (dexamethasone), is critically analyzed. Prompt and adequate antibiotic therapy remains the essential measure in the management of patients with bacterial meningitis. The individual aspects of antimicrobial therapy are described and specific recommendations are made. PMID- 1925450 TI - [Selection of seropositive persons for AIDS as practiced by group insurance agents (disease and professional caution) in Switzerland]. AB - Rejection, exclusion and discriminating attitudes may disturb an AIDS prophylactic approach, which is based on individual responsibility. Fear, apprehension and mistrust induce dissimulation, evasion and refusal. In Switzerland, the selective policy of some group insurances, which offer necessary covering for employment, forms a prejudicial element of social splitting for seropositive people. The practice of HIV-tests for exclusion purpose promotes a tendency to secrecy, which is unfavourable to the social and medical control of the epidemic, especially because medical secret relatively to insurances is insufficient. This situation alarms the Swiss Aids Foundation which has put forward several motions and began speaking with the most important representative unions of Swiss insurers. PMID- 1925452 TI - [Surgical treatment of hepatic hydatidosis]. AB - Between January 1981 and December 1990, 41 patients were operated on for hepatic hydatid disease, representing 18% of the overall surgery for liver disease performed in our institution during the same period of time. The mean age of the patients was 39.5 years (range 17-71 years), 24 were females and 17 males. The most common clinical sign was abdominal pain (59%) with 3 patients jaundiced at the time of admission. 2 patients suffered from acute rightsided pneumonia, one of them with a very important productive cough due to bronchial perforation of the hydatid cyst of the liver. One patient was admitted due to anaphylactic shock with collapse. For 14 patients (34%) the discovery of the disease was casual, either by clinical hepatomegaly or by X-ray investigations performed for other reasons. We performed 18 pericystectomies, 4 subtotal pericystectomies and 16 liver resections. Only 3 patients were treated by partial cystectomy with removal of the prominent part of the cyst. Several other surgical procedures were performed concomitantly, including 2 pulmonary lobectomies, 1 cystojejunostomy, and pericystectomies for other hepatic or extrahepatic localizations of hydatid cysts. Rupture of the cyst into the bile duct was diagnosed in 13 patients. One patient presented with a peritoneal rupture of the cyst and 2 patients had a fistula through the diaphragm into the pleural cavity. Our postoperative morbidity is acceptable (10 patients, 25%). A bilioma and a biliary leak were successfully treated by percutaneous drainage, a postoperative hemorrhage required surgical treatment, four patients experienced pulmonary complications and the three others minor wound abscesses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1925453 TI - [The therapeutic effects of the calcium blocker verapamil in chronic diarrhea. Preliminary communication]. AB - The results of an open clinical trial carried out between 1985 and 1989, studying the effect of calcium antagonists, particularly verapamil, on chronic diarrhea of different etiologies, are presented. 44 patients out of 46 (95.65%) experienced total remission of symptoms. 3 cases of colitis improved from stage III to stage I (Bockus), thus avoiding already planned surgery. The usefulness of verapamil in the control and prophylaxis of diarrhea either after gastroenteric surgery or induced by travel or Crohn's disease should be pointed out. 2 non-responders suffered from drug induced diarrhea (lithium, carbamazepine). In spite of the large doses given (up to 720 mg), the side effects were negligible and in no case did the treatment have to be interrupted. In some cases the treatment lasted from some weeks to several months, and in cases of diarrhea after gastroenteric surgery or of hyperkinetic colon even for three to four years. The known action of calcium antagonists on smooth muscle and intestinal absorption probably accounts for the therapeutic efficacy of these drugs in diarrhea. PMID- 1925455 TI - [Interactions of cytostatic agents with other drugs]. AB - With the degree of polypharmacy currently practiced in the field of oncology, there are undoubtedly many drug interactions. In the present study the influence of "non-cytotoxic" drugs on anticancer drugs is discussed, but not the reverse. Not only is the augmentation (reversal of multidrug resistance) or the reduction of antitumor properties of cytotoxic drugs observed, but also cytostatic activities of "non-cytotoxic" drugs themselves. Examples are calmodulin inhibitors such as phenothiazines and tricyclic antidepressants. Interactions may also increase side effects of cytostatic drugs or even neutralize the antitumoral activity. To ensure that interactions are not overlooked, all medicaments being administered should be listed. It is, however, not feasible yet to determine serum concentrations of all the drugs given to the patient. The antitumor activity of supportive care could be evaluated in randomized studies (e.g. cytostatic drugs +/- antidepressants). PMID- 1925454 TI - [Spontaneous dissection and stenosis of the vertebral artery]. AB - The case of a 21-year-old female patient with neck pain and brain stem symptomatology after appendectomy is reported. Duplex sonographic findings were compatible with right vertebral artery dissection and occlusion of the vessel. Angiography confirmed the diagnosis. The patient recovered within weeks and was free of symptoms 6 months after the acute episode. Dissection of the vertebral artery can occur with or without minor trauma. Associations with fibromuscular dysplasia, arterial hypertension and the use of oral contraceptives have been reported. As in our own patient, dissection can appear without any vessel pathology or risk situation. The most dangerous complication of the disease is rupture of the adventitia with subarachnoid hemorrhage. Without this complication, prognosis of vertebral artery dissection is favourable with complete recovery within weeks. Clinical findings, diagnostic procedure and therapy are discussed. PMID- 1925457 TI - [Silicone endoprosthesis in the treatment of tracheobronchial stenosis. Report of the first 12 patients treated with this method]. AB - Inoperable tracheobronchial stenoses are most often due to malignant disease. Apart from systemic therapy, various local treatment modalities such as laser resection, cryotherapy and endobronchial radiation therapy have been designed to maintain airway patency. Recently, various models of tracheobronchial stents (or endoprostheses) have been designed to maintain airway patency. They prevent recurring endobronchial tumor growth or progressive extrinsic compression of dilated airways. Silicone stents are highly suitable for this purpose. We treated 12 patients (11 males, 1 female, median age 68,5 years) suffering from bronchial carcinoma (6), esophageal carcinoma (4), metastatic colon carcinoma (1) and metastatic osteosarcoma (1). One stent per patient was inserted at the following sites: 6 in the right main bronchus, 4 in the trachea, 1 in the left main bronchus and 1 tracheobronchial left. We observed 2 complications: one obstruction of a bronchial stent by secretions which could be managed by fiberbronchoscopy and one short fire to a bronchial stent on repeat laser therapy. Rapid and lasting relief of dyspnea was observed in all patients. Our initial experience with a median follow-up of 2 months confirmed the easy insertion technique, the excellent effect and tolerance as well as the simple postoperative care of these silicone stents. Their use immediately after relief of a tracheobronchial obstruction by local means can be recommended. PMID- 1925456 TI - [Effects of jogging on mental well-being and seasonal mood variations: a randomized study with healthy women and men]. AB - The long-term effect of jogging on mental well-being and seasonal mood variation was examined in a randomized, controlled intervention study with healthy, middle aged, sedentary, non-smoking, white collar subjects. 17 women and 39 men were allocated to jog 2 h/week for 4 months, whereas 16 women and 22 men served as controls. After 4 months, there was a partial cross-over with the controls now taking up jogging. After 8 study months, all 38 subjects of the second jogging intervention as well as 10 women and 30 men of the first 4-month jogging period were re-examined for the second time. All participants in the second re examination were mailed a survey questionnaire one year after beginning of the study (response rate 83%). Despite varying adherence for the exercise regimen, the 4-month "net effects" (i.e. effect in exercise group minus effect in control group) showed a significant improvement in physical fitness (endurance capacity, resting heart rate) in men, but not in women. Among the mood scales assessed, "anger" showed a marginally significant effect in men (relative decrease; p = 0.05) and "calmness" a significant effect in women (relative increase; p = 0.02); after exclusion of 4 non-compliers from analysis in women, also "vigor" (relative increase; p = 0.03) and "depressiveness" (relative decrease; p = 0.02) were significantly improved after jogging. In women, the number of kilometers run was significantly correlated with an improvement in mental well-being (Pearson's r = 0.32 with change in 4 "positive" mood scales and r = 0.57 with change in 4 "negative" mood scales). Changes in endurance capacity were not significantly related to changes in mental well-being. However, in both women and men these mental effects of jogging were superposed by clear seasonal variations in mood, i.e. by a deterioration of mental well-being during the winter months and by a slow "remission" during summer. Taking jogging-induced and seasonal effects on mood together, the magnitude of the 1-year variability in mental well-being was somewhat attenuated in those study groups jogging, with this "buffering" effect reaching statistical significance in women (p = 0.050). We conclude from this training study with normal subjects that regular jogging of approximately 10 to 15 km/week may help to diminish the deterioration of mood observed during winter months (e.g. increase in depressiveness), especially in women. Hereby, a training induced increase in endurance capacity is apparently not a prerequisite for this long-term mental effect of jogging. PMID- 1925458 TI - [Narcolepsy--undiagnosed for 23 years]. AB - A 43-year-old man had suffered from recurrent episodes of unconsciousness over twenty-three years. No definite diagnosis was forthcoming from numerous hospital stays and diagnostic work-ups, including three cardiac catheterizations which demonstrated severe aortic stenosis. Valve replacement, carried out on the assumption of aortic stenosis-induced syncopes, confirmed the aortic stenosis but the episodes of unconsciousness recurred and were now attributed to psychosomatic cardiovascular disturbances and hypochondria. Narcolepsy was diagnosed only during the 22nd hospital stay - not by further technical diagnostic procedures but by careful study of the history. PMID- 1925459 TI - [Fatal voluntary poisoning by parenteral paraquat]. AB - Paraquat is a potent herbicide, very toxic in the concentrated liquid form as supplied to farmers. Suicidal poisoning represents a serious emergency with a known high mortality rate. Suicidal poisoning following the parenteral route has been rarely reported. A 16-year-old girl was admitted to our emergency unit after subcutaneous injection of gramoxone 20% (about 400 mg of paraquat). Despite immediate surgical excision and revision, and subsequent antioxidant treatment with N-acetylcysteine (400 mg/kg/day during 48 hours), she died 17 days later from refractory hypoxemia following pulmonary fibrosis. From this observation and from the literature, it appears that an effective treatment does not depend on changes in the toxicokinetics of the herbicide (hemoperfusion, antidotes, drugs). PMID- 1925460 TI - [Stenosis of the terminal portal vein branch in acute myeloid leukemia]. AB - The endstage in a patient suffering from acute myeloid leukemia secondary to myelodysplastic syndrome was characterized by bleedings, anemia, pain in the upper abdomen and ascites. At autopsy the radicles of the portal veins were occluded by leukemic infiltrates and fibrosis. These lesions block the perfusion of the liver presinusoidally and, together with the anemia (hypoalbuminemia), result in ascites resistant to all therapy. PMID- 1925461 TI - [Actinomycosis--clinical and therapeutic considerations based on 2 personal case reports]. AB - We report on two patients with actinomycosis. The first case was a 45-year-old cachectic man with extensive bilateral pulmonary infiltrates. The lesions remained unclear for 18 months and only open lung biopsy with microscopic and cultural evaluation led to the diagnosis of actinomycosis. In the second case, classic cervico-facial actinomycosis in a 69-year-old farmer is described. Diagnosis was established on the basis of microscopic findings of "sulphur granules" eroding the mandible. Furthermore, the clinical presentation, with an indurated swelling of the jaw and intraoral fistula formation, was typical. The patient had a severe combined aortic valve lesion and died after ventricular fibrillation during hospitalization. Diagnosis could not be confirmed by culture, probably due to antibiotic prophylaxis against endocarditis during tooth extraction on the first day of admission. Diagnostic difficulties and microbiologic aspects are discussed, with special focus on the rare species of Actinomyces meyeri which was cultured from biopsy specimens from the lung of the first patient. So far this species has been described in only 13 patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1925462 TI - [Sterilization of mentally retarded women]. AB - The sterilization of mentally retarded women raises gynecologic, psychiatric and legal questions. Gynecologic considerations include the experience of the reliability of reversible contraceptive methods with mentally retarded patients and questions concerning the type of operation. From the psychiatric point of view the prognoses of mentally retarded patients and the expected psychic coping with the operation are essential aspects in the indication for sterilization. Last but not least, the Swiss legal framework for sterilization must be considered. This aspect is illustrated on the basis of the results of a catamnestic analysis of 21 patients operated on between 1980 and 1987. PMID- 1925463 TI - [Continuous quinidine infusion and blood exchange transfusion in severe tropical malaria: a case report]. AB - We report on a serious case of malaria due to Plasmodium falciparum. Although the 46-year-old Swiss female had strictly followed the recommended prophylaxis with proguanil and chloroquine she was infected during a stay in Namibia which had lasted several month. The patient had poor prognostic signs such as encephalopathy (cerebral malaria), a parasitemia of 34% but only moderate renal impairment. Instead of the classical treatment with quinine, the patient was treated with a constant infusion of quinidine over 3 days which was combined with an exchange transfusion of approximately 2 liters on the first day of treatment. All clinical signs of the infection improved within less than 2 days as did the parasitemia. The patient was discharged after a hospital stay of 11 days. Quinidine as opposed to quinine may be more readily available, less toxic and more efficacious. Treatment with quinidine must carefully be monitored. Exchange blood transfusions may be an important additional therapeutic modality in severe plasmodium falciparum malaria. PMID- 1925464 TI - [Mycobacterium marinum granuloma in a fish fancier. Apropos of a case with sporotrichoid lesions]. AB - A 43-year-old fish fancier with fish tank granuloma presented with a sporotrichoid-like skin infection of the right arm with multiple papulo-nodular lesions along the lymphatic drainage. Acid fast bacilli were found in skin biopsy specimens and Mycobacterium marinum grew in cultures. The clinical and histopathological findings in M. marinum infection are reviewed and the differential diagnosis, laboratory findings with this atypical mycobacterium, and therapeutic modalities are discussed. Finally, the importance of an adequate and pertinent patient's history for a correct and timely diagnosis is stressed. PMID- 1925465 TI - [Cyst of the seminal vesicle with ipsilateral kidney agenesis]. AB - Unilateral cyst of the seminal vesicle, ipsilateral ectopic ureter and ipsilateral renal agenesis are the components of a rare congenital abnormality affecting the male urogenital tract. The clinical picture is characterized by a retrovesical cystic tumor which may be asymptomatic or cause nonspecific symptoms. Differential diagnosis includes cysts of the Mullerian duct, the urogenital sinus/ejaculatory duct, and the prostate. Pelvic ultrasonography is an appropriate method of investigating patients in whom this malformation is suspected, whereas more invasive radiologic procedures are indicated in selected cases only. Treatment for retrovesical cysts should be restricted to symptomatic patients. Conservative therapy may result in subjective improvement, but surgical exploration and excision of the abnormal organs is the only definitive treatment. PMID- 1925466 TI - [Benefits and side effects of preoperative autologous blood donation in 11 heart surgery patients]. AB - Patients scheduled for cardiac surgery are prone to adverse reactions during blood donation due to hemodynamic instability. 11 selected patients donated three units of red blood cell concentrates and three units of fresh frozen plasma (FFP) preoperatively in 11-day intervals under careful hemodynamic monitoring. 24 hours preoperatively autologous plasmapheresis (500 ml) was carried out in 10 patients at bedside. No complications were seen in any patients. The patients' mean hemoglobin concentrations were 142 +/- 11, 133 +/- 6, 128 +/- 7 and 126 +/- 7 g/l (mean +/- 1 SD) before each autologous blood donation and before the plasmapheresis respectively. No significant changes were noted in major hematological and chemical screening tests. Serum iron, iron-binding capacity and ferritin levels remained within the normal range. Due to additional perioperative blood saving methods, such as reinfusion of centrifuged oxygenator-blood (559 +/- 119 ml) and shed mediastinal blood (518 +/- 353 ml), only two patients needed additional transfusion of 1 homologous red cell unit each. On average 2.18 autologous red cell concentrates were retransfused per patient. PMID- 1925467 TI - [Prevalence of risk factors for osteoporosis and distribution of calciuria and hydroxyprolinuria in an elderly population of a general practice. Results of a survey among 32 practitioners of the Vaud and Fribourg districts]. AB - 169 postmenopausal women and 84 male patients aged over 59 years from the outpatient consultations of 32 general practitioners were examined. The most frequently encountered risk factors for osteoporosis were low physical activity (41% of women, 27% of men), low intake of dairy products (37%/21%), smoking (11%/22%), while the particularly relevant risk factors were more rare, such as corticotherapy (7%/9%) and early menopause (17%). The risk factors were not more frequent than in 550 persons of the same age screened among the Swiss general population in another study. The same group of persons also yielded reference values for urinary calcium and hydroxyproline in the fasting urine, which are both considered as markers of bone turnover and as potential tools for screening osteoporosis. The urinary values were independent of age, body mass index, calcium intake, and the duration of the postmenopausal period. They were different from those found in 38 patients with Paget's disease, 66 patients with malignant hypercalcemia and 25 with bone metastasis from breast cancer. Calcium and hydroxyproline excretion are expressed as a ratio of urinary creatinine. Percentiles 10 and 90 of urinary calcium are 0.058 and 0.363 mmol/mmol (male) and 0.062 and 0.523 mmol/mmol (women). Percentiles 10 and 90 for urinary hydroxyproline are 0.006 and 0.024 mmol/mmol (male) and 0.010 and 0.025 mmol/mmol (women). PMID- 1925468 TI - [Combined oral and endoscopic mepacrine therapy in therapy-resistant symptomatic giardiasis]. AB - A case of extremely refractory infection with Giardia lamblia is described. A 28 year-old male patient with a 7-year history of mushy diarrhea and epigastric pain was repeatedly treated orally and intravenously, without success, with metronidazole, tinidazole, ornidazole, and mepacrine. The rate of success for these drugs is generally more than 90%. Only therapy with mepacrine orally in combination with intraduodenal administration, was successful. Therapeutic failure of 5-nitroimidazole derivatives is described in relation to immune deficiency syndromes and IgA deficit. None of these defects were found in this case. PMID- 1925470 TI - [Beta-lactam/beta-lactamase inhibitor combinations for oral administration]. AB - Beta-lactamase inhibitors are compounds which are able to bind many beta lactamase and to inactivate them irreversibly ("suicide inactivators"). Their intrinsic antimicrobial activity is weak. However, in combination with aminopenicillins they exhibit marked synergism both in vitro and in vivo against many beta-lactamase producing bacterial strains. At the achievable serum and tissue concentrations after oral administration, various aminopenicillin/beta lactamase inhibitor combinations are active against many strains of beta lactamase producing Haemophilus influenzae, Moraxella catarrhalis, Bacteroides fragilis and staphylococci. At levels achievable in the urine, they are also active against many strains of Escherichia coli, Proteus spp. and Klebsiella spp. Clinically, they have been shown to be effective in the treatment of various human infections of the urinary tract, airways, skin, soft tissues, ear and sinuses. Mild gastrointestinal disturbances are the most commonly encountered side effects. Aminopenicillin/beta-lactamase inhibitor combinations may be a suitable therapeutic option in treating mild to moderately severe infections, i.e. in an outpatient setting. PMID- 1925469 TI - [Tumoral calcinosis with superinfection and sepsis]. AB - Tumoral calcinosis (TC) is a rare syndrome involving ectopic calcifications in the vicinity of the large joints. In about one third of patients the disorder is familial and is associated with hyperphosphatemia, elevation of 1,25-dihydroxy vitamin-D levels and peculiar dental lesion. TC is inherited in an autosomal recessive manner. In a normophosphatemic male patient with alcoholic cirrhosis of the liver, TC occurred first in the thoracic wall. Seven years after excision of the first lesion, a large tumor mass around the right hip developed. Infection of the calcified masses with Staph. aureus led to extensive abscess formation, septicemia and death at the age of 64. Clinical, dental and biochemical examination of the 7 descendants of the patient revealed no constitutional signs of the disease, thus identifying our patient as a sporadic case. Clinical and pathological findings in the patient are discussed and the literature is reviewed. PMID- 1925471 TI - [Therapy with aminoglycoside antibiotics: once daily (q.d.)?]. AB - Theoretical and experimental arguments favor administration of aminoglycosides once daily (q.d.). Results of clinical studies with a limited number of patients support these arguments. However, some practical and clinical questions remain unanswered. Therefore, q.d. infusion of aminoglycosides must still be considered experimental and must remain in the hands of infectious disease specialists until the results of ongoing clinical studies yield the ultimate proof that this novel dosing schedule is as efficacious and no more toxic than the conventional dosing regimens. PMID- 1925472 TI - [Antimycotic therapy in clinical practice]. AB - Mycoses commonly encountered in outpatients in Europe are usually limited to body surfaces and are no threat to the patient. Topical or systemic therapy with modern antimycotics is usually effective. Improved pharmacokinetic properties of newer azoles have shortened and simplified treatment of the mucosal forms of candidiasis for which a single dose of fluconazole (150 or 200 mg) or a short course with two doses of itraconazole (2 x 100 mg) are recommended. For patients with an uncorrectable predisposition to thrush, guidelines are provided for prophylaxis or self-initiated therapy. Whenever possible dermatophytoses should be treated topically to avoid long-term exposure to the new keratinotropic azoles and allylamines, for which insufficient long-term toxicological data are at present available. Ketoconazole should be avoided for these indications because of its potentially serious hepatotoxicity. For many indications requiring prolonged treatment griseofulvin remains the favoured systemic drug due to its extensive safety record. PMID- 1925473 TI - [Prosthesis infections: is ambulatory conservative therapy possible?]. AB - Infections associated with prosthetic devices involve an increased risk of persistence or relapse if the foreign body is not removed. Clinical and experimental observations indicate a lack of correlation between the minimal bactericidal concentration of a drug and its efficacy in device-related infections. Alternative in-vitro tests indicate that the efficacy of a drug experimental implant-associated infections depends on its activity on non-growing and adhering microorganisms. These data have been evaluated in a clinical pilot study. 12 patients with orthopedic device-related infections were treated with rifampin-containing regimens because this drug has excellent activity on adherent microorganisms. The success rate was 83% during a follow-up period of 2 years or until the removal of the device. Nevertheless, before considering conservative treatment of device-related infections, controlled clinical studies are needed which confirm the experimental results. PMID- 1925474 TI - [Trainees in internal medicine. Does the future general internist need scientific activities?]. PMID- 1925475 TI - [Aortocoronary bypass surgery in patients older than 70 years]. AB - From January 1981 to December 1990, 204 patients aged between 70 and 81 years underwent aortocoronary bypass surgery. Operative mortality (30-day mortality) was 6.8%. Actuarial survival rate at 1 and 5 years was 92% and 86% respectively. A higher incidence of postoperative complications was observed (arrhythmias in 19%, reoperation for bleeding in 5.4%, respiratory and neurological complications in 13% and 3% respectively, perioperative infarction in 4.4%). The mean follow-up was 25 months. Preoperatively most patients (71%) were in New York Heart Association (NYHA) functional class III and IV, and at the end of following-up in NYHA functional class I and II (95%) (p less than 0.001). A rapid rise in coronary artery surgery in the elderly is evident. It is associated with an increased but acceptable operative risk. Long-term results and postoperative improvement of functional status are very satisfactory. PMID- 1925476 TI - [Neurofibromatosis Type 1: genetic studies with DNA markers in 38 families]. AB - To establish preclinical DNA-diagnosis of neurofibromatosis type 1 (NF1) in familial cases we have investigated 38 families segregating for the disease. The families were tested with 6 polymorphic DNA markers from the chromosome region 17p11.1-q11.2. Two-thirds of the families were informative for flanking markers. An informative situation was achieved for 33 out of 40 individuals at risk (i.e. first degree relatives): 30 cases were diagnosed as noncarriers of the mutated gene, and three clinically normal individuals (including an adult and two children aged three and six respectively) were found to carry the risk haplotype. The remaining 7 persons at risk could not be typed unequivocally due to non informative markers or recombination events. In 5 families with healthy grandparents the origin of the mutation could be traced back to the grandfather's germ cells. Despite the recent cloning and initial characterization of parts of NF1 gene, studies using linked and eventually intragenic DNA markers will continue to be of great value for genetic counselling. Such analyses allow highly accurate preclinical and prenatal diagnosis in close relatives of familial cases. PMID- 1925477 TI - [Modifications in and prognostic value of the EEG in anoxic encephalopathy: 75 cases]. AB - The use of new cardiopulmonary resuscitation techniques has considerably increased the possibility of survival after cardiopulmonary arrest. It is of considerable interest to evaluate the extent of any anoxic brain damage. The EEG has proven very informative in the assessment of cerebral function in patients with anoxic encephalopathy. Its role is unchanged despite advanced imaging techniques. In 75 patients, the value of EEG recorded on the days after the onset of disturbances has been compared with the initial Glasgow coma scale (GCS) as a predictor of short-term prognosis. The EEG patterns were classified into 6 major grades and 12 sub-grades which were defined on the basis of the morphology of dominant activities, distribution and reactivity to external stimuli. A favorable outcome occurred with grade I to IIB associated with a GCS of 5 above. A bad prognosis was suggested by grades IVA to VC, particularly when epileptiform discharges were present, and the GCS was always below 5 in these patients. With new EEG grading scales in anoxic encephalopathies, the accuracy for predicting survival (or death) is now 90%. PMID- 1925479 TI - [Medical education--from captions in the examination book to the study-guidance evaluation of the learning process]. PMID- 1925478 TI - [Successful resection of a hypernephroma extending continuously into the right ventricle: utilization of extracorporeal circulation in general surgery]. AB - We report the case of a 53-year-old woman with renal cell carcinoma extending into the inferior vena cava and through the tricuspid valve into the right ventricle. Successful total removal was performed with the aid of cardiopulmonary bypass. The rarity of this case prompted a review of the literature in which only the involvement of right atrium in this type of tumor was found. Review of our own experience with extracorporal circulation in non-cardiac procedures demonstrates that an aggressive therapeutic approach, requiring operations of escalating magnitude and multidisciplinary surgical treatment, can salvage patients who otherwise might not be considered for operation. PMID- 1925480 TI - [The peripheral blood picture: a peephole gives insight into the struggle for survival of the body]. AB - The morphological features and fluctuation of cellular components derived from haemograms of a cat infected with toxoplasmosis provide information on the state and activity of important cell systems: the unspecific cellular defense by means of phagocytosis as well as the recruitment and functional stimulation of phagocytizing cells by cytokines and moreover the specific immune reaction, triggered by macrophages, phagocytizing, processing and presenting antigens to immune competent T-cells, inducing an immune response, which finally leads to the formation of antibody-producing plasma cells from B-cells. PMID- 1925481 TI - [Further cases of Capillaria hepatica in Switzerland]. PMID- 1925482 TI - [Epitheliogenesis imperfecta in lambs]. AB - In a herd of 23 ewes of the White Alp breed, a congenital epitheliogenesis imperfecta was observed in five twin-births. All lambs originated from the same father. Except in one case, only one of the twins was affected. Characteristic lesions were epidermal defects between the coronary groove and the carpal/tarsal joint, exungulation, and defects in the buccal mucosa (cheeks, palatum durum, tongue). After removal of the ram from breeding, no more abnormalities were observed. PMID- 1925483 TI - Maximal explosive power and aerobic exercise in humans. AB - The maximal explosive power (wmax), i.e. the mechanical power developed over short bursts (less than 5 s) of all-out cycling, or uphill running, in humans attains 12-17 W*kg-1 in non athletics subjects. Thus, in terms of O2 consumption wmax is about four times larger than the subjects VO2max. The peak instantaneous power during a vertical jump off both feet (w) in non athletic subjects is about 50-55 W kg-1 and attains 70-75 W*kg-1 in "power" athletes. Both wmax and w decrease when the all-out efforts is performed from a priming aerobic exercise: if the intensity of this last approaches VO2max, then wmax and w are reduced to about 75% the value attained from rest. Thus, in the course of high intensity efforts, an athlete can develop a still remarkable fraction of his maximal absolute power. The decrease mentioned above is proportional, and presumably causally related, to the decrease of the high energy phosphate concentration occurring in the muscle at the onset of the exercise, and maintained throughout the effort duration. PMID- 1925484 TI - [Doping according to the Italians]. PMID- 1925485 TI - [Reduction of physical endurance as an early symptom in Hodgkin lymphoma]. PMID- 1925486 TI - [Paralysis of the suprascapular nerve and tennis. Apropos of 3 groups of professional players]. AB - A recent surge of interest for tennis has given rise to an increased incidence of injuries to the N. suprascapularis. The early symptoms of this pathology are often missed, leading subsequently to a chronic condition, including an irreversible trauma to the nerve. Nevertheless, through the study of three groups of professional tournament players, we were able to show that the neurological injury is reversible if the diagnosis is established early on and if the hurting movement is avoided until full recovery. A backhand stroke done with both arms seems to have a protective effect against this pathology. PMID- 1925487 TI - [Subjective health and career status of former top athletes. A controlled 15-year follow-up study]. AB - 36 former Swiss elite athletes, all of them members of the National team in 1973, were re-examined in 1988 at an average age of 42 years, together with a control group of 23 normally active men. In 1988, maximum oxygen uptake (VO2max) was 68 +/- 5 ml/kg.min in the 18 still active runners, 55 +/- 8 ml/kg.min in the 9 inactive former runners, 45 +/- 6 ml/kg.min in bobsledders, and 44 +/- 6 ml/kg.min in controls. In 1988, the 27 runners had modest but significantly more frequent radiological signs of degenerative hip disease than non-runners, while no influence of long-term physical training on the radiological state of the ankle joint was found. In 1988, runners tended to report themselves healthier; subgroup analyses revealed 1) that this superior self-rated health was confined to those runners still active in 1988 (p less than 0.05) and that VO2max in 1988 was associated with subjective wellbeing (p less than 0.05), and 2) that body fat content was the strongest negative predictor of self-rated health (p = 0.001). 22% of former elite athletes indicated chronic, sports-related complaints but nevertheless rated their health as good as their athletic counterparts free of complaints. 53% of the elite athletes felt that the "benefits" of their own sports career outweighed its "costs", and in two of five of all athletes even "by far". This attitude was neither significantly influenced by the existence of chronic sports-related complaints nor by radiological signs of degenerative hip disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1925488 TI - Learning how bacteria swim could set new gears in motion. PMID- 1925489 TI - Industrial immunology. Antibodies may catalyze commercial chemistry. PMID- 1925490 TI - Graft without corruption. Antibody treatments could make transplanted organs acceptable. PMID- 1925491 TI - AIDS education may breed intolerance. PMID- 1925492 TI - Has AIDS peaked? Questions persist in modeling the deadly, atypical infection. PMID- 1925493 TI - Model mice. Transgenic animals and Alzheimer's research. PMID- 1925494 TI - [Effect of a mathematical model and number of measurements on accuracy in fetal weight estimation using ultrasound]. AB - The problem of foetal weight estimation has not been satisfactorily solved to date. We studied quantitatively the influence of the mathematical approach and the number of distance measurements of different parts of the foetal body, on the accuracy of prospective calculation of the actual foetal weight. Of 230 foetuses of known gestational age we measured via ultrasound 13 lengths of head, rump and extremities during the last three days before delivery. 22 types of formulas were analysed. To decide on the best mathematical way of calculation we recalculated all coefficients in all formulas for each study group. In this way each formula can yield best possible results for the presented group. Three formulas yield very good results--a logarithmic type using 7 measured distances, and 2 linear types of formulas using 10 and 11 measured distances. The standard deviations of the differences (calculated weight minus actual weight) range from 216 g to 219 g. The frequency of differences greater than +/- 15% of the calculated weight ranges between 3.0% and 4.3% of the cases. Miscalculations of more than 700 g (absolutely) have not been noted. In addition, five other formulas (logarithmic and linear types with 5 to 8 measurements) have yielded good results. Using 5 to 8 measurements, the logarithmic types of formulas are better than the linear ones. The mathematical types of formulas cannot achieve the improvements resulting from a greater number of measurements. PMID- 1925495 TI - [Transvaginal ultrasonic assessment of the endometrium in menopause]. AB - Early detection of endometrial cancer is hardly possible. In nearly 90% of all cases irregular vaginal bleeding is the first clinical sign of this disease. New ultrasound technique, small scanner probes and especially higher ultrasound frequencies rendered a better resolving power and higher quality medical imaging. Hence, now the examination of the organs in the female pelvis is very exact using vaginal sonography (VS). A clinical study was performed to examine the relevance of VS assessing changes and details of the endometrium. In particular, the sonographical criteria of early endometrial cancer should be defined. In 137 postmenopausal women VS was performed after irregular vaginal bleeding and prior to D&C. All findings were described concerning alteration in echogenicity and thickness of the endometrium. Only one case of 37 histological confirmed endometrial cancers among the study group was not detected by VS prior to curettage. Therefore 0.7% of the sonographical findings showed a false negative result and 6.6% were false positive in comparison to the histological outcome. VS seems to be a relatively reliable technique in assessing the endometrium. In conclusion VS could be a useful additional method to detect hyperplasia or malignant disorders of the endometrium. PMID- 1925496 TI - [Doppler ultrasound of the umbilical artery of the dystrophic child]. AB - In a group of 810 singleton pregnancies without malformations or chromosomal abnormalities blood flow velocity wave forms of the umbilical artery were recorded in the third trimester by means of a pulsed duplex Doppler system. We calculated the pulsatility index (PI). 133 newborn with a birthweight below the 10th centile were classified as small-for-gestational-age (SGA) (prevalence: 16%). The sensitivity of the test (elevated PI) for these neonates is 52% and the specificity 97%, the positive predictive value is 78% and the negative predictive value 91%. Therefore, Doppler Sonography of the umbilical artery is not an appropriate screening test to identify SGA babies prenatally. The results for jeopardized SGA babies (caesarean section because of pathological CTG traces, transfer to the neonatal intensive care unit) are much better. 31 out of 133 belonged to that group. For these foetuses, the sensitivity of the test is 94% and the negative predictive value 97%. Hence, Doppler Sonography of the umbilical artery allows very well to identify the endangered SGA foetuses on the one hand and to exclude foetal jeopardy with a normal PI on the other. PMID- 1925497 TI - [Continuous-wave Doppler ultrasound in the 2d and 3d trimester of pregnancy- normal values]. AB - Based on 427 patients with uneventful pregnancies and deliveries standard rates were established for the resistance index (RI) and the pulsatility index (PI) of the uterine, arcuate, and umbilical arteries. Percentiles, above all the 90th percentile, are more suitable localisation gauge than are standard deviations. In the observation period, i.e. from 18th to 42nd week of gestation, neither resistance nor pulsatility Index in the utero-placental compartment proved to be dependent on gestational age to any significant degree. By contrast, the umbilical artery showed a definite linear relation between the indices measured and gestational age. If the heart rates are in physiological ranges no clinically relevant effects of the heart rate on the measurement results were observed in either the maternal or the foetal compartment. PMID- 1925499 TI - [Vaginal ultrasound follow-up of suspicious smears of the cervix uteri]. AB - Using transvaginal sonography (TVS) it is possible to place the scanner probe very close to the organs of the female small pelvis. The near position allows the employment of a higher ultrasound frequency with a better resolving power and thus with more information about the examined structures. A clinical study was performed to investigate whether it is possible to gain some more information about alterations of the uterine cervix surface, after a suspicious cytology result, by applying TVS. A total 59 women with a pathological swab were examined, followed by conisation (using an operating knife) and a D & C. Histological examination showed that in 21 cases with sonographically not suspicious results, 10 cancers in situ and 1 early invasive squamous cell cancer could not be detected. The determined sensitivity of the method was 30.8%; the specificity was 59%. Concluding from the result TVS can be applied only with restriction concerning detection of beginning cancer of the uterine cervix. A statistical significance of vaginosonographical results compared with the suspicious smear results could not be established. PMID- 1925498 TI - [Doppler ultrasound in obstetrics--contribution to understanding reverse flow in the umbilical artery]. AB - "Reverse Flow" as a Doppler sonographic finding indicates the appearance of retrograde blood flow in the diastolic part of the cardiac cycle. It has so far not been observed in uncomplicated pregnancies and seems to be an indicator of severe deterioration of the foetal condition. Several pathophysiological hypotheses are discussed in this paper on the basis of own results and the findings of other investigators. PMID- 1925500 TI - [Vaginal sonographic imaging of the ovula Nabothi]. AB - Twenty patients, showing retention cysts in vaginosonographic examination, were included in our study. We differentiated between superficial and deep located Nabothian cysts. Fourteen cases showed primarily visible superficial cysts, the other six could only be detected vaginosonographically. The Nabothian cysts varied in size from 4 to 26 mm, the average diameter was 13 mm. Only four cases showed solitary Nabothian cysts, the other sixteen cases were multiple. The clinical significance of Nabothian cysts in the field of sterility diagnostics, especially the deep located retention cysts, cannot be assessed at present. PMID- 1925501 TI - [Color Doppler flow measurements in uterine cancers]. AB - Pulsed Doppler Flow Measurements in patients suffering from collum cancer using a coloured pulsed Doppler technique measurements of blood flow of the uterine artery were performed in a group of 35 patients suffering from an inoperable collum cancer (stage II and III according FIGO) and compared with a collective of 30 healthy women with normal anamnesis. The mean pulsatility index (PI) was significantly lower in the sick group (stage II 1.6 +/- 1.17, stage III 0.76 +/- 0.21) than in the healthy group (PI = 3.18 +/- 0.99) (p less than 0.01). In 14 subjects of the last group there was no significant difference in PI between the left and right uterine artery (left: PI 2.81 +/- 0.83), right: PI 2.78 +/- 0.76). PMID- 1925502 TI - [Comparative study of introital sonography and the urethrocystogram in women before and after surgery for stress incontinence]. AB - In a prospective study of sonographic and radiographic methodologies we compared morphologic bladder data in 30 patients before and after stress incontinence surgery. 18 women were subject to colposuspension according to Burch due to recurrent stress incontinence, 12 women underwent anterior colporrhaphy. Visualisation of bladder, urethra and beta-angle was adequate with both methods. The good visualisation of the anatomical and functional situation of the vesico urethral area is a major benefit of introital sonography. PMID- 1925504 TI - Hyperlipidaemia--what to do? PMID- 1925503 TI - [Ultrasound studies in early pregnancy]. AB - An ultrasound evaluation of the pregnancy in the first trimester is very helpful because no other method can better answer questions about the viability of the embryo, the true gestational age, the presence of an ectopic pregnancy and developmental anomalies at this early stage. Especially the introduction of vaginal sonography meant considerable progress in this area. Now there are normal growth curves available based on longitudinal measurements for the yolk sac, the amniotic and chorionic cavity and the crown-rump length. Significant deviations from these normal curves are suggestive of genetic anomalies of the developing child. Of these anomalies, detectable in the first trimester, especially the nuchal edema is associated with a high rate of chromosomal abnormalities. The fact that the gestational age can better be determined in the first trimester than in the later course of pregnancy is a strong argument for the introduction of routine ultrasound screening within the first twelve weeks of pregnancy. PMID- 1925505 TI - Pathology and clinical features of gastro-intestinal lymphoma in Saudi Arabia. AB - The histopathology and clinical presentation of 19 cases of primary gastrointestinal lymphoma is described. Our patients are similar to others in the Middle East but have a lower incidence of diarrhoea and malabsorption. All revealed a widespread chronic inflammatory background. Four patients with primary gastric lymphoma had endoscopic biopsies from the duodenum; these biopsies were completely free from tumour but showed a moderate to severe diffuse lymphoplasmacytic infiltrate. Electron microscopy shows that tumour cells penetrate basement membranes and invade the epithelium which becomes thin and attenuated. Substances which inhibit lymphocyte tropism might be useful in preventing intestinal ulceration. The MALT concept has been found useful in classification of the tumours. Two patients with unusual mesenteric node histology are described and it is thought that the appearances may indicate a substantial capacity for differentiation in the group of tumours. PMID- 1925506 TI - Metabolic control in diabetic subjects following myocardial infarction: difficulties in improving blood glucose levels by intravenous insulin infusion. AB - Optimal metabolic control during the first twelve hours after myocardial infarction may be associated with improved survival in diabetic subjects. A comparison of an intravenous insulin infusion regimen aimed at improving blood glucose levels (n = 35), with 'routine control' (n = 34) in the post infarction period has been carried out in diabetic subjects admitted to four Coronary Care Units over a two year period. However, glycaemic control was similar in both groups (intravenous infusion regimen, mean +/- SD capillary blood glucose 10.3 +/ 2.1 mmol/l, 'routine control' glucose 10.7 +/- 3.6 mmol/l). There were no differences in the rates of arrhythmias (31% v 32%), heart failure (46% v 47%) or mortality (17% v 18%). Mortality in diabetic subjects was lower than that quoted in previous studies but was higher than in non-diabetic subjects admitted to the Coronary Care Unit during the same period. Attempts to improve glycaemic control by means of intravenous insulin infusion were unsuccessful. PMID- 1925507 TI - Composition of seasonality of disease. AB - The composition of the seasonality of total death was ascertained. Vascular disease seasonality constitutes more than half. The remaining seasonality is influenced by respiratory disease. Surprisingly and of possible importance cancer mortality was not seasonal. Deaths from 'all other disease' and from 'injuries' is seasonal. Seasonality increases with age. In coronary and cerebrovascular disease death has a large seasonal fluctuation. On the other hand hospital admissions and survivors have a minor seasonal fluctuation--only cerebrovascular admissions reaching the chosen level of significance with a small seasonal amplitude. For vascular disease the ranking of seasonal fluctuation from greatest to least is--death outside hospital, total death, death inside hospital, admissions, survivors. It is death outside hospital presumably 'sudden' that imposes seasonality on coronary disease in general. For respiratory diseases not only death but hospital admissions and survivors have high amplitude seasonality with a much greater fluctuation than for death in vascular disease. PMID- 1925508 TI - Sudden death associated with aspiration of an antibiotic capsule. PMID- 1925509 TI - An unusual presentation of SLE. AB - SLE presenting initially with isolated pneumonitis is uncommon. We report a case of SLE which presented as an apparent infective lobar pneumonia without other definite evidence of SLE. Laboratory investigations eventually confirmed the diagnosis and clinical signs developed after the diagnosis was made. PMID- 1925510 TI - Brainstem vascular accidents and cranial arteritis. AB - Cranial Arteritis (Giant Cell Arteritis) is a clinical diagnosis supported by a raised erythrocyte sedimentation rate (ESR) and if required confirmed by a temporal artery biopsy. This case reports on an unusual presentation where a delay in the diagnosis resulted in visual impairment, illustrating the need for awareness of diagnosis in acute strokes in the elderly. PMID- 1925511 TI - The fetal valproate syndrome. PMID- 1925512 TI - Dr David Kinloch: Mediciner to His Majestie, James VI. AB - An account is given of Dr Kinloch whose portrait hangs in the library of Ninewells medical school. He led an adventurous life and served the Scottish and French Royal Families. He is remembered as a poet in whose Latin verse is given the first account of obstetric practice in Scotland. PMID- 1925513 TI - Pneumatosis cystoides intestinalis: a complication of colonoscopic polypectomy. AB - A 68-year old female underwent removal of a 3 cm transverse colon polyp, which contained adenocarcinoma, by means of endoscopic polypectomy. She tolerated the procedure well. Unfortunately, six hours later she returned to the hospital with vague abdominal complaints. Her clinical exam revealed mild abdominal tenderness, but was not suggestive of a perforated viscus. Radiographic data revealed retroperitoneal, mediastinal, and free intraperitoneal air, along with intramural bowel wall air. PMID- 1925514 TI - Port-A-Cath: a study of complication rates. AB - Venous access can be a difficult problem for patients receiving intravenous medications, such as chemotherapy, over long periods of time. Totally implanted venous access devices, such as the Port-A-Cath TM (Pharmacia Deltec, St. Paul, MN) have been introduced as a solution to the problem of venous access. These devices are marketed as a safe, reliable method of venous access. Between January 1986 and December 1988, one hundred sixty patients had Port-A-Caths implanted at Sioux Valley Hospital. The medical records of these patients were reviewed to determine the type and rates of complications with the Port-A-Cath. Complications included pneumothoracies, extravasation of injected substances, difficulty aspirating blood, occlusion and sepsis. This article describes the results of our study and a review of the literature. PMID- 1925515 TI - Transfer of Chernobyl fallout radionuclides from feed to growing rabbits: cesium 137 balance. AB - Intake, excretion and retention of gamma-emitting radionuclides were assessed in male rabbits fed a radioactive pelleted diet (137Cs = 858 Bq kg-1 as fed) containing 40% dehydrated alfalfa meal contaminated by Chernobyl fallout. In order to evaluate radionuclide retention, an experiment was carried out on 33 animals as follows: nine rabbits were slaughtered at the beginning of the trial, six were fed a radioactive diet for 42 days, six a radioactive diet for 21 days, six a radioactive diet for 21 days and a normal diet (137Cs = 112 Bq kg-1 as fed) for the following 21 days and six a normal diet for 42 days. All the animals were housed in individual metabolism cages throughout the trial. All faeces and urine were collected and analyzed separately and live weight and feed intake were measured on a weekly basis. At the end of the trial all the animals were slaughtered and the activities of net body and muscles were determined. Cesium 137, 134Cs, 103Ru, 106Ru, 125Sb, 110mAg and 40K were measured by gamma spectroscopy. More than 85% of ingested cesium was excreted through faeces and urine (fecal much greater than urinary) and the retained 137Cs in the carcass of the more contaminated animals was only 3% of the total ingested. The concentration of total cesium in muscle reached a maximum value of 156 Bq kg-1, much lower than the EEC guideline (600 Bq kg-1), and the biological half-life for 137Cs was calculated to be 11 days. The feed-body accumulation factors were determined in net body and muscle. PMID- 1925516 TI - Selenium in human milk and dietary selenium intake by Greeks. AB - Fluorimetric determination of selenium in colostrum, transitional and mature human milk gave the following concentrations (mean and standard deviation): 41 +/ 16, 23 +/- 6 and 17 +/- 3 ng Se ml-1, respectively. The ranges for each kind of milk, especially for mature milk, were narrow. For all cases studied, the Se concentration in milk decreased with lactation time, reaching a plateau, at 17 ng Se ml-1, after 20 days. It is estimated that breast-fed-only babies in Greece receive approximately 5-11 micrograms Se day-1 up to 6 months of age. From consumed food data it was estimated that adult Greeks receive 100 +/- 6 micrograms Se day-1, in close agreement with our previously determined value of 110 micrograms Se day-1 estimated from food disappearance data. PMID- 1925517 TI - Concentrations of lead, cadmium, mercury and copper in mushrooms in the vicinity of a lead smelter. AB - The concentrations of four heavy metals in 149 samples of mushroom fruiting bodies, representing 11 species, mainly all edible, were determined by atomic absorption spectroscopy. The mushrooms were collected up to a distance of 6 km from a lead smelter in central Bohemia (Czechoslovakia) in operation since 1786. Lead was accumulated extensively by Lepiota rhacodes and Lepista nuda. Among other species, significant accumulation was found up to a distance of 1 km from the source. Concentrations of greater than 100 mg kg-1 dry matter were often determined. The safe limit of 5 mg kg-1 dry matter was exceeded in most samples collected at distances of up to 6 km from the source. Concentrations of cadmium in the polluted area were generally significantly higher than in other parts of Bohemia. Cadmium was extensively accumulated by the toxic Amanita muscaria, but also by the edible Boletus edulis and Amanita rubescens, with mean values 28.6, 15.2 and 12.3 mg Cd kg-1 dry matter, respectively. The Czechoslovakian statutory limit is 0.5 mg Cd kg-1 dry matter. Statistically significant linear correlations between lead and cadmium concentrations were found only for Boletus edulis and Paxillus involutus. Mercury was accumulated by Lepista nuda and Lepiota rhacodes; mean values of 11.9 and 6.5 mg Hg kg-1 dry matter, respectively, were found. Concentrations of mercury in most species from the study area were higher than in those from other parts of Bohemia. Lepiota rhacodes and Lepista nuda also accumulated copper extensively with mean values of 280 and 193 mg Cu kg-1 dry matter, respectively. PMID- 1925518 TI - Evolution of trimethylarsine by a Penicillium sp. isolated from agricultural evaporation pond water. AB - Arsenicals are used in agriculture as pesticides and defoliants. In the Central Valley of California, arsenic is present in soil at naturally high concentrations, being derived from marine sedimentary parent material of the Coastal Range. Due to intense agricultural irrigation, soluble arsenic is leached from the soil and accumulates in evaporation ponds where it may pose an environmental threat to the waterfowl and wildlife. A Penicillium sp. isolated from evaporation pond water was found to be capable of methylating and subsequently volatilizing organic arsenic. The major focus of this study was to characterize the environmental conditions, including culture media, arsenic substrates, pH, temperature, and the presence of phosphates, carbohydrates and amino acids on the methylation of arsenic. Trimethylarsine was monitored by gas chromatography (GC)-flame ionization detection and identified by GC-mass spectrometry. The conditions or additions for optimum trimethylarsine production were: a minimal medium in which 100 mgl-1 methylarsonic acid served as the arsenic source, pH 5-6, temperature of incubation 20 degrees C, and phosphate concentration of 0.1-50 mM (KH2PO4). The addition of carbohydrates and sugar acids to the minimal medium suppressed trimethylarsine production. The amino acids phenylalanine, isoleucine, and glutamine promoted trimethylarsine production with an enhancement ranging from 10.2- to 11.6-fold over the control without amino acid supplementation. The information obtained from this study may be useful in developing a bioremediation approach in trapping the arsenic gas evolved from soil or water as a mitigation alternative in the cleanup of arsenic contamination. PMID- 1925520 TI - Radioactivity in environmental samples taken in the Sellafield, Ravenglass and Morecambe Bay areas of west Cumbria. AB - Seaborne sediments deposited in the estuaries of the Esk, Duddon, Leven and Kent have been analysed for fission products and actinides discharged in waste from the Sellafield processing works in west Cumbria, and the values compared with the generally expected values due to fallout from atmospheric nuclear weapons tests. Analyses of tissues from sheep grazing the marshes of these estuaries show that the internal radiation dose of the general public through eating mutton or liver from these animals would be at most a few percent of recommended limits. Analytical data are presented on the actinide content of beef cattle, and on potato crops grown under field conditions; these data show that, as with the sheep data, the radiation dose to the consumer would be small. PMID- 1925519 TI - Blood lead level of Cairo traffic policemen. AB - Blood lead level, haemoglobin concentration (Hb) and urinary delta-aminolevulenic acid (ALA) were determined for 126 traffic policemen and a control group of 50 office-based policemen of Cairo city. Mean blood lead level and Hb of traffic policemen were significantly higher than those of the controls; ALA of both groups were similar. The blood lead level of traffic policemen was not related to age, duration of employment or Hb. Although the observed blood lead level of Cairo traffic policemen (29.2 +/- 7.5 microns dl-1) may be considered acceptable for their occupation, it indicates a potential risk from traffic-exhaust-induced air pollution for other groups of the Cairo population such as children and pregnant women. PMID- 1925521 TI - The changing environment of a desert boomtown. AB - World population growth has prompted the exploration and habitation of geographical regions previously considered undesirable or unsuitable for human comfort. The impact of humans and their civilization on desert regions, where water and vegetation are scarce, is not well understood. The high plains desert of the southwestern United States is the fastest growing region of the nation. Historically, the desert atmosphere was distinguished by extraordinary visibility and negligible particle and chemical pollution. Unfortunately, visitors and residents of the region have perceived a decline in the air quality during a 15 20-year period which corresponds to a rapid influx of population and the development of isolated urban areas. This study attempts to assess the relative impacts of demography, meteorology and air chemistry on the air quality of a rapidly growing, small city located in the Mohave Valley on the Nevada/Arizona border. Statistically significant trends were identified in the local meteorology and air quality over a 10-year period. Temperature and relative humidity values were observed to increase at the urban site. Increases were also noted in the concentrations of total suspended particulates (TSP) and the oxides of nitrogen. Observations at the urban site were compared with similar measurements at nearby non-urban sites and with the results of studies at two larger cities in the desert southwest, Phoenix and Tucson, AZ. Conclusions based on the combined analyses indicate that the desert environment has been strongly influenced in the immediate urban area and that the changes are due primarily to demographic influences. Changes in urban air quality observed in the Mohave Valley were more pronounced and were apparent over a shorter period of time than air quality changes observed elsewhere in the southwest. PMID- 1925522 TI - Concentrations of radiocesium and potassium in basidiomycetes collected in Japan. AB - Concentrations of 137Cs, 134Cs and 40K in about 60 mushroom samples (fruit bodies of basidiomycetes) belonging to 25 species collected in Japan have been studied. The levels of 137Cs varied very widely, ranging from less than 3 to 1520 Bq kg-1 (dry wt), while those of 40K were relatively constant. Concentrations of 137Cs in common edible mushrooms of Japan such as Lentinus edodes, Flammulina velutipes, Pleurotus ostreatus and Pholiota nameko were low (normally less than 50 Bq kg-1, dry wt). Concentrations of 134Cs in many samples were below the limit of detection (usually less than 5 Bq kg-1, dry wt). The median concentrations of 137Cs and 40K were 41 (dry wt) and 1150 Bq kg-1 (dry wt), respectively. From the 137Cs/40K ratios it was found that cesium rather than potassium was selectively taken up from the soils by fungi such as Suillus granulatus and Lactarius hatsudake. The 134Cs/137Cs ratios in mushrooms are related to the depth of the mycelium in the soil. The effective dose equivalent due to the dietary intake of radiocesium through mushrooms was estimated to be only 1.6 x 10(-7) Sv. PMID- 1925524 TI - The reactivity of EDTA, copper ion, and copper citrate with metallothioneins isolated from the digestive gland of cadmium-contaminated lobster (Homarus americanus). AB - The reactivity of EDTA, Cu2+, and copper citrate with two metallothionein preparations (MT-1 and MT-2) isolated from the digestive gland of Cd-contaminated American lobster (Homarus americanus) was studied. Under pseudo-first-order conditions, metallothioneins reacted with EDTA for removal of Cd2+ in a multiphasic manner. Cadmium(+II) removal by Cu2+ was complex and non stoichiometric, suggesting different binding sites. Rabbit liver metallothionein reacted similarly. Cadmium removal from lobster metallothionein by copper citrate was slow and triphasic in nature. EDTA removed Cu2+ from lobster metallothionein very slowly. PMID- 1925523 TI - Isolation and characterization of metal-binding proteins (metallothioneins) from lobster digestive gland (Homarus americanus). AB - Two metallothionein (low-molecular-weight, metal-binding proteins) preparations, MT-1 and MT-2, have been isolated from the digestive gland of American lobster (Homarus americanus) contaminated with Cd. MT-1 contains Cd- and Cu-binding proteins, whereas MT-2 is a reasonably pure Cd-binding protein. The properties of MT-1 and MT-2 with respect to amino acid and elemental compositions, heat stabilities, polarographic, high-performance liquid chromatography (HPLC), and isoelectric focussing behaviors are reported. Lobster metallothioneins share a number of similarities with mammalian metallothioneins with respect to the presence of Cd and Cu, apparent molecular weights, amino acid compositions, UV absorption spectra at various pH, and polarographic behavior, but differ substantially in their electrophoretic behavior. PMID- 1925525 TI - Atomic absorption spectrometric determination of zinc, copper, and selenium in fish from Lake Tanganyika, Burundi, Africa. AB - Atomic absorption spectrometric determination of zinc, copper and selenium in fish from Lake Tanganyika (Burundi) shows that, although this lake is not polluted, trace element intake by fish contributes an important part of the elemental intake by man. No correlations were found between trace element levels in the fish and fish lipid and protein content. Copper and zinc were positively and highly correlated (P less than 0.005). Interspecies comparison for trace element content of fish samples is discussed. Unless the level of water pollution is taken into account, intraspecies variation cannot be evaluated. PMID- 1925526 TI - Estimated dietary intake of lead and cadmium and their concentration in blood. AB - Dietary intake of lead and cadmium and the concentration of Pb and Cd in blood were determined for 42 non-smoking subjects not occupationally exposed to Pb or Cd. The aim of the study was to analyze: (i) the relation between calculated dietary intake of Pb and Cd and the concentration of these metals in blood; and (ii) the methodological problems associated with these two measurements of exposure. The mean dietary intakes of Cd and Pb were 14.5 (SD, 3.1) and 52.9 (SD, 17.9) micrograms day-1, respectively. The concentrations of Pb and Cd in blood were 0.28 mumol l-1 (SD, 0.12) and less than 0.1 microgram l-1, respectively. The relation between dietary intake and concentration in blood was similar to that found in other countries. However, the distributions of these two variables were quite different. This suggests that dietary intake does not accurately reflect the concentration of lead in blood. The methodological problems associated with estimating the dietary intake of toxic metals were: mistakes in keeping food diaries; errors in transferring data from diaries to the computer; invalid food composition or recipe data in the data base used in the calculations. The concentration of Pb and Cd in blood is not necessarily a good indicator of exposure, since only a small proportion of the total body burden is in the blood, and interactions of Pb and Cd with other food constituents during absorption are possible. PMID- 1925527 TI - Uptake of radiocesium by mushrooms. AB - After the Chernobyl accident in April 1986 the 134Cs, 137Cs and 40K activity of mushrooms of different genera and their corresponding soils from woods located in the province of Umbria (Italy) was determined. The results indicated: a temporally increasing trend for 137Cs up to a "limit value" depending on local fallout in 1986; different cesium concentrations in various mushroom genera; and uptake of potassium from soil that did not appear to compete with cesium uptake. No reliable correlation can be inferred between the cesium content of the soil and those of mushrooms. PMID- 1925529 TI - The best of times, the worst of times. PMID- 1925528 TI - Radionuclide contamination of foods imported into Iraq following the Chernobyl nuclear reactor accident. AB - Since early 1986, a monitoring program for radionuclides in imported foods has been carried out by the Iraqi Atomic Energy Commission. After the Chernobyl nuclear reactor accident in the Soviet Union, the program was expanded; our laboratory was officially designated by the Iraqi Government to measure radionuclide activity concentrations in foodstuff imported from countries known to be severely contaminated by Chernobyl radioactive fallout. Gamma-spectrometric analysis was used. Food items such as powdered milk, lamb meat, poultry, cereals and grains imported into Iraq before the Chernobyl accident did not contain any detectable fission products. However, all lamb meat, 81% of the lentil, 44% of the powdered milk and chick-pea, and 17% of the roast beef samples were contaminated with 137Cs or 134Cs and 137Cs. The highest 137Cs contamination levels found were 82, 147, 420, 6 and 4 Bq kg-1, respectively. Contamination by 134Cs was approximately 50% of the values given above. PMID- 1925530 TI - Monsanto dioxin studies. PMID- 1925531 TI - US restrictions on foreign visitors and immigrants with the AIDS virus could once again endanger next May's Eighth International AIDS Congress. PMID- 1925532 TI - Healy gets off to a fast start. PMID- 1925533 TI - MRI--safety issues stimulate concern. PMID- 1925534 TI - Chernobyl's cloud: a lighter shade of gray. PMID- 1925535 TI - How parents make their mark on genes. PMID- 1925536 TI - Cell cycle research: down to the nitty gritty. PMID- 1925537 TI - Finding DNA sequencing errors. PMID- 1925538 TI - Electronic data publishing and GenBank. AB - GenBank, the national repository for nucleotide sequence data, has implemented a new model of scientific data management, which we term electronic data publishing. In traditional publishing, both scientific conclusions and supporting data are communicated via the printed page, and in electronic journal publishing, both types of information are communicated via electronic media. In electronic data publishing, by contrast, conclusions are published in a journal while data are published via a network-accessible, electronic database. PMID- 1925539 TI - Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations. AB - The crystal structure of a murine adenosine deaminase complexed with 6-hydroxyl 1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, has been determined and refined at 2.4 angstrom resolution. The structure is folded as an eight-stranded parallel alpha/beta barrel with a deep pocket at the beta barrel COOH-terminal end wherein the inhibitor and a zinc are bound and completely sequestered. The presence of the zinc cofactor and the precise structure of the bound analog were not previously known. The 6R isomer of the analog is very tightly held in place by the coordination of the 6-hydroxyl to the zinc and the formation of nine hydrogen bonds. On the basis of the structure of the complex a stereoselective addition-elimination or SN2 mechanism of the enzyme is proposed with the zinc atom and the Glu and Asp residues playing key roles. A molecular explanation of a hereditary disease caused by several point mutations of an enzyme is also presented. PMID- 1925540 TI - A neuron-silicon junction: a Retzius cell of the leech on an insulated-gate field effect transistor. AB - An identified neuron of the leech, a Retzius cell, has been attached to the open gate of a p-channel field-effect transistor. Action potentials, spontaneous or stimulated, modulate directly the source-drain current in silicon. The electronic signals match the shape of the action potential. The average voltage on the gate was up to 25 percent of the intracellular voltage change. Occasionally weak signals that resemble the first derivative of the action potential were observed. The junctions can be described by a model that includes capacitive coupling of the plasma membrane and the gate oxide and that accounts for variable resistance of the seal. PMID- 1925541 TI - Identification of the DNA binding site for NGFI-B by genetic selection in yeast. AB - An in vivo selection system for isolating targets of DNA binding proteins in yeast was developed and used to identify the DNA binding site for the NGFI-B protein, a member of the steroid-thyroid hormone receptor superfamily. The feasibility of the technique was verified by selecting DNA fragments that contained binding sites for GCN4, a well-characterized yeast transcriptional activator. The DNA binding domain of NGFI-B, expressed as part of a LexA-NGFI-B GAL4 chimeric activator, was then used to isolate a rat genomic DNA fragment that contained an NGFI-B binding site. The NGFI-B response element (NBRE) is similar to but functionally distinct from elements recognized by the estrogen and thyroid hormone receptors and the hormone receptor-like proteins COUP-TF, CF1, and H 2RIIBP. Cotransfection experiments in mammalian cells demonstrated that NGFI-B can activate transcription from the NBRE with or without its putative ligand binding domain. PMID- 1925542 TI - NMR studies of the structure and dynamics of membrane-bound bacteriophage Pf1 coat protein. AB - Filamentous bacteriophage coat protein undergoes a remarkable structural transition during the viral assembly process as it is transferred from the membrane environment of the cell, where it spans the phospholipid bilayer, to the newly extruded virus particles. Nuclear magnetic resonance (NMR) studies show the membrane-bound form of the 46-residue Pf1 coat protein to be surprisingly complex with five distinct regions. The secondary structure consists of a long hydrophobic helix (residues 19 to 42) that spans the bilayer and a short amphipathic helix (residues 6 to 13) parallel to the plane of the bilayer. The NH2-terminus (residues 1 to 5), the COOH-terminus (residues 43 to 46), and residues 14 to 18 connecting the two helices are mobile. By comparing the structure and dynamics of the membrane-bound coat protein with that of the viral form as determined by NMR and neutron diffraction, essential features of assembly process can be identified. PMID- 1925543 TI - Membrane-mediated assembly of filamentous bacteriophage Pf1 coat protein. AB - Filamentous bacteriophage Pf1 assembles by a membrane-mediated process during which the viral DNA is secreted through the membrane while being encapsulated by the major coat protein. Neutron diffraction studies showed that in the virus most of the coat protein consists of two alpha-helical segments arranged end-to-end with an intervening mobile surface loop. Nuclear magnetic resonance studies of the coat protein in the membrane-bound form have shown that the secondary structure is essentially identical to that in the intact virus. A comparison indicates that during membrane-mediated viral assembly, while the secondary structure of the coat protein is largely conserved, its tertiary structure changes substantially. PMID- 1925544 TI - Induction of Plasmodium falciparum transmission-blocking antibodies by recombinant vaccinia virus. AB - Many candidate antigens of malaria vaccines have limited immunological recognition. One exception is Pfs25, a cysteine-rich, 25-kilodalton sexual stage surface protein of Plasmodium falciparum. Pfs25 is a target of monoclonal antibodies that block transmission of malaria from vertebrate host to mosquito vector. The surface of mammalian cells infected with a recombinant vaccinia virus that expressed Pfs25 specifically bound transmission-blocking monoclonal antibodies. Furthermore, major histocompatibility complex-disparate congenic mouse strains immunized with recombinant Pfs25 elicited transmission-blocking antibodies, demonstrating that the capacity to develop transmission-blocking antibodies is not genetically restricted in mice. Live recombinant viruses may provide an inexpensive, easily administered alternative to subunit vaccines prepared from purified recombinant proteins to block transmission of malaria in developing countries. PMID- 1925545 TI - Two- rather than three-dimensional representation of saccades in monkey superior colliculus. AB - Saccades are controlled by neurons in the brainstem reticular formation that receive input from the superior colliculus and cortex. Recently two quantitative models have been proposed for the role of the colliculus in the generation of three-dimensional eye movements. In order to test these models, three-dimensional eye movements were measured in the alert monkey to investigate whether the saccadic motor map of the superior colliculus is two-dimensional, representing retinal target vectors, or three-dimensional, representing three-dimensional motor error for the rotation of the eye. Electrical stimulation of the superior colliculus produced two-dimensional, not three-dimensional, eye movements. It is therefore concluded that the collicular motor map is two-dimensional. PMID- 1925546 TI - Neuronal activity in narcolepsy: identification of cataplexy-related cells in the medial medulla. AB - Narcolepsy is a neurological disorder characterized by sleepiness and episodes of cataplexy. Cataplexy is an abrupt loss of muscle tone, most often triggered by sudden, strong emotions. A subset of cells in the medial medulla of the narcoleptic dog discharged at high rates only in cataplexy and rapid eye movement (REM) sleep. These cells were noncholinergic and were localized to ventromedial and caudal portions of the nucleus magnocellularis. The localization and discharge pattern of these cells indicate that cataplexy results from a triggering in waking of the neurons responsible for the suppression of muscle tone in REM sleep. However, most medullary cells were inactive during cataplexy but were active during REM sleep. These data demonstrate that cataplexy is a distinct behavioral state, differing from other sleep and waking states in its pattern of brainstem neuronal activity. PMID- 1925547 TI - Receptor-mediated activation of immunodeficiency viruses in viral fusion. PMID- 1925548 TI - Brain tumor incidence at Los Alamos. PMID- 1925550 TI - Peer review and patent rights. PMID- 1925549 TI - Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. AB - The sequence reported in our 22 March 1991 report "Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NFkappaB" [Science 251, 1490 (1991)], contained some errors. Resequencing under strong denaturing conditions revealed three insertions at nucleotide positions 1194, 1212, and 1220, which changed the AA sequence from RSAR-PRLGP to QISQASALAP (residues 372 to 380), thus accounting for some of the divergence in this region. A corrected sequence has been sent to GenBank. PMID- 1925552 TI - A is for apple, Alar, and ... alarmist? PMID- 1925551 TI - Establishment of the mesoderm-neuroectoderm boundary in the Drosophila embryo. AB - A gradient of the maternal morphogen dorsal establishes asymmetric patterns of gene expression along the dorsal-ventral axis of early embryos and activates the regulatory genes twist and snail, which are responsible for the differentiation of the ventral mesoderm. Expression of snail is restricted to the presumptive mesoderm, and the sharp lateral limits of this expression help to define the mesoderm-neuroectoderm boundary by repressing the expression of regulatory genes that are responsible for the differentiation of the neuroectoderm. The snail gene encodes a zinc finger protein, and neuroectodermal genes that are normally restricted to ventral-lateral regions of early embryos are expressed throughout ventral regions of snail- mutants. The formation of the sharp snail border involves dosage-sensitive interactions between dorsal and twist, which encode regulatory proteins that are related to the mammalian transcription factors NF-kB and MyoD, respectively. PMID- 1925553 TI - Free speech and clinical trials. PMID- 1925554 TI - Emphasizing the health in NIH. PMID- 1925555 TI - Glenn uncovers the great pizza scandal. PMID- 1925557 TI - East Germany: science in the disservice of the state. PMID- 1925558 TI - A hand on the bird--and one on the bush. PMID- 1925556 TI - Reproductive toxicity: regs slow to change. PMID- 1925559 TI - Transgenic animals may be down on the pharm. PMID- 1925560 TI - Echo-planar imaging: magnetic resonance imaging in a fraction of a second. AB - Progress has recently been made in implementing magnetic resonance imaging (MRI) techniques that can be used to obtain images in a fraction of a second rather than in minutes. Echo-planar imaging (EPI) uses only one nuclear spin excitation per image and lends itself to a variety of critical medical and scientific applications. Among these are evaluation of cardiac function in real time, mapping of water diffusion and temperature in tissue, mapping of organ blood pool and perfusion, functional imaging of the central nervous system, depiction of blood and cerebrospinal fluid flow dynamics, and movie imaging of the mobile fetus in utero. Through shortened patient examination times, higher patient throughput, and lower cost per MRI examination, EPI may become a powerful tool for early diagnosis of some common and potentially treatable diseases such as ischemic heart disease, stroke, and cancer. PMID- 1925561 TI - Determination of macromolecular structures from anomalous diffraction of synchrotron radiation. AB - Resonance between beams of x-ray waves and electronic transitions from bound atomic orbitals leads to a phenomenon known as anomalous scattering. This effect can be exploited in x-ray crystallographic studies on biological macromolecules by making diffraction measurements at selected wavelengths associated with a particular resonant transition. In this manner the problem of determining the three-dimensional structure of thousands of atoms is reduced to that of initially solving for a few anomalous scattering centers that can then be used as a reference for developing the entire structure. This method of multiwavelength anomalous diffraction has now been applied in a number of structure determinations. Optimal experiments require appropriate synchrotron instrumentation, careful experimental design, and sophisticated analytical procedures. There are rich opportunities for future applications. PMID- 1925562 TI - Large-scale and automated DNA sequence determination. AB - DNA sequence analysis is a multistage process that includes the preparation of DNA, its fragmentation and base analysis, and the interpretation of the resulting sequence information. New technological advances have led to the automation of certain steps in this process and have raised the possibility of large-scale DNA sequencing efforts in the near future [for example, 1 million base pairs (Mb) per year]. New sequencing methodologies, fully automated instrumentation, and improvements in sequencing-related computational resources may render genome-size sequencing projects (100 Mb or larger) feasible during the next 5 to 10 years. PMID- 1925563 TI - Detection of somatic DNA recombination in the transgenic mouse brain. AB - A DNA construct containing the bacterial beta-galactosidase gene (lacZ) was used to study somatic DNA recombination in the transgenic mouse brain. Recombination positive areas of the adult brain were stained blue with X-gal, a substrate of beta-galactosidase. Blue-colored cells appeared soon after birth, and continued to emerge in postnatal tissue. Staining was prominent in sensory as opposed to motor regions of the brain, and was present in more than 70 discrete areas of the nervous system. The possibility of DNA rearrangement is discussed with respect to the development of the central nervous system. PMID- 1925564 TI - A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. AB - Alzheimer's disease is a form of localized amyloidosis characterized by cerebral cortical amyloid plaques, neurofibrillary tangles, and amyloid deposits within the walls of leptomeningeal vessels. Although most cases of Alzheimer's disease are sporadic, kindreds with autosomal-dominant inheritance of the syndrome suggest that a single mutation may be important in pathogenesis. Direct sequencing of DNA from a family with autopsy-proven Alzheimer's disease revealed a single amino acid substitution (Phe for Val) in the transmembrane domain of the amyloid precursor protein. This mutation correlates with the presence of Alzheimer's disease in all patients in this study, and may be the inherited factor causing both amyloid fibril formation and dementia. PMID- 1925565 TI - Flying into the future. PMID- 1925566 TI - Research on animals: unforseen benefits. PMID- 1925567 TI - NIH Director Healy back in charge of misconduct office. PMID- 1925568 TI - Genome patent fight erupts. PMID- 1925569 TI - Edelman: bye, bye Rockefeller. PMID- 1925570 TI - A window on life in the Bronze Age. The remains of a 4000-year-old man may shed light on the racial structure and culture of early Europe. PMID- 1925571 TI - JAMA gets into an Indian herbal jam. PMID- 1925572 TI - Leroy Hood to move north. PMID- 1925573 TI - Malaria parasite gaining ground against science. PMID- 1925574 TI - Improvements seen for RU-486 abortions. PMID- 1925575 TI - Feminist group dissents on RU-486 use for abortion. PMID- 1925576 TI - Alcoholism gene: coming or going? PMID- 1925577 TI - Genome databases. PMID- 1925578 TI - The human genome initiative--do databases reflect current progress? PMID- 1925579 TI - Toward cloning and mapping the genome of Drosophila. AB - An ultimate goal of Drosophila genetics is to identify and define the functions of all the genes in the organism. Traditional approaches based on the isolation of mutant genes have been extraordinary fruitful. Recent advances in the manipulation and analysis of large DNA fragments have made it possible to develop detailed molecular maps of the Drosophila genome as the initial steps in determining the complete DNA sequence. PMID- 1925580 TI - Genome maps 1991 [wall chart]. PMID- 1925581 TI - Structure and stability of X.G.C mismatches in the third strand of intramolecular triplexes. AB - Intramolecular DNA triplexes that contain eight base triplets formed from the folding of a single DNA strand tolerate a single X.G.C mismatch in the third strand at acidic pH. The structure and relative stability of all four triplets that are possible involving a G.C Watson-Crick base pair were determined with one and two-dimensional proton nuclear magnetic resonance techniques. Triplexes containing A.G.C, G.G.C, or T.G.C triplets were less stable than the corresponding parent molecule containing a C.G.C triplet. However, all mismatched bases formed specific hydrogen bonds in the major groove of the double helix. The relative effect of these mismatches on the stability of the triplex differs from the effect assayed (under different conditions) by two-dimensional gel electrophoresis and DNA cleavage with oligonucleotide EDTA.Fe(II). PMID- 1925582 TI - Defining protective responses to pathogens: cytokine profiles in leprosy lesions. AB - The immunological mechanisms required to engender resistance have been defined in few infectious diseases of man, and the role of specific cytokines is unclear. Leprosy presents clinically as a spectrum in which resistance correlates with cell-mediated immunity to the pathogen. To assess in situ cytokine patterns, messenger RNA extracted from leprosy skin biopsy specimens was amplified by the polymerase chain reaction with 14 cytokine-specific primers. In lesions of the resistant form of the disease, messenger RNAs coding for interleukin-2 and interferon-gamma were most evident. In contrast, messenger RNAs for interleukin 4, interleukin-5, and interleukin-10 predominated in the multibacillary form. Thus, resistance and susceptibility were correlated with distinct patterns of cytokine production. PMID- 1925583 TI - Cell cycle dependence of laminar determination in developing neocortex. AB - The neocortex is patterned in layers of neurons that are generated in an orderly sequence during development. This correlation between cell birthday and laminar fate prompted an examination of how neuronal phenotypes are determined in the developing cortex. At various times after labeling with [3H]thymidine, embryonic progenitor cells were transplanted into older host brains. The laminar fate of transplanted neurons correlates with the position of their progenitors in the cell cycle at the time of transplantation. Daughters of cells transplanted in S phase migrate to layer 2/3, as do host neurons. Progenitors transplanted later in the cell cycle, however, produce daughters that are committed to their normal, deep-layer fates. Thus, environmental factors are important determinants of laminar fate, but embryonic progenitors undergo cyclical changes in their ability to respond to such cues. PMID- 1925584 TI - Long-term high-titer neutralizing activity induced by octameric synthetic HIV-1 antigen. AB - A titer for homologous viral neutralization activity (greater than 1:19,683) was observed after a 3.5-year immunization period with an octameric, branching peptide representing the principal neutralizing determinant (PND) of the human immunodeficiency virus-1IIIB envelope protein. Booster immunizations elicited persistent and potent antibodies in guinea pigs, exceeding responses produced by a conventional bovine serum albumin conjugate by 100-fold. Peptide length, central presentation of a conserved sequence, and inclusion of an upstream sequence contributed to immunogenicity. Titers (greater than 1:1,000) of heterotypic neutralizing antibodies also developed. Octameric PND peptides are a promising approach for an acquired immunodeficiency syndrome (AIDS) vaccine. PMID- 1925585 TI - Laser ablation studies of the role of the Drosophila oocyte nucleus in pattern formation. AB - Somatic and germline cells interact during oogenesis to establish the pattern axes of the Drosophila eggshell and embryo. The role of the oocyte nucleus in pattern formation was tested with the use of laser ablation. Ablation in stage 6 to 9 egg chambers caused partial or complete ventralization of the eggshell, phenotypes similar to those of eggs produced by gurken or torpedo females. Accumulation of vasa protein at the posterior pole of treated oocytes was also disrupted. Thus the oocyte nucleus is required as late as stage 9 for dorsoventral patterning within the follicle cells and for polar plasm assembly in the oocyte. PMID- 1925586 TI - Elvis impersonator? PMID- 1925587 TI - CARET study: women included. PMID- 1925588 TI - Standardized brain mapping. PMID- 1925589 TI - Court leaves patent issue unclear. PMID- 1925590 TI - Biotech pipeline: bottleneck ahead. PMID- 1925591 TI - UN claims victory in desert war. PMID- 1925592 TI - Vitamin C gets a little respect. PMID- 1925593 TI - Duesberg vindicated? Not yet. PMID- 1925594 TI - Paint kit for cancer diagnosis. PMID- 1925595 TI - FISHing cuts the angst in amniocentesis. PMID- 1925596 TI - Short-term mortality predictions for critically ill hospitalized adults: science and ethics. AB - Modern life-sustaining therapy often succeeds in postponing death but may be ineffective at restoring health. Decisions that influence the time and circumstances of an individual's death are now common and require an accurate and comprehensive characterization of likely outcome. Evaluation of alternative outcomes requires acknowledgement that most patients find some outcomes to be worse than death. Improved understanding of major predictors of patient outcome, combined with rapidly expanding technical abilities to collect and manipulate large amounts of detailed clinical data, have created a new intellectual and technical basis for estimating outcomes from intensive medical care. Such objective probability estimates, such as the system described here, can reduce uncertainty about difficult clinical decisions and can be used by physicians, patients, and society to reorient health care toward more scientifically and ethically defensible approaches. PMID- 1925597 TI - The first step in vision: femtosecond isomerization of rhodopsin. AB - The kinetics of the primary event in vision have been resolved with the use of femtosecond optical measurement techniques. The 11-cis retinal prosthetic group of rhodopsin is excited with a 35-femtosecond pump pulse at 500 nanometers, and the transient changes in absorption are measured between 450 and 580 nanometers with a 10-femtosecond probe pulse. Within 200 femtoseconds, an increased absorption is observed between 540 and 580 nanometers, indicating the formation of photoproduct on this time scale. These measurements demonstrate that the first step in vision, the 11-cis----11-trans torsional isomerization of the rhodopsin chromophore, is essentially complete in only 200 femtoseconds. PMID- 1925598 TI - Targets for dioxin: genes for plasminogen activator inhibitor-2 and interleukin-1 beta. AB - Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD), a widespread environmental contaminant, may elicit its effects by altering gene expression in susceptible cells. Five TCDD-responsive complementary DNA clones were isolated from a human keratinocyte cell line. One of these clones encodes plasminogen activator inhibitor-2, a factor that influences growth and differentiation by regulating proteolysis of the extracellular matrix. Another encodes the cytokine interleukin 1 beta. Thus, TCDD alters the expression of growth regulatory genes and has effects similar to those of other tumor-promoting agents that affect both inflammation and differentiation. PMID- 1925599 TI - Dual role of the Drosophila pattern gene tailless in embryonic termini. AB - One of the first zygotically active genes required for formation of the terminal domains of the Drosophila embryo is tailless (tll). Expression of the tll gene is activated ectopically in gain-of-function mutants of the maternal terminal gene torso (tor); this suggests that tor normally activates the tll gene in the termini. Ectopic expression of tll under the control of an inducible promoter results in differentiation of ectopic terminal-specific structures, the Filzkorper, and leads to the activation of at least one gene, hunchback, that is required to form these structures. Ectopic expression of the tll gene also represses segmentation by repressing the gap genes Kruppel and knirps and probably also pair rule genes. PMID- 1925600 TI - Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo. AB - Corticotropin-releasing hormone (CRH) functions as a regulator of the hypothalamic-pituitary-adrenal axis and coordinator of the stress response. CRH receptors exist in peripheral sites of the immune system, and CRH promotes several immune functions in vitro. The effect of systemic immunoneutralization of CRH was tested in an experimental model of chemically induced aseptic inflammation in rats. Intraperitoneal administration of rabbit antiserum to CRH caused suppression of both inflammatory exudate volume and cell concentration by approximately 50 to 60 percent. CRH was detected in the inflamed area but not in the systemic circulation. Immunoreactive CRH is therefore produced in peripheral inflammatory sites where, in contrast to its systemic indirect immunosuppressive effects, it acts as an autocrine or paracrine inflammatory cytokine. PMID- 1925601 TI - Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. AB - To better understand the basis for human immunodeficiency virus type 1 (HIV-1) persistence and latency, the form in which viral DNA exists in the peripheral T lymphocyte reservoir of infected individuals was investigated. In asymptomatic individuals, HIV-1 was harbored predominantly as full-length, unintegrated complementary DNA. These extrachromosomal DNA forms retained the ability to integrate upon T cell activation in vitro. In patients with acquired immunodeficiency syndrome (AIDS), there was an increase in integrated relative to extrachromosomal DNA forms. By analysis of DNA from patient lymphocyte subpopulations depleted of human lymphocyte antigen-Dr receptor-positive cells, quiescent T cells were identified as the source of extrachromosomal HIV-1 DNA. Thus quiescent T lymphocytes may be a major and inducible HIV-1 reservoir in infected individuals. PMID- 1925602 TI - Stereospecific effects of inhalational general anesthetic optical isomers on nerve ion channels. AB - Although it is generally agreed that general anesthetics ultimately act on neuronal ion channels, there is considerable controversy over whether this occurs by direct binding to protein or secondarily by nonspecific perturbation of lipids. Very pure optical isomers of the inhalational general anesthetic isoflurane exhibited clear stereoselectivity in their effects on particularly sensitive ion channels in identified molluscan central nervous system neurons. At the human median effect dose (ED50) for general anesthesia, the (+)-isomer was about twofold more effective than the (-)-isomer both in eliciting the anesthetic activated potassium current IK(An) and in inhibiting a current mediated by neuronal nicotinic acetylcholine receptors. For inhibiting the much less sensitive transient potassium current IA, the (-)-isomer was marginally more potent than the (+)-isomer. Both isomers were equally effective at disrupting lipid bilayers. PMID- 1925603 TI - Reversible inhibition of tomato fruit senescence by antisense RNA. AB - Ethylene controls fruit ripening. Expression of antisense RNA to the rate limiting enzyme in the biosynthetic pathway of ethylene, 1-aminocyclopropane-1 carboxylate synthase, inhibits fruit ripening in tomato plants. Administration of exogenous ethylene or propylene reverses the inhibitory effect. This result demonstrates that ethylene is the trigger and not the by-product of ripening and raises the prospect that the life-span of plant tissues can be extended, thereby preventing spoilage. PMID- 1925604 TI - A 32-kD GTP-binding protein associated with the CD4-p56lck and CD8-p56lck T cell receptor complexes. AB - The guanosine triphosphate (GTP)-binding proteins include signal-transducing heterotrimeric G proteins (for example, Gs, Gi), smaller GTP-binding proteins that function in protein sorting, and the oncogenic protein p21ras. The T cell receptor complexes CD4-p56lck and CD8-p56lck were found to include a 32- to 33 kilodalton phosphoprotein (p32) that was recognized by an antiserum to a consensus GTP-binding region in G proteins. Immunoprecipitated CD4 and CD8 complexes bound GTP and hydrolyzed it to guanosine diphosphate (GDP). The p32 protein was covalently linked to [alpha-32P]GTP by ultraviolet photoaffinity labeling. These results demonstrate an interaction between T cell receptor complexes and an intracellular GTP-binding protein. PMID- 1925605 TI - [Comparative study between conservative orthopedic therapy and intramedullary osteosynthesis of diaphyseal tibial fractures]. AB - The authors present the results obtained in a series of 275 tibial shaft fractures, 216 of which were treated by a functional orthopaedic procedure and 59 with different kinds of nailing techniques. The results are evaluated according to the criteria established by Johner and Wruhs. "Good" results were obtained with both kinds of treatment; "excellent" results were slightly more frequent with nailing techniques, owing to better alignment and a lesser degree of shortening in the fractures, although the residual deformities after the functional orthopaedic treatment were tolerable. PMID- 1925606 TI - [Bundle nailing of forearm fractures. Indications and results]. AB - Hackethal developed the nailing procedure named after him in 1959. The rationale of Hackethal nailing is an elastic jamming, which can only be achieved by obeying four rules: jamming of the nails in the cortical window, jamming then in the waist of the medullary cavity, spreading the bunch of nails in the metaphysis and filling up the conus of the medullary cavity with short nails. We confined Hackethal nailing to closed and first-degree open fractures of the 2nd-5th sixth of the shaft of the forearm. If closed reduction and nailing were impossible, we performed a plate fixation (AO), in second- or third-degree open fractures we treated with fixators (Orthofix). In a 13-year period we performed Hackethal bundle nailing in 65 patients with 115 fractures. In 54% patients surgery was performed within the first 8 hours following admission. We used two or three nails passing the fracture and one short nail. Except for 1 case, in which we needed a plaster of Paris, we achieved rational stability. On average, the nails were removed after 11.5 months. The healing and complication rates were assessed by follow-up examination of 49 patients. The results were excellent and good in 71.5% patients, satisfactory 11.4% and poor in 17.1%. Complications consisted of a 2.1% infection rate (osteitis), 3.1% non-union, 2.1% with a synostosis, 1% refracture (during removal of the nails) and 3.1% migration of nails, combined with tendon rupture. We have seen 1 case with metallosis. In conclusion with our confined spectrum of indications Hackethal nailing is a low-risk method, which leads to a rational stability and early bone healing. PMID- 1925607 TI - [Indications for percutaneous screw fixation of scaphoid fractures]. AB - A total of 198 patients with scaphoid fracture who were treated by percutaneous screw fixation were reexamined after a mean postoperative time of 82 months. Sound radiological union and clinical healing were found in 89% of the recent fractures, 81.8% of fractures with delayed or nonunion and in 42.8% with sclerotic nonunion. Based on our experience, good results can be anticipated if the fracture is anatomically reduced and the screw correctly placed. In cases of carpal collapse, sclerotic nonunion, and or a very small proximal fragment, an open fixation method should be used. PMID- 1925608 TI - [Double-barrelled replacement-plasty of the anterior cruciate ligament with fascia lata strips]. AB - An intra-articular reconstruction of the anterior cruciate ligament (ACL) in chronic and acute ruptures is described, which we call doubling-back ACL substitution. The McIntosh graft is used to fix it, starting from the posterior origin of the ACL and passing to the anterior region of its insertion and through the anteromedial tibial head, returning over the top with isometric conditions. Since April 1987, this procedure has been applied in 60 patients this way, 48 of whom we saw again between April and June 1990. There are only 2 unstable joints; 46 patients have stable knees. Most of them are engaging in sport again. PMID- 1925609 TI - [Value of synthetic (Kennedy-LAD) augmentation in replacement of the anterior cruciate ligament]. AB - In chronically ACL-deficient knees, ACL replacement was performed in 31 cases with an one-third patellar tendon (Bruckner-Jones) and in 50 cases with a quadriceps-patellarperiosteum-patellar tendon autograft (Marshall-MacIntosh) augmented with the Kennedy LAD. Anterior laxity measured with the KT 1000 arthrometer revealed a side-to-side difference of less than or equal to 3 mm in 90% (77% without augmentation), a high rate of muscle strength quotient of uninjured to treated knee of about 1 (greater than 1 without augmentation) and early recovery of ability to participate in the same sports as before in 54% of patients (45% without augmentation) demonstrate statistically significant better results of ACL replacement when a synthetically augmented autograft was used. PMID- 1925610 TI - [Operative aspects of prosthesis change in the hip joint after fracture of the prosthesis shaft]. AB - Between 1983 and 1988 revision arthroplasty was performed in 45 patients with broken femoral stems, an average of 11 years after primary total hip replacement. There were 25 men and 20 women, with an average age of 70 years at revision. The primary endoprostheses were all cemented and of the following types: Buchholz A1 (41) Charnley-Muller (2), Weber-Huggler (1), Charnley (1). In 8 cases the femoral stem only was changed, while in 37 both components had to be replaced. The posterior approach with the patient in the lateral position gave excellent exposure of both the acetabulum and the femur. This approach gave ready access to a dorsal window, through which the broken femoral stem could be removed with a punch. To achieve stability of the femur permitting immediate full weight bearing, the femoral defect was always made good by a revision stem with at least twice the femoral diameter. In order to stabilize large acetabular defects a combination of homologous bone graft and an acetabular support ring was used. The implanted prostheses were of the revision type, cemented and individually selected in each case. It was possible to implant an adequate revision prosthesis in all cases. The following complications were noted during surgery: fracture of the femur (1) defects of the femur (5), and haemorrhages that were difficult to manage (2). It was necessary to reoperate in 2 patients, in 1 because of a stitched-up drain and in 1 because of postoperative haematoma. Postoperatively, 21 patients had cardiopulmonary complications, which were successfully treated in the intensive care unit in all cases but 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1925612 TI - [Revascularization of an incompletely amputated ear with a temporal artery fascia flap]. AB - A 14-year-old male adolescent underwent incomplete amputation of his right ear. Revascularization of the remnant was achieved by means of a temporoparietal fascial-island flap. It was sutured between the dorsal aspect of the cartilage and the dorsal skin of the ear. The postoperative course was uneventful. It healed with no complications. PMID- 1925611 TI - [Ruptured retroperitoneal bile duct cyst. An extremely rare injury after blunt abdominal trauma]. AB - Management of a retroperitoneal extrahepatic bile duct cystenteric tear at a cystenteric malformation of the intra- and extrahepatic ducts (Todani IV-A) discovered during an emergency surgical procedure following an accident is presented and the problems associated with bile duct cysts are discussed. It is pointed out that acute treatment with a simple and safe method (external Kehr-T drainage) can be successful when injuries are present, although most trauma surgeon are seldom, and many never, directly confronted with injuries attributable to these extremely rare malformations. PMID- 1925613 TI - [Experimental studies of the stability behavior of the coxal end of the femur after montage and removal of DHS implants in the intact cadaver femur]. AB - After experimental implantation in non-fractured cadaver femora, the ASIF dynamic hip screw system supported the femoral neck and the lateral proximal femur and prevents deformation, depending on the vector of the resultant force. Three positions of weight-bearing were simulated: near-axial loading of the femoral neck, standing on one leg and standing on two legs. After removal of the metal the bone breaking point was markedly lowered. PMID- 1925614 TI - [Age, activity and strength of knee ligaments]. AB - The cruciate ligaments of older persons are thought to have diminished biomechanical properties. On the other hand, joint immobilization also leads to similar functional losses in ligaments. It can be difficult to differentiate between these factors in older and immobile persons. The anterior and posterior cruciate ligaments of six younger (average age 30 years) and six older (average age 64.7 years) donors with similar levels of activity were subjected to biomechanical testing. Each sample had to meet the following conditions: appropriate age, no chronic vascular and cardiopulmonary disease found on autopsy, no signs of osteoarthrosis and no knee injuries. The material properties of maximum stress (e.g. ACL: young/old 24/21N/mm2), elastic modulus (e.g. ACL: young/old 144/129 MPa), and strain (e.g. ACL: young/old 25/28%), did not differ significantly (p less than 0.05). This indicates that older persons who are active do not necessarily show functional losses in the cruciate ligaments. Other data found in the literature can be ascribed to immobilization influences. In this data many of the older test persons had chronic vascular insufficiency, cardiopulmonary disease or malignancies. PMID- 1925615 TI - [Does lung contusion and general injury severity have an effect on the lung following intramedullary femoral nailing? An animal model]. AB - We evaluated changes in lung function after closed intramedullary femoral nailing (IMN) in sheep. The effects of isolated IMN were compared with those of nailing after lung contusion and hemorrhagic shock. In adult female merino sheep a chronic lung lymph fistula was prepared according to the method described by Staub. At day 1, group 1 received right-sided lung contusion and hemorrhagic shock to a mean blood pressure of 50 mmHg for 2 h. Group 2 was the control group. At day 3 both groups were submitted to IMN, followed by a 2-h observation period. IMN caused a transient significant increase in pulmonary artery pressure and central venous triglycerides in both groups. Chemiluminescence of isolated polymorphonuclear leukocytes (PMNL) decreased in group 1 from 2.699 +/- 0.344 to 2.460 +/- 0.187 x 10(6) cpm/25000 PMNL and increased in group 2 from 2.757 +/- 0.127 to 3.824 +/- 0.439 x 10(6) cpm/25000 PMNL. Lymph flow in group 1 increased 1.5-fold while microvascular pressure decreased. In group 2 lymph flow increased less, while MVP increased. The filtration coefficient in group 1 was 5 times (7.533 +/- 0.044) that in the control group (1.45 +/- 0.133). Calculations of permeability indicated a 2-fold increase (0.044 group 1 vs 0.026 group 2). In the presence of previous lung contusion and hemorrhagic shock there is definite lung damage from IMN. This is probably mediated by stimulation of PMNL. PMID- 1925616 TI - [The radiological Lachman test: an extremely exact and predictive method for the assessment of recent and old injuries to the cruciate ligaments]. AB - The object of this paper is to examine the efficiency of the Lachmantest in the evaluation of injuries to the cruciate ligaments. As our examinations show-100% correct results-this test gives high qualitative and quantitative evidence and furthermore complies with all the necessary demands required for a standardization of a method of measuring. The standardized X-ray-Lachman-test therefore not only shows any injuries to the cruciate ligaments in new and old injuries of the knee joint without anesthesia but is also suitable for a progress control after the restauration of the cruciate ligaments or plastic ligament surgery respectively. PMID- 1925617 TI - [Three-dimensional measurement of fracture gap motion. Biomechanical study of experimental tibial fractures with anterior clasp fixator and ring fixator]. AB - A computer-linked magnetic motion tracker was used to monitor the six components of elastic fracture motions in cadaver tibia with simulated mid-shaft oblique fractures or segmental defects. The limbs were mounted in a servo-hydraulic load frame and stabilized with an Ilizarov frame or an AO-Unifix external fixator. A cyclic load of 150 or 300 N was applied along the long axis of the tibia. Under 150 N load, elastic displacements ranged up to 1.7 mm and elastic rotations ranged up to 0.6 degrees. Under 300 N load, elastic displacements went up to 3.6 mm and elastic rotations ranged up to 1.5 degrees. Comparison of the two fixators showed that the Ilizarov permitted up to 1.75 times more axial pistoning and up to 4 times more A-P displacement. The AO-Unifix permitted up to 4 times more varus-valgus and up to 7 times more A-P angulation. The technique developed for measuring the three-dimensional motion of fractures may have wide applications in further biomechanical and fracture healing studies. PMID- 1925618 TI - [Resection debridement of the lower leg with compensatory callus distraction]. AB - In fractures with severe soft tissue defects and exposed bone, so much bone is resected in the fracture zone that the soft tissue defect can be closed with shortening of the lower leg. Subsequent osteotomy of the compact layer and callus distraction (Ilizarov method) at another level restores the tibia to its former length. Ten patients were treated, with an average healing time of 39 days per centimeter of lengthening. In all cases healing was achieved. Five patients had complications but none had any permanent sequelae. The hypermetabolism of the cell organelles in all kinds of tissue during the distraction period has a good effect on the healing of wounds and osteomyelitis. The healing process is short, so that patients are only in hospital for a relatively short time. PMID- 1925619 TI - [Indications for bipolar prosthesis in femoral neck fractures. A retrospective study of the prognosis in geriatric patients with bipolar prostheses with reference to the preoperative health status]. AB - In Germany the decision to implant a bipolar prosthesis in patients with femoral neck fracture depends mainly on the patient's age and general condition. Taking into account the clinical results to date, however, these criteria alone appear not to be adequate. In our hospital 182 patients were provided with a bipolar prosthesis between January 1986 and February 1989 after traumatic hip fracture. By June 1990, the end of this investigation, 56% had died. In a retrospective study of the 67 surviving patients 25 (6-48) months postoperatively, we found that the results obtained with this bipolar prosthesis were comparable to those seen with total hip endoprostheses according to the Harris hip function score and to radiological findings regarding the frequency of loose stems and protrusion. We also employed a standardized system to evaluate the clinical condition of each patient preoperatively as well as the intra- and postoperative complications. These clinical data were compared with the postoperative survival and the Harris hip score. We found: (1) Good to excellent results in 45% (greater than 80 points), satisfactory results in 52% (51-80 points) and poor results in 3% after a period of up to 48 months. Good to excellent functional results were frequently obtained in healthy older patients. (2) Life expectancy in our group of 182 patients was shorter than in the normal population of the same age. (3) The reduced life expectancy was not attributable to the fracture trauma or the operation but rather to preexisting unrelated causes. In fact the fracture trauma itself often appeared to be a result of the patient's preexisting bad health.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1925620 TI - [Indications for surgery in distal radius fractures]. AB - In this retrospective study, the results of conservative treatment of 406 fractures of the distal radius are analysed and the limitations of conservative therapy indicated. In all, 107 male patients (average age 45 years) and 299 women (average age 65 years) were examined. In only one-third of these cases were both radiographically and clinically. Of the primarily dislocated fractures, 19% healed in the correct anatomical position with satisfactory to good clinical results. Up to now, treatment of fractures of the distal radius with dorsal tilting has been regarded as a form of conservative therapy. Although certain types of fracture, in particular unstable ones, have always been regarded as cases for operative treatment, no attempt has ever been made to define the limits between conservative and operative treatment. Evaluation of the results clearly indicates that the classification according to Frykman, the one most commonly in use, cannot be used as a primary criterion for operative treatment. In the course of a meticulous statistical evaluation, we defined the radiological parameters precisely with reference to shortening, dorsal tilt and instability and drew up a classification to define the primary indications for operation in cases of fracture of the distal radius. Shortening by over 3mm, dorsal tilting by over 10 degrees, presence of a dorsal debris zone, rupture, or osseous avulsion of the radioulnar syndesmosis as a further instability factor show the limits of conservative therapy and are clear indications for operative treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1925621 TI - [Conservative therapy of closed, dislocated fractures of the olecranon in geriatric patients]. AB - Twenty-three patients (mean age: 81.2 years) were followed up for an average of 4.6 years after conservative treatment of olecranon fractures. Long-term subjective, objective and roentgenographic results were compared with the data for 19 operatively treated patients (mean age 45.8 years). Objectively the results were significantly poorer after conservative treatment than after operative treatment: We found 42.2% excellent and good results in the conservative group, whereas the findings were excellent or good in 84.2% of results in the operative group. The differences were found mainly in the function of the elbow joint and in the radiographic findings. In the subjective results, however, we found no statistically significant difference between the long-term results of the two groups. The results were felt to be excellent or good by 87% of the patients who had undergone conservative treatment and by 84.2% of those treated operatively. PMID- 1925622 TI - [The dynamic hip screw for the management of per- and subtrochanteric femoral fractures]. AB - A total of 125 patients with pertrochanteric or subtrochanteric fractures were treated by means of internal fixation with dynamic hip screws (DHS), and 77 were reviewed both clinically and radiologically after an average period of 29 months (6-69 months). This study included group A 2 fractures (with a large lesser trochanter fragment) and group A 3 fractures (pertrochanteric region) according to the ASIF classification, and also fractures of the proximal femoral shaft. With proper surgical technique only 5 cases of early infection (4%) were recorded. Early mobilization of these patients was possible owing to stable implants. There were 7 patients (5.6%) who died while still in hospital. Of the 77 patients in whom follow-up was possible, 76 had results falling in the very good or good categories according to the Merle d'Aubigne scheme. During this follow-up period 3 cases of implant fracture were encountered. In all other cases progression to bone union was uneventful. These results show that the use of DHS is a reliable method of stabilizing unstable pertrochanteric and subtrochanteric fractures. PMID- 1925623 TI - Cancer and hypercalcemia of malignancy: a change in focus. PMID- 1925624 TI - Bone metastases in breast cancer patients. PMID- 1925625 TI - Pharmacokinetics and therapeutic index of gallium nitrate. PMID- 1925626 TI - Studies on the mechanism of action of gallium nitrate. PMID- 1925628 TI - Gallium nitrate in the treatment of cancer-related hypercalcemia. PMID- 1925629 TI - Pathogenesis of hypercalcemia of malignancy. PMID- 1925627 TI - Clinical trials of gallium nitrate in patients with cancer-related hypercalcemia. PMID- 1925630 TI - Adjuvant radiation therapy for colon and rectal cancer. PMID- 1925631 TI - Adjuvant systemic treatment for carcinoma of the colon and rectum. PMID- 1925632 TI - Chemotherapy of advanced cancer of the colon and rectum. PMID- 1925633 TI - The therapeutic use of monoclonal antibodies in colorectal carcinoma. PMID- 1925634 TI - Arterial chemotherapy in the management of colorectal cancer: an overview. AB - We have discussed the role of arterial therapy in patients with various stages and types of colon cancer. Arterial therapy is probably not useful as an adjuvant therapy for Dukes' C colon cancer. It may, however, play a role among patients with incomplete resection of liver metastases (positive margins). A randomized trial is needed to determine the role of arterial therapy in patients who have undergone complete resection of liver metastasis. Arterial therapy does not seem justified for patients with recurrent pelvic tumors. For nonresectable liver metastases, hepatic arterial therapy induces a higher response rate than does intravenous treatment. It may also improve performance status and offer additional palliation to patients who have failed systemic chemotherapy. are refractory to systemic chemotherapy may be candidates for palliative hepatic arterial chemotherapy even out of the context of a clinical trial. Asymptomatic patients with nonresectable liver metastasis who are refractory to systemic chemotherapy should be enrolled in phase I-II arterial chemotherapy trials designed to identify optimal treatment regimens. Previously untreated asymptomatic patients wishing treatment may be enrolled in a new multi institutional phase III trial being designed to compare contemporary systemic chemotherapy with less toxic arterial therapy and combined arterial and systemic therapy. Such a new trial will have to avoid any cross-over between arms to determine the true impact of arterial therapy on survival. Regional arterial chemotherapy tries to extract the "extra mile" from marginally active drugs that have a steep dose response curve by increasing tumor drug exposure. Increased drug concentrations in the tumor may be accomplished by means of the blood vessel to-tumor concentration gradient. The technology to achieve such a gradient has involved percutaneous hepatic arterial catheters, implantable infusion pumps or ports, and external pumps. The most economic hepatic arterial delivery system for protracted arterial FUdR is an infusion pump. Despite good pharmacological rationale, an improved response rate, and good evidence for effective palliation in advanced disease, hepatic arterial therapy has not improved survival when compared with systematic intravenous treatment. Possible explanations include the following: (1) poor study design that allowed patients to cross over between arms: (2) inadequate arterial chemotherapy combination; (3) inadequate arterial chemotherapy schedule; (4) hepatobiliary toxicity levels that required cessation of hepatic arterial therapy and allowed the emergence of resistant tumor clones; and (5) systemic progression of disease. Only time will tell whether improved chemotherapy and the design of a new phase III trial will establish a beneficial role for upfront hepatic arterial therapy in asymptomatic patients with colon cancer metastatic to the liver. PMID- 1925635 TI - Introduction: timing of leukodepletion of blood products. PMID- 1925636 TI - Early damage to granulocytes during storage. PMID- 1925637 TI - The effect of leukodepletion on allogeneic donor platelet survival and refractoriness in an animal model. PMID- 1925638 TI - A comparative study of the effect of three methods of leukocyte removal on plasma histamine levels in stored human blood. PMID- 1925639 TI - Early leukocyte depletion of cellular blood components reduces red blood cell and platelet storage lesions. PMID- 1925640 TI - Prestorage leukocyte depletion: effect on leukocyte and platelet metabolites, erythrocyte lysis, metabolism, and in vivo survival. PMID- 1925641 TI - Autoimmune hepatitis. PMID- 1925642 TI - Physiology and pathophysiology of autoimmunity. PMID- 1925643 TI - The natural course and heterogeneity of autoimmune-type chronic active hepatitis. PMID- 1925644 TI - Ultrastructural lesion in autoimmune hepatitis and steps of the immune response in liver tissue. PMID- 1925645 TI - Cytoplasmic autoantigens in autoimmune hepatitis: molecular analysis and clinical relevance. PMID- 1925646 TI - The asialoglycoprotein receptor as target structure in autoimmune liver diseases. PMID- 1925647 TI - Autoimmunity and hepatotropic viruses. PMID- 1925649 TI - Experimental models of autoimmune hepatitis. PMID- 1925648 TI - The hepatitis-lupus connection. PMID- 1925650 TI - Therapeutic concepts for the management of idiopathic autoimmune chronic hepatitis. PMID- 1925651 TI - A 33-year-old woman with an autoimmune syndrome. PMID- 1925652 TI - The ontogeny of the immune response: perinatal perspectives. PMID- 1925653 TI - The potential for maternal immunization to protect against neonatal infections. PMID- 1925654 TI - Immunologic aspects of preterm labor. PMID- 1925656 TI - Immunology of preeclampsia. PMID- 1925655 TI - Antiphospholipid syndrome: laboratory concerns, fetal loss, and pregnancy management. PMID- 1925657 TI - Diagnostic methods and pitfalls in the gallbladder. PMID- 1925658 TI - The gallbladder: what if it's not stone disease? PMID- 1925659 TI - Gallstone characterization: the role of imaging. PMID- 1925660 TI - Motor function of the gallbladder: measurement and clinical significance. AB - Abnormalities in gallbladder emptying commonly occur in gallstone patients. Similar changes can be found in patients without gallstones that have disease that may predispose to stones, such as diabetes. Decreased contractility of the gallbladder can be measured clinically with variety of radiological techniques, and ultrasonography seems to have a number of advantages over others. In addition to a role in pathogenesis, decreased gallbladder emptying may determine the clearance of gallstones from the gallbladder during dissolution and after lithotripsy. PMID- 1925661 TI - Medical dissolution of gallstones with bile salts. PMID- 1925662 TI - Percutaneous cholecystolithotomy. PMID- 1925663 TI - Percutaneous dissolution of gallstones. AB - Contact dissolution with MTBE is an effective and safe method to treat symptomatic patients with cholesterol gallstones. Personnel, time, and safety factors have limited widespread use of the procedure. With current competing methods to treat gallstones, it is likely that MTBE use will be reserved for those patients who elect percutaneous therapy due to fear of surgery or anesthesia and in those elderly patients who are compromised by underlying medical conditions. PMID- 1925665 TI - Extracorporeal gallstone lithotripsy. PMID- 1925664 TI - Percutaneous ablation of the cystic duct and the gallbladder: experimental and early clinical results. PMID- 1925667 TI - Genitourinary trauma. Part 2. Bladder and urethral trauma. PMID- 1925668 TI - The Venturi water powered suction pump. PMID- 1925666 TI - Bladder training in ambulatory care management of urinary incontinence. AB - Bladder training is an effective method of managing stress, urge, and mixed urinary incontinence in the outpatient setting that is relatively free of patient risks and burden. Provided a comprehensive clinical assessment is performed to rule our other contributing pathology, urodynamic evaluation does not seem a prerequisite to selection of this treatment approach. Bladder training is easy to implement in the clinical setting, does not require special equipment, and offers the opportunity for cure or significant improvement to many incontinent individuals. We are continuing in our research efforts to document the effectiveness of behavioral therapy in the management of urinary incontinence in noninstitutionalized populations. Our goal is to develop improved behavioral techniques with better targeting of patients who will be most likely to achieve the greatest benefit from them. PMID- 1925669 TI - Stenting tips. PMID- 1925670 TI - Arthrography of painful hips following arthroplasty: digital versus plain film subtraction. AB - Digital and manual subtraction images obtained during the arthrographic evaluation of 78 painful hip prostheses were reviewed retrospectively. Revision arthroplasty was performed in 53 of these cases, and the arthrographic and surgical findings were correlated. The digital and manual subtraction images were evaluated without knowledge of the surgical results using established criteria for component loosening. Digital subtraction arthrography of the femoral component demonstrated a 96% sensitivity and 100% specificity for the diagnosis of component loosening. Sensitivity and specificity for acetabular component loosening were 83% and 80%, respectively. Plain film subtraction of the femoral component demonstrated a 79% sensitivity and 100% specificity; the sensitivity and specificity for the acetabular component were 75% and 80%, respectively. The difference between detection of femoral component loosening on digital as opposed to manual subtraction images was statistically significant (P less than 0.05). This study demonstrate that digital subtraction improves the evaluation of femoral component loosening in painful hip prostheses. PMID- 1925671 TI - Is there a relationship between femoral anteversion and leg torsion? AB - In this study, the association between increased femoral anteversion and external torsion of the leg was investigated by computed tomography in adults. In a control group of 15 women, the anteversion angle of the femoral neck measured 11 degrees +/- 9 degrees and 12 degrees +/- 9 degrees for the right and left sides, respectively. The external torsion of the leg was 40 degrees +/- 8 degrees and 39 degrees +/- 10 degrees, respectively. The patient group consisted of 16 women who were evaluated for clinical symptoms related to increased femoral anteversion. In this group, the femoral anteversion was 31 degrees +/- 7 degrees and 33 degrees +/- 7 degrees for the right and left sides, respectively, and the external torsion of the leg was 35 degrees +/- 10 degrees and 33 degrees +/- 12 degrees, respectively. There were no correlations between the degree of femoral anteversion and the degree of external torsion of the leg. This study indicates that in cases of increased femoral anteversion, compensatory external torsion of the leg does not develop regularly during growth. PMID- 1925672 TI - Magnetic resonance imaging in symptomatic Paget's disease. AB - Four patients with symptomatic Paget's disease of the appendicular skeleton were evaluated by magnetic resonance (MR) imaging. The plain film findings in each case were advanced but dissimilar. All patients had progressive symptoms of pain, and one presented with excruciating pain of short duration. The radiographic features included diffuse progressive osteolysis, cortical resorption, insufficiency fractures, bowing, and cortical and trabecular thickening. In three of the patients, MRI was performed to exclude sarcoma, revealing preservation of fatty marrow signal in all phases of Paget's disease except in patients with an acute fracture (demonstrated by MRI) and sarcoma. Small, focal, linear or oval areas of low signal seen against a background of normal marrow signal on short or long TR/TE do not mimic tumor. These findings suggest that fatty marrow signal is preserved in advanced Paget's disease unless an acute fracture or tumor is present. PMID- 1925673 TI - Bicipital groove dysplasia and medial dislocation of the biceps brachii tendon. AB - The purpose of this study was to investigate the plain film finding of dysplasia of the lesser tubercle of the humerus and its relationship to medial dislocation of the tendon of the long head of the biceps brachii muscle as diagnosed by shoulder arthrography. Of 55 patients referred for arthrography of the shoulder because of undiagnosed shoulder pain, 12 demonstrated flattening of the medial wall of the bicipital tendon groove. Of these, 58% had medial dislocation of the biceps tendon, and 43% of patients with dislocation of the biceps tendon were also shown to have a tear of the rotator cuff. Since biceps tendon pathology has long been implicated in shoulder pain and weakness, assessment of the bicipital groove may provide important information in evaluating patients with potential abnormality of the biceps tendon. PMID- 1925674 TI - Freiberg's disease in diabetes mellitus. AB - We evaluated a total of 13 cases of Freiberg's disease in patients aged 47-77 years collected over an 8-year period. Seven were associated with diabetes mellitus and one with chronic renal failure; the remainder had no underlying disease. Atrophy of intrinsic small foot muscles secondary to neuropathy, which is prevalent in diabetes mellitus, may play a part in the development of Freiberg's infraction. PMID- 1925675 TI - Medial dislocation of the patella. AB - Medial dislocation of the patella is a previously unreported entity. This disorder can be disabling to the patient and may require a hospital visit for reduction. Three cases are presented in this article in which computed tomography demonstrated the dislocation. All three patients had undergone a lateral retinacular release to the involved knee for treatment of chronic knee pain or recurrent lateral patellar subluxation. PMID- 1925676 TI - Popliteal cysts: a reassessment using magnetic resonance imaging. AB - The advent of magnetic resonance imaging (MRI) prompted the reevaluation of the incidence of popliteal cyst and its associated injuries. We reviewed more than 1000 consecutive MRI examinations of the knee performed on patients referred for evaluation of internal derangement. We report a 5% incidence of popliteal cyst, which is lower than has previously been determined. We believe that the reported higher incidence was due to arthrographic distention of normal, collapsed bursae. The strong association between popliteal cyst and tear of the medial meniscus is confirmed. We report for the first time to our knowledge the 13% association between popliteal cyst and complete tear of the anterior cruciate ligament. PMID- 1925677 TI - Radiographic findings of degeneration in cervical spines of middle-aged soccer players. AB - Twelve amateur veteran soccer players (average age 40.1 +/- 5.4 years), who began playing in their teens and who were admitted with symptoms most likely to be related to cervical spondylosis, were examined by cervical radiography. Abnormal radiographic findings included: calcification of anterior longitudinal ligament (25%), anterior (75%) and posterior vertebral spurs (75%), ossicle between spinous processes (75%), calcification of nuchal ligament (Barsony) (58%), ossicle on spinous process (25%), and bony spur of Luschka's joints (83%). It was shown in the stress distribution by finite element method analysis that the stress in heading the ball was applied mainly to the lower parts of the cervical spine. The results of this analysis also corresponded well with some of the radiographic findings. PMID- 1925678 TI - Normal values for metacarpal and phalangeal lengths in Nigerian children. AB - Metacarpal and phalangeal lengths were measured on 1290 hand radiographs of Nigerian children, aged 3-16 years. The radiographs were obtained during a combined cross-sectional and longitudinal study of growth and development. There is a linear increase in tubular bone length with age in both sexes. The girls have higher values for all the bones up to the age of 13 years when the boys overtake them. Comparison of our data with those from North American children shows that the values amongst Nigerian children are higher than White, Black American and Mexican American children. Of particular note is the difference between Black American and Nigerian figures. It is postulated that the decreased metacarpophalangeal lengths in Black Americans compared with Nigerians may be due to 'gene dilution'. PMID- 1925680 TI - Case report 686. Stress fracture at distal end of femur simulating "periosteal desmoid". AB - A 13-year-old female presented after repeated trauma with pain of the distal end of the thigh. The findings on plain films, bone scan, and CT were indeterminate. MRI accurately demonstrated a fracture line with bone marrow edema, suggesting the diagnosis of stress fracture. MRI patterns of stress fracture were considered and the importance of establishing the correct diagnosis was emphasized. PMID- 1925679 TI - Case report 668. Carbonic anhydrase II deficiency syndrome (osteopetrosis associated with renal tubular acidosis and cerebral calcification). AB - A 4-month-old infant with bronchiolitis was found to have hyperdense bones on chest roentgenograms. The diagnosis of osteopetrosis was demonstrated by generalized increased radiological bone density and by a bone biopsy showing persistence of calcified cartilage. The infant also had a mixed proximal and distal renal tubular acidosis requiring as much as 12 mEq/kg per day of sodium bicarbonate. Measurement of his erythrocyte carbonic anhydrase activity revealed a deficiency of CA II. His parents showed values of CA activity that were intermediate between controls and the proband. Thus, this is a patient with the CA II deficiency syndrome; he is the youngest reported case without any family history of osteopetrosis to be diagnosed initially on the basis of his radiographic features. PMID- 1925681 TI - Case report 687. Disseminated Mycobacterium avium-intracellulare osteomyelitis. AB - We present a patient with disseminated MAI osteomyelitis with no evidence of underlying disease or immune failure. Disseminated MAI is rare in the immunocompetent host and closely simulates malignant disease. Delayed cultures are required for precise diagnosis and optimal treatment. PMID- 1925682 TI - Case report 688. Fractures of the spinous processes of multiple thoracic vertebrae. AB - The double spinous process sign at multiple levels is a reliable indication of fractures of multiple spinous processes. When multiple thoracic vertebrate are involved, as in the patient reported here, the AP radiograph may offer the sole clue to the extent of injury on the plain films. PMID- 1925683 TI - Case report 689. Metastatic atrial myxoma to the pubis. AB - We have presented a 23-year follow-up of a patient with left atrial myxoma with continuing slowly growing, skeletal metastases. The relatively indolent nature of the metastatic disease and the lack of mitotic figures suggest that the metastatic lesions may be treated locally. The patient underwent therapeutic tumor embolization and local resection of the pelvic lesion, with good results as she continues to do well with close follow-up. PMID- 1925684 TI - Case report 690. Nodular fasciitis of the elbow. AB - Nodular fasciitis is an uncommon, benign, reactive process of the soft tissues related to the fascia. It occurs most commonly in the extremities, trunk, face, and neck. The lesion may grow rapidly and mimic a malignant process. It received little attention in the radiological literature. We describe the MRI features of nodular fasciitis in a patient with a lesion in the right elbow. PMID- 1925686 TI - The production of health and the demand for health care in Finland. AB - A structural equation model of the determinants of health and of the demand for health care, treating health status as a latent variable, was developed using cross-sectional sample survey data representing the adult noninstitutionalized population (n = 10,712) of Finland in 1987. Attention was paid to evaluating the relative effects of different factors affecting health and demand for health care in order to make generalizations for health policy. The maximum likelihood estimates of MIMIC (multiple indicators and multiple causes) models are presented. The results indicate the important role of lifestyle variables as health production factors, and stress the importance of decreasing smoking and reducing overweight as targets for health policy. Under the assumptions of the model, smoking and overweight also have considerable effects on health care utilization. The socioeconomic variables--income, education and occupation--seem to have almost equal impacts on health, although their separate direct effects are somewhat smaller than the effects of the two lifestyle factors. The results of demand for doctor visits and prescribed medicines stress factors such as time cost and the supply of doctors as important determinants of utilization, and confirm the fact that a significant portion of health utilization depends on doctors decisions and is generated by patient-doctor contacts. PMID- 1925685 TI - Case report 691. Radiation-induced osteochondromas (RIO) arising from the neural arch and producing compression of the spinal cord. AB - A case of a 16-year-old girl with a RIO of the T11 neural arch compressing the spinal cord is presented. The radiation therapy had been given after removal of a Wilms' tumor at 1 year of age. RIOs usually occur in the long bones and are diagnosed about 8 years following irradiation. Spinal cord or nerve root compression is usually associated with multiple cartilaginous exostoses. PMID- 1925688 TI - Perceptions of problematic events and quality of care among patients and parents after successful therapy of the child's malignant disease. AB - Fifty-three children (mean age 6.4 at diagnosis, 12.8 years at completion of questionnaires) identified as having acute lymphoblastic leukaemia (48) or non Hodgkin lymphoma (5) during the 11-year period of 1976-1986 participated in the present study. Patients' and parents' perceptions of malignancy-related changes in significant relationships, of treatment-related problematic events, as well as of the quality of care provided during induction and maintenance-therapy were assessed using questionnaires. The results indicated mainly positive changes in significant relationships during the chemotherapy. However, concurrent stressful life events affected the relationships adversely. Alopecia (hair loss) was the most problematic disease-related event for the patient and the patient's anorexia for the parents. Patients' complaints were most often about the quality of care during induction, namely pain, fear and insufficient information. Parents' complaints were about the lack of continuity in the staff-patient relationship during maintenance-therapy. PMID- 1925687 TI - Concern about AIDS among hospital physicians, nurses and social workers. AB - In this study, the authors examine the worry and discomfort experienced by direct care health professionals in treating AIDS patients and how their profession, attitudes, knowledge, experience and demographic characteristics influence their emotional reaction to those patients. The research focuses on experienced emotion as distinct from expressed emotion, as an important factor in explaining health behaviors among professionals. To address these issues 536 health care professionals comprising 132 physicians, 378 nurses and 26 social workers employed at a University teaching hospital in Chicago were surveyed. The findings suggest that health care workers' emotional reactions to HIV depend on the type of patient interaction. We found for all three professions, as the invasiveness of contact increased, the level of worry and amount of discomfort also increased. Nurses however, on the whole were the most adversely affected by their patient contacts. We conclude that emotional reactions in the workplace cannot be explained by cognitions, beliefs and attitudes alone. This study suggests that work roles, work assignments, and professional authority contribute to emotional reactions to patients with AIDS. PMID- 1925689 TI - Social network, social support and acute chest complaints among young and middle aged patients in an emergency department--a case-control study. AB - The risk of developing non-specific chest complaints was higher among young and middle-aged persons with a weak social network and low social support, when comparing cases with controls at a hospital emergency department (ED). The study was comprised of 62 cases; two different control groups were recruited from other patients at the medical ED (n = 67) and from patients at the surgical ED with urolithiasis or cholecystitis (n = 31). Relative risks for non-specific chest complaints were 2.3-3.4 for patients with a low score on two of the social network factors (an overall index and social anchorage) and two social support factors (emotional esteem support and support by a confidant). These results could be used for developing guidelines for a more adequate clinical management of these patients, as well as for the prevention of stress-related conditions in general. An analysis was made of the conceptual validity of the instrument used for assessing social network and social support. It was concluded that structural elements, such as social network factors, represented a more valid measurement that was less affected by subjectivity. Future research is of importance for finding overbridging concepts, rather than to further continue the dissection of presently used indices into even more 'specific' variables. PMID- 1925690 TI - Psychoactive drug use among medical doctors is higher than in the general population. AB - We surveyed a representative sample of practising physicians and a representative sample of subjects from the Swiss general population (SOMIPOPS Survey) concerning their annual use of sleeping pills and tranquillizers. 77% of the physicians (n = 466) and 72% of the general population (n = 4255) responded. After adjustment for age and sex 37.1% of the doctors (general population 21.1% P less than 0.001) claimed to have taken these drugs for therapeutic purposes. The proportion of psychiatrists who reported taking sleeping pills and tranquillizers daily (10.6%) were significantly greater than for the population of doctors as a whole and for the general population (P less than 0.05). Regular users (i.e. subjects taking one mood altering drug at least once a week) accounted for 11.1% of the medical population compared with 6.8% of the general population (P less than 0.01). This over-consumption was wholly due to the greater number of regular users of psychoactive drugs amongst doctors less than 50 years of age relative to the general population or to subjects in higher management (from P less than 0.05 to P less than 0.001). Without this specific over-use, members of the medical profession would not have been found to use more psychoactive drugs than the general population and the executives. This result suggests that it would be worth investigating the mechanisms of response and adjustment (coping) to the specific stress that appears to be inherent in the exercise of medical practice. PMID- 1925691 TI - The effects of cimetidine on the cost of ulcer disease in Sweden. AB - The economic impact of the drug cimetidine on the direct and indirect costs of ulcer disease was studied. Cimetidine appeared on the Swedish market in 1978. Unlike other innovations, whose spread is normally slow during the initial period, cimetidine was introduced very swiftly and its use quickly expanded. It was expected that it would reduce the number of elective ulcer operations, with resulting savings in medical care resources exceeding the cost of the new drug. The use of cimetidine was also expected to reduce the indirect costs related to short- and long-term illness. The aims of the study were: (1) to describe and calculate the economic impact of the introduction of cimetidine; (2) to compare the retrospective calculations with the prospective calculations; and (3) to investigate how routinely collected data could serve as a complement to studies of efficacy, effectiveness, and cost-effectiveness. Retrospective calculation of the economic effects shows that cimetidine has in fact increased the direct costs of medical care. On the other hand, the drop in indirect costs due to reduced long-term absence (disability) from work, and reduced short-term absence from work, exceeded the increase in the cost of medical care. Thus, the total economic cost of peptic ulcer disease was reduced. PMID- 1925692 TI - Epidemiology of traumatic brain injury in Johannesburg--I. Methodological issues in a developing country context. AB - Incidence studies in the developing countries present epidemiologists with unique methodological challenges for which novel solutions must be found. These challenges arise from archival inadequacies, hospital overcrowding, high violence rates, and limited research funding that necessitates low cost epidemiology. This paper describes the methods devised in Johannesburg, South Africa, in order to develop incidence estimates of determinable reliability of the morbidity and mortality arising from traumatic brain injury, and its etiology. Results are reported in Part II of the paper (p. 289). PMID- 1925693 TI - Epidemiology of traumatic brain injury in Johannesburg--II. Morbidity, mortality and etiology. AB - Using the method described in Part I (p. 283), data on the epidemiology of traumatic brain injury (TBI) in Johannesburg are presented. The overall annual incidence of TBI is 316 per 100,000. Data for Africans and Whites show marked contrasts. Among Africans, incidence is 355/100,000, with a male-female ratio of 4.4, and 763/100,000 for males aged 25-44; for Whites, it is 109/100,000 overall, with a male-female ratio of 40.1, and 419/100,000 for men aged 15-24. The overall incidence of fatal TBI is 80/100,000, with a case fatality ratio of 0.20. Interpersonal violence accounts for 51% of nonfatal TBI among Africans, as against 10% for Whites, while motor vehicle accidents cause 27% of African nonfatal TBI and 63% among Whites. Some explanatory hypotheses for this race- and sex-specific skewing of the incidence and causes of TBI are developed. PMID- 1925695 TI - Using routine surveys to measure mortality: a tool for programme managers. AB - Aid donors and recipients have begun to demand timely, population-based information for programme planning and for measuring health programme performance. Results from trials in Jordan, Syria, Djibouti and People's Democratic Republic of Yemen show that widely-used routine surveys for estimating vaccination coverage can be adapted to collect data on health indicators such as child and maternal mortality. Estimation methods must be robust and fieldwork well-supervised. Adding questions about total children ever born and surviving, the survival of the preceding birth, and the survival of sisters to such surveys, population-based estimates of the trend and recent level of childhood mortality and of the lifetime risk of maternal death can be obtained. These trials indicate that the need to monitor selected health indicators could be met through inexpensive, low-technology surveys. PMID- 1925696 TI - Qualitative methods in operations research on contraceptive distribution systems: a case study from Nigeria. AB - This article discusses the application of qualitative methods in operations research on a family planning service delivery system. Market traders in Ibadan, Nigeria were trained to sell oral contraceptives, condoms, and spermicidal foaming tablets in a collaborative research project of the Fertility Research Unit of the University College Hospital, Ibadan, and the Center for Population and Family Health of Columbia University. Focus group discussion, participant observation, and semi-structured interviews were used to investigate the cultural acceptability of distribution of contraceptives in the market places and the motivations of participating traders. The strength of the market associations was a factor influencing acceptance of the project and the number of customers for the traders' other wares were found to positively influence the volume of sales of contraceptives. Traders were motivated by the status associated with participating in a program of a well-known health institution. Findings from qualitative research suggest areas for quantitative studies and vice versa in an interactive process. PMID- 1925694 TI - Lay self-care in health: the views and perspectives of Israeli laypeople. AB - A random sample of 407 Israel laypeople was interviewed about several dimensions of their attitudes toward lay self-care in health. The dimensions studied were perceptions of laypeople's motives in undertaking self-care, views regarding the division of responsibility for individual health between laypeople and professionals, and opinions regarding the effects of lay autonomy and initiatives in health care and seven specific self-care behaviors. These attitudes were analyzed in relation to sociodemographic and health-related variables. The findings suggest that Israeli laypeople take a medically-dependent view of health care, and indicate that self-care in health is not a particularly salient or widely advocated behavior. This research complements previous studies on Israeli physicians and allied health professionals' attitudes towards self-care. PMID- 1925698 TI - Violence and families. PMID- 1925699 TI - Southeast Asian refugees and sudden unexplained death syndrome. PMID- 1925697 TI - Infant mortality among ethnic immigrant groups. AB - The numerically large and growing Indochinese refugee population has been little studied with respect to infant health. It is a population that is young, is experiencing high fertility, late onset of prenatal care, and is characterized by low socioeconomic status. Thus, it presents a high risk profile with respect to infant mortality. Using linked birth and infant death records for the San Diego metropolitan area for the period 1978-85 infant mortality rates (IMRs) were calculated for Indochinese refugee groups from Vietnam, Laos and Cambodia in comparison with other ethnic groups. We found, surprisingly, that Indochinese refugees as a group had an IMR below that for non-Hispanic Whites and substantially below that for Blacks. In general, IMRs for Indochinese refugees were similar to those for other Asian groups. These findings held even after controlling for birth weight and onset of prenatal care. The timing and causes of death suggest areas in which the IMR could drop to even lower levels with improved community outreach programs, especially among refugee groups from Laos (Hmong and Lao) who exhibited the unusual pattern of higher post-early neonatal than early neonatal mortality. PMID- 1925700 TI - The use of anatomical dolls as assessment and evidentiary tools. AB - Anatomical dolls commonly are used to assess allegations of child sexual abuse. Such assessments are based largely on interviews with children and observations of how they play with and handle the dolls. Several recent court decisions have questioned the reliability and validity of anatomical dolls as an assessment and evidentiary tool. This article reviews the literature on the use of anatomical dolls and highlights issues concerning their diagnostic and forensic efficacy. The authors identify and discuss implications of the use of these dolls for social work practice and research. PMID- 1925701 TI - Community-based spouse abuse protection and family preservation team. AB - Fragmentation and lack of communication plague agencies that serve families in which spouse abuse occurs. Spouse-abuse families may have service needs that span the fields of medical, legal, and social services; law enforcement; and employment. This article provides a brief overview of the multiple service needs of spouse-abuse families and describes a framework for developing, organizing, and implementing a community-based spouse abuse protection and family preservation team. The proposed model recognizes the needs of victims, perpetrators, and their family members. PMID- 1925702 TI - Responding to hidden abuse: a role for social work in reforming mental health systems. AB - Clients in a state-funded intensive case management program, most of whom were identified as heavy users of acute care and psychiatric emergency rooms, had undetected brutal life experiences: 50 percent were adult children of alcoholics, and many were sexually and physically abused as children or adults. None had been asked about or appropriately treated for these aspects of their background. Statistical analysis indicated high levels of correlation between exposure to alcohol abuse in the family, physical or sexual abuse, repeated hospitalization, and contemporary suffering. Social work can use this and related data to make mental health systems more responsive to clients' needs at both the clinical and systems levels. PMID- 1925703 TI - Who's afraid of the big bad wolf? Confronting wife abuse through folk stories. AB - Because many world folk stories describe wife abuse with remarkable insight, these stories are useful in addressing the sensitive issues that arise when counseling battered women. Following the views of Milton Erickson and Joan Laird about the importance of stories as a therapeutic tool, techniques were developed in a regional Coalition for Battered Women in North Carolina to use folk stories as an aid in redefining problems, increasing self-esteem, decreasing resistance, and encouraging alternative solutions to difficult situations. A case study of the use of a story in a battered women's support group session illustrates the value of folk stories in the counseling process. On the basis of experience to date, additional uses of the stories to help abused women are suggested. PMID- 1925704 TI - Abduction of children by their parents: a survey of the problem. AB - On the basis of a survey of a non-representative national sample of 371 parents who sought help from missing children's organizations, this article provides a profile of families in which children were abducted by one of the parents. Abductors were described as less educated and less likely to be employed than searching parents. In this survey, three-fourths of abducted children were younger than seven years of age; most abductions involved a single child. Although the abducting parents tended to be male (55 percent, n = 205), the proportion of female abductors was higher than in previous research. Mothers whose children were kidnapped by the father described more violence in their marriages, more fault-related reasons for divorce, and more force used in the abduction than did fathers whose children were kidnapped by the mother. The different family and social experiences of these men and women are discussed, and implications for social work practice are explored. PMID- 1925705 TI - Women and mid-life divorce: some practice issues. AB - Women who divorce during middle age face age-specific stresses, including loss of long-held social position, the possibility of overdependence on young adult children, a shrinking remarriage pool, socially denigrated body changes, and unfair labor market conditions. In assisting these women, social workers need to focus initially on grief and mourning. However, the overall treatment should emphasize changing maladaptive behavior and adverse environmental conditions. Relevant approaches include structured educational group treatment, task assignment, cognitive restructuring of maladaptive self-beliefs, reframing of the divorce experience as a challenge to growth, family treatment involving inperson contact with young adult children, and advocacy to end age discrimination in the hiring and wages of middle-aged women. PMID- 1925706 TI - The juvenilization of poverty in the 1980s. AB - This article analyzes the factors that caused the economic well-being of children in the United States to deteriorate during the 1980s. The poverty rate for children decreased through the late 1960s and the 1970s but rose during the 1980s. Young families and female-headed families were hit hardest by structural economic changes, contributing to the rise in child poverty. In addition, although more children became poor, social services provision did not increase and in many instances was cut back. The juvenilization of poverty requires social workers to place themselves in advocacy roles and to focus on poverty as a central practice concern. PMID- 1925707 TI - Gay youth support groups: an opportunity for social work intervention. PMID- 1925708 TI - [Aspects of criminal participation in suicide]. AB - The authors' aim was to draw attention to the problem of participation in suicide. Suicide associated with penal responsibility is infrequent, the authors assume, however, that it deserves more attention. When elucidating the background and objective circumstances of suicide, the detection and evidence of participation in suicide is a very difficult and responsible task. Participation in suicide is not necessarily obvious and easy to prove at first. Based on their own experience assembled during an aimed analysis of 934 cases of suicide the authors draw attention to risk situations when investigation of possible participation is justified. Obtaining more accurate and extensive information, more active detection of people responsible for this criminal activity and their punishment is according to the authors important for the prevention of suicides. PMID- 1925709 TI - [Findings in the atrioventricular node and the bundle of His in sudden and unexpected death in childhood. Histochemical study]. AB - In 21 sudden and unexpected deaths of infants and three young children who died unexpectedly with known pathological conditions the authors examined by histochemical methods the atrioventricular node and bundle of His. The activity of "glycogen dependent" phosphorylase and the PAS reaction was in the majority week or negative. The probable cause of this finding is hypoxia, although other influences cannot be ruled out (inflammation, hypotrophy, autolysis). The activities of other enzymes (oxido-reductases ATPase, acetylcholine sterase, non specific 1-naphtyl acetate esterase and acid phosphatase) were similar as in the normal conduction system. PMID- 1925710 TI - [Head injuries caused by beer glasses and bottles]. AB - The authors investigated head injuries in 23 subjects caused by beer glasses and bottles, differentiating thin-walled and thick-walled glasses, full and empty bottles and whether the injury was caused by hitting with the bottle or throwing it. A large range of injuries was found--from trivial ones to serious health damage. From the character of the injury the injuring object cannot be assessed. PMID- 1925711 TI - Patient protection and tort evasion: illiteracy revisited. PMID- 1925712 TI - 'We don't make 'em--we just fix 'em!'. PMID- 1925714 TI - Shift work, sleep quality, and worker health: a study of police officers. AB - The Planning and Analysis Unit of the Lexington Police Department changed from rotating to permanent shift assignments. We report herein the results of patrol officers' responses to the Florida Sleep Questionnaire, the SCL-90 (a symptom checklist), and absentee data. Sleep quality and sleep hygiene improved after changing from rotating to permanent shifts. The SCL-90 demonstrated improved psychologic well-being. Further, absentee rates fell from 1400 hours during the 6 months preceding the shift change to 883 hours during the 6 months following the change. We review the literature concerning the effects of shift work on worker performance. PMID- 1925713 TI - Patient reading ability: an overlooked problem in health care. AB - Health care workers often assume that patients who have completed a certain grade in school can read at that level. This study examines the relationships between patient reading ability, the last grade completed, and the reading ability necessary to comprehend commonly used written materials. We tested 528 patients during regular visits to seven outpatient clinics serving a predominantly indigent population. In addition, we analyzed the readability of 280 brochures and consent forms used in these clinics. Most patients had reading abilities on a level far below their last grade completed, while almost all materials tested were written on a level far above average patient reading ability. We conclude that patient reading ability should be routinely tested and that written materials should be developed on a level commensurate with patient reading ability. PMID- 1925715 TI - Suicide in the elderly: a two-year study of data from death certificates. AB - Data from death certificates in Kentucky in 1987 and 1988 for persons 65 years old and older were analyzed. There were 205 suicides in the 2-year study period. Suicide rates were higher for the elderly than for any other population group. White men, the group at highest risk, committed approximately 80% of the suicides in the elderly group. Suicide among minorities was rare. Self-inflicted gunshot wounds accounted for 88% of the suicides in the elderly group. Despite their high risk of suicide, elderly white men are underrepresented in terms of psychiatric admissions. PMID- 1925716 TI - Effect of anorexia nervosa on pulmonary immunocompetence. AB - Pulmonary infection due to opportunistic organisms and usually nonpathogenic mycobacteria may occur whenever immune defenses are weakened by external factors. These factors include neutropenia, treatment with corticosteroids or cytotoxic agents, previous antibiotic therapy, and nosocomial hazards (eg, catheters, ventilators). Nutritional deprivation is also often implicated as an important coexistent variable. An infection due to Mycobacterium xenopi (usually a nonpathogenic mycobacterium) in a patient with anorexia nervosa and no other predisposing factor for infection provides a model for discussing the possible effects of malnutrition on pulmonary immunocompetence. Since pulmonary infection in anorexia nervosa is often subtle, early evaluation of depressed cell-mediated immunity is appropriate. PMID- 1925717 TI - Hypermobility and deconditioning: important links to fibromyalgia/fibrositis. AB - In this study 210 patients who were identified as having fibromyalgia/fibrositis were evaluated for hypermobility of joints. The patients were then instructed to perform an exercise program, and thereafter their compliance with the program and its effect on their symptoms were evaluated. The data were then analyzed using the Student's t test and Pearson's correlation coefficient. Patients who exercised during the study had improvement. Because the hypermobile patients as a group exercised more than the nonhypermobile group, they showed greater improvement than the nonhypermobile group (58% versus 30%). Patients with fibromyalgia/fibrositis who have articular hypermobility are more likely to exercise, which will improve their symptoms. The ability to show the objective findings of hypermobility to a person with fibromyalgia/fibrositis, a diagnosis based on subjective symptoms and signs, facilitates management of the patient. These tangible signs help the patient accept and adjust to the diagnosis of fibromyalgia/fibrositis. PMID- 1925718 TI - Technique for drawing blood for cultures: is changing needles truly necessary? AB - After drawing blood for culture, medical students and house officers are often taught to change needles before inoculating the culture media. Data to support this practice have been scarce. We obtained simultaneous blood cultures on 75 hospital patients using two techniques: changing needles (C) or not changing needles (NC) before inoculating the cultures. Positive cultures judged to be contaminants were obtained in 4/75 patients in the NC group (5.3%) and in 1/75 patients in the C group (1.3%). This difference was not statistically significant. The practice of changing needles after drawing blood for culture may not be necessary, thus reducing the risk of needlestick injury. PMID- 1925720 TI - Benign and malignant neoplasms in a family with Peutz-Jeghers syndrome: study of three generations. AB - Three members of a family with Peutz-Jeghers syndrome had intussusception due to intestinal hamartomas. In addition, the grandfather had carcinoma of the jejunum, and the granddaughter had benign ovarian sex cord/stromal tumor causing sexual precocity. Benign and malignant tumors, not often associated with Peutz-Jeghers syndrome, pose a further threat in addition to the gastrointestinal bleeding and obstruction that often complicate this inherited syndrome. PMID- 1925719 TI - Phenytoin intoxication. AB - We studied the clinical features of 85 cases of phenytoin toxicity in 76 patients treated at a general hospital. Serum levels of phenytoin on admission ranged from 30.3 to 95.0 micrograms/mL (median, 46.5). Iatrogenic causes of intoxication were common and included increased daily dosage and intravenous loading in the emergency room for single seizures in patients with subtherapeutic serum phenytoin levels. The most frequent neurologic findings were nystagmus (95%), ataxia (88%), lethargy (22%), and seizures (19%). Outcome was usually good, but three patients had serious complications. PMID- 1925721 TI - Pregnancy termination because of chromosomal abnormalities: a study of 26,950 amniocenteses in the southeast. AB - A regional study was done to investigate the outcome of chromosomally abnormal pregnancies with respect to the parental decision to continue or to terminate the pregnancy. Fourteen medical centers in the southeastern United States contributed data on 26,950 amniocenteses. In 416 cases (1.54%), cytogenetic abnormalities were reported. Of 378 singleton pregnancies in which a cytogenetic abnormality was reported and for which information regarding pregnancy outcome was available, the decision to terminate the pregnancy was made in 276 (73.02%). When the chromosomal abnormality was autosomal in nature, 240 of the 293 pregnancies (81.91%) were terminated, as compared to 36 of the 85 pregnancies (42.35%) affected with a sex chromosomal abnormality. Pregnancies involving the most common autosomal trisomies (21, 18, and 13) were terminated at a rate of 92% to 95%. No significant difference in the rate of abnormality or in the rate of pregnancy termination existed between the 14 centers. Our findings reflect the largest series of amniocentesis results collected to date. PMID- 1925722 TI - Erythromycin ototoxicity: a call to heighten recognition. AB - Bilateral sensorineural hearing loss developed in a 64-year-old woman treated with intravenous erythromycin lactobionate for bacteremic pneumococcal pneumonia. Discontinuance of the antibiotic led to prompt correction of the hearing deficit. Reversible hearing loss is an infrequently described adverse effect attributed to high-dose erythromycin therapy. Possible risk factors, including age, gender, and hepatic and renal function, may contribute to the development of erythromycin ototoxicity. PMID- 1925723 TI - Rhodococcus equi causing human pulmonary infection: review of 29 cases. AB - Rhodococcus equi is a gram-positive pleomorphic bacillus that has been identified as a life-threatening pulmonary pathogen in the immunocompromised host. Infection with R equi may go unrecognized by physicians unacquainted with its presentation and unaware of the organism's ability to mimic diphtheroids and to stain weakly positive with an acid-fast stain. PMID- 1925724 TI - Pheochromocytoma: diagnosis by scintigraphy using iodine 131 metaiodobenzylguanidine. AB - We summarize our experience using iodine 131 metaiodobenzylguanidine (131I MIBG) imaging in 24 patients with suspected pheochromocytoma and compare 131I MIBG imaging with other imaging modalities such as computerized tomography and magnetic resonance imaging. Our results confirm the high sensitivity and excellent specificity reported from other centers experienced in 131I MIBG imaging. This radiopharmaceutical permits noninvasive, safe, accurate detection of pheochromocytomas of all types. Iodine 131 MIBG scintigraphy is especially efficacious in the detection of extra-adrenal, recurrent, and metastatic tumors. We review precautions in the screening of patients for 131I MIBG examination, imaging techniques, and drugs that interfere with tumor uptake of 131I MIBG. Though 131I MIBG imaging has some limitations, it deserves strong consideration whenever the diagnosis of pheochromocytoma is suspected. PMID- 1925725 TI - Null cell adenoma of the pituitary gland. PMID- 1925726 TI - Clomipramine for obsessive-compulsive disorder: prescribing guidelines. AB - Clomipramine is a newly marketed tricyclic antidepressant drug prescribed for obsessive-compulsive disorder (OCD). It selectively blocks neuronal uptake of serotonin. Clomipramine has been prescribed in Europe and Canada for 20 years in management of depression. Studies have now shown clomipramine to be effective in treating OCD. Dry mouth, visual disturbances, constipation, sexual dysfunction, somnolence, tremors, and dizziness are among the commonly reported side effects. Like other tricyclics, clomipramine exhibits a potential for cardiotoxicity, especially by impairing conduction and/or orthostasis. It also has the effect of lowering seizure threshold. Overdose risk is considerable. Careful medical supervision and adherence to prescribing guidelines are presumed to reduce medication risk factors. The outstanding benefit of this drug is its proved efficacy in the management of obsessive-compulsive disorder, as the first pharmacotherapy approved for this previously rather treatment-resistant condition. PMID- 1925727 TI - Lymphangiomyomatosis: hormonal implications in etiology and therapy. AB - When a 34-year-old woman had dyspnea and chylothorax 8 months postpartum, lymphangiomyomatosis was diagnosed by open-lung biopsy. Baseline laboratory studies to evaluate infertility had revealed normal hormonal levels. She was subsequently treated with various hormones to aid in conception and in sustaining pregnancy. Her condition has improved with progesterone therapy. This case raises concern about the possible adverse consequences of hormonal manipulation in treating infertility. The need for open-lung biopsy in patients with classic manifestations of LAM is also questioned, especially with the advent of high resolution CT scanning, the nonspecificity of hormonal receptors with regard to response to therapy, and the possible need for subsequent lung transplantation. PMID- 1925728 TI - Central and peripheral nervous system demyelination after infection with Mycoplasma pneumonia: evidence of an autoimmune process. AB - We have reported a unique case of multiple central and peripheral nervous system abnormalities after a serologically documented infection due to Mycoplasma pneumoniae. The evidence suggests that this organism is capable of causing demyelination, probably through an autoimmune process. This case may help to provide further insight into the pathogenetic mechanisms involved in other demyelinating diseases in which the triggering exogenous agent is unknown. Certainly this case demonstrated that both central and peripheral nervous system demyelination can occur and that patients with M pneumoniae infections should be observed closely for possible development of neurologic symptoms. PMID- 1925729 TI - Multiple epiphyseal dysplasia misdiagnosed as bioinactive growth hormone disorder. AB - We have reported a case of multiple epiphyseal dysplasia (MED) that was misdiagnosed for many years as bioinactive growth hormone disorder. The condition was misdiagnosed because of its rarity and the physicians' lack of familiarity with it. MED should be considered in the differential diagnosis of a child with short stature and delayed growth. Close follow-up of a patient receiving growth hormone is necessary. PMID- 1925730 TI - Life-threatening complications of empiric ceftriaxone therapy for 'seronegative Lyme disease'. AB - Lyme disease, now the most common tick-borne illness in the United States, has recently received much media attention, due in part to its potentially serious sequelae in untreated patients. Because a rare patient with late illness may lack antibodies to the etiologic agent, Borrelia burgdorferi, physicians may be tempted to give empiric antibiotics for illnesses that may not be Lyme disease. We have described a patient who, despite negative laboratory evidence for late Lyme disease, was treated for 3 weeks with intravenous ceftriaxone and sustained serious complications, including granulocytopenia, fever, hepatitis, and Clostridium difficile-associated diarrhea. We caution physicians to weight carefully the risks of empiric treatment for ill-defined medical problems, and to recognize the hazards of even "safe" medications. PMID- 1925731 TI - Hypokalemic adrenal crisis in a patient with AIDS. AB - Electrolyte disorders have been reported frequently in patients with AIDS. Adrenal insufficiency has been associated with hyponatremia in this group of patients. We have presented the case of a patient with AIDS whose early course was complicated by hyponatremia, hypoglycemia, and hyperkalemia. Shortly thereafter, hypokalemia developed due to gastrointestinal potassium losses from diarrhea. Although cosyntropin stimulation testing later confirmed the diagnosis of adrenal insufficiency, it was not considered because of coexistent hypokalemia. Diarrhea in patients with AIDS and diminished adrenal reserve may invalidate hypokalemia as an exclusion criterion for the diagnosis of adrenal crisis. PMID- 1925732 TI - Trichorhinophalangeal syndrome. AB - Trichorhinophalangeal syndrome type 1 is an autosomal dominant variety of peripheral dysostosis. I have reviewed nine cases of this syndrome and have described two of these cases. I have also presented an extensive review of the literature. PMID- 1925733 TI - Naproxen-associated nightmares. AB - We have reported what we believe to be the first case of naproxen-associated nightmares. Our brief review of basic sleep physiology and the several questions we have raised might help explain this seemingly unusual adverse effect of naproxen. PMID- 1925734 TI - Swallowing-induced atrioventricular block. AB - One of the rare causes of syncope is "swallowing syncope," or "deglutition syncope." We have reported a case of atrioventricular block induced by swallowing. PMID- 1925735 TI - Treatment of tularemia with imipenem/cilastatin sodium. AB - A seriously ill patient with circulatory collapse, fever, acute renal failure, and progressive respiratory failure had dramatic improvement after treatment with imipenem/cilastatin sodium. During the treatment period, a diagnosis of tularemia was established serologically. This case suggests the efficacy of imipenem/cilastatin in the treatment of tularemia. PMID- 1925736 TI - AIDS-related lymphoma diagnosed by flow cytometry of a pleural effusion. AB - We have presented a case in which flow cytometry of pleural fluid was applied in the diagnosis of an AIDS-related lymphoma. Flow cytometric evaluation of malignant effusions is a less invasive means of diagnosing these neoplasms than tissue biopsy. PMID- 1925737 TI - Complete colonic obstruction caused by a sigmoid colon cancer incarcerated in an inguinal hernia sac. AB - An 85-year-old man with a clinical and x-ray picture consistent with a large bowel obstruction had a large left inguinal hernia with an incarcerated loop of sigmoid colon containing a small annular constricting colon carcinoma. Colonic obstruction due to inguinal hernia alone is so rare that a thorough evaluation should be done preoperatively in any patient believed to have colonic obstruction due to inguinal hernia. PMID- 1925738 TI - Hunting accidents. PMID- 1925740 TI - Merkel's cell carcinoma. PMID- 1925739 TI - X-ray ownership. PMID- 1925741 TI - Complications of fusion to the upper cervical spine. AB - Forty-seven operations for posterior fusion of the upper cervical spine were reviewed for complications. Alarmingly, only 11 patients had an entirely uncomplicated course. Most complications were minor, but there were four nonunions, one requiring reoperation. Although seven patients had increased neurologic deficits after surgery, only one was permanent. There was one death due to technical error. Patients with significant instability, myelopathy, prior failed fusions, or unreducible dislocations are at high risk for perioperative neurologic complications. PMID- 1925742 TI - Os odontoideum with posterior atlantoaxial instability. AB - Nine patients who had os odontoideum with posterior atlantoaxial instability are reviewed. Three parameters were measured on the lateral radiographs: the distance from the os odontoideum to the spinous process of the axis in extension (Dext), the distance from the os odontoideum to the posterior arch of the atlas (Datl), and the degree of instability (Inst). Patients were classified into four groups: Group I, local symptoms (N = 3); Group II, transient myelopathy (N = 0); Group III, progressive myelopathy (N = 6); and Group IV, cerebral symptoms (N = 0). The development of cervical myelopathy was not related to degree of instability but to distance from the os to the spinous process of the axis (Dext). Dext was more than 16 mm in Group I and less than or equal to 16 mm in Group III. Five of six patients in Group III underwent myelography. Based on myelographic findings, Group III was further subdivided into two groups, Group IIIA (N = 2) and Group IIIB (N = 3), according to the following characteristics: In Group IIIA, the distance from the os to the posterior arch of the atlas was more than 13 mm, and the spinal cord was impinged between the os odontoideum and the lamina of the axis in extension and reduced in flexion. In Group IIIB, Datl was less than or equal to 13 mm, and the spinal cord was compressed at the level of the atlas during flexion and extension. Stenotic Datl of 13 mm or less specifically defined severe cervical myelopathy. Surgical treatment for cervical myelopathy in os odontoideum with posterior instability is suggested as follows: in the absence of canal stenosis of the atlas (Group IIIA), atlantoaxial fusion in a reduced position is indicated; when associated with canal stenosis of the atlas (Group IIIB), laminectomy of the atlas followed by occiput-to-C2 arthrodesis is indispensable. PMID- 1925743 TI - Whiplash, postural control, and the inner ear. AB - Many patients with "whiplash syndrome" experience unrelenting neck stiffness and pain. This abnormal muscular tension is postulated to be causally related to a central disorder of postural control, which has evolved secondary to injury of the inner ear labyrinthine structures. Moving platform posturography was used to demonstrate the presence or absence of a static or dynamic equilibrium disorder in 48 patients who had experienced the oscillation forces induced by a rear-end automobile collision. Other vestibular tests were used to document dysfunction of the semicircular canals and the otolith structures. A high percentage of patients were found to have faulty inner ear functioning leading to inefficient muscular control of balance and erect posture. Active perilymph fistulas were identified at surgery in seven patients. PMID- 1925744 TI - Magnetic resonance artifact in the postoperative cervical spine. A potential pitfall. AB - An magnetic resonance imaging artifact that stimulates hypertrophic bone formation is described in patients who have had an anterior cervical discectomy. The magnetic resonance images of 26 patients with anterior cervical discectomy were retrospectively reviewed. Comparison was made to the available concurrent computed tomographic scans, computed tomographic myelograms, and operative reports. A bovine spine was drilled with a drill only at one level and with a metal suction tip in close proximity to the drill at another level, and magnetic resonance images were obtained. Artifact was present in 12 patients and absent in 14; this was confirmed in the 8 patients with comparison studies. Close correlation was seen with the prospective reading of the presence of artifact and operative drill use in the seven patients with available operative reports. The bovine spine model showed no artifact at the drill-only level and significant artifact at the level where the metal suction tip was positioned next to the drill. Small metal flecks were seen grossly at the second level, but not on plain roentgenograms. The metallic magnetic resonance artifact seen in postoperative cervical spines is probably from small bits of metal from the metal suction tip as it occasionally hits the drill. Bone abnormalities seen on magnetic resonance imaging at the level of a previous anterior cervical discectomy may need a cervical computed tomogram to confirm the findings. PMID- 1925745 TI - The use of freeze-dried allograft bone for anterior cervical fusions. AB - A consecutive series of 87 patients undergoing Smith-Robinson anterior cervical fusion were analyzed. Either freeze-dried tricortical iliac crest bone or tricortical autograft bone was used. Surgical technique was otherwise identical. Radiography showed delayed union at 3 months in 13% of patients with autograft and in 37% of patients with freeze-dried allograft. At 1 year, radiography showed nonunion in 8% of patients with autograft and in 22% of patients with allograft. One-level procedures had a delayed union rate of 7% for autograft and 21% for allograft. Nonunion in one-level procedures was 5% for both autograft and allograft. For two-level procedures, the nonunion rate was 17% for autograft and 63% for allograft. Graft collapse was more commonly seen with freeze-dried allograft (30%) than with autograft (5%). Relief of neck and arm pain, however, was similar in both groups. PMID- 1925746 TI - Somatosensory-evoked and dermatomal-evoked potentials are not clinically useful in the prognostication of acute spinal cord injury. AB - This study examined the ability of somatosensory-evoked and dermatomal-evoked potentials to predict motor return after acute spinal cord injury. Fifty-seven of 102 patients who were studied with somatosensory-evoked potentials and dermatomal evoked potentials were followed for more than 1 year, and their initial electrophysiologic studies were correlated with motor improvement. No patient with a complete spinal cord injury on initial physical evaluation ever developed motor return. An initial examination demonstrating incomplete spinal cord injury heralded a result of walking or better in 56.4% of incomplete patients with spinal cord injury. Both the initial physical examination and evoked potentials were reasonable predictors of further motor improvement. However, evoked potentials added little or no useful prognostic information to the initial physical examination in either complete or incomplete spinal cord injury patient groups. PMID- 1925747 TI - Percutaneous computed-tomography-guided biopsy of the thoracic and lumbar spine. AB - Axial computed tomographic scans were used to guide percutaneous needle biopsies in 76 patients with thoracic and lumbar spinal lesions. Prebiopsy evaluation included spine radiographs, radionuclide bone scans, computed tomographic scans, magnetic resonance imaging scans in some cases, and coagulation studies. Forty five patients were diagnosed as having metastatic lesions, 11 infection, and 12 primary bone tumors. Of all patients, 34 had lytic vertebral lesions with significant collapse and questionable spinal stability. Six of those had a concomitant paravertebral mass. A clinical and pathologic correlation was completed for each of the cases studied. Histologic diagnosis confirming the clinical suspicion was obtained on the first biopsy attempt in 65 (86%) of the 76 cases. PMID- 1925748 TI - Intraspinal synovial cysts. Magnetic resonance evaluation. AB - Five intraspinal synovial cysts in four patients were evaluated with noncontrast magnetic resonance imaging and magnetic resonance imaging with the contrast agent gadolinium diethylenetriaminepentaacetic acid. Useful findings included demonstration of both solid and cystic components, early enhancement of the solid component and cyst periphery, delayed enhancement of the cyst, persistent enhancement of the solid component and cyst capsule, enhancement of the apophyseal joint, and recognition of a possible connection between the cyst and apophyseal joint. Although computed tomographic findings of synovial cysts are quite characteristic for the diagnosis in most cases, contrast magnetic resonance imaging may provide additional information for a more definitive diagnosis. PMID- 1925749 TI - Aspergillus osteomyelitis of the spine. AB - Aspergillosis involving either the vertebral body or the intervertebral disc is a rare cause of osteomyelitis of the spine. The following is a report of five cases of Aspergillus fumigatus infection of the spine treated successfully with amphotericin B and 5-flucytosine. In three patients, the diagnosis was established at closed-needle biopsy; two patients with paraplegia had an anterior decompression and fusion. The follow-up period ranged from 19 to 48 months. PMID- 1925750 TI - Plantar weight-bearing pattern in idiopathic scoliosis. AB - Eighty-four patients were objectively evaluated with a weight-bearing pattern analyzer to determine whether spine deformity has an effect on the amount of weight borne on the right versus left foot and on the fore versus the hind foot. Patients with idiopathic scoliosis treated with bracing and surgery and patients with Scheuermann's kyphosis treated with bracing were compared with control subjects. Patients with right thoracic and thoracolumbar curves did not bear more weight on the right foot, as was previously thought. Patients with relatively unaffected lumbar spines exhibited normal sagittal plane weight-bearing patterns, whereas patients with double major and lumbar curves did show abnormalities in the weight-bearing pattern. Bracing of curves less than 40 degrees did not alter the plantar weight-bearing pattern, but it did significantly alter the pattern in curves greater than 40 degrees. Surgically treated patients were found to have increased hindfoot weight-bearing irrespective of the curve type or surgery. PMID- 1925751 TI - Magnetic resonance imaging of the brain stem in adolescent idiopathic scoliosis. AB - The cause of adolescent idiopathic scoliosis remains an enigma. Several studies have demonstrated abnormalities of posture, proprioception, and equilibrium control in patients with adolescent idiopathic scoliosis. These functions are integrated by structures in and around the brain stem. Twenty-seven patients with adolescent idiopathic scoliosis were studied with magnetic resonance imaging to delineate the anatomy of the brain stem in such patients. Imaging was conducted from the hypothalamus to the spinal cord at C3 in 26 patients; the remaining patient underwent an incomplete study because of a claustrophobic reaction. The study group consisted of 25 females and 2 males with an average age of 16 + 5 years. There were 19 right thoracic curves, 5 thoracolumbar curves, and 3 left lumbar curves. The mean primary curve size was 27 degrees at the most recent clinical evaluation. Seven patients were treated with observation, 14 with bracing, and 6 with surgery. The magnetic resonance imaging studies were read independently by three attending radiologists in a randomized, blinded fashion along with the magnetic resonance imaging studies of 11 controls. Asymmetry in the ventral pons or medulla in the area of the corticospinal tracts was noted in seven study patients and one control; one study patient had an enlarged cisterna magna and one an inconclusive (incomplete) study. These findings may support previous studies that have suggested a central nervous system abnormality as a cause of adolescent idiopathic scoliosis. PMID- 1925752 TI - Lumbosacral kyphosis, tethered cord, and diplomyelia. A unique spinal dysraphic condition. AB - Four patients are described with a triad of neuroectodermal abnormalities consisting of lumbosacral kyphosis, tethered cord, and dyplomyelia. Of utmost importance is the recognition of the association between this type of kyphosis and the underlying spinal cord pathology and the progressive nature of the deformity. The patient presenting with lumbosacral kyphos and the presence of sacral hypoplasia should have a neuroradiographic evaluation (magnetic resonance imaging scanning or enhanced computed tomography) to rule out the presence of a tethered cord or other neural abnormalities. Early surgical intervention for release of the tether and fusion should be carried out to prevent neurologic deterioration and curve progression. PMID- 1925753 TI - Coronal decompensation produced by Cotrel-Dubousset "derotation" maneuver for idiopathic right thoracic scoliosis. AB - From 1985 to 1987, 82 patients with idiopathic scoliosis followed 12 to 44 months underwent selective fusion and correction of their right thoracic curves by Cotrel-Dubousset instrumentation using the "derotation" maneuver. Preoperative, postoperative, and follow-up standing anteroposterior roentgenograms of the spine were analyzed. For curves in which there was deviation from the midline (plumb line) and rotation of the lumbar segments, an increased incidence of decompensation was produced after surgery, when posterior Cotrel-Dubousset instrumentation and fusion were carried to the "stable" vertebra with one rod bend and hook alignment on the left sided derotation rod. Previous guidelines established for selective fusion with conventional posterior instrumentation (Harrington or Luque rods) may not be applicable to derotation with Cotrel Dubousset instrumentation. PMID- 1925754 TI - Results of lumbar hemivertebral excision for congenital scoliosis. AB - The purposes of this study were to determine the long-term correction achieved by excision of lumbar hemivertebrae and the risk attendant. Seven patients had a follow-up of 41.14 months for lumbar hemivertebral excisions. Six had two-stage anterior vertebral body excision and, 7-8 days later, posterior lamina and pedicle excision with fusion. One patient had a single-stage correction. After surgery, the patients were in pantaloon casts or braces for a minimum of 6 months (supine, first 6-12 weeks). Hemivertebrae were at L2 (N = 1), L3 (N = 1), L4-L5 (N = 1), and L5-S1 (N = 4). Preoperative curves or hemivertebral angles averaged 36.6 degrees (range, 30-52 degrees). Average age was 7.5 years (range, 22 months to 12.5 years). Mean follow-up was 41.14 months. Surgical correction of the seven cases averaged 28.0 degrees. Two-stage procedures yielded 29.7 degrees correction with no complications; single-stage yielded 18 degrees correction, and the only complication was an L5 nerve root paresis. PMID- 1925755 TI - The attachments of the lumbar erector spinae. AB - The attachments and orientation of every fascicle of the lumbar erector spinae were determined in five cadavers and recorded radiographically. Little variation was found in the sites of muscle attachment, which enabled the construction of maps whereby these sites could be plotted on clinical radiographs or models of the lumbar spine. When all fascicles were plotted on 21 clinical radiographs using the maps previously developed, no significant difference in the orientation of fascicles was found compared with that observed in cadavers. This result vindicates the technique used to plot the location of individual fascicles of the lumbar back muscles. PMID- 1925756 TI - The intersegmental and multisegmental muscles of the lumbar spine. A biomechanical model comparing lateral stabilizing potential. AB - The intersegmental and multisegmental musculature of the lumbar spine was studied in a biomechanical model to compare their lateral stabilizing potential. By approximating the active and passive behavior of the stretch reflex as a variable stiffness spring whose stiffness was proportional to activation, the critical muscle stiffness required for mechanical stability was calculated. The model demonstrated that the intersegmental muscles were the least efficient at laterally stabilizing the spine. At any given load, multisegmental muscles were more efficient, and their efficiency increased with the number of segments spanned. The most efficient muscles were those that originated from the pelvis, spanning the maximum number of segments. The muscular model was unstable, regardless of the muscular stiffness, when any vertebral segment was devoid of muscle. Moreover, when the load on the spine is increased, buckling can be prevented most efficiently with the pelvic muscles and least efficiently with the intersegmental muscles. PMID- 1925757 TI - A new robust index for measuring isokinetic trunk flexion and extension. Outcome from a regional study. AB - The purpose of this study was 1) to provide normative data for isokinetic trunk strength as measured by peak torque, best work repetition, and a new composite variable, "muscle performance index"; and 2) to examine the effects of protocol velocity, subject age, gender, height, and weight on these measurements. A significant decrease in peak torque of extension for females (P less than 0.0001) was seen as protocol velocity increased, but no differences were seen in males. A statistically significant amount (0.5-0.7) of the variance in isokinetic measurements was explained by subject age, height, and weight. Multivariant analysis of covariance showed the effects of these variances to be significant on all measurements except for the muscle performance index, which was unaffected by protocol velocity and remained stable without adjustments for subject age, weight, or height. PMID- 1925758 TI - Kinetic potential of the lumbar trunk musculature about three orthogonal orthopaedic axes in extreme postures. AB - Many studies have examined the mechanics of the lumbar spine in various planes, but only a limited number of three-dimensional investigations have been reported. Analysis of the low back during complex, dynamic postures demands rigorous representation of the trunk musculature. The data of this study demonstrated the force and torque contributions of approximately 50 laminas of various trunk muscles to flexion-extension, lateral bending, and axial twisting torque at the L4-L5 joint. This analysis was conducted with the spine in an upright standing posture and when fully flexed (60 degrees), laterally bent (25 degrees), and axially twisted (10 degrees) together with two examples of combined postures. Maximum moment potential, muscle length excursions, and the resultant compressive, anteroposterior shear, and lateral shear forces on the joint were also computed. The results indicate that the position of the vertebrae and their orthopaedic axes, which are a function of spinal posture, are an important factor in the reasonable determination of joint compressive, lateral shear, and anteroposterior shear loads. Muscle length changes that exceeded 20% of their respective length during upright standing were not observed during a full axial twist, but were observed in portions of the abdominal obliques during lateral bending, and in some extensors during full flexion. Extreme postures tended to change the torque potential of some muscles and influence joint load. Various portions of erector spinae were observed to have appreciable potential to generate torque about all three orthopaedic axes. This observation supports the notion held by some therapists that conditioning of the erector spinae is of utmost importance. PMID- 1925759 TI - Radiographic and histologic effects of chondroitinase ABC on normal canine lumbar intervertebral disc. AB - Twelve dogs were divided into two equal groups and given lumbar intradiscal injections of 10, 50, or 100 U/ml of chondroitinase ABC reconstituted in sodium acetate buffer. Radiographs of the lumbar spine were made before and after surgery in both groups. Additional films were made at 5 days after surgery in Group I and at 7, 14, and 21 days after surgery in Group II. All spaces injected with 50 or 100 U/ml chondroitinase ABC demonstrated significant radiographic narrowing in both groups compared with uninjected control and buffer injected discs (P less than 0.001). Discs injected with 10 U/ml of chondroitinase ABC showed increased narrowing over time from 7 to 21 days (P less than 0.05). A zone of safranin O depletion was present in the ventral anulus fibrosus adjacent to the nucleus pulposus in all treated discs, indicating proteoglycan loss. All histologic effects of chondroitinase ABC were confined to intervertebral disc tissues. Chondroitinase ABC appears to be effective for chemonucleolysis in dogs. PMID- 1925760 TI - Viscous carboxymethylcellulose in the prevention of epidural scar formation. AB - Six chemical agents were evaluated for their efficacy in preventing epidural scar formation following laminectomy in rabbits. One agent was carboxymethylcellulose and the other five agents represented various compositions of modified carboxymethylcellulose. Four weeks after laminectomy, spines were harvested and decalcified, and transverse sections were prepared for histologic analysis. Subjective evaluation suggested that two agents appeared to inhibit epidural scar formation compared with the untreated controls. Objective evaluation was performed by quantitating scar tissue area at the laminectomy site with a digitizing tablet. In agreement with the subjective evaluation, two agents were found to have significantly reduced epidural scar tissue area compared with the control (control = 0.418 +/- 0.16 SE mm2vs. Agent 2 = 0.067 +/- 0.02 [P less than 0.05] and Agent 5 = 0.089 +/- 0.02 [P less than 0.05]). Of the remaining four agents, one of which was the unmodified carboxymethylcellulose, none showed significant reduction in scar tissue formation. These findings indicate that viscous preparations of modified carboxymethylcellulose can act as a barrier against epidural scar formation following laminectomy. PMID- 1925761 TI - Dural compression as a cause of paraplegia during operative correction of cervical kyphosis in ankylosing spondylitis. PMID- 1925762 TI - Iatrogenic spondylolysis complicating distal laminar hook placement. A report of two cases. PMID- 1925763 TI - Dissociation of neurogenic motor and somatosensory evoked potentials. A case report. PMID- 1925764 TI - A multicenter analysis of percutaneous discectomy. PMID- 1925766 TI - [Dehiscence and fenestration: study of distribution and incidence in a homogeneous population model]. AB - Ninety crania of Italian and Austrian males, 25-32 years old, coming from the ossurary of Custoza have been examined, (in all 2205 teeth) to determinate the presence and the frequency of dehiscences and fenestrations. All the crania presenting signs of serious stomatologic pathology have been rejected. Dehiscences are more frequent than fenestrations (7.30% vs 6.98%); dehiscences are more frequent in the mandible than in the maxilla (11.55% vs 1.86%), while fenestrations are more frequent in the upper alveolar arch than in the lower one (13.23% vs 2.10%); the upper right first molar is resulted to be the tooth showing the greatest number of defects (8.13% dehiscences and 49.69% fenestrations). PMID- 1925765 TI - [Autotransplantation of an impacted supernumerary tooth]. AB - The Authors report on a case of interesting tooth transplantation using a supernumerary in the site of a lower premolar root affected by periapical granuloma. Irrespective of local unfavourable conditions, the good result of surgical operation is demonstrated by up to now vitality and stability of transplanted tooth. PMID- 1925767 TI - [Radiodiagnostic evaluation in osseointegrated dental implants]. AB - The Authors examine the various radiological techniques indispensable to pre- and postsurgical evaluation in endosseous dental implantology. Of each technique the choice criteria and diagnostic potentialities are suggested. PMID- 1925768 TI - [Adamantinoma from odontogenic cysts]. AB - The observation of an adamantinoma's case propped up an odontogenic cyst to check the complicated histogenic problem connected to this eventuality. After considering several theories they suppose a probable derivation from the odontogenic epithelium that has undoubted potentiality. PMID- 1925769 TI - [Ectopic salivary tissue in the mandibular region]. AB - The presence of salivary tissue into the mandible represents often the submaxillary gland dislocation into the maxillary bones. Together with a literature revision, we have analysed the histogenetic hypothesis of this eterotopia and its prognostic implication. At last it has been described a clinical case treated in our Institute. PMID- 1925770 TI - [Lateral periodontal cysts]. PMID- 1925771 TI - [S.E.M. analysis of composite resin surfaces applied to chemically and chemo mechanically treated dentin]. AB - The authors evaluated, at scanning electron microscope (S.E.M.), the morphological aspects of composite resin surfaces applied on dentin subjected, "in vitro", to chemical or chemo-mechanical treatments. S.E.M. photographs of dentinal surfaces of composite, applied on dentin treated with acid agents or Caridex, showed extensive penetration of resin tags into dentinal tubules and their deep adaptation to rough and winding dentinal surfaces. The obtained results have been evaluated in the light of recent advances in biocompatibility and long-term stability of composite fillings, in particular, to setting up new materials and methods in cavities preparation and treatment. PMID- 1925772 TI - [Esthetic treatment of discolored nonvital teeth]. PMID- 1925773 TI - [Present status of care of pediatric injuries in the Czech Republic]. AB - The great majority of child injuries are treated at the outpatient department and only in case of serious injury the child is admitted to hospital. In addition to the absolute number of injuries in our Republic it is also important to know how child injuries are treated, i. e. by whom, what are the material conditions for treatment in different departments and what is the standard of treatment. In an attempt to answer at least partly some of these questions the author sent questionnaires to 82 surgical and orthopaedic departments. Replies were obtained from 65 departments (80% of those addressed). From the answers ensued lack of uniform care of child injuries in out-patients' as well as in-hospital care. The majority of child injuries is treated by general surgeons (some 80%) and children with injuries are hospitalized in surgical, orthopaedic and paediatric departments. PMID- 1925774 TI - [Hemophilia from the viewpoint of the neurosurgeon]. AB - The authors describe a case of cerebral haemorrhage associated with haemophilia A -their own observation, findings and confrontation with data in the literature. They draw attention to the rare incidence of the above complication, discuss the site of haemorrhage and possibilities of treatment. PMID- 1925776 TI - [General guidelines for collection and transportation of materials intended for bacteriological examination]. PMID- 1925775 TI - [Parenteral nutrition in neonates after surgery of congenital developmental defects]. AB - The authors discuss the problem of administration and amount of fluids and electrolytes in neonates after operations of inborn developmental defects and during the postoperative period. Parenteral nutrition is considered by the authors an important component of comprehensive intensive care which influences in a marked way the results of the surgical operation. As regards the control of water homeostasis they analyze factors which control the hydration. Next the authors discuss the daily intake of ions; some space is devoted to sodium the main cation of extracellular fluid. Next the authors discuss this aspect of parenteral nutrition as practiced at the Clinic for Paediatric Surgery in Brno. PMID- 1925777 TI - [Aneurysms of the renal artery in childhood]. AB - The authors describe the case-history of a nine-year-old boy engaged in sports, suffering from serious hypertension due to an aneurysm of the renal artery of the right kidney. Vascular reconstruction was performed. They boy died, however, suddenly 20 hours after operation and on necropsy serious hypoplasia of the adrenals was revealed. PMID- 1925778 TI - [Spontaneous perforation of the stomach in neonates]. AB - The authors report on five neonates with perforation of the stomach manifested during the first two weeks of life. Four of the neonates had low birth weights. Asphyxia was proved in three neonates, in two histological examination revealed a congenital defect of the musculature of the gastric wall, in three a nasogastric tube was used. Causes which lead to gastric perforation in neonates are not uniform. Only by early diagnosis and surgical treatment the mortality can be reduced. PMID- 1925780 TI - [Personal experience with surgical treatment of vesicorenal reflux--indications and surgical technic]. AB - The author evaluates his experience with the surgical treatment of vesicorenal reflux in a group of 171 children 42 boys and 129 girls. Depending on the degree of reflux, he operated 12 children by the technique of Gil Vernet, 46 according to Politano-Leadbetter and 112 according to Anderson-Glenn. This technique proved useful and he achieved excellent results. PMID- 1925779 TI - [A rare cause of hemorrhage into the upper gastrointestinal tract in children]. AB - The authors deals in the introduction with the problem of haemorrhage into the GIT in children. He describes the case of a 12-year-old boy where originally intermittent mild haematemesis developed after 30 hours into profuse haemorrhage and called for urgent surgical intervention. Severe oesophagorrhagia of arterial origin revealed on operation was arrested by means of a Sengstaken tube and the haemorrhagic shock was checked by transfusions of 4.5 1blood. For three days the was transferred with regard to the finding and permanent treatment of the source of haemorrhage to clinical department. There, however, on the eighth day after development of haematemesis he died during thoracotomy. Haemorrhage into the stomach and gut was involved from a pseudoaneurysm of the thoracic aorta which developed in a scar after resection of its coarctation and perforated after five years into the upper oesophagus. In the conclusion the author describes the cause of development of aortodigestive fistulae, diagnostic and therapeutic difficulties of their solution and possible intervention. PMID- 1925781 TI - [Diagnostic value of the rectal examination and the difference in axillo-rectal temperatures in acute appendicitis in childhood]. AB - The authors deal with the importance of pain in the Douglas space during rectal examination and the contribution of the axillo- rectal difference in temperature in the diagnosis of acute appendicitis in a group of 402 children operated on who had the above preoperative diagnosis. Marked pain in the Douglas space was recorded in 53.6% children and complete absence of pain in 31.2% of the children with acute appendicitis proved at operation. In children where so-called negative laparotomy was performed this ratio was reversed. When evaluating the axillo rectal difference in temperature the authors reached the paradoxical conclusion that an obviously physiological difference in the axillo-rectal temperature (up to 0.5 degrees C) was slightly more frequent in acute appendicitis than in negative laparotomy. An obviously pathological difference (1 degrees C or more) was three times more frequent in patients with negative laparotomies than in acute appendicitis. Next the authors discuss views reported in the literature where data on the asset of rectal examination in acute appendicitis vary between 2.9-73%. In the conclusion the authors recommend rectal examinations in all children with suspicion of any type of acute abdomen, however, taking into account that pain in the Douglas space will contribute only little to the reduction of the number of negative laparotomies. They consider assessment of the axillo-rectal difference in temperature practically useless. PMID- 1925782 TI - [Indications for surgical treatment of varicocele in the prepubertal age]. AB - The author discusses the pathophysiology of infertility caused by varicocele and mentions experience reported in the literature. The author himself treated 16 boys of prepubertal age and considers early operation of varicocele during prepubertal age indicated. PMID- 1925783 TI - [Results of surgical treatment of aortic coarctation]. AB - The authors summarize the results of surgical treatment of coarctation of the aorta in 98 patients. Te group comprised 70 children aged 3 to 15 years and 28 adults. The most frequently used technique was resection of the coarctation with a direct end-to-end anastomosis. It was used in a total of 83 patients. Three patients died, i. e. 3.1%. Of 32 patients who were invited for a check-up examination 16 came. Three of them had undergone a plastic operation with a dacron patch. All were subjected to angiographic examination in a lateral projection by injection of the contrast substance into the aortal arch and pressure readings were taken in the aorta above and below the site of anastomosis. Residual gradients were found in three patients (10, 12, 20 torr). Hypertension persists in 6 patients. In four patients slight stenosis of the aorta was found without a gradient, in one patient a small pseudoaneurysm. None of the findings called for further surgical intervention. PMID- 1925784 TI - [Air gun injuries in children]. AB - The authors describe four cases of air rifle child injuries. One was a potentially lethal injury, a penetrating wound of the transverse colon and injury to the stomach. During urgent laparotomy the perforations of the gastrointestinal tract were sutured. In the remaining three children the injuries were less serious and affected soft tissues. In the discussion the authors summarize data from the literature concerning injuries to the head, neck, chest, abdomen and extremities, incl. lethal injuries. In instances when a penetrating abdominal injury cannot be ruled out, the authors emphasize the necessity of urgent laparotomy and surgical treatment of possible intraabdominal lesions. In injuries to other parts of the body a strictly individual procedure focused on repair of the injury is indicated. The authors also emphasize prevention of these injuries by adherence to safety during shooting and other manipulations with arms an air rifle must not be a toy for children and adolescents unless they are supervised by a responsible adult. PMID- 1925785 TI - [Parenteral nutrition in multiple injuries. III]. AB - One of the main features of parenteral nutrition in patients with multiple injuries remains the slow administration of different substances and the adherence to "anti-insulin provisions" which are usually called for during the first week after the injury. The recommended ratio of amino acids with branched carbon chains for patients with multiple injuries (i. e. 40-50% from the total amino acids) is administered from the onset of infusion therapy, frequently already during operation. With this aspect in mind the model pattern of parenteral nutrition was elaborated. PMID- 1925786 TI - [In vitro comparison of properties of aortic allotransplants and the Bjork-Shiley valve]. AB - The authors performed an in vitro test and compared some hydrodynamic parameters of Bjork Shiley valves and aortic allotransplants. Both types of valves are comparable from the aspects of most parameters. The Bjork Shiley valve gives some better values with the exception of sufficiency. The great scatter of assessed values in biological valves draws attention to the necessity to make the test before implantation. From the hydrodynamic aspect the authors consider allotransplants valvular prostheses suitable for implantation. Ref. 5, Tab. 1. PMID- 1925787 TI - [Adrenal tumors and surgical approaches to the adrenal glands]. AB - In 1987 at the First Surgical Clinic in Bratislava four patients with adrenal tumours were operated. Hormonally inactive tumours are, however, diagnosed late on account of their latent growth. To the diagnosis of tumours sonography and computed tomography contributed in a major way. Adrenal tumours must be radically removed, sometimes even with surrounding organs (kidney, spleen, pancreas). Malignant tumours have a very adverse prognosis. PMID- 1925788 TI - [Atypical aneurysms of the abdominal aorta]. AB - The authors submit a report on two patients with pseudoaneurysmatic bulging in the subrenal portion of the abdominal aorta. They present detailed histological findings in the two operated patients and discuss the aetiology of these formations. They draw attention on the failure of aortographic examinations in the diagnosis of these formations and the necessity of sonographic or CT examination. During surgery only partial resection of these formations is possible with subsequent reconstruction of the arterial circulation. The long term results of these operations are favourable. PMID- 1925789 TI - [Conn's adenoma as a cause of hypertension]. AB - The authors describe two observations of primary hyperaldosteronism, caused by a cortical adrenal adenoma (Conn's adenoma). Both patients were treated by unilateral adrenalectomy from lumbotomy. (In the second patient subtotal resection). The problem is discussed from the aspect of morphological diagnosis and location with emphasis on the primary importance of CT. The surgical operation is aimed and simple without the necessity of peroperative confirmation of the morphological background of the syndrome. PMID- 1925790 TI - [Life prognosis in patients with prehepatic portal hypertension treated with portosystemic shunts]. AB - The authors present the results of the long-term follow up of nine patients with prehepatic portal hypertension treated by a portosystemic anastomosis. The evaluation was made 5-21 years after operation, according to criteria focused on the therapeutic effect of the anastomosis and its possible pathophysiological sequelae. In the authors' opinion the anastomosis is the operation of choice suited for patients lacking a tendency of normalization of the portal circulation and with dangerous manifestations of portal overpressure. The indication is restricted to early age of the patients (for technical reasons). Conversely the patient should not attain adult age without unresolved hypertension. For correct timing of the operation knowledge of the development of the disease is essential. Primarily infact livers do not undergo pathological changes even after years of hypertension nor several years after an anastomosis. This is consistent with the fact that these patients lack clinical manifestations of portosystemic encephalopathy. Investigations of the course of flow curves during semiquantitative evaluation of hepatobiliary sequential scintigraphy supported the previous view that establishment of the anastomosis and elimination of portal overpressure improves hepatic perfusion. Hepatobiliary sequential scintigraphy not previously used in this indication may be of value in the follow up of the disease and evidence of the anastomosis. This preliminary conclusion is being tested in a prospective study. PMID- 1925791 TI - [A method of tying a surgical knot with one hand which allows the surgeon to maintain tension on the ligature while simultaneously releasing the forceps]. AB - The author describes the preparation of a surgical Knot with one hand, whereby one end of the ligature during ligation of the artery is held by the thumb and index finger and the second one is twisted round the little finger of the same hand in the distal interphalangeal groove. When tightening the knot, simultaneously the forceps is released, using the other hand. PMID- 1925792 TI - [Is treatment of acromioclavicular dislocation with coraco-clavicular cerclage justified?]. AB - The authors analyze the results of treatment of AC luxation by the method of coracoclavicular cerclage at the First Surgical Clinical of the Faculty Hospital and Policlinic in Olomouc in 1968-1988. A total of 18 patients were examined after an average period of 12.5 years following operation. 88.8% of the patients were satisfied with the results of treatment, one patient has permanent complaints and evaluates the result as poor (5.5%), one patient has an indifferent view of the therapeutic results (5.5%). A detailed evaluation of subjective complaints was made as well as of objective findings, X-ray pictures, and the results were compared with data in the literature. In the authors' opinion coraclavicular cerclage has comparable results with other therapeutic methods, and as compared with some, it is more sparing and technically less pretentious. PMID- 1925793 TI - [Heterogeneity of anticardiolipin antibody]. AB - The antibody to cardiolipin(ACA) was tested in patients with systemic rheumatic disease. The frequency of IgG ACA was 46/100(46.0%) in systemic lupus erythematosus(SLE). In other rheumatic disease, this was less than 20%. Significant correlation between the presence of IgG ACA and thrombosis and/or thrombocytopenia was found in patients with SLE. Eight sera containing high titered IgG ACA from lupus patients were selected for further inhibition study. Inhibitors were consisted of cardiolipin(CL), phosphatidyl(p-)serine, p-inositol, p-glycerol, p-ethanolamine, p-choline, ds-DNA, ss-DNA, fresh platelets(PLT)and fresh red blood cells(RBC). All sera were markedly inhibited by negatively charged phospholipids. In 4 sera(group B), there was moderate inhibition by ss DNA, ds-DNA, PLT and RBC. In another 4 sera(group A), mild but significant inhibition was obtained by PLT alone. The number of platelet in group A was less than that in group B. There were some differences in inhibitory activity, suggesting heterogeneity of antibody to CL. It may be possible to speculate that heterogeneity of IgG ACA cause various combination of clinical features such as thrombocytopenia and thrombosis. PMID- 1925794 TI - [Preliminary criteria for the diagnosis of pulmonary hypertension in mixed connective tissue disease]. AB - Based on analysis of data obtained from multicenter patients with collagen diseases (83 with pulmonary hypertension(PH) and 472 without PH), preliminary criteria for the diagnosis of PH in mixed connective tissue disease (MCTD) were proposed by the Research Committee for MCTD of the Ministry of Health and Welfare of Japan. The diagnosis of PH requires four or more out of six clinical and laboratory findings, including exertional dyspnea, systolic pulsation on the left sternum, increased 2nd pulmonary sound, dilatation of the pulmonary artery on chest X-ray, right ventricular hypertrophy on the electrocardiogram, and right ventricular enlargement on the echocardiogram. Alternatively, either an increase of mean pulmonary artery pressure over 25 mmHg measured by right ventricle catheterization, or the corresponding finding on Doppler echocardiography is also valid for the diagnosis of PH. When these criteria were applied to the patients in this study, the sensitivity was 92% and the specificity 100%, showing that PH may be adequately diagnosed using non-invasive methods. The number of criteria satisfied by patients with PH was well correlated with their mean pulmonary artery pressure measured by heart catheterization. PMID- 1925795 TI - [Thermography of collagen diseases with Raynaud's phenomenon]. AB - In forty-four patients with collagen diseases accompanied with Raynaud's phenomenon(systemic lupus erythematosus(SLE)10, progressive systemic sclerosis(PSS)15, primary Sjogren's syndrome(PSJS)18 and mixed connective tissue disease(MCTD)1), we analyzed the thermography of fingers after thermal stimulation with cold water(15 degrees C, 30 seconds). In normal controls, the temperature of the distal points of fingers was higher and recovered more quickly than that of the proximal points(proximal interphalangeal joint; PIP). But in the patients with Raynaud's phenomenon, the temperature of distal point of fingers was lower and recovered more slowly than that of proximal points. Because the difference of the temperature between the distal and the proximal points (DP)is a good parameter to distinguish these two thermographic patterns, we analysed DP. DP is less influenced by room temperature than the temperature of fingers and the recovery temperature after thermal stimulation which have been used as indicators of Raynaud's phenomenon. DP in the normal controls was significantly higher than that in the patients. DP in PSS was lower than that in SLE and PSJS, and statistically associated with the markers of disease activities, such as erythrocyte sedimentation rate, titers of anti-RNP antibody and diffusing capacity of lung. These results show that thermographic pattern and the value of DP are the useful indicator of severity of Raynaud's phenomenon. PMID- 1925796 TI - [Magnetic resonance imaging in neuro-Behcet's disease--comparison with clinical, X-ray CT, and PET findings]. AB - Magnetic resonance imaging (MRI) examinations of 23 patients with neuro-Behcet's disease were evaluated to correlate the results with clinical, X-ray CT, and positron emission tomography (PET) findings. The results were as follows: Focal lesions were detected in 17 (73.9%) and brain atrophy was depicted in 10 (43.4%) out of the 23 patients. This ratio was higher than X-ray CT. The acute phase lesions detected by MRI at the first medical examination were diminished after the treatment in proportion to the improvement of the clinical symptoms. Cerebral blood flow study and glucose metabolism study by PET were performed on patients whose main problems were mental symptoms. Both cerebral blood flow and glucose metabolism were decreased in these patients. These results suggest that MRI is a useful technique for detecting the central nervous system lesions of neuro Behcet's disease and monitoring its clinical status and therapeutic response for this disease, and PET provides a useful way of understanding the haemocirculatory and metabolic aspects of this disease. PMID- 1925797 TI - [A case of pregnant woman with lupus anticoagulant positive systemic lupus erythematosus complicated with intrauterine fetal death, eclampsia, and brainstem vascular damage]. AB - A 28-year-old female patient with SLE was found to have complications from intrauterine fetal death, eclampsia, and brainstem vascular damage during pregnancy. These symptoms were associated with lupus anticoagulant (LAC). An LAC positive SLE case with accompanying cerebrovascular disease and fetal loss at the same time has rarely been reported. The first brain CT scan revealed the presence of multiple middle pons infarction. Ten days after onset, a brain MRI showed the change into hemorrhagic infarction in the same region, suggesting disseminated intravascular coagulation (DIC) caused by severe obstetric complications. Although the severity of the brain damage implied poor prognosis, her symptoms were alleviated by intensive care with a large amount of steroid therapy and active rehabilitation. LAC-positive SLE patients are apt to encounter obstetric complications in pregnancy. Therefore they must be treated by medical specialists in cooperation with gynecologists. When they also have accompanying with cerebrovascular diseases, active therapy for SLE is necessary for a good prognosis. PMID- 1925798 TI - [A case of systemic lupus erythematosus complicated with pulmonary hypertension and massive pericardial effusion]. AB - A 22 year-old-female had suffered from polyarthralgia and Raynaud's phenomenon since 1984. In 1986, she was diagnosed as systemic lupus erythematosus (SLE). In April 1988, she was admitted to Kawasaki Municipal Hospital because of fever and dyspnea on exertion (DOE). Physical examination showed high fever, butterfly rash, oral ulcer and elevation of heart sound IIp on auscultation. Laboratory findings revealed that erythrocyte sedimentation rate was elevated to 105 mm/hr. The following values were observed, anti DNA antibody 391 IU/ml, serum IgA 5mg/dl, anti IgA antibody weakly positive. Chest X ray showed CTR 65%. Echo cardiogram showed massive pericardial effusion. 201T1 myocardial SPECT revealed right ventricular pressure over loading. PSL 40 mg/day was started to administer for the massive pericardial effusion due to SLE activities. On 6th of June, right heart catheterization confirmed the pulmonary hypertension (PPA 22 mmHg, Pulmonary artery resistance (PAR) 1163 dyne/sec/cm-5/mm2). By the treatment with PSL, massive pericardial effusion was gradually improved but DOE clinically unchanged. Second right heart catheterization was done on 8th of August. PAR was improved to 895 dyne/sec/cm-5/mm2 but PPA was elevated to 26 mmHg. It is very interesting that PPA was elevated although PAR was improved by PSL therapy. It is considered that the increase in venous return which was caused by improvement of massive pericardial effusion induced conversely the elevation of PPA. Additionally she was complicated with IgA deficiency. It may occur not only by the immunogenetical disorder such as HLA or IgG subclass alteration but also by anti IgA antibody or lymphocytes dysfunction complicated with SLE. PMID- 1925799 TI - [A case of pustulotic arthro-osteitis with secondary amyloidosis]. AB - A 63-year-old man with a history of Pustulosis Palmaris et Plantaris since 1960 was suffered from lumbago and anterior chest pain in 1973. Chest X-ray film showed inter-sterno-costo-clavicular ossification. Spondylodiscitis, Syndesmophyte of lumbal spine, Sacro-iliitis were seen by abdominal X-ray film. He was admitted to near hospital with generalized edema and urinary protein (10 20 g/day) in April 1986. Laboratory studies showed hypoproteinemia, positive C reactive protein, high serum amyloid A protein(240 ng/100 microliters) and negative HL-A B27. He was diagnosed Pustulotic arthro-osteitis and Secondary Amyloidosis by renal biopsy and rectal biopsy in 1987. He was treated with high dose oral prednisolone(60 mg/day)and dimethyl sulfoxide. After treatment, Edema and Nephrose improved. Increasement of renal function was not observed. PMID- 1925800 TI - [Fibromyalgia (fibrositis) syndrome--a case report]. AB - A 25-year-old woman was admitted in our hospital with back pain and both hip joint pain. Pain was abruptly occurred from the beginning of March 1990. Physical examination revealed wide spread pain (occipital area, both shoulder, lumber area, bilateral gluteal area, inguinal area, both Achilles-plantar area) and more than 12 tender points (occiput, trapezius, second rib, supraspinatus, gluteal, greater trochanter, hip joints, pubic bone). Laboratory examination showed no abnormal findings except ANF (1:160). Any examination including X-ray, bone scintigraphy, CT and MRI did not disclose spondylitis, sacroiliitis and enthesopathy. She was diagnosed as primary fibromyalgia/fibrositis syndrome. Treatment with maprotine hydrochloride (30 mg/day) and phenobarbital (120 mg/day) brought approximately 1/3 reduction of pain and tenderness. Psychoanalysis revealed that she had psychological conflicts against her parents and her colleagues at the work. EEG showed a borderline record with irregular basic pattern and 14 & 6 Hz positive burst at the sleep stage. Although the newly proposed criteria for the classification of fibromyalgia was proposed by ACR, fibromyalgia/fibrositis syndrome has been seldom discussed in the Japanese literature. As this syndrome is frequently associated with various rheumatic diseases, hypothyroidism and malignant diseases, we should pay much more attention to understand this syndrome. PMID- 1925801 TI - [A review on the role of synovial mesenchymal cells in the pathogenesis of rheumatoid arthritis]. PMID- 1925802 TI - [Sonography of joint disorders]. PMID- 1925803 TI - [A long-term evaluation of CN-100 in patients with rheumatoid arthritis]. PMID- 1925804 TI - Surgical management of mycotic aneurysms. AB - Mycotic aneurysms not associated with trauma or atherosclerosis are uncommon. Their clinical presentation is insidious and lacks definite diagnostic criteria. This retrospective study of 14 patients treated over a period of 9 years confirms this, and shows that half are associated with a predisposing infected focus and that the main presenting clinical feature is that of a painful mass (64%) which is often mistaken for some other diagnosis. The main extracranial, extrathoracic site of predilection was the iliofemoral segment (65%). The main diagnostic investigation was angiography, which was also used to uncover silent aneurysms elsewhere in the arterial tree. Urgent surgical treatment is mandatory since complications may occur at any time and these may include life-threatening bleeding. Two of our patients experienced life-threatening gastro-intestinal bleeding while in hospital. The mainstay of treatment was surgical resection and reconstruction using an autologous vein or artery if possible. The more serious complication of graft failure was encountered mainly in patients who underwent prosthetic graft repair. It is in this group that 2 of the 3 early postoperative deaths occurred, from graft thrombosis and mesenteric infarction. Overall, surgical repair was attended with good outcome (77%). PMID- 1925805 TI - Blunt splenic trauma in children. AB - Splenic trauma in 96 patients over an 11-year period is reviewed. Almost 80% of injuries resulted from motor vehicle accidents in which the patients was a pedestrian, and over 80% of patients sustained multiple injuries. Splenic injury was confirmed by isotope scanning at laparotomy. Non-operative management was feasible in 87.5% of the children, with no mortality or morbidity. In patients requiring surgery, splenic salvage was possible in 75%. PMID- 1925806 TI - Risk factors for complications after thyroid surgery. AB - Data on 60 patients who underwent thyroid surgery were retrospectively reviewed. The clinicopathological data were compared with the occurrence of the complications of recurrent laryngeal nerve palsy, hypocalcaemia and laryngeal oedema. Age, pressure symptoms and types of pathology were not associated with complications. Large glands and radiological evidence of a compressed trachea were statistically significant risk factors for postoperative complications. PMID- 1925807 TI - Intestinal presentation of phaeochromocytoma. A case report. AB - An unusual case of a patient with a phaeochromocytoma presenting with colitis is reported. A review of published reports showed a high mortality rate in patients with phaeochromocytoma complicated by intestinal disease. The importance of pre operative preparation with alpha-adrenergic blockers and removal of the tumour for the disappearance of intestinal symptoms is emphasised. PMID- 1925808 TI - [Gallstone disease in the elderly]. AB - The clinical manifestations, management and outcome of gallstone disease in 100 elderly patients are described. A total of 65 patients presented with a complication, acute cholecystitis (43), gallstone pancreatitis (8) and obstructive jaundice (6) being the commonest manifestations. The clinical picture was often misleadingly mild. Associated disease occurred in 70 patients but precluded surgery in only 3. Emergency surgery was indicated in 18 patients. Surgery was performed on 96 patients (cholecystostomy 2, cholecystectomy 94); 35 explorations of the common bile duct were done, with stones present in 33. Four patients died, 1 following an endoscopic retrograde cholangiopancreatography (ERCP) and 3 postoperatively (2 patients with gallstone pancreatitis); no death occurred following an elective operation. Alternative modalities of treatment of gallstone are expected to play a minor role in the management of gallstone disease in the elderly. PMID- 1925809 TI - Primary malignant melanoma of the oesophagus. Report of a case with flow cytometric DNA analysis. AB - Primary malignant melanoma is a very rare tumour of the oesophagus, and although this is the first case reported in a black patient in South Africa, the clinical, radiographic and histopathological features were characteristic of this malignancy. Primary oesophageal melanoma is a highly lethal tumour--fewer than 2% of patients are surviving 5 years after diagnosis. Flow cytometric DNA analysis of the resected specimen in this case revealed two populations of malignant cells, one of which had grossly abnormal DNA. Existence of two clones of malignant melanoma cells supports the observations that this tumour is biologically aggressive, radioresistant and almost always incurable. PMID- 1925810 TI - Results of surgery in idiopathic faecal incontinence. AB - The surgical treatment of idiopathic faecal incontinence remains a difficult problem, particularly in cases where advanced neuropathy is present. The physiological basis for the post-anal repair has now been questioned and the long term functional results seem to be rather unsatisfactory. Pelvic floor repair is a more comprehensive approach with encouraging initial results, which have now been shown in a prospective randomised trial to be superior to those of conventional post-anal repair. Gracilis transposition in idiopathic faecal incontinence has shown very disappointing results and probably has no role in the treatment of this condition. In very advanced cases intestinal stoma may occasionally provide important hygienic and psychological benefits. PMID- 1925811 TI - D.J. du Plessis Lecture. Liver preservation for transplantation. The more things change, the more they remain the same. PMID- 1925812 TI - Perindopril (Coversyl)--a new ACE inhibitor. Perindopril--a review of its pharmacokinetics and clinical pharmacology. PMID- 1925813 TI - Perindopril and reference antihypertensives. PMID- 1925814 TI - Reversal of structural changes in hypertensive arteries--a major prospect for the future. AB - Arteriosclerosis is the hallmark of hypertension and of its complications, namely stroke, coronary artery disease and ischaemic renal failure. The earliest morphological change in the arteriosclerotic process is vascular smooth muscle hypertrophy and hyperplasia. Angiotensin II is an important growth factor in vascular smooth muscle cells. The chronic administration of ACE inhibitors will reverse many of the changes of vascular hypertrophy in experimental animal models, and will improve vascular compliance in hypertensive patients. Some differences have been reported between different ACE inhibitors with respect to blood pressure-lowering effect and regression of medial hypertrophy in spontaneously hypertensive rats. PMID- 1925815 TI - Effects of perindopril on structural and functional changes in hypertensive arteries. PMID- 1925816 TI - Are more ACE inhibitors necessary? PMID- 1925817 TI - Control of occupational exposure to lead. PMID- 1925818 TI - Halothane hepatitis revisited. PMID- 1925819 TI - South Africa revisited--lessons to be learned from mistakes in American health care policy. PMID- 1925820 TI - Captopril, nifedipine and their combination for therapy of hypertensive urgencies. AB - Twenty patients with acute severe hypertension were randomised to therapy with either nifedipine capsules (10 mg) or captopril tablets (25 mg) given sublingually and the blood pressure recorded for 240 minutes. Oral monotherapy with either agent followed for 3 weeks, then the agents were combined for a further 2 weeks and in the final 6 weeks of the trial a beta-blocker and diuretic were added, if needed. Thirteen patients completed the trial. The major results were: (i) nifedipine decreased blood pressure more rapidly than captopril 60 minutes after first ingestion but at 240 minutes equal degrees of fall in blood pressure had been obtained; (ii) neither agent given as sustained monotherapy was able to reduce blood pressure adequately, although nifedipine was better than captopril; and (iii) combination therapy with both agents was conspicuously successful in achieving reduction in blood pressure. It is suggested that combination nifedipine-captopril therapy be subject to a formal trial for early therapy in acute severe hypertension. PMID- 1925821 TI - The causes of perinatal deaths in the greater Cape Town area. A 12-month survey. AB - A detailed analysis of 854 perinatal deaths according to both fetal and obstetric cause is presented. The ratio of stillbirths to neonatal deaths was 2.3:1. Almost 25% occurred in unbooked mothers. The major problems identified were preterm labour, unexplained stillbirth, abruptio placentae, infection, and protein-uric hypertension. PMID- 1925822 TI - Repeat laparotomy in ovarian carcinoma after primary surgery. AB - Thirty-two patients with malignant ovarian disease were referred after primary surgery to the Gynaecological Oncology Unit of Groote Schuur Hospital, Cape Town. All 32 patients underwent a re-laparotomy with a view to accurate staging and possible cytoreductive surgery. On referral, 24 patients (75%) had stage I or II disease and the remaining 8 patients (25%) had stage III and IV disease. Twenty seven patients (81%) had ovarian malignant disease of epithelial origin while the remaining 5 patients (19%) had ovarian disease of nonepithelial origin. Five (20.8%) of a total of 24 patients with stage I or II disease had their disease stage raised after repeat laparotomy. The overall success rate of cytoreductive surgery, i.e. less than 2 cm residual disease, was 58%. PMID- 1925823 TI - Carotid artery disease in young adults. AB - The angiographic and clinical findings in 17 young adults (14-39 years) with stenosis and/or occlusion of at least one of the common or internal carotid arteries were reviewed to determine the spectrum of carotid artery disease in this age group. Five aetiological groups were identified: atherosclerosis (3 patients), arteritis (4), non-inflammatory arteriopathies (6), compression by neoplasm (1), and occlusions of undetermined cause (3). Over a mean follow-up time of 19.7 months, 2 patients died (12.5%) and further cerebrovascular events occurred in 4 others (25%). We conclude that carotid angiography plays a meaningful role in providing a definitive diagnosis in young adults with carotid artery disease and thus may assist with therapy and prognosis. PMID- 1925824 TI - The incidence of retinopathy of prematurity at Groote Schuur Hospital, Cape Town. AB - Retinopathy of prematurity (ROP) continues to occur in nurseries world-wide because more immature babies are surviving the neonatal period. In order to establish the incidence and severity of this disease at Groote Schuur Hospital, 141 very-low-birth-weight infants were examined; 27 (19.2%) were found to have ROP, and among these 2 (1.56%) had a particularly severe form of the disease. None of the infants required treatment. The incidence and severity of ROP is compared with similar studies, and the monitoring of oxygen therapy and screening of infants is discussed. PMID- 1925825 TI - Non-attendance of psychiatric outpatients. AB - The failure of discharged psychiatric inpatients to attend for continuing outpatient treatment is an important factor in readmission. A study of 136 such patients indicates that frank resistance to treatment and inadequate information given to patients and their families are important contributing factors. A recommendation for improving the situation is made. PMID- 1925826 TI - Psychiatric morbidity in outpatients with systemic lupus erythematosus. AB - A study group of 25 patients with systemic lupus erythematosus (SLE) and a control group of 25 with rheumatoid arthritis (RA) attending a routine outpatient clinic at Groote Schuur Hospital were psychiatrically evaluated. The patients were assessed using two structured interview tools: the Present State Examination and the Mini-Mental State Examination. The results showed a relatively high prevalence of neurotic depression in both groups (40% in SLE and 32% in RA). Ratings of tension, worry and social unease were high in both groups. No psychoses or organic disorders were found. Steroid usage did not appear to have contributed to psychiatric symptoms. It is suggested that the psychiatric morbidity in this group of SLE patients was due to psychosocial rather than organic factors. PMID- 1925827 TI - Purification of human erythrocyte porphobilinogen deaminase. AB - Human erythrocyte porphobilinogen deaminase was isolated using ammonium sulphate fractionation and heat treatment, Sephadex G-25 and G-100 chromatography, di ethylamino-ethyl anion-exchange chromatography, chromatofocusing over a pH gradient of 7-4 and, finally, hydrophobic interaction chromatography on a phenyl Sepharose column. The enzyme appeared pure as judged by sodium-dodecylsulphate polyacrylamide gel electrophoresis with silver staining, and yielded a 7 115-fold purification. PMID- 1925828 TI - Sunbeds and solaria--a warning. PMID- 1925829 TI - Osteoid osteoma involving the vertebral body. PMID- 1925830 TI - Diagnosis of HIV-1 infection in the newborn. PMID- 1925831 TI - Continuous spinal anaesthesia with microcatheters. PMID- 1925832 TI - Evaluation of AIDS prevention programmes--the key to success. PMID- 1925833 TI - Natural foods--are current restrictions excessive? PMID- 1925834 TI - Poorly performed lung function tests--the answer is not blowing in the wind. PMID- 1925835 TI - Arterial phase left atrial opacification in acute massive pulmonary embolism. AB - Classic angiographic features in acute massive pulmonary embolism include main or lobar arterial branch cut-off, and/or arterial filling defects with matching impaired venous drainage. Six haemodynamically compromised patients with acute massive pulmonary embolism (mean pulmonary artery pressure 55 +/- 12 mmHg), confirmed by pulmonary arteriography, are described. Early opacification of the left atrium during the arterial phase of the pulmonary angiogram was seen in all patients. Follow-up pulmonary arteriography after successful thrombolytic therapy was performed 4 days later in 2 cases. A marked haemodynamic improvement was accompanied by resolution of the previous abnormal angiographic signs, including early opacification of the left atrium. The latter might be a response to intensive reactive vasodilatation of the remaining perfused lung fields resulting in a more rapid pulmonary transit time and the opening of arteriovenous channels with further systemic desaturation. This angiographic sign is a marker of severe, but reversible, vasoconstriction in acute massive pulmonary embolism. PMID- 1925836 TI - The significance of the carotid bifurcation angle in carotid body tumours. AB - This is a retrospective report on 22 patients with carotid body tumours (intercarotid paragangliomas or carotid chemodectomas) treated by excision using either the dissection technique or en bloc resection. The type of operation to be carried out can be predicted pre-operatively by measuring the carotid bifurcation angle or degree of splaying of the carotid arteries. An angle of less than 90 degrees implies that the tumour can be dissected off the internal carotid artery. An angle of more than 90 degrees implies that it will probably require en bloc resection, including the carotid bifurcation, followed by carotid reconstruction. PMID- 1925837 TI - [The effect of enalapril and prazosin on mild to moderate hypertension in black South Africans]. AB - A double-blind, placebo-controlled clinical trial with a parallel design was conducted on 35 black patients with mild to moderate hypertension. After a 4-week run-in on placebo, baseline values were recorded and only patients with diastolic pressures of 95 - 115 mmHg were admitted to the trial, which lasted 10 weeks. These patients were randomised in three groups, receiving daily initially either 5 mg enalapril, 2 mg prazosin or placebo. Blood pressures and heart rates were measured once every week and in poor responders dosages were increased on a 2 weekly basis. Enalapril was increased to 10, 20 and 40 mg during the last 4 weeks, and prazosin was respectively increased to 4, 10 and 20 mg. The only statistically significant difference between baseline and post-treatment values (week 10) was a reduction in heart rate in the prazosin group, but no differences in either systolic or diastolic pressure could be detected in this group or between any of the three measurements in the other two groups. When the mean values of 3 groups were compared on a weekly basis it transpired that there were no statistically significant differences between any of the baseline values but that the mean heart rate at week 2 and the mean diastolic pressure at week 9 in the prazosin group and the mean systolic pressures in the enalapril group at weeks 6, 8 and 10 were significantly lower than the corresponding placebo values. Cumulative sum techniques were used to measure the course of the effects of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1925838 TI - Neurocysticercosis in 578 black epileptic patients. AB - In a study of 578 epileptic patients at the Ga-Rankuwa Hospital, 281 had abnormal computed tomography (CT) of the brain (48.6%), and in 162 (average age 32 years) there was evidence of cysticercosis (57.6%). In 68 of the infected patients (41.9%) active cysts were seen on CT. Neurocysticercosis, either active or inactive, was thus implicated in 28% of this group of epileptic patients, which emphasises the importance of this disease in the causation of epilepsy in the black population of South Africa. PMID- 1925839 TI - The tuberculosis epidemic--why we are slipping up. AB - Bedletters of 100 diagnosed cases of tuberculosis from Kalafong Hospital, Pretoria, were reviewed retrospectively. All patients were followed up to evaluate treatment and notification. An overall treatment failure rate of 13% was recorded, mainly due to non-compliance by patients referred to clinics. There was an undernotification rate of at least 48%. PMID- 1925840 TI - A comparison of cross-sectional and longitudinal survey methods in measuring patient compliance with tuberculosis treatment. AB - A group of 179 tuberculosis patients, notified within a specific time period in an area served by a community-based TB clinic in Cape Town, was defined. Cross sectional and longitudinal measurements of compliance were taken to test the validity of the two research methods in compliance surveillance. The cross sectional method was found to mask significantly the true extent of non compliance with tuberculosis treatment (19.5% v. a true 40.3%). The sampling and measurement biases inherent in the cross-sectional design were illustrated. The first bias was introduced because the cross-sectional survey captured only treatment survivors. By the date of the cross-sectional survey 45 patients were no longer on the clinic treatment list, between 4 and 13 (2.2 - 7.3% of the original group) having been lost as a result of poor compliance. The second and most extensive bias was introduced because the cross-sectional survey measured the compliance of all patients on a particular day irrespective of the time since notification. Thus for the cross-sectional group the compliant proportion was 80.5% at the time of the cross-sectional survey but fell to 65.4% by the end of treatment (as measured in the longitudinal survey). The absolute significance of the association between compliance and various demographic and treatment variables did not change with survey method. However, in two instances the association approached significance in only one of the two surveys. The study implies that serious clinical repercussions are possible if management decisions are based on the results of inappropriately designed studies. The place of the longitudinal and cross-sectional research methods in compliance surveillance is discussed. PMID- 1925841 TI - Medical education--maladies, myths and misconceptions. PMID- 1925842 TI - Sexual behaviour and knowledge of AIDS among urban black mothers. Implications for AIDS intervention programmes. AB - Questionnaires were administered to 122 urban black mothers of teenagers in order to: (i) understand aspects of their sexual behaviour and knowledge of the acquired immunodeficiency syndrome (AIDS); and (ii) assess their communication with their teenage children with regard to AIDS and sexual behaviour. The subjects comprised a 12.5% random sample of all houses in Lamontville, a black township south of Durban. The level of AIDS knowledge among mothers was high, while their sexual behaviour, characterised by a high pregnancy rate and a high proportion who have had children by more than one consort, placed them at high risk of acquiring human immunodeficiency virus (HIV) infection. No mother had experienced sexual intercourse during which her partner used a condom. Communication with their teenage children was poor; none of the mothers had spoken with them about AIDS and 89.3% had not discussed contraceptive methods with their teenage children. We found that urban black mothers were at high risk of acquiring HIV and, despite their knowledge of the modes of transmission and prevention of HIV infection, they had not begun using condoms as a risk-reducing measure, nor had they communicated the risk of unprotected sex to their teenage children. We recommend that AIDS intervention strategies should not concentrate only on passing on knowledge but also on providing women with the communication skills to negotiate the use of condoms with their partners and to convey the risk of HIV infection to their teenage children. PMID- 1925843 TI - Evaluation of an AIDS awareness campaign using city buses in Johannesburg. AB - The Johannesburg City Health Department embarked on an AIDS awareness campaign using messages placed on the outside of 30 city buses. The selection of the message and the campaign are outlined briefly. An evaluation to assess the overall effectiveness and the cost-effectiveness of using buses as a "vehicle' for exposing the local community to AIDS awareness messages is described. Two cross-sectional studies using telephone interviews were done 2 1/2 and 6 months after the campaign began; 30.2% and 31.5%, respectively, of respondents had seen the message. Accurate recall of the message was generally poor. The overall cost of the campaign was R7 627. Various other aspects of the study are discussed. The study revealed that signs on buses are a cost-effective means of conveying simple and brief health-related messages. PMID- 1925844 TI - National strategy for viral hepatitis: recommendations and guidelines for management in South Africa. PMID- 1925845 TI - Easier needle bladder-neck suspension procedure. PMID- 1925846 TI - Fish oil supplementation and cardiovascular disease. PMID- 1925847 TI - Trichothecene mycotoxins--a new entity? PMID- 1925848 TI - A model for investigating the systemic effects of adrenaline in dental local anaesthetic solutions in patients under surgical stress. AB - A model has been developed which permits the investigation of the systemic effects of adrenaline injected during dental local anesthesia. The model employs patients undergoing the removal of third molars under general anaesthesia. This design allows the study of the effects of exogenous adrenaline administration in clinical doses in patients experiencing surgical stress. In the present investigation the influence of the intra-oral injection of 50 micrograms adrenaline contained in lignocaine local anaesthetic solution on haemodynamic and biochemical responses was established by comparing the effects of inferior alveolar block injections of 4 ml 2% lignocaine and 4 ml 2% lignocaine with 1:80,000 adrenaline in 20 patients having third molars removed with a standardised general anaesthetic regime. No significant changes in haemodynamic responses between treatments were apparent, however significant changes occurred between treatments in blood glucose and plasma potassium levels. PMID- 1925849 TI - Applications of laser surgery in gynecology. Hype or high tech? AB - Despite the proliferation of the use of lasers in gynecology, physicians in both private practice and the academic setting remain skeptical about the role of these instruments. The laser has not made it possible to perform surgical procedures that have previously been impossible to carry out in the operating theater. Further, as yet, higher pregnancy rates have not been achieved with any reconstructive procedure using the laser rather than conventional or electrocautery surgery. On the other hand, surgeons such as Daniell reported on the impact of laser in decreasing the need for laparotomy in their practices. For instance, prior to the introduction of the laser, Daniell performed laparotomy on 80% of his patients with endometriosis, pelvic adhesive disease, or tubal disease, whereas currently he performs 80% of these procedures through the laparoscope. However, one could argue that this change simply represents the trend of performing more gynecologic procedures through endoscopes whether a laser is involved or not. Convincing evidence exists that pelviscopy results in savings in terms of morbidity and the cost of surgery. Whether endoscopic surgery can be performed more safely using the laser than with a traditional technique has not been addressed in a formal study. Whether laser surgery produces better pregnancy rates is unresolved. Ninety per cent of all clinical trials involving the laser have been uncontrolled. Those studies that have been controlled, reported by Tulandi, for example, have shown results at least equivalent to those achieved with diathermy, and it is of interest that the pregnancies tended to occur sooner in the laser-treated groups. The laser is at least as effective as electrocautery in the treatment of adhesions and distal tubal disease. Therefore, it is the author's recommendation that all types of lasers be used in conjunction with electrocautery and conventional sharp dissection in the treatment of various forms of pelvic pathology. It is important that surgeons become familiar with all types of lasers, as future devices may be vastly different and prove to be clearly superior in treating the various pelvic pathologies. PMID- 1925850 TI - Ovarian cancer. Advances in management. AB - Substantial progress has been made in understanding the biologic behavior of ovarian cancer and in assessing disease states and response to therapy with transvaginal sonography, CT scan, and tumor markers such as CA-125. There is no longer controversy regarding the importance and feasibility of adequate surgical staging, the need for cytoreduction, and the utility of cisplatin- or carboplatin based combination chemotherapy in the management of patients with ovarian cancer. Increasing chemotherapy dose through escalated systemic doses or intraperitoneal administration, revising multidrug resistance, the use of biologic response modifiers, and the development of new methods of chemosensitivity testing may help improve the current 5-year survival rate of less than 30% for patients with stage III ovarian cancer. Significant improvement in screening tests and diagnostic capabilities will be necessary for a dramatic increase in survival. PMID- 1925851 TI - Selection of incisions for gynecologic procedures. AB - Progress is being made in the employment of abdominal incisions. The use of mass closure has greatly decreased the incidence of disruption. The avoidance of subcutaneous sutures has likewise decreased the rate of wound infections, and modern aggressive management has lessened the time that patients must contend with incisional abscesses when they do occur. There will always be considerable discussion and debate on the choice of an abdominal incision. However, the primary consideration remains always to choose and construct a surgical incision large enough to operate through comfortably and effectively. PMID- 1925852 TI - Surgical aspects of cervical cancer. AB - Surgery maintains an important role in the diagnosis and treatment of premalignant as well as early invasive and recurrent cervical cancer. Although the indications for and benefits of surgical staging remain to be determined, specific procedures frequently are necessary to manage treatment-related complications. The authors review the indications, morbidity, and outcome of these procedures. PMID- 1925853 TI - Surgery for stress urinary incontinence. AB - Stress urinary incontinence is a common problem, with various degrees of disability. Its etiology may be defective external or internal urethral sphincter mechanisms. Evaluation of the patient with symptoms of stress incontinence requires objective testing for diagnostic accuracy. Patient management may be individualized to conservative measures or to one of the various surgical approaches, which produce success rates between 80% and 95%. Retropubic suspension or long needle procedures should be considered for patients with stress incontinence and evidence of bladder neck detachment. Sling procedures, artificial sphincters, and periurethral injections should be considered for patients with minimal bladder neck mobility or low urethral pressures and for those with a high risk of failing other procedures. PMID- 1925854 TI - Surgery for vulvar cancer. AB - In recent years, data have been accumulated regarding risk factors for metastatic potential and have improved the understanding of the pathways and frequency of lymphatic dissemination. Proper application of this information allows individualization of treatment to obtain optimal cure rates with minimum morbidity in patients with vulvar malignancy. PMID- 1925855 TI - Surgery for pelvic floor disorders. AB - By careful observation of the physical findings in the patient complaining of one of the disorders of genital prolapse, it should be possible to discern the origin of the symptoms and therefore to devise an appropriate treatment that would remedy by reconstruction all of the signs of anatomic weakness. The goals of reconstructive surgery are three: to relieve the symptoms, to restore the anatomy to normal, and to restore the function to normal. When any element of weakness in the pelvic floor is found to be sufficient to produce symptoms that warrant repair, it is the responsibility of the surgeon to identify all the sites of weakness, so that all may be repaired at the same time, sparing the patient the expense, pain, and inconvenience of future readmission for further surgery. These weaknesses all relate to deficiencies of the six major organ systems that are involved in the support of the female pelvis, which may be damaged singly or in any combination. There are various types of cystocele, each of which must be carefully excised if an appropriate surgical treatment is to be given. This may involve correction of cystocele, enterocele, rectocele, prolapse of the uterus, and posthysterectomy prolapse of the vaginal vault. With enterocele, it is possible to correlate the four common types of enterocele with their location, which in turn correlates directly with their treatment. The prevention of complications is emphasized along with the treatment of certain mechanical complications easily recognized at the time of surgery. PMID- 1925856 TI - Urinary tract injuries in pelvic surgery. AB - In this article, we have reviewed the scope of surgically induced damage to the lower urinary tract. Preventative and reparative techniques have been presented. As pelvic surgeons become more confident in their efforts to safeguard the urinary tract, the chance of an unrecognized injury causing morbidity will diminish. PMID- 1925857 TI - Surgical management of radiation enteropathy. AB - Acute radiation enteropathy is usually self-limited and rarely requires surgical intervention. Chronic radiation enteropathy may occur months, years, or decades after treatment. Patients may present with crampy abdominal pain, diarrhea, or cachexia or may present acutely with bowel obstruction or fistula. The bowel and its mesentery are shortened, and mucosal ulceration and submucosal fibrosis are present. The vasculature of the bowel is markedly compromised by progressive endarteritis. Ideally, nutritional support should be given and surgery performed electively. Regardless of presentation, both large and small bowel must be evaluated for concurrent problems. At surgery, resection and restoration of continuity of the gastrointestinal tract is optimal management. Recurrent obstruction and fistulae are real risks, and optimal management is resection of bowel damaged by radiation and anastomosis using bowel spared from irradiation. However, if the patient is unstable or necessary dissection and mobilization of the bowel judged too morbid, bypass of the affected loop is acceptable. Occasionally, only diversion of the bowel by enterostomy is possible. PMID- 1925858 TI - Endometrial cancer. Changing concepts in therapy. AB - All patients with adenocarcinoma of the endometrium should have a total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal cytology study, and pelvic and para-aortic node biopsies when feasible. Patients with stage Ia disease do not need further therapy and have an excellent prognosis. Patients with stage Ib or Ic disease are at some risk for recurrence and should be considered for pelvic radiation, although their survival may be unaltered by this treatment. Patients found to have stage IIIc disease on the basis of metastases to the pelvic nodes should receive whole-pelvic radiation. Patients with multiple metastatic sites or with clear-cell or serous papillary adenocarcinomas should be considered for whole-abdominal radiation or other systemic treatment. Surgical staging with pelvic and para-aortic node biopsies is important, as it allows the clinician to make individualized treatment decisions based on accurate data and known prognostic factors. PMID- 1925859 TI - Renal cell carcinoma with inferior vena cava tumor thrombi. AB - Renal cell carcinoma is a unique neoplasm because of its common propensity to propagate into the renal vein and inferior vena cava (IVC) as tumor thrombus. Historically, the surgical difficulties encountered in removal of these cancers limited the ability of a single institution to obtain experience with large numbers of instances. Between January 1956 and July 1987, 68 patients with renal cell carcinoma extending into the IVC or right atrium underwent radical nephrectomy with vena cava thrombus extraction at the Cleveland Clinic. Twenty five patients had partial resection of the IVC with reconstruction. Fifteen patients had partial resection and reconstruction of the IVC; however, because of narrowing of the infrarenal IVC, persisting bland thrombus in the proximal IVC or iliac veins or concern regarding postoperative pulmonary emboli, the infrarenal IVC was either ligated or clipped. Seven patients underwent cavectomy with division of the IVC. A right atriotomy was performed upon 14 patients and cardiopulmonary bypass was used in 20 patients, with 17 also having deep hypothermic circulatory arrest. The tumor thrombus was removed intact in 64 per cent of the patients and in multiple small fragments ("piecemeal") in 36 per cent of the patients. The mortality rate was 7 per cent. Survival was examined relative to extent of vena caval thrombus. Patients with extension into the atrium had a significantly worse prognosis than those with other levels of vena caval involvement. Other factors, such as lymph node status, perinephric fat involvement, resection of IVC and intact or "piecemeal" extraction, did not influence the survival rate. Patients with pre-existing metastases preoperatively had an extremely poor survival rate. The techniques now available for surgical resection of all levels of tumor thrombus of the IVC make resection feasible in most patients. In our opinion, the addition of deep hypothermic circulatory arrest has been a significant advance. PMID- 1925860 TI - Continuous intercostal nerve block for postoperative analgesia after surgical treatment of the upper part of the abdomen. AB - Continuous intercostal nerve block can be used effectively for pain relief after abdominal operations. We have developed a greatly simplified technique instituted by the surgeon at operation using bupivacaine hydrochloride (Marcain, ASTRA). Our method proved to be effective in providing postoperative analgesia in 93.4 per cent of the patients undergoing cholecystectomy through a transverse abdominal incision. No additional analgesia was required in the first four days postoperatively while the system was in use. In addition, no postoperative pulmonary complications or adverse reactions to bupivacaine hydrochloride or the procedure were encountered. This method proved to be a success in postoperative pain relief and we highly recommend that it be used routinely. PMID- 1925861 TI - Knee replacement in morbidly obese women. AB - Sixty-six total knee replacements in 50 morbidly obese women with osteoarthritis were performed. The results in these patients were compared with 64 knee replacements in 50 nonobese women and with 50 obese women who did not have knee replacement operations. All obese patients were advised by a physician to lose weight and were counseled by a dietician. Five obese patients with six replaced knees and four nonobese patients were lost prior to follow-up study. Follow-up examinations were performed after 24 to 60 months, with mean of 33 months, in the remaining patients. No significant sustained weight loss occurred in the obese patients who had knee replacement operations or in obese patients who did not have surgical treatment. Eighty-six per cent of nonobese patients had excellent or good results from knee replacement surgical treatment. Fifty-seven per cent of morbidity obese patients had excellent or good results. There were two infections and two revision operations in morbidly obese patients and no infections and one revision in nonobese patients. Total knee replacement is safe and reasonably effective in the morbidly obese. However, the results are not comparable with those achieved in nonobese patients, and knee replacement should not be expected to facilitate weight loss. PMID- 1925862 TI - Postoperative radiation therapy does not increase survival after curative resection for squamous cell carcinoma of the middle and lower esophagus as shown by a multicenter controlled trial. French University Association for Surgical Research. AB - In 1978, postoperative radiation therapy was suggested to be an additive treatment of carcinoma of the esophagus. In 1987, we began a multicenter trial of patients with epidermoid carcinoma of the middle third or the lower third of the esophagus. Isolated surgical treatment (119 patients) was compared with surgical treatment followed by radiation therapy (102 patients). Randomization was performed according to the results of pathologic examination of all resected lymph nodes. Patients were divided into three groups: N0, no lymph node invasion; N+1, invasion of paraesophageal lymph nodes, and N+2, invasion of distal lymph nodes (recurrent, tracheal and celiac). All patients included in this trial had a curative esophageal resection. In the group receiving radiation therapy (102 patients), a total dose of 45 to 55 Grays was delivered in the mediastinal, right and left supraclavicular areas and also to the celiac area when celiac lymph node invasion was present. Two hundred and twenty-one patients were randomized and observed from three to nine years; life table method (log rank method) was used to compare survival and local recurrence. In all patients studied, the survival rate was significantly higher (p less than 0.01) in patients without lymph node invasion (group N0) than in patients with lymph node invasion (groups N+1 and N+2). Postoperative radiation therapy did not improve survival in any group. This lack of improvement in survival was present regardless of lymph node status. However, there were significantly fewer recurrences in patients receiving radiation therapy as compared with those not receiving radiation therapy. PMID- 1925863 TI - Transabdominal esophagomyotomy and partial fundoplication for treatment of achalasia. AB - The most common surgical treatment for achalasia is a modified anterior extramucosal esophagomyotomy. Unfortunately, a poor outcome may result secondary to recurrent dysphagia or gastroesophageal reflux. The reported incidence of reflux is 4 to 50 per cent. Our treatment for achalasia is an esophagomyotomy carried onto the cardia combined with a partial gastric fundoplication. Of 22 patients who presented with achalasia and moderate to severe symptoms of dysphagia and odynophagia, 19 had this procedure performed. Of these 19 patients, only two required a second procedure (postoperative dilatation) for recurrent symptoms. All three patients who had a full fundoplication required further surgical correction. Although fundoplication has been condemned in the past as treatment of achalasia to avoid the postoperative outcome of reflux, we have been successful with a partial fundoplication added to the standard esophagomyotomy. Given the fine line that needs to be tread to prevent recurrent signs and symptoms of achalasia or reflux when performing esophagomyotomy, our procedure offers a viable alternative to transthoracic esophagomyotomy alone. PMID- 1925864 TI - Complications of biopsy of the cervical lymph node. AB - The incidence of injury to the accessory nerve after biopsy of the cervical lymph nodes is difficult to ascertain. The deficits in trapezius muscle function can result in marked disability to the patient. We have presented the results of surgical exploration and repair in eight patients with injury to the accessory nerve during biopsy of the cervical lymph node. External and internal fascicular neurolysis and fascicle suturing when indicated were performed. Four patients received significant improvement in accessory nerve function and four had no improvement. Our findings agree with those reported in the literature that early recognition of accessory nerve dysfunction after biopsy of the posterior cervical lymph node with appropriate surgical therapy can yield excellent results in trapezius muscle function. PMID- 1925865 TI - A uniform approach for esophagectomy with or without thoracotomy. AB - In patients with carcinoma of the esophagus, it is advisable to perform a total esophagectomy. We prefer a cervico-abdominal procedure and use the stomach to reconstruct the alimentary tract. Sometimes the operation needs to be extended with a right-sided thoracotomy. We have used this method of positioning and draping successfully in more than 70 patients in the last two years. This method enables us to perform a three stage operation if necessary without repositioning the patient and renewed preparation of the operative field. PMID- 1925867 TI - Use of a table-based retractor for improved axillary exposure during modified radical mastectomy. PMID- 1925866 TI - Roux-en-Y jejunoduodenostomy for endoscopic access to hepaticojejunostomy. PMID- 1925868 TI - Digital augmentation during repair for a paravaginal defect. PMID- 1925869 TI - A modified Seldinger technique for peritoneal lavage in trauma patients who are obese. AB - We have devised a technique of peritoneal lavage that combines the semi-open and the Seldinger techniques for use in trauma patients who are morbidly obese that is fast, safe and obviates the extensive incision that is required to adequately visualize the peritoneum when using the open method. We have successfully used this technique in six patients whose weight exceeded the weight limit of 135 kilograms of our CT scanner. PMID- 1925870 TI - Ureteral catheter for laser fiber delivery in endometrial ablation. AB - A method of quartz laser fiber delivery in endometrial photocoagulation ablation is described. This may help protect and facilitate manipulation of the fragile quartz fiber used during this procedure. PMID- 1925871 TI - Intermittent claudication. AB - The natural history of intermittent claudication is generally benign. Clear indications for revascularization in patients with intermittent claudication are rest pain and necrotic tissue. Disabling claudication in patients who are at low operative risk is another acceptable indication for surgical treatment. Young patients with intermittent claudication from aortoiliac occlusion constitute a subset of patients in whom a more aggressive approach is justified. Nevertheless, in most patients, the management of intermittent claudication should be conservative. PMID- 1925872 TI - Diagnosis and management of vesicoenteric fistulas. AB - Vesicoenteric fistulas represent challenging clinical problems and may be characterized by difficulty in diagnosis as well as controversy in management. We present our experience with 56 patients with vesicoenteric fistulas. The results of our series were compared with a report of 1,100 in the literature during the past 20 years. Fecaluria (48 per cent), abdominal pain (43 per cent) and pneumaturia (41 per cent) were the most common presenting symptoms among the patients we studied. Fistulas were most frequently attributable to diverticulitis (52 per cent), Crohn's disease (18 per cent), carcinoma of the colon (11 per cent) or other pelvic malignant conditions (9 per cent). The most accurate diagnostic modalities in our series were cystoscopy (88 per cent), cystography (56 per cent) and barium enema (32 per cent). The combined findings of these studies led to the diagnosis of a fistula in all patients. Intravenous urography, intestinal endoscopy and computed tomography were less useful, providing a diagnosis in only 5, 6 and 11 per cent, respectively. Surgical treatment was single staged in 57 per cent and multistaged in 35 per cent, while 8 per cent of the patients underwent intestinal diversion only. Comparison of the single versus multistaged approaches revealed that the total complication rate, frequency of additional procedures, rate of infectious complications and length of hospitalization were no higher for the single stage group. Based on these findings, we advocate single stage repair, except in those patients who have unusual complications. PMID- 1925873 TI - Control of bleeding is essential for a successful treatment of hemorrhagic shock with 7.5 per cent sodium chloride solution. AB - Small volume hypertonic saline (HTS) solution resuscitation has been shown to restore hemodynamic derangements and to protect against mortality in "controlled" hemorrhagic shock (CHS), but it exacerbates the shock state in "uncontrolled" hemorrhagic shock (UCHS). To study the mechanisms associated with the divergent outcome of HTS treatment in CHS versus UCHS, HTS was administered to anesthetized rats (n = 7) subjected to 15 per cent resection of the tail followed by controlled or uncontrolled bleeding. HTS treatment of UCHS increased bleeding (13.3 +/- 1.6 milliliters, p less than 0.05), dropped mean arterial pressure (MAP) (-84.5 +/- 8.9 millimeters of mercury, p less than 0.001), central venous pressure (zero millimeters of mercury, p less than 0.001) and cardiac index (CI) (41 per cent of basal value, p less than 0.001) and increased acidosis (pH 7.23 +/- 0.12, p less than 0.05) and mortality (mean survival time 75 +/- 15 minutes versus 122 +/- 23 minutes of untreated rats, p less than 0.05). In contrast, when administered after application of a ligature proximal to the resection site (at 15 minutes), HTS completely reversed the changes in MAP, CI and total peripheral resistance index (TPRI), and improved mean survival time (172 +/- 7 minutes, p less than 0.05). These data support the assumption that HTS should be used in the treatment of hemorrhagic shock only after bleeding was controlled. PMID- 1925874 TI - The effect of size of giant pancreatic pseudocysts on the outcome of internal drainage procedures. AB - Pancreatic pseudocysts (PP) that fail to resolve spontaneously are optimally treated by internal drainage to a viscus. Pseudocysts adherent to the stomach are usually drained by way of cystgastrostomy. Recent experience with giant pseudocysts (greater than 15 centimeters), however, challenges this approach. Fifty-two patients with pancreatic pseudocysts of various sizes were treated from 1982 to 1986 at the Massachusetts General Hospital. Twenty-eight PP were suitable for internal drainage. The postoperative complication rate was directly proportional to the size of the pseudocyst. Four patients had giant PP, three of which occurred after an attack of acute pancreatitis. All four were treated by cystgastrostomy. Three of four patients with giant pseudocysts had life threatening postoperative complications as a result of incomplete emptying of the cyst, and two patients died. No evidence of anastomotic leakage could be demonstrated by upper gastrointestinal series or computed tomographic scans. Transgastric drainage tubes in these three instances were not protective. We conclude that cystgastrostomy may not be appropriate for the treatment of giant pancreatic pseudocysts because it fails to provide dependent drainage of a large cyst cavity. If internal drainage is performed, the cyst should be anastomosed to a defunctionalized loop of jejunum in a dependent position. In some instances, external drainage of giant pancreatic pseudocysts may be safer than cystgastrostomy. PMID- 1925875 TI - Factors influencing the rupture of abdominal aortic aneurysms. AB - The gross findings of 49,144 autopsies performed at two major hospitals in Rome were reviewed. There were 297 patients who were found to have atherosclerotic abdominal aortic aneurysm (AAA). The aneurysm was intact in 220 (74 per cent) and ruptured in 77 (26 per cent). The occurrence of aneurysm rupture was correlated to 17 variables by univariate and multivariate statistical analysis. Covariates found to be independently predictive of the rupture of AAA were the size of the aneurysm (p less than 0.001), arterial hypertension (p less than 0.001) and the presence of bronchiectasis (p less than 0.025.). Over-all, bronchiectasis was more common among patients with AAA than in the age-adjusted and sex-adjusted control population. The simultaneous presence of bronchiectasis and AAA suggests the presence of some inherited or acquired tendency to have ectasia of the connective tissue, aneurysm formation and rupture development. PMID- 1925876 TI - The role of the Argon Beam Coagulator in splenic salvage. AB - To assess the effect of the Argon Beam Coagulator (ABC) (Bircher Medical Systems) on splenic salvage, 160 adults sustaining blunt traumatic splenic injuries over a 39 month period were evaluated. The survey period includes the first 15 months during which the ABC was used and the immediate 24 months before the use of the ABC (pre-ABC). In addition to the difference in splenic salvage in the two groups with deep laceration without hilar injury (15 versus 53 per cent), the Injury Severity Score (ISS) (44.2 versus 34.5) and Glasgow Coma Score (GCS) (11.4 versus 13.8) were significant. Multivariate logistic regression analysis revealed a significant relationship between splenic salvage and ISS (r2 = 0.27, p = 0.001) with ABC (r2 = 0.07, p = 0.02). However, if GCS is added to ISS and ABC as a factor, it does not provide additional information (p = 0.37). We conclude that the use of the ABC in the management of blunt nonhilar splenic injuries significantly improves the prospect for successful splenorrhaphy. PMID- 1925877 TI - Surgical management of vesicovaginal fistulas according to Chassar Moir's method. AB - Aside from the more common perioperative and postoperative dysfunctions of micturition, urogenital fistulas represent the most frequent complication encountered after surgical gynecologic interventions. Vesicovaginal fistulas are the most common communication between efferent urinary passages and the genital tract. From 1967 to 1987, 42 women had a vesicovaginal fistula develop after abdominal or vaginal operations and underwent another operation. At admission, all 42 patients had surgical closure of the vesicovaginal fistula according to the vaginal method of Moir. In 41 women, continence was re-established by adequate closure. PMID- 1925878 TI - Bronchial suction by minitracheotomy as an effective measure against sputum retention. AB - Bronchial suction by means of a minitracheostomy is a new method for treatment of sputum retention and related pulmonary diseases. Through a small coniotomy, a specially designed cannula is inserted into the trachea, allowing frequent bronchial suction. The effectiveness of this method was prospectively analyzed in 74 consecutive patients and the results were compared with those reported in the literature. The operative procedure for insertion of the Minitracheotomy cannula caused nonlethal bleeding in three patients who were receiving anticoagulant medications. Thirty-eight of 43 patients treated on the intensive care ward were detubated and dismissed at an earlier stage than usual because of a minitracheostomy. The method failed in two comatose patients and in one patient with a laryngeal tumor. The method was effective in 18 patients who had serious pulmonary disease postoperatively. Thirteen patients at high risk for pulmonary infections, in whom the cannula had been prophylactically applied after extensive operations, did not have postoperative pulmonary complications. Over-all, the median period for bronchial suction was 4.0 days; decannulation followed on average 4.7 days later. No complications were caused by the presence of the cannula and the device was well tolerated by the patients. PMID- 1925879 TI - Intraoperative fine needle aspiration cytologic examination of pancreatic lesions. AB - Despite the possibilities in modern imaging technology and percutaneous biopsy, a surgeon may still find an undiagnosed mass in the pancreas at laparotomy. In this situation, intraoperative fine needle aspiration cytologic (IFNAC) examination has been reported to be helpful. We reviewed our experiences with IFNAC in 98 patients. Fifty patients had a malignant pancreatic tumor as verified on histologic examination. The results of IFNAC correctly suggested a malignant tumor in 35 patients, for an initial sensitivity of 70 per cent. Re-examination of the slides resulted in 81 per cent sensitivity, which was not a significant improvement. The sensitivity rate (an average of 83 per cent in the literature) does not, however, express enough the unreliability of the method in individual patients. We conclude that, although IFNAC correctly differentiates between carcinoma and benign pancreatic diseases in most instances, the justification for pancreas resection cannot always be based on cytologic findings, but rather on clinical and laparotomy findings. PMID- 1925880 TI - The use of the supraceliac aorta for hepatic arterial revascularization in transplantation of the liver. AB - Thrombosis of the hepatic artery during the early post hepatic transplant period results in massive hepatocyte necrosis, bile duct damage and subsequent graft loss. The incidence of this complication is increased when hepatic arterial reconstruction is possible only by the placement of an interposition infrarenal iliac artery graft. We describe 45 hepatic transplants with difficult arterial reconstruction in which the supraceliac aorta was used for arterial reconstruction. Indications for using the supraceliac aorta as the primary site for arterial reconstruction were inadequate inflow through a narrow recipient common hepatic artery in 51 per cent, previously thrombosed common hepatic artery in 27 per cent, mechanical obstruction of the celiac axis in 13 per cent or intimal dissection in 9 per cent. Direct anastomosis of the donor hepatic artery to the supraceliac aorta was achieved in 22 patients, reducing the need for a graft by 49 per cent. Short segments of iliac artery graft (17 patients) or aortic conduit (six patients) to the supraceliac aortas were required because of insufficient length of the donor artery. The incidence of arterial thrombosis and graft loss were zero per cent in adults and 12.5 per cent in children, both significantly less when compared with the 23.0 to 70.0 per cent thrombosis rate when graft is placed in an infrarenal position. We conclude that routine use of the supraceliac aorta for difficult hepatic arterial reconstruction decreases the need for arterial grafts, the incidence of hepatic arterial thrombosis and loss of hepatic grafts. PMID- 1925881 TI - Limitations of percutaneous catheter drainage of abdominal abscesses. AB - During the past eight years, 119 patients with abdominal abscesses underwent percutaneous catheter drainage (PCD), including 76 who had successful treatment by the initial PCD, 19 who had recurrent abscesses after removal of drainage catheters and 24 who were outright failures and either died of sepsis or required surgical drainage. This study was designed to identify outcome variables that might be used prospectively to assess the therapeutic efficacy of PCD. Outcome variables included abscess size, daily drainage volume and location, presence of a gastrointestinal fistula, age, bacteriologic factors and response of the pulse rate, body temperature and leukocyte count of the patient to PCD. Ninety of 119 patients (76 per cent) ultimately had successful drainage of abscesses by PCD alone. The over-all mortality rate was 16 per cent (19 of 119), with a 75 per cent mortality rate in the failure group. Neither abscess size, bacteriologic findings nor pulse rate correlated with outcome. PCD failure was significantly greater in patients greater than or equal to 60 years (p less than or equal to 0.01) and in patients with pancreatic abscesses versus other locations (p less than or equal to 0.04). Drainage volume was significantly greater in PCD failures than among PCD successes at greater than or equal to 3 days after PCD (p less than or equal to 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1925882 TI - The mistaken diagnosis of carcinoma of the ovary. AB - The primary site of carcinoma was investigated in 339 women diagnosed as having carcinoma of the ovary. After a review of medical records and microscopic slides, 43 women were discovered not to have a primary carcinoma of the ovary. Of these 43 women, 15 had benign ovarian tumors, 13 had primary carcinoma of the peritoneum and 15 had primary carcinoma of the intestines. Review of the medical records of 15 women found to have benign ovarian tumors disclosed the original pathologic interpretation of cancer was not supported by clinical or operative observations and no second opinion pathologic review was noted in the records. Until our review, 13 women who were diagnosed as having carcinoma of the ovary had primary peritoneal tumors. Nine of these women either had normal ovaries removed previously or had normal results of biopsies of the ovary done intraoperatively. Of those women entering the study with a diagnosis of carcinoma of the ovary, but in whom our review noted carcinoma of the intestines, 14 of 15 had intestinal complaints before operation. More than one-half of the patients did not have the intestine studied preoperatively, most had diffuse disease at operation and almost one-half of the women had normal sized ovaries at operation. By not performing gastrointestinal roentgenographic studies and suspecting the possibility of metastasis and by misleading the pathologist by presenting the specimen as an ovarian tumor, patients were erroneously diagnosed as having primary carcinoma of the ovary. PMID- 1925883 TI - Successful combined hepatic and pancreatic allograft retrieval in donors with a replaced right hepatic artery. AB - The parallel development of reconstructive techniques used to retrieve and transplant organs with vascular anomalies, and of techniques used in the multiple organ retrieval process, have facilitated the recovery of the maximal number of transplantable organs from a limited supply of donors. Recent contributions to this effort are descriptions of combined retrieval of both liver and whole organ pancreaticoduodenal allografts from the same multiple organ donor. Suggested contraindications for the retrieval of the latter allograft have included the presence of a replaced right hepatic artery originating from the superior mesenteric artery. We describe herein the techniques used in retrieving both the liver and the whole pancreas from donors with this vascular anomaly. PMID- 1925884 TI - Prognostic factors in adenocarcinoma in the upper one-third of the stomach. AB - From 1965 to 1985, 356 of 1,468 patients (24.3 per cent) with carcinoma of the stomach who underwent gastric resection had disease arising from the upper one third of the stomach. Tumors in the upper one-third of the stomach were larger, and gross appearance of types 3 and 4 was frequent. Serosal invasion was prominent, and the rates of metastases of the lymph nodes and liver were higher in carcinoma in the upper one-third of the stomach compared with carcinoma in other regions of the stomach. Palliative resection was done for 43.8 per cent of the patients. Survival rate for patients with carcinoma in the upper one-third of the stomach was lower than for patients with lesions in other regions of the stomach (p less than 0.01). Multivariate analysis indicated that operative curability, hepatic metastasis, serosal invasion, lymph node metastasis, peritoneal dissemination and tumor size are significant prognostic factors for carcinoma in the upper one-third of the stomach. These events, except for peritoneal dissemination, differed between carcinoma in the upper one-third of the stomach and in other regions of the stomach, and the survival rate for patients with carcinoma of the upper one-third of the stomach was less favorable. Early detection is crucial for improving the survival time of patients with carcinoma in the upper one-third of the stomach. Aggressive postoperative chemotherapy should be considered when noncurative resection is done. PMID- 1925885 TI - Teaching mechanical ventilation. AB - Participants have stated that having actually experienced the modes of the ventilator and the components of weaning parameters, they are better able to understand and manage ventilated patients, as opposed to trying to memorize them as in the past. They also have a much greater appreciation for the discomfort experienced by the ventilated patient. (Most students cannot tolerate a PEEP of 10 centimeters of H2O for more than a few minutes). Many remarked that they are much more tolerant with their agitated, intubated patients because they can now understand their agitation. The session has proved to be an effective teaching tool. It is cost effective, does not take long and is enthusiastically received by the participants who believe they have gained a better understanding of how to properly care for their anxious, intubated patients. PMID- 1925886 TI - The simultaneous injection and evacuation technique for viable echinococcal cysts. PMID- 1925888 TI - Extension of the right renal vein in cadaveric renal transplants with use of the vena cava and the TA-30 V3 surgical stapler. AB - The aforementioned technique offers an expeditious and safe means of extending the cadaveric right renal vein for 3 to 5 centimeters, while greatly minimizing the ischemic time of the kidney during preparatory dissection. The cuff of the cadaveric right renal artery can also be preserved, and the danger of kinking of the arterial graft is minimized. Our experience has shown that separation of the left renal vein 3 to 4 millimeters away from the vena cava allows a left renal vein of adequate length for transplantation of the left kidney. Between June 1985 and August 1989, we have used this technique successfully in more than 120 cadaveric right renal transplants and have seen no vascular complications attributable to the stapled conduit of the vena cava. PMID- 1925887 TI - Use of a nasogastric tube and a Nelaton catheter for esophageal reconstruction. AB - An effective technique for leading a nasogastric decompression tube using an endoscopic foreign-body or biopsy forceps guided Nelaton catheter during esophageal reconstruction is described herein. This technique is both time-saving and avoids unnecessary mucosal damage to the esophagus. PMID- 1925889 TI - Expansion of the venous outflow tract in arteriovenous grafts of the forearm using antebrachial venoplasty. AB - The use of venoplasty to widen the antecubital venous outflow during the placement of arterio-venous grafts in the forearm for angioaccess is described. This has allowed an increased use of grafts for the forearm for angioaccess in instances in which antecubital veins were otherwise believed to be inadequate in size. Expansion of the venous outflow tract may also increase the long term patency of these grafts. PMID- 1925890 TI - A simple technique to tighten a loose suture during vascular anastomosis. PMID- 1925891 TI - The doctors and the Constitution. PMID- 1925892 TI - Volvulus of the sigmoid colon. AB - Volvulus of the sigmoid colon is an important condition, with multifactorial causes, that occurs worldwide, but with a marked variation in geographic incidence. Accurate diagnosis is essential for optimal management. Most patients can be managed by nonoperative decompression followed by elective resection of the sigmoid colon. When emergency laparotomy is necessary, resection is generally the best procedure. However, individualization of treatment is appropriate in medically compromised patients or in special circumstances. Current knowledge suggests that primary prevention is not possible, so better management is essential if the number of deaths associated with volvulus of the sigmoid colon are to be reduced. Sound clinical judgment still has an important role in the diagnosis and management of this disorder. PMID- 1925893 TI - An objective method to measure and manage occult pneumothorax. AB - Of 457 patients with multisystem injuries undergoing abdominal computed tomographic (CT) scan, 26 patients were found to have 31 pneumothoraces. None of these were apparent on prior roentgenograms of the chest. Each pneumothorax was quantified by measuring its maximal width in millimeters and the number of 10 millimeter CT sections on which it appeared. Serial roentgenograms of the chest and patient charts were reviewed. The major factor determining the clinical course and management of these pneumothoraces was size. Seventeen per cent of pneumothoraces measuring less than 5 X 80 millimeters (group 1) and 85 per cent of those measuring greater than or equal to 5 X 80 millimeters (group 2) had tube thoracostomy performed. The percentage of pneumothoraces in each group with positive pressure ventilation was 55 and 77 per cent, respectively. Our results suggest that such occult pneumothoraces may be managed with close observation if they measure less than 5 X 80 millimeters, whether or not the patient is to receive positive pressure ventilation. Larger pneumothoraces and those associated with more than two rib fractures may require early treatment. PMID- 1925894 TI - Computed tomography in the evaluation of blunt abdominal trauma. AB - The role of computed tomography (CT) in the evaluation of victims of blunt abdominal trauma remains controversial. This study was done to assess the reliability of CT in the evaluation of blunt abdominal trauma at our institution, to determine if the incidence of nontherapeutic laparotomy has decreased with the use of CT scan and to review the time necessary to complete the scans. Of the 325 patients studied, 37 per cent were found to have abdominal injury on CT scan. Thirty patients required laparotomy; ten of these were nontherapeutic. Excluding transport time, abdominal CT scan required 55 +/- 20 minutes to complete. Abdominal CT was accurate when read by attending physicians (97.5 per cent). Major shortcomings included the commitment of time and personnel, transfer of the patient from a critical care area and reliance on experienced interpretation. PMID- 1925895 TI - Iatrogenic injuries to the ureter during gynecologic and obstetric operations. AB - Iatrogenic injuries to the ureter are hazardous complications of pelvic and vaginal operations, causing severe morbidity and even mortality. Eighteen such instances that occurred during the last 30 years are analyzed. Most of the injuries were associated with attempts to achieve hemostasis without proper identification of the ureter. The incidence of ureteral injuries declined during the years concomitantly with the improvement of surgical techniques. The proper identification and, when necessary, isolation of the ureter during operations in which there is a risk is crucial in reducing the incidence of ureteral injuries. Those diagnosed at the time of injury and treated with end to end anastomosis had the best results. Delayed diagnosis and treatment were associated with poor end results. The English literature is reviewed. PMID- 1925898 TI - Operative procedures not involving the heart after percutaneous transluminal coronary angioplasty. AB - The benefit of coronary artery bypass grafting (CABG) in patients with coronary artery disease (CAD) who require extensive surgical procedures not involving the heart has been established. During the past decade, percutaneous transluminal coronary angioplasty (PTCA) has been developed as an alternative therapy to CABG for patients with CAD. In an attempt to determine the safety of other surgical procedures after PTCA, we retrospectively reviewed 148 patients who underwent 193 surgical procedures from four to 1,867 days after PTCA for CAD. Seventy-two patients had surgical treatment within 90 days of PTCA. Thirty-five patients had CABG prior to PTCA, and 113 had PTCA as the initial treatment for CAD. Four patients died postoperatively, only one death was cardiac in origin. One patient had a myocardial infarction postoperatively (the one cardiac death). Fifteen patients had other cardiac complications (nine patients with arrhythmias and six with myocardial ischemia). Patients operated upon within 90 days of PTCA had no increased cardiac morbidity, although the one myocardial infarction occurred in this group. No difference in cardiac morbidity occurred in patients with multivessel CAD treated by PTCA compared with single vessel disease. However, patients more than 60 years of age had more cardiac problems (16 of 110) than those less than 60 years of age (zero of 38) (p = 0.01). Treatment of CAD by PTCA protects the myocardium from fatal cardiac events and myocardial infarction during subsequent noncardiac operative procedures even early (less than 90 days) in the post-PTCA period. Older patients seem to be at higher risk, however, for nonfatal cardiac complications. PMID- 1925896 TI - Estrogen receptor determination and long term survival of patients with carcinoma of the breast. AB - To investigate whether or not hormone receptor determination gives independent prognostic information for long term survival of patients with carcinoma of the breast, we studied 1,392 patients with early carcinoma of the breast. Patients were part of two prospective, multi-institutional trials, the first begun in 1974 and the second in 1980. Estrogen receptor assays were performed on all primary specimens taken of the carcinoma of the breast. Initial treatment for all patients was a modified radical mastectomy. Nine hundred and seventeen patients had negative axillary nodes and were observed without additional therapy. Four hundred and seventy-five had positive nodes and were randomized to receive combination chemoendocrine adjuvant therapy. One thousand and sixty-three (76.4 per cent) of the patients were found to have estrogen receptor positive (ER+) tumors (greater than or equal to 3 femtomoles per milligram cytosol of protein). The ten year over-all survival rate of 65.9 per cent was significantly better than that of 329 (23.6 per cent) patients with estrogen receptor negative (ER-) tumors (less than 3 femtomoles per milligram cytosol protein), who had a ten year over-all survival rate of 56.0 per cent (p = 0.0001). Higher estrogen receptor values were associated with Caucasian (p = 0.0001) and postmenopausal patients (p = 0.0001). In a proportional hazards regression model, patients with ER+ tumors had a significantly longer over-all survival period (p = 0.0001), but only a marginally improved disease-free survival time (p = 0.07) when compared with patients who had ER- tumors. These results indicate that ER determination does have prognostic value for long term over-all survival of patients with carcinoma of the breast. The greater importance of ER analysis to over-all compared with disease-free survival may be related to more easily managed recurrent disease among the ER+ group. PMID- 1925897 TI - Evaluation of renal transplant dysfunction using color Doppler sonography. AB - Color Doppler sonography (CDS) detects changes in renal blood flow that may be useful in evaluating renal transplant dysfunction (RTD). To assess the performance of CDS as a clinical test, we reviewed results from 223 CDS measurements in 130 renal transplant recipients during a 26 month period. Spectral wave forms were characterized by pulsatility index (PI) (maximum frequency shift minus minimum frequency shift divided by mean frequency shift). In 27 individuals with stable renal function, mean PI was 1.80 +/- 0.23 (S.D.). Abnormal PI were subsequently defined as greater than two S.D. more than the mean (PI greater than or equal to 2.3). CDS performed during the early post-transplant period (n = 91) could not differentiate acute tubular necrosis (ATN), obstruction and rejection. Abnormal studies were seen in 35 of 46 instances of ATN and in three of obstruction. In 132 studies done after the postoperative period, CDS became abnormal during rejection episodes in only 45 of 71 instances (sensitivity rate of 63 per cent). When abnormal, CDS was highly suggestive of rejection, however (45 of 49, 92 per cent specificity). Cyclosporine toxicity was not associated with abnormal pulsatility (zero of seven). In 68 instances, CDS and conventional 99mTc DTPA renogram flow studies were performed together within 24 hours. CDS was more sensitive in detecting rejection but the difference did not reach statistical significance (25 of 36 versus 17 of 36). The major advantage of CDS over conventional radionuclide imaging relates to its shorter examination time, lower cost and portable capabilities. CDS will probably become the roentgenologic imaging modality of choice in renal transplantation. PMID- 1925899 TI - Results, complications and surgical indications of the Florida pouch. AB - One hundred and seven patients underwent continent urinary diversion using an extended, detubularized right colonic segment as the urinary reservoir and the distal part of the ileum as a continent catheterized efferent system. This reservoir allows the accommodation of a large volume of urine; urodynamics in 28 patients demonstrated a maximum reservoir capacity varying between 550 and 1,200 milliliters (an average of 747 milliliters). The reservoir maximal volume and pressure remains unchanged in six patients studied urodynamically three to four years postoperatively. Maximal reservoir pressures ranged between 10 and 58 centimeters of H2O (an average of 35 centimeters). Of 201 ureterocolonic reimplantations, four ureters were initially reimplanted using a modified Le Duc procedure, 26 ureters were subsequently managed using the Goodwin transcolonic approach and 165 reimplantations were done with a direct (nontunneled) mucosa to mucosal anastomosis. The over-all success rates with each of the three techniques (absence of reflux and obstruction) have been 75.0, 84.7 and 87.4 per cent, respectively. However, the incidence of obstruction was 13.3 per cent for the tunneled and 4.2 per cent for the non-tunneled reimplantations. Six megaureters underwent imbrication and direct reimplantation, and three of these became obstructed. One patient died of pulmonary embolism. Medical and surgical complications markedly predominated in the group who underwent simultaneous cystectomies, and in this group, the over-all complication rate was comparable with that for previously reported series with ileal conduits. The double row plication of the distal part of the ileum and ileocecal valve allows easy catheterization every four to six hours and 105 patients (97.2 per cent) remained continent between catheterizations. The stoma is covered using a small gauze, cap or sterile adhesive strip. This protects clothing from mucus production by the stoma and an occasional episode of urinary dribbling. Seven patients required reoperation for correction of incontinence or other complications. Our satisfactory experience with these patients makes this technique an excellent approach to achieving continent urinary diversion. PMID- 1925900 TI - A novel combined operative and radiotherapeutic treatment approach for recurrent gynecologic malignant lesions infiltrating the pelvic wall. AB - Patients who have recurrent gynecologic malignant conditions infiltrating the pelvic wall still have a poor prognosis, although based on the biologic factor of the tumor, 50 per cent might be salvaged if local control is achieved. For patients with unilateral disease, we have designed a combined operative and radiotherapeutic treatment (CORT) that involves subtotal resection of the tumor, intraoperative placement of guiding tubes for postoperative high dose rate brachytherapy of the residual tumor and tumor bed at the pelvic wall and pelvic wall plasty with autologous tissue flaps. We use either flaps of the greater omentum and inferiorly based rectus abdominis muscle flaps from the abdominal route or (de-epithelialized) gluteal thigh flaps from the vaginal and perineal route to cover the tumor bed and overlying tubes. Thus, a protective distance between the radiation source and radiointolerant pelvic organs is created and the risk of local infection and hypoxia is reduced. With this combination of surgical and radiation treatment, the therapeutic ratio between tumor control and tissue damage in the pelvic area is thought to be improved. Higher local doses can be applied compared with conventional methods in instances in which surgical treatment has been performed and reirradiation with tumoricidal doses may be possible after primary or adjuvant radiation therapy. The encouraging first experience with the CORT concept in nine patients with a short follow-up period is reported. PMID- 1925901 TI - Proposed new criteria for early carcinoma of the esophagus. AB - The criteria of early carcinoma of the stomach, defined in 1981, has gained worldwide acceptance. A few proposals of a criteria for early carcinoma of the esophagus have been made; however, these criteria have not been internationally accepted, as the rate of recurrence is high in patients with early carcinoma of the esophagus, as determined by these criteria. In patients with submucosal carcinoma of the esophagus, metastasis to lymph nodes was present in 32.5 per cent at the time of the operation, and the five year survival rate was only 54.5 per cent. On the other hand, while the incidence of epithelial or mucosal carcinoma, or both, is only 2.2 per cent (46 of 2,130) in patients with carcinoma of the esophagus, the incidence has been remarkably increased and the five year cumulative survival rate for patients with epithelial carcinoma or mucosal carcinoma, or both, is now 88.4 per cent. Thus, we consider that the criteria for early carcinoma of the esophagus to be mucosal carcinoma as well as epithelial carcinoma regardless of the presence or absence of lymph node metastasis, and that a submucosal carcinoma should be excluded from the classification of early carcinoma of the esophagus. PMID- 1925902 TI - The significance of mammographic findings after breast-conserving therapy for carcinoma of the breast. AB - Mammographic changes after lumpectomy, axillary dissection and irradiation are common and unpredictable. To study the significance of these changes at the first follow-up mammogram, we retrospectively reviewed reports of 172 women treated in this manner between 1979 and 1988. The mean follow-up time was 50 months. Eight patients had recurrences in the same breast, while 13 patients had carcinoma develop in the opposite breast. The mean time of follow-up mammograms was 11 months (range of one to 48 months). Twenty-six patients had a normal mammogram, while 146 patients had some changes within the irradiated breast. Thirty-one patients had suspicious findings--a mass, speculation or new microcalcifications. None of these 31 patients had carcinoma confirmed by biopsy or follow-up examination. Of eight patients with recurrence in the same breast, six had a biopsy because of findings on physical examination, while two had changes from previous mammograms. The mean time to recurrence was 50 months (range of 24 to 81 months). We conclude that mammographic changes in the irradiated breast are common after lumpectomy and irradiation for carcinoma of the breast. A baseline mammogram should be done six months after irradiation is completed. Changes that occur at this time should be considered secondary to surgical treatment and irradiation and are not an indication for immediate biopsy. These findings should be reconfirmed by a mammogram performed one year after irradiation to prove that these changes are stable. Physical examination and yearly mammography of both breasts are imperative in the follow-up evaluation of patients treated in this manner. PMID- 1925903 TI - Improved methods in long term venous access using the P.A.S. Port. AB - An over-all lower cost implantable chronic venous access is readily accomplished using the Cath-finder and implantable P.A.S. Port. This system has few complications and is less expensive, time saving and easy to maintain. The Cath finder system allows the surgeon to access accurately the central venous circulation without the use of a fluoroscope. The implantable P.A.S. Port has wide acceptance with many types of patients, including those with tumors, cystic fibrosis and AIDS. PMID- 1925904 TI - Suprarenal mesocaval shunt. AB - A new technique for performing a mesocaval shunt above the level of the renal veins is described. It should be considered an option for those patients with perirenal vena caval occlusion or obstruction who require surgical decompression of the portal venous system. PMID- 1925905 TI - Suturing angiodysplastic lesions of the small intestine. AB - Suturing angiodysplastic lesions of the small intestine during perioperative enteroscopy is a quick and simple method with a minimal chance of complications. The technique described herein is a reliable tool that can be used repeatedly in the same procedure. PMID- 1925906 TI - Stapled anastomosis for trans-sphincteric resection of the rectum. AB - We have found that in all patients who have undergone this procedure, normal defecation and complete continence are maintained. The surgical wound heals well and functional results have been uniformly good, even in instances in which only 1 centimeter of the rectum remains. This procedure may be useful for patients who are carefully diagnosed by preoperative transrectal ultrasonography in which the lower edge of the rectal tumor is within 8 centimeters of the anal verge, the tumors do not extend into the muscularis propria and there is no lymph node metastasis. Use of the CEEA stapling device can shorten the time of operation and is particularly beneficial for elderly patients and those who are at poor risk. PMID- 1925907 TI - Prognostic applications of DNA analysis in solid malignant lesions in humans. AB - Analysis of the DNA of tumors using flow cytometry is a technologic method that can be used to investigate the biologic nature of tumors. While not conclusive, results suggest that this biologic information may be useful in identifying patients with malignant disease who have a worse prognosis. The differentiation of patients with aneuploid tumors into those with hypoploid tumors and those whose tumors are hyperploid may be a further refinement of the technique. Also, a combination of this biologic criteria may allow a more accurate selection of patients than either method alone. Further investigative work needs to be done to fully evaluate the clinical usefulness of flow cytometric DNA analysis and answer these and other questions. PMID- 1925908 TI - International Abstracts of Surgery. PMID- 1925909 TI - Nutrient foramina in the shafts of lower limb long bones: situation and number. AB - The location and number of the diaphysial dominant nutrient foramina in 305 specimens of the human lower limb long bones were examined. The diaphysial nutrient foramina on the femur were located at between 26.7-84.4% of the total length; while on the tibia between 11.0-67.2%; and on the fibula between 29.8 67.8% of the total length. The number of the diaphysial nutrient foramina and their distribution on the faces of each bone was also studied. PMID- 1925911 TI - The arterial circulation of the left suprarenal gland. AB - The findings in a study of the general circulation of the suprarenal glands in 25 cases, and particularly of the left glands in 50 cases, are presented. The vessels arose from three pedicles: superior, middle and inferior. The inferior pedicle was the most irregular, with a frequent contribution from the gonadal artery to the inferior part of the gland; this artery should not be regarded as merely an accessory vessel. On the left side an inconstant posterior pedicle, separate from the others, was found in 26% of cases. Two forms of gonadal artery supplying the gland (8%) are described, an upper origin type at the renal artery level and an aberrant type. PMID- 1925910 TI - Upper thoracic dorsal rami: anatomic study of their medial cutaneous branches. AB - The authors describe the distribution of the medial branches of the upper thoracic dorsal rami (T1 to T5 levels). At each level, after travelling through the erector spinae, they become superficial, and reach the apex of the spinous process of the corresponding vertebra. They then spread out laterally, innervating the skin. They can occasionally be compressed by paravertebral tendons, and this possibly contributes to certain forms of dorsal pain. Anastomosis of the dorsal cutaneous branch of the second thoracic nerve (T2) with the descending lateral branch of the accessory nerve has been observed. Its presence could explain the occasional clinical situations where there is no resultant paralysis from accidental surgical section of the latter nerve. PMID- 1925912 TI - Number and size of perigastric lymph nodes in human adults without gastric cancer. AB - For classification of perigastric lymph node metastases in gastric cancer, only topographical aspects are taken into consideration at present. As a numerical classification for lymph node metastases was proposed recently, the current problem is that of determining the number of dissectable perigastric lymph nodes and also assessing the quality of nodal dissection. The perigastric lymph nodes of 10 adults without gastric disease were therefore evaluated microscopically by a serial section technique. On average a total of 36.2 +/- 15.2 perigastric lymph nodes were found, e.g. 14.9 +/- 14.1 lymph nodes on the greater and 7.4 +/- 4.8 on the lesser curvature. These figures are similar to those in fetuses and newborn infants, but they exceed the numbers of perigastric lymph nodes reported in the literature for adults with or without gastric cancer. This difference could be attributable to our use of the serial section technique, because the so called "micro-lymph nodes" with a diameter of less than 1.5 mm are consequently included in this study. Our results support the assumption, that pathologic processes do not result in any real increase of regional lymph nodes, but in an activation and enlargement of fetal lymph node reserve. PMID- 1925913 TI - The surgical anatomy of the sinoatrial node. AB - The sinoatrial nodes (SAN) were observed, dissected, and measured on 95 adults and 30 child hearts under a dissection microscope. The majority of the SANs in adults are characterized by their pale color, firm consistency, and the location in relation to the penetration of the SAN artery, and they can be located in the superior part of the terminal sulcus. The SANs in children, however, are not easily discerned. The variation of the apex of the right auricular crest and the notch in the superior part of the terminal sulcus have been described, and the present authors suggested that the trigone of the SAN could be used as an important landmark to identify the SAN. The surface features on the SAN, its relationship to the surrounding myocardium and its surgical significance during operation are further discussed. PMID- 1925914 TI - MRI evaluation of the levator ani muscle: anatomic correlations and practical applications. AB - A comparative study of serial anatomic sections in the transverse, frontal and sagittal planes with corresponding MRI sections of the pelvis allowed the authors to define the most suitable sectional planes and MRI modes for a morphologic study of the levator ani muscle. This study shows the value of MRI examination in the assessment of anorectal malformations. PMID- 1925915 TI - Anatomic and experimental basis for the insertion of a screw at the first sacral vertebra. AB - The authors present the anatomic and experimental basis of an original technique for screwing at the first sacral level employed in lumbosacral fusion. The anatomic studies were based on specimens from the anatomy museum, frozen sections of the sacrum and CT examinations with three-dimensional reconstruction and assessment of the density of the different structures of S1 in Hounsfield units (HU). The findings were that the ala and lateral portions of S1 contain yellow marrow forming what amounts to a fatty sphere bounded by the cortical bone of the sacroiliac joint, the linea terminalis and the spongy bone of the pedicles and of the body of S1. The experimental study was made by avulsion of sacral screws (system of Cotrel Dubousset), each of 7mm diameter. No screw perforated the sacral cortex. Three directions were tested. The insertion of a screw through the pedicle and body of S1 is advised, with the point of insertion below and lateral to the articular process of S1 and an oblique course forward and inward at an angle of 10 degrees to the sagittal plane. This internal obliquity is limited by the posterior prominence of the iliac ala. PMID- 1925916 TI - The "critical zones" of entrapment of the nerves of the lower limb. AB - The author has studied, in a group of 40 dissections on cadavers of individuals of different ages, the main "critical zones" of entrapment of some terminal branches of the lumbo-sacral plexus, which include canals (fibrous, osteo fibrous, fibro-muscular), intervals (intermuscular, fibro-muscular, musculo ligamentous), rings (fibrous or fibro-muscular) and foramina. They provide the topographical anatomical basis for possible compressive phenomena of the nerves of the lower limb. PMID- 1925918 TI - Mediastinal lymphatic pathways of the azygos and aortic arches: injection based on segments of the adult lung. PMID- 1925917 TI - The anatomical basis and prevention of neurogenic voiding dysfunction following radical hysterectomy. AB - The disorder of neurogenic dysfunction is one of the most important complications of radical hysterectomy. In order to prevent this potential complication, the authors have studied the composition and layers of the pelvic paravisceral structures. The nerve branching and distribution of the pelvic plexus of 12 adult female cadavers were analyzed. From lateral to medial the pelvic paravisceral structure is made up of three layers. The lateral layer is the pelvic visceral fascia, the middle, a vascular layer, and the medial one, a nervous one which consists of the pelvic plexus and subsidiary plexuses. The pelvic plexus and subsidiary plexuses are laid closely to the lateral walls of pelvic organs. The ischial spine was taken as the central point and two perpendicular lines penetrating through the ischial spine were used as the longitudinal axis and transverse axis. According to these landmarks, the pelvic plexus could be divided into three parts: behind the longitudinal axis are the roots of the pelvic plexus, near the longitudinal axis is the uterovaginal plexus, and in front of the longitudinal axis are the branches distributed to bladder and urethra. The pelvic plexus and the uterosacral and cardinal ligaments are closely related. The pelvic and subsidiary plexuses can be damaged in radical hysterectomy and voiding dysfunction may then develop. Some anatomic bases are provided to explain and hopefully prevent this from happening. PMID- 1925919 TI - Anterior interosseous artery: anatomic bases of pedicled bone-grafts. PMID- 1925920 TI - The commissuro-mamillary plane in MRI of the brain (preliminary communication). AB - MRI sections of the brain in the coronal plane through the line joining the anterior commissure and the mamillary bodies display the constituent parts of the basal forebrain. The visualisation of the septal nuclei and the anterior columns of the fornix show the importance of this plane in the study of behaviour disorders and amnesic syndromes. PMID- 1925921 TI - Anatomic basis for conservative surgery of the spleen. AB - 100 pancreatico-splenic blocks obtained at autopsy were treated by the injection corrosion method. The splenic artery ended in the lienorenal ligament in 64% of cases, in the pancreatic segment in 32% and in the hilar segment in 4%. In 84% of cases, the artery divided into two lobar arteries, upper and lower. In 16% the artery trifurcated. The pedicle was 20 to 60 mm long (mean 35 mm). The branches of the splenic artery were in three successive stages: the primary or lobar arteries were each associated with a lobe; the secondary or segmental arteries each supplied one of the constituent segments of a lobe; the tertiary or subsegmental arteries supplied the various areas which made up a splenic segment. Nine cases of extraparenchymal anastomoses were found. There were 32 intraparenchymal anastomoses, being either interlobar or intersegmental. There were a few interlobar anastomoses. The findings support the notion of upper and lower intersegmental and interlobar planes. The latter is almost avascular, while the former has limited vascularity. These planes make conservative surgery of the spleen possible. PMID- 1925922 TI - An anatomical study of the lymphatic drainage of the gallbladder. AB - Based upon the detailed dissections of the lymphatic system of four adult cadavers, the lymphatic drainage of the gallbladder was divided into three pathways. 1) The cholecysto-retropancreatic pathway, which can be regarded as the main pathway, had two routes, one running spirally and posteriorly from the anterior surface of the common bile duct to the right, and the other running almost straight down from the posterior surface of the common bile duct. At the retroportal segment, these routes converged at a large lymph node, which appeared critical as the main terminal lymph node of this pathway. We designated this node the principal retroportal node. 2) The cholecysto-celiac pathway was the route by which some of the lymphatics from the gallbladder ran to the left through the hepatoduodenal ligament to reach the celiac nodes. 3) The cholecysto-mesenteric pathway was the route by which some of the lymphatics ran to the left in front of the portal vein and connected with the nodes at the superior mesenteric root. These three pathways converged with the abdomino-aortic lymph nodes near the left renal vein; in particular, the nodes in the interaortico-caval space were considered important. PMID- 1925923 TI - [Complex movement analysis: dynamic study of the effect of a tape bandage on pronation in high-jumping with three-dimensional movement analysis and electromyography]. AB - Overuse syndromes in the lower extremity are a frequent problem in athletics, especially in jumping events. Athletes notice a comfortable support by using ankle taping without restriction of their performance. Up to now no objective data is available about efficiency of taping against overpronation which is frequent in high jumping. In high jumping without boots little difference of pronation between taped and untaped take off leg was found. In contrast in jumping with spikes boots a marked pronation during take off was found, which was reduced by ankle taping with a reduction of maximum medial malleolar medialisation by 77%, reduction of pronation time by 33% and time of maximum pronation by 8.2% in the take off leg. Surface electromyography showed an increased activity of M. peroneus longus by 30.7% as a plantarflector and pronator muscle with ankle taping. Activity of other jump supporting muscles of the lower extremity was little influenced. PMID- 1925924 TI - [Accident causes and prevention of injuries in Enduro-motorbike sport]. AB - 365 participants of the 64. Enduro-World Championship in 1989 reported 232 injuries within a 10-years-period of motorbike driving. The knee was most frequent (21.5 pc., mainly ligament ruptures) injured, followed by fracture of the clavicle (18.5 pc.), hand (15.5 pc.) and damages of the shoulder. Fractures are very common (55.5 pc.) in motorbike sports. Injuries often were produced by collisions with other motorbikes or trees. Driving mistakes, jumps, slipping wheels and overturn were other causes for an accident. During the championship 13 accidents were registered. In a clinical examination defects or alterations of the joints and bones were observed at 91 drivers. Important is the incidence of two malign tumours of the testicles. Preventive measures against accidents are discussed. PMID- 1925925 TI - [GOTS (Society of Orthopedic Traumatologic Sports Medicine) five years old]. PMID- 1925926 TI - [Treadmill versus field trial. Movement analysis and pressure distribution in the athletic shoe]. AB - Our current knowledge on interactions between runner and runningshoe is mainly based on treadmill measurements. In order to reveal stress load and adaptation on playing surfaces it was necessary to develop a combined measuring device out of 3 D video motion analysis and portable pressure measurement system. By means of a motor driven cart moving parallel to the subject with comparable position of cameras to the treadmill test it was possible to set up an identical trial for track and field. 12 subjects (male, age 24-32, size 9) were tested at a speed of 2.8 m/s. The varying conditions were treadmill and grass and two different constructed running shoes. 200 cycles and over 1000 steps were analyzed. The quantitative analysis of 37 parameters describing the contact phase was performed using the wilcoxon test for paired samples.-A qualitative comparison of running styles was introduced by using angle-angle-diagrams (knee and ankle by 3-D data) similar to those first described for 2-D by P.R. Cavanagh in 1973. It showed a huge interindividual variability under same conditions. Comparing the angle-angle diagrams for the four different running conditions it was possible to classify them into three characteristic groups: non-adaptors, surface-adaptors and shoe adaptors. Comparing track and field to treadmill measurements significant differences were found for the knee at impact: On treadmill the initial knee angle was 4.6 degrees more extended at a 13% higher angle velocity and a 30% higher angle deceleration (sig. p less than 0.05). A 7.3% higher impulse was found on grass at a 5.9% higher step length. No difference in maximum pressure was found. These results show that adaptation is performed mainly by the knee. Changing the motion pattern the knee seems to be capable of homogenizing the different stress loads to the foot. Comparing the running shoes significant differences were found in the motion of the ankle: a controversial behaviour was found to be on treadmill and grass. The pressure data revealed significant differences for the treadmill test to be in the heel area, for grass in the arch area. This points to an--up to now--unknown importance of the arch on unplain surfaces that are obviously influenced by the construction of the shoe and are not accessible by treadmill tests. The described different behaviour of shoes in treadmill and track and field tests points out the reduced validity of single treadmill tests.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1925927 TI - [Are stress fractures "hormone fractures"? On the current discussion of the cause of this sports injury]. AB - Discussion on the causes of stress reactions and/or stress fractures is at present under way. There are some pointers indicating that in women athletes this type of sports injury or damage is promoted by hormonal imbalance. Nevertheless, sports practice should always bear in mind that taking the "pill" cannot prevent stress damage. The primary cause is forced mechanical strain or load combined with improperly balanced training. The author makes specific reference to potentially dangerous types of training, and discusses these. PMID- 1925928 TI - [Stress reactions--stress fracture of the upper femoral neck in endurance sports]. AB - Stress reactions of the musculoskeletal system may be interpreted as possible precursors of stress fractures. Biological material, in contrast to artificial products, can react in numerous and complex ways. This can not only lead to a continual weakening of the tissue, but also to adaptation phenomena in response to overuse. The causes of such stress reactions are still unclear in many respects. For example, it is unknown to what extent a predisposition to these stress symptoms is created by mechanical stress alone or whether other factors such as physical condition, nutrition or even hormone balance come into play. Early diagnosis considerably reduces the healing process and, the later the diagnosis of the stress reaction, the more drawn out is the healing process and the extent of the athlete's absence from training. In this connection may be discussed whether the stress reaction can be the represent as the precursor of the stress fracture. In light of the need for taking special care in obtaining anamnestic data and determining the predisposition of an athlete, it appears to be justified to perform whole body bone scanning in the initial stages and particularly after an innocuous radiological finding. To what extent more current methods (e. g. MRI) can be applied without exposing the athlete to undue radiation cannot be conclusively judged at present. The treatment of a stress reaction should, at least at the beginning, be the same as for a diagnosed stress fracture. PMID- 1925929 TI - [Indoor hockey: injuries and prevention]. AB - Frequency and mechanisms of injuries in women's indoor-hockey are evaluated in a retrospective study of 89 players. Each athlete sustains 1.1 injury per season on the average. The goalkeeper's risk is about three times as high as that of the outfield players. The risk during match exceeds the risk during practice by a factor of 20. The most common site of injury is the lower limb (55%), 39% are related to the upper limb, 5% to head and trunk. Half of the lesions are caused by ball and stick, they involve especially hands and fingers. The facts allow to draw conclusions concerning preventive measures. The players must be protected by better equipment, special exercises and further development of the rules. PMID- 1925930 TI - [Stability after capsular ligament surgery of the knee joint]. AB - Post-operative checks of 57 cases of anterio-medial knee instability (II and III degree) were carried out over a period of 1-4 years after operation. "Subjective knee stability" was documented on three levels in a questionnaire as not "giving way". "Objective knee stability" was evaluated by measuring 30 degree anterior drawer displacement using the KT 1000 instrument. Strength of the thigh muscles of both legs for different power parameters under isokinetic load was measured with the Cybex II instrument system. No significant correlation between subjective perception of knee instability and instrumented measured anterior drawer displacement could be shown in a T-test. Individuals with higher "objective stability" or higher "subjective stability" level had both generally stronger tight muscle parameters, specially for knee extension. Most of our interest had the group of individuals assumed "subjective stable" but having quite a large anterior drawer displacement phenomena like ACL deficit knee. This group is characterized by higher 10 degree power parameters for knee extension and flexion and lower H/Q-quotient. This is supposed to be indication to functional adaptation of the neuro-muscular system to altered biomechanic situation after ACL disruption or reconstruction. Electromyographic studies should follow to test this hypothesis. PMID- 1925931 TI - [Nuclear magnetic resonance tomography and ultrasound imaging of anatomic structures of the shoulder joint]. AB - The possibilities of MRI and ultrasound in visualizing the structures of the shoulder joint are compared. Both methods have a good accuracy in detecting changes of the soft tissue of the shoulder. Changes of the cartilage and the bony structures are better seen in the MRI. The MRI gives a static and clear view of the shoulder joint, meanwhile the ultrasound depends on the dynamic examination. Ultrasound and MRI are both reproducible and non-invasive methods, who seem to complete one another at the examination of the shoulder. PMID- 1925932 TI - [Does performance of a stress roentgen image of the upper ankle joint in acute fibular capsule ligament lesion entail an operation? An experimental study]. AB - In an experimental study the sequelae of performing stress films on the ruptured lateral ligaments of the ankle joint are documented. It is shown that stress films may cause further damage on the ankle capsule when there is ligamentous disruption. After performance of stress studies a sufficient realignment of the interrupted ligaments by immobilization of the foot in a neutral (right angle) position can not be achieved. This makes, at least for younger patients, operative therapy after positive stress films advisable. PMID- 1925933 TI - [The value of adjuvant irradiation in patients with cervical carcinoma in histopathological stage Ib and negative lymph nodes]. AB - The present retrospective study attempts to evaluate the significance of adjuvant radiotherapy as a prognostic factor for stage Ib cervical carcinoma without lymph node metastases in addition to factors such as age, histological type, histological grading and tumor size. Between 1975 and 1987 224 patients were operated at our department or referred to postoperative radiotherapy and fulfilled the inclusion criteria: histopathological stage Ib, radical hysterectomy with pelvic lymphadenectomy and negative pelvic lymph nodes. The multivariate analysis confirmed that tumor size (tumor infiltration of the cervix greater than 2/3 vs less than 2/3: RR = 4.48) and histological grading (G3 vs G1 + G2: RR = 3.12) are significant prognostic parameters for survival. Postoperative adjuvant irradiation is a marginal significant factor for survival in stage Ib cervical carcinoma and negative nodes (RR = 3.22; p = 0.057). For women with negative nodes but high-risk prognostic factors in the cervix, a prospective randomized trial proving the value of postoperative irradiation would be of therapeutic interest. PMID- 1925934 TI - [The intracavity radiotherapy of cervical carcinoma with flexible applicators following the vesicovaginal interposition of the uterus]. AB - Advantages of new flexible intracervical applicators treating cervical cancer with high dose rate afterloading brachytherapy are reported: The insertion of the flexible applicator is usually possible without anesthesia and dilation of the cervix. Therefore the treatment can be performed on an outpatient basis. The risks of perforation and infection are minimal. Dosimetry and documentation of the applicator geometry are possible, if the planning system allows the definition of individual curves of an individual applicator. We now prefer flexible applicators instead of rigid steel applicators treating cervix carcinoma. PMID- 1925935 TI - [Metastasizing malignant meningioma: a case report]. AB - A case of metastasizing malignant meningioma is discussed concerning the etiology, clinical symptoms, diagnosis and therapy. The necessity of irradiation after surgery is turned out. Palliative treatment of bone metastasis is presented from an orthopedic point of view. PMID- 1925936 TI - [The radiation-sensitizing effect of isometronidazole following its intravesical application in bladder carcinoma. A clinical phase-II study]. AB - The radiosensitizing efficacy of iso-metronidazole, a 4-nitroimidazole derivative, was evaluated in a prospective clinical phase-II study. The results of combined radiotherapy of 25 patients with bladder cancer were compared with those of a control group of 25 patients treated with radiotherapy only. Tumor regression six months after radiotherapy was used as an endpoint. The surgical procedure was performed as double TUR. Evaluating the local tumor control after additional application of iso-metronidazole a gain factor of 1.2 is obtained. PMID- 1925937 TI - Dose estimation in postoperative keloid irradiation with special consideration of ovarian dose. AB - For a long time now, surgery followed by irradiation has been the preferred therapy in the treatment of keloids. Radiation can be administered by means of X rays (energy level less than or equal to 100 KV), electrons (energy level less than or equal to 5 MeV) or 192Ir wires. The choice of one of these methods depends on the availability of suitable facilities within a short period of time (less than 24 hours postoperatively), and the possibility of adapting the irradiation field quickly and easily to the scar. A further criterion is the dose received by underlying organs possibly, especially the ovaries of women of child bearing age. It consists of primary and secondary (scattered) parts of radiation and was measured in two standard field sizes for the various types of radiation so as to allow a rapid evaluation. Apart from the types of radiation mentioned above, such measurements were also carried out for 125I seeds. With a field size of 20 x 1.5 cm2 and a surface dose of 10 Gy, ovaries at a depth of 10 cm in the central beam will receive a dose of between less than 1 m Gy in electron therapy to around 1 Gy in X-ray therapy (100 KV). PMID- 1925938 TI - [The new development of an afterloading applicator for the primary treatment of endometrial carcinoma. The first clinical empirical report]. AB - Presented is a new afterloading applicator used for primary brachytherapy of endometrial cancer. The advantages: The afterloading applicator holds six afterloading tubes which bundled together in a cover. After the cover is pulled back, the individual tubes expand as a result of the sleeve shape and of the inherent stress of the plastic material used and make direct contact with the endometrium and with the tumor. The applicator is 8 mm in diameter which means that the cervix has to be dilated to Hegar 8 or 9. Radiation planning is done on the basis of orthogonal localisation X rays or MR. The newly designed applicator can be used for both HDR and LDR afterloading procedures. We have clinical experiences in 42 applications. PMID- 1925939 TI - Osteoblastic bone metastases in medullary thyroid carcinoma. AB - We report on a 32-year-old medullary thyroid carcinoma patient with extensive metastases at the time of diagnosis. In contrast to the osteolytic metastases usually observed in thyroid carcinoma, the patient had osteoblastic bone metastases, assumed to be caused by biologically active tumor calcitonin. The patient died 15 years after initial diagnosis of the advanced tumor. The long survival time may indicate that the prognosis is better for osteoblastic metastases than for osteolytic metastases. PMID- 1925940 TI - Biophysical aspects of the integrated combination of cytostatic drugs with radiotherapy. Part 3: In vivo investigations on murine C3H mammary adenocarcinoma treated with cis-platinum, adriamycin, epirubicin, activated cyclophosphamide, activated isophosphamide and irradiation with 10 MeV electrons--verification of the therapeutic results with 31P-NMR spectroscopy. AB - Radiobiological data referring to in vitro cell cultures proved to be adequate for the determination of an optimum sequence between drug incubation and consecutive irradiation, if the intracellular pH was subjected to accurate controls. An extension of the comparative study to the in vivo model of murine C3H mammary adenocarcinoma yielded synergistic effects, if the animals were treated with 10 MeV electrons and one of the drugs: cis-platinum, adriamycin, epirubicin, activated cyclophosphamide, activated isophosphamide. For comparative purpose the survey of the therapeutic results during and after finishing of the schedules was performed with 31P-NMR spectroscopy, radiometry (3H-thymidine) and a scanning system using 100 pH sensor microelectrodes. Although most extensive with regard to measurement technique, the latter method provided an accurate local pH distribution of a tumor tissue, while 31P only yielded the global pH value (average). PMID- 1925941 TI - The cornea and disorders of lipid metabolism. AB - Disorders of lipid metabolism, either hyperlipidemia or hypolipidemia, are associated with the formation of corneal opacities. Corneal arcus, the most commonly encountered peripheral corneal opacity, is frequently associated with abnormal serum lipid levels, but may occur without any predisposing factors. Reports also have linked corneal arcus with alcoholism, diabetes mellitus and atherosclerotic heart disease. Unilateral arcus is a rare entity that is associated with carotid artery disease or ocular hypotony. Diffuse corneal opacities associated with hypolipidemic disorders such as LCAT deficiency, fish eye disease and Tangier disease, may be the initial manifestation of these disorders and puts the ophthalmologist in a position to make an early diagnosis. Corneal arcus, along with a central corneal opacity, is seen in Schnyder's crystalline stromal distrophy. The association of the disorder with a dyslipidemia remains controversial. A review of lipid metabolism, corneal arcus and several disorders of lipid metabolism that affect the cornea are presented. PMID- 1925943 TI - Botulinum A toxin (Oculinum) in ophthalmology. AB - Botulinum A toxin has been used to treat strabismus and a variety of spasmodic neuromuscular diseases. Botulinum toxin treatment of strabismus is not as definitive and stable as the traditional surgical approach, but it has been found most useful in postoperative overcorrection, small deviations, sensory deviations, and acute sixth nerve palsy. This toxin has been effective in the treatment of essential blepharospasm and hemifacial spasm, for which it produces temporary relief of symptoms. In addition, this treatment has been applied to lower lid entropion, myokymia, aberrant regeneration of the seventh nerve, lid retraction, corneal exposure, nystagmus, spasmodic torticollis, and adductor spastic dysphonia. PMID- 1925942 TI - Systemic cholesterol microembolization syndrome masquerading as giant cell arteritis. AB - Two patients with clinical features consistent with giant cell arteritis were found to have systemic cholesterol microembolization syndromes. Diagnostic confirmation was established by a muscle biopsy in one patient and by a kidney biopsy in the other. Systemic cholesterol embolization can masquerade as a variety of disorders, including vasculitis, and should be considered in a patient with suspected giant cell arteritis who has a negative temporal artery biopsy. PMID- 1925945 TI - Optic atrophy. AB - A young woman became suddenly aware of visual loss in her left eye. She was found to have optic atrophy giving chronicity to the disease process. A hypopigmented macule on her face along with neuroimaging studies suggested an inflammatory process. A biopsy of the skin lesion was compatible with sarcoidosis. The patient responded to corticosteroid therapy. PMID- 1925944 TI - What to tell the patient with optic neuritis about multiple sclerosis. AB - If the ophthalmologist tells the patient with an initial isolated attack of optic neuritis that multiple sclerosis may develop, will he/she worry the patient needlessly or provide useful information that the patient is rightfully entitled to have? In this set of articles, the philosophies and individual circumstances that should influence the ophthalmologist in deciding what information to supply are discussed. PMID- 1925946 TI - The peripheral visual field in glaucoma: reevaluation in the age of automated perimetry. AB - With the advent of automated static perimetry has come the common practice of measuring only the central 30 degrees of vision in the diagnosis and management of glaucoma. While most glaucomatous field defects appear first in this portion of the visual field, the question remains as to how much useful information is being missed by ignoring the peripheral field, i.e., outside the central 30 degrees. Studies with both static and kinetic automated perimetry have revealed the same peripheral glaucomatous field defects previously recognized with manual perimetry, including generalized contraction, nasal steps, temporal sector defects, and hemianopic offsets. Of these, however, only measurement of the nasal periphery may add sufficient information to that obtained with static testing in the central 30 degrees to justify the added examination time; however, there are special situations in which peripheral field testing in other or all quadrants may be useful. Further study is required to establish optimum techniques for automated measurement of the peripheral visual field and to determine the significance of the results in the management of glaucoma. PMID- 1925947 TI - Pediatric ophthalmology and I. PMID- 1925948 TI - Early repair of selected injuries. PMID- 1925949 TI - Presidential address: all the King's men. PMID- 1925950 TI - Antrectomy with gastrojejunostomy for unresectable pancreatic cancer-causing duodenal obstruction. AB - The traditional approach to gastric outlet obstruction caused by unresectable pancreatic cancer is gastrojejunostomy performed during or after biliary bypass surgery. Previous work showed that gastrojejunostomy failed in 95% of patients with preoperative outlet obstruction, which was evidenced by nausea and vomiting. This study defines a better bypass procedure, namely, antrectomy with gastrojejunostomy, which was performed in 19 such patients. The cancer was primary pancreatic in 17 patients and metastatic to the pancreas in two patients with a renal and urinary bladder primary. All patients had duodenal extension with impaired alimentation. Fourteen patients underwent simultaneous biliary bypass surgery and antrectomy with gastrojejunostomy; the antrectomy with gastrojejunostomy procedure was performed in five patients 3 weeks to 6 months after biliary bypass surgery when duodenal obstruction supervened. Visible cancer extended to the duodenal stump in five patients, including two patients whose partial closure was buttressed with omentum. All 19 patients tolerated regular diet at the time of discharge 1 to 4 weeks after the antrectomy with gastrojejunostomy procedure. All patients, who died at 4 to 21 months after surgery tolerated solid food until immediately before death. All nine surviving patients have taken solid foods 9 to 29 months since the antrectomy with gastrojejunostomy procedure. We conclude that the antrectomy with gastrojejunostomy procedure, whether performed simultaneously with or subsequently to biliary bypass surgery, is the best palliative procedure for duodenal obstruction in patients with unresectable pancreatic cancer. PMID- 1925951 TI - Surgical management of BANS malignant melanoma. AB - Because melanomas of the upper back, posterior arm, neck, and scalp (BANS) have been shown to be at high risk for recurrence and metastases, a tendency is to carry out wide excision (WE) and elective radical node dissection (RND) for patients with such lesions. To investigate whether this regimen improves the survival rate, we reviewed retrospectively 62 patients with clinical stage I BANS melanoma. Forty-five patients were treated by WE alone and 17 patients were treated by WE and RND (WE + RND). The male:female ratio was 1.5:1 for WE and 1.8:1 for WE + RND. The mean age was 52.9 +/- 15.3 years for WE and 48.2 +/- 12.5 years for WE + RND (p = not significant [NS]). The overall survival rate at 1, 3, and 5 years was 98%, 76%, and 71% for WE and 100%, 88%, and 76% for WE + RND (p = NS). The disease-free survival rate at 1, 3, and 5 years was 91%, 76%, and 71% for WE and 100%, 88%, and 76% for WE + RND (p = NS). In conclusion, WE + RND does not improve survival of patients with stage I BANS melanoma. PMID- 1925952 TI - Breast biopsy with needle localization: influence of age and mammographic feature on the rate of malignancy in 350 nonpalpable breast lesions. AB - The purpose of this study was to determine the influence of mammographic feature and patient age on the rate of malignancy in nonpalpable breast lesions. During a 3-year period, 305 patients underwent biopsy after needle localization of 350 nonpalpable breast lesions. A total of 66 malignant breast tumors were found (biopsy yield rate, 19%): 23 carcinoma in situ, 43 infiltrating cancer. The biopsy yield rate in women younger than 50 years was 8% (12 of 153) and in women 50 years or older 27% (54 of 197; p less than 0.001). The biopsy yield rate varied with the mammographic feature in both groups of patients and was highest for spicular masses (61%), followed by strongly suspicious calcifications (29%). No cancers were found among well-defined masses or asymmetric densities. Other factors that were associated with high biopsy yield rate were personal or family history of breast cancer and diagnostic, rather than screening, mammography. The results suggest that the rate of malignancy in nonpalpable breast lesions is influenced by several factors, including age of patient and mammographic feature of the lesion. By taking all these factors into account, biopsies can possibly be performed more selectively thereby increasing the cost effectiveness of biopsy for occult breast cancer. PMID- 1925953 TI - The disease-free interval in breast cancer trials: scientific or spurious? AB - Reports that stem from the National Surgical Adjuvant Breast and Bowel Project clinical trials have had a major influence on the trend toward adjuvant chemotherapy. These reports use life-table analysis to report survival or disease free survival (DFS). DFS is reported more frequently than survival, and most studies report an increase in DFS with adjuvant therapy but no difference in survival. This means a shorter time between recurrence (end of DFS) and death. A conceptual model is presented herein with five possible explanations for this observation: (1) Bias exists in randomizing (entrance); (2) bias is introduced by the examining physician (exit end point); (3) the spectrum of micrometastases is selectively affected; (4) the sites of systemic recurrence (macrometastases) are affected; (5) treatment after recurrence (salvage) is less effective in the previously treated group; probably because of the induction of resistance to antineoplastic therapy. Hypothesis 5 seems most probable, and if so, the benefit of chemotherapy should be reserved for those women who need it rather than rendering everyone less treatable. The disease-free interval, with its doctor determined end point, is insufficiently reliable to be used for major decisions regarding adjuvant therapy. PMID- 1925954 TI - Recovery of neuromuscular function during reperfusion of the ischemic extremity: effect of mannitol and superoxide dismutase. AB - The ability of mannitol and superoxide dismutase (SOD) to improve the recovery of peripheral nerve and skeletal muscle function and to influence metabolism during reperfusion after 4 hours of complete ischemia was investigated in an autoperfused canine hind-limb model. Study groups included control subjects (n = 7), subjects given 5000 units/kg of SOD intra-arterial bolus immediately before reperfusion and 10,000 units/kg infusion during first hour of reperfusion (n = 7), and subjects given 150 mg/kg isosmolar mannitol intra-arterial bolus before reperfusion and 1 gm/kg intravenous infusion during the first hour of reperfusion. Function was evaluated by determining isometric twitch and tetanic contractile force of paw dorsiflexion by stimulating the peroneal nerve or the anterior tibial muscle. Metabolic responses (oxygen consumption and lactate clearance) and blood flow were not influenced by either treatment protocol. However, mannitol significantly reduced muscle damage and significantly improved neuromuscular contractile function compared to control and SOD treatment regimens. PMID- 1925955 TI - Management of dialysis-associated steal syndrome complicating upper extremity arteriovenous fistulas: use of intraoperative digital photoplethysmography. AB - Dialysis-associated steal syndrome (DASS) occurring after creation of arteriovenous fistulas often necessitates ligation of the fistula. From June 1987 to June 1990, a total of 542 upper extremity arteriovenous fistulas were constructed: radiocephalic fistulas in 182 patients, 325 forearm loop grafts and 32 upper arm loop grafts. We managed 27 patients with DASS including two patients who were referred from other hospitals. DASS developed in two patients (1%) with radiocephalic fistulas and in 23 patients (6.4%) with arteriovenous grafts. Of the 27 patients, the fistula was ligated in nine because of tissue loss, severity of symptoms, or absence of improvement in digital pressure with the fistula occluded. Intraoperative digital photoplethysmography was used to guide the amount of graft narrowing in 16 patients. The goal was to obtain a digital blood pressure of 50 mm Hg or digital to brachial ratio of more than 0.6. Ten of the 16 patients had satisfactory graft function for more than 6 months, and all patients had improvement or resolution of the steal syndrome. We conclude that DASS is an uncommon complication of upper extremity arteriovenous shunts and narrowing of the fistula and that using intraoperative digital photoplethysmography as a guide is a useful method for relieving the steal syndrome and salvaging the shunt. PMID- 1925956 TI - Comparison of serum and tissue antibiotic levels in diabetes-related foot infections. AB - Parenteral antibiotics are used as an adjunct to amputation or operative debridement for patients with diabetes who require emergency surgery for a septic foot. In 26 patients with a diabetes-related foot infection, one dose of various intravenous antibiotic regimens (gentamicin and clindamycin, ticarcillin/clavulanate, ampicillin/sulbactam) was administered during the hour before the procedure, and assays were performed to measure the antibiotic serum and tissue levels at the time of surgical debridement. Aerobic and anaerobic cultures were performed on infected tissue. The 172 bacterial isolates, including 95 aerobes and 77 anaerobes, (6.6 isolates per patient) underwent antibiotic susceptibility testing. Antibiotic levels were calculated by biologic assay from serum and tissue biopsies from the viable margins of the surgical site, which subsequently healed primarily or supported a split-thickness skin graft. Sixteen of the patients achieved therapeutic serum levels, and therapeutic tissue levels were reached in six patients at the time of surgery. A significantly lower number of patients had therapeutic tissue levels compared to serum levels (p less than 0.01, chi square). Initial intravenous antibiotic administration provides inadequate tissue concentrations for treating foot infections in patients with diabetes. Adequate serum antibiotic levels do not reflect therapeutic tissue antibiotic levels at the surgical margins in this group of patients. PMID- 1925957 TI - The effect of hypertonic saline resuscitation on bacterial translocation after hemorrhagic shock in rats. AB - Translocation of enteric bacteria occurs in rats after hemorrhagic shock. A proposed mechanism involves intestinal mucosal injury by hypoperfusion. Recent work suggests that moderate hypovolemia causes gut arteriolar constriction, which is ameliorated by hypertonic saline resuscitation. Bacterial translocation should, therefore, be reduced when hypertonic saline (HS) is used as the resuscitative fluid. Seventy-eight Sprague-Dawley rats were anesthetized and subjected to 30 minutes of hemorrhagic shock (systolic blood pressure 30 to 50 mm Hg) through a modified Wigger's model. Resuscitation was performed with either shed blood (B), 3% HS + 1/2B (1:1), or with 7.5% HS + 1/2B (1:1). Spleen, liver, and mesenteric lymph nodes were sent for quantitative culture 24 hours later. Translocation occurred if enteric organisms were cultured from at least one organ. Statistical analysis used the Fisher exact test. Compared to autotransfusion, hemodilutional resuscitation from hemorrhagic shock with hypertonic saline resulted in a significant reduction in bacterial translocation (p values were 0.03 and 0.04 for 3% and 7.5% hypertonic saline, respectively). The reduction in translocation after hypertonic saline resuscitation may be the consequence of microcirculatory alterations preventing gut hypoperfusion. PMID- 1925958 TI - Zollinger-Ellison syndrome in children: a 25-year follow-up. AB - The influence of gastric resection on the Zollinger-Ellison syndrome (ZES) in eight children was first reported to the Central Surgical Association 26 years ago. That report showed that the three children who had less than total gastrectomy were all dead with complications of gastric acid hypersecretion, although the five children who had total gastrectomy were living and well. During the past quarter of the century, the development of effective gastric acid inhibitors has prompted a greater emphasis on medical management in the ZES. The role of the surgeon and total gastrectomy remains controversial. Follow-up of the five young patients who had total gastrectomy shows that only one patient was dead with tumor 14 years after total gastrectomy and that the remaining four patients were alive 30, 29, 28, and 27 years, respectively, after total gastrectomy. Growth and activity have been near normal. All patients have had proven metastatic islet-cell carcinoma documented at some time in the course of the disease (lymph nodes in three patients and liver metastasis in two patients). Only one of the four living patients with total gastrectomy had a normal serum gastrin level and no apparent tumor. Gastrinoma tumor growth appears to be less aggressive in children than in adults. Complete excision of gastrinomas is possible in some patients with ZES. When hypergastrinemia persists, total gastrectomy may be preferable to lifelong medical management with gastric acid inhibitors in children and young adults with ZES. PMID- 1925959 TI - Carcinoma of the parathyroid gland: a 30-year experience. AB - Eleven patients with parathyroid carcinoma and 186 patients with parathyroid adenoma were seen between 1958 and 1990. Significant differences (p less than 0.01) were found between the two groups in calcium and parathormone levels, lesion size, presence of palpable mass, and severity of clinical presentation. Initial operative management consisted of parathyroidectomy alone in three patients, all of whom experienced recurrence of disease. Of the eight patients who underwent aggressive surgical management (parathyroidectomy and resection of thyroid or thymus), only one experienced recurrence. Three of the four patients with recurrence underwent multiple thoracic and cervical procedures for control of disease; one patient was treated with medical therapy alone. The mean survival in the surgical group was 17 years; the patient treated with medical therapy survived 10 years. In all four patients, however, treatment was palliative rather than curative. We conclude that patients with primary hyperparathyroidism characterized by markedly elevated serum calcium and parathormone, palpable mass, and severe clinical presentation should be suspected of harboring a parathyroid carcinoma. An aggressive initial surgical approach was considered in these patients. This experience emphasizes the importance of aggressive surgical extirpation in reducing disease recurrence and also for palliation and prolongation of life when recurrence does occur. PMID- 1925960 TI - Pancreatic ductal abnormalities in children. AB - From 1979 to 1990, 33 children required operative treatment for pancreatitis. Causes included ductal abnormalities (12 children), trauma (10 children), idiopathic (four children), gallstones (three children), drug-induced (three children), and tumor (one child). This study reviews the characteristics and outcome of the 12 children with ductal abnormalities. Symptoms were present up to 9 years or less before diagnosis, with two patients undergoing negative appendectomies. At diagnosis, amylase levels averaged 612 IU/L and lipase, 4761 IU/L. Preoperative studies included ultrasonography (11 children), endoscopic retrograde cholangiopancreatography (nine children), and computerized tomography (six children). Intraoperative cholangiopancreatography was performed in nine patients and was essential in four to diagnosis their anomaly. Patients were categorized into those with a common channel (three children), ampullary stenosis (two children), ductal fusion error (one child), or combinations (six children). Operations included sphincteroplasty (seven patients), pancreaticobiliary separation (six patients), pancreatic duct enterostomy (three patients), and distal pancreatectomy (one patient). Three patients required more than one procedure to repair the combination anomalies. Symptoms resolved immediately in nine patients. Two patients had delayed resolution, with one patient requiring the addition of somatostatin. One patient was lost to follow-up. Recurrent or protracted pancreatitis, without obvious cause, requires expeditious endoscopic retrograde cholangiopancreatography and/or intraoperative cholangiopancreatography. Operative therapy should be tailored to ductal anatomy and will resolve symptoms in most children. PMID- 1925961 TI - Late functional adaptation after colectomy, mucosal proctectomy, and ileal pouch anal anastomosis. AB - Ileal pouch-anal anastomosis (IPAA) is currently an alternative to proctocolectomy and ileostomy for patients with ulcerative colitis or familial polyposis. Some studies have suggested significant anal sphincter damage after mucosal proctectomy. Our aim was to assess prospectively late sphincter function after IPAA. In 250 patients, anorectal pressures were assessed with a pneumohydraulic perfused catheter manometry system. Each patient underwent colectomy, mucosal proctectomy, ileoanal anastomosis of a 15 cm ileal J-pouch, and loop ileostomy. Eight weeks after IPAA, anal manometry was repeated, and the ileostomy was closed. Manometry was repeated at yearly intervals. A decline in resting tone of the anal sphincter occurred early after IPAA with a gradual recovery toward control. External sphincter squeeze after pressures were not affected by IPAA and steadily increased to 8 years after operation. During this time, a progressive increase in J-pouch capacity was noted, and 24-hour stool frequency declined from 7.9 +/- 0.3 stools to 6.5 +/- 0.3 stools (p less than 0.05). We conclude that mucosal proctectomy results in internal anal sphincter trauma but is associated with long-term sphincter recovery, coupled with a significant improvement in external sphincter capacity, ileal pouch volume, and stool frequency. PMID- 1925962 TI - RS-61443 reverses acute allograft rejection in dogs. AB - RS-61443, a morpholinoethyl ester of mycophenolic acid, has been shown to prevent renal allograft rejection in dogs when administered in combination with low-dose cyclosporine and prednisolone. The purpose of this study was to test whether high dose RS-61443 can reverse acute renal allograft rejection. Mongrel dogs receiving a renal allograft were treated with baseline immunosuppression consisting of RS 61443 10 mg/kg, cyclosporine 5 mg/kg, and prednisolone 0.1 mg/kg. All animals developed acute allograft rejection. Dogs in group I (n = 11) received 14, 7, and 3.5 mg/kg methylprednisolone intravenously on 3 consecutive days after the diagnosis of rejection. Dogs in group II (n = 16) were given RS-61443 80 mg/kg twice daily. After rejection treatment, RS-61443 was increased to 20 mg/kg in all animals; cyclosporine and prednisolone were continued as before. In group I, five of 11 dogs developed uncontrollable rejection; in six of 11 dogs only a temporary reversal occurred. None of the dogs in group I survived for more than 20 days after the diagnosis of rejection. In group II rejection was completely reversed in 14 of 16 dogs (87.5%), resulting in a return of serum creatinine to prerejection levels. Thus, high-dose therapy with RS-61443 can successfully reverse acute kidney allograft rejection in dogs in a high proportion of cases. PMID- 1925963 TI - Fasted state impedes recovery of porcine hepatic oxygen consumption after warm hepatic ischemia. AB - The most effective means to prepare the hepatic donor liver for harvest, preservation, and transplantation are not known. Studies have shown that in combination with an injury to the liver, fasting reduces hepatic function. This study randomized 20 market pigs, 20 to 45 kg, to an overnight fast (fed group) or a 42-hour fast (fasted group). Under general anesthetic perfusion of the portal vein and hepatic artery were controlled. Studies were performed at high flow (30 ml/min/kg portal flow and 10 ml/min/kg arterial flow) and after a 90-minute period of warm ischemia (no flow). Flow was restored at 25% of the original (low flow), then increased to 50% of the original (medium flow). After the ischemic insult, the fed group improved hepatic oxygen consumption at a faster rate than the fasted group (p less than 0.05 by ANOVA). In addition, significant differences were noted between the fed and fasted groups in the amount of insulin delivered by the portal venous system to the liver (p less than 0.001 by ANOVA). Hepatic oxygen consumption was related to insulin delivery (r2 = 0.46; p less than 0.001) for both groups. The data suggest that acute changes in the nutritional status of both the donor and the recipient may affect hepatic recovery from ischemia. PMID- 1925964 TI - Ambulatory 24-hour esophageal manometry in the evaluation of esophageal motor disorders and noncardiac chest pain. AB - Standard manometry is currently considered the gold standard for the classification of esophageal motor disorders. We compared the new technique of ambulatory 24-hour esophageal motility monitoring to standard manometry in 108 patients thought to have a primary esophageal motor disorder, assessed the esophageal motor pattern associated with spontaneous noncardiac chest pain, and studied the effect of long esophageal myotomy on circadian esophageal motor function. Standard manometry was found to frequently overestimate and underestimate the severity of esophageal motor abnormalities as compared to 24 hour monitoring. Ambulatory manometry showed a direct correlation of abnormal esophageal motor activity with episodes of noncardiac chest pain in 13 of 26 patients who experienced the symptom during the monitoring period. The abnormal motor activity immediately preceding the pain episodes in these patients was characterized by an increased frequency of simultaneous, double and triple peaked, high amplitude, and long duration contractions (p less than 0.01). Long esophageal myotomy markedly reduced or eliminated the ability of the esophagus to produce these abnormal contractions (p less than 0.01). These data suggest that ambulatory esophageal motility monitoring allows more precise classification of esophageal motor disorders than standard manometry and identifies abnormal esophageal motor activity associated with noncardiac chest pain that can be abated by long esophageal myotomy. PMID- 1925965 TI - One-drug versus two-drug antibiotic therapy in pediatric perforated appendicitis: a prospective randomized study. AB - A prospective randomized study was undertaken to compare the use of the combination of gentamicin and clindamycin with single agent, cefoxitin, in the treatment of perforated appendicitis in the pediatric patient. In a 3-year period from 1986 to 1989, 56 patients with perforated appendicitis were randomized. Twenty-nine patients received cefoxitin, and 27 patients received gentamicin and clindamycin. Antibiotics were started before operation and continued for a minimum of 6 days after operation. Skin and subcutaneous tissues were left open at surgery and closed secondarily after day 3, if they appeared to be clean. Wounds were considered infected if they developed increased purulence with positive wound cultures. Age range was similar in both groups, with a mean of 9 years (range, 1 to 17 years); 28 were boys and 28 were girls. No changes in antibiotics were required for reasons of susceptibility. No adverse drug reactions occurred in either group. The most common organisms were Escherichia coli in 35 cases (62%) and Bacteroides species in 26 cases (46%). No difference was noted in infection complications in the two groups nor in length of hospital stay. Therefore, no difference is evident in the use of cefoxitin versus gentamicin and clindamycin in the treatment of perforated appendicitis in terms of disease or drug-related complications. PMID- 1925966 TI - Endoscopic treatment of postoperative biliary fistulae. AB - Postoperative biliary fistulae are difficult to manage, particularly in the face of obstruction or malignancy. We used endoscopic sphincterotomy or endoprosthesis placement to aide fistula closure in 52 patients with postoperative biliary fistulae. Thirty-seven patients with a fistula were treated with endoscopic sphincterotomy alone. Twenty-four of these 37 patients had a history of lithiasis; 21 patients were treated successfully by endoscopic sphincterotomy alone. The fistula closed in 2.4 +/- 1.6 days. Among the other 13 patients without history of stone disease, the fistula closed in seven cases (54%), 8.4 +/ 2 days after endoscopic treatment. Three patients ultimately required surgical intervention. In 15 patients an attempt was made to pass a 10F endoprosthesis above the fistula. Among the eight patients with successful prosthesis insertion, the fistula healed in six patients (75%). In the seven patients in whom a prosthesis could not be passed endoscopically, the percutaneous transhepatic approach was used. Surgical treatment (hepaticojejunal anastomosis) was ultimately required in two of these seven patients. Sphincterotomy alone is the preferred treatment for biliary fistulae-complicating surgery for gallstone disease. Alternatively, when a fistula is large, endoscopic placement of a prosthesis can be proposed as the first treatment. In cases of endoscopic failure, placement of a prosthesis through the percutaneous transhepatic approach is a useful alternative, particularly when the fistula source is located in the intrahepatic biliary tract. PMID- 1925967 TI - Endotoxin filtration and immune stimulation improve survival from gram-negative sepsis. AB - Polymyxin B, when bound to a polystyrene fiber (PMX-F), has been used experimentally as an extracorporeal blood filter to reduce serum lipopolysaccharide levels, which are believed to be responsible for physiologic alterations in the septic state. To validate our theory that a combination of PMX F, systemic antibiotics, and immune stimulation would improve survival, 78 rats were given intravenous doses of Escherichia coli (range, 4.6 to 6.2 X 10(8) colony-forming units/ml). They were then randomized into groups receiving either systemic gentamicin (n = 10); pretreatment with muramyl dipeptide (n = 11); or extracorporeal hemoperfusion through either a sham column (n = 8), PMX-F-packed column with systemic gentamicin (n = 8); or PMX-F-packed column with systemic gentamicin and muramyl dipeptide pretreatment (n = 8). Thirty-three control rats received no treatment. Sham hemoperfusion (13%) and control (21%) rats had the lowest survival rate, although increased improvement was noted in rats treated with gentamicin (30%) or the combination of PMX-F filtration and gentamicin (50%). The most significant improvements occurred in rats pretreated with muramyl dipeptide (53%) and in rats treated with a combination of PMX-F, gentamicin, and muramyl dipeptide (88%). These data show that lipopolysaccharide filtration and nonspecific immune stimulation are additive to antibiotic therapy and are useful as adjunctive measures in the multimodal treatment of experimental gram-negative bacterial infection. PMID- 1925968 TI - Gastric emptying of solids after Roux-en-Y gastrectomy: is extragastric vagal innervation important? AB - Truncal vagotomy, antrectomy with Roux-en-Y gastrojejunostomy is frequently complicated by poor gastric emptying. The aim of this study was to determine whether the vagal denervation beyond the stomach (extragastric vagal denervation) contributes to this delay in gastric emptying. Three groups of six female mongrel dogs underwent antrectomy, Roux-en-Y gastrojejunostomy, and either truncal vagotomy, gastric vagotomy, or no vagotomy. After operation each dog underwent two separate radioisotope gastric-emptying studies with a small volume solid meal. The dogs were scanned by a gamma-camera continuously for 4 hours, and images of the gastric remnant were summed by computer every 6 minutes. Radioactivity in the gastric remnant region of interest was compared to overall activity and plotted as a function of time. The half-emptying times (X +/- SEM) for each group were truncal vagotomy 164 +/- 24 minutes, gastric vagotomy 79 +/- 23 minutes, and no vagotomy 117 +/- 10 minutes. Animals with a gastric vagotomy had a significantly faster rate of gastric emptying than did those with truncal vagotomy (p = 0.02, Scheffe's test). Therefore the extragastric vagal innervation appears to play a role in determining the rate of emptying of solids after antrectomy and Roux-en-Y gastrojejunostomy. PMID- 1925969 TI - Use of technetium-labeled red blood cell scintigraphy in the detection and management of gastrointestinal hemorrhage. AB - The effectiveness of technetium 99m-labeled red blood cell scintigraphy in localizing hemorrhage, directing surgical intervention, and screening patients for arteriography was determined in 103 patients. The radionuclide scan result was compared to the bleeding site determined by arteriography, endoscopy, or surgery. Eighty-five patients had a bleeding site identified; 18 patients did not and were excluded. Thirty-one scans were performed in 29 patients for upper gastrointestinal hemorrhage. Five positive scans incorrectly localized an upper gastrointestinal bleeding site, although two scans localized the site, for a scan sensitivity of 8%. Fifty-nine scans were performed in 56 patients with lower gastrointestinal bleeding. Fifteen scans were positive, three incorrectly localizing the hemorrhage. Seventy-four percent of the patients with lower gastrointestinal hemorrhage documented by arteriography, endoscopy, or surgery had negative scans for bleeding. The radionuclide scan sensitivity for lower gastrointestinal bleeding was 23%. Surgery was required in 18 patients for bleeding, 11 of whom had negative scans for bleeding. In seven surgical patients with positive scans, in no instance did the scan direct the surgical intervention. Eighteen patients underwent scintigraphy and arteriography; nearly one half of the patients with negative scans for bleeding had positive localizing arteriograms, although almost one half of the patients with positive scans for bleeding had negative arteriograms. Scintigraphy failed to localize hemorrhage in 85% of the patients. Technetium 99m-labeled red blood cell scintigraphy did not direct surgical intervention, nor did it adequately screen patients for arteriography. PMID- 1925970 TI - Calcitonin gene-related peptide in the amygdaloid complex of the rat: immunohistochemical and quantitative distribution, and drug effects on calcium dependent, potassium-evoked in vitro release. AB - The amygdaloid complex is an area with a high concentration of calcitonin gene related peptide. In the present paper, immunohistochemical studies revealed a dense innervation of the central nucleus originating most probably from the bed nuclei of the stria terminalis. For determination of tissue concentrations of calcitonin gene-related peptidelike immunoreactivity, the amygdaloid complex was dissected into four parts. The distribution was found to be uneven with the highest concentration (1153.3 fmol/mg protein) in the portion including the nucleus amygdaloideus centralis. High performance liquid chromatographic analysis from an extract of amygdaloid tissue showed that 97% of the calcitonin gene related peptidelike immunoreactivity measured by radioimmunoassay is authentic rat calcitonin gene-related peptide alpha or beta. Release of calcitonin gene related peptidelike immunoreactivity was measured in superfused slices of amygdalae pooled from three rats. High potassium (60 mM) caused a significant release of calcitonin gene-related peptidelike immunoreactivity (from 0.88% of total tissue content to 1.91%) from the amygdaloid complex in vitro, which was blocked in calcium-free buffer. Pretreatment with haloperidol or clozapine caused a significant reduction of the 60 mM potassium-evoked release, compared with a saline treated control group (control 21.0 fmol; haloperidol 2.8 fmol; clozapine 8.8 fmol) and an increase of tissue levels after haloperidol treatment by 43%. These results demonstrate that calcitonin gene-related peptide is integrated in amygdaloid functions and possibly a target for actions of neuroleptic drugs. PMID- 1925972 TI - The new Dental Practice Act in Texas: some ramifications for the practitioner. A two-part series. PMID- 1925971 TI - The effect of the acetylcholine transport blocker vesamicol on central cholinergic pressor neurons. AB - Vesamicol (AH5183) inhibits the uptake of acetylcholine into cholinergic neuronal storage vesicles. Earlier in vitro studies have demonstrated that such inhibition can lead to a failure of transmission, particularly in peripheral cholinergic tissues. The present study was designed to determine whether vesamicol could inhibit central cholinergic transmission in conscious freely moving rats. Central (lateral cerebroventricular) injection of 20 micrograms of vesamicol significantly reduced the hypertensive and bradycardic response to subsequent central injection of physostigmine in spontaneously hypertensive rats. Inhibition of the pressor response was greatest when physostigmine was administered 1 hr after vesamicol. Acetylcholine and choline levels were determined in three brain regions derived from rats treated one hr earlier with either vehicle or vesamicol. Acetylcholine levels were found to be unaltered after vesamicol treatment, although choline levels were significantly higher in two brain regions. These results are consistent with the ability of vesamicol to inhibit the function of central cholinergic cardiovascular regulatory neurons. The mechanism for this inhibition is not related to depletion of total brain acetylcholine content but may be due to depletion of a small critical pool of transmitter. PMID- 1925973 TI - Medical sonography: reproductive effects and risks. AB - While it is clear that the levels and types of medical sonography that have been used in the past have no measurable risks, it would be inaccurate to label the modality of ultrasound as totally safe regardless of exposure. Most agents have reproductive risks and even teratogenic risks if the exposure is raised sufficiently. Thus the prudent use of sonography means that clinicians and designers of equipment have to maintain exposures far below the risks that have been demonstrated in animal studies and from the knowledge obtained about the physical changes that can be produced in humans as the absorbed dose is elevated. The reproductive risks were evaluated using five criteria: 1) human epidemiology, 2) secular trend data, 3) animal experiments, 4) dose response relationships, and 5) biologic plausibility. The analysis reveals that the human epidemiology does not indicate that diagnostic ultrasound presents a measurable risk to the developing embryo or fetus. Animal studies also indicate that diagnostic levels of ultrasound are safe and do not elevate the fetal temperature into the region where deleterious embryonic and fetal effects will occur. Because higher exposures of ultrasound can elevate the temperature of the embryo, the use of diagnostic procedures and the design of sonographic equipment should take into consideration the hyperthermic potential of higher exposures of ultrasound and the hypothetical additional risk of performing sonography on pregnant patients who are febrile. It would appear that if the embryonic temperature never exceeds 39 degrees C, then there is no measurable risk. We suggest that sonography (the field) and sonogram (the procedure) are the most appropriate and least anxiety provoking terms. PMID- 1925974 TI - Permanent neuronal deficits in rats exposed to alcohol during the brain growth spurt. AB - The purpose of this study was to determine whether developmental alcohol exposure could induce permanent neuronal deficits, whether the peak blood alcohol concentration (BAC) influences the severity of the effects, and whether the effects are gender related. Rat pups were reared artificially over postnatal days (PD) 4 through 11 (a period of rapid brain growth, comparable to part of the human third trimester). Alcohol treatments were administered on PD 4 through 9. Patterns of alcohol exposure that produce different peak BACs have been shown to affect differentially the amount of brain weight deficits and neuron loss shortly after the exposure period, so this study investigated whether the pattern of alcohol exposure was also effective in producing permanent deficits. Two groups received a daily alcohol dose of 4.5 g/kg, condensed into either four or two feedings. A third group received a higher daily alcohol dose of 6.6 g/kg administered in 12 uniformly spaced daily feedings. Pups were fostered back to dams on PD 11 and perfused on PD 90. Brain weights were measured, and Purkinje cells and granule cells were counted in each of the 10 lobules of the cerebellar vermis. In the hippocampal formation, cell counts were made of the pyramidal cells of fields CA1 and CA2/3, the multiple cell types of CA4 and the granule cells of the dentate gyrus. The groups receiving the lower daily dose (4.5 g/kg) condensed into either four or two feedings were exposed to higher peak BACs and suffered significant permanent brain weight deficits and neuronal losses, relative to controls. The group receiving the higher daily dose (6.6 g/kg) in continuous fractions had no significant brain weight reductions or neuronal loss. Vulnerability to alcohol-induced neuronal loss varied among regions and cell populations and as a function of peak BAC. In the hippocampus, only the CA1 pyramidal cells were significantly reduced in number and only in group receiving the most condensed alcohol treatment. In the cerebellum, the severity of Purkinje cell and granule cell losses varied among lobules, and Purkinje cell vulnerability appeared to depend on the maturational state of the neuron at the time of the alcohol exposure, with the more mature Purkinje cells being the more vulnerable. PMID- 1925975 TI - Development of the lung in mice with bromodeoxyuridine-induced cleft palate. AB - Clinical and laboratory observations show that denial of free communication between the amniotic fluid and lung fluid results in pulmonary hypoplasia. Thus, cleft palate resulting from tongue obstruction to palatal shelf elevation might be associated with disturbed lung development. This association exists in the Pena-Shokeir phenotype. The goal of these experiments was to see what effect bromodeoxyuridine (BUdR)-induced cleft palate had on lung development. LACA mice were injected with 500 mg/kg BUdR on E11 or E11 and E12 of gestation, a treatment known to produce a 25% and 50% incidence of cleft palate, respectively. BUdR had a direct retarding effect on lung growth but, when cleft palate occurred as well, the lungs were more severely affected. Morphometry showed that lungs from fetuses with cleft palate had only one-half the saccular volume of controls or of treated fetuses with normal palates. Although hypoplastic, lungs associated with cleft palate had type I and type II pneumocytes, and the latter were shown by electron microscopy to be capable of producing surfactant. Hence, cellular differentiation had not been affected by the treatment. Fetuses with cleft palate had less amniotic fluid than controls but significantly more than those with normal palates after treatment. Thus, the pattern of abnormalities in this animal model bears some resemblance to that of the human Pena-Shokeir phenotype. PMID- 1925976 TI - Bias in congenital malformations information from the birth certificate. AB - An analysis of 1983 data from California birth certificates, and from the California Birth Defects Monitoring Program case registry, showed that there is a bias in reporting of congenital malformations on the birth certificate. Hospitals with many births erroneously report lower malformation rates than do hospitals with few births. The bias is partly due to the source of information; larger hospitals are more likely to get their information about malformations from the obstetrician than from the pediatrician. Since malformation data recorded on the birth certificate is both incomplete and biased, at present it is advisable to use these data for epidemiologic analyses with great caution. PMID- 1925977 TI - Ultrastructure and function of the rat yolk sac: damage caused by teratogenic anti-VYS serum and recovery. AB - It was hypothesized that heterologous anti-rat visceral yolk sac serum (AVYS) exerts its teratogenic effect by reducing the endocytosis of serum proteins by the visceral yolk sac (VYS), thus reducing the supply of amino acids to the embryo and VYS. To evaluate this hypothesis, we studied the effect of teratogenic AVYS on the endocytic function of the VYS and the ultrastructure of the VYS and parietal yolk sac (PYS). Rat conceptuses were exposed to a teratogenic dose of AVYS on the 10th day of gestation in vivo or in vitro. Control and AVYS-exposed specimens were collected 24-192 hr later and prepared for scanning and transmission electron microscopy (SEM and TEM, respectively) utilizing standard procedures. The Endocytic Index was calculated for the VYS utilizing standard procedures. Approximately 97% of the in vivo exposed and 94% of the in vitro exposed embryos were morphologically abnormal. Ultrastructural observations showed that exposure to AVYS in vivo or in vitro caused severe damage to the VYS endodermal epithelial cells with loss of cellular borders, reduction in the number and length of microvilli, and increased cellular inclusions; and some damage to PYS endodermal cells with increased blebbling and decreased cell number. Recovery was evident at 72 hr and complete by 96 hr. The Endocytic Index was significantly reduced in the VYS 24 and 48 hr after injecting AVYS into the pregnant rat but was not significantly different at 96 and 192 hr. Our results show that the AVYS antiserum damaged visceral endodermal epithelium experienced ultrastructural recovery with parallel functional recovery. These studies suggest that transient yolk sac placental ultrastructural damage and dysfunction was probably sufficient to cause irreversible damage to the developing embryo during early organogenesis. We conclude that the proximate effect of the AVYS was on the plasma membrane of the visceral endoderm and that decreased pinocytosis is a consequence of this effect. PMID- 1925978 TI - Effects of in vivo exposure of pregnant hamsters to glucose. 1. Abnormalities in LVG strain fetuses following intermittent multiple treatments with two isomers. AB - The increased frequency of congenital malformations including caudal regression syndrome, in infants of women with insulin-dependent diabetes mellitus is well documented. Most of the related animal research has involved the in vitro embryo culturing methodology. This study involved the alternative in vivo approach in order to determine the effects of treatment of pregnant hamsters with the D- and L-isomers of glucose at five times just before and during the period of embryonic organogenesis on maternal blood glucose levels and the rates and types of fetal abnormalities. One group of animals was injected with 5 doses (4 g/kg each) of D glucose, i.e., on gestation day (D) 6, 3 PM; D7, 8 AM and 3 PM; D8, 8 AM and 3 PM. Two other groups were treated the same way but with L-glucose (4 g/kg per dose) and water (10 ml/kg per dose), respectively. The D-glucose treatment produced alternating periods of hyperglycemia and normoglycemia in the pregnant hamsters, enlarged placentae and fetuses with small urinary bladders, microphthalmia and skeletal abnormalities of the sternum, caudal vertebrae, pelvic bones, and femora. The L-glucose treatment did not produce changes in maternal blood D-glucose levels but did produce fetuses with small urinary bladders, microphthalmia and abnormal ossification limited to the manubrium. Several interpretations of the D-glucose-induced fetal abnormalities involving the vertebrae, proximal hindlimb bones and urinary bladders are discussed, including the consideration that this cluster has interesting similarities to the spectrum of skeletal and soft tissue abnormalities of human diabetes-related caudal regression syndrome. PMID- 1925979 TI - Developmental regulation for collagen II gene expression in transgenic mice. AB - In order to evaluate the involvement of the type II collagen regulatory sequences in development, we have injected a construct containing a toxin gene under the control of the rat type II collagen promoter and enhancer. The construct, pDAS10 DTA, contained the diphtheria toxin A chain gene under the control of type II collagen sequences which had been used previously to target cartilagenous tissues in transgenics. Inspection of developing fetuses at various stages of gestation revealed a high number of aborted implants as well as abnormally developing fetuses. These abnormal fetuses were of small size, had shortened and underdeveloped limbs, cleft palates, and generally resembled a phenotype similar to chondrodystrophic mice. Histological comparisons of normal and abnormal fetuses indicated a reduced amount of extracellular matrix surrounding chondrocytes, and a disorganized appearance of the tissue. These results suggest that the expression of the toxin has occurred in chondrocytes and altered the survival and development of the transgenic mice. These results also indicate that the promoter and enhancer sequences contained in the transgene controlled the developmental expression of the type II collagen gene expression. PMID- 1925980 TI - Involvement of the intestinal microflora in nitrazepam-induced teratogenicity in rats and its relationship to nitroreduction. AB - A study was undertaken to investigate the relationship between nitroreduction of nitrazepam and its teratogenic effects and the involvement of the intestinal microflora in Sprague-Dawley rats. Incubation of bacterial suspensions from rat cecal contents with nitrazepam resulted in extensive reduction to 7 aminonitrazepam. Rat liver homogenates also reduced nitrazepam but only under anaerobic conditions. Following oral administration of 300 mg/kg nitrazepam to pregnant rats, total excretion of reduced metabolites (7-aminonitrazepam and 7 acetylaminonitrazepam) in urine and feces accounted for approximately 30% of the administered dose. When antibiotics were administered to dams to deplete their intestinal microflora prior to administration to nitrazepam, the total excretion of the reduced metabolites in the urine and feces decreased to 2% of the dose. Nitroreductase activity of cecal contents was almost completely suppressed by antibiotic pretreatment, but the activity of liver homogenates was not significantly altered by the same treatment. The incidence of nitrazepam-induced malformations was markedly decreased by antibiotic pretreatment. These results suggest that the intestinal microflora plays an important role in the reductive metabolism of nitrazepam and that the teratogenicity of nitrazepam may be related to its nitroreduction by the microflora. PMID- 1925981 TI - Relationship between fetal weight and malformation in developmental toxicity studies. AB - Exposure to developmental toxicants may cause fetal malformations, increase prenatal death rates and reduce fetal weight at term. However, there has been little formal study of the relationship among these effects. Certainly, no statistical methods are currently available to jointly analyze these effects of exposure. As a preliminary step in developing such methods, simple exploratory analyses were conducted using a series of ten studies conducted for the National Toxicology Program. Because fetal weight and malformation status were both reported for all live fetuses, the data permitted an exploration of the correlation between these two outcomes. The data show a clear pattern wherein malformed fetuses tended to be lighter at term than nonmalformed fetuses. While these patterns cannot be used to draw inferences regarding the biological relationship between fetal weight and malformation, they do suggest the potential value in developing statistical models for the joint effect of exposure on fetal weight and malformations. PMID- 1925982 TI - Normal mouse strains differ in the site of initiation of closure of the cranial neural tube. AB - The scanning electron microscopic study of day 9 embryos reported here documents differences among normal mouse strains in morphology of cranial neural tube closure. The site of initiation of contact and fusion of the cranial neural folds, previously defined as Closure 2 (Macdonald et al., '89), is located in the region of the junction between the forebrain (prosencephalon) and midbrain (mesencephalon) in three normal strains: LM/Bc, AEJ/RkBc, and ICR/Bc. However in a fourth normal strain, SWV/Bc, Closure 2 is initiated much further rostral, in the prosencephalic region. In addition, the anterior neuropore, rostral to Closure 2, closes late in ICR/Bc embryos, relative to the posterior progress of development of the Closure 2 seam. Initiation of closure from the most rostral end of the neural tube (Closure 3) appears to be relatively delayed in ICR/Bc embryos. We hypothesize that the observed genetic polymorphism in location of the first site of fusion between the cranial neural folds in normal mouse embryos may be one basis for differences among normal strains in liability to exencephaly induced by teratogens. PMID- 1925983 TI - Payment reform and HIV issues dominate AMA meeting. PMID- 1925984 TI - Short-sighted politics undermine physician payment reforms. PMID- 1925985 TI - Behind the scenes at the PPRC: what happened to 'fair' and 'equitable'? PMID- 1925986 TI - The HCFA perspective: continued dialogue is vital. PMID- 1925987 TI - Texas: one of the biggest RBRVS losers? PMID- 1925988 TI - The Medicare fee schedule: like it or not, here it comes. PMID- 1925989 TI - Ties that bind? The web of CME and medical industry profit. PMID- 1925990 TI - Gag order represents serious intrusion into medical matters. PMID- 1925991 TI - OIG fraud alert: cracking down on charity or crime? PMID- 1925992 TI - The physician's guide to medical waste regulations. PMID- 1925993 TI - Relief! A legislative end to UR abuse. PMID- 1925994 TI - Speaking of Medicaid hassles... PMID- 1925995 TI - Cholera: is Texas at risk? PMID- 1925996 TI - The hazards of mandatory HIV testing of physicians. PMID- 1925997 TI - Data-based interventions for cancer control in Texas. AB - The percentage of excess mortality based on the ratio of the race-ethnic-sex specific regional rate to the state rate was used to identify regions with differing risks of lung, breast, and cervical cancer. Mortality maps show wide variation in mortality risks for these cancers not only by race and ethnicity but also by geographic region. Cancer-staging information from the State Cancer Registry indicated that excess mortality for breast and cervical cancers in black and Mexican-American women results largely from the later detection of these cancers. Together with geographic mapping of data on cancer mortality, data on the prevalence of tobacco use and on the use of Papanicolaou's tests and mammograms can be used to select and direct interventions to specific regions and to the highest risk populations. Evaluation of routinely collected cancer data, particularly in state health departments, is a primary step in implementing programs to control and prevent cancer in Texas. PMID- 1925998 TI - The "incompleat" physicians: community physicians' lack of knowledge of medical socioeconomics and politics. AB - The suspicion that physicians in this community know little about current events in American medical socioeconomics and politics led to a survey of the local medical society membership. The results showed a discouraging lack of knowledge about information that is readily available to physicians. We concluded that current methods for educating physicians in these subjects are largely ineffective. Live, as opposed to printed, presentations at local, state, and specialty medical society meetings may be more effective in educating, and thereby involving, physicians in the critical political and economic issues presently facing them. PMID- 1925999 TI - Psychiatric hospitalization of children and adolescents. AB - Legislative funding and class action suits have impinged in many ways on the delivery of psychiatric service in Texas. In recent years, the rate of psychiatric hospitalization for youth has decreased in the public sector. Does the increased rate of child and adolescent psychiatric care in private hospitals reflect a need for this care or is it an excessive level of care? The prevalence of psychiatric disorders in youth has been determined, and planners of mental health services have this information. The heated rhetoric about whether or not these youth need to be hospitalized obscures the real issue: many children and youth do not receive the mental health care that they need, and this lack of care affects every level of intervention. PMID- 1926000 TI - [Benign and malignant intestinal diseases]. PMID- 1926001 TI - [Colorectal diseases: diagnosis]. AB - Colonoscopy is now the accepted diagnostic procedure for most colorectal diseases, although studies comparing sensitivity and specificity of double contrast barium enema with total colonoscopy or combined procedures such as sigmoidoscopy and same-day double-contrast barium enema versus colonoscopy are still being performed. For diagnosis of diverticulitis and fistulas, however, barium enema is still the diagnostic procedure of first choice. Several studies have demonstrated a high sensitivity and specificity for ultrasonography in diagnosis of appendicitis. It seems that the number of unnecessary laparotomies in suspected appendicitis can be reduced by ultrasonography. In rectal carcinoma the therapeutic procedures are determined by the grade of local tumor infiltration and by tumor invasion of local lymph nodes. To predict the tumor stage, rectal endosonography has become the most reliable method. New genetical tests have been developed to diagnose presymptomatic stages in persons at risk of family adenomatous polyposis. PMID- 1926002 TI - [Colonic polyps: clinical and practical implications]. AB - Among colorectal polyps, various forms of neoplastic or non-neoplastic lesions are distinguished by histology. Most accumulated knowledge suggests that the majority of cancer of the colon arise in pre-existing benign neoplastic polyps (adenoma-carcinoma sequence). Because of the risk of cancer being already present, all adenomatous polyps must be removed in toto. The carcinoma may occupy only a small area of the polyp, and therefore, forceps biopsies are inappropriate due to the sampling error. Since patients with polyps detected by rectosigmoidoscopy often have further polyps in the remaining part of the colon, complete examination of the whole colon is required. Follow-up examinations are indicated, because the risk of developing new polyps is high. Studies of the life history of the adenoma-carcinoma sequence suggest that interval of complete large bowel follow-up may be about 5 years. The policy of polypectomy and follow-up examinations should be possible to prevent the development of colorectal cancer. PMID- 1926003 TI - [Colorectal cancers: surgical therapy]. AB - Successful treatment of colorectal cancer is still founded on surgical resection. Therefore the indication for an operative treatment is generally given. During the last years surgical improvements were especially made in sphincter-saving procedures of the rectum. Although improvement in anaesthetic methods and perioperative care have reduced operative mortalities, the reports of the overall five-year survival rates are not very encouraging and essentially depend on the primary tumor staging. Unfortunately 10 to 25% of the potentially curable patients develop local recurrence within two years of operation. PMID- 1926004 TI - [Colorectal cancers: adjuvant therapy and after care (including tumor markers)]. AB - Perioperative adjuvant treatment after radical surgery for colorectal cancer has proven to be possible without an increase of postoperative complications and postoperative mortality. In overcoming this surgical fear, a number of randomized studies, all of them investigating the role of adjuvant treatment, have been initiated. Preliminary results of these trials show, some of them already statistically significant, an advantage of the adjuvant treated patient group. Unless these results have been confirmed, adjuvant treatment should only be given in well designed, randomized clinical trials. Only these trials can prove the effectiveness of adjuvant therapy in radical surgery of colorectal neoplasms. In addition, these studies should be used to define the group of patients who really benefit of adjuvant treatment. The main goal of follow up methods after surgery for colorectal cancer should be the detection of asymptomatic and still treatable tumor recurrences. For this reason, frequent clinical investigations and frequent CEA level determinations seem to be the most important components at this time. PMID- 1926005 TI - [Colorectal cancers: therapy of recurrences and metastases]. AB - Recurrent disease from colorectal carcinomas is common. 25 percent of patients have apparent metastases at the time of first detection of the tumor, and at least 50% of patients die from their tumor. The aim of the postoperative follow up of patients with carcinoma of the colon and rectum is thus to detect recurrent tumor when cure is still possible. Clinical examination and CEA-measurement is widely recommended as a reliable indicator for recurrence and metastases of colonic cancer. This may be combined with regular coloscopic surveillance for detection of anastomotic recurrences or a second colonic cancer. In case of suspicion of a recurrence or metastasis a full range of examinations should be performed to detect the site of recurrent tumor and to exclude wide spread disease. In case of a circumscribed lesion the patients may benefit from local radical resection. Patients with four or less unilateral liver metastases show a five year disease free survival reported of more than 30% and a disease free survival reported of more than 25%. Unfortunately because of wide spread misunderstanding of the potential of hepatic Rx only about 1/3 of potentially curatively resectable patients with liver metastases finally undergo liver surgery. A more active policy towards patients with colorectal disease concerning surveillance may lead to a better survival in selected cases. PMID- 1926006 TI - [Inflammatory bowel diseases: conservative therapy]. AB - Recent advances in the medical treatment of the inflammatory bowel diseases are reviewed with emphasizes on controlled clinical trials. The newly developed mesalazine contains the active moiety of sulfasalazine, the 5-aminosalicylic acid. In ulcerative colitis mesalazine appears to be as efficacious as the time honored sulfasalazine; it has however less adverse effects. Corticosteroids remain the most effective drugs in severe attacks of all forms of inflammatory bowel diseases. The immunosuppressive agents 6-mercoptopurine and azathioprine are useful second-line drugs in otherwise refractory Crohn's disease. The place of cyclosporin is at present uncertain. Metronidazole is the only efficient antibiotics in the treatment of Crohn's disease. The relative merits of various diets are discussed. PMID- 1926007 TI - [Inflammatory bowel diseases (Crohn disease and ulcerative colitis). Possibilities and limitations of surgical therapy]. AB - Ulcerative colitis can be cured by surgical therapy. Indications for surgery are severe disease not controlled by medical therapy, complication of colitis and prophylaxis of malignancy. Operation of choice is proctocolectomy and ileoanal anastomosis with pelvic ileal pouch, preserving continence. Alternatives are colectomy and ileo-recto-anastomosis if the rectum is free of disease and proctocolectomy with ileostomy if the rectum is involved. Crohn's disease cannot be cured by surgery. Indications for surgery are obstructing or perforating complications of enterocolitis. Basis of surgical therapy is resection, which should be restricted to the severely diseased bowel segment. Structureplasty can correct short bowel stenosis without resection. Surgery for anal Crohn's disease should be limited to drainage of septic complications. Postoperative results support a tendency towards early surgery in ulcerative colitis, while surgery in Crohn's disease should be reserved for severe and complicated disease. PMID- 1926008 TI - [Diverticular disease: When to operate?]. AB - We present our experience with 431 patients suffering from diverticular disease. Indications for emergency and elective surgery are given. Immediate laparatomy is mandatory for severe diverticular bleeding, bowel obstruction and sigmoid perforation. Aggressive surgical management is appropriated for purulent and fecal peritonitis. Resection of the perforated sigmoid colon by the Hartmann procedure is the method of choice and helps to reduce mortality markedly. A resection with primary anastomosis can be performed in equal safety if there is only a localised peritonitis. One stage resection is most frequently performed for elective cases with recurrent attacks and bleeding, painful or obstructing diverticular disease, fistula and if a cancer cannot be excluded. Aggressive surgical treatment helps to lower mortality and morbidity and is the best tool in prevention of severe complications for diverticular disease. PMID- 1926009 TI - [Motility of the large intestine: from irritable colon to obstipation]. AB - The investigation of colonic motility is a difficult task. Little is known on the myoelectrical activity of the human colon or on physiologic manometric findings. Scintigraphic studies have been performed to investigate the movement of colonic contents and have revealed that the ascending colon mainly acts as a storage area. Because physiologic data are rare, the interpretation of findings in patients with distinct bowel symptoms may be very difficult to interpret. Only a part of the patients who present with chronic obstipation have colonic inertia which is characterized by a slow transit through the entire colon. Other patients may have anismus, i.e. a disturbance of the highly complex activity of defecation. Elderly patients may have diminished rectal sensitivity to dilation and thus do not feel the urge the defecate. Patients with irritable bowel syndrome have been extensively investigated for underlying motility disorders. In spite of ample data the exact pathogenesis remains unknown. Furthermore, it has become clear that patients with the irritable bowel syndrome not only have irritable guts but also an irritable personality. Treatment of chronic constipation is difficult. Bulking agents and osmotically active laxatives often fail to give a satisfactory result. Patients with irritable bowel syndrome may benefit from both bulking agents, but tranquilizers may be helpful as well. PMID- 1926010 TI - [Acute intestinal hemorrhage: a diagnostic and therapeutic challenge]. AB - Bleeding per anum is a common medical-surgical problem. The severe acute intestinal bleeding is rare and concerns mostly elderly patients. Localizing active sites of bleeding within the intestine remains a difficult diagnostic and therapeutic task. The most frequent reasons of acute intestinal bleeding in elderly patients are diverticula, angiodysplasia and tumors. In younger patients the site of bleeding is usually a Meckel diverticulum. Endoscopy, angiography and scintigraphy allows generally to avoid blind resections. The possibility of an exact localization of a bleeding site permits a local therapy by the way of endoscopy or surgery. PMID- 1926011 TI - [Collagen colitis--a clinical entity of relevance]. AB - Collagenous colitis is a clinical and pathological entity characterized by chronic watery diarrhea and deposition of collagen beneath the surface epithelium of the large intestine. By colonoscopy and barium enema the colon appears normal. The laboratory tests give usually normal results. 75% of the patients are middle aged women with a mean age around 50 years. The etiology of the disease is still unknown. An association with various autoimmune diseases has been suggested, but was never proven. Up to now, it is not clear whether the collagenous colitis is a distinct entity or only an epi-phenomenon of another disease which leads to thickening of the collagen layer. Collagenous colitis is diagnosed if all other diseases with chronic watery diarrhea are excluded. A specific treatment is not known. Symptomatic treatment with bulk and antidiarrheal drugs improves the symptoms of most of the patients. PMID- 1926012 TI - [Antibiotic-associated colitis--the dark side of antibiotic therapy]. AB - Intestinal side effects after antibiotic therapy are frequent. Mostly, harmless diarrhea disappears after cessation of therapy without inducing colitis; however, changing of the intestinal flora sometimes leads to colonization of the colon by toxin-producing strains of Clostridium difficile, inducing sometimes severe pseudomembranous colitis. A rapid correct diagnosis by anamnesis, clinical signs, endoscopical aspect and demonstration of toxin in the stool allows an efficient treatment. The therapeutic modalities, especially in recurrency, are delineated. In addition, the unusual and etiologically still unknown illness of penicillin induced segmental hemorrhagic colitis will be discussed as well. PMID- 1926013 TI - [Thrombolysis in acute myocardial infarct]. AB - The introduction of intravenous, high-dose thrombolytic therapy during a brief period has markedly reduced mortality of patients with acute myocardial infarction. While mortality can be reduced by any of the available thrombolytic agents that are applied within the first 24 hours following onset of chest pain, the effects on preservation of cardiac performance which can be achieved following application of thrombolytic therapy within four hours do markedly differ as a consequence of pharmacological properties and rate of early perfusion and patency between different agents. To preserve cardiac performance, rt-PA is the primary candidate to achieve early reperfusion and APSAC the one to prevent reocclusion. In contrast to these, the fibrin-unspecific thrombolytic agent, streptokinase, with its long fibrinolytic activity, seems to be the primary choice to achieve recanalization of vessels occluded by mixed and organized thrombus consisting of platelets and erythrocytes. Of particular importance is, that reocclusion has been prevented by administering an adjuvant therapy of aspirin and heparin. A number of questions are currently being studied and cannot be answered at this date: a) the majority of data does not support the use of a thrombolytic therapy in patients with unstable angina, b) there is no substantial benefit demonstrated in administering thrombolytic therapy prior to transportation of the patient to the hospital, c) the precise dosage of thrombolytic agents and of possible combinations, d) the putative impact of future antiplatelet drugs to further improve late patency. PMID- 1926014 TI - [The treatment of heart insufficiency in coronary heart disease]. AB - In acute as well as in chronic ischemic heart disease, congestive heart failure indicates a poor prognosis. Treatment after acute myocardial infarction should differentiate between specific subsets. In cardiogenic shock due to extensive ischemic damage, acute revascularization by PTCA or CABG improves the otherwise poor outcome substantially. In congestive heart failure, pre- and afterload reduction by nitrates should be combined with dopamine if systolic blood pressure is below 100 mmHG or dobutamine if an inotropic substance is necessary despite systolic blood pressure greater than 100 mmHg. Amrinone is a potent alternative which combines positive inotropic and vasodilating properties. In chronic ischemic heart disease, congestive heart failure is a clearly defined indication for complete revascularization, if possible. As to drug treatment, progression of the disease characterized by a cardiomyopathy of overload as well as neurohormonal and peripheral maladaptation should be stopped in parallel with symptom relief. Therefore, ACE-Inhibitors are combined very early with diuretic treatment, and digitalis should be added in refractory patients. PMID- 1926015 TI - [Psychosocial risk factors and coronary heart disease]. AB - A literature review shows that besides the classical risk factors smoking, hypercholesterolemia, hypertension and age psychosocial risk factors have been identified in the development and progress of coronary heart disease. They can be divided into four categories: inadvertent socio-economic conditions, insufficient physical exercise, type-A personality and emotional problems and lack of social support. PMID- 1926016 TI - [Diagnostic procedures in patients with known coronary heart disease]. AB - Patients with coronary artery disease can be stratified by noninvasive techniques into risk-groups for further diagnostic and therapeutic management. The prognostic impact of the patient's history, physical examination and ECG are discussed. With this clinical assessment a high-risk group of patients, who should undergo coronary angiography, can be identified. In a low-risk group, further evaluation depends on results of exercise-stress testing. The relative value of exercise ECG, thallium-201-scintigraphy and radionuclide ventriculography in this special clinical setting are discussed in detail. PMID- 1926017 TI - [Percutaneous transluminal coronary angioplasty]. AB - Since its first application in a patient, PTCA has undergone a tremendous evolution: Based on growing experience and due to technical developments, indications have been markedly extended. Despite the fact that PTCA has been used in more risky situations, the primary success rate has risen and the rate of severe complications has dropped. This evolution is shown based on the Basel experience and on data from Switzerland. The problem of restenosis, however, has not been solved and remains the main problem to be looked for during follow-up of these patients. PMID- 1926018 TI - [Surgical treatment of coronary heart disease]. AB - The goal of coronary surgery in stable angina pectoris is relief of symptoms and improvement of prognosis, whereas in unstable angina pectoris the main purpose is the prevention of infarction. In 'mechanical' complications of infarction, surgery is undertaken to treat severe congestive heart failure or cardiogenic shock. Prophylactic operations in asymptomatic patients are generally recommended in three-vessel disease, left main-stem stenosis and critical stenosis of the left anterior descending artery with the purpose to reduce the risk of myocardial infarction and to improve survival. Early surgically mortality was about 1% some years ago, but is actually slightly higher, mainly due to selection of high-risk patients since the introduction of PTCA. Late mortality is about 5% after one year and about 25% after ten years. The early patency rate of vein grafts is more than 90% and decreases about 5% per year, whereas results with arterial grafts are even better. Early surgical mortality in patients with mechanical complications is very high (40 to 50%) in the acute stage of infarction; results in the chronic stage are much better (5 to 10%). PMID- 1926019 TI - [Intramural rehabilitation following infarction]. AB - Major objectives of a comprehensive cardiac rehabilitation include not only an increased functional capacity by physical training with aerobic exercise as a cornerstone, a reduction in morbidity and mortality by secondary preventive measures and a rapid return to work, but also an improvement in subsequent quality of life. Different forms of rehabilitation programs may be equally successful: a four-week institutional rehabilitation course or an outpatient rehabilitation program with 2 to 3 weekly training sessions for 3 to 6 months. If the guidelines for graduated activity are respected, the training bears a low risk. Patients with low exercise capacity for cardiac, vascular or other reasons, as those otherwise handicapped, should not join a formal rehabilitation program, but should be followed on an individual basis. In those patients as well as in many others the home physician plays a crucial role in the long-time supervision and counseling. PMID- 1926021 TI - Surveillance of work related and occupational respiratory disease--SWORD. PMID- 1926020 TI - BOOP and COP. AB - BOOP and COP are essentially the same condition and represent one of many ways in which the lung may respond to an inflammatory stimulus. Some underlying causes of BOOP have been identified but in many cases no cause can be found. The clinical and radiological features are of a pneumonic illness that responds to corticosteroids rather than antibiotics, but as milder cases are being identified the clinical spectrum is widening. Most cases can be confidently diagnosed only by open lung biopsy, but bacteriological lavage and transbronchial biopsy followed by a trial of steroids may sometimes be considered. PMID- 1926022 TI - Comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children. AB - The prevalence of reversible airways obstruction has been assessed in children in three areas in Zimbabwe--northern Harare (high socioeconomic class urban children), southern Harare (low socio-economic class urban children), and Wedza Communal Land (rural children from peasant families). Peak expiratory flow (PEF) was measured before and after six minutes' free running in 2055 Zimbabwean primary school children aged 7-9 years. Height and weight were measured and nutritional state expressed as a percentage of the 50th centile for age (Tanner Whitehouse standards). Reversible airways obstruction was deemed to be present when peak expiratory flow was below the 2.5th centile for height before exercise and rose by more than 15% after inhalation of salbutamol and when it fell by 15% or more after exercise and rose again after salbutamol. The prevalence of reversible airways obstruction was 5.8% (95% confidence interval 4.1-7.5%) in northern Harare (n = 726); 3.1% (1.8-4.5%) in southern Harare (n = 642), and 0.1% (0.0-0.4%) in Wedza (n = 687). In northern Harare, the only study area in which white children were found, the prevalence of reversible airways obstruction was similar in white (5.3%, 10/188) and black (5.9%, 32/538) children. Indicators of nutritional state also showed no significant differences between white and black children in northern Harare but were lower in southern Harare and lower still in Wedza. Urban living and higher material standards of living appear to be associated with a higher prevalence of reversible airways obstruction in children in Zimbabwe. PMID- 1926023 TI - Clinical spectrum of cryptogenic organising pneumonitis. AB - Cryptogenic organising pneumonitis (bronchiolitis obliterans organising pneumonia) is an uncommon condition that often responds to steroids. It is characterised clinically by constitutional symptoms, pathologically by intra alveolar organising fibrosis, and radiologically by patchy pulmonary infiltrates. Its full clinical spectrum and course are only partially described and understood. Six patients are described, seen over three years, with considerably diverse clinical and radiological presentations (two had diffuse lung infiltrates, two had peripheral lung infiltrates, and two had localised lobar involvement) and with very varying severity of disease (two with a life threatening illness, three with appreciable subacute constitutional symptoms, and one with mild symptoms). It is concluded that cryptogenic organising pneumonitis can present in various ways. A set of diagnostic criteria are proposed which will help in the recognition of this syndrome, which is probably underdiagnosed. PMID- 1926024 TI - Randomised controlled trial of the effectiveness of a respiratory health worker in reducing impairment, disability, and handicap due to chronic airflow limitation. AB - A randomised controlled trial was undertaken to determine whether a respiratory health worker was effective in reducing the respiratory impairment, disability, and handicap experienced by patients with chronic airflow limitation attending a respiratory outpatient department. The 152 adults (aged 30-75 years) who participated had a prebronchodilator forced expiratory volume in one second (FEV1) below 60% predicted and no other disease. They were randomised to receive the care of a respiratory health worker or the normal services provided by the outpatient department. The respiratory health worker provided health education and symptom and treatment monitoring in liaison with primary care services. After one year there was little difference between the two groups in spirometric values (FEV1 and forced vital capacity before and after salbutamol 200 micrograms), disability (six minute walking distance and paced step test), and handicap (sickness impact profile, hospital anxiety and depression scale). Patients not looked after by the respiratory health worker were more likely to die (relative risk 2.9 (95% confidence limits 0.8, 10.2); when age and FEV1 were controlled for this risk increased to 5.5 (95% confidence limits 1.2, 24.5). Patients looked after by the respiratory health worker attended their general practitioner more frequently and were prescribed a greater range of drugs. This is the third study to have found limited measurable benefit in terms of morbidity from the intervention of a respiratory health worker. This may be due to the ability of such workers to keep frail patients alive. PMID- 1926025 TI - Morbidity in nocturnal asthma: sleep quality and daytime cognitive performance. AB - Most patients with asthma waken with nocturnal asthma from time to time. To assess morbidity in patients with nocturnal asthma nocturnal sleep quality, daytime sleepiness, and daytime cognitive performance were measured prospectively in 12 patients with nocturnal asthma (median age 43 years) and 12 age and intellect matched normal subjects. The median (range) percentage overnight fall in peak expiratory flow rate (PEF) was 22 (15 to 50) in the patients with nocturnal asthma and 4 (-4 to 7) in the normal subjects. The patients with asthma had poorer average scores for subjective sleep quality than the normal subjects (median paired difference 1.1 (95% confidence limits 0.1, 2.3)). Objective overnight sleep quality was also worse in the asthmatic patients, who spent more time awake at night (median difference 51 (95% CL 8.1, 74) minutes), had a longer sleep onset latency (12 (10, 30) minutes), and tended to have less stage 4 (deep) sleep (-33 (-58, 4) minutes). Daytime cognitive performance was worse in the patients with nocturnal asthma, who took a longer time to complete the trail making tests (median difference 62 (22, 75) seconds) and achieved a lower score on the paced serial addition tests (-10 (-24, -3)). Mean daytime sleep latency did not differ significantly between the two groups (2 (-3, 7) minutes). It is concluded that hospital outpatients with stable nocturnal asthma have impaired sleep quality and daytime cognitive performance even when having their usual maintenance asthma treatment. PMID- 1926026 TI - Hospital admission rates and the prevalence of asthma symptoms in 20 local authority districts. AB - Representative samples of 20-44 year old men living in 20 local authority districts in England were surveyed in 1986 by postal questionnaire and asked about symptoms associated with asthma and treatment for asthma. Regional health authorities provided information on all hospital discharges of men of the same age living in the same districts. Specific information was also provided on discharges where the primary cause of admission was for asthma. Admission rates for asthma were related to the prevalence of night time breathlessness and independently to the all cause admission rate for men of the same age. Admission rates were not significantly related to prescription rates of either corticosteroids or beta 2 agonists for symptomatic men. This lack of association is hard to interpret without further information on variation in the severity of disease. These data show that admission rates for asthma are not dictated solely by health service characteristics, such as availability of beds or the "style" of the physician, but also reflect need. More research is required on how best to reduce the local prevalence and severity of asthma. PMID- 1926027 TI - Creatine kinase activity in patients with brittle asthma treated with long term subcutaneous terbutaline. AB - Infused beta 2 agonists have been shown to cause focal myocardial necrosis. Serum creatine kinase activity was compared in 13 patients with brittle asthma currently being treated with subcutaneous terbutaline and an age and sex matched control group of patients with moderate asthma having inhaled treatment only. The median serum total creatine kinase activity for patients receiving subcutaneous terbutaline (211 units/l) was greater than that for the control group (120 units/l). The cardiac specific isoenzyme component of creatine kinase was not raised in either group, and the electrocardiograms and serum aspartate aminotransferase activity were normal. Electromyograms in five patients receiving subcutaneous terbutaline with high creatine kinase activity showed changes consistent with myositis in two, one of whom was subsequently shown to have a metabolic myopathy, which is thought to be long standing. No pathological changes were seen in the myocardium at necropsy in a patient who died from an acute attack of asthma while taking subcutaneous terbutaline. These results suggest that the raised creatine kinase activity seen in patients receiving this treatment is unlikely to be myocardial in origin. PMID- 1926028 TI - Pneumothorax and malignant mesothelioma in patients over the age of 40. AB - Five patients over the age of 40 with malignant mesothelioma of the pleura presented with a spontaneous pneumothorax in the course of five years. The diagnosis of malignant mesothelioma was not suspected at surgery but was made by histological examination of the pleurectomy specimens. During this time 91 pleurectomies for recurrent pneumothorax were performed, 45 in patients over the age of 40; malignant mesothelioma therefore accounted for 11% of spontaneous pneumothorax requiring pleurectomy in this age group. The association of spontaneous pneumothorax and malignant mesothelioma is not emphasised in current publications. These five cases highlight the need for all pleurectomy specimens in cases of spontaneous pneumothorax to be sent for histological examination and for a full occupational history to be taken, especially in older patients. PMID- 1926029 TI - Value of nocturnal oxygen saturation as a screening test for sleep apnoea. AB - The sensitivity and specificity of overnight recording of arterial oxygen saturation (SaO2) in routine clinical practice was evaluated in 41 subjects who were being investigated for possible sleep apnoea-hypopnoea syndrome. SaO2 was measured with an ear probe oximeter (Biox IIa) and chart recorder during an "acclimatisation" night immediately before a detailed polysomnographic study. The recordings were classified by two observers as positive, negative, or uninterpretable. Twelve of the 41 patients had the obstructive sleep apnoea syndrome when defined in terms of an apnoea-hypopnoea index greater than 15 events an hour on the second night. The sensitivity of nocturnal SaO2 on the acclimatisation night when the diagnostic criterion was an apnoea-hypopnoea index of greater than 5, greater than 15, and greater than 25/h was 60%, 75%, and 100% respectively. Corresponding values for specificity were 95%, 86%, and 80%. Oximetry alone therefore allowed recognition of a moderate or severe sleep apnoea syndrome. In routine practice an appreciable number of equivocal results is likely and repeat oximetry or more detailed polysomnography will then be required if clinical suspicion is high. PMID- 1926030 TI - Accuracy of diagnostic coding of hospital admissions for cryptogenic fibrosing alveolitis. AB - To determine the accuracy of diagnostic coding of cryptogenic fibrosing alveolitis, the case notes of 166 admissions to four hospitals were reviewed. These consisted of all admissions that had been coded as "idiopathic fibrosing alveolitis" (ICD code 516.3: 97 admissions) or as "postinflammatory pulmonary fibrosis" (ICD code 515.9: 69 admissions). Of 88 available records of admissions coded as idiopathic fibrosing alveolitis, 70 (80%) patients had definite cryptogenic fibrosing alveolitis, and six (7%) possible cryptogenic fibrosing alveolitis according to predetermined conventional clinical criteria. Only seven (8%) admissions were clearly coded wrongly. Sixty four records were available for patients coded as having postinflammatory pulmonary fibrosis; 16 (25%) of these patients had definite cryptogenic fibrosing alveolitis, a further 12 (19%) had possible cryptogenic fibrosing alveolitis or fibrosing alveolitis with a connective tissue disorder, and the remainder had a very wide range of diagnoses. In this study the idiopathic fibrosing alveolitis (ICD 516.3) code was relatively reliable, but a substantial proportion of admissions coded under postinflammatory pulmonary fibrosis (ICD 515.9) also had cryptogenic fibrosing alveolitis and code 515.9 was of little diagnostic value. The data are inadequate for case finding, though in respect of cryptogenic fibrosing alveolitis may be adequate for planning purposes. There continues to be a need for more medical input into the process of diagnostic coding. PMID- 1926031 TI - Cyclosporin as a treatment for interstitial lung disease of unknown aetiology. AB - Ten patients with progressive, symptomatic interstitial lung disease of unknown aetiology who were treated with cyclosporin A were reviewed. Five had clinical and histopathological features of cryptogenic fibrosing alveolitis and five a progressive restrictive lung disease characterised by interstitial infiltration with lymphocytes and minimal fibrosis, which could not be classified precisely. Three patients with lymphocytic infiltration showed a response to initial treatment with cyclosporin A alone at high dosage, but toxicity precluded further treatment. All 10 patients then received low doses of cyclosporin A and prednisone. Three of the patients with cryptogenic fibrosing alveolitis and all five patients with lymphocytic infiltration responded with a reduction in dyspnoea or an increase in vital capacity, or both; cyclosporin A appeared to be effective, or at least to have a corticosteroid potentiating effect. A high incidence of side effects occurred, though these do not necessarily prohibit the long term use of cyclosporin A when it is indicated clinically. Cyclosporin A may be effective in the treatment of interstitial lung disease of unknown aetiology. Further studies are required to determine the long term outcome of treatment. PMID- 1926033 TI - Albendazole in the treatment of pulmonary echinococcosis. AB - Ten patients with pulmonary hydatid disease diagnosed on the basis of a chest radiograph and a positive response to the indirect haemagglutination test for hydatid disease were treated with albendazole 10 mg/kg/day for eight weeks. None of the 10 patients showed any radiological or serological improvement with this treatment regimen. Albendazole in these doses appears to have little role in the treatment of pulmonary hydatid disease. PMID- 1926032 TI - Pleural abrasion: a new method of pleurodesis. AB - Sixty patients (48 male, 12 female; median age 32 (range 16-72) years) underwent pleural abrasion for persistent or recurrent pneumothorax. Fifty patients had recurrent pneumothorax and 10 persistence of a first pneumothorax despite conservative treatment; two had bilateral pneumothoraces. Pleural abrasion was carried out with a domestic nylon scouring pad and blebs or bullae were ligated or stapled and excised. Intercostal drainage was discontinued after a median time of two days, median serosanguinous loss was 250 ml, and the median postoperative stay in hospital was four days. During the median follow up period of 32 (range 19-52) months pneumothorax has recurred in one patient. PMID- 1926034 TI - Needle aspiration techniques in the diagnosis of pneumonia. PMID- 1926035 TI - Ovine psittacosis and sarcoidosis in a pregnant woman. AB - A woman in the first trimester of pregnancy presented with pneumonia and hilar lymphadenopathy after exposure to lambing ewes. She subsequently aborted. Infection with Chlamydia psittaci of ovine origin was confirmed. Pregnant women are susceptible to this infection, which may cause life threatening disease. The patient also had features of sarcoidosis, and the two conditions ran a similar time course. There is a possibility that ovine psittacosis caused an illness indistinguishable from sarcoidosis. PMID- 1926036 TI - Pneumomediastinum after a transbronchial biopsy. AB - A pneumomediastinum occurred after a transbronchial biopsy in a woman with pulmonary fibrosis and was confirmed by computed tomography. Although pneumomediastinum has a pathogenesis similar to that of pneumothorax it has not been reported after transbronchial biopsy. PMID- 1926037 TI - Pulmonary dirofilariasis causing a solitary lung mass and pleural effusion. AB - A 63 year old patient presented with a pleural effusion and a solitary lung lesion on the computed tomogram. He was found to have an inflammatory granuloma due to Dirofilaria immitis at thoracotomy. PMID- 1926038 TI - Fatal haemoptysis from the pulmonary artery as a late complication of pulmonary irradiation. PMID- 1926039 TI - Role of thrombin in arterial thrombosis: implications for therapy. PMID- 1926040 TI - Platelet GPIIb-IIIa: molecular variations and alloantigens. AB - Recent advances in molecular and cellular biology have made it possible to build upon previous serologic and biochemical studies of glycoproteins IIb and IIIa in important and exciting ways. In addition to providing a detailed basic understanding of the polymorphisms that are responsible for Glanzmann's thrombasthenia, and in other cases for eliciting an alloimmune response, the molecular characterization of platelet membrane glycoprotein polymorphisms is expected to have an increasingly large clinical impact. As the molecular basis of the remaining platelet antigen systems becomes known, our ability to design novel diagnostic and therapeutic approaches for the care and management of patients with PTP and NATP should improve. For Glanzmann's disease, the future holds the promise of gene therapy to correct the platelet abnormality. Establishment of animal models for GT will be an important first step in this direction. PMID- 1926041 TI - Status of gene transfer for hemophilia A and B. PMID- 1926042 TI - Deep vein thrombosis: new non-invasive diagnostic tests. PMID- 1926043 TI - A continuous flow reactor system for the study of blood coagulation. PMID- 1926044 TI - Hirudin and derivatives as anticoagulant agents. PMID- 1926045 TI - Pathophysiology of vitamin K-deficiency and oral anticoagulants. PMID- 1926046 TI - The structures of domains of blood proteins. PMID- 1926047 TI - Progress in the clinical management of haemophilia. PMID- 1926048 TI - Platelet transfusions a constantly evolving therapy. PMID- 1926049 TI - Genetic basis of hemophilia A. PMID- 1926050 TI - The complexity of platelet adhesion to extracellular matrices. PMID- 1926051 TI - Heparin or heparan sulfate--what is the difference? PMID- 1926052 TI - The extrinsic pathway inhibitor: a regulator of tissue factor-dependent blood coagulation. PMID- 1926053 TI - Prevention and management of recurrent disease after arterial reconstruction: new prospects for pharmacological control. PMID- 1926054 TI - Strategies for the improvement of thrombolytic agents. PMID- 1926055 TI - Extrinsic pathway inhibitor (EPI) released to the blood by heparin is a more powerful coagulation inhibitor than is recombinant EPI. AB - EPI released to the blood after injection of heparin, as well as recombinant EPI (r-EPI) added to normal plasma prolonged both the dilute Tissue Thromboplastin (TTP) time and the Activated Partial Thromboplastin Time (APTT). It is known that EPI inhibits both factor Xa and the factor VIIa-TTP complex. The prolongation of the APTT by EPI reflects only its inhibition of factor Xa. Addition of anti-EPI immunoglobulins (IgG) to normal plasma shortened the dilute TTP time 7.3 seconds (p less than 0.001) and the APTT by 0.7 seconds (p less than 0.001). In postheparin plasma, with polybrene added to neutralize the direct effect of heparin, the TTP was about 26 seconds longer and the APTT about 9 seconds longer than baseline values. These effects were completely abolished by anti-EPI IgG, as were the effects of r-EPI. The EPI activity (chromogenic substrate-assay) of this postheparin plasma was 1.7 U/ml. The EPI activity of the plasma spiked with r-EPI to obtain comparable effects on clotting were much higher; about 22 U/ml for the TTP effect and about 5 U/ml for the APTT effect. The findings indicate that r-EPI is considerably less potent than postheparin EPI as inhibitor of plasma coagulation. This is most striking when coagulation is initiated through the extrinsic pathway. Possibly, the anticoagulant effect of r-EPI mainly depends on its Xa inhibitory effect. PMID- 1926056 TI - The influence of time, temperature and packed cell on activated partial thromboplastin time and prothrombin time. AB - Activated partial thromboplastin time (APTT) and prothrombin time (PT) were performed in four groups of studies in order to evaluate the influences of time, temperature, and different forms of plasma storage to the result. Different designs for storage of the plasmas were studied, including the plasmas stored either with or without packed cells, the plasmas stored in the cuvette with exact volume for performing the test or in the test tube. The temperatures for store of the plasma were at room temperature, at 4 degrees C and at -70 degrees C. The time for store of the plasma was from 1 hour up to 7 hours. The plasmas included normal pooled plasmas and diseased plasmas. From this study, it is found that the PT test was not easily affected by the temperature, storage time and the form of storage in comparison with the APTT test which was much easily affected by the above conditions. APTT should be done within 2 hours after sampling and the plasma should be stored with the packed cells at 4 degrees C in order to obtain a reliable result. PT could be done within 7 hours without influence to the result if the plasma was stored with the packed cells at 4 degrees C. No significant cold-induced shortening of PT could be noted when the plasma was incubated at 4 degrees C up to 7 hours. In either PT or APTT, the most suitable condition for storing the plasma should be with the packed cells at 4 degrees C. PMID- 1926057 TI - Choline inhibition of prothrombin activation. AB - A computer-interfaced spectrophotometric kinetic assay for prothrombin activation was developed, coupling the production of thrombin to a thrombin-specific amidolytic chromogenic reaction. As thrombin accumulated initially at constant velocity, the simultaneous release from S-2238 of pNA conformed to an acceleration function. Adherence to the acceleration function of the temporally increasing A400 of pNA was evaluated after transforming the data into linear format which permitted linear regression analysis. High correlation coefficients, routinely greater than 0.99, verified linearity of thrombin production in individual assay mixtures. As prothrombin concentrations were varied, factor Xa exhibited Michaelis-Menten kinetics. Added choline produced a pattern of mixed type inhibition. Replots of LB slopes and intercepts versus choline concentration gave apparent Ki and Ki' values (mM): 22 +/- 3 and 48 +/- 7 without factor Va, 25 +/- 4 and 41 +/- 4 with factor Va. PMID- 1926058 TI - Age, cardiovascular risk factors and coronary heart disease as determinants of platelet function in men. A multivariate approach. AB - Older age, the cardiovascular risk factors and arteriosclerosis have been reported to be associated with stimulated platelet function. To evaluate the relative importance of these factors in determining platelet function, a cross sectional multivariate study in 191 men, 113 healthy subjects and 78 patients with angiographically documented coronary heart disease, was performed. In healthy subjects, stepwise multiple linear regression identified age to be a major determinant of platelet aggregability. After induction with both ADP and collagen the platelet aggregatory response markedly increased with age. In the patients, platelet function was not age dependent. In multivariate analysis of variance, neither smoking status nor hypercholesterolemia (greater than or equal to 240 mg/dl) were determinants of platelet function in either group. An increase in systolic blood pressure was associated with slightly more inhibited ADP induced aggregation in both healthy subjects and patients with coronary heart disease. In patients compared to healthy subjects, aggregation after induction with ADP and collagen was markedly enhanced and the in vitro formation of thromboxane after collagen stimulation increased. Thus, by multivariate analysis, age and the presence or absence of coronary heart disease were found to be major determinants of platelet function. In contrast, the cardiovascular risk factors smoking, hypercholesterolemia and hypertension were associated with only minor or no alterations of platelet function. PMID- 1926059 TI - Effects of subcutaneously administered dermatan sulfate (MF 701) on the coagulation and fibrinolytic parameters of healthy volunteers. AB - Eight healthy volunteers were given single subcutaneous doses of dermatan sulfate (DS, 100, 200 and 400 mg), heparin (5,000 IU) and placebo in random order. Wash out between treatments was greater than or equal to 10 days. Serial blood samples were taken before and up to 24 hours after treatment to measure coagulation and fibrinolytic parameters. Thrombin generation was significantly inhibited by DS and heparin as compared to placebo. The effect of DS was dose-dependent. Peak inhibition after 200 mg DS was comparable to that of 5,000 IU heparin, but lasted longer. A small, bordeline significant prolongation of APTT was observed after 400 mg DS and heparin. The changes in PAI and fibrinolytic activities were those of the circadian variation. No changes were seen in the other parameters tested. In conclusion, single s.c. doses of DS (200, or 400 mg) inhibit ex vivo thrombin generation equally or more than 5,000 IU heparin and for a longer time. The effect of both treatments on fibrinolysis is negligible. PMID- 1926060 TI - Prothrombin Himi; an abnormal prothrombin characterized by a defective thrombin activity. AB - An abnormal prothrombin has been detected in a 26-year-old female, who had no history of excessive bleeding. Prothrombin activity was approximately 10% when measured using either the classical one-stage assay or the assay with Echis carinatus venom, whereas prothrombin antigen level was normal. In keeping with current nomenclature practices, the abnormal prothrombin was designated "Prothrombin Himi". The electrophoretic behavior and calcium binding properties of Prothrombin Himi did not differ significantly from normal. Prothrombin Himi was isolated by chromatography on Q-Sepharose. Electrophoretic migration of the purified abnormal prothrombin on SDS-PAGE was normal. Upon prothrombin activation by Echis carinatus venom, the clotting activity produced from Prothrombin Himi was only 37% of the normal level after 90 minutes of the activation time, where as the amidolytic activity was almost the same as normal. The cleavage patterns of Prothrombin Himi by factor Xa or Echis carinatus venom investigated by SDS PAGE, were found to be normal. These results indicate that Prothrombin Himi was characterized by a defective thrombin enzymatic activity. PMID- 1926061 TI - Antithrombin III modulates the effect of thrombin on the metabolism of glycosaminoglycans in cultured endothelial cells. AB - We previously reported that a treatment of cultures of endothelial cells from bovine aorta with thrombin resulted in a less accumulation of glycosaminoglycans (GAG) in the cell layer. In the present study, we found that thrombin-induced decrease in the accumulation of [35S]sulfate-labeled GAG (35S-GAG) such as heparan sulfate was prevented by antithrombin III (AT III) but not by heparin cofactor II (HC II). However, AT III did not show a significant effect on the 35S GAG accumulation individually. Pretreatment of the cell layer with neither AT III nor HC II showed any preventive effect. When GAG in the cell layer was labeled with both [35S]sulfate and [3H]glucosamine, neither thrombin nor a combination of thrombin with AT III changed the ratio of the radioactivity of 35S to that of 3H. Although thrombin stimulated the release of 35S-GAG from the cell layer, AT III completely prevented the stimulatory effect. In conclusion, it was suggested that AT III may inhibit the thrombin action on GAG metabolism of endothelial cells to prevent thrombosis in vivo. PMID- 1926062 TI - In vitro effects of picotamide on human platelet aggregation, the release reaction and thromboxane B2 production. AB - We studied the in vitro effects of picotamide (N,N' bis 3 picolyl-4-methoxy isophthalamide) on human platelet aggregation, the release reaction and the production of thromboxane B2 (TxB2) induced by several platelet agonists. The effects of picotamide were compared to those of acetylsalicylic acid (ASA). Picotamide (0.5 mmol/l) inhibited platelet aggregation, the release of ATP and TxB2 production induced by ADP, arachidonic acid (AA), collagen or the prostaglandin endoperoxide (PE) analogue U46619. ASA (0.5 mmol/l) did not affect platelet aggregation and the release of ATP induced by U46619. Picotamide and ASA inhibited the AA-induced platelet TxB2 production both under stirring and non stirring conditions, whereas the pure thromboxane A2 receptor antagonist BM13177 (0.5 mmol/l) was inhibitory only under stirring conditions. Since under non stirring conditions platelet aggregation does not occur, picotamide directly inhibits TxB2 production, whereas BM13177 inhibits the potentiation of TxB2 production due to TxA2/PE-dependent platelet aggregation. Malondialdehyde (MDA) production by unstirred platelets stimulated with AA was not significantly inhibited by picotamide. In conclusion, picotamide inhibits the TxA2/PE-dependent platelet responses to agonists by a double mechanism: (i), TxA2/PE antagonism; (ii) inhibition of thromboxane synthase. PMID- 1926063 TI - A novel principle for assessment of stimulated fibrinolysis. AB - After venous occlusion (VO), D-dimer levels were measured by means of an ELISA technique, in citrated plasma clotted by thrombin and in serum from whole blood. D-dimer levels increased with duration of incubation (30 min to 24 hours). D dimer values, both in clotted plasma and in serum (n = 12), incubated 4 hours at room temperature, correlated well with euglobulin clot lysis time (ECLT) (r = 0.85 and -0.89, respectively, p less than 0.002) and tissue plasminogen activator (t-PA) activity, (r = 0.82 and 0.83, respectively, p less than 0.002). D-dimer concentrations from plasma and serum (n = 25) were compared (r = 0.90, p less than 0.001). Healthy volunteers (n = 65) were tested to establish reference values in serum from post-occlusive whole blood samples incubated 4 hours prior to centrifugation. Finally, a patient group (n = 62) was examined. For the whole material (n = 152) such D-dimer concentrations correlated well with both ECLT (r = -0.85, p less than 0.001) and t-PA activity (r = 0.81, p less than 0.001). D dimer levels in serum were determined by a latex agglutination test as well. These semi-quantitative values also correlated significantly with both ECLT (r = 0.86, p less than 0.001) and t-PA activity (r = 0.87, p less than 0.001). We conclude that measurement of D-dimer as described above, represents a simple and accurate method for assessment of global fibrinolytic activity following VO. The latex agglutination test is particularly suitable as a screening procedure. PMID- 1926064 TI - Combined aspirin and sulfinpyrazone in the prevention of recurrent hemodialysis vascular access thrombosis. AB - We carried out a pilot study in 15 hemodialysis patients with recurrent vascular access thrombosis to examine whether the combination of low dose aspirin (85 mg once daily) and sulfinpyrazone (200 mg three times daily) is safe and effective in the prevention of vascular access thrombosis. Hemostatic measurements were performed prior to and after four weeks of starting the drug combination. Baseline values for fibrinopeptide A were elevated in all patients while those for platelet factor 4, fibrinogen, antithrombin III and protein C were generally within normal limits. A major reduction in the frequency of vascular access thrombosis from 0.114 per month to 0.04 per month was noted during combined drug treatment (p less than 0.001). Although in vitro platelet aggregation to various stimuli was markedly suppressed and platelet thromboxane B2 formation was almost completely inhibited in patients on aspirin/sulfinpyrazone, this was not associated with a significant further prolongation of the bleeding time. A relatively high rate of complications, particularly mild gastrointestinal bleeding, was noted in patients on aspirin/sulfinpyrazone that could not be predicted on the basis of pre-treatment hemostatic test results. PMID- 1926065 TI - Cloning and partial sequence of a cDNA for rabbit prothrombin. AB - A 1466 base pair cDNA for rabbit prothrombin has been isolated and partially sequenced. The deduced amino acid sequence shows considerable homology with the sequences of human and bovine prothrombin. The cDNA extends from the equivalent of nucleotide 516 in the bovine sequence through the coding region and 99 nucleotides in the 3' non-coding region. PMID- 1926066 TI - Antithrombin activity of a fucan sulfate from the brown seaweed Ecklonia kurome. AB - The mechanism of antithrombin action of a fucan sulfate (C-II), which was isolated from the brown seaweed Ecklonia kurome, was examined by clotting method using a thrombin-fibrinogen system and by amidolytic method using a chromogenic substrate in the presence and the absence of antithrombin III (AT III) or heparin cofactor II (HC II). C-II significantly inhibited the clotting of fibrinogen by thrombin even in the absence of the protease inhibitors, and the amidolytic activity of the protein only in the presence of HC II. C-II was not adsorbed on an AT III-agarose column and its anticoagulant activity in AT III-depleted plasma was the same as that in normal one. Examination of interaction of C-II with fibrinogen by gel filtration chromatography demonstrated that C-II bound to the protein. These results indicated that the antithrombin activity of C-II was mediated by HC II and not by AT III, and that the polysaccharide bound to fibrinogen, thereby blocking thrombin action, and also that its direct thrombin inhibition was very weak. PMID- 1926067 TI - Comparative study of protein C activators from the Agkistrodon snake venoms. PMID- 1926068 TI - Intraduodenal absorption of the new UF-heparin salt ITF 1057 in the conscious dog. PMID- 1926069 TI - Platelet count, mean platelet volume, and platelet dimensional width in professional cyclists during races. PMID- 1926070 TI - [We and child protection]. PMID- 1926071 TI - [Explorative abrasion--obsolete?]. PMID- 1926072 TI - [Are you always there? About accidents we can avoid]. PMID- 1926073 TI - [Accidents in nursing homes]. AB - 169 "injury situations" involving 61 patients were registered in a nursing home during one year. Four patients were sent to hospital. A few patients had several falls. Men were more prone to injury than women. Age itself seemed to be of no importance. Patients on shortterm admittance were at high risk. In general patients with dementia were not at higher risk but suffered the more serious injuries and were also involved in various episodes of patient violence. The risk of injuries is generally high in nursing homes. A certain risk must be accepted, but it is important to introduce prophylactic measures. A larger nursing staff might have prevented some of the situations. PMID- 1926074 TI - [Accident in Vaga in 1988]. AB - All accidents treated by the Primary Health Services in Vaga Municipality in 1988, were registered. There were altogether 498 accidents (124 accidents per 1,000 inhabitants per year). 418 injured persons were treated by the local health service, 80 were referred to hospital. The major mechanism of injury was falling (38%). The accidents occurred most frequently at home (38%), at the sports ground/outdoors (23%) or at work (17%). 11 injuries were very serious, none were lethal. 44 occurred during skiing. Our work to prevent accidents will give priority to: the mother and child clinic; environmental health; skiing accidents. PMID- 1926075 TI - [Examination of uterine hemorrhagic disorders using fractionated abrasion]. AB - The aim of the study was to describe the use of uterine curettage in the diagnosis of vaginal bleeding disorders. 301 pathological specimens were identified where uterine curettage was performed because of vaginal bleeding disorders. These specimens represented 23% of all recorded examinations in the files of Department of Pathology in 1987. Based on the above data the overall yearly rate of uterine curettage was estimated to be 8.7 per 1,000 women aged 20 years and over. The highest age-specific rate was found among women under 50 years of age. Most examinations (222), were carried out on tissue from women younger than 50. In only one of them (= 0.5%) was the diagnosis endometrial carcinoma. Most cases of carcinoma were found in women older than 50 years, with a total of seven out of 79 examinations. Questions should be raised about the routine use of uterine curettage, especially among women under 45 years of age. PMID- 1926076 TI - [Bone transplantation. Where are we in 1991?]. AB - Bone transplants are used in acute injuries, non-unions, defects after tumour, and total joint surgery. Autogenous cancellous bone from the iliac crest is still the most frequently used material. Allogeneic cadaver bone is an acceptable alternative for treating major defects after tumour resection, especially as osteoarticular graft about the knee. Allografts in total hip revisions have not been successful. Demineralized allogeneic bone matrix, bone morphogenetic protein and various bone mineral substitutes are experimental. There are distinct indications for pedicled and vascularized autografts which should be available whenever their use is warranted. PMID- 1926077 TI - [Diagnosis of Chlamydia trachomatis--culture or enzyme immunoassay? Norwegian multicenter study]. AB - Two EIA-tests (Chlamydiazyme, Abbott and Ideia, Celltech) were compared with culture for diagnosis of chlamydial infection in 1,185 patients from four different regions in Norway. The EIA-tests showed only minor differences in prevalences between the different regions (Chlamydiazyme: 4.1% to 5.4%; Ideia: 5.1% to 5.7%), but the agreement between the EIA-results was not satisfactory. 4.6 per cent of the specimens from Trondheim were culture-positive, but only 2.0% of the specimens from the other regions were culture-positive. Compared with the results from cultures from Trondheim (n = 349), the sensitivity, specificity, positive and negative predictive values for the EIA-tests were: Chlamydiazyme: 81.3%, 98.2%, 68.4% and 99.1% (81.3%, 96.4%, 52.0% and 99.1% without blocking test); Ideia: 93.8%, 98.5%, 75.0% and 99.7%. Culture should not be used as a routine method for detection of chlamydia in specimens sent by post without cooling. PMID- 1926079 TI - [Mammographic findings after breast-preserving procedure]. AB - Clinical evaluation of the breast after breast-conserving surgery and postoperative irradiation for carcinoma is made difficult by the changes induced by the treatment. Therefore mammographic evaluation, comprises an important part of the follow-up of these patients. The interpretation of the mammograms requires knowledge of the changes expected to occur after treatment. In this paper we describe such changes as experienced in our department. PMID- 1926078 TI - [Reduced ovarian function in infertile women. Experiences with the clomiphene test]. AB - The authors briefly describe the current understanding of follicular maturation, the influence of FSH on follicular maturation and the regulation of FSH secretion. They discuss the complex mechanisms of the impacts of clomiphene citrate, and how clomiphene citrate can be used in a test of ovarian reserve based on the FSH response. The article reports of the clomiphene citrate challenge test in patients referred to in vitro fertilization. PMID- 1926080 TI - [Resistance to chemotherapeutic agents in the treatment of cancer. Emphasizing the multiresistant phenotype]. AB - Despite considerable efforts, rather limited progress has been achieved in the treatment of disseminated cancer with chemotherapeutic agents during the last decade. Most tumours, especially those of epithelial origin, are more or less resistant to cytostatics right from initiation of therapy. Other tumours, on the other hand, like leukemias and lymphomas, are highly responsive initially but may become resistant during the course of therapy (secondary resistance). This type of resistance is due to random mutations in the malignant cells. Several mechanisms of cellular resistance have been described, the most important being characterized by simultaneous resistance to several unrelated chemotherapeutic agents (pleiotropic drug resistance or multidrug resistance). This mechanism is due to a membrane-associated efflux pump which transports the cytostatic agents out of the cells. The clinical importance of multidrug resistance and the possibility of inhibiting the function of the pump by pharmacological agents are currently being examined. PMID- 1926082 TI - [Screening for diabetic retinopathy]. AB - Photographic screening for diabetic retinopathy has been carried out for 40 months in an Eye Department. The results are described, with particular emphasis on cost-benefit. It is shown that the procedure finances itself with a wide margin. It probably provides better control of retinopathy than traditional clinical procedures. There may thus be a potential to reduce human suffering and the cost to society of visual impairment. The screening also provides the Department with better photographic services in general. PMID- 1926081 TI - [Dyspepsia in general practice]. AB - 110 patients who presented dyspeptic complaints to their general practitioner were interviewed using a questionnaire. Most patients had a long history of dyspeptic symptoms. 36 had been treated before for a peptic ulcer. Only 12 patients had a history of dyspepsia lasting less than three months. It is difficult to distinguish between organic and non-organic dyspepsia from the symptoms, and long-standing symptoms at any rate should be investigated further. The effect of medical treatment varies. Many patients have to live with their discomfort. PMID- 1926083 TI - [Cowden's disease. A syndrome with multiple hamartomas and neoplasias]. AB - We describe a patient with Cowden's disease, a rare genodermatosis characterized by multiple hamartomas and neoplasms of ectodermal, mesodermal and endodermal origin. The most characteristic findings are mucocutaneous lesions, including facial trichilemmomas, oral papillomatosis, and acral and palmoplantar keratoses. It is important to recognize these markers because of the high incidence of internal malignancy, the most common being breast cancer. Multiple extracutaneous hamartomas are described as being predominantly localized to breasts, thyroid gland, and gastrointestinal tract. Associated anomalies in multiple organs are frequently found. PMID- 1926084 TI - [Tumor lysis syndrome. A life-threatening complication during cytostatic treatment of chemosensitive types of cancer]. AB - Tumour lysis syndrome is characterized by hyperkalemia, hypermagnesemia, hyperphosphatemia, hyperuricemia and elevated levels of serum creatinine and urea, indicating renal dysfunction due to rapid lysis of a large number of tumour cells. Hypocalcemia is often found as well. Tumour lysis syndrome is most likely to occur after chemotherapy of cancers that are highly responsive to chemotherapeutic drugs, such as malignant lymphomas and acute leukemias, when there is a large burden of tumours. Another risk factor is impaired renal function before treatment. Tumour lysis syndrome is potentially life-threatening. During the first course of chemotherapy in particular, the patient should receive prophylactic treatment, and laboratory tests should be performed daily in order to avoid this serious complication. PMID- 1926085 TI - [Spinal puncture]. PMID- 1926086 TI - [Effect measures and confidence intervals]. AB - In order to exemplify the use of effect measures and confidence intervals in epidemiology, it is assumed that a group of patients treated with antiflogistic drugs were compared by repeated gastroscopy with a control group. The effect measures "incidence rate difference" and "incidence rate ratio" are used to compare ulcer incidence in the two groups of patients, and the corresponding confidence intervals are stated. On the other hand, if the registered parameter is prevalence rather than incidence rate, for instance the occurrence of prepyloric erosions at a certain time, the effect measures employed are "risk difference" and "risk ratio". An alternative to the latter is "odds ratio". PMID- 1926087 TI - [Late effects of nutritional deficiency during the first year of life]. AB - "Programming" may be defined as a process whereby a stimulus or an insult applied during a "critical" or "sensitive" period of development can result in a long term or permanent effect in the organism, with consequences for a number of metabolic, developmental and pathologic processes. The effect may sometimes occur after a long period of latency. Foetal life and infancy are such critical periods in man. Five examples of such programming are described from experiments in rats and baboons, after which the author discusses how nutritional deficiencies in foetal life and in infancy, either alone or combined with other adverse environmental factors, may have important consequences in later life. PMID- 1926089 TI - [Use of safety devices among children and adolescents]. AB - 5,000 Norwegian children from grades 5, 7 and 9 participated in a survey which questioned to what extent they use various kinds of safety equipment: safety belt, bicycle helmet, reflector, life-vest when in small boats, skateboard helmet and other skateboard safety devices. Use of all types of equipment decreases with increasing age. Except for reflectors, which are used most often by girls, there are no difference between girls and boys as regards use of safety equipment. The results indicate that there is a large potential for increasing the use of safety equipment among children. The consistent decrease in use of such equipment as children grow older shows the importance of understanding the social processes associated with use of safety equipment. PMID- 1926088 TI - [Self-reported accident frequency among children and adolescents]. AB - The article presents self-reported accidents among a representative group of Norwegian children from grades 5, 7 and 9. About half of the girls and 2/3 of the boys report having had at least one accident which had to be treated by a physician during their lifetime. This number is less than expected on the basis of accident-report figures, and may indicate that a small group of children have an unproportionally large number of accidents. About 35% of the children surveyed report having had an accident sometime during the past year. This is significantly more than expected and thus indicates report bias. There are important methodological difficulties associated with self-reporting of accidents among children. The difficulties can be minimized if the time period is limited and the types of accident are well-defined. If these conditions are fulfilled, self-reporting can be an important complement to accident-report figures. PMID- 1926090 TI - [Infant nutrition in Norway in the light of new research]. PMID- 1926091 TI - [Reflux esophagitis--a therapeutic problem]. PMID- 1926092 TI - [Ozone layer and life on Earth]. PMID- 1926093 TI - [Diving of patients with spinal cord injuries]. PMID- 1926094 TI - [Can mercury cause Alzheimer's disease?]. PMID- 1926095 TI - [A case of congenital porphyria in a calf]. AB - The case of a male calf affected with bovine congenital porphyria is reported in the present paper. The diagnosis was based on the specific and pathognomonic symptoms: lesions of the pale parts of the skin due to photosensitization, brownish discolouration of the teeth and urine, overall wasting and retardation of growth. The diagnosis was verified by analysis of the blood and urine: in the blood we found a high concentration of protoporphyrins (269 micrograms/l) and a rather low cell count (19 per cent), in the urine high concentrations of uro- and coproporphyrins (3340 and 2550 micrograms/l respectively) were determined. As there is no effective treatment for this disease, it was advised to keep the animal indoors and fatten it. The farmer did not follow this advice. The calf died within a few months. PMID- 1926096 TI - [Veterinary dentistry in dogs and cats; a survey among veterinarians]. AB - To gain an insight into the prevalence of dental disease in dogs and cats and forms of dental treatment, a postal survey was conducted among veterinarians in the Netherlands. Seventy per cent of the veterinarians replied that they made routine oral examinations of dogs and cats. Of dental diseases observed in dogs and cats periodontal diseases were stated to be the most common dental problem. Dental treatments, such as removal of calculus and extractions, were performed by nearly all veterinarians. Fifty per cent of the veterinarians asked for assistance of a dentist when a dental treatment could not be carried out by themselves. More education in veterinary dentistry to veterinary students and veterinarians is required. PMID- 1926097 TI - [Comparative pathology; territory with many streams]. AB - Normal and abnormal situations in the reptilian ovary are reviewed. The normal development of the ovary is mainly governed by the temperature and variations in length of daylight. Vitellogenesis, (the production of yolk) takes place in the liver and is regulated by oestrogens. Under an abnormal light regimen, for instance 12 hours of light--12 hours of darkness, erratic vitellogenesis may occur. Atresia or resorption of follicles may occur at all stages of their development. The pathology of the process of resorption is characterised by the invasion of blood vessels and phagocytosis of yolk by macrophages. Pseudopregnancy is referred to for the first time. An important pathological aspect is the sterile inflammation of the ovary, which is fairly common in reptiles. The pathogenesis most probably is a trauma or some other defect of the egg membrane, resulting in leakage of vitelline into the surrounding fatty tissues. This contact gives rise to a chronic granulomatous inflammation. Comparative pathology covers a very wide field. In the Department of Special Animal Pathology, the specialization known in other areas of the veterinary profession, is directed towards a concentration of staff members on certain groups of animals such as mammals, birds, reptiles and laboratory animals respectively. At thesis was advanced, stating that a problem-solving attitude of the students cannot be solely attained by participation of veterinary students in fundamental research. The department of veterinary pathology is devoted to a problem-solving mode of education of students. PMID- 1926098 TI - [Prolapse of the urinary bladder in cattle]. PMID- 1926099 TI - [Multi-year outlook Agricultural Research 1991-1994 (2)]. PMID- 1926100 TI - [Veterinary Chief Inspection for Public Health. Salmonella enteritidis in poultry: monitoring and control 1990/1991]. PMID- 1926101 TI - [How can the incidence of antibiotic residues in meat animals be minimized?]. AB - The causes of the presence of antibiotic residues in slaughtered animals are analysed. The fact is stressed that the persistence of antibiotic residues in slaughtered animals varies, among other things, with the antibiotic itself, the pharmaceutical design and, in the case of subcutaneous or intramuscular injection, the site of injection and the severity of local irritation of the tissues. There are marked differences between the various antibiotic products as regards the local irritation induced and the residual persistence in organs at the site of injection. A selective use of antibiotics and forms of administration (so-called 'positive list') is advocated, by which the incidence of antibiotic residues in slaughtered animals can be restricted. Recommendations for drawing up a 'positive' list' are made. PMID- 1926102 TI - [A comparison between large breeds of cattle and their cross-breeds with Jerseys]. AB - Friesians (ZB) and MRY cows were inseminated with semen from Jersey or Holstein Friesian (ZB) and Jersey or MRY bulls respectively. The Jersey x Friesian (J x ZB) and the Jersey x MRY (J x MRY) crossbreds were compared with their contemporary Friesian and MRY herdmates, respectively. Crossbreds were born without any calving problems. The feet and legs were better, the mature weight, the feed costs and the average carcass values were lower compared to the purebreds. The conclusions are, that in market situations, where milk production or milk fat production is not limited, the crossbreds yield a much higher return per hectare than the purebreds. The present measures to limit milk fat production do not make crossbreds clearly profitable over Friesians and MRY's in the Netherlands. Also the relative increase for milk protein in relation of milk fat has contributed to that. PMID- 1926103 TI - [Bites in dogs]. PMID- 1926104 TI - [Myiasis in sheep]. PMID- 1926105 TI - [Multi-year outlook Agricultural Research 1991-1994 (3)]. PMID- 1926106 TI - [The educated guess. Considerations in the choice of antibiotics in veterinary medicine]. PMID- 1926107 TI - [Veterinary Chief Inspection for Public Health. The status of rabies in bats in 1990]. PMID- 1926108 TI - [The cat has not always done it. A case of alpha-chloralose poisoning in wild birds]. AB - Neglected hens caused annoyance at a graveyard. Following veterinary advice, the authorities used alpha-chloralose-dressed feed in an attempt to sedate the animals, thus facilitating transport to a more suited place. However, the feed was also consumed by other birds. Moreover, the dosage alpha-chloralose appeared to be too high. Hence the resulting mortality struck both the hens and the wild birds. Obviously, alpha-chloralose should not be used for these applications. PMID- 1926109 TI - [Hereditary eye diseases--diagnosis, therapy and prevention]. AB - Eight hereditary eye diseases are discussed. These eight abnormalities follow the main possible patterns of inheritance. The clinical aspects and the prevention of these illnesses are discussed. PMID- 1926110 TI - [Genetic eye defects in the dog]. AB - Genetically determined disturbances of the normal function of the eye are distributed in high frequencies in several breeds of dogs. Two groups of these disturbances are discussed; disturbances resulting from the aims of breeding and defects caused by mutant genes. Disturbances such as ectropion, entropion and trichiasis may be regarded as the results of aims of breeding. They have a polygenic background and can be reduced by selection against the undesired traits and by modification of the breed standards. The frequencies of defects caused by mutant genes such as PRA, cataract and PHTVL/PHPV can be effectively reduced by veterinary practitioners. They are expected to be able to explain the consequences of breeding with animals carrying these genes to their clients when patients with these defects are presented. PMID- 1926111 TI - ['Good veterinary practice?']. PMID- 1926112 TI - [Effects of long-term BST application in dairy cows]. AB - The effects of administration of BST on milk production of dairy cows are summarised on the basis of a number of review papers. Then the results of a trial with forty control cows and thirty-seven cows, in which six doses of 640 mg of BST were subcutaneously injected at twenty-eight day intervals from the fourth month after calving in a third of fourth lactation are discussed. The response to administration of BST was a 3.2 kg of milk yield, 165 g for milk fat, 105 g of milk protein and 155 g lactose. Efficiency of milk production during the period of treatment was seven per cent higher in the treated cows. During the successive lactations, the response to BST in milk fat slightly declined, but similar responses were recorded for milk protein and lactose. Plasma levels of 3 hydroxybutyrate and NEFA were higher after treatment with BST. Fertility and health were not affected by this treatment. Calves from treated cows showed five per cent lower birth weight, which had no effects on viability and postnatal weight gain. Treatment with BST did not have any effect on the concentrations of calcium, magnesium, phosphorus and NEFA in milk. In the successive lactations, the somatic cell count in the milk of treated cows increased slightly more than that in controls. During the third and fourth lactation, in the period of treatment, the number and percentage of polymorphonuclear neutrophils and number of macrophages were higher in milk showing higher cell counts. More quarters of the udders of treated cows were bacteriologically infected compared to the controls before and after treatment. Small injection sites were detected on 50-60 per cent of the treated cows, which disappeared rapidly. In the third and fourth lactation, no marked differences between controls and treated cows were recorded in frequencies of diseases and culling. PMID- 1926113 TI - [Convulsions in gray red-tailed parrots]. PMID- 1926114 TI - [Veterinarian and BST (Bovine somatotropin)]. PMID- 1926115 TI - [Derailment of basic functions]. PMID- 1926116 TI - [Pathology of the lower airways]. AB - The differential diagnosis in children with dyspnea should be aimed at all systems that support an adequate gas exchange. The diagnosis must be based on history, physical examination and laboratory screening. The diagnosis should be made when the disease is in a non-life threatening phase. PMID- 1926117 TI - [Pathology of the upper airways]. AB - Pathology of the higher airways in children is seen rather often. A child with obstruction of the upper airways has to be examined with extreme caution and treated without delay. The main causes of obstruction of the higher airways are the infections of the airways, especially epiglottitis and laryngotracheobronchitis. PMID- 1926118 TI - [Shock in children; no child's play]. AB - Shock comprises of circulatory insufficiency accompanied by a discrepancy between oxygen demand and supply at tissue level. This results in tissue hypoxia, which when persisting, can lead to (severe) organ failure. In this article we will discuss pathophysiologic backgrounds of shock following the mechanisms that cause hemodynamic deterioration and tissue hypoxia. Subsequently the role of various cytokines in the pathogenesis of septic shock, which occurs relatively frequent in childhood, are discussed. As far as fluid substitution and vasoactive medication is concerned, therapeutic strategies can be chosen more rationally these days. This is mainly due to the availability of smaller i.v. cannula, central venous catheters and advances in (non) invasive hemodynamic measurements in childhood e.g. central venous pressure, cardiac output, peripheral vascular resistance and left ventricular shortening fraction. Despite these developments, shock (in particular septic shock) remains to have a high mortality, also in childhood. PMID- 1926119 TI - [Artificial ventilation, a special interaction of pulmonary mechanics and gas exchange]. AB - During artificial ventilation the lungs are intermittently insufflated by respiratory gases in a certain pattern (ventilatory conditions). The consequences in terms of stretch of lung tissue, airway pressure, alveolar pressure and gas exchange depend on the mechanical properties of airways, lung tissue and thoracic wall. These properties are age dependent and may be changed considerably by disease. The basic principles of ventilatory support can be explained as an interaction of ventilatory gases passing through the airways in and out of the lungs, the subsequent changes in stretch of lung tissue and thoracic wall and pressure variations in the airways and alveoli. Overstretched lung and airways tissue causes damage (barotrauma, air leakage). During artificial ventilation intrathoracic pressure increases, which diminishes venous return to the heart and decreases cardiac output. In addition, the sometimes inevitably high oxygen concentrations may be toxic. In this article the ventilatory cycle is analysed into its different sequences and the interaction with the respiratory system and its consequences are discussed. PMID- 1926120 TI - [Hyponatremia and hypernatremia]. PMID- 1926121 TI - [The pediatrician and the surgical patient]. AB - Knowledge of the specific reaction pattern of the developing organ system on surgical interventions is essential for the management of surgical problems in infants and children. Pediatricians and surgeons should combine the knowledge of their own field for successful treatment. The pediatrician is able to give an essential contribution to the treatment of the infant with congenital anomalies, underlying illnesses interfering with surgery, total parenteral nutrition and perioperative fluid therapy. PMID- 1926122 TI - Detection of anti-epithelial cell antibodies in association with pediatric renal transplant failure using a novel microcytotoxicity assay. AB - We have developed a microcytotoxicity assay allowing sera to be screened for anti epithelial cell cytotoxic antibodies. Cells from the epithelial cell line A549 were cultured overnight in Terasaki trays prior to the addition of the sera to be screened. Using this assay, 63 pediatric recipients of 78 renal transplants have been studied retrospectively. Seventeen transplants carried out in 13 patients were found to be associated with the production of antibodies reactive only against epithelial cells (AEC). Eleven of these transplants failed as compared with 19 failures out of 52 transplants not associated with AEC production (Fisher's p = 0.04). We conclude that transplantation in the face of pre-existing AEC should be approached with caution. PMID- 1926123 TI - No association between susceptibility to multiple sclerosis and HLA-DPB1 alleles in the French Canadian population. AB - HLA-DPB1 typing was performed using polymerase chain reaction DNA amplification and sequence-specific oligonucleotide probing (PCR-SSOP) which permitted identification of 17 distinct DPB alleles using 15 oligonucleotide probes. The accuracy of this approach was confirmed in an initial study of 26 human B lymphoblastoid cell lines which demonstrated close agreement between PCR-SSOP and PLT assigned types. A cohort of 47 adult French Canadians was then studied to provide an estimate of DPB1 allelic frequencies in an ethnically homogeneous population. DPB1*0401 was the most frequent phenotype (61.5%) and only DPB1*0101, 0301 and 0402 were also present at frequencies greater than 10%. HLA-DPw4 has been reported to be associated with multiple sclerosis (MS) but our PCR-SSOP analysis of 52 French Canadian MS patients showed no association with either the DPB1*0401 or DPB1*0402 splits of DPw4 or with any other DPB1 allele. PMID- 1926124 TI - Oligonucleotide typing analysis for the linkage disequilibrium between the polymorphic DRB1 and DRB5 loci in DR2 haplotypes. PMID- 1926125 TI - Novel HLA-DR2 and -DR3 haplotypes among Norwegian Caucasians. AB - In the Northern European population, all DR2 haplotypes encoded by DRB1*1501 have previously been found to carry the DQA1*0102 and DQB1*0602 alleles, and DR3 haplotypes have been found to carry the DQA1*0501 and DQB1*0201 alleles. Here we report a novel recombinant DR2 haplotype carrying the DRB1*1501, DQA1*0102 and DQB1*0603 alleles as well as a novel recombinant DR3 haplotype carrying the DRB1*0301, DRB3*0101, DQA1*0102 and DQB1*0602 alleles. PMID- 1926126 TI - HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genes in Japanese multiple sclerosis patients. AB - Japanese MS patients and controls were examined for the distribution of HLA-DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 alleles using in vitro amplification of genomic DNA and probing with sequence-specific oligonucleotides. No significant difference in frequency of the examined alleles was observed among the two groups. This is in contrast to Norwegian MS patients, where an association to a combination of certain DQA1 and DQB1 alleles has previously been demonstrated. PMID- 1926127 TI - HLA class I nucleotide sequences, 1991. AB - The HLA Class I sequences included in this compilation are taken from publications listed in the papers: Nomenclature for factors of the HLA system, 1990 (1) and Nomenclature for factors of the HLA system, 1989 (2). Where discrepancies have arisen between reported sequences, the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments, identity between residues is indicated by a hyphen (-). An unavailable sequence is indicated by a period (.). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number. PMID- 1926128 TI - HLA class II nucleotide sequences, 1991. AB - The HLA Class II sequences included in this compilation are taken from publications listed in the papers: Nomenclature for factors of the HLA system, 1990 (1) and Nomenclature for factors of the HLA system, 1989 (2). Where discrepancies have arisen between reported sequences, the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments, identity between residues is indicated by a hyphen (-). An unavailable sequence is indicated by an asterisk (*). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number. PMID- 1926129 TI - HLA class II-associated genetic susceptibility in multiple sclerosis: a critical evaluation. AB - Multiple sclerosis (MS) has, since the 1970s, been known to be associated with the HLA-Dw2 and -DR2 specificities in Caucasian Europeans and North Americans. By the use of genomic typing techniques, the association has been specified to be with the DRw15,DQw6,Dw2, i.e. the DRB1*1501-DQA1*0102-DQB1*0602 haplotype. A significant DPw4 association in Scandinavian MS patients has been described in one report. However, this association has not been confirmed in several subsequent studies with patients from the same and other ethnic groups. During the last few years several reports, based on serological, RFLP and PCR-SSO data, have suggested that the HLA class II-associated MS susceptibility gene(s) may be more closely associated with the DQ than with the DR subregion. The observations that the HLA-DQB1 genes of MS patients share long stretches of sequence motifs and also carry DQA1 alleles encoding glutamine at position 34 of the DQ alpha chain have received considerable attention. It has been suggested that the susceptibility to develop MS might be determined by the corresponding DQ alpha beta heterodimers either encoded in cis or in trans. We have investigated these issues in a large group of Swedish MS patients (n = 179). We found that the associations with the suggested DQB1 sequences and position 34 of the DQ alpha chain were due to linkage disequilibrium and secondary to the association with the DRw15,DQw6,Dw2 haplotype (p less than 10(-9) and p less than 10(-8), respectively). No overrepresentation of the implicated DQ alpha-beta heterodimers was observed in DRw15,DQw6,Dw2-negative patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1926131 TI - HLA associations with autoimmune Addison's disease. PMID- 1926130 TI - DNA typing for HLA-DR, and -DP alleles in a Chinese population using the polymerase chain reaction (PCR) and oligonucleotide probes. AB - We have determined alleles of HLA-DRB1, DRB3, DRB5, DQA1, DQB1, and DPB1 loci in 91 unrelated healthy individuals from North China. Group-specific PCR primers were employed for the analysis of subsets of DR1, DR2, DR4, DRw52, and DPB. With allele-specific probes, 22 DRB1, 8 DQA1, 13 DQB1, and 12 DPB1 alleles were found in this panel. Allele frequencies showed that 25.3% of the subjects had DR7 and 26.4% had DR9, only 5.5% had DRB1*0301 (DRw17). In the DR4 group, DRB1*0405 (Dw15, 8.8%) and 0406 (KT2, 9.9%) were the most prevalent alleles. DRB1*0404 (Dw14.1), 0407 (Dw13.2) and 0408 (Dw14.2) were absent and the other alleles of the DR4 group were rare. The most common DRw6 subset was DRB1*1401 (8.8%). DRB1*0802 and 0803 were present (2.2%, 6.6%), and DRB1*0801 was not found. Associations with DQA1 and DQB1 were generally similar to those found in other populations. DPB1*0501 was the most frequent (60.2%) allele at the DPB1 locus. Overall our study shows that the distribution of class II alleles in a population from Mainland China is quite different from other ethnic groups. The high frequency of the KT2 subset of DR4. (DRB1*0406) and of DPB1*0501 are the most striking features found. A new type of DR4 was determined in one subject. It was like DR4-Dw15 (DRB1*0405) but, according to our hybridization patterns, it encoded valine instead of glycine in position 86. It is now called DRB1*0410. PMID- 1926132 TI - Different HLA DR2-DQw1 haplotypes in Sardinian and northern Italian populations: implications for multiple sclerosis susceptibility. PMID- 1926133 TI - Local analysis of 11th International Histocompatibility Workshop PCR oligonucleotides for HLA-DQ in a population of Inuits. PMID- 1926134 TI - Abundance of DR2/DR3 and DR2/DR7 heterozygotes in Caucasian patients with systemic lupus erythematosus from USA. PMID- 1926136 TI - Detection of endothelin-like immunoreactivity in epithelium and fibroblasts of the human umbilical cord. AB - We studied tissue sections of freshly obtained full-term and premature human umbilical cords using polyclonal antibody to endothelin and immunocytochemistry. Endothelin immunoreactivity was detected in the cytoplasm of epithelial cells and primitive fibroblasts, but not in the endothelial cells of both full-term and premature umbilical cords. Immunoelectron microscopy using indirect immunogold staining technique localized endothelin immunoreactivity to the cytoplasm of the epithelial cells and fibroblasts but not confined to any particular structures. No endothelin immunoreactivity was detected in the nucleus or on the cell membrane. Pre-absorption tests with synthetic endothelin-1, -2, and -3 independently established that the immunoreactivity represented endothelin-1 and 2, but not -3. The presence of endothelin-1 and -2-like immunoreactive materials in epithelial cells and fibroblasts of human umbilical cord suggests a role of endothelin in parturition. PMID- 1926135 TI - Immunocytochemical localization of laminin in hamster tracheal epithelial cell cultures. AB - EM examination of 28 day cultures of enzymatically dissociated hamster tracheal epithelial (HTE) cells grown on collagen coated millipore filters reveals that fragments of basal lamina may be present at the basal plasmalemma. Since the basal lamina consists of several major components including type IV collagen, heparan sulfate proteoglycans, entactin/nidogen, and laminin, questions naturally arise concerning the presence of such a structure in this cell culture system. When immunocytochemical procedures utilizing anti-laminin antibody and PAP techniques are carried out with paraffin sections of HTE culture at 1,2,3, and 4 weeks in vitro, LM analysis reveals that a thin, dense line of reaction product is present between the basal surface of the HTE cells and the underlying collagen substrate. Immunoblotting evaluation carried out with supernatants of 7d HTE cell homogenates and HTE cell conditioned media also indicate that laminin is being produced by the tracheal cells. Thus, the presence of basal lamina-like fragments, the immunocytochemical localization of laminin, and immunoblot identification of laminin in hamster tracheal epithelial cell cultures, suggest that, although basal lamina components may be produced by HTE cells, at the time points tested, they are not yet being organized into a complete basal lamina. PMID- 1926137 TI - Direct cell-cell communication in the blood-forming system. AB - In mammals, bone marrow is the principal tissue where blood is formed during adult life. Paracrine factors are generally considered to control this process but there is considerable evidence that gap junctions are present in haemopoietic tissues. Gap junctions have been implicated in developmental and patterning roles, and we set out to characterize the cells which are coupled, and to provide evidence for their role(s) in blood cell formation. Direct cell-cell communication, shown by dye-transfer, occurs between haemopoietic cells and certain stromal cells. In culture these stromal cells form a mat in which they retain their dye-coupling properties. Freeze-fracture electron microscopy confirms that this coupling is via gap junctions. When haemopoietic cells are cultured on top of these mats dye spreads upwards from the stromal cells into the haemopoietic cells above. Experiments in which haemopoietic cells were cultured alone, with stromal cell conditioned medium, or in direct contact with stromal cell underlays, were therefore carried out. The results of these experiments provide evidence that gap junctional communication may be playing a vital role in maintaining populations of precursor cells which would otherwise differentiate into end cells, leading to the ultimate demise of the system. PMID- 1926138 TI - Release of cytoplasmic apical protrusions from principal cells of the cat epididymis, an electron microscopic study. AB - Epididymides of captive normal adult cats were studied by light and transmission electron microscopy. Release of apical portions of principal cells occurred by a process of pinching-off. The membrane-bound bodies (spherules) formed were then found in the epididymal lumen. We postulate that this represents an apocrine secretion process. Such phenomenon were present in all segments of the epididymis, whether caput, corpus, or cauda. Rows of microvesicles similar to those described in other species were also observed between microvilli. The mechanism of formation of spherules and microvesicles seemed to be formed by a different mechanism. PMID- 1926139 TI - The egg-shell of Drosophila melanogaster. VI, Structural analysis of the wax layer in laid eggs. AB - Utilizing freeze-fracturing conventional electron microscopy and scanning electron microscopy methods, a wax layer was identified, sealing the oocyte of Drosophila melanogaster. In mature egg-shells wax forms a hydrophobic layer surrounding the oocyte and lying between, and in very close contact with the vitelline membrane (interiorly) and the crystalline intermediate chorionic layer (exteriorly). In cross-fractured views it is less than 50 A thick whereas in longitudinal fracturing it reveals smooth fracture faces of a multilayered material in the form of hydrophobic areas or plaques (0.5-1 microns in diameter) which are partially overlapping and highly compressed between the vitelline membrane and the innermost chorionic layer. The evidence for this layer being a wax are the facts that a) it is not preserved in conventional fat-extracting electron microscopy methods, b) it directs laterally the fracture planes during freeze-fracturing and reveals smooth fracture faces. Analysis of the structural features of wax in mature egg-shell in various species of Drosophilidae have shown that the wax layer exhibits indistinguishable (among the species) hydrophobic plaques, which have the same size and thickness with Drosophila melanogaster. These data provide structural evidence explaining the physiological resistance of the insect eggs studied, against water loss or water uptake, whenever they are laid on substrates with extreme environmental conditions. In addition, the data demonstrate how an extracellular substance can be organized to perform that function. PMID- 1926140 TI - Control of follicular epithelium development and vitelline envelope formation in the mosquito; role of juvenile hormone and 20-hydroxyecdysone. AB - Using microsurgical manipulations, hormone applications, and transmission electron microscopy we have investigated the regulation of differentiation of the follicular epithelium and formation of the vitelline envelope (VE) in primary follicles in the ovary of the mosquito, Aedes aegypti. During the first 3 days after eclosion, the primary follicle grows, and cells of the follicular epithelium differentiate, their content of mitochondria, rough endoplasmic reticulum, and Golgi complexes increases significantly. Growth and differentiation of the follicular epithelium appear to be under the control of juvenile hormone (JH), because they are blocked by removal of corpora allata in newly closed adult females and can be restored by either implantation of corpora allata or application of JH III. In insects, including mosquitoes, VE is the first layer of the eggshell to be deposited. It is formed from the secretory products of the follicle cells and its deposition coincides with yolk accumulation by developing oocytes. Only follicle cells adjacent to the oocyte deposit VE. In decapitated females, given a blood meal by enema and injected with picogram doses of 20-hydroxyecdysone (20-HE), follicle cells synthesize the VE precursors and deposit morphologically normal VE, in contrast to saline injected controls which deposit no VE. We conclude that 20-HE, as well as factors originating from the blood meal and the oocyte, are required for the normal formation of VE in the mosquito follicles. PMID- 1926141 TI - Reaction of mononuclear cells from patients with bronchial asthma to Candida albicans. AB - This study was undertaken to investigate cytokine production of mononuclear cells (MNCs) from patients with bronchial asthma stimulated by antigens of Candida albicans in vitro. The reaction of MNCs from corticosteroid-dependent patients was restricted to a low level. The level of tumor necrosis factor (TNF)-alpha released into the culture fluid was significantly higher in the high responders (HR) of the atopic corticosteroid-independent (A-CSID) group than those of other asthmatic and control groups (p less than 0.01). The level of IL-1 beta of the A CSID group was significantly higher than that of the non-atopic corticosteroid independent group (p less than 0.05), but not significantly different from the controls. In HR of the A-CSID group, the production of TNF-alpha and IL-1 beta was augmented and interferon-gamma production was also increased in these patients. These results suggest that Candida albicans can contribute to the augmentation of cytokine production in bronchial asthma, especially in some of atopic type. PMID- 1926143 TI - The effect of kallikrein on human sperm membrane function. AB - To illustrate the influence of kallikrein on the hypoosmotic swelling test, 84 human semen samples were classified into 4 groups: normospermia (n = 34, group A), oligospermia (n = 18, group B), asthenospermia (n = 8, group C), and oligoasthenospermia (n = 24, group D). Two aliquots of 0.45 ml were prepared from each specimen in all the groups: one was incubated for 3 hr in a glass tube containing kallikrein and the other was incubated without kallikrein (control). Quantitative and qualitative assessment of sperm motility and the hypoosmotic swelling test (HOST) were subsequently performed in each pair of samples. Percentage of motile spermatozoa, speed of forward progression of motile spermatozoa and the percentage of swollen sperm were significantly lower in the control samples than in samples treated with kallikrein in all the groups. Kallikrein was also proved effective in increasing the outcome of the HOST, the percentage of motile spermatozoa and the speed of forward progression of washed spermatozoa received from normospermic men (n = 15). It seems that kallikrein has a direct effect on sperm membrane and improves its properties and functions. PMID- 1926142 TI - Metallothionein concentrations and organ retention of mercury in the liver and kidney of the neonatal guinea pig after exposure to mercury vapor. AB - Neonatal guinea pigs were exposed to mercury vapor on the day of birth, and the following mercury distribution and concentrations of metallothioneins (MTs) in the liver and kidney were observed. In the liver, two hours after exposure, an appreciable amount of mercury accumulated and a substantial portion of this was associated with MTs. During postnatal development, the mercury concentration increased, whereas the hepatic concentration of MTs decreased. The mercury in the soluble fraction of the liver shifted from the region of MTs to the high molecular-weight region and, finally, the mercury peak in the MT region was not detected. The kidney mercury concentration was high even 2 hr after the exposure and on days 3 and 7 postpartum. The peak concentration was observed on day 3 postpartum. The mean renal concentration of MTs in the mercury-exposed neonates was significantly higher than that of the control at all times observed. The changes in both the mercury level and the concentration of MTs were strongly correlated. Furthermore, most mercury in the soluble fraction was associated with MTs on day 7. These findings indicated enhanced synthesis of MTs in the kidney, but not in the liver, after mercury vapor exposure in the neonatal period, with corresponding elevated copper and zinc concentrations in the kidney. PMID- 1926144 TI - Triethylene-tetramine (trien) therapy for Wilson's disease. AB - Triethylene tetramine (trien), in increasing dose from 1.0-2.0 g/day to 2.5-3.0 g/day, was used for 4 Japanese patients with Wilson's disease who were intolerant of D-penicillamine (D-PC). Before the treatment, urinary copper excretion (UCE) was 70-96 micrograms/day. UCE increased to 1,512-2,352 micrograms/day on the day of initial administration, and remained at levels between 350-1,100 micrograms/day, thereafter. During 2 months of trien therapy, neurological deficits regressed in three patients, and only slightly in one patient. No adverse effects were observed. These results and the retrospective survey on 17 patients treated with D-PC confirmed that trien is less potent but a safer copper chelating agent than D-PC. The transient aggravation of neurological deficits seen in two patients during the early stage of the treatment suggested that trien, as D-PC, should be started in small doses and gradually increased. PMID- 1926145 TI - Bone formation on synthetic precursors of hydroxyapatite. AB - The aim of this study was to investigate the reaction of skeletal tissue to various synthetic calcium phosphate (Ca-P) compounds in vivo. Five synthetic Ca-P compounds were implanted into the subperiosteal area of the calvaria of 7-week old BALB/c mice for one to 15 weeks. Synthetic compounds were dicalcium phosphate (DCP), octacalcium phosphate (OCP), amorphous calcium phosphate (ACP), Ca deficient hydroxyapatite and hydroxyapatile (HA). Implanted DCP, OCP and ACP were found to be converted to apatitic phase by x-ray microdiffraction analysis using undecalcified specimens. Structure of bone was found out on all of Ca-P compounds eventually at late stage under the light microscope, but the rate of bone formation calculated from a number of experiments varied on respective synthetic Ca-P compound. It was high as 80% for DCP, OCP and ACP, but was low as 5.6% for Ca-deficient HA, and no reaction was found for HA at the stage of 3 weeks. Fine filaments and granular materials in the newly formed bone matrix were detected at 7 days around the remnants of OCP particles which already converted to apatitic phase by ultrastructural study of decalcified specimens. These structures were very similar to the components of bone nodules seen in intramembranous osteogenesis. It is postulated that the precursors of HA have an important role in intramembranous osteogenesis. PMID- 1926146 TI - Simultaneous analysis of the patterns of nuclear DNA and cell protein contents in pancreatic carcinoma with reference to prognosis. AB - Simultaneous analysis of the patterns of nuclear DNA and cell protein contents was performed in 13 patients with pancreatic carcinoma to evaluate their prognostic significance. The patients were divided into two groups according to clinical outcome. Namely, six died of the primary disease within one year (group A), and six survived longer than 16 months and one died of other cause (liver abscess) at 9 months after operation (group B). The cell suspensions prepared from paraffin-embedded specimens were stained with diamidino-phenylindole and hematoporphyrin for nuclear DNA and cell protein, respectively. Fluorescence intensities of 20 lymphocytes as control and 200 carcinoma cells of each case were measured. The nuclear DNA pattern was mainly diploid or tetraploid in group B. Group A showed aneuploid and polyploid patterns. Furthermore, mean DNA content of group A was significantly higher than that of group B. Cell protein content was widely scattered and higher in group A than group B. Analysis of nuclear DNA ploidy, relative value of DNA and cell protein content may be a reliable tool to predict prognosis of patients with carcinoma of the pancreas. PMID- 1926147 TI - Histological study of pulmonary vasculature in fatal cases of persistent pulmonary hypertension of the newborn. AB - Using our own morphometric technique, we examined pulmonary vasculature in eight neonates who died of persistent pulmonary hypertension of the newborn (PPHN). PPHN was judged to be idiopathic in three neonates and was associated with fatal meconium aspiration in the other five. Two characteristic structural features of PPHN were revealed in this study. First, medial thickening of the normally fully muscularized pulmonary vessels occurred in the smaller and more peripherally located arteries. Second, fully-muscularized vessels extended as far as the intraacinar arteries, which are normally non-muscular vessels at this age. This structural abnormality appears not to merely represent a failure of the fetal pattern to regress, and it is suggested that PPHN is due to a structural abnormality of the pulmonary microcirculation in fatal cases. PMID- 1926148 TI - Effects of indomethacin in utero on the pulmonary vasculature of the newborn lambs. AB - Exposure of the fetus to indomethacin and the resultant closure of the ductus arteriosus in utero has been suggested to be one possible cause of persistent pulmonary hypertension of the newborn (PPHN). We examined whether or not closing the ductus arteriosus of fetal lambs by the administration of in-domethacin to the fetus and ewe could produce the functional and structural changes of PPHN. Three treated and four non-treated lambs were delivered by cesarean section. Postnatal hemodynamics were studied in two of the treated lambs. Pulmonary arterial pressure gradually decreased after delivery and did not reveal features compatible with PPHN, while the blood gases remained within the physiological range. However, acute hypoxemia produced a re-elevation in pulmonary arterial pressure. Morphometric analysis showed the medial thickening of normally fully muscularized pulmonary arteries, but there was no abnormal extension of fully muscularized arteries to the intraacinar level in the treated lambs. In conclusion, we could not reproduce functional and structural changes of PPHN in newborn lambs by the administration of indomethacin in utero. However, our experimental animal model with excessive muscularization of the pulmonary vasculature appears to be useful for studying vasoconstriction in response to hypoxemia. PMID- 1926149 TI - Changes of duodenal pH and pancreatic exocrine function after upper G-I intraluminal ethanol administration. AB - Using 3 outbred dogs with pancreatic, gastric and jejunal fistulas, we examined changes in pancreatic exocrine secretion, duodenal pH and plasma CCK concentration after intragastric or intrajejunal administration of ethanol. Intragastric administration of 20% or 40% ethanol significantly lowered the pH in the duodenal cavity, and pancreatic fluid secretion and bicarbonate excretion were stimulated. Intrajejunal administration of ethanol elicited stronger responses. Plasma CCK concentration was not changed or was only slightly lowered by ethanol administration in the digestive tract. It is assumed that stimulation of pancreatic exocrine secretion was mediated by the secretion of gastric acid. PMID- 1926150 TI - The cerium-induced liver injury and oxidative drug metabolism in DBA/2 and C57BL/6 mice. AB - The influence of the known hepatotoxic agent, cerium (Ce) on the activity of liver microsomal monoxygenases, especially coumarin 7-hydroxylase (COH) was investigated in two inbred strains of male mice, DBA/2N and C57BL/6N. Ce was injected intravenously in three doses (0.5, 1.0 and 2.0 mg/kg body wt) and the animals were killed 24 or 72 h later. On the basis of histological assessment of the liver, C57BL/6N mice are apparently more resistant to the hepatotoxic effect of Ce. At 24 h, COH activity was increased in a dose-dependent manner in DBA/2 animals, whereas no change was seen in C57BL/6N animals. A significant increase in all other enzymes studied, cytochrome P-450 (P450), ethoxycoumarin O deethylase and ethoxyresorufin O-deethylase, was seen in DBA/2 mice injected with the highest dose of Ce. At 72 h Ce increased CON activity, as well as other enzymes, in C57BL/6N mice in a dose-dependent manner, whereas in DBA/2 mice the increase was only seen after the two lower doses, the highest dose causing severe morphological changes in the liver structure and a clear decrease in COH and other activities. The distribution studies with Ce-141 showed that C57BL/6N livers contained more Ce than DBA/2 livers after the highest dose. PMID- 1926151 TI - Cytoprotective effect of reduced glutathione in arsenical-induced endothelial cell injury. AB - The effect of four arsenic compounds on cultured endothelial cell isolated from bovine carotid arteries was studied. Only trivalent arsenicals (arsenic trioxide and sodium m-arsenite), but not pentavalent arsenicals (arsenic acid and p arsenilic acid), induced significant cell injury. Since the intracellular reduced glutathione (GSH) plays an important role in detoxication in mammalian cells, its effect on arsenical-induced cell injury was then studied. Pretreatment of cells with 500 microM GSH not only resulted in several-fold increase in the intracellular level of GSH but also effectively protected them against the injury caused by arsenic trioxide. After a pretreatment of cells with GSH for 3 h, the intracellular GSH reached a plateau. A longer pretreatment for 24 h still kept GSH at a very significant high level. The cell injury induced by arsenic trioxide was protected by GSH, and then cellular biosynthesis of PGI2 in culture was also increased. The cytoprotective effect and the stimulatory effect on PGI2 production, where both were dose-dependent on GSH, were in a strict reverse relationship. Aspirin treatment inhibited the PGI2 biosynthesis induced by GSH in the arsenic trioxide-induced cell injury, and significantly reduced the cytoprotective effect induced by GSH. These results suggest that the marked stimulation of endogenous PGI2 biosynthesis by GSH is the mechanism of the latter's cytoprotective effect on arsenic trioxide-induced endothelial cell injury. PMID- 1926152 TI - Effects of organic solvent vehicles on the viability and morphology of isolated perfused porcine skin. AB - Although many organic solvents are known to be cutaneous irritants, they are commonly utilized as vehicles in percutaneous absorption and toxicity studies. The isolated perfused porcine skin flap (IPPSF) is an alternative animal model that has been used to study percutaneous absorption and cutaneous toxicity. The purpose of this study was to evaluate the effect of five organic solvents (ethanol, acetone, dimethyl sulfoxide (DMSO), toluene, and cyclohexane) on biochemical viability parameters, vascular response, and epidermal morphology of the IPPSF. Cumulative glucose utilization (CGU), the ratio of lactate production/glucose utilization (L/CGU ratio), and the leakage of lactate dehydrogenase (LDH) were used as biochemical indicators of alterations in glucose metabolism and flap viability. Only ethanol resulted in a statistically significant decrease in the average rate of CGU over the perfusion period. All of the solvent treatments resulted in slight increases in LDH release versus the controls. Vascular resistance (VR) was measured to examine the response of the cutaneous vasculature to these solvents, and most treatments resulted in a decreased VR in the terminal phases of perfusion. Ethanol was the only solvent to cause an apparent increase in terminal VR. Light microscopy demonstrated a moderate increase in intracellular edema in the DMSO, toluene, and acetone flaps. Ultrastructural evaluation showed focal blebbing of the nuclear envelope and vesiculation of the rough endoplasmic reticulum in cells of the stratum basale and stratum spinosum layers with DMSO treatment. The IPPSF allowed the evaluation of subtle biochemical, vascular, and morphological changes associated with non occlusive topical exposure to these organic solvents. These findings support the necessity of documenting vehicle effects which might mask or otherwise alter subtle, but potentially important, compound-specific responses. PMID- 1926153 TI - Neonatal exposure to 3,3',4,4'-tetrachlorobiphenyl: changes in spontaneous behaviour and cholinergic muscarinic receptors in the adult mouse. AB - We have previously reported that 3,3',4,4'-tetrachlorobiphenyl (TCB) affects muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice at the age of 10 days. As shown in the present study, such early exposure to TCB may also lead to a permanent change in the MAChR and disturbed behaviour of the mice as adults. Male NMRI mice were given two single oral doses of TCB, 0.41 or 41 mg/kg body wt, and a 20% fat emulsion vehicle (10 ml)/kg body wt. The behavioural test at adult age of 4 months indicated a significant change in spontaneous motor behaviour in the TCB-treated mice. In mice receiving the highest dose of TCB there was also a minor increase (5%), although significant, in the density of MAChR in the hippocampus, assayed by using the tritium-labeled muscarinic antagonist, quinuclidinyl benzilate [( 3H]QNB). As previously reported, this part of the brain was affected in the neonatal mouse, which shows that the cholinergic system during rapid development in the neonatal mouse brain is sensitive to disturbance. This may lead to permanent changes in the animals as adults, accompanied by behavioural changes. PMID- 1926154 TI - Dermal intoxication of mice with bis(2-chloroethyl)sulphide and the protective effect of flavonoids. AB - The influence of dermal application of sulphur mustard (SM) on hepatic lipid peroxidation and the protective effect of flavonoids in SM toxicity was investigated. SM applied on the skin of mice (0.25 or 0.5 LD50) depleted glutathione (GSH) in blood and liver. Malondialdehyde (MDA) levels in the liver showed an increase indicating lipid peroxidation. Administration of vitamin E or two flavonoids, gossypin (GN) and hydroxyethyl rutosides (HR) after dermal application of SM did not alter depletion of GSH but did reduce the MDA level significantly. Survival time of mice with 1 LD50 SM applied dermally was increased by GN and HR to a greater extent than by vitamin E or sodium thiosulphate probably due to one or more of the analgesic, anti-inflammatory, antihepatotoxic, antihistaminic, mast cell stabilization, lipid peroxidation inhibitory and free radical scavenging actions of the flavonoids. The present study indicates that dermally applied SM can induce lipid peroxidation and GSH depletion, and flavonoids may be beneficial in reducing the toxicity. PMID- 1926155 TI - Lack of induction of hepatic DNA damage on long-term administration of peroxisome proliferators in male F-344 rats. AB - In order to evaluate the relationship between hydrogen peroxide (H2O2) generation and subsequent DNA damage caused by peroxisome proliferation, we examined DNA damage and changes in peroxisomal beta-oxidation activity in rat liver. Male F 344 rats were given orally clofibrate, bezafibrate or di(2-ethylhexyl)phthalate (DEHP) for up to 78 weeks. In rats fed DEHP for 52 or 78 weeks hepatocarcinomas or neoplastic nodules were found. In rats treated for 2 weeks with peroxisome proliferators, peroxisomal beta-oxidation activity was increased 10-17 times over control levels. After long-term treatment (20-78 weeks), the level of peroxisomal beta-oxidation activity remained 3-13-times higher in each group. When single strand DNA breaks were measured by a DNA-alkaline elution technique, no increase in DNA damage was observed in livers from rats fed peroxisome proliferators for 2, 40 or 78 weeks. In rats bearing hepatocarcinomas induced by DEHP, the hepatic DNA showed significant breaks; the rate of DNA-alkaline elution was found to increase approximately 5-fold. No significant increase in hepatic lipid peroxide level was observed in each group. These results show that although prolonged treatment with peroxisome proliferators induces markedly peroxisomal beta oxidation activity, the active oxygen species from peroxisomal beta-oxidation are not enough to give rise to significant DNA damage. Moreover, the change in the activity of peroxisomal beta-oxidation may not relate to hepatocarcinogenesis induced by peroxisome proliferators. PMID- 1926157 TI - Reactive oxygen species and non-peroxidative mechanisms of cocaine-induced cytotoxicity in rat hepatocyte cultures. AB - Primary short-term cultures of hepatocytes derived from phenobarbital-induced male Sprague-Dawley rats were used to investigate the mechanisms of cocaine induced cytotoxicity. Exposure of cells to cocaine resulted in a time and concentration-dependent release of lactate dehydrogenase (LDH) into the culture medium which became evident after 7 h of incubation. Over the course of 24 h incubation with cocaine (0.3 mM) there was no significant lipid peroxidation (measured as the formation of thiobarbituric acid-reactive substances. TBA-RS). The addition of the ferric iron chelator, deferoxamine (DFO), prevented in part cocaine-induced LDH release. Alternatively, addition of the antioxidant, alpha tocopherol polyethylene glycol 1000 succinate (TPGS), did not protect against hepatocyte injury. Depletion of the intracellular glutathione (GSH) with diethyl maleate (DEM) to below critical levels for antioxidative protection markedly accelerated the onset and increased the extent of cocaine-induced LDH release, concomitant with massive production of lipid peroxidation. During the first four hours of incubation DFO and TPGS protected against cocaine-induced cytotoxicity in GSH-depleted cells. However, at later stages (24 h), the protective effect was lost even in the absence of lipid peroxidation. These results suggest that reactive oxygen species are involved in cocaine-mediated hepatocyte injury. However, lipid peroxidation can be dissociated from other, non-peroxidative, iron dependent mechanisms of oxidative cell injury. PMID- 1926156 TI - Cadmium toxicity: unique cytoprotective properties of alpha tocopheryl succinate in hepatocytes. AB - Rat hepatocyte suspensions were exposed to toxic concentrations of cadmium (Cd) in the presence and absence of unesterified alpha-tocopherol (T) or alpha tocopheryl succinate (TS). The exogenous administration of TS completely protected hepatocytes from Cd-induced injury and lipid peroxidation. However, hepatocytes exposed to T were not protected from the toxic manifestations of cadmium even though this treatment resulted in a rapid marked accumulation of cellular T. The rate of cadmium uptake by hepatocytes was not significantly altered by exogenous TS or T treatment. These studies indicate that TS cytoprotection against Cd toxicity results not from alterations in Cd uptake or the accumulation of T but rather from the cellular presence of the intact TS molecule. The data also indicate that the depletion of cellular T is not the critical cellular event that is responsible for Cd-induced injury. Instead it appears that TS possess unique cytoprotective properties that intervene in the critical cellular events that lead to Cd toxicity. Thus, TS administration represents a promising new strategy for the mechanistic study and prevention of tissue damage resulting from Cd exposure. PMID- 1926158 TI - Protective effects of dextran sulfate and polyvinyl sulfate against acute toxicity of paraquat in mice. AB - The protective effects of sodium dextran sulfate (SDS) and potassium polyvinyl sulfate (PPS) against the acute toxicity of paraquat (PQ) in mice were studied. The survival rates of mice treated with SDS (2000 mg/kg) or PPS (2000 mg/kg) immediately after PQ ingestion (200 mg/kg) were 100% or 100%, respectively. When treated with SDS (2000 mg/kg) or PPS (2000 mg/kg) 15 or 30 min after PQ ingestion (200 mg/kg), the survival rates were 83% or 67% for SDS-treated groups and 67% or 33% for PPS-treated groups, respectively. Treatment with SDS (2000 mg/kg) or PPS (2000 mg/kg) immediately after oral administration of PQ (200 mg/kg) increased the fecal excretion of PQ, decreased the urinary excretion of PQ and decreased the contents of PQ in the lung, liver and kidney. Such effects of SDS and PPS were reduced in the treatment with these drugs at 15 min after PQ. The in situ small intestinal absorption of PQ was significantly reduced in the presence of SDS or PPS. The binding of PQ to SDS or PPS was determined by an ultrafiltration method. These results indicate that SDS and PPS inhibit the gastrointestinal absorption of PQ on the basis of the increased intestinal transit of PQ and the binding of PQ to the drugs resulting in the protective effectiveness of SDS and PPS on the acute toxicity of PQ. PMID- 1926159 TI - Clostridium difficile toxin A and its effects on cells. AB - Clostridium difficile toxin A in its native form is a high molecular weight (520 540 K) aggregate with five major biological activities. It is lethal, enterotoxic, cytotoxic and cytotonic, and induces hemagglutination of rabbit red blood cells. Possibly these activities are contained in separate components. A major subunit of c. 230-310 K has been defined but lower molecular weight components cannot be excluded. The major component has been cloned, and sequence analysis indicated a complicated pattern of repeating sequences in the C-terminal third of the molecule. This review deals mainly with the effects of toxin A on cultured cells. Most mammalian cells are sensitive to toxin A whose major effect is to stop cell division irreversibly. The toxin binds via its repeat sequences to a trisaccharide receptor expressed on rabbit red cells and on brush border membranes from hamster intestine. This receptor seems to be functional in the hemagglutination reaction and the enterotoxicity. Its role in the cytotoxic effect of the toxin is not clear, but no other receptor structure has as yet been identified. In order to exert its cytotoxic (antiproliferative) effect toxin A must first be internalized by endocytosis. Thus a latency period of at least 30 min after toxin binding to cells is consistently observed, and all cytotoxic effects can be prevented by blocking the endocytosis pathway. The first microscopically visible signs of cytotoxicity consist in retraction and rounding of intoxicated cells. In addition the nucleus becomes polarized to one side of the cell while other cell organelles are not significantly affected. These morphological changes seem to be the consequence of a cytoskeletal rearrangement, mainly involving some components of the microfilament system. Inhibition of macromolecular syntheses as well as permeabilization of the plasma membrane may follow the early cytoskeletal effects and finally lead to cell death. Attempts to identify metabolic pathways of significance in the cytotoxicity suggest that the cytosolic level of Ca2+ is not important, thus excluding certain mechanisms for cell killing. In this respect the cytotoxic mode of action of toxin A clearly differs from that of toxin B. However, the biochemical basis for the antiproliferative effect of toxin A remains unknown. PMID- 1926160 TI - Morphometric studies on venom secretory cells from Bothrops jararacussu (Jararacucu) before and after venom extraction. AB - A comparative morphometrical analysis was carried out on secretory cells from Bothrops jararacussu venom glands, before manual extraction of the venom (milking) and 4 and 8 days after milking. At the 8th day after milking, the cytoplasmic volume increased by 160%. The rough endoplasmic reticulum (RER) volume density increase, up to the 8th day after milking, is mainly due to widening of the intra-scisternal space. The total volume and membrane surface of the RER. Golgi apparatus and subcomponents, secretory vesicles and mitochondria, increased during the experimental period while the volume and surface densities of these organelles, with the exception of the RER, did not vary. The numerical density of Golgi-associated microvesicles per Golgi volume unit also increased. The greatest relative increments in these parameters occurred within the first 4 days. These results are compatible with an increased rate of membrane synthesis and transport in the milked glands and suggest that the membrane biogenesis, degradation and circulation that takes place in the first week after milking is achieved through coordinated cellular mechanisms that maintain the rate between total membrane surface and total cytoplasmic volume unaltered. PMID- 1926161 TI - Protection against tetrodotoxin and saxitoxin intoxication by a cross-protective rabbit anti-tetrodotoxin antiserum. AB - A tetrodotoxin-formaldehyde-keyhole limpet hemocyanin conjugate was used to immunize a rabbit for the production of anti-toxin antiserum. The antiserum cross reacted against both tetrodotoxin (TTX) and saxitoxin (STX), and in a quantitative in vitro assay was able to protect cells in a dose-dependent manner from the effects of either TTX or STX. The antiserum was also able to passively protect mice challenged in vivo with either toxin. Hybridomas producing monoclonal antibodies against toxin were obtained from the spleens of mice immunized with the same conjugate. PMID- 1926162 TI - Uptake and subcellular localization of tritiated dihydro-microcystin-LR in rat liver. AB - Microcystin-LR (MC-LR), a cyclic heptapeptide hepatotoxin (mol. wt = 994) produced by the blue-green alga (cyanobacterium), Microcystis aeruginosa, was reduced with tritium labeled sodium borohydride, converted to [3H]-dihydro microcystin-LR ( [3H]-2HMC-LR), and purified to greater than 99% purity by C-18 reverse-phase high-performance liquid chromatography. The uptake and subcellular distribution of [3H]-2HMC-LR were determined in suspensions of hepatocytes at 0 degrees C and 37 degrees C, or following rifampicin pretreatment, and in perfused rat liver. The remaining cells were homogenized and subfractionated using sucrose gradient centrifugation. Suspensions of 7.5 x 10(6) hepatocytes also were incubated with 10 micrograms/ml of toxin, solubilized in Triton X-100, and ultracentrifuged to pellet the detergent insoluble fraction (containing actin). Isolated rat livers were perfused with media containing [3H]-2HMC-LR and the uptake of radiolabel was determined. Sequential biopsy samples were collected for histologic examination. The remaining liver was homogenized and subcellular fractions prepared. Uptake of radiolabel was rapid in both cell suspension at 37 degrees C and perfused liver; however, uptake in cell suspensions was reduced by about 50% at 0 degrees C and by rifampicin (50 micrograms/ml) pretreatment. Hepatocyte necrosis was observed in isolated perfused livers 45 min after initiation of perfusion with [3H]-2HMC-LR. In both hepatocyte suspensions and perfused livers 65 to 77% of the radiolabel was in the cytosolic fraction. In the hepatocyte suspensions, 13 to 18% of the radiolabel was present in the plasma membrane/nuclear fraction with lesser amounts in the other fractions. Trichloroacetic acid treatment of cytosolic fractions indicated that in hepatocyte suspensions, 50-60% of the radiolabel was bound to cytosolic protein. Studies using the perfused liver confirmed that the majority of the radiolabeled MCLR (78-88%) was bound to cytosolic protein. These data suggest that the uptake of [3H]-2HMC-LR occurs primarily by an energy-dependent transport process involving the rifampicin-sensitive hepatic bile acid carrier and that once inside the hepatocyte, the toxin binds to a cytosolic protein(s). PMID- 1926163 TI - Protection of monkeys against the lethal effects of male funnel-web spider (Atrax robustus) venom by immunization with a toxoid. AB - A stable toxoid was prepared from robustoxin (the lethal polypeptide neurotoxin in the venom of the male funnel-web spider, Atrax robustus) by polymerization with glutaraldehyde. This material was non-toxic in new-born mice. Administration of the toxoid to three Macaca fascicularis monkeys (50-80 micrograms/kg s.c. at 14-day intervals for 8-12 weeks) produced no toxic effects; anti-robustoxin antibodies were detected in serum samples by immunodiffusion tests within 13-27 days. In vivo evidence of successful protection with the toxoid was obtained by challenging the monkeys with male A. robustus venom (50 micrograms/kg i.v.) under anaesthesia with pentobarbitone (one monkey), or with ketamine, halothane and nitrous oxide, 1-26 weeks after the last injection of the toxoid. Only minor respiratory, cardiovascular and skeletal motor disturbances were produced, and all monkeys recovered fully and uneventfully. Challenge with the same dose of venom in non-immunized or robustoxin N-terminal decapeptide ovalbumin conjugate treated monkeys resulted in typical lethal neurotoxic effects, culminating in severe hypotension or death from circulatory and respiratory failure within 280 min. PMID- 1926164 TI - Effect of drugs on the lethality in mice of the venoms and neurotoxins from sundry snakes. AB - I investigated the efficacy of 10 drugs with respect to reducing the lethality in mice of the following venoms and their respective neurotoxins: Bungarus caeruleus venom; Bungarus multicinctus venom, alpha-bungarotoxin, beta-bungarotoxin; Crotalus durissus terrificus venom, crotoxin: Notechis scutatus scutatus venom; Oxyuranus scutellatus venom, taipoxin. The drugs diltiazem, nicergoline, primaquine, verapamil and vesamicol protected mice from the lethality of B. caeruleus venom, B. multicinctus venom, and/or beta-bungarotoxin. Dexamethasone provided protection from B. multicinctus venom, beta-bungarotoxin, crotoxin, O. scutellatus venom and taipoxin. Protective activity resided in amphiphilic drugs and correlated with the charge on the drug at physiological pH. Protection from lethality was maximal when the drugs were administered immediately after injection of the venom or toxin. Nifedipine, piracetam and reserpine provided no protection from any of the venoms or toxins tested. PMID- 1926165 TI - Light and electron microscopic studies of pathologic changes induced in mice by ciguatoxin poisoning. AB - Acute poisoning induced by ciguatoxin or ciguatoxin-4c in male ICR mice was examined by light and electron microscopy. Target organs were the heart, medulla of adrenal glands, autonomic nerves and penis. There were no significant differences between the toxicity of ciguatoxin and ciguatoxin-4c. Either i.p. injection or oral administration (0.7 micrograms/kg) resulted in marked swelling and focal necrosis of cardiac muscle cells and effusion into the interstitial space of the heart. Degeneration of cells in the medulla of the adrenal glands was also observed. Continuous erection of the penis was observed in about 15% of the mice suffering from ciguatoxicosis. Although severe diarrhea was brought about by the administration of these phycotoxins, no morphological alterations were seen in the mucosa and muscle layers of the small intestine except in autonomic nerve fibers and synapses. Atropine suppressed the symptoms of diarrhea but had no effect on the injury to the cardiac muscle. Reserpine aggravated the clinical signs and pathological findings. Guanethidine and 5-hydroxy dopamine as well as those undergoing bilateral adrenalectomy had no significant effects on the ciguatoxicosis. PMID- 1926166 TI - Characterization of cationic binding sites of neurotoxins from venom of the scorpion (Centruroides sculpturatus Ewing) using lanthanides as binding probes. AB - Binding sites for cations were probed in the structures of protein neurotoxins from Centruroides sculpturatus by enhancement of terbium(III) fluorescence, detected by emission at 552 nm, when aromatic side-chains of the toxins were activated at 286 nm. Gadolinium, Gd(III), was used as a cation binding probe by observing its effects on nuclear magnetic resonance (NMR) spectra. Toxins CsE-v2 and v3, when bound to Tb(III), enhance luminescence of Tb(III) 20-fold whereas CsE-v1 enhances Tb(III) luminescence about 15-fold. Toxins CsE-I and V have no effect on the luminescence of Tb(III) implying that these latter two toxins have structures incompatible with efficient energy transfer from activated aromatic side-chains. Enhancement of fluorescence is pH dependent and is competitively inhibited by alkaline earth divalent cations and by other lanthanide(III) ions. Neodymium, Nd(III), with an ionic radius of 0.995 A is the most efficient of the lanthanide ions and the divalent cations in displacement of Tb(III) from the toxins. Relaxation enhancements of aromatic CH resonances by Gd(III) are apparent with tyrosines 4, 42, 38, 14-40 peak and tryptophan 47. Results from pH vs fluorescence studies suggest that carboxyl groups are involved in binding of Tb(III). Association constants (Ka) of the Tb(III)-CsE-v2 and v3 complexes are respectively 2.5 x 10(3) and 2.4 x 10(3) M-1 determined by fluorescence enhancement and 2.4 x 10(3) and 2.3 x 10(3) M-1 by equilibrium dialysis. Similarly Ka values for toxins CsE I and V are respectively 1.9 x 10(3) and 1.8 x 10(3) M-1 determined by equilibrium dialysis. Experimental evidence suggests that at least two Tb(III)s are bound per toxin molecule. The results from these studies are discussed in relation to the tertiary structure of toxin CsE-v3. PMID- 1926167 TI - Further characterization of toxins T1IV (TsTX-III) and T2IV from Tityus serrulatus scorpion venom. AB - Toxins T1IV (TsTX-III) and T2IV have been purified to homogeneity from Tityus serrulatus scorpion venom and further characterized. Their amino acid composition and SDS-PAGE reveal an approximate mol. wt of 7000. Their intracisternal LD50 (micrograms/kg) in mice were 12.9 +/- 1.6 and 3.0 +/- 0.5, while their N-terminal amino acid sequences were K-E-G-Y-A-M-D-H-E-G-C-K-F-S- and K-E-G-Y-L-M-D-H-E-G-C K-L-S-C-F-I-R-P-S-G-Y-C-G-R-E-, respectively. This sequence of T2IV, its amino acid composition and its chromatographic and electrophoretic behaviour identify it as toxin gamma (TsTX-I), which is the major toxin from this venom. TsTX-III (13 to 102 micrograms/kg) produced a long lasting enhancement of the hypertensive effect of noradrenaline and a slight decrease of the hypotensive effect of acetylcholine, while T2IV (115 micrograms/kg) induced a prolonged hypotensive effect on the anesthetized rat. On the isolated guinea-pig vas deferens, TsTX-III (2.1 and 3.0 micrograms/ml) produced a horizontal shift of the dose-response curve for noradrenaline to the left with no change of the maximal response. At a concentration of 1.43 microM, it induced a prolongation of the duration of the B component of the compound action potential. This prolongation was strongly reduced after addition of tetrodotoxin. PMID- 1926168 TI - Purification of a proteinase inhibitor from the plasma of Bothrops jararaca (jararaca). AB - A proteinase inhibitor was isolated from the plasma of Bothrops jararaca by three chromatographic steps: DEAE Sephacel, Phenyl Sepharose and Bio Gel P200. It inhibited caseinolytic and hemorrhagic activity of the whole venom of B. jararaca. Proteolytic activity of bothropasin and J protease, both metalloproteinases of the venom, were neutralized by the inhibitor. The J protease-inhibitor complex was isolated by gel filtration chromatography in HPLC and the electrophoresis pattern of this complex showed that the interaction between enzyme and inhibitor is not covalent. PMID- 1926169 TI - Immunological properties of the fibrinolytic enzyme (fibrolase) from southern copperhead (Agkistrodon contortrix contortrix) venom and its purification by immunoaffinity chromatography. AB - An antibody to the fibrinolytic enzyme in southern copperhead venom was produced by immunizing rabbits with chromatographically purified enzyme. The antibody was purified from rabbit blood by ammonium sulfate fractionation and protein-A affinity chromatography. The purified antibody reacted only with the fibrinolytic enzyme in southern copperhead venom as demonstrated by immunodiffusion and immunoelectrophoresis. Western immunoblotting revealed that several snake venoms, including Agkistrodon piscivorus conanti, Crotalus atrox, Crotalus basiliscus basiliscus, and Bothrops asper, cross-reacted with the antibody to varying degrees. However, Deinagkistrodon acutus showed no cross-reaction. Immobilized antibody has been used, in combination with molecular sieve chromatography, to purify the fibrinolytic enzyme from southern copperhead venom. In this two-step purification procedure, the enzyme was purified in good yield within two days. The specific activity of the enzyme purified by the immunoaffinity chromatography procedure is comparable with that of enzyme purified by a four-step chromatographic procedure. The mol. wt of the purified enzyme is approximately 23,000-24,000 as determined by SDS-PAGE. Interestingly, the enzyme purified by this two-step immunoaffinity chromatography procedure possesses virtually no hemorrhagic activity. PMID- 1926170 TI - Quantitation by enzyme-immunoassay of antibodies against Bothrops myotoxins in four commercially-available antivenoms. AB - An enzyme-immunoassay (EIA) for the quantitation of antibodies against myotoxins present in the venoms of Bothrops asper (Costa Rica), B. atrox (Colombia) and B. moojeni (Brazil), was developed. This EIA was utilized for the evaluation of four antivenoms produced in Mexico (Laboratorios Myn; MYN), Costa Rica (Instituto Clodomiro Picado; ICP), Colombia (Instituto Nacional de Salud; INS) and Brazil (Instituto Butantan; IB). Antivenoms ICP, IB and INS showed a higher titer of antibodies against the three myotoxins tested, with only slight differences between them, depending on the antigen utilized. In contrast, MYN antivenom had very low levels of antibodies to the three myotoxins. Seventeen batches of ICP antivenom were analyzed by EIA, using B. asper myotoxin II as antigen. Although all batches had high anti-myotoxin titers, these varied significantly. Batches produced after 1988 had, in general, higher titers than older (1986-1987) ones. Antivenom stored for one year at 37 degrees C had a slight, but significant (P less than 0.002) decrease of anti-myotoxin activity, compared to antivenom stored at 4 degrees C or 23 degrees C. No correlation was found between anti-myotoxin concentration and lethality-neutralizing ability of the ICP antivenom. PMID- 1926171 TI - Characterization of three hemorrhagic factors from the venom of Okinawa habu (Trimeresurus flavoviridis). AB - Three hemorrhagic factors, HR1, HR2a and HR2b, of Okinawa habu venom were characterized in terms of their subunit structure, amino acid composition, metal content and immunological properties. HR1 is a dimer (mol. wt 90,000) consisting of two identical subunits at 25 degrees C, but polymerizes to form a tetramer at 4 degrees C. Two peaks corresponding to the dimer and the tetramer were observed upon ultracentrifugation analysis at 20 degrees C. HR2a and HR2b are monomers (mol. wt 24,000 and 19,000, respectively). HR1, HR2a and HR2b contain 407, 203 and 161 amino acids, respectively and the respective mol. wt based on the amino acid composition are 45,988, 23,075 and 18,457. The hemorrhagic factors contain Zn2+, Ca2+ and Mg2+, and were irreversibly inhibited by incubation with chelating reagents. The three hemorrhagic factors were immunologically distinguished from each other, and the hemorrhagic activities were inhibited by the respective antiserum. The activity of HR2a was also inhibited by the antiserum against HR2b. PMID- 1926172 TI - Isolation and comparison of myotoxins isolated from venoms of different species of Bothrops snakes. AB - Venoms of nine different snake species of the genus Bothrops were fractionated using fast protein liquid chromatography (FPLC). Basic proteins with phospholipase A2 and/or myotoxic activities were isolated from venoms of B. jararacussu, B. moojeni, B. neuwiedi and B. pradoi. B. jararaca venom possessed very low concentrations of these proteins, which were undetectable in venoms of B. atrox, B. alternatus, B. cotiara and B. erythromelas. Basic proteins from B. moojeni and B. pradoi venoms were isolated in pure form. All active fractions possessed a common band of 15,000 mol. wt which caused a rise in serum creatine phosphokinase levels and histopathological changes in muscle cells following i.m. injection into mice. Levels of phospholipase A2 activity were variable. The implications of the possession of varying levels of myotoxins and phospholipase A2 in these venoms are discussed. PMID- 1926173 TI - Endothelium-dependent relaxant effect of thrombocytin, a serine proteinase from Bothrops atrox snake venom, on isolated pig coronary arteries. AB - Since thrombin causes an endothelium-dependent relaxation of precontracted pig coronary arteries, the ability of thrombocytin, a serine proteinase from the venom of the common lancehead, Bothrops atrox, to induce endothelium-dependent changes in the vascular tone was investigated. Relaxation of pig coronary rings did not appear in vessels denuded of the endothelium. Thrombocytin (0.1-2.0 micrograms/ml) caused an endothelium-dependent, reversible, transient relaxation of PGF2 alpha-precontracted arteries which could be blocked by heparin and relatively high concentrations of alpha-NAPAP, a synthetic competitive thrombin inhibitor. Indomethacin and hirudin did not influence the relaxant effect. Both the thrombocytin- and bradykinin-induced relaxation were diminished by the guanylate cyclase inhibitor methylene blue and by NG-monomethyl-L-arginine. The thrombocytin-induced relaxation was absent in de-endothelialized vessels. Thrombocytin was able to induce aggregation of human blood platelets in Tyrode's solution at the same concentration range as used for the relaxation. Batroxobin neither relaxed precontracted arteries nor aggregated human blood platelets in vitro. The present studies show that the serine proteinase thrombocytin is not only able to aggregate platelets but may also release endothelium-derived relaxing factor from the vascular endothelium. PMID- 1926174 TI - Detection of a cytolytic toxin in the venom of the stonefish (Synanceia trachynis). AB - The venom of the stonefish, Synanceia trachynis, contains a cytolytic toxin which is antigenic and ammonium sulfate-precipitable, and has a pI of ca 5.7 and an Mr of ca 158,000. The toxin is a potent but narrow-spectrum cytolysin which is lytic in vitro for rabbit, dog, rat, and guinea pig erythrocytes, in that order, but is largely or completely inactive against sheep, cow, human, monkey, mouse, goat, horse, burro and cat erythrocytes. Fractionation of the venom by molecular sieve fast protein liquid chromatography and isoelectric focusing did not separate the haemolytic activity from the venom's lethal and vascular permeability-increasing activities. Also, the three activities were destroyed by heat, proteases, Congo red, potassium permanganate and stonefish antivenoms. The results suggest that the haemolytic, lethal and vascular permeability-increasing activities of stonefish venom are properties of the same molecule, a previously unrecognized, membrane-damaging protein toxin. PMID- 1926175 TI - [Toxicity of the molluscicidal plant, Ambrosia maritima L., to aquatic non-target organisms]. AB - The toxicity of the molluscicidal plant, Ambrosia maritima L., has been evaluated in fish, crustacea and algae. The LC50 for fries of the guppy, Lebistes reticulatus, was respectively 650 and 450 mg/litre using a powder or an ether methanol-hexane extract from the leaves of the plant. This concentration is much higher than the molluscicidal concentration (LC90) of 35 to 70 mg/litre, which is used in the field (irrigation canals in Egypt). Preliminary tests showed that juveniles of L. reticulatus and Tilapia aurea were as sensitive as the fries. Using the same extract of A. maritima the LC50 for Daphnia magna was 766 mg/litre and no toxic effects could be observed in algae Selenastrum capricornutum at 1 g/litre. It can be concluded that A. maritima has a very low toxicity to aquatic non-target organisms. It is not toxic when used at the molluscicidal concentration of 35 to 70 mg/litre. PMID- 1926176 TI - Pathodynamics of intoxication in rats and mice by enterotoxin of Clostridium perfringens type A. AB - The pathodynamics of lethal intoxication in rats and mice by i.v. administration of enterotoxin of Clostridium perfringens type A was studied using whole animals and isolated organs. A lethal i.v. dose (50 micrograms/kg) of enterotoxin killed anesthetized rats and mice within 4-15 min. Rapid changes of ECG pattern suggestive of hyperpotassemia, rapid fall of blood pressure and transient hyperpnea followed by respiratory depression were observed. Analysis of plasma levels of cations revealed hyperpotassemia in both animal species. On the other hand, enterotoxin (up to 100 micrograms) showed little direct cardiotoxicity on the isolated heart. ECG changes produced by i.v. injection of KCl (0.5 ml of 50 mM) mimicked the ECG changes observed in the intoxicated rats injected with a lethal dose of enterotoxin. Perfusion of rat isolated organs showed that potassium concentration in the eluent from the liver (but not lungs or lower extremities) increased markedly within 1-2 min after the administration of enterotoxin. The amount of potassium liberated from a rat liver was about 133 mumoles, which is sufficient to increase the plasma level of potassium to more than 10 mM. In addition to potassium, cytoplasmic enzymes, such as glutamate oxalacetate transaminase, glutamate pyruvate transaminase and lactate dehydrogenase, were also liberated from the intoxicated liver, indicating that potassium was liberated from hepatocytes by the change in membrane permeability produced by enterotoxin. It is concluded that hyperpotassemia elicited by the cytotoxic action of enterotoxin on hepatocytes caused cardiac failure leading to the death of the intoxicated animals. PMID- 1926177 TI - Strain dependent production of ciguatoxin precursors (gambiertoxins) by Gambierdiscus toxicus (Dinophyceae) in culture. AB - Thirteen strains of Gambierdiscus toxicus isolated from Queensland (Australia), Hawaii, French Polynesia and the Virgin Islands were mass cultured and extracted for ciguatoxin. A biodetrital sample containing wild G. toxicus collected from the Republic of Kiribati was also extracted for ciguatoxin. Ciguatoxin, as characterized from moray eels, was not detected in any of the strains examined. Two Queensland strains and the wild G. toxicus produced putative ciguatoxin precursors named gambiertoxins. These gambiertoxins were less polar than ciguatoxin but produced bioassay signs in mice and in-vitro responses in isolated guinea pig atria and vas deferens which were similar (but not identical) to those produced by ciguatoxin. The gambiertoxins from cultured cells were also shown to competitively inhibit the binding of [3H]brevetoxin-3 to rat brain membranes in a dose-dependent manner. The gambiertoxins were more potent than ciguatoxin (on a per mouse unit basis) at stimulating neural elements of guinea pig atria. The two culture strains produced similar amounts of gambiertoxins, even when grown in nutrient media made from different seawater containing different concentrations of nutrients. Changes in nutrient media did not induce the other strains of G. toxicus to produce gambiertoxins. The production of these ciguatoxin precursors appears to be limited to only certain genetic strains of G. toxicus, with the majority of strains not producing these toxins. We propose that ciguatera occurs when blooms of G. toxicus strains genetically capable of producing these ciguatoxin precursors enter the marine food chain. These toxins could then become oxidatively metabolized in fishes to the major polar ciguatoxin. Wild cells produced approximately 100-fold greater quantities of gambiertoxins per cell than did the two culture strains indicating that there is considerable potential for increased production of these ciguatoxin precursors from G. toxicus in culture. PMID- 1926178 TI - Neutralization of kinin-releasing enzymes of crotalid venoms by monospecific and polyspecific antivenoms. AB - The amounts of kinin-releasing enzymes in the venoms of Crotalus atrox, Crotalus adamanteus, Crotalus scutulatus scutulatus and Agkistrodon piscivorus piscivorus were measured by determining the amounts of kinin released from a sheep kininogen substrate by means of a specific radioimmunoassay. Four monospecific and two commercial polyspecific antivenom IgG samples were tested for their ability to reduce the kinin-releasing activities of the four crotalid venoms measured in vitro. All of the antivenom IgG samples were able to neutralize venom kininogenase activity to varying extents. On of the commercial polyspecific antivenoms was of equal or higher potency than the corresponding monospecific antivenoms for three of the venoms tested, indicating a high degree of cross neutralization. F(ab')2 and especially Fab fragments of that polyspecific antivenom IgG were also effective in reducing the kinin-releasing activities of the four crotalid venoms. PMID- 1926179 TI - Susceptibility of different strains of mice to South American rattlesnake (Crotalus durissus terrificus) venom: correlation between lethal effect and creatine kinase release. AB - In the present work we report that susceptibility to Crotalus durissus terrificus venom: varies according to the strain of inbred mouse used. The s.c. LD50 for Balb/c and C57BI/6 mice were 193 micrograms/kg and 171 micrograms/kg, whereas for A/J and DBA/J they were 78 micrograms/kg and 74 micrograms/kg, respectively. In addition, a direct correlation between susceptibility to C. d. terrificus venom and creatine kinase serum levels (CK) was observed. PMID- 1926180 TI - Zone-specific hepatotoxicity of gossypol in perfused rat liver. AB - Gossypol selectively damages the periportal region of lobules in perfused rat liver, while retrograde perfusion caused pericentral liver damage. Moreover, the addition of 0.4% bovine serum albumin(BSA) to the perfusate completely prevented the toxic effect of gossypol on hepatocytes, decreasing the absorption of gossypol by the liver. This study indicates that the damage caused by gossypol depends upon the direction of exposure and can be protected against by its binding to BSA. PMID- 1926181 TI - Plant and microbial toxic proteins as hemilectins: emphasis on canatoxin. AB - Ribosome-inactivating plant toxic proteins and ADP-ribosylating microbial toxins share a common structural organization. These proteins present domains displaying different biological properties: a target cell membrane-binding component (B subunit or haptomer) and an enzymatically active component (A-subunit or effectomer). Interactions of these toxins with the target cells are mediated by the hemilectin-like haptomer, which recognizes and specifically binds to a given glycoderivative present at the cell surface. After binding the holoprotein is internalized via endocytosis. Inside the endocytic compartment the toxin is processed to release its effectomer moiety which catalytically modifies a cytoplasmic component, and this step accounts for its toxic effect. The structural relationships between toxic hemilectins and plant lectins are discussed, with emphasis on the example of canatoxin and concanavalin A, both present in the seeds of the jack bean Canavalia ensiformis. Contrary to other plant toxic proteins, which inhibit protein synthesis, canatoxin-induced toxicity includes central nervous system-mediated effects. In vivo as well as in vitro canatoxin acts as lipoxygenase-mediated secretagogue in several types of cells: blood platelets, mast cells, pancreatic islets and synaptosomes. Elucidation of structure vs biological activity relationships of canatoxin and other toxic proteins may provide data for their utilization as pharmacological tools and as therapeutic agents. PMID- 1926182 TI - Purification and characterization of a fibrinogenase from Vipera lebetina (desert adder) venom. AB - A fibrinogenase from Vipera lebetina venom was isolated by gel filtration in a Superose 12 column prep grade HR 16/50 and by ion-exchange in a Mono Q HR 5/5 column. The purified enzyme, which was obtained with a yield of 8 mg from 60 mg of crude venom, is a glycoprotein having an isoelectric point of 5.9 +/- 0.1 and a mol. wt of 26,000 +/- 1000 as estimated by SDS-PAGE. The biochemical characterization of the enzyme revealed that it hydrolyzes readily the B beta chain of fibrinogen and the A alpha chain as well as fibrin and casein. Over a pH range from 4 to 11 the enzyme was not inactivated by a 20 min treatment at 90 degrees C. The isolated fibrinogenase is inhibited by ethylenediamine tetraacetic acid, dithiothreitol and L-cysteine but not by phenylmethylsulfonyl fluoride. On the other hand, it is activated by Ca2+ and Mg2+. Purified fibrinogenase up to a dose of 100 micrograms/mouse shows no toxicity and has no hemorrhagic activity. PMID- 1926183 TI - Tryptophan 65 is essential for hemolytic activity of the thermostable direct hemolysin from Vibrio parahaemolyticus. AB - The effect of modification of aromatic and ionizable amino acid residues on the hemolytic activity of a thermostable direct hemolysin from Vibrio parahaemolyticus was examined. Tryptophan 65, one of the two tryptophan residues per subunit, was specifically modified with N-bromosuccinimide, resulting in complete loss of hemolytic activity. However, neither nitration with tetranitromethane of one of the nine tyrosine residues nor Nlm-ethoxyformylation of two of the four histidine residues caused any change in hemolytic activity. The hemolysin was fully active upon amidation of two reactive carboxyl group. On the other hand, acetylation of amino groups and the modification of one of the three arginine residues with 1,2-cyclohexanedione resulted in a partial loss of the hemolytic activity. The results suggest that Trp65 is essential for the hemolytic activity of V. parahaemolyticus hemolysin. PMID- 1926184 TI - Tetrodonic acid-like substance; a possible precursor of tetrodotoxin. AB - A tetrodonic acid-like substance which was hardly distinguishable from authentic tetrodonic acid in thin-layer chromatography, high performance liquid chromatography, etc., was successfully purified from the ribbon worm and flatworm by a method consisting mainly of Bio-Gel P-2 column chromatography. The tetrodonic acid-like substance showed a specific toxicity of approximately 700 mouse units/mg as tetrodotoxin, unlike tetrodonic acid which is a completely non toxic substance. Instrumental analyses including gas chromatography-mass spectrometry, secondary ion mass spectrometry and thin-layer chromatography/fast atom bombardment mass spectrometry disclosed that the tetrodonic acid-like substance had a structure similar to, but not the same as, that of tetrodotoxin. This, along with its high convertibility into tetrodotoxin during storage and other experimental operations, suggested that the tetrodonic acid-like substance is a precursor of tetrodotoxin. PMID- 1926185 TI - Ontogeny of striking, prey-handling and envenomation behavior of prairie rattlesnakes (Crotalus v. viridis). AB - The ontogeny of striking, prey-handling and envenomation behavior was studied in the prairie rattlesnake (Crotalus v. viridis). Snakes of three size classes (small, medium, large) were allowed to strike and envenomate deer mice (Peromyscus maniculatus) of corresponding size. The mass of venom expended in a single strike, assayed by enzyme-linked immunosorbent assay (ELISA) of whole mouse homogenates, increased exponentially with length of the snake. Small snakes embedded their fangs in prey for a longer duration than larger snakes. Mice were always struck and released, regardless of snake or prey size. Latency to immobilization was similar for mice envenomated by medium and large snakes; small mice struck by small snakes were not mobile. Latency to death and death rate (latency to death divided by mass of mouse) were greater for mice envenomated by small snakes as compared to medium and large snakes. These findings further clarify the ontogenetic and functional relationships between venom, morphology, diet and behavior. They also illustrate how behavior may be modified to maximize envenomation and feeding success. PMID- 1926186 TI - A comparative biochemical, pharmacological and immunological study of Clostridium novyi alpha-toxin, C. difficile toxin B and C. sordellii lethal toxin. AB - The three clostridial cytotoxins, i.e. alpha-toxin of C. novyi (Tox alpha-nov), toxin B of C. difficile (ToxB-dif) and lethal toxin of C. sordellii (LT-sor) consist of single peptide chains of about 200,000 (Tox alpha-nov), 250,000 (LT sor) and 275,000 (ToxB-dif) mol. wts. ToxB-dif and LT-sor but not Tox alpha-nov cross-reacted with rabbit polyclonal antibodies. Toxicity upon i.v. injection in mice was similar (LD50, 100 hr, 50-200 ng/kg) and was characterized by a slowly developing fluid loss into the interstitial space. When injected into the rat paw the toxins caused a delayed local edema lasting for days. In vitro the three toxins provoked a persistent retraction of endothelial cells cultured from pig pulmonary artery. ToxB-dif and Tox alpha-nov triggered the accumulation of F actin in the perinuclear region at the expense of the tight peripheral bands whereas LT-sor led to a random loss of microfilament structure. The toxins inhibited uridine incorporation into endothelial or chicken embryonic cells whereas T 84 cells responded by an about 10-fold increase of uridine incorporation. Neither toxin ADP-ribosylated actin. The similarities between the three cytotoxins warrant their arrangement into a common group which perturbs the microfilament system. PMID- 1926187 TI - Toxicity of adductor muscles from the purple hinge rock scallop (Crassadoma gigantea) along the Pacific coast of North America. AB - Mouse bioassay results of rock scallops occasionally monitored by official agencies of British Columbia, Washington and California before and/or after algal blooms from 1980-1990 revealed that 24%, 38% and 87% of adductor muscles, whole body and viscera, respectively, were unsafe (greater than or equal to 80 micrograms saxitoxin equivalents/100 g tissue) for human consumption. The safety of adductor muscles could not be predicted from corresponding toxicity levels of the viscera but the absence of detectable toxin could. PMID- 1926188 TI - Toxicity of the freshwater puffer fish Tetraodon fangi and T. palembangensis from Thailand. AB - Toxicity of the freshwater puffer Tetraodon fangi and T. palembangensis from Amphur Chumpuang, Nakorn Ratchasima Province, Thailand (where food poisoning due to T. fangi recently occurred) was monitored from December 1988 through October 1989. The puffer were toxic throughout most of the year. There was marked variation in amounts of toxins among individuals and with the time of collection. The highest toxicity levels for T. fangi were found in skin (813 mouse units per g) following by eggs (336), muscle (331), liver (209) and intestine (159). Corresponding values for T. palembangensis were 907, 332, 282, 225 and 143 mouse units/g, respectively. PMID- 1926189 TI - Chymotrypsin treatment increases the activity of Clostridium perfringens enterotoxin. AB - Chymotrypsin treatment of the enterotoxin from Clostridium perfringens results in the loss of 36 amino acids from the N-terminus and 3 amino acids from the C terminus. This processing results in a 3.2 fold increase in activity on Vero cells, which is close to what had been found for trypsin treatment following the loss of 25 amino acids from the N-terminus. PMID- 1926190 TI - Computer modelling of the 3-dimensional structures of the cyanobacterial hepatotoxins microcystin-LR and nodularin. AB - The 3-dimensional structures of two cyanobacterial hepatotoxins microcystin-LR, a cyclic heptapeptide and nodularin, a cyclic pentapeptide, and the novel amino acid ADDA (3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid) were constructed, and optimized using the CHEM-X molecular mechanics program. The peptide rings were planar and of rectangular shape. Optimized ADDA formed a U shape and a difference in the orientation of ADDA with respect to the peptide ring of the two hepatotoxins was observed. PMID- 1926191 TI - Accuracy of a replication technique for biostereometric evaluation of clinical tooth wear. AB - The accuracy of a replication system for biostereometric analysis of denture tooth wear was examined. The differences observed were less than 0.32 per cent which serves to illustrate the degree of accuracy of this technique. PMID- 1926192 TI - Denture requirements of indigents in the Western Cape region. AB - This study was undertaken to determine the denture requirements of indigents who make application to the Department of National Health and Population Development for prostheses. An analysis of 4573 denture application forms for the period 1 January 1983 to 31 December 1984 was undertaken in the Western Cape region in order to obtain the relevant information. The general profile of applicants was that of a middle-aged coloured female who was unemployed with a monthly income of R144.51. Almost 60 per cent of applicants had been edentulous for a period of 1 10 years and the greatest demand was for full upper and lower dentures. The mean period of wearning dentures ranged between 15.9 and 21.7 years. A disturbing finding was that a high percentage of applicants (48.6%) had no motivational reasons for wanting dentures. PMID- 1926193 TI - Dental X-rays-a patient's guide. PMID- 1926194 TI - [The effect of a low-intensity helium-neon laser on succinate dehydrogenase activity in unmineralized periodontal and dental tissues]. AB - Laser effects with energy density of 28.8, 86.4, 144 J/cm2 and 86.4 J/cm2 in combination with fluorine agents on succinate dehydrogenase (SDH) activity were studied in 264 noninbred white rats (5 groups). The animals were decapitated in 1, 6, 12, 24, 48, 72 h and 12 and 30 days. The findings evidence elevated SDH activity virtually in all periods tested. Laser exposure enhanced enzymic activity in all the animals. PMID- 1926196 TI - [The comparative characteristics of treating herpes virus diseases of the oral mucosa with antiviral preparations]. AB - The efficacy of human leukocytic interferon (ointment), 20000 IU/g, in the treatment of viral diseases of the buccal mucosa was studied in 152 patients. The results were compared with those achieved with the commercial antiviral agent 0.5% oxolin ointment. The results evidence a manifest antiviral effect of the interferon ointment, recommending it for practical dentistry. PMID- 1926195 TI - [The effect of a high-saccharose diet on the enzymatic activity of the oral mucosa in rats]. AB - Cathepsin D, acid phosphatase, beta-galactosidase, N-acetyl hexosaminidase, leucine aminopeptidase (LAP), lactate dehydrogenase, glucose-6-phosphate dehydrogenase (g-6-PDH), and peroxidase activities were measured in the buccal mucosa of rats kept for 60 days on high-sucrose (68% of sucrose) caries-inducing diet. The findings evidence that this diet observed for 30 days results in a significant elevation of beta-galactosidase and LAP activities and in reduction of peroxidase level. After 60-day diet the examined parameters virtually did not differ from the reference characteristics (a control group kept on 68% starch diet), except elevated g-6-PDH and lowered peroxidase activities. Enzymic activity changes are adaptive and evidence changes in the metabolic processes in the buccal mucosa, that may eventuate in the development of periodontal diseases. PMID- 1926197 TI - [The use of calcitrin in the combined treatment of periodontitis]. AB - The authors compare the results of calcitrin therapy and surgical (flap surgery) treatment of periodontitis patients. Calcitrin was injected i. m. in a dose of 1.5 to 2 U daily for 14 days. Clinical, laboratory, and functional studies have demonstrated the efficacy of calcitrin therapy in combination with surgical treatment of periodontitis. PMID- 1926198 TI - [Natural body reactivity, the leukocyte intoxication index and salivary alkaline phosphatase in the early diagnosis of inflammatory complications of mandibular fractures]. AB - Analysis of the intoxication leukocytic index (ILI) has shown more manifest changes in the blood obtained by skin puncture at the site of mandibular fracture projection than in the blood from the finger. Total leukocyte count was less changed. The most marked elevation of the regional ILI and alkaline phosphatase (AP) activity in mixed salivary pool were detected in the patients with mandibular fractures complicated by inflammations, irrespective of the time of measurements. These parameters were less elevated in the patients without inflammations starting from the second day after the fracture and still less elevated in those without inflammations within the first 24 hrs after the fracture. A drastic increase of the regional ILI and mixed salivary AP activity may be considered as an early diagnostic criterion of an inflammatory complication associated with a mandibular fracture. PMID- 1926199 TI - [The use of the polymeric sorbent Regenkur in the combined treatment of suppurative diseases of the soft tissues of the face and neck]. AB - Application of regencur, a local draining sorbent, to phlegmons of the face and neck in 48 patients resulted in shortening of the first phase of the wound process, this permitting earlier suturing of the wounds with primary delayed and secondary sutures. Active sorption and local detoxication were conducive to reduction of lipid peroxidation processes in tissues and blood plasma and to enhancement of leukocytic bactericidal activity. PMID- 1926200 TI - [The use of vibrotherapy to prevent suppurative-inflammatory complications in mandibular fractures]. AB - Patients with uni- and bilateral traumatic fractures of the mandible at risk for pyoinflammatory complications were subjected to vibration massage at frequencies identical to those of cardiovascular system. Rheographic evaluation of the blood flow showed vibration-related normalization of the regional circulation at the lesion which went faster and reached the values on the healthy side on day 14. In controls similar improvement took place only in 58% of cases. The results suggest that vibration massage at cardiovascular frequencies can effectively prevent pyoinflammatory complications in the mandible fractures. PMID- 1926201 TI - [The effect of mandibular immobilization in fracture on the function of the salivary glands]. AB - Studies of functional changes in the salivary glands of patients with mandibular fractures treated with intermandibular immobilization have shown that the major factors responsible for these changes were not only the absence of chewing, changed quality and quantity of food, but the duration of immobilization and viscero-visceral reactions of the body as well. PMID- 1926202 TI - [The evaluation of the body hormonal status of patients with phlegmons of the maxillofacial area]. PMID- 1926203 TI - [T- and B-lymphocytes, interleukins and natural killers in patients with osteomyelitis developing after combined injuries to the maxillofacial and craniocerebral areas]. AB - Forty-three patients with traumatic osteomyelitis developing after combined maxillofacial and craniocerebral injuries and thirty normal subjects were examined. Immunologic findings permit distinguishing two groups of patients: those with marked disorders of the T cellular immunity (reduced T helper and Tx counts, interleukin-2 synthesis, and Tx/T suppressor coefficient) and without such shifts. The therapy of patients without manifest immunity shifts was generally effective whereas in those with marked immunity disorders the therapy efficacy was inadequate and the immunity disorders persisted. PMID- 1926204 TI - [Odontogenic anaerobic gas gangrene of the maxillofacial area]. PMID- 1926205 TI - [A comparative evaluation of the efficacy of surgical treatment methods in tumors of the maxillofacial area and neck]. PMID- 1926206 TI - [A morphological basis for the levels of pulp extirpation and root c anal obturation (experimental morphological research)]. AB - Periapical tissue reaction to root canal filling with zinc-eugenol paste (complete or incomplete filling) was studied in 15 teeth of 5 mongrel dogs after total or subtotal pulp extirpation. Inflammatory reaction developed in all the cases. It was more intensive in cases with total extirpation of the pulp followed by complete or incomplete filling of the root canal than after subtotal extirpation of the pulp followed by root canal filling 1-2 mm below the anatomical apical foramen. PMID- 1926207 TI - [The electrocardiographic changes in patients with malignant neoplasms of the maxillofacial area during radio- and chemotherapy]. AB - Electrocardiographic signs of changes in the myocardium were detected in 93.2 percent of 74 patients with malignant maxillofacial tumors; this was due to the presence of coronary disease, myocardial dystrophy, essential hypertension, respiratory abnormalities. The development and progress of these shifts much depended on radiotherapy and chemoradiotherapy of the tumors. The most frequent findings were deviations in the end section of the ventricular complex, reflecting the metabolic and ischemic changes in the myocardium, associated with a rise in radiation and polychemotherapy dosage. Extracoronarogenic myocardial lesions and coronary disease progression were clinically characterized by augmentation of cardiac insufficiency and various arrhythmias with mild pain syndrome. These specific clinical and electrocardiographic features of myocardial involvement should be borne in mind when choosing and carrying out radio- and polychemoradiotherapy of patients with maxillofacial tumors. PMID- 1926208 TI - [Clinical and experimental analysis of the use of the Analgedent electrostimulator for dental analgesia]. AB - Clinical studies and animal experiments have demonstrated an antinociceptive effect of auricular electrostimulation (AE), 15 Hz, 300 microA, 25 min, on toothache. Perceptual and emotional vegetative components of the painful reaction were reduced by AE in 60 percent of patients and 64 percent of animals. Intravenous naloxone (0.2 mg/kg) abolished AE analgetic effect. The absence of AE analgetic effect in 40 percent of patients and 36 percent of animals can be explained by individual features of the endogenic opioid system functioning. Prospects of AE clinical application with various stimulation frequencies are discussed. PMID- 1926209 TI - [The determination of the porosity of a basic acrylic plastic by mercury porometry]. AB - A method for estimation of pore sizes in acrylic plastic dentures is described. Size-distribution of pores may be a very informative characteristic of not only strength, esthetic, and hygienic characteristics of dentures, but an indicator of a plastic polymerization process in various humidity and temperature conditions. PMID- 1926210 TI - [The deformation-strain state of bridgework dentures]. AB - Holographic interferometry was used to study strained deformed status of bridge dentures. The technique of measurements with a small holographic system is described. Dentures made of Cr-Ni steel with a principally new method of crown to intermediate part adhesion were under study, as were other bridge denture designs. The findings evidence that holographic interferometry may be used as a sparing method for checking up the quality of casting and adhesion of abutment crowns and an intermediate part of fixed dentures, as well as the strength of adhesion of the facing material (porcelain, plastic) to the metal base of the denture. PMID- 1926211 TI - [The x-ray cephalometric characteristics of the facial skeleton in mesial occlusion]. AB - Facial skeleton was studied by roentgenocephalometric analysis in 30 patients with mesial occlusion and in 63 with orthognathic occlusion. A multidimensional statistical analysis helped specify the pathogenesis of multidimensional occlusion, resultant, first of all, from discrepancy in the development of the jaws. This factor leads to the formation of the so-called forms of mesial occlusion, clinically the most incident. PMID- 1926212 TI - [A prosthodontic method for patients with partial tooth loss using metal-ceramic dentures]. AB - The authors suggest a method for making cermet dentures that permits improving by 25-30% the adhesion of porcelain to metal carcass. This method was employed in supplying 162 patients with prostheses. A stronger porcelain-metal compound permitted a sparing preparation of abutment teeth and porcelain coating of 20-50% of the prosthesis metal carcass without deteriorating the strength and aesthetic characteristics of the denture. PMID- 1926213 TI - [Changes in autonomic homeostasis during anesthesia induction in patients operated on for congenital cleft palate]. AB - Variation pulsometry was used to study vegetative homeostasis changes over the course of induction anesthesia and tracheal intubation in children operated on for palatal clefts. The same premedication scheme was employed in all the patients. The same neuroleptic doses were administered in induction anesthesia. Induction anesthesia parallel with electroanalgesia with an Electronarcol-1 apparatus helped reduce the promedol dose necessary for adequate anesthesiologic protection from 1.2-1.4. to 0.2-0.4 mg/kg. This was associated with the minimal changes in autonomic nervous system functioning, evidencing the efficacy of electroanalgesia in induction anesthesia for this patient population. PMID- 1926214 TI - [Periapical cyst of the maxillary teeth as a cause of odontogenic maxillary sinusitis]. PMID- 1926215 TI - [The characteristics of the panoramic image of the maxillodental system obtained on orthopantomographs of different designs]. PMID- 1926216 TI - [The principles of managing emotional stress in patients under ambulatory dental consultation]. PMID- 1926217 TI - [The use of elements of the "programming without a programmer" technology for automating graphic information analysis in dentistry]. PMID- 1926218 TI - [The treatment of infected odontogenic jaw defects with demineralized bone allograft]. AB - Reparative osteogenesis of infected mandibular defects with these defects filled with mineral-free allobone, impregnated with a complex antiseptic solution, was studied in 36 rabbits by morphologic methods. Good results of such treatment permitted using this plastic material in 79 patients with cavitary odontogenic mandibular defects. 8-12 months after surgery osseous tissue structure at the site of defect did not differ from the adjacent tissue. Mineral-free bone tissue impregnated with complex antiseptic solution holds good promise in transplantation surgery. PMID- 1926219 TI - [The State Institute of Dentistry in the system of higher odontological education in the USSR (on the 70th anniversary of the N. A. Semashko Moscow Medical Stomatology Institute)]. PMID- 1926221 TI - [The topical olympiad--one of the forms of student independent work]. PMID- 1926220 TI - [The first printed textbook on medicine with a section on tooth diseases in the Russian language]. PMID- 1926222 TI - [Sugar substitutes and the prevention of caries (facts, prospects, shortcomings)]. PMID- 1926223 TI - [Computed and nuclear magnetic resonance tomography in the diagnosis of diseases and injuries of the temporomandibular joint]. PMID- 1926224 TI - [On the 90th anniversary of the birth of E. E. Platonov]. PMID- 1926225 TI - Where the hormones, there moan I. AB - This autobiography traces the effects of "marriages" of different fields on the development of new directions of research. Such events occurred several times in my career and generated much of my research. PMID- 1926226 TI - Synthesis of side-chain homologated analogs of 1,25-dihydroxycholecalciferol and 1,25-dihydroxyergocalciferol. AB - A novel synthesis of side-chain homologated analogs of vitamin D isomers has been described. The synthesis allows for the insertion of the double bond into the C 24 position of the side chain. The key synthetic step involves the coupling of a new C24-vitamin D synthon with the respective side-chain fragment. The method is illustrated by the preparation of (24E)-24,24a-dehydro-24,24-dihomo-1,25 dihydroxycholecalcife rol (1) and (24b R)- and (24b S)-24,24-dihomo-1,25 dihydroxyergocalciferols (2 and 3). Trans geometry of the newly formed double bond in the side chain was confirmed by high field nuclear magnetic resonance spectra. PMID- 1926227 TI - Synthesis and conversion study of a radiolabeled putative ecdysone precursor, 5 beta-cholest-7-ene-3 beta,6 alpha,14 alpha-triol in Locusta migratoria prothoracic glands. AB - In previous studies, we have characterized the last three steps of the biosynthetic pathway of the insect molting hormone, ecdysone. They consist of a series of hydroxylations at the C-25, C-22, and C-2 positions. To explore an early step, we synthesized 5 beta-cholest-7-ene-3 beta,6 alpha,14 alpha-triol in tritiated form. Incubation of this triol with insect prothoracic glands, a well known site of ecdysone biosynthesis, showed that this molecule can be hydroxylated at the C-25, C-22, and C-2 positions, but neither the triol nor the resulting compounds could be oxidized at the C-6 position to give ecdysone. PMID- 1926228 TI - Direct radioimmunoassay of androstenediol-3-sulfate in the serum of normal men. AB - A commercially available antidihydrotestosterone antiserum was used for the direct radioimmunoassay of androstenediol-3-sulfate (ADS) in human serum. Aliquots of 1 or 2 microliter male serum (mean age of 40 subjects, 38.2 +/- 5.0 years) were diluted and extracted with ethanol for assay. The tracer, [7-3H]ADS, was prepared by sodium borohydride reduction of [7-3H]dehydroepiandrosterone sulfate (DS). Significantly cross-reacting steroids were testosterone, DS, androsterone sulfate, and epiandrosterone sulfate, which combined to produce a mean overestimation of ADS of 4.3 micrograms/dl in male serum. Mean serum ADS was 23.6 +/- 10.0 micrograms/dl (SD) in 20 fresh-frozen sera versus 28.4 +/- 9.7 micrograms/dl (SD) in 20 long-term (24.4 +/- 1.2 years) frozen specimens, showing stability on long-term frozen storage. Androstenediol-3-sulfate also showed a strong correlation with serum DS (r = 0.75). The possible physiologic significance of ADS is discussed, particularly in terms of the known estrogenicity of unconjugated androstenediol. PMID- 1926229 TI - Interaction of [3H]nomegestrol acetate with cytosolic progesterone receptors from the rat uterus. AB - The binding characteristics of the progestin 17 alpha-acetoxy-6-methyl-19 [3H]norpregna-4,6-diene-3,20-dione, nomegestrol acetate ([3H]NOM-Ac) to progesterone receptors (PgRs) of uterus were determined in the rat. Scatchard plot analysis of the equilibrium binding data showed that [3H]NOM-Ac binds to uterine PgR with a Kd of 5.44 +/- 1.27 nM and a Bmax of 1.51 +/- 0.11 pmol/mg protein. Analysis of dissociation kinetics showed that [3H]NOM-Ac dissociates slowly from the PgR, k - 1 = 4.9 +/- 0.5 10(-5) s-1. Competition experiments against [3H]NOM-Ac showed the specificity of the binding with a sequence in relative affinity as follows: ORG 2058 greater than P greater than NOM-Ac greater than medroxyprogesterone acetate greater than megestrol acetate greater than cyproterone acetone greater than NOM. PMID- 1926230 TI - Subcellular distribution of 3 beta-hydroxysteroid dehydrogenase-isomerase in bovine and murine adrenocortical tissue: species differences in the localization of activity and immunoreactivity. AB - Key to the production of biologically active steroids is the enzyme 3 beta hydroxysteroid dehydrogenase-isomerase. Some controversy has arisen concerning the subcellular distribution of this enzyme within steroidogenic cells. The distribution of 3 beta-hydroxysteroid dehydrogenase-isomerase was assessed in subcellular fractions obtained from homogenates of rat, bovine, and mouse adrenal glands in two ways. The activity of 3 beta-hydroxysteroid dehydrogenase-isomerase was quantitated by measuring the conversion of radiolabeled pregnenolone to radiolabeled progesterone in an aliquot of each of the fractions obtained. The presence of the enzyme was assessed by performing Western analyses on aliquots of each of the fractions obtained with the use of a specific polyclonal antiserum against 3 beta-hydroxysteroid dehydrogenase-isomerase, the characterization of which is described. In control experiments, the degree of contamination of the fractions was determined by assessing the presence of known subcellular fraction markers with Western analysis. In the bovine and mouse adrenal glands, 3 beta hydroxysteroid dehydrogenase-isomerase appears to be localized solely in the microsomal fraction, while in the rat, 3 beta-hydroxysteroid dehydrogenase isomerase appears to have dual subcellular distribution: the microsomes and the inner mitochondrial membrane. We conclude that there is a species difference in the subcellular distribution of this important steroidogenic enzyme and that this species difference may be related to the steroidogenic pathway preferred in that species. PMID- 1926231 TI - Isolation of five new 5 alpha-hydroxy-6-keto-delta 7 sterols from the marine sponge Oscarella lobularis. AB - Five novel sterols isolated from the marine sponge Oscarella lobularis have been identified on the basis of spectral arguments: cholest-7-ene-3beta,5alpha-diol-6 one (1), cholesta-7,22E-diene-3beta, 5alpha-diol-6-one (2), 24-methylcholesta 7,22E-diene-3beta,5alpha-diol-6-one (3), 24-methylcholesta-7,24(28)-diene 3beta,5alpha-diol-6-one (4), and 24-ethylcholest-7-ene-3beta,5alpha-diol-6-one (5). PMID- 1926232 TI - Carotid surgery versus medical therapy in asymptomatic carotid stenosis. The CASANOVA Study Group. AB - BACKGROUND AND PURPOSE: The CASANOVA study (Carotid Artery Stenosis with Asymptomatic Narrowing: Operation Versus Aspirin) is a multicenter trial in 410 patients with asymptomatic stenosis (50-90%) of the internal carotid artery who were randomized after angiography. METHODS: In group A, 206 patients with unilateral and bilateral stenosis had surgery unilaterally or bilaterally, respectively. In group B, 160 patients with unilateral stenosis had no initial surgery, whereas those with bilateral stenosis had surgery on the more affected side. Patients were operated on during the 3-year follow-up period if one of the following events occurred: development of a stenosis exceeding 90%; development of a bilateral internal carotid artery stenosis greater than 50% (operation on the more affected side); transient ischemic attack in the region supplied by the internal carotid artery, together with a stenosis of this artery greater than 50%; development of an internal carotid stenosis greater than 50% contralateral to the operated side or restenosis greater than 50% in group A. All patients were treated with 330 mg acetylsalicylic acid and 75 mg dipyridamole three times daily. The minimal follow-up was 3 years. End points were ischemic neurologic deficit exceeding 24 hours or death due to surgery or stroke. RESULTS: Altogether, 334 carotid endarterectomies were performed. Complications of angiography and operation (6.9%) were included. Statistical analysis found no significant difference in the number of neurologic deficits and deaths between the two groups. CONCLUSIONS: Carotid endarterectomy for asymptomatic patients with a stenosis of the internal carotid artery of less than 90% is not recommended at this time except as part of a controlled clinical trial. However, cases of higher grade stenosis (greater than 90%) were excluded from this study and were referred for operation. No conclusion can be rendered regarding the potential benefit of endarterectomy in these higher risk categories. PMID- 1926233 TI - Epidemiological characteristics of lacunar infarcts in a population. AB - BACKGROUND AND PURPOSE: This study evaluated the characteristics and natural history of patients with lacunar (small, deep) cerebral infarcts in a defined population for comparison of these characteristics to those in patients with nonlacunar infarcts. METHODS: This is a population-based study in Rochester, Minnesota, from 1960 to 1984, that used the medical record-linkage system to identify and characterize patients with cerebral infarction. RESULTS: The age- and sex-adjusted average annual incidence rate of lacunar cerebral infarction was 13.4/100,000 persons, accounting for 12% of all first cerebral infarcts. Temporal trends in incidence rates, stroke recurrence rates, prevalence of diabetes mellitus, and causes of death (given survival for 30 days) for cases of lacunar infarction were not significantly different from those for cases of nonlacunar infarction. Hypertension was found in 81% of patients who had a lacunar infarct and in 70% of patients who had a nonlacunar infarct (p = 0.05). A potential cardiac source of embolism was found in 12% of patients who had a lacunar infarct and in 28% of patients who had a nonlacunar infarct (p = 0.002). Survival was significantly better after a lacunar infarct than after a nonlacunar infarct. CONCLUSIONS: Small, deep cerebral infarcts had many of the epidemiological characteristics of other cerebral infarcts but there was a slightly higher frequency of hypertension, significantly lower frequency of a cardiac embolic source, and significantly better survival in patients with lacunar infarction than in those with nonlacunar infarction. PMID- 1926234 TI - Computed tomographic-angiographic findings within the first five hours of cerebral infarction. AB - BACKGROUND AND PURPOSE: Modern management of acute stroke necessitates early diagnosis. To this end, we sought to delineate the radiographic features of focal hemispheric infarction within 5 hours of ictus. METHODS: Fifty patients, ages 54 79, with ischemic strokes productive of at least hemiparesis underwent computed tomographic scanning and cerebral angiography (n = 38) or carotid ultrasound (n = 12). Radiographic lesions were characterized for location, size, and pathophysiology. RESULTS: Acute abnormalities, hypodensity, and mass effect were seen in 56% of scans and confirmed on a second scan 5-7 days later. Intracranial angiographic abnormalities occurred in 61% of patients: arterial occlusions in 45% and delayed arterial filling in 16%. Hemorrhagic infarctions occurred in 26% of second scans and were associated with mass effect (100%) and arterial occlusions (89%). Infarcts with hemorrhagic transformation were larger on both scans than those without (p = 0.001). Of four patients with infarctions in watershed territories on the scans, two had middle cerebral artery occlusions on angiography, thereby questioning the specificity of such scan lesions to low-flow states. CONCLUSIONS: We conclude that cerebral infarctions are often visible on early scans, but their locations may not be etiologically determinative. The infarcts associated with intracranial arterial occlusions (45%) were of thromboembolic origin, but, given current controversies as to the pathophysiology of lacunar and watershed infarctions, we cannot ascertain the etiology in the remainder. These findings are relevant to the new stroke therapies that require administration in the first hours after infarction. PMID- 1926235 TI - Determination of S-100 and glial fibrillary acidic protein concentrations in cerebrospinal fluid after brain infarction. AB - BACKGROUND AND PURPOSE: We initiated the present study to evaluate the clinical value of consecutive concentration determinations of S-100 and glial fibrillary acidic proteins in cerebrospinal fluid from patients with brain infarction. METHODS: We took sequential samples of cerebrospinal fluid from 28 patients within 48 hours, at 7 days, and at 18-21 days after the ictus. We measured astroglial protein concentrations using an enzyme-linked immunosorbent assay and also determined size of the infarction (computed tomography), clinical state of the patient (simplified activities of daily living test), blood-brain barrier dysfunction (cerebrospinal fluid/serum albumin ratio), and a myelin marker (myelin basic protein). RESULTS: We found a transient increase of both proteins in the cerebrospinal fluid during the first week after the ischemic stroke (p less than 0.05). This increment was significantly correlated with the size of the infarction and the clinical state of the patients. CONCLUSIONS: Transient release of astroglial proteins into the cerebrospinal fluid possibly reflects initial focal ischemic damage and, in the later phase, ongoing destruction of astroglial cells in the penumbra zone. We suggest that determinations of cerebrospinal fluid astroglial protein concentrations can be used to estimate ischemic brain damage, which should be of particular value in clinical trials of pharmacological agents, such as calcium antagonists, on stroke patients. PMID- 1926236 TI - Effect of indomethacin on edema following single and repetitive cerebral ischemia in the gerbil. AB - BACKGROUND AND PURPOSE: Repetitive periods of cerebral ischemia result in more severe injury than a single period of ischemia of similar total duration. We investigated the possibility of prostaglandin mediation of this increased injury by attempting to modify brain edema formation with indomethacin pretreatment. METHODS: Under halothane/N2O anesthesia, groups of gerbils underwent bilateral carotid occlusion to induce forebrain ischemia. Group I underwent a single 15 minute period of carotid occlusion. Group II underwent three 5-minute periods of occlusion at hourly intervals. Groups III and IV were similar to groups I and II, respectively, but received 0.2 mg/kg indomethacin before carotid occlusion. Cortical and cerebellar water and sodium contents were determined in control animals (n = 6) at time zero and in experimental animals 24, 48, and 72 hours after ischemia (n = 6-10 gerbils/group at each time point). RESULTS: Cortical water and sodium contents in group II peaked 48 hours after insult (82.15 +/- 0.31% and 420 +/- 14 meq/kg dry wt, respectively) and were significantly higher than control and group I values at both 24 and 48 hours. Cortical water did not change from control in group I animals. Indomethacin pretreatment significantly attenuated increases in water and sodium content seen at 48 hours in gerbils undergoing repetitive ischemia (peak 80.02 +/- 0.45% and 300 +/- 39 meq/kg dry wt), but did not affect mortality. CONCLUSIONS: Indomethacin lessens edema after repetitive cerebral ischemia, suggesting that elevations of cyclooxygenase products are responsible, at least in part, for severe brain edema following repetitive ischemia. PMID- 1926237 TI - Protective effect of flunarizine on blood-brain barrier permeability alterations in acutely hypertensive rats. AB - BACKGROUND AND PURPOSE: Increased cerebrovascular permeability to protein is a well-documented finding in acute and chronic hypertension. In this study, we examined the effect of pretreatment with a calcium entry blocker, flunarizine, on the increased cerebrovascular permeability to protein that develops in norepinephrine-induced acute hypertension. METHODS: Protein transfer was assessed qualitatively with Evans blue dye and quantitatively with iodine-125-labeled serum albumin. RESULTS: Brains of hypertensive rats showed increased permeability to both tracers. The number and size of the areas of Evans blue extravasation were smaller in the hypertensive groups pretreated with flunarizine intravenously. This was supported by the quantitative studies, which demonstrated a significant decrease in protein transfer in total brain of hypertensive rats pretreated with intravenous flunarizine, 1 mg/kg (p less than 0.005) and 2.5 mg/kg (p less than 0.001). Data from individual brain regions showed that pretreatment with flunarizine resulted in significant reduction of protein transfer in most brain regions. CONCLUSIONS: These data support the hypothesis that calcium plays a role in increased cerebral endothelial permeability in hypertension. PMID- 1926238 TI - MK-801 does not protect against hypoxic-ischemic brain injury in piglets. AB - BACKGROUND AND PURPOSE: The excitatory amino acid inhibitor MK-801 has been shown in many animals species to protect against hypoxic-ischemic brain injury. We sought to determine whether hypoxic-ischemic injury to the newborn pig's brain could be prevented by the use of MK-801. METHODS: Hypoxic-ischemic injury to the brain was induced in forty 0-3-day-old piglets. They were randomized to receive either 3 mg/kg MK-801 (MK-801 group, n = 20) or vehicle (control group, n = 19) prior to insult. At time 0, the carotid arteries were ligated and the blood pressure was reduced by one third by hemorrhage. At 15 minutes, inspired oxygen was reduced from 50% to 6%. At 30 minutes, inspired oxygen was changed to 100%, carotid ligatures were released, and the withdrawn blood was reinfused. An additional 14 piglets received 3 mg/kg MK-801 but not hypoxic-ischemic injury (drug-only group), and a final group of 11 piglets were subjected to only a sham operation (sham group). RESULTS: Neurological examination scores at 24, 48, and 72 hours showed that MK-801 and drug-only piglets were significantly worse than the controls. Pathological examination of the brains at 72 hours showed significantly greater damage in the brains of the MK-801 and control pigs relative to the sham and drug-only groups. No differences were found between the control and the MK-801 groups. No differences were found between the sham and drug-only groups. CONCLUSIONS: MK-801, at a dose of 3 mg/kg, causes neurological dysfunction in piglets lasting at least 72 hours, but neither causes brain damage nor ameliorates the effects of hypoxic-ischemic injury to the brain of the newborn pig. PMID- 1926239 TI - Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. AB - BACKGROUND AND PURPOSE: Microvascular perfusion defects may accompany sustained occlusion and subsequent reperfusion of the middle cerebral artery; however, the nature of such "no-reflow" defects remains unclear. METHODS: In the absence of antithrombotic pretreatment, we documented lenticulostriatal microvascular flow integrity following 3-hour middle cerebral artery occlusion and 1-hour reperfusion in a baboon occlusion/reperfusion model by two methods identifying 1) microvascular occlusion and 2) microvascular patency. RESULTS: Microvascular "no reflow" involved capillaries (vessels of 4.0-7.5 microns diameter) of the lenticulostriatal territory. Capillary reflow included 27-39% of all capaillaries in two subjects, indicating a significant reduction of perfusion from normal (2p = 0.045). In identical experimental preparations, single polymorphonuclear leukocytes completely occluded 4.7% of microvessels of capillary diameter in randomly selected fields, partially occluded 3.5% of postcapillary venules, and occluded 40% (four of 10) of capillaries in linear reconstruction along a 110 microns length. Circumferential contact between polymorphonuclear leukocytes and the luminal endothelial cell membranes was documented, with an intrecellular gap of, at most, 160 nm. Fibrin was found with degranulated platelets when the latter were associated with granulocytes, but not with polymorphonuclear leukocytes alone. CONCLUSIONS: The finding of capillary-obstructing polymorphonuclear leukocytes in the microvascular bed following middle cerebral artery reperfusion in focal ischemia in this model satisfies an essential requirement for postulating their role in early microvascular injury and the "no-reflow" phenomenon. PMID- 1926240 TI - Evaluation of 99mTc-hexamethylpropyleneamine oxime cerebral blood flow mapping after acute focal ischemia in rats. AB - Although the blood flow tracer hexamethylpropyleneamine oxime is now widely used for cerebral blood flow mapping using single-photon emission computed tomography, its uptake into acutely ischemic brain has not been well studied. We performed a double-label autoradiographic study in which 99mTc-hexamethylpropyleneamine oxime uptake was compared with [14C]iodoantipyrine-derived cerebral blood flow 0.5, 24, and 72 hours after middle cerebral artery occlusion in 11 rats. We noted excellent correspondence between iodoantipyrine and hexamethylpropyleneamine oxime autoradiograms at all times with both simultaneous tracer injection and 30 minute separation of tracer injections. When the ischemic and hyperemic areas were measured from the same brain section using the two different tracers, hexamethylpropyleneamine oxime underestimated the iodoantipyrine-derived areas by less than 1% (95% confidence interval -2.9% to 2.3%). The maximum discrepancy ( 19%) was seen at high flows. When the two tracers were injected separately, the uptake of hexamethylpropyleneamine oxime was not linear compared with iodoantipyrine-derived cerebral blood flow, but the relation became linear after the Lassen correction factor was applied. Hexamethylpropyleneamine oxime uptake thus accurately represents cerebral blood flow 0.5-72 hours after acute cerebral ischemia. PMID- 1926241 TI - Cholinergic deafferentation after focal cerebral infarct in rats. AB - BACKGROUND AND PURPOSE: For a better understanding of neuronal network disturbances after stroke, we investigated the changes in the cholinergic system after experimental focal infarct. METHODS: We quantitatively evaluated the highly sensitive acetylcholinesterase histochemistry and local glucose utilization 7 days after left middle cerebral artery occlusion in Wistar rats. RESULTS: In all rats with occlusion, the ipsilateral frontal cortex and the nucleus basalis Meynert developed no infarct, whereas the subcortical striatum did. In the frontal cortex on the occlusion side, the acetylcholinesterase-positive fiber density was significantly (p less than 0.05) reduced; a computer-assisted image analyzing system quantified approximately 1.0 m/mm3 brain cortex acetylcholinesterase-positive fibers in the ipsilateral frontal cortex layers II IV and approximately 9.7 m/mm3 brain cortex acetylcholinesterase-positive fibers in the contralateral frontal cortex layers II-IV. Local glucose utilization was also significantly (p less than 0.05) decreased in the ipsilateral frontal cortex compared to the contralateral side and sham-operated animals. CONCLUSIONS: These results suggest that functional disturbances and disruption of the cholinergic pathway between the frontal cortex and the nucleus basalis Meynert occur after middle cerebral artery occlusion in rats. PMID- 1926242 TI - Autosomal dominant syndrome with strokelike episodes and leukoencephalopathy. AB - BACKGROUND AND PURPOSE: We conducted a prospective survey of a family presenting a new syndrome characterized mainly by recurrent strokelike episodes and neuroimaging evidence of leukoencephalopathy. SUMMARY OF REPORT: Forty-five members of a single family were studied clinically and with magnetic resonance imaging. Nine had strokelike episodes, including transient ischemic attacks, and minor or major strokes starting between the fourth and sixth decades, with neuroimaging evidence of small, deep infarcts and a widespread white matter disorder. Other symptoms included migraine (three), dementia (two), epilepsy (one), and hearing loss (one). In some patients, we found various immunologic anomalies and muscular lipidosis without ragged-red fibers. Eight other family members were clinically normal, but had identical neuroimaging signs of leukoencephalopathy. No abnormality was detected in the 28 other members of the family examined. Extensive investigations failed to reveal any known cause of cerebral ischemia. CONCLUSIONS: There appears to be a new syndrome in this family that is characterized by recurrent subcortical strokelike episodes, leukoencephalopathy, immunologic anomalies, muscular lipidosis, and an autosomal dominant pattern of transmission. PMID- 1926243 TI - Tolerance of low cerebral intracellular pH in rats during hyperbaric hypercapnia. AB - BACKGROUND AND PURPOSE: Brain acidosis from cerebral ischemia is characterized by average intracellular pH levels of approximately 5.8-6.2, which appear in turn to worsen cellular injury. We report that the brain is not injured when hypercapnia is used to reduce intracellular pH to about 6.2 during adequate oxygenation. A hyperbaric chamber is needed to achieve intracellular pH values so low because inspired CO2 tensions must be increased to approximately 1 atm. SUMMARY OF REPORT: Using in vivo phosphorus-31 and proton nuclear magnetic resonance spectroscopy, we measured brain intracellular pH and lactate concentration of rats inside a nonmagnetic polycarbonate chamber at a barometric pressure of 1,500 mm Hg. Intubated rats were ventilated with a 50% O2/50% CO2 gas mixture for specific times. All six rats ventilated for 15 minutes with CO2 tensions of approximately 750 mm Hg woke up without neurological impairment, despite a decrease in intracellular pH to about 6.2. Higher CO2 tensions and longer exposures resulted in cardiovascular collapse and sudden death, followed by the postmortem appearance of brain lactate. CONCLUSIONS: Brain intracellular pH values near 6.2 can be induced briefly in vivo in ventilated rats without injury under hyperbaric hypercapnic conditions. If attempts are made to lower brain pH in vivo even further by increasing PCO2 beyond 750 mm Hg, mean arterial blood pressure and cerebral blood flow decrease to values incompatible with life. PMID- 1926244 TI - Computed tomographic evaluation of bleeding sites in primary pontine hemorrhages. AB - BACKGROUND: With the aim of identifying common bleeding sites and probable parent vessels in "small" primary pontine hemorrhages, we reviewed computerized tomographic scans of 20 patients with hematomas less than 2.5 cm in diameter. SUMMARY OF REPORT: We used scans depicting the upper and lower pons and plotted the centers of the hematomas, assuming them to be a probable source of bleeding. No predilection sites were found on the axial plane. CONCLUSIONS: Both the paramedian and the long and short circumferential arteries were probable sources of hemorrhage in the present series. PMID- 1926245 TI - Cardioembolic stroke revealed by increased hemostatic markers associated with intracardiac thrombus. AB - BACKGROUND AND PURPOSE: The presence of hemocoagulative disorders in acute ischemic stroke has been reported occasionally. However, the cause of the hemostatic derangement has not been fully elucidated. CASE DESCRIPTION: A 66-year old woman with a history of hypertension and myocardial infarction developed pure motor hemiparesis. On admission, she was thought to have a lacunar infarction. However, computed tomography of the brain with contrast medium revealed a small infarct in the cortex of the frontal lobe. Conventional angiography showed no stenotic or occlusive lesions. Sensitive hemocoagulative tests revealed hypercoagulative and hyperfibrinolytic states. Ultrafast computed tomography of the heart with contrast enhancement demonstrated a large left ventricular mural thrombus. There were no further abnormal findings suggestive of other systemic diseases that affect blood coagulability. As a result, the patient was diagnosed as having suffered a cardioembolic stroke. CONCLUSIONS: An intracardiac thrombus could be one of the causes of the hemostatic disorders of acute cardioembolic stroke. PMID- 1926246 TI - Central nervous system infarction related to cocaine abuse. AB - BACKGROUND: Cocaine use in the United States has reached epidemic proportions, and increased availability of "crack" since 1983 has noticeably increased the incidence of neurovascular complications. In this report, we examine the relationship between cocaine use and ischemic infarct. SUMMARY OF COMMENT: This study reports 18 cases of ischemic cerebrovascular events, which occurred among 15 men and three women aged 21-47 years who were evaluated in a 2-year period. Clinical presentations include thirteen cases with hemispheric infarcts, two brain stem strokes, two anterior spinal artery infarcts, and one with both hemispheric and cerebellar infarcts. Nine patients smoked crack, four snorted cocaine, and three injected it intravenously. In two cases, the route of administration could not be determined. Two patients died, but the other survived with various degrees of neurological deficit. CONCLUSIONS: Traditional risk factors for strokes were identified in only six patients, suggesting that these factors are not necessary for the occurrence of a cocaine-related infarct. Multiple overlapping mechanisms may be responsible, including vasospasm, sudden onset of hypertension, myocardial infarction with cardiac arrhythmias, increased platelet aggregation, and vasculitis. PMID- 1926247 TI - Acetazolamide test evaluating cerebral autoregulation. PMID- 1926248 TI - A glass of water at midnight for possible prevention of cerebral infarction. PMID- 1926249 TI - Sneddon's syndrome with antiphospholipid antibodies and arteriopathy. PMID- 1926250 TI - Traditional Chinese medical theory and human circadian rhythm in the occurrence of ischemic stroke. PMID- 1926251 TI - Total cholesterol as a risk factor in stroke. PMID- 1926252 TI - Nihilism and stroke therapy. PMID- 1926253 TI - A methodological appraisal of research on prognosis after transient ischemic attacks. AB - We analyzed existing research on the prognosis of patients who have had a transient ischemic attack to identify studies that adhere to basic methodological principles and to identify underinvestigated questions. Studies were eligible for analysis if they were published in peer-reviewed journals after 1950, written in English, and included at least 50 patients with transient ischemia. Studies that included patients with stroke were included only if they reported outcome rates separately for the subgroup of patients with transient ischemia. All eligible studies were extracted by one investigator who recorded adherence to six key methodological principles. Among 60 eligible studies, 54 were observational cohort studies and six were randomized trials. Adherence to the six methodological principles was as follows: eight studies included an adequate description of diagnostic criteria and of procedures used to assure adherence to the criteria, 54 used appropriate end points, two assembled inception cohorts, 10 included an adequate description of end point surveillance, 22 adequately reported and analyzed censored patients, and 10 included a multivariate analysis for predictive variables. No study adhered to all six principles, but two adhered to the three most important ones (appropriate end points, inception cohort, and adequate reporting and analysis of censored patients). Aspects of prognosis after transient ischemia that have not been completely investigated include the severity of subsequent strokes and methods for estimating the outcome risk for individual patients. We conclude that only a few published investigations on prognosis after transient ischemia are methodologically complete. This finding helps explain why it is difficult to interpret many studies. Further research is needed and should target underinvestigated topics. PMID- 1926254 TI - Clinical and hemodynamic aspects of low-flow infarcts. AB - We used single-photon emission computed tomography to measure cerebral blood flow, cerebral blood volume, and cerebral perfusion reserve and transcranial Doppler sonography with CO2 stimulation to assess hemispheric vasomotor reactivity in 37 patients and in normal controls. Computed tomography and magnetic resonance imaging were performed to differentiate morphologically low flow infarcts (n = 17) from territorial infarcts (n = 20). In patients with either type of infarct, blood flow was decreased and blood volume was increased in the infarcted areas compared with the same areas in the controls. Perfusion reserve and vasomotor reactivity were significantly reduced in patients with territorial infarcts and carotid artery occlusions (n = 12) and even more reduced in patients with low-flow infarcts (p less than 0.001). Both parameters were normal in patients with cardiac embolic territorial infarcts (n = 8). In patients with territorial infarcts, blood flow and perfusion reserve changes were restricted to the infarcted areas, whereas in patients with low-flow infarcts, regions of decreased perfusion reserve considerably exceeded the area of the infarct. Low-flow infarcts are related to the hemodynamic effects of severe extracranial carotid artery disease. PMID- 1926255 TI - Basilar branch pontine infarction with prominent sensory signs. AB - We identified 10 patients with acute pontine infarction and specific sensory findings. Two patients had pure sensory symptoms, two had sensory complaints of the hand and mouth, and the other six had hemisensory loss referable to medial lemniscal or spinothalamic tract dysfunction but localized to one limb, to an arm and leg, or to the face, characteristic of stroke localized to the cerebral hemisphere. All patients had magnetic resonance imaging showing infarction of the medial or lateral pontine tegmentum and a patent basilar artery. No definite source for cardiogenic thromboembolism was found. Infarcts in the midline extending from the base of the pons posteriorly into the tegmentum suggested basilar branch occlusion, while infarcts involving only part of the tegmentum probably resulted from small penetrator branch occlusion. Vertigo, light headedness, or cranial nerve dysfunction suggested a pontine location of neurological dysfunction in these patients, but the nature of the sensory findings did not always predict the lateral, medial, inferior, or superior extent of tegmental infarction. PMID- 1926256 TI - A pilot study of hyperbaric oxygen in the treatment of human stroke. AB - We administered hyperbaric oxygen or air in a double-blind prospective protocol to 39 patients with ischemic cerebral infarction. We interrupted the study when we noticed what appeared to be a trend favoring the air-treated patients, whose neurological deficits were less severe (mean +/- SEM score on graded neurological examination: air, 25.6 +/- 4.9; oxygen, 34.5 +/- 7.5) and whose infarcts were smaller (air, 29.0 +/- 12.2 cm3; oxygen, 49.2 +/- 11.7 cm3) at 4 months. The trend, we decided, was probably an artifact of the randomization process. Nevertheless, we chose not to resume the trial because the treatment was difficult to administer by schedule (for various reasons the treatment protocol was broken in 15 of the 39 patients), was poorly tolerated (eight of the 39 patients refused to continue treatments), and did not produce dramatic improvement. PMID- 1926257 TI - Assessment of cerebral autoregulation dynamics from simultaneous arterial and venous transcranial Doppler recordings in humans. AB - We investigated the validity of transcranial Doppler recordings for the analysis of dynamic responses of cerebral autoregulation. We found no significant differences in percentage changes among maximal (centerline) blood flow velocity, cross-sectional mean blood flow velocity, and signal power-estimated blood flow during 24-mm Hg stepwise changes in arterial blood pressure. We investigated blood flow propagation delays in the cerebral circulation with simultaneous Doppler recordings from the middle cerebral artery and the straight sinus. The time for a stepwise decrease in blood flow to propagate through the cerebral circulation was only 200 msec. Brief (1.37-second) carotid artery compression tests also demonstrated that the volume compliance effects of the cerebral vascular bed were small, only about 2.2% of normal blood flow in 1 second. Furthermore, transients associated with inertial and volume compliance died out after 108 msec. We also investigated the hypothesis that autoregulatory responses are influenced by hyperventilation using the same brief carotid artery compressions. One second after release, the flow index increased by 17% during normocapnia and 36% during hypocapnia. After 5 seconds, the flow index demonstrated a clear oscillatory response during hypocapnia that was not seen during normocapnia. These results suggest that the intact human cerebral circulation in the absence of pharmacological influences does not function as predicted from pial vessel observations in animals. PMID- 1926259 TI - Effects of nicardipine on cerebral vascular responses to hypocapnia and blood flow velocity in the middle cerebral artery. AB - We noninvasively evaluated the effects of nicardipine on cerebral vascular responses to hypocapnia and blood flow velocity in the middle cerebral artery of 10 patients aged 17-60 (mean +/- SD 46.1 +/- 11.8) years. During fentanyl/diazepam/nitrous oxide anesthesia, mean blood flow velocity in the middle cerebral artery was measured and cerebral vascular reactivity to hypocapnia induced by hyperventilation was assessed before and during the administration of nicardipine. Mean blood flow velocity was measured using transcranial Doppler ultrasonography, and the cerebral vascular reactivity was expressed as the percentage change in mean blood flow velocity per unit change in end-tidal PCO2. During the administration of 5.1 +/- 1.3 micrograms/kg/min nicardipine, which caused a 26% reduction in mean arterial blood pressure, mean blood flow velocity increased significantly from 57.2 +/- 19.2 to 64.2 +/- 21.6 cm/sec (p less than 0.01, paired t test), whereas cerebral vascular reactivity showed no significant change (4.0 +/- 1.2% and 4.9 +/- 2.5%, respectively). In conclusion, during fentanyl/diazepam/nitrous oxide anesthesia in patients, cerebral vascular reactivity to hypocapnia was maintained and nicardipine-induced hypotension resulted in increased middle cerebral artery blood flow velocity with maintenance of carbon dioxide reactivity to hypocapnia. PMID- 1926258 TI - Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. CHS Collaborative Research Group. AB - Carotid sonography is being performed on more than 5,000 participants in the Cardiovascular Health Study, a prospective, multicenter study of cardiovascular disease in men and women aged 65 years and older. The sonographic methods used to examine and measure the extracranial carotid arteries are described. Initial validation studies were performed on 61 subjects with a mean age of 68.6 years. Analysis of within- and between-sonographer differences and between-reader differences were performed for selected variables. In general, the mean absolute differences for within- and between-sonographer comparisons were small, with even less variability between readers. Variability was less for the common carotid artery than for the internal carotid artery. These data suggest that carotid sonography is a reliable and reproducible method for use in the study of carotid atherosclerosis in population studies. PMID- 1926260 TI - Cerebrovascular disease in Saudi Arabia. AB - We studied the pattern and outcome of strokes in 200 Saudi patients. Cerebral infarction constituted 87% of strokes, subarachnoid hemorrhage 4.5%, cerebral hemorrhage 6.5%, and venous infarction 2%. The vessel most commonly involved was part or all of the middle cerebral artery, constituting 52% (90) of the 174 arterial infarcts. Lacunar infarcts were seen in 21% (37) of the patients with arterial infarcts. Among all 200 patients, 8% died and 8% had secondary generalized seizures. Hypertension occurred in 41% of the 174 patients with arterial infarcts and 62% of the 13 with cerebral hemorrhages. The highest incidence of hypertension as a risk factor was among those with lacunar infarcts (81%), ganglionic cerebral hemorrhages (80%), and infarcts of deep branches of the middle cerebral artery (57%). Embolic infarcts due to rheumatic heart disease constituted 11% of all arterial infarcts. We conclude that our pattern of strokes is similar to that of the west rather than that of the Japanese, but with less frequent arteriovenous malformations and aneurysms. PMID- 1926261 TI - Mechanisms of impaired endothelium-dependent cerebral vasodilatation in response to bradykinin in hypertensive rats. AB - Bradykinin produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats than in normotensive Wistar-Kyoto rats. The goals of this study were to determine the mediator of bradykinin-induced dilatation in cerebral arterioles of rats and to determine whether responses to this mediator are altered in hypertensive rats. Diameter of pial arterioles (20-65 microns) was measured using intravital microscopy in 18 normotensive and 17 hypertensive rats. Superfusion of 3 x 10(-7) M bradykinin dilated pial arterioles by 53 +/- 4% (mean +/- SEM) in normotensive rats but only 33 +/- 6% in hypertensive rats (p less than 0.05 versus normotensive rats). Vasodilatation in response to bradykinin was almost completely inhibited by 280 units/ml catalase in both normotensive and hypertensive rats (n = 7 and n = 7, respectively) whereas 150 units/ml superoxide dismutase (n = 6 and n = 5, respectively) and 1 mM deferoxamine (n = 5 and n = 5, respectively) did not attenuate bradykinin-induced vasodilatation. These findings suggest that hydrogen peroxide is the mediator of bradykinin-induced dilatation in cerebral arterioles of rats. We also examined responses of cerebral arterioles to hydrogen peroxide in five normotensive and six hypertensive rats. Dilator responses of cerebral arterioles to 3.2 x 10(-5) M to 1.6 x 10(-4) M hydrogen peroxide did not differ in normotensive and hypertensive rats, which suggests that impaired dilatation of cerebral arterioles in response to bradykinin is not related to altered responsiveness of smooth muscle to an endothelium-derived relaxing factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1926262 TI - Activation of the protein kinase C-mediated contractile system in canine basilar artery undergoing chronic vasospasm. AB - We previously suggested that activation of the protein kinase C-mediated contractile system may participate in the occurrence of chronic cerebral vasospasm. In the present study, we compared segments of normal beagle basilar arteries in vitro with segments of arteries undergoing chronic vasospasm to determine the responsiveness to various agonists such as serotonin, prostaglandin F2 alpha, and phorbol 12,13-diacetate as well as to external Ca2+. We also compared the effects of W-7 (a calmodulin inhibitor), nicardipine (a calcium channel blocker), and H-7 (a protein kinase C inhibitor) on the spontaneous tonus of arterial segments stabilized at a resting tension of 3 g. Compared with normal segments, the responsiveness to each agonist in segments undergoing vasospasm was essentially unchanged whereas the the responsiveness to external Ca2+ was significantly decreased (p less than 0.001). In segments undergoing vasospasm the decrease in resting tension induced by W-7 was markedly diminished (p less than 0.01), that induced by nicardipine was unchanged, and that induced by H-7 was significantly increased (p less than 0.01). Our results indicate that spontaneous tonus due to activation of the protein kinase C system is significantly augmented in segments undergoing vasospasm. Thus this system, rather than the Ca2+/calmodulin system, appears to play a major role in the occurrence of chronic vasospasm. PMID- 1926263 TI - Quicker metabolic recovery after forebrain ischemia in rats treated with the antioxidant U74006F. AB - We used phosphorus-31 nuclear magnetic resonance spectroscopy in a rat model of 10 minutes' severe incomplete forebrain ischemia (two-vessel occlusion with hypotension) to study the effects of preischemic and postischemic treatment with 3 mg/kg i.v. U74006F on the recovery of high-energy phosphates and intracellular pH during early reperfusion. The mean +/- SD time to 85% recovery of phosphocreatine was 14.1 +/- 8.4 minutes in the control group (n = 10) compared with 6.6 +/- 3.5 minutes (p less than 0.05) in the preischemic (n = 8) and 4.2 +/ 1.0 minutes (p less than 0.001) in the postischemic (n = 11) treatment groups. The mean +/- SD time to 80% recovery of adenosine triphosphate was 15.4 +/- 8.5 minutes in the control group compared with 6.3 +/- 1.8 (p less than 0.005) and 5.4 +/- 2.8 (p less than 0.001) minutes in the preischemic and postischemic treatment groups, respectively. There were no differences in intracellular pH between the control and either of the treatment groups. We conclude that U74006F led to quicker recovery of high-energy phosphates during early reperfusion, and this beneficial effect was also seen with postischemic treatment. PMID- 1926264 TI - Severe anemia associated with transient neurological deficits. AB - In two patients with carotid artery stenosis and anemia, neurological deficits appeared whenever the hemoglobin level fell below a critical level of 5-6 g/dl and resolved with correction of the anemia. Profound anemia should be considered as a cause of focal neurological deficit, especially if there is evidence of cerebral atherosclerosis. PMID- 1926266 TI - Cardiac imaging in stroke. PMID- 1926265 TI - Recurrent embolic stroke and cocaine-related cardiomyopathy. AB - Ischemic stroke temporally related to cocaine abuse has become increasingly common in young adults. Despite this relation, however, the pathogenesis of infarction in many of these patients remains obscure. I report the case of a 39 year-old man who developed occlusion of the frontopolar branches of the left middle cerebral artery 1 hour after intravenous cocaine use. Eleven days later he developed occlusion of the superior division of the right middle cerebral artery. In this case the mechanism of infarction was clearly cardiogenic embolization. Chest radiograph and echocardiogram revealed dilated cardiomyopathy with left ventricular thrombi. No cause other than cocaine abuse was found for his cardiomyopathy. This is the second reported case of cocaine-related cardiomyopathy presenting as embolic stroke and associated with intracavitary thrombus. Such an association may be more common than previously thought. Thorough cardiac evaluation in all patients with ischemic stroke related to cocaine abuse is appropriate. PMID- 1926267 TI - Cerebral arterial thrombosis preceding ulcerative colitis. PMID- 1926268 TI - Aspirin and hemorrhagic stroke. PMID- 1926269 TI - The lacune hypothesis. PMID- 1926270 TI - Enantioselective hydroxylation of nortriptyline in human liver microsomes, intestinal homogenate, and patients treated with nortriptyline. AB - The enantioselectivity of hydroxylation of nortriptyline (NT) to E-10 hydroxynortriptyline (E-10-OH-NT) was studied in human liver microsomes, intestinal homogenate, and patients treated with NT. The rate of formation of (-) E-10-OH-NT was higher than that of (+)-E-10-OH-NT both in the liver microsomes and in the intestinal homogenate. Quinidine, a prototype competitive inhibitor of the cytochrome P450IID6 ("debrisoquin hydroxylase"), inhibited the formation of ( )-E-10-OH-NT in a concentration-dependent manner in liver microsomes, while the formation of (+)-E-10-OH-NT was hardly affected. This indicates that P450IID6 catalyzes the hydroxylation of NT in a highly enantioselective manner to (-)-E-10 OH-NT in the liver. Another P450 isozyme besides IID6 seems to be responsible for the formation of the (+)-enantiomer in the liver. In intestinal homogenate, the formation of both enantiomers of E-10-OH-NT was inhibited to about the same extent by quinidine, the maximum inhibition being much less than in the liver. In the urine of six patients treated with NT, the (-)-enantiomer accounted for 91 +/ 2% of the unconjugated E-10-OH-NT, and for 78 +/- 6% of the glucuronide conjugates. The study shows that NT is hydroxylated in a highly enantioselective way, probably catalyzed by the polymorphic P450IID6, to (-)-E-10-OH-NT both in vitro in human liver as well as in vivo in patients treated with the drug. PMID- 1926271 TI - Population pharmacokinetics of rectal theophylline in neonates. AB - The population pharmacokinetics of theophylline were studied in 35 neonates receiving aminophylline suppositories for the treatment of apnoea of prematurity. Routinely measured theophylline serum concentrations (n = 138, range 3-20 mg/L) were modelled in NONMEM according to a one-compartment model. The influence of a number of clinical and demographic factors, e.g., weight (range 0.8-2.5 kg) and postnatal age (2-80 days), on clearance/bioavailability (CL/F) and volume/bioavailability (V/F) was investigated. Both these parameters were found to significantly correlate to weight alone in a directly proportional manner: CL/F = 40 +/- 2 ml/h/kg and V/F = 1.3 +/- 0.2 L/kg. The absorption was best described by a first-order process, having a half-life of 1.6 +/- 0.7 h. The interindividual variability in CL/F was 25%, whereas the same estimates in V/F and in the first-order absorption rate constant could not be obtained. The residual variability in theophylline concentrations was modelled with additive error with an estimated standard deviation of 1.78 mg/L. From these results, it was concluded that rectal administration of aminophylline in neonates is a therapeutically acceptable alternative to oral administration. The convenience gained by rectal, compared to oral, administrations may compensate, in many instances, for the possibly slightly higher variability in CL/F of the former. PMID- 1926272 TI - Carbamazepine age-dose ratio relationship in children. AB - Steady-state plasma carbamazepine (CBZ) concentrations were measured in 196 pediatric inpatients taking CBZ alone or CBZ combined with other drugs. The steady-state CBZ concentrations divided by the daily administered dose (dose ratio, reciprocal of apparent clearance) increased significantly (r = 0.183, p less than 0.01) with age. The correlation between dose and CBZ concentration, while significant (r = 0.265, p = 0.023), was weak because of wide interindividual differences in dose ratio. There was a negative correlation between CBZ daily dose and CBZ dose ratio. This negative correlation was significant in children 4-6 (r2 = 0.481, p less than 0.01), 7-11 (r2 = 0.399, p less than 0.01), and greater than 11 years of age (r2 = 0.401, p less than 0.01), but not in children less than 4 years of age (r2 = 0.172, p greater than 0.1). The CBZ dose ratio was significantly (p less than 0.001) lower in patients taking CBZ in combination with more than one other antiepileptic drug compared with those on CBZ monotherapy. No significant (p greater than 0.1) difference in CBZ dose ratio was found between male and female patients. These findings suggest that CBZ clearance was influenced by age, dose, and comedication with more than one other antiepileptic drug but not sex. The concentration necessary for efficacy is a clinical, not an analytical decision. However, the dose concentration relationships show that recommended pediatric CBZ doses of 10-30 mg/kg/day are not enough to attain published therapeutic CBZ concentrations in many children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1926273 TI - The pharmacokinetics of captopril in infants with congestive heart failure. AB - The use of the angiotensin-converting enzyme inhibitor captopril in infants with congestive heart failure (CHF) has been empirical owing to a lack of relevant pharmacokinetic data. To determine standard pharmacokinetic parameters for the drug in this population, we administered captopril, 1 mg/kg, orally to 10 infants aged 6.8 +/- 4.6 months. Sequential plasma unchanged and total (sum of unchanged and dimerized) captopril concentrations were determined using a high-performance liquid chromatographic method. Arterial pressure, systemic and pulmonary resistance, heart rate, and respiratory rate were all significantly decreased 1 h after the first dose of captopril. Plasma renin activity was not significantly increased. For unchanged captopril, the maximum concentration (Cmax) was 350 +/- 184 ng/ml; the time to Cmax (Tmax), 1.6 +/- 0.4 h; elimination half-life (t1/2), 3.3 +/- 3.3 h; oral clearance (Clo), 1.1 +/- 0.4 L/h/kg. For total captopril, Cmax was 1,088 +/- 621 ng/ml; Tmax, 2.7 +/- 1.1 h; t1/2, 3.4 +/- 1.0 h. Thus, we conclude that the pharmacokinetic parameters for captopril in infants with CHF are within the range reported for adults with CHF. Also, the hemodynamic changes, measured 1 h after the first dose, indicate that the acute effects of captopril in infants with CHF are beneficial. PMID- 1926274 TI - Making digoxin therapeutic drug monitoring more effective. AB - Digoxin is an important drug in the treatment of patients with either congestive heart failure or atrial arrhythmia. Because of its narrow therapeutic range, digoxin serum concentrations are commonly monitored in both inpatients and outpatients. However, with the costs of health care skyrocketing, there is debate whether such therapeutic drug monitoring (TDM) is cost-effective. To reduce the number of samples drawn too soon after a previous dose and in an effort to improve digoxin TDM at this teaching hospital, a new dosing and monitoring policy was initiated. This policy involved uniform digoxin dosing at 5 p.m. (1700 h) for all inpatients and serum drug measurements at 7 a.m. (0700 h) the next day. By coordinating the time of dosing to be greater than 12 h prior to serum digoxin analysis, the number of inappropriate digoxin serum determinations have been reduced. This new protocol has increased the effectiveness of the toxicology laboratory and enhanced the efficiency of the house staff. Other issues concerning digoxin TDM are also addressed. These findings can be generalized to all drugs that are monitored at any hospital and can result in a significant cost savings and decrease the time spent analyzing inappropriate data. PMID- 1926275 TI - Determination of 6-mercaptopurine in acute lymphoblastic leukemia patients' plasma by high-performance liquid chromatography. AB - A simple, selective, sensitive, and rapid high-performance liquid chromatography (HPLC) method is described for the quantitation of 6-mercaptopurine (6-MP) in plasma of patients with acute lymphoblastic leukemia (ALL). Pharmacokinetic data are presented for seven children with ALL receiving 6-MP therapy. A sensitivity of greater than or equal to 2 ng/ml in plasma was achieved on a reverse-phase octadecylsilane column using an HPLC system following a cleanup step with a solid phase extraction cartridge. The chromatogram was monitored at 325 nm. Analytical recovery of 6-MP was 90%. The coefficients of variation for intra- and interday variabilities were 2.51 and 4.23%. This assay method is clinically useful for pharmacokinetic studies of 6-MP in ALL patients. PMID- 1926276 TI - A simple, rapid method for the simultaneous determination of morphine and its principal metabolites in plasma using high-performance liquid chromatography and fluorometric detection. AB - This article describes a high-performance liquid chromatography (HPLC) method for the simultaneous determination of morphine (M) and its principal metabolites morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), and normorphine (NM) in plasma. All four compounds are extracted from plasma using a C8 solid-phase extraction column, separated by reverse-phase HPLC on a C18 analytical column, and detected by spectrofluorometry at 210 nm excitation wavelength. The method takes advantage of the compounds' native fluorescence, so that derivitization is not required. Samples have been quantified over a concentration range of 25-100 ng/ml M and NM, 50-200 ng/ml M3G, and 100-300 ng/ml M6G, using nalorphine (500 ng/ml) as internal standard. Within-run and between-run errors were less than 10% for morphine and less than 13% for all the metabolites. The lower limit of quantitation for morphine is 10 ng/ml. The accuracy of the method was confirmed by including quality controls fitted to the standard curves of each compound. The assay described in this article represents a simplification of previous versions of the method, which included cumbersome extraction procedures and multiple detectors. For the first time, an internal standard has been employed. The assay is reliable and easy to use and can be performed in any therapeutic drug monitoring laboratory. PMID- 1926277 TI - Assay of theophylline: in vivo and in vitro evaluation of dry chemistry and immunoassay versus high-performance liquid chromatography. AB - In the last decade, kits using dry chemistry have been introduced for analysis of theophylline in biological fluids. We investigated the performance of Ames Seralyzer and Kodak Ektachem 700XR. They were compared to an enzyme immunotechnique (Syva EMIT) and high-performance liquid chromatography (HPLC). Mixed sera from theophylline-treated patients at concentrations of 20, 50, and 80 mumol/L were used. We also investigated the performance of the various methods when assaying theophylline concentrations obtained from individual patients treated or intoxicated with theophylline (n = 35 patients). In within-day analysis, the EMIT method deviated +1- + 9%. the Ektachem 700XR method deviated +2- + 8%, and the Seralyzer method deviated at least + 18% compared to HPLC. Within-day variability was low for all 4 methods. A similar pattern was seen during between-day assay. In five intoxicated patients, EMIT, Seralyzer and Ektachem 700XR deviated at least + 10% compared to HPLC. The Ektachem 700XR method deviated +16- + 36% compared to HPLC, when samples of 240 mumol/L and above were analyzed. Our study shows that theophylline assay kits cannot be recommended in drug analytical laboratories unless specific backup methods are available. EMIT showed the best performance compared to HPLC. Ektachem 700XR gave good results at therapeutic drug concentrations, but was not reliable in intoxicated patients or in those with decreased kidney function. PMID- 1926278 TI - Effect of serum separator tubes on free and total phenytoin and carbamazepine serum concentrations. AB - The effect of serum separator tubes (SSTs) on free and total serum phenytoin and carbamazepine concentrations was determined by comparing standard no-additive tubes with SSTs (Becton Dickinson SST and Terumo Autosep). The influence of time prior to centrifugation, sample volume, and initial drug concentration on the effects were also studied. Results were analyzed using repeated measures two-way analysis of variance with tube type and either time, sample volume, or concentration as main effects. The most significant reductions noted were with Becton Dickinson SSTs in free and total serum phenytoin and total carbamazepine concentrations, where all reductions were less than 10%. The only factor to significantly influence extent of reduction was the effect of time on total serum phenytoin concentration in Becton Dickinson SSTs. Terumo Autosep tubes caused no major reductions in free or total phenytoin or carbamazepine serum concentrations. Autosep tubes should provide accurate measurements of total and free serum phenytoin and carbamazepine concentrations. With Becton Dickinson SSTs, the reductions noted in free and total phenytoin and total carbamazepine concentrations were not large enough to preclude their clinical use. Becton Dickinson SSTs should not be used for determining free or total phenytoin or total carbamazepine concentrations for purposes of research. PMID- 1926280 TI - Determination of vigabatrin in plasma by reversed-phase high-performance liquid chromatography. AB - A method is described for the determination of vigabatrin in 50 microliters of plasma by isocratic high-performance liquid chromatography using fluorescence detection. The procedure involves protein precipitation with methanol followed by precolumn derivatisation with o-phthaldialdehyde reagent. Separation of the derivatised vigabatrin was achieved on a Microsorb C18 column using a mobile phase of 10 mM orthophosphoric acid:acetonitrile:methanol (6:3:1) at a flow rate of 2.0 ml/min. Assay time is 15 min and chromatograms show no interference from commonly coadministered anticonvulsant drugs. The total analytical error within the range of 0.85-85 micrograms/ml was found to be 7.6% with the within replicates error of 2.76%. The minimum detection limit was 0.08 micrograms/ml and the minimum quantitation limit was 0.54 micrograms/ml. PMID- 1926279 TI - Application of the Empore solid-phase extraction membrane to the isolation of drugs from blood. I. Amiodarone and desethylamiodarone. AB - We describe the use of a new form of solid-phase material, the Empore solid-phase extraction membrane (SPEM), for therapeutic drug monitoring. We evaluated the new extraction procedure with the companion high-performance liquid chromatographic (HPLC) method for the antiarrhythmic drug amiodarone and its metabolite, desethylamiodarone, in patients' serum. Acidified serum (250 microliters) was passed through an octyl (C8) SPEM secured in an MF-1 microfilter unit. Serum proteins and potential interferences were removed with an acetonitrile:water wash, and the retained drugs eluted with HPLC mobile phase. This eluate was injected directly onto the analytical column. Both drugs averaged 85% recovery with a linear response from a lower limit of detection at 0.05 mg/L up to 6 mg/L, and between-run precision coefficients of variation ranging from 3.1 to 6.4% over the concentration range of 0.5-3.0 mg/L. We observed significant advantages of the novel SPEM over conventional liquid-liquid or large-particle size solid-phase sorbents packed in cartridges. Minimal amounts of solvents were required, elution volume was smaller, time-consuming evaporating/concentrating steps that can influence drug stability were avoided, and little throw-away material was generated. Only the small membrane was discarded. PMID- 1926281 TI - An expedient liquid chromatographic micromeasurement of isoniazid in plasma by use of electrochemical detection. AB - We describe a sensitive and expedient microassay of isoniazid in plasma by use of electrochemical detection in conjunction with a radial compression liquid chromatography. Diphenylcarbazide was used as an internal standard and the separation was achieved on a 10-micron, 8 mm x 10 cm C18 (12% carbon load) cartridge. A mixture of 10 mM sodium dibasic phosphate solution (adjusted to pH 7 with phosphoric acid) and methanol (93.5:6.5, by volume) was used as a mobile phase at a flow rate of 4 ml/min. After dilution with an equal volume of aqueous solution of the internal standard (6.667 microM), the plasma sample (50-150 microliters) was deproteinized by use of an Amicon Centrifree-MS ultrafilter at 2,000 g. No interference from any endogenous substance or concomitantly used drug was observed, and the assay was highly linear (r greater than 0.9994) in the concentration range examined (0.146-145.8 microM). The intra- and interrun precision was equally good, with coefficients of variation of less than 3.13 and less than 5.4%. We are currently using this method for monitoring isoniazid in patients treated with this drug for tuberculosis. PMID- 1926282 TI - Particle concentration fluorescence immunoassay of gentamicin. AB - We report the development of a particle concentration fluorescence immunoassay (PCFIA) for gentamicin using commercially available reagents. The solid phase consists of 0.8 microns polystyrene spheres to which gentamicin antibody is noncovalently bound. Fluorescein-labeled gentamicin serves as the tracer. The assay is carried out on 96-well reaction plates and read using an automated instrument. The assay is accurate over the range of gentamicin concentrations commonly encountered in clinical practice, with day-to-day coefficients of variation of 3-7%. As little as 0.01 mg/L of gentamicin can be detected when sample predilution is omitted. PCFIA is compared with Abbott TDX fluorescence polarization immunoassay for the measurement of serum gentamicin concentrations in routine clinical specimens. PMID- 1926283 TI - Measurement of ciprofloxacin in human plasma, whole blood, and erythrocytes by high-performance liquid chromatography. AB - A simple, rapid, and accurate high-performance liquid chromatographic method using fluorescence detection is described for the measurement of ciprofloxacin in plasma, whole blood, and erythrocytes. Ciprofloxacin and the internal standard difloxacin were separated on a mu-Bondapak C18 column (30 cm x 3.9 mm inside diameter, 10 microns particle size), using a mobile phase of 0.1 M phosphate buffer (pH 2.5):acetonitrile (75:25, vol/vol). The retention times were 5.1 min for ciprofloxacin and 7.9 min for difloxacin. The compounds were extracted from the three biological fluids using protein precipitation followed by a single-step liquid-liquid extraction. The assay is precise, with interassay coefficients of variation of less than or equal to 9.1% and an accuracy of less than or equal to 7.4% at 0.5 and 5.0 micrograms/ml (n = 5). The mean extraction recoveries of ciprofloxacin in plasma, whole blood, and erythrocytes were 84.4, 63.9, and 48.0%. The limit of detection for ciprofloxacin is 25 ng/ml. Ciprofloxacin concentrations in the three biological fluids were measured in patients with uncomplicated falciparum malaria to demonstrate the application of the method. PMID- 1926284 TI - Monitoring serum levels of gentamicin to develop a new regimen for gentamicin dosage in newborns. AB - The newborns studied had gestational ages ranging between 23-44 weeks, weights ranging between 725-4510 g, and were treated with standard doses of gentamicin (5.2 +/- 1.0 mg/kg/day). The gentamicin serum peak and trough levels were unrelated to administered doses, and a large proportion of patients had low (peak less than 4 micrograms/ml in 12%) or potentially toxic concentrations (trough greater than 2 micrograms/ml in 55%). The pharmacokinetic parameters (t1/2e, 8.2 +/- 4.8 h and Vd, 0.64 +/- 0.22 L/kg) varied markedly between patients. The newborn's weight, age, gestational age, and serum creatinine were factors of importance for the variability of gentamicin serum levels. The newborns were divided into four groups: gestational period less or more than 37 weeks and age below or above 7 days. These groups had different gentamicin serum levels and pharmacokinetic parameters. The results suggest that a gentamicin dosage regimen based on the division of newborn patients into subgroups or calculated from individual pharmacokinetic characteristics would decrease the risk of obtaining potentially toxic or subtherapeutic gentamicin concentrations after the use of standard doses. PMID- 1926286 TI - Age-associated involution: significance of a physiologic process. PMID- 1926285 TI - Changes in gentamicin serum levels and pharmacokinetic parameters in the newborn in the course of treatment with aminoglycoside. AB - Gentamicin serum levels were determined in an unselected group of newborns treated with standard doses of the drug to study the changes in pharmacokinetic parameters (trough and peak serum levels/dose ratio, serum level increases/dose ratio, elimination half-life, and distribution volume) 48, 96, and 144 h after commencing treatment. However, no significant changes in the pharmacokinetic parameters were found in different groups of neonates, classified according to gestational age and days of life during the study period. It appears that the dose of gentamicin once it has been individually established does not have to be changed, at least during the first week of treatment. PMID- 1926287 TI - Murine CD4-CD8- thymocytes are stimulated by interleukin-2 to proliferate in vitro in chemically defined medium. AB - The ability of fetal and young adult CD4-CD8- thymocytes to proliferate in chemically defined (serum-free) medium in the presence and absence of IL-2 was examined. Dissociated thymocytes from day 15 and older fetal mice proliferated in vitro in the presence but not the absence of IL-2. The degree of proliferation was increased by including IL-1 with the IL-2. Inclusion of IL-1 in cultures of fetal thymocytes was associated with an increase in the number of IL-2 receptor positive cells, relative to cultures containing IL-2 alone. Although unfractionated thymocytes failed to proliferate in chemically defined medium, CD4 CD8- cells purified from thymic cell suspensions from young adult mice from several inbred strains proliferated to a limited extent in the absence of added cytokines. Proliferation was augmented 40-100 fold by inclusion of IL-2 in cultures. IL-1 stimulated some proliferation by young adult CD4-CD8- cells, but, unlike the effect of IL-1 and IL-2 on fetal thymocytes, combination of IL-1 with IL-2 did not have a notable additive effect on IL-2 induced proliferation. Proliferation stimulated by both IL-1 and IL-2 was completely abrogated by inclusion of anti-IL-2 receptor antibody in the cultures. Thymocytes from F1 progeny of inbred strains of mice proliferated to a greater extent in the absence of IL-2 than did thymocytes from either parent strain, although the response to IL-2 was not significantly different. The data demonstrate that both fetal and adult CD4-CD8- thymocytes area capable of proliferating in response to IL-2 in vitro, suggesting that, as is the case during antigen specific responses by mature T cells, IL-1 and IL-2 cooperate to stimulate T cell proliferation during development in vivo. PMID- 1926288 TI - Binding and internalization of gold-labeled insulin complex by thymic cells. AB - Colloidal gold-labeled insulin complex was used for the ultrastructural visualization of insulin binding sites on the cell surface and to study the intracellular pathway of insulin. Thymic epithelial cells and thymic lymphoid cells from mammalian fetuses (mouse, rat, man) were investigated. The results show that all epithelial cells and some lymphoid ones bind insulin during fetal life. Certain fine structural features (single gold particles, patches and clusters of gold granules on the cell membrane) which are common for both kinds of thymic cell lines are established. Uncoated pinocytotic invaginations (more rarely via coated pits), tubulo-vesicles, uncoated vesicles, intermediate filaments and microtubules are related to insulin gold complex intracellular pathway in the epithelial cells. However, these peculiarities as a whole are noted typically in the lymphoid cells. These data suggest that the ability to cap and to internalize IGC is directly associated with thymic cell type and similar in principle to both cellular types (epithelial and lymphoid cells) in all mammalian fetuses studied. PMID- 1926290 TI - Characterisation of two different subpopulations of axial organ cells of Asterias rubens by the use of lectins. PMID- 1926289 TI - Thymus biopsy in patients with AIDS and ARC. PMID- 1926291 TI - Hypothesis: involution of the thymus with aging--programmed and beneficial. AB - This is an attempt to find a teleological rationale for the involution of the thymus with aging. The thymus is the first organ in the body to age, which seems incongruent considering its cardinal role in the immune system. An analogical incongruency can be seen in the fact that acute stress is generally accompanied by a reversible involution of the thymus. We hypothesized earlier, that this reversible involution might protect the organism from the danger of autoimmune diseases. It stands to reason that, in nature, conditions leading to stress frequently entail massive tissue destruction. This may cause the appearance of "altered self" components, leading to the formation of autoantibodies. Hence, the temporary shut-off of thymic activity would be beneficial. A similar argument holds in the case of aging and will be elaborated as follows: 1) Formation of antibodies per se entails the danger of autoimmune mechanisms, hence the process is controlled at various levels; 2) The aging process is characterized by the increasing appearance of non-self components as a result of DNA errors and post translational changes due to free radicals and other high energy oxygen derivatives; 3) Early involution serves, in our opinion, to reduce the risk of autoimmune diseases which increases with aging, and should therefore be regarded as an adaptation of the organism to aging; 4) If this notion proves to be correct the desirability of restoring full thymic activity in old people becomes questionable. PMID- 1926292 TI - High level of CD1a putative peripheral blood precursors of epidermal Langerhans cells after bone marrow transplantation. PMID- 1926294 TI - Localization of sex steroid receptor cells, with special reference to thymulin (FTS)-producing cells in female rat thymus. AB - Using monoclonal antibodies against progestin receptors (PR) and estrogen receptors (ER), and polyclonal antibodies to thymulin (FTS) and keratin, localization of the sex steroid receptors was studied immunohistochemically in ovariectomized estrogen-treated rat thymus, with special reference to FTS producing cells. Both ER- and PR-immunostained cells were mainly localized in the medullary region, especially at its periphery (i.e., the corticomedullary junction). A few cells were also situated in the subcapsular area. They were medium- to large-sized and had a dendritic cell process, some of which were immunohistochemically keratin- and FTS-positive, indicative of reticuloepithelial (RE) cells. Hassall's corpuscles were also receptor-positive and FTS-positive. T cells were not immunostained with anti-ER, anti-PR or anti-FTS. Light microscopically, both ER and PR immunostainings were localized in the cytoplasm and/or nucleus of keratin-stained RE cells. Electron microscopically, both steroid receptors were shown more precisely to distribute as aggregates of osmiophilic black dots on polysomes and perinuclear space in the cytoplasm and on the euchromatin area in the nucleus. These results suggest that the sex steroids E and P exert their effects through receptors within RE cells which produce FTS to regulate T-cell differentiation. PMID- 1926293 TI - Age-dependent changes in the proportion of macrophages in primary thymus non lymphoid cell cultures. AB - Primary murine thymus cell cultures consist of thymus epithelial cells, macrophages and interdigitating dendritic cells. Results of the present study indicated that the proportion of macrophage-like cells in cultures was directly related to the age of the thymus donors through 7 weeks of age. We standardized procedures to compare primary thymic cultures derived from mice, 1 day to 115 days of age. Cultures were grown 6 to 8 days and then tested for nonspecific esterase, acid phosphatase, phagocytosis of latex beads, Fc receptors, and MAC-1 staining. Less than 10% macrophage-like cells were identified in cultures from mice 1 to 3 days-old, but the proportion increased to 50% macrophage-like cells in cultures from 7 week-old mice. Thereafter the proportion plateaued although there was considerable variation among older mice. Further studies showed that the proportions of macrophage-like cells was not affected by the number of cells initially seeded into culture, nor by the amount of serum added to the culture medium. These data suggest that macrophage/interdigitating cell precursors immigrate into the thymus for 4 to 6 weeks after birth and support the hypothesis that these precursors may be influenced to differentiate into thymus macrophages or interdigitating cells by the thymic microenvironment. PMID- 1926295 TI - [Depression]. PMID- 1926296 TI - [The family physician and depression in the elderly. A pilot study of prevalence of depressive symptoms and depression in the elderly in 2 family practices]. AB - A pilot-study on the prevalence of depressive symptoms and GPs' assessment of depressed mood in elderly attenders of two general practices. The aim of this pilot was to gather information on both depressive symptoms and GP's' assessments of depressive mood in persons over 65 coming for a consultation in two general practices. To assess the prevalence of depressive symptomatology, 87 patients were asked to complete the Zung Self-Rating Depression Scale (ZSDS) and the Geriatric Depression Scale (GDS). Six patients were identified as having depressive symptoms on the ZSDS and seven on the GDS. Information on GP's' assessments of depressive mood was gathered by asking GP's to what extent they thought patients had been depressed recently. With regard to patients identified by the GP's as being mildly or severely depressed, the GP's answered additional questions on diagnostic and therapeutic approaches. The GP's identified eleven out of 87 patients as being mildly depressed, nobody was classified as being severely depressed. Five out of six patients with a ZSDS score of 50 and higher were not identified by the GP's as being mildly depressed. The prevalence of depressive symptoms based on ZSDS-scores was somewhat lower than expected (7.5%). PMID- 1926297 TI - [Physical symptoms of Parkinson's disease and the score on Beck's Depression Inventory]. AB - In patients with Parkinson's disease high prevalence of depression has been estimated. This prevalence may be overestimated since the commonly used assessment of depressive complaints neglects the correspondence with physical symptoms of Parkinson's disease and psychosomatic symptoms in depression. To evaluate the effect of this contamination, we presented a frequently used questionnaire for assessing depressive complaints, Beck's Depression Inventory (BDI), to eight neurologists specialized in Parkinson's disease. We asked them to select those items on which Parkinson patients might receive high scores merely because of the physical symptoms of their disease. Based on their consistent judgments, a BDI-version corrected for somatic items was constructed. Next, the scores of the original and the corrected version were computed for 27 outpatients with Parkinson's disease (from mild to very severe) and 52 psychiatric inpatients who were being treated for depression. Prevalence of depression were 74% (original BDI) and 48% (corrected BDI) for the Parkinson group and 75% and 81% respectively for the psychiatric group. Results indicate that great care should be taken in interpreting scores on depression inventories in patients with Parkinson's disease. In general, the results raise doubts on the validity of somatic complaints as indicators of depression in patients with Parkinson's disease. PMID- 1926298 TI - [Sleep problems and use of hypnotics in a nursing home. An inventory]. AB - An inventory has been made on sleeping problems and the use of hypnotics in a nursing home. Contrary to general opinion, the results show that admission to a nursing home does not have to lead to an increase of hypnotics and neuroleptics used. One third of the total patient population revealed severe subjective sleeping problems, for which, however, a therapeutic intervention was not always necessary. In particular somatic revalidation patients showed high percentages of sleeping complaints and medical treatment. A communication hypothesis is presented as a possible explanation: somatic patients are able to ask for medication contrary to psychogeriatric patients, for whom the caregiving network often initiates therapeutic intervention. Attention is focussed on a few sleep disturbing stimuli that often occur in the setting of a nursing home. Prevention of these stimuli implicates changes in the nursing care organization. PMID- 1926299 TI - [CAMDEX-N: the Dutch version of the Cambridge Examination for Mental Disorders of the Elderly with automatic data processing]. AB - In the study of dementia four distinct categories of instruments can be distinguished: instruments to examine cognitive dysfunction, to measure the severity of dementia, to assess disturbances in daily behaviour, and instruments to make a differential diagnosis of dementia. The Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), published in 1988, incorporates these four categories in a single comprehensive interview schedule. Items related to the diagnosis of clouded/delirious state, depression and other psychiatric symptoms are also included. The Dutch version (CAMDEX-N) and accompanying software for data analysis and for scientific research were developed. Items were added to the section on physical and neurological examination, and to the section on ancillary investigations. The software can be adapted to future developments in dementia research. PMID- 1926300 TI - Medicare reimbursement deficits: are nursing costs to blame? AB - Nursing costs were found to be only 11% of the total operating costs. This finding dispels the myth that nursing service is an expensive expenditure for hospitals. The range of facility cost compared with DRG reimbursement was wide, which points to the need to scrutinize costs other than nursing as the sources of hospital deficits. Nursing costs were found to be lower than facility or OR costs. Nurse managers need to emphasize this cost effectiveness to decrease the chance of staffing cuts and requests for concessions in wages or benefits for nurses. Nurse managers need to plan their financial activities to ensure their hospital cost is less than, or at most equal to, the DRG payment. PMID- 1926301 TI - Sciatica management: chemonucleolysis vs. surgical discectomy. AB - True sciatica, and the back pain associated with it, are symptoms stemming from a common anatomical lumbar distortion--compression of a spinal nerve root. Two therapeutic approaches have evolved: surgical laminectomy and discectomy for relief of compression of a lumbar nerve root; and chemonucleolysis, a tissue modification technique using the intradiscal injection of the proteolytic enzyme chymopapain. Chemonucleolysis has been demonstrated to have a successful outcome at the 75% level in 6 weeks and at the 80% level in 6 months. Lumbar microdiscectomy appears to be 85% effective at 3 months. PMID- 1926302 TI - Intrathecal morphine in younger patients for postoperative pain following spinal fusion. AB - Intrathecal morphine in an average dose of 0.01 mg/kg was given to 33 patients between ages 11 and 16 years who had spinal arthrodesis for idiopathic scoliosis. The morphine was administered intrathecally as a 10 cc bolus at the conclusion of the arthrodesis, but before closure. The goal was to study safety in terms of respiratory depression and pain relief. Respirations occurred spontaneously in 30 of the 33 patients within 15 minutes of cessation of anesthesia. Respiratory depression occurred in five patients, four of whom had arterial blood pCO2 levels greater than 60 mm Hg. Thirty-one patients had relief of pain for 8 to greater than 40 hours, averaging 18 hours. Two patients had no noticeable pain relief. There appeared to be no relation between dose and pain relief in this limited dose range. We were unable to duplicate the long duration of pain relief reported elsewhere. We also were unable to decrease the side effects of respiratory depression and nausea to a level reported by others. It may be that the 10 cc bolus injected intrathecally circulates to the brain and ventricles faster than desired, or that factors relating to type of anesthesia or dose need to be considered. Low-dose intrathecal morphine does provide noticeable pain relief in younger patients undergoing spinal fusion. The side effects of nausea and respiratory depression can be managed safely with medication. PMID- 1926303 TI - Harassment comes in assorted flavors. PMID- 1926304 TI - Fluid volume deficit related to active loss. PMID- 1926305 TI - Cleaning products may cause analytical equipment errors. PMID- 1926306 TI - Verbal abuse and sexual harassment in the OR. PMID- 1926307 TI - When women lead. AB - In participative management, it is the leader's role to involve employees and to create situations that contribute to positive feelings among employees about work. These techniques are based on the premise that individuals perform best when they feel good about themselves and their work. Women are more likely than men to motivate employees to turn self-interest into the goals of the organization. "Feminine" management characteristics include encouraging participation, sharing power and information, promoting selfworth of others, and energizing others. The feminine leadership style is especially relevant to and useful in nursing because it is a high-stress occupation. An interactive approach provides the necessary support that employees and colleagues need to survive in high-stress environments. PMID- 1926308 TI - Blood donation by the healthy elderly. PMID- 1926309 TI - Who should be our blood donors? PMID- 1926310 TI - A prospective study of blood donations in healthy elderly persons. AB - Iron stores were observed in 57 healthy elderly volunteers, between 63 and 77 years of age, who donated 5 units of blood over approximately 1 year. An equal number of nondonors who contributed approximately 7 mL of blood at each visit for iron status measurements only were seen at the same frequency as the donor population. At entrance to the study, iron stores in women and men averaged 724 and 875 mg, respectively. After five donations, mean iron stores dropped to 67 mg in women (n = 27) and 362 mg in men (n = 30); four women (15%) became iron deficient, while two (7%) developed iron deficiency anemia. Three men (10%) developed iron deficiency, but none were found to be anemic. Mean intakes of iron were 23.3 and 22.5 mg per day, respectively, for women and men. Iron intakes were adequate to meet iron requirements of nondonors, but they were not sufficient to halt the steady decrease in iron stores among the donor population, in whom iron absorption increased from approximately 5 percent at entrance to 14 percent at the time of the fifth donation. In summary, healthy elderly persons may contribute to the national blood resource; however, donations should probably be limited to less than five per year or donors should regularly take an iron supplement to preserve reasonable amounts of iron reserves. PMID- 1926311 TI - Characteristics of elderly blood donors. AB - The aging of our society will result in an increased demand for blood components, but it also has the potential to produce a large group of blood donors, the elderly. To study the effects of regular donation by older persons, a randomized, controlled trial is being conducted among 244 healthy, elderly volunteers. This report focuses on the efficacy of the recruiting efforts for that study and describes the resultant population in terms of their demographics, medical status, and donation safety. Of 325 potential subjects, 18 percent were disqualified and 7 percent refused entry into the study. After medical evaluation, only 2 persons were disqualified for conditions not detected by the usual blood services screening protocols. The resultant elderly donor population (n = 244) was well-educated, middle-income, and, for the most part, married. The group reported more past and present medical conditions, past surgical procedures, and current medications than would be expected in a younger donor group. Reactions to donation were infrequent and mild. With current screening and donation procedures, blood donation by the elderly appears to be safe and practical. PMID- 1926312 TI - Human immunodeficiency virus type 1-infected blood donors: epidemiologic, laboratory, and donation characteristics. The HIV Blood Donor Study Group. AB - Transmission of human immunodeficiency virus type 1 (HIV-1) by homologous blood transfusion in the United States (US) is minimized by the deferral of potential donors who are at risk for HIV-1 infection and by the screening of all donations for HIV-1 antibody. HIV-1-seropositive donors at 20 blood centers were studied for information to be used in evaluating the safety of the US blood supply and making recommendations to increase that safety. From June 1988 to August 1989, 829 (0.04%) of 2,192,000 donors were found to be seropositive; 512 were interviewed. Of 388 seropositive men, 56 percent had had sex with men, 10 percent had used drugs intravenously, 8 percent had had sex with intravenous drug users, and 27 percent had no identified risk. Of 124 seropositive women, 58 percent had had sex with men at risk for HIV (81% of whom used drugs intravenously), 5 percent had used drugs intravenously, and 41 percent had no identified risk. Racial and ethnic minorities made up 68 percent of seropositive donors (black, 38%; Hispanic, 30%) and approximately 14 percent of all donors. The 157 persons with no identified risk had demographic characteristics and serologic test results for syphilis and hepatitis B that were more similar to those of HIV-1 seropositive donors with recognized risk than to those of seronegative donors. Three health care worker-blood donors (from an estimated 93,100 health care worker-donors) had infection that was probably acquired occupationally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1926313 TI - Human immunodeficiency virus type 1-infected blood donors: behavioral characteristics and reasons for donation. The HIV Blood Donor Study Group. AB - Between May 1988 and September 1989, 829 human immunodeficiency virus type 1 (HIV 1)-seropositive donors were identified from 3,919,000 units of blood donated at 20 United States (US) blood centers. Of the 829,512 (62%) were interviewed to assess behavioral characteristics of the largest subgroup, men reporting sex with men, use of the confidential unit exclusion (CUE) and reasons for donation among all donors. Among 216 men reporting sex with men, 97 percent had male and 72 percent had female sexual contact since 1978. The majority identified themselves as bisexual (29%) or heterosexual (26%). Although 61 percent of 512 donors were aware of their risk behavior at donation, including 57 percent of those infected through heterosexual transmission, only 5 percent used the CUE. Reasons for donation included failure to read carefully (46%) or comprehend (15%) the deferral materials, pressure to donate (27%), a desire to be tested for HIV-1 (15%), and a reliance on screening to identify infected blood (10%). Reasons given for a perception of being at low risk included no recent risk behaviors, infrequent risk behaviors, or modification of risk behaviors. To reach high-risk donors, centers should assess whether referral materials provide necessary medical information and are clearly written for persons with diverse cultural and language backgrounds. Staff should be encouraged to avoid the use of culturally stigmatized terms and behaviors that may be perceived as high pressure. PMID- 1926314 TI - Effect of blood transfusion on survival in a mouse bacterial peritonitis model. AB - Allogeneic blood transfusions can result in alloimmunization or immunosuppression. A previous study demonstrated a deleterious effect of allogeneic blood transfusion on tumor growth in mice that was dependent, in part, on the dose of tumor cells with which the host animal was inoculated. The current study examined the effect of a similar allogeneic blood transfusion protocol on survival in a mouse bacterial peritonitis model. C57Bl/6J mice were transfused with 0.2 mL of heparinized fresh whole blood from C57Bl/6J (syngeneic) or Balb/c (allogeneic) mice. Transfusions were given on Days -10 and -7. On Day 0, mice were injected intraperitoneally with 10(7) Escherichia coli. Survival at Day 7 was 61 percent in the allogeneic blood transfusion group and 55 percent in the syngeneic blood transfusion group (p = 0.52). Experiments using different strains of mice, different transfusion protocols, and different doses of bacteria also failed to demonstrate an effect of allogeneic blood transfusion on survival. The results demonstrate that blood transfusion does not influence survival after a septic challenge with bacteria. The data obtained in the present study, together with those obtained in the tumor model, suggest that the mechanisms by which the allogeneic blood transfusion impedes host defense against bacterial infections is different from the mechanisms involved in tumor growth. PMID- 1926315 TI - Effects of blood transfusion on the immune responsiveness and survival of cancer patients: a prospective study. AB - To evaluate whether blood transfusion exerts an adverse influence on cancer evolution, a prospective clinical and immunologic investigation was carried out on 58 surgical patients with gastric or colorectal adenocarcinoma. None had had previous transfusion; 35 received perioperative transfusion. Among preoperative variables, only red cell count and hemoglobin concentration were significantly reduced in the patients transfused at operation. Other clinical characteristics and immunologic functions (except interferon-gamma release) did not differ significantly from those of untransfused patients. The survival rate of transfused patients, although shorter, was not significantly different from that of untransfused patients. Immunologic tests done after surgery on 30 patients (17 transfused and 13 untransfused) did not show significant differences in the two groups. Significant increases in interleukin-2-stimulated production and immunoglobulin M synthesis were observed in transfused patients after surgery. Patients transfused perioperatively with more than 3 units of blood had some evidence of decreased immune function, but differences were not significant. While shorter survival and some immunologic changes may correlate with the number of transfusions, more patients must be studied to determine whether this relationship will be confirmed. PMID- 1926316 TI - Safety of blood donations following a natural disaster. AB - To evaluate the relative safety of blood donations given in response to a major disaster, donor demographics and infectious disease test results were compared for donations made during the 10 days following the October 17, 1989, San Francisco Bay Area earthquake and those made during the preceding 6 months. These comparisons were made for donations given to the regional blood center in the area that was immediately affected by the disaster (Irwin Memorial Blood Centers) and for those given in an unaffected region (Los Angeles/Orange Counties Region, American Red Cross Blood Services). The rate of donation increased more than 200 percent during the 5 days following the earthquake in both the disaster-affected and unaffected regions. Both the disaster-affected and unaffected regions observed significant increases in the proportions of donations by first-time donors, by persons aged 20 to 39 years, and by women. The rates of confirmed positivity for infectious disease markers for post-earthquake donations did not differ significantly from rates for homologous donations given during the preceding 6 months, particularly when the rates were adjusted for the increased representation of first-time donors. Approximately 39 percent of post-earthquake first-time donors gave blood again within the following 6-month period. It is concluded that donations given after major disasters are essentially as safe as routine donations and that active efforts to recruit these donors again can be undertaken without reservation. PMID- 1926317 TI - Automated processing of human bone marrow can result in a population of mononuclear cells capable of achieving engraftment following transplantation. AB - A concentrate of mononuclear bone marrow cells is often desired for ex vivo treatment with pharmacologic agents, monoclonal antibodies, cytokines, and other agents prior to transplantation. A method has been developed for automated separation of mononuclear cells from large volumes of harvested bone marrow. A programmable instrument originally designed for clinical ex vivo cell separation and the plasma-pheresis of patients and blood donors was adapted to permit rapid preparation, in a closed sterile system, of a bone marrow product enriched with mononuclear cells. A mean (+/- SEM) of 53 +/- 30 percent of the original mononuclear cells was recovered in a volume of 125 +/- 42 mL containing 82 +/- 12 percent mononuclear cells. This technique removed 95 +/- 9 percent of the red cells in the original marrow. No density gradient materials or sedimenting agents were employed in this process. Of 36 marrows processed by this technique, 19 autologous (6 of which were purged with 4-hydroperoxycyclophosphamide) and 7 allogeneic marrows have been transplanted, with all evaluable patients achieving a neutrophil count of 0.5 x 10(9) per L in a mean (+/- SEM) of 21 +/- 6 days. PMID- 1926318 TI - Serologic distinction between human T-lymphotropic virus (HTLV) type I and HTLV type II. AB - In November 1988, the Food and Drug Administration approved reagents for serologic screening for human T-lymphotropic virus type I (HTLV-I) infection in blood donors and patients suspected of having HTLV-I-related illnesses. These reagents are able to detect HTLV type II (HTLV-II), a close relative of HTLV-I with no known pathologic effect. The distinction between the two forms of HTLV is important to the donor and to any recipient of blood containing HTLV. The application to sera from 38 seropositive blood donors and 2 recipients (37 "confirmed" positive and 3 indeterminate by Western blot) of two methods (Western blot and peptide enzyme immunoassay) for serologic distinction between HTLV-I and -II is described. These results were compared to those from polymerase chain reaction (PCR) analysis of HTLV proviral DNA obtained from donor peripheral blood mononuclear cells. The peptide enzyme immunoassay was found to be less sensitive than the Western blot, but completely concordant with PCR results when differential reactivity could be established. The Western blot pattern showed complete diagnostic concordance with the samples with confirmed-positive serologic tests, but was incorrect in two HTLV-II-infected donors with indeterminate serologic tests. Thirty-three (89%) of the 37 individuals from this predominantly Native American and Hispanic group of blood donors were found to have HTLV-II. These findings confirm and extend previous reports that HTLV-I infection may be less common, and HTLV-II infection more common, than previously believed. The peptide enzyme immunoassay can provide most individuals who have positive results with the HTLV-I/II screening test with serologic distinction between HTLV-I and HTLV-II. PMID- 1926319 TI - The neonatal immune response to washed and irradiated red cells: lack of evidence of lymphocyte activation. AB - A total of 21 neonatal infants (11 males and 10 females) were evaluated for lymphocyte subpopulation changes and cellular activation following the receipt of washed and gamma-irradiated red cells. The mean donor exposure was 2 +/- 1.5 donors, and the mean white cell concentration of each 10-mL-per-kg transfusion was 2 x 10(7) cells. A total of 2800 rad (28 Gy) was delivered to each red cell unit prior to washing. The lymphocyte subsets CD3+, CD4+, CD8+, CD19+, CD3+/CD25+, CD3+/HLA-DR, CD4+/CD45RA, CD4+/CDw29, and CD4+/ICHL-1 were analyzed, as were plasma gamma-interferon and neopterin levels, before and after blood transfusion. Posttransfusion samples were obtained from 3 to 12 days after the last blood transfusion. There were no posttransfusion changes in the percentage of lymphocyte subsets analyzed. Furthermore, overlay-histogram analysis of pretransfusion and posttransfusion CD45RA-, CDw29-, and UCHL-1-positive helper T cells failed to reveal a shift in mean channel fluorescence intensity, which is indicative of a lack of cellular activation. Gamma-interferon levels remained unchanged after transfusion (range, 90 +/- 5.9 to 95.5 +/- 5.3 pg/mL), as did neopterin levels (range, 3.7 +/- 1.5 to 4.6 +/- 1.5 ng/mL). This study could not find any evidence, by either cellular or humoral markers, of the activation of neonatal lymphocytes by transfusion. It is hypothesized that this failure to observe lymphocyte activation is due to the low number of donor white cells present in washed, irradiated red cells and/or to a lack of recipient recognition of transfused, allogeneic, donor white cells. PMID- 1926320 TI - Reducing white cells in platelet units. AB - White cells (WBCs) constitute a significant contaminant of platelet concentrates (PCs). Various technologies, including apheresis and filtration, are currently being developed to minimize the carryover of WBCs into platelets. The aim is to reduce contamination of less than 10(8) WBCs per platelet unit. As part of quality control monitoring of the blood bank operations, the centrifugation protocols employed in the preparation of platelet-rich plasma (PRP) have been evaluated for their impact on the WBC content of the PCs. The WBC content, which is expressed throughout the PRP volume as well as in the PC, reflects the degree of braking. For example, after centrifugation (2500 rpm, 4 min) of whole blood into packed red cells (RBCs) and PRP, braking-induced mixing increases the WBC content of the expressed PRP. Variations in the braking rates of the centrifuges used also correlate with the WBC carryover into packed platelets. An alternative centrifugation protocol to minimize WBC carryover is suggested. Whole blood is centrifuged at 2500 rpm for 1.5 minutes (rather than 4 min) and allowed to stop with no braking. This procedure adds some 3 minutes to the total centrifugation time, but the relative integral of this centrifugation program is approximately 50 percent smaller than that of the normally employed centrifugation protocol (with braking). It was observed that the WBC content throughout the expressed PRP, or in the entire PC, is reduced by about 75 percent. These results show that an effective method of significantly decreasing the WBC content of platelet units is simply to prepare PRP with reduced centrifugation time and with the braking programs disengaged. PMID- 1926321 TI - Virucidal levels of ozone induce hemolysis and hemoglobin degradation. AB - The animal virus, vesicular stomatitis virus (VSV), and the bacterial virus, phi 6, were inactivated by greater than 4 log10 in response to incubation with 13 to 14 mL of 1.4 mmol per L (65 micrograms/mL) to 1.6 mmol per L (75 micrograms/mL) of overlaid ozone in virus-spiked, dilute, red cell suspensions. Virus inactivation was greatly inhibited when ozone was overlaid in the presence of high-hematocrit red cells or, to a lesser degree, high levels of plasma. At hematocrits at which 5 to 6 log10 of VSV were inactivated, ozone caused 30 percent hemolysis, as measured by the loss of total cellular hemoglobin. Unexpectedly, this level of hemolysis could not be observed in supernatants because of the ozone-induced destruction (bleaching) of extracellular hemoglobin. These results suggest that ozone may have little biological specificity for damaging viruses over red cells. PMID- 1926322 TI - Captopril-enhanced binding of PlA1 (HPA-1a) antibodies in posttransfusion purpura. AB - A case of posttransfusion purpura is reported in a 90-year-old patient whose PlA1 antibody (anti-HPA-1a) was found to bind better to HPA-1a in the presence of captopril, a drug the patient had taken. Initially, IgG antibodies were found in the serum that reacted with normal platelets, but the binding of the antibody was increased in vitro by captopril, which suggested that captopril was responsible for the thrombocytopenia. However, in vitro studies demonstrated that the patient's platelets were negative for HPA-1a and that anti-HPA-1a was present in the serum, both of which findings were consistent with the diagnosis of posttransfusion purpura. The binding of this antibody was enhanced 50 percent by captopril in vitro, and increased binding in the presence of captopril did not occur when the anti-HPA-1a was removed. Similar results were obtained with serum containing anti-HPA-1a from another patient with posttransfusion purpura. Thus, captopril may increase the binding of anti-HPA-1a and confuse the determination of the cause of acute thrombocytopenia. PMID- 1926323 TI - An auto-anti-M causing hemolysis in vitro. AB - A 64-year-old white man, who had never received a transfusion, was found to have anti-M in his serum. The antibody agglutinated all M+ red cells in room temperature tests. When the ionic strength of the test milieu was reduced by use of an additive solution and the tests were incubated at 37 degrees C, the antibody hemolyzed M + N- but not M+N+ red cells. All M+ red cells reacted in indirect antiglobulin tests using polyspecific antiglobulin reagents when such tests followed an initial incubation at room temperature. When red cells and the patient's serum were warmed to 37 degrees C before being mixed, no antibody activity was demonstrable. The antibody was adsorbed to exhaustion onto M+N- and M+N+ red cells (including the patient's own), and its activity was destroyed by dithiothreitol. There was no evidence of in vivo red cell destruction by the autoantibody. No previously reported example of anti-M has been shown to activate complement in conventional in vitro tests. This example was extraordinary in that it caused sufficient complement activation to present as an in vitro hemolysin. PMID- 1926324 TI - Rh33 in two of three German siblings with D+ C+ c+ E- e+ red cells. AB - The proposita in a German family of three siblings has D+ C+ c+ E- e+ f+ Rh: 17,19,33,34 red cells with weak C, e, f, Rh19, and Rh34 and stronger-than-usual Rh33 expression. One sibling has D+ C+ c+ E- e+ f+ Rh:17,19,33,34 red cells with weak f and ordinary-strength Rh33, and the other sibling has D+ C+ c+ E- e+ f+ Rh:17,19,-33,34 red cells. In the absence of any further family members, the proposita's unusual phenotype suggests that she has an RoHar haplotype and a "new" Rh haplotype, provisionally named R1Lisa, that encodes Rh33, normal strength D, weak C, weak or nondemonstrable e, Rh19, and Rh34, but not Rh17. Her Rh:33 sibling may have R1 and RoHar and her Rh:-33 sibling R1 and r haplotypes. PMID- 1926325 TI - Risk factors in hepatitis C virus-infected blood donors. AB - Risk factors of parenteral and nonparenteral exposure to hepatitis C virus (HCV) infection were studied in 125 blood donors in The Netherlands who were positive for anti-HCV on enzyme-linked immunosorbent assay (ELISA). Risk factors were related to confirmatory test results of four-antigen recombinant immunoblot assay (4-RIBA) and polymerase chain reaction (PCR) of the HCV 5' untranslated region. Twelve (10%) of the 125 anti-HCV C100 ELISA-positive blood donors were 4-RIBA positive. Eleven (92%) of 12 4-RIBA-positive blood donors were PCR positive, and all 113 remaining 4-RIBA-negative or -indeterminate donors were PCR negative. Eleven (92%) of 12 4-RIBA-positive blood donors had a risk factor of parenteral exposure, as compared to 17 (15%) of 113 4-RIBA-negative or -indeterminate donors. The prevalence of confirmed HCV infection among Amsterdam blood donors is calculated at 0.04 percent; parenteral exposure appears to be the major risk factor for HCV infection. PMID- 1926326 TI - Partial D antigens disclosed by a monoclonal anti-D in Japanese blood donors. PMID- 1926327 TI - Survival studies with another example of anti-Cr. PMID- 1926328 TI - Anti-Wr(a) and mild hemolytic disease of the newborn. PMID- 1926329 TI - American Association of Blood Banks, 44th annual meeting. November 9-14, 1991. Abstracts. PMID- 1926330 TI - Long-range interactions in proteins. PMID- 1926331 TI - Photosynthetic reaction centres: variations on a common structural theme? AB - From their hybrid properties, the reaction centres of green sulphur bacteria and heliobacteria seem to be the missing links between the two branches of the reaction centre family, typified by higher plant photosystem I and the purple bacterial reaction centre. This suggests that all of the diverse types of photosynthetic reaction centres have closer structural resemblances than was previously thought. PMID- 1926333 TI - Biochemistry: the Israeli dilemmas. PMID- 1926332 TI - Arginyl-glycyl-aspartic acid (RGD): a cell adhesion motif. AB - The tripeptide Arg-Gly-Asp (RGD) was originally identified as the sequence within fibronectin that mediates cell attachment. The RGD motif has now been found in numerous other proteins and supports cell adhesion in many, but not all, of these. The integrins, a family of cell-surface proteins, act as receptors for cell adhesion molecules. A subset of the integrins recognize the RGD motif within their ligands, the binding of which mediates both cell-substratum and cell-cell interactions. RGD peptides and mimetics, in addition to providing insights into the fundamental mechanisms of cell adhesion, are potential therapeutic agents for the treatment of diseases such as thrombosis and cancer. PMID- 1926334 TI - Acidic macromolecules of mineralized tissues: the controllers of crystal formation. AB - The deposition of minerals within many biological tissues is a controlled process. Among the most active agents that control biological mineralization are a group of unusually acidic proteins and glycoproteins. These can interact specifically with some crystal faces but not others, induce oriented nucleation, or intercalate in a regular manner into the crystal lattice itself. PMID- 1926335 TI - Neuronal polarity: targeting of microtubule components into axons and dendrites. AB - The functional polarity of nerve cells depends on the outgrowth of both axons and dendrites. These processes, which were distinguished by morphological and physiological criteria, have been shown in recent years to differ in molecular composition, including their cytoskeleton. The asymmetric distribution of cytoskeletal elements and, particularly, the segregation of microtubule associated proteins by their differential transport, may play an important role in the assembly of distinct microtubules in the two neuronal domains. An additional mechanism to achieve this subcellular localization is the transport of specific mRNAs to allow the local synthesis of specific proteins close to their functional site. This may endow the cell with a rapid mechanism for the regulation of synthesis under special conditions, which may be important during neuronal development and plasticity. PMID- 1926337 TI - CD4 monoclonal antibodies in organ transplantation--a review of progress. PMID- 1926336 TI - Extracellular sequestration and release of fibroblast growth factor: a regulatory mechanism? AB - Basic fibroblast growth factor, (bFGF), promotes the formation of new blood capillaries and is sequestered and protected by binding to heparan sulfate (HS), both on the cell surface and in the extracellular matrix. Release of HS-bound bFGF by heparin-like molecules and HS-degrading enzymes (i.e., heparanase) provides a novel mechanism for regulation of the growth of capillary blood vessels in normal and pathological situations. The extracellular matrix also serves as a storage depot for other growth factors and enzymes. PMID- 1926338 TI - Factors determining prolongation of rat heart allograft survival by perioperative injection of donor spleen cells. AB - Previously, we have shown that a perioperative injection of donor mononuclear cells in combination with cyclosporine treatment on day 2 after transplantation prolongs heart allograft survival in rats. In this study we determined whether the efficacy of this treatment was influenced by the same factors that have been shown to affect the efficacy of preoperative administration of donor cells. The effect of the following factors were investigated: dosage and repetition of the donor cell injection, viability of the donor cells, immunosuppressive drugs other than cyclosporine, and the rat strain combination. We found that there was an optimal dosage of donor cells; dosages of 4 x 10(7) or 1 x 10(8) cells gave the best heart graft survival. Repetition of the donor cell injection was not useful. Reducing viability of the cells by irradiation did not abrogate the prolonged graft survival, whereas killing of the cells did. Methylprednisolone, azathioprine, or cyclophosphamide in combination with the perioperative donor cell injection did not prolong heart graft survival in comparison with treatment with the drug only. The efficacy of this treatment was also influenced by the rat strain combination. In some combinations, this treatment prolonged graft survival, whereas in others an effect was absent or undetectable. Importantly, this treatment never adversely affected graft survival. We conclude that the efficacy of this treatment is influenced by similar factors as found for preoperative treatment with donor cells. A major advantage of this treatment over preoperative blood transfusions is that it avoids sensitization. PMID- 1926340 TI - The effects of pretransplant cyclosporine therapy on rats grafted with twelve hour cold-stored livers--with special reference to reperfusion injury. AB - The effect of pretreatment with cyclosporine on liver preservation was studied using a rat liver transplant model. In a preliminary 1-week survival study, 59 liver transplants were performed. In group A, neither donors nor recipients were treated. In group B, the recipients were pretreated by a 3-day course of CsA (10 mg/kg/day p.o.), but the donors were untreated. In group C, the donor rats were pretreated for 3 days with the same doses of CsA as in group B, but the recipients were not treated. The donor livers in each group were stored for 12 hr at 4 degrees C with Eurocollins solution and transplanted to the recipients. The CsA pretreatment to recipients (group B) significantly improved 1-week survival (57.1%, 8/14, P less than 0.01 versus control group A; 0%, 0/14 or group C; 14.3%, 2/14). To study lipid peroxidation and morphology, 72 rat livers were studied in 9 groups. In summary, CsA pretreatment to recipients resulted in suppression of the increase in MDA levels and amelioration of endothelial injury after transplantation. On the other hand, donor pretreatment exerted dual effects on the grafts; it ameliorated endothelial injury after reperfusion, but its hepatotoxic action exacerbated hepatocellular damage during hypothermic storage. Our study suggests that CsA pretreatment, particularly to recipients, is beneficial in liver preservation for hepatic transplantation. The mechanisms are discussed with regard to ischemia/reperfusion injury to hepatic endothelium. PMID- 1926339 TI - Protection of rat heart from damage due to ischemia-reperfusion during procurement and grafting by defibrotide. AB - We studied the efficacy of defibrotide, a prostacyclin-stimulating agent, in preventing ischemia reperfusion injury in Wistar rat heart by using three experimental models: (1) hearts from donors were perfused with the drug (32 mg/kg/hr) during 15, 30, 45, and 60 min of cold ischemia following 5, 10, and 15 min of warm ischemia; (2) hearts from donors treated with the drug were cold stored for 12 or 24 hr; and (3) procured hearts perfused with the drug were isografted, after 30 or 60 min of warm ischemia, in recipient rats treated daily with defibrotide. Hearts perfused with saline and/or vehicle of the drug were used as controls. At the end of established ischemia times, and after 30 min, and 2, 4, 7 and 14 days from transplantation, hearts were rapidly cooled in liquid nitrogen. ATP, ADP, AMP, cAMP contents, and NAD+/NADH ratios were evaluated in prepared tissue extracts. Cardiac ATP and ADP levels and NAD+/NADH ratios were significantly higher in defibrotide-treated organs than in controls. Isografted defibrotide-treated hearts were also significantly preserved, with respect to controls, from the loss of ATP levels until rejection occurred. Our results demonstrate the protective activity of the drug against the myocardial metabolic damage due to ischemia-reperfusion. PMID- 1926341 TI - Urinary levels of activated trypsin in whole-organ pancreas transplant patients with duodenocystostomies. AB - Urinary levels of trypsinogen and active trypsin were measured in 34 urine samples from 14 patients an average of 23 months following whole organ pancreas transplantation and duodenocystostomy. Timed urine specimens obtained 30 min and 90 min following a time zero void were collected from 5 patients in an effort to define the kinetics of trypsinogen secretion and activation. Total urinary protein and urinary pH were correlated with urinary levels of trypsin and trypsinogen. Twenty-one specimens from 8 normal volunteers and a single specimen from a pancreas transplant patient with a duodenoenterostomy served as controls. Activated trypsin was present in 33 of 34 specimens from 13 of the 14 transplant patients. The average total trypsin activity in all samples was 84.4 micrograms/ml urine (+/- SE 9.6). Trypsinogen was present in 13 of 34 samples, from 7 of 14 patients. The average trypsinogen concentration of all 34 samples was 9.6 +/- 6.2 micrograms/ml. No trypsin or trypsinogen activity was identified in any control sample. In the 5 patients undergoing timed urine collections total trypsin increased an average of 1.3-fold at 30 min and 1.1-fold at 90 min relative to time zero. Urinary trypsinogen increased an average of 7.1-fold at 30 min and 3.1-fold at 90 min following the initial void. Urinary pH and total urinary protein failed to show a significant correlation with urinary levels of total trypsin or trypsinogen. These data suggest that trypsinogen is rapidly converted to active trypsin following secretion into the bladder, resulting in the high urinary trypsin levels that were detected in the majority of patients. PMID- 1926342 TI - Pharmacologic purging of malignant T cells from human bone marrow using 9-beta-D arabinofuranosylguanine. AB - Arabinosylguanine (araG) is a nucleoside analog that is rapidly converted by cells of the T lymphoid lineage to its corresponding arabinosylguanine nucleotide triphosphate, resulting in inhibition of DNA synthesis and selective in vitro toxicity to T lymphoblastoid cell lines as well as to freshly isolated leukemia cells from patients with T cell acute lymphoblastic leukemia. In this report, we demonstrate that araG is an effective agent to use for chemoseparation of malignant T lymphoblasts from human bone marrow. When freshly isolated human T leukemia cells or T lymphoblastoid cells were treated with 100 microM araG for 18 hr, up to 6 logs of clonogenic T cells could be eliminated without appreciable toxicity to the normal myeloid, erythroid, and megakaryocytoid clonal progenitor cells. We discuss the use of this agent in ex vivo elimination of residual malignant T cells from marrow of patients requiring myeloablative chemotherapy with autologous bone marrow rescue. PMID- 1926343 TI - Improved outcome of cadaveric renal transplantation due to calcium channel blockers. AB - Calcium channel blockers (CCB) administered to recipients of cadaveric renal transplants have been shown to improve graft function, decrease the incidence of delayed function, prevent acute cyclosporine toxicity, and lessen the number of rejection episodes in the first several weeks posttransplant. In order to determine whether CCB provide a similar long-term benefit, a retrospective analysis of 83 first cadaveric renal transplants performed in 1987 and 1988 was performed. The clinical course of 17 patients who were discharged and maintained on CCB therapy for 1 year was compared with that of 24 patients who never received CCB during the same 1-year period. The remaining 42 patients were excluded for failing to meet these inclusion criteria. The two groups were similar with respect to age, sex, cold ischemia time, degree of sensitization, HLA matching, DR matching, and DR mismatching. The no CCB group did receive a significantly greater number of pretransplant transfusions. In the 1 year of follow-up, graft loss in the CCB group was less than in the no CCB group (1/17, 5.9% vs. 6/24, 25%). There was a striking decrease in the percentage of first rejection episodes in the CCB group as compared with no CCB therapy (35% vs. 83%, P less than 0.005). In addition, a similar decrease in second rejection episodes was found in the CCB group (18% vs. 33%, P less than 0.05). The two groups also were compared with respect to graft function. Despite similar serum creatinine levels at 1 month (CCB 1.8 mg% vs. no CCB 2.2 mg%, P = 0.37) and 1 year (CCB 1.7 mg% vs. no CCB 2.4 mg%, P = 0.19), the CCB group had a significantly higher glomerular filtration rate at 1 month (53.9 vs. 38.7, P less than 0.05) and 1 year (57.0 vs. 35.0, P less than 0.001) as measured by clearance of radiolabeled iothalamate. These results suggest that the short-term improvements noted in both graft function and rejection episodes with CCB are maintained for the first year posttransplant. More importantly, CCB use results in improved 1-year graft survival. PMID- 1926344 TI - Chronic liver dysfunction in heart transplant recipients, with special reference to viral B, C, and non-A, non-B, non-C hepatitis. A retrospective study in 80 patients with follow-up of 60 months. AB - In order to assess the prevalence, causes, and severity of chronic liver dysfunction (LD) in heart transplant patients, 80 transplanted patients followed for 60 months (median; range, 1.5-98 months) were reviewed. Sustained liver dysfunction was found in 50 patients, occurring during the first year after heart transplantation in 42 (84%) of them. Most patients were asymptomatic (80%). Causes for the liver dysfunction included non-A, non-B hepatitis in 16 cases (32%), viral B hepatitis in 13 (26%), delta hepatitis in one (2%), drug-induced hepatitis in six (12%), and cardiac failure in seven (14%). Anti-HCV antibodies were found in 56.2% of patients with non-A, non-B hepatitis and in 22% of patients with HBV hepatitis. It was found neither in patients with drug-induced hepatitis cardiac failure nor in patients with normal liver tests. This study outlines a high prevalence of LD (62.5%) in heart transplant patients, the high frequency of viral-related chronic LD (usually of moderate severity), and high incidence of HCV and HBV hepatitis. PMID- 1926345 TI - Discodermolide--a new, marine-derived immunosuppressive compound. II. In vivo studies. AB - The in vivo immunosuppressive properties of a novel, marine-derived compound, discodermolide, are reported here. Discodermolide was effective in suppressing the graft-versus-host splenomegaly response of BALB/c----CB6F1 (BALB/c X C57BL/6J)F1 grafted mice at 5.0, 2.5, and 1.25 mg/kg, when administered as daily, i.p. injections, for 7 days. Mice treated with 5.0 and 2.5 mg/kg demonstrated a high degree of suppression (219 and 150%, respectively); however, these dosages were associated with some degree of morbidity (2/5 and 4/5 survivors for 5.0 and 2.5 mg/kg, respectively). Mice that were treated with 1.25, 0.625, and 0.313 mg/kg remained healthy after a 7-day regimen, and continued to demonstrate suppression of splenomegaly (106%, 72%, and 76% suppression, respectively). Splenocytes obtained from discodermolide-treated, allogeneic grafted mice were suppressed in their ability to respond in vitro to optimal mitogenic concentrations of concanavalin A, and natural-killer-cell activity directed against YAC-1 tumor cells, compared with vehicle-treated, allogeneic grafted control mice. Lower dosages (2.5 and 1.25 mg/kg) of discodermolide, however, did not affect the subsequent ability of splenocytes obtained from these mice to produce IL-2 following in vitro stimulation with Con A. This was observed to be in contrast to the immunosuppressive activity observed with cyclosporine treatment of mice (150 mg/kg) for the ex vivo suppression of splenocyte production of IL-2. Treatment of normal, nongrafted mice with similar high dosages of discodermolide (5.0 mg/kg) for 4 days did not affect the primary antibody response of mice immunized with sheep red blood cells as measured by hemagglutination activity of their serum. These results suggest that discodermolide's in vivo immunosuppressive action appears not to be that of a generalized immunosuppressive agent and that its specific in vivo mechanism of action warrants further preclinical evaluation. PMID- 1926346 TI - Major-histocompatibility-complex restricted and nonrestricted autoimmune effector mechanisms in BB rats. AB - To investigate whether the immunologic mechanisms of autoimmune pancreatic beta cell destruction are MHC restricted, we examined the relative vulnerability of islet allografts from a panel of MHC-compatible and -incompatible donors to autoimmune damage after transplantation to spontaneously diabetic BB recipients. To circumvent a potentially confounding allograft response to the foreign islet graft, we utilized two strategies: (1) pretransplant in vitro culture of islets to delete intraislet APCs; and (2) induction of islet donor-specific immunologic tolerance in diabetes-prone BB rats. Experiments employing organ culture to prevent rejection demonstrated that MHC-incompatible grafts were significantly less vulnerable to autoimmunity than MHC-compatible grafts. In contrast, when we used the model of immunologic tolerance to exclude rejection, both MHC-compatible and -incompatible islet grafts were equally susceptible to autoimmune damage. The reason for this discrepancy has not been defined fully but may be related to our observation that tolerant BB animals exhibit increased peripheral blood NK-cell activity. NK cells are known to be cytotoxic to islets in vitro and could play a role in a non-MHC-restricted diabetogenic response in vivo. We conclude that both MHC-restricted and nonrestricted mechanisms are capable of contributing to anti beta-cell autoimmunity in BB rats. PMID- 1926348 TI - Recovery of monocytes after bone marrow transplantation--rapid reappearance of tumor necrosis factor alpha and interleukin 6 production. AB - After bone marrow transplantation many T-lymphocyte functions, including the production of cytokines (CK), such as interleukin 2, are severely depressed for months. The monocyte-derived cytokines tumor necrosis factor alpha and interleukin 6 are molecules central to immune functions. Moreover, they may be involved in graft-versus-host disease and in graft-versus-leukemia reaction. Hence, we have studied the reappearance of these CKs after BMT by analyzing whole blood cultures stimulated in vitro with lipopolysaccharide for 6 hr, followed by testing for the secretion of TNF in the WEHI 164/actinomycin D cytotoxicity bioassay and for IL-6 in the 7 TD 1 proliferation assay. We performed sequential studies in 6 children who were transplanted for aplastic anemia or leukemia with allogeneic bone marrow. We found that the production of both CKs can be induced as early as 10-14 days post BMT at the very beginning of engraftment, indicating that the regenerating monocyte system is recovering rapidly after BMT. Depletion and neutralization experiments confirmed that monocytes are the cellular source of the LPS-induced CK secretion after BMT. Control levels were reached 3 to 4 weeks post BMT. When analyzing the endotoxin-induced CK production in a larger panel of BMT patients after complete reconstitution, we could not detect any impact of acute or chronic GvHD, or of allogeneic or autologous BMT, nor did treatment with cyclosporine A (CsA) show any suppressive effect. Thus, our data show that the CK production of the monocyte/macrophage lineage is quite resistant to factors that do influence other cell lineages of the immune system during BMT. The coincident appearance of monocyte-derived cytokines and of GvHD suggests a role for these cytokines in GvHD in man. PMID- 1926347 TI - Prevention of syngeneic graft-versus-host disease by recovery of thymic microenvironment after cyclosporine. AB - Following a course of cyclosporine, syngeneic rat radiation chimeras consistently develop a GVHD-like syndrome. Correlation of the thymic immunopathology with conditions leading to syngeneic graft-versus-host disease (sGVHD) suggested the hypothesis that reconstitution of the normal thymic microenvironment after CsA is necessary for self-tolerance. When thymic regeneration is impaired, as in rats receiving previous mediastinal irradiation, then self-reactive effector cells are not regulated and proceed to damage the target tissues. Alternately, it could be argued that the observed thymic abnormalities are irrelevant to sGVHD. To test the primary hypothesis, post-CsA thymic reconstitution was prevented by total thymectomy in unirradiated rats. These rats consistently developed acute type sGVHD seen at 7 and 21 days post-CsA while rats from the CsA-treated sham thymectomy control group failed to develop sGVHD. Because thymectomy prior to CsA blocks sGVHD, most likely the peripheral effector cells in the post-CsA thymectomy group were derived from the CsA-altered thymus. The absence of sGVHD in the sham group indicates that the thymus led to active regulation of these cells after stopping CsA. If regeneration of the thymus restored only negative selection, then the sham thymectomy group should have also developed sGVHD. Flow cytometry and morphology of the spleen and lymph nodes demonstrated that the thymectomized rats, like CsA-treated radiation chimeras, experienced a significant delay in maturation of T cells following CsA. In contrast to the usual model in radiation chimeras, however, the post-CsA thymectomized rats did not convert to chronic type sGVHD. The importance of an abnormal thymus for this transition was confirmed in syngeneic radiation chimeras. Thymectomy after CsA in these rats also blocked the rapid transition to chronic sGVHD. PMID- 1926349 TI - Polyreactivity and antigen specificity of human xenoreactive monoclonal and serum natural antibodies. AB - Naturally occurring antibodies that react with xenogeneic antigens are a clinically important subset of antibodies because they initiate hyperacute rejection of organs transplanted between disparate species. This currently precludes the use of nonprimate organs for human transplantation. Most antibodies that arise after immunization are monoreactive, i.e., bind only to the immunogen. Similarly, some "natural" antibodies, e.g., isohemagglutinins, bind in a monoreactive manner. In contrast, other natural antibodies, e.g., those that bind to actin, are polyreactive (i.e., bind to multiple ligands). Such polyreactive antibodies may be derived predominantly from CD5+ B cells. In this study, we demonstrate that the majority of xenoreactive natural antibodies in human serum are polyreactive, as indicated by the ability of ssDNA and thyroglobulin (ligands commonly used as targets of polyreactive antibodies) to block the binding of the antibodies to xenogeneic antigens, whereas these ligands could not block the binding of antitetanus antibodies to tetanus toxoid. Furthermore, we compared the ability of 8 polyreactive and 7 monoreactive human mAb to bind to porcine antigens. All of the polyreactive mAb reacted with porcine antigens at mAb concentrations less than 3 micrograms/ml, while none of the monoreactive mAb reacted at concentrations less than 3 micrograms/ml. Each polyreactive mAb reacted with partially overlapping, but distinct sets of porcine cell surface moieties. These results indicate that human polyreactive mAb can bind to multiple xenogeneic antigens in a selective manner and that xenoreactive natural antibodies in human serum are largely polyreactive. PMID- 1926350 TI - The effect of cyclosporine on agonist-stimulated glomerular and mesangial cell vasodilatory prostaglandin production. AB - Cyclosporine A administration produces an increase in renal vascular resistance and a decrease in glomerular filtration rate in both human and animal models. CsA usage in humans has also been shown to alter the ability of the kidney to adapt to alterations in renal hemodynamics. CsA alters the production of prostaglandins by isolated rat glomeruli. Normally, vasoconstrictive agents stimulate the production of vasodilatory glomerular and mesangial cell PG. To determine if CsA alters glomerular and mesangial cell (MC) vasodilatory PG production in response to vasoconstrictive agents, we administered CsA, 20 mg/kg, or vehicle to rats for 7 days, or incubated mesangial cells with CsA 1 mcg/ml for 24 hr. Ex vivo glomerular PGE2 and 6-keto-PGF1a production was determined in the presence or absence of angiotensin II 10(-6) M and norepinephrine 10(-5)M. CsA administration decreased glomerular production of both eicosanoids in the basal and stimulated state. Incubation of MC with CsA markedly suppressed PGE2 and 6-keto-PGF1a production in response to stimulation with 200 nM angiotensin II. To determine if CsA inhibits angiotensin II-stimulated PG production prior to protein kinase C, we incubated glomeruli and MC with the diacylglycerol mimetic OAG. CsA depressed OAG-stimulated glomerular and MC PGE2 and 6-keto-PGF1a production. Conversely, CsA stimulated the production of PGE2 by renal medullary slices. We conclude that CsA blunts the vasoconstrictor-induced increase in glomerular and mesangial cell vasodilatory PG production, thereby removing a compensatory mechanism that maintains GFR in states of vasoconstrictor excess. PMID- 1926351 TI - Splenic artery aneurysms occurring in liver transplant recipients. PMID- 1926352 TI - Isolated splenic vein thrombosis as a cause of massive upper-gastrointestinal bleeding following orthotopic liver transplantation. PMID- 1926353 TI - Bile compositional changes and cholesterol stone formation following orthotopic liver transplantation. PMID- 1926354 TI - The need for venovenous bypass in orthotopic liver transplantation. PMID- 1926355 TI - Treatment of late allograft pancreatitis with oral pancreatic extract. PMID- 1926356 TI - Posttransplant lymphoproliferative disease of the liver successfully treated by retransplantation. PMID- 1926357 TI - Absence of tumor transmission from a cadaveric renal donor with malignant astrocytoma and a ventriculoperitoneal shunt--two-year recipient follow-up and review of the literature. PMID- 1926359 TI - A serologically unidentified HLA-B antigen detected by 1D-IEF in a cadaver kidney donor following a positive crossmatch. PMID- 1926358 TI - Complete remission and possible immune tolerance after multidrug combination chemotherapy for cyclosporine-related lymphoma in a renal transplant recipient with acute pancreatitis. PMID- 1926360 TI - The pathophysiologic role of endothelin in acute vascular rejection after renal transplantation. PMID- 1926361 TI - The high failure rate of OKT3 in the treatment of acute renal allograft rejection resistant to steroids with or without antithymocyte globulin. PMID- 1926363 TI - Immunohistochemical characterization of infiltrating macrophages in rejecting liver allografts in the rat. PMID- 1926362 TI - Evidence that canine pancreatic islets promote the survival of human hepatocytes in nude mice. PMID- 1926364 TI - Optimal concentration of additional albumin in the preserved solution of isolated donor heart. PMID- 1926365 TI - Identification of macrophages in vessel allograft atherosclerosis. PMID- 1926367 TI - Results of combined hepatic, pancreaticoduodenal, and renal procurements. PMID- 1926368 TI - Separate extraction of cardiac and pulmonary grafts for left single lung transplantation. PMID- 1926366 TI - Multiple organ procurement--a simple and safe procedure. PMID- 1926369 TI - Improved utilization of cadaver kidneys and living related donors. PMID- 1926370 TI - Reduced delayed graft function (DGF) after cadaveric kidney transplantation (CKT) with selective OKT3 induction and aggressive intraoperative management. PMID- 1926371 TI - Imported hepatic allografts: use of commercial airlines for transport. PMID- 1926372 TI - Refinements in cadaveric pancreas-kidney procurement and preservation. PMID- 1926373 TI - Multiple organ procurement--8 year experience. PMID- 1926374 TI - Multiple organ procurement for transplantation: the effect of peritoneal cooling. PMID- 1926375 TI - A modified technique for rapid combined heart, pancreas and kidney harvesting. PMID- 1926376 TI - Bench surgery in renal transplantation. PMID- 1926377 TI - Bench surgery for multiple renal arteries in kidney transplantation from living donor. PMID- 1926378 TI - Technique of experimental single lung transplantation. PMID- 1926379 TI - Mitochondrial injury in liver preservation is due to free fatty acids. PMID- 1926380 TI - Current status of the HTK solution of Bretschneider in organ preservation. PMID- 1926381 TI - Improved immediate renal allograft function following aggressive donor management and perfusion with UW solution. PMID- 1926382 TI - Addition of reduced glutathione to UW solution: clinical impact in liver transplantation. PMID- 1926383 TI - Effect of heart preservation on mitochondrial function. PMID- 1926384 TI - Small bowel transplantation in seven children: preservation technique. PMID- 1926385 TI - Favorable effects of dietary fish oil on capillary perfusion homogeneity after ischemia and reperfusion. PMID- 1926386 TI - Usefulness of defibrotide treatment during organ procurement and preservation in rats. PMID- 1926387 TI - Extended preservation of dog kidneys with modified UW solution. PMID- 1926388 TI - Usefulness of diltiazem in reducing the incidence of acute tubular necrosis in Euro-Collins-preserved cadaveric renal grafts. PMID- 1926389 TI - Efficacy of UW vs Euro-Collins solution in paired cadaveric kidneys: a prospective study. PMID- 1926390 TI - Incidence, grading, and resolution time of procurement and/or preservation injury in cadaveric vs living donor kidney grafts. PMID- 1926392 TI - Liver preservation in UW and HTK solution: the influence on sinusoidal perfusion after liver transplantation. PMID- 1926391 TI - Ringer's lactate vs serum albumin as a flush solution for UW preserved liver grafts: results of a prospective randomized study. PMID- 1926393 TI - Amino acids to suppress reperfusion injury after liver preservation. PMID- 1926394 TI - Rapid screening of organ preservation solutions based on the determination of the active uptake of alanine by endothelial cells. PMID- 1926395 TI - Effect of diltiazem in the prevention of acute tubular necrosis, acute rejection, and cyclosporine levels. PMID- 1926396 TI - Membrane stabilizing effects of glycine during kidney cold storage and reperfusion. PMID- 1926397 TI - Evaluation of the functional capacity of kidneys transplanted with long periods of cold ischemia time. PMID- 1926398 TI - Preservation of cadaveric kidneys longer than 48 hours: comparison between Euro Collins solution, UW solution, and machine perfusion. PMID- 1926399 TI - Comparison of simple hypothermic storage, pulsatile perfusion with Belzer's gluconate-albumin solution, and pulsatile perfusion with UW solution for renal allograft preservation. PMID- 1926400 TI - Prediction of renal function by intraoperative renal blood flow and renal vascular resistance during kidney transplantation. PMID- 1926401 TI - Evaluation of kidney grafts in the BN rat after variable perfusion flow rates: microscopic aspects and intracellular ATP estimation. PMID- 1926402 TI - Comparison of PBS, HTK, and UW solutions for kidney preservation. PMID- 1926403 TI - Use of UW solution versus Euro-Collins solution in kidney transplantation from cadaveric donors. PMID- 1926404 TI - Pretransplant evaluation of kidney vasculature by image-guided volume selective 19F NMR spectroscopy. PMID- 1926405 TI - Mechanism of hypothermic cell death: glutathione prevents injury in hepatocytes during hypothermic (4 degrees C) preservation. PMID- 1926406 TI - 31P nuclear magnetic resonance study of phospholipid metabolites in cold-stored liver. PMID- 1926408 TI - Perioperative hydration improves preservation of rat kidneys. PMID- 1926407 TI - Extended cold preservation time (20 hours 20 minutes) of a human liver graft by using cardioplegic HTK solution. PMID- 1926409 TI - Cold reflush of stored livers with anoxic solution--A31P NMR study of metabolic changes in rat liver. PMID- 1926410 TI - The role of prostaglandins in reperfusion injury after liver transplantation in pigs. PMID- 1926413 TI - Prostaglandin synthesis and survival after orthotopic liver transplantation in pigs. PMID- 1926411 TI - Changes in hepatic tissue water content in EC-, UW-, and HTK-preserved livers tested in a pig liver transplant model. PMID- 1926412 TI - Role of free radicals and energy synthesis on primary graft nonfunction in liver transplantation. PMID- 1926414 TI - Cold preservation of a human liver in University of Wisconsin solution for 36 hours: a morphological and biochemical study. PMID- 1926415 TI - Cytological analysis of preservation injury in liver transplantation. PMID- 1926416 TI - Role of opioid antagonists in the rat liver ischemia model. PMID- 1926417 TI - Effect of a 21-aminosteroid and/or adenosine in the ischemic rat liver. PMID- 1926418 TI - Anatomic distribution of preservation solutions during canine hepatic procurement. PMID- 1926419 TI - Exchange of pancreata and islets between centers for experimental islet transplantation in the pig. PMID- 1926420 TI - Mechanisms of ATP depletion in the cold-stored heart. PMID- 1926421 TI - Cardiac preservation assessed by rat heterotopic heart transplantation. PMID- 1926422 TI - Limitation of free radical injury by reduced glutathione: an effective means of improving the recovery of heart transplants. PMID- 1926423 TI - Evaluation of rewarming conditions for cold-stored cardiac myocytes. PMID- 1926424 TI - Comparison of continuous perfusion and simple cold storage for rabbit heart preservation. PMID- 1926425 TI - Effects of hypothermic storage and perfusion on rabbit heart ATP and enzyme release. PMID- 1926427 TI - Influence of human donor operation and isolation techniques on the viability of islets of Langerhans. PMID- 1926426 TI - Protective effect of nalmefene and naloxone on the ischemically damaged small bowel. PMID- 1926428 TI - Importance of donor blood chemistry data (AST, serum sodium) in predicting liver transplant outcome. PMID- 1926429 TI - Study of liver preservation: the use of University of Wisconsin or Euro-Collins solutions alone or in a combined method. PMID- 1926430 TI - The possibility of resuscitating livers after warm ischemia injury. PMID- 1926431 TI - Preservation of isolated intestinal segments using the University of Wisconsin solution. PMID- 1926432 TI - Triiodothyronine replacement, the euthyroid sick syndrome, and organ transplantation. PMID- 1926433 TI - Basic principles of donor management for multiorgan removal. AB - Prime quality organs are a scarce resource best fostered by widespread education of critical care physicians in the principles of donor management, and by the provision of expert donor teams (two surgeons, one anesthetist, one nurse) to set consistent high standards of care during organ retrieval. PMID- 1926434 TI - High levels of glycogen in the donor liver improve survival after liver transplantation in rats. PMID- 1926435 TI - Hormonal response to brain death. PMID- 1926436 TI - Organization of a brain death unit in a Paris suburb hospital. PMID- 1926437 TI - Effect of duodenal culture and postoperative infection on the long-term function of pancreaticoduodenal grafts. PMID- 1926438 TI - Reliability of the MEGX test in the selection of liver grafts. PMID- 1926439 TI - Multiple risk factor analysis of delayed graft function (ATN) after cadaveric transplantation: positive effect of lidocaine donor pretreatment. PMID- 1926440 TI - Hormonal therapy and metabolic support efficiency as a criterion in donor heart preoperative evaluation. PMID- 1926441 TI - Inotropic support in 50 brain-dead organ donors: repercussion on renal graft function. PMID- 1926442 TI - Endocrine pancreas after brain death: preliminary results. PMID- 1926443 TI - Influence of donor data on the outcome of liver transplantation. PMID- 1926444 TI - Intraoperative hemodynamic heterogeneity of brain dead organ donors. PMID- 1926445 TI - Arterial blood ketone body ratio as an indicator for viability of donor livers. PMID- 1926447 TI - 99mTc-HMPAO cerebral scintigraphy in the diagnosis of brain death. PMID- 1926446 TI - Organ donor management: review of 68 consecutive cases. PMID- 1926449 TI - Usefulness of dopamine in the maintenance of hemodynamic parameters in brain-dead dogs. PMID- 1926450 TI - Effects of substitutive triiodothyronine therapy on intracellular nucleotide levels in donor organs. PMID- 1926448 TI - Do barbiturates in brain-dead organ donors have a deleterious effect on early renal graft function? PMID- 1926451 TI - Ethical aspects of living donation. PMID- 1926452 TI - Organ donation in blacks: the next frontier. PMID- 1926453 TI - Organ donation--world experience; the Middle East. AB - Many countries in the Middle East began renal transplantation in the late 1970s and the 1980s. In many countries transplantation has evolved through distinct stages of development, and at present living-related donors continue to be the main source of kidneys. Islamic opinion has been strongly in favour of transplantation of organs from both living and cadaveric donors. Brain death as a criterion of death was accepted by Islamic Jurists in 1986, and in Saudi Arabia about 35% of all transplants are from cadaveric donors. Some patients continue to go to neighbouring countries to buy kidneys for transplantation; there is evidence that this practice has resulted in unacceptable morbidity and mortality, and is currently associated with a risk of at least 1:18 of acquiring HIV infection. Extrarenal solid organ transplantation is very new, with heart transplants being performed in Turkey, Jordan, and Saudi Arabia. Liver transplants have been initiated in Turkey and Kuwait. The favourable religious rulings and the resources available should enable transplantation to develop rapidly in the next few years in the Middle East and West Asia. PMID- 1926454 TI - Ethics in organ donation: contrasts in two cultures. AB - 1. For cadaveric organs in the West, there are many avenues that should be pursued in order to increase the supply. Most of the measures under "giving" in Table 2 are ethical, though we do not accept the implication that those who enroll, in advance, as future organ donors should thereby obtain priority for their own possible future transplant organ needs. 2. "Legislated taking" could be ethically justified if shown to be acceptable to most persons in a society or culture, with provision for opting out for those with minority opinions and beliefs. Such evidence should be sought, and acted upon if found to be present. It certainly warrants a strong public education thrust. 3. Possibilities should be explored for nonmonetary rewarding of families of the decreased, in ways that would not foreclose on families giving authorization for purely altruistic reasons. Direct money payments, "buying," will never outweigh the ethical arguments against the practice, in our opinion. There are other societal avenues by which to pursue the perfectly acceptable goals of indirect altruism. 4. For kidney donations from unrelated living donors in India, a case is made for considering rewarded gifting as being ethically acceptable if it is defined in the way that it is carefully defined for this article, provided it meets the criteria for indirect altruism of a panel of social peers, and also is linked to measures of mandated philanthropy (decided also by a panel of social peers), for the reasons given. This is a balance of societal burden (in allowing rewarded gifting) by the ensured benefit to the seller (to prevent his victimization) plus a required benefit to society by seller's philanthropy. The setting of these balances should be decided by a panel of social peers. Such acceptance would not necessarily pass muster for other cultures than the one for which it is designed. 5. All forms of commerce, included that described in the preceding paragraph, become ethically unacceptable if the regulations governing them cannot realistically be enforced. This is a crucial point, a requirement for ethical cogency. PMID- 1926455 TI - Present status of kidney donation in Japan. PMID- 1926456 TI - Altruism, self-determination, and organ procurement efficiency: the European experience. The Leuven Collaborative Group for Transplantation. PMID- 1926457 TI - Organ donation and transplantation in Latin America. PMID- 1926458 TI - Transplant coordinators in Rio Grande do Sul, Brazil: initial analysis. PMID- 1926459 TI - Aspects of the Argentine Transplant Program: a 12-year review (1978-1990). PMID- 1926460 TI - Impact of the opting-out system on kidney procurement in Singapore. PMID- 1926461 TI - Organ donors reported to the Hellenic Transplant Service during the last 5 years. PMID- 1926462 TI - Multiorgan donation program in the Moscow Region of the USSR: present status and future prospects. PMID- 1926464 TI - Medical care of end-stage renal disease in 52 countries: evolution since 1975 and potential activity for the next 5 years. PMID- 1926463 TI - Public opinion regarding organ donation in Chile. PMID- 1926465 TI - Attitudinal barriers to organ donation among black Americans. PMID- 1926466 TI - Comparison of the mortality and morbidity rate between proper and unconventional renal transplantation using organs from executed prisoners. PMID- 1926467 TI - Utilization of altruistic marketing strategy for organ procurement. PMID- 1926468 TI - Standardized education program in organ procurement for transplant coordinators. PMID- 1926469 TI - Renal transplantation in the state of Rio Grande do Sul, Brazil. PMID- 1926470 TI - Catalonia: 25 years of renal transplantation--success of a regional organization. PMID- 1926471 TI - Donor detection and organ procurement in the Basque Autonomous Community: general data. PMID- 1926472 TI - Cadaver kidney harvesting in the region of Rijeka, Yugoslavia. PMID- 1926473 TI - Impediments to successful organ procurement in the "required request" era: an urban center experience. PMID- 1926474 TI - Method of organ procurement: transplant coordination team. PMID- 1926475 TI - Multiorgan procurement in France-Transplant: "Centre-Ile-de-France" Region (SRCIFT). PMID- 1926476 TI - France-Transplant: the French Network for Organ Procurement and Transplantation. PMID- 1926477 TI - Organ procurement costs in southern California. PMID- 1926478 TI - Organ donation from trauma victims. PMID- 1926479 TI - Loss of donor livers and donor hearts: a retrospective study of organ donation in The Netherlands. PMID- 1926480 TI - Increases in organ donation refusals and the efficiency of a transplant program. PMID- 1926481 TI - Which donor factors have an influence on recipient and graft survival? Retrospective analysis of 308 renal transplants at a single centre. PMID- 1926482 TI - Liver transplantation in Turkey. PMID- 1926483 TI - Multiorgan harvesting from heart-beating donors in Turkey. PMID- 1926484 TI - Living unrelated or second-degree related kidney transplantation. PMID- 1926485 TI - Renal transplantation from distant relatives. PMID- 1926486 TI - Living related donor kidney transplantation in 349 consecutive recipients. PMID- 1926487 TI - Renal transplantation costs: an economic analysis and comparison with dialysis costs. PMID- 1926488 TI - Procurement of kidney grafts from non-heart-beating donors. PMID- 1926489 TI - Non--heart-beating donors: an alternative organ source in kidney transplantation. PMID- 1926490 TI - Successful renal transplantation with kidneys from asystolic donors maintained under extracorporeal cardiopulmonary bypass: 6-month follow-up. PMID- 1926491 TI - Long-term renal function of kidneys transplanted from non-heart-beating cadaver donors. PMID- 1926492 TI - Kidney harvesting from non-heart-beating donors (NHBD): a surgical approach. PMID- 1926493 TI - An initial wash-out solution for "in situ machine wash-out". PMID- 1926495 TI - Heart transplantation (HTx) with donors over 40 years of age. PMID- 1926494 TI - The elderly donor. PMID- 1926496 TI - Impact of donor age on graft function in 1180 consecutive kidney recipients. PMID- 1926498 TI - Transplantation of small pediatric cadaver kidneys into adult recipients. PMID- 1926497 TI - Age greater than 50 years is not a contraindication for liver donation. PMID- 1926499 TI - High organ retrieval rate: a disincentive to organ sharing? PMID- 1926500 TI - Recipient race does not influence waiting time for a cadaveric renal transplant- one organ procurement organization's experience. AB - There was no statistical significance to the differences in waiting time for cadaveric renal transplant by race. Whether for first transplant or second or greater, any differences in waiting time could not be accounted for by the recipient's race. CAUC made up 58% of the waiting list, 65% of the recipients, and 87% of the donors. The corresponding numbers for AA are: 38%, 29%, and 10%, respectively. More regional serum-sharing trays may be needed in order to expose recipients with high PRA to as many donors as possible in order to lessen their waiting time. It should be noted that fewer HLA mismatches occurred when donor and recipient race were identical. In light of this data, more study is needed to determine the relationship between donor and recipient race, corresponding HLA mismatches, and graft survival. If antigen-matching is found to increase graft survival, then an increase in minority donations will be required. Until that time, under the current allocation system and with the predominance of Caucasian donors, it is likely that Afro-Americans will continue to receive kidneys that have more HLA antigen mismatches than if Afro-Americans donated in numbers equivalent to their percentage of the waiting list. PMID- 1926501 TI - Transplantation of shipped full-house, HLA-identical kidneys versus local, poorly matched grafts--does a shorter cold ischemia time outweigh a poorer HLA match? PMID- 1926502 TI - Outcome of organs shared in the "domino" procedure. PMID- 1926503 TI - Hormonal alteration and pituitary function during course of brain-stem death in potential organ donors. PMID- 1926504 TI - The use in pediatric transplantation of livers from donors who died from anoxia. PMID- 1926505 TI - Nonoliguric reversible acute renal failure in an obese living donor. PMID- 1926506 TI - Metabolic disorders in cadaveric kidney donors and initial nonfunction of the kidney graft. PMID- 1926507 TI - Impact of donor age in kidney transplantation. PMID- 1926509 TI - Kidney transplantation from aged donors. PMID- 1926508 TI - Influence of donor and recipient age on graft survival rate after renal transplantation with a protocol of low CyA doses. PMID- 1926510 TI - Medical risk and benefit in elderly living renal donors--our experience. PMID- 1926511 TI - Modified extravesical ureteroneocystostomy and routine ureteral stenting in cadaveric renal transplantation. PMID- 1926512 TI - Donor transmitted disease: cancer. PMID- 1926513 TI - Hepatitis C virus in renal transplantation. PMID- 1926514 TI - IgA nephropathy as a donor-transmitted disease in renal transplant recipients. PMID- 1926515 TI - Transmission of cancer with cadaveric donor kidneys. PMID- 1926516 TI - Significance of bacterial contamination of cadaver donor renal allografts before transplantation. PMID- 1926517 TI - Donor-related non-Hodgkin's lymphoma in a renal allograft recipient. PMID- 1926518 TI - Accidental transplantation of a kidney with stones: case report. PMID- 1926519 TI - Chagas disease and kidney transplantation. PMID- 1926520 TI - Influence of positive cultures in donor and preservation medium on development of infection in cadaveric kidney transplant recipients: beneficial effects of antibiotic coverage at the time of nephrectomy. PMID- 1926521 TI - Organ transplantation with undetected donor neoplasm. PMID- 1926522 TI - Hepatitis C virus antibodies in hemodialysed and in renal transplant patients: correlation with chronic liver disease. PMID- 1926523 TI - Possible transmission of malaria by liver transplantation. PMID- 1926524 TI - Tissue banking. PMID- 1926525 TI - Nonrenal organ sharing in Spain: the first 3-year (1987 to 1990) experience. PMID- 1926526 TI - Results with shared, six-HLA-antigen-matched cadaver renal transplants. PMID- 1926527 TI - The clinical relevance of HLA matching in heart transplantation: impact on rejection and donor-directed cytotoxicity of graft infiltrating lymphocytes. PMID- 1926528 TI - Single center experience with renal allograft sharing. PMID- 1926529 TI - More favorable clinical course in kidney allograft recipients due to HLA-B+ DR matching. PMID- 1926530 TI - Technique and results of organ sharing for heart and isolated single or double lung transplantation. PMID- 1926531 TI - The experience of the "Sao Paulo Interior Transplante" with a multifactorial system for selection of cadaver kidney recipients. PMID- 1926532 TI - Immunogenetic characteristics of donors of allogeneic organs in Leningrad. PMID- 1926533 TI - Improvement in HLA matching and graft survival achieved by organ sharing. PMID- 1926534 TI - Kidney transplant policy on HLA matching and waiting list. PMID- 1926535 TI - Flow cytometry crossmatching in donor/recipient selection. PMID- 1926536 TI - Prenephrectomy tissue typing using donor lymph node cells: a reliable and safe way of shortening cadaver kidney ischemia time. PMID- 1926537 TI - The impact of the presumed consent law and a decentralized organ procurement system on organ donation: quadruplication in the number of organ donors. PMID- 1926538 TI - Does quality of donor crossmatch material influence organ allocation? A survey of the transplant units in the United Kingdom and Ireland. PMID- 1926540 TI - A technique for multiorgan harvesting in rats--an educational tool in transplantation. PMID- 1926539 TI - European urgent liver graft scheme: a prospective study. PMID- 1926541 TI - "Go on--say yes": a publicity campaign to increase commitment to organ donation on the driver's license in New South Wales. PMID- 1926542 TI - The role of public education in cadaveric transplantation in Saudi Arabia. PMID- 1926543 TI - Global organ sharing: dreams and realities. PMID- 1926544 TI - Principles of world cooperation in transplantation. PMID- 1926545 TI - Progress in organ procurement: the non heart-beating cadaver donor and other issues in transplantation. PMID- 1926546 TI - Hyperreactive malarial splenomegaly in pregnancy. AB - Hyperreactive malarial splenomegaly (HMS) is common in many tropical areas and particularly affects women of reproductive age. It is associated with anaemia which can be debilitating in patients already compromised by anaemia due to poor nutrition and pregnancy. The course of the disorder in pregnancy is commonly punctuated by episodes of haemolytic anaemia which can be life-threatening to the mother and cause increased fetal morbidity and loss. Management of the chronic state consists of lifelong anti-malarial therapy supplemented by haematinics. Blood transfusions may be required to treat episodes of severe haemolysis. PMID- 1926547 TI - Effects of skin contactants on evolution of atopic dermatitis in children: a case control study. AB - There is little published literature on the effects of skin contactants during early infancy on eventual development of atopic dermatitis (AD). The purpose of this study was to determine whether or not a relationship exists between the use of skin care products in early infancy and the subsequent development of AD. We studied a group of 54 Kenyan children with AD and 63 age and sex matched controls. Emollients had been used to lubricate the skin during early infancy in a similar proportion of children in both groups (odds ratio = 0.33; 95% CI = 0.14, 0.80). Similarly, no association was found between the use of toilet soaps or laundry detergents in early infancy and development of AD. These findings suggest that baby soaps and vaseline petroleum jelly can safely be used in the skin care of AD susceptible individuals. PMID- 1926549 TI - Ectopic pregnancies and intraoperative autotransfusion. AB - Ruptured ectopic pregnancies are common in the tropics. They rapidly lead to anaemia and shock, but autotransfusion is simple and safe and can be practised easily by the simplest of surgical departments. PMID- 1926550 TI - Utilization of trained unemployed youth in community cancer screening using seven warning signs. PMID- 1926548 TI - Aetiology and management of dyspepsia in Africa. PMID- 1926551 TI - Evaluation of HIV testing of blood spotted paper samples. PMID- 1926552 TI - Supportive treatment of adult lobar pneumonia. PMID- 1926553 TI - Antimicrobial susceptibility of bacterial pathogens isolated from CSF in Barbados. PMID- 1926554 TI - Diagnosis of low respiratory infection. PMID- 1926555 TI - Tinnitus, quackery and folklore. PMID- 1926556 TI - Coathanger wire, as an aid to endotracheal intubation. PMID- 1926557 TI - Spontaneous rupture of the spleen. PMID- 1926558 TI - Tuberculosis in malnourished children. PMID- 1926559 TI - Amputation of the right big toe in child bicycle passengers. PMID- 1926560 TI - Trends in disease admissions and deaths in church hospitals in Tanzania, 1971 1985. PMID- 1926561 TI - The value of mapping apocrine-bearing skin before surgical excision in hidradenitis suppurativa: experience in Kaduna. PMID- 1926562 TI - 'Traditional' alcohol in surgical antisepsis in a rural African setting: a kind of intermediate technology? PMID- 1926563 TI - Ileo-colic intussusception complicating heavy Trichuris trichiura infection. PMID- 1926564 TI - A practical approach to the clinical problems of the HIV-infected adult in the tropics. PMID- 1926565 TI - Strengthening district health systems in Ghana: the experience of Ejisu District. PMID- 1926566 TI - [The detection of high-risk groups among workers in contact with heavy metals based on an analysis of chromosome aberrations and sister chromatid exchanges]. AB - Heavy metal salts, the workers from molybdenum, tungsten and cobalt plants to make in contact with, reveal their mutagenic activity. Individual sensitivity to heavy metal salts has been analyzed through the example of molybdenum. Chromosome aberrations and sister chromatid exchanges have been studied for the regularities of their formation in lymphocytes of workers depending on the length of service. Sensitivity of tests of chromosome aberrations and sister chromatid exchanges has been compared to reveal genetic consequences of these types of the effects. PMID- 1926567 TI - [The detection of mutations arising in human populations]. AB - The problem on screening of de novo mutations, arising in populations, by the method of search for rare protein variants has been critically discussed. The data on monomorphic loci and rare variants of human blood proteins, and platelet monoamine oxidase previously not studied in terms of populations are presented. A method is suggested to screen mutations, using restriction analysis of mitochondrial DNA in mouse populations. PMID- 1926568 TI - [The restoration by Escherichia coli RecA protein of the survival of gamma irradiated HeLa cells reduced by the DNA repair inhibitors caffeine and 3 aminobenzamide]. AB - It is confirmed that inhibitors of DNA repair caffeine and 3-aminobenzamide decrease the survival of gamma-irradiated HeLa cells. It is shown that the decreased survival of irradiated cells is reversed when Escherichia coli RecA protein is introduced into cell nucleases with the aid of liposomes. This effect is more expressed in caffeine-treated (before or after irradiation) than in 3 aminobenzamide-treated (before irradiation) cells. It is suggested that E. coli 38 kD RecA protein may compensate the function of HeLa RecA-like protein, inhibited by DNA repair inhibitors, which is necessary for the repair of single strand breaks and double-strand breaks of DNA. PMID- 1926569 TI - [The effect of UV microirradiation of the centrosome on cell behavior. I. The destruction of the mitotic spindle and disruption of cell division during irradiation in the metaphase]. AB - A 5 second UV microirradiation of the centrosome during the early metaphase leads to a rapid (within 5 minutes) chromosome shift towards the normal pole and disorganizes the spindle. The later metaphase plate is also disorganized, chromosomes being situated chaotically in the central part of the cell. Numerous (up to 10 or more) microtubule convergence centers are observed instead of the spindle. 2-4 hours after the microirradiation some cells may enter cytotomy. The microirradiation of chromosomes and cytoplasm in similar and greater doses (exposure up to 15 seconds) did not lead to disorganization of the spindle and did not effect the normal completion of mitosis. Sometimes the 5 second microirradiation in the middle metaphase also blocked anaphase, but the microirradiation within the last 5 minutes of the metaphase always failed to block anaphase and normal completion of division. PMID- 1926570 TI - [The stimulating effect of prolactin on the neurite growth of sensory neurons in an organotypic culture]. AB - Prolactine was found to promote neurite extension in chick embryo dorsal root ganglia in vitro. This hormone was active at the concentration 10-50 ng/ml provided extensive neurite outgrowth in the bioassay, compared to the control. The liquor from patients with prolactinoma was also found to promote neurite extension. This fact may be used for prolactinoma diagnostics. PMID- 1926571 TI - [DNA synthesis in heterokaryons obtained by the fusion of polymorphonuclear leukocytes and cultured cells possessing different proliferative potentials]. AB - Heterokaryons between terminally differentiated polymorphonuclear leukocytes (PL) and culture cells of different proliferative potentials: mouse and rat embryo fibroblasts (EFM, EFR); immortal cells NIH 3T3 and E2; malignant cells NCC2, L929, He239 and SV 3T3,--were obtained by means of electrofusion. Radioautographic study of 3H-thymidine incorporation in the nuclei of heterokaryons showed that all the cells taken for fusion were able to induce reactivation of DNA synthesis in PL nuclei, however, with different rates: 7-37% for EFM and NIH 3T3 and 20-40% for malignant cells. The presence of oncogenes Elan in E2 cells and ras in NCC2 cells increased the rate of PL reactivation approximately twice as compared with the cells of original lines (EFR and NIH 3T3, correspondingly). In parallel to reactivation of DNA synthesis in PL nuclei inhibition of the synthesis in culture cell nuclei in the same heterokaryons was found. The rate of inhibition was about 70% for non-malignant and 23, 40 and 18% for NCC2, L and SV 3T3 cells, respectively. He239 cells, transformed by a temperature-dependent mutant of virus SV40 showed at permissive temperature the increased capacity of inducing reactivation of PL nuclei, though He239 cells susceptibility to inhibitory action of PL nuclei did not change with temperature. According to the behaviour in heterokaryons PL were found to be similar to chick erythrocytes, but differing from them by a pronounced inhibiting effect upon DNA synthesis in the nuclei of malignant cells. PMID- 1926572 TI - [The competition of 2 types of epithelial layers in mixed cultures]. AB - The interaction of epithelial cells was studied in mixed cultures by phase contrast, time-lapse microcinematography, transmission and scanning electron microscopy. Epithelial cells, united into monolayer sheets with smooth apical surfaces, can be competing for substrate lamellae at the lower surfaces and force out each other from the substrate up to full elimination. The competition of cells for territory may be an important factor in morphogenesis in vivo. PMID- 1926573 TI - [The in vivo arrest of Ehrlich ascitic carcinoma cells in the G2 phase of the cell cycle]. AB - Evidence for arrested G2 cell subpopulation in the Ehrlich ascite carcinoma has been provided using flow cytometry stathmokinetic and bromdesoxyuridine--Hoechst 33258 techniques. After exposure in DME--F-12 media G2-arrested cells synchronically enter mitosis and then move trough G1 period. Durations have been measured for G1. G2 phases and G2-G1 transition. PMID- 1926574 TI - [Lysosomal enzymes and natural killer activity]. AB - The natural killer activity (NKA) of human mononuclear cells and the activity of the lysosomal enzymes of these cells (arylsulfatase, acid phosphatase and beta glucuronidase) has been studied in norm and under human lung cancer. The mononuclear cells were isolated from peripheral blood of 10 healthy donors and 20 patients with lung cancer of II-III stages. Under the action of mononuclear cells on the target cells (human erythroleukosis cells K-562 labeled with 3H-uridine) the NKA of mononuclear cells of patients was seen to decrease (cytotoxic index = 54.8 +/- 6.4%), in comparison with that of healthy donors (cytotoxic index = 65.1 +/- 4.5%). Simultaneously a decrease in arylsulfatase activity (0.05 +/- 0.01 nmoles/10(6) cells/min) was found in comparison with the control value (0.11 +/- 0.01 nmoles/10(6) cells/min). In 2-3 weeks after the operation the NKA value (cytotoxic index = 50.2 +/- 5.8%) was restored and arylsulfatase activity (0.09 +/- 0.02 nmoles/10(6) cells/min) was increased. There was no correlation between the NKA value and the activities of acid phosphatase and beta-glucuronidase. The parallelism observed between changes in NKA value and arylsulfatase activity may suggest a possible participation of this enzyme in the killing mechanism at the stage of cerebroside sulfate ester degradation of the target cell membrane to initiate the lytic events. PMID- 1926575 TI - [A comparative evaluation of the glycogen content in the peripheral blood of normal cattle and in chronic lymphoid leukemia]. AB - Peripheral blood lymphocytes in cows of four groups (healthy, exposed to leucosis, those affected by leucosis at early or at developed stages) were tested for their glycogen contents by the two following methods: the semiquantitative PAS technique (Shabadash, 1947) and the quantitative cytofluorimetric variant of PAS reaction in the M. V. Kudriavtseva modification (1970). The results show no difference between the 1st and 2nd groups as concerns the number of leucocytes and the relation of the number of glycogen-positive cells to the share of lymphocytes in the peripheral blood. In the 3rd and 4th groups, the increase in glycogen in individual cells paralleled with the increase in the number of PAS positive lymphocytes, according to the Shabadash method. On comparing the results of the study of glycogen contents in lymphocytes of healthy and leucosis suffering cows, the two methods used proved to coincide very well. Hence, both the methods may be used for the aims of diagnosis of hemoblastosis in farm animals. PMID- 1926576 TI - [An evaluation of the conformational changes in the superhelical DNA of eukaryotic cells by direct nucleoid fluorometry. II. The characteristics of the change in acridine orange fluorescence in studying the superhelical DNA of rat thymocytes]. AB - Comparative studies of acridine orange (AO) and ethidium bromide interactions with supercoiled DNA (scDNA) of thymocytes were performed in which various conformational changes were induced. AO may be efficiently used for evaluation of conformational alterations of scDNA. Moreover, employing the maximum values of AO fluorescence allows to determine the maximum levels of scDNA relaxation. PMID- 1926577 TI - [The microelectrophoresis of the DNA in individual intact and gamma-irradiated thymocytes]. AB - The in vitro gamma-irradiated mouse thymocytes were embedded in low melting agarose at 37 degrees C. After getting at 4 degrees C, the cells were lysed in neutral detergent solution containing proteinase K and ethidium bromide. Microscopic visualization of single lysed and stained cells showed the presence of the central "core" (nuclear matrix) surrounded with "halo" (relaxed nuclear DNA). During electrophoresis (2-5 V/sm, 5 min) this "halo" migrated towards the anode forming a "tail". The use of microdensitometric system provided measuring the size of the tail (L) and quantity of migrated DNA (S) for individual cells as well as obtaining the distribution of these parameters among the cells. The latter may be characteristic of heterogeneity of the cell population. It was shown that L and S increased linearly with the dose irradiation at least between 0.2 and and 5.0 Gy. In irradiated thymocyte (3 Gy) the DNA repair occurred within 10-20 min, but residual DNA damage could be observed even after 60 min of incubation. These damages may initiate the degradation of DNA in irradiated thymocytes that was observed after the repair of DNA. PMID- 1926578 TI - [Interaction of lipoproteins in blood serum with steroid hormones]. AB - Interaction of human and serum lipoproteins with steroid hormones (corticosterone and cortisol) was studied. Methods of fluorescence quenching titration and equilibrium dialysis were used for quantitative evaluation of VLDL, LDL and HDL glucocorticoid-binding ability. Association constants were found to be 0.6-2.0 x 10(6) M-1 for corticosterone and 4.0-8.0 x 10(6) M-1 for cortisol. The number of binding sites varied from 3 to 300 for different classes of lipoproteins. PMID- 1926579 TI - [Membranotropic action of cardiotonic agents and ubiquinone]. AB - Interaction of cardiotonic drugs (strophantidine acetate, suphan, para-oxybenzoic acid) and ubiquinone with phospholipid bilayers has been studied. Exothermic effect of the reaction followed by an increase in microviscosity and hydrophobicity of the bilayer from cardiolipin, but by a decrease of the microviscosity of the bilayer from lecithin has been estimated. A correlation is observed between changes in the lecithin bilayer fluidity and the heat effect of the interaction at the initial period of time after mixing of reagents. PMID- 1926580 TI - [Accumulation of thiamine and its metabolites in rat liver cells and mitochondria]. AB - Penetration of thiamine and its metabolites through the liver mitochondria and blood cells of white rats has been studied. It is shown that the catabolic forms of thiamine, thiochrome and 4-methyl-5 oxyethylthiasole penetrate through the mitochondria membranes at a larger extent than thiamine and its phosphoric esters. An increase in concentration of thiamine and its metabolites in the incubation medium from 0.1 mM to 3.2 mM leads to intensification of this process. The larger permeability of thiochrome and 4-methyl-5 oxyethylthiasole through biological membranes permits explaining the principles of catabolic thiamine forms removal from the tissues and organism. PMID- 1926581 TI - [Glycation of proteins and methods of its assessment]. AB - Glycation of purified preparations of amino acids, hemoglobin and albumin has been studied. The content of glycated blood proteins in children with different diseases (diabetes mellitus, thyroid gland function disturbances, obesity, neurodermititis) has been determined. Application of the protein glycation for diagnosis and prediction of diseases is proved to be expedient. PMID- 1926582 TI - [Plasminogen activation by a tissue activator and effector properties of fibrinogen-N-terminal disulfide (N-DSK) fibrin complex]. AB - Fibrinogen-NDSK complex is a model of protofibril having some features of the fibrin polymer structure. This complex has been studied for its ability to stimulate the plasminogen activation by t-PA. The fibrinogen-NDSK complex have increased the rate of plasminogen activation by t-PA as compared to fibrinogen or NDSK taken separately. This acceleration had slow and fast phases. Lys plasminogen was activated more effectively as compared to glu-plasminogen. The kinetic parameters of glu- and lys-plasminogen activation at fast phase were: Km- 0.18 and 0.015 mu/M, Kkat--0.27 and 0.06 s-1, respectively. Fibrinogen X2- fragments, deprived of alpha C-domains and NH2-end peptides of bB-chains, formed complexes with NDSK, which however did not stimulate the plasminogen activation by t-PA. These findings have shown that the fibrinogen-NDSK complex is an effective stimulator of the plasminogen activation by t-PA. The activating ability of the complex may be due to structures formed in the course of fibrinogen and NDSK polymerization as a result of alpha C-domain interaction. PMID- 1926584 TI - [Effect of ethanol on lipoprotein metabolism in human and animal blood]. AB - The amount and composition of human and animal blood plasma lipoproteins have been studied as affected by low temperature and high doses of ethanol. Results are presented. A conclusion about antiatherogenic properties of low doses of ethanol based on the data of its effect on the system of blood lipoproteins cannot be considered completely proved. Reliable interpretation of the results of the ethanol effect on lipoproteins and atherogenesis processes needs the further study of mechanisms of the ethanol effect on the exchange and modification of the basic classes of lipoproteins and their subfractions, many their peculiarities being not studied yet. PMID- 1926583 TI - [The effect of pH and reversible inhibitors on decarbamylation of acetylcholinesterase]. AB - Decarbamylation rate of membrane-bound methyl- and dimethyl-carbamylated acetylcholinesterase of human erythrocytes and bovine brain is reliably 1.1-1.6 times lower than that of the soluble enzyme. Such reversible inhibitors as tacrine (of non-competition action), ambenonium (mixed action) and galanthamine (competitive type of action) decelerate the decarbamylation rate of acetylcholinesterase. At pH 6 tacrine inhibits the reduction rate of soluble acetylcholinesterase activity of human erythrocytes more intensively than that of membrane-bound acetylcholinesterase. No differences in decarbamylation rate were found for the both forms of the enzyme at pH 8. Tacrine, a non-competitive inhibitor in concentrations below the inhibition constant (Ki = 1.4 x 10(-7) M) exerts the most intensive effect on the decarbamylation rate of methyl- and dimethylcarbamylated acetylcholinesterase of the mouse brain, while ambenonium and galanthamine in concentrations much (tens times) exceeding their Ki (3.1 x 10(-10) M and 4.4 x 10(-7) M, respectively) provide a decrease of the decarbamylation rate. PMID- 1926585 TI - [Glutamate decarboxylase and GABA transaminase activity in the mitochondrial fraction of the dog brain limbic system during postnatal development]. AB - Overall glutamate decarboxylase (GDCase) activity in the initial mitochondrial fraction of the limbic structure is found to be regionally different it increases from the moment of birth up to 1 year, the midbrain reticular formation (RF), where the enzyme activity in the mitochondrial decreases in pups aged 3 month and reincreases in 1 year old dogs being the exception. Overall GABA-transaminase (GABA-T-ase) activity reaches the "adult" level and is the highest: in the hypothalamic and hippocampal mitochondria on the 1st postnatal day; in the limbic cortex (l1 and l2 fields), amygdala and midbrain RF--on the 12-16th postnatal days. During the period from 12-16 postnatal days up to the age of 1 year GABA-T ase activity in the dog limbic system decreases reliably. PMID- 1926586 TI - [Ecdysterone induces the activity of multiple forms of acid phosphatase and malate dehydrogenase in fat bodies of Anterahea pernyi pupae]. AB - The method of electrophoresis in PAAG has been used to study activity of multiple forms of acid phosphatase and malate dehydrogenase of the fat body of Anterahea pernyi pupae in norm and affected by ecdysterone. It is shown that an increase of total activity of acid phosphatase and malate dehydrogenase with administration of a steroid hormone is promoted by growth of activity of certain inducible multiple forms of the studied enzymes. Ecdysterone injection considerably elevates activity of the most electrophoretically mobile form of acid phosphatase and provokes new formation of malate dehydrogenase form. Ecdysterone-induced increase of activity of the studied enzyme forms in the fat body of Anterahea pernyi pupae is blocked by actinomycin D, an inhibitor of transcriptional processes, and by puromycin, a translation inhibitor. These data permit concluding that an increase in activity of the mentioned forms of enzymes observed with hormonal induction is a result of their synthesis de novo and is mediated by the DNA-dependent RNA-synthesis. PMID- 1926588 TI - [Effect of benzodiazepines on NAD binding to synaptic membrane in the rat brain]. AB - The receptor protein solubilized from synaptic membranes specifically binds [14C] NAD (dissociation constant--0.75 microM, capacity of binding sites--0.0125 nmol of metaid per 1 mg of protein). All the studied benzodiazepines (phenazepam, nitrazepam, clonazepam, flunitrazepam) are able to displace [14C] NAD from its receptor sites, the mixed type of inhibition being manifested. An inhibition constant for flunitrazepam, a ligand of benzodiazepine receptors, equals 10 microM. GABA promotes an inhibiting effect of benzodiazepines. It is supposed that neurotropic action of NAD is realized through the GABA-benzodiazepine complex of neuronal membranes. PMID- 1926587 TI - [Properties of the membrane fractions of kidney microsomes from rats with hereditary hypertension induced by stress]. AB - Phospholipid composition of microsomal fraction from a medullar layer of kidneys has been studied in rats of the Wistar and SSHR lines (the latter is a line of animals whose arterial tension rises after a stress). The phospholipid protein ratio for this fraction in the both lines is 0.4. Under the stress the mentioned parameter rises only in the SSHR rats. Phosphatidylcholine amounting to approximately 50% is a basic phospholipid in the microsomal fraction of rats of the both lines. Interlinear differences are associated with the amount of phosphatidyl serine and phosphatidyl ethanolamine: the level of these phospholipids in the Wistar rats is 14 and 8%, that in the SSHR ones--0 and 37%, respectively. After stressing rats of the both lines the phosphatidylcholine amount in the membrane falls to 30%. In this case the level of phosphoinositides and phosphatidyl serine grows in the Wistar rats, the level of phosphatidyl ethanolamine--in the SSHR rats. Microviscosity of microsomal membranes in the range of temperatures 12-38 degrees C is determined using pyrene, a fluorescent probe. Annular lipids in membranes of cells in Wistar rats are characterized by higher viscosity than those in SSHR rats. Stresses promote a decrease of microviscosity in annular lipids of Wistar rats. In hypertensive rats the response of membranes to stress is different in animals of different generations of breeding but introduction of androsole acetate to stressed rats makes microviscosity characteristics of the membranes similar to those of the Wistar rat membranes. PMID- 1926589 TI - [Production of lectin from jack fruit (Artocarpus integrifolia) seeds and its interaction with carbohydrates and glycoproteins]. AB - A method is developed to obtain lectin from jack fruit (Artocarpus integrifolia) seeds using an affinity chromatography on a sorbent prepared from the egg white. The minimum agglutination concentration of human erythrocytes is 80 ng/ml, the molecular weight of the preparation is about 39 kDa, it contains 1.8% of neutral hexoses and 3.1% of hexosamines. PAAG electrophoresis in the alkali system has revealed several molecular forms of lectin isolated by preparative electrophoresis, their properties are investigated. SDS-PAAG electrophoresis has revealed several types of polypeptide chains among which two chains (12 and 14 kDa) are predominant. Lectin possesses affinity to galactosides (not to free galactose) and N-acetylgalactosamine and interacts with O-glycans with high affinity. The preparation has mitogenic activity in optimal concentration 50 micrograms/ml. PMID- 1926590 TI - [Lipid and fatty acid composition of Eisenia foetida]. AB - It is found out that the content of lipids in the biomass of the studied populations of Eisenia foetida is rather high: 2.5-5.2% of the wet mass. The content of phospholipids is 40-55%, C27-sterols--1.5-3.4% of the mass of coarse extracts of lipids. Lipids of tissues contain also 47-54% of saturated (C10-C24) fatty acids as well as to 23% of monoene and to 13% of polyene unsaturated (C14 C22) fatty acids. The acids with the odd number of carbon atoms compose about 25% and acids with a branched carbon chain about 23% of the above percentage. Considerable content of lipids and biologically active fatty acids in tissues of the studied object permits considering it as a promising source of raw materials for production of valuable pharmacological preparations. PMID- 1926591 TI - [Glycosaminoglycans in tissue forming joint elements]. AB - A method is suggested to isolate and purify glycosaminoglycans forming elements of a joint from different kinds of connective tissue. The suggested method has been used to study the amount and composition of glucosaminoglycans in the knee joint tissues of people who had died from different accidents. The cartilage of patella and medial condyle of the femur, synovial membrane, medial meniscus and medial tendon of musculus quadriceps femoris are studied. Differences in the amount and composition of glucosaminoglycans in adults are shown. PMID- 1926592 TI - [Regulation of fructose 1,6-diphosphate transformation in tissues]. PMID- 1926593 TI - [Vitamin E, ubiquinone and ubiquinone-dependent enzymes in experimental myocarditis]. AB - It is shown that a day after introduction of adrenaline which evokes experimental focal myocarditis the level of ubiquinone and vitamin E content in the myocardial mitochondria increases by 56.8 and 122%, respectively. Succinate-ubiquinone reductase activity in mitochondria remains practically unchanged, while NADH ubiquinone-reductase activity considerably falls. 5 days after the focal myocarditis reproduction the content of ubiquinone and NADH-ubiquinone-reductase activity of mitochondria return to the norm, while the vitamin E amount remains higher than in intact animals. 24h after adrenaline introduction the level of succinate-ubiquinone-reductase activity of blood leucocytes considerably grows. It is not normalized even on the 5th day after adrenaline administration. It is supposed that the level of this activity may be an index showing development of the focal myocarditis. PMID- 1926595 TI - [Malaria status]. PMID- 1926594 TI - [Phosphatase activity and level of cyclic nucleotides upon implantation of polyurethane with lactose in the main chain]. AB - Activity of hydrolases, acid and alkaline phosphatases (AP and A1P) in connective tissue capsules as well as the amount of cyclic nucleotides in the rat blood plasma with implantation of polyurethane on the basis of polyoxytetramethylenglycol and 4,4'-diphenylmethane diisocyanate with lactose in the main chain were studied. Data obtained indicate that polyurethane with lactose in the main chain is biocompatible and nontoxic and may be recommended for the purposes of endoprosthesis. PMID- 1926596 TI - [Pregnancy after kidney transplantation]. AB - Renal transplantation is invariably accompanied by improvement in reproductive function. The possibility of conception in women of childbearing age emphasises the need for sensible counselling. Most authorities advise a delay of about two years post-transplantation. This appears to be good advice, because by then the patient will have recovered from the major surgical sequelae, renal function will have become stabilized with a very high probability of allograft survival at five years and immunosuppression will also be at a maintenance level. Renal function should be stable with a S-creatinine less than 130 micromoles/l. About 40% of all conceptions do not proceed beyond the first trimester. The overall complication rate in pregnancy continuing beyond the first trimester is 46%. If complications, usually uncontrolled hypertension, renal deterioration or rejection, occur before 28 weeks of gestation then successful obstetric outcome occurs in 73% compared to 92% when pregnancy is trouble-free before 28 weeks. Remote problems occur in 11% of women after delivery but where the pregnancy is complicated prior to 28 weeks remote problems occur in 24%. It is of course, difficult to know whether problems are precipitated by pregnancy or are time-dependent and would have occurred in any case. PMID- 1926597 TI - [Chronic inflammatory demyelinating polyradiculoneuropathy]. AB - During recent years chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) has been characterized on the basis of clinical and laboratory findings. Immune modifying treatment with glucocorticoids, plasma exchange and infusion of immune globulins has had a therapeutic effect in controlled studies. Decisive for increased therapeutic efforts against CIDP in Denmark is intensified electrophysiological search in patients with polyneuropathy with examination of several nerve segments for evidence of demyelination including conduction block, potential dispersion and reduction of conduction velocity by more than 40%. PMID- 1926598 TI - [A physician-staffed heart ambulance in a rural district. A 1-year trial]. AB - A trial period of one year in which the ambulance service for patients with acute cardiac disease was improved is described. This trial took pace in the County of Vestsjaelland in a mixed urban and rural district with five general practices and with more than fifteen kilometres (9.4 miles) to the county hospital. Two ambulance stations were equipped with defibrillators and the staff were trained in their use. The recommendations made by a subcommittee appointed by the Danish Board of Health were thus fulfilled, but, in addition, the general practitioners/doctors-on-duty were connected with the arrangement. They were equipped with radios by which they could communicate with the ambulance stations. If the leader of the ambulance station considered, on the basis of the alarm, that a patient with acute cardiac disease was involved, the doctor-on-duty in the district concerned was contact so that he could come and participate in the treatment unless prevented by other work. An attempt was made to assess the effect of an arrangement such as this on survival of patients, the extent to which medical assistance can be obtained and the extent of the actual medical assistance. During the trial period, 158 turn-outs occurred to the approximately 30,000 population in the district concerned. The total number of emergency ambulance turn-outs was 1,200, 41 of these were patients with clinical cardiac arrest and 56 to patients with other forms of acute cardiac disease. Sixty-one patients were found to have conditions other than cardiac diseases. It proved possible to provide medical assistance in 79% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1926599 TI - [Does alternative medical equipment result in pacemaker dysfunction?]. AB - Employment of alternative therapeutic measures is increasing in Denmark. Some of this equipment employs magnetic fields in the therapeutic strategy. This may involve interference with the function of electronic equipment. Electronic interference may, in certain situations, influence pace-maker function. In the worst cases, it may be imagined that the situation may endanger life for persons who are dependent on pace-makers. When a pace-maker is exposed to a magnetic field of a certain strength, the type of pacing is changed to a fixed frequency. Some pace-maker types carry out a built-in test programme when exposed to magnetic influence (vario- or threshold test). The magnetic influence may involve discomfort for the wearer of the pace-maker, but does not endanger life. Investigation of stationary magnetic fields from alternative medical equipment resulted in disturbance of pace-maker function in an isolated case. Pulsating magnetic fields may result in possible induction of electric current which may be wrongly interpreted by the pacemaker. The results of this may be that the pace maker does not send out pace impulses. As protection from continuous electric noise, pace-makers have a built-in electronic safety circuit (dual-demand). When this is activated, the pace-maker will stimulate with a basic frequency. It is recommended that equipment which employs magnetic fields in treatment should be measured before being employed on pace-maker wearers. PMID- 1926601 TI - [Residual metastases from testicular cancer. CT as a diagnostic and strategic adjuvant]. AB - Forty-nine young males with advanced testicular cancer treated between March 1982 and June 1989 comprised a 49/588 (8%) subgroup with distant metastases to the retroperitoneum, mediastinum and lungs, and required mandatory surgery on basis of the risk for reactivation of "slumbering" malignant components in tumor tissue temporarily inactivated by chemotherapy and/or radiotherapy. Preoperative CAT scan was carried out with the intention of mapping regional pathology related to the size, number, burden of the tumor tissue, and the occasional and prognostic ominous invasion of the great vessels. Regarding radical surgery, the positive predictive value of CAT-scan was found to be 33/34 (97%). The negative predictive value was 5/15 (33%) and was interpreted as an expression of the radiologist's cautious assessment. 14/49 (29%) died before March 1990. Poor prognosis was related to invasion of major vessels and was found in 14 patients of whom eight died. It seems established that CAT-scan presents an extremely valuable preoperative investigation when it comes to planning of surgical strategy in a patient population with testicular cancer metastases with difficult access. PMID- 1926600 TI - [Surgery of ruptured abdominal aortic aneurysm. Are the results compatible with the effort?]. AB - During 1979-1988 218 patients were operated on for ruptured abdominal aortic aneurysm. On admission 110 patients (50%) were in shock. Patients with a systolic blood pressure less than 100 mmHg, anuria on admission, peroperative bleeding of more than five litres and aged more than 70 years had an increased mortality. The intraoperative mortality was 15% and the postoperative mortality 21%. The perioperative mortality decreased from 45% in 1979 to 32% in 1988. The most frequent complications were renal failure and respiratory insufficiency, both were associated with a mortality of more than 50%. The five year survival was 48%. This study has revealed that patients with ruptured abdominal aortic aneurysm have an acceptable prognosis. The investigation emphasizes the importance of early diagnosis and elective operation to avoid rupture. PMID- 1926602 TI - [Surgical treatment of forearm fractures]. AB - A retrospective investigation was undertaken on 62 patients with 103 fractures. Of these, 61 fractures were treated with Rush pin, ten with plate osteosynthesis and three with cerclage. Fifty-three patients were followed up. This revealed that 50% of the patients achieved excellent or satisfactory results. 39% did not have satisfactory results while six patients (9.7%) developed pseudoarthrosis and thus unacceptable results. The healing percentage was 92.3 and the infection rate 3.1. These results are considerably better than previously reported series of forearm fractures treated with medullary osteosynthesis and they are comparable with the results of plate osteosynthesis. Rush pin osteosynthesis appears to be as good as plate osteosynthesis but this should be illustrated by means of a controlled investigation. PMID- 1926603 TI - [Prognostic factors in pigmented villonodular synovitis]. AB - By means of the diagnostic register, all of the patients in the County of Funn with the diagnosis pigmented villonodular synovitis (PVS) during the years 1973 to 1987 were localized. Out of 22 patients, 19 were followed-up clinically and radiologically. Fifteen patients had PVS in a knee, 63% were women. The diagnosis was established late. Repeated punctures of the knee with dark aspirate without relevant trauma should raise the suspicion of PVS. The clinical course of the disease could not be related to the radiographic findings or the histology but depended rather on the localization. In some patients, PVS ran a more aggressive course and arthroses were observed electively in patients treated early. The prognosis in cases diagnosed early was not better but, as treatment yielded considerable relief of symptoms, early treatment was considered to be of value. This consists of local resection of the nodular PVS elements and as radical synovectomy as possible in the diffuse cases. Treatment of recurrences should depend on the symptoms and the degree of possible arthrosis. One patient who had had three recurrences received irradiation with good results. Restricted joint mobility after synovectomy is treated effectively with brisement. PMID- 1926604 TI - [Permanent central venous catheters in oncologic patients]. AB - Permanent central venous catheters play an important role in the treatment of patients with malignancies. Two systems are available, Hickman-Broviac Catheters (HB) and Port-a-Cath (PAC), the latter is fully implantable. Since 1982, the systems have been used in the Finsen Institute. In the period 01.01.1984 to 31.03.1988 a total of 232 HB and 52 PAC were inserted in 245 patients with solid malignant tumours with one exception. All the catheters were inserted with the venous cut-down technique and at the end of the period mainly in local analgesia. The total indwelling time was 36,859 days, mean 99 days (1-616 days) for HB and 92 days (8-519 days) for PAC. Seventeen catheters remained in place for more than 365 days. A total of 114 complications concerning 88 catheters were registered. The most serious complications were sepsis and thrombosis. The frequency of sepsis was low, 0.06 (HB) and 0.01 (PAC) per 100 catheter-days. The corresponding frequency of thrombosis was 0.03/100 catheter-days for both systems. Sixty-one HB and five PAC had to be removed because of complications. In general, the complication rate was lower for the PAC method. In addition, the nursing care was reduced to a minimum. The surgical cut-down method is preferable, as catheter implantation is possible even in patients with disorders of the coagulation system. PMID- 1926605 TI - [Consider always tuberculosis. A case of peritoneal tuberculosis]. AB - A case of peritoneal tuberculosis is presented. The possibility of tuberculous infection should always be borne in mind. PMID- 1926606 TI - [A case of pulmonary edema after intravenous administration of iohexol (Omnipaque) 300 mg I/ml in cerebral CT]. AB - A case of acute pulmonary oedema which developed in connection with intravenous administration of a conventional dose of nonionic radio-opaque agent (RKM) prior to computed tomographic scanning of the posterior cranial fossa is presented. The potentially pathogenetic mechanisms of pulmonary oedema induced by radio-opaque agents are discussed. PMID- 1926607 TI - [Occupational carpal tunnel syndrome?]. PMID- 1926608 TI - [Treatment of lung cancer]. PMID- 1926609 TI - [Treatment of staphylococcal infections in general practice]. PMID- 1926610 TI - [Clinical decision support and informatics]. PMID- 1926611 TI - [Observer variation in clinical practice. A review]. AB - Observer variation denotes the discrepancy between two consecutive observations of the same indicant. Principles and results of observer variation studies are outlined. Observer variation seems to be present wherever it is searched for, in history taking as well as in physical examination. It has been found unanimously to be smaller for intra- than for inter- observer variation while it is still controversial whether clinical experience lessens observer variation. Even fundamental clinical observations and particularly evaluations of borderline cases between normal and abnormal exhibit observer variation. The possibilities of reducing observer variation, and the importance of observer variation to clinicians and patients, and also the influence on research and society are referred to briefly. The future role of observer variation studies is discussed. Observer variation often is evaluated by the Kappa statistics whose statistical advantages and clinical disadvantages are outlined. PMID- 1926612 TI - [Computer-assisted respirator treatment of neonates]. AB - A retrospective investigation was undertaken to assess the value of a knowledge based computer programme for improved respirator treatment of neonates in ventilators. On the basis of the arterial gas values from 30 premature infants with birthweights of under 1,500 g and suffering from the respiratory distress syndrome, the alterations in ventilator settings which were made were compared with the suggestions made by the programme. The programme was in agreement with the written instructions in the department. Complete agreement was found between the adjustments actually made and those suggested by the programme in 37.5% and complete or partial agreement in 68% of the infants. Agreement was poorest among the infants who died from respiratory insufficiency or who developed pneumothorax. A frequent cause of defective agreement was that ventilator settings were not adjusted according to the gas values recorded. The sequel of this was most frequently absence of improvement or deterioration in the subsequent gas values. This occurred most frequently during night hours. This investigation reveals that respirator treatment of neonatal infants is difficult and that easily accessible qualified advice is required. PMID- 1926613 TI - [Production of human antimurine antibody after in vivo use of radioisotope labelled murine antibodies]. AB - In vivo employment of monoclonal antibodies of murine origin (MoAb) with the object of immunotherapy or immunoscintigraphy may result in formation of human antimouse antibodies (HAMA) in a number of the persons exposed. HAMA is of IgG and also IgM types. Allergic reactions may occur but only few are of serious nature (less than 0.3 per thousand). In cases where MoAb is administered on repeated occasions, HAMA forms complexes with the injected which results in resuced quality of immunescintigraphic examinations, increased clearance of MoAb and reduced effect of immunetherapy. "Sandwich" type of immune analyses on blood samples which contain HAMA must be planned so that HAMA interference is eliminated. PMID- 1926614 TI - [Violent patients in a psychiatric outpatient department]. AB - During the period 23.11.1987-22.11.1989, a total of 7,906 patients attended the psychiatric outpatient department and observation section on 12,469 occasions. Sixty patients (0.8%) behaved violently on 85 occasions. None of these episodes of violence resulted in injuries to persons requiring medical attention. 90% of the violent patients were men and 70% were in the age group 20-39 years. Approximately 1/5 were psychotic and, of these, approximately half suffered from schizophrenia. Comparison with the non-violent patient revealed that the probability of violence was greater if the patient was a man under the influence of alcohol and who had the diagnoses of narcomania, drug abuse or personality disorders. Significantly fewer violent patients were admitted than non-violent patients. Over 80% of the violent patients had previously been admitted to psychiatric departments. Approximately 60% had behaved violently on previous consultations with the psychiatric outpatient department. PMID- 1926615 TI - [Wernicke-Korsakoff syndrome at the Rikshospitalet in 1979-1988. A retrospective study]. AB - Wernicke encephalopathy and Korsakoff psychosis are two facets of the same disease with well-determined cerebral lesions caused by thiamine deficiency. The disease occurs mainly in alcoholics, but other conditions (malabsorption or severe malnutrition) also predispose to the risk of Wernicke-Korsakoff syndrome. The incidence in Denmark is unknown. In the period 1.1.1979-31.12.1988, 24 patients (18 men and six women) were discharged from Rigshospitalet with the diagnosis Wernicke encephalopathy or Korsakoff psychosis. This represents about 0.05% of all admissions in the period. Eighteen out of the 24 cases (75%) were admitted in the past three years (1986-88). The mean age was 55 years. Twenty patients admitted alcohol abuse. The presenting symptoms and the patients' complaints showed great variety and were often related to other alcoholic complications, which could mask the disease. The classic symptom combination: eye movement abnormalities- ataxia and disorders of consciousness were found in seven patients (29%). Sixteen patients had disorders of consciousness or orientation. All the patients were treated with thiamine. The eye-movement disorder has recovered in eight out of ten known cases (80%), nystagmus--in six out of seven cases (86%) while ataxia, disorders of orientation and confabulation recovered in about 50% of cases. The average duration of hospitalisation was 50 days. Altogether nine patients died during the observation period. The condition is most probably underdiagnosed and the traditional diagnostic criteria are considered too rigid. The diagnosis should be considered in alcoholics who present even only one of the classical symptoms and in patients with alcohol dementia. Thiamine should be given on wide indications. PMID- 1926616 TI - [Psychotherapy of patients with schizophrenia. Study of the significance of group supervision]. AB - A Danish centre contributed 12 cases to a Nordic multicentre investigation concerning the psychotherapy of psychoses. Patients admitted consecutively to the psychiatric hospital with the diagnoses of schizophrenia, schizophreniform psychosis or schizoaffective psychosis were offered psychotherapy at least once weekly for two years in addition to the other treatment modalities administered. In the Danish design, the process of supervision in relation to the processes of psychotherapy was investigated. In the present article, examples are presented illustrating how core psychotic mechanisms in the patients are reflected not only in process-facilitating but also in process inhibiting psychotherapeutic interventions. The data of the investigation are these interventions which are written down prospectively in the summaries of the supervision. PMID- 1926617 TI - [Treatment of cardiac arrest in general practice. A prospective study]. AB - Since 1978, all of the ambulance stations in South Jutland have been equipped with defibrillators, equipment for intubation, drop equipment, infusion fluids and medicaments for treatment of acute medical and surgical emergencies. In 1989, a prospective investigation was undertaken of the results of the treatment of cardiac arrest outside hospital and carried out by general practitioners in cooperation with the ambulance staff or the ambulance staff alone. The investigation revealed that four out of 11 patients with cardiac arrest survived in the group treated by doctors and ambulance staff in the pre-hospital phase while only one out of 22 patients were resuscitated by the ambulance staff alone. As assessed by the clinical investigation, none of the surviving patients had sequelae of cardiac arrest. In addition, treatment in the ambulance proved life saving for two patients with acute myocardial infarction and pulmonary oedema who were unconscious on account of the pulmonary oedema. The investigation shows the importance of pre-hospital treatment for survival and, in sparsely populated regions far from hospitals, it is essential that this treatment is carried out by general practitioners as the time-factor is decisive for the survival of the patient. PMID- 1926618 TI - [Cesarean section. Changes in frequency and indications in the county of South Jutland during a 10-year period]. AB - During recent years, the frequency of Caesarean section has changed everywhere. Changes during a ten-year period in the Department of Gynaecology in Sonderborg Hospital were registered and involve mainly the groups of imminant foetal death, previous Caesarean section, foeto-pelvic disproportion and placental insufficiency. Alterations in the obstetric services in the County of South Jutland and improved neonatal service have played an important part in development of the frequency of Caesarean section of Sonderborg Hospital. PMID- 1926619 TI - [The significance of brain death as a criterion for renal transplantation. Status after 9 months]. AB - The effect of introduction of the brain-death criterion in Denmark on the course of cadaver kidney transplantation was evaluated by comparing the course of 31 consecutive patients transplanted after introduction of brain-death criterion with the course of a similar consecutive group of patients transplanted just before the new death criterion. The consequences of the new death criterion were significantly earlier onset of graft function, diminished need for posttransplant dialyses, reduced need for immunosuppressive treatment with Minnesota antilymphocytglobulin and briefer hospital stays. The easier postoperative course had great psychological effects for the patients and the staff, and the cost of each transplantation was estimated to be reduced by at least 50,000 DKr per patient (approximately 5,000 pounds). PMID- 1926621 TI - [Reversible regional myocardial ischemia in variant angina]. AB - A case of severe ventricular ischaemia induced by hyperventilation which occurred in a woman aged 44 years is presented. The ischaemia was confirmed by echocardiography and scintigraphy and coronary arteriography revealed spasm in the proximal segment of the anterior descending branch of the left coronary artery. PMID- 1926620 TI - [Adult Gaucher's disease with pulmonary involvement]. AB - Gaucher's disease is an autosomal recessive disorder caused by deficiency of the enzyme glucocerebrosidase with accumulation of glucocerebroside in the reticuloendothelial system. Affection of the lungs by this disease is extremely rare. When Gaucher cells infiltrate the lung, fibrosis may result. We describe a case with adult type Gaucher's disease who, besides affection of liver, spleen and bone marrow, had severe pulmonary involvement with extensive interstitial fibrosis, increased pulmonary vascular resistance, and pronounced reduction in diffusion capacity. PMID- 1926623 TI - [Histiocytic necrotizing lymphadenitis (Kikuchi's disease)]. AB - We report a typical case of histiocytic necrotizing lymphadenitis (Kikuchi's disease). To our knowledge this is the first reported case in Denmark. Histiocytic necrotizing lymphadenitis is a benign self-limiting disorder, which mainly involves the cervical lymph nodes. The disease commonly affects young women of Asian origin, but it is seen more and more often in other populations. Clinically and histologically it can be misdiagnosed as malignant lymphoma. The etiology is unknown. PMID- 1926622 TI - [A case of perforation of a blind loop secondary to ileocolic side-to-side anastomosis]. AB - A rare late complication of side-to-side anastomosis; perforation of a blind loop with subsequent localized inflammation of the abdominal wall is presented. Operative intervention with resection of the blind loop and the establishment of an end-to-end anastomosis is recommended. PMID- 1926624 TI - [Systems for clinical decision support: a terminological mini-Baedecker]. PMID- 1926625 TI - [Research or journalism]. PMID- 1926626 TI - [Meta-analysis]. PMID- 1926627 TI - [An analysis of a selected Danish meta-analysis]. PMID- 1926628 TI - [Supplementary technical comments on a meta-analysis of the effect of salt restriction on blood pressure]. PMID- 1926629 TI - [Diagnosis of brain injuries--one more time]. PMID- 1926630 TI - [The earth is not flat]. PMID- 1926631 TI - [Amalgam--polyuria]. PMID- 1926632 TI - [Mometasone furoate]. PMID- 1926633 TI - Biological structures imaged in a hybrid scanning transmission electron microscope and scanning tunneling microscope. AB - A hybrid scanning transmission electron microscope (STEM) and scanning tunneling microscope (STM) is described which allows simultaneous imaging of biological structures adsorbed to electron-transparent specimen supports in both modes of scanning microscopy, as demonstrated on uncoated phage T4 polyheads. We further discuss the reproducibility and validity of height data obtained from STM topographs of biomacromolecules and present raw data from topographs of freeze dried, metal-coated nuclear envelopes from Xenopus laevis oocytes. PMID- 1926634 TI - Improved transfer of two-dimensional crystals from the air/water interface to specimen support grids for high-resolution analysis by electron microscopy. AB - Electron crystallographic analysis of two-dimensional crystals grown on lipid layers at the air/water interface has been limited by loss or damage during transfer of the crystals to an electron microscope support grid. Two methods of transfer are described which are applicable on a small scale (10 microliters of protein solution) and which give greatly improved results for streptavidin crystals on biotinylated lipid layers. In the first method, a hydrophobic grid surface was produced by coating a carbon support film with a thin layer of SiO2, followed by alkylation with dimethyloctadecylchlorosilane. The transfer efficiency of protein crystals approached 50% coverage of the alkylated grid surface. The degree of order of crystals transferred to the alkylated grid surface and preserved in negative stain was significantly improved over that of crystals transferred directly to a carbon support film. In the second method, crystals at the air/water interface were transferred to a holey carbon support film. The efficiency of transfer across the holes was virtually 100% as nearly every hole was completely covered with crystals. After preservation of the crystals in 1% glucose and cooling to liquid nitrogen temperature, electron diffraction was obtained that extended to 1/2.8 A-1 resolution. This demonstrates that two-dimensional crystals grown on lipid layers at the air/water interface can be sufficiently well-ordered, even after transfer to a support grid, to yield high-resolution structural information. PMID- 1926635 TI - Temperature directly affects the rate of irradiation-induced mass loss from phosphatidylcholine multilayers. AB - We monitored the mass thickness of egg yolk phosphatidylcholine multilayers at several temperatures during electron irradiation. The rate of irradiation-induced mass loss was reduced substantially when this specimen was cooled to liquid nitrogen temperature from room temperature. Additional cooling to liquid helium temperature caused an additional reduction of mass-loss rate. The characteristic doses D(1/e), which are the slopes of the logarithm of the differential mass thickness against dose, were approximately 7 x 10(3) e/nm2 at 290 K, 8 x 10(4) e/nm2 at 130 K, and 1.4 x 10(5) e/nm2 at less than 10 K. The fractions of the original mass thickness that remained after arbitrarily high doses were about 69% at 290 K, 72% at 130 K, and 77% at less than 10 K. PMID- 1926636 TI - Urologic malignancies: quality of life issues. PMID- 1926637 TI - Quality of life: how is it measured and defined? AB - Quality of life is an abstract concept which encompasses an individual's perceived level of physical, psychological, and social well-being. It is a highly subjective phenomenon, mediated by one's personal and cultural values and beliefs, self-concept, goals, and life experiences. Some studies have demonstrated that an individual's quality of life may be influenced negatively by a diagnosis of cancer and/or the sequelae of treatment. Concerns about quality of life issues may affect a patient's choice of treatment options or compliance with treatment regimens. Although there is no universally agreed-upon instrument to measure quality of life, researchers are increasingly utilizing multidimensional patient self-assessment tools in lieu of physician-rated performance status scales. Recent advances in detection and treatment may improve quality of life for patients with urologic malignancies. Cancer treatment which extends quantity while maintaining or improving quality of life is the mandate of care for the future. PMID- 1926639 TI - Impotence after radical pelvic surgery: physiology and management. AB - Impotence has been a common problem after radical surgery of the colon, rectum, prostate, bladder, and seminal vesicle. However, a better understanding of the neuroanatomy of erection has resulted in its decline. When impotence does result, in cases where the extent of tumor involvement renders preservation of the neurovascular bundle impossible, the variety of treatments available is now improved: these include intracavernous injection of vasodilators, vacuum constriction devices, penile arterial and venous surgery, and penile prostheses. The improved understanding and management of impotence has greatly enhanced the quality of life of patients after radical pelvic surgery. PMID- 1926638 TI - Pain management for urological malignancies. AB - Three ways to treat pain from malignancy include modifying the source of pain, interrupting transmission of pain, or altering the perception of pain. This review will discuss agents or techniques used for cancer pain relief through interrupting transmission and altering the perception of pain. Agents or techniques discussed include nonnarcotic analgesics, antidepressants, anticonvulsants, anesthetic and neurosurgical procedures. PMID- 1926640 TI - Nerve sparing and continence preservation during radical prostatectomy. AB - Prostate cancer is one of the most common malignancies occurring in men. During the last decade, several advances have been made in decreasing the morbidity of surgical therapy. Two major advances have included an improved understanding of the physiology of erection and anatomy of pelvic parasympathetic nerves mediating erectile function. Surgical techniques of 'nerve preservation' during surgery can preserve postoperative potency in 50-70% of patients with localized prostate cancer. In others the use of intracorporal vasoactive agents, vacuum suction devices and surgical techniques can additionally improve potency. Knowledge of the various mechanisms contributing to continence have additionally enabled modifications in surgical techniques to enhance continence rates postoperatively. Currently postoperative continence after radical prostatectomy occurs in over 95% of patients. PMID- 1926641 TI - The value of screening for prostatic carcinoma: a commentary. AB - Can routine digital rectal examinations, transrectal ultrasound studies, and prostate-specific antigen determinations reduce deaths from prostatic carcinoma? The evidence is that the benefits of early diagnosis and treatment are at least neutralized by the limited reliability and high monetary and human costs of the test and by the lack of proof that treatment is effective for those tumors detected. One must conclude that universal screening is not now warranted and will await demonstration of effectiveness by controlled studies. PMID- 1926642 TI - Organ preservation in the management of pelvic rhabdomyosarcoma. AB - The role of exenterative surgical therapy in pelvic rhabdomyosarcoma has been progressively diminishing with the increasing effectiveness of combination chemotherapy. Cooperative studies have demonstrated that, in most instances, the initial surgical procedure should consist of a thorough examination under anesthesia and a biopsy of the mass. Surgery should be repeated to evaluate the therapeutic response to chemotherapy (with or without radiation treatment) so that radical resection, when necessary, is not unduly delayed. In some instances, patients who responded only partially to treatment will, with limited surgical excision, demonstrate a complete response on pathologic examination. The late effects of this multidisciplinary treatment plan must be studied further and long term follow-up for these children is imperative. PMID- 1926643 TI - Use of the ileocecal segment for bladder substitution or continent urinary diversion. AB - Urinary reservoirs constructed from the ileocecal segment conform generally to the principles of an ideal bladder substitute. They have psychological and functional advantages for selected patients who require urinary diversion. The reservoir can easily be placed in the pelvis attached to the urethra. Alternatively, an extremely efficient efferent continence mechanism that is both easy to catheterize and to construct can be made from tapered terminal ileum and an intact ileocecal valve. PMID- 1926644 TI - Use of biological response modifiers for management of renal cell carcinoma. AB - The approach to the treatment of patients with metastatic renal cell carcinoma has changed dramatically during the past 5 years. In the past, efforts to treat metastatic renal cell carcinoma were directed at palliation using chemotherapy, hormonal agents, or radiation therapy to control symptoms. Metastatic renal cell cancer was often resistant to these agents. With the advent of biological response modifiers, an entirely different approach is now available. Both recombinant human interferon-alpha (IFA-alpha) and interleukin-2 (IL-2) have significant activity in advanced renal cell carcinoma. Treatment with IFN-alpha can be given as outpatient therapy and provides effective disease control in a substantial minority of cases. Treatment with IL-2-based therapy, although associated with significant acute toxicity, is capable of inducing durable remissions from this otherwise lethal disease. PMID- 1926645 TI - Endopyelotomy for treatment of ureteropelvic junction obstruction. AB - A total of 14 patients underwent endopyelotomy at our institution for treating ureteropelvic junction (UPJ) obstruction (12 primary and 2 secondary obstructions) between March 1986 and July 1989. Radiographic evaluation of the patients with a minimum follow-up of 6 months demonstrated improvement in 11, while the remaining 3 were stable. These 3 were cases with primary obstruction and 2 of them had had an associated large redundant renal pelvis. No patients exhibited evidence of increased hydronephrosis or decreased renal function. Twelve of the 14 patients had had preoperative symptoms. Complete and partial remission of the symptoms was obtained in 11 and in 1 who was radiographically stable, respectively. Thus, our success rate for endopyelotomy was 75% in primary obstruction. Successful results were obtained in all the 2 cases with secondary obstruction. There was 1 patient with an intraoperative complication (extravasation) and a late complication related to the stent. However, the problems were minor and easily corrected. Our results suggest that careful selection of cases may lead to a high success rate in endopyelotomy for treating primary UPJ obstruction. PMID- 1926646 TI - In vivo measurement of force in the ureter. 2. Influence of urinary flow. AB - By means of a newly developed measuring catheter the occluding force of the ureter under changing diuresis conditions was investigated using 12 canine ureters. Even under extremely high flow rates of some 50 times normal values, the ureter returned after short phases of noncoaptive transport to active bolus transport. No direct connection between flow rate and basal pressure on the one hand and the form of transport on the other hand was observable. Only after prolonged continuous loading on the ureter with high flow rates was a loss of occluding forces observed with the noncoaptive form of transport, then taking on more significance. PMID- 1926647 TI - 25 years of experience in the reconstruction of the efferent urinary tract with ileum. AB - All sections of the efferent urinary tract can be replaced by a transposed ileum segment. Our surgical procedure and postoperative results are reported. PMID- 1926648 TI - Urethrorectal fistulas complicated by posterior urethral stricture: an appraisal of management by transpubic approach. AB - Seven cases of difficult urethrorectal fistulas complicated by posterior urethral stricture following accidental trauma were repaired successfully by a transpubic approach. This method makes urethroplasty of complex posterior urethral stricture, closure of urethrorectal fistulas and an omental interposition possible. This approach was considered after a review of all techniques described to treat the urethrorectal fistulas. PMID- 1926649 TI - Male urethral calculi. AB - Male urethral stone is a rare clinical entity in western parts of the world, but continues to be common in developing countries. We report 26 cases of male urethral calculi, treated over a 6-year period. The age of the patients ranged from 12 to 67 years. The calculi were encountered all along the urethra, but predominantly in the posterior urethral region. We found multiple stones in 6 cases and large giant calculi in 5. Presentation, etiology, treatment, and prevention of these calculi are discussed. PMID- 1926650 TI - Significance of the intracavernosal pharmacological injection test, pharmacocavernosography, artificial erection and cavernosometry in the diagnosis of venous leakage. AB - 149 men suffering from erectile failure underwent a standardized combined procedure including intracavernosal pharmacological injection test (P test) artificial erection, pharmacocavernosography and cavernosometry with analysis of intracavernosal erection pressure and pressure drop. Patients with negative P test were considered to be suffering from 'venous leakage'; data of cavernosography and cavernosometry were analyzed in relation to the results of the P test. 99 men (66.4%) were P-test-negative. 98 of these patients (99%) had pathological cavernous drainage of the plexus santorinii during cavernosography. Flow rates for induction and maintenance of erection of the P-test-negative men were increased and intracavernosal erection pressure decreased significantly compared to the P-test-positive patients. The very diversified range of values made any individual statement impossible. In contrast to these findings, duration of pressure drop was significantly shorter among men with suspicion of venous leakage and without any overlapping compared to P-test-positive men. The findings provide evidence for the necessity, besides pharmacocavernosography, to include an estimation of intracavernosal pressure drop time in the diagnostic procedure of venous leakage in all men with confirmed negative P test. PMID- 1926651 TI - Single-dose fosfomycin trometamol (Monuril) versus multiple-dose norfloxacin: results of a multicenter study in females with uncomplicated lower urinary tract infections. AB - The results of an open, randomized study comparing the efficacy and safety of Fosfomycin trometamol (Monuril), 3-gram single dose, and Norfloxacin (Noroxine 400), 400 mg twice daily for 5 days, are reported. Clinical and bacteriological assessments were performed before and 3-4 (short-term) and 25-30 days (long-term) after treatment. Only female patients with uncomplicated lower urinary tract infection were eligible for inclusion in the study: 33 cases were given Fosfomycin trometamol and 30 cases Norfloxacin. In the overall etiology, Escherichia coli (74% of the strains found), Proteus mirabilis (6%) and Klebsiella pneumoniae (6%) are highly predominant. With regard to bacteriological efficacy, the percentages of eradication in the two groups were similar: after the short-term test, 93.9% (31 of 33 patients) in the Fosfomycin trometamol group and 86.6% (26 of 30) in the Norfloxacin group, and after the long-term tests, 73.3% (22 of 30) in the Fosfomycin trometamol group and 77.89% (21 of 27) in the Norfloxacin group. There are no statistically significant differences. The duration of the reported side effects was significantly lower in the Fosfomycin trometamol group. The simplified dosage regimen (single dose) and its favorable benefit/risk ratio justifies the use of Fosfomycin trometamol as a treatment for uncomplicated urinary tract infections in female patients. PMID- 1926652 TI - Evaluation with MR imaging of leiomyoma of the bladder. PMID- 1926653 TI - Benign mixed mesenchymal tumor of the spermatic cord. AB - We report a case of benign mixed mesenchymal tumor consisting of spindle cells and an area involving osseous elements. Immunohistochemical investigation revealed the spindle tumor cells to express vimentin and the alpha-subunit of S100 protein, but no staining for other specific antigens. The findings thus suggest that the spindle tumor cells are undifferentiated in nature and derived from mesenchyma, the osseous component being interpreted as evidence of a specific differentiation. PMID- 1926654 TI - Growth and metastasis of human bladder cancer xenografts in the bladder of nude rats. A model for intravesical radioimmunotherapy. AB - A potentially useful therapeutic approach to the treatment of human bladder cancer is intravesical therapy with radiolabelled monoclonal antibodies (MAbs). We have established an animal model to study this approach. Inoculation of cloned 2B8 cells derived from the human bladder cancer cell line, UCRU-BL-17, into the bladder wall of nude rats pre-irradiated with 900 rads, resulted in local tumour growth in 39/40 (97.5%) animals, with invasion or metastases to distant organs in 25% of cases. Both the bladder tumours and the metastases were morphologically similar to the original biopsy sample from which the cell line, UCRU-BL-17, was established. The cells were of human origin, as shown by expression of HLA antigens, Alu probing, and cytogenetic analysis. Preliminary studies indicated that i.p. injection of anti-human bladder cancer monoclonal antibody (MAb), BLCA 38, radiolabelled with either iodine 131 or samarium 153 (153Sm), resulted in tumour localisation, with tumour-to-blood ratios of 5.04 (131I), and 4.3 and 3.1 (153Sm) respectively. We now aim to examine the efficacy of the intravesical route for radioimmunotherapy in the nude rat model. This model will also serve for preclinical studies on the efficacy of systemically injected radioimmunoconjugates for control of metastatic growth. PMID- 1926655 TI - Growth fraction of human bladder tumors. AB - The growth fraction of bladder tumors was immunohistochemically assessed in situ using anti-DNA polymerase (Pol alpha) monoclonal antibody. This enzyme is known to be present in the nucleus of the cells in G1, S, and G2 phases. The percentage of labeled cells was expressed as the labeling index (LI). The average LI was 6.0% in normal epithelium and 17.8% in bladder tumors, this difference being significant. The labeled cells were distributed throughout both the basal and surface layers of bladder tumors. However, in some bladder tumors, the distribution of Pol alpha-labeled cells varied from area to area. The higher fraction of labeled cells was found in high grade or invasive tumors. Papillary and nodular bladder tumors showed a greater rate of cell proliferation than papillary tumors. These findings suggest that Pol alpha immunostaining could be a potent tool for easy and quick evaluation of proliferating cells in bladder tumors, thereby providing a supplement to conventional histological findings. PMID- 1926656 TI - Characterization of peripheral blood T-cell subpopulation of bladder cancer patients. AB - The levels of immune reactivity of peripheral and blood T-lymphocytes were evaluated in 37 bladder cancer patients and 31 age-matched controls. T-lymphocyte subsets were quantified by monoclonal antibodies, and the immune reactivity was measured using stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM). Comparing the patients before and after treatment revealed significant changes in the stimulation index of proliferative response to PHA, PWM, in the PWM% (the patient response compared to the control), and in the percent of T8 cells from the total count of blood lymphocytes. Further significant differences were found among the disease stages in the numbers of T3, T4 lymphocytes subpopulations and the total lymphocyte count. A significant interaction was found between the treatment and patient's sex regarding the T4:T8 ratio. Also, a higher prevalence of T4:T8 less than 1 was found among the patients compared to the controls before and after treatment regardless of the disease stage. This T4:T8 less than 1 ratio can serve as an indicator of immune competence in bladder transitional cell carcinoma patients. PMID- 1926657 TI - Chlamydia trachomatis antigen can be detected in the urine sample of men with non gonococcal urethritis. AB - We tested the first portion of voided urine (FVU) and urethral swab from 80 patients with non-gonococcal urethritis (NGU) using a novel enzyme-amplified immunoassay (IDEIA) for the detection of Chlamydia trachomatis antigen. Urine specimens were positive in all patients with positive urethral swabs (positive coincidence ratio, 100%) and in 6 of 54 patients with negative swabs (negative coincidence ratio, 88.9%). Our data suggest that FVU is suitable for the detection of Chlamydia trachomatis antigen using the IDEIA test in patients with NGU. PMID- 1926658 TI - Long-term treatment of nocturnal enuresis with desmopressin. A follow-up study. AB - Eight patients with monosymptomatic nocturnal enuresis (age 11-24 years) were investigated prior to and after 24 weeks of desmopressin treatment in order to evaluate the impact on the endogenous vasopressin secretion and urinary output. No effect on plasma vasopressin, diurnal urinary volume, and urinary osmolality were found after this long-term treatment. Overall no changes in either body weight, blood pressure, or hematological variables were demonstrated. This supports previous findings that the treatment appears to be well tolerated and free of side effects in longer term. PMID- 1926659 TI - How to measure urethral elastance in a simple way. Elastance: definition, determination and implications. AB - The elastance of a biological tube describes the resistance of the latter to dilatation. It is defined as dP/dV, where dP is the pressure increase caused by the volume increase dV. Elastance is the reciprocal of compliance. Elastance in the female urethra can be estimated from the slope of the regression line of related values of pressure and cross-sectional area. In the present study, urethral elastance was calculated by measurement of the related pressures and cross-sectional areas during stepwise dilatation by a balloon and by determination of the pressure at which inflow through side holes in catheters with increasing diameters began. There was no difference between the elastance values obtained by the two methods. Due to the linear correlation found between pressure and cross-sectional area we conclude that urethral elastance can be estimated from measurements of urethral pressure at two or more related cross sectional areas by a simple technique using e.g., 8F, 14F, and 20F catheters. PMID- 1926660 TI - Decreased absorption of 22Na and 36Cl in ileal reservoirs after exposure to urine. An experimental study in patients with continent ileal reservoirs for urinary or fecal diversion. AB - After urinary diversion to intestinal segments, reabsorption of chloride, ammonium, and hydrogen ions occurs, sometimes leading to hyperchloremic acidosis. The mucosa of ileal reservoirs exposed to urine show substantial atrophy, indicating a loss of absorptive capacity. In ten patients with urinary diversion via a continent ileal reservoir, the absorption of [22Na] and [36Cl] was studied after instillation for 15 min into the reservoir of a test solution containing 50 kBq [22Na] and 50 kBq [36Cl]. The activity of the radionuclides was determined in serum samples after 60 and 180 min and the fractions absorbed were calculated. Absorption of the two radionuclides was also calculated by comparison of the activities in samples of the test solution taken before and 15 min after instillation into the reservoir. The same investigations were performed in seven patients with continent ileostomy reservoirs. The study demonstrated a decreased capacity to absorb [22Na] and [36Cl] across the mucosa of the reservoirs exposed to urine compared to the mucosa of those exposed to feces. Due to the transformation of the ileal mucosa after exposure to urine, the risk for development of metabolic disturbances should be minimal after urinary diversion to a continent ileal reservoir. PMID- 1926661 TI - CO2 and Nd:YAG laser systems in microsurgical venous anastomoses. AB - A comparative study was undertaken in 81 rats to investigate a CO2 and Nd:YAG laser system for laser-welded anastomosis of the femoral vein. Conventionally sutured anastomoses (CMSA) served as controls. Laser-welded anastomosis (LAMA) was easier and could be performed 30% faster than CMSA. Postoperative investigations included patency tests, postmortem examinations and light and electron microscopy. Aneurysms were not seen. Foreign-body reaction was more pronounced in CMSA. Patency rates for CO2-LAMA and CMSA were equal, whereas Nd:YAG-LAMA resulted in significantly higher rate of early postoperative thrombosis (P less than 0.01). Because of its physical properties, the CO2-laser system seems to be better suited for laser welding of delicate structures such as the rat femoral vein. PMID- 1926662 TI - Changes in regional renal perfusion following ischemia/reperfusion injury to the rat kidney. AB - Post-ischemic renal failure is associated with a zone of vascular hyperaemia in the outer medulla of the kidney. The effect of this lesion on regional renal perfusion is, however, unclear. Acute unilateral renal ischemia was applied to four groups of ten adult male Wistar rats for a period of 60 min, followed by revascularisation for 0, 15, 30 or 60 min. The aorta was then clamped and Microfil was injected at a standard pressure to fill the renal vasculature. Gross and histological examinations of the renal parenchyma and vasculature were then performed. Regional renal Microfil perfusion was quantified by examination of unstained histological sections, giving rise to a vascular perfusion index (VPI) for each vascular region of the kidney. The VPIs were similar in control and ischemic kidneys that were not subjected to reflow (group 1). In contrast, the VPI was markedly decreased in the inner stripe and inner medulla in animals in which revascularisation had occurred (groups 2-4), and the vasculature in these regions was histologically shown to be packed with red blood cells. Post-ischemic renal failure is associated with hyperperfusion of the medulla resulting from blockage of the vasculature that occurs during revascularisation. PMID- 1926663 TI - Toxicity of litholytic ethylenediaminetetraacetic acid solutions to the urothelium of the rat and dog. AB - The toxicity to the urothelium of bipotassium ethylene-diaminetetraacetic acid (K2-EDTA) buffered with 0.2 M triethanolamine (TEA) at pH 8 and 8.5 was tested in rats and dogs. Even at a low concentration of 3.125 mM, K2-EDTA is very noxious to the bladder mucosa. This toxicity is not due to the buffer TEA, which is well tolerated. Although buffered K2-EDTA, at pH 8.5 is an excellent chemolytic agent for calcium-containing stones, its clinical use is limited by this toxicity. PMID- 1926664 TI - [Nuclear medicine examination procedures in urology. Part 2]. PMID- 1926665 TI - [Urinary urgency and reflex incontinence]. AB - Urge and reflex incontinence are caused by detrusor dysfunction:urgency may be due to hyperactivity or hypersensitivity of the bladder. Neurogenic hyperactivity of the detrusor is called detrusor hyperreflexia: the neurogenic uninhibited bladder is caused by incomplete, and the so-called reflex bladder by complete, suprasacral lesions. The pathophysiology of symptomatic and idiopathic detrusor hyperactivity and the therapeutic armentarium are described. Bladder drill together with biofeedback and pharmacotherapy with spasmolytic drugs - several potent spasmolytic drugs with different modes of action are available - are the basis of treatment for hyperactivity and hypersensitivity of the detrusor. An alternative is electrostimulation: stimulation of the afferents of the pudendal nerve, via the pelvic floor (anal, vaginal), percutaneously (dorsal nerve of the penis, clitoric nerve) or by the implantation of electrodes results in inhibition of the detrusor. Most (80-90%) patients can be treated successfully by conservative means. Operative measurements comprise bladder denervation and bladder augmentation. The results of bladder denervation by transtrigonal phenolization of the pelvic plexus are highly controversial. In patients with uncontrollable hyperactivity of the detrusor, augmentation of the bladder (e.g. clam ileocystoplasty) is the method of choice, while for those with uncontrollable hypersensitivity of the detrusor, cystectomy followed by bladder substitution should be performed as a last resort. Treatment for urinary incontinence due to detrusor hyperreflexia must be selected bearing in mind that bladder emptying is inadequate, in most cases because of dyssynergia between detrusor and external sphincter. Therapy is basically aimed at transforming hyperreflexia of the detrusor into hyporeflexia, primarily by potent spasmolytic drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1926666 TI - [Surgical therapy of urinary incontinence in the male]. AB - From 1973 to 1990 a total of 340 male patients suffering from incontinence of various etiologies were treated by implantation of an artificial urinary sphincter. In 165 patients the sphincter was placed at the bladder neck, while 175 needed an implantation at the bulbous urethra. Because of the better results with regard to continence, we prefer the bladder neck implantation. The youngest patient treated was 12 years old and the oldest, 91. Most of the patients were between 40 and 80 years old. The highest continence rates were achieved in patients with postprostatectomy urinary incontinence. Among those with a bladder neck implant continence was achieved in 93.3% of all cases, while 87.4% of those with an artificial sphincter at the bulbous urethra achieved continence. The mechanical complication rate was low with 7.05%, whereas tissue-related complications occurred in a total of 25.3% of cases. Revision was necessary in 30.9% of cases during the first few years after implantation; it was striking that the incidence of revision fell dramatically 1 year after implantation. This is also true for any second revision, which usually becomes necessary within the first year after the first revision. In total, however, two-thirds of the patients do not require revision during the first 5 years. These data show that the implantation of an artificial sphincter is the safest and most successful method for the treatment of urinary incontinence in the male. This method is superior to all other operative treatments and should be considered the first line treatment, especially in post-prostatectomy urinary incontinence. PMID- 1926667 TI - [Faulty voiding and drinking habits--a contribution to the genesis of enuretic syndrome?]. AB - In 122 children (85 girls, 37 boys) with nocturnal enuresis, information on drinking and voiding patterns was elicited. Many of them (60% of the girls and 40% of the boys) had previously been continent for 1-5 years. It turned out that the children tried to suppress voiding and had the habit of drinking primarily during the second half of the day. After changing these habits, 119 children became permanently continent. PMID- 1926668 TI - [Urinary incontinence in old age]. AB - Incontinence with onset in old age is due mainly to neurological factors, and in men to the presence of prostatic hypertrophy. Quite often, it is a combination of several different diseases that leads to urinary incontinence. A simple examination schedule suffices for a diagnosis in 90% of all cases. The examination schedule is presented. In the case of a non-inhibited neurogenic bladder, continence training is the most important therapeutic measure. However, various criteria must be observed if continence training is to be successful. The second most frequent cause of incontinence in women is a noncontractile muscle acontractility in the presence of diabetes mellitus. Suprapubic urinary puncture has considerable advantages over transurethral urinary diversion. PMID- 1926669 TI - Female stress incontinence. Treatment options and indications. AB - The diagnosis of urethral sphincter incompetence is confirmed by urodynamic studies which essentially involved twin channel subtracted cystometry. Detrusor instability and voiding difficulty must be detected. The indications for and an outline of conservative treatment are reviewed. The indications for surgery and a brief review of the operations and how they work and the management of recurrent incontinence are reviewed. PMID- 1926670 TI - [Systemic alpha-interferon therapy: a possible method for prevention of testicular atrophy and permanent sterility in patients with bilateral mumps orchitis]. AB - In postpubertal men orchitis is the most common complication of mumps infection, occurring in 5-37% of this population. A bilateral manifestation is observed in 16-65%. The most important danger is the risk of developing testicular atrophy, which results in sterility. Four patients with bilateral mumps orchitis received systemic treatment with interferon-alpha 2B (3 X 10(6) IU/day) for 7 days. All acute symptoms of mumps orchitis disappeared within 2 or 4 days of hospitalization. During 12-20 months of follow-up no incidence of testicular atrophy was observed. In three of the four patients pretreatment examination revealed subfertility (oligoasthenozoospermia), while 2-4 months after interferon treatment and throughout the entire follow-up period normozoospermia was found. No severe adverse effects occurred during treatment. The flu-like symptoms could be prevented by concomitant administration of paracetamol (3 X 500 mg/day). Systemic treatment with interferon-alpha 2B appears to be highly effective in preventing sterility and testicular atrophy after bilateral mumps orchitis. Further investigations involving larger populations should be performed to confirm the present promising results. PMID- 1926671 TI - [Microsurgical, neuroprotective plaque isolation in plastic penile induration]. AB - Conservative therapy of Peyronie's disease has not given very encouraging results. This means operative treatment strategies are the only effective therapy form that appears to be successful. Another treatment form, which often leads to a non-acceptable shorting of the penis, is the technique used in the Schroder Essed and Nesbit procedures. Removal of the plaque, followed by a tissue transplant to cover the excision area, enables a correction of the deviation and maintenance of the original length of the penis. Because of the periodically described, possibly fatal results of postoperative perception disorders of the glans penis, preparation of the dorsal neurovascular bundle is performed under microsurgical conditions. Because of the certainty with which optical identification of nerves and vessels is achieved, it is possible to keep the nerves protected and to have atraumatic isolation of the plaque. After the first encouraging surgical results, we present the operative procedure under microsurgical conditions. PMID- 1926672 TI - [Multicystic renal oncocytoma]. AB - The cystic variant of renal oncocytoma was defined by Ogden et al. (1986), who described a single case. A further case is described in the present communication, with notes on the clinical presentation, aspiration cytology, and histology of the surgical specimen. Follow-up over 3 years has been uneventful. PMID- 1926673 TI - [Post-ischemia normal function of living related kidney transplants after preservation with HTK solution]. AB - This study reports on the first clinical use of HTK preservation solution devised by Bretschneider in renal transplantation. Using this HTK solution, nine living related donor kidneys subjected to cold ischemia for up to 4 h were consecutively transplanted between 1987 and 1989. The postoperative function of the donor and recipient kidneys is analyzed. The endogenous creatinine clearance and the plasma creatinine level are used as function parameters. Within 24-48 h after transplantation a postischemic normal graft function occurred. With triple drug therapy the transplanted kidneys showed an increase in renal function identical with that in the donor's single remaining kidney. Within 7 postoperative days no perfusion damage and no HTK or CyA nephrotoxicity was observed. PMID- 1926674 TI - [High-dose trospium chloride in therapy of detrusor hyperreflexia]. AB - The efficacy and tolerance of a high-dose treatment with trospium chloride (20 mg twice daily) were investigated in pilot studies carried out in three trial centres and involving a total of 29 patients suffering from reflex bladder due to transverse lesions of the spinal cord with paraplegia. In all three centres the trial procedure was the same. Urodynamic measurements (maximum bladder capacity, bladder compliance, maximum detrusor pressure during micturition, urinary flow and residual urine) were taken both before and after treatment with trospium chloride for a period of at least 2 weeks. In almost all patients there was a clear rise in maximum bladder capacity, a marked decrease in maximum detrusor pressure and an increase in bladder compliance. As a result the frequency of micturitions was lowered. In the majority of patients, urinary incontinence caused by detrusor hyperreflexia was brought under control through depression of detrusor activity, and urinary continence was achieved. If necessary, intermittent catheterization was continued to empty the bladder. Tolerance of the test preparation was good, and side-effects were rare and mild. PMID- 1926675 TI - [Early results of endoscopic treatment of vesico-ureteral reflux in children]. AB - Endoscopic treatment of vesicoureteral reflux (VUR) is based on transurethral injection of Teflon paste or collagen gel into the submucosa of the bladder wall beneath the distal ureter, resulting in support of the intramural part. This endoscopic procedure was performed in 75 children with VUR of varying severity. Altogether 111 ureters were treated, 94 with injections of Teflon paste and 17 with collagen gel. Improvement of VUR in the early postoperative period was achieved in 91.5% of the ureters treated with Teflon and in 82.4% of the ureters treated with collagen. No complications were observed. Endoscopic treatment of VUR seems to be an worthwhile alternative to open surgery. However, since long term follow-up has not been completed, the efficacy of the method cannot yet be finally assessed. PMID- 1926676 TI - [Venous leakage--a new therapeutic concept]. AB - According to our opinion, so-called venous leakage is not a venous disease but a result of impaired cavernous tissue. Since in over 90% of all patients with venous leakage arterial disease has also been discovered, and since in addition ultrastructural degenerative processes have also been detected in the cavernous bodies, we consider the traditional treatment in the form of venous surgery unphysiological and illogical. We suggests arterial revascularization combined with mechanical penis banding as a new therapeutic concept. PMID- 1926677 TI - [Pheochromocytoma of the urinary bladder. Diagnosis and therapy based on a case report]. AB - Micturition difficulties associated with unstable hypertension, tachycardia and profuse sweating could be a sign of pheochromocytoma of the urinary bladder. Of all pheochromocytomas, 10-36% are located extradrenally, in which case they are also referred to as paragangliomas, and 1-3% are found in the urinary bladder. The case history of a 44-year-old female patient with typical symptoms is described. Diagnosis required not only CT, NMR, excretory urography and MIBG scintigraphy, but also hormonal analyses. Histology reveals malignancy in up to 20%; it is thought that focal invasions of tumor into vessels and destruction of connective tissue might be pathognomonic. A precise history and careful diagnosis are necessary before a pheochromocytoma of the bladder can be disclosed and treated. PMID- 1926678 TI - [Methemoglobinemia in calves with emphasis on the dam-calf relationship and after experimental administration of nitrates]. AB - A field investigation of methaemoglobinaemia was performed in healthy calves and in calves suffering from diarrhoeas at different age periods; methaemoglobinaemia of dairy cows and their newborn calves was examined at the average age of 2.5 days. In the other part of this study, NO-3-ion was administered experimentally per os to the calf organisms at doses of 0.15 and 0.3 g KNO3.kg-1 liveweight; this treatment induced a low to medium degree of clinical methaemoglobinaemia. The results of this study indicate that it is possible to comment on the physiological standard of methaemoglobinaemia (less than 3% MaHb) in the total haemoglobin, urgent time of methaemoglobin detection after nitrate intake (2 to 8 h) with respect to the fast dynamics of nitrates, and the importance of subclinical form of methaemoglobinaemia and its relationship to the ontogenetic development of piglets. PMID- 1926679 TI - [Enzymatic activity in the placenta in cows in relation to the course of parturition]. AB - The activity of aminopeptidases and cathepsins was determined in placentoma homogenates; placentomas of cows were extirpated immediately after parturition and in four and eight hours. In cows with afterbirth retention (a. r.) following induced parturition, the activity of these enzymes was always higher than in cows without a. r., no matter if after induced and spontaneous parturitions; it was at a similar or slightly higher level than in the eighth month of pregnancy. The content of total proteins in placentomas of cows with a. r. was also higher. These findings point to the insufficient ripening, or aging of placental tissue, which is related to a release of lysosomal enzymes. The enzymes are active through hydrolysis in the separation of foetal placenta from the maternal one and in the modification of proteins participating in intercellular linkages. PMID- 1926680 TI - [The effect of monensin on the fermentation of feed with different proportions of hay and concentrate in an artificial rumen (rumen simulation technic)]. AB - An experiment was conducted with rumen pouch (RUSITEC--Rumen Simulation Technique). In four fermentation vessels (V), percent proportions of hay and barley were as follows: V1--40:60, V2 - 60:40, V3--80:20 and V4--100:0. Every day 5 mg of monensin dissolved in 1 ml 96% ethanol were added to each fermentation vessel. All diets were isonitrogenous, and after an addition of urea the crude protein (CP) content made 13% in each diet. The experiment lasted 12 days: so called steady state period took the first six days when the fermentation conditions were stabilized. Monensin reduced dry matter digestibility, production of total volatile fatty acids, acetic acid, n-butyric and isovaleric acids and acetate: propionate proportion, and it increased the production of propionic and n-valeric acids. The production of methane and CO2 decreased. The higher proportion of hay in diets decreased dry matter digestibility, digestibility of detergent fibre, total and individual volatile fatty acids, CO2, methane energy yield of volatile fatty acids (E), glucose utilization, production of adenosine triphosphate and production of fermented hexoses. The production, utilization and recovery of metabolic hydrogen also decreased. The effectiveness of microbial matter synthesis (YATP = 11.3) was highest during the fermentation of feed containing 60% hay and 40% barley. PMID- 1926681 TI - [Lysosomal activity in enterocytes in the small intestine in piglets experimentally infected with Isospora suis]. AB - The lysosomal activity of enterocytes of the small intestine mucosa was investigated in gnotobiotic and conventional piglets experimentally infected on the first day after birth (DAB) by the oocysts of the coccidia Isospora suis. A method of the proof of beta-D-glucuronidase (EC.3.2.1.31.) activity was used to demonstrate lysosomes. The piglets were infected by different infection doses of oocysts (100,000 oocysts in gnotobiotic piglets and 200,000 oocysts in conventional piglets). In the gnotobiotic infected piglets the activity of beta-D glucuronidase in enterocyte lysosomes was investigated in the period from day 3 to day 11 after infection (DAI) and in the infected conventional piglets in the period from day 2 to day 10 after infection. Comparing the control piglets, the group of gnotobiotic piglets at the age of 2-5 days and the group of conventional piglets at the age of 4-7 days, the higher activity of beta-D-glucuronidase was demonstrated in the lysosomes of intestinal mucosa enterocytes in the gnotobiotic control piglets (+5.30 of the average density value, Dx). In the infected gnotobiotic and conventional piglets the pattern of beta-D-glucuronidase activity was found to have three stages in the course of this infection. Two stages can be characterized by a great increase in the enzyme activity (DAI 3-9 in gnotobiotic piglets, DAI 2-3 and 7-9 in conventional piglets. The third stage, which is manifest mainly in the conventional infected piglets, is characterized by a marked decrease in the activity of beta-D-glucuronidase, reaching the level of control findings (DAI 10 and mainly 11 in gnotobiotic piglets. DAI 4-6 and 10 in conventional piglets). A topographical picture shows that the two stages of increase and the stage of beta-D-glucuronidase activity decrease occur in the whole small intestine without any predisposition defect of the enzyme in the different sections of the small intestine. PMID- 1926682 TI - [Verification of the method of testing the efficacy of anti-fasciola agents on the juvenile stage of Fasciola hepatica in laboratory mice]. PMID- 1926683 TI - [Botulism in birds living in an aquatic environment in Nove Mlyny in the Breclav District]. AB - Epizootic of wild water birds caused by the toxin Clostridium botulinum of C type occurred in extensive shallow artificial lakes of the Nove Mlyny dam system from May to October 1988 and later on from February to early April 1989. In total more than 3,000 dead or dying birds of 44 species were found, the following orders were prevailing: Anseriformes (56%), Lariformes (33%), Charadriiformes (6%) and Ralliformes (4%). Botulotoxin was detected at high concentrations in sarcophagic fly larvae of Calliphora vomitoria and Lucilia sericata which were collected in bird cadavers, but it was not found in different components of the aquatic environment (water, submersed vegetation, phytoplankton, zooplankton, Gastropoda, Crustacea, Oligochaeta, larvae of Odonata, Chironomidae and Ceratopogonidae). Future development of the epizootic situation in the Nove Mlyny artificial lakes will depend on the water level and meterological conditions in the critical period (May to September). PMID- 1926684 TI - [Occurrence of staphylococcal species in clinically healthy domestic animals]. AB - The incidence of staphylococcus species in healthy animals was investigated in young and adult individuals of cattle, in pigs and in domestic fowl, using the method of selective isolation of strains. A total of 6066 samples was examined; 4567 strains were revealed and they included all known species, except Staphylococcus caseolyticus, S. saccharolyticus, S. schleiferi and S. lugdunensis. 3.8% of strains failed to be identified with any species. The test samples were taken from slaughtered animals, only in calves intravital smears of tonsils were examined. The species most frequently isolated from the tonsil tissue in adult cattle were as follows: S. aureus (19.9%), S. saprophyticus (12.4%), S. hyicus (8.8%) and S. hominis (8.6%). The following species were isolated from the lung tissue: S. saprophyticus (28.8%), S. cohnii (10.6%) and S. epidermidis (10.2%); from the mammary gland parenchyma these were the species S. saprophyticus (17.4%), S. xylosus (13.1%) and S. epidermidis (10%). In the tonsil tissue of pigs the percent proportions of S. aureus and S. hyicus were 44.5% and 31.8%, respectively; the most frequent species detected from the lungs were S. aureus (20.6%), S. saprophyticus (12.3%), S. hyicus (12.1%) and S. epidermidis (11.5%). In domestic fowl the most frequently occurring species were S. epidermidis (23.7%), S. gallinarum (16.5%) and S. aureus (15.4%). In calves the incidence of S. xylosus (37%), S. saprophyticus (19.2%) and S. cohnii (15.2%) was found to be highest. The indicence of the other staphylococcus species in all test animals can be expressed by low percentages. PMID- 1926685 TI - Effect of giving enrofloxacin in the diet to pigs experimentally infected with Actinobacillus pleuropneumoniae. AB - Three groups of 16 pigs were exposed individually when four weeks old to intranasal infection with 10(8.9) viable Actinobacillus pleuropneumoniae (serovar 3, strain 2/(10P2); a fourth group was kept in isolation from the others as uninfected controls. Seven days later the 62 surviving animals were killed and necropsied. The organism had caused typical, mainly subacute disease in 12 of the 16 unmedicated animals but in only two of the 16 which had had continuous access to a diet containing 150ppm of enrofloxacin from four hours before exposure to infection, and in six of the 16 given 32 ppm enrofloxacin. However, only 150 ppm enrofloxacin produced marked control of the infection in terms of reduced average severity of thoracic lesions and much reduced prevalence of the organism in the lung at necropsy, and the mean weight gain (1.55 kg) and feed conversion efficiency (2.08) of this infected group over seven days were similar to those of the unmedicated, uninfected controls (1.67 kg and 2.25). The infected but untreated group on average produced detectable antibody seven days after infection whereas in the infected and medicated groups a specific response against serovar 3 was absent. PMID- 1926686 TI - Leucocytozoon-like infection in parakeets, budgerigars and a common buzzard. AB - The gross and histological lesions of a protozoan infection, possibly caused by Leucocytozoon, in parakeets (genera Neophema and Cyanoramphus), budgerigars (Melopsittacus undulatus) and a wild buzzard (Buteo buteo) are described. The infection appears not to have been identified before in budgerigars in Great Britain, and in its chronic form resulted in vomiting and wasting. The possible identity of the parasite and the epidemiological factors are considered. PMID- 1926687 TI - Cardiac failure in beef cattle fed dried poultry litter. PMID- 1926688 TI - Sheep and goat health scheme. PMID- 1926690 TI - Dog identification. PMID- 1926689 TI - Disposal of carcases. PMID- 1926691 TI - Homoeopathic medicines. PMID- 1926692 TI - Medical diets for dogs and cats. PMID- 1926693 TI - Anthelmintic resistant nematodes in goats. PMID- 1926695 TI - Multidisciplinary team looks at the ethics of experimentation. PMID- 1926696 TI - Euro MPs force rethink on food rules. PMID- 1926694 TI - Polymyositis associated with Leptospira australis infection in a dog. PMID- 1926697 TI - Stricter rules on food residues proposed. PMID- 1926699 TI - Clinical and pathological findings in two Mauritian pink pigeons (Columba mayeri). AB - Two Mauritian pink pigeons (Columba mayeri) from a captive breeding programme, with locomotor disorders were examined clinically and post mortem. One bird was unable to fly owing to a permanent luxation of the left elbow. The other bird had an inclined foot caused by a medial curvature and outward rotation of the tarsometatarsal bone, a deformity similar to the previously recorded 'inclined feet' in birds bred in Mauritius. PMID- 1926700 TI - Agenesis of the mesocolon causing colic in a foal. PMID- 1926698 TI - Effects of chronic lameness on the concentrations of cortisol, prolactin and vasopressin in the plasma of sheep. AB - Plasma cortisol, prolactin and vasopressin concentrations were measured by radioimmunoassay in blood samples from control and lame sheep. The lame sheep were all suffering from naturally occurring clinical cases of footrot and showed all the behavioural characteristics of chronic pain; they were scored for impairment of gait and pathology of the foot and divided into mild and severely lame groups. The severely lame sheep had increased plasma prolactin and decreased plasma cortisol concentrations. Plasma vasopressin was variable and showed no consistent changes with lameness. The relationships between plasma cortisol, prolactin and vasopressin may be a useful index in the assessment of animals experiencing chronic pain, when taken in conjunction with other measurements. PMID- 1926701 TI - Congenitally fused labiae vulva in a heifer. PMID- 1926702 TI - Anthelmintic resistance in Scotland. PMID- 1926703 TI - Identification of spayed bitches. PMID- 1926704 TI - Treatment of watery mouth in lambs. PMID- 1926705 TI - Wing tip oedema and dry gangrene in birds. PMID- 1926706 TI - Eradication of East Coast fever. PMID- 1926707 TI - Outbreak of 'tetanus'. PMID- 1926708 TI - Effective mite treatment. PMID- 1926710 TI - Suspected Adverse Reaction Surveillance Scheme (SARSS): 1990 report. PMID- 1926709 TI - Pig disease name. PMID- 1926711 TI - Effects of detomidine on equine oesophageal function as studied by contrast radiography. AB - The effects of sedation with detomidine on oesophageal function were assessed by contrast radiography in 10 healthy adult thoroughbred horses. Barium swallows were monitored by means of image intensification, first without sedation and then after the intravenous administration of detomidine at doses of 10 and 20 micrograms/kg bodyweight. The transit time of contrast agent to the oesophageal hiatus was recorded and each swallow was scored for markers of oesophageal dysfunction. Analysis of the data indicated that there were highly significant dose dependent increases in the transit time, the retention of barium within the longitudinal mucosal folds, and retrograde peristalsis and pooling of contrast agent within the oesophagus at both the thoracic inlet and caudal to the base of the heart. The degree of gastrooesophageal reflux was not affected at either dosage. These changes in oesophageal function were similar to those recorded from cases of grass sickness and indicate that care should be taken in the interpretation of studies of swallowing in animals that have been given detomidine before a radiographic examination. PMID- 1926712 TI - Relationship between kennel size and stress in greyhounds transported short distances by air. AB - Greyhounds are usually transported by air between Ireland and England in wooden kennels similar in size to greyhound racing starting traps. These kennels have been criticised in the belief that their small size leads to unnecessary stress. The present study compared plasma ACTH, cortisol, lactate and non-esterified fatty acid concentrations in 12 greyhounds transported either in the existing wooden kennels or in wider perspex kennels, which were stowed either in the belly hold or in the main cargo hold of jet freighter aircraft. Increased kennel size did not appear to result in decreased stress responses but there was a significantly greater stress response in the dogs kept in the belly hold of the aircraft. Individual variation between dogs was the most significant feature of the study. PMID- 1926713 TI - Disposal of carcases. PMID- 1926714 TI - Outbreak of tetanus. PMID- 1926715 TI - Tendon splitting and other treatments. PMID- 1926716 TI - Laboratory blood tests. PMID- 1926717 TI - Pigeon conditions. PMID- 1926719 TI - Neutering dangerous dogs. PMID- 1926718 TI - Treatment of adder bites. PMID- 1926720 TI - 'Porcine reproductive and respiratory syndrome' in Quebec. PMID- 1926721 TI - Zoo welfare rules. PMID- 1926722 TI - Yersinia pseudotuberculosis in a persian cat. PMID- 1926723 TI - Outbreaks of 'tetanus'. PMID- 1926724 TI - Studies on the incidence of clinical mastitis and blood levels of vitamin E and selenium in dairy herds in England. AB - In a trial conducted in the south of England in January to February 1989, blood samples were obtained from nine dairy herds with more than 30 cases of clinical mastitis/100 cows and from nine herds with less than 30 cases/100 cows during the previous 12 months. Whole blood glutathione peroxidase (GSHPx) activity and plasma vitamin E concentration were determined for 12 cows in each herd. The mean (+/-sd) values for the herds with the lower incidence of mastitis were 7.57 +/- 1.86 micrograms/ml plasma vitamin E and 23.8 +/- 22.8 U/ml rbc GSHPx activity, compared with 7.74 +/- 1.69 micrograms/ml plasma vitamin E and 20.61 +/- 8.8 U/ml rbc GSHPx activity for the herds with the higher incidence of the disease. These values indicate that the vitamin E levels were generally adequate but that some animals and herds had low GSHPx activities, suggesting that their diets may have contained inadequate selenium. The activities of GSHPx and the vitamin E levels in plasma were not significantly different in the two groups of herds, and no relationship was found between the two nutrients and the incidence of clinical mastitis. However, there was a significant negative correlation between the activity of GSHPx and the bulk milk cell counts in the herds with a low incidence of mastitis suggesting that there was an association between the incidence of subclinical mastitis or inflammation and the selenium status of these herds. PMID- 1926725 TI - Vaccination of sheep with a live incomplete strain (S48) of Toxoplasma gondii and their immunity to challenge when pregnant. AB - Sixty-four ewes were vaccinated with tachyzoites of an incomplete strain (S48) of Toxoplasma gondii grown either in the peritoneal cavity of mice (group 1) or vero cell culture (group 2) and 30 ewes (group 3) were not vaccinated. All the ewes were mated 77 days later and challenged orally with 2000 sporulated oocysts at 89 to 90 days of gestation. Ten additional unvaccinated (group 4) and 10 vaccinated (group 5) control ewes were not challenged. The unvaccinated ewes developed a characteristic febrile response to challenge while in the vaccinated ewes the fever commenced earlier but was less severe and of shorter duration. After challenge, the antibody titres against T gondii rose rapidly to high values in the vaccinated ewes while the ewes in group 3 responded more slowly. Only eight of the 45 fetuses/lambs (17.8 per cent) from group 3 were viable compared with 72.3 per cent of those in group 1 and 80.8 per cent of those in group 2. Gestation in the unvaccinated challenged ewes was shortened and the mean birthweight of their single, viable offspring was significantly lower than the weight of single lambs from the vaccinated (groups 1 and 2) and control ewes (groups 4 and 5). Examination of precolostral sera showed that almost two-thirds of the lambs from the vaccinated ewes were infected in utero. The 20 control ewes appeared clinically normal at all times and lambed normally. The two vaccine preparations were equally effective. PMID- 1926726 TI - Two horses with hypocalcaemia. PMID- 1926727 TI - Stillbirth and perinatal weak calf syndrome. PMID- 1926728 TI - Long-acting antibiotic formulations in the treatment of calf pneumonia: a comparative study of tilmicosin and oxytetracycline. AB - The treatment of an outbreak of acute pneumonia in 50 four- to eight-month-old Friesian and Friesian cross calves is described. At the first visit (day 0) 16 calves received 20 mg/kg bodyweight of oxytetracycline dihydrate intramuscularly and 15 received 10 mg/kg of the macrolide tilmicosin subcutaneously. The remaining 19 in-contact animals were not considered ill enough to be included in the trial and received 20 mg/kg of oxytetracycline dihydrate. The rectal temperature, demeanour, respiratory rate and respiratory effort of each calf was assessed on days 1, 2, 3, 9, 14, 21 and 28, and calves which had not responded were given repeat injections of the same antibiotic. All the calves recovered from the outbreak and of the 19 calves treated strategically, three required a second injection. Among the calves with clinical pneumonia, fewer treatments (P less than 0.01) were required by those treated with tilmicosin. The rectal temperatures of both groups decreased (P less than 0.05) after the first injection, but on day 3 the decrease was greater (P less than 0.05) in the group treated with tilmicosin. Respiratory rates varied widely but respiratory effort was less (P less than 0.05) on day 2 in the calves treated with tilmicosin. When long-acting antibiotic injections are used to treat enzootic pneumonia it is suggested that a second visit should be made on day 3 to assess the animals' response to treatment. PMID- 1926729 TI - Medical treatment of right-sided dilatation of the abomasum in cows. AB - Twenty-two cows with right-sided displacement of the abomasum were treated with hyoscine-n-butyl bromide and dipyrone (Buscopan compositum; Boehringer Ingelheim). Within 24 hours 11 had recovered completely, three had improved, six had shown no improvement and two had been slaughtered. Within 48 hours 17 of the cows had recovered completely and five had been slaughtered. PMID- 1926730 TI - Citrinin as a possible cause of the pruritus, pyrexia, haemorrhagic syndrome in cattle. AB - An outbreak of the pruritus, pyrexia, haemorrhagic syndrome affected eight of a herd of 175 cows which was divided into two groups of 115 and 60 according to yield. There was no difference in management between them but citrus pulp pellets were fed only to the larger group in which the eight cows were affected. Silage, which had been made without the use of additives, was also fed to both groups. The citrus pulp was visibly mouldy and contained 30 to 40 parts per billion of citrinin. Signs of the syndrome occurred within three days of the cows starting to ingest the citrus pulp, which was fed for 21 days, and the last case occurred six days after the feeding of citrus pulp ceased. Five calves whose dams had been fed citrus pulp were subsequently born with superior prognathism. In contrast to the eight cows that developed the syndrome only one out of 68 heifers which were fed larger quantities of citrus pulp for 10 days developed mild signs of the syndrome and then recovered, suggesting that older animals may be more susceptible. The clinical signs, gross pathology and histopathology are described and compared with those of previous outbreaks. Mycotoxins, particularly citrinin, were strongly implicated as the cause of this outbreak. PMID- 1926731 TI - A survey of dairy farmers' decisions concerning the control of leptospirosis. PMID- 1926732 TI - A policy for a unified meat service. AB - Unification of meat hygiene control in Britain would lead to an improved service in terms of hygiene and welfare and would ensure continuity from the Minister through to the abattoir meat hygiene team. This in turn would increase consumer confidence in British meat both at home and abroad, and would enable compliance with EC meat hygiene requirements for harmonisation beyond 1992. The level of veterinary supervision and control required throughout the meat plant process has not yet been fully determined by the EC. However, the BVA envisages a team approach headed by a veterinarian with the level of direct veterinary involvement tapering from farm to table. BVA envisages an agency operating along the lines of the current Veterinary Medicines Directorate, with a similar identity but relating to meat hygiene and the welfare of animals at slaughter. Such a unified system could operate more efficiently and more economically than smaller separate organisations. Such a system would ensure even application of standards, avoid duplication of activities, and save money by efficient use of staff and resources. The structure would also allow for better salaries and career prospects than smaller local authority units can provide. This would lead to recruitment and commitment of more highly qualified staff. The purpose of the reorganisation would be to establish a meat quality control service which would ensure that meat and meat products supplied to retail outlets are hygienically produced to standards set down by the EC. Such a service would replace the variable standards of local authority departments and enable MAFF to discharge its EC responsibility as the 'competent authority'.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1926733 TI - The role of the veterinarian in fish farming and aquaculture. PMID- 1926734 TI - Problems with Vietnamese pot-bellied pigs. PMID- 1926735 TI - Salmonella in terrapins. PMID- 1926736 TI - Worming bitches. PMID- 1926737 TI - Detection of Toxoplasma gondii in equine eyes. PMID- 1926738 TI - Treatment of entropion in lambs. PMID- 1926739 TI - Aquaculture drug development: a pharmaceutical industry perspective. PMID- 1926740 TI - Major infectious and parasitic diseases of channel catfish. PMID- 1926741 TI - Overview of diseases and drug needs for major aquaculture species: shrimp. PMID- 1926742 TI - IR-4/FDA Workshop for Minor Use Drugs: Focus on Aquaculture. Opening remarks. AB - Aquaculture has become a highly technical industry. There is a great need for the producers, scientists, government agencies, and drug manufacturers to become more involved in the drug development process so that the industry continues its growth. I believe that this should be the major goal of this conference. I urge all of the attendees to participate intensely in our round tables to make this goal a reality in future years. PMID- 1926743 TI - Overview of selected diseases and drug needs for salmonids. PMID- 1926744 TI - Potential uses and limitations of chemotherapeutics in control of major diseases of cultured shellfish in North America. PMID- 1926745 TI - Major diseases of striped bass and redfish. AB - Diseases of striped bass, their hybrids, and redfish (red drum) are important constraints to the culture of these two species. Since striped bass have been cultured for years the organisms that cause most diseases of these fish are well known, but very little specific disease information exists for redfish. However, it appears that the organisms that cause diseases of striped bass and redfish do not differ greatly from those of other fishes. The most significant viral disease is lymphocystis, but infectious pancreatic necrosis has occurred in striped bass. Vibriosis (Vibrio sp.) and motile Aeromonas septicemia (Aeromonas hydrophila) are the most frequently encountered bacterial diseases. Both species of fish are affected by fungi (usually Saprolegnia) when the fish are injured or stressed. Amyloodinium ocellatum is the most serious protozoan that infects striped bass and redfish, but the other common protozoans (Trichodina, Ichthyophthirius, Cryptocaron, etc.) have also been reported. Treatment of any of these diseases is a problem because of the absence of approved drugs or chemicals for use on striped bass or redfish. The most common therapeutics used on striped bass and redfish are copper sulfate, formalin, salt (in freshwater) and Terramycin. PMID- 1926746 TI - An overview of current programs on drug development and regulation for aquaculture: US Fish and Wildlife Service perspective. PMID- 1926747 TI - The veterinary practitioner's role in aquaculture. PMID- 1926748 TI - Enrofloxacin in salmonids. PMID- 1926749 TI - Oral and injectable applications of erythromycin in salmonid fish culture. AB - Erythromycin is a macrolide antibiotic effective against Renibacterium salmoninarum, causative agent of bacterial kidney disease in salmonids. Although erythromycin is used on an experimental basis in private and conservation hatcheries, the drug is not registered with the US Food and Drug Administration for use in fish culture. Residues of erythromycin are retained in the tissues of juvenile and adult salmon for some time following administration of oral or injectable forms of the drug, a characteristic that may be important in the drug's efficacy against the slow growing R. salmoninarum pathogen. Before erythromycin can be registered, additional information must be collected about efficacy, toxicity, and environmental consequences of administration. PMID- 1926750 TI - Regulatory and scientific roles for biodistribution studies in aquatic species. AB - The advantage of focusing on biliary excretion of drugs and other xenobiotics is emphasized in this discussion of the regulatory and scientific roles for biodistribution studies in aquatic species. The role of the hepatobiliary system in the overall disposition of absorbed chemicals is briefly reviewed. The present survey includes 18 drugs, 6 petroleum hydrocarbons, and 16 different fish species. The fact that aquatic species concentrate most xenobiotics and their metabolites into bile to as much as several orders of magnitude underscores the advantage of using bile rather than tissue to determine whether aquatic species are being exposed to given chemicals. Until these advantages are recognized, analysis of edible muscle tissue remains the method of choice for assessment of human exposure to chemicals. PMID- 1926751 TI - An overview of current programs on drug development and regulation for aquaculture: Regional Aquaculture Center perspective. PMID- 1926752 TI - Current issues affecting aquaculture drug clearances. PMID- 1926753 TI - Focus on metabolism studies and data requirements for aquaculture species. PMID- 1926754 TI - US Department of Agriculture perspective. PMID- 1926755 TI - Compliance issues and proper animal drug use in aquaculture. PMID- 1926756 TI - The changing autopsy. PMID- 1926757 TI - DNA cytophotometry in adrenocortical tumours: a clinicomorphological study of 66 cases. AB - Surgical specimens of 66 adrenocortical tumours were investigated by conventional microscopy and DNA cytophotometry. Histologically, 50 neoplasms were classified as adenomas and 16 as carcinomas. In only 8 of the latter cases were distant metastases and/or a lethal outcome recorded. On single cell scanning cytophotometry either non-euploid or aneuploid DNA histograms were identified in 24 of 50 adenomas (48%) and in 14 of 16 carcinomas (88%). The two carcinomas exhibiting euploid DNA distributions fell into the group of 7 malignancies which are recurrence-free so far. From these findings it is concluded that DNA measurements have no diagnostic and only limited prognostic value in neoplasms of the adrenal cortex. PMID- 1926758 TI - Immunohistochemical distribution patterns of epidermal growth factor receptor in malignant mesothelioma and non-neoplastic mesothelium. AB - An immunohistochemical study of the epidermal growth factor (EGF) receptor in non neoplastic pleural mesothelium (35 cases) and in human malignant mesothelioma (36 cases) was made, using a murine monoclonal antibody OM-11-951. All malignant mesotheliomas and non-neoplastic pleural biopsies exhibited a strong cytoplasmic immunoreactivity in mesothelial cells. Nuclear immunoreactivity was detected in mesothelial cells of all specimens of both malignant and non-neoplastic pleura. No statistically significant differences were found between malignant mesothelioma and non-neoplastic pleural mesothelium. There were differences, between the three subtypes of mesothelioma, in the number of cells that exhibited nuclear staining. Statistically significant differences were noted between the epithelial subtype and the mesenchymal subtype (P less than 0.005), epithelial subtype versus the mixed cell type (P less than 0.005) and between the mesenchymal component of the mixed cell type and the mesenchymal type (p less than 0.0005). We conclude that there is strong expression of EGF receptor in both malignant mesothelioma and in non-neoplastic pleural mesothelium. Different staining patterns are seen when comparing the different subtypes of mesotheliomas with each other. EGF receptor expression cannot be used to distinguish between malignant and benign mesothelium. PMID- 1926759 TI - Metastatic and invasive tumours involving the heart in a geriatric population: a necropsy study. AB - In a series of 744 necropsied subjects with a diffuse malignant process, 57 cases of cardiac involvement were observed (50 metastatic carcinomas and 7 lymphomas or myeloproliferative disorders). The most frequent site of involvement was the pericardium and epicardium in lung or breast carcinoma, suggesting regional lymphatic invasion. Myocardial involvement was rarer and usually associated with cutaneous melanoma and lymphoma, suggesting haematogenic invasion. Endocardial involvement was exceptional. The multiple causes of heart disturbance in the elderly cloud the clinical diagnosis of such cardiac involvement; however, isolated pericardial and/or epicardial abnormalities should heighten suspicion of a neoplastic process. PMID- 1926760 TI - Candidiasis visualised by proteinase-directed immunofluorescence. AB - The secretory aspartic proteinases of Candida albicans and C. tropicalis are potential factors for virulence produced during infection. By indirect immunofluorescence, we have demonstrated proteinase antigen on elements of both species in deparaffinized tissue sections derived from clinical cases of mucosal and deep-seated candidiasis. Occasionally, we observed a halo of fluorescence in the close vicinity of candidal cells, which may reflect secretion of the enzyme. In kidneys, a ring of amorphous fluorescent material surrounding candidal colonies may illustrate alkaline denaturation of secreted enzyme within a pH gradient, which is generated by the fungus. Our findings support the view that candidal proteinase may be a diagnostically relevant antigen. PMID- 1926761 TI - Osteoporosis in longstanding acromegaly: characteristic changes of vertebral trabecular architecture and bone matrix composition. AB - Although it is now 60 years after Erdheim's (1931) detailed description of vertebral alterations in severe acromegaly, it is still unclear whether osteoporosis is a consistent feature of acromegalic bone disease or not. We studied the vertebral trabecular bone of a 44-year-old woman who had suffered active acromegaly for more than 20 years, and compared it with 17 normal as well as 2 osteoporotic controls. Histomorphometry revealed a very low trabecular bone volume and thus documented the presence of osteoporosis. The mean trabecular plate thickness was strikingly increased in acromegaly (possibly caused in part by a low-dose fluoride treatment), whereas it was normal or reduced in the osteoporotic controls. The meticulous analysis showed islands of cartilaginous tissue in the core of the acromegalic trabeculae which were not present in any other sample. In these areas collagen II was detected by immunohistochemistry. Biochemical analysis revealed that collagen II accounted for 7% of the total collagenous matrix. The degree of hydroxylation of lysyl residues of collagen I was close to the average value of all control samples studied. Our data show that osteoporosis can occur in acromegaly and that it is characterized by unusual architectural and compositional features. These findings challenge the prevailing view that the matrix of osteoporotic bone always shows a normal composition. PMID- 1926762 TI - Neoglycoprotein binding to colorectal tumour cells: comparison between primary and secondary lesions. AB - Biotinylated neoglycoproteins are useful to determine the expression of sugar receptors (lectins) histochemically in routinely processed tissue sections. Assessment of the presence of distinct receptor classes with specificity to beta galactosides and to alpha- or beta-N-acetylgalactosamine, selected on the basis of their potential relevance for recognition processes within the metastatic cascade in murine model systems, was performed for a common human tumour type, colorectal cancer. The four different types of neoglycoproteins, derived from covalent attachment of commercially available derivatives of beta-N acetylgalactosamine, differed only quantitatively in their capacity to detect specific binding on cultured cells and tissue sections, thus posing no major restriction on the choice of synthetic process for histochemical efficiency of the product. Glycocytological application revealed specific probe binding and a regulation of level of receptor expression for a human colon carcinoma cell line primarily for N-acetylgalactosamine-specific receptors upon retinoic acid-induced differentiation. Monitoring of sections of the 12 cases of primary and secondary colorectal lesions invariably disclosed the presence of the respective receptors, the extent of cell labelling in primary tumours and metastases being similar. Establishment of metastases, even in different target organs, is apparently not followed by a major phenotypic variation in this feature. PMID- 1926763 TI - Effect of alpha-difluoromethylornithine on the polyamine levels and proliferation in two transplantable tumours. AB - The effect of inhibition of polyamine biosynthesis by alpha difluoromethylornithine (DFMO) on the growth of two murine transplantable tumours was studied. Female CBA mice were implanted with either the sarcoma F (SaF) or an anaplastic mammary carcinoma (CaNT), and 3% DFMO in the drinking water was provided once the tumours were established. Over a 10-day period control SaF tumours increased exponentially from 20 mm3 to over 800 mm3, whereas DFMO-treated SaF reached only 300 mm3. CaNT grew more slowly, requiring 22 days to achieve a similar volume increase, and DFMO was as effective in retarding growth as it had been in SaF. DFMO depleted tumour tissues of putrescine and spermidine, but did not reduce spermine levels. Metaphase arrest experiments with vincristine demonstrated that DFMO could substantially reduce the rates of tumour cell production, but there was no indication the DFMO accelerated the rate of cell loss from the tumours. Despite reduced rates of cell production, labelling studies with bromodeoxyuridine failed to detect differences between control and treated tumours: an increase in transit time through the S-phase was suspected. The number of nuclear organizer regions, detected by the argyrophilia of their associated proteins, was less in DFMO-treated tumours, and within a tumour the degree of silver deposition unequivocally reflected the proliferative heterogeneity. Ultrastructural studies revealed no differences between DFMO treated and untreated tumours. PMID- 1926764 TI - Morphometric investigations on intrarenal vessels of streptozotocin-diabetic rats. AB - We have investigated 975 different grazing sections of vessels in kidney preparations of 20 rats of the Wistar strain. Half of these genetically identical animals had an insulin-deficiency diabetes induced by injection of streptozocin. The kidneys were removed for investigation after 2 and 12 weeks duration of diabetes. The vessel cross-section, wall, lumen and endothelial surface area were determined in renal arteries, arterioles and preglomerular afferent arterioles in a blind experiment. Statistically detecteable changes were found in the diabetic vessels in the early stage of the diabetes. Preglomerular afferent arterioles showed a highly significant and increasing lumen dilatation commencing after 2 weeks. Diabetic arteries and arterioles developed narrower lumina. A significant thickening of the endothelium took place at the same time in both vessel types. All three vessel regions became smaller and had thinner walls than healthy vessels as the diabetes progressed. The findings on the afferent vessels indicate that haemodynamic effects on the glomerulus are to be expected. Familial diabetic gloermulopathy begins with a reversible hyperfiltration. However, the mechanism has not been clarified in the context of the diabetic metabolic disorder, and this change is probably the haemodynamic consequence of the substantial dilatation of the preglomerular afferent arterioles. With their renin-positive segment, these arterioles are the centre of intrarenal regulation. The increase of the capillary glomerular pressure associated with the dilatation of the preglomerular afferent arterioles is a crucial factor in the development of diabetic glomerulopathy. PMID- 1926765 TI - Immunoelectron microscopy shows an atypical pattern and a quantitative shift of collagens type I, III and VI in oral Kaposi's sarcoma of AIDS. AB - The localization of collagen types I, III and VI in normal human alveolar and palatal mucosa and in oral Kaposi's sarcoma (KS) was studied by light microscopy and cryo-immunoelectron microscopy. Normal oral mucosa revealed two different types of organization. The upper connective tissue stroma contained a loose reticular network mainly composed of collagen types III and VI, while collagen type I immunostaining predominated in the deeper stroma. Ultrastructurally, in the KS tumour stroma, a loose pattern of individual thin collagen fibrils was noted. These often fanned out at their ends showing a filamentous substructure. The fibrils consisted predominantly of collagen type I similar to individual fibrils of normal oral mucosa. However, there was a marked loss of thick fibre bundles of collagen types I and III in KS compared with normal oral mucosa, whereas collagen type VI was markedly increased and found preferentially in clusters and strands around cross-striated fibrils that often spanned the distance between single collagen fibres. The abundance of collagen type VI in a pattern similar to early stages of wound healing suggests that the KS stroma resembles an early organizational stage of the interstitial and vascular extracellular matrix subject to a high rate of collagen turnover. This character of the KS stroma appears to result from a continuous auto-and paracrine stimulation of cell growth and collagen synthesis and provides an excellent model to study the structural arrangement of collagen type VI in relation to the fibrillar collagen types I and III. PMID- 1926766 TI - Do measles early giant cells result from fusion of non-infected cells? An immunohistochemical and in situ hybridization study in a case of morbillous appendicitis. AB - A case of acute appendicitis with features of measles inflammatory reaction is studied. Two types of lymphoid polykaryons are seen: Warthin Finkeldey cells inside germinal centres (LN1 ++, LN2 +, L26 +, MB1 +, MB2 +/-) and multinucleate plasma cells in the lamina propria (mu +, alpha ++, kappa +, lambda +). Both types of polykaryon are devoid of inclusions. The search for viral genetic information by in situ hybridization was negative in these cells. A positive signal was observed in interfollicular mononuclear cells and rare enterocytes. A possible mechanism of fusion from without, acting at the beginning of the disease to induce the appearance of polykaryons, is discussed. PMID- 1926767 TI - Sinus histiocytosis with massive lymphadenopathy (Rosai Dorfman disease) in an HIV-positive patient. AB - We report a case of a 31-year-old HIV infected black female, who presented with asymptomatic generalized lymphadenopathy. Three particularly enlarged lymph nodes were biopsied (2 cervical and 1 axillary). The histological picture was consistent with a diagnosis of sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease. Large histiocytes, positive for a variety of macrophage markers and for the S-100 protein, were observed in the distended sinuses. A few hyperplastic follicles, such as usually seen in HIV-infection associated lymphadenopathy, were present at the periphery of one lymph node. No infections agent besides HIV could be detected by histological or microbiological analysis or by in situ hybridization. This is the first reported case of SHML associated with HIV infection. The possible relationship between the two diseases is discussed. PMID- 1926768 TI - DNA ploidy and cell-cycle analysis in pancreatic and ampullary carcinoma: flow cytometric study of formalin-fixed paraffin-embedded tissue. PMID- 1926769 TI - HIV-associated nephropathy in transgenic mice expressing HIV-1 genes. AB - Transgenic mice were produced that bore copies of a defective HIV provirus. The transgenic offspring from three independently derived mouse lines manifested renal disease associated with proteinuria, a high mortality rate, and HIV specific gene expression in the kidney. An early histopathological lesion in the kidney was focal glomerulosclerosis. Moribund animals had diffuse glomerulosclerosis with prominent microcystic tubular dilatation, tubular epithelial degeneration, and interstitial nephritis. Electron microscopy revealed ultrastructural features consistent with the glomerulosclerosis: effacement of the foot processes of visceral epithelium and an increase in mesangial cell matrix. Transgenic mice variably expressed 6-, 4.3-, and 2-kb HIV-specific RNAs and HIV-related polypeptides in several tissues including kidney. Immunocytostaining revealed the presence of HIV-related protein in the glomeruli of affected animals. Glomerulopathy in these transgenic mice and HIV-associated nephropathy in man have similar features. PMID- 1926770 TI - Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. AB - We have recently described the cloning of a portion of the hepatitis E virus (HEV) and confirmed its etiologic association with enterically transmitted (waterborne, epidemic) non-A, non-B hepatitis. The virus consists of a single stranded, positive-sense RNA genome of approximately 7.5 kb, with a polyadenylated 3' end. We now report on the cloning and nucleotide sequencing of an overlapping, contiguous set of cDNA clones representing the entire genome of the HEV Burma strain [HEV(B)]. The largest open reading frame extends approximately 5 kb from the 5' end and contains the RNA-directed RNA polymerase and nucleoside triphosphate binding motifs. The second major open reading frame (ORF2) begins 37 bp downstream of the first and extends approximately 2 kb to the termination codon present 65 bp from the 3' terminal stretch of poly(A) residues. ORF2 contains a consensus signal peptide sequence at its amino terminus and a capsid-like region with a high content of basic amino acids similar to that seen with other virus capsid proteins. A third open reading frame partially overlaps the first and second and encompasses only 369 bp. In addition to the 7.5-kb full length genomic transcript, two subgenomic polyadenylated messages of approximately 3.7 and 2.0 kb were detected in infected liver using a probe from the 3' third of the genome. The genomic organization of the virus is consistent with the 5' end encoding nonstructural and the 3' end encoding the viral structural gene(s). The expression strategy of the virus involves the use of three different open reading frames and at least three different transcripts. HEV was previously determined to be a nonenveloped particle with a diameter of 27-34 nm. These findings on the genetic organization and expression strategy of HEV suggest that it is the prototype human pathogen for a new class of RNA virus or perhaps a separate genus within the Caliciviridae family. PMID- 1926771 TI - Tomato yellow leaf curl virus: a whitefly-transmitted geminivirus with a single genomic component. AB - The genome of the tomato yellow leaf curl virus (TYLCV), a Bemisia tabaci transmitted geminivirus, was cloned. All clones obtained were of one genomic molecule, analogous to DNA A of African cassava mosaic virus. Nucleotide sequence analysis of the TYLCV genome showed that it comprises 2787 nucleotides, encoding six open reading frames, two on the virion strand and four on the complementary strand. All of them have counterparts in other geminiviruses. Dimeric copies of the cloned viral genome were introduced into tomato plants by agroinoculation. Severe yellow leaf curl disease symptoms developed in all of them. Effective whitefly-mediated transmission of the virus from agroinoculated plants to test plants demonstrated that the cloned molecule carries all the information needed for virus replication, systemic infection, and transfer by whiteflies. Restriction and hybridization analyses of viral DNA forms in infected plants and viruliferous whiteflies did not support the presupposed existence of a second genomic component. This is the first report of a whitefly-transmitted geminivirus that possesses a single genomic molecule. PMID- 1926772 TI - Isolate-specific neutralizing antibodies in patients with progressive HIV-1 related disease. AB - Four individuals with increasing severity of HIV-1 infection were studied for serum neutralizing activity against their own virus isolates collected during 1-3 years. Sequential serum samples and HIV-1 isolates were available from these patients from the stage of lymphadenopathy to severe immunodeficiency. The replicative capacity of isolates changed from slow/low to rapid/high in each patient during the study period. Sequential virus isolates showed differences in sensitivity to neutralization by autologous as well heterologous area. Taken together with our previous results demonstrating that variant viruses resistant to neutralization by autologous sera emerge during the year following primary infection, neutralization-resistant variants seem to emerge during the entire course of HIV-1 infection. The ability to produce neutralizing antibodies to autologous virus appears to correlate with replicative capacity of the virus and the degree of immunodeficiency in the patient. PMID- 1926773 TI - Effects of random mutagenesis upon potato spindle tuber viroid replication and symptom expression. AB - A combination of random chemical mutagenesis plus temperature gradient gel electrophoresis was used to isolate a collection of 57 potato spindle tuber viroid (PSTV) cDNAs containing mutations distributed throughout the entire 359 nucleotide genome. Although the presence of multiple mutations was often associated with a loss of cDNA infectivity, infectious PSTV cDNAs containing as many as four unlinked alterations could be isolated. Several mutations in the pathogenicity domain and left terminal loop were stably maintained in the resulting progeny, but those which affect base pairing in secondary hairpins I and II were either lethal or rapidly reverted to wild-type. One stable C----U substitution which may promote significant structural rearrangement within the right side of the pathogenicity domain had no detectable effect upon symptom expression. The variable domains of several noninfectious mutants contained an A- --G substitution which is likely to inhibit the in vitro formation of secondary hairpin II via stabilization of the native structure, and the lethal nature of this mutation was confirmed by oligonucleotide-directed mutagenesis. Several lines of evidence now point toward an essential role for secondary hairpin II in the replication of PSTV and related viroids. PMID- 1926774 TI - The genetic fate of molecularly cloned simian immunodeficiency virus in experimentally infected macaques. AB - We have examined genetic variation of the simian immunodeficiency virus (SIV) in four macaques inoculated with virions derived from molecular clones of proviral DNA. Our data demonstrated that the SIV genome is capable of rapid and extensive genetic variation. This variation was especially large in the env gene, where nucleotide substitution frequencies were as high as 10(-1)/site/year. In some env clones, a high G to A transition rate was observed that accounted for up to 79% of the observed nucleotide substitutions. Moreover, in env clones with a high G to A transition rate, multiple in-frame stop codons were generated exclusively at tryptophan codons. Another interesting observation was the lack of variation in the region analogous to the V3 loop in the HIV-1 Env protein. Considered together, these data have important implications for studies of pathogenesis and vaccine development in the SIV model system. PMID- 1926775 TI - Nucleotide sequence of the Autographa californica nuclear polyhedrosis 9.4 kbp EcoRI-I and -R (polyhedrin gene) region. AB - The nucleotide sequence of a 9.4-kbp region including the polyhedrin gene of the C6 strain of the Autographa californica nuclear polyhedrosis virus (AcMNPV) genome was determined. These data provide a complete description of the EcoRI-I fragment, which is used to produce transfer vectors for inserting foreign genes into the AcMNPV. Ten potential open reading frames (ORFs) were identified in the complete sequence, on either strand of DNA. The largest of these was 1629 nucleotides in length and was located downstream from the polyhedrin coding sequences, but on the opposite strand of DNA. Northern blot hybridization analysis of ORF 8 (1629) identified an RNA of 2000 nucleotides which was produced in infected cells from 12 hr p.i. and remained until at least 48 hr p.i. S1 nuclease mapping and analysis of cDNA clones located the 3' end of the mRNA at a site 16 nucleotides downstream of the polyhedrin coding sequences. The 5' end of the mRNA was mapped using primer extension analysis of polyadenylated RNA. The mRNA start site was positioned within a late/very late consensus transcription initiation motif (ATAAG), 428 nucleotides upstream from the potential ATG translation initiation codon. The biological significance of the putative gene product was assessed by inserting a synthetic oligonucleotide in the carboxyl terminal coding sequences of ORF 8 (1629) to prematurely terminate translation. Recombinant viruses containing this mutation were not isolated, suggesting that the ORF 1629 gene product is essential for virus replication. PMID- 1926776 TI - Complete nucleotide sequence of the virus SSV1 of the archaebacterium Sulfolobus shibatae. AB - The DNA sequence of the Sulfolobus shibatae virus SSV1 is the first complete sequence of an archaebacterial virus genome. The viral DNA is a closed double stranded DNA circle of 15465 bp. The features of the sequence, the positions of all 11 transcripts, the three characterized proteins, and the open reading frames are described. PMID- 1926778 TI - Identification and nucleotide sequence analysis of an open reading frame involved in high-frequency conversion of turbid to clear plaque mutants of filamentous phage Cf1t. AB - Clear plaque mutants (Cf1c) isolated from the temperate filamentous phage Cf1t occurred at a frequency of approximately 10(-3). The pahge yield from Cf1c infected cells was higher than that from Cf1t-infected cells. Results of spot complementation tests implied that the turbid plaque phenotype is dominant. DNA fragment substitution studies indicated that a NcoI/KpnI fragment of 591 bp was responsible for the determination of plaque turbidity. Sequence data from four Cf1c isolates revealed base pair alterations and a deletion located in the upstream region of an open reading frame (ORFII) which might encode a 18.2-kDa protein. When the ORFII in Cf1t was disrupted by a frameshift mutation, this recombinant phage formed clear plaques. These observations suggest that ORFII may participate in the formation of turbid plaques. ORFII does not show significant homology with the sequence of f1 gpII, gpV, or other known phage proteins. PMID- 1926777 TI - Analysis of alternatively spliced human immunodeficiency virus type-1 mRNA species, one of which encodes a novel tat-env fusion protein. AB - A polymerase chain reaction-based analysis was used to define the structures of the mRNAs that encode human immunodeficiency virus type-1 (HIV-1) regulatory and structural proteins in infected H9 cells. Twenty alternatively spliced mRNAs encoding the vif, vpr, env, nef, tat, and rev proteins were characterized. An evaluation of the coding potentials of these transcripts recognized both leaky scanning and reinitiation at downstream initiation codons as mechanisms that may operate during translation of many of the polycistronic messages. Two new splice acceptor sites, one at nt 6018 defining a new mRNA coding for the env and vpu proteins and another at nt 8671 defining a novel tat-env fusion transcript, were characterized. The latter transcript expressed a novel protein p17tev that was immunoprecipitated by both polyclonal tat antibodies and monoclonals directed towards the C-terminal region of gp41. The p17tev protein was able to transactivate transcription from the HIV-1 LTR in transient transfection assays. The use of multiple alternative splice donor and acceptor sites and the generation of novel proteins may confer evolutionary advantages on the viral mutants encoding them and influence the course of clinical disease. PMID- 1926779 TI - Structure of the glycoprotein gene of sonchus yellow net virus, a plant rhabdovirus. AB - The nucleotide sequence of the glycoprotein (G) gene of sonchus yellow net virus (SYNV), a plant rhabdovirus, was determined from viral genomic and mRNA cDNA clones. The G cistron is 2045 nucleotides (nt) long and the G protein mRNA open reading frame (ORF), as determined from the cDNA sequence, contains 1896 nt and encodes a protein of 632 amino acids. Immunoblots with antibodies elecited against the purified glycoprotein from virus particles reacted with a fusion protein produced in Escherichia coli, indicating that the cloned ORF encodes the G protein. The 5' end of the G protein mRNA corresponds to nt 5111, relative to the 3' end of the viral (minus sense) genome, as determined by primer extension from mRNA isolated from infected plants, and extends to nt position 7155 on the genomic RNA. A 34-nt untranslated 5' leader sequence and a 115-nt untranslated 3' end flank the ORF on the mRNA. The gene junctions on either side of the G gene on the genomic RNA are identical to those previously described for other SYNV genes and are similar to sequences separating genes of animal rhabdoviruses. The predicted molecular weight of the G protein is 70,215 Da, a value less than the 77,000 Da estimated for the glycosylated G protein from virus particles. The deduced amino acid sequence of the SYNV G protein shares little direct relatedness with the G proteins of other rhabdoviruses, but appears to contain a similar signal sequence, a transmembrane anchor domain, and glycosylation signals. In addition, the SYNV G protein contains a putative nuclear targeting site near the carboxy terminus, which may be involved in transit to the nuclear membrane prior to morphogenesis. PMID- 1926780 TI - Characterization of infectious and defective cloned avian hepadnavirus genomes. AB - The infectivity in vivo, replication competence in vitro, and expression of viral genes of several molecularly cloned duck hepatitis B virus (DHBV) genomes were investigated. In addition, replication competence, core protein expression, and secretion of viral proteins were investigated for a grey heron hepatitis B virus genome. Except two, all DHBV isolates tested induced a systemic infection in Pekin ducks when injected as cloned viral DNA into the liver. After transfection of chicken hepatoma cells, both defective DHBV genomes expressed intracellular nucleocapsid and pre-S envelope proteins and secreted DHBs/pre-S particles into the medium. One of the defective DHBV genomes and HHBV produced within the cells replicative intermediates encapsidated in core particles and secreted virions, whereas the other defective DHBV genome did not and was unable to efficiently encapsidate the RNA pregenome. Comparative sequence analysis was performed to identify potential amino acid changes in viral proteins of both defective DHBV genomes. The data obtained demonstrate that most cloned avian hepadnaviruses are infectious or replication competent and suggest defects in envelope, polymerase or encapsidation function, respectively, in two cloned DHBV genomes. PMID- 1926781 TI - Characterization of the genome of rice tungro bacilliform virus: comparison with Commelina yellow mottle virus and caulimoviruses. AB - Rice tungro disease is caused by an infection of two different viruses, rice tungro spherical virus (a (+) sense RNA virus) and rice tungro bacilliform virus (RTBV) with a genome of circular double-stranded DNA. The genome of an RTBV isolate from the Philippines was cloned, sequenced, and found to be 8000 bp in length. It contains four open reading frames (ORFs) on a single strand, with ORF 1 having an internal termination codon (TAA). The 5' and 3' ends of a polyadenylated viral RNA transcript, of genome length, were mapped by primer extension and cDNA sequence analysis, respectively. The transcript is terminally redundant by 265-268 nucleotides. Purified virus particles contain two major proteins with molecular masses of 37 and 33 kDa, although only the 37-kDa protein was detected in the infected rice tissues. The N-terminal amino acid sequence of the 33-kDa protein was determined and its coding region was identified on the RTBV genome. The identity of the coat protein gene was further confirmed by expressing a region of the genome in Escherichia coli, the products of which reacted with anti-RTBV antibody. The unusually long ORF 3 of RTBV is predicted to encode a polyprotein of 194.1 kDa that includes: the coat protein(s), viral proteinase, reverse transcriptase, and ribonuclease H. The sections of the polyprotein show varying degrees of similarity to the counterparts of Commelina yellow mottle virus (a member of the proposed badnavirus group) and caulimoviruses. The functions of the other three ORFs are unknown. PMID- 1926782 TI - Deletion analysis of functional domains in baculovirus-expressed adenovirus type 2 fiber. AB - Various forms of Ad2 fiber were expressed in insect cells using recombinant baculoviruses and phenotypically characterized with respect to the following properties: trimerization, binding to penton base, nuclear targeting, and glycosylation. The morphology and dimensions of full-length fiber produced by invertebrate cells were indistinguishable from those observed in extracts from lytically infected mammalian cells. The domain required for trimer formation was mapped to the C-terminus, between amino acids 541 and 582. The N-terminal domain, between amino acids 1 and 16, negatively influenced the trimerization efficiency. Fiber gene products reduced to the shaft portion of the fiber capsomer formed significant amounts of stable dimers. Recognition with penton base only occurred with trimeric forms of fiber and was apparently not affected by deletion of the first 60 amino acids from the N-terminus. Fiber deleted of the Met1-Gly60 sequence was found to localize within the nucleus at levels similar to those of full-length fiber. All recombinant fibers, including tail-and-know-deleted forms, were found to be glycosylated using three separate assays, (i) in vivo labeling with [3H]glucosamine, (ii) binding to WGA, and (iii) reaction with monoclonal antibody RL2 directed against O-GlcNAc-containing glycopeptide. This implied that Ad2 fiber is a substrate for GlcNAc O-seryl transferase in insect cell cytoplasm and that at least one major glycosylation site is located in the shaft domain, between Met61 and Asn410. PMID- 1926783 TI - Upstream sequences within the terminal hairpin positively regulate the P6 promoter of B19 parvovirus. AB - For the B19 parvovirus P6 promoter, a 96-nt minimal truncation mutant retained activity in transient reporter gene assays. Deletion of sequences further upstream from this minimal promoter markedly diminished reporter activity in certain cell lines. This upstream region lies within the terminal hairpin from 249 to -157 and contains a 14-nt sequence that is protected by DNase I footprinting. The exact sequence is directly repeated further within the hairpin, suggesting a regulatory role. The hairpin termini of parvoviruses were known to serve as origins of replication and to catalyze virion packaging. We now suggest that, in addition to these functions, they exert cis-acting effects on B19 P6 promoted gene expression. PMID- 1926784 TI - sRNA of phage phi 29 of Bacillus subtilis mediates DNA packaging of phi 29 proheads assembled in Escherichia coli. AB - The structural genes of the prohead of phage phi 29 of Bacillus subtilis and a small phi 29 RNA (sRNA) were cloned and expressed in Escherichia coli individually or in combination to study the role of the sRNA in prohead assembly and the mechanism of prohead morphogenesis. The genes coding for the proteins of the scaffold (gp7), the capsid (gp8), the portal vertex (gp10), and the dispensable head fiber (gp8.5) were expressed in E. coli and the gene products were assembled, with and without the presence of the sRNA, into uniform and prolate particles that resembled the typical native phi 29 prohead. No differences in particle size and shape were found between the particles of 7-8 8.5-10 (scaffold-capsid-fiber-portal vertex) and 7-8-8.5-10-RNA (scaffold-capsid fiber-portal vertex-RNA), suggesting that the phi 29 sRNA was not required for phi 29 prohead assembly. The 7-8-8.5-10 particles produced in E. coli in the absence of phi 29 sRNA were fully competent to package phi 29 DNA in the defined in vitro DNA packaging system by the addition of purified sRNA. Moreover, these DNA-filled heads were assembled into infectious virions in extracts. Without the addition of the sRNA, the 7-8-8.5-10 particles were incompetent while the 7-8-8.5 10-RNA particles were competent in DNA packaging. Bacterial sRNA present in E. coli cannot substitute for the phi 29 sRNA. The assembly of prohead particles in E. coli indicated that host factors unique to B. subtilis were not required. The evidence that the phi 29 sRNA was not required for phi 29 prohead assembly and was not a fixed structural component of the phi 29 prohead favors the conclusion that the phi 29 sRNA is a specific enzyme or morphogenetic factor in DNA packaging. PMID- 1926785 TI - Antitermination of vaccinia virus early transcription: possible role of RNA secondary structure. AB - Transcription of vaccinia early genes by the viral RNA polymerase terminates downstream of a signal sequence TTTTTNT in the nontemplate DNA strand. Signal recognition occurs at the level of the sequence UUUUUNU in nascent RNA and depends on a virus-encoded termination factor (VTF). The presence of TTTTTNT elements within protein encoding regions of some early genes requires that these 5' proximal signals be ignored in order to achieve early expression of the full sized proteins. In the case of the A18R gene, which contains a proximal terminator that is not utilized in vivo (Pacha et al., J. Virol. 64, 3853-3863 (1990)), the TTTTTNT sequence can be folded into a potential hairpin structure such that UUUUUNU would be part of a duplex stem in the nascent RNA. We find that the A18R putative hairpin is unable to promote factor-dependent termination in a purified in vitro transcription system. Sequence manipulations that abrogate the potential to form an RNA hairpin restore the activity of the TTTTTNT motif. The in vitro studies suggest that antitermination at the proximal site of the A18R gene may be mediated by secondary structure in the nascent RNA, and that early termination involves recognition by VTF and/or RNA polymerase of the UUUUUNU sequence in single-stranded form. PMID- 1926787 TI - Nucleotide sequence of RNA 3 of peanut stunt cucumovirus. AB - The nucleotide sequence of the RNA 3 of the peanut stunt virus strain J (PSV-J) was determined and compared with those of the cucumber mosaic virus strain Y (CMV Y, subgroup I) and the tomato aspermy virus strain C (TAV-C) at both the nucleotide and protein levels. The RNA 3 of PSV-J consists of 2186 nucleotides and has two large open reading frames (ORFs). By analogy to other tripartite plant viruses, it is presumed that the first ORF (867 nucleotides) codes for the 3a protein and the second ORF (654 nucleotides) is the cistron of the coat protein which is expressed from subgenomic RNA 4 of 1010 nt residues. At the nucleotide level, PSV-J RNA 3 shows 60.6% homology to RNA 3 of CMV-Y and 66.3% to that of TAV-C, much lower than the value between the two CMV subgroups. For the 3a proteins there is 65.4% homology between PSV-J and CMV-Y and 70.2% homology between PSV-J and TAV-C. Although it has been known that PSV shows a distant serological relationship to CMV, the coat protein of PSV-J shows only 50% homology with that of CMV-Y. PMID- 1926786 TI - Association of hepatitis B viral precore mutations with fulminant hepatitis B in Japan. AB - We studied the precore DNA sequences of hepatitis B viral genomes in five patients with fulminant hepatitis B and in five with acute self-limited hepatitis B from Japan. Using the polymerase chain reaction, three to four independent HBV DNA clones from each patient were obtained and analyzed. We demonstrated that patients with fulminant hepatitis B carried HBV genomes with a G to A mutation at nucleotide positions 1898 (five of five patients; 18 of 18 clones, 100%) and 1901 (five of five patients; 12 of 18 clones, 66%) in the precore region. The first mutation results in an in-phase stop codon (TAG) in the precore open reading frame and the absence of HBeAg production. In contrast, a G to A mutation was found in 6 of 16 clones (37%) in position 1898 and in 0 of 16 clones (0%) in position 1901 from patients with acute self-limited hepatitis. We concluded that both of the precore mutations are commonly associated with fulminant hepatitis B and may contribute to the pathogenesis of fulminant hepatitis. A hypothetical model for the biological significance of these two mutations is proposed. PMID- 1926788 TI - Comparison of the 5' and 3' termini of tomato ringspot virus RNA1 and RNA2: evidence for RNA recombination. AB - The sequences of the 5' terminal 1140 and 3' terminal 1546 nt of tomato ringspot virus (TomRSV) RNA1 have been determined. These sequences share a high degree of nucleotide sequence similarity with the previously determined TomRSV RNA2 sequence. Eighty-eight percent of the 5' terminal 907 nt of TomRSV RNA1 and RNA2 contain identical nucleotide residues; the first 459 nt are identical at all positions, whereas the next 447 nt are identical at only 75.8% of the nucleotide positions. The region of similarity includes not only the 5' nontranslated leader but also sequence probably encoding polyproteins. The 3' terminal 1533 nt of TomRSV RNA1 and RNA2 are identical and are noncoding. The sequences common to RNA1 and RNA2 account for almost 35% of the total genomic sequence. It is possible that the similar sequences at both ends of TomRSV RNA1 and RNA2 are a result of recombination between these two genomic RNA components. PMID- 1926789 TI - Influenza virus ts61S hemagglutinin is significantly defective in polypeptide folding and intracellular transport at the permissive temperature. AB - The influenza virus hemagglutinin (HA) temperature-sensitive (ts) mutant, ts61S, contains a nucleotide change in RNA segment 4 which leads to an amino acid change at HA1 residue 110 of serine to proline. When ts61S HA is synthesized and maintained at the nonpermissive temperature (39.5 degrees), the HA is defective in transport in the exocytic pathway and is retained in the endoplasmic reticulum (S. Nakajima, D. J. Brown, M., Ueda, K., Nakajima, A. Suguira, A. K. Pattnaik, and D. P. Nayak, 1986, Virology 154, 279-285). In a comparison of the biochemical properties of ts61S HA and A/WSN/33 HA (wt) expressed at the permissive temperature (33 degrees), we have found that ts61S HA is extensively debilitated. A large proportion of ts61S HA fails to gain reactivity with conformation specific monoclonal antibodies and does not become resistant to protease digestion. In turn, a large population of the molecules are not transported from the ER to the Golgi apparatus or cell surface with the same kinetics or efficiency as wt HA. These data suggest that the serine to proline change at HA1 residue 110 leads to partial impairment of folding at the permissive temperature with complete impairment at the nonpermissive temperature. PMID- 1926790 TI - cDNAs of beet necrotic yellow vein virus RNAs 3 and 4 are rendered biologically active in a plasmid containing the cauliflower mosaic virus 35S promoter. AB - cDNAs of beet necrotic yellow vein virus RNAs 3 and 4 could be rendered biologically active when they were placed under the control of the cauliflower mosaic virus 35S promoter and polyadenylation signal. Although the 35S in vivo transcripts should have contained up to forty 5' and several hundred 3' nonviral nucleotides, the progeny viral RNAs had the same sizes as in naturally infected sugarbeets. The progeny RNAs did not hybridize with the nonviral sequences indicating that they were apparently not replicated. Deletion and insertion mutants of RNA 3 cDNA clones were also biologically active in plants but a plasmid which contained the cDNA of RNA 3 in antisense orientation was not. The biological activity of plasmid DNAs compared with the corresponding synthetic transcripts is discussed. PMID- 1926791 TI - Role of alfalfa mosaic virus coat protein in regulation of the balance between viral plus and minus strand RNA synthesis. AB - Replication of wild type RNA 3 of alfalfa mosaic virus (AIMV) and mutants with frameshifts in the P3 or coat protein (CP) genes was studied in protoplasts from tobacco plants transformed with DNA copies of AIMV RNAs 1 and 2. Accumulation of viral plus and minus strand RNAs was monitored with strand-specific probes. A frameshift in the P3 gene did not change the asymmetry in plus/minus strand accumulation observed for the wild type. A frameshift early in the CP gene resulted in a 100-fold reduction in plus strand accumulation and a 3- to 10-fold increase in minus strand accumulation. A frameshift late in the CP gene caused a similar reduction in plus strand accumulation but had no effect on minus strand accumulation. This latter mutant accumulated nearly wild type levels of a truncated CP molecule. Apparently, wild type AIMV CP up-regulates plus strand accumulation and down-regulates minus strand accumulation and these two functions can be mutated separately. PMID- 1926792 TI - Dengue virus premembrane and membrane proteins elicit a protective immune response. AB - We have constructed recombinant vaccinia viruses that express the premembrane (pre-M), membrane (M), or the cleaved, residual portion of pre-M (non-M) proteins of dengue 4 virus, or the pre-M, non-M, or envelope (E) proteins of dengue 2 virus, to evaluate their ability to induce protective immunity in mice. Cells infected with these recombinants make proteins of expected size. Mice immunized with recombinants expressing dengue 4 pre-M or M were protected against subsequent dengue 4 encephalitis challenge, but non-M was not protective. However, a recombinant that expressed both pre-M and E as a polyprotein gave solid protection, while the simultaneous administration of the two recombinants expressing pre-M and E gave a significant level of protection. Pre-M and M function as antigens eliciting a protective immune response, and the combination of pre-M plus E is more protective than E alone. PMID- 1926793 TI - [The bitemporal use of a UHF electrical field (27.12 MHz) in the early recovery period of acute cerebral circulatory disorders: the viscous-elastic properties and microcirculation of the blood]. AB - UHF electric field (27 or 12 MHz) was applied in intermittent regimen and nonthermal dosage by means of bitemporal condensation plates in early terms after cerebrovascular accident in 40 recovering patients. Clinical response was achieved in 60% of patients who had underwent physiotherapy alone and 75% of those who had been exposed to the electric field in combination with therapeutic exercise and massage. Investigations of microcirculation, blood viscosity and elasticity showed positive changes in the above parameters which could underlie beneficial effect of the field. The paper presents discussion on the effect of such physiotherapy on blood rheology. PMID- 1926794 TI - [The central hemodynamic reaction of patients with ischemic heart disease to the climatic and weather conditions of an arid zone]. AB - Central hemodynamics of coronary patients living in the arid zone (215 males aged 40-72 and 150 females aged 40-75) was assessed in comfortable weather conditions, 1-2 days before the invasion of the dust storm, upon its invasion and in hot weather season (+26-30 degrees C). Angina of effort functional class I, II and III was in 102, 198 and 65 patients, respectively. Atmospheric conditions before the invasion of the dust storm form a hypoxic type of weather while on the day of the storm the weather appears spastic resulting in arterial hypertension, elevated total peripheral resistance and heart beat in diminution of cardiac output and stroke volume. Hot weather brings about a hypotensive response, total peripheral resistance falls, cardiac output increases at the expense of enhanced heart beat as stroke volume decreases. It is concluded that under the climatic conditions of an arid zone coronary patients develop a complex of hemodynamic responses which function with strain to supply blood to organs and tissues. PMID- 1926795 TI - [The dynamics of the data on the hemogram and blood biochemical indices in pulmonary tuberculosis patients undergoing peloid therapy]. AB - When treated with adjuvant peloids (peloidin, gumizol, torfot), tuberculosis patients demonstrated a positive trend in biochemical parameters. Therapeutic benefit shown by rapid recovery of blood picture was attributed to antiinflammatory and resolving effect of pelotherapy. PMID- 1926796 TI - [The developmental problems in medical technology for physiotherapy]. PMID- 1926797 TI - [The effect of mineral water on hormone secretion in patients following cholecystectomy]. AB - Hypersecretion of hydrocortisone, that of insulin, triiodothyronine, thyroxin reflecting phases of stress response and persistence were recorded in early and late postcholecystectomy terms, respectively. As intake of mineral water stimulates secretion of anabolic hormones (insulin, triiodothyronine and thyroxin) and inhibits secretion of catabolic hormone hydrocortisone, drinking of mineral water can be helpful in activation and adjustment of compensatory and adaptive responses after cholecystectomy. PMID- 1926798 TI - [The effect of a course of naftusia water intake on the gastroenteropancreatic endocrine system]. AB - Intake of naftusia mineral water influences insulin, glucagon and gastrin secretion measured in patients with chronic acalculous cholecystitis in the following manner: initial low insulin and glucagon, normal gastrin levels rise; initial elevated gastrin and normal glucagon lower at the start of the treatment. The course of naftusia crenotherapy resulted in adaptation to water intake as evidenced by normalization of high gastrin, low glucagon levels in minimal rise of insulin. PMID- 1926799 TI - [The characteristics of using mineral waters with an increased boron content in rehabilitating patients with hepatobiliary pathology]. AB - Changes in biochemical bile composition were investigated in 42 patients with chronic infective acalculous cholecystitis on combined sanatorium treatment. In those with carbohydrate dysbolism, bile production was found inhibited possibly due to the intake of carbonate sodium mineral water of moderate mineralization containing bromine and fluorine with high concentrations of bromine, in particular. PMID- 1926800 TI - [The differentiated use of mitigating mud therapy in the early convalescent period of viral hepatitis]. AB - Two new techniques of mitigatory pelotherapy using mud applications to paravertebral area and acupuncture were compared for 152 viral hepatitis convalescents. The efficacy of the treatment was shown by a wide spectrum of hepatic functional and immunologic reactivity indications. PMID- 1926801 TI - [Acupuncture in the treatment of gastroenteric diseases in children]. AB - Individual regimens of acupuncture were applied in treatment of 66 children with various gastrointestinal diseases. As a result, the effect of the combined treatment rose 1.4-fold. PMID- 1926803 TI - [Vibrotherapy in the treatment of the sequelae of spinal cord trauma and diseases]. PMID- 1926802 TI - [The dynamics of the brain bioelectrical activity in patients with ischemic stroke undergoing the electrophoresis of antiaggregant preparations and carbonate baths]. PMID- 1926804 TI - [Physiotherapy in the rehabilitation of patients with compression-ischemic neuropathies]. PMID- 1926805 TI - [The climatotherapy of catarrhal gingivitis in children at a health resort]. PMID- 1926807 TI - [The use of ultrasonic and low-frequency alternating magnetic fields in treating diseases of the locomotor apparatus]. PMID- 1926806 TI - [The experience of using ergotherapy in patients with bronchial asthma due to physical effort]. PMID- 1926808 TI - [Therapeutic physical exercise in traumatic spinal cord lesions]. PMID- 1926809 TI - [Physical factors in the treatment and rehabilitation of patients with the neurogenic form of impotence]. PMID- 1926810 TI - [The neurophysiological and neurochemical mechanisms of the analgesic action of transcutaneous electrostimulation]. PMID- 1926811 TI - [Characteristics of peptide preparations obtained during enzymatic hydrolysis and ultrafiltration of milk proteins for use in specialized nutrition products]. AB - +Ultrafiltrated bovine milk proteins with whey protein/casein ratios 20/80, 60/40 and 97/3 were subjected to pancreatin hydrolysis, and the hydrolysates obtained were fractionated to high- and low-molecular weight (LMW) fractions by means of ultrafiltration. The preparations obtained were characterized according to routine physico-chemical indices, amino-nitrogen content, amino acids score, molecular weight distribution, and concentration of precipitating milk antigens. The capacity of LMW fractions for inducing oral anaphylactic sensitization in guinea pig and for changing its susceptibility to histamine LD50 was studied. The conclusion has been made that LMW preparations with whey/casein ratios 20/80 and 60/40 could be effectively used in specialized formulae intended for nutrition of allergic children and adults, nursing women, and also for enteral nutrition. PMID- 1926812 TI - [Study of nutritive value of modified casein]. AB - It has been shown that modified casein purified from carbohydrate components contains several times less phosphorus and calcium as compared to initial casein. Figures close to experimental and potential biological value were obtained in experiments on growing rats with modified and initial casein as a protein component-milk substitute. PMID- 1926813 TI - [Problem of assimilation of isolated fish protein]. AB - Ion-exchange chromatography was used to study the content of free amino acids in the blood serum of the portal and hepatic veins 0.5, 1, 2 and 3 h after oral administration of isolated fish protein (IFP) to white rats. The rate of IFP decomposition was estimated in the system of immobilized enzymes. It has been found that all amino acids of IFP are accessible and well assimilated in the body. Concentrations of arginine, lysine, ornithine, ramified and aromatic amino acids reached their maximum values more rapidly after administration of IFP than casein. However, the process of IFP production led to the reduction of the isolate digestion rate under the effect of peptidases as compared to the untreated fish and casein, as the result of which the total content of IFP amino acids in the blood was decreased 2 h after IFP administration, and the time of the isolated protein digestion in the body was extended. PMID- 1926814 TI - [Characteristics of sodium metabolism in rats with experimental hypertension caused by chronic alimentary imbalance]. AB - Beginning from 1.5 month of life Wistar rats were kept under conditions of chronic 1 and 2% salt loading combined with a low-protein diet (6-8% of protein VS, as compared with 23-24% in the normal diet). At the age of 14-16 months when a stable hypertension developed due to the above alimentary imbalance, their sodium metabolism was studied using whole-body radiometry with 22Na. A three chamber model of 22Na metabolism was developed for the analysis of 22Na excretion from the body. This helped in establishing the heterogeneity of sodium metabolism in experimental animals. Besides that, it has been shown that not only sodium retention in the body, but also its redistribution between intra- and extravascular sections play an important role in the development of hypertension. Protein deficiency in the diet aggravates sodium metabolism disorders in experimental animals. PMID- 1926815 TI - [Diabetes mellitus as primary generalized pathology of the active transmembrane transport of glucose (a new concept)]. PMID- 1926816 TI - [Detection of bacteria of the genus Erwinia in sanitary- microbiological control of dry milk products for infants]. AB - The possibility of identification of Erwinia bacteria was established during the microbiological analysis of child nutrition products, containing vegetable components, for the presence of coliform bacteria. Biochemical and cultural physiological properties differentiating Erwinia herbicola from Enterobacter agglomerans were studied, and the most significant differential-diagnostic tests for bacteria identification were determined. To identify Erwinia bacteria that do not belong to coliform bacteria the following additional tests are recommended for practical use at the sanitary-bacteriological laboratories: the presence of yellow or brown pigment during the growth in Endo medium; inoculation into nutrient agar medium with saccharose; inoculation into gelatin -containing medium. PMID- 1926817 TI - [Nitrates in cow's milk and in various milk products in the Ukraine]. AB - The results of the investigations conducted have shown that most milk samples analyzed contained from 2 to 55.2 mg/l nitrates (P50 = 27.2 mg/l), dried milk and dry milk mixtures contained from 56.5 to 91.0 mg/kg nitrates (P50 = 72.9 mg/kg). The amount of nitrates detected in most products prepared at special milk centers for child nutrition did not exceed the mean level of nitrates in the whole milk. However, 12% of milk samples and 6% of dry milk mixtures contained significantly higher levels of nitrates. A conclusion has been made on the necessity of testing and regulation of nitrate content in the milk and milk products for child nutrition. PMID- 1926818 TI - [Analytical evaluation of protein quality of new food products]. PMID- 1926819 TI - [Determining the levels of staphylococcal enterotoxins types A and B in food products by the immunoenzyme method]. AB - "Sandwich" variant of ELISA was used to identify staphylococcal enterotoxins (SE), types A and B, in S. aureus filtrates inducing food poisoning, in extracts of the lactic acid product for infants "Biphilin" that caused staphylococcal infection, and in foods contaminated with SE in varying concentrations. It has been shown that ELISA used for SE identification in foods permits revealing SE, types A and B, in liquid products in concentrations of 1-2 ng/ml (that is 1000 fold more sensitive, than the immunodiffusion test, 400-800-fold more sensitive than the passive hemagglutination test, and 10-fold more sensitive than the indirect passive hemagglutination test), and in solid products--in concentrations of 5-10 ng/g (after artificial contamination). PMID- 1926820 TI - [Determining riboflavin level in urine (comparative analysis of the methods)]. AB - Four methods of riboflavin content estimation in urine were studied: they are based on specific titration of vitamin B by riboflavin-binding protein (1), riboflavin decomposition by boiling in alkali (2), riboflavin fluorescence suppression by dithionate (3), and high-performance liquid chromatography. A conclusion has been made on the necessity of a home standard for riboflavin estimation by methods 1-3. The results obtained with the above methods correlated well, regression equations were derived describing correlation of these results. Methods 1 and 3 are most simple and highly specific and sensitive, therefore they could be recommended for wide use in large-scale clinical investigations. PMID- 1926821 TI - [Use of high performance liquid chromatography for analysis of vitamin A in food products]. AB - High-performance liquid chromatography (HPLC) was used for vitamin A assay in foods and raw materials. Metrological characteristics of this method have been estimated: relative standard deviation was 0.06-0.08, average recovery of vitamin A was 97.3 +/- 2.6 with n = 6, P = 0.95). The statistical analysis of the results obtained with HPLC has shown that it could be successfully used for vitamin A assay in varying foods containing no less than 0.01 mg of vitamin A per 100 g. PMID- 1926822 TI - [Effect of storage on microbiological indicators in oysters]. PMID- 1926823 TI - [A triangular nomogram for calculating individual pattern of nutrition]. PMID- 1926824 TI - [Characteristics of nutrition and metabolism in patients with post-burn esophageal strictures]. PMID- 1926825 TI - [Botulism and various problems of prevention of its unfavorable outcomes]. PMID- 1926826 TI - [Effect of dietary proteins on the blood level of cholesterol]. PMID- 1926827 TI - Current status of fibronectin in transfusion medicine: focus on clinical studies. AB - It has long been hypothesized that fibronectin (Fn) is essential to the function of the reticuloendothelial system (RES) and that the reversal of Fn deficiency in critically ill patients would result in a clinical benefit to these patients. Fn administration to deficient patients was postulated to improve the function of the RES, decrease the incidence of organ failure, sepsis and ultimately mortality. Over the past 15 years, several clinical studies have been performed to test these hypotheses. The initial anecdotal studies using cryoprecipitate (a plasma fraction enriched in Fn) revealed promising results but were neither controlled nor blinded. Further controlled studies were published utilizing both cryoprecipitate and purified Fn. Unfortunately, the great majority of authors found no beneficial effects of Fn administration in critically ill patients, in relation to incidence of organ failure, sepsis, or mortality. These results do not support the use of Fn in this setting. Fn utilization in wound healing has shown promising results in case reports. Although its role in wound healing is not yet fully delineated, initial reports with corneal wounds show a beneficial influence of Fn administration. Further studies are needed to determine the exact function(s) of Fn in a healing wound. Efficacy must still be shown in controlled clinical trials; dosing and administration regimens need to be elucidated. PMID- 1926828 TI - Leukocyte filtration removes infectious particulate debris but not free virus derived from experimentally lysed HIV-infected cells. AB - We used in vitro model of storage-induced leukocyte degradation in blood to experimentally characterize the infectivity of the debris of lymphocytes harboring human immunodeficiency virus (HIV-1). The leukocyte filtration process removed both intact HIV-infected H9 cells and the particulate debris, but failed to remove the cell-free HIV released from lysed cells. These data suggest that the leukocyte filtration of donor blood soon after collection would optimally reduce the particulate infectious burden of blood for transfusions. PMID- 1926829 TI - Results of tests with different cellular bioassays in relation to severity of RhD haemolytic disease. Report from nine collaborating laboratories. AB - Nine different laboratories collaborated in testing sera containing anti-D using various assays with antibody-coated red cells, including antibody-dependent cell mediated cytotoxicity, either with monocytes (ADCC(M)) or K-lymphocytes (ADCC(L)), monocyte-mediated chemiluminescence and adherence to, and phagocytosis by, peripheral monocytes, U937 cells or cultured macrophages. The samples tested included 14 from 11 mothers of infants with Rh haemolytic disease, 2 monoclonal anti-Ds and 3 samples containing hyperimmune anti-D. The results of the bioassays were graded on a scale of 1-3, as were the degrees of severity of haemolytic disease; results were regarded as correct when the grades of the bioassay result and of the degree of severity were the same. Overall, correct results were obtained with the various assays as follows: ADCC(M), 60%; ADCC(L), 57%; chemiluminescence, 50%; adherence and phagocytosis with peripheral monocytes, 41% (but 71% in one laboratory), and with U937 cells or cultured macrophages, 32%. The ADCC(M) assay, compared with the ADCC(L) assay, not only gave better correlations with the severity of haemolytic disease but also gave higher grades of results with hyperimmune sera and with the monoclonal anti-Ds. Because many of the samples tested were taken after delivery rather than during pregnancy, and because of variations between laboratories, the present results do not conclusively establish the superiority of the ADCC(M) assay in predicting the severity of Rh haemolytic disease. PMID- 1926830 TI - Brb, a platelet alloantigen involved in neonatal alloimmune thrombocytopenia. AB - Serum from a pregnant woman with the May-Hegglin anomaly contained a platelet specific antibody. The serum reacted in the platelet indirect immunofluorescence test (PIIFT) with 97.6% of random donor platelets and those of the father but not with the mother's own platelets. This antibody induced a moderate thrombocytopenia in the infant that responded to infusion of intravenous immunoglobulin concentrates. The platelet phenotypes were PLA1+, Baka+, Bra+/Brb- for the mother, PLA1+, Baka+, Bra-/Brb+ for the father, and PLA1+, Bra+/Brb+ for the neonate. Analysis of the maternal serum with an immunoassay based on monoclonal antibody immobilization of platelet antigens (MAIPA) and immunoprecipitation techniques demonstrated the absence of antibodies directed against HLA class I antigens and that the antigen recognized was located on the platelet-GpIa/IIa complex. This antigen was present on 113/115 random donor platelets, in 7 of the 7 unrelated May-Hegglin platelets, and only absent in 3/24 Bra+ individuals, including the mother. No platelet-specific antibody was present in the serum of the 7 unrelated May-Hegglin subjects. The antigen recognized by this platelet-specific antibody thus meets the criteria defining the antithetic allele of Bra, i.e. the Brb alloantigen. PMID- 1926832 TI - Right lateral decubitus position via skin pressure vegetative reflex may prevent anxiety, adverse autonomic reactions, and syncope in blood donors. PMID- 1926831 TI - HIV-1-Ag as the one marker in the early stage of HIV-1 infection. PMID- 1926833 TI - Neonatal alloimmune thrombocytopenia due to anti-Brb (HPA-5a). Report of three cases in two families. PMID- 1926834 TI - Prevalence of hepatitis C virus antibody in beta-thalassemic polytransfused children in a long-term follow-up. PMID- 1926835 TI - The changing role and view of physicians. PMID- 1926836 TI - Adenocarcinoma of the small intestine in Crohn's disease: a unique finding. AB - Development of adenocarcinoma of the small bowel is rare. We present this report of a patient with a long-standing history of Crohn's disease who was found to have the 95th reported case of adenocarcinoma developed in the presence of Crohn's. The unique feature of this case is the finding of two distinctly separate carcinomas in the same surgical specimen. With report of this case and a review of the literature, certain characteristics are presented in hopes of raising suspicions sufficiently to detect this malady at an earlier stage. PMID- 1926837 TI - The successful resuscitation of a hypothermic multitrauma patient. AB - Accidental hypothermia due to exposure is an infrequent cause of circulatory arrest. A premature diagnosis of clinical death must be avoided in these patients and vigorous attempts at active rewarming are indicated. Extracorporeal circulation in the form of partial cardiopulmonary bypass has been reported as an effective means of rapid, even core rewarming. We wish to report a recent case at Ruby Memorial Hospital in which extracorporeal circulation was used successfully in resuscitating a profoundly hypothermic multi-trauma victim. PMID- 1926839 TI - The GNP and brainwashing. PMID- 1926838 TI - Fish stings and other marine envenomations. AB - West Virginia, it would seem, is an unlikely place for physicians to encounter patients with poisonous marine envenomations. To the contrary, West Virginias who vacation at the beach may be envenomated and require further evaluation and treatment when they return home. Likewise, certain aquarium pets or even freshwater fish may envenomate those who have contact with them. Such underwater sea creatures can cause local and systemic toxic or allergic reactions which potentially can be serious. This article describes these possible toxic encounters as well as first aid and medical management. PMID- 1926840 TI - Discount medicine. PMID- 1926841 TI - Domestic violence. Risk factors and outcomes. AB - Domestic violence is a pervasive and frequently unrecognized cause of injury among women. We reviewed data from standardized interviews with 218 women who presented to an emergency department with injuries due to domestic violence. Victims ranged in age from 16 to 66 years and constituted a wide range of socioeconomic and ethnic backgrounds. Domestic violence often resulted in severe injury; 28% of the women interviewed required admission to hospital for injuries, and 13% required major surgical treatment. The typical presentation was injuries to the face, skull, eyes, extremities, and upper torso. A third of the cases involved a weapon, such as a knife, club, or gun. In all, 10% of the victims were pregnant at the time of abuse, and 10% reported that their children had also been abused by the batterer. Most victims (86%) had suffered at least one previous incident of abuse, and about 40% had previously required medical care for abuse. Victim recognition and referral to appropriate agencies could be improved if primary care physicians were more aware of the prevalence, severity, frequency of occurrence, and typical presentation of domestic violence. PMID- 1926842 TI - The incidence of Chlamydia pneumoniae lower respiratory tract infections among university students in northern California. AB - Chlamydia pneumoniae has recently been identified as a cause of lower respiratory tract infections. From March 1987 to March 1988, 259 university students-151 students with lower respiratory tract infections and 108 controls-from the University of California, Berkeley, were studied to determine the incidence and pattern of C pneumoniae lower respiratory tract infections. Serologic evidence of a recent C pneumoniae infection was found in less than 2%, and the organism was not isolated from any of the subjects. Despite the paucity of evidence of a recent infection, 47.5% of this university population showed serologic evidence of a previous C pneumoniae infection. The lower incidence of C pneumoniae infection in our population, when compared with previous reports, suggests that there may be geographic and temporal differences or fluctuations among populations. PMID- 1926843 TI - Student perceptions of mistreatment and harassment during medical school. A survey of ten United States schools. AB - Senior students at 10 medical schools in the United States responded to a questionnaire that asked how often, if ever, they perceived themselves being mistreated or harassed during the course of their medical education. Results show that perceived mistreatment most often took the form of public humiliation (86.7%), although someone else taking credit for one's work (53.5%), being threatened with unfair grades (34.8%), and threatened with physical harm (26.4%) were also reported. Students also reported high rates of sexual harassment (55%) and pervasive negative comments about entering a career in medicine (91%). Residents and attending physicians were cited most frequently as sources of this mistreatment. With the exception of more reports of sexual harassment from women students, perceived mistreatment did not differ significantly across variables such as age, sex, religion, marital status, or having a physician parent. Scores from the 10 schools also did not vary significantly, although the presence of a larger percentage of women in the class appeared to increase overall reports of mistreatment from both sexes. PMID- 1926845 TI - Tissue banking. AB - The Scientific Board of the California Medical Association presents the following inventory of items of progress in orthopedics. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in orthopedics that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Orthopedics of the California Medical Association, and the summaries were prepared under its direction. PMID- 1926846 TI - Ilizarov method. PMID- 1926847 TI - Update on the diagnosis and treatment of scaphoid fractures. PMID- 1926848 TI - Open reduction of pelvic fractures. PMID- 1926849 TI - Arthroscopic-assisted reconstruction of the anterior cruciate ligament. PMID- 1926850 TI - Bearing surfaces in total joint replacement. PMID- 1926844 TI - Autocrine growth factors and solid tumor malignancy. AB - The ability of malignant cells to escape the constraint that normally regulate cell growth and differentiation has been a primary focus of attention for investigators of cancer cell biology. An outcome of this attention has been the discovery that the protein products of oncogenes play a role in the activation of growth signal pathways. A second outcome, possibly related to abnormal oncogene expression, has been the discovery that malignant cells frequently show an ability to regulate their own growth by the release of autocrine growth modulatory substances. Most important, the growth of certain malignant cell types has been shown to depend on autocrine growth circuits. A malignant tumor whose continued growth depends on the release of an autocrine growth factor may be vulnerable to treatment with specific receptor antagonists or immunoneutralizing antibodies designed to break the autocrine circuit. Information is rapidly emerging concerning autocrine growth factors in selected human solid tissue malignancy. PMID- 1926851 TI - Percutaneous discectomy. PMID- 1926852 TI - Objective measurements for rehabilitation after back injury. PMID- 1926853 TI - Superior mesenteric artery thrombosis associated with antiphospholipid syndrome. PMID- 1926854 TI - Metastasis-induced acute pancreatitis. PMID- 1926855 TI - Spontaneous intracranial hypotension. An uncommon and underrecognized cause of headache. PMID- 1926856 TI - Radiologic case. Lung mass and hemoptysis in a patient with tuberculosis. PMID- 1926857 TI - The perils of providing medical opinion. A state medical association's experience. PMID- 1926858 TI - Medical education, training, and health care services in the Republic of Singapore. PMID- 1926859 TI - Understanding autocrine growth regulation. PMID- 1926860 TI - Abortion 'gag' rule. PMID- 1926861 TI - Do we need warning labels on food? PMID- 1926862 TI - [Noise origin and noise-induced complaints after heart valve replacement with mechanical prostheses]. AB - 143 patients were investigated in order to determine whether there is a difference in the intensity of the closing click between different mechanical heart valve prostheses. 35 had St. Jude Medical (SJM), 38 Duromedics Edwards (DE), 36 Bjork Shiley Monostrut (BSM) and 34 had Carbomedics prostheses implanted. Sound pressure level determined at 1 meter distance was significantly higher for the DE 33.5 +/- 6 dB(A) and BSM 31 +/- 4 dB(A) than for the SJM 24 +/- 4 dB(A) and CM 25 +/- 6 dB(A) prostheses (p = 0.0001). Valves developing higher sound pressures were more frequently audible for the patients (p = 0.0012), caused more sleep disturbances (p = 0.024) and more complaints during daytime (p = 0.07). Significantly more patients carrying such valves wished to have a less noisy valve implanted (0.0047). Symptomatic patients wear louder valves, were younger, had better hearing and were more frequently in sinus rhythm. Valve diameter correlated with the developed sound pressure level. 349 patients answered a questionnaire after valve replacement with DE (256) or BSM (93) prostheses. 5% registered their noise-related complaints as being severe, but more than one third wished to have a less noisy valve implanted. The noise created by the closing click of mechanical prostheses causes significant complaints and this factor should be considered when a mechanical valve is selected. PMID- 1926863 TI - [Suspicious findings in gynecologic cytodiagnosis]. AB - Our investigations were based on the occurrence of cervical smear cell pictures where definitive cytological evaluation regarding malignancy/atypia was impossible due to quality loss for different reasons. In a retrospective cross sectional study we analysed 216 histologically clarified cervical findings in 245 women whose cytological smears--out of a total of 277,677 smears over a 3-year period (1987-1989)--were placed in group III according to Papanicolaou (suspect malignancy/atypia or undetermined value). This subgroup of group III according to Papanicolaou amounted to 0.088% (on average 82 out of 92,559 smears a year) of the total amount of smears. The histological clarification of suspect or undetermined cytological cell pictures revealed a precancerous or cancerous condition in almost three quarters (72.2%) of the cases. Cervical intraepithelial neoplasia, grade III (CIN III) shows the highest prevalence at 40.3% (carcinoma in situ amounted to 22.2% and high-grade dysplasia 18.0%) and the subgroup "non malignancy" shows the second highest prevalence at 27.8% (regenerated epithelium- 18.5%, benign glandular changes--4.2%, abnormal epithelium--3.7%, others 1.3%). In cases of suspected malignancy/atypia or indeterminate cytological cell picture we strongly emphasize the necessity of clarification of the cervical canal findings by means of curettage when colposcopy of the ectocervix shows no pathological findings. Carcinoma in situ, high-grade dysplasia and regenerated epithelium are the most frequent causes of cytodiagnostic problems in those cases in which the quality of the cell picture is reduced. PMID- 1926864 TI - [Clinical and urodynamic results after various ileum neobladder procedures]. AB - Urinary diversion after cystectomy in 15 male patients suffering from advanced transitional cell carcinoma of the bladder (pT-pT3b) was performed by ileal neobladder in different ways: S type n = 5, U type n = 3, J type n = 3 and W type n = 4. The perioperative mortality was nil, the overall complication rate 60%. The patients were followed up by means of regular urodynamic controls after 3, 6 and 12 months. After a median follow up period of 18 months (12-29) the J type and W type seem to be superior with regard to postoperative continence. All patients with W type neobladder are continent. The capacity of the neobladders varies from 200 to 800 ml; the W pouches have the highest capacity. PMID- 1926865 TI - [Development of gynecologic-oncologic patient data records for after care]. PMID- 1926866 TI - Endothelium--thromboresistance. PMID- 1926867 TI - Endothelium-derived relaxing and contracting factors. AB - Since the description of the essential role of the endothelium in mediating relaxations due to acetylcholine in mammalian arteries, it has become obvious that endothelial cells release several relaxing and contracting substances. The release is activated by a variety of agents including circulating hormones, autacoids, and products liberated by aggregating platelets, but also by changes in shear stress exerted by the blood. There is strong evidence that the major endothelium-derived relaxing factor (EDRF) is the free radical nitric oxide (NO) formed enzymatically from L-arginine. Endothelium-dependent relaxations caused by EDRF are induced through increases in the activity of soluble guanylate cyclase in the smooth muscle. Other relaxing factors, such as prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) contribute to endothelium dependent relaxations. Beside the recently described and chemically identified peptide endothelin, at least two other endothelium-derived contracting factors appear to exist. The mechanisms by which endothelium-derived contracting factors activate vascular smooth muscle are not yet clear. In certain clinical situations an impairment of the production of EDRF in face of a maintained or augmented release of contracting factors may contribute to the occurrence of localized vasospasm or generalized increases in peripheral resistance. PMID- 1926868 TI - Thromboresistance of the arterial wall: the role of heparin and glycosaminoglycans. AB - Thromboresistance of the arterial wall is the result of many factors which dynamically interact with each other. Glycosaminoglycans (GAG), among which heparin, synthesized by endothelial cells, smooth muscle cells, and fibroblasts, play an important role in determining vessel wall non-thrombogenicity. We are describing morphological-morphometrical characterization (increase in endothelial cell density and nucleus/cytoplasm ratio) of bovine aortic endothelial cells grown in the presence of heparin and other GAGs. PMID- 1926869 TI - The mechanisms and significance of the coupled release of endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2) from endothelial cells. AB - Endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2) are co released from endothelial cells by stimuli acting via membrane-bound receptors or via non-receptor mediated mechanisms. The receptor-mediated release of EDRF and PGI2 is calcium-dependent and seems to be under the negative feedback regulation of protein kinase C. Significant interactions between EDRF and PGI2 or between their respective second messengers within the endothelial cell have not yet been conclusively demonstrated. Furthermore, although EDRF and PGI2 synergize in the inhibition of platelet aggregation, there is little evidence for such synergism in smooth muscle relaxation. These observations indicate that EDRF and PGI2 release may be coupled primarily by their requirement for raised intracellular calcium levels and by their regulation through protein kinase C. PMID- 1926870 TI - Recent developments in receptor binding radiopharmaceuticals. AB - The stereoselective and saturable binding between receptor and ligand molecules plays an important role in many biological processes. Therefore ligand-receptor interactions have been increasingly studied in recent years by means of radionuclide labelled ligand molecules of high radiochemical purity and high specific activity. This contribution describes radiochemical development work of such radioligands performed at the Austrian Research Centre Seibersdorf in recent years: Tc99m-Neo-Galacto-Albumin was prepared as ligand for the Hepatic Binding Protein receptor, I-123-Low Density Lipoprotein (LDL) for LDL-receptors in the liver. Since LDL is involved in the origin of atherosclerosis it was subsequently labelled with Tc99m and In-111 as well. A pyrrolidine-methyl-benzamide derivative was separated into its stereoisomers and the active form labelled with I-123. It exhibited specific uptake in Dopamine D-2 receptor containing brain tissue. A benzazepine derivative was likewise labelled with I-123 as potential ligand for D 1 receptors. PMID- 1926871 TI - Kinetic analysis. AB - With the aid of positron emission tomography the concentration of radioactivity labeled ligands can be measured as a function of time in small parts of the human body in vivo. The use of short lived isotopes enables repeated studies to be performed on the same subject within reasonable time. A basic tool in the analysis of such data is a tracer kinetic model which relates the time course of the radioligand in plasma to the time course of the radioligand in the tissue. The model takes into account transport between the blood and the tissue, specific binding and release from the receptors, and non-specific binding. From a fit of the model to the measured time course of the radioligand, the receptor density, the association rate constant, and the dissociation rate constant can be determined in small volume elements of the tissue. PMID- 1926872 TI - Quantification of human hepatic binding protein (HBP) via 99mTc-galactosyl neoglycoalbumin (NGA) liver scintigraphy. AB - 99mTc-galactosyl-neoglycoalbumin (99mTc-NGA) was synthesized by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. Injection of 99mTc-NGA (150 MBq; 3.5 mg (= 50 nmol)/ml demonstrated the liver to be the exclusive site of tracer-uptake. Simulation of 99mTc-NGA-kinetics allowed quantification of binding to the hepatic binding protein (HBP). Using this model we studied 250 patients with various liver disease. In alcoholic liver cirrhosis such patients with Child B and Child C stage cirrhosis had a lower HBP-concentration in the liver compared to control individuals (0.85-1.2 mumol/l). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP-concentration (0.20-0.45 mumol/l) than Child A patients (0.60-0.85 mumol/l; p less than 0.01) and Child B patients (0.45 0.60 mumol/l; p less than 0.05). In patients with biopsy proven liver fibrosis (0.80-1.22 mumol/l) no difference in receptor concentration to normal individuals was estimated. Patients with recently diagnosed acute viral hepatitis underwent repeated 99mTc-galactosyl-neoglycoalbumin (NGA) scanning of the liver during the course of the disease. Return of liver function tests to normal values was associated with an increased hepatic imaging size as well as increase in HBP concentration (up to a 3-fold of initial concentration). In patients exhibiting a prolonged course of the disease changes in NGA-kinetic data were borderline and the hepatic image size unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1926873 TI - Low density lipoprotein receptors: preliminary results on "in vivo" study. AB - Plasmatic levels of low density lipoproteins (LDL) are regulated by the receptor pathway and most LDL receptor are located in the liver. A receptor defect due to genetic mutations of the LDL receptor gene is the cause of familial hypercholesterolemia (F. H.), a disease characterized by high cholesterol levels and premature atherosclerosis. Injection of autologous radiolabelled LDL, followed by hepatic scintiscanning, can be used to obtain "in vivo" quantification of hepatic receptor activity, both in normal and hypercholesterolemic patients. In this study we observed no hepatic increase of radioactivity in patients affected by F. H., confirming the liver receptor defect. Scintigraphy is a non-invasive technique which can be used to diagnose this disease and to monitor the efficacy of hypolipidemic therapy. PMID- 1926874 TI - [Early rehabilitation measures in the area of urologic excretion]. AB - Among 126 patients in neurorehabilitation, most of them suffering from cerebral vascular disease, 78 were afflicted by a disturbance of urinary excretion, which could be alleviated in 42 cases (54%) during the first 3 weeks of therapy. In more than half of catheterized patients the catheter could eventually be abandoned. In terms of our rehabilitation scale, we could observe an improvement of 53% in scale points during the period of treatment. We adhere to a scheme of consistent cooperation between urologists and neurologists with respect to optimal and economical care for the catheterized patient with regular training of the vesical sphincter. Rational medication can in some cases take advantage of side-effects of drugs which are indicated for the primary disorder anyway. Permanent communication between the medical specialist in rehabilitation, the neurologist and the nurse is an essential requirement. Psychological and environmental aspects have to be considered in order to treat the patient as a complex entity. PMID- 1926875 TI - [Prerequisites and guidelines for acclimatization to great and extreme altitude in prevention of altitude sickness]. AB - Acute mountain sickness is a possible danger of life but it appears in fact absolutely not as fateful or unavoidable because it's evidence occurs as the consequence of missed observation of the specific conditions as much as of individual misbehaviour to altitude. Before someone plans to travel or climb at high altitudes by sharing a trekking-tour or an expedition-team medical advices for prevention of severe incidences caused by the reduced oxygen at altitudes are of utmost importance. Thereby it is not the question of the individual suitability to altitude which appears in the foreground but the need to find out typical health restrictions and, first of all, to develop an individual concept of optimal acclimatization to altitude. In this synopsis therefore all relevant aspects of preparation, precautions and detailed methods of acclimatization to altitude are laid down corresponding to the actual knowledge of altitude medicine and will be presented as crucial guiding principles for trekking and climbing to high altitudes. PMID- 1926876 TI - [The contribution of modern biology to a better understanding of disease]. AB - The human disease in its biological foundation must be congruent with the normal processes of the life and explicable by these. The simplified view on disease in the past with the reduction on its biological and physico-chemical course seems to become more and more insufficient and limiting to a comprehensive understanding. The discussion of the concept of disease from the standpoint of the epistomology needs in consequence of the so called new thinking the integrated inclusion of the systems theory, the theory of chaos and the concept of layers by Riedl. Taking this in the consideration a comprehensive understanding of disease is given. This allows to take into account as well its evolutionary conditionality, its human being as its individual, group, population and species specific characteristics. This kind of view emphasizes the necessity to complete the pragmatic reductionism by a comprehensive sight. In the consequence of such a thinking it seems easier to recognize the with the increasing complexity of the living beings emergent laws. PMID- 1926877 TI - [Joseph Weiger and the introduction of anesthesia in Vienna]. AB - The first administration of ether in Vienna was performed by Schuh in 1847. 2 days later also von Wattmann used ether for anaesthesia. Approximately at the same time the nowadays nearly unknown dentist Joseph Weiger began to give ether anaesthesia for dental surgery. He reported in 1850 about his experiences in more than 21,000 operations. A further publication in 1851 gave a survey about the known ether literature. PMID- 1926878 TI - [The treatment of metastasizing breast carcinoma using antiestrogens]. AB - Results of adjuvant hormone therapy with Tamoxifen, an antioestrogenic substance, have been discussed. 82 patients in 2 groups who were diagnosed with metastatic mammary carcinoma received Tamoxifen (ICI) and Tamoxifen (Ebewe) orally in a dosage of 20 to 40 mg/day. 43% of the patients in group A (Tamoxifen, ICI) experienced complete or partial remission of the metastases. In group B (Tamoxifen, Ebewe), this result was achieved in 54% of cases. The better results were due to the fact that the disease was not so advanced in the group B patients and they were also longer in the menopause. Thus in terms of efficacy, the preparations are identical. Severe side effects due to the therapy were not observed. PMID- 1926879 TI - [Effects and side effects of intravenous gamma globulin I: the problem of immune complex formation]. AB - This is an original contribution to the side effects of i.v. gamma globulin in patients with immunodeficiency. 73 therapies were carried out, 9 patients suffered from partially life-threatening complications. All side effects were fully reversible and occurred during the transition from antigenaemia to antibody excess. Immunecomplexes could be quantified and C4 decreased. In view of these results we have modified our protocol giving 5 S prior to 7 S. No further complication was seen in the following 148 therapies. Hence we can conclude, that at least some complications of the i.v. gamma globulin-therapy is due to the formation of immunecomplexes and can be prevented by the application of 5 S prior to 7 S. PMID- 1926880 TI - [Physical medicine--a field between empiricism and science]. AB - Physical Medicine is more deeply rooted in empiricism than most other medical fields. This causes problems and the demand for scientific testing of its methods. Selected examples are given relating to prevention, therapy and rehabilitation. They show that scientific testing is possible also in Physical Medicine and can lead to positive results. PMID- 1926881 TI - [The expertise situation as pathoplastic factor]. AB - Underlying attitudes of apprehension or desire have an essential pathoplastic function, especially in the situation of medical assessment. The functionality of symptoms and complaints requires a diagnostic approach which is not oriented simply towards the "exclusion of organic causes". Interaction between somatogenic and psychogenic factors is by far more common than sheer functionality. Although widely neglected in our medical teaching and literature, these problems are not confined to the mere assessment of temporary or permanent invalidity, but are of great importance for the entire medical sphere, including manifestations and course of a disease, therapeutic success etc. In Austria, the population of foreign workers is in a special position due to socio-economic preconditions, partly due to short-sighted policy devoid of psycho-hygienic considerations. This situation requires thorough analysis free of emotions, which should lead to the development of sensible, although in some respects belated, measures. The latest economical recession has revealed several faulty courses of development in our system of social and health insurance, which needs revision urgently lest it should collapse. In this respect, the medical profession is called upon to contribute to a necessary curtailment of excessive misuse within a system that has become inflexible during the past decades, thereby endangering the valuable achievements of social medicine. PMID- 1926882 TI - [The physician as judicial expert witness]. AB - Excellent special knowledge and consideration of the limits of competence in his own special field as well as in the court procedures are characteristic of a medical expert at law court. Only he provides medical expert knowledge that the court lacks in criminal, civil and social law. This must not mislead him to try to solve legal problems, ie to play the role of a "judge in white". Therefore knowledge of our jurisdiction is a necessity. Duties and rights of medical experts are discussed. The necessary human conduct with the person concerned is emphasized. The correct way of preparing an expert evidence is discussed in the special case of the causal connection. In conclusion it seems mandatory to include the topic 'medical expert' into the theoretical and practical education of physicians. PMID- 1926883 TI - [Seizures and driver's licence]. AB - Legislation leaves a wide margin of freedom of judgement to the medical expert in the forensic assessment of a person's suitability for holding a driver's license. We have to make use of this freedom very cautiously with regard to social aspects as well as to the presently accepted state of scientific knowledge. In cases of first manifestations of epilepsy we must postulate--as a rule of thumb--a seizure free period of two years with regular medication and clinical and electro encephalographic checkups. The (epileptic or non-epileptic) "accidental seizure" is characterized by the releasing influence of powerful external noxious factors. In these cases, the patients should be seizure-free for at least six months before driving can be resumed. In all cases, the evaluation depends on the continuous observance of the patients, taking into account any underlying primary illness (alcoholism, cerebral vascular disease, conditions following brain surgery or trauma). The organic brain syndrome is an essential additional factor, together with the feasibility of treatment and the patient's compliance. Evaluation of the clinical picture is of foremost importance, support by EEG findings, serum levels and psychological tests. Knowledge of cumulative factors, elimination and side-effects of anticonvulsive drugs is essential. According to the present view, medication should be continued over a period of many years. Curative medicine and medical assessment are not mutually exclusive, but require a distinct differentiation in every single case. PMID- 1926884 TI - Recurrence of 131I-induced thyroid storm after discontinuing glucocorticoid therapy. AB - A 19-year-old woman with Graves' disease developed thyroid storm 8 days after radioactive iodine therapy. The clinical manifestations of thyroid storm promptly improved after treatment with large doses of propylthiouracil, potassium iodide, propranolol hydrochloride, and dexamethasone. Four days after discontinuing dexamethasone, the syndrome recurred and was corrected by reinstitution of the glucocorticoid. We conclude that dexamethasone was an important adjunct for treating thyroid storm and was effective mainly by reducing peripheral triiodothyronine production. PMID- 1926885 TI - Pyomyositis secondary to group A beta hemolytic streptococcus. AB - Pyomyositis is a primary bacterial infection of skeletal muscle not formed by local extension from superficial tissues. It is relatively frequently seen in tropical climates but reportedly rarely seen in temperate climates such as North America. In this report, we present a 67-year-old man with a primary Group A beta hemolytic Streptococcal infection of the quadriceps muscle of the left leg. PMID- 1926886 TI - Effect of a sensitive thyrotropin-stimulating hormone assay on dosing of L thyroxine. AB - The Wisconsin Veterans Home has had a special interest in thyroid disease since 1986. Until recently, dosage adjustment of L-thyroxine in residents with primary hypothyroidism was accomplished by individual physicians guided by standard thyroid function tests. A shift to a sensitive thyrotropin-stimulating hormone (TSH) assay provided an opportunity to assess the frequency of sensitive TSH suppression secondary to excessive doses of L-thyroxine which would not be recognized by the standard TSH assay. We reviewed the charts of 46 residents who were not acutely ill and had been in the facility at least 6 months. Sensitive TSH was determined while on a stable dose of L-thyroxine for a minimum of 6 weeks. Six residents (13%) had low sensitive TSH levels indicating an excessive dose of L-thyroxine. The application of the sensitive TSH assay resulted in dose reduction. PMID- 1926887 TI - Topical diphenhydramine toxicity. AB - This paper will review an acute onset of mental confusion associated with hallucinations secondary to vigorous administration of topical Caladryl lotion and Benadryl spray in an 8-year-old boy with chickenpox. The article discusses the toxicity of both oral and topical diphenhydramine use, along with the differentiation of varicella encephalitis from diphenhydramine toxicity. Delirium can be described as an acute clouding of consciousness associated with visual and tactile hallucinations, disorientation, and misperceptions. In a child who is already suffering from an infectious illness, encephalitis must be high on the list of the physician's differential diagnosis. The physician, however, must never overlook ingestions, even from topical, over-the-counter medications. The case described illustrates this point. Although this appears to be the fourth case report on this subject, the diagnosis was partially obscured by the fact that the local pharmacist could not find any documented cases despite a computer search of diphenhydramine toxicity at the time of admission and the report of only one or two cases by the Parke-Davis pharmacist. PMID- 1926888 TI - The Wisconsin Area Health Education Center System. PMID- 1926889 TI - Malignant mesothelioma in Wisconsin, 1959-1989. PMID- 1926890 TI - Wisconsin doctor selected as national symbol of physicians' sacrifices. PMID- 1926891 TI - SMS president speaks out against AIDS hysteria. PMID- 1926892 TI - Demonstration projects for the integrated prevention and control of noncommunicable diseases (INTERHEALTH programme): epidemiological background and rationale. INTERHEALTH Sterring Committee. AB - Noncommunicable diseases--cardiovascular and cerebrovascular disease, pulmonary diseases, liver disease, cancer, diabetes, osteoporosis and trauma--constitute the major cause of death in developed countries and are predictably emerging as significant threats to health in countries at intermediate stages of the epidemiological transition. Based on the philosophy that diseases with common risk factors (inadequate prevention/control services, smoking, fat/salt diet, alcohol use, etc.) require common preventive strategies, the INTERHEALTH demonstration projects are designed to build regional capacities and to exchange social and medical technologies for broad-gauged noncommunicable disease prevention and control. Projects are at various stages of planning and implementation in all WHO regions: Africa (Mauritius, United Republic of Tanzania); the Americas (Chile, Cuba, United States); Eastern Mediterranean (Cyprus); Europe (Finland, Malta, USSR); South-East Asia (Sri Lanka, Thailand); the Western Pacific (Australia, China, Fiji, Japan). This article presents selected data which illustrate the long-term mortality trends and present noncommunicable disease risk-factor levels in participating countries at different stages of the epidemiological transition. The shift towards noncommunicable diseases as a cause of death is readily apparent and combinations of risk factors are present in each of the populations studied in the baseline phase of this research and demonstration programme. The use of data to estimate the noncommunicable disease-related mortality burden from different lifestyles and risk factors is illustrated and findings from the most advanced demonstration studies are briefly outlined. PMID- 1926893 TI - The lifestyle concept and health education with young people. Results from a WHO international survey. AB - This article draws upon data from a unique, 11-country study of young people's health behaviour, facilitated by the WHO Regional Office for Europe. Analyses of the data available on individual health behaviours cluster into two groups: (i) health enhancing behaviours; and (ii) health-compromising behaviours. The results were analysed to identify the strength and consistency of these lifestyles across countries. A relatively modest proportion of the variance of the original variables was explained by these two lifestyle factors, but a consistent pattern emerged between countries. This consistency indicates that the health-related lifestyles of young people may not vary greatly between the countries in the study, a finding which might be used as an encouragement for greater international cooperation in the development and use of health education materials for young people, which may be easily transferable between countries. The data also support a more integrated approach to health education based on the promotion of healthy lifestyles, rather than a focus on individual health behaviours. PMID- 1926894 TI - Urbanization and health in developing countries. AB - In developing countries the level of urbanization is expected to increase to 39.5% by the end of this century and to 56.9% by 2025. The number of people living in slums and shanty towns represent about one-third of the people living in cities in developing countries. This article focuses upon these poor urban populations and comments upon their lifestyle and their exposure to hazardous environmental conditions which are associated with particular patterns of morbidity and mortality. The concept of marginality has been used to describe the lifestyle of the urban poor in developing countries. This concept is critically examined and it is argued that any concept of the urban poor in developing countries being socially, economically or politically marginal is a myth. However, it can certainly be claimed that in health terms the urban poor are marginal as demonstrated by some of the studies reviewed in this article. Most studies of the health of the urban poor in developing countries concentrate on the environmental conditions in which they live. The environmental conditions of the urban poor are one of the main hazards of the lifestyle of poor urban residents. However, other aspects of their way of life, or lifestyle, have implications for their health. Issues such as smoking, diet, alcohol and drug abuse, and exposure to occupational hazards, have received much less attention in the literature and there is an urgent need for more research in these areas. PMID- 1926895 TI - A cross-cultural pilot study on alcohol education and young people. AB - Alcohol use has become normative for adolescents in most developed and developing countries, with serious health implications. In response to this problem, the World Health Organization convened a group of investigators in 1985 from centres in four countries--Australia, Chile, Norway and Swaziland--to participate in a pilot study on the efficacy of the social influences approach in school-based alcohol education. The goal of the educational programme was to delay onset and minimize involvement of alcohol use among 13-14 year-old adolescents. 25 schools in the 4 countries, representing middle- and lower-class populations, were randomly assigned to peer-led education, teacher-led education or a control condition. The programme focused on the social and environmental influences to drink alcohol, and skills to resist those influences. It consisted of 5 lessons over 2 months. Baseline and post-test data measured alcohol-use knowledge, attitudes, skills and friends' drinking patterns. Data were collected immediately prior to and 2 months following the educational programme. The data converge on the finding that peer-led education appears to be efficacious in reducing alcohol use across a variety of settings and cultures. PMID- 1926896 TI - [Life style and prevention of cerebrovascular accidents]. AB - Cerebrovascular diseases (CVD) claim 1.5 million lives each year in industrialized countries; in developing countries, estimates suggest the same distressing trends. CVD rank as the third leading cause of death after ischaemic heart disease and cancer. Surviving patients are left disabled and paralysed, dependent on their families and on society. Lifestyle, an issue of concern both for the individual and the community, can play an important role in the primary prevention of CVD when combined with dietary adjustments and appropriate drug therapy; it can prevent and slow down the development of atheroma, help to regulate blood pressure and contribute to the prevention of heart diseases likely to cause embolic strokes. The preventive treatment and management of other conditions, such as rheumatic heart disease, coronary artery disease with myocardial infarction and cardiac arrhythmias (embolic strokes), combined with healthy eating habits that tend to reduce the intake of saturated fats (atherosclerosis) and salt (high blood pressure) and the avoidance of smoking and alcohol (ischaemic and haemorrhagic strokes) will help to lower the incidence of mortality and morbidity due to CVD. PMID- 1926898 TI - The medium is not the message. PMID- 1926897 TI - [Tobacco use in Spanish women]. AB - Tobacco consumption among Spanish women has increased dramatically during the last 40 years, rapidly closing the gap between men and women in cigarette-smoking prevalence. This has already happened in the younger age group, in which the proportion of young women smoking is reaching that of young men. This pattern has been evidenced in several surveys carried out at the regional and country levels. The younger generation of Spanish women, together with its counterparts in France and the Netherlands, has one of the highest prevalences of tobacco consumption (49%) in the EEC, considerably higher than the corresponding average for the EEC as a whole (39%). In Spain, a female smoker tends to be young, educated and in the upper-income level. Applying the standard attributable-risk approach, it has been estimated that in 1986 approximately 8,000 female deaths resulted from cigarette smoking in Spain, representing about 6% of all female deaths, with the majority being due to diseases of the circulatory system. Between 1980 and 1987, female hospital admissions due to lung cancer increased more than a 100%. In forthcoming years in Spain, one can expect a dramatic increase in the absolute number of female deaths caused by smoking-related diseases, due to the increase in smokers among the young generations, who will eventually attain the ages at which smoking-related disease appear. This younger age group is comparable to male smokers, and as they move into their 60s and 70s, their risk of lung cancer and ischaemic heart disease will most likely come to resemble the risks for men smoking the same numbers of cigarettes today.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1926900 TI - Evaluation of an imipenem/cilastatin target drug program. AB - This article describes an imipenem/cilastatin (I/C) target drug program. The program, developed following completion of a drug usage evaluation study, was designed to improve I/C dosing, reduce central nervous system (CNS) adverse effects, and reduce antibiotic costs. Following completion of an inservice education program for the medical and pharmacy professional staffs, ongoing monitoring of I/C usage was accomplished through the pharmacy-based drug-dosing service. Pharmacists evaluated I/C dosage based upon culture/sensitivity results and indicators of renal function. If deemed inappropriate, the pharmacist contacted the prescribing physician with a dosage recommendation. Two hundred ten courses of I/C therapy were prescribed in the nine-month period following implementation of the target drug program; 26 cases (12 percent) required dosage adjustment. The incidence of CNS adverse effects including seizures decreased from 15 to 1 percent (p = 0.0015). A $6033 drug cost avoidance also resulted from pharmacist intervention. PMID- 1926899 TI - Ceftizoxime disposition in neonates and infants during the first six months of life. AB - The single-dose pharmacokinetics of ceftizoxime sodium were studied in 52 neonates and infants between 0.1 and 189 days of age. Subjects received ceftizoxime 25 or 50 mg/kg iv over 15-30 minutes. The drug was administered q8 12h for five days to permit tolerance evaluation on repetitive dosing. No differences were observed in ceftizoxime pharmacokinetic parameter estimates relative to dose. However, marked differences were observed in ceftizoxime pharmacokinetic characteristics relative to infant age; ceftizoxime half-life and mean residence time decreased, whereas body clearance increased with infant age. Ceftizoxime volume of distribution remained relatively constant over infant age. No adverse effects associated with ceftizoxime administration were observed. These data suggest that ceftizoxime 50 mg/kg q12h be used for infants less than or equal to 2 weeks of age (less than or equal to 40 weeks postconceptional age) and that 50 mg/kg q8h be administered for older infants. PMID- 1926901 TI - Seizure activity associated with imipenem use: clinical case reports and review of the literature. AB - Two patients with multiple organ systems failure developed seizures after receiving imipenem/cilastatin (I/C) despite dose adjustment for poor renal function. Neither patient had a past history of seizures, nor had experienced seizures after receiving high doses of other beta-lactam antibiotics. Simple dose adjustment of I/C based on low creatinine clearances may not be adequate to prevent seizures. PMID- 1926902 TI - Impaired water homeostasis following mixed carbamazepine and phenobarbital overdose. AB - Both carbamazepine and phenobarbital are known to have antidiuretic properties when administered chronically. We describe a case of acute impairment of body water homeostasis following mixed drug overdose with carbamazepine and phenobarbital. Serum carbamazepine concentrations correlated with alternating states of diuresis and antidiuresis. We recommend close monitoring of fluid and electrolyte status in carbamazepine overdose. PMID- 1926903 TI - In vivo inactivation of tobramycin by piperacillin. AB - In vivo inactivation of aminoglycosides by antipseudomonal penicillins in patients with renal failure can be a significant problem when these drugs are used together in certain gram-negative infections. Our article illustrates the possible magnitude of this interaction and the resultant effect on aminoglycoside pharmacokinetic parameters. Penicillin concentrations remain relatively unaffected by this interaction. This article stresses the need for close monitoring of aminoglycoside concentrations when combined with antipseudomonal penicillins in this patient population. PMID- 1926904 TI - Effect of I-Scrub on signs and symptoms of chronic blepharitis. AB - To assess the effect of I-Scrub (Spectra Pharmaceutical Services), a new detergent eyelid scrub, on the subjective symptoms and objective clinical signs of chronic blepharitis, 20 patients with this disease were treated for three weeks. None of them yielded positive cultures for virulent bacteria from the eyelids and conjunctiva. Most of the patients reported significant reduction in the subjective symptoms and in the severity of the clinical signs as well. No adverse effects were observed. The results of our study suggest that this product is of value as a detergent eyelid scrub in the treatment of chronic blepharitis. PMID- 1926905 TI - Verapamil in premenstrual syndrome. PMID- 1926906 TI - Vitamin E as an anticonvulsant. PMID- 1926907 TI - Alprostadil in impotence. PMID- 1926908 TI - Pravastatin sodium, a new HMG-CoA reductase inhibitor. AB - The rate-limiting step in cholesterol biosynthesis is controlled by the enzyme 3 hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Inhibitors of this enzyme lower serum cholesterol very efficiently by increasing cellular uptake of cholesterol-rich, low-density lipoproteins. Pravastatin, a derivative of mevastatin and in the same class as lovastatin, lowers total cholesterol concentrations by 20-30 percent in patients with hypercholesterolemia. In patients who also have hypertriglyceridemia, serum triglyceride levels are decreased. Detailed pharmacokinetic data and long-term adverse-effect experience with pravastatin are extremely limited. The issue of tissue-selectivity for pravastatin has given rise to the marketing terminology "second-generation" HMG CoA reductase inhibitor, but any clinical advantage of pravastatin over other HMG CoA reductase inhibitors remains to be demonstrated. PMID- 1926909 TI - Ketoconazole in the treatment of pityriasis versicolor: international review of clinical trials. AB - Multiple open and double-blind studies have confirmed the efficacy of ketoconazole in the treatment of pityriasis versicolor. Single-dose (400 mg) or short-course (200 mg/d for five days) therapy may be highly effective for selected patients with pityriasis versicolor. Toxicity seems to be minimal at this dosage. PMID- 1926910 TI - Is heparin really necessary in the lock and, if so, how much? AB - The literature on the issue of whether heparin is necessary in an intermittent peripheral venous access device (lock) is critically reviewed. Issues explored include loss of patency, development of phlebitis, duration of lock placement, type of cannula material, sample size, risk of toxicity with heparin flush solutions, risk of clot embolism, and physical or chemical incompatibilities. Available studies indicate that heparin is not necessary to maintain fluoroethylenepropylene (FEP-Teflon) peripheral venous access devices unless the lock is used to obtain blood specimens. Considering the benefit-to-risk ratio for the use of heparin, it is advisable to maintain FEP-Teflon locks with normal saline alone. When locks are used to obtain blood specimens, as in a pharmacokinetic study, then a dilute heparin flush solution should be used. Whether heparin is necessary for the maintenance of locks composed of other materials is uncertain. Newer, less thrombogenic materials such as ethylene tetrafluoroethylene may also obviate the need for heparin, but comparative trials in a larger number of patients are needed for confirmation. When heparin is used, an effort should be made to avoid systemic toxicities by using the lowest known effective concentration (10 units/mL) pending further studies. PMID- 1926911 TI - Prostaglandin E1 treatment of congenital heart disease: use prior to neonatal transport. AB - Prostaglandin E1 (PGE1) is used to maintain the patency of the ductus arteriosus in neonates when it is necessary to circumvent a defect in the heart or aorta in order to provide adequate peripheral perfusion. It has recently been recommended that medical stabilization with PGE1 be done as soon as a ductus-dependent cardiac defect is suspected, preferably prior to transport of the infant to a tertiary care center for surgical repair of the defect. To accomplish this, hospitals providing obstetric services will need to maintain a supply of PGE1. This commentary provides guidelines for determining the need to stock PGE1 and presents a brief review of the physiology of the ductus arteriosus and the pharmacology and adverse effects of PGE1 therapy. PMID- 1926912 TI - Perceived purpose of prescription drugs: the Iowa 65+ Rural Health Study. AB - In order to assess elderly patients' knowledge of their medications, the Iowa 65+ Rural Health Study asked a rural, elderly population the purpose of their prescription drugs. Ten percent of all drug purposes reported were considered inappropriate by our criteria. There was some variability between therapeutic categories and their frequency of purpose misperception. For 40 percent of drugs whose purpose was inappropriate, the respondent reported another drug for which that purpose would have been appropriate. Respondents were as likely to state a medication's appropriate purpose whether it had been dispensed by a pharmacy or a physician. The highest percentage of drugs whose purpose was appropriately perceived was dispensed by mail-order pharmacies. PMID- 1926913 TI - The relationship between outpatient drug costs and disease progression in the human immunodeficiency virus-infected population. The Military Medical Consortium for Applied Retroviral Research. AB - As the focus of the management of human immunodeficiency virus (HIV) infection turns from the treatment of AIDS to the entire continuum of the disease, projection of long-term healthcare costs becomes increasingly important. Rather than a fulminant disease treated primarily inside the hospital, HIV infection will become a chronic condition requiring years of outpatient monitoring and pharmacologic intervention with attending increases in pharmacy costs. The objective of this study was to characterize outpatient drug costs by Walter Reed (WR) disease stage in order to estimate the association of disease progression and outpatient prescription drug costs. We hypothesized that there was an association between HIV disease progression, measured by the WR Staging Classification System, and outpatient prescription drug costs. Outpatient drug costs were summarized for 190 HIV-positive patients during a three-month period who presented at Walter Reed Army Medical Center for staging and follow-up. The overall median cost per day per patient for all stages was $3.21 (range $0.01 53.45) with wide variation between patients. Daily costs for patients in WR stage V were the greatest (median $9.26). There was a significant association between WR stage of disease and outpatient drug costs (Spearman rho = 0.51, t = 6.9, df = 188, p less than 0.001). The association was not completely linear because costs in WR stage VI were less than WR stages IV or V. Annual extrapolated outpatient drug costs for these 190 patients would be nearly $0.5 million. PMID- 1926914 TI - Use of estrogens among middle-aged Massachusetts women. AB - This study describes estrogen use among 45- to 55-year-old white women in Massachusetts from 1981 to 1987. In a 1981 cross-sectional survey, 7705 white women (77 percent response rate) returned a questionnaire or were interviewed by phone. Premenopausal women were invited into a 4.5-year follow-up study including telephone interviews every nine months, and 2236 (approximately 91 percent of the eligible women) had a complete follow-up. In the cross-sectional survey, 7.9 percent had used oral estrogens in the last two weeks, but most (77 percent) had had a hysterectomy; use varied notably from one area to another. Vaginal estrogens were used by 2.9 percent. Users and nonusers of oral estrogens were quite similar in regard to sociodemographic background. Data from the follow-up surveys showed that estrogen use increased throughout the study period and by the final follow-up women with higher education status reported more estrogen use than those with lower education status. Most women used estrogens only for a short time. PMID- 1926916 TI - Rho Chi Lecture. Ideals and innovation: drugs, generics, the FDA, and the pharmacist. PMID- 1926915 TI - Emergency healthcare in India. PMID- 1926918 TI - Fluoxetine and glaucoma. PMID- 1926917 TI - Pharmacists and the mandate of pharmaceutical care. AB - Implementing the mandate for delivery of drug therapy to achieve definite outcomes that improve a patient's quality of life is discussed from the perspective of the changes currently needed in both practice and education. Specifically, changes in practice should include: (1) a managerial framework that continuously supports clinical activities in everyday practice, (2) recognition of competence in clinical practice, and (3) documentation of and reimbursement for clinical service. Changes in education should include: (1) teaching of problem-solving skills to students by faculty/practitioners, and (2) redirecting the curricular content to provide the minimum knowledge base required for competent clinical practice. Pharmacists will begin to accept the mandate of pharmaceutical care when there is widespread training and use of technicians, implementation of problem-based education in the schools, and adequate problem solving support for pharmacists in practice. PMID- 1926919 TI - Possible procainamide-induced myopathy. PMID- 1926920 TI - Inadvertent intravenous administration of methylprednisolone acetate in a child. PMID- 1926921 TI - Volmax: simulated gastrointestinal pH and agitation studies. PMID- 1926922 TI - Comment: potassium supplements vs. potassium-sparing diuretics. PMID- 1926923 TI - [Current concepts of diagnosis and therapy of myocarditis from the clinico immunologic viewpoint]. PMID- 1926924 TI - [Follow-up of patients with histologically confirmed myocarditis]. PMID- 1926925 TI - [Detailed echocardiography findings in follow-up of inflammatory myocardial diseases]. PMID- 1926926 TI - [Differential diagnostic problems of chronic myocarditis from the pathomorphologic viewpoint]. PMID- 1926927 TI - [Therapy and rehabilitation of patients with myocarditis]. PMID- 1926928 TI - [Ineffectiveness of serial x-ray examinations in control of lung cancer--results of epidemiologic studies]. PMID- 1926929 TI - [The 150th birthday of the anatomist August Rauber (1841-1917)]. PMID- 1926930 TI - [Differential indications for heart medications]. PMID- 1926931 TI - [The metabolic syndrome]. PMID- 1926932 TI - [Family status and hypertension]. PMID- 1926933 TI - [Splenic rupture in infectious mononucleosis]. PMID- 1926934 TI - [The relationship between smoking and angina pectoris]. PMID- 1926935 TI - [The combined application of ultrasound and impulse current]. PMID- 1926936 TI - [Paroxysmal positional dizziness as postoperative complication]. PMID- 1926937 TI - [Population-related study of the prevalence of various gynecological operations and of the incidence of malignant gynecological tumors before the age of 55]. PMID- 1926938 TI - [Nosocomial infections in autopsy material in surgically treated patients]. PMID- 1926939 TI - [Wholeness and diversity--their reflection in medical science]. PMID- 1926940 TI - [150th birthday of Max Jaffe]. PMID- 1926941 TI - [The potentials of erythromycin derivatives in the treatment of gastrointestinal motility disorders]. AB - In low dosages erythromycin imitates the effect of motilin on the gastrointestinal motility. In vitro experiments show that erythromycin is a motilin agonist: it displaces motilin which is bound to its receptor; it directly acts on smooth musculature and it possesses the same animal and tissue specificity. Structural changes cause adequate changes in the binding affinity and in the contractile activity. Several motilides such as erythromycin derivatives with prokinetic properties have no antibiotic activity, but they cause a distinct increase of the prokinetic activity. Motilides may be defined as a new group of prokinetic substances: the motilinomimetics. Erythromycin normalises the delayed evacuation of the stomach of solid and fluid food in diabetic, idiopathic and postvagotomy gastroparesis. For the treatment of gastrooesophageal reflux disease, gastritis, pathological overgrowth of the small intestine, hypokinesia of the gallbladder and the chronic obstipation erythromycin appears as a promising medicament. The substances with a stronger effect may become even still more useful medicaments. A better understanding of the relation between motilin and motilides may lead to new knowledge about the regulation of the gastrointestinal motility. PMID- 1926942 TI - [Generalized tendomyopathy (fibromyalgia)]. AB - The generalised tendomyopathy (fibromyalgia) is one of the most frequent rheumatological diseases and has a prevalence of approximately 1%. Multilocular conditions of pain of the back, the extremities and the face with increased tenderness on pressure on defined insertions and courses of the tendons clinically stand to the fore. Functional disturbances, vegetative symptoms and psychopathologic changes are frequently connected with this. Laboratory investigations are normal. The diagnosis results from the combination of multilocular conditions of pain - combined with the defined tenderness on pressure mentioned and as additional symptoms functional disturbances, vegetative symptoms and psychopathological changes. In the genesis of the disease probably reflex mechanisms on the part of the spinal column, partly also on the peripheral joints primarily play a role. Probably the generalisation is evoked above all by psychosocial factors which possibly cause the various symptoms by a continuous impulse on the reticular formation. PMID- 1926943 TI - [Generalized tendomyopathy (fibromyalgia): differential diagnosis, therapy and prognosis]. AB - The generalised tendomyopathy is one of the most variegated and fascinating disease of man. The unusual constellation and combination of symptoms constrain to the differential-diagnostic demarcation of a great number of rheumatic and non rheumatic diseases. While the rheumatic polymyalgia and myositis are easily to be demarcated, the decision between a primary and secondary generalised tendomyopathy can be difficult. In individual cases a classical tendomyopathy can be accompanied by antinuclear factors and then it is at the earliest a "collagenosis the state of waiting". The therapy of tendomyopathy is altogether unsatisfactory. All forms of therapy (medicamentous, physical, psychotherapy) help at the utmost in 50%. Surprisingly, on the part of the medicaments the non steroidal antiphlogistic drugs and the glucocorticoids in most cases completely fail, and also the physical therapy is frequently not tolerated and/or has only a short duration of effect. The more important are the influence on possible evoking factors, the optimization of the social background and the utilization of the possibilities of the "secondary prevention" (balneotherapy in a health resort, sauna bath, Kneipp's applications, change of the living and working conditions, easy sports activities). Since the disease is frequent, but not yet known in general, it should be made better acquainted among the physicians. The generalised tendomyopathy is and remains a cardinal problem not only of rheumatology, but of the physician's working-day in general. PMID- 1926944 TI - [Paget-von Schroetter syndrome: case description in the light of the literature]. AB - A 27 year old patient with a thrombosis of the subclavian vein (Paget- von Schroetter's-syndrome) was treated successfully with a systemic streptokinase thrombolysis. Indications and success of the different therapeutic ways in current literature (conventional management, systemic and local thrombolysis) are compared to each other. The authors prefer treatment with systemic thrombolysis, patients with contraindications should be treated with conservative management. Nevertheless no final conclusions can be drawn, as there are no controlled studies comparing the different concepts in treatment. PMID- 1926945 TI - [Ventricle-vessels relationship in aspects of hypertension]. AB - The diagnostics of the ventricle-vessel relations in arterial hypertension is significant in particular for advanced stages. Under the aspect to regard the cardiac contraction in form of a model as temporarily varying elastance of the volume invasively (P-measurement, V-measurement, preload alteration via balloon in the inferior vena cava) relations of the ventricular pressure volume (ESPVR, EDPVR) and system-arterial ones in form of the effective arterial elastance can be established. Additionally calculated functional curves give separated information concerning the influence of preload, afterload and contractility on the stroke work. Thus a comprehensive statement concerning the cardiovascular function and a basis for valuable therapeutic effects is worked out. Several references result for advanced stages of the arterial hypertension with hypertrophied heart. The systolic function remains normal for a long time. Diastolically the increasingly disturbed relaxation with pathological preload is found. The relation stroke work-afterload is no more in the optimum region and can further be deteriorated by vasodilation. Whether or not, however, this relation has the same relevance for all clinical questions, remains open. Is the stroke work really that parameter which shall be optimized therapeutically? PMID- 1926946 TI - [Comparative studies of in-vivo and in-vitro contraction behavior of gallbladders with impaired function]. AB - The contractility of human gallbladders without calculi of 10 patients with typical biliary pain was investigated in vivo (n = 7; pharmacosonography) and in vitro (n = 10; isometric registration). In 6 out of 7 cases, investigated in vivo as well as in vitro, the contractility was identical--therefore the smooth-muscle preparation in the organ-bath could be an interesting model for studies with CCK antagonists. 3 of the in-vitro-preparations showed hypomotility consecutive to acetylcholine- and CCK-stimulation. Histologically, the destruction of the normal gallbladder wall structure by scars, chronic inflammation and the evidence of so called Rokitansky-Aschoff-sinuses could be proved. The importance of these findings probably causal to the process of cholelithogenesis is discussed. PMID- 1926947 TI - [The instrumental diagnosis of arterial diseases especially of arterial occlusive diseases]. AB - Ultrasound Doppler sonography is the most important tool in the assessment of peripheral arterial occlusive disease. The determination of systolic ankle pressure gives an useful overview of the degree of the disease. In a normotensive patient with a systolic blood pressure of 140 mm Hg systolic ankle pressures between 100 and 140 mm Hg are present when the occlusive disease is in the stage of good compensation. Severe claudication will appear with ankle pressures between 70 and 95 mm Hg, lower values are indicating a critical limb ischaemia. Treadmill exercise is helpful for documentation of painfree and maximal walking distances. When a patient is suggested to be treated by percutaneous transluminal angioplasty or bypass surgery a duplex sonography or angiography is mandatory. In evaluating the Raynaud's phenomenon under the noninvasive techniques capillaroscopy of the nailfold is a useful tool. The diagnosis of thromboangiitis obliterans is usually established by clinical criterias. The radiographic findings may give important hints. In many cases of acute arterial occlusions angiography is necessary for finding the optimal therapy. The aneurysm of the abdominal aorta will be evaluated by ultrasound and computer tomography. PMID- 1926948 TI - [Tuberculosis treatment today]. AB - In West and East Germany the incidence of tuberculosis is declining. However, with an incidence of 22 per 100,000 inhabitants in West Germany and 17 new diseases per 100,000 inhabitants in East Germany it is not a rare disease. In the chemotherapy of pulmonary tuberculosis, isoniazid (INH), rifampicin (RMP), ethambutol (EMB), streptomycin (SM), pyrazinamide (PZA) and prothionamide (PTH) are the most relevant drugs. The chemotherapy of tuberculosis is always carried out as a combination therapy of at least three drugs. A rapid cultural conversion of the sputum as well as low rates of failures and relapses are regarded as parameters of quality. Therefore six-month-regimens with initially four drugs (INH + RMP + PZA + SM or EMB) or nine-(twelve-) month-regimens with initially three medicaments (INH + RMP + PZA, or INH + RMP + EMB or INH + RMP + SM) may be recommended. Peculiarities of the therapy in patients with AIDS, with drug resistance, with relapses. PMID- 1926949 TI - [A viatorium medico-historicum. V. Places of memory in southern and northern districts of Saxony-Anhalt]. AB - The fifth part of the treatise on a viatorium medico-historicum directed on the region of Saxony-Anhalt leads through the southern and northern districts of this country. Important points of the history of medicine, pharmacy and the natural sciences are nominated. Life and work of personalities who were born in this region or worked there are briefly described. PMID- 1926950 TI - [Lease agreements of physicians' practices--what should be considered?]. PMID- 1926951 TI - [Psyche and gastrointestinal diseases: hypotheses and facts]. AB - The notion that the development of certain gastrointestinal disorders and diseases can, at least in part, be ascribed to specific psychological characteristics of the patient, to an antecedent psychologically important event or to an unconscious conflict, is very popular both in the public and the medical profession. One of its earliest formulations was the conversion theory forwarded by Sigmund Freud, who assumed that the accumulation of a traumatic and unabreacted quota of affect induced defense or repression and caused a somatic conversion of emotion, i.e., a transformation into bodily symptoms. Subsequently, disorders such as globus sensation, diffuse oesophageal spasms and achalasia, the latter misconceived as "cardiospasm", were viewed as conversion symptoms. However, it has become clear that these disorders are the consequence of organic lesions and not of conversion. Similarly, concepts of an aetiological role of a specific psychological factor, a specific conflict, of certain affective states or live events and of "inappropriate perpetuations of organ reactions adaptive to, or protective against, some stress in human life" could not be verified. Although psychological characteristics and states have been shown to affect normal gastrointestinal function, there is no evidence to suggest that such influences can lead to gastrointestinal disorders or diseases. The fact that the validity of the concepts claiming such aetiological relationships remained to be tested has been repressed to such an extent in some quarters that these concepts still are advocated so as if they had been proven since long. PMID- 1926952 TI - [Diagnosis of biliary dyskinesia after cholecystectomy]. AB - In patients with upper abdominal complaints after cholecystectomy the normal and disordered bile flow was evaluated using quantitative scintigraphy after initially excluding organic etiology. A continuous intravenous infusion of cholecystokinin and secretin for one hour resulted in an accelerated bile flow in the majority of these patients, which is the normal reaction of the biliary system under stimulation. On the contrary, a bolus injection of these hormones led to marked delay of flow in a group of the study population, a condition taken as a paradoxical reaction to cholecystokinin. Although all of the patients with this paradoxical reaction did complain of typical biliary pain, a causal association is, however, yet to be proved. Nitrates can be helpful in the differential diagnosis of impeded bile flow, a lack of response being a possible sign of organic hindrance at the papilla of Vater. PMID- 1926953 TI - [Esophageal function in chronic alcohol abuse]. AB - 1. In our patients the chronic overindulgence in alcohol led to an increased appearance of a pathological gastrooesophageal reflux. Thereby the group with normal liver findings or steatosis showed a slightly pathological, the group with alcoholic liver cirrhosis a severe pathological reflux behaviour. 2. The manometric findings in form of a decreased resting pressure in the inferior oesophageal sphincter, a slightly increased duration as well as of a decreased speed of the contraction wave were certainly insignificant in functional respect. They could not explain the pathological reflux behaviour. 3. The chronic abuse of alcohol did not lead to erosive changes of the mucous membrane in the distal oesophagus. PMID- 1926955 TI - [Gastrointestinal motility disorders in diabetes mellitus]. AB - Diabetic patients are prone for the development of autonomic neuropathy with inclusion of the gastro intestinal system. The patients are mainly bothered by disturbances of motility. Depending on the localisation they manifest themselves as constipation or diarrhea. The knowledge of these complications is important, since therapeutic decisions may be influenced. PMID- 1926954 TI - [Disorders of anorectal function]. AB - Since sophisticated function tests of the anorectal continence organ become more and more available, dysfunction of the anorectum is increasingly diagnosed and differentiated. The examination includes measurements of the pressure in the rectum and anal canal (anorectal manometry), rectal distension by an inflatable balloon to test the sensibility, electromyography and radiological defecography. By these methods the etiology and pathogenesis of the most important anorectal disorders, such as anal incontinence, different forms of constipation and rectal prolapse, may be differentiated. Nowadays, many of these disorders are successfully treated by a specific management which includes a special diet, drugs, surgery and biofeedback training programs. PMID- 1926956 TI - [Prevention of HIV infection (AIDS)]. AB - Principal elements of the HIV- and AIDS-prevention in the social field and health care are discussed. The infection with HIV as a sexually transmitted disease can only be prevented by personal caution in the sexual behavior. Counselling should in particular be addressed to risk groups such as homosexuals and drug abusers early enough and contribute to practising safer sex. General rules of behavior and of the hygienics in hospitals are described. The risk of infection by blood transfusion is relatively low, namely 1:300,000 to 1:3 Mio. The modalities of optional anonymous epidemiologic system of registration (report, testing, counselling, care) are discussed. Finally problems of the development of a HIV vaccine are described, and the necessity to avoid discriminations of HIV infected or endangered persons is underlined. PMID- 1926957 TI - [Professional confidentiality of the physician]. AB - Summarizing it is to be mentioned that, concerning the professional secrecy, the principle is held that the physician is allowed to speak as much as it is necessary and he must be silent as far as it is possible. The physician is entitled to reveal but not obliged to do so as far as he has been exonerated from the professional secrecy or as far as the revelation is necessary for the protection of a higher legal proceeding. This is taken into consideration also for evidence in judicial proceedings. Apart from legal informational obligations at first, however, not the physician but the patient defines the breadth of allowable infringements. Only when the professional secrecy collides with the legal matters of third persons the physician himself gets into compulsions of decision. Taking into consideration the criminal law the maintenance as well as the infringement of the professional secrecy remain without consequences for the physician, if the translegal critical state is present. In such cases, however, he should endeavour to keep the dangers which brings his silence for others as insignificant as possible. PMID- 1926958 TI - [A modified monopolar electrocoagulation probe for endoscopic treatment of gastrointestinal hemorrhage]. AB - A modified monopolar electrocoagulation probe for endoscopic treatment of gastrointestinal bleedings in special situations is described. The tip of the active electrode may be moved foreward or drawn back into a teflon catheter. Thereby, blood clots are removed from the tip of the probe. The device is easy to use, reliable in emergency endoscopies and can be employed with conventional high frequency diathermy instruments. The probe is inexpensive. 49 patients with active gastrointestinal bleedings according to Forrest Ib were treated. In 40/49 patients permanent hemostasis could be achieved. In 4/49 patients recurrent bleedings were controlled after repeated electro-coagulation. 4/49 patients needed elective operation, one patient emergency operation. Complications by application of the described monopolar electrocoagulation probe did not occur. The area of necrosis according to electrocoagulation was small. PMID- 1926959 TI - [Various genetic models in Crohn disease]. AB - Crohn's disease has a genetic predisposition. In the light of epidemiological data, especially the type of familial clustering, simple modes of inheritance can be excluded. At the first glance, our results implied a polygenic multifactorial basis. Further processing of our data by the "mixed model" of Morton revealed a higher probability for a recessive gene with low penetrance. However, the differences in fit between the various models are relatively slight. Also considering ascertainment problems, a definite decision concerning an appropriate model must be deferred until sure genetic markers have been identified. Nevertheless, only a certain number of manifestations may be ascribed to a genetic predisposition, others have to be catagorized as phenocopies. PMID- 1926960 TI - Enhanced proliferative response to beta-endorphin of phytohemagglutinin-activated lymphocytes from patients with ulcerative colitis. AB - We investigated the effect of a known T cell mitogen, phytohemagglutinin (PHA) and the neuropeptide beta-endorphin on the in vitro lymphocyte proliferative response in patients with ulcerative colitis and in health persons. We found that patients with ulcerative colitis show enhanced reactivity to PHA, when incubated in the presence of beta-endorphin. The activity of the disease during the period of the investigation seemed to play no role, since lymphocytes from both patients in exacerbation or remission reacted in a similar manner. PMID- 1926961 TI - The effect of propranolol on thyroid function in patients with liver cirrhosis. AB - The effect of propranolol on thyroid hormones of 7 healthy subjects and 10 patients with histologically proven alcoholic liver cirrhosis was investigated. The fractions of plasma T3 and free T4 were determined by specific radioimmunoassay before and after two weeks of propranolol administration. Under basal conditions, both T3 and FT4 levels were found significantly lower in patients with cirrhosis than in healthy subjects (1.86 +/- 0.10 vs. 1.18 +/- 0.41 nmol/l, p less than 0.001; 9.31 +/- 0.41 vs. 8.17 +/- 0.91 pg/ml, p less than 0.05, respectively). In healthy subjects propranolol administration led to a significant reduction of T3 serum levels (from 1.88 +/- 0.10 to 1.51 +/- 0.12 nmol/L, p less than 0.001), while in patients with liver cirrhosis no significant changes in T3 and FT4 were found. In patients with liver cirrhosis propranolol administration did not affect thyroid hormone levels. PMID- 1926963 TI - [Celiac disease in the adult--a case report]. AB - The diagnosis of celiac disease is often missed particularly in cases of adult onset. We report the case of a man in his seventh decade who had been treated for many years for endocrine symptoms and signs of malabsorption. The first biopsy diagnosis of celiac disease was ignored. After a second jejunal biopsy, adequate treatment with a gluten-free diet was initiated. This resulted in recovery. The fact that celiac disease may often present for the first time in adults and that symptoms are not always clear are stressed as well as screening for the disease with the aid of endoscopic techniques. PMID- 1926962 TI - [Gastroenterologic findings in graft versus host disease after allogenic bone marrow transplantation]. AB - We are reporting on a 25 years old patient with acute myelogenous leukemia, who developed an acute graft-versus-host disease (GVHD) 43 days after allogeneic bone marrow transplantation (BMT). The clinical symptoms included exanthema, diarrhea and abdominal cramps. The patient was treated with cyclosporine A and prednisone and the clinical symptoms disappeared subsequently. At day 225 post BMT the patient became icteric as the clinical manifestation of chronic GVHD. We describe in this case report endoscopical and histological findings during the episodes of acute and chronic graft-versus-host disease. The results obtained by sigmoidoscopy and liver biopsy confirmed the clinical diagnosis. The clinical work up of patients with acute or/and chronic GVHD should also include sigmoidoscopy in order to verify this transplantation related complication. PMID- 1926964 TI - [Free transverse colon perforation in a hemophilic HIV-infected patient with diarrhea and fever]. AB - We describe a case of free perforation of the transverse colon in a patient with HIV-infection. No underlying infectious agent could be identified. Differential diagnosis is discussed. This case demonstrates the need for increased attention for unexpected complications of acquired immunodeficiency syndrome ever after a ten year experience. PMID- 1926965 TI - [Prevention of recurrence after successful gallstone dissolution]. AB - Gallstone recurrence is a major problem in the medical treatment of gallstones (treatment with UDCA/CDCA, ESWL, local MTBE lysis). The probability of gallstone recurrence is higher in subjects with multiple stones before dissolution treatment and in older subjects (greater than 50 years). The present knowledge on factors predictive of gallstone recurrence and the results of clinical trials for preventing recurrence are given. The different effects of diet and drugs on cholesterol saturation of bile, on nucleation of bile, on mucus production of gallbladder and on gallbladder contractility are discussed and recommendations for a rational approach for prevention of gallstone recurrence are given. Preventable risk factors for gallstone disease have to be eliminated. In general, continuous post-dissolution treatment seems not justified. Regular follow-up ultrasound examinations should be started to detect renewed of gallstones at an early stage. PMID- 1926966 TI - [Percutaneous liver biopsy in ambulatory patients]. AB - Percutaneous liver biopsy is a relatively safe procedure. Performance in an outpatient facility is acceptable for many patients. Complications are rare and usually will be recognized within a few hours after biopsy. In most cases, therefore, an observation of six hours is sufficient. Since complications occasionally occur delayed, there must be the possibility to return for hospitalization. PMID- 1926967 TI - [Ursodeoxycholic acid plus lovastatin for litholysis?]. PMID- 1926968 TI - [Reproducibility of continuous wave Doppler studies in pregnancy]. AB - The inter- and intraobserver variability of Doppler flow velocimetries of uterine, arcuate and umbilical arteries was studied using a 4 MHz continuous wave system in the second and third trimester of pregnancy. There was no significant variation in indices used to characterize the maximum frequency outline of waveforms of uteroplacental and umbilical arteries neither when two observers examined the same patient nor the examination was performed several times on the same day or over a 24 hour period by the same observer. In uteroplacental and umbilical arteries continuous wave measurements are highly accurate and are not inferior to the more expensive pulsed Duplex systems. PMID- 1926969 TI - [Ultrasound Doppler sonography in obstetrics. A comparison between simple Doppler methods (continuous or pulsed Doppler) and the duplex system (combination of B image and pulse Doppler)]. AB - 120 pregnant women between the 26th and 42nd week of gestation have been examined using simple Doppler-units with pulsed- or continuous-wave technique and duplex Doppler-units (combined B-mode and pulsed-wave Doppler). The umbilical and uterine arteries were measured with both units in a semi-recumbent position at the same time by the same examiner. Only ideal flow profiles were taken to calculate the S/D-ratio. Our results were correlated to the fetal outcome, to all cases of pre-eclampsia and to all cases of intra-uterine growth retardation. Except in one of these cases we got the majority of pathological results using simple Doppler-units. Only in pre-eclampsia the duplex Doppler-units had the majority of pathological results. Even in normal fetal outcome the majority of simple Doppler-unit results are pathological. This finding is due to the impossibility to localize the vessel exactly using simple Doppler-units. Sensitivity is higher in simple Doppler-techniques (74.3% to 52.9%), specificity is higher in duplex Doppler-technique (77.9% to 52.6%). PMID- 1926970 TI - [Vaginal sonography in the 1st trimester. I. Qualitative parameters]. AB - To establish exact data about the ultrasound image of early pregnancy and the detection rate of relevant structures, the vaginosonographic examinations of 259 normal intrauterine singleton pregnancies with reliable dates between 4 and 13 complete weeks menstrual age were analysed. The chorionic cavity as the first specific structure of pregnancy, was imaged in all cases. The chorion frondosum could be differentiated from the chorion laeve at 6/7 weeks. The yolk sac was reliably seen at 5 weeks. The embryo and its heart activity proving viability of pregnancy, were regularly found at 6 weeks. At 7 weeks the amnion was seen separately from the embryo. At 7/8 weeks its cranial pole and the umbilical cord were reliably identified. At 8/9 weeks the extremities as well as body movements were visible. Vaginal sonography is a valuable tool to examine early pregnancy and to prove its normal development. Visualization of the sequentially appearing structures may be also helpful to estimate gestational age. PMID- 1926971 TI - [Sonographic biometry of fetal organs]. AB - Over a period of 18 months measurements of fetal Organs (cornu anterius of the lateral ventricle, medium diameter of the four-chamber-view of the heart, transverse diameter of lungs, stomach, gall bladder, colon and urinary bladder) were carried out in a population of 223 normal pregnancies. The measurements were correlated to the age of pregnancy and sonographic growth parameters (biparietal diameter--BPD, mean cephalic diameter--MCD, mean abdominal diameter--MAD). The results show different growth velocities of the particular organs, obviously depending on physiological function. The variability is increasing with fetal growth. We found no fundamental difference as far as correlation of organ measurements to age of pregnancy, to BPD, MCD or MAD. In summary the imaging and biometries of the fetal organs appear to be possible in relatively little time and such is a valuable method for the detection of fetal anomalies. PMID- 1926972 TI - [Causes of and change in bacterial infections in newborn infants]. AB - Despite all the progress made in modern neonatology the morbidity rate caused by bacterial infections has rather gone up than down. The reasons why premature and newborn infants have a greater disposition to bacterial infections have been largely explored; at the same time one must accept these infants to be increasingly vulnerable to infections, the vulnerability being the larger the greater the degree of immaturity is. Every 5th to 10th death of newborn infants is caused by infection. One will have to be constantly on the watch and acquire profound knowledge of channels of infection and the bacterial spectrum to be expected. Since the early beginnings of neonatology, some 60 years ago, a continuous change in bacterial spectra has been going on showing incredible regularity in crossing even borders and continents. With gram-positive cocci (A streptococci) prevailing at the beginning, there was a considerable increase in gram-negative enterobacteriaceae in the 60ies and 70ies, when neonatal intensive medicine was started. There were mainly nosocomial infections resulting from too generously administered antibiotics. Today, plasmacoagulase-negative staphylococci, for a long period thought not to be pathogenous, are the essential bacteria in nosocomial infections. On the whole, one usually has to do with infections vertically transmitted by the mother, especially to preterm infants. The greatest threat still comes from B streptococci since they will lead to pulmonary changes such as pneumonia and RDS. The development reported on is based on data from the literature and my own experience as well as on comprehensive results of the Neonatalerhebung of Lower Saxony and Bavaria. PMID- 1926973 TI - [Anxious hostile behavior as a precursor of pregnancy-induced hypertension]. AB - In 127 healthy pregnant women of the 27th and 28th gestational week, the influence of somatic and affective disorders was investigated with regard to pregnancy-induced hypertension (PIH) after the 30th gestational week prospectively. The women answered a five step self-rating scale including 28 somatic and affective symptoms. The incidence of PIH achieved 12.7%. The PIH group rated disorders significantly higher than the group without PIH (p less than 0.001). The self rated anxious hostile behaviour disorders were significantly stronger in the PIH-group than in the controls. So, in our sample anxious hostile behaviour appeared to be precursor of PIH. Somatic and affective symptoms of anxiety and hostility are provocated by adrenaline and noradrenaline typically. Catecholamines stimulate synthesis of prostaglandins, favouring PGF and TX. The resulting imbalance of prostaglandins appears to cause PIH pathognomonically. There is discussed that persisting anxious hostile behaviour is able to induce PIH by catecholamine-prostaglandin-mechanism. PMID- 1926975 TI - [Prenatal rubella diagnosis]. AB - Primary rubella infections during the first trimester of pregnancy are an indication for the termination, although not all of fetuses will be infected. Concerning this situation a prenatal rubella diagnostic in 55 pregnant women was carried out to demonstrate a fetal infection. Simultaneously or separately, as methods the determination of rubella IgM antibodies in fetal blood, the demonstration of viral RNA by DNA-RNA-hybridization and the cultivation of rubella virus from amniotic fluid samples were used. In 7 of 40 women the investigation of amniotic fluids showed a positive reaction of the hybridization, in 2 cases a rubella virus could be isolated. IgM rubella antibodies were found in 5 fetuses. Because of its insufficient effectivity at present the prenatal rubella diagnostic should be applied only in special situations, e.g. in cases of a wanted child. PMID- 1926974 TI - [Patau syndrome without trisomy karyotype? Danger of restricted thinking in syndrome diagnosis]. AB - By means of a case-report the problems of an uncritical usage of the terminus "syndrom" are pointed out. The report concerns with a newborn child clinically showing nearly all morphological characteristics of the "Patau-Syndrom" without having a chromosomal aberration. PMID- 1926976 TI - [Anxiety disorders and anxiety attacks: diagnosis and treatment from the viewpoint of behavior therapy]. AB - Fear disorders and anxiety attacks are central disorders in clinical psychology and psychotherapy. In the study at hand, theoretical possibilities of explanation are treated according to the assumption of the Kanfer's theory of human behavior (classic and operant conditioning, model learning, cognitive theory) and specific therapeutic interventions (systematic desensitization, model learning, confrontational therapy, cognitive behavioral therapy). These are described via case histories of a simple and a complex phobia. Following this, controlled evaluation studies pertaining to specific anxiety therapy are described. PMID- 1926977 TI - [Is the concept of the anti-type dispensable? Answer of the mixed distribution approach to an IPC anti-type]. AB - The hypothesis based on the MDS-structure of related personality profiles was that the anti-type-configurations of a three-variate 2x2x2-data-vector as well as the statistically neutral configurations are merely consequences of the combined distributions of the responses resulting from two latent classes related to the types found in the data-vector by configural frequency analysis. This hypothesis was confirmed with a data set originating from dichotomized distributions of a three-variate measure of generalized locus of control. The conceptualized configural error model (CEM) is proposed as a general supplement to configural frequency analysis (CFA). PMID- 1926978 TI - [Development of a procedure for community psychological field research: the Contact Analysis Questionnaire]. AB - Numerous community psychology oriented research designs do not sufficiently take into consideration real processes of exchange between person and environment. With the target to enrich community psychology empirically we developed a structured interview scheme for the description of interpersonal transactions. Random samples of self-registered social interactions can be analysed ex posteriori context- and contentwise by the "Kontaktanalysebogen". Following explications and instructions for each paragraph first results concerning objectivity and acceptance in field research are reported. Target groups in particular are individuals threatened by social isolation, e.g. former mental patients. Some empirical results of our own study are given. PMID- 1926979 TI - [Prognostic factors for long-term survival in anorexia nervosa]. AB - This work describes the results of a long-term follow-up (mean duration = 13.5 years) of 105 female anorexia nervosa patients, for 93.3% of whom (n = 98) we were able to obtain information. Our objective was to identify factors affecting the long-term prognosis in these cases. Weight gain and a stable partnership after treatment as well as high body weight on termination of treatment were shown to be especially important for long-term recovery. This suggests the following for treatment of anorexia nervosa: besides restoration of normal body functions, the patient should attempt to leave her parents' home and enter a partner relationship. Further weight gain should not be neglected during this process. PMID- 1926980 TI - [Self concept of children and adolescents: development and use of the Self Concept Assessment List]. PMID- 1926981 TI - [Myocardial contrast echocardiography with sonicated iopromide (Ultravist 370) before and after coronary angioplasty]. AB - Thirty-one patients (3 female, 28 male, mean age 56 years) were investigated with myocardial contrast echocardiography before and after successful PTCA (= less than 30% residual stenosis) of one major coronary artery. 2 ml of sonicated lopromid (Ultravist 370, microbubble-size 6 +/- 4 microns) were injected into the coronary vessel. Before, during and after injection a short-axis view or an apical four chamber view was obtained and recorded on videotape. Computer assisted videodensitometry was performed in a region of interest placed between endo- and epicardium of the myocardial area supplied by the dilated vessel to analyze contrast decay half-time (t/2), time from onset of opacification to t/2 (T-t/2) and maximal videointensity (Imax). 27 patients (87%) had adequate echorecordings before and after PTCA, no side-effects occurred. Contrast decay half-time and T-t/2 showed a decrease in 21/27 (78%) patients (8.7 +/- 6.1 vs 5.8 +/- 3.7s, p less than 0.001) and in 19/27 (70%) patients (12.0 +/- 8.4 vs 8.7 +/- 5.0 s, p less than 0.002) respectively. Imax was not significantly altered by the intervention. Most of the patients without decrease of t/2 and T-t/2 either had moderate coronary stenosis or a preexisting myocardial infarction in the region supplied by the dilated vessel. Thus contrast echocardiography seems to be suitable to assess alterations in myocardial blood flow during PTCA by determination of contrast decay half-time and T-t/2. PMID- 1926982 TI - [Intraoperative contrast echocardiography using sonicated iopromide (Ultravist 370) for imaging the post-bypass myocardial region]. AB - In order to minimize the rate of inadequate myocardial revascularizations, an intraoperative evaluation of regional myocardial perfusion could have practical impact. Current bypass flow measurements have inherent limitations and can determine only epicardial blood flow. To analyze regional graft-dependent myocardial blood flow an echocardiographic short-axis view of the left ventricle was performed intraoperatively in 11 patients undergoing elective coronary artery bypass surgery. After injection of 2 ml of sonicated lopromid (Ultravist 370) into 14 vein grafts, contrast enhancement in the corresponding myocardial regions was clearly visible, no side-effects occurred. Contrast decay halftimes (T/2) were determined by computer-assisted videodensitometry and compared to electromagnetic flow (EMF) rates, which were measured immediately before. T/2 ranged from 2.1 to 6.9 (mean 4.1 +/- 1.5) s and did not correlate to the EMF rates of 55 to 100 (mean 80 +/- 16) ml/min. Thus intraoperative myocardial echocardiography is a safe and feasible method which allows on-line visualization and off-line quantitation of regional myocardial perfusion intraoperatively. PMID- 1926983 TI - [Therapeutic value of trans-esophageal electrostimulation in tachycardic arrhythmias]. AB - We were able to terminate atrial flutter in 136 of 162 patients by transesophageal rapid atrial stimulation (conversion to sinus rhythm in 75 cases, induction of atrial fibrillation in 61 cases). Atrial tachycardias were interrupted in 17 of 23 patients (sinus rhythm in 11, atrial fibrillation in 6 cases), AV reciprocating resp. AV nodal supraventricular tachycardias were terminated in 32 of 33 patients (sinus rhythm in 28 cases, atrial fibrillation in 4 cases). By transesophageal rapid ventricular and/or atrial pacing, ventricular tachycardias could be terminated in 10 of 15 patients. The success rate of transesophageal pacing is influenced by the type of tachyarrhythmia, by the type of atrial flutter and by the stimulation rate. It is not influenced by the tachycardia's cycle length. Because the success rates are comparable with invasive technique and the procedure is simpler, the non-invasive transesophageal antitachycardia pacing represents a useful method for termination of tachycardic arrhythmias. PMID- 1926984 TI - [Induction of arrhythmia by licorice abuse]. AB - We report two cases of licorice-induced arrhythmias. In both cases the ingestion of large amounts of licorice caused a marked hypokalemia. The importance of licorice-induced hypokalemia for the development of arrhythmias is underestimated from the small number of published cases. We conclude that patients with a predisposition for arrhythmias should avoid licorice candies. PMID- 1926985 TI - [Treatment of chronic stable angina pectoris with angiotensin converting enzyme inhibition--a randomized, placebo-controlled, double-blind cross-over study]. AB - To investigate the potential anti-ischaemic effects of benazepril (10 mg bid) in comparison to placebo, this new ACE-inhibitor was given to 11 patients with chronic stable angina, reproducible exercise-induced ST-segment depression and angiographically verified coronary artery disease. Blood pressure at rest, plasma renin activity, and plasma concentration of atrial natriuretic peptide were measured after treatment periods of two weeks. Bicycle exercise tests at the same time should evaluate ST-segment depression at comparable maximal workload, work capacity, blood pressure, and heart rate at exercise. In comparison to placebo, benazepril reduced arterial blood pressure significantly from 140 +/- 14/90 +/- 11 mm Hg to 125 +/- 16/84 +/- 10 mm Hg (p less than 0.05) and increased plasma renin activity from 2.19 +/- 3.76 ng/ml/h to 9.62 +/- 8.49 ng/ml/h (p less than 0.005). In contrast, ST-segment depression decreased only slightly and not significantly from 2.09 +/- 1.22 mm to 1.91 +/- 1.00 mm. Benazepril had neither an effect on the frequency of episodes of angina pectoris nor did it reduce the amount of GTN-consumption. Also, work capacity and plasma concentration of atrial natriuretic peptide were not changed in comparison to placebo. Although the significant reduction of blood pressure and the highly significant increase of plasma renin activity demonstrate the specific action of benazepril, a significant anti-ischaemic effect could not be established. PMID- 1926986 TI - [Transluminal excimer laser angioplasty of experimentally-induced atheromatous plaque: morphologic changes and importance of proliferation of smooth muscle cells]. AB - To determine the time-course of morphological changes after excimer laser treatment of atherosclerotic carotid arteries, laser angioplasty was performed in 34 rabbits after production of an intimal plaque (13 +/- 6 cell layers, 30 +/- 9% stenosis) using electrical stimulations. The animals were sacrificed 3, 7, 14, 21, 28, and 42 days after laser treatment. A total or subtotal thrombotic occlusion was found in four cases. No perforation was observed, but in 10 animals histological examination evidenced a partial ablation of the medial layer with signs of local thrombus formation and local reduction of SMC in the media. In five animals a stenosis of more than 50% of luminal reduction was due to intimal proliferation of smooth muscle cells (SMC), as determined by a monoclonal antibody against alpha-actin. After the initial ablation, a continuous increase of intimal cell layers was found, from 7 +/- 6 cell layers (19 +/- 9% stenosis) at 7 days, to 28 +/- 5 cell layers (45 +/- 18% stenosis) at 28 days following excimer laser angioplasty (p less than 0.01). After 42 days no additional increase of intimal thickening occurred. Our data suggest that incidence and morphology is comparable to the proliferative response of SMC following conventional balloon angioplasty. PMID- 1926987 TI - [Percutaneous transluminal coronary angioplasty (PTCA) in unstable angina pectoris: results and complications with reference to a new classification]. AB - Percutaneous transluminal coronary angioplasty (PTCA) of patients with unstable angina pectoris is an established therapy, although the rate of major complications (death, myocardial infarction, emergency coronary artery bypass operation) is higher than in patients with stable angina. This study analyzes the results of PTCA in 168 patients (136 men, 32 women, mean age 60.6 +/- 9.6 years) treated between January 1989 and June 1990 for unstable angina pectoris. Unstable angina was classified according to the criteria proposed by Braunwald in 1989. PTCA was successful in 141 patients (83.9%) and failed in 27 patients (16.1%). No patient died. One patient (0.6%) suffered an acute myocardial infarction related to PTCA. After failed PTCA 16 patients (9.5%) underwent emergency coronary artery bypass grafting (CABG), 10 patients had no complication. In patients of unstable angina class III (angina at rest within the last 48 h before PTCA) emergency CABG was needed in 20.3% compared to 3.6% (p less than 0.01) in patients with unstable angina class II (last attack of angina at rest more than 48 h before PTCA). Also 30% of patients with unstable angina within 2 weeks after myocardial infarction (clinical subgroup C) needed emergency CABG after failed PTCA as compared to only 6.9% (p less than 0.01) of patients with primary unstable angina pectoris without previous infarction (clinical subgroup B). The highest frequency (66.6%/6 of 9 patients) of emergency CABG was observed in patients with class III and subgroup C. We conclude that the classification of unstable angina pectoris proposed by Braunwald might be helpful to identify patients with risk in PTCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1926988 TI - [Main branch stenosis following aortic valve replacement]. AB - Three patients developed left main stem stenosis within some months after aortic valve replacement. In all of them diagnosis was confirmed by angiography and bypass surgery was performed successfully. Left main stem stenosis is a rare complication of aortic valve replacement and is due to cannulation and perfusion of the coronary arteries. The mechanism is probably injury of the vessel wall due to the perfusion-catheter, followed by intimal hyperplasia. A similar mechanism is assumed for restenosis after transluminal coronary angioplasty. PMID- 1926989 TI - [Doppler echocardiographic determination of the effective orifice area of mechanical heart valve prostheses in a flow model]. AB - In a flow model the effective orifice areas (Ae) of 17 mechanical heart valve prostheses were determined. We measured the Ae-values of several sizes of three types of mechanical prostheses (Medtronic-Hall, St. Jude Medical, and Omnicarbon) under quasi-steady flow conditions using the continuity equation: Ae = flow/maximal transprosthetic velocity. The flow through the model could be determined exactly by directly measuring the decreasing fluid level within the feed tank, while the maximal velocities were calculated from CW-Doppler echocardiographic spectra. It was found that 1) over a range of 200-800 cm3/s Ae was constant for all prostheses and 2) in small aortic prostheses the Ae could be determined with only little scattering of the obtained values, while in large mitral prostheses there was a considerable variation within the results of repeated investigations. For example, in the 21- and 31-Omnicarbon-valves mean values of Ae were calculated as 1.41 and 4.03 cm2, respectively, with standard deviations of 0.05 and 0.49 cm2 as a result of about 70 single calculations in each valve. 3) The absolute values of Ae were smaller than those of comparable in vitro studies based on the Gorlin formula. We conclude that the effective orifice areas of prosthetic heart valves can be easily determined in a flow model by the combination of flow and Doppler echocardiographic measurements. As determinations are based on the same principle, the obtained values should clinically be referred to patients where the corresponding continuity equation for pulsatile flow is used as Ae = stroke volume/time integral of the maximal transvalvular velocity. PMID- 1926990 TI - [Magnetic resonance rheography in comparison to Doppler ultrasonography in the assessment of mitral valve stenosis]. AB - Ultrasound-Doppler-technique and heart catheterization today are used routinely for the evaluation and graduation of mitral valve stenosis. A new magnetic resonance-technique of intracardial blood-flow registration now allows the grading of mitral valve stenosis. Good reliability and practicability of the demonstrated method in comparison with the ultrasound-Doppler-technique is shown. Future development of an alternative, completing magnetic-resonance method for the evaluation of valvular heart disease and shunt diagnosis is expected. PMID- 1926991 TI - [Experiences with the application of monoclonal Indium-111 antimyosin scintigraphy in the diagnosis of rejection episodes following orthotopic heart transplantation]. AB - Indium-111-labeled Fab fragment imaging using a murine antimyosin monoclonal antibody (Myoscint, Centocor, Leiden) was evaluated for efficacy in detecting cardiac allograft rejection. Diagnosis of rejection was made by endomyocardial biopsy with four to five samples taken for each procedure. Eighty-one studies were performed in 25 patients (21 men, four women, mean age 50 +/- 9 years) from 2 weeks to 45 months after cardiac transplantation. 0.5 mg of the monoclonal antibody labeled with 60 MBq Indium-111 (Antimyosin-Fab-DTPA) was administered i.v. Planar scintigraphic images were obtained in LAO 45 and anterior projections as well as "half-body-scintigrams" 48 h after injection. Using the regions-of interest-(ROI)technique the relative uptake over the lung and the heart was determined and an index of In-111 uptake was calculated. A heart-to-lung ratio of 1.5 or higher was considered indicative for moderate to severe rejection. Specificity was 86% (nine false-positive In-111 studies in 68 negative biopsy studies), sensitivity was 85% (two false-negative In-111 studies in 13 pathological biopsy studies). It is concluded that the In-111 method has a high sensitivity and specificity in detecting heart transplant rejection and may be useful in the monitoring of patients in the chronic phase after heart transplantation. The 48-h delay in establishing the diagnosis limits the applicability in acute severe rejection. PMID- 1926992 TI - [Heart-minute volume during persistent ventricular tachycardia: anti-arrhythmia intervention using ajmaline]. AB - The hemodynamic effect of the intravenous application of ajmaline (50 mg) was studied during persistent ventricular tachycardia. With the onset of ventricular tachycardia an increase of heart rate up to 177 +/- 40 bpm and a simultaneous decrease of cardiac output from 7.1 +/- 2.7 l/min to 3.4 +/- 1.1 l/min (p less than 0.001) could be demonstrated. Ajmaline prolonged the QRS interval and slowed the ventricular tachycardia rate to 133 +/- 28 bpm. Simultaneously, an increase of cardiac output to 5.9 +/- 2.3 l/min (p less than 0.001) could be documented. A significant correlation between the increase of cardiac output and the change of ventricular tachycardia rate was found. A drug-induced termination of ventricular tachycardia by ajmaline was possible in 60% of patients. Intravenous application of ajmaline during persistent ventricular tachycardia leads to a hemodynamic improvement caused by the reduction of the tachycardia rate. This temporary stabilization of the hemodynamic status is important for emergency treatment of ventricular tachycardia. PMID- 1926993 TI - [The effect of step rate and muscle force on the rate response of activity modulated cardiac pacemaker]. AB - Programming of activity-modulated pacemakers allows an individual adaptation of rate response. In 26 pacemaker patients (Activitrax n = 16; Synergyst n = 10; Medtronic) it was tested whether rate-response parameters can already be programmed under consideration of patient's characteristics. At a fixed rate response setting (VVIR/VOOR mode, pacing rate range: 60-130 ppm, MEDIUM/7) four treadmill exercise tests were performed: three step-rate controlled tests with 40, 80, and 120 steps/min and a symptom-limited exercise test with 1 km/h initial speed and 1 km/h speed increments every second minute. Maximal pacing rates at 80 steps/min (72 +/- 14 ppm) and 120 steps/min (90 +/- 6 ppm) were higher than at 40 steps/min (63 +/- 6 ppm). Forced steps with a step rate of 40/min resulted in a higher pacing rate compared to normal steps. At symptom-limited exercise, maximum pacing rates increased to 102 +/- 19 ppm with a range from 60 ppm to 124 ppm. Positive correlations were found between maximum step rate and maximum pacing rate (r = 0.55), between exercise duration and maximum pacing rate (r = 0.70), and between exercise duration and maximum step rate (r = 0.78). Patients with an exercise tolerance up to 5 km/h achieved pacing rates from 91 and 124 ppm, but patients with restricted exercise tolerance had lower maximum pacing rates due to their lower maximum step frequencies. Step rate and body force are important movements in the generation of body vibrations. PMID- 1926994 TI - [Right ventricular outflow obstruction due to accessory tricuspid valve tissue in corrected transposition of the great arteries with ventricular septal defect]. AB - A 27-year-old man known to have corrected transposition of the great arteries (CTGA) associated with a ventricular septal defect (VSD) was admitted to our hospital with a suspected increase of the shunt volume. The patient is a first class bodybuilder. Heart catheterization confirmed the diagnosis of a "right ventricular" mass obstructing the "right-ventricular" outflow tract, which had already been seen at echocardiography. The intraoperative finding showed the tumor to be accessory tissue of the anterior tricuspid leaflet prolapsing through the VSD into the subvalvular outflow tract of the right ventricle. The accessory tricuspid valve tissue was removed by transatrial access. The VSD was closed by a dacron patch using the same route. The postoperative course was uneventful. PMID- 1926995 TI - [Comment on the publication by J. Weirich and H. Antoni "Current aspects on the rate-dependent effect of Class-1 anti-arrhythmia agents. Critical analysis of the usual subclassification" in Z Kardiol 80:177-186 (1991)]. PMID- 1926996 TI - [Main branch dissection of the left coronary artery following excimer-laser angioplasty]. PMID- 1926997 TI - [Effects of the phosphodiesterase III inhibitor in ischemic heart disease]. AB - Positive inotropy requires a rise in myocardial oxygen consumption (MVO2); as far as PDE-III-inhibitors' beneficial hemodynamic effects, increases in contractility are controversial, in part probably because accurate proving is rather tedious. The clinician, however, requires a clear concept of whether or not enoximone (EN), for example, carries the risk of myocardial ischemia when used in patients with coronary artery disease. Using the analysis of pressure-volume relations, we recently established contractility-increasing as a partial effect of EN. There are indications suggesting that the inotropy-induced added increase in MVO2 of the PDE-III-inhibitor drugs could be compensated for by the simultaneous vasodilation and changes in compliance, so that as a net effect an unchanged MVO2 might result. Since, on the other hand, PDE-III-inhibitor drugs have been said to generate antiischemic properties, further clinical investigations with EN clearly seemed indicated and they are the subject of the present report: In five patient groups with stabile angina (AP) studied the following parameters and methods, respectively, were used for the evaluation of EN-induced changes of the anginal threshold: exercise, using pacing and ergometry; PA- and PC-pressure measurements; MVO2, indirectly assessed; hemodynamic profile and regional wall motion as assessed in the immediate post pacing phase; ST- T-segment evaluation; thalium-201 perfusion scintigraphy; myocardial perfusion, indirectly assessed. Lack of EN-induced AP (ischemia) and an increased AP threshold indicated that the drug can be used safety in patients with heart failure, including that due to coronary artery disease. PMID- 1926998 TI - [Privation as a measure of the irreversibility of biological aging]. AB - Privation (imperfection) means the error-containing part of the structural and functional organization of an organismic system. Privation is used to measure the irreversibility of aging processes. Knowing the age rate beta it is possible to estimate the privation. Using the hypothesis that the biodynamical efficiency may not be greater than the inverse age rate beta, a dimensionless number is constructed, which is given by the product of age rate beta and the theoretical lifespan T. PMID- 1926999 TI - [Lipogenic enzymes of the lung in relation to age]. AB - The activities of lipogenic enzymes of the lung of female rats of the Wistar strain were measured in the age groups 3, 18, 21, 25, and 30 months. The activities of malic enzyme (EC. 1.1.1.40) and citrate cleavage enzyme (EC. 4.1.3.8) decrease in dependence on aging. In contrast, the enzymes of pentose phosphate shuttle glucose-6-phosphate dehydrogenase (EC. 1.1.1.49) and 6 phosphogluconate dehydrogenase (EC. 1.1.1.44) do not show an age dependence. PMID- 1927000 TI - [Biomechanics and aging]. AB - Starting from the physical basics of the biomechanics of connective tissues, organ structures and the corresponding age-related changes of skin, tendons, ligaments, cartilage, bones, blood vessels, and lungs are described. Finally, exogenous factors such as nutrition, hormones, immobilization, activity and adaptive mechanisms and their influence on the biomechanical properties of connective tissue are represented. PMID- 1927002 TI - [Surgery in advanced age]. AB - Between 1982 and 1990 724 patients aged between 85 and 102 years were hospitalized (average age: 88.7 years). Operations were performed on 482 of them (66.6%). The surgical mortality amounted to 16.8%. The mortality in conjunction with emergency operation was as high as 28.2%, or as low as 11.4% in the context of elective operations. X-ray findings recorded from heart and lung, and ECG provided reliable criteria for assessment of the surgical risk. PMID- 1927001 TI - [Procedure for determining various kinds of airway obstruction--informative content and significance for geriatrics]. AB - For testing the airway obstruction the flow volume curve, the body plethysmogaphy, the oscillation technique, the peak flow measurement were used. The flow volume curve and peak flow test are the most important tests on elderly patients. The body plethysmography is the reference method. The oscillation method is helpful, but rarely necessary. PMID- 1927003 TI - [Changes in cardiopulmonary capacity after pacemaker implantation in the elderly]. AB - Elderly patients often suffer from several diseases. A combination of heart failure and low heart rate causes a decrease of cardiopulmonary capacity in the elderly. Analysis of gas exchange during exercise allows to determine cardiopulmonary capacity. Twenty-one patients older than 70 years were examined by spioergometry, before and 1 week after implantation of a pacemaker. Blood pressure, breath-frequency, oxygen-uptake, carbon dioxide emission, and respiratory quotient were measured. One week after implantation of a pacemaker system, there was an improvement of cardiopulmonary capacity and oxygen uptake at the moment of aerobic-anaerobic exchange. An additional positive effect was seen in elderly patients after implanting a system with rate-response stimulation (VVIR). Elderly patients with bradycardia profit from the implantation of a pacemaker system. Rate-response stimulation seems to be more effective in increasing cardiopulmonary capacity in the elderly. PMID- 1927004 TI - [Methods of research in subjective time experience]. AB - The main aim of the study is to give a review of methods to analyse subjective time experience, e.g. interview techniques, psychometric scales, and events tests. An elaborated methodological inventory is now available in this area of research. But on the other side, the procedures to investigate time perspective are still rather heterogenous, especially with regard to various projective and graphic techniques which could not be described in the present study. Briefly discussed are terminological aspects and a theoretical model of subjective time experience and time perspective. PMID- 1927005 TI - Times, places, and mechanisms of falls among the elderly. AB - Elderly persons among the population aged 65 years or over in the town of Pori, Finland, falls leading to medical treatment experiencing during one year, are described by age, sex, month, time of day, place, mechanism, estimated cause, previous falls, symptoms before falling, and activity when falling. Results indicate that the falls can be divided into two main categories: falls due to an extrinsic mechanism such as slipping or stumbling, and falls due to an intrinsic or unknown mechanism. Extrinsic mechanisms are more common in the younger age group (65-74 years), in whom falls are dependent on the time of day and amount of activity, and frequently happen outdoors while walking. Thus, slipping is a common extrinsic mechanism. Intrinsic or unknown mechanisms are more common in the older age group (75 years and above), in which estimated causes, such as orthostatic hypotension, fever, dementia, or joint disorders, can in many cases be detected. These cases are not dependent on time of day or month. Falls due to intrinsic or unknown mechanisms are related to rising from a lying or sitting position and lifting the head or turning the body before the fall. Before falling, some kinds of symptoms are more commonly experienced by persons falling due to an intrinsic or unknown mechanism than by those falling due to an extrinsic mechanism. PMID- 1927006 TI - [Risk of breast cancer and oral contraceptives]. AB - Oral contraceptive pills have been made available to women since the beginning of the 1960s. The pill (oral contraceptive pill, ovulation inhibitor) is the most sure of all contraceptive methods. With the beginning of applicating the pill, there had been fear of increasing breast cancer risk due to contained hormones. It is assumed that every third woman had ever taken oral contraceptive pills in her life. Yet, breast cancer incidence did not increase world-wide in an extent as would have been expected if the pill really were operating in a breast cancer promoting manner. PMID- 1927007 TI - [Direct lymphography with special reference to peripheral lymphedema. Historical retrospect--technique--indications--alternative procedures--image documentation]. AB - Indication for direct lymphography during the past forty years shows a downward tendency, mainly because of new alternative modern imaging methods. Nevertheless, in agreement with the actual literature it can be shown by own investigations with 8000 patients from 1964 to 1989 that one cannot give up lymphography totally. On principle lymphography is still carried out in case of testicular tumors, malignant lymphomas, unclear fever, lymphatic vessel injury and facultative in peripheric lymph edemas. PMID- 1927008 TI - [Ultrasound diagnosis (sonography). Historical development--physical principles- clinical use]. AB - Ultrasound generation is known now since about 150 years. Echo sounding has been used in first world war to fix the position of submarines, now we apply the echo sounding method in medical imaging to representate and to distinguish organs and tissue structures. This requires good knowledge about physical and technological properties in ultrasonics and about tissue interaction with ultrasound waves. PMID- 1927009 TI - [On the way to understanding the lymphatic system]. PMID- 1927010 TI - [Health care under new management. Newly designed models promote alternatives in health care]. PMID- 1927011 TI - [Health care under new management. We want to be loose from County Council hierarchy. Cooperative remains the means for independent work. Interview by Kaj Nyman]. PMID- 1927012 TI - [Health care under new management. Not a chance that County Council will choose cooperative. Interview by Jan Thomasson]. PMID- 1927013 TI - [Health care under new management. Bonus money separates enterprise from a customary base]. PMID- 1927014 TI - [Health care under new management. Anxiety and dispute about bonus money. Interview by Jan Thomasson]. PMID- 1927015 TI - [A time of flowers with dark undertones]. PMID- 1927016 TI - [Maria Wine 1912-]. PMID- 1927017 TI - [Affection and service, are they necessary in nursing?. Interview by Carcina Roxstrom]. PMID- 1927018 TI - [This way we stay both healthy and a better community. Interview by Jan Thomasson]. PMID- 1927019 TI - [Hungarian Nurses' Organization selects way--professional direction should give members better working conditions]. PMID- 1927020 TI - [Profile of Hilma Tragard]. PMID- 1927022 TI - [Better acute care through team work with relatives]. PMID- 1927023 TI - [Kerstin was forced from her job without really knowing why]. PMID- 1927024 TI - [Birgitta Birgersdotter 1303-1373]. PMID- 1927021 TI - [Miami, Florida--AIDS clinic is a popular working place. Interview by Mats Nilsson]. PMID- 1927025 TI - [Vagval in the balance. 3 models for future health care]. PMID- 1927026 TI - [Phagocyte function in uremic patients]. AB - Phagocytosis is the process where specific cells, phagocytes, ingest foreign material, include it in a cytoplasmatic vacuole, called phagosome, and destroy it. The function of phagocytosis in the immune response has been underevaluated for a very long time. Phagocytosis however, appears to be more and more important in our defense against infection and cancer. The uremic patient presents a well known and increased tendency for infectious disease as well as an increased incidence of cancer. Modern methodology for investigation of phagocytic function consists of: 1. measuring the respiratory burst during phagocytosis; by examining the radio-active CO2 production during the glucose metabolization of phagocytosis. 2. During the chemical reaction of the respiratory burst light is produced. This chemiluminescence can be measured in a Lumetron. In uremia the registration of that chemiluminescence can however be disturbed by the presence of uremic toxins, acting as scavengers of free radicals. 3. Measurement of interleukin-1, interleukin-6 or tumor necrosis factor production during phagocytosis. In the present study, we investigated glucose metabolization and radioactive CO2 production without stimulation and after a challenge with Latex, Zymosan or Staphylococcus Aureus. All tests have been performed on 50 microliter whole blood samples. The following uremic situations have been investigated: 1. Several degrees of increasing renal failure. 2. First weeks of hemodialysis maintenance treatment. 3. Hemodialysis session. 4. Course of hemodialysis maintenance treatment. 5. Continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. 6. Changes after chemical stimulation by a cephalosporin (cefodizime (R)). The Authors report their detailed results of these investigations and conclude as follows: --uremia is a prototype of acquired immune deficiency. --Contact with bio-incompatible membranes during hemodialysis is disastrous for phagocytosis. --Other toxins than the classical urea or creatinine are apparently responsible for the phagocytic disturbances. - Stimulations of phagocytosis with medication such as the cephalosporin, Cefodizime(R) (Hoechst) is possible. PMID- 1927027 TI - [Midwifery education in Ghent: a historical sketch]. AB - In spite of the tremendous importance of the services of the midwife in past centuries, formal regulation of their office was delayed until the establishment of the Collegium Medicum Gandavense (1663). Formal instruction of Ghent midwives was belated even longer, the first school for midwives being established only in 1772. Two years later, the Castellania Auderburgensis started her own school for midwives, the Ecole Royale et Superieure d'Accouchements. Thus, it was Ghent's unique privilege to possess two schools for midwives in the latter fourth of the 18th century, one supervised by the city's medical college, the other by the Castellania of the Oudburg. Due to the charisma of its teacher (the famous man midwife J.B. Jacobs) and thanks to the fact that the jurisdiction of the Castellania comprised the greater part of the present-day provinces of East- and West-Flanders, the Ecole Royale became a tremendous success. Unfortunately, this school was short-lived: together with the Castellania it was suppressed by the French in 1795. The City School fared better. Indeed, its teacher (med. lic. Damman), by joining the Comite de Sante of the Departement de l'Escaut could rescue the institution and bridge the gap between the suppression of the Collegium Medicum Gandavense (1795) and the foundation of the Ecole de Chirurgie by the French administration (1801). Both the Ecole de Chirurgie and the other French "medical" schools of Gent [Ecole de Medecine, de Chirurgie et de Pharmacie (1805-1806) and Ecole elementaire de Medecine (1806-1817)] took care of the theoretical instruction of departmental midwives. Regretfully, the authorities did fail to make use of the opportunities granted by the French law and establish a "home for poor women" in their city. Had such been realized, midwives would have had a chance to obtain clinical training as well. For the latter we will have to wait another decade. Indeed, it was only at the end of his reign that king William I succeeded to persuade the local and provincial authorities of the dire necessity of establishing a maternity clinic with annexed school for midwives. The first Provincial Maternity Clinic was installed in 1828 in a building erected for this purpose at the Hoveniersdreef. Two years later, the medical students of the Ghent State University (founded by William I in 1817) were admitted to the school for clinical teaching, be it in separate quarters. Because the main purpose of the Maternity Clinic was the instruction of midwives, the medical faculty will be treated as "parente pauvre" for decades to come.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1927028 TI - Role of prostaglandin-mediated mechanisms during experimentally induced endotoxin fever in the lactating goat. AB - The effects of endotoxin (LPS) on the cortisol, glucose, NEFA (non-esterified fatty acids), STH (somatotropin) and oxytocin levels in plasma of goats are described. The changes in plasma cortisol, STH and NEFA, as well as in RT (rectal temperature) were compared after i.v. and i.mam. administration of endotoxin. The other parameters, glucose and oxytocin, were followed only after i.v. endotoxin administration. The observed metabolic and hormonal alterations in plasma were also studied after pretreating the goats with the non-steroidal anti-inflammatory and antipyretic drug flurbiprofen in order to evaluate the possible involvement of prostaglandin in these phenomena. After i.v. administration of LPS a biphasic temperature curve for the highest dose of LPS with peak maxima at 1h and 4h after LPS challenge, was observed. Intramammary administration of endotoxin induces a monophasic fever response, with a latency time of approximately 3h, and peak values after 6h. The onset of the fever response in the i.v. experiments coincided with the oxytocin maximum and with early hyperglycemia. Intravenous endotoxin in goats also induces an increase in plasma NEFA, cortisol and STH. The early increase in NEFA, with a maximum after 2h and occurring before the fever peak, is followed by a significant rise in cortisol with peak effects after 3 h. The increase in plasma STH coincided with the decrease in plasma NEFA returning to control levels again. Peak concentrations in plasma STH occurred after 4 h. All the changes observed after the i.v. administration of endotoxin are dose dependent. Pretreating goats with flurbiprofen completely abolished fever response, as well as the early hyperglycemia and the oxytocin release to i.v. LPS, indicating that these changes were prostaglandin-mediated and might be a reflexion of an activation of the sympathetic adrenomedullary system. The LPS induced changes in plasma cortisol, NEFA and STH are only partly depressed and delayed by flurbiprofen. The residual hormonal responses to high doses of endotoxin suggest that an additional direct action of circulating endotoxins on the hypothalamus cannot be excluded. Intramammary LPS administration in goats only induced a very weak increase in plasma cortisol. The complex interplay of hormones and metabolic substances in the homeostasis of the inflammation reaction is discussed. PMID- 1927029 TI - [Mycoplasma infections of the human genital tract]. AB - It has been shown that genital Mycoplasma may cause local and generalized diseases particular in parturients and premature neonates. For better laboratory diagnosis of Mycoplasma-induced infections, it is necessary to organize the production of culture media and diagnostic kits. PMID- 1927030 TI - [Genital Mycoplasma as a risk factor of obstetric and perinatal pathology]. AB - The paper gives the results of the study into genital Mycoplasma in 1,200 females and 254 newborns and provides strong evidence for the fact that there is a relationship between the Mycoplasma carriage and the inflammatory urogenital processes. It also shows that M. hominis and Ur. urealyticum may persist in the endometrium of females suffering from isthmo-cervical insufficiency. Genital Mycoplasma have been found to play an etiological role in intrauterine infection in premature neonates and in inflammatory processes (endometritis, wound infection following cesarean section) in parturients. PMID- 1927031 TI - [Effect of Mycoplasma infection on the course of pregnancy]. PMID- 1927032 TI - [Detection of Mycoplasma infection in the postpartum period]. AB - The comparative results of microbiological and serological testing of parturients with uneventful and complicated course of the postpartum period were presented. The data justified the etiological role of M. hominis and U. urealyticum in the development of postpartum complications. PMID- 1927034 TI - [Problem of pathogenesis of Mycoplasma infection]. AB - It has been shown that irrespective of the primary focus of affliction, M. hominis-induced infection should be regarded as a systemic disease characterized by an immune-mediated inflammation which is contributed to by blood kallikrein kinin system activation resulting in changes in the coagulative system and fibrinolysis until disseminated intravascular coagulation develops. This allows one to interpret in a new fashion the etiology of some diseases proceeding with signs of vasculitis. PMID- 1927036 TI - [Mycoplasma infections]. PMID- 1927033 TI - [Mycoplasma and Ureaplasma infections in chronic genital inflammatory processes, abortion and infertility]. AB - A total of 43 females including 13 with sterility, 23 with habitual miscarriage and 7 pregnant women with a history of chronic inflammatory diseases were examined by using various tools to detect their Mycoplasma and Ureaplasma infections. The females had been studied for bacterial and chlamydial infections. Forty of them turned out to be infected with M. hominis and U. urealyticum. In some cases, sanation led to the improvement of the patients' status, the occurrence of pregnancy, its favourable course and termination in subjects with sterility and habitual miscarriage. The value of the findings is discussed in the paper. PMID- 1927035 TI - [Social significance of Mycoplasma infections. Prospects of the research]. AB - The paper analyzes the data on the prevalence of human Mycoplasma infections in the USSR and on their diagnostic methods. It also provides evidence for the pathogenicity and biological properties of M. incognitus, a new species, and defines the ways and prospects for further investigations in theoretical and practical Mycoplasma research. PMID- 1927037 TI - [Nonspecific mitogenic factors of Mycoplasma: immunobiological properties]. AB - The readily extractable surface membrane proteins of M. arthritidis and sodium dodecyl sulfate-solubilized membrane components of M. fermentans were found to have the highest mitogenic action on the splenocytes from CBA mice and the least on those from C57BL/6 mice. The M. arthritidis mitogen (MAM) is an antigen dependent T-cell mitogen that inhibits the specific proliferation of T cells, inducing their non-specific proliferation. Dextran sulfate-induced blockage of lymphocyte proliferation under the action of MAM was stimulated with interleukin 2, which suggests MAM-induced expression of receptors to interleukin-2 onto the surface of lymphocytes. A factor that has the activity of interleukin-1 and stimulates the proliferation of C57BL/6 murine thymocytes with phytohemagglutinin was found to liberate into a culture medium. PMID- 1927038 TI - [Interactions between Mycoplasma and macrophages]. AB - Examining the interaction of M. hominis, M. fermentans, and M. arthritidis with peritoneal macrophages of various strain mice has demonstrated that the interaction is related both to the mycoplasma and macrophage types. It has been found that M. arthritidis may multiply and persist for a long time in the macrophages, which is followed by morphological changes developed in the latter and by suppression of phagocytic activity. PMID- 1927039 TI - [Laboratory diagnosis of human Mycoplasma infection]. AB - The paper shows that aggregate hemagglutination reaction, enzyme immunoassays, and passive hemagglutination may be used in the laboratory diagnosis of Mycoplasma-induced infections. In patients with respiratory diseases of unknown origin, the M. pneumoniae antigen is easiest detected in the first days of the disease, then a long-term persistence of antigens as part of circulating immune complexes is frequently seen. An examination of patients with chronic rheumatoid arthritis has indicated that 26.7% exhibit M. arthritidis or M. fermentans antigens, 16.3% display associations of these two types of mycoplasma. The disease in immunocomplex: the mycoplasma antigens circulate as part of immune complexes long in 80%. In females with urogenital abnormality, serum tests have shown U. urealyticum and M. hominis in 83.6%, the patients having inflammatory diseases of unknown etiology. PMID- 1927041 TI - [Contamination of fish tissue cell cultures by Mycoplasma]. AB - The inoculated and primary cell cultures of fish (carp, salmon, and sturgeon) have been studied. Acholeplasma typed as A. laidlawii in terms of its biochemical properties shown in inhibited metabolism has been isolated from 19 samples. The authors consider the source of Acholeplasma-induced contamination of the cell cultures under study. PMID- 1927040 TI - [Laboratory diagnosis of pneumonia caused by Mycoplasma pneumoniae]. AB - The authors demonstrated the possibility to use the technique of counter current immunoelectrophoresis, enzyme immunoassay and passive hemagglutination tests with antibody erythrocytic diagnosticum for the rapid laboratory diagnosis of Mycoplasma infection. The rapid diagnosis of Mycoplasma pneumonias turned to be possible due to the detection of antigen and antibodies to M. pneumoniae in the circulation with the help of counter current immunoelectrophoresis. PMID- 1927042 TI - [Use of monkeys for modeling human Mycoplasma infection]. PMID- 1927044 TI - [Immunogenetic prognosis of the effectiveness of cytostatic therapy of rheumatoid arthritis]. AB - The time course of in vitro cellular immune reactions by using cyclophosphane, prospidin , and methotrexate was examined in 39 patients with rheumatoid arthritis to make predictions of the efficacy of its cytostatic therapy. The agents were evaluated for effects on the expression of Ia-like antigens on the peripheral lymphocytes and synovial fluid of the patients. The optimal doses of the agents for this testing had been chosen in the lymphoid cells from MRL31 lpr mice. The active dosage forms of the cytostatics for the experiment were obtained by administering native agents into the retrobulbar plexus of Balb/c mice, followed by blood isolation of active metabolites . The Ia-like antigen pre expression index which is the ratio of the proportion of Ia-positive lymphocytes in control cultures to that of the cells in the culture after drug addition was used as a marker of the baseline cellular immunity in the patients. The patients having the index more than 1.5 were considered to be sensitive, those with less than 1.5 were insensitive to the drug. Thus, the Ia-like antigen pre-expression index may be used as a predictor in the assessment of the expediency of prospidine use. PMID- 1927043 TI - [Immunobiological characteristics of Mycoplasma hyopneumoniae antigens and the diagnosis of infection caused by this organism]. AB - The paper presents the developed variants of enzyme immunoassay (EIA) using two M. hyopneumoniae (R-14 strain) antigens obtained by biomass freezing and thawing and two Tween-dissolved antigens by gel chromatography. To identify the cultures isolated, an indirect immunofluorescence reaction was proposed by employing agar blocks. The developed methods made it possible to identify 23 bovine-isolated cultures as M. hyopneumoniae antigens. The latter were detected by EIA in diagnostically significant titers in serum and colostrum samples from 2 swine breeding farms. A negative result was obtained in the respiratory mycoplasmosis free farms. PMID- 1927045 TI - [Arthritic pathogenicity of Mycoplasma and Mycoplasma arthritis in humans]. AB - The review deals with Mycoplasma-induced arthritis. It provides the author's own results and the data available in the literature, which suggest that "arthritogenic" Mycoplasma make an etiological contribution to the development of human rheumatic arthritis. It also discusses some well-known and hypothetic mechanisms responsible for the pathogenesis of Mycoplasma-induced arthritis. PMID- 1927046 TI - [Effect of chemically inert perfluororganic compounds (in the form of emulsion) on primary activation of the amplitude of cardiac contractions]. PMID- 1927048 TI - Utilization of cellular transcription factors for adenovirus-induced transcription. PMID- 1927047 TI - [Elaboration of clinico-laboratory criteria of the Mycoplasma variants of rheumatoid arthritis in children]. AB - To develop clinical and laboratory criteria for the differential diagnosis of Mycoplasma-induced arthritides in 78 children with documented rheumatic arthritis (RA), a comprehensive study involving microbiological, immunological, and clinical tools has been performed. Some specific signs of the clinical course of Mycoplasma-induced RA have been defined. However, a differential diagnosis of Mycoplasma-induced arthritis may be made on the basis of a comprehensive study of a patient. PMID- 1927050 TI - Characterization of haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus expressed by a recombinant baculovirus. AB - A recombinant baculovirus containing a cDNA which encodes haemagglutinin neuraminidase (HN) of Newcastle disease virus (NDV) was constructed. Spodoptera frugiperda cells infected with this recombinant virus produced a large amount of HN glycoprotein similar to the authentic HN in size. The recombinant HN glycoprotein was localized on the surface of the infected cells and conserved its haemadsorption and neuraminidase activities. The antigenic properties of the recombinant HN glycoprotein seemed to be slightly different from the authentic one, as judging by the reactivity with a panel of monoclonal antibodies specific to the antigenic sites responsible for neutralization of viral infectivity. Chickens inoculated with the cells infected with the recombinant virus developed haemagglutination-inhibition and virus neutralization antibodies, and were completely protected from the NDV challenge. PMID- 1927049 TI - Decreased replication capacity of a duck hepatitis B virus mutant with altered distal pre-S region. AB - We have observed in a previous study that insertion, deletion and partial frameshift mutation in the distal pre-S region did not abolish replication capacity of the duck hepatitis B virus (DHBV) (Li et al., 1989, J. Virol. 63, 4965-4968). To compare further the relative replication capacity between the pre S mutant and wild type virus, ducts were infected with either the wild type DHBV strain or a pre-S mutant (FS-17) characterized by a total change of nine consecutive amino acid codons in the distal pre-S region. Compared with the wild type virus, FS-17 exhibited decreased replication capacity whether in separate or mixed infection. The decreased viral replication was correlated with delayed appearance of supercoiled DNA and viral RNA in the hepatocytes. Besides, FS-17 induced persistent viremia when inoculated into 1-day-old ducklings; hence the transient viremia which had been observed in the previous study was probably due to the time delay needed to generate compensatory deletion mutation. PMID- 1927051 TI - [Isolation and characterization of colloidal soluble polysaccharides in raspberry juice]. AB - Depending on the preparation method, the colloid content of raspberry juices treated with pectolytic enzymes, can be up to 2.5 g/L. Analysis of the polysaccharides shows that there are in particular, arabinans, arabinogalactans type II and rhamnogalacturonans. While the content of arabinans could be reduced by the action of arabinases, the arabinogalactans and rhamnogalacturonans were not degraded by conventional pectic enzymes. Besides these cell-wall polysaccharides, it was possible to isolate a high molecular-mass beta-glucan, which is thought to originate from Botrytis cinerea. Technical problems in juice clarification or filtration may be caused by this beta-glucan or the high content of residual pectic substances. PMID- 1927052 TI - [Prevalence of psychotropic and anti-epileptic drug use in mentally handicapped students]. AB - Treatment with psychotropic and anticonvulsant drugs was examined in students attending special schools for the mentally retarded in Hamburg (n = 459). Psychotropic drugs were taken by 2.8% and anticonvulsant drugs by 16.3%. Medication did not vary by age or sex. These results are discussed with regard both to the results of other research done with mentally retarded students and to representative samples of children and adolescents in the Federal Republic of Germany. PMID- 1927053 TI - [Determinants and educational approaches to AIDS anxiety in adolescents]. AB - On the basis of a questionnaire filled out by 480 adolescents determinants of fear of AIDS were evaluated with a model of linear structural equations. The main factors that appeared were knowledge about AIDS (those who know more report less fear), personal involvement (those who are confronted more with the problem of AIDS report more fear) and sexual experience (those who are sexually more experienced report less fear). The last finding is interpreted to the effect that mainly sexually inexperienced adolescents, who are usually also the younger ones, shift their sexual fears to the AIDS-complex. PMID- 1927054 TI - [Psychiatric and neuropsychological symptoms in children with arachnoid cysts--a case report]. AB - Arachnoid cysts (AC) are intracranial, extracerebral cysts. They can produce a wide variety of neurological symptoms, but they can also be asymptomatic or produce psychological or psychiatric symptoms. First, a short overview of the clinical manifestations of AC is given. There is an astonishing lack of literature dealing with psychological problems in children with AC. The case of a 12-year-old boy with a large left temporofrontal AC without increased intracranial pressure is presented. The psychiatric symptoms, which had begun only a few months earlier, included lack of interest, attention deficit, difficulties in contact and communication, severe outbursts of aggression and obsessive-compulsive, inhibited behavior. The main neuropsychological finding was slow and hesitant expression of thoughts despite an intelligence level in the upper normal range. The findings and course are described in detail. They are discussed as signs of an organic psychosyndrome due to the AC. PMID- 1927055 TI - [Predictors of outcome in instrumental behavior therapy of enuresis]. PMID- 1927056 TI - [Significance of parent-child relations for development of moral reasoning in adolescence: a study of psychiatrically disordered adolescents]. AB - In accordance with structural-developmental theory in the tradition of Piaget and Kohlberg, moderate amounts of conflict between adolescents and their parents should influence the sociomoral development of the adolescents in an optimal way. The same hypothesis is compatible with a social-constructivistic approach (Youniss, Keller, Haan, Miller), which emphasizes the role of communicative processes in the development and validation of moral rules. The results of our empirical study with 43 severely mentally disturbed adolescents aged 14 to 19 years indirectly confirm this hypothesis. Adolescents with moderate amounts of family conflict reached a higher stage in moral reasoning than those with either very severe problems or only minor problems with their parents. In an additional analysis we investigated the relation between the severity of the conflicts and the emotional attachment of the adolescent to his or her parents. Our data indicate that moderate problems in the interaction between child and parents are associated with a family atmosphere that seems to facilitate the development of an integrated personality and identity. A balanced coexistence of separateness and connectedness offers the young person the best chance to develop and clearly communicate his or her own point of view and to solve interpersonal problems by reaching a consensus that takes into account the needs and interests of the other family members. PMID- 1927057 TI - [Recent advances in neuropsychopharmacology of the central histaminergic neuron system]. AB - Recent immunohistochemical studies have shown the distribution of histaminergic neurons in the mammalian brain, which are concentrated in the tuberomammillary nucleus of the posterior hypothalamus and project efferent fibers to almost all parts of the brain from the olfactory bulb to the spinal cord. Histaminergic neurons co-express other neuroactive substances, such as gamma-aminobutyric acid, adenosine, substance P, galanin and Met-enkephalin-Arg-Phe. In addition, pharmacological studies have demonstrated the presence of presynaptic histamine H3-receptors (autoreceptor) in addition to H1- and H2-receptors. The specific agonist (alpha-methylhistamine) and antagonist (thioperamide) of H3-receptors were developed. Results from a number of studies indicate a variety of physiological roles of neuronal histamine such as thermoregulation, feeding behavior, sexual activity, sleep-wakefulness cycle, hormonal regulation and so on. Moreover, histaminergic drugs affect not only the emotional behavior, but also are effective to treat some patients of depression, Parkinson's disease, akathisia, motion sickness and so on. The central histaminergic neuron system is also affected by mental disorders and neuropsychopharmacological drugs. This review especially focused on these points and suggests that the central histaminergic neuron system may play an important role in the regulation of mental functions. PMID- 1927058 TI - Effects of repeated administration of buprenorphine on ambulatory activity in mice. AB - Effects of repeated administration of buprenorphine, given 5 times at intervals of 3-4 days, were investigated by ambulatory activity in mice. Buprenorphine (0.3 and 1 mg/kg sc) significantly increased the activity, and tolerance to the effect tended to be produced during the repeated administration schedule. The mice that experienced the repeated administration of buprenorphine exhibited an increased sensitivity to the ambulation-increasing effect of methamphetamine (2 mg/kg) in parallel with the doses of buprenorphine. However, no significant modification of the sensitivity to buprenorphine was produced in the mice that had experienced the repeated methamphetamine administration. Furthermore, the established reverse tolerance to methamphetamine was not significantly modified by the repeated treatment with buprenorphine (0.1, 0.3 and 1 mg/kg). PMID- 1927059 TI - [Cholinergic modulation on stereotyped behavior and behavioral hypersensitivity (reverse tolerance) in rats]. AB - The failure in the mutual balance between striatal/mesolimbic dopaminergic neurons and the inhibitory system, and a decreased activity of mesocortical dopaminergic neurons may account for biological base of paranoid schizophrenia. We tested this hypothesis by investigating stereotyped behavior and "reverse tolerance" in dopaminergic supersensitivity co-existing with a low-level activity of the inhibitory cholinergic system induced by the chronic administration of methamphetamine (MAP) 4 mg/kg in combination with scopolamine (SCOP) 0.5 mg/kg, in male Wistar rats. For investigating the influence of mesocortical dopaminergic neurons, experiments were designed to compare these behavioral responses in isolated rats, in which the activity of mesocortical dopaminergic neurons seemed to be reduced, to those in group-housed rats. The treatment with MAP plus SCOP produced significantly more potent effect in enhancing stereotyped behavior and "reverse tolerance" than the treatment with MAP only. Stereotyped behavior and "reverse tolerance" induced by the MAP plus SCOP treatment were more intense in isolated rats than in grouped rats. Effects of haloperidol (1 mg/kg) and pimozide (2 mg/kg or 5 mg/kg) on stereotyped behavior were less in MAP plus SCOP treated rats and isolated rats. The data may support a working hypothesis. PMID- 1927060 TI - Biochemical markers of bone metabolism. AB - Bone metabolic homeostasis is regulated by a number of hormones and local modulators, and the study of these factors has been of major help in our understanding of bone disease. However, these parameters do not, in a strict sense reflect the metabolic and biochemical changes in the diseased bone tissue. Thus, there is a great interest in the study of biochemical specific "markers" of bone metabolic processes, namely of bone formation and bone resorption. Alkaline phosphatase, osteocalcin, osteonectin, and procollagen type I propeptides are the currently known markers of bone formation, whereas urinary hydroxyproline and hydroxylysine glycosides, plasma tartrate resistant acid phosphatase, and urinary hydroxy-pyridinium crosslinks of collagen are considered markers of bone resorption. In this paper, we review the background work on each of these markers, and subsequently give an overview of the currently available data on their usefulness in metabolic bone diseases, namely in Paget's disease of bone, primary hyperparathyroidism, osteoporosis, and renal osteodystrophy. PMID- 1927061 TI - [Rheumatologic and radiologic symptoms of dialysis-associated beta 2 microglobulin amyloidosis: long-term retrospective study of 175 chronic hemodialysis patients]. AB - beta 2-microglobulin amyloidosis is a major complication in chronic hemodialysis patients. Destructive arthropathy, spondylarthropathy, and carpal tunnel syndrome are clinical manifestations of beta 2M amyloid depositions within the joints, intervertebral discs, and tendon sheets. We have investigated the prevalence of beta 2M amyloidosis associated radiological joint lesions in a population of 175 patients on chronic hemodialysis. In 32 of 175 patients the diagnosis of amyloidosis arthropathy and spondylarthropathy was made by radiomorphological criteria. These 32 patients were asked about rheumatic symptoms (localisation and character of pain, synovitis, carpal tunnel syndrome, influence of dialysis membrane on pain) and examined clinically. Bilateral pain of the shoulders or wrists was complained by most of the patients. 24 of the 32 patients had signs of secondary hyperparathyroidism besides beta 2M-amyloidosis. 29 patients had a carpal tunnel syndrome, 23 of whom had to be operated. beta 2M-amyloid was histochemically demonstrated in all of these 23 cases. Renal transplantation led to immediate pain relief in 3 out of 3 patients, a change of the dialysis membrane (high-flux membrane) improved chronic pain in the majority of patients. PMID- 1927062 TI - Serum lipid pattern and apolipoproteins (A1 and B100) in active rheumatoid arthritis. AB - Cardiovascular diseases and atherosclerotic manifestations have been reported to be the most common causes of death in rheumatoid arthritis (RA). In the present investigation the levels of serum lipids, apolipoproteins (A1 and B100), total proteins, and albumin were studied in 35 female patients affected by active RA. Apolipoproteins A1 and B100 were significantly lower in RA patients than in controls. No significant difference was observed in total cholesterol, LDL cholesterol, or triglycerides. In contrast, HDL cholesterol and serum albumin were significantly lower in RA patients compared to controls. The finding of reduced apolipoproteins and HDL-cholesterol levels may represent an important factor in the etiology of cardiovascular and atherosclerotic disease in RA. Reduced levels of albumin in active RA may indicate a reduced rate of proteins like lipoproteins in the liver. PMID- 1927063 TI - Contribution to the study of tetracycline bone side-effects. Absence of calcium deposition impairment in the trabecular bone of a patient treated during 3.5 years with doxycycline. AB - Tetracyclines are easily incorporated into bone; whether bone formation is impaired during this process is still a matter of debate. We therefore studied, by histomorphometry, fluorescence microscopy, and microradiography, a sample of trabecular bone from a patient with a total hip arthroplasty, treated without interruption for 3.5 years with doxycycline because of a pertrochanteric abscess. Absence of osteomalacia and a low-mineralization score of the edges of the trabeculae similar to that observed in a control group of 12 subjects suggest no interference by doxycycline with calcium deposition in bone. PMID- 1927064 TI - [Therapy of non-steroidal antirheumatic drug-induced gastrointestinal lesions with misoprostol]. AB - In a multicenter placebo-controlled double-blind study in patients with degenerative or inflammatory rheumatic diseases the prostaglandin analogue misoprostol, in a dose of 200 micrograms twice daily after meals, was administered for the treatment of NSAID-induced lesions and symptoms of the upper gastrointestinal tract. Treatment with an NSAID was continued. Misoprostol treatment was demonstrated to be clearly superior to placebo in respect of reduction of gastroduodenal lesions and gastrointestinal pain. In addition, the physician's global assessment of gastrointestinal complaints was also statistically significantly better. No difference between the groups was found with respect to antirheumatic action of the NSAIDs. PMID- 1927065 TI - [Spondylodiscitis as a dominant early symptom of juvenile ankylosing spondylitis]. AB - A 12-year-old female (HLA-B27 negative) presented with unilateral low back pain and sterno-clavicular arthritis. Six months after onset the clinical and radiological findings determined spondylodiscitis L1/2. On the basis of the clinical findings (oligoarthritis, symptomatic sacroilitis, spondylodiscitis), juvenile ankylosing spondylitis was suspected. The diagnosis was corroborated 18 months after the first occurrence of symptoms by the appearance of typical changes in the sacroiliac joint that are indicative of juvenile ankylosing spondylitis. Because of persisting antibodies against Borrelia burgdorferi, the possibility of B. burgdorferi-induced reactive arthritis with involvement of the axial division of the skeletal system was considered. After 3.5 years of observation the condition showed a benign course with radiologically observable consolidation of the spondylodiscitis. To our knowledge, this is the second case described of juvenile ankylosing spondylitis with spondylodiscitis as a dominating feature. PMID- 1927066 TI - [Comment on the publication by J. Graf, L. Bernd, R. Pauschert and F. U. Niethard: "The special case: rare occurrence of villonodular synovitis in both shoulder joints"]. PMID- 1927067 TI - [Comments on the fascination with "anorexia nervosa"]. PMID- 1927068 TI - [Therapy of patients with severe anorexia (summary of a report on a research project)]. AB - From 1981 to 1983 a special project on anorexia nervosa was granted within "Sonderforschungsbereich 115" (Hamburg--West Germany). We want to give a review of those aspects of our studies which led us to a therapeutic concept for severely affected inpatients. Starting in the diagnostic field with problems of motivation and alexithymia we turn to psychodynamic subgroups, mention the studies of endocrinology, the Self-structure and the father-types, continue with epidemiologic studies as a device of interpreting pathologic phenomena. Concerning our therapeutic investigations--basing on a long-term follow-up--we report on therapeutic elements, results, follow-up and a hierarchy in prognostic factors of our in-patient treatment. In a critical survey of the results we finally discuss therapeutic recommendations. PMID- 1927069 TI - [Limits of psychotherapeutic effectiveness in anorectic patients]. AB - Catamnestic studies of psychotherapeutically treated anorectic patients show that the pathological attitudes and convictions regarding food, eating habits and body weight persist regardless of whether the treatment was successful or not. Reasons for the persistence of these patterns of attitudes and behavior have not been able to be clarified up to now. The pathological attitudes of anorectic patients towards food, eating and body weight are closely associated with a high narcissistic profit. These patterns of convictions and attitudes fulfil the function of a stable resistance against deeper anxieties and also wishes and needs which are perceived as being threatening; therefore these patterns will survive as long as the level of the resisted wishes and needs remains concealed. During the treatment process they have to be made sizeable as interaction dynamics in order to be accessible for changes. Two characteristic aspects of interaction dynamics are discussed here. PMID- 1927070 TI - [The psychodynamics of syndrome changes after forced healing. A case vignette exemplifying a case of anorexia nervosa]. AB - The case vignette at hand depicts the syndrome shift from puberty anorexia nervosa to a conversion syndrome (localized pain syndrome). The development conditions are described and treatment-technical implications named. The author discusses under psychoanalytical viewpoint in how far the symptom shift goes along with a structural change from a lower to a higher developmental level, whereby this is viewed under the causes which influence the disease process. PMID- 1927071 TI - [Genetic determinants in anorexia nervosa. Results of twin studies]. AB - Contrary to many widely discussed theories of anorexia nervosa the conclusive human genetic results of research with twins have been almost totally ignored and individual casuistry has often been misinterpreted. The two twin-series studies at hand (Crisp et al./London and the author)--totally independent of each other and compiled during the same time period--speak unmistakably for a great genetic determination and genesis of anorexia nervosa. The AN-twin pairs compiled by the author over a period of 30 years are described here. PMID- 1927072 TI - [Social integration of patients with anorexia nervosa and bulimia]. AB - The current study investigated the psychological and social problems of 46 patients with anorexia nervosa and 34 patients with bulimia who met the DSM III criteria. Data were compared with 50 normal controls, using the "Fragebogen zur Sozialen Integration" (FSI, a German translation of the social adjustment scale self report) and the Freiburger Personlichkeitsinventar (FPI, a German personality questionnaire). Women with anorexia nervosa as well as patients with bulimia demonstrated a significant impairment in all areas of social relationships, while there were no differences between these patient groups. On the FPI, both groups reported significantly more depressed, feelings of being nervous, neuroticism and femininity, less sociable and calm than the controls. PMID- 1927073 TI - [Some critical considerations on the status of the psychoanalytic discussion of bulimia]. AB - The most discussed psychoanalytic publications about bulimia and their central thesis are critically reported. Apparent is the accent of the very early childhood development, especially the earliest stages of mother-child-symbiosis in their pathogenic influence. Only some authors oppose with regard to conflicts of later stages of development in bulimic women. Personal clinical experiences and research data support the critique of the exclusive accent of early development. Rather adolescent developmental problems and particularities of female adolescence are stressed by the author. PMID- 1927074 TI - [Resolved promotional contributions in the area of psychosomatic medicine, psychotherapy and psychoanalysis]. PMID- 1927075 TI - [Can resorbable suture material be used in surgery of the supra-aortic branches?]. AB - The experience with the use of monofilament absorbable suture (5/0 USP) in supraaortal vessels shows the same results related to neurological complication. The postoperative technical complications (bleeding, occlusion, restenosis) could be significantly reduced (p less than or equal to 0.05). Suture ruptures of aneurysms were not observed after resorbable vascular suture. The resorbable monofilament suture material is useful in high pressure vessel system. PMID- 1927076 TI - [Vascular stenosis of the branches of the aortic arch. Surgical treatment and long-term follow-up]. AB - Since 1971 69 patients have been operated on for lesions of branches of the aortic arch (71 surgical procedures). In 80% of the patients extrathoracic reconstructions were performed, mainly carotid-subclavian bypasses (64%) using knitted dacron grafts (6 mm and 8 mm diameter). A transthoracic approach was used in 20% of the patients. No patient died after operation and no ischemic neurological deficit occurred. The cumulative survival rate was 89% after five and 59% after ten years. The cumulative patency rate in the survivors was 100% after transthoracic approach after five and ten years. Identical patency rates were observed after extrathoracic carotid-subclavian bypass using 8 mm dacron grafts, whereas in 6 mm grafts the patency rate was only 67% after five and ten years. 85% of all patients were symptom-free and additional 10% improved. These results confirm that carotid-subclavian bypass using 8 mm dacron grafts has a long term patency rate identical to those after anatomical transthoracic procedures. PMID- 1927077 TI - [Intraoperative complications in interventions on peripheral arterial vessels]. AB - Between 1980 and 1989, 2395 reconstructive operations were performed for peripheral arterial occlusive disease on vessels above the aortic arch and below diaphragm. 543 (22.6%) procedures of these represented operations upon the supraaortic branches, 756 (13.5%) were operations upon the abdominal aorta and pelvic vessels, 647 (27.0%) were performed on the upper and lower extremity and 449 (18.7%) miscellaneous like e.g. arterial embolectomies, venous embolectomies and others. Intraoperative complications occurred in 2.8% where as there was a 3 fold postoperative complication rate (9.1%). Diffuse bleeding contributed the highest rate of complications followed by injuries different organs. In most cases injuries to the spleen resulted from undue retraction. Other complications were iatrogenic lesions of the ureter, neural injuries and intraoperative bypass occlusions. PMID- 1927078 TI - [Complications after percutaneous transluminal angioplasty and vascular surgery]. AB - Percutaneous transluminal angioplasty (PTA) is an accepted technique in the treatment of occlusive vascular disease. We report complications associated with balloon catheter dilatation and their treatment in the period from 1. 1. 1986 to 31. 3. 1990. Complications were found at the site of dilatation and the site of insertion of the catheter, mostly in the pelvic and femoral region. Surgical correction was successful in all patients, however three patients died postoperatively of acute myocardial ischemia. To avoid these complications close co-operation between the radiologist performing the dilatation and the vascular surgeon managing the complications should be assured. PMID- 1927079 TI - [Perioperative complications in pacemaker surgeries]. AB - In the years 1979 to 1985 (period I) 717 (102 per annum), in 1986 to 1989 (period II) 295 (73 per annum) pacemaker procedures had been performed at the cardiothoracic surgery division of Wurzburg University. Indications for pacemaker therapy were in 35.4% vs. 36.6% (period I vs. period II) an atrioventricular block grade II or III, in 18.1% vs. 26.4% sick sinus syndrome, in 15.3% vs. 18.0% bradycardic rhythm disturbances, in 9.5% vs. 6.1% a sinuatrial block, in 6.5% vs. 2.4% a bradycardic sinus rhythm, in 12.4% vs. 3.7% others. While 41% of the procedures were performed under general anesthesia during the first period of observation, local anesthesia was predominant later on. Preferred venous access (79% vs. 74%) was the right cephalic vein followed by the subclavian vein (12% vs. 14%). The amount of the two chamber systems rose form 11% (period I) to 24% (period II). Intraoperative complications occurred in 2.5% vs. 5.8% and postoperative (within 14 days) complications occurred in 4% vs. 5.8%, respectively. No death was to be registered. The reasons for the increase of intra- and postoperative complications are discussed. PMID- 1927080 TI - [Advantages of the combination of surgical and sclerosing treatment of varicose veins. A new kind of therapy for varicose veins]. AB - In many patients with varicose veins the combination of surgery and sclerotherapy gives good results and reduces the operating time for each patient considerably. Especially in all patients with recurrent and side branch varicose veins this method seems to be advantageous. During the last ten years we treated 3328 patients with varicose veins. The combined method was used in 64% (2130 patients). PMID- 1927081 TI - [Experimental development of carcinoma in rats caused by N-nitrosopiperidine with vitamin C]. AB - In animal experiments with Wistar rats we attempted to determine if oral application of Vitamin C inhibits or delays carcinogenesis due to oral administered N-Nitrosopiperidine (NTP). One group of animals received NTP only, two other groups NTP and Vitamin C either alternating or simultaneously. A fourth group receiving only Vitamin C served as control. Carcinomas of the esophagus, stomach and liver developed in response to NTP application. The additional administration of Vitamin C neither inhibited nor delayed the development of carcinomas. PMID- 1927082 TI - [Temporary stoma in infancy and childhood]. AB - Between 1979 and 1989 70 colostomies and ileostomies were performed in children at the University Clinic of Freiburg. 56 of them could be closed in the same period. Indications for the stoma were an acute abdomen in 37%, atresia in 26% and M. Hirschsprung in 21%. 79% of the stomata were performed in the first year of life. The most serious complications were prolapse, stenosis and retraction. 17% of the stoma complications required an operative treatment. PMID- 1927084 TI - [Pedicle torsion, hemorrhagic ovarian infarct. A rare cause of pediatric acute abdomen]. AB - The most common cause of acute abdomen in a child is acute appendicitis followed by mesenteric lymphadenitis, invagination, strangulation-ileus as a result of volvulus and more rarely perforated Meckel's diverticulum. However even with a child, from a differential diagnosis' aspect, a gynaecological cause should be taken in account too. From time to time one comes across a polycystic-alterated, with twisted lig. ovarii, haemorrhagic and infarctioned ovary without any endocrinological or other pathological irregularities which produces these complaints and symptoms. In the following casuistic such an instance is described. PMID- 1927083 TI - [Ovarian cyst. A predisposing factor for ileus in the neonatal period and early infancy]. AB - Cystic and solid tumors of the ovary are rare during the new born period and infancy and usually become clinically apparent only during childhood adolescence. Any cystic ovarian enlargement is almost always benign but can cause signs of an acute abdomen because torsion of the ovarian cyst can lead to small bowel obstruction. This may be the first clinical sign of the cyst if it had not yet been detected by prenatal or postnatal ultrasonography. On the basis of our own observations and a review of the literature it appears that ovarian cysts predispose to mechanical small bowel obstruction in new borns and infants. PMID- 1927086 TI - [Urethral replacement with free urinary bladder mucosal transplant]. AB - An electro-resection was carried out in a subvesical blind-hole stenosis in a 5 month old male baby. Afterwards a 3 cm long urethral defect resulted in the penoscrotal junction. This was bridged with a free mucosal graft from the urinary bladder by the technique of Memmelaar and Hendren. PMID- 1927085 TI - [Post-traumatic hemobilia in childhood]. AB - We observed three patients with a hemobilia after surgically or conservatively treated liver lacerations. The diagnosis was suspected on clinical grounds and verified by ultrasonography, computed tomography or angiography or a combination thereof. Depending on the findings therapy was planned reaching from conservative treatment to liver resection. Because this complication is rare it should be cared for in a specialized institution. PMID- 1927087 TI - [Our surgical heritage. Eugen Hahn. 1841-1902]. PMID- 1927088 TI - [Hiatal hernia. Symptoms, diagnosis and therapy]. AB - Forty-eight patients with a mean age of 53 years were treated for hiatal hernia at the University of Wurzburg Department of Surgery between 1983 and 1989. The cohort was subdivided according to type of herniation, age and sex, and symptoms. Conservative treatment sufficed in 22%, but the majority (78%) underwent surgery. Nissen's fundoplication predominated (48%); other methods used were gastropexy (17%), antrectomy with Roux's Y-gastrojejunostomy (6%) and Angelchik's prosthesis (6%). Intra- and postoperative complications included 5 splenectomies following iatrogenic trauma to the spleen, 2 cases of subphrenic abscess, and 2 with pleural effusions. The extensive discussion stresses the various operative treatment procedures and their respective advantages and drawbacks. PMID- 1927089 TI - [Long-term follow-up of patients surgically treated for para-esophageal and mixed hiatal hernias. Experiences with more than 100 surgical patients]. AB - During the years from 1948-1990, we operated on 112 patients with paraesophageal and mixed hiatal hernias. One hundred patients who had been operated up to the year 1988 were followed up over a long period. Preoperatively, gastroesophageal reflux occurred in 52%, hemorrhage in 18%, riding ulcer in 7%, and incarceration and obstruction in 9%. Up to the beginning of the seventies, hiatoraphy and gastropexy were carried out. In these patients, the checking showed the occurrence of the relapse of hernias in 47%, reflux in 43% and subjective complaints in 26%. This finding induced us to change the surgical procedure and, in the following years, we performed hiatorhaphy, fundoplicato, fundophrenopexy and anterior gastropexy. The checking showed a decrease in the occurrence of the relapse of hernias to 21%, gastroesophageal reflux to 9% and subjective complaints to 10%. The period of the follow-up ranged from 1 to 19 years. The operative letality was 3%. PMID- 1927091 TI - [Thovara inguinal hernia operation. Results of follow-up in adults]. AB - A new procedure for inguinal hernia operations is described: the Thovara method, which is really a modified version of the plastic technique by Bassini-Kirschner Lichtenstein. From 1985-1986 167 patients were operated on for inguinal hernia in our University Hospital, using this hernia plastic technique with a tension-free mesh. Though the rate of early complications is good, we should mention that there were 19 cases of testicle swelling. The number of early and late recurrences were very low: 2 cases (1.2%). Hospitalization averaged from 2 to 4 days. The procedure is easy to perform and almost painless. PMID- 1927090 TI - [Controlled study of cremaster resection in Shouldice repair of primary inguinal hernia]. AB - 237 Shouldice operations with resection of the cremaster muscle from the Department of Surgery of the RWT University of Aachen were compared with 153 Shouldice repairs without resection of the cremaster muscle from the Department of Surgery of the Elizabeth Hospital in Essen. The aim of this prospective controlled trial was to determine the value of the resection of the cremaster muscle in Shouldice's hernia repair. A comparable follow-up of 12 to 26 months in both groups revealed no significant differences in early-postoperative complications. In the group without resection of the cremaster muscle the incidence of chronic inguinal pain was reduced. However, avoidance of the cremaster resection is not advisable because it leads to atypical indirect recurrences and totally higher recurrence rate (2.6%), so four indirect recurrent hernias were diagnosed. In the group with resection of the cremaster muscle no indirect recurrent hernia was detected, only one direct recurrent hernia was documentated. The significantly elevated rate of recurrent hernias (p less than 0.05) and the occurrence of atypical indirect recurrent hernias in the group without resection of the cremaster muscle demonstrates the important influence on the technique of repair. Based on our results the resection of the cremaster muscle is an essential part of Shouldice's hernia repair. PMID- 1927092 TI - [Treatment of iatrogenic esophageal perforation]. AB - Between the years 1985 and 1989 11 patients with iatrogenic esophageal perforation were treated at the Department of Surgery at the University of Wurzburg. 5 perforations were diagnosed within 24 hours, the others after 1 to 5 days. All patients received a non resective surgical treatment, consisting of excision of the perforated area, primary closure in single suture technique strictly extramucosal and drainage. In addition fibrin glue and a pleural wrap protected the suture. In 55% the postoperative course was completely inconspicuous. Only one patient with a recidive of a gastric cancer with lung and liver metastases, died 11 days after operation of a cervical perforation. PMID- 1927093 TI - [Para-duodenal hernia. A rare cause of high small intestine ileus]. PMID- 1927094 TI - [Incidence of ulcer disease among patients of the Detmold Surgical Clinic 1949 1989]. AB - Between 1949 and 1989 2,042 patients with peptic ulcer disease were treated operatively. The incidence of operations increased markedly after 1949, reached a summit from 1964 to 1978, and decreased thereafter steadily. Different from this trend there was a continuous rise in operations for peptic ulcers in women since 1949 in particular in ulcus perforations. Moreover it could be demonstrated that the need for surgery because of severe complications of ulcus disease effects mainly elderly patients. PMID- 1927096 TI - [Transanal decompression procedure in acute pseudo-obstruction of the colon]. AB - Based on 3 observations the relatively rare pseudo-obstruction of the colon is described. The pathophysiological mechanism is still unknown. In chronic or subacute cases a conservative treatment seems to be justified. However this does not apply to advanced cases or when there is threat of a colon perforation. As a possible alternative to a colostomy for transanal aseptic decompression a new intestinal tube is introduced. PMID- 1927095 TI - [Possibilities for reconstructing the insufficient anal sphincter and assessment of results by anorectal stress profile]. AB - It is reported about diagnostic and operative techniques as well as late results based on 95 own operations in anal incontinence. Main points are sphincter repair, gracilis plastic, levator sling procedure and the results based on anorectal manometry. Anamnestic score and manometric dates were correlated and are comparable. PMID- 1927097 TI - [Incidence, prevention and therapy of ureteral injury in colorectal surgery]. AB - Injury of the ureter means a rare intraoperative complication in colorectal surgery. In the patient clientele of the Department of Surgery of the Technical University Munich this type of injury was found only in 4 patients out of 805 colorectal procedures (0.54%). PMID- 1927098 TI - [Errors in lavage therapy in diffuse peritonitis]. AB - The suppurative peritonitis is still one of the major clinical concerns for surgeons in these days. The presence of bacteria and endotoxins within the peritoneal cavity activate a chain of reactions, which mostly are still unknown, but frequently determinate the course of the disease. Because of the multifactorial system of the biochemical processes, we are coming to the paint to ask for a final chemical reaction of all these processes. The final reaction in this high toxic systems is taken place in an acidic pH range. Our experiments show, that the intraperitoneal alcalisation by lifting up the pH in the physiological range or even higher produces a stop in the septical reactions. Consequently because of these results we changed our treatment for severe peritonitis as followed: 1. Focus sanitation: Consequent treatment for the underlying cause of infection. 2. Continuous abdominal lavage over 4 catheters in each of the quadrants of the abdominal cavity with 101 of saline solution together with 8.4% Na-bicarbonate up to a pH-range of 7.6. 3. First revision of abdomen after 12 h after removing the catheters the normal intraoperative lavage with 10-15 1 saline solution with 8,5% Na-bicarbonate is performed. 4. The abdomen remains open and daily revisions and lavage with Na-bicarbonate are performed. 5. Early clinical data support the experimental findings. PMID- 1927099 TI - [Continuous intestinal suture with polydioxanone]. AB - Within five years a total of 264 anastomoses were performed on 241 patients in a continuous extramucosal single-layer end-on suture technique with polydioxanone. In 133 small bowel, and 131 colonic anastomoses there were no leakages as the only complications attributable to the procedure. Both anastomotic failures occurred after colonic resections, for a 1.5% dehiscence rate. Small bowel anastomoses healed without complications. PMID- 1927100 TI - [Our surgical heritage. Surgical infections once and now. Progress in asepsis 100 years ago]. PMID- 1927101 TI - [New therapy recommendations in oncology]. PMID- 1927103 TI - [Oocyte removal in conjunction with pelvic microsurgery]. AB - The paper evaluates results of gamete transfer into the oviduct or embryos into the uterus in connection with pelvic microsurgery. Between August 1981-December 1989 225 microsurgical operations have been performed in a stimulated cycle. Ovaries have been stimulated by clomiphene-citrate or in combination with human menopausal gonadotropin. The operation was timed 34 hours after application of human chorionic gonadotropin. In a group of 156 women we recovered at least one oocyte. From 77 gamete transfers into the oviduct we achieved 11 pregnancies, i.e. 14.3 per cent. 46 embryo transfers into the uterus resulted in 5 pregnancies, i.e. 10.9 per cent. From the total number of 16 pregnancies we achieved 5 deliveries, 8 clinic abortions and 3 ectopic pregnancies. The connection of sterility microsurgery with oocyte retrieval increases the success rate of operations without another stress of a patient and has also its economic significance. PMID- 1927102 TI - [Development and results of microsurgical sterility operations at the Gynecology and Obstetrics Clinics of the Brno Masaryk University]. AB - Four periods of microsurgery of tubal sterility and present approach to individual operation techniques in respect to assisted reproduction are evaluated. The evaluation concerns 240 operated women, their average was 31.8 years, 68.8 per cent women were operated for the first time. The pregnancy rate arrived at 90 pregnancies (40.8 per cent), 80 women delivered (33.3 per cent), the abortion occurred in 7 cases (2.9 per cent) and ectopic pregnancies occurred in 11 cases (4.6 per cent). By adhesiolysis we achieved 56 per cent pregnancies, by fimbrioplastics 34 per cent pregnancies and by neostomies only 27 per cent pregnancies. Tubal anastomosis (11 operations) and tubal implantations (9 operations) had no significant influence upon evaluation. Deflection from tubal implantations, anastomoses (except refertilizing ones) or neostomies (especially iterative ones) in favour of in-vitro-fertilization is evident. PMID- 1927104 TI - [Combined treatment with a GnRH-analog and gonadotropins in IVF-ET/GIFT patients after previously unsuccessful pure HMG stimulation]. AB - Clinical results of a combined GnRH-analogue (buserelin, long protocol) + HMG stimulation of 44 IVF-ET or GIFT patients with previously failed pure HMG stimulation have been analysed. The cancellation rate and the incidence of premature LH surge was found to be lower in the buserelin + HMG group than in the control HMG group (30% vs. 40% and 16% vs. 51%). There was no significant difference between the buserelin + HMG and the control HMG group, neither in the number of retrieved and fertilized oocytes and transferred embryos nor in the fertilization and pregnancy rate. The combined GnRH-analogue and gonadotropin therapy led to a decrease of the cancellation rate and of premature LH surge in patients with previously failed pure HMG stimulation. In this group of patients the use of buserelin leads to treatment results comparable to results of pure HMG stimulated patients without previously failed stimulation cycles. Thus the GnRH analogue + HMG stimulation is recommended for patients with previously unsuccessful pure HMG stimulation. PMID- 1927105 TI - [Possibilities for optimizing radiotherapy of cervix cancers by measuring the enzyme peak of GPI after initial irradiation]. AB - Following the first irradiation with a dose of 1.6 respectively 2 Gy we determined the activity of glucose-6-phosphate isomerase (GPI) and of creatine kinase in intervals of 30 minutes for 24 hours. In all patients we could observe peaks of GPI-activity 15.5 to 19.5 hours after irradiation corresponding to tumour volume and grading. Frequency depends on present lymph node metastases detected by lymphography and/or computed tomography. Possible reasons have been discussed by the viewpoint of radiation biology and the meaning with respect to an optimal radiation treatment. PMID- 1927106 TI - [Obstetric management and results of premature amniotic rupture]. AB - Out of 6957 deliveries of the years 1987 and 1988 (7.2%) pregnant women have been analysed because premature rupture of fetal membranes. In 23.4 per cent symptoms of amniotic infection could be observed. In 31 per cent pathogenic germs could be identified from cervical swabs. In 33.6 per cent gestational period could be prolonged from 2 to 7 days, in 4.2 per cent more than 7 days. We found upon 32nd week of pregnancy a significant reduction of respiratory adaptation disturbances of 22%. Neonatal sepsis had been found at 50% till completion of 32nd week of pregnancy. Reasons for neonatal mortality are sepsis, immaturity and dysontogenesis. Conclusions have been made for practice in diagnostics and treatment. PMID- 1927107 TI - Receiver operating characteristic curves of fetal, umbilical and uteroplacental blood velocity waveforms as predictors of fetal outcome. AB - The maximum blood flow velocity waveforms (FVW) were recorded by a pulsed Doppler ultrasound from the fetal aorta, umbilical artery and arcuate artery in 142 pregnancies suspected of intrauterine growth retardation (IUGR) according to ultrasound fetometry. The FVW were analysed for pulsatility index (PI) and Blood Flow Class (BFC). The aim of the study was to find the optimal parameter and cut off level for predicting the outcome of pregnancy. Receiver operating characteristic curves were used for the analysis. The umbilical artery PI and BFC shows the strongest relationship to IUGR. The optimal cut-off point was found at 2 SD above the mean PI of the normal population. The aortic PI had a relatively low predictive value for IUGR, but the absence of aortic end-diastolic velocities (BFC 2 and 3) was the best parameter for predicting fetal distress. The arcuate artery PI had low predictive capacity for fetal outcome. The data indicate that the absence of diastolic velocities in the fetal aorta and the umbilical artery PI, with the cut-off level of 2 SD above the mean for the normal population, are the best and comparable blood flow parameters, which can be used for monitoring fetuses suspected of IUGR. PMID- 1927108 TI - [Prenatal diagnosis. Fetal abnormalities in the second half of pregnancy]. PMID- 1927109 TI - [The behavior of serum hCG level in normal and disordered pregnancy--a prognostic factor]. AB - The increase of serum hCG was determined in 305 pregnant women at least twice in the first 10 to 12 weeks of pregnancy. In a large number of cases this was done to rule out a disturbance of pregnancy. The results were evaluated by means of a comparison to the time-dependent changes of the normal range. They were classified in the following manner: 1 = Normally increasing values, 2 = Values lower than normal, but normal increase, 3 = values to low and increasing too slowly, 4 = Serum hCG too low or declining, 5 = initially normal values failing to rise. A type 4 secretion pattern was invariably followed by a demise of pregnancy. In about one half of the cases showing a type 2 pattern, the pregnancy either miscarried or was found to be in an ectopic location. In normal pregnancies, type 2 pattern was found in 29% and type 1 in 71%. A comparison of the results of the first and second hCG determination revealed close agreement in more than 90% of the cases, and in 84% when the comparison was extended to a third sample. PMID- 1927110 TI - [Kolpexin in the conservative treatment of stress incontinence]. AB - A new principle of conservative treatment of stress incontinence is reported combined with our first experiences by using Kolpexin. Clinical and urodynamic results are improved after application of Kolpexin. PMID- 1927111 TI - [An unusual finding in hysterosalpingography]. AB - We report about a case in which inadvertantly as hysterosalpingography was performed in early pregnancy. Radiological findings are described and and the question of risk of radiation is discussed. PMID- 1927112 TI - [Carl Wilhelm Mayer (1795-1868)--founder of the Berlin Society of Obstetrics]. AB - 115 years ago the society of gynaecology and obstetrics in Berlin was found. Already in 1844 the Berlin physician and obstetrician Carl Wilhelm Mayer (1795 1868) has initiated the foundation of a society of obstetrics. This was the first medical-scientific society of the world. We want to demonstrate the biography of C. W. Mayer and also his importance in the creation of a modern medical association. In the second part of present paper, the situation of foundation and the first years of the Berlin society of obstetrics were described. PMID- 1927113 TI - [Management of cervix cancer--yes or no to postoperative radiation treatment after Wertheim operation?]. PMID- 1927114 TI - [Can ulcer treatment with cimetidine and other H2 receptor antagonists induce sexual dysfunctions (impotence) and other endocrine disorders?]. PMID- 1927115 TI - [Psychological preparation for childbirth: what is the value of psychoprophylaxis and the Dick-Read method from today's viewpoint?]. PMID- 1927116 TI - [Considerations on causes of and current therapy variations for tubal pregnancy]. AB - Survey about the newer methods of treatment of tubal pregnancy using methotrexate and prostaglandins. This individualizing therapy has the advantage of avoiding laparotomy. PMID- 1927117 TI - [The treatment of oligozoospermia with tamoxifen does not improve sperm quality]. AB - As contradictory results have been obtained previously concerning the usefulness of tamoxifen in treatment of male infertility, we reevaluated its effects on 29 men presenting with idiopathic oligozoospermia. To determine whether a possible increase in sperm concentration might be correlated with an improvement of sperm quality, the hamster ovum penetration (HOP) test and the hypo-osmotic swelling (HOS) test were including as additional tests of sperm function. Patients were treated with tamoxifen (20mg/day) for 3 months. After already 4 weeks and continuing until the end of the study, tamoxifen had a significant effect (P less than 0.001) on blood levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and estradiol (E2). Prolactin (PRL) concentrations were not altered significantly (P greater than 0.05) after 3 months. There was no significant improvement (P greater than 0.05) of conventional semen parameters (volume, concentration, motility, morphology), and of HOP and HOS test results. Due to this lack of correlation between a rise in hormone levels and improvement of sperm quality, tamoxifen treatment of patients with idiopathic oligozoospermia is of questionable value. PMID- 1927118 TI - [Effect of tamoxifen on parameters of cell-mediated immunity in postmenopausal patients with breast carcinoma]. AB - In 48 postmenopausal breast cancer patients receiving an adjuvant therapy with 30 mg tamoxifen for 22 months on an average the effect of hormonal therapy on different immunologic parameters was examined and compared with an age-matched control group of breast cancer patients without hormonal therapy. Before beginning and after the end of tamoxifen treatment the following examinations were performed: Leucocyte Migrations-Inhibition-Test (LMI-Test) against autologous and homologous tumor and recall antigens, determination of the serum levels of tumor necrosis factor alpha, interleukin 2 and interferon alpha, as well as a determination of lymphocyte subsets (total T-, T-helper-, T-Suppressor- and natural killer cells) in the peripheral blood. Compared to the control group under a tamoxifen therapy the percentage of patients with a migration inhibition in the LMI-test increased, whereas the percentage of patients with an enhancement decreased. There were no changes concerning the LMI-reactivity against recall antigens as well as concerning the serum levels of the different cytokine and the differentiation of T-cell subsets compared to the control group. But we found an increase of natural killer cells. It can be discussed if the clinical effect of a tamoxifen treatment is possibly due to its immunological effect on the nk cell activity. PMID- 1927119 TI - [The effect of adjuvant combined chemo/immunotherapy on immunological parameters and clinical course in patients with breast carcinoma]. AB - In 61 breast cancer patients the effect of an combined adjuvant chemo /immunotherapy with thymopentin (Timunox, Cilag) on different parameters of cell mediated immunity (Leucocyte Migration Inhibition Test, serum level of tumor necrosis factor alpha, IL 2, Interferon alpha and distribution of lymphocyte subsets in the peripheral blood) and the clinical course of disease was evaluated and compared to patients receiving only chemotherapy. In cancer patients additionally treated with thymopentin an increase of the interferon alpha serum level could be observed, whereas the other parameters examined did not change. In the control group the percentage of T helper cells decreased under chemotherapy (p less than 0.05). Due to the short time of observation of 49 months until now no significant changes concerning the disease free interval and the time of survival between both groups could be found. Possibly the additional administration of thymopentin in breast cancer patients at least leads to a reduction of the immunosuppressive side effects of an adjuvant chemotherapy. PMID- 1927120 TI - [Sonographic studies of patients with postmenopausal hemorrhage (endometrium/myometrium index)]. AB - Ultrasonographic examination was performed in 120 patients with post-menopausal bleedings before a diagnostic curettage. In comparison with the final histological diagnoses the sonographic diagnoses were found to be correct in 97 patients (86.2% right-negative; 79.7% right-positive). The proportion of false negative and false-positive results was found to be 12.1% and 16.9% respectively. Specificity and sensitivity values were 83.3% and 87.1%. The endometrium/myometrium-index enabled us to make a good judgment of the endometrium, since it considers both the endometrial and myometrial thicknesses simultaneously. This index was found to be below 0.5 (0.27) in those patients with normal sonographic findings and in patients with pathological sonographic findings it was found to be 1.3. Ultrasound is therefore a non-invasive diagnostic aid for the diagnoses of pathological changes of the endometrium. PMID- 1927121 TI - [Cervical pregnancy--an unusual form of extrauterine pregnancy]. AB - We present a case report about a 27 years old patient with cervical pregnancy. The extrauterine implantation was recognized in the 14th week of gestation. Abdominal hysterectomy was performed because of a life threatening bleeding. PMID- 1927122 TI - [Improvement of the mesh-graft method with use of a fibrin glue. Contribution to the surgical correction of vaginal aplasia]. AB - Congenital absence of the vagina can be corrected by covering the walls of the neo-vagina with skin mesh grafts. We performed this operation in 6 patients, of whom 3 had been operated before without success, and used fibrin sealing for hemostasis and fixation of the grafts. The results were very satisfying. In each case the length of the neo-vagina has completely been maintained until now, without any shrinking or shortening. PMID- 1927123 TI - [Cardiotocography practice. CTG Practice 20]. PMID- 1927124 TI - [What is the significance if post-sterilization syndrome following tubal electrocoagulation?]. PMID- 1927125 TI - [Neonatal screening--a brief review]. PMID- 1927126 TI - [Inflammatory diseases of the breast]. PMID- 1927127 TI - [Immunofluorescence detection in Chlamydia trachomatis in cervical smears using monoclonal antibodies]. AB - The early detection of chlamydial infections is very important because they may cause cervicitis, endometritis and salpingitis and because of that reason for sterility in women. In routine cervical smears the morphologic picture is aspecific. One of the most specific methods for identification of Chlamydia trachomatis is the direct immunofluorescence with monoclonal antibodies (DIF). 100 women of age 18 - 45 years are examined with DIF test produced by Orion Diagnostica. In the cytological smears of 15 women morphological signs, inclusion and vacuolization, suspicious of Chlamydia trachomatis infection were seen. Using DIF, positive reactions have been found in 17 women. A conclusion for the high specificity of DIF with monoclonal antibodies is made. PMID- 1927128 TI - [Manual palpation of the uterine scar following vaginal delivery in previous cesarean section--is it really necessary?]. AB - 85 vaginal deliveries following a previous cesarean section were registered during a period of 10 years. After 43 deliveries a palpation of the uterine scar had been carried out. In 42 cases the observation of clinical progress and of the laboratory parameters was preferred. An uterine rupture did not occur. This appears to justify the more expectant attitude in controlling the uterine status after vaginal deliveries following a previous cesarean section. PMID- 1927129 TI - [Efficacy of adjuvant chemotherapy in metastasizing cervix carcinoma. A pilot study]. AB - There are reported preliminary results of a pilot-study in the postoperative adjuvant treatment of cervical carcinoma with involvement of the iliac lymph nodes. It was done a prospective randomized study. There were 3 groups of treatment: adjuvant chemotherapy with a combination of Cisplatin and 5 Fluorouracil over 6 cycles; adjuvant chemotherapy like in the first group over 3 cycles plus Telecobalt-irradiation till the doses of 50 Gy in the small pelvis; and postoperative irradiation with Telecobalt till the doses of 50 Gy in the small pelvis. The fate of 41 patients could be evaluated. There were no statistical differences between the 3 groups in age, histology, staging and follow-up. Also the survival rate and the rate of the disease-free time didn't show a significant difference, but it seems, that the chemotherapy with Cisplatin and 5-Fluorouracil could be able to improve the poor prognosis of the cervical carcinoma with metastases. PMID- 1927130 TI - [Inter- and intra-individual variability of pharmacokinetic parameters for contraceptive steroids]. AB - Serum levels of ethinylestradiol (E2) and levonorgestrel (LNG) have been determined in 10 volunteers of similar age after administration of 1 tablet of the oral contraceptives Gravistat and Ediwal, respectively, each containing 0.05 mg E2 and 0.125 mg LNG, using a cross over design. The studies were carried out at intervals of 4 weeks, within the follicular phase of the menstrual cycle and under standardized conditions. Wide variations were observed between the women in the calculated pharmacokinetic parameters, while there was a relatively close correspondence between the intra-individually obtained values, except for one case. PMID- 1927131 TI - [Computerized tomography of a vesico-vaginal fistula caused by a foreign body]. PMID- 1927132 TI - [Hystero-contrast-sonography--a new alternative for the monitoring of fallopian tube patency?]. PMID- 1927133 TI - [Risk assessment in twin pregnancy]. AB - 248 twin pregnancies had been examined retrospectively between 1980 and 1988. Each case of twin pregnancy was confronted with a singleton pregnancy of similar age and parity as matched-pair. Aim of the study was to examine the course of delivery as well as fetal outcome. Main reasons of prematurity have been preterm uterine contractions and rupture of fetal membranes. Rates of cesarean sections had been 41.2 per cent in twin pregnancy and 18.8 per cent in singleton ones. Apgar score had been better in singletons. Ph of umbilical artery had similar values in singleton pregnancy and first twin, but lower values in the second twin. Also nowadays twin pregnancy is a risk pregnancy with a 2.3 fold higher perinatal mortality compared with singleton pregnancy in our matched-pair-group. PMID- 1927134 TI - [Detection of calcitonin and parathyroid hormone in the human placenta]. AB - Detection of calcitonin and parathyroid hormone in the human placenta at term. In this investigation we proved immunoreactive calcitonin and immunoreactive parathyroid hormone in the maternal side of the human placenta. We used the immunocytochemical staining technique (Peroxidase-Antiperoxidase-method) by Sternberger where different antibodies react. We could see calcitonin and parathyroid hormone mainly in the decidual cells as well as in the cytotrophoblastic cells of the maternal part of the placenta. PMID- 1927135 TI - [The effect of pregnancy and parity on the venous system of the leg]. AB - Pregnancy is a risk factor for development of varicosis. The reason remains unclear. Because of the secondary diseases like thrombosis, pulmonary embolism and chronic cardial and respiratory diseases treatment of risk factors is important. Therefore we examined 54 patients with sonography and venous occlusion plethysmography before and immediately after delivery. Some of the patients could be reexamined one month and one year following delivery. All veins had a significant exaggerated distensibility post partum. Other functional parameters were not changed. In another study 50 primiparae and 50 multiparae before and after childbirth and 100 women between age 40 and 50 had been examined with light reflection rheography. Pregnancy per se had a negative influence on venous function. Phlebological status had to be included into prenatal care. PMID- 1927136 TI - [HELPP syndrome as a threatening postpartum complication]. AB - A fulminant course of HELLP-Syndrome appears without important premonitory manifestations (prodrome) many hours postpartum with an eclamptic attack. The initial available diagnostic problems and the essential therapy have been exposed. The important point of the treatment is the blood exchange (fresh blood) combined with haemodialysis. By that the life of the puerperal woman is not in danger. PMID- 1927137 TI - [Which methods belong in the diagnostic work-up of fluor genitalis today?]. PMID- 1927139 TI - [Postoperative evisceration]. AB - From 1930 to 1989 postoperative rupture of abdominal wound occurred in 0.42 per cent (n = 82) in the Department of Obstetrics and Gynaecology of the University of Rostock. 60 per cent of the patients were younger than 50 years. Patients of reduced general condition and anaemia were predisposed to this complication. We observed postoperative alterations of the respiratory tract in 13 per cent and alterations of the gastro-intestinal tract in 20 per cent which lead to increased intra-abdominal pressure. We observed postoperative wound rupture only in 8 cases after Pfannenstiel's incision, but all other times after median section, predominantly during the 7th and 12th postoperative day. All patients were treated by secondary suture, immediately. 8 patients came to death, three of them had no direct link to wound rupture. For prophylaxis the use of non-absorbable suture material, safety sutures, intraoperative blood and protein substitution and prevention of affections of the respiratory system and gastrointestinal tract are recommended. PMID- 1927138 TI - [Endothelial cell damage in pre-eclampsia]. AB - It was the aim of this paper to report on new estimations from the literature suggesting that vessel endothelial cell injury may be a very pathologic process in preeclamptic women. These reports relate to structural vessel endothelial cell damages in and outside of the placenta bed and in other body sides. Furthermore there are indirect estimations that indicate elevated plasma fibronectin concentration before preeclamptic symptoms becomes apparent, the activation of the coagulation cascade by damaged endothelium, the known reduced prostacyclin synthesis, an increased mitogenic activity and the occurrence of anti-endothelial cell antibodies in preeclamptic women, an increased number of circulating desquamated vessel endothelial cells in peripheral blood in patients with preeclampsia and an increased cytotoxic activity of preeclamptic serum against umbilical vein endothelial cells. These findings will be discussed. PMID- 1927140 TI - [Sexual development: development of secondary sex characteristics--Tanner stages 25 years later]. AB - In a longitudinal study the british pediatrician J.M. Tanner evaluated the development of breasts (thelarche), of pubic hairs (pubarche) and age of menarche. In Hungary we did a similar evaluation in 680 girls in the years 1980 to 1986. Comparing these data in a cross-sectional study with similar data from Munster we named the results central-european study. The results are similar the Tanner ones exceptionally the duration of breast development, which was shorter than in the hitherto published longitudinal studies. Mean age of menarche in our study was 12.5 years compared with 13.5 years in the former ones. This is not a confirmation to acceleration of puberty, because in other countries age of menarche was stabile. Additionally, to thelarche, pubarche and menarche we collected data about axillarche. PMID- 1927142 TI - [Prenatal diagnosis and postpartal therapy of a rare sequela of gastroschisis: short bowel syndrome]. AB - Report about a rare complication of gastroschisis by early volvalus. Following this occasionally the prenatal diagnosis there was a very ultrasonogram of a mostly solid tumour before the abdominal wall. The postpartal operative therapy with resection and later doubling according to Bianchi B described. PMID- 1927141 TI - [Pregnancy termination in the 2d and 3d trimester with prostaglandins depending on the cervix status]. AB - Termination of pregnancy was performed in a standardized, on the cervical state depending manner in 48 patients with abortion between the 16th and 27th week of gestation and in 20 women with intrauterine fetal death (IUFD) between the 28th and 41st week of gestation. At a Bishop-Score (B.S.) less than 7 cervical ripening was induced by intracervical application of 0.1 mg sulprostone gel. In patients with a very unripe cervix (B.S. less than or equal to 3) local applications of prostaglandin gel were repeated at 6 hours intervals until a B.S. greater than or equal to 5 had been achieved. For induction of labour 0.5 mg sulproston was injected intramuscularly after at least one sulproston gel application in a range between B.S. greater than or equal to 5 to 7. At a B.S. 7 intravenous infusion of oxytocin was administered, if necessary, for augmentation of labour. Most of the patients received epidural anaesthesia before induction of labour. The time interval between the beginning of the procedure and expulsion of the fetus ranged from 6.5 to 49.5 hours (mean = 26.3 h) in the abortion group and from 2.0 to 46.0 hours (mean = 20.0 h) in the IUFD group. The median interval between induction of labour and abortion/delivery was 4.3 hours (range: 0.5 27.0), and 5.5 hours (range: 0.7-9.3 h) respectively. No surgical interventions were necessary in any of the patients, and no cervical lesions occurred. Undesired systemic side effects to prostaglandins were observed in only 4 out of the 68 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927143 TI - [Spring meeting of the Society of Gynecology and Obstetrics of the Leipzig and Chemnitz districts 4. 5. 1990 in Chemnitz]. PMID- 1927144 TI - [Can sodium fluoride still be administered today in the treatment of osteoporosis?]. PMID- 1927145 TI - [What is meant by the 2-pool model of gonadotropin secretion in the female?]. PMID- 1927146 TI - Detection of porcine MHC class II antigens in different immunoassays. AB - A monoclonal antibody (Mab), Mab 4-24-11, to human class II major histocompatibility antigens has been tested in commonly used immunoassays for detection of porcine class II major histocompatibility antigens (SLA-D). In a radioimmunoprecipitation assay, Mab 4-24-11 reacted with proteins from mitogen stimulated porcine mononuclear cells (MNC). The molecular weights of the precipitated proteins were approximately 34 and 28 Kd. In indirect immunofluorescence, approximately 25% of porcine MNC in suspension reacted with Mab 4-24-11. This percentage diminished to 14% when Ig bearing MNC were removed, while it increased to 36% when adherent MNC were enriched. Thus, it was concluded that Mab 4-24-11 cross-reacts with SLA-D. In a immunohistochemical study, Mab 4 24-11 reacted with cells in acetone fixed cryostat sections from the gastric mucosa and endometrium. These properties of Mab 4-24-11 make it useful as a tool for further studies on the porcine immune system. PMID- 1927147 TI - [The biology of Dipylidium caninum. Part 2]. AB - From 198 cats and 182 dogs in Austria 9,134 fleas were collected. Ctenocephalides felis is the main flea of our cats (98.5%) and dogs (77.5%). Demonstration of cysticercoids of Dipylidium caninum through bleaching of fleas failed. Dissection of fleas gave, however, positive results. Each 44th flea from cats and 61st flea from dogs harbours cysticercoids. Infection intensity rates were 2.3% for C. felis (cats), 1.2% for C. felis (dogs), and 3.1% for C. canis (dogs). Male fleas are more extensively, but less intensively infected than female fleas. Cysticercoids form fleas of feline origin are more infective to cats than those from fleas found on dogs. The longest patency in cats lasted 3 years. PMID- 1927148 TI - Experimental examinations concerning the problem of deformed emerging bees after infestation with Varroa jacobsoni. AB - The deformations of bees occurring in connection with varroatosis was examined both in case of natural and artificial infestation. Under both conditions, the number of bees showing wing deformations increased with the degree of mite infestation. Shortened abdomina, however, only appeared in the case of natural infestation. Inadequate brood care in colonies severely infested by Varroa mites is supposed to be responsible. Wing deformations could be produced by experimental haemolymph extraction. PMID- 1927149 TI - Characterization of toxin from different strains of Pasteurella multocida serotype A and D. AB - Chromosomal DNA from 13 different selected Pasteurella multocida spp. multocida strains of serotypes A and D were isolated and compared. All 10 toxigenic strains were recognized by a DNA probe which included the toxA gene coding for the Pasteurella multocida toxin (PMT). None of the three nontoxigenic strains reacted with the DNA probe. Toxin from the 10 toxigenic strains were isolated and compared. All were found to possess the biological characteristics previously described for the PMT isolated from P. multocida ssp. multocida NCTC 12178, including molecular mass of approx. 143 kDa and reactivity with a series of monoclonal antibodies. Toxin prepared from different toxigenic strains could not be differentiated immunologically by tandem crossed immunoelectrophoresis, Toxin, which was affinity purified from four of the strains and subsequently inactivated by formaldehyde, was cross-protective when used for vaccination of mice before challenge with PMT. It is concluded that the toxin from toxigenic strains of P. multocida ssp. multocida must be very similar, if not identical. PMID- 1927150 TI - Automation of the resazurin reduction test using fluorometry of microtitration trays. AB - Microtitration plate technique and -fluorometry was applied to automate the resazurin reduction test for monitoring bacterial numbers in broth cultures and milk. The effect of resazurin and resorufin concentration, bacterial species, growth medium, pH, and redox potential on the fluorescence response was studied. The timing of the appearance of maximum fluorescence was directly related to the logarithm of the number of colony-forming units (log CFU). Fresh milk and heat treated milk contain interfering redox systems. The technique based on microtitration plate fluorometry, when fully automated, seems to provide a high capacity system for analyzing bacterial numbers in foodstuffs and other media. PMID- 1927151 TI - Experimental infection of the udder of ewes due to Mycoplasma bovis. AB - Twelve freshly lactating ewes were experimentally infected with 2 Mycoplasma (M.) bovis strains via the teat canal in the left udder. The M. bovis infection produced a febrile clinical mastitis in all infected animals. M. bovis could be re-isolated regularly from the experimentally infected udder halves and the infection spread to the other halves. Some contact animals and 4 suckling lambs became naturally infected. Antibody titres were detected by means of the indirect hemagglutination test in blood sera 2 to 3 weeks post infectionem. The pathological lesions were similar to those of the M. bovis mastitis of cows. By the end of the trial the ewes had recovered from the clinical mastitis. PMID- 1927152 TI - [Carbohydrate and lipid metabolism in swine skeletal muscle in the pre- and neonatal periods]. AB - Studies have been made on the activity of hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malate dehydrogenase and isocitrate dehydrogenase, as well as on the intensity of in vitro oxidation of [U-14C]-glucose and [U-14C]-palmitate (together with in vivo lipid synthesis from these compounds) in porcine skeletal muscles during pre- and postnatal periods of life. It was shown that active utilization of glucose in oxidative metabolism and lipid synthesis is possible during the transition from prenatal to neonatal period. The increase in the rate of oxidation of fatty acids in skeletal muscles of piglets, in contrast to other animals, does not inhibit carbohydrate utilization. PMID- 1927153 TI - [The effect of serotonin on the heart contraction frequency in the suslik Citellus undulatus depends on the environmental temperature]. AB - In experiments on active ground squirrels, it has been shown that the effect of intraperitoneal injection of serotonin on the heart rate depends on the dose and the environmental temperature. At relatively low doses and high environmental temperature, serotonin increases the heart rate and body temperature; on the contrary, with the increase in the dosage and the decrease in the environmental temperature the heart rate and body temperature of animals decrease. It is suggested that this relationship serves as one of the factors which enhance the transition of animals from one level of activity to another during the beginning and the end of hibernation. PMID- 1927155 TI - [The dynamics of the index of stress in ontogeny]. AB - Mathematical analysis of the heart rate in foetuses reveals the progressive development of regulatory mechanisms which account for fetal maturity. The decrease in sympathetic tonic mechanisms, the onset and development of normo- and vagotonic mechanisms of regulation of chronotropic function of the heart were revealed in postnatal ontogenesis. Phasic structure of regulatory processes during the increase in loading was observed in the organism of children, infants and young subjects. PMID- 1927154 TI - [Changes in thermoregulation, sleep and the thyroid hormone concentration of the blood in the "critical" period of the entry into hibernation of the suslik Citellus parryi]. AB - During the first entering into hibernation in the ground squirrels there are periodic cessations of the process, especially during the transition to moderate and deep torpidity ("critical" periods) which significantly increase energy expenditure in animals during the phase of entering. During this period, high amplitude near-the-hour fluctuations are observed in total duration of wakefulness and sleep, contractile muscle activity, oxygen consumption, heart rate, brain temperature, and thyroid hormone concentration in the blood; at the end of this period, as well as during the exiting from it the duration of deep slow wave sleep significantly increases, paradoxical sleep is not identified. The data obtained confirm a hypothesis of "kindling" homeostasis as neuro-hormonal mechanism of the increase in thermal range of the activity of functional systems of the organism during the entering into torpidity in homoiothermic animals. PMID- 1927156 TI - [The effect of long-term hyperbarism on pregnant guinea pigs and their progeny]. AB - The effect of hyperbarism has been investigated on 1-3-, 4-5- and 8-10-week pregnant rats and their offsprings. It was found that the mortality rate of pregnant rats is two times higher after hyperbaric exposures than in control animals. The animals exhibit the highest sensitivity at a stage of 8-10 weeks. Hyperbaric conditions significantly affect offsprings. Only 53% of newborn puppies were found to be normal, whereas 35% were born dead and 12% revealed various abnormalities. The highest sensitivity was observed during organogenesis (4-5 weeks), the mortality rate during this period reached 70%. The body mass in newborn puppies was significantly lower than in control animals. The most significant retardation in the development was observed in animals which were subjected to the effect of hyperbarism at the 4-5-th week of intrauterine life. PMID- 1927157 TI - [The effect of light stimulation in the pre- and postnatal periods on the synaptic ultrastructure in the chick hyperstriatum]. AB - Morphometric analysis of synapses in the medial parts of the ventral and accessorium hyperstriatum in the right and left hemispheres in chicks has been performed after rhythmic optic stimulation from the 18th day of incubation, flickering stimulation at the 11-12th hour after hatching, as well as in chicks reared under normal illumination and those kept in darkness within the first two days after hatching. Numeric density of synapses, mean dimensions of postsynaptic thickenings, the number of synaptic vesicles per active zone in presynapses and mean length of the whole axodendritic contact were determined in ultrathin sections. The data obtained indicate that early visual experience significantly affects the synaptic structures in both parts of the brain. A discussion is made of the plasticity of synapses during stimulation, morphological and functional relationships between hyperstriatal areas in relation to different aspects of processing and storage of visual information. PMID- 1927158 TI - [The reaction of the thyroid in the frog Rana temporaria to arginine-vasotocin administration]. AB - Using morphometric technique, it has been shown that single and especially three successive injections of a hypothalamic nonapeptide neurohormone, arginin vasotocin (5.10(-9) M/kg of body weight) affect functional activity of the thyroid gland in sexually mature male frogs which had been subjected to hypophysectomy 10 or 60 days before neurohormonal treatment. These data presumably confirm a hypothesis about the direct para-adenohypophysial influence of the hypothalamic nonapeptide neurohormone on the peripheral endocrine glands, particularly, the thyroid one. PMID- 1927159 TI - [The rate of the evolution of mitochondrial DNA in salmonid fishes]. PMID- 1927160 TI - [The possible mechanism of the transmission of stress effects from mother to progeny in mammals via the placenta and the milk (the stressin hypothesis)]. PMID- 1927161 TI - Integration of pecking, filter feeding and drinking mechanisms in waterfowl. AB - This paper is one of several contributions in a series, illustrating the application of a specific deductive methodology to explain diversity of form. The methodology facilitates the explanation of feeding morphologies in various ducks as a transformation of the mallard's feeding design maximized for specific proportions of performance that are contributed by pecking and filter feeding mechanisms. The earlier described anatomy and formal analyses of the three mechanisms in the mallard served as the initial conditions used in simulation models. Four elements of the feeding system were chosen that play a major role in all three mechanisms. For each element, the main parameter was selected: storage capacity of the rostral mouth cavity, transport capacity of the rostral mouth tube, storage capacity of the caudal mouth cavity and transport capacity of the caudal mouth tube. The boundary conditions for the simulation were determined from internal organismic constraints. The total food uptake of the mallard was regarded as the function to be maximized. This 'object' function is the summation of the food uptake by one second of pecking and one second of filter feeding. The drinking mechanism was shown not to interfere, since that mechanism operates sufficiently whenever the pumping mechanism works properly. The 'object' function, made up by the pecking and filter feeding performances was graphed. From these graphs a morphospace was developed: the region within which modifications of the mouth design are feasible. This procedure allowed examination of the general hypothesis that different modifications of one design for a complex multi-role system are explainable from differences in proportions of the functional performance contributed by each of the roles. Two predictions were evaluated more specifically: 1) If filter feeding performance must increase for a specific change in total food uptake, the volume of the rostral mouth cavity must increase; this requires widening and lengthening of the rostral maxillar portion and also a phase shift in jaw and lingual motion patterns, increasing the stroke volume. 2) If pecking performance must increase, the transport capacity of the rostral mouth tube must increase; this requires shortening of the maxillar mid portion. These two predictions regarding change in mouth morphology were borne out by shovelers and tufted ducks, respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1927162 TI - The Donne axiom: no human brain is an island. An unused way to look at the brain and to couple it to mind. AB - In the case of human brains significant functional connections and exchange of information exist not only within brains, but also between them (given language). Connected human brains constitute a physiological entity, which should be taken into account when modeling human brain functions. PMID- 1927163 TI - The diabetic heart: clinical, experimental and pathological features. AB - Patients with diabetes mellitus are particularly vulnerable to cardiovascular disease. Although both the macrovascular and microvascular complications are present in patients with diabetes alone, they are particularly severe in patients with both diabetes and hypertension. While there is no doubt that a primary diabetic cardiomyopathy occurs with functional consequences, considerable evidence--both in humans and in experimental animal models--points to hypertension as of critical importance in the pathogenesis of severe pathological and symptomatic diabetic heart disease. In hypertensive-diabetic cardiomyopathy, the histopathologic myocardial damage has been attributed to hypertension, while the myocellular dysfunction has been attributed to diabetes. Together, the consequences to the myocardium are devastating. Strict control of the hypertension and diabetes mellitus, along with prevention of the microvascular consequences of both conditions, may have an ameliorative effect on the subsequent development of diabetic heart disease. PMID- 1927164 TI - Sex hormones and cardiovascular risk. PMID- 1927165 TI - The cardiac renin-angiotensin system: a synopsis of current experimental and clinical data. AB - Local tissue-resident renin-angiotensin systems are increasingly being recognized as important neurohumoral mediators which may act in concert with, but also independently of the circulating system. Here we review the evidence supporting the existence, functional integration, and physiopathological role of a cardiac renin-angiotensin system which has recently been defined. The elements of the catalytic cascade of the system, renin, angiotensinogen, and angiotensin converting enzyme have all been demonstrated in cardiac tissues, both on the protein-level and with regard to local expression of the respective genes. Modulation of gene expression in response to various perturbations has been demonstrated, and may occur independently of the plasma or other tissue renin angiotensin systems. In isolated hearts, generation of the biologically active peptides, angiotensin I and II, has been documented, establishing the capability of this system to act as an independently regulated, functionally integrated catalytic pathway for the production of angiotensin II. Through specific receptors, present in the heart as in other tissues, angiotensin mediates profound effects on cardiomyocyte function and, as we are beginning to learn, on structure and growth. Furthermore, indirect evidence based on specific, beneficial effects of angiotensin converting enzyme inhibiting drugs which are distinct from those of other vasodilators, points to the potential role which this local system may play for physiological function of the heart as well as in a number of pathological derangements of the cardiovascular system. PMID- 1927166 TI - Role of the endothelium in the regulation of coronary artery tone. PMID- 1927167 TI - Endothelium-mediated control of coronary circulation. PMID- 1927168 TI - Regulation of human cardiac myosin heavy chain gene expression by thyroid hormone in cultured fetal rat heart cells. PMID- 1927169 TI - Bronchial granular-cell tumor. Report of a case with preoperative cytologic diagnosis on bronchial brushings and immunohistochemical studies. AB - A 42-year-old man presented with a polypoid endobronchial mass of the right apical segmental bronchus. Bronchial brushing smears contained clusters of cells exhibiting abundant diffusely granular cytoplasm with indistinct borders. A cytologic diagnosis of granular-cell tumor was rendered. Histologic examination of the upper right lobectomy specimen provided confirmation. Immunohistochemically, the granular cells strongly reacted with the S-100 protein antibody. This case demonstrates that the cytologic diagnosis of bronchial granular-cell tumor is possible if this lesion is considered in the differential diagnosis of lung tumors. PMID- 1927170 TI - Cytology of bronchial benign granular-cell tumor. AB - The cytologic features of a case with multiple bronchial benign granular-cell tumors are reported and compared with those of previously reported cases. Characteristic tumor cells were found in the bronchoscopic brushing smears and in cell block sections (but not smears) prepared from the washing fluid. These findings were confirmed by the bronchial biopsy and histologic study of the resected tumors. A cytologic diagnosis of bronchial granular-cell tumor should not be difficult because the cytologic appearance of the tumor cells is characteristic; however, the possibility of a concomitant tumor, such as adenocarcinoma or small-cell carcinoma, should be considered and excluded. PMID- 1927171 TI - Conventional respiratory cytology versus fine needle aspiration cytology in the diagnosis of lung cancer. AB - The results of 184 fine needle aspiration (FNA) cytologic examinations were compared with the findings of "conventional" respiratory cytology (on sputums, bronchial brushings and bronchial washings) and histology (on biopsy and autopsy samples) and with the medical records. Positive cytologic results were obtained in 6 (10%) of 60 sputums, 17 (21%) of 80 brushings, 16 (19%) of 84 washings and 82 (44%) of 184 aspirates. These positive results were confirmed by biopsy for 6 of 6 sputums, 16 of 17 brushings and 15 of 16 washings. Among the 82 patients with a positive FNA cytology, malignancy was confirmed by lung biopsy in 39 and by autopsy in 2; the cytologic diagnosis was supported by clinical and radiographic findings in all but 1 of the remaining 41 patients. Using transbronchial lung biopsy, autopsy and medical records as final standards, the positive predictive values were 100% for sputum, 94.1% for brushings, 93.0% for washings and 98.6% for FNA samples. The high positive predictive values of FNA and the other cytologic procedures indicate that these diagnostic modalities provide simple, rapid and reliable methods for the diagnosis of lung cancer. PMID- 1927172 TI - Presentation of Sporothrix schenkii in pulmonary cytology specimens. AB - Macrophages containing small ovoid intracytoplasmic yeast cells, surrounded by a slight "halo," were observed in Papanicolaou-stained smears of sputum submitted for cytologic examination from two patients with culture-confirmed pulmonary sporotrichosis. The cytologic findings are presented and discussed in relation to other pulmonary fungal infections and the appropriate stains to be used for their cytologic detection. The clinical symptoms of pulmonary sporotrichosis are nonspecific and may mimic those of tuberculosis or other diseases; the causative organism, Sporothrix schenkii, may remain undetected by routine microbiologic procedures unless there is cause to suspect the diagnosis. Sporotrichosis should be considered in the differential diagnosis when small ovoid intracellular yeast cells (2 microns to 4 microns in length) with an apparent "halo" are observed within macrophages in pulmonary cytology specimens; the recognition of these findings may aid in the diagnosis of this relatively rare disease. PMID- 1927173 TI - Fine needle aspiration cytology, immunocytochemistry and electron microscopy of fibromatosis of the breast. Report of two cases. AB - Two cases of primary fibromatosis of the breast are described. The lesions were suspected to be carcinomas both clinically and mammographically. Fine needle aspiration (FNA) yielded bland-appearing isolated spindle cells associated with small groups of benign ductal cells and lymphocytes. Immunoperoxidase staining performed on the original FNA smears showed positivity for vimentin and muscle specific actin only in the spindle cells and for cytokeratin only in the epithelial cells. Electron microscopy study of one case demonstrated the ultrastructural characteristics of well-differentiated fibroblasts and myofibroblasts. PMID- 1927174 TI - Fine needle aspiration cytology, immunocytochemistry and electron microscopy in a rare case of carcinoma of the breast with malignant epithelial giant cells. AB - The cytohistologic findings in a fine needle aspirate from a case of the rare breast carcinoma with bizarre tumor giant cells are described, along with the results of immunocytochemical and ultrastructural studies. The observations in this case suggest that the bizarre malignant giant cells in this type of breast cancer are of an epithelial origin, rather than a histiocytic-stromal origin. The other conditions that may yield giant cells in needle aspirates of breast masses are briefly discussed. PMID- 1927175 TI - Thyromegaly secondary to simultaneous papillary carcinoma and histiocytosis X. Report of a case and review of the literature. AB - The cytologic and histologic findings are reported in a case of papillary carcinoma arising within a thyroid gland pathologically enlarged by histiocytosis X. Fine needle aspiration (FNA) biopsies of a thyroid nodule in a patient with longstanding histiocytosis X produced a scanty amount of colloid, a moderately dense mixed inflammatory infiltrate and numerous small papillary fragments lined by cuboidal-to-columnar cells. Both the inflammatory cells and the epithelial cells showed nuclear grooves; the two populations of neoplastic cells were distinguished, and the correct diagnosis of the nodule was made, by recognizing the greater amount of granular cytoplasm of the mononucleated Langerhans' cells. The rare involve-of the thyroid by histiocytosis X is reviewed; this case, which appears to be the first reported instance of the co-occurrence of histiocytosis X and papillary carcinoma of the thyroid, indicates that patients with histiocytosis X should be observed for the development of thyroid carcinoma and that FNA biopsy can make the distinction between the two conditions. PMID- 1927176 TI - Necrosis in thyroid nodules after fine needle aspiration biopsy. Report of two cases. AB - Two cases of infarction of thyroid neoplasms following fine needle aspiration (FNA) biopsy are reported. Histologic study of a 2.5 x 2.5 cm nodule excised 18 days after FNA had diagnosed a Hurthle-cell neoplasm showed mainly necrotic debris and granulation tissue. While FNA made the diagnosis of a papillary carcinoma in the second case, which had had an FNA biopsy of the same nodule six years earlier, most of the nodule was fibrotic and necrotic. These two cases demonstrate the potential problems in such cases: (1) post-FNA infarction may obscure the nature of a cytologically diagnosed neoplasm, making histologic confirmation difficult, and (2) FNA of an infarcted nodule may have difficulties in obtaining diagnostic material, potentially resulting in a false-negative diagnosis. Review of the literature on thyroid infarction shows it to be a rare event, with most reported cases occurring after FNA biopsy of a neoplasm. The finding of necrosis and fibrosis in an aspirate or surgical specimen should thus suggest the presence of a neoplasm. PMID- 1927177 TI - Invasive cervical thymoma masquerading as a solitary thyroid nodule. Report of a case studied by fine needle aspiration. AB - A 49-year-old woman underwent fine needle aspiration (FNA) biopsy of a presumed thyroid nodule. The initial cytopathologic interpretation suggested a chronic lymphocytic thyroiditis or a malignant lymphoma. The examination of frozen sections during surgery also suggested the presence of a lymphoma. However, histopathologic examination of permanent sections showed the lesion to be an invasive ectopic lymphocyte-predominant thymoma adjacent to the thyroid. Immunoperoxidase staining of FNA cell block sections and permanent sections showed positivity for keratin, proving the epithelial nature of the elongated and spindle-shaped tumor cells. This case high-lights the need to be aware of unusual lesions that may occur in the area of the thyroid; recognizing the potential diversity of "thyroid" masses that ultimately prove to be of nonthyroid origin should aid in making the correct cytologic differential diagnosis and interpretation of FNA samples obtained from such masses. PMID- 1927178 TI - Fine needle aspiration biopsy in the diagnosis of thyroid nodules. AB - The fine needle aspiration (FNA) biopsies performed on thyroid nodules at Turku University Central Hospital from 1983 to 1988 were reviewed. Of the 1,054 total aspirated nodules, 194 were investigated histologically after thyroid surgery (191 cases) or at autopsy (3 cases). Two cases with an insufficient FNA sample, 4 with an incidental occult papillary carcinoma and 2 cases with carcinoma outside the nodule investigated by FNA biopsy were excluded from the series, leaving 186 histologically confirmed nodules in the final analysis. Three (3%) of the 107 cases with an FNA biopsy diagnosis of benign, 4 (8%) of the 52 with an FNA diagnosis of equivocal, 3 (20%) of the 15 with an FNA diagnosis of suspicious and all 12 (100%) with an FNA diagnosis of malignant were histologically malignant. If only an unequivocally malignant cytologic finding is considered positive, FNA biopsy had a diagnostic specificity of 100%, a sensitivity of 55% and an accuracy of 95% among the histologically confirmed cases. Follow-up revealed no cases of cancer among the 863 thyroids that were not explored surgically. It is concluded that FNA biopsy is a practical method with considerable diagnostic value in the evaluation of thyroid nodules. PMID- 1927179 TI - Hodgkin's disease presenting as an enlarged thyroid gland. Report of a case diagnosed by fine needle aspiration. AB - An unusual case of Hodgkin's disease (HD) in a 36-year-old woman that was diagnosed by fine needle aspiration (FNA) biopsy of a neck mass believed clinically to be diffuse goiter is reported. The aspirate was composed mainly of dispersed lymphocytes; admixed with these were occasional large mononuclear cells with round-to-oval nuclei and prominent nucleoli. Binucleated variants of the large cells were interpreted as Reed-Sternberg cells, suggesting the diagnosis of HD. Subsequent to the FNA biopsy, radiologic examinations demonstrated an enlarged mediastinum, and incisional biopsy of the neck mass confirmed the diagnosis of HD. This case emphasizes the value of FNA biopsy as a rapid and reliable procedure, even in the unusual but established clinical presentation of HD as a diffuse neck mass. PMID- 1927180 TI - Aspiration cytology of renal-cell carcinoma metastatic to the thyroid. AB - Fine needle aspiration (FNA) of a thyroid mass clinically suspected of being acute thyroiditis led to a cytologic diagnosis of hypernephroma metastatic to the thyroid and to the subsequent detection of the occult primary tumor. The FNA cytomorphologic findings were substantiated by cytochemical staining of FNA samples and confirmed by subsequent histopathologic examination of the resected thyroid. Postoperative studies revealed an expansive growth in the left kidney; analysis of the nephrectomy specimen showed an invasive renal-cell carcinoma. This case emphasizes the considerable value of FNA biopsy in making the frequently difficult preoperative differential diagnosis of primary and metastatic thyroid tumor and the importance of cytochemical analyses in making that distinction and in suggesting the site of the primary tumor. PMID- 1927181 TI - Fine needle aspiration cytology of cystic parathyroid lesions. A cytomorphologic overlap with cystic lesions of the thyroid. AB - Three cases of palpable cystic parathyroid nodules examined by fine needle aspiration (FNA) cytology are reported. Two of the three aspirates were incorrectly identified as thyroid neoplasms due to the presence of papillary clusters or microfollicles and grossly golden-brown cyst fluid. Histologic examination of these two nodules revealed partially cystic parathyroid adenomas. Aspirated material from the third patient yielded clear watery fluid, which was correctly identified as consistent with a parathyroid cyst. The diagnostic difficulties in the differentiation of parathyroid adenoma from thyroid carcinoma or adenoma are discussed, as is the utilization of assays for parathyroid hormone in making the FNA diagnosis of parathyroid lesions. PMID- 1927182 TI - Cytodiagnosis of gastric ulcer penetration of the liver by examination of endoscopic brushings. AB - The penetration of a gastric peptic ulcer into the liver was initially diagnosed by the cytologic examination of endoscopic brushings and later confirmed by an endoscopic biopsy of the stomach. One of the smears of the gastric brushing contained sparse groups of liver cells with mild atypia. The endoscopic biopsy specimen included liver parenchyma with signs of peptic hepatitis. The differential diagnostic considerations for a gastric brushing containing hepatoid cells are discussed. PMID- 1927183 TI - Pleomorphic ("dedifferentiated") chondrosarcoma. Report of a case initially examined by fine needle aspiration biopsy. AB - Fine needle aspiration (FNA) biopsy of a predominantly radiolucent, destructive lesion of the right distal femoral metaphysis of a 69-year-old man produced smears containing spindle-shaped cells with cytologic features consistent with a malignant fibrous histiocytoma. This initial diagnosis was supported by immunoperoxidase staining, which was strongly positive for vimentin and alpha-1 antichymotrypsin, focally positive for S-100 protein and negative for desmin, muscle-specific actin, keratin, carcinoembryonic antigen and epithelial membrane antigen. Subsequent surgical resection revealed a lesion with a predominance of malignant fibrous histiocytoma-type regions; however, focal microscopic areas contained a low-to-medium-grade cartilaginous component. The final diagnosis rendered was thus pleomorphic or so-called "dedifferentiated" chondrosarcoma. This rare lesion should be included in the differential diagnosis of malignant spindle-cell lesions of bone assessed by FNA biopsy. PMID- 1927184 TI - Infarction of a papillary thyroid carcinoma after fine needle aspiration. PMID- 1927185 TI - Evaluation of erythropoiesis by new methylene blue staining to establish reticulocyte maturity in bone marrow aspirates and peripheral blood. PMID- 1927186 TI - Multiple sampling to reduce inadequacy rates in stereotaxic aspiration cytology of the breast. PMID- 1927187 TI - Nomenclature for the cytodiagnosis of cervical intraepithelial lesions. PMID- 1927188 TI - Fine needle aspiration cytology of parapharyngeal meningioma. AB - A unique case of parapharyngeal meningioma identified on a tomographic scan and diagnosed preoperatively by fine needle aspiration (FNA) cytology is reported. The FNA smear showed the spindle-shaped cells in concentric whorls and scattered psammoma bodies that are characteristic of meningioma. The FNA diagnosis was subsequently confirmed on the excised specimen. The preoperative cytologic diagnosis was very helpful in planning the surgical removal of the tumor by a team of otolaryngologists and neurosurgeons. PMID- 1927189 TI - Cytodiagnosis of meningioma with atypical cytologic features. AB - The atypical cytomorphologic features present in intraoperative cytologic samples from two cases of meningioma are described. The important atypical cytologic features were slight nuclear hyperchromasia, cellular pleomorphism, anisokaryosis, frequent mitotic figures, nuclear grooves, occasional binucleations and a few intranuclear inclusions. The imprint smears from the case of atypical meningioma were cytologically diagnosed as showing atypical meningioma or sarcoma. The fine needle aspiration smears from the case histologically diagnosed as an angioblastic meningioma (meningeal hemangiopericytoma) showed more nuclear hyperchromasia and pleomorphism and were cytologically diagnosed as showing malignant meningioma. Atypical cytologic features in meningiomas may cause cytodiagnostic difficulties since other primary and metastatic meningeal tumors may show similar features; the main differential diagnostic possibilities are discussed. PMID- 1927190 TI - Reticulin fiber staining of crush preparations for the rapid differentiation between schwannomas and meningiomas. AB - The use of reticulin fiber staining of cytologic crush preparations for the rapid differentiation of schwannomas and meningiomas of the cerebellopontine angle was studied. As in paraffin-embedded sections, the reticulin stain demonstrated distinctly different patterns in the two types of tumors. Schwannomas showed extremely numerous, uniformly delicate straight fibers in a streaming or interlacing pattern in cellular areas and less dense, more wavy or curly fibers in degenerative areas. Fibroblastic meningiomas showed a few loose fibers of variable thickness in a root-like tangle while meningotheliomatous meningiomas showed no fibers, except in areas of fibrovascular stroma; both types showed small scattered round structures made up of reticulin fibers. These findings suggest that reticulin staining of crush preparations should be performed as an adjunct to routine cytologic staining of crush preparations and the study of frozen sections in making the intraoperative diagnosis of these tumors. PMID- 1927191 TI - Pulmonary metastases from intracranial meningioma diagnosed by aspiration biopsy cytology. AB - A case of rare extracranial metastasis from a recurrent intracranial meningioma is described. Incidentally discovered asymptomatic pulmonary metastases were diagnosed as meningioma by transthoracic fine needle aspiration (FNA) biopsy. The aspirate contained spindle-shaped tumor cells and other forms that seemed to correspond to the fibroblastic, syncytial and angioblastic areas seen in the histologic sections of the primary tumor. Cytomorphologically, metastatic meningioma appears to be sufficiently distinctive to permit its cytologic differentiation from other spindle-cell tumors. Although meningiomas metastasize rarely, this diagnosis should be considered in the interpretation of a transthoracic FNA biopsy of a pulmonary nodule or nodules in a patient with a history of recurrent intracranial meningioma, especially when the aspirate mainly consists of spindle-shaped neoplastic cells. PMID- 1927192 TI - Cytologic detection of malignant lymphoma cells with a hairy appearance in ascitic fluid. Report of a case with immunofluorocytometric analysis. AB - Neoplastic lymphocytes with a hairy appearance were detected in the ascitic fluid from a case of retroperitoneal malignant lymphoma. Although the tumor cells resembled those of hairy-cell leukemia (HCL), no leukemic change was observed, and the anatomic location of the neoplastic cells was different from that seen in HCL. The tumor cells were positive for some immunohistochemical markers of HCL (i.e., CD1 9 and SIg) but were negative for others (CD11c, CD25 and tartrate resistant acid phosphatase). Immunocytofluorometric and postmortem histologic studies showed the lesion to be a well-differentiated B-cell lymphocytic lymphoma with plasmocytic differentiation in some cells. PMID- 1927193 TI - The value of multiple preparations in the diagnosis of malignant pleural effusions. A cost-benefit analysis. AB - A cost-benefit analysis of five techniques employed in processing 108 malignant pleural effusions for cytopathologic examination was performed. Ethanol-fixed, Papanicolaou-stained smears were positive in 68% of the effusions, air-dried Diff Quik-stained smears in 66%, Cytospins in 83%, cell blocks in 85% and Millipore filters in 85%. Examination of one air-dried smear and one ethanol-fixed smear yielded a diagnostic sensitivity of 82%. Using a combination of two smears and one of three concentrating techniques (Cytospin, cell block or MIllipore filter) would have provided a diagnosis in over 90% of the effusions. The use of four or more preparations provided more sensitivity than did three preparations and decreased the likelihood that a malignant diagnosis would be based on the findings in only one preparation. The costs related to disposable materials and the College of American Pathologists (CAP) work load estimates for specimen preparation, staining and screening were compared. These data may be useful in developing optimal protocols for pleural effusion preparation in laboratories with specific work load requirements and limited resources. PMID- 1927194 TI - Cytology of angiosarcoma in effusions. AB - The cytologic and immunocytochemical findings in pleural effusions from three cases of angiosarcoma are presented. In two of the cases, the primary lesion was on the scalp; in the third case, an angiosarcoma of the small intestine developed after radiotherapy for Hodgkin's disease. Single malignant cells and small clusters of cells were seen in cytologic preparations from two cases while only single cells were seen in preparations from one case. The malignant cells had delicate, finely vacuolated cytoplasm with distinct borders. No specific morphologic features were noted. Immunoperoxidase studies revealed binding of Ulex europaeus and reactivity for vimentin in all three cases and expression of Factor VIII-related protein in two of the cases but no expression of epithelial markers. The clinical history and immunoperoxidase studies are necessary to distinguish angiosarcoma from metastatic adenocarcinoma and other malignancies in effusions. PMID- 1927195 TI - Blast transformation in chronic myeloid leukemia with synovial involvement. AB - In a patient with chronic myeloid leukemia in blastic transformation, the blast cells in a knee joint effusion were identical morphologically to those in the marrow. Cytochemical and immunocytochemical studies showed that these blasts were primitive erythroblasts and not granulocytic or monocytic precursors. The combined use of cytologic, cytochemical and immunocytochemical techniques will help to accurately identify cells in joint effusions and to elucidate the mechanism of synovial involvement by hematologic disorders. PMID- 1927196 TI - Preoperative fine needle aspiration cytology of a microcystic adenoma of the pancreas. AB - The preoperative fine needle aspiration (FNA) biopsy diagnosis of a microcystic adenoma of the pancreas is reported. Ultrasound examination and computed tomography showed a solid tumor in the pancreatic tail in a 68-year-old woman with abdominal discomfort. FNA biopsy of the lesion yielded a sample that contained only a few clusters of flattened ductal cells without criteria of malignancy. The presence of a considerable amount of watery fluid in the FNA sample was the main feature that suggested the diagnosis of a microcystic adenoma. This was confirmed by histologic study of the resected lesion. The differential diagnosis of microcystic adenoma is briefly discussed. PMID- 1927197 TI - Prospective comparison of the value of brushings before and after biopsy in the endoscopic diagnosis of gastroesophageal malignancy. AB - The hypothesis that the cytodiagnostic results on endoscopic brushings obtained before biopsy may be superior to those brushings obtained after biopsy, but with the accuracy of the subsequent biopsy reduced, was examined for 300 consecutive patients, including 256 with esophageal or gastric carcinomas. Following stratification by site and endoscopic appearance of their lesions, the patients were randomized to undergo brushing either before or after forceps biopsy. The accuracy of brushing cytology in patients with carcinoma was significantly higher when the brushing was performed before biopsy than after biopsy (93.5% versus 82.6%; P less than .01). The diagnostic yield of the biopsy was not significantly different whether the lesions were brushed before or after the biopsy (92.7% versus 93.2%; P less than .5). The diagnostic superiority of brushings obtained before biopsy did not relate to the site or endoscopic appearance of the tumor. There were no false-positive cytologic or histologic reports. For all 256 carcinomas, the cumulative accuracy (brushing cytology plus biopsy) reached 98.8% and was significantly better (P less than .001) than that of biopsy alone (93.9%) or cytology alone (87.9%). Apart from reinforcing the belief that the combined application of brushing and biopsy is mandatory for achieving optimal results, this study indicated that the brushing should be performed before the biopsy. PMID- 1927198 TI - Lipomatous lesions of the parotid gland. Potential pitfalls in fine needle aspiration biopsy diagnosis. AB - Nine cases of benign fatty tumors of the parotid studied initially by fine needle aspiration (FNA) biopsy and subsequently diagnosed by open biopsy were reviewed. All lesions presented as enlargements of the parotid gland. The cytologic diagnoses were correct in only five of the nine cases. While four of six FNA samples from lipomas were correctly diagnosed by cytology, the other two samples were classified as inadequate. Three cases of diffuse infiltration of the parotid by mature-appearing adipose tissue were cytologically characterized as "no diagnostic change" in two cases and sialosis in one case. The clinical, radiologic, cytologic and histologic features of these tumors are described to increase the familiarity of cytologists with these lesions, which may prevent unnecessary surgical intervention in some patients. PMID- 1927199 TI - Fine needle aspiration diagnosis of Penicillium marneffei infection. AB - A disseminated infection with Penicillium marneffei, a rare human pathogen that may infect both healthy and immunocompromised patients, was diagnosed by fine needle aspiration cytology in a patient infected with the human immunodeficiency virus. The presence of yeast-form organisms with an eccentric or central dot and occasional septate and elongated forms highly suggested the diagnosis, which was confirmed on culture. Establishment of the diagnosis is important because this infection is potentially curable. PMID- 1927200 TI - Fine needle aspiration biopsy diagnosis of a splenic metastasis from a papillary serous ovarian adenocarcinoma. AB - Abdominal computed tomography (CT) revealed an asymptomatic, solitary splenic mass in a woman who had undergone hysterectomy and bilateral salpingo oophorectomy for papillary serous ovarian adenocarcinoma four years previously. CT-guided fine needle aspiration (FNA) biopsy of the mass demonstrated the presence of nests of malignant epithelial cells in papillary structures. The FNA diagnosis of metastatic ovarian adenocarcinoma was confirmed by histologic study of the splenectomy specimen. Five years later, following several courses of chemotherapy, the patient was in apparent good health. This case again illustrates the value of FNA biopsy in diagnosing lesions in deeply situated organs, such as the spleen. PMID- 1927201 TI - Psammoma bodies in fine needle aspirates from thyroids containing nontoxic hyperplastic nodular goiters. AB - Psammoma bodies present in fine needle aspiration (FNA) smears with typical cytologic features of colloid goiter from five patients raised the possibility of coexistent papillary carcinoma. However, subsequent careful histologic examination of the entire thyroidectomy specimens did not show occult carcinoma in any of the cases. The psammoma bodies were identified in the stroma next to the foci of papillary hyperplasia in each case. They were small, often equal in size to or slightly larger than the follicular epithelial cell nuclei, and could be misinterpreted as epithelial cell nuclei. These findings suggest that the presence of psammoma bodies in an FNA smear cytologically consistent with a colloid goiter should raise the possibility of coexistent papillary hyperplasia or neoplasia. However, because of the strong statistical association of psammoma bodies with malignant thyroid neoplasms, histologic confirmation is mandatory in such cases. PMID- 1927202 TI - Fine needle aspiration cytodiagnosis of epidermoid cysts of the spleen. Report of two cases. AB - Fine needle aspirates of incidentally observed splenic cysts in two young women showed large numbers of squamous cells with pyknotic nuclei but no atypia, resulting in cytodiagnosis of epidermoid cysts of the spleen. This was confirmed in one case by immunocytochemical staining and histologic examination. The origin and differential diagnosis of epidermoid cysts of the spleen are briefly discussed. PMID- 1927203 TI - Fine needle aspiration diagnosis of pilomatrixoma. A monomorphic population of basaloid cells with squamous differentiation not to be mistaken for carcinoma. AB - In a case of pilomatrixoma, an initial fine needle aspiration (FNA) biopsy of a skin lesion yielded only a monomorphic population of mitotically active basaloid cells with squamous differentiation, without anucleated ghost cells, chronic inflammatory cells or foreign-body giant cells. These findings suggested a metastatic squamous-cell carcinoma or a malignant tumor of adnexal skin. The correct diagnosis was made by repeat FNA, which yielded the basaloid cells and ghost cells characteristics of pilomatrixoma; the FNA diagnosis was confirmed by subsequent excisional biopsy. This case demonstrates that pilomatrixoma should be considered in the differential diagnosis of skin aspirates that contain a dominant population of basaloid cells. The differentiation of pilomatrixoma from malignant lesions of the head and neck region is discussed. PMID- 1927204 TI - Nomenclature for the cytodiagnosis of cervical intraepithelial lesions. PMID- 1927205 TI - Comparing methods of cervical smear sampling. PMID- 1927206 TI - Cytologic findings in conjunctival samples obtained with a standard Cytobrush. PMID- 1927207 TI - An epidemiological approach to sexually transmitted diseases--with special reference to contact tracing and screening. AB - Sexually Transmitted Diseases (STD) are a major health problem all over the world. The diseases are often spread by unsuspecting asymptomatic individuals. One important means of controlling STD is thus the identification of asymptomatic persons. The purposes of this thesis were a) to describe methods of identifying infected individuals through contact tracing and screening, b) to evaluate contact tracing routines, c) to compare epidemiological characteristics of two different groups of chlamydia-infected women and their partners and d) to see if data from contact tracing could be used in a model describing partner choice and STD spread. A microepidemic of penicillinase-producing gonococci was effectively controlled through contact tracing by cooperating counsellors. Serotyping of gonococci and graphic description proved of great help in mapping the contact chain. Contact tracing integrated in the psychosocial long-term care of HIV infected patients resulted in identification of a great number of previously unidentified individuals. Screening for Chlamydia trachomatis (Ct) among asymptomatic patients of family planning clinics revealed a 7.3% Ct prevalence. Four factors were significantly correlated to the risk of being infected: age 18 23, duration of present relationship less than 1 year, failure to use condoms and no previous history of genital infection. Abstention from testing was especially high in areas with low socio-economic status. In these areas, increased resources for health care are needed. Five different levels of management of Ct infections were compared. Increased measures to verify that reported partners were examined decreased reinfections and after Ct was included in the STD Act more reported partners than before came for examination. Index patients found by chlamydia screening and their partners have a lower average number of recent partners than index patients visiting an STD clinic and their partners. Partners of female patients in the STD clinic group were also more often Ct-positive. The differences between the groups are small and do not justify different ambitions in partner management. Choice of steady partner was rather restricted and choice of casual partner followed a more random pattern. Our data thus do not support a pure random mixing model for STD spread. PMID- 1927208 TI - Quantitative monitoring of acute experimental cutaneous pain and inflammatory vascular reactions. Effect of local analgesics, capsaicin and antihistamines. PMID- 1927209 TI - Accumulation of DNA within chromocentres of terminally differentiating chick embryo chondrocytes. AB - Automated television (TV) densitometric technique which allows the recognition and recording of chromatin compartments was applied to the study of chromatin rearrangement during chondrogenesis. Genetically active chondroblasts and inactive definite chondrocytes of E7 chick cartilage model, stained on the imprints for DNA, were a subject for the comparative study. Large chromatin granules with constant morphometric parameters, displaying positive staining for C-heterochromatin and identified as chromocentres, were found to accumulate 30% of cellular DNA, doubling its concentration during chondrogenic maturation. A test for the DNA content ethalonization proved this to be due to redistribution of DNA from the euchromatinic compartment. PMID- 1927210 TI - Employment of merocyanine 540 fluorescence to form diaminobenzidine (DAB) oxidation product: a photoconversion method for the visualization of erythrocyte membrane fluidity for light and electron microscopy. AB - Intact native red blood cells (RBC) and treated RBC preparations were labelled with MC 540 and irradiated in the presence of diaminobenzidine (DAB). The polymerized diaminobenzidine reaction product is permanently stable in comparison with the labile fluorescence labelling. The brownish stained DAB polymerization product (DAB brown) and osmium black (after conversion of DAB brown with OsO4) allow the densitometrical determination with the light microscope. The latter product can be directly observed in the electron microscope. A direct correlation exists between the fluorescence intensity and the polymerized diaminobenzidine staining. It can be deduced that the enhancement of the DAB mediated contrast is reflecting an increased fluidity of the red cell membrane. The reaction was successful with all red cell preparations tested. This method is also suitable for the determination of fluidity changes in other cell membranes. PMID- 1927211 TI - Lectin histochemistry of the olfactory surface in two teleostean fishes. AB - A histochemical study on carbohydrate sequences in the epithelial surface of the olfactory organs in 2 teleostean species was carried out by means of lectins conjugated with peroxidase. At the same time, the distribution of the 2 kinds of epithelium are found, and the influence of decalcification with HNO3 in the pattern of reactivity to the lectins used were studied. The 2 components which reacted with the lectins were: 1. the apical surface of the olfactory epithelium, which was rich in L-mannose, N-acetyl-glucosamine, or sialic acid residues, and 2. the goblet cells which presented N-acetyl-glucosamine or sialic acid and N acetyl-galactosamine. In neither site were found residues of L-fucose. The non olfactory epithelium, where the goblet cells were located, showed signs of proceeding from a metaplasia of the olfactory epithelium. The decalcification in general terms supposed an intensification of the binding of the lectins to the tissues studied, and also the presence of new affinities which were not found without this treatment. In conclusion, the olfactory epithelium of these 2 teleostean fishes showed a rich layer of carbohydrates on its surface that is probably not only secreted by the goblet cells but also by the supporting cells. PMID- 1927212 TI - Differentiation dependent matrix formation (fibronectin and laminin) in an experimental murine rhabdomyosarcoma model. AB - Cellular differentiation processes along with formation of extracellular matrix proteins were investigated in methylcholanthrene-induced murine rhabdomyosarcomata. We used primary tumours, allotransplants in nude mice, and the respective tumour recurrences generated by repeated incomplete surgical tumour removal. The expression of the differentiation markers desmin and myoglobin as well as the presence of fibronectin and laminin was ascertained by immunohistochemical methods. The question arises, whether or not correlations between the grade of cellular differentiation (desmin, myoglobin) and extracellular matrix formation (fibronectin, laminin) exist in tumours with striated muscle cell differentiation. The constant relations between cellular differentiation and matrix formation in original tumours also applied to allotransplants and tumour recurrences in which partially modulations of differentiation in comparison with original tumours could be recognized. PMID- 1927214 TI - Nursing practice standards and competencies for nurses beginning to practice in Alberta. Alberta Association of Registered Nurses May 1991. PMID- 1927215 TI - Competencies for nurses beginning to practice in Alberta. Alberta Association of Registered Nurses, May 1991. PMID- 1927213 TI - Indium (III)-hematoxylin as a staining and contrasting agent for light and electron microscopy. AB - A deeply violet indium (III)-hematoxylin complex is formed when indium trichloride is added to an aqueous solution of oxidized hematoxylin. Treatment of glutaraldehyde fixed and Araldite embedded sections of rat seminiferous tubules with indium-hematoxylin revealed a definite staining and contrasting pattern. Semithin sections showed chromatin and nucleoli in violet-blue. Under the electron microscope, chromatin, nucleoli, ribosomes, synaptonemal complexes, chromatoid bodies, membranous components, and microtubules from sperm tails presented high electron opacity, while the acrosome and basement membrane appeared with a lower contrast. This performed indium-hematoxylin complex, which shows an absorption peak at lambda = 560 nm with shoulders at about lambda = 440 and 400 nm, could be valuable as a new staining and electron contrasting agent. PMID- 1927217 TI - Nursing models--a major step towards professional autonomy. PMID- 1927216 TI - Teaching breast self-examination in a rural community. PMID- 1927218 TI - The pre admission program. PMID- 1927219 TI - Management of the fluid balance in prevention and therapy of ARDS. PMID- 1927220 TI - Oxygen radicals and lung injury. AB - This article describes the formation of oxygen radicals and their biological effects, especially in relation to lung injury. Various recent experimental data are reviewed. The relationships between hydrostatic effects and permeability effects in producing injury and edema are stressed. Means of prevention and problems related to extrapolation to clinical situations are focused. PMID- 1927221 TI - Differential ventilation. PMID- 1927222 TI - Extracorporeal carbon dioxide removal performed with surface-heparinized equipment in patients with ARDS. AB - To avoid the drawbacks of systemic anticoagulation during prolonged extracorporeal circulation in patients with adult respiratory distress syndrome (ARDS) a heparinization technique has been developed by which partially degraded heparin can be covalently end-point attached to the surface of the equipment constituting the extracorporeal circuit (Carmeda Bio-Active Surface, CBAS) thereby localizing the anticoagulatory effect. Since 1986 we have used extracorporeal circuits and membrane lungs coated with the CBAS for extracorporeal lung assistance (ECLA) in 14 patients suffering from ARDS. The patients were on ECLA for 3 to 55 days with a survival rate of 43%. Our experience so far is that by using equipment coated with CBAS it is possible to perform long-term extracorporeal circulation with a minimum of intravenously administered heparin, thus avoiding the risk of major coagulation defects. PMID- 1927223 TI - Lung surfactant in respiratory distress syndrome. AB - Severe respiratory failure is always associated with a defect in the surfactant system. Surfactant substitution in newborn infants with respiratory distress syndrome (RDS) has gained worldwide acceptance. In the present study, we have evaluated whether surfactant diagnostics are of use in choosing recipients of exogenous surfactant. In addition, we studied whether factors apparently unrelated to surfactant influence the degree of respiratory failure and surfactant responsiveness. In small preterm infants, the surfactant indices in amniotic fluid (L/S ratio and phosphatidylglycerol), within 3 days of birth, predicted the risk of RDS with a sensitivity of 90-100%, and a specificity of 50 85%. The surfactant indices, measured in BAL, predicted the risk of ARDS (which became evident 1 to 7 days later) with a sensitivity of 50-60% and a specificity of 59-65%. In small preterm infants with RDS, the amount of fluids given during the first day correlated positively with the degree of respiratory failure and negatively with the degree of surfactant responsiveness. According to an experimental study, in hydrostatic lung edema, exogenous surfactant is diluted by edema fluid and becomes sensitive to inhibitors of surfactant function. Beside dosage, quality, and time of administration, the management of patients largely dictates the responsiveness to exogenous surfactant. PMID- 1927224 TI - Surfactant inactivation and surfactant replacement in experimental models of ARDS. AB - Lung structure and function, and the effect of surfactant replacement, were studied in three animal models of adult respiratory distress syndrome (ARDS): surfactant depletion by repeated lung lavage, proteinaceous pulmonary edema induced by prolonged exposure to hyperoxia, and inoculation with hybridoma making an antibody to the hydrophobic surfactant-associated protein, SP-B. Surfactant replacement therapy restored normal gas exchange in respiratory failure induced by repeated lung lavage but was ineffective in animals with severe lung parenchymal lesions induced by hyperoxia or antibody to SP-B. Lung edema fluid from animals exposed to hyperoxia inhibited surfactant function in a concentration-dependent manner. These observations indicate that, in experimental ARDS, the effect of surfactant replacement depends on the type of animal model and, especially, on the degree of lung injury present at the time of therapy. PMID- 1927225 TI - Mechanics of the respiratory system in ARDS. PMID- 1927226 TI - Does mechanical ventilation damage the lung? PMID- 1927227 TI - Hypoxic pulmonary vasoconstriction in the adult respiratory distress syndrome. AB - Increased pulmonary vascular resistance (PVR) and microvascular hyperpermeability resulting in lung edema and arterial hypoxemia are mainstays in the development of adult respiratory distress syndrome (ARDS). The proposed pathophysiologic mechanisms include activation of complement and polymorphonuclear leukocytes secreting lysosomal enzymes, toxic oxygen metabolites (TOM) and eicosanoids. Platelets and coagulation factors are also involved, and in the most severe cases even monocytes are activated as reflected in release of thromboplastin. The latter may elicit disseminated intravascular coagulation (DIC). Under physiologic conditions lung blood flow is diverted from poorly to better oxygenated areas by way of hypoxic pulmonary vasoconstriction (HPV), thereby counteracting a decrease in arterial oxygenation. Many vasoactive substances have been proposed and again refuted as possible mediators of HPV. In this study we have focused on the following: histamine, catecholamines, arachidonates, calcium, phosphoinositides and TOM as well as endothelium-derived relaxing and constricting factors. Whether HPV is present in ARDS and whether it is advantageous or not seems to depend on the stage and extent of disease. We discuss possible interactions between HPV and ARDS mediators and between HPV and various vasoactive agents tested for therapeutic effects. Out of the abundance of mediators released, prostacyclin, prostaglandin E1, activated complement and platelet activating factor have been shown explicitly to inhibit HPV whereas others are suspected of doing so. In therapeutical use, prostacyclin has proved to reduce PVR and at the same time enhance cardiac output and oxygen delivery. In mild to moderate ARDS, improvement of arterial oxygenation has also been obtained employing almitrine bismesylate, a potentiator of HPV. Experimentally, adenosine effectively reduces increments in PVR and microvascular permeability with modest effects on systemic circulation. However, further investigations are warranted to decide whether adenosine or more specific blockers as, for instance, monoclonal antibodies against tumor necrosis factor should be integrated in ARDS therapy in the future. PMID- 1927228 TI - Lung lymph drainage. AB - This presentation was intended as a brief review of two principally different approaches to studies on pulmonary lymphatic drainage. When selecting an experimental model, we have to choose between either sampling of pure lung lymph thereby sacrificing information about whole organ fluid balance, or emphasize dynamic fluid balance for the whole lung at the expense of obtaining pure lung lymph. Both approaches can be seen as fruitful and complementary strategies to obtain relevant information on pulmonary pathophysiology. PMID- 1927229 TI - Disseminated intravascular coagulation. AB - This review encompasses a description of the main pathophysiological events leading to disseminated intravascular coagulation (DIC). Emphasis has been put on microcirculatory disturbances and endothelial dysfunction. The normal hemostatic functions of the vascular endothelium are described. The close connection between endothelium and superimposed immuno-modulators is stressed as is the interrelation between the proteolytic cascade systems in the blood. The importance of differentiating local and systemic events is discussed. Organ dysfunction in multiple organ failure (MOF) is exemplified by pulmonary insufficiency in the adult respiratory distress syndrome (ARDS). Essential laboratory tests of DIC are described as are the cornerstones of treatment. PMID- 1927230 TI - Actions and interactions of mediator systems and mediators in the pathogenesis of ARDS and multiorgan failure. AB - A great variety of mediators and mediator systems are involved in the disturbance of the microcirculation and vascular permeability following polytrauma and sepsis. The locally accentuated, organ related activation and the cooperation of several of these mediators and mediator systems over a longer period of time seem to be responsible for the development of an acute organ failure in terms of ARDS and MOF. Cytokines from macrophages seem to be the determining factors converting a primarily functional and reversible systemic vascular reaction into organ related morphological lesions. This pathogenetic complexity has to be considered in future concepts for therapy and prophylaxis with regard to the hierarchical rank of the mediators involved. PMID- 1927231 TI - Right ventricular function during ARDS. PMID- 1927232 TI - Measurement of extravascular lung water--methods and clinical implications. AB - The estimation of changes in extravascular lung water during different experimental and clinical conditions forms an intriguing field of research. Present methods for the measurement of lung water are difficult to apply in day to-day clinical practice. Most methods are not only low in accuracy and sensitivity but are also invasive. A new indicator-dilution technique using heavy water and indocyanine green as diffusible and nondiffusible indicators, respectively, may provide us with a new investigative method for longterm bedside estimation of lung water. PMID- 1927233 TI - CT scan in ARDS: clinical and physiopathological insights. PMID- 1927234 TI - Radiospirometry V/Q. AB - Single photon emission computerized tomography (SPECT) of the lungs was used for topographical determination of V/Q ratios in anaesthetized-paralyzed subjects. Ventilation and perfusion were estimated from the distribution of an inhaled aerosol containing a radioactive isotope and injected macroaggregates of human albumin tagged with another isotope. There was a prominent gradient of V/Q ratios in the vertical direction. In the horizontal plane there were marked gradients of both ventilation and perfusion of similar appearance with maxima in central lung regions, resulting in only small gradients of V/Q ratios. PMID- 1927235 TI - Midazolam and amnesia in pediatric premedication. AB - One hundred and twenty-eight children aged three to ten years, were studied to determine the effect of premedication on amnesia for the preanesthetic period. Four comparable groups were used: A control group, no premedication; oral trimeprazine tartrate 2 mg/kg, methadone 0.1 mg/kg plus droperidol 0.15 mg/kg (T.M.D.); oral midazolam 0.45 mg/kg; intramuscular midazolam 0.15 mg/kg. Amnesia was tested for four pictorial facts, and for induction of anesthesia. For pictorial facts, both routes of midazolam administration gave a sixty percent incidence of amnesia compared with sixteen percent in the control group (p less than 0.001). The T.M.D. premedication provided a forty-three percent incidence, also better than the control group (p less than 0.05). Induction was remembered by fifty percent of the midazolam children compared with sixty-six percent of the T.M.D. group (p greater than 0.05) and eight-one percent of the control group (p less than 0.05). The potential advantages of amnesia in pediatric premedication are discussed. PMID- 1927236 TI - Tranexamic acid in the treatment of anaphylactic shock. AB - We report the case of a patient with multiple trauma who developed pronounced anaphylactic shock, and was successfully treated with 1000 mg tranexamic acid intravenously (Exacyl). This antifibrinolytic agent is also a potent inhibitor of the complement system and its use for the prevention and treatment of anaphylactic or anaphylactoid shock is discussed. PMID- 1927237 TI - Entrapment of a Swan-Ganz-catheter in tricuspidal valve. AB - Unsuccessful pulmonary artery catheter removal is a rare but potential life threatening complication. This was observed in a dog during investigations on cerebrovascular reactivity. Postmortem examination showed entrappment of the pulmonary artery catheter in tricuspidal valve. "Clinical" symptoms are described and therapeutic measures in the case of suspected entrappment are discussed. PMID- 1927238 TI - The effects of a single oral dose of lorazepam and alprazolam on reaction times in young healthy volunteers. AB - Lorazepam (Temesta) and alprazolam (Xanax) are two benzodiazepines which are widely used for their anxiolytic activity. In this study their effect on psychomotor functions was investigated. Eight young healthy volunteers participated in the experiments. Using a double-blind cross-over design, the effect of single oral doses of lorazepam (2.5 mg) and alprazolam (0.5 mg) on a choice reaction time test to visual stimuli (letter pairs presented on a computer screen), were assessed. The experimental procedure consisted of three sessions which differed from each other either by the stimulus presentation rate, or by the presence or absence of a warning signal. In all three sessions, lorazepam, when compared with placebo, significantly prolonged the reaction times (RT), while alprazolam did not. Increasing the interstimulus interval resulted in an equal increase of the reaction times in the three conditions. On the other hand, the introduction of a warning signal which preceded the presentation of the letter pairs, improved performance in the three conditions. This improvement was more pronounced after lorazepam than after placebo. This finding is interpreted as a partial recuperative effect for the impaired performance in the baseline condition after intake of lorazepam. PMID- 1927239 TI - Postoperative P.C.A. in abdominal surgery. Analysis of 200 consecutive patients. AB - Patient-Controlled-Analgesia (PCA) is becoming a standard in post-operative analgesia. This prospective study was designed to get more information on the safety and the efficiency of morphine PCA following abdominal surgery. Two hundred patients were enrroled Morphine requirements, number of unsatisfied demands, patients' satisfaction and side effects were recorded for 36 hours postoperatively. The mean morphine requirement was 23.2 mg for the first 12 hours, 22.2 mg for the next 12 hours and 16 mg for the last 12 hours. Female patients required significantly less morphine than male. Interestingly such difference was no more present for patients older than 60 years. The larger the morphine bolus dose, the greater the total amount needed without any better analgesia. A bolus dose of 1 mg seemed to be the best to be recommended. The variability in the number of unsatisfied demands (i.e. demands during the lockout interval) was quite large. The number of unsatisfied demands was not influenced by the size of the bolus dose. The patients' satisfaction was high: 60% enthusiastic, 36% satisfying, 4% negative. There was no difference in satisfaction linked to gender. On the other hand, a history of a previous surgery experience without PCA raised patients' satisfaction score. Side effects were uncommon. It is concluded that morphine PCA is an efficient and safe technique of post-operative analgesia in abdominal surgery. PMID- 1927240 TI - Fentanyl in 2% mepivacaine compared with fentanyl in 0.5% bupivacaine: two parallel controlled double blind studies. AB - The efficacy of epidural mepivacaine and bupivacaine, combined with fentanyl to enhance blockade, was compared in two parallel controlled, double-blind clinical trials. Patients in the studies (n = 91) were scheduled for orthopedic surgery of the legs and a tourniquet was used in all cases. Those patients receiving mepivacaine attended day surgery only, whereas patients receiving bupivacaine were hospitalised. Epidural puncture was performed with a Tuohy needle at the L3 4 level in the lateral decubitus position. Levels of sensory and motor blockade were assessed; adverse reactions and pain during surgery were recorded. There were four groups of patients: 1) 26 received 2% mepivacaine with placebo; 2) 26 received 2% mepivacaine with 0.1 mg fentanyl; 3) 19 received 0.5% bupivacaine with placebo and 4) 20 patients received 0.5% bupivacaine with 0.1 mg fentanyl. The levels of the sensory blockade was comparable in all groups. The degree of motor-blockade was more intense in the mepivacaine groups, but the blockade by mepivacaine lasted shorter. Addition of fentanyl did not change the sensory and motor blockade. Intraoperative pain was reported by: 7 patients in the mepivacaine/placebo group; 4 patients in the mepivacaine/fentanyl group; 4 patients in the bupivacaine/placebo group; and by one patient in the bupivacaine/fentanyl group. These results indicate that fentanyl enhances the quality of epidural blockade when combined with either mepivacaine or bupivacaine. PMID- 1927242 TI - Electron-microscopic studies on the maturation of secretory cells in the mouse Harderian gland. AB - The porphyrins in the Harderian glands of mice are first detectable at 7-8 days of age in both sexes. Thereafter, the levels show a marked rise during the closed eye period, reaching a peak around the time of eyelid disjunction and then decrease gradually until day 25. At onset of puberty, the level rises again and exhibits a sexual dimorphism. The development of the Harderian gland was examined by light and electron microscopy in the mouse. Although two types of secretory cells, designated as type A and type B, comprise the glandular epithelium in fully developed glands, the time of neonatal appearance is different between the two. Type A cells first appear on the 5th day of age, while type B cells appear around the 7th day corresponding to the time at which porphyrins are first detected. Results of the investigations suggest that the porphyrins in the Harderian gland of mice may be synthesized mainly by type B cells. PMID- 1927241 TI - Influence of muscle shortening on the geometry of gastrocnemius medialis muscle of the rat. AB - For static and dynamic conditions muscle geometry of the musculus gastrocnemius medialis of the rat was compared at different muscle lengths. The dynamic conditions differed with respect to isokinetic shortening velocity (25, 50 and 75 mm/s) of the muscle-tendon complex and in constancy of force (isotonic) and velocity (isokinetic) during shortening. Muscle geometry was characterized by fibre length and angle as well as aponeurosis length and angle. At high isokinetic shortening velocities (50 and 75 mm/s) small differences in geometry were found with respect to isometric conditions: aponeurosis lengths differed maximally by -2%, fibre length only showed a significant increase (+3.2%) at the highest shortening velocity. The isotonic condition only yielded significant differences of fibre angle (-4.5%) in comparison with isometric conditions. No significant differences of muscle geometry were found when comparing isotonic with isokinetic conditions of similar shortening velocity. The small differences of geometry between isometric and dynamic conditions are presumably due to the lower muscle force in the dynamic condition and the elastic behaviour of the aponeurosis. It is concluded that, unless very high velocities of shortening are used, the relationship between muscle geometry and muscle length in the isometric condition may be used to describe muscle geometry in the dynamic condition. PMID- 1927243 TI - [Manual examination of so-called lumbosacral instability]. AB - By the manual test of the lumbosacral instability described by Eder and Tilscher we can never find out for certain whether the fifth lumbar vertebra can be shifted ventrally above the sacrum. Before this test the patient has to be turned over on to his side with hips flexed, which causes a ventral flexion (anteflexion) of the lumbosacral segment. During the test, however, the lumbosacral segment is forced to a dorsal flexion (retroflexion); therefore the spinous process of the fifth lumbar vertebra retires from the back surface simulating a sliding forward of the whole vertebra. PMID- 1927244 TI - Lymphatic vessels in the healthy human dental pulp. AB - The lymphatic vessels of the dental pulp have been studied in non-carious teeth of young people. A network of lymphatic vessels drains the pulpal tissue. The lymphatic capillaries are characterized by a thin wall with an irregular profile. Cellular projections rise from the endothelial cells. Micropinocytotic vesicles and intercellular adjoining structures are the main mechanisms for the lymph formation. Multivesicular structures, Weibel-Palade bodies and paracrystalline inclusions have been observed. PMID- 1927245 TI - Ultrastructural study on the retinal pigment epithelium of human embryos, with special reference to quantitative study on the development of melanin granules. AB - The development of the retinal pigment epithelium (RPE) was studied ultrastructurally, using 13 externally normal human embryos, Carnegie stages ranging from 13 to 23 (4-8 week of gestation). Melanosomes in the peripheral and posterior RPE were classified according to Fitzpatrick et al. The melanosome of phase I is formed from the Golgi complex and parcelled off into small vesicles. The vesicle enlarges and elongates to form an oval organelle with membranous structures in it (phase II melanosome). Subsequently, melanin deposits on the membranous structures of the melanosomes (phase III melanosomes), and the completion of this process produces a uniformly electrondense granule without discernible internal structures (phase IV melanosome). Melanosomes of phases III and IV appeared in the RPE at stage 15. As the embryonic stage advanced, the ratio of phase II melanosomes decreased and that of phase IV melanosomes increased. The number of phase III melanosomes reached a peak in the peripheral and posterior RPE at stages 15 and 18, respectively. After stage 17, the increase in melanosomes and intracellular organelles was more prominent in the posterior than in the peripheral RPE. During stages 13 and 15, gap junctions were present not only in the apical but also basal plasma membranes of the RPE. At stage 20, gap junctions in the basal plasma membrane disappeared except for the transitional areas from the RPE to the neural retina (NR). In addition, gap junctions were observed between NR and RPE only in the peripheral region at stage 20. The morphological and quantitative differences in the peripheral and posterior RPE in the embryonic period are discussed. PMID- 1927246 TI - Electron probe X-ray microanalysis of calcium and phosphorus distribution in developing hamster tooth germs in vitro and in vivo. AB - The aim of the present study was to investigate the spatial distribution of Ca and P in dentin and enamel of developing first (M1) and second (M2) maxillary hamster molars (age: 3-5 days) in comparison with cultured molars. For culturing the germs were dissected from 3-day-old hamsters and incubated for 1 and 2 days, respectively, in a modified BGJb medium. Electron probe X-ray measurements were carried out on 3 regions extending in a vertical axis from cusp tip over cusp middle to cusp base next to the cervical loop region. Neither the in vivo nor the in vitro group was statistically different in the Ca and P concentration in the regions of dentin. In both groups the measurements in enamel showed a gradient with an increase in Ca and P from enamel surface towards dentin-enamel junction and a gradient with an increase from cusp base towards cusp tip. Direct comparison of the in vivo group with the in vitro group did not demonstrate a statistical difference between the mineral content of the 4-day-old germs and the 1-day culture germs, respectively the 5-day-old germs and the 2-day culture germs. The results indicate a high correspondence between the mineralization process of in vitro and in vivo tooth germ development. PMID- 1927247 TI - Origin of the water-clear cell in the parathyroid gland of the golden hamster. AB - Water-clear cells and transitional forms between the chief cells and water-clear cells were observed in the parathyroid gland of the golden hamster. Their ultrastructure is described, and the origin of the water-clear cell is discussed. PMID- 1927248 TI - Effects of N-methyl-N'-nitro-N-nitrosoguanidine and deoxycholic acid on processes of tumorous transformation of rat visceral yolk sac. In vitro and in vivo studies. AB - The possibility to use the rat visceral yolk sac as a model for the study of processes of cell transformation was studied. Yolk sac teratocarcinomas could be induced using the method of in vitro culture of yolk sacs in a medium containing a direct carcinogen and a tumor promoter with subsequent transplantation under the renal or testicular capsule of syngeneic rats. Biochemical, electron microscopic and immunohistochemical methods were used to study the characteristic changes that accompanied cellular transformation. It was shown that even a short term (3 h) exposure of the yolk sac cells to N-methyl-N'-nitro-N-nitrosoguanidine with or without deoxycholic acid in vitro decreased significantly the rate of yolk sac transport and changed their developmental potential with manifestation of carcinogenic antigens (polyclonal keratins, monoclonal vimentin and smooth muscle actin). This cancerous transformation was promoted following their in vivo transplantation into special anatomic sites. PMID- 1927249 TI - Course of the arteria vertebralis in its segment V1 from the origin to its entry into the foramen processus transversi. AB - The segment V1 of the arteria vertebralis (pathway from its origin from the a. subclavia to the entry into the respective foramen processus transversi) has a special significance in vascular surgery. Contrary to indications in the literature, we found 47.15% of the specimens to have a contorted course in this segment. The tortuosities carried by the respective vessels were found to be horizontal in 42.5%, in a sagittal direction in 30% and in the frontal plane in 27% of the cases. However, no significant difference was found between vessels carrying a tortuosity and those without, regarding the average lengths of the arteries concerned in the segment V1. PMID- 1927250 TI - Ultrastructural studies on the effects of hypergravity environment on the parathyroid glands in golden hamsters of different ages. AB - The ultrastructure of the parathyroid glands of infantile, young, adult and senile golden hamsters subjected to a hypergravity environment was studied. In the parathyroid glands of 5-, 10- and 20-day-old, and 1- and 3-month-old golden hamsters exposed to a hypergravity environment, the Golgi complexes were significantly increased, and in 5-, 10- and 20-day-old, and 1- and 8-month-old animals exposed to a hypergravity environment, the cisternae of the granular endoplasmic reticulum appeared to be increased as compared to those of each control group. In addition, in centrifuged animals numerous prosecretory granules were observed in the Golgi areas, and many secretory granules were located in the peripheral cytoplasm. The ultrastructure of the parathyroid glands of 14-month old centrifuged animals resembled that of 14-month-old control animals. These results suggest that the secretory activity of the parathyroid gland may be stimulated in infantile, young and adult golden hamsters subjected to a hypergravity environment and may not be stimulated in senile animals subjected to a hypergravity environment. PMID- 1927251 TI - Presurgical evaluation of patients with intractable partial epilepsy: the Dutch epilepsy surgery program. PMID- 1927252 TI - Meningoencephalitis and meningitis due to an adenovirus type 5 in two immunocompetent adults. AB - Two unrelated patients, previously in good health, were admitted to hospital in the course of the same week, one for meningoencephalitis and the other for meningitis. In both of them, an adenovirus type 5 was cultivated on the cerebrospinal fluid. The evolution was benign in both cases. No similar observation has been found in the literature. PMID- 1927253 TI - Singlet oxygen induced cerebral vasospasm: an experimental study in rats. AB - A new experimental model is described which can be used as an alternative to study the effects of subarachnoid hemorrhage (SAH) in rats. Vasospasm of the basilar artery is induced photochemically after transpalatal illumination of intracisternally injected rose bengal in two different rat strains. Singlet oxygen, generated in the subarachnoid space, elicits vasospasm which has been demonstrated angiographically at 90 min and 24 h after photosensitisation. Sprague Dawley rats responded better than Wistar rats. Dilution of rose bengal in water was more vasospastic than dilution of rose bengal in artificial CSF. Since the action of singlet oxygen is similar to that of free radicals, this experiment gives an argument for the hypothesis that free radicals play a leading role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. PMID- 1927254 TI - Amantadine hydrochloride for refractory generalized epilepsy in adults. AB - Amantadine hydrochloride has been shown in several open studies to benefit children with refractory generalized epilepsy. We used amantadine as adjunctive therapy in 10 adolescents and adults with generalized tonic-clonic, myoclonic, or absence seizures refractory to therapeutic levels of valproate, carbamazepine, phenytoin, and benzodiazepines. Seven patients were men and 3 were women aged 18 29 years, and 8 of 10 patients were mentally retarded. All patients had generalized epileptiform paroxysms on EEG, with generalized or absence seizure recorded in 9. Five patients had both absence and tonic-clonic seizures, and 2 had all three seizure types. Amantadine was added to the existing regimens in weekly increments to 400 mg/day. Two patients had greater than 90 per cent seizure reduction, both with vomiting and somnolence. Two patients had seizure reduction between 50 and 90 per cent, 1 with anorexia and sleepiness. Three patients had no change in seizures, and 3 had worse tonic-clonic seizures. Amantadine may have some antiepileptic efficacy of unknown mechanism, but it may worsen generalized tonic-clonic seizures and is likely to be of limited value in adults. PMID- 1927255 TI - Fatal Streptococcus suis meningitis in man. AB - A case of Streptococcus suis meningitis is observed in a 39-year-old and previously healthy meat factory worker. Neurological recovery was incomplete despite adequate and sustained antimicrobial therapy. Early deafness was demonstrated by brainstem auditory evoked potentials. Death due to aspiration pneumonia, cardiac arrest and subsequent cerebral anoxia occurred late in the course of the illness. PMID- 1927256 TI - Dexamethasone suppression test in depressive stroke patients. AB - Depressive psychiatric patients often shown non-suppression to the dexamethasone suppression test (DST). Stroke patients shows a high frequency of depression. In the present study the DST was studied in 76 stroke patients and 26 controls. No difference was found in frequency of non-suppression to the DST between depressive and non-depressive stroke patients. It was found that postdexamethasone plasma cortisol level at 08 a.m. was significantly higher in patient with the lesion in the right hemisphere compared to patients with the lesion in the left hemisphere. PMID- 1927257 TI - Memory loss due to transient hypoperfusion in the medial temporal lobes including hippocampus. AB - A typical case of transient global amnesia (TGA) was investigated with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) with 1.5-tesler scans. During the amnesic episode, a marked decrease of cerebral blood flow was observed in the areas confined to the territory of the bilateral posterior cerebral arteries including the hippocampus. After the episode, cerebral blood flow returned to normal and a circumscribed lesion was detected in the middle portion of CA 1 field of the left hippocampus. The SPECT findings prove direct evidence that the medial temporal structures are involved in the establishment of new memories, as well as in process of recalling only recently acquired memories, but not in retrieval of memories acquired long ago. The MRI findings indicate that a unilateral partial damage to CA 1 sector of the hippocampus does not develop a definite memory impairment and that high resolution MRI study on the hippocampus is necessary in TGA patients. PMID- 1927259 TI - Effectiveness of steroid treatment in myasthenia gravis: a retrospective study. AB - The records of 142 patients with generalized autoimmune myasthenia gravis who had been treated with steroids as the single immunosuppressive agent, collected at regular intervals, were employed for a retrospective evaluation. The effectiveness of treatment was assessed after 24 months; the data from the 6th and 12th months were also considered. After 24 months, 63.4% of the whole sample had improved (33.8% were in clinical or pharmacological remission); 13.4% were unchanged or had worsened and 22.3% had moved to a different immunosuppressive treatment. The rate of positive outcome was higher in patients over the age of 40 at disease onset. PMID- 1927258 TI - CT, somatosensory and brainstem auditory evoked potentials in the early prediction of functional outcome in putaminal hemorrhage. AB - The CT and median somatosensory and brainstem auditory evoked potentials (SEP and BAEP) were studied in 80 patients with spontaneous putaminal hemorrhage for their values in the early prediction of functional outcome. The CT scan was performed within 2 days and EPs within a week after the onset of symptoms. The activities of daily living was assessed at 6 months. Patients with good functional recovery had the following findings: 1) the hemorrhage had not involved the thalamus or the posterior limb of the internal capsule; 2) the SEPs were normal or had prolonged central conduction time; and 3) the BAEP was normal. When the cortical SEPs were absent, the majority of patients were moderately or severely disabled. Attenuation or absence of BAEP wave V always forecast a grave prognosis. It is concluded that the combined use of CT, SEP and BAEP is an objective and reliable method for the early prediction of functional outcome in patients with putaminal hemorrhage. PMID- 1927260 TI - Trends and survival for AIDS patients presenting with indicative neurologic diseases. AB - Nervous system involvement in patients with AIDS is frequent either due to direct infection by the HIV-1 or to opportunistic infections or neoplasms. In the present study we evaluate the epidemiologic characteristics of patients in whom the first AIDS manifestation was an indicative neurologic disease (IND) and the influence of such a presenting form in the patients' survival. Out of 1250 reported cases, 252 (20.2%) presented with one of the INDs, according with the CDC AIDS definition criteria. Neither sex nor age differences were found between patients presenting with and without an IND. IVDUs were more likely to present with an IND than homosexual/bisexual men (p = 0.024). Cerebral toxoplasmosis (CT) was the only IND with a significant proportional increase over time. Although some of the IND have a specific treatment, as a whole patients presenting with an IND lived shorter than those presenting with any of the other indicative disorders (p less than 0.0001). The incidence of IND is greater than elsewhere, mainly because of CT. The increment of CT may be in part due to the introduction of the new AIDS definition criteria. PMID- 1927261 TI - Hemitonic seizures: etiological and diagnostic considerations. AB - Intermittent unilateral tonic posturing of the limbs may relate to focal motor epilepsy, intermittent dystonia or hysteria, and diagnosis may be difficult. Five patients are presented who illustrate two distinct hemitonic syndromes which we believe to be epileptic, namely forced elevation of one arm and paroxysmal hemispasm. It is suggested that these attacks follow an irritative lesion involving the supplementary motor cortex and a deep lesion involving striatothalamic projections respectively. Brevity of episodes, their stereotyped nature and rapid response to anticonvulsant drugs supports an epileptic etiology. The term paroxysmal hemidystonia may not be appropriate for patients with intermittent stereotyped disorders of limb posture, where the clinical features support an epileptic basis and we suggest the designation hemitonic seizures. PMID- 1927262 TI - Serum interleukin-2 levels in patients with dementia of the Alzheimer type. AB - We examined serum interleukin 2 (IL-2) levels in 127 normal subjects and 22 patients with dementia of the Alzheimer type (DAT) using the enzyme-linked immunosorbent assay technique. There was no significant correlation between serum IL-2 levels and age. However, serum IL-2 levels in elderly normal subjects (older than 70 years of age) were significantly lower than in the younger normal subjects (younger than 30 years of age) (p less than 0.05). There were no significant differences in serum IL-2 levels between the patients with DAT and the age-matched normal controls. These results suggest that the changes of serum IL-2 levels in patients with DAT may be natural in the normal aging process. PMID- 1927263 TI - Sjogren's syndrome in patients with multiple sclerosis. AB - Twenty female patients with clinically multiple sclerosis were evaluated with regard to a possible underlying Sjogren syndrome. Two patients (10%) demonstrated a clinical Sjogren syndrome which does not differ significantly from the prevalence in an unselected population. Dry eye-symptoms occurred among MS patients and should be subjected to relevant diagnostic procedures. PMID- 1927264 TI - Effects of withdrawal of antiparkinson medication on gait and clinical score in the Parkinson patient. AB - Objective testing of medication is needed in Parkinson's disease. Gait analysis and clinical evaluation were done before and after a 24-h withdrawal of Parkinson medication. Twelve patients with stable, mild to moderate idiopathic parkinsonism (Hoehn and Yahr 1-3; seven men and five women mean age 59.9 years, mean duration of disease 6 years) were tested with gait analysis walking in five different paces. Velocity of gait, stride length and stride frequency, as well as stride length at constant velocity were calculated. Regression coefficients for the relation between stride length and stride frequency were also calculated. Clinical scoring according to the Webster rating scale and Hoehn and Yahr were performed for each test. Clinical functional assessment with a specially designed rise and gait test, an arm cycle test and the wooden rods test were done. Evaluated clinical score increased significantly (p less than 0.05) using both clinical tests. Maximum gait velocity (p less than 0.01), stride length at max. velocity (p less than 0.01), and stride length at constant velocity (p less than 0.03) were significantly decreased without medication. Stride frequency did not change. In the functional assessment tests only performance on the arm cycle test (p less than 0.03) was less well performed without medication. There was correlation between clinical score, gait and clinical functional assessment. The methods used detected significant changes in variables of gait as well as clinical scoring and some of the clinical functional assessments when medication was withdrawn for a 24-h period. The methods were useful in evaluation of pharmacological treatment. PMID- 1927265 TI - Anorectal ergotism. Induced by migraine therapy. AB - The current report describes 15 patients, 14 women and one man, in whom anorectal ulceration appeared after use of ergotamine suppositories. In seven cases there was only ulceration to be seen, whereas in eight anovaginal or rectovaginal fistulae were visible. Symptoms are not specific. In the majority of situations, ulceration can usually be treated successfully by immediate withdrawal alone. In one case a stenosis of the anal canal remained. Fistulae need surgical intervention. Two fistulae could be treated sufficiently by the local flap technique. In six cases a colostomy was needed, which was transient in five and permanent in one patient. One recurrence was seen after continued ergot-abuse. Dosage is not in direct correlation to ulceration. PMID- 1927266 TI - Blood-brain barrier permeability to micromolecules and edema formation in the early phase of incomplete continuous ischemia. AB - The distribution patterns of ionic Lanthanum (La3+; mol. wt. 139) were evaluated after 15, 30 and 60 min of middle cerebral artery occlusion in perfused-fixed rats. Blood-brain barrier (BBB) permeability to Evans blue (EB) and horseradish peroxidase (HRP; mol. wt. 40,000) in vivo was also evaluated. Brain tissue specific gravity was measured. An increase in brain water content was found as early as 30 min following occlusion. HRP and EB extravasation was not observed. La3+ crossed the interendothelial clefts of venules and capillaries at 30 and 60 min and was seen in both extracellular and intracellular brain compartments at 60 min. La3+ extravasation was seen in nonedematous areas bordering the regions of water accumulation. Our findings suggest that the early phase of incomplete continuous ischemia is accompanied by changes in BBB permeability and the interendothelial clefts of venules and capillaries seem to represent one of the early sites of ischemic damage. PMID- 1927267 TI - The relationship between plasma protein extravasation and remote tissue changes after experimental brain infarction. AB - Extravasated endogenous serum albumin and fibrinogen were identified immunohistochemically in coronal brain sections from normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) after permanent ligation of the right middle cerebral artery. Infarcts were seen in all the SHR but only in 6 out of 14 WKY. Six hours after ligation, extravasated proteins were located primarily within the borders of the infarcts whereas after 24 h and later there was an increasing spread in the white matter. After 7 days, a protein immunoreactivity was seen far outside the infarcted areas, mainly in the white matter and occasionally extending somewhat into the contralateral side. Three weeks after permanent ligation, the immunoreactivity for plasma proteins had a similar extension but was less intense than after 7 days. A gliosis was noted within the protein-positive regions. From 72 h and onwards the immunoreactivity for albumin but not for fibrinogen extended via the white matter into the ipsilateral thalamic nuclei, where marked, mainly cytolytic nerve cell damage and gliosis was found. The close spatial correlation with albumin immunopositivity and the histological features of the thalamic lesions indicate that the propagation of extravasated plasma constituents or degradation products from the infarct may influence the character, timing and extent of remote tissue changes after cerebral infarction. PMID- 1927268 TI - Comprehensive lectin histochemistry of normal and neoplastic human choroid plexus cells: alternation of lectin-binding patterns through neoplastic transformation. AB - Lectin histochemistry of the normal and neoplastic human choroid plexus cells [six choroid plexus papillomas (CPPs) and three choroid plexus carcinomas (CPCs)] was performed using eight representative lectins to study the development of sugar chain structures and also to determine whether lectins were useful for a histopathological diagnosis of choroid plexus neoplasms (CPNs). The normal choroid plexus cells reacted with Ricinus communis (RCA-I). Canavalia ensiformis (Con A), Limax flavus (LFA) and Triticum vulgaris (WGA), while Arachis hypoaea (PNA) stained them only after the removal of sialic acid. Human fetal choroid plexus cells at 8 weeks gestation already showed the same lectin-binding patterns as adult ones. All CPNs were stained by RCA-I and Con A in a similar manner as the normal choroid plexus cells. Although seven CPNs were positive for LFA, two CPCs were not stained by LFA, which bound to sialic acid. Two LFA-positive CPPs were stained by PNA before the removal of sialic acid. Moreover, unlike the normal choroid plexus cells, Ulex europaeus-, Glycine maximus- and Dolichos biflorus-binding sites often appeared, and WGA-binding sites of three CPNs remained even after sialic acid removal. In conclusion, the glycosialylation in normal choroid plexus cells was completed during the early embryonic stage. The lectin-binding patterns of CPNs were heterogenous in each case. The alternation of the glycosialylation and/or acquisition of binding sites for some lectins was sometimes observed through a neoplastic transformation. PMID- 1927270 TI - Peripheral and central distal axonopathy of suspected inherited origin in Birman cats. AB - Three female cats, littermates born from clinically normal parents, were examined at 8 to 10 weeks of age because of a slowly progressive posterior ataxia. Another cat from a previous litter from the same parents suffered from similar neurological symptoms. Histopathological examination of the nervous tissues of these animals revealed degeneration of axons and myelinopathy in a distal distribution pattern. Both peripheral nerves and central nervous system were involved. The central nervous system lesions were most prominent in the lateral pyramidal tracts of the spinal cord, the fasciculi gracili of the dorsal column in the cervical spinal cord and the cerebellar vermian white matter. In the PNS numerous degenerating nerve fibers were found in the sciatic nerves but not in the spinal nerve roots. Our findings show that these cats were suffering from a hereditary multisystem degeneration with a distribution pattern of the lesions suggestive of a distal axonopathy. PMID- 1927269 TI - Prevention of diisopropylphosphorofluoridate-induced myopathy by botulinum toxin type A blockage of quantal release of acetylcholine. AB - Botulinum toxin type A (BTx), which blocks quantal and partially reduces spontaneous nonquantal acetylcholine (ACh) release at neuromuscular junctions, was tested for its possible attenuating effect on diisopropylphosphorofluoridate (DFP)-induced muscle lesions. The extent of muscle lesion in extensor digitorum longus and soleus muscle of DFP injected rats with and without BTx pretreatment was evaluated using light and electron microscopic procedures. In parallel experiments, acetylcholinesterase (AChE) activity was measured and the functional state of muscles in experimental groups was determined by electrophysiological methods. The results show that pretreatment with BTx almost completely protects the muscles from DFP-induced spontaneous activity and lesions in spite of critically inhibited synaptic AChE. These results are consistent with the conclusion that the effect is not mediated by direct action of organophosphate on muscle, but by the accumulation of ACh resulting in muscle hyperactivity. Therefore, it is concluded that in conditions of acutely inhibited synaptic AChE, the quantal release of ACh is essential for lesion induction, whereas the spontaneous nonquantal ACh release, which is only partially affected in BTx blocked nerve endings, seems not to be involved. PMID- 1927271 TI - Idiopathic prolactin cell hyperplasia of the pituitary mimicking prolactin cell adenoma: a morphological study including immunocytochemistry, electron microscopy, and in situ hybridization. AB - Prolactin cell adenoma is the most frequently found lesion in surgically removed pituitaries of patients with hyperprolactinemia. However, in several instances, instead of prolactin cell adenoma, other lesions are encountered by morphological investigation. We report here the morphological findings in a patient with hyperprolactinemia who underwent transsphenoidal pituitary surgery for suspected prolactin cell adenoma. A morphological diagnosis of tumor could not be confirmed and massive diffuse prolactin cell hyperplasia was identified. The aim of this publication is to describe the lesion by histology, immunocytochemistry, electron microscopy, and in situ hybridization and to call attention to primary prolactin cell hyperplasia which can mimic prolactin cell adenoma. PMID- 1927272 TI - Repair and reconstruction of the cortical plate following closed cryogenic injury to the neonatal rat cerebrum. AB - A cryogenic lesion was induced in the parietal cortex of neonatal rats at postnatal day 2, and the chronological sequence of cellular events during repair and reconstruction of the cortical plate examined. Serial sections of cerebra obtained at varying intervals ranging from 1 to 60 days postinjury were studied by light and electron microscopy and by immunocytochemistry for fibronectin, laminin, type IV collagen, vimentin and glial fibrillary acidic protein. In addition, localization of heavily labeled neurons (generated on embryonic day 20) in the cerebral cortical plate was examined by [3H]thymidine radioautography. Repair of a well-defined coagulative lesion was accomplished with little or no mesenchymal cell proliferation in either the necrotic zone or the leptomeninges. Eventually, fusion of the adjacent cortical plates took place with the formation of a microsulcus. Migration of neurons continued to take place along the outer margins of the lesion, and postmigratory neurons accumulated within the upper cortical layers. Around the microsulcus, heavily labeled neurons aligned themselves with layers II-III of the adjacent normal cortical plate. Irregular clusters of neurons closely abutting the leptomeningeal surface were frequently noted when repair took place without an intervening molecular layer and/or a well defined pial-glial barrier. Supplementing intrinsic information inherent in migrating neurons, local environmental signals provided by the radial glia, glia limitans, basal lamina and pial-glial barrier appear to influence the polarity and final positioning of postmigratory neurons within the cortical plate. The necrotic zone within the deeper layers of the cortex eventually healed with a cell-sparse gliotic layer. The end result was a histological pattern that, in many respects, resembled that of human micropolygyria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927273 TI - Temporal profile of serum albumin extravasation following cerebral ischemia in a newly established reproducible gerbil model for vasogenic brain edema: a combined immunohistochemical and dye tracer analysis. AB - We investigated the temporal profile of the extravasation of serum albumin in a reproducible gerbil model of unilateral cerebral ischemia, using immunohistochemical and dye-tracer techniques to evaluate albumin accumulation and the occurrence of active extravasation, respectively. After 30 min of cerebral ischemia and subsequent reperfusion, immunostaining for albumin became visible in the lateral part of the thalamus during the first 3 h, and then expanded to other brain regions up to 24 h. At both 24 h and 3 days after reperfusion, massive extravasation of albumin was noted in the whole ischemic hemisphere, and this had decreased again by 7 days after reperfusion. The extent and the degree of albumin immunopositivity were almost the same in all animals examined at each period after reperfusion. The extravasation of Evans blue, which was allowed to circulate for 30 min before death, was limited to the lateral part of the thalamus during the first 6 h of reperfusion. In the circumscribed area of massive albumin extravasation, many neurons were immunopositive for albumin; most of these neurons appeared to be intact and also showed immunostaining for microtubule-associated protein 2. The current investigation clearly demonstrated that (1) albumin extravasation was produced with reliable reproducibility in this model, (2) the lateral part of the thalamus was the region most vulnerable to ischemic blood-brain barrier damage, and (3) many apparently intact neurons in the ischemic region were positive for albumin. PMID- 1927274 TI - Migration of xenogenic astrocytes in myelinated tracts: a novel probe for immune responses in white matter. AB - Experimental brain transplantation allows the study of the development of the immune response against brain antigens within the brain itself. This laboratory has developed a transplantation model in which rabbit embryo brain fragments are placed in the brains of newborn mice. The migration of xenogenic astrocytes is traced by a monoclonal antibody which combines with donor but not host glial fibrillary acidic protein. In the first 4 weeks after transplantation, the donor astrocytes successfully migrate, often within myelinated tracts. Following this period, T cells make their appearance and xenogenic astrocytes disappear by 10 weeks. The propensity for clearly identified foreign astrocytes to migrate in myelinated tracts coupled with a well-defined time course of host-vs-graft interaction suggested that the model could be used to study the immune response in white matter. The studies reported here provide sequential examples of the relationship between migration by foreign astrocytes in myelinated tracts and the development of the host immune response. Extensive migration in white matter tracts was first observed in the absence of any T cell response. Subsequently T cells were found at the transplantation site. Finally Ia was found to be expressed on blood vessels and microglia were strongly reactive in white matter that contained T cells but no foreign astrocytes. These observations support the suggestion that the model can be used to more precisely define cellular immune events that occur within white matter. PMID- 1927275 TI - Gold-labelled dystrophin molecule in muscle plasmalemma of mdx control mice as seen by electron microscopy of deep etching replica. AB - The Duchenne muscular dystrophy product 'dystrophin' has been shown to be located at the inner surface of normal muscle plasma membrane. This study was undertaken to visualize the shape of dystrophin molecules and their topographical distribution at the inner surface of murine skeletal muscle plasma membrane. The immunogold electron microscopy of plastic-embedded quadriceps femoris muscles of six mdx mice and six control mice showed the presence of gold particles along the muscle plasma membrane undercoat of all muscle samples from the control mice without any antibody reaction in the mdx mice muscles. The gold-labelled muscles of six mdx and six control mice were quickly frozen by liquid helium in a rapid freeze apparatus. High magnification electron microscopy of the quick-freeze, deep-etch, rotary-shadow replicas of the gold-labelled muscles demonstrated the presence of dystrophin molecules associated with gold particles at the cytoplasmic surface of mdx control mice. The dystrophin molecules displayed a variety of shapes, such as rods with a reduction in diameter from one end to the other end and/or with the enlargement of their end(s). These dystrophin molecules were incorporated in the meshwork of muscle plasma membrane-associated cytoskeletons. PMID- 1927276 TI - Schwann cell migration through freeze-killed peripheral nerve grafts without accompanying axons. AB - Freeze-dried tibial nerve grafts were anastomosed to either the proximal stump or the distal stump of severed tibial nerves in adult inbred Fischer rats. In the case of grafts attached to the proximal stump the tibial nerve was ligated three times, the most distal ligature from the spinal cord being 1 cm from the site of anastomosis. In both types of experiment Schwann cells were, therefore, free to enter the initially acellular grafts without accompanying axons. The grafts were examined 17 days to 12 weeks after operation. Immunofluorescence for S-100 protein was used to evaluate the distance migrated by the Schwann cells and electron microscopy was used to examine the morphology of the cells which invaded the grafts. Schwann cell migration was similar from the proximal and distal stumps. The migrating Schwann cells formed columns which resembled bands of Bungner. They were found mainly, but not exclusively, inside the pre-existing basal lamina tubes left behind by the killed nerve fibres. Some Schwann cells secreted a thin, patchy basal lamina even though they lacked axonal contact. Schwann cell columns became partially compartmentalized by fibroblast processes. Myelin and other debris were removed most rapidly in those parts of the grafts penetrated by large numbers of Schwann cells. The maximum distance the Schwann cells penetrated into the grafts was 8.5 mm and this was achieved by 6 to 8 weeks after operation. This is about half the maximum distance migrated by Schwann cells accompanying regenerating axons through similar grafts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927277 TI - Distribution pattern and functional state of alpha 1-antichymotrypsin in plaques and vascular amyloid in Alzheimer's disease. A immunohistochemical study with monoclonal antibodies against native and inactivated alpha 1-antichymotrypsin. AB - Monoclonal antibodies (mAbs) were raised against inactivated alpha 1 antichymotrypsin (ACT) to study the presence and functional state of the serine protease inhibitor alpha 1-antichymotrypsin in cerebral amyloid deposits in Alzheimer's disease. A panel of seven different mAbs was obtained; six of them were directed against neoepitopes that are expressed on ACT after interaction with proteases (inactivated ACT) and one mAb was directed against an epitope that is exposed both on native and inactivated ACT. The mAbs against neoepitopes could discriminate native ACT from complexed and inactivated ACT in vitro as shown in binding experiments in the presence of either native or inactivated ACT. With the mAbs against ACT we found that: (a) besides classical congophilic plaques, amorphous noncongophilic beta/A4-positive plaques were stained; (b) amorphous and classical plaques reacted with both types of mAbs against ACT indicating that this ACT was either complexed to a protease or proteolytically inactivated; (c) vascular amyloid was not stained for ACT. The presence of ACT in amorphous and classical plaques and its absence in vascular amyloid may indicate differences in the proteolytic degradation of preamyloid into amyloid fibrils. Our study strongly suggests that ACT is biologically active in amyloid plaques from an early stage. PMID- 1927278 TI - The cerebral cortex in congenital hydrocephalus in the H-Tx rat: a quantitative light microscopy study. AB - Hydrocephalus in the H-Tx rat first develops in late gestation and causes death at 4-7 weeks. The effect of hydrocephalus on overall cortical dimensions and on five specific regions (frontal, sensory-motor, parietal, auditory and visual) has been studied by quantitative light microscopy at 10 and 30 days after birth. The lateral ventricle volumes in hydrocephalic rats were about 40 x larger than controls and increased fourfold between 10 and 30 days. Cortical volume was reduced by a small amount at 10 days but was larger in hydrocephalics at 30 days. Thinning of the cortical mantle was severe with disruption of the laminar structure, particularly in the auditory and visual regions, where it was already present at 10 days. The density of cortical cells (neurones and glia) was not altered in hydrocephalics at 10 days but was reduced in all regions at 30 days. Estimates of total cell number suggest that the lower density was not associated with an overall loss of cells. Capillary numerical density was not affected by the hydrocephalus at 10 days after birth but by 30 days it was significantly lower, particularly in the worst-affected posterior regions. The results show that the cerebral cortex is severely distorted and that in advanced hydrocephalus, although overall cell number is not affected, both cell density and capillary density are lower by up to 30%. PMID- 1927279 TI - Neuronal autophagy in experimental scrapie. AB - In this study we report the formation of giant autophagic vacuoles (AV) in neurons in experimental scrapie in hamsters. Autophagy is an important step in the cellular turnover of proteins and organelles. It is known to occur in neurons under physiological as under pathological conditions. Giant AV, however, are seen very rarely only in pathological states. In our model AV are much more numerous after intracerebral (i.c.) transmission of the scrapie agent than after the transmission via the intraperitoneal route which points to a correlation between the intensity of the process and the period of incubation. As the appearance of the AV in our model is correlated chronologically with that of scrapie-associated fibrils, at least after i.c. transmission, the process may be related to a disturbance of cellular protein metabolism and, thus, to the processing of prion protein. PMID- 1927280 TI - Prominent cortical atrophy with neuronal loss as correlate of human immunodeficiency virus encephalopathy. AB - A 25-year-old homosexual AIDS patient presented with progressive cognitive, motor and behavioral disturbances consistent with HIV encephalopathy. CT scans demonstrated progressive diffuse brain atrophy. Neuropathology showed predominant cortical changes including severe neuronal loss corroborated by morphometry. Only minimal changes were found in the white matter and basal ganglia. Immunocytochemistry for HIV stained occasional microglial cells more markedly in the cerebral cortex. This suggests that HIV infection of the brain may cause predominant cortical nerve cell loss, and that HIV encephalopathy is not necessarily due to white matter lesions. PMID- 1927281 TI - Cerebro-ocular dysplasia--muscular dystrophy (Walker Warburg) syndrome. Findings in 20-week-old fetus. AB - A 20-week fetus affected with cerebro-ocular dysplasia and muscular dystrophy (Walker-Warburg Syndrome) is reported. The central nervous system (CNS) findings were typical of those previously described in this disorder, and were characterized by lissencephaly, hydrocephalus, and cerebral and cerebellar cortical dysplasia with glial and neuronal displacement into the leptomeninges. In addition, severe hypoplasia of pyramidal tracts were noted in the brain stem and spinal cord, as well as malformation of the inferior olivary and dentate nuclei. Skeletal muscle and eyes appeared normal on light microscopy. The genetic defect in this disorder is expressed in the CNS early during the first trimester and causes a marked disorder of cellular migration. Overt changes in muscle occur during a later period. The changes in the CNS are similar to, but more severe than, those found in Fukuyama congenital muscular dystrophy, and both may represent a failure of constraint of neuronal migration. Whether the syndromes characterized by cerebro-ocular dysplasia and muscular dystrophy are genetically heterogeneous or allelic variations is unknown. Molecular genetic analysis should elucidate this question. PMID- 1927282 TI - Radiographic signs in the temporomandibular and hand joints in patients with psoriatic arthritis. AB - The temporomandibular (TMJ) and hand joints of 64 patients with psoriatic arthritis (PA) were examined radiographically with panoramic tomography and dorsovolar projection. The associations between radiographic signs in the condyle of the TMJ and finger joints were analyzed with Pearson's product-moment correlation coefficient. Twenty-six patients (41%) had radiographic signs in their TMJs. Arthritic signs were seen in 14 (22%) and degenerative signs in 12 (19%) patients. Fifty-five patients (86%) had radiographic signs in their hands; 33 patients (52%) had arthritic and 22 (34%) degenerative signs. In the TMJ statistically significant correlations were found among erosion, flattening, and cortical sclerosis and also between osteophyte and cortical sclerosis. In the finger joints erosion correlated significantly with dislocation and loss of space. Erosion in the condyle of the TMJ was the only sign that correlated with changes in the finger joints such as erosion, dislocation, and ankylosis. Erosion in the TMJ also correlated with erosion in the metacarpophalangeal joint and wrist. PMID- 1927283 TI - Fluorosis of deciduous teeth and first permanent molars in a rural Kenyan community. AB - The severity and distribution of fluorosis in the deciduous dentition of 76 children in a low-income community near Nairobi were studied. Seventeen children comprised a low-F (fluoride) group (water less than 0.7 ppm F) and 59 a high-F group (water approximately 9 ppm F). The high-F group had scores greater than or equal to 5 in the Thylstrup & Fejerskov classification system for 29% of the deciduous tooth surfaces, compared with 7% in the low-F group. Comparison between the scores of the second deciduous and the first permanent molars showed no significant difference in the high-F group (p greater than 0.001), whereas the deciduous molar was significantly less severely affected in the low-F group (p less than 0.001). The deciduous molars of the two groups differed significantly (p less than 0.002), but not the permanent molars (p greater than 0.10). Early introduction of tea might have been a major contributor to the distributions of fluorosis, particularly in the low-F group. PMID- 1927285 TI - Chronic use of opioids in intractable facial pain. A case report. AB - The use of opioids in chronic non-malignant pain conditions is largely rejected by the health authorities. Their concern is mostly due to the potential problems of addiction and other adverse effects of opioids. However, in certain pain conditions opioids may be the only effective remedy. This article presents some guidelines for the use of narcotics for non-cancer pain. A case is presented in which methadone in small doses in combination with an antidepressant was the first drug capable of alleviating the patient's suffering. The drug was effective during a period of 9 months. PMID- 1927284 TI - Cervical vertebral dimensions in 8-, 11-, and 15-year-old children. AB - In a sample of 107 boys and girls registered at 8, 11, and 15 years of age and 22 adults the statural height and the height and length of the cervical vertebrae, measured from lateral skull radiographs, were studied. The height and length of the vertebrae increased with age among the children and were non-significantly higher for the girls in each age group. The 15-year-old girls matured earlier, reaching adult values at this age. The 15-year-old boys still showed significantly smaller values for vertebral height and length compared with the adult men. Statural height was significantly correlated with the variables for vertebral growth at 8 and 11 years, whereas there was no correlation at 15 years of age among the children who had passed the pubertal peak height. The development of the vertebrae showed similarities with earlier reported skeletal maturity indicators found in the hand-wrist area and could as such offer an alternative method of assessing maturity without the need for hand roentgenograms. PMID- 1927287 TI - Intramuscular and skin surface temperatures of the resting human superficial masseter muscle. AB - The intramuscular and skin surface temperature of the central part of the superficial masseter muscle was measured with thermocouples in 25 individuals with none or mild signs of craniomandibular disorders. The intramuscular temperature averaged 35.7 degrees C, varying between 34.6 and 36.5 degrees C. The average difference between the right and left sides was 0.4 degrees C. The skin surface temperature averaged 33.2 degrees C, varying between 31.1 and 35.4 degrees C. The average difference between sides for this temperature was also 0.4 degrees C. The correlation between intramuscular and skin surface temperature was weak, and the average difference was 2.5 degrees C, with a range from 0.4 to 4.6 degrees C. The spatial variation in skin surface temperature 5 mm around the central measuring point was small. The reproducibility of both intramuscular and skin surface measurements, as assessed by the standard deviation for a single measurement, was acceptable. PMID- 1927286 TI - Evaluation of an infrared light absorption method for objective assessment of oral mucosal dryness. AB - The aim of this study was to evaluate an infrared light absorption (ILA) method for registration of dryness of the oral mucosa. Measurements were performed in the buccal and in the lip mucosa immediately before and every 30 min after submucosal injection of 1.0 ml methylscopolamine nitrate in nine healthy subjects. For comparison, a dental mirror sliding friction test was used. About 1.5 h after injection the ILA method showed statistically significant (P less than 0.01) decreases of values in both the buccal and the lip mucosa. However, in the individual subjects the deviations from initial values showed only slight agreement when measured with the ILA method and the mirror friction test. Thus, the ILA method does not seem to be suitable for registration of individual variations in oral mucosal dryness. PMID- 1927288 TI - Edema-preventing mechanisms in rat gingiva. AB - The long-term effect of increased local venous pressure (Pv) on interstitial fluid pressure (Pi), colloid osmotic pressure (COPi), and fractional removal rate of 125I-labeled human serum albumin (kAlb) was studied in rat gingiva. Measurements were performed on experimental animals and sham-operated controls up to 4 days after ligation of jugular veins. On the day of ligation Pv in the facial veins rose from 2.5 +/- 0.3 (SD) to 15.8 +/- 2.8 mm Hg and stayed at about this level for 2 days before a decrease to 7.4 +/- 0.9 mm Hg on day 4. In free gingiva Pi rose from an average of 3.5 +/- 0.4 to a maximum of 6.3 +/- 0.7 mm Hg, whereas in attached gingiva the corresponding increase in Pi was from 6.0 +/- 0.7 to 11.1 +/- 2.1 mm Hg. One day after the ligation COPi in wick fluid from gingiva was reduced from the control level of 10.6 +/- 1.4 to 4.5 +/- 0.9 mm Hg. COP in plasma and COPi in subcutaneous tissue on the back were unaffected. The removal rate of 125I-labeled albumin (kAlb) from the gingiva showed a nearly threefold increase after venous ligation, from 0.073 +/- 0.01 to 0.211 +/- 0.06 h-1. It is concluded that in free and attached gingiva, both a rise in Pi and a decrease in COPi will counteract the increased filtration pressure and thus prevent edema formation during venous stasis. The fall in COPi is most likely due to increased lymph flow and not dilution, as venous stasis significantly increased kAlb without any visible increase in gingival volume. PMID- 1927289 TI - Five-year longitudinal recordings of functional variables of the masticatory system in adolescents with intact and restored dentitions. A comparative anamnestic and clinical study. AB - Recordings of functional variables of the masticatory system were made in 184 subjects, 18-20 years old, 5 years after the first examination. One hundred and six subjects had restored dentitions at both examinations (group F), 35 subjects with previously intact dentitions had received fillings during the follow-up period (group FI), and 43 subjects had intact dentitions at both examinations (group I). In conformity with the first examination 5 years earlier, the subjects in group F had higher scores for dentin facets on the first lower molar. Together with the finding of more frequent attrition on the distal part of the occlusal surface of the second lower molar, this finding indicates more functional or parafunctional activity in restored dentitions. Unilateral contacts in the retruded contact position (RCP) were equally common in all three groups, but the contacts in RCP were more often located in the molar region in group F. The finding at the first examination that interference causing a lateral slide of the mandible between RCP and the intercuspal position (ICP) was commoner in restored dentitions was not confirmed in the present study. Nor did the correlation analysis show any relationship between occlusal factors and signs and symptoms of mandibular dysfunction. However, the differences found between subjects with intact and restored dentitions indicate that the iatrogenic effect of dental filling therapy merits more consideration and more extensive research. PMID- 1927290 TI - Marginal leakage in occlusally loaded, etched, class-II composite resin restorations. AB - Microleakage was studied in class-II cavities restored with a calcium hydroxide liner and an adhesive system combined with two different posterior composite resins. The restorations were exposed to repeated loading when immersed in dye solution. The teeth were cut, and microleakage along the cavity walls and into dentin was evaluated by light microscopy. Dye penetration at the interface between the cavity and the restoration was recorded in 61% of the loaded and in 30% of the unloaded teeth. The difference between loaded and unloaded was greater for the teeth lined with Life than with Gluma dentin bonding. PMID- 1927291 TI - On the art of referring to previously published material. PMID- 1927292 TI - Acta sixty years ago. Vaginal cesarean section in cases of placenta previa. PMID- 1927293 TI - Pregnancy complicated by acute appendicitis. PMID- 1927294 TI - Catechol-O-methyltransferase activity in red blood cells in threatened preterm labor; effect of indomethacin and nylidrin. AB - Catecholamines that are released in excess during human labor are inactivated mainly by catechol-O-methyltransferase (COMT). To ascertain whether uterine contractions are associated with changes in COMT activity in red blood cells (RBCs), we studied 25 women with established threat of preterm labor between 25 and 33 weeks of gestation, 25 gestational age-matched control women not experiencing uterine contractions, 25 women who were in term labor, and 25 non pregnant healthy women. COMT activity in pregnant women without uterine contractions (median 0.3, range 0.1-0.8 pmol/mg/min) was lower (p less than 0.05) than that in non-pregnant control series (median 0.5, range 0.3-0.7 pmol/mg/min). RBCs' COMT activity in women with preterm labor (median 0.6, range 0.2-1.1 pmol/mg/min) was greater (p less than 0.05) than that in pregnant and non pregnant control women, but similar to that during term labor (median 0.5, range 0.2-1.7 pmol/mg/min). Women with preterm labor were treated with indomethacin (12 women) or nylidrin (13 women). Nylidrin treatment was accompanied by a 35% rise in COMT activity 3 h later, whereas indomethacin caused no significant change. Apart from cessation of uterine contractions during tocolysis, 13 women went into labor before the 37th gestational week, but their pretreatment COMT activity (median 0.7, range 0.2-1.1 pmol/mg/min) did not differ from COMT activity in women whose pregnancy proceeded to term (median 0.5, range 0.3-1.0 pmol/mg/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927295 TI - Hemodynamic measurements with Swan-Ganz catheter in women with severe proteinuric gestational hypertension (pre-eclampsia). AB - Ten women with severe pre-eclampsia, i.e. a blood pressure greater than or equal to 150/110 mmHg or 140/90 mmHg and proteinuria greater than 3 g/24 h were, after initial antihypertensive treatment, centrally monitored with a pulmonary artery catheter (Swan-Ganz). All had been normotensive in early pregnancy. Mean age was 29 years (range 23-37). Mean gestational age upon admission was 29 weeks (range 23-36) and 7 of the women were nulliparous. Nine of the 10 patients had subjective symptoms, e.g. headache and/or epigastric pain. All were considered in need of intensive care. Two patients were found to have an abnormal coagulation and liver function. All patients had normal serum creatinine values despite proteinuria. Hypertension was treated with dihydralazine and/or labetalol. Volume substitution was carried out with plasma and albumin. The women could be divided into two groups: 5 patients where progress of the disease despite therapy led to delivery within 24 h, and 5 patients whose diastolic blood pressure could be stabilized around 100 mmHg after treatment and pregnancy could be prolonged by 5 13 days. Common for all patients was a hyperkinetic circulation with an increased cardiac output despite a variety of central pressures. Invasive monitoring of central pressures with a Swan-Ganz catheter demonstrated that the clinical status could be stabilized and the pregnancy prolonged in 5 of the 10 women with severe pre-eclampsia. The variety of the central hemodynamic values illustrates clearly that treatment has to be individualized regarding antihypertensive medication, fluids and diuretics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927296 TI - The use of antiprogestin (RU 486) for termination of second trimester pregnancy. AB - Pretreatment with laminaria tent is often used in prostaglandin-induced second trimester abortion to increase efficacy and shorten induction-to-abortion time. In the present study, two alternatives to soften the cervix and dilate the cervical canal, the antiprogestin RU 486 and intra-cervical application of PGE2, were studied. The study included 71 women requesting legal abortion in the 15th to 23rd week of pregnancy who were treated with repeated vaginal applications of 9-methylene PGE2 in a hydrophilic gel (5 mg every 4th hour) following pretreatment with 200 mg of RU 486 and/or intracervical administration of 0.5 mg of PGE2 gel. The mean interval from start of vaginal prostaglandin treatment to abortion was 13.2 h after intracervical PG-treatment, 10.0 h after antiprogestin and 6.6 h after the combined pretreatment. Patients who received pretreatment with RU 486 alone or in combination with intracervical PGE2 experienced the lowest frequency of episodes of vomiting. Of these two pretreatment alternatives, RU 486 alone has the advantage of a shorter hospital stay. It can be concluded that vaginal administration of 9-methylene PGE2 after pretreatment with RU 486 was a highly effective, safe and rapid procedure for termination of mid-trimester pregnancy, was well tolerated by the patients and was associated with few side effects. PMID- 1927297 TI - Unsupplemented breastfeeding in the maternity ward. Positive long-term effects. AB - Feeding routines in the maternity ward were investigated in 204 mother-infant pairs before and in 203 after a change towards earlier, more frequent breastfeeding and elimination of routine substitute feeds. In the intervention group, the volume of breast-milk increased, while the use of formula and sugar solution decreased correspondingly. The infants in the intervention group lost more weight during the first 2-3 days (6.4% versus 4.6%), but regained their birth weight faster than the supplemented control group. The incidence of hyperbilirubinemia was not significantly different in the two groups. No cases of hypoglycemia were diagnosed. At 6 months, 87% of the infants in the intervention group were still fed at the breast, compared with 66% in the control group. The weight curves were comparable up to 9 months, when intervention group infants were found to weigh slightly less. These follow-up results must be interpreted with some caution due to the low but comparable response rate of the two groups. Thus the intervention study demonstrated that healthy, full-term infants usually have no need for supplements to their mothers' milk provided they have had a satisfactory start in life with early and frequent feeds at the breast. The follow-up study indicated that a more "physiological" start of breastfeeding may have had a positive long term effect on the overall duration of the lactational period. PMID- 1927298 TI - Neither exogenous nor endogenous GnRH stimulation alters the bio/immuno ratio of serum LH in healthy women and in polycystic ovarian disease. AB - The purpose of this study was to re-evaluate the quantitative and qualitative responses of LH to exogenous and endogenous GnRH stimulation in normally cycling women and in polycystic ovarian disease (PCOD). Responses of serum LH to GnRH (100 micrograms i.v.) and the opioid antagonist naloxone (10 mg i.v.) were determined in healthy women in the early (n = 5) and late (n = 4) follicular phase, and in patients with PCOD (n = 20). Serum bioactive (B) LH was determined by a mouse interstitial cell in vitro bioassay, and immunoreactive LH by a conventional RIA (I-LH) and a novel sensitive (0.05 IU/l) and specific immunofluorimetric assay (F-LH). The B/I (2.4 +/- 0.1) and B/F (2.7 +/- 0.6) ratios in basal serum samples of the PCOD patients were significantly higher (p less than 0.05) than the corresponding ratios (1.6-1.8 and 1.8-2.0) of the control women. GnRH stimulated the secretion of I-LH (2-4-fold), F-LH and B-LH (3 5-fold each) in all groups studied. There were no apparent changes of the B/I and B/F ratios in normal women during early follicular phase or in patients with PCOD. However, the normal women during late follicular phase displayed a significant (p less than 0.05) increase in the B/I ratio, albeit no change was found in the B/F ratio. During naloxone-induced endogenous GnRH responses, the control women during late follicular phase showed a 3-6-fold increase in B-LH, I LH and F-LH, with unchanged B/I and B/F ratios.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927299 TI - Sexual behavior and sexually transmitted diseases among Swedish university students. AB - Students at Uppsala University, Sweden, were interviewed about their sexual behavior, their knowledge of and attitudes to sexually transmitted diseases (STDs) and related issues. The purpose of the study was to ascertain trends in behavior and attitudes as an indication of the likely risk of the spread of STDs, in particular AIDS, among students. Results revealed that change of partner was commonplace. A significant number of students had suffered from an STD. Students' claims that their own sexual practices, and those of others, had changed as a result of the AIDS epidemic, proved to be unsubstantiated in their behavior. Although contraceptive use was high, condom use with change of partner was infrequent. Alcohol played a significant role in impairing judgement. Despite a reasonably sound knowledge of STDs, the students exhibited a high degree of risk taking behavior. The study has highlighted the dichotomy between knowledge and practice in student sexual behavior. Notable was the lack of perception among university students of their own risk of contracting STDs. PMID- 1927300 TI - Urodynamic assessment and lateral urethrocystography. A comparison of two diagnostic procedures for female urinary incontinence. AB - We compared urodynamic findings and results of lateral urethrocystography in 84 case. The aim of the study was to establish a possible correlation between anatomic findings and functional results. Clinically, a significantly greater increase in the normal axis of urethral inclination was noted in patients with a urodynamic diagnosis of stress incontinence than in patients with urge incontinence or for normal urodynamic findings. Lateral urethrocystography vis-a vis urodynamic assessment proved to be a method having high sensitivity (91%) but low specificity. These two methods supply different but complementary data. Together with the patients' medical history, the assessment of their complaints, clinical vaginal examination, and clinical stress test, they offer valuable information for an efficient therapeutic concept. PMID- 1927301 TI - Laser and cryo surgery for cervical intraepithelial neoplasia. A randomized trial with longterm follow-up. AB - In a randomized study, 204 patients with exocervical intra-epithelial neoplasia were allocated to either laser evaporation (103) or cryocoagulation (101). The patients were treated on an outpatient basis without anesthesia. In the case of initial treatment failure the same method was to be used for retreatment. One hundred and eighty-seven patients were followed-up for an average of 50 months (12-80). Eighty-six of 94 laser-evaporated patients (91%) and 89 of 93 cryocoagulated patients (96%) were cured after one treatment. Five of 8 laser failures and 3 of 4 cryo failures were cured by retreatment. The cure rate after one or two laser evaporations was 97% (91 of 94 patients), and after one or two cryo coagulations, 99% (92 of 93 patients). Eighty per cent of residual or recurrent neoplasia occurred within 15 months and 96% within 2 years of treatment. No invasive neoplasia occurred during the follow-up period and no tendency was seen towards higher grades of intra-epithelial neoplasia in the failures compared with the initial diagnoses. It is concluded that laser evaporation and cryocoagulation are equally effective for the treatment of exocervical intra-epithelial neoplasia. PMID- 1927302 TI - Prenatal diagnosis of craniopagus. AB - The long-term prognosis of craniopagus, a congenital abnormality of monozygotic twinning, is strictly correlated to the type of shared cerebral structures. Hence, the purpose of prenatal diagnosis is not only to detect this malformation, but also to identify the fused cerebral structures. The authors report a prenatal diagnosis of a craniopagus during the second trimester of pregnancy. Comparison of ultrasound data with the pathological findings underlines that ultrasound is of great value in detecting malformations, but it is not alone sufficient to identify the types of conjoined cerebral structures. PMID- 1927303 TI - Malignant schwannoma in pregnancy. AB - We report a case of malignant schwannoma on the distal forearm in a pregnant woman with neurofibromatosis. The problems of managing concomitant pregnancy and this particular maternal malignancy are discussed, leading toward a favorable maternal-fetal outcome. PMID- 1927304 TI - Metastasis in skeletal muscle secondary to squamous-cell carcinoma of the uterine cervix. AB - Skeletal muscle metastases are rare, but occur most often with lymphomas, as well as being occasionally described secondary to breast, lung, prostatic, colonic, pancreatic and renal cell carcinomas--but not uterine cancers. A case of skeletal muscle metastasis is presented, originating from a primary squamous-cell carcinoma of the uterine cervix. PMID- 1927305 TI - Treatment of unruptured tubal pregnancy by an hysteroscopic procedure. AB - Two cases of tubal pregnancy are presented. Both were treated successfully with hysteroscopic tubal instillation of prostaglandin F2 alpha. PMID- 1927306 TI - Re.: Nielsen GL, Nielsen PH. Results of oral glucose tolerance test performed following birth of a baby with birthweight above 4500 gr. PMID- 1927307 TI - The middle-Norway eye-screening study. II. Prevalence of simple and capsular glaucoma. AB - In this population-based screening study, dealing with 1941 persons above 64 years of age from three different municipalities, the overall open-angle glaucoma prevalence was found to be 8.3%. The prevalence in the separate areas (7.0%, 8.6%, and 9.5%) were not statistically different. Roughly 30% of the population with pseudo-exfoliation syndrome had glaucoma, and 4.2% had ocular hypertension, whereas the corresponding figures for those without pseudo-exfoliation were 4% and 0.8%, respectively. The high glaucoma rates are partly due to the high pseudo exfoliation prevalence in the area. The prevalence of the capsular glaucoma increased towards a maximum between 75 and 79 years of age, whereafter the curve declined. This may indicate reduced survival time of glaucomatous patients. PMID- 1927308 TI - Gonioscopic findings in Greek patients with exfoliation glaucoma. AB - A prospective gonioscopic evaluation was carried out upon a cohort of Greek patients who had undergone trabeculectomy for open-angle glaucoma. Sixty-five patients were found to show clinical evidence of exfoliation glaucoma (EXG), whilst nine patients were deemed to have primary open angle glaucoma (POAG). The gonioscopic features of these eyes and of 43 non-operated eyes from the same patients with either exfoliation syndrome (EXS) or EXG are presented. The median degree of angle pigmentation was significantly higher in the operated eyes with EXG when compared with the POAG cases. In the operated eyes, deposition of exfoliation was found on the ciliary processes in 82% of cases and on the zonules in 52%. PMID- 1927309 TI - Glaucoma case detection. AB - In Dalby more than 1,000 residents have been followed for a decade (1977-1987) with periodic comprehensive eye examinations including family history, ophthalmoscopy, slit-lamp examination, applanation tonometry, and computerized perimetry. The large majority were followed at long intervals (2.75 and 5.65 years). Ophthalmoscopy and tonometry were used to select a minor part of the population to be followed at shorter intervals. In this way 16 out of 24 manifest glaucomas detected after the first survey were found among patients followed at shorter intervals. A closer look at the data suggested that the selection could have been further improved if the slit-lamp examination and the family history had been used in much the same way as ophthalmoscopy and tonometry. On this basis new criteria to select persons said to have 'presumptive glaucoma' are proposed. PMID- 1927310 TI - Neuroretinal rim area in low tension glaucoma: effect of nifedipine and acetazolamide compared to no treatment. AB - The purpose of this study was to measure the change of neuroretinal rim area in patients with low tension glaucoma on- and off-treatment. Thirty-two patients were followed up for a mean of 2.6 years. Ten patients received treatment with nifedipine, 11 patients with acetazolamide and 11 patients had no treatment. The total change of rim area and the yearly rate of rim area change did not differ statistically significantly between the three groups. Seven patients in each group suffered from cold hands and feet. The response to cold provocation visual field testing was positive in 25% of patients. Neither the history of cold hands and feet nor the cold provocation test result affected the rate of progression of optic disc abnormalities. Nifedipine and acetazolamide treatment seemed to show no advantage over no-treatment in our patients. PMID- 1927311 TI - Long-term outcome following trabeculectomy: I Retrospective analysis of intraocular pressure regulation and cataract formation. AB - Decrease of intraocular pressure (IOP) and the occurrence of cataract were analysed in 75 patients of a community-based material followed for 6-12 years after trabeculectomy. IOP was controlled (less than or equal to 21 mmHg) with or without additional treatment in approximately 90% of the eyes, both at 5 years and at the last visit. The share of eyes requiring no medication for IOP control decreased linearly with time from approximately 90 to 60% between one and 10 years postoperatively. Thirty-eight per cent of the patients without cataract at the time of operation suffered from cataract development during follow-up. The prevalence of dense cataract producing severe visual loss at the last visit was 47%. The occurrence of cataract was correlated with the age of patients at operation. Cataract formation showed no relationship of statistical significance with preoperative treatment, with time since surgery, the magnitude of preoperative IOP and the reduction of postoperative IOP. PMID- 1927312 TI - Long-term outcome following trabeculectomy: II Visual field survival. AB - The long-term changes of the visual field defects of 54 glaucoma patients operated on with trabeculectomy were reviewed. Five years after operation 28% of the patients had suffered from further loss of visual field despite lowering of the intraocular pressure (IOP). All but three of these patients had their postoperative IOP regulated within statistically normal levels (11-21 mmHg). All patients with continued loss of postoperative field were generated from groups of patients with milder to moderate preoperative field defects (stages 0-III classification of Aulhorn, 1979). No patients suffered from sudden field loss after surgery. The mean of the preoperative IOP and the mean of the percent IOP reduction postoperatively were not significantly different in patients with or without continued postoperative visual field loss. This indicates that other factors than normalization of intraocular pressure play an important role in the group of patients with progression of visual field defects following surgery. PMID- 1927313 TI - Age-related changes in the human lens. Clinical assessment of age-related changes in the human lens. AB - We compared two methods for assessing changes in the human lens associated with age. The first is a subjective method for quantifying light absorption by the lens. It is useful for determining the functional effect of age-related increases in lens density, especially for short-wavelength light. The second method objectively and rapidly measures the increase in scattered light with increasing lens density. These two methods accurately measured age-related changes and were highly correlated with each other (r = 0.72, P less than 0.001). Both methods were evaluated in a population of normal eyes, eyes with ocular hypertension, and eyes with primary open angle glaucoma. We found ni significant differences among these groups with either method. PMID- 1927314 TI - Factors influencing the formation of posterior capsular opacities after extracapsular cataract extraction with posterior chamber lens implant. AB - This study was designed to determine whether different factors could influence the formation of posterior capsular opacities. The study group comprised 271 patients who had undergone an extracapsular cataract extraction with implantation of a posterior chamber lens either with or without laser ridge. Between 12 and 25 months after surgery, a statistically significant difference was found with a lower rate of secondary cataract in the laser ridge group, but with respect to advanced secondary cataract, i.e. eyes which needed YAG capsulotomy, no statistically significant difference was found (P-value 0.99). No association was found between age or sex of patients, different surgeons or complications during or after surgery and the risk of getting a secondary cataract. PMID- 1927315 TI - Retinal function in birdshot retinochoroidopathy. AB - The electroretinograms (ERGs) of 15 patients with birdshot retinochoroidopathy varied from super-normal to non-recordable, depending upon the severity and the stage of the disease. The abnormal ERGs were characterized by a disproportionate decrease of the b-wave amplitude compared with the a-wave amplitude, demonstrating the negative (-) type response. This distinct ERG pattern has not been observed in any other type of uveitis or chorioretinitis, and appears specific to birdshot retinochoroidopathy. ERG findings indicate that in birdshot retinochoroidopathy the neural layers of the retina are more diffusely and severely involved than the receptor-retinal pigment epithelium-choroid complex. In the most advanced stage, the patients becomes night blind with a non recordable ERG, a situation that is essentially the same as retinitis pigmentosa, except that pigmentation is conspicuously absent in the fundus. PMID- 1927316 TI - Precision in automated refraction. AB - Forty-six eyes were examined with automated refraction with the Nidek 1000-AR autorefractometer to determine how large variation there was in readings of each patient, under dry conditions (without cycloplegia) and in atropine and cyclopentolate cycloplegia. Likewise, the differences between methods of cycloplegia were analysed with regard to sphere, cylinder power, and axis. Overall the variation in each set of measurements was greatest for the spherical component, and a larger variation was found in the youngest age group. Variation in cylinder power and axis was small. Cycloplegics had a significant influence on the spherical component of automated refraction, and a mean difference of 0.76D was found between atropine and dry readings, and 0.23D between atropine and cyclopentolate readings. The differences between cycloplegic and dry readings in cylinder power and axis were insignificant. A regression model relating spherical power of dry and cyclopentolate automated refraction was developed, and the predictive power of this equation was tested. PMID- 1927317 TI - Automated refraction. A comparative study of automated refraction with the Nidek AR-1000 autorefractor and retinoscopy. AB - A prospective study was performed on 46 eyes to compare results of different methods of objective refraction, namely automated refraction with the Nidek AR 1000 autorefractometer and retinoscopy in cycloplegia. We found that automated refraction in cyclopentolate cycloplegia gave results that differed little from results of retinoscopy in atropine cycloplegia both with respect to sphere and cylinder. Axis determination was even better with automated refraction. Dry automated refraction gave inaccurate results for the spheric component presumably because of suboptimal control of accommodation in this group of young patients. We recommend automated refraction in cyclopentolate cycloplegia as an easy, rapid, accurate and convenient method for obtaining an objective refraction where accommodative disorders are suspected. PMID- 1927318 TI - Necrosis and lymphocytic infiltration in choroidal melanomas. AB - Patient survival, tumor lymphocytic infiltration and tumor necrosis were studied and evaluated in 43 enucleated eyes with the same histological diagnosis of spindle 'B' malignant melanoma of the choroid. A significant difference (P less than 0.05) was found between the survival rate of melanoma patients with no evidence of lymphocytic infiltration and/or necrosis in the tumor, compared to those with any evidence of of lymphocytic infiltration and/or tumor necrosis. PMID- 1927319 TI - Chloride concentrations in the corneal epithelium and stroma from different species. AB - Using ion chromatography, the concentration of chloride in the corneal stroma and epithelium of ox, pig and rabbit was measured to detect possible species differences. In all three species, the chloride concentration in the stroma was found to be very similar, i.e. 363 +/- 14 mmol kg-1 dry wt in ox, 364 +/- 18 mmol kg-1 dry wt in pig and 358 +/- 24 mmol kg-1 dry wt in rabbit. In contrast, a substantially higher concentration of 232 +/- 33 mmol kg-1 dry wt was found in the corneal epithelium of rabbit in comparison to the values determined in the same tissue of ox, i.e. 137 +/- 4 mmol kg-1 dry wt and of pig, i.e. 128 +/- 24 mmol kg-1 dry wt. Using the results obtained previously for the extracellular volume (Midelfart 1988), an intracellular chloride concentration of 25 +/- 2 mmol kg-1 H2O was calculated in the bovine corneal epithelium. The results obtained in this study indicate that species differences are considered as important in studies of ion transport mechanisms in the cornea. PMID- 1927320 TI - Acute optic neuritis with normal visual acuity. Comparison of symptoms and signs with psychophysiological, electrophysiological and magnetic resonance imaging data. AB - In a prospective study of hitherto 70 patients with acute optic neuritis (ON), 18 patients aged 15-49 years (12 women, 6 men) were diagnosed as having very subtle form of ON (bilateral in 4 patients), characterized by normal visual acuity. However, their symptoms were sudden functional visual disturbances, most frequently blurred vision accompanied by pain in or around the affected eye(s). In 5 patients, the ON was a manifestation of clinically definite multiple sclerosis (MS); the remaining 13 patients had monosymptomatic ON. The duration of visual symptoms ranged from 2 to 28 days (median 7 days) at the time of examination. Although 18 patients had a normal visual acuity, i.e. 6/6 c.c. (Snellen's notation) or better, extensive studies of the visual functions (using sensitive supplementary tests) revealed various abnormalities, primarily various visual field defects, abnormal contrast sensitivity, abnormal VEP and colour vision deficiencies (often of blue-yellow type). Magnetic resonance imaging (MRI) of the brain revealed demyelinating lesions in 10 of the 13 patients with monosymptomatic ON, and in all 5 patients with definite MS. The extended disease spectrum gives reason to hypothesixe that ON may occur more frequently than previously reported, and that the described subtle form of ON could be an unnotified precocious manifestation of the demyelinating disease. PMID- 1927321 TI - Effect of test field size on the results of automated perimetry in normal subjects and patients with optic neuritis. AB - The mean sensitivities of the same 8 central test points were compared in two different programs of an automated Octopus perimeter in normal subjects and in patients recovered from optic neuritis (visual acuity 0.8 or better). The programs differed in terms of the size of the stimulated visual field. One program tested the central 30 degrees and the other, central 8.4-degree visual field. It was found that the mean sensitivity tended to become higher when stimulating small field size in both normal persons and patients with optic nauritis. PMID- 1927322 TI - Topographical distribution of ocular surface cells by the use of impression cytology. AB - Cytology impression samples of the conjunctiva and the cornea were obtained from normal eyes. Our results were in agreement with most authors, except in the interpalpebral areas. In the interpalpebral areas, we found new data about superficial cell distribution not described before; the non-secretory cells were more separated and larger, with a higher nuclear-cytoplasmic ratio than other areas. The secretory cells (goblet cells) had significantly decreased with respect to the rest. In the interpalpebral areas, near the limbal areas, no goblet cells were found, and the size of non-secretory cells was increased, the density was lower and the nuclear-cytoplasmic ratio was higher, with regards to the external areas. The corneal epithelial cells had a similar morphological appearance in all specimens tested. We confirm that our subjects were absolutely normal, and conclude that environmental factors might explain why the cells were slightly transformed. PMID- 1927324 TI - Long-term changes in the outer part of the eye in welders. Prevalence of spheroid degeneration, pinguecula, pterygium, and corneal cicatrices. AB - Biomicroscopical examination of possible cumulative changes in the outer part of the eye in 217 male welders with variable welding exposure time showed conjunctival spheroid degeneration in 24% of the welders. The prevalence of changes was significantly increased in welders with the higher exposure time in an age-matched reduced material (98 x 2 eyes; respectively, over and under 40 h.y (number of daily hours of welding multiplied by number of years of welding), welders with stays abroad over one year being withdrawn. The prevalence was also increased in the latter group (41%, N = 40, against 21%, N = 177). Pinguecula was present in 57% of the welders, with a tendency towards larger area with increasing welding exposure. The frequency was increased as compared with that in a control material examined on a previous occasion (41%). Pterygium proper was found in only one subject, pseudopterygium in 5%. Corneal cicatrices were present in about one half of the subjects. The prevalence increased with increasing welding exposure (24% in subjects with short, 42% in those with long exposure; 98 x 2 eyes). Acute welding light keratopathy was experienced by 73%. The mean number of attacks in the 217 welders was 6.4. The frequency was highest in subjects with long welding exposure. The risk of chronic impairment of sight owing to cumulative welding light injuries is very little in the present material, since only 2% had spheroid degeneration on the cornea (only discrete, peripherally located); there was no preponderance of pterygium. On the other hand, the many foreign bodies on the cornea (cicatrices) constitute a risk that apparently does not decrease with increasing welding experience nor repeated attacks of welding light keratopathy. PMID- 1927323 TI - Work-related penetrating eye injuries. AB - A review of all penetrating eye injuries treated at the Manchester Royal Eye Hospital over 5 years (January 1st 1982 to December 31st 1986) was undertaken. There were 258 penetrating eye injuries of which 69 (26.7%) were due to work related accidents. All were men and 52 (75.4%) of them were under the age of 40 years. Hammering and chiselling were the commonest activities at the time of the injury and accounted for 25 cases (36.2%). Thirty-six patient (52.1%) had intraocular foreign bodies. Thirty-six patients (52.1%) achieved a good visual result (6/12 or better) and 9 had no perception of light, 7 of whom had enucleations. The period of inpatient treatment ranged from 1 to 26 days. From the analysis of the activities at the time of the injury, 61 injuries (88.4%) may be considered to be preventable with appropriate eye protection. PMID- 1927325 TI - Iris colour and the influence of local anaesthetics on pre-corneal tear film stability. AB - Using non-invasive methods we report here that the stability of the pre-corneal tear film is lower in the brown eye than in the blue eye. The average stability in the blue eye is 15.8 sec (SD +/- 5.8) and in the brown eye it is 12.3 sec (SD +/- 2.9). On average, instillation of topical anaesthetics, benoxinate hydrochloride (0.4%) or amethacaine hydrochloride (0.5%), depress the stability of the pre-corneal tear film in blue eyes but not in brown eyes. PMID- 1927326 TI - Serum beta-2 microglobulin and C-reactive protein levels in acute adenovirus conjunctivitis. AB - Serum beta-2 microglobulin and C-reactive protein levels were measured in 52 patients with acute adenovirus conjunctivitis and 58 healthy subjects, by ELISA technique. Serum beta-2 microglobulin levels were found to be significantly increased while there was no change in C-reactive protein levels. Serum beta-2 microglobulin levels closely paralleled the severity of the disease. The increased beta-2 microglobulin level in serum showed a significant fall to normal level on clinical improvement. There was no difference in the serum beta-2 microglobulin levels in virus-isolation positive and negative patients. PMID- 1927327 TI - Medulloepithelioma of the ciliary body. AB - Neuroepithelial tumors of the ciliary body occur more seldom than retinoblastoma. The congenital form is called medulloepithelioma, the adult-acquired adenoma or adenocarcinoma. Medulloepitheliomas consist of organoid epithelial structures developing anteriorly along surfaces such as the iris. The authors report on a congenital type unusually growing not only anteriorly along the lens, but also posteriorly along the retina's surface causing retinal detachment. PMID- 1927328 TI - Retinitis following disseminated cryptococcosis in a renal allograft recipient. Efficacy of oral fluconazole. AB - A case of retinitis following disseminated cryptococcus neoformans infection in a renal allograft recipient is reported. Therapy with oral fluconazole showed a remarkable improvement at the end of 8 weeks. This is the first report of the use of fluconazole in the treatment of cryptococcal retinitis. PMID- 1927329 TI - [Anterior arthrodesis of the inferior cervical spine]. PMID- 1927330 TI - The use of the Hartshill system for the cervical spine. AB - The Hartshill system is a modification of the Luque system for posterior segmental wiring of the spine and has for five years been our routine means of posterior spinal fixation throughout the spine from skull to sacrum and for all varieties of spinal disorders. This paper presents our experience with the use of the Hartshill system in the cervical spine. There have been 34 cases with a minimum two year follow-up (trauma 11, rheumatoid 8, facet osteoarthritis 7, tumor 5, congenital 2 and myelopathy 1). There has been only one serious complication. The system is essentially simple and inexpensive but, nonetheless, attention to detail in technique is important and this will be emphasized. Recent modifications of the Hartshill system for the cervical spine by Ransford and Fidler will be discussed. With proper attention to detail the Hartshill system provides a secure adaptable posterior fixation system that can be used throughout the cervical spine. PMID- 1927332 TI - [Anatomical bases of the surgical treatment with Cotrel-Dubousset material of fractures of the thoracic and lumbar spine]. PMID- 1927331 TI - [Total vertebrectomy for the treatment of tumors of the dorso-lumbar column]. PMID- 1927333 TI - Primary stabilization of spinal fractures with and without neurologic deficit. AB - This paper reports the results of our methods, describes the different approaches and shows the different techniques of implantation. To obtain stable fixation of the fracture we use three different types of implants, depending on the localisation. From C1 to C3, we use the new type of the Dens fixation plate. From C3 to Th1, we use the so-called doublewhole plate. Both plate types are fixed with so-called TKFS-screws. In the thoracic and lumbar region we have used up to now the Zielke USIS-system. To obtain a primary stable three-dimensional construction a dorsoventral procedure in one session is necessary. PMID- 1927334 TI - Anterior decompression and stabilization of thoracolumbar burst fractures using the Slot-Zielke-device. AB - A retrospective study was performed on 62 patients treated for thoracolumbar burst fractures. The Fracture Study Protocol of the Scoliosis Research Society was used for data collection. The first group consisted of 29 patients, treated between July 1983 and November 1986 with an one-stage operation consisting of anterior decompression by subtotal vertebrectomy, reduction and stabilization with the Slot-Zielke device. The mean follow-up was 3.1 years. The second group consisted of 33 patients, who were treated between November 1986 and November 1988. In this second group treatment was performed by an anterior decompression by subtotal vertebrectomy, reduction and stabilization with the Slot-Zielke device, in the same session followed by an additional posterior spondylodesis and instrumentation with the Zielke D.K.S.-system or by the Cotrel-Dubousset compression-rod system. Mean follow-up of this second group was 1.7 years. In all patients bony union occurred. Loss of reduction of more than 5 degrees occurred in 41% of the patients of the first group, but in only one patient (3%) of the second group. In both groups most patients with incomplete neurologic lesions improved postoperatively and were upgraded one or two steps on the Frankel-scale. No patient showed neurologic deterioration after surgery. In both groups a high percentage of patients were painfree at follow-up. The complication rate in both groups was low, despite the rather difficult anterior approach. Because of the high rate of loss of reduction in the first group of 29 patients and the low degree of flexion-bending loading and torsional stability in biomechanical evaluation in vitro of the Slot-Zielke device on human cadaver spine, an additional posterior stabilization of the spine after an anterior approach for anterior- and middle-column fractures should be considered. PMID- 1927335 TI - Treatment of infected arthrodesis of the ankle. AB - In arthrodesis of the ankle joint the use of external fixation can cause severe problems owing to pintrack infections. As long as infection is active, bony consolidation of the arthrodesis is delayed. In the potentially infected area a normal internal osteosynthesis is risky. Our treatment rationale comprises a two stage procedure with treatment of infection first by implant removal, thorough debridement and implantation of Septopal beads and then secondary internal stabilization with an antibiotic-releasing bone plate. Of the 42 cases amputation had to be performed in 3; of the remaining 39, infection was cured long-term in 36. In all 39 a stable bony fusion was achieved. PMID- 1927336 TI - The use of the Hartshill system for the internal fixation of spinal fractures and tumors. AB - We present the use of our Hartshill system for the posterior fixation of fractures and tumors. We present our first 69 fractures with a minimum two year follow-up (11 cervical, 8 thoracic, 42 thoracolumbar, 8 lumbar). The Hartshill system is a simple and secure method for the fixation of the spine in such cases. Both in thoracolumbar fractures and in tumours the common problem is collapse of the anterior column so that the spine is in kyphosis. Biomechanically the solution for the reduction and internal fixation in such cases is to use a fixation system which reduces the kyphosis by creating a lordosis. This is simply achieved with the Hartshill system. PMID- 1927337 TI - [Osteosynthesis of thoracic and lumbar vertebral fractures using Cotrel-Dubousset material (110 cases)]. PMID- 1927338 TI - [Value of a short osteosynthesis with pedicular fixation in the treatment of unstable dorso-lumbar spinal fractures. Biomechanical study and actual clinical results]. PMID- 1927339 TI - [The treatment of dorsal and lumbar spinal injuries using posterior plates screwed into the pedicle]. PMID- 1927340 TI - Current methods of dorsal spine fusion with pedical screws and presentation of a new method for treatment of fractures and low back instability. AB - A new instrumentation system, the H-frame system, has been developed for dorsal fusion in scoliosis, spinal fractures and degenerative low back problems. The basis is a prelinked slotted H-frame with two rods of 6-mm diameter with 5-cm threaded ends. There are 4 different lengths, solid in the middle and threaded at the ends. Connection with hooks and/or pedical screws is easy and stable. A slotted system using special conical nuts to grasp these hooks or screws tightly prevents loosening. For low back fusion in degenerative disease the slightly lordotic H-frame is connected to 4 screws. If needed, a sublaminar Luque wire may be added in between. Correction in lordosis with distraction or compression is possible. The fixation is very rigid in all directions with a minimum of implant material. For thoracolumbar fresh fractures 2 pedical screws are placed above and 2 screws below the fracture area, and an H-frame is inserted with one end fixed below and one end above the opposite side of the other rod. Because of the rotary section in the H-frame, the apparatus may be repositioned simply by pushing the frame with the two other screws under control of the H-frame cross-link connection. Distraction and correction of kyphosis is achieved with this simple movement at the same time. The total stable fixation needs no after-treatment. The method may also be used for scoliosis with a combination of hooks, screws and wires. Experience is still very limited. The apparatus has been used in the lumbar spine in more than 10 cases with over 6 months follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927341 TI - [Combined anterior and posterior arthrodeses in the treatment of spondylolisthesis. Apropos of a series of 45 cases]. PMID- 1927342 TI - In situ posterolateral fusion for spondylolisthesis. AB - In this series spondylolisthesis was treated operatively in children and adolescents who had a displacement greater than 50% even if they were asymptomatic. In youngsters with less than 50% displacement and in adults, operative stabilization was performed if the displacement was progressive or if there were persistent symptoms unresponsive to conservative treatment that interfered with the patient's normal activities. The operation consisted of a posterolateral fusion in situ. Usually a laminectomy was not performed unless there were signs of severe neural compression. No reduction of the spondylolisthesis was attempted. We reviewed 38 cases treated operatively with a mean follow-up of 7 years. Twenty patients were younger than 20 years at the time of operation and 10 of these had greater than 50% displacement. The results were good to excellent in 90% (18 patients). In the adult group (18 cases) the results were less favorable, but still good to excellent in 72% (13 patients). In the adult group pseudarthrosis frequently occurred at the L4-L5 level. There were no neurologic complications postoperatively. Fusion in situ for spondylolisthesis is a safe operation giving satisfactory results. PMID- 1927343 TI - The causes of subsequent arthrodesis of the ankle joint. AB - Between 1917 and 1984, we performed 217 arthrodesis of the ankle joint. Posttraumatic states were the cause of the osteoarthritis in 153 cases, whereas 118 of these cases were malleolar fractures. The accident X-rays were analyzed, and the fractures were classified in accordance with the classification of Weber (11). Our own system was used for the radiological classification of the degree of arthritis. The extent of malunion after the initial care was assessed. We found type-C malleolar fractures most frequently, the most striking malunion being the shortening of the fibula. In all fractures requiring subsequent arthrodesis, osteoarthritis of degree III-IV was present. In most cases the malleolar fractures treated surgically showed a shortening of the fibula and must be considered failures of initial care. The classification into types according to Weber also seems to provide prognostic information about the subsequent need for arthrodesis. Here it can be observed that C-fractures and compression fractures more often require arthrodeses. PMID- 1927344 TI - [Surgery of the intervertebral ligaments, alternative to arthrodesis in the treatment of degenerative instabilities]. PMID- 1927345 TI - [Comparative study of posterolateral and posterior lumbosacral arthrodesis with and without osteosynthesis]. PMID- 1927346 TI - Management of wound sepsis after spinal fusion surgery. AB - In wound sepsis after spinal surgery a first attempt to control infection without removal of the implants is justified, as implant removal after correction of scoliosis and kyphosis and in reduction of slipped vertebrae would often cause instability of the segments operated on. If the first revision is not successful, a second should not be delayed too long. Sometimes partial removal of the implants may be sufficient for infection control, thus maintaining a certain stability. We use local antibiotic treatment with Septopal chains, as suction irrigation sometimes is complicated by secondary bacterial contamination. By applying this treatment rationale we were able to control infection in 50 out of 53 patients with wound infection. PMID- 1927347 TI - Stabilization of the lumbosacral spine in postlaminectomy syndromes. Technique and 2-year results. AB - A 2-year follow-up study is presented using transpedicular stabilization with USIS (Universal Spinal Instrumentation System) and dorsoventral fusion for failed back syndrome. Eighty-four % excellent and good results at 3 to 6 months have decreased to 56% at 1 to 2 years. Complications are few if the anatomic landmarks are respected. Many psychological and social factors also modify the final outcome of salvage surgical procedures. Only the relief of pain determined our subjective evaluation by the patient himself, without regard to sensory or motor deficiencies. PMID- 1927348 TI - [Personal experience with Chopart's arthrodesis, according to Steinhauser]. PMID- 1927349 TI - [Echography and muscular injuries in athletes]. PMID- 1927350 TI - CT scan of the knee: correlation with clinical and arthroscopic findings. AB - CT was performed in a series of 150 consecutive clinically diagnosed meniscal lesions of the knee. Six to 12 contiguous slices, each 1 mm thick, were obtained starting from the tibial plateau and proceeding cranially to the intercondylar fossa. The medical imaging team was not informed of the medical history of the patients nor of the relevant clinical diagnosis. Arthroscopic findings were subsequently correlated with the CT findings. With the arthroscopic diagnosis defined as correct, a CT sensitivity rate of 80% was obtained. The specificity of the test was 93%. This study of 75 consecutive meniscal tears was designed to evaluate arthroscopic meniscal suturing using an inside-out technique. PMID- 1927352 TI - MRI and ultrasound evaluation of the shoulder. PMID- 1927351 TI - Correlation between magnetic resonance imaging and arthroscopy in the diagnosis of anterior cruciate ligament and meniscus lesions. AB - In both radiological and orthopedic journals the value of MRI for diagnosing internal derangement of the knee has been assessed recently. However, results vary widely and no study reports on the differentiation among types of ACL tears. As far as meniscal pathology is concerned, attention has been drawn by Reicher et al. (11) and Glashow et al. (5) upon the false positive tears of the posterior horn of the medial meniscus. Where most authors consider signal inversion in the posterior horn of the meniscus as a normal finding in children--due to the higher water content--the same fact in adults can be interpreted as a false positive image or a missed tear at arthroscopy (5). PMID- 1927353 TI - [Gradient-echo MRI of subacromial pathology]. PMID- 1927354 TI - Correction of severe foot deformities. AB - An arthrodesis between tibia and calcaneus was performed after extirpation of the lateral malleolus and the talus in 65 patients with severe stiff paretic feet in equinovarus position, 44 nonleprosy and 21 with leprosy. Early mobilization with weightbearing was allowed after 1 week. Bony fusion was achieved in 95% in the nonleprosy group and 76% in the leprosy group. The final appearance and function was very satisfying with a good range of motion in the Chopart joint. PMID- 1927355 TI - Correlation of computed arthrotomography with arthroscopy of the glenohumeral joint. AB - We report our experience with CT-arthrotomography, compared to the arthroscopic findings in a group of 54 non-selected patients with a shoulder problem. Thirty one patients had a CAT-scan of the shoulder and subsequently underwent a videotaped arthroscopy of the shoulder. Five out of the 10 negative CAT-patients were positive on arthroscopy for impingement syndrome. Arthroscopy picked up 5 partial thickness rotator cuff tears, not seen on CAT. Arthroscopy was also very helpful in diagnosing synovitis. For biceps problems, loose bodies, labrum tears and adhesive capsulitis, the sensitivity and accuracy figures were very high, comparing CAT-scan and arthroscopy. A shoulder with a history of instability or a painful clicking shoulder seems to be the best indication for CAT-scanning. PMID- 1927356 TI - Occipito-cervical fusion in rheumatoid arthritis. AB - Between 1977 and 1988 twenty-five patients with rheumatoid arthritis involving the cervical spine were treated by an occipito-cervical fusion. Twenty-two patients are included in this study. The main indications for surgery were intractable pain and progressive neural impairment. The operative procedure consisted of an H-bone graft fixed with steel wire in 19 cases, fusion of occiput C2 six times and of occiput-C3 thirteen times. A Hartshill-Ransford (5, 12) loop was used in three cases: occiput-C3 twice and occiput-C7 once. The mean duration of follow-up was 3 years 8 months in 17 patients. Improvement of symptoms and signs was achieved in 88%. There were 2 post-operative deaths. The high rate of pseudarthrosis in our series was confirmed by several authors. The loop technique provides a more stable fixation and will be our technique of choice in the future. PMID- 1927357 TI - Anterior cervical spine fusion in treatment of cervicobrachialgia. AB - Traumatic and degenerative changes in the spine at the level of the neck are frequent causes of pain in the neck, often associated with radiculopathy and sometimes even myelopathic symptoms. The signs and symptoms can generally be attributed to a problem of instability for which there are no specific criteria. If conservative treatment does not help, satisfying results can be achieved by a stable intercorporeal fusion using the modified Robinson technique. An EMG and a cervical myelogram must be carried out before surgical stabilization. In 154 patients followed for an average of 12 years, 75% observed resolution of the pain and paresthesias after surgical stabilization. These results correspond to those described in the literature. The best results are achieved if the signs and symptoms are experienced for no longer than 1 year and if the patient is under age 40. PMID- 1927358 TI - Vestibular and equilibrium research: basic and clinical implications. Proceedings of the sixteenth Barany Society meeting. Tokyo, May 28-30, 1990. PMID- 1927359 TI - Microtubule subunits of guinea pig vestibular epithelial cells. AB - Guinea pig cochlear supporting cells have microtubules which are composed of 15, instead of the ordinary 13, protofilaments. The microtubules form a large and stiff bundle involving abundant actin filaments to provide effective rigidity to the cell specialized for transduction of extremely high-frequent mechanical stimuli. We examined microtubules in guinea pig vestibular end organs with the transmission electron microscopy after treatment with tannic acid. Solitary microtubules occurred abundantly in the supranuclear region of type I hair cells, but sparsely in type II hair cells. Individual microtubules consisted of an ordinary set of 13 protofilaments in these hair cells as well as in the supporting cells. Supporting cells were characterized by cytoskeletal bundles of 2 to 30 microtubules which were found to be connected with actin filaments via cross-linking units. Results from the present investigation indicate that such less-organized microtubules of 13 protofilaments are sufficient for vestibular supporting cells which are specialized for detection of lower-frequency vibration together with fellow sensory cells. PMID- 1927360 TI - Anionic sites of the basement membrane of the labyrinth. AB - The presence of anionic sites in the labyrinth is demonstrated in this study, using polyethyleneimine as a cationic probe. Hartley-strain guinea pigs (200-300 g) with a normal Preyer's reflex were used. A 0.5% polyethyleneimine (PEI, MW 1,800) solution adjusted to pH 7.3 with HCl following Schurer's method was systemically administered through an axillary vein. In the cochlea, the presence of anionic sites was demonstrated on the basement membrane of the capillary wall in the stria vascularis. The presence of anionic sites was also confirmed on the basement membrane in Reissner's membrane but its density was much lower than that in the stria vascularis. In the ampulla and macula, the anionic sites were present on the basement membrane of the capillary wall and sensory epithelium. PMID- 1927362 TI - Vestibular pathology in a new-mutant mouse. AB - The histological characteristics of the vestibule in a strain of new-mutant mice were studied under light microscopy. These new-mutant mice, manifesting drawing back, circling, head-tossing and hyperactive behavior arose as a spontaneous mutation in the C3H/He stock. For our study, 36 of these mice ranging in age from 10 days to 18 months were used. At 10 to 15 days after birth, the vestibular gross anatomy was well-developed and all three cristae and two maculae were morphologically normal. Age-dependent degeneration of the saccular maculae was found to begin at 21 days, and almost all hair cells were missing at 90 days. Further, morphological changes in the utricular maculae appeared at one year, and a severe loss of hair cells was observed at 18 months. In contrast, the cristae ampullaris remained well preserved until the age of 18 months. The phenotype of the abnormal gene in these mutant mice correlates to the morphological abnormalities seen in the vestibule. PMID- 1927361 TI - Glycoconjugates in the otolithic organ of the developing chick embryo. AB - The presence of glycoconjugates in the otolithic organ of developing chick embryos was investigated histochemically using lectins. On the 6-day-old chick embryo, intense labelling with lectins was observed in the sensory epithelium, on the surface of the epithelium and on the immature otoconia. The otoconia were intensely labelled with lectins at every stage of the chick embryos, while the labelling with lectins in the sensory epithelium became weaker with the maturing of the otoconia. In TEM observation, the secretory granules of the supporting cells of the sensory epithelium were labelled with lectin. The reaction of lectin was more intense in the electronic dense zone of the otoconium than in the electronic lucent zone at every stage of the chick embryos. These findings indicate that the precursors of the otoconia are secreted by the supporting cells of the sensory epithelium and that glycoconjugates play an important role in otoconial formation. PMID- 1927363 TI - Inner ear microvasculature in normal and experimental hydrops. A scanning electron microscopic study. PMID- 1927364 TI - Modulation of the endolymphatic sac function. AB - A method for inducing a partial dysfunction of the endolymphatic sac and its effect was investigated. Acetazolamide as well as amiloride caused collapse of the lateral intercellular spaces in the endolymphatic sac epithelium and a subsequent mild endolymphatic hydrops. These changes indicate a decreased absorption rate of endolymph in the endolymphatic sac. Colchicine caused a disturbed secretory activity of the sac induced by glycerol. Animals treated with colchicine showed marked signs of inner ear malfunction after additional treatment with glycerol, which might indicate that the secretory activity in the sac is closely related to the regulation of inner ear fluid homeostasis and functional disturbance. PMID- 1927365 TI - Effect of gentamicin on vestibular ganglion. AB - The morphological changes of the vestibular ganglion induced by gentamicin (GM) were investigated using light, scanning and transmission electron microscopy. The guinea pigs were injected 4 mg of GM into the middle ear for 5 days. The vestibular ganglion was observed up to 4 weeks after the treatment. Three days after the treatment the degenerative change was first noted in the vestibular ganglion. The degenerative process started from the destruction of mitochondrial cristae and vacuolization of the cytoplasm of the Schwann cell. The cytoplasmic organelles in the ganglion cell gradually deteriorated with swelling of the endoplasmic cisterns as well as Golgi apparatus. At the later stage, the myelin sheath around the ganglion cell disappeared and the number of the cells reduced. These changes of the ganglion cell may be due to the direct action of GM. PMID- 1927366 TI - Pathohistological study with four kinds of stress stimulations on active endolymphatic hydrops in the guinea pig. PMID- 1927367 TI - The histologic characteristics of the core of the fissula ante fenestram. AB - In earlier studies of perilymphatic fistulae, we described their histologic criteria and the clinical criteria for the identification and prediction of patencies of the labyrinth capsule related to disorders of hearing and balance. These patencies were either of the fissula ante fenestram or of the round window niche-posterior canal ampulla fissure. The permeability of the fibrous core of a patent fissula ante fenestram has been questioned, authors of some earlier articles arguing that the tissue is loose, others that it is dense. This study demonstrates loose fibrous and cellular structure in the fissula's tract, dense collagen at the circumference. The loose arrangement of tissue suggests that fluid can pass through this patency, and it appears similar to that of the spiral ligament which has been shown to contain perilymph by way of intercellular communications with the perilymphatic space. PMID- 1927368 TI - Scanning electron microscopy and immunoglobulins of the endolymphatic sac in Meniere's disease. AB - SEM and immunoglobulin staining of the intradural portion of the endolymphatic sac (ES) were investigated. All 15 normal subjects, from fetuses to an 80-year old adult, showed well arranged epithelial cells. In Meniere's disease (all 15 patients) the ES showed various types degeneration of the epithelial cells. Inner ear deafness experimentally produced by kanamycin injection showed a similar degeneration of the ES. IgG of the ES in Meniere's disease showed moderately evident deposits compared with normal subjects. However, these findings were also found to the same degree as IgG deposits in animal deafness produced by KM injection. From the above results it can reasonably be concluded that the degenerated findings of the ES and deposits of the IgG in Meniere's disease may possibly be the result of cochlear deafness. PMID- 1927369 TI - Inner ear damage by local immune response of the endolymphatic sac in the guinea pig. PMID- 1927370 TI - Vascular permeability of the stria vascularis in experimental endolymphatic hydrops. AB - Vascular permeability of the stria vascularis was morphologically examined in hydrops animals, using the tracer method of horseradish peroxidase (HRP). The reaction product of HRP was observed in the capillary of the stria vascularis, not outside of it. The finding suggests that the vascular permeability of the stria vascularis is unchanged in Kimura's hydrops model. PMID- 1927371 TI - Cochlear strial blood circulation. AB - The present immunohistologic study demonstrates that cochlear strial blood circulation is markedly damaged in guinea pigs subjected to intense acoustic stimulation. In contrast, autonomic unbalance of the inner ear induced by resection or electric stimulation of the superior cervical ganglion has no appreciable effect on cochlear strial blood flow. In consequence, although strial blood circulation in the cochlea is susceptible to pathological change in some conditions, it does not appear to be affected by autonomic unbalance alone. PMID- 1927372 TI - Role of premotor vestibular nucleus neurons in vertical gaze. AB - The firing properties and projection patterns of secondary vestibular nucleus neurons involved in the vertical vestibulo-ocular pathways were investigated in alert cats. Recordings were made in the medial longitudinal fasciculus (MLF) from axons that were monosynaptically activated from the vestibular nerve. Many identified axons discharged in relation to vertical eye movements. The majority of these axons increased their firing rate for downward eye position (DPVs). During pitch rotation, the firing rate of DPVs was also related to upward head velocity, suggesting that they received monosynaptic input from the posterior canal. DPVs could be divided into two groups on the basis of their firing regularity. There was a tendency for regular DPVs to have a higher firing rate, a higher correlation for the rate-position relationship, and a larger phase lag and a smaller gain re head velocity than irregular DPVs. Spike-triggered average method and intraaxonal HRP techniques demonstrated that ipsilaterally projecting (i-) DPVs made inhibitory connections with up-on extraocular motoneurons, and contralaterally projecting (c-) DPVs made excitatory connections with down-on motoneurons. Virtually all i-DPVs were of regular type, while c-DPVs included both regular and irregular types. Stimulation of the caudal MLF at the level of the obex indicated that all the irregular c-DVPs and some of the regular c-DPVs had a collateral to the spinal cord, while none of the regular i-DPVs had such a collateral. PMID- 1927373 TI - Otolith function in hypo- and hypergravity: relation to space motion sickness. PMID- 1927374 TI - Generation of vertical and torsional rapid eye movement in the rostral mesencephalon. Experimental data and clinical implications. AB - The riMLF is a nucleus in the rostral mesencephalon whose bilateral destruction leads to a palsy of vertical and torsional rapid eye movements. A unilateral lesion leads to a loss of torsional rapid eye movements in only one direction, but vertical rapid movements can still be generated with some reduction in their velocity. Single neuron studies in monkeys and anatomy support the concept that the riMLF together with the PPRF are the critical areas in the brainstem to generate rapid eye movements in 3 dimensions. PMID- 1927375 TI - Vertical vestibulo-ocular reflex control after supranuclear midbrain damage. AB - The vertical vestibulo-ocular reflex (VOR) and its visual enhancement and cancellation were measured in patients with focal midbrain lesions that caused paralysis of upward, or upward and downward saccades. VOR gain was reduced in darkness during active vertical head pitch at frequencies from 0.25 to 2 Hz. Visual enhancement of the reflex by fixating a stationary target was subnormal upward and downward. Cancellation of the VOR was defective in both vertical directions during eye-head tracking. The VOR showed abnormal phase lead of the eyes in darkness, indicating that pretectal midbrain damage impairs the integration of eye velocity commands. PMID- 1927376 TI - Cat pontine omnipause neurons: direct inhibitory connection with Forel's field burst neurons participating in the genesis of vertical saccades. AB - This study investigates synaptic connections of omnipause neurons (OPNs) in the midline pontine tegmentum with vertical medium-lead burst neurons (BNs) in the Forel's field H (FFH), using the microstimulation and spike-triggered averaging techniques in chronically prepared alert cats. OPNs on both sides were antidromically activated by microstimulation at the recording sites of the BNs. Systematic tracking with the stimulating microelectrode revealed indications of profuse axonal branching of OPNs within the BN area. Antidromic spikes of the BNs evoked from the oculomotor nucleus and spike bursts of the BNs associated with saccades were suppressed by OPN area microstimulation. Averaged field potentials in the BN area triggered by spikes of OPNs showed monosynaptic positive waves. These results all but confirm the existence of direct inhibitory synaptic connections of OPNs with the BNs in the FFH. The role of OPNs in the genesis of vertical saccades was also discussed. PMID- 1927377 TI - The behaviour of burst neurons at high rotational velocities in the rhesus monkey. PMID- 1927378 TI - Saccadic eye movement deficits following ibotenic acid lesions of the nuclei raphe interpositus and prepositus hypoglossi in monkey. PMID- 1927379 TI - Vestibulo-thalamic neurons give off descending axons to the spinal cord. AB - Vestibulo-thalamic (VT) neurons were physiologically studied in the anesthetized cat. Forty-seven VT neurons were recorded extracellularly. More than half of the VT neurons responded monosynaptically to vestibular nerve stimulation while the others responded polysynaptically. They were activated antidromically from one or two sites in the VPL. VPM, VL, VM, SG, and PO of the contralateral thalamus. Four fifths of the VT neurons were activated from the C1 segment of the spinal cord. Half of them were also activated from the C4 segment, but none were activated from the L5 segment. It is suggested that most VT neurons project descending axons to the cervical spinal cord. Axonal branching was shown by means of systematic microstimulation in the thalamus and the ventral horn in the C1 segment. The VT neurons were mainly located in the descending vestibular nucleus. PMID- 1927380 TI - Combined analysis of horizontal and vertical optokinetic nystagmus reactions by means of ENG and brain mapping. PMID- 1927381 TI - Responses of neurons in the rat vestibular nuclei to static tilt stimulation. AB - The response properties of otolith afferent neurons have been analysed in the monkey and the cat. However, knowledge about the rat's responses to static tilt is scarce. To elucidate central information processing of the otolith system, responses to static tilt were analysed in the rat vestibular nuclei neurons. PMID- 1927382 TI - The otolith organ and the vestibulo-vegetative reflex. PMID- 1927383 TI - The role of cerebellar flocculus in adaptive gain control of ocular reflexes. AB - Sustained oscillation of the head of an alert animal with inphase or outphase combination of screen oscillation in the horizontal plane induced marked adaptive changes in the gain of the horizontal vestibulo-ocular reflex (HVOR). These changes are assumed to be a prototype of motor learning by the cerebellar flocculus. Several lines of experimental evidence, using rabbits or monkeys as experimental material, have consistently suggested that the plastic changes of neuronal activities of a particular group of floccular Purkinje cells (H-cells) are the sources of the HVOR adaptation. PMID- 1927384 TI - Eye movement control by Purkinje cell/climbing fiber zones of cerebellar flocculus in cat. AB - Direction of eye movement evoked by unilateral stimulation of the cerebellar flocculus was investigated by a video system with frame memory in ketamine anesthetized cats. Stimulation of the Purkinje cell zone in the vertical-plane unit on the right side evoked depression of both eyes combined with intorsion of the contralateral eye and extorsion of the ipsilateral eye, and stimulation in the horizontal-plane unit evoked abduction of the ipsilateral eye and adduction of the contralateral eye. PMID- 1927385 TI - Influence of vestibular and visual climbing fiber signals on Purkinje cell discharge in the cerebellar nodulus of the rabbit. AB - Extracellular recordings of the climbing fiber responses (CFRs) of single Purkinje cells were made in the cerebellar nodulus and ventral uvula of anesthetized pigmented rabbits. Natural vestibular and optokinetic stimuli were used to evoke responses from these Purkinje cells. Using a null response technique we sorted vestibularly-evoked CFRs into two canal-related categories. CFRs were related to either the ipsilateral anterior and contralateral posterior semicircular canal (iAC+cPC) or to the ipsilateral posterior and contralateral anterior semicircular canal (iPC+cAC). Both canal-related CFRs also responded to downward optokinetic stimulation. PMID- 1927386 TI - Effect of uvulonodular lesions on optokinetic nystagmus and optokinetic after nystagmus in cats. AB - To investigate the effect of uvulonodular lesions on horizontal optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN), 6 cats were tested before and after lesions made by ablation under anesthesia. In the 3 cats with only uvular lesion, the initial slow phase velocity and the time constant of OKAN were unchanged. In the remaining three cats whose lesions included not only the uvula but also the nodulus, the time constant of OKAN was markedly prolonged, and the initial OKAN velocity was not affected. The postoperative average time constant of OKAN increased from normal value of 9 s to about 40 s. In contrast, OKN was unchanged in all of the 6 animals. These findings indicate that the nodulus may contribute to the discharge characteristics of the velocity storage integrator. PMID- 1927387 TI - Positional nystagmus of benign paroxysmal type (BPPN) due to cerebellar vermis lesions. Pseudo-BPPN. AB - Positioning nystagmus accompanied by severe vertigo has been reported in patients with partial lesions of the inner ear, especially otolith lesions. Typically, this type of nystagmus shows a latent period and subsequent fatiguability. We concur with this finding and have constantly emphasized the significance of this phenomenon in clinical diagnosis. Since we started using CT-scanning, this type of nystagmus has been noted in 47 patients, all of whom had cerebellar vermis lesions. Attention should be focused on this association; if such a combination were seen in only 1 or 2 patients, it could simply be attributed to coincidence. But its occurrence in as many as 47 patients indicates a causal role of cerebellar vermis lesions. Its mechanism may be explained by incomplete inhibition of the vestibulo-oculomotor system including the cerebellar flocculonodular lobe or vestibulo-cerebellum. PMID- 1927388 TI - Cerebellar infarctions as the cause of 'vestibular neuritis'. PMID- 1927390 TI - Comparative investigation of vestibular influence on visual hallucinations and flash induced afterimage. PMID- 1927389 TI - EOG findings in patients with lesions in cerebellar peduncles. AB - EOG tests were performed in patients with lesions in either the superior or the middle cerebellar peduncle, because these patients showed cerebellar signs and symptoms and were difficult to distinguish from patients with cerebellar lesions symptomatically. EOGs of these patients showed a predominant decrease of pursuit gains and OKN velocity gains toward the lesioned side, whereas the percent reduction of fixation-suppression of caloric nystagmus decreased predominantly toward the side contralateral to the lesioned side, regardless of whether lesions were located either in the superior or the middle cerebellar peduncle. The present EOGs are best interpreted as a corresponding to a deficit of the neuronal events of the flocculus in the monkey and are solely ascribed to lesions in the cerebellar peduncles, because even well-defined cerebellar lesions on one side showed bilateral impairments of these visually induced eye movements. PMID- 1927391 TI - The effect of canal/visual and canal/otolith conflict on type I vestibular nucleus neurones. PMID- 1927392 TI - The influence of head position on the second phase of caloric nystagmus in rhesus monkeys. PMID- 1927393 TI - Effects of otolith stimulation in eccentric rotation on the vestibulo-ocular reflex in squirrel monkeys. AB - When a subject is rotated around an axis located behind his head (eccentric rotation, ECR), he experiences a combination of angular acceleration and two kinds of linear accelerations, tangential and centrifugal. The effects of stimulation of the otolith organs by linear acceleration in ECR on gain of the vestibulo-ocular reflex (VOR) were examined in squirrel monkeys. The VOR gain in ECR with the animal's head facing away from the rotation axis was significantly higher than that in centric rotation (CR) at 1.0 Hz, but not at 0.5 Hz. However, the VOR gain did not increase in eccentric-lateral rotation when the animal faced tangentially, even at 1.0 Hz. After bilateral ablation of the otolith organs (sacculectomy and utricular neurectomy), the VOR gain in ECR did not increase, even at 1.0 Hz. These findings demonstrate that tangential acceleration along the interaural axis in ECR stimulates the utricular maculae, resulting in enhancement of the VOR gain. The results also suggest that ECR is a useful clinical test for the function of the otolith organs. PMID- 1927394 TI - Vestibulo-ocular reflex suppression during high velocity head-free pursuit in normal subjects. AB - Recordings of head and smooth pursuit eye movement were made during head-free pursuit of a pseudo-random target motion stimulus. The pseudo-random stimulus was composed of 2 high velocity sinusoids, of frequency 0.4 and 1.3 Hz, with the velocity of the higher frequency being varied as a ratio of the lower frequency velocity between 0 and 2. Slow-phase gaze velocity gain for the lower frequency component decreased significantly with an increase in velocity ratio, and with an increase in target velocity above 60 degrees/s. Gaze velocity gain was frequently less than head displacement gain which remained fairly constant, indicating that the eyes had been driven in the opposite direction to head movement as a result of inability of suppress the vestibulo-ocular reflex. Similar effects were seen when visual feedback was degraded by tachistoscopic illumination of a target composed of 2 low velocity sinusoids (0.11 and 0.13 Hz). These results indicate that visual feedback, rather than head displacement, is essential for suppression of slow-phase vestibular eye movement during head-free pursuit, even at high stimulus velocities. PMID- 1927395 TI - Linear acceleration and horizontal eye movements in man. PMID- 1927396 TI - Linear vestibulo-ocular reflex (LVOR) and modulation by vergence. PMID- 1927397 TI - Spatial orientation of VOR to combined vestibular stimuli in squirrel monkeys. AB - The interaction of angular and linear stimuli produces a complex alignment of spatial orientation and the VOR. This phenomenon was studied by measuring three dimensional eye movements in 6 squirrel monkeys during centrifugation in the dark. The axis of eye rotation was always aligned with gravity and with the spinal axis of the upright monkeys. The erect monkeys were oriented such that they were either facing toward the direction of motion or were facing away from the motion. Angular velocity trapezoids were utilized as the motion stimuli with a ramp acceleration of 10 degrees/s2 to a constant velocity of 200 degrees/s. This yields a final centripetal acceleration of 1 g. The orientation of centripetal acceleration dramatically altered the VOR by changing the axis of eye rotation, the peak value of slow phase eye velocity, and the time constant of per rotary decay. The axis of eye rotation always tended to align with gravito inertial force, the peak value of slow phase eye velocity was greater when the monkey faced the motion than when it faced away from the motion, and the time constant of decay was smaller when the monkey faced the motion than when it faced away from the motion. These findings were statistically significant (p less than 0.05) and were consistent across all monkeys. The data also indicate that the VOR may be separated into two reflexes, a linear reflex and a rotational reflex. The linear reflex decays as the axis of eye rotation aligns with gravito-inertial force (GIF). These results indicate that GIF is resolved into two components: one representing an internal estimate of linear acceleration and one representing an internal estimate of gravity. PMID- 1927398 TI - Velocity dependence of the vestibulo-ocular reflex over a broad frequency range. PMID- 1927399 TI - Evaluation of the vestibulo-ocular reflex by high-frequency head oscillation. PMID- 1927400 TI - The aging vestibulo-ocular reflex (VOR) and adaptive plasticity. PMID- 1927401 TI - Spatial stimulus interference upon ocular movements investigated by means of the calorization pendulum interference test (CPIT). PMID- 1927402 TI - Effect of water immersion on post-rotatory and caloric nystagmus. AB - Caloric nystagmus and post-rotatory nystagmus were recorded with and without head out water immersion. As water immersion reduces body weight by about 90% owing to buoyancy, it decreases somatosensory inputs. Thus water immersion can be used to simulate a weightless environment. Caloric nystagmus was enhanced significantly by water immersion; however, post-rotatory nystagmus was not. These findings demonstrate that caloric nystagmus is easily affected by water immersion which decreases somatosensory inputs, but that post-rotatory nystagmus is not. PMID- 1927403 TI - Transient deviation of closed eye on head torsion. A kind of neck-ocular reflex. AB - Electrooculographically, torsion of the head with closed eyes causes little appearance of VOR, but a transient ocular deviation (TOD) of about 30 degrees and a maximum velocity of not less than 200 degrees/sec. TOD occurs more significantly during torsion of the head alone than during rotation of the whole body, with a two-fold greater degree of deviation, suggesting the importance of the input from the cervical afferent. TOD occurs even in a condition in which torsion of the head is made to try with the head fixed and as a result of this maneuver, a torsional force is put on the neck toward the direction of head torsion, but the head does not rotate (vestibular afferent is inoperative). Thus, it is supposed that TOD occurs as a result of the fact that the lateral gaze center is activated by perception of the directional information of head torsion from the cervical afferent. PMID- 1927404 TI - Response of medullary reticular neurons of cat to off-vertical axis rotations. AB - To investigate whether neurons in the medullary reticular formation of decerebrate cats can encode spatial orientation during 360 degrees off-vertical axis rotations (OVAR), responses of these units were studied during constant velocity OVAR in clockwise (CW) and counter-clockwise (CCW) directions. Tilt sensitive units, some of which were activated by antidromic stimulation of the thoracic cord, were found to respond to 360 degrees OVAR with position-and direction-dependent modulation in discharge rates. For the individual responsive unit there was a difference in the spatial location of the CW and CCW discharge maxima, while a comparable response gain was obtained for rotations in either direction. The orientation of the best response of each unit was not significantly modified by changes in the amplitude of head tilt and/or velocity of rotation. Such characterized directional axes of the medullary reticular units were found to have a fairly equal distribution over the 360 degrees. The role that neurons in the medullary reticular formation plays in encoding otolith inputs with respect to head movements is discussed. PMID- 1927405 TI - Multisensory integration in the human vestibular velocity storage mechanism? AB - To test the hypothesis that auditory inputs can interact with the optokinetically or vestibularly-charged human VSM, we examined the effects of sound on rotational nystagmus and HOKAN. Subjects were rotated at 60 degrees/s, in either clockwise (CW) or counterclockwise (CCV) direction, for a total of 3 min. After 1 min of constant rotation, the optokinetic surround (7 ft dia., 2 degrees stripes at 18 degrees intervals) was illuminated for 60 s and the ensuing HOKAN was recorded for 60 s (standard DCEOG). The chair was stopped 60 s later and the post-rotatory nystagmus (PRN) was recorded. The acoustic stimulus (4/s, 10 ms pulses) was presented to the subject by a loudspeaker in 4 randomized test conditions: (1) fixed to the surround-on during OKN, off during OKAN (2) fixed to the surround off during OKN, on during OKAN (3) rotating with the subject-on during OKN, off during OKAN (4) rotating with the subject-off during OKN, on during OKAN. In all conditions, the sound was on during per- and post-rotatory nystagmus. Each test was performed on a different day and consisted of 4 randomized control and test trials (CW and CCW). Under none of the above conditions was the rotatory or optokinetic decay affected by the presence of stationary or rotating sound. This absence of alteration of PRN by sound cues contradicts that reported by Kollar et al. (1988). Our evidence that neither HOKAN nor post rotatory nystagmus decay is affected by sound cues supports the conclusion that, under our conditions, multisensory interaction does not occur in the human VSM. PMID- 1927406 TI - Effects of tonic neck stimulation on caloric nystagmus. PMID- 1927407 TI - Locomotion and motion sickness under horizontal and vertical reversal of vision. PMID- 1927408 TI - Head stabilization during locomotion. Perturbations induced by vestibular disorders. AB - Head kinematics was studied in 10 normal subjects (NS) and 7 patients (P) with bilateral vestibular deficit while they executed various locomotor tasks. The movement of the body was recorded with a video system which allowed a computer reconstruction of the motion of joint articulations and other selected points on the body in three dimensions. Analyses focus on head translation along the vertical axis and rotation in the sagittal plane. Two conditions were studied: free walking (W) and hopping (H). The subjects were tested in light and in darkness. In NS, while walking in darkness, mean head position was tilted downward. In contrast, this flexion was not systematic in P. Darkness did not significantly influence the amplitude and velocity of head angular displacement during W, but, during H the amplitude decreased by 37% for NS. During H in darkness, head stabilization decreased for P. These results suggest that head kinematics, during natural locomotor tasks, could be used to evaluate vestibular deficiencies. PMID- 1927409 TI - Studies on vestibulo-spinal reflexes by examination of labyrinthine-evoked EMGs of lower limbs. AB - Evoked electromyograms (EMGs) induced by galvanic stimulation of the labyrinth were examined in the muscles of the lower limbs. The labyrinthine-evoked EMGs appeared in the muscles of the femoral and gluteal regions and of the legs, and these muscle activities were changed by the head position in spite of the labyrinthine stimulation being the same. The vestibulo-spinal reflexes fulfil these functions in coordination with the neck proprioceptor. PMID- 1927410 TI - The vestibulo-collic reflex induced by external ear canal irrigation. PMID- 1927411 TI - Human and animal semicircular canal function during circular walking. AB - It is generally accepted from animal studies that the medial vestibulospinal tract originates in the medial vestibular nucleus, which is supplied from the semicircular canals, and descends only to the upper thoracic levels of the cord. In humans, however, there is some indirect evidence to support the concept that impulses from the semicircular canals reach the lumbosacral cord and influence lower as well as upper extremity activity. PMID- 1927412 TI - Eye movement elicited by linear acceleration. PMID- 1927413 TI - The assessment of predictive effects in smooth eye movement control. AB - Predictive mechanisms in pursuit were studied by requiring subjects to track a moving target which appeared for a brief period (40-320 ms) at regular intervals. With successive presentations the timing of the eye velocity trajectory became progressively more predictive of target appearance, whilst simultaneously increasing in peak velocity. Sudden changes in periodicity or velocity resulted in inappropriate eye movements correlated highly with previous stimulus cycles. The results suggest that prediction involves storage of velocity information and its release under the control of a periodicity estimator. PMID- 1927414 TI - Analysis of smooth pursuit by the fast Fourier transform. AB - Eye movement during smooth pursuit examination was converted to digital values and analyzed by the fast Fourier transform (FFT). It was found that the power spectra differences between the eye and target movements at 0.3 Hz were significantly lower in the pathological pursuit patterns (saccadic and ataxic pursuit patterns). In addition, sums of the power spectra difference above 0.3 Hz were significantly greater in pathological pursuit patterns. PMID- 1927415 TI - Linear and angular optokinetic nystagmus in labyrinthine and central nervous system lesions. PMID- 1927417 TI - Analysis of the fast phase of per-rotatory nystagmus. AB - We studied the relationship between the fast phase velocity and amplitude of per rotatory nystagmus resulting from constant angular acceleration and deceleration stimulation. The relationship was nonlinear and was best fit to the exponential equation. We established the uppermost point of the data distribution along the resolution curve. In normal subjects the angular rotatory stimulation using a computer-controlled rotatory chair (ROKOS-6) with 5 degrees/s2 rotation was the best among three kinds of angular rotatory stimulation (1.2 and 5 degrees/s2). Compared to peripheral vestibular disorder the uppermost point of nystagmus had a tendency to be larger in amplitude in some cases with central vestibular disorder. In many cases with sudden deafness the same tendency was seen. PMID- 1927416 TI - Primary position upbeat nystagmus. Clinicopathologic study of four patients. AB - We report an electro-oculographic study (EOG) of upbeat nystagmus and neuroradiological correlations in 4 patients and neuropathological findings in 1 patient. All 4 patients revealed responsible lesions in the lower pontine tegmentum. The EOG data suggest that our patients had a deficit in vertical smooth eye movement balance. The nystagmus stopped or reversed direction during convergence or changes of head position. These EOG findings might be caused by vertical imbalance in the otolithic ocular reflex, superimposed on an imbalanced vestibulo-ocular reflex (VOR), secondary to a damage to the pontomedullary tegmentum. PMID- 1927418 TI - Upbeat nystagmus in primary eye position. PMID- 1927419 TI - Analysis of neuro-otological manifestations in patients with upbeat or downbeat nystagmus. PMID- 1927420 TI - Eye movement and neuronal response in the region of the interstitial nucleus of Cajal during sinusoidal vertical linear acceleration in alert cats. AB - We examined neuronal behavior and eye movement response to sinusoidal vertical linear acceleration in the INC region. In light, robust eye movement response with near compensatory phase was consistently evoked over wide frequencies. Without visual inputs, the linear vestibulo-occular reflex (LVOR) with advanced phase was inconsistently evoked. Optokinetic stimulation alone produced more lag of response phase as stimulus frequency increased, suggesting that the otolith inputs contributed to the eye movement response with near compensatory phase in light. The activity of all burst-tonic (BT) neurons tested which showed close correlation with spontaneous vertical eye movement was modulated during linear motion in light and during optokinetic stimulation in association with eye movement responses. Without visual inputs, similar linear motion produced no response in a majority of BT cells even when the LVOR was evoked. These results suggest that BT cells are involved in some aspect of the generation of a functionally important vertical eye position signal using the otolith and visual inputs. Many cells in the INC region that did not belong to BT cells responded to linear acceleration without visual inputs and optokinetic stimulation even when eye movement response was not evoked, indicating that these cells received the otolith and visual inputs. PMID- 1927421 TI - A case of acquired nystagmus alternans associated with acute cerebellitis. AB - A case of acquired nystagmus alternans (alternating nystagmus) is reported. The patient was a 14-year-old boy who presented with fever and headache, followed by dysbasia, truncal ataxia, and positional vertigo. Neuro-otological examinations revealed spontaneous downbeat nystagmus, bilateral gaze nystagmus and rebound nystagmus. Both cell count and protein volume were elevated in the cerebrospinal fluid, and a diagnosis of cerebellitis was made. About one month later, nystagmus alternans was observed, but it disappeared after 7 months. The presence of spontaneous downbeat nystagmus, rebound nystagmus, as well as cerebellar signs indicated that a cerebellar lesion was mainly responsible for the nystagmus alternans in this patient. PMID- 1927422 TI - "Telemetric" electronystagmography: a new method for examination of nystagmus outside the clinic. AB - The diagnosis of the vestibular system is expanded by an newly developed system. It offers mainly two additional ways for the examination of eye movements: 1) Time and place independent, telemetric ENG recording by the patient himself. 2) Simultaneous visual examination of the nystagmus and ENG recording in clinic and surgery. The device contains of special, handy ENG recorder with digitalized storing of ENG curves. For easy application, special goggles with pre-installed electrodes have been combined with modified Frenzel's glasses. The recorded curves can be evaluated with the aid of a regular personal computer. PMID- 1927423 TI - Analysis of saccadic eye movements using an infrared video system in human subjects. AB - Horizontal and vertical saccades were recorded and quantitatively analyzed with an infrared video recording system in 6 normal human subjects. Peak and mean saccade velocities increased exponentially as the amplitude increased. Peak velocity of horizontal saccade was significantly larger than that of vertical saccade (p less than 0.05, ANOVA test). On the other hand, duration and latency showed a linear relationship with saccade amplitude. Latency was constant (i.e. 0.21 s) irrespective of saccade amplitude in the regular eye tracking mode; however, latency slightly increased as the amplitude became larger in the randomized eye tracking mode. As a result, a slight positive correlation could be found between saccade amplitude and latency: r = 0.50 and 0.35 in horizontal and vertical saccades, respectively. PMID- 1927424 TI - Computer analysis of the optokinetic pattern test in acoustic tumors, brain stem and cerebellar lesions. Slow and fast phase velocities of optokinetic nystagmus. AB - Optokinetic pattern (OKP) abnormalities in 36 patients with infratentorial lesions were analyzed by microcomputer (7T18 Nihondenki-Sanei). The parameters used for analysis consisted of slow phase velocity (S-VEL) and fast phase velocity (F-VEL) in optokinetic nystagmus. In 16 patients with acoustic tumors, S VELs were normal or borderline when the tumors were less than 2 cm in diameter, but when the tumors were more than 2 cm, S-VELs were severely impaired. In 20 patients with brain stem and/or cerebellar lesions, S-VELs were abnormal in all the patients with the exception of 3. F-VEL abnormalities were seen in only 5 patients with brain stem lesions, especially pontine lesions. These findings suggest that S-VEL is a sensitive indicator of infratentorial lesions and F-VEL an important indicator of pontine lesions. PMID- 1927425 TI - Normative data for human smooth pursuit responses to horizontal step-ramp targets. PMID- 1927426 TI - Computer analysis of optokinetic pattern test for patients with localized lesions of unilateral frontal eye fields. AB - Four patients with localized lesions of the left frontal eye field as demonstrated at autopsy or MRI were studied. Their electronystagmography (ENG) recordings, which were induced by optokinetic stimulus, were analyzed by computer. Four factors were calculated by the ENG analyzing program. We conclude that the asymmetry of OKP in patients with localized lesions of the unilateral frontal eye fields is primarily caused by impaired S-VEL and F-VEL of the contralateral OKN compared with the side of the frontal eye field lesion. PMID- 1927427 TI - The effect of age on the visuo- and vestibulo-ocular reflexes of elderly patients with vertigo. AB - To evaluate the effect of age and vestibular deficit on the vestibulo-ocular and associated visual reflexes, rotating chair (VOR), eye tracking test (ETT) and optokinetic (OKN) responses were investigated using comparisons between three populations: young normals, vertiginous elderly patients, and age-matched normal elderly subjects. The gain of ETT and OKN responses were reduced for both elderly populations as compared to young normals, but less so for the vertiginous elderly. VOR gain was more significantly reduced in the vertiginous elderly, though VOR time constant was as reduced as for the normal elderly. These results indicate that visual inputs, even in the elderly, are probably employed to compensate for a vestibular deficit. PMID- 1927428 TI - Amino acid assay of vestibular nuclei 10 months after unilateral labyrinthectomy in squirrel monkeys. AB - Amino acids were assayed by HPLC in bilateral vestibular nuclei from normal squirrel monkeys (n = 3) and those 10-month post-unilateral labyrinthectomy (n = 4). Findings of vestibulo-spinal and vestibulo-oculomotor functions were identical for both groups. No left-right asymmetry of amino acids was found within either group, nor between groups with the exception of GABA: GABA was significantly reduced in the bilateral vestibular nuclei of the 10-month post lesion animals. This may be indicative of a reduction of cerebello-vestibular inhibitory control which could be secondary to the reduction of excitatory inputs to the system. PMID- 1927429 TI - Unilateral vestibular neurectomy in man causes a severe permanent horizontal vestibulo-ocular reflex deficit in response to high-acceleration ampullofugal stimulation. PMID- 1927430 TI - Recognition of the vestibular compensation with the vestibular-index after removal of acoustic neurinomas. PMID- 1927431 TI - Documentation of the recovery course and deficit side localization of an acute unilateral vestibular deficit using four-quadrant diagrams of slow phase velocity. AB - The horizontal vestibulo-ocular reflex was studied in normals and in patients with an acute or compensated unilateral peripheral vestibular deficit (PVD) in order to determine the efficacy of various response measures of deficit side and central compensation for high rotation velocities. The profiles of whole body rotation and the visual fixation period was chosen to yield slow phase velocity (SPV) profiles comparable with those obtained with caloric irrigation. The chair rotation direction producing the smaller amplitude of slow phase velocity measured over culmination period obtained with 40 s of 5 degrees/s2 constant acceleration to 200 degrees/s represented a lateralizing sign of all acute, and 85% of all compensated PVD cases. PMID- 1927432 TI - Compensatory otolithic slow phase eye movement responses to abrupt linear head motion in the lateral direction. Findings in patients with labyrinthine and neurological lesions. PMID- 1927433 TI - Monocular and binocular visual suppression of vestibular nystagmus. PMID- 1927434 TI - A model of cerebellar-brainstem interaction in the adaptive control of the vestibuloocular reflex. PMID- 1927435 TI - Postural compensation of congenital or early acquired vestibular loss in hearing disabled children. PMID- 1927436 TI - Compensatory process of vestibular neuronitis. From findings of combined galvanic test and caloric test. AB - The compensatory process of vestibular neuronitis in 7 patients was followed up and evaluated using the Combined Galvanic Test (CGT) and other neuro-otological data. CGT is the simultaneous recording of both galvanic eye movement (GEM) and galvanic body sway (GBS), and has proved to be reliable in the diagnosis of retrolabyrinthine disorders. The results were as follows: The subjective symptoms remained in 3 cases from 1 month to 1 year. The recovery of the GBS response was seen earlier than that of both GEM and caloric responses. The recovery of GEM and caloric responses was observed at almost the same time. We observed the favorable recovery process of caloric response and GEM response in some cases which had recovery of GBS response within 4 weeks and suggest that the system of GBS response is different from that of GEM and caloric response. However, the systems of the latter two may be the same. We assume that the recovery of GBS response is earlier than that of GEM and caloric responses because the otolithic system recovers more easily than the semicircular canal system. The CGT and caloric test were reliable in examining the compensatory process of vestibular neuronitis. PMID- 1927437 TI - Recovery of VOR and gaze disturbance after acoustic neuroma surgery. PMID- 1927438 TI - The relation between motor function development and vestibular function tests in four children with inner ear anomaly. AB - It is well known that the development of motor function is frequently retarded in children with congenital deafness, particularly in cases of inner ear anomaly. The relation between the results of vestibular function tests and the development of motor function in 4 children with inner ear anomaly is studied. CT scan obtained from these cases revealed the absence of lateral semicircular canals in both ears. There were no responses to caloric stimulation using 40 ml ice-water. However, damped rotation test elicited per-rotatory nystagmus in all cases. In contrast to this result, the same nystagmus was provoked only in 2 cases in Barany rotation test. Early development of motor functions, especially that of first walk, was more retarded in the 2 cases showing no per-rotatory nystagmus in Barany rotation test than in the other 2 positive cases. PMID- 1927439 TI - Ataxia induced by acoustic stimulation on force platform. Results on patients with hearing loss and/or vestibular lesion. PMID- 1927440 TI - Divergent nystagmus: recordings from an advanced system of infra-red oculography. AB - Because of some limitations in photoelectric nystagmography, a new system of binocular infra-red oculography (BIRO) was developed. The advantages of BIRO are excellent linearity up to +/- 20 degrees horizontal eye movement, sensitivity of at least 0.1 degree of eye movement and the possibility of obtaining binocular recordings. In the course of a routine clinical evaluation, divergent nystagmus was recorded in 2 patients. This occurred both spontaneously and following caloric stimulation. A vascular brain stem pathology was strongly suspected from magnetic resonance imaging (MRI) studies. The possible mechanisms of divergent nystagmus are discussed. PMID- 1927441 TI - Three components analysis of eye movements using computerized image recognition. PMID- 1927442 TI - Observation of eye movement with noctovision. AB - A two-channel new noctovision system is reported. The adoption of a small CCD infrared camera, noctovision has become convenient for clinical use as Frenzel's glass. The composition of system and 7 clinical cases are reported. PMID- 1927443 TI - Computer analysis of sinusoidal eye movements using pattern recognition. PMID- 1927444 TI - Optokinetic after-nystagmus as an indicator of a vestibular side difference. PMID- 1927445 TI - Ocular tilt reaction: clinical sign of vestibular lesion. PMID- 1927446 TI - Meyer zum Gottesberge's head-shaking test for the evaluation of jumbling. AB - Jumbling consists of loss of vestibular eye movement reflexes and resultant oscillopsia during movement of the head. This results in a failure of clear vision during head movement. The head-shaking test for evaluation of the jumbling phenomenon was initially suggested by Meyer zum Gottesberge in 1952. In this test, binocular visual acuity is measured while the patient shakes his head at a rate of 2 or 3 movements per second, 10 to 20 degrees horizontally or vertically, and compared head still position. In normal subjects, only a slight decrease in visual acuity is noted due to this head-shaking. A diagnosis of jumbling is made when the visual acuity during head-shaking is less than half the visual acuity when the head is held motionless. When the visual acuity during head movement is expressed as a percentage of the value obtained while the head is motionless, a quantitative evaluation of jumbling is possible. This test should be done at regular intervals especially on patients who receive parenteral administration of ototoxic aminoglycosides for an early detection of jumbling and an appropriate discontinuation of the drugs, along with repeated auditory testing. The test is also useful in monitoring recovery from jumbling. PMID- 1927447 TI - Low-pressure chamber test in Meniere's disease. AB - Lowering of the ambient pressure has been reported to have a positive effect on the symptoms in Meniere's disease. In order to further investigate this hypothesis the symptoms in the long-term span were studied in 54 Meniere patients who had undergone low-pressure chamber tests. Lowering of the ambient pressure can induce a temporary but not a permanent hearing improvement in patients with Meniere's disease. The results also indicate positive effects on other symptoms in Meniere's disease, but this could not be statistically proven. PMID- 1927448 TI - Vestibular evoked potentials to angular acceleration in the guinea pig. A preliminary report. AB - Rotational evoked potentials were studied in the guinea pig under urethane anesthesia. The stimulus events were triangular velocity changes produced by abrupt reversals of acceleration, and horizontal semicircular canals were stimulated. A positive-negative-positive wave was recorded in the vestibular nuclei and the potential was totally abolished after bilateral labyrinthectomy. Single unit recordings revealed that the peak latency of the negative wave is almost coincident with the peak latency of the excitation of type I vestibular nucleus neurons. It is concluded that the recorded potential to the rotational stimuli in this experiment is of vestibular origin. PMID- 1927449 TI - Investigation of vestibular damage by antituberculous drugs. AB - Vestibular function testing was performed regularly on patients who were administered streptomycin, kanamycin, or enviomycin, and vestibular damage was detected at an early stage, and quantitatively. We investigated the point in time at which the therapy should be discontinued. Subjects consisted of 204 cases of tuberculosis treated with streptomycin, kanamycin, enviomycin. They were admitted to the hospital between December 1984 and August 1989. Twenty-eight cases of vestibular dysfunction due to streptomycin, kanamycin, and enviomycin could easily be detected at an early stage by performing Meyer zum Gottesberge's head shaking test for the evaluation of jumbling, together with Romberg's test and the stepping test. All cases who had vestibular dysfunction completely recovered because of early detection. In addition, 7 cases recovered afterwards from temporary vestibular damage shown only in Meyer zum Gottesberge's head-shaking test (abnormality of vestibulo-ocular reflex was only detected and vestibulo spinal reflex remained intact), despite continuation of streptomycin injection. When the results of the head-shaking test are less than 50% and when a sway and/or rotation in the stepping test occurs, the injections should be discontinued. PMID- 1927450 TI - Detection of the unilateral vestibular recruitment phenomenon using the rotation test. AB - The possibility of detecting unilateral vestibular recruitment using the rotation test was examined. According to the analogy model of cochlear recruitment, the directional difference of rotation nystagmus reaches its maximum at the threshold stimulus intensity of the affected ear when recruitment is present, and the predicted maximum directional difference remains within the normal variation range when the contribution from the spontaneous nystagmus is removed. Moreover, there was no difference in the positive ratio of recruitment in the rotation test between the two groups evaluated as having positive and negative recruitment on the caloric test. From these results, detection of the unilateral vestibular recruitment phenomenon, when similar to the cochlear recruitment, was concluded to be difficult using the rotation test. PMID- 1927451 TI - Cranio-corpo-graphy patterns in patients with acoustic neurinoma. PMID- 1927452 TI - Comparative study of computerized trapezoid rotation test and sinusoidal harmonic acceleration test. AB - By using the Contraves computerized rotary chair system, trapezoid rotation (TR) test and sinusoidal harmonic acceleration (SHA) test were performed on each subject on the same day. The results in 25 normal volunteers and 145 patients with peripheral vestibular disorders were as follows: 1) As regards directional preponderance, the results of two rotation tests agreed in 75.9% of all patients, but a discrepancy was found in the rest. Abnormality was detected by TR test in 57.2% of all patients, and, less frequently, in 45.5% by SHA test. 2) In normal subjects, the maximum slow phase velocity of nystagmus provoked by TR test was greater than that of nystagmus provoked by SHA test using angular acceleration of a magnitude comparable to that in TR test. 3) As to the detection of abnormal VOR gain, the results of two rotation tests agreed in 100% of patients with bilateral vestibular disorders. However, in patients with unilateral vestibular disorders, the detection rate was higher for SHA test than that for TR test. PMID- 1927453 TI - Visual suppression test using post-rotatory nystagmus. Clinical course in patients with motion sickness. AB - With the results of VS test (%) we were able to classify patients into three groups as follows: Group I, hyper range of visual suppression, VS (%) = 100-90; Group II, normal range of VS (%) = 89-45; Group III, reduced or abolished range of VS (%) = less than 44. The results with VS test using post-rotatory nystagmus (PRN) were in Group I 58 cases, in Group II 28 cases and in Group III 1 case, and using caloric nystagmus (CN) the results in Group I were 39 cases, Group II 29 cases, and Group III 1 case. With the correlation of VS test between PRN and CN we were able to classify patients into four types as follows: Type I, hyper range of VS in both PRN and CN; Type II, hyper range of VS in PRN; however, normal range of VS in CN; Type III, normal range of VS in both PRN and CN; Type IV reduced or abolished range of VS in both PRN and CN. It was very interesting in the clinical course of motion sickness that patients under 11 years of age (18 cases) of Type I (31 cases) showed marked improvement to Type III (11 cases) at the time of disappearance of symptoms; however, patients over 12 years of age (13 cases) of Type I remained stationary Type I (9 cases) at the time of disappearance of symptoms. PMID- 1927454 TI - The acute effects of unilateral vestibular neurectomy on sensory and motor tests of human otolithic function. AB - Patients were tested 1 day before and 1 week after therapeutic unilateral vestibular neurectomy (UVN) on vestibular tests which are likely determined primarily by otolithic function. UVN causes a maintained ocular torsion: fundus photographs showed that both eyes of every patients were rolled such that the upper pole of both eyes was tonically deviated towards the operated side, and there is a corresponding change in the perceived gravitational horizontal: patients set a small bar of LEDs bar down on the same side as their operation. One week after UVN, patients showed an asymmetrical sensitivity to linear acceleration vectors directed along their interaural axis in comparison to their preoperative settings for the same stimuli. PMID- 1927455 TI - Psycho-vegetative responses in vertiginous patients. PMID- 1927456 TI - The beginning of Meniere's disease. AB - Sudden deafness and low-tone hearing loss were treated by steroid therapy. Of the 106 cases of sudden deafness, 23 (21.7%) showed complete recovery, 36 (34.0%) remarkable improvement and 13 (12.3%) no change, while the results for the 56 cases of low-tone hearing loss were 32 (57.1%), 1 (1.8%), 16 (28.6%) and 7 (12.5%), respectively. Of all patients, 37 had onset of vertigo within 2 to 24 months after steroid therapy, and 17 patients, including 4 with horizontal type, 2 with deaf type and 11 with low-tone hearing loss, were diagnosed with Meniere's disease. The final hearing gain for 4 cases of horizontal type and 2 cases of deaf type sudden deafness was very great. The 17 patients diagnosed with Meniere's disease had hydrops of the inner ear. PMID- 1927457 TI - Eye movement induced by lateral tilt and its clinical significance. AB - We have studied ocular reflexes caused by tilting stimulations in test subjects placed in an upright sitting position on a chair apparatus which tilts continuously. In healthy persons, a weak nystagmus can be observed of minor amplitude and showing a small number of beats. The actual incidence of nystagmus in the younger group was minimal, but it tended to increase with age. This occurrence is considered to be due to age-related degeneration of the otolithic organ. Patients with vertigo and/or dizziness clearly develop nystagmus. These responses are classified as follows: type I is of fixed direction: type II is of changed direction; and type III is a combination of the first and second types. Among the peripheral vestibular disorders, particularly involving patients with benign paroxysmal positional vertigo, a nystagmus of changed direction was found. This type was rarely seen in patients with other vestibular disorders, but was a common occurrence in healthy individuals who readily experienced motion sickness. These observations have led us to conclude that patients with benign paroxysmal positional vertigo have definite reactions which are similar to those of individuals with motion sickness, and that this depends on the susceptibility of the otolithic organs. PMID- 1927458 TI - Neurologic and ENT approach to vertigo. PMID- 1927459 TI - Oculomotor and vestibular findings in developmental dyslexia. PMID- 1927460 TI - Neuro-otological manifestations in different stages of HIV infection. AB - A systematic investigation of the incidence and type of peripheral and central auditory and vestibular disorders occurring in different stages of HIV infection was performed: 43 HIV-seropositive patients (14 were symptomatic with manifestation of AIDS or related complex and 29 were clinically asymptomatic) were compared with a matched control group of 33 HIV-seronegative homosexual volunteers. Among the symptomatic patients 8 (57%) out of 14 and among the asymptomatic HIV-positive patients, 13 (45%) out of 29 had abnormal results in various audiological, vestibular and electrophysiological tests. Only minor anomalies were found in 4 (12%) of the 33 seronegative homosexuals. Our results indicate a high incidence of neuro-otological disorders among patients suffering from AIDS. The numerous electrophysiological abnormalities found in asymptomatic HIV-seropositive persons suggest furthermore an early subclinical involvement of the auditory and vestibular systems. PMID- 1927461 TI - Visual suppression test in patients with spinocerebellar degeneration. PMID- 1927462 TI - Vestibular perceptual deficits in patients with parietal lobe lesions. A preliminary study. PMID- 1927463 TI - Electronystagmographic recordings of guinea pig animal models in experimental otology. AB - The vestibular function test in the guinea pig consists of spontaneous nystagmus recording, positional test and caloric test. If clip electrodes are used, recording of nystagmus in the guinea pig is successful. It takes less than 30 min to complete the whole test, and the animal tolerates the procedure without any complication. PMID- 1927464 TI - Results of damped-rotation tests in brain damaged infants and children. AB - We studied the relation between vestibular functions and neurological diagnosis in 477 brain damaged infants and children who had delayed gross motor functions. They were divided into two groups. Group 1 consisted of 319 infants with cerebral palsy in the first year of life, and Group 2 consisted of 158 brain damaged children up to 4 years of age. The damped-rotation test was used to evaluate vestibular function and the number of perrotatory nystagmus were measured. In Group 1 there were 24 infants with no vestibular responses, including two who were deaf. Five of those in Group 1 showed no responses at the first year of life but normal responses as they developed. In Group 2, all had normal vestibular responses. These results show that the incidence of no vestibular response is very high in infants with spastic cerebral palsy. PMID- 1927465 TI - The vestibulo-autonomic function viewed from cardiac responses in centrifuged monkeys. AB - Vestibulo-autonomic function was examined as the change of cardiac parameters (HR and SV) to +Gz and -Gx accelerations for 1,000 s in intact and bilaterally labyrinthectomized monkeys. Under anesthetized conditions, HR and SV slightly changed to +2Gz acceleration in both monkeys. In +3Gz acceleration, changes were remarkable and significant. HR increased in intact monkeys by as much as 30% while it decreased in labyrinthectomized monkeys, although a moderate initial increase was observed. SV decreased in intact as well as labyrinthectomized monkeys, but the reduction was significant and larger for the latter. This implies that vestibular input could modulate autonomic function. For larger +Gz, both intact and labyrinthectomized monkeys could tolerate no more due to severe cardiac dysfunction (rapid HR and SV decrease) which appeared soon after +4Gz application. In case of -Gx application, HR increased, although slightly, in proportion to the amplitude of applied -Gx in both monkeys, with less changes in labyrinthectomized ones. SV hardly changed in smaller -Gx, while it increased in larger -Gx. Difference between intact and labyrinthectomized monkeys was observed in -6Gx and -8Gx conditions. PMID- 1927466 TI - Therapeutical clinical models using the lower body negative pressure chamber for simulating vertebro-basilar insufficiency syndromes in humans. PMID- 1927467 TI - Centric and eccentric VOR tests in patients with Meniere's disease and vestibular Meniere's disease. AB - Pendular rotation in the eccentric position produces the same angular stimulation as that in conventional pendular rotation and, in addition, involves linear centrifugal and tangential acceleration forces which act on the otolith organs. In the eccentric position, normal subjects showed an increase in gain at 0.64 Hz, when compared with the gain with the head in the centered position. Therefore, we concluded that it is possible to diagnose otolith dysfunction by this comparison. In this study, we applied centric and eccentric pendular rotation tests to patients with Meniere's disease and vestibular Meniere's disease and investigated their otolith function. Patients with Meniere's disease or vestibular Meniere's disease within 1 month after the first attack or the most recent attack showed no gain enhancement with eccentric rotation. However, others showed gain enhancement with eccentric rotation. Therefore, we concluded that there seems to be no difference in the otolith function, especially in utricular function between Meniere's disease and vestibular Meniere's disease. PMID- 1927468 TI - Otoneurological findings in inner ear syphilis. AB - Eighty-one ears in 48 patients who had had ear syphilis for the past ten years were studied and otoneurological examinations reviewed. Twenty-five of 48 cases complained of vertigo, 13 of giddiness and/or unsteadiness, and 10 cases denied dizziness. Approximately one half of the patients had abnormal findings on primary equilibrium examinations, such as Mann's test and stepping test. Spontaneous nystagmus and positional nystagmus were frequently seen on electronystagmographic examinations. Many patients showed abnormal responses to the bithermal caloric test and pendular rotation (VOR) test. Moreover, 5 of 8 patients had positive furosemide VOR tests. On transtympanic electrocochleography, 13 of 22 ears demonstrated a dominant -SP response. Eleven of 26 ears had positive findings on an intravenously administered glycerol test. In conclusion, some cases of inner ear syphilis show the characteristic findings of endolymphatic hydrops. PMID- 1927469 TI - Optokinetic response and adaptation of the vestibulo-ocular reflex (VOR) in a patient with chronic cortical blindness. AB - Optokinetic response and adaptation of the VOR were investigated in a patient with chronic cortical blindness. Our results suggest that: 1) optokinetic response was present in a patient with cortical blindness. This optokinetic response may relate to the extrastriate pathways: 2) the occurrence of VOR adaptation was shown in a patient with cortical blindness, which may indicate preservation of the pathways of the visual-vestibular interaction in the brain stem and cerebellum. The result is in agreement with previous reports in experimental animals; 3) less adaptation of the VOR in this patient than in normal adults may relate to a chronic loss of visual feed back. To the best of our knowledge, this is the first report of adaptation of the VOR in a patient with cortical blindness. PMID- 1927471 TI - Strategy for the diagnosis of small acoustic neuromas. AB - Twenty small (extra-meatal size less than 15 mm) acoustic neuromas have been diagnosed since high-resolution (HR) magnetic resonance imaging (MRI) became available in our clinic. Among these tumors, 18 had sensorineural hearing loss and 16 enlarged internal auditory meatus in X-ray photo, but only 8 tumors out of 18 tested showed diminished caloric response. Auditory brainstem responses (ABR) has been believed as the most reliable test for the diagnosis of acoustic neuroma despite several reports of false-negatives. In our series, 4 tumors out of 18 tested had normal ABR. The false-negative rate was 22%, which is much higher than expected. In CT, only 11 tumors were recognized. Although the total number is not large, present results clearly suggest the limits of these examinations. At present, HR-MRI is the most reliable diagnostic method for acoustic neuromas with no false-negative reported; ordinary MRI may have false-negatives. For the effective use of MRI, the results of audiometry, X-ray photo, ABR and other examinations must be evaluated properly. PMID- 1927470 TI - Visually induced eye movements in Wallenberg's syndrome. AB - Eighteen patients with Wallenberg's syndrome were investigated concerning visually induced eye movements. All results were analysed quantitatively using a computer. In 16 out of 18 patients, OKN slow-phase velocities were impaired, in the remaining 2 patients they were normal. Patients who showed impaired OKN were classified into two groups according to directional asymmetry of OKN impairment. In 7 out of the 16 patients, slow-phases toward the lesion side were predominantly impaired in contrast to the slow-phases toward the intact side (group A). In the remaining 9 patients, slow-phases toward the intact side were predominantly impaired (group B). The smooth pursuit showed the same asymmetry as the OKN slow-phase, except, in 4 patients who showed normal smooth pursuit. All patients showed reduced visual suppression of caloric nystagmus during the slow phase of nystagmus toward the lesion side, except 3 patients who showed normal visual suppression in both directions. CT scan failed to detect either the brainstem or the cerebellar lesions in any cases, but MRI performed on the most recent cases demonstrated the infarctions clearly. These findings suggest that infarctions are localized in the medulla in the patients of group A, but extend to the cerebellum as well as to the medulla in patients of group B. PMID- 1927472 TI - Stepping test evaluated by posturography in vestibular pathology. PMID- 1927473 TI - Postural stability on moving platform oscillating at high frequencies. Effect of vestibular lesion. AB - The effect of linear perturbation at a frequency range of 8 to 24 Hz on postural stability was studied in 7 patients with unilateral vestibular function loss. Force platform technique was used with automatic analysis resulting in the sway velocity of the center point of force. In all patients the support surface movement produced increased sway velocity which was significantly greater than in the controls. Tests at lower frequencies (8 and 10 Hz) produced higher sway velocities than tests at higher frequencies (12, 14, 16 and 24 Hz). The results indicate that the vestibular system controls postural reflexes at a substantially higher frequency range than hitherto suggested. PMID- 1927474 TI - Effect of alcohol measured by dynamic posturography. AB - Thirteen healthy male volunteers aged 21-42 years (mean 27 years) were assessed by dynamic posturography before and after ingestion of alcohol. Each subject was given 0.6 g alcohol per kg body weight in fruit juice to be drunk within 10 min. Alcohol levels in blood samples at 15, 45 and 75 min after ingestion were assessed by gas chromatography. Posturographic measurements were conducted at 30 and 60 min after alcohol administration. Dynamic posturography comprises a sensory organization part in which the support surface and visual surround are either stable or referenced to the patient's sway and the test conditions are eyes open or eyes closed. In a movement coordination part the platform makes active movements. Alcohol levels were 0.40% (SD 0.14) after 45 min and 0.51% (SD 0.14) at 75 min. All subjects presented positional alcohol nystagmus and gaze nystagmus after 45 min. In the sensory organization part of the dynamic posturography in test conditions with eyes closed and the head in neutral position, both with stable (p less than 0.039) and sway-referenced platform (p less than 0.017), alcohol effects were found. In the test condition with sway referenced platform and stable visual surround the effect of alcohol was close to significance (p less than 0.069). When the head was tilted to either side, no effect of alcohol was detected, nor in the movement coordination test. It is concluded that dynamic posturography can detect the effect of alcohol on static and dynamic equilibrium. Test conditions with absent vision appear to be the most sensitive. The results in static conditions are well in agreement with previous studies; the findings under dynamic conditions are new. PMID- 1927475 TI - Galvanically induced body sway in the anterior-posterior plane. PMID- 1927476 TI - Lateral posture stability during galvanic stimulation. PMID- 1927477 TI - Repeatability and effect of instruction of body sway. AB - The effect of instruction and repeatability of posturography measurement was studied in 24 healthy volunteers. In an instruction, "stable" (inverted pendular model) and "relaxed" (segmental oscillating model) positions were studied. In addition, the effect of habituation adaptation, and day-to-day variation were investigated. Sway velocity and average and maximum displacement during vibration perturbated stance were analysed. In individual responses, no statistically significant day-to-day variation could be observed and the individual variation was small. In the "relaxed" condition, the instability was greater when maximum displacement was analysed. No significant changes in sway velocity and average displacement were observed. The results demonstrated remarkable stability of normal postural control mechanism. PMID- 1927479 TI - The Tullio phenomenon in patients with Meniere's disease as revealed with posturography. AB - The effect of low frequency sound (LFS) on postural stability was studied in 55 healthy volunteers and in 50 patients with Meniere's disease. The sound levels ranged from 130 to 132 dB and were given at frequencies of 25, 50 and 63 Hz. The patients with Meniere's disease displayed increased body sway during stimulation. In the individual response, 26% of the patients with Meniere's disease experienced significant body sway. The results demonstrate that subjects with Meniere's disease are sensitive to low frequency sound. The activation of vestibulo-spinal responses by low frequency sound seems to be a result of the Tullio phenomenon, in which sound energy activates the vestibular end-organ. PMID- 1927478 TI - Test for otolith organs with barbecue rotation. AB - In the sitting position, vertical axis head rotation stimulates only the horizontal canal. In the supine position, horizontal axis rotation, so-called barbecue rotation, is a stimulus to both the horizontal canal and otolith organs. We compared dynamic otolith response to these two types of harmonic rotations in 15 normal subjects. The subjects' heads were rotated, passively with eyes open but covered, at the following frequencies: 0.17, 0.33, 0.50, 0.67 and 1.00 Hz. Head movement and eye movement were recorded by scleral search coil technique. Compensatory eye movements were present on each record. Vestibulo-ocular reflex (VOR) gain was calculated using peak-to-peak velocity of the eye and head. At all frequencies the VOR gain of horizontal axis rotation was larger than that of vertical axis rotation. This difference was maximal at the lowest frequency, 0.17 Hz, suggesting that dynamic otolith stimulus improves VOR at low frequencies. PMID- 1927480 TI - Specificity and sensitivity of dynamic posturography. A retrospective analysis. PMID- 1927481 TI - Dynamic posturography in cervical vertigo. AB - Cervical vertigo, the entity of neck disorder and associated vestibular symptoms, was investigated in 15 suspected subjects and results were compared with 15 age matched controls. A modified dynamic posturography investigation with different head positions was used. Head position was recorded 3-dimensionally with electrogoniometry. Differences on a sway-referenced forceplate were found. PMID- 1927482 TI - Postural control in blinds and in Usher's syndrome. AB - The postural control mechanisms were evaluated in 10 blinds and in 10 subjects with Usher's syndrome. The results were compared with 27 age matched healthy volunteers. In visual conditions the subjects with Usher's syndrome performed worse, but in nonvisual condition they performed equally well as the controls. The results were the same irrespective of whether the tests were performed on a rigid surface or foam rubber covered surface. The blinds and controls performed equally well on the bare surface, but the blinds performed significantly better on the foam rubber covered surface. The results indicate that in subjects with Usher's syndrome the vestibulo-cochlear degeneration is well compensated but the postural stability aggravated due to retinal degeneration. Blind subjects have a better postural control than their seeing referents, but the difference is only evident in situations in which the postural control is hampered by surface perturbation. PMID- 1927483 TI - Delayed onset of ototoxic effects of gentamicin in treatment of Meniere's disease. PMID- 1927484 TI - Intratympanic gentamicin therapy for Meniere's disease placed by a tubal catheter with systematic isosorbide. AB - In 1974 (6), 6 patients with incapacitating unilateral Meniere's disease were given an empiric treatment with intratympanic gentamicin sulfate via the eustachian tube using a catheter with a small side-branch. These patients showed excellent results, gaining relief from vertigo over a 13-year period. Since 1980 (7. 8), we have treated patients suffering from Meniere's disease with isosorbide. When the patients could not be controlled by this therapy, isosorbide was given in addition to intratympanic gentamicin therapy using a tubal catheter. Of 75 patients with Meniere's disease who received gentamicin and isosorbide therapy, 41 could be evaluated by the classification of the American Academy of Opthalmology and Otolaryngology (AAOO) in 1987 (9). Three of these patients suffered from repeated attacks of vertigo for 2 years. However, all of them could be easily controlled by additional intratympanic gentamicin or isosorbide therapy on an out-patient basis. Thereafter, of a further 40 patients with incapacitating Meniere's disease who received gentamicin and isosorbide therapy, 15 could be evaluated by the AAOO classification. In summary, of the 115 patients with incapacitating Meniere's disease treated with intratympanic gentamicin after isosorbide treatment, 56 could be evaluated by the AAOO criteria from 1987 to 1990. These patients ranged in age from 21 to 79 years. Vertigo improved in 80% of the patients: 19 patients (34%) were group A. 22 patients (39%) were group B, 4 patients 7%) were group C and 11 patients (20%) were group D, of whom 9 patients required subsequent endolymphatic-mastoid shunt operations. This treatment also effectively controlled patients with bilateral Meniere's disease. PMID- 1927485 TI - Treatment of vestibular disorders. AB - At our department, we generally perform inner ear anesthesia with lidocaine and intratympanic dexamethasone injection for treatment of patients with Meniere's disease or labyrinthine vertigo due to circulatory disturbances of the inner ear, having failed other conservative treatments. These treatments were performed in 322 patients who consulted us during the past 7 years, including 136 patients with Meniere's disease and 186 patients with labyrinthine vertigo. The criteria for evaluation of the therapeutic effect included the AAOO (1972), the AAO-HNS (1985) and Sakata's (1987) method. Both therapeutic methods were effective not only for the inhibition of vertiginous attacks, but also for the treatment of tinnitus. In the overall evaluation of therapeutic effect, dexamethasone injection was more effective than inner ear anesthesia in cases of Meniere's disease whereas inner ear anesthesia was more effective than dexamethasone injection in cases of labyrinthine vertigo. When the three methods of evaluation were compared, the rate of positive effect increased in this order: the AAOO method showed fewer positive effects than the AAO-HNS method, and fewer than or equal to Sakata's method. For example in cases of Meniere's disease that are resistant to drug therapy, these two therapeutic methods appear to be worthwhile before attempting surgical treatment for refractory vertigo. PMID- 1927486 TI - Physical treatment of benign paroxysmal positional vertigo. PMID- 1927487 TI - Effect of yunfujing on the vestibular system. AB - Yunfujing is a traditional chinese drug which in earlier studies has been shown to reduce vestibular signs in man on a rotatory chair with coriolis accelerate stimulation. Recently 131 patients were studied including all kinds of peripheral vestibular disturbances. Eighty-nine cases were treated with yunfujing and 42 controls were given armillaria mellea vabi which has the same effect as diphenidol. We found that yunfujing has the same effect as armillaria mellea vabi or diphenidol: the symptoms were reduced in a few days. PMID- 1927488 TI - Influence of gravity vector on eye movement elicited by linear acceleration. AB - When the body/head motion is sensed by otolith organs, they respond not only to the resultant acceleration of the motion but also to the gravitational force. We investigated the influence of the gravity vector on the otolithic-ocular reflex caused by motion in normal subjects. The sled type linear accelerator, moving back and forth with a frequency of 0.25 Hz and an amplitude of 2 m, generated right-left linear acceleration with a maximum magnitude of 0.5 g. We tested every subject under seven different postures: 1) 135 degrees forward tilted (F.T.), 2) 90 degrees F.T., 3) 45 degrees F.T., 4) upright sitting, 5) 45 degrees backward tilted (B.T.), 6) 90 degrees B.T., and 7) 135 degrees B.T. Horizontal eye movements with nystagmic pattern were elicited by these stimulations and were recorded by EOG. The eye movement data were analyzed by using a computer with the following procedure. After extraction of saccadic components from the data, the remaining parts were connected smoothly. The waves reconstructed in this manner, considered to be primary otolithic-ocular responses, were processed with the FFT method for calculating the amplitude of the component at 0.25 Hz. As a result, the responses were larger in the forward tilted postures than in the backward tilted postures. PMID- 1927489 TI - Sinusoidal linear accelerations test on peripheral vestibular disturbances. PMID- 1927490 TI - Cortical projections of otolith organs in the cat. PMID- 1927491 TI - The mechanism of irritative nystagmus and paralytic nystagmus. A histochemical study of the guinea pig's vestibular organ and an autoradiographic study of the vestibular nuclei. AB - To establish the difference of mechanism between irritative and paralytic nystagmus, alterations of Na-K-ATPase and succinic dehydrogenase activity in the vestibular sensorineural elements were investigated for 20 guinea pigs, and glucose uptake of the vestibular nuclei for 13 guinea pigs were measured by the [14C]-2-deoxy-D-glucose method. Irritative and paralytic nystagmus were experimentally provoked by introducing K+ into the perilymphatic space. From the results it was concluded that irritative nystagmus is provoked by increased excitability of vestibular sensory cells, while paralytic nystagmus is provoked by decreased excitability. However, the direction of nystagmus was eventually decided by the tonus imbalance between the bilateral vestibular nuclei. The ipsilateral vestibular nucleus was predominant during irritative nystagmus, while the contralateral vestibular nucleus was predominant during paralytic nystagmus. PMID- 1927492 TI - Effect of gentamicin intoxication on frog behavior. AB - Eighty micrograms of Gentamicin were injected into bull frogs' perilymphatic cistern for 3 days. Behavioral changes were evaluated together with morphology of the semicircular canal crista and the utricular macula. The behaviors evaluated were posture, walking, head stability, jumping and swimming. The earliest change of behavior was noticed one day after the last injection, and the changes tended to develop over the following 1 to 2 weeks. When the utricular macula was damaged, the frog tilted toward the damaged side. No tilting was observed when bilateral utricles were intact, or when bilateral utricles were equally damaged. Damage of the posterior (p.v.c.) and anterior vertical canal (a.v.c.) cristae resulted in instability of the head. Jumping ability also deteriorated when the p.v.c. and a.v.c. were damaged. These results indicate that p.v.c. and a.v.c. are involved in head stability and jumping function, while the utricle contributes to perception of gravity. PMID- 1927493 TI - Mechanical properties of membranous labyrinths measured with a microtension tester. AB - Mechanical properties of the semicircular canals of guinea pigs, frogs and water fishes, and of human membranous labyrinths were tested. Tensile strength of the semicircular canals of guinea pig, frog and water fish was greater in the order of guinea pig, frog and fish. In the human membranous labyrinth, the saccular membrane was the weakest, followed by Reissner's membrane, the utricular membrane and the semicircular canal. These values were converted from tensile strength to breakage pressure. The breakage pressure of the saccular membrane was 64.0 mmHg. PMID- 1927494 TI - The effect of furosemide on the endocochlear potential in ears with experimentally induced endolymphatic hydrops. AB - The endocochlear potential (EP) was measured in 38 guinea pigs with experimentally induced endolymphatic hydrops at the 3rd, 6th, 12th and 24th postoperative weeks, and the effects of furosemide (FUR, 50 or 80 mg/kg) on the EP were examined. A time-related reduction of the EP from the normal value and increased susceptibility to FUR were disclosed in the hydropic animals. Furthermore, 24-week animals given 80 mg/kg FUR showed a significantly slower recovery rate of the EP than the other groups, indicating impairment of the strial function progressive with post-operative time. The negative component of the EP was considered to be unimpaired until at least 12 weeks after the surgery. PMID- 1927495 TI - Computed tomographic findings around the vestibular aqueduct in Meniere's disease. AB - High resolution transverse axial CT encompassing the lateral semicircular canal was used to study the visualization of the vestibular aqueduct and to measure the minimum distance between the posterior semicircular canal and the posterior petrous surface (P-P distance) in Meniere's disease and chronic otitis media. The results indicate that the development of the bone between the posterior semicircular canal and the posterior petrous surface, which usually contains the endolymphatic sac, is significantly poorer in affected ears than in nonaffected ears in unilateral Meniere's disease, and much poorer than in chronic otitis media. PMID- 1927496 TI - Canal-plugging in the rhesus monkey. A tool to study the contribution of individual canals to nystagmus generation. PMID- 1927497 TI - Mechanisms of caloric stimulation of the pigeon's vestibular system. PMID- 1927498 TI - Histological changes of vestibular nerves and ganglion cells in the acoustic tumor in relation to clinical functions. AB - The superior vestibular nerves and vestibular ganglion cells were observed electron microscopically in acoustic tumors removed surgically from 15 patients. Furthermore, the sensory cells of the vestibular organs were examined. Histological changes of vestibular nerves and ganglion cells were compared with the caloric responses of the patients. In most cases, the degree of degeneration of myelinated nerve fibers was proportional to the reduced responses of vestibular nerves. The myelinated nerve fibers decreased in number and showed some features of demyelination. The alteration of vestibular ganglion cells was unremarkable in comparison with vestibular nerves. In some cases, the number of lipofuscin granules, vacuolar organelles and amorphous materials markedly increased in the ganglion cells. However, the sensory cells of the vestibular organs appeared normal. PMID- 1927499 TI - [Carcinoma of the larynx. Recent diagnostic, therapeutic and rehabilitation findings]. PMID- 1927500 TI - [Reconstruction of the cervico-cephalic region with combined myocutaneous flaps]. PMID- 1927501 TI - [Tracheoesophageal fistula]. PMID- 1927502 TI - [Indications and advantages of vocal rehabilitation of laryngectomized patients using tracheoesophageal prosthesis]. PMID- 1927503 TI - [Endoscopy in the diagnosis and staging of cancer of the larynx]. PMID- 1927505 TI - [Partial vertical laryngectomy (anterior frontal laryngectomy, fronto-lateral laryngectomy). Indications and long-term results]. PMID- 1927504 TI - [Supraglottic horizontal laryngectomy]. PMID- 1927506 TI - [Hemilaryngectomy and reconstructive laryngectomy]. PMID- 1927507 TI - [Treatment of No lymph nodes in laryngeal tumors, stages I and II]. PMID- 1927508 TI - [Total laryngectomy: techniques, oncological results, complications]. PMID- 1927509 TI - [Surgery of lymph nodes N1-N3: conservative or radical dissection]. PMID- 1927510 TI - [Laryngeal precancerous conditions]. PMID- 1927511 TI - [Radiotherapy of primary tumors and lymph nodes N1-N3]. PMID- 1927512 TI - [Surgery of lymph nodes after irradiation]. PMID- 1927513 TI - [Obstruction treatment using lasers in laryngotracheal neoformations]. PMID- 1927514 TI - [Radical surgery: laryngo-pharyngectomy in advanced cases]. PMID- 1927515 TI - 10th International Symposium on Growth and Growth Disorders. Proceedings of a meeting. Madrid, Spain, 19-20 October 1990. PMID- 1927516 TI - Development of anti-hGH antibodies during therapy with authentic human growth hormone. AB - Children treated with authentic human growth hormone (Genotropin) in clinical trials between 1985 and 1989 were tested for the presence of anti-hGH antibodies. The incidence of antibodies after 12 months of treatment was 4/373 (1.1%). Mean binding capacity was 0.07 mg/l. The results suggest that Genotropin has low immunogenicity. PMID- 1927517 TI - Gonadotrophin and growth hormone secretion throughout puberty. AB - The secretion patterns of gonadotrophin and growth hormone (GH) were investigated in normal healthy children at different stages of pubertal development. The plasma levels of luteinizing hormone (LH) and GH were measured at 10-minute intervals from 12.00 h to 18.00 h and from 24.00 h to 06.00 h using immunoradiometric assays. The levels of follicle-stimulating hormone (FSH) and testosterone were measured hourly. In young prepubertal girls and boys LH was undetectable during the day or night. In children of pubertal chronological age, in whom secondary sexual characteristics had not appeared (stage 1 onset), LH was detectable during the night only. With the progression of puberty there was a gradual increase in the secretion of LH, resulting from increases in both the frequency and amplitude of LH pulses. There was a clear increase in the secretion of FSH during day and night from stage 2 onwards. The secretion of GH also increased with the progression of puberty, due to an increase in pulse amplitude. The increase in GH secretion did not appear to be related to the increase in LH secretion, but rather to changes in the sex steroids. PMID- 1927518 TI - Gonadotrophin-releasing hormone analogues as therapeutic probes in human growth and development: evidence from children with central precocious puberty. AB - Statural growth and skeletal development were assessed in 87 girls with idiopathic central precocious puberty (CPP) during gonadotrophin-releasing hormone analogue (GnRHa)-induced suppression of gonadarche. Before the start of therapy, mean chronological age (CA) was 6.3 years and mean bone age (BA) was 10.6 years. During up to 6 consecutive years of complete suppression of gonadal sex steroid secretion, the mean height velocity decreased from 10.8 cm/year to prepubertal rates. At each interval height velocity was found to be inversely and negatively correlated with BA such that girls with advanced BAs grew at rates well below prepubertal norms but appropriately for their degree of skeletal maturation. Skeletal maturation similarly slowed during prolonged GnRHa administration (delta BA/delta CA = 0.6 +/- 0.1 over 3 years, mean +/- SD, n = 66) and was also negatively correlated with the BA before the start of therapy. Predicted adult height increased progressively during therapy; however, when analysed as changes in height SDS(BA), the impact of treatment was variable and correlated positively with the initial degree of skeletal maturation. The effect of GnRHa therapy on growth in children with CPP requires long-term study and is best analysed by employing a developmental perspective. PMID- 1927520 TI - Conversion of diurnal plasma hormone concentration profiles into secretion rates. AB - Various methods for the calculation of hormone secretion rates from plasma hormone concentration time-series are described. Problems related to the description of the basic processes of hormone kinetics, including secretory pulsatility, distribution, and elimination are discussed, as well as methods for the experimental validation of models. Computer modeling and simulation techniques are shown to be very useful in this respect. It is suggested that more sophisticated biophysical models are developed to describe hormone dynamics more accurately, for example, with regard to kinetically different molecular forms of the same hormone, and to the interaction of hormones with hormone-binding proteins. Such models would provide the basis for more accurate estimation of hormone secretion rates. PMID- 1927519 TI - Management of growth hormone deficiency through puberty. AB - As a model of the growth hormone (GH) dependence of growth in prepuberty and puberty, the growth of 182 children (93 boys, 89 girls) who survived in first remission for treatment of acute lymphoblastic leukaemia was examined. Chemotherapy regimens, including intrathecal methotrexate, were similar in all patients, but CNS treatment differed, in that one group received 2400 cGy cranial irradiation, while the other received 1800 cGy. There was a significant decrease in height SDS during prepuberty, which was equivalent in both sexes, whereas there was a much greater decrease in pubertal growth in girls than in boys. Girls treated with the lower dose regimen of cranial irradiation had their onset of pubertal maturation significantly advanced, to a mean of 9.9 years (p less than 0.001). Previous studies have indicated that the duration of puberty is shortened by GH treatment in patients with idiopathic multiple pituitary hormone deficiency or isolated GH deficiency (GHD). To determine whether an increase in the dose of GH administered during the adolescent growth spurt would improve final height, a prospective randomized trial was performed in 32 children (25 boys, 7 girls) with isolated GHD treated with a GH dose regimen of 15 IU/m2/week as daily s.c. injections. At the onset of the pubertal growth spurt, the patients were randomized either to an unchanged dose or to 30 IU/m2/week. There was no significant change in height velocity with the doubled dose of GH, but there was a trend in the advancement of pubertal maturation which was considered to be dose related. It is suggested that these findings are of relevance to the treatment of GHD in puberty, especially in girls with early or precocious puberty occurring as a consequence of low-dose cranial irradiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927521 TI - Synchronization of hormonal time series: analytical approaches. AB - Comparison of the patterns of episodic secretion of two or more hormones measured simultaneously often suggests that peak levels tend to occur at around the same time. This visual impression can be misleading, however, as some peaks will occur simultaneously due to chance alone. Traditional cross-correlation methods are suitable for evaluating linkages among circadian and other smoothly varying rhythms, but are less well suited to correlating ultradian peaks. This paper proposes a method which entails identifying peaks of hormone secretion as discrete events in several different series, and counting the frequency of simultaneous and near-simultaneous peaks in temporal 'windows' of increasing width. The expected rates of random coincidences can be assessed by a variety of methods, including simulations and probability calculations. The method described utilizes simple techniques which make few assumptions about the character or stationarity of the series, comparing coincidence rates in the appropriately paired series with those in which a series in one subject is deliberately 'mismatched' with that of another subject. Using this approach, a significant excess of simultaneous peaks of luteinizing hormone (LH) and prolactin was found in normal subjects as compared with mismatched series (17% versus 6%; p less than 0.05). Hypogonadotrophic men treated with pulsatile gonadotrophin-releasing hormone (GnRH) have an even higher coincidence rate (26%). By contrast, the rate of coincidence between pulses of LH and cortisol is not significantly greater than that which would be expected due to chance. PMID- 1927522 TI - Molecular biology of the insulin-like growth factors: gene structure and expression. PMID- 1927523 TI - Paracrine and autocrine regulation of insulin-like growth factor I. PMID- 1927524 TI - The endocrine role of insulin-like growth factor I. PMID- 1927525 TI - Dietary allowances: what to recommend. AB - Within recent years Recommended Dietary Allowances (RDAs) have come to play a major role in a wide range of governmental, health and industrial affairs. Each of these applications, however, sets different specific requirements. All too frequently the basic RDA values end up by becoming processed in ways which exceed the limits of the science on which the recommendations were formulated. Currently, the same sets of RDAs are being applied to functions as varied as food labelling, public health assessments of populations, agricultural planning, the organisation of diets for institutional feeding and the diagnosis of under nutrition or malnutrition. In order that these actions can be carried out effectively and meaningfully, a knowledge of how RDAs are derived and expressed is essential. PMID- 1927526 TI - Energy requirements of pregnancy. AB - The energy requirements of pregnancy is a topic of considerable uncertainty because the apparent energy costs--to supply the energy required for the changes in maternal and fetal tissues and to cover the increase in BMR (basal metabolic rate), amounting to the equivalent of an extra 250-300 kcal/d--are rarely paralleled by actual findings. However few studies have investigated this problem in a controlled, longitudinal, and statistically acceptable fashion. In the present study, measurements of energy intake, BMR, body weight and fatness, physical activity, and mechanical efficiency of movement, were made on 162 women in Scotland at 2 to 4 weekly intervals throughout pregnancy and data from 98 of these women were also obtained in the pre-pregnant state. Data from a parallel study in Holland are also given. The gains in body weight, fatness, the fetal and placental weights, and the increase in BMR were all at the normal expected values. However, increases in energy intake were of the order of only 100 kcal/d during the second and third trimesters. Comparatively small reductions in physical activity, which would be very difficult to measure precisely, are described which could account for the difference between actual energy intakes and the energy costs of pregnancy. PMID- 1927527 TI - Management of inborn errors of metabolism during pregnancy. AB - An increasing number of women with inherited metabolic disorders survive, conceive and have children. In order to safeguard the health of the mother and the developing embryo, fetus, and newborn during pregnancy, delivery, and the neonatal period it is necessary to be aware of the range of metabolic disorders, the risks to mothers and children, and appropriate management strategies. The roles of the Paediatrician, Obstetrician and Dietitian in the management of Maternal Hyperphenylalaninaemia and phenylketonuria are reviewed. PMID- 1927529 TI - Teeth for the future. AB - The main dietary influences on teeth are, with the exception of ingested fluoride, local rather than systemic. The frequent use of carbohydrates which can be rapidly fermented by dental plaque micro-organisms is the major factor in dental decay. Sweetened and/or highly acidic soft drinks or medicines sweetened with sugars may damage the teeth. Similarly infant's comforters also have their dangers if they provide prolonged exposure of the teeth to cariogenic conditions. Although dental caries is primarily a disease of children many adults still develop new lesions and adults who have lost gingival tissue through periodontal disease may develop root surface caries. Pathological conditions of the oral mucosa can arise from nutritional disorders or inappropriate dietary habits. Health education is most effective when it carries a positive message so encouraging patients to eat the right kind of tasty snacks and to round off meals with sugar-free products or a modicum of cheese should in healthier eating without conflicting with general health guidelines. PMID- 1927528 TI - Protein and energy interactions throughout life. Metabolic basis and nutritional implications. AB - We review selected aspects of the interactions between protein and energy in human metabolism and nutrition. Following a short account of the underlying metabolic basis for the effects of energy on protein metabolism, the contribution made by whole body protein turnover to the metabolic rate is discussed, including the relationship between protein turnover and energy metabolism at different phases of life. The effects of changes in energy metabolism and intake on the nitrogen economy of the host are also reviewed briefly and we explore the relationship between amino acid oxidation and requirements for indispensable amino acids. Interactions between energy and protein metabolism need to be investigated in greater detail and also they must be considered in relation to further attempts to establish more precisely energy and amino acid requirements of people under various circumstances. PMID- 1927530 TI - Bones for the future. AB - In the course of the present century the major metabolic bone problem in the West of Scotland and Northern Europe in general has changed from that of rickets/osteomalacia with its attendant deformity and loss of stature, to osteoporosis and a consequent epidemic of fractures in older people. Advances in understanding the intermediary metabolism of vitamin D have resulted in a better appreciation of the role of air pollution in the rickets pandemic during the latter part of the 19th and early part of the 20th century, but the persistence of the problem in Asian immigrants and in certain special clinical situations had led to a reappraisal of the importance of dietary constituents other than vitamin D itself. Technical advances in the measurement of bone mass have permitted a closer examination of the aetiological factors influencing bone mass and fracture incidence. It seems likely that there is a relationship between increased dietary calcium intake in childhood and adolescence and peak bone mass in the fourth decade, but the definition of "adequate" and "optimum" remains insecure. The most important reason for women becoming at risk of fracture in later life relates to the dramatic reduction in bone mass consequent upon the menopause--a feature which can be arrested by the administration of oestrogen but hardly at all by calcium. The bulk of evidence supports the view that the negative calcium balance found in post menopausal osteoporosis is a consequence rather than a cause, and that dietary calcium can only--if at all--influence the course of events if pushed up to unusually--and for many, intolerably--high levels. Although other life style components such as exercise, alcohol consumption or cigarette smoking may also have a role, the principal impact on reducing the problem of post menopausal fracture is likely to be through the wider acceptance of hormone replacement therapy. PMID- 1927531 TI - Cholesterol: should we screen all children or change the diet of all children. AB - Hypercholesterolaemia is a major risk factor for coronary heart disease and may present during childhood. Dietary measures can reduce plasma cholesterol and may thus delay or prevent the development of the atherosclerotic process. Although plasma cholesterol concentrations measured during childhood track into adult life with a correlation coefficient of about 0.6 this in itself is insufficient to justify total population screening of children especially as the mechanisms for management and follow-up and their social, psychological and economic implications have not been adequately evaluated. Targeted screening of children in families with the genetic disorder of familial hypercholesterolaemia, where the risk of premature coronary heart disease is very high, should, however, be undertaken even though such screening may only identify half of all affected children. Dietary change designed to lower plasma cholesterol can be applied to the whole population including children over the age of 2 years, does not require pre-determination of plasma cholesterol, and is to be recommended. The effects of such change on the growth and health of children should be monitored. PMID- 1927532 TI - Place of birth and adult cardiovascular disease: the British Regional Heart Study. AB - Coronary heart disease (CHD) is almost certainly a nutritional disorder related to the quality and quantity of dietary fats and mediated by blood and tissue lipid concentrations. There is current controversy as to when the underlying process of atherosclerosis is initiated and whether the critical susceptibility to CHD may be established in utero or infancy. Blood pressure and hypertension may also be nutritionally based, and the age at which the rate of rise in blood pressure with age is determined is also controversial. The British Regional Heart Study (BRHS) involves 7,735 middle-aged men from 24 towns in England, Wales and Scotland and reveals that average blood cholesterol levels in these towns show no relationship to CHD mortality but all are high by international standards. Blood pressure levels vary markedly between the 24 towns and relate strongly to CHD mortality patterns, which are highest in Scotland and lowest in the South of England. The hypothesis relating adult blood pressures and CHD mortality to foetal and infant life circumstances has been examined using the data on birthplace and place of examination of the BRHS men. Regardless of where they were born, men living and examined in the South had lower mean blood pressures than men living in Scotland. The highest mean blood pressures were observed in Scotland, irrespective of where the men had been born. For CHD, regardless of their place of birth, men living in the South had a lower risk of CHD than men living elsewhere. The geographic zone of examination appeared to be more important than the zone of birth in determining the risk of CHD and the level of blood pressure. While patterns of nutrition during pregnancy, in infancy and childhood may be of importance for some outcomes, such as height, it seems that exposure to risk factors during adult life predominantly determine the outcome in cardiovascular disease. PMID- 1927533 TI - Target weight in children and adolescents with anorexia nervosa. AB - Establishing realistic weight goals and their effective use in treatment is an integral part of management in anorexia nervosa. However, the processes involved are discussed rarely in the clinical and research literature. Various methods for setting target weights are reviewed, with consideration of the relative merits of their application in the treatment of pre-pubertal children and adolescents with anorexia nervosa. PMID- 1927534 TI - The nutritional consequences of gastrointestinal disease in adolescence. AB - The growth spurt of adolescence, during which body weight nearly doubles and height increases by 16%, demands an increased delivery of nutrients by the gastrointestinal tract. Chronic disorders of digestion and absorption at this age, therefore have a potentially profound effect upon growth, skeletal maturation and sexual development. Moreover, the emotional climate of adolescence, which requires affiliation with peer groups, and a distancing from authority figures such as doctors and parents, is often associated with a deterioration in drug and dietary compliance and with erratic clinic attendance. Nutritional problems in adolescent patients with Crohn's disease, cystic fibrosis and coeliac disease are the most common. About one third of adolescents with Crohn's disease experience growth failure and delayed sexual development, probably as a consequence of long-term undernutrition. There is a strong argument for the care of these patients being in the hands of paediatric gastroenterologists. Enteral nutrition, often administered overnight, is successful in inducing catch-up growth, and reducing steroid dosage, although resection of diseased gut is often followed by good growth, and surgery should not be overlooked. Cystic fibrosis in adolescence is commonly complicated by protein-energy malnutrition. Pathogenesis includes anorexia, maldigestion and an increase in resting energy expenditure. Malnutrition has been treated by a number of enteral regimens. In general, there is no place for repeated, short-term interventions of less than 6 months. Long-term studies have all shown good nutritional repletion and growth, but results with respect to improved respiratory function are conflicting. More prospective control trials are needed before the precise indications for enteral nutrition in cystic fibrosis can be accurately defined. Once started it is difficult to stop, although preoperative treatment of patients awaiting heart-lung transplantation seems entirely appropriate. The major problem in the management of coeliac disease in adolescence is dietary compliance. Even those patients who claim to have good dietary compliance often have jejunal biopsy evidence of gluten ingestion and tend to be underweight. This is particularly worrying, as after 5 years adherence to a gluten free diet, the increased risk of gastrointestinal malignancy appears to return to normal. PMID- 1927535 TI - Temporary changes of protein level in liver after AET or MEA treatment prior to 60Co gamma-irradiation of male mice. AB - The adult male Swiss mice were either whole-body gamma-irradiated with a single dose of 10 Gy from 60Co source, always at 19.00 or, 15 minutes before irradiation injected intraperitoneally with AET (2-aminoethylisothiouronium Br. HBr), or MEA (cysteamine HCl), in a dose of 400 mg/kg body weight. The measurements of the protein level in crude homogenates of liver were done in four-hour internals during a 24-hour period, starting at 20.00. The protein concentration in liver was calculated per 1 g of fresh tissue and the whole organ weight. The body and liver weight was also studied. There were no fluctuations in the liver weight and concentration of protein in the control and irradiated only mice. Temporary changes in the liver weight and level of protein expressed in mg per 1 g of fresh tissue and the whole organ weight could be found in the group of males treated with AET, and daily changes in the liver weight and concentration of protein related to mg per 1 g of fresh tissue, in the group of male mice injected with MEA prior to irradiation, could be recorded. Differences in the liver weight at 20.00, 24.00 and 04.00, as well as in the protein level expressed in mg per 1 g fresh tissue at 04.00, 12.00, 16.00, and the whole liver weight at 24.00, 04.00, and 16.00, of between the particular groups of mice, were observed. There were no temporary changes in the body weight in any of the groups and there were no differences in this value between the groups of mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927536 TI - Estimation of the optimal tissue oxygenation parameters in adult respiratory distress syndrome (ARDS). AB - We hypothesised earlier that the simultaneous examination of the basic tissue oxygenation parameters (O2 delivery-DO2, O2 extraction ratio-O2ER, O2 consumption VO2) results in a more adequate relationship to characterize the oxidative metabolism of tissues than a separate evaluation. The aim of present study was to prove this hypothesis. That is for while the results of these oxygenation measurements were examined simultaneously in a 3-dimensional analysis in 30 patients with ARDS. It was found that all measured values distributed on a 3 dimensional space net. An optimal range on the tissue oxygenation surface could be separated where 64% of the data of survivors were inside this range, while 77% of the data of "late stage" nonsurvivors--patients, where the measurement were done on the last 5 days of their life--were outside this range. The therapeutic goal in the treatment of ARDS patients is to change the oxygenation parameters to be inside this optimal range. PMID- 1927537 TI - Analysis of the influence of aeroions on ECG and correlation between this action and tissue redox-state potential. AB - It was observed in rats, that following negative aeroionization heart frequency and the altitude of P-waves increased. After positive ionization these interrelationships took place inversely. As between these effects and the tendency of tissue redox-state potential changes correlation was seen, the results were grouped also on redox basis, independently on whether the increase or decrease of redox-state potential was caused by negative or positive aeroions. The results of this grouping showed, that following an elevation of tissue redox state potential (+delta E'0) heart frequency dropped, and the altitude of T-waves increased. After a decrease of tissue redox-state potential (-delta E'0) these interrelationships were realized inversely. After -delta E'0 the positive chronotropic influence of noradrenaline increased, but consequent to +delta E'0 the classical positive chronotropic effect of this catecholamine was reversed. These results corroborate our earlier notion, that aeroions exert their action on heart through changing tissue redox-state potential. PMID- 1927538 TI - Changes in collagen content of the diaphragm in rats of different ages. AB - Rat diaphragm showed a nine to ten-fold increase in the dry and wet weights and a four-fold increase in its surface area between 21 and 540 days of age. The increase was the most rapid between days 21 and 90, thereafter a non-significant trend of increase was maintained at least up to 360 days of age followed by a tendency to decrease. The total collagen content of the diaphragm paralleled the increase in surface area with progressing age. The collagen content significantly dropped when expressed relative to the dry weight of the diaphragm, between 21 and 90 days of age. This trend was maintained till 180 days of age but thereafter significantly rise was seen. These later changes may be due to elenated synthesis and/or reduced degradation of collagen, and may contribute to the decline in contractility of the diaphragm as age advances. PMID- 1927539 TI - Seasonal variations in the contractile behaviour of gastrocnemius muscles of Uromastix hardwickii. AB - Seasonal variations in the isometric activity of the isolated gastrocnemius muscle of Uromastix hardwickii was studied from winter to summer in Karachi, Pakistan. A constant 20 degrees C temperature was maintained during experimentation to avoid influence of this factor on seasonal changes. The twitch and tetanic tensions recorded at resting lengths showed a significant rise from winter to summer (p less than 0.0005) with a greater effect on tetanic tensions. The rate of rise of tensions also showed a significant elevation (p less than 0.0005) from winter to summer, while the duration of active state decreased by 66% during spring and summer. The results are discussed in terms of speed of summation of active state, cross bridge interaction, and characteristic expression of gastrocnemius muscle morphology on its mechanical behaviour from winter to summer. PMID- 1927540 TI - Influence of 3-methylcholanthrene on the redox-state of liver and red muscles in vivo. AB - It was observed, that following an injection of 3-methylcholanthrene (MC), the tissue redox-state potential is modified expressively both in liver and in red muscles. In the liver in the first day an oxidosis develops, which is followed by redosis, but in the muscle a redosis can be observed already in the first day. It is a meaningful fact, that MC influences biochemical processes in the early phase of its effect not only in the liver but also in the red muscle. By reason of this data the possibility of a prevention of the MC influence by adequate redox agents might also be arised. PMID- 1927541 TI - Relationship between the antitussic and analgesic activity of substances. AB - The authors studied relationship between the antitussic and analgesic activity of substances. The antitussic effect of codeine, tilidine, tramadol and pentazocine has been studied in nonanesthetized healthy cats. The drugs except tilidine, were administered intraperitoneally in a dose of 10 mg/kg body weight. Tilidine was administered intramuscularly in the same dose. Cough induced in nonanesthetized cats by mechanical irritation of laryngopharyngeal and tracheobronchial areas was evaluated by changes of the lateral tracheal pressure. A significant decrease of the subsequent cough parameters was observed after the application of codeine, tilidine, tramadol and pentazocine. Naloxone given 5 min before the application of the drug has not prevented the cough-suppressing effect due to codeine. Naloxone alone administered in a dose of 1 mg/kg body weight has not significantly influenced the experimentally-induced cough reflex in nonanesthetized cats. PMID- 1927542 TI - Cough reflex in rabbits 24-h and 48-h after sulphur dioxide breathing. AB - The cough reflex elicitability (CRE), cough reflex strength (CRS) and Hering Breuer inflation reflex (HBIR) were studied in 51 anaesthetized (Pentobarbital Spofa, 30 mg/kg, i.v.) female rabbits 24-h and 48-h after SO2 breathing. To provoke cough, the interior of the trachea and carina were stroked with a polyethylene catheter. To elicit the HBIR, the lungs were inflated to 1.0 kPa intratracheal pressure. Intrapleural and systemic blood pressures were recorded. The CRE, CRS and HBIR obtained 24-h and 48-h after SO2 breathing were compared with correspondent values of control animals. It was found, that CRE and HBIR were fully recovered 24-h after SO2 breathing, but the CRS was still decreased, however, there were no significant differences in CRE, CRS and HBIR between animals 48-h after SO2 breathing and control animals. It can be concluded, that decrease of the CRS 24-h after SO2 breathing is not due to slowly adapting stretch receptors block of airways. PMID- 1927543 TI - Relationship between exchangeable body sodium and urinary 6-keto-prostaglandin F1 alpha excretion in normal man. AB - The renal prostaglandins are involved in the regulation of sodium balance. In the present study exchangeable body sodium (NaE) and the urinary excretion of the stable metabolite of prostacyclin, 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha) were determined simultaneously in 10 hospitalized healthy individuals. NaE was 1461 +/- 107 mmol/m2 body surface area, or 98.5 +/- 6.9% when expressed as percent of the normal value assessed on the basis of measurements in 54 control subjects. The excretion of 6-k-PGF1 alpha amounted to 68.3 +/- 39.2 ng/4 hr. Statistical evaluation revealed significant correlation between NaE and PGF1 alpha excretion (r = 0.642; p less than 0.05) and between the serum Na concentration and the urinary excretion of 6-k-PGF1 alpha (r = 0.865; p less than 0.001). The obtained results indicate that urinary 6-k-PGF1 alpha excretion, hence the renal synthesis of prostacyclin, are regulated, among other factors, by body sodium stores. The increased production of prostacyclin with expanding sodium space might be regarded as a compensatory response contributing to the renal elimination of excess sodium from the body. The signal to this response could be the serum Na concentration. PMID- 1927544 TI - Effect of immobilization on carbonic anhydrase III and myoglobin content in human leg muscle. AB - Carbonic anhydrase III and myoglobin concentrations were measured from vastus medialis muscle samples before and 6 weeks after postoperative leg immobilization following knee ligament reconstruction. Seven patients were immobilized with conventional cast so that the knee joint was fixed at 20 degrees flexion. Seven other patients used braces allowing a motion of 30-70 degrees. The atrophy of the medial part of musculus quadriceps was estimated by computer tomography. No difference in carbonic anhydrase III and myoglobin concentrations or muscle atrophy between the cast and brace groups was observed. The cross-sectional area of the medial part of musculus quadriceps decreased 38% during immobilization. The specific concentrations of carbonic anhydrase III and myoglobin remained unaltered. Due to the remarkable postoperative atrophy of the muscle the total carbonic anhydrase III and myoglobin contents, however, decreased significantly (37% and 31%, respectively). The results suggest that the net breakdown of carbonic anhydrase III and myoglobin during disuse atrophy occur at the same rate as the average net degradation of mixed muscle proteins and that the process is independent of the immobilization procedure. PMID- 1927545 TI - Pulmonary flow-resistive work during hydrostatic loading. AB - This paper focuses upon flow-resistive pulmonary work during upright immersion, and during changes in the air delivery pressure. Nine male non-smokers (aged 26.2 +/- 3.5 years), with normal lung function history, performed spontaneous respiration while seated in air (control) and during total immersion. During the immersed state subjects were supplied with air at four hydrostatic pressures: mouth pressure (PM; simulating a mouth-held demand regulator), lung centroid pressure (PLC; + 1.33 kPa relative to the sternal notch), and 0.98 kPa (10 cmH2O) above and below the lung centroid pressure. Inspiratory, expiratory and total flow-resistive pulmonary work were computed from the integration of transpulmonary pressure (difference between oesophageal and mouth pressure) with respect to lung volume change. When breathing air delivered at mouth pressure, immersion significantly elevated all total flow-resistive pulmonary work components (P less than 0.05). Each increment in breathing pressure resulted in a progressive reduction in expiratory and total flow-resistive pulmonary work, so that when air was provided at lung centroid pressure and lung centroid pressure +0.98 kPa both components were similar to control values (P greater than 0.05). Inspiratory was always less than expiratory pulmonary work. During immersion inspiratory pulmonary work was significantly reduced when air supply pressure was increased above mouth pressure (P less than 0.05). Subsequent pressure increments failed to produce further changes in inspiratory pulmonary work. The difference in response between the inspiratory and expiratory components of total flow resistive pulmonary work was attributed primarily to the volume-dependence of the expiratory component. PMID- 1927546 TI - Calcitonin gene-related peptide (CGRP) and leg vascular resistance during head-up tilt induced hypovolaemic shock in man. AB - Calcitonin gene-related peptide is a potent vasodilator and its distribution in perivascular nerves suggests a role in the regulation of vascular tone. We evaluated leg vascular resistance together with total peripheral resistance and the arterial plasma concentrations of calcitonin gene-related peptide and catecholamines during 50 degrees head-up tilt induced hypotension in 7 males. During tilt mean arterial pressure, heart rate, total peripheral resistance, leg vascular resistance and plasma noradrenaline increased, while cardiac output and leg blood flow decreased. After 45 +/- 9 min (mean +/- SE) presyncopal symptoms appeared together with decreases in mean arterial pressure (81 +/- 6 to 56 +/- 9 mmHg), heart rate (97 +/- 6 to 73 +/- 8 beats min-1), leg vascular resistance (158 +/- 9 to 109 +/- 8 mmHg min l-1) and total peripheral resistance (17 +/- 3 to 10 +/- 2 mmHg min l-1) (P less than 0.01). Plasma calcitonin gene-related peptide increased from 32 +/- 3 to 35 +/- 3 pmol l-1 (P less than 0.01) and adrenaline from 1.1 +/- 0.2 to 1.7 +/- 0.3 nmol l-1 (P less than 0.01), while noradrenaline did not change. The results indicate that presyncopal symptoms induced by head-up tilt are associated with regional as well as total decreases in vascular resistance accompanied by moderate increases in arterial plasma concentrations of calcitonin gene-related peptide and adrenaline. PMID- 1927547 TI - Myogenic responsiveness in rat hindquarter vessels during constant-flow and constant-pressure perfusion in vitro; effects of various potassium concentrations and of endothelial nitrous oxide blockade. AB - An in vitro constant-flow, alternatively constant-pressure, perfusion method for studying microvascular myogenic responsiveness in otherwise intact rat hindquarters was used to explore how three types of influences affect the pressure-flow induced enhancements of myogenic tone: (1) Changes of potassium concentration over the range 2-50 mmol; (2) Whether myogenic responsiveness, which is fairly weak during these conditions of high shear rates, is enhanced by blockade of endothelial prostacyclin and nitrous oxide formation; (3) Whether some of the drawbacks of the constant-flow technique, like rapid edema formation, is offset by a constant-pressure variant. The result can be summed up as follows. (1) Myogenic responsiveness is also during in vitro conditions markedly influenced by even modest potassium concentration changes around the physiological resting level, e.g. showing a fourfold difference between potassium concentrations of 2.5-4.5 mmol. It was entirely suppressed above 7-8 mmol potassium concentration but also when potassium concentration values above 20 mmol increasingly depolarize and constrict the resistance vessels. (2) While blockade of prostacyclin synthesis was without effect, suppression of endothelial nitrous oxide production could increase myogenic responsiveness up to fourfold, suggesting that shear-stress dependent release of this agent serves to suppress myogenic activity. These effects were, however, quite variable suggesting that also other endothelial inhibitory influences are involved. (3) The constant pressure variant reduces some of the methodological drawbacks, particularly the oedema formation which can be further reduced by increasing perfusate colloid osmotic pressure. However, interferences by the mentioned, partly unknown endothelial mechanisms still tend to suppress myogenic responsiveness to a varying extent, which hampers quantitative analyses particularly of other inhibitory influences. PMID- 1927548 TI - Comparative studies of the venous resistance and capacitance functions and their sympathetic regulation in skeletal muscle. AB - The relation between the capacitance response (regional blood volume mobilization) and the venous resistance response, i.e. the two main functions of the venous system, was investigated during graded sympathetic nerve excitation in cat gastrocnemius muscle under well defined experimental conditions. The neural capacitance response was also compared with the total regional vascular resistance response and its precapillary resistance component. A reliable distinction between precapillary and postcapillary resistance reactions was made possible by a whole-organ technique permitting continuous recordings of hydrostatic capillary pressure. In the control state, in which a transcapillary fluid equilibrium prevailed, total regional vascular resistance response, precapillary resistance component and venous resistance response averaged 16.6, 14.5 and 2.1 PRU, respectively and total regional blood volume was calculated to comprise 1.0 ml 100 g tissue-1. Graded sympathetic activation, causing graded increments in total regional vascular resistance response, precapillary resistance component and venous resistance response by maximum values of 96, 88 and 8 PRU respectively, were associated with graded decrease in total regional blood volume, at maximum by an average value of 0.57 ml 100 g tissue-1. The relations between regional blood volume mobilization on the one hand, and total regional vascular resistance response, precapillary resistance component and venous resistance response on the other, were all non-linear, implying that the sympathetic volume decrease per unit resistance increase was greater for small than large resistance increases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927549 TI - Effects of airway luminal concentration of albumin on histamine-induced mucosal exudation of radio-iodine labelled albumin. AB - In an in vivo study of guinea-pig airway barriers we have examined the effects of the luminal concentration of albumin on exudation (outward) and absorption (inward) permeabilities to radio-iodine labelled albumin. Previously validated techniques for superfusion of solutes onto the tracheobronchial mucosal surface and for subsequent tracheal lavage were employed. [125I]albumin was administered intravenously as plasma tracer and [131I]albumin was superfused topically as absorption tracer. Histamine (5.0 nmol) was superfused onto the mucosal surface together with the absorption tracer and in the presence of different albumin concentrations (0.3, 3.0 and 30 mg ml-1). The experiment was terminated 10 minutes after the tracheal mucosal superfusion and samples of plasma and tracheal lavage fluid were collected. The mucosal exudation response was calculated from the detection of [125I]albumin in the airway lumen. The absorption ability of the mucosa was determined by the detection of [131I]albumin in circulating plasma. Histamine induced a significant mucosal exudation of [125I]albumin. This effect was unaffected by the level of albumin on the mucosal surface. There was a small but significant absorption of [131I]albumin in the presence of 0.3 and 3.0 mg ml 1 of albumin in the luminal liquid. An albumin concentration of 30 mg ml-1 markedly increased the rate of absorption of [131I]albumin. However, the absorption rate was not affected by the histamine-induced mucosal exudation process at any level of luminal albumin. The present data further demonstrates that plasma exudation and mucosal absorption are independent processes. The data are in keeping with the view that an increased subepithelial hydrostatic pressure moves the plasma exudate across the mucosa as a distinct outward process. PMID- 1927550 TI - Antisecretory effect of splanchnic nerve stimulation on choleratoxin-induced secretion in the cat, an effect mediated at the crypts. AB - The experiments were performed on cats anaesthetized with alpha-chloralose. Segments of the small intestine were perfused with sodium-free hypotonic choline mannitol solution and intestinal net fluid transport was recorded with a volumetric technique. The content of sodium and chloride in the lamina propria of the small intestinal villus was measured with an electron microprobe in freeze dried paraffin embedded tissue. In absorbing control intestine, there was an even distribution of electrolytes along the villi. Sympathetic nerve stimulation (5 Hz, 5 ms, 5 V) did not significantly affect electrolyte distribution and net fluid transport. Intestinal secretion was elicited by pretreatment of the intestine with cholera toxin. The concentration of sodium and chloride was elevated in the apical third of the villi in intestines during the secretion since secreted sodium from the crypts was reabsorbed into the villi. Sympathetic nerve stimulation decreased the cholera secretion significantly in intestines pretreated with cholera-toxin. Furthermore, the apical gradients of sodium and chloride in the villi, caused by the reabsorbed sodium and chloride, disappeared during sympathetic nerve stimulation. It is concluded that, in the used experimental model, the antisecretory effect of sympathetic nerve stimulation was caused by inhibition of crypt secretion and not by augmented villus absorption. PMID- 1927551 TI - Adaptive response of ileal mucosa to malnutrition in the rat: role of polyamines. AB - Mucosal disaccharidases and ornithine decarboxylase activities were measured in malnourished, preweaning (19 days), post weaning (24 days) and young adult (37 days) rats. Malnutrition resulted in decreased body weight, intestinal weight, DNA and protein content. Mucosal Prot/DNA ratios were elevated in the ileal segments of the 24 and 37 day rats. Preweaned malnourished rats had significantly enhanced lactase specific activity in both jejunal and ileal segments. Adult malnourished rats showed enhanced jejunal lactase and sucrase activities which were not accompanied by elevated ornithine decarboxylase values. Mucosal sucrase and ornithine decarboxylase specific activities were significantly elevated in the ileal segment of the 24 and 37 day old malnourished rats. Studies of adult rats showed that these increased specific activities were located in the mature enterocytes at the villus tip, and persisted during a 24 h diurnal cycle. DFMO administration for 4 days completely inhibited mucosal ornithine decarboxylase and abolished the rise of ileal sucrase activity. We concluded that the intestinal response to reduced food intake is age related and differs in the jejunum and ileum: ornithine decarboxylase and polyamines are involved in ileal adaptation to malnutrition in postweaned and adult rats. PMID- 1927552 TI - Cholecystokinin-stimulated insulin secretion and protein kinase C in rat pancreatic islets. AB - In isolated rat pancreatic islets, the possible involvement of protein kinase C in cholecystokinin-8-stimulated insulin secretion was investigated. In islets exposed for 24 hours to the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (500 nmol l-1), a procedure known to down-regulate islet protein kinase C activity, the insulinotropic effect of cholecystokinin-8 (10(-7) mol l-1) was partially reduced (by 34 +/- 8%, P less than 0.001). In contrast the insulinotropic response to acute exposure to 12-O-tetradecanoyl phorbol 13 acetate (10(-6) mol l-1) was totally abolished (P less than 0.001), whereas the insulin response to glucose (8.3 mmol l-1) was not affected. In normal islets, the protein kinase C-inhibitor, staurosporine, inhibited 12-O-tetradecanoyl phorbol 13-acetate- and glucose-stimulated insulin secretion (P less than 0.01), but was without effect on cholecystokinin-8-stimulated insulin release. Furthermore, in normal islets, cholecystokinin-8 had no effect on insulin release at a low glucose level (3.3 mmol l-1). However, at this low glucose level, cholecystokinin-8 clearly potentiated insulin release induced by acute exposure to 12-O-tetradecanoyl phorbol 13-acetate (10(-8) -10(-6) mol l-1, P less than 0.001). This potentiating effect was abolished by the removal of extracellular Ca2+. It is concluded that the insulinotropic effect of cholecystokinin-8 in rat islets is partially mediated by the protein kinase C pathway. Furthermore, the lack of effect of cholecystokinin-8 on insulin secretion at a low glucose level might be explained by an insufficient activation of protein kinase C under these conditions. PMID- 1927553 TI - Different metabolic regulation by adenosine in omental and subcutaneous adipose tissue. AB - Adenosine content was higher in omental adipose tissue (0.91 +/- 0.13 nmol g-1 of wet weight; mean +/- S.E.M.) than in abdominal subcutaneous adipose tissue (0.42 +/- 0.08 nmol g-1 of wet weight) in rapidly frozen surgical biopsy samples taken from ten patients undergoing elective abdominal surgery. This difference was statistically significant (P less than 0.002). The sensitivity of isoprenaline stimulated lipolysis to inhibition by N6-(phenylisopropyl)adenosine was studied in omental and abdominal subcutaneous adipocytes isolated from nine patients. The effect of this adenosine Ri-site agonist was less pronounced in omental than in abdominal subcutaneous adipocytes which could be due to a desensitization phenomenon. This difference was statistically significant (P = 0.012). The ratio of the inhibitory guanine nucleotide binding proteins Gi1 and Gi2 to the corresponding stimulatory protein Gs was the same in plasma membranes prepared from omental and abdominal subcutaneous adipocytes. In conclusion, in omental adipose tissue, adenosine content is higher and the response to this nucleoside is less pronounced than in subcutaneous adipocytes. This difference cannot be explained by a different (Gi1 + Gi2)/Gs ratio. PMID- 1927554 TI - Operation Everest II: structural adaptations in skeletal muscle in response to extreme simulated altitude. AB - Alterations in skeletal muscle structure were investigated in 6 male subjects who underwent 40 days of progressive decompression in a hypobaric chamber simulating an ascent to the summit of Mount Everest. Needle biopsies were obtained from vastus lateralis of 5 subjects before and immediately after confinement in the chamber, and were examined for various structural and ultrastructural parameters. In addition, total muscle area was calculated in 6 subjects from CT scans of the thighs and upper arms. Muscle area at these sites was found to decrease significantly (by 13 and 15%) as a result of the hypobaric confinement. This was substantiated by significant (25%) decreases in cross sectional fibre areas of the Type I fibres and 26% decreases (non significant) in Type II fibre area. Capillary to fibre ratios remained unchanged following hypoxia as did capillary density although there was a trend (non significant) towards an increase in capillary density. There were no significant increases in mitochondrial volume density or other morphometric parameters. These data indicate that chronic, severe hypoxia on its own does not result in an increase in absolute muscle capillary number or a de novo synthesis of mitochondria. The trends toward an increase in capillary density and mitochondrial volume density were interpreted as being secondary occurrences in response to the pronounced muscle atrophy which occurred. PMID- 1927555 TI - Acute effects of alcohol on unit activity in the motor cortex of freely moving rabbits: comparison with the limbic cortex. AB - Unit activity was recorded from the motor cortex of eight freely moving rabbits in order to examine the acute effect of ethanol (1 g kg-1) on organization of unit activity and to compare it with our earlier results from the limbic cortex. The rabbits performed a food-acquisition task in the experimental cage. Unit activity was recorded during behaviour in the control experiment followed by the alcohol experiment on the next day. After ethanol, behavioural mistakes and the duration of the behavioural cycle significantly increased. In the control experiments activation of 58% of the units had no constant relation to the phases of the behavioural cycle (non-involved units), whereas 42% of the units were constantly activated during certain phases (involved units). Two per cent of the latter units were activated in relation to newly learned behavioural acts (e.g. pedal pressing; L units), 28% in relation to food seizure and/or grinding (S units) and 12% in relation to certain movements during different behavioural acts (M units). Ethanol had no effect on the number of active units and the same relation between the number of non-involved and involved units or between the number of different types of involved units was found. However, the number of involved units decreased in the upper and increased in the lower cortical layers. Also the number of units with low background frequency increased, although the frequency within activations did not change. In our earlier study the number of active units in the limbic cortex decreased after ethanol by one third and the relation between the number of L and M units was reversed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927556 TI - Children in sauna: hormonal adjustments to intensive short thermal stress. AB - Hormonal response to Finnish sauna bath was investigated in 20 prepubertal children (age 5-10 years). Blood leukocyte count, plasma potassium, serum aldosterone, growth hormone and prolactin concentrations increased; plasma volume, plasma sodium, catecholamines, serum antidiuretic hormone, atrial natriuretic peptide (ANP), cortisol, and thyrotropin concentrations remained unchanged during sauna bath. One hour after sauna, serum thyrotropin, atrial natriuretic peptide and blood glucose concentrations decreased, whereas the rest of the hormones remained unchanged. Our results implicate that maintenance of homeothermia resulted in moderate hormonal changes in children during Finnish sauna bath which indicate similar adequate hormonal thermoregulatory adjustment as previously documented in adults. PMID- 1927557 TI - Affective symptoms associated with the onset of major depression in the community: findings from the US National Institute of Mental Health Epidemiologic Catchment Area Program. AB - This study examined the strength of relationships between forms of depressive symptoms over a one-year period and the onset of major depression. The data analyzed were collected in 4 sites of the US National Institute of Mental Health Epidemiologic Catchment Area Program (NIMH-ECA, 1981-1985). The Diagnostic Interview Schedule's specifications of DSM-III criteria for major depression were employed. Overall, the results indicated a strong positive association between an onset episode and the following depressive symptoms over 1 year: diminished sexual drive, feelings of worthlessness or excessive guilt and trouble concentrating or thinking. Sleep disturbance among women and fatigue among males were also significantly associated with experiencing an onset of major depression. The implications of the findings for secondary prevention efforts are explored. PMID- 1927558 TI - Validity and reliability of the Dysfunctional Behaviour Rating Instrument. AB - The objective of this study was to examine the reliability and validity of the Dysfunctional Behaviour Rating Instrument (DBRI) in cognitively impaired older adults living in the community. A total of 184 adults with suspected cognitive impairment received a standardized history, physical examination and work-up that included the Standardized Mini-Mental State Examination. Caregivers scored a DBRI Behaviour Problem Checklist (BPC) and Lawton Scale for each patient. The reliability of the DBRI, measured by an intraclass correlation coefficient, was 0.75. The correlation coefficient between the DBRI and the BPC total score was 0.71. The correlations between the DBRI and the cognitive, activities of daily living and self-care domain scores of the BPC were lower (0.66, 0.38 and 0.26 respectively). The DBRI is a specific, reliable and valid caregiver-reported measure of dysfunctional behaviour in cognitively impaired elderly living in the community. PMID- 1927559 TI - Serotonergic interhemispheric asymmetry: gender difference in the orbital cortex. AB - The asymmetry of tritiated imipramine (IMI) binding sites (which are associated with serotonergic mechanisms) were investigated in the orbital frontal cortex in 6 women and men who died of natural causes, and who did not have a history of mental disorders. There was significant interhemispheric asymmetry in both sexes, higher Bmax on the right side compared with the left. The Bmax values of IMI binding in the right orbital cortex in women were significantly higher than in men. Our preliminary findings--gender difference of serotonergic mechanisms in some area of the human brain--are in accordance with the observed gender differences in a variety of serotonin-regulated behaviors (sexual behavior, aggression and impulse control), and serotonergic mental disorders (eating disorders, suicidal behavior, anxiety disorders and depression). PMID- 1927560 TI - Penis-root perception of Koro patients. AB - Koro is an acute anxiety reaction in which the perception of decreased penis length because of intra-abdominal traction is the main feature. This study attempts to explore the penis-root perception of the Koro patients by a graphomotor projective test--the Draw-a-penis Test (DAPT). This controlled DAPT investigation shows that Koro patients perceived the penis as a detached organ with root-boundary definiteness as evidenced from their close penis-root perception. They also displayed reduced volumetric perception of penis-root than the normal subjects. These perceptual deviations in penis-root image are discussed in relation to their Koro vulnerability. PMID- 1927561 TI - The concept of cycloid psychosis: the discriminatory power of symptoms. AB - Records of all 154 psychotic patients first admitted to a psychiatric hospital in 1925 were rated according to a checklist of 33 dichotomous items expected to characterize cycloid and schizoaffective psychosis; 64 cases satisfied 5 or more items. Among them, 34 were globally judged as cycloid and showed a favourable outcome when followed up. The remaining 30 cases were used as a contrast sample, consisting of schizoaffective psychotics with an unfavourable outcome and schizophrenics and affective patients who shared some symptoms with the experiment group. Six symptoms significantly more frequent in the cycloid group were all characteristic for confusional and anxiety or happiness psychoses in the sense of Leonhard. Happiness-ecstacy and global altruism were exclusively recorded in cycloid psychosis. A discriminant analysis yielded a significant proportion of correct predictions. The result was thought to be relevant for differential therapeutic strategies. PMID- 1927562 TI - A comparison of the mental status, personality profiles and life events of patients with irritable bowel syndrome and peptic ulcer disease. AB - Forty patients with a diagnosis of irritable bowel syndrome (IBS) and 32 patients with peptic ulcer disease underwent a full psychiatric assessment. All were rated using the Gastrointestinal Symptom Rating Scale (GSRS), the Comprehensive Psychopathological Rating Scale, the Life Experiences Survey and the Eysenck Personality Inventory. The 2 groups were not distinguishable on total GSRS scores or rates of DSM-III diagnosed mental disorder. However, greater trait scores for neuroticism and introversion were found in the IBS group, together with a greater reporting of life events perceived as negative. PMID- 1927563 TI - Platelet imipramine binding and serotonin uptake in obsessive-compulsive patients. AB - Platelet imipramine binding was measured in 16 drug-free nondepressed patients (aged 20-61 years, mean +/- SD 35 +/- 8) suffering from obsessive-compulsive disorder (OCD) and in 16 sex-, race- and age-matched healthy controls. Imipramine binding capacity and affinity were not different in the 2 groups. Platelet serotonin (5-HT) uptake capacity, Vmax, was also measured in 15 of these patients and their matched controls. Vmax was significantly higher in the patients (309 +/ 149 pmol/10(9) cells/min) than in the controls (181 +/- 110). An increase in platelet 5-HT uptake supports the involvement of 5-HT in OCD and may suggest that a hyperactive serotonergic system is present in this disorder. PMID- 1927564 TI - Rapid eye movement latency and mood following a delay of bedtime in healthy subjects: do the effects mimic changes in depressive illness? AB - The phase advance hypothesis proposes that a phase advance of certain circadian rhythms (such as rapid eye movement (REM) sleep propensity) relative to the sleep wake cycle is implicated in the pathophysiology and pathogenesis of depression. In an earlier study, we reported that a 6-h delay of sleep in normals produced REM changes that resembled the depressive pattern. Mood change was generally modest, although 2 of the 10 subjects became noticeably depressed. This study assessed the replicability of these results, and introduced a phase advance control condition. Predicted changes were observed in REM parameters. Modest but reliable mood change was confined to the first night of the phase delay, and was attributed to sleep loss. These results suggest that the effects of the phase shift were relatively benign, except in a minority of cases. Such individuals may have a susceptibility to depression that manifests itself under certain conductive physiological conditions. PMID- 1927565 TI - Child and adolescent psychiatric patients in adulthood. AB - A total of 142 consecutive patients cared for by child and adolescent psychiatry were followed up to the age of 33-37 years; 49% were treated in adult psychiatry between the ages of 20-25 years, and 20% of these were hospitalized. The frequency of hospitalization was 4-5 times that of a control group. Between the ages of 20-34 years, 32% were admitted some time for inpatient psychiatric care. Psychiatric diagnoses of the patients: schizophrenia 4%, manic-depressive 5%, neurosis and reactive insufficiency 11%, personality disorders and/or abuse diagnosis 12%. Patients with a schizophrenia diagnosis in adulthood needed the most hospitalization. The symptom picture was stable from child and adolescent psychiatric care through to adulthood, but abuse increased with age. The frequency of sick leave was 2.5 times higher among the child and adolescent psychiatric care patients than among the control group. At the age of 34-36 years, 13% of the former patients received disability benefits as compared with 1% for the same age groups in the entire population of Sweden. Twenty-one percent received sentences for criminal offenses from the age of 20-34 years. The number of crimes decreased with increasing age. Nearly 50% were in contact with the social welfare services, 3 times as many as in the control group. A third of the men completed their national military service. A total of 6 men and 1 woman died, indicating an increased mortality rate for men. All deaths except one were related to the mental disorder. PMID- 1927566 TI - Relationships between personality development, interpersonal perception and communication in parents of schizophrenics, psychiatric controls and normal subjects. AB - Employing a family interaction paradigm, the psychodynamic development of personality (Consensus Spouse-Rorschach, CSR), mutuality in interpersonal perception (Interpersonal Perception Method), and feedback mechanisms in communication (the Confirmation-Disconfirmation Coding System) were investigated. The subjects were 66 parents (33 couples) whose offspring were as follows: 12 schizophrenics (RDC, DSM-III, DSM-III-R), 12 with other mental disorders, and 9 subjects with no mental disorder. Communication was observed in 2 situations, using CSR and the Colour Conflict Method. Feedback mechanisms in parent communication, previously found to be associated with offspring mental disorder, were associated both with lack of mutuality in interpersonal perception and low personality development. Lack of mutuality was associated with low parent personality development. The results emphasize the usefulness of monitoring both parent personality development (family structure), mutuality in interpersonal perception (family phenomenology), and communication (family behaviour) when assessing interaction in families of patients with severe mental disorder. They also point to a need for theoretical integration between the different concepts of family interaction of different clinical and theoretical traditions. PMID- 1927567 TI - Perception of early parenting in panic and agoraphobia. AB - Thirty-two patients with a DSM-III-R diagnosis of panic disorder (PD) were administered the Parental Bonding Instrument (PBI), a 25-item self-report questionnaire devised to evaluate parental rearing practices. Compared with 32 matched healthy controls, PD patients scored both their parents as being significantly less caring and more overprotective. Moreover, the consistency of parental attitudes between the 2 parents was significantly lower, indicating lesser uniformity in the rearing patterns. PMID- 1927568 TI - A 30-year follow-up study of a child psychiatric clientele. II. Psychiatric morbidity. AB - Psychiatric morbidity, expressed as hospital admissions during a 30-year follow up period, was studied among 322 former child psychiatric patients, who were admitted from 1949-1951, and who were followed up as of December 31, 1980. A total of 115 patients (36%)--55 boys (29%) and 60 girls (45%)--had been admitted to an adult psychiatric department, with 50 patients having only one admission. The mean age at the time of the study was 39 years. The former child psychiatric patients were admitted to adult psychiatric hospitals 50 times more often than comparable age groups from the general population. At all times women had a higher prevalence of admission. The cumulative percentage of first admissions of men was almost unchanged during the last 10 years of the follow-up period, and the figure for women was gradually increasing. The longitudinal course of mental disorders in the sample, measured as psychiatric admissions, was studied in relation to age at the time of admission to the child psychiatric department. The results consistently showed that older age of admission as a child meant fewer psychiatric admissions as an adult during the follow-up period. A total of 39 of the psychiatrically admitted patients (34%) had been granted a disability pension. A total of 7 patients (6%) died during the study period, including 2 patients who committed suicide. By the variables employed, 37% of the sample were judged to have had a good overall outcome, with diagnosis being an inconsistent predictor of outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927569 TI - Personality disorders 2-5 years after treatment: a prospective follow-up study. AB - Ninety-seven patients consecutively admitted to a day unit specializing in the treatment of personality disorders were included in a prospective follow-up study. At follow-up an average of 3 years after index admission, patients with borderline personality disorder (BPD) displayed a moderate symptom reduction and a fair global outcome. Patients with schizotypal personality disorder (STP) showed a similar reduction in symptoms but retained relatively poor global functioning. Individuals with cluster C personality disorders, in contrast, showed both a good global outcome and a marked symptom reduction. STP individuals were the least socially adjusted, employed and self-supporting of all diagnostic subgroups. STP and BPD individuals had far more inpatient treatment in the follow up period than other groups. The overall suicide rate was low compared with most similar studies. PMID- 1927570 TI - Adjustment reactions: a long-term prospective and retrospective follow-up of former patients in a crisis intervention ward. AB - The results of a 5-year follow-up study of 76 patients in a crisis intervention ward who were suffering from an adjustment reaction (brief or prolonged depressive reaction) according to ICD-9 criteria indicate a rather favorable course and outcome using standardized instruments. Only 17% developed a chronic or severe course of primarily depressive symptoms and only 1 (2%) patient committed suicide after discharge, whereas 64% had a very favorable and 18% a favorable course and outcome. This result is reflected in a rather low use of psychiatric and psychotherapeutic outpatient services during the follow-up period. PMID- 1927571 TI - Sexuality of women with anorexia nervosa. AB - The sexual development and life of 30 adult women with anorexia nervosa and of 50 control women was investigated using a structured interview and 3 sexological questionnaires. Heterosexual development was found to be normal in the initial stages, but psychosexual adaptation in adulthood was impaired. Primary or secondary insufficiencies of sexual life were found for 80% of the anorectic patients. Biological and psychosocial factors may participate in this unfavourable state. Discussion of sexual problems should be part of the process of treating women with anorexia nervosa. PMID- 1927572 TI - Adolescents and benzodiazepines: prescribed use, self-medication and intoxication. AB - In a longitudinal study of 1230 people aged 13-18 years from the Greater Oslo Area, the past-year prevalence of anxiolytic or hypnotic use was 10%, which is higher than previously reported. The majority gave therapeutic reasons as a motive for using these drugs. However, most of the use was unprescribed. The parents, and especially the mother, were the most important suppliers. A minority gave intoxication as a motive for using these drugs. In this group, the suppliers were mainly peers and the illegal market. Neither the unprescribed nor the prescribed therapeutic use show any association with use of drugs such as alcohol and cannabis. There is, however, a strong association between the unprescribed use of benzodiazepines by young people and by their parents. This suggests a pattern of learning and role modelling, which must be regarded as problematic for public health policy. Those who use the drugs to become intoxicated have particularly poor mental health, and they use many other drugs as well. This group probably runs a special risk of developing more serious drug abuse. PMID- 1927573 TI - Disposition of the neuroleptic zuclopenthixol cosegregates with the polymorphic hydroxylation of debrisoquine in humans. AB - The pharmacokinetics of a single oral dose of the neuroleptic drug zuclopenthixol (10 or 6 mg) was studied in 6 extensive and 6 poor metabolizers of debrisoquine. The peak plasma concentrations of zuclopenthixol did not differ between the phenotypes, whereas the plasma elimination half-life was significantly longer in poor than in extensive metabolizers (29.9 +/- 6.6 vs 17.6 +/- 6.9 h). Accordingly, the total oral plasma clearance was lower in poor than in extensive metabolizers (0.78 +/- 0.27 vs 2.12 +/- 0.65 1/h/kg). Ten of the volunteers had previously participated in a similar study in which the kinetics of perphenazine, another neuroleptic drug, were studied in poor and in extensive metabolizers of debrisoquine. There was a significant correlation between the oral clearance of perphenazine and that of zuclopenthixol among these 10 subjects. The study indicates that the disposition of zuclopenthixol, as well as that of perphenazine, is related to the genetically determined capacity to hydroxylate debrisoquine. The significance of this polymorphism for the clinical use of neuroleptics is discussed. PMID- 1927574 TI - Importance of precue location in directing attention. AB - In location-precuing experiments, accuracy in discrimination of T-like characters improves with increasing time between the precue and the target. In this experiment, two central and two peripheral cue locations were examined using 13 different cue-target intervals from 0 to 234 msec. Accuracy was the same when trials were cued from the two peripheral locations (two thirds distance between fixation and target or distal to the target location). Centrally cued trials (cues at fixation or next to fixation) resulted in slower onset of attentional effects than peripherally cued trials, but there was greater accuracy at long cue target intervals for central than for peripheral cues. Data are compared to previously published research. PMID- 1927575 TI - Why anamorphoses look as they do: an experimental study. AB - The aim of this research was to understand why anamorphic images break up until they are unrecognizable when the observer's eye moves away from the regularization point. An experimental device was set up allowing the anamorphic deformation of images, consisting of a rotating screen on which figures were projected. The point from which subjects observed the screen was far from the projecting point. The projected figures lengthened equally when the screen rotated either clockwise or counterclockwise. On the other hand, the perceptual result was the opposite: in the former case, a rigid figure was seen rotating around its own vertical axis; in the latter case, the same figure was seen elongating or shortening in a non-rigid manner, without rotating. Since we were in a projective condition, the invariance of the cross-ratio was maintained. Therefore, we were in a situation of non-rigidity, in spite of the invariance of the cross-ratio. Three stimuli, white on a black background, were used in experiment 1. They were a segment, three aligned points, and four aligned points. Subjects had to rotate the screen at will and stop it at the point when they saw the transformation of movement from rigid rotation to non-rigid elongation. The results showed that: (i) in spite of being a projective invariant, the cross ratio is not always a perceptual invariant too; (ii) the threshold screen position between the two motions was located at the position where the modifications of the solid angle subtended to the stimulus assumed a different trend from that of a sinusoid. Two stimuli were used in experiment 2: a continuous segment and one intersected by four vertical lines. The aim was the same as for experiment 1, but subjects had to repeat it from five different points of observation. The results showed that: (1) there was no significant difference depending on type of stimulus, indicating that the computability of the cross-ratio is not a necessary condition for the execution of the task; (2) the more the observer moved away from the projection axis, the more evident the distortion of the stimulus appeared, in accordance with what happens when observing an anamorphosis; (3) when the metamorphosis from rigid motion to elastic motion was seen the visual angle subtended to the stimulus was constant for all distances from the projection axis, in accordance with the hypothesis of rigidity. PMID- 1927576 TI - Effects of preliminary information in a Go versus No-go task. AB - A series of studies using a Go versus No-go task examined the question of whether preliminary information available early in the recognition of a stimulus is made available to later processes before stimulus recognition is finished, a question relevant to the controversy between discrete and continuous models. Experiment 1 showed that a Go response is faster following a cue indicating that the response probably would be required than following a cue indicating it probably would not be required. Experiments 2-7 were conducted to find out whether analogous preparation occurred when probability of the Go response was signalled by easily discriminable features of a single stimulus rather than a separate cue. The effect was observed when the easily discriminable features uniquely determined the name of the stimulus letter, but not when they merely indicated that the stimulus name was one of two visually similar letters. These results are consistent with the Asynchronous Discrete Coding model, in which the perceptual system makes available to later processes only preliminary information corresponding to discretely activated stimulus attributes. PMID- 1927577 TI - Hemorrhagic ovarian cyst detection by transvaginal sonography: the great imitator. AB - The sonograms of 102 hemorrhagic ovarian cysts (HOC) were reviewed to ascertain the full spectrum of sonographic findings as visualized by transvaginal sonography (TVS). The diagnoses, in 11 cases, were proven by surgery and the rest have undergone conservative follow-up until resolution (clinically and sonographically). The accurate diagnosis of HOCs by transabdominal sonography is quite difficult. The appearance of these cysts as visualized by TVS is described. We advise TVS as a better means for identification of HOCs, thus decreasing the rate of diagnostic invasive procedures. PMID- 1927578 TI - Estriol: a weak estrogen or a different hormone? PMID- 1927579 TI - Relationship between serum testosterone and sex hormone binding globulin in menstruating and postmenopausal women. AB - The relationship between total testosterone (T), sex hormone binding globulin (SHBG) and calculated non-SHBG-bound testosterone (NST) was studied in randomly collected blood samples from healthy menstruating (n = 61) and postmenopausal (n = 65) women. In 12 of the menstruating women, blood samples were also collected more frequently during the menstrual cycle. Total T and SHBG were positively correlated in menstruating women in random samples as well as during different phases of the menstrual cycle, but not in postmenopausal women. Upper and lower limits of NST were independent of SHBG in menstruating but not in postmenopausal women. The data are at variance with the common concept about SHBG regulation and suggest a kind of compensatory mechanism in order to maintain a constant androgen homeostasis in menstruating but not in postmenopausal women. Consequently, supranormal total T or subnormal SHBG values do not necessarily indicate hyperandrogenicity in normally menstruating women. PMID- 1927580 TI - Growth factors attenuate the cholinotoxic effects of ethanol during early neuroembryogenesis in the chick embryo. AB - The interaction between growth factors and ethanol on cholinergic neuronal expression was studied in the chick embryo during early neuroembryogenesis using choline acetyltransferase activity as a cholinergic marker. As we have previously reported (Brodie & Vernadakis, Dev. Brain Res. 56: 223-228, 1990; Kentroti and Vernadakis, Dev. Brain Res. 56: 205-210, 1990), ethanol administration in ovo at embryonic days 1-3 produced a 30% decrease in choline acetyltransferase activity. Nerve growth factor and epidermal growth factor administration alone, at embryonic days 1-3, produced a slight increase in choline acetyltransferase activity of both brain and spinal cord when examined at embryonic day 8. Concomitant administration of either nerve growth factor or epidermal growth factor with ethanol eliminated the decrease in choline acetyltransferase activity produced by ethanol. Moreover, administration of either nerve growth factor or epidermal growth factor at embryonic days 4-7 to embryos pretreated with ethanol at days 1-3 raised choline acetyltransferase activity to a level similar to that observed in controls. Thus the growth factors reversed the ethanol-induced cholinergic insult and restored the cholinergic population to normal. These findings provide evidence of a possible role of NGF and EGF in interfering with the neurotoxic effects of ethanol during embryogenesis. PMID- 1927581 TI - Activity of hippocampal extract on development of [3H]5-HT high-affinity uptake in dissociated microcultures. AB - Specific and localized lesions of the 5-HT fibers in the hippocampus induce homotypic collateral sprouting and enhance serotonergic fiber outgrowth from adult neurons and transplanted fetal tissue. In this study, hippocampal extracts were prepared and applied to primary cultures of fetal serotonergic neurons. The effects of plating density and serum additives were examined. The growth of the serotonergic neurons in the rostral brainstem dissociated cultures were estimated by measuring the specific uptake of [3H]5-HT. The results indicate the presence of a trypsin-sensitive factor which is active when prepared fresh at dilutions up to 1/10,000. The factor is higher in hippocampus than cerebellum. Young male tissue contained more activity than either female or aged hippocampus. Although both positive and negative effects are described, higher dilutions of factor (1/1,000) were generally stimulatory in high density cultures while lower dilutions (1/10) were inhibitory in low density cultures. Specific removal of 5 HT hippocampal afferents with fornix-fimbria microinjections of 5,7 dihydroxytryptamine resulted in an initial loss of activity (2 days and 2 weeks) followed by an enhanced activity (2 months) compared to normal hippocampal extract. Several possibilities are discussed as to the identity of the serotonergic growth factor from hippocampal supernatant. PMID- 1927582 TI - Proteoglycan synthesis by clonal skeletal muscle cells during in vitro myogenesis: differences detected in the types and patterns from primary cultures. AB - Proteoglycan synthesis by two clonal murine skeletal muscle cell lines, G8-1 and C2, was examined. Cultures of skeletal muscle cells at both the myoblast and myotube stages were radiolabeled using [35S]sulfate as a precursor. The proteoglycans of the cell layer and medium were separately extracted and isolated by ion exchange chromatography on DEAE-Sephacel followed by gel filtration chromatography on Sepharose CL-2B. The cell layer proteoglycans eluted from Sepharose CL-20 as a single peak with a Kav of 0.66 and contained glycosaminoglycan chains with an average molecular weight of 20,000. The glycosaminoglycan chains were composed of nearly equal mixtures of chondroitin sulfate and heparan sulfate with the exception that C2 myoblast cultures contained larger amounts of heparan sulfate. Of interest, this line differentiates more rapidly in our laboratory than G8-1. The medium proteoglycans also eluted from Sepharose CL-2B as a single peak with a Kav of 0.66 but contained glycosaminoglycan chains with an average molecular weight of 32,000. Based upon enzymatic and chemical analysis, the medium glycosaminoglycan chains were composed of a mixture of chondroitin sulfate (71-80%) and heparin sulfate (19-22%). Following chondroitinase ABC digestion, the predominant disaccharide released from all glycosaminoglycan fractions was chondroitin-4-sulfate. When the extracted cell layer proteoglycans were chromatographed on Sepharose CL-28 in the absence of detergent, a small but consistent proportion (14-18%) eluted in the void volume, suggesting the association of at least a portion of this proteoglycan with cellular lipid. These differences distinguish proteoglycan metabolism in fusing clonal lines from primary muscle cell cultures suggesting their utility in evaluating the contribution of these macromolecules in myogenesis. PMID- 1927583 TI - Ontogeny of MAP2 and GFAP antigens in primary cultures of embryonic chick brain. Effect of substratum, oxygen tension, serum and Ara-C. AB - Brain cells from embryonic chick (stage 28-29) were cultivated for 16 days under serum-free conditions. Nerve cells were found to mature during the first 7 days in culture, as indicated by the presence and developmental pattern of the relative amount of dendritic-specific microtubule-associated protein type 2 (MAP2). Maximal amounts of MAP2 antigen were found to be directly correlated with the number of cells plated out. Astroglia cell proliferation and differentiation, as measured by the amounts of glial fibrillary acidic protein (GFAP), were found to stabilize after a certain astrocyte cell density was reached. Variation in culture plate coating procedure, oxygen tension and addition of serum or of the cytostatic drug Ara-C were found to differently affect viability and maturation processes of astroglia and of nerve cells. Moreover, optimal culture conditions for long-term brain cell cultures are described. PMID- 1927584 TI - Development of binding sites for excitatory amino acids in cultured cerebral cortex neurons. AB - Binding of [3H]glutamate, [3H]AMPA (RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolo propionate) and [3H]kainate was investigated in membranes prepared from cerebral cortex of 4-day-old and adult mice and from cerebral cortex neurons cultured for different periods of time (2, 4, 8 and 14 days). For all ligands, the number of binding sites increased as a function of development both in vivo and in culture. A significant number of binding sites for the ligands could be demonstrated on the cultured neurons already after 2 days in culture. Scatchard analysis of the binding data showed a single population of binding sites for glutamate (KD approximately 200 nM) and kainate (approximately 6 nM) regardless of the developmental stage in vivo or in culture. In case of [3H] AMPA binding two binding sites with KD values of approximately 6 nM and 100-200 nM could be demonstrated both in vivo and in culture. Binding of [3H]glutamate to cultured neurons could be displaced by N-methyl-D-aspartate (100 microM) and quisqualate (3 microM) in an additive manner but D,L-4-aminophosphonobutyrate (100 microM) had no effect. AMPA binding to cultured neurons was much more (40-fold) sensitive than kainate binding to the newly developed AMPA selective antagonist NBQX (2,3 dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline) indicating that kainate and AMPA bind to independent binding sites. Monitoring membrane potentials in the cultured neurons using the lipophilic cation TPP+ (tetraphenylphosphonium) it was demonstrated that potassium (55 mM) as well as glutamate, AMPA and kainate (100 microM) could depolarize the neurons both at early (2 days) and late (9 days) developmental stages in culture. The demonstration of functionally active receptors for the 3 excitatory amino acids in both immature (2 days in culture) and mature (8-9 days in culture) neurons is discussed in the light of previous studies of the development as a function of the culture period of effects of excitatory amino acids in neurons. It is concluded that no simple correlation exists between expression of binding sites for the excitatory amino acids and their ability to induce cytotoxicity and neurotransmitter release. PMID- 1927585 TI - A sensitive period in gestation for nicotine acceleration of neuromuscular maturation. AB - Nicotine, administered to pregnant Sprague-Dawley rat dams during gestation, altered the maturation of the developing extensor digitorum longus (EDL) muscle peroneal nerve complex of the 2-week-old offspring. Initial isometric twitch time to peak and rate of rise of tension and tetanus time to peak tension of the group treated with nicotine during gestational (G) days G3-G8 were faster than controls indicating accelerated maturation of EDL muscle. Contractile parameters of the group treated with nicotine during G9-G13, a period immediately prior to muscle innervation, differed little from control. Nicotine administered during G14-G21 significantly increased twitch and tetanus tension and twitch rate of rise. There was little to no effect on motor unit size or number of motor units with nicotine during any of the three prenatal periods. Thus, while late prenatal nicotine administration primarily altered the strength of muscle, early gestational administration of nicotine increased the rate of muscle development suggesting a possible sensitive period for the accelerative action of nicotine on muscle maturation at this time. PMID- 1927586 TI - The effects of pseudoephedrine on blood pressure in patients with controlled, uncomplicated hypertension: a randomized, double-blind, placebo-controlled trial. AB - Pseudoephedrine is frequently used as a decongestant. Because of concern about the safety of pseudoephedrine in hypertensive patients, a clinical trial was conducted to determine whether blood pressure control was actually affected by this drug in a selected group of patients with hypertension. Twenty-nine patients with controlled, uncomplicated hypertension, who received drug therapy and ranged in age from 25 to 50 years, were randomized to a treatment or a control group. Subjects took either 60 mg of pseudoephedrine or placebo capsules four times a day for 3 days. From 0800 hours until 2200 hours each day, the subjects obtained hourly blood pressure measurements using a portable sphygmomanometer. An analysis of variance with repeated measures was calculated to determine group differences for systolic and diastolic readings. No statistically or clinically significant differences were found. Therapeutic doses of pseudoephedrine did not adversely affect control of hypertension in these selected patients. PMID- 1927587 TI - Recognizing depression: a comparison of family physician ratings, self-report, and interview measures. AB - Major depressive disorder is the most common diagnosis encountered in family practice, yet family physicians are relatively unlikely to make the diagnosis. This study compared physician ratings of depression with scores from the Center for Epidemiological Studies-Depression (CES-D) questionnaire and with telephone interview diagnoses of depression using the 3rd revised edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria for major depressive disorder in a population of 266 patients in community-based family practices. Additional assessments were made of health status, stress, social support, prescribed psychotropic medication, and counseling. The prevalence of positive questionnaire scores in this population was 22.6 percent, and the prevalence of major depressive disorder (based on telephone interview) was 8 percent. Physician ratings of depression were relatively inaccurate when compared with either CES-D scores or telephone interview diagnoses. Optimum specificity (80 percent) and sensitivity (50 percent) with telephone interview diagnoses were achieved when physicians rated the patient as having any depression versus having no depression. Physician ratings of depression were correlated with their assessment of patient stress, social support, and physical health but not with more objective measures of these variables. When compared with telephone interview diagnosis, the sensitivity and specificity of the CES-D scores were relatively poor, suggesting that the CES-D is not useful as a screening tool for unselected populations. Finally, we found that family physicians base their assessments of depression more on distress than on depressive symptoms. Certain physician myths, barriers, and biases may exist that preclude the effective diagnosis of depression. PMID- 1927589 TI - The best ideal in family practice. PMID- 1927588 TI - The prevalence of selected chronic diseases among the Mexican-American elderly: data from the 1982-1984 Hispanic Health and Nutrition Examination Survey. AB - Although the Mexican-American elderly represent a large and rapidly growing subgroup of the ethnic aged, national prevalence data of major chronic diseases among this population are sparse. Data based on physical examinations from three older groups of the southwestern portion of the 1982-1984 Hispanic Health and Nutrition Examination Survey (HHANES) were reviewed to determine rates of hypertension, diabetes mellitus, arthritis, and heart disease. The results show a higher prevalence of diabetes and lower prevalence of heart disease and hypertension when compared with the general population, coinciding with data from previous studies. Findings for the prevalence of arthritis varied widely from other studies, however, and proportions were lower than expected. Further research on arthritis in the Mexican-American elderly is necessary to determine whether protective mechanisms that may lead to a lower prevalence of this disease exist in this ethnic subgroup. PMID- 1927590 TI - Preconception health care: a critical task for family physicians. AB - Health care leaders in the United States have recently advised that preconception care be made available to all prospective parents because health in pregnancy depends on health status prior to pregnancy. Prenatal care usually begins after the early critical period of pregnancy has passed, and optimal early prenatal care can be achieved only through preconception care. Family physicians, who are ideally suited to provide this care, can readily integrate it into the routine health maintenance they currently provide for their patients of childbearing age. This review highlights components of the medical, family, and social histories, current health, and physical examination that are important to preconception health. There is good evidence that attention to patients' health needs before conception is related to improved perinatal outcomes. PMID- 1927591 TI - Preoperative evaluation of the elderly. AB - As the population ages, an increasing number of elderly patients will need surgery. An organized medical evaluation that focuses on the patient's cardiopulmonary and nutritional status should be performed before the patient undergoes surgery. The initial history and physical examination should be performed up to 8 weeks before surgery. Follow-up examinations are then dictated by the results of the initial examination. Established guidelines to assess cardiopulmonary and nutritional status should be followed. Preoperative laboratory assessment should consist of hemoglobin and creatinine measurements and include a urinalysis and electrocardiogram. The need for additional tests is indicated by the history and physical examination. Following this assessment, therapeutic and prophylactic measures to reduce surgical morbidity and mortality can be implemented. With timely identification and management of medical disease in geriatric surgical patients, the risks of surgery can be minimized. PMID- 1927592 TI - Perinatal testicular torsion. PMID- 1927593 TI - Sinusoidal fetal heart rate pattern after administration of nalbuphine. PMID- 1927594 TI - Squamous cell carcinoma of the ear masquerading as malignant otitis externa. PMID- 1927595 TI - The real enemies: obesity, inactivity, and tobacco consumption. PMID- 1927596 TI - Depression: are we too busy to listen? PMID- 1927598 TI - The need for family medicine in the academic medical center. PMID- 1927597 TI - Low-dose intradermal hepatitis B vaccination. PMID- 1927599 TI - Contraception--natural family planning. PMID- 1927600 TI - Increases of neuron-specific enolase, S-100 protein, creatine kinase and creatine kinase BB isoenzyme in CSF following intraventricular catheter implantation. AB - In 15 patients without acute brain injury the concentrations of Neuron-specific Enolase (NSE), S-100 Protein (S-100), Creatine Kinase (CK), and Creatine Kinase BB isoenzyme (CK-BB) in ventricular cerebrospinal fluid (CSF) were measured immediately after lateral ventricle cannulation for diagnostic or treatment purposes. From patients who were treated with a shunt another CSF sample was obtained one week after shunt implantation by puncture of the antechamber of the valve. The CSF concentrations of NSE, S-100, CK and CK-BB after cannulation were found to be of the same order as found in patients with severe head injury, stroke or subarachnoid haemorrhage. One week after shunt implantation the concentrations of S-100, CK and CK-BB had returned to normal levels in almost all patients, while the NSE concentrations remained elevated. These findings indicate that the sampling procedure may result in contamination of CSF with NSE, S-100, CK and CK-BB and they should be taken into account in the prognostic evaluation of enzyme concentrations after brain injury. PMID- 1927601 TI - Parapontine epidermoid tumours presenting as trigeminal neuralgias: anatomical findings and operative results. AB - Four cases of medically intractable trigeminal neuralgia caused by parapontine epidermoid tumours are reported. All patients presented with typical trigeminal neuralgia and low-density area in the parapontine region on CT-scans. Neurologically in all cases slight hypaesthesia in various divisions of the trigeminal nerve without other neurological signs was revealed. Trigeminal pain was completely relieved after surgery in all patients. Facial sensory disturbances and pain occur in patients with parapontine epidermoid tumour as a result of direct tumourous compression (and hypothetically toxic effects on the nerve root from the tumourous contents). PMID- 1927602 TI - Cystic acoustic schwannomas. AB - Three cases with large space-occupying cysts in the cerebellopontine angle are reported. CT and MRI findings were not typical for acoustic schwannomas but at operation, besides the large cysts, small acoustic schwannomas could be detected and removed. The clinical and neuroradiological features of this unusual variety and the CT and MRI differential diagnosis of cerebellopontine angle lesions are discussed. PMID- 1927603 TI - Intracranial lipomas. AB - Intracranial lipomas are very rare, probably congenital lesions. Though they can occur anywhere in the intracranial space, a good proportion of cases tend to be located around the midline. Review of the literature as well as our own three cases--which forms the basis of this article--shows that they are mostly asymptomatic. When symptoms occur, they are frequently the result of coexisting general clinical conditions. Lipomas used to be reported mainly as incidental findings at autopsy. Advances in neuro-imaging techniques have vastly improved the likelihood of their being discovered during life. At present however, significant increase in the reported incidence of these tumours is yet to be seen. Surgical extirpation of the tumour is not considered necessary in the majority of patients, many of whom show remarkable clinical improvement following shunt procedures for obstructive hydrocephalus as well as treatment of coexisting conditions such as epilepsy. PMID- 1927604 TI - Meningiomas with haemorrhagic onset. AB - Classically meningiomas present and evolve with a progressive course. Meningiomas manifest themselves mainly in middle and old age when the incidence of strokes is higher. The authors report three instances of meningioma with acute haemorrhagic onset. The clinical picture of our cases consisted of subarachnoid bleeding, subdural hematoma and intracerebral haemorrhage respectively. The diagnostic difficulties encountered when assessing these patients are discussed. The current literature regarding meningioma associated with haemorrhage is reviewed. One of our cases seems to be the first reported case of subarachnoid haemorrhage originating from a meningioma of the petrous bone. PMID- 1927605 TI - Intracranial meningiomas associated with glial tumours: a review based on 54 selected literature cases from the literature and 3 additional personal cases. AB - The simultaneous occurrence of meningioma and glioma is extremely rare. Three new cases and 54 adequately described in the literature are analyzed. Clinical diagnosis may be difficult due to discrepancy between clinical and radiological findings. Unexpected clinical deterioration following removal of a tumour and relapse simulating recurrence may occur. The introduction of CT technology does not seem to have offered the expected contribution to the early diagnosis of these coincidental lesions, at least before the introduction of the newer generation scanners or MRI. While removal of both tumours in one session yielded the best results, surgery for the sole glioma appeared to be associated with an unacceptably high mortality. Although several aetiopathogenetic hypotheses have been suggested for explaining this curious association, coincidental meningioma and glioma are most likely to be different primary brain tumours occurring randomly in the same individual. PMID- 1927606 TI - Intraventricular cavernous angioma. A survey. AB - Since the availability of CT diagnosis 23 cases of intraventricular cavernous angioma (IVCA) have been published in the literature. Three additional cases have been operated upon in our Department. Based on these 26 cases the clinical data, radiological findings, treatment and outcome of IVCAs are reviewed. PMID- 1927607 TI - Mechanism of mutism following the transcallosal approach to the ventricles. AB - Transient mutism has been known as a common manifestation following callosotomy for medically intractable epilepsy, but its cause has not been clearly elucidated. In this paper, we report three cases of mutism following a transcallosal approach to tumours in the lateral and third ventricles and retrospectively analyze the surgical, neurological and radiological features which may suggest the cause of this type of mutism. Mutism may be a result of division of the corpus callosum. Suppression of the limbic system caused by lesions in the anterior cingulate gyrus, septum pellucidum, and fornix may have been of importance in at least two of these three cases. Impairments of the supplementary motor cortex, thalamus and basal ganglia may also be factors reducing speech production. The mechanism of such transient mutism seems to be a complex of two or more of these factors, and their combinations may be different from one case to the other. PMID- 1927608 TI - "Isthmic" spondylolisthesis--an analysis of the clinical and radiological presentation in relation to intraoperative findings and surgical results in 72 consecutive cases. AB - 72 patients with isthmic spondylolisthesis have been analyzed prospectively with respect to their clinical presentation, radiological and intraoperative findings, operative techniques and surgical results. Excellent, good and satisfactory results have been obtained in 59 (82%), 10 (14%) and 3 patients (4%), respectively, by use of microsurgical techniques in combination with Louis-plate fixation in Grade I and double arthrodesis/Cotrel-Dubousset-instrumentation in Grade II spondylolisthesis. PMID- 1927609 TI - Intradural disc herniations pathogenesis, clinical picture, diagnosis and treatment. AB - The relatively rare occurrence and uncertainty about pathogenesis of intradurally displaced disc herniations stimulated an anatomico-pathological study into intradural disc herniations. The relation between the ventral dura and posterior longitudinal ligament in the cervical, thoracic, lumbar and sacral regions were examined macroscopically and microscopically, and ventral and dorsal dural thickness was compared in 20 adult autopsies on patients who died from various causes; in addition, 20 late abortions and newborn cadavers were investigated in the same way. In this study, a total of 40 autopsies has shown that the ventral dura is most frequently and firmly attached to the posterior longitudinal ligament at the L4-L5 level and these adhesions may be congenital. In the adult cadavers dorsal dura was found to be thicker than the ventral dura in the lumbar and lower cervical interspaces. Three personal clinical cases of intradurally herniated disc prolapse are shortly described and the diagnosis and management of this pathology discussed. PMID- 1927610 TI - Intraspinal baclofen in the treatment of severe spasticity and spasms. AB - Ten patients with severe spasticity were evaluated according to a standardized protocol in order to be treated by intraspinal baclofen. Entry criteria in the protocol were the following: 1) Stable central nervous system lesion, 2) Severe spasticity and/or flexo-extensor spasms not controllable by oral treatment, 3) Normal CSF circulation and 4) Informed consent. All patients received a test dose of twenty-five micrograms of baclofen injected intrathecally. At intervals of at least one day, doses were increased in 10-25 microgram steps until total abolition of spontaneous spasms was achieved in complete spinal cord lesions. In patients with residual motor function, doses were titrated until the optimal dose was found that reduced spasms and enabled performance of maximum daily life activities according to the patient's neurological level. In nine patients a multidose reservoir was implanted to deliver intrathecal baclofen. Effective dosage was 60 +/- 31 micrograms in the entire group. Ashworth score was reduced from 4.6 +/- 0.7 to 1.2 +/- 0.4 (mean +/- SD) (p less than 0.0001) and spasms from 3.2 +/- 0.8 to 0.2 +/- 0.4 (p less than 0.0001). Follow-up of the nine patients in whom a reservoir was implanted has been 18 +/- 9 months. Initial dosage requirements and tolerance were significantly different in complete (Frankel's A grade) or incomplete lesions (Frankel's B, C and D grades). Complete spinal cord lesions required a greater initial dose (156 +/- 43) than incomplete lesions (44 +/- 24), these differences being statistically significant (Student's t-test, p less than 0.05). Tolerance was observed only in patients with complete motor and complete sensory lesions. In incomplete lesions, dose increase was insignificant. PMID- 1927611 TI - Influence of dopamine on cerebral blood flow, and metabolism for oxygen and glucose under barbiturate administration in cats. AB - The effect of dopamine during barbiturate therapy was investigated in 29 cats including 5 sham-operated cats. According to Kiersey's classification of electro encephalographic patterns, physiological variables, cerebral metabolic rates for oxygen and glucose, cerebral blood flow (CBF), and intracranial pressure (ICP), etc. were evaluated in each electro-encephalographic pattern. Oxygen-glucose index was calculated and used as an indicator for aerobic or anaerobic metabolism of glucose. Group 1 (12 cats), to which only thiamylal was administered, maintained aerobic glycolysis due to a parallel reduction of cerebral metabolic rates for oxygen and glucose (about half of the initial value at Kiersey's fifth pattern) in spite of reduction of CBF and mean arterial blood pressure (MABP). Group 2 (12 cats), to which dopamine was administered in addition to thiamylal due to a reduction of MABP, showed anaerobic glycolysis though MABP and CBF were maintained. These findings are ascribed to an increase of cerebral metabolic rate for glucose up to 130% of the initial value though cerebral metabolic rate for oxygen decreased down to half of the initial value: The beneficial effect of barbiturate on cerebral metabolism was reduced by use of dopamine. ICP was reduced in both groups. Our result indicates that administration of extracellular fluid may be preferable for treatment of hypotension during barbiturate therapy than dopamine medication. PMID- 1927612 TI - Vasospasm due to massive subarachnoid haemorrhage--a rat model. AB - Although the pathophysiology of chronic cerebral vasospasm following subarachnoid haemorrhage (SAH) is still unclear, it is certain that the amount of subarachnoid blood is predictive of the severity of cerebral vasospasm. Accordingly, massive subarachnoid haemorrhage (greater than 0.5 ml) was induced in adult rats via direct injection into the cisterna magna. Compared to other previously published models of experimental SAH in rats a much larger amount of blood was injected. The basilar artery was exposed 72 hours post subarachnoid haemorrhage and photographed under controlled conditions. The diameter of the artery was assessed by an image analyzer. A 50% reduction in diameter was found in 25 rats subjected to SAH as compared to 9 control rats and 4 rats with intracisternal saline injection. We conclude that when massive subarachnoid haemorrhage is induced, and direct measurements of the basilar artery are made, the rat can be used as a reliable model for investigation of SAH induced arterial vasospasm. PMID- 1927613 TI - The effects of HA1077 on the cerebral circulation after subarachnoid haemorrhage in dogs. AB - We examined the effects of the recently developed calcium antagonist HA1077 on cerebral haemodynamics during the chronic stage of the two-haemorrhage canine model system of vasospasm. Regional cerebral blood flow (rCBF), regional cerebral blood velocity and regional cerebral blood volume in the canine parietal cortex were measured by Laser-doppler flowmeter. On the 7th day after the initial injection of autogenous blood, subarachnoid haemorrhage (SAH) produced a significant decrease in rCBF (59% of control, p less than 0.05) and blood velocity (48% of control, p less than 0.05) with no remarkable change in blood volume (108% of control). Bolus intravenous administration of HA1077 (0.1-0.3 mg/kg) dose-dependently increased the rCBF and blood velocity, without significantly changing the blood volume on Day 7 after SAH. HA1077 improves haemodynamic function manifested by an increase in rCBF and velocity in this SAH model, and may be suitable for the treatment of vasospasm in patients with SAH. PMID- 1927615 TI - Successful treatment of a haemangioblastoma in a 95 year-old patient. Case report. AB - Haemangioblastomas located in the posterior fossa have rarely been described in patients older than 60 years of age. The authors report a case of a 95 year-old man who presented with an obstructive hydrocephalus secondary to a posterior fossa tumour. Computed tomography and angiography suggested intracerebellar metastasis. Despite the advanced age of the patient and his poor general condition, surgery was performed with the patient in a supine position. A haemiangioblastoma was found and completely removed. The postoperative course was without complications. This case demonstrates that the combination of modern anaesthesia, supine operating position, and the use of microsurgical techniques allow successful operations on the posterior fossa even in very old patients. PMID- 1927614 TI - Germinoma in a 16-month old baby: a case report with brief review of the literature. PMID- 1927616 TI - A trial of the effect of nimodipine on outcome after head injury. AB - We performed a randomised prospective double blind trial to study the effect of the calcium antagonist nimodipine on the outcome of head injured patients. The subjects were not obeying commands at the time of entry to the study, within 24 hours of injury. One hundred and seventy-five patients received nimodipine IV, 2 mg per hour for up to 7 days and 176 received placebo. The two groups were well matched for important prognostic features. Six months after injury 93 (53%) of the nimodipine group and 86 (49%) of the control group had a favourable outcome (moderate/good recovery). The relative increase in favourable outcomes (8%) was not significant but is compatible (95% C.I.) with an increase in favourable outcomes in treated patients by 33% or a decrease by 12%. Nimodipine was well tolerated and there were few adverse reactions; means of systolic and diastolic blood pressures and the intracranial pressure did not differ between the groups. It is unlikely that nimodipine has a marked effect on outcome (ie an increase in favourable outcome of greater than 15%) after head injury of this severity but the study does not exclude a modest but clinically useful benefit. PMID- 1927617 TI - Concomitant cranio-cerebral and vertebro-medullary injuries. Analysis of 121 cases. AB - The authors report 121 cases of concomitant cranio-cerebral and vertebro medullary injuries observed during a period of eight years. The vertebral trauma was cervical in 59 cases, thoracic T2-T9 in 27, thoraco-lumbar T10-L2 in 30 and lumbo-sacral in 5. Surgical treatment for both cranio-cerebral and vertebro medullary injury was performed in 6 cases, for the cranio-cerebral lesion only in 27, for the vertebro-medullary one only in 25. The remaining cases had both lesions treated conservatively. Although concomitant cranio-cerebral and vertebro medullary traumas are considered not uncommon, large series of cases are scanty. The peculiar diagnostic and therapeutic problems that this association of injuries poses are discussed. Long term results are analyzed as well. PMID- 1927618 TI - Neurological deficit in injuries of the thoracic and lumbar spine. A consecutive series of 70 patients. AB - Seventy consecutive patients with injuries of the thoracic and lumbar spine accompanied by neurological deficit were prospectively studied and follow-up. In 40 of these patients with a burst fracture, the degree of involvement of the cross-sectional area of the spinal canal, as revealed on first CT after admission, was not correlated with the type and degree of initial neurological deficit. In patients with injuries of the lumbar spine, neurological deficit may be mild, although the sagittal diameter of the spinal canal may be reduced by as much as 90%. We cannot establish a difference in neurological recovery between those cases who were managed conservatively and those in whom a surgical decompression and stabilization procedure was performed. Surgical stabilizing procedures, however, result in immediate stabilization of the spine, they diminish pain, facilitate nursing care and allow more rapid mobilization and earlier active rehabilitation. If major extraspinal injuries form a relative contra-indication to surgical decompression of the cord and stabilization of the spine injury, the patient can quite well be treated conservatively without endangering neurological recovery. PMID- 1927619 TI - Surgical treatment of extradural spinal cord compression due to metastatic tumours. AB - The authors present a group of 23 patients with extradural spinal metastases who had undergone surgical treatment with different approaches, with reference to the anatomical site of the tumours. They report the results and discuss the criteria of the different surgical technical choices. PMID- 1927620 TI - Surgical approaches to thoracic disc herniations. AB - Early diagnosis of thoracic disc herniations has become more common with the advent of spinal magnetic resonance imaging (MRI). This early diagnosis combined with choosing the optimal surgical approach, to ensure adequate decompression without excessive cord and root manipulation, will achieve the optimum results. It is now clear that more lateral and anterior approaches to the thoracic spine are required to achieve this goal. We report our experience in the operative management of 21 patients with thoracic disc herniation using three different surgical approaches: transpedicular-transfacetal, posterolateral-extrapleural (costotransversectomy) and transthoracic-transpleural. The clinical and radiologic findings and results in all of our cases are reviewed as are the technique of and indication for each of the three surgical approaches. PMID- 1927621 TI - Clinico-morphological correlation in syringomyelia: a statistical study assisted by computer measurement of magnetic resonance images. AB - A computer-assisted measurement of synrinxes was performed on MR images in a series of 26 patients with syringomyelia-Chiari complex. Syrinx data such as length, surface area, contour, and greater diameter were statistically correlated to each other and with the main clinical symptomatology of the patients. In general, a direct relationship between the various measurements of the syrinxes exists. Nevertheless, although a slight relationship could be established between the presence of muscular atrophy and a greater length and contour of the syrinxes, the present study suggests that the evaluation of syrinx dimensions cannot be brought into relation with the nature or distribution of clinical symptomatology. Because a reduction in the syrinx is generally the aim of surgery, this conclusion should be born in mind when a surgical treatment is offered to syringomyelic patients. PMID- 1927622 TI - Spontaneous spinal epidural haematomas. AB - The spontaneous spinal epidural haematoma (SSEH) is a rarity, but the severe and permanent motor disability underlines its importance. From 1957 seven cases of SSEH have been diagnosed and operated on in the National Institute of Neurosurgery, Budapest. These cases are analysed and discussed. The clinical picture began with local pain of the spine and radicular signs but some hours or days later paraparesis or paraplegia and incontinence developed. In the discussed cases the neurological deficit progressed to complete para- or tetraplegia in 5 cases. Only 2 patients had partial spinal transverse lesions on admission. All patients underwent myelography to detect the spinal space occupying lesion and were operated on soon. Three patients recovered completely, 2 remained partly and 2 totally paralysed. The outcome depended mainly on the timing of neurological deficiency. If the neurological signs existed less than 8 hours the patients recovered completely or fairly well while the prognosis was poor if the transverse lesion persisted longer than 24 hours. The authors stress the importance of correct and fast decisions at the first medical examination for the outcome of this disease, because only immediate transfer to a neurosurgical department gives a chance of good recovery. PMID- 1927623 TI - Spinal cord stimulation and cerebral haemodynamics. AB - An increase of regional cerebral blood flow (rCBF) has been shown to occur in man during spinal cord stimulation (SCS) by Hosobuchi (1986) and by Meglio et al. (1988) using the 133-Xenon wash-out technique. In this paper we report the effects of SCS on CBF as measured by two different techniques: 8 patients were studied with the 133-Xe method and 28 with the transcranial doppler sonography (TCD), in two cases both studies were performed. The aim of our study was to: 1 verify the effect of SCS on CBF, 2-compare observations made by two different methods, and 3-evaluate a possible correlation between the stimulated spinal segmental level and the modification of CBF. The results of our study confirm that SCS interacts with the mechanisms of regulation of CBF. The stimulation of different spinal cord levels in the same patient can produce different effects and such effects are reproducible. An increase of CBF is more likely to occur with the stimulation of the cervical spinal cord. In patients studied by both methods the sign of CBF changes induced by SCS was the same. Finally, in two patients the effect of SCS on CO2 autoregulation was studied with TCD. The results of such a study, although preliminary, suggest that CO2 and SCS have a competitive effect upon the mechanisms of regulation of CBF. PMID- 1927624 TI - The acute effect of nimodipine on cerebral blood flow, its CO2 reactivity, and cerebral oxygen metabolism in human volunteers. AB - The present study was undertaken in 8 healthy volunteers to examine the effect of a clinically relevant dose of nimodipine (NIM) (15 and 30 microgram/kg/h) on CBF, its CO2 reactivity, and CMRO2. Mean arterial blood pressure (MABP) was measured intra-arterially. Regional CBF was measured by SPECT of inhaled Xenon-133. During the CO2 reactivity tests changes in CBF were estimated by the arterio-venous oxygen-difference method. Median CBF was 52 ml/100 g/min (48-53) with a normal regional distribution, and median baseline MABP was 96 mmHg (92-99). MABP was slightly reduced, by 8 mmHg (7-9), and 9 mmHg (4-11) after infusion of NIM for 2 and 4 hours, respectively. CBF, however, remained constant, although correction for changes in PaCO2, revealed a slight increase after 4 hours (p = 0.08). CMRO2 was 3.5 ml/100g/min (3.2-3.5) and was not changed by the infusion of NIM. At arterial CO2 tensions ranging from 4.0 to 6.5 Kpa the CO2 reactivity was 3.0% CBF/0.1 kPa (2.6-3.7) and decreased significantly to 2.6% CBF/0.1 kPa (1.8-3.2) after the infusion of NIM for 3 hours (p = 0.02). The median slope of the LnCBFsat/PaCO2 relationship was 1.5 at baseline compared to 1.3 after NIM (p less than 0.01). No side effects were observed. The present study shows a decreased CO2 of the cerebral vessels and a maintained coupling of CBF and CMRO2 during the infusion of nimodipine. PMID- 1927626 TI - Development of the operating computerized tomographic scanner system for neurosurgery. AB - A computerized tomographic (CT) scanner system for intraoperative imaging is presented. The system consists of the following: 1) CT scanner with a mobile gantry, 2) digitally controlled operating table with central processing unit (CPU) and encoder unit; the table can be controlled by the scanner computer as accurately as the scanner bed, and 3) exclusively designed head fixation devices. It allows us to scan the patient on the operating table in the operating room pre operatively, intra-operatively and immediately after surgery. PMID- 1927625 TI - Leucocyte depletion does not affect post-ischaemic nerve cell damage in the rat. AB - Leucocytes play an important role in inflammation and immunologic responses. They might be of special significance under pathophysiological conditions of the brain i.e. ischaemia or stroke. It has been shown that neutropenic animals undergoing reversible ischaemia show higher post-ischaemic blood flow, suggesting improved post-ischaemic perfusion. In this study it was investigated therefore, whether polymorphonuclear leucocytes contribute to the nerve cell loss in the hippocampus after a reversible period of ischaemia. Rats were made neutropenic with a specific anti-serum against rat polymorphonuclear leucocytes yielding leucocyte counts less than 10% of normal. The animals were then subjected to 15 min reversible forebrain ischaemia. Quantitative histology was performed after a survival period of 7 days. Nerve cell counts in the frontal cortex and in the CA1 and CA3 sectors of the hippocampus did not reveal any differences between neutropenic rats and animals with normal leucocyte counts. From the results it might be concluded that neutrophils do not significantly contribute to the selective post-ischaemic nerve cell damage in the rat. PMID- 1927627 TI - Technical improvements in the lateral suboccipital approach for neurovascular decompression of the trigeminal and facial nerves. AB - Some refinements of the surgical procedure are described in 12 patients (five females, seven males) operated on for neurovascular decompression (ND) in the presence of trigeminal neuralgia and hemifacial spasm. The patients were operated upon in the supine position, in which the use of a lumbar drainage facilitates the dissection from the beginning. The lateral suboccipital approach was performed by means of a semi-osteoplastic craniotomy with the use of bone chips to close the bone defects so that a good cosmetic effect could be achieved. PMID- 1927628 TI - Patients with moyamoya disease who had not fully benefited from encephaloduro arterio-synangiosis (EDAS) PMID- 1927629 TI - Identification and partial purification of a GM1-binding protein from presynaptic vesicles. AB - Synaptic vesicles purified from rat forebrain contain a protein with membrane binding activity. The binding has a high degree of selectivity for sialoglycosphingolipids. The protein was partially purified by affinity chromatography on lysoGM1 silica beads. The protein bands thus isolated have an apparent Mr of 65 and 53 KDa respectively. PMID- 1927630 TI - Epidemiological and clinical features of primary intrarachidian tumours in the island of Sardinia, during the 1977-1986 period. AB - The cases of primary intrarachidian tumours observed in the 1977-1986 period in the neurological, neurosurgical, oncological and radiological Departments in Sardinia, were collected. Only histologically diagnosed tumours of spinal cord, root-nerve and their envelops in patients resident in the island for at least one year were included in the investigation. The annual crude incidence rate was 0.5 per 100,000 population (0.63 in the females and 0.37 in the males). M/F ratio was 1.7. Mean age was 45 years (35.5 in males; 50.7 in females). Age and sex distribution showed higher frequence of intrarachidian tumours in females over 40 years of age and in males younger than 40 years. Meningiomas were more frequent in females aged between 47 and 74 years. The dorsal localization of the tumours was more frequent. Subjective sensory complaints (85.3%) and motor impairment (76%) were the main symptoms at onset; at the time of diagnosis motor impairment (92%) and objective sensory disturbances (82.7%) prevailed. A twelve months interval elapsed between onset of first symptoms and diagnosis in 64% of patients; within 24 months 81.3% of tumours were diagnosed. Surgery induced improvement in 74.6% of patients, no improvement in 17.3%; a worsening was noticed in 8%. Seven patients died after surgery (3 owing to the tumour). These data are partly consonant and partly in contrast with those present in literature. PMID- 1927631 TI - Multimodal evoked potentials in diabetics. AB - In the present study we performed brainstem auditory evoked potentials, pattern electroretinogram and visual evoked potentials for the identification of a subclinical involvement of central auditory and visual pathways in diabetes mellitus. We tested 30 patients, and a neurophysiological central nervous system involvement was demonstrated in 23.3% of them. The mean values of patients and controls were significantly different for most of the evoked potential parameters. Some of these parameters were linearly related with duration of the disease, clinical score and peripheral nerve conduction velocities. PMID- 1927632 TI - Multiple sclerosis in childhood. Longitudinal study in 14 cases. AB - The Authors review the literature on the occurrence of multiple sclerosis in children and add 14 personal cases below the age of 15.5 years, the youngest being 6.4 years old. Modality of onset, clinical course, clinical classification according to the criteria proposed by McDonald and Halliday, paraclinical evidence of lesions and disability grade at the last control are widely discussed. Eleven cases were scheduled as clinically definite multiple sclerosis. In the youngest children the recovery may be often complete or the disability grade may be low. PMID- 1927634 TI - An adjustment method for spinal cord stimulators based on simplified gait analysis (1). AB - The use of electrical stimulators, for pain relief, spasticity reduction, and other applications, is greatly increasing; the programming facilities of the new devices extend the application range and allow to reduce the manufacturing costs. On the other side it is necessary to define methodologies and protocols for a custom setting of these devices. This work, although for only one patient, is a proposal for a methodology, based on a simplified gait analysis, for the adjustment of a spinal cord electrical stimulator. PMID- 1927633 TI - Atrial fibrillation and infarct area extent in ischemic stroke. A clinical and neuroradiological study in 104 patients. AB - The extent of infarct area (IA) on CT-scan in 104 patients with ischemic stroke (IS) was compared with the presence of atrial fibrillation (AF) and other risk factors (hypertension, dyslipidemia, alcohol abuse). Infarct size was also compared with biological and clinical parameters in acute stage (6-12 h) (blood glucose level, systolic and diastolic arterial pressure, haematocrit, consciousness, clinical picture) and with clinical outcome. Among risk factors, only AF showed a significant correlation with IA extension (p less than .0009). IA correlated also with consciousness (p = .0017), clinical picture (p = .0145) and with clinical outcome (p less than 10(-6). Patients with AF showed a more severe clinical outcome with respect to patients without risk factors. It could be hypothesized that patients with AF have a reduced capacity for increasing or sustaining cerebral blood flow in the acute phase of IS. PMID- 1927636 TI - Cocaine induced hypertensive encephalopathy. AB - A 40 year old chronic cocaine abuser came to hospital with a blood pressure of 260/160, headache, agitation and bilateral papilledema. She was felt to have hypertensive encephalopathy secondary to cocaine abuse. She failed to respond to initial treatment with intravenous nitroprusside alone but was responsive to additional therapy with captopril. PMID- 1927635 TI - Narcolepsy and psychopathology. A case report. AB - The case of a 14-year-old girl presenting with the association of a clearcut narcoleptic syndrome and psychiatric disturbances is reported. Tricyclic anti depressant drugs and hypnagogic hallucinations seem to play a precipitating role on delusional episodes in a predisposed subject with a positive psychiatric familial history. PMID- 1927638 TI - [Recurrences and new occurrences]. PMID- 1927637 TI - Single photon emission computed tomography with 99mTc-HMPAO in HIV-1 infection: a help in early diagnosis of AIDS dementia complex. PMID- 1927639 TI - [Infiltrating transitional cancer of the bladder (2). Prognostic value of the stage. Its influence on the therapeutic decision)]. AB - The only reliable sign to give a prognosis is the anatomopathological stage (P or pT) obtained from the study of the cystectomy surgical piece: partial or total. Tumourless (P0) bladders conceal the inability to reach any certainty over the tumour's inexistance. Removal should not be considered as a success but an error. The fact that no tumour is found in the removed bladder does not guarantee that the patient will not eventually die of metastasis. A pT2 stage has a better prognosis than pT3a and both evolve better that either pT3b or pT4a and, therefore, their treatment and management may be different. Clinical stage (T) is not a reliable sign: the possibilities of over and undervaluation are very high. Subtraction of P from T cannot be maintained as an adequate sign to assess the action of the adjuvant therapy to surgery and should be excluded in order to delimit the action of the neo-adjuvant chemotherapy. Also, patients with pT2 and pT3a tumours should be excluded from these protocols since the possibilities that they may be removed during the evaluation R.T.U. are high. PMID- 1927640 TI - [Hypertrophy of Bertin's columns]. AB - Description of 17 cases of columns of Bertin's hypertrophy found by chance while performing 587 urological ecographies carried out while following other urogenital diagnostic approaches. The present report is prompted by the entity's features and the differential diagnosis forced by the "renal mass effects". A series of reflections are built on the various supplementary tests that can be performed. PMID- 1927641 TI - [Diagnosis of the composition of urinary calculi based on ions study in blood and urine]. AB - Description of a diagnostic procedure by presumption of urinary calculi composition, based on the comparative statistical study of a group of blood and urine ions which have allowed identification of such composition, with little margin of error, in 264 renal calculi prior to complete fragmentation by extracorporeal lithotrity with pressure waves, and for which it was possible to choose the most suitable cycle and intensity. PMID- 1927642 TI - [Surgical renal biopsies: technique, effectiveness and complications]. AB - Retrospective study made on 140 renal surgical biopsies (RSB) performed throughout the past 4 years in our Unit. The technique's effectiveness and morbidity are emphasized and the surgical technique and type of anaesthesia described. The sample obtained was enough to perform an essay in 100% cases, and a diagnosis was reached in 98.5%. Thirty-nine patients (27.8%) presented complications, 13 (9.2%) of which were directly related to the surgical technique. No case required blood transfusion and no deaths were reported. The type of anaesthesia used was: local plus sedation in 104 (74.2%) cases, rachianaesthesia in 10 (7.1%) and general in 26 (18.5%). The same approach was used in all patients: minimal subcostal lumbotomy, using Wilde's forceps to obtain the samples. It is believed that RSB is a highly effective, low mortality procedure, easy and quick to perform, and suitable for selected patients. PMID- 1927643 TI - [Selective use of IVU in acute pyelonephritis in adults]. PMID- 1927644 TI - [Survival analysis in renal cell carcinoma with invasion of the vena cava]. AB - Ninety-nine consecutive patients with renal cell carcinoma in stages pT1-4/N0 3/V0-2/M0 were analyzed. Overall 5 year survival was 61%. Factors with greater impact on survival were: 1) degree of anaplasia (DI 73%, DII 47%, DIII 27%; p = 0.0005), 2) pathological stage (pT1-2 87%, pT3 39%; p = 0.0000), 3) perirenal fat invasion (pT1-2 87%, pT3a 60%; p = 0.007), 4) node status (N0 72%, N1-3 17%; p = 0.0000) and 5) veins invasion (V0 74%, V1-2 35%; p = 0.005). No difference in survival between V1 and V2 (40% vs 33%; p0.05) tumours was found. A multivariable study showed that the degree of anaplasia and veins invasion have a significant and separate influence on survival (p = 0.0000). Among patients with vascular invasion, those with no perirenal fat invasion or node damage show better survival rates than patients with capsular infiltration (62% vs 40%; p) and perform significantly better than patients with capsular invasion and nodal implication (62% vs 30%; p). No survival differences were observed between pT3b stages with venous invasion only and pT1-2 stages (p0.05). Venous invasion is not in itself of prognostic relevance; the prognostic significance of vascular invasion is directly related to the presence of perirenal fat invasion and/or nodal implication. PMID- 1927645 TI - [Spanish urology in the renaissance]. AB - Spanish renaissance urology is a heirloom from both islamic and scholastic medieval trends. Theory and practice of urology generates three types of professionals: doctors, who study at universities and obtain their licence by making a demonstration before the Protomedicato Tribunal; surgeons, who acquire their surgical techniques through a teacher-pupil training relationship outside universities; and empirics, who were in charge of performing surgical operations. Urology literature exhibits greater interest during the second half of the century. Most outstanding are the works of Francisco Diaz. The pathologies arising greater interest are lithiasis and carnosities. Lithiasis is handled by lithotomists through a carving process of which there were two modalities, castilian and italian. Carnosities, which differential diagnosis, as well as that of lithiasis, was outlined by Andres Laguna, are treated using a dilating bougie or, surgically, with a sharp instrument analogous to the urethrotome devised by Francisco Diaz. PMID- 1927646 TI - [Papillo-polypoid cystitis. Focal cystitis with pseudoneoplastic aspect]. AB - Report on 12 patients with vesical papillary changes of the mucosa, endoscopically assessed as tumours, but where the pathological study showed to be no epithelial neoplastic changes, since exophitical growth was a consequence of the submucosal edema (91.6%) with a moderate inflammatory reaction. Twenty-five percent cases exhibited no causative factors and 75% were correlated to urethral catheter (average 2.3 months). Due to major the and microscopic similitude between low degree transitional cell carcinoma and the localized inflammatory changes (papillary cystitis) the criteria to establish a correct diagnosis are discussed. PMID- 1927647 TI - [Paratesticular rhabdomyosarcoma]. AB - Report of one paratesticular RMS in a 28 year-old male. The paper includes a review of the various clinical, etiopathogenic and therapeutic features involved. RMS is a neoplasia difficult to diagnose through M.O. and, quite often, it is necessary to use immunohistochemical techniques in order to discover some of the muscular fibre markers, such as Desmin, Myosin and Myoglobin. Several theories have been put forward to explain its origin, and the most widely accepted defends an origin in a poorly differentiated mesenchymal tissue. The advantages of retroperitoneal lymphadenectomy following orchiectomy are discussed as treatment. PMID- 1927648 TI - [Epithelial polyp of the posterior urethra]. AB - A case of posterior urethra polyp located at the veru montanum is reported in an adult with azoospermia. Deferentvesiculography, testes biopsy, transrectal echography and urethroscopy were carried out. Following diagnosis, a tumour endoscopic resection was performed. After reviewing the literature, no other cases of posterior urethra polyp presenting the reported clinical picture was found. Also, aspects related to clinic, diagnostic procedures and therapeutical approach are reported. PMID- 1927649 TI - [Bladder adenocarcinoma of urachal origin. A rare tumor]. AB - With the description of this new case of urachal adenocarcinoma in the vesical cupula we provide a review on the clinical, pathological and immunohistochemical aspects of this rare tumour, as well as a diagnostic and therapeutical approach. Its subepithelial infiltrant nature delays discovery and denotes both an insidious evolution and poor prognosis. Mucinoid production, nodes pattern and certain immunohistochemical substances as well as abnormalities in the cell's DNA content are attributes of this entity. Only surgery, either partial or exeresis, is effective since this is a radioresistant and dubiously chemosensitive tumour. PMID- 1927650 TI - [Metastasis in the glans of prostatic adenocarcinoma. Apropos of a case]. AB - Case of an 83 year-old male with metastatic penis cancer located at the glans, secondary to moderately differentiated prostatic adenocarcinoma. There was early metastasis clinically expressed as several painful and ulcerous nodes at the glans corona and paraphimosis. The clinical rareness of metastasis in a porous body (glans) as opposed to the more frequent cavernous ones is outlined. Diagnosis was made through biopsy. Treatment is complex since neither radiotherapy, chemotherapy or hormonal-therapy appear to be effective. Occasionally, in the event of solitary nodes partial penectomy should be indicated. Usually, the only feasible treatment is palliative. Presence of such type of metastasis should always be considered as a sign of poor prognosis. PMID- 1927651 TI - [Fibroepithelial polyp with atypical stromal cells in the trigone of the bladder as a cause of lower obstructive uropathy]. AB - Fibroepithelial polyp of the trigone of bladder conditioning an occlusive syndrome at the bladder cervix level causing secondary multidiverticular bladder with ureterohydro-nephrosis and chronic bilateral pyelonephritis. Besides the rare vesical location for the fibroepithelial polyps, the case also presents some atypical stromal cells. PMID- 1927652 TI - [Abscess of the prostate: intracavitary echography and echo-guided drainage]. AB - We submit the present paper three cases of prostate abscess. The various aspects related to ethiopathogeny, clinic, and current diagnostic procedures are analyzed emphasixing the use of endocavitary echography, as well as the different therapeutic approaches that can be used, with particular attention to ecomonitored aspirative drainage. PMID- 1927653 TI - [Epidermoid carcinoma of the penis]. AB - Four cases of Penis Epidermoid Carcinoma, three treated with partial amputation and one with Co60 radiotherapy due to the patient's refusal to undergo surgery, are illustrated. After an average follow-up of 14 months (2-24), patients who underwent surgery have not relapsed. Local relapse was observed in the patient given radiotherapy within 6 months. PMID- 1927654 TI - [Hyperammonemia and transient blindness after transurethral resection of the prostate. Review of a case]. AB - We report a case of hyperammonemia and transient blindness following transurethral prostatic resectin. Glicine and ammonia metabolism are reviewed. Water intoxication may not account for these symptoms. PMID- 1927655 TI - [Unilateral essential hematuria: diagnostic and therapeutic attitude in 2 cases]. AB - Unilateral essential haematuria is an unusual clinical entity where diagnosis is achieved by exclusion of other urological and nephrological conditions. The paper reports two female patients with unilateral anaemic macroscopic haematuria which were evaluated using flexible ureteropyeloscopy, and one also underwent percutaneous pyeloscopy. In one of the patients a renal papilla haemangioma was found which was fulgurated, while the lesion was not identified in the other patient, although neither of them has shown haematuria recurrence during the follow-up period. The authors believe that uretororrenoscopy and percutaneous nephroscopy should be considered in selected patients with unilateral essential haematuria due to its diagnostic and therapeutic possibilities. PMID- 1927656 TI - [Recuperation of ureteral peristalsis in the rat after denervation]. AB - The paper presents the experimental work carried out on the influence of various surgical situations on ureteral peristalsis in the rat. It included 43 rats divided in three groups. Group I (n = 10) acted as control group and had only ureterolysis performed. In group II (n = 10), single section and subsequent anastomosis was performed. Group III (n = 23) included section at two levels, ureter extraction from the animal and subsequent autotransplantation of the ureter. The three groups were re-operated two months later to ratify peristalsis of the intervened ureter. Both in the first and second operations peristalsis, as well as the features and appearance of antiperistaltic waves were quantified. After 60 days, no changes were observed in group I, but groups II and III exhibited normal peristalsis to presence of antiperistaltic waves. Both groups had complications like stenosis, fistulas and hydronephrosis, but also normal functioning, histology and peristalsis. PMID- 1927657 TI - Cell proliferation and cytogenesis in the mouse hippocampus. AB - In the present work, processes of cell proliferation, cell death, neurogenesis, and gliogenesis in the mouse hippocampus were studied. The mapping of distribution of hippocampal mitoses and counting of their number allowed a more precise definition of the data concerning the disposition and age reduction of proliferative sites in Ammon's horn and the dentate gyrus in the mouse. As a result, the following generalized scheme of development and age reduction of the germinal zones in the mouse hippocampus has been suggested. 1. Ammon's horn a) The ventricular zone, from the beginning of formation of the hippocampus (E11) until E20 b) The suprafimbrial zone, from E16 until P7 2. Dentate gyrus a) The prime germinal zone ("the anlage of the dentate gyrus" of Stanfield and Cowan1979b), from E15 until P3 b) The proliferative zone of the hilus, from P3 until P14 c) The subgranular zone, from P3 until adult age The adduced scheme needs some comments: 1. In the hippocampus (as well as in other formations of the developing brain), primary precursors of all types of cells of neuroectodermal origin are represented by cells of the ventricular zone. They give rise to cells of secondary germinal zones in the dentate gyrus and Ammon's horn and are direct precursors of the majority (if not of all) neuronal cells in Ammon's horn, the earliest originating generations of neurons in the dentate gyrus, hippocampal radial glial cells, and, evidently, of a considerable part of astroblasts and oligodendroblasts in Ammon's horn. 2. In contrast to the subiculum, Ammon's horn in the mouse lacks a subventricular (subependymal) zone. These data differ from the results obtained in the rat, where the subventricular zone is described both in the subiculum and Ammon's horn (Bayer 1980b) and from the study in the monkey, where the subiculum and Ammon's horn lack the subventricular zone (Nowakowski and Rakic 1981). Thus, in the case of the mouse, the subventricular zone can serve as a cytoarchitectural characteristic allowing detection of a border between the developing subiculum and Ammon's horn. (Another developmental feature which also identifies the border between Ammon's horn and the subiculum is a considerable number of dying cells in the region of the joint of these structures on E20-P3). 3. In the developing dentate gyrus and Ammon's horn, several extraventricular (i.e., located at a distance from brain ventricles) secondary germinal zones exist. Thus, during embryonic and early postnatal periods of the mouse development, the prime germinal zone occupies a larger part of the presumptive dentate gyrus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1927658 TI - Disenfranchised grief: the loss of an adolescent romantic relationship. AB - This paper identifies the conclusion of a romantic relationship as a significant loss for adolescents. The grief response initiated by this loss is frequently disenfranchised by adults and peers. Adolescent grief symptomatology as well as strategies for surviving a loss are outlined. PMID- 1927659 TI - Stability and change in adolescents' positive attitudes toward guidance in moral development. AB - A total of 1,913 junior high school and college students tested between 1978 and 1988 responded to a 15-item questionnaire on the extent and type of influence they thought desirable in developing moral judgment in elementary, secondary, and college students. The average response across subjects, year of administration, and age of individuals for whom the item was being tapped was highest for the influence of the individual him/herself (2.52 on a 3-point scale), but also relatively high for the three institutions tapped: family (2.17), school (1.85), and clergy (1.45). Peers' influence was rated at 1.84. Differences on the other dimensions (year of questionnaire, sex, and age of subject) were rarely substantial, and while yielding some significant differences, did not show clear, strong patterns. PMID- 1927660 TI - Eating concerns on two Christian and two nonsectarian college campuses: a measure of sex and campus differences in attitudes toward eating. AB - Eating concerns among college men and women on two campuses with an explicitly Christian world view and two nonsectarian campuses, each campus in a different section of the country, were examined in three experiments using the Wellesley Eating Attitudes Survey. Chi-square tests indicated that eating concerns were significantly more frequent among women than men, but men showed a surprisingly high degree of concern. Campuses differed in their level of concern. The relative incidence of overweight in the four sections of the country (Northeast, West, Midwest, and South), as measured by the Centers for Disease Control (1989), appeared more closely related to the level of concern at each of the campuses than the presence or absence of an evangelical Christian world view. Recommendations are made for appropriate support services for students with eating concerns at each campus. PMID- 1927661 TI - Drug and alcohol prevention project for sixth graders: first-year findings. AB - Data gathered in this study are the first-year results of a three-year program evaluation for a drug and alcohol prevention project. One hundred fifty-two 6th graders made up the target group which received instruction using Botvin's life skills training curriculum. Sixty-four additional subjects made up a control group which received no treatment. Both groups were pre- and posttested on the following variables: knowledge about and attitudes toward substances, self concept, passivity, and locus of control. Results indicated that the program had a significant positive impact on the target subjects' passivity, knowledge about drugs and alcohol, and self-image. PMID- 1927662 TI - Young people's perception of the space shuttle disaster: case study. AB - To explore how young people were affected by the space shuttle disaster, the responses of 79 females in 5th, 8th, and 12th grades and 18 males in 5th grade who had witnessed the event on video at school were examined. Six days after the Challenger accident, they were asked to list and rank the three things that had affected them most over the last seven days and to explain the reason behind their first choice. Only 8.9% of the females ranked the space shuttle first, and only 30.4% ranked it in the top three. Competing issues were school-related activities, grades, and family relations. Of the 5th-grade males, 88.9% mentioned the space shuttle and 38.9% saw it as their top concern. For both males and females, this choice was based on sadness and empathy. The youths did not relate the disaster to the fragility of modern technology or the threat of nuclear war. The relatively low response rate of the females who had witnessed this event was interpreted as being indicative of repression-denial. It was concluded that future research should address the extent to which post-crisis denial could be masking more significant psychological trauma in youth. PMID- 1927663 TI - Variables associated with success in an adolescent drug treatment program. AB - The purpose of this study was to investigate the variables that predicted success in an adolescent inpatient drug treatment program. The prognosis in 94 adolescent polydrug abusers was determined on the basis of the MMPI, the Millon Adolescent Personality Inventory, Wechsler IQ, and historical variables. Favorable outcome was associated with being female, having fewer legal difficulties, fewer neurological risk factors, less pathological MMPI scores, higher Verbal IQ, and lower Performance IQ. PMID- 1927664 TI - Tom, Huck, and Oliver Stone as advocates in Kohlberg's just community: theory based strategies for moral education. AB - Kohlberg's studies of moral reasoning provide a good theoretical framework for describing the developmental process that may serve as the basis for programs of moral education for adolescents. Kohlberg viewed moral education, particularly during adolescence, as the stimulation of the natural developmental process which leads to mature moral reasoning. Building on Kohlberg's work, specifically his concept of the just community approach where the teacher and more advanced peers serve as advocates of mature moral reasoning, this article presents the educator with a theoretical rationale for implementing procedures that can foster moral development. A case is made for using contemporary films and literature as mechanisms for stimulating moral development among adolescents. PMID- 1927665 TI - The development of adolescent sexual intimacy: implications for counseling. AB - This paper proposes a perspective for understanding the development of adolescent sexual intimacy. A "transitional stage" is described in which adolescents, driven by a variety of developmental needs influenced by external forces such as peers and family, experiment with sexual behaviors. The completion of the transitional stage results in the adolescent's ability to achieve "relational" sexual intimacy, which is also described. The problems and implications for counseling associated with the biophysiological and family dynamic influences on the development of adolescent sexual intimacy are discussed. PMID- 1927666 TI - A multiple regression analysis of family factors affecting the potential for alcoholism in college students. AB - This study explored the effects of the family system on the potential for alcoholism in college students. Analysis of the data indicated that students' gender, race, and how often they consumed alcohol were unrelated to the potential for alcoholism. However, perceived conflict in the students' family of origin appeared to increase the potential for alcoholism. This finding is consistent with family systems theory, used by many human service professionals as a basis for assessing and treating chemical dependency. PMID- 1927667 TI - Revelations of adolescent mothers: an intensive case-study approach. AB - An intensive case-study approach was utilized with a sample of low-income females (19 black, 1 white) enrolled in a program for adolescent mothers. Audiotaped interviews examined self-image, gender role beliefs, relationships, ways of knowing, and future plans. Participants revealed a positive self-image, an association of womanhood with motherhood, an ability to picture themselves in a variety of future roles and relationships, negative attitudes toward men, matriarchal family structures, and subjective ways of knowing. The results were interpreted in the context of identity formation. Limitations included the presence of white interviewers and confounding effects of program participation. The findings have implications for future research in relationship and courtship patterns of the black subculture and the role of motherhood in identity development. PMID- 1927668 TI - The relationship between self-efficacy and depression in adolescents. AB - This study examined the self-efficacy status of depressed versus nondepressed adolescents. As predicted, self-efficacy was negatively correlated with depression. A three-way interaction of Sex x Age x Level of Depression suggested separate analyses for males and females. Regression analysis revealed age-related changes in the dependence of depression scores on general, academic, physical and social self-efficacy status. It was concluded that self-efficacy has an important relationship with adolescent depression. The implications of these findings are discussed. PMID- 1927669 TI - Adolescent dress, Part I: Dress and body markings of psychiatric outpatients and inpatients. AB - This paper investigated the dress and body markings of 100 adolescent psychiatric patients (both hospitalized and never-hospitalized). Data were obtained from in depth interviews conducted by a child psychiatrist. In contrast to nonhospitalized patients, hospitalized patients had a higher incidence of self scarring, i.e., marks applied to self, either as a self-mutilation/suicide gesture or serving another purpose (for example, carving a boyfriend's initials into one's arm). Other individual expressions of appearance did not differentiate hospitalized from nonhospitalized patients. Detailed dress and appearance observations, questionnaires, photo reviews, self-portraits, and family discussions contributed to the beneficial effect of psychotherapy by focusing on feelings evoked and symbolized in dress and body markings. PMID- 1927670 TI - Ecologically based interventions in residential and school facilities: theory or practice? AB - An overriding theme within systemic therapies has been the need for the development of a comprehensive and coordinated network of community-based treatment resources to effectively meet the unique needs of adolescents experiencing emotional difficulties. An ecosystemic approach to meeting this need focuses on the interdependence of such environmental elements as the residential institution, the school, various social agencies, peer group, and the family in the life of the adolescent. Ecological interventions consider the significant environmental elements, the relationships among these elements, and the adolescent's interaction with them. Such an ecosystemic model is essential to planning and implementing academic and social programs for our youth. This paper illustrates some important differences between interdisciplinary and ecological perspectives. It highlights the use of ecosystemic models in residential and school facilities and also enumerates areas where ecologically based changes might be appropriate. In addition, it outlines operational guidelines focusing on the reintegration of the adolescent from the institution back to the neighborhood school. PMID- 1927671 TI - Factors related to cigarette smoking and alcohol use among adolescents. AB - Based on a national survey of Icelandic adolescents, this study examined the various predictors of cigarette smoking and alcohol use. It was found that the use of tobacco and alcohol was related to a number of different factors: sex, residence, hours of paid work, physical activities, social network, educational performance and beliefs, and psychological distress. Further, smoking and drinking had most predictors in common. It was concluded that existing theoretical perspectives on juvenile deviance do not provide an adequate account of adolescent smoking and drinking. The need to integrate existing theories into a wider explanatory framework is discussed. PMID- 1927672 TI - Adolescent sexuality and public policy. AB - In recent decades, various attempts have been made to determine the level of sexual activity among adolescents. This information has been used in the planning and evaluation of sex-related programs. However, there is a flaw in using only the initial estimates of the behavior--that a sexually active person is defined as one who has had sexual intercourse. This narrow definition distorts the perception of adolescent sexual behavior. Sexual activity can more accurately be designated by focusing on the actual frequency with which teenagers have sex. In this research report, adolescents were considered sexually active if they had had sex within the last four weeks. Using this definition, adolescents were found to be substantially less sexually active than has been previously reported. This finding was then used to look at various policy decisions in the areas of sex education, family planning, and sexually transmitted disease prevention. PMID- 1927673 TI - Adolescents' reactions to the death of a peer. AB - In recent years, more attention has been given to the fact that grieving is a process, especially in the work of Elizabeth Kubler-Ross. The literature has focused on many aspects of bereavement, including how the process may be different at different ages. Much of the research on adolescents has focused on reactions to the suicide of a peer. The purpose of this study was to explore adolescent reactions to the death of a peer by means other than suicide. Semistructured interviews were conducted with ten college students about their experience of losing a friend in high school. Results indicated that even after a few years, the adolescents were still struggling through the grieving process. Implications for future research and suggestions for practitioners faced with similar crises are offered. PMID- 1927674 TI - The effects of family configuration and support system failures during childhood and adolescence on college students' self-concepts and social skills. AB - This study examined the differential effects of familial configuration and support system failures in a sample of 256 college students. Regarding familial configuration, the results indicated that individuals who had experienced parental divorce were significantly more likely to have encountered parental hostility and/or lack of care, inadequate supervision when not in school, lack of concern by teachers, and more financial hardship. In turn, lower self-concepts and/or social skills were found to be associated with these kinds of life experiences (i.e., support system failures). PMID- 1927675 TI - Do adolescents help and share? AB - Although developmental and social psychologists have studied prosocial behavior for the past twenty years, its occurrence in adolescents has received little attention. In the present paper, observational and self-report data were collected on 37 nonhandicapped and handicapped (behaviorally disordered) adolescents in public school settings. Helping, sharing, cooperating, comforting, defending, donating, and rescuing were the prosocial behaviors investigated. The adolescents with handicaps displayed significantly more prosocial behavior than did the nonhandicapped adolescents. However, the nonhandicapped adolescents perceived themselves as engaging more frequently in prosocial behavior than did their handicapped peers. The teachers of the handicapped adolescents used a prosocial teaching style more frequently than did the teachers of the nonhandicapped adolescents. Implications for future research and training are discussed. PMID- 1927676 TI - Familial correlates of sexually active pregnant and nonpregnant adolescents. AB - The relationship of familial, demographic, and individual characteristics to the probability of pregnancy was examined among 124 sexually active adolescent females. Logistic regression analyses revealed that adolescent pregnancy status was a function of a combination of demographic and familial variables. Adolescents who were pregnant at the time of the study perceived their families as having low levels of family strength, perceived communication with parents as closed, came from homes characterized by family fragmentation (i.e., only one parent or no parent living in the home), came from low-income households, were unlikely to use any method of birth control, and were more likely to be married than their nonpregnant counterparts. PMID- 1927677 TI - The relationship of adolescent peer groups to the incidence of psychosocial problems. AB - This study combined a treatment sample (n = 127) and a control sample (n = 114) of adolescents (ages 13-17) to investigate the relationship between adolescent peer groups and incidence of psychosocial problems. A content analysis resulted in four separate types of peer groups. The group with the lowest level of involvement in school activities was labeled by other adolescents in negative terms. An analysis of variance indicated that the least involved and most negatively labeled group generally had the most positive attitudes toward alcohol and drug use, the lowest levels of perceived harm due to alcohol and drug use, and the highest levels of alcohol abuse, drug use, delinquency, and depression. This group also had the lowest level of self-esteem, most external locus of control, least perceived access to occupational opportunities, and highest level of societal estrangement. The results are interpreted as providing support for both control and labeling theories. Implications for theory-based intervention are discussed. PMID- 1927678 TI - The metabolic requirements of functional activity in the human brain: a positron emission tomography study. PMID- 1927679 TI - Neural control of islet function by norepinephrine and sympathetic neuropeptides. AB - It is clear that the sympathoadrenal system has a role in the regulation of endocrine pancreatic function and that the sympathetic nerves of the pancreas can change pancreatic hormone secretion to increase the availability of metabolic fuels. It seems likely that the classical sympathetic neurotransmitter, NE, acts in concert with peptide co-transmitters, such as galanin and NPY. Each is released during the stimulation of pancreatic sympathetic nerves and each is capable of influencing either islet function or pancreatic blood flow. There is considerable indirect evidence that the sympathetic innervation of the pancreas is activated during acute stress and influences the endocrine pancreas. However, proving such a physiologic role is difficult because of redundant mechanisms that influence the secretion of the metabolically-crucial hormones, insulin and glucagon. Such definitive proof therefore awaits the development of new techniques to dissect and dissociate these mechanisms. PMID- 1927680 TI - Proglucagon-derived peptides in the neuroendocrine system. AB - Using several novel in vitro culture systems, we have examined the tissue specific regulation of the proglucagon-derived peptides, at the levels of proglucagon gene expression and pGdp synthesis and secretion. Our studies indicate that proglucagon gene expression in intenstine, hypothalamus and pancreas is under the regulatory control of protein kinase A- but not a protein kinase C-dependent pathway. PKA and PKC stimulate secretion of the intestinal pGdp's, whereas only PKA stimulates secretion of the hypothalamic peptides. Pancreatic glucagon secretion in response to PKA is subject to further modulation by prevailing glucose concentrations. This diversity in intracellular regulation of the pGdp's may account for some of the tissue-specific differences in synthesis and secretion of the pGdp's that we have observed in diabetes and during development. PMID- 1927682 TI - Hypoglycemia, gluconeogenesis and the brain. PMID- 1927681 TI - Effect of stress on glucoregulation in physiology and diabetes. AB - To examine the glucoregulatory responses to stress and their impact on diabetes, we used the following models of stress: A) Hypoglycemia; B) Epinephrine infusion; C) intracerebroventricular (ICV) injection of carbachol, an analog of acetylcholine. A) Hypoglycemia induces release of all counterregulatory hormones. During acute hypoglycemia, glucose production increases initially mainly due to glucagon release but eventually also due to a very large increment in catecholamines. In newborn dogs, neither epinephrine nor glucagon respond to a decrease in plasma glucose. This lack of a safeguard against hypoglycemia may indicate that the brain in pups is less dependent on a normal supply of glucose as a fuel, than in adult dogs. Counterregulation is enhanced when the effects of endogenous opiates are blocked by naloxone, indicating that endogenous opiates play a regulatory role during hypoglycemia. However, beta-endorphins which can be released with epinephrine during various stress situations, potentiate the peripheral effect of epinephrine. Glucoregulatory responses, even to slight changes in plasma glucose, are greatly enhanced during glucocorticoid treatment. This apparently reflects the greater sensitivity of the liver to glucagon. In diabetic dogs, similar to human diabetics, the glucagon response is abolished and the response of the catecholamines is partially decreased. On the basis of histological studies, we proposed that the deficient glucagon response in diabetes could be related to an increase in the somatostatin-glucagon ratio in the diabetic pancreas. This ratio is further augmented when normoglycemia is maintained with insulin. In response to a decrease in plasma glucose, there is a biphasic increment in glucose production in normal dogs, which is missing in diabetes. When normoglycemia is restored in diabetic dogs with phlorizin treatment, the second but not the first increment in glucose production is restored. We postulated, therefore, that the toxic effect of hyperglycemia, in addition to the lack of glucagon response, is the main reason why in diabetes, glucose production cannot respond promptly to a decrease in plasma glucose. The low rate of metabolic clearance of glucose seen in diabetes in the post absorptive state, also reflects, at least in part, the toxic effect of glucose, because with acute normalization of glucose with phlorizin, metabolic glucose clearance substantially improves. Hyperglycemia is the main reason for the decreased number of glucose transporters in diabetic muscle. B) Epinephrine infusion in normal dogs mimics some effects of stress, in that it increases glucose production, inhibits metabolic glucose clearance and increases lipolysis. These metabolic effects of epinephrine are independent of glucagon release.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1927683 TI - Measurement of local cerebral glucose utilization and its relation to local functional activity in the brain. PMID- 1927684 TI - Metabolism of glucose in the brain of IDDM subjects: brain metabolism in diabetes. PMID- 1927685 TI - Eating disorders as assessed by cranial computerized tomography (CCT, dSPECT, PET). PMID- 1927686 TI - Abnormal brain glucose metabolism in Alzheimer's disease, as measured by position emission tomography. AB - Resting glucose metabolism in the association neocortices, measured with positron emission tomography (PET), is disturbed early and throughout the course of Alzheimer's disease (AD), whereas resting metabolism in the primary sensory and motor neocortices is relatively spared. Neocortical metabolic asymmetries precede and predict appropriate deficits in neocortically-mediated cognitive functions in the initial course of disease, indicating that PET can be used for the early diagnosis and characterization of AD. Metabolic abnormalities of the neocortices in late-stage AD correlate with regional densities of neurofibrillary tangles but not of senile plaques post mortem, suggesting that tangle formation is important in disease pathogenesis. Despite demonstrating reduced resting glucose metabolism, visual association areas demonstrate equivalent (as percent baseline) blood flow responses in mildly-moderately demented AD patients and controls who are performing a face matching task. Thus, viability and integrity of this cortical circuitry is retained into the intermediate stages of the disease, and glucose delivery to the AD brain can be increased. PMID- 1927687 TI - A correlation between gene transcriptional activity and cerebral glucose metabolism in Alzheimer's disease-affected neocortex: cause or effect? AB - Our laboratory has measured mRNA pool sizes in neocortex afflicted with Alzheimer's disease (AD). We have observed a repression of gene expression in the temporal and parietal regions compared to age-matched control neocortex. These changes in messenger RNA pool size closely parallel the observed alterations in local cerebral metabolic rates for glucose (LCMR-g), as detected by positron emission tomography (PET). For example, deficits in both gene transcription and glucose metabolism appear to be the greatest in AD-affected superior temporal neocortex (Brodmann area 22) but are less apparent in the primary visual cortex (Brodmann area 17) or in the cerebellum. The unresolved question is whether changes in gene expression are the cause or effect of altered glucose metabolism. However, the non-random reductions in the pool size for certain neocortical mRNAs argue in favour of altered gene expression as the primary event. PMID- 1927688 TI - Optic neuropathy in the diabetic BB-rat. PMID- 1927689 TI - Blood-brain barrier transport of glucose, free fatty acids, and ketone bodies. PMID- 1927691 TI - The blood-brain barrier and the regulation of amino acid uptake and availability to brain. PMID- 1927690 TI - High resolution NMR studies of cerebral glucose metabolism in rats and humans. PMID- 1927692 TI - Energy and macronutrient intake regulation: independent or interrelated mechanisms? PMID- 1927693 TI - Novel peptides and islet function. PMID- 1927694 TI - Use of peptide probes to study brain regulation of glucose metabolism. AB - Neuropeptides may be used to stimulate or inhibit neurocircuitry involved in regulation of visceral organ function, including glucose metabolism. Through the use of different peptides with different specificities, it may be possible to characterize the neuroendocrine and autonomic pathways involved in the physiologic regulation of glucose homeostasis. PMID- 1927695 TI - Relationships between the hypothalamus and adipose tissue mass. AB - The brain, particularly certain nuclei of the hypothalamus and their neural connections, have a major influence on energy balance, through effects on both food intake and energy expenditure. As summarized in Table 1, there are indeed extensive interactions between the hypothalamus and adipose tissue, the predominate site of storage of chemical energy. Structural, and possibly functional, abnormalities of the neural structures facilitate the development of obesity. This review has described four components of the interactive system. Two of these components are still partly conjectural; while we have increasing experimental support, the hypothalamic-pituitary-adipose axis and the hypothalamic-efferent neural-cytoskeletal pathway are the subject of continuing intense investigation. More complete knowledge of the pathophysiology of obesity will, in turn, facilitate prevention and treatment of corpulence, as well as such frequent associations as non-insulin dependent diabetes mellitus. PMID- 1927696 TI - Biotinidase deficiency. PMID- 1927697 TI - The ventilatory pump: neonatal and developmental issues. AB - This review documents the current knowledge with regard to the structure and function of the developing ventilatory pump. We note that while the neonate's compliant rib cage and diaphragmatic configuration may predispose the newborn to pump failure, its diaphragmatic endurance properties and ability to recruit accessory muscles of respiration may protect against such impairment. We also share evidence that central neural failure can lead to an inability to defend minute ventilation during periods of heightened respiratory effort. Nevertheless, our fund of knowledge remains limited and at this juncture it is unclear which factors or interplay of factors contribute to the development of ventilatory failure in the human neonate and infant. The ventilatory pump is a vital component of the respiratory system. As such, our understanding of the pathogenesis and reversal of ventilatory pump impairment is crucial to improving our management of respiratory failure. We are only beginning to develop such an understanding within a neonatal and developmental context. Future research endeavors will enlarge our fund of knowledge regarding the thorax, the respiratory muscles, and the central neural respiratory-related neurons that control them. From such an understanding will emerge clinically relevant information that has therapeutic implications for the care of newborns and infants with respiratory disease. PMID- 1927698 TI - Diagnosis and imaging of the fetal and neonatal abdominal mass: an integrated approach. AB - Almost all of the renal causes of NAM and adrenal neuroblastoma, the most common nonrenal cause, can be categorized as cystic or solid by sonography. Evaluation with CT is usually the most appropriate next step for assessment of solid renal tumors lacking clinical features of RVT. Renal scintigraphy and diuretic renal scintigraphy offer valuable information about relative individual kidney GFR and excretory function, whether normal, partially, or completely obstructed. Many dilated urinary tracts, especially those diagnosed in utero, are found to resolve spontaneously when serial studies are performed. The informed pediatrician should play a major role in the selection of diagnostic procedures and determination of management strategy. Only he or she has the detailed clinical knowledge of the patient that can give appropriate direction to the consultants. A tentative algorithm for imaging studies in the evaluation of NAM is presented in Figure 1 and emphasizes the functionally more informative radionuclide studies 15,25,26 over the traditional radiocontrast studies. PMID- 1927699 TI - Stroke in children. AB - Childhood stroke, although similar to adult stroke, is characterized by congenital and genetic causes. The evaluation and treatment of the child with stroke requires special considerations. Currently, drug therapy is untested and as a result, therapeutic interventions are problematic. Platelet antagonists are rational prophylactically; warfarin probably has a role in preventing cardiogenic embolus in the older child. However, chronic anticoagulation in the toddler is dangerous due to frequent trauma and is therefore relatively contraindicated. Vascular malformations are surgically repaired but alternative therapies, including radiation and embolization, may be used for inoperable lesions. Aneurysms are primarily surgical lesions. Newer imaging modalities will clarify the pathophysiologic picture and improve treatment. PMID- 1927700 TI - Pediatric brain death: current perspectives. PMID- 1927701 TI - Hematopoietic growth factors. PMID- 1927702 TI - Tuberculosis in children. PMID- 1927703 TI - Urinary tract infection in infancy and childhood. PMID- 1927704 TI - Appreciating neonatal pain. PMID- 1927706 TI - Ethics education in medicine. PMID- 1927705 TI - Learned helplessness and the pediatric burn patient: dressing change behavior and serum cortisol and beta-endorphin. PMID- 1927707 TI - Advances in pediatric pharmacology and toxicology. PMID- 1927708 TI - The oculocerebrorenal syndrome of Lowe. PMID- 1927709 TI - Contemplations on genes and biological functions. PMID- 1927710 TI - Adenocarcinomas of the nose after exposure to wood dust. PMID- 1927711 TI - International variation in the incidence of cancer of the upper digestive and respiratory tract. PMID- 1927712 TI - Epidemiology of head and neck cancer in eastern Austria. PMID- 1927714 TI - Variations in histopathogenesis of squamous cell carcinoma of the upper aerodigestive tract. PMID- 1927713 TI - Cancer of the endolarynx, epilarynx and hypopharynx in south-western Europe: assessment of tumoral origin and risk factors. PMID- 1927715 TI - Multiple primary malignancies. PMID- 1927716 TI - Immunity and autoimmunity. With special reference to inner ear diseases. PMID- 1927717 TI - Experimental immunology of the inner ear. PMID- 1927719 TI - Immune-mediated inner ear disorders: an otoimmunologist's view. PMID- 1927718 TI - Vimentin as a possible cytoskeletal marker for regeneration in the human cochlea. PMID- 1927720 TI - Autoimmune inner ear disease: results of therapy. PMID- 1927721 TI - Autoimmune inner ear disease: fact or fantasy? PMID- 1927722 TI - Immunopathology and autoimmunity: the view of an immunopathologist. PMID- 1927723 TI - Aetiology of head and neck cancer: tobacco, alcohol and diet. PMID- 1927724 TI - [Psychosocial components of illness in the child]. AB - In 77 children aged 1 year the mother-child interaction in relation to the morbidity of the child was analysed. The following factors appeared to be correlated to the quality and quantity of the mother-child interaction: (i) the date of the first acute illness, (ii) the frequency of illness during the first year of life, (iii) the duration, frequency and seriousness of the illnesses after admission to day care at the age of one year. Conclusions are drawn for the practice of infant care. PMID- 1927725 TI - [Are boys less intelligent? A plea for different school admission ages for boys and girls]. AB - This critical survey presents arguments in favour of different dates for admitting boys and girls to school. The authors refer to their own research to demonstrate that differences in the speed of maturing have negative educational consequences for young school children, especially boys, which could be avoided in a future school system with more flexible dates for school entrance. PMID- 1927726 TI - [Possibilities for the detection and monitoring of children and adolescents with hypertension]. AB - Blood pressure measurements have been taken for ten years or more on the basis of a standard programme as part of the paediatric mass screening, starting with the second medical examination for school entrance. They have now become an integral component of this checkup routine. The following recommendations are made for a revised prophylactic examination programme: enlargement of case history questionnaire on arterial hypertension, maintenance of present valid norms and recommendations for medical attention in cases of high blood pressure risk, and blood pressure measurements for school entrants in grades 6 and 9. PMID- 1927727 TI - [Two-year health-education for students: effects on serum lipids]. AB - This report concerns the development of total and HDL-cholesterol serum values after a two year health education programme for school children aged 13 or 14 at the beginning. Of altogether 521 pupils who were examined again after two years, 281 had completed an intervention programme with an emphasis on healthy diet, encouragement of non-smoking and physical activity. The others had not taken part in the programme and formed the control group. Concerning cardiovascular risk, the average levels of total and HDL-cholesterol in the serum were generally more favourable after the two year intervention period than in the group uninfluenced by the health education programme. PMID- 1927729 TI - [8th International Congress on child abuse and neglect, 2-6 September 1990 in Hamburg]. PMID- 1927728 TI - [Atherosclerosis and hypercholesterolemia in pediatric and adolescent medicine]. PMID- 1927730 TI - Old people in hot weather. PMID- 1927731 TI - Hypotension as a risk factor for the development of pressure sores in elderly subjects. AB - The systolic (sBP), diastolic (dBP) and mean (mBP) blood pressure were measured in hospitalized geriatric patients with (n = 30) and without (n = 100) pressure sores. A more intensive investigation was carried out in 18 elderly hospitalized geriatric patients without pressure sores, who were compared with 10 healthy young and 10 healthy elderly subjects. In these groups, the blood pressure was compared to the skin blood cell flux (SBF) as evaluated by the laser Doppler technique, at rest and during the post-occlusive reactive hyperaemia (PRH) response in the sacral area which is a high risk area for pressure sores. The patients with pressure sores had a significantly lower sBP (130 +/- 17 mmHg) compared to patients without pressure sores (140 +/- 20 mmHg). A significant correlation between a low resting SBF and a low mBP was found in all groups. An impaired PRH response corresponded to a low sBP in the two elderly groups. No correlation to dBP was seen at all. It is concluded that low mBP and sBP in elderly hospitalized patients were significantly correlated to a low resting SBF and a impaired reactivity of the skin microcirculation, respectively, and a low sBP was associated with pressure sores. Measurements of the systemic BP are of importance when classifying patients at risk of pressure sores. PMID- 1927732 TI - Urinary incontinence among the elderly people of Singapore. AB - In a sample of 919 respondents aged 65 years and older, resident in a public housing estate in Singapore, the prevalence of regular urinary incontinence was 4.6%. Thirty-five of the 42 incontinent subjects consented to a detailed interview. The majority of these 35 cases leaked urine daily, leaked amounts over one tablespoon, or were suffering some psychological [corrected] or social effect of the incontinence. Urge incontinence was the commonest type in women and outlet obstruction in men. Almost all incontinent subjects were agreeable to having medical attention for the condition although over a third had not previously consulted medical personnel about the problem. There may be scope for the provision of primary health care continence services. PMID- 1927733 TI - Comparison of interface pressures measured at the sacrum while resting upon two types of foam mattresses and between platilon and plastic mattress covers. AB - We investigated the pressure-redistributing characteristics of a 5-inch foam mattress compared with the Clinifloat slotted mattress fitted with a Platilon cover or with a tight-fitting plastic cover. We confirmed earlier work showing that a loose-fitting cover is necessary for the effectiveness of the slotted mattress. PMID- 1927734 TI - The role of hospitals in caring for people in the last year of their lives. AB - This study explored the role of hospitals in caring for people in the last year of their lives by examining hospital use and the characteristics of people admitted to hospital and changes between 1969 and 1987. Results were based on an 80% random sample of 800 adult deaths in ten areas of England in 1987. People dying when they were 85 or more were the least likely to be admitted to hospital in the last year of their lives. Results raise questions about the traditional emphasis of hospital care, the training of medical students, the adequacy of care for the very elderly in the last year of their lives and the balance of care between the hospital and the community. PMID- 1927735 TI - A study of well-being of elderly people in three communities in Zimbabwe. AB - The purpose of this research was to assess the well-being of elderly people in three different community types in Zimbabwe. Well-being was defined as general health, health resource access, nutrition, habits, and physical function. Major health problems, hygiene, nutrition and access to health care did vary between communities, but there was a low level of physical dependency throughout. The findings suggest that once a critical decline in fitness occurs, elderly people may rapidly die as a result of diminished medical and physical support. These findings are relevant to future plans for elderly care services in Zimbabwe. PMID- 1927736 TI - Primary health care consumerism amongst elderly Australians. AB - Despite acceptance of many of the principles justifying government intervention in health care provision and financing, much recent market-based policy in Australia, the USA and the UK has been based on the assumption that patients have the potential to behave as 'good consumers'. Good consumers are patients with the ability and desire to seek out health care of good quality and reasonable cost. In this paper, an exploratory survey of general practice attenders in Western and Northern Sydney is reported. The aim of the survey was to assess the extent to which patients critically select and evaluate their general practitioner, as a good consumer may be expected to do. The results demonstrate a lack of consumer oriented behaviour both in general and amongst older respondents in particular. If such results hold true, market-based health care policies relying on consumers to judge quality of care are likely to be detrimental to the health of older people. PMID- 1927737 TI - Impaired splenic function in elderly people. AB - Splenic function was assessed in subjects aged 70 years or over by counting pits in erythrocytes viewed under differential interference contrast microscopy. An increased percentage of pitted cells has previously been described after splenectomy and in medical hyposplenism. The mean percentage of erythrocytes with one or more pits was significantly higher in 40 elderly patients (3.4%) than in 40 younger patients (1.6%), confirming the results of a previous study on a Brazilian population. There was greater variability of splenic function in the elderly subjects with a subgroup with a greatly increased percentage of pitted erythrocytes. Impaired splenic function may predispose elderly patients to pneumococcal infection. This relationship deserves further study. PMID- 1927738 TI - Incidence and prevalence of thyroid disease in elderly women: results from the longitudinal population study of elderly people in Gothenburg, Sweden. AB - The incidence and prevalence of thyroid dysfunction were estimated in a longitudinal study of a representative sample of elderly women at ages 70, 75, 79 and 81. Thyroid-stimulating-hormone concentrations were measured in frozen samples obtained at the ages of 70 and 75 that had been stored for ten and five years, respectively. At the ages of 79 and 81 the serum concentrations of thyroid stimulating hormone were determined in connection with the sampling. For comparison, thyroid-stimulating-hormone concentrations were also measured in another representative population sample of women at ages 70 (n = 297) and 76 (n = 342), in whom measurements were carried out in direct connection to the clinical study. History of previous thyroid disease, e.g. thyroid surgery and thyroid hormone treatment, was obtained through a questionnaire. Information about previous treatment with radio-iodine was obtained from records. At the age of 70, 1.9% had had thyroid surgery but none had been treated with radio-iodine. L-Thyroxine had been prescribed for 3.5%, and another 3.9% had high thyroid stimulating-hormone concentrations (greater than 10.0 mU/l) indicating thyroid hypofunction. Between 70 and 79 years of age, eight of the 514 women had developed high concentrations of thyroid-stimulating hormone and another two women had received treatment with L-thyroxine. Three women had received radio iodine therapy. In addition, one woman at the age of 81 was discovered to have hyperthyroidism. The retrospective analysis showed that markedly elevated TSH concentrations had been present in several women for at least nine years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927740 TI - [Macular hole]. PMID- 1927739 TI - Mitral balloon valvuloplasty for patients aged over 70 years: an alternative to surgical treatment. AB - We report the results and one-year follow-up of 20 elderly patients (age range 70 82 years) with severe rheumatic mitral stenosis treated by mitral balloon valvuloplasty (MBV). All 20 were breathless at rest despite treatment with diuretics and digoxin. At cardiac catheterization, successful dilatation was achieved in 17 patients: mean transvalvular mitral gradient fell by 45%, mean cardiac output rose by 24% and mean valve area increased by 76%. There was no procedure-related mortality. At one month, 15 patients had experienced an improvement in symptoms of at least one New York Heart Association class and, at one year, ten had maintained this improvement. Three patients proceeded to mitral valve replacement because of a suboptimal symptomatic result. Mitral balloon valvuloplasty can be successfully performed with significant symptomatic benefit in frail elderly patients unfit for surgery and may also be offered to other selected elderly patients as an alternative to surgical treatment. PMID- 1927741 TI - [The mechanism of corneal ring formation caused by bacterial endotoxin]. AB - Corneal ring can be produced experimentally by injection of endotoxin into the rabbit cornea. To clarify this phenomenon, the effects of inhibitors of arachidonic acid metabolite were studied on the formation of the corneal ring. Phospholipase A2 inhibitor (dexamethasone) and lipoxygenase inhibitor (TEI-3308) blocked the accumulation of polymorphonuclear leukocytes (PMNs) in the endotoxin injected cornea, while cyclooxygenase inhibitor (indomethacin) enhanced PMN accumulation. This result suggests that products of the lipoxygenase reaction of arachidonic acid are related to the formation of the corneal ring induced by endotoxin. The existence of endotoxin in active form for a long period was also demonstrated immunohistochemically. PMID- 1927742 TI - [The effect of interleukin-1 on ocular inflammation in rabbit ocular tissue]. AB - IL-1 (Interleukin-1) has attracted attention not only as a mediator of the immunological response but as a substance involved in acute and chronic inflammatory responses. The author induced endophthalmitis by intravitreous injection of IL-1 into rabbit eyes. The inflammation model was characterized by the indicators of aqueous humor protein and PGE2 levels, and IL-1 and PAF were investigated as possible mediators of inflammation in IL-1 induced endophthalmitis. A prostaglandin (PG) synthetase inhibitor suppressed both the protein level and PGE2 level, while a PAF antagonist acted to inhibit the increase in the protein level in aqueous humor but did not inhibit the rise in PGE2. Combined administration of the PAF antagonist and the PG synthetase inhibitor further reduced both the protein and PGE2 levels. These findings suggest that PAF may be a mediator of endophthalmitis due to IL-1, and that IL-1 induced endophthalmitis is also modified by other factors in addition to PAF. PMID- 1927743 TI - [Interaction of antiglaucomatous drugs and melanin granule]. AB - The author investigated the effects of several antiglaucomatous drugs and prostaglandins (E2 and F2 alpha) on intraocular pressure responses in pigmented and albino rabbits, and spectrophotometrically assessed the binding of these drugs to synthetic melanin. Topical application of 0.5% timolol, 1% epinephrine and 3% pilocarpine had greater ocular hypotensive effects in albino rabbits than in pigmented rabbits. However no such differences were seen with application of prostaglandins. Melanin binding of drugs was higher in the order of befunolol, carteolol, timolol, epinephrine and pilocarpine. At higher concentrations of the drugs, the degree of binding increased. Prostaglandins had no binding ability. Thus drugs with lower hypotensive effects in pigmented rabbits than in albino rabbits had high melanin binding ability, whereas drugs with similar effects in pigmented and albino rabbits had no melanin binding ability. It is speculated that some antiglaucomatous drugs bind to melanin, resulting in decreased pharmacological action. PMID- 1927744 TI - [The development of the Schlemm's canal in human eyes]. AB - The fetal development of Schlemm's canal of the human eye was investigated by light and electron microscopy. Schlemm's canal was not yet a circumferential structure at the 20th fetal week, and at the 26th fetal week the canal appeared to form by a process of confluence of the channels. As development proceeded, the canal positioned relatively anterior to the apex of the angle, as a result of posterior shift of the angle recess. The remarkable increase in the width of the canal during the fetal period was mainly achieved by the elongation of the endothelial cells, whereas the number of endothelial cells in meridional sections did not alter. From the 26th fetal week onward, the frequency of giant endothelial vacuoles and pores increased together with the discontinuity of the basal lamina, which corresponds with the increase of aqueous flow. PMID- 1927745 TI - [Internal sclerostomy with a high-powered argon laser]. AB - A full-thickness sclerostomy from the anterior chamber to the subconjunctival space was created in 9 eyes of 7 rhesus monkeys using an argon endolaser. After the injection of sodium hyaluronate into the subconjunctival space and the anterior chamber, a 300 microns fiberoptic fiber coupled with an argon laser (HGM, model 20) was inserted to the anterior chamber and positioned at the trabecular meshwork. A patent sclerostomy was created in all 9 eyes by 1 to 3 laser pulses with an energy of 4W with a duration of 0.5 second. Preoperative intraocular pressure in treated eyes and untreated eyes, measured with a pneumatic tonometer, was the same. After one month, the intraocular pressure of the treated eyes was 4.6 +/- 0.4mmHg lower than that of the untreated eyes. Histologic study revealed that the sclerostomies with a diameter of 200-300 microns from the anterior chamber opening to the subconjunctival space were patent at one month after the treatment. Internal sclerostomy with a high powered argon endolaser may hold potential as a new filtering procedure which can easily be performed with a minimum of conjunctival damage. PMID- 1927746 TI - [Analysis of cone-mediated c-waves of the chicken ERG using the spectral sensitivity under monochromatic light adaptation]. AB - ERG c-waves were recorded from eyes of anesthetized chickens by stimulating with monochromatic bright light ranging from 460 to 620nm, under yellow or red light adaptation, using various energy levels i.e. 1, 3, 4 and 5W/m2 at the corneal surface in the former, and 3, 4 and 5W/m2 in the latter. After recording a series of c-waves, the spectral sensitivity curve for each adaptation condition was obtained. Amplitude-intensity curves showed that amplitudes increased with increment of stimulus luminance. The energy required to release a response of a given criterion magnitude was determined at each of the wavelengths investigated. The peak wavelength of the spectral sensitivity curve of the c-wave under both yellow and red light adaptation was 520 or 540nm both of which were shorter than the peak wavelength (560nm) under white light adaptation. These results showed that under the yellow and red light adaptation the sensitivity of the c-wave response to monochromatic light in the longer wavelength range was suppressed, suggesting the possibility of isolating cone-mediated c-wave response. A peak (520 or 540nm) and a shoulder (580nm) in the spectral sensitivity curves were presumed to be derived from two types of cone systems. PMID- 1927747 TI - [Morphological changes in the retina following one-shot injection of netilmicin sulfate into the vitreous]. AB - Morphological changes of the retina following one-shot injections into the vitreous of netilmicin sulfate were investigated. The concentrations of netilmicin in the vitreous after intravitreal injection showed the curve of y = a/xb, where y is the concentrations in the vitreous body, x in the number of days since injection and a, b are constant. Concentration decreased rapidly after the injection, and almost totally disappeared after one week. Morphologically, the retina showed normal structure following injections of 100 micrograms/0.1ml and 200 micrograms/0.1ml. Following injections of over 500 micrograms/0.1ml, the outer segment of the photoreceptor disappeared and many phagosomes appeared in the retinal pigment epithelium cell. Following one shot injections of over 500 micrograms/0.1ml damage to the photoreceptor and retinal pigment epithelium was demonstrated. The above data suggested that one-shot injection of netilmicin in concentrations of up to 200 micrograms/0.1ml could be mode without retinal damage. PMID- 1927748 TI - [The state of the vitreous in idiopathic macular holes]. AB - We examined the vitreous of 37 eyes of 31 patients with macular holes of various stages. There was no posterior vitreous detachment (PVD) in 18 of 18 impending and 19 of 20 newly formed macular holes. In newly formed macular holes, the operculum was located either at the level of or immediately anterior to the retinal surface. The gel component of the vitreous was always separated from the posterior fundus by intervening liquefied lacuna, simulating PVD. However, the cortical vitreous was located posterior to the liquefied lacuna and remained attached to the retina. PVD failed to develop in all of 15 eyes during the follow up period of 3 months after formation of a macular hole. The incidence of PVD increased in the eyes with macular holes lasting for 1 year or longer. In our present series, PVD in its classical sense did not contribute to the pathogenesis of macular holes as it developed after formation of the latter. Instead, a subtle anterior displacement of vitreous cortex strictly confined to the area of the fovea seemed to trigger the development of idiopathic macular holes. PMID- 1927749 TI - [Prognosis of fellow eyes in idiopathic macular hole cases]. AB - We studied contralateral eyes in 62 cases of unilateral idiopathic macular hole to determine their prognoses and risk factors for this disorder. At the initial examination, 11 of 62 eyes (18%) showed a macular cystic lesion, and 18 (29%) showed a yellow spot in the fovea. During a mean follow-up of 39 months, macular holes eventually developed in 6 of the 11 eyes (55%) with macular cystic lesion and in 4 of 18 eyes (22%) with a yellow spot. Macular holes, however, did not develop in eyes with vitreous separation in the fovea or with a normal macula. Moreover, the macular lesion apparently improved in 14 of 29 eyes (48%) with early stage macular holes. These fourteen eyes showed vitreous separation in the fovea at the initial examination or at the follow-up examination. Therefore, eyes with macular cystic lesions and without posterior vitreous separation are at high risk of a macular hole developing, although these eyes have a chance for improvement by spontaneous vitreous separation. PMID- 1927750 TI - [Study of follow-up period and provocative tests for diagnosis of primary open angle glaucoma]. AB - How long should we follow up the patients with glaucomatous visual field defects to confirm the diagnosis of primary open-angle glaucoma (POAG)? What is the most important examination for the diagnosis of POAG? In order to answer these questions, 108 eyes of 60 cases were followed up for more than 4 years. All of these subjects presented both open angle and glaucomatous field defects. In the patients who did not present the increment of the intraocular pressure (IOP) within one month from the first visit, the relationship between the increment of IOP after one month and provocative tests, sex, age and refractions were evaluated. Of these, 47 eyes showed an increment of IOP within one month from the first visit. The other 61 eyes, suspected of low tension glaucoma (LTG), were followed up for the further course of IOP. Of these, 25 eyes showed an increment of IOP after one month to 6 years from the first visit, and the other 36 eyes did not for more than 4 years to 21 years. Follow-up for at least one year is necessary to confirm the diagnosis of POAG. In order to predict the increment of IOP in the subjects with normal IOP and glaucomatous field defects, the ratio Po/C after drinking water is the most sensitive examination. PMID- 1927751 TI - [Insertion anomalies of the horizontal muscles and dysfunctions of the oblique muscles in the A-V patterns]. AB - Insertion anomalies of the horizontal rectus muscles and dysfunctions of the oblique muscles were studied in 141 cases with A-V patterns of 824 patients with horizontal strabisums. The frequency of insertion anomaly among all cases of A-V pattern studied was 49.6%, there were more V pattern insertion anomalies than in those of A pattern, but the ratio of insertion anomalies in each type of A-V pattern was more in the A pattern than in the V pattern. In the oblique muscles, overaction of the inferior oblique muscle in the V pattern and of the superior oblique muscle in the A pattern were frequently encountered and insufficient action of the oblique muscles occurred more frequently in cases A-V esotropia than in cases of exotropia. In cases of combination of insertion anomaly of the horizontal rectus muscles with dysfunction of the oblique muscles, insertion anomaly was involved in 91.3% of cases of overaction of the superior oblique muscles, but only in 37.4% of cases of overaction of the inferior oblique muscles. The combination of insertion anomalies with dysfunction of the oblique muscles suggests a possible existence of simulated dysfunction of the oblique muscles in some cases of dysfunction of the oblique muscles diagnosed preoperatively. At the choice of a procedure in surgical correction, a confirmation of insertions of the horizontal muscles during operations is needed, and for this purpose the perilimbal incision is more appropriate than the fornix incision. PMID- 1927752 TI - [Choroidal detachment associated with spontaneous carotid cavernous fistula]. AB - A rare case is presented in which an 87-year-old woman with choroidal detachment was subsequently found to have an atypical carotid cavernous fistula (CCF). In this case, the intraocular pressure of the affected eye was higher than that of the contralateral eye. However, tonography showed no increased ocular pulse (amplitude of Schioetz reading) of the affected eye, which is characteristic of CCF. Choroidal detachment accompanied with CCF is thought to be a result of severe choroidal hemostasis and transudation caused by increased episcleral venous pressure. Furthermore, the enlarged perichoroidal space due to choroidal detachment reduced the ocular pulse of the affected eye. This combination may not be as rare as it has been previously reported. Attention to these symptoms can provide clues to the elucidation of the pathogenesis of choroidal detachment. PMID- 1927753 TI - [Neurophysiopathology of spinal lesions, evaluation of the 80s. Post-injury assessment and treatment of the neurogenic bladder in the acute period]. AB - This introductory presentation deals with the recent pathophysiological aspects of the post-traumatic spinal cord lesion and the population concerned. The neurophysiology of the bladder and its sphincters is summarized so as to try and explain some disturbances occurring during the acute phase following a spinal cord injury; their clinical and urological aspects and the methods of bladder drainage. PMID- 1927754 TI - [Scrotal contusions]. AB - The author reports 8 cases of serious scrotal contusion, requiring urgent intervention with simple drainage castration or suture of the tunica albuginea. It is desirable to operate with in 6 hours in order to avoid ischaemic disorders of the testicle. PMID- 1927755 TI - [Inverted papilloma of the urothelium]. AB - The authors report 4 cases inverted papilloma of the urothelium. They describe the clinical, evolutive and pathological aspects of this rare tumor. PMID- 1927756 TI - [Hypernephroma with contralateral renal artery stenosis. Therapeutic choices]. AB - We report a case of renal adenocarcinoma with contralateral stenosis of the renal artery. We describe the causes of hypertension in renal cancer and investigative techniques leading to the discover of a vascular implication in hypertension. We debate of the different surgical techniques for renal revascularisation with special regard to splenorenal anastomose. This is the method of revascularisation used in this case. PMID- 1927757 TI - Malignant schwannoma of the adrenals. A rare case. AB - This a rare case of malignant adrenal schwannoma in a woman aged 38 years old without family history of neurofibromatosis. A diagnosis is impossible before surgery. PMID- 1927758 TI - Bladder cancer in a young girl with systemic lupus erythematosus treated with cyclophosphamide. PMID- 1927760 TI - [The contribution of electrophysiological tests in the assessment of paraplegia]. AB - Electrophysiological techniques have significantly improved in the last decade. The authors present a short list of the available current techniques. PMID- 1927759 TI - [Current urological management of traumatic paraplegia]. AB - The management of patients with neurological dysfunctions of the bladder and the sphincter is considerably modified in recent years. The concept of "neurogenic bladder" has evolved due to new fundamental neurophysiological research following the advances of urodynamic investigations and medical imaging techniques as well as progress in drug therapy, surgical treatment and re-education. The current management of a traumatic paraplegia should therefore be prospective and must try to determine prognostic factors. PMID- 1927761 TI - [Electric and magnetic brain mapping following stimulation of the dorsal nerve of the penis or clitoris]. PMID- 1927762 TI - [The York-Mason repair method of a prostato-rectal fistula]. AB - Rectoprostatic fistulas following surgery pose difficult problems for surgical reconstruction. A variety of surgical techniques has been proposed including a perineal trans-sphincteric approach and a York-Mason procedure. We repaired three patients by this approach; we found the intervention simple, safe and effective; preliminary colostomy is not necessary. PMID- 1927763 TI - [Ureterocele and duplication. Reparative surgery using tubulization of the ureterocele]. AB - The authors report three cases of a ureterocele and duplication of the ureter and the surgical technique using a flap of the surface of the ureterocele itself. This facilitates surgical repair of this anomaly and prevents dissection of the terminal section of the two ureters. PMID- 1927764 TI - [Rehabilitation of male incontinence following prostate surgery. Results in 35 patients]. AB - Incontinence after surgical procedures on the prostate occurs in up to 5-10% of patients. We describe a conservative treatment based on manual therapy and bladder and sphincter training. Good results were obtained in 66% of patients. Method and results are discussed. PMID- 1927765 TI - [Immunological assessment after radical nephrectomy for renal cell carcinomas pre treated with interferon-gamma]. AB - Twenty two patients with renal cell carcinoma subjected to radical nephrectomy were divided into 2 groups, the first group consisted of 10 patients who received pre-operative interferon-gamma (IFN-gamma administered group), and the second one consisted of 10 patients who received nephrectomy alone (non-administered group). An immunological assessment was made as to whether the pre-operative administration of IFN-gamma affects the immunocompetent cells before or after nephrectomy with reference to stage or grade of cancer, the duration of anaesthesia and in the absence or presence of a blood transfusion. Immunocompetent cells that we had checked were peripheral blood lymphocytes (PBL), CD3, CD4, CD8, CD16 and CD20. These cells were examined on the day before the administration of IFN-gamma (in the case of the administered group), just before nephrectomy and on the 7th day after nephrectomy. With regard to the effects of the administration of IFN-gamma pre-operatively, there were more patients who showed an increase of CD16 in the administered group, compared with the patients who showed a decrease of CD16, and its difference was significant. On the other hand, we observed that the patients who showed an increase of CD16 were low stage and low grade predominantly, but the difference was not significant. Regarding the immunological changes after nephrectomy, there appeared to be an increase in the ratio of CD4/CD8 in the administered group, and these patients were low stage and low grade significantly. As to CD16, the tendency was similar to that observed for the ratio of CD4/CD8 in the administered group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927766 TI - [Estimation of nuclear volume of nontumorous bladder mucosa in patients with bladder tumor--measurement by vertical section]. AB - The mean nuclear volume (MNV) of non-tumorous bladder mucosa in 27 patients with a bladder tumor was estimated by using a new stereological method, "vertical section". Eighty four specimens were obtained by punch biopsy from preselected sites of urinary bladder. Thirteen specimens (10 patients) out of 84 were histologically diagnosed as carcinoma in situ (CIS). Bladder mucosa of 24 patients with various benign diseases were also measured as normal controls. The MNV of the normal control group was 127.1 +/- 19.6 microns 3 (mean +/- standard error) and that of the specimens diagnosed with CIS was 279.6 +/- 69.0 microns 3. There was no overlap between the two groups. Out of 71 specimens diagnosed as having no malignancy, 30 (42.3%) exhibited significantly increased MNV. Estimation of the MNV of non-tumorous bladder mucosa may be useful for standardization of CIS. Further studies are needed to investigate the role of the increased MNV in histologically normal mucosa in the course of a bladder tumor. PMID- 1927767 TI - [Combination chemotherapy of methotrexate, etoposide, adriamycin and cisplatin (M EAP) for advanced urothelial cancer]. AB - Combination chemotherapy with methotrexate, etoposide, adriamycin and cisplatin (M-EAP regimen) was administered to 4 patients with advanced epithelial cancer of the urinary tract (Methotrexate 30 mg/M2 day 1, 15 and 22; Etoposide 100 mg/M2 day 1, 2, 15 and 22; Adriamycin 30 mg/M2 day 2; Cisplatin 70 mg/M2 day 2, every 4 weeks). In an attempt to improve the anti-cancer effect of the M-VAC regimen, etoposide was substituted for vinblastine. This series comprised 3 males and 1 female ranging in age from 54 to 68 years (mean age: 63), with a performance status of 1 to 2. The site of the primary lesion was bladder in 3, and left ureter in 1. The clinical response was assessed in 3 of the 4 patients: one achieved complete response and two had partial response. Two of the four died of disease 5 months after chemotherapy. Two of them have been alive for 10 and 8 months with no evidence of disease after chemotherapy. Toxicity included moderate or severe myelosuppression in two patients, and mild to moderate anorexia, vomiting, alopecia, and hiccups in all patients. These preliminary results suggest that the M-EAP regimen is effective against advanced epithelial carcinoma of the urinary tract. However, myelosuppression was a dose-limiting factor. PMID- 1927768 TI - [Evaluation of urinary incontinence among the nursing home elderly]. AB - We assessed the prevalence of urinary incontinence and contributory factors such as senile dementia, impaired mobility, medication, associated disorders and urinary tract infection in 98 elderly residents of a nursing home. The residents' mean age was 79 years, and 78% were women. Urinary incontinence was found in 47 (48%), of whom 21 had severe urinary incontinence for which they needed to wear diapers. Senile dementia and impaired mobility were observed in 53 (54%) and 45 (46%), respectively. We also found that those with both dementia and impaired mobility had significantly (p less than 0.01) precipitated urinary incontinence. However, no significant effects on urinary incontinence were observed for associated disorders, medication or urinary tract infection. A cystometrogram performed in 73 of the 98 residents revealed detrusor overactivity in 47%. In addition, there were significant correlations between the incidence of detrusor overactivity, and the prevalence of dementia or urinary incontinence. These results suggest that senile dementia and immobility are independent risk factors for urinary incontinence in the elderly, and that detrusor overactivity, which was found to be associated with senile dementia, is a possible cause of urinary incontinence. PMID- 1927769 TI - [Study of incidental carcinoma of the prostate. Part 1. Pathological analysis related to the clinical features]. AB - To clarify the clinico-pathological characteristics of incidental carcinoma of the prostate, we investigated a total of 590 prostatic tissues which had been operated under the diagnosis of benign prostatic hyperplasia (BPH), including 12 whole prostatic specimens which were obtained by total cystectomy due to bladder cancer. Histological examination and estimation of the tumor volume were carried out by either a 3-mm step-section in 185 prostates obtained by open surgery, or by mounting whole specimens in 405 TUR cases. Incidental cancers were detected in 69 of the 590 patients (12%) with nearly equal numbers of stage A1 and stage A2 diseases. The age and the size of the prostate were significantly greater in the patients with cancer, compared to those without cancer. However, these parameters were not in agreement with each other. Histological analysis revealed that 46 of the 69 (67%) incidental cancers were well differentiated and nearly corresponded to Gleason's sum score of 2-4. In the analysis of the differentiation of the tumor cells and the tumor extension, nearly 80% of the 23 well differentiated cancers were manifest in a single lesion and were smaller than 0.3 cm3, whereas 90% of the 11 moderately or poorly differentiated cancers were diffusely invasive. Six of the 11 cases (55%) were larger than 0.3 cm3. The prognosis of the 16 incidental cancer patients who had survived more than 5 years after the surgery were compared with the controls. The controls were selected among the cases without incidental cancer, and matched for age and the time of operation in a 1 to 2 fashion without knowledge of their prognoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927770 TI - [Clinical study of prostate cancer--statistical analysis in the last 10 years]. AB - Fifty one cases of prostate cancer were treated at Yamaguchi University Hospital during 10 years since 1975. Age distribution was between 43 and 90 years old with an average of 70.9 years. Chief complaints were difficulty on micturition (33%), complete urinary retention (19.6%), macroscopic hematuria (15.7%), and frequency (13.7%). Clinical stage was classified as 1 case (2%) with stage A, 7 cases (13.7%) with stage B, 20 cases (39.2%) with stage C and 23 cases (45.1%) with stage D cancer. Histological grade was classified as 9 cases (17.6%) with well differentiated type of adenocarcinoma, 15 cases (29.4%) with moderately differentiated type and 27 cases (52.9%) with poorly differentiated type. The 5 year actual survival rate was 75% for stage A&B, 50% for stage C and 60% for stage D. The 10-year actual survival rate was 20% for stage A&B, 17% for stage C and 20.5% for stage D. There were no statistically significant differences between stage, grade and survival rate. According to specific cause 18 cases (58%) were cancer deaths including 8 cases (15.7%) of refractory disease, and 4 cases (12.9%) of cardiovascular complication. Five of the eight refractory cases could survive over one year by multimodal treatment. Local irradiation to prostate was most effective to control symptoms against locally refractory prostate cancer. PMID- 1927772 TI - [The suction effusion fluid is useful as a sample for blood biochemistry]. AB - We examined whether the suction effusion fluid could be used as a new sample for blood biochemistry. The fluid was obtained from the skin surface of female mongrel dogs by transcutaneous suction after removal of the horny substance. The appropriate intraluminal pressure for suction was 300 mmHg at which the effusion fluid flow rate was 0.6 microliter/min/cm2. The blood biochemistry examination revealed that the creatinine (Cr) and urea (BUN) concentrations in the suction effusion fluid were similar to those in plasma and that the protein and lipid concentrations were much smaller than those in plasma. The six-hour study showed that the effusion fluid could be obtained for hours at the same skin area and that the Cr and BUN concentrations were consistently close to those in plasma. In uremia models, the Cr and BUN concentration in the suction effusion fluid was similar to and had an extremely high correlation (r = 0.985 and 0.982 respectively) to that in plasma through out the range for clinical practice. The skin biopsy revealed that the regeneration of the horny substance had started at one week after the suction and complete recovery was seen at four weeks. The invasiveness of the suction seemed to be small. The suction effusion fluid is a reliable material for measurement of Cr and BUN in plasma and, as it contains much less proteins and lipids, will be a good sample for biosensors. PMID- 1927771 TI - [Studies on 5-FU concentration in serum and prostate cancer tissue after oral administration of UFT]. AB - The serum, urine and tissue concentrations of 1-(2-tetrahydrofuryl)-5 fluorouracil (FT), 5-fluorouracil (5-FU) and uracil were estimated in 11 patients with prostate cancer (4 cases treated by total prostatectomy and 7 cases by transurethral resection (TUR-P) after oral administration of UFT. The concentration of FT, 5-FU and uracil in the tumor tissue (micrograms/g) were 5.920 +/- 5.902, 0.018 +/- 0.012 (T/S; 2.20) and 7.785 +/- 4.151 in 4 patients treated by total prostatectomy and 1.943 +/- 1.355, 0.024 +/- 0.010 (T/S; 1.46) and 4.616 +/- 2.848 in 7 patients treated by transurethral resection of prostate. The concentrations of FT, 5-FU and uracil in the tumor tissue did not increase as compared with those in normal tissue in 4 cases treated by total prostatectomy. PMID- 1927773 TI - [Retroperitoneal cavernous hemangioma: a case report]. AB - A 55-year-old man was shot at the age of 50. At that time CT revealed a mass near the spleen. Thereafter, CT did not reveal any growth of the mass, but to examine the mass in detail he was hospitalized to our department. The mass was diagnosed as left adrenal cavernous hemangioma, since, on aortography, it was typical cavernous hemangioma and fed mainly from the left inferior phrenic artery. The mass was resected with the spleen, thoracic wall, and part of diaphragma. At the operation the left adrenal gland was identified to be intact. Histopathological diagnosis was retroperitoneal cavernous hemangioma. This is the 19th case of retroperitoneal cavernous hemangioma in the Japanese literature. PMID- 1927774 TI - [Bilateral adrenal gland metastasis of renal adenocarcinoma--a case report]. AB - A 72-year-old male patient, who suffered from a renal adenocarcinoma with bilateral adrenal gland metastasis, is reported herein. The patient consulted the urology clinic with complaints of fever and dysuria. On drip infusion pyelography, a mass lesion was discovered in the upper pole of the left kidney. Computerized tomography (CT) revealed the presence of bilateral adrenal masses. On the basis of aortography and CT studies, the patient was diagnosed as having renal cancer with metastasis in bilateral adrenal glands. No other metastasis could be found. Radical left nephrectomy and bilateral adrenectomy were performed. Thereafter, interferon alpha of 3 million units every day was administered intramuscularly for the first 2 months and then, the same dose was given once a week to the present. Supplementary corticosteroids were also administered. His course was uneventful for 18 months after the operation, with no evidence of recurrence. PMID- 1927776 TI - [Transitional cell carcinoma of pelvis in a giant hydronephrotic kidney]. AB - A 73-year-old man complained of macroscopic hematuria. Preoperative diagnosis was left giant hydronephrosis due to UPJ stenosis. Resected kidney unsuspectedly contained multiple papillary tumors. Ureterectomy and partial cystectomy was additionally performed. Histological examination showed transitional cell carcinoma. Urinary stasis in the dilated pelvis may have been one of the causes of carcinomatous changes in the epithelium in our case. PMID- 1927775 TI - [Ipsilateral synchronous renal pelvic transitional cell carcinoma and renal cell carcinoma: a case report and review of the literature]. AB - A case of ipsilateral transitional cell carcinoma of left renal pelvis and left renal cell carcinoma is presented. A 75-year-old male consulted our hospital with the complaint of painless gross-hematuria which had persisted for four years. Excretory urography revealed left non-visualized kidney. Retrograde pyelography demonstrated the filling defect, which had an irregular border, in the left renal pelvis. The selective left renal arteriography revealed the hypervascular region in the left renal cortex. Intraarterial chemotherapy with CDDP, MTX and ADR was performed preoperatively. Then, total left nephroureterectomy and segmental resection of the bladder was done. The surgical specimen was pathologically diagnosed as transitional cell carcinoma of the renal pelvis and renal cell carcinoma of the left kidney. This case is the 23rd reported case of ipsilateral synchronous renal malignancy in Japan. PMID- 1927777 TI - [A case of infiltrative transitional cell carcinoma of the kidney with hypercalcemia]. AB - A 73-year-old man was admitted to our hospital with chief complaint of macrohematuria. Computerized tomography revealed enlargement of right kidney, tumor thrombi and lymph nodal involvement. Distant metastases were found in liver, lung and pelvis. We performed conservative therapy including right renal embolization. However, serum calcium levels continued to increase. Patient died from renal failure and pneumonia after 2 months, and autopsy was performed. Histological examination revealed infiltrative transitional cell carcinoma of the right kidney. PTH like peptide was measured 1 ng/gram wet tissue from the primary tumor and 16.6 ng/gram wet tissue from the metastatic liver tumor. PMID- 1927778 TI - Solitary pelvic kidney: an incidental case. AB - We report a case of solitary pelvic kidney. This uncommon condition was detected incidentally and diagnosed with intravenous pyelography (IVP), computed tomography (CT), and retrograde pyelography (RP). PMID- 1927779 TI - [Treatment with percutaneous nephrolithotripsy and dissolution for bilateral renal cystine calculi in an infant]. AB - A 20-month-old child was admitted to our hospital due to obstructive renal failure caused by cystine calculi. After recovering from the renal failure by bilateral percutaneous nephrostomy, pelvic irrigation with N-acetylcysteine was performed using a 12Fr. flexible double lumen catheter. In 2 weeks the calculus was reduced by 39% in size, then residual calculi were successfully removed by percutaneous nephrolithotripsy using 11.5Fr. rigid ureteroscope and postoperative irrigation with N-acetylcysteine. PMID- 1927780 TI - [A case of uretero-vaginal fistula with ureteral foreign body stone originated from the suture thread]. AB - A 32-year-old female was admitted to our hospital with the chief complaint of vaginal discharge of urine. She had undergone radical hysterectomy due to uterine cancer at another hospital by a gynecologic surgeon 5 years earlier. X-ray examination showed a stone-like shadow at the left ureter without hydronephrosis. She was diagnosed with ureterovaginal fistula with the left ureteral stone. Left ureterolithotomy and ureterovesiconeostomy was performed. The stone revealed a foreign body stone originating from the silk worm-gut which had penetrated accidentally the ureter when the vaginal wall was sutured at the previous surgery. Including our case, 15 cases of foreign body stones in the upper urinary tract were found in the Japanese literature and none of them were associated with ureterovaginal fistula. PMID- 1927781 TI - [A case of emphysematous cystitis with familial amyloidosis]. AB - This is a report of the thirteenth known case in Japan of emphysematous cystitis. A 70-year-old man visited our hospital because of pollakisuria and macrohematuria on November 21, 1989. The patient had been known to have familiar amyloid polyneuropathy for the previous 3 years. Urinalysis showed marked hematopyuria. The residual urine was 216 cc, and urine cultures yielded 10,000,000 colonies of Escherichia coli per ml. Laboratory studies revealed systemic inflammatory findings, but no diabetic change. A plain X-ray film of the abdomen and an excretory urogram (DIP) showed small linear and round gas collections in the bladder shadow. A CT scan revealed multiple gas locules within the bladder wall. A diagnosis of emphysematous cystitis was established. The patient was given antibiotics, and there was striking clinical improvement. Histological examination of the endoscopically obtained biopsy specimen of the bladder revealed amyloidosis. We believe that this patient had a cystitis emphysematosa precipitated neurogenic bladder due to amyloid polyneuropathy and amyloidosis of the bladder. PMID- 1927782 TI - [A case of advanced prostatic cancer presenting as inguinal mass]. AB - A 71-year-old man visited our hospital complaining of a nodule in the left inguinal region. Pathological and immunohistochemical examination of the prostate and the mass and clinical examination revealed a case of prostatic cancer with lymph node metastasis, stage D. Chemoendocrine therapy (diethylstilbestrol diphosphate, cisplatin, adriamycin and carboquone) was performed and the patient responded well. This case indicated the presence of an unusual prostatic cancer in which large non-regional superficial lymph node metastasis occurred. PMID- 1927783 TI - [A case of prostatic hyperplasia in a young male]. AB - Prostatic hyperplasia in young males is a very rare disease. A 28-year-old man was admitted to our hospital on June 24, 1989, with the chief complaints of intermittent macrohematuria and dysuria. Endoscopic examination revealed two papillary tumors in the prostatic urethra; no urinary bladder tumor was found. A transurethral resection was done for the urethral tumors. Pathological examination revealed prostatic hyperplasia. These lesions were considered ectopic prostatic tissue at first. However, imaging showed that this may in fact be prostatic hyperplasia of the apical region near the capsule. The post-operative course was uneventful and he is presently observed as an outpatient. This patient represents the seventh case reported in the literature. PMID- 1927784 TI - [A case of pathological dilation of seminal vesicle with high level of serum CA 19-9]. AB - A case of pathological dilation of seminal vesicle is presented. A 18-year-old male was admitted to our hospital with the complaints of gross hematuria and discomfort of the scrotum. IVP and abdominal CT scan revealed the left aplastic kidney, and ultrasound, vesiculography, and pelvic CT scan revealed markedly dilated bilateral seminal vesicles without filling defects. The level of serum CA19-9 was 390 u/ml, which was extremely high. After resection of dilated seminal vesicles, it returned to the normal range (37 u/ml). Sixty six cases of pathological dilation of seminal vesicle were collected from the Japanese literature. No cases showing a high level of serum CA19-9 have been reported in Japan. PMID- 1927785 TI - Testicular microlithiasis: sonographic features with pathologic correlation. PMID- 1927786 TI - Hemorrhage associated with pelvic fractures: causes, diagnosis, and emergent management. AB - The high risk of exsanguinating hemorrhage in patients with pelvic ring disruption demands aggressive, yet balanced orthopedic and angiographic management as soon as patients are admitted to the emergency department. We present a perspective of our experience in two trauma centers and propose a logical approach to early prediction, diagnosis, and management of hemorrhage associated with pelvic fractures. Our method is based on knowledge of pelvic anatomy and an understanding of the mechanisms of injury and their wounding capacity, given that the mechanism of injury determines the type of pelvic ring disruption and that the probability of arterial hemorrhage is--to a great extent- a function of the type of pelvic fracture. The risks of diagnostic peritoneal lavage and of excessive radiologic studies of noncritical injuries are emphasized. The principles guiding arterial embolization and the application of external fixators are discussed. PMID- 1927787 TI - MR imaging of the labral-capsular complex: normal variations. AB - Understanding the normal anatomy of the shoulder and its variations is important for the proper interpretation of MR images. This study was performed to describe variations in the normal labral-capsular complex as seen on MR images. MR images of 52 shoulders in 30 asymptomatic volunteers and 27 shoulders of symptomatic patients who had subsequent arthroscopy and/or reconstructive surgery were obtained with 1.5-T MR. The 52 scans of the asymptomatic group were reviewed by three radiologists in conference, and the assessment of labral shapes and capsular insertions was done by consensus. The 27 MR scans of the shoulders in the symptomatic group were reviewed by one radiologist before and after the asymptomatic cases were interpreted. Differences in these two interpretations were shown on receiver-operating-characteristic curves by using the results of subsequent arthroscopy and surgery as the gold standard. The anterior and posterior parts of the labra, respectively, varied in shape but showed several dominant features: triangular (45%, 73%), round (19%, 12%), cleaved (15%, 0%), notched (8%, 0%), flat (7%, 6%), and absent (6%, 8%). Most capsules inserted anteriorly on the labrum (47%) or glenoid rim (49%). All posterior insertions were on the labrum (100%). Intrinsic labral signal was noted on proton density weighted images, but never on T2-weighted images. Receiver-operating characteristic curves from interpretations of the symptomatic and clinical cases made before and after evaluation of the asymptomatic shoulders showed the interpretations improved considerably after scans of asymptomatic volunteers were studied. Our study reveals a wide variability in the MR appearance of the labral capsular complex in asymptomatic shoulders. PMID- 1927788 TI - Dialysis-related amyloid arthropathy: MR findings in four patients. AB - Dialysis-related amyloidosis is a recently recognized complication of long-term hemodialysis. It is caused by the deposition of a unique form of amyloid derived from circulating beta 2-microglobulin. This study describes the MR imaging characteristics in five articular sites of four symptomatic patients with biopsy proved (three patients) or clinically and radiographically suspected (one patient) dialysis-related amyloidosis. Three wrists, one knee, and one cervical spine were examined. The extent of osseous and soft-tissue involvement at each joint site was well shown by MR imaging. Lesions that were apparently intraosseous on conventional radiographs were shown to be caused by well-defined erosions that extended to the articular surface. The MR signal characteristics of the amyloid deposition were intermediate between those of fibrocartilage and muscle on all sequences, distinguishing the deposition from cellular lesions or those containing large amounts of water, such as inflammatory masses, acute or chronic synovitis, and brown tumors of hyperparathyroidism. The intraarticular masses were associated with a moderate joint effusion in the large joint imaged, and small effusions were present in the wrist. Use of a fat-suppression sequence enhanced visualization of amyloid deposits within the wrist of one patient but provided no additional information in the knee of a second patient. Our experience suggests that MR imaging is well suited to showing the extent and distribution of articular disease in dialysis-related amyloidosis. PMID- 1927789 TI - Hallux rigidus deformity: radiologic assessment. AB - Hallux rigidus (osteoarthritis leading to reduced motion) is one of the most common afflictions of the first metatarsophalangeal joint. The diagnosis is based on the presence of pain, specific physical findings, and certain radiologic features. In this essay, we illustrate the grades of radiologic changes, which are an integral part of the surgeon's preoperative evaluation, and show examples of the postoperative radiologic appearance. PMID- 1927790 TI - Skeletal lymphoma in a patient with Castleman disease. PMID- 1927791 TI - Drug-related complications in infants and children: imaging features. AB - Iatrogenic disorders continue to be an important cause of morbidity and mortality in infants and children. Most adverse drug reactions have no distinctive radiologic features. Of those with radiologic manifestations, it is usually impossible to differentiate iatrogenic disorders from their spontaneously occurring counterparts. However, certain iatrogenic disorders have distinctive imaging characteristics that allow their recognition in specific patient populations. This review considers a variety of drug-related disorders and phenomena that have been the subject of original articles in the English language literature since 1984. PMID- 1927792 TI - Sonography of the biliary tract in infants and children. AB - Diseases of the gallbladder and biliary system are particularly well suited for investigation with sonography. As such, sonography has completely supplanted oral cholecystography in the evaluation of these disorders. Because it is easy to perform and does not expose the patient to radiation or contrast agents, sonography is being used more often in children to diagnose disorders of the gallbladder and biliary tract. Many of the sonographic signs of these diseases (e.g., cholelithiasis, cholecystitis) are well established in adults and are the same in children. However, the circumstances under which these diseases occur and their different causal factors are different in children and adults. This article reviews the distinctive aspects of gallbladder-biliary tract disease in children, concentrating on the role that sonography plays in its evaluation and therapy. PMID- 1927793 TI - Perforation of the augmented urinary bladder in nine children and adolescents: importance of cystography. AB - Augmentation of the urinary bladder is a popular surgical procedure for increasing the capacity and lowering the intraluminal pressure in patients whose bladder is small, noncompliant, or has high pressure. Among 250 augmentations performed at our hospital, nine patients have had 16 episodes of postoperative extravasation of urine from their augmented bladder. Thirteen episodes were studied by fluoroscopically monitored contrast cystography, which was diagnostic in 12. One patient's perforation was noted during an unrelated operation and the other two died of peritonitis before cystography could be performed. Four episodes occurred early, within 3 weeks of surgery. All were at a surgical anastomosis and presumably represented incomplete healing. Each patient with an early episode of extravasation had a perforation later. Nine perforations occurred from 1.0 to 6.5 months after the augmentation. Of these, three occurred at an anastomosis and four occurred in the augmenting segment. The locations of two were never fully documented. Three perforations occurred late, from 2.5 to 6.0 years after surgery, and all were in the augmenting segment. Three of the nine patients died of complications associated with perforation. Perforation of the bladder is not rare and is a potentially fatal complication of augmentation. Whenever a patient who has undergone augmentation has signs or symptoms suggesting perforation, cystography can play a crucial role in diagnosis and should be performed without delay. PMID- 1927794 TI - MR angiography of vascular grafts in children. PMID- 1927795 TI - Proton MR spectroscopy in multiple sclerosis: value in establishing diagnosis, monitoring progression, and evaluating therapy. AB - MR imaging is currently the technique of choice for evaluating brain lesions in patients with multiple sclerosis (MS). In addition to MR imaging, proton MR spectroscopy has shown potential in diagnosing MS and monitoring the progression of treatment. Spatially localized proton spectroscopy has been used to evaluate changes in choline, creatine, N-acetyl aspartate (NAA), lipids, and lactate in MS patients and in animal models of MS. The main spectroscopic findings are a decrease in the NAA:creatine ratio and an increase in the choline:creatine ratio in brain regions that include plaques defined by MR imaging. Proton MR spectroscopy along with MR imaging may be helpful in distinguishing those early lesions that might respond to therapy from late irreversible lesions. Preliminary evidence suggests that although the proton spectra acquired from patients with various brain diseases are similar (high choline, low NAA), there are differences in other resonances (lipids, lactate, glutamate, inositol) that could potentially help in diagnosing MS. Changes in proton metabolites potentially can be used to differentiate between the different stages of the MS lesion (hyperacute and edematous lesions, demyelinated lesions, and subacute to chronic plaques). It is hypothesized that successful treatment of demyelination and neuronal damage will be accompanied by changes in the proton spectrum (high choline:creatine ratio will lower to normal values and low NAA:creatine values will rise to normal values). PMID- 1927796 TI - Sonography of the eye. AB - Real-time sonography of the eye is a technique that is rapidly performed and readily available in most sonography departments. It is less expensive than CT and MR imaging and, if necessary, may be performed at the patient's bedside. This essay demonstrates a few of the large number of clinical entities that may be successfully examined with this technique. PMID- 1927797 TI - A PC-based semiautomated reporting system. PMID- 1927798 TI - Understanding receiver-operating-characteristic curves: a graphic approach. PMID- 1927799 TI - Use of CT for evaluation of possible traumatic aortic injury. PMID- 1927800 TI - In vitro method for teaching percutaneous vascular catheterization. PMID- 1927801 TI - Subclavian vein and dialysis access planning. PMID- 1927802 TI - Outcome of sonography for deep venous thrombosis. PMID- 1927803 TI - Visualization of meniscofemoral ligaments on coronal MR of the knee. PMID- 1927804 TI - MR imaging of the knee in rheumatoid arthritis and other rheumatic diseases. PMID- 1927805 TI - Vascular erosion of a cervical neural foramen: diagnosis with MR angiography. PMID- 1927806 TI - Focal high signal on MR images of the midbrain. PMID- 1927807 TI - Disappearance of the basivertebral vein: a new MR imaging sign of bone marrow disease. PMID- 1927809 TI - Clarence Dally: an American pioneer. PMID- 1927808 TI - AIDS risk and risk reduction in the radiology department. AB - As the AIDS epidemic progresses, concern about the risk of occupational transmission of the causative organism, human immunodeficiency virus (HIV), is increasing. In this article, we summarize the risk of occupational acquisition of HIV in the health care setting and specify protocol and equipment that can reduce this risk in the radiology department. Accidental needle-stick injury is the most common form of exposure to infected blood, which is the only body fluid implicated to date in the occupational transmission of HIV. Prospective cohort studies demonstrate a 0.3-0.4% risk of infection for each needle-stick event. The most important instruction to health care workers that can reduce this risk is the following: Do not recap needles. Other risk-reduction measures include the adoption of universal precautions against transmission of infectious disease; sharp-instrument precautions; the use of protective garb to prevent skin and mucous membrane contamination when blood or bloody body fluid may splash; the availability of stable, puncture-resistant disposal containers for sharp instruments; the exclusion of breakable glass syringes; and the accessibility of resuscitation equipment in all rooms in order to avoid direct mouth-to-mouth contact. These and other measures discussed here are designed to prevent exposure of skin or mucous membrane to blood. If exposure does occur, the contaminated area should be washed immediately. A multicenter research protocol to evaluate the effectiveness of zidovudine (AZT) therapy in preventing seroconversion after exposure to HIV-contaminated blood recommends AZT therapy after massive exposure (e.g., injection of measurable quantities of blood) and endorses it for serious parenteral exposure (e.g., deep needle sticks). PMID- 1927810 TI - Radiologic assessment of impotence: angiography, sonography, cavernosography, and scintigraphy. AB - Recent advances in the understanding of erectile dysfunction have led to new treatments for vasculogenic impotence and a need for improved imaging techniques. Although much controversy still exists in this evolving field, we provide a review of the concepts and techniques currently used in cavernosography, sonography, scintigraphy, and angiography to evaluate the impotent patient. PMID- 1927811 TI - Percutaneous biopsy of skeletal lesions. AB - Percutaneous needle biopsy of lesions affecting the musculoskeletal system should be considered a routine radiologic procedure. Although relatively safe, the procedure requires expertise. An experienced radiologist and the cooperation of a skilled pathologist are essential. Consultation with the orthopedic surgeon is also important, especially when resection of the lesion is contemplated. Recent advances in imaging techniques and the availability of various cutting and trephine needles have made it easier to perform biopsies safely and accurately, even in difficult locations. The procedure obviates surgery in many instances and facilitates appropriate surgical planning in others. This review offers a pragmatic approach to percutaneous needle biopsy of skeletal lesions. It is hoped that more radiologists will be encouraged to undertake these valuable procedures. PMID- 1927812 TI - Defects of the interventricular septum of the heart: en face MR imaging in the oblique coronal plane. AB - MR imaging in the oblique coronal plane can provide an en face image of ventricular septal defects by visualizing the entire circumference of the defect. This pictorial essay illustrates various types of ventricular septal defects as seen on these images. PMID- 1927813 TI - Bronchopulmonary sequestration: dynamic, ultrafast, high-resolution CT evidence of air trapping. PMID- 1927814 TI - Bilateral bronchogenic cysts. PMID- 1927815 TI - The radiologic diagnosis of Barrett esophagus: importance of mucosal surface abnormalities on air-contrast barium studies. AB - Patients with Barrett esophagus are predisposed to the development of esophageal adenocarcinoma. Identification of these patients before this complication develops is essential. We prospectively made the diagnosis of Barrett esophagus on routine biphasic upper gastrointestinal series in nine patients in whom a mucosal surface pattern alteration was the only radiologic abnormality on the esophagogram. The diagnosis was confirmed by biopsy in eight patients and during surgery in one patient. Only a third of the patients had symptoms related to the esophagus. Two types of surface changes were noted. A reticular pattern was present in six cases and a villous pattern in five cases. Both patterns were noted in two patients. This series was obtained in a 5-year interval during which there were 15 additional patients with Barrett esophagus and corresponding esophagograms. None of these patients had normal results on esophagograms. Recognition of these subtle surface patterns, particularly in the absence of other reflux-induced abnormalities, may improve detection of Barrett esophagus and aid in the selection of patients for subsequent surveillance. PMID- 1927816 TI - Disseminated histoplasmosis: abdominal CT findings in 16 patients. AB - Since the onset of the AIDS epidemic, disseminated Histoplasma capsulatum infection has been reported with much greater frequency in both endemic and nonendemic areas. Abdominal CT scans of 16 patients with disseminated histoplasmosis were reviewed retrospectively to identify radiologic features of this disease. The diagnosis was confirmed by autopsy (three patients), bone marrow biopsy (10 patients), lymph node biopsy (three patients), bronchoscopic biopsy (three patients), liver biopsy (two patients), and/or colonoscopic biopsy (one patient). Fourteen patients had serologic evidence of human immunodeficiency virus infection. Disseminated histoplasmosis was either the only initial manifestation of AIDS (seven patients) or was accompanied simultaneously by cytomegalovirus infection (four patients), or Kaposi sarcoma, Toxoplasma encephalitis, or cryptosporidiosis (one patient each). Abdominal CT findings included hepatomegaly (63%); splenomegaly (38%); diffuse splenic hypottenuation (19%); bilateral adrenal enlargement or hypoattenuating masses (13%); and enlarged lymph nodes with homogeneous soft-tissue density (44%), diffuse or central low density (13%), or both (19%). Histoplasmosis should be included in the differential diagnosis when abdominal CT scans show such nonspecific findings as hepatomegaly, splenomegaly, enlarged soft-tissue-density or hypoattenuating lymph nodes, or adrenal enlargement or masses in an immunodeficient patient. An uncommon but possibly specific CT finding in histoplasmosis is diffuse splenic hypoattenuation. PMID- 1927817 TI - Primary sclerosing cholangitis: value of cholangiography in determining the prognosis. AB - We studied cholangiograms in 129 patients with primary sclerosing cholangitis (PSC) to determine if there was a correlation between any of the findings and the prognosis of the disease. The grade, length, and extent of strictures, the degree of bile duct dilatation, and the distribution of lesions were evaluated. Survival curves were generated to test the association of these radiologic signs with subsequent survival. High-grade intrahepatic duct strictures (greater than 75% narrowing) were associated with a 19% decrease in 3-year survival (p = .05) compared with lower-grade strictures. Diffuse intrahepatic strictures (involving greater than 25% of the ducts) were associated with a 16% decrease in 3-year survival (p = .012) compared with localized strictures. Statistically insignificant (p greater than .05) but measurable decreases in survival were observed with high-grade extrahepatic duct strictures, diffuse involvement of the extrahepatic ducts, long confluent strictures anywhere in the biliary tree, and marked dilatation of the intrahepatic ducts. In general, intrahepatic duct disease was found to have greater prognostic significance than extrahepatic duct disease. High-grade strictures and diffuse strictures of the intrahepatic ducts were found to be indicators of a poor prognosis in PSC and were more predictive of a poor prognosis than was extrahepatic duct disease. PMID- 1927818 TI - Color Doppler sonography in a case of splenic hemangioma: value of compressing the tumor. PMID- 1927819 TI - Transfemoral venous catheterization through inferior vena caval filters: results in seven cases. AB - Use of the transfemoral route for venous catheterization has been considered contraindicated in patients with inferior vena caval (IVC) filters. The transjugular route has been used instead in such patients when subsequent diagnostic or therapeutic procedures are required. Many radiologists, however, are more accustomed to the transfemoral approach, and may not find the transjugular route a desirable alternative. We describe seven patients with previously placed IVC filters in whom the transfemoral route was used to perform pulmonary arteriography (five patients) or to place additional IVC filters (two patients). After venographic confirmation of caval patency, filters were catheterized under fluoroscopic control and the procedures were performed. All procedures were technically successful; no complications occurred. We believe the transfemoral route to be a safe and feasible approach for performing venous procedures in selected patients with IVC filters, obviating the less familiar and potentially more hazardous transjugular approach. PMID- 1927820 TI - Multiple intrahepatic portohepatic venous shunts: treatment with steel-coil embolization. PMID- 1927821 TI - Edith Cavell. PMID- 1927822 TI - Detection of renal stones with real-time sonography: effect of transducers and scanning parameters. AB - Three experiments with a variety of transducers and scanning parameters were designed to investigate if renal stones could be detected with greater certainty by using particular transducers or scanning parameters. First, the lateral resolution, derived from the -6-dB size of the beam profile, was measured at various depths for five transducers commonly used for renal sonography. Second, an in vitro test object was constructed from bovine liver, porcine kidneys, and two renal calculi to access gray-scale map effects on shadow visibility before and after storage in the digital scan converter. The third experiment combined 15 lithotripsy patients with known renal stones with 16 patients in whom the results of renal sonography and other radiographic procedures suggested renal calculi. The group of 15 patients was scanned several times with the transducers and gray scale maps studied earlier, and the group of 16 patients was scanned only with one transducer and one gray-scale map. On radiographs, 12 of the 16 patients did not have renal calculi. Sonograms of the test object showed that low-contrast images were best for detection of posterior shadows. Three radiologists interpreted the 31 sonograms with a sensitivity of 81% and a specificity of 86% for detecting renal stones. For the 15 cases of renal stones scanned with a variety of transducers, the three radiologists found that annular-array transducers depicted stone shadowing with less ambiguity than mechanical sector transducers did 81% of the time. PMID- 1927823 TI - Imaging of the renal arteries: value of MR angiography. AB - We compared the efficacy of MR angiography with that of conventional angiography for visualizing the renal arteries and detecting renovascular disease. Thirty three MR angiographic studies, consisting of axial two-dimensional (2-D) phase contrast, coronal 2-D phase-contrast, and coronal 2-D time-of-flight acquisitions, were performed within 48 hr of conventional arteriography. The studies were done to evaluate possible renovascular hypertension (n = 25) or potential donor nephrectomy (n = 8). The three MR image sets were interpreted independently, in random order by three observers, with regard to the number of renal arteries, degree of vessel visualization, arteriovenous overlap, and presence of renovascular disease. A fourth interpretation was based on the combined axial and coronal phase-contrast image sets. Evaluation was limited to the proximal 35 mm of each renal artery. Renal artery visualization and detection of renovascular disease were more complete with coronal phase-contrast (80% sensitivity, 91% specificity) than with time-of-flight (53% sensitivity, 97% specificity) images. Combined axial and coronal phase-contrast images permitted visualization of the proximal 35 mm of all dominant renal arteries and detection of 13 of 15 stenoses (87% sensitivity, 97% specificity). Our data suggest that biplanar MR angiography has considerable potential as a noninvasive screening technique for the evaluation of renovascular disease. PMID- 1927824 TI - Arteriovenous malformations of the kidneys: diagnosis and follow-up with color Doppler sonography in six patients. AB - We performed color Doppler sonography in six patients with arteriovenous malformations of the kidneys. The diagnosis was established by angiography in all patients. Color Doppler sonograms were obtained at a large Doppler frequency shift range (55 cm/sec of maximal average flow velocity at zero Doppler angle) to depict high-velocity blood flow in the malformation. In all patients, the malformations were seen as focal areas of flow, portrayed as a mixing of lighter colors. These were reflected by a rapid flow rate and marked tortuosity of the vessels. The sonograms showed a small peripheral malformation that was indistinct on selective renal angiography. However, flow in normal vessels grouped in the hilum obscured lighter-color flow of a small central malformation. In three patients who had total or partial ablation of the malformations with alcohol, follow-up color Doppler sonograms showed that the focal areas of flow, represented as mixing of lighter colors, disappeared or became smaller. This study shows that color Doppler sonography is a useful noninvasive procedure for diagnosing arteriovenous malformations of the kidney. PMID- 1927825 TI - Nonobstructing periureteric venous ring: diagnosis with conventional and three dimensional reconstruction CT. PMID- 1927827 TI - Senate passes amendments on HIV/AIDS. PMID- 1927828 TI - Hair follicle mites in humans. PMID- 1927826 TI - Transitional cell carcinoma of the bladder: patterns of recurrence after cystectomy as determined by CT. AB - CT scans have been recommended for examination of patients at risk for recurrent transitional cell carcinoma after cystectomy. For CT to be useful in this regard, the location and type of recurrences must be known, so that appropriate scans can be made. Therefore, we retrospectively studied CT scans in 27 postcystectomy patients with recurrent transitional cell carcinoma of the bladder to identify the type and location of the recurrent disease. Recurrence was documented by biopsy in 18 patients and by progression of disease shown on serial CT scans in nine patients. All 27 patients had pelvic CT, and 23 had concomitant abdominal CT. Tumor recurred at the cystectomy site in 10 (37%) of 27 patients, pelvic adenopathy was present in 18 (67%) of 27 patients, and retroperitoneal adenopathy was present in 13 (57%) of 23 patients. Tumor recurrence at the cystectomy site was associated with pelvic adenopathy in seven of 10 patients, and the cystectomy site was the solitary site of disease in the remaining three patients. Conversely, in 11 of 18 patients with pelvic adenopathy no recurrence was seen at the cystectomy site. Combined retroperitoneal and pelvic adenopathy was identified in 11 of 23 patients, but two patients had retroperitoneal lymphadenopathy as their only site of recurrence. Hepatic metastases were seen in seven (30%) of 23 patients; six of these seven patients had metastases elsewhere. In four of five patients in whom underestimation of recurrent disease occurred, the deep pelvis and/or deep perineal space were involved. Our results show that the pelvis is the most common site for recurrence. Cystectomy site or retroperitoneal nodal recurrences are usually accompanied by pelvic adenopathy, but the converse is not as common. Our findings of deep perineal and isolated abdominal recurrences indicate that proper protocol for CT follow-up of the postcystectomy patient should include abdominal scans and scans through the perineum. PMID- 1927829 TI - House calls and alprazolam for agoraphobia. PMID- 1927830 TI - The cervical cap. PMID- 1927831 TI - Metoprolol-induced delirium perpetuated by propafenone. PMID- 1927832 TI - Tuberculosis. PMID- 1927833 TI - Encouraging patients to use seat belts. PMID- 1927834 TI - Injections of joints and soft tissue: Part I. General guidelines. AB - Joint and soft tissue injections may be used therapeutically and as diagnostic tests to differentiate various pain syndromes. With proper patient selection and the use of appropriate injection techniques, morbidity can be less than that seen with nonsteroidal anti-inflammatory drug therapy. Family physicians can readily learn aspiration and injection techniques and should be able to perform injections of most anatomic sites. PMID- 1927835 TI - Clinical significance and treatment of xanthomas. AB - Xanthomas are important clinical manifestations of a variety of disorders, including lipoprotein abnormalities, hypothyroidism, diabetes and certain forms of cancer. Many patients with these lesions are also at risk for premature atherosclerosis. Family physicians are often the first to recognize xanthomas. Early detection and identification of the lesions leads to appropriate diagnosis and treatment of the related diseases. PMID- 1927836 TI - New concepts in bacterial vaginosis. AB - Bacterial vaginosis is a polymicrobial, superficial infection caused by an increase in anaerobic bacteria and a concomitant decrease in lactobacilli. Diagnosis is based on the presence of three of the following findings: a homogeneous vaginal discharge; an amine odor released by the addition of 10 percent potassium hydroxide; the presence of clue cells on wet mount; the absence of lactobacilli on wet mount, and an increase in the pH of vaginal secretions to more than 4.7. Oral metronidazole is the drug of choice for the treatment of bacterial vaginosis, but clindamycin is an effective alternative. PMID- 1927837 TI - Abuse of skeletal muscle relaxants. AB - Centrally acting skeletal muscle relaxants are potential drugs of abuse. Although skeletal muscle relaxants are occasionally the primary drug of abuse, they are often used along with other central nervous system depressants, such as narcotics or alcohol. The major toxic effects are respiratory depression and coma. For the most part, the abuse problem is initiated and sustained iatrogenically. Physicians should be aware of the abuse potential of skeletal muscle relaxants. PMID- 1927838 TI - Bulimia nervosa: the role of the family physician. AB - Bulimia nervosa is an eating disorder characterized by binge eating and purging. The disorder is estimated to occur in up to 5 percent of young women. Despite severe psychosocial impairment and potentially serious medical complications, patients do not usually reveal their bulimic behavior to a physician unless directly asked. Promising treatments include cognitive-behavioral psychotherapy and antidepressant medications. PMID- 1927839 TI - Depressive disorders in older medical inpatients. AB - Symptoms of depression that are temporary or caused by physical illness can be difficult to differentiate from those that represent a depressive disorder. A diagnosis of depressive disorder depends on the underlying cause, and on the nature, severity and duration of symptoms. Management involves accurate diagnosis and treatment of medical illness, practical interventions to resolve concurrent family, social and economic stressors, and emotional support. Cognitive, behavioral and brief psychodynamic therapies may be helpful in selected cases. Antidepressants and electroconvulsive therapy have a role in the treatment of severe or persistent depression associated with suicidal behavior, marked psychomotor retardation, starvation or other life-threatening symptoms. Suicidal thoughts are frequent in older patients with concurrent major depression and chronic illness, and measures to ensure patient safety are a priority. PMID- 1927840 TI - Parathyroid hyperplasia as a cause of recurrent hyperparathyroidism. AB - Parathyroid hyperplasia is second only to adenoma as the most common cause of hyperparathyroidism. Symptoms are most likely to result from elevated serum calcium levels. Symptoms include nephrocalcinosis and nephrolithiasis. Studies that may help confirm a suspected diagnosis include ultrasonography, computed tomography, radionuclide scanning with thallium and/or technetium, and magnetic resonance imaging. Surgical treatment consists of excision of all but part of one parathyroid gland if all of the glands are enlarged. PMID- 1927841 TI - Advising parents on toilet training. AB - Toilet training is a potential source of anxiety for parents and children. The proper approach to toilet training involves an assessment of the readiness of both the child and the parents. Parents should have a realistic idea of the chances of success, and they must be patient and supportive. The majority of children are completely toilet trained by two and one-half years of age. Physicians should initiate discussions about toilet training with parents when a child is 12 to 18 months of age. PMID- 1927842 TI - Adolescent sexuality issues in office practice. AB - Sexuality is an important aspect of development during adolescence. A knowledge of the sexual issues relevant to each stage of adolescence will help the physician address sexual issues with adolescent patients. The ability to identify and communicate with adolescents who may be at high risk of premature sexual activity is particularly important since sexual intercourse at an early age can have serious short- and long-term consequences. A nonjudgmental manner, an emphasis on confidentiality and an honest appraisal of the implications of early sexual activity will enhance discussions about sexual issues with adolescents. PMID- 1927843 TI - Preoperative screening for perioperative cardiac risk. AB - Preoperative screening for potential cardiac complications is crucial in making rational decisions about surgery. A number of classification schemes are available to aid the primary care physician in assessing a patient's perioperative cardiac risk. In general, these schemes enable the physician to place patients in low-risk, moderate-risk and high-risk categories. Patients at low risk can often be safely referred for surgery with minimal preoperative evaluation, while those at potentially high risk frequently need further assessment and medical or surgical treatment of cardiac disease prior to surgery. The classification schemes are most accurate in identifying patients at high risk for perioperative cardiac complications. However, patients with silent underlying cardiac disease are often underclassified with respect to potential risk. For those patients, accurate prediction of perioperative cardiac complications can be challenging. PMID- 1927844 TI - Motor vehicle crash injury: mechanisms and prevention. AB - Nearly 50,000 persons are killed and 5 million are injured on the nation's highways each year. Motor vehicle injuries produce enormous costs for society. The use of motor vehicle safety restraints can substantially reduce death, disabilities and expenses associated with crashes. Primary care physicians have an important role in educating patients about the benefits of correct and consistent use of safety restraints. PMID- 1927845 TI - Bowen's disease: squamous cell carcinoma in situ. AB - Bowen's disease is a premalignant condition that clinically presents as an asymptomatic, scaly or crusted plaque on the skin. Since the morphology of the lesions can mimic that of other cutaneous disorders, Bowen's disease is often not recognized initially. The diagnosis of Bowen's disease should be considered and a skin biopsy performed when a patient presents with a persistent cutaneous lesion that is of uncertain diagnosis or that has been previously diagnosed as "atypical" or "steroid-nonresponsive" dermatitis. PMID- 1927846 TI - The sick employee: medical certificates and the primary care physician. AB - A medical certificate is the principal way physicians communicate an employee's illness or injury to the employer. The employer is entitled to nonspecific information as to whether or not the physician considers the release from work to be legitimate and whether the employee has any medical problems that might interfere with job performance or make the employee a health risk to self or to others on the job. Specific information about diagnosis is only required when an injury or illness is related to workers' compensation. The medical certificate should describe when the examination took place, should specify the period of time that the employee is unable to work and should designate when and under what conditions the employee may return to work. PMID- 1927847 TI - Thrombolysis for pulmonary embolism. AB - More than 10 years ago, thrombolytic therapy with urokinase and streptokinase for pulmonary embolism was found to have considerable advantages over standard heparin therapy. After the introduction of alteplase, a recombinant tissue plasminogen activator, further studies confirmed this benefit. However, thrombolytic therapy for pulmonary embolism has not gained universal acceptance, even though it now has U.S. Food and Drug Administration approval. Clear advantages of thrombolytic therapy over conventional heparin therapy are improved pulmonary capillary blood volume, accelerated clot lysis and accelerated pulmonary perfusion. Earlier reversal of right-sided heart failure, a lower incidence of recurrent pulmonary embolism, a reduced risk of chronic pulmonary hypertension and reduced mortality have been claimed as advantages, but these have not been adequately proved. A recent survey suggests that about half of all patients with pulmonary embolism are potential candidates for thrombolytic therapy. In a subset of patients with hemodynamic compromise, thrombolysis has definite advantages over heparin therapy. PMID- 1927848 TI - ACIP issues influenza prevention guidelines. PMID- 1927849 TI - AIDS definition updated. PMID- 1927850 TI - The future of primary care in America. PMID- 1927851 TI - Results of electrophysiologic testing and long-term prognosis in patients with coronary artery disease and aborted sudden death. AB - The purpose of this study was to evaluate the results of electrophysiologic testing and the long-term prognosis of 56 patients with coronary artery disease who presented with aborted sudden death unrelated to acute myocardial infarction. The mean age of the patients was 62 +/- 8 years (+/- standard deviation) and 48 were men. The mean left ventricular ejection fraction was 0.34 +/- 0.16. During the baseline electrophysiology test, sustained monomorphic ventricular tachycardia (VT) was inducible in 22 patients who then underwent electropharmacologic testing: 11 patients were treated with antiarrhythmic drugs that suppressed the induction of VT or resulted in the VT becoming hemodynamically stable; 10 patients who failed drug testing received an automatic implantable cardioverter/defibrillator (AICD); one patient underwent endocardial resection. Among 34 patients who did not have inducible sustained VT, a precipitant of cardiac arrest (severe ischemia, proarrhythmia) was identified and was corrected in 9 of 34. An AICD was recommended in the remaining 25 patients; however, nine patients refused and were treated empirically with antiarrhythmic drugs. The mean follow-up was 22 +/- 12 months. The 2-year actuarial incidence of sudden death was 31% in patients who were treated with drugs based on the results of electropharmacologic testing, 26% in patients who were treated with antiarrhythmic drugs on an empiric basis, 0% among patients in whom a correctable etiology for the cardiac arrest was identified, and 9% among patients who underwent implantation of an AICD. The 3-year actuarial incidence of sudden death among the 20 patients treated with antiarrhythmic drugs was 53%, compared with 9% among the 26 patients who underwent AICD implantation (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927852 TI - Prospective, double-blind, placebo-controlled trial of low-dose amiodarone in patients with severe heart failure and asymptomatic frequent ventricular ectopy. AB - Sudden cardiac death is a common cause of mortality in patients with congestive heart failure. To determine if low-dose amiodarone could reduce sudden death among these patients, a prospective, placebo-controlled, double-blind pilot trial was conducted. One hundred one patients with ejection fractions less than 30%, New York Heart Association class III or IV symptoms, and frequent but asymptomatic spontaneous ventricular ectopy (Lown class II to V) were randomly assigned to treatment with low-dose amiodarone (400 mg/day for 4 weeks and then 200 mg/day) or placebo. Mean follow-up was 357 days (range 4 to 1009 days). Side effects were infrequent and there was no difference in the incidence of side effects between the treatment groups. The frequency of spontaneous ventricular ectopy in the group receiving amiodarone fell from 4992 +/- 1240 beats/24 hours at baseline to 1135 +/- 494 beats/24 hours after 1 month of treatment (p = 0.02) and remained low after 6 months, while there was no change in ventricular ectopy among the patients receiving placebo. Despite the reduction in ectopy, there was no improvement in mortality or decrease in the incidence of sudden death. One year mortality by Kaplan-Meier analysis was 28% in the group receiving amiodarone and 19% in the group receiving placebo (p = NS). One-year mortality in patients with greater than 75% reduction in ventricular ectopy after 1 month of treatment was 31% versus 17% in patients with less than or equal to 75% ectopic suppression (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927853 TI - Oral propafenone therapy for children with arrhythmias: efficacy and adverse effects in midterm follow-up. AB - The use of oral propafenone was assessed in 57 children. Mean age was 4.8 +/- 5.2 years (range 1 day to 17 years). Twenty-three patients were less than 1 year of age (40%) and 10 were less than 1 month of age (18%). Arrhythmias included supraventricular tachycardia in 32 patients (57%), atrial flutter in six (10%), and ventricular tachycardia in 19 (33%). Cardiac diagnoses included: an otherwise normal heart in 30 (53%); unoperated congenital heart defect in 11 (19%); cardiomyopathy in nine (16%); and an operated congenital heart defect in seven (12%). Mean dose of propafenone was 13.1 mg/kg/day (range 8 to 15). Success (assessed by relief of symptoms and serial 24-hour ECGs) was achieved in 16 of 32 patients with supraventricular tachycardia (50%), three of six with atrial flutter (50%), and 8 of 19 with ventricular tachycardia (42%). Drug efficacy in patients with and without organic heart disease was 30% (8 of 27) and 63% (19 of 30), respectively (p less than 0.05). Mean duration of therapy in patients in whom the drug was effective was 22.9 +/- 13.2 months (range 6 to 60). Growth was unimpaired in all patients. A neonate with nonsustained monomorphic ventricular tachycardia had sustained ventricular tachycardia during the second day of propafenone therapy at a dose of 13 mg/kg/day. Sustained ventricular tachycardia disappeared when the drug was discontinued. Another patient had an asymptomatic and transient increase in the glutamic pyruvic transaminase level. No adverse hemodynamic effects were observed. In conclusion, propafenone is an effective antiarrhythmic drug in children with normal hearts; it is less effective in patients with heart disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927854 TI - Assessment of right ventricular diastolic and systolic function in patients with dilated cardiomyopathy using cine magnetic resonance imaging. AB - Cine magnetic resonance imaging (MRI) can provide clear endocardial margins of the entire right ventricle, and Simpson's algorithm can be applied to obtain the volumes at multiple phases of the cardiac cycle. Time-volume curves of the right ventricle were obtained by using cine MRI in 10 patients with dilated cardiomyopathy (DCM) and eight normal volunteers to assess right ventricular function. There were no significant differences in volumes and ejection fraction of the right ventricle between the group with DCM and the normal group. In the group with DCM the time to peak filling rate was increased (p less than 0.05) and the filling fraction was decreased (p less than 0.01). In the patients with DCM cine MRI demonstrated normal volumes and ejection fraction of the right ventricle in contradistinction to the marked increase in volumes and the decrease in ejection fraction of the left ventricle; with the use of time-volume curves of the right ventricle, impairment of diastolic function of the right ventricle was demonstrated. PMID- 1927855 TI - Measurement of left ventricular contractility using transesophageal echocardiography in patients undergoing coronary artery bypass grafting. The Study of Perioperative Ischemia (SPI) Research Group. AB - Optimal assessment of left ventricular function requires the use of load independent indices of myocardial contractility, which often are difficult to obtain in patients undergoing coronary artery bypass graft (CABG) surgery. We have investigated whether the relation between left ventricular end-systolic stress (ESS) (derived from high-fidelity intraventricular pressure measurements and transesophageal-derived wall thickness) and end-systolic area (ESA) (derived from transesophageal echocardiography [TEE]) could provide a load-independent index of left ventricular function. We studied seven men undergoing coronary revascularization. Multiple data points at varied loading conditions were generated for each patient by infusions of sodium nitroprusside and phenylephrine during the period immediately after induction of general anesthesia and preceding surgical incision. While peak systolic blood pressure was pharmacologically altered between 78 and 204 mm Hg, the correlations between ESS and ESA were excellent for all patients (range r = 0.90 to 0.99). Additionally, the slopes of these relations showed a close correlation to their respective baseline thermodilution cardiac indices (r = 0.85, p = 0.02). Appropriate shifts of the ESS/ESA relationships were documented during postextrasystolic potentiation. The authors conclude that the left ventricular ESS/ESA correlation, derived using TEE and intraventricular pressure measurements, may provide a load-independent index of left ventricular inotropic state in patients undergoing CABG surgery. PMID- 1927856 TI - The effects of regurgitant orifice size, chamber compliance, and systemic vascular resistance on aortic regurgitant velocity slope and pressure half-time. AB - The determinants of the aortic regurgitant velocity profile have been investigated using computer and in vitro simulations in which regurgitant orifice area, ventricular and aortic compliance, and systemic vascular resistance could be independently varied. In the study, regurgitant fraction was altered, either by changing the size of the regurgitant orifice or by holding the regurgitant orifice constant and changing chamber compliance or systemic vascular resistance. Upon increasing regurgitant fraction by increasing the size of the regurgitant orifice, the slope got steeper and the pressure half-time shortened, the response anticipated in current clinical practice. However, when the regurgitant orifice was kept constant and regurgitation fraction was increased by increasing the systemic vascular resistance or by increasing the compliance of the left ventricle, slope became less steep and pressure half-time lengthened. Multivariate analysis was used to quantify the relationship of regurgitant fraction to slope and pressure half-time. When orifice area was allowed to vary, slope was related directly (multiple r = 0.78, p less than 0.001) and half-time was related inversely (multiple r = 0.66, p less than 0.001) to regurgitant fraction. With the orifice area fixed, however, directionally opposite responses were seen; slope varied inversely (multiple r = 0.87, p less than 0.001), whereas half-time varied directly (multiple r = 0.88, p less than 0.001) with regurgitant fraction. This study suggests that the utility of the slope and pressure half time of the regurgitant velocity tracing in clinical practice relates to their ability to discriminate regurgitant orifices of differing sizes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927857 TI - Pathologic and angiographic correlations of transesophageal echocardiography in prosthetic heart valve dysfunction. AB - To determine the diagnostic accuracy of transesophageal echocardiography (TEE) in prosthetic valve dysfunction, the pathologic and/or angiographic data from 37 valves were compared with that obtained by transesophageal and transthoracic echocardiography. Of the 21 prostheses with severe regurgitation, TEE identified all 14 mitral, the five aortic, and one of the two tricuspid valves; on the other hand transthoracic echocardiography identified 2 of the 14 mitral, the five aortic, and one of the two tricuspid valves. Of the 10 prostheses with flail cusp(s), nine (90%) were correctly identified by TEE and four (40%) were correctly identified by transthoracic echocardiography. All five prostheses with paravalvular regurgitation were detected through the esophageal window and one detected through the precordial window. TEE was unable to document the two prosthetic aortic stenoses, whereas the transthoracic examination correctly quantified the gradient in one but underestimated it in the other case. Seven patients underwent valve replacement on the basis of the clinical and TEE information alone. In assessing cause, origin, and severity of prosthetic mitral regurgitation, TEE is the method of choice. In selected cases, TEE can avoid angiography and facilitate optimal timing of reoperation. In selected aortic and tricuspid dysfunction, TEE may provide additional morphologic, but limited hemodynamic information. PMID- 1927858 TI - Potential diagnosis of hemodynamic abnormalities in patent ductus arteriosus by cine magnetic resonance imaging. AB - Cine magnetic resonance imaging was performed in 11 patients with communication between systemic and pulmonary circulation. In five patients with uncomplicated patent ductus arteriosus (PDA), ductus arteriosus was delineated by a persistent band of low signal intensity, whereas in two patients who also had severe pulmonary hypertension the signal intensity was varied. Two separate low signal intensities in the main pulmonary artery and the descending aorta were each uniformly recorded in the five patients with uncomplicated PDA, consistent with continuous left-to-right shunt and turbulent flow acceleration, respectively. In one of the patients with severe pulmonary hypertension but not Eisenmenger's syndrome, the areas of low signal intensity from left-to-right shunt and turbulent flow acceleration diminished. In the patient with Eisenmenger's PDA the right-to-left shunt was also characterized by an area of low signal intensity but with a reversal in direction. Cine MR imaging has the potential to be a noninvasive and supplemental method for evaluating PDA. PMID- 1927859 TI - Cardiorespiratory exercise capacity after surgical closure of atrial septal defect is influenced by the age at surgery. AB - To study the influence of age at the time of the operation on long-term functional performance in children undergoing surgery for atrial septal defect (ASD) of the secundum type, exercise tolerance was assessed in 24 patients and values were compared with those of normal subjects. Patients were divided into two groups: 11 patients had surgery before the age of 5 years (group 1) and 13 patients had surgery at a later age (group 2). There were no significant differences between groups 1 and 2 with regard to the pulmonary-to-systemic flow ratio, pulmonary artery pressure, and the interval between surgery and exercise testing. Performance capacity was assessed by determination of the ventilatory threshold during submaximal exercise. The mean value for the ventilatory threshold in group 1 was normal (99.4 +/- 15.1% of the age-predicted normal value). In the children who were more than 5 years of age at the time of the operation, the ventilatory threshold was below normal (84.5 +/- 10.9% of the age predicted normal value). Furthermore, in group 2 more patients (77%) had values that were below normal (below the 95% confidence limit of the age-predicted normal value) compared with group 1 (27%). It is concluded that functional performance capacity is better when surgical closure of ASD is performed in early childhood and before the age of 5 years rather than at a later age. PMID- 1927860 TI - Restrictive hemodynamic patterns after cardiac transplantation: relationship to histologic signs of rejection. AB - Hemodynamic and echocardiographic data from 33 consecutive patients undergoing cardiac transplantation were correlated with endomyocardial biopsy results to determine whether reversible restrictive hemodynamics accompany histologic evidence of transplant rejection. During the study period 251 biopsy specimens were obtained during periods of no histologic evidence of transplant rejection and 52 episodes of mild, 20 episodes of moderate, and one episode of severe rejection. Right atrial mean pressure increased significantly during episodes of moderate transplant rejection (9.9 +/- 6.2 mm Hg, p less than 0.001) compared with pressures obtained during periods when there was no evidence of rejection (4.6 +/- 3.2 mm Hg), mild rejection (5.8 +/- 3.9 mm Hg), or resolving rejection (4.3 +/- 3.4 mm Hg). Y descent was elevated during moderate rejection (9.6 +/- 4.2 mm Hg, p less than 0.001) compared with pressures during episodes of no rejection (5.6 +/- 2.5 mm Hg), mild rejection (6.6 +/- 2.7 mm Hg), and resolving rejection (5.8 +/- 3.1 mm Hg) and showed a wave morphology consistent with a restrictive hemodynamic pattern. Pulmonary capillary wedge pressure was increased during moderate rejection (14.4 +/- 6.4 mm Hg) when compared with pressures obtained during episodes of no rejection (10.2 +/- 5.8 mm Hg) or resolving rejection (10.2 +/- 5.4 mm Hg) (p less than 0.02). Sensitivity for a right atrial mean pressure of 11 mm Hg indicating moderate rejection was 41% with a specificity of 96%. Sensitivity for Y descent (greater than or equal to 10 mm Hg) was 52% and specificity was 94%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927861 TI - Factors influencing transmitral flow velocity in normal and hypertensive subjects. AB - Transmitral flow velocity and its determinants were examined with Doppler echocardiography in 53 hypertensive and 32 age-matched healthy normotensive men. Early and late maximal transmitral velocity, and early and late flow velocity integral were evaluated. In comparison with normal subjects, hypertensive patients were characterized by decreased maximal early velocity (66.3 +/- 12.3 versus 72.3 +/- 11.5 cm/sec, p less than 0.05), normalized early flow integral (67 +/- 7% versus 73 +/- 5%, p less than 0.001), increased maximal late flow velocity (45 +/- 10 cm/sec, p less than 0.001), and normalized late flow integral (29 +/- 7% versus 21 +/- 5%, p less than 0.001). Abnormally high late transmitral flow was found in 47% of the hypertensive group. Multiple regression analysis revealed that in normal subjects transmitral flow indexes were determined by age, relative wall thickness, and systolic blood pressure, but not by heart rate. A strong relationship of Doppler transmitral flow indexes with age was confirmed in hypertensive patients; however, relative wall thickness influenced transmitral flow velocity only weakly and systolic blood pressure did not affect transmitral flow. Left ventricular mass and diastolic blood pressure did not influence mitral filling velocity in either group. The altered pattern of mitral inflow found in a large number of hypertensive subjects is not related to elevated arterial blood pressure or to altered left ventricular geometry. PMID- 1927863 TI - Contrast agents for cardiac catheterization: conceptions and misconceptions. AB - Ionic and nonionic contrast materials are similarly efficacious in providing excellent images with minimal risk to the patient. In comparison with ionic media, the nonionic agents produce minor alterations in intracardiac and peripheral pressures as well as in electrocardiographic intervals and morphology. In addition, nonionic media are less often associated with undesirable symptoms, such as flushing and vomiting. At the same time, ionic and nonionic media are accompanied by a similar incidence of nephrotoxicity, serious arrhythmias, and death. Finally, nonionic contrast material is substantially more expensive than ionic media. In light of this marked difference in cost, one could argue that nonionic media should be reserved for "high-risk" patients, that is, those with a history of a serious adverse reaction to ionic contrast media and those in whom contrast-induced hypotension would be particularly deleterious. PMID- 1927862 TI - Effects of caffeine on pressor regulation during rest and exercise in men at risk for hypertension. AB - Caffeine-induced blood pressure elevations are well documented in habitual consumers, occurring through both vasoconstrictive and cardiostimulatory actions. Whether caffeine hinders pressor regulation during exercise has been uncertain, particularly in those at risk for hypertension. Thus effects of caffeine versus placebo were studied during supine bicycle exercise in healthy men (ages 20 to 35). Hypertension risk was defined during screening: high risk (HRISK) = 135 to 154/85 to 94 mm Hg plus parental hypertension (n = 20); low risk (LRISK) = less than or equal to 132/84 mm Hg and no parental hypertension (n = 14). Exaggerated pressor responses (greater than or equal to 230/100 mm Hg) seen during exercise after placebo identified a subgroup of seven HRISKs indistinguishable at rest from the remaining HRISK men. This subgroup showed a larger resting diastolic response to caffeine (p less than 0.05) than LRISKs and other HRISKs. Compared with placebo, caffeine increased the number of LRISK (0% to 36%) and HRISK (35% to 50%) men reaching abnormal exercise blood pressures, and blunted normal increments in cardiac index at higher workloads among HRISK men (p = 0.05). Thus restriction of caffeine before exercise might benefit persons with either risk for hypertension or unusual sensitivity to caffeine. PMID- 1927864 TI - 476 nm excited laser-induced fluorescence spectroscopy of human coronary arteries: applications in cardiology. AB - We have shown that normal coronary arteries and noncalcified and calcified atherosclerotic plaque can be differentiated on the basis of the 476 nm excited fluorescence spectra, providing the basis of a spectroscopic guidance system for coronary artery laser angiosurgery. This discrimination is based on extraction of parameters from tissue fluorescence spectra, which are proportional to the tissue concentrations of structural proteins (collagen and elastin) and ceroid via a model of tissue fluorescence. We use these parameters to calculate the likelihood that an area of interest in a coronary artery is normal, noncalcified, or calcified plaque. This method of diagnosing atherosclerosis provides information about the histochemical composition of atherosclerotic lesions and is thus fundamentally different from the diagnostic methods currently used. It may ultimately have bearing on a number of pertinent clinical problems. We have discussed applications to studying initiating factors in formation and progression of plaque, healing after interventional treatments, and the likelihood of restenosis after PTCA. PMID- 1927866 TI - Transient severe mitral regurgitation during percutaneous transluminal coronary angioplasty. PMID- 1927865 TI - Acute myocardial infarction due to proximal aortic dissection in giant cell aortitis. PMID- 1927867 TI - Improved myocardial perfusion following surgical correction of coronary-pulmonary connections and mitral stenosis. PMID- 1927868 TI - Amiodarone-induced hyperthyroidism: thyroidectomy under local anesthesia. PMID- 1927869 TI - Fetal and neonatal adverse effects profile of amiodarone treatment during pregnancy. PMID- 1927870 TI - AV dissociation masquerading as indeterminate supraventricular trigeminy. PMID- 1927871 TI - Facioscapulohumeral muscular dystrophy and recurrent pacemaker lead dislodgement. PMID- 1927872 TI - Isoproterenol-induced bradyarrhythmias. PMID- 1927873 TI - Evaluation of painless aortic dissection with MR imaging. PMID- 1927874 TI - Two-dimensional echocardiographic demonstration of left ventricular diastolic collapse due to compression by pleural effusion. PMID- 1927875 TI - Persistent left superior vena cava diagnosed by contrast transesophageal echocardiography. PMID- 1927876 TI - Percutaneous pulsed dye laser recanalization of experimental venous thrombosis. PMID- 1927877 TI - Doppler color flow imaging in coronary artery fistula. PMID- 1927878 TI - The clinical consequences of a stiff left atrium. PMID- 1927879 TI - The thin intima of the internal mammary artery as the possible reason for freedom from atherosclerosis and success in coronary bypass. PMID- 1927880 TI - Dynamic QRS complex and ST segment vectorcardiographic monitoring can identify vessel patency in patients with acute myocardial infarction treated with reperfusion therapy. AB - Reperfusion therapy has lowered the mortality in patients suffering acute myocardial infarction. Failure to reperfuse is associated with significantly higher risk of short- and long-term mortality. Detection of reperfusion is thus important. In a prospective pilot study, we used continuous on-line computerized vectorcardiography to monitor 21 patients with acute myocardial infarction treated with reperfusion therapy to noninvasively detect coronary patency. By using trend analysis of QRS vector difference, we were able to correctly blindly identify 15 of 16 patients with a perfused infarct-related artery and four of six patients with a persistently occluded artery at an early angiogram. The present results are based on a limited number of patients, but suggest that QRS complex and ST segment monitoring with continuous on-line vectorcardiography has substantial potential for monitoring patients with acute myocardial infarction treated with reperfusion therapy. PMID- 1927881 TI - The severity of atherosclerosis at sites of plaque rupture with occlusive thrombosis in saphenous vein coronary artery bypass grafts. AB - Atherosclerotic plaque rupture with superimposed thrombosis is recognized as the lesion causing late, acute, thrombotic saphenous vein coronary artery bypass graft (CABG) occlusion. To determine the severity of atherosclerosis at the site of plaque rupture, 68 saphenous vein CABGs removed at the time of reoperation or at autopsy were studied. The study population consisted of 57 men, 64 +/- 9 years old, and nine women, 70 +/- 10 years old. The duration of graft implantation was 7.9 +/- 2.7 years (mean +/- S.D.). All CABGs were dissected from the hearts, fixed, decalcified, cut at 2 to 3 mm intervals, and processed routinely for histologic examination. A planimeter was used to measure total vessel, plaque, thrombus, and luminal cross-sectional areas at the site of plaque rupture with thrombosis in sections projected at 13.8 power magnification. At the site of atherosclerotic plaque rupture with superimposed thrombosis, the degree of stenosis due to plaque was: 90 +/- 11% for the right coronary artery grafts (n = 19); 94 +/- 7% for the left anterior descending artery grafts (n = 41), and 90 +/ 14% for the left circumflex artery (n = 8) grafts. Thus in saphenous vein CABGs, atherosclerotic plaque rupture with thrombosis usually occurs at sites of severe narrowing (mean = 93%) by preexisting atherosclerotic plaque. PMID- 1927882 TI - Three rapid immunoassays for the determination of creatine kinase MB: an analytical, clinical, and interpretive evaluation. AB - We present analytical and clinical studies of three commercial immunoassays for the determination of the creatine kinase MB isoenzyme (CK-MB). All methods are compared with the presently-accepted reference method, agarose gel electrophoresis. We find that each of the immunoassay methods offers diagnostic sensitivity and specificity similar to those of electrophoresis, while none experiences detectable interference from high concentrations of the creatine kinase BB isoenzyme (CK-BB) or the so-called "atypical" bands. The presence of atypical bands can cause electrophoresis to yield inaccurate quantification or even misidentification of CK-MB. Because the immunoassay approaches are more rapid than electrophoresis and require less technical expertise, it is possible to evaluate patients in a more timely and cost-effective manner. Further, since immunoassay results can be available in approximately 1/2 hour, rapid real-time decisions can be made regarding the desirability of initiating or continuing such valuable but dangerous procedures as thrombolytic therapy. PMID- 1927883 TI - Prolonged bleeding time as a marker of venous clot lysis during streptokinase therapy. AB - Despite their expense and inconvenience, serial ultrasound or venographic examinations are currently the only available methods to assess the efficacy of thrombolysis for deep venous thrombosis (DVT). We therefore tested whether the bleeding time (BT), a simple and inexpensive test, is useful in assessing lytic efficacy and might thus be a valuable adjunct in guiding the dose and duration of the thrombolytic agent. Serial BTs were obtained daily in 16 patients (eight men and eight women, average age 45.5 years, range 19 to 70) receiving streptokinase (SK) for proximal lower extremity DVT (n = 5), for upper extremity DVT (n = 10), or for renal vein thrombosis (n = 1). Duration of treatment averaged 89.9 +/- 43.6 hours (range 35 to 198 hours). Clot lysis on ultrasound, venogram, or magnetic resonance imaging (MRI) was defined as: complete (greater than or equal to 90%), moderate (50% to 90%), minimal (less than 50%), or none. Important (complete or moderate) clot lysis occurred in 9 of 15 patients for whom follow-up studies were available. BT prolongation was defined as greater than 9.5 minutes and, during SK therapy, had a sensitivity of 0.67 and a specificity of 0.67 for important clot lysis. The positive predictive value of prolonged BT for clot lysis was 0.75. Calculated likelihood ratios revealed that a patient with BT prolongation was twice as likely to have important clot lysis rather than minimal or no lysis. These findings suggest that the BT should undergo further investigation as a simple, adjunctive, noninvasive marker of thrombolytic efficacy among DVT patients treated with SK. PMID- 1927884 TI - Comparison of thallium-201 SPECT and planar imaging methods for quantification of experimental myocardial infarct size. AB - To compare single photon emission computed tomography (SPECT) and planar thallium 201 (TI-201) myocardial perfusion imaging methods for quantification of left ventricular infarct size, 12 dogs with 6 to 8 hours of closed-chest coronary occlusion and 5 normal dogs were studied. After intravenous administration of TI 201, SPECT and three-view planar images were obtained. After the animals were put to death, hearts were sliced and stained with triphenyltetrazolium chloride (TTC) for planimetric determination of left ventricular infarct size. Infarct size on each SPECT slice and planar image was defined as the percentage of circumferential count profiles falling below the limits derived from normal dogs. Infarct size as a percentage of left ventricular mass was determined from SPECT and planar images before and after correcting for differences in myocardial slice mass from apex to base. The correlation coefficients, the concordance correlation coefficients (reflecting closeness to the line of identity), and the mean absolute deviations of the four methods versus TTC staining were 0.83, 0.77, and 5.1% (SPECT, no correction); 0.85, 0.84, and 3.7% (SPECT with correction); 0.81, 0.42, and 12.9% (planar, no correction); and 0.75, 0.49, and 10.4% (planar with correction). The regression lines did not differ from the line of identity for SPECT, whereas they differed significantly for planar imaging. Thus both SPECT and planar imaging are well suited for quantification of left ventricular infarct size. SPECT, however, appears to be superior to planar imaging, since its regression line more closely approximates the line of identity. PMID- 1927885 TI - The predictive value of preoperative silent ischemia for postoperative ischemic cardiac events in vascular and nonvascular surgery patients. AB - Silent ischemia has been shown to be predictive of postoperative cardiac events in vascular surgery patients. However, no controlled data regarding its predictive value in nonvascular surgery patients are available. We studied 67 vascular surgery and 79 nonvascular surgery patients, all of whom had increased risk for cardiac disease, to determine whether the occurrence of preoperative silent myocardial ischemia is predictive of morbid postoperative cardiac events in a diverse surgical group. The presence of preoperative silent ischemia in both nonvascular and vascular surgical patients had similar predictive value (0.38 and 0.38, respectively) for postoperative morbid cardiac events. The absence of preoperative silent ischemia predicted an excellent outcome in patients undergoing nonvascular surgery (0.99), but was a less robust predictor in our vascular patients (0.86). These data suggest that the functional status of the coronary circulation is one of the most important determinants of outcome. PMID- 1927886 TI - Managing cardiovascular risk and left ventricular hypertrophy. New prospects in antihypertensive therapy. Introduction. PMID- 1927887 TI - Vascular smooth muscle cell proliferation and its therapeutic modulation in hypertension. AB - The increased growth potential of vascular smooth muscle cells (VSMCs) represents one of the crucial anomalies responsible for the development of essential hypertension, diabetic macroangiopathy, and atherosclerosis. The exaggerated response to growth factors of VSMC from spontaneously hypertensive rats (SHRs) persists in culture when compared with normotensive Wistar-Kyoto control rats, indicating an intrinsic defect in the hypertension-producing mechanism. This greater proliferation is characterized by two intermediate phenotypes: (1) accelerated entry into the S phase of the cell cycle, which results from hyperresponsiveness to epidermal growth factor and platelet-derived growth factor, and (2) abnormal contact inhibition. The enhanced expression of transforming growth factor beta 1 (TGF-beta 1) messenger ribonucleic acid in SHRs precedes this altered contact inhibition, and only VSMCs from SHRs respond to exogenously added TGF-beta 1 at a high cell density, which suggests that abnormal TGF-beta 1 autoregulation may be implicated in the second phenotype. Platelets contain major growth factors for VSMC. Platelet extracts from hypertensive and diabetic patients present augmented growth-promoting activity on VSMCs, which is most evident when both diseases occur simultaneously. Growth-promoting activity may be further influenced by antihypertensive therapy. This growth-promoting activity is increased by hydrochlorothiazide but not by indapamide, atenolol, or captopril in diabetic hypertensive and nondiabetic hypertensive patients. In conclusion, VSMCs in hypertension manifest an intrinsic growth defect that is modulated by extrinsic platelet growth factors and antihypertensive drugs. PMID- 1927889 TI - Hypertension in the elderly patient. AB - Several trials have demonstrated a significant reduction in morbidity from cardiovascular disease with the treatment of diastolic hypertension in elderly persons. The pilot trial of the Systolic Hypertension in the Elderly Patient study showed a reduction in morbidity and mortality from stroke with less of a reduction in death from cardiac conditions in elderly patients who were treated. Isolated systolic hypertension in elderly persons has a particularly hazardous connection with morbidity and mortality from stroke and cardiovascular disease. The mechanisms of hypertension are different, if not greatly so, in the elderly population. Peripheral vascular resistance plays a major role. However, reduction in peripheral vascular resistance can still be demonstrated with exercise in older patients. Two major studies are ongoing--the Systolic Hypertension European trial and the Systolic Hypertension in the Elderly Patient trial. We await the outcome of these trials to learn more about the treatment of isolated systolic hypertension in elderly patients. PMID- 1927888 TI - Hyperlipidemia in hypertension: causes and prevention. AB - Hyperlipidemia is prevalent in hypertension, but the cause of this association is unknown. Treatment of hypertension with thiazide diuretics accentuates the hyperlipidemia, perhaps by causing potassium or sodium depletion. To assess the role of hypokalemia in thiazide hyperlipidemia, I measured lipid concentrations while using a spironolactone-thiazide regimen to prevent potassium wastage during the treatment of hypertension. Blood pressure decreased substantially, but hyperlipidemia occurred despite the maintenance of normal serum potassium. To test a role of sodium balance, I measured lipid levels during periods of sodium feeding and placebo therapy. Cholesterol levels decreased during sodium administration. Carrying this information to therapy, I participated in a multicenter comparison of enalapril and indapamide therapy in resistant hypertension. Both regimens caused minor metabolic effects, but indapamide provided superior antihypertensive potency. This evidence suggests that sodium feeding improves lipid metabolism, but sodium diuresis enhances an antihypertensive effect. Low-dose therapy combining a diuretic, such as indapamide, with a nondiuretic agent promises to improve metabolic tolerance and maximize hypertension control. This strategy optimally lowers overall cardiovascular risk. PMID- 1927890 TI - Glomerular capillary pressure and hypertension. AB - In patients with essential hypertension, glomerular filtration rate remains normal or elevated, whereas renal blood flow tends to be lower, which results in an increased filtration fraction. The afferent (preglomerular) arteriolar resistance determines the fraction of the pressure that is transmitted to the glomerular capillary network, whereas the efferent (postglomerular) arteriolar resistance determines the outgoing pressure. The relationship between these two resistances, renal plasma flow and the ultrafiltration coefficient will determine the glomerular capillary pressure. In hypertension the glomerular capillary pressure tends to increase because the reduction in afferent arteriolar resistance is greater than the reduction in efferent resistance. Because these resistances and the systemic pressure do not change similarly, reduction in systemic pressure may not translate necessarily or completely into a reduction of glomerular capillary pressure. The choice of antihypertensive drugs may influence the progression of any reduction in renal function based as much on their effect on the glomerular capillary pressure as on their effect on the systemic pressure. PMID- 1927891 TI - Regression of microalbuminuria in type II diabetic, hypertensive patients after long-term indapamide treatment. AB - The influence of hypertension on the progression of persistent microalbuminuria in type II diabetes has not yet been clarified. We have studied the effects of 36 months of indapamide treatment (2.5 mg once daily) on blood pressure (BP), albumin excretion rate (AER), urinary immunoglobulin G4 (IgG4), and glomerular filtration rate (GFR) in 10 patients who were mildly hypertensive and had type II microalbuminuric diabetes (AER greater than 30 mg/24 hours and less than 300 mg/24 hours). BP, AER, and IgG4 significantly decreased after 6 months until the end of the study. Mean GFR was 94.4 +/- 7.5 ml/min/1.73 m2 in the baseline and did not change significantly throughout the course of the antihypertensive therapy. AER and IgG4 were directly related (r = 0.57; p less than 0.004), whereas BP did not relate to GFR, AER, or IgG4. The nephropathy index (45.5 +/- 4 in the baseline) significantly decreased at 12 months (38.7 +/- 2.1), 24 months (35.4 +/- 1.6), and 36 months (36.5 +/- 1.5) (at least p less than 0.01). Long term indapamide treatment reduced BP and urinary protein loss without affecting GFR. These results indicate a potential role of this drug in the long-term renal protection of patients with type II diabetes, mild hypertension, and microalbuminuria. PMID- 1927892 TI - Carpal tunnel syndrome: a job-related risk. PMID- 1927893 TI - Promising news about antiarrhythmic drug therapy. PMID- 1927894 TI - Patient drug information hotlines multiply. PMID- 1927895 TI - Two panels say FDA needs better management, should be independent. PMID- 1927896 TI - On FDA's future. PMID- 1927897 TI - George B. Griffenhagen: 1991 Remington Medalist. PMID- 1927898 TI - Selecting pharmacists for the chain pharmacy. PMID- 1927899 TI - Advertising and the law: ten years later. PMID- 1927900 TI - Drug Product Selection--Part 2: Scientific basis of bioavailability and bioequivalence testing. PMID- 1927901 TI - William E. McCormick, CIH--a salute to a true professional. PMID- 1927902 TI - A simplified IAQ Questionnaire to obtain useful data for investigating sick building complaints. PMID- 1927903 TI - International Union, United Automobile, Aerospace and Agricultural Implement Workers of America, UAW, et al. vs. Johnson Controls, Inc.--Part I: Overview. PMID- 1927904 TI - Exposure variability in the workplace: its implications for the assessment of compliance. PMID- 1927905 TI - Radon gas testing: a poor indicator of radon daughter exposure. PMID- 1927906 TI - Simplified pressure method for respirator fit testing. AB - A simplified pressure method has been developed for fit testing air-purifying respirators. In this method, the air-purifying cartridges are replaced by a pressure-sensing attachment and a valve. While wearers hold their breath, a small pump extracts air from the respirator cavity until a steady-state pressure is reached in 1 to 2 sec. The flow rate through the face seal leak is a unique function of this pressure, which is determined once for all respirators, regardless of the respirator's cavity volume or deformation because of pliability. The contaminant concentration inside the respirator depends on the degree of dilution by the flow through the cartridges. The cartridge flow varies among different brands and is measured once for each brand. The ratio of cartridge to leakflow is a measure of fit. This flow ratio has been measured on human subjects and has been compared to fit factors determined on the same subjects by means of photometric and particle count tests. The aerosol tests gave higher values of fit. PMID- 1927907 TI - Permeation testing of protective gloves by using two different permeation cells in an open-loop system (neoprene-toluene). AB - Two permeation test cells of different sizes were used in a study of the permeation of toluene through two neoprene gloves and special neoprene sheet stock. Three flow rates of the collecting medium through the test cells were used to explore to what extent variation in flow rate would affect the breakthrough times and the steady-state permeation rate. The breakthrough time values were not affected to a significant degree by cell size or by increasing the flow rate of the collecting medium from 60 to 120 mL/min. The steady-state permeation rate values were evidently influenced by the flow rate of the collecting medium and by the size and configuration of the test cell. PMID- 1927909 TI - Ion chromatographic measurement of fluoride and sulfur dioxide in samples collected at aluminum smelters. AB - Measurement of airborne fluoride and sulfur dioxide in aluminum smelting plants is important for both industrial hygiene and environmental reasons. The traditional analytical techniques employed have been ion-selective electrodes (ISE) for fluoride and barium/thorin titration for SO2. In this study, ion chromatography (IC) was evaluated as a substitute for these two techniques. Dust for particulate fluoride was collected on membrane filters with carbonate-treated backup pads to collect HF and SO2. Gaseous fluoride and SO2 were ultrasonically extracted from the treated pad, but particulate fluoride required a borate/carbonate fusion. Collection efficiency and recovery of the analytes, along with the acceptable working ranges and instrument conditions used with IC, are discussed. IC is a desirable substitute for the electrode and titration methods because it is easily automated and the two determinations may be performed simultaneously. Organic compounds may cause interference in low-level fluoride measurement. Comparison of the techniques for field samples indicates that IC is an adequate substitute for the traditional measurement methods for full-shift samples of fluoride. PMID- 1927908 TI - The generation and characterization of silicon carbide whiskers (fibers) for inhalation toxicology studies. AB - Atmospheres of silicon carbide whiskers (wh) were required for a repeated dose lung deposition study and a subchronic inhalation toxicity study, each involving exposure to three concentrations of whiskers for 6 hr/day, 5 days/week for 1 or 13 weeks. Target concentrations were 0, 500, 1500, and 7500 wh/cc. By using the mean fiber length (10 microns), diameter (0.555 micron), and density (3.2 g/cc) of the bulk material, target mass concentrations were approximately 0, 4, 12, and 60 mg/m3. The Pitt III generator, developed for cotton fiber dispersion at the University of Pittsburgh, was selected. This instrument consists of a vertical 18 in. long cylinder, which is closed at each end with rubber dams and coupled at the base to a loudspeaker. The sonic energy from the loudspeaker fluidizes the test material and the whiskers in the air column are carried out with the exhaust air. The output of the Pitt III generator was altered by changing the sound energy input, the rate of introduction of the test material into the fluidizing cylinder, or the airflow through the cylinder. Separate generation systems were used for each inhalation chamber. Chamber atmospheres were characterized gravimetrically and samples were analyzed by scanning electron microscopy. Mean mass and number concentrations for the subchronic study were 0.09, 3.93, 10.7, and 60.5 mg/m3 and 0, 630, 1746, and 7276 wh/cc, respectively. Weighted mean values for whisker diameters, lengths, and aspect ratios were 0.560 micron, 4.53 microns, and 8.62, respectively. Although whisker lengths were less than half those of the bulk material, nearly 30% of the whiskers were greater than 5 microns long. PMID- 1927910 TI - Hazard assessment of video display units. AB - This report describes the results of a study of potential health hazards of video display units (VDUs). The specific elements of the study included characterizing the emissions of ionizing and nonionizing radiation and exposures to electromagnetic fields. There was no evidence that operators are exposed to electric, magnetic, or ionizing radiation fields significantly above ambient levels. Significant x-ray leakage cannot occur under any credible conditions. In addition to the ergonomic aspects of VDU work, reports on the health aspects of VDU operators were investigated. The results of the study, based on the specific hazards evaluated, do not support allegations that VDU operation is hazardous beyond the identified transient discomforts associated with characteristics of the work performed. A high-profile employee education program was initiated to minimize discomforts and unwarranted concerns. PMID- 1927911 TI - Usefulness of oral nisoldipine for stable angina pectoris. The Nisoldipine Multicenter Angina Study Group. AB - The duration and extent of antianginal effects of nisoldipine, a dihydropyridine calcium antagonist, were assessed in 178 patients with chronic stable angina pectoris. Using a placebo run-in, placebo-controlled, randomized, parallel study design, patients received placebo twice daily for 2 to 3 weeks and were then randomized to receive either placebo (n = 42), nisoldipine 10 mg once daily (n = 44), nisoldipine 10 mg twice daily (n = 47) or nisoldipine 20 mg once daily (n = 45) for 5 weeks. Frequency of angina and nitroglycerin consumption were assessed by weekly patient diaries. Exercise tolerance time was assessed at baseline and at weeks 1, 3 and 5 in the double-blind phase. Peak effects after 5 weeks of double-blind medication showed significant or nearly significant improvements with nisoldipine over placebo in time-to-termination of exercise, time to onset of angina, and time to onset of 1 mm ST-segment depression. There were no significant improvements in trough effects with nisoldipine. Also, placebo was not significantly different from nisoldipine in either the number of anginal attacks or nitroglycerin consumed. Although significantly more drug-related, adverse effects were observed with the nisoldipine regimen, 20 mg once daily, compared with placebo, nisoldipine appears to be an effective and well-tolerated antianginal drug. However, its duration of antianginal action, as measured by exercise stress testing, is relatively short. The drug needs to be examined using shorter dosing intervals and higher daily doses, or in a longer-acting sustained release formulation. PMID- 1927912 TI - Alcohol intake and nonfatal acute myocardial infarction in Japan. AB - The relation between alcohol and nonfatal acute myocardial infarction (AMI) was examined in a case-control study of 89 male patients and 271 control subjects in Fukuoka, Japan. Patients admitted for the first AMI at 2 hospitals in Fukuoka City were aged 40 to 69 years, and control subjects were recruited based on the telephone directory of the city. Information on alcohol drinking and potential coronary risk factors was obtained by using a self-administered questionnaire, and past drinkers were separated from lifelong abstainers in the analysis. After adjustment for age, occupation, cigarette smoking, strenuous exercise, body mass index, hypertension, diabetes mellitus and parental heart disease, the risk of AMI was progressively less with increasing levels of alcohol consumption. With those who never drank as a referent, adjusted odds ratios for current drinkers consuming less than 30, 30 to 59, and greater than or equal to 60 ml/day of alcohol were 1.11 (95% confidence interval 0.51 to 2.42), 0.31 (0.11 to 0.83), and 0.13 (0.05 to 0.36), respectively. These findings add to the body of data showing that alcohol drinkers are less likely to have AMI. PMID- 1927913 TI - Thrombolytic therapy in patients requiring cardiopulmonary resuscitation. AB - Cardiopulmonary resuscitation (CPR) is often considered a contraindication to thrombolytic therapy for acute myocardial infarction. Of 708 patients involved in the first 3 Thrombolysis and Angioplasty in Myocardial Infarction trials of lytic therapy for acute infarction, 59 patients required less than 10 minutes of CPR before receiving lytic therapy (CPR greater than 10 minutes was an exclusion of the trials) or required CPR within 6 hours of treatment. The patients receiving CPR were similar to the remainder of the group with respect to baseline demographics. The indication for CPR was usually ventricular fibrillation (73%) or ventricular tachycardia (24%). The median duration of CPR was 1 minute, with twenty-fifth and seventy-fifth percentiles of 1 and 5 minutes, respectively. The median number of cardioversions/defibrillations performed was 2 (twenty-fifth and seventy-fifth percentiles of 1 and 3 minutes, respectively). Patients receiving CPR were more likely to have anterior infarctions (66 vs 39%), the left anterior descending artery as the infarct-related artery (63 vs 38%) and lower ejection fractions on the initial ventriculogram (46 +/- 11 vs 52 +/- 12%) than those not receiving CPR. In-hospital mortality was 12 vs 6% with most deaths due to pump failure (57%) or arrhythmia (29%) in the CPR group and pump failure (38%) or reinfarction (25%) in the non-CPR group. At 7 day follow-up the CPR group had a significant increase in ejection fraction (+5 +/- 9%) compared with no change in non-CPR group. There were no bleeding complications directly attributed to CPR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927914 TI - Risk of thrombosis during coronary angioplasty with low osmolality contrast media. AB - Studies in vitro have suggested that nonionic low osmolar contrast agents produce an increase in thrombogenicity. To determine the incidence of thrombi related to the use of nonionic low osmolar contrast media during coronary angioplasty, a double-blind randomized study was performed in 100 patients. Medication before angioplasty included oral aspirin (250 mg/day) in all cases. At the beginning of the procedure, aspirin (250 mg) and heparin (10,000 U) were intravenously administered. During the procedure patients were randomly assigned to receive either an ionic low osmolar contrast agent ioxaglate (n = 50), or a nonionic low osmolar contrast media iohexol (n = 50). The presence of thrombus was evaluated on the angiogram and on the guidewire immediately after its retrieval from the patients. Clinical, angiographic and procedural variables were similar in the 2 randomized groups. Angiographic evidence of thrombus was observed in 1 patient (2%) assigned to ioxaglate and in 11 patients (22%) assigned to iohexol (p less than 0.005). One patient (2%) from the ioxaglate group and 6 patients (12%) from the iohexol group showed thrombotic residues on the guidewire (p = not significant). Three patients had acute myocardial infarction, 1 patient (2%) receiving ioxaglate and 2 patients (4%) iohexol (p = not significant). There were no deaths. Thus, compared with an ionic low osmolar contrast media ioxaglate, the nonionic low osmolar contrast agent iohexol increases the incidence of thrombus during coronary angioplasty. PMID- 1927915 TI - An antiarrhythmic drug experience in 941 patients resuscitated from an initial cardiac arrest between 1970 and 1985. AB - Survival rates and antiarrhythmic drug use were determined in 941 consecutive patients resuscitated from prehospital cardiac arrest due to ventricular fibrillation between March 7, 1970, and March 6, 1985. Of these patients, 18.7% were treated for at least a portion of the period with quinidine, 17.5% with procainamide, and 39.4% received no antiarrhythmic agent. Beta blockers were prescribed for 28.3% of the patients. Unadjusted comparisons of survival estimates showed dramatically lower survival rates for patients who received antiarrhythmic drugs independent of beta-blocker therapy and significantly improved survival for patients receiving beta-blocker therapy independent of antiarrhythmic use. Patients for whom antiarrhythmic therapy was prescribed also had more adverse baseline risk factors, whereas patients taking beta blockers had fewer such risk factors. After adjustment for these baseline risk factors, the use of antiarrhythmics was weakly (p less than 0.09) associated with worsened survival; 2-year survival for procainamide-treated patients was 30% and quinidine treated patients 55% (p = 0.003). Beta-blocker therapy was associated with improved (p less than 0.001) survival. Thus, although neither procainamide nor quinidine appear to have had a benefit on mortality, the effect of procainamide appears to be significantly worse than that of quinidine. The use of antiarrhythmic drug therapy in patients resuscitated from prehospital ventricular fibrillation should be regarded as not only unproved, but potentially hazardous, and should probably be restricted to testing in randomized clinical trials. PMID- 1927916 TI - Neurally mediated syncope detected by carotid sinus massage and head-up tilt test in sick sinus syndrome. AB - It is generally accepted that a positive response to carotid sinus massage (CSM) or head-up tilt (HUT) in patients affected by syncope suggests a reflex cause of the syncope. To study the role of the autonomic nervous system in causing syncope in the sick sinus syndrome (SSS), CSM and HUT were performed in 35 consecutive patients (20 men, mean age 70 +/- 9 years) with syncope and SSS. Results were compared with those in 35 patients affected by syncope that, despite careful cardiovascular and neurologic examination, were of uncertain origin (21 men; mean age 68 +/- 9 years) and with those of 35 subjects without syncope (20 men; mean age 69 +/- 10). All patients underwent CSM in the supine and standing positions for 10 seconds and HUT to 60 degrees for 60 minutes. In the patients with SSS, the full reproduction of spontaneous symptoms by CSM occurred in 21 (60%) and by HUT, in 19 (54%). At least 1 test was positive in 28 patients (80%): cardioinhibitory or mixed responses in 69%, vasodepressor responses in 11%. The percentages of positive tests in the patients with syncope of uncertain origin were similar to or slightly less than those of patients with SSS (CSM 63%, HUT 26%, overall 74%) with cardioinhibitory or mixed responses in 54% and vasodepressor in 20% (p less than 0.05). In control subjects, syncope was induced by CSM in 1 (3%) and by HUT in 2 (6%); overall positivity was 9%. In conclusion, in most patients affected by syncope and SSS, an abnormal neural reflex probably plays a major role in causing syncope.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927917 TI - Usefulness of the delta HA interval to accurately distinguish atrioventricular nodal reentry from orthodromic septal bypass tract tachycardias. AB - Surface electrocardiographic criteria may be inadequate to distinguish some cases of atrioventricular (AV) nodal reentrant supraventricular tachycardia (SVT) from those with orthodromic SVT incorporating a posterior septal bypass tract (orthodromic SVT) because of similarities in P-wave morphology and timing during SVT. Invasive electrophysiologic studies may occasionally leave uncertainty in the correct diagnosis, using currently accepted criteria. A new criterion for distinguishing these 2 forms of SVT was therefore devised and tested based on differences in the sequence of activation of the His bundle and atrium during SVT and ventricular pacing. Eighty-four patients underwent invasive electrophysiologic studies (60 with proved AV nodal SVT, 24 with proved orthodromic SVT), during which His to atrial (HA) intervals were measured during SVT as well as ventricular pacing at the same rate. The newly devised criterion, the delta HA interval (HApace-HAsvt) was found to accurately distinguish AV nodal SVT (delta HA greater than 0 ms) from orthodromic SVT (delta HA less than -27 ms). An intermediate value of delta HA = -10 ms was chosen which had a 100% sensitivity, specificity and predictive accuracy in differentiating the 2 forms of SVT. A clear retrograde His potential during ventricular pacing, which is essential for application of this criterion, was present in 78 of 84 (93%) cases. In summary, patients with delta HA intervals greater than -10 ms separate AV nodal reentry from orthodromic SVT incorporating a septal bypass tract, and no overlap exists between the 2 groups. This criterion may be useful in differentiating the mechanism of SVT in cases in which distinction is not possible by other methods. PMID- 1927918 TI - Left atrial afterload mismatch in hypertrophic cardiomyopathy. AB - To investigate left atrial (LA) booster pump function in hypertrophic cardiomyopathy (HC), LA and left ventricular pressure-volume loops were estimated in 5 control subjects, 6 patients with essential hypertension and 11 patients with HC. Investigation of LA preload revealed that LA pressure and volume immediately before LA contraction were both increased in patients with hypertension (10 +/- 5 mm Hg, 71 +/- 19 ml/m2) compared with control subjects (7 +/- 1 mm Hg, 59 +/- 6 ml/m2), and even more increased in patients with HC (16 +/- 7 mm Hg, 81 +/- 25 ml/m2). Investigation of LA afterload revealed that the left ventricular chamber stiffness constant was higher in patients with hypertension (0.035 +/- 0.015) than in control subjects (0.028 +/- 0.009), and even more increased in patients with HC (0.056 +/- 0.017). LA stroke work index was higher in patients with hypertension (116 +/- 34 mm Hg.ml) and HC (115 +/- 19 mm Hg.ml) than in control subjects (87 +/- 23 mm Hg.ml). Investigation of LA ejection revealed that LA stroke index was higher in patients with hypertension (24 +/- 5 ml/m2) than in control subjects (18 +/- 4 ml/m2) and patients with HC (18 +/- 2 ml/m2), and LA ejection fraction was lower in patients with HC (23 +/- 6%) than in control subjects (32 +/- 7%) and patients with hypertension (34 +/- 8%). In patients with HC, LA function curve showed a shift to the lower right, and LA stroke index was inversely correlated (r = -0.76) with LA afterload. This study suggests that LA booster pump failure due to LA afterload mismatch exists in HC. PMID- 1927919 TI - Determinants of outcome in hospitalized infants with congenital heart disease. AB - To identify determinants of adverse outcome in this era of early, definitive treatment, retrospective data were analyzed for 1988 on infants aged less than 1 year with congenital cardiac disease hospitalized at The Johns Hopkins Hospital. In this cohort of 108 infants, 34% (37 of 108) had complex cardiac disease, 33% (36 of 108) had major extracardiac anomalies, 88 patients (81%) underwent 116 surgical procedures, 37% (40 of 108) were hospitalized for greater than 28 days and 29% (31 of 108) died during the first year. Univariate analysis showed that complex disease (i.e., severe ventricular hypoplasia, ventricular septal malalignment or outflow atresia), extracardiac anomalies, early initial presentation, and prolonged stay in the intensive care unit were significantly associated with infant death, whereas surgery was associated with a significantly increased rate of survival. The findings for complex disease and surgery persisted in multiple logistic regression analysis. It is concluded that outcome in most infants with congenital cardiac defects is now extremely favorable, and that major research and preventive efforts should focus on complex congenital cardiac defects. PMID- 1927922 TI - Determination of left atrial area and volume by cross-sectional echocardiography in healthy infants and children. AB - Part 1 of the study measured the end-systolic and end-diastolic left atrial (LA) areas and volumes in 30 children through sector echocardiography, and compared these values with those obtained with biplane angiocardiography. A strong correlation exists between the LA area in the frontal plane as determined by apical (r greater than 0.91) and subcostal (r greater than 0.98) echocardiography on the one hand and by angiocardiography on the other. However, there is a slight underestimation of the LA area by the apical 4-chamber view. LA volume as determined by subcostal sector echocardiography in the frontal and sagittal plane also correlated well with LA volume calculated with biplane angiocardiography (r greater than 0.97). Part 2 of the study determined LA areas and volumes in 74 healthy newborns and infants by echocardiography and related them to body weight and body surface area, thus obtaining normal values for this age group. The relation of the LA area and volume measurements in newborns and infants to body weight or surface area was best described by a linear function. The mean of the percentage of systolic-diastolic area diminution was 53 +/- 6% for the apical 4 chamber view and 50 +/- 4% for the subcostal 4-chamber view. LA ejection fraction determined by the subcostal biplane volume measurements was 62 +/- 7% (mean +/- standard deviation). These values were independent of body weight or surface area. PMID- 1927921 TI - Combined ambulatory electroencephalographic and electrocardiographic recordings for evaluation of syncope. AB - Evaluation of patients with syncope often includes a battery of noninvasive tests. In this study, 45 patients (26 with suspected neurologic and 19 with suspected cardiac syncope) were evaluated with simultaneous 24-hour electroencephalographic (EEG) and 2-channel electrocardiographic (ECG) recordings. Isolated cardiac rhythm abnormalities were noted in 21 patients, but none of these was symptomatic and no definitive arrhythmias occurred. Isolated EEG abnormalities were noted in 11 patients, 5 of whom had EEG abnormalities consistent with seizure disorders. Simultaneous EEG and ECG abnormalities were seen in 4 patients. In 2 cases, a previously unsuspected etiology for syncope was found: seizures in 1 patient with heart disease, and sinus pauses in another thought to have a seizure disorder. Thus, combined ambulatory EEG/ECG monitoring may prove useful in the evaluation of some patients with syncope. PMID- 1927923 TI - National Cholesterol Education Program's recommendations, and implications of "missing" high-density lipoprotein cholesterol in cardiac rehabilitation programs. PMID- 1927920 TI - Improvement in exercise capacity after correction of anemia in patients with end stage renal failure. AB - Changes in exercise tolerance occurring after correction of anemia with recombinant human erythropoietin in a group of patients with end-stage renal failure were evaluated. Ten patients, aged 29 +/- 11 years, on chronic hemodialysis treatment, with no associated diseases, were evaluated by cardiopulmonary bicycle exercise testing and M-mode, 2-dimensional and pulsed doppler echocardiography before and after anemia correction. After 1 and 3 months of therapy, hemoglobin plasma levels increased from 5.9 +/- 1.2 to 7.7 +/- 1.3 and 9.9 +/- 1.4 g/dl, with a concomitant increase in peak oxygen consumption (VO2) from 21.4 +/- 4.3 to 24.4 +/- 4.3 and 26.6 +/- 4.6 ml/kg/min and of VO2 at the ventilatory threshold from 15.0 +/- 3.7 to 17.3 +/- 3.7 and 16.8 +/- 3.4 ml/kg/min. After 3 months of therapy, systolic blood pressure significantly decreased both at peak exercise (159 +/- 35 to 134 +/- 22 mm Hg) and ventilatory threshold (140 +/- 27 to 123 +/- 19 mm Hg), whereas cardiac index at rest decreased from 3.3 +/- 0.7 to 2.8 +/- 0.5 liters/min/m2 and heart rate from 77 +/ 12 to 70 +/- 10 beats/min. However, no significant relation was found between hemoglobin plasma levels and peak VO2, whereas a significant relation was found between hemoglobin concentration and cardiac index at rest. PMID- 1927924 TI - Usefulness of magnetic resonance imaging for diagnosis of acute myocarditis in infants and children, and comparison with endomyocardial biopsy. PMID- 1927926 TI - Noncapturing stimuli during the basic drive shorten ventricular refractoriness. PMID- 1927925 TI - Incidence of QT interval prolongation during pentamidine therapy of Pneumocystis carinii pneumonia. PMID- 1927927 TI - Role of dipyridamole thallium-201 imaging in left bundle branch block. PMID- 1927928 TI - Unexpected ventricular tachyarrhythmias soon after cardiac surgery. PMID- 1927929 TI - Effects of beta blockade on the relation between heart rate and ventricular diastolic perfusion time during exercise in systemic hypertension. PMID- 1927930 TI - Usefulness of hydralazine to withdraw from dobutamine in severe congestive heart failure. PMID- 1927931 TI - Assessment of the mitral valve splitability score by transthoracic and transesophageal echocardiography. PMID- 1927932 TI - Clinical and anatomic observations in patients having mitral valve replacement for pure mitral regurgitation and simultaneous tricuspid valve replacement. PMID- 1927933 TI - Effectiveness of percutaneous balloon valvuloplasty in adults with pulmonic valve stenosis. PMID- 1927934 TI - Plasma endothelin-1 levels in idiopathic dilated cardiomyopathy. PMID- 1927935 TI - Frequency of respiratory compromise after ketamine sedation for cardiac catheterization in patients less than 21 years of age. PMID- 1927936 TI - Comparison of cardiovascular and renal toxicity after cardiac catheterization using a nonionic versus ionic radiographic contrast agent. PMID- 1927937 TI - Economic evaluation of cholesterol lowering. PMID- 1927938 TI - Enhanced effectiveness of combined sustained-release forms of isosorbide dinitrate and diltiazem for stable angina pectoris. AB - In 14 patients with documented coronary artery disease, the extent and duration of acute anti-ischemic, antianginal and hemodynamic effects of monotherapies with 120 mg of sustained-release isosorbide dinitrate and diltiazem were compared; their combined therapy administered once daily in the morning with diltiazem given again in the evening were also compared according to a randomized, double blind, crossover, placebo-controlled protocol including exercise testing for assessment of ST-segment depression (ST decreases) at an identical work load, exercise capacity and determination of plasma concentrations of both substances. Comparison of individual substances revealed more marked and sustained effects of isosorbide dinitrate (ST decreases at 2 hours, -66%; at 6 hours, -50%; p less than or equal to 0.05 for both), remaining statistically significant up to 12 hours (-24%) than of diltiazem (2 hours, -30%; 6 hours, -16%; p less than 0.05). Combined therapy resulted in increased effects (ST decreases at 2 hours, -80%; 6 hours, -76%; 12 hours, -30%; p less than or equal to 0.05) as opposed to individual substances for a period of up to 12 hours. However, therapeutic coverage over 24 hours could not be demonstrated, even with renewed administration of sustained-release diltiazem in the evening. Plasma concentrations of isosorbide-5-mononitrate were greater than 250 ng/ml for 12 hours on days when isosorbide dinitrate was given, decreasing to less than 100 ng/ml at 24 hours. On days when diltiazem was given, plasma levels greater than 50 ng/ml were detected only at 2 and at 6 hours, and at 24 hours only after a second tablet was given. PMID- 1927939 TI - Increased plasma level of endothelin-1-like immunoreactivity during coronary spasm in patients with coronary spastic angina. AB - To examine the role of endothelin in coronary spasm, the plasma endothelin-1-like immunoreactivity in the coronary sinus and the aortic root was measured before and during spasm of the left coronary artery induced by injection of acetylcholine (20 to 100 micrograms) into the left coronary artery in 26 patients with coronary spastic angina. The plasma level of endothelin-1-like immunoreactivity was measured by the radioimmunoassay with a monoclonal antibody against endothelin-1. Plasma lactate levels in the coronary sinus and the aortic root were also measured to evaluate myocardial lactate metabolism during spasm. In 13 patients who had myocardial lactate production during spasm, the plasma level of endothelin-1-like immunoreactivity in the coronary sinus increased from 19.8 +/- 3.0 to 25.7 +/- 6.4 pg/ml (p less than 0.01), while that in the aortic root remained unchanged (from 20.2 +/- 5.9 to 21.3 +/- 5.8 pg/ml). No significant changes in the plasma levels of endothelin-1-like immunoreactivity in the coronary sinus (from 21.1 +/- 7.3 to 19.7 +/- 5.2 pg/ml) and the aortic root (from 21.1 +/- 5.7 to 19.7 +/- 5.6 pg/ml) were observed in 13 patients who did not show myocardial lactate production during spasm. On the other hand, 16 patients without ischemic heart disease showed no significant changes in the plasma levels of endothelin-1-like immunoreactivity in the coronary sinus (from 24.4 +/- 9.7 to 25.8 +/- 6.9 pg/ml) and the aortic root (from 23.0 +/- 7.1 to 23.4 +/- 5.8 pg/ml) by acetylcholine injection (100 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927940 TI - Evidence of endothelial dysfunction in coronary resistance vessels in patients with angina pectoris and normal coronary angiograms. AB - This study determines whether an impaired endothelium-mediated vasodilation in coronary resistance vessels exists in patients with microvascular angina. In 23 patients with clinically suspected coronary artery disease and smooth coronary arteries in the angiogram, coronary flow in response to an endothelium-related (acetylcholine) and endothelium-unrelated (dipyridamole) vasodilation was measured. Coronary flow was determined by the gas-chromatographic argon method (1) before, (2) with intracoronary acetylcholine infusion, and (3) after dipyridamole administered intravenously. In 8 patients, acetylcholine did not significantly increase coronary flow (from 91 +/- 28 to 118 +/- 37 ml/min.100 g), whereas flow was greatly increased after administration of dipyridamole (258 +/- 97 ml/min.100 g), indicating an endothelium-related vasodilator defect. In 6 patients, neither acetylcholine nor dipyridamole caused a significant increase in coronary flow, indicating an impaired coronary vasodilation on the vascular site. In 6 patients, coronary flow increased markedly after both administration of both acetylcholine and dipyridamole (from 81 +/- 26 to 191 +/- 68 and 234 +/- 87 ml/min.100 g). In 3 patients given acetylcholine, coronary artery constriction occurred. No significant correlation was found between the response to acetylcholine and that to dipyridamole (r = 0.40, p = not significant). The results indicate that in a subgroup of patients with smooth coronary arteries angina can be caused by an abnormality of the endothelial function in the microcirculation. PMID- 1927941 TI - Comparison of risk and patterns of practice in patients older and younger than 70 years with acute myocardial infarction in a two-year period (1987-1989) AB - To further evaluate contemporary risk and practice patterns in acute myocardial infarction (AMI), 402 consecutive patients with AMI between July 1, 1988, and June 30, 1989 were studied. The clinical investigations, medical therapy and outcome of patients aged greater than or equal to 70 years (n = 132; group 1) were compared with patients aged less than 70 years (n = 270; group 2). In group 1, 20% of patients had no typical cardiac pain versus 6% in group 2 (p less than 0.01). History of previous AMI, Q-wave AMI and peak creatine kinase were not different in the 2 groups. In-hospital mortality was markedly higher in group 1 (27%) than in group 2 (8%), p less than 0.01. Multivariate analysis revealed previous AMI, presentation without typical pain and age greater than or equal to 70 years to be independently associated with the greatest relative risk. Post-AMI exercise testing, ejection fraction calculations and coronary angiography were all performed less often (p less than 0.01); proven effective medical therapies, including thrombolysis, beta blockers, acetylsalicylic acid and nitrates were all used less frequently (p less than 0.01). The very high mortality and less aggressive management of elderly patients with AMI confirm similar data from our 1987 AMI patient cohort and other recently reported AMI patient outcome analyses. However, it remains uncertain why older patients with AMI are investigated and treated differently from younger patients. Further studies are warranted. PMID- 1927942 TI - Effects of early thrombolytic therapy (anistreplase versus streptokinase) on enzymatic and electrocardiographic infarct size in acute myocardial infarction. TEAM-2 Investigators. AB - The effects of thrombolytic therapy on enzymatic and electrocardiographic indexes of myocardial infarction were examined in 370 patients who were enrolled within 4 hours of onset of symptoms and were randomized to blinded therapy with intravenous anistreplase (30 U/5 min, n = 188) or streptokinase (1.5 million IU/1 hour, n = 182). Creatine kinase and its MB isoenzyme were initially measured every 4 to 6 hours, and lactic dehydrogenase (LDH) and its cardiac isoenzyme (LDH 1) every 8 to 12 hours. Electrocardiograms were obtained before, and at 90 minutes and 8 hours after starting thrombolysis, and on discharge. Enzymatic and electrocardiographic measures of infarction were compared between drug treatment and patency groups. Early patency was associated with significant reductions in peak values for each of 4 cardiac enzymes (averaging 21 to 25%, p less than 0.01 to 0.001), even though later rescue procedures were often used in the nonpatient group; times to peaks were also reduced for 3 of the enzymes. Treatment with anistreplase was associated with enzymatic peaks that tended to be lower than with streptokinase (6 to 16%), approaching or reaching significance for LDH (p less than or equal to 0.07) and LDH-1 (p less than or equal to 0.04); times to peaks were similar. Early patency favorably affected electrocardiographic indexes. Summed ST-segment elevations resolved more rapidly (p less than or equal to 0.04), summed Q-wave amplitude was reduced by 32% (p less than or equal to 0.01), and total QRS infarct score on discharge was 22% less (p less than or equal to 0.006) in those achieving early patency. Small differences in electrocardiographic indexes between the 2 drug treatment groups were not significant. These results support use of early reperfusion to reduce infarct size in acute myocardial infarction with administration of streptokinase and anistreplase. PMID- 1927943 TI - Long-term efficacy of continuous and intermittent use of transdermal nitroglycerin in stable angina pectoris. AB - To assess efficacy of transdermal nitrate use, a randomized, placebo-controlled trial of continuous and intermittent use of nitroglycerin patches (10 mg/24 hours) was conducted in 127 patients with stable angina pectoris who discontinued exercise testing within 9 minutes because of angina. After a placebo run-in week, baseline (day 0) symptom-limited exercise testing was performed and repeated on day 1 and 14 before and after the administration of 0.5 mg of sublingual nitroglycerin. On day 0, total exercise duration was the same (within narrow limits) in all 3 groups and remained unchanged in the placebo group. On day 1, total exercise duration increased from 406 +/- 115 to 469 +/- 158 seconds (p less than 0.001) in the continuously treated group and from 396 +/- 105 to 475 +/- 171 seconds (p less than 0.001) in the intermittently treated group. In the intermittent group, exercise duration increased slightly to 483 +/- 140 seconds on day 14, and in the continuous group exercise duration decreased to 447 +/- 144 seconds. However, this decrease was not statistically significant. Similar treatment effects were seen for time to 1-mm ST depression. Sublingual nitroglycerin remained effective in all 3 groups and on all days. Eleven actively treated patients and 1 patient taking placebo discontinued the study because of headache. It is concluded that continuous use of transdermal nitroglycerin remains partially effective and intermittent therapy remains fully effective in improving long-term exercise capacity with acceptable adverse effects in patients with stable angina pectoris. PMID- 1927944 TI - Effectiveness of probucol in reducing plasma low-density lipoprotein cholesterol oxidation in hypercholesterolemia. AB - Oxidized low-density lipoprotein (LDL) interacts with macrophages to induce intracellular cholesterol ester accumulation and foam cell formation. Probucol is a lipid-lowering drug with a well-known antioxidant action. The thiobarbituric acid (TBA)-reacting substances were measured as an index of plasma and LDL lipid peroxidation in a group of hypercholesterolemic patients compared with a normolipidemic control group. The effect of probucol treatment on plasma and LDL lipid peroxidation in the hypercholesterolemic group was also evaluated. Twenty five patients (10 men and 15 women) with total cholesterol levels greater than 6.5 mmol/liter were given probucol for 24 weeks. Lipid and apoprotein measurements were obtained at 0, 12 and 24 weeks. TBA-reacting substances were also measured in plasma and the LDL fraction. Twenty-five normolipidemic subjects matched for sex, age and body mass index underwent complete blood analysis for purposes of comparison at week 0. Plasma, LDL and high-density lipoprotein cholesterol, and plasma apoproteins A-I and B significantly decreased after 12 and 24 weeks of probucol treatment. Hypercholesterolemic subjects (men and women) had significantly higher TBA-reacting substances in plasma and LDL than control subjects had (p less than 0.05). The amount of TBA-reacting substances in plasma and LDL showed a very significant decrease after probucol treatment (40 and 44%, respectively, after 24 weeks; p less than 0.05). This reduction was not related to age, sex or body mass index, and was greater than the decrease in lipids. These results support a potential role for probucol as a coadjuvant drug in any lipid-lowering antiatherogenic therapy. PMID- 1927945 TI - Evaluation of transient mitral regurgitation in coronary artery disease. AB - The pathoanatomy and factors associated with transient mitral regurgitation (MR) induced by myocardial ischemic stress are unknown. Changes in valvular and ventricular parameters during transient, stress-induced MR in patients with coronary artery disease were investigated, and the clinical characteristics of these patients were identified. Color flow Doppler echocardiography was used to quantify the MR color area, the coaptation point of the mitral leaflets, the mitral valve anulus diameter, and left ventricular volumes and wall motion in 42 patients before and immediately after exercise echocardiography (group 1, n = 27), or before and during percutaneous transluminal coronary angioplasty (PTCA) (group 2, n = 15). Of the 27 patients with exercise echocardiography, 4 developed new, transient MR (group 1B) and 9 had MR both at rest and during exercise (group 1C). Of the 15 patients with PTCA, 7 developed new MR (group 2B). New MR (groups 1B and 2B) was associated with more severe stress-induced ventricular dyskinesia (p less than 0.05) than was seen in patients with chronic MR (group 1C) or in patients without MR, and occurred predominantly in patients with left anterior descending or right coronary artery stenoses. Stress-induced MR was not associated with changes in blood pressure or in mitral valve anulus diameter, nor with the development of mitral valve prolapse. It was associated with apical displacement of the mitral leaflets in patients in group 1B and C (p less than 0.05). New MR flow areas were significantly smaller than those in patients with chronic MR (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927946 TI - Effects of low-dose aspirin on restenosis after coronary angioplasty. AB - After angioplasty of a previously untreated native coronary artery and after 2 weeks of aspirin therapy, 216 subjects (aged less than 70 years without acute infarction) were randomized to treatment with soluble aspirin, 100 mg/day, or placebo to study the effect on restenosis. Follow-up, defined as angiography at 6 months, earlier angiographic restenosis or coronary bypass surgery was completed by 108 aspirin- and 104 placebo-treated patients. Restenosis (stenosis greater than or equal to 50% plus loss of greater than or equal to 50% of gain, or surgery) occurred in 38 (35%) aspirin- and 45 (43%) placebo-treated subjects (p = not significant). No patient died. Restenosis occurred in 42 of 168 (25%) aspirin and 51 of 135 (38%) placebo-treated lesions (p less than 0.025). Aspirin-treated lesions (n = 163) had lost 16 +/- 22% (mean +/- standard deviation) of lumen and placebo-treated lesions 22 +/- 25% of lumen (n = 134) at angiography (p less than 0.01). There were more left anterior descending lesions in the placebo group and these had a higher recurrence rate than other lesions. The beneficial effect of aspirin was not dependent on this, although significance was reduced in subgroup analysis. Loss of lumen in left anterior descending lesions was 20 +/- 24% (n = 57) in the aspirin-treated and 27 +/- 25% (n = 70) in the placebo-treated lesions (p less than 0.1). It is concluded that there is a small beneficial effect of low dose aspirin on restenosis after coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927947 TI - In-hospital costs associated with new percutaneous coronary devices. AB - To determine the relative economic impact of alternative methods of coronary revascularization, in-hospital patient accounts were reviewed in 149 patients undergoing elective coronary angioplasty (n = 50), coronary atherectomy (n = 72) or intracoronary stent placement (n = 27) over an 18-month period. Clinical and angiographic features were similar in the 3 groups, except that prior restenosis was seen more often in patients undergoing intracoronary stent placement. Procedural success, obtained in greater than 90% of patients, was independent of the treatment strategy. Total in-hospital stay was significantly longer in patients undergoing intracoronary stent placement than in patients undergoing coronary angioplasty and directional atherectomy (4.9 +/- 2.4 days vs 1.5 +/- 1.3 and 2.2 +/- 3.9 days, respectively; p less than 0.0001). Furthermore, the total in-hospital charges were significantly higher in patients undergoing intracoronary stent placement ($12,574 +/- $4,564 vs $6,220 +/- $5,716; p less than 0.001) and directional atherectomy ($8,329 +/- $8,588 vs $6,220 +/- $5,716; p less than 0.01) than in patients undergoing coronary angioplasty, reflecting overall differences in room costs, laboratory fees and pharmacy fees. The longer in-hospital stay in the intracoronary stent group was primarily attributed to the time required for anticoagulation with coumadin. It is concluded that a 102 and 34% increase in early hospital charges resulted with stenting or directional atherectomy, respectively, compared with coronary angioplasty. These increased in hospital charges were chiefly due to the prolonged hospitalization time, device cost, laboratory fees and, in patients with intracoronary stents, the prolonged time needed to achieve systemic anticoagulation. PMID- 1927949 TI - Periodicity of global ventricular activation of sinus beats in patients with coronary artery disease and sustained ventricular tachycardia. AB - Despite increasing clinical reliance on signal-averaged electrocardiograms for determining risk for development of sustained ventricular tachycardia (VT), the periodicity of global ventricular activation during sinus rhythm has not been defined. Accordingly, epicardial and transmural ventricular electrograms during 6 consecutive sinus beats were evaluated in 10 patients with abnormal signal averaged electrocardiograms who were undergoing surgery for VT. Bipolar electrograms were recorded with sock and needle electrodes from up to 96 epicardial and 156 transmural sites. Electrogram morphology, duration and activation were compared on a beat-to-beat basis. In all, 9,816 electrograms were analyzed. Mean durations of epicardial and transmural electrograms were 33 +/- 16 ms (range 6 to 199) and 23 +/- 10 ms (range 6 to 72), respectively, with a beat to-beat variation of 1.9 +/- 1.4 ms per site. Similarly, local activation times did not vary significantly during the 6 cardiac cycles analyzed (mean variation 1.7 +/- 2.0 ms). Local conduction failure was not observed. Although electrograms during the terminal 40 ms of the QRS were significantly longer (36 +/- 20 vs 26 +/- 12 ms, p less than 0.001) when compared with those recorded earlier during the QRS complex, beat-to-beat variation in duration (2.1 +/- 1.6 ms) and activation (1.7 +/- 2.3 ms) was not significant. Results demonstrate that epicardial and transmural electrograms recorded during sinus rhythm in patients with sustained VT are periodic signals and thus establish a physiologic basis for signal averaging of electrocardiographic waveforms in these patients. PMID- 1927948 TI - Clinical and electrophysiologic characteristics of exercise-related idiopathic ventricular tachycardia. AB - In 37 (70%) of 53 patients with idiopathic ventricular tachycardia (VT), episodes were mainly related to exercise (group 1). These patients were younger (33 +/- 14 vs 44 +/- 18 years, p = 0.015) and more often had dizziness during VT (71 vs 40%, p = 0.003) than the 16 patients in whom VT was not exercise-related (group 2). Patients in group 1 needed cardioversion less often to terminate the arrhythmia (4 (11%) vs 6 (40%), group 2 [p = 0.04]). VT was initiated during exercise testing in 62% of patients in group 1 but in only 1 patient in group 2 (p = 0.0004). Induction of clinical VT during programmed stimulation was observed in a similar percentage in group 1 (49%) and group 2 (50%) patients. Isoproterenol infusion facilitated the induction of VT in 9 of 20 (45%) group 1 and in 2 of 8 (25%) group 2 patients (p = not significant). After a mean follow-up of 2.9 +/- 2.5 years, 8 (22%) group 1 patients and 5 (31%) group 2 had at least 1 episode of symptomatic VT. Only 1 patient died suddenly. Class III drugs were the most useful in preventing recurrences. Beta-blocking agents were of little value in both groups. Patients with VT and a structurally normal heart have a good prognosis despite recurrences of their arrhythmia. The relation of the arrhythmia to exercise has no prognostic implications. PMID- 1927950 TI - A cellular transtelephonic defibrillator for management of cardiac arrest outside the hospital. AB - A cellular transtelephonic defibrillator facilitates early defibrillation in remote areas and involves electrocardiographic diagnosis and defibrillation control by a physician remote from but in voice contact with the patient-unit operator. The patient unit contains a microprocessor, microphone, defibrillator, electrocardiogram/defibrillator electrode pads and cellular telephone. Activation of the patient-unit initiates automatic dialing and contact with the remotely sited base station within 35 to 50 seconds. The physician at the base station identifies the rhythm and controls defibrillator charging and discharge. The minimal interaction required between the system and the local operator makes it suitable for use by minimally trained first responders. The cellular transtelephonic defibrillator has been tested in 211 calls responded to by a physician-manned mobile coronary care unit over distances up to 15 miles in an urban area. Satisfactory electrocardiographic transmission and voice communication were established in 172 of 211 calls (81.5%). In 39 (18.5%), connection with the base station either could not be established or maintained mainly because of geographic location or battery failure. One hundred direct current shocks of 50 to 360 J were effectively administered to 22 patients with 48 episodes of ventricular fibrillation or ventricular tachycardia with successful correction of 46 of 48 episodes using 1 to 4 shocks per episode. Widespread distribution of such devices could improve survival in patients with cardiac arrest outside the hospital. PMID- 1927951 TI - Lack of reproducibility of frequency versus time domain signal-averaged electrocardiographic analyses and effects of lead polarity in coronary artery disease. AB - Time domain signal-averaged electrocardiographic parameters have been found to be consistent over the short term. Similar data have not been verified for the frequency domain. In addition, the effects of lead polarity changes on time domain or frequency domain parameters are not known. Signal-averaged electrocardiography was performed on 15 patients using the Arrhythmia Research Technology model 1200 EPX with orthogonal X, Y and Z leads. Time domain variables included filtered QRS, root-mean-square voltage of the last 40 ms of the QRS and duration of signals less than 40 microV. Two frequency domain area ratios were analyzed: a 140-ms window including last 40 ms of QRS + 100 ms of ST; and a 140 ms window beginning at QRS onset (both 20 to 50/0 to 20 Hz). Values were compared for each lead, as well as for a vector composite and the arithmetic mean of the 3 leads. Each patient underwent 3 studies performed 5 minutes apart. The polarity of the X lead was reversed between the first and second studies, and then returned to standard for the third study. Time domain variables correlated closely among the studies irrespective of lead polarity, with r values of 0.993 to 1.000 (p less than 0.0001). Frequency domain parameter correlation was much poorer, with r values as low as 0.276. Frequency domain correlations between tests 1 and 2 and 2 and 3 (mean r = 0.778) were poorer than between tests 1 and 3 (mean r = 0.829), implying an effect of lead polarity change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927952 TI - Effectiveness of percutaneous balloon mitral valvotomy during pregnancy. AB - During pregnancy, medically refractory congestive heart failure due to mitral stenosis continues to present a clinical challenge and optimal management remains controversial. Thirteen women underwent balloon mitral valvotomy for control of functional class III or IV congestive heart failure due to mitral stenosis during pregnancy. The mean gestational age at the time of valvotomy was 25 +/- 6 weeks. Percutaneous balloon mitral valvotomy was performed successfully in all patients. No maternal or fetal mortality occurred. The mean mitral valve area assessed by Doppler echocardiography increased from 0.9 +/- 0.3 cm2 before to 2.1 +/- 0.3 cm2 after valvotomy. The mean mitral valve gradient decreased from 20 +/- 7 to 4 +/- 2 mm Hg. This was associated with a decrease in the pulmonary artery systolic pressure from 62 +/- 24 to 32 +/- 14 mm Hg. Currently, 12 of the 13 patients have delivered at an average gestational age of 38 +/- 0.5 weeks. Symptoms of congestive heart failure improved in all women and all were in New York Heart Association functional class I at the time of delivery. One patient is still pregnant and symptom free. Eleven singlet pregnancies resulted in the birth of full-term, healthy infants (mean birth weight 3.2 kg). The woman carrying a twin pregnancy improved from New York Heart Association class IV to class I after balloon mitral valvotomy but delivered prematurely at 32 weeks. The premature twin infants weighed 1.0 and 1.5 kg and died from respiratory failure at 48 hours. Percutaneous balloon mitral valvotomy can be performed safely during pregnancy and is effective in relieving symptoms of severe congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927954 TI - Effects of percutaneous mitral valvuloplasty on left ventricular mass and volume. AB - The response of left ventricular (LV) geometry to altered loading conditions after mitral valvuloplasty has been incompletely described. Therefore, 15 patients with rheumatic mitral stenosis were studied using quantitative 2 dimensional echocardiography a mean of 1 +/- 2 months before and 11 +/- 5 months after percutaneous balloon mitral valvuloplasty. Mitral valve area (Gorlin) increased in all patients, from 1.0 +/- 0.3 to 1.9 +/- 0.5 cm2 (p less than 0.01). Mitral regurgitation (1+/4+) developed in 3 patients, and increased by 1 grade in 1 patient as a consequence of mitral valvuloplasty. After valvuloplasty, there were significant increases in LV end-diastolic volume (69 +/- 22 to 82 +/- 26 ml, p less than 0.01), stroke volume (34 +/- 13 to 46 +/- 19 ml, p less than 0.05) and mass (181 +/- 46 to 200 +/- 42 ml, p less than 0.005). LV end-systolic volume and ejection fraction did not change significantly. LV mass-to-volume ratio was unchanged (5.6 +/- 1.5 to 5.8 +/- 1.4 g/ml, p = not significant). Quantitatively similar results were obtained when these changes were indexed to body surface area. Thus, successful mitral valvuloplasty was associated with significant increases in LV end-diastolic volume and mass. These findings suggest that increased preload may be a stimulus to myocardial growth. PMID- 1927953 TI - Effects of long-term vasodilator therapy on electrocardiographic abnormalities in chronic aortic regurgitation. AB - Electrocardiographic abnormalities develop in patients with chronic aortic regurgitation (AR). Although vasodilator drugs may reduce left ventricular (LV) volume overload, the effects of such therapy on electrocardiographic abnormalities have not been previously evaluated. Accordingly, electrocardiograms were analyzed before and after double-blind, randomized administration of either hydralazine or placebo in 54 patients with chronic AR. These patients were without limiting symptoms and had preserved ejection fraction on entry in the study. The magnitude of ST-segment depression and Romhilt-Estes point score for LV hypertrophy were assessed. Baseline ST depression and LV hypertrophy scores in the placebo and hydralazine groups were not significantly different. At follow up, after a mean of 19 +/- 6 months, there was a significant reduction in ST depression in patients taking hydralazine (n = 28) compared with patients given placebo (n = 26): -0.023 +/- 0.044 vs 0.029 +/- 0.055 mV, respectively (p = 0.0001); and in the LV hypertrophy score (-1.1 +/- 2.2 vs 0.9 +/- 2.3 points, respectively; p = 0.002). Hydralazine-treated patients also had significant decreases in LV end-diastolic and end-systolic volume indexes, and a significant increase in ejection fraction. These results suggest that such vasodilator therapy may be beneficial in patients with chronic AR. PMID- 1927955 TI - Effects of exercise on left ventricular diastolic performance in trained athletes. AB - Dynamically trained athletes develop increased left ventricular (LV) wall mass. To determine whether this increased wall mass impaired characteristics of LV diastolic filling, serial Doppler echocardiograms were obtained from 10 trained athletes (mean age 21 years) at rest, during supine graded bicycle exercise and during recovery at heart rates of 80, 120 and 140 beats/min, respectively. Similar studies were obtained in 10 age-matched control subjects. Studies at rest showed significant increases in athletes in LV end-diastolic dimension and indexed LV wall mass. Differences in peak filling rates and in normalized peak lengthening rates between athletes and control subjects were seen at heart rates of 140 beats/min during exercise and recovery. Differences in Doppler-derived variables between athletes and control subjects were seen in total time-velocity integral, early peak filling velocity and E/A ratio. In athletes, time-velocity integral was increased during recovery at heart rates of 120 beats/min and 80 beats/min, early peak filling velocity was increased during exercise at 120 beats/min and during recovery at 120 beats/min and 80 beats/min, and E/A ratio was higher at all heart rates during both exercise and recovery. Although no significant differences were found in LV diastolic filling indexes at rest, a significant enhancement was found in these parameters in dynamically trained athletes during exercise, particularly at higher levels of dynamic exercise. PMID- 1927956 TI - Age-related changes in aortic elasticity determined by gated radionuclide angiography in patients with systemic hypertension or healed myocardial infarcts and in normal subjects. AB - We estimated the aortic volume elasticity (Ve), an index of aortic stiffness, using gated radionuclide angiography, and investigated age-related changes in aortic elasticity in 22 normal control subjects, 30 hypertensive patients and 36 patients with old myocardial infarction. Ve elasticity was calculated noninvasively as a ratio of the pressure change (dP) and the percent volume change (dV/Vo) determined by radionuclide angiography [Ve = dP/(dV/Vo)]. dV/Vo was calculated from the maximal and minimal counts in the aortic arch [dV/Vo = (maximum - minimum)/minimum]. Ve increased significantly with age in normal control subjects (r = 0.62, p less than 0.001), hypertensive patients (r = 0.60, p less than 0.001) and patients with old infarcts (r = 0.59, p less than 0.001). The age-related increase in Ve was significantly greater in hypertensive patients, and that for patients with old myocardial infarcts tended to be greater than in control subjects. Thus, hypertension accelerates the decrease in aortic elasticity with aging. The greater decrease in aortic elasticity resulted in a significant age-related increase in pulse pressure in patients with hypertension and old myocardial infarction. PMID- 1927957 TI - Are we biased in our approach to treating elderly patients with heart disease? PMID- 1927958 TI - Value of the electrocardiogram for prediction of left ventricular mural thrombus in anterior wall acute myocardial infarction. PMID- 1927959 TI - Platelet function and plasma lipid levels in patients with stable and unstable angina pectoris. PMID- 1927960 TI - Two-dimensional echocardiographic characteristics of pericardial hematoma secondary to left ventricular free wall rupture complicating acute myocardial infarction. PMID- 1927961 TI - Can patients discriminate between atrial fibrillation and regular supraventricular tachycardia? PMID- 1927962 TI - Cause of acute myocardial infarction after successful coronary angioplasty. PMID- 1927963 TI - Sudden death due to ventricular tachycardia during amiodarone therapy in familial hypertrophic cardiomyopathy. PMID- 1927964 TI - Relation of clinical and angiographic factors to functional capacity as measured by the Duke Activity Status Index. PMID- 1927966 TI - Hematocrit fluctuations after percutaneous transluminal coronary angioplasty. PMID- 1927967 TI - Dynamics of atrioventricular nodal conduction ratios during conversion of 2:1 into 3:1, 4:1 and 5:1 atrioventricular block. PMID- 1927965 TI - Dobutamine stress echocardiography for assessment of cardiac risk before noncardiac surgery. PMID- 1927968 TI - Initial migration and distribution of the cardiac neural crest in the avian embryo: an introduction to the concept of the circumpharyngeal crest. AB - The distribution and migration of the cardiac neural crest was studied in chick embryos from stages 11 to 17 that were immunochemically stained in whole-mount and sectioned specimens with a monoclonal antibody, HNK-1. The following results were obtained: 1) The first phase of the migration in the cardiac crest follows the dorsolateral pathway beneath the ectoderm. 2) In the first site of arrest, the cardiac crest forms a longitudinal mass of neural-crest cells, called in the present study, the circumpharyngeal crest; this mass is located dorsolateral to the dorsal edge of the pericardium (pericardial dorsal horn) where splanchnic and somatic lateral mesoderm meet. 3) A distinctive strand of neural-crest cells, called the anterior tract, arises from the mid-otic level and ends in the circumpharyngeal crest. 4) By stage 16, after the degeneration of the first somite, another strand of neural-crest cells, called the posterior tract, appears dorsal to the circumpharyngeal crest. It forms an arch-like pathway along the anterior border of the second somite. 5) The seeding of the pharyngeal ectomesenchyme takes place before the formation of pharyngeal arches in the postotic area, i.e., the crest cells are seeded into the lateral body wall ventrally from the circumpharyngeal crest; and, by the ventral-ward regression of the pericardial dorsal horn, lateral expansion of pharyngeal pouch, and caudal regression of the pericardium, the crest cell population is pushed away by the pharyngeal pouch. Thus the pharyngeal arch ectomesenchyme is segregated. 6) By stage 14, at the occipital somite level, ventrolateral migration of the neural crest is observed within the anterior half of each somite. Some of these crest cells are continuous with the caudal portion of the circumpharyngeal crest. An early contribution to the enteric neuroblasts is apparent in this area. PMID- 1927969 TI - The sinoatrial ring bundle: a cardiac neural communication system? AB - The sinoatrial ring bundle (SARB), was originally described as a "whitish bundle of tissue which describes an almost complete loop around the two venae cavae and the coronary sinus" in the adult rabbit heart (Paes de Carvalho et al., 1959). The histologically and electrophysiologically differentiated structure, derived from the embryonic venous valves, was suitably placed for rapid conduction from sinoatrial (SA) to atrioventricular (AV) node, but no evidence was found for this role. Today, the function of the SARB remains obscure. Cholinesterase/silver staining reveals the neural pattern associated with the SARB and suggests a function. Throughout its extent, the SARB contains a bundle of parallel muscle fibers and accompanying long nerves. The nerves distribute to structures at either side of the loop: superolaterally to pectinate muscle and inferomedially to the region of the AV node. Along the curve of the right SARB, the nerves contribute to a dense neural plexus with nerves coiled around muscle. The plexus communicates with the nearby SA node and with the ganglia inferior to the node near the inferior vena cava. The morphological pattern of neural elements is suitably organized to suggest tension monitoring and internodal, neural communication. PMID- 1927970 TI - Organization of tubules in the human caput epididymidis and the ultrastructure of their epithelia. AB - The structure of the human caput epididymidis was examined by gross morphological and light and electron microscopic techniques. There were at least seven types of tubules, each characterized by a different epithelium. These tubules were connected with one another by at least eight types of junctions to form a network. Most of the caput epididymidis was composed of efferent ducts. Within these, five types of tubules, each with a different ciliated epithelium, were found in different regions; and four types of junctions between the efferent ducts and the epididymal tubule were observed. The efferent ducts left the testis, initially as parallel straight tubules containing both ciliated and non ciliated cells in an epithelium of irregular height. Each efferent duct then coiled tortuously into lobules that folded over one another. These efferent ducts then branched out as thin tubules to join a network of dark tubules which were lined by a regular epithelium containing prominently vacuolated, non-ciliated cells. These tubules anastomosed via common cavities characterized by a ciliated cuboidal epithelium and sometimes joined tubules exhibiting a non-vacuolated ciliated epithelium. The latter, as well as typical efferent ducts, made connection with the epididymis proper in both end-to-end and end-to-side junctions. In the more distal junctions with the epididymis, the efferent ducts joined to a transitional epididymal ductule before joining to the side of the epididymis proper. Post-junctional epithelia in the beginning of the epididymis occasionally contained patches of cells characteristic of efferent ducts. Tall cells with long stereocilia constituted a discontinuous "initial segment"-like region of the epididymis. This is the most detailed study so far of the epithelia and the tubule organization in the caput epididymidis of any species, and most of the results are reported for the first time for the human. Although the pattern of the tubule network resembles that of some domestic species, the rich variety of epithelia has not been appreciated before. PMID- 1927971 TI - Auditory epithelial migration. III. Development of the stratified squamous epithelium of the tympanic membrane and external canal in the mouse. AB - The development of the stratified squamous epithelium of the tympanic membrane and external auditory canal was studied in serial sections of 124 mouse ears aged from 11 gestational days to 100 days. A fold developed from the edge of the fundus of the primary canal. It possessed two regions: firstly the meatal plate, which produced the pars tensa-covering epithelium (zone 2) and most of the deep ear canal epithelium (zone 3), and secondly the fundal extension plate, which grew from that part of the fundus not forming the meatal plate. The fundal extension plate gave rise to the pars flaccida-covering epithelium (zone 1) and also to the adjacent deep canal epithelium (zone 3). A difference from human development was that zone 3 in the mouse, in both the meatal plate- and the fundal extension plate-derived areas, formed adnexal structures. In the early development of the meatal plate, zone 3, at its tip, was swollen and actively mitotic and extended always for a short distance on to the zone 2 side. Zone 2, first perceived two days after zone 3, became progressively attenuated, and by the fourth day after its formation was a single thin layer. It is suggested that the proximal part of zone 3, situated in the mature ear around the periphery of the tympanic membrane, is a generation center for unidirectional outward flux of epithelium which terminates in the mouse at the first adnexal structure. It may cause the whole of zone 2 to move in the same direction by negative contact inhibition. PMID- 1927972 TI - An immunohistochemical study of the GnRH neuron morphology and topography in the adult female rabbit hypothalamus. AB - The morphology and distribution of immunoreactive (GnRH) neural elements in the hypothalamus of the adult nulliparous female rabbit were examined. Approximately 1,000 GnRH cells (range 890-1136) were counted in the right half of the hypothalamus. Two distinct GnRH cell types were observed: GnRH cells with rough or spiny contours accounted for 64% of the total immunoreactive cells, and smooth contoured cells represented 34% of the total. The majority of immunoreactive neural elements were found in the anterior hypothalamus. GnRH cells and processes were located primarily in the ventral and medial anterior hypothalamus forming an inverted V pattern. Processes were followed from the medial preoptic area and suprachiasmatic nucleus to the infundibular stem. Extrahypothalamic projections of GnRH cells were observed. Immunoreactive fibers were also found to contact the ependymal lining of the third ventricle. It is concluded that two morphologically distinct GnRH cell types exist and have a broad distribution in the rabbit hypothalamus. The functional significance of these cell types requires further study. PMID- 1927973 TI - Bone marrow: a site for hemopoietic precursor cell development. Introduction to the symposium on bone marrow: a site for hemopoietic precursor cell development. PMID- 1927974 TI - Immunological mutants of the mouse. AB - Mutations at more than 30 loci in mice have been shown to cause deleterious effects on the immune system. Immunologic defects caused by certain of these mutations are determined at the level of hematopoietic progenitor cells or at the level of hematopoietic cell-stromal cell interactions. The immunological mutants described in this paper serve as experimental tools with which to increase our understanding of the development and regulation of the mammalian immune system. PMID- 1927975 TI - Sequence-specific binding of a c-myc nuclear-matrix-associated region shows increased nuclear matrix retention after leukemic cell (HL-60) differentiation. AB - HL-60 cells, a human promyelocytic leukemia cell line, contain amplified c-myc DNA sequences and mRNA transcripts. These cells can be induced to undergo macrophage differentiation by phorbol esters, which results in suppression of c myc expression and cessation of cell proliferation. The nuclear matrix (NM), a nuclear skeleton resistant to DNase I digestion and high salt extraction, is proposed to be involved in DNA replication, gene regulation, and the correct distribution of DNA at mitosis. We have previously identified a nuclear-matrix associated region (MAR) of the c-myc protooncogene to reside in a 1.4-kb region between Cla I and Eco RI restriction sites at the 3'-end of the gene. A 172-bp Dra I/Dra I subfragment of the 1.4-kb region was shown to be a major component of the MAR (myc-MAR), and this subfragment was demonstrated to be recognized by a nuclear protein (p25). In this report we demonstrate that phi X174 DNA, or the synthetic copolymers poly[d(G.C)] and poly[d(A.T)], are not effective suppressors of the binding of the myc-MAR to isolated NM, indicating that the binding sequence(s) are unique. We find that the addition of partially purified protein p25 increases the relative affinity of the myc-MAR for HL-60 NM in an in vitro assay system. NM isolated from HL-60 macrophages induced by phorbol esters retains significantly more myc-MAR DNA fragment in the presence of an excess amount of competitor DNA than does NM from untreated HL-60 cells. These data suggest that a change of the myc-MAR association with the NM occurs after monocytic differentiation of HL-60 cells. PMID- 1927976 TI - Bone marrow-thymus axis in senescence. AB - This presentation offers a brief review of the bone marrow-thymus axis in senescence, a putative model for thymocyte differentiation, and recent results of our work on the status of pre-thymic stem cells in aged mice. The data presented here provide further evidence for a thymus endocrine influence on the bone marrow stem cells, specifically lymphocyte precursors. It has been postulated that the thymic hormones may act on lymphocyte precursors in the bone marrow and that the loss of thymic factors during senescence may be a contributing factor to the decreased cellular immune function. This study used Haar's in vitro model to investigate the bone marrow-thymus axis in aged mice. Erythroid-depleted bone marrow cells from 3-month- and 24-month-old CBA (Thy 1.2) mice were placed in the upper half of a blind-well chamber with thymus supernatant in the lower half. Experimental cells were treated with thymus supernatant for 1 hr prior to migration. This study confirmed that pre-thymic stem cells in aged bone marrow are deficient in their ability to migrate to the thymus supernatant. It also revealed that treatment of the old bone marrow with thymus supernatant, made from neonatal thymus cultures, could dramatically improve the thymus migrating ability of the aged bone-marrow stem cells. PMID- 1927977 TI - Treatment of bilateral cleft lip and palate. PMID- 1927979 TI - Removal of ceramic brackets. PMID- 1927978 TI - The use of silicone elastomeric positioner-type appliances in space closure: three case reports. PMID- 1927980 TI - Functional appliances--a valuable tool in your armamentarium. PMID- 1927981 TI - Soft-tissue and dentoskeletal profile changes associated with mandibular setback osteotomy. AB - The aims of the present retrospective cephalometry study were (1) to describe the interrelationships of the soft-tissue and dentoskeletal profiles after total mandibular setback osteotomies and (2) to detect whether there were any cephalometric variables that could contribute to an accurate prediction of the surgical effect on the soft-tissue profile. The presurgical and postsurgical lateral cephalograms of 50 consecutively treated patients (37 females and 13 males) were used; these patients had received combined orthodontic-surgical management of mandibular prognathism by means of a bilateral vertical ramus osteotomy with an extraoral approach. At the time of surgery, their ages ranged from 17 to 41 years. Lateral cephalograms with the teeth in habitual occlusion taken before and approximately 1 year after surgery were available for all patients. A computerized cephalometric appraisal, named profile analysis, was developed and used, including variables corresponding to sagittal and vertical relationships of skeletal and soft-tissue profiles, incisal relationships, soft tissue thickness, and lip morphology. The statistical elaboration of the data was made by means of paired t test, Pearson's product-moment coefficient correlation, and multiple regression analyses. The assessment of the results disclosed that considerable facial changes and improvement took place after the surgical procedure. The skeletal and soft-tissue facial profiles were straightened and the posture of the lips was improved. The normal incisal relationship achieved became influential on the soft tissues overlying both incisors and led to a better lip competence and posture. Posterior movement at points B and Po was accompanied by reductions ranging from 91% to 103% of the corresponding soft tissues. The presence of both significant correlation coefficients (p less than 0.05) and high r square values (greater than 0.70) in the multiple regression analysis for the osseous tissue variables N-B and N-Po, alone or together with the overjet and S-N B angle, respectively, reflected their high prediction value with regard to the sagittal relationship of the lower lip, its thickness, and the soft-tissue thickness at the chin area. The findings of Pearson's product-moment coefficient correlation also indicated that the operative changes of the thickness of the upper lip, the lower lip, and the soft tissue at the chin region are influenced by the initial preoperative thickness of the area. PMID- 1927982 TI - The effects of a 0.12% chlorhexidine gluconate mouthrinse on orthodontic patients aged 11 through 17 with established gingivitis. AB - The purpose of this study was to assess the effectiveness of a 0.12% chlorhexidine gluconate (CH) mouthrinse, Peridex, on orthodontic patients 11 through 17 years of age with established gingivitis. Thirty-four subjects were divided into two groups (CH and placebo) of 17 subjects each on the basis of gender, and they were evaluated at baseline, at 6 weeks, and at 12 weeks in a double-blinded manner. The gingival index (GI) of Loe and Silness, the plaque index (PI) of Silness and Loe, the Eastman Interproximal Bleeding Index, and the CWRU staining index were recorded for each subject. The subjects in the CH group, as compared with the placebo group, had statistically significant reductions, expressed as percent reductions against baseline, at the conclusion of this 3 month period: PI = 64.9%, GI = 60.0%, and gingival bleeding = 77.2%. Staining was in the moderate range, and it was concentrated on the mandibular lingual surfaces. Peridex, in combination with mechanical plaque removal, proved to be an important therapeutic agent in controlling gingival inflammation, bleeding, and plaque accumulation in orthodontic patients 11 through 17 years of age with established gingivitis. PMID- 1927983 TI - Lip bumper therapy for gaining arch length. AB - With the use of pretreatment and posttreatment lateral cephalograms and study models, lip bumper therapy for two groups of 20 patients was evaluated. One group was treated with lip bumpers fabricated from stainless steel round wire covered with shrink tubing and activated every 2 to 3 months. The second group was treated with larger prefabricated lip bumpers covered with acrylic shields from canine to canine and activated every 4 to 5 weeks. Yearly rates of treatment change indicate that the type of lip bumper used and the method of clinical manipulation have no effect on mandibular incisor position. Both groups showed similar rates of controlled incisal tipping with the center of rotation at the apex. Dental movements of the posterior segment were significantly different between groups. The second group displayed significantly more molar tipping than the first group. The second group also showed significantly greater transverse expansion of the canines, first premolars, and first molars. PMID- 1927984 TI - Effects of orthodontic attachments on the gingival health of permanent second molars. AB - The aim of this study was to evaluate the effect of cemented bands and enamel bonded attachments on the gingival health of second molars. In 23 patients the right upper and lower second molars were banded, while the left upper and lower second molars were bonded. The plaque index, the gingival index, and pocket depths were greater and statistically significant on the right side, indicative of increased inflammatory activity where bands were cemented. Once the appliances were removed, both areas returned to pretreatment levels. PMID- 1927985 TI - Static frictional force and surface roughness of nickel-titanium arch wires. AB - Surface roughness and static frictional force resistance of orthodontic arch wires were measured. Nine nickel-titanium alloy arch wires were studied. One beta titanium alloy wire, one stainless steel alloy wire, and one cobalt-chromium alloy wire were included for comparison. Arithmetic average roughness in micrometers was measured with a profilometer. Frictional force resistance was quantified by pushing wire segments through the stainless steel self-ligating brackets of a four-tooth clinical model. The cobalt-chromium alloy and the nickel titanium alloy wires, with the exception of Sentalloy and Orthonol, exhibited the lowest frictional resistance. The stainless steel alloy and the beta-titanium alloy wires showed the highest frictional resistance. The stainless steel alloy wire was the smoothest wire tested, whereas NiTi, Marsenol, and Orthonol were the roughest. No significant correlation was found between arithmetic average roughness and frictional force values. PMID- 1927986 TI - The pain experience and psychological adjustment to orthodontic treatment of preadolescents, adolescents, and adults. AB - Age-related changes in psychological measurements of pain and well-being were studied in patients undergoing full fixed appliance orthodontic treatment. A longitudinal series of four questionnaires was used to obtain measurements of these factors after the separation phase of treatment, banding (2 to 7 days after separation), the first adjustment visit (3 to 4 weeks after placement of full fixed appliances), and the second adjustment visit (3-4 months after banding was completed). The results suggest an interaction between the phases of treatment and reported pain and psychological well-being and significant differences in the response profiles of the adolescent age group (14 to 17 years) compared to the preadolescent (11 to 13 years) and adult groups (18 years and older). These findings did not appear to be due simply to group differences in the use of analgesics, class of malocclusion, or type of full fixed appliance used. The profile comparisons indicated that the adolescent age group generally reported lower levels of psychological well-being and higher levels of pain during the phases of treatment examined. Consistent with these results was the finding that the adolescents differed from the preadolescents and adults in the quality of the pain experience reported during treatment. The results indicate an age difference in adjustment to fixed orthodontic therapy, which suggests that adolescents are more vulnerable to undesirable psychological effects of treatment. PMID- 1927987 TI - Cartilage matrix production and chondrocyte enlargement as contributors to mandibular condylar growth in monkeys (Macaca fascicularis). AB - In an attempt to determine the contributions to condylar growth of cartilaginous matrix production and chondrocyte enlargement, four prepubertal male monkeys (Macaca fascicularis) were used. Each animal received 1 mCi 3H-proline per kilogram of body weight 24 hours before death. From the left condyles, the anterior and central segments of the growth cartilage in the lateral and medial joint region were examined with the light microscope. Volumes of cells and extracellular matrix, as well as the intensity of radioautographic labeling, were estimated stereologically in four layers from the articular surface to the zone of endochondral ossification. On the assumption of a steady-state system, these data led to the conclusion that an average chondrocyte in the anterior segment of the growth cartilage contributed to condylar growth by about 3000 microns 3 of newly formed matrix and about 1000 microns 3 of increased cell size. The respective estimates in the central segment were about 3700 microns 3 and 2000 microns 3. Thus, unlike findings in the condylar cartilage of 20-day-old rats, matrix production in the simian condyle exceeded chondrocyte enlargement, although in varying ratios of about 3:1 anteriorly and 1.85:1 centrally. On the other hand, chondrocyte enlargement from the anterior segment to the central segment increased by about 100%, while the increase of about 25% in matrix production was outweighed by variation between individual animals. These findings suggest that the relative contribution of the two growth components varies considerably, on the one hand, with the species or possibly with the stage of condylar development examined and, on the other hand, between various anteroposterior locations within the condylar cartilage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1927988 TI - The skeletodental adaptations in deep bite correction. AB - The purpose of this study was to analyze the skeletal and dental changes produced by orthodontic correction of a deep bite. A comparison was made between the adolescents' and the adults' responses in an attempt to observe any differences that accounted for increased stability in a growing patient. Records on 30 patients were analyzed before and after treatment. These patients were divided into two equal groups on the basis of their stage of maturational development. The group of "growers" had an average age of 12.2 years, and the group of "nongrowers" averaged 26.7 years in age. All represented nonextraction cases with an excessive overbite before treatment. Deep bite was corrected by leveling with conventional continuous arch wires. Cervical headgear, Class II, or vertical elastics were used when indicated. On the average, the molars were extruded 4.7 mm in the grower's group. However, the mandibular plane angles did not change during treatment. This finding can be attributed to the greater amount of posterior mandibular development that was observed in growing patients. Even with minimal extrusion of the molars (1.3 mm on average), the adults did not maintain the original mandibular plane angle. PMID- 1927990 TI - Health care for uninsured and underinsured children. PMID- 1927989 TI - The case of the wrong tooth. AB - As can be seen from this report, multifactorial considerations are often present in an orthodontic case. Office policy considerations regarding interoffice communications should be reviewed periodically as to their sufficiency. Interpersonal communications are vitally important from both a risk management standpoint and also from the perspective of maintaining a good doctor-patient relationship. Practitioners today need to keep a wary eye open regarding all possible treatment alternatives, even bizarre ones, should the clinical situation dictate the need for them. Good recordkeeping and documentation are omnipotent should one have the need to defend one's actions. This applies not only to radiographs, photographs, and treatment charts but to records of third-party conversations as well. The doctrine of informed consent should act as a guideline to what information need be transmitted to the patient, both at the beginning and throughout treatment, as it can often help calm potentially troubled waters. Finally, a little luck never hurt anybody. PMID- 1927991 TI - Parental drinking habits. PMID- 1927992 TI - Cholesterol testing in the physician's office: accuracy assessment. PMID- 1927993 TI - Formula companies and the medical profession. PMID- 1927994 TI - Scoring systems for accurate prognosis of patients with meningococcal infections. PMID- 1927995 TI - Association of alkaline urine with eating disorders. PMID- 1927996 TI - Reexpansion pulmonary edema. PMID- 1927997 TI - Nintendo enuresis. PMID- 1927998 TI - Mitral valve prolapse: back to the basics. PMID- 1928000 TI - House staff work hours and moonlighting: what do residents want? A survey of pediatric residents in California. AB - In the autumn of 1988, pediatric residents were surveyed on attitudes toward work hours, moonlighting, and priorities in regulation of working conditions. Questionnaires for all 756 California residents in accredited pediatric programs were sent to chief residents. Of these, 676 questionnaires were distributed to residents and 319 (47%) were returned. Respondents indicated strong support for limits on house staff working hours, and most approved of the reduction regulations proposed in New York State. Most believed that individual departments, hospitals, or subspecialties should regulate hours. By a ratio of 4.3:1, however, respondents favored legislative intervention if such limits were not set by the profession. Moonlighting was generally considered to be an individual's choice and responsibility, but a majority were willing to restrict moonlighting if total house staff hours were also limited. PMID- 1927999 TI - Endotoxin concentrations in cerebrospinal fluid correlate with clinical severity and neurologic outcome of Haemophilus influenzae type B meningitis. AB - Endotoxin concentrations were measured in paired samples of cerebrospinal fluid from 38 patients with Haemophilus influenzae type b meningitis. On admission, the median concentration of endotoxin in cerebrospinal fluid was 104 ng/mL and decreased rapidly in follow-up samples. From 17 to 48 hours after admission, 50% of the patients had concentrations of less than 1 ng/mL. Endotoxin concentrations correlated significantly with concentrations of interleukin 1 beta, protein, and glucose in cerebrospinal fluid, duration of secondary fever, and neurologic abnormalities during hospitalization and on follow-up examinations. Twenty-eight percent of patients with endotoxin concentrations of 100 ng/mL or more on admission had long-term complications, compared with none of those with lower endotoxin concentrations (relative risk, 2.31; 95% confidence interval, 1.53 to 3.48). These results indicate that quantitation of endotoxin in cerebrospinal fluid could be a valuable aid in identifying those children at increased risk of complications during Haemophilus influenzae type b meningitis and provide additional evidence that the Haemophilus influenzae type b meningitis lipo oligosaccharide is important in the pathogenesis of meningitis. PMID- 1928001 TI - Barriers to medical care for homeless families compared with housed poor families. AB - To evaluate health access and health services utilization of homeless families we selected a systematic sample of 194 homeless families from 10 shelters in Los Angeles and 196 housed poor families from the same geographic regions of Los Angeles selected from welfare offices. Both samples relied primarily on Medicaid for their health insurance (61% and 96%). However, more homeless families than housed poor families were currently uninsured (26% vs 2%), had lost health insurance over the past year (50% vs 21%), and had spent a greater percentage of the past year uncovered by health insurance (22% vs 6%). Homeless families were much less likely to report a regular provider for preventive care (81% vs 94%) or for sick care (72% vs 95%). Moreover, of those reporting a regular provider, homeless families were more likely than housed poor families to use emergency departments or clinics rather than private offices for both preventive care (35% vs 15%) and sick care (37% vs 26%). Barriers to health care more frequently prevented homeless families from obtaining care (38% vs 28%). These findings suggest that homeless families have greater problems of access to health care than other poor families, related to lack of insurance, lack of a regular primary care provider, and other barriers. Programs to address these barriers for homeless families are presented. PMID- 1928002 TI - Adolescents' attrition from school-sponsored sports. AB - This study investigated reasons for adolescents' attrition from school-sponsored sports teams and the relationship between attrition and intention to participate in organized and nonorganized sports in the future. Of 674 high school student athletes, 26% dropped off at least one team in 1989-1990, and overall attrition increased to 29.8% when attrition from more than one sport was considered. Attrition was higher among black students, students reporting an athletic injury, those injured playing football, and those sustaining a knee injury. Injury was cited as the most frequent reason for attrition, followed by being cut from the team, "other reasons," needing to get a job, inconvenient game or practice schedule, and needing more time to study, although the main reason for attrition also varied by sport. When athletes were classified according to externally precipitated attrition, athlete-initiated attrition, or completion of the sports season, no differences were noted in the three groups' intent to engage in organized sports in the future. However, the group with externally precipitated attrition expressed a stronger intent to engage in nonorganized sports in the future than the other two groups. PMID- 1928004 TI - Gastroesophageal reflux and apnea in prematurely born infants during wakefulness and sleep. AB - The hypothesis that acid gastroesophageal reflux may be responsible for the persistence of apnea was tested on 20 prematurely born infants, at a median conceptional age of 38.7 weeks. Gastroesophageal reflux was identified using distal esophageal pH monitoring. Apneas of durations greater than 10 seconds were identified and classified as either central or obstructive and mixed, using recordings of respiration. Wakefulness, active sleep, and quiet sleep were identified using electroencephalography and by assessing eye movements. Of 134 episodes of acid gastroesophageal reflux in the 20 subjects, more occurred during wakefulness and during active sleep than during quiet sleep. A total of 139 apneas, predominantly of the obstructive and mixed type, occurred. No relationship could, however, be demonstrated, in this rather small number of patients, between the occurrence of gastroesophageal reflux and that of apneas. PMID- 1928003 TI - Sun protection in newborns. A comparison of educational methods. AB - We investigated the effect of education on the sun exposure of newborns. Mothers of healthy newborns (n = 275) were enrolled in the spring of 1989 and interviewed by telephone in the fall of 1989. The mothers were divided into a control group, a low-level intervention group, and a high-level intervention group. Both the low level and high-level interventions succeeded in reducing the amount of time the newborns were allowed to spend in direct sunlight. Both types of intervention also resulted in reduced sun exposure time for the mothers. Although the number of mothers who used sunscreen was approximately the same in all three groups, when sunscreen use was controlled for, the intervention groups spent significantly less unprotected time in the sun than the control group. The mothers and newborns in both intervention groups simply spent less time outdoors. PMID- 1928005 TI - Oxygen saturation by pulse oximetry in healthy infants at an altitude of 1610 m (5280 ft). What is normal? AB - Pulse oximetry is a valuable, noninvasive technique for assessing oxygen saturation that has gained wide clinical acceptance despite little available information concerning normal values in the newborn, especially at an altitude different than sea level. We performed serial pulse oximetry studies on 150 term, appropriate-weight-for-gestational-age, clinically healthy infants at an altitude of 1610 m (5280 ft) at 24 to 48 hours, 1 month, and 3 months of age to define a reference range for oxygen saturation as a guideline in clinical care. We found that mean oxygen saturation at 24 to 48 hours of age is 92% to 93% and varies little with infant activity. With increasing postnatal age, there is a tendency for increased oxygen saturation during the awake states to 93% to 94%, while oxygen saturation during sleep stays the same or even decreases slightly. The lower end of the reference range (2 SDs below the mean) is as low as 85% during feeding at 24 to 48 hours of age, and as low as 86% during quiet sleep at 1 and 3 months of age, with 88% to 89% the lower limit in other activities at all ages. PMID- 1928006 TI - Posthemorrhagic hydrocephalus. Use of an intravenous-type catheter for cerebrospinal fluid drainage. AB - STUDY OBJECTIVE: To report a 9-year experience with the treatment of posthemorrhagic hydrocephalus (PHH) with the use of an easily inserted external ventricular drain. DESIGN: A case series with a retrospective review of hospital records and cranial ultrasound results, from 1981 through 1989, in all infants with PHH. INTERVENTION: A previously defined method of identification and bedside management of PHH was applied. If infants reached 2 kg of body weight and PHH recurred, a ventriculoperitoneal shunt was inserted. RESULTS: A total of 70 procedures were performed in 24 patients, and all were associated with a decrease in head circumference and ventricular size on ultrasound scan. One infection occurred, and only 12 infants required a ventriculoperitoneal shunt. CONCLUSIONS: This technique compared favorably with other methods of intervention to avoid early placement of a ventriculoperitoneal shunt in preterm infants and offered the advantage of consistently decreasing ventricular size. A multicenter controlled trial will be needed to compare the safety and efficacy of therapies for PHH. PMID- 1928007 TI - How much vitamin D for neonates? AB - To assess the adequacy of different dosages of neonatal vitamin D, 25 hydroxyvitamin D serum concentrations were longitudinally monitored in 27 low birth-weight and 25 full-term well infants from birth to 16 weeks after delivery. The infants were randomly assigned to receive either 10 micrograms/d (400 IU/d) or 20 micrograms/d (800 IU/d) of vitamin D or 0.85 or 1.5 micrograms/d of 25 hydroxyvitamin D3. In each infant who received 10 or 20 micrograms/d of vitamin D 25-hydroxyvitamin D, serum concentrations greater than 20 ng/mL were maintained, with some low-birth-weight infants reaching 60-ng/mL concentrations. Similarly, in the low-birth-weight infants receiving 1.5 and 0.85 micrograms/d of 25 hydroxyvitamin D3, serum 25-hydroxyvitamin D levels greater than 12 ng/mL were maintained. In the full-term infants who received 1.5 micrograms/d of 25 hydroxyvitamin D3, serum 25-hydroxyvitamin D concentrations of greater than 12 ng/mL were maintained, but in those who received 0.85 micrograms/d, serum 25 hydroxyvitamin D concentrations of 10 ng/mL could not be maintained. These vitamin D status data document that 10 micrograms (400 IU) of vitamin D represents a sufficient daily intake for both premature and full-term well infants. These data also indicate that while as little as 0.85 micrograms/d of 25 hydroxyvitamin D3 may facilitate vitamin D sufficiency in low-birth-weight neonates, it does not do so in full-term infants. PMID- 1928008 TI - Legalization of drugs of abuse and the pediatrician. AB - Growing numbers of individuals are proposing that drugs be legalized in the United States, with claims that federal, state, and local efforts to prohibit the use of illicit drugs are irrational and unenforceable. "Drug reform" advocates include persons of all political persuasions. Ironically, the call for drug reform comes at a time when trends in drug abuse, as reflected in national and state surveys, show a promising decline. It also is contradictory to at least one recent public opinion poll, in which respondents opposed the legalization of marijuana by a five-to-one margin. While their position is by no means unanimous, proponents of drug reform generally base their arguments on several key premises, such as elimination of or reductions in drug trafficking, enforcement, and interdiction expenditures; increased tax revenues from the legal sale of drugs; and reductions in health-care expenses associated with drug treatment. Reform advocates further claim that legalization would not be followed by an increase in drug use. The validity of each of these arguments is highly questionable. Legalization is a simplistic, short-sighted solution to a complex issue with public health, economic, criminal justice, and societal ramifications. Legalization would, moreover, abrogate the position taken in 1961 by the United States and 114 other nations in ratifying the United Nations Single Convention on Narcotic Drugs. The impact of drug reform merits an unbiased study by an independent agency. Until that time, pediatricians should inform themselves of the arguments for and against drug reform and be prepared to educate patients and their families about the issue. PMID- 1928009 TI - Radiological case of the month. Thorn-induced pseudotumor of the tibia. PMID- 1928010 TI - Picture of the month. Juvenile dermatomyositis. PMID- 1928011 TI - Growth hormone therapy in hypophosphatemic rickets. AB - The effects of growth hormone therapy on the biochemical measures of bone metabolism were studied in 11 children aged 3.5 to 17 years who had familial hypophosphatemic rickets; five were male. Subjects were maintained on a regimen of stable doses of conventional therapy (calcitriol and phosphate). Subjects were studied at baseline receiving conventional therapy and during three sequential treatment periods: no therapy (4 weeks), growth hormone only (0.05 mg/kg per day for 4 weeks), and conventional therapy plus growth hormone (2 weeks). The nine youngest subjects were continued on a regimen of triple therapy for an additional 24 weeks. Serum phosphate averaged 0.93 +/- 0.13 mmol/L (mean +/- SD) at entry and decreased when the subjects were not receiving any therapy. During the 4 weeks of growth hormone only treatment, phosphate rose in all 11 subjects (0.70 +/- 0.08 mmol/L to 0.83 +/- 0.08 mmol/L). With triple therapy, phosphate remained higher than with no therapy. Calcitriol, osteocalcin, and parathyroid hormone increased as the subjects received growth hormone alone. Insulinlike growth factor I z scores rose significantly in response to growth hormone therapy alone. All nine subjects receiving 6 months of triple therapy increased their growth rate z scores. Exogenous growth hormone therapy may be useful in familial hypophosphatemic rickets. PMID- 1928012 TI - Multilevel model to assess appropriateness of pediatric serum drug concentrations. AB - A multilevel model reviewing four assessment levels for pediatric serum drug concentrations was developed. Criteria for appropriate indication, sample collection, documentation, and utilization were based on therapeutic drug monitoring principles. The model was applied to 222 pediatric serum drug concentrations. Inadequate documentation was a major problem, but it occurred at a lower rate (37%) than previously reported. The rates of inappropriateness for indication (15%), sample collection (16%), and utilization (10%) were well within reported ranges but were significantly lower with pharmacy input. Overall, 48.2% of drug concentrations were inappropriate. Digoxin, phenobarbital, and aminoglycosides had the highest error rates. The annualized cost of inappropriate serum drug concentrations was $12,325. The described method allows for targeting of educational programs with defined areas for improvement. The findings of this study also support the involvement of clinical pharmacists in the therapeutic drug monitoring process. PMID- 1928013 TI - The association of pauciarticular juvenile arthritis and myasthenia gravis. AB - We encountered two children with fluorescent antinuclear antibody-positive pauciarticular juvenile arthritis who later developed myasthenia gravis. Acetylcholine receptor binding, blocking, and modulating antibodies, retrospectively tested on frozen serum, yielded negative results before the onset of myasthenic symptoms but all yielded strongly positive results coincident with the onset of weakness. In both children, myasthenia gravis responded to thymectomy, and one child had a beneficial response to plasmapheresis. Although, to our knowledge, only two patients with juvenile arthritis and myasthenia gravis have been described in the past, the presence of two additional children with both diseases in a single clinic population suggests that the association may be more prevalent than previously suspected. PMID- 1928014 TI - Minor malformations, hyperactivity, and learning disabilities. AB - Standardized minor malformation scores have been reported to predict and identify children with attentional problems and hyperactivity. The reason why this marker works for only a subset of children with attention deficit hyperactivity disorder remains unclear. The dysmorphology scores on all children presenting for a multidisciplinary team evaluation of developmental disorders were examined for diagnostic correlations after children with chromosomal disorders and recognized dysmorphic syndromes were excluded. For 1233 subjects, the mean minor malformation score was 2.94 (SD = 2.05). A significant association between minor malformation scores and IQ (mean = 80.95, SD = 23.67) was accounted for by the group with IQs greater than 100 exhibiting the higher dysmorphology scores. An analysis of variance revealed no significant association between minor malformation scores and hyperactivity or attention deficit disorder. Indeed, the presence of an attention deficit disorder yielded lower mean dysmorphology scores. When the minor malformation scores were compared for those subgroups of children with and without specific learning disabilities, the learning-disabled subjects had significantly higher dysmorphology scores. Minor dysmorphic features do not relate to the presence or absence of attentional problems or hyperactivity in referred children. Rather they appear to characterize that subpopulation of children with attention deficit disorder and learning disabilities as well as a group of learning-disabled children without attentional disorders. PMID- 1928015 TI - Resident, faculty, and residency program development. An integrated approach through annual retreats. AB - Retreats during residency training have evolved as an escape from the daily routine. Recognizing that the retreat format could also be used as a foundation for program design and personal development, we have designed annual retreats for each of the 3 years of pediatric residency training. The sessions vary in length and agenda, but serve as the basis for an ongoing effort fostering growth and maturation of the department and its component participants. The effectiveness of the program (and the morale of the residents) is greatly influenced by this program. PMID- 1928016 TI - Hand washing in pediatric ambulatory settings. An inconsistent practice. AB - The first phase of this study was performed to determine the rate of breaks in hand washing technique by physicians in two pediatric ambulatory settings and to determine whether this technique was influenced by the physician's level of training. The second phase was performed to determine if reminding physicians to wash their hands would decrease the rate of breaks. A hand washing break in technique was defined as not washing hands before patient contact. The observations were made by medical students accompanying the providers. In the 496 encounters during the first phase, 254 breaks (51.2%) occurred. In the 293 encounters during the second phase, 150 (51.2%) breaks occurred. During both phases, the rates of hand washing breaks among the four groups of providers (residents in postgraduate years 1 through 3 and faculty) were similar. Breaks in hand washing technique occur at an unacceptably high rate in outpatient settings. PMID- 1928017 TI - Immersion events in residential swimming pools. Evidence for an experience effect. AB - BACKGROUND: --Drowning and near-drowning in residential swimming pools are leading causes of morbidity and mortality for young children. We tested the hypothesis that the period immediately after a pool is acquired is a time of high risk for these events. This study was also designed to provide population-based data on swimming pool immersion events, regardless of severity. METHODS: --We conducted a mail survey of a probability sample of Sacramento County, California, households with in-ground swimming pools in January 1988; 80% of eligible subjects responded. Onset of exposure to a pool was defined as the month in which (1) the responding household had a pool installed, or (2) the responding household first occupied a residence with a pool. Exposures began in 1959 through 1987. RESULTS: --The home swimming pool immersion event rate was 11 per 1000 pool years. The rate per 1000 pool-years was higher for the first 6 months of exposure than thereafter (0 to 6 months, 44; 7 to 24 months, 14; greater than 24 months, seven), but 77% of events occurred outside the high-risk period. For households whose exposures began in 1984 through 1987, the immersion event rate was 51 per 1000 pool-years overall and 123 per 1000 pool-years for the first 6 months of pool exposure; these increases probably represent underreporting of earlier events. In this group, 48% of events occurred outside the high-risk period. The family swimming pool accounted for 91% of immersion events at the respondents' homes. CONCLUSIONS: --The residential swimming pool is an important hazard for pool-owning households. The first 6 months of exposure constitute a high-risk period, but many immersion events occur later. Pool drowning prevention programs may focus on newly acquired swimming pools and their owners but should be as broad as possible to maximize their effectiveness. PMID- 1928018 TI - Natural history of hematuria associated with hypercalciuria in children. AB - Hypercalciuria (HCU) is frequently found during the evaluation of children with hematuria; the long-term implications of untreated HCU in children are uncertain. Since 1981, we have identified HCU (urinary calcium, greater than 0.1 mmol.kg-1.d 1) in 58 patients (41 male) with hematuria; 64% had gross hematuria and 74% had a relative with urolithiasis. Renal HCU was diagnosed in 19 patients and absorptive HCU in 24 patients. In 15 children, the calcium loading test was nondiagnostic. In nine patients (16%), urolithiasis developed, and in one patient, a renal calcification developed. These 10 patients (seven male) were older (10.1 vs 7.5 years) than the other 48 patients and initially presented with gross hematuria (nine of 10). All 10 patients had a family history of urolithiasis. The initial urinary calcium value was similar between the 10 patients with stones (0.15 mmol.kg-1.d-1) and the patients without stones (0.14 mmol.kg-1.d-1); five had absorptive HCU and four had renal HCU. At least one follow-up urinary calcium measurement was available for 23 patients who were not receiving thiazide therapy during 1 to 6 years after diagnosis (mean, 3.1 years). At 1-year follow-up, 12 of 17 patients had HCU and five had hematuria. Twenty-one patients were studied 2 to 3 years from diagnosis; 11 had HCU and eight had hematuria. After 4 years, six of seven patients had HCU and three had hematuria. We concluded that children with HCU and hematuria are at significant risk for urolithiasis, especially if they have gross hematuria and a family history of urolithiasis. Hypercalciuria may be episodic in children with hematuria, and factors other than urinary calcium concentration may be responsible for urinary bleeding. PMID- 1928019 TI - A comparative trial of psychotherapies for ambulatory cocaine abusers: relapse prevention and interpersonal psychotherapy. AB - Despite the widespread use of psychotherapy as treatment for cocaine abuse, the effectiveness of psychotherapy has not been explored through clinical trials. Forty-two outpatients who met DSM-III criteria for cocaine abuse were randomly assigned to one of two forms of purely psychotherapeutic treatments of cocaine abuse, either relapse prevention (RPT) or interpersonal psychotherapy (IPT). Subjects assigned to relapse prevention were more likely than subjects in IPT to attain three or more continuous weeks of abstinence (57 versus 33%), be classified as recovered at the point of treatment termination (43 versus 19%), and complete treatment (67 versus 38%). Whereas these differences did not reach statistical significance, significant differences by treatment group did emerge when subjects were stratified by severity of substance use: Among the subgroup of more severe users, subjects who received RPT were significantly more likely to achieve abstinence (54 versus 9%) and be classified as recovered (54 versus 0%). Among the subgroups of subjects with lower severity of substance abuse, outcome was comparable for both treatment types. Comparison of results from this investigation with historical controls from a structurally similar pharmacotherapy trial suggests that purely psychotherapeutic treatments may be both viable and effective approaches for many ambulatory cocaine abusers. PMID- 1928021 TI - Opium addiction among Indochinese refugees in the United States: characteristics of addicts and their opium use. PMID- 1928020 TI - Relapse prevention strategies for the treatment of cocaine abuse. AB - A variety of promising pharmacotherapies, psychotherapies, and other treatments for cocaine abuse have recently been developed, many of which may facilitate the initiation of abstinence in cocaine abusers. This paper describes specific interventions and therapeutic strategies used in the treatment of cocaine abuse, adapted from Marlatt's theory of relapse prevention. These strategies extend Marlatt's primarily psychoeducational approach to address the unique difficulties presented in the treatment of cocaine abuse, which may include wide variations in patients' severity of abuse, available psychosocial resources, and coexistent psychopathology. This approach attempts to integrate relapse prevention techniques into a psychotherapeutic, rather than a purely psychoeducational approach, in order to enhance its effectiveness with cocaine abusers. PMID- 1928022 TI - Predictors of opiate drug abuse during a 90-day methadone detoxification. AB - The behavioral circumstances related to opiate drug use were examined during a 90 day out-patient methadone detoxification. Seventy-one subjects (55 male and 16 female) were followed from the day of intake to treatment termination. Data were collected by means of a weekly structured interview. Questions were asked about each occasion of opiate use in the previous week with respect to time, source, cost, social circumstance, etc. Monitored urine samples were tested x 3/week to verify verbal reports. The study demonstrated beneficial effects of the detoxification treatment by showing dramatic decreases in rates and amounts of opiate drug use during treatment. The study also identified race (p less than .0008; t = -3.522; beta = -0.366), gender (p less than .0243; t = 2.305; beta = 0.222), and the number of opiate use episodes/week at baseline (p less than .0013; t = -3.364; beta = -0.338) as significant and independent predictors of treatment outcome. Current duration of regular and continuous opiate use was also found to be marginally significant. The overall regression was highly significant (p less than .0001; F = 9.176; df = 4,66). A second regression analysis with race, age, and gender excluded as independent variables was conducted in order to derive indices which were related to behavioral and environmental characteristics versus global physical/cultural identification. With race and gender removed, the overall regression was still highly significant, although less than a fifth of the variance was accounted for. The number of opiate use episodes/week at baseline and the total number of drug-related stimulus cue exposures at baseline were found to be independently significant variables in the analysis. Knowledge of the impact of such behavioral factors on the treatment process may enable us to better understand the role of environmental contributors to opiate use. Such information may also help us to direct our limited resources and to better focus our treatment interventions. PMID- 1928023 TI - Dexamethasone suppression test in psychiatric patients with psychoactive substance dependence. AB - The study of the dexamethasone suppression test (DST) in 374 chronic psychiatric patients with concurrent substance dependence, including alcohol, found 97% of nonsuppression associated with affective disorders. The incidence of nonsuppression was 38.5% in major depressive disorder and 27.7% in bipolar affective disorder. This study found no apparent connection between the incidence of nonsuppression and any particular drug group. Predexamethasone plasma concentrations were higher in affective disorders than in other diagnoses. It is concluded that the DST may be of value as part of the clinical approach to the diagnosis of major depressive disorders in a substance-abusing population. PMID- 1928024 TI - Similar efficacy of abrupt and gradual opiate detoxification. AB - A study comparing abrupt and gradual opiate detoxification which identified the efficacy by means of computer-assisted pupilometry and rating of withdrawal distress is presented. This paper concentrates on the efficacies of these two detoxification modes with regard to the identical results after successful opiate detoxification treatment. The findings of the present investigation support the hypothesis that withdrawal distress returns to a normal level after rapid naloxone withdrawal treatment within 6 days. Similar results can be seen for inpatient methadone withdrawal after 3 weeks of treatment. These results indicate that by rapid detoxification therapy, the time of withdrawal can be effectively shortened. Considering the low dropout rate and the high degree of acceptance during rapid detoxification, the rapid detoxification regimen is an effective and economic alternative to gradual withdrawal treatments. PMID- 1928025 TI - Effect of drugs of abuse on psychiatric symptoms among hospitalized schizophrenics. AB - In a group of 71 inpatient schizophrenics with no other concurrent psychiatric diagnosis except for dependence on one drug, we ascertained the subjective effect their drug of abuse had on their psychiatric symptoms 2 weeks prior to hospitalization. Psychiatric symptoms were assessed by means of the Hopkins Symptom Checklist (Revised) (SCL-90R). Cocaine addicts, but not alcoholics, reported aggravation more often than improvement of symptoms. Alcoholics reported alcohol-induced symptom improvement with a similar frequency as alcohol-induced symptom aggravation. PMID- 1928026 TI - Substance abuse and schizophrenia: impediments to optimal care. AB - With lifetime prevalence estimates of substance abuse among schizophrenics as high as 47.01%, there is an increasing awareness of the importance of this dual diagnosis and the global deficiencies in our knowledge about this comorbid condition. Patients with substance abuse disorders and schizophrenia are problematic from a clinical, economic, and health care systems perspective. The lack of systematic research into phenomenology, etiology, and treatment approaches (both psychotherapeutic and psychopharmacologic) has hindered the development of an adequate strategy to care for the needs of these patients. Thus, these patients place a significant burden on the mental health delivery system through chronic disability, social dysfunction, frequent rehospitalizations, and poor overall treatment compliance. The authors critically review the contemporary literature relevant to concurrent substance abuse and schizophrenia, highlight major deficiencies in our knowledge, and call for research to reduce the individual, economic, and social costs of this condition. PMID- 1928027 TI - Intravenous drug users and AIDS: risk behaviors. AB - Risk-taking behaviors were studied in this assessment of 345 intravenous drug users from Baltimore, El Paso, and Denver. Over 50% reported injecting drugs daily and 70% shared needles with others, averaging 6.3 partners. In addition, 86% had shared a "cooker" and nearly 50% injected in a "shooting gallery." More than half of the males sampled had two or more sex partners, including 18% with five or more. Females averaged 19 sex partners in the preceding 6 months, with 22% reporting sex with five or more. Two-thirds of the total sample never used a condom, while only 6% always used this form of protection. On the other end of this risk continuum were those subjects who did not share needles or always cleaned their needles with an effective agent, had no sexual relations or always used a condom. Subjects following such practices could be considered low risk if they adopted safe behaviors in other associated areas of their lives. However, in an analysis of total risk, it was found that only 14 subjects (4%) practiced safe needle use and safe sex. Despite these findings, some encouraging results were seen. In an analysis of risk according to location, Baltimore subjects were significantly less at risk according to number of needle-sharing partners, borrowing needles, sharing a "cooker," injection in a "shooting gallery," cleaning needles, use of disinfectants, number of sexual partners, and use of condoms than either their cohorts in El Paso or Denver. Street outreach to modity risk behaviors among IVDUs began in Baltimore approximately 2 years prior to funding in El Paso and Denver. These results suggest that there may be a potential to moderate risk through intervention. PMID- 1928028 TI - Psychological reactions and retention by cocaine addicts during treatment according to HIV-serostatus: a matched-control study. AB - We compared retention in treatment and psychological reactions during drug abuse treatment by 22 HIV-antibody positive, physically asymptomatic cocaine addicts to 22 matched HIV-seronegative cocaine addicts. All subjects participated in an outpatient clinical research project. There were no significant differences between groups in sociodemographics and psychiatric symptom scores on entrance or cocaine use except for route of administration (chi 2 = 11.59, df = 2, p less than .005). There were no significant differences among groups regarding being informed of serostatus and beginning treatment. There was a trend (p = .079) for more seropositives to complete treatment. Using end-point analysis to compare 11 seropositive subjects who completed a minimum of 2 weeks of treatment to a matched seronegative comparison groups, there were no significant differences in mood states except for "anger/hostility" (interaction of group x time; F = 2.24, df = 13/260, p less than .05). Informing drug abusers in treatment regarding positive HIV-serostatus was not associated with a lower treatment-retention rate or adverse psychological reactions when counseling regarding HIV issues was integrated with drug abuse treatment. PMID- 1928029 TI - Assessment of severity in acute pancreatitis. AB - Assessment of severity of acute pancreatitis (AP) is a key determinant in the management of a patient. This review evaluates the various methods of assessment: clinical assessment, biochemical tests, Ranson's and Imrie's multiple prognostic criteria, simplified prognostic criteria, APACHE II, peritoneal lavage, and computed tomography. Although all of the above criteria can identify most of the seriously ill patients, each has some drawbacks. Individual preference and available institutional facilities greatly influence the method used for prognostic assessment in AP. However, some type of predictive assessment is possible in any hospital, and should be used in the management of patients with AP. PMID- 1928030 TI - Management of the pruritus of cholestasis: potential role of opiate antagonists. PMID- 1928031 TI - Histochemical pattern in alimentary tract duplications of children. AB - Detailed histological and histochemical studies using PAS, AB-PAS, and high-iron diamine-AB were done on 12 alimentary tract duplication cysts in children. Nine of these were thoracic and three were abdominal in location. A total of 11 cysts (nine thoracic and two abdominal cysts) were lined by gastric mucosa seen in varying stages of maturation. One triloculated cyst had, in addition, small intestinal mucosa and bronchial wall mucosa. One intra-mucosal rectal cyst was lined exclusively with primitive rectal mucosa. The cysts showed a variable pattern of mucin histochemistry. In three cysts, the gastric mucosa showed neutral mucins. In another three cysts, in addition to neutral mucins, focal positivity for sulphomucins was observed in the apical region of the surface epithelial cells. In the remaining five cysts, the gastric mucosa showed neutral mucins along with a variable mixture of sulpho- and sialomucins. A correlation was seen between mucin histochemistry and the age of the patient. Neutral mucins or focal positivity for sulphomucins was seen in patients aged 7 months or more, whereas a mixture of sulpho-, sialo-, and neutral mucins was identified in patients who were 1 month old, or less. PMID- 1928032 TI - Gastric cell proliferation kinetics and bile reflux after partial gastrectomy. AB - Thirty-four randomized, partially gastrectomized subjects (12 with a Billroth II, 11 with a Billroth I, and 11 with a total biliary diversion reconstruction) were studied in order to assess the relationships between bile reflux, gastric histology, and cell proliferation kinetics. Bile acid quantity and concentration in the gastric aspirates progressively decreased from Billroth II to Billroth I to total biliary diversion (after which reflux was almost absent). Perianastomotic mucosa in Billroth II subjects showed the greatest degree of foveolar hyperplasia, and this decreased markedly with increasing distance from the anastomosis. Hyperplastic changes were less evident in Billroth I, and virtually absent in total biliary diversion subjects. The overall foveolar hyperplasia-like behavior of cell kinetic parameters (total pit cell number, labeled pit cell number, and labeling index) was shown. Moreover, subjects with mean bile acid concentration greater than 150 mumol/L had both a greater prevalence of foveolar hyperplasia and greater values of cell kinetic parameters than those with mean bile acid concentration less than or equal to 150 mumol/L. A superficialization of the proliferative compartment was also evident in the former group. These results show a close relationship between postgastrectomy bile reflux, foveolar hyperplasia, and cell kinetic parameters. Histologic and cell kinetic findings are probably the expression of gastric adaptation to chronic bile reflux exposure. Moreover, the type and entity of cell kinetic involvement and its relationship to foveolar hyperplasia and reflux may suggest new "tools" in post-gastrectomy surveillance and help to clarify patterns of gastric carcinogenesis. PMID- 1928033 TI - Influence of physical activity on gastric emptying of liquids in normal human subjects. AB - Liquid gastric emptying has been evaluated in 17 normal human subjects during basal conditions, after mild physical stress at 50% of the maximum predictable heart rate, and after maximal physical stress at 70% maximum heart rate. Each subject exercised on a treadmill for 30 min, its speed and inclination varied in order to obtain the desired heart rate. Immediately after the exercise, 400 ml of mineral water were drunk by each subject. Gastric emptying was evaluated by real time ultrasonography (11 subjects) and scintigraphy (six subjects) through previously described methods. The results show similar data with both techniques. Gastric emptying of the water, considered either as reduction in gastric measurements at ultrasonography or decay in radioactivity in the region of interest corresponding to the stomach at scintigraphy, follows a linear relationship under basal conditions and during physical stress. Compared with basal conditions, gastric emptying of water after maximal stress was prolonged; after mild stress, gastric emptying of the water was accelerated. These findings may support the common belief that mild physical activity favors the digestive process. PMID- 1928034 TI - A comparative study of contrast agents for endoscopic retrograde pancreatography. AB - Pancreatitis is a major cause of morbidity and mortality secondary to endoscopic retrograde pancreatography (ERP). One factor that may cause post-ERP pancreatitis is the type of contrast media utilized during the procedure. The purpose of this prospective, double-blind, randomized study was to evaluate the effects of three contrast agents of differing osmolality and ionicity on changes between pre- and post-ERP chemical changes in serum amylase and lipase and development of clinical symptoms of acute pancreatitis. Our study of 53 patients showed that those who received Omnipaque a non-ionic, relatively iso-osmolar contrast agent, had a significantly lower serum amylase (p = 0.0038) and serum lipase (p = 0.0002) in post-ERP serological markers, compared with patients who received the ionic agents, Hypaque meglumine 60% or Hexabrix. In addition, the development of clinical symptoms of pancreatitis was less in patients who received Omnipaque than in those who received Hexabrix or Hypaque (1 vs. 3 vs. 4). No significant difference was found between patients who received ionic agents. No patient who received Omnipaque needed hospitalization, whereas one (6%) patient who received Hexabrix was hospitalized compared to three (20%) hospitalized patients who received Hypaque. When the initial cost and cost of hospitalization were compared, the non-ionic contrast medium was also found to be more cost-effective for the patient. In summary, the risk of post-ERP acute pancreatitis was significantly lower for patients who received the non-ionic contrast agent than for those who received the ionic agents. PMID- 1928035 TI - Use of HemoQuant assays to assess the effect of oral iron preparations on stool hemoccult tests. AB - To determine whether oral iron preparations taken in therapeutic doses are capable of causing either true-positive, false-positive, or false-negative fecal occult blood Hemoccult tests, a prospective, before/after trial was conducted in the gastroenterology clinic of an Army medical center. Fourteen healthy volunteers were studied in four 1-wk periods, during which a single stool sample was collected on the 3rd, 5th, and 7th days for Hemoccult testing and HemoQuant assay. No iron preparations were ingested during the 1st and 3rd wk, and these results served as control values. One 324-mg tablet of ferrous sulfate was ingested orally three times each day during the 2nd wk and one 324-mg tablet of ferrous gluconate was ingested three times each day during the 4th wk of the study. All 84 stool specimens collected during the 2 wk of oral iron therapy were negative on Hemoccult testing, and the results of corresponding quantitative assays for fecal blood by the HemoQuant method were normal and did not differ significantly from control values. The Hemoccult test results from our study differ markedly from those of a previous study of similar design using only Hemoccult tests and oral iron preparations. Also, our HemoQuant data confirmed that oral iron preparations, in therapeutic doses, do not interfere with HemoQuant assay. Ferrous sulfate and ferrous gluconate tablets ingested in therapeutic doses do not cause false-positive, true-positive, or false-negative stool Hemoccult tests and do not cause a significant increase in gastrointestinal blood loss compared to controls as assessed by the Hemo-Quant assay. Any positive stool Hemoccult test detected in individuals ingesting therapeutic doses of oral iron preparations should not be regarded as a false-positive test. PMID- 1928036 TI - Comparison of different measurements of intestinal permeability in inflammatory bowel disease. AB - We have compared different measurements of small intestinal permeability in 28 patients with Crohn's disease affecting the small intestine, 14 with ulcerative colitis and 17 controls. Patients and controls were given a drink containing 100 microCi (3.7 MBq) of 51Cr-ethylene diamine tetraacetic acid (51Cr-EDTA), 5 g lactulose, 5 g cellobiose, 1 g rhamnose, and 2 g mannitol. Urine was collected to 6 h after dosing, and then from 6 until 24 h. Recoveries of 51Cr-EDTA, lactulose, rhamnose, and mannitol were expressed as percentages of the amount administered. The only measurement that distinguished patients with Crohn's disease from both controls and patients with ulcerative colitis was the recovery of 51Cr-EDTA in the first 6 h after dosing. The mean recovery in patients with Crohn's disease was 1.07%; in controls, it was 0.35% (p = 0.013); in ulcerative colitis it was 0.39% (p = 0.032 compared to Crohn's; p = 0.492 compared to controls). No other measurement of permeability differentiated the three groups. Recoveries of 51Cr EDTa and lactulose were highly correlated in each of the three groups. Recovery of rhamnose was significantly correlated with that of mannitol. In the patients with Crohn's disease, recovery of 51Cr-EDTA to 6 h was significantly correlated with some nonspecific laboratory indicators of inflammatory activity, namely, erythrocyte sedimentation rate, platelet count, white blood cell count, serum albumin, and C-reactive protein, but not with hemoglobin. PMID- 1928037 TI - The chemotactic response of human granulocytes to Clostridium difficile toxin A is age dependent. AB - Elderly patients are at high risk for developing diarrhea and colitis as a complication of antimicrobial therapy. Clostridium difficile, the causative agent of antibiotic-associated diarrhea and colitis produces an enterotoxin (toxin A) and a cytotoxin (toxin B). Of these two exotoxins, toxin A appears to be largely responsible for the inflammatory phenomena of C. difficile colitis, because it produces secretion, pronounced granulocytic infiltration, and epithelial cell necrosis and ulceration in ligated ileal loops of experimental animals. We have recently demonstrated that the inflammatory effects of C. difficile toxin A in the intestine may be related to its ability to mobilize intracellular calcium and elicit a chemotactic response by human granulocytes. In this study, in order to explain why the elderly are at greater risk for developing antibiotic-associated colitis, we investigated the effects of toxin A on activation of granulocytes from healthy elderly and young subjects. Highly purified toxin A and the chemotactic factor N-formyl-Met-Leu-Phe (FMLP) at concentrations of 10(-7) M both elicited a significant (p less than 0.001) and comparable chemotactic and chemokinetic response in human granulocytes from both age groups. A significantly (p less than 0.001) increased chemotactic effect in elderly subjects compared with young subjects was elicited by toxin A and not by FMLP. These findings suggest that the enhanced intestinal inflammatory effects of C. difficile in the elderly, compared with the young, may be related to the ability of its enterotoxin to elicit a more pronounced chemotactic response by granulocytes. PMID- 1928038 TI - Diverticulitis: an evaluation by computed tomography and contrast enema. AB - The role of a contrast enema and computed tomography (CT) was evaluated in 228 patients with a discharge diagnosis of acute diverticulitis. Forty-nine percent of these patients eventually required surgery. In the surgical group, 90% of contrast enemas and 69% of CT examinations reported either diverticulitis or findings compatible with diverticulitis. In patients treated medically, the negative results were higher with both modalities, although it is believed that a number of these patients were misdiagnosed. The contrast enema and CT influenced the decision for surgery in 17% and 6%, respectively, in patients undergoing these examinations. PMID- 1928039 TI - Pseudo-obstruction associated with colonic ischemia: successful management with colonoscopic decompression. AB - Colonic pseudo-obstruction has been associated with colonic ischemia in only 7 10% of cases. When both conditions are present, most authors recommend immediate laparotomy because of the additional weakening of the bowel wall induced by the presence of ischemia and the resultant increased risk of perforation. We report on three patients with pseudo-obstruction and right-sided colonic ischemia who were successfully managed with colonoscopic decompression with tube placement. Surgery may not be required in patients with pseudo-obstruction and associated colonic ischemia. PMID- 1928040 TI - Single-parameter DNA flow cytometric analysis of normal-appearing colonic mucosa does not predict the presence of colonic neoplasia. AB - We wished to determine whether DNA flow cytometric analysis could detect DNA abnormalities in normal-appearing mucosa of patients with colonic neoplasia. Eighty-five patients were studied either at colonoscopy or at surgical resection. Forty-five had macroscopically normal colonoscopy; 13 had adenomatous polyps, and 27 had colorectal carcinoma. Biopsies were obtained from the cancer and from normal-appearing mucosa 5 cm from the lesion. The patients who had normal colonoscopy had rectal biopsies. The samples were prepared for analysis on a Coulter EPICS C flow cytometer. Cells were analyzed for presence of aneuploidy (%AN), percent in DNA synthetic phase (%S), and percent growth fraction (%GF = %S + %G2M). Aneuploidy was present in 12 of 27 carcinomas (44%), but in none of the samples from polyps or normal-appearing colorectal mucosa adjacent to cancers. The %S from cancers was greater than those from polyps (9.6 +/- 6.3 vs. 5.1 +/- 1.8, p less than 0.005). However, %S from specimens arising from normal-appearing mucosa 5 cm distant from cancer could not be differentiated from the rectal mucosa of macroscopically normal colons (5.9 +/- 2.5 vs. 5.2 +/- 2.7). The %GF of cancer specimens was greater than those from adenomas (26.0 +/- 11.0 vs. 10.8 +/- 3.7, p less than 0.005). However, the %GF of normal-appearing mucosa 5 cm distant from the cancer was similar to the findings from mucosa arising from macroscopically normal colons (10.5 +/- 3.3 vs. 11.0 +/- 3.4). In conclusion, DNA flow cytometric analysis of normal-appearing colonic mucosa from patients with colonic carcinoma does not demonstrate abnormalities of DNA content or cell cycle kinetics, and therefore, cannot predict the presence of colonic neoplasia. PMID- 1928041 TI - The sentinel hyperplastic polyp: a marker for synchronous neoplasia in the proximal colon. AB - We prospectively screened 129 asymptomatic subjects (mean age 64 yr) with flexible sigmoidoscopy. Colonoscopy was performed at a later date, regardless of the sigmoidoscopic result. Our intent was 1) to establish the prevalence of proximal neoplasms in patients with and without hyperplastic polyps within reach of the 60-cm sigmoidoscope and 2) to determine whether a distal (sentinel) hyperplastic polyp predicts the presence of synchronous neoplastic polyps higher up in the colon. Our results show that 15% of asymptomatic adult subjects without polyps on sigmoidoscopy have adenomas in proximal colonic segments that can be diagnosed only by colonoscopy. By comparison, proximal neoplasms were detected in 32% (p less than 0.05) and 37% (p less than 0.05) of patients when hyperplastic or adenomatous polyps, respectively, were present on the sigmoidoscopic examination. This finding suggests that a distal (sentinel) hyperplastic polyp by itself may be a marker for neoplastic polyps in proximal colonic segments. Also, the "index" adenoma and "sentinel" hyperplastic polyp may be equivalent for predicting the presence of proximal neoplasms. The observed detection rates for these polyps were both significantly higher than expected when compared to patients who did not have polyps in the distal colon or rectum. If these results can be confirmed by a larger prospective trial, then full colonoscopy for detection of proximal neoplasms may be indicated when either an index adenoma or sentinel hyperplastic polyp is detected by sigmoidoscopy. PMID- 1928042 TI - Cholecystectomy and colorectal carcinoma: a total-population historical prospective study. AB - The relationship between cholecystectomy and colorectal cancer in the Icelandic population was analyzed in a historical prospective study. A total of 3,425 individuals (857 males and 2,568 females) who underwent cholecystectomy during a 26-yr period (1955-1980) were followed for 8-33 yr. The risk of colonic cancer in Icelandic males increased significantly 11 yr or more after operation (relative risk, 2.73; 95% confidence interval, 1.25-5.19). This is the only study that shows a significantly increased risk of colonic cancer in males only. In spite of this increased risk, regular screening for colonic cancer in Icelandic males would probably not be warranted, since almost 70% of the males are 70 yr old or older at the time of diagnosis. PMID- 1928043 TI - Breast cancer-associated protein pS2 expression in tumors of the biliary tract. AB - Expression of pS2 (an estrogen-induced gene isolated from breast carcinoma MCF7 cells) and of the human spasmolytic peptide (hSP) gene was analyzed in 21 human biliary tract and gallbladder carcinomas and 16 non-neoplastic gallbladders at the protein level (immunochemistry) and, in a series of these cases, at the RNA level (Northern blots). Eighteen carcinomas and 14 non-neoplastic mucosae with inflammatory alterations showed pS2 activity by immunostaining or Northern blotting. In addition, in samples with pS2 expression, hSP RNA was demonstrated. In the corresponding non-neoplastic and healthy mucosae, pS2 was negative, as judged by immunostaining. Northern blots showed weak (basal) level of activity for pS2 and hSP. The genes' increased expression in correlation to inflammatory and neoplastic processes, by now observed in several carcinomas and idiopathic inflammatory bowel disease, hints to their essential role in such diseases. PMID- 1928044 TI - Anti-hepatitis C antibodies in patients with chronic non-A, non-B hepatitis: relation to disease progression and effect of interferon alpha. AB - The activity of antibodies to hepatitis C virus (anti-HCV) was investigated in 80 patients with chronic non-A, non-B liver diseases. Serum anti-HCV titer was determined by the "Ortho-HCV" enzyme-linked immunosorbent assay with some modifications to quantify the activity. Anti-HCV was positive in 82.5% of cases (66/80). Anti-HCV occurred significantly less often in the patients with chronic persistent hepatitis (8/13, 61.5%) than in those with chronic active hepatitis (42/49, 85.7%) (p less than 0.05). Anti-HCV titer of the patients with chronic persistent hepatitis and that with chronic active hepatitis was significantly higher than that with liver cirrhosis (p less than 0.01 and p less than 0.05). There was no correlation between anti-HCV titer and histology activity index in chronic hepatitis. Serial study demonstrated that anti-HCV titer decreased more frequently in the patients who responded to IFN alpha therapy (11/22, 50.0%) than in those who did not respond to IFN alpha therapy (0/10, 0%) (p less than 0.01). These results indicate that anti-HCV level does not correlate with the activity of hepatitis, but that it decreases in accordance with the disease progression to liver cirrhosis or with the response to IFN alpha therapy. PMID- 1928045 TI - Ascites adenosine deaminase activity is decreased in tuberculous ascites with low protein content. AB - The value of adenosine deaminase activity (ADA) in ascitic fluid was examined in 12 patients with confirmed peritoneal tuberculosis and compared with that of 96 patients with ascites of other different etiologies as an age-matched control group, to determine the diagnostic value of the ADA activity in tuberculous ascites. The mean adenosine deaminase activity (ADA) value in ascitic fluid of the tuberculous peritonitis group was 47.9 +/- 21.9 IU/L and in the control group 9.6 +/- 5 U/L (mean +/- SD); p less than 0.01. A different method than that usually reported in tuberculous peritonitis was used for ascites ADA estimation. The best sensitivity and specificity was obtained when greater than 32 U/L was used as a cutoff point. The ascites ADA activity correlated with the ascites total protein concentration in the tuberculosis group (r = 0.842). Our findings confirm other results and support the ADA activity determination in ascitic fluid as a useful noninvasive screening test in the diagnosis of peritoneal tuberculosis in endemic areas or in high risk patients. However, false-negative results may occur in those patients in which ascites total protein concentration is low. PMID- 1928046 TI - Low serum T3 and raised reverse T3 levels in hepatic cirrhosis: role of glucagon. AB - Hepatic parenchymal tissue is known to be one of the major sites of thyroid hormone metabolism as well as glucagon action. Alterations in circulating thyroid hormone concentrations, as well as hyperglucagonemia, are well documented in subjects with hepatic cirrhosis and advanced liver dysfunction. Also, we have documented recently that hyperglucagonemia induced in normal subjects alters thyroid hormone metabolism, with lowering of serum T3 and a rise in serum reverse T3 (rT3) levels. Thus, it is conceivable that rising glucagon concentrations are responsible for altered thyroid hormone levels in hepatic cirrhosis. To examine this hypothesis, this study determined relationships between plasma glucose, glucagon, insulin, and insulin:glucagon ratio on one hand, and thyroid hormone concentrations on the other, in 51 subjects with hepatic cirrhosis. Significant negative correlations were noted between plasma glucagon and serum T3 (r = 0.418, p less than 0.001) as well as T3:T4 ratio (r = -0.627, p less than 0.0001), whereas significant positive correlations were observed between plasma glucagon and serum rT3 (r = 0.504, p less than 0.001) as well as rT3:T4 ratio (r = 0.644, p less than 0.0001). No such significant relationships were noted between either insulin, glucose and insulin:glucagon ratio on one hand and any of thyroid hormone indices on the other. Therefore, this study indicates that, in hepatic cirrhosis, circulating glucagon concentrations may play a major contributing role in induction of altered serum thyroid hormone concentration by influencing thyroid hormone metabolism. PMID- 1928048 TI - Diabetic gustatory sweating. AB - Gustatory sweating is an unusual entity that may occur as an idiosyncratic reaction to certain foods, as a localized reaction to trauma or infection, or as the result of diabetic neuropathy. This report deals with a severe case of diabetic gustatory sweating, discusses the various types of gustatory sweating, and reviews the English literature dealing with the diabetic form. PMID- 1928047 TI - Prognostic indicators in compensated cirrhosis. AB - In an attempt to identify variables predicting prognosis, 100 consecutive patients with compensated cirrhosis of the liver were followed for a mean of 4.9 (SD 0.7) yr. Fifty-one patients belonged to Child-Pugh class A, 49 to class B. At entry, five laboratory parameters were considered, together with sex, the grade of esophageal varices, and seven variables measured by ultrasonography (liver and spleen volume and the calibers of the splanchnic vessels). In a subgroup of 56 patients, the galactose elimination capacity also was determined. Forty-six patients were alive at the end of follow-up. Survival was analyzed according to Cox's model. Six parameters were able to predict survival (albumin, bilirubin, liver volume, prothrombin activity, cholesterol, varices). However, step-wise Cox regression analysis identified only four variables that independently correlated with survival: albumin, bilirubin, cholesterol, and liver volume. Galactose elimination failed to add any significance to routine liver function tests. This prospective study confirms the ability of routine liver function tests in predicting survival in compensated cirrhosis. The measurement of liver volume, easily obtained by ultrasonography, is also significant for prognosis, and may be introduced into clinical practice. PMID- 1928049 TI - Epidermolysis bullosa acquisita (EBA) and esophageal webs: a new association. AB - Epidermolysis bullosa acquisita (EBA) is a well-defined, blistering disorder of the skin associated with autoantibodies to type VII collagen. Although esophageal pathology is common in children with hereditary dystrophic forms of epidermolysis bullosa, esophageal problems have not been reported previously in patients with bona fide EBA. In this report, a 71-yr-old white female with longstanding EBA presented with recurrent dysphagia and multiple esophageal webs that responded to esophageal dilatation. PMID- 1928050 TI - Intrahepatic biliary papillomatosis arising in nonobstructive intrahepatic biliary dilatations confined to the hepatic left lobe. AB - Papillomatosis of intrahepatic bile ducts is a rare pathologic entity. We describe herein a case of papillomatosis of intrahepatic bile ducts associated with nonobstructive dilatations of intrahepatic bile ducts of the hepatic left lobe. The patient, a 70-yr-old female, complained of right upper abdominal pain. Cholangiograms revealed multiple cystic dilatations of the left intrahepatic bile ducts. The right intrahepatic bile ducts were almost normal. The patient underwent left lobectomy of the liver. Grossly, intrahepatic bile ducts of the left lobe were cystically dilated and contained a little mucinous fluid. The inner surface of the dilated ducts was mildly granular or papillary. Microscopically, the walls of the dilated intrahepatic ducts were diffusely covered by columnar epithelial cells with papillary configurations. There was mild atypia of the epithelial cells, but no invasion of the epithelial cells into underlying duct walls was found. To the best of our knowledge, this is the first case of papillomatosis of intrahepatic bile ducts associated with nonobstructive dilatations of intrahepatic bile ducts confined to the left lobe. Although the pathogenesis of intrahepatic biliary papillomatosis of our case is unclear, it seems conceivable that biliary irritation associated with the nonobstructive dilatations of intrahepatic bile ducts is causally related to the papillary proliferations of intrahepatic bile duct epithelial cells. PMID- 1928051 TI - Biliary obstruction secondary to shrapnel. AB - Foreign bodies of the biliary tree represent infrequent causes of obstructive jaundice. We report a patient who developed biliary obstruction from metal shrapnel, 44 yr after a war injury. From our review of the literature, the syndrome of shrapnel-induced obstructive jaundice may occur many years after the initial injury. In the majority of patients, the missile lodges in the liver parenchyma, and migrates to the common bile duct. Complications from this injury include cholangitis, pancreatitis, and liver abscesses. As demonstrated by this case, computed tomography scan and endoscopic retrograde cholangio-pancreatogram may reliably detect this infrequent occurrence. With the development of therapeutic biliary procedures, many foreign bodies can be removed endoscopically. Thus, one should consider shrapnel-induced biliary obstruction in those patients with obstructive jaundice and prior combat injury. PMID- 1928052 TI - Phlegmonous enteritis in alcoholic fatty liver. AB - Phlegmonous enteritis is a rare inflammatory bowel disease. A 52-yr-old man with a history of alcoholic abuse was admitted to the hospital for an acute abdomen and died of septicemia and its complications. Autopsy revealed phlegmonous inflammation of the ileum and severe fatty liver. Numerous Gram-negative rod bacilli were demonstrated in the ileal mucosa. Shortened villi and decreased lysozyme activity of Paneth cells in the small intestine might be results of chronic alcohol ingestion. The relationship between phlegmonous enteritis and alcoholic abuse was strongly suggested in this case. PMID- 1928053 TI - Acute colonic pseudo-obstruction associated with interleukin-2 therapy. AB - In this case report, we present a patient with metastatic gastric carcinoma who developed massive colonic dilatation during treatment with recombinant interleukin-2. The spectrum of gastrointestinal symptomatology associated with interleukin-2 therapy is broad. However, colonic pseudo-obstruction, to our knowledge, has never before been reported. We review therapy for colonic pseudo obstruction and a proposed mechanism of interleukin-2 toxicity. We report this case to heighten awareness of the potential for the development of this complication in patients undergoing interleukin-2 immunotherapy. PMID- 1928054 TI - Disappearance of a sessile tubulovillous adenoma in the rectosigmoid colon during radiation therapy for cervical carcinoma. AB - Colonoscopic polypectomy is the usual treatment for an adenomatous colorectal polyp. We report a case of a sessile tubulovillous adenoma in the rectosigmoid colon disappearing during a course of radiation therapy for an unrelated cervical cancer. This case report illustrates that at least some colonic polyps are radiosensitive and can be eradicated during radiation therapy. PMID- 1928055 TI - Massive rectal bleeding from a Dieulafoy's type ulcer of the rectum: a review of this unusual disease. AB - Dieulafoy's ulcer is an uncommon lesion that usually presents with massive bleeding. Although it has been observed, for the most part, in the stomach, it has also been identified in the small bowel and colon. Both endoscopy and angiography have been used for diagnosis; however, endoscopy has had a high failure rate for localizing colonic disease during active bleeding. Treatment has been primarily surgical, but endoscopic coagulation and sclerotherapy have been recently employed. A 20-year-old male presented with massive lower gastrointestinal bleeding, which was found to be caused by a Dieulafoy's ulcer in the rectum. Observation of Dieulafoy's ulcer in the rectum has not been reported previously. Diagnosis was by rigid sigmoidoscopy. This lesion was treated by widely oversewing the vessel after endoscopic therapy failed. The etiology of this lesion is most likely congenital. Hemorrhage probably occurs as a result of mechanical damage of the mucosa, combined with erosion of the vessel by fecal flow. Unlike colonic Dieulafoy's ulcers, it should be possible to diagnose rectal lesions by rigid sigmoidoscopy. This diagnosis may be difficult with high rectal ulcers, and angiography may have to be employed. Endoscopic therapy failed here, as in other reports on colonic disease. Thus, we would recommend widely oversewing rectal lesions as the primary treatment. Resection should be reserved for cases that have failed this therapy. PMID- 1928057 TI - Chronic diarrhea in the acquired immunodeficiency syndrome: evidence for another opportunist. PMID- 1928056 TI - Noncardiac chest pain: conundrum of cause and effect. PMID- 1928058 TI - Treatment of diversion colitis with 5-aminosalicylic acid enemas: comparison with betamethasone enemas. PMID- 1928059 TI - Occurrence of hemothorax (unilateral) after sclerotherapy. PMID- 1928060 TI - Chronic active hepatitis in alcoholics. PMID- 1928061 TI - Extrarenal potassium tolerance in chronic renal failure: implications for the treatment of acute hyperkalemia. AB - The role of extrarenal potassium homeostasis is well recognized as a major mechanism for the acute defense against the development of hyperkalemia. The purpose of this report is to examine whether or not the various mechanisms of extrarenal potassium regulation are intact in patients with end-stage renal disease (ESRD). The available data suggest that with the development of ESRD and the uremic syndrome there is impaired extrarenal potassium metabolism that is related to a defect in the Na,K-adenosine triphosphatase (ATPase). The responsiveness of uremic patients to the various effector systems that regulate extrarenal potassium handling is discussed. Insulin is well positioned to play an important role in the regulation of plasma potassium concentration in patients with impaired renal function. The role of basal insulin may be even more important than previously appreciated, since somatostatin infusion causes a much greater increase in the fasting plasma potassium in rats with renal failure than in controls. Furthermore, stimulation of endogenous insulin by oral glucose results in a greater intracellular translocation of potassium in uremic rats than in controls. Under at least two common physiologic circumstances, feeding and vigorous exercise, endogenous catecholamines might also act to defend against acute increments in extracellular potassium concentration. However, it is important to appreciate that the response to beta 2-adrenoreceptor-mediated internal potassium disposal is heterogeneous as judged by the variable responses to epinephrine infusion. Based on the evidence presented in this report, a regimen for the treatment of life-threatening hyperkalemia is outlined. Interpretation of the available data demonstrate that bicarbonate should not be relied on as the sole initial treatment for severe hyperkalemia, since the magnitude of the effect of bicarbonate on potassium is variable and may be delayed. The initial treatment for life-threatening hyperkalemia should always include insulin plus glucose, as the hypokalemic response to insulin is both prompt and predictable. Combined treatment with beta 2-agonists and insulin is also effective and may help prevent insulin-induced hypoglycemia. PMID- 1928063 TI - Use of low-dose subcutaneous recombinant human erythropoietin in end-stage renal disease: experience with children receiving continuous cycling peritoneal dialysis. AB - The use of recombinant human erythropoietin (rhEPO) for the treatment of renal anemia is well accepted. However, the lowest effective dose for subcutaneous (SC) administration has not been determined. This study documents that a dose of 50 U/kg administered three times a week was effective in 10 children (age range, 13 days to 18.6 years) receiving continuous cycling peritoneal dialysis (CCPD) for a period ranging from 0.25 to 23.5 months. Their hematocrit (hct) increased at an average rate of 0.26% points per day from a baseline of 19.8% +/- 3.1% to a value of at least 30% after a mean of 7.4 +/- 2.5 weeks of treatment. When compared with other studies, this response was more rapid than what has been observed with the same dose administered intravenously (IV). This response was similar to that seen with larger IV doses. Hypertension and functional iron deficiency were the most common complications. Two patients with previously controlled hypertension developed elevation in blood pressure that was easily controlled by oral antihypertensives. Six patients required IV iron dextran to reestablish treatment response. A SC rhEPO dose less than 50 U/kg three times a week may be effective in children and should be investigated. PMID- 1928062 TI - Plasma oxalate in patients with chronic renal failure receiving continuous ambulatory peritoneal dialysis or hemodialysis. AB - Plasma oxalate was measured in 20 patients receiving continuous ambulatory peritoneal dialysis (CAPD) and 20 patients receiving hemodialysis (HD). All patients had levels well above the reference range of less than 2.0 to 5.0 mumol/L (less than 0.18 to 0.44 mg/L), the medians being 34 mumol/L (2.99 mg/L) and 42 mumol/L (3.70 mg/L) for the two groups, respectively. Plasma oxalate did not differ significantly in the two groups. Plasma oxalate was not influenced by the number of months patients had received dialysis treatment, but a significant correlation was found between oxalate and creatinine in the 40 patients studied (P less than 0.02, r = 0.38). Predialysis oxalate levels were reduced by approximately 60% following HD, but returned to 80% of the predialysis levels within 24 hours and 95% within 48 hours. Oxalate levels did not differ significantly in samples taken before, during, and after exchanges of CAPD fluid. That the patients treated with CAPD did not have higher oxalate levels than the HD group suggests that the continuous nature of the former treatment compensates for the lower oxalate clearance by the peritoneum. The reported higher risk of oxalosis associated with intermittent peritoneal dialysis has led to a similar risk being postulated for CAPD; however, the present study indicates that if such a risk exists, it cannot be explained by higher levels of oxalate or ionized calcium in these patients. PMID- 1928064 TI - Continuous venovenous hemofiltration: an alternative to continuous arteriovenous hemofiltration and hemodiafiltration in acute renal failure. AB - Continuous venovenous hemofiltration (CVVH) has been used as an alternative to continuous arteriovenous hemofiltration (CAVH) and hemodiafiltration (CAVHD) in the management of critically ill patients with acute renal failure. This report describes our experience with the first 25 patients treated with CVVH at our institution. Vascular access was obtained through a single dual-lumen venous catheter. A blood pump was used to provide ultrafiltration pressure. An ultrafiltrate pump was incorporated to ensure predictable ultrafiltrate production rates. Safety features in the extracorporeal circuit included a venous drip chamber with bubble detector and an in-line pressure monitor. CVVH was initiated by a nephrologist and dialysis nurse and was maintained by the intensive care unit (ICU) nursing staff. Fifteen females and 10 males received CVVH therapy for a total of 193.5 days (average, 7.7 +/- 10.3 days; range, 0.5 to 48 days). Four of the 25 patients (16%) survived and were discharged from the hospital. Four additional patients (16%) survived the acute phase of their illness, but died from complications of their primary disease before discharge from the hospital. The mean weight change during CVVH was -7.9 +/- 7.0 kg (range, -26.5 to +2.9 kg). Metabolic waste products and electrolytes were adequately controlled by CVVH in all but one hypercatabolic patient. The mean heparin dose required was 6.5 +/- 4.2 U/kg/h and was adjusted to prevent filter clotting rather than to achieve a predetermined activated partial thromboplastin time (PTT). The median PTT was 35.8 seconds (range, 22.0 to 100; control, 19.5 to 29.5 seconds). Four episodes of volume-responsive hypotension occurred during the 193.5 treatment days. Only one patient experienced a hemorrhagic complication during CVVH. No patient experienced a complication related to vascular access. Twelve of 111 total hemofilters were changed because of clot formation. CVVH was well tolerated by patients and managed efficiently by the ICU nursing staff.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928065 TI - C1q nephropathy: a pediatric clinicopathologic study. AB - We report on 15 children with proteinuria, at the nephrotic level in the majority of cases, who had no histologic glomerular alterations (eight cases), or focal and segmental glomerular scarring with (three cases) or without (four cases) mesangial proliferation. In all cases, immunofluorescence (IF) microscopy showed prominent mesangial C1q deposits with variable amounts of immunoglobulins. Ultrastructurally, most had conspicuous mesangial electron-dense deposits. Cases with no glomerular histologic alterations were histologically indistinguishable from minimal change disease (MCD), yet they uniformly had an unsatisfactory response to oral prednisone. Thus, the presence of immune deposits with a prominent C1q contribution identifies a group of cases that respond poorly to steroids and that, if light microscopy is considered in isolation, might otherwise be designated MCD. PMID- 1928066 TI - Serum IgA-fibronectin aggregates in patients with IgA nephropathy and Henoch Schonlein purpura: diagnostic value and pathogenic implications. The Glomerular Disease Collaborative Network. AB - IgA nephropathy is a common form of glomerulonephritis that has varied clinical expressions, ranging from asymptomatic hematuria to rapidly progressive nephritis. We report the strong association (P less than 0.0001) of circulating IgA-fibronectin aggregates with IgA nephropathy. Of 30 patients with IgA nephropathy, 93.3% had serum IgA-fibronectin aggregates detected with an enzyme immunoassay using collagen as a substrate to bind the aggregates. Among the patients with IgA-fibronectin aggregates were patients with Henoch-Schonlein purpura and recurrent crescentic IgA nephropathy in transplants. Only 11.7% of 103 patients with other types of glomerular disease and 6.7% of normal controls had positive IgA-fibronectin aggregate assay levels. IgA-fibronectin aggregates also were detected in serum using an antifibronectin antibody capture assay; and could be depleted from serum by heparin-agarose affinity chromatography. The circulating IgA-fibronectin aggregates had the same unusual predominance of lambda relative to kappa light chains that is observed in the glomerular deposits of IgA nephropathy. The data indicate that IgA-fibronectin aggregates are a useful serologic marker for IgA nephropathy, Henoch-Schonlein purpura, and recurrent IgA nephropathy in transplants. The presence of fibronectin in the circulating aggregates may play an important role in the preferential deposition of nephritogenic IgA-containing immune complexes in the mesangium of patients with IgA nephropathy. PMID- 1928067 TI - Urinary porphyrin excretion in normal children and adults. AB - The relationship of random urinary porphyrin and creatinine values as functions of age and sex was examined in a normal population. Total urinary porphyrin was measured by a solvent extraction technique, while urinary creatinine was evaluated by an alkaline picrate method. Random urine specimens from 120 healthy patients (81 children and 39 adults) were evaluated. In both pediatric and adult populations, a strong correlation was found between urinary concentrations of porphyrin and creatinine (r = 0.7, P less than 0.0001). Urinary porphyrin excretion in mumol/mol creatinine (micrograms/g) was inversely related to both age (r = -0.59, P less than 0.0001) and weight (r = -0.61, P less than 0.0001) until approximately 9 years of age or 30 kg. Urinary porphyrin excretion in children 9 to 18 years of age was lower than that of younger children (P less than 0.0001) and approached adult values. Sex was not found to be a factor until 9 to 18 years of age, when females had higher urinary creatinine concentrations (P less than 0.05), but lower urinary porphyrin excretions (P less than 0.05) than similarly aged males. The converse was observed when similar values of adult women were compared with those of adult men. Men also had higher urinary porphyrin concentrations than women (P less than 0.01). Men had increased urinary creatinine concentration (P less than 0.05) and decreased porphyrin excretion ratios (P less than 0.05) when compared with males 9 to 18 years of age. Women had significantly lower urinary creatinine (P less than 0.001) and porphyrin (P less than 0.001) concentrations than females 9 to 18 years of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928068 TI - Familial renal adysplasia. AB - Renal dysplasia and agenesis as isolated findings are usually considered sporadic, noninherited abnormalities. We report three kindreds with familial renal adysplasia. Two or more children were affected in each of the families and at least one member--whether proband, sibling, or parent--had a clinically silent anomaly. Normal kidneys in the parents did not preclude the occurrence of renal adysplasia in more than one child. The empiric risks for offspring and first degree relatives were 50% and 25%, respectively, suggesting a strong genetic factor such as a major dominant gene with variable expression. Because the disease appears to be genetic in some cases of renal adysplasia, careful screening of the proband's family, subsequent children, and pregnancies is important for the purpose of accurate genetic counseling. PMID- 1928069 TI - The multicystic kidney and hereditary renal adysplasia. PMID- 1928070 TI - Adenovirus infection of the kidney: mass formation in a patient with Hodgkin's disease. AB - Adenovirus (AV) infection usually has a benign course in normal hosts; however, in immunocompromised patients, AV may cause pneumonia, cystitis, or disseminated disease with substantial morbidity and even mortality. Although pulmonic AV involvement is common, infection of the kidney is unusual. The histologic findings previously described include tubular necrosis with interstitial inflammation and glomerulonephritis. We report a case of an AV-induced unilateral mass lesion in the kidney of a patient with Hodgkin's disease (HD) following bone marrow transplantation. PMID- 1928071 TI - Long-term follow-up of a human subject with a remnant kidney. AB - It has been proposed that once functioning renal mass has been reduced below a critical level, either as the result of disease, congenital absence of a kidney, or surgical ablation, that hyperfiltration and glomerular hypertension lead to progressive glomerular sclerosis and end-stage renal failure. We report the clinical course and renal function of a human subject followed for 10.8 years after extensive renal ablation. Functioning renal mass was estimated at one fourth to one fifth of normal. During the follow-up period, creatinine clearance increased from 0.27 mL/s (16 mL/min) to 0.88 mL/s (53 mL/min), the total renal plasma flow (all of which was to the left kidney) increased from 62 mL/min to 190 mL/min, and 24-hour urine protein excretion increased from 0.09 g to 0.4 g. Despite probable glomerular hyperfiltration, neither progressive glomerular dysfunction nor end-stage renal failure developed over a period of 10 years. PMID- 1928072 TI - Membranous nephropathy developing in a patient with previously diagnosed focal glomerulosclerosis. PMID- 1928073 TI - From protein to gene to protein: the molecular biology of erythropoietin. PMID- 1928074 TI - Erythropoietin: sites of synthesis and regulation of secretion. AB - Erythropoietin (Epo) is a glycoprotein that promotes the proliferation and differentiation of erythrocyte precursors. The major site of Epo production is the kidney, while the liver is the main extrarenal site of Epo production. Within these organs, the cells synthesizing Epo were identified by using in situ hybridization in hypoxic animals with an increased Epo mRNA expression. Epo producing cells in the kidney were peritubular cells, most likely endothelial cells of the cortex and outer medulla. Glomerular and tubular cells were not labeled. In three patients with renal adenocarcinomas associated with polycythemia, in situ hybridization showed a strong labeling of the tumor cells. Epo secretion is stimulated by hypoxia, which is detected by an oxygen sensor located in the kidney. This oxygen sensor has been recently shown to be an heme protein. At the Epo gene level, studies to identify cis-acting DNA sequences, and trans-activation factors for inducible kidney and liver Epo expression are being pursued. PMID- 1928075 TI - National cooperative rHu erythropoietin study in patients with chronic renal failure: a phase IV multicenter study. Report of National Cooperative rHu Erythropoietin Study Group. AB - Initial experience with recombinant human erythropoietin (rHuEPO, epoetin alfa) was gained through research protocols in which patient selection and management were tightly controlled. When epoetin alfa was approved for use by the Food and Drug Administration (FDA) these constraints were removed. The present study was designed to examine the medical and social impact of epoetin alfa therapy, as well as to document its safety and efficacy as it is used in clinical practice. From 1,000 to 2,000 patients at 100 to 200 centers will be enrolled and monitored for 1 year. Two groups of patients are being studied--those already receiving epoetin alfa at study entry and those new to epoetin alfa therapy. Demographic data are collected initially and detailed outcome data are collected monthly. This interim report presents data from 68 participating dialysis centers on 447 enrolled patients. To date, 89% of the patients are on in-center hemodialysis, while 9% are on home dialysis (79% continuous ambulatory peritoneal dialysis [CAPD], 14% continuous cyclic peritoneal dialysis [CCPD]). Preliminary analyses suggest this population is similar in age and cause of chronic renal failure to the overall US dialysis population, although whites and males are somewhat underrepresented. Of those already on epoetin alfa at study entry, 62% were receiving 3,000 to 9,000 U/wk. In addition, those already on epoetin alfa had better self-rated general health than those new to therapy. Outcomes and epoetin alfa usage patterns are currently being fully analyzed. Three-month follow-up data on a cohort of patients new to epoetin alfa indicate that the average dose in these patients is less than 100 U/kg/wk; two thirds of the doses were administered intravenously. Hematocrit levels increased over the 3 months from a level of 25.1% at entry to 30.6% by month 3. The percentage of cohort patients who were transfusion-independent increased from 85.1% at study entry to 95.7% by month 3. No increases in the incidence of adverse events occurred in the cohort group and no changes in the safety profile were indicated. These preliminary findings suggest that low doses of rHuEPO are being used in general, with a resultant low mean hematocrit. Thus, patients do not seem to be realizing the full potential beneficial effects of this remarkable agent. PMID- 1928076 TI - Erythropoietin 1991--an overview. AB - Recombinant human erythropoietin (epoetin) is a remarkably safe and effective biological product. Many dialysis patients are benefiting from the use of this drug when administered intravenously (IV) or subcutaneously (SC) three times a week. However, many patients are not receiving optimal therapy. Optimal therapy requires an understanding of the principles of effective usage and a definition of an optimal hematocrit (Hct) level. These therapeutic principles include (1) the erythroid response to epoetin is dose-dependent, but variable within a given dose; (2) the SC route of injection is as effective, if not more so, than IV injections; (3) the frequency of administration is route-dependent; (4) adequate iron stores are necessary for optimal response; (5) blood pressure may increase as the Hct increases, but may improve with time due to hemodynamic adjustments; (6) the anemia is primarily a hormone-deficiency state and not due to uremia; and (7) infections and traumatic (ie, surgical) inflammation may blunt the response to epoetin. Many patients with the anemia of renal failure have yet to benefit from treatment. These include patients with progressive renal failure or chronic transplant rejection, and dialysis patients who have had incomplete correction of their anemia. PMID- 1928077 TI - Recombinant human erythropoietin in predialysis patients. AB - This report reviews the author's experience and the results of a multicenter study with regard to the use of recombinant human erythropoietin (Epo) in predialysis patients. The data demonstrate that Epo corrects anemia and improves quality-of-life assessment and exercise capacity in patients who are not dialyzed, but who have renal insufficiency. The incidence of hypertension was 22% in the Epo-treated subjects and 19% in the placebo group. Within the Epo-treated group, there appears to be a greater frequency of hypertensive events in those subjects receiving the higher dosages. The concern that Epo might accelerate the deterioration of renal function is not substantiated by several clinical studies. PMID- 1928078 TI - Erythropoietin use in peritoneal dialysis patients. AB - Erythropoietin (Epo) is currently used less extensively in peritoneal dialysis (PD) patients than in hemodialysis (HD) patients. Early data suggest that Epo is equally effective in PD patients, and that the risk profile is similar. No adverse consequences to the dialysis procedure or peritonitis rates have been consistently noted. It has been suggested that PD patients may require less Epo than their HD counterparts, but this is unproven. Further research on the preferred route of administration and timing of the dosing is necessary. PMID- 1928079 TI - Pediatric uses of recombinant human erythropoietin: the outlook in 1991. AB - Extensive clinical studies have documented the effectiveness of recombinant human erythropoietin (rHuEPO) in correcting the anemia of adult dialysis patients, but the safety and efficacy of rHuEPO in children with renal anemia cannot yet be confirmed, due to the relative deficiency of reported studies involving pediatric subjects. To date, published experience with rHuEPO therapy in children has totaled 257 patients, although the majority of these reports have appeared only as abstracts. Overall experience has been favorable, with renal anemia and transfusion dependency successfully resolved in almost all pediatric patients reported. However, controlled clinical trials have not been performed, so it is not yet possible to clearly define the risks associated with rHuEPO therapy in children. Hypertension appears to occur or become worse in up to one third of treated children, but it is unclear to what extent rHuEPO therapy is accompanied by an increased risk of seizures, thrombosis of vascular access, hyperkalemia, hyperphosphatemia, or peritonitis (when administered via the intraperitoneal route). Only preliminary and somewhat conjectural recommendations can be offered regarding pediatric rHuEPO dosing, route of administration, special precautions, and adjunctive monitoring and therapy. Fortunately, a multicenter controlled clinical trial is underway that is designed to address these issues. Because the harmful effects of renal anemia are typically more profound for children than they are for adults, the benefits of rHuEPO promise to be even greater among pediatric patients. Whether rHuEPO therapy will substantially improve growth and neurologic and psychosocial development remains to be seen, but the potential is there for rHuEPO to dramatically improve the lives of children who suffer from the effects of the anemia of chronic renal failure. Other non-renal anemias that afflict pediatric patients, such as the anemia of prematurity, also may be amenable to rHuEPO therapy. PMID- 1928080 TI - Interrelationship between erythropoietin and erythropoiesis: insights from renal transplantation. AB - In successful renal transplant recipients, transient and modest increases in endogenous erythropoietin (Epo) reverse anemia, whereas in dialysis patients, sustained administration of large doses of exogenous Epo is required for the correction of uremic anemia. Moreover, in transplant recipients, serum Epo returns to normal as the hematocrit level increases to greater than 32%. Thereafter, the hematocrit continues to increase to normal levels, while serum Epo remains in the normal range. Thus, the restoration of renal function may improve the erythropoietic response to Epo, and/or erythropoiesis in transplant patients may be stimulated by factors other than, or in addition to, Epo. In early posttransplant patients who develop erythrocytosis, serum Epo levels are often elevated, while in long-term transplant recipients, erythrocytotic patients (with normal serum ferritin) have normal serum Epo levels. On the other hand, in long-term transplant recipients with low serum ferritin, circulating Epo levels are elevated, even in patients with no overt anemia. This suggests a possible interaction between body iron store status and the synthesis of Epo. PMID- 1928081 TI - The impact of recombinant human erythropoietin therapy on renal transplantation. AB - This report describes the potential and actual effects that recombinant human erythropoietin (rHuEpo) may have on the practice of renal transplantation. Three aspects are highlighted. The first is the effects in the dialysis patient transplanted after treatment with rHuEpo. These include the potential risks of graft thrombosis and prolonged initial nonfunction (for which there is little supportive evidence), and the impact on pretransplant immune-modulating regimens, which take advantage of the so-called transfusion effect. As the importance of this effect to overall graft survival has diminished strikingly, this may be of little consequence. The second aspect relates to the highly presensitized dialysis patient. The literature and our own data are presented, showing the beneficial effects of rHuEpo therapy on reducing the level of humoral anti-HLA sensitization. This may lead to benefits that include reduced time on the waiting list for a cadaveric renal transplant, and possibly improved allograft survival. Finally, our data on the use of rHuEpo in 13 patients with anemia (usually due to chronic graft failure) after transplantation is discussed. rHuEpo therapy was effective in all patients, leading to reversal of anemia. Side effects, including hypertension and hypertensive seizures, occurred in the subgroup of patients with significant renal dysfunction (serum creatinine greater than 2.5 mg/DL). PMID- 1928082 TI - Recombinant human erythropoietin and the quality of life of end-stage renal disease patients: a comparative analysis. AB - The clinical and quality of life outcomes of hemodialysis patients improve remarkably following treatment with recombinant human erythropoietin (Epo). However, few studies have compared the quality of life of Epo patients with that of end-stage renal disease (ESRD) patients on various treatment modalities. Data obtained in three separate studies of ESRD patients were comparatively analyzed. Over 1,500 patients from 23 dialysis and transplant centers were studied. Both objective and subjective quality of life were examined. Objective quality of life indicators included employment status, functional ability, and health status. Subjective quality of life indicators included well-being, life satisfaction, psychological affect, and happiness. Quality of life varied significantly across treatment modality, with transplant recipients generally reporting the highest levels of objective and subjective quality of life. However, hemodialysis patients treated with Epo reported a statistically significant improvement between baseline and 10 months' follow-up on all quality of life indicators, except employment. Epo patients reported a level of overall life satisfaction that exceeded that of patients on all ESRD treatment modalities. Among transplant recipients, diabetics reported the poorest quality of life, while patients on conventional immunosuppressive therapy often had a quality of life that exceeded that of patients on cyclosporine therapy. Some of these findings may be explained by case-mix differences, as well as differing study designs. Quality of life remains a significant concern among ESRD patients and the physicians and medical professionals responsible for their care. Unfortunately, the rehabilitation potential of many patients, despite the availability of Epo, and the success of transplantation, remains unmet. PMID- 1928083 TI - Impact of erythropoietin on the dialysis prescription. AB - Close on the heals of the first successful reports of recombinant human erythropoietin (rHuEPO) use in dialysis-associated anemia, concern surfaced that raising the hematocrit level could threaten both the safety and efficacy of hemodialysis. Theoretical considerations prompted the conclusion that by decreasing the plasma water space available for dialysis, removal of plasma solutes would decrease in direct proportion to the increase in hematocrit. Predictions of thrombotic disaster were also aired, citing the increase in blood viscosity expected after correction of anemia. After 18 months of widespread use of rHuEPO in the United States, clinical experience has shown that correction of anemia can be accomplished without serious impact on either safety or efficacy in both conventional and high efficiency/high dialysis. Although predialysis concentrations of creatinine, phosphate, and potassium may increase whenever the hematocrit increases substantially, the magnitude of the rise is limited. Increased predialysis solute concentrations, which may be caused by either decreased dialyzer efficiency or increased dietary intake due to improved appetite, are readily managed by increasing dialysis blood flow rate, dialyzer surface area, and dialysis time. Since these measures may have little effect on increased phosphate levels, increased administration of phosphate binders may be required. However, by way of caution, the ready dialyzability of urea renders the predialysis blood urea nitrogen (BUN), as well as urea kinetics, relatively unaffected by the change in hematocrit, thereby masking adverse effects on other solutes. Fortunately, serious thrombotic consequences have not been seen, probably because anticoagulation is adequately managed by routine increases in heparin utilization. PMID- 1928084 TI - Effects of erythropoietin on blood pressure. AB - Increased blood pressure (BP) has been the most commonly reported side effect in trials of treatment of the anemia of chronic renal failure with recombinant human erythropoietin (rHuEPO). An increase in BP develops in one third of patients, in most cases necessitating initiation or increase of antihypertensive therapy. Elevated BP is not related to dose of rHuEPO, nor to the final hematocrit level achieved or the rate of increase of hematocrit. Increases in BP arise particularly during the first 4 months of therapy, and BP usually stabilizes thereafter. rHuEPO therapy does not appear to affect BP in patients with normal renal function. The mechanism of hypertension related to rHuEPO remains uncertain. An increase in systemic vascular resistance occurs in all patients, whether or not BP increases. This is due largely to increased blood viscosity and reversal of hypoxic vasodilatation, but other factors may also contribute. A lack of adequate reduction in cardiac output distinguishes patients in whom BP increases, and this in turn may be due to abnormal cardiovascular autoregulation in these patients. Acute elevation in BP during rHuEPO therapy occasionally results in hypertensive encephalopathy and seizures. This complication is unrelated to the extent or rate of increase in hematocrit, but is associated with a rapid increase in BP, and may occur in previously normotensive patients. Hypertension developing during rHuEPO therapy should be controlled by conventional antihypertensive therapy. If hypertension persists, the rHuEPO dose should be reduced or therapy temporarily discontinued. Frequent BP monitoring during the first 4 months of treatment is mandatory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928085 TI - Side effects of erythropoietin therapy. AB - Recombinant erythropoietin is usually associated with marked improvement in physiological and psychological well-being. Adverse effects are unusual. In this report, the unusual occurrence of seizures, increased clotting, and influenza like syndromes is reviewed. Emphasis is given to adverse effects noted in the few available placebo-controlled studies. PMID- 1928087 TI - Medicare payment options for recombinant erythropoietin therapy. AB - We analyzed alternative payment approaches that Medicare could use to pay for recombinant human erythropoietin (rHuEPO) therapy. How Medicare pays for rHuEPO therapy will affect whether providers make prudent purchases of the biologic and prescribe it appropriately and whether companies offer the program low prices. Medicare's policies may also guide policies of other third parties. Selecting payment options for Medicare payment requires balancing desirable and undesirable implications, especially trade-offs between improving access to and quality of care for beneficiaries versus constraining costs to Medicare and its beneficiaries. The options for paying providers that contain financial incentives to constrain expenditures also contain incentives for providers to skimp on use, perhaps to the detriment of patients' quality of care. On the other hand, options that may reward additional use may lead to higher expenditures and threaten the quality of care from the direction of overuse. Medicare currently varies the level and method of payment for rHuEPO therapy according to the setting in which it is provided. Equity among beneficiaries and providers and incentives for efficient use of medical services would argue for paying the same amount for the same service, regardless of where it was provided. Whatever payment options are adopted, the Health Care Financing Administration (HCFA) will have to be able to exercise flexibility in monitoring and responding to changing market conditions. In this dynamic market, the number of manufacturers, medical indications for use approved by the Food and Drug Administration, and, eventually, Medicare's predominance are likely to evolve over time. The appropriate level and perhaps even the method of payment may well change with market conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928086 TI - Modulating factors in the hematopoietic response to erythropoietin. AB - The absence of any response to the administration of recombinant human erythropoietin (rHuEpo) is exceptional in uremic patients with anemia. Initial "nonresponders" generally respond to higher doses of the hormone. However, a small number of patients may remain unresponsive. The most common cause of limited response is mild to moderate iron deficiency, either at the start of treatment or secondary to enhanced iron utilization by newly formed erythrocytes. Another common cause of resistance is the presence of an overt or, more often, an unrecognized inflammatory state, including acute or chronic infection. Marked aluminum overload and severe hyperparathyroidism also have been shown to induce resistance in at least some patients. Other factors may contribute to the severity of anemia and hence increase rHuEpo requirements, such as acute or chronic hemolytic conditions or blood loss, folate deficiency, hemoglobinopathies, and still poorly defined uremic toxins. In patients who show a resistance to the effect of the recombinant hormone, these should be sought and eliminated, if possible. PMID- 1928088 TI - Recombinant human erythropoietin therapy in the surgical setting and applications in oncology. AB - The development of recombinant human erythropoietin (Epo), along with a sensitive and reproducible assay for plasma Epo, has resulted in new potential applications for the treatment of medical and surgical anemias. A series of studies have defined a role for Epo therapy in the perisurgical setting to include the facilitation of autologous blood procurement and to facilitate postoperative erythropoiesis in order to minimize homologous blood transfusion requirements. Other possible applications of Epo therapy include the treatment of medical illnesses. Clinical trials to date have demonstrated that Epo therapy can correct the anemias of renal insufficiency, of rheumatoid arthritis, and of acquired immunodeficiency syndrome (AIDS) patients undergoing antiviral therapy. Clinical trials investigating the application of Epo therapy in the oncologic setting are in progress. These developments herald a new age in transfusion medicine, which includes the use of pharmacologic therapies in blood conservation strategies. PMID- 1928089 TI - Expressed hypervariable polymorphism of apolipoprotein (a). AB - Elevated plasma lipoprotein (a) (LP(a] levels are an independent predictor of the development of premature atherosclerosis in humans. The LP(a) particle consists of two disulfide-linked proteins, apolipoprotein (APO) B and APO(a). The APO(a) is a highly glycosylated protein which carries the LP(a) antigen. Genetic polymorphism in the APO(a) molecule has been reported, and, depending on the sensitivity of the method used, 6-11 alleles at the APO(a) structural locus have been documented in the literature. In this investigation, we have used a high resolution SDS-agarose electrophoresis method followed by immunoblotting to screen APO(a) polymorphism in 54 families with 130 offspring. This method identified a total of 23 different APO(a) isoforms, and their genetic basis was confirmed in families. In addition to the detectable products of 23 APO(a) alleles, the family data predict the existence of a "null" allele. Of the total 270 individuals tested, 209 (77.4%) revealed double-banded phenotypes and 61 (22.6%) revealed single-banded phenotypes. In the unrelated sample of 140 individuals, however, 114 (81.4%) and 26 (18.6%) had double- and single-banded phenotypes, respectively. When the segregation pattern of single-banded phenotypes in the unrelated sample was followed in families, only nine (6.4%) were found to be true homozygotes, and the remaining 17 (12.2%) were classified as heterozygotes for the null allele. Of the 276 possible phenotypes predicted for 23 alleles in a large population, we observed 115 (42%) phenotypes in our restricted sample. On the basis of our results from the family data, we hypothesize the existence of at least 24 alleles, including a null allele, at the APO(a) structural locus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928090 TI - Identification of a splice-site mutation in the aldolase B gene from an individual with hereditary fructose intolerance. AB - Hereditary fructose intolerance (HFI) is a potentially fatal autosomal recessive disease of carbohydrate metabolism. HFI patients exhibit a deficiency of fructose 1-phosphate aldolase (aldolase B), the isozyme expressed in tissues that metabolize fructose. The eight protein-coding exons, including splicing signals, of the aldolase B gene from one HFI patient were amplified by PCR. Dot-blot hybridization of the amplified DNA with allele-specific oligonucleotide (ASO) probes revealed a previously described A149P mutation in one allele from the proband. The mutation in the other allele was identified by direct sequencing of the double-stranded PCR-amplified material from the proband. The nucleotide sequence of exon 9 revealed a 7-base deletion/1-base insertion (delta 7 + 1) at the 3' splice site of intron 8 in one allele. This mutation was confirmed by cloning PCR-amplified exon 9 of the proband and determining the sequence of each allele separately. ASO analysis of 18 family members confirmed the Mendelian inheritance of both mutant alleles. The implications of this unique splice-site mutation in HFI are discussed. PMID- 1928092 TI - Human beta-galactosidase gene mutations in morquio B disease. AB - Three different beta-galactosidase gene mutations--a 273Trp----Leu (mutation F) in both families, 482Arg----His (mutation G) in one family, and 509Trp----Cys (mutation H) in the other family--were identified in three patients with Morquio B disease who were from two unrelated families. Restriction-site analysis using StuI, Nsp(7524)I or RsaI confirmed these mutations. In human fibroblasts, mutation F expressed as much as 8% of the normal allele's enzyme activity, but the other mutations expressed no detectable enzyme activity. We conclude that the unique clinical manifestations are specifically associated with mutation F, a common two-base substitution, in this disease. PMID- 1928091 TI - Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His----Tyr): complete structure of the normal human CA II gene. AB - Carbonic anhydrase II (CA II), which has the highest turnover number and widest tissue distribution of any of the seven CA isozymes known in humans, is absent from the red blood cells and probably from other tissues of patients with CA II deficiency syndrome. We have sequenced the CA II gene in a patient from a consanguinous marriage in a Belgian family and identified the mutation that is probably the cause of the CA II deficiency in that family. The change is a C-to-T transition which results in the substitution of Tyr (TAT) for His (CAT) at position 107. This histidine is invariant in all amniotic CA isozymes sequenced to date, as well as the CAs from elasmobranch and algal sources and in a viral CA related protein. His-107 appears to have a stabilizing function in the structure of all CA molecules, and its substitution by Tyr apparently disrupts the critical hydrogen bonding of His-107 to two other similarly invariant residues, Glu-117 and Tyr-194, resulting in an unstable CA II molecule. We have also completed the intron-exon structure of the normal human CA II gene, which has allowed us to prepare PCR primers for all exons. These primers will facilitate the determination of the mutations in other inherited CA II deficiencies. PMID- 1928093 TI - Risk calculation in retinitis pigmentosa. PMID- 1928094 TI - Eugenics: past, present, and the future. AB - During the past 20 years there has been a resurgence of interest in the history of the eugenics movements, particularly those of the United States and Germany. Unfortunately, most of these accounts have been published in nonmedical and nongenetic journals, so they are not readily available to geneticists or physicians. The authors of this article are concerned about the lack of information that geneticists, physicians, and students have concerning the origin and progress of these movements. This article provides a short history of the American and German eugenics programs and concludes with a review of their possible relations to our current practices. It is hoped that this will encourage institutions to include, in master's Ph.D., and M.D. programs in human genetics, lectures, seminars, and journal clubs on the topic of eugenics. PMID- 1928095 TI - Using medical genetics applications to educate for computer competence. AB - This article proposes specific areas of computing competence and illustrates how these skills can be acquired as an integral part of the curriculum of medical genetics. Geneticists are at the forefront in the use of computers for medical care, because of the driving force of the Human Genome Project. Computer searching of international data bases is the most efficient method to keep current with the explosion in molecular genetics data and with its immediate relevance to clinical care. The use of computers in genetics education could go far beyond the use of computer-assisted instruction (CAI) to show how to use computer systems to assist with clinical decisions. The proposed basic computer skills can be obtained using genetics software. The six proposed skills include the use of (1) microcomputers, (2) productivity software, (3) CAI, patient simulations and specific application programs, (4) remote computers, (5) data bases and knowledge bases, and (6) computers to improve the clinical care of patients. PMID- 1928096 TI - American Society of Human Genetics presidential address, October 18, 1990. PMID- 1928097 TI - Nonuniform linkage disequilibrium within a 1,500-kb region of the human immunoglobulin heavy-chain complex. AB - We have characterized 10 VH polymorphic loci of the VH2, VH3, VH4, and VH5 families. Eight of 10 VH polymorphisms were found to be insertion/deletion polymorphisms, probably the result of nonhomologous recombination over the course of evolution of the current human VH repertoire. The 10 VH polymorphic loci were analyzed in 10 three-generation and 10 two-generation Canadian caucasoid families. Linkage disequilibrium (allelic association) was measured between pairs of VH polymorphic loci, and 12 significant associations were found. The degree of linkage disequilibrium measured between IGH polymorphic loci was then compared with the physical distance separating the loci. The physical distance between IGH polymorphic loci does not entirely determine the degree of linkage disequilibrium between polymorphic loci. Two regions, one in the VH region (between VH3f-2 and VH5-2 and one in the CH region (between C delta and C gamma 3), were found to have linkage disequilibrium values approximately 1/3,000 of that observed in other portions of the IGH region. The previous identification of recombinants in the C delta-to C gamma 3 region indicates that these areas of low linkage disequilibrium are consistent with the presence of recombination hot spots. The observed high amount of recombination in the subtelomeric portion of chromosome 14 therefore appears to be the result of specific hot spots for recombination, rather than a general increase in recombination in this region. PMID- 1928098 TI - Complex segregation analysis of autism. AB - A complex segregation analysis of autism in 185 Utah families was carried out using the mixed model. The 209 affected individuals in these families represent nearly complete ascertainment of the autistic cases born in Utah between 1965 and 1984. The sibling recurrence risk for autism was 4.5% (95% confidence limits 2.8% 6.2%). Likelihoods were maximized for major-gene models, a polygenic model, a sibling-effect model, and a mixed model consisting of major-gene and shared sibling effects. The analysis provided no evidence for major-locus inheritance of autism. Subdivision of the sample according to the probands' IQ levels showed that sibling recurrence risk did not vary consistently with IQ level. A segregation analysis of families in which the proband had an IQ less than 50 also failed to provide evidence for a major locus. However, because of the etiologic heterogeneity of this disorder, genetic analysis of other meaningful subsets of families could prove informative. PMID- 1928100 TI - Carrier detection and prenatal diagnosis in Duchenne and Becker muscular dystrophy families, using dinucleotide repeat polymorphisms. AB - To improve carrier detection and prenatal diagnosis for Duchenne and Becker muscular dystrophy families, we determined allele frequencies and measures of variation for four (dC-dA)n.(dG-dT)n loci identified within a deletion-prone region of the human dystrophin gene. The loci are highly polymorphic, with predicted heterozygosities of 71.6%-93.3%. Direct DNA sequence analysis of the (dC-dA)n.(dG-dT)n locus in intron 49 revealed an additional length polymorphism which varies by single-basepair increments, is adjacent to the dinucleotide repeat block, and enhances the polymorphic content of this marker. The four (dC dA)n.(dG-dT)n loci are each easily amplified by PCR in two diplex reactions. The variability of allele lengths at these loci makes them ideal for carrier detection and prenatal diagnosis, often providing diagnostic information when RFLP analysis is uninformative. These markers have aided in identification of deletion mutations, exclusion of maternal cell contamination of chorionic villus samples, confirmation of paternity, and mapping of gene recombinations. The allele identification of these loci can be performed either with a radiolabel or with an automated, nonradioactive, fluorescent gel detection system. PMID- 1928099 TI - Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. AB - Biochemical and molecular genetic evidence is presented that in six independent pedigrees the development of Leber hereditary optic neuropathy (LHON) is due to the same primary mutation in the mitochondrial ND1 gene. A LHON family from the Newcastle area of Great Britain was analyzed in depth to determine the mitochondrial genetic etiology of their disease. Biochemical assays of mitochondrial electron transport in organelles isolated from the platelet/white blood-cell fraction have established that the members of this family have a substantial and specific lowering of flux through complex I (NADH-ubiquinone oxidoreductase). To determine the site of the primary mitochondrial gene mutation in this pedigree, all seven mitochondrial complex I genes were sequenced, in their entirety, from two family members. The primary mutation was identified as a homoplasmic transition at nucleotide 3460, which results in the substitution of threonine for alanine at position 52 of the ND1 protein. This residue occurs within a very highly conserved hydrophilic loop, is invariantly alanine or glycine in all ND1 proteins, and is adjacent to an invariant aspartic acid residue. This is only the second instance in which both a biochemical abnormality and a mitochondrial gene mutation have been identified in an LHON pedigree. The sequence analysis of the ND81 gene was extended to a further 11, unrelated LHON pedigrees that had been screened previously and found not to carry the mitochondrial ND4/R340H mutation. The ND1/A52T mutation at nucleotide 3460 was found in five of these 11 pedigrees. In contrast, this sequence change was not found in any of the 47 non-LHON controls. The possible role of secondary complex I mutations in the etiology of LHON is also addressed in these studies. PMID- 1928101 TI - D19S51 is closely linked with and maps distal to the myotonic dystrophy locus on 19q. AB - Recent genetic linkage studies have mapped the myotonic dystrophy (DM) locus to 19q13.3. All closely linked DM markers identified to date have been located on the centromeric side of the disease locus, with a relatively large genetic interval (9 cM) observed between the nearest distal marker and DM. We show here that the recently described marker p134C is tightly linked to DM (peak lod score 35.8 at peak recombination fraction .006) and confirm the previous suggestion that the p134C locus, D19S51 maps distal to the disease locus. D19S51 and the closest proximal flanking loci, ERCC1 and D19S115 (pE0.8), define a small genetic interval of less than 2 cM that contains the DM locus. PMID- 1928102 TI - Linkage disequilibrium between two highly polymorphic microsatellites. AB - The PCR was used to amplify genomic DNA from two microsatellite (dC-dA)n.(dG-dT)n sequences found to be present in the same chromosome 5 genomic clone. Analysis of the haplotype frequencies of these two interspersed repeat sequences in individuals showed strong allelic association or linkage disequilibrium. Six alleles were found for p599 (CA)n with a PIC value of 0.71 and 8 alleles were seen for lambda 599 (CA)n with a PIC value of 0.74. The two microsatellites are separated by approximately 7 kb. Analysis of the length variations for the two microsatellites showed that they were positively correlated, a finding that has no obvious explanation. The strong linkage disequilibrium found demonstrates stability during evolution for these novel markers. Therefore they should be powerful new tools for studying genetic drift and admixture of populations. Furthermore, disequilibrium data from microsatellites can be used in the fine mapping and cloning of disease genes. PMID- 1928103 TI - Tight linkage of the gene for spinocerebellar ataxia to D6S89 on the short arm of chromosome 6 in a kindred for which close linkage to both HLA and F13A1 is excluded. AB - A locus for an autosomal dominant form of spinocerebellar ataxia (SCA1) has been assigned to the short arm of chromosome 6 on the basis of linkage to the major histocompatibility system (HLA). In this study of a five-generation American black family, close linkage between the disease locus and both HLA and the coagulation factor XIIIA (F13A1) locus was excluded, and lod scores for all locations of the disease locus between HLA and F13A1 were less than -1.4. These results suggest that the locus causing spinocerebellar ataxia in this family is not in this region. However, the disease locus was found to be closely linked to a microsatellite polymorphism, D6S89, which is between HLA and F13A1. The maximum lod score for SCA1 and D6S89 is 4.90 at a recombination fraction of 0, both in males and in females. These data show that exclusion of close linkage to the HLA complex and F13A1 in a kindred with spinocerebellar ataxia does not rule out the possibility that the disease locus in that family is on 6p. Accordingly, all families segregating a dominantly inherited ataxia should be evaluated for linkage to D6S89, to determine whether the locus causing the disease is SCA1. PMID- 1928104 TI - Influence of aberrant observations on high-resolution linkage analysis outcomes. AB - Because of the availability of efficient, user-friendly computer analysis programs, the construction of multilocus human genetic maps has become commonplace. At the level of resolution at which most of these maps have been developed, the methods have proved to be robust. This may not be true in the construction of high-resolution linkage maps (3-cM interlocus resolution or less). High-resolution meiotic maps, by definition, have a low probability of recombination occurring in an interval. As such, even low frequencies of errors in typing (1.5% or less) may influence mapping outcomes. To investigate the influence of aberrant observations on high-resolution maps, a Monte Carlo simulation analysis of multipoint linkage data was performed. Introduction of error was observed to reduce power to discriminate orders, dramatically inflate map length, and provide significant support for incorrect over correct orders. These results appear to be due to the misclassification of nonrecombinant gametes as multiple recombinants. Chi 2-Like goodness-of-fit analysis appears to be quite sensitive to the appearance of misclassified gametes, providing a simple test for aberrant data sets. Multiple pairwise likelihood analysis appears to be less sensitive than does multipoint analysis and may serve as a check for map validity. PMID- 1928105 TI - De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints. AB - A questionnaire sent to major cytogenetics laboratories in the United States and Canada over a 10-year period collected data on the frequency and outcome of cases with either apparently balanced de novo rearrangements or de novo supernumerary marker chromosomes detected at amniocentesis. Of 377,357 reported amniocenteses, approximately 1/2,000 had a de novo reciprocal translocation, 1/9,000 a Robertsonian translocation, 1/10,000 a de novo inversion, and 1/2,500 an extra structurally abnormal chromosome of unidentifiable origin. The risk of a serious congenital anomaly was estimated to be 6.1% (n = 163) for de novo reciprocal translocations, 3.7% (n = 51) for Robertsonian translocations, and 9.4% (n = 32) for inversions. The combined risk for reciprocal translocations and inversions was 6.7% (95% confidence limits 3.1%-10.3%). The risk of abnormality for extra nonsatellited marker chromosomes was 14.7% (n = 68), and that for satellited marker chromosomes was 10.9% (n = 55). In non-Robertsonian rearrangements, distribution of breakpoints among chromosomes was not as would be expected strictly on the basis of length. Most breaks were stated to occur within G negative bands, but there was little evidence of particular hot spots among these bands. Nevertheless, there did appear to be a correlation between those bands in which breakage was observed most often and those bands where common or rare fragile sites have been described. PMID- 1928106 TI - Mortality of employed men and women in England and Wales. PMID- 1928107 TI - Mortality of employed men and women. AB - This paper presents mortality data for a 1% sample of men and women in England and Wales who were employed at the time of the 1971 Census of Population. It provides background information on the "healthy worker effect" by age, social class (as determined by occupation), cause of death, and length of follow-up. As expected, relative mortality of those employed at census rose with subsequent follow-up. This effect was strongly age-related, apparently as a consequence of the development (and increasing predominance) of chronic diseases with age. This suggests a unified explanation for some of the variation described in the literature. Statistical modelling of the relationship between mortality and length of follow-up confirmed that the healthy worker effect did not entirely disappear as follow-up progressed in this study. We examined social background as an explanation for this persistently low mortality, but found no evidence to suggest that it was an important factor. PMID- 1928108 TI - A longitudinal study of pulmonary function in fire fighters. AB - Pulmonary function changes among fire fighters were evaluated by re-examining 632 Baltimore city fire fighters six to ten years after a baseline examination. Spirometry was used to determine forced expiratory volume in 1 second (FEV1). Information about exposures was obtained by questionnaire and by combining data from fire department records regarding the number of fires fought by fire fighting units with individual work histories. Men who never wore a mask while extinguishing fires experienced a 1.7 times greater rate of FEV1 decline than mask wearers. Men with ammonia exposure experienced a rate of decline 1.7 times greater than non-exposed men. Neither length of time spent in exposed jobs nor number of responses were associated with the rate of decline. Active fire fighters experienced a rate of decline 2.5 times greater than those who had retired or resigned. Some effects differed between men who were able to perform repeatable pulmonary function tests and those who were not. PMID- 1928109 TI - An industry-wide epidemiologic study of vinyl chloride workers, 1942-1982. AB - The cohort consisted of 10,173 men who had worked for at least one year in jobs involving exposure to vinyl chloride prior to 1 January 1973. These men were employed at 37 plants in the U.S., belonging to 17 companies. Observation of the mortality experience of the cohort was updated from 31 December 1972 to 31 December 1982 (the study now covering 1942-1982). A total of 1,536 cohort members were identified as having died. The observed mortality, by cause, was compared with the expected based on U.S. mortality rates, standardized for age, race, and calendar time. Analyses by length of exposure, latency, age at first exposure, calendar year of first exposure, and type of products were performed. The study confirmed that the vinyl chloride workers experience a significant mortality excesses in angiosarcoma (15 deaths), cancer of the liver and biliary tract (SMR = 641), and cancer of the brain and other central nervous system (SMR = 180). In addition, the study also found a significant mortality excess in emphysema/chronic obstructive pulmonary disease (COPD) (SMR = 179). On the other hand, the study did not find any excess in either respiratory cancer or lymphatic and hematopoietic cancer. This study also found an increase in biliary tract cancers, independent from liver cancer. PMID- 1928110 TI - A comparison of occupational data from death certificates and interviews. AB - A comparison was made of the occupational data reported on the death certificates of 586 men with their employment history obtained by interviews. Agreement was assessed for 19 occupational and 14 industrial categories of usual employment, with the highest levels of concordance (greater than or equal to 80%) found for agricultural, medical, and public administration activities. Between the two sources of information, there was overall agreement of 56% for usual occupation and 51% for usual industry of employment. Concordance was highest among the 68 self-respondents (usual occupation 66%; usual industry 53%). Among the 518 surrogates, spousal agreement was highest (58% for occupation and 51% for industry). For other surrogate types, agreement was 49% for both industry and occupation. Agreement varied by duration of employment and by level of education, with concordance tending to increase as length of employment and educational attainment rose. These relationships remained when examined by respondent type. Evaluation of agreement levels by age and other study subject characteristics showed little effect on concordance. Review of verbatim data from the interviews and death certificates revealed that most disagreements could be attributed to coding problems caused by vague or misleading information on the death certificates, although some disconcordance was due to uncodable and missing information in the interview history. Based on results from this and prior studies, the value of occupational data derived from death certificates in epidemiologic studies may be limited, although the addition of explicit instructions on the death certificate itself may aid in providing more useful and complete information for usual employment. PMID- 1928111 TI - A retrospective cohort mortality study of blending and packaging workers of Mobil Corporation. AB - This retrospective cohort mortality study examined 2,467 workers in lubrication products blending and packaging (B&P) operations at two refineries of Mobil Corporation between January 1, 1945 and December 31, 1978. Ninety-seven percent were male. Compared with U.S. males, there were significantly fewer deaths observed among males due to all causes, external causes, and diseases of the circulatory, respiratory, digestive, and genitourinary systems. Deaths observed from all cancer were fewer than expected, although not statistically significant. No statistically significant excess cause-specific mortality occurred at B&P facilities combined or separately. Nonsignificant increases in mortality were observed for cancers of the stomach, large intestine, prostate, the category of "other lymphatic tissue" cancer, and leukemia and aleukemia. Analyses demonstrated a statistically significant pattern of increasing SMR with employment duration for "other lymphatic tissue" cancer. Within the highest cumulative duration of employment category, the excess was confined to workers after 30 or more years since first employment. Although the interpretation of cancer mortality patterns is limited due to small numbers of deaths, the absence of associations with specific B&P departments is evidence against a causal interpretation. PMID- 1928112 TI - Solvent exposure and the risk of slips, trips, and falls among painters. AB - This study evaluated risk factors for injurious and noninjurious slips, trips, and falls among painters and investigated the hypothesis that exposure to solvents influenced the risk of such accidents. The data were collected longitudinally over an 11 month period. Weekly self-administered questionnaires detailed paint solvent exposure; work-related slips, trips, and falls (STFs); and potentially hazardous job tasks and environmental conditions. An initial questionnaire ascertained personal data, such as age, solvent exposure history, and alcohol consumption. During the study, 2,088 person-weeks of data were collected. Some participants provided many weeks of data, while others responded sporadically. Exposure to potentially hazardous environmental conditions was significantly related to the occurrence of STFs during a week. Several measures of solvent exposure were evaluated for their effect on STFs. Low solvent exposure during a week significantly increased the occurrence of slips, trips, and falls compared to no exposure. Moderate and high weekly exposure were not associated with increased risk, however. Week-to-week variability in the amount of solvent exposure was a strong positive predictor of STFs. Further analysis showed that both increases and decreases in solvent exposure between the preceding 2 weeks and the week of the STF were positively related to the risk of such events. The strongest effect was observed for exposure increases over the preceding 2 weeks. Overall, the results suggest that solvent exposure variability may increase accident risk, and possible explanations are explored. PMID- 1928114 TI - A cross-sectional study of pulmonary function among workers exposed to multimetals in the glass bangle industry. AB - Spirometric lung functions were evaluated in 220 asymptomatic glass bangle workers exposed to the salts of various heavy metals, such as arsenic, lead, zinc, copper, manganese, cobalt, cadmium, and selenium, which are used as coloring agents in the manufacture of glass bangles. The mean values of various spirometric variables (viz. FVC, FEV1, IMBC, and PEFR) were within normal range (more than 80% of the predicted values) in both smoking and nonsmoking glass bangle workers and did not reveal any significant differences in comparison with those observed in the unexposed controls. However, variables such as FEV1/FVC% ratio, FEF25-75 and FEF75-85 were reduced significantly (p less than 0.001) in the exposed group. The reduction was more marked in the smoking glass bangle workers indicating additive effect of cigarette smoking on the small airways. The exposed group showed a significantly higher prevalence (16.3%) of respiratory impairment in comparison to that observed in the controls (7.9%) as a result of exposure to various metals in the work environment (p less than 0.01). The respiratory impairment observed in the exposed group indicated primarily restrictive pattern of pulmonary abnormality (10.4%), while the controls revealed only 1.1% prevalence of this disease (p less than 0.001). The effect of the duration of exposure on the prevalence of respiratory impairment in the glass bangle industry revealed significantly higher prevalence (p less than 0.05) in those who worked for more than 10 years (23.0%) than in those who worked for less than 10 years (10.8%) thereby indicating that the duration of exposure is directly related to the prevalence of respiratory impairment. PMID- 1928113 TI - Occupational asbestos exposure and mesothelioma risk in Los Angeles County: application of an occupational hazard survey job-exposure matrix. AB - We evaluated the newly available National Institute for Occupational Safety and Health (NIOSH) National Occupational Hazard Survey (NOHS) job exposure matrix (JEM) by considering mesothelioma risk from asbestos exposure. We applied this system (NOHS-JEM) to the Los Angeles County Cancer Surveillance Program (CSP) to see how many cancer cases could be assigned asbestos exposure and how asbestos exposure affected mesothelioma risk. Using the same CSP data, our "experts" classified asbestos exposure simply by occupation and industry. Both exposure classifications were divided into low and high; the NOHS-JEM by the number of exposed people per couplet, and ours by judgements of intensity. Odds ratios (OR) for mesothelioma risk for low and high asbestos exposure for the NOHS-JEM were 2.0 (95% C.I. 1.2-3.4) and 2.5 (95% C.I. 1.2-4.8). For ours, corresponding risks were 1.6 (95% C.I. 1.1-2.4) and 6.3 (95% C.I. 2.5-15.1). Our system was able to assign more cases to couplets then the NOHS-JEM (35,895 to 22,369). Three limitations of the NOHS-JEM were that many occupation-industry couplets were not classified at all, many couplets associated with past asbestos exposure (before the 1972-1974 NOHS survey) were not classified as asbestos exposure, and no assessment of intensity was made. These limitations may apply to other exposures and should be carefully considered before the NOHS-JEM is applied to other case control studies. PMID- 1928115 TI - Cancer mortality among Danish molders. AB - This study was set up to investigate potential chronic health effects associated with molding in the foundry industry. For this purpose, a cohort of 632 male molders was followed through 10 years with regard to cause-specific mortality. Comparisons were made with another cohort of skilled workers. The mortality from cancer was increased among the molders (standardized mortality ratio 152, 95% confidence interval 100-221), mainly because of an excess number of deaths from bladder cancer (standardized mortality ratio 896, 95% confidence interval 329 1,949). It is suggested that certain mold types may emit bladder carcinogens. In addition, phenols, cresols, and aldehydes in the foundry work atmosphere might act as tumor promoters. PMID- 1928116 TI - Mesothelioma in the London area. PMID- 1928117 TI - Demonstration of asbestos fibers in a ten-year-old sputum sample. PMID- 1928118 TI - ACGIH TLVs: a critical analysis of the documentation. PMID- 1928119 TI - Finding common ground: two pharmacists on Capitol Hill. PMID- 1928121 TI - How many hospital pharmacists? PMID- 1928120 TI - Hospital executives give pharmacy directors high marks. PMID- 1928122 TI - Why pursue a residency? PMID- 1928123 TI - Dealing with unfair criticism from a superior. PMID- 1928124 TI - Caution advised with quality assurance consultants. PMID- 1928125 TI - Disturbing susceptibility pattern for ciprofloxacin. PMID- 1928126 TI - Labeling of nonprescription quinine needs revision. PMID- 1928127 TI - More to the E-Ferol case than presented. PMID- 1928129 TI - Assuming responsibility for improving quality. PMID- 1928128 TI - Measuring and improving quality. PMID- 1928130 TI - Quality assurance to quality improvement: measuring and monitoring pharmaceutical care. PMID- 1928131 TI - Quality and outcome: pharmacy's professional imperative. AB - Societal forces behind the increased use of outcomes to measure the quality of health care are described, and continuous improvement of outcomes as a goal for pharmacy is discussed. Consumerism, the demands of the aging American population, and problems of access to care for many Americans have helped to bring about an examination of quality. The effectiveness of clinical decision-making methods has been challenged. The Joint Commission on Accreditation of Healthcare Organizations now seeks to examine whether quality care is being provided, rather than whether the capacity exists to provide it. Inspection against criteria to determine quality will be superseded by a goal of continuous improvement. Traditional drug-use evaluation needs to go beyond collection of data and confrontation of noncompliant prescribing. Multidisciplinary quality improvement efforts should focus on patient outcomes; the goal should be to prevent all errors, rather than to not exceed some tolerable rate of errors. Pharmacists and risk managers should share information. Documentation of quality assurance efforts will be required. Drug-use evaluations should include assessment for therapeutic failure. Pharmacy quality improvement efforts can improve patient care and expand the pharmacist's role on the health-care team. PMID- 1928132 TI - Paradigm for the management of patient outcomes. AB - Health-status measurement is discussed, and a paradigm for the management of patient outcomes is described and applied to a patient case. Challenged not only to eradicate disease but to improve health, today's health-care professionals must examine the structure, process, and outcomes of care to ensure that optimal care is provided. Techniques for measuring outcomes have been developed; important indicators are functional status, general well-being, and the patient's assessment of care. An interdisciplinary team of physicians, social scientists, and public policy experts at The Health Institute, New England Medical Center, Boston, Massachusetts, studies ways of monitoring and improving the quality and efficiency of care. The team, which now includes a pharmacist, is working to develop practical systems of care whose outcomes can be tested in patients at the medical center. The paradigm developed for the management of patient outcomes begins with evaluation based on results of history, physical examination, and diagnostic tests. Problems and goals (therapeutic endpoints) are then defined, and the safest, most effective, and least costly treatment is selected. Treatment is monitored for subjective and objective results and adjusted as necessary. The achievement of each endpoint contributes to improvement of the patient's health. Knowledge of health-status measurement will enable pharmacists to increase their contribution to patients' health. PMID- 1928133 TI - Framework for continuous quality improvement in the provision of pharmaceutical care. AB - Implementation of the continuous quality improvement (CQI) process by health-care organizations is described. CQI involves a chain of events: Improvement in quality leads to decreased costs because of less rework, fewer mistakes, fewer delays, and better use of people and materials; productivity improves; better quality and lower price facilitate capturing the market, staying in business, and providing more jobs. The implementation of CQI within an organization involves the development, standardization, and deployment of standard methods and the use of daily management, cross-functional management, policy management, departmental management, and quality control circles to maintain, improve, or innovate standard methods. An organization's standard methods, key indicators (indicators for measuring performance of the organization's key functions), and standards emanate from its vision and mission statements and midterm and short-term strategic plans. In a quality control audit, an agreed-upon method, as monitored through a key indicator, is used to measure a result against an established standard; when a problem is detected, a quality control diagnosis is conducted and the method is changed if necessary. Use of this process requires the creation of standard methods for all important aspects of the organization's services, including operations, clinical services, and training of personnel. Health-care managers can use the principles of CQI in assessing the quality of care provided. PMID- 1928134 TI - Development of medication-use indicators by the Joint Commission on Accreditation of Healthcare Organizations. AB - The development of indicators for monitoring medication use is described. The Joint Commission on Accreditation of Healthcare Organizations is establishing a national database for use in measuring performance. Initially, indicators were developed for specialties or clinical departments and for disease entities or procedures; now, indicators for key functions that cross departmental and specialty lines, such as medication use, are under development. An interdisciplinary core group constructed a medication-use flow chart depicting prescribing, dispensing, administering, and monitoring patient response; systems management/control was recognized as a fifth component. Sixteen processes were identified for which indicators were developed. Proposed indicators are now being tested in a small number of hospitals. The indicator data will enable institutions to identify areas for improvement. Although the Joint Commission will not use indicator rates per se to determine accreditation, it will ask an institution to provide an interpretation of indicator data that differ markedly from previous data or data for comparable institutions and to review its strategy for analyzing the rates. Use of indicator data will enhance the accreditation process by allowing for ongoing monitoring of particular aspects of performance between onsite surveys. PMID- 1928135 TI - Selecting, developing, and evaluating indicators. AB - A process for selecting and evaluating indicators for use in monitoring the quality of patient care is described. An indicator is a quantitative measure that provides information and reveals ways in which care could be improved. It is a specific set of conditions whose presence signals that the care being provided should be examined. A sample medication-use outcome indicator is discussed to illustrate the steps of indicator evaluation in a paradigm proposed by the National Demonstration Project on Quality Improvement in Health Care. Indicators must be selected according to the needs of the institution: the frequency with which the set of conditions is likely to occur, the risk involved, and the institution's goals and capabilities. Documented data on the indicator must exist and must be adequate for evaluation of care. Analysis and interpretation of the data and a plan for using the information are discussed. For the use of indicators to succeed in improving the quality of care, the total institution must be committed to the process. Pharmacy quality assurance efforts need to move from evaluation of the use of specific drugs (i.e., focus on the product) to continuous measuring, monitoring, and quality improvement. PMID- 1928137 TI - Preliminary report of the ASHP Quality Assurance Indicators Development Group. PMID- 1928136 TI - A mid-sized hospital's experience in indicator data collection. AB - A hospital pharmacy department's experience in selection and use of indicators for measuring quality of care is described. At a 410-bed community teaching hospital, indicators were selected that would use data the department was already collecting. For the first indicator, "Patients on total parenteral nutrition (TPN) experiencing acid-base disorders," the goal was for no more than 20% of patients on TPN to have blood pH values outside the normal range, but 35% of patients were found to be outside the range. The standard TPN formula was examined and changed, after which only 16% of patients had pH values outside the normal range. For the second indicator, "Patients on TPN having negative nitrogen balance results," and the next two indicators, based on data available from the department's pharmacokinetics service, a similar process was followed. The department next examined incident reports and adverse drug reaction reports, categorized the drug-related problems represented, and established the indicator, "Patients on [nursing unit X] experiencing category 4 drug-related errors." Problems with indicator use included determining how an indicator relates to the quality of care and knowing how to analyze the data once they are collected. To maintain stature within their institutions by helping with the overall quality improvement effort, pharmacy departments need to expeditiously institute the use of indicators. PMID- 1928138 TI - Hospital administrators' perceptions of pharmacy directors. AB - The results of a national survey of hospital administrators' perceptions of pharmacy directors are reported. A questionnaire was mailed to a random sample of 1000 hospital administrators nationwide. The questionnaire asked each administrator to rate the managerial skills of pharmacy directors in general and the pharmacy director at his or her institution on a 5-point scale. The value the administrator placed on clinical pharmacy services was investigated, as was the administrator's knowledge of the education of the pharmacy director and the reporting structure between administrator and pharmacy director. The net response rate was 47.8% (478 usable replies). The hospital administrators believed that pharmacy directors in general need to improve their relationship with the nursing staff, their basic managerial skills, and their communication skills. They believed that the pharmacy director at their own institution excelled at keeping up with progressive pharmacy practice, inventory management, and interacting with the pharmacy and therapeutics committee. The administrators indicated that it is very important for the pharmacy department to be involved in therapeutic drug monitoring and medication counseling and to be progressive in their offerings of services. Hospital administrators had a positive perception of the abilities of pharmacy directors but believed that there is still room for improvement. PMID- 1928139 TI - Checking of unit dose cassettes by pharmacy technicians at three Minnesota hospitals. AB - A pilot project in which pharmacy technicians were trained to check unit dose cassettes filled by other technicians is described. With the approval of the state board of pharmacy, the Minnesota Society of Hospital Pharmacists (MSHP) conducted the nine-month project in three hospitals with different types of unit dose drug distribution systems. Twenty-seven technicians underwent didactic and practical training and were then validated as checkers if they scored 99.8% accuracy in checking carts into which errors had been deliberately introduced by the pharmacist auditor. The performance of validated technicians was audited monthly, and failed audits had to be repeated. Participating technicians did not check the preparation of first doses or extemporaneously prepared doses. In 100,000 doses audited, 60 errors by the validated checkers were identified. Of six technicians who failed a monthly audit, five passed a repeat audit. Pharmacists at the participating hospitals documented time they spent on clinical activities that would have been spent checking cassettes. In December 1990 a one year extension of the project, expanded to 10 hospitals, began. With strict quality control measures, specially selected and trained pharmacy technicians performed unit dose cassette checking with an accuracy of at least 99.94%. PMID- 1928140 TI - Pharmacist career ladder with clinical privilege categories. AB - The development of a career ladder program for staff pharmacists at a Department of Veterans Affairs (VA) medical center is recounted. Center policy required the establishment of clinical privileges for all pharmacists with direct patient contact and specified three VA privilege categories with increasing degrees of autonomy. The pharmacy department supported the need for all pharmacists to incorporate clinical activities into their daily practice but faced several problems, including inadequate instruction, insufficient incentives, fragmentation of clinical services, and subjectivity of measures of competence. In response, a pharmacy credentialing committee created a career ladder with three levels based on the established system of clinical privileges. Level A integrated basic clinical pharmacy knowledge with dispensing activities. Level B increased the number of clinical skills required and allowed the pharmacist to act as a therapeutic consultant. Level C incorporated the skills necessary for specialty practice. Instructors were designated for each clinical service area, readings and sample problems were assigned, and staff development presentations were improved. Objective tests of skills were designed. Combining the three levels on the career ladder with the three categories of clinical privileges formed a matrix of nine options for advancement. Pharmacists applying for advancement must master all requisite skills and submit relevant documentation. Each level carries a pay increase of 2%. A total of 53% of the staff pharmacists have participated in the program, which has had a favorable impact on staff retention. By combining nationally established categories of clinical privileges with an institution-specific career ladder, a pharmacy department helped ensure the consistency of services and promote the development of clinical practitioners. PMID- 1928141 TI - Using serum creatinine concentrations to screen for inappropriate dosage of renally eliminated drugs. AB - The impact on drug therapy and costs of a program to identify and correct unadjusted dosage in renally impaired patients is described. The program was instituted in May 1988 by the clinical pharmacy staff at a 272-bed hospital. Each day the clinical pharmacist uses laboratory data to list patients with serum creatinine concentrations greater than 1.5 mg/dL. The pharmacist screens the pharmacy profiles of listed patients and calculates creatinine clearance for patients receiving renally eliminated drugs. If, after reviewing the patient's medical record, the pharmacist judges that a dosage adjustment may be appropriate, he writes a confidential note to the physician. From May 1988 through June 1989, 2341 patients with elevated serum creatinine were monitored. During that period, 162 notes were left; recommendations from 142 (88%) of the notes were accepted by physicians. Most of the notes were written for patients receiving antimicrobials or histamine H2-receptor antagonists. The program, which requires 20-30 minutes of pharmacist time per day, avoided $5003 in drug acquisition costs and cost $2700 to administer during the one-year period. When the costs associated with drug preparation and administration are considered, net cost avoidance was $5040. An intervention program in which notes to physicians are written when patients with abnormal serum creatinine values are receiving drugs for which a dosage adjustment appears indicated (1) has medical staff acceptance, (2) helps to satisfy standards of the Joint Commission on Accreditation of Healthcare Organizations, and (3) saves money. PMID- 1928142 TI - Computer-based program for identifying medication orders requiring dosage modification based on renal function. AB - A computer-based program that enables staff pharmacists to quickly review medication orders written for renally impaired patients is described. Medication orders requiring dosage modification based on the renal function of the patients for whom they were written were being identified by a medical staff-approved pharmacist intervention program. However, staff pharmacists were unable to assess the orders easily and rapidly because of a lack of readily available patient data. In response, a computer-based intervention program was developed. Specific dosage guidelines for renally eliminated drugs in patients with renal dysfunction were entered into the pharmacy computer. An interface with the laboratory computer enables the pharmacy computer to access creatinine concentration or clearance values, perform calculations if necessary, and alert pharmacists to specific drug orders that may require modification. Such medication orders are flagged by the pharmacy computer during order entry. When a staff pharmacist judges that intervention is needed, he or she telephones the ordering physician or sends a note to the patient's nursing station. Over a two-month period, 1485 orders were identified as being potentially inappropriate. Physicians were contacted about 191 of the flagged orders, and they accepted the pharmacist's recommendation for 141 (74%) of these orders. The interventions resulted in a drug acquisition cost saving of $7082 over the two-month period. A computer-based program enabled staff pharmacists to easily and rapidly identify orders for renally eliminated agents that required modification, reduced the risk of adverse reactions, trimmed costs, and promoted the clinical dimension of pharmacy practice. PMID- 1928143 TI - Administration of whole blood, packed red blood cells, and platelets using a multipurpose infusion pump. PMID- 1928144 TI - Cost avoidance using syringe pumps to administer fat emulsion in a neonatal intensive-care unit. PMID- 1928145 TI - Comparison of pharmacy-based concurrent surveillance and medical record retrospective reporting of adverse drug reactions. PMID- 1928146 TI - Stability of doxorubicin hydrochloride in portable pump reservoirs. PMID- 1928147 TI - Detection methods and strategies for improving medication compliance. AB - The reliability of compliance detection methods and practical strategies for improving patient compliance with drug therapy are reviewed. Detection of noncompliance is a necessary prerequisite for adequate treatment. Noncompliance can be detected by indirect methods (e.g., self-report, interview, therapeutic outcome, pill count, computerized compliance monitors) or direct methods (e.g., biologic markers, tracer compounds, biologic assay of body fluids). In general, the direct methods of detection have a higher sensitivity and specificity than the indirect methods. Computerized compliance monitors are the most recent and reliable of the indirect-detection methods. Strategies for improving compliance involve identification of risk factors for non-compliance; development, with the patient's participation, of an individualized treatment plan that simplifies the regimen as much as possible; education of the patient, including information about his or her illness, instructions on how to take the prescribed medication correctly, and an explanation of the benefits and possible adverse effects of the therapy; and, if necessary, use of compliance aids such as medication calendars, special containers, caps, and dispensing systems, or compliance packaging. The patient should be taught to monitor his or her own treatment regimen. Follow-up monitoring by health-care professionals, including pharmacists, will also help ensure that the patient is complying with the treatment regimen. Health-care practitioners need to understand factors that contribute to noncompliance and to use effective methods for assessing and monitoring compliance in conjunction with strategies aimed at increasing compliant behavior. PMID- 1928149 TI - Clinical service contracts between hospital pharmacy departments and colleges of pharmacy. PMID- 1928150 TI - Fetal attraction. PMID- 1928148 TI - Public policy protects hospital quality assurance documents from discovery in litigation. PMID- 1928151 TI - Major trends in nosocomial viral infections. AB - Viruses have recently become appreciated as nosocomial pathogens. There is insufficient data to characterize trends in rates of viral nosocomial infections, but there have been major trends in methodologies and concepts. New groups of patients, such as infants and the elderly, are becoming appreciated as being at risk for serious nosocomial viral infections, whereas other groups, such as immunodeficient patients are expanding because of the epidemic of human immunodeficiency virus (HIV) infection and expanded use of immunosuppressive treatment. The continued addition of new viruses, such as HIV, human parvovirus B19, and rabies virus, to the list of potential nosocomial pathogens suggest that most human viruses can probably be serious nosocomial pathogens under the right circumstances. Advances in medical treatments and procedures, such as cadaveric dura mater grafts and laser treatment of warts, have provided new avenues for nosocomial transmission of viruses. Improved and wider availability of diagnostics promises to be a major force in improving our understanding and ability to prevent viral nosocomial infections. With these advances, viral diagnostic laboratories should become an important member of the infection control team. In parallel with trends in methodologies and concepts, there have been major advances in our understanding of ways to prevent some nosocomial viral infections. Application of these prevention measures is an important challenge to the infection control practitioner. PMID- 1928152 TI - An assessment of selective surveillance methods for detecting hospital-acquired infection. AB - Three selective surveillance methods were compared to a reference method in their ability to detect hospital-acquired infection (HAI) in patients occupying 122 beds of a district general hospital. The time for data collection was also assessed. The selective methods consisted of: (a) ward liaison surveillance (WLS), conferring with nursing staff twice weekly to determine patients with infections; (b) risk factor surveillance (RFS), the follow-up of patients with "clues" that indicated a risk of infection; and (c) laboratory-based ward liaison surveillance (LBWLS), the follow-up of positive microbiology reports by reviewing case records, in addition to conferring with nursing staff. The reference method consisted of total continuous clinical surveillance and the review of laboratory reports. During the 11-month period of the study, the reference method identified 306 HAI in 3,326 patients. LBWLS identified 71%, WLS 58%, and RFS 49% of HAI. The time for data collection (per week) was 7.75 hours for LBWLS, 4.3 hours for WLS, and 7.9 for RFS. In the United Kingdom, LBWLS was concluded to be an effective method of surveillance. PMID- 1928153 TI - Automated postdischarge surveillance for postpartum and neonatal nosocomial infections. AB - We developed a computerized record linkage system to determine whether it is feasible to use self-administered questionnaires to conduct large-scale, routine postdischarge surveillance for nosocomial infections among mothers and infants. We mailed questionnaires to 19,650 mothers of infants delivered at our institution who were discharged between January 1, 1988, and December 31, 1989. The questionnaire asked whether either mother or baby experienced infections, received an antibiotic, or was rehospitalized for an infection. Thirty-six percent of mothers returned the questionnaire. Seven hundred eleven (10%) of 7,033 replies reported 763 infections in mothers and 844 (12%) of 7,147 replies reported 968 infections in infants. These infections represented 4% of all women who delivered and 4% of all infants discharged. Since a minority of questionnaires were returned, these are likely to be conservative estimates of the occurrence of perceived infections. The most common maternal infections were mastitis (406 cases), urinary tract infections (185 cases), and endometritis (58 cases). The most common infections of infants were conjunctivitis (622 cases), diaper rash requiring antibiotics (169 cases), and umbilical infection (84 cases). Eighty-two percent of maternal infections reported after discharge were treated with antibiotics, as were 74% of infant infections. Infections reported during a 4-mont period were checked by a telephone call to the mother, who confirmed 17 (74%) of 23 reported maternal infections and 40 (70%) of 57 reported infant infections. Infections reported during a separate 3-month period were checked by contacting the patients' physicians, who confirmed 23 (48%) of 48 reported maternal infections and 19 (25%) of 76 reported infant infections. It is unclear how much of the low proportion of reported cases confirmed by physicians reflects overreporting by mothers and how much represents incomplete knowledge by physicians. In addition, some reported infections may have been acquired after discharge. Postdischarge surveillance via self-administered questionnaire identified twice as many apparent maternal infections and 12 times as many newborn infections as did concurrent prospective in-hospital surveillance. However, a number of important methodologic issues must be resolved. PMID- 1928154 TI - Risk-specific nosocomial infection rates. AB - Because nosocomial infection rates vary by hospital area and service, most infection control programs calculate area-specific rates to augment the reporting of their hospital-wide data. Rate development is often limited by the availability of appropriate specific denominator data to support important comparisons. Our university hospital reports a 20 month experience in which numerator data was collected as per the National Nosocomial Infections Surveillance System criteria for hospital-wide, high-risk nursery and ICU surveillance. These data were then combined with data in our hospital's patient specific denominator file. This has enabled the development of risk-specific infection rates based on the analytic control of important variables available in both the numerator and denominator files. We found rate differences that were length of stay cohort specific, hospital day specific, age specific, birthweight specific, and survival cohort specific when examining our data by both the cumulative incidence and incidence density methods. PMID- 1928155 TI - Control of nosocomial transmission of Clostridium difficile based on sporadic case surveillance. AB - The recognition of a cluster of antibiotic-associated nosocomial Clostridium difficile disease (NCDD) caused by serotype C in a surgical ward led to a hospital-wide NCDD surveillance and control program. The initial step included: (a) gas-liquid chromatography screening of inpatients' diarrheal stools; (b) enteric isolation precautions, cohorting and terminal room disinfection in wards with a cluster of two or more NCDD cases per month. During a 12-month period, the quarterly incidence of NCDD remained unchanged and six new clusters of serotype C, K, and H infections occurred, giving a global incidence of 1.5/1,000 admissions. C. difficile spores were recovered from 36.7% surfaces of case patient rooms versus 6.7% in control rooms. More intensive control measures were evaluated: (a) culture screening of inpatients' diarrheal stools; (b) early therapy, enteric isolation precautions, and daily meticulous room disinfection for each sporadic NCDD case. Surface disinfection reduced the contamination level four-fold (p = 0.04). In the following 12 months, no cluster occurred and the incidence of NCDD fell to 0.3/1,000 admission (protective efficacy 73%, 95% confidence interval: 46-87%). These observations suggest that early therapy, isolation precautions, and surface disinfection, focused on patients with sporadic NCDD detected by active surveillance, can prevent nosocomial transmission of C. difficile. PMID- 1928156 TI - Nosocomial infections in surgical patients: developing valid measures of intrinsic patient risk. AB - For surgeons or hospitals to compare their rates of wound infection meaningfully, the analysis must first control for the mix of intrinsic infection risk of their patients. Research over the past century has led to the development of several intrinsic risk indexes that can be used to stratify the wound infection rates so that valid comparisons can be made within risk strata. For an intrinsic risk index to be useful for comparing rates, it must control for all of the important intrinsic risk constructs; merely being statistically associated with infection rates does not ensure that a risk index will be useful. Understanding how a risk index can be both parsimonious and comprehensive requires consideration of the competing principles of multicollinearity and orthogonality. Various techniques of multivariate analysis are used to develop multivariate risk indexes, but the success of the process depends on having all of the important orthogonal risk constructs represented in the pool of predictor variables available for the analysis, either directly by variables in the pool or by demonstrated multicollinearity. Despite recent advances in risk measurement, many important questions remain. PMID- 1928158 TI - Striving for benchmark infection rates: progress in control for patient mix. AB - The outcome of clinical events has become the major focus for quality assurance programs in the United States. Assessment of outcome depends on the availability of accurate benchmark rates appropriate to the clinical situation. Although mortality, length of stay, cost, and other resource utilization measures are important outcome events for review, nosocomial infection is one of the best studied outcome events for which benchmark rates and distributions of rates are available. To monitor nosocomial infection acquisition, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has proposed indicators for wound infections after clean and clean-contaminated surgical procedures, for pneumonia in intensive care units (ICUs), and for intravascular device infections in ICUs. From the National Nosocomial Infections Surveillance (NNIS) system, we know that the mean rate of surgical wound infections (SWIs) for clean contaminated wounds is 2.7%. However, the range is too broad and depends on the types of surgical procedures and the patient risk factors in each category. As an example, the SWI rate for appendectomies is 2.2% while for colon surgery it is 7.1%. In addition, the patients should be stratified by underlying risk factors. For example, the NNIS risk index is composed of wound class, duration of surgery, and American Society of Anesthesiology score. Other commonly used severity of illness scores could be used, such as a comorbidity score or APACHE II. Other proposed JCAHO indicators are reviewed. Controlling for case mix and for severity of illness will be necessary for the development of benchmark infection rate distributions if clinical indicators are to be used as reliable quality assurance tools in the 1990s. PMID- 1928157 TI - Risk factors for postoperative infection. AB - During a 4-year period, we collected prospective epidemiologic data and intraoperative wound cultures from 1,852 surgery patients at a university affiliated community hospital in order to identify the critical risk factors for postoperative wound infections and study the impact of perioperative antibiotics on the bacteriology of infected wounds. Stepwise logistic regression analysis revealed four risk factors that were independent of each other and highly predictive for subsequent wound infection. These were the surgical wound class, American Society of Anesthesiologists physical status grouping, duration of surgery, and results of intraoperative cultures. Addition of other variables to our model did not increase the predicted probability of infection. Even though patients with positive intraoperative cultures had an increased rate of infection, this information had limited clinical utility. The predictive value of a positive culture was low (32%), false-positive rate was high (82%), and concordance with isolates from infected wounds was low (41% when both cultures were positive). Patients who had received perioperative antibiotics and who developed infections were frequently infected with organisms that were resistant to the perioperative drug regimen, compared with patients who had not received antibiotics. A better understanding of the variables that affect the epidemiology and pathogenesis of postoperative wound infection will enable us to make more valid comparisons of rates among hospitals, help us to develop more effective infection control strategies and provide us with more effective treatments. PMID- 1928159 TI - Effectiveness of an intervention program in reducing postoperative infections. Italian PRINOS Study Group. AB - From 1987 to 1989, the National Health Institute carried out a before and after intervention study in order to evaluate the effectiveness of active surveillance and of modification of patient care practices in reducing the incidence of postoperative infections. The initial study population consisted of 20 general and thoracic surgical wards in 12 hospitals; 11 wards were not able to complete the study and were therefore excluded from the analysis. In December 1988, after a 13-month period in which baseline infection rates were assessed in 4,096 patients, written protocols regarding modification of patient care practices were defined and applied. Effectiveness of intervention was evaluated comparing infection rates measured in a 6-month period in 1989 on 1,638 operated patients with those of the previous period. In the overall population, a reduction of 19% of nosocomial infections was observed after the intervention. When individual infection sites were considered, pneumonia rates were statistically significantly reduced by 39%; for the other infection sites the observed differences were not significant. Effectiveness of intervention varied by subgroups of wards. In three of the studied wards, surgical wound infections were significantly reduced by 72%, whereas in the remaining wards the intervention seemed to have no positive impact on infection rates. Nevertheless, the intervention seemed to have been effective in increasing the awareness of infection problems in two other wards. Results of the study suggest that a consistent reduction of postoperative infections can be achieved in surgical wards where usual patient-care practices differ from standard of patient care policies. Nevertheless, the observed variation in effectiveness of intervention by individual wards suggests that differences in structural and behavioral characteristics can affect the compliance with recommended standards. PMID- 1928160 TI - Analysis of risk factors for surgical wound infections following vascular surgery. AB - Although surgical wound infections (SWI) following implantation of prosthetic devices can be catastrophic and often require removal of the prosthesis, few studies have identified risk factors for these infections. We conducted a prospective multicenter study to identify risk factors for SWI. Of 561 vascular surgery patients enrolled in the study, 23 (4.1%) developed SWI. Multivariate analysis using logistic regression analyses identified surgery on lower extremities, delayed surgery, diabetes mellitus, past history of vascular surgery, and short antimicrobial prophylaxis (three doses of cefamandole) as independent risk factors for SWI. Consequences of SWI were serious; two (9%) died, 11 (48%) required reoperation, and five (22%) had their prosthesis removed. A risk index was developed using the independent risk factors for SWI identified by logistic regression analyses. When no risk factors were present, no SWI was observed (0 of 100), and the rate of SWI increased from 2.5% when one risk factor was present to 53.8% (7 of 13) when greater than or equal to 4 risk factors were present. PMID- 1928161 TI - Serratia marcescens surgical wound infection following breast reconstruction. AB - Surgical wound infections due to gram-negative bacilli have been rarely reported following breast implant surgery. From April to November 1989, four patients from one plastic surgeon's practice developed Serratia marcescens surgical wound infection (SWI) following breast reconstruction procedures with implantation of six expandable mammary implants. All six implants were removed for unabated S. marcescens SWI. Symptoms developed 13-161 days (median, 66 days) after surgery. When compared with nonexpandable silicone breast implants used during the period November 1, 1988, to October 31, 1989, expandable implants were associated with a greater risk of S. marcescens SWI (4/10 versus 0/11 patients, p = 0.04). Epidemiologic studies revealed that infection was associated with saline expansion of the implants performed in the surgeon's office. S. marcescens was cultured from a bag of commercial saline used on at least two of the four patients with SWI; the isolate from the saline and the three available patient isolates had identical serotype (O-undetermined:H4) and antimicrobial susceptibility patterns. Review of office procedures revealed that hands were not routinely washed before and aseptic technique was not used during the expansion procedure. Cultures of unopened bags of saline and an unused expandable implant were sterile. We hypothesize that multiple use of saline bags and nonsterile expansion technique extrinsically contaminated saline solutions and resulted in implant and/or surgical site infection. This investigation underscores the importance of avoiding multiple use of solutions intended for single use and of using aseptic technique when manipulating prosthetic devices. PMID- 1928162 TI - Epidemiology and control of nosocomial infections in adult intensive care units. AB - Traditional infection control measures in intensive care units (ICUs) have been directed at limiting person to person spread of infection and improving care of invasive devices. These measures often fail because they have little effect on patients' endogenous flora, which is an important source of infection in ICUs. Improvements in the design and aseptic care of invasive devices have helped to decrease the risk of progression from colonization to infection in individual patients. Interest is growing also in use of selective decontamination to decrease ICU infection rates. Despite these advances, basic hygiene and appropriate, prospectively monitored use of antibiotics remain essential components of ICU care. PMID- 1928163 TI - Nosocomial infection rates in adult and pediatric intensive care units in the United States. National Nosocomial Infections Surveillance System. AB - To determine which intensive care unit (ICU) infection rate may be best for interhospital and intrahospital comparisons and to assess the influence of invasive devices and type of ICU on infection rates, we analyzed data from the National Nosocomial Infections Surveillance System. From October 1986 to December 1990, 79 hospitals reported 2,334 hospital-months of data from 196 hospital units. The median overall infection rate was 9.2 infections per 100 patients. However, this infection rate had a strong positive correlation with average length of ICU stay (r = 0.60, p less than 0.0001). When patient-days was used in the denominator, the median overall nosocomial infection rate was 23.7 infections per 1,000 patient-days. Although there was a marked reduction in the correlation with average length of stay, this rate had a strong positive correlation with device utilization (r = 0.59, p less than 0.0001). To attempt to control for average length of stay and device utilization, we examined device-associated nosocomial infection rates. Central line-associated bloodstream infection rates, catheter-associated urinary tract infection rates, and ventilator-associated pneumonia rates varied by ICU type. The distributions of device-associated infection rates were different between some ICU types and were not different between others (coronary and medical ICUs or medical-surgical and surgical ICUs). Comparison of device-associated infection rates and overall device utilization identified hospital units with outlier infection rates or device utilization. These data show that: (1) choice of denominator is critical when calculating ICU infection rates; (2) device-associated infection rates vary by ICU type; and (3) intrahospital and interhospital comparison of ICU infection rates may best be made by comparing ICU-type specific, device-associated infection rates. PMID- 1928164 TI - Comparison of rates of nosocomial infections in neonatal intensive care units in the United States. National Nosocomial Infections Surveillance System. AB - To determine nosocomial infection (NI) rates among neonatal intensive care units (NICUs) that are useful for interhospital comparison, we analyzed data reported in 1986-1990 from 35 hospitals that have level III NICUs and used standard National Nosocomial Infections Surveillance protocols and NI site definitions. Overall rates of NI were calculated as the number of NI per 100 patients (overall NI patient rates) or the number of NI per 1,000 NICU patient-days (overall NI patient-day rates). A strong positive association was found between overall NI patient rates and the neonates' average length of stay, a marker for duration of exposure to important risk factors. No correlation was found between overall NI patient-day rates and average length of stay. However, a strong positive correlation between overall NI patient-day rates and a measure of device utilization (total device-days/total patient-days x 100) was found. Additionally, a positive correlation between overall NI patient rates and device utilization was found. Stratification among the three birthweight groups (less than 1,500 g, 1,500-2,500 g, greater than 2,500 g) did not eliminate the need to control for variations in these factors among NICUs. Device-associated, device-day infection rates, calculated as the number of umbilical or central line-associated blood stream infections per 1,000 umbilical or central line-days and the number of ventilator-associated pneumonias per 1,000 ventilator days, were not correlated with a unit's site-specific device utilization. These data suggest that calculation of device-associated NI rates in NICUs using device-days as the denominator helps to control for the duration of exposure to the primary risk factor and will be more meaningful for purposes of interhospital comparison. PMID- 1928165 TI - The pathogenesis and epidemiology of catheter-related infection with pulmonary artery Swan-Ganz catheters: a prospective study utilizing molecular subtyping. AB - To delineate the pathogenesis and epidemiology of catheter-related infection with Swan-Ganz pulmonary artery (PA) catheters, a prospective clinical study of hospitalized adult medical and surgical patients was done. Role of catheter material was assessed by randomizing insertions to heparin-bonded PA catheters made of polyvinylchloride or polyurethane. Sources of infection and pathogenesis were studied by culturing skin, the introducer, the PA catheter tip, all hubs, infusate from each lumen, and the extravascular portion of the PA catheter beneath the external protective plastic sleeve. Concordance between isolates from sources and infected catheters was determined by speciation, antibiogram, and for coagulase-negative staphylococci, plasmid profile analysis. Risk factors for infection were determined by stepwise logistic regression. Overall, 65 (22%) of 297 Swan-Ganz catheters showed local infection of the introducer (58 catheters) or the intravascular portion of the PA catheter (20 catheters); only two catheters (0.7%) caused bacteremia. Eighty percent of infected Swan-Ganz catheters (the introducer or PA catheter) showed concordance with organisms cultured from skin of the insertion site, 17% with a contaminated hub and 18% with organisms contaminating the extravascular portion of the PA catheter beneath the sleeve. Isolates from infected PA catheters were most likely to show concordance with concomitantly infected introducers (71%). Cutaneous colonization of the insertion site with greater than 10(2) cfu/10 cm2 (relative risk [RR] 5.5; p less than 0.001), insertion into an internal jugular vein (RR 4.3; p less than 0.01), catheterization greater than 3 days (RR 3.1; p less than 0.01), and insertion in the operating room using less stringent barrier precautions (RR 2.1; p = 0.03) were each associated with a significantly increased risk of catheter related infection. The risk of bacteremic infection with Swan-Ganz catheters is now low, in the range of 1%, with reasonable care. Swan-Ganz catheters are vulnerable to contamination from multiple sources, but the patient's skin is the single most important source of organisms causing invasive infection, which in most cases involves the introducer rather than the PA catheter. Heavy colonization of the insertion site, percutaneous insertion in the internal jugular vein rather than subclavian vein, catheterization longer than 3 days, and insertion with less stringent barrier precautions significantly increase the risk of catheter-related infection. These findings hold promise for application to management of Swan-Ganz catheters and research in catheter design to reduce the risk of catheter-related infection. PMID- 1928167 TI - Health care data, the epidemiologist's sand: comments on the quantity and quality of data. AB - Massive amounts of health care data are currently available for epidemiologic review through improvements in computerization and electronic communication. Multiple abstracts of patient care data are collected, stored, retrieved, and analyzed to study health care practice and outcome. The high level of variation in data from these sources is noted. Examples of these data collections are reviewed and the issues of the quality of these data for research and evaluation are discussed. Increased amounts of poor quality data will not be helpful. Collections from the National Center for Health Statistics and other sources are cited as models for improved standards for quality data banks and registries, including the Centers for Disease Control National Nosocomial Infections Surveillance collection. Throughout, a metaphor relating quality of sand for the production of lens instruments to view scientific change is used. PMID- 1928166 TI - Nosocomial infection rate as a function of human immunodeficiency virus type 1 status in hemophiliacs. AB - As part of a prospective cohort study initiated in 1983, the human immunodeficiency virus type 1 (HIV-1) status has been periodically determined for patients with clotting disorders (hemophilia A or B, von Willebrand's disease, miscellaneous). The University of North Carolina Hospitals has conducted comprehensive surveillance for nosocomial infections (NI) using modified Centers for Disease Control criteria since 1980 and entered this information in a computerized data base. Cross-matching of our NI data base and hemophiliac/HIV-1 study data base for the time period 1980-1989 revealed that 13 NI occurred in 11 patients during 659 hospitalizations (5,723 hospital days). NI rates per 100 admissions (per 1,000 hospital days) by HIV-1 status were as follows: HIV-1 negative = 0.91 (1.18), HIV-1 positive pre-AIDS = 1.65 (1.84), and AIDS = 6.67 (6.48). NI occurred with a similar frequency in HIV-1 positive pre-AIDS hemophiliacs and HIV-1 negative hemophiliacs (Fisher's exact test, p greater than 0.10). However, NI occurred more frequently in hemophiliacs with AIDS versus HIV 1 positive or negative hemophiliacs (Fisher's exact test, p less than 0.05). We conclude that HIV-1 infection does not appreciably alter the risk of developing a NI, but that patients who have progressed to AIDS are at significantly increased risk of developing a NI per hospital day or per hospitalization. PMID- 1928168 TI - Methicillin-resistant Staphylococcus aureus: implications for the 1990s and effective control measures. AB - Data from around the world verify the escalating incidence of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Since MRSA are spread primarily on the hands of health care workers, rates of infection are a function of infection control activities within institutions. Moreover, infections with MRSA are serious and often life-threatening. Thus, there are compelling medical and ethical reasons to invest in control measures. Currently available data suggest the efficacy of three measures: (a) identification of the entire patient reservoir (cases and carriers) for purposes of isolation; (b) strict handwashing between patients to prevent transmission; and (c) treatment of the carrier state in health care workers and patients during periods of high infection rates with safe and effective topical agents such as mupirocin. PMID- 1928169 TI - Assigning responsibility: using feedback to achieve sustained control of methicillin-resistant Staphylococcus aureus. AB - Sustained control of endemic methicillin-resistant Staphylococcus aureus (MRSA) originating from multiple sources has not been reported. We describe a simple, inexpensive program based on feedback to physicians that resulted in significant reduction of nosocomial MRSA. When nosocomial cases were identified, the epidemiologist contacted the team resident to encourage increased emphasis on hand washing. Handouts, periodic hand cultures of house staff, and monthly presentations at morning report were also employed. In the first 15 months, nosocomial MRSA decreased from 1.025 to 0.508 cases per 1,000 patient days (p less than 0.01). Monthly rates were significantly decreased for 9 months of 1989 and the first 2 months of 1990. Feedback and assignment of responsibility resulted in a 50% reduction in nosocomial MRSA that has been sustained for 15 months. PMID- 1928170 TI - A seven-year experience with methicillin-resistant Staphylococcus aureus. AB - From July 1983 through June 1990, 319 patients with methicillin-resistant Staphylococcus aureus (MRSA) were identified at the University of California, Davis Medical Center. Initially, our goal was eradication of MRSA from the hospital flora. Our approach was: (a) immediate notification of all MRSA isolates by the microbiology laboratory; (b) strict isolation; (c) cohorting; (d) bathing patients with an iodophor; (e) surveillance cultures of patients and staff; (f) treatment of all colonized persons; and (g) strict isolation on readmission. Control of spread was achieved but eradication was not. In 1987 our strategy was modified in order to establish the least restrictive methods to maintain control of the spread of MRSA. After notification by the microbiology laboratory, we now require: (a) contact isolation; (b) surveillance cultures of patients associated with each new case; and (c) contact isolation for all MRSA patients on readmission. Strict isolation and employee culturing are used only during major outbreaks. We have averaged four new cases of MRSA per month over the 7-year period, including four major outbreaks. Since 1987, we have averaged only three new cases per month with one major MRSA outbreak. Annual cost savings of greater than $50,000 have been realized through the policy modifications. We conclude that the use of contact isolation with some modifications has saved time and money and has successfully controlled the spread of MRSA in our university hospital. PMID- 1928171 TI - Reemergence of epidemic methicillin-resistant Staphylococcus aureus in a general hospital associated with changing staphylococcal strains. AB - An epidemic of methicillin-resistant Staphylococcus aureus (MRSA) infections involving 323 patients occurred at the University of Cincinnati Hospital from 1977 to 1981. Subsequently, endemic MRSA persisted in the hospital for 6 years, until 1987, when a new epidemic began with 223 patients becoming infected over 3 years. Between the two epidemics, there was a major change in the MRSA recovered from infected patients, as demonstrated by three epidemiologic markers. Antibiograms showed that the tetracycline-resistant MRSA involved in the first epidemic was replaced by tetracycline-susceptible MRSA in the second epidemic; bacteriophage typing indicated that the original epidemic strain, D11/83A/85, had been replaced by new strains, many of which were susceptible to phage 54; and restriction endonuclease analysis of plasmid DNA confirmed that a single strain was involved in the first epidemic and that multiple strains were present in the second epidemic. The epidemiology of MRSA infections in the hospital changed with the change in staphylococcal strains. The first epidemic was hospital based with most infections occurring in surgical patients, and the burn unit was the major reservoir. In contrast, 28% of the patients in the second epidemic had community acquired infections, and nursing home patients were an important source of these infections. Also, 29% of the hospital-acquired infections in this epidemic occurred in nonsurgical patients. This time the burn unit was not a reservoir of infection, but other intensive care units were. The increased diversity of strains of MRSA in the second epidemic might be related to increased transmission in the community and more widespread transmission in the hospital. PMID- 1928172 TI - New laboratory techniques for hospital infection control. AB - The clinical microbiologist has important responsibilities in hospital infection control. Duties include participating in hospital-wide infection control activities (especially the infection control committee), recovering and identifying accurately the organisms responsible for nosocomial infection, characterizing antimicrobial susceptibility of many of these nosocomial pathogens, reporting in timely fashion laboratory data relevant to infection control, carrying out the few routine microbiologic studies of the hospital environment that are useful, supporting investigations of specific hospital infection problems as they arise, and providing special typing studies when necessary to establish similarity or difference of organisms. In the past decade, improvements in laboratory instrumentation and/or procedures have provided dramatic help to infection control efforts in several of these areas. Among these are new techniques for more rapid detection and differentiation of organisms and improved systems of reporting for both patient data and trend analysis. Perhaps the most dramatic advances have come in special procedures for examining (typing) hospital organisms for similarity or difference; here, molecular and other techniques have permitted more definitive examination of a wider range of organisms than previously was possible. With health care resources in the United States now at a premium, the current and future challenge for laboratories is to make their participation in infection control more efficient as well as effective. Establishing adequate quality control of methods and obtaining clinical data to allow correct interpretation will be crucial for efficient use of the new typing procedures. Deciding when these techniques are needed and whether they should be performed on site also will be an important part of this process. PMID- 1928173 TI - Contour-clamped homogeneous electric field gel electrophoresis as a powerful epidemiologic tool in yeast infections. AB - To examine the longitudinal and cross-sectional patterns of yeast colonization in critically ill patients using genotypic characteristics defined by contour clamped homogeneous electric field (CHEF) gel electrophoresis, 322 clinical isolates of Candida species were prospectively collected from 29 critically ill patients under routine surveillance over a 6-month period. All isolates, recovered from multiple anatomic sites and from the same sites on different days, were characterized by several identification methods (germ tube test), phenotyping (API system), and genotyping (electrophoretic karyotyping). Electrophoretic karyotype (EK) was determined using pulsed field electrophoresis with the CHEF technique. We used a karyotyping system for Candida albicans (EK code) that facilitated intraspecies delineation. C. albicans colonized 83% of the 29 patients. Candida sp. strains isolated from an individual patient had an identical EK pattern, even when isolated from different body sites, and remained the same over a prolonged period, up to 140 days. EK delineated not only the different Candida species, but also different strains of C. albicans. Strains of C. albicans isolated from different patients were distinguished using the EK pattern, but not API system. Minor variations in EK pattern could be demonstrated in a minority of strains recovered from four patients and were interpreted as chromosomal rearrangements between parent strains. Severe candidal infections, including eight episodes of fungemia, occurred in 11 of 29 patients (38%). All patients had been previously colonized with strains with identical EK patterns. Infection occurred a mean of 25 days after initial surveillance cultures grew yeast. No horizontal transmission could be demonstrated during the study period. In conclusion, EK is a reproducible, stable marker allowing inter-, as well as, intraspecies Candida strain delineation. EK strain delineation is a useful tool in candidal epidemiologic and pathogenic studies. Yeast colonization with the same strain preceded infection in critically ill patients. PMID- 1928174 TI - New technology for sterilization and disinfection. AB - Sterilization with low temperature steam and formaldehyde is a well-known process in many European countries, but little known in the United States. It sterilizes reliably and reproducibly at temperatures greater than or equal to 65 degrees C. With a well-designed cycle, it leaves residues of formaldehyde on sterilized items below 5 micrograms/cm2, measured on a standard filter paper. Formaldehyde levels in air near the autoclave are well below official exposure limits, if at all measurable. Occurrence of late growers in bioindicators, and penetration of the sterilizing media into long narrow lumina, should be validated for new processes. Automated cleaning and disinfection in closed washer-disinfectors and flushing disinfectors are likewise processes relatively little known in the United States. Disinfection is achieved by a final rinse with hot water or steam. Washer-disinfectors are used for surgical instruments, nondisposable anesthesia and other equipment, flushing disinfectors for nondisposable bedpans, wash-bowls, urinals, and similar equipment. They clean well, washer-disinfectors excellently so, and disinfect reliably. With the use of such equipment in wards, surgical departments, and other areas, reliance on chemical germicides can be dramatically reduced and disposables can be replaced by disinfectable nondisposables. PMID- 1928175 TI - Inactivation of Mycobacterium tuberculosis and Mycobacterium bovis by 14 hospital disinfectants. AB - Epidemics of mycobacteria due to contamination of medical devices continue to occur. For this reason, we assessed the ability of disinfectants, generally used in hospitals for disinfecting noncritical and semicritical patient care items, to inactivate mycobacteria. A modified Association of Official Analytical Chemists' (AOAC) Tuberculocidal Activity Test, using Middlebrook 7H9 broth as the primary subculture medium and neutralization by dilution, was used to assess the ability of 14 hospital disinfectants to inactivate about 10(6) Mycobacterium tuberculosis and about 10(5) Mycobacterium bovis at 20 degrees C using 10- or 20-minute exposure. All products were tested for each organism using 10 penicylinders (P) and were prepared at the manufacturers' recommended use-dilution. Chlorine dioxide, 0.80% hydrogen peroxide plus 0.06% peroxyacetic acid, and an iodophor achieved complete inactivation (0 + P) of both M. tuberculosis and M. bovis. One quaternary ammonium compound with a tuberculocidal label claim, a quaternary ammonium compound without a tuberculocidal label claim, chlorine (approximately 100 ppm) and 0.13% glutaraldehyde/0.44% phenol/0.08% phenate were not effective (10 + P) against both M. tuberculosis and M. bovis. Another quaternary ammonium compound with a tuberculocidal label claim was tested against only M. bovis and found ineffective (10 + P). Glutaraldehydes (2% alkaline and 2% acid), a phenolic and chlorine (approximately 1,000 ppm) demonstrated complete inactivation of M. tuberculosis (0 + P) and good inactivation of M. bovis (1-3 + P). Two disinfectants, hydrogen peroxide and ethyl alcohol, provided differing results against M. tuberculosis and M. bovis. These studies have important implications for disinfecting semicritical patient care items. PMID- 1928176 TI - Infection control: the premier quality assessment program in United States hospitals. AB - The three decennial international meetings of the Centers for Disease Control have reaffirmed the national health priority for prevention of nosocomial infections. Moreover, the past 20 years have seen the institutionalization of the infection control practitioner and hospital epidemiologist. The epidemiologic activities of these two groups have included access to medical care, identification of risk factors, and both prevention and control of adverse nosocomial events. As such, they represent experience with issues commonly referred to as quality of care. It is argued that infection control not only is now but has been from its inception the premier quality assessment program in the United States. Moreover, it is the only activity in quality assessment that has been shown to be efficacious. PMID- 1928177 TI - Nosocomial infections from contaminated endoscopes: a flawed automated endoscope washer. An investigation using molecular epidemiology. AB - Approximately 1 year after purchase of one manufacturer's automated endoscope washing machine, we began to detect heavy contamination of upper gastrointestinal (UGI) endoscopes cultured after cleaning and disinfection in the washer. During the first 6 months of 1988, 77% of surveillance cultures (20-mL flush through the biopsy channel) were positive for gram-negative bacilli (median concentration, 10(5) cfu/mL), most frequently Pseudomonas aeruginosa serotype 10. During the first 19 months of use of the washer, nosocomial post-UGI endoscopy colonization or infections with P. aeruginosa increased 36%. Investigations show that endoscope contamination derives from a flaw in the design of the EW-10 washer: the detergent holding tank, inlet water hose, and air vents cannot be reliably disinfected and contain heavy biofilms that recontaminate the machine after it has been disinfected, as specified by the manufacturer, with glutaraldehyde. Only by rinsing machine-cleansed endoscopes with 70% alcohol followed by forced air drying has reliable disinfection been achieved. Since adaptation of terminal alcohol treatment and drying, post-UGI endoscopy colonization or infection by P. aeruginosa has declined threefold (p less than 0.001). Testing in other centers using the manufacturer's EW-10 or EW-20 washer has shown similar contamination. In three centers, including our own, postendoscopy infections by machine associated type 10 P. aeruginosa have been confirmed by demonstrating concordance between isolates from contaminated machines or endoscopes and from infected patients by immunoblot of whole cell lysates and by pulsed-field electrophoresis of DraI endonuclease-digested genomic DNA. This problem reaffirms the vulnerability to microbial contamination of water-containing apparatus and equipment in patient care and points up the critical importance of engineering design to prevent contamination. PMID- 1928178 TI - Current status of nosocomial infection control in extended care facilities. AB - The 1980s saw the birth and growth of the distinct field of infection control in the extended care facility (ECF). Major advances in the field during the last decade have been surveys documenting the magnitude of the problem of ECF nosocomial infections, descriptive studies of ECF nosocomial infections, descriptive studies of ECF epidemics, development of ECF infection control programs, and recognition of the unique problems of the ECF infection control program. As the field matures, areas that should receive additional attention during the upcoming decade include: analysis of the risk factors and consequences of ECF nosocomial infections; analysis of resident and institutional variables that predict nosocomial infection; and studies on the efficacy of both infection control programs and specific infection control measures. ECF infection control programs have benefited a great deal from hospital infection control, but ECF infection control problems are quite different and demand unique solutions. PMID- 1928179 TI - Surveillance and control of infections in long-term care: the Canadian experience. AB - In 1980, the Laboratory Centre for Disease Control, Health Protection Branch, Department of National Health and Welfare Canada, established the Bureau of Infection Control in response to a growing need for an infection control resource at the national level. Until that time, there had been no federal programs in Canada for surveillance and control of infections in health care facilities. Initial efforts in the development of infection control programs focused on acute care facilities. In 1985, a specific need was identified to develop better surveillance and control of infections in long-term care facilities. Several national initiatives have been undertaken to meet this need, including the preparation and publication of an infection control guideline specifically for long-term care facilities, a national survey of Canadian long-term facilities, and the stimulation of research to evaluate new criteria for nosocomial infections in a selected number of Canadian long-term care facilities. PMID- 1928181 TI - Human immunodeficiency virus transmission in health care settings: risk and risk reduction. AB - Surveillance data and case reports document that health care workers (HCWs) risk occupationally acquired human immunodeficiency virus (HIV) infection. Transmission of HIV to patients of an infected HCW during invasive procedures has also been reported. The risk to a susceptible HCW depends on the prevalence of HIV infection among patients, the nature and frequency of occupational blood exposures, and the risk of transmission per exposure. Blood exposure rates vary by occupation, by procedure, and by compliance with preventive measures. Future efforts to protect both HCWs and patients must include improved surveillance, risk assessment, study of postexposure prophylaxis, and an emphasis on exposure prevention, including development of safer medical devices, work practices, and personal protective equipment that are acceptable to HCWs and do not adversely affect patient care. PMID- 1928180 TI - Nosocomial infections in elderly patients in the United States, 1986-1990. National Nosocomial Infections Surveillance System. AB - We analyzed 101,479 nosocomial infections in 75,398 adult patients (greater than 15 years) that were reported to the National Nosocomial Infections Surveillance (NNIS) system between 1986 and 1990 by 89 hospitals using the NNIS hospital-wide surveillance component. Overall, 54% of the infections occurred in elderly patients (greater than or equal to 65 years). In the elderly, 44% of the infections were urinary tract infections (UTIs), 18% were pneumonias, 11% were surgical wound infections (SWIs), 8% were bloodstream infections (BSIs), and the remainder were infections at other sites. When we compared the infections in elderly patients with those in younger adult patients, ages 15 to 64 years, a far greater percentage of the infections in elderly patients were UTIs, and there were more pneumonias than SWIs. Elderly and younger patients with ventilator associated pneumonia were about 1.5 times more likely to develop a secondary BSI than those with pneumonia not associated with ventilator use. When the pathogens isolated from the infections were compared to those reported to the NNIS system in 1984, the percentage that were coagulase-negative staphylococci had increased in both elderly and younger patients. The patient died in 12% of all of the infections. Surveillance personnel reported that 54% of the infections in elderly infected patients who died were related to death compared with 59% in younger infected patients who died. When the infection was related to the patient's death, it was most often pneumonia or a BSI. The risk of an infection-related death was significantly higher when the infected patient developed a secondary BSI. Infection prevention efforts should target infections that occur frequently, are amenable to intervention, and have an adverse outcome. PMID- 1928182 TI - The Third Decennial International Conference on Nosocomial Infections. Historical perspective: the landmark conference in 1970. PMID- 1928183 TI - Epidemiology of hospital sharps injuries: a 14-year prospective study in the pre AIDS and AIDS eras. AB - The world pandemic of acquired immunodeficiency syndrome (AIDS) has focused enormous attention on the problem of accidental sharps injuries sustained by health care workers (HCWs) and the risk of occupationally acquired infection by human immunodeficiency virus (HIV). At the 1980 Conference, we reported a 4-year epidemiologic study (1975-1979) of sharps injuries in HCWs at our hospital. Using the same reporting system and analyses, we now report the epidemiology of sharps injuries in our center during the current AIDS era (1987-1988) and assess trends over the 14-year period. Despite greatly increased institutional efforts to prevent sharps injuries, the annual incidence has increased more than threefold (60.4 to 187.0/1,000 HCWs), reflecting better reporting and increased exposure. Reported injuries by house officers have increased ninefold. Adjusting for inflation, the direct costs of sharps injuries has increased sevenfold ($5,354 to $37,271/year). Environmental service HCWs (305.8 sharps injuries per 1,000 employees) now have the highest incidence in our center, followed by nursing personnel (196.5/1,000) and laboratory personnel (169.9/1,000), but as in 1975 1979, two thirds of all injuries occur in nursing personnel. Although phlebotomy team members have a very low risk per procedure (1/26,871 draws), their annual incidence is extraordinarily high, 407.0/1,000. Injuries continue to occur mainly during disposal of waste, linen, or used procedure trays (19.7% of all injuries), administration of parenteral injections or infusion therapy (15.7%), surgery (16.0%), blood drawing (13.3%), or recapping of used needles (10.1%). Making disposal units available at every bedside has reduced injuries from needle disposal two-fold since 1975-1979. With consistent application of a stringent postexposure protocol, and wide acceptance of the hepatitis B vaccine, we have had no sharps injury-related infections during the past 3 years. These data indicate the increasing risk, complexity and cost of sharps injuries in HCWs and the need for more innovative--ideally, technology-based--approaches to prevention. Certain groups of HCWs are at very high risk. Comprehensive postexposure protocols that are uniformly applied can provide substantial protection to exposed HCWs. PMID- 1928184 TI - Does knowledge of human immunodeficiency virus infection decrease the frequency of occupational exposure to blood? AB - Implementation of universal precautions is advocated to prevent exposure to human immunodeficiency virus (HIV) and other bloodborne pathogens. Critics of this approach argue that additional benefit can be derived by identifying and labeling patients known to be infected. Knowledge of HIV infection status could result in a reduced exposure rate by two mechanisms: (a) by motivating improved compliance with universal precautions, or (b) by allowing changes in procedure or technique not feasible for all patients. Compliance with universal precautions may reduce the frequency of some types of exposure but has not been associated with a reduction in the frequency of needlestick exposures in several studies. Despite the perception by some health care workers that awareness of HIV status will result in improved safety, no objective data have demonstrated a direct benefit from testing or identifying infected patients. Health care workers who recognize the presence of occupational HIV risk are apt to be motivated to practice universal infection control precautions and experience little additional benefit from testing individual patients. Health care workers in low prevalence areas may experience less incentive to comply routinely with universal precautions and selectively may be motivated when HIV infection is diagnosed in individual patients. However, routine testing in areas of low HIV prevalence is not likely to be cost effective. Until further research clarifies the efficacy and costs of universal precautions or HIV testing, infection control standards should maximize local autonomy in developing rational policies consistent with institutional needs. PMID- 1928185 TI - Postexposure chemoprophylaxis for occupational exposure to human immunodeficiency virus type 1: current status and prospects for the future. AB - Occupational exposures to the human immunodeficiency virus (HIV) continue to occur in the health care setting. Each such exposure is associated with risk for occupational infection. Although occupational HIV infections have been uncommon in health care workers, the occurrence of even one such infection is traumatic for the health care worker and his or her institution. To attempt to prevent infection following occupational exposures, some institutions and investigators have elected to offer postexposure chemoprophylaxis with zidovudine. Unfortunately, data describing the use of nucleoside analogues in animals and humans as antiviral chemoprophylaxis are quite limited and data simply do not exist that definitely support or refute their use in this setting. One can mount an equally reasonable argument for or against the use of these agents in this setting in 1990. This article reviews the available data regarding postexposure chemoprophylaxis, summarizes the clinical experience with zidovudine use for postexposure chemoprophylaxis to date, and evaluates prospects for additional chemoprophylaxis options in the future. PMID- 1928186 TI - Measuring the costs of nosocomial infections: methods for estimating economic burden on the hospital. AB - To compete more effectively for resources, it is increasingly important for infection control practitioners to estimate the costs of nosocomial infections and the amount of money their infection control programs save the hospital. Studies on costs should estimate both extra length of stay and extra costs attributable to infectious complications. Cost estimates should either adjust charges by a cost to charge ratio, which is relatively easy, or estimate hospital costs directly by detailed cost-accounting, which is comparatively more difficult. If there is insufficient time to measure costs concurrently in every infected patient, comparative studies can be done by comparing infected and uninfected patients matched on characteristics that control for the preexisting differences between them. Diagnosis-related groups and the number of diagnoses appear to be useful matching variables because they are strongly associated with both nosocomial infection and length of stay. The final results should be expressed as either potential or actual savings to the hospital, depending on whether significant reductions in nosocomial infection rates have been achieved. PMID- 1928187 TI - Transmission of measles in medical settings--United States, 1985-1989. AB - Measles cases reported to the Centers for Disease Control from 1985 to 1989 were analyzed to determine the characteristics of measles cases transmitted in medical settings. A total of 1,209 medial setting cases were identified, which represented 3.5% of all reported cases. Of medical setting cases, 66% (795) were in known or presumed patients and 28% (341) were in health care workers. The largest groups of health care workers with measles were nurses (101, 29.6%) and physicians (65, 19.1%). Health care workers acquired measles from patients (90.6%) and other health care workers (9.4%), and transmitted measles to patients, other health care workers, and family members. Of 333 (97.7%) health care workers with known measles vaccination status, 232 (68.0%) were eligible for vaccine; only 46 (19.8%) had received a documented dose. Twenty-nine percent of health care workers with measles were born before 1957, older than the age for routine measles vaccination. The relative risk of measles for physicians and nurses was 8.4 (95% confidence interval [CI], 6.6, 10.8) and 2.1 (95% CI, 1.8, 2.7) respectively, compared with nonhealth care workers of the same ages. In 1989 the Immunization Practices Advisory Committee (ACIP) recommended that health care workers be required to document two doses of measles vaccine or other evidence of measles immunity at the time of employment. Implementation of ACIP recommendations for health care workers and appropriate isolation precautions for known and suspected patients with measles could reduce the transmission of measles in medical settings. PMID- 1928188 TI - Response to a hospitalized case of measles at a medical school affiliated hospital. AB - A 27-year-old woman was diagnosed as having measles 2 days after being hospitalized for an unrelated complaint. Hospital personnel, medical housestaff, and students were considered at risk for developing measles infection. Over a 7 day period, measles vaccine was administered to individuals born in or after 1957. No secondary measles cases occurred in the hospital. An immediate response to the possibility of nosocomial measles transmission can be successfully undertaken, but ongoing preemployment or preenrollment school programs are more practical and potentially can have a higher rate of compliance. PMID- 1928189 TI - Recurrent group A streptococcal carriage in a health care worker associated with widely separated nosocomial outbreaks. AB - Nine postpartum infections (five bacteremias, three cases of endometritis without bacteremia, and one infected episiotomy site) caused by an M-nontypable, T-28 strain of group A Streptococcus occurred during a 9-week period in 1987. Seven cases were cared for by one obstetrician, who was also present in the delivery suite when the remaining patients delivered. This individual was found to be an anal carrier of group A Streptococcus with the same M and T types. During the cluster, the attack rate for vaginal deliveries performed by this individual was 18% (6 of 34 patients). The individual was treated with penicillin V (500 mg four times a day for 10 days), rifampin (600 mg twice a day for 5 days), and hexachlorophene showers. Surveillance cultures of the physician were negative 1 week, 1 month, and 3 months after completion of therapy. No additional cases were identified among the next 210 vaginal deliveries performed by this individual. Fourteen months after therapy, four new cases occurred during 2 days. The physician was found to be heavily colonized once again with the original strain of group A Streptococcus and was treated with rifampin (600 mg twice a day) and oral vancomycin (250 mg four times a day) for 7 days. An open-ended regimen of penicillin V (250 mg/day) and periodic surveillance cultures was begun. During the next 19 months, this physician performed 275 vaginal deliveries, one of which resulted in an M-nontypable, T-28 group A streptococcal infection, at a time when the physician's surveillance cultures were negative. It is unclear how long a colonized health care worker who causes nosocomial group A streptococcal disease must be treated or monitored, but there is some risk after more than a year. Long term surveillance or prophylaxis may be useful in some circumstances. PMID- 1928190 TI - Year 2000 objectives for preventing nosocomial infections: how do we get there? AB - In the late 1970s, the United States Public Health Service (PHS), in collaboration with public and private sector individuals and organizations, for the first time formulated national objectives for the prevention and control of disease. The PHS Year 1990 Objectives and Year 2000 Objectives both contain plans for preventing and controlling nosocomial infections. The Year 2000 Objectives contain goals for reducing infections that have been judged achievable, using existing prevention and control strategies. The specific Year 2000 Objectives targeting nosocomial infections can be divided into two categories: a) protecting the health care worker and b) protecting the patient. The Occupational Safety and Health Administration will play a major role in the upcoming decade in attaining the health care worker objectives. Reductions in patient nosocomial infections focus on surgical wound infections and infections in intensive care patients. Considerable work needs to be done in developing suitable nosocomial infection rate measures that adjust for patient case mix in order to assess progress toward achieving the objectives. Educational efforts targeted at entry-level health care providers and hospital epidemiologists must be strengthened. Government agencies, academic centers, industry, and professional organizations each have unique strengths and talents that can be collectively brought to bear on the problem. PMID- 1928191 TI - Preventing nosocomial pneumonia: state of the art and perspectives for the 1990s. AB - In the 1980s, nosocomial pneumonia became the second most common nosocomial infection in the United States. Gram-negative bacilli and Staphylococcus aureus were the most frequently isolated bacteria. Methods to improve the diagnostic sensitivity and specificity included transtracheal aspirates and bronchoscopy with protected specimen brush or bronchoalveolar lavage. Multivariate analysis was used to identify independent risk factors for pneumonia and fatality in different subsets of high-risk patients. Gastric pH and colonization were evaluated as risk factors for pneumonia in mechanically ventilated patients. Colonized respiratory therapy equipment and contaminated tubing condensate and in line medication nebulizers were suggested as possible sources of nosocomial pathogens. Staff education programs, the use of barrier precautions, and selective decontamination of the digestive tract were associated with reduced rates of lower respiratory tract infection. Despite a decade of progress in our understanding of nosocomial pneumonia, progress in the 1990s will undoubtedly include molecular epidemiologic techniques, appropriate application of risk factor data, and the use of new methods for the diagnosis of pneumonia. Prevention strategies should focus on more effective infection control techniques, improved invasive devices/equipment, and the judicious use of antibiotics for treatment and prophylaxis. PMID- 1928192 TI - Surgical wound infection. AB - Wound infections remain a major source of postoperative morbidity, accounting for about a quarter of the total number of nosocomial infections. Today, many of these infections are first recognized in the outpatient clinic or in the patient's home due to the large number of operations done in the outpatient setting. This leads to errors in establishing the true incidence of their occurrence but undoubtedly decreases the overall real cost and length of hospital stay. The pathogens implicated in the development of wound infections remain largely the human microorganisms from the exogenous environment and the endogenous organ microflora. Many perioperative factors have been identified that increase the incidence of the development of postoperative wound infection. Avoidance of these factors as well as the appropriate use of perioperative antibiotic prophylaxis has decreased the incidence of wound infection. During the last decade many studies have reported on the individual risk factors that favor the development of postoperative infectious complications in various surgical procedures. It is hoped that this knowledge may allow for prospective alterations in the preventative and therapeutic modalities in the high-risk patient in the studies designed in the 1990s. The use of effective infection surveillance both in the hospital and in the outpatient setting is mandatory in order to collect meaningful data. The use of computer technology will greatly facilitate the proper surveillance, analysis, and control of infections in the surgical patient. PMID- 1928193 TI - The Third Decennial International Conference on Nosocomial Infections. Historical perspective: the landmark conference in 1980. PMID- 1928194 TI - Catheter-associated urinary tract infections: epidemiology, pathogenesis, and prevention. AB - Catheter-associated urinary tract infections (UTIc) remain the most common nosocomial infection. Although usually benign, UTIc cause bacteremia in 2-4% of patients and have been associated with a case fatality rate three times as high as nonbacteriuric patients. Risk factors for UTIc identified in multivariate analyses include increasing duration of use, female sex, absence of systemic antibiotics, and disconnection of the catheter-collecting tube junction. Recent studies suggest that most episodes of low colony count bacteriuria (10(2)-10(4) cfu/ml) rapidly progress to high (greater than or equal to 10(5)/ml) colony counts within 24-48 hours. In persons with long-term catheterization, bacteriuria inevitably develops and the infecting strains change frequently. In this setting, Proteus and Morganella species produce catheter encrustations and persistent bacteriuria. Routes of bacterial entry have been well defined and differ by gender, with the periurethral route predominating in women and the intraluminal route in men. Growth of bacteria in biofilms on the inner surface of catheters promotes encrustation and may protect bacteria from antimicrobial agents. Bacterial virulence factors have not been well characterized in UTIc, but fimbrial adhesins have been associated with bacterial persistence in the catheterized urinary tract, and urease production has been associated with stone formation and catheter encrustation. Recent efforts to prevent UTIc have focused mainly on preventing bacterial entry to the urinary tract or eradicating bacteriuria after its onset and have been largely unsuccessful. Systemic antimicrobials, sealed tubing and catheter junctions, silver ion-coated catheters, and antiseptics in the collecting bag have all been efficacious in one or more controlled trials. Failure to stratify patients by major risk factors, especially gender, antimicrobial exposure, and catheter duration, makes interpretation of many trials difficult. Further research in the areas of innovative catheter system design, bacterial-host epithelial cell interaction, and targeted antimicrobial prophylaxis seem the most likely approaches to controlling UTIc in the future. PMID- 1928195 TI - Major trends in the microbial etiology of nosocomial infection. AB - To determine trends in the microbial etiology of nosocomial infections in the 1980s, surveillance data on the microbiology of documented nosocomial infection reported to the National Nosocomial Infections Surveillance System and from the University of Michigan Hospital were analyzed. Antimicrobial susceptibility data on selected pathogens from both sources were also reviewed. Overall, Escherichia coli decreased from 23% of infections in 1980 to 16% in 1986-1989, Klebsiella pneumoniae dropped from 7% to 5%, whereas coagulase negative staphylococci increased from 4% to 9% and Candida albicans increased from 2% to 5%. Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter species and enterococci had minor increases, but antimicrobial resistant strains for these pathogens as well as coagulase-negative staphylococci were seen more frequently. In contrast to the 1970s, major shifts in the etiology of nosocomial infection have occurred in the decade of the 1980s. Taken as a whole, the shifts are away from more easily treated pathogens toward more resistant pathogens with fewer options for therapy. These shifts underscore the continued need for prevention and control to accompany new developments in therapy. PMID- 1928196 TI - Contemporary challenges for hospital epidemiology. AB - According to conventional wisdom, it is time for hospital epidemiologists to look beyond traditional infection control responsibilities and to shoulder an "expanded role," including quality assurance, risk management, and pharmacoepidemiology. Some see this as a matter of survival as the profession reacts to potent external forces that seek to curb the cost of health care while assuring quality service. Infection control specialists, it is argued, have the epidemiologic skills to measure adverse outcomes of hospitalization, adjust for confounding variables, and evaluate the impact of targeted interventions. Before embracing these new responsibilities, however, it should be noted that many hospital epidemiologists would require additional training in basic epidemiologic principles. Although hospital epidemiologists may seek a leadership role in hospital quality assurance and health policy research, they have generally not been innovators in these fields, even in some specific areas relevant to infection control. For example, while hospital epidemiologists have begun to consider severity of illness as a potential confounder in epidemiologic analyses, they have not participated in the development or validation of any of the most widely used indicators. For those hospital epidemiologists who wish to capitalize on their traditional background in infectious diseases, contemporary infection control provides numerous challenges. For example, the epidemiology of many common nosocomial infections, such as bacterial pneumonia in immunocompromised hosts, remains to be defined. Hospital epidemiologists need to incorporate a variety of sophisticated microbiologic methods into their practice to help them trace the spread of nosocomial pathogens. Finally, they should collaborate more closely with clinical and bench investigators in a number of areas, including microbial pathogenesis, immunology, and biotechnology. PMID- 1928197 TI - Secular trends in nosocomial primary bloodstream infections in the United States, 1980-1989. National Nosocomial Infections Surveillance System. AB - More than 25,000 primary bloodstream infections (BSIs) were identified by 124 National Nosocomial Infections Surveillance System hospitals performing hospital wide surveillance during the 10-year period 1980-1989. These hospitals reported 6,729 hospital-months of data, during which time approximately 9 million patients were discharged. BSI rates by hospital stratum (based on bed size and teaching affiliation) and pathogen groups were calculated. In 1989, the overall BSI rates for small (less than 200 beds) nonteaching, large nonteaching, small (less than 500 beds) teaching, and large teaching hospitals were 1.3, 2.5, 3.8, and 6.5 BSIs per 1,000 discharges, respectively. Over the period 1980-1989, significant increases (p less than 0.0001) were observed within each hospital stratum, in the overall BSI rate and the BSI rate due to each of the following pathogen groups: coagulase-negative staphylococci, Staphylococcus aureus, enterococci, and Candida species. In contrast, the BSI rate due to gram-negative bacilli remained stable over the decade, in all strata. Except for small nonteaching hospitals, the greatest increase in BSI rates was observed in coagulase-negative staphylococci (the percentage increase ranged between 424% and 754%), followed by Candida species (219-487%). In small nonteaching hospitals, the greatest increase was for S. aureus (283%), followed by enterococci (169%) and coagulase-negative staphylococci (161%). Our analysis documents the emergence over the last decade of coagulase-negative staphylococci as one of the most frequently occurring pathogens in BSI. PMID- 1928198 TI - Temporal trends in septicemia in a community hospital. AB - A prior study of septicemia in our community teaching hospital demonstrated the importance of case mix categories in understanding differences in rates of septicemia seen in hospitals. This study provides a 10 year, in 1982, and a 15 year, in 1987, follow-up of septicemia from the same hospital. A substantial increase in the incidence of septicemia was noted in 1982 and 1987. Underlying illness categories continued to be important predictors of incidence of septicemia and fatality rates. The sites of infections, relative mix of community acquired and nosocomial infections, and mix of organisms were fairly stable throughout the period. The overall incidence of septicemia increased from 34/10,000 admissions in 1970-1973 to 87/10,000 in 1982 and 103/10,000 in 1987. The major explanations for these increases are: (a) a striking increase in the use of blood cultures from 1 blood culture per 10.4 patients in 1973 to 1 blood culture per 3.3 patients in 1987; (b) an increase in the proportion of patients in the Medicare age group from 13% in 1970-1973 to 24% in 1987, with that age group accounting for 33% of the cases of septicemia in 1970-1973 and 55% in 1982 and 1987; and (c) a modest change in the case mix category of ultimately fatal underlying illness and a probable increase in the acuity of illness for most patients admitted. Parallel changes in frequency of use of blood cultures have occurred at the previously evaluated medical school teaching hospital in the same community. These same explanations are likely to be applicable for the same time period in other acute care hospitals as well. PMID- 1928199 TI - Infectious complications among patients receiving home intravenous therapy with peripheral, central, or peripherally placed central venous catheters. AB - Rates of bacteremia among hospitalized patients with central venous catheters range up to 21%. Few data exist for home intravenous therapy (IVT). We studied 300 patients from two hospital-based home IVT services in 29 months. Diagnoses included 92 cases of osteomyelitis, 33 of pneumonia, 35 of malnutrition, 26 of chronic pain, and 114 of other diseases. Peripheral IVT was given to 97 patients. Mean age was 39.4 years (range, 0.3-98). Hickman, Infuse-A-Port, Broviac, Arrow triple lumen, Hohn, and peripherally inserted central catheters (PICC) were used for a mean of 44 days. Six bacteremias (one death) (2%, 4.6/10,000 catheter days), two subclavian thromboses, 13 catheter site infections, and one additional death occurred. PICC experience included 76 patients, mean age 46 years (range, 4 76), primarily with infections, chronic pain, or dehydration. Mean duration of therapy was 24 days (0-67) and was completed in 51 patients; others completed therapy with standard peripheral catheters a mean of 6 days later. Complications included 17 obstructions by clot, 11 cases of phlebitis, six catheter fractures, five punctures, two accidental removals, and one infiltration. Liquid silicone repaired holes; urokinase opened clots. Successful completion of therapy was more common in the second year, 88% versus 57%. Despite more complications, patients, home IVT nurses, and physicians preferred PICCs. We conclude that home IVT is safe via many means of access, with fewer infections than with hospital care. Such infections may be termed "nosohusial." PMID- 1928200 TI - Interactions between organic nitrates and thiol groups. AB - Nitroglycerin and the organic nitrates (RONO2) can be considered prodrugs that require conversion to an active intracellular moiety that initiates vascular smooth muscle relaxation. Vasodilation of veins and arteries occurs when the enzyme guanylate cyclase (GC) is activated, initiating the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP); this is the final pathway for vascular dilation caused by the nitrovasodilators (organic nitrates, sodium nitroprusside, and molsidomine) as well as endothelium-derived relaxing factor (EDRF). The common denominator appears to be the intracellular production of nitric oxide (NO), which is the activated product of organic nitrate denitration. Nitrate tolerance has been associated with a relative depletion or unavailability of thiol groups that are involved in the initial step of denitration of RONO2. Sulfhydryl groups (SH) are oxidized during this process; with continuous nitrate exposure, decreased nitrate metabolism within the vascular smooth muscle cell occurs as a direct result of the depletion of reduced SH groups. Thus, less NO is formed and cGMP production is diminished, with a subsequent decrease or absence of vasodilation. In addition, SH groups or thiols are required for the production of S-nitrosothiols (RSNO). These short-lived compounds have been identified as an end product of organic nitrate metabolism and as possibly obligatory for the induction of GC. It is unclear, however, as to whether S-nitrosothiols are a necessary by-product of NO production from organic nitrates. It appears that RSNO can be formed outside the cell membrane and may be able to induce vasorelaxation after penetrating the cell and initiating GC activation. Exogenous SH donors, particularly N-acetylcysteine (NAC), have been employed to provide intracellular thiols in efforts to prevent or reverse nitrate tolerance. Nitrate physiologic actions are accentuated following NAC administration in the absence of tolerance. Although controversial, the concept that NAC or other thiols might be able to prevent the development of nitrate tolerance is being actively studied in laboratories around the world. Methionine has also been utilized as an SH donor with some success. Not all data are consistent, however, and the ultimate role of thiol donors for the prevention or reversal of nitrate tolerance remains uncertain. Finally, there has been considerable interest in supplying thiols by use of the SH-containing angiotensin converting enzyme inhibitors, such as captopril. This approach does not seem promising, probably because insufficient thiol can be supplied by therapeutic dosages of these drugs. PMID- 1928201 TI - Thiol-containing agents in the management of unstable angina pectoris and acute myocardial infarction. AB - The development of unstable angina pectoris and acute myocardial infarction is a process of platelet aggregation and thrombus formation associated with local coronary vasoconstriction. Regional deficiencies in endothelial vasodilator function, due to reduced formation of endothelium-derived relaxing factor (EDRF), may predispose to platelet aggregation and coronary vasoconstriction. Nitroglycerin (NTG), frequently utilized in the management of unstable angina pectoris and acute myocardial infarction, undergoes bioconversion, via a sulfhydryl-dependent process, to nitric oxide, which is identical or closely related to EDRF. Other products of the nitrate bioconversion "cascade" are various S-nitrosothiols, which, like nitric oxide, activate soluble guanylate cyclase, inducing increased formation of cyclic guanosine monophosphate. NTG potentially may act to correct a localized deficiency of EDRF effect, at both the vasculature and platelet levels. In patients with unstable angina, hemodynamic effects and therapeutic efficacy of intravenously infused NTG may be attenuated within hours. Combined therapy with NTG and intravenously infused N acetylcysteine (NAC) results in potentiation of hemodynamic responses to NTG, markedly augments the effects of NTG on platelet aggregation, and reduces the incidence of acute myocardial infarction in patients with severe unstable angina pectoris. The combination of NTG with intermittent NAC infusion may increase the risk of hypotensive episodes in such patients, whereas continuous coinfusion of the drugs is better tolerated. The combination of NTG with thiol-containing agents, such as NAC, may be of therapeutic value in unstable angina pectoris and in evolving acute myocardial infarction. This is currently under investigation. PMID- 1928202 TI - Prospects for antioxidant therapy in cardiovascular medicine. PMID- 1928203 TI - Antioxidant activity and other mechanisms of thiols involved in chemoprevention of mutation and cancer. AB - Our studies provide evidence that thiols, such as N-acetyl-L-cysteine, inhibit both spontaneous mutations and induced mutations in bacteria, prevent the in vivo formation of carcinogen-DNA adducts, and suppress or delay the development of tumors or preneoplastic lesions in rodents. N-Acetylcysteine and other thiols exert antioxidant activity toward superoxide anion, hydrogen peroxide, and singlet oxygen, assessed in bacterial genotoxicity models. In addition, several other mechanisms were shown to contribute to their antimutagenic and anticarcinogenic activities, in the extracellular environment and in nontarget or target cells. These mechanisms include blocking of electrophilic metabolites and of direct-acting compounds, either of endogenous or exogenous source, modulation of several xenobiotic-metabolizing pathways, and protection of DNA-dependent nuclear enzymes. Chemoprevention of mutation and cancer by thiols is particularly useful under conditions of reduced glutathione (GSH) depletion due to toxic agents or to cancer-associated viral diseases, such as acquired immunodeficiency syndrome (AIDS) or viral hepatitis B. PMID- 1928204 TI - Use of N-acetylcysteine in clinical toxicology. AB - The major use of N-acetylcysteine in clinical toxicology is in the treatment of acetaminophen (paracetamol) overdosage. The hepatorenal toxicity of acetaminophen is mediated by a reactive metabolite normally detoxified by reduced glutathione. If glutathione is depleted, covalent binding to macromolecules and/or oxidation of thiol enzymes can lead to cell death. Oral or intravenous N-acetylcysteine or oral D,L-methionine mitigates acetaminophen-induced hepatorenal damage if given within 10 hours, but becomes less effective thereafter. In vivo, N-acetylcysteine forms L-cysteine, cystine, L-methionine, glutathione, and mixed disulfides; L methionine also forms cysteine, thus giving rise to glutathione and other products. Oral therapy with N-acetylcysteine or methionine for acetaminophen poisoning is contraindicated in the presence of coma or vomiting, or if activated charcoal has been given by mouth. Nausea, vomiting, and diarrhea may also occur as a result of oral N-acetylcysteine administration. Anaphylactoid reactions including angioedema, bronchospasm, flushing, hypotension, nausea/vomiting, rash, tachycardia, and respiratory distress may occur 15-60 minutes into N acetylcysteine infusion (20 hours intravenous regimen) in up to 10% of patients. Following accidental intravenous overdosage, the adverse reactions of N acetylcysteine are similar but more severe; fatalities have occurred. A reduction in the loading dose of N-acetylcysteine may reduce the risk of adverse reactions while maintaining efficacy. Administration of N-acetylcysteine for a longer period might provide enhanced protection for patients in whom acetaminophen absorption or elimination is delayed. N-acetylcysteine may also have a role in the treatment of toxicity from carbon tetrachloride, chloroform, 1,2 dichloropropane, and other compounds. The possible use of N-acetylcysteine and other agents in the prevention of the neuropsychiatric sequelae of acute carbon monoxide poisoning is an important area for future research. PMID- 1928205 TI - Reactive oxygen species in living systems: source, biochemistry, and role in human disease. AB - Reactive oxygen species are constantly formed in the human body and removed by antioxidant defenses. An antioxidant is a substance that, when present at low concentrations compared to that of an oxidizable substrate, significantly delays or prevents oxidation of that substrate. Antioxidants can act by scavenging biologically important reactive oxygen species (O2-., H2O2.OH, HOCl, ferryl, peroxyl, and alkyl), by preventing their formation, or by repairing the damage that they do. One problem with scavenging-type antioxidants is that secondary radicals derived from them can often themselves do biologic damage. These various principles will be illustrated by considering several thiol compounds. PMID- 1928206 TI - Modulation of lymphocyte functions and immune responses by cysteine and cysteine derivatives. AB - Mitogenically stimulated human peripheral blood lymphocytes and T cell clones were found to have weak membrane transport activity for the disulfide cystine but strong membrane transport activity for the thiol amino acid cysteine. Cysteine, however, is represented at the lowest concentration among all protein-forming amino acids in the blood plasma. Complementary laboratory experiments have shown that the cysteine supply is indeed limiting for important lymphocyte functions. Proliferative responses of mitogenically stimulated lymphocytes and T-cell clones and the activation of cytotoxic T cells in allogeneic mixed lymphocyte cultures are strongly influenced by small variations in the extracellular cysteine concentration even in the presence of relatively high and approximately physiologic concentrations of cystine. Cysteine can be substituted by N acetylcysteine but not by cystine. The more detailed analysis revealed that the extracellular supply of cysteine influences strongly the intracellular level of glutathione (GSH) and also the activity of the transcription factor NF kappa B that regulates the expression of several immunologically relevant genes. In vitro experiments including double-chamber experiments with macrophages and lymphocytes revealed, moreover, that cysteine plays an important role as a regulatory mediator between these cell types. The cysteine supply is impaired directly or indirectly in several pathologic conditions that are associated with immunodeficiencies, including the acquired immune deficiency syndrome (AIDS). Cysteine or cysteine derivatives may therefore be considered for the treatment of patients with HIV-1 infection. PMID- 1928207 TI - Oxidants and antioxidants: state of the art. AB - Reactive oxygen species are regarded as merely pernicious. This is incorrect for they play a pivotal role in many physiologic reactions, such as cytochrome P450 mediated oxidations, regulation of the tone of smooth muscle, and killing of microorganisms. An imbalance in oxidant-antioxidant activity is involved in many free radical-mediated pathologies, e.g., ischemia-reperfusion and asthma. In an attempt to alleviate these pathologies with antioxidants, it should be noted that these compounds are neither specific nor mere antioxidants. Associated with antioxidant activity is a pro-oxidant action. In the development of new antioxidant therapies, the important question of how these drugs are incorporated in or commensurate with existing integrated physiologic radical-defense systems should be addressed. PMID- 1928208 TI - Cellular injury by oxidants. AB - Oxidants, generated by stimulated leukocytes, induce a variety of distinct biochemical changes in target cells. Hypochlorous acid (HOCl), produced by the action of peroxidase on hydrogen peroxide (H2O2) in the presence of chloride ions, acts at low molar concentrations (10-20 microM) to damage proteins on cell membranes and destroy their function. H2O2 rapidly permeates cells and causes inhibition of adenosine triphosphate (ATP) synthesis via both glycolytic and oxidative phosphorylation (mitochondrial) pathways. In the glycolytic pathway, damage is limited to the step involving glyceraldehyde-3-PO4 dehydrogenase (GAPDH). This results from both an attack of H2O2 on GAPDH and, indirectly, by a reduction in concentration of the GAPDH cofactor, nicotinamide adenine dinucleotide (NAD). This latter effect was found to result from activation of the enzyme, poly(adenosine diphosphate) (ADP)-ribose polymerase, an enzyme involved in deoxyribonucleic acid (DNA) repair. DNA damage in target cells was found at low concentrations of H2O2 (20-80 microM) in many cell types. Strand breaks and base hydroxylation were observed, resulting in the generation of hydroxyl radicals (.OH) from H2O2, in the presence of a transition metal. DNA damage resulted in either cell injury and death or mutations of the base sequence and amino acid residues. These latter effects led to malignant transformations in cultured cells in both tissue cultures of the cells, and in vivo in athymic mice. Exposure of a proto-oncogene, K-ras 4B, also led to the development of a malignant transformation by virtue of mutations in codon positions 12 and 61. Thus, oxidant effects on target cells can damage multiple functional pathways inside the cells, as well as give rise to malignant transformation via DNA damage. PMID- 1928209 TI - Oxidative stress: from basic research to clinical application. AB - The occurrence of reactive oxygen species, known as pro-oxidants, is an attribute of normal aerobic life. The steady-state formation of pro-oxidants is balanced by a similar rate of their consumption by antioxidants that are enzymatic and/or nonenzymatic. "Oxidative stress" results from imbalance in this pro-oxidant antioxidant equilibrium in favor of the pro-oxidants. A number of diseases are associated with oxidative stress, being the basis of antioxidant therapy. Current evidence in clinical research does not show unequivocal distinction between causal or associative relationships of pro-oxidants to the disease process. PMID- 1928210 TI - Oxidants and respiratory tract epithelial injury: pathogenesis and strategies for therapeutic intervention. PMID- 1928211 TI - Oxidant-antioxidant balance: some observations from studies of ischemia reperfusion in isolated perfused rat hearts. AB - Alteration in oxidant-antioxidant balance is a key feature of many common vascular diseases. Using an isolated perfused heart model, we found that (a) xanthine oxidase-derived oxygen radicals contributed to ischemia-reperfusion injury; (b) addition of antioxidants within or outside erythrocytes decreased injury following ischemia-reperfusion; (c) endotoxin pretreatment increased myocardial catalase activity and decreased injury following ischemia-reperfusion; (d) interleukin pretreatment increased myocardial glucose-6-phosphate activity and decreased ischemia-reperfusion injury, and (e) neutrophils mediated tolerance to a subsequent oxidative stress by causing a small oxidant stress that in turn increased antioxidant protection mechanisms. PMID- 1928212 TI - N-acetylcysteine in experimental and clinical acute lung injury. AB - Clinically, lung injury is characterized by one or more of the following: altered gas exchange, dyspnea, decreased static compliance, and nonhydrostatic pulmonary edema. Although many antioxidants have been investigated in in vitro systems and in animal models, only some are at the developmental stage, or safe for clinical trials. Considerable evidence has recently accumulated supporting the hypothesis that leukocyte activation involves release of large quantities of highly reactive oxygen radicals, and hydrogen peroxide is partially responsible for diffuse microvascular and tissue injury in septic patients. Granulocyte depletion in animal models reduces the degree of fall in dynamic lung compliance and the increase in airflow resistance, lymph flow, and hypoxemia secondary to endotoxin administration. We hypothesized that the partial benefit derived from granulocyte depletion was due to the effective removal of a major source of oxygen radicals. Among the list of free radical scavengers, N-acetylcysteine stands out, because of its established usefulness in at least one human disease thought to be secondary to free radical organ damage (acetaminophen or paracetamol overdose). It is an extremely safe agent with a wide toxic-therapeutic window. An increasing number of animal studies indicate efficacy for this agent in the prevention and therapy of lung injury involving toxic oxygen species. We developed a randomized, double-blind protocol for the study of intravenous N-acetylcysteine in patients with established adult respiratory distress syndrome (ADRS). Results of this trial are preliminary. Nevertheless, they indicate that plasma and red cell glutathione levels are decreased in ADRS patients, and that N-acetylcysteine increases plasma cysteine as well as plasma and red cell glutathione. There are also indications that cardiopulmonary physiology is favorably affected by such therapy including improvements in chest radiograph edema scores, pulmonary vascular resistance, static compliance, oxygen delivery, and oxygen consumption. PMID- 1928213 TI - The effects of N-acetylcysteine and glutathione on smoke-induced changes in lung phagocytes and epithelial cells. AB - We studied the mechanism of the delay in neutrophil traffic in pulmonary microvasculature previously observed during cigarette smoking, the effect of cigarette smoke on lung phagocytes and epithelial cell function, and augmentation of the glutathione (GSH) antioxidant system using the thiol drug N acetylcysteine. Using a micropore membrane system to mimic the dimensions of the average pulmonary capillary, we showed that cigarette smoke reduces cell deformability, increasing the difficulty experienced by the larger neutrophils in negotiating the smaller capillary segments, so delaying their passage during smoking. This effect is both diminished and recoverable by the addition of plasma, and by GSH in concentrations found in plasma. Cigarette smoke induces oxidative changes in both the cell membrane and the cell cytoskeleton, and diminishes the ability of neutrophils to release reactive oxygen intermediates. The injurious effect of oxidants can be measured in vitro by the detachment of 51Cr-radiolabeled alveolar epithelial cells grown in monolayers, an effect also diminished by the addition of GSH. Such epithelial cell detachment in vitro may be reflected as the epithelial permeability that occurs at an early stage in asymptomatic smokers. N-Acetylcysteine given orally (600 mg/day) increases both plasma and bronchoalveolar lavage GSH in normal subjects, but a sustained increase in plasma GSH requires higher dosage regimens in patients with chronic obstructive pulmonary disease (600 mg three times daily). Thus, the potential exists to enhance the antioxidant status of both plasma and the airspaces of the lungs against oxidant-induced injury. PMID- 1928214 TI - Ozone-induced impairment of mucociliary transport and its prevention with N acetylcysteine. AB - The effects of an oxidizing gaseous pollutant on tracheal mucous velocity have been studied in conscious sheep. Acute (2 hours) exposure to 1.0 ppm of ozone showed an effect on tracheal mucous velocity that resulted in a significant decrease 40 minutes and 2 hours after exposure (35% and 40% of the baseline, respectively). Repeated exposure for longer periods (4 days, 5 hours/day) to 1.0 ppm of ozone also significantly decreased tracheal mucous velocity during the first and the second day (-47% and -70% of the baseline, respectively), but during the following days of exposure adaptation took place (tracheal mucous velocity ranging from -42% to -55% of baseline). The tracheal mucous velocity still significantly decreased 5 days after the last exposure. N-Acetylcysteine, known both for its mucolytic and antioxidizing properties, has been demonstrated to prevent significantly all of the immediate effects of either short-term or long-term ozone exposures on mucociliary functions. PMID- 1928215 TI - Oxidative metabolism of circulating granulocytes in adult respiratory distress syndrome. AB - Among the different mechanisms involved, polymorphonuclear leukocytes (PMNs) may play a central role in the pathogenesis of adult respiratory distress syndrome (ARDS). PMNs were evaluated in 15 patients with ARDS, in 21 at risk of developing ARDS (AR), and in 36 controls (C). Spontaneous and opsonized zymosan (OZ), phorbol myristate acetate (PMA), and F-Met-Leu-Phe (F-M-L-P)-stimulated oxygen radical production was measured by luminol- and lucigenin-enhanced chemiluminescence (CL). Spontaneous CL activity of PMNs from ARDS patients was significantly greater than that from the PMN control (luminol CL, 2.8 +/- 0.6 vs. 0.8 +/- 0.1 mV, p less than 0.001; lucigenin CL, 2.0 +/- 0.6 vs. 0.30 +/- 0.04 mV, p less than 0.001), and the CL value from AR patients (luminol CL, 1.3 +/- 0.2 mV, p less than 0.001 vs. C; lucigenin CL, 0.8 +/- 0.1 mV, p less than 0.001 vs. C) was found to be between the ARDS and C patients. The peak of PMA stimulated CL occurred earlier and it was significantly higher in ARDS patients than in AR patients (p less than 0.05) and controls (p less than 0.001). When the CL response was elicited with F-M-L-P, no difference among the three groups was found. When stimulated with OZ, the peak CL generated by PMNs from ARDS patients was significantly depressed compared with controls (luminol CL, 26.7 +/- 1.8 vs. 40.9 +/- 2.3 mV, p less than 0.01; lucigenin CL, 5.0 +/- 0.4 vs. 7.4 +/- 0.5 mV, p less than 0.005) with a similar result being obtained from AR patients (luminol CL, 32.1 +/- 2.5 mV, p less than 0.01 vs. C). Plasma from ARDS and AR patients showed a defective opsonizing capacity, suggesting in vivo complement consumption in both patient groups. No correlation between the severity of hypoxemia, the cause of ARDS, the outcome, and the different PMN functions could be established. Our results are in agreement with a determinant role of PMNs in the development of ARDS. The opposite metabolic responses may explain both the pulmonary injury and the increased susceptibility to infections observed in patients at risk of or with ARDS. PMID- 1928216 TI - Myocardial injury mediated by oxygen free radicals. AB - Increasing evidence suggests that oxygen free radicals play a major role in the pathogenesis of reperfusion injury. Initial indirect evidence was based on beneficial effects of free radical scavengers administered exogenously at the time of postischemic reperfusion. Recent electron paramagnetic resonance (EPR) spectroscopy studies show a burst of oxygen-centered free radical generation during the first 60 seconds of reflow and administration of either a free radical scavenger, such as superoxide dismutase (SOD), or an iron chelator, such as deferoxamine, prevents this burst. The in vitro data obtained in a perfused rabbit heart model and the impressive reduction in infarct size, shown in an intact canine model, suggest that well-designed, randomized, placebo-controlled clinical trials of free radical scavengers and/or antioxidants should be performed to determine if postischemic reperfusion injury can be shown and/or prevented in humans. PMID- 1928217 TI - Myocardial reperfusion injury: mechanisms and management--a review. PMID- 1928218 TI - Mechanisms of endothelial cell killing by H2O2 or products of activated neutrophils. AB - Interactions between rat pulmonary artery endothelial cells and hydrogen peroxide or toxic oxygen products from phorbol ester-activated human neutrophils result in endothelial cell killing defined by 51Cr release. It has been shown that this cytotoxic reaction can be blocked by the presence of catalase, iron chelators, or scavengers of the hydroxyl radical. Evidence shows that products from xanthine oxidase of endothelial cells are necessary for the toxic effects of hydrogen peroxide or phorbol ester-activated neutrophils. Addition of xanthine oxidase inhibitors protects against phorbol ester-mediated injury of endothelial cells. Preloading of endothelial cells with superoxide dismutase attenuates injury caused either by hydrogen peroxide or phorbol ester-activated neutrophils. Conversion of xanthine dehydrogenase to xanthine oxidase in endothelial cells occurs during contact of endothelial cells by activated neutrophils. This conversion is not related to oxygen products of neutrophils. Conversion of xanthine dehydrogenase to xanthine oxidase in endothelial cells is also induced by endothelial cell contact with C5a, N'-formyl-methionyl-leucyl-phenylalanine (fMLP), or tumor necrosis factor alpha (TNF alpha). Interaction of hydrogen peroxide with endothelial cells rapidly depletes adenosine triphosphate (ATP) and causes the extracellular appearance of xanthine and hypoxanthine. Agents that protect endothelial cells from the toxic effects of hydrogen peroxide do not prevent falls in cellular ATP caused by hydrogen peroxide, indicating that ATP levels do not necessarily correlate with cytotoxic events. A synergy between hydrogen peroxide and proteases in endothelial cell killing has been demonstrated. TNF alpha causes alterations in endothelial cells, the result of which is increased susceptibility to killing by PMA-activated neutrophils. PMID- 1928219 TI - Oxygen free radicals and myocardial damage: protective role of thiol-containing agents. AB - It has been suggested that the sudden presence of oxygen during reperfusion after a period of ischemia may be toxic for the myocardial cell. The oxygen molecule is capable of producing reactions in the cell, forming highly reactive free radicals, and inducing lipid peroxidation of membranes, altering their integrity and increasing their fluidity and permeability. The ischemic and reperfused cardiac cell is the prime candidate for this reaction sequence and may explain the molecular mechanism underlying the pathologic events related to membrane dysfunction and calcium homeostasis. However, the myocardium has a series of defense mechanisms including the enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase plus other endogenous antioxidants such as vitamin E, ascorbic acid, and cysteine to protect the cell against the cytotoxic oxygen metabolites. The prerequisite for oxygen free radical involvement in ischemia and reperfusion damage is that ischemia alters the defense mechanisms against oxygen toxicity. It is known that ischemia may impair mitochondrial SOD and, with reperfusion, oxidative stress may occur as shown by tissue accumulation and release of oxidized glutathione. This tripeptide molecule in the cofactor of glutathione peroxidase, the enzyme that removes hydrogen and lipid peroxides. Its formation and subsequent release is a reliable index of oxidative damage. In our study, we investigated the effects of N-acetylcysteine on oxidative damage in the isolated rabbit heart. N-acetylcysteine increases, in a dose-dependent manner (from 10(-7) to 10(-5) M), the myocardial glutathione content and provides an important degree of protection against ischemia and reperfusion. Oxidative stress does not occur, mitochondrial function is maintained, enzyme release is reduced, and contractile recovery is increased. Similarly, we administered N acetylcysteine in the pulmonary artery of coronary artery disease patients undergoing coronary bypass grafting (150 mg/kg in 1 hour followed by 150 mg/kg in 4 hours). The degree of oxidative stress on reperfusion was reduced and recovery of cardiac function improved. In this article, we review the cardioprotective role of thiol-containing agents. PMID- 1928220 TI - Ten weeks of intermittent hypocalcemic stimulation does not produce functional parathyroid hyperplasia. AB - Hypocalcemia is a major stimulus for parathyroid hormone secretion and presumably the major cause of parathyroid hyperplasia in chronic hypocalcemic syndromes. We could find no data to indicate what degree, duration, or frequency of hypocalcemia is needed to produce parathyroid hyperplasia in humans. We have monitored the effects of thrice weekly hypocalcemic parathyroid stimulation for 10 weeks. Measurements were made during a study designed to test the feasibility of carrying out a randomized, blinded trial of "chelation therapy," a widely used but unproven method to treat atherosclerotic symptoms. Eight patients received infusions of disodium ethylenediaminetetraacetic acid (EDTA) and six received placebo infusions thrice weekly for ten weeks. The EDTA infusions (50 mg/kg over three hours) lowered serum ionized calcium at two hours by an average of 0.20 mmol/L and trebled the immunoreactive parathyroid hormone (iPTH) value. Basal serum iPTH, ionized calcium and 1,25-dihydroxyvitamin D values, measured just before the infusion, did not change significantly after 10 weeks of treatment with either EDTA or placebo. The increment in serum iPTH produced by the EDTA induced hypocalcemia was also unchanged. Lowering ionized serum calcium to values below the normal range three times a week for 10 weeks is not a sufficient stimulus to cause a detectable increase in basal or stimulated parathyroid function. PMID- 1928222 TI - Enhanced neutrophil function in children on bromide therapy. AB - The final step in neutrophil bacterial killing is formation of a toxic halide complex. For this reason, we studied neutrophil function in children receiving bromide anticonvulsant therapy. Whole blood and serum were obtained from 7 patients with seizure disorders treated orally with triple bromide elixir to examine neutrophil function as measured by luminol enhanced chemiluminescence (CL). Serum bromide concentrations [Br-] were determined concomitantly. There was a direct correlation between [Br-] and CL activity of neutrophils (r = 0.87) with peak CL responses significantly higher than controls when [Br-] were in the therapeutic range (10-20 mM). With [Br-] above 25 mM, CL activity was reduced. Serum from patients also enhanced CL of control neutrophils with a similar relationship to measured [Br-]. To confirm that enhanced neutrophil activity was attributable to [Br-] use, [Br-] ranging from 0-50 mM were added to control neutrophils in otherwise normal physiologic conditions and the CL assay was performed. Results expressed as percent of control values were as follows: [Br-] 5 mM, 110%; 10 mM, 158%; 15 mM, 194%; 20 mM, 252%; 25 mM, 136%; 30 mM, 364%; and 50 mM, 205%. These data demonstrate that Br- enhances phagocytic and bactericidal activity of neutrophils and suggest that Br- therapy may augment host defense capabilities. PMID- 1928221 TI - A CF-lectin factor in amniotic fluid from pregnancies at risk for cystic fibrosis. AB - A method was developed for the assay of the CF-lectin factor in amniotic fluid using samples from fetuses identified by other means as having or not having cystic fibrosis (CF). The method involves protein removal from the amniotic fluid by filtration through Centricon-10 Amicon filters, admixture of filtrate with normal serum as a source of IgM, and incubation in 5% Dextran-Sulfate with mouse red blood cells to detect specific hemagglutination. Blind samples submitted from four different laboratories were used to evaluate the ability of the assay to differentiate CF fetuses from fetuses without CF. Storage of samples from one laboratory had been quite prolonged and was associated with poor correlations. Freezing and thawing of samples were shown to deactivate the CF-lectin factor. In three of the four studies, CF lectin was detected in 77% of pregnancies identified as CF at birth, prenatally through microvillar enzyme assay or through DNA analysis of terminated pregnancies. Eighty-three percent of samples identified as normal were confirmed as such by a lack of CF-lectin activity. These data suggest that CF fetuses produce, and are exposed to, the CF-lectin factor at least as early as the second trimester of gestation. PMID- 1928223 TI - The bronchodilator terbutaline enhances digitalis-induced arrhythmia. AB - The hypothesis that beta 2-sympathomimetics augment digitalis-induced arrhythmias and antagonize its positive inotropic action was tested in isolated, electrically driven guinea-pig left atria. Alone, 0.3 mM terbutaline enhanced myocardial force generation but did not induce dysrhythmia. Terbutaline shortened the time to the onset of 3 microM ouabain-induced arrhythmia by approximately 75% from 19.7 +/- 3.2 minutes to 5.7 +/- 1.2 minutes (p less than 0.005). The enhancement of arrhythmias appeared to be the result of triggering ouabain-induced delayed afterdepolarizations (DAD) into overt arrhythmia. The effect of terbutaline was antagonized by blocking cardiac beta-adrenoceptors with propranolol. Terbutaline did not affect the ability of ouabain to increase myocardial contractility. PMID- 1928224 TI - Case report: fatal pulmonary toxoplasmosis following chemotherapy. AB - A 41-year-old woman with acute myelomonocytic leukemia in remission died of a rapidly progressive necrotizing pneumonia while in the recovery phase following consolidation chemotherapy. Autopsy revealed disseminated toxoplasmosis. Although this syndrome has been well described to present as a neurologic complication in certain immunocompromised patients, it is rare in acute leukemia, and non neurologic presentations are even more unusual. This case emphasizes the need to be suspicious of toxoplasmosis in immunocompromised patients even in the absence of neurologic signs or symptoms. PMID- 1928225 TI - Case report: Chlamydia pneumoniae pneumonia in an HIV-infected man. AB - We report a case of an HIV-infected adult with Chlamydia pneumoniae. Our patient presented with a clinical picture suggestive of Pneumocystis carinii pneumonia (PCP), but did not respond to empiric anti-PCP therapy. The diagnosis was eventually confirmed by bronchoscopy and serology. C. pneumoniae pneumonia should be considered in the differential of pathogens that cause interstitial infiltrates in HIV-infected persons. PMID- 1928226 TI - The role of the matrix metalloproteinase stromelysin in the progression of squamous cell carcinomas. AB - The expression of the metalloproteinase stromelysin correlates with the progression of chemically induced squamous cell carcinomas. We demonstrate that the expression of activated stromelysin in papilloma-derived cells enhances in vitro cell invasion. We also demonstrate that the Ha-ras oncogene induces the transcription of the stromelysin gene through an AP-1 dependent pathway. The hypothesis is that alterations in oncogenes and suppressor genes influence stromelysin expression and thus influence subsequent steps of tumor invasion and metastasis. PMID- 1928227 TI - Inflammatory phagocytes and connective tissue degrading metalloproteinases. PMID- 1928228 TI - So what's new with jun? AB - Cancer causing oncogenes are found in specific locations within the cell. Although a great deal is known about the function of the transforming genes that reside on the plasma membrane, less is known about the function of the oncogenes that reside in the nucleus. Studies performed over the last three years on the jun and fos oncogenes have taught us a great deal about how these cancer causing genes function in the nucleus. The products of the jun and fos protooncogenes appear to enhance the transcription of specific genes. The proteins form a heterodimer that binds to specific DNA sequences upstream from the start site of transcription and stimulate the production of messenger RNA. Recent data may explain how jun protein becomes transforming. Unlike normal jun protein, transforming jun protein lacks 30 amino acids. These 30 amino acids appear to bind a protein that inhibits the ability of the jun protoncogene to activate gene transcription. The change of cells from normal to transformed may be mediated partially by unrestrained activation of transcription. These findings suggest possible new targets for chemotherapy to inhibit cancer cell growth. PMID- 1928229 TI - Integrating substance abuse education in the medical student curriculum. AB - Physicians miss the diagnosis of substance abuse in significant numbers of patients, partly because of a lack of education about identifying and treating those patients. This article describes an attempt to integrate substance abuse into the curriculum of a traditionally organized medical school. Faculty selection, determination of the skills and knowledge needed, and methods for enriching the curriculum to include substance abuse are described. Problems encountered during the project, benefits of implementing the curriculum changes, and recommendations for other medical schools choosing to implement such a program also are provided. PMID- 1928230 TI - Primary pulmonary hypertension. AB - Primary pulmonary hypertension is a rare disease of unknown etiology, which mainly affects people in the third and fourth decades. Although the clinical cause is highly variable and spontaneous regression has been described, survival rates are usually poor, averaging only three years after diagnosis. Treatment with vasodilator agents, especially calcium channel blockers and prostaglandins, usually improves symptoms, but have not been shown to improve chances for survival. In a few selected patients who continue to deteriorate despite medical treatment, lung transplantation may be the only option for improving function and survival. PMID- 1928231 TI - Malignancy hypercalcemia: evaluation of parathyroid function and response to treatment. AB - In 53 patients with malignancy-associated hypercalcemia, we measured serum parathyroid hormone (PTH) with an immunoradiometric assay (IRMA) for intact PTH and a midregion-specific radioimmunoassay (RIA). Values were measured at baseline to detect clinically unrecognized hyperparathyroidism and after treatment with intravenous bisphosphonate to test for a parathyroid response. One patient probably had primary hyperparathyroidism, since his serum PTH values were not appropriately suppressed at baseline and increased markedly during treatment before normocalcemia was achieved. In each of the 51 other evaluable cases, the intact PTH value was suppressed below 25 pg/ml (normal range 10-55 pg/ml), confirming a nonparathyroid hypercalcemia. Midregion PTH values were less fully suppressed but supported the diagnosis in 44 out of 49 cases. The five patients with high midregion PTH values each had renal insufficiency but in four, the intact PTH values were also the highest we observed in these patients. This suggests either a poorly suppressible intact PTH secretion or prolongation of intact PTH half-life by the renal insufficiency. Overall, midregion and intact PTH values were highly correlated (p less than 0.001). Restoration of normocalcemia increased PTH in both assays into or within the normal range, and when posttreatment hypocalcemia occurred, PTH values became elevated in both assays. We conclude the following: (1) both assays are useful for detecting parathyroid hyperfunction but the intact PTH assay is the better diagnostic tool when renal insufficiency is present, (2) hypercalcemia seems to suppress intact PTH secretion more fully than secretion of PTH fragments, and (3) parathyroid glands chronically suppressed by hypercalcemia can increase PTH secretion within 1 or 2 days after the hypercalcemia is corrected. PMID- 1928232 TI - Metastatic tumor: the complementary role of the marrow aspirate and biopsy. AB - To determine whether bone marrow aspiration or biopsy is more sensitive in the detection of nonhematologic metastatic involvement of marrow, all 1569 consecutive paired biopsy and aspirate samples obtained between January 1975 and January 1, 1986 in an 800 bed municipal hospital were reviewed. At least eight aspirate slides and 10 biopsy cross sections were examined for each pair. In 39 samples, both biopsy and aspirate identified metastatic tumor. No biopsies contained tumor that was not also seen on the aspirate. However, five aspirate slides contained metastatic malignancies not identified on biopsy. The hematologist or oncologist viewing individual cells in a monolayer at 1000 x magnification has the advantage of identifying very small clusters of tumor cells. That accounted for three of the five positive aspirate samples in which the biopsies were negative. The other two positive aspirate slides each contained tumor on only one of eight slides. The results of our study indicate that when carefully reviewed, the aspirate is at least as sensitive as the marrow biopsy for identifying metastatic tumor. Our results indicate that marrow aspirates and biopsies are useful and complementary examinations for identifying metastatic malignancy. PMID- 1928233 TI - Case report: adult T-cell leukemia/lymphoma associated with recurrent strongyloides hyperinfection. AB - Adult T-cell leukemia/lymphoma (ATLL) was demonstrated postmortem in a 47-year old woman initially manifesting severe hypercalcemia and a vertebral compression fracture. Hyperinfection with Strongyloides stercoralis preceded the appearance of ATLL by several months and ultimately dominated the terminal course. Although HTLV-I and S. stercoralis commonly infect the same host, only three other cases of concomitant ATLL and hyperinfection have been reported in English. The apparent rarity of this association suggests that immunologic sequelae of ATLL do not predispose to dissemination and multiplication of Strongyloides. Observations pertinent to this conclusion are reviewed. PMID- 1928234 TI - Case report: metolazone-associated hypercalcemia and acute pancreatitis. AB - Metolazone-induced acute pancreatitis and hypercalcemia are described in a 58 year-old woman with severe congestive cardiac failure. Her symptoms and laboratory abnormalities rapidly resolved upon discontinuation of metolazone. Both clinical and laboratory findings make other etiologies for the patient's pancreatitis extremely unlikely. The pathophysiology of thiazide-related hypercalcemia and pancreatitis is reviewed. To our knowledge, neither hypercalcemia nor the combination of acute pancreatitis with hypercalcemia has been reported previously in association with metolazone therapy, and the association of pancreatitis and metolazone has been noted previously only once. PMID- 1928235 TI - Principles of intercultural medicine in an internal medicine program. AB - Internal medicine and medicine-pediatric residents (n = 76) completed a questionnaire that measured variables including sociodemographics, family dynamics, cross-cultural exposure, and exposure to intercultural medicine principles. Questions were answered regarding perceptions of their patients and level of comfort discussing specific cultural variables. Gender, training status, and geographic background did not influence responses, but the responses of European-Americans (71%) vs. ethnic minorities and foreign medical graduates (29%) were significantly different. European-Americans were more likely to be men, less likely to have an urban background (p = .02), and their self-described socioeconomic status was uppermiddle to upper class (p = .02). European-Americans vs. all others differed in their perceptions of patients' financial support (p = .001), and reasons for doctor-patient miscommunications (p = .05). The European Americans had significantly less exposure to friends and classmates (p = .002), and instructors (p = .0001) of ethnic origins different than their own prior to residency training. Our data support the inclusion of intercultural medicine principles in the general internal medicine curriculum. PMID- 1928236 TI - Renal cell carcinoma. AB - Renal cell carcinoma accounts for 3% of all adult cancers and has many unusual features in its presentation, diagnosis, and management. It develops in a significant number of patients with acquired renal cystic disease, a disorder found almost exclusively in chronic hemodialysis patients. Abnormalities of chromosome 3 are frequently found in sporadic and familial forms. Radical nephrectomy remains the only potentially curative therapy for this tumor. PMID- 1928237 TI - Cystoid macular edema, retinal detachment, and glaucoma after Nd:YAG laser posterior capsulotomy. AB - A series of 897 Nd:YAG laser posterior capsulotomies were reviewed for the complications of cystoid macular edema, retinal detachment, new onset of glaucoma, and worsened preexisting glaucoma. After Nd:YAG capsulotomy, 11 patients (1.23%; 95% confidence interval, 0.51% to 1.95%) developed cystoid macular edema and eight patients (0.89%; 95% confidence interval, 0.28% to 1.5%) developed a retinal detachment. The new onset of glaucoma was observed in seven patients (0.78%; 95% confidence interval, 0.20% to 1.36%). Five patients (0.56%; 95% confidence interval, 0.07% to 1.05%) with preexisting glaucoma had persistent worsening of their glaucoma. Most patients with a complication had no identifiable risk factors in common. The numbers of laser pulses and energy delivered were not risk factors. Retinal detachment and cystoid macular edema developed most often many months after capsulotomy and many months to years after the cataract surgery. Patients undergoing Nd:YAG laser capsulotomy therefore require ongoing medical observation to detect and treat these serious complications. PMID- 1928238 TI - Treatment of unilateral acute sixth-nerve palsy with botulinum toxin. AB - We studied 29 consecutive patients with acute unilateral sixth-nerve palsy, who received botulinum toxin injection to the antagonist medial rectus muscle. The average interval between onset of palsy and treatment was 40 days and the mean follow-up from the last injection was 14 months. Before treatment, esotropia in the primary position ranged from 12 to 45 prism diopters and limitation to abduction in the affected eye ranged from -2 (approximately 15 degrees lateral to midline) to -6 (15 degrees nasal to midline). After treatment, 22 of 29 patients (76%) had complete recovery of motility as determined by version testing. Of the seven patients with a residual abduction deficit, two had fusion in the primary position, three had fusion with prismatic correction, and two patients required subsequent surgery. Botulinum toxin injection seems to be an effective treatment option in cases of acute unilateral sixth-nerve palsy. PMID- 1928239 TI - The effects of lipid lowering on diabetic retinopathy. AB - The effect of lipid lowering on hard exudates was determined in six consecutive patients with insulin-dependent diabetes mellitus. Diet and hypolipidemic drug therapy including the use of pravastatin, a new inhibitor of 3-hydroxy-3 methylglutaryl coenzyme-A reductase, were used to treat patients for one year. The total cholesterol concentration decreased from a mean baseline value of 231 mg/dl to a treatment mean value of 165 mg/dl. The mean low-density lipoprotein cholesterol concentration decreased from 157 mg/dl to 93 mg/dl. Masked grading of fundus photographs indicated an improvement in hard exudates in all six patients and a decrease in microaneurysms in four patients. Visual acuity improved in one patient and did not change (one line or less change) in five patients. No remarkable side effects resulting from treatment were observed. Our pilot study suggests that aggressive therapy of diabetic patients with hyperlipidemia may have a beneficial effect on background retinopathy. PMID- 1928240 TI - Uveitis precipitated by nonpenetrating ocular trauma. AB - Although penetrating trauma is a well-recognized cause of uveitis, the role of nonpenetrating trauma in initiating uveitis is not defined. We analyzed the records of 496 patients seen at the uveitis clinic at our institution. Twenty four of these 496 patients (4.8%) suspected that the cause of their intraocular inflammation was related to previous nonpenetrating trauma. In contrast, only one of 251 patients (0.4%) attending the general ophthalmology clinic for routine care provided a history of recent trauma or attributed the present ocular complaint to trauma (P less than .02). Patients with posttraumatic uveitis were usually male (19 of 24, 79%), younger (31 +/- 16 years) than the average patient examined in the uveitis clinic, and more likely to have unilateral disease. In ten (42%) of the patients the trauma was work-related. Bilateral inflammation was seen in eight (one third) of the patients and 17 of 28 patients (71%) had a considerable degree of inflammation posterior to the lens. Many patients had an identifiable cause of uveitis such as ankylosing spondylitis, Reiter's syndrome, sarcoidosis, or acute retinal necrosis; but most patients had no known predisposition. The role of nonpenetrating trauma in initiating uveitis has implications for diagnosis and treatment. PMID- 1928242 TI - Management of the dislocated crystalline lens with a perfluorocarbon liquid. AB - Vitreoretinal surgery allows the effective removal of soft to moderately dense crystalline lens fragments, using the vitrectomy probe and the ultrasonic fragmentation probe. Hard lenses cannot be removed with these instruments. Previously described techniques for removal of hard lenses include trapping the lens anteriorly with needles, cryoextraction of the lens in an air-filled eye, and manipulation with sodium hyaluronate. These methods are difficult and dangerous in some cases. We used perfluorocarbon liquid to facilitate the safe removal of a surgically luxated hard crystalline lens. Injection of the perfluorocarbon liquid floated the lens off the retinal surface and into the anterior vitreous cavity. In this location, the lens was delivered by using standard extracapsular cataract extraction techniques. This technique allowed removal of the hard crystalline lens with minimal manipulation, and was helpful in the setting of poor media clarity. PMID- 1928241 TI - Retinal pigment epithelial tears associated with trauma. AB - Two previously healthy patients, a 66-year-old man with blunt trauma to the right eye, and a 28-year-old man with head trauma from a motorcycle accident, were observed to have parafoveal retinal pigment epithelial tears after injury. In both patients, fluorescein angiography demonstrated mottled window defects in the areas of the tears, and blocked fluorescence in the areas of the rolled-up pigment epithelium. Neither eye had evidence of pigment epithelial detachments. We hypothesize that this unusual phenomenon is caused by an acute tractional force oriented tangentially to the macular plane, the result of a rapid spherically expansile deformation of the globe during trauma. PMID- 1928243 TI - Familial congenital grouped pigmentation of the retina. AB - Congenital grouped pigmentation of the retina is an uncommon disorder characterized by a grouping together of round to oval spots of pigment in one or more quadrants of the retina, except for the macula. Detection is usually coincidental during routine ocular examination. We examined a mother and daughter with bilateral grouped pigmentation of the retina. Visual acuity, visual fields, and results of electrophysiologic examination were normal. Autosomal dominant inheritance with variable expression was likely. PMID- 1928244 TI - Subepithelial infiltrates in Acanthamoeba keratitis. AB - Six patients had Acanthamoeba keratitis that manifested an unusual type of subepithelial corneal infiltrate late in the course of the disease. These infiltrates occurred in the anterior corneal stroma, often in a location removed from the site of infection. In four of these patients the infiltrates occurred with no other clinical signs of inflammation. Two patients had mild foreign-body sensation that resolved despite the persistence of the subepithelial infiltrates. The infiltrates resolved with topical corticosteroid therapy in three patients; however, in two of these three patients the infiltrates recurred when corticosteroid therapy was tapered or discontinued. The subepithelial infiltrates appeared and behaved similarly to those associated with viral and chlamydial corneal infections. An immunologic mechanism may be responsible for these unusual delayed-in-onset infiltrates. PMID- 1928245 TI - The effects of denatured sodium hyaluronate on the corneal endothelium in cats. AB - In an in vivo cat model, wide-field specular microscopy and scanning electron microscopy were used to observe whether heat-denatured sodium hyaluronate causes cell damage to the corneal endothelium. The endothelial cell toxicities of various drugs, including 0.01% benzalkonium chloride, 0.2% chlorhexidine digluconate, and 0.5% lidocaine, mixed with intact or untreated sodium hyaluronate were also investigated. Neither heat-denatured nor intact or untreated sodium hyaluronate alone had any adverse effect on the corneal endothelium in cats, whereas 0.01% benzalkonium chloride and 0.2% chlorhexidine digluconate, mixed with sodium hyaluronate, caused substantial endothelial morphologic changes, which resulted in corneal edema. By comparison, 0.5% lidocaine with sodium hyaluronate was found to have minimal effect on the corneal endothelium in cats. These findings indicate that some chemical contaminant with sodium hyaluronate, not heat-denatured sodium hyaluronate, induces an immediate onset of pseudophakic bullous keratopathy. PMID- 1928246 TI - Evaluation of dacryocystorhinostomy failure with computed tomography and computed tomographic dacryocystography. AB - Five patients with dacryocystorhinostomy failures were examined with computed tomography or computed tomographic dacryocystography. In computed tomographic dacryocystography, radiopaque dye was instilled into the lacrimal sac before computed tomography to show its shape, location, and relation to surrounding structures. Problems with the bony ostium were detected in all five patients. Recurrent nasal polyposis, a retained metallic clip, and an unresected ethmoid air cell were also identified. Computed tomography and computed tomographic dacryocystography provided important information that facilitated reoperation after dacryocystorhinostomy failure. PMID- 1928247 TI - Congenital entropion with intact lower eyelid retractor insertion. AB - Congenital lower eyelid entropion is generally considered to result from improper development of the retractor aponeurosis insertion to the inferior portion of the tarsal plate. We treated three patients with this uncommon disorder. At operation, aponeurotic defects were anticipated and specifically sought, but in each case the lower eyelid retractors were inserted normally. In two patients, entropion was relieved by surgical disinsertion and then advancement of the retractors. In the third patient, who also had multiple concomitant facial and systemic developmental anomalies, improvement in the lower eyelid malpositions required a combination of procedures. The intraoperative findings in our patients demonstrate that disinsertion of the lower eyelid retractors is not a universal etiologic mechanism in congenital entropion. PMID- 1928248 TI - Retinoblastoma manifesting as orbital cellulitis. AB - Five children with previously undiagnosed retinoblastoma had signs of unilateral orbital cellulitis and were treated with systemic antibiotics, corticosteroids, or both. When retinoblastoma was finally diagnosed clinically, radiologists believed in every case that, on the basis of the soft-tissue swelling seen with computed tomography, there was orbital extension of the tumor. However, intraoperative and histopathologic observations disclosed no demonstrable orbital tumor involvement. The affected eyes all had neovascular glaucoma, and all harbored highly necrotic tumors that were contained within the eye. We concluded that orbital inflammation can occur with retinoblastoma confined to the eye and that signs of orbital cellulitis do not necessarily imply orbital extension of the tumor. PMID- 1928249 TI - Marked intraocular pressure response to instillation of corticosteroids in children. AB - We examined intraocular pressures of patients with strabismus whose eyes were instilled with corticosteroid eyedrops after a strabismus operation. Group A consisted of 11 children under 10 years of age whose eyes were instilled with 0.1% dexamethasone; Group B consisted of nine patients 10 years old or older whose eyes were instilled with 0.1% dexamethasone; and Group C consisted of 13 children under 10 years of age whose eyes were instilled with 0.1% fluorometholone. In Group A, four patients had intraocular pressures greater than 30 mm Hg, five had intraocular pressures from 21 to 30 mm Hg, and two had intraocular pressures under 21 mm Hg one or two weeks postoperatively. The intraocular pressure decreased to less than 21 mm Hg one week after discontinuation of dexamethasone treatment in all nine patients. No patients in Groups B or C had intraocular pressures greater than 20 mm Hg. Our results suggest that marked ocular hypertensive response to 0.1% dexamethasone treatment occurs frequently in children under 10 years of age. PMID- 1928250 TI - The American Board of Ophthalmology turns 75. PMID- 1928251 TI - Rhegmatogenous retinal detachment after initiation of ocusert therapy. PMID- 1928252 TI - Mixing fortified antibiotic eyedrops. PMID- 1928253 TI - Tuberculous choroiditis diagnosed by chorioretinal endobiopsy. PMID- 1928254 TI - Granulomatous uveitis and quinidine hypersensitivity. PMID- 1928255 TI - Prevalence of Lyme disease among patients with uveitis. PMID- 1928256 TI - Asymmetric pigmentary dispersion syndrome mimicking Horner's syndrome. PMID- 1928257 TI - Acute conjunctivokeratouveitis caused by latex from the pencil tree. PMID- 1928258 TI - Concurrent chlamydial and Acanthamoeba keratoconjunctivitis. PMID- 1928260 TI - Canalicular obliteration from toxic epidermal necrolysis. PMID- 1928259 TI - Bilateral herpes simplex keratitis in a patient with graft-vs-host disease. PMID- 1928261 TI - Metastatic carcinoid tumor diagnosis from a caruncular mass. PMID- 1928262 TI - Immunohistochemistry findings in primary intraocular lymphoma. PMID- 1928263 TI - The elastic properties of the lens capsule in capsulorhexis. PMID- 1928264 TI - Ultrastructural study of Norrie's disease. PMID- 1928265 TI - Unilateral frosted branch angiitis. PMID- 1928266 TI - The comparative in vitro activity of ofloxacin and selected ophthalmic antimicrobial agents against ocular bacterial isolates--correction. PMID- 1928267 TI - Current therapy for bacterial keratitis and bacterial conjunctivitis. AB - Therapy of bacterial keratitis and conjunctivitis requires that antibiotics be administered to eliminate viable bacteria. Only a limited number of ophthalmic antibiotics are commercially available. Although generally adequate for the treatment of bacterial conjunctivitis, the commercial preparations are believed to contain too low a concentration of antibiotic for the treatment of bacterial keratitis. Using products designed for parenteral administration, the ophthalmologist or the pharmacist formulates so-called fortified preparations containing much higher antibiotic concentrations. Because of their limited spectrum of action, two fortified preparations generally are administered concurrently. Topical application is the most effective route of antibiotic administration for treatment of bacterial keratitis. Antibiotics may also be injected periocularly, a method with risk, or intravenously, a method of uncertain efficacy. PMID- 1928269 TI - A review of bacterial keratitis and bacterial conjunctivitis. AB - Bacterial keratitis is an opportunistic infection of the avascular corneal stroma, initiated by a breakdown of the epithelial barrier. Corneal abrasion with infected material, extended-wear contact lenses, eyelid disease, and disorders of the ocular surface are predominant contributing factors. Acute bacterial conjunctivitis occurs when sufficient bacteria are introduced into the fornices to overwhelm normal bacteriostatic and flushing mechanisms. Chronic conjunctivitis is associated with a constant adnexal source of bacteria and resolves when the source is successfully treated. Rapid diagnosis and treatment of bacterial keratitis are essential to limit stromal scarring and minimize visual loss. PMID- 1928268 TI - Microbiologic aspects of fluoroquinolones. AB - Fluoroquinolones are both old and new antimicrobial agents. The prototype agent of the class, nalidixic acid, was synthesized in 1962, whereas the new fluoroquinolones began to be used in the latter 1980s. During the past six years, orally administered fluoroquinolones have been used extensively in Japan and Europe to treat both community- and hospital-acquired infections. Most recently, one of the fluoroquinolones, ciprofloxacin, has also become available for parenteral and topical ophthalmic use. This article reviews the chemistry, antimicrobial activity, pharmacology, and clinical use of the fluoroquinolones. PMID- 1928270 TI - Insights from experimental data on ciprofloxacin in the treatment of bacterial keratitis and ocular infections. AB - Ciprofloxacin is a potent fluoroquinolone antibiotic with in vitro activity against many significant gram-positive and gram-negative ocular pathogens. A review of the experimental studies of this antibiotic shows bactericidal activity, a broad antimicrobial spectrum, and a low incidence of resistance. The growing body of experimental data supports the effectiveness of ciprofloxacin in the treatment of experimental keratitis and suggest that it be evaluated further in ocular infections. PMID- 1928271 TI - Antibacterial effectiveness of ciprofloxacin 0.3% ophthalmic solution in the treatment of bacterial conjunctivitis. AB - Two hundred eighty-eight cases of culture-proven bacterial conjunctivities were evaluated as part of two multicentered, randomized, prospective clinical studies comparing the antibacterial efficacy of topically administered ciprofloxacin 0.3% either with a placebo or with tobramycin 0.3%. In the first study, ciprofloxacin was significantly (P less than .001) more effective than the placebo. It eradicated or reduced the various bacterial pathogens in 93.6% of patients, compared to 59.5% for the placebo. In the second study, ciprofloxacin (94.5%) and tobramycin (91.9%) were equally effective. Topically applied ciprofloxacin eradicated or reduced all isolated bacterial species, attesting to its broad antibacterial spectrum and its potential usefulness in treating external ocular infections. PMID- 1928272 TI - Clinical evaluation of ciprofloxacin 0.3% ophthalmic solution for treatment of bacterial keratitis. AB - A multicenter, prospective clinical study of 148 culture-proven cases of bacterial keratitis, treated with ciprofloxacin 0.3% ophthalmic solution, compared its clinical and antibacterial efficacy with the standard therapy regimen of each investigator. Most often, this consisted of topically administered fortified cefazolin (33 mg/ml) and fortified gentamicin or tobramycin (14 mg/ml). Two control groups were studied: (1) patients treated while the ciprofloxacin study was ongoing (not enrolled group); and (2) patients treated during the year before initiation of the ciprofloxacin study (historical group). Treatment with ciprofloxacin yielded a 91.9% success rate. Standard therapy yielded an 88.2% success rate among not enrolled control patients and an 88.3% success rate among the historical control patients. No serious side effects accompanied ciprofloxacin administration. In vitro susceptibility testing showed ciprofloxacin to be highly effective against bacterial corneal pathogens. These findings suggest that ciprofloxacin 0.3% is safe and effective as a single agent for the treatment of bacterial keratitis. PMID- 1928273 TI - Occupational therapy's new mandate: providing services to the elderly. PMID- 1928274 TI - From Ellis Island to assisted living: meeting the needs of older adults from diverse cultures. AB - Among the rapidly increasing population of older adults, the minority elderly have also been increasing in numbers and are projected to grow at a more rapid rate than the white population well into the next century (American Association of Retired Persons, 1989). This factor, together with the existence of substantial ethnic diversity among both white and minority elders, mandates that our profession examine how we address the associated needs of all older adults who receive occupational therapy services in order to promote optimal performance and quality of life. Rationales for providers to increase personal awareness of these factors as basic contextual determinants in providing services are offered. The inclusion of cultural and ethnic considerations in all interventions with older adults as critical components in the provision of quality service is given, together with suggestions for methods of implementation. PMID- 1928275 TI - Addressing the needs of the cognitively impaired elderly from a family policy perspective. AB - Management of the cognitively impaired elderly person in the community is presumed to be cost-efficient and the American way. Although this is what should be done, most would agree that paying for the services that make it possible to do so is not currently within the means of the median income of the family ($25,986) or of the female head of household ($15,350) in this country. This paper reviews the changes in the family, current family policies, and practices of our businesses and government and proposes the services that could be used to support both the impaired person and the family in the management of this evolving societal issue. Strategies for development of payment mechanisms for the proposed services are presented. PMID- 1928276 TI - Long-term care of the aged: ethical dilemmas and solutions. AB - This article identifies the need to rethink beliefs and assumptions about the bioethics of long-term care of elderly people. An unconventional way of conceptualizing autonomy is explored that may help occupational therapists support and maintain the independence of older frail and dependent persons. In addition, the partnership model of bioethics is introduced-that is, an ethical framework that makes partners of family members in health care decisions affecting the older adult. PMID- 1928277 TI - Occupational therapy in the Department of Veterans Affairs: focus on health care of the elderly veteran. AB - The Department of Veteran Affairs (VA) operates the largest integrated health care system in the world (VA, 1989), with designated departments and programs designed to meet the long-term care needs of the aging veteran. Occupational therapy is an important intervention to maximize the quality of life of older persons. Because of the increasing number of aging veterans and the national shortage of occupational therapists, the VA has been devising programs to recruit and retain occupational therapists in VA medical centers. The combination of long term care programs and the VA's commitment to ongoing research, education, and occupational therapy services points to a promising outlook for care of our aging veterans. PMID- 1928278 TI - Private practice occupational therapy in the skilled nursing facility: creative alliance or mutual exploitation? AB - Occupational therapy private practice appears to play a major role in the provision of rehabilitation services in skilled nursing facilities. A critical look at the meaning of private practice, however, indicates that many of today's private practitioners lack characteristics traditionally associated with that term. Group private practices are well suited to retain the essential qualities of private practice while competing effectively in a corporate environment. They accomplish this difficult task by applying therapeutic principles of growth and change to the complex relationship between the group practice and the skilled nursing facility. Application of these principles allows the occupational therapy group private practice to behave consistently with its professional identity while addressing the competitive demands of the marketplace. PMID- 1928279 TI - Long-term care and federal policy. AB - A major deficiency of national health care policy is the lack of a structured and comprehensive system of long-term care. A review of existing federal programs reveals that substantial resources are being expended to care for the elderly. Program structures and requirements, however, are frequently skewed toward institutional care to the exclusion of more appropriate home- and community-based services. A recent federal study highlighted the dimensions of the long-term-care problem and proposed a compelling remedy, but a consensus continues to elude policymakers, and the prospects for fundamental reform are uncertain. PMID- 1928280 TI - Educating entry-level occupational therapy students in gerontology. AB - The need for gerontic occupational therapists is increasing as the number of elders increases. The practice of including gerontologic content in occupational therapy entry-level curricula is relatively new. This article provides a rationale for including gerontologic content in entry-level occupational therapy curricula and presents the results of a brief survey conducted in November 1990 of all accredited and developing entry-level professional occupational therapy programs in the United States. Seventy-one percent of the entry-level programs responded. All of the responding programs included some gerontologic content in their curricula, and 82% of the responding programs indicated that the amount of gerontologic content in the required curriculum had increased in the past 5 years. Other gerontologic elements examined were courses offered and topics included in entry-level curricula, textbooks used, and gerontic fieldwork requirements. PMID- 1928281 TI - Dressing training for an elderly woman with cognitive and perceptual impairments. PMID- 1928283 TI - The challenge of research in occupational therapy. PMID- 1928282 TI - Strategies for increasing referrals for occupational therapy in home health care. AB - The paucity of home health care referrals for occupational therapy led us to develop an educational approach to increase both the referral sources and the number of referrals to occupational therapy. With a consistent effort to exercise clearly identified strategies, the occupational therapy referrals at the Visiting Nurse Association of Porter County, Indiana, increased threefold from the number of referrals at the same time last year. The greater staff awareness of the need for occupational therapy in home health care requires occupational therapists to continually prevent old nonreferring habits from reemerging and to orient and educate new staff members as they enter the home health care field. PMID- 1928284 TI - Occupational therapy in the 21st century: an outsider's view. PMID- 1928285 TI - Ethics across the occupational therapy curriculum. AB - The authors describe the development of specific teaching modules, methods, and techniques with which to raise student consciousness and generate awareness of ethical issues in occupational therapy practice as well as to develop the ethical decision-making process through the use of three ethical decision-making and thinking models. This focus on ethics has been integrated into the entire 2-year occupational therapy curriculum at a liberal arts college as part of the college's larger institutional mission and objectives. The results obtained from informal faculty and student contacts and students' feedback after completion of clinical fieldwork demonstrate increased student sensitivity and ability to identify and discern ethical issues as well as increased awareness of the many professional complexities involved in the determination of decisive proactive responses. PMID- 1928286 TI - Pragmatic learning and media courses at New York University. AB - The responses of students who were exposed to pragmatic and conventional learning models with regard to activities were analyzed and compared for content. Seventeen categories representing the students' thoughts and feelings about crafts emerged from the content analysis. These categories were divided into three content areas: pragmatic concepts, nonpragmatic concepts, and feelings. The 17 concepts were subjected to statistical analysis (i.e., group t tests). As anticipated, exposure to the pragmatic learning model resulted in significant positive changes in pragmatic concepts and feelings and, to a lesser degree, in nonpragmatic concepts. Additionally, exposure to the pragmatic learning model resulted in fewer negative remarks about crafts and their use in therapy. These findings were supported by a case study and may aid educators in designing media education courses. PMID- 1928287 TI - Volumetric comparison of seated and standing test postures. AB - Published protocols for the volumetric assessment of upper-extremity edema differ regarding patients' posture. The present study was designed to determine the effect of posture on test-retest reliability and mean volume. Thirty women were tested in both seated and standing postures. For the dominant hand, test-retest reliabilities for the seated posture were identical to those for the standing posture. Test-retest reliability was slightly stronger for the nondominant hand in sitting than for the same hand in standing. Both postures afforded clinically acceptable test-retest reliabilities. The mean volumes in sitting were significantly lower than those in standing (p less than .0001), thus suggesting that volumetric measures should be considered discontinuous if the patient's test posture is altered. Mean volumes of the dominant hand averaged 9.3 ml more than those of the nondominant hand. It is suggested that this discrepancy be considered in the establishment of goals for edema control and in the determination of the need for continued edema treatment. PMID- 1928288 TI - Motor function and activities of daily living assessments: a study of three tests for persons with hemiplegia. AB - The relationship between upper extremity motor function and independence in basic activities of daily living in subjects with hemiplegia was explored. The Barthel Index (Mahoney & Barthel, 1965) and the Fugl-Meyer Test (Fugl-Meyer, Jaasko, Leyman, Olsson, & Steglind, 1975) were selected as the standard instruments for the evaluation of activities of daily living and upper extremity motor function, respectively, because their validity and reliability have been demonstrated many times. The Functional Test for the Hemiplegic/Paretic Upper Extremity (Wilson, Baker, & Craddock, 1984a, 1984b) was also used for the evaluation of upper extremity motor function. The results obtained in 18 subjects with hemiplegia indicate that the scores on the Barthel Index are poorly correlated with both the Fugl-Meyer Test and the Functional Test for the Hemiplegic/Paretic Upper Extremity scores. It is suggested that variables other than motor function, such as the learning of compensatory techniques and perceptual-cognitive status, are responsible for this discrepancy because they can influence activities of daily living performance in persons with hemiplegia. The high correlation between the scores on the Fugl-Meyer Test and the Functional Test for the Hemiplegic/Paretic Upper Extremity indicates that either test may be used for the assessment of upper extremity motor function. PMID- 1928289 TI - Self-esteem of persons with cerebral palsy: from adolescence to adulthood. AB - A longitudinal study of self-esteem in 22 adolescents with cerebral palsy is reported. The subjects were matched with nondisabled adolescents by age, sex, IQ, and school. Seven years later, 39 of the 44 subjects (mean age = 22.8 years) completed the Tennessee Self-Concept Scale (Roid & Fitts, 1988), the Social Support Inventory (McCubbin, Patterson, Rossman, & Cooke, 1982), and a demographic questionnaire with some open-ended questions. As adolescents, the girls with cerebral palsy scored significantly lower than the other groups on physical, social, and personal self-esteem; however, as adults, these subjects were no longer significantly different from the other groups. Male subjects with cerebral palsy had self-esteem scores similar to those of the nondisabled groups in both adolescence and adulthood. Demographic information is summarized. The factors that the subjects identified as leading to changes in self-esteem were relationships and experiences. The low self-esteem scores indicate that psychosocial occupational therapy intervention with adolescent girls with cerebral palsy and with some adults with cerebral palsy would be appropriate. PMID- 1928290 TI - A model for database design. AB - Computerized databases can facilitate several types of occupational therapy research. The value and usefulness of any database, however, is dependent on how well it has been designed. In this paper, a systematic, sequential-process model for the development of a computerized database is introduced. Each component of the model is illustrated by examples of its application to the actual design of a database for a community agency that provides occupational therapy services. The model focuses on issues related to the development of the contents of a database rather than on computer hardware and software. The issues addressed by the model include decisions about the purpose of the database, selection of the variables, and identification of the most appropriate measures with which to operationalize these variables. Content-related development issues have been given little attention in the literature, yet their neglect typically results in important limitations on the usefulness of a database. Therefore, this paper provides a set of guidelines for occupational therapists planning to establish a database for facilitating research. PMID- 1928291 TI - Occupational therapy in geriatric mental health. AB - Elderly persons with psychiatric disorders often experience a variety of functional deficits that affect their independence, safety, and activity level. The occupational therapist's role in addressing these needs is discussed, as are the possibilities for improvement of the elderly person's autonomy, safety, and integrity. Barriers to optimal service provision in the health care and social service systems as well as in occupational therapy are addressed. PMID- 1928292 TI - A belly gutter splint for proximal interphalangeal joint flexion contracture. AB - Various splints are available for the correction of proximal interphalangeal (PIP) joint flexion contracture in patients with hand injuries. This article discusses the mechanics of several splints. The belly gutter splint, an alternative design that can be used for this contracture, is introduced. PMID- 1928293 TI - Occupational therapy intervention for an adult with depression and suicidal tendencies. AB - A hospitalized patient with depression and suicidal tendencies was referred for occupational therapy. The patient's evaluations while hospitalized indicated a lack of social skills and unrealistic expectations concerning abilities and aspirations. A work evaluation showed high scores in artistic and people-related occupations. Treatment focused on improvement of self-image, social interaction abilities, and stress management skills that would assist the patient in obtaining and keeping a job. Increased knowledge of vocational options and selection of an appropriate training program led to a job placement that the patient has enjoyed and maintained for the past 2 years. PMID- 1928294 TI - Poor handwriting: who is referred? PMID- 1928296 TI - Detection and cellular localization of human C4 gene expression in the renal tubular epithelial cells and other extrahepatic epithelial sources. AB - Although the liver is the major source of most complement proteins, recent reports have characterized extrahepatic expression of the genes for some of these components in a variety of tissues. In most cases, however, the specific cell type responsible for the extrahepatic complement expression has not been determined in situ. The authors studied expression of the fourth component of complement (C4) in a variety of human tissues by Northern analysis and by in situ hybridization. The C4 gene was found to be expressed at high levels in liver and both normal and diseased kidneys. In addition, evidence of C4 gene expression was found in the small intestine and brain. By in situ hybridization, the renal C4 gene expression was exclusively localized to tubular epithelial cells. C4 expression was also identified in hepatocytes, thyroid follicular epithelial cells, and ductal epithelial cells of the submandibular salivary gland. Although it is unlikely that local expression of the C4 gene contributes to glomerulonephritis, these results indicate that some components of complement may have a physiologic role in epithelial cell function. PMID- 1928295 TI - Expression of tumor necrosis factor in human acute cardiac rejection. An immunohistochemical and immunoblotting study. AB - The authors performed an immunohistochemical study on expression of tumor necrosis factor alpha (TNF alpha) in endomyocardial biopsies from human cardiac allografts. TNF alpha immunoreactivity was found in 45% biopsies with mild acute rejection, in 83% biopsies with focal moderate rejection, in 80% biopsies with diffuse moderate rejection. Biopsies with absent rejection did not show immunoreactive cells. In mild rejection, positive cells were few and scanty monocytes and macrophages (MAC-387 and LN5 positive cells) and T lymphocytes (UCHL-1/CD45 RO positive cells) (up to 20% of all infiltrating cells). Expression of major histocompatibility complex (MHC) class II antigens on infiltrating and endothelial cells occurred earlier and independent of TNF alpha reactivity. Number of immunoreactive cells increased in moderate rejection (up to 50%). Immunoreactivity was also present in nonpigmented macrophages in part of the biopsies with resolving rejection (45%). The authors conclude that TNF alpha is expressed in acute cardiac rejection by immunologically activated inflammatory cells. Immunoreactive cells increase in number with increasing severity of the reaction. PMID- 1928298 TI - Aberrant accumulation of phospholipase C-delta in Alzheimer brains. AB - Since phosphoinositide-specific phospholipase C (PLC) is one of the key molecules in signal transduction, the authors assessed its involvement in Alzheimer's disease (AD). Immunostaining of a specific antibody against the PLC isozyme, PLC delta, demonstrated that this enzyme was abnormally accumulated in neurofibrillary tangles (NFT), the neurites surrounding senile plaque (SP) cores, and neuropil threads in AD brains. Western blot analysis confirmed that PLC-delta was concentrated in the paired helical filament (PHF)-rich fraction of AD brains. Antibodies to other PLC isozymes did not produce positive immunostaining of these pathologic structures. Moreover, diffuse and amorphous deposits of PLC-delta were found to precede the accumulation of fibrillary deposits. These results suggest that PLC-delta accumulation is a crucial event that ultimately may contribute to the formation of PHF. PMID- 1928297 TI - Perforin mRNA expression in the inflamed tissues of NZB/W F1 lupus mice decreases with methylprednisolone treatment. AB - Perforin is one of the important cytolytic factors in cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. In this study, the authors examined perforin mRNA levels in the kidney, spleen, liver, lung, heart, and brain of NZB/W F1 lupus mice and NZW mice. Perforin mRNA levels in the kidney, spleen, liver, and lung of NZB/W F1 mice increased significantly with age, whereas those in the heart and brain of NZB/W F1 mice showed little change between 2 and 10 months of age. In all tissues examined in NZW, control mice perforin mRNA levels showed little change during the experimental period. In addition, the authors examined the effect of methylprednisolone (MPSL) on perforin gene expression in the tissues of NZB/W F1 mice. MPSL ameliorated the increase in perforin mRNA levels in the kidney, spleen, liver, and lung of NZB/W F1 mice. These findings suggest that perforin may contribute to tissue injuries in autoimmune lupus mice and that MPSL may be effective in lupus partly by decreasing perforin expression. PMID- 1928299 TI - Endothelial cells transformed by SV40 T antigen cause Kaposi's sarcomalike tumors in nude mice. AB - Injection into nude mice of a well-differentiated SV40 T-antigen-transformed murine endothelial cell (EC) line results in widespread invasive tumors confined to connective tissues. The tumors, which do not metastasize, consist of both host derived cells and transformed EC, displaying histologic features typical of Kaposi's sarcoma (KS). Although the EC is believed to be the cell of origin in KS, this has not been proven and is the subject of debate. The unusual tumorigenicity of this transformed cell suggests that EC-specific gene products induced by SV40 T antigen may contribute to tumorigenesis by autocrine growth stimulation and recruitment of host cells. KS-like tumors may be the result of EC alteration by any virus that induces relevant EC-derived cytokines. PMID- 1928300 TI - Renal disease in carrier female dogs with X-linked hereditary nephritis. Implications for female patients with this disease. AB - Male dogs with X-linked hereditary nephritis (HN) serve as a model for studying male patients with this disease. In the present study, carrier female dogs were found to resemble female patients in showing a broad range of renal dysfunction. Of 37 carrier female dogs studied, all were healthy up to 5 years of age; however, all had proteinuria develop at 2 to 3 months, and focal segmental glomerulosclerosis (FSGS) was detected after 7 months. After 5 years, 4 of 13 dogs remained healthy and showed mild FSGS on renal biopsy; 4 had mild renal dysfunction develop and their kidneys showed extensive FSGS; 5 died prematurely of renal failure with end-stage kidneys. By immunofluorescence, using antibody to the NC1 domain of collagen type IV, segmental staining of glomerular basement membranes (GBM) was seen in all dogs before 3 to 4 years, and lesions of FSGS were negative. Thereafter, a transition to global staining of GBM was noted and lesions of FSGS became positive. Lens capsule and basement membranes in lung and choroid plexus showed discontinuous staining in two young carrier female dogs and continuous staining in one older carrier female dog. By electron microscopy, multilaminar splitting of some GBM was seen up to 4 years, and thereafter, splitting took on a compressed appearance, with the layers becoming apposed though still detectable. The authors conclude that: 1) carrier female dogs with X linked HN are mosaics for an abnormality in the NC1 domain of GBM and other basement membranes; 2) FSGS develops in all carrier female dogs in glomerular capillary loops that possess an abnormal NC1 domain, and progresses to a variable extent in different dogs; and 3) the abnormality of NC1 in GBM of carrier female dogs appears to diminish with age, but this does not prevent progression of renal disease. Similar conclusions may apply to females with X-linked HN. PMID- 1928301 TI - Immunohistochemical localization of integrins in the normal, hyperplastic, and neoplastic breast. Correlations with their functions as receptors and cell adhesion molecules. AB - Integrins comprise a family of transmembrane glycoproteins that modulate cell matrix and cell-cell relationships by acting as receptors to extracellular protein ligands, and also as direct adhesion molecules. The authors studied by immunohistochemistry the distribution of the alpha 1-6,v and the beta 1,3,4 subunits of integrins in samples of normal breast, the spectrum of fibrocystic disease (FCD), and representative benign and malignant neoplasms. Monoclonal antibodies (Mabs) specific for each subunit were applied to cryosections by the avidin-biotin-complex method; selected samples were studied by double immunofluorescence microscopy with the Mabs and a polyclonal antiserum to myosin. The authors found that the alpha 1-3,6,v and the beta 1, integrin subunits were detectable in the normal breast parenchyma; myoepithelial cells were consistently more prominently stained than the basolateral aspect of the luminal cells. This immunoprofile was retained, and in cases enhanced through the spectrum of FCD, in benign tumors and in ductal and lobular carcinomas in situ. In most infiltrating ductal carcinomas, integrin staining tended to decrease except for some cases that reacted strongly for the alpha v subunit. Several mucinous carcinomas reacted strongly for alpha 2,3,6,v and beta 4 subunits, and even more so for the alpha 5 subunit that was not found in the normal breast. Subsets of infiltrating lobular carcinomas stained convincingly for alpha 1,3,6,v and beta 1 subunits in delicate but abundant kinetopodia. Our findings indicate that in hyperplasias and in benign tumors integrin expression patterns parallel those of the normal breast, whereas in carcinomas, variations include decrease, enhancement, and emergence of certain subunits that are not in the normal repertory. Alterations of integrin expression parallel phenotypic changes in breast carcinoma cells; they also reflect their disrupted interaction with the similarly disrupted extracellular matrix. Enhancement of certain integrins in some carcinomas may reflect the selection of subpopulations with increased binding capacity which in turn may impact on their invasive and metastatic properties. PMID- 1928302 TI - Detection, localization, and quantitation of HIV-associated antigens in intestinal biopsies from patients with HIV. AB - This study determined the prevalence, cellular localization, and content of human immunodeficiency virus (HIV)-associated antigens in intestinal mucosa from HIV infected subjects. Studies were performed in 168 subjects with gastrointestinal, nutritional, or proctologic complaints, and HIV-seronegative controls. The polymerase chain-reaction technique, which detects viral DNA, was used in 20 subjects and was positive in 70%. In situ hybridization studies, using RNA probes, were employed in 48 cases and were positive in 31%. Immunohistologic studies using monoclonal antibodies to HIV p24 antigen were employed in 73 cases and were positive in 67%. Quantitative ELISA assays for tissue p24 content were performed in 168 cases and was positive in 68%. Evidence of HIV was found throughout the intestine and in different disease stages. The quantitative ELISA studies correlated significantly with in situ hybridization, implying a possible association between the presence of viral RNA and protein expression. The authors conclude that HIV is present in intestinal mucosa from most, if not all HIV infected subjects. The relationship to intestinal disease currently is unclear. PMID- 1928303 TI - Mechanisms of clearance of immune complexes from peritubular capillaries in the rat. AB - These experiments evaluated extraglomerular sites of renal immune complex (IC) deposition and specific features of host capability to remove these IC. Ex vivo perfusion of rat kidneys with the endothelium binding lectin concanavalin A (con A) followed by rabbit anti con A IgG results in a subendothelial IC nephritis in glomerular capillaries (GC) and diffuse IC formation with complement (C3) deposition in peritubular capillaries (PC). Histologic, immunofluorescence, and ultrastructural studies were performed at 10 minutes and 1, 4, and 24 hours after perfusion. At 10 minutes, strong linear binding of con A, rabbit IgG, and rat C3 to the endothelium was detected by immunofluorescence in both GC and PC. In GC this was followed by endothelial cell swelling and denudation (1 hour) with platelet and neutrophil infiltration and formation of subendothelial IC deposits which persisted at 4 and 24 hours. In contrast, some PC endothelial swelling was also present at 10 minutes and 1 hour, but ICs (IgG, con A, C3) were capped and shed into capillary lumina at 1 to 2 hours with complete clearance of IC by 4 hours. Selective neutrophil depletion, by antisera and irradiation, and complement depletion with cobra venom factor, delayed clearance of PC IC by several hours but complete clearance of IC with restored structural integrity of PC was still achieved by 24 hours. Platelet depletion had no effect on PC IC clearance. These studies demonstrate a model for study of PC IC. Such a model may aid our understanding of lupus nephritis in which extensive GC IC deposits associated with severe inflammatory injury may coexist with PC deposits. Efficient clearance of IC in PC compared with GC may be due to differences in hemodynamic forces, amounts of IC formed in each of these sites, differences in binding of IC to subendothelial basement membrane, or phenotypic specialization of the endothelium lining these two different capillary beds. PMID- 1928305 TI - Immunohistochemical localization of extracellular matrix components in human diabetic glomerular lesions. AB - The immunohistochemical localization of the extracellular matrix was examined in 31 cases with different degrees of human diabetic nephropathy using antisera to human collagen types I, III, IV, V, fibronectin, laminin, and basement-membrane associated heparan sulfate proteoglycan (HSPG). In normal glomeruli, HSPG was predominantly localized in the glomerular basement membrane and in the mesangium, and to minor extent in the basement membranes of tubules and Bowman's capsule. Collagen IV and laminin were distributed in glomerular basement membrane and mesangium in minor amounts. Interstitial collagens usually do not occur within glomeruli except for collagen V which has a light microscopic glomerular distribution similar to collagen IV. In diabetic diffuse glomerulosclerosis, the enlarged mesangial matrix showed an increased staining reaction for collagen IV, V, laminin, and fibronectin whereas the staining pattern of HSPG was markedly reduced. Early, small nodular lesions in diabetic glomeruli were similarly positive for most of the basement membrane components, whereas HSPG remained absent. With an increase in the diameter of the noduli, however, the staining reaction for all basement membrane components diminished, whereas interstitial collagens V and III, but not collagen I, were present in these noduli in substantial amounts. These initial studies provide evidence that the changes in the glomerular matrix in diabetic nephropathy may be divided into distinct and progressing stages of lesions. The reduced amount of HSPG even in slight, early lesions may represent the morphologic correlate to the impaired filter function of the glomerular basement membrane. PMID- 1928304 TI - Cytokine influence on simian immunodeficiency virus replication within primary macrophages. TNF-alpha, but not GMCSF, enhances viral replication on a per-cell basis. AB - The control of HIV-1 or SIV replication within macrophages is probably influenced by a variety of viral and cellular factors. Of the cellular factors, the authors have studied cytokine influence on SIV replication in vitro utilizing simian alveolar macrophages and uncloned SIVmacMTV, a macrophage-tropic variant. The approach allowed quantification of viral replication on a per-cell basis. As reported for HIV-1 replication in macrophages, TNF-alpha significantly increased SIV production in these macrophage cultures. GMCSF also resulted in marked increases in SIV gag protein in culture supernatants. However, after correcting for differences in total cell numbers and numbers of gag-containing cells in the treated and untreated cultures, GMCSF did not upregulate SIV production on a per cell basis. IL-6 increased SIV replication little if at all but induced significantly greater cytopathic changes in the treated cultures compared with infected, untreated cultures. In contrast, IFN-gamma greatly decreased replication. Our results for GMCSF, IFN-gamma, and IL-6 are in contrast to previously published reports of cytokine control of HIV-1 growth in target cells, and they stress the importance of cell number analyses and the use of primary cultures in the study of lentiviral replication kinetics in macrophages. PMID- 1928306 TI - Hyperthermia stimulates plasminogen activator inhibitor type 1 expression in human umbilical vein endothelial cells in vitro. AB - The effect of exposure to hyperthermia on the fibrinolytic potential of human umbilical vein endothelial cells (HUVEC) in culture was studied. HUVEC responded to exposure to 42 degrees C with a time-dependent increase in plasminogen activator inhibitor type 1 (PAI-1) activity and antigen accompanied by a four- to fivefold increase in PAI-1 specific m-RNA and a decrease in tissue-type plasminogen activator (t-PA) antigen. The effect of 8 hours exposure to hyperthermia on PAI-1 activity and antigen could not be reversed by reexposure of the cells to 37 degrees C for 24 hours as evidenced by continuously increased amounts of PAI-1 released into the conditioned media. t-PA release, however, decreased during the 24-hour period at 37 degrees C after exposure to hyperthermia. No difference in PAI-1 antigen present in the extracellular matrix of heat treated HUVEC as compared to HUVEC kept at 37 degrees C could be found. Our data supports the idea that hyperthermia is one stress factor that influences the fibrinolytic potential of endothelial cells. PMID- 1928307 TI - Streptococcal cell wall-induced systemic disease. Beneficial effects of trans bis(5-amidino-2-benzimidazolyl)ethene, a novel, macrophage-directed anti inflammatory agent. AB - Previously bis(5-amidino-2-benzimidazolyl)methane (BABIM) was identified as a strong inhibitor of the multisystem inflammatory disease induced in Lewis rats by injection of streptococcus group A cell wall-derived peptidoglycan polysaccharide (PG-APS). A BABIM derivative, trans-bis(5-amidino-2-benzimidazolyl)ethene (BBE), has attracted attention because of striking qualitative and quantitative differences in its activities when compared with the parent compound. BBE could control destructive tibial osteitis and necrotizing granulomatous splenitis and hepatitis, regardless if given in a preventive or curative mode. The compound had little effect on synovitis, however. BABIM, on the other hand, was active against synovitis and osteitis, but not against splenic granuloma formation. To be effective, it needed to be applied in a preventive mode. BBE caused a characteristic enlargement of PG-APS-laden splenic and hepatic macrophages suggesting that those cells represent targets of the inhibitor. BBE may be a powerful tool for the study of granulomatous lesions. PMID- 1928308 TI - Modulation of mesangial cell proliferation by endothelial cells in coculture. AB - The effects of direct cell contact between endothelial (ECs) and mesangial cells (MCs) on MCs proliferation were examined in a coculture system in vitro. Mitomycin C treated ECs (M-ECs) were plated on culture dishes and MCs were cocultured with these M-ECs. Cell number was measured at the end of days 1, 3, and 5. In the coculture system with direct contact, the growth of cocultured MCs was modulated as follows: 1) the growth of MCs was inhibited up to day 3, and 2) a high level of proliferation was observed between days 3 and 5. This biphasic pattern of growth could not be detected in coculture of fibroblasts with MCs. In coculture without direct contact, using intercup chambers, the kinetics in cell proliferation between cocultured MCs and MCs alone were essentially the same. Conditioned media derived from cocultures up to day 3 in a contact-dependent manner inhibited the 3H-thymidine uptake of MCs. From these results, it would thus appear that MCs proliferation is regulated by intercellular contact with ECs. PMID- 1928309 TI - Cochlear implant histopathology. AB - Twenty-two temporal bones and one brain stem from 13 cochlear implant patients were examined histologically. Sixteen temporal bones had undergone one or more implant procedure. Results of analysis suggested that the ganglion cells were the responding elements to the implant and that useful auditory sensation could result from as few as 10 percent of the normal number of ganglion cells. All implanted bones exhibited varying amounts of fibrosis (some ossified) in the basal turn of the cochlea and beyond in some cases. Usually there was damage to the surviving elements of the organ of Corti and the dendrites throughout the extent of the electrode insertion. However, the ganglion cell population was not affected. Prolonged electrical stimulation (up to 14 years) did not affect ganglion cell survival in three cases, and had no effect on the cochlear nerves in two cases or on cochlear nuclei in one case. PMID- 1928310 TI - A comparison of facial nerve monitoring systems in cerebellopontine angle surgery. PMID- 1928312 TI - Degenerative joint disease in hunter-gatherers and agriculturalists from the Southeastern United States. AB - This study examines degenerative joint disease of the major appendicular joints in hunter-gatherers and agriculturalists from northwestern Alabama. Arthritis is highest at the shoulder, elbow, and knee and lower at the hip and ankle. There are virtually no sex differences in the hunter-gatherer group, but in the agriculturalists, males have more severe osteoarthritis than females. The hunters gatherers have a somewhat greater prevalence of arthritis than the agriculturalists, but the differences are rarely significant. The similarity in osteoarthritis levels over time conflicts with biomechanical evidence, which indicates an increase in usual activities in the agricultural period. Several possible reasons for this are explored, including the suggestion that arthritis is a response to intensive or infrequent activities. Whatever the cause, it is clear that biomechanical data and osteoarthritis are responding to different factors and do not equally represent the level of usual activities. PMID- 1928311 TI - Temporomandibular joint osteoarthritis in a British skeletal population. AB - The potential role of dental function in TMJ osteoarthritis is examined in an ancient British population. Human skeletal remains from five archaeological sites in England (n = 369) were studied to assess the associations between the presence of osteoarthritis and dental function variables, in particular antemortem tooth loss and dental attrition. Individuals aged over 17 years with at least a portion of either the left or right TMJ were included in the study. Each individual was scored for the occurrence of arthritic lesions on the mandibular condyle and glenoid fossa, the level of dental attrition, and antemortem tooth loss. A loglinear analysis was performed with osteoarthritis as the dependent variable and tooth loss, attrition, sex, and age as the independent variables. Tooth loss and sex are not significantly associated with TMJ osteoarthritis when attrition and age are included in the analysis. Attrition is significantly associated with osteoarthritis even when the analysis corrects for age. The significant association of attrition with osteoarthritis suggests that dental functions may have an influence, separate from ageing, on the development of TMJ osteoarthritis. PMID- 1928313 TI - Fertility-related changes in maternal body composition among the Au of Papua New Guinea. AB - Evolutionary theory predicts that organisms make trade-offs between their somatic and reproductive energy budgets. Thus every round of reproduction should result in a concomitant decline in the parents' total energy reserves. Among humans this prediction was corroborated more than 25 years ago when fertility-related nutritional depletion was reported among mothers in the Highlands of New Guinea (Jelliffe and Maddocks, 1964). More recently, however, a number of studies of fertility and maternal nutritional status in both developed and developing nations have reported fertility-related increases in various indices of adiposity and lean body mass. Such findings have called the so-called "maternal depletion syndrome" into question, and have raised serious doubts as to whether the phenomenon is widely generalizable to all populations. In light of this recent controversy, data are presented here on fertility-related changes in maternal adiposity and lean body mass among the Au, a lowland forager-horticulturalist population in Papua New Guinea. While both a short-term decline in adiposity following childbirth, and a long-term fertility-related decline are seen among more traditional Au, individuals with a regular source of wage-income show only the former. There are no significant changes in lean body mass with increasing fertility in either group. The finding of significant socioeconomic variation in the capacity to withstand the stress of repeated reproduction even within this one extremely rural area of Papua New Guinea may lend insight into why previous studies have been unable to find evidence of maternal depletion. The fertility related decline in adiposity that is reported for the more traditional Au is consistent with the predictions of evolutionary theory. PMID- 1928314 TI - Some comments on coordinate-free and scale-invariant methods in morphometrics. AB - The unusual strategy for comparing biological shapes is to use some kind of superimposition of the two forms under study and then look at the "residuals" as the shape change. In this paper, I take a careful look at this general strategy and point out some subtle but inherent and important pitfalls. Additionally an alternative approach based on Euclidean Distance Matrix representation is presented. It is applicable to two- as well as three-dimensional objects. PMID- 1928315 TI - Variation in human nasal height and breadth. AB - It has been suggested that the long-standing association of variability in the human nasal index [100 x (nasal breadth)/(nasal height)] with climatic variation is spurious evidence for natural selection in humans (Hoyme, 1965; St. Hoyme and Iscan, 1989). The argument is based principally on the observation that nasal height is globally more variable than nasal breadth, with nasal breadth thus contributing little to variation in the index. This argument does not take into account the confounding effect of absolute size of these variables on their variances. In this study we compare the intrinsic variation in skeletal nasal height and breadth within and among 26 mixed-sex populations (N = 2,408) at globally diverse localities (Howells, 1989), using 2 x 2 variance-covariance matrices of the logarithmically transformed variates. Hypothesis tests for homogeneity of matrices and equal-variance/equal-covariance indicate that the intrinsic variation in nasal breadth is greater than that for nasal height within populations, and that nasal breadth and nasal height exhibit equivalent intrinsic variation among populations. The argument that nasal breadth contributes little to the world-wide variation in the human nasal index is rejected. Given our present understanding of nasal physiological morpho-function, these results support, but do not demonstrate, an adaptive role for human nasal index variation. Promising methods for elucidating natural selection on human nasal form are suggested. PMID- 1928316 TI - Qualitative dermatoglyphic traits as measures of population distance. AB - Thirteen Iranian populations of diverse origin have been analyzed for qualitative dermatoglyphic features utilizing bilateral finger and palmar prints of 3,158 individuals. Bimanual differences were significant for some of the features examined, whereas sex differences were frequently nonsignificant. Interpopulational variation displayed significant heterogeneity for all of the features studied. Distance analysis and constructed dendrograms provided separation between populations in agreement with known ethnohistoric records for hypothenar triradii, and for palmar and finger patterns, but not for the terminations of the D-Line. PMID- 1928317 TI - Premaxillary-maxillary suture fusion and anterior nasal tubercle morphology in the chimpanzee. AB - The anterior nasal spine (ANS) is considered by some to be a unique characteristic of modern humans; however, it has been reported to occur in chimpanzees. Among human populations, ANS size correlates with facial prognathism and timing of premaxillary-maxillary sutural fusion, which may have implications for models of midfacial growth. To investigate these questions, skulls from 55 chimpanzees (Pan troglodytes) (29 male, 26 female), ranging in age from infants to adults, were examined. None of the 55 specimens examined had a true ANS, but a number of specimens exhibited raised anterior nasal prominences or tubercles (ANT) on the nasal surface of the premaxilla. Female specimens had significantly (P less than .05) more ANTs and more extensive fusion of both the palatal and facial components of the suture than did the male specimens. Results from the present study document the presence of an ANT in a sample of chimpanzee crania and are consonant with associations predicted by a septal-traction model of midfacial growth. PMID- 1928319 TI - Paleoepidemiological inference and Neanderthal dental enamel hypoplasias: a reply to Neiburger. PMID- 1928318 TI - Brief communication: coracoclavicular joint in Northwest Indians. AB - The incidence of an articular facet on the conoid tubercle of the clavicle indicating the presence of a coracoclavicular joint was studied in paired clavicles obtained from 1,000 adult subjects aged 18 to 95 years (748 males, 252 females), and 75 children (45 males, 30 females) of known age on whom a medicolegal postmortem had been performed by the second author during 1972-90. The subjects were inhabitants of northwest India. In addition, paired clavicles from 50 neonates and 35 fetuses were also examined. The facet was absent in the fetuses, neonates, and young children. The youngest clavicle showing the facet was from a girl of 13 years, in which it was present bilaterally. In adults the incidence of the facet was 10.1% (bilateral 5.7%, unilateral 4.4%) in males and 8.3% (bilateral 3.6%, unilateral 4.8%) in females. Absence of the facet in the fetuses, neonates, and young children shows that it is not a congenital anomaly. PMID- 1928320 TI - Epithelial ion transport in the fetal and perinatal lung. AB - The lung is a complex organ whose intrauterine development depends on many factors, one of which is a continuous secretion of large volumes of Cl(-) enriched fluid by the pulmonary epithelium. At birth this fluid must be cleared, and it is now known that this process depends in large part on active Na+ transport by the pulmonary epithelium. Only recently has it been possible to culture some of the different lung epithelial cells so that it is possible to investigate the role of individual epithelial cell types, their individual cellular transport mechanisms, and how these are affected by developmental lung maturity. PMID- 1928321 TI - Carbonic anhydrase and chemoreception in the cat carotid body. AB - To test the hypothesis that CO2 and O2 chemoreception in the carotid body (CB) may depend on its carbonic anhydrase (CA) activity, we used an in vitro cat CB preparation and studied the effects of methazolamide, a permeable CA inhibitor (pK 7.3), on the chemosensory responses to CO2, O2, and nicotine. The isolated CB was perfused and superfused with Tyrode solution, free of CO2-HCO3-, at 36.0 +/- 0.5 degrees C. The frequency of chemosensory discharges was recorded from the whole carotid sinus nerve. The responses to bolus injections (0.3-0.5 ml) of Tyrode solution equilibrated with PCO2 of 38-110 Torr, switching from HEPES to CO2-HCO3- Tyrode (PCO2 = 25-60 Torr) for about 3 min, hypoxic Tyrode (PO2 = 25-30 Torr) for 2-8 min, perfusate flow interruptions for approximately 4 min, and bolus injections of nicotine (4 nmol) were studied before, during, and after perfusion (30-45 min) with methazolamide (42.4 microM). Methazolamide reversibly inhibited, delayed, and reduced the responses to transient CO2 stimulus, diminished the onset of but not the late response to prolonged CO2 stimulus, and delayed but did not decrease the responses to hypoxia and perfusate interruption. The response to nicotine did not change. The results indicated that CA in the glomus cells played a crucial role primarily in the speed and magnitude of the initial response to CO2 stimulus and indirectly influenced O2 chemoreception. These effects were upstream from the nicotine receptor-mediated sensory response. PMID- 1928322 TI - Internal and external TEA block in single cloned K+ channels. AB - Tetraethylammonium (TEA) has been used recently to probe natural and mutational variants of voltage-dependent K+ channels encoded by cDNA clones. Its usefulness as a probe of channel structure prompted us to examine the molecular mechanism by which TEA blocks single-channel currents in Xenopus oocytes expressing the rat brain K+ channel, RCK2. TEA at the intracellular surface of membrane patches decreased channel open time and increased the duration of closed intervals. Tetrapentylammonium had similar but more potent effects. Extracellular application of TEA caused an apparent reduction of single-channel amplitude. Block was slower at the high-affinity internal site than at the low-affinity external site. Internal TEA selectively blocks open K+ channels, and the voltage dependence of the block indicates that the binding site lies within the membrane electric field at a point 25% of the distance from the cytoplasmic margin. External TEA also interacts with the open channel but is less sensitive to membrane potential. The results indicate that the internal and external TEA binding sites define the inner and outer margins of the aqueous pore. PMID- 1928323 TI - Inhibition of ion conductances by osmotic shrinkage of Madin-Darby canine kidney cells. AB - Osmotic swelling of Madin-Darby canine kidney (MDCK) cells enhances the ion conductances of the cell membrane, which allows release of cellular ions and subsequent regulatory cell volume decrease. The present study has been performed to test whether cell shrinkage similarly affects the ion conductances of MDCK cell membranes. Increase of extracellular osmolarity by addition of 50 mM NaCl or 100 mM mannitol leads within 3 min to a hyperpolarization of the cell membrane, a marked increase of cell membrane resistance [by 223 +/- 38% (n = 8) and 228 +/- 21% (n = 5), respectively], as well as a moderate increase of the K+ selectivity of the cell membrane (by 37 +/- 13%, n = 9). Thus exposure to hypertonic extracellular fluid decreases the cell membrane conductances including the K+ conductance. Cell volume measurements reveal a regulatory cell volume increase, which is sensitive to both furosemide and dimethylamiloride. Extracellular ATP (10 microM), which activates calcium-sensitive K+ channels, hyperpolarizes the cell membrane close to the K+ equilibrium potential. The respective values are 69.9 +/- 3.1 mV (n = 9) in isotonic fluid, -79.4 +/- 1.8 mV (n = 9) within 3 min, and -76.4 +/- 1.8 mV (n = 7) within 16-h exposure to hypertonic extracellular fluid. This observation points to a sustained increase of intracellular K+ activity after exposure to hypertonic extracellular fluid. PMID- 1928324 TI - Effects of phenylarsine oxide on insulin-stimulated system A amino acid uptake in skeletal muscle. AB - The role of vicinal sulfhydryls in the stimulation by insulin of system A amino acid uptake in mammalian skeletal muscle was investigated. Neutral amino acid uptake via system A carriers was assessed using the nonmetabolizable analogue alpha-(methylamino)isobutyric acid (MeAIB). Phenylarsine oxide (PAO), a trivalent arsenical that interacts with vicinal sulfhydryls, at 40 microM inhibited basal and insulin-stimulated (2 mU/ml) MeAIB uptake in rat epitrochlearis muscles by approximately 50% and approximately 80%, respectively. No significant changes in the ATP level or in the lactate-to-pyruvate ratio were observed. Both inhibitory effects were completely preventable by coincubation with dimercaptopropanol, a vicinal dithiol, indicating the effects were mediated specifically by interactions with vicinal sulfhydryls. Stimulation of MeAIB uptake by the insulin mimicker vanadate (10 mM) or by insulin-like growth factor I (IGF-I, 20 nM) was also inhibited by 80-90% by PAO. Kinetic analysis showed that PAO decreased the apparent Vmax for basal and insulin-stimulated MeAIB uptake without altering the apparent Km. MeAIB uptake already maximally stimulated by insulin was rapidly (half-time = approximately 10 min) reversed by the addition of PAO so that the rate of MeAIB uptake was the same as in muscles incubated throughout with insulin and PAO. These results implicate a major role for vicinal sulfhydryls in the stimulation by insulin of amino acid uptake via system A carriers in skeletal muscle and suggest that the site of action of PAO on this system is distal to the insulin receptor, possibly at the carrier molecule itself. PMID- 1928325 TI - Optical measurements of the dependence of chemoreception on oxygen pressure in the cat carotid body. AB - The relationship between oxygen pressure (PO2) in the carotid body and carotid sinus nerve discharge was evaluated in the isolated perfused/superfused cat carotid body using the oxygen-dependent quenching of phosphorescence. Images of phosphorescence intensity arising from Pd-coproporphyrin within the microcirculation of the carotid body provided measurements of intravascular PO2. These measurements were substantiated by determining phosphorescence life-time. The carotid body was perfused in the isolated state via the common carotid artery with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered Tyrode solution, pH 7.4, at a constant pressure of 80 mmHg. Superfusion was maintained with similar media equilibrated with 100% argon. PO2 in the exchange vessels was markedly less than that in the perfusate entering the carotid artery, 23 +/- 3 and 45 +/- 3 Torr for normoxic (111 +/- 15 Torr) and hyperoxic (345 +/- 72 Torr) perfusates, respectively. Chemosensory discharge rose slowly in response to a brief interruption of perfusate flow as PO2 steadily declined from either of these capillary PO2 values to approximately 10 Torr. Between approximately 10 and 3 Torr, chemosensory discharge increased strikingly, concomitant with an enhanced rate of oxygen disappearance, from -36 +/- 4 to -69 +/- 13 (92% change) and -28 +/- 3 to -48 +/- 3 (71% change) Torr/s for normoxic and hyperoxic perfusates, respectively. As PO2 fell below approximately 3 Torr, oxygen disappearance slowed and neural activity decayed. Thus the relationships between microvascular PO2 and chemosensory discharge and between oxygen disappearance and neural discharge suggest that oxygen metabolism in the carotid body determines the expression of oxygen chemoreception. PMID- 1928326 TI - HETEs and coronary artery endothelial cells: metabolic and functional interactions. AB - Porcine coronary artery endothelial cells have been established in culture. These cells produce prostaglandin (PG) I2, PGF2 alpha, and PGE2 when exposed to either arachidonic acid or ionophore A23187. PG formation was reduced when the cells were exposed to monohydroxy and dihydroxy unsaturated fatty acids. Although all of the hydroxyeicosatetraenoic acids (HETEs) produced reductions, 5-HETE caused the largest decrease in PGI2 formation. Therefore, these lipoxygenase products, especially 5-HETE, may impair the nonthrombogenic surface and some vasodilator responses of coronary endothelium. The cells took up each of the HETEs and incorporated them into phospholipids. Uptake was not affected by equimolar amounts of oleic or linoleic acids; even arachidonic acid reduced 12- and 15-HETE uptake by only 50-60%. Like other cells, the coronary endothelium converted 12- and 15-HETE to polar metabolites. As opposed to other cells, however, these cultures also converted 5-HETE to a more polar metabolite. Thus coronary artery endothelium can take up and metabolize all of the major HETEs, including 5-HETE, and thereby reduce their potentially injurious effects in the coronary circulation. PMID- 1928327 TI - Inhibition of phorbol ester-induced contraction by calmodulin antagonists in rat aorta. AB - The purpose of the present study was to investigate the relative roles of protein kinase C (PKC) and myosin light chain kinase (MLCK) in phorbol ester-induced contraction of vascular smooth muscle through the use of PKC and calmodulin antagonists. Prior exposure to PKC antagonists staurosporine (0.03 microM) and H 7 (10 microM) had relatively little effect on contractions to phorbol 12 myristate 13-acetate (PMA), while contractions to norepinephrine and KCl were greatly inhibited. Prior exposure to the calmodulin antagonists calmidazolium (3 and 10 microM) and W-7 (10 microM) inhibited contractions to PMA in the presence and absence of extracellular Ca2+, while contractions to norepinephrine and KCl remained relatively unaffected. Calmidazolium and W-7 were relatively weak relaxants when applied during the PMA contraction, and the magnitudes of relaxation were similar to those observed in norepinephrine- and KCl-contracted tissues. Calmidazolium partially inhibited the PMA-induced translocation of PKC. These results suggest that 1) the calmodulin antagonists inhibit the development of PMA-induced contraction, at least in part, through inhibition of PKC translocation; 2) the mechanisms of phorbol ester- and agonist-induced translocation of PKC are distinct; 3) the potencies and inhibitory mechanisms of these agents depend on whether the agents are added before or during the contraction; and 4) the selectivity of these agents, as evaluated in enzyme preparations, may not be consistent with their cellular actions. PMID- 1928328 TI - Norepinephrine increases Na-Ca exchange in rabbit abdominal aorta. AB - Na-Ca exchange was measured as intracellular Na+ (Na+i)-dependent 45Ca uptake in rabbit abdominal aortic rings. The amount of Na+i-dependent 45Ca uptake was proportional to both the concentration of Na+ in the Na(+)-loading solution and the concentration of Ca2+ in the assay medium. Na+i-dependent 45Ca uptake was inhibited by incorporation of Na+ in the assay medium and by amiloride analogues. Norepinephrine significantly enhanced the rate of 45Ca uptake in Na(+)-loaded tissue but had no effect on Na+i-independent 45Ca uptake. The effect of norepinephrine was prevented by phentolamine but not by propranolol. The stimulatory effect of norepinephrine was absent when the concentration of extracellular Ca2+(Ca2+o) was 0.3 mM or lower but became significant at 0.6 mM and higher. Na-Ca exchange was also increased by phorbol 12,13-dibutyrate but not by its inactive analogue (4 alpha-phorbol 12,13-didecanoate). 1-(5 Isoquinolinylsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, blocked the stimulatory effect of norepinephrine on Na-Ca exchange. It is suggested that alpha-adrenoceptor stimulation increases Na-Ca exchange in rabbit abdominal aorta in a Na+i- and Ca2+o-dependent fashion. This effect is possibly mediated through the activation of protein kinase C. PMID- 1928329 TI - Muscle-specific regulation of the heme biosynthetic enzyme 5'-aminolevulinate synthase. AB - The induction of 5'-aminolevulinate synthase (ALV synthase) activity in adult muscle by overload occurs in the absence of proportional changes in its mRNA content. Complete interpretation of these findings is difficult because little is known of the basal regulation of ALV synthase expression in muscle. In three adult chicken muscle fiber types (n = 5 each), differences in ALV synthase activity were correlated (r greater than or equal to 0.89; P less than 0.05) to the activities of cytochrome oxidase (COX) and citrate synthase (CS) and to levels of the "liver" isoform of ALV synthase mRNA. During posthatch development, ALV synthase activity and mRNA levels (n = 3-6 per time point) also covaried with changes in COX and CS activity. The highest levels of ALV synthase mRNA in muscle are observed early in myogenesis prior to induction of COX activity. The regulation of ALV synthase is also tissue-specific because the higher basal levels of ALV synthase activity in liver mitochondria are associated with disproportionately less oxidative enzyme activity and less of the liver ALV synthase isoform mRNA than in muscle. PMID- 1928330 TI - A replica filter assay for expression of ion transport proteins. AB - In thyroid cells, iodide is accumulated intracellularly via a Na+-I cotransporter. In this report we show that it is possible to detect diffusible 125I-concentrated in thyroid cell colonies that have been replicated onto nylon filters. Using the replica filter assay, we demonstrate that the iodide transport 1) is restricted to thyroid cells, 2) is Na+ dependent and electrogenic, 3) is inhibited by ClO4- and SCN-, and 4) is adenosine 3',5'-cyclic monophosphate dependent. These are all characteristics of thyroidal iodide transport. This technique can, in principle, detect the expression of any transport system that results in the intracellular accumulation of a diffusible molecule. Moreover, the filter assay can be used to screen for colonies carrying structural or functional mutations affecting such transport systems. PMID- 1928331 TI - Reconstitution of isolated Ca(2+)-activated K+ channel proteins from basolateral membranes of rabbit colonocytes. AB - Using calmodulin-affinity chromatography, we have isolated a fraction of proteins from solubilized basolateral membranes of rabbit colonocytes which when reconstituted into planar phospholipid bilayers disclosed Ca(2+)-activated single K+ channel activities. The properties of the reconstituted channels are identical to those of native membrane vesicles incorporated into these bilayers with respect to their high selectivity for K+ over C-, high ("maxi") conductance, voltage gating, and inhibition by trifluoperazine. Two-dimensional sodium dodecyl sulfate gel electrophoresis of these proteins revealed three major protein species with molecular masses of 120, 60, and 35 kDa, which constituted 70, 10, and 20%, respectively, of the total protein. The results of other studies strongly suggest that the 35-kDa protein may be the Ca(2+)-activated K+ channel protein in these membranes. PMID- 1928332 TI - Sodium current and membrane potential in EDL muscle fibers from normal and dystrophic (mdx) mice. AB - The macroscopic and single-channel properties of sodium currents and membrane potential were studied in intact extensor digitorum longus (EDL) muscle fibers from mdx (C57BL/10ScSn-mdx) and normal (C57BL/10SnJ) mice. The voltage dependence of activation and inactivation were determined and the associated gating charges were calculated to determine if the lack of dystrophin associated with the mdx condition has any influence on sodium channels either directly or by effects on the membrane environment of the channel. Sodium currents were recorded from cell attached patches on EDL muscle fibers isolated by collagenase treatment and manual dissection. Both macroscopic and single-channel currents were studied. We found no apparent difference in the sodium channel properties from the two types of muscle. In addition, microelectrode measurements in both mdx and normal muscle fibers indicated similar resting membrane potentials (Vm around -95 mV), which suggests that the normal behavior of sodium channels in the muscle sarcolemma is unaffected by the X-linked gene defect. PMID- 1928333 TI - Arterial catecholamine responses during exercise with acute and chronic high altitude exposure. AB - Exercise at high altitude is a stress that activates the sympathoadrenal systems, which could affect responses to acute altitude exposure and promote adaptations during chronic altitude exposure. However, catecholamine levels are not clearly described over time at high altitude. In seven male volunteers (23 yr, 72 kg), resting arterial norepinephrine concentrations (ng/ml) on arrival at Pikes Peak (0.338 +/- 0.041) decreased compared with sea-level values (0.525 +/- 0.034) but increased to above sea-level values after 21 days at 4,300 m (0.798 +/- 0.052). Furthermore, during 45 min of constant submaximal exercise, values were similar at sea level (1.670 +/- 0.221) and on acute exposure to 4,300 m (2.123 +/- 0.086) but increased after 21 days of chronic exposure (2.693 +/- 0.216). By contrast, resting arterial epinephrine values (ng/ml) during acute and chronic exposure (0.708 +/- 0.033 vs. 0.448 +/- 0.026) both exceeded those of sea level (0.356 +/- 0.020). During exercise values on arrival were greater than at sea level (0.921 +/- 0.024 vs. 0.397 +/- 0.035) but fell to 0.612 +/- 0.025 ng/ml after 21 days. Exercise norepinephrine levels were related to systemic vascular resistance measurements (r = 0.93), whereas epinephrine levels were related to circulating lactate (r = 0.95). We conclude that during exercise at altitude there is a dissociation between norepinephrine, an indicator of sympathetic neural activity, and epinephrine, an indicator of adrenal medullary response. These actions may account for different metabolic and physiological responses to acute vs. chronic altitude exposure. PMID- 1928334 TI - In vivo evidence for hepatic autoregulation during FFA-stimulated gluconeogenesis in normal humans. AB - To examine the effect of increased gluconeogenesis [by increasing free fatty acids (FFA)] on hepatic glucose output (HGO) and on the first substrate (glucose) cycle, a primed continuous infusion of [2-3H]- and [6-14C]glucose was infused to isotopic steady state in 12 normal male volunteers after an overnight fast. Blood samples for the determination of glucose specific activity were obtained before and after an infusion of saline (n = 6) or 10% Intralipid and heparin (90 mU.kg 1.min-1, n = 6). Plasma FFA (593.3 +/- 74.5 to 971.1 +/- 127.1 mumol/l, P = 0.007) and glycerol (68.0 +/- 5.9 vs. 222.4 +/- 32.0 mumol/l, P = 0.002) increased during the lipid infusion, and beta-hydroxybutyrate levels rose from 0.24 +/- 0.12 to 0.50 +/- 0.17 mmol/l (P = 0.01). No change in plasma glucose, insulin, or glucagon levels was observed during the study, and levels of the gluconeogenic substrates alanine and lactate were also unchanged. Baseline rates of glucose cycling (rate of appearance of [2-3H]glucose minus rate of appearance of [6-14C]glucose) were similar in the two groups [1.44 +/- 0.33 vs. 1.33 +/- 0.44 mumol.kg-1.min-1, not significant (NS)] and did not change during either saline or lipid infusion, respectively. However, Cori cycle activity (the conversion of [6-14C]- to [1-14C]glucose) increased significantly from 0.59 +/- 0.19 to 1.28 +/- 0.19 mumol.kg-1.min-1 (P = 0.002) after FFA and glycerol levels had been increased, in marked contrast to the saline control (0.51 +/- 0.18 to 0.39 +/- 0.18 mumol.kg-1.min-1, NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928335 TI - Cephalic phase insulin release in normal weight males: verification and reliability. AB - The existence and reliability of cephalic phase insulin release (CPIR) were tested in 20 normal weight males. Each subject was challenged three times with the same food stimulus over a 5-day period. Four baseline blood samples were taken at 5-min intervals before food ingestion and then every 2 min for 16 min postingestion. Significant increases in plasma insulin were found at 4 min postingestion on each trial day. CPIR was found to be highly reproducible between trials (r = 0.83; P less than 0.001). Fifty percent of the subjects exhibited a significant increase of plasma insulin above their own baseline mean on the first trial, whereas 75 and 72% exhibited increases on trials 2 and 3, respectively. Only two subjects (10%) did not demonstrate a response on any trial. A significant decline in plasma glucose was observed at 4 min postingestion on trials 2 and 3. No significant changes in plasma glucagon were found during any trial day. This study confirms a reliable CPIR in normal weight males. PMID- 1928336 TI - Elevated skeletal muscle glucose transporter levels in exercise-trained middle aged men. AB - Exercise training has been proposed to improve whole body insulin sensitivity through a postreceptor adaptation in skeletal muscle. This study examined if levels of the insulin-responsive muscle glucose transporter protein (GLUT-4) were associated with improved insulin sensitivity in trained vs. sedentary middle-aged individuals. Muscle GLUT-4 levels and oral glucose tolerance test (OGTT) responses were obtained in age-matched trained and sedentary men (n = 11). Plasma insulin levels during the OGTT were significantly lower (P less than 0.01) in the trained men, whereas no differences were seen in plasma glucose responses. GLUT-4 protein content was approximately twofold higher in the trained men (2.41 +/- 0.17 vs. 1.36 +/- 0.11 micrograms standard, P less than 0.001). OGTT responses and GLUT-4 levels were not altered 15-18 h after a standard exercise bout in six representative sedentary subjects. These data suggest that GLUT-4 levels are increased in conjunction with insulin sensitivity in chronically exercise-trained middle-aged men. This finding suggests a possible mechanism for the improved insulin sensitivity observed with exercise training in humans. PMID- 1928337 TI - Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans. AB - To evaluate the role of tumor necrosis factor (TNF) in the initiation of the metabolic response to acute infection, we performed a crossover saline-controlled study in six healthy postabsorptive men, investigating the metabolic effects of a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced a transient stress hormone response, associated with an early and sustained rise in plasma glucose concentrations (percentage increase at 2 h 23 +/ 7; P less than 0.05). Glucose turnover, measured 7.5 h postinjection, was 10 +/- 3% higher after TNF administration (P less than 0.05). Plasma free fatty acids (FFA) and glycerol concentrations increased transiently after TNF injection, peaking after 4 h (percentage increase 363 +/- 83 and 67 +/- 14, respectively; both P less than 0.05). FFA turnover, determined 6.5 h postinjection, increased in five subjects to a variable extent (percentage increase 126 +/- 55; P less than 0.05). Finally, resting energy expenditure showed a transient rise after TNF injection (34 +/- 2% at 4 h; P less than 0.05). We conclude that intravenous TNF reproduces many of the metabolic changes observed in septicemia, suggesting that TNF may be an initiating factor in the development of the metabolic response to acute infection. PMID- 1928338 TI - Regulation of lipolysis and ketogenesis by norepinephrine in conscious dogs. AB - The lipolytic and ketogenic effects of norepinephrine (NE) at levels present in the circulation or the synaptic cleft during stress were examined in the overnight-fasted conscious dog. Insulin and glucagon were maintained at basal levels while NE, at a rate of either 0.04 (n = 6) or 0.32 micrograms.kg-1.min-1 (n = 5), or saline (n = 6) was infused for 3 h. NE rose from 129 +/- 17 to 442 +/ 85 pg/ml (P less than 0.05) and 100 +/- 24 to 3,244 +/- 807 pg/ml (P less than 0.05) with the low and high infusion rates, respectively (unchanged with saline infusion). There were no significant changes in lipolysis or ketogenesis with saline infusion. Both low and high NE infusion produced sustained increases in glycerol (from 72 +/- 20 to 119 +/- 24 microM and 59 +/- 19 to 248 +/- 32 microM, respectively, both P less than 0.05), while nonesterified fatty acids (NEFA) rose from 609 +/- 85 to 952 +/- 100 and 767 +/- 140 to 2,054 +/- 199 microM (both P less than 0.05). Ketone levels and net hepatic production rose significantly only with the high NE infusion (from 88 +/- 10 to 266 +/- 46 microM and 1.30 +/- 0.26 to 7.62 +/- 1.48 mumol.kg-1.min-1, respectively, both P less than 0.05). The ratio of net hepatic ketone production to NEFA uptake rose 54% with high NE infusion. In conclusion, at circulating levels seen during stress, NE stimulates lipolysis but does not directly influence ketogenesis. At circulating levels projected to exist in the synaptic cleft during stress, NE has a potent lipolytic effect and stimulates ketogenesis. PMID- 1928339 TI - Use of mass isotopomer distributions in secreted lipids to sample lipogenic acetyl-CoA pool in vivo in humans. AB - Measurement of hepatic fatty acid (FA) and cholesterol synthesis has been limited by lack of access to the precursor pool, cytosolic acetyl-CoA. We present a method for inferring the enrichment of the true hepatic lipogenic precursor pool in humans using the frequency distribution of mass isotopomers within enriched circulating polymers of acetyl-CoA [very low-density lipoprotein (VLDL) palmitate, VLDL-stearate]. Human subjects were infused intravenously (n = 16) with [1-13C]- or [2-13C]acetate. Oral sulfamethoxazole (SMX) was administered concurrently, and the acetylated conjugate (SMX acetate) was used to estimate independently the hepatic cytosolic acetyl-CoA enrichment. Isotopomer frequencies in VLDL-FA were determined by gas chromatography-mass spectrometry, whereas high performance liquid chromatography-mass spectrometry was used to measure enrichments in SMX acetate. Based on the excess M2/excess M1 ratio in VLDL-FA, calculated acetyl-CoA enrichments were 5.59 +/- 0.33 molar percent excess (MPE), whereas SMX acetate enrichments were 5.38 +/- 0.31 MPE (the 2 methods were not significantly different). Mass isotopomer-calculated and SMX acetate-measured estimates of acetyl-CoA enrichments correlated very closely in individual subjects (r2 = 0.93; P less than 0.0001). De novo hepatic lipogenesis can be measured using isotopomer-calculated precursor enrichments compared with measured incorporation in specific isotopomers of VLDL-FA. In summary, excess isotopomer frequencies in secreted lipids provide a non-invasive technique for estimating hepatic cytosolic acetyl-CoA enrichments in humans in vivo and correlate closely with enrichments observed using the xenobiotic probe technique. Isotopomeric distributions represent a new strategy for accurate measurement of macromolecule synthesis that may be applicable to other classes of molecules besides lipids. PMID- 1928340 TI - Dissociation in plasma renin and adrenal ANG II and aldosterone responses to sodium restriction in rats. AB - In rats, plasma renin activity (PRA) increases sharply, reaching a plateau within hours of sodium restriction. Plasma aldosterone increases gradually, not reaching a plateau for 1-2 days. To determine whether this dissociation is secondary to the time needed to modify adrenal sensitivity to angiotensin II (ANG II) and to assess the role of locally produced ANG II in this process, rats were salt restricted for 0-120 h. Plasma hormone levels were assessed, adrenal ANG II was measured, and basal and ANG II (1 x 10(-8) M)-stimulated steroidogenesis were determined in vitro. Although PRA attained an elevated plateau within 8 h, plasma aldosterone did not peak until after 48 h of sodium depletion. The in vitro aldosterone sensitivity to exogenous ANG II was not apparent until rats had been salt restricted for 16 h. A plateau (4-fold increase above the ANG II response on high salt) was achieved between 24 and 48 h. Adrenal ANG II also exhibited a similar delayed response that correlates significantly with changes in aldosterone biosynthesis and late pathway activity. Thus the dissociation between PRA and plasma aldosterone may be secondary to a lag in the zona glomerulosa's (ZG) steroidogenic response to ANG II as well as a parallel lag in tissue ANG II production, suggesting that changes in tissue ANG II may mediate ZG sensitivity to ANG II during sodium deprivation. PMID- 1928341 TI - Effect of short-term fasting on the lipolytic response to theophylline. AB - We investigated the hypothesis that the increase in lipolysis that occurs in short-term (86-h) fasting is due to a decreased inhibitory influence of adenosine. In normal volunteers who fasted for 14 and 86 h, the response to adenosine receptor blockade was assessed by the infusion of theophylline at a rate sufficient to produce plasma concentrations (30 microM) that blocked adenosine receptors but that were well below the threshold for inhibition of phosphodiesterase. Lipolysis was assessed by determining the rate of appearance of glycerol using D-5-glycerol infusion. Fatty acid flux was also determined by means of [1-13C]palmitate infusion, and total fatty acid oxidation was determined by indirect calorimetry. There was a mild stimulatory effect of theophylline on lipolysis at 14 h. After the subjects fasted for 86 h, theophylline infusion caused a much greater increase in both lipolysis and fatty acid oxidation. These results suggest that the inhibitory effect of adenosine on lipolysis is increased during short-term fasting. PMID- 1928342 TI - Neuronal uptake, metabolism, and release of tritium-labeled norepinephrine during assessment of its plasma kinetics. AB - The extent to which intravenously infused [3H]norepinephrine ([3H]NE) is stored within and released by sympathetic nerves (tracer recycling) was examined by assessment of its plasma concentrations and by those of its intraneuronal metabolite dihydroxyphenylglycol (DHPG). Tracer recycling, as assessed by perturbations to steady-state plasma [3H]NE, was not apparent in humans during sympathetic activation by orthostasis or exercise. During intense electrical stimulation of cardiac sympathetic nerves after an [3H]NE infusion in dogs, plasma [3H]NE was higher in coronary sinus than arterial plasma, consistent with tracer recycling by cardiac sympathetic nerves. The specific activity of released [3H]NE was similar to that of [3H]NE and [3H]DHPG in cardiac tissue, indicating that both released [3H]NE and [3H]DHPG were derived from the same pool of neuronally stored [3H]NE. During intravenous infusion of [3H]NE in humans, plasma [3H]NE reached a steady state within 12 min and remained constant, whereas plasma [3H]DHPG increased progressively, reflecting metabolism of an increasing amount of [3H]NE leaking from sympathetic vesicles. Plasma concentrations of [3H]DHPG approached or exceeded those of [3H]NE after the end of radiotracer infusions and in the venous drainage of the heart and liver. Thus, to avoid error during assessment of plasma [3H]NE kinetics, an analytical step should be employed to separate plasma [3H]DHPG from [3H]NE. Because [3H]DHPG is derived from [3H]NE within the neuron, the specific activity of neuronally stored [3H]NE could be assumed to be no higher than the specific activity of plasma [3H]DHPG. This provided a means to estimate the maximum extent of tracer recycling, thereby indicating that, during intravenous infusion of [3H]NE, tracer recycling contributed negligibly (less than 5%) to steady-state plasma [3H]NE at normal levels of sympathetic activity. PMID- 1928343 TI - Kinetics of equilibration of radioiodide in individual mouse thyroid follicles in vivo. AB - Microdensitometric measurements were made on autoradiographs of radioiodide localized in mouse thyroids subjected to various degrees of stimulation, in which the formation of organic radioiodide was acutely blocked. Estimates were made of the relative concentrations of radioiodide in lumens and cells of follicles and in the nearby blood vessels. Simple models were introduced to interpret the data. Analysis of the ratio of radioiodide concentrations in the lumen and cells of follicles as a function of follicles size and time after injection indicated that smaller follicles equilibrated faster than larger follicles, that the equilibration was faster the more active the gland was, and that the release of radioiodide from follicles in the less active glands must be characterized by a time-dependent exit rate constant. Analysis of the relative concentration of luminal radioiodide as a function of follicle size at short time intervals and in the steady state indicated that the transport properties of the average epithelial cell were generally independent of follicle size. PMID- 1928344 TI - Compartmental model of leucine kinetics in humans. AB - The complexity of amino acid and protein metabolism has limited the development of comprehensive, accurate whole body kinetic models. For leucine, simplified approaches are in use to measure in vivo leucine fluxes, but their domain of validity is uncertain. We propose here a comprehensive compartmental model of the kinetics of leucine and alpha-ketoisocaproate (KIC) in humans. Data from a multiple-tracer administration were generated with a two-stage (I and II) experiment. Six normal subjects were studied. In experiment I, labeled leucine and KIC were simultaneously injected into plasma. Four plasma leucine and KIC tracer concentration curves and label in the expired CO2 were measured. In experiment II, labeled bicarbonate was injected into plasma, and labeled CO2 in the expired air was measured. Radioactive (L-[1-14C]leucine, [4,5-3H]KIC, [14C]bicarbonate) and stable isotope (L-[1-13C]leucine, [5,5,5-2H3]KIC, [13C]bicarbonate) tracers were employed. The input format was a bolus (impulse) dose in the radioactive case and a constant infusion in the stable isotope case. A number of physiologically based, linear time-invariant compartmental models were proposed and tested against the data. The model finally chosen for leucine KIC kinetics has 10 compartments: 4 for leucine, 3 for KIC, and 3 for bicarbonate. The model is a priori uniquely identifiable, and its parameters were estimated with precision from the five curves of experiment I. The separate assessment of bicarbonate kinetics (experiment II) was shown to be unnecessary. The model defines masses and fluxes of leucine in the organism, in particular its intracellular appearance from protein breakdown, its oxidation, and its incorporation into proteins. An important feature of the model is its ability to estimate leucine oxidation by resolving the bicarbonate model in each individual subject. Finally, the model allows the assessment of the domain of validity of the simpler commonly used models. PMID- 1928345 TI - Potassium transport across basolateral membrane of acinar cells in the perfused rat pancreas. AB - Efflux and influx of K+ across the basolateral membrane of acinar cells were continuously computed from the change in K+ concentration in the perfusate collected from the portal vein of the isolated perfused rat pancreas. Continuous stimulation with different concentrations of COOH-terminal octapeptide of cholecystokinin (CCK-8) caused characteristic patterns of K+ flux and fluid secretion as follows: 1) stimulation with 10 pM CCK-8 induced a gradual and small increase in K+ influx and sustained fluid secretion; 2) stimulation with 100 pM CCK-8 caused an initial transient K+ efflux followed by a secondary slow K+ influx and sustained fluid secretion; 3) stimulation with 1 nM CCK-8 also induced an initial transient K+ efflux followed by a secondary slow K+ influx, whereas there was only a slight transient increase in fluid secretion. Ouabain abolished the CCK-8-induced K+ influx, but furosemide had little, if any, effect on the CCK 8-induced K+ flux and fluid secretion. Complete replacement of Cl- with equimolar NO3- had little effect on the CCK-8-induced K+ influx. These results suggest that CCK-8 activates not only passive K+ transport but also an ouabain sensitive Na(+) K+ pump and that the furosemide-sensitive Na(+)-K(+)-2Cl- symport may not play a significant role in CCK-8-induced K+ transport. PMID- 1928346 TI - Effects of vasopressor hormones and modulators of protein kinase C on glutathione efflux from perfused rat liver. AB - Vasopressor hormones alter efflux of glutathione (GSH) and increase permeability of tight junctions in perfused rat liver. Infusions of 10 nM angiotensin II, 10 microM phenylephrine, and 10 nM vasopressin significantly increased efflux of GSH into perfusate by 32-41% and decreased biliary efflux by 31-57%. Direct modulation of protein kinase C (PKC) activity by 600 nM phorbol 12,13-dibutyrate (PDB), 5 microM 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), 5 microM sphingosine, or 10 nM staurosporine altered the pattern of efflux of GSH but not biliary oxidized glutathione disulfide (GSSG)-GSH ratios. Phorbol dibutyrate mimicked the vasopressor-mediated effects, increasing perfusate efflux by 31% and decreasing biliary efflux by 45%. Inhibitors of PKC caused qualitatively opposite responses, changing perfusate GSH by -37 to 18% and increasing biliary efflux by 22-161%. Whereas vasopressin increased penetration of [14C]sucrose into bile, modulation of PKC activity by PDB and H-7 did not affect the permeability of tight junctions to [14C]sucrose. Although pretreatment with H-7 blocked vasopressin-mediated changes in efflux of GSH, it did not prevent the increase in [14C]sucrose penetrance. We conclude that alterations in sinusoidal and biliary efflux of GSH can occur independent of changes in permeability of hepatocellular tight junctions. These findings suggest a role for protein kinase C in modulating the hepatic efflux of GSH. PMID- 1928347 TI - Altered glucose carrier expression: mechanism of intestinal adaptation during streptozocin-induced diabetes in rats. AB - Intestinal adaptation of glucose transport during streptozocin-induced diabetes in rats was examined using microdensitometric analysis of [3H]phlorizin binding. Results of specific phlorizin binding were correlated with measurements of maximal transport capacity, carrier affinity, villus height, and enterocyte birth rate determined by the metaphase arrest technique. Animals diabetic for 14 days (acute) and 60 days (chronic) were compared with age-matched controls. In the jejunum, adaptation occurred only in chronically diabetic rats and consisted of a 10-fold increase in the density of phlorizin binding sites in the upper villus region (i.e., that portion normally transporting glucose), while in the ileum, adaptation occurred both in acute and chronically diabetic rats and consisted of 1) a 3-fold increase in density of phlorizin binding sites in the upper villus region of acutely diabetic rats and 2) an increased density in the upper villus region as well as the recruitment of phlorizin binding sites in the mid to lower villus region (i.e., that portion not normally transporting glucose) of chronically diabetic rats. Enhancement of glucose Vmax and villus length accompanied changes in binding, whereas enterocyte birth rates were similar in each group. PMID- 1928348 TI - Nutrient extraction by cold-exposed mice: a test of digestive safety margins. AB - We examined the size of the "safety margin," if any, by which the small intestine's daily capacities to absorb nutrients exceed prevailing daily intakes of those nutrients. This safety margin, also known as reserve capacity, is widely assumed to be enormously large. As a test, we suddenly transferred mice from an ambient temperature of 22 to 6 degrees C and measured food intake, apparent digestive efficiency, intestinal morphometrics, and intestinal brush-border uptake capacities for D-glucose and L-proline over the next 28 days. Food intake jumped 68% within the first 12 h and rose in 2 days to a new plateau level 2.5 times the previous intake. Nevertheless, apparent digestive efficiency remained unchanged, even within the first 12 h, and intestinal transit times also remained unchanged, implying the existence of at least some safety margin. Masses of the small and large intestine, liver, kidneys, and spleen nevertheless increased within 4 days by 16-20%. Glucose and proline uptakes per milligram intestine increased by approximately 5%, so that the intestine's summed uptake capacities for these solutes increased by 24-26%. The animal's intestinal adaptation expressed in these increased uptake capacities implies that safety margins at the new plateau value of food intake would otherwise have been dangerously narrow. Comparison of calculated summed uptake capacities with measured dietary intakes suggests that safety margins are approximately 220-300% in mice at 22 degrees C, only 27-50% in mice at 6 degrees C before intestinal adaptation, but 60-88% in mice at 6 degrees C after intestinal adaptation. PMID- 1928349 TI - ATP-dependent control of steady-state cytosolic calcium in cultured gastric smooth muscle. AB - The regulation of intracellular calcium uptake and release in cultured gastric smooth muscle cells was studied in saponin-permeabilized cells derived from the rabbit antrum. Cells were studied in an ATP-regenerating medium in which the value of the ATP-to-ADP ratio was fixed by variation of the relative concentrations of creatine and creatine phosphate in the presence of a constant concentration of adenine nucleotides and creatine kinase. Free calcium in the medium was measured through the use of the fluorescent probe fura-2. As the ratio of ATP/ADP was increased (8.5, 55.0, and 155.0), the rate of calcium sequestration was increased, resulting in a decrease of steady-state free calcium (275.2, 178.4, and 98.1 nM, respectively). The addition of glucose (5 mM) and hexokinase (15 U/ml), which results in an increase of ADP due to the phosphorylation of glucose in the medium, caused an increase of free calcium concentration to a new set point of approximately 400 nM. Mitochondrial blockade with antimycin A before permeabilization had no effect on calcium sequestration or the resultant free calcium concentration, indicating that under physiological conditions calcium is sequestered predominantly into nonmitochondrial storage sites. Specific variation of ATP/ADP had no effect on the concentration dependence of inositol trisphosphate-induced calcium efflux, suggesting the functional independence of intracellular calcium influx and efflux pathways. These results indicate a significant role for cytoplasmic ATP/ADP in the control of intracellular calcium sequestration and the regulation of steady-state calcium concentration in cultured gastrointestinal smooth muscle cells. PMID- 1928350 TI - Lipoprotein lipase enables triacylglycerol hydrolysis by perfused newborn rat liver. AB - Fasted 1-day-old rat liver has high heparin-releasable (endothelial) lipoprotein lipase (LPL) activity, and its hepatocytes synthesize LPL protein. To test the physiological role of this LPL, we perfused the isolated organ with a 0.8 mM triacylglycerol (TAG) (Intralipid + glycerol tri[3H]oleate) 6.3% serum medium. Samples of the recirculated perfusate were taken at different times to determine 3H in TAG, free fatty acid (FFA), and water-soluble (WS) fractions. In the medium [3H]TAG disappeared and [3H]FFA and [3H]WS fractions appeared linearly with time. This TAG hydrolysis was 1) absent when medium was recirculated without liver, 2) not affected by chloroquine addition, 3) inhibited by anti-LPL immunoglobulins, 4) absent when serum was omitted from the medium, and 5) restituted when apolipoprotein CII was added to the medium without serum. Therefore, lysosomal lipase is not involved in this TAG hydrolysis, the features of which are characteristic of LPL, not of the so-called "hepatic endothelial lipase." Thus LPL activity enables the neonatal rat liver to hydrolyze and take up circulating TAG, i.e., has the same function as extrahepatic LPL. PMID- 1928351 TI - Mechanism of changes in hepatic sinusoidal and biliary glutathione efflux with age in rats. AB - To delineate the kinetic mechanism(s) of declining sinusoidal reduced glutathione (GSH) efflux with age, we perfused livers of male rats ages approximately 1-1.5, approximately 2-3, and approximately 3.5-6 mo old and measured sinusoidal and biliary GSH and oxidized glutathione (GSSG) effluxes. Our results showed declining GSH transport to be solely due to a falling maximum transport rate (Vmax) and not an increasing Michaelis constant (Km)(Vmax = 24.2 +/- 2.95, 15.8 +/- 1.51, and 8.61 +/- 0.75 nmol. min-1.g-1; Km = 3.0 +/- 0.42, 2.6 +/- 0.31, and 2.6 +/- 0.43 mumol/g for the three age groups, respectively). Because hepatocyte membrane potential was earlier implicated as a driving force for GSH efflux and hepatocytes of female rats were reported to be less polarized than those of males, we likewise studied the kinetics of sinusoidal GSH efflux from livers of female rats of three age groups comparable to our males. Vmax in females tended to be lower than in males. This was more pronounced in the youngest group but was diminished in the older groups. Vmax was again the only parameter declining with age in the female livers, from 19.1 +/- 2.25 to 15.0 +/- 0.95 and 7.83 +/- 0.99 nmol.min-1.g-1, whereas Km remained unchanged at 3.0 +/- 0.45, 3.1 +/- 0.35, and 3.2 +/- 0.72 mumol/g, respectively. Age-dependent changes in GSH efflux were not due to a changing membrane potential. There was no appreciable change in the paracellular permeability with age either.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928352 TI - Oxygen metabolites stimulate mucous glycoprotein secretion from cultured rat gastric mucous cells. AB - The aims of this study were to investigate the interaction between oxygen radicals and mucus secretion from cultured rat gastric mucous cells, and to assess the role of prostaglandin production in the modulation of mucus secretion in vitro. Xanthine oxidase in the presence of hypoxanthine caused a dose dependent increase in the presence of hypoxanthine caused a dose-dependent increase of mucus secretion, as assessed by release of [3H]glucosamine from prelabeled cells, whereas xanthine oxidase or hypoxanthine alone did not. Xanthine oxidase (10 mU/ml) increased release of [3H]glucosamine by 57 +/- 6% compared with control values (P less than 0.001). Catalase (3,000 U/ml) inhibited xanthine oxidase-induced mucus secretion by 69 +/- 9% (P less than 0.01), whereas superoxide dismutase did not. Pretreatment with deferoxamine, an inhibitor of hydroxyl radical generation through chelating ferric ion, diminished oxygen radical-induced mucus release to control values. Xanthine oxidase dose dependently stimulated prostaglandin E2 (PGE2) production, which was blocked by catalase but not by superoxide dismutase. However, oxygen radical stimulation of mucus secretion was not inhibited by the addition of indomethacin. Moreover, PGE2, exogenously administered, did not significantly accelerate mucus secretion. Stimulation of mucus secretion by oxygen radicals was not accompanied by increased 51Cr release or by leakage of intracellular lactate dehydrogenase. These results suggest that oxygen species, particularly hydroxyl radical, stimulate mucous glycoprotein secretion from cultured rat gastric mucous cells. However, it seems unlikely that prostaglandin production mediates the oxygen species-induced stimulation of mucus secretion. PMID- 1928353 TI - Topography of the esophageal peristaltic pressure wave. AB - Topographic plots constructed from conventional esophageal manometric waves were examined in 12 healthy volunteers to better understand spatial relationships of peristaltic contractions. Typical postdeglutitive waves were spatially interconnected using a computerized gridding and plotting system. Contour plots of the resultant peristaltic contraction revealed a consistent separation of a proximal pressure segment from the prominent distal contraction at 21.7 +/- 1.3% of the esophageal length. A second trough in the contraction sequence was found in 11 (91.7%) of the subjects at 64.0 +/- 2.7% of esophageal length separating the distal (smooth muscle) esophagus into two contraction segments. Similar topographic studies were also performed in eight symptomatic patients with frequent double-peaked waves. Poor alignment of the two distal contraction segments was observed in six (75%) of the eight patients. These topographic plots demonstrate previously unrecognized wave relationships and suggest that two neuromuscular contraction units can be detected in the distal smooth muscle esophagus. This technique should be useful in understanding altered relationships of these units under differing physiological conditions or with disease. PMID- 1928354 TI - Pancreatic microvascular permeability in caerulein-induced acute pancreatitis. AB - Microvascular permeability was studied in the isolated perfused rat pancreas using a rapid multiple indicator-dilution technique. Capillary extractions, permeability-surface area products (PS), and extravascular volumes of distribution (EVV) were determined for 22Na+, 51Cr-labeled EDTA, [57Co] cyanocobalamin (B12), and 125I-labeled insulin at various perfusion flows. Permeability to albumin was negligible. PS for Na+ and EDTA increased with increasing flow, whereas PS for cyanocobalamin and insulin approached diffusion limited exchange at flows greater than 3 ml.min-1.g-1. Permeability coefficients for Na+, EDTA, B12, and insulin were 36, 22, 11, and 3.48 x 10(-5) cm/s, respectively, and the permeability ratio for B12/insulin (3.16) indicated restricted diffusion to insulin. In the presence of unlabeled B12 and insulin EVV (0.15-0.19 ml/g) for EDTA, B12 and insulin approximated the interstitial volume. Caerulein-induced pancreatitis or treatment with the synthetic protease inhibitor camostate had no significant effects on permeability. In caerulein-treated rats, EVV for B12 was elevated (0.17 +/- 0.01 vs. 0.28 +/- 0.06; P less than 0.01), reflecting the interstitial edema associated with this model of pancreatitis. Permeability of the rat pancreatic microvasculature is similar to that of other fenestrated tissues, but it is 10- to 20-fold greater than that of continuous capillaries. Contrary to previous assumptions, permeability does not appear to be increased after induction of acute interstitial pancreatitis. PMID- 1928355 TI - Neuropeptides and nasal secretion. AB - The nasal mucosa is innervated by the sensory, parasympathetic, and sympathetic nervous systems. Nociceptive sensory nerves are stimulated by mucosal injury, inhalation of irritants, or mast cell degranulation and release of the calcitonin gene-related peptide, the tachykinins substance P and neurokinin A, and other peptides by the axon response mechanism. Sensory nerve stimulation initiates systemic reflexes, such as the sneeze, and central parasympathetic reflexes which release acetylcholine, vasoactive intestinal peptide, and other peptides and lead to glandular secretion. In concert, these proinflammatory neural responses lead to vasodilation, vascular permeability, and glandular secretion. Sympathetic nerves release neuropeptide Y and norepinephrine, potent vasoconstrictors which act to decompress the nasal mucosa and produce nasal patency. The balance between the effects of parasympathetic and sympathetic neurotransmitters may regulate nasal homeostasis, whereas the nociceptive sensory system may be held in reserve as a defense mechanism. Dysfunction of these systems may lead to pathological nasal syndromes. In the future, specific neuropeptide agonists and antagonists may be useful for the treatment of human rhinitic diseases. PMID- 1928356 TI - The sugared path to a normal lung: soluble beta-galactoside-specific lectins. AB - The diverse functions of a family of soluble beta-galactoside-binding proteins in lung are discussed. The smallest and most abundant member, a 14-kDa lectin, appears to be a negative modulator of cell growth. Larger members of this family include RL29, a protein involved in the regulation of cytoplasmic RNA levels, and one subunit of the cell surface elastin receptor involved in the regulation of elastic fibrillogenesis. The structure and function of other members of this family remain to be elucidated, but probably homologous carboxy-terminal domains will specify the galactose-binding function and varied amino-terminal domains will specify the diverse biological functions. Although currently these functions are being described at the cellular level, these beta-galactoside-binding proteins appear to have important roles in regulating lung physiology. PMID- 1928357 TI - Serial abnormalities of fibrin turnover in evolving adult respiratory distress syndrome. AB - We studied the changes of coagulation and fibrinolysis in bronchoalveolar lavage (BAL) and plasma obtained serially at intervals after the onset of adult respiratory distress syndrome (ARDS). BAL procoagulant activity was increased at 3 days and tended to decrease thereafter. Tissue factor associated with factor VII was the major BAL procoagulant. Fibrinopeptide A was increased, indicating increased thrombin-mediated conversion of fibrinogen to fibrin. Fibrinolytic activity was usually undetectable in BAL at 3 days post-ARDS and remained depressed for up to 14 days despite unchanged concentrations of urokinase and variably detectable tissue plasminogen activator. Depressed fibrinolytic activity was associated with increased antiplasmin activity and plasminogen activator inhibitor 1 (PAI-1) while PAI-2 concentrations approximated those of control samples and did not change during evolving ARDS. Evidence of systemic coagulopathy and increased systemic fibrin degradation were commonly found in serial ARDS plasma samples, consistent with accelerated vascular and/or extravascular fibrin deposition in these patients. The data indicate that intra alveolar as well as systemic derangements of fibrin turnover are common features of evolving ARDS. Concurrent local abnormalities of both coagulation and fibrinolytic pathways favor persistence of alveolar fibrin for up to 14 days after clinical recognition of ARDS. PMID- 1928358 TI - TGF-beta 1 produces a "prooxidant" effect on bovine pulmonary artery endothelial cells in culture. AB - The pulmonary endothelium is known to be sensitive to oxidant injury, including that of hyperoxia. Similar to effects of exposure to 80-95% O2, porcine platelet transforming growth factor (TGF)-beta 1 at concentrations of greater than or equal to 0.3 ng/ml inhibited proliferation and caused enlargement of bovine pulmonary artery endothelial cells after 24 h of incubation in room air. Uptake of [3H]thymidine, but not of [3H]deoxycytidine, was suppressed by both hyperoxia and TGF-beta 1. The cellular enlargement produced by TGF-beta 1 in room air was attenuated in the presence of anoxia, indicating a need for O2 for TGF-beta 1 to have an effect on cell size. In the presence of 20 microM FeCl3, both TGF-beta 1 and 80% O2 produced marked cellular desquamation from culture dishes. The antioxidants dimethyl sulfoxide and vitamin E partially counteracted the growth inhibitory effect of TGF-beta 1 on endothelial cells. In contrast to its effect on endothelial cells, TGF-beta 1 only moderately altered size and proliferation of smooth muscle cells from the same pulmonary vessels. Uptake of [3H]thymidine by smooth muscle cells was uninfluenced in 48 h by TGF-beta 1, and little, if any, desquamation of these cells occurred with TGF-beta 1 in the presence of 20 microM FeCl3. We propose from these experiments that TGF-beta 1 may produce an oxidant effect on vascular endothelium that is capable of causing injury to this tissue. PMID- 1928359 TI - Sustained production of secretory component by human tracheal epithelial cells in primary culture. AB - Secretory immunoglobulin A (sIgA) is an important initial defense against environmental agents in the airway. The purposes of our study were to determine whether human tracheal epithelial (HTE) cells produce secretory component (SC), the receptor for dimeric IgA (dIgA), to determine whether HTE cells in primary culture continue to produce SC, and if so, to develop a model for studying SC metabolism in the airway. Immunoperoxidase staining of the human trachea using antibody raised against human SC reveals that many surface epithelial cells and the cells of the submucosal glands express SC but basal cells do not. HTE cells, obtained from tracheal specimens at necropsy, contain 10-51 ng of SC/10(5) cells, at the time of isolation. However, when these cells are placed in culture on plastic, SC release diminishes with time (from 19.6 ng/10(5) cells on day 2 to 6.4 on day 8) despite continued cell proliferation. In contrast, HTE cells cultured on floating collagen gels increase SC release over the same period (26.2 ng/10(5) cells on day 2 and 193.9 on day 8). HTE cells cultured on collagen coated and uncoated nitrocellulose filters also produced SC at least through day 8 (collagen coated, 21.5 ng/10(5); uncoated, 6.3). Furthermore, SC was released preferentially to the apical surface (4:1 ratio) under both conditions. This system will allow us to study the production, processing, and release of SC by HTE cells and further understand the transport and function of secretory IgA in the airway. PMID- 1928360 TI - Influence of fetal pulmonary epithelium on thrombin activity. AB - Epithelial injury and intra-alveolar fibrin are present in lung injury. To determine whether healthy fetal and neonatal lung epithelium could regulate thrombin activity (hence fibrin formation) we collected amniotic and postnatal endotracheal tube fluids from humans and directly sampled lung and amniotic fluids from fetal guinea piglets, rabbit pups, and lambs. The coagulant properties of the cell surface and media conditioned by rat fetal type II alveolar epithelium were assessed. All fluids contained glycosaminoglycans (GAGs), but mass and biological assays demonstrated only some (heparan sulfate and to a lesser extent dermatan sulfate) had antithrombin activity. The presence of proteoglycans (greater than 1,000 kDa) yielding active GAGs with less than 100 kDa after base elimination were demonstrated by Sepharose CL4B chromatography. Epithelial-derived fluids contained a factor VII-dependent procoagulant activity, but concentrated conditioned media overlying primary cultures of type II epithelium demonstrated a net antithrombin effect. These studies demonstrate that the lungs of human and nonprimate mammalian fetuses and fetal type II epithelium secrete GAGs, some of which possess antithrombin activity, which would oppose intra-alveolar fibrin formation. PMID- 1928361 TI - Pre- and postjunctional effects of a thromboxane mimetic in canine bronchi. AB - Thromboxane A2 is believed to participate in causation of hyperreactivity of airway smooth muscle (ASM). We therefore investigated the effects of a thromboxane mimetic (U-46619) on isolated ring segments of canine bronchial ASM (3rd to 5th order). U-46619 (10(-9)-10(-5) M) was found to elicit tonic contraction, membrane depolarization, and oscillations in membrane potential. These effects were sensitive to blockade of thromboxane receptors (using 10(-8) M L 670, 596); the mechanical response was insensitive to 3 x 10(-8) M atropine, 10(-7) M nitrendipine, or exposure to Ca(2+)-free media [(containing 0.5 mM ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)]. U 46619 also potentiated electrical field stimulation-elicited contractions and excitatory junction potentials without altering the sensitivity to carbachol. This potentiation was also sensitive to L 670,596 but not to blockade of adrenoceptors (using phentolamine plus propranolol). We conclude that canine bronchial ASM possesses both prejunctional and postjunctional thromboxane receptors. The former potentiate cholinergic neurotransmission through a mechanism not involving adrenoceptors. The latter excite the ASM through a mechanism not involving muscarinic receptors and that utilizes intracellular Ca2+ (rather than extracellular Ca2+). Excitation-contraction coupling was found to be pharmacomechanical in nature (rather than electromechanical). PMID- 1928362 TI - Ozone reduces murine alveolar and peritoneal macrophage phagocytosis: the role of prostanoids. AB - Continuous ozone exposure (0.5 ppm, 1-14 days) reduced the phagocytic activity of murine alveolar and peritoneal macrophages. The response of peritoneal macrophages to ozone was virtually indistinguishable from the response of alveolar macrophages. When added exogenously, prostaglandin E2 (PGE2) inhibited alveolar and peritoneal macrophage phagocytosis. To test the hypothesis that prostanoids mediated the effects of ozone on macrophages, PGE levels of bronchoalveolar lavage fluid (BALF) and the phagocytic activity of macrophages from ozone-exposed mice pretreated with cyclooxygenase inhibitors were measured. PGE levels in BALF were increased following ozone exposure, with high levels of PGE associated with large decreases in phagocytic activity. Pretreatment with indomethacin and d-naproxen completely inhibited ozone-induced increases in PGE recovered by BAL and the suppression of peritoneal macrophage phagocytic activity. The inactive enantiomer of naproxen, l-naproxen, was without effect. Indomethacin partially inhibited ozone-induced suppression of alveolar macrophage phagocytic activity. These observations suggest that prostanoids play a key role in the response to ozone. PMID- 1928363 TI - Fibrinogen degradation product fragment D increases endothelial monolayer permeability. AB - We assessed the effects of the two primary high-molecular-weight fibrinogen degradation products (FDP), fragments D and E, on the pulmonary vascular endothelial barrier function. Fragments D and E were purified to homogeneity by QAE Sephadex chromatography followed by gel filtration. Incubation of bovine pulmonary artery endothelial monolayers with 0.5-2.0 microM fragment D for 2 h caused a doubling of transendothelial 125I-albumin clearance rate (a measure of 125I-albumin permeability). Fragment E only produced a 0.6-fold increase in 125I albumin clearance rate at concentration of 4.0 microM. Both FDP remained active in incubating media with serum. The permeability-increasing effect of fragment D was reversible and was not due to cell detachment or lysis. The fragment-D effect was time dependent and was associated with redistribution of endothelial F-actin microfilaments. The effect was independent of the carboxy-terminal sequence on gamma-chain of fragment D. Fragments D and E binding to pulmonary artery endothelial cells was specific and reversible, but fragment D binding was three fold greater than fragment E, which may account for the greater permeability increase mediated by fragment D. The results indicate that FDP, especially fragment D, increase endothelial permeability to albumin. The response involves specific binding of fragment D to endothelial cells and redistribution of intracellular actin. PMID- 1928364 TI - Potassium dependence of Na-Cl cotransport in dog tracheal epithelium. AB - In confluent primary cultures of dog tracheal epithelium, we tested whether Cl entry across the basolateral membrane is by cotransport with K. Two approaches were taken. First, we measured the inhibition of short-circuit current (Isc) by the K channel inhibitor, Ba2+. Consistent with Na-K-2Cl cotransport, maximal doses of Ba2+ inhibited five-sixths of Isc in tissues previously stimulated to secrete Cl; only two-thirds of Isc should be sensitive to Ba2+ if NaCl cotransport is the entry mechanism. Second, we measured basolateral 86Rb uptake and demonstrated inhibition by bumetanide, an inhibitor of Na-K-2Cl cotransport in other tissues. The degree of inhibition by bumetanide was consistent with the levels of Cl secretion measured as Isc. Uptake of 86Rb was also reduced by removal of Na or Cl, and under these conditions Rb uptake was not further inhibited by bumetanide. These results suggest that the process responsible for Cl entry across the basolateral membrane of tracheal epithelium during Cl secretion is Na-K-2Cl rather than Na-Cl cotransport. PMID- 1928365 TI - DNA distribution analysis of type II pneumocytes by laser flow cytometry: technical considerations. AB - Optimal conditions were established for determination of cell cycle phase fractions of freshly isolated or cultured adult rat type II pneumocytes (T2P). Propidium iodide staining of ethanol-fixed cells treated with ribonuclease (RNase) consistently yielded histograms with low coefficients of variation. Contaminating cells and cell clumps were eliminated during data acquisition through electronic gating based on anti-vimentin immunofluorescence and peak red fluorescence, respectively. Failure to delete contaminants, clumps or RNA resulted in overestimation of S or G2/M phase fractions by as much as 20-fold. When T2P were cultured on plastic at an initial density of 2.5 x 10(5)/cm2, the S phase fraction did not change over a culture interval in which thymidine incorporation rates increased almost 10-fold. In contrast, a significant increase in the G2/M phase fraction by day 2 of culture occurred with no significant increase in cell number. These results support the hypothesis that adult rat T2P, when subjected to customary conditions of primary culture, undergo cell cycle block in G2/M phases. The data also indicate that under these in vitro conditions, net thymidine incorporation by T2P may vary independently of the S phase fraction. The methods described in this report address basic considerations crucial to future applications of flow cytokinetics to the study of T2P proliferation and differentiation. PMID- 1928366 TI - Colchicine has opposite effects on interleukin-1 beta and tumor necrosis factor alpha production. AB - To study the role of microtubules in cytokine production, the effect of the microtubule depolymerizing agent colchicine on lipopolysaccharide endotoxin (LPS) induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) release by blood monocytes and alveolar macrophages were examined. Immunofluorescence microscopy demonstrated that LPS resulted in the appearance of microtubule-containing cytoplasmic appendages and that colchicine, which resulted in microtubule disruption in monocytes, blocked appendage formation. Colchicine resulted in approximately 50% increase in LPS-induced IL-1 beta release and a 50% decrease in LPS-induced TNF-alpha release by human monocytes at all doses of LPS tested. Although colchicine resulted in a statistically significant increase in LPS-stimulated human alveolar macrophage IL-1 beta release, the increase was not as great as that observed with monocytes. Northern blot analysis suggested that the colchicine effect occurs pretranslationally because colchicine caused an increase in LPS-stimulated IL-1 beta mRNA levels and a decrease in TNF-alpha mRNA levels. These results suggest that microtubules contribute to the regulation of endotoxin-stimulated mononuclear phagocyte cytokine production and that this regulation differs significantly between IL-1 beta and TNF-alpha. PMID- 1928367 TI - Ontogenic expression of acetylcholinesterase activity in trachealis of young swine. AB - Previous investigations have demonstrated that cholinergic contraction of porcine tracheal smooth muscle (TSM) decreases between the second and tenth weeks of life. In this investigation, we hypothesized that the greater contractile response to acetylcholine (ACh) in TSM of 2-wk-old swine (2ws) vs. 10-wk-old swine (10ws) was the result of a relative decrease in activity of acetylcholinesterase (AChase). To examine this hypothesis, we assessed AChase activity directly in homogenates of TSM from eight 2ws and seven 10ws using a newly adapted method that measures the rate of cleavage of acetylthiocholine; enzyme activity was expressed as absorbance units per minute per milligram protein. The AChase from tissues of both age groups saturated at approximately 3 mM substrate. However, maximal AChase activity (Vmax) was significantly greater in 10ws than 2ws. Eadie-Hofstee analysis of enzyme kinetics revealed similar Michaelis-Menten constants for 2ws and 10ws. The concentration of physostigmine (PS), an inhibitor of cholinesterase, that elicited half-maximal inhibition of AChase activity also was similar for 2ws and 10ws. In separate studies, contraction of TSM strips was assessed in vitro at optimal resting length and expressed as a function of maximal force generation to potassium chloride. Strips of TSM from 2ws contracted with greater force than those of 10ws. After pretreatment with 10(-8) M PS, contractile forces were similar in 2ws and 10ws. We conclude that AChase activity measured directly in muscle homogenates is significantly reduced in TSM of 2ws vs. 10ws and that this may result in augmented contraction to ACh under conditions of zero-order kinetics. PMID- 1928368 TI - Muscarinic receptor subtypes in guinea pig airways. AB - The muscarinic receptors present in the guinea pig tracheobronchial tree were characterized using ligand-binding studies and functional approaches. The binding constants of four selective antagonists, pirenzepine,[11-([2-[(diethylamino) methyl]-1-piperidinyl]acetyl)-5,11-dihydro-6H-pyrido(2,3) (1,4) benzodiazepine-6 on] (AF-DX 116), methoctramine, and 4-diphenylacetoxy-Nmethylpiperidine methobromide(4-DAMP) were examined. Heterogeneity in the airway muscarinic receptors population was revealed by competitive binding experiments against [N methyl3H]scopolamine with the M2 muscarinic antagonists AF-DX 116 and methoctramine. In guinea pig lung and trachea, AF-DX 116 and methoctramine recognized 86-88% and 50-60% of total receptors with high affinity, respectively. These receptors exhibit binding constants for these two compounds similar to those of the M2 subtype. The low-affinity M2 antagonist binding constants were close to those reported for M3 receptors. In lung and trachea, we found no evidence for a high-affinity [N-methyl-3H]pirenzepine binding sites. In functional studies, pirenzepine, methoctramine, and 4-DAMP inhibited the methacholine-induced contraction of lung parenchymal, main bronchial, and tracheal strips with affinities characteristic of smooth muscle M3 receptors. These results are consistent with the presence of M2 and M3 receptors in guinea pig airways. Throughout the airways, the muscarinic receptors mediating smooth muscle contraction are of the M3 subtype. PMID- 1928369 TI - Alveolar uptake of lipid and protein components of surfactant. AB - We investigated the clearance of radiolabeled natural surfactant from the alveolar space of the isolated perfused rat lung. 3H, 35S-natural surfactant was prepared from rat lungs that had been perfused with [methyl-3H]choline and [35S]methionine. The biosynthesized material contained greater than 95% of 3H in phosphatidylcholine (PC) and approximately 80% of 35S in surfactant protein A. Natural surfactant (1 mumol PC) was instilled into the trachea; lungs were analyzed 5 min later or after 2 h perfusion to determine surfactant uptake, defined as lung lavage-resistant 3H or 35S [% of instilled disintegrations per minute(dpm)]. Uptake at 5 min was 31.4 +/- 0.37% for 3H and 31.9 +/- 0.85% for 35S (mean +/- SE, n = 4). At 2 h, uptake was 46.6 +/- 0.96% for 3H and 45.8 +/- 1.1% for 35S (n = 7). In the presence of 0.1 mM 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), uptake at 2 h for both 3H and 35S was stimulated to approximately 57% of instilled dpm (n = 4). Microsomes and plasma membranes isolated from lung homogenates had a ratio of 3H to 35S that was similar to the original surfactant, whereas 3H/35S in isolated lamellar bodies was increased 2.1 fold. Degradation of lipid was indicated by finding 13.4 +/- 0.65% of homogenate 3H in the aqueous fraction of lung extract after 2 h perfusion; only 2.3 +/- 0.47% of 35S dpm were soluble in trichloroacetic acid, suggesting significantly less protein breakdown. Lipid degradation was increased more than twofold by 8 BrcAMP, whereas protein degradation was not changed significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928371 TI - Direct renal interstitial volume expansion causes exaggerated natriuresis in SHR. AB - In Okamoto spontaneously hypertensive rats (SHR), elevated arterial blood pressure is not transmitted to the renal interstitium, and therefore pressure natriuretic and diuretic responses are attenuated. The objective of this study was to determine the effect of increasing renal interstitial hydrostatic pressure (RIHP) by direct renal interstitial volume expansion (DRIVE) on natriuresis and diuresis of SHR and Wistar-Kyoto rats (WKY). Unilateral nephrectomy and implantation of two polyethylene (PE) matrices were performed 3-4 wk before the acute experiment. Four groups of rats, two experimental and two time control, were used. A control clearance period was taken in all groups. In experimental groups and at the beginning and middle of the second period DRIVE was accomplished by bolus injection of a solution of 2.5% human albumin in saline directly into interstitium through one of the PE matrices. In time-control groups saline was infused in renal interstitium at the beginning of the second period. The second PE matrix was used to continuously measure RIHP in all groups. In experimental groups, DRIVE produced a significant increase in RIHP from 3.8 +/- 0.4 to 5.7 +/- 0.8 mmHg (P less than 0.05) in SHR and 4.3 +/- 0.4 to 7.1 +/- 0.5 mmHg (P less than 0.05) in WKY. In both groups the significant increase in RIHP was associated with significant increases in urinary sodium excretion (UNaV), fractional excretion of sodium (FENa), and urine flow rate (V).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928370 TI - Genetic element from human surfactant protein SP-C gene confers bronchiolar alveolar cell specificity in transgenic mice. AB - Transgenic mice bearing chimeric genes consisting of 5'-sequences derived from the human surfactant protein C (SP-C) gene and the bacterial chloramphenicol acetyltransferase (CAT) gene were generated. Analysis of CAT activity was utilized to demonstrate tissue-specific and developmental expression of chimeric genes containing 3.7 kb of sequences from the human SP-C gene. Lung-specific expression of the 3.7 SP-C-CAT transgene was observed in eight distinct transgenic mouse lines. Expression of the 3.7 SP-C-CAT transgene was first detected in fetal lung on day 11 of gestation and increased dramatically with advancing gestational age, reaching adult levels of activity before birth. In situ hybridization demonstrated that expression of 3.7 SP-C-CAT mRNA was confined to the distal respiratory epithelium. Antisense CAT hybridization was detected in bronchiolar and type II epithelial cells in the adult lung of the 3.7 SP-C-CAT transgenic mice. In situ hybridization of four distinct 3.7 SP-C-CAT transgenic mouse lines demonstrated bronchiolar-alveolar expression of the chimeric CAT gene, although the relative intensity of expression at each site varied within the lines studied. Glucocorticoids increased murine SP-C mRNA in fetal lung organ culture. Likewise, expression of 3.7 SP-C-CAT transgene increased during fetal lung organ or explant culture and was further enhanced by glucocorticoid in vitro. The 5'-regions of human SP-C conferred developmental, lung epithelial, and glucocorticoid-enhanced expression of bacterial CAT in transgenic mice. The increased expression of SP-C accompanying prenatal lung development and exposure to glucocorticoid is mediated, at least in part, at the transcriptional level, being influenced by cis-active elements contained within the 5'-flanking region of the human SP-C gene. PMID- 1928372 TI - High glucose increases diacylglycerol mass and activates protein kinase C in mesangial cell cultures. AB - We showed previously that glomerular mesangial cells displayed increased fibronectin, laminin, and type IV collagen synthesis and mRNA levels when grown in medium containing 30 mM glucose compared with those cells grown in 10 mM glucose [S. H. Ayo, R. A. Radnik, W. F. Glass II, J. A. Garoni, E. R. Rampt, D. R. Appling, and J. I. Kreisberg. Am. J. Physiol. 260 (Renal Fluid Electrolyte Physiol. 29): F185-F191, 1990]. However, total protein synthesis and actin mRNA were unchanged. In this report, we show that an increase in medium glucose concentration resulted in an increase in diacylglycerol (DAG) mass and transiently increased protein kinase C (PKC) activity as assessed by the translocation of PKC from the soluble to the particulate fraction. Effects of increased glucose on DAG were evident at 30 min and were maintained through 1 wk of growth in medium containing 30 mM glucose. Although total PKC activity (i.e., soluble plus particulate fractions) did not change with high-glucose treatment, the percent activity associated with the particulate fraction (i.e., activated PKC) increased significantly after 60 min in RPMI 1640 medium with 30 mM glucose. The distribution of PKC returned to control values by 24 h. High glucose did not stimulate phosphoinositide hydrolysis, as evidenced by the absence of an increase in the water-soluble inositol phosphates, indicating that DAG was not generated through the action of a phosphoinositide-specific phospholipase C. Cells treated with the cell-permeable DAG analogue 1-oleoyl-2-acetyl glycerol to activate PKC displayed approximately two-fold increases of fibronectin, laminin, and type IV collagen mRNA levels after normalization against actin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928373 TI - Glomerular stereospecific synthesis and hemodynamic actions of 8,9 epoxyeicosatrienoic acid in rat kidney. AB - Renal glomerular and cortical metabolism of endogenous arachidonic acid by cytochrome P-450 epoxygenase yields 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EET). Using gas chromatography-mass spectrometry, we measured the synthesis of 8,9-EET from an endogenous pool of arachidonic acid in normal rat kidney. The (8S,9R) isomer was favored over the (8R,9S) isomer in a ratio (%) of 59 to 41 in isolated glomeruli and 68 to 32 in cortex tissue. (8S,9R)- but not (8R,9S)-EET elicited dose-dependent vasoconstriction on intrarenal administration in the euvolemic Munich-Wistar rat. Micropuncture measurements of glomerular dynamics revealed that (8S,9R)-EET increased afferent arteriolar resistance (RA) leading to reductions in single-nephron plasma flow rate (QA), net transcapillary hydraulic pressure difference (delta P), and consequently single-nephron glomerular filtration rate (SNGFR). There was no significant change in the value of the glomerular capillary ultrafiltration coefficient (Kf). In the presence of a cyclooxygenase inhibitor, indomethacin, the effects of 8,9-EET were reversed. RA fell leading to increases in QA and delta P, with resultant augmentation of SNGFR. Under these conditions, a modest reduction if Kf was noted. Thus (8S,9R) EET is a stereoselective renal vasoconstrictor, preferentially generated over its optical isomer, (8R,9S)-EET, suggesting that it is biologically relevant and implying specific structural requirements for EET receptor activation. The principal mechanism of action of 8,9-EET is preglomerular vasoconstriction. The vasoconstrictor effect of 8,9-EET is CO dependent. PMID- 1928374 TI - Effect of protamine on ion conductance of ascending thin limb of Henle's loop from hamsters. AB - To evaluate the contribution of paracellular shunt pathway in ascending thin limb (ATL) of hamsters, we examined the effect of protamine, a selective blocker of paracellular conductance, on salt-diffusion voltage (dVT) and transmural resistance (RT) during in vitro microperfusion. Lumen-negative dVT generated on reduction of lumen NaCl concentration was increased further from -7.3 +/- 0.5 to 10.3 +/- 0.7 mV when 300 micrograms/ml protamine was added to the lumen, and calculated Na+/Cl- permeability ratio was decreased from 0.46 +/- 0.03 to 0.31 +/ 0.03. Although the effect of protamine persisted after removal of the agent from the lumen, addition of 30 U/ml heparin returned the dVT toward the control level. The effect of protamine was dose dependent from 30 to 300 micrograms/ml. Protamine also exerted its effect from the bath, and the effect was inhibited by heparin either from the lumen or from the bath. The inhibitory effect was almost the same when the orientation of imposed NaCl gradient was reversed. Inhibition of transcellular Cl- transport with 0.1 mM 5-nitro-2-(3-phenylpropylamino) benzoate (NPPB) in the bath caused lumen-positive dVT. This voltage was decreased significantly by protamine. Protamine markedly decreased the apparent transference number for Na+ but slightly increased the value for Cl-. Transmural cable analysis showed that 300 micrograms/ml protamine added to the lumen increased RT from 0.59 +/- 0.10 to 1.20 +/- 0.20 omega.cm2, with the effect being reversed by 30 U/ml heparin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928375 TI - IGF-I and its variant, des-(1-3)IGF-I, enhance growth in rats with reduced renal mass. AB - The efficacy of insulin-like growth factor I (IGF-I) in enhancing growth in animals with reduced renal mass was investigated in subtotally nephrectomized young male rats. Recombinant human IGF-I was administered by osmotic minipumps for 7 days at two doses, 0.9 and 2.2 mg.kg body wt-1. day-1, and the truncated analogue of IGF-I, des-(1-3)IGF-I, was given at a dose of 0.9 mg.kg body wt-1.day 1. The partial nephrectomy procedure resulted in significantly impaired renal function as evidenced by elevated serum urea and creatinine concentrations, reduced creatinine clearance, and increased average daily urine output. Carcass composition was significantly altered in animals with reduced renal mass; water content increased and fat content decreased, while protein content remained unchanged. Carcass composition was not affected by IGF treatment. Body weight gain, food utilization, and nitrogen balance during the treatment period were significantly increased in rats treated with IGF-I at both the lower and higher doses and in those treated with des-(1-3)IGF-I. The improved nitrogen balance in the des-(1-3)IGF-I group could at least partly be explained by a diminished rate of muscle protein breakdown, as indicated by the reduced urinary excretion rate of 3-methylhistidine. Compensatory hypertrophy of the remnant kidney was significantly increased in the group treated with the high dose of IGF-I. These results suggest that IGF-I may have beneficial effects on somatic growth and nitrogen balance in renal insufficiency, with des-(1--3)IGF-I being particularly effective in reducing the rate of muscle protein breakdown. PMID- 1928376 TI - Relationship between sodium transport and intracellular ATP in isolated perfused rabbit proximal convoluted tubule. AB - The effect of alterations in sodium transport on cell ATP content and pH in the isolated perfused proximal convoluted tubule (PCT) of the rabbit was examined. Stimulating sodium transport by the addition of luminal glucose and alanine decreased cell ATP from 4.44 +/- 0.93 to 2.69 +/- 0.62 mM (n = 4), increased intracellular pH by 0.13 +/- 0.02 (n = 7), and increased cell volume by 0.10 +/- 0.02 nl/mm (n = 4). Blocking the sodium pump with 10(-4) M strophanthidin in tubules in which sodium transport had been stimulated increased cell ATP from 2.04 +/- 0.24 to 2.42 +/- 0.32 mM (n = 6). In parallel experiments the same dose of strophanthidin depolarized the basolateral membrane from -52.6 +/- 1.9 to -6.4 +/- 1.6 mV, depolarized the transepithelial potential from -3.2 +/- 0.3 to -0.1 +/- 0.1 mV, and reduced the basolateral membrane potassium transference number from 0.47 to 0.26 indicating a reduction in basolateral potassium conductance. Since strophanthidin caused a cell alkalinization of 0.15 +/- 0.03, this latter effect cannot be due to changes of intracellular pH. Strophanthidin caused no change in cell volume over the period studied, suggesting that stretch-activated potassium channels are not involved either. Instead, potassium conductance inhibition may be the result of the closure of ATP-sensitive potassium channels. These same channels might thus be partly responsible for the increase in potassium conductance commonly observed during stimulation of sodium transport. PMID- 1928377 TI - Phosphate transport in kidneys: effect of transmembrane electrical potential. AB - The effect of a transmembrane electrical potential on phosphate transport by kidney brush-border membrane vesicles was studied. The initial rate of Na(+) dependent phosphate influx was twice as high as that of efflux. Generation of a negative transmembrane potential had a stimulatory effect on the rate of influx but had no effect on efflux. The Na+ saturation curve for phosphate influx was sigmoidal, and the Hill coefficients were similar, in the presence and absence of a transmembrane potential. The membrane potential increased both the affinity for phosphate and the maximal velocity (Vmax) of the transporter. In the absence of a Na+ gradient, the stimulation by the potential was 1.78-fold. When a proton gradient (in greater than out) was the driving force, the electrical potential stimulated phosphate transport 1.71-fold. Internal Na+ (trans) inhibited phosphate influx whether a potential was present or not. Internal phosphate (trans) stimulated phosphate influx in the absence of a potential but not in its presence. These results indicate that the electrical potential is an important driving force for the Na(+)-phosphate carrier and that the translocation of the carrier is a potential-dependent step. PMID- 1928378 TI - Multiple carriers for dipeptide transport: carrier-mediated transport of glycyl-L proline in renal BBMV. AB - To determine whether multiple carriers are responsible for luminal uptake of glycyl-L-proline (Gly-Pro) in the renal proximal tubule, transport of Gly-[3H]Pro was measured in brush-border membrane vesicles (BBMV). A Line-weaver-Burk analysis of Michaelis-Menten kinetics revealed the presence of two carriers: a lower affinity, higher capacity carrier (Km = 1.3 x 10(-2) M; Vmax = 4.6 x 10(-8) mol.mg-1.min-1) and a higher affinity, lower capacity carrier (Km = 2.7 x 10(-7) M; Vmax = 7.8 x 10(-13) mol.mg-1.min-1). The dipeptides Gly-Sar, beta Ala-His, and pyroGlu-His competitively inhibited the low-affinity carrier. No effect on the Km or Vmax of Gly-Pro transport in this range was seen in the presence of the dipeptides Gly-Gly or cycloHis-Pro. The high-affinity carrier exhibited a different inhibition spectrum. Competitive inhibition of Gly-Pro transport was demonstrated for the dipeptides Gly-Gly and Gly-Sar. However, none of the other peptides tested above altered Gly-Pro transport in the high-affinity range, including pyroGlu-His, which is transported by a high-affinity carrier. At both low (4 x 10(-8) M) and high (4 x 10(-3) M) concentrations, uptake of Gly-Pro was stimulated in the presence of an inwardly directed H+ gradient but was unaffected by the presence of an inward Na+ gradient. In addition, measurements in the presence of valinomycin and an outwardly directed K+ gradient strongly suggest that H(+)-stimulated uptake at both concentrations is electrogenic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928379 TI - Biochemical and immunological characterization of renal protein kinase C. AB - Protein kinase C (PKC) plays an important role in regulation of renal transport and metabolic function. To understand the role of a specific PKC isozyme in renal homeostasis, alpha-PKC content, regulation, and localization have been characterized. Immunoadsorption assays were used to determine that 34% of the total rat kidney PKC (measured as phorbol ester receptors) was alpha-PKC. Immunohistochemical staining with alpha-PKC-specific monoclonal antibodies determined that alpha-PKC was present throughout the nephron and was especially concentrated in proximal tubules and papillary collecting ducts. In general, the S3 segment of the proximal tubule stained more intensely than the S1-S2 segments. Cortical collecting ducts stained poorly for alpha-PKC. Interstitial cells of the papilla also stained for alpha-PKC. Subcellular distribution of alpha-PKC could not be determined in tissue sections; however, in cultured proximal tubule epithelial cells, alpha-PKC was localized not only in cytoplasm but also in cell cell borders and focal contacts. Chromatography of rat kidney soluble fraction revealed two endogenous kinase inhibitors, one which is PKC specific and one which is a more general kinase inhibitor. The presence of negative regulators of PKC activity suggests that both activation and inactivation of PKC are important for normal renal function. PMID- 1928380 TI - Adult and fetal human mesangial cells interact with specific laminin domains. AB - Mesangial cells are centrally located pericytes in the renal glomerulus. They are surrounded by an extracellular matrix and directly contact the glomerular basement membrane in vivo. Because these interactions are critical for renal development and function, we have studied human mesangial cell interactions with laminin, a major adhesive component of basement membranes present in the extracellular matrix of the mesangium. Human fetal and adult mesangial cell attachment was stimulated by both laminin and the laminin-derived synthetic peptides YIGSR-NH2, CQAGTFALRGDNPQG-NH2, and CIKVAVS-NH2. Furthermore, mesangial cells spread on laminin as well as on both the RGD-containing and CIKVAVS peptides. When added in solution, all three peptides inhibited mesangial cell attachment to laminin, and the latter two peptides inhibited mesangial cell spreading on laminin. Laminin affinity column chromatography demonstrated several low-molecular-mass laminin-binding proteins ranging from between 35 and 42 kDa, which predominated in fetal mesangial cells, whereas a higher molecular mass laminin-binding protein of 65 kDa was predominant in adult mesangial cells. Western blot analysis with an anti-32-kDa laminin-binding protein antibody showed increased expression of both 31- and 42-kDa proteins in fetal mesangial cells when compared with the adult. The antisera to the 32-kDa laminin-binding protein also inhibited fetal mesangial spreading on the CIKVAVS peptide. Western blot analysis with an anti-67-kDa laminin-binding protein antibody revealed a 110-kDa protein in adult mesangial cells that was not present in fetal mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928381 TI - Apical maxi K channels in intercalated cells of CCT. AB - High-conductance (maxi) K channels in the apical membrane of rat and rabbit cortical collecting tubules (CCT) were studied using the patch-clamp technique. Principal cells (PC) and intercalated cells (IC) were distinguished with Hoffman modulation optics in split-open tubules. IC were further identified by staining tubules with the fluorescent mitochondrial dye, rhodamine 123. Maxi-K channels were distinguished by their high conductance (greater than 80 pS) and voltage dependent kinetics. In CCT of rats on a low-Na diet, maxi K channels were observed in 11% of the cell-attached patches on PC and 79% of patches on IC. In rats on a normal diet, the channels were seen in 23 and 79% of patches on PC and IC, respectively. In the rabbit CCT, maxi K channels were observed in 12% (4 of 32) of the patches on PC and 82% (122 of 148) of the patches on IC. The greater abundance of channels in IC was confirmed in rat CCT using the whole-cell clamp technique. Current through the maxi K channels (IK) was measured as the tetraethylammonium (TEA)-sensitive (2.5 mM) outward current in cells equilibrated with 115 mM K and 10(-5) M Ca2+ in the pipette solution. When the cell was clamped to an internal potential of +40 mV, the average IK per cell was -4 +/- 5 pA in PC and 290 +/- 90 pA in IC. Lowering cytoplasmic Ca2+ from 10(-5) M to 10( 7) M reduced IK to 32 +/- 21 pA. Neither single Na channels nor amiloride sensitive whole-cell currents were seen in IC. Finally, maxi K channels could be activated by pipette suction (10-40 cm H2O) in either cell-attached or inside-out patches on IC from rabbit CCT. This mechanosensitivity was observed even after chelation of free Ca2+ with ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N' tetraacetic acid (EGTA) in the pipette or the bath solutions, implying that stretch activation of these channels was not mediated by increased Ca2+ entry into the cell. The IC maxi K channel may play a role in cell volume regulation or in K secretion during elevation of luminal hydrostatic pressure. PMID- 1928382 TI - PAH extraction and estimation of plasma flow in diseased human kidneys. AB - We have analyzed the efficiency with which p-amino-hippuric acid (PAH) is extracted (EPAH) by patients with healthy kidneys (n = 13) or kidneys damaged by chronic cyclosporin nephropathy (n = 21) or primary glomerulopathy (n = 12); respective values (mean +/- SE) for EPAH were 0.87 +/- 0.03, 0.77 +/- 0.03, and 0.69 +/- 0.04. Judged by a 131I-hippuran-to-PAH clearance ratio of 0.75 +/- 0.05, extraction ratio of hippuran was less efficient than EPAH in three glomerulopathic patients. A direct relationship was defined between EPAH and glomerular filtration rate (GFR) (r = 0.54) or calculated efferent oncotic pressure (IIE; r = 0.41, P less than 0.01). Curve fitting by means of quadratic spline functions revealed GFR and IIE to be additive in predicting EPAH (R2 = 0.45). Linear model prediction methods and a sample reuse technique failed to predict EPAH reliably from GFR and preglomerular oncotic pressure (IIA); however, 95% prediction intervals exceed 0.30 EPAH units in width. We conclude that oncotic pressure (presumably reflecting albumin concentration) along with GFR is predictive of EPAH depression in humans with chronic renal disease. However, even sophisticated curve-fitting techniques are too imprecise for accurate prediction of EPAH in a given individual. We submit that renal venous sampling to determine EPAH continues to be necessary for the accurate determination of the rate of plasma flow in the injured human kidney. PMID- 1928383 TI - Identification of C-type natriuretic peptide in heart of spiny dogfish shark (Squalus acanthias). AB - An unidentified atrial natriuretic peptide (ANP)-like substance is the principal hormone regulating NaCl secretion in the shark rectal gland, an epithelial model tissue for hormone-sensitive secondary active chloride transport. Antibodies to mammalian ANP do not recognize the prohormone of marine species. The polymerase chain reaction (PCR) was used to isolate a partial cDNA encoding the shark heart natriuretic peptide. Using this partial sequence as a probe, the full-length clone [882 base pairs (bp)] was obtained from a shark heart cDNA library. Amino acids 119-135 are similar to the recently identified peptide sequences of porcine C-type natriuretic peptide (CNP) and killifish brain natriuretic peptide isolated from the brain of these species. Mature shark heart CNP terminates at the second cysteine residue and lacks a COOH-terminal extension, in contrast to cardiac ANP like peptides of all other species. The primary amino acid sequence of the shark heart prepro-CNP is distinctly different from all other cardiac natriuretic peptides. Amplification of genomic DNA spanning the coding region produced a 1.5 kb product, indicating the presence of at least one intron. Sequencing confirmed the presence of two exons of 90 and 315 bp, separated by a 1.1-kb intron. This is the first report of a cDNA encoding in nonneuronal tissue. Elasmobranch CNP may represent a primordial form of ANP-like peptides that evolved as an adaptation to environmental osmoregulatory stress. PMID- 1928384 TI - Positive inotropism in hypothermia partially depends on an increase in maximal Ca(2+)-activated force. AB - We investigated the contribution of maximal Ca(2+)-activated force to the positive inotropism induced by mild hypothermia. Phosphorus-31 nuclear magnetic resonance spectroscopy revealed that neither energy-related phosphorus compounds in myocardium nor intracellular pH was responsible for the change in contractility. Maximal Ca(2+)-activated pressure (MCAP), the intact-heart correlate of maximal Ca(2+)-activated force, was determined in isolated perfused rabbit hearts by measuring isovolumic left ventricular pressure during tetani at extracellular Ca2+ concentrations greater than or equal to 10 mM. Tetani were elicited by rapid pacing after exposure to ryanodine. MCAP increased by 2.17 +/- 0.28% (mean +/- SE, P less than 0.001, n = 19) for each degree of myocardial cooling between 30 and 38 degrees C. Our results indicate that a primary change in myofilament Ca2+ responsiveness underlies the positive inotropism in hypothermia. The increase in maximal Ca(2+)-activated force may explain the observation of positive inotropism without an upward shift in the relation between oxygen consumption and pressure-volume area, as previously reported for cooled whole hearts. PMID- 1928385 TI - LV-arterial coupling: interactive model to predict effect of wave reflections on LV energetics. AB - The interaction between the left ventricle (LV) and the arterial system was simulated using sequential convolution of the flow output generated by a time varying elastance model of the LV with an impulse response calculated from a 128 element model of the arterial system. The model illustrates the effect of independent changes of components of the arterial load on LV performance and energetics. This report studies the response of the model LV to an increase in arterial resistance, a decrease in arterial compliance, and an increase in discrete vascular reflections. Although arterial resistance exerts the greatest effect on ventricular stroke output, a reduction of arterial compliance or an increase in early reflections resulted in less optimal coupling of the heart to the arteries and less efficient energy utilization by the LV. In addition, the earlier the reflections return, the greater the disturbance of ventricular arterial coupling. PMID- 1928386 TI - Hyperpolarization contributes to endothelium-dependent relaxations to acetylcholine in femoral veins of rats. AB - The contribution of membrane hyperpolarization to endothelium-dependent relaxations induced by acetylcholine was investigated in the femoral vein of the rat using a microelectrode technique and isometric tension recordings. Acetylcholine caused endothelium-dependent relaxations and hyperpolarization in tissues contracted with norepinephrine. The relaxation was sustained during a prolonged exposure to acetylcholine (less than or equal to 10 min). In contrast, the hyperpolarization declined with time. In the presence of nitro-L-arginine, a blocker of nitric oxide synthesis, the relaxation became smaller and transient, whereas the hyperpolarization was not affected. There was a temporal relationship between the relaxation and the hyperpolarization in the presence of nitro-L arginine, when the two parameters were recorded simultaneously. In tissues contracted with 60 mM K+, in which hyperpolarization could not be observed, acetylcholine caused relaxations and these relaxations were abolished by nitro-L arginine. The results suggest a contribution of both nitric oxide and membrane hyperpolarization to the endothelium-dependent relaxation induced by acetylcholine in the femoral vein of the rat. PMID- 1928387 TI - Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation. AB - This study examined the hypothesis that formation of endothelium-derived relaxing factor (EDRF) in the brain has a greater influence on basal tone in large arteries than arterioles. Diameters of the basilar artery and its branches and of arterioles on the cerebrum were measured through cranial windows in anesthetized rats. Under control conditions, topical application of NG-monomethyl-L-arginine (L-NMMA), which inhibits formation of EDRF or nitric oxide (NO) from L-arginine, produced concentration-related constriction that was dependent on initial vessel diameter. Large arteries [diameter = 275 +/- 10 microns (mean +/- SE)] constricted by 10.4 +/- 0.8% in response to 10(-5) M L-NMMA. In contrast, arterioles (62 +/- 6 microns) constricted by only 3.7 +/- 0.6% (P less than 0.01 vs. large arteries), regardless of brain region. U-46619 produced similar constriction of large arteries and arterioles, which indicates that reduced responses to L-NMMA in arterioles is not due to impaired constrictor capacity. Sodium nitroprusside produced similar dilatation of large arteries and arterioles, which suggests that activity of guanylate cyclase is not reduced in small vessels. Dilator responses of large arteries and arterioles to acetylcholine, but not nitroprusside, were inhibited by L-NMMA. Thus synthesis of EDRF from L-arginine influences basal tone of cerebral blood vessels, and the effect is greatest in large arteries. In contrast, the role of EDRF or NO in mediating responses to acetylcholine in the cerebral circulation is similar in large arteries and the microcirculation. PMID- 1928388 TI - Effects of free fatty acids and dichloroacetate on isolated working diabetic rat heart. AB - It is well established that cardiac dysfunction independent of atherosclerosis develops in both humans and animals with diabetes mellitus. The etiology is complex, involving many different processes, one of which may be increased fatty acid utilization and/or a concomitant decrease in glucose utilization by the diabetic heart. We compared control and 6-wk streptozotocin (STZ)-induced diabetic isolated working rat hearts and were able to demonstrate cardiac dysfunction in the diabetic as assessed by depressed heart rate (HR), heart rate peak systolic pressure product (HR.PSP), left ventricular developed pressure (LVDP), and rate of pressure rise (+dP/dt). Paralleling depressed cardiac function in the diabetic were hyperglycemia, hyperlipidemia, and decreased body weight gain compared with age-matched controls. The addition of free fatty acids, in the form of 1.2 mM palmitate, to the isolated working heart perfusate had no effect on either control or diabetic heart function, with the exception of a depressive effect on +dP/dt of diabetic hearts. But diabetic hearts perfused with palmitate-containing perfusate plus the glucose oxidation stimulator dichloroacetate (DCA) showed a marked improvement in function. HR and HR.PSP in spontaneously beating hearts, as well as LVDP and +dP/dt in paced hearts were all restored to control heart values in diabetic hearts perfused in the presence of DCA. Creatine phosphate and ATP levels were similar under all perfusion conditions, thus eliminating energy stores as the limiting factor in heart function. Results indicate that DCA will acutely reverse diabetic cardiac function depression. Therefore glucose oxidation depression in the diabetic heart may be a significant factor contributing to cardiac dysfunction. PMID- 1928389 TI - Slope of human left ventricular end-systolic force-length relation is independent of myocardial length. AB - We have introduced a new contractility index (Ec), i.e., the slope of the left ventricular (LV) end-systolic force-length (Fes-Les) relation. To examine whether Ec was dependent on the LV wall myocardial length, 16 normal hearts of human subjects were evaluated to determine the LV end-systolic force-dimension (Fes Des) and pressure-dimension (Pes-Des) relations (dimension denotes the distance between the LV septum and posterior wall). LV end-systolic pressures and dimensions were estimated simultaneously by intra-arterial cannulation and LV echocardiography. In seven subjects, the effect of a dobutamine infusion was also assessed. The Fes-Des relation was found to be nearly linear. Slopes and extrapolated dimension intercepts were obtained for the LV Fes-Des and Pes-Des relations [Ec, slope of LV Pes-Des relation (Es), and extrapolated dimension intercept of LV Fes-Des (Do), and of Pes-Des relation (D'o), respectively]. Es showed a hyperbolic relation to the baseline LV Des, whereas Ec was unrelated to it. The average variation for Ec (9.5%) was smaller than that for Es (22.5%). Dobutamine infusion increased Ec, Es, and D'o, whereas Do was not changed. Thus the assumption of linearity of the LV Fes-Les relation was found to be reasonable in normal human hearts. Do appears to provide a more accurate parameter than D'o for estimating the actual unstressed myocardial length, whereas Ec could possibly serve as an index of LV wall performance in the normal human heart that is independent of myocardial length and nearly constant between individuals. PMID- 1928390 TI - Superoxide dismutase recovers altered endothelium-dependent relaxation in diabetic rat aorta. AB - Experiments were designed to characterize endothelium-dependent relaxation in thoracic aortic rings obtained from streptozotocin-induced diabetic rats. When the degree of the peak relaxation was compared, the endothelium-dependent relaxant responses to acetylcholine, histamine, or ADP in precontracted aortic rings showed that there was no significant difference between diabetic and control vessels. However, the time courses appeared quite different. The endothelium-dependent relaxant responses in diabetic vessels were more transient than those in control vessels. In addition, the rapid fade of the endothelium dependent responses observed in diabetic vessels was significantly suppressed by pretreatment with superoxide dismutase. Pretreatment with catalase, deferoxamine, allopurinol, or indomethacin did not prevent the rapid fade of the endothelium dependent relaxation. The endothelium-independent relaxation induced by nitric oxide also faded more quickly in diabetic vessels; this impairment was less pronounced in the presence of superoxide dismutase. These results suggest that the transient nature of the endothelium-dependent relaxation is more marked in diabetic rat aorta as a result of an enhanced accumulation of superoxide anion. PMID- 1928391 TI - Tone, autoregulatory properties, and wall thickness-to-radius ratio in skeletal muscle arterioles. AB - Internal diameter, wall thickness, wall thickness-to-radius ratio (W/r), and blood flow velocity in arterioles of different branching orders were measured in the rat cremaster muscle. The heterogeneity of W/r increased in more distal orders. During papaverine treatment, there was a direct correlation between vasodilation and W/r. When pressure was decreased by 20%, 42% of arterioles showed autoregulation; the remaining arterioles constricted in proportion to initial W/r. Similarly, the dilatation of arterioles with autoregulatory properties increased with initial W/r. It is concluded that W/r is an important parameter quantitatively related to tone, mechanical characteristics, and autoregulatory properties of arterioles. PMID- 1928392 TI - Cerebral oxidative metabolism and redox state during hypoxia-ischemia and early recovery in immature rats. AB - Intracellular pH (pHi) and cytoplasmic and mitochondrial oxidation-reduction (redox) states of cerebral tissue were examined in relation to perturbations of glycolytic and tricarboxylic acid cycle intermediates and of high-energy phosphate reserves during hypoxia-ischemia and the early recovery period in the immature rat. Seven-day postnatal rats underwent unilateral common carotid artery ligation and exposure to 8% O2 for 3 h, after which they were quick frozen in liquid N2 at the terminus of hypoxia-ischemia and at 10, 30, 60, and 240 min of recovery for enzymatic fluorometric analysis of cerebral metabolites. During hypoxia-ischemia, concentrations of glucose and alpha-ketoglutarate in the cerebral hemisphere ipsilateral to the carotid artery occlusion were depleted to 10 and 70% of control, respectively; pyruvate was unchanged. During recovery, glucose, pyruvate, and alpha-ketoglutarate increased above their respective control values. Calculated pHi decreased from 7.0 (control) to 6.6 during hypoxia ischemia and normalized by 10 min of recovery. The cytoplasmic NAD+/NADH ratio decreased (increased reduction) to 50% of control during hypoxia-ischemia and remained in the reduced state throughout 4 h of recovery. Paradoxically, mitochondrial NAD+/NADH was oxidized at the terminus of hypoxia-ischemia. The mitochondrial oxidation which developed during hypoxia-ischemia presumably results from a limitation of cellular substrate (glucose) supply, which in turn leads to a depletion of high-energy phosphate reserves, culminating in brain damage. PMID- 1928393 TI - Reperfusion-induced contracture develops with a decreasing [Ca2+]i in single heart cells. AB - The causal relationship between intracellular Ca2+ overloading and reperfusion induced contracture was examined from changes in intracellular Ca2+ concentration ([Ca2+]i) at rest, changes in the magnitude and time course of intracellular Ca2+ transients, and the development of contracture. Single myocytes isolated from guinea pig hearts were subjected to the conditions mimicking ischemia and reperfusion. Ischemic condition was produced by superfusing myocytes with hypoxic substrate-free solutions containing elevated concentrations of K+, H+, and lactate as described by Ferrier et al. (Circ. Res. 56: 184-194, 1985). Changes in [Ca2+]i were estimated using fura-2 as the Ca2+ indicator. Under these conditions, twitch contractions were suppressed during simulated ischemia associated with an early and gradual rise of [Ca2+]i. The development of contracture, however, was not observed. Upon "reperfusion" of myocytes that had been subjected to 20 min of the above "ischemic" condition, the elevated [Ca2+]i declined rapidly. With the recovery of twitch contractions, contracture developed despite a substantial decrease in [Ca2+]i. These results indicate that reperfusion-induced contracture is not associated with a concomitant increase in [Ca2+]i in isolated myocytes. PMID- 1928394 TI - Measurement of mitochondrial free Ca2+ concentration in living single rat cardiac myocytes. AB - A technique that allows the continuous measurement of mitochondrial free Ca2+ ([Ca2+]m) in a single living cardiac myocyte is described. It involves the introduction of the fluorescent chelating agent indo-1 into the cell by exposure to the acetoxymethyl ester, followed by selective quenching of the fluorescence of indo-1 in the cytosol by Mn2+. The identity of the remaining fluorescence due to intramitochondrial indo-1 is established by its resistance to treatment of the cell with digitonin at concentrations that release cytosolic but not mitochondrial enzymes and by the finding that ruthenium red and carbonyl cyanide p-trifluoromethoxyphenylhydrazone prevent its response to elevated cytosolic free Ca2+ ([Ca2+]c). [Ca2+]m is found to be low (less than 100 nM) in unstimulated cells and to rise in procedures that chronically elevate [Ca2+]c, such as Na+ replacement. The gradient [Ca2+]m/[Ca2+]c is less than unity at values of [Ca2+]c of less than 500 nM but rapidly increases at higher values of [Ca2+]c. Although there is no detectable increase in [Ca2+]m during a single electrical stimulation, [Ca2+]m increases up to 600 nM as the pacing frequency is raised to 4 Hz in the presence of norepinephrine; this increase occurs over the course of many contractions. It is concluded that these findings are consistent with an increase in [Ca2+]m acting as a signal to increase dehydrogenase activity, and hence flux through oxidative phosphorylation, in response to increased work loads. PMID- 1928395 TI - Association of pulmonary artery photorelaxation with H2O2 metabolism by catalase. AB - We have examined the mechanism governing guanosine 3',5'-cyclic monophosphate (cGMP)-associated photoinduced relaxation elicited by long-wavelength ultraviolet (UV) light of endothelium-removed, isolated bovine pulmonary arteries. Hypoxia, produced by gassing of the organ bath solution with 95% N2-5% CO2, inhibited photorelaxation. Photorelaxation was also inhibited by cyanide (1 mM NaCN) but was potentiated by lactate (5 mM). Irradiation of bovine pulmonary arterial smooth muscle with UV light (or exposure to exogenous H2O2) stimulated cyanide inhibitable oxidation of methanol to formaldehyde, suggesting that UV light increased H2O2 metabolism via catalase. The UV light-induced oxidation of methanol by pulmonary arterial smooth muscle was also inhibited by hypoxia. Consumption of O2 was detected when pulmonary arterial tissue was exposed to UV light, but cyanide failed to interfere with this effect, consistent with the photochemical reduction of O2 within vascular smooth muscle in a manner independent of mitochondrial respiration. We propose that photorelaxation is associated with the intracellular photochemical reduction of O2 to form H2O2, which elicits increases of vascular smooth muscle cGMP levels via the catalase dependent activation of soluble guanylate cyclase. In addition, we hypothesize that the photooxidation of NAD(P)H could contribute to the generation of H2O2, since the enhancement of photorelaxation by lactate may originate from increased levels of NADH. PMID- 1928396 TI - Circulatory changes following premature delivery in a baboon model of hyaline membrane disease. AB - The premature baboon delivered by hysterotomy at 140 +/- 2 days (75%) gestation develops hyaline membrane disease (HMD) and left-to-right (L-R) shunting through the patent ductus arteriosus (PDA). To characterize hemodynamic changes that follow premature delivery, we measured systemic and organ blood flow, oxygen transport, and systemic vascular resistance over the first 96 h of life. We compared these measurements with those from more mature animals of the same species. Radiolabeled microspheres were used to measure organ blood flow (in ml.min-1.g-1) at 3 (n = 18), 23 (n = 17), and 96 h (n = 4) in the premature animals, and at 13 +/- 4 mo in the older animals (n = 5). Premature animals demonstrated over the first 96 h of life significant hemodynamic changes that included decreased systemic vascular resistance (P less than 0.001), increased systemic (P less than 0.05), intestinal (P less than 0.05), and hepatic blood flow (P less than 0.05), as well as resolution of L-R PDA shunting. These 96-h values were similar to those of the more mature infant baboons. Blood flow and oxygen transport to the kidneys and cerebrum did not significantly increase over the first 96 h in premature baboons and were significantly less than those of 13 mo-old animals (P less than 0.01, both). We speculate that low renal and cerebral blood flow in the 140-day premature baboon are manifestations of multisystem immaturity and, as such, may represent persistent physiological disturbances that are distinct from the severity of underlying lung disease in HMD. PMID- 1928397 TI - 31P-NMR studies of isolated adult heart cells: effect of myoglobin inactivation. AB - 31P nuclear magnetic resonance (NMR) studies of isolated adult rat heart cells revealed that the cells maintained high-energy phosphates for up to 6 h in polyamide hollow fibers perfused with well-oxygenated nutrient medium. Glucose plus pyruvate superfused heart cells maintained [phosphocreatine]/[ATP] at 1.4 +/ 0.1, internal pH at 7.09 +/- 0.04 (external pH = 7.25), and intracellular free Mg2+ at 0.51 +/- 0.04 mM. In glucose-containing media, hypoxia was accompanied by a reversible decrease in intracellular ATP and phosphocreatine of approximately 50% and 80%, respectively, while the intracellular free Mg2+ was reversibly increased by 40%. However, inhibition of glycolysis by iodoacetate in aerobic pyruvate-containing medium did not significantly alter high-energy phosphate content. Inactivation of intracellular myoglobin with 1-2 mM sodium nitrite, which reduces the steady-state respiratory oxygen consumption rate by 30%, caused a significant (30%) decrease in intracellular phosphocreatine peak, which was reversed upon removal of sodium nitrite. The nitrite-induced decrease in phosphocreatine was also observed in iodoacetate-treated myocytes but not in oligomycin-treated cells. These results indicate that functional myoglobin enhances high-energy phosphate synthesis in well-oxygenated myocytes. PMID- 1928398 TI - Cardiac contractile injury after intestinal ischemia-reperfusion. AB - Experimental and clinical data suggest that even a brief period of intestinal ischemia followed by reperfusion initiates a sequence of events that include release of inflammatory mediators and multiorgan failure. In this study, 41 rats were subjected to occlusion of the superior mesenteric artery (SMA) for 20 min and collateral arcade ligation. Twelve rats were sham operated and served as controls (group 1). Groups of rats with SMA occlusion were killed at several time intervals after reperfusion (group 2, 2-3 h; group 3, 4-5 h; group 4, 12-16 h). In group 5, rats were pretreated with enterally administered allopurinol (10 mg.kg-1.day-1) for 4 days before the intestinal ischemia episode and were studied 2-3 h after reperfusion. In vivo studies confirmed that 20 min of intestinal ischemia produced a transient bradycardia (P less than 0.05) and no change in systemic blood pressure, acid-base balance, or hematocrit. In vitro studies showed marked cardiac contractile depression as early as 2 h after ischemia reperfusion as indicated by a fall in left ventricular pressure (LVP; from 77 +/- 3 to 63 +/- 4 mmHg, P = 0.01) and +dP/dtmax (from 1,827 +/- 59 to 1,557 +/- 99 mmHg/s, P less than 0.02) and -dP/dtmax (from 1,267 +/- 57 to 953 +/- 67 mmHg/s, P = 0.02), a rightward shift in LV function curves, and a decreased responsiveness to perfusate Ca2+. Allopurinol pretreatment prevented ischemia reperfusion-mediated deficits in cardiac contraction and relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928399 TI - Morphological and functional alterations of mesenteric small resistance arteries in early renal hypertension in rats. AB - We investigated the structure and reactivity of small resistance arteries of two kidney, one-clip (2K,1C) and one-kidney, one-clip (1K,1C) Goldblatt hypertensive rats within 4-6 wk of development of hypertension. Blood vessels from the mesenteric vascular bed with lumen diameter less than 300 microns were mounted on a wire myograph. The media of the vessel wall was significantly increased and lumen diameter was decreased in 2K,1C and 1K,1C rats. External diameter of blood vessels was reduced in both 2K,1C and 1K,1C rats, whereas cross-sectional area of the wall was increased significantly in 1K,1C rats. Wall tension in response to KCl was significantly lower in 2K,1C and 1K,1C hypertensive rats, whereas tension in response to norepinephrine (NE) was reduced in 1K,1C hypertensive rats but was similar in 2K,1C rats and controls. Active tension in response to arginine vasopressin (AVP) was similar in all groups. As a consequence of the reduced lumen circumference of small arteries, effective pressure in response to NE was similar in hypertensive and control rats, whereas effective pressure in response to AVP was exaggerated in the hypertensive rats. The sensitivity to NE and AVP was similar in all groups. These results show the rapid development of functional and structural changes in small resistance arteries in renal hypertensive rats within 4-6 wk of hypertension, with significant reduction in external and lumen diameters, increased media width, and increased media-to-lumen ratio, which enhance vascular reactivity to vasoconstrictors, in particular NE and AVP. PMID- 1928400 TI - Effect of in vivo inhibition of neutrophil adherence on skeletal muscle function during ischemia in ferrets. AB - Neutrophils are reported to play an important role in the genesis of tissue damage during reperfusion after periods of ischemia in a variety of organs and may also be involved in loss of tissue function during ischemia. To test this hypothesis, the monoclonal antibody, MoAb 60.3, which prevents the adhesion of ferret neutrophils to cultured human endothelial cells at a concentration of 30 micrograms/ml, was tested in a model of peripheral vascular disease to determine whether it would preserve skeletal muscle function during ischemia. In an anesthetized ferret the muscles of the hindlimb were stimulated electrically to contract isometrically and the force of contraction was measured. Under normal perfusion conditions the contractile force peaked within 1 or 2 min of initiation of stimulation and gradually declined to approximately 80% of peak force after 20 min. When femoral arterial pressure was reduced to 45 mmHg by partial occlusion of the abdominal aorta, peak force was reduced by 25 +/- 7%, and within 5 min the force decayed to approximately 20% of the original peak, resulting in an area under the force-time curve (AUC) of 32 +/- 5% of that seen during the normal flow period. During ischemia after treatment with MoAb 60.3 (2 mg/kg iv), peak force was 94 +/- 3% and AUC was 49 +/- 5% of that observed during the normal flow period, a significant protective effect compared with the untreated control group (P = 0.0294). When the nonneutrophil-directed monoclonal antibody, L6, was tested in this model, no protective effects were evident.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928401 TI - Competition between cutaneous active vasoconstriction and active vasodilation during exercise in humans. AB - Cutaneous vasoconstriction occurs in response to the initiation of dynamic exercise in hyperthermia. To find whether this response was due to increased vasoconstrictor activity or to withdrawal of active vasodilator activity, blood flow monitoring with laser-Doppler flowmetry (LDF) was combined with the local iontophoresis of bretylium. Each of six male subjects had two forearm sites treated with bretylium for selective local blockade of noradrenergic vasoconstrictor nerves in skin. LDF was monitored at those sites and at two adjacent untreated sites. Mean arterial pressure (MAP) was measured, and cutaneous vascular conductance (CVC) was calculated as LDF/MAP. After iontophoresis, subjects underwent 3 min of cold stress (water-perfused suits) to verify vasoconstrictor blockade. CVC at untreated sites fell by 35.9 +/- 3.1% (P less than 0.01) and at bretylium-treated sites was not significantly changed (P greater than 0.10). During strenuous exercise in normothermia, CVC at untreated sites fell by 16.1 +/- 4.1% (P less than 0.05) and was unchanged at bretylium treated sites (+12.7 +/- 6.6%, P greater than 0.05). Whole body heat stress was then applied. When exercise was repeated in hyperthermia, CVC at untreated sites fell by 11.6 +/- 3.8% (P less than 0.05) but was not significantly changed at bretylium-treated sites (+3.6 +/- 3.0%, P greater than 0.30). Following return to normothermia, cold stress verified the persistence of the blockade. We conclude that exercise initiation causes a cutaneous vasoconstriction largely or entirely due to enhanced active vasoconstrictor tone in both normothermia and hyperthermia. Little or no role in this response can be ascribed to reduced active vasodilator activity. PMID- 1928402 TI - Splanchnic vasoconstriction and bacterial translocation after thermal injury. AB - Gut barrier failure and bacterial translocation (BT) after thermal injury may result from splanchnic vasoconstriction and intestinal ischemia. The role of the renin-angiotensin system in intestinal blood flow and BT after thermal injury was studied by pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril in Wistar rats before sham or 30% scald burn. Adequacy of ACE inhibition was documented by the absence of a hypertensive response to angiotensin I, and intestinal blood flow was determined using 51Cr-labeled microspheres. Small bowel blood flow was decreased by 46% at 4-h postburn (P less than 0.05) in untreated burned animals despite maintenance of normal cardiac index but returned to baseline levels by 24 h after injury. Enalapril pretreatment resulted in maintenance of small bowel blood flow after thermal injury and was associated with a significantly reduced incidence of BT (20% vs. 75% in untreated burned animals, P less than 0.01). These findings further implicate intestinal ischemia in the etiology of gut barrier dysfunction after thermal injury, mediated in part by activation of the renin-angiotensin system. PMID- 1928403 TI - Albumin outflow into deep cervical lymph from different regions of rabbit brain. AB - Dynamics and pathways of 125I-labeled albumin (RISA) outflow from brain to deep cervical lymph have been studied in anesthetized rabbits between 4 and 25 h after microinjection of 1 microliter RISA into the internal capsule or midbrain. Lymph from the jugular lymph trunks was collected for periods of 2-11 h. RISA was cleared from brain with half-times of disappearance from internal capsule and midbrain of 18.2 and 11.9 h, respectively. RISA was distributed in high concentration to subarachnoid arteries that supplied the tissue injection site; this was consistent with RISA drainage from brain via perivascular spaces. Outflow through lymph rose to a maximum value 15-20 h after tracer injection. Mean recovery of RISA from lymph over the 25-h collection period accounted for 22% of total loss from internal capsule and 18% from midbrain. This result compares with mean recoveries from caudate nucleus and cerebrospinal fluid of 47% and 30%, respectively [M.W.B. Bradbury, H.F. Cserr, and R.J. Westrop, Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9): F329-F336, 1981]. These are minimal estimates of total outflow to lymph because of the 15- to 20-h delay in RISA passage from brain to lymph. PMID- 1928404 TI - Dominance of colloid osmotic pressure in renal excretion after isotonic volume expansion. AB - Studies were carried out in unanesthetized dogs to determine the relative importance of neural, endocrine, and colloid osmotic pressure (COP) in the diuretic and natriuretic responses associated with volume expansion. Renal excretory responses to 30-min intravenous infusions of isotonic saline (400 ml) or whole blood (100 ml) were compared while various controllers of sodium and water excretion were either eliminated or held constant. Dogs were studied in the normal state; with plasma arginine vasopressin (AVP) fixed by intravenous infusion; with bilateral renal denervation and plasma AVP fixed; renal denervated with plasma AVP, angiotensin II, aldosterone, atrial natriuretic factor fixed; and renal denervated with these same hormones fixed and with renal arterial pressure servo-controlled at a constant level. Normal uncontrolled dogs increased sodium and water excretion nearly fourfold by the end of the saline load and excreted 85% of the load within 5 h. Urine excretion was minimally affected when the various neural and endocrine controllers were fixed or eliminated. There were no changes of mean arterial pressure with the saline volume loads, but COP fell 2.5 mmHg. Equivalent expansion of the blood volume (100 ml) with whole blood in which COP was unchanged resulted in nearly no increase of urine excretion in renal-denervated dogs with plasma hormones fixed and renal perfusion pressure held constant. We conclude that the rapid diuresis and natriuresis following isotonic volume expansion is predominantly a result of plasma protein dilution and a reduction of COP. PMID- 1928405 TI - Transfer function analysis of the circulation: unique insights into cardiovascular regulation. AB - We have demonstrated previously that transfer function analysis can be used to precisely characterize the respiratory sinus arrhythmia (RSA) in normal humans. To further investigate the role of the autonomic nervous system in RSA and to understand the complex links between respiratory activity and arterial pressure, we determined the transfer functions between respiration, heart rate (HR), and phasic, systolic, diastolic, and pulse arterial pressures in 14 healthy subjects during 6-min periods in which the respiratory rate was controlled in a predetermined but erratic fashion. Pharmacological autonomic blockade with atropine, propranolol, and both, in combination with changes in posture, was used to characterize the sympathetic and vagal contributions to these relationships, as well as to dissect the direct mechanical links between respiration and arterial pressure from the effects of the RSA on arterial pressure. We found that 1) the pure sympathetic (standing + atropine) HR response is characterized by markedly reduced magnitude at frequencies greater than 0.1 Hz and a phase delay, whereas pure vagal (supine + propranolol) modulation of HR is characterized by higher magnitude at all frequencies and no phase delay; 2) both the mechanical links between respiration and arterial pressure and the RSA contribute significantly to the effects of respiration on arterial pressure; 3) the RSA contribution to arterial pressure fluctuations is significant for vagal but not for sympathetic modulation of HR; 4) the mechanical effects of respiration on arterial pressure are related to the negative rate of change of instantaneous lung volume; 5) the mechanical effects have a higher magnitude during systole than during diastole; and 6) the mechanical effects are larger in teh standing than the supine position. Most of these findings can be explained by a simple model of circulatory control based on previously published experimental transfer functions from our laboratory. PMID- 1928406 TI - Depolarization modulates endothelial cell calcium influx and microvessel permeability. AB - We investigated the mechanisms whereby high-potassium (57.9 mM) Ringer solutions attenuate the increase in permeability caused when microvessels are exposed to the calcium ionophores ionomycin and A23187 (5 microM). In single perfused microvessels we measured cytoplasmic calcium concentration, [Ca2+]i, in the cells forming the microvessel wall and the hydraulic conductivity, Lp, to follow changes in the permeability of the microvessel walls. In normal Ringer solution, [Ca2+]i was increased to an initial peak value of 226 +/- 12 nM after exposure to calcium ionophores; the corresponding increase in microvessel Lp was 10.3 +/- 2.6 times control. With high-potassium solutions, the peak value of [Ca2+]i was 133 +/- 12 nM and Lp was increased to only 2.5 +/- 0.7 times control. Increasing extracellular calcium from 1.1 to 5 mM with high potassium restored the initial peak value of [Ca2+]i to 303 +/- 38 nM. The increases in both [Ca2+]i and Lp were abolished in calcium-free solutions. If high-potassium solutions depolarize the cells forming the microvessel wall as indicated by the membrane potential sensitive dye bisoxonol, then the magnitude of the initial increase in [Ca2+]i could be accounted for by changes in the electrochemical driving force through conductive channels for calcium ion. Our results conform to the hypothesis that the permeability properties of microvessels are modulated by changes in the membrane potential of the endothelial cells and/or pericytes forming the microvessel wall. PMID- 1928407 TI - Inhibition of elastolysis by SC-37698 reduces development and progression of monocrotaline pulmonary hypertension. AB - Our previous studies showed that increased pulmonary artery elastolytic activity is associated with monocrotaline-induced pulmonary hypertension in rats, and the latter is reduced by the elastase inhibitor SC-39026. This agent, given orally, decreases monocrotaline-induced muscularization of normally nonmuscular peripheral arteries but not medial hypertrophy of muscular arteries. To establish whether constant infusion of an elastase inhibitor would reduce both vascular lesions induced by monocrotaline injection, SC-37698 (an analogue of SC-39026) was given intravenously by osmopump. To separately assess whether SC-37698 would inhibit development of the vascular changes as well as their progression, SC 37698 or vehicle was infused for the first 2 wk (2-wk study) or was delayed until 1 wk after monocrotaline injection (3-wk study). Hemodynamic data were recorded from indwelling catheters, and the lungs were evaluated morphologically. Saline injected control rats given SC-37698 or vehicle were similar at both time points. Monocrotaline-injected rats given SC-37698 compared with those given vehicle alone had lower pulmonary artery pressures, 17.9 +/- 0.5 vs. 23.7 +/- 0.8 mmHg (P less than 0.01) in the 2-wk study and 24.0 +/- 1.8 vs. 33.5 +/- 3.1 mmHg (P less than 0.05) in the 3-wk study. This was associated with significant decreases in muscularization of peripheral arteries and reductions in medial hypertrophy of muscular arteries. In the hilar pulmonary arteries assessed at 3 wk only, SC 37698 significantly decreased monocrotaline-induced endothelial injury, subendothelial edema, migration of smooth muscle cells into subendothelium, medial hypertrophy, collagen accumulation, and abnormal distribution of elastin as interlamellar islands. Pulmonary artery elastolytic activity was reduced in SC 37698-treated compared with untreated monocrotaline-injected rats (P less than 0.05). Thus infusion of SC-37698 reduces monocrotaline-induced pulmonary hypertension when administered before or even after development of early vascular changes. PMID- 1928408 TI - Effect of graded umbilical cord compression in fetal sheep at 0.6-0.7 gestation. AB - To define responses of immature fetuses to asphyxia, we occluded the umbilical cord of 11 chronically instrumented fetal sheep at 82-94 days gestation and measured hemodynamic and catecholamine responses. The fetuses became acidemic, hypoxemic, and hypercarbic: arterial pH and PO2 decreased from 7.36 +/- 0.04 and 22 +/- 3 Torr to 7.10 +/- 0.04 (mean +/- SD, P less than 0.01) and 15 +/- 4 Torr (P less than 0.01), respectively, and PCO2 increased from 56 +/- 5 to 86 +/- 8 Torr (P less than 0.01) when umbilical blood flow was reduced by 75-88%. This degree of reduction in umbilical blood flow decreased cardiac output from 606 +/- 101 to 247 +/- 67 ml.min-1.kg-1 (P less than 0.01) and blood flow to hepatic, renal, musculoskeletal, and pulmonary vascular beds. Plasma norepinephrine concentrations increased from 1,557 +/- 975 to 16,718 +/- 14,672 pg/ml (P less than 0.05) with a 75-88% reduction, but mean arterial blood pressure did not increase. The absence of a hypertensive response probably relates to the decrease in cardiac output. These data indicate that asphyxia severely compromises cardiac output and organ perfusion in the midgestation fetus. PMID- 1928410 TI - Modeling the dynamic interaction between left ventricle and intra-aortic balloon pump. AB - An analog model is developed to characterize how alterations of some intra-aortic balloon pump (IABP) parameters affect the coupling between left ventricle (LV) and aorta. The time-varying elastance concept is applied to modeling both active components (LV and IABP) in the assisted circulation. Pressure and flow waveforms in the system are determined by numerically integrating five simultaneous state equations that represent the system dynamics. Validity of the model is supported by good agreement between model predictions and published data on LV pressure volume (P-V) loops, end-systolic P-V relations, and hemodynamic consequences of adjusting IABP timing and speed. The model also predicts that increasing balloon volume increases the diastolic aortic pressure augmentation but has a negative effect of increasing LV load. Increasing balloon diameter over length ratio and holding a constant volume increases the diastolic augmentation and decreases the LV demand. Positioning the balloon closer to the heart improves systolic unloading but affects neither diastolic augmentation nor cardiac output. These results suggest that occlusivity is a major determinant of IABP effectiveness and plays a more important role than balloon volume and position. PMID- 1928409 TI - Effect of pregnancy on endothelium and smooth muscle: their role in reduced adrenergic sensitivity. AB - During pregnancy, vascular reactivity of the uterine artery is characterized by decreased contraction to norepinephrine and increased relaxation to acetylcholine. We investigated whether 1) relaxation to A23187 is increased during pregnancy and 2) endothelium-derived relaxing factor (EDRF) and/or prostaglandins are responsible for the decreased uterine artery sensitivity to norepinephrine during pregnancy. Isolated rings of uterine and carotid arteries were obtained from pregnant and nonpregnant guinea pigs. Relaxation to sodium nitroprusside in uterine but not carotid artery was reduced during pregnancy. Relaxation of both uterine and carotid arteries to the calcium ionophore A23187 was unaffected by pregnancy. During pregnancy, contractions to norepinephrine were reduced in the uterine artery compared with arteries from nonpregnant animals. Indomethacin slightly enhanced the contractions of uterine artery to norepinephrine during pregnancy. However, indomethacin-treated uterine arteries from pregnant animals were still less responsive to norepinephrine than control uterine arteries from nonpregnant animals. Methylene blue enhanced the efficacy of norepinephrine in uterine arteries of nonpregnant animals as well as carotid arteries of pregnant and nonpregnant animals but not in uterine arteries of pregnant animals. In contrast, N-monomethyl-L-arginine, a specific inhibitor of EDRF synthesis, not only enhanced uterine and carotid artery responses to norepinephrine in both pregnant and nonpregnant animals but fully reversed the blunted potency of norepinephrine on uterine arteries of pregnant to that of nonpregnant animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928411 TI - A technique for production of complete atrioventricular block in dogs. AB - A simple and reliable technique for producing complete atrioventricular (AV) block in dogs by the injection of a 38% formaldehyde solution into the area of the AV node is described. This technique, a modification of previous methods utilizing formaldehyde injection for the production of complete AV block, uses the coronary sinus as the major landmark. Complete heart block was produced in 20 of 20 dogs. The technique is simple and associated with few problems, does not require special equipment, is associated with little or no hemorrhage from the injection site, and does not enter a cardiac chamber. The only side effect noted was the development of ventricular arrhythmias in 2 of 20 dogs. A detailed description of the technique is included with comparisons to previous techniques utilizing injection of a 40% formaldehyde solution. PMID- 1928412 TI - Neutrophil passage through isolated perfused rabbit lungs. AB - Kinetics of polymorphonuclear leukocyte (PMN) lung passage were investigated in ex vivo isolated and ventilated left rabbit lungs, perfused with buffer solution at physiological flow rate. 111In-labeled PMNs of rabbit or human origin were injected into the pulmonary artery, and the first fraction of PMNs that rapidly passed the lung together with coinjected erythrocytes, was collected separately for external radioactivity counting. Washout of initially retained PMNs from the lung was monitored by use of a sodium-iodide detector. Recirculation of cells was avoided by insertion of a filter in the perfusion circuit. A fraction of 16.6 +/- 1.3% of rabbit PMNs rapidly passed the lung vasculature, followed by an exponential washout of initially retained PMNs [half-time (t50) of lung transit 8.1 +/- 0.6 min]. Slightly higher t50 (12.2 +/- 1.0 min) was obtained upon use of human PMNs. Reduction in flow by 50% caused a marked prolongation of PMN transit (t50 = 27.8 +/- 5.1 min), whereas increase in flow to 150% only insignificantly decreased t50. Rise in pulmonary venous pressure to 5 and 8 mmHg caused retardation of PMN lung transit (t50 = 15.3 +/- 0.6 and 31.6 +/- 3.6 min). Preincubation of PMNs with 2 ng/ml endotoxin for 1 h induced marked delay in PMN washout (t50 = 26.1 +/- 2.8 min). In conclusion, single-pass PMN kinetics in isolated lungs correspond to in vivo studies previously reported, thus allowing elucidation of PMN-endothelial interactions in an intact lung vasculature under standardized conditions. PMID- 1928413 TI - Peripheral lymphatic cannulation for physiological analysis of interstitial fluid compartment in humans. AB - Analysis of peripheral interstitial concentrations of hormones or substrates in humans has undoubtedly been hampered by the difficulty in performing retrograde peripheral lymphatic cannulation and obtaining adequate flow rates of lymph. We now describe a technique for direct continuous sampling of peripheral lymph. A lymphatic vessel was cannulated in the lower legs of 14 males, and lymph was collected for 24-48 h. Adequate quantities of lymph were obtained basally and during physiological manipulations to make collections at 15-min intervals. Flow rates averaged 1.84 ml/h and ranged from 0.34 to 4.96 ml/h. We conclude that peripheral lymphatic vessels can be cannulated and flow rates are sufficient to measure interstitial concentration of hormones or substrates both at steady state and dynamically in adult humans. PMID- 1928414 TI - Simultaneous measurement of contraction and oxygen consumption in cardiac myocytes. AB - A setup has been developed that simultaneously measures the mechanics and the energetics of electrically induced contractions at physiological frequencies of isolated cardiac myocytes. The core of the setup is a self-manufactured stimulation chamber in which most of the myocytes are in suspension while some are attached to a plastic cover slip prepared from culture Petri dishes. The analysis of the contractile behavior of the attached myocytes is based on an image-processing system with digitized frames of a charge-coupled device camera. Thirty-six frames illuminated by a stroboscope are taken at increasing time intervals between stimulus and flash (snap), allowing one to resolve the contraction cycle with a very high time resolution (down to 1 ms). The number of pixels that differ between each of these frames and a "reference" frame of the cells in the relaxed state (slack cell length) are used to quantify the contractions. An oxygen electrode in the chamber registers the drop of oxygen tension resulting from the consumption by the myocytes, which exhibit a strictly aerobic metabolism. The resulting data are also stored and analyzed in an IBM-AT compatible computer. PMID- 1928415 TI - A new approach to in situ left ventricular volume clamping in dogs. AB - Major contributing factors modulating left ventricular (LV) diastolic behavior are active relaxation of myocardium and volume change during filling, the interaction of which complicates analysis of diastolic pressure-volume relationship, especially in early diastole. To separate the effect of active relaxation and filling, a method was introduced [E. L. Yellin, M. Hori, C. Yoran, E. H. Sonnenblick, S. Gabbay, R. W. M. Frater, Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H620-H629, 1986] to interrupt mitral inflow and keep LV volume constant throughout diastole. Their preparation requires replacing the mitral valve with an artificial valve using cardiopulmonary bypass, which might cause significant change in cardiac performance or produce detrimental systemic effects. We developed a new volume-clamping method that preserves the native mitral valve and apparatus intact and avoids cardiopulmonary bypass. A modified Bjork-Shiley prosthetic valve (20 mm orifice diam) in a special mounting ring was placed above the native mitral valve through the left atrium and secured from outside the heart. This prosthetic valve was controlled by a cable connected to solenoids outside the dog, triggered by the electrocardiogram or other physiological signal. We compared our method (n = 7) with that of Yellin et al. (n = 2) in nine random source dogs. In our method, no end-diastolic pressure gradient or regurgitant pressure wave was observed, and the prosthetic valve did not disturb movement of the native mitral valve. When the prosthetic valve was forced to a closed position at end systole, LV volume, measured with a conductance catheter, was maintained at or near end-systolic volume throughout diastole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928416 TI - Effect of pentoxifylline in rabbit pulmonary circulation: influence of age and vasomotor tone. AB - We determined the influence of vasomotor tone and age on pentoxifylline (PTX) effects in rabbit lungs. Lungs of adult, juvenile, and neonatal rabbits were isolated and perfused with blood at constant flow in zone 3. In adult lungs only, pressures were measured in 20- to 50-microns-diameter subpleural arterioles and venules (by micropuncture) to partition the circulation into arteries, microvessels, and veins during baseline, after PTX infusion (20 mg/kg), and terminally, after treatment with papaverine. In some adult and juvenile lungs, vasomotor tone was elevated with KCl, and some adult lungs were pretreated with indomethacin to inhibit cyclooxygenase. We found that PTX's vasodilator effect was influenced by age; it was approximately 52, approximately 65, and approximately 82% as effective as papaverine in untreated neonatal, juvenile, and adult lungs, respectively, and approximately 49 and approximately 93% as effective as papaverine in KCl-constricted adult and juvenile lungs, respectively. The site(s) of PTX action depended on basal vasomotor tone; in lungs with moderate tone, PTX dilated arteries only, and in lungs with high tone, PTX dilated both arteries and veins. Cyclooxygenase inhibition did not attenuate PTX effects. We conclude that, in rabbit lungs, PTX dilates arteries and veins and that the magnitude of PTX effect is dependent on age and basal vasomotor tone. PMID- 1928417 TI - Nocturnal variations in peripheral blood flow, systemic blood pressure, and heart rate in humans. AB - Subcutaneous adipose tissue blood flow rate, together with systemic arterial blood pressure and heart rate under ambulatory conditions, was measured in the lower legs of 15 normal human subjects for 12-20 h. The 133Xe-washout technique, portable CdTe(Cl) detectors, and a portable data storage unit were used for measurement of blood flow rates. An automatic portable blood pressure recorder and processor unit was used for measurement of systolic blood pressure, diastolic blood pressure, and heart rate every 15 min. The change from upright to supine position at the beginning of the night period was associated with a 30-40% increase in blood flow rate and a highly significant decrease in mean arterial blood pressure and heart rate (P less than 0.001 for all). Approximately 100 min after the subjects went to sleep an additional blood flow rate increment (mean 56%) and a simultaneous significant decrease in mean arterial blood pressure (P less than 0.001) were observed. The duration of this hyperemic phase was 116 min. A highly significant reduction of the subcutaneous vascular resistance (50%) was demonstrated during the hyperemic blood flow rate phase compared with the surrounding phases (P less than 0.0001). The synchronism of the nocturnal subcutaneous hyperemia and the decrease in systemic mean arterial blood pressure point to a common, possibly central nervous or humoral, eliciting mechanism. PMID- 1928418 TI - Adriamycin-induced myocardial dysfunction in vitro is mediated by free radicals. AB - The role of free radicals in adriamycin (Adr)-induced acute myocardial changes was examined by using different antioxidants. Exposure of papillary muscles to Adr (100 microM) in a tissue bath for 60 min reduced developed force by 42%, increased lipid peroxidation by 200%, and resulted in characteristic ultrastructural changes. Catalase (4 x 10(4) U/l), an enzyme effective in the hydrolysis of hydrogen peroxide (H2O2), was more effective in maintaining the developed force than mannitol (20 mM), a hydroxyl radical scavenger. A small protection of developed force seen with superoxide dismutase (1.2 x 10(5) U/l), a quencher of superoxide radical, was evident for the first 15 min only. Only catalase and mannitol showed significant protection against Adr-induced increase in lipid peroxidation. Ultrastructural changes due to Adr alone included mitochondrial swelling, intramitochondrial granules, vacuolization, and disruption of sarcomeres. All of these changes were reduced in the presence of both catalase and mannitol, whereas superoxide dismutase was without any effect. Complete structural or functional protection was not seen with any of the antioxidants used in the study. Although both H2O2 and hydroxyl radical appear to be involved in Adr-induced deleterious effects, data on developed force also indicate that H2O2 may have a major role in mediating the acute effects of Adr in vitro. PMID- 1928419 TI - Mercury from dental "silver" tooth fillings impairs sheep kidney function. AB - In humans Hg vapor is released from "silver" amalgam fillings that contain 50% Hg by weight. Previous studies show that when 12 such fillings are placed in sheep teeth, the kidneys will concentrate amalgam Hg at levels ranging from 5 to 10 micrograms Hg/g renal tissue 4-20 wk after placement. In the present study 12 occlusal fillings were placed in each of six adult female sheep under general anesthesia, using standard dental procedures. Glass ionomer occlusal fillings (12) were inserted in two control sheep. At several days before dental surgery, and at 30 and 60 days after placement of fillings, renal function was evaluated by plasma clearance of inulin and by plasma and urine electrolytes, urea, and proteins. An average plasma inulin clearance rate of 69.5 +/- 7.2 ml/min before amalgam placement was reduced to 32.3 +/- 8.1 ml/min by 30 days and remained low at 27.9 +/- 8.7 ml/min after 60 days. Inulin clearance did not change in controls. After amalgam placement urine concentration of albumin decreased from 93.0 +/- 20.5 to 30.1 +/- 15.3 mg/l and urine Na+ concentration increased steadily from 24.8 +/- 7.7 to 82.2 +/- 20.3 mmol/l at 60 days. Concentrations of K+, urea, gamma-glutamyl transpeptidase, alkaline phosphatase, and total protein did not change significantly from 0 to 60 days in urine. Plasma levels of Na+, K+, urea, and albumin remained unchanged from 0 to 60 days after amalgam. Renal histology remained normal in amalgam-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928420 TI - Diurnal rhythms in fetal urine flow, vascular pressures, and heart rate in sheep. AB - Conflicting indirect data exist as to whether diurnal variations occur in fetal urine flow rate. In addition, the extent of diurnal rhythms in fetal venous pressure or arterial pressure is unknown, although 24-h rhythms do exist in fetal heart rate. In the present study, we used on-line computer techniques to continuously monitor these variables in chronically catheterized ovine fetuses. Fetal urine flow rate and vascular pressures were successfully recorded in 6 of 11 animals over a 24-h period on 21 days out of a total of 45 days of monitoring. We found highly significant diurnal variations in fetal urine flow rate (P less than 10(-6). Hourly means displayed a maximum at 2130 h and a minimum at 1330 h with a maximum amplitude of 28 +/- 5% of the 24-h mean. A secondary maximum (at 0630 h) and minimum (at 0330 h) of smaller amplitude also occurred. There were simultaneous and highly significant (P less than 0.0001) diurnal rhythms in fetal arterial pressure (+/- 2%), venous pressure (+/- 7%), and heart rate (+/- 5%). The maxima in arterial pressure and heart rate occurred within 1 h of the maximum in urine flow, while venous pressure changes were opposite those in arterial pressure. Hourly mean urine flow correlated significantly with arterial pressure but not venous pressure or heart rate, suggesting that the observed 24-h variations in fetal urine flow rate may be partially mediated by a pressure diuresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928421 TI - Vasopressin and oxytocin secretion in chronically hyposmolar rats. AB - Neurohypophysial secretion of vasopressin (AVP) and oxytocin (OT) was studied in rats maintained under hyposmolar conditions for 10-24 days. Graded intravenous infusions of hypertonic saline solutions had no consistent effect on plasma AVP and OT levels until plasma sodium concentration ([Na+]) exceeded 130 mM, after which levels of both hormones increased as an exponential function of plasma [Na+]. Detectable increases in plasma AVP and OT began at significantly lower plasma [Na+] in hyposmolar rats than in normosmolar control rats (10.8 mM lower for AVP and 18.4 mM lower for OT). AVP and OT secretion in hyposmolar rats was also markedly blunted in response to nonosmotic stimuli, including acute and chronic hypovolemia and systemic administration of cholecystokinin. Cessation of 1-desamino-8-D-arginine vasopressin-induced antidiuresis resulted in an appropriately rapid correction of plasma [Na+] to normal levels within 24 h. Consequently, although chronic hyposmolarity caused a moderate downward resetting of the osmotic thresholds for AVP and OT secretion, it did not cause sustained deficits in osmoregulation. These results suggest that osmoreceptor activity is regulated to maintain extracellular fluid and plasma osmolality within narrow absolute ranges rather than responding to relative changes in osmolality. PMID- 1928422 TI - Enhanced drinking after excitotoxic lesions of the parabrachial nucleus in the rat. AB - Previous reports indicate the lateral parabrachial nucleus (IPBN) is important in the regulation of fluid intake. After electrolytic lesions of the IPBN, rats consume increased amounts of water when challenged with pharmacological stimuli that mimic depletion of the extracellular fluid space. Nonetheless, it is possible that neurons within the IPBN are not responsible for the overingestion of water during extracellular thirst challenges, since electrolytic lesions damage fibers of passage as well as neurons within the IPBN. Thus we used the excitatory neurotoxin ibotenic acid to lesion cell bodies within the IPBN. After recovery from surgery, water consumption by lesioned rats was significantly greater than consumption by vehicle or uninjected control rats when challenged with subcutaneous angiotensin II or isoproterenol to stimulate drinking. However, when injected with subcutaneous hypertonic saline to produce cellular dehydration, or when water deprived for 24 h, the water intake of rats with lesions was not different from the intake of control rats. Anatomical examination of the lesion sites revealed that ibotenic acid injection caused a notable loss of neurons in the IPBN with little or no damage to surrounding structures. Moreover, injection of an anterograde tracer into the dorsomedial medulla resulted in labeling of fibers that traverse the ibotenic acid lesion site. Together, these data suggest neurons within the IPBN are involved in the regulation of fluid intake, particularly challenges that involve depletion of the extracellular fluid space. PMID- 1928423 TI - The adenosine receptor blocker aminophylline increases anoxic ethanol excretion in crucian carp. AB - By depressing energy consumption, anoxia-tolerant animals are thought to compensate for a reduced ability to produce energy during anoxia. Adenosine is an inhibitory neuromodulator in vertebrates and, hence, has the potential ability to depress energy consumption. Ethanol is the main metabolic end product in anoxic Carassius, and the present study shows that the rate of ethanol excretion in anoxic crucian carp (Carassius carassius L.) can be increased threefold by treatment with the adenosine receptor antagonist aminophylline (75 mg/kg). By contrast, the same dose of aminophylline did not increase the rate of routine oxygen consumption during normoxia. It is hypothesized that adenosine acts as a metabolic depressant during anoxia in crucian carp. PMID- 1928424 TI - Adaptations to chloride-depletion alkalosis. AB - The systemic and renal adaptations for the maintenance and correction of metabolic alkalosis generated by chloride depletion (CDA) are the focus of this review. The hypothesis that extracellular fluid (ECF) volume expansion is essential for the correction of CDA is refuted, while the concept that Cl- repletion is necessary and sufficient for correction is developed. Contraction of ECF volume probably can occur as a consequence of CDA. The principal mechanisms by which the kidney corrects CDA appear to reside primarily in the collecting duct, which is endowed with the anion exchange mechanisms and the capacity to effect the necessary changes in body anion composition. Although the remainder of the collecting duct is undoubtedly important in this response, the cortical segment appears to have the paramount role since it can either absorb or secrete HCO3-. Alterations in the delivery of Cl- or HCO3- to the collecting duct may also be important but changes in glomerular filtration rate appear to have a minor role. Major unanswered questions in the pathophysiology of CDA are the manner in which exogenous Cl- repletion is detected and the kidney is signaled to excrete HCO3- and the cellular mechanisms by which this is accomplished in the various nephron segments. PMID- 1928425 TI - Defective cerebral glucose utilization in diet-induced obese rats. AB - A neural mechanism may underlie the divergent weight gain patterns of rats fed a high-energy diet; half develop diet-induced obesity (DIO), whereas the rest are diet resistant (DR). Male rats were fed chow (n = 14) or a high-energy diet for 3 mo with the development of DIO (n = 11) or DR (n = 12). DIO rats had 159-219% heavier retroperitoneal fat pads and 158% higher plasma insulin levels than chow fed and DR rats, but plasma glucose levels were equal. Rats were trained to drink glucose after an overnight fast and were tested for local cerebral glucose utilization using 2-deoxy-D-[14C]glucose autoradiography in the presence or absence of 0.15% saccharin substituted for glucose. Saccharin intake increased 2 deoxyglucose uptake in the rostral nucleus tractus solitarius of DR but not DIO or chow-fed rats. Also, DIO rats had reduced basal 2-deoxyglucose uptake in the central amygdaloid nucleus. High-energy diet intake was associated with saccharin induced depression of 2-deoxyglucose uptake in the inferior olive and increased utilization in the medial amygdaloid nucleus of both DR and DIO rats. Thus DIO rats have diminished basal and food-related neuronal activity in certain brain areas involved in food intake and autonomic function. Furthermore, dietary content affects glucose utilization in areas not usually associated with these functions. PMID- 1928426 TI - Dietary regulation of intestinal brush-border sugar and amino acid transport in carnivores. AB - The ability of omnivores and herbivores to regulate reversibly their intestinal brush-border nutrient transporters is functionally related to the unpredictably variable composition of their natural diets. To determine whether carnivores are able similarly to regulate the activities of their intestinal nutrient transporters, we fed to three species of vertebrates that are carnivorous as adults (cats, mink, and leopard frogs) diets with either at least 50% digestible carbohydrate or with negligible carbohydrate levels. Rates of transport for the sugars glucose and fructose and the amino acids (AAs) aspartate, leucine, lysine, and proline were measured throughout the intestine (only proline and glucose in the frogs) by an in vitro everted-sleeve method. Although all three species consume much carbohydrate during early development, only the mink was able to regulate sugar transporter activity in response to changes in levels of dietary carbohydrate. In contrast, the sugar transporters of the cat were unresponsive to varying carbohydrate levels, and long-term feeding of a high-carbohydrate diet caused down-regulation of sugar transport in frogs. Of the three species, only the mink is a member of a family that includes omnivorous species, whereas all members of the families to which the cat and frog belong are carnivorous as adults. All three species were able to regulate rates of AA transport, though the patterns and magnitude of the responses differed between species as well as between AAs, suggesting independent regulation of some AA transporters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928427 TI - Changes in small intestinal mucosa morphology and cell renewal in suckling, prolonged-suckling, and weaned lambs. AB - No information concerning the effect of weaning on intestinal cell proliferation is currently available in large species with early intestinal morphogenesis, a group including most domestic animals and humans. Changes in intestinal morphology and epithelial cell renewal were investigated in 1-, 5-, and 8-wk-old suckling and 8-wk-old weaned lambs after injection of [3H]thymidine. In suckling lambs a gradual increase in crypt depth occurred with age, especially in the proximal intestine, whereas villus height was significantly reduced in the distal regions. At 8 wk of age weaned and prolonged-suckling lambs exhibited no significant differences in crypt depth throughout the intestine and in villus height proximally. However, weaned lambs had shorter villi in the jejunum and ileum. The highest enterocyte migration rates (4.4-9.7 microns/h) were observed in 1-wk-old lambs. In suckling animals, migration rates decreased with age by 60, 51, and 11% in the duodenum, jejunum, and ileum, respectively. Weaned and prolonged-suckling 8-wk-old lambs had a similar rate of enterocyte migration in the ileum. Furthermore, ruminating animals exhibited only slightly higher migration rates in the duodenum and the jejunum (53 and 15%, respectively). In suckling lambs, epithelial cell renewal required 2.1-4.0, 4.5-6.3, and 4.0-5.3 days at 1, 5, and 8 wk of age, respectively, whereas labeled cells reached the tips of the villi within 3.0-3.1 days in weaned animals. These data suggest that the suckling period corresponds to a gradual and important phase of postnatal intestinal adaptation in the sheep, a species with early patterns of intestinal cell replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928428 TI - Restricted feeding entrains circadian wheel-running activity rhythms of the kowari. AB - The effect of daily restricted feeding (RF) on the circadian wheel-running rhythms of the kowari, Dasyuroides byrnei, was examined in two experiments. Kowaris were presented with a preferred food (determined in a pilot study) during a daily 2-h meal in the light period of a 14:10 light-dark (LD) cycle (expts 1 and 2), during constant dark (DD) immediately after termination of the LD cycle (expt 1), and during DD when kowaris were free running (expt 1). Results showed that 1) RF elicited anticipatory activity similar in duration and phasing to that observed in the rat; 2) cycles of meal-associated activity free ran for up to 6 days after the termination of RF; 3) activity persists at a phase near that of the former mealtime during periods of food deprivation; and 4) activity indicative of beating between two pacemakers occurred when feeding was restricted to the L period of LD cycles. Together these observations suggest that the activity rhythms of the kowari may be controlled by separate, but possibly coupled, light-entrainable and food-entrainable pacemakers, as are those of the rat. PMID- 1928429 TI - Prostanoids attenuate pial arteriolar dilation induced by cortical spreading depression in rabbits. AB - The role of prostanoids in mediating cerebrovascular responses to cortical spreading depression (CSD) was examined in anesthetized rabbits. CSD was elicited by KCl microinjection, and its propagation was monitored electrophysiologically. Pial arterial diameter was determined using a closed cranial window and intravital microscopy, and regional cerebral blood flow (rCBF) was determined using laser flowmetry. Levels of peri-arachnoid cerebrospinal fluid prostanoids were determined by radioimmunoassay. CSF increased pial arteriolar diameter 62% and rCBF 354% over the baseline levels. Locations of propagating CSD, dilating pial arteriole, and increased rCBF were always closely associated spatiotemporally. Cerebrospinal fluid prostanoid levels increased during single CSD-induced arteriolar dilation, and they were further augmented during multiple CSDs. Indomethacin enhanced both CSD-induced vasodilation (88%) and rCBF increase (580%), but it decreased the cerebrospinal fluid levels of prostanoids below the baseline levels and prevented their increase during CSD-induced vasodilation. These results indicate that prostanoids are synthesized from neurons or glial cells and/or the brain vessels and, as the net result, counteract pial arteriolar dilation and rCBF increase during CSD. In addition, they support the hypothesis that the vasodilation is caused primarily by neurogenic factors associated with CSD. PMID- 1928430 TI - Diurnal responses of mammals to acute exposure to a hyperdynamic environment. AB - Acute exposure to hyperdynamic environments elicits significant depressions in core temperature in both diurnal squirrel monkeys and nocturnal rats. This study describes time of day variations in core temperature responses in squirrel monkeys and rats exposed for 70 min to a hyperdynamic environment (2 g) produced via centrifugation. Experiments were performed during the middle of the light or dark phase. After a 70-min control period, squirrel monkey resting core temperature was 38.6 +/- 0.2 (SE) and 36.8 +/- 0.2 degrees C during the day and night, respectively. At the end of a 7-min exposure to 2 g, squirrel monkey core temperature decreased 1.3 +/- 0.2 degree C during the day but remained a constant 36.8 +/- 0.4 degrees C at night. Core temperature of rats exposed to an identical 70-min 2 g profile decreased 1.5 +/- 0.4 degree C from a resting 37.1 +/- 0.6 degrees C during the day and 2.3 +/- 0.2 degrees C from a resting 37.8 +/- 0.3 degrees C at night. Thus, in both species, there were clear day-night differences in response to hyperdynamic environments, with the greatest fall in core temperature occurring during the animal's active period. PMID- 1928431 TI - Dietary obesity and weight cycling in rats: a model of stress-induced hypertension? AB - The present study was designed to reproduce the mild hypertension seen in dietary obese weight-cycled rats [P. Ernsberger and D. O. Nelson. Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23): R47-R55, 1988] and determine whether this mild hypertension was associated with changes in sodium excretion and pressor responsiveness to angiotensin II (ANG II). Male Sprague-Dawley rats were fed pelleted chow (Pellet group) or chow plus sweetened condensed milk (Milk group) or were exposed to four cycles of a 4-day fast alternated with 2 wk of refeeding of pelleted chow and sweetened condensed milk (Cycled group). Blood pressure and heart rate were measured by tail cuff at the onset and last day of each fast and after 3 days of refeeding. During fasting, urine sodium excretion was measured. Mean arterial pressure and heart rate responses to intravenous administration of ANG II (40, 80, and 120 ng/kg), metoprolol (1 mg/kg), and methyl scopolamine (2 mg/kg) were obtained from the femoral artery in awake unrestrained rats. Weight cycling did not lead to mild hypertension or increased bradycardic response to sympathetic blockade with metoprolol. ANG II-elicited pressor responses were similar for Pellet, Milk, and Cycled groups. Sodium excretion did not change with fasting. Mild hypertension developed when obese weight-cycled rats were housed together in groups and not when housed individually. Our preliminary data are consistent with the notion that stress associated with group housing may be a factor in the mild hypertension of obese weight-cycled rats. PMID- 1928432 TI - Studies on binding sites, contents, and effects of AVP in isolated bladder and urethra from rabbits and humans. AB - The binding sites, contents, and effects of arginine vasopressin (AVP) were studied in isolated bladder and urethral preparations from rabbits and humans. In all tissues, higher levels of AVP-like immunoreactivity (AVP-LI) were detected than those normally found in plasma. Radioligand membrane binding studies using [3H]AVP as the ligand revealed the existence of a single population of binding sites in the rabbit bladder, and displacement experiments indicated that the receptor was of the V1 subtype. By autoradiography, [3H]AVP binding sites in the rabbit bladder were shown to be located on both circularly and longitudinally oriented smooth muscle cells, as well as in the submucosa at the part adjacent to the urothelium. In the rabbit urethra, the binding sites were confined mainly to the circular smooth muscle layer. Neither radioligand membrane binding studies nor autoradiography revealed any specific [3H]AVP binding sites in the human bladder. AVP contracted rabbit bladder and urethral preparations concentration dependently. The contractions were inhibited by the V1-receptor selective antagonist A16 in a noncompetitive manner. However, A16 had no effects on contractions elicited by electrical-field stimulation. In preparations of the human bladder and urethra, AVP in concentrations up to 10(-5) M did not have any contractile effects. These results suggest that in the rabbit and human lower urinary tract, AVP-LI is synthesized locally and/or extracted from the circulation. It is unlikely that AVP is directly involved in the neurotransmission in these tissues, although in the rabbit bladder and urethra a modulatory role cannot be excluded. PMID- 1928433 TI - Adrenal sympathetic nerve activity in response to hypothalamic injections of 2 deoxy-D-glucose. AB - Adrenal sympathetic nerve activity after microinfusion of 2-deoxy-D-glucose (2 DG) into various hypothalamic nuclei was investigated in anesthetized rats. Infusion of 2-DG into the ventrolateral portion of the lateral hypothalamic area (LHA) induced a large and long-lasting increase (greater than 60 min) in adrenal nerve activity. In contrast, infusion into the dorsal or medial portion of the LHA tended to produce a small decrease with a return to baseline within approximately 60 min after the end of the infusion. The direct administration of 2-DG into either the paraventricular nucleus or the dorsomedial hypothalamic nucleus produced a strong inhibition of adrenal nerve activity. Infusions into the ventromedial hypothalamic nucleus induced either a decrease of adrenal nerve activity or were without effect. These findings provide evidence that induction of glucoprivation in the hypothalamus with 2-DG can excite or inhibit adrenal nerve activity, depending on the hypothalamic region. These data also indicate that the ventrolateral portion of the LHA plays an important role in the regulation of adrenal catecholamine secretion in response to glucoprivic conditions in the central nervous system. PMID- 1928434 TI - Insulin sensitivity and liver insulin receptor structure in ducks from two genera. AB - Insulin sensitivity and liver insulin receptor structure were studied in 5-wk-old ducks from two genera (Muscovy and Pekin). In the fasting state, both duck types were equally resistant to exogenous insulin compared with chicken. Despite the low potency of duck insulin, the number of insulin receptors was lower in Muscovy duck and similar in Pekin duck and chicken liver membranes. After 125I-insulin cross-linking, the size of the alpha-subunit of the receptors from the three species was 135,000. Wheat germ agglutinin-purified receptors from the three species were contaminated by an active and unusual adenosinetriphosphatase (ATPase) contaminant (highest activity in Muscovy duck). Sequential purification of solubilized receptor from both duck types on lentil and then wheat germ agglutinin lectins led to a fraction of receptors very poor in ATPase activity that exhibited a beta-subunit size (95,000) and tyrosine kinase activity similar to those of ATPase-free chicken insulin receptors. Therefore the ducks from the two genera exhibit an alpha-beta-structure for liver insulin receptors and a clear difference in the number of liver insulin receptors. Their sensitivity to insulin is, however, similarly decreased compared with chicken. PMID- 1928435 TI - Influence of splenectomy on hemodynamics during cardiac tamponade. AB - The effect of prior splenectomy on the hemodynamics of cardiac tamponade was investigated in 15 closed-chest pentobarbital sodium-anesthetized dogs. Hemodynamics were compared at baseline and during staged cardiac tamponade (pericardial pressures of 5, 10, and 15 mmHg) at control (n = 15) and after splenectomy (n = 8) and sham operation (n = 7). The fall in mean arterial pressure with cardiac tamponade was significantly greater in splenectomized dogs than in either sham-operated or control dogs (P less than 0.001). Cardiac output was more depressed at the third level of cardiac tamponade in splenectomized than in sham-operated or control dogs (12.8 +/- 14.5 vs. 29.3 +/- 8.7 and 25.4 +/- 9.4 ml.min-1.kg-1, respectively; both P less than 0.05 vs. splenectomy). Hemodynamic failure, defined as an inability to maintain mean arterial pressure greater than 50 mmHg for 5 min, occurred at a lower pericardial pressure in splenectomized than in sham-operated dogs (13.1 +/- 3.8 vs. 18.1 +/- 3.5 mmHg, P less than 0.05). Hematocrit increased significantly with cardiac tamponade in controls and sham-operated but not splenectomized dogs. The percent increase in hematocrit from baseline to the third stage of cardiac tamponade was 19.6 +/- 9.8 and 22.3 +/- 5.6% in control and sham dogs, respectively. Thus the canine spleen plays an important role in cardiovascular compensation to cardiac tamponade. Parallel changes in hematocrit suggest that a part of this response is due to splenic autotransfusion. PMID- 1928436 TI - Zucker and Wistar diabetic fatty rats show different response to adrenalectomy. AB - The short-term effects of adrenalectomy on certain aspects of glucose homeostasis and adiposity were examined in Zucker and Wistar diabetic fatty (WDF) rats. Ten week-old male obese and lean WDF and Zucker rats were adrenalectomized or underwent sham operation. Obese rats of each strain were pair fed the intake of obese adrenalectomized rats. Intragastric glucose tolerance tests showed that sham-operated obese rats of both strains were severely hyperinsulinemic compared with leans; adrenalectomy and pair feeding reduced palsma insulin to lean levels in Zucker but not WDF rats. At the time they were killed, sham-operated obese WDF rats were significantly hyperglycemic and hyperinsulinemic compared with other groups, but adrenalectomy reduced plasma glucose and insulin to lean levels in both strains. Adrenalectomy reduced inguinal and retroperitoneal fat pad weights more in Zucker than WDF obese rats. Although adrenalectomy decreased epididymal and inguinal fat cell size in both obese rat strains, the effect was greater in Zucker compared with WDF rats. These data suggest that the basis for the differential response to adrenalectomy in obese WDF and Zucker rats may reside in their different genetic backgrounds. PMID- 1928437 TI - Ontogeny of canine intrathoracic cardiac nervous system. AB - The functional cardiac innervation of 61 puppies from nine different litters (2-8 littermates), ranging in age from 1 day to 7 wk, was investigated. The efferent sympathetic nervous system exerted minimal effects on the heart of 1-day-old puppies, gradually influencing the heart more thereafter such that by 7 wk of life it was functionally mature. In contrast, efferent parasympathetic cardiac innervation was well developed at birth, maturing thereafter such that by 4-7 wk of age its capacity to modulate the heart was similar to that found in adults. The right- and left-sided efferent sympathetic and parasympathetic intrathoracic nervous systems induced similar cardiac modulation throughout this period of development. Cardiac myocyte beta-adrenergic receptors were partially functional at birth, as determined by responses elicited by supramaximal doses of the beta agonist isoproterenol. Responses elicited by isoproterenol became greater over the following 7 wk of life, when they were found to be similar to those elicited in adults. By 1 wk of age, synaptic mechanisms in intrathoracic sympathetic ganglia involved in cardiac regulation were relatively well developed, with cardiopulmonary-cardiac reflexes present but not functionally mature at that age. It is concluded that maturation of the efferent sympathetic nervous system modulating the canine heart depends to a large extent on the ontogeny of cardiac beta-adrenergic receptors rather than the ontogeny of synapses in intrathoracic ganglia. Furthermore, even though functional cardiac efferent parasympathetic innervation is present before efferent sympathetic innervation, both reach maturity at about the same age. PMID- 1928438 TI - Regularly scheduled voluntary exercise synchronizes the mouse circadian clock. AB - Circadian rhythm entrainment has long been thought to depend exclusively on periodic cues in the external environment. However, evidence now suggests that appropriately timed vigorous activity may also phase shift the circadian clock. Previously it was not known whether levels of exercise/activity associated with spontaneous behavior provided sufficient feedback to phase shift or synchronize circadian rhythms. The present study investigated this issue by monitoring the sleep-wake, drinking, and wheel-running circadian rhythms of mice (Mus musculus) during unrestricted access to running wheels and when free wheel rotation was limited to either 12- or 6-h intervals with a fixed period of 24 h. Wheel rotation was controlled remotely. Mice spontaneously ran in wheels during scheduled access, and free-running sleep-wake and drinking circadian rhythms became entrained to scheduled exercise in 11 of 15 animals. However, steady-state entrainment was achieved only when exercise commenced several hours into the subjective night. The temporal placement of running during entrainment was related (r = 0.7003, P less than 0.02) to free-running period before entrainment. Mice with a free-running period less than 23.0 h did not entrain but exhibited relative coordination between free-running variables and the wheel availability schedule. Thus the circadian timekeeping system responds to temporal feedback arising from the timing of volitional exercise/activity, suggesting that the biological clock not only is responsive to periodic geophysical events in the external environment but also derives physiological feedback from the spontaneous activity behaviors of the organism. PMID- 1928439 TI - Peripheral vascular resistance and regional blood flows in hypertensive Dahl rats. AB - The aim of this study was to determine whether different organs undergo similar increases in vascular resistance with hypertension in the Dahl salt-sensitive rat. Cardiac output and organ blood flows were measured with microspheres in anesthetized salt-sensitive and salt-resistant rats fed a high- (7%) or normal- (0.45%) salt diet for 4 wk. High salt intake produced hypertension only in salt sensitive rats. Cardiac index for the hypertensive group was not different from that for any other group, whereas peripheral resistance index was elevated in proportion to arterial pressure. There were no differences among groups in the fraction of cardiac output supplying the myocardium, intestine, diaphragm, spinotrapezius muscle, or gracilis muscle. The fraction of cardiac output supplying the kidneys was lower in salt-sensitive rats (13%) than in salt resistant rats (17%) and, among salt-sensitive rats, lowest in the high-salt group. Therefore all the organs studied contribute to increased total peripheral resistance in the hypertensive Dahl rat, with the renal vasculature undergoing the largest resistance increase. Different muscles undergo similar increases in vascular resistance, despite differences in the microvascular abnormalities accompanying salt-induced hypertension. PMID- 1928440 TI - The interactive effects of dietary sodium chloride and calcium on cardiovascular stress responses. AB - Blood pressure increases associated with salt loading in the spontaneously hypertensive rat (SHR) are attenuated with increased dietary calcium. To assess the cardiovascular effects of these nutrients during stress, blood pressure and sympathoadrenal responses to stress were compared in salt-sensitive SHRs fed diets containing normal (0.73%) or high (8.0%) NaCl combined with either low (0.2%) or high (2.0%) calcium. NaCl-loaded rats showed increased blood pressure and exaggerated plasma epinephrine changes during restraint stress. Elevated blood pressure responses to exogenous NE were also observed with high salt intake. Supplementary calcium reduced blood pressure and attenuated the hypertensive effect of NaCl during restraint stress. Animals fed the high calcium diets had lower plasma epinephrine levels while vascular reactivity was not affected. The results indicate that increased sympathoadrenal activity and vascular reactivity contribute to elevated blood pressure and exaggerated pressor responses produced by NaCl loading in the salt-sensitive SHR. However, the hypotensive effects of dietary calcium appear to be related to sympathoadrenal activity but not vascular reactivity. PMID- 1928441 TI - Comparison of carotid baroreflex control of plasma AVP concentration in conscious and anesthetized dogs. AB - We compared carotid sinus baroreflex control of endogenous plasma arginine vasopressin (AVP) in chronically prepared conscious and acutely prepared anesthetized dogs. The carotid sinuses of both conscious and pentobarbital anesthetized dogs were isolated bilaterally and perfused at constant pressures. Carotid sinus pressure (CSP) was changed between 200 and 50 mmHg in 25-mmHg steps in intact conscious and anesthetized dogs. Similar runs were repeated after vagotomy. Mean arterial pressure (MAP) and heart rate (HR) were monitored. At each interval of CSP, blood was withdrawn for AVP analysis by radioimmunoassay. MAP responses to changes in CSP were not different in the four experimental groups. Both anesthesia and vagotomy increased the HR responses to changes in CSP. With vagi intact, AVP increased at high CSP in conscious but not in anesthetized dogs. After vagotomy, low CSP led to an increase in plasma AVP that did not differ between conscious and anesthetized dogs. The results suggest that the release of AVP is modulated by the action of the carotid baroreflex as a normal component of an integrated efferent response. The response is similar in conscious and pentobarbital-anesthetized dogs and is normally buffered by reflexes with vagal afferents. PMID- 1928442 TI - Vasopressin-induced bradycardia in barodenervated rats. AB - Experiments were performed on conscious chronically instrumented rats to determine the contribution of baroreceptor reflex (BRR)-independent mechanisms in the bradycardia associated with intravenous administration of arginine vasopressin (AVP). At least 2 wk prior to experimentation, the aortic and carotid baroreceptors were denervated in six rats. Following recovery, the maximum bradycardic responses to pressor doses of phenylephrine (PE) or AVP were determined on separate days in each animal. Pulse interval (PI) was calculated from heart rate (HR), and the slopes of PI vs. mean arterial blood pressure (MABP) and PI vs. dose were determined for each experiment by linear regression. There was no significant correlation of PI vs. MABP in response to bolus PE in these barodenervated rats. However, there was a significant correlation of PI vs. MABP and PI vs. dose in response to AVP in five of the six barodenervated rats. These data suggest that pressor levels of AVP may elicit bradycardia independent of the BRR. Another group of experiments was performed in the Langendorff isolated rat heart preparation to assess the direct chronotropic effect of AVP. Hearts were not paced, and the coronary arteries were perfused at a constant flow. HR was determined at various concentrations of AVP (n = 4 at each dose). In addition, because unpaced hearts exhibited low intrinsic rates, the same protocol was performed in hearts receiving isoproterenol to elevate basal HR (n = 4 at each AVP dose). There was no chronotropic effect of AVP in isolated hearts with or without isoproterenol administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928443 TI - Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole. AB - Underlying cellular hypoxia, which may be difficult to detect, has been postulated to be a major cause of morbidity and mortality in sepsis. We employed the novel hypoxic marker [18F]fluoromisonidazole to determine whether cellular hypoxia was present in a peritonitis model of sepsis in the rat. A second group of septic and control rats had organ blood flow measurements determined by the radiolabeled microsphere technique to relate possible ischemia to decreased organ perfusion. No evidence of cellular hypoxia was detected in skeletal muscle, brain, liver, heart, or diaphragm in the septic rats. Ligation of the femoral artery caused a greater reduction in flow (55% decrease vs. 20% decrease, P less than 0.05) and an increased retention of [18F]fluoromisonidazole in skeletal muscle of the septic rats. We conclude that sepsis does not invariably result in systemic, i.e., multiorgan, cellular hypoxia and that underlying cellular hypoxia is not the major pathophysiological abnormality in sepsis. The greater reduction in muscle blood flow and the increased retention of [18F]fluoromisonidazole in the ischemic muscle of septic rats implies that they may be more vulnerable to hypoxia. PMID- 1928444 TI - Olfactory bulbectomy lengthens circadian period of locomotor activity in golden hamsters. AB - Removal of the olfactory bulbs (BX) of rats or mice lengthens the circadian period of locomotor activity. In golden hamsters, BX elevates serum gonadotropin levels of hamsters maintained in long or short photoperiod and prevents the testicular regression associated with short days without altering the secretion or action of pineal melatonin. The present study examined the influence of BX on circadian wheel-running activity in hamsters and tested whether this effect was related to changes in serum testosterone levels. BX lengthened the free-running period of locomotor activity in gonadally intact hamsters by a mean of 21.0 min, and BX had a similar effect in orchidectomized animals with or without testosterone replacement. These results suggest that the olfactory bulbs normally tend to increase the frequency of the hamster's circadian oscillator and that this effect is unrelated to altering gonadal steroid levels. PMID- 1928445 TI - Hypertrophy of stellate ganglion cells in hypertensive, but not hyperactive, rats. AB - The dendritic complexity of peripheral autonomic neurons is positively matched with the size of the target they innervate, apparently by trophic interactions with the target (D. Purves, W. D. Snider, and J. T. Voyvodic. Nature Lond. 336: 123-128, 1988). We have asked whether the vascular hypertrophy associated with hypertension is accompanied by dendritic hypertrophy of sympathetic ganglion cells. To do this, we examined the morphology of stellate ganglion cells in the spontaneously hypertensive rat (SHR), its normotensive control Wistar-Kyoto rat (WKY), and two new strains derived from the SHR that independently express the hypertensive phenotype of the SHR (WKHT) and the behavioral hyperactivity present in the SHR (WKHA). Cells were examined by intracellular staining with horseradish peroxidase in in vitro preparations of the ganglia. Carotid arterial wall size was also examined. Significant hypertrophy of both the carotid arterial wall and stellate ganglion cell dendrites was observed in the two hypertensive strains (SHR and WKHT) but not in either of the normotensive strains (WKY and WKHA). This increased total dendritic length of stellate ganglion cells associated with hypertension provides a greater target area for preganglionic innervation that may result in hyperinnervation of these cells. PMID- 1928446 TI - Differentiation of two cardiovascular regions within caudal ventrolateral medulla. AB - The caudal ventrolateral medulla (CVLM) plays a significant role in the regulation of sympathetic nerve activity (SNA) and arterial pressure; however, the use of lesions to examine its role in mediating baroreceptor reflex control of SNA has yielded discrepant results. We hypothesize that this may have arisen from anatomic segregation of neurons within the CVLM that subserve different functions in sympathetic control. Thus we used microinjections of the excitotoxic agent kainic acid (200 pmol in 20 nl) to determine the effects of inactivation of neuronal cell bodies in a rostral and a caudal subregion of the CVLM on SNA, arterial pressure, and baroreceptor reflex function in urethan-anesthetized rats. Interruption of neuronal activity in the rostral CVLM (sites from 0.6 mm caudal to 0.5 mm rostral to the rostral border of the lateral reticular nucleus) elevated SNA (post-kainic acid 214% of control) and arterial pressure (+34 mmHg) and eliminated the inhibition of splanchnic SNA evoked by either aortic nerve stimulation or the pressor response to intravenous norepinephrine. In addition, the cardiac-related component of spontaneous SNA was abolished as judged from post-R wave averages and from power spectral analysis. In contrast, although a similar disruption of neuronal activity in the caudal CVLM (sites 0.0-0.6 mm rostral to the caudal border of the lateral reticular nucleus) produced a comparable increase in spontaneous SNA (post-kainic acid 196% of control) and arterial pressure (+20 mmHg), it was without effect on the ability of the baroreceptor reflex to inhibit SNA, and it enhanced the synchronization of the spontaneous bursts in SNA to the cardiac cycle. Our results suggest an organization of the CVLM in which neurons in its rostral portion are required for an effective baroreceptor reflex, whereas those in the caudal CVLM serve to limit SNA and blood pressure independent of the baroreceptor reflex. PMID- 1928447 TI - Corticotropin-releasing factor in the ovine fetus and pregnant ewe: role of placenta. AB - In the sheep, maternal plasma adrenocorticotropic hormone and cortisol are increased in late pregnancy, and fetal plasma cortisol and adrenocorticotropic hormone rise precipitously in late gestation. To test whether the ovine placenta secretes corticotropin-releasing factor (CRF) into either the maternal or fetal circulation, pregnant ewes and their fetuses were prepared with femoral arterial catheters and uterine and umbilical venous catheters. Samples were taken from all sites before and during hypoxia. There was no difference in CRF concentration across the placenta in the mothers or the fetuses under resting or hypoxemic conditions, but maternal and fetal arterial plasma CRF concentrations increased between 128 and 145 days. In a second study, maternal and fetal femoral venous plasma CRF concentrations were measured 1-19 days before spontaneous parturition. The mean concentration increased 8.6 +/- 0.6 pg/ml 11-19 days before parturition to 13.0 +/- 1.0 and 13.2 +/- 1.4 pg/ml in fetuses 4-8 and 1-3 days before parturition, respectively. Maternal plasma concentrations did not significantly increase in the days closer to parturition. These studies demonstrate that there are low but measurable CRF concentrations in fetal and maternal sheep plasma but that these are not the result of tonic placental secretion of CRF. PMID- 1928448 TI - Regulation of ATP-dependent surfactant secretion and activation of second messenger systems in alveolar type II cells. AB - Several different classes of agonists are known to stimulate exocytosis in type II cells. These agonists cause increases in second messengers, such as adenosine 3',5'-cyclic monophosphate (cAMP) or cytosolic Ca2+, and/or stimulate protein kinase C. We studied generation of cAMP and phosphoinositide (PI) turnover in monolayer cultures of type II cells and measured [Ca2+]i in single cultured cells. ATP [10(-4) M], which stimulates secretion of phosphatidylcholine (PC) and increases cellular cAMP, also stimulated PI turnover and increased [Ca2+]i. 12-O tetradecanoylphorbol-13-acetate (TPA), which stimulates PC secretion and activates protein kinase C, did not increase [Ca2+]i. Pretreatment of type II cells with the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1 naphthalenesulfonamide (W-7) inhibited the PC secretion induced by ATP and TPA and blocked the increase in PI turnover caused by ATP. ATP-dependent surfactant secretion and stimulation of PI turnover could also be inhibited by pretreatment of the cells with pertussis toxin. We used the fluorescent probe indo-1 to measure [Ca2+]i in single cultured type II cells. ATP produced rapid transient increases in [Ca2+]i, which could be prevented by pretreatment of the cells with either TPA or W-7. Our data suggest that pertussis toxin-sensitive G protein(s) are involved in ATP-dependent activation of PI turnover and in secretion of surfactant in type II cells. Activation of protein kinase C blocks the ATP stimulated increase in [Ca2+]i. Finally, calmodulin may be involved in the regulation of ATP-dependent increase in [Ca2+]i, the activation of PI turnover, and the secretion of surfactant in type II cells. PMID- 1928449 TI - Type II pneumocyte proliferation in vitro: problems and future directions. AB - In adult animals, the type II pneumocyte is progenitor of both the type I and type II alveolar epithelium. In primary culture, however, the fate of this cell is uncertain. Type II cells in culture lose their differentiated properties and eventually resemble type I cells, but a lack of specific markers has complicated the characterization of the phenotype acquired in vitro. Furthermore, limited proliferation of these cells in vitro has precluded definition of the relationship between type II cell proliferation and differentiation. Recent work in this laboratory has involved the correlation of flow cytometric cell cycle analysis with phenotype markers. Initial results indicate that isolation of type II cells induces cell cycle block similar to that sustained by other cell types in response to stress. In addition, preliminary evaluation of phenotype suggests that traditional markers become ambiguous beyond the 1st day of primary culture. These results raise concern related to the interpretation of experiments conducted in vitro. This report discusses the implications of these findings and directions for future work. PMID- 1928450 TI - Time course of mechanical efficiency during afterloaded contractions in isolated cardiac muscle. AB - The time course of mechanical efficiency during working contractions in rabbit papillary muscle is presented. Efficiency is found to remain relatively constant during the working portion of the twitch, when the muscle is contracting against a constant load. As afterload was decreased, efficiency increased to 65 +/- 11% (mean +/- SE, n = 3) at 10% developed force at maximum length. This is in contrast to muscle work, which reached a peak of 3.0 +/- 0.3 (n = 6) mJ/g at 50% developed force at maximum length. PMID- 1928451 TI - Phosphocreatine pathway for energy transport: ADP diffusion and cardiomyopathy. AB - Chemically skinned (by treatment with saponin, 40 micrograms/ml) isolated cardiomyocytes were used to study the intracellular diffusion of ADP and creatine (Cr). Stimulation of respiration was studied in these cardiomyocytes without intact sarcolemma and in isolated heart mitochondrial by addition of ADP and Cr in the presence of 0.2 mM ATP (via mitochondrial creatine kinase reaction: Cr + MgATP = MgADP + PCr). The Michaelis constant (Km) for Cr was similar in both cases, 5.67 +/- 0.11 (SD) mM in skinned myocytes and 6.9 +/- 0.2 mM in mitochondria, showing that there is no significant restriction to the diffusion of this substrate. However, the apparent Km for external ADP increased from 17.6 +/- 1.0 microM for mitochondria to 250 +/- 38 microM for skinned cardiomyocytes, showing decreased diffusivity of ADP as a result of binding to cellular structures. In the presence of 25 mM Cr, the Km for ADP for myocytes decreased to 35.6 +/- 5.6 microM due to the coupling of the creatine kinase and oxidative phosphorylation reactions. Provision of substrate for the creatine kinase reaction amplified the weak ADP signal in the regulation of respiration. The activity of the mitochondrial creatine kinase was decreased by a factor of two in cardiomyopathic hamsters and human hearts and was associated with a twofold decrease in creatine-stimulated respiration. These data show a potentially key role of mitochondrial creatine kinase in the regulation of cellular respiration and the possible importance of changes in its activity for the functional disturbances of the cardiomyopathic heart. PMID- 1928452 TI - Energy-linked functional alterations in experimental cardiomyopathies. AB - Changes in high-energy phosphate content and cardiac contractile function of isolated rat hearts as well as changes in Ca2+ sensitivity and mitochondrial respiration of myocardial skinned fibers were assessed in hereditary cardiomyopathies and in cardiomyopathies induced by chronic treatment with adriamycin or norepinephrine, by autoimmunization, by diabetes, or by creatine deficiency. The sum of ATP and phosphocreatine contents as well as cardiac output at standard load conditions was substantially lower in almost all groups. The common features of cardiac pump failure were mild bradycardia, elevated left ventricular (LV) diastolic pressure, and stiffness that limited cardiac contractile adaptation to volume or resistance loads. The LV diastolic stiffness at maximal functional load was inversely correlated with high-energy phosphate content. Increased myofibrillar sensitivity to Ca2+ and defective function of mitochondrial creatine kinase were found in skinned myocardial fibers. These results suggested that both increased myofibrillar Ca2+ sensitivity and energy deficiency within myofibrils may contribute to increased myocardial stiffness. Increased stiffness limits LV filling but facilitates pressure development, which partly compensates for decreased contractility of cardiomyopathic hearts. PMID- 1928453 TI - Control of cardiac energy turnover by cytoplasmic phosphates: 31P-NMR study. AB - Energy flux, estimated from the cardiac work index (pressure-rate product) and the rate of oxygen consumption, was varied in different ways; and the free concentrations of cytosolic phosphates were detected by the 31P-nuclear magnetic resonance method. A reversible decrease in phosphocreatine (PCr) and concomitant increase in [ADP] at nearly constant Pi were induced by 2-deoxyglucose (2-DG) treatment and its subsequent washout and were followed by a reversible suppression of pressure-rate product and elevation of end-diastolic pressure. 2 DG treatment also resulted in an irreversible and severe reduction of the cytosolic adenine nucleotide pool (to approximately one-third of control value) that did not recover during 2-DG washout. Reduction of the energy turnover rate, either by suppression of the PCr shuttle with iodoacetamide or by inhibition of the respiratory chain with amytal, was associated with a drop of PCr level, an elevation of both [ADP] and [Pi], and a rise of end-diastolic pressure. In contrast, a decrease in energy flux by reduction of perfusate Ca2+ led to a PCr rise and a fall in [ADP] and [Pi]. Most of these experimental groups were exposed to two types of loads, isoproterenol stimulation and coronary flow (CF) elevation. Iodoacetamide-treated hearts showed a poor mechanical response to both types of loads compared with other groups. The metabolic response to isoproterenol was uniform in all groups and was associated with some decrease in PCr and increase of [ADP] and [Pi], implying limitations in the respiratory chain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928454 TI - Effect of work on intracellular calcium of the intact heart. AB - Intracellular calcium has been proposed to play a key role in the orchestration of metabolic rate with contractile activity in the mammalian heart. Calcium is believed to accomplish this task by modulating the contractile apparatus as well as the metabolic process directly, and perhaps simultaneously, during alterations in cardiac work. The purpose of this study was to evaluate whether appropriate changes in intracellular calcium accompany alterations in cardiac work in the intact working rabbit heart. A range of myocardial oxygen consumption was obtained from 0.94 to 6.51 mumol.g LV wt-1.min-1 by changing afterload or beta agonist addition. With the increase in work and associated increase in respiration, an increase in intracellular calcium was observed, on the basis of indo-1 fluorescence. These results indicate that intracellular calcium is a valid candidate as a cytosolic transducer contributing to the orchestration of myofibril adenosinetriphosphatase activity and oxidative phosphorylation in the intact heart. PMID- 1928455 TI - Targeting of macromolecular carriers and liposomes by antibodies to myosin heavy chain. AB - Macromolecular carriers and liposomes were covalently coupled to monoclonal antibodies against cardiac myosin heavy chain. Deferoxamine-modified polymers bound tightly with 67Ga and 68Ga radioisotopes. Ternary deferoxamine-polylysine antibody conjugates specifically targeted the radioisotopes to a myosin-coated microplate. Scatchard analysis revealed a high affinity of the conjugate for the target with a Kas of approximately 10(8) M-1. Liposomes that contained immobilized antimyosin antibodies were targeted specifically to the myosin-coated plate. Additional coating of these liposomes with polyethylene glycol reduced specific binding to the target in vitro. However, because of the presence of polyethylene glycol on the surface of liposomes, these liposomes had a long half life and slowly cleared from the blood-stream after intravenous injection. These immunoliposomes showed up to 16- to 18-fold specific localization to the necrotic areas of the myocardium in rabbits with experimental infarction. PMID- 1928456 TI - Phenotypic changes of human aortic smooth muscle cells during development and in the adult vessel. AB - To characterize phenotypic expression of human aortic smooth muscle cells (SMCs), we have studied the content of cytodifferentiation-related cytoskeletal proteins, and of fibronectin (FN) variants in the samples of media from the fetal, child, and adult aorta and in the subendothelial intima of the normal and atherosclerotic aorta. Mature SMCs from the adult aortic media contained high amounts of alpha-SM-actin, SM-myosin heavy chains, meta-vinculin, and 150 kDa caldesmon. Cytokeratin 8 and extra domain-containing variants of FN (A-FN and B FN) were not found in these cells. The SMCs from the aortic media of 10-wk-old fetus contained low amounts of the SM markers, expressed cytokeratin 8, A-FN, and B-FN. In 25-wk-old fetus, as well as in 2- and 6-mo-old child, aortic medial SMCs expressed an intermediate phenotype, and only in 18-mo-old child were the cells found to be similar to those from adult media. SMCs from the normal adult subendothelial intima contained reduced amounts of meta-vinculin and of 150 kDa caldesmon, and they expressed A-FN. In addition, the SMCs from atherosclerotic fibrous plaque contained a decreased proportion of alpha-SM-actin and of SM myosin heavy chains, whereas cytokeratin 8 was found. Therefore we conclude that the SMCs from intimal thickenings appear to express a less mature phenotype than that of the medial cells from adult aorta. Rather, these SMCs contain reduced amounts of the SM markers and express proteins typical of the fetal SMC phenotype, A-FN and cytokeratin 8. PMID- 1928457 TI - Impact for molecular biology in cardiology. AB - The recent development and application of the techniques of recombinant DNA and molecular biology ignited an explosion in biomedical research, which has been embraced by medicine. However, cardiology as a subspecialty has been slower in adopting these techniques, in part because the heart is a nonproliferating organ and in part because it was not easily accessible until recently. The techniques of recombinant DNA were not possible until the 1970s. In that decade four major discoveries occurred that launched molecular biology into the 21st century. These seminal contributions were 1) the discovery and application of specific restriction endonucleases, 2) the discovery of reverse transcriptase, 3) the development of the cloning technique, and 4) the ability to rapidly sequence nucleic acids. The techniques of recombinant DNA offer several unique advantages over existing scientific disciplines, such as the abilities: 1) to perform in vivo structure-function analysis, 2) to genetically engineer drugs, 3) to perform diagnostic in situ hybridization, 4) to isolate genes responsible for hereditary disorders, and 5) to understand the genetic regulation of cardiac growth. These techniques are discussed in their application to cardiac disorders, including the development of new recombinant molecules for the treatment of coronary thrombosis and the potential to modulate the cardiac growth response to various forms of injury such as myocardial infarction and hypertension. PMID- 1928458 TI - Specific proteins synthesized in human lymphocytes during hypoxia. AB - Hypoxia is a severe stress factor to which man and most other mammalian species are capable of adapting. However, the cellular mechanisms that enable cells to tolerate decreases in ambient oxygen tension are still unknown. We have previously shown that hypoxia induces the synthesis of unique proteins (molecular mass 38, 52, 74, 76 kDa) in human aortic endothelial cells and lymphocytes. In this study we investigated the specificity of hypoxia on the upregulation of these hypoxic stress proteins (HYP) in human peripheral blood lymphocytes and the role of calcium in this response. 35S-methionine pulse-labeling studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two-dimensional electrophoresis and autoradiography demonstrated that normobaric hypoxia (4% O2 5% CO2-91% N2) enhanced synthesis of HYP, whereas heat-shock protein synthesis was not affected. Heat shock (42 degrees C) and cold stress (4 degrees C) did, however, induce synthesis of heat-shock protein but not HYP. The 38-kDa HYP is the major protein for which synthesis is upregulated by hypoxia. Its isoelectric point (pI) is 3.5-4.0, and it is localized in the cytosol. The 52-kDa HYP has a pI of greater than 6.5, and it is also localized in the cytosol. The 74- and 76 kDa HYPs appear to be membrane bound. In addition to hypoxia, an increase in calcium concentration in the culture media (25-50 mM) enhanced synthesis of HYP. An ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)/Ca2+ binding complex, when added to blood lymphocytes during exposure to hypoxia, significantly inhibited HYP synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928460 TI - Subspecialization in psychiatry. PMID- 1928459 TI - Cellular adaptation during chronic neonatal hypoxic pulmonary hypertension. AB - Newborn animals develop more severe hypoxic pulmonary hypertension than do adults, their vascular changes are greater, and both the hypertension and vascular changes occur more rapidly. We hypothesize that this differential developmentally controlled response may arise from either a difference in the type or quantity of endogenously secreted mediators in response to a given injury or a difference in the replicative and/or matrix-producing response of the vascular cells to physical or chemical stimuli. We investigated the effect of chronic hypoxia (14 days) on the proliferative and matrix-producing phenotype of the neonatal (14-day-old) pulmonary artery smooth muscle cell (SMC) and examined the heterogeneity and potential mechanisms responsible for this response. In situ hybridization studies demonstrated a remarkable change in the distribution of cells hybridizing with a tropoelastin cRNA probe after 14 days of hypoxia. Studies also demonstrated a population of SMC that did not hybridize with the elastin or collagen probes, indicating that the pulmonary artery contains SMC of multiple phenotypes and that the response to hypoxic and hemodynamic stress is not uniform for the various types. Bromodeoxyuridine labeling experiments indicated a large increase in DNA synthesis in hypertensive vessels, which, again, was not uniform either across or along the arterial wall. In vitro experiments with neonatal SMC suggested that hypoxia alone could not be responsible for the proliferative or matrix changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928461 TI - Is the poor sleep of shift workers a disorder? AB - OBJECTIVE: The purpose of this article is to describe the impact of shift work on sleep, as recently acknowledged in official nosologies of sleep disorders, and to discuss whether sleep altered by shift work actually constitutes a disorder. METHOD: The authors review subjective responses to recent survey questions about sleep and polygraphic measurements of sleep in shift workers and describe sleep clinic experiences with complaints related to shift work. FINDINGS: Shift work entails wide variation in work schedules, sleep quality, and worker tolerance and a high prevalence of night-shift sleepiness. It probably affects rates of drug use, health status, and family organization. Clinical presentations were rare, highly varied, and empirically treated. The United States, unlike other countries, has no legal restrictions on shift work. CONCLUSIONS: As a clinical phenomenon, sleep altered by shift work is common and varied, probably expresses nonphysiological sleep-wake scheduling, and is little treated. Further study of its health effects and consideration of whether it is a "disorder" or a "problem" seem warranted. PMID- 1928462 TI - Somatization and psychiatric disorder in the NIMH Epidemiologic Catchment Area study. AB - OBJECTIVE: Somatization has often been viewed as a defense against awareness of emotional distress or as a masked version of depression. This report examines whether community residents with high levels of functional somatic symptoms also report overt psychological distress and whether somatization is associated with any specific psychiatric disorder. METHOD: Analyses used data from the community sample of the National Institute of Mental Health Epidemiologic Catchment Area (ECA) study, a population-based survey of psychiatric morbidity among more than 18,000 residents of five U.S. communities. RESULTS: Increasing number of somatization symptoms was strongly associated with overt expression of psychological distress and psychiatric symptoms. Among ECA respondents with five or more current functional somatic symptoms, 63% reported current psychological symptoms and 50% met criteria for a current psychiatric diagnosis (compared to 7% and 6%, respectively, among those with no current somatization symptoms). Somatization symptoms showed strongest associations with anxiety and depressive symptoms, intermediate association with symptoms of psychotic disorders, and weakest associations with symptoms of substance abuse and antisocial personality. CONCLUSIONS: ECA study respondents with high levels of somatization symptoms typically reported overt psychological distress, especially anxiety and depression. Patterns of response do not support a dissociation between physical and emotional symptoms. Functional somatic symptoms appear to be common expressions of distress instead of defenses against awareness. PMID- 1928463 TI - The family history method: whose psychiatric history is measured? AB - OBJECTIVE: The family history method, in which an informant is asked about the history of psychiatric illness in relatives, is widely used in psychiatric research. Previous research has examined the influence on family history information of characteristics of the relative. In this report, the authors seek to clarify the impact on family history reporting of the psychiatric history of the informant. METHOD: Both members of female twin pairs from a population-based twin registry were asked about the history of major depression, generalized anxiety disorder, and alcoholism in their mother and father. The authors examined twin pairs discordant for each of the three diagnoses and predicted that the affected twin would report higher rates of the same disorder in her parent than would the unaffected twin. RESULTS: Twins with a history of major depression or generalized anxiety disorder but not twins with alcoholism were significantly more likely to report the same disorder in their parents than were their unaffected co-twins. CONCLUSIONS: For major depression and generalized anxiety disorder, a family history diagnosis appears to reflect the psychiatric history of both the relative and the informant. Caution may be needed in the interpretation of results based on the family history method, although the magnitude of this problem may be attenuated by the use of multiple informants. PMID- 1928464 TI - Mood variability: a study of four groups. AB - OBJECTIVE: The authors' goal was to determine whether self-rated patterns of mood regulation differed among patients with major depression, patients with borderline personality disorder, patients with premenstrual syndrome (PMS), and normal subjects. METHOD: Fourteen days of morning and evening mood self-ratings on a visual analog scale were analyzed for 65 female subjects (10 with major depression, 16 with borderline personality disorder, 15 with PMS, and 24 without psychiatric diagnoses). For each individual, the mean and standard deviation of morning and evening ratings, the mean absolute change in mood from one day to the next, and the change from morning to evening were determined. RESULTS: The four groups differed significantly on every measure of mood and mood variability except diurnal variation. As expected, the group with major depression had the lowest global ratings and a low degree of variability. The group with borderline personality disorder was less depressed than the group with major depression and showed a high degree of mood variability. Autocorrelation analysis suggested that mood ratings in borderline personality disorder vary randomly from one day to the next. The mood variability over the 14 days of the patients with PMS was significantly greater than that of normal subjects. CONCLUSIONS: The visual analog scale can capture patterns of mood and mood variability thought to be typical of these diagnostic groups. Mood disorders differ not only in the degree of abnormal mood but also in the pattern of mood variability, suggesting that mechanisms regulating mood stability may differ from those regulating overall mood state. PMID- 1928465 TI - Follow-up and family study of anxious depression. AB - OBJECTIVE: The failure of the concept of anxious depression to find its way into DSM-III-R led the authors to conclude that a further report on the occurrence of anxiety symptoms in depressed subjects is indicated. METHOD: The subjects were 327 consecutively evaluated inpatients and outpatients with primary unipolar depressive disorder at five university medical centers participating in the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression--Clinical Studies. The authors restricted their sample selection to patients with primary depressive disorder so that patients with other preexisting psychiatric disorders, especially anxiety disorders, would not contaminate the symptom picture, family studies, or follow-up. The examined six anxiety symptoms and derived a new anxiety summary score to show the effect of anxiety in depression on family data and 5-year outcome. RESULTS: Depressed subjects with higher ratings for anxiety took longer to recover. There was also a significant relationship between anxiety in depressed probands and the risk for primary unipolar depressive disorder, but not anxiety disorders or alcoholism, among 832 blindly interviewed first-degree relatives. CONCLUSIONS: These data confirm the usefulness of subdividing depressed patients according to anxiety symptoms: psychic and somatic symptoms of anxiety, taken together, significantly predict family illness and course. The data also emphasize the wisdom of requiring that generalized anxiety disorder not be diagnosed in the presence of a mood disorder. Clearly, symptoms of anxiety coexist with depression and need to be recognized for the effective treatment of the underlying depressive disorder. PMID- 1928466 TI - Serotonin function and depression: neuroendocrine and mood responses to intravenous L-tryptophan in depressed patients and healthy comparison subjects. AB - OBJECTIVE: This study was designed to compare central serotonergic function in depressed patients and healthy comparison subjects by examining neuroendocrine and mood responses to intravenous L-tryptophan. METHOD: One hundred twenty-six drug-free patients with DSM-III-R major depression (109 unipolar, 17 bipolar; 68 melancholic, 58 nonmelancholic; 28 psychotic, and 98 nonpsychotic patients) and 58 healthy comparison subjects participated. After an overnight fast, subjects received an intravenous infusion of L-tryptophan, 7 g. Blood was obtained for determination of serum prolactin, serum growth hormone (GH), and plasma tryptophan levels. Visual analogue scales were used to assess mood. RESULTS: Prolactin responses were blunted in nonmelancholic and higher in melancholic and psychotic depressed patients, while GH responses were blunted in combined unipolar, nonmelancholic, and nonpsychotic depressed patients. Controlling for baseline biological, clinical, and demographic factors eliminated the higher prolactin response in the melancholic and psychotic patients, attenuated the blunted GH response in the unipolar patients, and revealed a blunted GH response in the melancholic patients. Patients and comparison subjects differed on five of 13 mood responses, primarily because of baseline differences. CONCLUSIONS: These findings are consistent with previous studies demonstrating blunted neuroendocrine responses to intravenous L-tryptophan in depression. Restriction of these findings to specific subtypes of depression may reflect a differential role of serotonergic abnormalities in these subtypes. PMID- 1928467 TI - Low electrooculographic ratios in patients with seasonal affective disorder. AB - OBJECTIVE: Changes in retinal sensitivity to light have been hypothesized as etiological in seasonal affective disorder. This study was undertaken to investigate sensitivity to light in seasonal affective disorder using electrooculography (EOG), an objective measure of retinal light response. METHOD: In a mood disorders clinic, 19 depressed, drug-free patients with seasonal affective disorder, diagnosed by DSM-III-R criteria, were compared with 19 age- and sex-matched normal comparison subjects. All subjects had identical EOG testing performed during the winter. EOG (Arden) ratios were calculated from the EOG data. RESULTS According to multivariate analysis of variance, the EOG ratios in the patients with seasonal affective disorder were significantly lower than those of the normal comparison subjects, although there was considerable overlap in EOG ratios between patients and comparison subjects. CONCLUSIONS: These results suggest that seasonal affective disorder is associated with subtle retinal abnormalities at the level of the photoreceptor/retinal pigment epithelium complex, consistent with subsensitivity to light. A limitation of this study is that the retinal origins of the EOG response are nonspecific and still not completely elucidated. PMID- 1928468 TI - REM latency and the recovery from depression: getting over divorce. AB - OBJECTIVE: The authors' goal was to address five questions: 1) What is the frequency of early REM sleep in subjects in the process of divorce who meet diagnostic criteria for major depressive disorder? 2) What is the frequency of this sign in subjects in the process of divorce who are not depressed? 3) How often does this sign persist following remission of depressive symptoms? 4) What is the predictive value of early REM sleep among depressed subjects for later adjustment to the process of divorce? and 5) What is the role of a family history of depression or alcoholism in the presence and persistence of early REM sleep? METHOD: Two hundred fourteen volunteers undergoing marital separation were recruited; 70 of these subjects were selected for a 3-night sleep study. Forty of the 70 subjects met criteria for depression and 30 did not; 61 (87%) returned for repeat studies 1 year later. RESULTS: Fifteen (38%) of the 40 depressed subjects had short REM latency. Seven of these continued to have short REM latency 1 year later, but none of these met the criteria for depression at that time. A higher proportion of these subjects had made a good adjustment to their new life than did depressed subjects whose initial and follow-up REM latencies fell within the normal range. CONCLUSIONS: These data suggest that depressed individuals with normal REM latency may need more aggressive treatment intervention. PMID- 1928469 TI - Depression in recently bereaved prepubertal children. AB - OBJECTIVE: The purpose of this study was to ascertain depressive symptoms in recently bereaved prepubertal children and compare these symptoms with those of depressed prepubertal children. METHOD: The subjects were 38 children who had recently experienced the death of one but not both of their parents. They had to meet strict inclusion criteria so that the effects of bereavement per se, rather than other significant stressors, could be assessed. The comparison group consisted of 38 hospitalized, depressed children individually matched to each bereaved subject for age, sex, and socioeconomic status. All of the children underwent systematic and comprehensive evaluation. They and their parents were independently evaluated by trained interviewers using the parent and child versions of the Diagnostic Interview for Children and Adolescents. Family histories and basic demographic information were also obtained. RESULTS: The recently bereaved children endorsed many depressive symptoms. Thirty-seven percent of them met the DSM-III-R criteria for a major depressive episode. The depressed children, however, had more depressive symptoms on average than the bereaved children. The factors associated with increased depressive symptoms in the bereaved children were 1) the mother as the surviving parent, 2) preexisting untreated psychiatric disorder in the child, 3) family history of depression, and 4) high socioeconomic status. CONCLUSIONS: A considerable number of the bereaved children developed the clinical symptoms of a major depressive episode immediately after the death of a parent. The relation of these symptoms to the subsequent course of grief and to major depressive disorder remains unknown and should be studied further. PMID- 1928470 TI - A prospective follow-up study of so-called borderline children. AB - OBJECTIVE: The purpose of this study was to ascertain the current diagnosis in late adolescence or early adulthood of children who had previously been diagnosed as "borderline." METHOD: This was a prospective follow-up study of 19 of a group of 32 children (ages 6-10) who had been diagnosed as "borderline" during their treatment at the Massachusetts Mental Health Center approximately 10-20 years earlier. Life history information was collected, and axis I and axis II diagnoses were assigned by use of the Structured Clinical Interview for DSM-III-R and unstructured clinical interviews. RESULTS: The most significant finding was that, contrary to expectations, there were no axis I diagnoses of affective disorders or schizophrenia. On the other hand, axis II diagnoses were prevalent, and the overall outcome for the subjects was poor. Family stability was the only significant predictor of the relatively good outcome of five of the subjects. CONCLUSIONS: The childhood borderline diagnosis appears to be an antecedent of an array of adult personality disorders, but it is not associated with the adult borderline personality disorder per se, nor with axis I diagnoses. PMID- 1928471 TI - Trauma experiences, posttraumatic stress, dissociation, and depression in Cambodian refugees. AB - OBJECTIVE: The authors' goal was to determine the levels of trauma and psychiatric symptoms in a randomly selected group of Cambodian refugees and to determine the relationship between the amount of trauma experienced and subsequent psychiatric symptoms. METHOD: Data on traumatic experiences and symptoms of posttraumatic stress, dissociation, depression, and anxiety were collected on 50 randomly selected Cambodian refugees who had resettled in the United States. RESULTS: Subjects experienced multiple and severe traumas and showed high levels of all symptoms measured. Forty-three (86%) of the subjects met DSM-III-R criteria for posttraumatic stress disorder, 48 (96%) had high dissociation scores, and 40 (80%) could be classified as suffering from clinical depression. Correlations between trauma scores and symptom scores and among symptom scores were moderate to large. CONCLUSIONS: These results indicate that a high proportion of Cambodian refugees who are not psychiatric patients suffer from severe psychiatric symptoms and that there is a relationship between the amount of trauma they experienced and the severity of these symptoms. PMID- 1928472 TI - Symptoms of eating disorders in patients with obsessive-compulsive disorder. AB - OBJECTIVE: This study was designed to explore potential overlap of the symptoms of obsessive-compulsive disorder and eating disorders. METHOD: The authors administered a structured, self-rating scale, the Eating Disorder Inventory, to 59 outpatients at an obsessive-compulsive disorder clinic and to 60 sex-matched normal volunteers. The Eating Disorder Inventory has been previously validated as a reliable measure of the specific cognitive and behavioral dimensions of the psychopathology typical of patients with eating disorders. The scores of the patients with obsessive-compulsive disorder and of the healthy comparison subjects were compared with those of 32 female inpatients with anorexia nervosa (N = 10) or bulimia nervosa (N = 22) who had also been given the inventory. RESULTS: The patients with obsessive-compulsive disorder scored significantly higher than the healthy comparison subjects on all eight subscales of the Eating Disorder Inventory: drive for thinness, bulimia, body dissatisfaction, ineffectiveness, perfectionism, interpersonal distrust, interoceptive awareness, and maturity fears. Relative to the healthy subjects, male patients with obsessive-compulsive disorder had more symptoms than female patients with obsessive-compulsive disorder. The scores of the female patients with obsessive compulsive disorder were midway between those of the 32 female patients with eating disorders and those of the 35 female normal subjects. CONCLUSIONS: These results suggest that patients with obsessive-compulsive disorder display significantly more disturbed eating attitudes and behavior than healthy comparison subjects and that they share some of the psychopathological eating attitudes and behavior that are common to patients with eating disorders. PMID- 1928473 TI - Emergency psychiatric assessment of violence. AB - OBJECTIVE: The purpose of the study was to 1) ascertain whether there are clinical and demographic characteristics that distinguish dangerous from nondangerous patients evaluated in a psychiatric emergency service and 2) identify variables that distinguish dangerous patients who are hospitalized form those who are not. METHOD: The authors conducted a case comparison study of 99 psychiatric emergency patients whom staff identified as dangerous to others, that is, violent or potentially violent. Clinical staff were interviewed and records reviewed. These data were contrasted with record review data for 95 nondangerous patients. RESULTS: Log linear analysis showed that 1) variables relating to violence in community samples--age, sex, and past history of violence--related minimally or not at all to violence in this sample and 2) disposition to hospital versus community was associated with psychotic mental status and restraint in the psychiatric emergency service. Patients requiring restraint were more likely to have recently committed assault or battery and to have been brought in by the police. CONCLUSIONS: Enduring personal characteristics of patients relate neither to psychiatric emergency service assessments of current dangerousness nor to the decision to hospitalize. These determinations appear to be related to assessments of current patient state and immediate past behavior. PMID- 1928474 TI - A placebo-controlled, double-blind crossover study of fluoxetine in trichotillomania. AB - OBJECTIVE: It has been proposed by some investigators that trichotillomania, a disorder of chronic hair pulling, is a variant of obsessive-compulsive disorder, and some studies have suggested that the antiobessional agents clomipramine and fluoxetine are useful in treating this disorder. The authors investigated the efficacy of fluoxetine in the treatment of trichotillomania. METHOD: Twenty-one adult chronic hair pullers were recruited into an 18-week placebo-controlled, double-blind crossover study of fluoxetine, in doses up to 80 mg/day. The fluoxetine and placebo treatment phases consisted of 6-week trials of each agent separated by a 5-week washout period. Fifteen subjects (14 female and one male) completed the study; an additional female subject dropped out at 16 weeks after developing a drug reaction. RESULTS: No significant Drug by Period interactions were found in weekly subject ratings of hair pulling, weekly subject ratings of the urge to pull hair, weekly assessments of the number of hair-pulling episodes, or the estimated amount of hair pulled per week. CONCLUSIONS: The short-term efficacy of fluoxetine in the treatment of trichotillomania was not demonstrated in this study. PMID- 1928475 TI - Media distortion of the public's perception of recidivism and psychiatric rehabilitation. AB - OBJECTIVE: The public's perception about the success or failure of psychiatric rehabilitation is frequently dependent upon information received through the news media. The primary objective of this report is to present an example of how the news media can distort public perceptions of treatment outcome. METHOD: Verbatim quotations were presented from a television news series that alleged criminal recidivism by nine patients purportedly treated for various paraphilias at a large, community-based sexual disorders clinic. Brief case vignettes about each of the nine were then reviewed. This allowed for comparisons between what the media had alleged and what had actually occurred. RESULTS: Two of the nine cases were relatively minor instances of recidivism involving no genital contact, although the media presentation had either failed to report this or had suggested otherwise. A third case of alleged recidivism involved a patient who was evaluated but never actually treated by the clinic in the community. A fourth patient had refused recommended clinic treatment upon prison release, and a fifth patient had been discharged from treatment at the clinic because of noncompliance years before recidivating. Other cases presented contained additional misleading information. None of the nine cases was reported by the media in the context of a balanced approach that included treatment successes. Clinic staff were constrained from responding publicly to correct certain misinformation because of patient-psychiatrist privilege. CONCLUSIONS: Inaccurate media presentations about psychiatric rehabilitation that ignore treatment successes and focus only on alleged failures do a disservice to patients, mental health workers, and society at large. PMID- 1928476 TI - CT scan abnormalities and outcome of chronic schizophrenia. AB - The authors evaluated the relationship between brain morphological characteristics assessed by means of computerized tomography and the 2-year clinical and social outcomes of 18 patients with chronic schizophrenia. Cerebral structural abnormalities, especially cortical atrophy, were associated with a poorer outcome in several areas of clinical and social functioning. PMID- 1928477 TI - Correlation of Wisconsin Card Sorting Test performance with eye tracking in schizophrenia. AB - The authors studied the relationship between performance on the Wisconsin Card Sorting Test and on the Trailmaking-B test and measures of smooth pursuit eye movements in 12 patients with chronic schizophrenia and 12 normal volunteers. They found that performance on the Wisconsin Card Sorting Test was significantly correlated with measures of smooth pursuit eye movements in schizophrenic patients but not in normal subjects. Trailmaking-B scores, however, were unrelated to smooth pursuit eye movements in either group. PMID- 1928478 TI - Higher lifetime prevalence of respiratory diseases in panic disorder? AB - Current and past frequencies of respiratory diseases were assessed in 30 patients with panic disorder, 30 patients with obsessive-compulsive disorder, and 30 patients with eating disorders. Lifetime prevalence of respiratory disorders was significantly higher in patients with panic disorder (47%) than in patients with either obsessive-compulsive disorder (13%) or eating disorder (13%). Point prevalences showed no differences. PMID- 1928479 TI - Tricyclics and heart failure. PMID- 1928480 TI - Recent fluoxetine treatment and complications of tricyclic therapy. PMID- 1928481 TI - Serum sickness induced by fluoxetine. PMID- 1928482 TI - Effect of fluoxetine on patients with multiple sclerosis. PMID- 1928483 TI - Penile anesthesia associated with fluoxetine use. PMID- 1928484 TI - Association of fluoxetine with suicidal ideation. PMID- 1928485 TI - Potential interaction between warfarin sodium and fluoxetine. PMID- 1928486 TI - Fluoxetine and parkinsonism in patients taking carbamazepine. PMID- 1928487 TI - Buspirone augmentation of fluoxetine in a depressed child with obsessive compulsive disorder. PMID- 1928488 TI - Possible induction of psychosis by buspirone. PMID- 1928489 TI - Possible interaction between clozapine and lorazepam. PMID- 1928490 TI - Adverse reaction to generic alprazolam. PMID- 1928491 TI - Reporting of child abuse. PMID- 1928493 TI - Delayed onset of PTSD: delayed recognition or latent disorder? PMID- 1928492 TI - Case involving issues similar to those in Osheroff. PMID- 1928494 TI - Utilization of inpatient psychiatric facilities in wartime. PMID- 1928495 TI - Algorithms versus decision trees in DSM-III-R. PMID- 1928496 TI - Capitalization of diagnoses in DSM-IV. PMID- 1928497 TI - Alcoholic mood syndrome or major depressive disorder with alcoholism? A challenge for DSM-IV. PMID- 1928498 TI - Revising diagnostic criteria for delirium. PMID- 1928499 TI - Modifying the Wisconsin Card Sorting Test performance of schizophrenic patients. PMID- 1928501 TI - Issues in the 1990 presidential address. PMID- 1928500 TI - Irritable bowel syndrome in patients with panic disorder. PMID- 1928502 TI - Co-occurrence of deafness and infantile autism. PMID- 1928503 TI - Impact of insurance review process on inpatient care. PMID- 1928504 TI - Genetic and environmental factors in psychiatric disorders. PMID- 1928505 TI - Comments on self-injurious behaviour. PMID- 1928506 TI - Laws on reporting sexual abuse of children. PMID- 1928507 TI - Disturbed body image in inpatients with eating disorders. PMID- 1928509 TI - Benzodiazepine withdrawal. PMID- 1928508 TI - Disavowal of pregnancy: an adjustment disorder. PMID- 1928510 TI - Surreptitious use of medication by placebo subjects. PMID- 1928511 TI - Psychological comorbidity and length of stay. PMID- 1928512 TI - Position statement: Homosexuality and the Immigration and Naturalization Service. PMID- 1928513 TI - Position statement on child abuse and neglect by adults. PMID- 1928514 TI - "Why do (don't) you ask?" Transference and the desire (not) to know. AB - One of the criterial distinctions of psychoanalysis is its renunciation of indoctrination through suggestion. In spite of the fact that psychoanalysis is both an organized body of knowledge and a disciplined form of interpersonal influence, it regards an analyst who tells the analysand what to think or do as essentially doing harm by substituting a new form of prejudice and alienation for the preexisting form he is attacking. Even though an analyst regards his knowledge of psychoanalytic theory as adequate at a general level, this "truth" is not an adequate mode of discourse with an individual. Why not? It is a fact that analysands often do not accept an analyst's idea. However, the fundamental problematic of clinical psychoanalysis comes precisely at the point that the analysand would accept the analyst's idea, involving the distinction between a properly psychoanalytic cure and a transference cure. Psychoanalytic theory itself holds that unreflective incorporation of another's idea about oneself comes at the expense of autonomous and spontaneous self-revelation. Despite its resolute pursuit of new truths, the aim of psychoanalysis is less concerned with attaining specific ideas about unrecognized conflicts than it is with achieving a general attitude--that self-understanding requires a capacity to admit dubious and unwanted ideas and feelings that symptoms, dreams, and free associations bring to light. This "psychoanalytic" attitude permits a new type of discourse in which the person recognizes himself or herself through expression, rather than parrotting the analyst's (or others') words, or continuing rigidly to hide the truth of desire for oneself. In the long run, psychoanalysis offers to correct a primary misunderstanding: that one can acquire a comprehensively true image of oneself. As Barratt (1988) emphasizes, this transformation is tantamount to a change in personal epistemology for the analysand and a change in epistemological theory for the culture as a whole. In our culture, most analysts and lay people alike take for granted that the ego is an agent that is to be integrated and strengthened in order to direct one's life. Likewise, the unconscious is commonly regarded as a type of savage alter ego that must be mastered by the ego. According to Lacan's critique, the ego is a snare and a delusion for the patient, however highly commended by society it may be, because its very essence is to furnish the illusion of enduring self-knowledge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1928515 TI - Self-psychology and feminism: an integration and expansion. PMID- 1928516 TI - Some more speculations on Anna O. PMID- 1928517 TI - Freud's affair with Minna Bernays: his letter of June 4, 1896. PMID- 1928518 TI - The preoccupation with economic growth: an analysis informed by Horneyan theory. PMID- 1928519 TI - Injection drug use, mortality, and the AIDS epidemic. PMID- 1928520 TI - Those other STDs. PMID- 1928521 TI - Sociodemographic distribution of gonorrhea incidence: implications for prevention and behavioral research. AB - BACKGROUND: Despite a declining incidence during the AIDS era, gonorrhea remains the most frequently reported communicable disease in the United States. METHODS: During 1986 and 1987 we supplemented gonorrhea case reporting with laboratory surveillance in King County, Washington. Incidence rates were correlated with demographic variables. RESULTS: Overall incidence of gonorrhea was similar for men and women, but highest for 16- to 21-year-old females and urban Seattle residents. Incidence rates by ethnicity were Blacks, 3033; Native Americans, 843; Hispanics, 617; Asians, 190; and Whites, 121. Census tracts representing the lowest socioeconomic status (SES) quartile accounted for 58% of reported gonorrhea. Black female teenagers residing in the lowest SES urban areas had highest incidence rates: aged 14 to 15, 3.4%; 16 to 17, 10.4%; 18, 17.0%; and 19, 15.4%. Rates in female teenagers were even higher after adjustment for estimated proportion of those who were sexually experienced. CONCLUSIONS: Gonorrhea incidence is associated with age, gender, ethnicity, SES, and residence. Identification of populations at highest risk for gonorrhea can direct interventions against all sexually transmitted diseases. Clearly, interventions to alter high-risk behaviors must be initiated in early adolescence. PMID- 1928522 TI - Public health intervention in a cocaine-related syphilis outbreak. AB - BACKGROUND: Cocaine users and prostitutes are at high risk for syphilis, but disease control is difficult among these populations. During a cocaine-related syphilis outbreak in Chester, Pennsylvania, in 1989, we conducted a control program at sites where sex and drugs were sold. METHODS: During a 2-week period, investigators recruited persons from these sites for interview, serologic testing, and empiric treatment. RESULTS: Among 136 persons screened, 25 (18%) had early syphilis and 26 others (19%) had recent sexual contact with early syphilis patients. All were treated at initial screening at a cost of $402 and 12 investigator hours per case, compared to $470 and 20 hours per case when treated during routine investigator activities. This program may have contributed to a short-term decline in syphilis incidence in Chester by reducing the period of infectivity of these patients. CONCLUSIONS: Screening and empiric treatment of persons at sites where sex and drugs are sold can be useful in short-term control of cocaine-related syphilis outbreaks. PMID- 1928523 TI - Diverging gonorrhea and syphilis trends in the 1980s: are they real? AB - BACKGROUND: The purpose of this study was to evaluate whether the divergence in national trends of gonorrhea and syphilis from 1986 to 1989 in the United States was real and if overall trends masked a contemporaneous increase in both diseases in a core group. METHODS: We analyzed the following: (1) reported cases of gonorrhea and primary and secondary syphilis in the United States for the years 1981 to 1989, (2) gonorrhea screening results from six states for the years 1985 to 1989, and (3) reported cases of gonorrhea and primary and secondary syphilis by census tract for the years 1986 to 1989 in one city. RESULTS: The incidence of gonorrhea decreased 22% in the United States from 1986 to 1989 while the incidence of primary and secondary syphilis increased 59%. Among Blacks, syphilis incidence increased 100% and gonorrhea incidence decreased 13%; among Whites and Hispanics, the incidence of both diseases decreased. Results from gonorrhea screening among females in six states agree with gonorrhea incidence trends in those areas. Race-specific and census tract analyses of data from a number of metropolitan areas where overall rates diverged did not demonstrate a group in which the incidence of both diseases increased. CONCLUSIONS: We conclude that diverging trends of gonorrhea and syphilis from 1986 to 1989 are real and emphasize differences in the epidemiologic characteristics of these two sexually transmitted diseases. PMID- 1928524 TI - A multistate outbreak of hepatitis A caused by the consumption of raw oysters. AB - BACKGROUND: In August 1988 we investigated a multistate outbreak of hepatitis A caused by Panama City, Florida, raw oysters. METHODS: Cases of hepatitis A (HA) with onset in July-August 1988 were identified among persons who ate seafoods harvested in the coastal waters of Panama City, Florida. We conducted a case control study, using eating companions of case-patients, and calculated attack rate (AR) per 1000 dozen raw oysters served. Enzyme immunoassay (EIA) and a polymerase chain reaction (PCR) technique were performed on samples of raw shellfish obtained from Panama City coastal waters. RESULTS: Sixty-one case patients were identified in five states: Alabama (23), Georgia (18), Florida (18), Tennessee (1), and Hawaii (1). We found an increased risk of HA for raw oyster eaters (odds ratio = 24.0; 95% confidence interval = 5.4-215.0; P less than .001). The AR of HA in seafood establishments was 1.9/1000 dozen raw oysters served. The EIA and PCR revealed HA virus antigen and nucleic acid in oysters from both unapproved and approved oyster beds, in confiscated illegally harvested oysters, and in scallops from an approved area. CONCLUSIONS: The monitoring of coastal waters and the enforcement of shellfish harvesting regulations were not adequate to protect raw oyster consumers. More emphasis should be placed on increasing public awareness of health hazards associated with eating raw shellfish. PMID- 1928525 TI - Bleach programs for preventing AIDS among i.v. drug users: modeling the impact of HIV prevalence. AB - BACKGROUND: The growing importance of drug use as a mode of HIV transmission has led to increased attention to AIDS prevention among intravenous drug users (IVDUs). This analysis examines the effectiveness of bleach distribution, a program to prevent HIV transmission via shared needles. METHODS: We used a Markov model to assess the role of the initial HIV prevalence among drug users in determining the effectiveness of bleach programs. The model incorporates survey data on risk behaviors and published information describing HIV incubation and mortality. It predicts life expectancy for cohorts of IVDUs with and without a bleach program to estimate program effectiveness. RESULTS: We found that bleach programs can produce the greatest life-year savings in areas of low HIV prevalence. In the lowest prevalence scenario (0.02 initial prevalence), initiation of the program resulted in a projected savings of 2.3 life years per HIV-negative drug user, compared with 1.7 and 1.3 years under medium (0.25) and high (0.60) prevalence, respectively. CONCLUSIONS: While bleach programs are beneficial in all groups of IVDUs, these results highlight the advantages of introducing bleach programs early, when prevalence is still comparatively low in a drug-user population. PMID- 1928526 TI - Inpatient morbidity among HIV-infected male soldiers prior to their diagnosis of HIV infection. AB - BACKGROUND: A natural history study of human immunodeficiency virus (HIV) disease was carried out among 1575 HIV-infected US Army men and 6220 demographically similar uninfected soldiers. Inpatient morbidity occurring up to 8 years prior to the date of HIV infection diagnosis among those men who became HIV infected was evaluated for both groups. METHODS: Incidence density rates were calculated for hospital admissions. Poisson regression was used to assess the trend in hospital admissions among those subsequently diagnosed with HIV infection. Prevalence ratios for discharge diagnoses were also calculated. RESULTS: Sixteen diagnoses/diagnosis categories occurred statistically more frequently among subsequently HIV diagnosed individuals than among those who remained uninfected. Among these were hepatitis B and abscess of anal/rectal region (6 to 8 years prior to HIV infection diagnosis); unspecified viral infection, enlarged lymph nodes, syphilis (3 to 5 years prior to HIV infection diagnosis); and diagnoses suggestive of acute retroviral syndrome (1 to 2 years prior to HIV infection diagnosis). CONCLUSIONS: Data such as these may provide useful information to HIV surveillance efforts regarding patterns of morbidity experienced prior to HIV infection as well as to health care providers regarding patients at high risk for becoming infected with HIV. PMID- 1928527 TI - Utilization of health services in a cohort of intravenous drug users with known HIV-1 serostatus. AB - BACKGROUND: Intravenous drug users (IVDUs) with human immunodeficiency virus (HIV) infection and AIDS often have no health insurance or rely on public programs to finance their health care. We examined the independent contributions of HIV serostatus, clinical symptoms, CD4 cell counts, and health insurance to utilization of health services among 1881 intravenous drug users in Baltimore, Maryland. METHODS: Participants in an ongoing natural history study of HIV were informed of HIV serostatus and seropositives were informed of CD4 cell counts; 6 months later, participants were administered a questionnaire concerning self reported use of health services, insurance coverage, and HIV-related symptoms. RESULTS: Of 1881 participants, 67% had health insurance (including Medicaid), 48% had at least one outpatient visit, and 12% had at least one inpatient visit within the prior 6 months. The proportion of the study population that was HIV-1 seropositive was 32%. In multivariate analysis, the single most important predictor of health care utilization was the presence of two or more HIV-related clinical symptoms. HIV positive serostatus alone or known low CD4 counts were not significantly associated with use of health care services. CONCLUSIONS: These data suggest that HIV seropositive IVDUs are not receiving recommended preventive care. Additional efforts will be needed to ensure that HIV-seropositive drug users participate in currently recommended protocols for early treatment of asymptomatic HIV-1 infection. PMID- 1928528 TI - Risk factors for shooting gallery use and cessation among intravenous drug users. AB - BACKGROUND: Shooting galleries, locations where intravenous drug users (IVDUs) can rent or borrow needles and syringes, are a high-risk environment for HIV-1 transmission. This study investigates risk factors for lifetime attendance at shooting galleries and differentiates characteristics of those who continue to frequent shooting galleries and those who have stopped. METHODS: We interviewed 2615 active IVDUs in Baltimore in 1988 and 1989 and determined patterns of IV drug use, sociodemographics, and HIV-1 serostatus as related to persistence vs cessation of shooting gallery use. RESULTS: Over half (52%) of active IVDUs reported ever using a shooting gallery, with 33% reporting use within the prior 3 months. In multivariate analysis, lifetime shooting gallery use was associated with male gender, homosexuality/bisexuality, low socioeconomic status, Black race, and heavier drug involvement. Persistent shooting gallery users were more frequently male, homosexual/bisexual, homeless, less educated, and started IV drug use more recently compared with those who ceased going to shooting galleries. CONCLUSIONS: Shooting gallery attendance may be pragmatic from a sociological and economic perspective, but it carries with it a heightened risk of acquiring HIV-1 infection. PMID- 1928530 TI - Leptospirosis on Kauai: investigation of a common source waterborne outbreak. AB - During the summer of 1987, a common source waterborne outbreak of leptospirosis occurred on the island of Kauai in the state of Hawaii. Eight leptospirosis cases were identified using the microscopic agglutination test. Methodologic weaknesses in this technique were responsible for the initial missed diagnosis on six of the eight cases. All cases had repeated exposure to the Waimea River. A wide array of animal reservoirs and optimal water conditions may have been factors in this outbreak. PMID- 1928529 TI - Impact of a geriatric assessment unit on subsequent health care charges. AB - BACKGROUND: In a recent randomized controlled trial assessing the efficacy of an inpatient geriatric assessment unit (GAU), we demonstrated that patients assigned to the unit were less likely than those in the usual care group to be admitted to a nursing home and more likely to remain living in the community. Despite evidence of benefits of GAU care, questions remain about its cost. We examine the impact of GAU treatment on subsequent health care charges. METHODS: Sequential referrals of elderly disabled patients considered at risk for institutionalization or likely to improve with rehabilitation were randomized to the GAU or to usual care. Charge data were collected on utilization of a wide variety of health care services starting at the point of randomization. RESULTS: The group randomized to the GAU experienced significantly higher rehabilitation charges per participant ($10,583 vs $2066, P = .0001), but lower mean nursing home charges ($1798 vs $3426, P = .004). Total health care charges per participant over the 1 year follow-up were greater for the GAU group ($28,406 vs $16,444, P = .004). When charges were adjusted per year of life survived, the GAU group still showed a substantial (but nonsignificant, P = .10) increase in total charges. However, when charges were adjusted per day subsequently spent residing in the community, adjusted total charges were similar between the two groups. CONCLUSIONS: Our results indicated that improved outcomes from GAU care require an investment in rehabilitation that is not totally offset by decreased institutional charges in the following year. PMID- 1928531 TI - Timeliness of national reporting of communicable diseases: the experience of the National Electronic Telecommunications System for Surveillance. AB - The timeliness of reporting four nationally notifiable diseases was examined using data reported via the National Electronic Telecommunications System for Surveillance. Timeliness of reporting varied by disease (bacterial meningitis: median 20 days; salmonellosis: median 22 days; shigellosis: median 23 days; and hepatitis A: median 33 days) and by state. These findings indicate a need to standardize surveillance definitions and to account for reporting differences between states in interpreting regional disease trends or detecting multistate disease outbreaks. PMID- 1928532 TI - The association between congenital syphilis and cocaine/crack use in New York City: a case-control study. AB - From 1987 to 1989, an epidemic of congenital syphilis was observed in New York City. A case-control study was done to assess the association between various maternal risk factors and congenital syphilis. Independent of the effect of other factors, the odds of being exposed to cocaine were 3.9 times greater among cases than controls (95% confidence interval, 2.8-5.3). This study suggests that the epidemic of congenital syphilis may be related to the increase in cocaine/crack use among delivering mothers. PMID- 1928534 TI - Self-disclosure of HIV infection to sexual partners. AB - Self-disclosure of HIV infection to current sexual partners was examined in 138 seropositive men, mostly lower income Hispanics, from Los Angeles. Forty-five percent had been sexually active since learning their serostatus. Of these, 52% had kept their infection secret from one or more partners. The likelihood of disclosure decreased in direct proportion to the number of partners. Nondisclosure occurred in conjunction with unprotected receptive and insertive anal intercourse. Potential factors promoting nondisclosure are discussed. PMID- 1928533 TI - Human papillomavirus, gonorrhea, syphilis, and cervical dysplasia in jailed women. AB - We assessed the prevalence of human papillomavirus (HPV) by cervicovaginal lavage and Southern blot and inquired about behavioral risk factors for cervical disease and sexually transmitted diseases by interview in 114 female detainees at a large New York City jail. Of the women screened, 8% had abnormal Pap smears, 35% had HPV, 7% had gonorrhea, and 22% had serologic syphilis. Given the high rates of HPV infection and cervical cytology, Pap smears should be a routine intake procedure for incarcerated women. PMID- 1928535 TI - Immunoglobulins and growth parameters at birth of infants born to HIV seropositive and seronegative women. AB - Health characteristics of neonates born to human immunodeficiency virus (HIV) seropositive (n = 63) and HIV seronegative (n = 57) women were compared. No significant differences were found between the two infant groups for sociodemographic characteristics, mode of delivery, Apgar scores, gestational age, growth parameters, or immunoglobulin levels. Furthermore, no differences were detected in a subgroup of infants later confirmed to have HIV infection (class P-2). Maternal HIV infection does not appear to affect newborn health characteristics. PMID- 1928536 TI - The impact of HIV on the usefulness of sputum smears for the diagnosis of tuberculosis. AB - In a developing country, 289 patients were examined for active pulmonary mycobacterial disease (sputum smear and culture) and HIV infection (serology) to compare the sensitivity and positive predictive value of sputum smears for diagnosing pulmonary tuberculosis in patients with and without antibodies to HIV. Seventy-nine percent of HIV-seronegative vs 66% of HIV-seropositive patients with positive cultures for Mycobacterium tuberculosis were smear positive (P less than .05), and a positive sputum smear predicted the presence of M. tuberculosis in 90% of HIV seronegative vs 80% of HIV seropositive patients (P less than .05). In our opinion, HIV did not significantly compromise the diagnostic utility of the sputum smear. PMID- 1928537 TI - Human exposure to rabies from pet wild raccoons in South Carolina and West Virginia, 1987 through 1988. AB - During 1987 and 1988, exposures to eight pet wild raccoons in South Carolina and West Virginia resulted in administration of rabies post-exposure prophylaxis to 19 children and 26 adults. All eight raccoons appeared normal at the time of capture, and three had no signs of illness when sacrificed. The direct medical cost resulting from these exposures was $23,714 ($527 per person). Regulations and public education may help decrease this type of rabies exposure. PMID- 1928538 TI - Canine seroprevalence and the distribution of Ixodes dammini in an area of emerging Lyme disease. AB - This study evaluates the relative usefulness of canine serosurveys to predict risk of exposure in an area of emerging Lyme disease by comparing the distribution of canine seroprevalence with that of vector ticks. From 16 veterinary clinics throughout the State of Maine, 828 canine sera were obtained during the heartworm-testing months of April and May 1989 and measured for anti Borrelia antibodies by enzyme-linked immunosorbent assay. In the same year, 1605 ticks, including 585 Ixodes dammini, were collected from pets, humans, small mammals, and deer. Thirty-six dogs were seropositive, 28 of which had not traveled to endemic areas. Eighty-nine percent of all seropositive dogs were from towns within 20 miles (32 km) of the coast; the great majority lived within 5 miles (8 km) of tidewater (odds ratio =4.45, P = .002). Positivity varied from 17% in a southern coastal clinic to 0% in four northern clinics. Of 585 I. dammini identified, all but 5 (99.1%) were also from towns within 20 miles of the coast. Comparison of I. dammini submissions with those of another commonly found tick, Ixodes cookei, corroborated this predominantly coastal distribution. Canine seropositivity generally coincided with this coastal range. These data predicted areas of risk for human Lyme disease, although the prevalence of reported cases remained low. PMID- 1928539 TI - Situational factors associated with AIDS risk behavior lapses and coping strategies used by gay men who successfully avoid lapses. AB - While most gay men have reduced behavior practices at high risk for HIV infection, there is growing evidence that many also lapse to unsafe sex. This study examined situational factors related to risk behavior lapses as well as coping strategies used by men who successfully resist lapse urges. A convenience sample of 470 men patronizing gay bars or attending social organization meetings in four cities was surveyed. Forty-five percent of men were classified as "lapsers" (those who had had unprotected anal intercourse in the previous 6 months) and 24% were classified as "resisters" (those who successfully resisted urges to engage in this behavior). All provided information concerning the importance of factors related to the most recent occurrence of either unsafe sex or resisting unsafe urges. Most episodes of unsafe sex occurred outside monogamous relationships and with partners of unknown HIV serostatus, although simply inquiring about partner serostatus was relatively common. Lapsers rated affectionate feelings and wishing to please a partner as well as spontaneity of unsafe sex as the most important situational factors surrounding high-risk behavior. Resisters of unsafe sex urges reported active cognitive self-guidance, experience in safe sex, and recall of both AIDS fears and safety benefits as their most important coping strategies. Gay men who continue high-risk behavior may be overrelying on partner reports of negative serostatus. Lapse prevention approaches tailored to situations that create increased risk vulnerability must be developed. Teaching skills already used by men who successfully resist unsafe sex urges might be one approach. PMID- 1928540 TI - The ban on cigarette vending machines in Bloomington, Minnesota. PMID- 1928541 TI - Marquette County Health Department: food service sanitation--doing better with less. PMID- 1928542 TI - Lead paint abatement--definition and outcomes debated. PMID- 1928543 TI - Acceptance of the female condom by Latin- and African-American women. PMID- 1928544 TI - APHA, the journal, and alcohol advertising--the ethics involved. PMID- 1928545 TI - Recommendations on quality control and quality assurance in anatomic pathology. Association of Directors of Anatomic and Surgical Pathology. PMID- 1928546 TI - Cutaneous Kikuchi's disease. PMID- 1928547 TI - Lymphocytic gastritis. PMID- 1928548 TI - Mesothelioma metastasis. PMID- 1928549 TI - Solitary congenital fibromatosis (infantile myofibromatosis) of bone. AB - Congenital fibromatosis is a rare and benign myofibroblastic tumor that may occur in either a solitary or multicentric form. The soft-tissue form of this entity is well recognized. This report analyzes the clinical and pathologic features of 14 cases of congenital fibromatosis in which the tumor existed as a solitary lesion in bone. Most of the tumors (71%) were in patients who were 2 years old or younger. All but one tumor involved the craniofacial bones. Radiographically, they were purely lucent lesions in which a sclerotic rim was visible in each skull lesion. The myofibroblastic appearance closely resembled the microscopic features seen in the soft-tissue counterpart. For appropriate surgical management, it is imperative to recognize that this tumor occurs as a solitary lesion in bone and that it is distinct from other, more aggressive fibrous lesions. PMID- 1928550 TI - Nodular fasciitis. Its morphologic spectrum and immunohistochemical profile. AB - Although nodular fasciitis (NF) is a well recognized pseudosarcomatous proliferation, it continues to cause diagnostic problems. We reviewed the clinical, histologic and immunohistochemical features of 53 lesions from 30 male and 23 female patients, ages 8-76 years, that involved the upper and lower extremities, trunk, and head and neck. Sizes ranged from 0.6 to 6.5 cm. The morphologic spectrum was broad, including the classic pattern of delicate fibroblasts suspended in a myxoid matrix, granulation tissue-like areas, solid and whorled myofibroblastic proliferations with multinucleated cells, mucoid cysts, and so-called "ancient" forms with dense, refractile strands of keloid like collagen. Nodular fasciitis was correctly diagnosed in 23 cases (43%); a sarcoma was diagnosed in 11 (21%). A characteristic immunohistochemical profile emerged wherein 49 of 53 cases stained for smooth-muscle and muscle-specific actins, vimentin, and KP1 (a histiocyte marker), indicating dual myofibroblastic and histiocytic differentiation. None of the lesions expressed keratin, S-100 protein, or desmin. Knowledge of the immunohistochemical profile of nodular fasciitis and its overlap with certain sarcomas can decrease the likelihood of misdiagnosis. PMID- 1928551 TI - Adrenocortical oncocytoma. A true nonfunctioning adrenocortical tumor. AB - We studied three cases of adrenocortical neoplasms that were detected incidentally after radiological examination of the abdomen. These cases did not demonstrate any clinical evidence of adrenocortical abnormalities, such as virilization. Macroscopically, the tumors were light to dark tan on cut surface. Light-microscopic examination revealed compact cells with abundant lipid-sparse eosinophilic cytoplasm and occasional enlarged nuclei. In one case, ultrastructural observation demonstrated abundant mitochondria. Immunohistochemical examination of all of the adrenocortical steroidogenic enzymes showed that none of the cases had immunoreactivity. No mitotic activity and no vascular invasion was observed. The postoperative course were uneventful. The follow-up interval varied from 8 to 27 months. These three neoplasms apparently represent the first reported cases of adrenocortical oncocytoma. They can be considered true nonfunctioning adrenocortical neoplasms because steroidogenic enzymes required for corticosteroid biosynthesis were not expressed in the tumor cells. PMID- 1928552 TI - Recurrence in noninvasive endometrial carcinoma. Relationship to uterine papillary serous carcinoma. AB - In a series of 227 consecutive operable clinical stage I endometrial carcinomas, there were 28 recurrences. In seven of these cases, no myometrial or vascular invasion was demonstrable. Recurrence in these seven noninvasive cases was strongly associated with papillary serous carcinoma, even when present only focally or manifested by typical cytological features in the absence of well formed papillae. An association with foci of clear cell carcinoma was also seen, as was direct evidence in two cases of synchronous ovarian serous carcinoma, one in situ. PMID- 1928554 TI - Littoral cell angioma. A novel splenic vascular lesion demonstrating histiocytic differentiation. AB - Seventeen cases of a novel type of vascular tumor of the spleen are described. The lesions, whose size ranges from minute foci to large nodules almost completely replacing the splenic tissue, are composed of anastomosing vascular channels resembling splenic sinus and have irregular lumina, often featuring papillary projections and cyst-like spaces; they are lined by tall endothelial cells that slough off into the vascular lumina and show hemophagocytosis. Atypical cells are absent and mitotic activity very low. In contrast to normal sinus endothelia, which express only FVIIIag, neoplastic cells express both endothelial (FVIII-AG, BMA 120) and histiocytic (KP1, lysozyme) antigens; occasionally S-100 protein is also present. The morphologic and immunohistochemical findings in this tumor reflect the dual differentiation potential of the reticuloendothelial cells lining the splenic sinus, justifying the term littoral cell angioma, and recognize a distinct entity that is different from other vascular lesions of the spleen, notably angiosarcoma. This distinction is all the more important because the clinical behaviour of this lesion is apparently benign. PMID- 1928553 TI - Kaposi-like infantile hemangioendothelioma. A distinctive vascular neoplasm of the retroperitoneum. AB - Retroperitoneal soft-tissue tumors are rare in infancy. In this report, we describe a distinctive hemangioendothelioma occurring in the retroperitoneum of a 10-month-old baby girl. This lesion was complicated by obstructive jaundice, intestinal obstruction, and thrombocytopenia (Kasabach-Merritt syndrome) leading to intracranial hemorrhage. The microscopic features of this tumor, characterized by infiltrative lobules of spindle cells and capillaries, are distinct from those of other well-recognized vasoformative tumors. In some areas, the tumor shows a striking resemblance to Kaposi's sarcoma; criss-crossing fascicles of spindle cells are interspersed with narrow vascular spaces, but PAS-positive hyaline globules are absent. The tumor can also be distinguished from the cellular hemangioma of childhood by its well-formed spindle cell fascicles. Several histologically similar cases have been reported. All of them occurred in the retroperitoneum of infants and were frequently complicated by Kasabach-Merritt syndrome. We therefore propose the designation "Kaposi-like infantile hemangioendothelioma" for this unusual neoplasm. PMID- 1928556 TI - Argyrophilic carcinoma of the male breast. A neuroendocrine tumor containing predominantly chromogranin B (secretogranin I). AB - Argyrophilic tumors were diagnosed in 28 of 134 (20.8%) consecutive male patients who had a carcinoma of the breast removed between 1961 and 1990. Histologically, most argyrophilic tumors showed uniform cellularity and prevalent expansive growth. Ultrastructural observation disclosed the presence of electron-dense cored granules in the cytoplasm of the tumor cells. By immunocytochemistry, 17 of 28 argyrophilic tumors (60.7%) contained chromogranin B (secretogranin I) immunoreactive cells, whereas chromogranin A was present in four of these 17 tumors only (14.2%). Immunoblotting studies showed chromogranin B immunoreactivity similar to that found in normal neuroendocrine cells. Despite these findings, which would argue for a distinct morphologic and immunochemical entity, no statistically significant differences between argyrophilic and common male breast carcinomas were found when a number of clinicopathologic features and relapse-free survival were considered. PMID- 1928557 TI - Chromogranin A and B in adenomas of the pituitary. An immunohistochemical study of 42 cases. AB - Forty-two pituitary adenomas (10 prolactinomas; three ACTH-, nine GH-, two FSH- and two TSH-secreting adenomas; and 16 clinically nonfunctioning null cell adenomas) were investigated immunohistochemically with antibodies against chromogranin A and B as well as ACTH, GH, prolactin (PRL), FSH, LH, TSH, and alpha-HCG antibodies. For the demonstration of chromogranin B, two different antibodies were used--e.g., a polyclonal antihuman antibody and an antiserum against a synthetic peptide (DK-21, chromogranin B 306-326) present in the chromogranin B amino acid sequence. All tumors were positive for both chromogranin B antibodies. Chromogranin A was found in FSH- (two of two) and TSH- (two of two) secreting adenomas; it was also found in a focal distribution in ACTH- (one of three) and GH- (four of nine) secreting adenomas. Thirteen of 16 null cell adenomas contained chromogranin A, whereas no chromogranin A was found in prolactinomas. We conclude that null cell adenomas may arise either from FSH/LH or TSH cells (null cell adenomas with both chromogranin A and B positivity) or from ACTH, GH, or PRL cells (the respective tumors are only positive for chromogranin B). Chromogranin B may be used as a universal marker for pituitary adenomas. PMID- 1928555 TI - Reliable and cost-effective paraffin section immunohistology of lymphoproliferative disorders. AB - We studied 110 neoplastic and reactive lymphoid proliferations with three monoclonal antibodies--CD20 (L26), CD43 (Leu22), and CD45RO (UCHL1)--on B5-fixed, paraffin-embedded tissue to evaluate the utility of this panel as an immunotypic screen of such lesions. All cases were initially immunotyped by conventional methods. Genotyping by Southern blot hybridization was also done in 54 cases. Seventy-four of 79 malignant lymphomas and both of two hairy cell leukemias were of B-cell origin; and five lymphomas were defined as T-cell lineage. Lineage assignment was identical for paraffin section immunohistology and conventional immunotyping in 73 of 76 B cell and all of five T-cell tumors. CD20 was reactive with 73 of 76 B-cell tumors. CD43 was reactive with 12 of 74 B-cell lymphomas, and CD20/CD43 coexpression was seen in 11 of these cases. CD43 and CD45RO marked all of five and three of five T-cell lymphomas, respectively. Lineage assignment was identical for paraffin immunohistology and genotyping in 48 of 50 cases with identifiable gene rearrangements. Twenty-four nonneoplastic and five Hodgkin's disease cases that were studied also showed similar immunoreactivity patterns by both paraffin and conventional immunotypic methods. This panel of three monoclonal antibodies is an efficient, cost-effective approach for immunotyping most lymphoid proliferations in paraffin sections. Nevertheless, the pathologist should always try to obtain fresh or frozen tissue to aid in resolving occasional discrepant cases, to establish clonality in morphologically ambiguous ones, and to profile prognostically important phenotypic deletions. PMID- 1928558 TI - Bleeding due to colorectal atheroembolism. Diagnosis by biopsy of adenomatous polyps or of ischemic ulcer. AB - Atheroembolism, although not infrequent at autopsy, is seldom identified in life, when it may present as a multisystem disease involving lower limbs, kidney, and gastrointestinal (GI) tract. Diagnosis of isolated GI involvement usually requires examination of surgically resected tissue, because recognition by endoscopic GI biopsy is exceptional. We diagnosed colorectal atheroembolism by biopsy in four patients. All were elderly (68-80 years old) and had generalized atheroma, including aortic aneurysms. Three patients had sudden onset of frank rectal bleeding with clots or bloody diarrhea, lower abdominal discomfort, and tenderness. Biopsy revealed atheroemboli in a rectal ischemic ulcer and in colorectal adenomatous polyps. In all three, disease resolved on conservative management and did not recur during the period of follow-up. In the fourth patient, asymptomatic atheroembolism was identified in an adenomatous polyp at the splenic flexure. Extraintestinal disease attributable to atheroembolism was not present in any of the patients. Atheroembolism with manifestations confined to the colon may sometimes be diagnosed by biopsy, appears to be more frequent than currently recognized, and may present a diagnostic challenge as a self limited episode of rectal bleeding. PMID- 1928559 TI - Renal angiomyolipoma with sarcomatous transformation and pulmonary metastases. AB - We report the case of a 49-year-old woman with a large renal angiomyolipoma that invaded the liver. In some areas, the tumor had the appearance of a typical angiomyolipoma; however, it also had foci where the spindle cells of the lesion showed marked cytologic atypia and mitotic activity, giving it the appearance of a high-grade sarcoma. Immunohistochemical studies demonstrated expression of vimentin, desmin, and muscle-specific actin by the sarcoma cells; these findings were consistent with leiomyosarcoma. A second, small typical angiomyolipoma was also present in the kidney. In addition, the liver exhibited focal nodular hyperplasia. Three weeks after resection of the primary renal tumor, pulmonary metastases were diagnosed by fine-needle aspiration biopsy. This is the first report of a case of angiomyolipoma with sarcomatous transformation and biopsy proven metastatic disease. PMID- 1928560 TI - Encapsulated medullary carcinoma of the thyroid. A morphologic study including immunocytochemistry, electron microscopy, flow cytometry, and in situ hybridization. AB - An unusual encapsulated medullary carcinoma of the thyroid is reported. Immunocytochemistry and electron microscopy did not prove conclusively the cytogenesis of the tumor; however, in situ hybridization, by demonstrating the presence of calcitonin mRNA, revealed that the tumor is of C-cell derivation. Because these tumors have an unpredictable biologic behavior, it seems more appropriate to designate them as encapsulated medullary carcinoma than as C-cell adenoma. Immunocytochemistry for calcitonin and carcinoembryonic antigen as well as flow cytometry for DNA ploidy may be valuable techniques to assess prognosis of these tumors. PMID- 1928561 TI - Photographic reproduction of anatomic specimens using ultraviolet illumination. AB - The black-and-white photographic reproduction of the surfaces of anatomic specimens is often difficult due to the uniformity of their color and their natural translucency. The standard illumination for black-and-white gross photographs, which uses white light with a broad range of wavelengths, results in a varying penetration of light into a translucent object; therefore, it precludes a sharp focus. The problem of translucency may be largely overcome by the use of ultraviolet illumination. Ultraviolet radiation (in the range of 320-400 nm provided by black-light sources) provides a more monochromatic light with limited penetration through the surface. As a result, the rays are either reflected or absorbed, and the scatter within the tissue layers is minimal. The combination of limited penetration and more regular reflection produces a sharper focus of the returned light. Thus it provides heightened image clarity and contrast. PMID- 1928562 TI - Correlation between histopathology, immune response, clinical presentation, and evolution in Leishmania braziliensis infection. AB - Skin biopsies from 221 parasitologically confirmed cases of tegumentary leishmaniasis caused by Leishmania braziliensis spp. were evaluated with respect to histopathology, the qualitative and quantitative nature of the cellular infiltrate, and the presence of Leishmania amastigotes. These variables were cross correlated with the Leishmania-specific immune response, clinical presentation, and response to treatment. Physical evidence of prior leishmanial lesions was associated with the absence of amastigotes (P less than or equal to 0.001) and the presence of giant (P = 0.03) and epitheloid cells (P = 0.03) in the biopsy of the active lesion. The presence of amastigotes was inversely related to the duration of the lesion (P less than or equal to 0.001) and the presence of eosinophils (P less than or equal to 0.01), whereas the presence of adenopathy (P = 0.01), necrosis (P = 0.001), histiocytes (P = 0.001), and increased serum antibody titer (P = 0.02) were directly associated with the presence of amastigotes. The lymphocyte transformation response was correlated with the presence of granulomas (P = 0.001), but showed no correlation with cutaneous delayed type hypersensitivity. The presence of epithelioid (P = 0.04) and giant cells (P = 0.03) was associated with less drug being required to achieve healing. In contrast, necrosis was associated with a greater amount of drug to achieve healing (P = 0.05). The observed correlations between tissue responses and immune and clinical parameters provide further evidence for the role of antibody and other soluble mediators of the cellular immune response in the evolution of disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928563 TI - Concurrent infection with Leishmania donovani and Leishmania major in a Kenyan patient: clinical description and parasite characterization. AB - Leishmania isolates aspirated a few months apart from the spleen of an indigenous adult male kala-azar patient from Baringo District, Kenya, were biochemically characterized and compared. The patient lived within a dual focus of L. donovani kalazar and L. major cutaneous leishmaniasis. A primary Leishmania isolate from splenic aspirates was cryopreserved (NLB-294). The patient was treated with sodium stibogluconate for kala-azar and discharged. Three months later, he had clinical relapse and returned for retreatment. During his second visit, the patient participated in a diagnostic study in which urine and nasopharyngeal samples were cultured for leishmaniasis. Urine, nasopharyngeal, and splenic samples were positive for Leishmania. Secondary isolates from splenic (NLB-294-I) and urine (NLB-318) cultures were cryopreserved and characterized by cellulose acetate electrophoresis (CAE) using 20 enzymes. Whereas the urine isolate was typed as L. donovani, the splenic aspirate culture revealed a mixed infection with L. donovani and L. major. The primary isolate (NLB-294) was then characterized and also showed a mixed infection. To exclude the possibility of protein post-translational modifications in electrophoretic assays, the primary and secondary isolates were grown and processed under identical cultural and lysis conditions, and compared using CAE. The results were identical to the first electrophoretic assays showing mixed promastigote banding patterns. Stationary phase promastigotes of the secondary splenic isolate (NLB-294-I) inoculated subcutaneously, intraperitoneally, and intracardially into Syrian hamsters and BALB/c mice produced both kala-azar and cutaneous leishmaniasis within 6.5 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928565 TI - Failure of falciparum malaria prophylaxis by mefloquine in travelers from West Africa. AB - Due to the spread of chloroquine-resistant strains of Plasmodium falciparum in French speaking parts of Africa, we have found it necessary to prescribe mefloquine for antimalaria prophylaxis to travelers to this area. Weekly doses of 125 or 250 mg have been recommended for short journeys. In spite of this regimen, 16 documented cases of falciparum malaria in travelers have been recorded in the Bordeaux hospital center since October, 1988. Fifteen of these patients were tourists returning from West African countries, and one was an Ivorian student who had been on vacation to his home country. Nine of these patients were evaluated and found to have high plasma mefloquine levels. This report strongly supports the existence of mefloquine-resistant falciparum malaria in West Africa, especially in Sierra Leone, Burkina Faso, and Cote d'Ivoire. PMID- 1928564 TI - Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. AB - The protective effect of African IgG antibodies against Plasmodium falciparum malaria was investigated by passive transfer in Thai patients. Sera from 333 African adults were collected in the Cote d'Ivoire and subjected to extensive screening. One hundred fifty-three samples were discarded for safety reasons, and IgG was extracted from those remaining under conditions allowing their use by the intravenous (iv) route. Eight Thai patients with P. falciparum parasitemia were treated by iv inoculation of the IgG: six with a 100 mg/kg dose given over three days, one with a single 20 mg/kg dose, and one with a single 200 mg/kg dose. To ensure a safety margin of at least 48 hours, subjects were chosen among patients having a recrudescent parasitemia following quinine treatment failure at the RI level. At that stage, symptoms were mild or absent and parasitemia was low but increasing (range 4, 200-9,000/microliters). The IgG pool exerted a profound, stage-specific, but non-sterilizing effect on each of the strains tested, and proved to be safe. Asexual parasitemia decreased by a mean 728-fold (range 46 1,086), while gametocytes were unaffected. Clearance of parasites and symptoms was as fast or faster than with drugs, and was consistent in the eight patients treated, suggesting that target antigens were equally expressed in geographically remote isolates. In peripheral blood smears, no mature forms were seen at any time during the followup, which does not support the hypothesis that reversal of cytoadherence occurred. After the disappearance of the transferred antibodies, recrudescent parasites from three patients were found to be susceptible to the same extent (mean decrease of 1,310-fold) to the same IgG preparation, indicating that selection of parasites able to escape the effect of antibodies had not occurred. No adverse side-effects were detected during the followup, which lasted one year. PMID- 1928566 TI - Bancroftian lymphadenopathy: a histopathologic study of fifty-eight cases from northeastern Brazil. AB - Histologic study of Bancroftian lymphadenopathy in 58 patients originating from an endemic area revealed a wide range of tissue reactions to the filarial worms. In seven patients (12.0%), no attendant inflammation or parasite damage was observed. A mild-to-intense nongranulomatous chronic lymphangitis was found in 12 patients (20.7%). Granulomatous reactions with variable composition were the most common pattern observed (37 patients, 63.8%); fibrotic lesions containing calcified worms were present in 13 of these patients. Epithelioid granulomas without worms, associated either with granulomatous reactions to the worms (seven patients) or nongranulomatous lymphangitis (two patients), were also detected. Lymphoid hyperplasia and lymphatic dilation were constant, and eosinophil infiltration was usually remarkable. These findings were compared with those reported from nonendemic populations and emphasize the parallelism between the pathologic findings and the immune responsiveness reported in such patients. PMID- 1928567 TI - A new focus of Schistosoma haematobium/S. intercalatum hybrid in Cameroon. AB - Terminal-spined schistosome eggs were found in both stool and urine specimens of a high proportion of infected individuals in Kinding Njabi, a village located in a savannah/forest ecotone of Center Province, Cameroon. Infections with terminal spined schistosomes are not common in that region and first appeared in Kinding Njabi in the mid-1980s. The village population, determined by house-to-house census in 1986, was 345. Of 302 stool samples examined by a thick smear technique, 58 (19%) were positive, and of 320 urine samples examined by sedimentation, 40 (12%) were positive. Twenty-six (37%) of a total of 71 infected persons passed eggs in both stool and urine. Egg size distribution and morphology were similar to previous reports for Schistosoma haematobium/S. intercalatum hybrids. Bulinus forskalii was the only snail found during extensive surveys in and around Kinding Njabi; infected snails were recovered from several temporary habitats. This focus is of particular interest because it represents the first report of transmission of hybrid schistosomes outside of the hybrid zone. Interviews with villagers and local health officials suggest that schistosomiasis was introduced by immigrants from Loum, a town approximately 100 km southwest of Kinding Njabi, where S. haematobium, S. intercalatum, and their hybrid are known to exist. Results from snail host specificity studies using the Kinding Njabi parasite showed that stool-derived miracidia were compatible only with B. forskalii, the exclusive host for S. intercalatum in Cameroon. Urine-derived miracidia were compatible only with B. truncatus, a S. haematobium host in Cameroon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928568 TI - Control of schistosome-transmitting snails in Kenya by the North American crayfish Procambarus clarkii. AB - Snail-transmitted trematode parasites such as schistosomes and liver flukes assume considerable medical and veterinary significance in tropical Africa. We have observed a strong negative association between the presence of medically important pulmonate snails and the crayfish Procambarus clarkii in freshwater habitats in Kenya. This crayfish, introduced into Kenya around 1970, readily consumes these snails in the laboratory. Field enclosure experiments indicate that crayfish exert a significant negative impact on the abundance of Biomphalaria pfeifferi, the intermediate host of the human blood fluke Schistosoma mansoni. It is likely that P. clarkii will continue to spread naturally in Kenya and that schistosome-transmitting snails will be excluded or reduced in numbers where crayfish are present. Procambarus clarkii may represent an alternative, biological means of snail control in East Africa. PMID- 1928569 TI - Comparison of the therapeutic efficacy and side effects of a single dose of levo praziquantel with mixed isomer praziquantel in 278 cases of schistosomiasis japonica. AB - A randomized double-blind study comparing the therapeutic efficacy of single dose of levo-praziquantel and mixed isomer praziquantel was carried out on 139 matched pairs of patients with schistosomiasis japonica. A single dose of either levo praziquantel (20 mg/kg) or praziquantel (40 mg/kg) was given to each patient. Four and six months after treatment, the stool ova negative conversion rates were 94.85% and 96.27% for the levo-praziquantel group, and 97.06% and 94.03% for the praziquantel group, respectively; there was no statistically significant difference between the two treatments (P greater than 0.05). For lightly and moderately infected patients, a single 20 mg/kg dose of levo-praziquantel was as efficacious as 40 mg/kg of praziquantel. Moreover, levo-praziquantel produced fewer side effects than praziquantel. These results suggest that levo praziquantel is the component of the mixed isomer preparation that is antihelminthic. Levo-praziquantel could be used therapeutically at half the current dose of the mixed isomer drug. PMID- 1928570 TI - Serologic and ultrasonographic parameters of praziquantel treatment of hepatic fibrosis in Schistosoma japonicum infection. AB - We describe the parameters useful in evaluating the development of hepatic fibrosis in Schistosoma japonicum infection, as well as its improvement after treatment with praziquantel (PZQ). Various serologic parameters and ultrasonographic images were examined, and their changes were monitored using rabbits infected with 200 or 300 cercariae of S. japonicum. Infected rabbits were administered one oral treatment of PZQ at a dosage of 100 mg/kg at 6, 12, or 24 weeks after infection. Histopathologic examinations revealed that PZQ had a strong and rapid effect, even on damage that developed long after the infection. The improvement of moderate hepatic fibrosis that developed over 24 weeks after infection was also detected by histopathologic examinations. The serum level of total bile acid was the most sensitive parameter in evaluating the severity of hepatic fibrosis and its improvement after treatment with PZQ. The level of serum procollagen-III-peptide was also useful in evaluating the development of hepatic fibrosis, but not in its improvement. Ultrasonography revealed specific echogenic bands and nodules according to the progress of granuloma formation and fibrosis, and the reversal of these changes could also be observed after treatment with PZQ. PMID- 1928571 TI - Association of the therapeutic activity of praziquantel with the reversal of Symmers' fibrosis induced by Schistosoma mansoni. AB - The impact of antischistosomal chemotherapy on the most important complication of intestinal schistosomiasis, Symmers' periportal fibrosis, has not been determined. Since abdominal ultrasonography has proven to be an effective tool in assessing the extent of Symmers' fibrosis in patients, we monitored the effect of chemotherapy, which involved the annual administration of praziquantel, on 48 Sudanese villagers having varying degrees of Symmers' fibrosis. Results indicate no significant differences in the fibrotic status of the 48 patients between 1986 and 1987, but test statistics (both the Wilcoxon signed rank test and Friedman's block/treatment test), indicated a significant decrease between the fibrotic status of the patients in 1986 and their fibrotic status in 1988 and 1989. Thus, after three years of therapy, 12 of the 48 patients no longer had detectable Symmers' fibrosis, while another 16 patients experienced a reduction in the amount of fibrosis in their livers. When coupled with our previous study, which demonstrated that annual treatment of children with praziquantel prevents the appearance of Symmers' fibrosis, it now appears that praziquantel may reverse this schistosomal-induced pathology. PMID- 1928572 TI - California serogroup viruses from mosquitoes collected in the USSR. AB - Four California serogroup viruses isolated from mosquitoes in the USSR were tested for antigenic analogy with prototype viruses of the California serogroup. The topotype isolates are biologically similar to, but antigenically different from each other. One is a subtype of snowshoe hare virus, two are different subtypes of Tahyna, Lumbo, and snowshoe hare viruses, and one is identical to Inkoo virus, previously isolated only in Finland. The results indicate that molecular studies of these viruses are necessary to comprehend their evolution. PMID- 1928573 TI - California serogroup virus infections in the Ryazan region of the USSR. AB - Serum samples from 60 people diagnosed in the summer of 1989 as having acute respiratory infections, meningitis or meningoencephalitis, acute pneumonia, Lyme disease, or other illnesses were tested by neutralization and hemagglutination inhibition with Tahyna, Inkoo, and snowshoe hare viruses of the California serogroup (family Bunyaviridae, genus Bunyavirus). Demonstration of a diagnostic increase in antibody titers between paired serum samples from seven people showed that their illnesses were probably caused by Inkoo or Tahyna viruses. The clinical pictures were less specific. One patient had signs of meningoencephalitis, three had signs of meningitis, and three had influenza-like illnesses. These observations and other results suggest that California serogroup viruses are widespread in Russia and may account for an unexpectedly large number of presently undiagnosed febrile illnesses, some with central nervous system involvement. PMID- 1928574 TI - A serologic study of California serogroup bunyaviruses in Sri Lanka. AB - A seroepidemiologic study of California (CAL) serogroup viruses (genus bunyavirus, family Bunyaviridae) was carried out on 952 human and 1,834 animal sera collected from different ecological zones of Sri Lanka (latitudes 5-10 degrees N, longitudes 79-82 degrees E). The sera were screened for neutralizing antibody to Lumbo (LUM), snowshoe hare (SSH), and trivittatus (TVT) viruses by plaque neutralization tests on Vero cells. Of 2,786 sera screened, 262 (9.5%) had antibody to one or more viruses Twenty-two sera, selected to represent different species of origin and reaction profiles, were titrated against nine CAL viruses: LUM, SSH, TVT, Tahyna (TAH), California encephalitis (CE), La Crosse (LAC), Inkoo (INK), Melao (MEL), and Guaroa (GRO). Results suggested that there were multiple CAL viruses active in Sri Lanka, one or more of them closely related to LUMBO and SSH viruses, and another related to MELAO virus. These viruses were active in both the wet and dry zones of the country, and infected humans as well as a range of domestic livestock. PMID- 1928575 TI - An alga-like organism associated with an outbreak of prolonged diarrhea among foreigners in Nepal. AB - An unidentified organism was found in the stools of 55 immunocompetent patients who presented to the CIWEC Clinic in Kathmandu, Nepal between June and November 1989. The microscopic features of the organism share characteristics of both coccidia and cyanobacteria species. From June 26, 1989 to November 17, 1989, 55 persons were identified as having the organism in at least one stool sample. The illness was characterized by prolonged watery diarrhea, anorexia, fatigue, and weight loss. The mean +/- SD duration of illness was 43 +/- 24 days (range 4 107). Thirty-four patients received a total of 78 courses of antimicrobial treatment (2.3 courses/patient). The mean +/- SD duration of illness in 34 treated patients was 46 +/- 24 days. In 14 untreated patients, the mean +/- SD duration of illness was 35 +/- 23 days. The organism is 8.0-9.0 microns in diameter, floats in Sheather's solution, and stains red with the modified acid fast stain. Since the agent was closely associated with a prolonged, self-limited diarrheal illness, it could easily have been misdiagnosed as Cryptosporidium. The organism should be looked for in the stools of patients with persistent diarrhea and a history of foreign travel. PMID- 1928576 TI - Zygomycosis mimicking paranasal malignancy. AB - A case of zygomycosis involving the maxillary sinus in a normal host and mimicking paranasal malignancy is presented. Computed tomographic images showing destruction of adjoining bony structures and histologic features of fungi are described and presented. A successful outcome was achieved with amphotericin B irrigation and parenteral amphotericin B. Nasal biopsy should be advised by both radiologists and clinicians in all cases of lesions that look like malignancy in the sinus areas before a treatment modality is initiated. PMID- 1928577 TI - Program and abstracts of the 40th annual meeting of the American Society of Tropical Medicine and Hygiene. Boston, Massachusetts December 1-5, 1991. PMID- 1928578 TI - Concealed progress in the management of severe surgical infection. PMID- 1928579 TI - Breast cancer in women under 35 years of age. AB - A review was undertaken of 226 patients with primary breast carcinoma who were 35 years of age, or younger, from 1960 to 1987. Comparisons to other studies of young and older women were made for clinical, pathologic, and survival characteristics. Young patients with breast cancer share many of the same disease characteristics of tumor type, location, size, and nodal involvement as their older counterparts. Five- and 10-year survival rates were comparable for patients with stage I or stage II disease and negative axillary lymph nodes. However, patients with stage II disease and positive nodes appear to have a decreased survival compared with older patients. PMID- 1928580 TI - Axillary node dissection in malignant melanoma. AB - Axillary node dissection was performed in 212 patients with malignant melanoma. For 212 initial dissections plus 49 repeat procedures (261 operations), wound infection occurred in 25 (10%) and arm edema in 10 (4%), with other complications being infrequent. The arm edema resolved promptly and completely six (2%) patients after elevation of the arm, while four (2%) patients have had permanent, moderate edema. The estimated 5-year survival rate for patients with clinically and histologically negative nodes was 74%. Among those with histologically positive nodes, when the nodes were not palpable, this rate was 73%; when the nodes were palpable and less than 2 cm in diameter, it was 46%; when they were palpable and 2 to 4 cm in diameter, it was 22%; when the nodes were larger than 4 cm in diameter, it was 18%; and when the nodes were fixed, it was 13%. The 5-year survival rate for 17 patients with positive nodes above the level of the axillary vein was 18%; 1 of 6 patients with resection of the axillary vein due to involvement is disease-free 57 months later. In patients who developed recurrence, further resection when feasible resulted in 13% of these patients being disease-free 5 years after the original axillary dissection. PMID- 1928581 TI - A prospective clinicopathologic study of venous invasion in colorectal cancer. AB - We performed a long-term prospective study on venous invasion of colorectal cancer. The degree of venous invasion was divided into four stages (V0 through V3). Venous invasion was classified into three types by location (Vx, Vy, and Vz). Hepatic metastasis occurred in 27%, 33%, and 20% of patients with V2, V3, and Vz tumors, respectively. Local recurrence occurred in 33% and 15% of the V3 and Vz groups, respectively. However, there were no significant differences among the groups in terms of the rate of pulmonary metastasis. The 6-year survival rate for Dukes' stage B tumors was 94%, 88%, and 74% in the V0, V1, and V2 groups, respectively. There was a significant difference in the survival rate between patients with V0 tumors and V2 and V3 tumors. However, no significant difference was noted in the location. In Dukes' stage C tumors, on the other hand, the survival rate was 77%, 56%, and 44% in the V1, V2, and V3 groups, respectively. Also, it was 85%, 73%, and 45% in Vx, Vy, and Vz cases, respectively. Significant differences were noted between V1 and V3 (or V2), and between Vz and Vx (or Vy). It appears that the degree and location of venous invasion influence not only hepatic metastasis, local recurrence, and survival rates but also have prognostic value. PMID- 1928582 TI - Unreliability of standard quantitative criteria in diagnostic peritoneal lavage performed for suspected penetrating abdominal stab wounds. AB - Thirty-five patients with abdominal stab wounds in whom clinical examination was equivocal on 2 separate occasions underwent diagnostic peritoneal lavage (DPL) prior to laparotomy. The red and white blood cell counts (cells/mm3) of the lavage effluent were compared with the operative findings. There were 26 positive and 9 unnecessary laparotomies, the latter consisting of 4 negative and 5 non therapeutic operations. Use of the standard quantitative criteria for red cells in DPL failed to identify significant injury in eight patients (31%), while the standard white cell count missed six injuries (23%). Their combined use resulted in three missed injuries (12%). Two false-positive results occurred using the red cell count alone and four using the white cell count alone, producing a combined false-positive result in four patients (11%). Reducing the cell threshold level to exclude missed injuries would increase dramatically the rate of unnecessary laparotomies. Although the standard quantitative criteria for DPL are superior to clinical assessment in patients with equivocal findings, their use in penetrating trauma does not achieve the same diagnostic accuracy as in blunt abdominal trauma. PMID- 1928583 TI - Effect of intraperitoneal administration of oxygen on the course of experimentally induced peritonitis. AB - Over the first 3 days of experimentally induced peritonitis, 40 rabbits were given oxygen intraperitoneally (IP) up to a pressure of 3 to 5 mm Hg in the peritoneal cavity at 12-hour intervals. Compared with a control group, significant differences were recorded in the mortality rate within the studied 7 day period of peritonitis (p less than 0.05). In 29 rabbits with intraperitoneal administration of oxygen, the size of the area that formed the inner wall of the abscess cavity was significantly smaller (p less than 0.01) on day 7 of peritonitis than in the control group. The number of samples obtained from the abscesses positive for Clostridium perfringens (p less than 0.05) and for Staphylococcus aureus (p less than 0.001) was significantly lower in rabbits that had received intraperitoneal oxygen than in the control group. The number of samples from the abscesses positive for Escherichia coli and Streptococcus faecalis was significantly lower in the control group than in the group with intraperitoneal administration of oxygen (p less than 0.05). These results indicate that intraperitoneal administration of oxygen has an effect on the mortality rate associated with peritonitis, the size of the intraperitoneal abscess, and the bacterial composition of these abscesses. PMID- 1928585 TI - General surgical problems requiring operation in postoperative vascular surgery patients. AB - Surgical intervention after vascular surgery usually occurs as a result of bleeding or thrombosis, whereas general surgical problems requiring operation after vascular surgery are unusual. The purpose of this study was to review the results of operations for general surgical problems done soon after major vascular surgery. From January 1985 to December 1989, 1,236 major vascular procedures were performed, and 15 patients developed significant postoperative general surgical problems including perforated duodenal ulcer (2), perforated diverticular disease (2), evisceration and dehiscence (2), liver infarct (1), gangrenous cholecystitis (2), clostridial myonecrosis (1), pseudomembranous colitis (1), and small bowel obstruction (4). The overall mortality was very high (47%), and the chance of dying was significantly higher (p less than 0.05) if the initial vascular procedure was an emergency (100% mortality). All the patients who died (n = 7) succumbed to sepsis. There was a long delay in diagnosis in all groups; however, the delay did not correlate with mortality. Although this is a study of a small group of patients with a very heterogenous group of complications, several observations can be made: (1) a general surgical problem after vascular surgery carries a very high mortality; (2) general surgical complications in postoperative vascular patients in whom the initial procedure was an emergency are very poorly tolerated and almost uniformly lethal; and (3) these elderly patients have multiple medical problems and seem unlikely to tolerate any septic insult. PMID- 1928584 TI - Results of radical radiotherapy for inflammatory breast cancer. AB - We performed a retrospective review of 65 patients with nonmetastatic clinical inflammatory breast carcinoma treated with radical radiotherapy as the sole local treatment between 1968 and 1986. Chemotherapy was given to 47 patients (72%). The median total radiation dose to the target volume was 6,984 cGy. With a median follow-up in survivors of 41 months, the 5-year actuarial probability of relapse free survival was 17% and the overall survival was 28%. Thirty patients experienced failure in the treated breast, skin, or draining lymph nodes, for a crude, uncensored local recurrence rate of 46%. Of the factors analyzed, only the response to initial chemotherapy was predictive of local recurrence. Local recurrence was noted in 0 of 3 patients with a complete response (CR) to initial chemotherapy, 5 of 17 patients with a partial response (PR), and 12 of 17 patients with less than a partial response (CR/PR versus less than PR, p = 0.009). We conclude that conventional radical radiotherapy in unselected patients is insufficient to manage the local tumor burden presented by inflammatory breast cancer, even when high doses are employed. PMID- 1928586 TI - Alterations in gastrointestinal motility during postoperative acute corticosteroid withdrawal. AB - Patients receiving exogenous corticosteroids may develop iatrogenic adrenal insufficiency, with resultant nausea, emesis, and abdominal distension if perioperative "stress steroid" dosages are inadequate. To investigate these gastrointestinal disturbances, motility measurements were obtained using perfused catheters in 10 dogs before steroid treatment (control), during administration of high-dose corticosteroids, and daily during 5 days of abrupt withdrawal. Withdrawal was characterized by a significant disruption in normal antral, duodenal, and jejunal motility with a prolongation of the migrating motor complex (MMC) and phases I and II, but not III (I = quiescence, II = irregular activity, and III = regular activity). Retrograde giant contractions (RGCs), giant migrating contractions (GMCs), and/or "intestinal fibrillation" were also observed during the first two withdrawal days. Adrenal weights and morphology did not change. We conclude: (1) high-dose corticosteroids can induce profound adrenal suppression in dogs without morphologic changes within 3 weeks; (2) high dose steroid administration enhances gastrointestinal motility; and (3) acute withdrawal causes disappearance or shortening of MMC and the development of RGCs and GMCs with associated emesis. PMID- 1928588 TI - Slit mesh for hernia repair. AB - A precise method of placing synthetic material during inguinal hernia repair is described. The material is slit at the inferior position to the internal ring so that its continuity is least compromised. PMID- 1928587 TI - Stapled or manual suturing in esophagojejunostomy after total gastrectomy: a comparison of outcome in 379 patients. AB - From January 1983 to December 1989, we performed esophagojejunostomy on 379 patients who underwent total gastrectomy for gastric cancer. A mechanical EEA stapler or conventional manual suturing was used. The clinical outcomes of 199 patients in whom stapling was used (stapler group) and 180 patients in whom manual suturing was done (manual group) were compared. Two of the 199 patients in the stapler group and 3 of the 180 patients in the manual group died of causes directly related to the anastomosis. In the stapler group, 16 stapled anastomoses were formed supradiaphragmatically, and manual suturing was done for 6 patients. The highly placed anastomosis was formed without left thoracotomy or with median sternotomy in 8 of the 16 patients in whom the stapling device was used and in 1 of the 6 patients in whom manual suturing was used. The incidence of anastomotic leakage and stenosis did not differ between the groups. Thus, the mechanical stapler facilitated the construction of a rapid, reliable esophagojejunostomic anastomosis. PMID- 1928589 TI - Arterial reconstruction of the pancreatic allograft for transplantation. AB - The shortage of organs is particularly acute in whole pancreas transplantation, because the liver and pancreas often share a common arterial supply, making combined procurement of both organs difficult. A previously described technique of simultaneous whole liver and pancreas procurement depended on "classic" hepatic arterial anatomy, which is present just over half the time. We describe herein our experience with three Y-reconstructions of the splenic and superior mesenteric arteries of the pancreatic allograft using donor allograft internal and external iliac arteries. In situ Doppler ultrasound examination of the pancreatic allograft after surgery demonstrated a patent reconstruction without evidence of stenosis or turbulent flow patterns. We believe this reconstruction is a safe, alternative method to provide arterial flow to the whole donor pancreas. PMID- 1928590 TI - Complications of dialysis access: a six-year study. PMID- 1928592 TI - A model for the assessment of students' physician-patient interaction skills on the surgical clerkship. AB - Physician-patient interaction skills are predominantly taught by successful role modeling but are rarely evaluated formally and systematically. This study describes a new model for the assessment of student physician-patient interaction skills and reports results of use in 78 third-year medical students on clerkships at two institutions. A single nurse instructor at each institution evaluated these skills using an 18-item checklist during student performance of wound care and dressing changes. Students were focused on the evaluation of their technical skills and were unaware of the evaluation of their interaction skills. Immediate feedback on performance was provided. The mean percentage score for the interaction skills was 35%, and no improvement was noted with greater clinical experience (later rotations). We conclude that there is a striking deficiency in physician-patient interaction skills among third-year students. The model described is effective for both evaluation and feedback. PMID- 1928591 TI - Effects of glucose on circulating and ileal intraluminal peptide YY and pancreatic polypeptide release. AB - Peptide YY (PYY) and pancreatic polypeptide (PP) are related hormones released systemically after a meal. The effects of glucose stimulation and vagal involvement on circulating and ileal luminal PYY and PP concentrations were evaluated in awake dogs. An oral glucose tolerance test (OGTT), intravenous glucose tolerance test (IVGT), 2-deoxyglucose bolus (2-DG), or atropine pretreatment prior to OGTT were administered to awake dogs with 25-cm ileal Thiry Vella fistulas. Circulating and ileal intraluminal PYY and PP levels were measured by radioimmunoassay. No changes were noted in circulating PYY, and circulating PP increased (p less than 0.05) only after administration of 2-DG. Ileal luminal PP recovery was minimal (less than 60 pg/mL) and was unchanged after all tests. Ileal luminal PYY recovery increased significantly after both OGTT and IVGT. Pretreatment with atropine abolished the luminal PYY response to OGTT, and 2-DG did not affect luminal PYY recovery. Blood glucose and insulin levels were similar in all groups. Peripheral cholinergic control of luminal PYY release is suggested by our findings, whereas a central mediation of circulatory PP release is supported by 2-DG stimulation. PMID- 1928593 TI - Proliferative pancreatic cysts: pathogenesis and treatment options. AB - Proliferative pancreatic cysts are subdivided into microcystic and mucinous cystadenomas. These rare, slow-growing, multilocular lesions usually remain localized for long periods of time, therefore frequently becoming rather sizeable before becoming symptomatic. Patients present with intermittent abdominal or back pain, nausea and vomiting, early satiety, and a palpable mass without a history of trauma or alcoholism. Computed tomographic scanning is the most useful laboratory test. The lesions are more often found in women, with the microcystic adenomas usually located in the head of the pancreas and the mucinous lesions in the pancreatic body or tail. At surgery, if it is at all possible, the lesions should be completely removed, even if it means performance of a Whipple procedure. This is particularly important for mucinous cysts because of their potential for malignant degeneration. Internal drainage or marsupialization procedures should not be done in these patients. The long-term results are excellent if the entire lesion is removed. PMID- 1928594 TI - Comparison of portal vein chemotherapy with hepatic artery chemotherapy in the treatment of liver micrometastases. PMID- 1928595 TI - Surgery interns' experience with surgical procedures as medical students. PMID- 1928596 TI - Implantation metastasis as a cause of local recurrence of colorectal carcinoma. PMID- 1928597 TI - Effect of 5-fluorouracil in cholesteatoma development in an animal model. AB - This investigation was designed to evaluate the effects of the antimetabolite 5 fluorouracil (5-FU) on cholesteatoma formation in a chinchilla model. The animals received middle ear applications of propylene glycol according to a procedure previously shown to produce cholesteatomas in 60% to 70% of animals. A 5% solution of 5-FU was then applied to the lateral surface of the tympanic membrane (TM) and, after 1 month, temporal bones were taken for histologic study. No macroscopically visible cholesteatomas were present in any of the 16 temporal bones included in the study. However, microscopic invasion of epidermis to the medial side of the TM was observed in four specimens; perforations were present in three of these. Although there was considerable variability in the response to 5-FU application, the majority of specimens showed little or no proliferation of connective tissue in the lamina propria of the TM. In the four specimens in which epidermis reached the medial side of the TM, it did so either by migration through microscopic breaks in the fibrous layer or via TM perforations. Thus, 5 FU did not completely inhibit migration of epidermis into the middle ear. However, the results of this study indicate that it does tend to reduce the proliferation of TM epidermis and connective tissue, thereby reducing the likelihood of cholesteatoma formation in the experimental model. PMID- 1928598 TI - Three-dimensional magnetic resonance imaging in skull base lesions. AB - Three-dimensional (3D) magnetic resonance (MR) imaging is a new digital technique developed 2 years ago by a multidisciplinary group of head and neck surgeons, clinical radiologists, and mathematicians at the University of Munich. In this study, the clinical value of this method, which has been improved significantly during the last 9 months, is evaluated in lesions of the skull base. Our results indicate that 3D reconstruction based on two-dimensional (2D) MR images reveals topographic details of interesting structures. In addition, this method offers new possibilities for the preoperative planning of tumor resection, particularly in lesions close to the skull base. However, this imaging technique will have to be improved before it achieves widespread clinical use. PMID- 1928599 TI - Rhabdomyosarcoma of the infratemporal fossa: diagnostic dilemmas and surgical management. AB - We present a rare case of embryonal rhabdomyosarcoma in the infratemporal fossa presenting as an atypical facial pain syndrome. Radiographic imaging of the patient is discussed, and magnetic resonance imaging is recommended as the diagnostic modality of choice when mass lesions of the infratemporal fossa are suspected. Finally, a temporal approach to the infratemporal fossa is described, along with its advantages as an application for tumor resection in this anatomic region. PMID- 1928600 TI - Immunoglobulin-coated bacteria in effusions from secretory and chronic suppurative otitis media. AB - Samples of middle ear effusions from 10 children with secretory otitis media and from 10 children with chronic suppurative otitis media were subjected to qualitative and quantitative bacteriologic analysis. In addition, secretory immunoglobulin A (SlgA)- and IgG-coated bacteria were evaluated using the immunofluorescence technique. Secretory otitis media effusions harbored few, if any, immunoglobulin-coated bacteria, whereas chronic otitis media effusions as a rule had heavily IgG- and SlgA-coated bacteria. However, those chronic otitis media effusions that were culture positive for Pseudomonas aeruginosa had no immunoglobulin-coated bacteria. The effusions of very young children were completely devoid of SlgA-coated bacteria. This study demonstrates that, based on the immunoglobulin coating of bacteria obtained from the middle ear cleft, one can evaluate immunologic response during otitis media. PMID- 1928601 TI - Voice prognosis after liquid and solid silicone injection. AB - A study was undertaken to determine the voice prognosis in 51 of the 408 patients with unilateral recurrent laryngeal nerve paralysis who had visited the Department of Ear, Nose and Throat at Keio University between 1977 and 1984. The 51 patients were divided into three groups: 18 patients without silicone injection, 15 with a silicone liquid implant, and 18 with a silicone solid implant. Data are provided to show that (1) both types of silicone implant are tolerated by the body and effective in improving voice and that (2) the liquid implant is ultimately absorbed and therefore useful for temporary voice improvement in patients in whom the prognosis for vocal fold paralysis is not known, whereas the solid implant is not absorbed and is therefore effective in the long term when recovery can be ruled out. PMID- 1928602 TI - Complications of adenotonsillectomy in children under 3 years of age. AB - Adenotonsillectomy in children may be performed safely on an outpatient basis in the majority of cases without an increase in complication rates. However, very young children comprise a unique patient subpopulation with regard to adenotonsillar surgery. Surgical indications in older children tend to be dominated by chronic recurrent infections, whereas younger children usually require surgery for chronic upper airway obstruction related to adenotonsillar hypertrophy. This study was undertaken to evaluate the adenotonsillectomy patient population under 3 years of age. Complication rates related to airway problems, hemorrhage, and dehydration were determined. Children under 3 years of age demonstrated an increased incidence of postoperative airway complications, manifested by oxygen desaturation and transient upper airway obstruction. It is recommended that adenotonsillectomy be performed on such patients on an inpatient basis with close postoperative monitoring including pulse oximetry. PMID- 1928604 TI - Temporal bone histopathology: residents' quiz. Mondini congenital malformation. PMID- 1928603 TI - Clinical radiology quiz. Ethmoid sinusitis that lead to orbital and preseptal cellulitis. PMID- 1928605 TI - Specific learning disorders: the possible role of brain damage. AB - The causes of many of the more subtle disorders of cerebral function are often obscure. Are they due to impaired development of the brain or to damage to the brain? Particularly if there is no definite evidence of the latter, and when talking to parents, it is better to use such terms as "minimal cerebral dysfunction". However this must not lesson in any way the constant search for the etiology of these disorders. There is no doubt about their frequency, and in one form or another, about one in ten children have special educational needs. There is therefore a major medical contribution to be made to the problems of these children, especially in terms of prevention. A review of the literature shows, among other causes, how often episodes during pregnancy and birth can lead to learning problems during school life. In the future the development of new neuroradiological, and other techniques, will help to explain these common disabilities. PMID- 1928606 TI - Effects of prone and supine position on heart rate, respiratory rate and motor activity in fullterm newborn infants. AB - Polygraphic recordings were obtained for 24 normal full-term neonates on their 4th or 5th day of life. Thirteen of the infants were first fed, laid supine for 3 hours, fed again around noon and laid prone for 3 more hours. The other 11 were first laid prone and then supine. The awake state was observed more in the supine than the prone position (P less than 0.001). Wakefulness occurred at the expense of state 1 and/or state 2. The heart rate (HR) was higher in babies lying prone. It was also higher in the afternoon than in the morning. No such relationship was found for the respiratory rate (RR). There was higher average EMG activity during state 1 in the prone position. The cross-correlation between HR and EMG activity was positive during state 2, and states 4 and 5, regardless of the position. The cross-correlation between the RR and the EMG was usually negative in state 2, and in states 4 and 5, there being many exceptions. The cross-correlation between breathing and heart-beat was mostly negative during state 2, but it eventually became positive due to periodic breathing, central apnoeas with bradycardia, stretches, and crawling movements. PMID- 1928607 TI - Hypocarbia as a pathogenic factor in pontosubicular necrosis. AB - In neonates pontosubicular necrosis (PSN) is one of the patterns of acute brain injury, the sites of maximum damage being the basis pontis and the subiculum of the hippocampus. A retrospective clinical and pathological study was performed on 16 preterm and 2 term neonates with PSN and compared with 16 age-matched controls. The results indicated that hypocarbia of less than 20 mmHg was one of the important factors in the pathogenesis of PSN. PMID- 1928608 TI - Comparison of cellular sensitivity to UV killing with neuropsychological impairment in Cockayne syndrome patients. AB - We studied the neuropsychological function including mental status and motor development, and cellular susceptibility to UV killing in four Cockayne syndrome (CS), of whom three were classic form (type I) and one was congenital form (type II). The results showed that there was no correlation between the age at symptomatic onset of CS neurological disorders and the levels of cellular UV hypersensitivity and that neuropsychological impairment did not parallel cellular hypersensitivity to UV killing. It was suggested that the cellular UV hypersensitivity might not be the essential cause of neurodegeneration in CS. PMID- 1928609 TI - EEG findings in children and adolescents with mitochondrial encephalomyopathies: a study of 25 cases. AB - EEG was studied in 25 children and adolescents with mitochondrial encephalomyopathies, defined on the basis of clinical, biochemical and morphological criteria. Twenty cases conformed to well-known mitochondrial syndromes: Alpers syndrome [6], Leigh syndrome [2], MERRF (myoclonus epilepsy and ragged red fibers) syndrome [3], MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) syndrome [5] and Kearns-Sayre syndrome [4]. Many patients were followed for several years with repeated EEG. In all, 112 EEG records were included in the study. A common feature of all the mitochondrial encephalomyopathic syndromes was slowing of the alpha rhythm. Epileptic discharges were seen in most syndromes. In spite of the small number of cases in each group, in Alpers, MERRF and MELAS syndromes we found sequential EEG patterns which seemed to be typical of the respective syndromes. In contrast, in Kearns Sayre syndrome, a slow background rhythm was the only consistent finding. We conclude that EEG, especially repeated recordings, may be of help in the diagnostic evaluation of mitochondrial encephalomyopathies. PMID- 1928610 TI - Monitoring of concentrations of clobazam and norclobazam in serum and saliva of children with epilepsy. AB - Clobazam was added to the previous antiepileptic drug therapy of 90 children suffering from drug resistant epilepsy. Ten patients became seizure free, although four of these later developed tolerance. Thirty-three patients experienced a decrease in seizure frequency, and 24 of these, too, developed tolerance. Forty-four patients showed no change in seizure frequency, and three experienced an increase. The best results were experienced by patients with myoclonic seizures, whereas patients with complex partial seizures usually developed tolerance. The concentrations of clobazam and its active metabolite norclobazam were measured in 251 serum and 57 saliva samples. The group of seizure-free patients had the lowest clobazam and norclobazam concentrations; tolerance was associated with the highest concentrations. Beneficial side effects were associated with low, and adverse effects with high, concentrations of norclobazam. The concentrations of clobazam and norclobazam in saliva correlated with concentrations in serum. Monitoring of serum and salivary concentrations of clobazam and norclobazam is of limited value only, and no therapeutic target range can be given. PMID- 1928611 TI - Changes in motoneuron excitability during postnatal life in the mouse. AB - H-reflex recovery, H-amplitude and H/M ratio were recorded in 54 mice aged 3-12 weeks to study the motoneuron excitability and changes in it during various stages of development. The H-reflex recovery curve at 12 wk showed 3 phases: an early, relative facilitation (before 10 ms), an almost total inhibition at 10 ms and a rapid recovery thereafter. At 3 wk, however, there was only slow recovery after 10 ms and the H-reflex recovery was significantly low during the 40-100 ms period as compared to those in the other age groups, indicating that between 3 and 6 wk, there was a significant increase in the motoneuron excitability. The H reflex amplitude also showed a significant increase during the 3-6 wk period. However, the H/M ratio did not show any significant increase either during the 3 6 wk period or thereafter. It is concluded that the H-reflex recovery at 3 wk suggests hypoexcitability of the motoneurons, possibly due to immaturity. Since there was a significant increase in the H-reflex recovery during the 3-6 wk period without any parallel increase in the H/M ratio, it is concluded that presynaptic and polysynaptic mechanisms acting on the motoneurons develop during this period. The increase in the H-reflex amplitude is possibly due to the increase in the muscle mass. The H-reflex recovery pattern at 12 wk, without the phase of late inhibition observed in man, is suggestive of less supra-spinal control mechanisms acting upon the motoneurons. PMID- 1928612 TI - Colpocephaly in identical twins. AB - Colpocephaly is congenital disproportionately enlarged occipital horns of the lateral ventricles. It is easily recognized on computed tomography, magnetic resonance imaging or cerebral ultrasonography. The first report of colpocephaly in identical twins is presented. This is also the first reported instance of above normal intelligence occurring in conjunction with colpocephaly. The associated anomalies found as mirror images in these twins imply a genetic basis for their colpocephaly. PMID- 1928613 TI - Uncoupling of blood flow and oxygen metabolism in the cerebellum in type 3 Gaucher disease. AB - Cerebral blood flow and oxygen metabolism were measured in a fourteen-year-old girl with type 3 Gaucher disease by using positron emission tomography (PET). Cranial CT and MRI showed only mild brain atrophy. PET demonstrated uncoupling of cerebral blood flow and oxygen metabolism, that is, a mild increase of cerebral blood flow and a reduction of oxygen extraction fraction and cerebral metabolic rate of oxygen only in the cerebellum. Although the mechanism is unknown, the above finding may reflect the underlying pathogenesis of the disorder. PET seems to be more sensitive than CT and MRI in detecting some functional abnormalities in the affected structures. However, further investigations must be done before concluding that this finding is unique to type 3 Gaucher disease. PMID- 1928614 TI - Disseminated cerebral histiocytosis X responding to vinblastine therapy: a case report. AB - A case of intracranial histiocytosis X with multiple parenchymal brain lesions is described. Despite severe neuroradiological findings, and involvement of a node and vertebra on presentation, the child is doing well clinically, with outpatient chemotherapy, 36 months after diagnosis. The prognosis of cerebral involvement in such atypical cases should probably be reevaluated. Therapeutic problems are discussed. PMID- 1928615 TI - Circadian rhythm of regular spike-wave discharges in childhood absence epilepsy. AB - Four girls with childhood absence epilepsy with several seizures every day were investigated using an ambulatory cassette EEG. Recordings were started at about 6 pm, and were run continuously for about 22 hours. We studied only the regular and symmetrical 3 Hz spike-wave discharges of at least 5 seconds duration, which are quite similar to or identical with those found in the clinical seizures. Regular spike-wave discharges occurred frequently during wakefulness in 2 cases and during sleep in the other 2 cases: in the latter, they occurred rarely during wakefulness. During wakefulness, we did not find a special time zone in which regular spike-wave discharges were facilitated; during nocturnal sleep, however, they were concentrated in the last third. The rate of regular spike-wave discharges per hour was the highest during stage 1, low during stages 2 and REM, and zero during stage 3 + 4. Average duration of regular spike-wave discharges was the longest during wakefulness in most cases, and shortest during stage 2 in all the cases. PMID- 1928616 TI - Plasmacytoid monocytes in Jessner's lymphocytic infiltration of the skin. A valuable clue for the diagnosis. AB - Plasmacytoid monocytes (PCMs) are mononuclear cells of monocyte/macrophage origin with peculiar plasmacytoid features on electron microscopy. This cell type is largely unknown in dermatopathology, probably due to standard fixation procedures. The authors provide a detailed histopathologic, immunohistochemical, and electron-microscopic study of PCMs in Jessner's lymphocytic infiltration of the skin (LIS). PCMs occurred in 58% of all biopsy specimens from 75 patients with LIS in single or multiple clusters within the dermal infiltrates. Recognition of this cell type was important for differential diagnostic reasons because PCMs did not occur in polymorphic light eruption. In discoid lupus erythematosus, PCMs were present in only 7.3% of 110 biopsy specimens. PCMs are probably involved in the activation, proliferation, and differentiation of T lymphocytes. Their origin and function are discussed and a special role in the homing of lymphocytes into the skin is suggested. PMID- 1928617 TI - Nucleolar organizer regions in malignant melanoma and melanocytic nevi. Comparison of two counting methods. AB - Using a silver staining technique, we studied nucleolar organizer regions (AgNOR) in paraffin sections of junctional nevi, compound nevi, intradermal nevi, blue nevi, dysplastic nevi, Spitz nevi, lentigo maligna, malignant melanomas in nevus, superficial spreading melanomas, and nodular melanomas. Two methods of counting black dots within nuclei were employed. One method was to count the discrete black dots within the nuclei, including the tiny black dots seen within the nucleolus; the second method did not take into account the subsidiary cluster of tiny black dots seen within the nucleolus, instead treating these dots as a single structure. Whichever method we used, a significant difference was found between the pooled mean AgNOR numbers for benign and malignant lesions. We found an overlap, however, between benign, in particular Spitz and dysplastic nevi, and malignant lesions when considering individual counts of AgNOR using both methods. We conclude that studying AgNOR does not seem to be a useful technique to differentiate Spitz and dysplastic nevi from malignant melanomas. PMID- 1928618 TI - A clinical, histological, and immunohistochemical comparison of acrodermatitis chronica atrophicans and morphea. AB - We compared 19 patients with acrodermatitis chronica atrophicans (ACA), a dermatosis caused by Borrelia burgdorferi infection, and 40 patients with morphea, a disease of heterogeneous origin where a borrelia etiology has been suggested in some cases, both clinically and histologically to define the differences between these two dermatoses. Clinically, ACA involves acral body sites with lower temperatures, is seen mostly in elderly persons, and presents as a livid discoloration that is not sharply demarcated. Morphea can be localized in embryonal structures, affects any age and body site, and exhibits extension at the periphery of the lesions. Histologically, ACA shows atrophy of collagen and elastic tissue as well as hypertrophic basophilic elastic tissue; whereas in morphea, sclerosis and polarizing elastic tissue are prominent. Graft-versus-host like reactions may be present in both dermatoses. Immunohistochemical testing with different lymphocyte markers showed differences only in the expression of HLA-DR antigens. These conditions can be distinguished from each other on a clinical and histological basis in most cases. In 17% of morphea biopsy specimens, however, histological differentiation from ACA was not possible. Moreover, the histological pattern of morphea was not associated with a positive borrelia serology. PMID- 1928619 TI - Differential diagnosis of cutaneous large cell lymphomas using monoclonal antibodies reactive in paraffin-embedded skin biopsy specimens. AB - We studied a large panel of monoclonal antibodies reactive on routinely processed paraffin-embedded tissue to determine their sensitivity and specificity in the diagnosis of 35 primary cutaneous large cell lymphomas of B- (n = 14) and T-cell origin (n = 21). The findings show that differentiation between clinically relevant subgroups can be obtained by a small panel of antibodies including L26, MB2, LN1, MT1, UCHL1, and Ber-H2. Pitfalls in the use of the reagents are discussed. PMID- 1928620 TI - Myoepithelial differentiation in basal cell carcinoma. AB - Five cases of basal cell carcinomas (BCC) of the skin are described showing morphologic and immunohistochemical features of myoepithelial differentiation. Histologically, they were characterized by a dermal proliferation of tumor cells connected with the epidermis by areas showing the features of conventional BCC, with the deeper portions of the lesion showing a population of oval to spindle cells with eccentric nuclei and homogeneous, ground-glass, or hyaline eosinophilic cytoplasm characteristic of the so-called hyaline cell of myoepithelial tumors of salivary glands. Additionally, scattered cells showing a signet ring configuration were present, and in two cases, focal areas displaying chondromyxoid elements were also seen that appeared to merge imperceptibly with the surrounding spindle cell population. By immunohistochemistry, the tumor cells in the spindle cell component showed strong, diffuse positivity for CAM 5.2 and muscle specific actin, and variable expression of keratin AE1/AE3, vimentin, glial fibrillary acidic protein, and S-100 protein, these findings being consistent with the immunostaining pattern of myoepithelial cells and their neoplasms. A brief review of the literature on the topic is presented, along with a discussion of the possible pathogenesis of this process. PMID- 1928621 TI - Immunohistochemical localization of type I, III, IV, V, and VI collagens and laminin in neurofibroma and neurofibrosarcoma. AB - By using antibodies to type I, III, IV, V, and VI collagens and laminin, we examined the localization of interstitial collagens and basement membrane components with indirect immunofluorescence and immunoelectron microscopy (IEM). Furthermore, the morphological changes of these collagens in malignant transformation were investigated. In neurofibroma, IEM showed type I, III, and V collagens to be present diffusely on cross-striated collagen fibrils, whereas type VI collagen was present between the fibrils. Type IV collagen and laminin were observed to surround tumor cells. In neurofibrosarcoma, tumor collagen bundles that reacted with antibodies to type I, III, V, and VI collagens were irregularly arranged. Immunofluorescent deposits that reacted with anti-type IV collagen and anti-laminin antibodies were decreased in number, showing a thin and sparse arrangement. PMID- 1928622 TI - The presence of dysplastic nevus remnants in malignant melanomas. A population based study of 551 malignant melanomas. AB - We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi. PMID- 1928623 TI - Epidermotropic metastatic melanoma simulating multiple primary melanomas. AB - Epidermotropic metastatic melanoma is usually distinguished from primary melanoma by the limitation of the epidermal involvement of the metastasis to an area overlying the dermal tumor. We report a case demonstrating multiple epidermotropic melanoma metastases with more extensive epidermal involvement simulating primary melanoma that occurred 20 years after excision of the primary tumor. PMID- 1928624 TI - Giant fibromyxoid tumors of the adventitial dermis. Forme fruste of trichodiscoma? AB - A 36-year-old paraplegic man developed multiple giant fibromyxoid tumors surrounding a meningomyelocele scar that we believe are forme fruste of trichodiscomas. Histologic examination showed a papillated, slightly hyperplastic epidermis surrounding a delicate fibrovascular proliferation set in a stroma of loose fibrillar connective tissue and stellate fibroblasts. A melanocytic nevus was incorporated into one of the lesions. We believe that these giant lesions are connective tissue nevi of the adventitial dermis that comprise a new clinical variant of trichodiscoma. The potential significance of the relationship between these abortive trichodiscomas and abnormalities of the neural crest is discussed. PMID- 1928625 TI - Nodular cutaneous amyloidosis. AB - A nodular cutaneous amyloidosis biopsy specimen from a solitary nodule of a 75 year-old patient was characterized by amino terminal sequence analysis and was proved to be derived from immunoglobulin kIII light chain. Five years after the diagnosis of amyloidosis in the skin was made, a rectal biopsy demonstrated amyloid deposits in a blood vessel. It is suggested that nodular cutaneous amyloidosis is a slowly progressive systemic disease of the AL type, that manifest itself mainly in the skin. PMID- 1928626 TI - Transepidermal elimination in exogenous ochronosis. A report of two cases. AB - Exogenous ochronosis is caused by the long-term application of skin-lightening creams containing hydroquinone. This irreversible disfiguring cosmetic problem assumes epidemic proportions in South African blacks. Mild ochronosis is characterized clinically by coarsening and darkening of the skin; severe ochronosis, by coalescing, caviar-like black papules and atrophy. Histology shows ochronotic collagen fibers with eventual formation of ochronotic colloid milium. A variable cellular infiltrate, which may be granulomatous, is present. We describe two patients with severe exogenous ochronosis who developed superimposed papular lesions. Histology in both cases showed transfollicular elimination of ochronotic fibers. In one patient, gross epidermal hyperplasia, a dense lichenoid infiltrate, and partial destruction of ochronotic fibers accompanied the process of elimination (cell-rich type). In the other, concomitant epidermal hyperplasia and a cellular infiltrate were absent (cell-poor type). Further studies are needed to prove or disprove the existence of such a proposed subdivision. Transepidermal elimination in exogenous ochronosis has been mentioned in a previous report, but to our knowledge this is the first detailed documentation of this phenomenon. The clinical and histopathological spectrum of exogenous ochronosis is thus expanded. PMID- 1928627 TI - G.C. Bonomo and D. Cestoni. Discoverers of the parasitic origin of scabies. PMID- 1928628 TI - What is the ISSVD classification of vulvar nonneoplastic epithelial disorders and intraepithelial neoplasia? PMID- 1928630 TI - Melanocytes in clear cell acanthoma. PMID- 1928629 TI - Congenital rhabdomyomatous mesenchymal hamartoma. PMID- 1928631 TI - Hepatic, metabolic and toxic effects of ethanol: 1991 update. AB - Until two decades ago, dietary deficiencies were considered to be the only reason for alcoholics to develop liver disease. As the overall nutrition of the population improved, more emphasis was placed on secondary malnutrition and direct hepatotoxic effects of ethanol were established. Ethanol is hepatotoxic through redox changes produced by the NADH generated in its oxidation via the alcohol dehydrogenase pathway, which in turn affects the metabolism of lipids, carbohydrates, proteins, and purines. Ethanol is also oxidized in liver microsomes by an ethanol-inducible cytochrome P-450 (P-450IIE1) that contributes to ethanol metabolism and tolerance, and activates xenobiotics to toxic radicals thereby explaining increased vulnerability of the heavy drinker to industrial solvents, anesthetic agents, commonly prescribed drugs, over-the-counter analgesics, chemical carcinogens, and even nutritional factors such as vitamin A. In addition, ethanol depresses hepatic levels of vitamin A, even when administered with diets containing large amounts of the vitamin, reflecting, in part, accelerated microsomal degradation through newly discovered microsomal pathways of retinol metabolism, inducible by either ethanol or drug administration. The hepatic depletion of vitamin A is strikingly exacerbated when ethanol and other drugs were given together, mimicking a common clinical occurrence. Microsomal induction also results in increased production of acetaldehyde. Acetaldehyde, in turn, causes injury through the formation of protein adducts, resulting in antibody production, enzyme inactivation, decreased DNA repair, and alterations in microtubules, plasma membranes and mitochondria with a striking impairment of oxygen utilization. Acetaldehyde also causes glutathione depletion and lipid peroxidation, and stimulates hepatic collagen production by the vitamin A storing cells (lipocytes) and myofibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928632 TI - Diazepam preference in males with and without an alcoholic first-degree relative. AB - The relationship between family history of alcoholism and risk for benzodiazepine abuse was examined by assessing the reinforcing and subjective effects of diazepam (DZ; 4-28 mg) in 14 normal (i.e., nonalcoholic) males with a first degree alcoholic relative (family history positive; FHP) and in 13 control subjects without alcoholic relatives (FHN). Reinforcing effects were measured using a double-blind preference procedure in which subjects first sampled DZ and placebo (PL) and then chose the substance they preferred. Subjects were also allowed to select the dose of drug they preferred on each choice session. The subjective effects of DZ were assessed using standardized self-report questionnaires. Neither group chose the DZ more often than PL. The FHP group chose DZ slightly (but not significantly) more often than the FHN group (mean choices FHP 1.42 vs. FHN 1.15 out of 3 choice options), and they chose slightly (but not significantly) more doses of DZ within sessions (FHP 25 mg vs. FHN 18 mg). The groups did not differ in their responses to DZ on other measures (e.g., subjective drug effects or drug liking). To the extent that laboratory procedures such as the one used here provide a model for assessing the abuse liability of drugs, these results do not provide strong evidence that males with a family history of alcoholism have an elevated risk for developing benzodiazepine abuse or dependence. PMID- 1928633 TI - Alcohol-related efficiency deficits using an ecologically valid test. AB - This study investigated whether male and female alcoholics and controls differed in their ability to solve an ecologically valid measure of abstraction. Ninety one alcoholics (39 females, 52 males) and 61 community controls (36 females, 26 males) completed a battery of abstraction tasks including a Piagetian-type task, the Plant Task. The Plant Task demands that subjects predict the outcome of an unseen plant given a specific treatment regime. No group differences in the ability to correctly predict the unseen plant's outcome were obtained. Alcoholics were significantly poorer than controls in isolating the relevant variable (chi 2 (1) = 8.24, p = 0.004). There were no sex differences in the ability to isolate the relevant variable. However, there was a sex effect in the number of irrelevant explanations (chi 2 (3) = 15.58, p = 0.001) with females producing more than males and female alcoholics more than any of the other three cells. These data suggest that (1) alcoholics may exhibit subtle abstraction deficits most readily observed in tasks examining process as opposed to final performance, (2) males and females differ in their response patterns regarding irrelevant material, and (3) further empirical study of the Plant Task may support its use in experimental and clinical settings. PMID- 1928634 TI - Multimodality exploration of event-related potentials in chronic alcoholics. AB - Short- and long-latency auditory evoked potentials (SAEPs and LAEPs), visual evoked potentials (VEPs), and contingent negative variation (CNV) were studied in 32 chronic alcoholics and their age-, sex-, and education-matched control subjects. The alcoholics exhibited a delayed SAEP peak V and an increase in the III-V and I-V intervals, increased VEP P100 latency, increased LAEP N2 and P3 latencies and increased LAEP N1-P2 amplitude. The analysis of the anomalies at a clinical level indicates a differential sensitivity of the event-related potentials. The parameters most sensitive to chronic alcohol consumption were (in descending order) P3 latency, peak V latency, the I-V and III-V intervals, and P100 latency. PMID- 1928635 TI - Effects of alcoholism and instructional conditions on speed/accuracy tradeoffs. AB - The speed and accuracy of neuropsychological performance in alcoholics and nonalcoholics were assessed for each item within a four-test computerized battery. Subjects were randomly assigned to one of three instructional conditions: Speed-emphasis instructions, Accuracy-emphasis instructions, or Typical instructions emphasizing speed and accuracy equally. Across conditions, alcoholics were less accurate and took longer to perform than controls. Examining speed and accuracy components separately within each condition, as predicted, the greatest differences in accuracy scores between alcoholics and controls appeared in the Speed-emphasis condition, while the greatest group differences in speed scores appeared in the Accuracy-emphasis condition. The results indicate that the relationships between speed and accuracy are dissimilar between alcoholics and controls; alcoholics exhibit speed/accuracy tradeoffs in that they are unable to adjust performance to meet speed or accuracy demand without suffering substantial compromise in the other aspect of performance. These results have implications for future studies concerning methodological approaches to speed and accuracy assessment and provide support for an information-processing deficit associated with chronic alcohol abuse. PMID- 1928636 TI - Pharmacotherapies for alcoholism: promising agents and clinical issues. AB - The past 10 years have witnessed important advances in research on pharmacotherapy for alcoholism. Promising drugs are discussed under six headings: agents to treat alcohol withdrawal; anticraving agents; agents that make drinking an aversive experience; agents to alleviate concomitant psychiatric problems; agents to treat concurrent drug abuse; and amethystic ("sobering-up") agents. Research on the drug classes is summarized and clinical issues surrounding specific agents and alcoholism pharmacotherapy in general are discussed. Finally, long-range therapeutic implications of recent findings on the actions of alcohol on basic mechanisms of the brain are offered. PMID- 1928637 TI - Loss of control drinking among first offender drunk drivers. AB - A mathematical model of alcohol consumption, which characterizes individual drinking in terms of frequency of consumption and subsequent loss of control drinking once consumption has been initiated, is introduced. The model provides a conceptual link between behavioral indices of alcohol consumption patterns and theoretical models of the role of loss of control drinking in the genesis of alcohol dependence and alcoholism. Based on data from a large sample of first offender drunk drivers, it is shown that specific measures of consumption patterns can be used to provide individual estimates of parameters of the model. These estimates are shown to be strongly related to one measure of alcohol dependence and to introspective reports of loss of control drinking. PMID- 1928638 TI - Psychiatric symptoms in alcoholics attending outpatient treatment. AB - The importance of psychiatric symptomatology for the treatment course of alcoholics was analyzed in a long-term outpatient treatment study. Seventy-two patients, 60 men and 12 women, were personally interviewed during treatment and after 3 years. Before treatment psychiatric symptoms were rated according to the Comprehensive Psychopathological Rating Scale (CPRS). Women had significantly higher scores than men. Men with many symptoms and women had more psychological benefits from drinking and a more impaired personality structure than men with few symptoms. Men with many symptoms also had a lower level of social functioning. The severity of abuse did not differ between the three groups. Men with many symptoms had a less favorable outcome between 25 and 36 months after start of treatment than men with few symptoms and women. Among men who completed treatment, those with many symptoms showed a less successful course after 6 months and during the 3rd year after start of treatment, while differences after 3 months and during later stages of treatment were less pronounced. It is suggested that before start of treatment a psychiatric evaluation should be performed including psychiatric diagnosis, personality analysis, and an assessment of psychological benefits from drinking. PMID- 1928639 TI - Personality, alcohol consumption, and menstrual distress in young women. AB - There has been a longstanding hypothesis that some women develop alcohol dependence as a result of drinking to alleviate premenstrual dysphoria. This study investigated the relationship between personality factors, alcohol consumption, and menstrual distress symptoms in nonalcoholic drinking young women. Normally menstruating women monitored their alcohol intake and physical and affective distress symptoms daily for two consecutive menstrual cycles. Subjects were unaware that their menstrual cycles and symptoms were being monitored. Subjects also completed the Minnesota Multiphasic Personality Inventory (MMPI), the Eysenck Personality Questionnaire (EPQ), Cattel's Sixteen Personality Factor Questionnaire (16PF), and the Vando Reducer-Augmenter Scale. The MMPI scales were factor analyzed to reduce the number of variables. Four derived MMPI factors were added to the VANDO, the three EPQ factors, and the four higher order factors of the 16PF to provide a total of twelve personality predictors. Separate regression analyses were carried out between personality factors and both alcohol consumption and menstrual distress. The results revealed that the women who drank more tended to be significantly more extroverted, spontaneous, carefree, and open to change. By contrast, women who reported greater over-all menstrual distress tended to be less capable, secure, and well adjusted and reported a greater number of emotional and psychological problems. There was no correlation between alcohol consumption and menstrual distress. It was concluded that the results contradict the alcoholism-menstrual cycle hypothesis. PMID- 1928640 TI - Cognitive performance of alcoholics: a longitudinal evaluation of the role of drinking history, depression, liver function, nutrition, and family history. AB - To assess the role of drinking history, depression, liver function, nutrition, and family history on cognitive performance, 171 detoxified male alcoholics were administered a brief neuropsychological examination at admission and discharge from an inpatient treatment program and at a 3-month follow-up evaluation. Regression analyses showed that at admission, depression and liver function were significant predictors of neuropsychological performance, whereas at discharge 3 to 4 weeks later only age and an estimate of premorbid intelligence were significant predictors. At the 3-month follow-up, estimates of drinking following discharge and severity of depressive symptoms were major significant predictors of neuropsychological performance. Indices of drinking prior to admission to the treatment program, nutrition, and family history for alcoholism did not predict performance on any of the three test occasions. These findings indicate that in addition to the chronic neurotoxic effect of alcohol a number of different medical and psychiatric factors, as well as the acute effects of alcohol, contribute to the cognitive scores of patients at various points in the clinical course. PMID- 1928641 TI - Impulsivity, sensation seeking, and behavioral and emotional responses to alcohol. AB - Three hundred forty-two male and female subjects from the Colorado Alcohol Research on Twins and Adoptees returned a mailed questionnaire that included the Eysenck Impulsivity-Venturesomeness-Empathy scales. These subjects had previously been tested in a procedure in which they were given a 0.8 g/kg dose of ethanol to bring their peak blood alcohol concentration (BAC) to near 0.10 g/dl, given topping doses to maintain this BAC over a 3-hr period, and repeatedly tested on a battery of diverse physiological, psychomotor, perceptual speed, and mood measures. Impulsivity was significantly correlated with higher levels of self reported alcohol use and the occurrence of alcohol use problems in males, while both impulsivity and venturesomeness (sensation seeking) were significantly correlated with lessened motor impairment following alcohol use in males. These personality measures, however, were not significantly correlated with mood measures following initial alcohol dosing. Impulsivity and venturesomeness were uncorrelated with alcohol use and responses to alcohol in females, but as with males, impulsivity was related to the occurrence of alcohol use problems in females. PMID- 1928642 TI - Effect of ibuprofen on alcohol-induced teratogenesis in mice. AB - The purpose of the present study was to examine the effect of the prostaglandin synthetase inhibitor ibuprofen (IBU) on the teratogenic actions of alcohol. On day 10 of pregnancy, C57BL/6J mice were injected subcutaneously with 25 mg/kg IBU or vehicle control. One hour later, the mice were intubated with 5.8 g/kg alcohol or an isocaloric control solution. A group injected subcutaneously with 150 mg/kg aspirin, followed by 5.8 g/kg alcohol 1 hr later, served as a positive control. The results showed that maternal alcohol treatment resulted in significantly decreased fetal weight and an increased number of fetuses with limb and kidney defects. Implantation sites and prenatal mortality were not affected. IBU did not have any effect on these dependent variables. IBU statistically antagonized the teratogenic effects of alcohol on fetal weight and dysmorphology. These effects, however, were not as marked as in the Aspirin-Alcohol positive control group. These results are discussed in the context of clarifying the role of prostaglandins in the etiology of alcohol-induced birth defects. PMID- 1928643 TI - Effects of in utero ethanol exposure on the developing serotonergic system. AB - Previous work in this laboratory demonstrated that the 19- and 35-day-old offspring of ethanol-fed rats have a significant deficiency of cortical serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), as well as a decrease in the number of total 5-HT1 receptors in the motor and somatosensory cortex. The present studies extend our previous reports by demonstrating that there is also a deficit of 5-HT and 5-HIAA in the motor cortex but not in the somatosensory cortex. In addition, we have shown that a deficit of 5-HT1A receptors in the motor and somatosensory cortices contributes to the deficit of total 5-HT1 receptors. In contrast, we did not observe any changes in the binding to 5-HT1B receptors in these cortical regions from the 19-day-old offspring of ethanol-fed rats. The present studies also examined the effects of in utero ethanol exposure on the early development of the serotonergic system. The results of these studies demonstrated a deficit of 5-HT and/or 5-HIAA in the brain stem as early as the 15th day of gestation (G15) and in the cortex as early as G19. In addition, we demonstrated a delay in both the normal developmental decline of 5-HT1A receptors in the brain stem and in the acquisition of cortical 5-HT1A receptors. No changes were found in the binding of [125I]cyanopindolol to 5-HT1B receptors in either region of fetal or neonatal rats exposed to ethanol in utero.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928644 TI - Effects of alcohol on beta-endorphin and reproductive hormones in the male rat. AB - In an attempt to examine the relationship between alcohol-induced alterations in immunoreactive beta-endorphin (i-beta E) levels in the hypothalamic-pituitary gonadal axis and the synthesis and release of reproductive hormones, male rats were treated with either an acute intraperitoneal injection of alcohol or were chronically exposed to an alcohol-containing liquid diet. Hypothalamic, pituitary, serum, and testicular levels of immunoreactive beta-endorphin (i-beta E) and serum levels of luteinizing hormone (LH) and testosterone were measured at various times after initiation of these treatments. Testicular interstitial fluid (TIF) volumes and levels of TIF i-beta E and testosterone were also measured 4 hr after acute treatment as an index of testicular release of these substances. Acute alcohol decreased pituitary levels of i-beta E and increased serum levels of the peptide for up to 1 hr after its injection, but did not alter hypothalamic or testicular levels. Acute alcohol markedly increased TIF i-beta E and decreased TIF testosterone and TIF volume. Sharp decreases in serum LH and testosterone were observed in association with these acute changes in i-beta E levels in the pituitary, blood, and testes. During chronic alcohol exposure serum testosterone levels were substantially depressed, but tolerance appeared to develop quickly to the chronic effects of alcohol on serum LH. Similarly, tolerance to alcohol's effects on i-beta E levels in the pituitary and serum also appeared to develop during chronic alcohol administration. However, hypothalamic and testicular i beta E levels were markedly suppressed by chronic alcohol administration in contrast to the lack of effect observed after acute alcohol administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928646 TI - Differential effects of ethanol on punished responding in the P and NP rats. AB - The effects of ethanol administration (0, 0.25, 0.5, 0.75 and 1.0 g/kg intraperitoneal) were examined in a conflict test in 24 alcohol-preferring (P) rats, 17 alcohol-nonpreferring (NP)-rats, and 24 heterogeneous Wistar rats. The conflict test was a modified Geller-Seifter procedure employing an unpunished random interval 30-sec component and an incremental shock conflict component. Heterogeneous Wistar rats displayed significant increases in punished responding with doses of 0.5, 0.75, and 1.0 g/kg of ethanol. P-rats did not show a significant increase in punished responding until 0.75 g/kg ethanol. NP rats displayed significant increases in punished responding with all doses tested (0.25, 0.5, and 0.75 g/kg). There were no group differences in the effects of ethanol on unpunished responding. Thus NP-rats were more sensitive and P-rats were less sensitive to the anticonflict effects of ethanol than heterogeneous Wistar rats. The results suggest that the P and NP rats may show a profile of sensitivity to the anticonflict effects of ethanol similar to the sensitivity to the intoxicating effects of ethanol observed in family history positive and family history negative human subjects. PMID- 1928645 TI - Effects of short-term ethanol and nutrition on the hepatic microsomal monooxygenase system in a model utilizing total enteral nutrition in the rat. AB - The majority of studies examining the effects of ethanol on the hepatic microsomal monooxygenase system, (HMO), have utilized the liquid diet regimen of Lieber and DeCarli. While much has been learned with this useful model, there are some concerns associated with diminished nutrient intake. Decreased food intake in the presence of high levels of ethanol could give rise to at least three effects; primary ethanol effects, primary nutritional effects and/or effects resulting from interactions between nutritional deficiencies and ethanol (i.e., synergistic effects). A model similar to that developed by Tsukomoto and French is used in the current study, in which ethanol is infused directly into the stomach as part of a total enteral nutrition system (TEN). This assured that nutrients sufficient for normal growth were consumed. Two clinically relevant diets were selected for study. One diet is very similar to that used for intravenous feeding of human patients (diet A) and the other similar to that used for intragastric feeding of patients (diet B). The present study was conducted to determine the effects of different diets on HMO and to determine whether ethanol has demonstrable effects in the presence of dietary sources that promote normal growth rates. The effects of the two liquid diets alone or of TEN where 35% of the total calories in the diets were replaced by ethanol for 8 days were examined on HMO of adult male Sprague-Dawley rats. HMO substrates examined included testosterone, the alkoxyresorufins, carbon tetrachloride, and p-nitrophenol. Levels of cytochrome P-450 apoproteins were studied by Western blot analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928647 TI - Hormonal tolerance to ethanol is associated with decreased expression of the GTP binding protein, Gs alpha, and adenylyl cyclase activity in ethanol-treated LS mice. AB - Using the proopiomelanocortin (POMC) system as a marker, long sleep (LS) and short sleep (SS) lines of mice were investigated to explore the cellular events that occur during the acquisition of hormonal tolerance to ethanol. Four-day ethanol exposure (1.8 g/kg/24 hr) increased anterior pituitary POMC mRNA levels 4 fold in the LS line and 2-fold in the SS line. Following 7 days of ethanol exposure (1.8 g/kg/24 hr), anterior pituitary POMC levels returned to basal values in the LS line but remained elevated (2-fold) in the SS line. In this setting, the loss of ethanol's ability to sustain elevated POMC mRNA levels in the LS line is defined as hormonal tolerance. Since POMC biosynthesis is primarily regulated through adenylyl cyclase, ethanol-induced alterations in this signal transduction system were explored. Paralleling the effects of ethanol on POMC mRNA levels, ethanol exposure reduced GTP-gamma-S, AIF3-, and MnCl2 stimulated adenylyl cyclase activity by 35%, 21%, and 24%, respectively, in the LS line without effecting adenylyl cyclase activity in the SS line. To determine whether ethanol-induced changes in adenylyl cyclase activity in LS mice could result from alterations in G proteins, protein levels of G, alpha and Gi alpha were determined by western analysis before and after ethanol exposure. Paralleling the effect on POMC mRNA levels and adenylyl cyclase activity, ethanol induced a 35% reduction in Gs alpha protein levels in LS mice but did not alter Gi alpha levels. Neither Gs alpha nor Gi alpha levels were altered in the SS line.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928648 TI - Effects of prenatal ethanol exposure on glucocorticoid receptors in rat hippocampus. AB - Animals exposed to ethanol in utero are typically hyperresponsive to stressors in adulthood as indicated by increased adrenocortical activation and/or deficits in response inhibition or recovery following stress. In the present study we reasoned that a deficit in feedback control of pituitary-adrenal activity might underlie this hyperresponsiveness in fetal ethanol-exposed (FEE) animals. Further, we hypothesized that a long-term decrease in hippocampal glucocorticoid receptor concentration, induced by prenatal ethanol exposure, might mediate such a deficit in pituitary-adrenal feedback regulation. Male and female Sprague Dawley rats from prenatal ethanol (E), pair-fed (PF), and control (C) treatment groups were tested in adulthood for determination of cytosolic hippocampal glucocorticoid receptor binding. No significant differences in specific binding (Bmax) or binding affinity (Kd) of either type I or type II glucocorticoid receptors were found among animals from E, PF, and C conditions. There were, however, significant sex differences in receptor concentration and binding affinity; females showed significantly greater maximal binding and significantly lower binding affinity than males. These data do not support the hypothesis that prenatal ethanol exposure induces a long-term decrease in hippocampal glucocorticoid receptors in animals tested under basal nonstressed conditions. However, these data do not preclude the possibility that receptor binding capacity may be differentially affected in E, PF, and C animals during stress. PMID- 1928649 TI - The relationship between brain temperature during intoxication and ethanol sensitivity in LS and SS mice. AB - The present study characterized the relationship between brain temperature, rectal temperature, and ethanol sensitivity in the selectivity bred long-sleep (LS) and short-sleep (SS) mice. Radiotelemetric brain probe implanted and nonimplanted LS/lbg and SS/lbg male mice were injected with 2.5 and 4.9 g/kg ethanol, respectively, before exposure to ambient temperatures of 15 degrees C, 22 degrees C, or 34 degrees C. Ambient temperature significantly affected rectal temperature, brain temperature, and ethanol sensitivity, measured by impairment of righting reflex. Brain and rectal temperatures at return of righting reflex (RORR) were highly correlated. In SS mice brain and rectal temperatures at RORR were significantly positively correlated with loss of righting reflex (LORR) duration and significantly negatively correlated with blood ethanol concentration (BEC) at RORR. In LS mice rectal temperature at RORR was significantly negatively correlated with LORR duration, while both brain and rectal temperature at RORR were significantly positively correlated with BEC at RORR. The strength of the correlations and r2 values generated from linear regression analysis indicates that body temperature during intoxication can explain up to 52% of the variability in ethanol sensitivity in SS mice, but only 19% of the variability in ethanol sensitivity in LS mice. The correlational analyses are consistent with previous results based on comparisons between rectal temperature and ethanol sensitivity and extend to direct brain temperature measurement the evidence that decreasing temperature during intoxication decreases ethanol sensitivity in SS mice and increases ethanol sensitivity in LS mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928650 TI - Effect of chronic ethanol on apolipoprotein (Apo) E synthesis and glycosylation in rats. AB - We have previously shown in rats that chronic ethanol feeding significantly inhibits the incorporation of labeled leucine into Apo E secreted into the liver perfusate (p less than 0.01). Fish oil has been shown to counteract many of the adverse effects of ethanol. In order to explore whether this inhibitory effect of ethanol was due to the decreased synthesis and/or defective glycosylation of this glycoprotein, we have determined the effects of chronic ethanol and fish oil on the synthesis and glycosylation of Apo E in vivo. Four groups of male Wistar rats were pair-fed the following liquid diets for 8 weeks; (1) Ethanol Regular Fat, (2) Control Regular Fat, (3) Ethanol Fish Oil, and (4) Control Fish Oil. At the end, the rats were intraportally injected with a single dose of [U-14C]leucine (0.2 microCi/g body weight) and/or [2-3H]mannose (1 microCi/g body weight) and killed after 30 min. The incorporation of the labeled precursors into the immunoprecipitable Apo E was measured in the liver and its microsomal and Golgi fractions. The results showed marked decreases in mannose incorporation into total glycoproteins and specifically of Apo E in whole liver, microsomal, and Golgi fractions under ethanol treatment. In contrast, the leucine incorporation into liver Apo E increased 11% (p less than 0.048) by ethanol treatment. As a result, the [3H]mannose/[14C] leucine incorporation ratio also decreased 41% to 47% at the whole liver, microsomal, and Golgi fractions indicating a marked inhibition in glycosylation of Apo E in the ethanol group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928651 TI - The relationship between ethanol-induced hyperglycemia and hypothermia: evidence of genetic correlation. AB - The hyperglycemic and hypothermic responses to acute ethanol exposure (0, 2, 4, 6 g/kg, intraperitoneally) were examined in non-fasted mice selectively bred for sensitivity (COLD line) or insensitivity (HOT line) to ethanol-induced hypothermia. Blood samples and rectal temperatures were obtained immediately before injection and hourly for 4 hr after injection. As expected, COLD mice demonstrated greater and more prolonged reductions in body temperature than HOT mice, especially at the 4 g/kg dose (HOT: -2.58 degrees C, COLD: -5.08 degrees C). Ethanol produced significant dose-dependent elevations in blood glucose levels over the 4-hr sampling period in both lines. The greatest elevations in blood glucose levels were seen at 4 g/kg, with COLD mice (mean = 225.1 mg/dl) showing significantly greater elevations in blood glucose levels compared to HOT mice (mean = 177.0 mg/dl). These results support the hypothesis that the thermic and glycemic effects produced by ethanol are due to related neural processes that share a common genetic component. PMID- 1928652 TI - Effect of concentration of ingested ethanol on blood alcohol levels. AB - The effect of the concentration of ingested ethanol on the resulting blood alcohol concentrations (BAC) was tested in both humans and rats. In humans, when 0.3 g/kg body weight ethanol was ingested postprandially, the mean area under the blood alcohol curve (AUC) and the mean peak BAC were significantly lower with a concentrated (40% w/v) than with a dilute (4%) solution. Similarly, rats in the fed state exhibited decreasing mean AUCs with increasing concentrations (4%, 16%, and 40%) of intragastrically administered ethanol (1.0 g/kg). Pharmacokinetic analysis comparing intragastric and intraperitoneal administration of ethanol to rats indicated that the more concentrated solution resulted in less alcohol reaching the systemic circulation (4%: 0.896 +/- 0.074 g/kg: 16% 0.772 +/- 0.072 g/kg; 40%: 0.453 +/- 0.037 g/kg) and suggested that this affect could be attributed to two factors: increased gastric retention of ethanol (4%: 0.109 +/- 0.024 g/kg; 16%: 0.102 +/- 0.016 g/kg; 40%: 0.214 +/- 0.042 g/kg) and a large increase in first-pass metabolism (4%; 0.004 +/- 0.054 g/kg; 16%: 0.145 +/- 0.048 g/kg; 40%: 0.329 +/- 0.044 g/kg). In contrast to the results in the fed state, in humans fasted overnight the concentration of alcohol consumed (4%, 16%, and 40%) had no significant effect on mean AUCs. In fasted rats, mean AUCs after intragastric intubation of the two lower concentrations of ethanol (4% and 16%) were comparable to those found after intraperitoneal injection, and only the highest ethanol concentration (40%) produced a lower mean AUC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928653 TI - Electrophysiological response to ethanol in P and NP rats. AB - Event-related potentials (ERPs) have been successfully used in human subjects to evaluate alcoholics as well as those at risk for the future development of alcoholism. In the present study, two lines of rats, those with a preference for ethanol consumption (P) and those not preferring (NP) to drink ethanol were studied using ERP-producing stimuli. Rats were implanted with electrodes in the frontal cortex and dorsal hippocampus (DHPC). A passive auditory "oddball" paradigm was used to record ERP responses following saline and two doses (0.5, 1.0 g/kg) of ethanol. P and NP rats differed under the saline condition in that P rats had smaller N1-like ERP components and larger P2 waves in both cortex and hippocampus. P and NP rats were also found to differ in response to ethanol administration. NP rats evidenced dose-dependent reductions in ERP component amplitudes such as the N1 recorded from cortical sites. P rats did not have such reductions in N1 amplitudes and in fact, displayed increased N1 amplitudes in hippocampal sites. These studies provide further electrophysiological evidence that rats with a genetically influenced preference for ethanol consumption differ from nonpreferring rats at baseline and have a less intense depressant or more stimulating response to ethanol challenge. PMID- 1928654 TI - Ethanol influences class I and class II MHC antigen expression on human fetal islet-like cell clusters. AB - Several autoimmune diseases have been linked to an aberrant expression of major histocompatibility complex (MHC) products Ethanol enhances Class I and Class II products on a variety of cell types, and there is evidence for an autoimmune etiology in numerous pathologies associated with alcoholism. We examined whether ethanol alters the expression of Class I and Class II MHC products on human fetal islet-like cell clusters. Incubation of islet-like clusters for 48 hr in ethanol at a starting concentration of 1.5% increased the percentage of single cells expressing Class I. The percentage of cells expressing Class II did not change, but their relative mean fluorescence increased significantly. These findings suggest that alcohol ingestion could alter MHC expression on pancreatic islet cells in vivo perhaps affecting the development of diabetes in genetically predisposed individuals. These findings also support the hypothesis that the rising incidence of type 1 diabetes seen in areas of the world where the per capita consumption of alcohol is also increasing may be a consequence of the immunological effects of alcohol intake. PMID- 1928655 TI - Guidelines for the standardization of bronchial provocation tests with allergens. An update by an international committee. PMID- 1928656 TI - Passive smoking and childhood asthma. Urinary cotinine levels in children with asthma and in referents. AB - Passive exposure to tobacco smoke was assessed in children with asthma (age 3-15) and in referents. There was statistically significantly (P less than 0.0005) higher excretion of the nicotine metabolite, cotinine, in the urine of 49 children with asthma (geometric mean 10 ng/ml) compared with 77 referents (4.8 ng/ml). Maternal smoking was statistically significantly more prevalent among the asthmatics than among the referents (relative risk = RR = 2.6, 95% C1 = 1.2-5.3). In conclusion, the exposure to environmental tobacco smoke in asthmatic children was higher than among healthy children, indicating that passive smoking may be a predisposing and/or aggravating factor for childhood asthma. PMID- 1928657 TI - Allergen-antibody complexes can efficiently prevent seasonal rhinitis and asthma in grass pollen hypersensitive patients. Allergen-antibody complex immunotherapy. AB - We have prepared antigen-antibody complexes from grass pollen allergens and autologous specific antibodies isolated by immunoadsorption from the serum of allergic patients. These complexes were inoculated into patients in a double blind trial to evaluate their effect on grass pollen-related rhinitis and bronchial asthma. Thirty-eight grass pollen-hypersensitive patients were allocated to three groups; patients in the first two groups were treated with antigen-antibody complexes at different ratios and dosages and were compared with the third group who received the placebo carrier buffer alone. In addition, we treated a fourth group who had already received antigen-antibody complex inoculation during the previous pollen season. Injections were given every 2 weeks during the pollen season, starting 5 weeks prior to it. Tolerance was excellent with no signs of local or systemic side effects. The treatment prevented nasal symptoms while enabling the patients to reduce antihistamine intake. Bronchial asthma was virtually absent in the treated groups even though no bronchodilators or corticosteroids had to be taken. Specific IgE antibodies did not increase during the pollen season nor did IgG "blocking" antibodies. Inoculation of allergen-antibody complexes could provide a valuable alternative for the treatment of immediate hypersensitivity to airborne allergens as it appears to be safe and rapidly efficacious. This treatment offers several advantages compared to conventional hyposensitization and is characterized by the absence of an increase in specific IgG antibodies. PMID- 1928658 TI - Reproducibility of leukotriene D4 inhalation challenge in asthmatics. Effect of a novel leukotriene D4/E4-antagonist (SR 2640) on leukotriene D4-induced bronchoconstriction. AB - We have studied the reproducibility of a bronchial leukotriene (LT) provocation test in asthmatics, and the effect of prior treatment with an oral leukotriene D4/E4 antagonist (SR 2640) on LTD4-induced bronchoconstriction in nine asthmatics in a double-blind placebo-controlled randomized cross-over trial. The reproducibility of the bronchial leukotriene provocation test was high. For a specific patient, the replication variance is 0.2303, and the standard deviation is thus 0.4799, corresponding to 48%, i.e. one halving of the dose or half doubling of the dose. SR 2640 antagonised LTD4 induced bronchoconstriction causing a mean shift of 48% to the right of the dose-response curve as compared with placebo (95% confidence interval being 11-137%). This study demonstrates that bronchial LTD4 provocation test is a safe and reproducible method in asthmatics, and that the method can be used to detect LT-antagonism; furthermore that SR 2640 is a weak LTD4-antagonist in asthmatics. PMID- 1928660 TI - Is intrinsic asthma a hereditary disease? AB - Although studies of families, inbred populations and twins have established that asthma has a hereditary basis, little evidence has shown that intrinsic asthma has an increased familial occurrence. To document this issue, we compared the prevalence of asthma in families of intrinsic asthmatics, extrinsic asthmatics and non-asthmatics. The intrinsic asthma group included those with negative skin tests to common aero-allergens (n = 117). The extrinsic asthma group included those with one or more positive skin tests (n = 164). The non-asthmatic group (n = 224) was recruited at a check-up center. The siblings of each subject completed a standardized questionnaire on history of asthma. The results showed that asthma was more prevalent (P less than 0.001) in siblings of intrinsic asthmatics (8.9%) than in siblings of the non-asthmatic group (2.4%). The prevalence of asthma in siblings of intrinsic and extrinsic asthmatics was similar. In conclusion, both intrinsic and extrinsic asthma have an increased family occurrence. PMID- 1928659 TI - Pollen sensitization and allergy in children depend on the pollen load. AB - We investigated the influence of grass and birch pollen load on specific IgE response, skin prick test reactivity, and manifest allergic disorders of the eyes and respiratory tract. The study population was two groups of 200 children each, matched in sex and age, who were domiciled in areas with high and low pollen load, respectively. In the children from the area with high pollen load, the grass pollen load was 1.7 times higher than in the other and only specific IgE to grass pollen was found to be present more frequently (23.5% as against 12.5%; P less than 0.01). In the same area, the birch pollen load was 2.8 times higher, which caused specific IgE in 10.5% as against 3.5% of the other group (P less than 0.01) as well as positive skin prick test in 9.0% as against 3.5% (P less than 0.05). Reports of subjective complaints were rare among the group with high pollen load but the total number did not amount to a statistically significant increase. There was no difference between the two groups concerning sensitization and allergy to house dust mite. This suggests that the influence of the pollen load is strongest on the development of specific IgE, and less on skin test reactivity and manifest allergies. PMID- 1928661 TI - Aspergillus fumigatus specific IgE and IgG antibodies for diagnosis of Aspergillus-related lung diseases. AB - IgE and IgG antibodies against Aspergillus fumigatus were detected by crossed radio immunoelectrophoresis (CRIE) on the sera of seven patients with aspergilloma, six patients with allergic broncho-pulmonary aspergillosis (ABPA) and 25 patients with extrinsic asthma with Aspergillus allergy. IgE-CRIE analysis indicated the presence of A. fumigatus-specific IgE in sera of patients with ABPA and Aspergillus asthma but not of aspergilloma patients. IgG-CRIE showed that both aspergilloma and ABPA patient sera contained high levels of circulating specific IgG antibodies in contrast to sera of Aspergillus asthma patients, which did not show detectable amounts of Aspergillus-specific IgG antibodies. Specific IgE binding could be demonstrated for the major allergens Ag-10 and AG-40 in all ABPA patients, in 80% of Aspergillus asthma patients but not in sera from aspergilloma patients. Specific IgG antibodies directed towards the major allergens could be detected in most of the aspergilloma patients, between 30-70% of the ABPA patients but not in sera from patients with Aspergillus asthma. PMID- 1928662 TI - Liposomes as vehicle for allergen presentation in the immunotherapy of allergic diseases. AB - Liposomes are non-toxic, biodegradable and weakly immunogenic lipid vesicles which can be used as immunomodulating agents. In the present study, multilamellar vesicles (MLV) and small unilamellar vesicles (SUV) were used to incorporate an allergenic protein from Artemisia scoparia pollen. MLV incorporated more allergenic protein than SUV. To assess the immunomodulating effect of allergen entrapped in liposomes, Swiss strain mice (made IgE responders) were injected with either free allergen or liposome-entrapped allergen (LEA) and their immune response was measured in terms of specific IgG and specific IgE levels. Results indicated that specific IgE response was significantly lower in mice injected LEA (P less than 0.02) than in mice injected free allergenic protein. Although specific IgG response was higher in mice injected LEA, there was no statistically significant difference between the two groups. Potential use of liposomes as non immunogenic biocompatible vehicle for antigen presentation in immunotherapy will be discussed. PMID- 1928663 TI - Non-steroidal treatment of pollen-induced conjunctivitis: comparison of different pharmacological protocols. AB - Pharmacological treatment of allergic conjunctivitis may be based on the therapeutic use of topical steroids; however, because of the side effects, steroids are not clinically suitable in either prolonged treatment, or pollinosis. Because non-steroidal topical drugs are suitable in prolonged treatment, this single-blind study evaluated the following topical drugs: cromoglycate plus chlorphenamine, cromoglycate plus tetryzolin and imidazolin plus nafazolin, compared with placebo. The results confirm significant clinical efficacy of these drugs on signs and symptoms compared with placebo. Thus, "non steroidal" topical drugs should be the preferred choice in prolonged forms of pollen-induced (e.g. Parietaria and/or grasses) conjunctivitis. PMID- 1928664 TI - Inaccurate assessment of diamine oxidase activity in platelet-rich plasma. PMID- 1928665 TI - Getting there. PMID- 1928667 TI - Plasma etomidate levels in mother and fetus. AB - The most commonly used induction agent in anaesthesia for Caesarean section is still thiopentone. The increasing incidence of Caesarean section for delivery of premature babies from a hostile environment may call in question the assumption that the dose of thiopentone received by the neonate will not cause depression in the hours following birth. Previous studies on thiopentone for Caesarean section have shown inconsistency in umbilical vein/maternal vein ratios. We have studied plasma etomidate levels in maternal and umbilical blood at the time of delivery to see whether equilibrium occurs with this agent. We were able to demonstrate an umbilical/maternal vein etomidate ratio of 0.5 (SD 0.18), with no relation to time in the range encountered. Also, the uterine artery/uterine vein etomidate ratio was 0.86 (SD 0.33), suggesting that etomidate uptake into the fetus is effectively complete. Further, in all cases the neonatal plasma etomidate levels were less than half those measured at recovery of consciousness in adults in other studies, despite a larger induction dose than is usually used. PMID- 1928666 TI - The first 24 hours after surgery. A study of complications after 2153 consecutive operations. AB - The first 24 hours of the postoperative course of 2153 consecutive patients who had operations at the Nottingham Hospitals were studied in detail. Five per cent of patients had serious complications during this period; 15% of those having major operations, 1.8% having intermediate operations and 1.4% having minor operations. Thus, a significant number of patients were in an unstable condition for many hours after they were discharged from the main theatre recovery areas to the surgical wards. In 17 out of 23 patients who died and six out of six patients who suffered severe disability as a result of their surgery, the final outcome was a direct result of a sequence of events which began with an initial deterioration within 24 hours of surgery. We considered that, for at least 10 of these 29 patients, the outcome might have been different had more sophisticated postoperative facilities been available. In the light of this study we have identified the operations for which high dependency facilities are most likely to be required. PMID- 1928668 TI - Intra-arterial blood sampling for clotting studies. Effects of heparin contamination. AB - Prothrombin time and activated partial thromboplastin time were measured in two groups of 30 patients each. Blood sampled from an arterial line after various discard volumes and from a central venous line were compared with direct venipuncture control samples. The arterial line flushing solution contained 1 unit of heparin per ml in group 1 and 2 units per ml in group 2. Our results confirmed that clotting studies carried out on blood samples from an arterial line or central venous line correlate well with those obtained from a venipuncture sample. The only exception was activated partial thromboplastin time in group 2 patients when the discard volume from the arterial line is only 2.5 ml above the deadspace volume of the connecting line. At least 5 ml of discard volume must be withdrawn before sampling, to obtain reliable results. PMID- 1928669 TI - Observations on deliberate dural puncture with a Tuohy needle: depth measurements. AB - Observations were made during the use of a Tuohy needle to perform deliberate dural puncture for the insertion of lumbar drains to improve operating conditions for intracranial aneurysm surgery. The most striking finding was the distance from identification of the epidural space to penetration of the dura. We postulate that this was because of tenting of the dura by the blunt Tuohy needle. This was facilitated by the absence of a negative epidural space pressure because an open system was used, which allowed time for pressure equilibration. This minimised the reactive forces across the dura. Aspiration and rotation of the Tuohy needle revealed dural puncture in some cases. PMID- 1928670 TI - Observations on deliberate dural puncture with a Tuohy needle: pressure measurements. AB - Pressure recordings were made during passage of a Tuohy needle from the interspinous ligament to the subarachnoid space for lumbar drain insertion. Epidural space pressures were always positive. Negative pressures were seen only at the moment of entry into the subarachnoid space. These were artefactual and were caused by tenting of the dura by the blunt Tuohy needle. Use of a closed measurement system such as this facilitates the development of large transdural pressure gradients because of the inability of the epidural space pressure to equilibrate with atmospheric pressure. This may contribute to ease of dural puncture. PMID- 1928671 TI - A survey of secondary transfers of head injured patients in the south of England. AB - A survey by questionnaire was carried out to look into the provision of facilities for the secondary transfer of head injured patients, as well as difficulties encountered. An 84.6% response rate was achieved from 110 hospitals in six regions in the south of England. The results showed that 21% of hospitals had been unable to make a transfer in the previous year, and delays were commonly experienced by 23.7% of hospitals. The nursing attendance during transfer was satisfactory, but the quality of medical escort was poor, and the standard of monitoring equipment available was unacceptable. Methods of improving the situation include implementation of the recommendations of the Royal College of Surgeons, as well as the Association of Anaesthetists' recommendations for standards of monitoring and provision of intensive care. PMID- 1928672 TI - Continuous thoracic epidural fentanyl for post-thoracotomy pain relief: with or without bupivacaine? AB - Twenty-five ASA 1 or 2 patients undergoing thoracotomy were entered into a prospective, randomised, double-blind study comparing thoracic epidural fentanyl alone and thoracic epidural fentanyl combined with 0.2% bupivacaine. Pain relief, pulmonary function and cardiovascular stability were assessed. Pain relief was superior in the bupivacaine series (p less than 0.05) during the first day after operation and this was accompanied by better oxygenation (p less than 0.05); the difference did not persist into the second day. Forced expiratory variables were reduced in both series to 50-60% of the values before operation throughout the study (p less than 0.05) and differences did not occur between the groups. The incidence of side effects attributable to epidural fentanyl was high, but hypotension did not occur. Small doses of bupivacaine administered together with fentanyl into the thoracic epidural space improve analgesia without causing hypotension. PMID- 1928673 TI - The automatic implantable cardioverter-defibrillator. Implications for anaesthetists. AB - This paper describes the anaesthetic management of a patient who had an automatic implantable cardioverter-defibrillator. The working principles of the device, the indications for its insertion and the postoperative complications, are discussed. An increasing number of cardioverter-defibrillators are being implanted in the UK. At least two general anaesthetics are required for each patient; one for implantation of the device and a second for testing its efficiency in terminating ventricular tachycardia and ventricular fibrillation. In future, the number of patients presenting for noncardiac surgical procedures is likely to increase, therefore every anaesthetist should be aware of the problems involved in management. PMID- 1928674 TI - Removal of a laryngeal foreign body using high frequency jet ventilation. AB - Aspiration of a foreign body into the respiratory tract is a common and serious accident in childhood. Laryngotracheal foreign bodies, although less common than bronchial foreign bodies, are potentially more dangerous. Removal is commonly achieved using a rigid ventilating bronchoscope. We report a 16-month-old boy who had an open safety pin impacted in his larynx. This was removed through a tracheostomy, using high frequency jet ventilation to maintain gaseous exchange. We believe that this is the first case in which this method of removal has been reported. PMID- 1928675 TI - Extracorporeal circulation in the management of massive propranolol overdose. AB - A case of refractory hypotension following propranolol overdose is reported. Management included isoprenaline, glucagon and extracorporeal circulatory support using femoral vein-femoral artery bypass. The unreliability of neurological observations, especially unreactive pupils, in the presence of drug overdose is reiterated. PMID- 1928676 TI - Possible inadvertent subdural block following attempted stellate ganglion blockade. AB - A case is reported of suspected inadvertent subdural block following attempted stellate ganglion blockade for relief of cervicobrachial pain in a patient suffering from reflex sympathetic dystrophy. Possible complications due to neuraxial spread of local anaesthetics while performing a cervicothoracic ganglion blockade are considered. PMID- 1928677 TI - An assessment of the Cerebrotrac 2500 for continuous monitoring of cerebral function in the intensive care unit. AB - Experience of the use of the Cerebrotrac 2500 EEG monitor in 17 patients subjected to artificial ventilation in an intensive care unit is reported; seven were receiving continuous sedation with morphine, midazolam and propofol singly or in combination and 10 received both sedation and the neuromuscular blocking agent, atracurium. The processed EEG patterns could not be precisely correlated with a standard clinical scoring system but were useful in determining the adequacy of sedation, particularly when a muscle relaxant was used. The monitor also shows considerable promise in the management of the paralysed patient with widespread convulsive activity in whom ischaemic brain damage may be occurring from epileptiform activity in the absence of any clinical manifestation. The ability to detect cerebral irritability or isolated epileptiform discharges using this apparatus is, however, questionable. The equipment was easy to use and robust; the running costs were 9.5p per hour. PMID- 1928678 TI - The Extensometer. Potential applications in anaesthesia and intensive care. AB - The Extensometer is a new device capable of continuous accurate measurement of length over convex surfaces with a rapid response rate. This makes it a powerful research tool and a useful clinical instrument, particularly in the field of respiratory monitoring. This paper describes the principles behind the device. The linearity of its response was demonstrated in laboratory tests and its ability to quantify abdominal and chest wall movement was assessed in anaesthetised patients. Potential applications in the field of ventilatory pattern analysis and respiratory monitoring in anaesthesia and intensive care are discussed. PMID- 1928679 TI - The Alton Dean pressure infusor: an evaluation. AB - An automatically pressurised infusor system, the Alton Dean infusor, has been compared with two types (cloth and plastic) of commonly used pneumatically pressurised bags. All the infusors had reasonably accurate pressure gauges but pressure could only be consistently maintained with the cloth infusors or with the Alton Dean infusors when connected to a compressed air supply. Sequential fast infusions were possible with all infusors, but simultaneous infusions could be limited in number when the pressure infusor was connected directly to pipeline gas. One of the Alton Dean pressure infusors tested had a leak in the pressurisation system, and the pressure adjustment valves were difficult to manipulate. These may require modification. PMID- 1928680 TI - The use of the Penlon Nuffield 200 in a monoplace hyperbaric oxygen chamber. An evaluation of its use and a clinical report in two patients requiring ventilation for carbon monoxide poisoning. AB - We modified a Penlon Nuffield 200 for use in a monoplace hyperbaric oxygen chamber by feeding back the chamber pressure to the reducing valve of the Nuffield 200. This provides a compensating mechanism, allowing the ventilator to deliver adequate tidal volumes at pressures of up to 3 atmospheres. We report the laboratory testing of the ventilator and our experience of ventilating two patients with carbon monoxide poisoning. Although compensation is not complete the modification is adequate for short-term clinical use in patients in whom the airway is compromised but who need hyperbaric oxygen therapy. PMID- 1928681 TI - Comparison of propofol and thiopentone for laryngeal mask insertion. AB - Conditions for insertion of the laryngeal mask were assessed following induction of anaesthesia with either propofol 2.5 mg/kg or thiopentone 4.0 mg/kg in 80 patients premedicated with diazepam 10 mg. Insertion following induction with thiopentone resulted in a greater incidence of gagging (p less than 0.01). The use of additional induction agent, where necessary, resulted in no ultimate significant difference between the groups for the provision of satisfactory conditions. PMID- 1928682 TI - Nurse-controlled intravenous analgesia. Effective control of pain after thoracotomy. AB - Nurse-controlled continuous intravenous opioid analgesia was evaluated prospectively in 60 patients after thoracotomy. The rate of opioid infusion was adjusted, and bolus does were administered, as required to maintain patient comfort. The patients evaluated their pain using a visual analogue scale on 10 occasions during the first 48 hours after surgery. Pain scores remained consistently low throughout the period of measurement. Over the study period there was a 30-fold difference between the least and greatest requirement for opioid to achieve adequate analgesia. No major side effects were encountered. The study indicates that nurse-controlled intravenous analgesia can be successfully used for pain relief after thoracotomy. PMID- 1928684 TI - The role of the teaching hospital. A survey of paediatric anaesthetic techniques used by trainee anaesthetists on a regional training scheme. AB - All trainee anaesthetists on the Northern Ireland training scheme were surveyed about the techniques they use when anaesthetising elective paediatric cases. We compared the practice of doctors with specialist paediatric training to that of others and discovered that trainees with specialist training were more likely (p less than 0.05) to admit parents during induction, but were less likely (p less than 0.05) to visit their patients pre-operatively and routinely to use suxamethonium. Other general findings were confusion over the re-use of halothane and extensive involvement of trainee anaesthetists in neonatal resuscitation. PMID- 1928683 TI - Propofol: bolus or continuous infusion. A day case technique for the vaginal termination of pregnancy. AB - Forty patients undergoing vaginal termination of pregnancy were randomly allocated to receive a propofol anaesthetic using either a repeat bolus or infusion technique. The Ohmeda 9000 Infusion Pump was used in the study. Patients in the infusion group recorded significantly longer induction times, greater maintenance doses and prolonged immediate recovery characteristics. Both techniques offered cardiovascular stability but no advantages were demonstrated for the infusion technique over a conventional repeat bolus method. PMID- 1928685 TI - Comparison of two techniques for sedation in dental surgery. AB - Forty-eight patients were randomised to receive sedation of outpatient dental surgery with midazolam. Sedation was given using the Verrill technique (24 patients) and the Glasgow Dental Hospital technique (24 patients). The differences in recovery and patient acceptability were assessed. There was no statistical difference in mean recovery times between the two groups. Memory function was examined using the Warrington memory test. Fewer patients in the Verrill group recalled the injection of local anaesthetic but they demonstrated memory defects 4 hours after sedation for words and 3 hours for faces. The Glasgow Dental Hospital group demonstrated memory defects for words up to 2 hours following sedation, but not for faces at any time. Thirty-eight patients would have dental surgery again with similar sedation. The dental surgeon found conditions for surgery inadequate in two patients. In view of the shorter duration of amnesia we recommend the Glasgow Dental Hospital technique. PMID- 1928687 TI - Variables of patient-controlled analgesia. PMID- 1928686 TI - Haemodynamic effects of propofol in children. AB - The haemodynamic effects of induction of anaesthesia with propofol in children were studied. Two hundred and sixteen children (ASA 1) were randomly allocated to receive one of six different doses of propofol, from 1.6 mg/kg to 2.6 mg/kg, in 0.2 mg/kg increments. Noninvasive measurement of blood pressure showed that mean arterial pressure was reduced by approximately 15% after 1 minute, and by 30% after 5 minutes. The reduction in pulse rate over a 5-minute period was approximately 17%. These changes were similar in each group, regardless of the dose administered. The propofol was mixed with lignocaine, 0.5 mg/ml, and the incidence of pain on injection into a vein on the dorsum of the hand was 24%. We conclude that, within the dose range of our study, the haemodynamic disturbance after induction of anaesthesia with propofol in children is not dose related. PMID- 1928688 TI - Two incidents of complete failure of OAV 7750 ventilators. PMID- 1928689 TI - Ohmeda 9000 syringe pump. PMID- 1928690 TI - Does an acute pain service require a high dependency unit? PMID- 1928691 TI - Regional anaesthesia and cough effectiveness. PMID- 1928692 TI - Polarisation of a 2.5 mm tracheal tube. PMID- 1928693 TI - The length of RAE preformed tubes. PMID- 1928694 TI - Another antipollution device for the Jackson-Rees modification of Ayre's T-piece system. PMID- 1928695 TI - 'Spinal' headache--with no headache. PMID- 1928696 TI - Ventricular fibrillation during examination of nose. PMID- 1928697 TI - Duplicate markings on an epidural catheter. PMID- 1928698 TI - Raised intra-abdominal pressure and renal failure. PMID- 1928699 TI - Acute choreoathetoid reaction to propofol. PMID- 1928700 TI - Propofol and excitatory sequelae in dogs. PMID- 1928701 TI - Hazard with the Penlon AM 700 anaesthetic machine. PMID- 1928702 TI - Riddle of the persistent leak. PMID- 1928703 TI - Intermittent obstruction of tracheal tube revealed during pressure-supported ventilation. PMID- 1928705 TI - Inadvertent submucosal penetration with a minitracheostomy cannula inserted by the Seldinger technique. PMID- 1928704 TI - Long distance transport of the critically ill. PMID- 1928706 TI - A technique to avoid dural puncture by the epidural catheter. PMID- 1928707 TI - Skiers neck: an unusual cause of difficult intubation. PMID- 1928708 TI - [Protamine toxicity and mediators. Is the use of antagonists helpful?]. PMID- 1928710 TI - [Hemodynamic effects of a combination of general and peridural anesthesia during anesthesia induction in geriatric patients]. AB - For major operative procedures in the lower abdomen and many orthopedic procedures such as total hip replacement, a combination of general and epidural anesthesia is used. In order to investigate the hemodynamic effects of such a combination in 14 geriatric patients aged 63-80 years who were undergoing total hip replacement, cardiovascular monitoring was established by an arterial line and a pulmonary artery catheter. The epidural anesthesia was achieved with bupivacaine 0.5% in a dose calculated to obtain a block up to Th 6. General anesthesia was then induced and maintained with midazolam, fentanyl, pancuronium bromide, and a 2:1 nitrous oxide-oxygen mixture. Hemodynamic measurements were established before and 30 min after induction of the epidural anesthesia and 20 min after the induction of general anesthesia. After bupivacaine was injected the loss of sympathetic tone produced a systolic arterial blood pressure decrease from 174 +/- 22 to 136 +/- 28 mmHg (p less than 0.05) and a decrease in heart rate from 73 +/- 12 to 66 +/- 10 min-1 (p less than 0.05). The cardiac index did not change, but the peripheral vascular resistance decreased significantly. Because intravenous fluids were given simultaneously, preload could be maintained. Oxygen delivery and oxygen extraction did not change. During general anesthesia a significant drop in cardiac output was observed from 3.0 +/- 0.6 l/min.m2 to 2.3 +/- 0.4 l/min.m2 (p less than 0.05). The systolic arterial blood pressure decreased to as low as 95 +/- 17 mmHg (p less than 0.05) and oxygen delivery decreased from 500 +/- 125 ml/min.m2 to 323 +/- 84 ml/min.m2 (p less than 0.05). PMID- 1928709 TI - [Complications caused by protamine. 1: Pharmacology and pathophysiology]. AB - Protamine is a strongly alkaline polypeptide with a molecular weight of about 4500. Protamine solutions contain paraben compounds as antimicrobial agents. Rapid neutralization of heparin by protamine may cause an anaphylactoid reaction characterized by a non-immunogenic histamine release and by unknown mediators mechanisms. This response is associated with systemic peripheral vasodilation resulting in slight to moderate hypotension. Weak negative inotropic effects by mechanisms different from the reduction of ionized calcium concentrations may also contribute to systemic hypotension. Apart from these mostly slight reactions, severe reactions may occur with life-threatening systemic hypotension, bronchospasm and, in rare cases, death. They are caused by anaphylactic/anaphylactoid reactions resulting in catastrophic pulmonary vasoconstriction which induces right and eventually global ventricular failure. Sensitization to protamine (anaphylactic) and anaphylactoid reactions are the underlying mechanisms. The majority of anaphylactic/anaphylactoid reactions are associated with complement activation and the release of anaphylatoxins C3a and C5a. These activate the cyclo-oxygenase pathway of the arachidonic acid metabolism in yet unidentified cells, probably within the lung. As a result, thromboxane and prostaglandins are released. Thromboxane is the pivotal mediator responsible for the pulmonary vasoconstriction and, presumably, also for the bronchospasm during protamine reactions. The pronounced activation of polymorphonuclear leukocytes and the decrease in platelet counts may reflect a mere epiphenomenon. The degree of right ventricular afterload increase at which systemic hypotension requiring immediate therapy would occur depends mainly on the contractile state of the heart. Potential risk patients for severe protamine reactions are depot insulin-dependent diabetics and patients with prior exposure to protamine. PMID- 1928711 TI - [Automated, continuous ST segment analysis in the ECG as a monitor of myocardial ischemia during aortocoronary bypass surgery]. AB - Patients with coronary artery disease (CAD) who are subjected to cardiac and major noncardiac surgical procedures have a high incidence of perioperative myocardial ischemia. Earlier studies in patients undergoing coronary artery bypass graft surgery (CABG) indicated the frequency of postoperative myocardial infarction to be directly proportional to the incidence and severity of pre bypass myocardial ischemia. METHODS: We investigated the incidence of pre-bypass ischemia in 50 patients undergoing elective CABG using an automated ST segment monitoring system (Marquette 7010). Analyzing leads I, II, and V5, this device measures ST segment deviations 60 ms after the J-point. Occurrence of myocardial ischemia was defined as follows: new ST segment deviations larger than 1 mm = 0.1 mV that lasted for more than at least 10 consecutive heartbeats. RESULTS: In 19 out of 50 patients (38%) we found 96 episodes of myocardial ischemia in the pre bypass period; 47% of all ischemic episodes were associated with significant hemodynamic changes, e.g., tachycardia, hypertension, or hypotension. The incidence of ischemia was different between population sub-groups: patients with a previous infarction had a lower incidence of ischemia (35%) than patients without infarction (44%). Patients with preoperative left ventricular end diastolic pressure (LVEDP) less than 15 mm Hg had a lower incidence of ischemia (29%) than patients with LVEDP greater than 15 mm Hg (50%). Patients treated preoperatively with beta-blockers showed a significantly lower incidence of ischemia (9%) when compared to untreated patients (46%, p less than 0.05). No difference was found between patients with or without unstable angina pectoris or between patients of NYHA classes II, III, or IV. Postoperative myocardial infarction occurred in 2 patients, both with evidence of pre-bypass myocardial ischemia. CONCLUSION: Our study confirms that automated ST segment analysis is able to detect myocardial ischemia similarly to that documented in previous studies using conventional ECG lead analysis. PMID- 1928712 TI - [Recombinant erythropoietin in autologous blood donation]. AB - As a result of the AIDS crisis, public and physician pressure have increased the utilization of autologous blood products. Attitudes about homologous blood transfusion, however, have changed dramatically in recent years. A large segment of the population undergoing elective surgery is elderly and therefore has a significant incidence of cardiovascular disease and a slow response of the erythropoietic system when acute anemia occurs. However, preoperative autologous blood donation programs require 2-5 weeks to complete; the average yield is only 2.2 units per patient. As a consequence, autologous predonation is underused and homologous transfusion cannot be completely avoided in all patients. For several years recombinant human erythropoietin (rHuEPO) has been available and has been successfully used in the treatment of patients with renal anemia. This study evaluated the effect of r-HuEPO on patients with preoperative autologous blood collection. METHODS. Ten patients of both sexes scheduled for hip arthroplasty underwent a preoperative autologous program. During a period of 23 days prior to surgery autologous blood donation was performed with 7.5 ml/kg withdrawal on four occasions, the last one 5 days prior to surgery. Five patients were randomly treated with subcutaneous injections of rHuEPO (Erypo, Cilag GmbH, Sulzbach; Distributor: Fresenius AG, Oberursel, FRG) 200 IU/kg seven times, starting 3 days after the first blood withdrawal. All patients (n = 10) received oral iron therapy with iron sulphate 304 mg/die (= 100 mg iron/die). Patients with hypertension or recent myocardial infarction were excluded from the study. The hemoglobin level before donation had to be at least 11.0 g/dl. On each study day, a complete blood count and platelets, differential, and reticulocyte count were determined by standard methods as were transferrin, ferritin, and total iron binding capacity. Blood loss and blood consumption during and after the operation were registered. The indication for blood transfusion (autologous/homologous) was based on hemoglobin values, which were not acceptable below 8.5 g/dl. RESULTS. No side effects of rHuEPO treatment were observed. Blood loss ranged from 650 to 1100 ml intraoperatively and 400 to 950 ml postoperatively with no differences between the groups. Patients with rHuEPO had no autologous red cell concentrates (aRCC) during the operation; two of them had two units of aRCC on the 2nd postoperative day. Two of the patients in the control group had intraoperative blood transfusions (2 and 3 units aRCC, respectively); all patients in this group were transfused postoperatively: 12 of the 20 units collected were utilized. At the onset of the operation the mean hemoglobin value in patients with rHuEPO was 13.5 +/- 0.4 g/dl compared to 11.3 +/- 0.3 g/dl in the controls. Reticulocytes increased significantly during the investigation period. On the 2nd, 3rd, and 4th days of autologous blood collection and before the onset of surgery, the number of reticulocytes was significantly greater in rHuEPO patients than in the controls. Further laboratory variables such as transferrin, ferritin, and total iron-binding capacity did not change significantly during the investigation period; there were no significant differences between the two groups. DISCUSSION. The results of the present study show that rHuEPO leads to an increase in reticulocytes with maintenance of hemoglobin levels during the phlebotomy program. As a consequence, patients with anemia and particular contraindications to homologous blood derivatives (irregular antibodies, Jehovah's Witnesses) may be able to undergo major surgery successfully. The possibility of shortening the intervals between phlebotomies would seem to be of major advantage; our data also suggest that an aggressive autologous blood collection program would increase yields over present programs. In our institute a minimum hemoglobin level of 11.5 g/dl is accepted for autologous donation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1928713 TI - [The effect of clonidine on the intrapulmonary right-to-left shunt in one-lung ventilation in the dog]. AB - Many vasoactive drugs--vasoconstrictors as well as vasodilators--impair the efficiency of hypoxic pulmonary vasoconstriction (HPV) and may cause dangerous hypoxemia during one-lung ventilation (1-LV). The effect of clonidine, a widely used alpha 2-agonistic antihypertensive agent, on intrapulmonary right-to-left shunt (Qs/Qt) during 1-LV has not yet been studied. METHODS. Twenty anesthetized beagle dogs were instrumented with a 7F Swan-Ganz catheter and an arterial line. A left thoracotomy in the lateral position was performed and the left main bronchus was prepared for clamping. Intravenous clonidine (5 micrograms/kg) was administered to 10 dogs. Anesthesia was maintained with either thiopental and fentanyl or halothane (0.8 insp. vol%) and fentanyl. The ventilatory frequency (100% O2, tidal volume 150 ml/kg) was adjusted to obtain an end-expiratory CO2 of 4.5%. Each dog underwent the following experimental sequence: (1) baseline measurements with 2-LV; (2) 20 min 1-LV (left lung atelectasis was achieved by clamping the left main bronchus); and (3) 20 min 2-LV. After allowing 30 min for conversion from i.v. to halothane anesthesia or vice versa, the procedure was repeated (5 dogs in each group received first i.v. and 5 dogs first halothane anesthesia). RESULTS. Qs/Qt was slightly but not significantly higher under halothane anesthesia in both groups during 1-LV as well as 2-LV (Table 1). No differences existed between the halothane and i.v. groups with regard to arterial pO2 and cardiac index. In the control group (i.v. or halothane, n = 20) Qs/Qt increased during 1-LV from 10.8 +/- 2.8% (mean +/- S.D.) to 26.6 +/- 5.5%, and in the clonidine group (i.v. or halothane, n = 20) from 7.2 +/- 2.3% to 18.3 +/- 5.4%. These differences between the control and clonidine groups are significant (P less than 0.001) for 1-LV as well as 2-LV. Arterial pO2 during 1-LV was reduced less in the clonidine group (573 +/- 48 to 390 +/- 99 mmHg) than in the control group (550 +/- 44 to 323 +/- 94 mmHg) (P less than 0.05). During 1-LV no significant differences between the two groups could be detected with regard to pulmonary artery pressure, mixed-venous pO2, pCO2, and pH. Heart rate, cardiac index, and oxygen uptake were significantly lower and arteriovenous O2 difference was significantly greater in the clonidine group, indicating better control of sympathoadrenergic activity under clonidine. CONCLUSIONS. We conclude that pretreatment with clonidine improves HPV during 1-LV. This effect of clonidine is probably due to reduced sympathetic nervous system activity. PMID- 1928714 TI - [Selective cerebral hypothermia following cardiac arrest in the cat]. AB - The aim of the present study was to introduce a new method of external selective brain cooling in cats. By means of this device, which mainly consisted of a head sized, closely fitting copper basin, it was possible to reduce brain temperature rapidly. The resultant difference between core and cerebral temperatures amounted to mean values of about 10 degrees C after a 20-min cooling period. Ventricular fibrillation lasting for 15 min was induced in 23 healthy adult cats by internal cardiac electrical overpacing and followed by cardiopulmonary resuscitation (CPR). In several animals (n = 8) CPR efforts failed completely or they died without any indication of sufficient spontaneous circulation. In the initial postischemic period the remaining animals stayed normothermic and served as controls (n = 7) or received external brain cooling (n = 8), which was started simultaneously with CPR and continued for 30 min. During a survival time of 4 h cardiocirculatory function was stabilized pharmacologically and artificial respiration was performed, followed by transcardiac perfusion fixation. After removal from the skull, the brains were processed for histopathological evaluation of ischemic neuronal damage by light microscopy and morphometry. The clinical data obtained indicate that the described method provides a means for efficient heat exchange from within the intracranial space. Rapid, selective brain cooling could be achieved without any critical reduction of the core temperature and therefore, cardiac arrhythmias, a usual consequence of generalized hypothermia, could be avoided. The histopathological evaluation of ischemic neuronal damage showed a significantly higher percentage of unaffected cells in some areas of the cerebral cortex in animals treated with postischemic cerebral hypothermia than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928715 TI - [A life-threatening situation due to the central anticholinergic syndrome in a case of severe coronary disease]. AB - This report presents a case of central anticholinergic syndrome after general anesthesia in a patient with severe coronary heart disease. Eight years ago he had had two myocardial infarctions; after undergoing a bypass operation he suffered a third one. His angina pectoris had increased over the previous 6 months. General anesthesia was required for an ear operation; it was carried out as "balanced anesthesia" without any difficulties. After extubation, however, the patient became extremely agitated. Increasing myocardial work and oxygen consumption caused a life-threatening situation. The diagnosis was made immediately and the situation could be controlled by administration of physostigmine. PMID- 1928716 TI - [Disseminated tumor cell embolism of the lung as a cause of sudden death during general anesthesia]. AB - A 56-year-old woman was hospitalized because of jaundice, vomiting, and weight loss. Diagnostic measures were almost all negative except for computer tomography of the abdomen, which revealed a cyst in the pancreas. During performance of a diagnostic laparotomy the patient suddenly died, presenting with cyanosis and untreatable circulatory failure with a markedly elevated central venous pressure. Autopsy revealed pulmonary tumor-cell embolization. This rare cause of sudden death is characterized by the discrepancy between the clinical picture and the virtually negative preoperative diagnostic results. We present this case report as a reminder of this clinical entity and recommend an autopsy in every case of unexpected death under anesthesia. PMID- 1928718 TI - [Causes of death in intensive care surgical patients. A prospective study]. AB - Infection and sepsis are generally considered as causally related to death in intensive care unit (ICU) patients, but in several studies a decrease in infection rates was not associated with lower mortality. We therefore investigated the causes of death in surgical ICU patients, with special regard to the relationship between infection and mortality. MATERIAL AND METHODS. During the investigation period of 6 months, 502 patients were treated in the ICU (cardiac surgery: 222, thoracoabdominal surgery: 125, vascular surgery: 84, others: 14). In all patients each antibiotic therapy and infection was documented, as was the sepsis score. Definitions of infection and bacteriological monitoring were described in detail previously. In all deaths, attention was paid to an infection that was causally related to or contributed to death. In unclear cases a postmortem examination was performed. RESULTS. Forty-two patients died (8.4%). During the first 4 days 23 patients died, 11 within 24 h, because of severe trauma with severe underlying disease (main reason for death: cardiac 30%, cerebral 32%). Infections were not significant in these patients. Nineteen patients suffered from 1 or more infections (total 30). They died after a median of 16 days. The leading cause of death was multiple organ failure. In 7 of these patients a life-threatening infection was the reason for admission and, later, death. In 8 patients a nosocomial infection was causally related to or contributed to death. In the 4 other patients a postmortem examination excluded an infection as being responsible for death. DISCUSSION. More than one-half of the deaths were caused by severe trauma or severe underlying disease. Nosocomial infections could only be related to death in 1.6% of the 502 treated ICU patients. The influence of new therapeutic regimens on infection and mortality can therefore only be investigated in multicenter trials. PMID- 1928717 TI - [The seated position in patent foramen ovale?]. AB - Anesthetic management of patients presenting for posterior cranial fossa surgery in the seated position includes detection and treatment of venous air embolism. Atrial positioning of a central venous (cv) line may be verified by either X-ray or an atrial ECG tracing. We report a case where a chest X-ray film proved superior. A 26-year-old white female was scheduled for posterior cranial fossa exploration. A cv line was inserted via the left antecubital vein; the chest X ray film documented correct positioning of the catheter tip within the atrium but an aberrant course of the superior vena cava. Echocardiography was performed in the induction room and indicated a patent foramen ovale. In view of the risk of paradoxical air embolism, surgery was postponed. Subsequent cardiologic and radiologic examinations revealed a patent foramen ovale and a persisting left superior vena cava draining into a dilated coronary sinus. Surgery was rescheduled and carried out uneventfully in the prone position. This case demonstrates: 1) an advantage of a thoracic-X-ray film compared to atrial ECG tracing as not only the catheter tip position, but also the course of the catheter can be identified; and 2) the usefulness of preoperative screening for a patent foramen ovale in patients scheduled for surgery in the seated position. PMID- 1928719 TI - Influence of column temperature on the electrophoretic behavior of myoglobin and alpha-lactalbumin in high-performance capillary electrophoresis. AB - The influence of column temperature on the electrophoretic behavior of myoglobin and alpha-lactalbumin in high-performance capillary electrophoresis (HPCE) is presented. The major effect of temperature is to shorten the analysis time by decreasing the viscosity, but specific temperature effects on the protein migration behavior were also observed. Myoglobin, under high field (350 V/cm), was essentially temperature stable from 20 to 45 degrees C, but at constant current, a second form of myoglobin could be detected at both 214 and 410 nm. The initial form appeared to correspond to the Fe3+ and the second to the Fe2+ oxidation state of the heme iron. The rate of conversion from Fe3+ to the reduced Fe2+ in myoglobin, under given electrophoretic conditions, followed first-order kinetics with a rate constant at 30 degrees C of 304 s-1. A second protein, alpha lactalbumin type III, demonstrated a conformational transition that resulted in asymmetric peaks and sigmodial mobility plots versus temperature in the transition region. PMID- 1928720 TI - Particle size distribution by sedimentation/steric field-flow fractionation: development of a calibration procedure based on density compensation. AB - Because of the important but mathematically complex role played by hydrodynamic lift forces in sedimentation/steric FFF, applied generally to particles greater than 1 micron in diameter, retention cannot readily be related to particle diameter on the basis of simple theory. Consequently, empirical calibration is needed. Unfortunately, retention is based on particle density as well as size so that a purely size-based calibration (e.g., with polystyrene latex standards) is not generally valid. By examining the balance between driving and lift forces, it is concluded that equal retention will be observed for equal size particles subject to equal driving forces irrespective of particle density. Therefore by adjusting the rotation rate to exactly compensate for density, retention can be brought in line with that of standards, a conclusion verified by microscopy. Linear calibration plots of log (retention time) versus log (diameter) can then be used. This approach is applied to two glass bead samples (5-30 and 5-50 microns) using both a conventional and a pinched inlet channel. The resulting size distribution curves are self consistent and in good agreement with results obtained independently. PMID- 1928721 TI - Characterization of the chemical architecture of carbon-fiber microelectrodes. 1. Carboxylates. AB - A new method to characterize the chemical architecture of a carbon-fiber microelectrode surface is described. Derivatization of carboxyl groups on the carbon surface with a poly(oxyalkalene)diamine (Jeffamine ED-600), followed by biotinylation of the free amine, allowed the attachment of a fluorescein isothiocyanate (FITC) conjugate of ExtrAvidin. The fluorescence observed after excitation at 488 nm was imaged with a fluorescence microscope equipped with a CCD camera, yielding a spatial map of the distribution of modified carboxyl groups on the surface of the carbon fiber with 0.5-micron resolution. Colloidal gold particles (15 nm diameter) coated with ExtrAvidin were used in place of the FITC-ExtrAvidin, and the carbon-fiber surface was imaged with scanning electron microscopy on a submicron scale. This selective information regarding surface bound functional groups (i.e. carboxylates) has proven invaluable toward the rational design of novel sensors based on surface-modified ultramicroelectrodes. PMID- 1928722 TI - Nanoscale packed-capillary liquid chromatography coupled with mass spectrometry using a coaxial continuous-flow fast atom bombardment interface. AB - Nanoscale packed-capillary liquid chromatography (LC) columns have been coupled with mass spectrometry (MS) using a coaxial continuous-flow fast atom bombardment interface. The combined system has been applied to the analysis of mixtures of peptides, including synthetic mixtures of bioactive peptides and tryptic digests of proteins. Nanoscale packed-capillary columns offer two principal advantages for LC/MS analysis--high chromatographic separation efficiencies and low mobile phase flow rates. The high separation efficiencies facilitate the separation of complex mixtures, and the low mobile-phase flow rates reduce problems with coupling the LC effluent with the high-vacuum, high-voltage environment of sector MS ion sources. The columns used in this work were 50- or 75-micron i.d., 1-2 m long, packed with 10-micron C18 particles, using mobile-phase flow rates of 50 350 nL/min. PMID- 1928723 TI - Electrospray mass spectrometry: application of ion evaporation theory to amino acids. AB - We describe the result of applying the ion evaporation theory to a series of amino acids. The very good correlation (r = 0.98) of the natural logarithms of protonated molecule intensities observed by electrospray with the difference between the hydration free energies of molecules and the gas-phase binding free energies of molecules and protons in amino acids is consistent with the ion evaporation model. It seems that the difference in the protonated molecule intensities of amino acids obtained by electrospray can be explained by a scheme in which protonated molecules in the liquid phase are extracted into the gas phase after a charged droplet is formed. PMID- 1928724 TI - Evaluation of inductively coupled plasma mass spectrometry as an elemental detector for supercritical fluid chromatography. AB - Supercritical fluid chromatography coupled with inductively coupled plasma mass spectrometry shows high potential for the determination at ultratrace levels of organometallic compounds of environmental interest. In this study the determination of organotin compounds at ultratrace levels is demonstrated. In this work a supercritical fluid chromatography/inductively coupled plasma mass spectrometry (SFC/ICPMS) interface was developed. Separation of tetraalkyltin compounds shows detection levels in the subpicogram range (0.034 pg for tetrabutyltin; 0.047 pg for tetraphenyltin). The linear ranges are over 3 orders magnitude (1-1000 pg). The reproducibility of sample injections are better than 5% RSD. PMID- 1928725 TI - Process for groundwater cleanup. PMID- 1928726 TI - Analysis, imaging, and modification of microscopic specimens with accelerator beams. PMID- 1928727 TI - Robots in health care. PMID- 1928728 TI - Cadmium: toxicology and analysis. A review. PMID- 1928729 TI - Automated enzyme packed-bed system for the determination of vitamin C in foodstuffs. AB - A microprocessor controlled flow injection system is described for the determination of vitamin C in foodstuffs. The system is based on amperometric detection at a wall-jet electrode coupled with an ascorbate oxidase packed bed. A commercially available Cartesian robotic auto-sampler-dilutor is used as a means of fully automating the sample handling and dilution. Dithiothreitol (DTT) is used to reduce dehydroascorbic acid to ascorbic acid and to stabilize ascorbic acid standard solutions. Initially, the system was connected in series with a high-performance liquid chromatography column and ultraviolet (UV) detector to allow identification of possible interferents and to allow comparative evaluation of results. The system showed a linear response to the concentration of L ascorbic acid in the range 1-200 micrograms ml(-1) and was capable of detecting total vitamin C in a range of foodstuffs at a sample throughput of 15 samples h( 1). Correlations to existing methods of 0.98 were obtained. PMID- 1928730 TI - Spectrophotometric determination of ascorbic acid in pharmaceuticals by background correction and flow injection. AB - Background correction has been shown to be an effective and indispensable modification in the spectrophotometric determination of ascorbic acid. The decomposition of ascorbic acid in pharmaceutical samples was carried out by incubation with sodium hydroxide to give products that were insensitive to ultraviolet light. The rapid oxidation in air of ascorbic acid, especially in dilute solutions, was avoided by the use of the flow injection principle for spectrophotometric determination and by employing a carrier stream of an anti oxidizing nature consisting of 6 micrograms ml(-1) of 2-mercaptoethanol in 0.25% sulphuric acid. The optimized method with a single channel manifold made use of a carrier stream flow rate of 1.1 ml min(-1), an injection volume of 50 microl, a delay coil of 50 cm (0.5 mm i.d.) and detection at 245 nm. The throughput was at least 180 injections h(-1). The proposed flow injection method yielded results for the analysis of 0-20 micrograms ml(-1) of ascorbic acid that were 99-102% (relative standard deviation 0.6% or better) in agreement with those produced by comparable methods involving titration with iodine, chloranil or 2,6 dichlorophenolindophenol [4-(2,6-dichloro-4-hydroxyphenylimino)cyclohexa-2,5 dieno ne], and high-performance liquid chromatography. When the agreement was not good (as low as 14% with respect to the method being compared), this was traced to the presence of substances which are known to interfere in one or other of the methods of comparison. PMID- 1928731 TI - Spectrophotometric flow injection determination of trace amounts of thiocyanate based on its reaction with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol and dichromate: assay of the thiocyanate level in saliva from smokers and non smokers. AB - A simple and very sensitive spectrophotometric flow injection (FI) procedure for the determination of trace amounts of thiocyanate is described. The proposed method is based on the reaction between thiocyanate and 2-(5-bromo-2-pyridylazo) 5-diethylaminophenol, which, in 2 mol dm-3 acidic media in the presence of a strong oxidizing agent, produces an intensely coloured product. Several oxidants are potentially applicable, but it is shown that dichromate is preferable. As the reaction product formed is unstable and the signal inherently is recorded on a high background level, it is demonstrated that FI constitutes an ideal method in order to monitor reproducibly and repeatedly the kinetically transient signal that is obtained. Based on optimization by a factorial experimental design, the detection limit of the procedure was found to be 3.5 mumol dm-3, and the standard deviation between samples was 0.16 mumol dm-3. No significant interferences were observed; a 1000-fold excess of cyanide could readily be tolerated within the experimental error. With a sample volume of 50 microliters being injected, the sampling frequency was 60 samples h-1. The system was tested with saliva samples from non-smokers and smokers, and the results show that it is possible to distinguish between these two categories of individuals. As an added benefit, the detection limit of the analytical procedure allows the samples to be diluted 100 fold, so that centrifugation for 5 min is the only preliminary sample preparation that is necessary. PMID- 1928732 TI - Kinetic determination of iodide in pharmaceutical and food samples. AB - A kinetic method for the determination of iodide based on its inhibitory effect on the Pd(III) catalysed reaction between ethylenediaminetetraacetic acid (EDTA) Co(III) and the hypophosphite ion is described. The reaction was followed spectrophotometrically by measuring the decrease in the absorbance at 540 nm. Under the optimum experimental conditions of 2.6 x 10(-3) mol dm(-3)Co(III)-EDTA, 0.4 mol dm(-3)H2PO2-, pH 3.2 (adjusted with Britton-Robinson buffer), 0.57 micrograms ml(-1) Pd(III) and 20 +/- 0.2 degrees C, iodide was determined in the range 2-28 ng ml(-1). The method was applied to the determination of iodide in pharmaceutical products, iodinated salts, cow's milk and infants' powdered milk. PMID- 1928733 TI - Occurrence, handling and chromatographic determination of pesticides in the aquatic environment. A review. PMID- 1928734 TI - Comparison of the measurement of serum cotinine levels by gas chromatography and radioimmunoassay. AB - Standard cotinine solutions, controls and human serum samples containing cotinine have been measured by both radioimmunoassay (RIA) and gas chromatographic (GC) techniques. Cross-checks on standards and controls showed good agreement. However, for samples containing greater than 50 ng ml-1 of cotinine, RIA gave results on average 60% higher than GC. Determinations by using RIA and GC on samples containing less than 7 ng ml-1 of cotinine gave no significant correlation. The importance of the age of the serum sample has been investigated, and it is suggested that the age may affect the determination when dealing with low levels of cotinine. PMID- 1928735 TI - Adsorptive preconcentration for voltammetric measurements of trace levels of chlorprothixene. AB - The psychotherapeutic drug chlorprothixene is shown to adsorb strongly onto a glassy carbon surface in an open circuit. By using this phenomenon to preconcentrate the drug at a glassy carbon electrode prior to differential-pulse voltammetric measurements, sensitivity at the ppb level is readily achieved. The adsorptive stripping response was evaluated with respect to electrolyte, solution pH, accumulation time, concentration dependence and other variables. A linear peak current-concentration relationship was observed up to 1 microgram ml-1 of chlorprothixene; the relative standard deviation (at the 0.6 microgram ml-1 level) is 3.2%. For a preconcentration time of 10 min, the detection limit was found to be 2 ng ml-1. The open circuit preconcentration/medium exchange/voltammetric scheme was used to eliminate interference from sample solutions. The application of the method to human urine samples is described. PMID- 1928737 TI - Indirect determination of free cyanide in industrial waste effluent by atomic absorption spectrometry. AB - An indirect method is described for the determination of free cyanide in industrial waste effluent samples by atomic absorption spectrometry (AAS). In an alkaline medium, cyanide forms a stable complex species [Cu(BPTC)(CN)] (BPTC = 2 benzoylpyridine thiosemicarbazone), which can be extracted into a mixture of isobutyl methyl ketone-isopentyl alcohol (7 + 1) with an efficiency of greater than 98.5%. The extract can be analysed directly for copper (and hence indirectly for cyanide) by flame AAS. The calibration graph is linear up to 5.7 micrograms of cyanide per millilitre of solvent mixture and the limit of detection is 4.8 ng ml-1. A large number of foreign ions were found not to interfere with the proposed method. PMID- 1928736 TI - Flame atomic absorption spectrometric method for the determination of beryllium in natural waters after separation with N-benzoyl-N-phenylhydroxylamine. AB - A procedure for the determination of beryllium in natural waters is proposed. A solvent extraction step was performed in order to overcome interferences and isolate beryllium before it was atomized by direct nebulization of the organic phase in a dinitrogen oxide-acetylene flame. N-Benzoyl-N-phenylhydroxylamine was used as the extractant whilst isobutyl methyl ketone was the organic solvent. The effects of pH, amine concentration in the organic phase, shaking time, stability of the complex and nature of the extracted species were studied. The detection limit and linear response range are 2 ng ml-1 and 0-1.0 microgram ml-1, respectively. The result obtained for a standard reference material compared well with the quoted value. PMID- 1928738 TI - Determination of nickel in water by chemiluminescence. AB - The acetone chemiluminescence determination of nickel in water was investigated. Optimization data for the determination of Ni2+ and interference data for over 20 species are provided. The limit of detection for Ni2+ by this method is 2.5 ng ml 1, and the linear dynamic range is from 10 ng ml-1 to 1 microgram ml-1. The application of the method to the determination of Ni2+ in river and waste waters is discussed. PMID- 1928739 TI - Nitrogen factors for pork: a reassessment. Analytical Methods Committee. AB - The nitrogen factor (the percentage of fat-free nitrogen in a sample) for pork was estimated from a sample of 60 carcases from four commercial abattoirs. The sample included carcases defined as pork weight (52 +/- 2 kg), bacon weight (72 +/- 4 kg) and heavy weight pigs (92 +/- 8 kg). The nitrogen factor for the lean with intermuscular fat in the whole side was 3.50 (estimated for the national average pig used for processing). Comparable figures for joints were 3.49 (leg), 3.38 [neck (collar)], 3.42 (hand), 3.66 (loin) and 3.50 (belly). These factors are similar to those published by the Analytical Methods Committee in 1986 but are based on a larger sample more representative of the current pig population in Britain. It is recommended that they now become the basis for the standard factors. As factors change significantly with the mass of carcase and fatness, it will be appropriate to revise the estimates as the average national pig population changes. Fat, moisture, ash, hydroxyproline and nitrogen contents in each joint and the side are also reported in this paper. PMID- 1928740 TI - Ganglion formation from the otic placode and the otic crest in the chick embryo: mitosis, migration, and the basal lamina. AB - We have studied the morphogenesis of the cochleo-vestibular (CVG) and distal cranial ganglia in the early chick embryo (White Leghorn embryos). Light microscopy and immunocytochemical staining for fibronectin and laminin were used to trace the cellular contributions to these ganglia from the otic placode and otocyst. Serial semi-thin plastic sections (3-5 microns) stained with toluidine blue at each Hamburger-Hamilton stage (St.) from 10 to 21 were used. We were able to trace individual groups of cells derived from these epithelial structures into the anlagen of the CVG and the distal parts of cranial n. ganglia VII, IX, and X. For immunostaining, antisera were used to visualize the basal lamina in 15 microns cryostat sections from St. 14 to 21 embryos. Described here for the first time is the otic crest, a ridge of epithelium surrounding the placode. Cells migrate from the otic crest (St. 11 to 14) during the period when the otocyst is forming. These cells become continuous spatially with those derived from the epibranchial placodes and the presumptive ganglia of cranial nerves VII, IX, and X. Furthermore, rostral otic crest cells merge with neural crest cells, which appose the myelencephalon, and they join with the newly formed neuroblasts of the CVG, which migrate from the ventral epithelium of the otocyst at St. 14 to 21. This region of the epithelium forms the bulk of the CVG; it also has many more mitotic figures than the rest of the otocyst. Cells in the rostralmost CVG (vestibular part) are the first to complete their migration and send axons into both the medulla and incipient crista ampullaris. Immuno-staining for fibronectin and laminin shows that these two basal-lamina-associated glycoproteins appear in a continuous layer beneath the otic epithelium just prior to CVG migration. Thus there is no evidence that the migration is launched by a prior decomposition of the basal lamina. The cells migrating from the epithelium bridge the basal lamina with their leading processes while the trailing processes are withdrawing from the epithelium. These trailing processes must withdraw after the neuroblast migrates, since most of the neuroblasts undergo mitosis in subsequent stages. The migrating cells appear to push out of the epithelium by displacing immunostained fragments of the basal lamina ahead of their leading processes. This suggests that the exodus of cells is accompanied by forces within the epithelium itself. Whether this is generated by the migratory neuroblasts themselves or by other sources remains to be determined. PMID- 1928741 TI - Limits to the dependence of developing neurons on protein synthesis in their axonal target territory. AB - Our basic question was whether the survival of developing neurons is critically dependent on the level of protein synthesis in the axonal target region. The experiments were carried out on the projection from the isthmo-optic nucleus (ION) to the contralateral retina in chick embryos. The ION is known to undergo almost 60% neuronal death between embryonic days (E) 12 and E17 and to be critically dependent on the retina for trophic support throughout this period and shortly afterwards. Various concentrations of the protein synthesis inhibitor cycloheximide were infused into one eye from E15 to E19. Moderate inhibition (up to about 40%) of retinal protein synthesis, which did not lead to retinal degeneration, had no detectable effects on the number of neurons, nor on the general morphology, in the ION. Only when the inhibition was as high as 50%, leading to widespread degeneration in the retina, did massive degeneration occur also in the ION. It was also shown that a single intraocular injection of cycloheximide at E15 that inhibited retinal protein synthesis by as much as 70 90% during the subsequent 24 h had little effect on the ION in embryos fixed at E19. These results indicate that although the ION neurons are critically dependent on the retina, they can resist major reductions in the level of retinal protein synthesis, which argues against the widespread belief that neuronal survival during development is regulated by the limited production of trophic molecules in the axonal target area. The data are, however, compatible with alternative hypotheses. Most plausibly, survival may be regulated by limited access to a nonlimiting supply of trophic molecules. PMID- 1928742 TI - Development of AChE-positive, NA-containing and VIP- and NPY-immunoreactive nerves in the major cerebral arteries of the rat. AB - The development of cerebrovascular nerves containing noradrenaline (NA), acetylcholinesterase (AChE), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) was studied in rats from before birth to adulthood. All these nerves entered the cranial cavity along the cerebral carotid, internal ethmoidal, and vertebral arteries during the early stages of development, but the subsequent growth and distribution of NA-containing and NPY-immunoreactive (IR) nerves differed greatly from that of AChE-positive and VIP-IR nerves. NA-containing and NPY-IR nerves extended rapidly from the cerebral carotid artery and spread over all the major arteries of the internal carotid system by postnatal day 3, as well as descending the posterior ramus of the cerebral carotid to mingle with nerves from the vertebral artery around the mid-basilar artery by day 5. AChE-positive and VIP-IR nerves from the internal ethmoidal artery covered the whole internal carotid system during the first postnatal week, and projected to the upper basilar artery after the second week, while those from the cerebral carotid artery remained limited to the middle cerebral artery throughout development. By day 21, all major arteries of the internal carotid system had dense plexuses of the four nerve types that were similar to those observed in adult rats. The vertebrobasilar system also had a well-organized network of NA-containing and NPY IR nerves, but only a poor supply of AChE-positive and VIP-IR nerves. Even on day 30, the latter two nerve types were sometimes absent from the middle to caudal basilar artery, owing to a lack of interdigitation by nerves from the internal ethmoidal and vertebral arteries. PMID- 1928743 TI - Endothelial heterogeneity in the chick wing bud: a morphometric study. AB - The microvascular endothelium of the chick wing bud at stages 22, 27, and 32 was evaluated by ultrastructural morphometry. The rationale for this study is based on the hypothesis that endothelial cells exhibit variation in structure and function during cytodifferentiation. The microvessels had a luminal diameter range such that they were classified as capillaries. The thin continuous endothelium was devoid of a basal lamina. The endothelium had a very small number of plasmalemmal vesicles; vacuoles were however present for all stages and in some cases were abundant. The temporal findings were that endothelial cell thickness increases, plasmalemmal vesicle densities decrease, and the densities of cytoplasmic vacuoles increase. The spatial results were that endothelial cells in proximal regions of the limb have a greater thickness, contain fewer vesicles and have more vacuoles than those in distal regions. In general, these results indicate that endothelial ultrastructural heterogeneity occurs within a 3 1/2 day time-span of wing bud development. The discussion considers the results with regard to recent reports on endothelial cell heterogeneity. PMID- 1928744 TI - Development of floor plate, neurons and axonal outgrowth pattern in the early spinal cord of the notochord-deficient chick embryo. AB - The notochord is probably involved in the development of the neural tube. In this study, a fragment of caudal notochord was extirpated in ovo from chick embryos at 1.5 days of incubation. At 4.5 days a distinct notochord-deficient region at thoracolumbar level was found. Profound effects were seen, especially at the cranial site of this region. Somites were smaller than normal, or even not recognizable, and in some cases the myotomes were fused in the midline. The spinal cord appeared reduced in size and lacked a floor plate. The average amount of spinal cord neurons was 23% of the normal value, the cells being located circularly along the outer margin of the spinal cord, except for the roof plate. Axonal roots left the cord in the ventral midline only. Caudal to this site, neurons or floor plate cells were alternately present in the ventral spinal cord, and axonal roots left bilaterally. In a caudal direction, a normal morphology gradually reappeared. The possibility is discussed that reduction in spinal cord size and amount of neurons is a direct or indirect effect of the absence of the notochord, and that the sclerotome may be involved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928745 TI - Myocardial capillaries: increase in number by splitting of existing vessels. AB - To study myocardial vascular development, stereological parameters were estimated in 24 Wistar rat hearts of six different age groups, from newborn to adult. The vascular surface density showed a sharp increase in the first 2 weeks, a peak around the age of 2 weeks, and then a steady decrease until it flattened in adulthood. In contrast, the vascular volume percentage, when plotted against age, decreased continuously with the greatest change in the first week, after which the curve flattened. These findings are compatible with an increase in the number of capillaries with a concomitant decrease of their diameters. Qualitative scrutiny of the histology did indeed support the idea that vessels become thinner. Reconstructions of the histological sections showed the same change three dimensionally. The reconstructions also demonstrated very small holes that seemed to go through the capillaries in the younger stages. Corrosion casts of the blood vessels were made using a casting resin. This was injected into the umbilical artery of rat embryos from 15 days gestation to birth. In postnatal rats of six age groups methacrylate was injected directly into the left ventricle. These casts supported the stereological data by showing an increase in number and decrease in diameter of capillaries, while during pre- and postnatal development, the intervascular spaces lengthened from small, irregular spaces to long, rectangular ones. Small holes, the probable precursors of such spaces, were clearly visible in the wider vessels of the youngest stages. All data point to an interesting mode of capillary growth, i.e. growth by division of existing vessels. PMID- 1928746 TI - Microglia in tadpoles of Xenopus laevis: normal distribution and the response to optic nerve injury. AB - We have studied the distribution of microglia in normal Xenopus tadpoles and after an optic nerve lesion, using a monoclonal antibody (5F4) raised against Xenopus retinas of which the optic nerves had been cut 10 days previously. The antibody 5F4 selectively recognizes macrophages and microglia in Xenopus. In normal animals microglia are sparsely but widely distributed throughout the retina, optic nerve, diencephalon and mesencephalon (other regions were not examined). After crush or cut of an optic nerve, or eye removal, there occurs an extensive microglial response along the affected optic pathway. Within 18 h an increase in the number of microglial cells in the optic tract and tectum can be detected. This response increases to peak at around 5 days after the lesion. At this time the nerve distal to the lesion contains many microglial cells; the entire optic tract is outlined by microglia, extended along the degenerating fibres; and the affected tectum shows a heavy concentration of microglia. This microglial response thereafter decreases and has mostly gone by 34 days. We conclude that the microglial response to optic nerve injury in Xenopus tadpoles starts early, peaks just before the regenerating optic nerve axons enter the brain, and is much diminished by the time the retinotectal projection is re established. The timing is such that the microglial response could play a major role in facilitating regeneration. PMID- 1928747 TI - Immunolocalization of epidermal growth factor (EGF), EGF receptor and transforming growth factor alpha (TGF alpha) during murine palatogenesis in vivo and in vitro. AB - The distribution of epidermal growth factor, the epidermal growth factor receptor and transforming growth factor alpha during murine palatogenesis was investigated immunocytochemically. On embryonic day 12 staining for transforming growth factor alpha was present throughout the palatal mesenchyme, with little in the epithelia. On embryonic day 13 staining increased in the palatal epithelia and in the mesenchyme at the tip of the palate. As the palatal shelves fused together (embryonic day 14.5) intense staining for transforming growth factor alpha was seen in the midline epithelial seam and in the subjacent mesenchyme. On embryonic day 15 there was a generalised increase in palatal epithelial staining; this was most marked in the remnants of the degenerating epithelial seam. Mesenchymal staining was, however, uniform. Whilst palatal staining for epidermal growth factor was sparse, at all stages, staining for its receptor was present throughout the palatal epithelia and mesenchyme. This was most intense in the palatal medial edge epithelia at the time of midline epithelial seam degeneration. The regional and temporal differences in staining for the epidermal growth factor receptor and transforming growth factor alpha suggested that these molecules may play an important role in normal palate development in vivo, particularly in degeneration of the midline epithelial seam. PMID- 1928748 TI - Local effects of impaired mechanical properties of collagen on bone formation and resorption. AB - To study the relationship between the mechanical properties of collagen and the bone turnover, 2-week-old Balb/C mice were fed on a diet containing 0.25% Beta aminopropionitrile (B-APN), a potent inhibitor of collagen crosslink formation, for 3 weeks. Mandibular incisor socket was selected for the analysis of bone formation and resorption parameters. Plastic embedded sections stained with toluidine blue and cut at 4 microns were used to analyze the average area of bone lamellae, bone-forming surface, and the number of osteoblasts/mm of forming surface. Similar sections were used to localize acid phosphatase on resorbing surfaces and within the osteoclasts, while bone alkaline phosphatase was determined by a colorimetric method. Morphometric analyses showed that the area of newly formed bone lamellae, total forming surface, number of osteoblasts and the Alk. Pase activity were significantly lower in B-APN-fed mice as compared to the controls. There was a concomitant smaller, but significant, reduction in total resorption surface, active resorption surface and the number of osteoclasts. These results suggest that the regulation of bone formation and resorption at this site, which is independent of systemic regulation, is influenced by the mechanical properties of the collagenous matrix, which in turn may have a significant effect on the existing pool of bone-forming cells, but may not influence the recruitment of new cells. PMID- 1928749 TI - The efferent projections of neurons in the white matter of different cortical areas of the adult rat. AB - Injection of Fast Blue into different cortical areas (frontal, parietal, anterior and posterior cingulate cortex) revealed that neurons in the white matter (interstitial neurons) give rise to association fibers which project mostly to the gray matter of the overlying cytoarchitectonic area, but which may extend also over different cytoarchitectonic areas. The rostrocaudal extent of the projecting axons was up to 1 mm in the frontal and parietal cortex, and up to 3.5 mm in the cingulate cortex. Concurrent processing for dihydronicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry showed that 70% of cortically projecting interstitial neurons were NADPH-d-positive. An analysis of neuronal morphology suggests that the FasT-Blue-labeled, NADPH-d-negative neurons may represent displaced pyramidal neurons of layer VIb; the Fast-Blue-labeled and NADPH-d-positive neurons have bipolar or multipolar dendritic trees, constituting a population of nonpyramidal interstitial neurons that project into the cortical gray matter. PMID- 1928750 TI - A contribution with review to the description of mineralization of bone and other calcified tissues in vivo. AB - This manuscript considers certain aspects of mineral deposition in bone and other vertebrate calcifying tissues in order to examine physical, chemical, and biological factors important in the mineralization process. The paper in a discussion format principally presents a new data and the formulation of concepts based on such data as well as a summary of background material as necessary review. Mineralization is found to occur at spatially independent sites throughout the organic extracellular tissue matrices. Matrix vesicles and collagen fibrils each may serve as independent nucleation centers for mineral with vesicle mineralization being local and collagen mineralization dominating the tissues as a whole. Collagen fibril organization is suggested to be such that hole zones are aligned in three dimensions, creating extensive channels for mineral accommodation. Nucleation occurs initially in hole zones and crystal growth leads to the development of plate-like mineral particles whose orientation, disposition, and sizes within fibrils are detailed. Effects of diffusion, crystallinity, and critical nucleation and growth events are described with respect to their influence on mineral deposition in bulk and local regions of tissue matrices. PMID- 1928751 TI - Occurrence of bioactive and immunoreactive inhibin (13 KD) in human epididymis. AB - Using specific polyclonal antibodies generated against a 13 KD human testicular inhibin, immunocytochemical localization of inhibin was carried out in different regions of human epididymis. The concentrations of inhibin were greater in caput and corpus regions as compared to the caudal region. The epididymal inhibin was found to be bioactive, since it suppressed specifically the FSH levels of rat pituitaries in vitro. Spermiophage/macrophage cells exhibited strong staining for inhibin which were suggestive of a possible role of inhibin in modulation of immune function. In view of the known activities of inhibin in cellular growth, differentiation, and steroidogenesis, epididymal inhibin could have a role in acquisition of sperm fertilizing capabilities. PMID- 1928752 TI - Evidence for the presence of actin-associated intercellular adhesion junction between interstitial cells of Leydig in the ground squirrel testis. AB - Interstitial cells of Leydig characteristically occur in clusters around blood vessels. Often these clusters remain intact when interstitial tissues are mechanically separated from other components of the testis. The presence of strong intercellular attachments is most likely one of the factors responsible for maintaining the integrity of Leydig cell clusters. In many tissues, actin associated adhesion junctions commonly provide intercellular attachment. To determine if actin associated adhesion junctions are present between Leydig cells, we have used 1) immunofluorescence to probe for two components that characterize these junctions in other tissues and 2) electron microscopy to examine areas of intercellular contact for evidence of microfilament related adhesion junctions. Isolated clusters of unsectioned cells, which had been fixed and detergent extracted, were probed with the F-actin specific strains rhodamine phalloidin and NBD-phallacidin and with an affinity purified primary antibody raised against human platelet vinculin. In regions of intercellular contact, fluorescence staining with the actin probes was intense and appeared as a solid linear band. Similar regions also stained with the vinculin probe. In double label experiments, actin and vinculin probes were co-distributed at sites of intercellular contact. Zones of intercellular contact, apparently similar to those detected with fluorescence microscopy, were observed at the ultrastructural level. At these sites, subsurface filaments, interpreted by us as actin, formed a dense carpet adjacent to the plasma membrane on each side of the junction. These filaments appeared to be organized into networks rather than discrete bundles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928753 TI - Localization of calmodulin in perinuclear structures of spermatids and spermatozoa: a comparison of six mammalian species. AB - The distribution of Calmodulin was examined during spermiogenesis and sperm epididymal maturation in rabbit, hamster, mouse, rat, monkey, and human. An affinity-purified antibody to Calmodulin was used to characterize this protein in sperm extracts by immunoblot analysis. Post-embedding immunogold procedures were used to localize Calmodulin at the ultrastructural level. The pattern of Calmodulin distribution was similar in the six species studied. A diffuse labeling was observed in round spermatids. Gold particles accumulated first in the subacrosomal layer of elongating spermatids. The perinuclear ring was also labeled. During the maturation phase of spermatids, Calmodulin labeling extended to the postacrosomal sheath. Dramatic changes occurred at spermiation so that in testicular sperm Calmodulin immunostaining was predominant in the postacrosomal sheath. Some labeling was still detected in restricted areas of the subacrosomal layer. This feature varied from species to species. Calmodulin location did not change during sperm epididymal maturation. A role for Calmodulin in the control of manchette development and regulation of subacrosomal actin aggregation state during spermiogenesis is proposed. The unique location of Calmodulin in the postacrosomal sheath of all species that have been studied in this work, together with the known presence of calcium in this area suggest a pivotal role for Calmodulin in sperm-egg fusion process. PMID- 1928754 TI - Origin and distribution of perforatorial proteins during spermatogenesis of the rat: an immunocytochemical study. AB - The perforatorium is the subacrosomal portion of the perinuclear theca that encapsulates the nucleus of spermatozoa. In the rat, the perforatorium is a curved pointed structure, which in cross section is triangular in outline over the apical half and beyond the tip of the nucleus. The perforatorium, composed of several proteins, appears as a distinct structural entity only at the very end of spermiogenesis. In this study, polyclonal antibodies prepared against the entire isolated perforatorial fraction and against the major 16 and 34 kDa perforatorial polypeptides were used to determine the distribution of perforatorial proteins in germinal cells at various steps of differentiation. Immunoperoxidase staining at the LM level and quantitative immunogold labeling at the EM level were used. The labeling patterns with all three antibody preparations were identical. The immunolabeling first appeared in early pachytene spermatocytes and increased progressively, with a statistically significant upward trend, in both the nuclei and cytoplasm of spermatocytes and spermatids until step 9 of spermiogenesis. Up to this step the labeling concentration was significantly higher over the nucleus than over the cytoplasm. During nuclear condensation in steps 9 and 12 spermatids, there was a progressive loss of all the labeling over the nucleus and a corresponding increase of labeling over the cytoplasm. During steps 16-18, the early signs of condensation of perforatorial proteins occurred next to the inner acrosomal membrane. Then during step 19 there was a sudden condensation of perforatorial proteins into a definitive perforatorium. Thus proteins destined to form this cytoskeletal structure reside in both the nucleus and cytoplasm of spermatocytes and spermatids until nuclear condensation of the latter. Thereafter, they are restricted to the spermatid's cytoplasm and finally condense around the elongated nucleus at the end of spermiogenesis. PMID- 1928755 TI - Glycoconjugate histochemistry of Xenopus laevis fundic gland with special reference to mucous neck cells during development. AB - Mucous neck cells (MNCs) of the fundic gland are phylogenetically thought to have first appeared in amphibians. We studied the origin and differentiation of MNCs in fundic glands of Xenopus laevis. By means of lectin histochemical methods using Griffonia simplicifolia agglutinin-II (GSA-II), MNCs were detected specifically in fundic glands of adult X. laevis. Mucous granules of MNCs were labeled by GSA-II-colloidal gold (CG) staining. Other cells such as surface mucous cells (SMCs), oxynticopeptic cells (OPCs), and endocrine cells did not react to GSA-II. Ulex europaeus agglutinin-I specifically stained OPCs, but not MNCs and SMCs. During the morphogenetic period of the stomach in metamorphosing larvae, GSA-II reactive cells randomly appeared in various portions of the underdeveloped fundic glands and then rapidly localized in the neck portion. At this time, newly appearing mucous granules of MNC type were labeled by GSA-II-CG. Two types of cells intermediate to MNCs and SMCs and intermediate to MNCs and OPCs were observed in the larval gastric region. Cells intermediate to MNCs and OPCs were also found in adults. In these cells, mucous granules of MNC type were labeled by GSA-II-CG, but mucous granules of SMC type and zymogen-like granules did not react to GSA-II. These observations suggest that GSA-II is a useful marker in studying the differentiation of MNCs and their precursors regardless of species differentiation. PMID- 1928756 TI - Intracellular variation of rat intestinal mucin granules localized by monoclonal antibodies. AB - Monoclonal antibodies produced against rat small intestinal mucins were utilized to study variability of stored mucin granules within rat ileal goblet cells. Eleven antibody-secreting hybridoma cultures were produced; six of these uniformly labeled stored mucin granules in virtually all goblet cells, suggesting that some antigenic features are common to all granules. The other five stained goblet cells in the rat small intestinal epithelium nonuniformly. R803, R805, and R807 localized within almost all goblet cells but revealed differential labeling of centrally and peripherally located mucin granules. R804 uniformly labeled the mucin granules of most villous goblet cells; some of the crypt goblet cells were uniformly labeled, but the majority were only partially labeled, resulting in a mottled staining pattern. R808 stained only a small portion of crypt goblet cells; there is, however, an increase in both number of goblet cells labeled and in uniformity of staining of the stored granule mass from the base of the crypt to the surface, resulting in uniform labeling of virtually all goblet cells at the villus tip. This study demonstrates for the first time that rat small intestinal mucin granules are immunologically heterogeneous and nonuniformly distributed within the epithelium. Additionally, staining patterns within the stored granule mass suggest that structurally distinct subpopulations of mucin granules may exist within a single goblet cell. PMID- 1928757 TI - Changes in immunoreactivity for cathepsin H in rat type II alveolar epithelial cells and its proteolytic activity in bronchoalveolar lavage fluid over 24 hours. AB - Variations in immunoreactivity for cathepsin H in rat type II alveolar epithelial (type II) cells and in its proteolytic activity in bronchoalveolar lavage fluid (BALF) were examined at six evenly spaced times over 24 hr (light period: 0600 1800 hr). Ring-shaped immunodeposits for cathepsin H were detected in type II cells (lamellar bodies), their sizes varying over 24 hr. The large ring-shaped immunodeposits increased during the light period, decreasing rapidly from 2000 to 0000 hr. Small intense immunodeposits abundantly appeared in the cells at 0000 hr. The area densities of immunodeposits in type II cells and their optical densities also varied with the time of day; both densities were high during the dark period, peaking at the mid dark period, whereas they were decreased during the light period. Proteolytic activities of cathepsin H in BALF (6 ml/rat) examined at each time revealed a distinct variation over 24 hr, corresponding to the variation in the immunoreactivity in type II cells. The activities in BALF were high from 1600 to 0400 hr and low at 0800 hr. These results suggest that the variation in immunoreactivity for cathepsin H in type II cells over 24 hr reflects the intracellular growth of lamellar bodies and secretory activity of the cells. Similar variations in the immunoreactivity and proteolytic activity of cathepsin H in the cells and BALF indicate its cosecretion with surfactants. PMID- 1928758 TI - Morphological analysis of the cellular interaction between thymocytes and a thymic stromal cell line (TEL-2). AB - In a previous study (Nakashima et al., Eur. J. Immunol., 20: 47-53, 1990), a cloned stromal cell line TEL-2 was established from Balb/c mouse thymus. Incubation of thymocytes with TEL-2 cells resulted in the selective elimination of CD4 and CD8 double-positive thymocytes from the culture. In the present report, both phase-contrast and scanning electron microscopes were used to examine, at various time intervals, TEL-2 cells cocultivated with thymocytes in order to elucidate the kinetic sequence of their cellular interaction. The thymocytes attached to the TEL-2 cell surface were more numerous at early times (30 min to 1 h), and their number decreased gradually with time. In contrast, the thymocytes that migrated into the TEL-2 cell layers were less abundant at early times, their number increasing with time thereafter. Destruction of the regular arrangement of TEL-2 cells was found at later than 1 h, suggesting active cellular interaction. The thymocytes adherent to the TEL-2 cell surface were found to be of various shapes and often showed variable profiles, e.g., extending small cytoplasmic processes along the surface of TEL-2 cells or appearing ameboidal. A remarkable feature of the TEL-2 cells was that they formed numerous "round spaces" at the surface of the TEL-2 cell layers. The thymocytes were often located around "round spaces," and some were seen migrating into TEL-2 cell layers through these round spaces. In addition, complementary examinations by transmission electron microscopy revealed that the internalization of thymocytes into TEL-2 cells occurs inside the TEL-2 cell layers after migration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928759 TI - Anatomic distribution of autonomic neural tissue in the developing dog heart: II. Nonadrenergic noncholinergic innervation by calcitonin gene-related peptide immunoreactive tissue. AB - We used immunocytochemical localization of calcitonin gene-related peptide (CGRP) to trace the ontogenesis and anatomic distribution of this component of nonadrenergic noncholinergic (NANC) innervation in fetal, neonatal, and mature canine hearts and autonomic ganglia which control cardiac function. Rare varicose CGRP-immunoreactive nerve processes were present in the heart during late gestation. Abundant CGRP-immunoreactive neural tissue in the neonate suggested a burst of NANC innervation around birth. Neonatal, 1-, and 2-month-old animals all had many varicose individual nerve processes in addition to processes within bundles; however, the density of all CGRP-immunoreactive tissue appeared to decrease during this stage of development. Similarly, there were relatively more varicose stained nerve processes in the epicardial ganglia and numerous CGRP immunoreactive cells and smooth nerve processes in the stellate ganglia of the neonate, as compared with older animals. In the mature animal CGRP-immunoreactive neural tissue in the heart was more sparse and largely confined to heterogeneous nerve bundles in the epicardium. The extramural coronary arteries were virtually the only site of innervation by individual nerve processes; CGRP-immunoreactive neural tissue was not found adjacent to working cardiac muscle fibers. At all developmental stages, the area of the sinoatrial node was the primary focus of CGRP innervation, although the atrioventricular nodal region was also preferentially innervated. In general, the atria contained more CGRP immunoreactive tissue than the ventricles, which were only sparsely innervated. The perinatal peak in density of CGRP-immunoreactive neural tissue with subsequent decline to reach the adult pattern suggests a developmental role for NANC innervation in the dog heart. PMID- 1928760 TI - Further evidence of the presence of rat embryonic hypothalamic factors that induce the differentiation of gonadotrophic hormone-releasing hormone-containing secretory neurons. AB - We examined the presence of factor(s) in the embryonic medial basal hypothalamus (MBH) that may influence nasal placode (NAP)-derived luteinizing hormone releasing hormone (LHRH) neurons in determining their secretory phenotype. In this study, we performed organotypic culture and transplantation of the NAP from 12.5-day-old embryos of rats and vomeronasal organ (VNO) from 14.5-day-old embryos. Surgical operations, however, were performed on 16.5-day-old embryos. The NAP and VNO were cultured singly or with the MBH obtained from the embryos of the same age and, further, in a medium with a nerve growth factor or fibroblast growth factors. Although LHRH neurons were derived from the NAP and VNO in all the cultures, judging from numbers and cellular morphologies, the MBH was most effective. The VNO was transplanted into the third ventricle of adult female rats singly or with the cerebral cortex, the mesencephalon-myelencephalon complex, or the MBH from 14.5-day-old embryos. All the grafts gave rise to LHRH neurons, but the number of the neurons was far greater in the grafts cotransplanted with the MBH, in which the neurons projected long processes to blood capillaries and formed neurovascular complexes, the feature of which may suggest the occurrence of the secretory activity in the fibers. The animals were examined 5 days after the surgical operations. In rhinoectomized embryos, LHRH neurons were distributed throughout the brain in the same pattern as found in intact rats, showing normal cellular morphology. In the encephalectomized rats, immunoreactive LHRH cells were present only in the terminal ganglia. These findings indicate that the embryonal MBH has a factor (s) that is essential to the development of secretory LHRH neurons. PMID- 1928761 TI - Effect of basicranial flexion on larynx and hyoid position in rats: an experimental study of skull and soft tissue interactions. AB - The mammalian upper respiratory tract is a functionally dynamic region involved in respiration, deglutition, and phonation. As the structures of this area (e.g., larynx, hyoid) are suspended from the basicranium, changes in basicranial shape may affect both their anatomy and function. Although skeletal/soft tissue relationships have been examined through descriptive, comparative anatomy, these relationships have remained largely unexplored via experimental study. In this study, mechanical relationships between basicranial shape and positions of the larynx and hyoid bone are investigated experimentally. Skull base flexion was induced by surgically ablating the spheno-occipital synchondrosis in 13-day-old rats. Lateral radiograms were taken at 40, 60, 80, 100, and 120 days, and angular measurements made of basicranial shape and positions of the larynx and hyoid bone. Statistical analysis shows significant differences between experimental and control groups for skull base, hyoid, and larynx angles, and negative (inverse) correlations for basicranial shape change vs. hyoid position, and basicranial shape change vs. larynx position. Results show induced basicranial flexion caused inferior displacement of the larynx and hyoid bone, thus indicating a direct, mechanical relationship between skeletal and soft tissues. These observations may aid in understanding the basic biological, pathological, and evolutionary interactions of hard and soft tissues of the upper respiratory region. PMID- 1928762 TI - Relationship between the articular surface area of a bone and the magnitude of stress passing through it. AB - The present study investigates the relationship between the articular area of a bone and the magnitude of the stress it resists. An attempt was also made to find the correlation between the development of a bone and its articular area. The material of the study consisted of a large number of dry, macerated, adult male skeletons. The articular surface area of the bones was measured with the help of a planimeter. The magnitude of the force acting on the proximal articular surface of a bone is expected to go out of the bone through its distal articular surface in almost the same proportion. The present investigation is based on the assumption that if the articular area is related to the magnitude of stress, then the proximal and distal articular areas of a bone should also be correlated. A significant correlation was observed between the proximal and distal articular areas of axis vertebra; L4 and sacrum; and tibia-fibula and talus. This indicated that the stress resisted by proximal and distal articular areas was in the same proportion. Similarly, a significant positive correlation between bone index and articular area in ribs, tibia, and laminae of vertebrae indicated that the bone mass (development) runs parallel to the articular area. Thus, the present investigation could reveal that the articular area and bone development are related to the stress acting on the bone. PMID- 1928763 TI - The "not-so-educated hand" of the pediatric anesthesiologist. PMID- 1928764 TI - Central thermoregulatory inhibition by general anesthesia. PMID- 1928765 TI - ASA Award: John F. Nunn. PMID- 1928766 TI - Effect of intraoperative low-dose dopamine on renal function in liver transplant recipients. AB - Patients undergoing orthotopic liver transplantation frequently receive dopamine infusions to preserve renal function. To test the benefit of such infusions on renal function, 48 nonanuric patients presenting for OLT were entered into a randomized double-blind protocol. After exclusion of 1 patient for intraoperative nephrectomy, 22 patients received dopamine at a rate of 3 micrograms.kg-1.min-1 during surgery and the first postoperative 48 h, and a control group of 25 patients received saline. Venovenous bypass was used in 45 of 47 patients. During the hepatic vascular anastomoses, the donor liver was flushed with cold saline. In 7 patients, the flush contained mannitol (50 g) as part of a surgical protocol to investigate its role as a potential free radical scavenger. Initially, it appeared that there was an increase in urine output during the neohepatic phase in those patients receiving dopamine versus controls (4.20 +/- 3.3 vs 2.10 +/- 1.3 ml.kg-1.h-1, respectively). Upon further statistical analysis, this increase was associated with inclusion of mannitol in the liver flush of 5 patients in the dopamine group. After excluding all patients receiving flush containing mannitol, there was no significant difference in urine output during the neohepatic phase between the dopamine group and controls (2.94 +/- 0.45 and 2.10 +/- 0.28 ml.kg 1.h-1, respectively). The glomerular filtration rates at 1 month after surgery were similar and decreased approximately 40% in each group. Although a beneficial effect of dopamine in all situations cannot be ruled out the authors conclude that routine perioperative use of dopamine is of little value in nonanuric patients presenting for orthotopic liver transplantation. PMID- 1928767 TI - Postoperative analgesia by intravenous clonidine. AB - Clonidine, an alpha 2 adrenoreceptor agonist, has nonopiate antinociceptive properties, which might be an alternative for postoperative analgesia free of opioid-induced side effects. To document the analgesic properties of intravenous clonidine during the postoperative period, 50 ASA physical status 1 patients, immediately after spinal fusion, were randomly assigned to two groups, blindly administered either clonidine (5 micrograms/kg infused the 1st h and then 0.3 microgram-1.kg-1.h-1 during 11 h) or a placebo. A visual analog scale graded from 0 (no pain) to 100 mm was used to assess pain before clonidine or placebo administration (T0), at the end of the loading dose (T1) and then every 2 h (T3, T5, T7, T9, and T11). Morphine (0.1 mg/kg) was administered intramuscularly after each pain measurement if the score was greater than 50 mm. No morphine was given at T0. Hemodynamics, blood gases and plasma clonidine concentrations were measured each time the pain score was measured. The pain score decreased from 42 +/- 5 to 26 +/- 3 mm (mean +/- standard error) in the clonidine group whereas it was unchanged in the placebo group despite a greater morphine requirement (dose for each patient: 3.8 +/- 1 vs. 10.8 +/- 1.2 mg). Clonidine delayed the onset of pain and the first request for morphine injection. Mean arterial pressure decreased to 74 +/- 2 mmHg in the clonidine group (-26 +/- 2 vs. -15 +/- 2% in the placebo group at T11) despite a significant increase in the cumulative fluid volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928768 TI - Intravenous dantrolene does not exhibit calcium channel blocking effects on the cardiac conduction system in humans. AB - In malignant hyperthermia, dantrolene, a drug assumed to possess calcium channel blocking properties, effectively suppresses supraventricular and ventricular arrhythmias. To investigate antiarrhythmic properties of dantrolene, six patients (three women and three men, age 42 +/- 18 yr) with symptomatic atrioventricular (AV)-nodal reentry tachycardia were studied. Electrocardiographic measurements included sinus cycle length, PQ-interval, width of the QRS-complex, and QT- and rate-corrected QT-interval. During the electrophysiologic study, effective refractory periods of the right atrium, AV node, right ventricle, and AV-nodal conduction intervals were determined, and AV-nodal reentry tachycardia was induced in all patients. Dantrolene was administered intravenously over a period of 15 min at doses of 1.0, 1.5, or 3.0 mg/kg in two patients each. The dosage was not further increased because of side effects at the dose of 3.0 mg/kg. After the infusion of dantrolene, the electrocardiographic measurements and electrophysiologic study were repeated. The plasma concentrations of dantrolene ranged from 1.69 to 6.61 micrograms/ml at the time of the electrophysiologic study. After dantrolene administration, the sinus cycle length shortened from 686 +/- 80 to 622 +/- 55 ms (P less than 0.05). No significant changes of any other parameter could be demonstrated after intravenous dantrolene. AV-nodal reentry tachycardia remained inducible in all patients without change of the tachycardia cycle length and without change in coupling intervals of tachycardia-inducing extrastimuli. Antiarrhythmic properties of dantrolene could not be demonstrated in patients with AV-nodal reentry tachycardia at therapeutic doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928769 TI - Physiologic responses to mild perianesthetic hypothermia in humans. AB - To evaluate physiologic responses to mild perianesthetic hypothermia, we measured tympanic membrane and skin-surface temperatures, peripheral vasoconstriction, thermal comfort, and muscular activity in nine healthy male volunteers. Each volunteer participated on three separate days: 1) normothermic isoflurane anesthesia; 2) hypothermic isoflurane anesthesia (1.5 degrees C decrease in central temperature); and 3) hypothermia alone (1.5 degrees C decrease in central temperature) induced by iced saline infusion. Involuntary postanesthetic muscular activity was considered thermoregulatory when preceded by central hypothermia and peripheral cutaneous vasoconstriction. Tremor was considered normal shivering when electromyographic patterns matched those produced by cold exposure in unanesthetized individuals. During postanesthetic recovery, central temperatures in hypothermic volunteers increased rapidly when residual end-tidal isoflurane concentrations were less than or equal to 0.3% but remained 0.5 degree C less than control values throughout 2 h of recovery. All volunteers were vasodilated during isoflurane administration. Peripheral vasoconstriction occurred only during recovery from hypothermic anesthesia, at end-tidal isoflurane concentrations of less than approximately 0.4%. Spontaneous tremor was always preceded by central hypothermia and peripheral vasoconstriction, indicating that muscular activity was thermoregulatory. Maximum tremor intensity during recovery from hypothermic anesthesia occurred when residual end-tidal isoflurane concentrations were less than or equal to 0.4%. Three patterns of postanesthetic muscular activity were identified. The first was a tonic stiffening that occurred in some normothermic and hypothermic volunteers when end-tidal isoflurane concentrations were approximately 0.4-0.2%. This activity appeared to be largely a direct, non-temperature-dependent effect of isoflurane anesthesia. In conjunction with lower residual anesthetic concentrations, stiffening was followed by a synchronous, tonic waxing-and-waning pattern and spontaneous electromyographic clonus, both of which were thermoregulatory. Tonic waxing-and waning was by far the most common pattern and resembled that produced by cold induced shivering in unanesthetized volunteers; it appears to be thermoregulatory shivering triggered by hypothermia. Spontaneous clonus resembled flexion-induced clonus and pathologic clonus and did not occur during hypothermia alone; it may represent abnormal shivering or an anesthetic-induced modification of normal shivering. We conclude that among the three patterns of muscular activity, only the synchronous, tonic waxing-and-waning pattern can be attributed to normal thermoregulatory shivering. PMID- 1928770 TI - Combined epidural and general anesthesia versus general anesthesia for abdominal aortic surgery. AB - The goal of this randomized study of high-risk surgical patients was to determine whether intraoperative thoracic epidural anesthesia in combination with light general anesthesia alters postoperative morbidity when compared to a standard technique of "balanced" general anesthesia. A total of 173 patients scheduled for abdominal aortic reconstruction were admitted to the study; 86 were to receive "balanced" general anesthesia (group 1) and 87 thoracic epidural anesthesia in combination with light general anesthesia (group 2). Preoperative evaluation included standard clinical tools, dipyridamole thallium gammatomography, and radionuclide angiography. In these patients, all of whom had peripheral artery disease, there were no significant differences in associated coronary artery disease, hypertension, and cardiovascular treatment. The distribution of left ventricular ejection fraction and the number of patients with thallium redistribution were not statistically different between the two groups. During the postoperative period, group 1 received analgesia of subcutaneous morphine (n = 35), epidural fentanyl (n = 30), or epidural bupivacaine (n = 21). In group 2, 6 patients with a nonfunctioning epidural catheter due to technical failure received a balanced general anesthesia and were eliminated from the study. During the postoperative period, group 2 received analgesia of subcutaneous morphine (n = 26), epidural fentanyl (n = 25), or epidural bupivacaine (n = 30). Cardiovascular morbidity did not differ between the two groups: 22 patients in group 1 and 19 patients in group 2 had a major postoperative cardiac event.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928771 TI - Hyperventilation reduces transcutaneous oxygen tension and skin blood flow. AB - Transcutaneous oxygen tension (PtcO2) is often used to monitor neonates and infants in special care units and the operating room. The transcutaneous index (TCI = PtcO2/arterial oxygen tension [PaO2]) is known to depend both on age and on cardiac index but is assumed to be independent of other physiologic variables. In this study we have shown that TCI also depends upon arterial carbon dioxide tension (PaCO2). Five young pigs were anesthetized and paralyzed and their lungs mechanically ventilated while they were monitored with PtcO2 electrodes and serial arterial blood gas analyses. For a 45 degrees C PtcO2 sensor, the mean TCI during normocapnia was 0.78, whereas during hyperventilation (PaCO2 = 20 mmHg) the mean TCI was reduced 65%, to 0.27. The corresponding TCI values for a 43 degrees C sensor were 0.33 and 0.065, representing an 80% decrease in TCI during hyperventilation. Hypoventilation had little effect upon TCI as long as hypoxemia was avoided. Twelve awake adult volunteers with radial artery cannulas were monitored with PtcO2 sensors at several body sites and two sensor temperatures. For a 44 degrees C sensor on the chest, the mean TCI decreased from 0.77 at normocapnia to 0.60 at a PaCO2 of 17 mmHg, a 22% change. For the same sensor on the foot, TCI decreased from 0.63 to 0.32, a 49% change. For a 42 degrees C sensor under the same conditions, the corresponding TCI decreases were 51 and 64%. Six of the volunteers were also monitored with laser-Doppler skin blood flow probes located on the chest, hand, and foot.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928772 TI - The effect of halothane on thermosensitive neurons in the preoptic region of the anterior hypothalamus in acutely instrumented cats. AB - Normal thermoregulatory processes are significantly impaired by halothane anesthesia. However, the direct effects of halothane on thermosensitive neurons in the preoptic region of the anterior hypothalamus, a major thermoregulatory site, have not been previously investigated. Thirty-eight cats were anesthetized with alpha-chloralose (60 mg/kg) and urethane (600 mg/kg) and placed in stereotactic restraint. Stainless steel thermodes for highly selective local heating and cooling were stereotactically placed into the preoptic region with thermocouples used to monitor regional temperature. Using tungsten microelectrodes, 148 single neurons in the preoptic region were identified and subjected to local heating (to 42 degrees C) and cooling (to 30 degrees C). Eighteen percent (n = 27) in 15 different cats were classified as thermosensitive by accepted criteria (change in firing rate per degree centigrade of greater than 0.8 spikes.s-1.degrees C-1 or less than -0.6 spikes.s-1.degrees C-1). Thermosensitve units were then subjected to graded concentrations of halothane (0.25-1.0% end-tidal), and local heating and cooling were repeated. The spontaneous firing rate (spikes per second) at 37 degrees C of 21 warm-sensitive neurons was significantly (P less than 0.05) reduced, to 65.5 +/- 8.3, 42.6 +/- 10.7, 28.0 +/- 9.5, and 18.1 +/- 6.0% of control at 0.25, 0.50, 0.75, and 1% halothane, respectively. Spontaneous firing rate returned to 99.5 +/- 19.8% of control within 30 min after discontinuation of halothane. Thermosensitivity (change, per degree centigrade, in spikes per second) was also significantly reduced, to 33.3 +/- 5.6, 28.5 +/- 14.6, and 13.9 +/- 6.6% of control at 0.50, 0.75 and 1.0% halothane (all P less than 0.05 compared to control).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928773 TI - Isoflurane causes only minimal increases in coronary blood flow independent of oxygen demand. AB - Studies on the coronary circulation during halothane or isoflurane anesthesia are conflicting. Also, little attention has been paid to the time course of the effect of these agents on the coronary circulation. Therefore, we investigated the direct and temporal effects of halothane and isoflurane on coronary hemodynamics in chronically instrumented dogs, in the presence and absence of autonomic nervous system blockade. On different days anesthesia was induced via inhalation with 5% halothane or isoflurane in 100% oxygen. After tracheal intubation, anesthesia was maintained at 1.0 MAC for 30 min. Hemodynamics were recorded continuously. Myocardial oxygen consumption was estimated from the pressure-work index. A total of 36 experiments (four sets of experiments) were completed using nine chronically instrumented dogs. Induction of anesthesia with halothane caused a significant (P less than 0.05) increase in coronary blood flow (from 40 +/- 6 to 68 +/- 11 ml/min), which reached a peak at 1.4 +/- 0.3 min. These changes were secondary to increases in heart rate, arterial pressure, and pressure-work index (10.2 +/- 1.4 to 15.9 +/- 0.8 ml O2.min-1.100g-1). With autonomic nervous reflexes eliminated, halothane caused no change in coronary blood flow. Inhalation of isoflurane caused a greater (P less than 0.05) increase in coronary blood flow (from 39 +/- 6 to 85 +/- 14 ml/min) than did halothane; flow reached a peak at 1.8 +/- 0.6 min. With autonomic reflexes eliminated, isoflurane continued to produce an increase (P less than 0.05) in coronary blood flow (from 39 +/- 4 to 53 +/- 5 ml/min), which reached a peak at 2.1 +/- 0.4 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928774 TI - Subarachnoid blockade alters homeostasis by modifying compensatory splanchnic responses to hemorrhagic hypotension. AB - To demonstrate that sympathetic responses transmitted by the splanchnic nerve help maintain intravascular stability, 12 mongrel dogs (35-45 kg each), anesthetized with pentobarbital, were given two separate but identical hypotensive stimuli (mean arterial blood pressure of 60 mm Hg for 15 min) by the withdrawal of appropriate amounts of blood. The first stimulus was performed in the absence of drug or surgical manipulation. The second stimulus was performed after animals were subjected to no intervention (n = 4), bilateral splanchnic nerve section (n = 4), or spinal anesthesia (n = 4). Before and 10 min after the onset of hypotension, arterial epinephrine concentration and adrenal medullary and abdominal organ blood flow were measured. In the group without intervention, the second hypotensive stimulus (like the first) elicited 3-fold increases in adrenal medullary blood flow, 40-fold increases in arterial epinephrine concentration, and a 61% reduction in abdominal organ blood flow (P greater than 0.002). The volume of blood withdrawn to produce hypotension was similar (approximately 21 ml.kg-1). Bilateral splanchnic nerve section attenuated the adrenal medullary blood flow, arterial epinephrine concentration, and abdominal organ blood flow responses to hypotension by 86, 64, and 66%, respectively (P less than 0.008), and the blood volume withdrawn was reduced by 42% (P less than 0.02). Spinal anesthesia eliminated the adrenal medullary blood flow response to hypotension, attenuated the arterial epinephrine concentration and abdominal organ blood flow responses by 78 and 57%, respectively (P less than 0.01), and decreased the blood volume extracted by 55% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928775 TI - Cerebral blood flow response to PaCO2 during hypothermic cardiopulmonary bypass in rabbits. AB - Differences in cerebral blood flow (CBF) between alpha-stat and pH-stat management depend on preserved responsiveness of the cerebral vasculature to changes in arterial carbon dioxide tension (PaCO2). We tested the hypothesis that hypothermia-induced reductions in CBF would decrease the CBF response to changing PaCO2 (delta CBF/delta PaCO2). Anesthetized New Zealand white rabbits were randomly assigned to one of three temperature groups--group 1 (37 degrees C, n = 9); group 2 (31 degrees C, n = 10); or group 3 (25 degrees C, n = 10)--and were cooled using cardiopulmonary bypass. After esophageal temperature equilibration (approximately 40 min), oxygenator gas flows were serially varied to achieve PaCO2 values of 20, 40, and 60 mm Hg (temperature-corrected). All animals were studied at all three PaCO2 levels in random order. At each level of PaCO2, CBF and masseter blood flow were determined using radiolabeled microspheres. There were no significant differences between groups with respect to mean arterial pressure (approximately 80 mmHg), central venous pressure (approximately 4 mmHg), or hematocrit (approximately 22%). Prior normothermic studies have found delta CBF/delta PaCO2 to be proportional to CBF. Nevertheless, in this study, with hypothermia-induced reductions in CBF, delta CBF/delta PaCO2 was not significantly different between temperature groups. Thus, hypothermia either increased the sensitivity of the cerebral vasculature to carbon dioxide and/or increased the effective level of cerebrospinal fluid respiratory acidosis produced by each increment of temperature-corrected PaCO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928776 TI - Paraben preservatives do not increase intracranial pressure in cats. AB - It has been hypothesized recently that succinylcholine-associated increases in intracranial pressure (ICP) are caused by the paraben preservatives contained in multidose vials. We tested that hypothesis in a standard feline model to determine the effects on ICP of equal-volume injections of preservative-free succinylcholine, succinylcholine with preservatives from multi-dose vials that contain both propylparaben and methylparaben, these preservatives alone at five times the dose contained in the succinylcholine, and normal saline. The preservatives alone increased ICP by 0.08 +/- 0.08 mmHg (+/- standard error; not significant). Normal saline had no effect on ICP. Preservative-free succinylcholine and succinylcholine with preservatives increased ICP by 4.2 +/- 0.10 and 3.8 +/- 0.07 mmHg respectively (P less than 0.01 compared to the preservatives alone and normal saline). The 99% upper confidence limit for the increase in ICP induced by the preservatives alone was 0.42 mmHg. This result suggests that parabens do not cause or substantially augment the ICP increase associated with succinylcholine administration. PMID- 1928777 TI - The effects of insulin infusion on plasma and brain glucose in hyperglycemic diabetic rats. A comparison with placebo-treated diabetic and nondiabetic rats. AB - Experimental and clinical studies have revealed a worsened neurologic outcome after cerebral ischemia in hyperglycemic subjects, including hyperglycemic diabetic subjects. A possible therapy to reduce the magnitude of ischemic brain injury in diabetic subjects would be to use an insulin infusion to reduce brain glucose concentrations to values found in those who are normoglycemic and non diabetic. The present study, using hyperglycemic diabetic rats, examined the effect of an insulin infusion on plasma and brain glucose concentrations to determine their relationship while plasma glucose concentrations decreased. In addition, plasma and brain glucose concentrations were compared to those in diabetic and nondiabetic rats treated with saline. Saline had no effect on the plasma or brain glucose concentrations in the diabetic rats or nondiabetic rats. The saline-treated diabetic rats had increased plasma and brain glucose concentrations as well as an increased brain-to-plasma glucose ratio when compared to the saline-treated nondiabetic rats. When an insulin infusion was used in diabetic rats to decrease plasma glucose to nondiabetic levels over approximately 2 h, the brain glucose concentration decreased. However, the brain to-plasma glucose ratio remained at the "diabetic" value, so that the brain glucose concentration tended to remain increased when compared to normoglycemic, nondiabetic rats. We conclude that if these results are applicable to humans, measurement of plasma glucose in diabetic patients will underestimate the amount of glucose in the brain and this relationship will not be influenced by acute insulin therapy. PMID- 1928778 TI - Contractile responses of guinea pig trachea to oxybarbiturates and thiobarbiturates. AB - To determine what mechanisms are involved in barbiturate-induced tracheal constriction and whether a relationship exists between barbiturate structure and the ability of the barbiturate to induce constriction, we compared the effects of thiamylal, thiopental, methohexital, pentobarbital, and phenobarbital at increasing airway tone in an intact guinea pig tracheal preparation in the presence and absence of cyclooxygenase and thromboxane synthetase inhibition. Whole tracheas were suspended between two cannulas in 50-ml tissue baths and perfused at a constant flow rate with Krebs-Henseleit solution. The contractile responses were assessed by measuring the pressure differential between the tracheal inlet and outlet ports. Barbiturates were added to the bath of each trachea, which was washed between each drug. Each drug was added to produce final bath concentrations of 10(-6), 10(-5), 10(-4), 10(-3), and 3 x 10(-3) M. Tracheas were also pretreated with meclofenamate (10(-6) M) (a cyclooxygenase inhibitor) and UK 37,248 (10(-8) to 10(-5) M) and OKY 046 (10(-9) to 10(-6) M) (thromboxane synthetase inhibitors), and the thiamylal protocol was repeated. All data were normalized to a concentration of carbachol (2 x 10(-6) M) that has been shown to produce maximum constriction in this preparation. Thiamylal and thiopental produced constriction beginning at 10(-4) M and reached a maximum at 10(-3) M (P less than 0.0001). Methohexital, pentobarbital, and phenobarbital did not produce any significant change in airway tone. Pretreatment with meclofenamate (10(-6) M), UK 37,248 (5 x 10(-5) M), and OKY 046 (10(-6) M) prevented thiamylal-induced tracheal constriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928779 TI - Distribution of catheter-injected local anesthetic in a model of the subarachnoid space. AB - Maldistribution of local anesthetic administered through a subarachnoid catheter recently has been implicated as a possible cause of sacral root injury. To examine subarachnoid distribution of catheter-injected local anesthetic, we constructed a model of the subarachnoid space and administered solutions containing lidocaine and methylene blue through sacrally directed catheters. We studied three catheters: a 28-G endport, a 20-G endport, and a 20-G multiple sideport. To determine the injection rates to be used, ten clinicians were observed while they performed mock subarachnoid injections: the mean (+/- standard deviation) "normal" injection times for the 28-G and 20-G catheters were 52.6 +/- 17.2 and 11.9 +/- 7.2 s, respectively. The correlation coefficient for lidocaine concentration estimated by methylene blue spectrophotometric absorbance and measured by immunoassay was 0.977. Administration of hyperbaric local anesthetic through a sacrally directed catheter resulted in restricted distribution of anesthetic with a relatively high peak concentration. Rate of injection was a critical factor affecting distribution; faster injections tended to distribute solution more uniformly and to a higher segmental level, resulting in substantially lower peak concentrations. When catheters were injected at clinically relevant rates, the 28-G catheter produced the greatest degree of maldistribution; this difference appeared to be primarily a function of flow rate. Differences in peak lidocaine concentration between the two 20-G catheters were neither large nor consistent. However, despite sacral placement, the multiple-sideport catheter distributed anesthetic toward "higher" spinal segments more consistently. Distribution was more favorable when the injected solution was less dense (closer to isobaric).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928780 TI - The "educated hand". Can anesthesiologists assess changes in neonatal pulmonary compliance manually? AB - To determine whether anesthesiologists can manually detect significant changes in pulmonary compliance in neonates using an "educated hand," the authors tested whether clinicians could detect clamping of an endotracheal tube connecting a neonatal lung model to one of three anesthesia breathing circuits. The test lungs corresponded to the lung of a full-term neonate (large lung) or a premature neonate (small lung), and the circuits were a disposable Mapleson D and a disposable pediatric circle system with and without a humidifier. Clinicians having four levels of expertise (inexperienced anesthesia residents, experienced anesthesia residents, faculty not specializing in pediatric anesthesia, and specialized pediatric anesthesia faculty) were permitted to choose fresh gas flows, ventilatory pattern, and rate. After an acclimation period, the endotracheal tube connecting the test lung to the circuit was occluded once for 30 s. Clinicians were credited with a successful detection if they reported the occlusion within 15 s and had fewer than one false positive per minute. With the large lung model, only 4 of 24 clinicians detected occlusion with the Mapleson D circuit; similar results were obtained with the other circuits. With the small lung model, the only successful detection occurred with the Mapleson D circuit. Success at detecting occlusion was similarly low for clinicians with different levels of expertise. The authors conclude that the commonly held belief that the "educated hand" permits clinicians to detect subtle changes in pulmonary compliance in neonates during anesthesia (necessitating manual rather than mechanical ventilation) is not true. PMID- 1928781 TI - Malignant hyperthermia during sevoflurane anesthesia in a child with central core disease. PMID- 1928782 TI - Intraoperative use of transesophageal echocardiography with pulsed-wave Doppler evaluation of ventricular filling dynamics during pericardiotomy. PMID- 1928783 TI - Sudden asystole after spinal anesthesia treated with the "pacing thump". PMID- 1928784 TI - Pigtail oximetry. PMID- 1928785 TI - Epidural abscess associated with epidural catheterization. PMID- 1928786 TI - "Do-not-resuscitate" orders during anesthesia and surgery. PMID- 1928787 TI - Pressure-rate quotient in patients undergoing coronary artery bypass graft surgery. PMID- 1928788 TI - Anaphylaxis during anesthesia. PMID- 1928789 TI - Respiratory depression following intrathecal opioids. PMID- 1928790 TI - Another potential complication of a pulmonary artery catheter insertion. PMID- 1928791 TI - More on benzocaine and methemoglobinemia. PMID- 1928792 TI - Site of hemodynamic effects of alpha 2-adrenergic agonists. PMID- 1928793 TI - Failed spinal anesthesia with the Sprotte needle. PMID- 1928794 TI - Pathology of naturally acquired Angiostrongylus vasorum infection in the red fox (Vulpes vulpes). AB - 199 out of 509 foxes culled in a rabies control scheme, were shown to be infected with the metastrongylid parasite Angiostrongylus vasorum. Pathological lesions associated with angiostrongylosis in the fox are described and compared to reported lesions of A. vasorum infection in the dog. The lesions observed in the foxes seemed to be less severe and mainly confined to the ventral parts of the lung lobes which showed granulomatous pneumonia. Right ventricular hypertrophy of the heart was present in all infected foxes. It is believed that the fox population represents an important reservoir of A. vasorum. PMID- 1928795 TI - [Detection of Eimeria tenella antibodies by the serum dye test]. AB - The serum dye test by Sabin-Feldman used in the toxoplasmosis serology was adapted to the Eimeria tenella system. The antibodies detected by this specific test reflect a protective immune response. All animals immunized with virulent and attenuated Eimeria tenella oocyst antigens demonstrated serologically immune reactions. Antigen reactivities over 50% correlate with the grade of protection of animals in challenge test. PMID- 1928796 TI - Diagnosis of canine filariosis: relative sensitivity and specificity of some haematological techniques. AB - Blood samples from 329 dogs of an hyperendemic area in Northern Italy were examined for filariosis. At the filter method (5 microns), taken as reference test, 163 (49.5%) were positive: 160 for Dirofilaria immitis, 2 for D. repens and 1 for both species. The direct smear test (DS), the modified Knott technique (KT) and a further modification of the Knott technique (MKT) were performed in order to assess their relative sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV). The relative SE values are of 88.3%, 91.0% and 91.8% for DS, KT and MKT, respectively. Only the DS relative SP value (99.3%) is less than 100%. Also the PPV and NPV are very high (all above 89%) as well as the values of the coefficient Kappa (all above 0.8), a measure of the concordance between the results of the FT and of the comparison tests. PMID- 1928797 TI - [Chloromyxum sp. (Myxosporidia) in the kidney of Salmo trutta f. fario (Osteichthyes)]. AB - Chloromyxum sp. is described from the kidney of one to four years old brown trout from Thuringia. This species is not distinguishable from C. wardi by light microscopy, but is not identified here with that species because of the different location. PMID- 1928798 TI - Distribution and incidence of ectoparasites on small mammals in a rainforest belt of southern Nigeria. AB - A total of 174 small mammalian hosts were trapped in Ekpoma, Bendel State, Nigeria from October, 1986 to September, 1987 and examined for ectoparasites. 108 infested hosts had 10 species of ectoparasites comprising three species of mites (Laelaps (Echinolaelaps) muricola, Laelaps (E.) gigantea and Laelaps (E.) echidninus); two species of ticks (Amblyomma variegatum and Ixodes sp.); two species of fleas (Xenopsylla cheopis and X. braziliensis); and on especies each of sucking lice (Polyplax spinulosa) and subcutaneous larvae of Cordylobia anthropophaga. Rise in seasonal rainfall positively influenced the incidence of C. anthropophaga and adult fleas, but decrease reduced the incidence of ticks, mites and lice. The incidence of parasitic infestation was influenced by age of host, but not by the sex. Ectoparasite distribution was uneven on their hosts. PMID- 1928799 TI - Goussia carpelli (Apicomplexa, Eimeriorina) from cyprinid fish: field observations and infection experiments. AB - Intestinal tissue samples of 9 cyprinid and gobiid fish species from several hatcheries and ponds in South Bohemia were found to harbour Goussia carpelli-like coccidian oocysts. Furthermore, laboratory transmission of Goussia carpelli, obtained from common carp, was attempted to 9 cyprinid fish species, both laboratory reared and obtained from pond environments. Infection experiments, carried out by fecal contamination (direct transmission) and by using tubificid oligochaetes as paratenic hosts resulted in weak infections in 4 out of 15 Carassius auratus used, but it was not possible to infect any of the other fishes used. PMID- 1928800 TI - Experimental observations on the specificity of Strigea falconispalumbi (Trematoda: Strigeidae) toward planorbid first intermediate hosts. AB - Planorbis planorbis, Planorbarius corneus and Biomphalaria alexandrina (Egyptian strain) were ascertained as new experimental first intermediate hosts, thus bringing the total number of planorbid experimental first intermediate hosts to eight. The highest degree of compatibility was exhibited with P. planorbis (infection prevalence 80%) followed by P. corneus (46.6%), whereas B. alexandrina (as snail species not occurring in the geographical range of S. falconispalumbi) showed the lowest degree of compatibility (23.3%). PMID- 1928801 TI - [Epidemiological findings of Toxoplasma gondii infections of humans in the area of Cottbus]. AB - Using the indirect fluorescence antibody test (IFAT) results concerning the infection of people by Toxoplasma in dependence on age, sex, settlement area and consumption of raw meat in the region of (State Brandenburg) Cottbus are represented as well as on frequency of primoinfections during pregnancy. Infections by Toxoplasma have been found out in 35.6 of 100 cases (n = 3665). With 39.2% women are infected more often than men with 27.1%. Probands of the urbane settlement area show with 37.9% (n = 3402) an higher degree of the infections than probands living in the country with 30.9% (n = 2656). Consumption of raw meat increases the risk of an infection significant. The frequency of primoinfections - found by prospective study with 22559 pregnant women - is placed by 6%, that of connatale infections by 2.6%. PMID- 1928802 TI - Seasonal variation in the occurrence of Pallisentis ophiocephali and Acanthosentis betwai (Acanthocephala) in relation to their fish hosts. AB - Male and female Channa striatus (BL.) and Labeo rohita (HAM.) were examined monthly for Pallisentis ophiocephali (THAPAR, 1930) and Acanthosentis betwai (TRIPATHI, 1959) infections for a period of two years. C. striatus showed greater proportion of infection with P. ophiocephali in March to May and males were significantly more infected than females. L. rohita showed greater infection with A. betwai in June and July and sexes were not differentially affected. The frequencies of male and female P. ophiocephali and A. betwai in the overall sample did not depart significantly from the expected ratio of 1:1 and 2:3 though in certain months the deviation from these ratios was significant. PMID- 1928803 TI - Strigea falconispalumbi (Trematoda: Strigeidae): argentophilic structures of the miracidium. AB - A study of the argentophilic structures of the miracidium of the strigeid digenean Strigea falconispalumbi VIBORG, 1795 was carried out. Miracidia were hatched under laboratory conditions from eggs obtained from adult S. falconispalumbi from the intestine of a naturally infected Buzzard (Buteo buteo). Miracidia were stained with 0.5%. Silver Nitrate solution using standard techniques. The epidermal plates of the miracidium are arranged in four tiers according to the formula (6 + 8 + 4 + 3) = 21. The terabratorium bears 20 papillare. Papillae are also present at the bases of the epidermal plates of the first tier, and also at the margins of the terabratorium between the epidermal plates. The two pores of the excretory ducts are positioned laterally between the third and fourth tiers of epidermal plates. PMID- 1928804 TI - Human gastro-intestinal parasites in Bendel State, Nigeria. AB - Faecal samples from 862 male and female donors of nine age groups (1-90 years) in three geographical zones were screened by the examination of concentrates from formal other concentration technique. The overall percentage incidence of six parasites which were encountered were as follows: Entamoeba coli (19.7%), E. histolytica (3.9%), Giradia lamblia (1.4%), hookworm (29.4%), Ascaris lumbricoides (38.2%) and Trichuris trichiura (7.3%). However, the percentage incidence of parasites in the delta mangrove zone subject to heavy flooding and excess run-offs during the rainy season, were as follows: E. coli (44.7%), E. histolytica (0%), G. lamblia (37.5%), hookworm (44.9%), A. lumbricoides (51.0%) and T. trichiura (77.6%). Except for E. histolytica and G. lamblia, the percentage incidence in the delta zone were comparatively higher than values observed in the better drained middle rainforest and savanna zones. The age groups in the first two decades of life had 61.7% infection and this stabilised to a low level of 2.8% in the eighth and ninth decades. Males and higher protozoan and helminthic infections than females. PMID- 1928805 TI - Two years of infection surveillance in a geriatric long-term care facility. AB - Prospective infection surveillance was carried out for 2 years on two selected units of an 800-bed geriatric long-term care facility. Information was obtained by discussion with attending medical and nursing staff members, chart review, and review of laboratory data. Unit A houses 47 ambulatory Home for the Aged (nursing home) residents (70% female) with a mean age of 89 years. Unit B, for patients requiring chronic hospitalization, houses 32 residents (60% female) with a mean age of 77 years. The infection rates per 1000 patient-days on units A and B were 1.77 and 9.45, respectively. The higher infection rate on unit B was probably due to the presence of a more debilitated patient population. The most common sites of infection on both units were respiratory tract, urinary tract, skin, and soft tissue. The major goals of surveillance in long-term care facilities should be to aid in early detection of outbreaks and to identify preventable endemic infections. Definitions of infection and methods of surveillance that take into account the unique characteristics of elderly subjects residing in long-term care facilities with relatively limited resources need to be developed. PMID- 1928806 TI - Willingness of nursing students and faculty to care for patients with AIDS. AB - Previous research has indicated that nursing students, along with other health care professionals, have expressed an unwillingness to care for patients with AIDS. The purposes of this study were to examine the relationships among nursing students' and faculty members' knowledge of AIDS, attitudes toward patients with AIDS, and willingness to care for them. A descriptive-correlational design was used in which nursing students and faculty (n = 166) at an urban, middle-sized Canadian university completed the AIDS Assess Test developed by Lawrence and Lawrence. Significant relationships were found between willingness to care for and have contact with persons with AIDS and knowledge scores for the group as a whole. Nursing students with more knowledge about AIDS expressed greater willingness to care for AIDS patients. Subjects in the senior year of the nursing program had significantly higher scores on willingness to care for or have contact with persons with AIDS than subjects in other levels of the program and faculty (F(4, 143) = 2.94, p = 0.02). Subjects who knew a homosexual person had significantly higher scores on willingness to care for and have contact with persons with AIDS. PMID- 1928807 TI - APIC guideline for infection prevention and control in the long-term care facility. PMID- 1928808 TI - Effects of nifedipine GITS and atenolol monotherapy on serum lipids, blood pressure, heart rate, and weight in mild to moderate hypertension. AB - Forty-nine patients, with ages ranging from eighteen to seventy years and with mild to moderate primary hypertension (sitting diastolic blood pressure of greater than or equal to 95 mmgH and less than or equal to 115 mmHg) were randomized into a twenty-one-week, double-blind, prospective study to determine the effects of monotherapy of nifedipine GITS (gastrointestinal therapeutic system) versus atenolol on serum lipids, lipid subfractions, apolipoproteins, (apo), and blood pressure (BP). Nifedipine GITS and atenolol significantly reduced blood pressure, but nifedipine GITS reduced sitting and standing systolic BP significantly more than atenolol (p = .001). Sitting and standing heart rate decreased significantly (p = 0.001) during atenolol therapy but did not change significantly during nifedipine GITS therapy. Atenolol increased weight (mean change + 2.2 lb; p = 0.011), but nifedipine GITS decreased weight (mean change - 2.4 lb; p = 0.07). Nifedipine GITS had a more favorable effect on the lipid profile. High density lipoprotein cholesterol (HDL-C) and HDL2 subfractions were increased significantly (p = .001) as were apo A1 (p = 0.037) and apo A2 (p = 0.025). Nifedipine GITS increased HDL3 (NS), reduced triglycerides (TG) (NS), and had no significant effect on total cholesterol (TC) low density lipoprotein cholesterol (LDL-C) and apo B. Atenolol significantly increased serum total cholesterol (p = 0.039) and HDL-C and HDL2 (p = 0.049 and 0.048 respectively). Atenolol increased TG (NS) and apo B (NS) with little change in apo A1 and apo A2. It is concluded that nifedipine GITS had equal or better antihypertensive efficacy than atenolol and had a more favorable effect on the lipid profile. These effects may offer advantages in reducing CHD risk. PMID- 1928809 TI - Effect of L-dopa in young patients with hypertension. AB - The effects of L-dopa on blood pressure, heart rate, plasma renin activity, norepinephrine, epinephrine and prolactin were studied in a randomized single blind trial in 36 patients with essential hypertension. In response to L-dopa, 250 mg administered orally, the blood pressure decreased significantly as compared with the results of placebo treatment. The heart rate and plasma norepinephrine and epinephrine were unchanged. The plasma renin activity and prolactin decreased as a result of L-dopa administration. The administration of a peripheral DA2 dopamine receptor blocker, domperidone (20 mg, orally) prevented the L-dopa-induced reduction in plasma prolactin but failed to block the fall in blood pressure and plasma renin activity. These results suggest that the blood pressure-lowering effect of L-dopa may be mediated through multiple sites involving D1 dopamine receptors, the central nervous system, and the renin angiotensin system. PMID- 1928810 TI - Early exercise test in acute myocardial infarction treated with intravenous streptokinase. AB - The aim of this study was to assess the value of the early exercise test (ET) in patients with acute myocardial infarction (AMI) treated with IV streptokinase (SK). The authors studied 70 patients with first AMI; 31 were treated with SK and 39 were not. Before discharge everyone was given early exercise up to 5-6 METs and catheterized within 22.9 +/- 7.2 days. There was no significant difference in the number of positive ETs between the two groups (11/31 and 14/39 respectively). There was significant difference in favor of: (1) the recanalization of the infarct-related artery in the SK group, (2) the negative ET in patients with recanalized vessels in both groups, (3) the positive ET in patients with multi vessel coronary disease. It is concluded that the results of early ET in patients with AMI are related to the recanalization of the infarct-related artery and the coexistence of multi-vessel coronary artery disease, regardless of SK treatment. Patients with successful thrombolysis have negative ET more frequently. PMID- 1928811 TI - Hemodynamic and hemorheologic effects of i.v. Dilevalol in hypertensive patients. AB - The authors evaluated the effect of Dilevalol infusion on blood pressure, heart rate, central hemodynamics, and rheologic parameters in hospitalized inpatients affected with mild or moderate hypertension. After a dose-finding phase and a washout period of one week, 10 patients aged fifty to seventy-two-years (median 61.5) were given either a single dose of Dilevalol 60 mg or placebo, and seven days later they underwent the other treatment, according to a single-blind, crossover design. Central hemodynamic measurements were performed by means of M mode echocardiography, and hemorheologic parameters were evaluated by means of strain-gauge plethysmography. The maximal increase in lower extremity flow at rest had been obtained with the infusion of 60 mg Dilevalol during dose-finding, and so this dose was chosen for the second part of the study. The infusion of Dilevalol significantly increased rest flow and decreased blood viscosity, but the changes in central, parameters were not considered clinically relevant, although statistically significant. Blood pressure decreased without significant changes in heart rate. Thus, the acute administration of Dilevalol reduced blood pressure, without affecting heart rate and central hemodynamics, confirming the vasodilating effect of the drug. A significant improvement was also shown on blood viscosity in these hypertensive patients. PMID- 1928812 TI - Differentiation of abnormal blood flow patterns in coronary arteries based on Doppler catheter recordings. AB - Abnormal arterial blood flow patterns have been implicated as etiologic factors in thrombosis and atherosclerosis. Intravascular pulsed Doppler ultrasound techniques with fast-Fourier transform analysis offer the opportunity to measure these abnormalities. The authors hypothesized that statistical analysis of radial directed beam spectra could be used to distinguish disturbed from non-disturbed flow and that analysis of conventional axial-directed beam spectra could then be used to distinguish laminar high-shear from laminar low-shear flow. They developed a scaled-up in-vitro model of coronary flow consisting of a glycerol/H2O test fluid flowing through an acrylic cylinder at Reynolds numbers spanning the typical physiologic range within the coronary arteries. A scaled-up Doppler catheter with the capacity for 90 degrees reflection of the beam was placed centrally. Disturbed flow was created by introducing a flow screen, and altered shear rates were produced by changing the Reynolds number. For the radial directed beam studies, the coefficients of variation of the Doppler spectra for the disturbed flow states were significantly greater than for the nondisturbed flow states (p less than 0.01). For the axial-directed beam studies, the coefficients of variation of the Doppler spectra for the laminar high-shear flow states were significantly greater than for the laminar low-shear flow states (p less than 0.01). They conclude that abnormal blood flow patterns can be differentiated by the selective use of radial-directed and axial-directed Doppler catheter recordings. PMID- 1928813 TI - Nuclear magnetic resonance microscopy of atheroma in human coronary arteries. AB - The purpose of this study was to use direct nuclear magnetic resonance (NMR) microscopy to quantitate and image accumulations of atheroma lipids in human coronary arteries and to validate the results by comparison with histologic preparations. NMR microscopy was performed on a superconducting experimental NMR imaging system operating at 2 Tesla with a probe designed for short echo time (TE), strong B1 field strength, and small samples. Data acquisition used multiple offset chemical encoding with offsets based on the thermotropic spectral signature of atheroma lipids within the human arterial vessel wall. Three separate channels of image data yielded color axis display of atheroma within the vessel walls. Atheroma location by histology was identified by rarefaction of stroma, as the lipids are extracted in the process of embedding in paraffin. Perimeters, areas, and a shape index (perimeter2:4 pi area) of lumen, atheroma, and outer wall were determined and compared for NMR vs histology. There was no significant difference in the measurements with the exception of luminal shape indices, which were uniformly larger by histology, attributable to flattening of the vessels during histologic preparation. NMR measurement of atheroma content of coronary artery walls agreed well with histology (r = 0.996). NMR microscopy with color axis display proved able to quantitate and image atheroma in coronary arteries, obviating the distortions and lipid removal associated with fixation, embedding, and sectioning for histology. PMID- 1928814 TI - Effect of variation in heart size on quantitative thallium SPECT. AB - Quantitative single-photon emission tomographic (SPECT) thallium 201 (201Tl) cardiac studies are frequently used to improve test accuracy. One common technique uses polar mapping of relative tracer distribution to compare patient data to emplates from "normal" patient data. Commercial software does not correct for cardiac size variations. This study's purpose was to determine the effect of uncorrected variations in heart size on the variance of the normal population, which is the basis of template significance levels. Twenty-one male volunteers with low probability (less than 5%) for coronary disease underwent SPECT-Tl stress test. Data analysis with and without size correction was performed. Data were corrected for size by use of a three-dimensional compression/expansion algorithm. Quantitative data were generated by radial search to maximum activity in short-axis reconstructions. The mean activity and its variance was calculated from 288 points encompassing the myocardium. Mean and variance differences were analyzed by paired t test. There was no difference in activity means (pT greater than .9), indicating that size correction does not distort the data. The corrected data had, however, significantly lower variance (pT less than .0001). This shows that ventricular size variation contributes significantly to "normal" template variance and may adversely affect diagnostic accuracy in the absence of volume correction. PMID- 1928815 TI - Pentoxifylline in the treatment of distal diabetic neuropathy. AB - Painful diabetic distal sensory neuropathy is a disabling and common complication of diabetes mellitus. There is evidence that microvascular changes resulting in ischemia to the vasa nervorum may contribute to this problem. Pentoxifylline has been shown to improve circulation through partially occluded peripheral vessels and has been postulated to be of potential benefit. Forty adult type II diabetics were enrolled in a double-blind, placebo-controlled study utilizing pentoxifylline for six months. Visual analog scores, nerve conduction studies, and physical examinations were used to evaluate response to treatment. At the end of the six-month trial, there was no significant difference in the patients' pain between the pentoxifylline- and placebo-treated groups. The authors conclude that pentoxifylline is not useful in the treatment of painful distal diabetic neuropathy. PMID- 1928816 TI - Effects of ticlopidine on erythrocyte aggregation in thrombotic disorders. AB - The authors investigated the involvement of red blood cell aggregation in thrombosis by comparing erythrocyte aggregation in patients with myocardial infarction (28 patients) or cerebrovascular accidents (68 patients) with that in a normal control group (38 subjects). The erythrocyte aggregation was assessed by light transmission aggregometer, and aggregation was induced by hexadimethrine bromide. Increased erythrocyte aggregation was detected in all patients with thrombotic disorders. In addition, patients with diabetes mellitus showed a marked increase in erythrocyte aggregation as compared with those without diabetes. The effect of ticlopidine on erythrocyte aggregation was also studied. It was demonstrated that ticlopidine inhibited aggregation in vitro. An inhibitory effect was shown to be dose dependent, with 10 microM ticlopidine inhibiting aggregation completely. After four weeks' oral administration of 200 mg ticlopidine, there was significant decrease of abnormally increased erythrocyte aggregation in patients with thrombosis. PMID- 1928817 TI - A digital splenoportography: more sensitive method of detecting spontaneous splenorenal shunt. AB - Splenoportography was performed upon 195 pediatric patients, including 137 by conventional technique and 58 by digital subtraction technique. The results obtained were compared, and it was found that the percentage of diagnosis of spontaneous splenorenal shunt was higher with digital than with conventional technique. In conclusion digital technique is a more sensitive and safer method than the conventional method. PMID- 1928818 TI - Double aortic arch associated with coarctation of both limbs: a case report. AB - A case of double aortic arch with coarctation of both limbs is described. The patient, a thirteen-year-old girl, demonstrated only the symptoms of coarctation and had no intracardiac anomalies. Discrete coarctation of bilateral limbs distal to the subclavian artery was shown by aortography. Although either double aortic arch or coarctation of the aorta is not so rare, the combination of these two anomalies is quite unusual. This is the third case in the world literature. PMID- 1928819 TI - Coarctation and Marfan syndrome. PMID- 1928820 TI - Quantitation of rotational movements associated with surgical mandibular advancement. AB - Surgical mandibular advancement can be used to correct an anteroposterior and/or vertical malocclusion. The procedure of choice is often the bilateral sagittal split osteotomy (BSSO). By varying the amount of presurgical overbite correction, the rotational movement of the distal segment of the osteotomy can be controlled. Consequently, the malocclusion and the resultant vertical and anteroposterior facial form changes are predictably planned to produce both the desired occlusion as well as the optimal esthetic facial result. Opening rotation of the distal segment elongates the lower face height by varying amounts depending on the nature of the rotation. The amount and type of rotation can be determined and quantified by the technique presented in this paper, which is based on a geometric theorem used to determine the kinematic center of rotation of an object. This technique can shorten treatment time and produce more predictable results. The specific applications are: 1) treatment planning for individual patients, 2) uniform analyses of treatments and grouping of treatment types, and 3) development of more accurate computerized treatment planning programs. PMID- 1928821 TI - Estimation of tongue volume from magnetic resonance imaging. AB - Magnetic resonance imaging was used to estimate the volume of the tongue, oropharynx, and oral cavity in 19 adults. Each subject was imaged and had volume estimations made from the coronal and sagittal orientations. Volume was found by measuring area from a series of images and then multiplying by the thickness of each slice and the gap between each slice in the series. Mean tongue volumes of 71.2cc (coronal) and 79.3cc (sagittal) were found. The estimated volumes were found to be reproducible and each orientation was equally good for defining the anatomy of the tongue and oropharynx. Tongue volumes were found to correlate well with subject body weight, r = 0.86 for the coronal and r = 0.82 for the sagittal orientations. To test the reliability of this technique, tongue volume was estimated for ten New Zealand white rabbits by the same method. The rabbit tongues were then removed and their actual volumes were determined. The estimated tongue volumes from imaging were found to compare closely to the actual volumes but, on average, slightly underestimated actual size. When converted to a percentage, 95% confidence intervals for the estimation of rabbit tongue volume by MRI are -4.3 +/- 25.9% for the coronal and -5.9 +/- 16.5% for the sagittal. PMID- 1928822 TI - The variability of some craniofacial dimensions. AB - The variability of eight linear and five angular dimensions measured on 124 lateral skull radiographs of 10-year-old boys was assessed by means of Bartlett's test for homogeneity of variances and Pitman's test for the comparison of correlated standard deviations. The linear dimensions which demonstrated the greatest variability within the four constituent Angle classes (N = 31) were mandibular body length, total cranial base length, total mandibular length and lower face height. The dimensions which demonstrated the least intra-group but greatest inter-group variability were maxillary length and Angle SNB. The Class II division 2 group exhibited the greatest variation in skeletal morphology; it is therefore postulated that its etiology is mainly dentoalveolar and soft tissue in origin. PMID- 1928823 TI - On the design of looped orthodontic retainer wires. AB - Removable Hawley orthodontic retainers have long been prescribed by clinicians following completion of active therapy. Only minor changes have occurred in the design of the retainer over the past 40 years. Structural, in-service failures of this appliance are typically: 1) permanent (inelastic) deformation of the as prepared labial bow from masticatory action that induces unwanted force transmitted by the appliance to the dentition; or 2) accumulated material damage from removal and replacement of the retainer that eventually results in fracture of the labial bow. This paper reports the results of a series of experimental studies; the overall objective was the optimization of the appliance design, focusing on the labial bow. Wire size, material, temper, canine-loop height, markings for bend placements, heat-treatment of the prepared bow, and two procedures for removing and replacing the appliance were investigated. The collective outcomes suggest a combination of design-parameter values to help maximize the life of the labial bow of the retainer. PMID- 1928824 TI - Mandibular growth and third molar impaction in extraction cases. AB - The position of mandibular third molars was studied in 60 patients from the pedodontic and orthodontic departments at the Federal University of Rio de Janeiro. All individuals received orthodontic treatment with an edgewise appliance following the extraction of first premolars. Examination of superimposed pretreatment and posttreatment cephalometric radiographs led to the observation that mandibular growth is directly related to the positioning of mandibular third molars. Third molar impactions were more likely to occur in cases with a predominance of vertical growth. The larger ascending ramus, the diminution in total length of the mandible and the larger mesial inclination of the crowns also seem to be indicative of third molar impaction. PMID- 1928825 TI - Case report FG. Orthodontic treatment to correct major dental asymmetries. AB - The correction of major dental asymmetries in adults can be challenging. Many adult patients modify their behavior to compensate for skeletal disharmonies, functional shifts and missing teeth. Some skeletal components, including the temporomandibular joint, also adapt in non-growing patients. Extracting premolars will not always correct a marked asymmetry and orthognathic surgical procedures are frequently inappropriate. In the case of Patient FG, extraction of a mandibular central incisor resulted in improved function and esthetics in a relatively short time with minimal expense and trauma. PMID- 1928826 TI - Cloning and sequence analysis of 14 DRB alleles of the bovine major histocompatibility complex by using the polymerase chain reaction. AB - The genetic diversity in the first domain exon of a bovine class II DRB gene was investigated by PCR amplification and DNA sequencing. Genomic DNA samples representing 14 different class II haplotypes, defined by RFLP analysis, were used. The analysis revealed an extensive polymorphism and 14 alleles at a single locus, designated DRB3, were identified. Multiple amino acid substitutions were found in all pairwise comparisons of alleles; 5 to 21 substitutions in the 83 positions compared. The genetic diversity at the amino acid level found in cattle matches the one previously found in the DRB1 locus in man. The significantly higher frequency of replacement substitutions compared with the frequency of silent substitutions provides strong evidence that there is selection for genetic diversity in the bovine DRB3 first domain exon. A comparison of the DRB polymorphism in man and cattle reveals a striking similarity as regards the location of polymorphic positions in the DRB molecule and the degree of polymorphism at polymorphic positions. The majority of polymorphic positions in both species are found in the proposed antigen recognition site of the class II molecule. In addition, there are eight positions which are polymorphic in both species but have not been assigned to the antigen recognition site. The possible functional significance of the polymorphism of these latter positions is discussed. PMID- 1928827 TI - Class II major histocompatibility complex genes of the sheep. AB - The class II genes of the sheep major histocompatibility complex (MHC) have been cloned from two unrelated heterozygous sheep into cosmid vectors. By restriction mapping and hybridization with a number of class II probes of human and mouse origin, the cloned genetic material has been assigned to seven distinct alpha genes, 10 distinct beta genes and 14 beta-related sequences. It was difficult to identify homologues of specific HLA class II genes because of a tendency for the ovine genes to cross-hybridize between HLA probes representing different loci. Such cross-hybridization was especially marked among the beta genes. While DQ and DR homologues have been tentatively identified by several criteria, no genes corresponding to DP have been identified. Cosmids containing class II alpha and beta genes have been transfected into mouse LTK- cells, and surface expression of a sheep class II molecule has been obtained. PMID- 1928828 TI - Expansion of the canine A blood group system. AB - A detailed study of the canine A blood group system was undertaken, resulting in the expansion of this system into a three-factor, four-allelic one with the recognition of an additional subtype, a3. The serological and extensive family data supported the proposed genetic theory of four alleles with dominance with the order being Aa1, Aa2, Aa3 and A-. Gene frequencies of the alleles were determined in various breeds of dogs with frequencies in the general Brisbane population being 0.244 (Aa1), 0.042 (Aa2), 0.045 (Aa3) and 0.669 (A-). PMID- 1928829 TI - Localization of the beta-subunit of follicle stimulating hormone in cattle and sheep by in situ hybridization. AB - The locus for the beta-subunit of the follicle stimulating hormone gene (FSHB) has been determined in both cattle and sheep by in situ hybridization of a bovine and an ovine cDNA probe, respectively, to metaphase chromosomes. Our results show that the FSHB locus is on cattle chromosome 15 in the region of bands q24-qter and in sheep on the cytogenetically homologous chromosome 15, also in the region q24-qter. The mapping of the FSHB gene in cattle together with the location of other genes (CAT, HBB and PTH) previously found to be syntenic in cattle and on human chromosome 11p, defines an evolutionarily conserved synteny. The localization of the FSHB gene to a cytogenetically homologous region in cattle and sheep is consistent with the hypothesis of extensively conserved chromosome structure in these two species. PMID- 1928830 TI - Anti-leucocyte antibodies and embryonic mortality in embryo transferred cows. AB - Cows carrying unrelated transferred embryos (ET) produced anti-leucocyte serum antibodies (aLA) more often than cows carrying their own embryos. Cows carrying the ET showed a higher frequency of cytotoxic reactions against leucocytes from 40-60 randomly chosen cows than individuals carrying their own embryos. The percentage of animals with aLA was higher in cows carrying their second or third transferred embryo than in those with their first transferred embryo. There was no change in the frequency of cytotoxic reactions with repeated pregnancies from transferred embryos. There was no difference in the toxicity of aLA in normal pregnant cows and those carrying transferred embryos. Embryonic mortality (EM) of 35, 73 and 88% was noted during pregnancies from the first, second and third successful ET, respectively. Mortality of 48% occurred in the first pregnancy following an unsuccessful ET. Embryonic mortality of 31% occurred in cows simultaneously carrying their own and a transferred embryo. A direct relationship between the presence of aLA and EM in recipients was not proved. Other fertility problems may lead to EM in cows subjected to repeated transfer of foreign embryos. PMID- 1928832 TI - Use of DNA fingerprints for the detection of major genes for quantitative traits in domestic species. AB - The detection of marker loci linked to major genes or quantitative trait loci (QTL) of large effect in farm animal populations is of great potential value, both because it allows the easy manipulation of the major genes and because it provides a possible route to their ultimate isolation. At present the number of markers available is limited in farm animals. DNA fingerprints provide a promising source of informative marker loci and have the advantage that several loci can be detected on a single Southern hybridization. The disadvantage of DNA fingerprints is the difficulty in determining allelism of DNA fingerprint bands in different pedigrees and the fact that not all potentially resolvable loci can be resolved in a single pedigree. With probes capable of detecting 50 randomly distributed loci, about 50% of the genome of a typical domestic mammal might be expected to be closely linked to a marker (at a distance of 0.2 Morgans or less). If a proportion of DNA fingerprint loci prove to be clustered near chromosomal telomeres or elsewhere in the genome, coverage will be less. In order to detect linkage to a major gene, sires known or suspected to be heterozygous are used to produce large half-sibships, all animals in the pedigree are DNA fingerprinted and the phenotypes of the offspring are recorded. Where several heterozygous sires are available, sires can be selected in an attempt to maximize the number of marker loci resolved. The optimum number of sires needed to produce pedigrees will depend upon the size of the major gene, the number of DNA fingerprint probes available and the characteristics of the DNA fingerprints produced, but often one or two pedigrees will be optimum. Monte Carlo simulation was used to explore the power of detection of linkage between a major gene and a marker locus in a backcross. Maximum likelihood and analysis of variance of mean differences between marker genotypes were of similar power, but maximum likelihood provided reasonable estimates of the major gene effect and its linkage to the marker under some circumstances. One hundred offspring informative for the segregation of a marker would provide reasonable power for the detection of a gene causing a difference between the heterozygote and the homozygote of at least one within sire, within-genotype standard deviation when linkage was very close (0.05 or less).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1928831 TI - New blood group factors Es, Et and a new allele Ebdgjmt (E16) in the pig E blood group system. AB - By immunizing a miniature sow a monovalent reagent (later designated anti-Es) was prepared, detecting an alternative antigen to the Ej. Blood group factors Ej and Es thus form the fifth genetically closed E subsystem. Analyses of selected raw sera containing anti-Ej led to the determination of a further Ej subgroup (designated Et) which is antithetical, mutually excluding with the blood factor Er. New blood factor Et is inherited by alleles Edeghjmnt (= E9) and (= E16). The investigation in pig breeds kept in CSFR indicated that allele Edeghjmnt occurs in Black and White Prestice breed (qE9 = 0.076 +/- 0.010) while allele Edeghjmnr (= E14) only in miniature pigs (qE9 = 0.147 +/- 0.011) and in wild pigs. In an elite herd of Swedish Landrace kept in CSFR a new complex allele Ebdgjmt (= E16) was found. Its frequency in the population studied was 0.058 +/- 0.022. PMID- 1928833 TI - DNA fingerprints of sheep using an M13 probe. AB - The bacteriophage M13 DNA was used to detect hypervariable minisatellites in several families of Booroola sheep as well as Merino and Suffolk sheep. Digestion of sheep DNA gave rise to three to eight fragments with different restriction enzymes demonstrating considerable polymorphism between the different breeds. The length of informative DNA fragments varied in size from 6 to 20kb. The DNA fingerprints generated were individual specific and allowed for differentiation between closely related animals. The pattern obtained with sheep DNA was different from that observed with humans and other vertebrates in the proportion of high molecular weight DNA fragments present. Pedigree analysis of DNA patterns of dams and their offspring for several sets of twins and triplets showed a clear distinction between individuals and failed to reveal the presence of monozygosity. PMID- 1928834 TI - Cosegregation of two allotypes G9 and G16 with the alpha-protease inhibitor variants in pigs. AB - The association between genes encoding for two serum protein antigens (G9 and G16) and alpha-protease inhibitors was analysed in pigs. A recombination frequency between PI and locus controlling G9 and G16 allotypes varied from 0 to 4.8 cM. Data from appropriate matings are consistent with a gene order of PI1 PO1A-PO1B-PI2-(G9, G16). PMID- 1928835 TI - DNA fingerprints of farm animals generated by microsatellite and minisatellite DNA probes. AB - A multi-locus DNA probe, R18.1, derived from a bovine genomic library, detected DNA fingerprints of highly polymorphic loci in hybridization to genomic DNA from poultry and sheep, and of moderate polymorphic loci in cattle and human DNA. The average numbers of detected bands in chickens and sheep were 27.8 and 21.4, and the average band sharing levels were 0.25 and 0.33, respectively. In hybridization to cattle and human DNA, the results were less polymorphic; nevertheless, individual identification is feasible using probe R18.1. The results obtained by R18.1 were compared to results obtained by Jeffreys minisatellite probe 33.6 and two microsatellite oligonucleotides, (GT)12 and (GTG)5. The total number of detected loci using probes R18.1 and 33.6 were estimated in chickens through family analysis of broilers and the maximal number of detectable loci was calculated. PMID- 1928836 TI - Evaluation of the Chem 1 analyzer. AB - The selective multitest Technicon Chem 1 analyser was evaluated according to the guidelines of the 'Comision de Instrumentacion de la Sociedad Espanola de Quimica Clinica', and the protocols of the 'European Committee for Clinical Laboratory Standards' and 'Commission de validation de techniques' of the 'Societe Francaise de Biologie Clinique'. The evaluation was performed in three steps: evaluation in routine conditions, assessment of the interferences and study of practicability. Under routine working conditions, eighteen constituents were studied. Within-run imprecision ranged from 0.6% (CV) for gamma-GT to 4.7% (CV) for AST. Between-run imprecision ranged from 1.6% (CV) for ion sodium to 5.5% (CV) for creatinine. Specimen related carry-over was not within the samples; specimen independent carry-over was found in some of the constituents studied. The relative inaccuracy is good for all the constituents assayed. Haemoglobin (290 mumol.l1) showed a positive interference with urate at three concentration levels (low, medium and high). Bilirubin (up to 300 mumol.l-1) caused a negative interference with creatinine at three concentration levels. Turbidity (trigliceride up to 4 mumol.l 1) stated a positive interference with creatinine at three concentration levels and with AST at two concentration levels (low and medium). Turbidity also caused a negative interference with urate at three concentration levels and with urea at two concentration levels (low and medium). PMID- 1928837 TI - [Update of a selected technique for uric acid determination in plasma and serum. Experimental study and value of derivative spectrophotometry]. AB - A critical study of the candidate reference method for evaluation of uric acid in plasma proposed by the American Association of Clinical Chemistry is followed by testing in six laboratories. The dispersion of results is wide (CV greater than 5%). The importance of turbidity remaining after the deproteinization by trichloracetic acid is clearly demonstrated. This turbidity is really not reproducible from an operation to another one on the same serum. It is very likely responsible of the great dispersion of the results. After that, other deproteinization methods are tried. Ultrafiltration and ultracentrifugation give both defect errors because uric acid is in part bound to proteins. So it is necessary to find another technic which cancels the effects of turbidity on the absorbance readings in the ultra-violet domain. Experimental studies showed that uric acid may be evaluated with a good accuracy by derivative spectrophotometry, in lipid solutions as well as in cloudy ones. Turbidity was created by intralipid suspension additions. Various parameters hitting the method were examined (linearity, smoothing window...), taking as criterion the measure of overloaded serums at different levels. At last, the method is successfully transferred in several sites. In the case of blood serum, the respective influences of derivation and of repetition of final centrifugations are studied in order to estimate the effect of remaining turbidity. By the use of derivative spectrophotometry the improvement of the method of evaluation of uric acid proposed by A.A.C.C. is very noticeable; it reduces the variation coefficient between sites to less than 2%. PMID- 1928838 TI - Automated genetic analysis. AB - Automation of several new, non-traditional techniques for genetic analysis has now become possible. A new system is described that performs gel electrophoretic analysis of DNA including VNTRs, gene segments, and restriction enzyme digests. The instrument detects emitted fluorescence from labeled DNA segments in real time as they electrophore through a gel matrix past a scanning laser beam. Molecular length determination and band quantification is accomplished by comparison to an in-lane standard. Since DNA segments can be labeled and detected with any of four different dyes, the simultaneous analysis of similar length segments from different reactions within a single lane is possible. PCR products are analyzed for research in the areas of human identification and genetic disease. These examples illustrate how automation will play key role in this new era of genetic analysis. PMID- 1928839 TI - The use of peptides to reconstruct conformational determinants; a brief review. AB - In many biological processes, defined regions of proteins are involved in selective recognition. These regions can often be mimicked with peptides and are the main targets for vaccine and drug development. The authors review the use of peptides, to define and ultimately mimic defined protein regions of interest. Especially the role of the Pepscan method is emphasized. This method has been proven to be a useful and fast tool in defining protein regions of interest. It is based on the simultaneously synthesis of multiple peptides coupled to solid supports. Hundreds of peptides can be produced and tested in a relatively short period of time. With the construction of random peptide libraries in recombinant DNA systems, it is now even possible to screen for peptidic determinants without the requirement of preliminary knowledge of primary structure. Having this information, the affinity of peptides can be further enhanced with the Pepscan approach. The power of this approach will be illustrated with results from studies on the development of synthetic vaccines and hormone analogues. PMID- 1928840 TI - Application of engineered chimeric antibodies to the calibration of human antibody standards. AB - Immunoassay quantitation of human antibody depends on the availability of reference sera that have been characterized in terms of their antibody content. This report expands upon the concept of "cross-calibration", using reference (dose-response) curves that have been generated with heterologous antibody as a means of calibrating prospective human antibody standards. Engineered human-mouse chimeric antibody, with a single human isotype and specificity, is used to construct the heterologous dose-response curve from which test antibody response data are interpolated. Transfer experiments are used to define and correct for the percentage of the total chimeric antibody that is immunoreactive and bound to solid phase antigen. The chimeric antibody-based calibration procedure is illustrated using H. influenzae Type B as the model antigen and an engineered chimeric IgG1 antibody that has a known mass per volume content and specificity for the hapten, 4-hydroxy-3-nitro-phenylacetyl (NP). PMID- 1928841 TI - Bacterial vectors to target and/or purify polypeptides: their use in immunological studies. AB - The construction of recombinant proteins by genetic engineering has opened new avenues in basic research (studies on protein organization, protein folding, immunogenicity of proteins, ...) and many different applications. Recombinant proteins which keep properties of both parental proteins are especially interesting. For example, if one protein--the vector protein--is targeted to a given cellular compartment, the other protein--the passenger--may be identically targeted. Also, if the vector protein can be purified by a simple affinity chromatographic procedure, this property may be extended to the passenger. The authors have developed a genetic procedure to detect "permissive" sites within potential vector proteins so that genetic fusion to these sites keep most or all biological properties of the vector. When they used LamB, an outer membrane protein from E. coli, foreign sequences could be expressed at the bacterial cell surface. This may lead to several types of applications: live bacterial vaccines, simple diagnostic tests, selection procedures for peptides with biological activity. When they used the MalE protein, a periplasmic maltose binding protein from E. coli, the passengers could be exported and purified in one-step high affinity chromatography in mild non-denaturing conditions. This led us to a simple preparation and purification scheme for the soluble part of the CD4 receptor for the Human Immunodeficiency Virus (HIV). PMID- 1928842 TI - [Discussion about pretreatment of samples before protein assay with Coomassie brilliant blue]. PMID- 1928843 TI - [Inter-alpha-trypsin inhibitor and its plasma and urine derivatives]. AB - Inter-alpha-trypsin inhibitor (ITI) is a serine protease inhibitor present in human plasma at a concentration of 0.4 to 0.5 g/l. Its molecular weight is about 220 kDa. This glycoprotein is a complex of at least three kinds of subunits: two heavy chains and a light one carrying the antiproteasic activity and corresponding to the urinary trypsin inhibitor (UTI). UTI is a proteoglycan containing a chondroitin sulfate side chain; the stability of the ITI complex is clearly dependent upon the integrity of the glycosaminoglycan part of UTI. ITI is mainly synthetized in liver; in case of inflammatory disorders ITI which is very sensitive to numerous proteases, namely elastase and cathepsin G released by stimulated neutrophils, is degraded into lower molecular weight derivatives present in plasma, among which UTI excreted in urine. The physiological role of ITI still remains elusive; ITI may be considered as a precursor of smaller inhibitors. Owing to their small size, they could secondarily diffuse into the extracellular space and reach tissues to protect them from proteolytic destruction. However, their ability to inhibit human granulocytic elastase seems to be too low for their physiological relevance. UTI was recently shown as exhibiting a growth stimulatory activity for human endothelial cells. In addition, UTI exhibits anti-inflammatory effects, the mechanism of which has not yet been elucidated. Owing to its pharmacological properties, UTI might be of therapeutic value in the treatment of inflammatory disorders. At last, the excretion of UTI, which seems to be depending upon neutrophil activation can be considered as a useful test for detecting and monitoring infections. PMID- 1928844 TI - Modulating secretion of antibodies. AB - Cells have means to ensure that only properly folded and assembled molecules are transported to their final destination, a phenomenon referred to as "quality control" of protein synthesis. Thus, plasma cells secrete only the polymeric form of IgM, retaining and degrading intracellularly assembly intermediates. Due to the failure to polymerize secretory IgM, B lymphocytes do not secrete IgM, while they express the membrane form of IgM on their surface. The selective retention of IgM assembly intermediates is due to disulphide interchange reactions which involve the C terminal cysteine of secretory microseconds chains and unknown protein(s) of the endoplasmic reticulum (ER). Assembly inhibits these reactions, as does addition of reducing agents. In the latter condition, assembly intermediates, otherwise retained and degraded in the ER, are transported to the Golgi, glycosylated and secreted. The developmental control of immunoglobulin secretion is discussed in the more general context of "quality control" of newly synthesized protein within the exocytic compartment. PMID- 1928845 TI - Recombinant bacterial alkaline phosphatase as an immunodiagnostic enzyme. AB - The high turnover number of calf alkaline phosphatase (CAP) is one compelling reason for selecting it as the label in many enzyme immunoassays (EIA's). CAP's usefulness, however, is limited by its inherently low thermal stability which is even further compromised during the chemical preparation of enzyme: antibody conjugates. Bacterial alkaline phosphatase (BAP) could be an attractive alternative to CAP in view of the former's extreme thermotolerance at temperatures as high as 95 degrees C. BAP has not been commonly used in EIA's however, because of its low to moderate catalysis rate. Site-directed mutagenesis was used to overcome BAP's low enzymatic activity and create a protein possessing two desired characteristics: high thermostability and high specific activity. A3 35 fold increased activity over wild-type BAP was obtained in ten different recombinant (r)BAP's via introductions of single-point mutations. The turnover number of the most active mutant, D101S, was shown to be only 1.7-times lower than CAP. This dramatic improvement enables rBAP (D101S) to compete with CAP as a viable alternative label in EIA's. The thermostability of all ten rBAP remained significantly higher than CAP although none were as thermostable as the native BAP. Enzyme:antibody conjugates were prepared with the recombinant enzymes and compared to similarly prepared CAP:antibody conjugates with different Abbott IMx assay protocols and reagents. Excellent correlation between standard curves generated with CAP- and rBAP-containing conjugates were obtained. Furthermore, this correlation was obtained using concentrations of rBAP that were only two times greater than that of CAP. The thermostabilities of the conjugates were also evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928846 TI - Identification of drugs in physiological fluids following on-line liquid chromatographic purification and analysis. AB - This paper describes the application of an automated algorithm for drug identification following the liquid chromatographic on-line separation and purification of drugs in physiological fluids. Two hundred fifty-seven (257) drugs and 45 drug metabolites were assembled for testing. Two internal standards were used which monitored different columns in the multi-step analytical separation. Retention reproducibility over a nine month period was 4 p. cent or less for most drugs. The algorithm for matching unknown peaks against the stored library utilized relative retention, lambda maxima, normalized spectral overlays, wavelength ratios and zero-intercepts from the second derivative in a combined forward-reverse search. Most of the drugs which could not be unambiguously identified were sedatives which eluted in the first minutes of the chromatogram. Diasteromers were partially resolved. Repetitive analysis of 200-400 micrograms/l of amphetamine, diphenhydramine, imipramine and morphine were evaluated to establish an absorption cutoff of 12 mAbs, above which at least 95% of peaks were correctly identified. This corresponded to a signal-to-noise ratio of 12 for the scanning UV detector which was evaluated. PMID- 1928847 TI - Laboratory systems integration: robotics and automation. AB - Robotic technology is going to have a profound impact on the clinical laboratory of the future. Faced with increased pressure to reduce health care spending yet increase services to patients, many laboratories are looking for alternatives to the inflexible or "fixed" automation found in many clinical analyzers. Robots are being examined by many clinical pathologists as an attractive technology which can adapt to the constant changes in laboratory testing. Already, laboratory designs are being altered to accommodate robotics and automated specimen processors. However, the use of robotics and computer intelligence in the clinical laboratory is still in its infancy. Successful examples of robotic automation exist in several laboratories. Investigators have used robots to automate endocrine testing, high performance liquid chromatography, and specimen transportation. Large commercial laboratories are investigating the use of specimen processors which combine the use of fixed automation and robotics. Robotics have also reduced the exposure of medical technologists to specimens infected with viral pathogens. The successful examples of clinical robotics applications were a result of the cooperation of clinical chemists, engineers, and medical technologists. At the University of Virginia we have designed and implemented a robotic critical care laboratory. Initial clinical experience suggests that robotic performance is reliable, however, staff acceptance and utilization requires continuing education. We are also developing a robotic cyclosporine which promises to greatly reduce the labor costs of this analysis. The future will bring lab wide automation that will fully integrate computer artificial intelligence and robotics. Specimens will be transported by mobile robots. Specimen processing, aliquotting, and scheduling will be automated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928848 TI - [Adaptation to the Biomek 1000 workstation (Beckman) of the MHA-TP technique (Ames)]. AB - The microhemagglutination-Treponema pallidum (MHA-TP) was automated with the Biomek 1000 workstation (Beckman). 3,000 serum specimens were studied with manual and automated procedures. Thirty nine serum specimens were found positive by both techniques, neither false positive nor false negative results were observed with the Biomek 1000 workstation. The statistical analyse showed no differences between the two procedures, variations were observed only with low titer sera. In conclusion, time saving and augmentation of productivity obtained by automation of this method could be interesting for a microbiology laboratory. PMID- 1928849 TI - [Evaluation of a radioimmunologic technique for the detection of anti-native DNA antibodies]. AB - The anti-native DNA antibodies were measured by a radioimmunoassay (RIA) type Farr assay in the sera from 648 patients: 108 with active or inactive systemic lupus erythematosus (SLE), 181 with clinical symptoms of another connective tissue disease, 171 with liver diseases, 29 with different pathology and 159 normal sera were obtained from a blood bank. The anti-DNA kit has been calibrated against the first international units/ml. This assay has proved to be sensitive and specific, and appears to be reliable for the diagnosis and follow-up of SLE patients. The authors propose a new reference cut-off level higher than producer's one. PMID- 1928850 TI - [Frequency of martial deficiency in Tunisian women: value and determination of plasma ferritin]. PMID- 1928851 TI - [A growing shortage of anesthesiologists in France. What means should be proposed?]. PMID- 1928852 TI - [Effects of halothane on the electrical activity of respiratory muscles in rats]. AB - This study was designed to investigate the effects of halothane on the electrical activity of the respiratory muscles in rats. Indeed, halothane is known to reduce end-expiratory lung volume, both in man and in animal; this may be due to altered activity in the respiratory muscles. The electrical activity of the diaphragm, parasternal, intercostal and abdominal muscles were recorded using intramuscular electrodes in ten rats weighing between 400 and 450 g each. The rats were prepared under light halothane anaesthesia (tracheostomy, laparotomy, electrode positioning, plaster of Paris cast to impede leg movements). They were placed prone in a 20 1 plexiglass chamber, and allowed to awake. Thereafter halothane was vaporized in this chamber at a known concentration, until the animals no longer reacted to tail pinching. The measurements were carried out during the awake state, and under 2 vol % halothane. Muscle tone was assessed by the thickness of baseline inspiratory muscle activity at the end of expiration (maximally amplified raw electromyographic signals). The measurement of phasic electrical activity was carried out using peak inspiratory integrated electromyographic signals. Under halothane, phasic activity of the diaphragm was slightly reduced (p less than 0.05), whereas tonic activity remained unchanged. Parasternal intercostal muscle activity, both tonic and phasic, was also decreased during halothane anaesthesia (p less than 0.001). No phasic activity occurred in the abdominal muscles, but muscle tone was reduced during halothane administration (p less than 0.01). In rats, the decrease in intercostal muscle tone under halothane anaesthesia could play a major part in the fall in functional residual capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928853 TI - [Value of hormonal treatment with triiodothyronine and cortisone in brain dead patients]. AB - Brain death leads to substantial falls in the plasma levels of cortisol and tri iodothyronine (T3). These alterations may be responsible for physiological instability in these patients, and impairment in donor organ function. A double blind study was therefore designed to assess the possible improvement in metabolism and haemodynamic stability in brain-dead organ donors treated with T3 and cortisone. Forty adult brain-dead patients were randomly assigned to two groups, the patients of the treated group were given every hour, or half hour, 2 or 4 micrograms T3 and 100 mg hydrocortisone intravenously, and those of the placebo group normal saline. Both groups of patients received conventional management for brain-dead donors. The main assessment criterion was the haemodynamic course, appreciated by the Pasys, the CVP and the needs in dobutamine; the secondary criterion was the start, or worsening, of a metabolic acidosis, as judged by the pH, the level of arterial bicarbonate, and the needs in sodium bicarbonate. The two groups were comparable for age, sex, aetiology of brain death, the delay between brain death and the start of the experimental protocol, and the duration of this protocol. There were differences between the two groups, which were not statistically significant: improvement in haemodynamic profile (hormone group 9/20 versus placebo group 10/20); worsening in haemodynamic profile (2/20 vs 4/20); increased requirements in dobutamine (2/20 vs 4/20); decreased requirements in inotropic support (15/20 vs 13/20); mean dose of dobutamine (3.1 +/- 4.2 micrograms.kg-1 vs 2.5 +/- 3.8 micrograms.kg-1); metabolic acidosis (5/20 vs 5/20); mean bicarbonate dose (30.0 +/- 67.7 mmol vs 45.0 +/- 74.2 mmol); donors harvested (20/20 vs 18/20).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928854 TI - [Use of homologous erythrocyte concentrates. Analysis of economical factors]. AB - The factors involved in reducing consumption of bank packed red cells (PRC) were studied over three one year periods (1983, 1987 and 1989) in a Department of Vascular and General Surgery. The effects of autologous blood salvage (started in 1987), associated with the management of homologous blood by a branch of the blood bank inside the operating theater suite were assessed. In 1989, intentional normovolaemic haemodilution became virtually systematic, on top of the intraoperative blood salvage, for all patients due to undergo surgery with a risk of severe blood loss. The number of surgical procedures carried out during those three years did not vary. However, in the same time, the annual consumption of homologous PRC decreased by an overall 56% (36.7% between 1983 and 1987, and 29.8% between 1987 and 1989). This decrease was mostly due to a fall in prescription in the operating theaters, and not in the wards. In the same time, albumin consumption increased sixfold. Such transfusional policies can only be carried out if there is good cooperation between the blood bank and the prescribers of blood products. PMID- 1928855 TI - [Pharmacokinetics of propofol injected after deliberate preoperative hemodilution]. AB - The effects of acute isovolaemic haemodilution (AIH) on propofol pharmacokinetics were studied in 16 male patients scheduled for prostatectomy. They were all ranked ASA 1, and were randomly allocated to two groups, group I (n = 8), who did not undergo any haemodilution, and group II (n = 8), in whom AIH was carried out. Anaesthesia was induced with a single 2.5 mg.kg-1 propofol bolus given in 30 s; maintenance was achieved with fentanyl 2 micrograms.kg-1, atracurium 1 mg.kg-1, and a ventilation with a mixture of nitrous oxide in oxygen 50 %, with enflurane 1 %. Those patients due to be haemodiluted had blood withdrawn before surgery (1,387.5 +/- 423.3 ml), at the same time as they were given the same volume of modified fluid gelatin (Plasmion). The volume of blood to be withdrawn was calculated according to the initial haematocrit, and that required. Haematocrit was decreased to 32.3 +/- 3.9 % (extremes 27 and 37 %). Thereafter blood samples were then collected over a 24 h period, which included surgery. Propofol was assayed in whole blood using high performance liquid chromatography. Analysis with a three-compartment model was carried out. The AIH only altered the central compartment volume (65.5 +/- 15.6 l in the control group vs 83.6 +/- 13.3 l in group II, p less than 0.01). Initial concentrations were not significantly different in the two groups (2,892 +/- 762 ng.ml-1 in controls vs 2,373 +/- 589 ng.ml-1 in the others). Clinically, anaesthesia and recovery were uneventful. It is concluded that the induction dose of propofol in patients scheduled for haemodilution does not require any alteration. PMID- 1928856 TI - [Effect of peroperative analgesia on immediate postoperative oxygen consumption]. AB - Oxygen consumption in the immediate postoperative period was assessed in a series of twelve patients undergoing maxillofacial surgery, randomly assigned to two groups (n = 6 for each). The anaesthetic protocol was the same in all patients: premedication with flunitrazepam 30 micrograms.kg-1, induction with flunitrazepam 20 micrograms.kg-1, fentanyl 5 micrograms.kg-1, thiopentone 5 mg.kg-1, pancuronium bromide 80 micrograms.kg-1, and maintenance during the first three hours with flunitrazepam 10 micrograms.kg-1.h-1 and pancuronium 0.03 micrograms.kg-1.h-1. All the patients were given a continuous infusion of fentanyl during the whole length of the surgery: in Group I (GI), 3 micrograms.kg 1.h-1 and in Group II (GII), 1 microgram.kg-1.h-1. The patients in Group II were also given enflurane 1.2 +/- 0.3 vol %. During the immediate postoperative period, the parameters studied were measured by means of an Engstrom Metabolism Calculator at the 15th, 30th, 45th, 60th, 120th and 240th minutes, and at the time of extubation. In GII, postoperative heart rate and lactic acid levels were higher than in GI (p less than 0.05). Both groups had oxygen consumption values greater than theoretical resting levels. However, postoperative oxygen consumption was greatly increased in GII with respect to GI during the first 4 hours (p less than 0.01). The respiratory quotient was greater in GI than in GII at the end of the study (p less than 0.05). These data indicate that the intraoperative analgesic technique influences postoperative oxygen consumption. A dose of fentanyl of 3 micrograms.kg-1.h-1 is more efficient than one of 1 microgram.kg-1.h-1 associated with enflurane. PMID- 1928857 TI - [Myocardial contusions in closed thoracic injuries: a prospective study]. AB - Various laboratory investigations were assessed with respect to their accuracy in detecting myocardial contusion in patients with blunt chest trauma. All patients, aged between 18 and 50 years, admitted to the intensive care unit for flail chest, sternal fracture, pulmonary contusion, pleural or mediastinal lesion not requiring surgery, were included over a twelve month period. A complete cardiac assessment was carried out, including a physical examination, electrocardiogram, chest X-ray, enzyme assay (ALAT, ASAT, LDH, CPK and MB isoenzyme), two dimensional echocardiography (2D-EC), thallium-201 scintigraphy. Myocardial contusion was diagnosed when an area of decreased or absent thallium-201 uptake was found in the scintigraphy. These latter results were compared with those obtained with the other investigations. Sixteen patients, mean age 34 years, were included; two who died before the end of the investigations were excluded. 2D-EC provided the most useful data (pericardial effusions in a third of the cases). The physical examination, enzyme assays, and chest films were of low value. The investigations carried out six months after the initial trauma showed that long term follow-up was not required. All patients were asymptomatic ten months after their trauma Although the diagnosis of myocardial contusion was made in half the cases using thallium-201 scintigraphy, 2D-EC provided reliable data and had the advantage to be carried out at the patient's bedside. PMID- 1928858 TI - [The anesthesiologist and a Jehovah's Witness patient]. PMID- 1928859 TI - [Increasing shortage of anesthesiologists in France: how many are needed and when?]. PMID- 1928860 TI - [Continuous hemofiltration: an extrarenal filtration method used in intensive care]. AB - Continuous haemofiltration (CHF) mimics physiological glomerular filtration. Blood flows through a haemofilter, which is permeable to water and to all those substances not bound to plasma proteins, of up to about 6,000 d molecular weight. Ten to twenty liters of ultrafiltrate (UF) can be filtered daily. Solute concentration in this UF is very similar to that in plasma water. Because of the large volumes involved, the UF must be replaced continuously with an electrolyte solution. Electrolyte and acid-base disturbances can thus be easily and rapidly corrected. There are different techniques of CHF. Continuous arteriovenous haemofiltration (CAVH) avoids the use of an external blood pump, as the patient's own arterial pressure is used to drive the blood through the filter via a large bore arterial catheter. On the other hand, continuous venovenous haemofiltration (CVVH) requires the use of a blood pump with a pressure alarm and an air bubble detector. Supplementary diffusive transport [CAVH(D),CVVH(D)] can improve the clearance of low molecular weight toxins, such as urea. In these techniques, there is a continuous flow of dialysate in the UF compartment of the haemofilter. One of the major problems with CHF is the anticoagulation of patients who are at risk of developing haemorrhagic complications. Unfractionated heparin is used most often, but other drugs have been used: low molecular weight heparin, prostacyclin, nafamostat, or sodium citrate. The neutralization of heparin has also been suggested. Because the fluid balance can be easily managed by CHF, patients in acute renal failure can be given standard intravenous feeding. Many small endogenous molecules, such as gastrin, are probably removed by CHF. However, most drugs have a molecular weight less than 6,000 d, and are not totally protein-bound. They are therefore likely to be ultrafiltered, and so, become inefficient. As a result, the drugs used should be adapted to the haemofilter, and vice versa. More than any extracorporeal circulation, CHF increases the incidence of bacterial blood contamination, because of its continuous use. Routine blood cultures should be carried out. Moreover, blood is cooled during its passage in the extracorporeal circuit, leading to hypothermia. There are some devices which prevent this. Renal function can be completely replaced with the production of 12 to 15 l UF a day. CHF must be started early on in the course of the renal failure. When the concentration of blood urea is greater than 40 mmol.l-1 diffuse transport must also be used.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1928861 TI - [A radiologic image to be recognized in patients with thoracic injury: the retroligamentary pneumatocele]. AB - A 17-year-old female patient had a road traffic accident. She suffered from a minor head injury, and a right pneumothorax which had to be drained. However, when admitted, an unusual picture was found on the chest film. It was a left para mediastinal shadow with a fluid level, its greater axis being vertical. She underwent a computerised tomographic chest scan. This picture was seen to be in the left costo-vertebral gutter, and in contact with an area of pulmonary contusion in the left posterior basal segment. Another smaller similar picture was discovered on the right side. These were interpreted as being infrapleural pneumatoceles on the mediastinal surface of the lower pulmonary lobes. The patient recovered spontaneously. In fact, these effusions of air and blood can be seen in other areas in the chest (mediastinum, pleura, lung); these are discussed. PMID- 1928862 TI - [Acidoketosis in a chronic alcoholic woman]. AB - A 37-year-old chronic alcoholic female was admitted with epigastric pain, complete anorexia, vomiting and diarrhoea. She was dehydrated, and had polypnoea. Laboratory investigations revealed severe metabolic acidosis (pH 7.14) with a major anion gap (37.4 mmol.l-1), and ketone bodies in blood and urine. Blood glucose concentration was 6.1 mmol.l-1, there was no glycosuria. Rehydration (2 l.day-1 of 5% glucose) together with sodium bicarbonate (500 ml of 1.4% sodium bicarbonate over the first four hours) normalized the pH (7.37). The ketone bodies disappeared on the following day. During the acute illness, were found high blood levels of glucagon and low levels of insulin. The diagnosis of alcoholic ketoacidosis, the pathogenesis of which remains unknown, is discussed. PMID- 1928863 TI - [Accidental epidural injection of hypertonic sodium chloride solution]. AB - Twenty ml of 20% hypertonic saline were accidentally injected into the epidural space of a 53-year-old man with lumbar backache and sciatica. This resulted in severe thoracolumbar pain, which disappeared after he received by the same route 20 ml of 1% lidocaine and 40 ml distilled water. Three months later, the sciatica had almost all disappeared; there remained no motor deficit. A literature survey helped to explain the signs described. Further cases of accidental epidural injections of other drugs are discussed. PMID- 1928864 TI - [Favorable outcome of neoplastic disseminated intravascular coagulation treated with ketoconazole and estrogen derivative]. AB - A prostate biopsy was carried out in a 53-year-old male outpatient with disseminated prostatic carcinoma. Two days later, he was admitted with severe acute anaemia (haemoglobin: 48 g.l-1) and macroscopic haematuria. Biological investigations revealed a disseminated intravascular coagulation (DIC). Symptomatic treatment was undertaken (transfusion of packed red blood cells, platelets, fresh frozen plasma and fibrinogen). However, the patient's condition worsened, and he was admitted to the intensive care unit 48 h later. Despite appropriate symptomatic treatment, the patient's condition continued to worsen. The prostatic origin of this condition was therefore suspected, and anti androgenic treatment was started on day 9 (1,200 mg.day-1 ketoconazole and 2,000 mg.day-1 sodium fosfestrol). Within 48 h, the patient had began to recover in quite a spectacular manner. Ketoconazole starts blocking steroid synthesis within 4 h of giving it. This treatment can be used until oestrogen therapy starts having an effect (about one week). The low levels of testosterone in this case, before starting treatment, suggest that ketoconazole acted on the DIC by a possible cytotoxic effect on the carcinomatous cells. PMID- 1928865 TI - [Verification of bacteriological safety of PCM 40 air conditioner]. AB - This study assessed the bacteriological safety of the bedside air conditioner PCM 40 (Howorth Airtech), used for prevention of intraoperative hypothermia, by blowing filtered warm air through a special mattress. The 3 microns bacterial filter of the device released 2,968 +/- 5,618 particles of diameter less than 3 microns per m3 of room air, containing 78,798 +/- 37,243 of such particles per m3. The amount of bacteries in the air pulsed from the mattress was 30 +/- 41 cfu/m3 vs 120 cfu/m3 in the ambient air and in the hot air supply tubing it reached 6 +/- 5 cfu/m3 vs 175 +/- 77 cfu/m3. It is concluded that bacteriological data do not contra-indicate the use of this air conditioner in the operating theater. The only limitations for use are the position (prone or lateral position) and type of surgery (neurosurgery). PMID- 1928866 TI - [Injectable drugs: resemblances and errors]. PMID- 1928867 TI - [Fatal streptococcus B meningitis at the end of pregnancy]. PMID- 1928868 TI - What are the residual stresses doing in our blood vessels? AB - We show that the residual strain and stress in the blood vessels are not zero, and that the zero-stress state of a blood vessel consists of open-sector segments whose opening angles vary along the longitudinal axis of the vessel. When the homeostatic state of the blood vessel is changed, e.g., by a sudden hypertension, the opening angle will change. The time constant of the opening angle change is a few hours (e.g., in the pulmonary artery) or a few days (e.g., in the aorta). From a kinematic point of view, a change of opening angle is a bending of the blood vessel wall, which is caused by a nonuniformly distributed residual strain. From a mechanics point of view, changes of blood pressure and residual strain cause change of stress in the blood vessel wall. Correlating the stress with the change of residual strain yields a fundamental biological law relating the rate of growth or resorption of tissue with the stress in the tissue. Thus, residual stresses are related to the remodeling of the blood vessel wall. Our blood vessel remodels itself when stress changes. The stress-growth law provides a biomechanical foundation for tissue engineering. PMID- 1928869 TI - Sensation and control of breathing: a dynamic model. AB - A dynamic model of the CO2 respiratory control system is proposed, which can provide a qualitative basis for predicting breathing sensations. The discomfort index, which represents breathing sensations, is assumed to be composed of two sources: the arterial CO2 level and the respiratory motor command. The respiratory controller receives inhibitory neuromechanical and excitatory CO2 signals from the plant. The CO2 signal is enhanced by exercise stimuli. This dynamic multiplicative-type controller is used in simulations of key experiments: exercise and CO2 rebreathing with and without resistive loading. The dynamics of the discomfort index, the respiratory motor command, ventilation, and arterial CO2 concentration conform to the experimental data. The perceptual sensitivity to CO2 relative to respiratory effort is significantly correlated with the slope of hypercapnic ventilatory response. This result shows a clear linkage between ventilatory response and breathing sensations. Although it is shown that the automatic controller effectively minimizes the discomfort index for perturbations about an operating point under certain conditions, the discomfort index itself does not seem to be an underlying control principle of the proposed automatic controller model. Rather, breathing sensations may influence ventilatory responses by modifying the output of the automatic controller. PMID- 1928870 TI - Dynamics of cardiac period responses after prolonged vagal stimulation in the dog. AB - In 12 dogs anesthetised with alpha-chloralose and urethane, and beta-adrenergic blocked with propranolol, the cervical vagi were stimulated for 60 seconds with supramaximal constant current pulses at frequencies between 2.0 and 10 Hz. The time course of the recovery of the cardiac period response, after cessation of vagal stimulation, was analyzed using nonlinear curve fitting techniques. It was found that the recovery phase could be reliably fitted with a function consisting of the sum of up to three exponential terms. The first term has a moderate rate constant of 0.2260 +/- 0.0112 S-1 (SE) and is independent of vagal stimulus frequency and the preceding bradycardia. We propose that this term is associated with a recovery from the bradycardia with a rate constant indicative of the reduction of acetylcholine at the pacemaker caused by hydrolysis and washout. The second term has a small rate constant of 0.0499 +/- 0.0014 s-1 (SE) and a negative gain. This term describes the time course of the post vagal tachycardia observed at cessation of stimulation. It is also independent of stimulus frequency and the preceding bradycardia. The third term has a large and variable rate constant (range: 0.247-8.01 s-1) and becomes increasingly dominant when the preceding bradycardia is large. We propose that this third component arises from a rapid return of the pacemaker focus to the dominant location prior to vagal stimulation. The mathematical characterisation of this component is important to permit the accurate derivation of the time courses of the remaining two components. Curvilinear relationships exist between the gain parameters for each of the exponential terms and the preceding bradycardia. PMID- 1928871 TI - Reconstruction of a human ligamentous lumbar spine using CT images--a three dimensional finite element mesh generation. AB - Detailed investigation on biomechanics of a complex structure such as the human lumbar spine requires the use of advanced computer techniques for both the geometric reconstruction and the stress analysis. In this study, an automated scheme is developed to generate the required three-dimensional finite element grid of a human ligamentous lumbar spine. The computer-based medical images (CT scans) of a cadaveric lumbar spine are used to automatically reconstruct the geometry and the grid of the tissues. The data are then transferred to a mainframe computer in a format suitable for an existing nonlinear finite element code. The process has been designed to allow for a number of user-defined parameters such as the number of elements representing the intervertebral discs and the degree of smoothing of the facet articulating surfaces. This finite element mesh can be used for a detailed stress analysis of the human lumbar spine to understand its mechanical function in both normal and perturbed states. The developed interactive system is also helpful from a diagnostic point of view. PMID- 1928872 TI - Properties of implanted electrodes for functional electrical stimulation. AB - Implanted wire electrodes are increasingly being used for the functional electrical stimulation of muscles in partially paralysed patients, yet many of their basic characteristics are poorly understood. In this study we investigated the selectivity, recruitment characteristics and range of control of several types of electrode in triceps surae and plantaris muscles of anaesthetized cats. We found that nerve cuffs are more efficient and selective (i.e., cause less stimulus spread to surrounding muscles) than intramuscular electrodes. Bipolar intramuscular stimulation was more efficient and selective than monopolar stimulation, but only if the nerve entry point was between the electrodes. Monopolar electrodes are efficient and selective if located close to the nerve entry point, but their performance declines with distance from it. Nonetheless, for a variety of reasons monopolar stimulation provides the best compromise in many current applications. Short duration pulses offer the best efficiency (least charge per pulse to elicit force) but high peak currents, increasing the risk of electrode corrosion and tissue damage. Electrode size has little effect on recruitment and should therefore be maximised because this minimises current density. PMID- 1928873 TI - A theoretical comparison of electric and magnetic stimulation of the brain. AB - We present a theoretical comparison of the electric field produced in the brain by three modalities of transcranial stimulation of the cortex: magnetic stimulation, bifocal electric stimulation, and unifocal electric stimulation. The primary focus of this comparison is the focality and direction of the electric fields produced. A three-sphere model is used to represent the scalp, skull, and brain. All electric fields are calculated numerically. For magnetic stimulation we consider only a figure-of-eight coil. We find that magnetic stimulation produces the most focal field, while unifocal electric produces the least. Fields produced during magnetic stimulation are parallel to the head surface, while fields produced during electric stimulation have components both parallel and perpendicular to the head surface. The electric field produced by magnetic stimulation is shown to be insensitive to the skull conductivity, while that produced by electric stimulation is very sensitive to it. PMID- 1928874 TI - Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol. AB - STUDY OBJECTIVE: To determine the safety and efficacy of a 48-hour IV N acetylcysteine (IV NAC) treatment protocol for acute acetaminophen overdose. DESIGN: Nonrandomized trial open to all eligible patients. SETTING: Multicenter; hospitals included moderate- and high-volume private, university, and municipal hospitals in urban and suburban settings. TYPE OF PARTICIPANTS: Two hundred twenty-three patients were entered. Of these, 179 met inclusion criteria: acute acetaminophen overdose, plasma acetaminophen concentration above the treatment nomogram line, treatment with IV NAC according to the protocol, and sufficient data to determine outcome. INTERVENTIONS: IV NAC treatment consisted of a loading dose of 140 mg/kg followed by 12 doses of 70 mg/kg every four hours. MEASUREMENTS AND MAIN RESULTS: Patients were grouped for analysis according to risk group based on the initial plasma acetaminophen concentration. Hepatotoxicity (aspartate aminotransferase or alanine aminotransferase of more than 1,000 IU/L) developed in 10% (five of 50) of patients at "probable risk" when IV NAC was started within ten hours of acetaminophen ingestion and in 27.1% (23 of 85) when therapy was begun after ten to 24 hours. Among "high-risk" patients first treated 16 to 24 hours after overdose, hepatotoxicity occurred in 57.9% (11 of 19). There were two deaths (two of 179, 1.1%). Adverse reactions resulting from NAC occurred in 32 of 223 cases (14.3%), consisting in 29 of 32 patients (91% of reactions) of transient, patchy, skin erythema or mild urticaria during the loading dose that did not require discontinuation of therapy. CONCLUSION: This 48-hour IV NAC protocol is safe and effective antidotal therapy for acetaminophen overdose. Based on available data, it is equal to 72-hour oral and 20-hour IV treatment protocols when started early and superior to the 20-hour IV regimen when treatment is delayed. Further study will be required to determine its relative efficacy in the high-risk patient treated very late. PMID- 1928875 TI - Simulated acetaminophen overdose: pharmacokinetics and effectiveness of activated charcoal. AB - STUDY OBJECTIVE: To determine the absorption rate of a supratherapeutic dose of acetaminophen elixir and compare the effect of activated charcoal (AC) given at different time intervals on preventing acetaminophen absorption. DESIGN: Randomized, nonblinded, crossover controlled study. SETTING: A certified regional poison control center. PARTICIPANTS: Ten healthy, adult male volunteers from 21 to 39 years old. INTERVENTIONS: Each subject received 5 g acetaminophen (elixir) on four occasions: a control phase plus 30 g of AC administered 15, 30, or 120 minutes after acetaminophen. Serum acetaminophen levels were obtained during the control phase only, and 24-hour urine collections were obtained during all four phases. MEASUREMENTS AND MAIN RESULTS: The highest serum acetaminophen levels were measured 1.4 +/- 0.52 hours after ingestion, and absorption was 97% complete by a mean of 2.05 hours. The administration of AC at 15, 30, and 120 minutes after acetaminophen reduced urinary recovery of acetaminophen and metabolites by 48%, 44%, and 33%, respectively. CONCLUSION: AC significantly reduces urinary recovery but not absorption of acetaminophen when administered two hours after acetaminophen elixir. PMID- 1928876 TI - Transplacental transport of N-acetylcysteine in an ovine model. AB - STUDY OBJECTIVE: Acetaminophen freely crosses the placenta, and acetaminophen ingestion is the most frequent intentional overdose in pregnancy. Although most patients do well after maternal treatment with the antidote N-acetylcysteine (NAC), fetal death with massive hepatic necrosis has occurred. It has never been shown whether NAC crosses the placenta to yield fetal plasma levels equal to those associated with hepatoprotective effects in human beings. Our study objective was to evaluate this in a widely accepted large animal model for maternal-fetal research. DESIGN AND TYPE OF PARTICIPANTS: A nonblinded experiment was performed using four domestic sheep at near-term gestation. INTERVENTIONS: NAC 150 mg/kg IV was administered to the ewe over 15 minutes. After induction of anesthesia, the fetal head was delivered surgically and a neck vein cannulated for blood sampling. Maternal and fetal blood samples were obtained at the end of NAC infusion, at 30- and then at 60-minute intervals for four hours. Plasma NAC levels were determined by gas chromatography/mass spectroscopy (detection limit, 2 micrograms/mL; quantification limit, 5 micrograms/mL). RESULTS: Maternal peak plasma NAC levels were 619, 631, 1,757, and 2,512, micrograms/mL, respectively, within 30 minutes of infusion. However, NAC was only minimally detectable in plasma of two fetal animals and transiently reached quantifiable levels in two others. None of the fetal animals attained serial plasma NAC levels that equalled those associated with therapeutic dosing or hepatoprotective effects in human beings. CONCLUSION: Transplacental transport of NAC is clinically insignificant in a mammalian model resembling the human being. These findings suggest that the human fetal liver is not protected from acetaminophen toxicity by maternal NAC therapy. PMID- 1928877 TI - Digoxin-specific Fab fragments in the treatment of oleander toxicity in a canine model. AB - STUDY OBJECTIVE: To examine the efficacy of digoxin-specific Fab fragments (dsFab) in the treatment of experimentally induced Nerium oleander cardiac glycoside toxicity in a dog model. DESIGN: A nonblined, placebo-controlled experiment. SUBJECTS: Ten adult greyhound dogs of either sex divided into treatment and control groups of five dogs each. INTERVENTIONS: A tincture of oleander was prepared and administered intravenously to each animal. After the onset of cardiotoxicity, the treatment group received 60 mg/kg dsFab IV. MEASUREMENTS AND MAIN RESULTS: All dogs exhibited dysrhythmias meeting our criteria for cardiac glycoside cardiotoxicity within 27 minutes of beginning the infusion. Three of five control dogs had lethal dysrhythmias during the three hour observation period. The remaining two control dogs exhibited dysrhythmias throughout the three-hour experiment. All five of the dsFab-treated dogs survived and converted to normal sinus rhythm within eight minutes of dsFab infusion. Three treatment animals reverted back to nonlethal and hemodynamically stable dysrhythmias after a mean of 107 minutes. CONCLUSION: Large doses of dsFab are efficacious in the treatment of dysrhythmias in this canine model of N oleander cardiac glycoside poisoning. PMID- 1928878 TI - The effect of CPR on plasma diltiazem concentrations in dogs. AB - STUDY OBJECTIVE: To determine the effect of cardiac arrest with CPR on diltiazem concentrations in dogs. DESIGN: Prospective, double-blind, randomized trial. SETTING: Laboratory at a large university-affiliated medical center. TYPE OF PARTICIPANTS: Twenty mongrel dogs. INTERVENTIONS: Following administration of anesthesia, catheters were placed in the pulmonary artery, aortic arch, left ventricle, and right ventricle. Dogs were randomized to receive diltiazem (0.5 mg/kg) either 60 minutes before or during cardiac arrest with CPR. After 13 minutes of cardiac arrest, defibrillation was attempted. MEASUREMENTS AND MAIN RESULTS: Frequent blood samples for diltiazem concentrations were obtained before, during, and after cardiac arrest. The mean diltiazem concentration rose 70% during CPR in the group that received diltiazem before cardiac arrest. The group that received diltiazem during CPR had concentrations five times greater than expected during sinus rhythm. CONCLUSION: Increased diltiazem concentrations are observed during CPR and are probably related to altered distribution encountered during CPR. PMID- 1928879 TI - A randomized, controlled comparison of isoetharine and albuterol in the treatment of acute asthma. AB - STUDY OBJECTIVE: To determine whether treatment of acute asthma with repeated doses of nebulized albuterol leads to greater bronchodilation and lower hospital admission rate than treatment with nebulized isoetharine. DESIGN: Randomized, double-blinded, controlled trial of albuterol and isoetharine. TYPE OF PARTICIPANTS: Patients between 18 and 50 years old presenting with acute asthma. Patients were excluded if they had a history of sensitivity to the study drugs, had congestive heart failure or chronic-obstructive pulmonary disease, or were unable to perform spirometry. One hundred three patients were entered into the study. INTERVENTIONS: All patients received oxygen and methylprednisolone in addition to administration of either isoetharine or albuterol. The nebulized aerosol was given at hourly intervals for a total of three doses. MEASUREMENTS AND MAIN RESULTS: Spirometry was performed before treatment and again at 90 and 180 minutes. Initial forced expiratory volume at one minute (FEV1) was 38.1% of predicted normal for the albuterol group and 36.0% of predicted normal for the isoetharine group. At 180 minutes, FEV1 was 55.6% of predicted normal for the albuterol group and 57.1% of predicted for the isoetharine group (NS). Twenty eight percent of the albuterol group required admission compared with 26% of the isoetharine group (NS). There was no difference in occurrence of side effects between the two groups. CONCLUSION: Repeated doses of albuterol do not lead to a greater improvement in pulmonary function or a lower hospital admission rate than treatment with isoetharine. PMID- 1928880 TI - Verapamil administration to patients with contraindications: is it associated with adverse outcomes? AB - STUDY OBJECTIVES: To determine if the use of verapamil in patients with contraindications is associated with adverse sequelae, thereby assessing whether process measures of the quality of care are correlated with patient outcomes. DESIGN: Retrospective chart review comparing the incidence of adverse outcomes and drug failure in patients with and without contraindications to verapamil administration. SETTING: University hospital emergency department. PARTICIPANTS: All patients more than 12 years old who received IV verapamil during the study period. MEASUREMENTS: The presence or absence of contraindications to verapamil, the occurrence of complications, and the frequency of drug failure were determined by chart review. MAIN RESULTS: Patients with contraindications to verapamil experienced a significantly higher incidence of adverse outcomes and drug failures than those without contraindications. The presence of contraindicated rhythms, low pretreatment blood pressure, and signs of congestive heart failure were each specifically associated with an increased risk of adverse sequelae. CONCLUSION: Verapamil should not be administered to patients with contraindications to its use. In this instance, quality assurance process measures correlate with patient outcomes. PMID- 1928881 TI - Hydrocodone versus codeine in acute musculoskeletal pain. AB - STUDY OBJECTIVES: To evaluate the efficacy and prevalence of side effects of hydrocodone versus codeine in acute pain syndromes. TYPE OF PARTICIPANTS/SETTING: Sixty-two consecutive adult emergency department patients 18 to 70 years old with acute musculoskeletal pain. Patients using other analgesics or having any contraindication to opioid therapy were excluded. In addition, 12 patients were excluded because of insufficient data or study dropout. DESIGN/INTERVENTIONS: In a randomized, double-blind prospective manner, patients received either 5 mg hydrocodone with 500 mg acetaminophen or 30 mg codeine with 500 mg acetaminophen to take on discharge from the ED and every four hours thereafter as needed for pain. MEASUREMENTS: Pain intensity was evaluated by a visual analog scale at zero, one, two, four, eight, 24, and 48 hours. Specific side effects were sought, along with the number of patients reporting inadequate analgesia. MAIN RESULTS: Data were obtained on 50 subjects (25 per group). Mean and median pain scores did not differ significantly at time zero (x vs y, 6.03 vs 5.99 and 6.8 vs 6.1, respectively) or subsequent intervals. Side effects were noted in eight hydrocodone/acetaminophen and 18 codeine/acetaminophen patients (P = .005). No significant differences in gastrointestinal side effects were reported; however, less nausea or vomiting was reported in the hydrocodone group (P = .23). Central nervous system side effects (sedation or lightheadedness) were reported in six hydrocodone/acetaminophen patients compared with 16 codeine/acetaminophen patients (P less than .005). In addition, no hydrocodone/acetaminophen patients reported inadequate analgesia compared with six codeine/acetaminophen patients (P less than .05). CONCLUSION: Although pain scores were not significantly different, hydrocodone may be a more effective analgesic than codeine in acute musculoskeletal pain, as demonstrated by significantly fewer treatment failures. Central nervous system side effects are less common with hydrocodone than with codeine. PMID- 1928882 TI - Effects of calcium channel blocker overdose-induced toxicity in the conscious dog. AB - STUDY OBJECTIVE: To evaluate the effects of nifedipine, diltiazem, and verapamil overdose on systemic hemodynamics and blood flows to the coronary, superior mesenteric, renal, and iliac arteries in the unanesthetized dog. DESIGN: Nonblinded, controlled animal study. SETTING: Research laboratory of a large pharmaceutical company. TYPE OF PARTICIPANTS: Nineteen healthy mongrel dogs obtained from a commercial supplier. INTERVENTIONS: Under general anesthesia, flow probes were placed about the ascending aorta, circumflex coronary, superior mesenteric, renal, and iliac arteries; a micromanometer was implanted into the tip of the left ventricle; and a catheter was inserted into the descending aorta. Experiments were performed after a recovery period of at least two weeks. MEASUREMENTS AND MAIN RESULTS: Arterial blood pressure, heart rate, cardiac output, left ventricular pressure, and regional blood flows were measured prior to drug administration, and after 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg IV administration of the study drugs. Dogs receiving diltiazem or verapamil also received a dose of 10.0 mg/kg. When the blood pressure had been reduced from baseline by 30%, 1.43 mg/kg nifedipine IV (six dogs) decreased total peripheral resistance by 51%, increased cardiac output by 35%, and increased heart rate by 132%. Coronary blood flow and iliac blood flow increased 93% and 45%, respectively, but mesenteric blood flow and renal blood flow were not significantly altered. Diltiazem (eight) and verapamil (seven) at equivasodepressor doses (1.43 to 4.43 mg/kg) caused less peripheral vasodilation and reflex tachycardia. At severely toxic levels when arterial blood pressure fell by 50%, all three drugs decreased cardiac output. Nifedipine still increased heart rate. Diltiazem and verapamil caused high-grade atrioventricular block, resulting in bradycardia. All three drugs caused a redistribution of cardiac output favoring the coronary bed over the other beds. CONCLUSIONS: In the conscious dog, calcium channel blocker-induced hypotension at the moderate level is associated with disparate effects on systemic hemodynamics, probably resulting from differential reflex sympathetic activation. However, at a more severe level, their toxic effects are similar and manifested predominantly by their actions on the slow calcium channel. PMID- 1928883 TI - Treatment of acute mountain sickness: hyperbaric versus oxygen therapy. AB - STUDY OBJECTIVES: To compare the benefits of simulated descent in a hyperbaric chamber with those of supplementary oxygen for the treatment of acute mountain sickness. DESIGN: A prospective study. SETTING: The Snake River Health Clinic in Keystone, Colorado, which has an altitude of 2,850 m (9,300 ft). TYPE OF PARTICIPANTS: Twenty-four patients who presented with acute mountain sickness. INTERVENTIONS: A simulated descent of 1,432 m (4,600 ft) was attained by placing the patients in a fabric hyperbaric chamber and pressurizing the chamber to 120 mm Hg (2.3 PSI) above ambient pressure. Patients were randomly assigned to either the hyperbaric treatment or treatment with 4 L of oxygen given by facemask; both treatments lasted for two hours. MEASUREMENTS AND MAIN RESULTS: Mean arterial oxygen saturation (SaO2) increased 7% (84 +/- 2% to 91 +/- 1%) with pressurization and 14% (83 +/- 4% to 96 +/- 1%) with oxygen during treatment over pretreatment levels. Symptoms of acute mountain sickness decreased as rapidly with pressurization as with oxygen treatment, despite significantly higher SaO2 in the oxygen-treated group during treatment. Symptomatic improvement was retained in both groups at least one hour after treatment. CONCLUSION: Simulated descent in a fabric hyperbaric chamber is as effective as oxygen therapy for the immediate relief of acute mountain sickness. PMID- 1928884 TI - Emergency department return visits in chronic obstructive pulmonary disease: the importance of psychosocial factors. AB - STUDY OBJECTIVES: Relapses are common after treatment of decompensated chronic obstructive pulmonary disease (COPD) in the emergency department. The purpose of this study was to identify psychosocial and pulmonary function variables that distinguish patients who relapse from those who do not. DESIGN: Retrospective case analysis. A relapse was defined as an unscheduled return to the ED within two weeks of treatment. SETTING: 475-bed Veterans Administration Medical Center. TYPE OF PARTICIPANTS: 33 male veterans with COPD who used the ED. MEASUREMENTS: Demographic profile, a Likert-scaled questionnaire about illness beliefs, and physiologic data obtained by chart review. MAIN RESULTS: Patients who relapsed at least once (R patients) were more likely to be widowed, separated, or divorced than patients who did not relapse at any time (N patients) (52.4% vs 8.3%; P = .011). R patients were more likely to have lost a first-order relative within three years (57.1% vs 8.3% P = .006). Stepwise logistic regression showed that the loss of a first-order relative, a negative attitude about prognosis, and a higher forced vital capacity distinguished R from N patients. Stepwise linear regression showed that six specific illness beliefs, distance of the home from the hospital, and baseline bronchodilator response correlated with the number of relapses (multiple r2 = 0.82; P less than .001). CONCLUSION: Social and psychological parameters are closely correlated with relapse in patients with decompensated COPD. PMID- 1928885 TI - Oral transmucosal fentanyl citrate for analgesia and sedation in the emergency department. AB - STUDY OBJECTIVE: To evaluate the safety and efficacy of oral transmucosal fentanyl citrate (OTFC) as a noninvasive method of providing analgesia and sedation for patients in the emergency department. DESIGN: Prospective, nonblinded. SETTING: ED of a tertiary care university hospital. TYPE OF PARTICIPANTS: Ten patients, 6 to 34 years old, with acute painful conditions requiring treatment in the ED. INTERVENTIONS: Premedication with OTFC and local anesthetic prior to incision or wound closure. MEASUREMENTS AND MAIN RESULTS: Pain and activity (sedation) scores, vital signs (including systolic and diastolic arterial blood pressures, heart and respiratory rates, and pulse oximetry-determined oxygen saturation) were measured before and at two- to ten minute intervals during and after OTFC consumption. All patients accepted OTFC. Patients received an average of 13.7 +/- 2.5 micrograms/kg of fentanyl citrate in 11.8 +/- 6.8 minutes. Decreases in pain were reported in two patients in two minutes and by all patients 14 minutes after beginning OTFC consumption. Sixty percent of patients became drowsy or sedated 12 to 30 minutes after beginning OTFC. Vital signs and oxygen saturation changes were small and not clinically significant. The most important side effects were pruritus (30%), nausea (20%), and dizziness and dry mouth (40%). All were considered mild and not disturbing, although one patient required post-procedure antiemetic therapy for recurrent vomiting. The mean time to discharge from the ED was 139 +/- 54 minutes after receiving OTFC. CONCLUSION: OTFC may be useful in providing rapid, noninvasive analgesia and sedation in the ED and deserves further evaluation. PMID- 1928886 TI - Bone marrow aspirate as an accessible and reliable source for critical laboratory studies. AB - STUDY OBJECTIVE: To determine whether laboratory studies performed on bone marrow aspirate can be used to predict values in the peripheral blood of human beings. DESIGN: Prospective correlative study. SETTING: Tertiary care pediatric hospital. TYPE OF PARTICIPANTS: Fifteen patients from the hematology-oncology division of Children's Hospital, Oakland, California, were studied during routine diagnostic bone marrow aspirations. INTERVENTIONS: Aliquots of serum and bone marrow obtained as part of routine diagnostic studies were analyzed. MEASUREMENTS AND MAIN RESULTS: Venous and bone marrow samples were analyzed for blood gas values, hemoglobin, and serum chemistries. Bone marrow specimens were found to reliably predict venous values of pH, bicarbonate, base excess, PCO2, hematocrit, sodium, chloride, and glucose. Bone marrow was not predictive of blood oxygenation, potassium, or ionized calcium. CONCLUSION: This study demonstrates in human beings what has previously been shown in animals--that the bone marrow is an alternative source of blood for a variety of laboratory studies. PMID- 1928887 TI - Naloxone reversal of hypotension due to captopril overdose. AB - The hemodynamic effects of captopril and other angiotensin-converting enzyme inhibitors may be mediated by the endogenous opioid system. The opioid antagonist naloxone has been shown to block or reverse the hypotensive actions of captopril. We report a case of an intentional captopril overdose, manifested by marked hypotension, that resolved promptly with the administration of naloxone. To our knowledge, this is the first reported case of captopril-induced hypotension treated with naloxone. Our experience demonstrates a possible role of naloxone in the reversal of hypotension resulting from captopril. PMID- 1928888 TI - Ethanol sensitivity. AB - Ethanol sensitivity is a syndrome of flushing, tachycardia, weakness, fatigue, and other dysphoric symptoms in response to relatively small doses of ethanol. We describe a case of extreme ethanol sensitivity presenting with coma and review the pathophysiology of the syndrome. PMID- 1928889 TI - Theophylline toxicity secondary to ciprofloxacin administration. AB - We report the case of a 79-year-old woman who presented from a skilled nursing facility to the emergency department with signs and symptoms of theophylline toxicity and a serum theophylline concentration of 53.7 mg/L. The patient had been on a regular regimen of aminophylline for two months, with the addition of ciprofloxacin three days before arrival as the only identifiable potential cause of theophylline intoxication. She was monitored and treated conservatively with serial doses of activated charcoal, which resulted in a reduction of her serum theophylline level to a therapeutic concentration in 15 hours without adverse sequelae. The number of cases of theophylline intoxication secondary to concurrent ciprofloxacin administration is likely to increase, especially in nursing home populations, and it should be suspected when these patients present to the ED with the appropriate signs and symptoms. Management of theophylline intoxication should be based on clinical presentation as well as concentrations of the drug. PMID- 1928890 TI - Acute barium poisoning with respiratory failure and rhabdomyolysis. AB - Barium is a divalent alkaline earth metal used as the insoluble sulfate salt in contrast radiography and soluble acid salts in industry. Barium poisoning results from ingestion or inhalation of the acid salts; the most common poisoning occurs after ingestion of the rodenticide barium carbonate (BaCO3). We report seven cases of BaCO3 poisoning in one family; three hospitalized patients displayed classic signs of barium toxicity, and one patient also developed rhabdomyolysis, respiratory failure, and hypophosphatemia. All patients survived. Rhabdomyolysis has not been previously reported in barium poisoning, and this is the first reported barium poisoning epidemic in the United States. The history, pathophysiology, and treatment of barium poisoning are reviewed. PMID- 1928891 TI - Acute theophylline intoxication. AB - We describe a case of intentional acute theophylline intoxication with cardiac, cerebral, and gastrointestinal features of moderate-to-severe toxicity. The unusual metabolic and hematologic sequelae included hypokalemia, hyperglycemia, metabolic acidosis, extreme neutrophilia, increased creatinine levels attributed to muscle damage, and hematuria. The implications of these unusual findings for the management of acute theophylline intoxication include the recognition that these effects can be due to intoxication per se and do not necessarily indicate a primary endocrine disorder or infection. PMID- 1928892 TI - The ten commandments of emergency medicine. PMID- 1928893 TI - Managing Jehovah's Witnesses: medical, legal, and ethical challenges. PMID- 1928894 TI - Patients' rights and the role of the emergency physician in the management of Jehovah's Witnesses. PMID- 1928895 TI - American College of Emergency Physicians Ethics Manual. AB - Ethical concerns are a major part of the clinical practice of emergency medicine. The emergency physician must make hard choices, not only with regard to the scientific/technical aspects but also with regard to the moral aspects of caring for emergency patients. By the nature of the specialty, emergency physicians face ethical dilemmas often requiring prompt decisions with limited information. This manual identifies important moral principles and values in emergency medicine. The underlying assumption is that a knowledge of moral principles and ethical values helps the emergency physician make responsible moral choices. Neither the scientific nor the moral aspects of clinical decision making can be reduced to simple formulas. Nevertheless, decisions must be made. Emergency physicians should, therefore, be cognizant of the ethical principles that are important for emergency medicine, understand the process of ethical reasoning, and be capable of making rational moral decisions based on a stable framework of values. PMID- 1928896 TI - In re patient transfer. PMID- 1928897 TI - The road to academic respectability. PMID- 1928898 TI - Wenckebach-type atrioventricular block in severe alcohol intoxication. PMID- 1928899 TI - Serologic enzyme-linked immunosorbent assay responses of calves vaccinated with a killed Mycobacterium paratuberculosis vaccine. AB - The purpose of this study was to document the effect of calfhood vaccination for Mycobacterium paratuberculosis on a serologic ELISA. Fifteen calves vaccinated with a killed paratuberculosis vaccine and 5 unvaccinated control calves were tested from the first through the fifteenth month of life. Age of vaccination ranged from 5 to 40 days. Blood samples were collected prior to vaccination and periodically thereafter. Serum antibody was analyzed by use of the ELISA. All calves were ELISA-negative prior to vaccination. Thirteen of 15 vaccinated calves became ELISA-positive between 2 and 6 months after vaccination. The unvaccinated cohort remained ELISA-negative. Wide-spread use of vaccine may interfere with diagnosis of paratuberculosis and with control programs that are based on serologic tests that measure humoral antibody. PMID- 1928900 TI - Flow cytometric study of oxidative burst activity in bovine neutrophils. AB - A flow cytometric procedure was evaluated to measure the oxidative burst activity (hydrogen peroxide formation) of bovine neutrophils. The method involves measuring the oxidation of intracellular dichlorofluorescein to fluorescent dichlorofluorescein (DCF). Phorbol myristate acetate (PMA) was used to perturb the neutrophil plasma membrane. The sources of variation introduced into the DCF assay were also examined. The sources of variation were attributable to the isolation of neutrophils from blood, variation between duplicate assays and duplicate flow cytometric determinations of oxidative product formation, variation in neutrophil oxidative product formation among cows, and the variation (over repeated daily and weekly neutrophil isolations) in neutrophil oxidative product formation. A final objective was to determine effects of dexamethasone on oxidative product formation, and whether differences existed between blood and mammary neutrophils in oxidative product formation. There was an increasing trend in the formation of DCF with increasing time of incubation and with increasing PMA concentration. Increasing the concentration of PMA decreased lag time and increased the rate of oxidative product formation. The increase in DCF formation was statistically significant up to a PMA concentration of 10 ng/ml. This concentration was considered optimal for bovine neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928901 TI - Plasminogen activator production by bovine milk macrophages and blood monocytes. AB - The type of plasminogen activator (PA) produced by bovine milk macrophages has been determined. Macrophages produce a PA protein with molecular weight of 28,000 and isoelectric point of 8.5, and with enzymatic activity independent of fibrin. These characteristics are identical to those reported for bovine urokinase-PA. Although blood monocytes and milk macrophages produce PA after stimulation with lipopolysaccharide, mammary macrophages are clearly limited in their ability to release PA. At maximal stimulation, 78% of the PA produced by milk macrophages remained cell-associated. In marked contrast, blood monocytes released 76% of the PA produced into the culture medium. Macrophages isolated from mastitic quarters produced higher (2.5 times) amounts of PA, compared with those produced by macrophages isolated from healthy quarters. However, in both cases, macrophages were unable to secrete the protein already produced. The limited PA secretion by milk macrophages might be a residual function of a differentiated macrophage population. PMID- 1928902 TI - Comparison of four immune variables and pulmonary lesions of goats with intrapulmonary exposure and subsequent intrathoracic challenge exposure with Pasteurella haemolytica. AB - A comparison of immune variables following lung sensitization with live Pasteurella haemolytica serotype 1 (Ph1)-impregnated agar beads was done in 2 separate trials. The Ph1 immune variables studied were blood bactericidal activity, serum bacteriolysis, total classical complement, and indirect hemagglutination antibody. Each trial had 16 male weanling goats: 6 controls and 10 principals. In trial 1, each goat was surgically catheterized through the trachea, then the material was deposited in a bronchus. The controls received only agar beads and the principals received agar beads impregnated with live Ph1. These goats were studied for 32 days, euthanatized, and necropsied. In trial 2, the controls were each transthoracically injected with agar beads into the left lung and the principals were similarly injected with agar beads impregnated with live Ph1. These goats were studied for 35 days, then challenge exposed transthoracically by injection of Ph1 in saline solution (1.2 x 10(7) CFU/ml) into the right lung. Four days later, they were euthanatized and necropsied. The volume of lung consolidated tissue was an excellent measure of Ph1 immunity. Principal goats generated solid protective immunity to subsequent challenge exposure because minimal or no lung consolidation was observed, whereas large volumes of lung consolidation were seen in the controls. The principal goats in trial 1 gave a weak serum indirect hemagglutination Ph1 antibody response, which was attributed to the bronchial method of depositing the Ph1. The corresponding response of the control group remained negative. The Ph1 agar beads (1 x 10(6) CFU in 0.5 ml) protected the bacteria from immediate phagocytosis and lysis as indicated by the induced pneumonic deaths of 2 principals 5 days later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928903 TI - Use of adult dog serum as a substitute for colostrum in the neonatal dog. AB - Failure to obtain passive transfer of immunity via colostrum can be detrimental to the health and survival of a young pup. It has been stated that pups that do not receive colostrum in the first 2 days after birth, be given adult dog serum as a source of protective immunoglobulins. Twenty-five Beagle pups were obtained by cesarean section from 6 Beagle bitches. The pups were allotted to 3 groups at birth. Group 1 was a control group and was allowed to suckle colostrum. Group-2 pups received 22 ml of pooled adult dog serum/kg of body weight (10 ml/lb) SC at birth. Group-3 pups were given 22 ml of pooled adult dog serum/kg by stomach tube at birth. Pups from groups 2 and 3 were separated from the bitch for 48 hours to prevent colostral antibody absorption and were fed a commercially available milk replacer by stomach tube. After 48 hours, all pups were returned to the bitch until they were weaned at 6 weeks of age. Blood samples were collected from all of the pups at birth and on days 1, 2, 7, 14, 21, 28, and 35. The concentration of IgA, IgG, and IgM in serum was determined by radial immunodiffusion and compared by use of a one-way analysis of variance. The control pups had significantly higher serum concentrations of IgA and IgG, than the pups in groups 2 and 3 on days 1 and 2 and 2 and 7, respectively. Group-2 pups had significantly higher serum IgM concentrations on day 1 than either group 1- or group-3 pups. PMID- 1928904 TI - Antigenic analysis of four species of the genus Ehrlichia by use of protein immunoblot. AB - The antigenic profile of Ehrlichia canis, E risticii, E sennetsu, and E equi was investigated by the use of protein (western) immunoblot technique. Results of analysis of serum from acutely and chronically infected animals indicated that the 4 Ehrlichia species share a unique 25-kD polypeptide in addition to other peptides. Immune sera from dogs inoculated with E canis recognized a wide range of E canis polypeptide antigens, as determined by western blot analysis. A larger number of E sennetsu polypeptides were detected when homologous antiserum and antiserum to E equi were used. The latter antiserum did not recognize antigens of E canis or E risticii. Antisera to E canis, E risticii, and E sennetsu detected E equi antigens. Data indicate that a 25-kD protein is a common antigen among the species of the genus Ehrlichia and that the ascending order of abundance of immunodominant determinants in the 4 species of Ehrlichia studied would be: E risticii----E equi----E sennetsu----E canis. Implications of these findings for diagnosis of ehrlichial infections and prophylaxis are evident. PMID- 1928905 TI - Actinobacillus suis-like organisms and evidence of hemolytic strains of Actinobacillus lignieresii in horses. AB - Thirty-seven local isolates of Actinobacillus suis-like organisms from diseased and clinically normal horses and 1 llama were compared with reference strains of A suis, A lignieresii, A equuli, A capsulatus, A hominis, A (Pasteurella) ureae, and equine A suis-like organisms (ASLO) previously described in literature. Comparison was by cultural characteristics, carbohydrate fermentation, enzyme profiles, and whole-cell protein polyacrylamide gel electrophoresis. Carbohydrate fermentation, determined by API-CH gallery, divided 36 equine ASLO isolates into 6 API-CH biotypes. The llama isolate was an additional distinct biotype. The biochemical comparisons between A suis and ASLO did not reveal remarkable and consistent differences. Enzyme analysis revealed 5 API-ZYM biotypes, one of which included the same strains as one of the API-CH biotypes and consisted in both instances of 4 esculin-negative ASLO cultures and the reference strain of A lignieresii. We conclude that the 4 strains were hemolytic variants of A lignieresii. Protein electrophoresis disclosed 15 banding patterns, 10 of which represented equine ASLO strains. The reference strains of A suis shared the pattern predominant among equine ASLO. Four of the remaining reference strains of Actinobacillus species each had a unique profile, whereas the type strain of A capsulatus and the llama isolate had similar profiles. The groupings of cultures resulting from the different testing methods had little relation to each other and to the anatomic source of the strains except the strains comprising API-CH biotype II, which originated in the equine respiratory tract, and the A lignieressi cluster. PMID- 1928906 TI - Transformation of Corynebacterium pseudotuberculosis by electroporation. AB - Corynebacterium pseudotuberculosis was transformed by electroporation, using pNG2, an erythromycin-resistance plasmid from C diphtheriae. Corynebacterium pseudotuberculosis cultivated in brain-heart infusion broth was washed 3 times with water, and resuspended to a final concentration of about 5 x 10(13) colony forming units/ml. An electroporator constructed in our laboratory incorporated an electrode with 0.8-mm interelectrode gap, using disposable spectrophotometer cuvettes as containers for electroporation. The pNG2 was prepared in Escherichia coli and 4 to 16 micrograms of pNG2 DNA was mixed with 400-microliters amounts of cell suspension in prechilled cuvettes. After incubation on ice for 5 to 10 minutes, the mixture was electroporated at field strengths of up to 18 kV/cm, mixed with 1.5 ml of brain-heart infusion broth, and incubated at 37 C for 2 hours with agitation. Aliquots were then plated on brain-heart infusion blood agar with 15 micrograms of erythromycin/ml. Corynebacterium pseudotuberculosis was transformed at a maximal efficiency of approximately 4 x 10(4) transformants/micrograms of pNG2 DNA. Most total transformants and most transformants per microgram of pNG2 were generated at a field strength of 18 kV/cm. When the concentration of pNG2 DNA was varied, the average total number of transformants increased through a concentration of 30 micrograms/ml, but the efficiency of transformation was highest at the lowest DNA concentration. Transformants contained unmodified pNG2. PMID- 1928907 TI - Effects of bacterial infection and castration on prostatic tissue zinc concentration in dogs. AB - An Escherichia coli bacterial prostatitis was experimentally induced to determine the effect of bacterial infection on prostatic tissue zinc concentrations in castrated and gonadally intact male dogs. Five of the 22 mixed-breed dogs (group 1) had no culture evidence of infection 2 weeks after the instillation of bacteria into the prostate gland. The remaining 17 infected dogs were allotted to 2 groups; 1 group of dogs was subjected to castration (group CA, 7 dogs), and the other group of dogs was subjected to sham operation (group SO, 10 days). The groups were divided into groups of dogs with prostatic infection at necropsy (groups CA-I and SO-I), and those dogs without prostatic infection at necropsy (groups CA-N and SO-N). Urine, prostatic fluid, and prostatic tissue (week 0, 7, +/- 12) specimens were obtained for bacteriologic culturing to determine whether prostatic infection was present. Prostatic tissue was obtained at necropsy (week less than 6, 7, or 12) for analysis of zinc concentration by atomic absorption spectrophotometry. The logarithmic mean prostatic tissue zinc concentrations were compared between groups. Group CA had a significantly lower prostatic zinc concentration than all other groups. Zinc concentrations were not statistically different between any of the other groups. Castration did decrease the prostatic tissue concentration of zinc, a known natural antibacterial factor. However, resistance to infection and resolution of infection were not correlated with prostatic tissue zinc concentrations in this experimental model. PMID- 1928908 TI - Respiratory tract distribution and bioavailability of spiramycin in calves. AB - Pharmacokinetic determinants of spiramycin and its distribution into the respiratory tract were studied in 2 groups of calves, 4 to 10 weeks old. Group-A calves (n = 4) were used to determine pharmacokinetic variables of spiramycin after IV (15 and 30 mg/kg of body weight) and oral administrations of the drug (30 mg/kg) and to measure distribution of spiramycin into nasal and bronchial secretions. Group-B calves (n = 4) were used to determine distribution of spiramycin into lung tissue and bronchial mucosa. Spiramycin disposition was best described by use of an open 3-compartment model. Mean (+/- SD) elimination half life was 28.7 +/- 12.3 hours, and steady-state volume of distribution was 23.5 +/ 6.0 L/kg. Bio-availability after oral administration was 4 +/- 3%. High and persistent concentrations of spiramycin were achieved in the respiratory tract tissues and fluids. Tissue-to-plasma concentration ratio was 58 for lung tissue and 18 for bronchial mucosa at 3 hours after spiramycin administration and 137 and 49, respectively at 24 hours. Secretion-to-plasma concentration ratio was 4 for nasal secretions and 7 for bronchial secretions, and remained almost constant with time. Thus, spiramycin penetrates well into the respiratory tract, although the value in bronchial secretions is lower than that in lung tissues and bronchial mucosa. Calculations indicate that a loading dose of 45 mg/kg, administered IV, followed by a maintenance dose of 20 mg/kg, IV, once daily is required to maintain active concentrations of spiramycin against bovine pathogens in bronchial secretions. PMID- 1928909 TI - Kinetic study of serum gentamicin concentrations in baboons after single-dose administration. AB - This study establishes preliminary pharmacokinetic data on the use of gentamicin sulfate administered IM to baboons. Serum concentrations greater than or equal to 12 micrograms/ml are generally agreed to cause toxicosis in human beings. On the basis of preliminary test results suggesting that the manufacturer's recommended dosage for dogs of 4.4 mg/kg of body weight caused potentially toxic serum concentrations, a dosage of 3 mg/kg was chosen to conduct a single-dose kinetic study in 6 baboons. Using a single-compartment model, the gentamicin serum half life for IM administration of 3 mg of gentamicin/kg was 1.58 hours, and serum concentrations remained below the potentially toxic concentrations reported for human beings. We suggest that a dosage of 3 mg/kg is safer than a dosage of 4.4 mg/kg administered IM to baboons. Minimal inhibitory concentrations for 2 Pseudomonas aeruginosa isolates were less than or equal to 1 micrograms/ml. On the basis of our measured elimination half-life of 1.58 hours, it is reasonable to suppose that dosing q24 h will be inadequate to maintain therapeutic serum concentrations. We calculate that serum concentrations will remain at or above our measured minimal inhibitory concentration for P aeruginosa (1 micrograms/ml) for 100% of the treatment time if the animal is dosed q 6h, 78% for dosing q 8h, and 52% for dosing q 12h. Therefore, we suggest 3 mg/kg, q 8h or q 6h as appropriate dosing schedules for the use of gentamicin sulfate administered IM to baboons. PMID- 1928910 TI - Use of corticosterone and ampicillin for treatment of Streptococcus faecalis infection in chickens. AB - Chickens were selectively bred for either high-antibody (HA) or low-antibody (LA) response to sheep erythrocytes. From 6 to 31 days after Streptococcus faecalis challenge exposure, LA-line chickens maintained a greater percentage of the prechallenge-exposure body weight and had lower heterophil-to-lymphocyte ratio than did HA-line chickens. The optimal dose of corticosterone (30 mg/kg of feed) was effective in maintaining postchallenge-exposure body weight greater than that of controls. Ampicillin (20 mg/d) alone was ineffective in almost all experiments. Treatment with 30 mg of corticosterone/kg of feed plus ampicillin resulted in increased body weight response to S faecalis infection when treatment was initiated 1 day before or 2 days after challenge exposure. Treatment with corticosterone was more effective in HA- than in LA-line chickens. Treatment before challenge exposure was more effective than treatment 2 days after challenge exposure. PMID- 1928911 TI - Characteristics of digital flexor tendon sheath fluid from clinically normal horses. AB - Physical, biochemical, and cytologic properties of synovial fluid from digital flexor tendon sheaths of clinically normal horses were investigated. Tendon sheath fluid was pale yellow, clear, and did not clot. Volume of fluid within a tendon sheath varied minimally, with a mean of 2.11 ml. Total erythrocyte counts were higher than values observed in normal equine joint fluid, whereas values for total leukocyte count (770 +/- 73 cells/mm3), viscosity (6.05 +/- 0.58 cs), and protein concentration (7.87 +/- 0.03 mg/ml) were similar to those in joint fluid. Large mononuclear cells were the predominant synovial fluid cell type. Mean hyaluronic acid concentration (0.74 +/- 0.02 mg/ml) and mucinous precipitate quality were lower than values in joint fluid. PMID- 1928912 TI - Cytologic, microbiologic, and biochemical analysis of bronchoalveolar lavage fluid obtained from 24 healthy cats. AB - Twenty-four healthy cats underwent bronchoscopy and bronchoalveolar lavage to determine the normal cytologic environment of the lower respiratory tract of cats. Initial screening to ensure the health of the study population included complete histories, physical examinations, thoracic radiography, CBC, serologic tests for feline leukemia virus, feline immunodeficiency virus, and occult heartworm, and sugar and Baermann fecal flotation. In 18 cats, protected catheter brush samples of airway secretions from the lavaged lung segment were taken for culture of aerobic and anaerobic bacteria and mycoplasma. Bronchial lavage fluid (5 sequential 10-ml aliquots of normal saline solution) was pooled and filtered with cotton gauze. The unspun sample was used for determination of a total nucleated cell count. Lavage fluid was cytocentrifuged and 500 cells/slide were scored for determination of the cellular differential. Activity of lactate dehydrogenase and concentrations of total protein and IgG within the supernatant were measured, and assays were performed to detect the presence of IgA and IgM. Complete histologic evaluation of the lavaged lung of each of 6 random-source cats was performed after differential cell counting revealed 18% eosinophils within bronchoalveolar lavage fluid recovered from this group. Alveolar macrophages were the predominant cells encountered; however, a quarter of all cells recovered were eosinophils. A significant relationship was not found between the abundance of eosinophils in the lavage fluid, and either isolation of aerobic bacteria, high total nucleated cell counts, total protein concentrations, or activity of lactate dehydrogenase. Histologic evaluation of the lungs of 5 of 6 random-source cats revealed normal lungs in 2 cats, and minimal abnormal change in 3 others. Evaluation of the lungs from 1 random source cat revealed acute, mild eosinophilic bronchiolitis. We conclude that large numbers of eosinophils may be retrieved from the bronchoalveolar lavage fluid of healthy cats. PMID- 1928913 TI - Resistance of population-B equine strongyles to thiabendazole, oxfendazole, and phenothiazine (1981 to 1987). AB - Critical tests were completed on foals (n = 15) naturally infected with benzimidazole (BZ)-resistant population-B strongyles during the period between 1981 and 1987. Thiabendazole at a dosage of 44 mg/kg was tested in 8 foals, oxfendazole at 10 mg/kg was tested in 4 foals, and phenothiazine at 55 mg/kg, cambendazole at 20 mg/kg, and fenbendazole at 5 mg/kg were tested in 1 foal each. Efficacies of thiabendazole, cambendazole, and fenbendazole against the 5 species of BZ-resistant small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocylus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus) were partial. Removals in the aggregate averaged 48%, 52%, and 68%, respectively, indicating continued resistance of the 5 species of small strongyles to thiabendazole, cambendazole, and fenbendazole. In contrast, oxfendazole was efficacious, removing an aggregate average of 95% of the 5 BZ-resistant species of small strongyles in the 4 foals. This apparent reversion to susceptibility to oxfendazole may be attributable to paucity of reference data (1 test foal) done in 1976. All 5 species of the BZ-resistant small strongyles had cross resistance to phenothiazine (38% aggregate removal), whereas 9 of the BZ-susceptible species were effectively (99%) removed. This suggests a similar mode of action between phenothiaznie and the BZ compounds. PMID- 1928914 TI - Efficacy of netobimin against Muellerius capillaris and resistant strain of digestive tract strongyles in dairy goats. AB - The efficacy of netobimin against digestive tract strongyles and the small lungworm Muellerius capillaris was tested in a dairy goat herd. The drenches were given orally at the rate of 20 mg/kg of body weight once, 10 mg/kg on 2 successive days, or 7.5 mg/kg on 3 successive days. Fecal egg counts and larval counts were done 8 days before and on the day of drenching; further counts were performed on postdrenching days 8 and 18. Two goats were necropsied, 1 on postdrenching day 5 and 1 on day 10 in the group treated on 3 successive days. The fecal egg counts were reduced by 44 to 79% depending on dosage on postdrenching day 18; the remaining worms were Trichostrongylus colubriformis. The larval counts of M capillaris were reduced by 72 to 92%, depending on dose. The reduction was significant in all the treated groups, compared with that in the control group. The use of netobimin at the dosage of 10 mg/kg given on 2 successive days or 7.5 mg/kg given on 3 successive days might be recommended to treat goats infected with Muellerius spp and digestive tract strongyles. PMID- 1928915 TI - Protective immunity to toxoplasmosis in pigs vaccinated with a nonpersistent strain of Toxoplasma gondii. AB - The RH strain of Toxoplasma gondii is highly virulent; 1 infective organism is uniformly lethal for mice. Three pigs inoculated SC with 10(3) tachyzoites of the RH strain developed fever, but otherwise remained normal, and T gondii was not demonstrated in their tissues by bioassay into mice. To determine whether vaccination with the RH strain could induce protective immunity to oral challenge with T gondii oocysts, 12 pigs were divided into 3 groups (A, B, C) of 4 pigs each. Pigs in groups A and B were inoculated IM with 10(6) tachyzoites of the RH strain and 4 pigs in group C served as uninoculated controls. Except for fever, the pigs remained clinically normal after inoculation with the RH strain and T gondii was not found by bioassay in mice of tissues from 4 pigs euthanatized 64 days after inoculation. Pigs in groups B and C were challenge-inoculated orally with 10(4) (4 pigs) or 10(5) (4 pigs) T gondii oocysts 72 days after vaccination with the RH strain. The previously uninoculated pigs developed fever, anorexia, and diarrhea from 3 to 8 days after the oocyst challenge. One of the 2 pigs given 10(5) oocysts became moribund because of toxoplasmosis and was euthanatized 9 days after inoculation. Pigs vaccinated with the RH strain remained free of clinical signs after challenge with oocysts. Results of the bioassays indicated that fewer tissue cysts developed in the RH strain-vaccinated pigs than in the previously uninoculated control pigs. PMID- 1928916 TI - Tumor necrosis factor as a potential mediator of acute metabolic and hormonal responses to endotoxemia in calves. AB - The effects of coliform endotoxin (E) and recombinant bovine tumor necrosis factor alpha (TNF) were compared with respect to clinical signs of disease and changes in plasma metabolite and pituitary and pancreatic hormone concentrations in calves. In addition, changes in plasma TNF concentration during each challenge exposure were quantitated by use of radioimmunoassay. Healthy Holstein bull calves with mean body weight of 90 kg were each given, in order, on different days, saline solution (5.0 ml, IV, day 1, n = 4), E (type 055:B5, 1.0 micrograms/kg of body weight IV, day 2, n = 4) and TNF (5.0 micrograms/kg IV, day 9, n = 3). Jugular venous blood samples, rectal temperature reading, and PCV were obtained at hourly intervals before (2 hours) and after challenge exposure. The PCV increased (P less than 0.05) after E and TNF administrations for the first 5 hours, then returned to normal in calves given E, but decreased and remained low in calves given TNF through 24 hours. Plasma triglyceride and nonesterified free fatty acids concentrations were increased through 10 hours (P less than 0.05) after E administration, whereas triglyceride and nonesterified free fatty acids concentrations were not significantly affected by TNF administration. Increase in blood glucose concentration at 1 hour after administration of E and TNF was followed by prolonged hypoglycemia that lasted through 6 hours. Changes in plasma insulin concentration paralleled the observed changes in glucose concentration, initially increased at 2 hours after E and TNF (P less than 0.05) administrations, but then tended to decrease below control values thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928917 TI - Effects of mechanical and pharmacologic manipulations on portal pressure, central venous pressure, and heart rate in dogs. AB - Central venous pressure (CVP), portal pressure (PP), and heart rate (HR) were monitored in 6 female, sexually intact, middle-age Beagles during temporary portal vein obstruction, anesthetic recovery, abdominal bandaging, and propranolol administration. Intraoperative baseline PP was 7.3 mm of Hg (+/- 1.7 SD). Portal pressure was significantly increased throughout portal vein occlusion, but returned to baseline values 2 minutes after release of the ligature. Central venous pressure was significantly decreased throughout portal vein occlusion, but did not differ significantly from baseline values 3 minutes after release of the portal vein ligature. Portal pressure increased significantly (8 +/- 3.3 mm of Hg) over baseline values after application of an abdominal bandage; however, CVP did not change significantly. During postoperative monitoring, CVP and PP did not change significantly from respective 18-hour mean postoperative values in resting dogs. At 60 and 75 minutes after surgery, heart rate was significantly increased over the 18-hour mean. Portal pressure and CVP, respectively, were significantly increased over intraoperative baseline values in the first hour and the first 8 hours after surgery. Postoperative CVP and HR were significantly correlated. Individual measurements of PP in dogs that were abdominal pressing during barking or defecation were significantly increased (9 +/- 3 mm of Hg) above measurements taken after cessation of abdominal press. Portal pressure measurements in standing dogs decreased 7.5 +/- 2 mm of Hg, compared with measurements of the same dog in lateral recumbency. Central venous pressure was inaccurate in dogs performing abdominal press. Portal pressure did not decrease significantly from baseline after injection of propranolol (2 mg/kg, IV).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928918 TI - Functional analysis of ectopic parathyroid activity in cats. AB - The ability of ectopic parathyroid tissue to support calcium homeostasis was evaluated by measuring serum concentrations of calcium, phosphorus, albumin, magnesium, and parathyroid hormone before and for 12 weeks after bilateral thyroparathyroidectomy in 14 cats. During the immediate postoperative period, significant decrease was observed in serum calcium, magnesium, and parathyroid hormone (PTH) concentrations. Serum PTH concentration remained subnormal and did not significantly increase during the 12-week observation period. Despite persistent hypoparathyroidism, serum calcium and magnesium concentrations gradually increased. Ectopic parathyroid tissue is not capable of maintaining normal serum calcium concentration immediately after thyroparathyroidectomy. Serum calcium concentration gradually normalizes after thyroparathyroidectomy, apparently by means of a PTH-independent mechanism. PMID- 1928919 TI - Pigment epithelial function in canine retina. AB - The lateral distribution and temporal changes in the eye standing potential of 15 dogs with normal eyes (as determined by use of an ophthalmoscope and electroretinography) were measured by use of noninvasive methods. The standing potential was converted to an alternating potential by controlled eye movement. The light peak occurred 6 minutes after a stimulus intensity increase of 4 log units. The ratios of the highest measured voltage after the light step divided by the voltage measured immediately before the light step ranged from 1.27 to 2.07 (mean 1.74 +/- SEM, 0.064). The responses typically decayed slowly after the light peak. The potential after the light peak did not return to prelight step values during the observation period. The field potential of the standing potential decreased nonlinearly in temporal direction from the outer canthus. PMID- 1928920 TI - Quantitative evaluation of the remodeling response of the proximal sesamoid bones to training-related stimuli in Thoroughbreds. AB - Eight untrained 2-year-old Thoroughbred horses were used in a study of the remodeling response of the proximal sesamoid bone (PSB) to training-related stimuli. Two horses each were assigned to 1 of 4 groups: group 1, untrained, pasture turnout (control); group 2, modified-classically trained, dirt track; group 3, classically trained, dirt track; and group 4, classically trained, wood chip track. Horses were given fluorochromic bone labels every 28 days during training. All horses were euthanatized after 5 months of training, and the proximal sesamoid bones (PSB) were removed. A midsagittal section of bone 85- to 95-microns thick was prepared for histomorphometric analysis by use of computerized image analysis and epifluorescent microscopy. Porosity (percent), trabecular width (micrometer), extent of anisotropy (percent), mineralizing surface (percent), fractional mineralizing surface (percent), and mineral apposition rate (micrometers per day) were determined at 5 circular regions of each specimen. Region 1 was located within the apex of the PSB, regions 2, 3, and 4 were subjacent to the subchondral plate, and region 5 was within the basilar articular margin. Data were pooled to allow comparison by training group and by region. The PSB from horses trained on dirt tracks (groups 2 and 3) had significantly (P less than 0.05) lower porosities and greater trabecular width, compared with the control group. The PSB from all training group specimens had significantly larger mineralizing surfaces than control group specimens. The fractional mineralizing surface revealed a rapid and vigorous response of the endosteal surface of the PSB in horses trained on dirt tracks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928921 TI - Effect of dietary protein on functional, morphologic, and histologic changes of the kidney during compensatory renal growth in dogs. AB - Two diets similar in caloric density and mineral content, but markedly different in protein content, were used to study the effects of dietary protein on renal function and morphologic and histopathologic changes in dogs that had functional renal tissue reduced by seven-eights nephrectomy. The effects of moderate protein intake (MPrI = 15% protein; dry-matter basis) and high-protein intake (HPrI = 31% protein; dry-matter basis) were studied for the initial 7 months (period 1 [P1]) after renal mass reduction. Diets were then switched between groups during the following 7 months (period 2 [P2]) to evaluate the effects of increased or decreased protein intake. The HPrI caused significantly (P less than 0.05) greater glomerular filtration rate (GFR) and renal growth than did MPrI during P1. Dogs that maintained HPrI during P1 and MPrI during P2 (group 1) had significant (P less than 0.05) reduction in GFR during P2. Dogs that maintained MPrI during P1 and HPrI during P2 (group 2) had significant (P less than 0.05) improvement in GFR and renal growth during P2. At the end of the study, renal reserve was evaluated in both groups of dogs before and after group 1 was returned to HPrI for 2 weeks. During this 2-week feeding trial, group-1 dogs had marked improvement in renal reserve, relative to group 2, and GFR increased to the terminal P1 values. Results indicate a possible residual benefit from HPrI during the early phase of compensatory renal growth in the form of functional compensatory memory to HPrI. The severity of renal lesions was indistinguishable between dogs of dietary groups during both study phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928922 TI - Reversibility of furazolidone-induced cardiotoxicosis in ducklings. AB - Furazolidone cardiotoxicosis was induced in 2 groups (FZ and FZ-CR groups) of newly hatched male Pekin ducklings (100/group) by feeding a ration containing 650 mg of furazolidone/kg of feed (ppm) for 28 days. A third group (control ration, CR group; n = 100) was fed the same ration without furazolidone. On day 28, the control ration was initiated for the FZ-CR group initially given the furazolidone containing ration, to allow recovery from the effects of the drug, whereas ducklings of the FZ group continued to consume the furazolidone-containing ration. Biweekly, beginning with week 4, ducklings were euthanatized to assess severity of gross lesions and to obtain sections of myocardium for histologic and ultrastructural examination. Clinical evidence (increased weight gain, increased feed consumption, decreased mortality, reduced prevalence of palpable ascites) of regression of cardiotoxicosis of ducklings of the FZ-CR group was nearly complete by day 56 (28 days after cessation of furazolidone intake). Likewise, regression of gross lesions, as measured by overall prevalence of gross lesions, left ventricular volume, and ascites prevalence and severity, were also essentially complete by day 56. Myofibrillar lysis was not seen in sections from the heart (examined ultrastructurally) obtained from ducklings of the CR group that were euthanatized on day 28, 56, or 98. Myofibrillar lysis was detected in all ducklings (4/4) fed furazolidone (FZ and FZ-CR groups) and euthanatized on day 28. Myofibrillar lysis was not seen in the heart of ducklings of the FZ-CR group that were euthanatized on day 56 or 98. Myofibrillar lysis was detected in the heart from all ducklings of the FZ group that were euthanatized on day 56.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928923 TI - Effects of amnion and live yeast cell derivative on second-intention healing in horses. AB - Equine amnion and live yeast cell derivative were evaluated as a biological dressing and as a topical wound medicament respectively, in the treatment of granulating wounds of the distal portion of the limbs of horses. Wounds measuring 2.5 x 2.5 cm were created on the dorsomedial aspect of the metacarpal and metatarsal region of all 4 limbs of 9 horses. Each wound was assigned randomly to 1 of 3 treatment groups: group C, treated with a nonadherent bandage as a control; group A, treated with amnion beneath a nonadherent bandage; and group L, treated with live yeast cell derivative beneath a nonadherent bandage. Rates of contraction and epithelialization were not significantly different among groups. Percentage of epithelialization for group A was significantly greater throughout the study than for the other groups. Number of days to complete healing was significantly less in group A and significantly greater in group L than in group C. Incidence and severity of exuberant granulation tissue were significantly less in group A than in the other 2 groups. Group L had more frequent and severe cases of exuberant granulation tissue than the other 2 groups. PMID- 1928924 TI - Antibiotic and sulfonamide agents in bob veal calf muscle, liver, and kidney. AB - During the fiscal year 1988, USDA-FSIS detected 3,095 antimicrobial violations in bob veal calves, using the calf antibiotic and sulfonamide test. Of the 3,095 carcass submissions involved, 945 were tested further to identify the causative agents. The results of tests on the available kidney, liver, and muscle specimens are reported. Kidney specimens yielded a specific agent most often (71.2%), with neomycin (42.6%) being cited most among agents found in kidneys. Neomycin was found less frequently in liver (4.5%) and muscle (0.2%). Among all tissues, unidentified microbial inhibitors were either the largest or second largest category found (kidney, 10.5%; liver, 27.1%; muscle, 7.8%), and no other agent exceeded 7.0% (streptomycin in kidney). The proportion of liver and muscle specimens that had unidentified microbial inhibitors is particularly important because the next most common classes were streptomycin in liver at 5.5% and sulfamethazine in muscle at 2%. The frequency of unidentified microbial inhibitors may justify the addition of tests to the FSIS battery for identification of agents. Not all tissues were tested for sulfonamides, hence these agents are likely to have been underreported. Less than 10% of the muscle specimens evaluated yielded an agent, suggesting most calf antibiotic and sulfonamide test-positive carcasses may have been safe with regard to residues in meat, although organs might have been adulterated. Specimens for verification were not selected completely randomly from the population of all calf antibiotic and sulfonamide test-positive animals and calves selected for testing were not chosen strictly by random sampling; therefore, extrapolation of the contents of this report to the bob veal calf industry must be done with caution. PMID- 1928925 TI - Anesthetist combines art, science, a day in the life of a nurse. PMID- 1928926 TI - VA technicians assist nurses. PMID- 1928927 TI - Search for excellence 1991. PMID- 1928928 TI - Nurse Education Act is vital. PMID- 1928929 TI - RNs ready to reform health care. PMID- 1928930 TI - Congress on Nursing Economics meets. PMID- 1928931 TI - Where is nursing's leading edge? PMID- 1928932 TI - Good record is good defense. PMID- 1928933 TI - Nurses week--time to celebrate! PMID- 1928934 TI - Wisdom over time. PMID- 1928935 TI - Medicare fee schedule recommended. PMID- 1928936 TI - Progress on a cognitive-motivational-relational theory of emotion. AB - The 2 main tasks of this article are 1st, to examine what a theory of emotion must do and basic issues that it must address. These include definitional issues, whether or not physiological activity should be a defining attribute, categorical versus dimensional strategies, the reconciliation of biological universals with sociocultural sources of variability, and a classification of the emotions. The 2nd main task is to apply an analysis of appraisal patterns and the core relational themes that they produce to a number of commonly identified emotions. Anger, anxiety, sadness, and pride (to include 1 positive emotion) are used as illustrations. The purpose is to show the capability of a cognitive-motivational relational theory to explain and predict the emotions. The role of coping in emotion is also discussed, and the article ends with a response to criticisms of a phenomenological, folk-theory outlook. PMID- 1928937 TI - War-related stress. Addressing the stress of war and other traumatic events. AB - A task force on war-related stress was convened to develop strategies for prevention and treatment of psychological, psychosocial, and psychosomatic disorders associated with the Persian Gulf War and other extreme stressors facing communities in general. The task force focused on the return home, reunion, and reintegration of service personnel with their families and work. Although the Persian Gulf War was won with relative ease, negative psychological sequelae may develop in some individuals because of the stress of war, family disruption, financial difficulty, and changes in family routines. Typical stress reactions and modes of coping that are usually unsuccessful or destructive were outlined, and suggestions were made for monitoring these. In addition, guidelines for successful coping were developed. Special attention was given to children's reactions and needs. Recommendations were made for outreach and intervention on the policy, systems (e.g., schools, businesses, governmental agencies), family, and individual levels. PMID- 1928938 TI - Temperamental factors in human development. AB - The initial dispositions to approach or to avoid unfamiliar events are 2 temperamental characteristics of children--among the many that have been described--that appear to be moderately stable over time and associated with distinct, physiological profiles that may be under partial genetic control. The display of high versus low levels of both motor activity and crying to unfamiliar in 4-month-old infants predicts these 2 temperamental profiles in the 2nd year. This fact implies, but does not prove, that variation in the excitability of those brain areas that mediate motor activity and crying participates in the actualization of the temperamental categories called inhibited and uninhibited to the unfamiliar. PMID- 1928939 TI - If it's not left, it's right. Electroencephalograph asymmetry and the development of emotion. AB - Recent studies suggest that an initial component involving stimulus evaluation may precede subsequent steps in the generation of emotion. This article presents a model for the development of emotion that involves an initial decision of approach or withdrawal, which results in motor programs, including facial expression, that facilitate either approach or withdrawal. With development, more complex emotions arise, as products of these basic initial responses and interaction with the environment. Evidence is presented that suggests that there are brain asymmetries (as measured by scalp recorded EEG activity) localized to the frontal region that are associated with the generation of emotion in infants. Variability in the pattern of EEG asymmetry between infants may be an important marker of differences in temperament. PMID- 1928940 TI - The U-shaped curve of concern. PMID- 1928941 TI - Asthma: a solution to half the puzzle? PMID- 1928942 TI - Resurgent tuberculosis in New York City. Human immunodeficiency virus, homelessness, and the decline of tuberculosis control programs. AB - The resurgence of tuberculosis in New York City has been largely attributed to the acquired immune deficiency syndrome (AIDS) epidemic. However, historical events predating the advent of AIDS and worsening economic and social conditions, including a rise in homelessness, have contributed significantly to the increase. We prospectively studied 224 consecutive patients with tuberculosis admitted to a large public hospital in New York over the first 9 months of 1988. Initial assessment included medical status, human immunodeficiency virus (HIV) risk factors, and detailed social information, including substance abuse history and housing status. All patients were tracked after discharge to determine compliance and cure rates. Tuberculosis patients were predominantly male (79%), with high rates of alcohol use (53%), intravenous drug and/or "crack" cocaine use (64%), and homelessness or unstable housing (68%). Half the patients had AIDS or AIDS related complex (ARC) or were HIV antibody positive. A total of 178 patients were discharged on tuberculosis treatment, but 89% of these were lost to follow-up and failed to complete therapy. Of the 178 discharged patients, 48(27%) were readmitted within 12 months with confirmed active tuberculosis. Of these patients, 40 were discharged on treatment and at least 35 were again lost to follow-up. In a multivariate regression model noncompliance was significantly associated with the absence of AIDS or ARC (p less than 0.001), homelessness (p less than 0.005), and alcoholism (p less than 0.05). Because HIV infection and tuberculosis converge in a subpopulation with high rates of substance abuse and homelessness, the problem of ensuring treatment compliance may grow considerably in the future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928943 TI - Increased mortality and tuberculosis treatment failure rate among human immunodeficiency virus (HIV) seropositive compared with HIV seronegative patients with pulmonary tuberculosis treated with "standard" chemotherapy in Kinshasa, Zaire. AB - To evaluate their treatment outcomes 170 human immunodeficiency virus (HIV) seropositive and 597 HIV seronegative patients with active pulmonary tuberculosis (TB) treated for 1 yr with "standard" chemotherapy, including streptomycin, isoniazid, and, in most cases, thiacetazone, were traced at completion of therapy. All 582 survivors were invited for reevaluation, and 385 patients, of whom 82 (21.3%) were HIV seropositive, were evaluated. Of those, 325 consenting patients, of whom 67 (20.6%) were HIV seropositive, were followed for 12 months. One year after TB had been diagnosed 47 (31.3%) of the 150 HIV seropositive and 22 (4.4%) of the 501 HIV seronegative patients traced had died (p = 10(-6]. During the subsequent year the mortality of 67 HIV seropositive patients (26.3/100 patient-years) was higher than that of the 303 HIV seronegative patients (2.2/100 patients-years, p = 10(-6]. HIV seropositive patients had a higher overall TB therapy failure rate 24 months after the diagnosis of TB than did HIV seronegative patients (21.1/100 patient-years versus 8.1/100 patient years, p = 0.002), mainly because their relapse rate of pulmonary TB (18.1/100 patient-years) was higher than that of HIV seronegative patients (6.0/100 patient years, p = 0.03). Given their higher relapse rate after 1 yr of "standard" chemotherapy, the public health impact of routine maintenance therapy in HIV seropositive patients with pulmonary TB who complete such therapy should be assessed in comparison to the introduction of rifampicin-based short-course antituberculosis chemotherapy in developing countries. PMID- 1928944 TI - Epidemiologic patterns of upper respiratory illness and Pneumocystis carinii pneumonia in homosexual men. AB - The relationship between self-reported upper respiratory illness symptoms (URI) and human immunodeficiency virus Type 1 (HIV-1) was examined in homosexual men using semiannual visits from 1984 to 1988. Temporal and geographic patterns of Pneumocystis carinii pneumonia (PCP) diagnosis in these men during the same time period are also described. URI, including acute sinusitis, was reported more often by 916 HIV-1-seropositive participants than by 2,161 seronegative participants (32.21 versus 28.86% p less than 0.001). For 387 seropositive subjects who progressed to acquired immunodeficiency syndrome (AIDS), the proportion reporting URI peaked one visit pre-AIDS at a level significantly higher than matched control subjects (0.45 versus 0.28, p less than or equal to 0.001). The peak was higher for those with PCP as an initial diagnosis. Reported URI peaked in winter and troughed in summer, and PCP diagnosis rates peaked and troughed 4 months later, respectively. Cities with the highest reported rates of URI also had the highest proportions of AIDS cases with PCP as an initial diagnosis. No temporal or geographic patterns were observed for other HIV-1 related symptoms or non-PCP AIDS diagnoses. These patterns suggest the possibility of a person-to-person transmission of P. carinii similar to that of other respiratory pathogens, which would imply a need to consider stricter methods to prevent nosocomial transmission of this pathogen in inpatient and outpatient settings. Further investigation of these issues is needed. PMID- 1928945 TI - Effect of aerosolized pentamidine prophylaxis on the diagnosis of Pneumocystis carinii pneumonia by induced sputum examination in patients infected with the human immunodeficiency virus. AB - This study assessed the effect of aerosolized pentamidine prophylaxis on the clinical presentation and diagnostic sensitivity of induced sputum examination for Pneumocystis carinii pneumonia. Between January 1, 1988 and October 27, 1990, 348 induced sputum examinations were performed as the initial diagnostic procedure for P. carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). Medical records were reviewed for all induced sputum examinations, and the study group consisted of patients who either had not received prophylactic therapy (n = 193) or had received aerosolized pentamidine prophylaxis (n = 126). A total of 29 induced sputum examinations in patients receiving either other prophylactic regimens or ongoing therapy for previously documented P. carinii pneumonia were excluded from the study group. A total of 72 consecutive episodes of P. carinii pneumonia were subsequently documented by induced sputum examination (n = 54), bronchoalveolar lavage (n = 16), thoracocentesis (n = 1), or autopsy (n = 1). A total of 44 episodes occurred in patients who had not received antipneumocystis prophylaxis, and 28 episodes occurred in patients who had received aerosolized pentamidine. Of patients capable of producing a sputum specimen for analysis, induced sputum examination had a significantly lower diagnostic yield of 64.3% in patients who had received aerosolized pentamidine prophylaxis compared with 92.3% in patients who did not receive prophylaxis (p less than 0.02, Fisher's exact test). When the data were analyzed on an intention to treat basis, although there was a trend suggesting a lower overall yield in the aerosolized pentamidine patients, the difference was not statistically significant (64.3 versus 81.8%, p = 0.17, Fisher's exact test).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928946 TI - Japanese summer-type hypersensitivity pneumonitis. Geographic distribution, home environment, and clinical characteristics of 621 cases. AB - A survey of hypersensitivity pneumonitis in Japan was carried out by nationwide questionnaire. A total of 835 cases of hypersensitivity pneumonitis was recognized during the last decade from 1980 to 1989. Of the 835 cases, 621 (74.4%) were summer-type hypersensitivity pneumonitis. The number of cases diagnosed doubled in the latter half of the 10-yr period. The residence of the patients was mostly in the western and southern parts of the country; the northernmost incidence was in Akita Prefecture at a latitude of 40 degrees north. Of the patients 86% experienced initial symptoms from June to September with a peak in July. Female patients were 2.0 times as numerous as male patients, probably as a result of more exposure to the offending antigen at home since 39.8% of the patients were female homemakers without an outside occupation. The frequency of family occurrence was 23.8%. The mean age of the patients' houses was 20.5 yr after building, and more than half had unsanitary conditions, such as shady, damp, or poorly ventilated rooms. Serum anti-Trichosporon cutaneum antibody activities were positive in 260 (99.2%) of the 262 cases examined. We conclude that summer-type hypersensitivity pneumonitis occupies the majority of hypersensitivity pneumonitis in the country and that to prevent the disease concentrated attention should be given to the home environment from the viewpoint of environmental medicine. PMID- 1928947 TI - Heritability of ventilatory function in smoking and nonsmoking New Mexico Hispanics. AB - Familial aggregation of ventilatory function has been described in several populations, but the effects of age and cigarette smoking on the extent of aggregation have not been well characterized. We used data from a survey of a Hispanic population in New Mexico to obtain estimates of heritability for FVC and FEV1 as percentages of predicted value. Product-moment correlations for FVC of spouse pairs were 0.18 (n = 90 pairs) if neither smoked, 0.013 (n = 45 pairs) if only the wife smoked, 0.18 (n = 118 pairs) if only the husband smoked, and -0.04 (n = 83 pairs) if both smoked. Correlations for FEV1 of spouse pairs were similar. Because parent-child correlations did not vary with sex, we calculated product-moment correlations from the pooled data. The parent-child correlations for nonsmoking parents with nonsmoking children 6 to 17 yr of age and living in the same house were 0.16 (n = 335 pairs) and 0.17 for FVC and FEV1, respectively. For parents whose children were 25 yr of age or older, the parent-child correlations for those living in different houses were 0.37 (n = 63 pairs) for FVC and 0.40 for FEV1 if neither smoked, and 0.24 (n = 27 pairs) for FVC and 0.14 for FEV1 if both smoked. Heritability estimates, estimated by path analysis, were 0.43 for FVC and 0.42 for FEV1 if neither family member smoked and 0.65 for FVC and 0.44 for FEV1 if both family members smoked. We conclude that there is a moderate degree of heritability of FVC and FEV1 with no substantial change based on age or smoking status. PMID- 1928948 TI - Asthma, hay fever, and phlegm production associated with distinct patterns of allergy skin test reactivity, eosinophilia, and serum IgE levels. The Normative Aging Study. AB - We investigated the relationship of three phenotypic markers of atopy (allergy skin test reactivity, serum IgE level, and eosinophilia) to the prevalence of respiratory symptoms in 1,071 middle-aged and older men participating in the Normative Aging Study. Participants had all been health screened at the onset of the study in the 1960s to exclude individuals with asthma or other chronic respiratory diseases. Respiratory symptoms were grouped into three categories: asthma (adult onset) and other wheezing syndromes; cough and phlegm production; and hay fever. Multivariate logistic regression models were utilized to assess the independent relationship of each phenotypic marker to symptom prevalence adjusted for age, cigarette smoking, and the competing influence of the other markers. In this population, the prevalence of each symptom increased with serum total IgE concentration, this relationship being strongest for asthma. Skin test positivity (greater than or equal to 5 mm induration to one or more aeroallergens) was strongly associated with hay fever but was not significantly associated with symptoms of wheeze or cough and phlegm. Eosinophilia was associated with asthma and with phlegm production. The association of eosinophilia with phlegm production was present in skin test-negative as well as skin test-positive subjects and remained significant even after current smokers and individuals with asthma or hay fever were excluded. These data support the concept that asthma and hay fever are related to different immunologic host factors as reflected by expression of atopy phenotypes. Future investigations of immunologic factors in respiratory disease susceptibility should include, at a minimum, an assessment of all three phenotypic markers of atopy. PMID- 1928949 TI - The inhibitory effect of nebulized albuterol on the early and late asthmatic reactions and increase in airway responsiveness provoked by inhaled allergen in asthma. AB - It is widely held that inhaled beta 2-adrenoceptor agonists inhibit the early asthmatic response (EAR) but not the late response (LAR) or attendant increase in bronchial responsiveness. In this study of 10 atopic asthmatic subjects, we have investigated the effects of a high dose of nebulized albuterol (2.5 mg) on the allergen-provoked EAR, LAR, and increase in histamine responsiveness. In a randomized blinded fashion, study subjects inhaled the following combinations: albuterol followed 10 min later by allergen, placebo followed by allergen, albuterol followed by saline (albuterol, placebo, and control study periods, respectively). Airway caliber was measured as FEV1 and followed at regular intervals for 7.5 h postallergen. Bronchial responsiveness to histamine was measured and recorded as the PC20 value before and at 1.5, 3.5, 5.5, and 7.5 h after allergen or control challenge. During the placebo study period, allergen challenge caused mean 29.6 +/- 6.4 and 24.4 +/- 6.4% falls in FEV1 at 20 min and 7.5 h, respectively (both p less than 0.05), and a progressive decrease in PC20 amounting to a geometric mean of 1.9 doubling dilutions at 7.5 h (p less than 0.05). Albuterol followed by allergen resulted in a 13.1 +/- 2.2% increase in FEV1 prior to allergen followed by abolition of the EAR and inhibition of the LAR with only a 9.2 +/- 3.5% fall in FEV1 at 7.5 h, significantly different from that of placebo at 7.5 h (p = 0.048). Similarly, PC20 histamine fell by only 0.64 doubling dilutions at 7.5 h, not significantly different from baseline values but different from placebo values (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928950 TI - Strain-related differences in airway smooth muscle and airway responsiveness in the rat. AB - The purpose of this study was to evaluate the possible role of the quantity of airway smooth muscle (AWSM) as a determinant of differences in responsiveness between inbred rat strains. To do this, we studied several batches of 8- to 10-wk old Lewis and Fisher 344 rats. Animals were anesthetized intraperitoneally with pentobarbital (30 mg/kg) and xylazine (7 mg/kg). The peak value of pulmonary resistance (RL) was measured after progressively doubling concentrations of inhaled aerosolized methacholine (MCh). The MCh concentration required to double RL (EC200RL) was calculated as an index of airway responsiveness. Fisher rats were significantly more responsive than Lewis, and the interstrain variability in responsiveness was significantly greater than the intrastrain variability. Additional animals from the less responsive Lewis strain (n = 8) and the more responsive F344 strain (n = 11) were killed immediately after measurement of responsiveness, and AWSM was quantitated as a fraction of total lung tissue using a point-counting technique. F344 rats were again significantly more responsive than Lewis rats (EC200RL geometric mean: 0.72 versus 2.16 mg/ml, p less than 0.005). F344 rats also had significantly more AWSM than did Lewis rats (3.22 +/- 0.176 versus 2.48 +/- 0.185%, mean +/- SE, p less than 0.001). We conclude that highly inbred Fisher rat strains characteristically exhibit a degree of airways responsiveness greater than that of the Lewis strain and that the quantity of AWSM may be an important determinant of interstrain differences. PMID- 1928951 TI - Effects of aminophylline on respiratory muscle interaction. AB - We studied the effects of aminophylline on respiratory muscle interaction during quiet breathing by measuring (1) changes in rib cage and abdominal cross sectional area, (2) tidal volume, (3) abdominal and esophageal pressure, (4) diaphragm and parasternal intercostal electromyogram (EMG) and parasternal intercostal intramuscular pressure, and (5) triangularis sternl and transversus abdominis EMG, in 14 supine anesthetized dogs. Measurements were done before and 5 and 10 min after administration of progressively increasing doses of aminophylline, reaching a total dose of 5, 10, 20, 40, and 80 mg/kg. In 12 of 14 dogs after aminophylline administration, quiet inspiration became biphasic, or if inspiration was already biphasic under control conditions, the first phase was clearly enhanced after aminophylline administration. Biphasic inspiration was defined as an inspiratory pattern in which rib cage and abdominal expansion showed two distinct phases. First, the onset of inspiration was characterized by a sudden increase in rib cage cross-sectional area often associated with a decrease in abdominal dimensions. During this initial part the parasternals and the diaphragm were electrically silent, confirming that it was achieved by relaxation of expiratory muscles. Further inspiration occurred predominantly through expansion of the abdomen. In the first phase, a pressure drop in the parasternal intercostals was present, presumably due to passive shortening of these muscles caused by expiratory muscle relaxation. On the average, 42 +/- 28% of the rib cage expansion was due to expiratory muscle relaxation at a dose of 80 mg/kg versus 17 +/- 21% under control conditions (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928952 TI - Maximal relaxation rate of inspiratory muscle can be effort-dependent and reflect the activation of fast-twitch fibers. AB - We have measured the normalized maximal relaxation rate (MRR, % pressure loss/10 ms) of esophageal and transdiaphragmatic pressures in five normal subjects who performed unoccluded shifts from FRC, with the peak pressure varying between 10 and 100% of each subject's maximum. MRR was computed as the maximal rate of decay of pressure divided by the peak pressure, with units of %pressure loss/10 ms. We observed that MRR became progressively faster as sniff peak pressure increased in amplitude above 10% maximum. In four subjects this trend was most marked for sniffs of less than 40% maximal pressure, with little change as peak pressure increased further. In a fifth subject this trend continued across the full range of pressure. Thus, MRR may be an effort-dependent variable during voluntary inspiratory maneuvers. We postulate that sniff MRR becomes faster with increasing peak pressure because of progressive activation of fast-twitch type II muscle fibers. The findings of this study suggest that erroneous conclusions about the significance of slowing of sniff MRR with fatigue may be made if MRR is determined from voluntary efforts with a peak pressure of less than 60% of control maximum, as may occur with fatigue. PMID- 1928953 TI - The effects of varying inflation and deflation pressures on the maximal expiratory deflation flow-volume relationship in anesthetized rhesus monkeys. AB - Deflation flow-volume curve analysis is a pulmonary function test sensitive to small airways dysfunction that is suitable for use in infants and children who are intubated. This test relies upon deflation flow-volume (DFV) curve analysis, which is a technique to obtain maximal expiratory flow-volume curves (MEFV) by forced deflation of the lungs in infants who are intubated. The method mimics the voluntary forced flow-volume curves that adults and older children undertake. We studied 10 anesthetized male Rhesus monkeys of the same weight as human infants but developmentally equivalent to older children. We reviewed the effects on forced deflation vital capacity (DVC) and flows at various subdivisions of vital capacity (PEF, MEF50, MEF25, MEF10) of systematically varying the required inspiratory and deflation pressure during the course of 56 consecutive deflation maneuvers. Inflation pressures of +40 and +50 cm H2O caused a marked but transient bradycardia along with a (probably spurious) short-lasting fall to 89% mean arterial oxygen saturation (SaO2). Increasing positive and negative pressures increased DVC and expiratory flows. The highest mean DVC was 75.6 +/- 1.3 ml/kg, PEF was 128.0 +/- 3.5, MEF50 was 85.9 +/- 2.2, MEF25 was 74.3 +/- 1.9, and MEF10 was 38.5 +/- 2.9 ml/kg/s, all obtained at the pressure gradient of 90 cm H2O (+50/-40 cm H2O) at the start of the deflation maneuver. At this gradient, the intraindividual coefficients of variation were: DVC = 0.8%, PEF = 3.1%, MEF50 = 2.2%, MEF25 = 2.1%, MEF10 = 5.4%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928954 TI - Repeated vital capacity measurements as predictive parameters for mechanical ventilation need and weaning success in the Guillain-Barre syndrome. AB - In Guillain-Barre syndrome (GBS), respiratory failure is a life-threatening complication, and its occurrence may be difficult to predict. We studied prospectively 10 patients with GBS by serial measurements of pulmonary function and arterial blood gases from the the time they were admitted to hospital. Five patients developed respiratory failure and had to be intubated, whereas the other five developed no ventilatory impairment. VC measurements were very useful in predicting respiratory failure several days before intubation. In patients who were eventually intubated, VC decreased during the 48 h preceding the occurrence of respiratory failure and intubation, which was required when VC was 15.2 +/- 3.7 ml/kg body weight (BW). In nonintubated patients, VC was stable and greater than 40 ml/kg BW. In addition, VC measurements allowed us to determine the beginning of the weaning procedure (no weaning trial could be performed successfully when VC was less than 7 ml/kg BW), to rationally follow its course, and to choose the time for extubation, i.e., when VC was greater than 15 ml/kg BW. PMID- 1928955 TI - Hemodynamic effects of 1:2 ECG-coupled jet ventilation in the dog. A comparison with other modes. AB - In 16 closed-chest dogs the hemodynamics of ECG-coupled jet ventilation (JV) with frequencies of 1:1 (one breath for each cardiac systole) and 1:2 (one breath for every other cardiac systole) were compared to noncoupled JV and intermittent positive-pressure ventilation (IPPV). Cardiac output was similar during 1:2 coupling (1.6 +/- 0.2 L/min) and IPPV (1.6 +/- 0.2 L/min) but decreased during 1:1 coupling (1.2 +/- 0.2 L/min) and noncoupled JV (1.3 +/- 0.2 L/min), p less than 0.05. During 1:2 coupling and IPPV, systemic arterial and transmural left atrial pressures were increased, and pulmonary artery, pericardial, and right atrial pressures were decreased in comparison to the other JV modes. Pulmonary blood volume was preserved during 1:2 coupling but decreased during 1:1 coupling and noncoupled JV. Coupling at 1:2 preserves output by maintaining left ventricular preload via a decrease in right atrial pressure and subsequent maintenance of systemic venous return. PMID- 1928956 TI - The language of breathlessness. Use of verbal descriptors by patients with cardiopulmonary disease. AB - The main objective of the present study was to test the hypothesis that patients with cardiopulmonary disease can reliably identify different sensory qualities of their experience of breathlessness. A secondary aim was to examine whether there was any relationship between such specific descriptors of the sensation of breathlessness and a patient's clinical diagnosis. A randomly ordered list of 45 descriptors of breathing discomfort related to exertion was administered on two occasions to 208 patients with cardiopulmonary disease; patients identified the descriptors that applied to their own experience. A total of 169 patients were considered reliable in that their responses were repeatable between questionnaires; there was evidence that an individual's reliability could be assessed by asking repeat questions within a questionnaire. With these patients, individual descriptors generated different degrees of yes and no response and were answered with a variable consistency, suggesting that some questions may be more useful than others in discriminating between the quality of patients' sensations. Overall, patients with obstructive disorders (asthma and chronic obstructive airways disease [COAD]) answered yes more often than those with restrictive or cardiac conditions, possibly reflecting differences in severity of disease. A cluster analysis separated the descriptors into 12 groups which appeared to describe different aspects of breathing discomfort. Relative to their response to other clusters, COAD patients were more inclined to identify distress, asthma patients to indicate wheeziness, restrictive patients to report rapid breathing, and the cardiac group to describe a need to sign. A second cluster analysis separated patients into 12 groups based on responses for the descriptor clusters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928957 TI - Ventilatory response to exercise after intracardiac repair of tetralogy of Fallot. AB - Previous radionuclide studies have shown residual maldistribution of lung perfusion after intracardiac repair of Tetralogy of Fallot (TF). Maldistribution of perfusion may also be detectable by measurements of gas exchange during exercise. Thus, we used exercise to test for maldistribution of perfusion in 13 children (8 to 18 yr of age) who were clinically well (New York Heart Association Class 1) 7 to 14 yr after repair of TF. Sixteen children, matched to the study group by age, size, and sex, served as control subjects. Peak oxygen consumption during progressive exercise on a cycle ergometer was 28.7 +/- 6.6 (SD) ml/kg/min for the study group compared with 35.7 +/- 6.9 for the control subjects (p less than 0.05). During steady-state exercise at a VCO2 of 0.6 L/min, ventilation (VE) and the ventilatory equivalents for oxygen (VE/VO2) and carbon dioxide (VE/VCO2) were high (VE/VCO2 = 35.9 +/- 4.4 versus 32.0 +/- 3.5, p less than 0.05), whereas mixed expired and end-tidal CO2 concentrations were low (PETCO2 = 34.0 +/- 2.4 versus 39.2 +/- 3.0 mm Hg, p less than 0.001). Indices of pulmonary function were normal; FVC values were 96 +/- 17% and FEV, values were 96 +/- 16% of predicted values. Therefore, children who are clinically well may exhibit gas exchange abnormalities compatible with mild maldistribution of lung perfusion 7 to 14 yr after repair of TF. PMID- 1928958 TI - Ventilatory drive and respiratory muscle function in pregnancy. AB - It has been demonstrated that during pregnancy expiratory reserve volume (ERV) decreases and minute ventilation (VE) increases initially and then stabilizes. In order to determine the role of thoracoabdominal mechanics, control of breathing, and inspiratory muscle function in these alterations, we studied inspiratory pressures, lung volumes, thoracic configuration, and respiratory drive in 18 normal pregnant women at Weeks 13, 21, 30, and 37 of pregnancy. Ten of them were studied 6 months after delivery. Transdiaphragmatic pressure (Pdi) was measured at Week 37 and 3 months after delivery in an additional group of seven women. VE as well as VT/TI increased early during gestation and remained unchanged thereafter. In contrast, mouth occlusion pressure (P0.1) increased progressively during pregnancy, from 1.53 +/- 0.16 (mean +/- SE) to 2.02 +/- 0.18 cm H2O, and fell significantly to 1.1 +/- 0.15 cm H2O after delivery, indicating that effective respiratory impedance increases during pregnancy. Mean P0.1 correlated with progesterone plasma levels (r = 0.918 p less than 0.05). No changes in Plmax, PEmax, and Pdimax, were observed. End-expiratory gastric pressure (Pga) increases significantly during pregnancy: 11.8 +/- 0.8 versus 8.4 +/- 1.12 cm H2O after delivery (p less than 0.012). This increment was correlated with the fall in ERV observed in late pregnancy (r = 0.74 p less than 0.05). Our results demonstrate that during pregnancy ventilatory drive and respiratory impedance increase with the consequent stabilization of VE, but our data do not permit us to differentiate whether the increment in P0.1 is secondary to the increase in impedance or to the rise in progesterone. Respiratory muscle function remains normal despite the alteration of thoracic configuration. PMID- 1928959 TI - Motor activity and apnea in preterm infants. Is there a causal relationship? AB - It is generally believed that all apneic episodes in preterm infants occur during sleep. Because occurrence of apnea during wakefulness has been documented in these infants, we investigated its frequency and characteristics in 10 premature infants using simultaneous polygraphic and video recordings. Behavioral arousal with motor activity preceded the onset of apnea in 202 episodes. Approximately 60% of episodes began within 15 s of arousal. Whereas most of the episodes were short and asymptomatic, hypoxia and/or bradycardia developed during 18 apneic spells, and these episodes accounted for a third of all apneic episodes that resulted in bradycardia or hypoxia in these infants studied. Essentially, all movement-related apneas (17 of 18) began within 15 s of arousal; motor activity continued throughout apnea in 13, whereas apnea resolved after cessation of motor activity in the remaining five. The main finding of the present study is that movement-related apnea is far more frequent than previously recognized. This finding is important in the clinical management of preterm infants with apnea. PMID- 1928960 TI - The effect of posture on upper airway dimensions in normal subjects and in patients with the sleep apnea/hypopnea syndrome. AB - The effect of posture on upper airway dimensions was assessed for two reasons. First, some patients with untreated sleep apnea/hypopnea syndrome (SAHS) report they sleep better sitting upright. Second, to allow comparison of the differing techniques used to determine the site of maximal airway narrowing in awake patients with SAHS, as some are carried out in the erect and others in the supine posture. Lateral cephalometry was therefore carried out in 33 nonsnoring normal subjects and in 29 patients with obstructive SAHS (mean apneas plus hypopneas, 46 per hour; range, 17 to 103). In both normal subjects and patients, uvular width was increased (p less than 0.05) in the supine posture, and this was associated with significant narrowing of the retropalatal airway in the patients with SAHS (erect, 5.0 +/- SD 2.6 mm; supine, 3.6 +/- 2.8 mm; p less than 0.01). In both normal subjects and patients, the retroglossal hypopharynx widened (p less than 0.05) in the supine posture (e.g., in patients with SAHS, posterior airway space was: erect, 11.5 +/- 4.5 mm; supine, 13.4 +/- 4.8 mm; p = 0.003). In the supine posture there was anterior movement of the hyoid and neck flexion in both groups. However, a study of the effect of neck flexion in the erect posture showed that neck flexion produced no changes in airway caliber. Thus, posture is an important determinant of upper airway dimensions. PMID- 1928961 TI - Bronchoscopy with bronchoalveolar lavage causes neutrophil recruitment to the lower respiratory tract. AB - Bronchoscopy with bronchoalveolar lavage (BAL) is a technique now widely utilized for both clinical and investigational purposes. At times, it is useful to perform bronchoscopy with BAL in a serial fashion. However, previous work in animals indicates that bronchoscopy with BAL can cause lower respiratory tract inflammation. To determine if BAL also causes lower respiratory tract inflammation in humans, sequential bronchoscopy with BAL was performed in 30 human subjects. Inflammation was evaluated using a quantitative visual assessment of bronchitis and by BAL. BAL was performed by instilling and aspirating five 20 ml aliquots of saline in each of three areas of the lung. The fluid returned from the first aliquot from each site was pooled as the bronchial fraction, and that from the remaining four aliquots was pooled as the alveolar fraction. Each volunteer was restudied at 2, 7, 24 or 72 h. Findings at the second bronchoscopy with BAL included an elevation in visual signs of large airways inflammation, which was greatest at 24 h. Bronchial neutrophils increased significantly, with the greatest effect seen at 7 h (5.3 +/- 2.0 versus 59.5 +/- 11.0%, SEM). The effect was most pronounced in the area of the lung previously lavaged, but was also seen in lobes that had not received BAL at the first bronchoscopy. Alveolar neutrophils also increased, with the maximal effect also seen at 7 h. Visible bronchial inflammation, bronchial neutrophils, and alveolar neutrophils returned to the normal range by 72 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928962 TI - Bronchoalveolar mast cells in normal farmers and subjects with farmer's lung. Diagnostic, prognostic, and physiologic significance. AB - To evaluate the specificity and significance of increased lavage mast cells in farmer's lung, we examined the lavage cell differentials of 89 farmers and 19 normal nonfarming control subjects. The farmers were divided into four groups: acute farmer's lung (n = 17), farmers with one or more prior episodes of farmer's lung who remained in daily contact with hay (n = 26) or quit farming (n = 14), and normal farmers (n = 36). A total of 14 of the subjects with prior episodes of farmer's lung and still farming and 15 normal farmers were evaluated twice at a 2 yr interval. The lavage mast cell numbers were significantly higher in acute farmer's lung (7.5 +/- 7.3 x 10(3)/ml, mean +/- SD) and ex-farmer's lung who were still farming (1.2 +/- 1.3 x 10(3)/ml) than in normal farmers (0.1 +/- 0.1 x 10(3)/ml) (p less than 0.01). A total of 8 of 14 exfarmer's lung patients who had quit farming and 18 of 36 normal farmers had an increased number of mast cells in lavage, but mast cell count never exceeded 0.5% of total recovered cells. In the acute farmer's lung and ex-farmer's lung-still farming groups, the mast cell count correlated with the lymphocyte count: r = 0.83 and r = 0.69 (p less than 0.001), respectively. In the two groups evaluated twice, mast cell numbers at the first study did not correlate with changes seen at the second study in chest roentgenogram and pulmonary functions. We conclude that an increase in lavage mast cells occurs commonly as a part of the immune response against thermophilic bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928963 TI - Antigen-induced proliferative response of lavage and blood T lymphocytes. Comparison of cells from normal subjects and patients with sarcoidosis. AB - To evaluate the mechanisms responsible for anergy in sarcoid patients, we studied the ability of highly purified lavage and blood T lymphocytes from control subjects and patients with sarcoidosis to proliferate in response to recall antigens, and compared the results of antigen-induced lymphocyte proliferation with the clinical characteristics of the patients. Both blood and lavage T lymphocytes from all control subjects proliferated in response to purified protein derivative (PPD) and candida antigens, and no significant difference was observed comparing the proliferation of lymphocytes from the two sources. The antigen-induced proliferation of blood and lavage T lymphocytes from sarcoid patients was reduced compared with that of the corresponding cell populations from normal subjects (p less than 0.01 for PPD, Candida, and tetanus), and the proliferative response of sarcoid lavage lymphocytes was significantly lower than that of blood T lymphocytes from these patients. No evidence for inhibition of T lymphocyte proliferation by accessory cells (blood monocytes) or CD8+ T lymphocytes was observed, and the refractory state could not be overcome by adding exogenous recombinant human IL-2 or IL-4. An inverse correlation was observed between the PPD-induced proliferation of sarcoid lavage T lymphocytes and criteria associated with "active" disease, including lymphocytes/ml lavage fluid (p less than 0.003), 67Ga uptake (p less than 0.005), and serum angiotensin converting enzyme activity (p less than 0.005). Lavage lymphocytes from patients studied early in the course of the disease proliferated better than those from patients with more long-standing disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928964 TI - Lung peptidases, including carboxypeptidase, modulate airway reactivity to intravenous bradykinin. AB - We investigated the effect of inhibition of carboxypeptidase, neutral endopeptidase, or angiotensin converting enzyme on airway reactivity to intravenous bradykinin in guinea pigs. Bradykinin reactivity in intact, unanesthetized, spontaneously breathing animals was determined by measuring specific airway resistance in response to increasing doses of intravenous bradykinin or acetylcholine. We found that phosphoramidon and/or captopril (specific antagonists of neutral endopeptidase and angiotensin converting enzyme, respectively) increased airway reactivity to bradykinin, but the combination had no effect on muscarinic reactivity. Although 2-mercaptomethyl-3 guanidinoethylthiopropanoic acid (MGTA, a carboxypeptidase inhibitor) alone did not alter bradykinin reactivity, MGTA in the presence of both phosphoramidon and captopril significantly potentiated bradykinin-induced airway reactivity. In comparison, this did not affect reactivity to acetylcholine. Having found that carboxypeptidase inhibition could augment kinin-induced airway reactivity, we subsequently assayed for and identified carboxypeptidase M activity in guinea pig lung. We found considerable carboxypeptidase M activity in guinea pig lung subcellular fractions, the 100,000 x g membrane pellet having the highest specific activity. Our data indicate that airway reactivity to intravenous bradykinin is modulated by the activity of endogenous neutral endopeptidase, angiotensin converting enzyme, and carboxypeptidase, all of which are present in lung cell membranes. This study also suggests that the influence of carboxypeptidase per se may be substantially enhanced if endogenous pulmonary neutral endopeptidase and angiotensin converting enzyme activities are reduced. PMID- 1928965 TI - Biologic characterization of ICI 200,880 and ICI 200,355, novel inhibitors of human neutrophil elastase. AB - ICI 200,880 and its close structural analog, ICI 200,355, are representatives of a new chemical class of inhibitors of human neutrophil elastase (HNE). Both compounds are substituted tripeptide ketones, which demonstrated competitive kinetics versus HNE, with identical Ki values of 5.0 x 10(-10) M. The selectivity of ICI 200,880 for HNE versus a variety of enzymes ranged from 150-fold [relative to porcine pancreatic elastase (PPE)] to greater than 360,000-fold in favor of HNE. The compound effectively inhibited HNE-hydrolysis of bovine ligamentum nuchae elastin. In pharmacokinetic studies, ICI 200,880 and ICI 200,355 displayed long retention times when administered directly to the lung and were rapidly eliminated after intravenous administration. Pretreatment of hamsters with either inhibitor before intratracheal administration of HNE produced dose- and time dependent inhibition of enzyme-induced increases in lung weight, total lavageable red cells, and total lavageable white cells. Aerosol administration of ICI 200,880 produced similar results. Subcutaneous administration of either 50 or 100 mumol/kg (twice/day) of ICI 200,880 for 14 or 28 days prevented the time dependent increase in alveolar diameter produced by a single intratracheal dose of PPE when compound dosing was initiated 24 h after the enzyme. Treatment of hamsters with the same protocol and doses of ICI 200,880 for 8 wk prevented the destructive lesion induced by a single intratracheal dose of HNE. It is concluded that ICI 200,880 and ICI 200,355 have biochemical, pharmacokinetic, and pharmacologic profiles that make them useful therapeutic agents for understanding the role of HNE in various diseases. ICI 200,880 is presently being evaluated in humans. PMID- 1928966 TI - Effects of K+ channel blockers on vascular tone in the perfused rat lung. AB - To learn more of the role of K+ channel activity in the regulation of pulmonary vascular tone, we compared the pressor effects of the differential blockers of numerous K+ channels, tetraethylammonium chloride and 4-aminopyridine, and the inhibitor of ATP-sensitive K+ channels glibenclamide in meclofenamate-treated salt solution-perfused rat lungs. Tetraethylammonium (1 to 20 mM) and 4 aminopyridine (1 to 10 mM), but not glibenclamide (1 to 20 microM) caused vasoconstriction in the normoxic lung. The Ca++ channel blocker nifedipine (0.1 microM) and the alpha adrenoceptor antagonist phentolamine (10 microM) inhibited the 4-aminopyridine response by about 50% and reduced slightly the smaller tetraethylammonium response. 4-Aminopyridine and, to a lesser extent, tetraethylammonium, but not glibenclamide, also potentiated peak vasoconstriction to angiotensin II and airway hypoxia. Nifedipine, but not phentolamine, inhibited hypoxic vasoconstriction and prevented the potentiation by 4-aminopyridine. These results suggest that Ca(++)- and/or voltage-activated (not ATP-sensitive) K+ channels may be important in maintaining low pulmonary vascular tone. PMID- 1928967 TI - Alveolar attachments in emphysema of human lungs. AB - We have studied alveolar attachments to membranous bronchioles in 41 patients enrolled in the National Institutes of Health Intermittent Positive Pressure Breathing Trial who died, came to autopsy, and provided adequate tissue for examination. The patients had moderate to severe chronic airflow obstruction and, on the average, severe emphysema. We measured the number of normal attachments per membranous bronchiole per case (N), the number of normal attachments per mm of circumference per bronchiole per case (Nunit), and the ratio of abnormal to all attachments (R). All measurements correlated closely to all measurements of emphysema and to irregular shape of bronchioles (deformity index). Measurement of abnormal attachments correlated with abnormal tests of pulmonary function, including evidence of airflow obstruction and diffusing capacity for carbon monoxide (DLCO). Nunit showed the most frequent correlations, but both N and Nunit were only related independently of emphysema for Phase III of the single breath nitrogen test. R was related to loss of DLCO. We conclude that loss of attachments is not itself a cause of airflow obstruction but rather a correlate of emphysema, which is the proximate cause of the obstruction. Loss of alveolar attachments has an effect only on the single-breath nitrogen tests independent of emphysema. PMID- 1928968 TI - Scanning electron microscopic observations of emphysema in humans. A descriptive study. AB - We have performed dissecting light and scanning electron microscopy (SEM) on 14 lungs with mild centrilobular emphysema, two of which also had mild panacinar emphysema. The lungs were surgically resected, mainly for cancer. The walls of centrilobular emphysema were either thick or thin. The former were less common and represented fibrosis of the walls. The latter were less fibrotic, but some fibrosis was seen. Adjacent alveoli were compressed and distorted, and overlapping walls of air spaces occurred. In panacinar emphysema alveolar ducts were enlarged and flattened with transverse linear bands interpreted as flattened walls of enlarged alveoli. The walls of air spaces were chiefly lined by type I and type II epithelial cells, but occasionally bronchiolar epithelium lined the proximal emphysematous spaces. Supplying bronchioles showed diminished numbers of ciliated cells with cilia of reduced height. SEM was much more sensitive than dissecting microscopy in recognizing emphysema. The apparent fibrosis suggests that the definition of emphysema may have to be reconsidered and that if fibrosis is apparent, the proteolysis-antiproteolysis hypothesis of the pathogenesis of emphysema may have to be modified. PMID- 1928969 TI - Pulmonary surfactant as a vehicle for intratracheal delivery of technetium sulfur colloid and pentamidine in hamster lungs. AB - Tracheal instillation of pentamidine in a surfactant vehicle may be an effective direct method of antibiotic delivery to the lungs. In 10 healthy hamsters, we compared the pulmonary distribution of 99mTc sulfur colloid (TcSC) mixed with pentamidine, using as a vehicle either surfactant (n = 5) or saline (n = 5). Each animal was instilled with 0.25 ml/kg of suspension containing 0.0018 mCi TcSC and pentamidine mixed with either surfactant or saline. After 4 h of spontaneous respiration, the lungs were excised, inflated to TLC, dried, and sliced into 3-mm cross sections from apex to base. Autoradiographs were examined to evaluate 99mTc distribution. The surfactant group had detectable radioactivity in 93% of all slices compared with 72% in the saline group (p = 0.02). Six slices per animal (43% of total) and their corresponding autoradiographs were analyzed for distribution of radioactivity. Lung slice area was determined by planimetry, and autoradiograph area was determined by video densitometry. We calculated the fraction of each lung slice with detectable radioactivity. The surfactant group had 41% of the lung slice areas exposed compared with 21% in the saline group (p = 0.02). The coefficient of variation of radioactive intensities within each slice was used as an index of spatial uniformity. There was a trend towards more uniform distribution in the surfactant group, with a narrower range of variation of intensities (1.51 to 2.56) than the saline group (1.95 to 6.47). We conclude that a surfactant vehicle significantly increases airspace deposition of TcSC and pentamidine instilled intratracheally in normal hamster lungs, and may improve uniformity of spread. PMID- 1928970 TI - Pectus excavatum and scoliosis. Thoracic anomalies associated with pulmonary disease caused by Mycobacterium avium complex. AB - We studied the frequency of pectus excavatum or otherwise abnormally narrowed anterior-posterior thoracic dimension and of thoracic scoliosis among consecutive series of 67 patients with pulmonary disease due to Mycobacterium avium complex and 55 patients with pulmonary Mycobacterium tuberculosis. Among those with M. avium, pectus excavatum and abnormal narrowing was present in 27% and scoliosis was seen in 52%; overall, 47 of the 67 (70%) had one or both of these anomalies. By comparison, of those with M. tuberculosis only 5% had pectus excavatum or abnormal narrowing, only 13% had scoliosis; and none had both. The prevalence of pectus excavatum and abnormal narrowing among female M. avium complex patients was significantly greater than among female tuberculosis patients (p = 0.05) or in the general population (p less than 0.001). Among male M. avium complex patients, pectus excavatum and abnormal narrowing was significantly more common than in the general population (p less than 0.001) but not significantly different than among male tuberculosis patients (p = 0.264). For all M. avium complex versus all M. tuberculosis patients the prevalence of pectus excavatum abnormal narrowing was significantly greater (p = 0.013). Scoliosis was significantly more common among all M. avium complex patients than among M. tuberculosis patients or the general population. We believe that these anomalies, which are associated with a variety of heritable connective disorders, are phenotypic markers of patients who are at increased risk for pulmonary disease due to environmental mycobacteria, such as M. avium complex. PMID- 1928971 TI - Mode of presentation and diagnosis of bacterial pneumonia in human immunodeficiency virus-infected patients. AB - Bacterial pneumonia (BP) has recently been reported to be more frequent in human immunodeficiency virus (HIV)-infected patients than in normal hosts. This study reviews the clinical and radiologic manifestations of BP in 132 consecutive pulmonary episodes over a 15-month period. BP was defined on a clinical basis as a pulmonary infiltrate accompanied by fever and improving in a few days with conventional antibiotics (trimethoprim-sulfamethoxazole excluded). In patients undergoing bronchoscopy (97 procedures), semiquantitative cultures and cell differentials of bronchoalveolar lavage (BAL) were performed, in addition to conventional staining and cultures for opportunistic infections. BP were frequent (45%), and the usual community-acquired pathogens were found. The radiologic manifestations of BP were often unusual, however, and 47% were indistinguishable from the typical appearance of Pneumocystis carinii pneumonia. BAL cultures had a sensitivity of 83 or 23%, depending on whether antibiotics were administered before bronchoscopy, using a cutoff value of greater than or equal to 10(4) bacteria/ml. The specificity of BAL culture was of 80.5% if patients with P. carinii pneumonia were taken as a control group. We conclude that BP is frequently encountered in HIV-infected patients. The clinical and radiologic presentation of BP may be indistinguishable from that of opportunistic infections. Semiquantitative cultures of BAL appear a valuable diagnostic tool to avoid unnecessary invasive diagnostic procedures or treatments. PMID- 1928972 TI - Magnetic resonance imaging of the upper airway in obstructive sleep apnea before and after chronic nasal continuous positive airway pressure therapy. AB - Magnetic resonance imaging (MRI) provides high-resolution images of the upper airway and is useful for assessing conditions associated with increased tissue water content. To determine whether nasal continuous positive airway pressure (CPAP) changes awake upper airway morphology in obstructive sleep apnea (OSA), we performed awake upper airway MRI scans on five male patients with moderate to severe OSA before and after 4 to 6 wk of nasal CPAP therapy. MRI scans were performed using spin echo pulse sequences to examine detailed anatomy and inversion recovery sequences to assess mucosal water content. Patients did not have nasal CPAP applied during the MRI scans. Axial and sagittal images were obtained, and tracings were made of the upper airway, tongue, and soft palate. Utilizing computer graphics, cross-sectional areas and volumes were calculated for each anatomic structure. A subjective grading system was used to assess upper airway mucosal water content. Pharyngeal volume and minimum pharyngeal cross sectional area increased (p less than 0.05) and tongue volume decreased (p less than 0.01) following chronic nasal CPAP therapy. The increase in pharyngeal volume occurred mainly in the oropharynx (p less than 0.01). Upper airway mucosal water content decreased in the oropharynx (p less than 0.05). We conclude that chronic nasal CPAP therapy during sleep in patients with OSA produces changes in awake upper airway morphology. These changes may be due to resolution of upper airway edema. The upper airway of patients with OSA can be accurately and repeatedly assessed using MRI. PMID- 1928973 TI - Airway obstruction and bronchial hyperresponsiveness in left ventricular failure and mitral stenosis. AB - Small and large airways narrow in LVF and the term cardiac asthma is often used. However, current usage of this term is inconsistent and its meaning is therefore ambiguous. The term is better avoided despite several emerging similarities with bronchial asthma. Airway narrowing may be precipitated by acute elevation of pulmonary or bronchial vascular pressures. This appears to be mainly due to reflex bronchoconstriction. The afferents of this reflex are C-fibers with their endings in the lung parenchyma, bronchi, and pulmonary blood vessels and RAR in the larger airways, and they run in the vagus nerves, as do the efferent bronchoconstrictor fibers. Chronic elevation of pulmonary vascular pressures, as in mitral stenosis, are also associated with airway narrowing. Pulmonary edema (in the absence of vascular hypertension) also causes reflex bronchoconstriction. Bronchial responsiveness to bronchoconstrictor drugs is increased in LVF, partly, at least, due to reflex mechanisms. Bronchial mucosal swelling may also contribute. Narrowing by nonreflex mechanisms definitely occurs and there is direct evidence that decreased lung volume caused by pulmonary edema may cause this. There is little evidence for bronchial narrowing due to the mechanical effect of peribronchial edema, or by swelling of the bronchial mucosa. However, edema foam may terminally cause grave obstruction. Patients with LVF are commonly treated with bronchodilator drugs, but the basis for this approach needs further clarification. PMID- 1928974 TI - The potent and selective sulfidopeptide leukotriene antagonist, SK&F 104353, inhibits aspirin-induced asthma. AB - We have determined the effect of prior inhalation of the LTD4 antagonist SK&F 104353 on the response to aspirin ingestion in six aspirin-sensitive asthmatic subjects (five women and one man 31 to 54 yr of age) in a randomized, double blind, cross-over, placebo-controlled study. Pretreatment with inhaled SK&F 104353 (average nebulized dose, 893 micrograms) inhibited the response by a mean of 47% (p = 0.02). The inhibition was partial, ranging from 43 to 74% in five subjects. In the remaining subject, there was no effect of the drug on the asthmatic response. We conclude that the mechanism of aspirin-induced asthma is at least partially mediated by the leukotrienes in the majority of susceptible patients and that leukotriene antagonists may be useful in the treatment of aspirin-induced asthma. PMID- 1928975 TI - Clinical usefulness of n-of-1 randomized controlled trials in patients with nonreversible chronic airflow limitation. AB - To determine if n-of-1 randomized controlled trials (n-of-1 RCT) are useful in the care of patients with nonreversible chronic airflow limitation (CAL). Individual trials had a double-blind, randomized, multiple crossover design. Patients with CAL were recruited from several respirology practices. For each individual trial the main outcome measure was a symptom questionnaire; peak flow measurements were used as a secondary measure. Physicians' plans of management (before and after trials) and confidence in the plans were determined. The proportion of trials that provided a definite clinical or statistical answer was established. Patients were followed, and long-term adherence to decisions based on n-of-1 RCT was examined. A total of 26 n-of-1 RCT in patients with CAL were attempted; 18 of these (69%) were completed. After 17 (94%) of the completed trials clinicians expressed a high degree of confidence in their management plans, confidence that was not, in any case, present before the trial. After 8 n of-1 RCT (44% of all completed, or 31% of all trials) clinicians decided to stop the drug, which would otherwise have been continued indefinitely. In all 17 of the clinically definite n-of-1 RCT, the management decision that followed the trial was still being adhered to 40 months (on average) after completion of the trial. The results support the feasibility and usefulness of n-of-1 RCT in respirology practice. PMID- 1928976 TI - Animals in medical research. Official statement of the American Thoracic Society. PMID- 1928977 TI - Estimating left ventricular filling pressure in patients receiving positive end expiratory pressure. PMID- 1928978 TI - Prevention of central venous catheter sepsis: a prospective randomized trial. AB - A prospective randomized trial was undertaken to evaluate the influence of routine 72-hour catheter exchange and the use of an implantable collagen cuff in preventing central venous catheter infection in critically ill patients requiring multiple lumen central venous access. Patients were randomized to one of four groups, which determined whether the central venous catheter placed would be removed at 3 or 7 days and whether an implantable collagen cuff would be used or not. Upon removal, cultures of the central line tip, the insertion site, and peripheral blood were obtained. One hundred and fifty-nine catheters were studied in 85 patients during a 14-month period. There were 26 (16.4%) episodes of catheter colonization and four (2.5%) episodes of catheter infection in the entire population. Catheter colonization rates (same organisms cultured from catheter tip and skin site) were 14.5 per cent at 3 days and 18.4 per cent at 7 days. Infection rates (same organism cultured from catheter tip and peripheral blood culture) were 2.4 per cent at 3 days and 2.6 per cent at 7 days. With regard to the use of the collagen cuff, colonization rates were 14.5 per cent with the use of the cuff and 18.1 per cent without the use of the cuff. Infection rates were 5.3 per cent with the use of the cuff and 0 per cent without the use of the cuff. None of these differences reached statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928979 TI - A safe approach to the treatment of iliac artery aneurysms. Aortobifemoral bypass grafting with exclusion of the aneurysm. AB - Aneurysms of the iliac arterial system are often difficult to approach surgically. Aortobifemoral (ABF) bypass grafting with exclusion of the aneurysms can be used as an alternative to the usually recommended approach of endoaneurysmorrhaphy. Fourteen patients with iliac artery aneurysms treated by ABF are compared to 16 patients treated by direct repair to compare the incidence of complications related to decreased pelvic blood flow or to the presence of the excluded iliac artery aneurysm. There were no differences between the two groups. Therefore, it is concluded that ABF is a reasonable alternative in the treatment of iliac artery aneurysms. PMID- 1928980 TI - Carotid endarterectomy in a community hospital surgical practice. AB - Three hundred twenty-four carotid endarterectomies (CEAs) were performed on 303 patients over 5 years. Sixty per cent of the patients were symptomatic with completed stroke (36.4%), amaurosis fugax (35.4%) or transient ischemic attack (TIA) (50.5%). Some patients had multiple symptoms. Perioperative stroke occurred in four patients (1.2%) and 30-day mortality in five (1.5%). The combined stroke mortality rate was 2.8 per cent. Other postoperative complications included TIA (1.9%), cranial nerve injury (3.1%), wound hematoma (6.5%), and hypertensive reperfusion syndrome (9.6%). Ten early reoperations were performed for wound hematoma (7) or technical problems (3). Follow-up of 284 CEAs (88%) at a means of 31 months revealed 33 late deaths, with two due to stroke. Late strokes occurred in 11 patients (3.9%). Five late strokes were ipsilateral (1.8%) and six were contralateral (2.1%) to the operated carotid artery. Ninety-seven carotid arteries were evaluated by duplex ultrasound scanning at a mean postoperative interval of 27.2 months. Ninety-two per cent had 0-30 per cent restenosis, 5 per cent had 40 per cent to 60 per cent restenosis and 3 per cent had 70 per cent or greater restenosis. The authors conclude that CEA can be performed with acceptable morbidity and mortality rates and that it is a durable operation that reduces the risk of late stroke. PMID- 1928981 TI - Repair of large paraesophageal hernia with complete intrathoracic stomach. AB - Paraesophageal hiatal hernia accounts for only five per cent of all diaphragmatic defects but is a potentially dangerous lesion. Herniation of the entire stomach, at times accompanied by the omentum, transverse colon, and small bowel, may occur in some patients, and incarceration and strangulation may be the result. Three patients underwent repair of large paraesophageal hernias, in one instance as an emergency. Symptoms of pain, bloating, and occasional regurgitation had been present for 17, 30, and 40 years. The operations included repair of the hiatal defect, anterior gastropexy, and Nissen fundoplication in two patients. In the third patient, a pyloromyotomy was performed as well. A subsequent thoracotomy was necessary in one patient to excise a persistent large hernia sac, which was densely adherent to the lung and mediastinal structures. All patients were asymptomatic after periods of 9 months, 1 year, and 7 years. The unique anatomic and clinical features of large paraesophageal hernias containing intrathoracic abdominal viscera, as well as the technique of operative repair, are presented. PMID- 1928982 TI - The management of acute cholecystitis in elderly patients. AB - Acute cholecystitis is a common cause of emergency room admissions in elderly patients, and may have an atypical course with serious complications and high mortality. The authors present 131 elderly patients (aged 70 and older) who were treated for acute cholecystitis. The most common complaint was right upper abdominal pain (73%), followed by fever (55%), vomiting (48%), palpable mass (22%) and jaundice (13%). Twelve per cent of the patients were in septic shock on admission. Most patients (74%) had severe concomitant disease, increasing their operative risk significantly. Patients were prepared for surgery by hydration, nasogastric drainage, and antibiotics, while imaging was performed. They were all operated on within 48 hours. The operation of choice was cholecystectomy, which was performed in 86 patients. In 45 older and high risk patients, cholecystostomy was performed. The decision to perform cholecystostomy was taken prior to the operation, and was based on the estimated operative risk. Five patients (3.8%) died postoperatively. The major cause of death was cardiovascular disorders. Major complications occurred in 14.5 per cent and minor in 23 per cent of the patients. The complication rate correlated with severe concomitant diseases and older age groups. Patients with fever and leukocytosis had a better outcome, possibly reflecting a better immunologic status. The authors conclude that aggressive preoperative preparation and judicious use of cholecystostomy as a life-saving drainage procedure can lower the mortality from acute cholecystitis in the elderly population. PMID- 1928983 TI - Patterns of liver test abnormalities in patients with surgical sepsis. AB - The progression of changes in biochemical liver test results during moderate and severe sepsis (SS) was studied prospectively in 43 patients admitted to a surgical intensive care unit. Using predetermined criteria, severity of sepsis was assessed by physicians blinded to the liver test results. Linear regression analysis showed that bilirubin levels increased at a rate approximating 0.95 mg/dl/day in patients with SS, whereas alkaline phosphatase levels did not rise initially in these patients. Following peak hyperbilirubinemia, however, alkaline phosphatase levels increased at approximately 4 IU/L/day. In patients with moderate sepsis (MS), bilirubin levels increased slowly (approximately 0.4 mg/dl/day) but alkaline phosphatase levels increased rapidly (approximately 29 IU/L/day). Following peak hyperbilirubinemia, alkaline phosphatase levels did not change. These data define patterns of liver test abnormalities of clinical importance. Rapidly rising bilirubin levels with little change in alkaline phosphatase levels are associated with SS, whereas markedly elevated alkaline phosphatase levels may indicate MS or resolution of SS. In critically ill surgical patients subjected to many potential hepatic insults, recognition of liver dysfunction with these patterns should alert the clinician to the possibility of underlying sepsis. PMID- 1928984 TI - Surgical complications of pica: report of a case of intestinal obstruction and a review of the literature. AB - The authors describe a patient with chronic renal failure who developed intestinal obstruction from talcum powder pica. A literature review found 43 previously reported cases of surgical complications caused by various forms of pica. Most occurred in women, blacks, aborigines, children, or the mentally retarded--all groups in whom pica occurs more frequently than the general population. Intestinal obstruction was the most common clinical presentation and the ileum most often the site of obstruction reported at surgery. Perforation with peritonitis was the next most common presentation but three cases of colon perforation were diagnosed only at surgery or postmortem. Mixed pica (paper, plastic bags, cloth, string) seemed more likely to require surgery and to cause perforation. An accurate preoperative diagnosis was made most often when a history of pica was sought, and opacity on abdominal X rays correctly interpreted. These clues to pica as the underlying cause of abdominal complaints should not be neglected in patients who are members of the groups known to be at higher risk of this compulsive eating disorders. PMID- 1928985 TI - Detection of preoperatively unrecognized multiple pancreatic pseudocysts by intraoperative ultrasonography. Report of two cases. AB - During two pancreatic operations, intraoperative ultrasonography detected multiple pancreatic pseudocysts that were unrecognized preoperatively. In each operation, a single pseudocyst was detected by preoperative ultrasonography, computed tomography, and intraoperative surgical exploration. In addition, high resolution ultrasonography used during the operations also identified and precisely localized additional smaller pseudocysts. Also, the use of color Doppler imaging during the operations enabled the delineation of small blood vessels around the pseudocysts. The accurate diagnosis of multiple pseudocysts and the precise anatomic information provided by intraoperative ultrasonography permitted appropriate surgical treatment of the pancreatic pseudocysts which, in turn, might help prevent recurrence of the disease. PMID- 1928986 TI - Radionuclide cholescintigraphy in patients with suspected biliary tract obstruction. AB - Radionuclide cholescintigraphy is used to help establish the diagnosis of acute cholecystitis and is thought to provide additional information regarding the patency of the biliary duct system. Nonvisualization of the extrahepatic biliary duct system and lack of excretion into the duodenum despite uptake in the liver (a positive study) is considered indicative of common bile duct obstruction. The authors retrospectively reviewed 281 hepatobiliary cholescintigrams done at Stamford Hospital from July 1, 1987 to June 30, 1989. Previous authors have demonstrated a false-positive rate of eight to 15 per cent in those cases that have a documented normal extrahepatic biliary system at operation. Of those patients explored after a common bile duct obstruction pattern depicted by cholescintigram in the authors' series, 46 per cent of patients were found to have normal extrahepatic biliary systems. Factors possibly contributing to this high false-positive rate are discussed. The utility of radionuclide hepatobiliary scans may be limited for diagnosis of biliary duct obstruction. PMID- 1928987 TI - Obstructing leiomyoma of the common hepatic duct bifurcation simulating a Klatskin tumor. AB - The first reported case of a leiomyoma of the proximal bile duct simulating a Klatskin tumor and causing obstructive cholestasis is presented. Diagnosis was made at the time of exploratory surgery. Surgical management included complete excision with Roux-en-Y hepatic-ojejunostomy. PMID- 1928988 TI - Quality assurance and medical stupidity. PMID- 1928989 TI - Open breast biopsy. A critical analysis. AB - A retrospective study of open breast biopsies performed from January 1, 1988 to December 31, 1988 was undertaken to compare the malignancy rate of the authors with that generally reported in the literature. This was done to determine if biopsy of mammographically demonstrated nonpalpable lesions had a favorable impact on outcome, and to identify factors with high relative risk or predictive value for malignancy. Office records of 518 patients who underwent breast biopsies were reviewed, 122 of which (23.6%) proved to be malignant. The malignancy rate for needle localized excisions of nonpalpable lesions was 17.5 per cent. Of these, 28 per cent were stage tumor in situ (TIS), 60 per cent stage 1, and 12 per cent stage 2. A higher percentage of palpable lesions were malignant than were nonpalpable lesions (29.0%). Of the palpable malignancies, 28 per cent were stage 1, 51 per cent stage 2, 13 per cent stage 3, and 8 per cent stage 4. Those who were older than 40 years of age yielded a significantly higher malignancy rate when compared with the less than 40 age group (28.6% versus 6.7%, P less than 0.001). Lesions that appeared on mammogram as nodules, calcium, or both had a higher malignancy rate than those where no lesion was identified (25.3% versus 14.2%, P less than 0.001). None of these factors alone or in combination ruled out malignancy. Biopsy of nonpalpable mammographically demonstrated lesions lead to detection of breast cancer at an earlier stage. Age greater than forty years, demonstrable lesion by mammogram, and palpable lesion were significant predictors of malignancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928990 TI - Elimination of urinary retention following inguinal herniorrhaphy. AB - In a group of 880 patients undergoing inguinal herniorrhaphy using local anesthesia, the incidence of postoperative urinary retention was 0.2 per cent. During the same period, a similar group of 200 patients had their hernias repaired using general or spinal anesthesia. The incidence of postoperative urinary retention was 13 per cent. The authors contend that the use of local anesthesia in inguinal hernia repair almost eliminates postoperative urinary retention. PMID- 1928991 TI - Pancreatic cancer in Illinois. A report by 88 hospitals on 2,401 patients diagnosed 1978-84. AB - A retrospective study of survival results for pancreatic cancer was performed. The study had two objectives: 1) to relate the extent of disease and management to survival, and 2) to determine whether newer treatment combinations have altered prognosis. Cancer registrars from 88 Illinois hospitals reviewed original medical records and submitted standardized report forms on 2,401 patients diagnosed between 1978-84. Three-year survival time was longer after laparotomy/bypass plus radiation/chemotherapy than for laparotomy/bypass alone (P less than .02). But the difference in survival between resection versus resection, radiation, and chemotherapy was not significant (P = .16). After resection, the median survival for 78 Stage I patients was 12.5 months, whereas for 181 Stage I patients after laparotomy/bypass it was 6.8 months (P less than .00001). For patients without metastases, 3-year survival was significantly better for 249 patients in whom cancer was resected versus 568 unresected patients (P less than .001). Survival was longer for 568 unresected patients without gross metastases than for 954 patients with metastatic disease found at laparotomy (P less than .05). From this study the authors concluded that: 1) since 3-year survival results were higher than expected after resection for localized cancers, resection is still desirable when it can be done with acceptable complication risks, and 2) the use of multiple treatment modalities for pancreatic cancer warrants further study in organized trials. PMID- 1928992 TI - Adrenocortical carcinoma. AB - Ten patients, seven women and three men, ages 47 to 76 years (mean 58.6 years), treated for adrenal cortical carcinoma between 1971 and 1989, were reviewed. Three (30%) of the tumors were nonfunctioning. The remaining seven (70%) were functioning, six of them occurring in women. Common presenting features were hormonal excess, distant metastases, weight loss, and abdominal pain. The primary tumor was resected in all patients, only two of whom had disease confined to the adrenal gland. Tumor diameter ranged from 9 to 21 cm (mean 15.7 cm). Inferior vena caval or right atrial extension of tumor thrombus was present in two patients. Excluding two deaths from postoperative complications, seven patients died of their disease after a mean survival of 25 months (range 2 to 84 months). Of seven patients who received o,p'-DDD treatment for metastatic or recurrent tumor, three (43%) had an objective response. In two patients, tumor regression was complete and was associated with prolonged survival. The first patient underwent resection of recurrent tumor on two occasions in addition to receiving o,p'-DDD and survived 84 months. The second patient had complete regression of pulmonary and liver metastases confirmed at laparotomy and thoracotomy and remains free of disease at 78 months. None of the five patients treated with various combinations of cytotoxic chemotherapy had an observable response, and no measurable effect was seen in a single patient following abdominal radiotherapy. It is concluded that resection for local recurrence may prolong survival and that significant and lasting tumor regression is possible with o,p'-DDD administration. Beneficial results from cytotoxic agents, however, could not be demonstrated. PMID- 1928993 TI - Risk factors for immediate prosthetic postmastectomy reconstruction. AB - The charts of 44 women who underwent 47 immediate postmastectomy prosthetic breast reconstructions (IPMPBR) with subpectoral prostheses (long-term implant, long-term expandable implant or tissue expanders followed by long-term prosthetic placement) were retrospectively reviewed. Follow-up was from 3 to 49 months (median 18 months). Patient ages ranged from 31 to 77 years (median 42) but 82 per cent were under 60 years old. Indications for mastectomy were infiltrating cancer in 30 patients, intraductal cancer in 11, lobular carcinoma in situ in two and prophylaxis in one. There were 11 patients with pathologic Stage I, 15 with Stage II, three with Stage III and one with Stage IV breast cancer. Adjuvant chemotherapy (CTX) was given to 17 women, adjuvant hormonal treatment to nine, and radiation therapy (RT) to five. One patient had prosthesis extrusion and removal. Two patients had late periprosthetic infections (PPI) with consequent prosthesis removal. CTX did not have a significant association with PPI (two of 14 with CTX vs 0 of 29 without, P = 0.1). However, fill port migrations, prosthesis deflations, and greater than 1 complication were significantly associated with these infections (two of three vs 0 of 38, P = 0.004; two of two vs 0 of 45, P = 0.001; two of four vs 0 of 43, P = 0.006). Skin flap cellulitis and postoperative seroma were also associated with PPI (P less than 0.003 and less than 0.006, respectively). These factors were all also significantly associated with involuntary prosthesis loss (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928994 TI - Spinal anesthesia reduces the hazard of apnea in high-risk infants. AB - General anesthesia in premature babies is associated with a significant risk of life-threatening apnea. Spinal anesthesia in the high-risk infant is simple, safe, and effective, but the incidence of apnea with its use has not been previously determined. The total absence of apnea in 84 high-risk infants suggests that surgery below the umbilicus under spinal anesthesia can safely be performed on an outpatient basis in preterm infants or babies with a history of apnea. Ketamine as an adjunctive agent adds no apparent risk. The technique is relatively easy, surgery is not compromised, and parental acceptance is high. PMID- 1928995 TI - Morbidity and mortality following total abdominal colectomy for massive lower gastrointestinal bleeding. AB - During the period of 1980 to 1986, 49 total abdominal colectomies were performed at the authors' institution for lower gastrointestinal bleeding. The overall mortality was 13 of 49 (27%). In the elective/urgent group, mortality was one of 14 (7%); in the emergency with ileostomy group it was two of two (100%); and in the emergency with anastomosis group it was ten of 33 (30%). Morbidity and mortality in this latter group were affected by age [mortality three of 15 (21%) for age less than 70 vs seven of 18 (37%) for age greater than or equal to 70] and the number of units of blood needed preoperatively and intraoperatively. There was no effect on outcome from type of anastomosis (stapled vs hand-sewn), choice of antibiotics, degree of underlying illness, or day of operation following admission. Thirteen patients had less than 10 units of blood transfused; one (7%) died and there was one complication. Conversely, 20 patients had ten or more blood transfusions and nine (45%) died (P = 0.05 vs former group). This latter group also had 16 major complications, including five anastomotic leaks, three intra-abdominal abscesses, and three myocardial infarctions. Total abdominal colectomy when done as an emergency for colonic hemorrhage is associated with excessive morbidity and mortality rates. An important factor contributing to morbidity and mortality that may be controllable is the amount of blood loss. Should total abdominal colectomy be the surgeon's operation of choice, it should be performed prior to 10 units of blood being needed. If this limit is passed, strong consideration should be given to performance of an ileostomy. PMID- 1928996 TI - Liver transplant for fulminant hepatic failure. AB - Fulminant hepatic failure is a challenging indication for liver transplantation because of associated multiple organ failure, profound neurologic abnormalities and coagulopathy. Sixteen patients have undergone emergent orthotopic liver transplantation for this indication at the University of Michigan, Ann Arbor, Michigan. Despite the associated problems, patient survival (68.2% at 2 years), intra-operative blood product utilization and duration of surgery were comparable to patients receiving liver transplants for other indications. All patients experienced complete recovery from preoperative neurologic abnormalities. Recurrent viral hepatitis did occur but did not result in allograft loss. For selected patients, orthotopic liver transplantation is excellent therapy for patients presenting with fulminant hepatic failure. PMID- 1928997 TI - Complications of coronary artery surgery in diabetic patients. AB - Postoperative mortality and morbidity of diabetic versus nondiabetic patients undergoing primary coronary artery bypass grafting (CABG) were analyzed. In 1988, 711 patients had CABG procedures, of which 565 were nondiabetic and 146 diabetic. The two groups of patients were statistically similar in regard to age, weight, tobacco and ethanol use, and preoperative levels of cholesterol, triglycerides, blood urea nitrogen (BUN), and creatinine. Preoperative serum glucose levels were significantly elevated in diabetic patients (182 vs. 106, P less than .001). Cardiac output, ejection fraction, and bypass, crossclamp time, and total operating room times were not different for the two groups. Emergent and urgent procedures had a significantly higher mortality rate than elective cases (11.3% and 6.6% vs. 1.7%, respectively; P less than 0.05), but this was independent of the patient's diabetic status. Women had a higher mortality rate than men (6.5% vs. 2.9%; P = 0.05) although within each gender group, there were no differences between diabetics and nondiabetics. There were 27 patients with complications in the diabetic group (18.5%) and 47 in the nondiabetic group (8.3%; P less than .001). The types of complications within the two groups differed in that wound infections (7.5%), postoperative arrhythmias (4.8%), respiratory failure (4.1%), and intra-aortic balloon pump use (4.1%) were significantly greater (P less than .05) in the diabetic patients compared to the nondiabetic (0.9%, 1.8%, 0.4%, and 1.4%, respectively). Occurrences of postoperative pneumothorax, reoperation, myocardial infarction, stroke, urinary tract infection, and pneumonia were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1928998 TI - Thermal laser assisted balloon angioplasty in lower extremity occlusive disease. AB - Results of Nd:Yag thermal laser assisted balloon angioplasty (LABA) in lower extremity occlusive disease were reviewed retrospectively in 23 patients and 28 lesions over a 1 year period. Indications for intervention were progressive claudication in 74 per cent and gangrene and/or rest pain in 26 per cent. Twenty four (86%) procedures were technically successful; however, there were only 15 (54%) clinical successes during the follow-up period (0.5-12.5 months). Complications occurred following ten (36%) procedures with one mortality (4%) unrelated to the procedure. Analysis of the nature and location of the lesions revealed five angiographic patterns with varying degrees of success. These are: Superficial Femoral and Popliteal: 1) short segment stenosis--2/3, 2) long multisegment stenosis--1/6, 3) total occlusion--7/9, 4) stenosis and occlusion- 2/4; Iliac: 5) stenosis--3/4. The only subsets of patients who appeared to benefit from LABA were those with short segment stenosis or isolated occlusions. Patients with good runoff also did well. Patients with poor runoff or multiple stenoses associated with diffuse disease did poorly. It is concluded that LABA has limited applications in the treatment of lower extremity occlusive disease. PMID- 1928999 TI - Injection sclerotherapy-induced esophageal strictures. Risk factors and prognosis. AB - Injection sclerotherapy (IS) has become an effective modality for the treatment of bleeding esophageal varices. Despite improvements in equipment, sclerosant solutions and operator technique, injection sclerotherapy-induced esophageal strictures (ISES) remain a significant cause of patient morbidity. To analyze the risk factors and prognosis of ISES, the records of 117 patients who underwent IS over a 6-year period at a single teaching institute were reviewed. The predictive value of multiple risk factors including the patient's age, Child's risk classification, previous bleeding episodes, etiology of varices, cumulative amount of sclerosant used, and the number of IS treatments were determined using ANOVA. A P value of less than 0.05 was considered significant. In all cases, a free-hand injection technique, flexible endoscopes and sodium morrhuate were used. During a mean follow-up period of 228 days (1-1,469 days), 41 patients (35%) died and 24 patients (20.5%) developed symptomatic strictures. The cumulative amount of sclerosant used (81.4 +/- 9.5 ml) and the number of IS treatments (6.5 +/- 0.7) required in the stricture group was significantly greater than in the nonstricture group (49.1 +/- 2.7 and 4.0 +/- 0.3, respectively). The risk of stricture formation did not correlate with the volume of sclerosant injected per treatment, cause of varices, number of previous bleeds, or Child's hepatic risk class. A mean of 3.6 +/- 4.5 dilations was required for treatment of established strictures and 18 patients (75%) required r 4 dilations. One esophageal perforation occurred following dilation. Mortality correlated with hepatic risk class as 30/41 (73%) of deaths occurred in Child's C patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929000 TI - Acute mesenteric venous thrombosis. Revisited in a time of diagnostic clarity. AB - Historically, mesenteric venous thrombosis (MVT) has been found during laparotomy or at autopsy. Improvements in computed tomography (CT) and ultrasound (U/S) may identify patients earlier in their clinical course. How has this altered the treatment strategy of the authors? This 10-year retrospective study of acute MVT consisted of 12 men and three women (average age 43). Presenting signs and symptoms were nonspecific in 10/15 patients resulting in multiple diagnostic tests. All CT scans (10) and angiograms (4) revealed mesenteric clot. U/S exams detected clot in 6/9 patients. The remaining five patients exhibited clinical signs requiring operations rather than diagnostic studies. The only consistent laboratory abnormality was an elevated white blood cell count in 12/15 patients. Management of MVT varied. Five patients, heparinized once the diagnosis was made, did not experience dysfunction from MVT. Ten patients were not initially treated with heparin and were divided into three groups. Three patients received neither heparin nor surgery and have had no sequelae. MVT contributed to the death of two patients. The remaining five patients were diagnosed in the operating room following bowel resection. Two of these patients received postoperative heparin and had a favorable outcome. Two of the three patients not heparinized after surgery suffered additional bowel infarction. MVT can present as nonspecific abdominal pain, but also as peritonitis requiring operation. CT and U/S can identify patients with early MVT. It appears that heparin has both a primary therapeutic role in early disease and a postoperative adjunctive role in advanced disease. With such care, these patients can expect an acceptable prognosis (86% survival). PMID- 1929001 TI - The rationale for incidental cholecystectomy during major abdominal vascular surgery. AB - The finding of gallstones during major abdominal vascular surgery warrants a critical decision regarding incidental cholecystectomy. The potential risk for vascular graft infection must be weighed against the risks of severe postoperative cholecystitis requiring surgery, a situation associated with significant morbidity and mortality. This report supports the safety of an incidental cholecystectomy, as long as the vascular graft is covered before the gallbladder is removed. The data also emphasize the hazards of not performing an incidental cholecystectomy for gallstones during major abdominal vascular surgery. PMID- 1929002 TI - Cervicothoracic vascular injuries. Presentation, management, and outcome. AB - One hundred consecutive patients with cervicothoracic vascular trauma were analyzed. The injury severity score, mechanism of injury, age, initial findings, management, and results were tabulated. There were 48 arterial and 61 venous injuries in the stable Group A patients, 11 arterial and 12 venous injuries in the unstable Group B patients, and three arterial and five venous injuries in the morbid Group C patients. Treatment included primary repair, resection with end-to end anastomosis, or ligation. Twenty-three patients developed postoperative complications, the most common being respiratory in nature. The overall mortality rate was six per cent. Five patients died during or immediately after operation of exsanguination, and one died of ischemic brain death on the seventh postinjury day. The usefulness of preoperative angiograms, especially in the detection of arteriovenous fistulas, is important in planning the surgical approach. The overall outcome was favorable. PMID- 1929003 TI - Atheroembolism. AB - Atheroembolism is an underdiagnosed and often preventable cause of acute arterial insufficiency. The patients suffering from atheroembolism require aggressive evaluation for a source of emboli and frequently surgical excision or exclusion of the source. The Keesler Air Force Base experience with atheroembolism over the past four years was reviewed. Fifteen patients representing 0.03 per cent of hospital admissions were diagnosed with atheroembolism. The embolic source as confirmed by arteriography was aortoiliac in eight patients (57%), femoropopliteal in six patients (43%), and unknown in one patient. Nine patients (60%) were treated surgically or with angioplasty. Three patients had toe amputations and one required a below-the-knee amputation. Only one death occurred that was secondary to unrelated disease. PMID- 1929004 TI - Biochemical performance of tapercut cardiovascular needles. AB - Standardized reproducible tests have been developed to determine the biomechanical performance of cardiovascular needles. The parameters used to assess performance were: 1) sharpness, 2) resistance to bending, and 3) ductility. Four comparable groups of tapercut and taper point cardiovascular needles were selected from different manufacturers for these biochemical studies. The results of this testing demonstrated that needle geometry, needle composition, and the manufacturer were important determinants of needle performance. When comparable needles were evaluated, the biochemical performance of cardiovascular needles manufactured by Ethicon, Inc. (Somerville, NJ) were superior to needles produced by other manufacturers. The superior performance characteristics of the cardiovascular needles produced by Ethicon, Inc. were related to their unique stainless steel alloy, American Society for Testing Materials 45500, which has greater yield and tensile strengths than the alloy used by the other manufacturers. This stainless steel alloy was ideal for the production of tapercut needles, which combined some of the features of a reverse cutting edge needle and taper point needle. Its very short cutting edges allowed it to penetrate the membrane at considerably lower penetration forces than were encountered with comparable taper point needles. In addition, the investigation indicated that the trocar point cardiovascular needles produced a large triangular defect whose diameter was much larger than that of the needle body. For this reason, the use of the trochar point needle is not recommended in cardiovascular surgery. PMID- 1929005 TI - Utility of femorofemoral bypass. Comparison of results with indications for operation. AB - Sixty-eight patients underwent femorofemoral bypass (FFB) at the University of Louisville Affiliated Hospitals over a 9-year period from 1980 to 1989. There were patients with acute ischemia requiring emergency operation, those with chronic ischemia following failed aortic reconstruction, good-risk patients with chronic ischemia who had FFB as the procedure of choice, and poor-risk patients who were unsuitable for other procedures. Patients operated on for acute ischemia had a significant number of infectious complications, with five of eight graft failures in this group due to infection. Primary patency rates were similar in all groups, with a 5-year primary patency of 42 per cent. Overall operative mortality was 4.4 per cent. Satisfactory limb salvage rates (75%) suggest that FFB is an acceptable option for providing inflow in patients with acute ischemia or for patients with a failed previous vascular prosthesis. FFB provides adequate inflow in poor-risk patients not suitable for aortic reconstruction, but patency rates do not warrant its use as a procedure of choice in good-risk patients. PMID- 1929006 TI - Duodenal webs in the adult. AB - Duodenal webs and diaphragms in the adult are congenital in origin and are rare. They are explained embryologically by the process of duodenal epithelial plugging and subsequent revacuolization. The symptoms may be insidious and appear late in life and consist of partial gastric outlet complaints. Two thirds of the patients will have other upper GI problems, some of which may be related to the antral distension and stasis produced by the web. Peptic ulcer disease is common but may resolve when the web is excised. Diagnosis can be made by contrast duodenography but is more definitive with endoscopy. Therapy should be directed at web excision if possible. Associated ulcer disease should be selectively approached. The results of therapy in the reported cases have been successful when the web is surgically excised without additional ulcer procedures. PMID- 1929007 TI - [Bioethics and pediatrics]. PMID- 1929008 TI - [HIV infection in the child. Bases for action in health assistance. Pediatric perspectives. Commitments of the Spanish Pediatric Association]. PMID- 1929009 TI - [Spanish Pediatric Association. Madrid. Human immunodeficiency virus infection. Spanish multicenter study]. AB - The results of an epidemiological survey in Spain organized by the "Spanish Pediatric Association" of children born to HIV+ mothers from 1981-1989 are presented. The objectives were, a) to document in the different parts of Spain the number of HIV+ children born to HIV+ mothers, and b) to identify the risk factors involved in the HIV infection. Only in public hospitals, a total of 1938 HIV+ children born to HIV+ mothers were identified. A systematic yearly increase of HIV+ newborns was evident since 1985. Madrid, Catalonia, Valencia, Basq and Andalucia communities incorporated 85% of all cases. 93% of mothers were IVDU and 51% of them were married. Prematurity occurred in 27% of cases and low birth weight in 33% of NB's. The rate of transmission in children over 18 months of age was 25.6% Breast feeding could be a risk factor in the transmission of HIV infection observed in children over 18 months of age. No other maternal risk factors responsible for the HIV transmission were identified. 12% of children died with AIDS. Clinical classification and evolution of HIV infection did not significantly differ from similar studies in other parts of the world. In spite of only public hospitals being involved, Spain has more identified HIV+ children than Italy, Switzerland, Federal Republic of Germany, United Kingdom, Sweden and Belgium combined. The pediatric centres with large number of cases require interdisciplinary pediatric specialized units to cope with the increase demand of medical services, now inadequate and insufficient. To fight drug use and HIV infection in Spain, health education and family support, are indispensable in trying to arrest the continuous spread the HIV infection. PMID- 1929010 TI - [Minor neurological signs and infantile hyperactivity: a new step in nosologic advances?]. AB - The many redefiniations of the hyperactivity has resulted in a more delimited concept with entity in intself. Neurological Soft Sings (NSS), which are relevant semiological data, have been evaluated from a sample with stricting criteria regarding hyperactivity. The sample results show a statistical correlation among NSS and those results got from controls. However the absence of NSS does not preclude the diagnostic. PMID- 1929011 TI - [Incidence and mortality of bronchopulmonary dysplasia]. AB - In this paper an attempt is made to analyze the variations in the incidence and severity of bronchopulmonary dysplasia (BPD) in our environment. A review has been made of the clinical records of premature infants with a diagnosis of BPD from 1979 to 1989, both inclusive. The existence of BPD was accepted when, after assisted ventilation with intermittent positive pressure for a minimum of 72 hours, there were respiratory difficulties, a compatible radiography of the thorax and requirements of over 0.21 FiO2 on the 28th day of life. Between 1985 and 1989, the incidence of BPD was similar to that of the five previous years (38.3% versus 42.3%), but mortality decreased (21.7% versus 36.3%). Other epidemiological data worth noting are the appearance of BPD in 2.6 per 1000 live newborns, 9.6 per 1000 newborns kept in hospital and 15.9% of premature infants treated with ventilation. BPD was found in 73% of newborns weighing less than 1.000 g, 41% weighing between 1000 and 1.499 g and only 16% of those weighing over 1,499 g. BPD was found in all newborns of less than 28 weeks, in 38% of those between 28 and 30 weeks and only in 4% of those aged more than 30 weeks. BPD appeared specially after hyalline membrane disease (30.7%). PMID- 1929012 TI - [Relationship between weight and tonsillectomy]. AB - 1,074 children, aged 11 and 14 years, have been examined. Their height and weight was measured, the %BMI was calculated, and the authors have known about performance of tonsillectomy in the past, in each schoolchild. It was found a significant relationship between tonsillectomy and overweight only in the male aged 14 years. A probability that stress after surgery leads to overweight is discussed. PMID- 1929013 TI - [Extra-hospital diagnosis in pediatrics. 6 years of computerized data]. PMID- 1929014 TI - [Fibrous hamartoma in infancy and childhood: study of 3 cases, one of them with multiple lesions]. AB - We present three cases of Fibrous Hamartoma of infancy, a pediatric benign fibrous proliferation. The patients were two females (10 months and 6 and half years old) and one male (18 months old). The location was characteristic in two cases: axillae and the fore aspect of the chest wall; the other case corresponds to three separated lesions located at the pubic region. The tumoral diameters were between 0.5 and 3.5 cms. Two of the five tumors were adhered to the skin and fascia. In only one case the lesion was congenital. As it usually occurs, the three cases were diagnosed after the pathological study of the surgically exercised lesions, because the rarity of this entity. That turns exceptional if the lesions are multiple. PMID- 1929015 TI - [Pallister-Killian syndrome and 12p tetrasomy: increased LDH-B activity]. PMID- 1929016 TI - [Lipoma of the corpus callosum associated with congenital rubella]. PMID- 1929017 TI - [Tuberculous encephalopathy]. PMID- 1929018 TI - [Hypouricemia and cellular immunodeficiency associated with purine-nucleoside phosphorylase deficiency]. PMID- 1929019 TI - [Macrocephaly and multiple hemangiomas in two brothers]. PMID- 1929020 TI - [Ciliary dyskinesia syndrome in childhood: apropos of a case]. PMID- 1929021 TI - [Gastric necrosis caused by acute dilatation of the stomach. A rare entity]. PMID- 1929022 TI - Increasing the dietary potassium intake reduces the need for antihypertensive medication. AB - OBJECTIVE: To determine whether an increase in dietary potassium intake from natural foods reduces the need for antihypertensive medication in patients with essential hypertension. DESIGN: Randomized, controlled trial with 1-year follow up. SETTING: Hypertension outpatient clinic of a university hospital. PATIENTS: Fifty-four patients with well-controlled hypertension, 47 of whom completed 1 year of follow-up. INTERVENTION: Patients were randomly assigned to one of two groups and were given dietary advice aimed at selectively increasing potassium intake (group 1) or at keeping their customary diet unchanged (group 2). During a 1-year follow-up period, drug therapy was reduced in stepwise fashion, according to a fixed protocol, provided that blood pressure remained below 160/95 mm Hg. MAIN RESULTS: Potassium intake was checked monthly by referring to 3-day food records and by measuring 24-hour urinary potassium excretion. Potassium intake increased in group 1 but did not change in group 2 (P less than 0.001). No change was observed in either urinary sodium excretion or in body weight. After 1 year, the average drug consumption (number of pills per day) relative to that at baseline was 24% in group 1 (95% Cl, 15% to 32%) and 60% in group 2 (Cl, 44% to 76%) (P less than 0.001). By the end of the study, blood pressure could be controlled using less than 50% of the initial therapy in 81% of the patients in group 1 (Cl, 66% to 96%) compared with 29% of the patients in group 2 (Cl, 10% to 48%) (P = 0.001). Patients in group 1 ended the study with a lower number of reported symptoms compared with patients in the control group (P less than 0.001). CONCLUSION: Increasing the dietary potassium intake from natural foods is a feasible and effective measure to reduce antihypertensive drug treatment. PMID- 1929023 TI - Treatment for cerebral toxoplasmosis protects against Pneumocystis carinii pneumonia in patients with AIDS. The Swiss HIV Cohort Study. AB - OBJECTIVE: To determine whether long-term maintenance treatment for toxoplasmosis protects against Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Cohort study. SETTING: Switzerland. PATIENTS: A total of 453 patients with human immunodeficiency virus (HIV) entered the Swiss HIV Cohort Study. Ninety-nine patients with cerebral toxoplasmosis but no previous or simultaneous P. carinii pneumonia were compared with 240 patients with AIDS and other severe opportunistic infections (Centers for Disease Control [CDC] stage IVC1 infection other than toxoplasmosis and P. carinii pneumonia) as well as with 114 patients receiving inhaled pentamidine in a study of primary pneumocystis prophylaxis in patients infected with HIV. MEASUREMENTS: Life-table analysis for P. carinii-free survival. MAIN RESULTS: Six of 99 (6%) patients with toxoplasmosis, 50 of 240 (21%) patients with other severe opportunistic infections, and 8 of 114 (6%) patients receiving inhaled pentamidine developed P. carinii pneumonia. Life-table analysis showed that the incidence of pneumonia was substantially lower in patients with toxoplasmosis compared with that in patients with other severe opportunistic infections and was similar to the incidence in patients receiving pentamidine as prophylaxis. Analysis of the medication records from patients with toxoplasmosis showed that pyrimethamine and sulfonamides were administered 50% of the time; pyrimethamine and clindamycin, 25% of the time; and pyrimethamine alone, 9.9% of the time but that only one of the six patients with toxoplasmosis who developed P. carinii pneumonia received pyrimethamine and sulfonamides in the month before diagnosis. CONCLUSION: Patients with cerebral toxoplasmosis have a low risk for subsequently developing P. carinii pneumonia. This decreased risk is probably the result of chronic suppressive treatment with pyrimethamine and sulfonamides. PMID- 1929024 TI - Reversible renal failure associated with angiotensin-converting enzyme inhibitors in polycystic kidney disease. AB - The renin-angiotensin-aldosterone system appears to play an important initiating role in the pathogenesis of hypertension in patients with autosomal-dominant polycystic kidney disease (ADPKD). Therefore, angiotensin-converting enzyme (ACE) inhibitors would appear to be appropriate therapy for hypertension in such patients. However, because ADPKD is a bilateral disorder, ACE-inhibitor therapy may worsen renal function, as occurs in patients with bilateral renal artery stenosis. We describe eight episodes of reversible acute renal deterioration in five patients with ADPKD, massive renal involvement, and chronic renal insufficiency. In all cases, ACE-inhibitor therapy either predisposed the patient to or precipitated the acute event. Two of the patients who had acute renal failure while receiving ACE-inhibitor therapy experienced a recurrence when rechallenged with such therapy. Furthermore, patients receiving combined therapy with an ACE inhibitor and a diuretic and patients who experience a cyst hemorrhage while receiving ACE inhibitor therapy are also at risk for reversible renal dysfunction. Caution is therefore recommended in using ACE inhibitors to treat hypertension in patients with ADPKD who are at high risk because of compromised renal function and massive cystic involvement. PMID- 1929025 TI - Screening for alcohol abuse using CAGE scores and likelihood ratios. AB - OBJECTIVE: To assess the performance of the CAGE (acronym referring to four questions, see below) questionnaire in discriminating between medicine outpatients with and without an alcohol abuse or dependence disorder. DESIGN: A cross-sectional design of a sample of consecutive patients who received both the alcohol module of the diagnostic interview schedule and the CAGE (Cut down, Annoyed, Guilty, Eye-opener) screening questionnaire. SETTING: The outpatient medical practice of an urban university teaching hospital. PATIENTS: All patients 18 years or older who signed a consent form approved by the university's institutional review board. MEASUREMENT: Calculation of the sensitivity, specificity, receiver operating characteristic (ROC) curve, and likelihood ratio for CAGE scores of 0 to 4. RESULTS: Thirty-six percent of the sample group met criteria for a history of alcohol abuse or dependence. A CAGE score of 2 or more was associated with a sensitivity and specificity of 74% and 91%. The calculated area under the ROC curve was 0.89, whereas the likelihood ratios for CAGE scores of 0 to 4 were 0.14, 1.5, 4.5, 13, and 100, respectively. These ratios were associated with posterior probabilities for an abuse or dependence disorder of 7%, 46%, 72%, 88%, and 98%, respectively. CONCLUSION: Clinicians can improve their ability to estimate a patient's risk for an alcohol abuse or dependence disorder using likelihood ratios for CAGE scores. PMID- 1929026 TI - Thoracoscopic talc poudrage pleurodesis for chronic recurrent pleural effusions. AB - OBJECTIVE: To assess the effectiveness of thoracoscopic talc poudrage for the treatment of chronic pleural effusions. DESIGN: Prospective evaluation. SETTING: Kaiser-Permanente Hospital. PATIENTS: Forty-seven consecutive patients with recalcitrant pleural effusions, referred for thoracoscopy. INTERVENTION: Patients received general or local anesthesia; 42 had a 7-mm rigid thoracoscopic examination followed by insufflation of 5 mL of talc. Patients then had chest tube drainage. MEASUREMENTS: We recorded clinical characteristics, final diagnosis, procedure-related pain and morbidity, days of hospitalization, patient reported degree of symptom relief, and chest roentgenographic results at 1, 3, and 12 months. All patients were followed for 16 months or until death. MAIN RESULTS: Of 39 evaluable patients, all reported prolonged relief of effusion related dyspnea. Radiographic results confirmed the elimination of pleural effusions in 34 patients (87%), including all 11 with benign conditions and 23 of 28 (82%) with malignancies. Treatment failed in three patients because of entrapped lung and in two patients with mesotheliomas whose effusions recurred more than a year after treatment. No procedure-related mortality or morbidity was found. Ambulatory patients required hospitalization for a mean of 3.9 days (range, 2 to 11 days). Mild pain was reported by some patients. The mean duration of chest-tube drainage was 2.7 days (range, 1 to 9 days). Patients with malignant disease lived an average of 12.4 months (range, 1 to 61 months) after the procedure. CONCLUSIONS: Thoracoscopic talc poudrage is an effective pleural sclerosing technique and is relatively painless. PMID- 1929027 TI - Recovery of adrenal function after failure resulting from traumatic bilateral adrenal hemorrhages. PMID- 1929028 TI - Cocaine-induced myocardial infarction in patients with normal coronary arteries. AB - OBJECTIVE: To review the reported cases of myocardial infarction temporally related to recreational and topical anesthetic use of cocaine, with special regard for underlying etiologic factors in patients subsequently found to have normal coronary arteries. DATA SOURCES: Personal records of three cases and a comprehensive literature review using MEDLINE and supplemented by Index Medicus and the bibliographies of case reports. DATA SYNTHESIS: A total of 114 cases of cocaine-induced myocardial infarction were identified. The coronary anatomy was defined by angiography or autopsy in 92 patients, 38% of whom had normal coronary arteries. In these 35 patients (average age, 32; range, 21 to 60 years), myocardial infarction typically involved the anterior left ventricular wall (77%). Moderate cigarette smoking with one or fewer associated coronary risk factors was prevalent (68%). Focal coronary vasospasm was shown convincingly in only two cases. Intracoronary thrombus was initially found on 9 of 11 angiograms (82%) done within 12 hours of the myocardial infarction. Experimental evidence suggests that cocaine has direct and indirect sympathomimetic effects on vascular smooth muscle, attenuates endothelium vasodilator capacity, exerts a potent depressant effect on cardiac myocytes, and promotes atherogenesis. CONCLUSIONS: Cocaine-induced myocardial infarction in patients with normal coronary arteries probably involves adrenergically mediated increases in myocardial oxygen consumption, vasoconstriction of large epicardial arteries or small coronary resistance vessels, and coronary thrombosis. Accelerated atherosclerosis and impairment of endothelium vasodilator function may occur after chronic cocaine use. PMID- 1929029 TI - Cost effectiveness of colorectal cancer screening in the elderly. AB - OBJECTIVE: To assess the cost effectiveness of a periodic program of colorectal cancer screening in the elderly. DESIGN: A model was constructed of four strategies for the periodic screening of persons 65 to 85 years of age. The effect of each strategy on life expectancy and health care costs was estimated under assumptions that were uniformly unfavorable to screening. Cost and added years of life were discounted at 5% per year. Cost per year of life gained from screening was calculated for each screening strategy. DATA SOURCES: Assumptions used in the model were based on a review of pertinent studies; those studies with results more unfavorable to screening were given more weight. Strengths and weaknesses of studies are discussed. MAIN RESULTS: A program of annual fecal occult blood testing (FOBT) in the elderly would detect at least 17% of the expected cases of cancer and could cost $35,000 per year of life saved. Screening schedules that include periodic sigmoidoscopy would prevent more cases of cancer but could cost between $43,000 and $47,000 per year of life gained. These estimates are based on uncertain assumptions, but results were not extremely sensitive to further relaxation of the values of the most uncertain assumptions. In no case did the cost per year of life gained from annual FOBT exceed $55,000 or did the cost per year of life gained from FOBT with sigmoidoscopy every 5 years exceed $61,000. CONCLUSIONS: Although colorectal cancer screening is costly in the aggregate, its potential medical benefits make it a reasonably cost effective preventive intervention for the elderly. PMID- 1929030 TI - Human immunodeficiency virus infection in women. PMID- 1929031 TI - Myonecrosis and myofibrosis in sickle cell anemia. PMID- 1929032 TI - Oral quinolone treatment for osteomyelitis. PMID- 1929033 TI - Quinolone prophylaxis during neutropenia. PMID- 1929034 TI - Diagnosing pulmonary embolism. PMID- 1929035 TI - Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. AB - OBJECTIVE: To determine the median response time to therapy with vancomycin alone or with vancomycin plus rifampin in patients with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis. DESIGN: Cohort analysis of a randomized study. SETTING: University medical center. PATIENTS: Forty-two consecutive patients with MRSA endocarditis were randomly assigned to receive either vancomycin (group I) or vancomycin plus rifampin (group II) for 28 days. MEASUREMENTS: Clinical signs and symptoms were recorded, and blood cultures were obtained daily to determine the duration of bacteremia. MAIN RESULTS: The median duration of bacteremia was 9 days (7 days for group I and 9 days for group II). The median duration of fever for all patients and for each treatment group was 7 days. Six patients failed therapy, including three patients who died 5, 6, and 9 days after therapy was started, respectively. The other three patients who failed therapy required valve surgery on days 2, 22, and 27, respectively. Although patients had sustained bacteremia, no unusual complications were seen in either treatment group, and most patients responded to continued antibiotic therapy. CONCLUSIONS: Slow clinical response is common among patients with MRSA endocarditis who are treated with vancomycin or vancomycin plus rifampin. Nevertheless, few complications appear to be related solely to this sustained bacteremia. PMID- 1929036 TI - Serum cholesterol as a prognostic factor after myocardial infarction: the Framingham Study. AB - OBJECTIVE: To determine the relation between serum cholesterol levels and the long-term risk for reinfarction, death from coronary heart disease, and all-cause mortality in persons who recover from myocardial infarction. DESIGN: Prospective, longitudinal study. SETTING: A geographically defined population-based cohort of adults participating in the Framingham Heart Study. PATIENTS: Men (n = 260) and women (n = 114), 33 to 88 years of age (mean age, 62 years), who had a history of myocardial infarction. MEASUREMENTS: A complete physical examination, including electrocardiographic evaluation, blood pressure measurement, height and weight measurements, determination of smoking habits, and casual determinations of blood glucose and serum cholesterol, was done approximately 1 year after recovery from initial myocardial infarction. Patients were followed after infarction for the occurrence of reinfarction or death (mean follow-up, 10.5 years; range, 0.8 to 31.6 years). MAIN RESULTS: The mean cholesterol level after infarction was 5.21 mmol/L (242.8 mg/dL); 20% of patients had levels below 5.17 mmol/L (200 mg/dL), and 22% had levels of 7.11 mmol/L (275 mg/dL) or more. Compared with patients who had cholesterol levels below 5.17 mmol/L, patients with levels of 7.11 mmol/L or more were at increased risk for reinfarction (relative risk, 3.8; 95% Cl, 1.6 to 8.7), death from coronary heart disease (relative risk, 2.6; Cl, 1.4 to 4.8), and all-cause mortality (relative risk, 1.9; Cl, 1.2 to 2.9) based on multivariate Cox regression analyses adjusted for other coronary risk factors. Intermediate cholesterol levels (5.17 mmol/L to 7.11 mmol/L) were generally not associated with increased risk. The association between elevated serum cholesterol and increased risk was strongest in men; however, elevated cholesterol levels were found to be most strongly related to death from coronary disease and to all-cause mortality in persons who were 65 years of age or more. CONCLUSIONS: Patients who have recovered from a myocardial infarction and who have high cholesterol levels are at an increased long-term risk for reinfarction, death from coronary heart disease, and all-cause mortality. Our results confirm the prognostic value of cholesterol levels measured after myocardial infarction and support the role of lipid management in this population. PMID- 1929037 TI - Long-term glucose control in patients with pancreatic transplants. AB - OBJECTIVE: To evaluate the long-term effect on blood glucose levels of successful transplantation of part or all of an intact human pancreas in patients with insulin-dependent diabetes mellitus (IDDM). DESIGN: Cohort study. SETTING: Referral medical center. PATIENTS: Thirty-seven patients with adequate data, representative of a group of 62 patients with functioning grafts (that is, insulin-independent) at 2 years after transplantation. The 62 patients came from a total of 178 patients in the University of Minnesota series as of July 1987, for a 2-year success rate of 35% (95% Cl, 27.8% to 41.8%). These patients were compared to two diabetic control groups (18 patients with IDDM under standard insulin treatment in a university diabetes clinic and 11 patients with IDDM whose pancreas grafts had failed) and to two nondiabetic groups (14 nondiabetic patients who received immunosuppressive drugs after kidney transplantation and 196 healthy control subjects). MEASUREMENTS: Glycosylated hemoglobin was measured by the high-pressure liquid chromatography method, as total A1 (Hb A1) and the A1C subfraction (Hb A1C); results were expressed as a percentage of total hemoglobin. MAIN RESULTS: Before pancreas transplantation, the 37 patients in the study group had a mean Hb A1 of 10.8%, consistent with moderate to marked hyperglycemia and not statistically different from the levels in the diabetic control groups. All 37 patients had values above the therapeutic target range of 5.4% to 7.4%. However, at 1 and 2 years after transplantation, the mean Hb A1 value had fallen sharply to 6.7% and 6.5%, respectively, well within target range (Cl of the difference, 3.4% to 4.8%; P less than 0.001). These levels did not differ from the mean Hb A1 in the nondiabetic kidney transplant recipients but were slightly above the 6.2% value for the 196 healthy controls (Cl of the difference at 1 year, 0.2% to 0.8%). Serial values were available on 6 subjects for 5 years; these values were all well within target range. As expected, Hb A1C values were parallel to those of Hb A1. CONCLUSIONS: Pancreas transplantation, in our successful cases, lowered glycosylated hemoglobin to normal or near-normal levels that were sustained for as long as 5 years. These results compare favorably with those in our patients on standard treatment, and also with those in similar patients on intensive control reported by others. Further effort to improve transplant methods appears to be warranted. PMID- 1929038 TI - Effect of octreotide on refractory AIDS-associated diarrhea. A prospective, multicenter clinical trial. AB - OBJECTIVE: To determine the efficacy and safety of octreotide for treatment of refractory, profuse diarrhea in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A prospective, open-label study. SETTING: Inpatient metabolic units of four university medical centers. PATIENTS: Fifty-one patients infected with human immunodeficiency virus (HIV) who had uncontrolled diarrhea (greater than or equal to 500-mL liquid stool per day) despite treatment with maximally tolerable doses of antidiarrheal medications. INTERVENTION: After initial baseline studies, patients received octreotide, 50 micrograms every 8 hours for 48 hours. If stool volume was not reduced to less than 250 mL/d, the dose of octreotide was increased stepwise to 100, 250, and 500 micrograms. MAIN RESULTS: Fifty men and one woman (mean age, 36.3 +/- 1.1 years) entered and completed the 28-day protocol (14 days of inpatient therapy and 14 days of outpatient therapy). Stool frequency and volume decreased significantly (6.5 +/- 0.5 stools per day on day 0 compared with 3.8 +/- 0.3 stools per day on day 21 [P less than 0.001] and 1604 +/- 180 mL/d on day 0 compared with 1084 +/- 162 mL/d on day 14 [P less than 0.001], respectively). Twenty-one patients (41.2%) were considered to be partial or complete responders (reduction in daily stool volume by greater than or equal to 50% of initial collections or reduction to less than or equal to 250 mL/d). Of the 21 responders, 14 (67%) had no identifiable pathogens at initial screening compared with 9 of 30 (30%) nonresponders (P less than 0.01). CONCLUSION: Patients with AIDS-associated refractory watery diarrhea, especially those without identifiable pathogens, may respond favorably to subcutaneously administered octreotide. This drug deserves further study in a randomized, placebo-controlled trial. PMID- 1929039 TI - Hiccups and achalasia. PMID- 1929040 TI - Ceftriaxone-induced cholelithiasis. PMID- 1929041 TI - Subspecialty training: is it financially worthwhile? AB - OBJECTIVE: To determine the financial return of additional training in a cognitive-oriented medical subspecialty (rheumatology) and in a procedure oriented medical subspecialty (gastroenterology) relative to general internal medicine. DESIGN: Analysis of existing data to compare lifetime discounted earnings of physicians in different medical specialties. PARTICIPANTS: General internists, gastroenterologists, and rheumatologists were surveyed. MAIN OUTCOME MEASURES: Using data from surveys conducted by Medical Economics and the American College of Rheumatology, we constructed lifetime earnings streams that allowed the calculation of the net present values of discounted lifetime earnings in general internal medicine, gastroenterology, and rheumatology. Net present values of lifetime earnings were calculated for each group at two discount rates. Sensitivity analyses were done to estimate how changes in relative income would affect calculations of the net present values. MAIN RESULTS: The average net incomes before taxes for general internists, gastroenterologists, and rheumatologists in 1988 were $115,825, $201,875, and $118,056, respectively. At 5% and 10% discount rates, the net present values of the estimated career earnings stream for additional training in gastroenterology relative to general internal medicine were + $1,101,863 and + $512,952, respectively; for additional training in rheumatology relative to general internal medicine, the respective values were - $84,748 and - $92,467. If the incomes of general internists were decreased by 3% and the incomes of gastroenterologists were decreased by 25% to reflect the effect of potential changes due to the resource-based relative value scale (RBRVS), or if gastroenterology training were increased to 3 years and rheumatology fellowship stipends were increased by 30%, large differences would still exist between the groups. CONCLUSION: Gastroenterologists have an extremely large return on their additional investment in training, but rheumatologists have a negative return. When considered exclusively as a financial decision, fellowship training in a cognitive-oriented medical subspecialty such as rheumatology is a poor investment. Even major changes in reimbursement policies will not affect the relative pecuniary attractiveness of procedure-oriented medical subspecialties. PMID- 1929042 TI - Wilson disease: clinical presentation, treatment, and survival. AB - OBJECTIVE: To evaluate the diagnostic features, clinical course, and overall long term survival of patients with Wilson disease. DESIGN: Retrospective cohort study with a mean follow-up period of 14.2 years. SETTING: A university medical center and a community hospital. PATIENTS: Fifty-one consecutive patients with Wilson disease were evaluated between 1957 and 1989. INTERVENTIONS: Patients were treated with D-penicillamine (600 to 1800 mg/d). Two patients with end-stage liver disease had liver transplantation. MAIN RESULTS: Initial symptoms occurred at a mean age of 15.5 years. At diagnosis, the most common neurologic signs were dysarthria, tremor, writing difficulties, and ataxia followed by hypersalivation and headache. Somatic symptoms included abdominal pain, hepatomegaly, splenomegaly, cirrhosis of the liver, and thrombocytopenia. The mean serum concentrations of ceruloplasmin and copper were 44 mg/L and 4.7 mumol/L, respectively. The mean basal urinary copper excretion was 5.5 mumol/d, and the mean hepatic copper concentration was 19.6 mumol/g dry weight. Free serum copper concentration (mean, 2.7 mumol/L) was a reliable indicator of disease and was useful in assessing the effectiveness of therapy (values less than 1.6 mumol/L). Treatment with D-penicillamine improved most of the hematologic and neurologic abnormalities but had little effect on hepatomegaly and splenomegaly and did not reverse cirrhosis. Two patients died of fulminant hepatic failure during the observation period, whereas two others with end-stage liver disease had successful liver transplantation and remain asymptomatic. Long-term survival of patients with Wilson disease was similar to that of age- and sex-matched controls. CONCLUSION: Our results suggest that long-term treatment of patients with Wilson disease with D-penicillamine can relieve symptoms and improve prognosis. PMID- 1929043 TI - Staphylococcus aureus and vancomycin: the sequel. PMID- 1929044 TI - Methotrexate and rheumatoid arthritis. PMID- 1929045 TI - Deep vein thrombophlebitis after acupuncture. PMID- 1929046 TI - Lowering the cost of prescription drugs. PMID- 1929047 TI - MRI: my resonant image. PMID- 1929048 TI - [Proteinuria selectivity index: prognostic value in idiopathic nephrotic syndromes]. AB - In INS, the histological appearance constitutes a classical prognostic element: minimal-change nephropathy (MCN) responds better to treatment than focal glomerulosclerosis (FGS) or IgM nephropathy (IgMN). However, this criterion is not consistent. We evaluated the prognostic value of the proteinuria selectivity index (SI): the ratio of IgG clearance to transferrin (Tf) clearance. Proteinuria was selective for an SI less than or equal to 0.01. In the 39 MCN, the SI ranged from 0.01 to 0.39 (median 0.10) and proteinuria was selective in 21 cases. In the 13 FGS and IgMN, the SI varied from 0.05 to 0.40 (median 0.22) and proteinuria was selective in 1 case (p less than 0.01 between these two groups). The SI ranged from 0.01 to 0.17 (median 0.07) for the 25 corticosensitive (CS) forms and from 0.08 to 0.40 (median 0.20) for the 27 corticoresistant (CR) ones (p less than 0.001). Twenty-four of the 30 MCN patients and 19 of 22 cases of selective proteinuria were CS. Multivariant analysis enabled the identification of variables predictive of the response to steroids. Age, sex and level of proteinuria had no such value. The predictive value of the SI was greater than that of the histological appearance (McFadden's R-square, 47 versus 22%, p less than 0.001). When the histological aspect was known, the SI provided additional precision, but the reverse situation was not true. The predictive curve of CS as a function of the SI was sigmoidal, therefore reflecting a homogeneous distribution, despite their different histological types.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929049 TI - [Ideal treatment of malaria attack: more questions than answers? Experience of a department of infectious diseases]. AB - The number of cases of malaria imported to western Europe from tropical areas is steadily growing, due to the increased number of people traveling to endemic regions and to the spread of Plasmodium strains resistant to chemoprophylaxis. This has prompted the WHO to frequently update its guidelines concerning preventive therapy. We report on 143 consecutive cases of benign attacks of malaria in patients returning primarily from western and central Africa. Plasmodium falciparum was responsible for 80% of the cases. Forty-one percent of the patients had followed their preventive regimen correctly; mefloquine failed in 3 of them. Three early relapses were observed after curative treatment, including 2 patients who had received intravenous quinine for more than 5 days. Because P. falciparum infection is potentially lethal, we suggest that the treatment of malaria attacks be optimized, by systematically dosing serum quinine levels, in order to adjust the administered doses, and, as a first-line therapy, by prescribing a combination of drugs to patients at high risk of resistance. PMID- 1929050 TI - [Postpartum thyroiditis]. PMID- 1929051 TI - [Neuroimaging of normal and pathological cerebral aging]. PMID- 1929052 TI - [Anatomo-clinical conference. Pitie-Salpetriere Hospital. Case No. 3-1991. Prolonged fever, polyneuropathy and diabetes in a 50-year-old man]. PMID- 1929053 TI - Primary biliary cirrhosis is a multisystem disorder. PMID- 1929054 TI - [Nephrotoxicity of cyclosporin. Clinical, physiopathological and histological aspects]. PMID- 1929055 TI - [Psychiatry and HIV]. PMID- 1929056 TI - [Cognitive evoked potentials at the stages II and III of human immunodeficiency virus infection]. AB - Neuropsychological and psychometric investigations have sometimes attested to and sometimes denied the existence of cognitive perturbations during the early phases of human immunodeficiency virus (HIV) infection (stages II and III of the CDC classification): strictly asymptomatic seropositivity or generalized lymphadenopathy. Therein lies the basis of the debate concerning the neurotropism of the virus and its deleterious effects on the central nervous system (CNS). We hoped to contribute to the resolution of this discussion by recording late evoked auditory potentials, which are composed of two types of components: exogenous responses attesting to the reception of stimuli by specific sensory areas of the CNS, regardless of their informative value for the subject; and endogenous responses that occur later, appearing when the subject is required to distinguish between different stimuli, for example, counting high-pitched sounds randomly distributed among low-pitched ones. The latter responses, which have been most extensively studied for wave P300, are associated with cognitive functions, and alterations of the evoked cognitive potentials have been observed during the course of demential syndromes of various origins. Fifteen individuals were subjected to the protocol for recording long-latency, evoked auditory potentials. These studies were completed by a battery of psychometric tests, two methods for evaluating depression and an assessment of the anxiety level. The results showed a significant lengthening of the latency of wave P300 in the seropositive subjects. This prolongation also affected one of the exogenous components, i.e., wave P2. In addition, their intelligence quotients, regardless of whether the IQ explores the so-called crystallized component or the fluid component of intelligence, were not significantly different from those of the general population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929057 TI - [Neurotrophic ulcerations in cerebral toxoplasmosis in AIDS]. PMID- 1929058 TI - [Hemorrhagic forms of cerebral toxoplasmosis in human immunodeficiency virus infection. 4 cases]. PMID- 1929059 TI - [Absence of value of omega-3 in patients with human immunodeficiency virus infection]. PMID- 1929060 TI - [Mycobacterium avium/intracellulare complex mediastinal lymphadenopathy excluding HIV infection]. PMID- 1929061 TI - [Primary hypothyroidism with hyperprolactinemia and pseudoprolactinoma in 2 sisters]. PMID- 1929062 TI - [Thromboembolic manifestations of Crohn's disease]. PMID- 1929063 TI - [Interactions between sleep, ventilatory disorders and arrhythmia in Cheyne Stokes respiration]. PMID- 1929064 TI - [Rare neurologic forms disclosing Horton's disease. 2 cases]. PMID- 1929065 TI - [Urologic manifestations in Wegener's disease]. PMID- 1929066 TI - [Demand for care in traumatic war neuroses]. AB - Psychiatrists who must take care of patients suffering of Post Traumatic Stress Disorders are often surprised in front of the strength of repetition of the related frightful experience. Therapeutics methods which are more often used (Abreaction and Narcissism reconstruction by varied technics) have showed their limits. Leaning on their experience and referring to psycho-analytic teaching, the authors show the interest of the individual psychotherapy. They propose not to be strongly affected by the massive aspect to the "trauma" and to permit as far as possible the installation of the transfer. PMID- 1929067 TI - [Depression and crime. Review of the literature and original cases]. AB - After mentioning the classical studies of Freud, Fenichel, De Greeff and Lagache, the author reviews contemporary works on the following relationships: depression homicide; murder-suicide. Two cases of familial murder committed during a state of depression are then studied in depth. Two remarks from previous analyses are then made: the underestimation of the factor of depression in the homicidal act; and the need for reforming the practice of penal psychiatric survey. The author concludes that depressive and suicidal tendencies should be included among the best predictors of psychiatric dangerousness. PMID- 1929068 TI - [Philippe Pinel (1745-1826) a tonsured cleric]. AB - Philippe Pinel received an excellent education from the Fathers of the Christian Doctrine whose recently discovered library is here analyzed. New facts about his first teacher, Jean-Pierre Gorsse, indicate that he, too, was a student of the Doctrinaires and that a benefice requiring the tonsure passed to Pinel when Gorsse married in 1759. PMID- 1929069 TI - [Disaster theory and psychopathological forms]. PMID- 1929070 TI - [Why confuse illness and age? Why refuse age and illness?]. PMID- 1929071 TI - [A catamnestic study of 73 patients hospitalized in psychiatric units]. AB - The purpose of this study was to describe, among 73 patients, the evolution of their symptoms and the conditions of their psychiatric follow-up care within two years after their first hospitalization. These patients (who had never been hospitalized before in any type of psychiatric unit) were admitted in the psychiatric emergency unit of a general hospital. Five groups were characterized: affective disorders, adaptative disorders, psychotic disorders, substancious disorders, and anxious disorders. The group of affective disorders showed only few improvements in symptoms, although a longer and more regular follow-up care was sustained. The adaptative disorders group had a good prognosis despite a high frequency of follow-up interruptions. Finally, in spite of very frequent symptom aggravations, the group of delusional disorders presented a bad acceptance of psychiatric treatment. PMID- 1929072 TI - [Hierarchic analysis of MADRS]. PMID- 1929073 TI - [MADRS in 59 subjects without mental disorders. A comparison with a sample of patients with depression]. PMID- 1929074 TI - [Nosography and epidemiology of puerperal psychoses]. PMID- 1929075 TI - [Mother-child hospitalization in an emergency center?]. PMID- 1929076 TI - [Mother-child hospitalization in the adult psychiatric unit of Hopital Paul Brousse]. PMID- 1929077 TI - [Information on sexuality during pregnancy and postpartum]. PMID- 1929078 TI - [Value of the psychologist's intervention in the maternity of a general hospital]. PMID- 1929079 TI - [Experience of puerperality in women with psychiatric background]. PMID- 1929080 TI - [Psychological aspects of obstetrical echography]. PMID- 1929081 TI - [A survey on the somatic symptoms of couvade]. PMID- 1929082 TI - [The father or the child]. PMID- 1929083 TI - [Post-partum blues and affective blunting]. PMID- 1929084 TI - [Puerperal psychoses. Autonomy or dismantlement? A contribution to the nosographic discussion]. AB - Since the DSM III has contested the nosographic autonomy of puerperal psychosis, various works have confirmed that exist a genuine similarity between the post partum severe crisis and the psycho-biological definition of psychosis. The dismantling is nevertheless not always total nor convincing because the state of pregnancy and birth giving modify deeply the women personality as ist was before as well as capacity to react to events. Three cases are reported by the authors in confirmation of the above. PMID- 1929085 TI - [Puerperal psychosis and/or delusions crisis]. PMID- 1929086 TI - [Recurrent puerperal psychosis and calcifications of the basal ganglia. Apropos of a case]. PMID- 1929087 TI - [Treatment of puerperal mental disorders and dysfunctioning of the early mother child relation at the maternity of the General Hospital Center of Charleville Mzieres]. AB - The psychiatric care of the motherhood disorders and of their consequences over the early mother-child relation has become necessary from P.C. Racamier's writings and after studies about maltreated young children. Maltreatment has been defined by us in a broad sense, that is to say from marked cruelties to neglect, including various forms of aggressiveness and rejection. The Maternity Hospital, as a structure, has been considered as a well-suited place because nearly all the future mothers of the department are delivered there. The work undertaken for one year at Charleville-Mezieres Maternity Hospital is clinically described, with its advantages and its difficulties, revealing the increasing need of a correctly trained multidisciplinary staff, even specialized, which could ensure psychiatric care over a period long enough to be effective. PMID- 1929088 TI - [Role of electroshock therapy in puerperal mental disorders]. AB - Ten cases of psychotic patients requiring electroconvulsivotherapy (ECT) are reported during pregnancy and puerperium. The interest and the safety of ECT are confirmed. ECT is principally indicated in severe cases and in typical or atypical mood disorders. PMID- 1929089 TI - [Law and pathology of the puerperium]. PMID- 1929090 TI - Effects of IAL and Healon on postoperative intraocular pressure after cataract surgery with intraocular lens implantation. AB - A randomized controlled study was done on 60 patients, divided into three groups, who underwent extracapsular cataract extraction and intraocular lens implantation. The aim of the study was to investigate the effect on postoperative intraocular pressure (IOP) of IAL left in situ compared with IAL or Healon removed after surgery. The IOP was monitored three, six, 12, and 24 hours and seven days after surgery. In general, there was a similar trend in IOP in the three groups with increasing values starting three hours after surgery and normal values reached around 24 hours. No significant statistical difference was found when IAL was removed compared with Healon removed or IAL left in situ compared with Healon removed. No differences were found in the presence of an inflammatory reaction or its severity among the three groups 24 hours after surgery. We believe that IAL can be used in cataract surgery without removing it at the end of the operation, thus simplifying surgical maneuvers and reducing surgical risks. PMID- 1929091 TI - Idiopathic central serous choroidopathy in a patient with pericentral pigmentary retinal degeneration. AB - A 35-year-old man with pericentral pigmentary retinal degeneration also had idiopathic central serous choroidopathy OU. This case report describes a rare coexistence of two independent diseases. PMID- 1929092 TI - Antituberculosis therapy in the treatment of peripheral uveitis. AB - Tuberculous uveitis usually appears as chronic anterior uveitis or disseminated choroiditis. From 1982 to 1989, we conducted a retrospective study of 23 patients with presumed tuberculous uveitis. All patients had a positive tuberculin purified protein derivative skin test. The diagnosis was based on history, positive skin test, and physical examination. We excluded other conditions that could induce uveitis, based on the absence of signs, symptoms, or laboratory results suggesting any other diagnosis. Tuberculous uveitis was also considered in the differential diagnosis when progressive ocular inflammation was resistant to corticosteroid therapy. The patients received the following treatment: (1) isoniazid (300mg/day) and rifampin (600mg/day) for nine to 12 months, (2) ethambutol (1200mg/day) in some cases for two to three months, and (3) corticosteroids orally where indicated. In cases with anterior uveitis, we added local instillation of mydriatics and corticosteroids. There was no regression, nor were there any side effects of antituberculosis therapy in all 23 patients. We noted clinical improvement in 78% of cases. Five patients had other conditions (cataract or retinal detachment) that worsened their vision. PMID- 1929093 TI - Unilateral proliferative diabetic retinopathy and uveitis in the fellow eye: report of a case. AB - We report the case of a young man with a 20-year history of insulin-dependent diabetes mellitus, proliferative diabetic retinopathy OD, and uveitis OS. None of the common reported causes contributing to this difference between eyes was present. No features of diabetic retinopathy appeared OS after a follow-up of 36 months. This is the first case, to our knowledge, in which uveitis appeared to be associated with an asymmetric presentation in diabetes. PMID- 1929094 TI - Preoperative antibiotic and povidone-iodine preparation of the eye. AB - We compared gentamicin 0.3% one drop every three hours the night before and the morning of surgery ("half-day regimen") with the same drug one drop qid for three days ("three-day regimen") in 15 eyes undergoing intraocular surgery. Conjunctival cultures of both groups taken before povidone-iodine preparation showed mean colony counts of 3.67 +/- 0.82 in the half-day regimen versus 1.0 +/- 0.43 in the three-day regimen. Conjunctival cultures taken after the administration of a povidone-iodine 5% preparation showed 7.17 +/- 3.52 and 2.75 +/- 0.88, respectively, in the two groups. Although there was a statistical difference in colony counts, topical gentamicin 0.3% given the night before and day of surgery had comparable low colony counts with the three-day course. The 5% povidone-iodine solution was not effective in reducing bacterial flora although it did eliminate all fungal colonies. PMID- 1929095 TI - Evaluation of glare in normal and pseudophakic subjects. AB - It has been difficult to document the subjective complaint of glare. Devices to quantify this problem include the Miller-Nadler glare tester (MNGT) and the brightness acuity tester (BAT). We used these devices to evaluate a group of pseudophakic subjects (15 eyes with posterior-chamber intraocular lenses) and a group of normal subjects (32 low myopic eyes). A subject's ability to discern contrast with a background glare source is measured as a percentage with the MNGT. The number of lines lost on the Snellen chart as a light is brightened progressively over the line of vision is the BAT score. A Wilcoxon signed-ranks test showed no significant change without correction (SC) to with correction (CC) with the BAT but was significant at P less than .001 with the MNGT. The BAT scores for the normal group CC (mean, 0.59) compared with the intraocular lens group CC (mean, 3.0) with the Mann-Whitney U test showed a statistically significant difference (P less than .001). There also was a difference with the MNGT between normal group CC (mean, 5.1%) and pseudophakic group CC (mean, 8.9%) at P less than .001). These results suggest that pseudophakic subjects have marked visual dysfunction secondary to glare. The BAT, however, showed a more easily quantifiable change unaffected by spectacle correction. PMID- 1929096 TI - Indications for caesarean section: results of a local study. AB - Records from 6820 deliveries of three year (1980, 1985 and 1988) were reviewed in order to collect informations on cesarean section trend and its indications in a public hospital of Milan, Italy. Data show the magnitude of the phenomenon in the wards considered and an evident increase of cesarean section proportion from 1980 (18.6%) to 1988 (26.9%). The frequencies of major indications has not changed much apart from dystocia which has decreased and previous cesarean section which has increased. A logistic regression model was performed to evaluate cesarean section risk factors. Distribution of cesarean section during the days of the week show higher (about 30%) cesarean section proportion Monday through Thursday compared with low proportion (20% or less) on Fridays and weekend-days; this suggesting a possible high proportion of pre-programmed cesarean section. PMID- 1929097 TI - [New prospects in the combined use of tumor markers in epithelial neoplasms of the ovary]. AB - The Authors have studied the haematic levels of CA 125, CA 19-9, CA 50, CEA, and TPA in 23 women with ovarian cancer and in 14 healthy women. The results showed as the simultaneous use of CA 125 and TPA can premise the diagnosis of ovarian cancer in high percentage. PMID- 1929098 TI - [Correlations between trophism of the external genitalia and hormone levels during menopausal age]. AB - In a case group of 341 perimenopausal women the following signs of reduced trophism of external genitalia have been studied: mons pubis hair rarefaction, pale mucosae, labia minora edge thinning, and labia minora involution, as well as their correlation with age, time lapse after the menopause, and plasma FSH, LH, progesterone and 17-beta-estradiol. Signs of reduced trophism appear to be present even in the younger considered ages, but a positive trend with age is shown. The passage from less than one year inveral from the menopause to one to three years interval shows the most marked increase in the appearance of involutional aspects, but at six years from the menopause one fourth of the women still show normal trophism of the external genitalia. An inverse relation with 17 beta-estradiol levels is shown for pale mucosae and labia minora edge thinning while the trend of mons pubis hair rarefaction shows no relation with the hormone level. An inverse relation is shown for progesterone levels and the trend of mons pubis hair rarefaction, while for the other signs of reduced trophism the same kind of relation as for 17-beta-estradiol was shown. FSH and LH levels show an inverse relation with "normal" trophism, a direct relation with pale mucosae and labia minora involution, and no relation with mons pubis hair rarefaction and labia minora edge thinning. PMID- 1929099 TI - [Climacteric syndrome: comparison of several secondary therapies]. AB - During a first one year period a random treatment for climacteric symptoms with "Estriol vaginal cream" vs "Trazodone and Estriol vaginal cream" and, after it and only in patients not complaining of dyspareunia, with "Trazodone" vs "Veralipride" has been conducted. After the first year all women complaining of dyspareunia were treated with Estriol vaginal cream. Eighty women were enrolled in the five treatment groups. After three months of treatment, a good remission of symptoms was shown, with differences in relations to treatment schedules. Dyspareunia subsided for more than 70% in women treated with Estriol vaginal cream (either by itself or in association), and Estriol vaginal cream achieved the best response from the highest number of the considered symptoms, besides being the only active treatment in insomnia. A good answer on hot flushes and "irritability, anxiety, depression" was obtained by Trazodone, while Veralipride showed to be more active on all neurovegetative symptoms (hot flushes, sweatings, tinglings, palpitations, astenia). PMID- 1929100 TI - [Embryonal and early fetal growth after in vitro fertilization and embryo transfer]. AB - Echographic examination allows correlations between crown-rump length and gestational age. In this study the embryonic and early fetal growth after in vitro fertilization and embryo transfer was evaluated by ultrasound (U.S.) marks. 97 measurements in 54 pregnancies between day 39 and 80 after successful fertilization has been performed. Early fetal growth retardation was detected by U.S. when compared to the Robinson curve for normal pregnancy and confirmed after correction for the instrument error. This delay of 3, 3.5 days disappears around the 13 week of pregnancy and is not related to the baby weight at birth. An implantation delay may explain this difference in growth rate between normal and after F.I.V. and E.T. pregnancies. PMID- 1929101 TI - [Experimental approach to nutritional problems in chronic renal insufficiency]. AB - The many published studies of experimental chronic renal failure (CRF) include a few findings which are similar to those reported in children with the naturally occurring disease. Experimental CRF has proved a useful model for investigating changes in eating behaviors: lack of appetite for sweet foods and selection of foods with high protein contents was comparable to behaviors exhibited by children. Optimal protein intake was found to be close to the minimum recommended intake for "optimal" growth (different from maximum growth in rats). Excessive protein intake had detrimental effects on renal function and growth with conventional dehydrated feeds, but water intake may have a greater impact than blood urea nitrogen and acidosis. A 50% reduction in protein intake with adequate amounts of essential amino acids ensured normal growth and slowed progression of renal lesions. Replacement of protein by mixtures of ketoanalogs was more likely to be responsible for growth failure; where similar growth rates were achieved, there was no evidence of a beneficial effect on renal lesions. Diets with high sucrose contents were poorly tolerated by CRF rats and were associated with fructose "intolerance" and reduced liver energy stores. PMID- 1929102 TI - [How to interpret blood pressure values obtained in children and adolescents]. AB - As soon as blood pressure (BP) values are available for a child or teenager, a multitude of questions arise. The values obtained need to be interpreted, validated, and made use of. Values measured in an individual can be interpreted only by comparison with the results of measurements performed using the same protocol in an adequate sample of subjects with similar life styles. The value of reference to stature rather than age has been well established. Studies of BP measured at rest are the most widely used. The validity of blood pressure values is dependent on measurement technique but is also related to the problem of intraindividual variability. To address this problem, blood pressure values have been measured not only at rest but also during standardized stimulation tests and throughout the 24-hour period (ambulatory BP measurements). Studies using these techniques in children and adolescents are still scant. Longitudinal studies of the mean-term and long-term reproducibility of these measurements are needed. Until results of such studies are available, blood pressure measurements in non resting subjects will be mainly useful for evaluating patients with borderline BP values at rest and for monitoring the effect of therapy. The response to blood pressure values believed to be borderline should include evaluation of factors which influence BP values as well as of the other risk factors for cardiovascular disease. The predictive value of blood pressure levels is fairly poor in childhood. Correlation coefficients between values obtained five years apart approximate 0.25. These coefficients increase with age and finally level off at 0.4-0.5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929103 TI - [Value of ambulatory blood pressure monitoring in borderline hypertension in the child]. AB - This study was undertaken to evaluate the reliability of ambulatory blood pressure monitoring (ABPM) in children and its diagnostic value in teenagers with borderline hypertension. The apparatus used was a Nippon Colin (NC) ABPM 630 which simultaneously obtains BP levels by the auscultatory and oscillometric methods. Among 61 children (mean age 12 +/- 3 years), proportion of measurement failures was 14% (470/3399) for oscillometry, 26.5% (893/3360) for auscultation, and 2.7% for both methods together. Comparison of conventional auscultatory blood pressure measurements (mercury manometer) and simultaneous NC-auscultatory BP values (50 pairs) showed slightly lower diastolic blood pressure values with the NC monitor (-3.8 +/- 4.9 mmHg, p less than 0.01). Comparison of blood pressure values provided by the two NC methods (1580 pairs) demonstrated slightly higher systolic blood pressure values (+2.5 +/- 4 mmHg; p less than 0.001) and slightly lower diastolic blood pressure values (-5 +/- 4 mmHg; p less than 0.001) with the oscillometric method. Thirty-four ambulatory blood pressure recordings were obtained in 28 children (mean age 13.3: range 8-17) with outpatient clinic blood pressure values suggestive of borderline hypertension. Numbers of ambulatory blood pressure readings were 44 +/- 5 during the day and 9 +/- 1 during the night. The mean of daytime blood pressure values was compared with reference blood pressure values obtained at rest in normal French children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929104 TI - [Renal artery pathology and its therapeutic indications in the child]. AB - Between September 1955 and January 1990, 94 pediatric patients were managed for renovascular hypertension caused by renal artery occlusive disease. Patients (50 boys and 44 girls) were aged 4 days to 17 years (median age: 7 years). At initial evaluation, 34 patients had symptoms of hypertensive encephalopathy or acute heart failure, 36 had moderate symptoms, and 24 were symptom-free. Sixty-five cases were classified on the basis of clinical, radiological, and histological features, as follows: neurofibromatosis (17), fibromuscular dysplasia (11), diffuse arterial calcified elastopathy (11), renal artery thrombosis (10), Williams syndrome (4), Takayashu disease (3), and miscellaneous diseases (9). In the 29 remaining patients, classification was based only on radiological features: causes included unilateral renal artery stenosis (15), bilateral renal artery stenosis with or without aortic stenosis (11), and miscellaneous disorders (3). Surgical treatment consisted in 47 renal revascularization, procedures (14 aortorenal bypasses, 8 aortorenal reimplantations, 9 anastomoses in the upper mesenteric arterial system, 7 autotransplantations, 4 resection-reanastomosis procedures, and 5 miscellaneous procedures). Renal revascularization failed in 15 cases (32%) (because of thrombosis in 14 cases and dehiscence in one). Residual or recurrent stenosis was seen in 7 arteries, whereas the anatomic result was satisfactory in 25 arteries (53%). Blood pressures returned to normal in 16 of 40 (40%) patients successfully treated by revascularization. An additional 25 patients recovered normal blood pressure values after primary nephrectomy (21), partial nephrectomy (4) or nephrectomy after failed renal revascularization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929105 TI - [Alternate day corticosteroid therapy and growth in renal transplant children]. AB - Corticosteroid therapy is probably the main factor inducing stunted growth in pediatric renal transplant recipients. Results of a randomized study in 35 children who received their kidney between 1981 and 1984 are reported. All patients had normal renal function and were taking azathioprine and prednisone to ensure immunosuppression. Eighteen months after transplantation, patients with normal renal biopsy results were randomized to receive further daily corticosteroid therapy (group A) for an additional year or to alternate-day corticosteroid therapy (group B). Chronologic age, bone age, renal function, and previous growth retardation were strictly comparable, in the two groups. During the first year, only prepubertal children in group B exhibited catch-up growth. In children undergoing puberty, annual statural gain was greater in group B (5.6 cm versus 3.2 cm in group A: p less than 0.001). Group A children were switched to alternate-day corticosteroid therapy one year after initiation of the study and exhibited improved growth after this change. No patient had renal function deterioration under alternate-day corticosteroid therapy, throughout the study period. Alternate-day prednisone should be offered to pediatric renal transplant recipients with satisfactory renal function as a mean for protecting growth potential. PMID- 1929106 TI - [Gonad function and sexual activity in male renal transplant patients]. AB - Gonad function and sexual activity were evaluated in 44 young male adults who received a kidney shortly before or during adolescence. All patients were growth retarded (-2.2 SD). Volume of the testes was decreased less than 12 ml, i.e, less than 10th centile) in 47% of patients, whereas hormone levels (testosterone, FSH, LH, and prolactin) were within the normal range. Oligospermia or azoospermia was found in 10 of 11 tested patients. Testicular function and sperm count were negatively correlated with renal function. Age at first ejaculation was increased and 57% of patients had never had sexual intercourse, although all patients reported normal sexual drive and normal erections. PMID- 1929107 TI - [Longitudinal study of histocompatibility antigen expression in renal transplants followed for 10 years]. AB - Using monoclonal antibodies against class I and class II (DR antigen) major histocompatibility complex antigens, 65 renal transplant biopsies from 21 recipients whose renal transplants survived ten years or more were studied. Seven biopsies were performed while acute rejection of the renal transplant was under way. The other biopsies were carried out on a routine basis, 6 months (10 biopsies), 2 years (15 biopsies), 4 years (12 biopsies), and 10 years (21 biopsies) after transplantation. Semiquantitative evaluation of fibrous tubulointerstitial lesions was carried out on the biopsies taken after ten years. During episodes of acute rejection, strong expression of class I and class II HLA molecules by transplant tubule epithelial cells was found. When there was no acute rejection, tubule expression of class I and class II HLA molecules was more common in earlier biopsies as compared with later biopsies. In the long-term, persistence of DR antigen in tubule epithelium was associated with increased severity of fibrous tubulointerstitial lesions. A last remarkable finding in some patients was loss of expression of class I antigens in tubule cells from transplants with the longest survivals. PMID- 1929108 TI - [Clinical evaluation of 70 pediatric renal transplants after 10 to 17 years]. AB - Among 149 kidneys transplanted in 141 children and teenagers aged 4 1/2 to 20 years, from November 1972 through December 1979, 70 (47%) were still functioning after ten years (67/145 cadaver donor grafts and 3/4 living related donor grafts). Medical and social status at the last follow-up visit (10 to 16 1/2 years after transplantation; m = 12 years) was analyzed. Patients were divided into five groups on the basis of glomerular filtration rate (GFR; ml/min/1.73 m2) and blood pressure (BP): 1) GFR greater than 80 ml and normal BP: 23 patients (33%); 2) GFR in the 60-80 ml range and/or high BP: 24 patients (34%/3) GFR in the 40-60 range: 6 patients; 4) GFR in the 15-40 range: 7 patients; and 5) hemodialysis restarted 10 1/2 to 13 years after transplantation. Mean adult stature was 155.7 +/- 10.4 cm in males and 149.8 +/- 10 cm in females. Osteoporosis was found in 88% of patients who underwent bone density quantitation. Twenty-four per cent of patients had aseptic osteonecrosis with variable degrees of impairment as a result. Chronic HBsAg carrier status was found in 37% of patients and was accompanied with persistent cytolysis in half the cases. Only one malignancy was seen (carcinoma of the urinary bladder in a child under cyclophosphamide). Six deaths were recorded between 10 and 13 years after transplantation; causes included septicemia (2 cases), cancer (1 case), hepatitis B (1 case), cerebral cystinosis (1 case), and unexplained sudden death (1 case).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929109 TI - [Long term results in 70 pediatric renal transplants after more than 10 years. Histological study]. AB - A clinicopathologic study of 41 biopsy specimens from renal grafts transplanted at least ten years earlier showed normal findings or only mild tubulointerstitial lesions in 63% of cases. Results confirmed the good prognostic value of renal graft biopsy performed ten years after transplantation. A very close correlation was demonstrated between histologic evidence of chronic rejection (interstitial fibrosis, tubular atrophy, and fibrous endarteritis) and long-term graft outcome. Severity of interstitial fibrosis was apparently a more reliable indicator of prognosis than severity of fibrous endarteritis. Among 16 patients with a history of acute rejection, none had residual parenchymatous lesions. In contrast, among patients with major tubulointerstitial and/or vascular lesions, most had previously experienced one or several episodes of acute rejection. Evidence of allograft glomerulopathy was seen in approximately one case in four (11 patients). Among these patients, only eight had proteinuria and only four lost their graft. Among the four patients who developed recurrent membranoproliferative glomerulonephritis (type I in three cases and type II in one case), three lost the deposits previously detected by immunofluorescence, probably as a result of immunosuppressive therapy. PMID- 1929110 TI - [Course of renal lesions in disseminated lupus erythematosus]. AB - Clinical and biological features, histologic findings, and outcome were studied in 32 children with systemic lupus erythematosus who underwent at least two renal biopsies during the course of their disease. Results showed that renal biopsy was a useful aid for therapy in that it demonstrated the presence or absence of disease activity, but was unhelpful for predicting the long term outcome. Repeat renal biopsies proved an excellent means for monitoring the course of the nephropathy. This study showed that the various patterns of glomerulonephritis seen in SLE may exhibit changes over time, with either improvement or progression. Regression of lesions was seen mainly after treatment, whereas progression was associated with renal or extrarenal exacerbations of the disease. The absence of clinical improvement may reflect transformation to histologic forms which are unresponsive to therapy. PMID- 1929111 TI - [Unfavorable outcomes in disseminated lupus erythematosus in children. Cooperative study in the Paris region]. AB - Pediatric cases of systemic lupus erythematosus with an unfavorable outcome (terminal renal failure requiring chronic hemodialysis, or death) assembled during a retrospective multicenter study of pediatric SLE in the Paris metropolitan area were analyzed. Seven patients (6 girls, 1 boy) were entered into a chronic hemodialysis program. Four had diffuse proliferative glomerulonephritis, the pattern of glomerular disease classically responsible for end-stage renal failure. The other three patients had membranous glomerulonephritis with active segmental lesions, a form of glomerulopathy whose severe prognosis deserves to be emphasized. Nine other patients (8 girls, 1 boy) died. In six patients, death occurred as a result of a flare with malignant hypertension and progressive renal failure (1 case), pancreatitis (1 case), encephalopathy (2 cases) or cardiomyopathy (2 cases). An infectious disease (tuberculosis, mumps) was apparently the cause of the two cases of encephalopathy. One girl died as a result of a hemorrhagic syndrome with a cerebral hematoma. Two other girls died at home. Overall, among 111 children with SLE 14% had an unfavorable outcome. Sex and age at onset seemed to have no bearing on prognosis. Patients with renal involvement were apparently more likely to have an unfavorable outcome. Lastly, although the influence of ethnic origin is unproven, children living in foreign countries of French overseas territories, but treated in France have an increased risk for unfavorable outcomes. PMID- 1929112 TI - [The treatment of cystinosis with cysteamine]. PMID- 1929113 TI - [Ethical and analytical problems in man and greater mammals]. AB - Toxicomania and doping give rise to an increasing number of drug measurements in the body fluids. Consequently the analysts have to face, at one and the same time, ethical and analytical problems. Should the analyst participate to investigations organised in order to disclose a toxicomania in a working place? The author suggests a positive answer as long as the adduct person benefits to a social and medical care. What is the analytical meaning of a positive test? Taking into account the increasing sensitivity of the methods used, thresholds have to be established, at least for the blood concentrations of the licit drugs, in order to avoid asserving the legality to the sensitivity of the apparatus. PMID- 1929114 TI - [Benzoate determination in medicinal syrups with a PVC membrane ion selective electrode without inner reference solution]. AB - Two electrodes sensitives to benzoate ion, without inner reference solution, in which tetraoctylammonium benzoate in dibutylphtalate (type A) or 2 nitrophenyloctylether (type B) immobilized in PVC are used in membranes, applied on a conductive support, were prepared. The response characteristics and behaviour of this low-cost electrodes are presented. The analytical application possibilities are discussed and shown as practical examples on analyses of the ion in medicals syrups. PMID- 1929115 TI - [Contribution to the pharmacodynamic study of a ketosulphoxide derivative (omega methylsulphinyl alpha-acetothiophene). Activity on the CNS]. AB - In order to establish the pharmacological profile of a series of ketosulphoxide derivatives which have been synthesized in the pharmaceutic and organic chemistry department of the Sevilla Pharmacy Faculty, a study of omega-methylsulphinyl alpha-acetothiophene has been initiated. Experiments were carried out on male Swiss mice, using a dosage of 100 and 200 mg/kg. High toxicity tests have been undertaken, followed by an investigation of activity at CNS levels. The results obtained show that the composite mentioned has a marked depressant activity lacking in any significant toxic effects. PMID- 1929116 TI - [Some aspects of the management of house-hold refuse]. AB - Each day the average Frenchman produces near 1 kg of HHR, mainly paper and cardboard, vegetal and animal putrescible residues, glass, plastics, metals, ashes,... giving four important linked fractions of recyclable, biodegradable, combustible and inert matters. Production and precollection of HHR are of direct concern for the user, mainly in the collective housing; but the rubbish chute acts as a brake to the selective collection of HHR, which is one aspect of the valorization process of HHR, growing up in France. Three other treatments are used: combustion in plants with or without energy recovery, biological degradation of HHR as a compost used in agriculture, and dumping on or in the ground. All of them have advantages and disadvantages and then they must be used in complement of each other. The treatment units have some pollution effects on the environment and must be watched. Treatment refuses and solid, liquid or gaseous pollutants must be managed as much as HHR themselves. Three examples of collection-treatment-elimination french units are briefly described in Dunkerque (a mean town with selective collection), Bourgneuf-en-Mauges (a rural country with biological treatment and dumping) and Paris (a big town with a new incineration plan). Then the state of the management of HHR in France in 1989 is described with special attention to collection (99.4% of the population), recovery of glass (25%) and paper-cardboard (42%) and authorized treatment (94%) as dumping (43%), incineration (40.5%) and biological (7.5%). Accent is made about the importance of prevention (decrease of refuse production, way of consumption and life style, education of the masses) and of a good management of the HHR and of their treatment refuses and pollutants to limit environmental degradation. PMID- 1929117 TI - [Heptaminol chlorhydrate: new data]. AB - Heptaminol hydrochloride is widely used for the treatment for orthostatic hypotension. It continues to elicit controversy as to its mode of action since Loubatieres (1951) described its powerful inotropic action on an ischaemic preparation. Twenty five years later it has been suggested that this drug exerts its action by interfering with the release and uptake of catecholamines (Grobecker and Grobecker, 1976). The aim of this review was to report new experimental approaches and new data relative to the mode of action of heptaminol hydrochloride. In the rat, heptaminol hydrochloride prevented orthostatic hypotension, and increased the noradrenaline plasma concentration. In bovine chromaffin cells maintained in primary cultures, it was found to be a competitive inhibitor of noradrenaline uptake. This inhibition may partially account for its antihypotensive effect. The cardiotonic effect was studied using 31 P nuclear magnetic resonance spectroscopy and left ventricular pressure measurement in rat isolated hearts. The results suggest that the inotropic effect during moderate ischemia could be related to a restoration of internal pH possibly mediated by a stimulation of the Na+/H+ exchange. The satellite cells of adult skeletal muscles are myogenic cells involved in muscle regeneration. In culture, they differentiate into myotubes and thus mimic some aspects of the in vivo myogenic process. Heptaminol hydrochloride, which did not significantly alter the cloning efficiency or proliferation, increased the capacity of satellite cells to differentiate into myotubes. PMID- 1929118 TI - [Determination of fluorides and fluorophosphates in drugs, toothpastes and mineral waters by gas liquid chromatography]. AB - Fluorides and monofluorophosphates present in drugs, toothpastes and mineral waters are converted into an organic compound by trimethylchlorosilane at acidic pH. The trimethylfluorosilane formed is determined with isopentane as internal standard by gas liquid chromatography with flame ionization detection. Some drugs containing fluoride at therapeutic or physiologic concentrations also some toothpastes and mineral waters were analyzed easily by this method. No interferences due to excipients or to other active substances present in drugs or toothpastes were observed with this method. Because of its sensitivity (0.01 ppm), its accuracy (CV: 0.7 a 2%) and its simplicity, the chromatographic method proposed is suitable for the routine controls of fluorides in drugs, toothpastes and mineral waters. PMID- 1929119 TI - [Tension activity of pulmonary surfactant: adsorption of liposomes of model phospholipids]. AB - One peculiarity of pulmonary surfactant, which is the tensioactive material physiologically present at the surface of alveoli, lies in its very quick localization at in the air-water interface. This being one of the limiting factors of artificial exogenous surfactants for the treatment of patients suffering of respiratory distress syndromes, we have studied the mechanisms which are intervening in the adsorption kinetics of a pure liquid--phase phospholipid, the dioleylphosphatidylcholine (DOPC), and of mixtures of dipalmitoylphosphatidylcholine (DPPC) and phosphatidic acid (PA) in presence of divalent cations (Ca++ and Mg++). The adsorption kinetics of liposomal suspensions of DOPC, which were studied by the Wilhelmy plate method, are determined by the existence of a barrier potential which height depends on the temperature and medium osmolarity, and on the deformability of vesicules. The study of PA-DPPC liposomes was performed with the help of a pulsating bubble surfactometer, a physicochemical instrumentation which mimics the pulmonary alveoli. To obtain performant responses with this model, high concentrations of PA and of divalent cations Ca++ and Mg++ are needed. These results, which are similar to those observed during the study of liposomal fusion, allow to propose a model, according to which adsorption of liposomes at the air-water interface is comparable to liposomal fusion and may be related to the presence of a thin aqueous film. PMID- 1929120 TI - [Synthesis and antiparasitic activity of various N-acetylacetates of nitrogen heterocycles]. AB - The synthesis and the study of the antiparasitic activity of various heterocyclic N-ethylacetates derived from substituted derivatives of piperazine, benzimidazole and benzotriazole do not show antiparasitic property. A slight activity on Entamoeba histolytica and Trichomonas vaginalis is noted with the nitro derivatives of benzimidazole and benzotriazole. PMID- 1929121 TI - [Immunoelectrophoresis or immunofixation: identification of monoclonal gammopathy]. AB - Both methods enable the clinical laboratory to identify monoclonal gammapathies with a good sensitivity. The immunofixation method, more quickly used than the immunoelectrophoresis, is easier to obtain the best resolution. It is well adjust for the characterization of low concentration gammapathies like immunoglobulin light chains. Immunofixation appears to take a more and more important place in the clinical laboratory. PMID- 1929122 TI - Vicary Lecture, 1989. John Hunter's disciple--Frederic Wood Jones. PMID- 1929123 TI - Risk factors and operative mortality in surgery for colorectal cancer. AB - The operative mortality rate after surgery for colorectal carcinoma remains significant. A series of 578 patients has been studied prospectively. The features which most significantly affect operative mortality are the age of the patient, a history of loss of weight, limited preoperative patient mobility and the presence of intestinal obstruction with perforation of the bowel. By identifying high-risk groups of patients, attention may be focused on particular patients at risk, in order to reduce operative mortality. PMID- 1929124 TI - Surgical simulation for general practitioners. AB - The White Paper (1) and its implementation means that general practitioners will perform many more minor procedures. Training and retraining will be required in the manual skills necessary to handle instruments and remove such conditions as surface lesions. We describe a training aid based on porcine dermis which allows a practitioner the opportunity to acquire such skills. It may also be useful for training paramedical personnel. PMID- 1929125 TI - Teaching aid in skin surgery. PMID- 1929126 TI - Use of a breast template: an aid for orientation of breast biopsy specimens. PMID- 1929127 TI - Evaluation of current surgical management of acute inflammatory diverticular disease. AB - During the period 1980 to 1987, 127 patients were admitted with acute complications of diverticular disease; clinically diagnosed as acute diverticulitis in 86, peritonitis in 33 and colonic obstruction in eight. In those patients diagnosed as acute diverticulitis, conservative treatment was effective in 73 (85%), the other 13 requiring surgery. Of 31 patients, with a clinical diagnosis of peritonitis who underwent operation, 19 (61%) had free purulent or faecal fluid at laparotomy and the remainder had a localised phlegmonous mass. Sigmoid resection was performed in 34 patients and nonexcisional surgery in 18. In the earlier period of the study, there was a preference for the former procedure in patients with peritonitis rather than those with phlegmonous diverticulitis (63% vs 28%), and in the later period of the study, resection was the preferred treatment in both groups (91% vs 93%). The increase in resectional surgery significantly reduced mortality, at completion of treatment, in patients with peritonitis (P less than 0.05) but not in those with phlegmonous diverticulitis. There was an additional benefit of resection in the lower number of procedures per patient (1.5 vs 2.1), a lower median total hospital stay (32 days vs 50.5, P less than 0.01) and a lower wound infection rate (16% vs 32%, P less than 0.01) at the end of treatment. The optimum surgical approach at laparotomy for acutely complicated diverticular disease would therefore appear to be a resectional procedure. Of the patients operated on for 'peritonitis', 39% were found to have a localised diverticular mass/phlegmon. This group of patients, if identified earlier, may respond to conservative management in the first instance, and highlight an area where further improvements in management may be possible. PMID- 1929128 TI - An audit of surgical emergencies in the very old. AB - The surgical emergency admissions of patients over the age of 80 years at the hospitals of the West Berkshire Health Authority during 1989 have been analysed. The results were then compared with those of 1976 and 1966 in an attempt to identify any changing trends. The total number of admissions increased by almost 37% from 248 in 1976 to 339 in 1989. There was a dramatic increase in those patients admitted with gastrointestinal problems. The average length of stay was less in 1989, being 9 days compared with 15 days in 1976; this was despite the fact that the average length of stay for all ages was comparable for the 2 years in question. The overall mortality rate has not appreciably altered being 21.8% in 1976 and 22.4% in 1989. Excluding terminal disease the mortality rates were 12.5% and 15.9% for 1976 and 1989 respectively. Despite the increased numbers of patients admitted the total beds occupied by the over 80s has actually fallen between 1976 and 1989, due to their shorter hospital stay. Figures for the year 2000 predict a continuing increase in the number of elderly patients in the community. It is unlikely that we will be able to reduce hospital stay much further and therefore the total number of beds occupied by the very old in the acute surgical ward will rise steadily. PMID- 1929129 TI - Control of presacral bleeding in rectal surgery. AB - A technique for controlling life-threatening presacral bleeding is described. This consists of a sterilised metallic drawing pin pushed through the synthetic coagulant Surgicel (Johnson and Johnson) directly into the bleeding point in the sacrum. Two patients are described in which this technique was used with a successful outcome. PMID- 1929130 TI - Nasogastric suction after elective abdominal surgery: a randomised study. AB - The value of nasogastric tube decompression after elective abdominal operations was assessed in a randomised trial in which 97 patients were and 100 were not allocated postoperative nasogastric decompression. Only two patients in the latter group subsequently required decompression. There was no statistically significant difference in the incidence of mortality, complications (including vomiting) or time to return of intestinal motility between the two groups. There was a significantly higher incidence of sore throat (P less than 0.0001) and nausea (P less than 0.05) in patients who received nasogastric decompression. A postal questionnaire to 259 UK general surgeons (96% replied) revealed that postoperative nasogastric decompression was usually used by 92% of surgeons after a Polya gastrectomy, 72% after a small bowel anastomosis, 49% after a large bowel anastomosis and 20% after cholecystectomy. We conclude that such a routine is not justified and should be reserved for those patients developing specific complications. PMID- 1929131 TI - Which general surgical operations must be done at night? AB - During the 1980s there has been increasing concern about hospital medical staffing. Achieving a Balance will lead to a reduction in the number of registrars and a possible increase in the work done out-of-hours by consultants. The deleterious effects of long hours of work have also attracted attention and, in particular, there is concern about the safety of operations performed at night by unsupervised junior doctors. There is an urgent need to examine how out-of hours work can be reduced. This study was conducted in two phases. The out-of hours surgical workload in four hospitals was examined. Appropriateness of the procedures and activities being carried out was then considered by a consensus panel, aided by a literature review. Most out-of-hours operations were performed by junior staff. The principal reasons suggested for operating at night are lack of day-time theatre space and the need to gain experience. There was considerable variation in the frequency with which different types of operation were performed among hospitals. The views of the panel suggest that up to one-third of operations currently performed at night could be postponed. It may be possible to postpone a higher proportion of operations performed after midnight. The appropriateness of the remaining operations has major implications for the work of consultants following the implementation of Achieving a Balance. PMID- 1929132 TI - Wound compression pads are of no value after local anaesthetic breast biopsy. AB - In a randomised study of 120 patients undergoing breast biopsy, wound compression pads did not reduce the frequency of postoperative bruising or haematoma formation, and 12% of the 62 patients having pads had complaints regarding their use. Wound compression pads are of no value after local anaesthetic breast biopsy. PMID- 1929133 TI - The trephine colostomy: a permanent left iliac fossa end colostomy without recourse to laparotomy. AB - An operative technique for performing a permanent end sigmoid colostomy without recourse to laparotomy is presented. The results from 16 patients have shown a very low morbidity. The technique was unsuccessful in three patients, each needing a formal laparotomy. PMID- 1929134 TI - Mobile versus fixed site lithotripsy. AB - The efficacy of a mobile Dornier HM4 lithotriptor, was compared with that of a fixed site Siemens Lithostar. A total of 115 calculi in 98 patients were treated, 55 on the mobile Dornier and 60 on the Lithostar. The groups were similar except for stone size, the mean of the Lithostar group being 11 mm compared with 7.7 mm in the Dornier group. Fragmentation rates were not significantly different, 88% and 75% on the mobile and fixed site machines, respectively and, at 3 months follow-up 66% and 46% were stone free or with fragments of less than 2 mm. There were no serious complications, and the incidence of mild complications was similar in the two groups. We conclude that the mobile Dornier HM4 is an effective lithotriptor and can offer several advantages over fixed site machines. PMID- 1929135 TI - Orthopaedic trauma in men: the relative risk among drinkers and the prevalence of problem drinking in male orthopaedic admissions. AB - Admissions to an acute male orthopaedic ward (n = 369) were asked about their accident, their alcohol consumption, and alcohol-related problems in the past 2 years. Comparing their consumption with that of males from a community survey revealed an increased risk of orthopaedic admission in drinkers consuming 21 units of alcohol/week or over, relative to drinkers consuming less than 21 units/week, in the age group 31-50 years. In all, 34% of the sample met a criterion for problem drinking based on self-reported alcohol consumption and/or medical and social problems associated with alcohol. In 13%, alcohol was viewed by the patient as having contributed to the accident, and in 19% according to the interviewer's perception of whom 76% were classifiable as problem drinkers. Twenty-six men said the accident had made them think about changing their drinking habits. Detection of problem drinking in orthopaedic male admissions is possible and could be usefully linked to a counselling service. PMID- 1929136 TI - Urological complications of renal transplantation: the impact of double J ureteric stents. AB - In a 10 year series of 350 consecutive renal transplant operations, the overall urological complication rate was 7.7%. During this period double J stents were introduced and were used either in the treatment of actual urological complications or as a prophylactic measure to protect ureters which had been damaged at retrieval. A total of 34 double J stents were used in 33 patients. The indications were: ureteric obstruction (n = 13), urinary leak (n = 5), short transplant ureter anastomosed using an extravesical ureteroneocystostomy (n = 10) and ureteric injury at the time of organ retrieval (n = 6). Thirty-two double J stents were inserted at open operation and two were inserted by an antegrade method after percutaneous nephrostomy. Improvement in renal function occurred in 16 out of the 18 cases of urological complications. No kidneys were lost and there were no deaths as a direct result of these complications. In a number of cases the insertion of a double J stent was the only treatment, thus eliminating the need for more complex surgery. All 16 patients who had a ureteric stent inserted as a prophylactic measure at the time of transplantation made uncomplicated postoperative recoveries. Urinary tract infection was relatively common (27%) after double J stent insertion, but other complications were rare. In conclusion, double J stents have proved to be a useful adjunct in the management of renal transplant related urological complications. PMID- 1929137 TI - Development of thrombophlebitis in peripheral veins with Vialon and PTFE-Teflon cannulas: a double-blind, randomised, controlled trial. AB - A series of 54 normal subjects were randomised to have either a Vialon or a PTFE Teflon peripheral vein cannula inserted in a vein in each forearm to observe the development of thrombophlebitis. Cannulas were inspected twice daily for up to 5 days to observe the development of three signs, erythema, oedema or hardness and one symptom, pain. Each sign and symptom was recorded twice daily at three points, the cannula insertion site, the mid-point of the cannula and the cannula tip. The degree of change was recorded as less than 1, 1-2 and greater than 2 cm. Any cannula causing any sign greater than 2 cm was removed. By the end of the study over 40% of both types of cannula had been removed. There were no significant differences between the numbers of each type of cannula removed at any time point throughout the duration of the study. There were no significant differences in the amounts of erythema or hardness, but minimally increased swelling was observed at the mid-point of the PTFE-Teflon cannulas (P = 0.022). Despite the theoretical superiority of Vialon as a cannula material, under controlled conditions there appears to be little difference in its inherent capacity to cause the thrombophlebitis. PMID- 1929138 TI - A controlled trial of short-term versus standard axillary drainage after axillary clearance and iridium implant treatment of early breast cancer. AB - A controlled trial has been conducted to determine the safety of early drain removal after axillary clearance as part of conservation treatment in early breast cancer. A total of 84 patients was entered into the study of whom 41 had the drain removed after 5 days, irrespective of the volume of fluid draining, and 43 had drains removed when fluid was less than 20 ml per day. Of the standard drainage group, 28% required percutaneous aspiration of lymph because of subsequent accumulation, compared with 49% of the short-term drainage group. Early drain removal was not associated with any increase in wound complications nor in cosmetic outcome, but did enable earlier discharge of patients from hospital. PMID- 1929139 TI - Assessment of burn injury in the accident and emergency department: a review of 100 referrals to a regional burns unit. AB - Accurate assessment of the extent of thermal injury in the accident and emergency (A&E) department is essential if appropriate resuscitation and referral to a specialist unit is to occur. However, review of 100 referrals to a regional burns unit confirms that assessment is often inaccurate, and usually undertaken by no one more senior than a casualty officer, leading to suboptimal treatment and referral. Severe thermal injury should be assessed by a team of senior doctors, according to the major trauma protocol, and casualty officers should receive better training in the assessment of less extensive burns. PMID- 1929141 TI - Malignant neck lumps: a measured approach. PMID- 1929140 TI - Lymphoscintigraphy in the detection of cervical metastases from oral carcinoma: a pilot study. PMID- 1929142 TI - Amputations in diabetics. PMID- 1929143 TI - Guidelines for surgical audit by computer. PMID- 1929144 TI - General surgery with a special interest in vascular surgery: an audit of relative workload. AB - In a district general hospital (DGH) almost all vascular surgery is provided by general surgeons with a vascular interest and training. There is a growing view, however, that vascular surgeons should be 'pure' to the exclusion of other surgery. In an attempt to define the relationship between general and vascular work in a DGH we have analysed, prospectively, out-patient, in-patient and theatre workload over a three-month period. Eight-hundred-and-forty-four patients (277 new, 567 follow-up) were seen in the clinics. Nine per cent of new vascular referrals and 33 per cent of new general referrals were booked for admission. There were 356 admissions (50 per cent 'emergencies') representing a wide spectrum of general surgery. Elective and emergency vascular cases stayed in hospital for twice and four times longer, respectively, than general patients. Vascular patients represented 26 per cent of the caseload but accounted for 46 per cent of the bed occupancy. Vascular operations made up only 21 per cent of the total theatre caseload (233 procedures) but consumed 34 per cent of theatre time. The vascular unit in a DGH deals with a substantial number and wide variety of general surgical cases. Vascular surgery, however, consumes disproportionately large amounts of out-patient and theatre time and hospital beds. This has implications both for the planning of vascular services and also for the resource allocation within the hospital. PMID- 1929145 TI - Recommended values for use in surgical audit and surgical workload analysis. PMID- 1929146 TI - [MRI in osteoporotic and metastatic vertebral compressions: apropos of 60 cases]. AB - Magnetic resonance imaging (MRI) was performed in 60 patients with vertebral compression fractures caused by either bone metastasis (BM) or osteoporosis (OP). In the BM group (20 patients, 62 BM with 22 compression fractures), the signal was decreased on T1-weighted images in all cases and was usually increased on T2 sequences, in the whole vertebral body or in patchy areas. The vertebral body showed a diffuse posterior bulging in 85% of patients; malignant infiltration often involved pedicles, posterior arch or soft tissues. In the OP group (40 patients, 160 vertebral fractures): a significant recession of one of the corners of the vertebral body, different from metastatic bulging, was observed in 37% of patients; the spinal cord signal depended on the stage: during the first 4 months, the signal was low on T1 and high on T2 sequences, with a characteristic band disposition, which may involve most of the vertebral body even in mild fractures; the modifications extended to the pedicles in 5 cases; after 6 months, the signal was normal. MRI specificity was 92% between malignant versus benign compression fractures. MRI had a better sensitivity than bone scan for depicting vertebral BM. In OP, MRI signal modifications disappeared several months before increased uptake of technetium. This study emphasizes the value of MRI for the diagnosis of osteoporotic versus metastatic vertebral compression fractures when morphological and chronological parameters are added to the signal intensity analysis. PMID- 1929147 TI - [Periprosthetic false aneurysm after Bentall's operation: diagnosis with magnetic resonance imaging]. AB - Periprosthetic false aneurysm due to dehiscence of a suture line represents a serious postoperative complications after Bentall's procedure, because of its asymptomatic presentation and spontaneous course towards progressive increase in size with high risk of sudden rupture. This type of complication justifies systematic radiologic follow-up. Magnetic Resonance Imaging, as proved by our two cases, is a reliable technique in the diagnosis of this complication requiring reoperation. PMID- 1929148 TI - [Pattern of hepatic pathology diagnosed with echography in Yaounde (Cameroon)]. AB - The purpose of our study was to assess the pattern of liver diseases diagnosed by ultrasonography (US) in Yaounde (Cameroon). From a total of 1,007 consecutive US studies performed over a period of 14 months in subjects over the age of 15 years, we found 322 patients with a sonographic diagnosis of liver disease. 8 diagnoses comprised 83% of the patients. Apart from non specific homogeneous hepatomegaly these diagnoses consisted of: cirrhosis, primary liver malignancies, liver abscess, congestive hepatomegaly, secondary liver malignancies, diffuse steatosis and nodular calcifications. 30 liver abscess drainages were performed with sonographic guidance. We conclude that in our environment where Computed Tomography is scarce and expensive, US is a useful tool in the study of some of the most frequent liver diseases. PMID- 1929149 TI - [Echoencephalography in myelomeningocele]. AB - Infants with myelomeningocele very often present cranio-cerebral anomalies such as Arnold Chiari malformation. Cranial ultrasonography allows early evaluation of these malformations and helps to detect complications in surgically treated children. PMID- 1929150 TI - [Abdominal desmoid tumors and Gardner's syndrome. Report of a complete case]. AB - The authors report a case of patient with a complete Gardner's syndrome. This case is characterized by the association of desmoid tumor of the thoraco abdominal wall, mesenteric fibromatosis, gastric and duodenal polyposis and a rectal adenocarcinoma. They present a brief review of the syndrome which raises problems of clinical classification and therapeutic difficulties. PMID- 1929151 TI - [Posterior thoracic spinal tuberculosis: assessment by x-ray computed tomography and magnetic resonance imaging apropos of a case]. AB - A case of tuberculosis of the vertebral arch, with CT and MR studies is presented. A large necrotic paravertebral extension better shown on gadolinium enhanced MR study, may be helpful to suggest the diagnosis which must be confirmed by vertebral biopsy. PMID- 1929152 TI - [Azygos vein injury. A new complication of upper digestive endoscopies]. AB - A patient presented with a ruptured azygos vein following esophagoscopy. The diagnosis was difficult. Selective angiography was helpful and surgical treatment ensured good result. This is the first case of this type to be reported in the literature. PMID- 1929153 TI - [Postoperative iatrogenic coronary-ventricular fistula]. AB - Acquired coronary cardiac fistulas are rare. To date, thirty cases have been published in the literature, all secondary to thoracic trauma. The right cardiac chambers were more frequently involved. A recent continuous cardiac murmur is the most constant finding. Nontreated, these lesions tend to induce coronary insufficiency and congestive heart failure. 22 of the 30 reported cases were managed surgically. We hereby report a case of postoperative coronary cardiac fistula secondary to left ventricular venting, in which the fistula involved the left ventricular cavity. PMID- 1929154 TI - [Giant esophageal fibrovascular polyp. Apropos of a case]. AB - Fibrovascular polyps, together with leiomyomas, constitute the great majority of rare benign tumors of the oesophagus. Their size and their frequently high level of attachment sometimes give them a spectacular clinical presentation. The hazards involved in the interpretation of radiological and endoscopic data account for frequent mistakes in their diagnosis. The determination of the pedicle site defines the choice of the surgical approach. A diagnostic error and the choice of an incorrect approach are the two main causes of therapeutic difficulties. PMID- 1929155 TI - [Jejunogastric intussusception. Apropos of a case]. AB - Jejunogastric intussusception is a rare complication after gastric surgery. The authors report a case of acute jejunogastric intussusception diagnosed in a 57 year-old woman, 22 years after vagotomy and gastroenterostomy for duodenal ulcer. There are three types of jejunogastric intussusception: 1) the acute type, presenting as a surgical emergency, and characterized by a sudden onset of cramp like epigastric pain, followed by nausea and vomiting, with a palpable epigastric mass. 2) the chronic recurrent type, which may progress to the acute type of may result in severe disability, and may require corrective surgery depending on the severity of the symptoms. 3) the acute post-operative type, presenting on the 4th or 5th post-operative day, and usually improving with conservative treatment. PMID- 1929156 TI - [Osteoid osteoma of the lunate. Apropos of a case. Value of x-ray computed tomography]. AB - The authors report a new case of osteoid osteoma of the lunate. The absence of any specific clinical or radiographic features emphasises the importance of computed tomography, which not only confirms the diagnosis, but, more importantly, defines the topography and also guides the surgical approach and even the surgical technique. PMID- 1929157 TI - [Radiological training in the Federal Republic of Germany]. PMID- 1929158 TI - [Ovarian endometriosis]. PMID- 1929159 TI - [Lumbo-aortic lymphadenectomy in ovarian cancers]. AB - Systematic lumbo-aortic lymphadenectomy has revealed the importance of lymphatic dissemination of ovarian cancers: the incidence of lumbo-aortic metastases reported in the literature is high (15 to 25% of so-called early stages, false stage I and II). An exact staging assessment is an essential prognostic factor; underestimation of apparently early stages leads to insufficient treatment, reducing the long-term survival rate. The correlation with intraperitoneal extension, the degree of differentiation and the histological type is only partial. Retroperitoneal lymph node invasion has a prognostic significance at each stage. Lastly, lumbo-aortic lymphadenectomy appears to provide a specific therapeutic benefit as part of maximal tumour reduction surgery. PMID- 1929160 TI - [Cancer of the rectum. Results of a prospective study comparing preoperative rectal touch and transrectal ultrasonography with postoperative histopathology before and after preoperative radiotherapy]. AB - Between January 1988 and December 1990, 23 patients with rectal cancer were evaluated by clinical staging (23) and transrectal sonography before (22, one complete stenosis) and after radiotherapy (21). Two criteria were correlated with histological findings: a) the confinement to the rectal wall or spread beyond and b) the presence of meso-rectal lymph node involvement. The 22 patients who underwent transrectal sonography before radiotherapy were staged as uT2: 3 cases, uT3: 17 cases and uT4:2 cases. Fifteen days after irradiation, transrectal sonography showed a regression on the tumor in all cases; the uT stage was different in 9 patients but there was no change in the uN stage. The comparison of the preoperative clinical and sonographic assessment of local invasion beyond the rectal wall with postoperative histopathology revealed a correlation: a) with digital examination in 13 of the 21 patients with palpable tumors, b) with transrectal sonography before irradiation in 12 of the 22 staged tumors, c) with transrectal sonography after irradiation in 17 of the 21 staged tumors. The presence of meso-rectal lymph node involvement determined by histologic examination was correlated with the results of transrectal sonography for 14 of the 21 staged tumors. Transrectal sonography provides a good assessment of the tumor stage before irradiation. This stage should be considered for the study of survival. PMID- 1929161 TI - ["Pouchitis" after ileo-anal anastomosis with reservoir]. AB - Pouchitis is the most poorly understood complication of ileoanal anastomosis. The incidence reported in the literature ranges from 7 to 42% as there are no diagnostic criteria. The various clinical symptoms and endoscopic findings raise the possibility that pouchitis is a heterogenous disease, in which the role of bacterial overgrowth and recurrence of inflammatory bowel disease must be clarified. PMID- 1929162 TI - [Endoscopic and transhepatic intubation of malignant bile duct strictures for postoperative jaundice]. AB - Out of 625 patients referred for stenting for a malignant stricture of the biliary tract, 97 (15.8%) had undergone previous surgery. Resection had been performed in 43 cases, by-pass in 15, surgical stenting in 11, laparotomy in 28. The stricture was located in the porta hepatis in 48 patients (49.5%) in the middle common bile duct (CBD) in 47 (48.5%) and juxtapapillary in 2 (2%). Endoscopic retrograde transhepatic stenting was successful in 51 patients (52.5%). Percutaneous transhepatic stenting was successful in 41 cases out of 46 (85%) and in 5 cases, only external drainage was possible. A 75% reduction in serum bilirubin was observed in 78 patients (81.5%) and normalization was observed in 66 (90%) who survived more than one month. The complication rate was 31.3% in the endoscopic group and 47.7% in the percutaneous transhepatic group, with a mortality related to early complications of 9.8% and 19.6% respectively. The higher complication rate of transhepatic stenting is at least partially related to an unfavourable selection of patients in this group: failures of endoscopic stenting, high frequency of hilar strictures. The mortality at D 30 was 24%, significantly higher in hilar strictures than in middle CBD strictures (p less than 0.02). A late obstruction of the stent occurred in 43 patients (58%) after an interval of 103 +/- 52 days, and endoscopic retreatment was possible in 65% of cases. The median survival was 153 days in subhilar strictures and 104 days in hilar strictures. These results justify considering the possibility of palliative stenting after failure of a surgical treatment especially in peri ampullary and middle CBD strictures. PMID- 1929163 TI - [Major surgical complications after 73 consecutive liver transplantations]. AB - In order to evaluate the incidence of postoperative surgical complications requiring additional surgery, we report 73 consecutive liver orthotopic transplantations performed in 60 patients from June 1983 through June 1989. Transplantations were performed in 54 adults and 6 children for the following reasons: postnecrotic cirrhosis in 31, biliary diseases in 16, hepatobiliary malignancy in 7; Wilson's diseases in 3 and fulminant hepatitis in 3. Surgical complications requiring additional surgery occurred in 35 (58%) patients with 53 operations. Twenty-two patients (36%) had postoperative bleeding complications, 5 (8%) biliary complications, one had a late artery thrombosis and 16 (26%) had miscellaneous complications. The latter group included 6 abdominal hernias, 3 bowel perforations, 2 bowel obstructions, 2 cases of pneumothorax, 2 cases of chylous ascitis, one liver necrosis, one hepatic artery kinking, one peritonitis and one cardiac tamponade. The incidence of surgical complications was not significantly different in patients who underwent retransplantation as compared to those who had a single transplantation. We did not find a significant difference in surgical complication rate according to the preoperative liver disease. In comparison with the literature, in our series, we had a higher rate of abdominal hernia but a lower rate of biliary complications. PMID- 1929164 TI - [Long-term results of modified supra-pyloric gastrectomy in the treatment of gastric ulcer]. AB - An original technique for supra-pyloric gastrectomy with preservation of sphincter function of the pylorus was performed in a series of 26 patients with benign ulcer of the lesser curvature. The results were evaluated 3-10 years after the operation. Twenty-five patients obtained a satisfactory results (visick grades I or II). The rate of gastric emptying was tested with a meal labelled with TC 99 in 17 patients. Only one patient suffered from gastric stasis. It is concluded that supra-pyloric gastrectomy with preservation of the pylorus has a place in the treatment of benign ulcers of the lesser curvature. PMID- 1929165 TI - [Long-term outcome of surgically treated peptic ulcer. Review of a series of 419 patients operated for peptic ulcer]. AB - The authors report an analysis of 419 cases of operated peptic ulcer. 68.78% of patients had a mean follow-up of 4 years. After clinical and endoscopic examination, the results of the survey were assessed on the basis of various parameters, which demonstrated that the results of surgery were related to socio occupational problems, smoking, the site of the ulcer, the stage, the history of the ulcer prior to the operation, the conditions of the operation and obviously the surgical technique used. PMID- 1929166 TI - [Implantable devices for permanent venous access. A single-center prospective study comparing an AIDS population with a control population (80 cases)]. AB - Although the tolerance of indwelling catheters in AIDS patients has been evaluated, the complications of implanted devices in this population are unknown. This encouraged us to compare in a prospective unicenter trial, dealing with 80 consecutive implanted devices, the complications of this kind of system in 20 AIDS patients, versus a control population. The follow-up was 10,658 days. No patient was excluded or lost to follow-up. In the control population, the infection rate was 5% (0.036 per 100 catheter days). We observed 3 thromboses (5%). In the AIDS group, the infection rate was 25% (0.21 per 100 catheter days). We observed 1 thrombosis (5%). This trial shows that implanted devices are more frequently infected in AIDS patients (p less than 0.05) than in a control population; it suggests that the infection rate in AIDS patients is not superior to the indwelling catheter rate, as reported in the literature. The precision of bacteriological tests and use of antibiotic therapy adapted to the clinical context should help to determine, in the presence of suspected infection, whether the implanted device can be maintained or should be removed in this high risk population. PMID- 1929167 TI - [Totally implantable venous access sites. Results of a series of 101 cases]. AB - The authors report their results of the use of 101 totally implanted venous access systems for chemotherapy in 92 patients. They stress the high incidence (19.8%) of complications: thrombosis 6.8% and 6.9% linked to the material. The correct complication rate must be decreased by strict attention paid to the surgical procedure, use and greater education of the nursing staff. The value of this material is to give greater comfort to patients and to assess its widespread use for intensive long-term chemotherapy. PMID- 1929168 TI - [Prevention of postoperative wound dehiscence. Comparative study of polyglactin 910 mesh and total reinforced extraperitoneal sutures]. AB - Postoperative wound dehiscence is a serious complication. Various surgical procedures have been proposed to prevent it but only few studies have compared their effectiveness. The authors report a retrospective study on 292 high risk patients operated between 1980 and 1988. These patients were divided in two groups according to the methods of abdominal wall support: 226 patients (group I) with total reinforced extraperitoneal sutures and 66 (group II) with a polyglactin 910 mesh. Preoperative risk factors, surgical pathology and the incisions performed were similar in the two groups. Only two parameters were different: the number of previous operations and emergency surgery which were more frequent in group II (p less than 0.05). Fourteen patients in group I developed postoperative wound dehiscence and none in group II (p = 0.02). Nine of these patients were reoperated with a mortality of 28.5%. The frequency of the other complications was similar in the two groups. Polyglactin 910 mesh was more effective than total reinforced extraperitoneal sutures in the prevention of post operative wound dehiscence justifying its use in high risk patients. PMID- 1929169 TI - Clinical research and the marks of a good research worker. PMID- 1929170 TI - Assessment of ventricular septal defect by colour flow mapping. AB - The purpose of this study was to evaluate the usefulness of colour flow mapping (CFM) in the diagnosis and classification of congenital ventricular septal defect (VSD) and in the confirmation of spontaneous and surgical closure. Between August 1988 and March 1990, a total of 102 patients with isolated VSD (82 preoperative and 20 postoperative), age ranging from one day to 14 years, were subjected to 176 echocardiographic examinations. Sequential cross sectional imaging and CFM were the main modalities of assessment with conventional Doppler interrogation for quantitative measurements. In the preoperative group, there were 56 (68.3%) perimembranous (pm) VSD, 14 (17.1%) muscular (m) VSD and 12 (14.6%) doubly committed subarterial (dcsa) VSD. Ventricular septal defect was detected by CFM only in 88.9% of m/VSD, 57.6% of dcsa/VSD and 11.8% of pm/VSD (p less than 0.01). Spontaneous closure rate was highest in m/VSD (28.6%) followed by pm/VSD (8.9%) (p = 0.05). None of the dcsa/VSD closed as assessed by CFM. In the postoperative group, CFM served to quickly confirm complete closure without residual left to right shunt in 20 patients. In addition, CFM was useful in the assessment of haemodynamics and flow directed Doppler interrogation. Hence, CFM is a useful adjunct to cross sectional imaging in the assessment of children with isolated VSD. PMID- 1929171 TI - The elderly reach independence through a community stroke rehabilitation programme. AB - Cerebrovascular disease resulting in stroke had shown a rising trend in the last decade among the elderly population in Singapore. To prevent dependency states, a home stroke rehabilitation programme was implemented in 1988 with the help of staff nurses trained to provide rehabilitation for stroke patients at home. These nurses were specially trained by experienced physiotherapists. A simple format was used to identify patients with good rehabilitation potential, while they were in the acute hospitals. The 244 stroke patients were studied by their age, sex, the status of motivation to go through rehabilitation and the level of family support. Out of the 224, 139 patients who had good and fair rehabilitation potential were referred to the Senior Citizens' Health Care Centres (SCHCCs) directly, as they already had sitting and standing balance. Twenty-two patients with poor rehabilitation potential were provided home nursing care. The rest of 83 patients with good and fair rehabilitation potential needed home rehabilitation before being referred to the SCHCC, as they had no sitting and standing balance. These 83 patients followed-up at home, were studied by their age, sex, rehabilitation potential, family support, number of nurse home visits and duration of rehabilitation required to gain independence in mobility. By 12 weeks, 84% of the patients improved in their goals towards independence irrespective of age. Marked improvement were shown in all the ten areas studied namely concentration, head control, return of tone, sitting balance, standing balance, mobility, power of upper and lower limbs, co-ordination and continence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929172 TI - Recognition of pernicious syndromes in malaria infections. AB - The case records of 64 patients with malaria over a five year period admitted to the University Hospital, Kuala Lumpur were examined. There were 32 cases of P. falciparum, 26 cases of P. vivax and two cases of mixed infections. Four cases of P. malariae were recorded. The clinical findings, biochemical and haematological parameters were examined for any indication of a pernicious syndrome. A high index of suspicion of a malarial infection may be based on the findings of anaemia, thrombocytopaenia, hyponatraemia, renal failure and abnormal liver function tests in the face of a negative blood film. These pernicious syndromes occur more often in malignant tertian malaria (anaemia 50%, hyponatraemia 39.1%) but a high percentage of the other malarial species show these abnormalities (P. vivax anaemia 57.7%, hyponatraemia 19.2%). When these abnormalities are present but blood films for malaria parasites are negative, repeat blood films are warranted until a parasitological diagnosis is achieved and correct treatment may be started. PMID- 1929173 TI - Acute renal failure prognostic indices in hospital inpatients referred for haemodialysis. AB - Forty-eight patients with acute renal failure (ARF) who were referred to the Department of Renal Medicine, Singapore General Hospital for acute dialysis between August 1985 and August 1989 were studied retrospectively to identify risk factors associated with ARF that serve as prognostic indicators. There was no difference in the mean age of survivors and non-survivors (49.5 +/- 17.5 years vs 53.5 +/- 18 years, p greater than 0.05). The overall mortality rate was 52%. ARF as a result of surgical complication had a higher mortality rate in comparison to ARF from medical complications (66% vs 50%, p greater than 0.05). Septicaemia was the most common cause of ARF requiring dialysis. Hepatobiliary sepsis was the most frequent cause of septicaemia. Pre-dialysis serum urea and creatinine levels, and the number of dialysis treatments did not affect the outcome. Poor prognostic indicators included oliguria or anuria, fluid overload and coma. Patients tended to have a worse outcome if they had more than three risk factors taken from the following list:-decreased renal perfusion, assisted ventilation, coma, gastrointestinal dysfunction, recent surgery, sepsis, congestive heart failure, hepatobiliary dysfunction, malignancy, diabetes mellitus, chronic renal insufficiency and poor nutritional status. Early referral of patients with septicaemia due in particular to hepatobiliary infection may improve the prognosis. PMID- 1929174 TI - Vesicoureteric reflux and renal scarring in children--a local perspective. AB - This study was undertaken to determine the extent of primary vesicoureteric reflux and renal scarring in patients investigated for urinary tract infection in the Singapore General Hospital between 1983 and 1988. The clinical profile of patients and possible clinical features associated with renal scarring were analysed. These findings serve as a useful guide in the investigation and management of VUR in our population. The incidence of vesicoureteric reflux among patients investigated for documented urinary tract infection was high at 32.9%. The mean age at presentation was 15.2 months. Almost all patients were less than five years-old. A male predominance was noted in affected infants. High grade refluxes of Grade IV or more (International Reflux Study Classification) were found in 45.7/patients and were associated with a higher incidence of recurrent urinary tract infection (p less than 0.05). Thirty-four 99mTc-dimercaptosuccinic acid scans were done and 46.4% of refluxing kidneys showed renal scars. The incidence of renal scarring was significantly higher in patients presenting at an early age (less than 2 years), in high grade reflux and in recurrent urinary tract infection (p less than 0.05; p less than 0.01 and p less than 0.001 respectively). Therefore all children with documented urinary tract infection who are less than five years old and especially male infants should be fully investigated for early detection and treatment of vesicoureteric reflux and renal scars. Kidneys with vesicoureteric reflux at risk of scarring appeared to be those with early presentation, high grade reflux and recurrent urinary tract infection whose management should therefore be vigorous. PMID- 1929175 TI - Health screening for the elderly--the Singapore Senior Citizens' Health Care Centres' experience 1986-1989: an overview. AB - A systematic health screening programme for the elderly aged 55 years and above was implemented in the first Senior Citizens' Health Care Centre (SCHCC) in 1986. This programme was expanded to two more SCHCCs by 1989. The first 1,224 clients aged 55 years and above, who attended this programme in the first three SCHCCs were studied in this paper. The characteristics of the elderly who voluntarily attended the SCHCCs for health screening were studied with respect to their referrals, socio demographic status, whether they had regular physician care, the existing medical problems and the new medical problems picked up at health screening. Of those screened, 49.6% were referred for the programme by relatives and self, and 28.2% by community centres, thus, showing that community and family supported the programme. Only 7.2% of referrals to the screening programme came from general practitioners and 4% from polyclinic doctors. It is interesting to note that 40% of clients had no regular physician care. About two thirds (57.2%) had one or more existing chronic medical conditions or disability at the time of screening. The majority with existing conditions had hypertension (24.8%) and diabetes (15.5%). Other existing conditions were ischaemic heart disease (6.2%), cataract (3.9%) and asthma (3.6%). The pick-up rate of medical conditions among the clients at the time of health screening was 38.6% for the whole group. This showed a rising trend from the younger to the older age groups being 29.4% in the age group 55 to 64, to 45.8% in the age group 65 to 74, and 51.4% in the age group 75 years and above (p less than 0.001). Some of the topical issues related to a health screening programme for the elderly have been discussed. PMID- 1929176 TI - Prevention of heat disorders in the Singapore Armed Forces--1984-1989. AB - A review of the incidence of heat disorders in the Singapore Armed Forces was done in relation to the preventive and corrective measures applied. Data was compiled and analysed from records kept by the SAF Medical Services. A thorough review was made into all the preventive measures carried out thus far and the effectiveness was evaluated. There was a rise in the incidence of heat strokes from eight cases in 1984 to a peak of 46 cases in 1986. Subsequently, aggressive measures were adopted and the incidence fell significantly in 1988 and 1989. The main strategy involved a comprehensive health education programme, regulations, active surveillance and aggressive treatment. However, the incidence has not fallen to the pre-1984 levels. Therefore, a strict vigilance must be constantly maintained to prevent further mortality and morbidity. PMID- 1929177 TI - Causes for infertility: a comparative study. AB - A representative group of 204 infertile couples from Kuala Lumpur, Malaysia were compared to a similar group of 633 couples from Aberdeen, UK in an attempt to study if there was any regional difference in the pattern of infertility seen. The protocol for investigation and diagnostic criteria for both centres were standardised. A significant difference (X2 = 63.43; p less than 0.001) was seen. The reasons for these differences are discussed. PMID- 1929178 TI - Immunophenotypic characterisation of monocytoid differentiation markers in acute non-lymphoblastic leukaemias. AB - The FAB classification of acute non-lymphoblastic leukaemias has been shown to have some clinical use in the prognostication of patient survival. ANLL with monocytoid features (M4, M5) fare worse than those which are predominantly myeloblastic (M1, M2). Classification is, however, sometimes difficult if non specific esterase activity is not strongly expressed. Monoclonal antibody characterisation of myeloid differentiation antigens may be of some use as a supplementary aid. We immunophenotyped the blast cells from 26 cases for HLA-Dr, CD14 (Mo2, My4), CD13 (My17) and CD33 (My9) expression using the APAAP method. A combination of CD14 and CD33 used together was useful in differentiating myeloblastic from monocytoid acute non-lymphoblastic leukaemias. We conclude that the use of surface markers is a useful adjunct to the diagnostic means presently available. PMID- 1929179 TI - Stereochemistry in therapeutics--knowing what the left hand is doing. AB - Many drugs have asymmetrical molecules and, therefore, can exist as enantiomeric forms. Although it is relatively difficult to distinguish these enantiomers from each other, enantiomers of the same drug can possess very different pharmacological attributes. Failure to consider the stereochemical properties of these drugs may lead to erroneous conclusions about drug effects. The clinical use of pure enantiomers may be associated with improvement in efficacy and lower toxicity of the drug. However, this may be a costly exercise. It is nevertheless, important for the clinician to be aware of these issues so that there may be optimal use of these drugs. PMID- 1929180 TI - Human immunodeficiency virus infection in Singapore--containment strategies. AB - The worldwide occurrence of the Acquired Immunodeficiency Syndrome (AIDS) since its advent in the United States in 1981 has resulted in a global dilemma on how best to reduce transmission of the Human Immunodeficiency Virus (HIV). In Singapore, a national AIDS programme was established in 1985 to control the spread of the disease in the country. The programme included health care delivery, education of health care workers and the community, surveillance and counselling of individuals with high risk behaviours, as well as protection of the nation's blood supply. This paper examines the global response to the HIV pandemic and containment strategies appropriate to Singapore based on established epidemiological data. PMID- 1929181 TI - Drug therapy of the fetus and neonate. AB - The fetus and neonate are very sensitive and delicate. Events occurring during this period can therefore, have a very significant influence on later life. Drugs given to the pregnant women may have a significant impact on the fetus, as the thalidomide disaster has shown. Drug therapy of the fetus via the mother has also been proven to be effective in certain situations, especially with regard to improving lung maturity. With advances in visualisation of the fetus by ultrasonography, direct fetal treatment has been successfully performed. The neonate immediately after delivery is in a very precarious state, especially if premature. Drug therapy is sometimes indicated then to ensure his well-being. Such drug therapy will have to take into consideration absorption problems in relation to a prolonged gastrointestinal transit time as well as hepatic and renal immaturity, together with a relatively greater volume of distribution of the drug (Vd). When these considerations are taken into account, effective therapy can be instituted with successful results. Drug treatment for specific conditions in the premature baby, when tailored to their needs and limitations, have indeed been successful. PMID- 1929182 TI - A review of 58 patients in Singapore with significantly high anti-Toxoplasma serotitres. AB - Over a 42-month period, 58 patients presenting at the Singapore General Hospital were identified to have IgG anti-Toxoplasma serotitres of 1:1024 or higher by the indirect immunofluorescence test. This retrospective study examines the clinical presentation and management of these 58 patients. About 60% of these 58 patients had presented with lymphadenopathy, 20% with ocular symptoms and 14% with bad obstetric history. Almost all patients with IgG anti-Toxoplasma serotitres exceeding 1:1024 had presented with lymphadenopathy (with a modal titre of 1:4096). In contrast, most of the patients who presented with ocular symptoms or bad obstetric history had lower modal titres. The majority of patients who had presented with lymphadenopathy were Chinese, aged 21 to 35. Typically, they presented with a painless, mobile, solitary cervical node of three to four weeks duration as the only symptom, had biopsies where the histopathology was suggestive of toxoplasmosis, received no treatment and experienced no sequelae. The study concludes that: acute toxoplasmosis is common in Singapore and presents typically as asymptomatic cervical lymphadenopathy in a young Chinese; the incidence of congenital infection is also believed to be high, based on the number of cases presenting with fetal wastage and the prevalence of ocular toxoplasmosis; pigs in Singapore may constitute an important reservoir for the transmission of this disease to man. PMID- 1929183 TI - Cytotoxic chemotherapy for gynaecologic malignancies. AB - Cytotoxic chemotherapy is assuming an increasingly important role in the management of gynaecologic tumours both in an adjuvant setting and as therapy for clinical disease as well as for palliation. Choriocarcinoma and germ cell tumours of the ovary which in the prechemotherapy era were nearly always fatal, are now among the most curable of all cancers; significant prolongation and improvement in quality of life for those with epithelial ovarian carcinomas and uterine malignancies is now possible. Clinical pharmacological principles in gynaecological anticancer chemotherapy, such as those concerned with selection of appropriate agents, factors in the decision to treat, response evaluation and the rationale for combination chemotherapy are discussed. Combination regimens exploit understanding of cellular genetics, different biochemical mechanisms of drug action and differing toxicity profiles both to minimise emergence of drug resistance and to obtain enhanced efficacy. Common and frequent toxic effects encountered with chemotherapeutic agents used in gynaecologic oncology chemotherapy are presented and their management, which includes strategies to minimise occurrence or reduce their severity is outlined. PMID- 1929184 TI - Chondrosarcoma of the spine--report of two cases. AB - Chondrosarcoma arising from the spine is a rare malignant tumour, associated with a poor outlook due to inadequate excision in the majority of the cases. We report two cases arising from the cervical and the thoracic spine. Both survived 15 and eight years respectively. This condition carries with it a grave prognosis because of its proximity to the vital structures, making complete extirpation of the tumour frequently difficult if not impossible. Recent developments and progress in adjuvant radiation therapy has improved the prognosis significantly. PMID- 1929185 TI - Prognostic usefulness of cytogenetic analysis for haematological malignancies- two case reports on acute myeloid leukaemia. AB - Since the setup of marrow cytogenetic analysis at the National University Hospital (NUH) of Singapore in 1988, we have systematically examined all patients with haematological neoplasia for clonal abnormalities. In most patients, diagnosis was unequivocal on clinical and morphological grounds so that karyotyping was undertaken for prognostic purposes. Two patients are described who illustrate the prognostic implications of nonrandom chromosomal derangements. They highlight the increasing appreciation of the importance of cytogenetic analysis as an independent and reliable prognostic tool in the management of haematological malignancies. PMID- 1929186 TI - Schistosomiasis in Singapore--a case report. AB - Schistosomiasis although endemic in the Far East, has not been reported in Singapore. We describe an 83 year-old lady with Schistosoma japonicum infection presenting with bloody diarrhoea. We discuss its diagnosis and postulate the mode of transmission of this infection in urban Singapore. PMID- 1929187 TI - HIV infection and Pneumocystis carinii pneumonia--bronchoscopic diagnosis in two patients. AB - Pneumocystis carinii pneumonia is extremely common in patients with the acquired immunodeficiency syndrome (AIDS). Diagnostic techniques vary between different institutions depending on availability of expertise. We have limited experience in the workup and evaluation of patients with human immunodeficiency virus infection because we have at present only 56 reported cases of HIV positive individuals. We report here two cases where Pneumocystis carinii pneumonia was the index illness and the diagnosis was confirmed by bronchoscopy. PMID- 1929188 TI - Occupational asthma due to ethylene diamine. AB - We report a case of bronchial asthma due to ethylene diamine in a chemical worker. The typical relationship with work exposure was elicited from the occupational history and serial peak flow measurements. A late dual asthmatic reaction was seen in bronchial provocation test with ethylene diamine. Bronchial hyper-responsiveness to isopropyly alcohol and histamine was observed and was likely to be the result rather than a predisposing factor for the development of occupational asthma. Amines are a powerful group of small molecular weight asthmatogens that are commonly used in various types of industries locally and should be recognised in the clinical evaluation of workers with asthma. PMID- 1929189 TI - Acute cyclosporin A induced nephrotoxicity in renal allografts. AB - Immunosuppression with Cyclosporin A has resulted in dramatic improvements in the results of cadaveric kidney transplantation in Singapore. However, its major limitation is its nephrotoxicity which can appear in various forms after transplantation including a delay in graft function and chronic renal dysfunction. The clinical course of two patients with initial function but delayed onset of acute functional Cyclosporine nephrotoxicity are described. Recovery was documented in both cases with reduction of Cyclosporine dosage. A decline in renal blood flow and increase in renal vascular resistance is likely to have played a role in the pathogenesis of the acute functional nephrotoxicity. Cyclosporine induced imbalance in Prostaglandin synthesis within the kidney has been implicated. PMID- 1929190 TI - Reversible pure red cell aplasia associated with diphenylhydantoin therapy. AB - Pure red cell aplasia (PRCA) is characterised by an anaemia with reticulocytopenia but with normal leukocyte and platelet counts, and a bone marrow with the selective absence of erythroid precursor cells. Drug-induced PRCA is a rare cause of secondary erythroid aplasia, but distinct from the primary and most secondary forms, it is usually acute and fully reversible upon withdrawal of the causative drug. We report a 36 year-old Chinese man who developed diphenylhydantoin associated PRCA two months after commencing the treatment. Reappearance of reticulocytes was observed six days following the cessation of diphenylhydantoin therapy and the haemoglobin level rose to normal one month later. The extreme rarity of this adverse reaction to a drug used so widely strongly suggests an individual predisposition. PMID- 1929191 TI - Obstructed obturator hernia in 90 year olds--a management dilemma. AB - We present two 90 year-old women with small bowel obstruction from obturator hernias. A higher incidence of such obstruction has been reported in Chinese and the diagnosis should be suspected in elderly women with no previous surgery presenting with small bowel obstruction. Although the diagnosis was suspected in both cases, early surgical intervention was prevented by the patients' and relatives' fears of incomplete recovery with poor quality of life in advanced age. In such situations, we suggest on observation period of not more than two days, and if the general health does not deteriorate significantly, surgery should again be strongly advised. PMID- 1929192 TI - [Pseudo-hyperkalemia. Apropos of a familial case]. AB - One case of pseudo-hyperkalaemia is reported in a women who suffered of labile hypertension and was previously treated by fluorohydrocortisone because of hyperkalaemia. Clinical examination and ECG were normal. An incubation test performed at different temperatures confirmed the diagnosis. There was no haematological abnormality. Familial screening prompted us to discover 2 affected subjects among four studied, according to autosomal dominant inheritance. This abnormality was due to increased passive membrane permeability to potassium at low temperature out of any hematological syndrome. The diagnostic is important to avoid inappropriate medications. PMID- 1929193 TI - [Chronic autoimmune thyroiditis and C-cell hyperplasia. Study of calcitonin secretion in 24 patients]. AB - Serum calcitonin (CT) was determined by radioimmunoassay, using two monoclonal antisera, in 22 women and two men, who had Hashimoto's thyroiditis as confirmed by echographic, immunological or cytological criteria; in 23 patients, serum CT levels were measured after intravenous infusion of pentagastrin (Pg). In 21 cases, basal and Pg stimulated serum CT concentrations were normal. A 61-year-old woman and a 63-year-old man, both euthyroid, had high serum basal CT: 12 pg/ml and 35 pg/ml; infusion of Pg resulted in abnormal increases in serum CT levels: respectively 64 pg/ml and 115 pg/ml. Another patient, a 65-year-old woman with primary hypothyroidism had high serum basal CT: 90 pg/ml (the Pg stimulation test was not done because of ischemic heart disease). Each of these 3 patients had a total thyroidectomy. Pathological examination of the thyroid showed typical features of Hashimoto's thyroiditis and extensive C-cell hyperplasia. After surgery, serum CT levels fell to normal. Therefore, a high serum CT can be observed as the consequence of C-cell hyperplasia in Hashimoto's thyroiditis. PMID- 1929194 TI - [Isolated osteoporosis in a case with Cushing's disease: development after treatment]. AB - The unusual case of a 37 year old woman with Cushing's disease in whom the only feature of hypercortisolism was a clinically asymptomatic osteoporosis is presented. After successful treatment of the disease, serial bone biopsy examinations and bone mineral density measurements (BMD) were performed up to 31 months. 27 months after cessation of hypercortisolism, BMD remained unchanged and histomorphometric examination showed no improvement of the osteopenia in addition to focal osteomalacia. Despite 5 months of calcium and vitamin D therapy, BMD did not improve. This case report emphasizes the importance of routine evaluation of adrenal function in unexplained isolated osteoporosis. Long-term follow-up studies, leaded in a large number of patients are necessary to elucidate the course of osteoporosis in Cushing's syndrome and the usefulness of a specific treatment. PMID- 1929195 TI - [Induction of ovulation by pulsatile gonadoliberin administration. Indications and limits]. AB - With its simplicity, innocuity and efficacy, pulsatile GnRH administration constitutes a considerable advance in ovulation induction techniques. Its purpose is not to replace classic methods like Clomiphene Citrate, gonadotropins or dopaminergic agonists, but to complement them. While the choice of administration route, IV vs SC is still controversial, the efficacy depends mainly on the selection of the patients susceptible of benefiting from this therapy. Low gonadotropic activity hypothalamic amenorrhea remains the best indication for pulsatile GnRH, as substantiated by the results published over the last 10 years. The other anovulation causes, including PCO-S, are more disputable indications, and prospective studies involving homogeneous populations are necessary to assess the true standing of GnRH in such indications. PMID- 1929196 TI - [Diagnostic and therapeutic problems of aorto-enteric fistulas caused by aortic prostheses. 5 surgical cases of which 4 were successful]. AB - The clinical characteristics, surgical treatment and therapeutic results, were surveyed in 5 cases of aorto-enteric fistulas observed in 650 abdominal aortic reconstructive operations in ten years. The fistula concerned the duodenum in two cases, the jejunum in one and the ileum in two cases. Two patients were treated by removal of the prosthesis and an axillofemoral bypass, one by an axillofemoral shunt only and the two others by repair of the graft. One patient died a few days after the operation, another eighteen months later. The prognosis of aorto enteric fistulas after aortic reconstructive surgery is often bleak. It should be improved by an early diagnosis, supported by anamnestic history and an upper endoscopy. An aggressive surgery, whose modalities are discussed, gives maximum chances of success. PMID- 1929197 TI - [Percutaneous alcoholization of the celiac plexus under echographic guidance: an alternative to splanchnicectomy? Study of 21 cases]. AB - Celiac plexus block is usually performed under fluoroscopic or tomodensitometric guidance. We report on a new procedure using sonographic guidance. The patient lies in supine position. We use a real-time sonograph (Kontron Sigma 1 AC) with a 3.5 MHz probe. On a transverse plane, the celiac axis is localized emerging from aorta. After local anesthesia, the tip of the spinal needle (177 mm, 22 G) is placed close to aorta (about 5 mm) on both sides. 10 to 15 ml of 1 per cent lidocaine then 10 to 15 ml of absolute alcohol are injected on each side. 21 patients (10 males, 11 females, mean age: 61) underwent the procedure. They presented with cancer of the pancreas in 14 cases, metastatic nodes in 3 cases, cholangiocarcinoma in 2 cases and chronic calcifying pancreatitis (CCP) in 2 cases. No pain relief occurred in 3 patients (14 per cent). On of those presented with CCP but the endoscopic cystic diversion of a small cyst was successful to eradicate pain. Partial pain relief occurred in 5 cases (24 per cent). Total pain relief was obtained in 13 cases (62 per cent). No complication related to the treatment was observed. Sonography is a simple and safe method of guidance to perform alcohol block of the celiac plexus. The anterior approach may prevent neurologic complications related to other methods of guidance. PMID- 1929198 TI - [A rare cause of upper digestive tract hemorrhage: an esophageal fistula in mediastinal tuberculous adenopathy]. AB - We report a case of esophageal fistula of a tubercular mediastinal adenopathy revealed by melena and which was diagnosed partly by means of endoscopy and partly by scanning after carrying out endoscopic fistulography. Endoscopic ultrasound, which was carried out as a complementary examination, confirmed this diagnosis. PMID- 1929199 TI - [Value of omeprazole in the treatment of collagenous colitis]. AB - The authors report the case of a patient suffering from collagen colitis in whom the administration of omeprazole achieved the rapid and total abolition of the clinical signs and a significant reduction of the collagen band (measurements determined over 10 cryptic spaces using a graduated micrometric ocular microscope). Although the outcome of this disorder is variable, with the possibility of spontaneous recovery or, more frequently, of remission, the authors consider, in their conclusions, that omeprazole may have a beneficial effect in this disorder even though the mechanism for this has not been established. PMID- 1929200 TI - [Association of autoimmune thrombopenia with cancer of the pancreas. A case report]. AB - The authors report a case of immune thrombopenia preceding a pancreatic cancer. The clinical and biological findings do not permit the diagnosis of para neoplastic syndrome, but permit the hypothesis of immunological disorders associated with cancers. PMID- 1929201 TI - [Lymphocytic gastritis. Anatomo-clinical study]. PMID- 1929202 TI - [Ulcerous disease of endocrinal origin caused by a non-gastric substance]. AB - The purpose of this paper is to report on a form of duodenal ulceration associated with a major hypersecretion that we described in 1984. This entity belongs to the group of endocrine duodenal ulcer diatheses of which the Zollinger Ellison Syndrome (ZES) is the prototype. We have recently in 1989 reported a series of patients with clinical and pathologic features indistinguishable from those of the Zollinger-Ellison syndrome but without hypergastrinemia. We have also found that the plasma and the tumor tissues of these patients contains a potent non-gastrin secretagogue. PMID- 1929203 TI - [Gastroduodenal reflux and non-ulcerous dyspepsia. Is it an accidental association?]. PMID- 1929204 TI - The continuing challenge of primary brain tumor management: the contribution of positron emission tomography. PMID- 1929205 TI - Identification of early recurrence of primary central nervous system tumors by [18F]fluorodeoxyglucose positron emission tomography. AB - As aggressive neurosurgery and adjuvant therapy have become standard care for most patients with primary central nervous system (CNS) tumors, limitations of posttreatment neuroimaging techniques have become more apparent. Interpretation of computed cranial tomography (CT) and magnetic resonance imaging (MRI) in patients with brain tumors is complicated by changes related to surgery, corticosteroids, radiation, and chemotherapy. We investigated the role of 18F-2 fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (FDG-PET) in these difficult diagnostic situations by obtaining FDG-PET scans in 5 patients following temporal lobectomy for epilepsy, in 5 patients with recurrent anaplastic gliomas before and after corticosteroid therapy, and in 5 patients after the development of histologically confirmed radionecrosis. We also obtained postoperative FDG-PET scans in 32 consecutive patients undergoing initial resection of a primary brain tumor. Our results indicate that glucose uptake as detected by FDG-PET scanning with [18F]fluorodeoxyglucose is not increased in the postoperative period; is not affected by steroid therapy; and accurately predicts early recurrence of tumor, supplementing other predictors of tumor behavior, including extent of resection, histological diagnosis, and postoperative CT. Thus PET using [18F]fluorodeoxyglucose can contribute to the optimum management of patients with primary brain tumors. PMID- 1929206 TI - Antiepileptogenic effects of conventional anticonvulsants in the kindling model of epilespy. AB - We sought to determine whether the clinically effective anticonvulsant drug valproate exhibited antiepileptogenic properties in the kindling model (we use the term anticonvulsant to mean suppression of seizure, and antiepileptogenic to mean suppression of development of epilepsy). We compared and contrasted valproate with two other anticonvulsant drugs, phenobarbital and carbamazepine. We investigated the effects of these drugs on the development of kindling, that is, the number of stimulation-induced afterdischarges required to induce enhanced seizure susceptibility in rats. Valproate exhibited powerful antiepileptogenic effects as evident in a dose-dependent increase in the number of afterdischarges required to induce kindling. These effects were not due to retained valproate or an active metabolite merely masking the expression of kindled seizures. By contrast, carbamazepine was devoid of any antiepieptogenic effects despite exhibiting marked anticonvulsant effects. Like valproate, phenobarbital exhibited both antiepileptogenic and anticonvulsant properties, but its antiepileptogenic properties were significantly less pronounced. The antiepileptogenic effects of valproate and phenobarbital strengthen the candidacy of these agents for the clinical studies needed to investigate pharmacological prevention of the development of epilepsy in high-risk groups. PMID- 1929207 TI - Mitochondrial DNA deletions in inherited recurrent myoglobinuria. AB - We describe two brothers with inherited recurrent exertional myoglobinuria and alcohol intolerance associated with distinct morphological abnormalities of muscle mitochondria and multiple deletions of muscle mitochondrial DNA. Patient 1 (26 years old) and Patient 2 (21 years old) had recurrent episodes of myoglobinuria provoked by strenuous exercise or alcohol intake, from the age of 18 years. Although their serum lactate and pyruvate levels were normal at rest, they were significantly elevated by aerobic exercise. Histochemistry of their biopsied limb muscles showed ragged-red fibers and cytochrome c oxidase-negative fibers as well as degenerating and regenerating fibers. Electron microscopy showed pronounced accumulation of abnormal mitochondria containing paracrystalline inclusions and moderate increases of glycogen particles. The enzyme activities of the electron-transfer complexes in the isolated muscle mitochondria of Patient 2 were within normal ranges. Southern blot analysis revealed multiple deletions of mitochondrial DNA, some of which were common between the patients. Polymerase chain reaction of their muscle mitochondrial DNA detected multiple abnormal fragments indicating mitochondrial DNA deletions. We propose that a defect of the mitochondrial energy-transducing system due to multiple mitochondrial DNA deletions is a novel genetic cause of inherited recurrent myoglobinuria. PMID- 1929208 TI - Change in pattern of muscle activity following botulinum toxin injections for torticollis. AB - Twenty patients with torticollis had electromyographic studies of their neck muscles performed before and after a series of local injections of botulinum toxin. The pattern of muscle activity changed after the injections, and this effect persisted even after head position had returned to baseline. Patients who did not experience any clinical benefit from the injections also demonstrated a change in the pattern of muscle activity. These results suggest that the underlying abnormality in torticollis usually involves a general motor program for head position, rather than the activity of individual neck muscles. PMID- 1929209 TI - BN rats do not reject F344 brain allografts even after systemic sensitization. AB - Embryonic brain tissue allografts under many circumstances survive transplantation into the brain. It is generally believed that such grafts will not survive if the host animal is systemically sensitized, by skin grafting or other means, to major histocompatibility complex (MHC) antigens of the donor animal. We have found that F344 brain grafts survive in BN hosts even when the host is systemically sensitized to F344 tissue. Embryonic cerebral neocortex from F344 donors was transplanted into BN host rats (n = 95). Subsequently, the host rats were systemically sensitized with donor skin (n = 25), brain tissue (n = 41), or spleen cells (n = 6) and compared with a control group of rats consisting of allografts with no sensitization or sham procedures (n = 23). Rejection of the transplants in BN rat hosts was not provoked by any of the sensitization methods tested. Minor immunological responses that did not result in rejection were, however, present in many host animals. We did not observe infiltration of W3/13+ T cells and OX8+ cytotoxic lymphocytes in any of the groups. Nevertheless, substantial infiltrations of OX6+ antigen-presenting cells and W3/25+ helper T cells were present. There was also an extensive enhancement of MHC class I immunoreactivity in parts of the grafted tissue developing within the third ventricle, but not for the same type of graft in the lateral ventricle. This increase of MHC class I expression was not accompanied by infiltration of cytotoxic T cells. Our findings thus suggest that neural graft rejection depends on general genetic susceptibility to immune reactions, particularly experimental allergic encephalomyelitis and not only on disparity between donor and host antigens encoded by the MHC. Moreover, enhancement of MHC class I and class II expression within transplanted tissue does not predict graft rejection. PMID- 1929210 TI - Late onset dementia with argyrophilic grains and subcortical tangles or atypical progressive supranuclear palsy? AB - Most clinically demented elderly patients are found at autopsy to have Alzheimer's disease, multi-infarct dementia, Parkinson's disease, Pick's disease, or Creutzfeldt-Jakob disease. We studied 5 patients clinically characterized by late onset dementia whose brains showed no pathological evidence of Alzheimer's disease, or any other specific neuropathological diagnosis. We found argyrophilic grains, coiled bodies, abundant Alz-50-positive and thioflavine S-negative neurofibrillary tangles, and neuropil threads in the hippocampus, entorhinal cortex, locus ceruleus, substantia nigra, subthalamic nucleus, and inferior olives. Ultrastructurally, the grains, threads, and tangles were composed of straight tubulofilamentous structures, 25 nm in diameter, similar to those found in patients with progressive supranuclear palsy but different from the paired helical filaments of patients with Alzheimer's disease. These findings suggest that the late onset dementia with argyrophilic grains syndrome is also characterized by the presence of tangles and threads with the topographical distribution of progressive supranuclear palsy. PMID- 1929211 TI - Percutaneous electrical stimulation of corticospinal pathways at the level of the pyramidal decussation in humans. AB - Stimulation over the base of the skull can activate descending motor pathways to produce electromyographic (EMG) responses in muscles of the arm and leg. The evoked EMG responses were larger when the muscles were preactivated by a small voluntary contraction compared to when they were completely relaxed. The latency of these responses in preactivated muscles was approximately midway between that produced by electrical stimulation over the motor cortex, and by electrical stimulation over the cervical enlargements. With horizontally spaced electrodes, the latency difference between cortical and brainstem stimulation was 1.8 milliseconds in all muscles tested. The latency difference between cervical and brainstem stimulation was 3.9 milliseconds for the first dorsal interosseous and 2.6 milliseconds for tibialis anterior muscles. These values suggest that brainstem stimulation occurs at the level of the cervicomedullary junction. With vertically spaced electrodes in the midline, stimulation often occurs at a higher level. The EMG responses from brainstem stimulation differed from those following cortical stimulation in two ways: (1) They were simpler in form, and (2) their onset latency was the same in active as it was in relaxed muscles. This suggests that brainstem stimulation evoked a large descending motor volley in comparison with the multiple volleys that cortical stimulation can produce. Collision experiments between cortical and brainstem volleys indicated that the major part of the responses evoked by brainstem stimulation were conducted via the large diameter component of the corticospinal tract. PMID- 1929212 TI - In vivo magnetic resonance spectroscopy of brain and muscle in a type of mitochondrial encephalomyopathy (MERRF). AB - Phosphorus magnetic resonance spectroscopy allows noninvasive measurement of the intracellular phosphate-containing metabolites and intracellular pH in localized volumes of human muscle and brain in vivo. This technique was used to study 8 patients with a mitochondrial cytopathy (myoclonus epilepsy with ragged red fibers). Phosphorus magnetic resonance spectroscopy of resting gastrocnemius muscle demonstrated significantly increased relative intracellular inorganic phosphate concentrations (p less than 0.0005) and decreased phosphocreatine to inorganic phosphate concentration ratios (p less than 0.01) in the patients, although only 3 had myopathic signs or symptoms. We propose, therefore, that phosphorus magnetic resonance spectroscopy of resting skeletal muscle is a useful clinical test in evaluation of progressive myoclonus epilepsy. In contrast to results from muscle, however, the relative phosphate metabolite concentrations and intracellular pH in central volumes of the brains of these patients were normal, despite evidence from our previous positron emission tomography studies suggesting that there is diffuse impairment of cerebral oxidative metabolism. PMID- 1929213 TI - Magnetic resonance imaging of Creutzfeldt-Jacob disease. AB - We report a biopsy-diagnosed patient with Creutzfeldt-Jacob disease showing on magnetic resonance images bilateral increased signal intensity in the basal ganglia on long repetition time images. Creutzfeldt-Jacob disease (CJD) is a degenerative process of the brain, induced by a novel infectious agent, and is usually characterized by a rapidly progressive dementia. We report a biopsy diagnosed patient with CJD with a distinctive magnetic resonance (MR) appearance. PMID- 1929214 TI - Attention modulates somatosensory cerebral blood flow response to vibrotactile stimulation as measured by positron emission tomography. AB - In human primary somatosensory cortex, the cerebral blood flow response to vibrotactile stimulation of the fingers (110 Hz), as measured by positron emission tomography and H2(15)O, was 13% higher (p less than 0.025) when the subjects attended to the stimulus, compared to when they were simultaneously engaged in a distraction task. This suggests that the physiological response of a primary cortical area can be modulated by the attentive behavior of the subject. PMID- 1929215 TI - Selective impairment of smooth-pursuit eye movements due to an ischemic lesion of the basal pons. AB - Voluntary and reflex-like eye movements were measured in a patient with an ischemic lesion of the right basal pons. Ipsilateral smooth-pursuit eye movements were predominantly impaired and interrupted by saccades. This profound smooth pursuit deficit contrasted with only minor abnormalities of visually guided saccades and the vestibulo-ocular reflex. A selective disturbance of smooth pursuit eye movements due to a lesion of the basal pons in this patient concurs with recent work in monkeys suggesting that smooth-pursuit eye movements are mediated by a parietooccipito-ponto-cerebellar pathway. PMID- 1929216 TI - Cranial neuropathy associated with primary amyloidosis. AB - We report 6 patients for whom cranial neuropathy was a major manifestation of primary amyloidosis. In 3 of the 6, multiple cranial nerves were involved. All had tissue biopsy documentation of amyloidosis. In 2, nerve biopsy also confirmed amyloidosis. All had renal involvement manifested by proteinuria. Primary systemic amyloidosis must be considered in the differential diagnosis of cranial neuropathy, especially when proteinuria is present. PMID- 1929217 TI - Sjogren's syndrome and multiple sclerosis. PMID- 1929218 TI - MELAS: a family with paternal inheritance. PMID- 1929219 TI - Pertussis immunization and the central nervous system. Ad Hoc Committee for the Child Neurology Society Consensus Statement on Pertussis Immunization and the Central Nervous System. PMID- 1929220 TI - Adrenoleukodystrophy: a correlation between saturated very long-chain fatty acids in mononuclear cells and phenotype. AB - Saturated very long-chain fatty acids in erythrocyte membranes, blood plasma, and mononuclear cells were studied in 4 patients with childhood-adolescent adrenoleukodystrophy and 4 patients with adult adrenoleukodystrophy and 19 normal control subjects by using high-performance liquid chromatography. Ratios of C26:0 to C22:0 in mononuclear cells, erythrocyte membranes, and blood plasma in patients with childhood-adolescent and adult adrenoleukodystrophy were significantly higher than in normal control subjects. Furthermore, ratios of C26:0 to C22:0 in mononuclear cells were significantly higher in patients with childhood-adolescent adrenoleukodystrophy than in patients with adult adrenoleukodystrophy, whereas there was no significant difference in the ratios in erythrocyte membranes and blood plasma between the two groups of patients with adrenoleukodystrophy. These results suggest that there is a correlation between phenotype and ratio of C26:0 to C22:0 within mononuclear cells in patients with adrenoleukodystrophy. PMID- 1929221 TI - Treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulin. AB - Chronic inflammatory demyelinating polyneuropathy is an immune-mediated demyelinating peripheral neuropathy usually treated with immunosuppressants. We reviewed our experience treating 15 patients (9 men, 6 women) with intravenous immunoglobulin. Six patients were on other therapies at the time of intravenous immunoglobulin infusions (4, prednisone; 2, prednisone and azathioprine). The dose of intravenous immunoglobulin was either 0.3 or 0.4 gm/kg/day for 4 to 5 days. Transient fever occurred in 1 patient. Subjective improvement in sensory symptoms was reported by almost all patients. Objective improvements in strength or functional tasks occurred in only 3 patients, a man with human immunodeficiency virus infection, a 14-year-old girl, and a woman with an immunoglobulin G kappa paraprotein. Our results suggest that individual patients may respond to intravenous immunoglobulin therapy. A multicenter controlled trial is needed to assess properly the role of intravenous immunoglobulin therapy in patients with chronic inflammatory demyelinating polyneuropathy. PMID- 1929223 TI - Follow-up of intractable seizures in childhood. PMID- 1929222 TI - Use of computed tomography, magnetic resonance imaging, and localized 1H magnetic resonance spectroscopy in Canavan's disease: a case report. AB - The neuroradiological evaluation of Canavan's disease in a 38-month-old girl is discussed. Computed tomography showed diffuse symmetrical low attenuation values of the subcortical and deep cerebral white matter. Magnetic resonance imaging demonstrated symmetrical diffuse low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. With the use of 1H magnetic resonance spectroscopy, we were able to show elevated levels of N-acetylaspartic acid in the occipital lobe of our patient. The in vivo measurement of N acetylaspartic acid in the brain by 1H magnetic resonance spectroscopy offers an additional noninvasive diagnostic test for establishing the diagnosis of Canavan's disease. With the increasing availability of magnetic resonance spectroscopy, clinicians may be able to confirm the diagnosis of Canavan's disease immediately after magnetic resonance imaging reveals the typical abnormalities of the white matter. PMID- 1929224 TI - Radiation therapy for brain tumors. PMID- 1929225 TI - Double infarction in one cerebral hemisphere. AB - Thirty-two patients whose first stroke was due to double infarct in one cerebral hemisphere were identified among 1,911 consecutive patients from the Lausanne Stroke Registry. The double infarct involved territories of the superficial middle cerebral artery, superficial posterior cerebral artery, lenticulostriate, anterior choroidal artery, or borderzone. The most common combination involved territories of the anterior middle cerebral artery plus the posterior middle cerebral artery. In the patients with the double infarct, the prevalence of potential cardiac sources of embolism (19%) was similar to that found in the registry in general, but the double infarct was closely associated with tight (greater than or equal to 90% of the lumen diameter) stenosis or occlusion (75%) of the internal carotid artery. The most common neurological picture mimicked large infarction in the middle cerebral artery territory, but nearly half of the patients with double infarct in one cerebral hemisphere had a specific clinical syndrome, which was not found in the 1,879 remaining patients from the registry, including hemianopia-hemiplegia (in 6), acute conduction aphasia-hemiparesis (in 2), and acute transcortical mixed aphasia (in 6), in relation to characteristic combinations of infarcts. These unique clinical and etiological correlates warrant the recognition of double infarct in one cerebral hemisphere from other acute ischemic strokes. PMID- 1929226 TI - Magnetic resonance imaging-based volume studies in temporal lobe epilepsy: pathological correlations. AB - We performed a prospective study correlating magnetic resonance imaging volume measurements of the hippocampal formation with histopathology in 24 patients with intractable partial epilepsy who subsequently underwent an anterior temporal lobectomy for their seizure disorder. Patients with mass lesions verified pathologically were excluded from this study. In 71% of patients, quantitative hippocampal formation atrophy correctly lateralized the temporal lobe of seizure origin; in 29%, the volume study was indeterminant. The severity of the pathological alterations in the hippocampus correlated with the hippocampal formation volume determination. Mesial temporal sclerosis was identified in the surgically excised temporal lobe in 15 patients. The magnetic resonance imaging volume studies indicated hippocampal atrophy in the temporal lobe resected in 14 of the 15 patients. Magnetic resonance imaging-based volume measurements of the hippocampal formation increase the diagnostic yield of magnetic resonance imaging scanning in patients with intractable partial epilepsy related to mesial temporal sclerosis. PMID- 1929227 TI - Epileptiform electroencephalographic abnormalities in liver transplant recipients. AB - We retrospectively studied patients who had undergone orthotopic liver transplantation and who also had electroencephalography to determine whether epileptiform changes were associated with a poor neurological outcome. Study groups were 36 patients who died after transplantation (141 electroencephalograms) and underwent neuropathological examination, 11 who died (18 electroencephalograms) but did not have autopsy, and a third group of 34 (62 electroencephalograms) who remained alive. Epileptiform activity was seen in electroencephalograms of 14 of the patients who died (11 from the autopsy group) and in 2 of those who remained alive. All had multiple epileptiform abnormalities and clinical or subclinical seizures. The incidence of epileptiform activity after orthotopic liver transplantation was fivefold higher in the nonsurvivors. Serious cerebral structural changes were found in 10 of the 11 patients who underwent autopsy. Epileptiform activity in the electroencephalograms of patients who had undergone orthotopic liver transplantation indicates a poor prognosis. It should alert the clinician to investigate further for potentially treatable causes. PMID- 1929228 TI - Serum interleukin-2 concentrations in Guillain-Barre syndrome and chronic idiopathic demyelinating polyradiculoneuropathy: comparison with other neurological diseases of presumed immunopathogenesis. AB - Serum concentrations of the cytokine interleukin-2 (IL-2) were quantitated by enzyme-linked immunosorbent assay in 42 patients with Guillain-Barre syndrome, 15 patients with chronic idiopathic demyelinating polyradiculoneuropathy, 37 patients with other neuropathies, 54 patients with other noninflammatory, nondemyelinating neurological disorders, and 26 healthy control subjects. We found markedly increased serum levels of IL-2 in patients with Guillain-Barre syndrome and to a much lesser extent, in patients with chronic idiopathic demyelinating polyradiculoneuropathy. Increased serum concentrations of IL-2 in patients with Guillain-Barre syndrome returned to normal in parallel with recovery from the disease. These findings suggest ongoing T-cell proliferation in patients with Guillain-Barre syndrome and some patients with chronic idiopathic demyelinating polyradiculoneuropathy. IL-2 levels were also raised in patients with active multiple sclerosis, myasthenia gravis, and herpes simplex encephalitis, and some patients with polymyositis, invoking T cells in the pathogenesis of these diseases. PMID- 1929230 TI - Auditory evoked magnetic fields after ischemic brain lesions. AB - Auditory evoked magnetic fields to noise/square-wave sequences, presented once every 2.2 seconds, were recorded in 8 patients who had ischemic lesions in the auditory cortex or in its vicinity. In 2 patients with large temporoparietal lesions, the magnetic 100-msec deflection (N100m) was absent over the damaged side. In 1 patient with a large but less deep frontotemporal lesion, a small N100m could be discerned on the defective side. Frontal lesions or small lesions in the vicinity of the supratemporal plane had no effect on N100m. Auditory evoked magnetic field recordings may be useful in clinical studies of auditory cortical functions. PMID- 1929229 TI - Focal capsular vascular lesions can selectively deafferent the prerolandic or the parietal cortex: somatosensory evoked potentials evidence. AB - Four patients with a unilateral focal vascular accident involving the internal capsule (but not the cortex) were studied electrophysiologically. Averaged somatosensory evoked potentials (SEPs) to electrical stimulation of the median nerve on the left or the right side were analyzed. In the 3 patients with hemiparesis and normal somatic sensation, the precentral P22 and N30 SEP components were lost, whereas the parietal components were preserved. In another patient with clinical somatosensory loss unaccompanied by any central motor impairment, the precentral SEP components were preserved, whereas the parietal SEP components were lost. Thus, a small capsular lesion can eliminate distinct cortical SEP components by selectively involving either the axons of the thalamic VPLc nucleus going to parietal receiving cortex or the axons of thalamic VPLo going to motor area 4. These findings extend to subcortical lesions the diagnostic value of SEPs in patients with dissociated clinical motor and sensory signs. PMID- 1929231 TI - Short-latency autogenic inhibition in patients with Parkinsonian rigidity. AB - The spinal Ib interneuron efficacy has been compared in 11 control subjects and 19 patients with parkinsonian rigidity. In normal subjects, gastrocnemius medialis nerve stimulation induces an inhibition of the soleus H reflex for 3 to 8 msec with a peak at 5 msec of 83.72 +/- 7.28% of the control value of H reflex. In parkinsonian patients, inhibition is reduced or even replaced by facilitation, which also peaks at 5 msec. The departures from normal values correlate with rigidity intensity assessed by the Webster scale. Increase in rigidity is associated, first, with a reduction of inhibition and, from a score of 2 or more, with facilitation replacing the normal inhibition. In addition to providing an electrophysiological index of rigidity, reduction in autogenic inhibition might be one of the neurophysiological mechanisms underlying rigidity. In association with the known hyperactivity of the Ia inhibitory interneuron in Parkinson's disease, reduction of activity of Ib interneuron could be explained by an increased activity in the reticularis gigantocellularis nucleus; its efferent tracts both inhibit Ib interneurons and activate Ia interneurons. PMID- 1929232 TI - The treatable dementia of Sjogren's syndrome. AB - Progressive dementia developed during a 15-month period in a 56-year-old woman with serologically and clinically documented primary Sjogren's syndrome. Findings from magnetic resonance imaging and angiography were normal, but a brain biopsy disclosed perivascular lymphocytic inflammation in leptomeningeal and parenchymal vessels. Treatment with high-dose corticosteroids produced rapid and nearly complete resolution of the dementia. PMID- 1929233 TI - Theoretic diversity: evolving paradigmatic issues in research and practice. AB - Although research and practice differ in that one is the building of knowledge and the other the application of that knowledge, it is suggested herein that there are interesting parallels to explore between the evolving debate on research methods and the emerging theoretic debates on practice. On the basis of the Canadian experience and the trend toward adoption of a single-theory approach, the authors argue for theoretic diversity in nursing practice settings. PMID- 1929234 TI - Nursing: a practical science of caring. AB - Knowledge development related to caring is examined from the epistemological perspective of nursing as a practical science. Four stages of knowledge development for a practical science of caring are proposed and then used as a basis for evaluating efforts to develop a body of knowledge related to caring. Issues that need to be addressed to facilitate the advancement of nursing as a practical science of caring are identified. PMID- 1929235 TI - Rethinking the environment as a domain of nursing knowledge. AB - Nurses frequently care for individuals whose problems originate from the environment. Yet the environmental paradigm in nursing is client-oriented and psychosocial and does not adequately explain these conditions. Nursing theory and research in the environmental domain are explored in this article and found to be focused within this limited paradigm. Models and theories from other disciplines and upstream nursing approaches that address multidimensional environmental characteristics are discussed in terms of providing direction for making a paradigm shift leading to a revolution in nursing's environmental consciousness. PMID- 1929236 TI - Theory-testing research: building the science. AB - Lack of emphasis on the empirical validation of nursing models has hindered the development of nursing science. This article explores issues concerning theory development in nursing and criteria for evaluating theory-testing research. From a comprehensive review of the literature on theory testing, 15 criteria are identified as essential for evaluating theory-testing studies. The criteria are applied to selected research reports, and recommendations for future use of criteria are suggested. PMID- 1929237 TI - Empathy as an ethical and philosophical basis for nursing. AB - This article reconstructs the concept of empathy. Current conceptualizations in nursing, psychology, and lay usage and philosophic approaches are examined. Factors of empathetic situations are defined. Key issues of the object, moral implications, and the locus of empathy are discussed using illustrations from fictional and professional literature. In the proposed concept, a common humanity is the object of empathy, and the empathetic process occurs within individuals. Ability to empathize varies with the broadness of the base with which each individual is able to perceive the common humanity within another. Moral implications include a duty to base actions in empathy. PMID- 1929238 TI - Nursing science: basic, applied, or practical? Implications for the art of nursing. AB - Nursing has long been described as both a science and an art. If the science of nursing is to be relevant to the art of nursing, then it must be conceptualized and pursued such that these two central components of nursing remain connected. Current conceptualizations of nursing science are examined in terms of the consequences that each conceptualization might have for the art of nursing. Pursuing nursing science as a basic science or an applied science disarticulates the science of nursing and the art of nursing. The author concludes that only if nursing science is conceptualized and pursued as a practical science will the science of nursing be consistently relevant to the art of nursing. PMID- 1929239 TI - A theory of mastery. AB - Mastery is a human response to difficult or stressful circumstances in which competency, control, and dominion have been gained over the experience of stress. The goal of the theory of mastery is to explain how individuals who experience illness or other stressful health conditions may emerge, not demoralized and vulnerable, but healthy and possibly stronger. The human response to stress is fundamentally an existential problem. As such, the theory of mastery has philosophic as well as conceptual roots. PMID- 1929240 TI - Genotypic approach to the study of bacterial resistance to antibiotics. PMID- 1929241 TI - Single-dose pharmacokinetics and tolerance of a cholesteryl sulfate complex of amphotericin B administered to healthy volunteers. AB - Twenty-three healthy volunteer subjects received a single dose of amphotericin B colloidal dispersion or placebo (4:2) in a double-blind, randomized, dose escalating design. Doses ranged from 0.25 to 1.5 mg/kg of body weight. The medication was administered via intravenous infusion at a rate of 0.5 mg/kg/h. Plasma amphotericin B concentrations increased with increasing doses, resulting in a linear increase in the amphotericin B area under the curve. Concentrations in plasma decreased rapidly upon discontinuation of the infusion, indicating rapid tissue distribution. A log-linear biexponential elimination phase was observed. A three-compartment open model was used to describe the distribution and elimination of amphotericin B. The mean terminal elimination half-life ranged from 86 h at the 0.25-mg/kg dose level to 244 and 235 h at the 1.0- and 1.5-mg/kg dose levels, respectively. Mean total body clearance ranged from 219 to 284 ml/kg/h. The volume of distribution increased with dose, from 3.37 liter/kg at the 0.25-mg/kg dose to 7.92 liter/kg at the 1.5-mg/kg dose. At the lowest dose level, 0.25 mg/kg, the medication was generally well tolerated. Progressive increases in the dose led to increasing side effects. At the 1.5-mg/kg dose level, 50% of the patients on active medication experienced nausea, vomiting, and chills. Physical examinations, ophthalmologic examinations, and clinical laboratory parameters remained within normal limits compared with those obtained during prestudy examinations. PMID- 1929242 TI - Pharmacokinetics of carumonam (AMA-1080) in patients with impaired renal function and in those undergoing hemodialysis. AB - The pharmacokinetics of carumonam (AMA-1080) were studied after a single intravenous 1.0-g dose was given to 26 subjects grouped according to their renal functions. Creatinine clearance (CLCR) was above 85, 50 to 84, 10 to 49, and below 10 ml/min/1.73 m2 in groups 1, 2, 3, and 4, respectively. All of the six patients in groups 4 were receiving maintenance hemodialysis, and they were studied both during and between hemodialysis sessions. Carumonam obeyed two compartment model kinetics in all four group. The volume of distribution based on the area under serum concentration-time curve (Varea) did not differ significantly among the four groups, the mean value being 0.309 +/- 0.084 liter/kg. The elimination-phase (beta) half-lives were 1.53 +/- 0.36, 2.00 +/- 0.64, 5.08 +/- 1.85, and 12.8 +/- 4.1 h in groups 1, 2, 3, and 4, respectively. The 0- to 24-h cumulative urinary recoveries of carumonam were 83 +/- 11, 76 +/- 20, 58 +/- 25, and 12 +/- 9% of the administered dose in groups 1, 2, 3, and 4, respectively. The systemic and the renal clearances of carumonam decreased according to the severity of renal dysfunction, and the nonrenal clearance, which was calculated as the difference between renal and systemic clearances also decreased as CLCR decreased. A significant positive correlation existed between beta and CLCR (r = 0.847, P less than 0.01), and the beta of carumonam could be predicted by the following equation: beta (h-1) = 0.00460 X CLCR (ml/min/1.73 m2) + 0.049. Hemodialysis shortened the elimination-phase half-lives from 12.8 +/- 4.1 to 2.66 +/- 1.49 h in the six subjects in group 4. A 5-h hemodialysis in a hypothetical anephric subject weighing 60 kg was estimated to remove 51.4% of the drug present in the body at the start of hemodialysis. PMID- 1929243 TI - Three-dimensional analysis of the synergistic cytotoxicity of ganciclovir and zidovudine. AB - The combined cytotoxicity of zidovudine and ganciclovir in three cell lines of human origin was examined. The data were generated by a new rapid cell proliferation assay and a more sensitive plating efficiency assay. A three dimensional analytical approach was used to evaluate the drug-drug interactions, and the results were compared with those obtained by two conventional methods of analysis. Synergistic cytotoxicity was observed in all cell lines examined and by both assays. Moreover, this synergistic cytotoxicity was statistically significant at physiologically relevant concentrations. It is not known whether these drug-drug interactions manifest themselves in vivo as granulocytopenia or other untoward side effects. These results, however, indicate that further investigation is warranted and that the coadministration of zidovudine and ganciclovir may be contraindicated. PMID- 1929244 TI - Application of mathematical model to multiple-dose experimental chemotherapy for fatal murine pneumonia. AB - Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered for 7 days to mice with pneumonia caused by Klebsiella pneumoniae by using dosage regimens that would simulate multiple dosing in usual clinical treatments at dosing intervals of 8 or 12 h. Viable numbers of the bacteria in the lungs were measured at 12- or 24-h intervals. The mathematical model established in a previous single-dose study was applied in this study to explain the time courses of the changes in bacterial count over 7 days. However, because the error in viable count measurements was larger than that in the previous study, the time course of the changes in mean viable count was not regular and the viable count reduction rate changed during multiple dosing, and therefore it was difficult to explain the time course by repeated application of the mathematical model described previously. This study suggests that the changes in pharmacokinetic and pharmacodynamic parameters during multiple dosing need to be considered. PMID- 1929245 TI - Evidence that amikacin ototoxicity is related to total perilymph area under the concentration-time curve regardless of concentration. AB - Previous studies have failed to fully establish whether ototoxicity is related in any way to the levels of an aminoglycoside antibiotic in the perilymph. To study this we exposed guinea pigs to continuously infused amikacin at four different dosing rates under conditions parallel to those used in our previous study which related ototoxicity to total plasma area under the concentration-time curve regardless of the level in plasma. It was found that at all dosing rates, levels in the perilymph and ratios of levels in perilymph/plasma remained constant as the dosing duration increased from nonototoxic to strongly ototoxic. Plasma and perilymph amikacin levels were found to be linear functions of the dosing rate even at ototoxic dosing exposures, and ratios of levels in perilymph/plasma did not differ between dosing rates. The total perilymph area under the concentration time curve was not different between dosing rates either for a total dose associated with threshold ototoxicity or for one associated with severe ototoxicity. The results suggest that amikacin ototoxicity is related to the integral of the concentration in the perilymph over the total time of amikacin exposure regardless of the level in the perilymph. PMID- 1929246 TI - Antimicrobial susceptibility and molecular epidemiology of beta-lactamase producing, aminoglycoside-resistant isolates of Enterococcus faecalis. AB - beta-Lactamase-producing (BL+), aminoglycoside-resistant (AR) Enterococcus faecalis is endemic in our hospital, having caused widespread colonization and infection. Suitable therapy for infections caused by these organisms has been problematic. We compared the antimicrobial and bactericidal activities, by broth macrodilution and time-kill methods, of several antibiotics, alone and in combination, against BL+, AR isolates of E. faecalis and determined the transmissibility of antibiotic resistance markers. Ampicillin-sulbactam, imipenem, daptomycin, and ciprofloxacin were the most active antibiotics with MICs for 90% of isolates tested of 2, 1, 2, and 1 microgram/ml, respectively, against inocula of 10(3) and 10(5) CFU/ml. Little inoculum effect was noted with imipenem, vancomycin, daptomycin, or ciprofloxacin, while the addition of sulbactam to ampicillin partially inhibited the effect of the increased inoculum. Penicillin-sulbactam and ampicillin-sulbactam combinations in a 2:1 ratio were most frequently bactericidal (greater than or equal to 3-log10-unit decrease in bacterial titers at 24 h for 13 of 20 isolates), followed by daptomycin (8 of 20 isolates) and ciprofloxacin (2 of 20 isolates). Bactericidal activity was not demonstrated for imipenem or teicoplanin. beta-Lactamase production and aminoglycoside resistance were associated with a 60- to 65-MDa plasmid which was easily transferred to a plasmid-free E. faecalis recipient. The 840-bp beta lactamase gene probe hybridized to purified plasmid DNA from BL+ donor isolates of E. faecalis and transconjugants but not from BL- isolates. Ampicillin sulbactam and daptomycin (an investigational antibiotic) seem to be reasonable choices for the empiric therapy of presumed enterococcal infections in hospitals in which BL+, AR E. faecalis strains are isolated. Their use should ideally be supported by tests for bactericidal activity. PMID- 1929247 TI - Effects of amoxicillin-clavulanate combination on the motility of the small intestine in human beings. AB - The amoxicillin-clavulanate combination (Augmentin) frequently induces gastric complaints and diarrhea by an unknown mechanism. The aim of this study was to assess the effects of two orally therapeutic regimens of amoxicillin-clavulanate on small bowel motility in human beings. Duodeno-jejunal manometric recordings were performed in six healthy subjects treated in a cross-over double-blind study with placebo; amoxicillin-clavulanate, 1 g plus 250 mg per os every 12 h for 3 days; or amoxicillin-clavulanate, 1 g plus 250 mg per os every 12 h on day 3 only (1-day regimen). Recordings were all performed on day 3 during a diurnal fasting period, a fed state after a standard dinner, and a nocturnal fasting period. Amoxicillin-clavulanate did not affect the motility of the small intestine during the diurnal fast or the fed state. During the nocturnal fast, amoxicillin clavulanate significantly increased the motility index of the nonpropagated contractions and tended to increase the duration and the amplitude of the propagated contractions. The same digestive motor effect was already observed on the first day of treatment (1-day regimen). This study demonstrates that the oral administration of a therapeutic regimen of amoxicillin-clavulanate is associated, in most cases, with the occurrence of small intestinal motor disturbances. PMID- 1929248 TI - Association of two resistance mechanisms in a clinical isolate of Enterobacter cloacae with high-level resistance to imipenem. AB - Carbapenem resistance was studied in a clinical isolate of Enterobacter cloacae, strain 201 (MIC of imipenem and meropenem, 16 micrograms/ml). This strain was analyzed comparatively with the carbapenem-susceptible parent strain 200, an equally susceptible revertant, 201-Rev, and in vitro-selected mutants with different levels of carbapenem resistance. All strains produced similarly high amounts of the same cephalosporinase (pIapp = 8.8). Strain 201 apparently lacked two major outer membrane proteins of ca. 37 and 38 kDa, while 201-Rev produced only the 37-kDa protein. The permeability coefficient, determined with cephaloridine, was reduced up to ninefold in the resistant strains which also showed a substantial reduction in the uptake of [14C]meropenem. The introduction of the plasmid-borne ampD gene (whose product decreases the expression of ampC) resulted in almost complete cessation of cephalosporinase production in all strains and a substantial decrease in the MICs of the carbapenems which remained, however, 8- to 16-fold higher than those determined for the susceptible strains containing the ampD gene. This "residual" resistance was attributed to reduced outer membrane permeability. The contribution of cephalosporinase production was verified in a reverse experiment, in which the introduction of ampC into a low level cephalosporinase producer resulted in a fourfold increase in the carbapenem MICs. From these results, we infer that reduced outer membrane permeability and high-level cephalosporinase production can operate in conjunction in clinical isolates of E. cloacae to confer imipenem resistance. PMID- 1929249 TI - Structure-activity relationships of pentamidine analogs against Giardia lamblia and correlation of antigiardial activity with DNA-binding affinity. AB - 1,5-Di(4-amidinophenoxy)pentane (pentamidine) and 38 analogs of pentamidine were screened for in vitro activity against the enteric protozoan Giardia lamblia WB (ATCC 30957). All compounds were active against G. lamblia as measured by a [methyl-3H]thymidine incorporation assay. Antigiardial activity varied widely, with 50% inhibitory concentrations (IC50s) ranging from 0.51 +/- 0.13 microM (mean +/- standard deviation) for the most active compound to over 100.0 microM for the least active compounds. The IC50 of the most potent antigiardial agent, 1,3-di(4-amidino-2-methoxyphenoxy)propane compared favorably with the IC50s of the compounds currently used to treat giardiasis, i.e., furazolidone (1.0 +/- 0.03 microM), metronidazole (2.1 +/- 0.80 microM), quinacrine HCl (0.03 +/- 0.02 microM), and tinidazole (0.78 +/- 0.48 microM). A mode of antigiardial activity for these compounds was suggested by the correlation observed between antigiardial activity and the binding of the compounds to calf thymus DNA and poly(dA).poly(dT). PMID- 1929250 TI - In vitro and in vivo evaluation of tiacumicins B and C against Clostridium difficile. AB - Tiacumicins B and C are members of a novel group of 18-membered macrolide antibiotics with in vitro activity against Clostridium difficile. The MICs against 15 strains of C. difficile were 0.12 to 0.25 microgram/ml for tiacumicin B, 0.25 to 1 microgram/ml for tiacumicin C, and 0.5 to 1 microgram/ml for vancomycin. The resistance frequency for both compounds against C. difficile was less than 2.8 x 10(-8) at four and eight times the MIC. The in vivo activities of the tiacumicins against two strains of C. difficile were compared with that of vancomycin in a hamster model of antibiotic-associated colitis. Oral therapy with 0.2, 1, or 5 mg of tiacumicin B or C per kg of body weight protected 100% of clindamycin-treated hamsters exposed to C. difficile ATCC 9689. Oral treatment with identical doses of vancomycin produced a prolonged, dose-dependent survival of hamsters, but it did not prevent the development of fatal colitis at doses of up to 5 mg/kg. When clindamycin-treated animals were exposed to another strain of C. difficile, both tiacumicin B and vancomycin were protective at 5 mg/kg, but not at lower doses. Tiacumicin C was not tested in vivo against the second strain of C. difficile. No tiacumicin B or C was detected in the sera of hamsters treated with single oral doses of 25 mg/kg, while antibiotic levels in the ceca of these hamsters reached 248 micrograms/ml and 285 mg/ml for tiacumicins B and C, respectively. The tiacumicins demonstrated in vitro and in vivo potencies against C. difficile and achieved high concentrations in the cecum, but not the serum, of hamsters after oral administration. PMID- 1929251 TI - Ocular kinetics of pefloxacin after intramuscular administration in albino and pigmented rabbits. AB - We determined the ocular kinetics of pefloxacin, a new fluoroquinolone, when administered by the intramuscular route to albino and pigmented rabbits. In serum of albino rabbits, the area under the concentration-time curve (AUC) for the experimental period was 31.4 +/- 1.07 micrograms.h/ml (mean +/- standard deviation); the AUCs in the aqueous and vitreous humors were high (10.5 +/- 1.90 and 12.4 +/- 3.79 micrograms.h/ml, respectively). Pefloxacin was found in the avascular ocular tissues (30.15 +/- 3.79 micrograms.h/ml in the cornea and 6.98 +/- 1.06 micrograms.h/ml in the lens). In the vascularized tissues, the penetration ratio, defined as tissue AUC/serum AUC, was more than 1. The good intraocular diffusion of pefloxacin might be related to its low molecular weight and to its strong lipophilicity and could explain its clinical efficacy in the treatment of endophthalmitis. In pigmented rabbits, pefloxacin levels were high in the iris (1525 +/- 328 micrograms.h/ml, versus 40.2 +/- 5.08 micrograms.h/ml in albino rabbits) and chorioretina (2600 +/- 422 micrograms.h/ml, versus 48.3 +/ 7.52 micrograms.h/ml in albino rabbits), suggesting that it binds to the pigmentary apparatus. PMID- 1929252 TI - Synthesis and antimicrobial evaluation of dirithromycin (AS-E 136; LY237216), a new macrolide antibiotic derived from erythromycin. AB - Dirithromycin is a 9-N-11-O-oxazine derivative which is formed by condensation of 9(S)-erythromycylamine with 2-(2-methoxyethoxy)acetaldehyde. Dirithromycin is hydrolyzed, either under acidic conditions or in vivo, to its major active metabolite, 9(S)-erythromycylamine. The antimicrobial spectrum of dirithromycin is similar to that of erythromycin; both antibiotics are active against gram positive bacteria, Legionella spp., Helicobacter pylori, and Chlamydia trachomatis. Comparable results were obtained for each antibiotic in MIC and MBC determinations and in the potential development of resistance in vitro. The effects of human serum, bacterial growth media, test methodology, and inoculum size on MICs were similar for each antibiotic. In standard mouse protection studies, dirithromycin was more efficacious than erythromycin against experimental infections after subcutaneous administration of antibiotic. These results were consistent with pharmacokinetic studies in rodents, which showed that dirithromycin gave more persistent concentrations of antibiotic in serum and tissues than were achieved with erythromycin. These studies indicate that dirithromycin possesses antimicrobial activity comparable to that of erythromycin in vitro but is more active than erythromycin in vivo, which may be attributable to the persistence of antimicrobial activity in the tissue(s) of the test animals. PMID- 1929253 TI - Comparative efficacy and safety of cefprozil (BMY-28100) and cefaclor in the treatment of acute group A beta-hemolytic streptococcal pharyngitis. AB - Cefprozil (BMY-28100) is a semisynthetic cephalosporin with broad-spectrum antibacterial activity and prolonged serum elimination half-life allowing for once-a-day oral administration. In vitro, cefprozil demonstrates excellent activity against Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. Cefprozil (500 mg once daily) was compared to cefaclor (250 mg three times daily) in an open, randomized, comparative trial for the treatment of acute group A beta-hemolytic streptococcal pharyngitis. Ninety-four patients were enrolled in this study; 53 patients were evaluable for clinical and bacteriological response assessment. Seventy-eight patients were evaluable for safety assessment. Three patients (all in the cefprozil treatment group) required disenrollment because of side effects, mainly nausea. Clinical and bacteriological responses were comparable for both study drugs. Leukopenia and nausea, the most common side effects observed, were more common in the cefprozil-treated group. Cefprozil appears to be an appropriate alternative to cefaclor for the treatment of acute group A beta-hemolytic streptococcal pharyngitis. However, because of the small number of patients eligible for efficacy assessment, a large type II (beta) error was expected in our study, which may have resulted in a potential failure to detect a difference between both treatment groups. A larger study would be required to determine the proper role of cefprozil in the treatment of group A beta-hemolytic streptococcal infections. PMID- 1929254 TI - Significance of inducible cephalosporinase remaining in the experimentally infected rat granuloma pouch after beta-lactam therapy. AB - We studied the influence of inducible cephalosporinase on levels of secondarily administered beta-lactam antibiotics in exudates using experimentally infected rat granuloma pouches. Cefoperazone or cefmetazole was administered intramuscularly at a dose of 100 mg/kg of body weight to rats at 2 and 8 h after infection of rat pouches with Serratia marcescens W-24, which possesses an inducible type I beta-lactamase (cephalosporinase). Subsequently, cefotaxime or cefbuperazone was administered at an intravenous dose of 100 mg/kg to rats at 24 h postinfection. Levels of cefotaxime in the pouch exudates of the cefmetazole pretreated group were lower than those in the control group, which was infected but not pretreated with antibiotics. This was due to the inactivation of cefotaxime by extracellular cephalosporinase which was induced by cefmetazole and which remained in the rat pouches. However, cefotaxime concentrations were not reduced in the cefoperazone-pretreated group because of the low inducibility of cefoperazone against cephalosporinase production. On the other hand, cefbuperazone concentrations were similar in all groups (control, cefoperazone pretreated, and cefmetazole pretreated), because cefbuperazone is more stable against this enzyme than cefotaxime is. In conclusion, concentrations of secondarily administered beta-lactam antibiotics are affected by inducibly produced cephalosporinase at the infection site when a good inducer like cefmetazole is administered beforehand. PMID- 1929255 TI - Effect of a new quinolone, sparfloxacin, on the pharmacokinetics of theophylline in asthmatic patients. AB - Recently, it has become evident that some quinolones affect the processing of theophylline in the human system. The effect of a new quinolone, sparfloxacin, on the pharmacokinetics and metabolism of theophylline was investigated in six asthmatic patients receiving chronic theophylline therapy (a sustained-release theophylline tablet formulation of 200 to 300 mg twice daily at 12-h intervals). To these patients, sparfloxacin (200 mg once daily) was coadministered for 1 week. Plasma and urine samples were analyzed by high-performance liquid chromatography for theophylline and its metabolites. Plasma theophylline concentration-time curves and the urinary excretion of theophylline and its major metabolites before and after coadministration of sparfloxacin were compared. The total body clearance of theophylline after coadministration of sparfloxacin, 42.81 +/- 6.64 ml/h/kg (mean +/- standard error of the mean), was not significantly different from that after the administration of theophylline alone, 47.11 +/- 7.61 ml/h/kg. Also, no significant change in the urinary excretion of theophylline and its metabolites was observed for subjects receiving or not receiving sparfloxacin. These findings indicate that a once-daily dose of 200 mg of sparfloxacin has no significant effect on the pharmacokinetics and metabolism of theophylline and that it would be safe to coadminister this quinolone to asthmatic patients receiving chronic theophylline therapy. PMID- 1929256 TI - Hippocampal activity in the presence of quinolones and fenbufen in vitro. AB - Rare side effects on the central nervous system including dizziness, restlessness, and even very rare convulsions as reported during the course of antibiotic treatment with quinolones were the topic of a well-controlled in vitro approach. The excitability of brain matter was tested by electrically evoking field potentials in the CA1 region of the rat hippocampus in vitro. Direct effects of nalidixic acid, enoxacin, pefloxacin, norfloxacin, ofloxacin, and ciprofloxacin were found to occur as a dose-dependent increase in amplitude of this field potential, which is in line with the view that the quinolones increase excitability. The highest increase was found with enoxacin and nalidixic acid, and the lowest increase was found with ciprofloxacin. In order to keep the potential risk of the antibiotic therapy as low as possible, ciprofloxacin might be the drug of choice of the quinolones. In contrast to the quinolones, which only increased the amplitudes of electrically evoked potentials, fenbufen induced spontaneous firing in the pyramidal cell layer without stimulation in addition to its dose-dependent effects on the amplitudes of the evoked potentials. Threshold doses of the quinolones tested (0.25 microM) increased the amplitudes of evoked potentials in the presence of an otherwise ineffective concentration of fenbufen (1 microM) to different degrees, ranging from 39.2% for ciprofloxacin to 72.6% for enoxacin. PMID- 1929257 TI - Beta-lactam antibiotics potentiate magainin 2 antimicrobial activity in vitro and in vivo. AB - The ability of magainin 2 to augment antibiotic therapy was examined. Susceptibility to magainin 2 was determined on Escherichia coli incubated in the presence and absence of sublethal concentrations of antibiotics both in vitro and in vivo. Experiments in buffer and normal human serum revealed that E. coli exposed to sublethal amounts of cefepime, a beta-lactam antibiotic, was significantly more susceptible to the antimicrobial activity of magainin 2. Bacteria incubated with subinhibitory concentrations of other beta-lactam type antibiotics, but not amikacin (an aminoglycoside) or ciprofloxacin (a quinolone), were also more susceptible to magainin 2 in normal human serum. Bacteria were less susceptible to magainin 2 when they were examined in heat-inactivated serum. Complement was shown to be required for magainin 2 activity in serum by using C8 deficient sera. The combination of magainin 2 and cefepime was shown to be more antimicrobial in normal human serum for a variety of bacterial strains. Magainin 2 was completely inactive as a therapeutic agent when it was administered alone (2 mg per mouse) but significantly increased the survival of mice when it was administered with a low level of cefepime. PMID- 1929258 TI - Drug level monitoring in a double-blind multicenter trial: false-positive zidovudine measurements in AIDS clinical trials group protocol 019. AB - Twenty-three different laboratories using four different assay methods reported zidovudine (ZDV; azidothymidine) measurements in a double-blind trial of ZDV for asymptomatic human immunodeficiency virus-infected patients (AIDS Clinical Trials Group Protocol 019). The risk of false-positive ZDV measurements was defined with coded specimens containing no ZDV in a quality control testing program. This testing identified six problem laboratories which reported ZDV levels of greater than or equal to 100 ng/ml for specimens with no ZDV; all of these laboratories used high-performance liquid chromatography. These six laboratories reported a disproportionately high fraction of positive assays for subjects randomized to the placebo group (31% for these 6 laboratories versus 4% for the other 17 laboratories; P less than 0.0001). The high number of false-positive ZDV results reported by these six laboratories suggested that many of the positive results that they reported for patient specimens were also false-positive results. This hypothesis was examined by retesting specimens from patients in the placebo group that had been reported as positive by these laboratories. Ninety percent (19 of 21) of these specimens were negative on retesting at the reference laboratory. These results confirm the hypothesis; they demonstrate the need for quality control testing to avoid the misinterpretation of multicenter trials because of incorrect laboratory data. PMID- 1929259 TI - Metabolic disposition and pharmacokinetics of the antiviral agent 6-methoxypurine arabinoside in rats and monkeys. AB - The metabolism and pharmacokinetics of 6-methoxypurine arabinoside (ara-M), a potent and selective inhibitor of varicella-zoster virus, were investigated in rats and monkeys. In Long Evans rats, orally administered [8-14C]ara-M (10 mg/kg) was well absorbed but extensively metabolized to hypoxanthine arabinoside (ara H), hypoxanthine, xanthine, uric acid, and allantoin. Only 4% of an oral dose was recovered in the urine as unchanged drug, compared with 40% of an intravenous dose, indicating significant presystemic metabolism. Pretreatment of rats with 1 aminobenzotriazole, an inhibitor of cytochrome P-450, did not alter this metabolism. Pretreatment with deoxycoformycin or erythro-9-(2-hydroxy-3 nonyl)adenine hydrochloride, inhibitors of adenosine deaminase, resulted in a marked decrease in ara-M metabolism, indicating that adenosine deaminase plays a major role in the biotransformation of ara-M. In cynomolgus monkeys, [8-14C]ara-M (10 mg/kg) administered intravenously or orally was extensively metabolized to ara-H. Several minor urinary metabolites were detected in both rats and monkeys. However, adenine arabinoside was not found in urine or plasma from either rats or monkeys after administration of ara-M, except for a very low level detected in the urine of rats pretreated with deoxycoformycin. The elimination half-lives of intravenously administered ara-M in rats and monkeys were 29 and 45 min, respectively. The corresponding half-lives of the primary metabolite, ara-H, were 44 min and 2.3 h. Plasma profiles of orally administered ara-M in both rats and monkeys demonstrated the poor oral bioavailability of this arabinoside. The results of these studies indicate that ara-M is not well suited for oral administration because of extensive presystemic metabolism. PMID- 1929261 TI - Kinetics and dynamics of tobramycin action in patients with bacteriuria given single doses. AB - We studied the effect of a single intravenous dose of tobramycin on the rate of bacterial eradication from urine in 10 patients with bladder catheters. The catheter was replaced 4 to 6 h after the tobramycin dose. Pseudomonas aeruginosa was found in 7 of the 10 patients, while members of the family Enterobacteriaceae accounted for the remaining pathogens. The MIC for each bacterium was determined in both broth and urine. Tobramycin eradicated the bacteria from eight patients. Bacteriuria resolved in 21.8 +/- 18.0 h, and urine bactericidal activity persisted for 43.4 +/- 20.3 h after the dose of tobramycin. Most patients were recolonized by another bacterial species if use of Foley catheters was resumed on a continuous basis. Two patients required additional doses of tobramycin to eradicate the original pathogen. There were significant temporal relationships between the pharmacokinetics of tobramycin and the change in colony count of bacteria in urine. PMID- 1929260 TI - In vitro susceptibilities of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum to sparfloxacin and PD 127391. AB - The in vitro activities of two investigational quinolones, sparfloxacin (previously designated AT 4140) and PD 127391, were determined for 30 strains each of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum and compared with those of ciprofloxacin, tetracycline, clindamycin, and erythromycin. Erythromycin was the most active compound against M. pneumoniae (maximum MIC, less than 0.008 microgram/ml). PD 127391 (MICs, less than 0.008 to 0.031 microgram/ml), sparfloxacin (MICs, less than 0.008 to 0.25 microgram/ml), clindamycin (MICs, less than 0.008 to 0.5 microgram/ml), and tetracycline (MICs, 0.063 to 0.25 microgram/ml) were superior to ciprofloxacin (MICs, 0.5 to 2 microgram/ml). Sparfloxacin and PD 127391 were active against M. hominis (MICs, less than 0.008 to 0.031 microgram/ml for each) at concentrations comparable to those of clindamycin (MICs, less than 0.008 to 0.063 microgram/ml) and at concentrations lower than those of ciprofloxacin (MICs, 0.125 to 0.5 microgram/ml). As expected, M. hominis was resistant to erythromycin (MICs, 32 to greater than or equal to 256 micrograms/ml). For U. urealyticum, PD 127391 (MICs, 0.031 to 0.5 microgram/ml) and sparfloxacin (MICs, 0.063 to 1 microgram/ml) were superior to erythromycin (MICs, 0.25 to 4 micrograms/ml), ciprofloxacin (MICs, 0.5 to 8 micrograms/ml), and clindamycin (MICs, 0.25 to 64 micrograms/ml. Both new quinolones were equally active against tetracycline-susceptible as well as resistant strains of M. hominis and U. urealyticum. The possible influence of medium components and/or pH on MICs was evaluated by testing a Staphylococcus aureus reference strain with each antibiotic in SP-4 broth and 10-B broth and comparing the results with published MICs for this strain. MICs determined in 10 B broth for erythromycin were affected most. This study shows that the activities of sparfloxacin and PD 127391 are similar to one another and comparable or superior to those of other drugs used to treat mycoplasmal infections. The MICs of both new quinolones were consistently 2 to several dilutions lower than those of ciprofloxacin for each species. PMID- 1929262 TI - Comparison of spiral gradient and conventional agar dilution for susceptibility testing of anaerobic bacteria. AB - Antimicrobial susceptibility tests were performed on brucella laked blood agar with 340 isolates and 14 antimicrobial agents by the standard agar dilution technique and the spiral gradient technique in which antibiotic concentrations were established by diffusion from the agar surface. For comparison, spiral gradient MICs were determined by calculating antimicrobial concentrations at growth endpoints and rounding up to the next twofold incremental concentration. The cumulative percentage of strains susceptible at the breakpoint determined from spiral gradient data was within 10%, generally, of the percentage of strains susceptible at the breakpoint determined from agar dilution data. The overall agreement between the two techniques (within one doubling dilution) was 90.6%. The spiral gradient agar dilution technique is a reasonable alternative to the conventional agar dilution technique for susceptibility testing of anaerobic bacteria. PMID- 1929263 TI - Comparative pharmacokinetics of amphotericin B after administration of a novel colloidal delivery system, ABCD, and a conventional formulation to rats. AB - The pharmacokinetics and tissue distribution of two amphotericin B dosage forms were compared in rats. A novel lipid-based colloidal delivery system for amphotericin B (Amphotericin B Colloidal Dispersion [ABCD]) which reduces the toxicity of amphotericin B in animals was compared with a conventional micellar formulation. Male Sprague-Dawley rats received a single intravenous injection of 1.0 mg of ABCD, 5.0 mg of ABCD, or 1.0 mg of micellar amphotericin B per kg. Plasma and tissue samples were obtained at 0.5 to 96 h after dosing and analyzed for amphotericin B by high-pressure liquid chromatography. Animals receiving ABCD demonstrated reduced peak levels in plasma, a three- to sevenfold reduction in amphotericin B delivery to the kidneys (the major target organ for toxicity), and prolonged residence time compared with those receiving the micellar formulation. In contrast, amphotericin B concentrations in the liver were two- to threefold higher with ABCD than with the micellar formulation: nearly 100% of the amphotericin B administered as ABCD was recovered from the liver 30 min after dosing. These results suggest that the colloidal particles of ABCD are taken up by the liver, which then acts as a reservoir of amphotericin B. PMID- 1929264 TI - Susceptibilities of 394 Bacteroides fragilis, non-B. fragilis group Bacteroides species, and Fusobacterium species to newer antimicrobial agents. AB - The susceptibilities of 374 selected beta-lactamase-producing gram-negative anaerobes (including 22 cefoxitin-resistant strains and 36 strains refractory to the enhancing effect of beta-lactamase inhibitors) and 20 beta-lactamase-negative strains were tested by agar dilution against selected new agents. The organisms included 217 Bacteroides fragilis group strains, 137 non-B. fragilis group Bacteroides spp., and 40 fusobacteria. All strains were susceptible to piperacillin-tazobactam, imipenem, and meropenem. For the B. fragilis group, 96% were susceptible to ampicillin-sulbactam, 95% were susceptible to amoxicillin clavulanate and cefoperazone-sulbactam, 94% were susceptible to tosufloxacin, 91% were susceptible to cefoxitin, 88% were susceptible to trospectomycin, and 73% were susceptible to cefotetan. For the beta-lactamase-positive non-B. fragilis group Bacteroides spp., greater than or equal to 94% were susceptible to cefoxitin, amoxicillin-clavulanate, ampicillin-sulbactam, cefoperazone-sulbactam, and trospectomycin, 90% were susceptible to cefotetan, and 85% were susceptible to tosufloxacin (the most resistant strains were B. bivius and B. disiens). For the beta-lactamase-positive fusobacteria, greater than or equal to 97% were susceptible to amoxicillin-clavulanate, ampicillin-sulbactam, cefoperazone sulbactam, trospectomycin, and cefoxitin, 90% were susceptible to cefotetan, and 89% were susceptible to tosufloxacin. All agents showed excellent activity against beta-lactamase-negative strains (for trospectomycin, 95% were susceptible; for all other drugs, 100% were susceptible). Overall, both carbapenems and piperacillin-tazobactam were most active. Amoxicillin clavulanate, ampicillin-sulbactam, and cefoperazone-sulbactam lacked activity against some cefoxitin-resistant B. fragilis group strains but had excellent activity against other organisms. Tosufloxacin, a new quinolone, had very good activity against B. fragilis group strains (94% susceptible), good activity against other beta-lactamase-positive strains (less than or equal 85% susceptible), and excellent activity against beta-lactamase-negative strains (100% susceptible; MIC for 90% of strains, 0.5 microgram/ml). Trospectomycin was active against >90% of all strains except for B. fragilis group strains (88% susceptible; MIC for 90% of strains, 32 microgram/ml). Clinical studies are required to delineate the role of newer agents in the therapy of anaerobic infections. PMID- 1929265 TI - Effect of beta-lactamase inhibitors on the activities of various beta-lactam agents against anaerobic bacteria. AB - The in vitro activities of several new beta-lactam-beta-lactamase inhibitor combinations (piperacillin plus tazobactam, ceftizoxime and cefonicid with sulbactam and clavulanic acid, and ampicillin plus 8 micrograms of sulbactam per ml) were tested with anaerobic bacteria and compared with known beta-lactam-beta lactamase inhibitor combinations and other potent antianaerobe agents. All the combinations tested (except for the cefonicid-inhibitor combinations) were active against almost all strains of the Bacteroides fragilis group. This report indicates that beta-lactamase inhibitors may improve the activity of beta-lactam agents with marginal activity against the B. fragilis group. PMID- 1929266 TI - Susceptibility of Pneumocystis carinii to artemisinin in vitro. AB - The susceptibility of Pneumocystis carinii to artemisinin (qinghaosu) was determined in short-term primary culture. In untreated cultures, trophozoites increased an average of fivefold over 4 days. Inhibition of parasite growth in cultures treated with artemisinin at concentrations as low as 0.5 microM was seen. In contrast, artemisinin concentrations up to 100 microM had no effect on feeder layer cells. PMID- 1929267 TI - Cocaine hydrochloride and benzoylecgonine have no in vitro inhibitory effect against Neisseria gonorrhoeae. AB - We evaluated 72 clinical Neisseria gonorrhoeae isolates for in vitro susceptibility to cocaine hydrochloride and its metabolite benzoylecgonine and to penicillin, tetracycline, erythromycin, ceftriaxone, and ofloxacin. Although there was a wide range of susceptibilities to the antimicrobial agents, cocaine and its major metabolite, benzoylecgonine, had no demonstrable antigonococcal activity. Cocaine use is frequently associated with outbreaks of sexually transmitted disease. We hypothesized that the dramatically decreasing incidence of gonorrhea over the past 15 years may be in part due to pharmacological effects of cocaine. However, since cocaine and its metabolite have no in vitro antigonococcal activity, this hypothesis is unlikely. PMID- 1929268 TI - In vitro activity of metronidazole against Helicobacter pylori as determined by agar dilution and agar diffusion. AB - Metronidazole activity against 25 clinical isolates of Helicobacter pylori was evaluated by agar dilution, epsilometer (E-test; AB Biodisk, Solna, Sweden), and disk diffusion methods after 3 and 5 days of incubation in a microaerophilic atmosphere. Agar dilution, performed in duplicate, provided reproducible results with MICs for 50% of the isolates of less than or equal to 0.12 microgram/ml after 3 and 5 days of incubation and MICs for 90% of the isolates of 2 and 4 micrograms/ml after 3 and 5 days of incubation, respectively. Reproducibility of MICs was slightly better after 5 days than after 3 days of incubation. MICs obtained with the E-test were higher, with 76 and 68% of isolates inhibited by less than or equal to 16 micrograms of metronidazole per ml after 3 and 5 days, respectively, in contrast with corresponding values of 92 and 88% for agar dilution. Zone diameters obtained with the commercially available 80-micrograms metronidazole elution disk were too large (greater than or equal to 41 mm) to allow discrimination between susceptible and resistant isolates, although resistant subpopulations were detected by the appearance of inner colonies in four isolates. In conclusion, the E-test was easy to perform and interpret, and it appeared to be more likely than agar dilution to detect metronidazole resistance in vitro in H. pylori. PMID- 1929269 TI - In vitro activities of aminoglycosides, lincosamides, and rifamycins against Mycobacterium leprae. AB - The in vitro activities of a variety of aminoglycosides, lincosamides, and rifamycins against Mycobacterium leprae were evaluated with the BACTEC 460 system. At 20 micrograms/ml, gentamicin, kanamycin, tobramycin, streptomycin, and amikacin were inactive. Lincomycin was active at 20 micrograms/ml, and clindamycin was active at 0.31 micrograms/ml. Rifamycin SV, rifabutin, and rifampin were active at 3.1, 3.1 to 12.5, and 200 ng/ml, respectively. The in vitro assay correlates well with the in vivo response of M. leprae to antimicrobial agents, with the exception of the aminoglycosides. PMID- 1929270 TI - In vitro susceptibility testing procedures for fosfomycin tromethamine. AB - Fosfomycin tromethamine (previously fosfomycin trometamol) is an orally administered fosfomycin which may be used for single-dose therapy of uncomplicated urinary tract infections. Fosfomycin tromethamine, norfloxacin, and trimethoprim-sulfamethoxazole inhibited greater than 90% of 352 bacterial isolates representing 25 different species; trimethoprim and nalidixic acid had narrower spectrums of activity. Strains of Escherichia, Citrobacter, Enterobacter, and Klebsiella species were much more susceptible when glucose-6 phosphate was added to the test medium, but isolates belonging to other genera were not affected. PMID- 1929271 TI - Accidental overdose of intravenous ofloxacin with benign outcome. AB - A patient accidentally received approximately 3 g of ofloxacin intravenously. She experienced only moderately severe central nervous system symptoms, which resolved within 9 h. The peak serum ofloxacin level was 39.3 micrograms/ml, approximately seven times the usual peak level. Ofloxacin may possess a considerable safety margin in humans. PMID- 1929272 TI - Long-term prophylaxis with norfloxacin versus nitrofurantoin in women with recurrent urinary tract infection. AB - A total of 102 women with recurrent urinary tract infections were included in this open randomized study; 55 received 200 mg of norfloxacin daily and 47 received 50 mg of nitrofurantoin daily over 6 months. Fifty-three and 41 women from the norfloxacin- and nitrofurantoin-treated groups, respectively, completed the 6-month follow-up period. Forty-four (81%) of the norfloxacin-treated patients and 27 (65%) of the nitrofurantoin-treated patients remained free of symptoms (P = 0.05), and urine samples from 49 (92.4%) and 29 (70.7%) of the patients, respectively, were sterile (P less than 0.005). Side effects occurred with similar frequencies in both groups (15 and 17%) but were more severe in the women who received nitrofurantoin. Despite the better results obtained with norfloxacin, the difference in the costs of the two agents must be considered. PMID- 1929273 TI - Efficacy of different beta-lactams against an extended-spectrum beta-lactamase producing Klebsiella pneumoniae strain in the rat intra-abdominal abscess model. AB - Although standard-inoculum MICs were within the susceptible range for all compounds, cefoperazone, cefotaxime, and cefpirome were significantly less effective than imipenem or the combination of cefoperazone and sulbactam in the treatment of rat intra-abdominal abscesses due to an extended-spectrum beta lactamase-producing strain of Klebsiella pneumoniae. PMID- 1929274 TI - In vitro and in vivo studies of ME1228, a new parenteral cephalosporin with potent activity against Pseudomonas aeruginosa. AB - The therapeutic effect of ME1228, a new parenteral cephalosporin, was compared with that of broad-spectrum cephems in normal and neutropenic mice infected with various species of bacteria. The results showed that ME1228 was more active than were the other cephems against infections with various pathogens. PMID- 1929275 TI - Pharmacokinetics of 2',3'-dideoxyinosine in monkeys. AB - Comparison of the pharmacokinetic parameters obtained for dideoxyinosine (ddI) in monkeys with those obtained for humans indicates that the monkey is an appropriate animal model for ddI pharmacokinetics in humans. Following intravenous administration of 20 mg of ddI per kg of body weight and measurement of ddI in plasma and urine by high-performance liquid chromatography, pharmacokinetic parameters were determined by noncompartmental analysis. Total systemic clearance was 0.74 liters/h/kg, volume of distribution was 0.92 liters/kg, and the elimination half-life of ddI was 1.22 h. The pharmacokinetics of ddI in five monkeys were determined following intravenous administration of 20 mg/kg and were found to be comparable to those obtained in patients with AIDS. PMID- 1929277 TI - Use of slime dispersants to promote antibiotic penetration through the extracellular polysaccharide of mucoid Pseudomonas aeruginosa. AB - Agents with the potential to reduce Pseudomonas aeruginosa alginate viscosity (slime dispersants) were shown to promote the diffusion of antipseudomonal antibiotics through alginate but were more effective in facilitating the diffusion of gentamicin than that of ceftazidime. EDTA increased the diffusion rates of these antibiotics by factors of 4.0 and 1.5, respectively, although sodium chloride significantly reduced viscosity and enhanced gentamicin diffusion. PMID- 1929276 TI - Comparative inhibition of hepatitis B virus DNA polymerase and cellular DNA polymerases by triphosphates of sugar-modified 5-methyldeoxycytidines and of other nucleoside analogs. AB - Of a series of 14 nucleoside 5'-triphosphates, those of 2',3'-dideoxy-3'-fluoro-5 methylcytidine, 3'-azido-2',3'-dideoxy-5-methylcytidine, 2',3'-dideoxy-3' fluoroguanosine, 2',3'-didehydro-2',3'-dideoxy-5-methylcytidine, 2',3'-dideoxy-3' fluoro-5-ethylcytidine, and 2',3'-dideoxy-3'-fluoroadenosine emerged as the most potent inhibitors of hepatitis B virus DNA polymerase (50% inhibitory dose, 0.03 to 0.35 microM). In contrast, cellular DNA polymerases proved to be resistant to (alpha) or partially affected by (beta) these analogs. These compounds are among the most effective and selective inhibitors of endogenous hepatitis B virus DNA polymerase recognized to date. PMID- 1929278 TI - Human serum enhances the postantibiotic effect of fluoroquinolones against Staphylococcus aureus. AB - The postantibiotic effect (PAE) of fluoroquinolones against Staphylococcus aureus was determined in Mueller-Hinton broth and normal human serum. At both 4X and 10X the MIC, serum significantly increased the duration of the PAE in all strains tested (P less than 0.05). Reducing the pH of the serum from 7.9 to 7.2 had no effect on the PAE. Heat treating the serum (56 degrees C, 30 min) reduced the PAE of ciprofloxacin at 10X the MIC approximately 25% (P less than 0.05). The PAE of cloxacillin was reduced approximately 80% in serum, and PAE experiments with gentamicin and cephalexin produced findings similar to those obtained with the fluoroquinolones. Serum increased the MICs of ciprofloxacin and norfloxacin less than twofold and increased the MIC of pefloxacin approximately fourfold. We conclude that normal human serum considerably increases the PAE of fluoroquinolones against S. aureus. PMID- 1929279 TI - Use of high-performance liquid chromatography to monitor stability of tetracycline and chlortetracycline in susceptibility determinations. AB - Trypticase soy broth and nutrient broth were used in the antimicrobial susceptibility testing of tetracycline and chlortetracycline with Bacillus subtilis. The stability of the antibiotics in both media at an incubation temperature of 37 degrees C was monitored by high-performance liquid chromatography. It was found that Trypticase soy broth has limited application in susceptibility testing for the tetracycline congeners tested and that chlortetracycline is more unstable than tetracycline. PMID- 1929280 TI - Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. PMID- 1929281 TI - Intrinsic and unusual resistance to macrolide, lincosamide, and streptogramin antibiotics in bacteria. PMID- 1929282 TI - Molecular cloning, purification, and properties of a plasmid-encoded chloramphenicol acetyltransferase from Staphylococcus haemolyticus. AB - A small chloramphenicol resistance (Cmr) plasmid of approximately 3.75 kb, designated pSCS5, was isolated from Staphylococcus haemolyticus. This plasmid encoded an inducible chloramphenicol acetyltransferase (CAT; EC 2.3.1.28). The cat gene of pSCS5 was cloned into the Escherichia coli plasmid vector pBluescript SKII+. It differed in its nucleotide sequence and deduced amino acid sequence from the cat genes described previously in staphylococci and other gram-positive bacteria. The CAT enzyme was purified from cell-free lysates by ammonium sulfate precipitation, ion-exchange chromatography, and fast protein liquid chromatography. The native enzyme had an Mr of 70,000 and was composed of three identical subunits, each with an Mr of approximately 23,000. Its isoelectric point was at pH 6.15. CAT from pSCS5 exhibited Km values of 2.81 and 51.8 microM for chloramphenicol and acetyl coenzyme A, respectively. The optimum pH for activity was 7.8. CAT encoded by pSCS5 proved to be relatively heat stable, but sensitive to mercury ions. The observed differences in the nucleotide sequence and the biochemical characteristics of the enzyme allowed the identification of the pSCS5-encoded CAT from S. haemolyticus as a CAT variant different from those described previously in gram-positive bacteria. PMID- 1929283 TI - Aminoglycoside resistance and aminoglycoside usage: ten years of experience in one hospital. AB - For 10 years the 700-bed Minneapolis Veterans Affairs Medical Center has conducted a policy of carefully controlled aminoglycoside usage and monitoring of resistance of over 25,000 aerobic and facultative gram-negative bacillary isolates to the aminoglycosides. On two occasions during the 1980s, our experience of introducing amikacin at a high level of usage was associated with a significant reduction in resistance to gentamicin and tobramycin among gram negative bacilli. Rapid reintroduction of gentamicin usage in 1982 after the first amikacin period was associated with a significant and rapid increase in gentamicin and tobramycin resistance. However, in 1986, gentamicin was again reintroduced to this institution at an initially modest level, and the percentage of usage of gentamicin was gradually increased over a 15-month period without a significant change in resistance to gentamicin, tobramycin, or amikacin while maintaining an overall 68% gentamicin usage and 30% amikacin usage. Aminoglycoside usage (measured as patient days) rose steadily from under 2,000 patient days per quarter in 1980 and 1981 to over 3,000 days per quarter in 1985. Since 1985, usage has declined to under 2,500 patient days per quarter in 1990. This usage rise and fall occurred during a steadily declining daily patient census that was 590 in 1980 and 465 in 1989. A move to a new hospital building in June 1988 was associated with an additional significant decline in resistance to all aminoglycosides (P less than 0.05), continuing a trend that was evident for the year preceding the move. Resistance to aminoglycoside antibiotics is now at the lowest level in 10 years at this institution, with only one gram-negative organism, Pseudomonas aeruginosa, that exhibits more than 5% resistance to gentamicin and no gram-negative species that are more than 5% resistant to amikacin and tobramycin. PMID- 1929284 TI - Mechanisms of interaction among subinhibitory concentrations of antibiotics, human polymorphonuclear neutrophils, and gram-negative bacilli. AB - Our hypothesis was that pretreatment of bacteria with subinhibitory concentrations (sub-MICs) of antibiotics enhances the susceptibility of the organisms to killing by human polymorphonuclear neutrophils (PMNs). Our purpose was to study a variety of drugs with different mechanisms of action and to determine whether the mechanism and locus of action altered the sub-MIC effect. The following outcome measures were used: ingestion and killing of bacteria by PMNs, bacterial killing in the absence of phagosome formation, and binding requirements of the bacteria to PMNs. The antibiotics used were representative of a variety of classes, including beta-lactams (piperacillin and imipenem) and quinolones (ciprofloxacin). Bacterial uptake and killing were measured by using standard techniques, and results were analyzed by using the analysis-of-variance technique and Dunnett's t test. Pretreatment of Escherichia coli with all drugs showed significantly enhanced killing of bacteria by PMNs, which was independent of ingestion by the phagocytes. Even in the absence of phagosome formation, statistically significant killing persisted with piperacillin-pretreated bacteria but not with imipenem- or ciprofloxacin-pretreated organisms. The opsonization experiments showed that contact between bacteria and PMNs was necessary for killing to occur. The sub-MIC effect appears to be independent of the locus or mechanism of action of the antibiotic. It results in enhanced killing by PMNs which is independent of ingestion and also may persist even in the absence of phagosome formation. Killing is dependent upon specific contact between bacteria and an intact phagocyte. PMID- 1929285 TI - Effects of intravitreal dexamethasone on concentration of intravitreal vancomycin in experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis. AB - Intravitreal corticosteroids in the treatment of bacterial endophthalmitis remain controversial. We utilized an experimental rabbit model of methicillin-resistant Staphylococcus epidermidis endophthalmitis (i) to calculate the intravitreal vancomycin concentration in rabbit eyes receiving intravitreal vancomycin alone or in combination with intravitreal dexamethasone and (ii) to determine whether an intravitreal steroid has any effect on intravitreal vancomycin levels. All right eyes were infected and all left eyes were uninfected. The rabbits were divided into two treatment groups: (i) 32 eyes (group I) were injected with intravitreal vancomycin, 1.0 mg (0.1 ml); (ii) 32 additional eyes (group II) were injected with intravitreal dexamethasone, 400 micrograms (0.1 ml), in addition to vancomycin. Measurement of intravitreal vancomycin concentration was performed following sacrifice, utilizing a microbiologic agar diffusion assay. Analyses of intravitreal vancomycin concentrations were performed by using model-independent parameters, with area under the concentration-time curves derived by trapezoidal approximation. The intravitreal vancomycin concentration was significantly lower in both uninfected and infected group II eyes (P less than 0.002). Analysis of intravitreal vancomycin concentration-time relationships was performed by using a nonlinear least-squares regression program; data best fit a one-compartment model. In addition, no vancomycin-dexamethasone interaction could be demonstrated. The reduced level of intravitreal vancomycin in the presence of intravitreal dexamethasone may have important clinical implications. PMID- 1929286 TI - Limited protection by small unilamellar liposomes against the renal tubular toxicity induced by repeated amphotericin B infusions in rats. AB - Amphotericin B (AMB), either alone or incorporated into small unilamellar vesicles of pure dipalmitoylphosphatidyl choline (DPPC SUV-AMB), was administered intravenously to male Sprague-Dawley rats once daily for 5 days. Either 1.5 or 3.5 mg of AMB or DPPC SUV-AMB per kg was given, since these concentrations corresponded, respectively, to the lowest nephrotoxic dose and the sublethal dose of AMB in our model. Tubular functions were evaluated daily, and AMB concentrations in plasma, urine, and tissues were measured by high-performance liquid chromatography. AMB at both doses induced tubular toxicity, hyposthenuria being the earliest symptom. DPPC SUV-AMB at 1.5 mg/kg/day was atoxic, but the tubular alterations induced by 3.5 mg of DPPC SUV-AMB per kg were similar to those observed with 3.5 mg of AMB per kg, except that the ability to concentrate urine was partly restored 72 h after the last infusion. Incorporating AMB into DPPC SUV did not influence the pharmacokinetics of the drug. Using this lipidic AMB formulation, we thus observed a beneficial effect toward limiting the renal tubular toxicity of repeated low doses of AMB but, unexpectedly, not that of high doses. These results indicate that tubular renal functions and electrolyte serum values should be closely monitored in patients treated with AMB liposomal formulations, especially high-dose regimens. PMID- 1929287 TI - 5'-Alkyl-substituted analogs of 5'-methylthioadenosine as trypanocides. AB - 5'-Deoxy-5'-(methylthio)adenosine (MTA) is a by-product of polyamine metabolism and is phosphoryolytically cleaved to adenine and 5-deoxy-5-(methylthio)ribose-1 phosphate (MTR-1-P) by MTA phosphorylase. In eukaryotes, adenine is subsequently salvaged and converted to nucleotides, while MTR-1-P is converted to methionine. We examined 5'-deoxy-5'-substituted analogs of MTA for trypanocidal activity in vitro and in vivo. 5'-Deoxy-5'-(hydroxyethyl)thioadenosine (HETA) and its 5' bromo,5'-chloro and 5'-fluoro derivatives were cleaved by extracts of the African trypanosome Trypanosoma brucei brucei (Km for MTA, 11.5 microM; Km for HETA, 13.2 microM) in a phosphate-dependent reaction. HETA and the three halo analogs were 50% inhibitory to growth at 0.5 to 5.0 microM in vitro. Inhibition of growth was reversible by exogenous methionine and 2-keto-4-methylthiobutyric acid, an intermediate in methionine synthesis from MTR-1-P. HETA was selected for further study in vivo. When administered by miniosmotic pump (25 to 150 mg/kg/day for 7 days) to mice infected with T. brucei brucei, HETA effected 70 to 90% cure rates. Results of this study indicate that these analogs of MTA are converted to trypanocidal MTR-1-P analogs and that this approach deserves further consideration in the development of novel chemotherapy of trypanosomiasis. PMID- 1929289 TI - Efficacy of cilofungin alone and in combination with amphotericin B in a murine model of disseminated aspergillosis. AB - Cilofungin, amphotericin B, and a combination of the two drugs were compared in a model of aspergillosis in immunocompetent mice in three experiments. Cilofungin was equivalent to amphotericin B in preventing death and eradicating cerebral aspergillosis, but it did not sterilize the kidneys. This is the first demonstration of the in vivo activity of cilofungin against any fungus other than Candida albicans. The mortality with combination therapy was higher than those with amphotericin B alone (P = 0.003) and cilofungin alone (P = 0.054), as was weight loss after infection, indicating antagonism between cilofungin and amphotericin B in this model. The mechanisms of action and antagonism remain to be explained. PMID- 1929288 TI - Antifungal effects of the nonlinear pharmacokinetics of cilofungin, a 1,3-beta glucan synthetase inhibitor, during continuous and intermittent intravenous infusions in treatment of experimental disseminated candidiasis. AB - Cilofungin (LY-121019) is a fungicidal cell wall-active 1,3-beta-glucan synthetase inhibitor with a short plasma half-life and saturable nonlinear plasma pharmacokinetics. To optimize the in vivo efficacy of this compound, we studied the effects of its linear and nonlinear pharmacokinetics during continuous versus intermittent intravenous infusion of cilofungin in the treatment of experimental disseminated candidiasis in persistently granulocytopenic rabbits. Six groups of rabbits were studied, untreated controls (n = 32) and five cilofungin dosage regimen groups consisting of the following: 25 mg/kg of body weight intravenously twice daily (VLoINT) (n = 9); 50 mg/kg twice daily (LoINT) (n = 9); 90 mg/kg twice daily (HiINT) (n = 11); 5 mg/kg/h for 18 h/day (LoCI) (n = 7); and 10 mg/kg/h for 18 h/day (HiCI) (n = 7). All regimens achieved plasma concentrations exceeding the MIC for Candida albicans (0.25 microgram/ml). In vitro timed kill assays found that the fungicidal activity and rate of kill by cilofungin above the MIC for C. albicans was concentration dependent. At the lower dosage regimens (VLoINT, LoINT, and LoCI), cilofungin followed linear plasma pharmacokinetics, whereas at higher doses (HiCI and HiINT), nonlinear kinetics consistent with a saturated elimination pathway(s) were observed. Only HiCI and HiINT produced a 10(3)- to 10(4)-fold reduction in CFU per gram in candidiasis of the brain (P less than or equal to 0.001). HiCI and HiINT also significantly reduced infection in the choroid (P less than or equal to 0.05). All regimens, except VLoInt, significantly (P less than or equal to 0.01) reduced tissue infections in lung, liver, spleen, and kidney. However, only the regimens with nonlinear saturation kinetics (HiCI and HiINT) produced a 10(6) reduction in the spleen and a > 10(5) reduction of C. albicans in the kidney and liver. A simple doubling of the dosage from LoCI to HiCI resulted in tissue concentrations that were 10 times higher and a 10(2)- to 10(4)-fold-greater antifungal effect. There was a direct correlation (r2 = 0.83) between tissue concentrations of cilofungin and antifungal activity. Thus, continuous and intermittent infusion dosage regimens that elicit nonlinear saturation plasma pharmacokinetics of cilofungin were associated with increased antifungal activity against experimental disseminated candidiasis. PMID- 1929290 TI - Synergy between cilofungin and amphotericin B in a murine model of candidiasis. AB - The efficacies of cilofungin and amphotericin B separately and together in mice with disseminated candidiasis were studied. Male CD-1 mice (age, 5 weeks) were infected intravenously with 3 X 10(5) CFU of Candida albicans. At 4 days postinfection, intraperitoneal therapy was initiated and was continued for 14 days. Therapy groups included those given cilofungin at 6.25 or 62.5 mg/kg/day (given twice daily), amphotericin B at 0.625 mg/kg/day (given once daily), cilofungin at 6.25 mg/kg/day plus amphotericin B, and cilofungin at 62.5 mg/kg/day plus amphotericin B. Mice were observed through 30 days postinfection. All infected untreated mice died of infection between days 6 and 18. Eighty-five percent of mice receiving cilofungin at 6.25 mg/kg/day died between days 13 and 30. All other mice survived. Quantitative determination of the number of CFU of C. albicans in the spleens and kidneys of all survivors revealed that mice that had received both drugs had lower residual burdens of C. albicans. All mice treated with cilofungin at 62.5 mg/kg/day plus amphotericin B had sterile spleens, whereas 42 to 58% of mice given cilofungin or amphotericin B monotherapy had sterile spleens. All kidneys were infected in mice which had received cilofungin at 62.5 mg/kg/day or amphotericin B. Neither organ was infected in 17% of each group receiving combination therapy with cilofungin and amphotericin B. The number of CFU in the kidneys of mice treated with cilofungin at 62.5 mg/kg/day plus amphotericin B was lower than those cultured from mice treated with cilofungin at 62.5 mg/kg/day (P less than 0.001, Mann-Whitney) or amhotericin B (P less than 0.05). Modest synergy was noted in inhibition of the C. albicans isolate in vitro. Pharmacokinetic studies showed elevated levels of cilofungin but not amphotericin B in sera of mice treated with combined therapy compared with those in mice given monotherapy. No overt toxicity was evident with any regimen. The mechanism of increased efficacy may be altered cilofungin distribution, excretion, or metabolism; antifungal synergy; or both. These results indicate that concurrent cilofungin-amphotericin B therapy has synergistic or additive efficacy in vivo. PMID- 1929291 TI - Influence of beta-lactamase inhibitors on the potency of their companion drug with organisms possessing class I enzymes. AB - The ability of beta-lactamase inhibitors to induce class I beta-lactamases in certain organisms in vitro suggests a potential for antagonism in vivo. Therefore, a study was designed to assess the ability of sulbactam and clavulanate to induce beta-lactamases in two strains each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Pseudomonas aeruginosa both in vitro and in vivo. Induction in vitro was observed only with S. marcescens and P. aeruginosa and generally only when inhibitor concentrations greater than 2 micrograms/ml were examined. A mouse model of lethal infection, designed to detect in vivo antagonism arising from beta-lactamase induction, was used to determine what effect sulbactam and clavulanate would have on the 50% protective doses (PD50s) of cefoperazone and ticarcillin. Antagonism (a significant increase in the PD50) was observed in only 4 of 32 tests. Three of these involved antagonism of cefoperazone by clavulanate, and one involved antagonism of cefoperazone by sulbactam. In 6 of 32 tests, enhancement of efficacy (a significant decrease in PD50) was observed. In four of these, sulbactam enhanced cefoperazone; in one, sulbactam enhanced ticarcillin; and in one, clavulanate enhanced ticarcillin. Four of the six cases of enhancement occurred when the beta-lactamase inhibitor was given at the time of challenge. None of these positive or negative in vivo effects were predicted by in vitro tests. These data suggest that beta-lactamase inhibitors can influence the in vivo potency of their companion drug in both a beneficial and detrimental fashion against organisms with class I beta-lactamases and that these effects cannot be predicted from in vitro assays. PMID- 1929292 TI - Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs. AB - Pneumocystis carinii was obtained in high yield from the lungs of immunosuppressed rats by rupturing mammalian host cells, washing away the soluble mammalian dihydrofolate reductase, and harvesting intact organisms in association with the mammalian plasma membranes. P. carinii dihydrofolate reductase, measured in the 100,000 x g supernatant from sonicated organisms, was obtained in yields ranging up to 62 IU per rat. The enzyme prepared in the presence of protease inhibitors was stable when frozen in liquid nitrogen. P. carinii dihydrofolate reductase differed from the mammalian enzyme in that the former was slightly inhibited by 150 mM KCl, whereas the latter was stimulated over twofold by 150 mM KCl. The standard assay for P. carinii dihydrofolate reductase contained 0.12 mM NADPH and 92 microM dihydrofolic acid. Under these conditions, the 50% inhibitory concentrations of the known inhibitors trimethoprim, trimetrexate, and pyrimethamine were 12 microM, 42 nM, and 3.8 microM, respectively. These standard compounds were also tested against dihydrofolate reductase from rat liver to allow an assessment of the selectivity of the drugs. Although it was the least potent, trimethoprim was the most selective. Pyrimethamine was more potent but was nonselective. Trimetrexate was extremely potent but was selective for mammalian dihydrofolate reductase. A series of experimental compounds was obtained from the National Cancer Institute and other sources through the Developmental Therapeutics Branch of the Division of AIDS at the National Institute of Allergy and Infectious Diseases. Among the first 87 compounds tested, 11 had 50% inhibitory concentrations below that of trimetrexate and 3 were more selective than trimethoprim. The most promising compounds in this original group were chemically related to methotrexate. PMID- 1929293 TI - Cefonicid versus clindamycin prophylaxis for head and neck surgery in a randomized, double-blind trial, with pharmacokinetic implications. AB - Perioperative single-dose antibiotic prophylaxis of cefonicid was compared with clindamycin in a prospective, randomized, double-blind trial of patients undergoing oncologic head and neck surgery. Antibiotics were administered intravenously beginning 1 to 2 h preoperatively. Cefonicid, 1 g, was given as a single dose. Clindamycin, 600 mg, was administered every 8 h for a total of four doses. Blood and wound drainage samples were collected for 24 h following the dose of cefonicid and assayed for total and free cefonicid concentrations, using reverse-phase high-performance liquid chromatography. Although total concentrations of cefonicid in both serum and wound drainage exceeded the MIC for 90% of the isolates of common bacterial pathogens for 24 h, free concentrations in serum and wound drainage (11.0 and 14.9% of total concentrations) were subinhibitory within 6 h following administration. Free concentrations of cefonicid in the postoperative wound drainage were subinhibitory for the entire study period, both perioperatively and postoperatively. Postoperative wound infection occurred significantly (P less than 0.05) more frequently in patients receiving cefonicid (24%) as compared with those receiving clindamycin (8.2%). The relatively low free levels of cefonicid achieved in serum and wound drainage were attributed to the high degree of protein binding (89% in serum) and may be related to the poor clinical outcome. PMID- 1929294 TI - Cardiovascular and autonomic pharmacology of the macrolide antibiotic LY281389 in anesthetized beagles and in isolated smooth and cardiac muscles. AB - As part of the preclinical safety evaluation process, an investigational macrolide antibiotic, LY281389, was examined for autonomic activity in isolated smooth and cardiac muscle preparations and for cardiovascular effects by intravenous infusion in anesthetized beagles. Concentration-dependent antagonism of acetylcholine and angiotensin I (guinea pig ileum), norepinephrine (rat vas deferens), and isoproterenol (guinea pig atria) was observed at LY281389 concentrations of greater than or equal to 10(-5) M. At LY281389 concentrations of greater than or equal to 10(-4) M, the response of the guinea pig ileum to electrical stimulation was also inhibited approximately 65 to 100%, indicative of potential anticholinergic or alpha-adrenergic activity. In anesthetized dogs, the predominant effect of LY281389 was an increase in heart rate at doses of greater than or equal to 200 micrograms/kg of body weight. LY281389 also produced slight increases in mean arterial pressure and shortening of the P-R interval of the electrocardiogram. In summary, LY281389 possesses nonselective receptor antagonist activity in vitro and produces cardiovascular stimulation in anesthetized dogs. These results indicate that, in addition to potent antimicrobial activity, the macrolide antibiotic LY281389 may exert unexpected actions on cardiovascular function. PMID- 1929295 TI - In vitro activity of YM133, a new semisynthesized macrolide. AB - YM133, the 4"-O-(4-methoxyphenyl)acetyltylosin, is a new macrolide. The in vitro activity of YM133 was compared with those of erythromycin, josamycin, and rokitamycin by an agar dilution method. YM133 inhibited 90% of the tested isolates of Streptococcus pneumoniae, Legionella spp., and anaerobic bacteria at less than or equal to 1.56 micrograms/ml. The drug inhibited 90% of erythromycin resistant staphylococci and Streptococcus pyogenes at less than or equal to 50 micrograms/ml. YM133 showed activity against erythromycin-, josamycin-, and rokitamycin-resistant (MIC greater than or equal to 100 micrograms/ml) strains of staphylococci, streptococci, Bacteroides spp., and Clostridium spp. Enterococci were less susceptible to other YM133-like macrolides. Unlike other macrolides, YM133 showed killing activity, and the MBC/MIC ratios of YM133 for several strains were 1:32, whereas those of erythromycin were 4:1,024. In a time-kill curve study, the reduction of viable cells started within 2 h after the addition of YM133. PMID- 1929296 TI - Pharmacokinetics of cefotaxime and desacetylcefotaxime in patients with liver disease. AB - The dispositions of cefotaxime and its metabolite desacetylcefotaxime were investigated in patients with different forms of chronic parenchymal liver disease (CPLD). A total of 31 subjects (27 patients and 4 controls) received a single 2-g dose of cefotaxime by infusion, and serial blood samples were drawn. The area under the concentration-time curve ranged from 176 to 241 micrograms.h/ml, the apparent half-life ranged from 1.49 to 2.42 h, and clearance ranged from 2.06 to 3.10 ml/min/kg in patients with four different forms of CPLD. The area under the concentration-time curve and the apparent half-life of desacetylcefotaxime ranged from 72 to 128 micrograms.h/ml and 7.1 to 13.4 h, respectively. Pharmacokinetic parameters were significantly different in patients with CPLD compared with those in control subjects and were related to clinical indices of hepatic impairment. Modest accumulation of cefotaxime in patients with severe hepatic impairment is unlikely to produce toxicity because of its high therapeutic index, and dosing modifications may not be required. PMID- 1929297 TI - Lytic effect of two fluoroquinolones, ofloxacin and pefloxacin, on Escherichia coli W7 and its consequences on peptidoglycan composition. AB - Examination of biochemical changes in Escherichia coli W7 after exposure to ofloxacin or pefloxacin revealed distinct concentration-dependent responses. At levels close to the MIC, extensive filamentation was followed by a lytic event, which involved an active protein synthesis. This lysis was correlated with changes in the peptidoglycan composition, particularly a decrease in the average glycan chain length, involving the action of the autolysines. At higher concentrations, no lysis occurred and the growth was totally inhibited as well as the protein synthesis. The peptidoglycan composition exhibited an increase in the average glycan chain length, suggesting an apparent reduced activity of the lytic transglycosylase. These results show that exposure to low concentrations of quinolones leads to the induction of lysis and peptidoglycan modifications which might contribute to the bactericidal effects of quinolones. PMID- 1929298 TI - Anti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2' deoxy-3'-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog. AB - We describe a novel nucleoside analog, 2'-deoxy-3'-thiacytidine (BCH-189), in which the 3' carbon of the ribose ring of 2'-deoxycytidine has been replaced by a sulfur atom. In MT-4 T cells, this compound had significant time- and dose dependent antiviral activity against five different strains of human immunodeficiency virus type 1 (HIV-1) (mean 50% inhibitory dose, 0.73 microM); known 3'-azido-3'-deoxythymidine (AZT)-resistant HIV-1 variants did not exhibit cross-resistance to it. BCH-189 also suppressed HIV-1 replication in the U937 monocytoid cell line as well as in primary cultures of human peripheral blood mononuclear cells; in these latter systems, suppression was fuller and longer lasting than that induced by AZT. Moreover, BCH-189 was less toxic than AZT in cell culture. BCH-189 may be a promising drug for the treatment of HIV-1 associated disease. PMID- 1929299 TI - Molecular distribution of ROB-1 beta-lactamase in Actinobacillus pleuropneumoniae. AB - The plasmid content and molecular distribution of the ROB-1 beta-lactamase was investigated in 31 swine isolates of Actinobacillus pleuropneumoniae. Three types of plasmid patterns were observed in ampicillin-resistant isolates: a predominant one consisting of 2.6-, 2.9-, and 5.0-kb plasmids and two other patterns consisting of 4.2- and 5.5-kb plasmids and of a 6.8-kb plasmid. Plasmid DNA preparations were hybridized with a blaROB-1 intragenic fragment from the Haemophilus influenzae Rrob plasmid. Positive hybridizations were observed with all ampicillin-resistant isolates. The blaROB-1 gene was found on 3 plasmids of 2.6, 5.5, and 6.8 kb. One swine isolate of Pasteurella multocida also had a 2.6 kb plasmid bearing blaROB-1. ROB-1 was confirmed in typical isolates by isoelectric focusing and blaROB-1 sequences were confirmed by polymerase chain reaction amplification with an intragenic set of primers. Plasmids bearing blaROB 1 were successfully electro-transformed in a susceptible A. pleuropneumoniae isolate. These results emphasize the importance of ROB-1 in A. pleuropneumoniae and identify a possible reservoir of beta-lactam resistance. PMID- 1929300 TI - Suppression of Leishmania donovani by oral administration of a bis(benzyl)polyamine analog. AB - We reported previously that intraperitoneal administration of a bis(benzyl)polyamine analog, MDL 27,695, suppressed both pentavalent antimony (Sbv)-susceptible and -resistant Leishmania donovani in vivo. The present studies were performed to optimize parasite suppression by parenteral administration and to evaluate the efficacy of oral treatment with MDL 27,695. L. donovani infections in BALB/c mice were suppressed greater than 99% after intraperitoneal dosing for 20 days with a total dose of 150 mg of MDL 27,695 per kg of body weight or 560 mg of Sbv per kg. Suppression was not increased by a total dose of 400 mg of MDL 27,695 per kg given for 20 days. In mice treated for 2, 4, or 7 days with either MDL 27,695 or Sbv (total doses of 60, 120, and 210 mg/kg, respectively), more liver parasites were killed with MDL 27,695 than with Sbv. Assessment of livers posttreatment showed that parasite killing continued for at least 3 days in MDL 27,695-treated mice but not for longer than 1 day in Sbv treated mice. Intramuscular administration of drugs resulted in 92% parasite suppression by MDL 27,695 (15 mg/kg three times per day for 5 days) and 64% suppression by Sbv (60 mg/kg once per day for 5 days). Dosing of mice by oral gavage with 100 mg of MDL 27,695 per kg twice per day for 14 days resulted in 99.7% parasite suppression, and the 50% effective dose was approximately 11 mg of MDL 27,695 per kg. MDL 27,695 represents an effective new drug potentially useful for oral or parenteral treatment of visceral leishmaniasis. PMID- 1929301 TI - Comparison of Enterococcus raffinosus with Enterococcus avium on the basis of penicillin susceptibility, penicillin-binding protein analysis, and high-level aminoglycoside resistance. AB - We reidentified our laboratories' collections of 57 enterococcal isolates previously classified as Enterococcus avium by the API Rapid Strep identification system (Analytab Products, Plainview, N.Y.) with the identification criteria recommended by Facklam and Collins (R. R. Facklam and M. D. Collins, J. Clin. Microbiol. 27: 731-734, 1989). Thirty isolates were identified as true E. avium, 25 isolates were identified as E. raffinosus, and 2 isolates were identified as E. pseudoavium. E. raffinosus could be differentiated from E. avium on the basis of penicillin susceptibility, as follows: MIC for 50% of E. raffinosus isolates tested (MIC50), 32 micrograms/ml; MIC90, 64 micrograms/ml (range, 4 to 64 micrograms/ml); E. avium MIC50, 1 microgram/ml; MIC90, 2 micrograms/ml (range, 0.5 to 2 micrograms/ml). No strains produced detectable beta-lactamase. Penicillin-binding protein (PBP) analysis of all E. raffinosus isolates demonstrated the unique pattern reported previously (M. D. Collins, R. R. Facklam, J. A. E. Farrow, and R. Williamson, FEMS Microbiol. Lett. 57:283-288, 1989); however, a number of newly identified PBPs were noted. Of 25 isolates, 13 had an additional PBP of 77 kDa (designated PBP 6*), while all isolates possessed a 52-kDa PBP (PBP 7) and a 46-kDa PBP (PBP 8). The presence or absence of PBP 6* did not correlate with penicillin susceptibility; however, PBP 7 demonstrated many features suggestive of low penicillin-binding affinity and may represent a possible mechanism for the relative resistance of this species to penicillin, although this hypothesis remains speculative since attempts to develop a penicillin-hypersusceptible E. raffinosus mutant were unsuccessful. E. raffinosus isolates were significantly more likely to exhibit high-level resistance to kanamycin than E. avium strains were (P < 0.001; chi-square); however, no strains demonstrated high-level resistance to gentamicin. No trend toward increasing penicillin resistance was noted among this collection of E. avium and E. raffinosus isolates collected over the past 35 and 14 years, respectively. Relative resistance to penicillin may be a helpful differentiating feature between E. avium and E. raffinosus when assessment of raffinose metabolism is not possible or is indeterminant. PMID- 1929303 TI - Bactericidal effects of ticarcillin-clavulanic acid against Legionella pneumophila pneumonia in immunocompromised weanling rats. AB - A model of acute Legionella pneumophila pneumonia in neutropenic weanling rats was developed as a means of assessing the efficacies in vivo of the beta-lactams ticarcillin, ticarcillin-clavulanic acid, and clavulanic acid, agents active against the organism in vitro. Weanling rats were dosed with cyclophosphamide 3 days before and immediately prior to infection by intrabronchial intubation with L. pneumophila. The bacteria persisted in the lungs of untreated animals at high counts (5.0 to 7.0 log10 CFU/g of lung tissue) for up to 168 h after infection, and the histological characteristics of the infection were similar to those of the disease in humans. Transmission electron micrography revealed the presence of L. pneumophila multiplying within alveolar macrophages. Therapy with ticarcillin was ineffective in reducing the bacterial numbers in the lung tissue, whereas ticarcillin-clavulanic acid and clavulanic acid were active, producing bactericidal effects similar to those of erythromycin. The ticarcillin-clavulanic acid combination was significantly more efficacious (P less than 0.01) than corresponding doses of clavulanic acid alone. Synergistic activity between ticarcillin and clavulanic acid against L. pneumophila has been demonstrated in vivo, and the combination showed activity similar to that of erythromycin. PMID- 1929302 TI - Correlation between in vitro and in vivo activity of antimicrobial agents against gram-negative bacilli in a murine infection model. AB - We studied the relationship between in vitro susceptibility tests (MICs, MBCs) and in vivo activity of tobramycin, pefloxacin, ceftazidime, and imipenem against 15 gram-negative bacilli from five different species in a murine thigh infection model. Complete dose-response curves were determined for each antimicrobial agent against each strain, and three parameters of in vivo activity were defined: maximal attainable antimicrobial effect (i.e., reduction in log10 CFU per thigh compared with untreated controls) at 24 h (Emax), total dose required to reach 50% of maximal effect (P50), and total dose required to achieve a bacteriostatic effect (static dose). Pefloxacin demonstrated the greatest Emax (P less than 0.05). Tobramycin was the most potent antimicrobial agent, as indicated by its having the lowest static dose/MIC ratio (P less than 0.002). Log10 P50s and static doses correlated significantly with log10 MICs or MBCs for the 15 strains of each antibiotic (P less than 0.01) except imipenem (P greater than 0.50). The greater potency of imipenem against the three Pseudomonas aeruginosa strains than against strains of the family Enterobacteriaceae (P less than 0.01) explained this lack of correlation. A longer duration of postantibiotic effect for imipenem against P. aeruginosa (P = 0.02) contributed to its increased potency against these strains. We conclude that in vitro susceptibility tests correlated well with in vivo activity in this animal model and that variations in potency among the four antimicrobial agents could be explained by differences in pharmacokinetics or pharmacodynamic activity. PMID- 1929304 TI - Synergistic inhibition of human immunodeficiency virus type 1 replication by 5 ethyl-1-ethoxymethyl-6-(phenylthio)uracil (E-EPU) and azidothymidine in vitro. AB - A novel 6-substituted acyclouridine derivative, 5-ethyl-1-ethoxymethyl-6 (phenylthio)uracil (E-EPU), has recently proved to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. Combinations of 3'-azido-2',3'-dideoxythymidine (AZT) and E-EPU synergistically inhibit the replication of HIV-1 in MT-4 cells, whereas the cytotoxic effects of AZT and E-EPU on mock-infected MT-4 cells are not enhanced by the drug combination. Synergistic inhibition of HIV-1 replication has also been observed in peripheral blood lymphocytes. These results indicate that the combination of AZT and E-EPU should be further pursued in the treatment of AIDS. PMID- 1929305 TI - Evaluation of the hepatotoxic potential of minocycline. AB - Minocycline (25 to 100 micrograms/g) dose dependently increased serum glutamic oxalacetic transaminase, urea, and bilirubin levels, and the hepatic triglyceride content in mice. In animals pretreated with phenobarbital to enhance minocycline metabolism, the effects on liver triglycerides were attenuated, while the changes in serum glutamic oxalacetic transaminase, urea, and bilirubin were enhanced. It is concluded that part of the toxic effects of minocycline may be produced by a metabolite of minocycline. PMID- 1929306 TI - Radiolabeling of Mycobacterium leprae lipids within schwannoma cells, a potential drug screening system. AB - This study describes a novel method which could be developed into a test system of evaluating the efficacy of antileprosy drugs. The method estimates incorporation of [14C]acetate into lipids of Mycobacterium leprae maintained within the 33B Schwannoma cell line. Schwannoma cell-resident M. leprae cells incorporated significant levels of radiolabel within their lipids during 12 days of incubation in vitro. This incorporation was markedly reduced by 5 micrograms of rifampin per ml (decrease, 81.62%); this decrease was observed within 24 h of addition of the drug. Dapsone also reduced the radiolabel incorporation into the lipids, but to a lesser extent (decrease, 27.58%). This system was also able to differentiate between rifampin-sensitive and -resistant strains of mycobacteria. It is suggested that since the effect of bacteriostatic (dapsone) and bactericidal (rifampin) drugs could be detected by using this technique, it may prove useful in screening novel drugs acting against M. leprae. PMID- 1929307 TI - Aerosol and intraperitoneal administration of ribavirin and ribavirin triacetate: pharmacokinetics and protection of mice against intracerebral infection with influenza A/WSN virus. AB - Ribavirin is active in vitro but not in vivo against a number of viruses capable of causing encephalitis. Ribavirin triacetate (RTA), a lipophilic derivative, has been reported to be more effective than ribavirin in protecting animals from encephalitis. By using an influenza A/WSN virus encephalitis model, we demonstrated that RTA administered by small-particle aerosol was able to decrease the death rate and increase the time of survival. To determine if this beneficial effect was due to increased delivery of drug, the pharmacokinetic properties of ribavirin and RTA when administered as an aerosol or by intraperitoneal injection were examined. Aerosol administration of ribavirin or RTA gave significantly higher concentrations of ribavirin in the lungs and serum of mice than did intraperitoneal injection. There was no difference, however, in ribavirin levels when either ribavirin or RTA was administered by small-particle aerosol. In brain tissue, ribavirin concentrations increased with time and did not appear to decrease as rapidly as in lungs and serum. Mean peak ribavirin concentrations in the brain were higher following aerosol administration of ribavirin than RTA, and both were higher than that following intraperitoneal injection of either drug. Administration of ribavirin or RTA by intraperitoneal injection failed to protect mice from a lethal intracerebral inoculation of influenza A/WSN virus, while aerosolized RTA did protect mice. The pharmacokinetics of ribavirin in brain tissue following aerosol administration of either drug did not explain the advantage of RTA over ribavirin in protecting mice from intracerebral infection with influenza A/WSN virus. PMID- 1929308 TI - Altered tobramycin pharmacokinetics during chemoprophylaxis in bladder surgery. AB - The effect of bladder surgery on the pharmacokinetics of tobramycin in hospitalized patients was studied. Fourteen patients with vesical neoplasia undergoing urinary tract surgery were given tobramycin in a dose of 2 mg/kg of body weight. Each patient received the dose at the induction of anesthesia, about 1 h before surgical incision. For seven patients, the drug was also administered 3 weeks later when nutritional conditions were normal. The pharmacokinetic parameters were determined by a two-compartment open model. Except for renal clearance, no significant difference appeared between pharmacokinetic parameters determined from serum data during peri- and postoperative periods. During this work, tobramycin excretion in urine was studied. Twenty-four hours after drug administration, the mean urine tobramycin levels were 25.5 +/- 9.06 and 41.6 +/- 21.5 micrograms/ml after peri- and postoperative administration, respectively; these values were higher than the MICs for most urinary tract pathogens. Seventy two hours after perioperative administration, the mean value was still elevated (3.54 micrograms/ml), but 72 h after postoperative administration, the urinary tobramycin concentration was not detectable. The percentages of tobramycin recovered unchanged in urine were 54 and 79% after peri- and postoperative administration, respectively. When tobramycin was administered during surgery, a long terminal log-linear phase, with a mean half-life of 25.6 h, was detected. The ratio of renal clearance to total body clearance was 0.52 and 0.79 after peri and postoperative administration, respectively. PMID- 1929309 TI - Treatment of experimental cryptococcosis with SCH 39304 and fluconazole. AB - The efficacy of two triazoles, SCH 39304 and fluconazole, in the treatment of disseminated cryptococcosis in Wistar rats was determined. A total of 160 rats were inoculated intracardiacally with 2 x 10(5) cells of Cryptococcus neoformans. Both drugs were administered by gavage once daily, at three doses (8, 16, and 32 mg/kg/day). Two treatment schedules were followed: (i) treatment began 1 week after infection and continued for 3 weeks and (ii) prophylaxis treatment began 3 days before infection and continued an additional 3 weeks. Evaluation was based on (i) macroscopic examination of lungs, (ii) microscopic examination of brains and lungs, (iii) histopathology of brains and lungs, and (iv) determination of number of CFU in brains. The number of CFU was the best measure of activity. SCH 39304 was more active than fluconazole in both regimens, and, prophylactically, SCH 39304 was able to achieve biological cures. PMID- 1929310 TI - Quinine uptake by human polymorphonuclear neutrophils. AB - The antimalarial drug quinine has been shown to impair human polymorphonuclear leukocyte (PMN) functions. To gain insight into the mechanism of this phenomenon, we investigated quinine uptake by PMN with a fluorometric assay based on the fluorescence properties of this drug. After 30 min of incubation at 37 degrees C in the presence of 1 and 10 micrograms of quinine per ml, PMN-associated quinine reached 90 +/- 6 and 780 +/- 150 ng/2.5 x 10(6) PMN, respectively, giving a cellular-to-extracellular concentration ratio of 140 to 150. A steady state was reached within 5 min. Uptake was partially dependent on temperature, cell viability, and extracellular pH. Fractionation studies showed that 30 to 40% of the PMN-associated quinine was located in the particulate fraction. The efflux of PMN-associated quinine was rapid and complete when the incubation mixture was replaced by drug-free medium. These data suggest that several mechanisms are involved in the uptake of quinine by PMN, including a viability- and energy independent process possibly related to reversible association of quinine to cell structures (particularly the membrane). Other mechanisms could involve trapping by protonation and/or active PMN transport systems. Thus, most of the quinine taken up by resting PMN is found in the soluble fraction of disrupted cells. This may partly explain the depressive properties of quinine. PMID- 1929311 TI - Single-dose and three-day regimens of ofloxacin versus trimethoprim sulfamethoxazole for acute cystitis in women. AB - We compared the safety and efficacy of a single 400-mg dose of ofloxacin, ofloxacin (200 mg) once daily for 3 days, and trimethoprim-sulfamethoxazole (160:800 mg) twice daily for 7 days for the treatment of acute uncomplicated cystitis (urinary tract infection [UTI]) in women. At 5 weeks posttreatment, 35 (81%) of 43 patients treated with single-dose ofloxacin, 40 (89%) of 45 treated with 3 days of ofloxacin, and 41 (98%) of 42 treated with trimethoprim sulfamethoxazole were cured (P = 0.03, single-dose ofloxacin group versus trimethoprim-sulfamethoxazole group). Retreatment for symptomatic recurrent UTI was given to 7 (16%) of 43 patients initially treated with single-dose ofloxacin, 3 (7%) of 45 patients treated with 3 days of ofloxacin, and 0 of 42 patients treated with trimethoprim-sulfamethoxazole (P = 0.01, single-dose ofloxacin group versus trimethoprim-sulfamethoxazole group). There was a trend in each of the three treatment groups toward an association between persistent or recurrent episodes of significant bacteriuria and a history of UTI in the past year and with diaphragm use. Ofloxacin was more effective than trimethoprim sulfamethoxazole in eradicating Escherichia coli from rectal cultures during or soon after therapy, but there were no differences at later follow-up visits. Adverse effects were equally common among the three treatment groups. We conclude that single-dose ofloxacin was less effective than 7 days of trimethoprim sulfamethoxazole for treatment of uncomplicated cystitis in women, while the 3 day ofloxacin regimen and the trimethoprim-sulfamethoxazole regimen were not significantly different in efficacy. PMID- 1929312 TI - Effects of enzyme supplementation on oral absorption of ciprofloxacin in patients with cystic fibrosis. AB - The effect of pancreatic enzyme supplementation on the absorption of an oral dose of 250 mg of ciprofloxacin was studied in six patients with cystic fibrosis in a crossover design. The time to achieve maximum serum concentration was slightly reduced upon coadministration of pancreatic enzymes. There were no significant differences in peak concentration, elimination half-life, and area under the concentration-time curve. PMID- 1929313 TI - Measurement of the concentration of amphotericin B in brain tissue of scrapie infected hamsters with a simple and sensitive method. AB - A simple, sensitive, and reproducible assay for the measurement of the amphotericin B concentration in tissue extracts was developed by using the fourth derivative of the absorption spectrum of amphotericin B between wavelengths of 330 and 430 nm. The amphotericin B concentration in spleen and brain was proportional to the total amount administered. The amphotericin B concentration in the brain was highly correlated with the increase in the mean incubation period of intracerebrally scrapie-infected hamsters. PMID- 1929314 TI - Pharmacokinetics of single-dose intravenous, oral, and intraperitoneal pefloxacin in patients on chronic ambulatory peritoneal dialysis. AB - Comparison of plasma and dialysate concentrations of pefloxacin after intravenous, oral, or intraperitoneal administration shows excellent bidirectional diffusion of the quinolone through the peritoneal membrane, demonstrating that therapeutical concentrations can be achieved in the dialysate after intravenous or oral administration. In this study, the half-life of the drug was 18.8 +/- 1.4 h, i.e., apparently longer than that reported for normal controls or uremic patients on hemodialysis. PMID- 1929315 TI - Failure of routine susceptibility tests to detect imipenem resistance among strains of methicillin-resistant Staphylococcus aureus. AB - We tested 75 methicillin-resistant Staphylococcus aureus strains for susceptibility to imipenem by using disk diffusion tests and broth microdilution tests with standard and heavy inocula. Population analysis was performed on isolates that appeared to be susceptible by these methods. All of the strains contained subpopulations of cells that are phenotypically resistant to imipenem. PMID- 1929316 TI - Identification of CTX-2, a novel cefotaximase from a Salmonella mbandaka isolate. AB - A strain of Salmonella mbandaka isolated from the feces of an Algerian infant showed a reduced susceptibility to cefotaxime (MIC, 8 mg/liter). This strain produced two transferable beta-lactamases of pIs 5.3 and 5.6. The novel beta lactamase with a pI of 5.3 inhibited by clavulanic acid showed cefotaxime hydrolysis and was therefore designated CTX-2. PMID- 1929318 TI - In vitro activity of loracarbef (LY163892), a new oral carbacephem antimicrobial agent, against respiratory isolates of Haemophilus influenzae and Moraxella catarrhalis. AB - The in vitro activity of a new orally administered carbacephem analog of cefaclor, loracarbef (LY163892), was compared with those of cefaclor and several other oral antimicrobial agents against recent clinical isolates of Haemophilus influenzae and Moraxella catarrhalis. Loracarbef was found to be slightly more active than cefaclor against H. influenzae and had activity essentially equivalent to that of cefaclor for M. catarrhalis. Resistance to loracarbef was uncommon and was noted only with rare beta-lactamase-producing strains of H. influenzae. On the basis of these observations, loracarbef may be of utility in the management of localized, non-life-threatening infections caused by H. influenzae and M. catarrhalis. PMID- 1929317 TI - Gentamicin pharmacokinetics in patients with malignancies. AB - The pharmacokinetics of gentamicin were investigated in 880 patients with leukemia (24 patients), other malignancies (211 patients), or no malignancies (645 patients) by using data collected by our Clinical Pharmacy Service. A significant difference was seen in the initial calculated creatinine clearance between the patients with leukemia and the other two groups. No differences in gentamicin pharmacokinetics were seen in patients with other malignancies versus those with no malignancies. Patients with leukemia had significantly faster drug clearance compared with those in the other two groups. A poor predictive value was found for total body clearance of gentamicin versus the initial calculated creatinine clearance in all groups. Multiple logistic regression analysis showed that only the initial calculated creatinine clearance differed in the leukemic group compared with those in the other patients. Our data suggest that no pharmacokinetic difference exists for gentamicin in patients with malignancies. PMID- 1929319 TI - In vitro comparison of GR69153, a novel catechol-substituted cephalosporin, with ceftazidime and ceftriaxone against 5,203 recent clinical isolates. AB - The activity of GR69153, a novel catechol-substituted cephalosporin, was compared with those of ceftazidime and ceftriaxone in a multicenter study against 5,203 fresh clinical isolates of gram-negative and gram-positive bacteria. GR69153 was generally very active at concentrations equivalent to or two- to fourfold lower than those of ceftazidime and ceftriaxone against gram-negative bacilli other than Citrobacter freundii, Enterobacter cloacae, and Xanthomonas maltophilia. Against Pseudomonas aeruginosa, MICs of GR69153 and ceftazidime for 50% of isolates tested (MIC50s) were, respectively, 1 and 2 micrograms/ml; the corresponding MIC90s were 4 and 16 micrograms/ml. Although MIC50s of GR69153 for staphylococci were two- to eightfold lower than those of ceftazidime or ceftriaxone, MIC90s against staphylococci and enterococci were greater than or equal to 16 micrograms/ml for all three compounds. Quality control MIC ranges for reference strains are proposed for the broth microdilution method on the basis of the GR69153 data derived from this multicenter study. PMID- 1929320 TI - Susceptibilities of Mycoplasma hominis and Ureaplasma urealyticum to two new quinolones, sparfloxacin and WIN 57273. AB - Mycoplasma hominis was highly susceptible to two new quinolones, with MICs for 90% of isolates tested of 0.004 micrograms/ml for WIN 57273 and 0.063 micrograms/ml for sparfloxacin, which were activities much greater than the 1 microgram/ml found for ofloxacin and tetracycline. Although Ureaplasma urealyticum was less susceptible, the MICs for 90% of isolates tested of 0.25 micrograms/ml for WIN 57273 and 0.5 micrograms/ml for sparfloxacin were four- to eightfold greater than those found for ofloxacin (2 micrograms/ml) and tetracycline (2 micrograms/ml). The finding that U. urealyticum and M. hominis are more susceptible to WIN 57273 and sparfloxacin than they are to other quinolones suggests that these quinolones may be therapeutically useful. PMID- 1929321 TI - Comparative study of various hydrogen ion buffers to assay Zn(2+)-dependent beta lactamases. AB - The low Zn2+ complex formation constants, the capacity to degrade penicillin G in combination with Zn2+, and UV absorbance make 4-(2-hydroxyethyl)-1 piperazineethanesulfonic acid, 3-[N-tris(hydroxymethyl)methylamino]-2 hydroxypropanesulfonic acid, 1,3-bis[tris(hydroxymethyl)methylamino]propane, and 1,4-piperazinediethanesulfonic acid convenient buffers to study Zn(2+)-dependent beta-lactamases. PMID- 1929322 TI - Inhibition of Cryptosporidium parvum in neonatal Hsd:(ICR)BR Swiss miceby polyether ionophores and aromatic amidines. AB - Cryptosporidicidal effects of two polyether ionophores (maduramicin and alborixin), a fluorinated 4-quinolone (enrofloxacin), and three analogs of pentamidine were evaluated in a suckling mouse bioassay. Treatment with all compounds except enrofloxacin and one of the pentamidine analogs [1,3-di(4 imidazolinophenoxy)propane] resulted in significant (P less than 0.05) reductions in oocyst excretion. PMID- 1929323 TI - Animal models in the evaluation of antimicrobial agents. PMID- 1929324 TI - Physiological effects of fenpropimorph on wild-type Saccharomyces cerevisiae and fenpropimorph-resistant mutants. AB - Fenpropimorph-resistant mutants of Saccharomyces cerevisiae were isolated by a gradient selection procedure. The mutants were cross-resistant to other morpholines (fenpropidin, dodemorph, tridemorph) and 15-azasterol, but were susceptible to azoles (miconazole, clotrimazole, ketoconazole) and nystatin. In the absence of fenpropimorph, the major sterol produced by the mutants and the parental strain was ergosterol. In the presence of fenpropimorph, ignosterol (ergosta-8,14-dien-3 beta-ol) was the major sterol produced by the mutants and the parental strain. The resistance to fenpropimorph involves two recessive genes, each of which allows a semiresistance, when they are isolated apart from one another. Strain JR4 (erg3 erg11), which produces 14-methylfecosterol [14 alpha-methyl-ergosta-8,24(28)-dien- 3-beta-ol) as the major sterol in the presence or absence of fenpropimorph, was also found to be resistant to the drug. The growth inhibitory effect of fenpropimorph on wild-type cells appears to be linked to the production of ignosterol. The uptake of exogenous sterol by wild type cells was greatly enhanced in the presence of fenpropimorph. The growth inhibition caused by fenpropimorph could only be overcome with bulk levels of exogenous C-5,6-unsaturated sterols. PMID- 1929325 TI - Development of resistance to fleroxacin during therapy of experimental methicillin-susceptible Staphylococcus aureus endocarditis. AB - The efficacy of fleroxacin was compared with that of vancomycin by using the rabbit model of methicillin-susceptible Staphylococcus aureus endocarditis. Animals received intravenous therapy with fleroxacin, 30 mg/kg every 8 h, or vancomycin, 17.5 mg/kg every 6 h, for 4 days. Both antimicrobial agents effectively cleared bacteremia and significantly reduced bacterial counts in vegetations and tissues compared with those in untreated controls. However, resistance to fleroxacin at 5- and 10-fold the MIC arose in the test strain of S. aureus in 73 and 27%, respectively, of animals that received the drug. Resistant isolates were found mainly in vegetations and were composed of up to 7% of the residual population recovered from that site. We conclude that fleroxacin is as effective as vancomycin in this model of a serious systemic S. aureus infection, but resistance to the drug may develop during therapy. If similar results are found with other strains of S. aureus during therapy with this or other fluoroquinolones, such data, when they are combined with the high incidence of fluoroquinolone resistance among S. aureus isolates being reported from selected institutions, would support the contention that these drugs should not be used as first-line therapeutic agents for S. aureus infections. PMID- 1929326 TI - Nucleotide sequence and phylogeny of a chloramphenicol acetyltransferase encoded by the plasmid pSCS7 from Staphylococcus aureus. AB - The nucleotide sequence of the chloramphenicol acetyltransferase gene (cat) and its regulatory region, encoded by the plasmid pSCS7 from Staphylococcus aureus, was determined. The structural cat gene encoded a protein of 209 amino acids, which represented one monomer of the enzyme chloramphenicol acetyltransferase (CAT). Comparisons between the amino acid sequences of the pSCS7-encoded CAT from S. aureus and the previously sequenced CAT variants from S. aureus, Staphylococcus intermedius, Staphylococcus haemolyticus, Bacillus pumilis, Clostridium difficile, Clostridium perfringens, Escherichia coli, Shigella flexneri, and Proteus mirabilis were performed. An alignment of CAT amino acid sequences demonstrated the presence of 34 conserved amino acids among all CAT variants. These conserved residues were considered for their possible roles in the structure and function of CAT. On the basis of the alignment, a phylogenetic tree was constructed. It demonstrated relatively large evolutionary distances between the CAT variants of enteric bacteria, Clostridium, Bacillus, and Staphylococcus species. PMID- 1929327 TI - Synergistic activity of 5-trifluoromethylthioribose and inhibitors of methionine synthesis against Klebsiella pneumoniae. AB - 5-Methylthioribose (MTR) is an intermediate in the methionine recycling pathway of organisms containing the enzyme MTR kinase. Analogs of MTR have been proposed as a new class of antimicrobial agents because of their ability to perturb the growth of MTR kinase-containing pathogens through inhibition of methionine salvage or by conversion to toxic products. One such analog, 5 trifluoromethylthioribose (TFMTR), has demonstrated potent inhibitory effects on the growth of Klebsiella pneumoniae (A. G. Gianotti, P. A. Tower, J. H. Sheley, P. A. Conte, C. Spiro, J. H. Fitchen, and M. K. Riscoe, J. Biol. Chem. 265:831 837, 1990). Although the mode of action of TFMTR has yet to be determined, it is believed that the drug is converted to the toxic products trifluoromethionine or carbonothioic difluoride via MTR kinase and the methionine recycling pathway. On the basis of this assumption, we theorized that blocking de novo methionine synthesis would increase dependence on the methionine salvage pathway and lead to an increased rate of synthesis of toxic metabolites from TFMTR. In this report, we show that three separate inhibitors of de novo methionine synthesis (1,2,4 triazole, azaserine, and propargylglycine) act synergistically with TFMTR in inhibiting the growth of K. pneumoniae. PMID- 1929328 TI - Translocation of antibiotic resistance determinants including an extended spectrum beta-lactamase between conjugative plasmids of Klebsiella pneumoniae and Escherichia coli. AB - The extended-spectrum beta-lactamase CAZ-7, derived from TEMs, was produced by two different strains of the family Enterobacteriaceae, Klebsiella pneumoniae and Escherichia coli, isolated from the same patient. Both isolates were resistant to amikacin. In addition, the K. pneumoniae strain was TEM-1 producing and resistant to gentamicin. An E. coli HB101 transconjugant obtained from K. pneumoniae, selected on ceftazidime, showed that CAZ-7 and amikacin resistance were encoded by an 85-kb Inc7 or M plasmid, while an E. coli HB101 transconjugant obtained from E. coli under the same conditions showed that CAZ-7 and amikacin resistance were encoded by a greater than 150-kb Inc6 or C plasmid. Two other E. coli HB101 transconjugants obtained from K. pneumoniae, selected on gentamicin or chloramphenicol, showed that TEM-1 and gentamicin resistance could be encoded either by a greater than 150-kb Inc6 or C plasmid or by an 85-kb Inc7 or M plasmid. It was hypothesized that the genes for beta-lactam and aminoglycoside resistances were located on translocatable sequences. EcoRI digestion and hybridizations obtained with blatem, aacA4, and IS15 probes demonstrated that the CAZ-7 gene, amikacin resistance gene, and IS15 element were clustered on an approximately 20-kb fragment common to 85- and greater than 150-kb plasmids. E. coli HB101 transconjugants from K. pneumoniae and E. coli isolates were used to obtain translocations of CAZ-7 and amikacin resistance and of TEM-1 and gentamicin resistance between the 85- and greater than 150-kb plasmids. This study shows a typical example of in vivo gene dissemination involving transposable elements which translocate multiresistance genes, including an extended-spectrum beta-lactamase. PMID- 1929329 TI - Ofloxacin pharmacokinetics in mechanically ventilated patients. AB - The pharmacokinetics of ofloxacin were studied in 12 intensive care patients, 6 of whom were under controlled mechanical ventilation. All patients had a creatinine clearance of greater than 80 ml/min per 1.73 m2. They were given 3 mg of ofloxacin per kg of body weight intravenously at a constant flow rate in 30 min twice a day for 7 days. Pharmacokinetic studies were performed on days 1 and 7. Between days 1 and 7, significant increases in the alpha (distribution) and beta (elimination) phase half-lives, the area under the serum concentration-time curve, and peak and trough levels in serum were observed, together with a marked decrease (greater than 50%) in total body clearance. Possible contributing factors for alteration of ofloxacin pharmacokinetics in ventilated patients were patient age, liver dysfunction, drug interaction, and drug accumulation in a deep compartment. This study shows that in intensive care patients the pharmacokinetics of ofloxacin differ from those reported for healthy volunteers. PMID- 1929330 TI - Structural requirements of tetracycline-Tet repressor interaction: determination of equilibrium binding constants for tetracycline analogs with the Tet repressor. AB - We used the Tn10-encoded Tet repressor, which has a highly specific binding capacity for tetracycline, to probe contacts between the drug and protein by chemical interference studies of the antibiotic. For that purpose, the equilibrium association constants of modified tetracyclines with the Tet repressor and Mg2+ cations were determined quantitatively. The results confirm the previous notion that Mg2+ probably binds with the oxygens at positions 11 and 12 and is absolutely required for protein-drug recognition. Modifications were introduced at positions seven, six, five, and four of the drug, and anhydrotetracycline was also studied. Substitutions or eliminations of functions at these positions influenced binding to the Tet repressor up to 35-fold. The introduction of an azido function at position seven in 7-azidotetracycline and epimerization of the substituents at position four in 4-epitetracycline lead to a 2- or 25-fold reduction, respectively, of Tet repressor affinity in those compounds. Anhydrotetracycline bound about 35-fold more strongly than tetracycline did, indicating that the oxygen at position 11 may be involved in Tet repressor recognition. This increased binding is in contrast to the lower antibiotic activity of anhydrotetracycline and indicates that the Tet repressor and ribosomes recognize the drug differently. PMID- 1929331 TI - Prolonged and potent therapeutic and prophylactic effects of (S)-1-[(3-hydroxy-2 phosphonylmethoxy)propyl]cytosine against herpes simplex virus type 2 infections in mice. AB - The acyclic nucleotide analog (S)-1-[(3-hydroxy-2 phosphonylmethoxy)propyl]cytosine (HPMPC) is a potent and selective inhibitor of herpesviruses. Cells preincubated with HPMPC are refractory to herpes simplex virus type 2 (HSV-2) infection for several days after removal of the drug from the medium. A single administration of 30 mg of HPMPC per kg of body weight 4 days prior to virus infection intraperitoneally with HSV-2 (strain G) completely protected mice from death, and the protective effect was dose dependent. HPMPC was equally efficacious in protecting mice when the same total amount of the drug was administered as a single dose as when it was given daily in several smaller doses (5 mg/kg with treatment initiation at 3 h postinfection [p.i.], 90 versus 80% survival, respectively). In contrast, ganciclovir [9(1,3-dihydroxy-2 propoxymethyl)guanine] was more efficacious when it was given daily than it was when it was given less than daily in a late stage of HSV-2 infection (100 mg/kg; when mice were treated 96 h p.i., 80 versus 50% survival, respectively; when mice were treated 120 h p.i., 60 versus 20% survival, respectively). Therefore, single doses of HPMPC were more effective than ganciclovir in protecting mice from death (80 versus 20% survival, respectively; P less than 0.05), whereas there was no difference when the drugs were given daily (50 versus 60% survival, respectively). Our studies suggest a potential of HPMPC for conventional and prophylactic treatments of herpesvirus infections with infrequent drug administration. PMID- 1929332 TI - Role of intestinal excretion in the effect of subcutaneously administered sedecamycin on cecal infection caused by Treponema hyodysenteriae in mice. AB - The therapeutic effects of subcutaneously administered sedecamycin on experimental Treponema hyodysenteriae infection in mice were evaluated. Sedecamycin was more active than tiamulin and lincomycin. The efficacy of sedecamycin upon subcutaneous administration was similar to that upon oral administration. Sedecamycin given subcutaneously provided similar degrees of protection in bile duct-ligated and intact mice. Pharmacokinetic studies utilizing a liquid chromatographic technique were carried out to determine the concentration of sedecamycin in the cecum, the site of T. hyodysenteriae infection in mice. Little sedecamycin was found; however, lankacidinol, a major metabolite of sedecamycin, was found in the cecal contents of intact mice after subcutaneous or oral administration of sedecamycin. Lankacidinol was also found in the cecal contents of bile duct-ligated mice, although the concentration found after subcutaneous administration of sedecamycin was much lower than that found after subcutaneous or oral administration to intact mice. These results indicate that sedecamycin is excreted directly into the intestinal tract as an active metabolite by a route other than the bile duct. It is suggested that this intestinal excretion plays an important role in the efficacy of subcutaneously administered sedecamycin against cecal infection of mice by T. hyodysenteriae. PMID- 1929333 TI - Eradication of colonization by methicillin-resistant Staphylococcus aureus by using oral minocycline-rifampin and topical mupirocin. AB - In an attempt to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) within a spinal cord injury unit, we investigated the mode of transmission and implemented a multidisciplinary approach for control that consisted of grouping of patients into cohorts, contact isolation, and antibiotics. Surveillance cultures of patients and nose and hand cultures of medical personnel were performed. Of 11 colonized patients, 6 had MRSA isolates that shared a similar plasmid profile and antibiogram, raising the possibility of interpatient spread of the organism. Medical personnel had no evident role in transmitting MRSA. All patients' pretherapy MRSA isolates were susceptible to minocycline and, except for one, to rifampin. Time-kill studies showed an indifferent interaction of these two antibiotics. Ten colonized patients received a 2-week oral course of 100 mg of minocycline twice daily and 600 mg of rifampin once daily, while the 11th patient was treated for only 1 week. Patients with colonization of the nares also had twice daily nasal application of 2% mupirocin for 5 days. Colonization with MRSA cleared in 10 of 11 patients (91%) and 20 of 21 sites (95%). When the individual circumstances of a medical facility justify eradication of MRSA colonization, a multidisciplinary approach that includes antibiotic therapy with oral minocycline and rifampin, along with topical mupirocin for those with nasal carriage, may be successful. PMID- 1929334 TI - Removal of imipenem and cilastatin by hemodialysis in patients with end-stage renal failure. AB - The removal of imipenem and cilastatin by hemodialysis was studied in 14 (for imipenem) and 6 (for cilastatin) subjects. Following intravenous infusion of imipenem and cilastatin at a combined concentration of 10 mg/kg of body weight, drug levels in plasma were determined serially during off- and on-hemodialysis periods, which were 2 and 4 h, respectively. The biexponential decay of the drug levels in plasma was evident in each subject for both imipenem and cilastatin. Hemodialysis accelerated the elimination of both imipenem and cilastatin: the mean elimination-phase half-life of imipenem was shortened from 200 to 78 min, and that of cilastatin was shortened from 445 to 115 min. Hemodialysis clearance of imipenem and cilastatin was calculated by five different methods, each with intrinsic assumptions. The mean hemodialysis clearance of imipenem was estimated to be 74.08 +/- 13.29 ml/min, and that of cilastatin was estimated to be 65.0 +/- 8.6 ml/min, after consideration of various methodological limitations. It was estimated that in a hypothetical anephric patient weighing 60 kg, a 4-h hemodialysis treatment would remove 54.8% of the imipenem and 62.9% of the cilastatin present in the body at the start of dialysis. PMID- 1929335 TI - Effects of antimicrobial agents on survival of Mycobacterium avium complex inside alveolar macrophages obtained from patients with human immunodeficiency virus infection. AB - Measurements of the activities of antimicrobial agents against the Mycobacterium avium complex (MAC) usually do not take into consideration the intracellular location of the organism. A recent study using mouse macrophage continuous cell line J774 (D. M. Yajko, P.S. Nassos, C. A. Sanders, and W. K. Hadley, Am. Rev. Respir. Dis. 140: 1198-1203, 1989) showed that certain combinations of antimicrobial agents are able to kill MAC inside macrophages and suggested that the J774 cell line could be used as a model for screening of drugs for intracellular activity against MAC. As a test of the validity of this model, alveolar macrophages were isolated from the bronchoalveolar lavages of 36 patients who had AIDS or an AIDS-related condition or were considered to be at risk for AIDS. The macrophages were infected with MAC and then treated with a drug or drug combination for 48 to 72 h. Survival of MAC was measured over time in drug-treated macrophages and untreated control macrophages. No single drug or two-drug combination that was tested was able to cause a decrease in the survival of every one of the MAC strains used in the study. However, several three-drug combinations that had been shown to cause a decrease in survival of all MAC strains inside J774 cells also caused a decrease in survival of all MAC strains inside alveolar macrophages from patients. The good agreement between these results and those obtained previously with J774 cells gives further evidence of the usefulness of the simpler J774 model for screening of drugs for intracellular activity against MAC. PMID- 1929337 TI - Treatment of acute pelvic inflammatory disease in the ambulatory setting: trial of cefoxitin and doxycycline versus ampicillin-sulbactam. AB - Ampicillin-sulbactam (750 mg) given orally twice daily for 10 days was evaluated for the treatment of acute pelvic inflammatory disease (PID) in an ambulatory setting in Nairobi, Kenya. The first 26 women received ampicillin-sulbactam in an open-label fashion, and the remaining 75 women were randomly selected to receive either ampicillin-sulbactam (n = 38) or cefoxitin (2 g) intramuscularly and probenecid (1 g) orally, followed by doxycycline (100 mg) orally twice daily for 10 days (n = 37). Women were enrolled in a sexually transmitted disease clinic and were followed for clinical and microbiologic responses at 1 to 2 weeks and 4 to 6 weeks posttreatment. Women had a later follow-up visit to note interim pregnancy or underwent hysterosalpingography for fertility outcome assessment. The short-term clinical response rates were 70% for ampicillin-sulbactam and 72% for cefoxitin-doxycycline (P = 0.47). Among Chlamydia trachomatis-infected women treated with ampicillin-sulbactam, three had microbiologic relapse. The post-PID tubal obstruction rates were similar in the two groups: 18% for ampicillin sulbactam and 33% for cefoxitin-doxycycline (P = 0.31). Neither regimen was highly effective as a therapy for acute PID. These data strongly argue that primary prevention must be the goal for a reduction of PID morbidity and show that improved therapy for the treatment of PID in the ambulatory setting is needed. PMID- 1929336 TI - Bacteremia caused by hemolytic, high-level gentamicin-resistant Enterococcus faecalis. AB - Between 1 January 1984 and 31 December 1987, 206 enterococcal blood isolates at the University of Wisconsin Hospital and Clinics were analyzed for high-level aminoglycoside resistance (hereafter high-level aminoglycoside resistance is simply referred to as "resistance") and hemolysin production. Of 190 Enterococcus faecalis isolates, 68 (35.8%) were resistant to gentamicin. Of these 68 strains, 67 (98.5%) contained a gene coding for the bifunctional aminoglycoside-modifying 6'-aminoglycoside acetyltransferase-2"-aminoglycoside phosphotransferase [AAC(6') APH(2")] enzyme. Of 190 isolates, 85 (44.7%) were hemolytic and contained a gene coding for component A of the enterococcal hemolysin. Sixty-two of 68 (91.2%) gentamicin-resistant isolates but only 23 of 122 (18.8%) gentamicin-susceptible isolates were hemolytic (P less than 0.001). Twelve of the hemolytic, gentamicin resistant E. faecalis blood isolates, but only 2 of 9 nonhemolytic or gentamicin susceptible isolates, had identical chromosomal DNA restriction endonuclease digestion patterns, suggesting a common derivation for these strains. A historical cohort study from 1 July 1985 to 31 March 1987 identified by regression analysis postsurgical intensive care unit status (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.1 to 22.8) and prior treatment with an expanded- or broad-spectrum cephalosporin (OR, 3.0; 95% CI, 0.9 to 10.1) as risk factors for gentamicin-resistant E. faecalis bacteremia. Patients with hemolytic, gentamicin-resistant E. faecalis bacteremia had a fivefold-increased risk for death within 3 weeks of their bacteremia compared with patients with nonhemolytic, gentamicin-susceptible strains (95% CI, 1.0 to 25.4). PMID- 1929338 TI - Isoniazid protects mice against endotoxin lethality without influencing tumor necrosis factor synthesis and release. AB - Treatment of NMRI mice with isoniazid (INH; 25 mg/kg) intraperitoneally induced significant protection when it was injected before or after a lethal intravenous challenge with endotoxin. The INH preparation used was not contaminated with endotoxin. Tumor necrosis factor (TNF) was not elevated in sera from NMRI mice 2 h after the injection of INH. INH did not influence TNF synthesis or release determined in human monocytes in vitro. Therefore, it is concluded that the protective effect of INH against lethal endotoxin is not due to a suppressive effect of INH on TNF production. PMID- 1929339 TI - Interactions of amphotericin B and SCH 39304 in the treatment of experimental murine candidiasis: lack of antagonism of a polyene-azole combination. AB - Mice infected intravenously with Candida albicans were treated with SCH 39304, a new triazole antifungal compound, amphotericin B, or both. Two dose levels of each drug were evaluated in an attempt to identify potential helpful or harmful effects on survival and kidney colony counts. Contrary to theoretical predictions, combination therapy was not antagonistic and some additive or synergistic effects were observed. The results obtained in this study suggest that antagonism between polyene and azole antifungal drugs is not inevitable and that additive or synergistic effects may be possible. PMID- 1929340 TI - Antibody responses to in vitro translation products following albendazole therapy for Echinococcus granulosus. AB - Immunoprecipitation of antigens translated in vitro from Echinococcus granulosus RNA revealed that albendazole treatment of human hydatidosis induced antibodies to previously undetectable antigens and that the response to most antigens was specific, although cross-reactivity was observed between Schistosoma mansoni and E. granulosus antisera for two proteins. PMID- 1929341 TI - Tetracycline resistance in Peptostreptococcus species. AB - Of 15 Peptostreptococcus sp. strains isolated between 1975 and 1984, 13 hybridized with the Tet K, Tet M, or Tet O determinant. A donor Peptostreptococcus anaerobius strain carrying the three determinants could transfer Tet M to P. anaerobius and Fusobacterium nucleatum recipients but not to an Enterococcus faecalis recipient, while neither Tet K nor Tet O was transferred. PMID- 1929342 TI - Ofloxacin and penicillin G combination therapy in prevention of bacterial translocation and animal mortality after irradiation. AB - The efficacies of 40 mg of ofloxacin per kg/day given orally and 250 mg of penicillin per kg/day given intramuscularly, alone or in combination, were evaluated in the prevention of mortality of C3H/HeN female mice given 8.2 Gy of 60Co radiation. Mortalities were 51 of 60 mice (85%) in the control group, 46 of 60 mice (77%) among those treated with penicillin, 32 of 60 mice (53%) among those treated with ofloxacin (P less than 0.05), and 5 of 60 mice (8%) among those treated with ofloxacin and penicillin (P less than 0.001). The organisms recovered from the livers of control mice were members of the family Enterobacteriaceae and Streptococcus spp. A reduction in the number of the Enterobacteriaceae was noted only in ofloxacin-treated mice, and a reduction in the number of Streptococcus spp. was noted only in the penicillin-treated mice. Reductions in the numbers of both groups of organisms were noted only in the animals treated with both agents. This study shows the advantage of the combination of ofloxacin and penicillin in the prevention of bacterial translocation and animal mortality after irradiation. PMID- 1929343 TI - Comparison of single-dose administration and three-day course of amoxicillin with those of clavulanic acid for treatment of uncomplicated urinary tract infection in women. AB - In a double-blind randomized study we compared a single-dose amoxicillin clavulanate combination with a regular 3-day regimen in 109 women with cystitis. Clinical cure rates at 7 and 28 days posttreatment were 78 versus 87% and 67 versus 78%, respectively. The 3-day regimen was significantly better (P less than 0.001) only in women with recurrent urinary tract infections. PMID- 1929344 TI - In vitro antibacterial activity of ME1207, a new oral cephalosporin. AB - ME1207 is the prodrug of ME1206. Its in vitro antibacterial activity was compared with that of cefteram, cefpodoxime, cefixime, and cefaclor against various clinical isolates. ME1206 was more active than the other cephems tested against staphylococci, streptococci, Morganella morganii, Pseudomonas cepacia, and Flavobacterium meningosepticum and had the most potent activity against Haemophilus influenzae and Neiserria gonorrhoeae. The drug also showed a wide spectrum of activity against other gram-positive and gram-negative bacteria, except methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Citrobacter freundii, Pseudomonas aeruginosa, Xanthomonas maltophilia, and Alcaligenes xylosoxydans. PMID- 1929345 TI - Additional information on electrosurgical unit safety provided. PMID- 1929346 TI - Administrators should evaluate problems, not place blame. PMID- 1929347 TI - The deontological decision-making model as a bioethical tool. AB - Ethical decisions are difficult to handle and truly challenge everyone involved in the process. Nurses must appreciate the difficulty encountered when dealing with ethical decisions and begin their own investigations of other available decision-making models to choose one that best fits their own ethical beliefs and values. PMID- 1929348 TI - Lobbying and what nurses can do to promote legislation. PMID- 1929349 TI - Giant cerebral aneurysm repair. Incorporating cardiopulmonary bypass and neurosurgery. AB - Since our initial experience on April 28, 1989, a total of nine patients have received treatment for giant cerebral aneurysm using cardiopulmonary bypass with deep hypothermia and circulatory arrest. The following data summarize our findings associated with these patients. The average patient's age was 46 years (range: 16 to 59 years of age). Seven patients were female, two were male. The procedure required approximately eight hours to complete with an average cardiopulmonary bypass time of 104 minutes (range: 60 to 140 minutes). Circulatory arrest time averaged 26 minutes (range, 12 to 45 minutes) with an average of 30 minutes (range: 10 to 62 minutes) required to cool the patient to below 18 degrees C (64 degrees F). An average of 54 minutes (range: 28 to 81 minutes) was required to warm the patient to a bladder temperature of 36 degrees C (96.8 degrees F). During the cooling period, five patients went into asystole spontaneously, four patients required bolus of 20 mEq of potassium chloride, and upon rewarming, spontaneous defibrillation occurred in six patients. Three patients were defibrillated without difficulty with external shock. The average number of blood products administered in each of the nine patients was 3.6 units of packed red blood cells, 3 units of fresh frozen plasma, and 6.5 units of platelets. Six patients recovered postoperatively without complication, and the recovery of three patients was affected by the complex anatomical location of the giant aneurysm. Cardiopulmonary bypass with deep hypothermia and circulatory arrest offers an alternative approach to the treatment of giant cerebral aneurysms considered inoperable by conventional techniques. The effectiveness of each procedure depends on the collaborative efforts of every member of the perioperative nursing team, the neurosurgical team, the cardiac surgical team, the neuroanesthesiology team, and the perfusionists. Careful planning and anticipation at every stage of the surgery can reduce surgical time, cardiopulmonary bypass time, and most importantly, circulatory arrest time. PMID- 1929350 TI - Laser ablation of coronary arteries. Preliminary findings. PMID- 1929351 TI - Endometrial ablation with rollerball electrode. An alternative to hysterectomy. PMID- 1929352 TI - Bone cyst of the acetabulum. A case study. PMID- 1929353 TI - Emotional responses to infertility. Understanding patients' needs. PMID- 1929354 TI - Professional recognition. A manager's responsibility. PMID- 1929355 TI - Proposed recommended practices. Care of instruments, scopes, and powered surgical instruments. AORN Recommended Practices Coordinating Committee. PMID- 1929356 TI - Proposed recommended practices. Protective barrier materials for surgical gowns and drapes. AORN Recommended Practices Coordinating Committee. PMID- 1929357 TI - Emotional distress as a basis for claims. PMID- 1929358 TI - Implementing bar code technology in the OR. AB - A bar code system reduces the amount of time that nurses spend manually documenting patient care and performing other clerical tasks. By implementing a bar code system, nurses can spend more time giving patient care, risk managers can have more legible and complete documentation, and managers have access to a wide variety of useful reports. PMID- 1929359 TI - Aseptic technique adherence never goes out of style. PMID- 1929361 TI - Kinetic investigation and mathematical modeling of methanogenesis of glucose. AB - The kinetic regularities of anaerobic conversion of glucose, and intermediates of its decomposition (ethanol, butyrate, and acetate) by a microbial methanogenic association from anaerobic digester were investigated. Kinetic scheme for conversion of glucose is suggested, and the mathematical model based on the scheme is evolved. The model includes growth and metabolism of three kinds of microorganisms--acid producents, and acetate- and hydrogen-utilizing methane producents; of cell lysis with consequent fermentation of "died biomass" to acetate, hydrogen, and carbon dioxide; of induction and repression of the enzyme responsible for decomposition of butyrate, and for a number of regulations depending on the concentrations of intermediates in glucose metabolism. The values of parameters of the model have been calculated, sufficiently describing the experimental regularities. The numerical experiments have enabled us to reveal and describe the principal regulating factors of glucose methanogenesis. PMID- 1929360 TI - Ethanolic fermentation of pentoses in lignocellulose hydrolysates. AB - In the fermentation of lignocellulose hydrolysates to ethanol, two major problems are encountered: the fermentation of the pentose sugar xylose, and the presence of microbial inhibitors. Xylose can be directly fermented with yeasts, such as Pachysolen tannophilus, Candida shehatae, and Pichia stipis, or by isomerization of xylose to xylulose with the enzyme glucose (xylose) isomerase (XI; EC 5.3.1.5), and subsequent fermentation with bakers' yeast, Saccharomyces cerevisiae. The direct fermentation requires low, carefully controlled oxygenation, as well as the removal of inhibitors. Also, the xylose-fermenting yeasts have a limited ethanol tolerance. The combined isomerization and fermentation with XI and S. cerevisiae gives yields and productivities comparable to those obtained in hexose fermentations without oxygenation and removal of inhibitors. However, the enzyme is not very stable in a lignocellulose hydrolysate, and S. cerevisiae has a poorly developed pentose phosphate shunt. Different strategies involving strain adaptation, and protein and genetic engineering adopted to overcome these different obstacles, are discussed. PMID- 1929362 TI - Induction of mutation in Trichoderma viride for conversion of natural cellulose into glucose. PMID- 1929363 TI - Induction of mutation in Aspergillus niger for conversion of cellulose into glucose. PMID- 1929364 TI - Ethanol production by recombinant Escherichia coli carrying genes from Zymomonas mobilis. AB - Efficient utilization of lignocellulosic feedstocks offers an opportunity to reduce the cost of producing fuel ethanol. The fermentation performance characteristics of recombinant Escherichia coli ATCC 11303 carrying the "PET plasmid" (pLOI297) with the lac operon controlling the expression of pyruvate decarboxylase (pdc) and alcohol dehydrogenase II (adhB) genes cloned from Zymomonas mobilis CP4 (Alterthum & Ingram, 1989) were assessed in batch and continuous processes with sugar mixtures designed to mimic process streams from lignocellulosic hydrolysis systems. Growth was pseudoexponential at a rate (generation time) of 1.28 h at pH 6.8 and 1.61 h at pH 6.0. The molar growth yields for glucose and xylose were 17.28 and 7.65 g DW cell/mol, respectively (at pH 6.3 and 30 degrees C), suggesting that the net yield of ATP from xylose metabolism is only 50% compared to glucose. In pH-stat batch fermentations (Luria broth with 6% sugar, pH 6.3), glucose was converted to ethanol 4-6 times faster than xylose, but the glucose conversion rate was much less than can be achieved with comparable cell densities of Zymomonas. Sugar-to-ethanol conversion efficiencies in nutrient-rich, complex LB medium were near theoretical at 98 and 88% for glucose and xylose, respectively. The yield was 10-20% less in a defined mineral-salts medium. Acetate at a concentration of 0.1M (present in lignocellulosic hydrolysates from thermochemical processing) inhibited glucose utilization (about 50%) much more than xylose, and caused a decrease in product yield of about 30% for both sugars. With phosphate-buffered media (pH 7), glucose was a preferred substrate in mixtures with a ratio of hexose to pentose of 2.3 to 1. Xylose was consumed after glucose, and the product yield was less (0.37 g/g). Under steady-state conditions of continuous culture, the specific productivity ranged from 0.76-1.24 g EtOH/g cell/h, and the maximum volumetric productivity, 2.5 g EtOH/L/h, was achieved with a rich complex LB medium (glucose) at pH 6.0 (30 degrees C) and ethanol at 1.63% (v/v). Growth and fermentation were poor in a buffered-wood (aspen) "hemicellulose hydrolysate" containing 4% xylose and 0.1M acetate with added thiamine and mineral salts. PMID- 1929365 TI - Degradation of organic sulfur compounds by a coal-solubilizing fungus. AB - Paecilomyces sp. TLi, a coal-solubilizing fungus, was shown to degrade organic sulfur-containing coal substructure compounds. Dibenzothiophene was degraded via a sulfur-oxidizing pathway to 2,2'-dihydroxybiphenyl. No further metabolism of that compound was observed. Ethyl phenyl sulfide and diphenyl sulfide were degraded to the corresponding sulfones. A variety of products were formed from dibenzyl sulfide, presumably via free radical intermediates. Diphenyl disulfide and dibenzyl disulfide were cleaved to the corresponding thiols and other single ring products. It was concluded that degradation of organic sulfur compounds by Paecilomyces involves an oxidative attack localized at the sulfur atom. PMID- 1929366 TI - Growth kinetics of Bacillus stearothermophilus BR219. AB - Bacillus stearothermophilus BR219, a phenol-resistant thermophile, can convert phenol to the specialty chemical catechol. The growth kinetics of this organism were studied in batch, continuous, and immobilized-cell culture. Batch growth was insensitive to pH between 6.0 and 8.0, but little growth occurred at 5.5. In continuous culture on a dilute medium supplemented with 10 mM phenol, several steady states were achieved between dilution rates of 0.25 and 1.3 h-1. Phenol degradation was found to be uncoupled from growth. Immobilized cells grew rapidly in a rich medium, but cell viability plummeted following a switch to a dilute medium supplemented with 5 mM phenol. PMID- 1929367 TI - Degradation of furfural (2-furaldehyde) to methane and carbon dioxide by an anaerobic consortium. AB - Furfural, a byproduct formed during the thermal/chemical pretreatment of hemicellulosic biomass, was degraded to methane and carbon dioxide under anaerobic conditions. The consortium of anaerobic microbes responsible for the degradation was enriched using small continuously stirred tank reactor (CSTR) systems with daily batch feeding of biomass pretreatment liquor and continuous addition of furfural. Although the continuous infusion of furfural was initially inhibitory to the anaerobic CSTR system, adaptation of the consortium occurred rapidly with high rates of furfural addition. Addition rates of 7.35 mg furfural/700-mL reactor/d resulted in biogas productions of 375%, of that produced in control CSTR systems, fed the biomass pretreatment liquor only. The anaerobic CSTR system fed high levels of furfural was stable, with a sludge pH of 7.1 and methane gas composition of 69%, compared to the control CSTR, which had a pH of 7.2 and 77% methane. CSTR systems in which furfural was continuously added resulted in 80% of the theoretically expected biogas. Intermediates in the anaerobic biodegradation of furfural were determined by spike additions in serum bottle assays using the enriched consortium from the CSTR systems. Furfural was converted to several intermediates, including furfuryl alcohol, furoic acid, and acetic acid, before final conversion to methane and carbon dioxide. PMID- 1929368 TI - Toxic effects of selected industrial solvents in batch and continuous anaerobic reactors. AB - Acetone and ethyl acetate were readily degraded in batch reactors containing anaerobic solids from an industrial reactor at concentrations to 1000 mg/L; isoamyl acetate was degraded at concentrations below 200 mg/L. Xylene was noninhibitory in batch cultures at concentrations of 50 mg/L or less. Batch reactors receiving 45 mg/L methylene chloride (MC) experienced a 60% reduction in gas production, and an increase in volatile fatty acids. Semicontinuously-fed reactors dosed with 20 mg/L MC at the start suffered some loss of anaerobic efficiency, but acclimated well with increased gas production after 20 d. A continuously fed sludge blanket reactor with no previous exposure to MC has acclimated to 20 mg/L MC after initial inhibition at 10 mg/L. PMID- 1929369 TI - Selection of thermotolerant yeasts for simultaneous saccharification and fermentation (SSF) of cellulose to ethanol. AB - A total of 27 yeast strains belonging to the groups Candida, Saccharomyces, and Kluyveromyces were screened for their ability to grow and ferment glucose at temperatures ranging 32-45 degrees C. K. marxianus and K. fragilis were found to be the best ethanol producing organisms at the higher temperature tested and, so, were selected for subsequent simultaneous saccharification and fermentation (SSF) studies. SSF experiments were performed at 42 and 45 degrees C, utilizing Solkafloc (10%) as cellulose substrate and a cellulase loading of 15 FPU/g substrate. Best results were achieved at 42 degrees C with K. marxianus L. G. and K. fragilis L. G., both of which produced close to 38 g/L ethanol and 0.5 ethanol yield, in 78 h. PMID- 1929371 TI - Avoiding digester imbalance through real-time expert system control of dilution rate. AB - Process control of anaerobic digesters is a particularly challenging problem because of the diversity of possible causes that can lead to digester imbalance. Conventional control schemes can fail in consequence of a reversal in the sign of the steady-state gain caused by some type of disturbance. In this work we present an expert system approach that takes into account the particularity of this process. The developed algorithm is demonstrated to compensate successfully for changes in the digester feed medium when simulated against a model for a continuous anaerobic digester. PMID- 1929370 TI - Isolation of xylose reductase gene of Pichia stipitis and its expression in Saccharomyces cerevisiae. AB - A NADPH/NADH-dependent xylose reductase gene was isolated from the xylose assimilating yeast, Pichia stipitis. DNA sequence analysis showed that the gene consists of 951 bp. The gene introduced in Saccharomyces cerevisiae was transcribed to mRNA, and a considerable amount of enzyme activity was observed constitutively, whereas transcription and translation in P stipitis were inducible. S. cerevisiae carrying the xylose reductase gene could not, however, grow on xylose medium, and could not produce ethanol from xylose. Since xylose uptake and accumulation of xylitol by S. cerevisiae were observed, the conversion of xylitol to xylulose seemed to be limited. PMID- 1929372 TI - Nature of plant stimulators in the production of Acetobacter xylinum ("tea fungus") biofilm used in skin therapy. AB - Caffeine and related xanthines were identified as potent stimulators for the bacterial cellulose production in A. xylinum. These compounds are present in several plants whose infusions are useful as culture-medium supplements for this acetobacterium. The proposed target for these native purine-like inhibitory substances is the novel diguanyl nucleotide phosphodiesterase(s) that participate(s) in the bacterial cellulogenic complex. A better understanding of this feature of A. xylinum physiology may facilitate the preparation of bacterial cellulose pellicles, which are applied as a biotechnological tool in the treatment of skin burns and other dermal injuries. PMID- 1929373 TI - Cellulase production from spent sulfite liquor and paper-mill waste fiber. Scientific note. PMID- 1929374 TI - Genetic transformation of xylose-fermenting yeast Pichia stipitis. Scientific note. AB - A plasmid-mediated transformation system has been developed for the xylose fermenting yeast Pichia stipitis. We found that plasmid vectors containing the Saccharomyces cerevisiae 2 mu replicon and the kanamycin resistance gene (KmR) could be introduced into the Pichia cells and maintained as extrachromosomal elements. Pichia transformants containing such vectors will be resistant to the antibiotic geneticin that can be inactivated by the protein product of KmR. Plasmids identical to those used for transformation can be recovered from the Pichia transformants. Protocols for transformation of P. stipitis by the CaCl2 polyethylene glycol-protoplast process or by direct electroporation of intact Pichia cells have both been developed. PMID- 1929375 TI - Synthesis and properties of lignin peroxidase from Streptomyces viridosporus T7A. AB - The production of lignin peroxidase by Streptomyces viridosporus T7A was studied in shake flasks and under aerobic conditions in a 7.5-L batch fermentor. Lignin peroxidase synthesis was found to be strongly affected by catabolite repression. Lignin peroxidase was a non-growth-associated, secondary metabolite. The maximum lignin peroxidase activity was 0.064 U/mL at 36 h. In order to maximize lignin peroxidase activity, optimal conditions were determined. The optimal incubation temperature, pH, and substrate (2,4-dichlorophenol) concentration for the enzyme assays were 45 degrees C, 6, and 3 mM, respectively. Stability of lignin peroxidase was determined at 37, 45, and 60 degrees C, and over the pH range 4-9. PMID- 1929376 TI - A novel process for anaerobic composting of municipal solid waste. AB - A novel process has been developed and evaluated in a pilot-scale program for conversion of the biodegradable fraction of municipal solid waste (MSW) to methane via anaerobic composting. The sequential batch anaerobic composting (SEBAC) process employs leachate management to provide organisms, moisture, and nutrients required for rapid conversion of MSW and removal of inhibitory fermentation products during start-up. The biodegradable organic materials are converted to methane and carbon dioxide in 21-42 d, rather than the years required in landfills. PMID- 1929377 TI - Bioconversion of a L-carnitin precursor in a one- or two-phase system. AB - The ability of the yeast Saccharomyces cerevisiae to bioconvert stereo selectively octyl-4-chloroacetoacetate (OCA) into the corresponding chiral alcohol, precursor of L-carnitin, an important physiological agent, was investigated. In a monophasic system with free cells, more than 90% of OCA (0.018 M) bioconversion have been reached after 6 h (enantiomeric excess for the R form, eeR:97%). Immobilized cells in alginate beads were less efficient in conversion of OCA than free cells. In a two-phase system with free cells, the level of reduction of OCA (0.018 M) reached 85% after 48 h. With a medium containing a higher OCA concentration (0.270 M), 41% of this product were bioconverted after the same period. On the other hand, immobilized cells did not show any significant bioconversion of OCA in two-phase reactors. The limiting factor of these reactors in the regeneration of the cofactors involved in the OCA reduction. PMID- 1929378 TI - Performance of trickle-bed bioreactors for converting synthesis gas to methane. AB - Carbon monoxide, H2, and CO2 in synthesis gas can be converted to CH4 by employing a triculture of Rhodospirillum rubrum, Methanosarcina barkeri, and Methanobacterium formicicum. Trickle-bed reactors have been found to be effective for this conversion because of their high mass-transfer coefficients. This paper compares results obtained for the conversion of synthesis gas to CH4 in 5-cm- and 16.5-cm-diameter trickle-bed reactors. Mass-transfer and scale-up parameters are defined, and light requirements for R. rubrum are considered in bioreactor design. PMID- 1929379 TI - Growth of aerobic bacteria on alkali-solubilized lignite. Scientific note. PMID- 1929380 TI - Development of a differential volume reactor system for soil biodegradation studies. AB - A bench scale experimental system was developed for the analysis of polycyclic aromatic hydrocarbon (PAH) degradation by mixed microbial cultures in PAH contaminated Manufactured Gas Plant (MGP) soils and on sand. The reactor system was chosen in order to provide a fundamental protocol capable for evaluating the performance of specific mixed microbial cultures on specific soil systems by elucidating the important system variables and their interactions. The reactor design and peripherals are described. A plug flow differential volume reactor (DVR) was used in order to remove performance effects related to reactor type, as opposed to system structure. This reactor system could be well represented mathematically. Methods were developed for on-line quantitative determination of PAH liquid phase concentrations. The mathematical models and experimental data are presented for the biodegradation of naphthalene on artificial and MGP soils. PMID- 1929381 TI - Simultaneous combined microbial removal of sulfur dioxide and nitric oxide from a gas stream. AB - A program is under way at the University of Tulsa to develop a viable process concept whereby a microbial process can impact on the problem of flue gas desulfurization and NOx removal. We have previously reported studies of SO2 reduction by Desulfovibrio desulfuricans and NOx reduction by Thiobacillus denitrificans. One potential process concept is the simultaneous combined removal of SO2 and NOx from cooled flue gas by contact with cultures of sulfate-reducing bacteria (SO2----H2S) and T. denitrificans (H2S----SO4(-2) as cultures-in-series or in coculture in a single contacting stage. Each of these contacting schemes has been investigated. PMID- 1929382 TI - An economic analysis of microbial reduction of sulfur dioxide as a means of byproduct recovery from regenerable processes for flue gas desulfurization. PMID- 1929383 TI - A structured model for vegetative growth and sporulation in Bacillus thuringiensis. AB - A mathematical model has been developed for the delta-endotoxin producing Bacillus thuringiensis. The structure of the model involves the processes taking place during vegetative growth, those leading to the initiation of sporulation under conditions of carbon and/or nitrogen limitation, and the sporulation events. The key features in the model are the pools of compounds, such as PRPP, IMP, ADP/ATP, GDP/GTP, pyrimidine nucleotides, NAD/NADH2, amino acids, nucleic acids, cell wall, and vegetative and sporulation proteins. These, along with sigma-factors that control the nature of RNA-polymerase during the different phases, effectively stimulate the vegetative growth and sporulation. The initiation of sporulation is controlled by the intracellular concentration of GTP. Results of simulation of vegetative growth, initiation of sporulation, spore protein formation, and production of delta-endotoxin under C- or N-limitation are presented. PMID- 1929384 TI - COS degradation by selected CO-utilizing bacteria. Scientific note. PMID- 1929385 TI - Respirometric analysis of the biodegradation of organic contaminants in soil and water. AB - Client-funded bench-scale investigations concerning the likelihood of successfully applying biological remediation to hazardous wastes must be cost effective, and they usually need only determine if biodegradation is likely to occur on site. To assess the potential for stimulating biodegradation, biochemical oxygen demand (BOD) was used to continuously monitor bacterial respiration during growth on mixed organic wastes from contaminated water and soil. Continuously collected oxygen-consumption data provided information on the overall metabolic activity of the resident bacterial population and permitted direct observation of the cessation of microbial respiratory activity and, thus, the termination of aerobic degradation. The correlation of biological oxygen utilization with biodegradation was confirmed using independent analytical methods. Continuous, long-term BOD analysis was applied to bench-scale studies to assess the biodegradation of mixed organic wastes from contaminated sites and industrial waste effluents. This information was used to make an initial determination regarding the need to further explore bioremediation as a potential remedial-action technology using on-site, pilot-scale testing. PMID- 1929386 TI - Novel biotreatment process for glycol waters. AB - Propylene oxide (PO), propylene glycol (PG), and polyols are produced from propylene via propylene chlorohydrin. Effluents from these plants contain biological oxygen demand/chemical oxygen demand (BOD/COD) loads besides high chloride concentrations. The high salinity poses severe problem to adopt conventional methods like activated sludge processes. Presently, a simple, economically viable and versatile microbiological process has been developed to get more than 90% biodegradation in terms of BOD/COD, utilizing specially developed Pseudomonas and Aerobacter. The process can tolerate high salinity up to 10 wt% NaCl or 5 wt% CaCl2 and can withstand wide variations in pH (5.5-11.0) and temperature (15-45 degrees C). The biodegradation of glycols involves two steps. The enzymatic conversion of glycols to carboxylic and hydroxycarboxylic acids is aided by Pseudomonas. Further degradation to CO2 and H2O by carboxylic acid utilizing Aerobacter, and possible metabolic degradative pathway of glycols are discussed. Various process parameters obtained in the lab scale (50 L bioreactor) and pilot scale (20 m3 bioreactor), and unique features of our process are also discussed. PMID- 1929387 TI - Study of BOD microbial sensors for waste water treatment control. AB - A microbial sensor consisting of immobilized yeast or bacterial cells and an oxygen electrode was developed for the estimation of biochemical oxygen demand (BOD). A flow-through system was used, and the response time was within 20 min. A linear relationship was observed between the relative current decrease and the BOD of the sample solution within the range of 1-45 mg/L. The storage lifetime was greater than 1 yr. The reproducibility was quite good, within 6% fsd at a concentration of 20 mg/L BOD. Satisfactory results were attained when the biosensor was applied to the determination of BOD in brewery-plant and glutamate plant wastewater and in a river. PMID- 1929388 TI - Degradation of organic cyanides by Pseudomonas aeruginosa. AB - A bacterium capable of utilizing acetonitrile (methyl cyanide) as the sole source of carbon and nitrogen was isolated from soil and identified as Pseudomonas aeruginosa. This bacterium could also utilize and oxidize numerous lower-mol-wt nitrile compounds and their corresponding amides as growth substrates. A metabolite of acetonitrile in the culture medium was determined to be ammonia. The accumulation of ammonia in the culture medium was proportional to the concentration of the substrate and the inoculum. Cell extracts of the bacterium contained activities corresponding to nitrile aminohydrolase (E C 3.5.5.1) and amidase (E C 3.5.1.4), which regulate the degradation of acetonitrile. Both enzymes were inducible and hydrolyzed a wide range of substrates, and it was determined that the specific activity of amidase was far greater than the activity of nitrile aminohydrolase. PMID- 1929389 TI - Growth of microalgae in high CO2 gas and effects of SOX and NOX. AB - Growth and lipid production of microalgae were investigated, with attention to the feasibility of making use of flue gas CO2 as a carbon source. The effect of a high CO2 level in artificial seawater differed from strain to strain. Three algal strains from the Solar Energy Research Institute (Golden, CO) collection were selected as good fixers of CO2 when the level of CO2 in the sparging gas was high. These algae also accumulated large amounts of crude lipids. SOx and NOx inhibited algal growth, but a green alga, Nannochloris sp. NANNO2 grew after a lag period, even when it received NO gas at the concentration of 300 ppm. PMID- 1929391 TI - Bench scale studies of the soil aeration process for bioremediation of petroleum hydrocarbons. AB - An alternative to traditional hydrocarbon bioremediation is to pump air through unsaturated soils to create aerobic conditions and induce biodegradation. This study examines the effects of moisture and nutrient augmentation on biodegradation of petroleum hydrocarbons in aerated soils. Findings indicate that forced aeration, coupled with additions of nutrients and moisture, stimulate hydrocarbon-degrading microorganisms and present a feasible approach to bioremediation management. PMID- 1929390 TI - Methanol suppression of trichloroethylene degradation by Methylosinus trichosporium (OB3b) and methane-oxidizing mixed cultures. AB - The effect of methanol on trichloroethylene (TCE) degradation by mixed and pure methylotrophic cultures was examined in batch culture experiments. Methanol was found to relieve growth inhibition of Methylosinus trichosporium (OB3b) at high (14 mg/L) TCE concentrations. Degradation of TCE was determined by both radiolabeling and gas chromatography techniques. When cultures were grown on methanol over 10 to 14 d with 0.3 mg/L TCE, OB3b degraded 16.89 +/- 0.82% (mean +/- SD) of the TCE, and a mixed culture (DT type II) degraded 4.55 +/- 0.11%. Mixed culture (JS type I) degraded 4.34 +/- 0.06% of the TCE. When grown on methane with 0.3 mg/L TCE, 32.93 +/- 2.01% of the TCE was degraded by OB3b, whereas the JS culture degraded 24.3 +/- 1.38% of the TCE, and the DT culture degraded 34.3 +/- 2.97% of the TCE. The addition of methanol to cultures grown on methane reduced TCE degradation to 16.21 +/- 1.17% for OB3b and to 5.08 +/- 0.56% for JS. Although methanol reduces the toxicity of TCE to the cultures, biodegradation of TCE cannot be sustained in methanol-grown cultures. Since high TCE concentrations appear to inhibit methane uptake and growth, we suggest the primary toxicity of TCE is directed towards the methane monooxygenase. PMID- 1929392 TI - Iron oxidation by Thiobacillus ferrooxidans. Scientific note. PMID- 1929393 TI - Free-living amoebae used to isolate consortia capable of degrading trichloroethylene. Scientific note. PMID- 1929394 TI - Effect of pretreatment on simultaneous saccharification and fermentation of hardwood into acetone/butanol. AB - The effectiveness of pretreatments on hardwood substrate was investigated in connection with its subsequent conversion by simultaneous saccharification and fermentation (SSF), using Clostridium acetobutylicum. The main objectives of the pretreatment were to achieve efficient separation of lignin from carbohydrates, and to obtain maximum sugar yield on enzymatic hydrolysis of pretreated wood. Two methods have given promising results: (1) supercritical CO2-SO2 treatment, and (2) monoethanolamine (MEA) treatment. The MEA pretreatment removed above 90% of hardwood lignin while retaining 83% of carbohydrates. With CO2-SO2 pretreatment, the degree of lignin separation was lower. Under the scheme of SSF, the pretreated hardwood was converted to acetone, butanol, and ethanol (ABE) via single stage processing by cellulase enzyme system and C. acetobutylicum cells. The product yield in the process was such that 15 g of ABE/100 g of dry aspen wood was produced. In the overall process of SSF, the enzymatic hydrolysis was found to be the rate-limiting step. The ability of C. acetobutylicum to metabolize various 6-carbon and 5-carbon sugars resulted in efficient utilization of all available sugars from hardwood. PMID- 1929395 TI - Purification and characterization of a trypsin inhibitor from mouse seminal vesicle secretion. AB - A Kazal-type trypsin inhibitor in mouse seminal vesicle secretion was purified to homogeneity via a series of purification steps including ammonium sulfate fractionation, affinity chromatography on a trypsin Affi-Gel 10 column, and HPLC on a reverse phase C4 column. It was shown to be a weak basic protein with an isoelectric point of 8.7 and to contain no carbohydrate. The protein had a specific activity of 184 U/mg protein in the inhibitory effect on the trypsin digestion of N-benzoyl-Pro-Phe-Arg-p-nitroanilide. Analysis of the kinetic data for the trypsin digestion of N-benzoyl-Phe-Val-Arg 7-amido-4-methylcoumarin revealed that the protein was a competitive inhibitor with an inhibitory constant (Ki) of 0.15 nM. The molecular mass of the protein was determined to be 7 kDa by both gel chromatography and electrophoresis. Results of direct amino acid determinations indicated that this protein corresponded to the reading frame of MP12 cDNA identified from mouse prostate. We found that cleavage only at the reactive site of this protein (Arg19-Ile20) resulted in its denaturation. PMID- 1929396 TI - NADP(+)-malic enzyme from sugarcane leaves: structural properties studied by thermal inactivation. AB - The irreversible thermal inactivation of the sugarcane leaf NADP(+)-malic enzyme was studied at 50 degrees C and pH 7.0 and 8.0. Depending on the preincubation conditions, thermal inactivation followed mono- or biphasic first-order kinetics. A two-step behavior in the irreversible denaturation process was found when protein concentration was sufficiently low. The protein concentration necessary to obtain monlphasic thermal inactivation kinetics was lower at pH 8.0 than at pH 7.0. The results suggest that biphasic inactivation kinetics are the consequence of the existence of two different oligomeric forms of the enzyme (dimer and tetramer), with the dimer being more stable in regards to thermal inactivation. The effects of the substrate and essential cofactors on the thermostability and equilibrium between the dimeric and tetrameric enzyme forms were also studied. Depending on the pH, NADP+, L-malate, and Mg2+ all had a protective effect on the stability of the dimeric and tetrameric species during thermal treatment. However, these ligands showed different effects on the aggregation state of the enzyme. NADP+ and L-malate induced dissociation, especially at pH 8.0, whereas Mg2+ induced aggregation of the protein. By studying the thermal inactivation kinetics at 50 degrees C and different pH values it was observed that the equilibrium between dimers and tetramers was dramatically affected in the range of pH 7.0-8.0. These results suggest that an amino acid residue(s) in the protein with an apparent pKa value of 7.7 needs to be deprotonated to stabilize aggregation of the enzyme to the tetrameric form. PMID- 1929397 TI - Identification and characterization of an NADPH-cytochrome P450 reductase derived peptide involved in binding to cytochrome P450. AB - The amino acids of cytochrome P450 reductase involved in the interaction with cytochrome P450 were identified with a differential labeling technique. The water soluble carbodiimide EDC (1-ethyl-3-[3- (dimethylamino)propyl]-carbodiimide) was used with the nucleophile methylamine to modify carboxyl residues. When the modification was performed in the presence of cytochrome P450, there was no inhibition in the ability of the modified reductase to bind to cytochrome P450. However, subsequent modification of the reductase in the absence of cytochrome P450 caused a fourfold increase in the Km and an 80% decrease in kcat/Km (relative to the reductase modified in the first step), for the interaction with cytochrome P450. These effects are attributed to the modification of approximately 3.2 mol of carboxyl residues per mole of reductase. Tryptic peptides generated from the modified reductase were purified by reverse phase high-performance liquid chromatography and characterized. Amino acid sequencing and analysis suggest that the peptide which contains approximately 40% of the labeled carboxyl residues corresponds to amino acid residues 109-130 of rat liver NADPH-cytochrome P450 reductase. One or more of the seven carboxyl containing amino acids within this peptide is presumably involved in the interaction with cytochrome P450. PMID- 1929398 TI - Purification of human cytidine deaminase: molecular and enzymatic characterization and inhibition by synthetic pyrimidine analogs. AB - Cytidine deaminase has been purified to homogeneity from human placenta by a rapid and efficient procedure consisting of affinity chromatography followed by hydrophobic interaction chromatography. The final enzyme preparation showed a specific activity of 64.1 units/mg, corresponding to about 46,000-fold purification with respect to the crude extract. The enzyme is a 52-kDa oligomeric protein composed of four apparently identical subunits. The acidic isoelectric point is 4.5. The enzyme's stability is strictly dependent on the presence of reducing agents. Amino acid analysis reveals the presence of five thiol groups per monomer which cannot be titrated by Ellman's reagent in the native enzyme. However, the presence of sulfhydryl groups involved in the catalytic activity was evidenced by the inhibition exerted by p-chloromercuribenzoate and heavy metal ions. In addition, the protection effected by the substrate against the p chloromercuribenzoate inhibition and the competitive inhibition exerted by 5 (chloromercuri)cytidine suggest the presence of a thiol group(s) in the catalytic site of the enzyme. pH studies have shown that the rapid decline of activity occurring at pH 4.5 might result from the protonation of the pyrimidine ring at the N-3 position. The enzyme catalyzes the deamination of cytidine, deoxycytidine, and several analogs, including antineoplastic agents, thus abolishing their pharmacological activity. Therefore, several pyrimidine nucleoside analogs have been tested as potential inhibitors of the enzyme. The competitive inhibition exerted by cytidine analogs having the ribose moiety replaced by aliphatic chains is interesting. PMID- 1929399 TI - Purification and characterization of two ribonucleases from developing tomato fruit. AB - Two neutral ribonucleases have been purified from developing tomato fruit. Their activity is maximal 5 days after anthesis, declines during maturation, and then increases slightly in the mature green through breaker stages. The ribonucleases Tf1 and Tf2 have molecular weights of 59 and 29 K, respectively, based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and are glycoproteins. The reduced and denatured Tf1 is composed of two subunits, 30 and 29 K, of which only the 30-K subunit displays ribonuclease activity after renaturation. Reduced and denatured Tf2 is a single 29-K polypeptide that is renaturable to an active ribonuclease. Only the 30-K, active subunit of Tf1 is immunologically cross reactive with Tf2. Both ribonucleases are cyclyzing endoribonucleases with a strong preference for cleavage at pyrimidine residues, thus generating oligonucleotide products ending with pyrimidine 2',3'-cyclic phosphate. These tomato fruit ribonucleases share a number of properties in common with the S glycoprotein ribonucleases that are involved in self-incompatibility reactions in some solanaceous plants. PMID- 1929400 TI - Deantigenation of human erythrocytes by bacterial glycosidases--evidence for the noninvolvement of medium-sized glycosphingolipids in the Dolichos biflorus lectin hemagglutination. AB - Fresh human A1 erythrocytes, washed and pretreated in phosphate buffer with or without papain, were incubated at 37 degrees C with blood group-degrading enzymes from the human fecal Ruminococcus torques strain IX-70. The effects were assayed as changes in hemagglutination patterns, and blood group activities of alkali stable glycolipid extracts from the enzyme-treated cells using Dolichos biflorus anti-A1 lectin, Ulex europaeus type 1 anti-H lectin, and various monoclonal anti A antibodies. Hemolysis was negligible (less than or equal to 1% after 6 h), and the osmotic fragility increased slightly only after papain treatment. The papain untreated A1 erythrocytes lost D. biflorus agglutinability within minutes at room temperature with the unfractionated bacterial enzyme mixture IX-70 (42 mU 1,3 alpha-N-acetylgalactosaminidase (alpha-GalNAc'ase)/ml), but remained A active by strong agglutination with BioClone anti-A antibody even after 6 h of incubation. Thin layer chromatographic (TLC) immunostaining of extracted lipids showed hydrolysis of D. biflorus binding glycosphingolipids with more than six monosaccharides after 1 h, i.e., at a slower rate than the loss of D. biflorus agglutinability. Disappearance of these glycosphingolipids after 1 h paralleled the appearance of U. europaeus agglutinability and the strong binding of this lectin to glycolipid extracts in TLC immunoassays. A partly purified 1,3-alpha GalNAc'ase (XI-117) (100 mU/ml) and a 1,2-alpha-fucosidase fraction (XI-50) containing alpha-GalNAc'ase (10 mU/ml) did not degrade blood group A active glycosphingolipids but completely abolished the D. biflorus agglutinability within 6 h. Papain pretreatment exposed U. europaeus receptors on the cell surface without changing the A1 hemagglutination pattern. It also facilitated a complete degradation of D. biflorus and U. europaeus reactive glycolipids with the IX-70 enzyme mixture within 6 h. The D. biflorus lectin was a good discriminator of A1/A2 subjects using erythrocyte lipid extracts but had a low affinity for the blood group A type 3 and type 4 glycosphingolipids in the TLC overlay technique. In conclusion this study shows that (i) loss of D. biflorus A1 hemagglutination does not correlate with a loss of D. biflorus binding glycosphingolipids and (ii) loss of D. biflorus binding glycosphingolipids does not correlate with a loss of D. biflorus agglutinability. The results indicate that the serological D. biflorus agglutinability of A1 erythrocytes is not dependent on medium-sized glycosphingolipids (hexa- to dodecaglycosylceramides). PMID- 1929401 TI - Metabolism of 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(R)-HETE) in corneal tissues: formation of novel metabolites. AB - 12(R)-Hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE], a cytochrome P450 arachidonate metabolite, is metabolized by corneal tissues via three distinct metabolic pathways: beta-oxidation, omega-hydroxylation, and keto-reduction. The major metabolite released from the intact rabbit corneal epithelium or cultured cells was identified by mass spectrometric analysis as 8-hydroxy-4,6,10 hexadecatrienoic acid, the tetranor metabolite derived following two steps of beta-oxidation from the carboxy terminus. The beta-oxidation pathway was expressed in both microsomes and mitochondria isolated from bovine corneal epithelium and was dependent on the addition of oxidizing equivalents. The major metabolite of 12(R)-HETE in subcellular fractions of bovine corneal epithelial cells was a dihydro compound, 12-hydroxy-5,8,14-eicosatrienoic acid (12-HETrE). This derivative is presumably formed by an oxidation of the hydroxyl group followed by two keto-reduction steps, since its formation was accompanied by the appearance of a keto metabolite identified as 12-oxo-5,8,14-eicosatrienoic acid. The omega-hydroxylation, in contrast to other cell types, was a minor route for 12(R)-HETE metabolism in these tissues. Since 12(R)-HETE has been implicated as a modulator of Na(+)-K(+)-ATPase activity and its related functions in ocular tissues, these findings raise the possibility that the newly described metabolites may be involved in regulating corneal functions. In addition, the presence of a keto reductase in the cornea may be of great importance following injury since 12(R)-HETrE resulting from 12(R)-HETE by this activity is a potent ocular proinflammatory compound. PMID- 1929402 TI - Characterization of a cDNA-encoding rabbit brain heme oxygenase-2 and identification of a conserved domain among mammalian heme oxygenase isozymes: possible heme-binding site? AB - A 1.3-kb rat testis cDNA clone for heme oxygenase-2 (HO-2) was used as a Northern blot hybridization probe, and a single homologous mRNA species, of approximately 1.3 kb in rabbit brain and testis was detected. This contrasted with the observation made with rat brain in which two HO-2 transcripts of approximately 1.3 and 1.9 kb were detected. Use of the same rat HO-2 probe to screen a rabbit brain cDNA library in lambda gt11 resulted in the recovery of a single 1.2-kb cDNA clone. This cDNA exhibits 84% overall nucleotide sequence homology with rat HO-2 and encodes a protein of 35,352 Da, displaying 88% amino acid sequence homology with rat testis HO-2. Furthermore, when expressed in Escherichia coli, the rabbit cDNA-encoded protein displays heme oxygenase activity and cross reactivity with antibody to rat HO-2. Based on findings obtained through Western immunoblot analysis of partially purified HO-2 protein prepared from rabbit testis and brain, the 35- to 36-kDa molecular form appears to be the major HO-2 form detected in the brain, whereas a 42-kDa species is the predominant form observed in rabbit testis. Having deduced the amino acid sequence of rabbit brain HO-2, we provide a comparison of this sequence with those of rat, mouse, and human HO-1 and rat HO-2, and thereby identify a 24-amino-acid-long peptide region which, except for one residue, is identical in all five species of HO-1 and HO-2 compared (96% similarity), and exhibits 100% similarity in predicted secondary structure (for this region) in all five proteins. We propose that this peptide may be important to the heme binding and isomer-specific tetrapyrrole cleavage activities of the heme oxygenase isozymes. PMID- 1929403 TI - Biotransformation of lovastatin. IV. Identification of cytochrome P450 3A proteins as the major enzymes responsible for the oxidative metabolism of lovastatin in rat and human liver microsomes. AB - Previous studies from our laboratories have shown that the metabolism of the cholesterol-lowering drug lovastatin by rat and human liver microsomes occurs primarily at the 6'-position, giving 6' beta-hydroxy- and 6'-exomethylene lovastatin and that these oxidations are catalyzed by cytochrome P450-dependent monooxygenases. In the present study, the specific cytochrome P450 form involved in lovastatin oxidation was identified through immunoinhibition studies. Among several antibodies prepared against various cytochrome P450s, only anti-rat P450 3A IgG inhibited lovastatin metabolism in liver microsomes from untreated, phenobarbital-treated, and pregnenolone-16 alpha-carbonitrile-treated rats. Lovastatin metabolism at the 6'-position was markedly inhibited (6' beta-hydroxy, greater than 95%; 6'-exomethylene, 70-80%) by this antibody whereas the effect of anti-rat P450 3A on the 3"-hydroxylation was variable depending on the source of the microsomes. With human liver microsomes, both anti-rat P450 3A and anti-human P450 3A inhibited lovastatin metabolism. Correlation between lovastatin oxidation and the P450 3A content in human liver microsomes (measured by immunoblot analysis) was excellent (r2 = 0.97). In addition, preincubation of human liver microsomes with troleandomycin and NADPH inhibited metabolism by 60%. These results clearly indicate that cytochrome P450 3A enzymes are primarily responsible for the metabolism of lovastatin in rat and human liver microsomes. PMID- 1929404 TI - Purification and amino-terminal sequence of the bovine cardiac sodium-calcium exchanger: evidence for the presence of a signal sequence. AB - The Na(+)-Ca2+ exchange carrier was purified from bovine cardiac tissue by a new procedure which relies principally upon anion-exchange chromatography. The purified protein exhibited two major bands on sodium dodecyl sulfate gels, at 120 and 160 kDa. The relative intensities of the two bands could be altered by variations in the procedures used for preparing the samples for electrophoresis, suggesting that they represent two different conformational states of the same protein. The NH2-terminal amino acid sequences of the 120- and 160-kDa bands were identical and agreed closely with a region of the deduced amino acid sequence of the recently cloned canine cardiac exchanger. The NH2-terminal sequence was preceded in the deduced sequence by a 32-residue segment that exhibited the characteristics of a signal sequence; the initial amino acid in the NH2-terminal sequence followed immediately after the predicted cleavage site for the signal sequence. The Na(+)-Ca2+ exchanger appears to be unique among membrane transport carriers in encoding a cleaved signal sequence. The characteristics of the sequences flanking the first putative transmembrane segment of the mature exchanger suggest that the signal sequence is necessary to ensure the correct topological orientation of the exchanger in the membrane. PMID- 1929405 TI - Expression of functional bovine cholesterol side chain cleavage cytochrome P450 (P450scc) in Escherichia coli. AB - Escherichia coli expression vectors containing the trc promoter and the complete DNA sequence of either the precursor or the mature form of bovine adrenocortical cholesterol side chain cleavage cytochrome P450 (P450scc) were transformed into E. coli strain JM109 and transcription induced with isopropyl-beta-D thiogalactopyranoside (IPTG). Immunoreactive cytochrome P450scc was produced using the plasmid containing the mature P450scc sequence but not with the plasmid containing the sequence of the precursor form of P450scc, even though P450scc RNA was detectable in both cases. The mature form of P450scc was detected spectrophotometrically in a reduced CO-difference spectrum in E. coli (40-60 nmol/liter culture). Cholesterol and hydroxylated derivatives (22 hydroxycholesterol and 25-hydroxycholesterol) produce a type 1 substrate-binding spectrum in IPTG-induced, transformed E. coli. The P450scc was found to be associated with the E. coli membrane fraction and the enzymatic activity of side chain cleavage of 25-hydroxycholesterol was reconstituted using solubilized membranes, in the presence of purified bovine adrenocortical adrenodoxin and NADPH-adrenodoxin reductase (turnover number; 15.4 nmol/min/nmol P450). This bacterial expression system provides functional P450scc, in the absence of other forms of P450, which can be used for evaluation of enzymatic and spectral properties of this mitochondrial P450 by site-directed mutagenesis. PMID- 1929406 TI - Does helix dipole have any role in binding metal ions in protein structures? AB - Positions of metal-binding residues with respect to helical terminii in protein structures have been analyzed in order to determine if the location of these ligands is influenced by the helix dipole. Most ligands do not show any preference for the amino- or carboxy-terminus of a helix. For steric reasons, peptide ligands can be located only at the C-terminus. The availability of a second ligand residue closely placed along the sequence may be of more importance, rather than the electrostatic interaction involving helix dipole, in cases where ligands are found near the C-terminus. The location of heme-binding histidine residues at the C-terminus may be due to the steric requirements of the heme group and also the intrahelical hydrogen bond that the residues can form at this position. Considerations based on such geometrical features and not just the helix dipole may help us to understand the observed distribution of charged residues along alpha-helices and the favorable role these amino acids have on folding of isolated helices. PMID- 1929407 TI - Large disulfide-stabilized proteoglycan complexes are synthesized by the epidermis of axolotl embryos. AB - Proteoglycans (PGs) synthesized by the epidermis during stages crucial to the subepidermal migration of neural crest cells in the trunk of the axolotl (Ambystoma mexicanum, Urodela, Amphibia) embryo were studied. The glycosaminoglycan chains were biosynthetically labeled with [35S]sulfate in vitro during a period corresponding to the onset of migration. After extraction with guanidine HCl, the radiolabeled PGs were separated according to size by molecular sieve chromatography on Sepharose CL-2B under dissociative conditions. This resulted in the separation of high-molecular-weight PGs, which eluted in the void volume, and low-molecular-weight PGs, eluting in a broad peak with a mean Kav of 0.7. The large PGs were also found to elute in the void volume when chromatographed on a Sephacryl S-1000 column. The low-molecular-weight PGs contained heparan sulfate and chondroitin sulfate (CS) and were not further characterized. The glycosaminoglycan component of the high-molecular-weight PG was completely degraded by chondroitinase ABC, while a large portion was resistant to chondroitinase AC, indicating the presence of dermatan sulfate (DS). These CS/DS chains were of unusually large size (Mr approximately 150,000) as estimated by chromatography on Sepharose CL-4B, relating the elution position to hyaluronan standards. Moreover, the chains were found to have a lower surface charge density than standard CS, and may therefore be undersulfated. After reduction and alkylation the high-molecular-weight PGs were included on both Sepharose CL-2B and Sephacryl S-1000 columns, eluting at Kav 0.2 and 0.4, respectively. Hence, the high-molecular-weight material appears to consist of large PG complexes, stabilized by intermolecular disulfide bonds. A CS/DSPG of similar size as the reduced monomeric form of the high-molecular-weight PG was found in small amounts in the total extract of 35S-labeled material. PMID- 1929408 TI - Control of cytochromes P450 expression in Gunn rat liver: implication of the intracellular heme pool. AB - The absence of changes in the overall hepatic cytochrome P450 content after administration of 3-methylcholanthrene (MC) to congenitally jaundiced Gunn rats is believed to be related to a limited heme availability in this strain of rat. The amount of available heme, estimated by tryptophan pyrrolase activity, shows a substantial decrease in control Gunn versus control Wistar rats. This reduction is moderately enhanced by MC treatment in Gunn rats but is abolished after phenobarbital administration. Heme oxygenase activity is diminished in Gunn rats and consequently is not responsible for the decrease in the hepatic heme availability. These data point out that the depletion of the intracellular heme can lead to a limitation in the synthesis of cytochrome P450 isoenzymes in the MC induced Gunn rat. PMID- 1929409 TI - Purification and characterization of a GTP-binding protein serving as pertussis toxin substrate in starfish oocytes. AB - In response to a meiosis-inducing hormone, 1-methyladenine (1-MA), starfish oocytes undergo reinitiation of meiosis with germinal vesicle breakdown. The 1-MA initiated signal is, however, inhibited by prior microinjection of pertussis toxin into the oocytes (Shilling, F., Chiba, K., Hoshi, M., Kishimoto, T., and Jaffe, L.A. (1989) Dev. Biol. 133, 605-608), suggesting that a pertussis-toxin sensitive guanine-nucleotide-binding protein (G protein) is involved in the 1-MA induced signal transduction. Based on these findings, we purified a G protein serving as the substrate of pertussis toxin from the plasma membranes of starfish oocytes. The purified G protein had an alpha beta gamma-trimeric structure consisting of 39-kDa alpha, 37-kDa beta, and 8-kDa gamma subunits. The 39-kDa alpha subunit contained a site for ADP-ribosylation catalyzed by pertussis toxin. The alpha subunit was also recognized by antibodies specific for a common GTP binding site of many mammalian alpha subunits or a carboxy-terminal ADP ribosylation site of mammalian inhibitory G-alpha. An antibody raised against mammalian 36-/35-kDa beta subunits strongly reacted with the 37-kDa beta subunit of starfish G protein. The purified starfish G protein had a GTP-binding activity with a high affinity and displayed a low GTPase activity. The activity of the G protein serving as the substrate for pertussis-toxin-catalyzed ADP-ribosylation was inhibited by its association with a non-hydrolyzable GTP analogue. Thus, the starfish G protein appeared to be similar to mammalian G proteins at least in terms of its structure and properties of nucleotide binding and the pertussis toxin substrate. A possible role of the starfish G protein is also discussed in the signal transduction between 1-MA receptors and reinitiation of meiosis with germinal vesicle breakdown. PMID- 1929410 TI - Oxylipin metabolism in the red alga Gracilariopsis lemaneiformis: mechanism of formation of vicinal dihydroxy fatty acids. AB - Conversion of arachidonic acid into the vicinal diol fatty acid 12R,13S-dihydroxy 5Z,8Z,10E,14Z-eicosatetraenoic acid using an acetone powder of the marine red alga, Gracilariopsis lemaneiformis, occurred via intermediate formation of 12S hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid. Incubations of the linoleic acid derived 13S- and 13R-hydroperoxy-9Z,11E-octadecadienoic acids led to the formation of 13R,14S-dihydroxy-9Z,11E-octadecadienoic acid and 13S,14S-dihydroxy 9Z,11E-octadecadienoic acid, respectively, whereas incubation of 9S-hydroperoxy 10E,12Z-octadecadienoic acid resulted in the formation of 8S,9R-dihydroxy-10E,12Z octadecadienoic acid. Experiments with 18O2-labeled 13S hydroperoxyoctadecadienoic acid demonstrated that the oxygens of the two hydroxyl groups of 13R,14S-dihydroxy-9Z,11E-octadecadienoic acid originated in the hydroperoxy group of the substrate. Furthermore, experiments with mixtures of unlabeled and 18O2-labeled 13S-hydroperoxyoctadecadienoic acid showed that conversion into 13R,14S-dihydroxyoctadecadienoic acid occurred by a reaction involving an intramolecular hydroxylation at C-14 by the distal hydroperoxide oxygen. The existence of a hydroperoxide isomerase in G. lemaneiformis which catalyzes the conversion of fatty acid hydroperoxides into vicinal diol fatty acids is postulated. PMID- 1929411 TI - Mitochondrial phosphatidate is converted to triacylglycerol in rat hepatocytes. AB - Phosphatidate is formed in both the endoplasmic reticulum and the outer mitochondrial membrane in rat liver. To investigate whether the phosphatidate synthesized in mitochondria can be converted to triacylglycerol in vivo, two experimental approaches were employed. (i) [3H]Phosphatidate-labeled mitochondria were enclosed in plasma membrane vesicles and these fused, in the presence of inactivated Sendai virus and calcium ions, to hepatocytes in monolayer culture. The recovery of radioactivity in various cell-associated lipids was measured. (ii) Mitochondrial phosphatidate was labeled with [14C]palmitate in hepatocytes which had been permeabilized with lysophosphatidylcholine and in which the microsomal glycerolphosphate acyltransferase had been inhibited with N ethylmaleimide. The recovery of radioactivity in various lipids after incubation with particle free supernatant was measured. Evidence was obtained from both these experimental approaches that mitochondrial phosphatidate can be converted to triacylglycerol in rat hepatocytes. The results are discussed in relation to the role of mitochondrial phosphatidate in liver lipid metabolism. PMID- 1929412 TI - Modification of proteins by 3-hydroxyanthranilic acid: the role of lysine residues. AB - The mechanism of reaction of proteins with 3-hydroxyanthranilic acid (3OHA) under oxidizing conditions has been examined. A range of proteins were found to tan when exposed to oxidized 3OHA. One exception was lysozyme which tanned only after being denatured by reduction and carboxymethylation. Chemical modification experiments using bovine serum albumin (BSA) suggested that lysine was the primary site of reaction in 3OHA-mediated protein tanning. This reactivity of 3OHA toward lysine was confirmed by autoxidizing 3OHA in the presence of amino acid homopolymers. The rate of modification of both BSA and polylysine was pH dependent. At neutral pH, a component of the coloration of the protein was found to be due to the formation of a lysyl-p-quinone adduct. Other products appear to arise through addition to the 3OHA quinone imine. Poly-(Glu,Lys) was tanned by 3OHA at a greatly reduced rate, suggesting that electrostatic interactions may influence the reaction with lysine residues and may provide an explanation for the lack of tanning of lysozyme. Despite the reaction between 3OHA and lysine, amino acid analysis revealed little quantitative change in the lysine content of proteins even after exposure to 3OHA for a period of 24 h. These results support the proposal that reaction with lysine residues is the major route of protein tanning by 3-hydroxyanthranilic acid. PMID- 1929413 TI - Enzymatic recycling of oxidized ascorbate in pig heart: one-electron vs two electron pathway. AB - Enzymatic systems able to reduce either dehydroascorbate or ascorbyl radical back to ascorbate by "recycling" vitamin C may contribute to lowering the nutritional requirement of it and to increase tissue antioxidant capacity. The activities of two enzymatic activities, GSH-dehydroascorbate reductase (two-electron reduction pathway) and NADH-semidehydroascorbate reductase (one-electron reduction pathway) in pig tissues, have been investigated. The activity of glutathione-dependent reduction of dehydroascorbate, although measurable, appeared negligible taking into consideration the low physiological substrate concentration. On the other hand, the one-electron reduction of ascorbyl radical resulted fast enough to slow down the consumption of the antioxidant vitamin. PMID- 1929414 TI - Induction of 6a-hydroxymaackiain 3-O-methyltransferase and phenylalanine ammonia lyase mRNA translational activities during the biosynthesis of pisatin. AB - The isoflavonoid phytoalexin pisatin is synthesized by pea (Pisum sativum L.) in response to microbial infection and certain other forms of stress. The terminal step in the biosynthesis of pisatin is catalyzation by the (+)-6a hydroxymaackiain 3-O-methyltransferase (HMKMT). This enzyme, identified as a protein of Mr 43,000 by photoaffinity labeling (Preisig et al. (1989) Plant Physiol. 91, 559-566), was purified 280-fold from CuCl2-stressed pea seedlings and subjected to preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antibodies were raised in rabbit against this protein cut from the polyacrylamide gels. The antiserum against the purified enzyme inhibited HMKMT enzyme activity and showed high specificity for the Mr 43,000 protein on Western blots and in immunoprecipitations. This enzyme, present almost exclusively in the 95,000g supernatant after differential centrifugation, was induced in pea from a low constitutive level by treatment with CuCl2, suggesting that the HMKMT is newly synthesized in response to stress. HMKMT mRNA translational activity increased in peas with time after treatment with CuCl2. Peak translational activity occurred about 12 h after treatment, preceding peak enzyme activity by a few hours. Phenylalanine ammonia-lyase (PAL) mRNA abundance increased coordinately with that of HMKMT. The increase in PAL mRNA translational activity in response to stress is known to reflect transcriptional activation of PAL genes. Thus, the induction by stress of enzyme activity both at an early step and at the terminal step in the phenylpropanoid/isoflavonoid biosynthetic pathway appears to be at the transcriptional level. PMID- 1929415 TI - Ammonium ingestion prevents depletion of hepatic energy metabolites induced by acute ammonium intoxication. AB - Ingestion of an ammonium containing diet produces hyperammonemia and protects rats against acute ammonium intoxication. Acute ammonium toxicity has been attributed to the depletion of energy metabolite intermediates. We show here that hyperammonemia affords considerable protection against depletion of hepatic energy metabolites evoked by ammonium acetate injection. In control rats there were marked decreases in the content of acetoacetate, beta-hydroxybutyrate, ATP, 2-oxoglutarate, lactate, and pyruvate while phosphoenolpyruvate increased markedly. In hyperammonemic rats beta-hydroxybutyrate, ATP, 2-oxoglutarate, and lactate were not significantly affected while pyruvate increased markedly and phosphoenolpyruvate slightly. These results suggest that in controls the activity of pyruvate kinase is inhibited after ammonium injection while in hyperammonemic rats it is not inhibited. The content of alanine (an inhibitor of pyruvate kinase) reached 2.8 mumol/g in controls and 1.6 mumol/g in hyperammonemic rats, 15 min after ammonium injection. This could explain the different effects of ammonium injection on control and hyperammonemic rats. PMID- 1929416 TI - Extracellular poly(3-hydroxybutyrate) depolymerase from Penicillium funiculosum: general characteristics and active site studies. AB - An extracellular poly(3-hydroxybutyrate) (PHB) depolymerase has been isolated from Penicillium funiculosum cultural medium by a single hydrophobic column chromatography. The enzyme is a glycoprotein composed of a single polypeptide chain with a molecular mass of about 37,000 Da as analyzed by denatured sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by native gel filtration on Sephadex G-100. Its optimum activity occurs at pH 6.0. It has an isoelectric point of 5.8 and has a Km for PHB (average molecular weight = 45,000 Da) of 0.17 mg/ml. Various nonionic detergents competitively inhibit the enzyme with Ki values of 0.56 and 0.014% for Tween 80 and Triton X-100, respectively. The enzyme is extremely sensitive to diisopropyl fluorophosphate, mercuric ion, and dithiothreitol (DTT). However, sulfhydryl reagents have little or no effect on its activity. The inactivation by mercuric ion and DTT is reversible by mercaptoethanol and hydrogen peroxide, respectively. These data suggest that the enzyme may be a serine esterase and may contain an important disulfide bond. The enzyme is also inactivated by diazoacetyl and epoxide compounds at low pH, which can be prevented by PHB, indicating the presence of a critical carboxyl group at the active site. These characteristics of the enzyme are compared to other extracellular polymerases isolated from bacterial culture media. PMID- 1929417 TI - Multiple forms of human dopamine beta-hydroxylase in SH-SY5Y neuroblastoma cells. AB - Dopamine beta-hydroxylase exists as three forms in human neuroblastoma (SH-SY5Y) cells. The membrane-bound form of the hydroxylase contains three different species with apparent relative molecular weights of 73,000, 77,000, and 82,000. The intracellular soluble form of dopamine beta-hydroxylase was present as a single species with an apparent molecular weight of 73,000. Pulse-chase experiments showed that membranous dopamine beta-hydroxylase contains two subunit forms of 73,000 and 77,000 after short chase times. The soluble hydroxylase was synthesized as a single species of 73,000 at approximately the same rate as the lower molecular weight species of the membranous enzyme. A constitutively secreted third form of the enzyme with an intermediate apparent molecular weight also incorporated [35S]sulfate, whereas no significant amount of [35S]sulfate was observed in the cellular forms of the enzyme. The [35S]sulfate was incorporated on N-linked oligosaccharides. Approximately 12% of the enzyme is released constitutively within 1 h. These results demonstrate that neuronal cells have the ability to constitutively secrete a specific form of dopamine beta-hydroxylase which may contribute to the levels of this enzyme found in plasma. PMID- 1929418 TI - Regulation of phosphatidylserine decarboxylase in Saccharomyces cerevisiae by inositol and choline: kinetics of repression and derepression. AB - The biosynthesis of phosphatidylserine (PS) and its conversion to phosphatidylcholine (PC) are regulated coordinately by inositol and choline in Saccharomyces cerevisiae (G. M. Carman and S. A. Henry, 1989, Annu. Rev. Biochem. 58, 635-669). In this study, PS decarboxylase activity is shown to be partially repressed when inositol is added to the medium of cells in the log phase of growth, and the extent of repression is augmented by the inclusion of choline, but not ethanolamine. The kinetics of repression and derepression of PS decarboxylase, PS synthase, and phospholipid N-methyltransferase (PNMT) activities, as regulatory responses to the availability of exogenous inositol and choline, have been characterized. When inositol was added to the medium of cell cultures growing exponentially, the three biosynthetic enzyme activities reached an intermediate level of repression (50-85% of control) within 60 min. After the addition of the combination of inositol and choline, PS decarboxylase, PS synthase, and PNMT activities decreased to the intermediate levels of repression in 60 min and were subsequently reduced to 15-40% of control values during a later stage of regulation (2-3 h). In a derepression study, the three enzyme activities remained relatively stable for approximately 60 min following the removal of choline and/or inositol from the growth medium, but the specific activities of PS decarboxylase, PS synthase, and PNMT increased to maximally derepressed levels within 2-3 h. The induction of the three biosynthetic activities was blocked by cycloheximide, but not by chloramphenicol. In summary, the level of PS decarboxylase activity in S. cerevisiae is partially and reversibly suppressed by inositol and further diminished by the combination of inositol and choline. The biphasic kinetics of repression by inositol and choline suggest that the effect of choline is dependent on earlier events mediated by inositol and possibly involves a separate regulatory factor(s). PMID- 1929419 TI - The in vitro-synthesized precursor and mature mitochondrial aspartate aminotransferase share the same import pathway in isolated mitochondria. AB - Both the precursor and the mature form of mitochondrial aspartate aminotransferase were synthesized in a cell-free coupled transcription/translation system directed by the recombinant expression plasmid pOTS-pmAspAT and pOTS-mAspAT, respectively. Both newly synthesized forms of the protein were imported into isolated mitochondria, with the precursor correctly processed to the mature form. In both cases the import process showed resistance to externally added pronase and was abolished in mitochondria treated with the uncoupler carbonyl cyanide m-chlorophenylhydrazone. Moreover the imported products showed the same intramitochondrial localization as judged by a subfractionation procedure. In both cases import was time dependent and was completed in about 15 min. Finally a competitive inhibition of the import of the precursor of aspartate aminotransferase was found due to externally added purified aspartate aminotransferase. PMID- 1929420 TI - Structural study on a phosphorylated mannotetraose obtained from the phosphomannan of Candida albicans NIH B-792 strain by acetolysis. AB - A mixture of phosphorylated manno-oligosaccharides was isolated from the acid stable domain of phosphomannan of Candida albicans NIH B-792 strain (serotype B) by acetolysis and was fractionated on a column of Bio-Gel P-2 equilibrated with 50 mM pyridine-CH3COOH buffer, pH 5.0. A monophosphorylated mannotetraose was isolated as the major constituent. Structural analyses of this phosphate containing tetraose and its reduction product with NaBH4 by 1H, 13C, and two dimensional homonuclear Hartmann-Hahn NMR spectroscopies, subsequently, gave results consistent with the structure described below (where Manp represents the mannopyranose unit): [formula: see text] It was unexpected that the major phosphorylated branch in the acid-stable domain of the parent phosphomannan of this C. albicans strain is a relatively short mannotetraosyl residue containing solely alpha-1,2-linked mannopyranose units, and a phosphate group as a 6-O-ester on the intermediary unit adjacent to the nonreducing terminal group. These findings indicate that the size of the major phosphorylated branch of this phosphomannan is the same as that of Saccharomyces cerevisiae. PMID- 1929421 TI - Topology of O-linked N-acetylglucosamine in murine lymphocytes. AB - A unique form of protein glycosylation in which N-acetylglucosamine monosaccharides are O-glycosidically linked to serine or threonine residues (O GlcNAc) was initially reported in studies that used purified bovine milk galactosyltransferase to exogenously probe living populations of murine lymphocytes. However, in this same study, detergent latency experiments surprisingly indicated that unlike other known forms of protein glycosylation, O GlcNAc-modified proteins occur predominantly intracellularly. Since we now know that as little as 5% lysis could have accounted for the putative cell surface O GlcNAc seen in these earlier studies, and also in the light of recent data on the subcellular localization of the O-GlcNAc glycosyltransferase(s), we decided to critically reexamine the topology and polypeptide distribution of O-GlcNAc in primary cultures of murine lymphocytes that were prepared using improved cell selection techniques that do not involve complement-mediated lysis for cell enrichment. We have also examined two well-characterized T cell hybridoma lines. Under these highly stringent conditions of cell viability, we were unable to detect O-GlcNAc bearing proteins on the cell surfaces of any of these cell types. Also, O-GlcNAc was found on a similar subset of proteins in all of the various lymphocyte cell types. These data suggest that O-GLcNAc is highly restricted to the cytoplasmic/nucleoplasmic compartment of the cell and is found on a similar subset of nuclear and cytoplasmic proteins in functionally different types of lymphocytes. PMID- 1929422 TI - Homo- and heterotetrameric forms of the membrane-bound metalloendopeptidases meprin A and B. AB - Meprin A and B are disulfide-linked, tetrameric metalloendopeptidases in renal brush border membranes. Meprin A contains 90-kDa subunits (alpha subunits) and is expressed in random-bred and some inbred strains of mice. Meprin B contains subunits of 110 kDa (beta subunits) in situ, and the enzyme from C3H mice, a strain that does not express alpha subunits, has been characterized. Evidence from this and previous studies indicate that beta subunits are expressed in all mouse strains. The tetrameric organization of these meprins was examined in brush border membrane fractions from a random-bred strain (ICR) and two inbred strains of mice (C57BL/6 and C3H/He). Lectin blotting using biotinylated concanavalin A revealed that membranes from the random-bred strain contained three oligomeric complexes of approximately 390, 440, and 490 kDa as determined after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the absence of reducing agents. The subunits in all three oligomers were linked by disulfide bridges. Western blotting using an anti-alpha monoclonal antibody indicated that alpha subunits (90 kDa) were present in the 390- and 440-kDa complexes. Western blotting with a polyclonal antibody specific for beta subunits (110 kDa) indicated the presence of these subunits in the 440- and 490-kDa complexes. Electroelution of the individual oligomers followed by SDS-PAGE under reducing conditions confirmed that the 390- and 490-kDa molecules are homotetramers of alpha and beta subunits, respectively, and that the 440-kDa molecule is a heterotetramer consisting of disulfide-bridged alpha and beta subunits. C57BL/6 mice expressed both alpha and beta subunits and contained tetramers composed of alpha 4 and alpha 2 beta 2. C3H/He mice expressed only the 110-kDa beta subunits and the beta 4 oligomer. This type of multimeric organization of disulfide-linked subunits is unique for the known endopeptidases. PMID- 1929423 TI - Enzymological evidence for the indispensability of small intestine in the synthesis of arginine from glutamate. I. Pyrroline-5-carboxylate synthase. AB - The in vivo synthesis of arginine from glutamate in mammals requires seven enzymes to cooperate. Pyrroline-5-carboxylate synthase (PCS) is the first enzyme required. In order to establish the interorgan dependency of arginine synthesis, we quantitated PCS activity in as many as 32 rat tissues and found that the activity was concentrated only in the upper small intestine. Minor activity was found in pancreas, thymus, lymph node, and some other tissues: this was confirmed by the dependency on specific substrates, the loss of activity in the presence of an inhibitor, and identifying the reduced product as proline. No difference in activity was found between male and female rats on a milligram protein basis. The strict tissue localization of PCS and the localization of other enzymes of arginine synthesis previously reported clearly indicate that the upper small intestine is an indispensable tissue for the arginine synthesis from glutamate. Many of the tissues examined showed an activity to form an unknown product from glutamate. When assayed by the previously reported radiometric assay procedure using an AG1-X8 column (acetate), the product was not separated from PC and caused false-positive activities of PCS. An improved procedure was developed to overcome this technical difficulty. The new procedure enabled us to detect even 20 pmol PC without contamination by the adjoining unknown product. A preliminary characterization of the unknown product was achieved. PMID- 1929424 TI - Studies of ligand binding to Escherichia coli adenylosuccinate synthetase. AB - Dissociation constants of Escherichia coli adenylosuccinate synthetase with IMP, GTP, adenylosuccinate, and AMP (a competitive inhibitor for IMP) were determined by measuring the extent of quenching of the intrinsic tryptophan fluorescence of the enzyme. The enzyme has one binding site for each of these ligands. Aspartate and GDP did not quench the fluorescence to any great extent, and their dissociation constants could not be determined. These ligand binding studies were generally supportive of the kinetic mechanism proposed earlier for the enzyme. Cys291 was modified with the fluorescent chromophores N-(iodoacetylaminoethyl)-5 naphthylamine-1-sulfonate and tetramethylrhodamine maleimide in order to measure enzyme conformational changes attending ligand binding. The excitation and emission spectra of these fluorophores are not altered by the addition of active site binding ligands. TbGTP and TbGDP were used as native reporter groups, and changes in their fluorescence on complexing with the enzyme and various ligands made it possible to detect conformational changes occurring at the active site. Evidence is presented for abortive complexes of the type: enzyme-TbGTP adenylosuccinate and enzyme-TbGTP-adenylosuccinate-aspartate. These results suggest that the IMP and aspartate binding sites are spatially separated. PMID- 1929425 TI - Deamidation and succinimide formation by gamma-N-methylasparagine: potential pitfalls of amino acid analysis. AB - The biological function of the post-translationally methylated amino acid gamma-N methylasparagine (gamma-NMA) in proteins is unknown. We are examining the premise that amide methylation protects against deamidation. The free amino acids Asn, gamma-NMA, Gln, and delta-N-methylglutamine (delta-NMG) were incubated at elevated temperature and a variety of pH conditions to assay for deamidation. Gln disappears 12- to 14-fold more rapidly than delta-NMG, and Asn hydrolyzes to Asp and NH3 as expected. However, the gamma-NMA deamidation rate is severely overestimated by simply measuring the disappearance of starting material because gamma-NMA undergoes a cyclization reaction in preference to deamidation. At pH 1 the predominant gamma-NMA reaction is formation of stable 3-amino-N methylsuccinimide (NMS) and this occurs greater than 10-fold faster than Asn deamidation. At pH 4.0, 7.4, and 9.0 NMS is readily formed but it is unstable and partitions between the parent compound, gamma-NMA, and a second species, alpha-N methylasparagine. At pH 7.4 and 9.0 gamma-NMA disappears 4-fold slower than Asn but the methyl amide hydrolysis rate is diminished by as much as 13-fold. The Asn incubations over the pH range 1-9 yield scant evidence of a succinimide intermediate. It is concluded that the amide methylation provides a unique reaction pathway and stabilization for the N-methylsuccinimide species. Amino acid analysis by o-phthalaldehyde postcolumn reaction fails to detect isoasparagine, alpha-N-methylasparagine, and NMS. Amino acid analysis by precolumn derivatization with phenyl isothiocyanate destroys NMS and therefore cannot quantitate this compound. The ninhydrin postcolumn derivatization method is able to detect and quantitate all of these amino acid species. PMID- 1929426 TI - Development of pyrroline-5-carboxylate synthase and N-acetylglutamate synthase and their changes in lactation and aging. AB - Using newly developed assay procedures, we studied the development of pyrroline-5 carboxylate synthase (PCS) and N-acetylglutamate synthase (AGAS) activity in rat tissues. PCS in the small intestine of fetuses was 1/5 that of adults and reached an adult level as early as postnatal Day 1. The highest peak was observed at Day 14, and then activity decreased to the adult level. However, PCS in the brain was highest at birth and quickly inactivated in a few days. AGAS in the fetus small intestine was 1/3 that of adults and became higher than the adult level by 40% at Day 1 but was reduced to 1/2 that of adults at Day 3. Subsequently activity increased gradually to the adult level at Day 24. On the contrary, AGAS in the fetus liver was only 1/20 that of adults, and activity increased slowly up to 10 weeks and more. Pregnancy and lactation reduced liver AGAS markedly up to Day 8 and intestinal PCS considerably up to Day 14 after parturition. PCS in the small intestine of senescent rats was almost halved compared to young controls on a whole tissue basis. AGAS in the small intestine was also halved on a gram wet weight basis. Nonetheless the liver AGAS of 430-day-old rats was higher than that of the controls, although that of 630-day rats was lower. The results indicate that the arginine synthesizing enzymes in the small intestine are highly activated in suckling and weaning, and raise a question whether arginine remains fully dispensable in pregnancy, lactation, and senescence. PMID- 1929427 TI - Intracellular localization of newly synthesized transferrin receptors in the peripheral sheep reticulocyte. AB - In this paper, we provide evidence for an incompletely glycosylated transferrin receptor (TfR) which is not transported to the plasma membrane in the sheep reticulocyte. Cleveland peptide maps of the native (preexisting) TfR and [35S]methionine-labeled TfR were different. If the receptors were deglycosylated before mapping, the peptides were identical. There was preferential binding of the [35S]TfR to Con A-Sepharose, indicating the existence of a higher density of high mannose chains on the 35S-labeled TfR. Moreover, when total [3H]mannose labeled glycopeptides from reticulocytes were separated on a column of Bio-Gel P6, the [3H]mannose was associated with endoglycosidase H-sensitive high mannose or hybrid oligosaccharides, but not with complex sugars. After Percoll density gradient centrifugation, the [35S]TfR peaked in a fraction which separated from the bulk of the native TfR. The transmembrane glycoproteins, Band 3 and mature glycophorins, are not synthesized in the sheep reticulocyte. It appears that the reticulocyte, at this stage of red cell development, has lost the vesicles and/or proteins which are required to transport proteins from the site of translation to the cell surface. PMID- 1929428 TI - Purification and properties of NADP-linked glucose-6-phosphate dehydrogenase from Acetobacter hansenii (Acetobacter xylinum). AB - The NADP-linked glucose-6-phosphate dehydrogenase from Acetobacter hansenii (formerly known as Acetobacter xylinum) has been purified to apparent homogeneity. The sequence of the 10 N-terminal amino acids was determined. The subunit molecular weight of the enzyme is 53,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; gel filtration studies under nondenaturing conditions revealed that the molecular weight of the enzyme is 200,000 to 220,000 at pH 6.5 and 9.5, suggesting that the native enzyme is a tetramer. Specificity studies at both pH 6.5 and 9.5 demonstrated that the enzyme is a typical NADP-preferring glucose-6-phosphate dehydrogenase. The enzyme's catalytic activity increases with increasing pH, kcat being approximately 4 times greater at pH 9.5 than at pH 6.7 and the Km for NADP+ being 3 times lower at the higher pH; but the Km for glucose 6-phosphate is nearly 20 times higher at pH 9.5 than at pH 6.7, suggesting that the enzyme is catalytically more efficient at the lower pH. At pH 6.7, initial velocity measurements, product inhibition by NADPH, and inhibition by glucosamine 6-phosphate yielded results that were consistent with a steady-state random mechanism. At pH 9.5, steady-state kinetic analyses suggested that the mechanism is ordered, with coenzyme binding first, but nonlinear double-reciprocal plots were observed in the presence of NADPH when glucose 6-phosphate was varied and a complete kinetic analysis was not undertaken. Among several nucleotides and potential inhibitory ligands examined, only 2',5'-ADP inhibited the enzyme significantly. PMID- 1929430 TI - Trimethyllead acetate: a first-choice heavy atom derivative for protein crystallography. AB - The three-dimensional conformation of a protein provides a wealth of biochemical information and with the advent of cloning techniques that allow the preparation of proteins almost at will, a renewed interest has arisen in the crystallographic determination of protein structures. As in any research technique, however, there are often many difficulties encountered in an X-ray crystallographic investigation. One of these is the "phase problem." Although in recent years there has been considerable progress in the development of techniques for phase determination, including the use of molecular replacement and multiple wavelength measurements, the multiple isomorphous replacement method is still the most successful method for obtaining a three-dimensional structure. Here we report the use of trimethyllead acetate as a heavy atom compound of first choice in the preparation of an isomorphous heavy atom derivative. PMID- 1929429 TI - Functional expression of mammalian cytochromes P450IIB in the yeast Saccharomyces cerevisiae. AB - Three mammalian cytochromes P450 from the IIB subfamily, P450IIB11 from canine and P450IIB4 and P450IIB5 from rabbit, have been expressed in the yeast Saccharomyces cerevisiae by use of an autonomously replicating vector containing the galactose-inducible gal10 promoter. Cytochromes P450IIB4 and P450IIB5 are closely related proteins, with only 11 amino acid substitutions between them. P450IIB11 is a homologous protein, likely orthologous with IIB4 or IIB5, with 102 amino acid substitutions compared with the P450IIB4 protein and 106 compared with the P450IIB5 protein. The expressed proteins are functional in yeast microsomes, exhibiting activity toward androstenedione, 7-ethoxycoumarin, and, in some cases, progesterone. Expressed cytochromes P450IIB4 and P450IIB11 hydroxylate androstenedione with regio- and stereoselectivity characteristic of the purified, reconstituted proteins. A striking difference in the androstenedione metabolite profiles of IIB4 and IIB5 was observed, with IIB4 producing almost exclusively the 16 beta-hydroxy metabolite and IIB5 producing the 16 alpha-hydroxy and 15 alpha-hydroxy products. This is the first time that 15 alpha-hydroxylase activity has been associated with IIB4/IIB5. This activity has also been detected in liver microsomes from some, but not all, individual phenobarbital-induced rabbits tested and is largely inhibited by anti-rabbit P450IIB immunoglobulin G. These studies illustrate the utility of the yeast expression system for defining catalytic activities of individual mammalian cytochromes P450 and identifying new marker activities that can be utilized in liver microsomes. PMID- 1929431 TI - A reexamination of the properties of spinach nitrite reductase: protein and siroheme content heterogeneity in purified preparations. AB - Recent preparations of nitrite reductase do not display the heterodimeric quaternary structure obtained previously (total molecular weight 85,000; subunit molecular weights 24,000 and 61,000), but rather yield only the 61,000 molecular weight subunit, even when buffers containing the protease inhibitor phenylmethylsulfonyl fluoride are used. Nevertheless, such preparations retain the high ratio of ferredoxin-linked to methyl viologen-linked enzyme activity which has been previously taken as a characteristic of only the heterodimeric form. These preparations display a siroheme prosthetic group to protein ratio of 1.1. When nitrite reductase samples are frozen during the purification scheme, even though the ferredoxin-linked specific activity does not significantly decrease, enzyme activity-stained native gel electrophoresis of the subsequently purified protein reveals that gels with several bands of activity can be obtained. Further evidence of protein heterogeneity in these preparations comes from N-terminal amino acid analysis which reveals that even nonfrozen preparations contain two major peptides with valine and cysteine as the N termini. Formation of complexes of purified nitrite reductase with ferredoxin resulted in siroheme difference electronic spectra which resembled those observed previously for monomeric preparations. However, the siroheme midpoint potential of recent preparations of nitrite reductase (-287 mV) is close to that of the heterodimeric preparations. Ultrafiltration studies of crude extracts of the enzyme indicate that, at least at certain stages of the preparation, higher molecular weight forms of the enzyme may exist. We conclude that the 24,000 molecular weight polypeptide is a contaminant and that the heterodimeric quaternary structure model for spinach nitrite reductase is incorrect. Furthermore, the monomeric preparations we do obtain display both significant protein heterogeneity and facile loss of siroheme upon gel filtration. PMID- 1929432 TI - Isoelectric focusing of cytochrome P450: isolation of six phenobarbital-inducible rat liver microsomal isoenzymes. AB - A procedure for the isolation of native proteins from membranes by isoelectric focusing is described. It was used to resolve into six components the major fraction of cytochrome P450, obtained from liver microsomes of phenobarbital treated rats, after chromatography on DE-52 cellulose. When eluted from the gel, these proteins are in a native form as shown by (a) the light absorption spectra of the Soret region of their reduced carbonyl derivatives, all characterized by maxima around 450 nm, and (b) their enzymatic activities toward three different substrates. Characterization by a monoclonal antibody and partial sequence analysis of tryptic peptides reveal that three of the IEF-purified proteins have P450IIB1 character, whereas the other three are related to P450IIB2. PMID- 1929433 TI - Conformational dynamics of unfolded peptides as a function of chain length: a frequency domain fluorescence approach. AB - The fluorescence emission decays of single-tryptophan-containing peptides of different chain lengths in their unfolded state were investigated in the frequency domain. The data were analyzed using different functions, i.e., exponential fit and probability-density functions of different shape. We found that unimodal Lorentzian distributions best describe the fluorescence decays. This finding agrees with the point of view, now broadly accepted, that rapid motions exist in polypeptides. As a consequence of this flexibility, a large variety of conformations, with an unequal perturbation of tryptophan in its excited state, is generated. The lifetime distribution center was independent of the length of the polypeptide chain but strongly related to the nature of the amino acid residues located in the proximity of the tryptophan in the primary structure. The full width at half maximum, W, of the lifetime distribution was found to be related to the length of unfolded polypeptide by the empirical logarithmic relationship W = 0.83 log n, where n indicates the number of residues. For short peptides, a single lifetime or a narrow range of lifetimes is observed because of the fast relaxation of the tryptophanyl environment. On peptide lengthening, the spectrum of conformations, which the peptide can assume, increases; this causes a complex fluorescence decay represented by a lifetime distribution. For long polypeptide chains, the motions of the regions far from tryptophan do not significantly perturb the chromophore environment. PMID- 1929434 TI - Rat mast cell tryptase. AB - Rat mast cell tryptase is located largely if not totally in the cell's secretory granules. When the active site reagent [3H]diisopropyl fluorophosphate was used to label tryptase and chymase simultaneously, the ratio of tryptase:chymase active sites was determined to be 0.05. In comparison to chymase and tryptase in other species and chymase in the rat, rat tryptase is poorly bound to the granule matrix as evidenced by (1) its release parallel to histamine on induction of secretion and (2) its appearance in the supernatant when isolated granules were stripped of their membranes with hypotonic medium. Tryptase on release from the granule is moderately stable at a pH of 5.0 but unstable at pH 7.5, the pH that the enzyme encounters on secretion from the cell. These several properties indicate that the role of rat mast cell tryptase extracellularly is likely to differ greatly from that of chymase. PMID- 1929435 TI - Effect of ligand binding on the tryptic digestion pattern of rat brain hexokinase: relationship of ligand-induced conformational changes to catalytic and regulatory functions. AB - The Type I isozyme of rat hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is comprised of N- and C-terminal domains, associated with regulatory and catalytic functions, respectively. Extensive sequence similarity between the domains is consistent with evolution of the enzyme by gene duplication and fusion. Cleavage at tryptic sites located in the C-terminal domain is markedly sensitive to ligands present during digestion, while analogous sites in the N terminal domain are either resistant to trypsin or unaffected by the presence of ligands. These results imply a lack of structural equivalence between the N- and C-terminal domains, with the overall structure of the N-terminal domain being "tighter" and with a major component of ligand-induced conformational changes being focused in the C-terminal domain. Based on a previously proposed structure for brain hexokinase, protection by substrate hexoses is attributed to substrate induced closing of a cleft in the C-terminal domain. Similar protection at C terminal cleavage sites results from binding of inhibitory hexose-6-phosphates to the N-terminal domain. In addition, hexose-6-phosphates evoke cleavage at a site, T5, located in a region that has been associated with binding of ATP to the C terminal domain. Thus, alterations in this region, coupled with reduced accessibility resulting from cleft closure, may account for the mutually exclusive binding of inhibitory hexose-6-phosphates and substrate ATP. In the absence of Mg2+, all nucleoside triphosphates examined (ATP, UTP, CTP, and GTP) protected against digestion by trypsin. In contrast, ATP-Mg2+ stabilized the C terminal domain but destabilized the N-terminal domain, while the chelated forms of the other nucleoside triphosphates were similar to the unchelated forms in their effect on proteolysis; the unique response to ATP-Mg2+ reflects the specificity for ATP as a substrate. PMID- 1929436 TI - Structure-function relationship of lapemis toxin: a synthetic approach. AB - The synthetic approach to the structure-function relationship of lapemis toxin has been very useful in clarifying the important binding regions. To identify the neurotoxic binding domain(s) of lapemis toxin, several peptides were synthesized using the 9-fluorenylmethoxycarbonyl protocols. These peptides were based on the sequence of lapemis toxin, a 60-amino-acid, short-chain postsynaptic neurotoxin found in sea snake (Lapemis hardwickii) venom. The peptides were purified using high-performance liquid chromatography and sequenced to verify the correct synthesis, isolation, and purity. The synthetic peptide names and single letter sequences were Peptide A1 (15 mer) CCNQQSSQPKTTTNC Peptide B1 (18 mer) CYKKTWSDHRGTRIERGC Peptide B2 (16 mer) YKKTWSDHRGTRIERG Peptide C1 (12 mer) CPQVKPGIKLEC Peptide NS (20 mer) EACDFGHIKLMNPQRSTVWY. The peptide NS (nonsense peptide) sequence was arbitrarily determined and used as a control peptide. Biological activities of the synthetic peptides were determined by in vivo as well as by in vitro assay methods. For the in vivo assay, lethality was determined by intravenous injection in mice (Swiss Webster). For the in vitro assay, peptide binding to the Torpedo californica nicotinic acetylcholine receptor was determined. The peptides were found to be nontoxic at approximately 114 times the known LD50 of lapemis toxin. Binding studies with 125I-radiolabeled lapemis toxin and tyrosine-containing peptides indicated that lapemis toxin and peptide B1 bound the receptor, while the other peptides had no detectable binding. The central loop domain of lapemis toxin (peptide B1) plays a dominate role in the toxin's binding ability to the receptor. These results and the hydrophilicity analysis predict peptide B1 may serve as an antagonist or antigen to neutralize the neurotoxin effects in vivo. PMID- 1929438 TI - Lobster troponin C: amino acid sequences of three isoforms. AB - We have determined the amino acid sequences of the three major isoforms of lobster troponin C, using protein chemistry methods. Each isoform contains 150 amino acid residues, with a calculated Mr of 17,000 +/- 100. Sequence differences occur in all regions of the polypeptides, indicating that the isoforms are products of three different genes, rather than alternative transcripts of a single gene. Analysis of the sequences predicts that functional Ca(2+)-binding sites are present only in regions II and IV of four ancestral regions. PMID- 1929437 TI - Structural analysis of the N-linked oligosaccharides from murine glycophorin. AB - Glycophorins, isolated from BALB/c mouse erythrocytes, were degraded under mild and strong reductive alkaline conditions and the N-linked oligosaccharides were isolated as alditols. The oligosaccharide alditols were fractionated and purified using gel filtration, concanavalin A-Sepharose affinity chromatography, and high performance ion-exchange chromatography. Structural analysis was carried out by chemical analyses, periodate oxidation in combination with fast atom bombardment mass spectrometry, and 500-MHz 1H NMR spectroscopy. The results revealed the presence of sialylated biantennary, triantennary, and tetraantennary complex type oligosaccharides, all fucosylated at the innermost N-acetylglucosamine residue. The tri- and tetraantennary oligosaccharide-containing fractions also contained species elongated by one and/or two N-acetyllactosamine (-3Gal beta 1-4GlcNAc beta 1-) sequences. The N-linked oligosaccharides were shown to be combined only with one (the low molecular weight) of the two mouse glycophorins. PMID- 1929440 TI - [Mass screening for breast cancer in Japan]. AB - To establish effective mass screening projects for breast cancer, our study group (Tominaga group) was co-sponsored by the Ministry of Welfare. From 1968 to 1986, 643,513 women at the initial screening and 719,189 women at the subsequent screening were examined by physical examination. Abnormalities were found in 24,864 (3.9%) and 23,880 (3.3%) of these women, respectively. Cancer was detected in 833 women (detection rate 0.13%) and 428 women (0.06%), respectively. To establish the criteria for assessing the life-prolonging effect of mass screening for breast cancer, clinical stage and prognosis of breast cancer detected by mass screening were compared with those for matched patients in outpatients clinics. Early stages were significantly more common in the patients detected by mass screening. The 5-year survival rate was significantly higher in the patients detected by mass screening (91.7% vs. 85.6%; P less than 0.01), but the difference with the other group was not significant (80.5% vs. 78.1%). Women who had conducted breast self-examination (BSE) showed a higher survival rate than those who had not. We were not able to confirm the general belief that interval cancer is more aggressive in nature and shows a poorer prognosis than the cancer detected through periodic screening. PMID- 1929439 TI - Enzymological evidence for the indispensability of small intestine in the synthesis of arginine from glutamate. II. N-acetylglutamate synthase. AB - We describe here a concise assay procedure for N-acetylglutamate (AGA) synthase (AGAS) and its application to an extensive study of tissue distribution of AGAS activity. Crude mitochondria from several tissues were incubated in a pair of assay mixtures with [14C]glutamate in the absence and presence of acetyl-CoA at 15 degrees C for 10 min. Anionic components including [14C]AGA were first isolated from glutamate by a cation exchanger column. In order to remove anionic contaminants such as succinate, the AGA was converted to glutamate enzymatically by aminoacylase, and then the glutamate was isolated by cation exchange chromatography and counted. Recoveries were corrected individually. The difference between the pair incubations was taken as the activity. An extensive survey of AGAS activity in rats showed that, although the liver expressed the highest activity, the small intestine, testis, lung and submaxillary gland also exhibited considerable activity. Sexual differences in activity were not found in the liver and small intestine. We also detected activity in the human small intestine for the first time. Optimization of incubation temperature and time and the presence of arginine in an assay mixture was essential and we demonstrated that the AGAS reaction with crude mitochondria as an enzyme source was unstable without arginine and at higher temperatures. This procedure appears suitable for studying the physiological and nutritional role of AGAS in non-hepatic tissues. In the accompanying paper we applied this procedure to study the ontogeny of AGAS in developing rat tissues. PMID- 1929441 TI - [Mass screening of breast cancer with imaging diagnosis]. AB - Westernization of our life-style and diet has caused a higher incidence of breast cancer in Japan. Although mass screenings such as anamnesis, visual and palpable examinations are provided by local government in Japan, no curable cancer in the early stage can be detected without the use of imaging diagnosis. Furthermore, the image can be saved as a record. Mammography yields images that are best suited for breast cancer examination in terms of sensitivity, specificity and accuracy. However, the large volume of information collected from the images makes diagnosis extremely difficult. In order to ease the burden on the diagnosing physician and to reduce the examination cost, CRT diagnosis by digital images and image selection by an automatic diagnosis supporting system with neuro computer must replace the present filming method. On the other hand, 100% accuracy can not be achieved by either mammography or ultrasonic examination due to the limitation in depicting images on a display monitor. The accuracy rates of mammography and ultrasonic examination are 91.5% and 87.5% in our hospital. Imaging diagnosis, however, must be efficiently applied in addition to the visual and palpable examinations in promoting mass screening for breast cancer. PMID- 1929442 TI - [The status of colon cancer screening]. AB - Recent research into an early detection of colorectal cancers shows a surprisingly great progress. In 1991, Mr. Hisamichi reports that a mass screening method for colorectal cancers through immunological fecal occult blood tests may result in fewer fatalities due to colorectal cancers. This paper describes the current situations and future prospects of UICC workshops in principle, as undermentioned in 1 through 6. 1. The target population should be clearly defined and selected in such a way that, given the likely sensitivity and specificity of the test, an acceptable predictive value will be achieved. 2. As far as possible, the target population should be limited to those at particular risk of the disease in order to give a reasonable prevalence of detection when such individuals at risk can be identified. 3. There should be a reasonable expectation of reaching the target population and of achieving reasonable compliance in response to invitations to attend. The expected level of compliance should be stated. 4. There should be a reasonable expectation that recommendations for further diagnostic evaluation will be complied with by individuals who have a positive test. 5. There should be an agreed-upon policy on the classification of borderline abnormalities and also on their management, as well as on recommendations for their follow-up. 6. There should be a reasonable expectation that recommendations for appropriate management of lesions discovered by a screening program will be complied with both by the individual with the lesion and by the physicians responsible for his health care. PMID- 1929443 TI - [Fecal occult blood test and mass screening for colorectal cancer]. AB - It has become promising to establish a method for mass screening of colorectal cancer through the development of immunological fecal occult blood test. It has been shown that such tests have higher specificity and sensitivity compared to conventional chemical tests not only in cancer subjects and normal controls but in population screening trials. Further study is required to decide the optimal system within the framework of the screening such as the number of specimens, target age, and screening interval, etc. The efficacy of fecal occult blood screening remains to be shown in spite of the several randomized controlled trials completed or on-going. However, a case control study has strongly suggested that such screening would reduce the mortality from colorectal cancer. PMID- 1929444 TI - [Lung cancer screening--present status and the problems]. AB - For the counter measure having been indicated against increasing mortality rate in lung cancer cases, indication of lung cancer screening was started in 1987 in line with the law of insurance established for old aged people. In order to decrease the death rate in cases with lung cancer, methods of the counter measure were established for early detection of lung cancer by Chest X-ray and sputum cytology as well as early operative indication. Although results of these procedures have suggested effectiveness attained by mass screening, standard of efficiency have not been same in all the areas, where the screening having been performed, but there has been difference between respective areas, therefore, in order to make the every result of mass screening carried out in areas similar, it is necessary to make the indication of mass screening being done with careful attention for lung cancer cases. PMID- 1929445 TI - [Establishment of transplantable human colon cancer cell lines, chemosensitivity of colon carcinomas and the serially transplantable strains with MTT assay]. AB - Three human colon carcinoma xenografts serially transplantable into nude mice were established and named Co-6, Co-7, and Co-8. The chemosensitivity of these stains were assessed by MTT assay of the fresh surgical specimens (primary MTT assay) and the serially passaged xenografts (xenografts MTT assay), in vivo chemosensitivity test in nude mice (nude mouse system) and clinical responses. Drugs used for the experiments are mitomycin C (MMC), adriamycin (ADM), 5 fluorouracil (5-FU) and cisplatin (DDP). The primary MTT assay revealed true negative with MMC and 5-FU on Co-7 and Co-8 cases. The chemosensitivity of the tumor cells seemed to be increased in the xenografts MTT assay and nude mouse system, in which MMC and DDP were evaluated to be positive on Co-6 and Co-7. However, the chemosensitivity pattern of the tumor cells seemed to be stable in these chemosensitivity tests, indicating better to choose the agent with the highest inhibition rate among various tested agents, even when none have an inhibition rate equal to or more than 50%. PMID- 1929446 TI - [Antitumor activity of HO-221, a derivative of benzoylphenylurea against human cancer xenografts in nude mice]. AB - HO-221, a derivative of benzoylphenylurea, is a newly developed anticancer drug which was found to show an excellent antitumor effect against transplantable murine tumors by the novel mechanism of action. This study was designed to evaluate the antitumor effect of HO-221 and to establish the optimum regimen, using seven human gastrointestinal and breast cancers xenografted in nude mice. Better antitumor effect of HO-221 by oral administration was observed when it was suspended in larger volume of the vehicle. Moreover, the effect increased by the multiple intermittent administration compared to the single treatment. Best antitumor effect was observed by oral administration of 75 mg/kg (0.1 ml/10 g mouse body weight) repeated twice weekly for a total of eight times or 300 mg/kg (0.2 ml/10 g mouse body weight) repeated once weekly for a total of four times. The antitumor effects of these two regimens were approximately equal except against H-31, the former regimen being more effective. When the tumor growth inhibition rate (IR) over 58% was rated as "effective", the above two regimens were equally effective against 4 of 7 cancers, H-111, H-154, H-143 and H-31. While HO-221 was not effective to a gastric cancer line, H-81, which was most susceptible to the variety of existing anticancer agents, but effective to another gastric cancer line, H-111, which was relatively resistant to conventional cytocidal agents. From the aspect of chemosensitivity spectrum, this drug revealed a rather different pattern compared to other antimetabolites. Although oral administration volume is limited in small animal model, enhancing its antitumor effect may be possible in clinical application by contriving the method of administration. HO-221 is, thus, considered to be a promising drug for further study. PMID- 1929447 TI - [Combination chemotherapy of HO-221, a derivative of benzoylphenylurea with various anticancer agents against human cancer xenografts in nude mice]. AB - Antitumor effect of HO-221, a derivative of benzoylphenylurea, has been previously studied against seven human cancer xenografts in nude mice established and maintained in our laboratory. In this study, the effect of combination chemotherapy was examined with six of the above seven human cancer cell lines. These consisted of four gastric cancers (H-55, H-111, H-81 and H-154), one breast cancer (H-31) and one pancreatic cancer (H-48). HO-221 was used in combination with one of the following widely used anticancer drugs; mitomycin (MMC), adriamycin (ADM), CDDP, VP-16 and 5-fluorouracil (5-FU). When the tumor growth inhibition rate (IR) by combination of two drugs (at 1/2 MTD for each drug) exceeded both of IR obtained separately with single drug at 1/2 MTD, the combination regimen was rated as showing an additive effect. When IR by combination of two drugs at the same dose level exceeded both of IR obtained separately by MTD of each single drug, the regimen was rated as showing a synergistic effect. Histological changes and side-effects were also taken into consideration for the evaluation of the drug. Combination of HO-221 and MMC produced an additive effect against H-55 and H-111, a synergistic effect against H-81. In the treatment of H-31 which was highly susceptible to these drugs, a remarkable effect was shown in both IR and cellular changes even by combination using 1/2 MTD and 1/4 MTD doses. Combination with ADM at 1/2 MTD for both produced an additive effect against H-111 and H-48. Combination at MTD produced a marked antitumor effect against H-111 and a strikingly remarkable combination effect was confirmed. Combination with CDDP produced an additive effect against H 81 and a synergistic effect against H-154. Moreover, the weight loss by this combination regimen was far less than that by single administration of CDDP at MTD. An additive effect was demonstrated by combination with VP-16. Combination with 5-FU produced minimal combination effect. HO-221 was thus found to have a high antitumor effect by combination with various anticancer agents that are at present widely used clinically. HO-221 is expected to be a promising anticancer drug in its clinical application. PMID- 1929448 TI - [Study of pre-operative chemotherapeutic methods for colonic cancer--the concentration in blood and tissues after pre-operative administration of UFT]. AB - As one of the fundamental studies of the pre-operative chemotherapeutic methods in 22 cases with colonic cancer, we studied a progress of the concentration in blood and concentration in tissues including those in the portal vein after administration of UFT. The concentration of 5-FU in blood reached to the peak at 2 hours after administration of UFT and then decreased rapidly, while it was maintained for a long term in comparing with that of 5-FU (oral remedies; tablet and dry syrup). This fact suggested that UFT can be expected for metastatic inhibition and prevention of the recurrence because it showed an effect in free cancerous cells before and during operation. The anti-tumorous effect was also expected because the concentration of 5-FU in cancerous tissues was significantly higher than that in non-cancerous region. In our study in this time, down staging was considered by pre-operative chemotherapeutic method of colonic cancer in the future because concentration of 5-FU was also highly obtained in metastatic lymph nodes. From the above-mentioned results, pre-operative chemotherapeutic method using UFT was expected as a part of the intensive therapies. PMID- 1929449 TI - [Cisplatin, ifosfamide and vindesine in the chemotherapy of squamous cell carcinoma of the lung]. AB - Thirty-one patients with inoperable squamous cell carcinoma of the lung were treated with a combination of cis-platin (CDDP, 100 mg/m2 day 1), ifosfamide (IFX, 2 g/m2 day 1, 2, 3; with mesna) and vindesine (VDS, 3 mg/m2 day 1). The overall response rate (PR) was 71.0% with 22 partial responses. The median duration of response was 180 days. The median duration to show 50% decrease was 29 days. Myelosuppression and renal toxicity were severe. We concluded that the CIV regimen against squamous cell carcinoma of the lung was more effective yet more toxic than the other regimen containing CDDP and that candidates for this therapy must be carefully chosen. PMID- 1929450 TI - [Clinical effect of postoperative adjuvant chemotherapy for advanced colorectal cancer--comparisons of between tegafur (FT) and UFT]. AB - A randomized controlled study was conducted on a FT 600 mg/day daily oral administration group and a UFT 400 mg/day daily oral administration group as an adjuvant chemotherapy after curative operation for colorectal cancer patients with injection of Mitomycin 30 mg (20 mg during operation and 10 mg on the day following), and the results were examined. FT and UFT were administered orally for one year from the 3rd week after operation. The 5-year survival rate was slightly higher in the UFT administration group. Five-year survival was 82.7% for colon cancer and 82.1% for rectal cancer in the UFT administration group, against 72.6% and 72.0 % in the FT administration group. The same trend was observed when the survival rate was studied by various factors such as the size of tumor, depth of cancer invasion of the wall, histological type, lymph node metastasis, vascular invasion and the degree of progression. There was no difference between both groups in the patterns and times of recognition of the recurrences and in the appearance rate of side effects. The results suggest that UFT 400 mg/day is equal to or better than FT 600 mg/day in therapeutic effect for colorectal cancer patients, although the UFT dose is only 2/3rd the FT dose. PMID- 1929451 TI - [Pharmacokinetic study of etoposide in aged patient with non Hodgkin lymphoma receiving hemodialysis]. AB - A 78 year old patient with non Hodgkin Lymphoma receiving hemodialysis was treated with etoposide at a dose of 50 mg per body and its plasma pharmacokinetics were studied. The patient was dialyzed for 4 hours three times weekly. Etoposide was given by 60 minutes infusion on day 1 and 3, and hemodialysis was performed on day 2. The pharmacokinetic curve was found to fit to two compartment model. T 1/2 beta was 11.29 hours. Total body clearance was 13.65 mg/min/m2 on day 1 and 12.83 mg/min/m2 on day 3 respectively. AUC was 41.53 micrograms.h/ml on day 1 and 44.18 micrograms.h/ml on day 3 respectively. When these results were compared to those reported in patients with normal renal function, half life were longer while total body clearance was lower. In addition, AUC was higher. Hematologic toxicities were severe at this low dose. Hemodialysis did not influence on the decay of concentration during the elimination phase. These results suggest that it is necessary to reduce the dose of etoposide in hemodialysis patients. PMID- 1929452 TI - [Hepatic arterial infusion of farmorubicin (FARM) and 5-fluorouracil (5-FU) in a patient with massive hepatic metastasis from gastric cancer]. AB - A patient with massive hepatic metastasis from gastric cancer was treated with hepatic arterial injection of FARM and 5-FU one month after total gastrectomy. Response rate was 88% at 3 months after arterial infusion therapy. Severe side effects were not seen during treatment. It is suggested that the hepatic arterial infusion of combined FARM and 5-FU is a useful method for treatment of hepatic metastasis of gastric cancer. PMID- 1929453 TI - [Successful treatment of intrapericardial administration of carboplatin in a case of squamous cell lung cancer with malignant pericardial effusion]. AB - A 74-year-old male developed cardiac tamponade due to malignant pericardial effusion six months after he was diagnosed as primary lung cancer. Carboplatin was administered into the pericardial cavity six times with the total dose of 1,100 mg. Pericardial effusion disappeared without severe toxicities and response duration was about three months. Upon recurrence, he was again successfully treated with single intrapericardial administration of 300 mg of carboplatin. He survived for seven months after being diagnosed as cardiac tamponade. PMID- 1929454 TI - [Effect of UFT with high dose leucovorin for transplantable bladder tumor (MBT-2) in mice]. PMID- 1929455 TI - [Tumor markers--our experience. Tumor markers in ophthalmology]. PMID- 1929456 TI - Local therapies for cutaneous Kaposi's sarcoma in patients with acquired immunodeficiency syndrome. PMID- 1929457 TI - The use of immunohistologic analysis in differentiating cutaneous T-cell lymphoma from psoriasis and dermatitis. AB - BACKGROUND AND DESIGN: --Many investigators have applied immunohistologic analysis to skin biopsy specimens to distinguish cutaneous T-cell lymphoma (CTCL) from benign inflammatory diseases, such as psoriasis and dermatitis, which can clinically mimic early-stage CTCL. We studied the number and distribution of epidermal cells labeled with various monoclonal antibodies in normal skin and in psoriatic, dermatitic, and CTCL lesions by the immunoperoxidase technique. RESULTS: --Extensive staining of keratinocytes (KCs) with HLA-DR was seen in 27 of 41 patients with CTCL, but in only one of 14 patients with psoriasis and zero of 10 patients with dermatitis. CD2+ and CD3+ cells were present in the middle and upper epidermis of CTCL lesions in much greater numbers than in normal, dermatitic, and psoriatic skin. The percent epidermal area covered by CD1+ cells in psoriatic lesions (1.13%) and dermatitic lesions (1.65%) was significantly lower than that found in CTCL lesions (3.60%). CONCLUSION: --Epidermal immunohistologic patterns using anti-CD1, anti-CD2, anti-CD3, and anti-HLA-DR antibodies have the potential to distinguish CTCL from psoriasis and dermatitis in clinically ambiguous cases. PMID- 1929458 TI - Prognostic clinicopathologic factors in cutaneous T-cell lymphoma. AB - Influence of clinicopathologic data on survival was analyzed in 43 patients with cutaneous T-cell lymphoma. The median age was 66 years; 35 were male and eight female. The extent of the disease, established according to a modification of the TNM system, was as follows: T1, three patients; T2, 15; T3, 14; T4, 11; N0, 15; N1, 28; M0, 38; M1, 5; B0, 37; and B1, six. The first treatment applied after staging was skin-limited therapy in seven patients and different regimens of systemic chemotherapy in 29. Seven patients received no treatment or only topical corticosteroids and tars. Median follow-up was 26 months. Nineteen patients died, with a median survival of 36.3 months. The prognostic value of age, sex, delay of diagnosis and staging, pruritus, number of sites of clinically enlarged lymph nodes, results of staging and TNM classification, erythrocyte sedimentation rate, peripheral blood cell count, liver function tests, serum lactate dehydrogenase levels, protein electrophoresis, presence of epidermotropism, thickness of cutaneous infiltrate, blastic cell percentage, mitotic index, cellular density, cutaneous eosinophilia, and follicular mucinosis was studied. Multivariate analysis (proportional hazard model with covariates) indicated that the major prognostic factors in patients with cutaneous T-cell lymphoma are as follows: (1) in a clinical model, the T category of TNM classification and the serum lactate dehydrogenase value; and (2) in a clinicopathologic model, the T category of TNM classification and the thickness of cutaneous infiltrate (measured in 10(-1) mm from the granular layer to the lower limit of the infiltrate) of the clinically thickest lesion. PMID- 1929459 TI - HLA and epidermolysis bullosa. Association between the HLA complex and recessive dystrophic epidermolysis bullosa. AB - BACKGROUND AND DESIGN: --Epidermolysis bullosa refers to a group of genetic diseases characterized by marked skin fragility and blister formation following minor mechanical trauma. The patients with recessive dystrophic epidermolysis bullosa (RDEB) are the most severely affected with marked internal and external blistering, scarring, and death at an early age, secondary to malnutrition, septicemia, and/or metastatic squamous cell carcinoma. An association between RDEB and HLA antigens was explored in 28 patients with RDEB and their family members. RESULTS: --Our data demonstrate that susceptibility to develop RDEB may be associated with the HLA complex. The gene frequencies of DR4 and DQw3 were much higher in the patients than expected. These increases were likely due to statistically significant excess of DR4 and DQw3 homozygotes in the patients. In addition, the observed frequencies of two HLA haplotypes: Bw62, DR4, DQw3 and Bw60, DR4, DQw3 were significantly higher than expected. CONCLUSION: --If these observations are confirmed in the larger series of patients, the association between RDEB and HLA complex may have clinical utility in genetic counseling of siblings of child-bearing age who are at risk of being carriers of RDEB. PMID- 1929460 TI - N-acetyl-4-S-cysteaminylphenol as a new type of depigmenting agent for the melanoderma of patients with melasma. AB - BACKGROUND AND DESIGN: --Melasma is a difficult medical problem to treat. Hydroquinone is administered to many patients, but it is unstable and local irritation and dermatitis may develop after a prolonged use at a high concentration. This study introduces a new depigmenting agent, N-acetyl-4-S cysteaminylphenol, for better management of melanoderma in patients with melasma. RESULTS: --Our study, based on a retrospective observation of 12 patients using 4% N-acetyl-4-S-cysteaminylphenol in oil-in-water emulsion, showed a complete loss (8%), a marked improvement (66%), or a moderate improvement (25%) of melasma lesions. Visible changes of melanoderma can be seen in 2 to 4 weeks after daily topical application. This depigmentation was associated with a decrease in the number of functioning melanocytes and in the number of melanosomes transferred to keratinocytes. N-acetyl-4-S-cysteaminylphenol is the tyrosinase substrate, and, on exposure to tyrosinase, it formed a melanin-like pigment. CONCLUSIONS: --A phenolic thioether, N-acetyl-4-S-cysteaminylphenol, is a new type of depigmenting agent for the better management of melasma. It is much more stable and less irritating to the skin than hydroquinone, and it is specific to melanin synthesizing cells. PMID- 1929461 TI - Combined therapy for Sezary syndrome with extracorporeal photochemotherapy and low-dose interferon alfa therapy. Clinical, molecular, and immunologic observations. AB - Extracorporeal photochemotherapy is a well-tolerated treatment of palliative benefit for patients with the Sezary syndrome, but up to 25% of patients do not respond to this form of therapy. Interferon alfa is a glycoprotein with immunomodulatory properties that is also an active agent in the treatment of Sezary syndrome; however, dose-related toxic effects often limit its long-term use. A patient with rapidly advancing Sezary syndrome was treated with a combination of extracorporeal photochemotherapy and low doses of subcutaneous interferon alfa-2b. In addition to the almost complete clearing of his skin lesions and the marked diminution of his extensive lymphadenopathy after 16 weeks of combined therapy, disappearance of the malignant T-cell clone from the peripheral blood was documented by Southern blot analysis. Normalization of the peripheral blood lymphocyte phenotypic profile and an increase in natural killer cell activity were also observed. The excellent clinical response to combined therapy has been sustained, without adverse effects, during 18 months of treatment and 22 months of continued follow-up. The long-term disappearance of the malignant clone from the blood of a patient with Sezary syndrome in response to therapy has not been previously described and thus represents a novel observation. Extracorporeal photochemotherapy and low-dose interferon alfa are well-tolerated therapies that, when combined, may have additive efficacy in the treatment of Sezary syndrome. These results suggest that further exploration of this therapeutic combination is warranted. PMID- 1929462 TI - Reflex sympathetic dystrophy. Occurrence of inflammatory skin lesions in patients with stages II and III disease. AB - Reflex sympathetic dystrophy is a poorly understood syndrome of posttraumatic pain and sympathetic nervous aberration. We have observed previously unreported cutaneous manifestations of reflex sympathetic dystrophy. Seven patients with reflex sympathetic dystrophy were referred to our institution because of skin disorders. Three had recurrent ulcerating papules, and two had reticulate hyperpigmentation. Xerosis was common, and cutaneous atrophy was infrequent. Cutaneous ulceration and reticulate hyperpigmentation are previously unappreciated aspects of reflex sympathetic dystrophy. Further investigation regarding neural influences on the skin is warranted. PMID- 1929463 TI - Primary cutaneous Langerhans cell histiocytosis in an adult. AB - An unusual adult case of Langerhans cell histiocytosis is presented. The case initially mimicked granuloma annulare, both clinically and histologically. The patient subsequently had development of extensive cutaneous involvement that pathologically revealed a diffuse infiltrate of CD1-positive histiocytic cells containing Langerhans granules. Extensive investigations failed to detect systemic involvement. The patient's cutaneous eruption did not respond to various therapeutic interventions, including phototherapy with oral psoralen with long wave UV radiation in the A range (PUVA) and systemic vinblastine sulfate. Marked but temporary clinical and histologic improvement was achieved with total body electron beam radiotherapy. The nosology of this case is discussed in the context of the various histiocytic proliferative disorders. PMID- 1929464 TI - Cutaneous manifestations of human immunodeficiency virus infection. Part II. PMID- 1929466 TI - Dermatology in Australia. PMID- 1929465 TI - Recent developments in the pathogenesis of allergic contact dermatitis. AB - Allergic contact dermatitis is both an important clinical problem and a model system for lymphocyte-mediated pathologic changes. Elicitation of allergic contact dermatitis requires interaction of antigen with epidermal Langerhans cells, followed by migration of the Langerhans cells to the lymph nodes to present antigen to T lymphocytes. These activated T lymphocytes must then home to the antigen-exposed skin. Adhesion molecules such as LFA-1 and ICAM-1 have a role in this homing. Only a small proportion of the T lymphocytes in the skin lesion are specific for the inducing antigen. Studies of poison ivy (urushiol dermatitis) have determined this fraction to be less than one per 100 infiltrating lymphocytes. By a variety of amplification mechanisms, it is possible for this small number of antigen-specific T lymphocytes to induce the pathologic changes of allergic contact dermatitis. Improved understanding of this condition should result in increased knowledge of the pathogenesis of a variety of T lymphocyte-mediated skin conditions. PMID- 1929467 TI - Sclerodermoid plaques in a middle-aged man. Sclerodermoid porphyria cutanea tarda (PCT). PMID- 1929468 TI - Vesiculopustules of the thighs and abdomen. Subcorneal pustular dermatosis (Sneddon-Wilkinson disease). PMID- 1929469 TI - Multiple crusted plaques in a woman with systemic lupus erythematosus. Pemphigus erythematosus (PE). PMID- 1929470 TI - A woman with nodules and depressed scars. Lupus erythematosus (LE) profundus. PMID- 1929471 TI - Childhood bullous pemphigoid. PMID- 1929472 TI - Intravenous corticosteroids for systemic mastocytosis. PMID- 1929473 TI - The effect of the ice age on skin color. PMID- 1929474 TI - Hypocalcemia in impetigo herpetiformis: a secondary transient phenomenon? PMID- 1929475 TI - Chemotherapy-induced acral erythema showing vasculitic histologic features. PMID- 1929476 TI - Isolated plantar cerebriform collagenoma. PMID- 1929477 TI - Lichen amyloidosis in Alagille syndrome. PMID- 1929478 TI - Respiratory rate and pneumonia in infancy. PMID- 1929479 TI - Diagnosis of pneumothorax by echocardiography. PMID- 1929480 TI - Chronic vitamin D overdosage: a reminder. PMID- 1929482 TI - The paediatric departmental library. PMID- 1929481 TI - Fluconazole in neonatal disseminated candidiasis. PMID- 1929483 TI - Squatting and urinary tract infection. PMID- 1929485 TI - James Spence Medallist 1991, Professor John A. Davis. PMID- 1929484 TI - Paracetamol suppositories after cardiac surgery. PMID- 1929486 TI - Effects of parental divorce on children. PMID- 1929487 TI - Preschool vision screening in Cornwall: performance indicators of community orthoptists. AB - The performance of community orthoptists was retrospectively assessed in a primary preschool screening programme that has been established in Cornwall since 1982. The outcome of screening was compared between random samples of two birth year cohorts corresponding to the second and fourth years of existence of the screening programme (1980, n = 298 and 1982, n = 300). The mean age at screening was significantly later for the second cohort (4.3 years compared with 4.4 years) but otherwise performance indicators improved in the second cohort. Community orthoptists achieved a sensitivity of about 90% and specificity of 99% during the study. It is unlikely that the more commonly used two tier system of health visitors referring to a community orthoptist could achieve this degree of accuracy. PMID- 1929488 TI - Audit from preschool developmental surveillance of vision, hearing, and language referrals. AB - Referrals from preschool medical examinations were followed up for two years to assess attendance rate, waiting time for appointment, appropriateness of the referral, the diagnosis and management of the condition. Altogether 184 children were referrals for ophthalmology, 285 for audiology, and 195 for speech therapy. The median waiting time for an appointment was 46 days in ophthalmology, 175 days in audiology, and 83 days in speech therapy. The poorest attendance rate was identified in speech therapy (75%). Approximately 60% of examined children had a justified referral to ophthalmology and 20% had a clear defect. Over half the children in audiology (55%) had an altered impedance or hearing impairment. Of those with a hearing problem kept under review only half improved spontaneously. In speech therapy 80% of those assessed had a language problem. Many health problems were detected for which parents were unaware or did not use the service. Parental awareness alone will not uncover the sizable level of lingual and sensorial problems in inner city areas. This audit identified specific deficiencies in the provision of services and a number of organisational changes are suggested to improve their effectiveness. PMID- 1929489 TI - Multiple admissions under 2 years of age. AB - Hospital admission rates before 2 years of age are reported for two complete birth cohorts born within a geographically defined area five years apart in 1980 and 1985. Admission rates for individual children in the cohort before 2 years of age showed an increase between 1980 and 1985 from 209 to 247 children/1000. The most significant increase took place in those children admitted three or more times (multiple admissions). Children admitted once only increased significantly but there was no significant change in the number of children admitted twice. A total of 2.3% of the total cohort in 1980 and 3.6% in 1985 were admitted three or more times and accounted for over 30% of all admissions. Age specific rates are reported for the 1985 cohort; 36% of those admitted had their first admission before 3 months of age and 76% before their first birthday. The disproportionate contribution of children with multiple admissions to the admissions total renders admission data from Hospital Activities Analysis invalid unless linked to individual children. Cohort data based on a geographically defined population provide the most reliable admission rates and permit an accurate analysis of trends. The significance of and reasons for the upward trend in early childhood admissions are discussed. PMID- 1929490 TI - Nebulised water as a bronchoconstricting challenge in infancy. AB - The pulmonary response to inhalation challenge with nebulised distilled water was measured in 100 sedated infants with a history of wheeze. Lung function was measured by total body plethysmography. Satisfactory results were obtained in 88 infants. Fifty one were considered to have responded by developing a greater than 20% decrease in specific conductance (sGaw) after nebulised water. Thirty two of these infants had previously been challenged with nebulised saline before but only one showed a greater than 20% decrease in sGaw after saline. Twenty infants who developed signs of bronchoconstriction after challenge with nebulised water were rechallenged 20 minutes later. After the initial challenge a fall in sGaw of greater than 20% was found in 19 of the 20. After a second challenge with nebulised water only 15 (75%) showed a 20% or greater decrease in sGaw. Nine of the 20 infants remained sedated and were rechallenged for a third time. Eight showed a greater than 20% decrease in sGaw. This study indicates that approximately 60% of infants with a history of wheeze will bronchoconstrict in response to inhaled nebulised water and that up to 75% show no evidence of a subsequent refractory period to inhaled water challenge. PMID- 1929491 TI - Bronchial provocation determined by breath sounds compared with lung function. AB - Bronchial provocation testing with methacholine was undertaken in 15 children aged 5 to 8 years with obstructive lung disease, mostly asthma (13/15). The methacholine was inhaled during two minutes of tidal breathing in increasing concentrations. After each inhalation, lung function was measured and clinical signs recorded independently by two observers unaware of each other's results. The logarithm of the concentration of methacholine which caused wheezing over the trachea correlated closely with the logarithm of the concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (FEV1) but was 52% greater on average. At the end of the test there was a mean (SD) fall in FEV1 of 33.3 (7.4)% and a fall in oxygen saturation of 5.2 (3.1)%. Bronchial provocation testing by listening for wheeze over the trachea is a safe technique, which correlates with objective measures of lung function in young children. PMID- 1929492 TI - Compliance with treatment in asthma and Munchausen syndrome by proxy. AB - Among 1648 asthmatic patients, 17 families (1%) were identified as having Munchausen syndrome by proxy. Ten families did not treat their children's, attacks or refused medical care, and seven exaggerated the severity of symptoms to obtain invasive investigations and treatment. All the families had disturbed psychosocial backgrounds. The abuse consisted mainly of neglect, in that necessary treatment was not given. In some cases a more direct form of abuse was observed, when useless and sometimes harmful investigations and treatment were given. We conclude that medical control of the compliance of both parents and children is necessary in the management of childhood asthma. PMID- 1929493 TI - Attitudes of paediatricians to HIV and hepatitis B virus infection. AB - There is a recent upsurge of interest among health care professionals regarding the risk of accidental occupational exposure to HIV virus. We evaluated knowledge of virus carriage prevalence, needlestick injuries, venepuncture practices, and glove use among paediatricians in Wales and South West Regional Health Authorities. We also attempted to evaluate hepatitis B immunisation uptake in this group. Paediatricians have traditionally been considered a low risk group in the context of accidental occupational exposure to these viruses. We targeted a four point questionnaire at 221 paediatricians. Results suggested that despite recent increasing concern about these viruses, that is reflected in the amount of medical literature recently published, and the issuing of Department of Health guidelines on venepuncture, knowledge of prevalence of HIV and hepatitis B carriage rates, and hence assessment of risk magnitude, was surprisingly poor. Safe venepuncture practices were not widely used. In the 12 months before receiving the questionnaire 55% had suffered a needlestick injury with only 10% reporting the fact. Hepatitis B immunisation uptake was highest in the junior grades (but this does not necessarily mean those at greatest risk). There were many inconsistencies between the clinicians' perceptions of risk and their practices. As the virus attains a firm hold in the heterosexual population paediatricians by virtue of the nature of venepuncture in children will almost certainly see their risk of acquiring HIV/hepatis B viruses secondary to accidental occupational exposure increase over the next decade. Without an improvement in current knowledge of carriage prevalence in high risk areas and alteration in venepuncture practices/hepatitis B immunisation uptake some will unfortunately, though avoidably, contract these bloodborne viral infections. PMID- 1929494 TI - Sleeping position and rectal temperature. AB - The effects of sleeping position upon body temperature were assessed by continuous monitoring of rectal temperature in 137 babies sleeping at home under conditions chosen by their parents. There were three groups of subjects: (1) normal babies aged 12-22 weeks whose temperature rhythms were developed, (2) normal babies aged 6-12 weeks who were developing their night time temperature rhythms, and (3) babies the night after diphtheria, pertussis, and tetanus immunisation, whose temperature rhythms were disturbed. Sleeping in the prone position was not associated with higher rectal temperatures at any time of night in young babies, nor did it exaggerate the disturbance of rectal temperature rhythm after immunisation. In older normal babies the prone position did not disturb rectal temperature in the first part of the night, though prone sleepers warmed a little faster prior to walking, especially in warm conditions. Prone sleepers were, however, born earlier in gestation and tended to be of lower birth weight. Normal babies can therefore thermoregulate effectively whatever their sleeping posture, even in warm conditions, though the prone position may make it slightly more difficult to lose heat. It is difficult to see how the prone position, even interacting with warm conditions, could induce lethal hyperthermia in otherwise normal babies. Perhaps the prone position is associated with other risk factors for sudden infant death syndrome. PMID- 1929495 TI - Parental permission, information, and consent. AB - One hundred and fifty parents of emergency paediatric admissions were interviewed; 60 of 106 (57%) blood samples were taken and 107 of 120 (89%) treatment regimens were instituted without their permission. Furthermore, the reasons for over half the blood tests and 31% of the drug treatments were not explained. PMID- 1929496 TI - Dysequilibrium/ataxic diplegia with immunodeficiency. AB - A girl with purine nucleoside phosphorylase (PNP) deficiency is described. The nature of the motor disorder is similar to other children since found to have PNP deficiency. It is suggested that the diagnosis be considered in any child with unexplained dysequilibrium/ataxic diplegia. Other previously unreported features are intracytoplasmic neutrophil inclusion bodies and an improvement in the neutropenia after intravenous immunoglobulin. PMID- 1929497 TI - Fulminant hepatitis B in an infant born to a hepatitis Be antibody positive, DNA negative carrier. AB - A boy was born to a mother who was a chronic hepatitis B virus (HBV) carrier. She was hepatitis Be (HBe) antibody positive and HBe antigen and HBV-DNA negative. The boy had not received hepatitis B vaccine and died from fulminant hepatitis at 3 months of age. This case demonstrates the need to vaccinate babies of HBe antibody positive, HBe antigen negative carriers. PMID- 1929498 TI - Long term survival after heart transplantation for doxorubicin induced cardiomyopathy. AB - A 10 year old child developed severe cardiomyopathy after combined, multicycle chemotherapy for Ewing's sarcoma and was treated by heart transplantation with good results. Long term azathioprine and cyclosporin caused only mild impairment of immune function and there were no recurrent infections, local recurrences of the tumour, or distant metastases. PMID- 1929499 TI - Life threatening 'epilepsy'. AB - A 5 year old girl presenting with episodes of sudden loss of consciousness was found to have intermittent ventricular tachycardia and, on one occasion, self limiting fibrillation. Corrected QT interval was normal. After several therapeutic measures clinical and electrocardiographic improvement was achieved by administration of sotalol. PMID- 1929500 TI - Ultrafiltration for intractable ascites after liver transplantation. AB - A 5.7 year old boy with alpha 1-antitrypsin deficiency developed intractable ascites after liver transplantation. Conservative treatment was unsuccessful and after 18 days concentrated ascitic fluid was reinfused intravenously using a Gambro haemofilter. The ascitic loss resolved rapidly. This new method of ultrafiltration proved simple and effective. PMID- 1929501 TI - The Oregon formula: health economists' dream or Stalinist nightmare? PMID- 1929502 TI - Paediatric home care in the 1990s. PMID- 1929503 TI - Health care of American children. PMID- 1929504 TI - Aetiology of malocclusion of the teeth. PMID- 1929505 TI - Heart-lung transplantation for cystic fibrosis. 1: Assessment. AB - Forty five patients with cystic fibrosis (age 5-15 years) were assessed for heart lung transplantation between September 1987 and March 1990. The two main conditions for acceptance were (i) life expectancy less than 2 years and (ii) a severely impaired quality of life. Patients were accepted onto an active waiting list (n = 26), a provisional waiting list (n = 15), or not accepted (n = 4). Selection was made on clinical grounds with objective measurements used as an aid in assessment. As expected, the mean values for objective measures were significantly different between patients on the active waiting list compared with the provisional waiting list/not accepted group for resting heart rate (118/minute v 101/minute), percentage of ideal weight (83.2% v 93.1%), forced expiratory volume at one second as percent of predicted normal (27.3% v 47.6%), Shwachman-Kulczycki score (33.6 v 52.5), Chrispin-Norman x ray score (25.8 v 22.1), 12 minute walk (540 m v 854 m), and minimal oxygen saturation (81.5% v 92%). Psychological evaluation demonstrated a 55% incidence of individual and a 50% incidence of family morbidity. Of the 26 patients accepted onto the active waiting list, 11 have been transplanted (mean waiting time 3.3 months), 10 have died within a mean of 3.7 months of acceptance, and five remain on the active list (mean 5.6 months). PMID- 1929506 TI - Heart-lung transplantation for cystic fibrosis. 2: Outcome. AB - From March 1988 to March 1990, 11 children with cystic fibrosis (age 5-15 years) underwent combined heart-lung transplantation at our institutes. Maintenance immunosuppression consisted of cyclosporin and azathioprine with corticosteroids and antithymocyte globulin used perioperatively and during rejection episodes. Six patients (55%) survive from 1.5-23 months all of whom have improved life quality. Actuarial survival to 1 year was 55%. At six months after transplant, mean forced expiratory volume at one second was 73.5% of predicted normal, compared with 25% before transplant. There was one perioperative death, three later deaths associated with obliterative bronchiolitis at two, eight, and nine months, and one from mediastinitis at four months. Of the 15 children accepted for transplantation but not receiving grafts, 10 have died (eight within four months of being placed onto the transplant list). Early postoperative problems included acute reversible rejection (n = 10), meconium ileus equivalent (n = 3), and pancreatitis (n = 1). There was a high incidence of later pulmonary rejection with a mean of 5.7 episodes per patient in the first six months. Pulmonary infection occurred relatively infrequently, with Pseudomonas aeruginosa being the most common pathogen. Persistent diabetes mellitus requiring insulin occurred in four and systemic hypertension developed in one. PMID- 1929507 TI - Olivopontocerebellar atrophy of neonatal onset and disialotransferrin developmental deficiency syndrome. AB - Two brothers presented with olivopontocerebellar atrophy of neonatal onset. The clinical features (failure to thrive, hypotonia, liver disease, effusions, and visual inattention) were similar to those of the four cases already reported, as were the necropsy findings of olivopontocerebellar atrophy, hepatic steatosis and fibrosis, and microcystic renal changes. The clinical similarities between this and the disialotransferrin developmental deficiency syndrome were noted. The characteristic abnormality of serum transferrin found in the latter syndrome was also found in the two cases reported here. We suggest that both syndromes are caused by the same, or related, defects in glycoprotein metabolism. PMID- 1929509 TI - A dose ranging study of ibuprofen suspension as an antipyretic. AB - A double blind trial was conducted to determine the dose of ibuprofen suspension, which is effective in reducing the body temperature. The principal measure of efficacy was a reduction in axillary temperature of 1 degree C or more three hours after dosing. A second objective of the trial was to compare the incidence and severity of side effects and the palatability of a range of ibuprofen doses. Ninety three children were included in the analysis. All four doses of ibuprofen studied (0.625 mg/kg-5 mg/kg) were associated with temperature reduction and only the lowest dose failed to satisfy the principal measure of efficacy. The influence of dose on the magnitude of the body temperature reduction was significant and the 5 mg/kg dose achieved the largest mean reduction in body temperature (2 degrees C). The tolerability and palatability of all doses studied were excellent. These findings suggest that ibuprofen is a good alternative to paracetamol as an antipyretic. PMID- 1929508 TI - Normal postnatal androgen production and action in isolated micropenis and isolated hypospadias. AB - To try and find out if a defect in androgen biosynthesis or action could be responsible for the incomplete virilisation seen in boys with isolated hypospadias and isolated micropenis, androgen receptor binding was studied in genital skin fibroblasts established from 18 boys with isolated micropenis and 19 boys with isolated hypospadias. The production of gonadotrophins and testosterone was also measured in the boys with micropenis. There was no evidence of gonadotrophin deficiency, or of a defect in testosterone biosynthesis in the boys with micropenis, and there was no evidence of a quantitative or qualitative defect of androgen binding in either group. These isolated abnormalities may be the result of transient defects in androgen synthesis or action, or both, during a critical phase of embryogenesis. PMID- 1929510 TI - Accidents on hospital wards. AB - Eight hospitals reported 781 non-iatrogenic accidents occurring to patients and visitors under 16 years of age during an 18 month period up to October 1989. Accidents more often involved boys and children aged 3 to 5 years old. Falls from a height, slips, and striking accidents were common by day and falls by night. A total of 41% of accidents to inpatients occurred when parents were present. Only three accidents were serious. Altogether 27% involved beds and cots, and only one consequent injury was more than minor. Data collected routinely in case of medicolegal action can be presented in a form that may facilitate preventative work. Potentially remediable causes for concern include falls from beds and cots and the use of makeshift equipment. PMID- 1929511 TI - Natural history of asthma in childhood--a birth cohort study. AB - A cohort of 67 babies at risk of developing atopic disorders was followed up prospectively for 11 years. Clinical assessment and skin prick allergen sensitivity testing were performed annually over the first five years. At 11 years the cohort was restudied, symptoms were assessed by questionnaire, and bronchial reactivity (BHR) to histamine was measured. On the basis of skin testing, 35 children were atopic and 32 remained non-atopic. The expression of atopy increased with age. The lifetime prevalence of eczema, wheeze, and hay fever were 46%, 63%, and 56% respectively. The yearly period prevalence of hay fever increased with age, that of eczema declined, while that for wheeze showed a bimodal distribution with a peak before the age of 2 years and a gradual increase thereafter. Of the 21 children who wheezed before their second birthday, most never wheezed again and did not show BHR at 11 years. Of the 21 children whose first wheezing was after 2 years of age, 17 were still wheezing at 11 years and 12 showed BHR. Of the children who wheezed before 2 years of age, 10 were or became atopic, compared with 20 of the 23 children who wheezed at 11 years. These findings suggest that childhood asthma is a heterogeneous condition with atopy being strongly associated with the persistence of wheeze. PMID- 1929512 TI - Lipoprotein (a) concentrations as risk indicators for atherosclerosis. AB - The plasma concentration of different lipoproteins were measured in 102 control children, in 42 children with a parent suffering from coronary heart disease (CHD), and in 50 children with a parent with cerebrovascular disease (CVD). Significant differences between controls and children in the other two groups were found for apolipoprotein A I, apolipoprotein B, and high density lipoprotein cholesterol. Children of parents with CHD differed from controls in total cholesterol and apolipoprotein A II concentrations. A highly significant difference furthermore was found in lipoprotein (a) concentrations from children of parents with CHD in comparison with controls, but not between children of parents with CVD and controls. The difference in lipoprotein (a) concentrations (children of parents with CHD compared with controls) were only noticed in children above the age of 10 years. This could be explained by the observed rise of lipoprotein (a) between age 2 and 13 years, which was much more pronounced in the group with parents who had CHD. Plasma glycosaminoglycan concentrations were also measured in the three groups. They were significantly higher in children of parents with CHD and CVD compared with controls; they also varied with age. PMID- 1929513 TI - Panniculitis: a report of four cases and literature review. AB - Panniculitis is a disease with many causes and associations. The classification of clinical subtypes is unsatisfactory and hampered by the use of eponyms. Four children with recurring panniculitis are described and their histology presented. Three had subcutaneous fat atrophy with lobular panniculitis on biopsy; all responded well to corticosteroids. The fourth child had a septal panniculitis with no atrophy of subcutaneous tissues and only a partial response to treatment with corticosteroids. A widely accepted precise histological classification of panniculitis is needed to enable accurate predictions of the outcome of this serious disorder. PMID- 1929514 TI - Effect of salbutamol on oxygen saturation in bronchiolitis. AB - Inhaled sympathomimetic agents are often used in bronchiolitis with little objective evidence of benefit. The arterial oxygen saturation (SaO2) reflects the adequacy of ventilation-perfusion balance. The aim of the current study was to determine the effect of inhaled salbutamol on SaO2. In a randomised, double blind study, 21 infants, admitted with bronchiolitis positive for respiratory syncytial virus, had continuous SaO2 measurements made before and after nebulised salbutamol or placebo. SaO2 was recorded over 30 minutes for a baseline, then during the 10 minutes of first nebulisation with either salbutamol or saline, then over 30 minutes after nebulisation, the 10 minutes of second nebulisation with the alternate regime, and another 30 minutes after this second nebulisation. Desaturation occurred after salbutamol and saline nebulisation. The fall in SaO2 with salbutamol was seen whether infants received it as the first or second nebulisation. The fall in SaO2 after saline was seen when given first, but not when given after salbutamol. The decrease in SaO2 was greater and more prolonged with salbutamol than with saline. Routine nebulised aerosol sympathomimetic treatment during acute bronchiolitis cannot be recommended. PMID- 1929515 TI - Ultrasonography to diagnose and exclude intussusception in Henoch-Schonlein purpura. AB - Abdominal pain is a frequent symptom in the child with Henoch-Schonlein purpura and raises the suspicion of intussusception or perforation. One hundred and fifty two children with a diagnosis of Henoch-Schonlein purpura over 11 years were reviewed. Of these 60 had abdominal pain, 19 gastrointestinal bleeding, and nine were suspected intussusception. Intussusception was confirmed in two of these cases with ultrasonography. Ultrasound is an important tool in the early diagnosis of intussusception complicating Henoch-Schonlein purpura. Where the intussusception appears loose an expectant policy, with careful monitoring, may allow spontaneous reduction. It may also be used in monitoring patients for postoperative recurrence of intussusception, mural haematoma, and uncomplicated intestinal vasculitis with oedema. PMID- 1929516 TI - Partial splenectomy in sickle cell syndromes. AB - Partial splenectomy was carried out in four children with homozygous sickle cell disease and eight children with sickle cell beta thalassaemia. It was performed in order to preserve splenic contribution to the host defence against infections while suppressing hypersplenism or the risk of recurrence of acute splenic sequestration. Indications for this surgical operation were acute splenic sequestration (n = 1), hypersplenism (n = 5), and acute splenic sequestration and hypersplenism (n = 6). Surgery was uneventful in 11 patients. A significant reduction of blood requirements and a significant decrease of the number of hospitalisations/patient/year were observed after splenectomy. No recurrence of hypersplenism or acute splenic sequestration occurred and no severe infection was noticed during the follow up period after surgery (mean (SD) 4.2 (2.8) years; range 6 months-7 years). Mean haemoglobin concentration and leucocyte and platelet counts increased after surgery. The benefit of partial splenectomy compared with total splenectomy to treat acute splenic sequestration or hypersplenism in sickle cell disease is discussed. PMID- 1929517 TI - Focal nodular hyperplasia of the liver: a link with sickle cell disease? AB - Focal nodular hyperplasia is a benign liver tumour that is rare in children. We report the second case of a child with sickle cell disease presenting with symptomatic focal nodular hyperplasia. The possible pathogenesis of focal nodular hyperplasia and the association with sickle cell disease are discussed. PMID- 1929519 TI - Baby Check and the Avon infant mortality study. AB - Thirty seven sudden, unexpected infant deaths from the Avon study were scored retrospectively for serious illness using a modified version of Baby Check. Three cases (8%) scored very highly. In a small proportion of sudden deaths, Baby Check could have identified serious illness before death and led to hospital admission. PMID- 1929518 TI - Oxygen saturation in cystic fibrosis. AB - The availability of non-invasive oxygen saturation (SaO2) measurement could prove to be a useful tool for following up the progress of patients with cystic fibrosis. The present study was undertaken to compare its use with other routine measurements in the clinic. A total of 100 patients with cystic fibrosis were compared with 50 patients with stable asthma. The children were aged between 5 and 16 years and were studied as outpatients. A positive correlation was found between forced expiratory volume in one second and SaO2 in the group with cystic fibrosis and in the comparison group. Median SaO2 in those with cystic fibrosis (94.0%) was significantly lower than in controls (97.0%). Significant correlations were also found in the patients with cystic fibrosis for the following: Shwachman-Kulczycki score, higher weight centiles, and chronic pseudomonas lung infection with or without staphylococci. An inverse correlation was found with the Chrispin-Norman chest x ray score. SaO2 measurements are useful in the outpatient assessment of patients with cystic fibrosis and compare well with other standard tests of disease severity. PMID- 1929520 TI - Guillain-Barre syndrome in three siblings less than 2 years old. AB - Three of five children who were born to consanguineous parents developed Guillain Barre syndrome before they were 3 years old. The syndrome is rare in early childhood and we suggest that there may be a genetic element in the pathogenesis. PMID- 1929521 TI - Encephalomyelitis with seroconversion to Listeria monocytogenes. AB - A previously healthy girl recovered from a lymphocytic encephalomyelitis with brain stem involvement after antibiotic and steroid treatment. Cultures of blood and cerebrospinal fluid were negative, but she seroconverted to Listeria monocytogenes serotype 4. Antilisterial treatment should be considered in similar cases. PMID- 1929522 TI - No sensory neuropathy during pyridoxine treatment in homocystinuria. AB - Seventeen patients with cystathionine synthase deficiency homocystinuria were examined clinically and neurophysiologically for evidence of sensory neuropathy. All had received high dose pyridoxine (vitamin B-6) for many years. Absence of neurological disturbance in all cases suggests long term treatment with pyridoxine in the dosages used in homocystinuric patients is not harmful. PMID- 1929523 TI - Typhoid fever, ciprofloxacin, and renal failure. AB - An 11 year old boy from whom Salmonella typhi had been isolated was treated with ciprofloxacin. He developed non-oliguric acute renal failure that was treated successfully. PMID- 1929524 TI - How can the work of junior paediatricians be reduced? PMID- 1929525 TI - Quality assurance in the emergency room. PMID- 1929526 TI - Birthweight ratio. PMID- 1929527 TI - Survival and place of treatment after premature delivery. PMID- 1929528 TI - Non-invasive assessment of pulmonary arterial pressure in healthy neonates. PMID- 1929529 TI - Accuracy of height measurements. PMID- 1929530 TI - Prolonged low dose indomethacin for persistent ductus arteriosus. PMID- 1929531 TI - The incidence of renal calcification in preterm infants. PMID- 1929532 TI - Who pioneered the use of alternative donors (and stem cells from peripheral blood) in bone marrow transplantation? PMID- 1929533 TI - Major problems with pediatric bed usage statistics? PMID- 1929534 TI - Accidental poisoning in children. PMID- 1929535 TI - Children choking on foreign bodies from toys. PMID- 1929536 TI - Neonatal diaphragmatic paralysis caused by chest drains. PMID- 1929537 TI - Recessive ichthyosis congenita type II. AB - In the heterogeneous group of recessive congenital ichthyoses the disorder of desquamation seems to be a basic problem. Desquamation is strongly dependent on the normal lipid metabolism of the keratinocytes. We describe a group of patients who have a typical clinical picture of large scale ichthyosis and cholesterol clefts in the thickened corneal layer, evidencing a disturbance of the lipid metabolism of the skin. The corneocytes also show a thin or absent cornified envelope, which could indicate a disturbance of protein synthesis. These patients have a severe ichthyosis, but good general health and no associated symptoms. This disorder has recently been named 'ichthyosis congenita type II' by the Heidelberg group on the basis of electron microscopic findings. According to the present examination this group corresponds clinically to the currently used diagnosis 'lamellar ichthyosis'. PMID- 1929538 TI - Stratum corneum lipid abnormalities in atopic dermatitis. AB - Patients with atopic dermatitis (AD) often present with a dry skin. To clarify the relationship between dry skin and lipid abnormalities within stratum corneum, stratum corneum lipids were collected from six AD patients aged 15 to 25 years and from sex- and age-matched controls. All major stratum corneum lipid classes were separated and quantitated by high-performance thin-layer chromatography/photodensitometry. Six ceramide fractions were also isolated and quantitated by thin-layer chromatography/photodensitometry. Esterified fatty acids of both ceramide 1 (acylceramides) and wax esters were analysed by capillary gas chromatography. The relative amounts of all the stratum corneum lipid classes including squalene, cholesterol esters, wax esters, triglycerides, free fatty acids, cholesterol, ceramides, cholesterol sulphate and phospholipids did not differ statistically between AD patients and controls. However, a significant decrease in proportion of ceramide 1, which is believed to be a carrier of linoleate responsible for a water-barrier function, and increased levels of esterified C18:1 fatty acids (oleate) of ceramide 1 were observed in AD patients. On the other hand, the fatty acid compositions as well as the proportions of C16:1 straight-chain component in sebum wax esters of AD patients were very similar to those of controls. These results suggest that a significantly reduced amount and/or structural alterations of ceramide 1 deriving from epidermal keratinocytes may be responsible for the impaired water-barrier function of the skin in AD. PMID- 1929539 TI - Decreased specific anti-elastase activity in the uninvolved skin of patients with psoriasis. AB - Inhibitory activities against elastase, chymotrypsin and trypsin were studied in the fluid from experimentally developed suction blisters in the uninvolved skin of patients with psoriasis. These activities determined by spectrophotometry of specific synthetic low molecular weight substrates were compared with respective antiproteinase activities in sera of 32 patients with psoriatic lesions, ten patients in remission, and ten healthy volunteers. A marked reduction (29.2%) in the specific elastase inhibitory activity of blister fluid was found in patients with psoriasis when compared with normal subjects (p less than 0.05), since neither chymotrypsin nor trypsin inhibitory activities were altered. This reduction was despite about a 30% increase in the elastase inhibitory activity in the sera of these patients, which was related presumably to their increased activity of alpha 1-proteinase inhibitor, the main serum antiserine proteinase inhibitor. A decreased blister fluid:serum elastase inhibition ratio was shown in a large majority of patients with psoriasis, even in symptomless patients. The deficiency in specific elastase inhibitory activity of suction blister fluid was predominantly associated with early onset of psoriasis, guttate lesions and inactive lesions, skin involvement less than 20% of body surface, duration of relapse shorter than 2 months, and frequent relapses. These data indicate that the uninvolved skin of patients with psoriasis contains low concentrations of specific elastase tissue inhibitor, which deficiency might result in an excessive in vivo hydrolytic activity of neutrophil elastase released from migrating cells in the psoriatic skin. PMID- 1929540 TI - Skin levels of vasoactive intestinal polypeptide in atopic dermatitis. AB - Atopic dermatitis (AD) can be exacerbated by various factors, including emotional stress, scratching and sweating. The aim of the present study was to evaluate the hypothesis that the inflammatory reaction in AD is also neurogenic. For this purpose, the levels of vasoactive intestinal polypeptide were measured radioimmunologically in whole-tissue homogenates of lesional skin of 13 patients with atopic dermatitis. Radioimmunoassay was performed using an antiserum, AH78, recognizing the carboxy-terminal fragment vasoactive intestinal polypeptide (22 28). Vasoactive intestinal polypeptide immunoreactivity was detected in relatively low amounts in control skin (0.428 +/- 0.08 pmol/g tissue), whereas a marked increase in the peptide was observed in lesional skin of patients with atopic dermatitis (5.62 +/- 1.25 pmol/g tissue). These results seem to suggest that vasoactive intestinal polypeptide could have a pathogenetic relevance in skin lesions of atopic dermatitis. PMID- 1929541 TI - Trichophyton rubrum invasion of human hair apparatus in tinea capitis and tinea barbae: light- and electron microscopic study. AB - We have previously reported morphological changes of Trichophyton violaceum and Microsporum canis in hair apparatuses in tinea capitis. To investigate the morphology of Trichophyton rubrum in the human hair apparatus, two cases of tinea capitis and one case of tinea barbae were examined by light- and electron microscopy. The fungal elements, which were located in the lower keratogenous zone, showed non-septate hyphae in the outer part of the hair cortex. With the upward development of the hair layers, some hyphae invaded the keratinized hair cuticle and keratinized inner root sheath and were transformed into arthrospores. Some hyphae remaining in the hair cortex were also transformed into arthrospores, while other hyphae in the hair cortex did not survive, but degenerated. In T. rubrum hair infection, there is a distinct relationship between the morphological changes of the fungi and the hair cell differentiation as seen in T. violaceum and M. canis infections. However, T. rubrum displays unique morphological changes, which are different from those of T. violaceum and M. canis, in hair apparatuses. PMID- 1929542 TI - Histological demonstration of initial lymphatics in human skin: comparison between different extension techniques. AB - Initial lymphatic vessels (IL) are difficult to demonstrate histologically in excised normal skin, as they are usually completely collapsed. In this report three different methods (vacuum extension, large traction extension, and small traction extension) are described by which human skin specimens can be mechanically extended. After extension specimens were Epon enbedded and the IL counted and their diameters measured. The greatest number of lymphatic vessels was found in specimens extended by vacuum, and the smallest number in small specimens extended by traction. The highest density of lymphatic vessels was found 50-300 microns below the epidermis. Our data reveal that vacuum extension is useful for investigating questions concerning the topography of IL, whereas preparations extended by traction are more suitable for obtaining information about single lymphatic vessels. PMID- 1929543 TI - The severity of irritant contact dermatitis in various strains of mice correlates with endothelial expression of migration inhibitory factor (MIF). AB - Irritant contact dermatitis to croton oil in BALB/cByJ, C57Bl/6J and six recombinant inbred CxB strains of mice was investigated in relation to variations in endothelial migration inhibitory factor (MIF) reactivity. MIF has been shown to be a mediator of cellular immunity and operates as a differentiation signal inducing an inflammatory type of macrophage. The intensity of the ear swelling response reached a maximum 8 h after induction of contact dermatitis, with highest values in BALB/cByJ and CxB4/ByAH mice and weak reactions in CxB2/ByAE, CxB7/ByAK, C57Bl/6J and CxB1/ByAD mice. After the same time period (8 h) cryostat sections were immunostained for capillary endothelium expressing MIF. The most pronounced MIF expression was observed in BALB/cByJ mice, and CxB4/ByAH mice showed intermediate reactions and the other strains weak reactions. Endothelial MIF expression correlated well with the intensity of ear swelling (Pearson's correlation coefficient 0.82). Patterns of endothelial MIF expression in recombinant inbred strains suggest that endothelial MIF expression is not under the control of a single gene. Our data support the hypothesis that endothelial MIF expression plays a prominent role in inflammatory events and correlates with the severity of inflammation. PMID- 1929544 TI - Stimulation of anti-RNP antibody binding to cultured keratinocytes by estradiol. AB - Antibodies to extractable nuclear antigens (ENA) are frequently demonstrated in the serum of patients with cutaneous lupus erythematosus. To gain a better understanding of the influence of sex hormones on cutaneous lupus, we investigated the in vitro binding of anti-ENA antibodies to cultured human keratinocytes. Estradiol-beta augmented the binding of anti-RNP, anti-SS-A/Ro, and anti-SS-B/La antibodies to cultured cells, but produced no enhancement of the binding of anti-Sm antibodies. In addition, we examined the effects of 16-alpha hydroxyestrone, a highly estrogenic metabolite, on the binding of anti-ENA antibodies to cultured cells. This agent did not produce any augmentation of binding. Based on these experiments, we discuss the influence of estradiol on cutaneous lupus. PMID- 1929546 TI - Androgen regulation of a specific gene in hamster flank organs. AB - Flank organs of Golden Syrian hamster containing large sebaceous glands are a useful model for studying androgen-dependent gene expression. Recently, we have isolated an androgen-dependent gene from a cDNA library constructed from male mRNAs of flank organs. In the present study, using this gene as a probe, we examined the kinetics of loss and re-expression of the mRNA of this gene. Dot blot hybridization, the current method, can approximately quantify mRNA levels. Castration caused a marked decrease in the mRNA within a few days to undetectable levels. Topical application of testosterone re-activated the mRNA levels, with the earliest activation within 24 h. The results of various topical steroid applications showed a full re-activation of the mRNA by testosterone and dihydrotestosterone, partial re-activation by androstanedione and androstenedione, and no activation by androstanediol or dehydroepiandrosterone. Simultaneous application of testosterone and progesterone inhibited the expression of mRNA but application of dihydrotestosterone and progesterone did not. The current dot blot hybridization technique appears to be a more direct approach for studying androgen action on DNAs than other previously used methods such as morphometry or enzyme assay. PMID- 1929547 TI - Unusual distribution of melanocytes in hair bulbs from a Negro subject. PMID- 1929545 TI - Characteristics and modulation of dithranol (anthralin)-induced skin irritation in the mouse ear model. AB - Dithranol-induced skin irritation and the modulatory effects of different pharmacological agents were studied using the mouse ear model. A single topical application of dithranol caused a dose-dependent skin irritation which resulted in delayed swelling of the mouse ear with two separate peak responses, 1-2 and 6 10 days after application. The irritation was most effectively and persistently inhibited by topical treatment with corticosteroids, the free radical scavenger DL-alpha-tocopherol (DLAT) and the serotonin antagonist metergoline. The effect of corticosteroids, however, was slightly diminished during the second peak irritation. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), the dual lipoxygenase and cyclo-oxygenase inhibitor tolfenamic acid and the cyclo oxygenase inhibitor indomethacin as well as trifluoperazine retained their inhibitory activity. Of these compounds, indomethacin was active only during the first irritation peak, NDGA during both peaks and trifluoperazine principally during the second peak. Retinoic acid did not inhibit the ear swelling. The results confirm and extend the observations that the formation of free radicals is essential for dithranol inflammation. The inflammation can also be suppressed by inhibiting the formation of arachidonic acid or its pro-inflammatory metabolites. PMID- 1929548 TI - Allergic contact dermatitis--description of a test model for topical anti inflammatories with particular reference to the leukotriene-C4 antagonist Ro-23 3544. PMID- 1929549 TI - Study of HLA class I, class II and complement genes (C2, C4A, C4B and BF) in Japanese psoriatics and analysis of a newly-found high-risk haplotype by pulsed field gel electrophoresis. AB - Genetic polymorphisms of HLA antigens and HLA-linked serum complement components (C2, C4A, C4B and BF) were investigated in 79 Japanese patients suffering from psoriasis. HLA typing revealed increased frequencies of HLA-A1, A2, B39, Bw46, Cw6, Cw7 and Cw11. Among complement components, positive associations were obtained with C4A4 and C4B2 and a negative association with BFF. The major histocompatibility complex haplotype (supratype), HLA-A2-Cw11-Bw46-C2C-BFS-C4A4 C4B2-DRw8 is purported to be a new high-risk haplotype in Japanese patients with psoriasis. Analysis of patients with this supratype via pulsed field gel electrophoresis showed the existence of specific, extensive DNA deletions near HLA-DR genes, but no disease-specific patterns could be observed by means of this technique. The newly-found high-risk haplotype indicates racial and ethnic differences among psoriatic patients. PMID- 1929550 TI - Transcutaneous oxygen pressure in systemic sclerosis: evaluation at different sensor temperatures and relationship to skin perfusion. AB - Transcutaneous oxygen pressure (TcPO2) and skin blood flow (as evaluated by laser doppler) (LD) were investigated in 24 systemic sclerosis (SSc) patients in sclerotic skin (dorsal aspect of the hand) and non-sclerotic skin (interscapular region) and in 24 controls matched for sex and age for the same sites. The two parameters were evaluated at 44 degrees C (temperature of the two sensors) in 13 patients and 13 controls, and at 36-37 degrees C in the remaining 11. At 44 degrees C, TcPO2 was lower in SSc patients than in controls for both sclerotic and non-sclerotic skin. At 37 degrees C there was no significant difference. At 44 degrees C, LD values were decreased in patients with respect to controls for both sclerotic and and non-sclerotic skin. In contrast, at 37 degrees C the values were increased in patients only for the sclerotic skin. It can be hypothesized that the increased LD values at physiological temperature are at least in part balancing a decreased tissue oxygen tension, then a normal TcPO2 is ensured. On the other hand, the decreased LD values at 44 degrees C, when TcPO2 is also decreased, indicates that there is an inability of SSc vessels to significantly increase their flow under the stimulus of a maximal hyperaemia inducing temperature. PMID- 1929551 TI - Circulating androgens in male patients suffering from systemic scleroderma. AB - The excretion of collagen metabolites and circulating androgens was measured in ten males suffering from progressive systemic sclerosis. Significantly higher levels of sex hormone-binding globulin, total testosterone and dihydrotestosterone (DHT) (P less than 0.01), and total oestradiol (P less than 0.05), were found in patients when compared with age-matched controls. Urinary excretion of hydroxyproline in patients was found to correlate significantly with total testosterone (P = 0.035), with DHT (P = 0.005) and dehydroepiandrosterone sulphate (DHEAS) (P = 0.034). Similarly the hydroxyproline peptide fraction was found to correlate significantly with total testosterone (P = 0.037), with DHT (P = 0.005) and with DHEAS (P = 0.008). Hydroxylysine peptide in the urine correlated significantly with free testosterone (P = 0.035) and DHT (P = 0.040). Oestrogens did not correlate with urinary excretion of collagen metabolites. These findings suggest that androgens may play a role in the pathogenesis of scleroderma in male patients. PMID- 1929552 TI - In vivo and in vitro effects of glucocorticoids on lectin-induced blastogenesis in atopic dermatitis. AB - The effects of glucocorticoids administered in vivo and in vitro on lectin induced proliferation of lymphocytes sampled from venous blood were investigated in patients with atopic dermatitis (AD) and in normal controls. Stimulation by concanavalin A (Con A), phytohaemagglutinin A (PHA) and pokeweed mitogen (PWM) in patients and controls did not differ significantly under baseline conditions. After in vivo administration of methylprednisolone the decline of Con A-induced blastogenesis of leucocytes was similar in both groups, whereas PHA stimulation caused a significant reduction in the controls only. In vitro addition of different dexamethasone concentrations had a pronounced suppressive effect on Con A- and PHA-induced blastogenesis in both groups, whereas PWM stimulation was unaffected. Pretreatment in vivo with methylprednisolone further decreased the suppression of the Con A and PHA lymphocyte proliferation rate by dexamethasone added in vitro in controls but not in patients. With regard to B-cell proliferation generated by PWM, no consistent glucocorticoid effect could be observed. The impaired effect on lymphocyte blastogenesis of glucocorticoids administered in vivo, in contrast to a normal in vitro reaction to dexamethasone, together with recent findings of an altered glucocorticoid receptor pharmacology in AD, points to a decreased biological in vivo efficiency of methylprednisolone in atopic dermatitis. PMID- 1929553 TI - Peak blistering point: influence on fluid levels of 5-MOP in human skin in vivo after systemic administration. AB - The concentration of 5-methoxypsoralen (5-MOP) in suction blister fluid (SBF) after oral intake was determined in relation to the peak blistering point. Interstitial fluid was obtained from nine healthy male volunteers by applying mild suction (300-350 mmHg) to the skin of the volar aspect of the forearm. Blisters were raised at three different times: 18 h prior to drug administration (group I); 2 h prior to drug administration (group II); and during drug ingestion (group III). SBF levels of 5-MOP were determined in each group of blisters 2 h after oral administration of 1.2 mg/kg micronized 5-MOP. The results showed a statistically significant difference in the concentrations of 5-MOP between each group of blisters. The highest concentration of 5-MOP in the SBF was found in group III and the lowest in group II blisters. These findings suggest that the point of peak blistering in relation to drug administration needs to be known in each pharmacological study using suction blisters. PMID- 1929554 TI - 1-2B7B: monoclonal antibody reacting to the 120 kDa polypeptide component of human epidermal hemidesmosomes. AB - Immunohistochemical and immunochemical analyses were performed on a monoclonal antibody designated 1-2B7B which was derived from immunizing mice with human prostate epithelial tissue. The 1-2B7B antigen was expressed not only along the acinous basement membrane zone (BMZ) of the prostate and testis, but also along the BMZ of the epithelia of several other organs including the skin, oesophagus, urinary bladder, ureter, stomach, intestine and bile duct. The antigenic epitope was not expressed in these tissues of lower mammals. Immunoelectron microscopic studies on normal human skin revealed that the 1-2B7B antigen was localized mainly just beneath the hemidesmosomes of basal keratinocytes, but not beneath melanocytes. Indirect immunofluorescence and immunoelectron microscopic studies on 1 M NaCl-split skin confirmed that this antigen was not separated from the cytoplasmic membrane of basal cells after salt treatment. SDS polyacrylamide gel electrophoresis of immunochemically purified protein from the epidermis demonstrated the molecular weight of the antigen to be 120 kDa. 1-2B7B monoclonal antibody should be a useful probe for studying the pathomechanism of some blistering diseases, as well as the assembly and function of the epidermal-dermal junction. PMID- 1929555 TI - Reduced superoxide dismutase activity in UVB-induced hyperproliferative pig epidermis. AB - Decreased superoxide dismutase (SOD) activity has been reported in various hyperproliferative keratinocytes. In order to elucidate the relationship between epidermal SOD activity and keratinocyte proliferation, we employed in vivo UVB irradiation. Following UVB irradiation at twice the minimum erythema dose, pig epidermis revealed an initial decrease in thymidine incorporation and mitotic counts for at least 48 h, followed by a marked increase, the peak of which was observed at 96 h after irradiation, and a return to basal levels by 5-7 days. The SOD activity remained constant during the initial 48 h and then decreased to about 50% at 96 h, mainly due to a decreased Cu,Zn-SOD activity. Our results indicate that the increased keratinocyte proliferation induced by UVB irradiation is accompanied by a decrease in SOD activity, and that this decrease is mainly due to a decreased Cu,Zn-SOD activity. No alteration in SOD activity was noted during the initial hypoproliferative phase following irradiation. PMID- 1929556 TI - Repeated treatment with dithranol induces a tolerance reaction in keratinocytes in vitro. AB - The hyperproliferative human keratinocyte line (HaCaT) was tested for dithranol tolerance (tachyphylaxis) at the cellular level. At day 4 after seeding, keratinocytes were treated with 0.3 or 1.0 microM dithranol. Data were compared with those from experiments including additional pretreatments with 0.3 microM at day 3, or at days 1 and 3. Protein content, DNA synthesis and protein synthesis (incorporation of 3H-thymidine and 14C-amino acids per protein) were determined at 24, 48 and 72 h after the last drug exposure. Protein content of attached cells decreased in relation to dose and frequency of treatments. Inhibition of DNA and protein synthesis (38.2% and 32.3%, respectively) also occurred 24 h after a single treatment with 0.3 microM dithranol, but was only 18.4% and 9.1% after pretreatment twice with 0.3 microM dithranol. This tolerance reaction in vitro, after repeated dithranol exposure of human keratinocytes, may be explained by a selective loss of drug-sensitive cells. PMID- 1929557 TI - In vitro comparison of water-holding capacity of the superficial and deeper layers of the stratum corneum. AB - We measured the electrical conductance at 3.5 MHz of a sheet of normal stratum corneum (SC) mounted with either the upper surface or the lower surface downward in simulated in vivo conditions. In this way, we assessed the water-binding capacity of the upper and lower portions of the horny layer. Measurements were made with the SC model in environments of various relative humidities. Between 30% and 90% relative humidity, the conductance of the upper surface was always significantly higher than that of the lower surface. In contrast no significant difference was observed in transepidermal water loss (TEWL) with the SC sheet placed upwards or downwards. After exposure to lipid extraction with acetone/ether, a significant decrease in conductance and increase in TEWL occurred, particularly in the upper surface. The amount of extractable amino acids was much higher from the middle layer than from the outer layers of the SC, and was lowest from the deepest part of SC. These results, indicating a lower efficiency of the lower surface of the SC for water-binding than the desquamating upper surface, suggest that newly formed immature SC does not have the water holding capacity of the mid portion of the SC, which is probably the layer with the greatest water holding capacity. PMID- 1929558 TI - Correlation between HLA-A2-Bw46-DRw8 haplotype and increased levels of complement components (C4 and C4a) in patients with psoriatic arthritis. PMID- 1929559 TI - Demythologizing rural mental health. PMID- 1929560 TI - Sibling grief: a case report. AB - The intensity of sibling grief and the significance of sibling mourning are described in research studies. Yet, nurses caring for dying children may be unaware of these findings and may not offer adequate support to assist siblings in working through grief. This article details one child's perceptions of the loss of a brother and provides rich clinical material for understanding typical sibling responses. The description of the therapy sessions provides a model for working with siblings and demonstrates the value of art as a therapeutic medium. These strategies are useful for nurses working with grieving siblings and may be applicable to other situations in which children experience a significant loss. PMID- 1929561 TI - Nursing-led group modalities in a psychiatric inpatient setting: a program evaluation. AB - This examination of group practice activities conducted by nurses in an inpatient setting combined retrospective examination of practices and concurrent analysis of what is actually done on the units. The most striking finding of this evaluation of institutional nursing-led or co-led group activities was the significant decline in the number of groups. Second, and a related finding, was the need to standardize the format for documenting group activities and outlining the scope and function of these groups. And finally, the need for concise evaluation criteria and measures to document the achievement of stated patient outcomes was very apparent. PMID- 1929562 TI - Borderline personality disorder and group therapy. AB - This study examined the process and outcome of group therapy for community health center clients with borderline personality disorder. The results indicated that group members rated Yalom's curative factors to be increasingly helpful over time, and that universality and existential factors were consistently ranked as very helpful group process variables. The group sessions also were associated with positive outcomes, as evidenced by significant improvement in Goal Attainment Scale scores and the depression and hostility scales of the Brief Symptom Inventory. The results of this study suggest that group therapy is a valued and effective treatment option for people with borderline personality disorder. PMID- 1929563 TI - Cognitive therapy of anger management: theoretical and practical considerations. AB - Cognitive therapy, known for its treatment of depression, is fast becoming an approach to treating a wide variety of psychosocial phenomena. This article explores a model for anger management that incorporates elements of cognitive theory. The basic premises of cognitive theory will be presented. The application of these premises to the control of anger will be discussed. The anger arousal hypothesis by Novaco provides the foundation for the theoretical and clinical issues pertinent to psychiatric mental health nurses. PMID- 1929564 TI - Outpatient psychogeriatric nursing services: an integrative model. AB - The complex needs of psychogeriatric patients and their families require specialized outpatient psychogeriatric services. The interaction of physical and mental health and the need for coordinated care places important responsibilities on nursing because it contributes to integrated, multidisciplinary care delivery to these patients and their families. This article presents a model of outpatient psychogeriatric nursing services focused on the community integration of patients and families. Experiences in the development of the Geriatric Neuropsychiatry Clinic at the University of Virginia, Charlottesville, are used as the point of departure from which to describe a model of outpatient psychogeriatric nursing care delivery that is multidisciplinary, clinically innovative, and epidemiologically justified. PMID- 1929565 TI - Psychological correlates of loneliness in the older adult. AB - Loneliness is the emotional response to the discrepancy between desired and available relationships. As people grow old, the likelihood of experiencing age related losses increases. Such losses may impede the maintenance or acquisition of desired relationships, resulting in a higher incidence of loneliness. This pilot study examines how loneliness relates to age-related losses, hopelessness, self-transcendence, and spiritual well-being in a convenience sample of 107 adults aged 65 years or older. The collective utility of the independent variables in predicting loneliness was investigated by means of a regression decision tree with an automatic random subset crossvalidation procedure. This procedure explained 46% of the variance. Higher scores for age-related losses and hopelessness were associated with higher loneliness scores. Higher scores for self-transcendence and existential spiritual well-being were associated with lower loneliness scores. PMID- 1929566 TI - Sobriety, friends, and gay men. AB - The purpose of this study was to learn how sobriety affected friendship circles of gay men recovering from alcoholism. Twenty gay recovering alcoholic men, each with at least 1 year of sobriety, were interviewed in depth. Before sobriety, the typical picture portrayed by the men was that of losing friends, having many heavily drinking acquaintances, and having difficulty meeting the responsibilities in friendships. In sobriety, the typical gay man realized that most of the gay men that he had thought were his friends were actually only drinking buddies. As sobriety time lengthened, the men reported expanding their friendship circles to include primarily gay men of Alcoholics Anonymous and others who were either normal drinkers or abstainers. Finally, nursing implications of this study are discussed. PMID- 1929567 TI - Goal setting and recovery from alcoholism. AB - Evaluation of alcoholism treatment effectiveness needs to be based on the healthy goals that alcoholics themselves identify as important. This research uses ethnography and grounded-theory methods to develop a model of recovering alcoholics' goal progression. The author spent 28 days in a treatment center, engaging in all patient activities, and observed and interviewed 42 participants to determine what they wanted from treatment. The research indicates that recovering alcoholics' goals develop through four stages. Certain kinds of behavior must be accomplished for an alcoholic to move from one stage to another. Behavior that facilitates and inhibits goal progression is identified. PMID- 1929568 TI - A behavioral comparison of the helping styles of nursing students, psychotherapists, crisis interveners, and untrained individuals. AB - Helping styles of nursing students were compared with those of subjects in a prior study (17 psychotherapists, 12 crisis interveners, and 15 untrained people). Subjects were 30 junior-year college students in the second part of a two-course sequence in interpersonal relations. The subjects were videotaped in a 3-minute interaction with a simulated client. An experienced psychotherapist who was trained in the use of the Helping Skills Verbal Response System instrument rated each student. The helping behaviors of nursing students were found to resemble those of trained mental health practitioners; their behavior was significantly different from those of untrained individuals, who were highly verbose, directive, and used minimal reflection of affect or content. PMID- 1929569 TI - [Acute malignant myelofibrosis. Report of 3 cases]. AB - This report describes three cases of acute malignant myelofibrosis characterized by pancytopenia, absence of splenomegaly, bone marrow fibrosis with an immature cell proliferation and rapidly fatal outcome. The authors investigated the origin of blast cells with the use of immunohistochemical markers on paraffin embedded material with anti-factor VIII, BNH9 and anti-lysozyme. They studied the expression of megakaryoblastic, erythroblastic and myeloblastic differentiation in these cells. They demonstrated the heterogeneity of blast cells which are capable of differentiating along the three hematologic cell lines. The morphometric study showed the mutilating or systematized character of myelofibrosis. The increase in reticulin fiber density compared with normal bone marrow was not significantly different from two other types of myelofibrosis. It would be interesting to correlate a quantitative parameter with the course of this disease in order to evaluate the prognosis and the treatment. PMID- 1929570 TI - [Malacoplakia of the vagina. Cytological, histological and ultrastructural study of a case]. AB - A case of vaginal malakoplakia is reported in a 65 year old patient receiving prednisone for fifteen months for the treatment of collagen colitis. The macroscopic and microscopic appearance, cytological examination of the vaginal smear and ultrastructural examination were typical of malakoplakia. To our knowledge, this is the seventh detailed case of vaginal malakoplakia and the twenty-sixth case of malakoplakia of the female genital tract. PMID- 1929571 TI - [Hodgkin's disease: epidemiological and anatomopathological aspects]. AB - Only seventy cases of Hodgkin's disease were reported in Cameroon over a twelve year period (1979-1989), which represents about six cases a year. Hodgkin's disease therefore seems to be rare in Cameroon where it will be useful to follow its epidemiological course. At the present time, 81.5% of patients are male and children aged 10 to 19 are mostly affected. Type I (lymphocytic predominance) is the more frequent, representing 40% of cases. Biopsy leading to the diagnosis is mainly performed on cervical lymph nodes (58% of cases). PMID- 1929572 TI - Large intramural cyst of the uterus. Report of a case. AB - A case of a rare lesion, i.e., congenital intramural cyst of the uterus, is reported. The diagnosis of paramesonephric cyst was suggested on the basis of histopathologic, histochemical and immunohistochemical findings. The literature is reviewed and the differential diagnosis of this lesion is discussed. PMID- 1929573 TI - [Splenolymphatic plasmacytoma in AIDS]. PMID- 1929574 TI - [Cardiomyocyte in valvular cardiopathies. Comparative morphometry of myofibrils and mitochondria. Functional correlations]. AB - Twenty-four endomyocardial biopsies performed during surgical correction of valvulopathies were compared with ventricular function. Patients were divided into three groups: group I without anomalies of ventricular function, group II with a slight decrease of the ventricular ejection fraction, group III with a low ventricular ejection fraction. Morphometric analysis was carried out using electron microscopic photographs and an image analyser. The results were correlated with those of functional studies. In patients of the second group, the small number of mitochondria with respect to the increased myofibrillary area seemed to indicate mitochondrial dysfunction. In patients of the third group, alterations of myocontractility expressed a myofibrillary deficiency unable to be corrected by the multiplication and the increased exchange areas of mitochondria. PMID- 1929575 TI - [Fetus in fetu and acardiac monster: can the similar patterns of these 2 malformations be explained by a common morphogenic mechanism?]. AB - Fetus in fetu and acardiac monster are two unusual malformations (estimated incidences: 1 in 500,000 and 1 in 34,600 deliveries respectively) which present very similar morphological patterns. The authors report two cases of acardiac monster and a case of fetus in fetu which emphasize this fact. These findings suggest that a single morphogenic mechanism leads to the defects observed in these two groups of malformations. PMID- 1929576 TI - [Clear cell tumor of the lung (sugar tumour). Study of a case]. AB - A case of benign clear cell tumor ("sugar tumor") is reported. Light microscopy showed a proliferation of clear cells with a rich blood supply and endocrinoid pattern. Ultrastructurally, cells were loaded with glycogen both free and membrane-bound. The cellular origin of the benign clear cell tumor of the lung is still uncertain. PMID- 1929577 TI - [Value of the nucleolar organizers (AgNOR) in brain gliomas]. AB - The aim of the study was to evaluate the feasibility and possible contribution of silver stained nucleolar organizer regions (AgNORs) to prognostic considerations, in a series of 55 supratentorial gliomas: eight grade II astrocytomas, twelve grade III astrocytomas, thirty grade IV astrocytomas, two glioblastomas, one anaplastic oligodendroglioma, one oligodendroglioma and one ependymoma. Silver NORs (AgNORs) were demonstrated according to the method of Crocker et al. A difference between AgNOR sizes in peritumor and tumor tissue is noted. The mean NOR numbers in the tumor areas range from 0.871 to 2.677, without overlap between peritumor gliosis and glial tumors. A comparative analysis reveals significant correlations between the mean NOR number per nucleus and histological grading. This technique can play a practical role in the diagnosis and grading of tumors sampled by stereotactic biopsies: a count higher than 0.8 is highly suggestive of malignancy. In addition, the distribution of NORs may be important: intratumoral heterogeneity expresses various degrees of transcriptional activity between different glial tumors of the same grade. This technique provides information about the biological behaviour of glial tumors supplementary to that obtained from growth fraction analysis. PMID- 1929578 TI - [A classification of uterine tumors based on embryogenesis]. AB - On the basis of their results of studies of human embryos and foetuses, the authors believe that the myometrium is derived from the primitive mesenchyme, while the endometrium is derived from the coelomic mesothelium. The myometrium is the site of non-specific tumours common to all soft tissues (of other organs): leiomyoma, lipoleiomyoma, leiomyoblastoma, leiomyosarcoma; vascular tumours: angioma, haemangiopericytoma. The endometrium is the site of tumours derived either from the epithelial contingent (of glandular tubules): adenoma, adenocarcinoma; or from the epithelio-connective tissue contingents: mullerian dysplasia, carcinosarcoma (homologous mixed mesodermal tumour). The authors classify heterologous mixed mesodermal tumours in a separate group; they believe that they constitute true mixed mesodermal tumours derived from two cell clones: one of mullerian origin and the other derived from the primitive mesenchyme. PMID- 1929579 TI - Antinuclear antibodies and juvenile chronic arthritis (JCA): search for a specific autoantibody associated with JCA. PMID- 1929580 TI - Prevalence of anticardiolipin antibodies in juvenile chronic arthritis. AB - The prevalence of anticardiolipin antibodies was evaluated in 70 children with juvenile chronic arthritis (JCA), in 25 adult patients with rheumatoid arthritis, in 42 healthy children and in 40 adult controls. Thirty seven (53%) patients with JCA were positive for IgG or IgM anticardiolipin antibodies, or both, and 30 (43%) for IgG anticardiolipin antibodies. In contrast, only seven (28%) adult patients with rheumatoid arthritis presented anticardiolipin antibodies, which were of IgG class in four (16%) cases. IgG anticardiolipin antibodies were negative in all control subjects while IgM anticardiolipin antibodies were detected in two (5%) children and in four (10%) adult controls. No correlations were found in patients with JCA between the presence or titres of anticardiolipin antibodies and various clinical or laboratory variables. No patient with anticardiolipin antibodies showed any feature of the anticardiolipin syndrome. PMID- 1929581 TI - Insulin-like growth factor and growth hormone secretion in juvenile chronic arthritis. AB - Insulin-like growth factor (IGF-1) concentrations were determined in a series of 23 children with juvenile chronic arthritis in conjunction with anthropometric assessment. When standardised z scores were used significant decreases in height and weight were shown in comparison with the normal age/sex matched means. Severe growth disturbance was seen, particularly in those with prolonged disease duration, which was independent of corticosteroid treatment, indicating disease activity itself is a major factor in the growth retardation. Eight children had low IGF-1 z scores--that is, less than -2.00 from age/sex matched mean. Low IGF-1 z scores were associated with low weight z scores but not with low height z scores. Overnight growth hormone secretory profiles were determined in 10 patients, including seven with low IGF-1, and showed generally normal secretion in all but one patient, who subsequently attained normal concentrations coincident with catch up growth. Increased pulse frequency of overnight secretion was commonly seen. Low IGF-1 concentrations probably result from varying factors, particularly nutritional, but do not reflect marked endocrinological abnormalities in most patients. PMID- 1929582 TI - Reduction in IgG galactose in juvenile and adult onset rheumatoid arthritis measured by a lectin binding method and its relation to rheumatoid factor. AB - Glycosylation changes in patients with juvenile chronic and adult onset rheumatoid arthritis have been studied using a novel binding method. Both these major types of arthritis showed decreased galactosylation of serum IgG, which confirms earlier studies using a different, more complex chemical method. No significant correlation between serum IgG, IgM, and IgA rheumatoid factors and age corrected G(o) (percentage of oligosaccharide chains lacking galactose) was found. The possibility that the less glycosylated IgG is preferentially confined to circulating IgM/IgG immune complexes cannot be excluded, however. PMID- 1929583 TI - Polymyalgia rheumatica and rheumatoid arthritis of the elderly: a clinical, laboratory, and scintigraphic comparison. AB - Clinical, laboratory, and scintigraphic features of 16 patients with polymyalgia rheumatica and 23 patients matched for age presenting with classical or definite rheumatoid arthritis (American Rheumatism Association 1958 criteria) of the elderly were compared in order to define features that might distinguish between these two syndromes. The sensitivity of proposed diagnostic criteria for polymyalgia rheumatica was always higher in the group with polymyalgia rheumatica, though only significantly so for morning stiffness. A comparison of 27 different laboratory features showed few significant differences between the diseases, though correlation between laboratory variables within each of the disease groups differed, perhaps suggesting a fundamental pathogenetic difference between them. Scintigraphy of the shoulder joint proved of no value in differential diagnosis. It was concluded that polymyalgia rheumatica and rheumatoid arthritis of the elderly are probably discrete clinical entities. Bilateral upper arm tenderness, lack of positive rheumatoid factor, and a normal caeruloplasmin are the most valuable features for distinguishing polymyalgia rheumatica from rheumatoid arthritis of the elderly. PMID- 1929585 TI - Osteophytes in the osteoarthritic hand: their incidence, size, distribution, and progression. AB - Quantitative microfocal radiographic assessment of osteophytes in osteoarthritic hands showed that their number and area were greatest at joint margins, in the dominant hand, in the second and third compared with fourth and fifth phalanges, in the third phalanx, and in the second distal interphalangeal joint respectively. These sites correspond with those for the largest forces exerted in the hand: the dominant side, the finger tripod used in the precision grip, power grip, and pulp-pinch respectively. The greater osteophytosis on the trapezium of the nondominant first carpometacarpal joint was probably related to forces exerted during power grip. Osteophytes increased significantly in number and area during the 18 month study period. PMID- 1929584 TI - Comparison of clinical, radionuclide, and radiographic features of osteoarthritis of the hands. AB - Simultaneous clinical, scintigraphic, and macroradiographic assessments were carried out on 32 patients with hand osteoarthritis and the results at entry and one year reported. The presence and growth of osteophyte correlated with symptoms and a positive scan. The scan did not detect the radiographic features of juxta articular radiolucencies, subchondral sclerosis, or cartilage thinning. Osteophytes, particularly when fast growing, produce pain, a 'hot' scan, and may predict disintegration of joint architecture. PMID- 1929587 TI - Response to intradermal injection of monosodium urate crystals in Behcet's syndrome. AB - The cutaneous response to intradermal injection of monosodium urate crystals was investigated in 97 patients with Behcet's syndrome in Turkey and 14 in the United Kingdom, and in 82 healthy and 88 diseased controls. Urate crystals produced an increased erythematous response in patients compared with controls in both countries. This response was different from that of the pathergy test performed at the same time. The systemic acute phase response, studied only in Turkey, showed no differences between patients and controls. PMID- 1929586 TI - Effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol. AB - The effects of pyrazinamide, probenecid, and benzbromarone on renal excretion of oxypurinol were investigated. Pyrazinamide decreased the mean (SEM) fractional clearance of oxypurinol from 19.2 (2.1) to 8.8 (1.5). Probenecid increased the fractional clearance of oxypurinol from 14.1 (3.5) to 24.8 (4.1). Benzbromarone increased the fractional clearance of oxypurinol from 15.6 (2.3) to 33.8 (2.8). These results suggest that oxypurinol may be secreted by 'an organic acid system' and that oxypurinol is reabsorbed at a putative postsecretory site of the renal tubules. PMID- 1929590 TI - From Yugoslavia. PMID- 1929588 TI - Nocardia asteroides pneumonia complicating low dose methotrexate treatment of refractory rheumatoid arthritis. AB - Low dose methotrexate is used increasingly often in the treatment of rheumatoid arthritis. Severe complications due to toxicity of the lung or bone marrow occur infrequently. This report describes a 71 year old woman with longstanding rheumatoid arthritis who developed pleuritis, a pulmonary infiltrate, and pancytopenia during treatment with low dose methotrexate. Fatal respiratory insufficiency followed, and cultures from the lung after death showed Nocardia asteroides. PMID- 1929589 TI - Childhood eosinophilic fasciitis presenting as inflammatory polyarthritis and associated with selective IgA deficiency. AB - A 13 year old school boy presented with seronegative inflammatory polyarthritis after a flu-like illness. Four months later clinical features of eosinophilic fasciitis became apparent. After histological diagnosis treatment was started with prednisone 40 mg daily, with a good response. Routine investigations showed persistent selective IgA deficiency. PMID- 1929591 TI - Getting out and about with arthritis: or not? PMID- 1929592 TI - Juvenile chronic arthritis, chronic iridocyclitis, and reactivity to histones. PMID- 1929593 TI - Lymphoedema complicating rheumatoid arthritis. PMID- 1929594 TI - Worsening of Felty's syndrome with methotrexate. PMID- 1929595 TI - Rheumatology in Dar-es-Salaam, Tanzania. PMID- 1929596 TI - Increased serum cytidine deaminase activity in gout and articular chondrocalcinosis. PMID- 1929597 TI - The transfixational plaster cast technique. AB - Unstable fractures of the forearm and leg as well as combined fractures of the arm and forearm are often difficult to treat adequately by closed reduction and plaster fixation. In tropical countries, however, open reduction is relatively contra-indicated because of increased risk of peri-operative infection, inadequate training of medical personnel, and lack of adequate equipment. Given these conditions, the use of the transfixational plaster cast offers an alternative which is simple, inexpensive, and with few complications. The principle and technique of the transfixational plaster cast are presented. PMID- 1929599 TI - [A focus of sleeping sickness without peridomestic Glossina: Kingoyi (Congo)]. PMID- 1929598 TI - [Surveillance of the in-vivo chemosensitivity of Plasmodium falciparum to 4 aminoquinoline in the Cameroon]. PMID- 1929600 TI - [Effect of ecdysteroids on the neuroendocrine system of primates: injection of 20 hydroxyecdysone in the chimpanzee]. PMID- 1929601 TI - Epidemiological survey of 126 cases of pityriasis versicolor in the Central African Republic. PMID- 1929602 TI - [In memoriam Leonard Jan Bruce-Chwatt (6/9/1907 - 3/17/1989)]. PMID- 1929603 TI - [Epidemiology of sexually transmissible diseases in developing countries in the era of AIDS]. AB - Recent developments in the epidemiology of sexual transmitted diseases (STD) in developing countries are reviewed. STD are very frequent in the tropics, particularly in large urban areas. They put a heavy burden on public health because they affect the economically most important age groups and because their sequellae may be fatal. Pelvic inflammatory disease and its consequences, and morbidity during pregnancy and the neonatal period are among the most important causes of mother and child morbidity. STD favour sexual transmission of HIV and may therefore explain the explosive AIDS epidemics in many developing countries. Antimicrobial resistance has made treatment of gonorrhoea and chancroid more difficult and more expensive. STD and HIV infection may be responsible for up to 17% of productive years lost to disease in certain regions. Strategies to control STD should be developed and linked with the AIDS programs. Both should be integrated in the primary health care system. PMID- 1929604 TI - The right thing. PMID- 1929605 TI - Primary and recurrent Crohn's disease. Experience with 1379 patients. AB - Between 1970 and 1988, 1379 patients with Crohn's disease were treated at the University of Chicago. Of these, 639 (mean age, 32.5 years; 322 men, 317 women) required at least one surgical procedure. The most common indications for operation were failure of medical treatment (n = 215, 33%), presence of a fistula (n = 154, 24%), and bowel obstruction (n = 141, 22%). A fistula was the most common intraoperative Crohn's-related complication. In 582 patients (92%), a resection was necessary, with primary anastomosis in 416 (65%), a temporary stoma in 124 (20%), and a permanent stoma in 42 (7%). The remaining 57 patients underwent diverse procedures (stricturoplasty, bypass, and so on). Two patients (0.3%) died. Follow-up data was obtained in 95%. One hundred eighteen patients developed recurrence requiring reoperation. The recurrence rate was 20% at 5 years and 34% at 10 years. The recurrence involved a permanent stoma or a previous anastomosis in 62 patients (afferent limb in 46, efferent in 16). In the 391 patients without previous surgery for Crohn's disease, a covariate analysis was performed to determine those variables significantly associated with recurrence. Variables included demographic data, findings at operation, surgical procedures, and histopathologic characteristics. The analysis revealed that the number of sites involved was the only variable that was significantly associated with the intra-abdominal recurrence rate (p less than 0.001). The annualized risk of recurrence was 1.6% for patients with single-site involvement and 4% for those with multiple-site involvement. Perineal disease was associated with a significantly higher risk of local recurrence than any other site (p less than 0.02). A subanalysis of 236 patients with single-site involvement but no previous operation allowed us to study the influence of site on indications for surgery and type of operative procedure. Failure of medical treatment was the most common indication for all sites. In contrast the site involved influenced the procedure: resection and primary anastomosis was feasible in 88% of jejunoileal and terminal ileal cases and a temporary ileostomy was necessary in only 12%. No patients with small bowel localization required a permanent stoma. A resection with primary anastomosis was feasible in only 32% of patients with colonic disease. The remaining two thirds of patients required either a temporary or a permanent stoma. It is concluded that multisite involvement is associated with 2.5 times the rate of recurrence of single-site disease, while the presence of perineal disease has a significantly higher incidence of local recurrence.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1929607 TI - The role of prostaglandin E2 in immune suppression following injury. AB - It has been thought for some time that prostaglandin E2 (PGE2) released from activated monocytes/macrophages may contribute to the suppression of immunity seen after burns and major injury because PGE2 inhibits the activation of T lymphocytes. To clarify this issue, we studied 15 patients with total body surface area burns of 20% to 90% (mean, 48%). Peripheral blood mononuclear cells (PBMC) were obtained from these patients one to two times each week for 1 month after burn and were stimulated with the T-cell mitogen phytohemagglutinin (PHA). On 14 occasions the PBMCs from eight patients were significantly suppressed (30% or more) in their response to PHA (suppressed [sup] burn) as compared with PBMCs from normal controls. In 38 instances PBMCs from 12 patients were not significantly suppressed in PHA (nonsuppressed [nonsup] burn). Sup burn PBMCs and control PBMCs were cultured with or without the addition of the cyclooxygenase (CO) inhibitor indomethacin (Indo, 1 microgram/mL) and studied for PHA response and the production of the stimulatory cytokine interleukin-2 (IL-2). Indo partially restored the PHA response of sup burn PBMCs to normal. Sup burn PBMCs also were deficient in production of IL-2. Indo increased IL-2 production by sup burn PBMCs significantly more (160% +/- 20%, p less than 0.005) than control (57% +/- 5%) and nonsup PBMCs (67% +/- 8%). Next inhibition of the PHA response of PBMCs from 12 burn patients and 17 controls was studied by exogenous PGE2. At all time periods after burn injury, patients' PBMCs were significantly more sensitive to inhibition by PGE2 (50% inhibition at 10(-8) mol/L [molar] PGE2) than PBMCs from normal controls (50% inhibition at 10(-6) mol/L PGE2) with maximum sensitivity occurring 8 to 14 days after injury. Peripheral blood mononuclear cells from patients with more than 40% burns were significantly (p less than 0.05) more sensitive to PGE2 than those from patients with lesser burns. Interleukin-2 was added to cultures of sup burn PBMC, nonsup burn PBMC, and controls containing 10(-7) mol/L PGE2. Interleukin-2 totally reversed PGE2 inhibition of the PHA response in PBMC from both controls and burn patients. Because endotoxin leak from the gut has been implicated as a trigger for a number of the metabolic and immunologic abnormalities following injury, the authors looked for the effect of a bolus infusion of Escherichia coli endotoxin (Endo, 4 ng/kg) in seven normal healthy volunteers on the response of PBMC to PHA and on the production of PGE2 and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1929606 TI - Treatment of chronic traumatic bone wounds. Microvascular free tissue transfer: a 13-year experience in 96 patients. AB - During a 13-year period at the Massachusetts General Hospital, Boston, Massachusetts, 97 microvascular free tissue transfers have been performed for soft-tissue reconstruction in 96 patients following bone debridement for chronic traumatic bone wounds. These 96 patients comprise a continuation study of 18 original patients reported in 1982. During a 13-year follow-up period (mean, 77.1 months), 95.8% of these 96 patients have enjoyed complete wound closure with a lack of drainage after the debridement and free tissue transfer. Most of the patients (89.6%) encountered in this study are ambulatory without assist and 5.2% of patients have undergone amputation. Twenty-three per cent of patients required subsequent segmental bone defect reconstruction in the lower extremity after infection eradication. The pathophysiology of chronic traumatic bony wounds is different from that of chronic hematogenous osteomyelitis and thus a high incidence of long-term successful management can be seen through complete wound debridement and adequate soft-tissue coverage. PMID- 1929608 TI - Immunomodulatory therapy with thymopentin and indomethacin. Successful restoration of interleukin-2 synthesis in patients undergoing major surgery. AB - Prostaglandin E2 (PGE2)-mediated monocyte (M phi) suppressor activity and inadequate T-helper cell function represent the mechanistic keystones of trauma induced impairment of cell-mediated immunity (CMI). In a prospective randomized trial, the immunorestorative potential of a combined therapy with the thymomimetic substance Thymopentin (TP-5; Timunox, Cilag GMBH, Sulzbach, FRG) and the cyclooxygenase inhibitor indomethacin (Indo) in 60 patients (mean age, 63 +/- 2 years) undergoing open heart surgery was studied. Perioperative immunologic screening was carried out on days -2, 3, 1, 5, and 7 and included the in vivo delayed type hypersensitivity (DTH) skin response, phenotyping for peripheral blood mononuclear cell (PBMC)-specific and nonspecific induction of lymphoproliferative responses, in vitro interleukin-2 (IL-2) synthesis, as well as the serum concentration of D-erythro-Neopterin (NPT) and of gamma interferon (gamma-IFN). The study protocol comprised three groups (n = 20): PA (Indo 150 mg administered intravenously on days 0 to 5), PB (TP-5 administered subcutaneously on days 0, 2, 4, and Indo), and PC (control). In contrast to PC, significant immunorestoration could be demonstrated in PB, as DTH scores on day 7, as well as proliferative responses in cell cultures were not depressed after operation (p less than 0.05). Cell-surface receptor expression for the CD3+, CD4+, and IL-2 receptor-positive (IL-2R+) lymphocyte subpopulations following surgery was reduced to 75% of baseline values in PC, while in PB, receptor protection for CD4+ and IL-2R+ subpopulations (more than 15% above baseline) was observed. Interleukin-2 synthesis (average baseline value, 0.7 + 0.08 U/mL) in cell cultures of PC was massively suppressed, with lymphokine concentrations in the supernatants never more than 0.27 +/- 0.05 U/mL. In PA cultures, IL-2 synthesis was impaired as well but not as precipitously as in PC. In contrast, in PB cultures, the average IL-2 production on consecutive postoperative days was never below baseline values. This study clearly demonstrates that the combined Indo/TP 5 therapy is superior to single Indo administration and can adequately preserve and/or restore intact M phi T-cell interaction and thus appears to be a feasible approach to maintain normal host defense activity in traumatized individuals. PMID- 1929609 TI - Chronic visceral ischemia. Three decades of progress. AB - Symptomatic visceral atherosclerosis is a major surgical challenge because of its life-threatening course and the complexity of its definitive operative treatment. Evolution in the operative approach to the visceral aorta and progress in the intraoperative management of patients undergoing complex vascular reconstructions prompted a review of the authors' cumulative experience in the surgical management of chronic visceral ischemia. Among all patients undergoing visceral revascularization at the University of California, San Francisco during the past three decades, 74 patients were identified whose primary reconstruction used transaortic endarterectomy (TA TEA) (n = 48) or antegrade bypass (AB) (n = 26), the authors' preferred revascularization techniques. The two treatment groups were comparable in gender distribution, age, presenting symptoms, and physical findings, although the amount of preoperative weight loss was greater in the AB group (35.8 +/- 19.5 versus 22.4 +/- 12.0, p = 0.003). The groups were also comparable in the prevalence of atherosclerosis risk factors, symptomatic vascular disease at other sites, and previous vascular operations. However associated renal artery atherosclerosis was slightly greater in the TA TEA group (58.3% versus 23.1%, p = 0.07) when compared to the AB group. Antegrade bypass was usually performed transabdominally (88.5%), while TA TEA was approached thoracoretroperitoneally (75.0%). Celiac revascularization was almost universal in both treatment groups, but the TA TEA group underwent significantly more frequent superior mesenteric artery (SMA) revascularization (93.8% versus 46.2%, p = 0.0001) and slightly more frequent inferior mesenteric repair (18.8% versus 3.8%, p = 0.07) than the AB group. In addition the frequency of combined renal and visceral repair (25.0% versus 0.0%, p = 0.01) as well as combined aortic, renal, and visceral repair (22.9% versus 3.8%, p = 0.03) was significantly greater in the TA TEA group. The obligatory interval of renal and visceral ischemia did not differ between the two approaches. The perioperative mortality rate was 12.2% and was the same for TA TEA (14.6%) and AB (7.7%). Overall the incidence of complications was the same with either operative approach, although patients in the TA TEA group tended to have multiple complications (17.1% versus 0.0, p = 0.03) and all significant pulmonary complications occurred in this group. Two patients were lost to follow-up. The cumulative percentage of patients who remained asymptomatic following AB or TA TEA was (respectively) 95.8% and 97.3% at 1 year and 86.5% and 86.1% at 5 years. Both of these operative approaches provide durable symptom relief with acceptable operative morbidity and mortality rates.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1929610 TI - Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial. AB - The hypothesis that optimizing hemodynamics using pulmonary artery (PA) catheter (preoperative 'tune-up') would improve outcome in patients undergoing limb salvage arterial surgery was tested. Eighty-nine patients were randomized to preoperative tune-up either in the surgical intensive care unit (SICU) (group 1) or the preinduction room (group 2) or to control (group 3). The tune-up consisted of fluid loading, afterload reduction, and/or inotropic support to achieve predetermined endpoints. Patients with a PA catheter had significantly fewer adverse intraoperative events (p less than 0.05), less postoperative cardiac morbidity (p less than 0.05), and less early graft thrombosis (p less than 0.05) than the control group. The overall study mortality rate was 3.4%, with a mortality rate of 9.5% in the control group and 1.5% in the PA catheter groups. There were no differences in ICU length of stay (LOS), hospital LOS, or total hospital costs, although the percentage of cost from complications was higher in group 3 (p greater than 0.05). In this group of patients, preoperative cardiac assessment and optimization is associated with improved outcome. PMID- 1929612 TI - Second-look surgery for colorectal cancer. The second time around. AB - Eighty-six colorectal cancer patients who entered the Radioimmunoguided Surgery (RIGS) protocol study were evaluated for 2-, 3-, 4-, and 5-year survival following second-look surgical procedures. Strict preoperative evaluation criteria eliminated patients with extra-abdominal tumor involvement. A saturated potassium iodide preparation was given before the intravenous administration of the B72.3 monoclonal antibody (1 mg) radiolabeled with 2 mCi of iodine-125 by the IODOGEN method. Precordial monitoring of the biologic clearance by the handheld, gamma-detecting probe (Neoprobe 1000 instrument) was conducted at weekly intervals until the average count was less than 20 counts in 2 seconds. Once the drug cleared from the blood, surgery was performed. The mean time interval between injection and operation was 24 days, with a range of 21 to 28 days and a median of 23 days. At surgery the abdomen was explored through the traditional methods of palpation and inspection, and the surgeon committed to a planned procedure. The abdomen was then re-explored with the handheld, gamma-detecting probe and the surgeon stated another intraoperative assessment. After using both traditional and RIGS detection methods, the surgeon stated whether his or her surgical plans changed because of the additional intraoperative information provided by the RIGS system. Fifty-three patients (62%) were deemed resectable by the traditional methods of palpation and inspection, but only 40 (47%) were specified as resectable by RIGS exploration. Two-, three-, four-, and five-year survival data could be gathered for each of the three groups: RIGS resectable (n = 40), traditional nonresectable (n = 33), and RIGS nonresectable (n = 13). At 2 years 95% of the resectable, 36% of the traditional nonresectable, and 53% of RIGS nonresectable patients survived. At 3 years 83%, 7%, and 30% of these patients survived, respectively. For the resectable patients, 74% survived at 4 years and 60% at 5 years, with no survivors from either nonresectable group. Use of the RIGS system increased accurate selection of resectable patients undergoing second-look surgery for recurrent colorectal cancer. PMID- 1929611 TI - Changing trends in necrotizing enterocolitis. Experience with 302 cases in two decades. AB - Three hundred two infants with necrotizing enterocolitis (NEC) were treated from 1972 to 1990. One hundred eighteen were treated medically while 184 infants required operation. Comparisons were made between two treatment periods, 1972 to 1982 (n = 176) and 1983 to 1990 (n = 126). Infants in the more recent era were of lower birth weight (1505 +/- 853 g versus 1645 +/- 836 g), earlier gestational age (30.4 +/- 4.7 weeks versus 32.4.5 weeks; [p less than 0.01]), had symptom onset at an older age (15.7 +/- 13.9 days versus 10.0 +/- 10.8 days; [p less than 0.001]), and a lower incidence of hyaline membrane disease (p less than 0.001). Fewer patients in the 1983 to 1990 group had acidosis (p less than 0.001) and severe oliguria (p less than 0.001). Operation was performed sooner after diagnosis in the second group (2.6 versus 3.8 days; [p less than 0.001]). Survival was unaffected by sex, maternal complications, or whether infants were inborn or transferred from other facilities. Improved survival (1983 to 1990) was observed in those infants between 24 to 27 weeks gestation (p less than 0.002) and those weighing less than 1000 g (p less than 0.001). Since 1983 portal vein air (PVA) on abdominal radiographs was used as an indicator for operation. Survival in infants with PVA has improved from 29% to 64% (p less than 0.02). Despite patients being more immature and weighing less, the overall survival rate improved from 58% (1972 to 1982) to 82% (1983 to 1990) (p less than 0.001). Operative survival rate improved from 51% to 75% (p less than 0.002). Long-term survival was 75% overall and 65% for surgical infants in the 1983 to 1990 group (p less than 0.05). PMID- 1929613 TI - The role of multimodality therapy in soft-tissue sarcoma. AB - Soft-tissue sarcomas are uncommon malignancies. The development during a period of 8 years, in one institution, of a prospective data base incorporating more than 1600 patients with these tumors is described. The most common sites for occurrence are the extremities, but they can occur in any of the soft tissues of the body. Liposarcoma and leiomyosarcoma are the most common histopathologic conditions identified. Prognostic factors for both recurrence and survival include site, histopathology, size, grade, and adequacy of resection. A prospective randomized trial of the use of adjuvant radiation by the brachytherapy technique in extremity lesions has shown a decrease in local recurrence, but no impact on survival. Eligible patients not randomized to the trial show no difference in local recurrence or survival, regardless of whether they received adjuvant radiation. PMID- 1929614 TI - Transplantation of islet allografts and xenografts in totally pancreatectomized diabetic dogs using the hybrid artificial pancreas. AB - Previously the authors reported on a Hybrid Artificial Pancreas device that maintained patent vascular anastomoses in normal dogs and, when seeded with allogeneic canine islets, maintained normal fasting blood sugars (FBS) in diabetic pancreatectomized dogs. Eventual failure of these devices was believed to be related to loss of islet viability and/or insufficient islet mass. The current study evaluates the effect of increased islet mass produced by implantation of two islet-seeded devices in pancreatectomized dogs and compares the results with those from dogs that received a single device. Twelve of fifteen dogs receiving single devices showed initial function as determined by elimination or reduction of exogenous insulin requirement; four showed initial function and seven showed extended function (100 to 284 days). Excessive weight loss (more than 20%), despite normal FBS and insulin dependence, required that four animals in this latter group be killed. Devices seeded with xenogeneic islets have met with limited success. One dog that received two bovine islet seeded devices achieved function for more than 100 days; the remaining bovine seeded devices (n = 8) functioned for only 3 to 16 days. Porcine islet-seeded devices were assessed by intravenous glucose tolerance tests (IVGTT). Recipients of two devices seeded with allogeneic islets demonstrated improved IVGTT results when compared to those from pancreatectomized dogs and recipients of single devices but were abnormal when compared to intact animals. Histologic examination of device and autopsy material from all failed experiments was performed and showed no mononuclear cell infiltration of the islet chamber or vascular graft material, only a few incidence of device thrombosis, and varying degrees of islet viability as judged by morphologic and immunohistochemical evaluation. The authors believe they have demonstrated progress toward the development and clinical applicability of the Hybrid Artificial Pancreas. PMID- 1929616 TI - Diaphragm paralysis following cardiac surgery: role of phrenic nerve cold injury. AB - Diaphragm paralysis has been reported radiologically after cardiac surgery with an incidence ranging from 30% to 75% of patients. We studied 100 consecutive patients undergoing open heart operations, half of whom received ice/slush topical hypothermia (group 1) and half of whom did not (group 2). Chest radiology and diaphragm screening were performed at 1 week, 1 month, and every 6 months thereafter in all patients with an elevated diaphragm. Phrenic nerve conduction time was measured in all patients in whom there was radiological evidence of diaphragm paralysis 1 week postoperatively. The two groups were similar in terms of age and sex. Aortic cross-clamp time was less in group 1 (61.5 +/- 15.6 minutes) compared with group II (74.4 +/- 20.8 minutes), although this difference was not significant. Significant differences, however, were found for radiological evidence of partial left lower lobe collapse (82% in group 1 versus 32% in group 2; p less than 0.01) and for radiological evidence of diaphragm paralysis (32% in group 1 versus 2% in group 2; p less than 0.001) within the first postoperative week. Unilateral diaphragm paralysis developed in 16 group 1 patients (15 left sided, 1 right sided) compared with only 1 patient in group 2. In these 16 group 1 patients, diaphragm paralysis was still present in 12 (75%) at 1 month and in 5 (31.3%) at 1 year postoperatively. There were no significant differences between the two groups in terms of postoperative arrhythmias, myocardial infarction, or mortality. Phrenic nerve conduction time was found to be a sensitive indicator of phrenic nerve cold injury and recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929615 TI - Not all neonatal hearts are equally protected from ischemic damage during hypothermia. AB - Despite hypothermia, pediatric cardiac surgeons continue to experience difficulties in providing adequate myocardial protection in newborns. This study examines the effects of deep hypothermia on neonatal heart tolerance to ischemia by measuring metabolic responses and the time to onset of ischemic contracture, or "stone heart." After control right ventricular biopsy specimens were obtained, hearts of newborn pigs (n = 36) were excised and placed in temperature-regulated baths: 37.5 degrees +/- 0.5 degrees C (n = 9), 19.0 degrees +/- 0.5 degrees C (n = 14), and 12.0 degrees +/- 0.5 degrees C (n = 13). With a compliant balloon in the left ventricle to measure pressure, time to onset of ischemic contracture (greater than 2-mm Hg rise) was recorded, and sequential biopsies were done. Data indicated hypothermia significantly (p less than 0.001) prolonged time to onset of ischemic contracture from 29.5 +/- 1.7 minutes (mean +/- standard error of the mean) at normothermia to 150.0 +/- 6.4 minutes at 19 degrees C and to 283.8 +/- 46.4 minutes at 12 degrees C. Lactate buildup at 30 minutes of ischemia was significantly reduced by 70% with hypothermia. Decline in adenosine triphosphate level was significantly reduced by 50% (19 degrees C) and 75% (12 degrees C) with hypothermia. More importantly, a subgroup of hearts in each hypothermia group (n = 5 per group) was identified by 38% to 48% lower adenosine triphosphate stores before ischemia compared with the group means.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929617 TI - Warm heart surgery: experience with long cross-clamp times. AB - Although hypothermic cardioplegic arrest prolongs the period of ischemic arrest by reducing oxygen demands, it leaves the heart dependent solely on anaerobic metabolism for its energy demands and exposes it to the detrimental effects of hypothermia. Consequently, myocardial protection is compromised, and safe aortic occlusion time is limited to 120 minutes. As electromechanical arrest accounts for 90% of myocardial oxygen consumption, we hypothesized that an ideal state of the heart might be chemically arrested and perfused with warm blood, ie, aerobic arrest. We applied this approach to myocardial protection in 308 consecutive procedures. To assess the adequacy of this method, we reviewed the results in a group of 22 patients in whom the aortic cross-clamp time was, of necessity, greater than or equal to 3 hours (mean time, 204 minutes; range, 180 to 393 minutes). Nineteen of the patients represented a high operative risk with grade 3 or 4 left ventricular function and New York Heart Association class III or IV. All hearts resumed spontaneous normal sinus rhythm without defibrillation, and 21 patients were easily weaned from bypass within minutes of removal of the aortic cross-clamp without inotropic or intraaortic balloon pump support. Mortality was 4.5%, low-output syndrome occurred in 4.5%, and there were no perioperative myocardial infarctions. Our results suggest that warm aerobic arrest is safe and effective in prolonged high-risk procedures, virtually eliminating the period of ischemia, limiting the period and injury of reperfusion, and abolishing the detrimental effects of hypothermia. PMID- 1929618 TI - Right atrial versus aortic root perfusion with blood cardioplegia. AB - The efficacy of coronary sinus cardioplegia administered into the right atrium has not been fully defined. Thirty-two consecutive patients undergoing elective myocardial revascularization were prospectively assigned to receive cold blood cardioplegia exclusively into the aortic root (15 patients) or the right atrium (17 patients). The two groups were similar with respect to age, ventricular function, severity of coronary disease, cross-clamp time, and mean infusate volume and temperature. Completeness of revascularization was greater in the aortic root cardioplegia group (p less than 0.007). The mean septal temperature and time to achieve electromechanical arrest was greater in the right atrial cardioplegia group (p less than 0.05). The right ventricular temperature and the release of myocardial isoenzyme were similar in both groups. Left and right ventricular stroke work index was preserved equally in both cohorts. Volume loading studies performed immediately after termination of bypass suggested better left ventricular function in the aortic root cardioplegia group. Myocardial performance with a loading challenge assessed late postoperatively was superior in the right atrial cardioplegia group (p less than 0.05). There were no differences between the groups with respect to clinical outcome. The data suggest that right atrial cardioplegia (1) possesses clinical safety equal to aortic root cardioplegia, (2) possesses inferior ventricular septal cooling, and (3) yields adequate preservation of both the right and left ventricles. We conclude that right atrial cardioplegia possesses no apparent advantage over aortic root delivery in the setting of elective myocardial revascularization. PMID- 1929619 TI - The limits of cardiac preservation with University of Wisconsin solution. AB - Previous studies from this institution have suggested that University of Wisconsin solution is preferred for prolonged cardiac storage and preserves high energy phosphates better than other storage fluids. University of Wisconsin solution contains adenosine (5 mmol/L), which may maintain the concentration of myocardial adenine nucleotides. Cultures of human adult myocytes were grown from left ventricular biopsy specimens obtained from patients undergoing coronary bypass procedures. Cells (seven to nine dishes per group) were rinsed of culture medium and stored at 0 degrees C in University of Wisconsin solution. Cells were analyzed for adenine nucleotide content after 1, 6, 12, and 24 hours of storage by high-performance liquid chromatography (units = nmol/microgram DNA) and compared with control samples (0 hour). Adenosine concentration increased from 0.03 +/- 0.02 (mean +/- standard deviation) to 1.77 +/- 1.03 by 1 hour (p less than 0.0001, analysis of variance) and remained increased thereafter. Adenosine was largely degraded to inosine (0 hours, 0.03 +/- 0.03; 6 hours, 0.88 +/- 0.56; p less than 0.001) and hypoxanthine (0 hours, 0.01 +/- 0.01; 6 hours, 0.15 +/- 0.09; p = 0.004). Measured levels of xanthine and uric acid were extremely low at all time intervals. Adenosine triphosphate levels were maintained at 1 hour (0 hours, 0.64 +/- 0.38; 1 hour, 0.67 +/- 0.45) but declined thereafter (6 hours, 0.21 +/- 0.21; 12 hours, 0.11 +/- 0.09; 24 hours, 0.04 +/- 0.03; p less than 0.0001). Levels of adenosine diphosphate (p = 0.007) and adenosine monophosphate (p less than 0.05) decreased to approximately 25% of original values by 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929621 TI - Ultrasonic lung suction: where to next? PMID- 1929620 TI - Effects of platelet-activating factor antagonist CV-3988 in preservation of heart and lung for transplantation. AB - The preservation of heart and lung for transplantation remains a major concern in extended ischemic intervals. This experiment evaluated the effect of high molecular weight deferoxamine and a platelet-activating factor antagonist (CV 3988) in ischemic reperfused tissue. Heart-lung transplantation was performed in a swine model after 4 hours 45 minutes of ischemia. Animals were divided into three groups. Group A was a control without pharmacological intervention. In group B, high molecular weight deferoxamine, 50 mg/kg, was used, and in group C, platelet-activating factor antagonist CV-3988, 10 mg/kg, was used. The results of functional variables (cardiac index, stroke index, lung water, oxygen and carbon dioxide tensions, alveolar-arterial gradient, and alveolar-arterial ratio) demonstrated superior heart and lung function for groups B and C compared with the control group. These alterations of heart and lung function were significantly less (p less than 0.001) in group C, in which the platelet activating factor antagonist (CV-3988) was used. The study revealed that formation of hydroxyl radicals and platelet-activating factor play an important role in the pathogenesis of ischemia reperfusion injury. Prevention of hydroxyl radical formation with high molecular weight deferoxamine and inactivation of platelet-activating factor with CV-3988 reduce the ischemia-reperfusion injury significantly. PMID- 1929622 TI - Nomenclatura obscura: subaortic obstruction in double-inlet left ventricle and related lesions. PMID- 1929623 TI - Multiple reoperative coronary artery bypass grafting. AB - Initial reoperative coronary artery bypass grafting is being performed commonly, and an increasing number of patients are being referred for subsequent reoperative coronary artery bypass grafting. From January 1980 through June 1990, 53 patients (52 male, 1 female) underwent a third or fourth coronary artery bypass operation and were retrospectively reviewed. This represented 0.3% (53/17,102) of the coronary artery bypass procedures done during that time period. The mean age was 59 +/- 8 years. The number of grafts placed ranged from one to four with an average of 2.6 per patient. Internal mammary artery grafts were used in 30 patients (57%). The mean left ventricular ejection fraction was 0.52 +/- 0.13. Intraaortic balloon pump support was necessary in 10 patients postoperatively. There were no intraoperative deaths, although 4 patients died in the postoperative hospitalization period. Perioperative myocardial infarctions were diagnosed in 6 patients, 13 patients had perioperative dysrhythmias, and 2 patients sustained a stroke. Superficial wound infections occurred in 5 patients. Late follow-up in 49 patients revealed that 2 other patients have since died, and no further myocardial infarctions have been reported in the survivors. Postoperative 3-year survival is 85%, whereas 3-year myocardial infarction-free survival is 70%. Although there is increased risk of operative complications and early death after multiple reoperative coronary artery bypass grafting, both in hospital and long-term results suggest that it is an appropriate therapeutic strategy. PMID- 1929624 TI - Fibrin sealant improves surgical results of type A acute aortic dissections. AB - From January 1984 to July 1990, 63 patients were operated on for type A acute aortic dissection. Forty-two patients (aged 22 to 80 years) had isolated replacement of the ascending aorta with the following techniques: group 1 (n = 10) had replacement of the ascending aorta with an intraluminal sutureless graft, group 2 (n = 14) had a Dacron prosthesis sutured to the aorta, and in group 3 (n = 18) the proximal and distal aortic stumps were glued together and reinforced at the suture sites with fibrin sealant before implantation of the Dacron prosthesis. There were no significant differences between the three groups with respect to age, sex, or preoperative clinical and anatomical data. Three (30%) intraoperative deaths occurred in group 1, 4 (29%) in group 2, and none in group 3. Cross-clamp and extracorporeal circulation time were significantly lower in group 1 when compared with groups 2 and 3. Perioperative blood loss during the first 24 hours was significantly lower in group 3 (372 +/- 155 mL) when compared with group 1 (755 +/- 210 mL; p less than 0.05) or group 2 (1,055 +/- 370 mL; p less than 0.01). Total hospital mortality was 7 (70%) in group 1, 6 (43%) in group 2, and 1 (5.5%) in group 3. All patients were reviewed: one late death occurred in group 2 and none in the other groups. All survivors were in good clinical condition. In conclusion, intraluminal sutureless grafts allowed shorter cross-clamp and extracorporeal circulation time but did not improve surgical results for treatment of type A acute aortic dissections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929625 TI - Inotropic stimulation and oxygen consumption in a canine model of dilated cardiomyopathy. AB - Inotropic support for the dilated, failing ventricle results in complex hemodynamic changes affecting preload, afterload, contractility, and heart rate, each of which affects myocardial oxygen consumption. Appreciation of a hierarchy of hemodynamic determinants of myocardial oxygen consumption may be helpful to the clinician trying to balance oxygen demands and hemodynamic performance. We tested the hypothesis that epinephrine alters the hierarchy of hemodynamic determinants of myocardial oxygen consumption in a canine model of dilated cardiomyopathy created by rapid ventricular pacing. Dogs (n = 10) were instrumented to record left ventricular pressure and dimension, and a modified right heart bypass preparation was used to control left ventricular workload. Coronary sinus effluent was quantitatively collected and analyzed for oxygen content and used to calculate myocardial oxygen consumption. Epinephrine administration significantly increased myocardial oxygen consumption in the empty, beating heart; however, when the relationships of multiple determinants of left ventricular work and load were compared before and after epinephrine administration, no oxygen wasting effect was observed. Using multivariate linear regression analysis, a hierarchy of hemodynamic determinants of myocardial oxygen consumption was created. In the untreated heart, stroke work and cardiac output were the primary hemodynamic determinants of oxygen consumption; epinephrine significantly altered the determinants such that wall stress became the dominant hemodynamic determinant of myocardial oxygen consumption. Focused manipulation of wall stress in the treated, failing heart may limit the potentially deleterious effects of inotropic stimulation in this setting. PMID- 1929626 TI - Management of acquired nonmalignant tracheoesophageal fistula. AB - Acquired, nonmalignant tracheoesophageal fistula is an uncommon and difficult problem to manage. The most common cause is a complication of endotracheal or tracheostomy tubes. Most are diagnosed while patients still require mechanical ventilation. We use a conservative approach until patients are weaned from ventilation. A tracheostomy tube is placed so that the balloon rests below the fistula, if possible, to prevent contamination of the tracheobronchial tree. A gastrostomy tube is placed for drainage and a separate jejunostomy tube for nutrition. Single-stage repair is done after the patient is weaned from mechanical ventilation. Esophageal diversion is rarely required. We have performed 41 operations on 38 patients. Simple division and closure of the fistula was done in 9 patients and tracheal resection and reconstruction in the remainder. The esophageal defect was closed in two layers and a viable strap muscle interposed between the two suture lines. There were four deaths (10.9%). There were three recurrent fistulas and one delayed tracheal stenosis. All were successfully managed. Of the 34 surviving patients, 33 aliment themselves orally and 32 breathe without the need for a tracheal appliance. PMID- 1929627 TI - Angioscopic evaluation of intravascular morphology after coronary endarterectomy. AB - Coronary endarterectomy in diffuse coronary disease is attended by an increased incidence of perioperative myocardial infarction and vein graft occlusion, which have been partially attributed to the presence of occlusive or thrombogenic intraluminal flaps in the main vessel or its smaller branches. To define the nature and incidence of these features we studied 15 endarterectomized right coronary arteries in 15 patients (12 men, 3 women; age, 55 +/- 7 years [mean +/- standard deviation]) undergoing a coronary operation for multivessel disease. After endarterectomy and distal graft anastomosis, angioscopy was performed using a 1.8-mm Olympus angioscope during graft perfusion with crystalloid solution. The endarterectomy cores were 66 +/- 30 mm in length with 11 major bifurcations and two trifurcations providing 30 major endpoints. At 22 of 30 major endpoints the distal end of the core was smooth and tapered. There were 17 minor side-branch endpoints. Angioscopy revealed the presence of wispish intraluminal fronds and medial bruising in all (100%) arteries. Twenty-nine of the 30 intraluminal endpoints could be visualized. Major intraluminal flaps were seen at the eight nontapered endpoints and six of the 21 smooth tapered endpoints that were visualized. Fifteen minor side branches could be identified angioscopically: a flap was seen at only one side-branch origin. The average examination time was 3.2 +/- 1.1 minutes (7.7% +/- 2.7% of cross-clamp time), and examination required 200 to 250 mL of perfusate. This technique enables immediate and accurate postinterventional assessment of intravascular morphology with minimal prolongation of ischemic time and has shown that small side branches are not compromised by endarterectomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929628 TI - Multiple primary lung carcinomas: prognosis and treatment. AB - From 1955 to 1990, 111 patients have been treated for multiple primary lung carcinomas. Criteria for diagnosis were: (1) different histology (n = 44); or (2) same histology, but disease-free interval at least 2 years (n = 39), origin from carcinoma in situ (n = 19), or metachronous disease in different lobe (n = 9) with no cancer in common lymphatics or extrapulmonary metastasis at the time of diagnosis. The second cancer was synchronous in 33 patients (30%) and metachronous in 78 (70%). Metachronous disease developed at a median interval of 48 months. Five-year survival for patients with metachronous and synchronous disease from the time of initial diagnosis of cancer was 70% and 44%, and 10-year survival was 42% and 23%, respectively. Survival after the development of a metachronous lesion was 23% at 5 years. Survival from the time of initial diagnosis was significantly better for metachronous versus synchronous, late (24 month disease-free interval) versus early metachronous disease, and adenocarcinoma versus epidermoid carcinoma. The first cancer was completely resected in 103 patients (93%), but complete resection of a metachronous tumor was possible in only 54 patients (69%). Complete resection of second primary cancers resulted in significantly (p less than 0.0001) prolonged 5-year survival compared with incomplete resection (38% versus 9%). Excluding patients requiring pneumonectomy, initial resection limited subsequent resection in only 7 patients (9%) with metachronous disease. We conclude that patients surviving treatment of primary lung cancers require lifelong screening for multiple primary lung carcinoma, and complete resection is recommended whenever possible. PMID- 1929629 TI - Repair of truncus arteriosus in infancy. AB - Improvements in myocardial protection, surgical technique, and postoperative care have decreased operative mortality for neonatal repair of truncus arteriosus. Primary repair of truncus arteriosus in infancy without prior pulmonary artery banding is currently the preferred approach. During the period from 1982 to December 1990, 32 patients under the age of 12 months underwent surgical correction of truncus arteriosus at UCLA. The average age was 3.5 months (range, 12 days to 12 months). Three patients had interrupted aortic arch. Early mortality for the entire group was 15.6% (5/32); for those older than 1 month early mortality was 7% (2/28). In the past 4 years, early mortality has decreased to 8.3% (2/24); both of these patients had interrupted aortic arch. Excluding patients with interrupted aortic arch, there were no early deaths in the last 22 patients (1986 to 1990). Late mortality overall was 7.4% (2/27). In a mean follow up of 73 months (range, 40 to 110 months), 71% (5/7) of the survivors with Dacron porcine-valved conduits required conduit replacement secondary to obstruction. In a mean follow-up of 36 months (range, 1 to 89 months), only 14% (3/21) of the patients with homografts required replacement secondary to obstruction. PMID- 1929630 TI - Ultrasonic surgical aspirator for lung resection. AB - The ultrasonic surgical aspirator was originally developed for neurosurgical procedures and hepatic resections. Ultrasonic vibration at the tip of the instrument results in lysis of the parenchymal cells, leaving more resistant fibrous tissue such as blood vessels and bronchi intact and, thus, minimizing blood loss. We have studied the feasibility of applying the ultrasonic surgical aspirator for segmental and subsegmental lung resection for primary and metastatic neoplasms of the lung. Over the past 5 years, 27 patients underwent segmental or limited lung resection using the ultrasonic surgical aspirator. Except for prolonged air leak in 6 patients postoperatively, no other serious morbidity was noted. We observed several advantages: (1) the ultrasonic surgical aspirator dissects out the pulmonary vessels and bronchi, allowing the surgeon to perform segmental and subsegmental resections with minimal blood loss, (2) it permits lung-sparing operation for centrally located tumors that would otherwise have required lobectomy, and (3) it allows direct visualization of lung parenchyma during dissection, thus assuring grossly adequate margins. PMID- 1929631 TI - Thyroid hormone changes after cardiovascular surgery and clinical implications. AB - Alterations in serum concentrations of total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) frequently occur in patients with nonthyroidal illnesses. These changes correlate with the severity of the illness and the prognosis. In this study, 44 patients undergoing a cardiovascular operation had significant declines in serum TT3 and TT4 levels during cardiopulmonary bypass and thereafter. Serum TT3 and TT4 concentrations reached their nadir at 30 minutes after the start of cardiopulmonary bypass with values (mean +/- standard error of the mean) of 0.77 +/- 0.12 nmol/L (50.4 +/- 7.6 ng/dL) and 68.2 +/- 10.2 nmol/L (5.30 +/- 0.79 micrograms/dL), respectively. The mean serum concentrations of TSH and TT4 returned to preoperative levels by the sixth day after operation, whereas TT3 levels remained low throughout the study period. The patients whose recovery was uneventful had higher serum TT3, TT4, and TSH levels than those who had complications or died. The trend toward recovery was initiated by a sharp increase in the serum TSH level and increases in serum TT3 and TT4 concentrations on the fourth day after operation. Patients with complications either did not show these changes or had only a transient increase in TT3 and TT4 levels. All of the patients had a normal serum free T4 level before anesthesia. Those with an uneventful recovery had a higher serum free T4 level on the sixth day after operation than those with complications. Two patients in the latter group had serum free T4 levels less than normal at that time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929632 TI - Heart rate-right ventricular stroke volume relation with myocardial revascularization. AB - Whether increasing pacing frequency in cardiac surgical patients effectively improves right ventricular cardiac index depends on the interrelationships between heart rate, stroke volume index, and end-diastolic volume index. If an inverse relation exists between heart rate and right ventricular volume then the decrease in right ventricular ejection fraction described after bypass may be due, in part, to changes in heart rate. We evaluated the effects of pacing at 80, 95, and 110 beats/min using a thermodilution volumetric catheter in 16 patients undergoing myocardial revascularization. End-diastolic volume index, stroke volume index, and stroke work index were significantly greater after bypass than before bypass, whereas right ventricular ejection fraction remained constant. Before and after bypass, sequentially increasing pacing frequency from 80 to 110 beats/min decreased stroke volume index by 28% to 35% (p less than 0.001), end diastolic volume index by 12% to 14% (p less than 0.001), and right ventricular ejection fraction by 18% to 24% (p less than 0.001). Right ventricular performance, assessed by comparing the stroke volume index to end-diastolic volume index and stroke work index to end-diastolic volume index relations generated during pacing, was not altered by bypass. We conclude that sequentially increasing heart rate from 80 to 110 beats/min fails to improve stroke volume index and consequently cardiac index before or after cardiac operations. Intraoperatively, in patients with normal left ventricular function, increasing pacing frequency decreases right ventricular ejection fraction due to simultaneous reductions in stroke volume index and end-diastolic volume index. PMID- 1929633 TI - Simultaneous revascularization for critical coronary and peripheral vascular ischemia. AB - Patients with coronary artery disease can exhibit substantial vascular involvement, and patients with vascular disease have a high incidence of coronary disease. Simultaneous coronary artery bypass grafting and treatment of vascular disease was performed in 32 patients with strong indications for surgical treatment of coronary artery disease and critical peripheral vascular ischemia operated on from 1980 until 1990. Overall hospital mortality was 3.1%; 1 patient died of myocardial infarction 2 days after urgent combined revascularization because of unstable angina pectoris and subacute occlusion of the aortoiliac bifurcation. Early mortality was 0% in patients undergoing elective operations. Eight-year actuarial survival was 87.5%. Combined procedures can be performed with acceptable risk and with encouraging long-term results in this special group of patients; they may improve prognosis in patients with diffuse atherosclerosis. PMID- 1929634 TI - Assessment of retrograde cardioplegia distribution using contrast echocardiography. AB - Retrograde cardioplegia has gained popularity in coronary and noncoronary cardiac operations. We have used contrast echocardiography in the open-chest canine model to compare the distribution of cardioplegia delivered antegrade in the aortic root versus retrograde through the coronary sinus, and to determine the effect of coronary occlusion on that delivery. With no coronary occlusion, antegrade cardioplegia was distributed to the entire left ventricle and septum whereas retrograde cardioplegia was distributed to the left ventricular free wall but had inconsistent delivery to the septum. Acute occlusion of the left circumflex coronary artery resulted in 57.06% +/- 9.52% of the left ventricle not being perfused by antegrade cardioplegia and occlusion of both the left circumflex and anterior descending coronary arteries caused a 65.46% +/- 18.5% reduction in perfusion by antegrade cardioplegia. Acute coronary occlusion had no effect on retrograde cardioplegia distribution. We conclude that retrograde cardioplegia is less homogeneous than antegrade cardioplegia in the intact coronary circulation but that retrograde cardioplegia preserves cardioplegia distal to acutely occluded coronary arteries. Furthermore, contrast echocardiography is a useful method of assessing myocardial perfusion and may have useful clinical applications. PMID- 1929635 TI - Comparative study of the hydrodynamic function of the CarboMedics valve. AB - The hydrodynamic function of each size of the CarboMedics valve was assessed in a pulsatile flow simulator. The mean pressure difference with respect to forward flow, regurgitant volumes, and total energy loss across each valve were analyzed. The results for the 23-mm aortic and 29-mm mitral CarboMedics valves were compared with those for the St. Jude Medical and Bjork-Shiley Monostrut valves. Results showed good hydrodynamic function for each CarboMedics valve, although the pressure difference and total energy loss across the 19-mm aortic valve was high. The hydrodynamic function of the CarboMedics valve was comparable with that of the St. Jude Medical valve. Both valves showed similar leakage volumes, which were significantly larger than that for the Bjork-Shiley Monostrut valve. On account of this the total energy loss in the Bjork-Shiley valve was significantly less than that for the bileaflet valves in the aortic position. Concern remains for the continuing presence of high closed-valve regurgitation in the bileaflet valves. PMID- 1929636 TI - Chest wall reconstruction with degradable processed sheep dermal collagen in dogs. AB - Chest wall defects resulting from oncological operations often require prosthetic repair. The objectives of prosthetic repair are to provide a cosmetically acceptable substitute, prevent paradoxical chest wall movement, and protect vital organs. Of the many materials that have been used in these repairs, none have proved to be ideal. The aim of our study was to investigate the application of a biodegradable material--processed sheep dermal collagen--as a chest wall prosthesis. A full-thickness chest wall defect of 10 x 10 cm was created in 12 dogs; 10 had repair with a processed sheep dermal collagen prosthesis and 2, the controls, with polypropylene mesh. In this study, the biomaterial fulfilled its function as a chest wall prosthesis at 24 weeks' follow-up. No respiratory problems were seen, the chest wall remained stable with minimal and decreasing respiratory paradoxical movement, and the processed sheep dermal collagen slowly degraded and was replaced by the host collagen. Processed sheep dermal collagen offers long-term advantages because it is degradable. Late complications from a nonabsorbable prosthesis, ie, infection or disintegration of the material possibly causing extrusion or fistula formation, are avoided. PMID- 1929637 TI - Intraabdominal complications after cardiopulmonary bypass. AB - Thirty-three intraabdominal complications occurred in 27 patients over a 16-year period in 4,629 patients who underwent cardiopulmonary bypass (0.58% incidence). The mortality was 14.8% for the intraabdominal complication group compared with 3.4% for the control group of patients (p less than 0.01). The most common complication was gastrointestinal hemorrhage (n = 20), of which esophagitis (n = 6) was the most common cause. However, patients with duodenal ulcer (n = 4) had the highest mortality; 2 patients who underwent truncal vagotomy and pyloroplasty subsequently died. Two further patients underwent operation for perforated anterior duodenal ulcers without further morbidity. Cholecystitis developed in 5 patients and acute pancreatitis in 4; all were managed nonoperatively with no mortality. Multisystem organ failure developed in 2 patients, of whom 1 died. There was a significant correlation between intraabdominal complications and prolonged bypass time. The mean bypass time was 96.7 +/- 28.6 minutes for the patients with gastrointestinal complications, compared with 81.7 +/- 48.4 minutes for the whole group (p less than 0.01). No correlation was demonstrated for type of operation undergone or the age of the patient. In the last 5 years, 2,145 patients underwent cardiopulmonary bypass, of whom 562 received pulsatile and 1,583 nonpulsatile flow. The incidence of intraabdominal complications was 0.18% (n = 1) in the pulsatile group compared with 0.63% (n = 10) for the nonpulsatile group (p = 0.14). Intraabdominal complications, although of low incidence, carry a significantly high mortality, and the clinician must be alert in the postoperative period to institute early therapy. PMID- 1929638 TI - Prevention of ischemia-reperfusion injury by the allergy drug lodoxamide tromethamine. AB - Lodoxamide tromethamine, an orphan antiallergy drug, inhibits degranulation of mast cells that reside in the myocardium and inhibits xanthine oxidase located in myocytes and predominantly in the vascular endothelium. The hypothesis evaluated was that lodoxamide tromethamine would attenuate oxygen free radical damage. Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing 0, 1, 10, 100, or 1,000 mumol/L lodoxamide tromethamine at 37 degrees and 24 degrees C with ischemic times of 22 and 93 minutes, respectively. These ischemic intervals yielded 50% survival and 50% return of function in untreated hearts. Lodoxamide treatment alone at the onset of reperfusion was also studied. Performance end points were aortic flow, pressure, and coronary flow. Biochemical analyses included serotonin collected from coronary effluent as a marker of mast cell degranulation, uric acid for xanthine oxidase inhibition, myocardial adenosine triphosphate, and carbonyl group concentrations. Performance data demonstrated that lodoxamide was beneficial in a log-linear dose response when given continuously at both temperatures. Percent of preischemic values for untreated and maximal responses at 1,000 mumol/L of lodoxamide were as follows: a mortality of 50% in nontreated hearts versus 0%; aortic flow, 47% to 94% (37 degrees C), 46% to 86% (24 degrees C); cardiac output, 60% to 98% (37 degrees C), 58% to 97% (24 degrees C); adenosine triphosphate, 59% to 90% (37 degrees C), 48% to 65% (24 degrees C). Serotonin was undetectable from any hearts. Uric acid concentrations and carbonyl group content did not change with increasing dose. Lodoxamide demonstrated no benefit when given only during reperfusion, suggesting injury occurred at times other than reperfusion. PMID- 1929639 TI - Mitral valve replacement: techniques to eliminate myocardial rupture and prevent valvular disruption. AB - Twenty fresh canine hearts were used to compare the peak left ventricular pressures required to disrupt prosthetic mitral valves sutured in place with horizontal mattress sutures using either subannular or supraannular placed pledgets. Separate groups were developed to determine the effect of leaving the whole mitral valve apparatus or only the posterior leaflet apparatus intact and what effect, if any, each had on the ventricular pressure required to disrupt the implanted prosthetic mitral valve. Group 1 consisted of 10 hearts with the entire mitral apparatus left in place (5 valves implanted with supraannular pledgets and 5 with subannular pledgets). Group 2 consisted of 10 hearts with only the posterior leaflet apparatus left in place (5 valves implanted with supraannular pledgets and 5 with subannular pledgets). A 29-mm Medtronic mitral valve was secured in the mitral position with a fixed number of ten pledgeted sutures in each annulus. The aorta was cannulated and normal saline solution infused into the left ventricle until end-point rupture occurred. The peak pressure and mechanism of any disruption were then noted. No specimen exhibited subannular myocardial rupture or left atrial wall dissection. Similar protection was provided by leaving the posterior leaflet only or the entire mitral valve. In each case peak left ventricular pressure resulted in only paravalvular leaking around the limited number of sutures as the end point. In each of these four groups the peak left ventricular pressures required for end-point rupture were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929640 TI - Traumatic sinus of Valsalva fistula. AB - Two rare cases of nonpenetrating trauma-induced fistula from the right sinus of Valsalva to the right heart chambers are reported. Both were diagnosed preoperatively and operated on successfully. A transverse tear was found in the right sinus of Valsalva, just below the right coronary ostium, in both patients. The ragged inlet and a rough fistula tract were noted during operation. The tears were closed with direct sutures or with a Dacron patch. Coronary artery bypass grafting was needed in 1 patient. The results of operation were excellent. PMID- 1929641 TI - Bronchial neurofibrosarcoma. AB - A 56-year-old woman was seen with the clinical features of collapse of the right lower lobe. Intrabronchial extension of a tumor was demonstrated endoscopically. Sleeve bilobectomy was performed, and a diagnosis of bronchial neurofibrosarcoma was confirmed by light and electron microscopic and immunohistochemical studies. PMID- 1929642 TI - Anatomically corrected malposition of the great arteries. AB - We report the case of an infant with anatomically corrected malposition of the great arteries in solitus [S, L, D], associated with ventricular septal defect, patent ductus arteriosus, and right juxtaposition of the atrial appendages. The aortic pole was posterior to the tricuspid mitral line and the conus was bilateral. Successful surgical repair was undertaken by the Senning procedure with closure of ventricular septal defect and division of the ductus. Postoperative cardiac angiography demonstrated no hemodynamic obstruction or residual shunt. PMID- 1929643 TI - Constrictive pericarditis from Nocardia asteroides infection. AB - Human nocardiosis usually involves the respiratory tract or the skin but may disseminate to virtually any organ. It occurs in immunocompromised hosts as well as individuals with no apparent predisposition. Involvement of the pericardium is uncommon, having been reported infrequently in the past, but mandates surgical management. This report describes the course of a patient with chronic constrictive pericarditis from nocardia successfully treated with pericardiectomy and appropriate antibiotic therapy. PMID- 1929644 TI - Repair of mycotic aneurysm of the innominate artery with homograft tissue. AB - The case of a 46-year-old drug addict who underwent repair of a mycotic aneurysm of the innominate artery with a 12-mm homograft is presented. The homograft was obtained from the descending thoracic position in a young child. Replacement of infected arteries with various artificial grafts risks recurrent infection and anastomotic disruption. The use of a homograft conduit in this case was successful in restoring the appropriate blood flow without infection. We suggest that the homograft conduit can be used in other areas with similar results. PMID- 1929646 TI - Primary Aspergillus osteomyelitis of the sternum. AB - We report 2 cases of primary sternal osteomyelitis caused by Aspergillus; previously reported cases have been complications of sternotomy. Both patients were healthy young men with recent intravenous drug abuse. No other focus or predisposing factors were found. Both were treated with partial sternectomy and chondrectomy; 1 received long-term amphotericin B therapy. Both are doing well 2 1/2 years after operation. Drug usage, acquired immunodeficiency syndrome, and medical immunosuppression may lead to other cases. PMID- 1929645 TI - Patent foramen ovale: a cause of hypoxemia in patients on left ventricular support. AB - We describe 2 patients who experienced right-to-left shunting during support with a left ventricular assist device as a result of patent foramen ovale. In the first patient, the patent foramen ovale was not found until autopsy. In the second patient, fluctuations in continuous mixed venous oxygen saturations caused us to suspect a patent foramen ovale, which was confirmed with transesophageal contrast echocardiography. We promptly repaired the defect and this patient survived. When patients on assist devices experience unexplained arterial hypoxemia, a patent foramen ovale should be considered. If a patent foramen ovale is found, surgical correction should be done early. PMID- 1929647 TI - Cardiac transplantation in a patient with a single ventricle and transposition of the great vessels. AB - The technical details of orthotopic cardiac transplantation in a 17-year-old man with a single ventricle and transposition of the great vessels are described. Special considerations in the evaluation and management of patients with complex congenital heart disease who are to undergo cardiac transplantation are delineated. PMID- 1929648 TI - Cardiac retractor for coronary bypass operations. AB - The Thompson retractor, used mainly for abdominal procedures, has been used to retract the heart and facilitate exposure for the performance of inferior wall or posterolateral wall coronary anastomoses. It has been found to be very effective and can replace a second assistant to retract the heart or avoid other cumbersome methods of cardiac retraction. PMID- 1929649 TI - Simplified placement of retrograde cardioplegic catheter. AB - A method is described for rapid placement of a retrograde cardioplegia catheter at a precise location in the coronary sinus. Palpation of the posterior cardiac surface is not required, thus facilitating use of retrograde coronary sinus cardioplegia in cardiac reoperations. PMID- 1929650 TI - Tuberculosis, the Adirondacks, and coming of age for thoracic surgery. AB - "The Captain of all these men of death," wrote John Bunyan in 1680, "that came against him to take him away, was the Consumption, for it was that that brought him down to the grave." Until the twentieth century tuberculosis, or the Consumption, was the foremost cause of death among adults. It had not been recognized as a specific infectious process until 1882. The sanatorium movement for segregation and treatment of tuberculous patients originated in the late nineteenth century. Locations in the mountains were thought to be especially favorable, for the sake of fresh air, sunshine, and the aromas of pine and spruce. Long before the epidemic of lung cancer, or the possibilities of correction for cardiac disease, development of thoracic surgery was closely intertwined with the history of the sanatoriums. All of them had disappeared, however, soon after the middle of the twentieth century. PMID- 1929651 TI - Cardiac tumors: clinical experience and surgical results in 74 patients. AB - A series of 75 cardiac tumors in 74 patients were operated on at La Pitie Hospital between 1972 and 1989. There were 73 primary and 2 metastatic tumors. Among the benign neoplasms, 58 were myxomas; seven of the nine malignant tumors were primary heart tumors. The mean age of the patients was 48 years (range, 9 to 75 years); 46 patients were female and 28 male. Fifty-seven percent of the patients had congestive heart failure, 13% had chest pain, 17% had neurological symptoms, and only 1 patient was totally asymptomatic. The cardiac tumors were incidental findings in 3 patients. Complete resection was carried out in 66 benign lesions and only four of the malignant tumors. All patients survived operation, although 4 died in the early postoperative period. Long-term results were excellent in patients with benign lesions, and no recurrences were found. In patients with malignant tumors, surgical procedures were only palliative and aimed at prolonging life; hence, prognosis remained unchanged. PMID- 1929652 TI - Spasm in free arterial grafts. PMID- 1929654 TI - Poststernotomy infections. PMID- 1929653 TI - Tricuspid and mitral valve repair. PMID- 1929655 TI - Effect of pH shifts induced by oxygenating crystalloid cardioplegic solutions. AB - Oxygenation of a bicarbonate-containing crystalloid cardioplegic solution alters the partial pressure of both oxygen (O2) and carbon dioxide (CO2). Therefore, oxygenating St. Thomas' Hospital II plus glucose (11 mmol/L) cardioplegic solution with 95% O2 + 5% CO2 induces a pH shift to 7.0 (10 degrees C) as opposed to pH 9.3 with 100% O2. In an isolated working rat heart model, we show that pH 7.0 (10 degrees C) improves mechanical postischemic recovery in the absence or presence of O2. However, in the absence of O2, pH 7.0 appears to inhibit glycolysis and diminish the stability of cellular membranes. The provision of O2 independently improved mechanical recovery and at pH 7.0, improved the preservation of the sarcolemma. Increasing the O2 content by including a perfluorocarbon (FC-43) in the oxygenated St. Thomas' plus glucose cardioplegia is not additionally beneficial. St. Thomas' Hospital plus glucose cardioplegic solution should be oxygenated, but with 95% O2 + 5% CO2 and not 100% O2. PMID- 1929656 TI - Protection of ischemic heart from reperfusion injury by myo-inositol hexaphosphate, a natural antioxidant. AB - Myo-inositol hexaphosphate (phytic acid), a highly charged antioxidant, has been found to chelate metal ions such as iron and calcium and to scavenge hydroxyl radicals, .OH. This study examined the efficacy of this antioxidant and redox agent in attenuating myocardial reperfusion injury. Sprague-Dawley rats were injected intravenously with three different doses of phytic acid (group 1, saline solution only, control; group 2, 1.5 mg/100 g; group 3, 7.5 mg/100 g; group 4, 15 mg/100 g) 30 minutes before excision of hearts. Isolated hearts were prepared by the Langendorff technique. Global ischemia was induced for 30 minutes, followed by 30 minutes of reperfusion. As expected, in group 1, reperfusion was associated with enhanced creatine kinase release, reduced coronary flow, poor recovery of ventricular function as evidenced by reduced left ventricular developed pressure and the first derivative of left ventricular pressure, and increased lipid peroxidation. Groups 3 and 4, but not group 2, demonstrated myocardial protection as evidenced by reduced creatine kinase release, improved left ventricular function and coronary flow, and decreased lipid peroxidation compared with the control group. These results suggest that potential use of this antioxidant in salvaging the heart from ischemic and reperfusion injury. PMID- 1929657 TI - Continuous versus intermittent cardioplegia in the presence of a coronary occlusion. AB - Coronary artery occlusions can alter the distribution of cardioplegia and result in ischemic damage. This study was undertaken to determine whether continuous antegrade cardioplegia delivery would result in colder temperatures and provide better washout of acid metabolites than is possible with intermittent antegrade cardioplegia when coronary occlusions are present. Twenty pigs were placed on cardiopulmonary bypass and underwent 2 hours of ischemic arrest with occlusion of the middle left anterior descending coronary artery followed by 1 hour of reperfusion without occlusion of that artery. Ten pigs received intermittent (every 20 minutes) antegrade potassium crystalloid cardioplegia (4 degrees C), and 10 others had the same solution given continuously (30 mL/min). Cardioplegia distribution was assessed by continuous monitoring of myocardial pH (Khuri pH probe) and temperature in the region beyond the occlusion of the left anterior descending coronary artery. Both cardioplegic techniques resulted in tissue acidosis (continuous group, 6.69 +/- 0.08, versus intermittent group, 6.73 +/- 0.07; not significant). Average temperature in the left anterior descending coronary artery during arrest was also similar in both groups (continuous group, 18.3 degrees +/- 0.5 degrees C, versus intermittent group, 18.2 degrees +/- 0.5 degrees C). Because of these metabolic changes, both cardioplegic techniques resulted in abnormal wall motion in the anteroseptal region using two-dimensional echocardiography, but the scores were not significantly different (continuous group, 1.5 +/- 0.3, versus intermittent group, 1.6 +/- 0.4; 4 = normal to 0 = dyskinesia).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929658 TI - Captopril, an ACE inhibitor, for optimizing reperfusion after acute myocardial infarction. AB - Captopril is an angiotensin-converting enzyme inhibitor that has been reported to be effective in salvaging post-ischemic reperfused myocardium by its ability to function as a free radical-scavenging agent. A study was performed in the isolated porcine-heart model evaluating the influence of pretreatment with captopril on salvage of myocardium after an induced myocardial infarction. Measurement was carried out of regional and global myocardial function, myocardial high-energy phosphate levels, creatine kinase release, malonaldehyde formation, and 6-keto-prostaglandin F1 alpha generation. In an in vitro preparation, the influence of captopril for scavenging various free radicals was evaluated. A dose-response curve was carried out using this free radical generating system and differing levels of captopril. Results of the study demonstrate that pretreatment with captopril at a 45-mumol/L level reduced reperfusion injury in the pig heart model. This was manifested by improved cardiac performance, a reduction in creatine kinase release, and reduced malonaldehyde generation. In vitro evaluation of captopril and its free radical scavenging ability indicated that it is a weak scavenger of superoxide anions (O2 ) but behaves as a potent scavenger of hydroxyl radicals (-OH) as well as hypohalite radicals (OCl-). Based on the influence of captopril in reducing lipid peroxidation (decreased malonaldehyde formation) and its documented ability to scavenge -OH as well as OCl-, it is suggested that myocardial preservation in a postinfarction model is due primarily to its free radical-scavenging activity, primarily of the potent free radicals -OH and OCl-. PMID- 1929659 TI - Efficacy of myocardial protection with hypothermic blood cardioplegia depends on oxygen. AB - The role of oxygen (O2) in blood cardioplegia (BCP) remains controversial. On the one hand, O2 reduces ischemic injury between BCP infusions by maintaining energy production through oxidative pathways. On the other hand, O2 carried by blood may not be released to the tissue at 4 degrees C or potentially provides substrate for deleterious O2 radical species. This study tests the hypothesis that O2 is a critical component in myocardial protection afforded by BCP. In 17 anesthetized dogs, left ventricular performance was measured by left ventricular end-systolic pressure-volume relations using the position of the end-systolic pressure-volume relation quantitated by the left ventricular midrange volume intercept at 100 mm Hg (V100) to describe performance. After 30 minutes of global normothermic ischemia, hearts were protected with multidose 4 degrees C BCP for 1 hour of arrest. Oxygen content in BCP was adjusted to 1.1 +/- 0.2 vol% (n = 7; desaturated BCP group), 4.3 +/- 0.5 vol% (n = 5; intermediate oxygenated BCP group), or 10.2 +/- 0.6 vol% (n = 5; saturated BCP group) using a membrane oxygenator interposed in the BCP circuit and aerated with an appropriate mixture of O2, nitrogen, and carbon dioxide. After 1 hour of 37 degrees C reperfusion, 3 of the 7 dogs in the desaturated BCP group failed to generate sufficient cardiac output to discontinue bypass. In the remaining 4 dogs, severe left ventricular depression caused a rightward shift in V100 from 17 +/- 4 to 47 +/- 9 mL (p = 0.02). With intermediate BCP, all hearts were weaned from bypass with marginal left ventricular depression (V100, 20 +/- 5 versus 46 +/- 16 mL; p = 0.10). In contrast, hearts protected with saturated BCP showed no significant increase in V100 (13 +/- 4 versus 24 +/- 13 mL; p = 0.23). We conclude that O2 in BCP is critical to its myocardial protective properties. PMID- 1929660 TI - Myocardial oxygen consumption after fibrillation in the nonhypertrophied porcine ventricle. AB - Prior studies of nonischemic ventricular fibrillation have identified variable bioenergetic defects that depend on the prevailing frequency of electrical activation, coronary perfusion pressure, and left ventricular wall tension. In hearts in the adequately perfused, vented, and nondistended state the myocardial oxygen consumption of ventricular fibrillation may not be significantly different than that of the empty, beating heart. Thus, the present study investigated both global normothermic ischemic and nonischemic prolonged ventricular fibrillation effects on cardiac energetics when quantitated in the same heart under constant and defined nonworking conditions. At constant heart rate and perfusion pressure, preload recruitable stroke work was preserved in the nonischemic group but depressed to 41% of control postischemically (p = 0.018). Under control conditions, no significant differences in myocardial oxygen consumption between the various nonworking cardiac states were detected. However, postischemic empty, beating hearts and empty, fibrillating hearts both extracted (31%) and consumed (26%) less oxygen (p less than 0.03 each) without concomitant coronary hyperemia. Prolonged nonischemic ventricular fibrillation increased coronary blood flow 158% (p less than 0.03) without augmenting myocardial oxygen consumption. These data contrast with the previously reported increased oxygen demand of ventricular fibrillation and suggest that postischemic fibrillation is not bioenergetically deleterious in the nonhypertrophied heart under controlled working conditions. PMID- 1929661 TI - Relation of myocardial protection to cardioplegic solution pH: modulation by calcium and magnesium. AB - The relationship between myocardial preservation and cardioplegic solution pH was assessed in isolated, perfused rat hearts. A base solution without calcium or magnesium and the same solution containing 0.2 mmol/L ionized calcium or 16 mmol/L magnesium or both ions were studied at several values of pH between 6.8 and 8.7. Hearts were arrested at 8 degrees C by multidose infusions of these bicarbonate-buffered solutions bubbled with oxygen and a varying percentage of carbon dioxide to control pH. Diastolic tone (left ventricular balloon) and adenosine triphosphate (ATP) depletion during arrest both increased as the cardioplegic solution became more alkaline. Calcium increased these effects of pH. Magnesium weakened the effect of pH on diastolic tone, maintained ATP at all pH levels, and inhibited the effects of calcium on the relationships of pH to diastolic tone and ATP. When data from all solutions were considered together, ATP depletion was shown to be linearly related to diastolic tone. Calcium depressed functional recovery (left ventricular developed pressure during reperfusion expressed as a percentage of its prearrest value) at all pH levels. With the other solutions, recovery was similar and best within a broad and relatively alkaline pH range. With the solution containing calcium and magnesium, at pH levels of 8.28 +/- 0.02, 7.87 +/- 0.03, 7.58 +/- 0.02, 7.41 +/- 0.01, 7.06 +/- 0.02, and 6.80 +/- 0.01, recovery at 5 minutes of reperfusion was 101.4% +/- 3.7%, 102.9% +/- 2.8%, 107.3% +/- 3.7%, 102.8% +/- 2.9%, 91.8% +/- 3.6%, and 94.3% +/- 3.5%, respectively. This effect of alkalinity was short-lived. Extreme alkalinity of the base, acalcemic solution produced the calcium paradox, as reported previously. Good preservation of ATP by the most acid solutions did not predict good functional recovery. Magnesium increased the persistence of frequent extrasystoles during early reperfusion, but the effect was attenuated by calcium. The data support the inclusion of magnesium in cardioplegic solutions, particularly when they contain calcium, show that cardioplegic solution pH can have major effects on the arrested heart, and suggest that a relatively alkaline pH may modestly benefit functional recovery. PMID- 1929662 TI - Fatty acids suppress recovery of heart function after hypothermic perfusion. AB - Working rat hearts were perfused for 15 minutes at 37 degrees C before switching to a Langendorff perfusion (60 mm Hg aortic pressure) at 10 degrees C for 40 minutes of hypothermic arrest. Ventricular function was allowed to recover for 15 minutes at 37 degrees C by reestablishing the prehypothermic conditions. The perfusate was Krebs-Henseleit bicarbonate buffer containing 3% bovine serum albumin and either glucose (11 mmol/L) or glucose (11 mmol/L) plus palmitate (1.2 mmol/L) and gassed with 95% O2 and 5% CO2. In hearts receiving glucose alone as substrate, coronary flow was maintained constant during the 40 minutes of hypothermic arrest and returned to prehypothermic rates with rewarming. Ventricular function, as estimated by peak systolic pressure and heart rate, recovered to the prehypothermic level. When palmitate was added, coronary flow decreased continuously throughout the hypothermic perfusion (22% decrease by 40 minutes), and ventricular pressure development was lower throughout the rewarming perfusion. Tissue levels of adenosine triphosphate and creatine phosphate were well maintained and long-chain acyl coenzyme A and acyl carnitine decreased during hypothermia regardless of the substrate provided. With rewarming, tissue levels of adenosine triphosphate and creatine phosphate decreased in those hearts receiving palmitate. Omission of fatty acid either during hypothermia or during the first 5 minutes of rewarming improved recovery of function. Addition of oxfenicine to inhibit fatty acid oxidation, or inhibition of Ca2+ overload by verapamil and low perfusate Ca2+, prevented the effects of palmitate on ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929663 TI - Effect of cardioplegic preservation on intracellular calcium transients. AB - Intracellular Ca2+ ([Ca2+]i) plays a pivotal role in the regulation of cardiac function. We investigated the effect of cardioplegic preservation on [Ca2+]i transients in the isolated and perfused guinea pig heart loaded with a fluorescent Ca2+ indicator (fura-2). The measurements of [Ca2+]i transients and isovolumetric left ventricular pressure revealed that [Ca2+]i transients and mechanical responses to [Ca2+]i were markedly altered during 15 minutes of normothermic global ischemia and after reperfusion. First, [Ca2+]i transients remained during ischemia without generation of active force of contraction. Such a manifestation of depressed sensitivity of the myofilaments to Ca2+ persisted for the first 5 minutes after reperfusion. Second, the amplitude of [Ca2+]i was diminished during ischemia and reperfusion. Third, diastolic [Ca2+]i was increased during ischemia and especially at the onset of reperfusion. Bolus infusion of cold St. Thomas' Hospital solution abolished [Ca2+]i transients and left ventricular pressure development at an end-diastolic level. Moreover, improved recovery of left ventricular function during reperfusion afforded by the hypothermic cardioplegia was intimately related to its ability to modulate impaired [Ca2+]i transients and mechanical responses to [Ca2+]i; improvement of systolic left ventricular function appears to be produced by restoration of Ca2+ sensitivity of the myofilaments and the amplitude of [Ca2+]i transients, whereas better diastolic compliance of the left ventricle is ascribed to significantly lower diastolic [Ca2+]i. These results may provide new insight into the mechanism of cardioplegic preservation on the basis of [Ca2+]i transients. PMID- 1929664 TI - Isolated, perfused neonatal rat heart preparation for studies of calcium and functional stability. AB - We describe an isolated, perfused preparation for neonatal rat hearts to assess the relationship between extracellular calcium and (1) cardiac function and (2) contractile stability over 2 hours of perfusion. Neonatal (3 to 5 days old) rat hearts (n = 6 per group) were perfused for 30 minutes (Langendorff) with oxygenated buffer (37 degrees C) containing 1.4 mmol/L calcium (control period) and 90 minutes with buffer containing 0.5, 0.8, 1.0, 1.2, 1.4, 1.8, or 2.5 mmol/L calcium. Upon changing from 1.4 mumol/L to either a higher or low calcium concentration there were no significant changes in left ventricular developed pressure, heart rate, or coronary flow. However, left ventricular developed pressure progressively deteriorated in a time-dependent and calcium-dependent manner. Thus, after 90 minutes, developed pressure fell to 18% +/- 2%, 27% +/- 3%, 41% +/- 5%, 47% +/- 8%, 55% +/- 10%, 64% +/- 5% and 76% +/- 4% of its initial value with 0.5, 0.8, 1.0, 1.2, 1.4, 1.8, and 2.5 mmol/L calcium. In conclusion, in studies with the neonatal rat heart, extracellular calcium concentrations in the range of 1.8 to 2.5 mmol/L are recommended. PMID- 1929665 TI - Calcium content of St. Thomas' II cardioplegic solution damages ischemic immature myocardium. AB - Clinical application of hypothermic pharmacologic cardioplegia in pediatric cardiac surgery is less than satisfactory, despite its well known benefits in adults. Protection of the ischemic immature rabbit heart with hypothermia alone is better than with hypothermic St. Thomas' II cardioplegic solution. Control of cellular calcium is a critical component of cardioplegic protection. We determined whether the existing calcium content of St. Thomas' II solution (1.2 mmol/L) is responsible for suboptimal protection of the ischemic immature rabbit heart. Modified hypothermic St. Thomas' II solutions (calcium content, 0 to 2.4 mmol/L) were compared with hypothermic Krebs bicarbonate buffer in protecting ischemic immature (7- to 10-day-old) hearts. Hearts (n = 6 per group) underwent aerobic "working" perfusion with Krebs buffer, and cardiac function was measured. The hearts were then arrested with a 3-minute infusion of either cold (14 degrees C) Krebs buffer (1.8 mmol calcium/L) as hypothermia alone or cold St. Thomas' II solution before 6 hours of hypothermic (14 degrees C) global ischemia. Hearts were reperfused, and postischemic enzyme leakage and recovery of function were measured. A bell-shaped dose-response profile for calcium was observed for recovery of aortic flow but not for creatine kinase leakage, with improved protection at lower calcium concentrations. Optimal myocardial protection occurred at a calcium content of 0.3 mmol/L, which was better than with hypothermia alone and standard St. Thomas' II solution. We conclude that the existing calcium content of St. Thomas' II solution is responsible, in part, for its damaging effect on the ischemic immature rabbit heart. PMID- 1929666 TI - [Ischemic cardiopathy in women]. PMID- 1929667 TI - [Heart valves (anatomo-pathologic study of 1139 cases]. AB - We review the pathological specimens sent to the Pathology Department from January 1983 to June 1988 that belonged to 7567 patients. For this study we have selected specimens from 1139 patients (15.05% of the total), who were submitted to valvular replacement surgery. We analyzed 1037 "native" valves and 186 prosthesis. Rheumatic fever was confirmed in 68% of "native" valves. The remaining 32% includes a group in which this etiology was not confirmed by histology in spite of the clinical diagnosis. The leading cause of biological prosthesis replacement was dysfunction caused by calcification and fibrosis, and for mechanical prosthesis it was thrombosis. Included in this study are 747 patients who received 836 heterologous valves of bovine pericardium, fabricated at the "Instituto Nacional de Cardiologia (INC)". The price of imported mechanical prosthesis is superior to the price of the prosthesis manufactured at INC. The difference varies between 1400% and 4000% depending on mechanical prosthesis type. The survival rate of the receiving patients of the INC implants was 82.2%, and the dysfunction rate of these prosthesis was 3.38% for the period studied, four and a half years. PMID- 1929668 TI - [Exercise test in patients with permanent pacemakers]. AB - From June 1988 to June 1990 we studied fifty patients who had implantation of a pacemaker. (31 females and 19 males). All of them underwent stress test with Bruce's protocol. Patients were divided in two groups; pacemaker-independent (PI) and pacemaker-dependent (PD). Over 50% of the patients inhibited the pacemaker with their own rhythm, most of them had sinus dysfunction. Complete A-V block was predominant in PD. The group of PI achieved more mets and had more oxygen consumption. Blood pressure response was similar in both groups. PMID- 1929669 TI - [Positive exercise test in hypertensive patients correlated with coronary angiography]. AB - With the purpose of evaluate the state of the coronary arteries in hypertensive patients with positive exercise test, 82 patients were selected, 50 male and 32 female with mean age of 56.9 +/- 13.2 years. Angiography was normal in 25 patients thirteen patients had a single coronary arteries narrow of less than 50% and 44 cases with significant coronary arteries lesions of more than 50%. The parameters obtained in the exercise test are not significant for statistic purposes. Systolic hypertension or flat response was more frequent in the group with advanced coronary lesions with a predicted positive value in coronary obstructions of 66 and 75%. We conclude that 70% of hypertensive patients have obstructive coronary lesions of some degree. PMID- 1929670 TI - [Acute myocardial infarction in young adults. Analysis of risk factors and coronary angiography]. AB - Eighty patients aged under forty, survivors of an episode of acute myocardial infarction (AMI), were studied by means of angiography. Thirty five had anterior wall infarction, 26 diaphragmatic wall, 9 lateral side and 10 non Q AMI. Tobacco addiction (92% vs 71.9%) and hyperlipemia (34% vs 18.8% were higher (p less than 0.01) that in the total AMI population. They presented an average ejection fraction of 0.56 +/- 0.15 and only in three patients was under 0.30. One, 2 and 3 vessels disease respectively of 43%, 22% and 16%, similar to another series published. A 19% of patients with normal angiography coronaries was seen significantly higher (p less than 0.01) than the observed in AMI in older patients. In conclusion in spite of the good prognosis of this group of patients, is necessary to insist in primary preventive campaigns, mainly against tobacco addiction and hyperlipemia, in order to reduce the frequency of AMI in young people. PMID- 1929671 TI - [Partial pericardial tamponade immediately after cardiac surgery]. AB - Partial pericardial tamponade is a critical situation frequently misdiagnosed. We describe five patients with this entity during an urgent surgical reintervention performed few hours after the initial one. We found clots compressing cardiac cavities in all, usually in the right atrium. In one of them we found also a clot compressing the left atrium. None of the patients studied had the classical clinical features of cardiac tamponade (Kussmaul's sign: pulsus paradoxus) and we found no difference in blood pressure, quantity of bleeding or pulmonary capillary pressure, considering the reinterventional moment in comparison to the values taken immediately after the initial surgery and the ones registered during the surgical reintervention. There was significative increase in the central venous pressure value, decreased urine output and drop in the cardiac index. Based on this observation, we believe it is possible to have a presumptive diagnosis of partial pericardial tamponade by bidimensional echocardiographic studies just before the surgical reintervention. PMID- 1929673 TI - [Postoperative course of prosthetic valve replacement]. AB - In order to know the post-operative outcome of patients with valvular replacement due to prosthetic dysfunction, we reviewed the clinical charts of 94 patients operated at the Instituto Nacional de Cardiologia "Ignacio Chavez" between January 1986 and December 1988. Eighty four cases were replaced by the first time the remaining 10 by a second time. Diagnosis of prosthetic dysfunction was made by clinical, radiological, echocardiographic and haemodynamic parameters. The most frequent causes of dysfunction were the rupture of prosthetic leaflets, stenosis with calcific deposition and paravalvular leaks. The global mortality rate was 19.15%, higher than the native valve replacement group. The most important predictors of surgical mortality were: 1) poor ventricular function (functional classes III and IV), 2) aortic clamping period, 3) the need of a second prosthetic replacement and 4) the time of prosthetic dysfunction. Thus, we conclude that it is of great importance the early recognition of prosthetic valve dysfunction. The need of special surgical procedures in these cases should be evaluated in order to reduce morbidity and mortality. PMID- 1929672 TI - [Surgical treatment of supraventricular tachycardias (Wolff Parkinson White and Occult Kent). Experience at the "Ignacio Chavez" National Institute of cardiology]. AB - We report our initial experience in the surgical section of the accessory pathway in thirteen patients: eight patients with Wolff Parkinson White syndrome and five with accessory pathway functioning only in direction ventricle to atrium (Kent concealed), with recurrent episodes of paroxysmal supraventricular tachycardia with no response to medical treatment. Three of these patients had episodes of auricular fibrillation with interval RR lower than 250 msec and one patient presented syncope. A total of fifteen accessory pathways were sectioned: 7 left lateral, 5 left posterior, one left posterolateral, one right lateral, and another one right anteroseptal. In the same procedure two patients had correction of another heart malformation: one with patent ductus arteriosus and another with and another with atrial septal defect. All patients had successful outcome, one of them needed a second surgery for persistent accessory pathway. We had two post operatory complications: one mediastinitis and one patient with ectopic auricular tachycardia. PMID- 1929674 TI - [Hemodynamic and angiocardiographic assessment of thoracopagus twins for surgical separation purposes]. AB - The rate of conjoined twins is 1 in 50,000 births. These patients usually have a common pericardial sac (90%) and conjoined hearts (75%). In case of shared heart there is a communication by a vascular channel between both atria and ventricles. If there is not ventricular communication, surgical separation is possible. We describe such a case in whom in spite that interventricular connections were present; surgical separation was decided because of the critical conditions of twin A in an effort to preserve the survival of twin B. PMID- 1929675 TI - [Multiple cause of death in cardio- and cerebrovascular diseases]. AB - In order to validate mortality studies, we described the role of hypertension at the time of death of people who died during April and May 1985. This analysis take into account all the causes listed in death certificates and not only the underlying cause. A proportional mortality design was used to evaluate the relationship of hypertension, cerebrovascular and cardiovascular disease. The number of deaths associated to hypertension was larger by multiple cause than by underlying cause. The odds ratio for hypertension and ischemic heart disease was 4.1 adjusted by age and sex, and 21.1 for cerebrovascular disease. PMID- 1929676 TI - [Changes in lipoprotein metabolism. III. Treatment]. PMID- 1929677 TI - Influence of low-intensity warfarin treatment on patients' perceptions of quality of life. PMID- 1929678 TI - Atrial fibrillation and embolic stroke. PMID- 1929679 TI - Atherogenic effects of anabolic steroids on serum lipid levels. A literature review. AB - This article reviews the current body of literature linking anabolic steroids to atherogenic alterations in serum lipid levels. Anabolic steroids cause marked high-density lipoprotein2 levels [corrected] depression (weighted average, 52%) and severe depression of high-density lipoprotein b levels (weighted average, 78%) while raising low-density lipoprotein levels an average of 36%. The mechanism of these lipid changes, their time course in relation to anabolic steroid use, and their dependency on route of anabolic steroid administration are discussed. Interpretation of the observed lipid level changes in light of the epidemiologic data linking lipids to coronary heart disease risk is used to estimate the lipid-based increase in coronary heart disease risk due to anabolic steroid use. PMID- 1929680 TI - Axillary and subclavian venous thrombosis. Prognosis and treatment. AB - To clarify the prognosis of axillary and subclavian deep venous thrombosis and to determine which clinical factors influence its sequelae, we systematically reviewed the English-language literature published on this subject since 1950. Seventy-one case reports and 17 case series describing a total of 329 patients met our inclusion criteria for detailed review. There were major deficiencies in the quality, as well as quantity, of the available clinical data: few patients were enrolled at axillary and subclavian deep venous thrombosis inception, and outcome assessments were susceptible to bias and based on insensitive diagnostic tests. Posttreatment symptoms were reported in 34% of cases, pulmonary embolism in 9.4% (one half documented by lung scan or angiography), and death in 1.2% (three of four deaths due to pulmonary emboli). These complications occurred regardless of etiologic category (spontaneous, catheter related, or miscellaneous). Thrombolytic agents and surgery, in addition to anticoagulation, were often used to treat axillary and subclavian deep venous thrombosis, but there were no controlled trials to support any one approach. Until such trials are performed, therapy should be based on the anticoagulation regimens proved to be effective for deep venous thrombosis of the lower extremity. In selected patients, thrombolytic therapy and surgery may have important roles. PMID- 1929681 TI - The impact of long-term warfarin therapy on quality of life. Evidence from a randomized trial. Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. AB - To determine the effect of long-term warfarin sodium therapy on quality of life, we surveyed 333 patients participating in a randomized, controlled trial of warfarin for the prevention of stroke in nonrheumatic atrial fibrillation. No significant differences between warfarin-treated and control patients were found on well-validated measures of functional status, well-being, and health perceptions. For example, the summary score for health perceptions was 68.8 in the warfarin-treated vs 66.6 in the control group (scale of 0 to 100; 95% confidence intervals for the difference, -1.6 to 6.0). In contrast, patients taking warfarin who had a bleeding episode had a significant decrease in health perceptions (-11.9; 95% confidence interval, -4.1 to -19.6). Warfarin therapy is not usually associated with a significant decrease in perceived health, unless a bleeding episode has occurred. Negative effects of warfarin treatment on health perceptions may be balanced by confidence in its protective effects. PMID- 1929682 TI - Physicians' attitudes toward oral anticoagulants and antiplatelet agents for stroke prevention in elderly patients with atrial fibrillation. AB - The use of oral anticoagulants and antiplatelet agents for the prevention of strokes in elderly patients with atrial fibrillation is controversial. Recent studies suggest that warfarin and aspirin can be safe and effective in selected patients. To determine attitudes toward this subject, we sent a questionnaire to 480 attending physicians at two major university-affiliated medical centers. Among the 251 responses (52.3%), 46 respondents (18.3%) used warfarin in atrial fibrillation of any cause, 175 (69.7%) used it in atrial fibrillation with transient ischemic attacks, 161 (64.1%) used it in patients with cerebrovascular accidents, and 196 (78.0%) used it in patients with mitral valve disease. One hundred twenty-nine (51.4%) believed that the risk of hemorrhage associated with warfarin outweighs the benefit, 61 (24.3%) were not convinced that warfarin prevents strokes in atrial fibrillation, and 42 (16.7%) believed it was difficult to monitor prothrombin time in the elderly because of poor compliance. Aspirin was used by 91 physicians (36.2%) in atrial fibrillation of any cause, 161 (64.1%) in patients with transient ischemic attacks, 140 (55.7%) in patients with cerebrovascular accidents, and 48 (19.1%) when patients were in sinus rhythm. We concluded that physicians are still hesitant to use oral anticoagulants and antiplatelet agents for the prevention of strokes in their elderly patients with atrial fibrillation. These agents are used most frequently after an ischemic episode (transient ischemic attack or cerebrovascular accident) has occurred or in patients with mitral valve disease. PMID- 1929684 TI - Should nonsteroidal anti-inflammatory drugs be stopped before elective surgery? AB - PURPOSE: --To determine if perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) might be associated with increased postoperative morbidity. PATIENTS AND METHODS: --Records from 165 patients undergoing total hip arthroplasty from 1984 to 1987 were reviewed. Patients taking NSAIDs at hospital admission were compared with those who were not. RESULTS: --Patients taking NSAIDs had more postoperative bleeding complications (gastrointestinal tract bleeding and/or hypotension) than did patients not taking those agents. Complications were more frequent in patients using NSAIDs with half-lives longer than 6 hours. CONCLUSION: --Patients undergoing elective surgery should stop taking NSAIDs in time to allow elimination of the drug; those patients who need to take these agents perioperatively should use drugs with short half-lives. PMID- 1929683 TI - Treatment of hypertension in the elderly. III. Response of isolated systolic hypertension to various doses of hydrochlorothiazide: results of a Department of Veterans Affairs cooperative study. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. AB - In a double-blind randomized study, we evaluated the effects of 25 mg vs 50 mg of hydrochlorothiazide in 51 elderly patients (aged 68.9 +/- 7.0 years) with isolated systolic hypertension (blood pressure, 160 to 239 mm Hg systolic and less than 90 mm Hg diastolic). Dose levels could be increased to twice daily to control blood pressure. The reductions in blood pressure (25.4/6.8 mm Hg and 28.9/7.4 mm Hg) and proportion of patients in whom blood pressure was controlled (78% and 89%) were similar in the lower- and higher-dose groups during the titration phase. However, serum potassium level was reduced more in the higher dosage (0.57 mmol/L) than the lower-dosage (0.17 mmol/L) group. There were no significant changes in blood pressure during a 24-week maintenance phase. No patient required withdrawal from the study because of adverse effects, and cognitive-behavioral function was well preserved. We conclude that hydrochlorothiazide is effective and well tolerated in older patients with isolated systolic hypertension, many of whom may be effectively treated with 25 mg of hydrochlorothiazide once daily. PMID- 1929685 TI - Oral contraceptive use may protect against low bone mass. Henry Ford Hospital Osteoporosis Cooperative Research Group. AB - This cross-sectional retrospective epidemiologic study investigated risk factors for low bone mineral density (BMD) in a group of 2297 women, 76% of whom were postmenopausal. Reproductive information, history of oral contraceptive use, BMD measurements, and other data were available from women presenting to 12 osteoporosis screening centers in 1986 and 1987. Each woman was classified into a BMD category based on the range of BMD measurements at her respective center. Menopause, increasing age and years since menopause, and decreasing body mass index were associated with low BMD. A history of oral contraceptive use was protective against low BMD (odds ratio = 0.35, 95% confidence interval = 0.23 to 0.53). Multivariate analyses confirmed this result and further demonstrated that increasing duration of use was protective. These data suggest that prior use of oral contraceptive agents is associated with higher levels of BMD and that the degree of protection from lower BMD is related to duration of exposure. PMID- 1929686 TI - The effects of estrone (Ogen) on spinal bone density of postmenopausal women. AB - The effects of cyclical treatment with estrone sulfate (0.3, 0.625, or 1.25 mg), plus calcium carbonate, on spinal trabecular bone density were compared with placebo in 120 postmenopausal women in this 2-year, multicenter, double-blind study. While the placebo and 0.3-mg treatment groups lost bone density (-3.6% and -5.1%), the 0.625- and 1.25-mg treatment groups experienced no significant change from baseline at 24 months (-0.8% and +0.7%). The 1.25-mg treatment group was significantly different from the placebo group at 12, 18, and 24 months. Although the 0.625-mg treatment group was significantly different from the placebo group only at 18 months, the data suggest that 0.625 and 1.25 mg of estrone sulfate had different effects than placebo and 0.3 mg of estrone sulfate and, given with supplemental calcium, are effective doses for the prevention of spinal bone loss. PMID- 1929687 TI - Long-term use of nicotine vs placebo gum. AB - Medical patients (n = 315) who wished to quit smoking were randomly assigned in a double-blind manner to receive either nicotine or placebo gum. Subjects were advised to stop gum use by 4 months. Among abstinent smokers, 46% of those receiving nicotine gum and 17% of those receiving placebo gum used the gum beyond the recommended 4-month period. By 10 months after cessation 17% of quitters receiving nicotine gum and 6% receiving placebo gum were still using gum. Gradual reduction of nicotine gum did not result in withdrawal and cessation of nicotine gum did not increase the probability of relapse to smoking or weight gain. We conclude that use of nicotine gum is due, in part, to the effects of nicotine; however, long-term use is uncommon. PMID- 1929689 TI - The utilization of pneumococcal polysaccharide vaccine among elderly Medicare beneficiaries, 1985 through 1988. AB - Since July 1981, Medicare has paid for the administration of pneumococcal vaccine without regard to the deductible limit and without copayment. Claims submitted to Medicare for reimbursement for the 4-year period from 1985 through 1988 for a 5% sample of elderly Medicare beneficiaries enrolled in part B who were not members of health maintenance organizations were analyzed. Vaccine was administered to an estimated 1,392,840 beneficiaries (5.34%). The total estimated cost to Medicare was $14.3 million, or approximately $10.27 per dose. Crude 4-year rates indicated that white persons were much more likely to be immunized than black persons (5.60% vs 2.94%). Persons 70 through 84 years of age had higher immunization rates than either younger or older beneficiaries. The number of immunizations given peaked in 1986 and declined thereafter. A variety of vaccination strategies that may raise the immunization level in the elderly have been developed. The broad implementation of successful strategies will be important if the goal of a 60% immunization level in the elderly by the year 2000 is to be reached. PMID- 1929688 TI - Adverse behavioral reactions attributed to triazolam in the Food and Drug Administration's Spontaneous Reporting System. AB - Reports of adverse behavioral reactions to triazolam, a triazolobenzodiazepine ultra-short-acting hypnotic, were examined in the postmarketing surveillance Spontaneous Reporting System of the Food and Drug Administration. Reports for triazolam of confusion, amnesia, bizarre behavior, agitation, and hallucinations were compared with reports of these reactions for temazepam, another short-acting hypnotic. Analysis of individual case reports from marketing through 1985 for triazolam vs temazepam showed 133 vs two for confusion, 109 vs three for amnesia, 59 vs two for bizarre behavior, 58 vs four for agitation, and 40 vs one for hallucinations. Considering extent of use, reporting rates for triazolam were 22 to 99 times those for temazepam, depending on the reaction. Reactions to triazolam tended to occur at higher doses and in older patients. This and an updated analysis of aggregate reports for the first 7 years of marketing of each drug with reporting rates and adjustment for various factors suggest a higher occurrence of these reactions with triazolam, but selection factors cannot be completely ruled out. When treating insomnia, physicians should emphasize sleep hygiene practices as alternatives to drug therapy; if drug therapy is required, they should prescribe hypnotics at the lowest recommended doses for the shortest clinically necessary durations and discontinue medication use should any adverse reactions occur. PMID- 1929690 TI - Increasing impact of obesity on serum lipids and lipoproteins in young adults. The Bogalusa Heart Study. AB - Obesity is an important determinant of serum lipids and lipoproteins in adults. Since obesity begins early in life, the impact of obesity of serum lipid and lipoprotein levels was examined in 3311 children and young adults (ages 5 to 26 years) from a totally biracial community. Study subjects were grouped according to race, sex, and age categories (5 to 10 years, 11 to 16 years, 17 to 22 years, and 23 to 26 years), excluding females using oral contraceptives or who were pregnant. Overall, associations increase with age, being most prominently noted in white males. The strong positive relation of ponderosity to low-density lipoprotein cholesterol was indicated in the older age groups with correlation coefficients ranging from r = -.09 in the youngest black males to r = .47 in white males aged 17 to 22 years. A negative association was noted between ponderosity and high-density lipoprotein cholesterol with correlation coefficients ranging from r = .08 in black females aged 17 to 22 years to r = .39 in the oldest white males. Similar results were seen using subscapular skin fold thickness as a measure of central obesity. Overweight was defined as exceeding 20% above the National Health Anthropometric and Nutritional Examination Survey II survey 50th percentiles. The prevalence of overweight individuals increased with age, being most prominent in black females. The percent(s) of hypercholesterolemic cases, based on the National Cholesterol Education Program criteria, likewise increased with age. A marked proportion of older white males were classified as borderline high and high for low-density lipoprotein cholesterol. A regression model using subscapular skinfold to predict serum lipids and lipoproteins within each age group indicated a consistent increase in the adverse nature of the lipid profile. Intervention and education programs aimed at reducing obesity at younger ages are recommended to reduce serum lipid and lipoprotein levels developing in young adulthood. PMID- 1929691 TI - A model of lifetime osteoporosis impact. AB - The study goal was to use population-based data to model aspects of lifetime osteoporosis impact not previously studied, specifically: (1) to estimate person years of fracture-related functional impairment against the trajectory of functional status in the general population; (2) jointly to consider hip, vertebral, and Colles' fractures in estimating the percent of women who will ever fracture; and (3) to estimate the lifetime number of fractures expected in a cohort of 10,000 50-year-old white postmenopausal women. The model estimates that 54% of 50-year-old women will sustain osteoporosis-related fractures during their remaining lifetimes. Beyond the functional impairment expected in similarly aged, unfractured women, osteoporosis-related fractures are estimated to cause 6.7% of women to become dependent in basic activities of daily living; 7.8% are expected to require nursing home care for an average of 7.6 years. PMID- 1929692 TI - Percutaneous injuries among health care workers. The real value of human immunodeficiency virus testing of 'donor' blood. AB - A decision analysis was conducted to examine whether health care workers should receive short-term (42 days) zidovudine treatment following percutaneous exposure to blood, as well as to determine the value of testing "donor" (patient's) blood. Three alternative options were analyzed: treat all, treat none, and test. In the treat all option, all health care workers receive short-term zidovudine therapy immediately after exposure; in the treat none option, no one receives zidovudine; and in the test option, donor blood is tested, and if it is human immunodeficiency virus (HIV) positive, zidovudine is given. Baseline variables were obtained from the literature. Each outcome was expressed as a utility; this is a method of quantifying the values that persons place on different health states. The results showed that the test option was preferred. Sensitivity analyses indicated that even if the risk of seroconversion were zero or the effectiveness of zidovudine were zero or the drug were withheld, this option was preferred, thus indicating some value of testing other than merely identifying health care workers who should receive zidovudine. In the baseline analysis, this was derived from the fact that approximately 95% of the health care workers would be reassured by a negative test; ie, only approximately 5% of donors are HIV positive. If the prevalence of HIV seropositivity exceeded 42%, the treat none option was preferred. This was found to be due to the fact that increased numbers of health care workers would be told that they were exposed to HIV-positive blood. The "worrying factor" associated with such an exposure was such that above 42% HIV seropositivity, the treat none option was preferred overall. Thus, the real value of testing donor blood is in identifying those persons (greater than 95%) who could be told that they were exposed to HIV-negative blood, that is, reducing their worrying factor to zero. Because acquired immunodeficiency syndrome is a fatal disease, and given that zidovudine is the only available therapeutic option at present, the drug has an important role to play if its effectiveness is greater than zero. PMID- 1929693 TI - Transmission of human T-lymphotropic virus types I and II by blood transfusion. A retrospective study of recipients of blood components (1983 through 1988). The American Red Cross HTLV-I/II Collaborative Study Group. AB - We studied results of a "lookback" program involving laboratory testing and interviews of 133 recipients of prior donations from blood donors seropositive for human T-lymphotropic virus types I and II (HTLV-I/II) identified at 28 American Red Cross blood centers. The study was designed to explore the natural course of posttransfusion HTLV-I/II infection among individuals who received blood components from donors subsequently identified as being HTLV-I/II seropositive. Seventeen recipients were seropositive, an apparent transmission rate of 12.8%. Red blood cells and platelets were the implicated components, and red blood cells that were less than 6 days old had a transmission efficiency of 80%. Virus typing enabled documentation of primary and secondary transfusion transmission of HTLV-I and HTLV-II, including the direct transmission of HTLV-II by a donor with a history of intravenous drug use. We conclude that transfusion transmission of HTLV-I/II to approximately 700 recipients per year occurred in the United States before routine donor testing began in 1988. PMID- 1929694 TI - Substantial improvement in compliance with universal precautions in an emergency department following institution of policy. AB - Seven months following the introduction of an institutional policy mandating compliance with universal precautions (UPs), we observed 127 health care workers performing 1421 interventions on 155 critically ill and injured patients in an emergency department setting in July 1989. Results were compared with a similar study undertaken exactly 1 year previously when UPs were considered as guidelines only. Overall adherence to UPs improved from 44.0% to 72.7% from 1 year to the next. Adherence to UPs improved from 19.5% to 55.7% during interventions on patients with profuse bleeding and from 16.7% to 54.5% during performance of major procedures. Compliance improved from 47.9% to 81.0% for emergency department-based health care workers (residents, attending physicians, nurses, x ray film technicians). Prehospital care providers, a group not accountable to the institution, remained particularly noncompliant with only 13% adherence. We conclude that mandating UPs as policy with a monitoring component is effective in ensuring a reasonable level of adherence. However, given current barrier technology, achieving appropriate levels of compliance during unscheduled visits by patients requiring immediate attention and rapid intervention remains a challenge. PMID- 1929695 TI - Community-based plan for treating human immunodeficiency virus-infected individuals sponsored by local medical societies and an acquired immunodeficiency syndrome service organization. AB - Individuals infected with human immunodeficiency virus frequently experience difficulty finding medical care from private physicians. Fear of occupational exposure, prejudice, lack of knowledge, and financial loss have all been cited as reasons for the reluctance of primary care physicians to accept patients with acquired immunodeficiency syndrome into their practices. To meet the medical needs of all patients infected with human immunodeficiency virus, this Virginia community adopted a voluntary rotational referral plan to provide primary care for all such individuals. The program required the cooperation of a voluntary pool of internists and family practitioners and an acquired immunodeficiency syndrome service organization with a volunteer physician advisor to coordinate referrals of unassigned patients. No physician received more than three referrals per year. During the 2 years of operation, 118 referrals were made to 30 physicians. Regular educational seminars were provided with medical updates and consultation support was provided. This locally based program appears to be meeting the acquired immunodeficiency syndrome challenge in this community and may have applicability to other communities as well. PMID- 1929696 TI - Effect of a change in house staff work schedule on resource utilization and patient care. AB - Concern is frequently expressed by health care providers and consumers that the work environment of physicians-in-training may adversely affect their performance. This article documents the effects of changing from a traditional rotational overnight call schedule for house staff to a schedule designed to reduce sleep deprivation, distribute admissions more evenly throughout the week, and improve continuity of inpatient care on the internal medicine service of a large, university-affiliated Veterans Affairs Medical Center. In a prospective, time-series study, the hypothesis that this change would improve the efficiency and quality of medical care was evaluated by comparing the hospital course of the patients admitted during 4-week periods prior to and following the change in work schedule. The patients in the preintervention group do not differ significantly from those in the postintervention group in any identifiable clinical characteristics. The length of stay was shorter (10.9 vs 9.3 days) and the number of laboratory tests ordered per patient was smaller (24.0 vs 19.0) for patients cared for under the new work schedule compared with those cared for under the traditional work schedule. Resident physicians also committed fewer medication errors under the new work schedule (16.9 vs 12.0 per 100 patients discharged). We conclude that altering the house staff work schedule affects patient care and can lead to a decrease in utilization of health care resources. PMID- 1929697 TI - Nonlinear theophylline pharmacokinetics. A preventable cause of iatrogenic theophylline toxic reactions. AB - When theophylline is used for the treatment of patients with obstructive pulmonary diseases, most clinicians attempt to maintain serum levels between 55 and 110 mumol/L because higher levels are associated with an increased risk of serious toxic effects. Nonlinear theophylline kinetics are known to occur in animals, in some pediatric patients, and at very high toxic levels in adults. However, within the usual therapeutic range of serum levels, first-order kinetics are assumed to operate, and, thus, a one-compartment model or a model-independent approach is routinely used for dose adjustments. We have recently encountered two adult patients in whom nonlinear theophylline kinetics existed within the subtherapeutic and therapeutic range of serum levels. In both cases this was not immediately recognized by the clinician, resulting in prolonged use of subtherapeutic doses of theophylline. In addition, in one case our empiric attempts to achieve therapeutic serum levels resulted in serious theophylline toxicity. We present only the data from this latter patient to be used as a case study. Based on this example and a review of the literature, we propose that to avoid such a potentially fatal complication the following steps should be taken when dealing with a patient in whom serum theophylline levels fail to rise as expected with increasing oral doses: (1) supervised administration of oral theophylline to rule out noncompliance; (2) discontinuation of further empirical increases of the oral dose of theophylline; (3) obtention of steady-state serum levels on at least two different oral doses of theophylline; and (4) calculation of the appropriate maintenance dose of theophylline for that individual patient using any of the methods cited in this report. PMID- 1929698 TI - Pneumothorax after thoracentesis. PMID- 1929699 TI - Complications associated with thoracentesis. PMID- 1929700 TI - Tuberculosis, the captain; pneumococcus a lieutenant. PMID- 1929701 TI - Vasopressin therapy of hemorrhagic complications following coronary artery bypass grafting. PMID- 1929702 TI - Decision analysis, public health policy, and isoniazid chemoprophylaxis for young adult tuberculin skin reactors. PMID- 1929703 TI - The isoniazid debate. PMID- 1929704 TI - Clubbing in hypersensitivity pneumonitis. PMID- 1929705 TI - Distribution of parvalbumin-immunoreactivity in the rat thalamus using a monoclonal antibody. AB - 1. The distribution of parvalbumin cell bodies and fibers in the thalamus of the rat was studied using a monoclonal antibody and the avidin-biotin-peroxidase method. The densest clusters of immunoreactive perikarya were observed in the nuclei ventralis posterior, reticularis, ventralis anterior and zona incerta, whereas the nuclei habenularis lateralis, lateralis posterior, lateralis, centralis lateralis and ventralis lateralis had the lowest density. In the nucleus geniculatum laterale ventralis, the density of parvalbumin cell bodies was intermediate. In all these thalamic nuclei, small, round or fusiform immunoreactive cells with short immunolabeled dendritic processes were observed. 2. The densest network of immunoreactive fibers was observed in the nuclei geniculatum laterale ventralis, reticularis and zona incerta. The nuclei geniculatum laterale dorsalis, ventralis posterior, medialis ventralis, ventralis anterior, anterior ventralis, anterior dorsalis and rhomboidens contained a moderate number of parvalbumin fibers, whereas the nuclei lateralis posterior, habenularis lateralis, parataenialis, centrum medianum, lateralis, centralis lateralis, ventralis lateralis, medialis dorsalis, anterior medialis, ventralis medialis and lateralis anterior had the lowest density of immunoreactive fibers. In addition, a large number of immunoreactive fibers was found in the lemniscus medialis and a scarce number in the stria medullaris. 3. No immunoreactive structure was observed in the nuclei habenularis medialis, paraventricularis, reuniens and geniculatum mediale. 4. Thus, perikarya and fibers containing parvalbumin are widely distributed throughout the thalamus of the rat, suggesting that parvalbumin might play a role, directly or indirectly, in limbic, visual and somatosensory mechanisms. PMID- 1929706 TI - The effects of lesioning both the superior colliculus and the substantia nigra of cats on turning behavior. AB - In twenty two adult cats, distributed in four groups, stainless steel electrodes were implanted in the superior colliculus and the substantia nigra of both sides in order: 1) to find the current intensity threshold values necessary to evoke turning behavior, and record their variations after lesion of the cited structures; 2) to study the effects of lesioning two of these structures, specifically related to the direction of turning behavior, and 3) to assess the time-course of recovery from postural asymmetry after damaging two structures involved in rotation behavior, located either in the same or in the opposite side, as well as the importance of performing these lesions simultaneously or at different periods. Three main results were observed: 1) a large proportion of lesioned cats showed an increase in threshold values necessary to evoke rotation of the implanted structures located either in the same or in the opposite side; 2) the lesions induced in a significant number of cats a transient postural asymmetry. After lesioning the superior colliculus, the direction of turning was towards the damaged hemisphere. Apomorphine injected fourteen days later demonstrated the existence of an occult asymmetry, and the direction of turning was maintained. In the substantia nigra lesioned animals, the direction of turning, was towards the non-lesioned side. Apomorphine reversed the direction of turning; 3) the cats showed a remarkable capacity to recover from the postural asymmetry produced by the lesion. This experimental series further support the hypothesis of a close functional relationship between structures of both cerebral hemispheres related to turning behavior. PMID- 1929707 TI - Historical development of current concepts on central chemosensitivity. AB - The history of concepts on the mechanism of central chemosensitivity is reviewed with special emphasis on ideas that have remained valid or stimulating until today. Early physiologists considered chemoreception to be a property of respiratory neurones in the brainstem (Pfluger 1868; Gesell 1926, 1949; Winterstein 1910, 1921, 1956). It has not been elucidated by which mechanism acid/base disturbances cause cardiorespiratory adaption. The reaction theory focused on protons as being the decisive stimulus (Lehmann 1888, Winterstein 1921, Loeschcke 1982), but this issue can be adequately discussed only when the compartment where changes occur is taken into account (Jacobs 1920, Gesell 1940). Heymans and collaborators demonstrated in 1930 that chemoreception is not only possible by a central mechanism but also at the level of the peripheral chemoreceptors. Without solid evidence for such an assumption, the existence of specific 'receptors' for pH and/or pCO2 was postulated by von Euler and Soderberg in 1952. Several chemosensitive areas at the ventrolateral surface of the medulla oblongata were defined by Loeschcke and collaborators in a series of papers after 1958. Within these areas, however, a specific chemoreceptor has not been distinguished. On the other hand, a direct chemosensitivity of bulbospinal sympathoexcitatory neurones as an intrinsic property of these neurones has recently been demonstrated (Seller 1989). Therefore, coming back to the original concept of chemoreception as a function of central cardio-respiratory neurones appears to be the most promising path for future research. PMID- 1929709 TI - [Oral propranolol in Wolff-Parkinson-White syndrome. Electrophysiological data]. AB - The effects of oral propranolol were studied in 24 patients with the WPW syndrome. The average daily dose of propranolol was 130 +/- 24 mg administered in 3 doses over a period of 48 to 72 hours. Endocavitary electrophysiological study was performed 2 to 4 hours after the last dose. The effective anterograde refractory periods (EARP) of the accessory and normal pathways were measured before and after propranolol (and, in both studies, before and after isoproterenol). The EARP of the accessory pathway was not affected by the propranolol. However, in the 9 patients in whom its value was less than 270 ms, it increased significantly (p = 0.01). The EARP of the accessory pathway measured after administration of isoproterenol increased significantly in all patients with oral propranolol (p = 0.001). Sustained reciprocating tachycardia could be induced in 19 patients and non-sustained reciprocating tachycardia in 5 other patients during base line electrophysiological study. Oral propranolol prevented the induction of the tachycardias in 18 patients (75%), even after isoproterenol. The shortest R-R interval between two pre-excited complexes in atrial fibrillation increased after propranolol (283 +/- 45 to 343 +/- 95 ms). These results show that oral propranolol increases the EARP of the accessory pathway and the shortest R-R interval between two pre-excited complexes in atrial fibrillation in patients with short anterograde refractory periods of their accessory pathways, and is effective in preventing reciprocating tachycardia. Oral propranolol may be useful and can be used safely in patients with the Wolff Parkinson-White syndrome. PMID- 1929708 TI - [Prognosis of ischemic mitral valve insufficiency]. AB - Seventy-nine patients with ischemic mitral regurgitation were followed up for a period of 20 +/- 8 months. The risk of death increased with age and cardiac failure at the time of inclusion. The risk of cardiac events increased with these factors and also with raised serum creatinine and decreased echocardiographic fractional shortening. The global 2 year survival was 72.8% and survival without a further cardiac event was 48.7%. Surgery and angioplasty increased global survival and freedom from cardiac events of patients with severe regurgitation (74.9% and 68.8% versus 59.4% and 46.1% for medical therapy alone). The functional improvement was also greater in patients undergoing surgery or angioplasty (80% of patients in NYHA Stage I versus 53.8% in the medical group). Angioplasty was only performed in cases of paroxysmal mitral regurgitation by reversible papillary muscle ischemia. Surgery (coronary bypass usually associated with mitral valve replacement) was associated with better results than medical therapy alone in permanent mitral regurgitation by papillary muscle dysfunction or rupture. Despite a high immediate mortality, this option should be considered rapidly in cases of severe ischemic mitral regurgitation with pulmonary oedema. PMID- 1929710 TI - [Chronology of maximal surface area and peak velocities of left heart valve flow jets using Doppler imaging. Clinical implications]. AB - The aim of this study was to correlate the timing of the maximal surface area of the jet recorded by color flow Doppler and the peak velocities recorded by continuous mode Doppler with reference to the ECG R wave to determine whether standardisation of the chronologies of measurements was possible. A comparative paired study of these two parameters was undertaken in 44 subjects who had 55 left heart valvular lesions, all in sinus rhythm and, in cases of regurgitation, with pansystolic or pandiastolic regurgitant flow. The jets were examined in the inflow chambers of valvular insufficiency and at the origin of the jet in the short axis for stenotic lesions and aortic regurgitation, with planimetry of the cross sectional area in color Doppler. The correlation coefficient was 0.85 for aortic stenosis, 0.96 for mitral stenosis, 0.84 for aortic regurgitation but only 0.10 for mitral regurgitation. The mean values of the two chronologies were identical for stenotic lesions and did not differ significantly in regurgitation even at the mitral valve. However, the individual differences between the two chronologies exceeded 20 ms in 63% of aortic and 91% of mitral regurgitations. The maximal surface areas of the jets of 45% of aortic regurgitant and 91% of mitral regurgitant lesions were recorded between the onset of regurgitation and the peak jet velocity. The differences in chronology of the two parameters studied in cases of valvular regurgitation indicate the multifactorial nature of color flow jet imaging, probably associated with individual physiopathological variations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929711 TI - [Sequential revascularization of anterior myocardium using the internal mammary artery. A year-long clinical and angiographic follow-up]. AB - One hundred and twenty-one consecutive patients (104 men, 17 women; mean age 56 +/- 7.8 years) underwent sequential mammary artery grafting for anterior (left anterior descending or diagonal arteries) wall revascularisation. There was one death (0.8%) and five myocardial infarctions (4.2%) including two anterior infarcts during the first 30 postoperative days. All survivors were reviewed at one year. Of these 120 patients, 77 (64%) accepted control coronary angiography on average 456 +/- 143 days after surgery. One internal mammary artery anastomosed to 2 diagonal arteries was occluded. All the other latero-lateral anastomoses were patent. There was, however, one 60% stenosis. Three termino lateral anastomoses on the left anterior descending artery were occluded and 2 others stenosed (40% and 60% luminal narrowing, respectively). Four internal mammary arteries were narrowed 2 because of stenosis and 2 because of the small calibre of the receiving artery. The patency rate considering the total number of anastomoses was therefore 96.8%. These results show that sequential internal mammary artery grafting for myocardial revascularisation does not increase the number of perioperative complications and is associated with a low rate of occlusion on the left anterior descending artery at one year. This surgical technique may therefore be used routinely. PMID- 1929712 TI - [Comparative, clinical and echocardiographic study of the Bex and De Vega annuloplasties]. AB - A retrospective study of 27 cases compared the long term clinical and echocardiographic results of tricuspid valve annuloplasty by the Bex (15 patients) and the De Vega (12 patients) techniques. All patients were in NYHA Classes III or IV before surgery. There was associated mitral valve disease in 24 cases and mixed mitral and aortic valve disease in 3 patients requiring valve replacement. The follow-up period ranged from 3 to 106 months (average 48 +/- 4 months). All patients underwent clinical and color Doppler echocardiographic evaluation. There was symptomatic improvement after surgery as all patients recovered to NYHA Classes I or II. An echocardiographic classification was adopted to assess residual tricuspid regurgitation. The leak was judged to be significant when the surface area of the jet was greater than 5 cm2. Two thirds of patients (17/27) had no significant residual tricuspid regurgitation with the Bex or de Vega techniques of tricuspid annuloplasty according to this criterion. However, significant residual tricuspid regurgitation was observed in 37% of patients (10/27) even though they were all clinically improved. A comparison of the echocardiographic parameters including the severity of residual tricuspid regurgitation, the left and right atrial dimensions, the right ventricular dimensions and tricuspid valve pressure gradients did not show any significant long term difference between the Bex and the De Vega tricuspid annuloplasties. PMID- 1929713 TI - [Retrograde cardioplegia through the coronary sinus in the surgery of the aortic valve. A clinical study of 500 patients]. AB - Over the last few years there has been a renewal of interest in retrograde administration of cardioplegic solutions but this method has not been validated by a large scale clinical trial. From 1980 to 1989 our group used retrograde coronary sinus perfusion as the only means of administering cardioplegia in 500 consecutive patients undergoing isolated aortic valve replacement (AVR) (359 cases) or associated with another valvular or myocardial revascularization procedure (141 cases). Using this method, there were 31 hospital deaths (6.2%) of which 20 were of cardiac origin (4%). During the last 5 years, hospital mortality for isolated AVR decreased to 1.5%. With an incidence of low cardiac output of 12%, of arrhythmias and atrioventricular block of 7.4% and 1.2% respectively, and of myocardial infarction of 1.4%, this method of cardioplegia compares favourably with anterograde perfusion. There were only 3 traumatic lesions of the coronary sinus, all occurring at the beginning of the series and all of which were successfully repaired. Retrograde coronary sinus perfusion is therefore a safe and effective method of cardioplegia during aortic valve surgery: the cardioplegic solution is distributed uniformly in patients with coronary artery disease and therefore, this could become the technique of choice for myocardial protection in coronary artery or mixed coronary and valvular surgery. PMID- 1929714 TI - [Atrial electrophysiological study of unexplained cerebrovascular disorders]. AB - The aim of this study was to detect possible atrial electrophysiological abnormalities in patients with unexplained embolic cerebrovascular accidents without overt atrial arrhythmias. This group was compared with normal controls and a group of patients with paroxysmal atrial fibrillation. Sixty-six patients were studied: Group I normal controls (N = 20); Group II patients with CVA (N = 26) and Group III, patients with paroxysmal atrial fibrillation (N = 20). Each group was divided into 2 subgroups according to age (over and under 45 years). The following parameters were taken into consideration: parameters correlated to atrial excitability (effective and functional refractory periods, adaptation of these refractory periods, intraatrial conduction--A1 and A2, S1A1, S2A2 intervals -, index of latent vulnerability); provocative testing by the extrastimulus technique; classical indices of atrioventricular conduction and sinus node function. In subjects over 45 years of age, the effective refractory periods were shorter in Group III (214 +/- 33 ms) and II (214 +/- 32 ms) than in the control Group I (248 +/- 21 ms), p less than 0.01. This difference was not apparent in younger patients. Inadaptation of the refractory periods was demonstrated equally in Groups II and III in all ages whilst the control subjects showed normal adaptation, p less than 0.05. Intraatrial A1 and especially A2 conduction was significantly prolonged in Group III (94.5 +/- 24 ms) and II (87 +/- 14 ms) compared with the control group (69 +/- 8 ms), p less than 0.01, especially in younger subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929715 TI - [Determination of transmitral blood flow by pulsed echodoppler. Correlation with aortic blood flow in 30 patients]. AB - The aim of this study was to assess the validity of mitral valve blood flow measured by pulsed Doppler echocardiography (PDE) with the sample volume positioned at the tips of the mitral leaflets. Thirty patients with a mean age of 38.4 years underwent calculation of transmitral blood flow: by Touche's method (A) in which the mitral orifice is assumed to be an ellipse with a constant long axis equal to the diameter of the mitral annulus and a variable short axis equal to the distance between the mitral leaflets measured on the M mode recording. The velocities are recorded by PDE with the sample volume at the tips of the mitral leaflets. The instantaneous cardiac output is equal to the surface multiplied by the instantaneous velocity. The integration of the instantaneous outputs throughout the whole of diastole by a computer programme provides the stroke volume; by a simplification of this method (B) which considers the short axis of the mitral ellipse to be constant and equal to the mean mitral valve leaflet separation measured from the M mode recording, and; by Hoit's method (C) which calculates mitral valve surface area from the M mode recording alone. The transmitral blood flow was calculated by these three methods and compared to the classical PDE aortic cardiac output measurement during the same examination, the accuracy of which has been previously demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929716 TI - [Dissection of aorta after aortic valve replacement]. AB - The authors report 4 cases of aortic dissection after aortic valve replacement. The aorta was dilated in all four cases before surgery. Two patients died within hours of the dissection, illustrating the poor prognosis of this complication and the difficulties of surgical management. The features of these four cases were compared to those of 29 other cases reported in the last ten years. The initial surgical indication for valve replacement was equally divided between aortic stenosis and regurgitation. The onset of dissection after surgery was very variable, ranging from a few hours to several years after valve replacement. Abnormalities of the aortic wall and peroperative trauma play an important role in the pathogenesis of this complication. The prognosis is very poor, which underlines the importance of preventive measures and regular follow-up of these patients. PMID- 1929717 TI - [Mitral valve prolapse: a benign abnormality?]. AB - Mitral valve prolapse should be considered a benign condition as there are few complications. The natural history is not significantly different to that of a matched control population. There are potentially severe forms of the condition which are mainly observed in specialised centres and this introduces a bias in patient selection when compared with the general population. These forms are relatively rare in clinical practice and can be easily identified by simple echocardiographic criteria of valvular thickness. In any case, patients with mitral valve prolapse should be reassured in order not to create or unduly increase anxiety which in itself may cause incapacity. PMID- 1929718 TI - [Mitral valve prolapse: a severe abnormality?]. AB - The reputation of mitral valve prolapse being a benign condition is based to a great extent on the fact that complications are rare in minor forms, but also because a number of studies of the condition included normal subjects, especially of the female sex. The prevalence of mitral valve prolapse in the general population is 4 to 5%. Approximately 20% of these patients have marked redundancy of valve tissue and are particularly exposed to complications. The incidence of infective endocarditis in cases with an audible murmur is 0.05% per year. The incidence of mitral regurgitation increases with age, so that the annual probability of surgical correction is 0.03%. The risk of sudden death in cases without mitral regurgitation is low (2/10,000 per year) but it is 50 to 100 times greater when mitral regurgitation is present. The frequency of arrhythmias is also higher in cases with mitral regurgitation and that of cerebro-retinian ischemia is estimated to be 0.02% per year. Therefore, a serious complication (endocarditis, sudden death, surgical mitral regurgitation, cerebral or retinian ischemia) occurs each year for every 1,000 mitral valve prolapses, or for a population of 25,000 inhabitants. PMID- 1929719 TI - [Acute rheumatoid aortic insufficiency treated by valve replacement. Apropos of a case]. AB - Rheumatoid valvular heart disease and aortic valve replacement for a rheumatoid lesion have been previously reported in the literature. The authors report the first case of emergency surgery for acute aortic regurgitation due to necrosis and rupture of a rheumatoid granuloma: the anatomopathological lesions observed were patholognomic. PMID- 1929720 TI - [Retrograde dissection of the common trunk of the left coronary vessel during angioplasty of left anterior descending coronary artery. Apropos of 2 cases]. AB - Acute dissection of the left main coronary artery during coronary angiography or angioplasty is a rare but well known complication; it is attributed to a mechanical trauma caused by the tip of the catheter guide wire. The authors present two cases of dissection at the site of coronary angioplasty with a retrograde extension to the left main stem requiring emergency coronary surgery. PMID- 1929721 TI - [Coronary spasm and diffuse coronary vasoconstriction responsible for transient left ventricular insufficiency]. AB - A 52 year old patient presenting with spontaneous anginal chest pain for 4 days was admitted to hospital for a more intense and prolonged chest pain associated with signs of left ventricular failure (gallop, pulmonary crepitations, hypoxemia). Coronary angiography showed marked septal hypokinesia and spontaneous localised spasm of the left anterior descending and marginal arteries with a variable degree of luminal narrowing of the other segments of these two arteries and of the right coronary artery. These changes regressed after intracoronary injection of molsidomine. The signs of left ventricular failure disappeared in 48 hours. The wall motion abnormality, monitored by 2D echocardiography, regressed slowly over 3 days. On the other hand, the electrocardiogram, which showed anterior wall subendocardial ischaemia with prolongation of the QTc interval during the spasm, remained abnormal for a long time. Therefore, in the absence of organic heart disease, coronary spasms associated with vasoconstriction can induce a sufficiently severe and durable alteration of left ventricular function to create clinical signs of cardiac failure and profound and prolonged ST-T wave changes on the electrocardiogram. PMID- 1929722 TI - [Fulguration of atrial flutter in man. A pathological case]. AB - A 63 year old man with ischemic heart disease underwent two sessions of catheter ablation in the inferior right atrium for poorly tolerated resistant and recurrent atrial flutter. After endocavitary mapping and comparison with surface recordings of the f waves, a shock of 50 joules was delivered to the zone situated anteriorly to the inferior vena cava, under the orifice of the coronary sinus and behind the tricuspid valve. Early recurrence of the arrhythmia led to a second attempt and another 50 joules shock was administered to the same area. Another short term recurrence led to definitive nodohisian interruption with a 270 joules shock. Thirty months later, the patient died suddenly during an episode of cardiac failure. Macroscopic examination of the right atrium showed a zone of parietal congestion measuring 4 x 3 cm with a very thin, translucid, central zone measuring 3 x 1.5 cm, just anterior to the inferior vena cava in the right atrial free wall. Histological examination of this zone showed an intense, mutilating fibrosis dissociating the muscular fibres, of the pectinate muscle and even replacing the myocardium in certain regions. In the Eustachian valve, there were muscular fibres, probably representing the posterior internodal pathway, which were also fibrosed. These observations suggest that: 1) in view of the extreme thinness of the atrial wall at the site of ablation there is a high risk of perforation even when right endoatrial catheter ablation is performed with low energy shocks; 2) the posterior internodal pathway does not seem to be an essential component for atrial flutter. PMID- 1929723 TI - [Are ethics committees in pediatrics specific? Reflections apropos of their roles]. PMID- 1929724 TI - [Corticotherapy and acute subglottic laryngitis]. PMID- 1929725 TI - [Infant feeding until the age of 4 months old in Seine-Maritime]. AB - This study reports infant feeding practices during the first 4 months of life. A representative sample of 10% of the births in the Seine-Maritime department formed the subject of a questionnaire cohort study carried on at home by public health institution for infants specialized nurses. Among 1,407 interviewed mothers, 52% had been thinking about their future child feeding before birth, essentially with their circles, especially their husbands. The type of feeding had been chosen before pregnancy in 64.3% of cases. Earlier choices resulted more often in breast-feeding. 46.2% of mothers tried to breast-feed their children, however 17% among them discontinued when back home. Carrying out breast-feeding (median duration 10 weeks) delayed the feeding diversification and was associated with a lower frequency of health difficulties in children. PMID- 1929726 TI - [Fetal toxoplasmosis. In utero treatment with pyrimethamine sulfamides]. AB - The mothers of 52 cases of toxoplasmic fetopathy diagnosed in utero by fetal blood and/or amniotic fluid sampling were treated with the combination pyrimethamine-sulfadiazine (or sulfisoxazole) and by spiramycine. The infants were compared with 51 other infants with congenital toxoplasmosis whose mothers had received spiramycine alone. Patients of both groups received the same pyrimethamine-sulfadiazine and spiramycine treatment after birth. Parasitologic examination of the placenta was positive in 42 and 76.6% of patients, in group I and group II respectively. The newborns had specific IgM in 17.4 and 69.2% of cases respectively in both groups. These differences were significant. The mean specific IgG titer was significantly reduced at birth and 4 to 6 months of age in the first group. Patients in group I had more often subclinical infection than patients of the comparison group: 57% vs 33.3%. They had less often a high cerebro-spinal protein content during the first week. Prenatal treatment with pyrimethamine-sulfadrugs resulted in a less progressing infection at birth. However in cases with clinically patent toxoplasmosis, the frequency of overt localizations and their sequellae was not significantly altered. This might be related to a relatively late onset of the treatment. The pyrimethamine-sulfadrug combination given to mothers of proved infected fetuses can be rewarding. The indication might be extended to well-documented seroconverted mothers if, in the future, the acquired experience and necessary pharmacological studies bring the proof of its innocuousness. PMID- 1929727 TI - [Factors associated with low birth weight in Tunisian Sahel]. AB - The aim of this study, which was carried out in the area of Monastir from September 1st to December 31, 1989 was to evaluate the incidence of and to identify the factors associated with low birth weight (LBW). The results showed that LBW neonates make up 7.6% (n = 413) of the 5,419 live births, 57.4% of which being small for dates at term. 48% of prematures also had intra-uterine growth retardation. The average LBW was 1,913 +/- 497 g (20% of the LBW neonates had a weight below 1,500 g). Factors associated with LBW were: extreme ages of the mothers, illiteracy, working class, previous history of stillbirth or death before 1 year of age, abnormal issue of the previous pregnancy, multiple pregnancies, insufficient medical supervision and prenatal care, congenital malformations in the child. Improvement in prenatal care and adequate monitoring of at risk pregnancies might decrease the occurrence of LBW in this Tunisian area. PMID- 1929728 TI - [N-acetylaspartic aciduria. Clinical, biological and physiopathological study]. AB - Two cases of N-acetylaspartic aciduria in siblings are described and compared to the 18 cases already reported. The disease should be considered in childhood when a syndrome of severe encephalopathy with macrocephaly, blindness caused by optic atrophy and diffuse leucodystrophy on CT scan occurs. Urinary organic acids gas chromatography confirms the diagnosis. It is probably inherited as an autosomal recessive trait. Aspartoacylase activity deficiency has been reported and this assay could possibly be used for prenatal diagnosis. Pathogenesis is not clearly understood but N-acetylaspartic acid (NAA) seems to be essential for central nervous system myelination. Clinical and anatomic features of N-acetylaspartic aciduria are very similar to Van Bogaert-Bertrand disease (cerebral spongy degeneration or Canavan disease) but heterogeneity of this disease cannot excluded. PMID- 1929729 TI - [Orbital and muscular relapse of Burkitt's lymphoma]. AB - We report the case of a child presenting with abdominal Burkitt's lymphoma in whom a relapse presented as orbital and muscle involvement. This clinical feature is extremely rare. Two muscle and one orbital biopsies were necessary to obtain proper diagnosis. A new extension check-up showed bone marrow invasion and normal cerebrospinal fluid. This relapse was successfully treated by conventional chemotherapy and consolidated with high-dose chemotherapy, total body irradiation and autologous bone marrow transplantation. Eighteen months after transplantation, the child may be considered as definitively cured. PMID- 1929730 TI - [Listeria monocytogenes nosocomial infection in the maternity ward]. AB - Nosocomial infection with Listeria monocytogenes 4b occurred in January 1990 in a maternity hospital in Grenoble. The 3 patients involved were born within a 24 hour-interval. The premature newborn responsible for contamination was asymptomatic. Two other newborns without any perinatal infectious risk presented with meningitis, one on the 5th day of life in the maternity hospital, the other one on the 11th day while already at home. The 3 strains of Listeria had the same serovar and lysovar. Epidemiologic investigations led to suspect a contamination in the delivery room and during the care of the children. Strict respect of hygiene orders is imperative to avoid nosocomial infections. PMID- 1929731 TI - [Iconographic rubric. Teratoma of the nasopharynx in a newborn infant]. PMID- 1929732 TI - [Sleep obstruction apnea syndrome in infants and children]. PMID- 1929733 TI - [Intensive phototherapy for neonatal icterus]. PMID- 1929734 TI - [Sleeping position and sudden infant death]. PMID- 1929735 TI - [Chronic intestinal pseudo-obstruction syndrome and associated neurological involvements]. PMID- 1929736 TI - [Acute tubular necrosis during a treatment with Bactrim]. PMID- 1929737 TI - [Late neonatal Streptococcus B infection in Yaounde. Apropos of 46 cases]. PMID- 1929738 TI - [Digestive disorders and transfusion in premature infants]. PMID- 1929739 TI - [Normal glycemia and high glycosylated hemoglobin in a diabetic child]. PMID- 1929740 TI - [Colonic Crohn's disease and congenital galactosemia. Incidental or causal association?]. PMID- 1929741 TI - [Consider cockroach hypersensitivity in children]. PMID- 1929742 TI - [Extracorporeal respiratory assistance]. PMID- 1929743 TI - [Neonatal screening of congenital adrenal hyperplasia. Feasibility, value, conditions]. PMID- 1929744 TI - [Ethical and practical complications in pediatrics of the law concerning protection of people consenting to biomedical research]. PMID- 1929745 TI - [Congenital hypothyroidism. Therapeutic strategy at the early stage of treatment]. AB - The aim of this work was to determine the optimum dosage of L-thyroxine (L-T4) given to infants with congenital hypothyroidism (CH). Thirty seven hypothyroid infants diagnosed through the French screening programme for CH have been treated in our clinic. The study analysed the biochemical parameters (TSH, FT4, FT3) and the L-T4 doses during the first year of life. Treatment was started at 23 days of age (range: 13 to 37). A dose of 7.5 micrograms/kg/d of L-T4 was given at diagnosis. After 2 weeks of treatment, FT3 was normal and FT4 at the upper limit of the normal values. At that time, TSH plasma levels were normal (less than 6 micro UI/ml) in 47% of cases. After 1.7 month of treatment, 22% of patients had TSH levels greater than 10 micro UI/ml despite normal FT4 and FT3. This group of patients, despite being given an identical L-T4 dose, had a significantly lower FT4. They were not different from those who normalized TSH levels in terms of etiology, delayed bone maturation and levels of FT4 or FT3 at diagnosis. In conclusion, an initial dose of 7.5 micrograms/kg of L-T4 normalized FT4, FT3 and TSH in 80% of our patients. Twenty percent of patients seem to need more L-T4 to bring TSH levels back to normal at the end of the second month of treatment. PMID- 1929746 TI - [Life experience by children with brain tumors]. AB - The long-term evolution (intellectual, affective, social) of children cured of their cerebral tumor is far from being satisfactory, despite progress in neurosurgery, chemotherapy and radiotherapy. The feelings of these children and of their family have rarely been studied. The author, on the basis of 60 interviews with such children and their parents, pinpoints the great violence of feelings and situations: feelings of terror, of non-sense, disturbance of the feeling of identity, breaking of relationships, loss of time landmarks. The psychological consequences can be severe: such as being enclosed in a frozen time wrap, and experiencing a lack of social life. If we knew the feelings of these children better, then we could start preventive actions (psychotherapy and specialized rehabilitation) early enough to avoid sequels which cannot be attributed, for all of them, to cerebral damage. PMID- 1929747 TI - [Food habits and consumption of French adolescents. Synthesis of recent surveys]. AB - Studies concerning French adolescents' eating habits have been published during the past four years. The review of such studies shows that nutrient intakes and food consumption are close to those of the adult population. Only the amount of nutrients especially with respect to lipids seems to be more satisfactory than in adults. This observation emphasizes the importance of familial environmental as the main factor of eating habits. French adolescents eat as the preceding generation even if some behaviors (snacks, fastfood) may appear very different from those in adults. However, this similitude does not imply that such habits are satisfactory. PMID- 1929748 TI - [Development of the mortality in premature infants from 32 weeks gestation and below in Fort-de-France]. AB - The mortality rate of prematures of gestational age less than or equal to 32 weeks during hospitalization in the neonatal intensive care unit of the University Hospital in Fort-de-France (Martinique, French Caribbeans) decreased from 69% in 1980 to 32% in 1987-1988 and to 20% in 1989. The mortality of small for gestational age children during the cumulated years 1987-1988-1989 was twice that of babies with normal birth weight. The various factors responsible for these facts were reviewed: caesarean section rates increased from 15% in 1980 to 42% in 1989, percentage of children submitted to assisted ventilation increased from 35% in 1980 to 78% in 1989 and mortality rate related to hyaline membrane disease decreased from 100% in 1980 to 33% in 1989. The comparison with a survey performed in 1985 in the Paris area showed no significant difference with the mortality rate of premature infants of gestational age greater than or equal to 27 weeks born in the University Hospital in Fort-de-France. Therefore an important effort remains necessary concerning mostly children under 27 weeks of gestational age. PMID- 1929749 TI - [Early severe spinal lesions in Bourneville's tuberous sclerosis]. AB - An exceptional case of tuberous sclerosis with marked extensive lesion of the spine in the first year of life is reported. This lesion required orthopedic treatment at the age of 3 years and surgery at the age of 6 years. PMID- 1929750 TI - [Palpebral edema with fever and Streptococcus sanguis septicemia]. AB - A case of facial cellulitis complicated by regional thrombophlebitis and septicemia is reported in a 6 year-old girl. Streptococcus sanguis, a bacterial agent, unusually responsible for cellulitis, was isolated from 5 blood cultures. This child had no immunosuppression or endocarditis or dental infection. She had been previously given a non-steroidal anti-inflammatory agent, which was potentially responsible for the diffusion of infection. PMID- 1929751 TI - [Iconographic rubric. A case of ethmoid mucocele in a 5 year old child]. PMID- 1929753 TI - [Pediatric immunology. Immune deficiencies]. PMID- 1929752 TI - [Hypophosphatemia. Clinical and biological consequences, diagnostic and therapeutic strategies]. PMID- 1929754 TI - [Aberrant left pulmonary artery and tracheo-bronchial abnormality]. PMID- 1929755 TI - [Estimation of plasma and urine osmolality from ionograms]. PMID- 1929756 TI - [Study of platelet-activating factor (PAF) in stools of newborn infants with hemorrhagic colitis]. PMID- 1929757 TI - Magnetic resonance imaging abnormalities in lenticular nuclei and cerebral cortex in schizophrenia. AB - Neuropathologic and brain imaging studies have produced evidence of brain abnormalities in schizophrenic patients, often within the cerebrum's limbic lobe, and, less frequently, within basal ganglia. In the present study we used magnetic resonance imaging morphometric techniques to estimate volumes of specific cerebral structures in schizophrenic patients and age- and sex-matched normal controls. Estimates of the volume of mesial temporal lobe structures were reduced and estimates of the volume of the lenticular nucleus were increased in the schizophrenic patients. There was also evidence of reduced cranial volume in some schizophrenics. The magnitude of the lenticular abnormality, but not the temporal lobe abnormality, was associated with age at first psychiatric contact; earlier onset was associated with larger lenticular nuclei. The possible relevance of these results to neurodevelopmental hypotheses about the pathogenesis of schizophrenia is discussed. PMID- 1929758 TI - The generalized pattern of neuropsychological deficits in outpatients with chronic schizophrenia with heterogeneous Wisconsin Card Sorting Test results. AB - Forty schizophrenic outpatients and 40 normal subjects were assessed using extensive clinical (eg, Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms) and neuropsychological (extended Halstead-Reitan Battery) measures. The schizophrenic patients had multiple neuropsychological deficits on tests of complex conceptual reasoning, psychomotor speed, new learning and incidental memory, and both motor and sensory-perceptual abilities. Neuropsychological impairment correlated more strongly with negative than positive symptoms. Overall, the schizophrenic outpatients showed relatively modest increases in the number of perseverative responses on the Wisconsin Card Sorting Test of abstraction flexibility. A subgroup of these schizophrenic patients seemed to be particularly impaired on the Wisconsin Card Sorting Test. This pattern of results, in conjunction with previous studies, supports the idea that, while some schizophrenic patients may have fixed, frontally based dysfunctions, these dysfunctions may be most prominent, and even fixed, in deteriorated, kraepelinian patients. These data provide evidence for diffuse and far-reaching deficits in a majority of outpatients with chronic schizophrenia. PMID- 1929759 TI - Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees. AB - Several psychophysiological abnormalities associated with schizophrenia have been proposed as genetic trait markers of vulnerability to the disorder. Smooth pursuit eye tracking dysfunction and abnormal long latency event-related potentials are the most promising candidates. Both are independent of the effects of psychotropic medication or mental state at the time of testing, and twin studies demonstrate that each has a high level of heritability. Having recorded smooth pursuit eye tracking and event-related potentials in 20 high-density schizophrenic families, we find abnormalities in one or both measures in most of the families studied. The abnormalities, when present, occur in the family members with schizophrenia and other forms of functional psychosis, and they have a bimodal distribution with approximately half the nonschizophrenic relatives also showing eye tracking dysfunction and/or abnormal event-related potentials. Some of these relatives had psychiatric symptoms; others were normal. Our results suggest that psychophysiological examination can help to clarify the boundaries of schizophrenia spectrum disorder. By helping to decide the phenotypic status of nonschizophrenic family members, this should increase the power of DNA linkage studies. PMID- 1929760 TI - Effects of neuroleptic treatment on symptoms of schizophrenia and plasma homovanillic acid concentrations. AB - Measurement of plasma concentrations of the dopamine metabolite, homovanillic acid, is an indirect tool to assess changes in dopamine turnover in schizophrenic patients. Plasma homovanillic acid concentrations have been reported to decrease during neuroleptic treatment, with the decrement correlating with symptomatic improvement in symptoms of schizophrenia. The present study tested the hypothesis that neuroleptic drugs decrease plasma homovanillic acid concentrations in those schizophrenic patients who improve with administration of neuroleptic drugs but not in patients who fail to display a treatment response. Twenty schizophrenic men who remained drug free for at least 2 weeks were treated with 20 mg/d of haloperidol for 5 weeks. Symptoms and plasma homovanillic acid concentrations were assessed on the last drug-free day and weekly for 5 weeks. Mean plasma homovanillic acid concentrations decreased in the group of patients who responded to neuroleptic treatment and did not change in the group of patients who did not improve. These findings suggest that there may be a qualitative distinction between responders and nonresponders to dopamine antagonists. PMID- 1929761 TI - Carbamazepine compared with lithium in the treatment of mania. AB - Fifty-two hospitalized manic patients were randomized to treatment with either carbamazepine or lithium carbonate after a 2-week drug withdrawal period. All of the probands were tertiary referrals with a high proportion of failures of previous lithium and other treatment. Weekly ratings of manic, depressive, and psychotic symptoms were obtained for 8 weeks, and responders were followed up for up to 2 years. One third of patients responded favorably. Double-blind assessments revealed no statistically reliable differences between the two treatment groups. Patients receiving carbamazepine were somewhat more manageable than patients treated with lithium early in the study, whereas lithium-treated patients remained longer in the follow-up phase. However, numbers of long-term survivors were too small to be conclusive. This study adds to the growing body of evidence that acutely manic patients respond as well to carbamazepine as to lithium. However, monotherapy with either drug is not sufficient for the majority of manic patients who are referred for tertiary care. PMID- 1929762 TI - A double-blind desipramine substitution during long-term clomipramine treatment in children and adolescents with obsessive-compulsive disorder. AB - Twenty-six children and adolescents with severe primary obsessive-compulsive disorder receiving long-term clomipramine hydrochloride maintenance treatment (mean +/- SD, 17.1 +/- 8.3 months; range, 4 to 32 months) entered an 8-month double-blind desipramine hydrochloride substitution study to assess the necessity of continued drug treatment. All patients received clomipramine for the first 3 months, then half continued with clomipramine therapy (nonsubstituted group) and half had desipramine blindly substituted for the next 2 months; all subjects again received clomipramine for the last 3 study months. Eight (89%) of nine of the substituted and only two (18%) of 11 of the nonsubstituted group subjects relapsed during the 2-month comparison period. Long-term clomipramine treatment seems necessary for this population of children and adolescents with obsessive compulsive disorder. However, even patients receiving maintenance clomipramine treatment throughout the entire study had continued obsessive-compulsive symptoms, which varied in severity over time. PMID- 1929763 TI - Anxiety disorders in children and their families. AB - The first- and second-degree relatives of children with anxiety disorders were compared with relatives of children with attention deficit-hyperactivity disorder and children who had never been psychiatrically ill for lifetime rates of psychopathological conditions, particularly anxiety disorders. Results from blind, diagnostic interviews indicated an increased prevalence of anxiety disorders in the first-degree relatives of children with anxiety disorder compared with relatives of both children with attention deficit-hyperactivity disorder and never psychiatrically ill children. Relationships between specific anxiety disorders in children and their relatives revealed an increased rate of panic disorder among the first-degree relatives of children with over-anxious disorder, compared with the relatives of children with separation anxiety disorder and children with other types of anxiety disorders. There also was a trend for panic disorder to be more prevalent among relatives of children with panic disorder than among relatives of children with anxiety disorder without panic. Obsessive-compulsive disorder was the only other anxiety disorder that appeared to show a similar specific relationship between children and their relatives. In general, the findings from this study suggest that there is a familial component involved in the pathogenesis of childhood anxiety disorders. The specificity of this relationship varies among individual anxiety disorders. PMID- 1929765 TI - Transference interpretations, therapeutic alliance, and outcome in short-term individual psychotherapy. AB - Relationships between the proportion of transference interpretations provided by therapists and both therapeutic alliance and therapy outcome were investigated for a sample of 64 patients who had received approximately 20 sessions of short term individual psychotherapy within a controlled, clinical trial investigation. Inverse relationships were found between the proportion of transference interpretations and both therapeutic alliance and favorable therapy outcome for patients with a history of high quality of object relations. An examination of individual sessions revealed evidence that was consistent with two different, but not mutually exclusive, causal explanations. The first concerned the negative effects of high proportions of transference interpretations; the second concerned the reaction of the therapist to the presence of a weak therapeutic alliance. While the evidence from our study was correlational, it was sufficiently strong to warrant alerting clinicians to the possibility of negative treatment effects when high levels of transference interpretations are used with certain types of patients receiving short-term individual psychotherapy. PMID- 1929764 TI - Cognitive-behavioral and pharmacological treatments of social phobia. A controlled study. AB - Sixty-five patients with social phobia were treated in a study that compared a cognitive-behavioral group treatment program with pharmacotherapy with alprazolam, phenelzine sulfate, or pill-placebo plus instructions for self directed exposure to phobic stimuli. Statistically significant repeated-measures effects were shown on all measures, indicating that the treatments studied were associated with substantial improvements in patients with severe and chronic social phobia. Patients who were treated with phenelzine were rated by clinicians as more improved on a measure of work and social disability than patients who were treated with alprazolam or placebo (patients in the cognitive-behavior therapy group were not rated on this measure). Subjects showed positive cognitive changes from before to after treatment, and there were no differences between treatment groups on the cognitive measure. We discuss the implications of these findings within the context of demographic and clinical predictors of response. PMID- 1929766 TI - Transient hypochondriasis: a new somatoform diagnosis? PMID- 1929767 TI - Evidence of reduced temporolimbic structure volumes in schizophrenia. PMID- 1929768 TI - Comparing age at onset of major depression and other psychiatric disorders by birth cohorts in five US community populations. AB - Using data collected in the National Institute of Mental Health (Rockville, Md) Epidemiologic Catchment Area Program, we examined the proposed hypothesis that there has been a shift in major depression to younger ages at onset, or increased prevalence in younger age periods, for recent birth cohorts. Life-table survival methods were used to examine the hazard rates for major depression as well as for other specific mental disorders. The findings are consistent with a gradual shift to increased rates for major depression between the ages of 15 and 19 years for Epidemiologic Catchment Area respondents born more recently. The findings also suggest a similar shift for drug abuse/dependence; similar but less pronounced changes were found for alcohol abuse/dependence and obsessive-compulsive disorder. However, in this study, bipolar disorder, panic disorder, and phobias did not exhibit a consistent increase in onset at younger ages. Further research is required to determine if the shifts in major depression, drug abuse/dependence, and possibly alcohol abuse/dependence are linked. It is important to note that these shifts to adolescent onset are occurring when nearly half the 31 million Americans without health insurance are aged 24 years or younger. PMID- 1929769 TI - The definition and operational criteria for treatment outcome of major depressive disorder. A review of the current research literature. AB - A review of research articles published in nine journals over a 2-year period was conducted to determine how critical changes in the clinical course of depressive disorder are defined in the research literature. These change points, labeled by terms such as response, recovery, and relapse, are critical for evaluation and communication of study results. The review focused on studies of unipolar depression that used a criterion-based diagnostic system and involved some form of therapeutic maneuver. The review showed significant inconsistency in the labeling and definition of change points and indicated the need for more precise conceptual definitions and operational criteria to enhance comparison, generalization, and application of results from clinical studies of depression. PMID- 1929770 TI - Prospective study of postpartum blues. Biologic and psychosocial factors. AB - Potential biologic and psychosocial causative factors for the postpartum blues were tested in a prospective study of 182 women followed up from the second trimester of pregnancy until postpartum week 9. Personal and family history of depression, depressive symptoms, stressful life events, and social adjustment were all assessed during the second trimester. Levels of progesterone, prolactin, estradiol, free and total estriol, and free and total cortisol were measured on several occasions during late pregnancy and early puerperium. Obstetric and child care stressors and the postpartum blues were assessed after delivery. Predictors of the postpartum blues were personal and family history of depression, social adjustment, stressful life events, and levels of free and total estriol. Our results support the hypothesis that the postpartum blues is within the spectrum of affective disorders. PMID- 1929771 TI - Independent assessment of manic and depressive symptoms by self-rating. Scale characteristics and implications for the study of mania. AB - We report the reliability and validity of the Internal State Scale, a self-report instrument for the simultaneous assessment of severity of manic and depressive symptoms. The Internal State Scale consists of four empirically derived subscales: Activation, Well-Being, Perceived Conflict, and the Depression Index. All subscales had good internal consistency reliability. Activation subscale scores were significantly higher in manic patients than in depressed patients or control subjects, while Well-Being subscale scores were significantly lower and the Depression Index subscale scores were significantly higher in depressed patients than in the other two groups. Activation subscale scores were correlated specifically with clinician ratings of mania. Depression Index subscale scores were correlated specifically with clinician ratings of depression. Further evidence for the validity of the subscales of the Internal State Scale in reflecting manic or depressive symptoms came from discriminant function analysis in which these subscales assigned 88% of subjects to the correct diagnostic groups. In affectively ill patients who were studied in two or more mood states, Activation, Depression Index, and Well-Being subscale scores changed significantly in the predicted directions, while the same discriminant algorithm assigned 79% of mood states to the correct diagnostic category. Bimodal distribution of scores of manic patients on the Well-Being and Depression Index subscales substantiated earlier findings that euphoric mood is not an essential feature of mania. Based on findings from this and previous studies, the hypothesis is proposed that variables related to activation level, and not to mood state, constitute the core characteristics of the manic syndrome. PMID- 1929772 TI - A double-blind comparison of clomipramine and desipramine treatment of severe onychophagia (nail biting). AB - Twenty-five adult subjects with severe morbid onychophagia (nail biting) and no history of obsessive-compulsive disorder were enrolled in a 10-week double-blind cross-over trial of clomipramine hydrochloride and desipramine hydrochloride. For the 14 subjects who completed the study, clomipramine hydrochloride (mean +/- SD dose, 120 +/- 48 mg/d) was superior to desipramine hydrochloride (mean +/- SD dose, 135 +/- 53 mg/d) in decreasing nail biting as measured by a repeated measures analysis of variance on the Nail Biting Severity, Nailbiting Impairment, and Clinical Progress scales. The high dropout rate at every stage of the study was in sharp contrast to that seen with psychiatric populations. From a neuroethologic perspective, similar biologic systems are hypothesized to mediate a spectrum of grooming behaviors, including onychophagia, trichotillomania, and obsessive-compulsive disorder. PMID- 1929773 TI - Regional cerebral glucose metabolism of women with trichotillomania. AB - Positron emission tomography and 18-F-fluorodeoxyglucose were used to study resting cerebral glucose metabolism in 10 adult women with trichotillomania and 20 age-matched female controls. As a group, the patients with trichotillomania showed significantly increased global (mean gray matter) and normalized right and left cerebellar and right superior parietal glucose metabolic rates. Contrary to expectation, this pattern differed from that seen in our previous investigation of obsessive-compulsive disorder. Clomipramine hydrochloride-induced improvement was negatively correlated with anterior cingulate and orbital frontal metabolism, of particular interest because similar results had been obtained for obsessive compulsive disorder. PMID- 1929774 TI - Mental disorders in adolescent suicide. DSM-III-R axes I and II diagnoses in suicides among 13- to 19-year-olds in Finland. AB - The prevalence of mental disorders (DSM-III-R Axes I and II) among adolescent suicide victims (n = 53) was investigated in a nationwide psychological autopsy study in Finland. The data were collected comprehensively through interviews of the victims' relatives and attending health care personnel and from official records. Following independent assessment by two psychiatrists, the DSM-III-R diagnoses were assigned in consensus meetings. A large majority of the victims (94%) suffered from a mental disorder. The most prevalent disorders were depressive disorders (51%) and alcohol abuse or dependence (26%). The prevalence of adjustment disorders (21%) was higher than in most studies from other countries. Personality disorder was diagnosed in 32% of the cases. Comorbidity was found in 51% of the victims. The results indicate a strong relatedness between adolescent suicide and the presence of depression, antisocial behavior, and alcohol abuse. PMID- 1929775 TI - Temporal and hippocampal metabolic rate during an olfactory memory task assessed by positron emission tomography in patients with dementia of the Alzheimer type and controls. Preliminary studies. AB - Positron emission tomography with fludeoxyglucose F 18 was used to assess cortical metabolic rate during an olfactory memory task in six patients with dementia of the Alzheimer type. Metabolic activity was compared with that of both age-matched controls performing the olfactory task and controls resting with their eyes closed. Patients had lower metabolic rates in the anterior portion of the medial-temporal cortex than did controls, and the difference was greatest between patients and the controls performing the memory task. This region is known to receive a large olfactory input and has been implicated in the encoding of human memory. Normal controls resting with their eyes closed had significantly lower metabolic rates in this area when compared with normal controls performing the task. Our results are consistent with those of earlier reports of temporal lobe decreases in metabolic rate and extend them through the examination of areas salient to the behavioral loss. PMID- 1929776 TI - Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. AB - In 1988, the MacArthur Foundation Research Network on the Psychobiology of Depression convened a task force to examine the ways in which change points in the course of depressive illness had been described and the extent to which inconsistency in these descriptions might be impeding research on this disorder. We found considerable inconsistency across and even within research reports and concluded that research on depressive illness would be well served by greater consistency in the definition change points in the course of illness. We propose an internally consistent, empirically defined conceptual scheme for the terms remission, recovery, relapse, and recurrence. In addition, we propose tentative operational criteria for each term. Finally, we discuss ways to assess the usefulness of such operational criteria through reanalysis of existing data and the design and conduct of new experiments. PMID- 1929777 TI - Compulsive feather picking in birds. PMID- 1929778 TI - Are effective antiobsessional drugs interchangeable? PMID- 1929779 TI - Follow-up study of patients with panic disorder. PMID- 1929780 TI - Gold-associated lymphadenopathy in a patient with rheumatoid arthritis. PMID- 1929781 TI - Fatal fecal embolization. PMID- 1929782 TI - Silicone in gold-associated lymphadenopathy. PMID- 1929783 TI - Laboratory phlebotomy. College of American Pathologists Q-Probe study of patient satisfaction and complications in 23,783 patients. AB - Outpatients from 630 institutions participated in a phlebotomy module of Q Probes, a quality assurance program of the College of American Pathologists, Northfield, Ill. This module assessed patient outcome measurements of complications, discomfort, and satisfaction with the phlebotomy procedure. Of the 29,700 ostensibly healthy individuals registered, 80.1% returned postcards containing measurements and assessments they made about the procedure and information recorded by the phlebotomist. The median time required for phlebotomy was 6 minutes, with 25% of patients requiring less than 5 minutes and 10% more than 21 minutes for completion of the procedure. The average number of phlebotomy attempts per patient was 1.03, with 95 patients (0.4%) experiencing three to 11 attempts. Ecchymoses occurred in 4048 (16.6%) attempts, with the median size of ecchymosis being 15.1 mm. On the average, an outstanding employee was identified by patients 46.6% of the time. The discomfort caused by the needle puncture was more than expected by 35.3% of patients. Although 98.6% of the patients were satisfied, 336 patients were dissatisfied with the procedure. We conclude that the technical skills of phlebotomists and patient satisfaction with phlebotomy are outstanding, but that patient discomfort from the procedure needs to be minimized. PMID- 1929784 TI - Cell cycle kinetic studies in human cancers. Development of three DNA-specific labels in three decades. AB - Controversy has epitomized the prognostic and clinical significance accorded to cell cycle kinetic studies in neoplastic diseases. Recent introduction of monoclonal antibodies to thymidine analogues such as iododeoxyuridine and bromodeoxyuridine has unveiled a spectacular new area of research. Large numbers of patients with liquid and solid tumors have been interrogated by introducing iododeoxyuridine and bromodeoxyuridine as DNA-specific probes in vivo. Further in vitro incubation of S-phase cells already double-labeled in vivo with tritiated thymidine has added a whole new dimension to the kinds of questions that can now be addressed with alacrity. Time is rapidly approaching when this information will be available in a prompt enough fashion to be useful for planning therapeutic strategies. Reviewed are the salient features of the rapid progress achieved in the last decade in this exciting discipline. PMID- 1929785 TI - Differential expression of c-myc and H-ras oncogenes in Barrett's epithelium. A study using colorimetric in situ hybridization. AB - To determine the role of c-myc and H-ras in progressive, dysplastic Barrett's mucosa (BM), and the usefulness of these oncogenes as markers for dysplastic lesions at high risk for malignant transformation, sequential formaldehyde solution-fixed, paraffin-embedded biopsy specimens that were obtained from 12 patients with BM were evaluated by in situ hybridization with the use of biotinylated complimentary DNA probes. Nine of the patients were taken from a previous prospective study. Four of these nine patients had dysplasia, and adenocarcinoma had developed in two of them; five had nondysplastic BM only. Two additional patients had adenocarcinoma, but their initial biopsy specimens had revealed dysplasia. One additional patient had intermediate-grade dysplasia. The intensity of oncogene expression was quantified by computerized color-image analysis. Enhanced c-myc expression of approximately equal intensity was consistently observed in all grades of dysplasia and carcinoma. H-ras was also consistently expressed in higher grades of dysplasia and carcinoma but not in low grade dysplasia. Neither c-myc nor H-ras expression was detected in nondysplastic BM. The expression of H-ras in dysplastic BM appears to be a helpful marker for identifying which dysplastic lesions will progress to carcinoma. PMID- 1929786 TI - Emerging patterns of cocaine use and the epidemic of cocaine overdose deaths in Dade County, Florida. AB - With the increasing use of cocaine in the United States, cocaine overdose deaths are being reported with increasing frequency. To describe patterns of cocaine use involved in cocaine overdose deaths, we reviewed the postmortem records from the Metropolitan Dade County Medical Examiner Department, Miami, Fla. We identified 239 cocaine overdose deaths from 1971 through 1987. During this period, the incidence of cocaine overdose deaths increased 20-fold, with the largest proportional increases occurring among persons aged older than 24 years, white persons, and men. The percentage of deaths that involved use of cocaine by nonparenteral routes, as well as newer and unknown preparations of cocaine (such as "crack" and "free-base" cocaine), increased. For example, the percentage of deaths that involved use of crack or free-base cocaine increased from 8% in 1981 to 20% in 1987. Persons who died after smoking crack or free-base cocaine had lower blood cocaine levels at autopsy (median level, 0.3 mg/L) than persons who died as a result of using cocaine hydrochloride (median level, 3.7 mg/L). Patterns of cocaine use involved in the epidemic of cocaine overdose deaths are changing. The data suggest that the newer preparations of cocaine, such as crack or free-base cocaine are playing an increasingly important role in this epidemic and that these preparations may be more toxic than cocaine hydrochloride. PMID- 1929787 TI - Well-differentiated extraskeletal osteosarcoma. A soft-tissue homologue of parosteal osteosarcoma. AB - We describe a unique case of a low-grade extraskeletal osteosarcoma revealing both histologic and radiologic features reminiscent of parosteal osteosarcoma. The tumor, which had been present for 10 years, occurred in the left axilla of a 74-year-old black woman. To date, all the published cases of extraskeletal osteosarcoma have been high-grade neoplasms; to our knowledge, this is the first reported case of a low-grade extraskeletal osteosarcoma. PMID- 1929788 TI - Malignant melanoma of the hepatic and common bile ducts. A case report and review of the literature. AB - We report a case of malignant melanotic melanoma involving the extrahepatic biliary tract in a 34-year-old white woman. The diagnosis was established using conventional light microscopic examination and immunohistochemical stains. The clinical absence of any primary cutaneous or visceral melanoma suggests that the tumor arose primarily from the biliary tract. To our knowledge, only two previous cases of malignant melanoma of the common bile duct have been reported in the literature. PMID- 1929789 TI - Neutrophils in chronic active hepatitis type B. AB - Liver biopsy specimens from 95 patients with chronic active hepatitis type B were studied to define the incidence of portal tract and/or septal neutrophilic infiltration and its relationship with other morphohistologic factors and with liver function tests. Neutrophils were identified in the portal tracts and fibrous septa in 59 cases (62%), among which 19 cases (20%) showed four or more neutrophils per high-power field. Significant neutrophilic infiltration (greater than 6 per high-power field) was observed in only seven (7.4%) of 95 cases. Multiple-regression analysis revealed that neutrophilic infiltration was significantly associated with marginal duct proliferation, bile duct proliferation, and an elevated alanine aminotransferase level. Applying a partial correlation coefficient, it was shown that neutrophilic infiltration was not related to piecemeal necrosis after controlling for marginal duct proliferation or bile duct proliferation. The findings suggest that in chronic active hepatitis B, while piecemeal necrosis interferes with bile flow at the limiting plate region, marginal duct and bile duct proliferations follow and lead to the accumulation of neutrophils. PMID- 1929790 TI - Congenital granular cell tumor with systemic involvement. Immunohistochemical and ultrastructural study. AB - We present an autopsy case of a 29-week-old male fetus with a very unusual set of congenital granular cell tumors, including gingival epulis and granular cell lesions of the kidneys, lung, heart, esophagus, small and large intestine, thyroid, adrenals, spleen, urinary bladder, testis, pituitary, and leptomeninges. The granular cells were distributed mainly through the stroma of the organs, but they also involved the epithelial lining of the seminiferous and renal tubules. Ultrastructurally, the gingival, pulmonary, and renal tumors were basically the same in appearance as membrane-bound heterogeneous bodies. Immunohistochemical studies were negative for S100 protein, lysozyme, alpha 1-antitrypsin, cytokeratin, and vimentin in the gingival mass as well as in other systemic lesions. The immunohistochemical reaction pattern of the granular cells in our case was more like the cells of the congenital granular cell epulis rather than adult granular cell tumor because of its negative reaction to S100 protein. However, the involvement pattern was that of the adult form of granular cell tumor. Several developmentally different cells, such as renal tubular epithelial cells, seminiferous tubular cells, gingival stromal cells, and parenchymal cells of many organs, were involved in this granular cell process. The myofibroblastlike cells seen in the region of segmental dysplasia of the kidney showed the same cytoplasmic material as in typical granular cells. Based on these findings, it is suggested that a histogenesis of multiple cell origin of the granular cell tumor could be strongly supported. PMID- 1929791 TI - Primary ovarian leiomyosarcoma. An immunohistochemical and ultrastructural study. AB - Primary sarcoma of the ovary is rare, and only 16 reported examples of leiomyosarcoma are known to us. We encountered a primary ovarian leiomyosarcoma in a 58-year-old woman. The tumor was characterized by interlacing bundles of plump spindle cells that showed immunoreactivity for desmin, vimentin, and muscle specific actin. Ultrastructural features included abundant smooth-muscle-type filaments, notched nuclei, pinocytotic vesicles, and extracellular collagen. This case illustrates the utility of ancillary techniques in the classification of pure ovarian sarcomas and leads us to propose ultrastructural and immunohistochemical criteria for primary ovarian leiomyosarcoma. PMID- 1929792 TI - Adventitial cystic disease of the lesser saphenous vein. AB - Adventitial cystic disease or degeneration of the blood vessel wall is an unusual form of peripheral vascular disease that occurs almost exclusively in the popliteal artery and accounts for an estimated one in 1200 cases of claudication. The cause of adventitial cystic disease is unknown, but it has been attributed to repeated trauma, an ectopic ganglion, or primary dysplasia of the vascular connective tissue. We describe an unusual case of adventitial cystic disease of the lesser saphenous vein located adjacent to the ankle joint. Only a handful of cases of venous adventitial cystic disease have been reported in the English literature, and, to our knowledge, none involved the lesser saphenous vein. PMID- 1929793 TI - Immunoglobulin-related amyloidosis presenting as recurrent isolated lymph node involvement. AB - Up to 37% of cases of generalized primary and secondary amyloidosis demonstrate lymph node involvement. Lymph node involvement as the presenting feature of generalized amyloidosis is uncommon. Isolated lymph node amyloidosis (that is, with no extranodal amyloidosis) is exceedingly rare; review of the literature reveals only two reported cases. A case of recurrent isolated lymph node amyloidosis is presented, with review of the literature. PMID- 1929794 TI - Multifocal malignant melanoma arising in vesicovaginal melanosis. AB - An 80-year-old white woman developed vulvar melanosis and malignant melanoma of the labia majora and clitoris and underwent a simple vulvectomy. She subsequently developed melanosis of the urinary bladder and presented 3 years later with multifocal malignant melanoma involving the vagina, urethra, and urinary bladder in a background of extensive melanosis with variable degrees of atypia. She underwent radical surgery but died 18 months later with liver metastases and liver failure. Malignant melanoma is uncommon in the vulva and vagina and is rare in the urinary bladder. This case illustrates the previously described association between melanosis and malignant melanoma. The unusual features are the widespread distribution of the melanosis (vagina and bladder) and the subsequent development of multifocal malignant melanoma. PMID- 1929795 TI - Paneth-like cells in an adenoma and adenocarcinoma in the ampulla of Vater. AB - A case of adenocarcinoma with significant Paneth cell differentiation arising in a villoglandular polyp at the ampulla of Vater is presented. Paneth-like cells, containing distinct fuchsinophilic granules, were a prominent component of the nonglandular invasive adenocarcinoma and were also seen in the associated adenomatous polyp. Lysozyme, trichrome, and periodic acid-Schiff digest stains, and electron microscopy confirmed that the granules were lysosomal in nature. This case confirms that cells with Paneth-like features can be a significant component in invasive neoplasms and can occur at unusual sites such as the ampulla of Vater. PMID- 1929796 TI - Postpoliomyelitis muscle weakness: a prospective study of quadriceps strength. AB - The objective of this study was to evaluate the presence of progressive postpoliomyelitis muscle weakness (PPMW) in affected individuals 20 to 40 years after the initial polio infection. Over a three-year period, the isometric and isokinetic strength of the quadriceps femoris muscle was studied in seven symptomatic patients with previous poliomyelitis (mean = 38.3 years from infection) to determine if quadriceps strength decreased during the three years. Each patient had a quadriceps affected by polio on one side and a clinically nonaffected quadriceps on the contralateral limb. The maximal isometric force and the peak isokinetic force of the affected quadriceps (AQ) and nonaffected quadriceps (NQ) muscles were tested on a computerized isokinetic dynamometer machine at six-month intervals. Isometric force increased significantly, by 29% per year (p less than .02) in the AQ and by 14% per year (p less than .05) in the NQ. Paired analysis to determine the change in strength between the affected and nonaffected muscles for the isometric data showed a mean nonsignificant increase in the AQ of 14% per year (p = .01). The change in peak isokinetic force demonstrated a significant increase in the AQ of 35% per year (p less than .05); whereas, the NQ peak isokinetic force increased 15% per year which was not statistically significant. Paired analysis to determine the change in strength between the affected and nonaffected muscles for the isokinetic data showed a nonsignificant relative increase in the AQ of 20% per year (p less than .06).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929797 TI - Electrophysiologic evaluation of local steroid injection in carpal tunnel syndrome. AB - Extensive sensory and motor nerve conduction studies were performed in a series of patients with electrophysiologically proven, idiopathic carpal tunnel syndrome who were treated by a single steroid injection (40 mg of triamcinolone acetonide). Electrophysiologic studies, which included evaluation of median, ulnar, and radial orthodromic sensory action potentials, median and ulnar motor action potentials, and electromyography of two intrinsic muscles of the hand, were done before and at 45 days and six months after the treatment. By the end of the follow-up period, the symptoms had remitted completely in 11 hands (35%), 18 (58%) benefitted from partial relief, and two did not improve. In addition to the relief of symptoms, abnormalities of motor nerve conduction improved in 65% of cases, and abnormalities of sensory nerve conduction improved in 73% of all the individual digital branches of the median nerve examined. Recovery of function of the median nerve continued for a long period, even after the pharmacologic effect of the steroid agent had presumably ceased. PMID- 1929798 TI - Persistent hypertension in young spinal cord injured individuals resulting from aortic repair. AB - The development of persistent hypertension in young, previously healthy paraplegic individuals is unusual; it could be postulated that hypertension is a cardiovascular response peculiar to patients who sustained spinal cord injury after surgical repair of the aorta with trauma-related injuries. In a retrospective study of 712 patients sustaining spinal cord injury during the last decade, seven sustained paraplegia after aortic repair that was necessitated by trauma-related injuries. Despite the low incidence of new-onset hypertension in paraplegic patients, five of the seven developed hypertension, of which three required chronic antihypertensive medications. It is well documented that patients with lesions of the neuraxis above the sixth thoracic segment are prone to the phenomenon of autonomic hyperreflexia. This results from interruption of the baroreceptor reflex and the descending tracts of the spinal cord. There is evidence that the renin-angiotensin system, catecholamines, and receptor-site activity play an important role in the control of blood pressure in spinal cord injured patients. Additional investigation of this rare subgroup of spinal cord injured patients may further illuminate the effect of spinal cord injury on autonomic control of the cardiovascular system. PMID- 1929799 TI - Infertility in men with spinal cord injury. AB - Infertility is a significant and frustrating problem for many men after spinal cord injury. The two major causes are poor semen quality and ejaculatory dysfunction. Factors attributed to poor semen quality include stasis of prostatic fluid, testicular hyperthermia, recurrent urinary tract infections, abnormal testicular histology, possible changes in the hypothalamic-pituitary-testicular axis, possible sperm antibodies, chronic long-term use of various medications, and type of bladder management. Further work is needed to define the impact and importance of each of these factors. Ejaculations are reported to occur in only 5% of men with spinal cord injury (SCI) who have complete upper motor lesions and 18% of those who have complete lower motor lesions. Ejaculations occur in up to 70% of men with incomplete lesions. Methods that have been used to induce an ejaculate include intrathecal neostigmine, subcutaneous physostigmine, direct aspiration of sperm from the vas deferens, vibratory stimulation, electroejaculation, and direct stimulation of the hypogastric nerve. The most commonly used methods in the United States are electroejaculation and vibratory stimulation; using these two methods, ejaculates can be obtained up to 85% and 59% of the time, respectively. Each of these methods has advantages and disadvantages. Particular care needs to be given to monitoring men undergoing these procedures who are prone to autonomic dysreflexia. The future outlook is encouraging once improved technology for obtaining semen and various methods to assist reproduction, such as in vitro fertilization, are available. PMID- 1929800 TI - Intractable muscle pain syndrome, osteomalacia, and axonopathy in long-term use of phenytoin. AB - Muscle pain syndrome is a complicated situation in that even an extensive work-up may overlook the primary etiology. A patient with multiple medical problems, including a history of partial gastrectomy due to trauma, a below-knee amputation from arteriosclerotic disease, and chronic phenytoin therapy for a seizure disorder, developed intractable, generalized muscle pain, with total dependency in mobility and self care. He was admitted to an acute care hospital and was eventually discharged with a diagnosis of occult malignancy. After being referred to our amputee clinic for prosthetic management, the patient was admitted for inpatient rehabilitation. Electrodiagnostic studies and muscle biopsy revealed typical neuropathic findings and nonspecific myopathic changes. Laboratory studies showed a vitamin D deficiency with secondary hyperparathyroidism. Discontinuation of phenytoin and treatment with calcium and vitamin D resulted in rapid relief of muscle pain and marked improvement in mobility and self care. This case illustrates an unusual combination of phenytoin-induced axonopathy and osteomalacia that incapacitated an otherwise functional person with below-knee amputation. PMID- 1929801 TI - Rehabilitation of neurologic disability related to human immunodeficiency virus. AB - Acquired immunodeficiency syndrome (AIDS) is globally fatal; before death, it often causes a multitude of medical complications leading to significant physical impairment and functional loss. Specifically, the neuropathology associated with AIDS can be diverse, and it ranges from inconsequential cerebrovascular insults to rapidly progressive neuronosis. Moreover, physical impairments may present any time during the course of the disease and even before knowledge of seropositivity. We present three patients infected with human immunodeficiency virus (HIV), each with a different form of neuropathology, who were treated by rehabilitative services and who gained reasonable functional benefits within moderate time periods. The growing number of HIV-infected persons with physical debilitation mandates a rational, knowledgeable approach to rehabilitation intervention. This article highlights the importance of a thorough understanding of the neurologic complications of AIDS in setting realistic goals and in improving the quality of life for these individuals. PMID- 1929802 TI - Acute stroke patients: long-term effects of rehabilitation and maintenance of gains. AB - The efficacy of rehabilitation programs to facilitate recovery after acute stroke remains controversial. To further evaluate this issue, the records of 139 "middle band" stroke survivors were reviewed retrospectively at admission to, discharge from, and one-year follow-up from inpatient rehabilitation. Patients were divided into two groups (out-patient [O/P] or no O/P) based on their involvement in physical and occupational therapy services. A repeated measures ANOVA indicated that both groups made clinically and statistically significant improvements in all functional indices between stroke onset, discharge from inpatient rehabilitation, and follow-up: O/P therapy: mobility F(1,46) = 1651, p less than .0001; self-care F(1,47) = 1062, p less than .0001; total F (1,47) = 1093, p less than .0001; no O/P therapy: mobility F(91,88) = 5643, p less than .0001; self care F(1,88) = 5722, p less than .0001; total F(1,88) = 6733, p less than .0001. Pairwise comparisons for all functional indices revealed that all statistically significant changes in function in the no O/P therapy group occurred between stroke onset and discharge: self-care (p less than .0001), mobility (p less than .0001), and total (p less than .0001). Pairwise comparisons of all indices in the O/P therapy group revealed that all differences between stroke onset and discharge functional scores were at the p less than .0001 level, and score differences between discharge from inpatient rehabilitation and follow-up were as follows: self-care (p less than .05), mobility (p less than .001), and total (p less than .005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929803 TI - Elements of academic productivity: a comparison of PM&R units versus other clinical science units. AB - In early 1989, the Research Committee of the American Academy of Physical Medicine and Rehabilitation (AAPM&R) established a subcommittee to develop methods to monitor academic progress in physical medicine and rehabilitation (PM&R) units in the US. To develop an indirect baseline of academic productivity in PM&R, the rates and types of publications by PM&R researchers were assessed in eight peer review medical journals. The journals selected consisted of all issues of the following (published in calendar years 1987 to 1989): Archives of Physical Medicine and Rehabilitation, American Journal of Physical Medicine and Rehabilitation, Physical Therapy, Archives of Neurology, Pain, Stroke, Paraplegia, and Arthritis & Rheumatism. The sampling frame consisted of 3,553 journal articles. Affiliation with a PM&R unit or other clinical science unit (other unit), extramural funding sources, and type of manuscript (eg, case report or scientific investigation) were identified and coded. Sixteen percent of all articles were authored by members of PM&R units. The prevalence of scientific reports written by other unit authors (71%) was comparable to that written by PM&R authors (67%) (chi 2[3] = 5.54; p less than .20). There was a greater prevalence of funding by the US Department of Education of studies written by PM&R authors (10%) than of studies written by members of other units (2%) (chi 2[1] = 79.4; p less than .0001). Reports authored by members of other units had a greater prevalence rate of funding from all other sources--federal and private (47% vs 33%; chi 2[1] = 41.2; p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929804 TI - Assessment of total head excursion and resting head posture. AB - Clinicians typically evaluate head posture and cervical range of motion in both standing and sitting positions. There are currently few quantitative data available regarding resting head posture (RHP) or total head excursion (THE), a retraction-protraction gliding range of head motion in the sagittal plane, and where the RHP lies within THE. The purposes of this study were to describe quick and simple methods to determine quantitative measurements of THE, RHP while sitting, and RHP while standing, to provide preliminary data on these postural measurements for men and women in four age categories; and to determine the effects of gender and age on these measurements. Subjects included 218 able bodied adults. Measurements of THE, RHP while sitting, and RHP while standing were taken. A two-way multivariate analysis of variance followed by two-way analyses of variance showed only the main effect of gender to be significant (p less than .05) for each of the dependent measurements. Across the age groups, men had a greater excursion distance from retraction to protraction than women. Within THE, women held their heads more forward than men. Men held their heads farther from the vertical than women while standing. These results indicate that normal head and neck posture is different for men and women and should not be judged by the same standard. The methods used in this study are clinically advantageous in that they produce objective, quantitative measurements of THE and RHP that may be obtained quickly and with minimal equipment. PMID- 1929805 TI - Speed variation and resultant joint torques during sit-to-stand. AB - The purpose of this study was to test the hypothesis that a progressively faster speed of ascent requires significantly greater peak resultant joint torque (RJT) at major load-bearing joints of the lower limb during the sit-to-stand (STS) transfer. Eight healthy adults performed the STS at slow, natural, and fast speeds. A motion analysis system and two force platforms were employed to record kinetic data, and equations of motion were applied to compute the RJT for the ankle, knee, and hip. The results of the study supported the hypothesis that when the speed of ascent increased progressively, the peak hip flexion, knee extension, and ankle dorsiflexion RJTs increased disproportionately. However, the peak hip extension and ankle plantar flexion RJTs remained relatively constant across the range of the speeds. Implications for clinical practice pertaining to the timing and magnitude of RJT, as well as for interventions that emphasize the adaptive characteristics of movements, are suggested. PMID- 1929806 TI - A portable, easily performed muscle power test and its association with falls by elderly persoms. AB - This study developed and evaluated a simple, inexpensive, and safe screening test for assessment of falling risk in elderly persons. Subjects sat in chairs (hips and knees at 90 degrees) with their feet over a force transducer and stood as forcefully as possible. After standing for five seconds, they sat as fast as possible. The rate of change in force (dF/dT) for standing and sitting were calculated from data collected by computer. A group of nonfallers (n = 23, age = 23 to 72 years) and a group of fallers (n = 22, age = 63 to 92 years) were studied. Nonfallers' dF/dT for standing decreased linearly from 4kg.sec-1.kg-1 to 2.5kg.sec-1.kg-1. Values in fallers decreased linearly from 3kg.sec-1.kg-1 to 0.1kg.sec-1.kg-1. The dF/dT for sitting was not dependent on age in either group. Fallers had lower dF/dT than nonfallers (1.3 +/- .6kg.sec-1.kg-1 and 2.3 +/- .01kg.sec-1.kg-1, respectively). Seventeen of 22 fallers were identified by a reduced dF/dT and reduced overshoot force (kg). PMID- 1929807 TI - Physiologic costs of computer-controlled walking in persons with paraplegia using a reciprocating-gait orthosis. AB - Blood pressure, heart rate, oxygen uptake, cardiac output, and the surface electromyogram from key muscle groups in the upper body were measured in four subjects with paraplegia during ambulation using only a reciprocating-gait orthosis (RGO) and using an RGO with movement assisted by functional electrical stimulation (FES) of the hamstring and gluteus maximus muscles. These data were compared to data collected on four able-bodied control subjects during ambulation at matched speeds. Whether walking with FES and RGOs or walking with RGOs alone, subjects had an optimum gait speed at which efficiency was highest. For paralyzed subjects using FES, the optimum walking speed was approximately 1.5 mph (2.4km/hr); without FES, the optimum speed averaged about 0.75mph (1.2km/hr). Blood pressure, heart rate, oxygen uptake, and cardiac output were measured during ambulation with FES and were found to be higher than those of controls, but they were significantly lower than those in the paralyzed subjects in RGOs with no FES. Electromyogram studies showed that the activity in upper body muscles was much higher when walking in RGOs without FES than in RGOs with FES. PMID- 1929808 TI - Monitoring rate of recovery to predict outcome in minimally responsive patients. AB - Existing methods of assessing neurobehavioral responsiveness in severely brain injured patients are limited by their inability to recognize subtle clinical changes over time. This study evaluates the Coma Recovery Scale (CRS), developed for use during acute rehabilitation. The CRS was designed to detect subtle changes in neurobehavioral status and to predict outcome in patients with sever alterations of consciousness. Acceptable levels of concurrent validity were established with the Disability Rating Scale ([DRS], r = -.93) and the Glasgow Coma Scale ([GCS], r = .90). The CRS was also found to have adequate interrater reliability (kappa = .83). Twenty-eight minimally responsive patients, unable to communicate or follow commands reliably, were evaluated on the CRS, the DRS, and the GCS. Although initial scores on all three scales were significantly correlated with outcome at discharge, change scores were more predictive of outcome. In addition, CRS change scores correlated higher with outcome (r = -.78, p less than .01) than DRS and GCS change scores. These findings indicate that the CRS is a sensitive measure of neurobehavioral responsiveness and suggest that rate of change during acute rehabilitation may be an important outcome predictor. PMID- 1929809 TI - Scintigraphy for the detection and quantification of subglottic aspiration: preliminary observations. AB - Eleven patients with previously documented aspiration underwent a radioisotopic swallowing study to detect and quantify airway penetration. In those subjects able to complete a rapid-acquisition phase during swallowing, no laryngotracheal penetration was seen despite previous evidence of aspiration. However, sequential static pulmonary imaging showed significant aspiration in three individuals. Attempts were made to measure the percentage of ingested material aspirated and the clearance rate from the airways. Eight patients (73%) failed to show definite evidence of aspiration on scintigrams. It is hypothesized that the lack of scintigraphic detection in previously proven aspirators was due either to interval improvement of the dysphagia or to difficult-to-detect laryngotracheal aspiration. Isotopic imaging during swallowing appears to have little utility; however, after ingestion, the technique can demonstrate more distal penetration not detected on videofluoroscopy. More studies are suggested to better define the sensitivity and specificity of scintigraphy in aspiration detection and to determine whether these techniques have prognostic value that could alter patient management. PMID- 1929810 TI - Modified sphygmomanometer versus strain gauge hand-held dynamometer. AB - The purpose of this study was to compare measurements of elbow flexor muscle strength obtained with a modified sphygmomanometer (MS) and a strain gauge hand held dynamometer (HHD). Thirty-two healthy subjects performed two isometric contractions of about five seconds against each device. Repeated measurements with each device did not differ significantly and were correlated (r greater than .960) and reliable (intraclass correlation coefficients greater than .960). The means of two measurements obtained with each device were related in a curvilinear manner (R = .882), with MS measurements above 210 mmHg rising more slowly than corresponding HHD measurements. Although supporting the reliability of each device, the results suggest that the devices do not provide comparable measurements throughout the range of the MS. The MS may not be the best choice for obtaining accurate strength measurements of stronger individuals. PMID- 1929811 TI - H-reflex modulation during manual muscle massage of human triceps surae. AB - An investigation of the effect of a six-minute manual muscle massage on the excitability of the spinal reflex pathway in 20 able-bodied subjects was undertaken. H-reflex recordings were obtained from the right soleus muscle, which was the site being massaged. Skin temperature and antagonist activity were monitored in an attempt to explain the changes observed in a previous study. The experimental paradigm chosen was an A-B-A interrupted-time series design consisting of two pretreatment, two treatment (massage), and two posttreatment conditions. H-reflex amplitudes recorded during both massage conditions (.76 +/- .58 mV, .76 +/- .61 mV) were significantly reduced (F5,90 = 69.04, p less than .01) in comparison to all other (before and after) conditions (2.58 +/- .75 mV, 2.56 +/- .71 mV, 2.82 +/- 1.14 mV, and 2.89 +/- .82 mV, respectively). This decrease could not be explained conclusively by changes in skin temperature, nerve conduction velocity, or antagonist recruitment, thus indicating a decrease in spinal reflex excitability attributed to massage. These findings also support our earlier report, which stated that H-reflex amplitudes are reduced only during the period of tissue manipulation, regardless of the duration of the massage. PMID- 1929812 TI - Pain disability index: construct and discriminant validity. AB - The Pain Disability Index (PDI) was developed as a self-report measure of general and domain-specific, pain-related disability. This study's purpose was twofold: (1) to assess construct validity of the scale relative to other measures of pain related disability and psychologic distress and (2) to assess the strength of the PDI, independent of pain intensity, in accounting for behavioral and psychologic aspects of disability. Results indicated stronger correlations for PDI factor 1 (discretionary activities) than factor 2 (obligatory activities), with factor scores significantly related to both psychologic distress and behavioral measures of disability. Partial correlation controlling for pain intensity demonstrated PDI factor 1 was significantly related to depression, employment status, and medication usage. The finding supports the usefulness of the PDI in providing important information on functional disability beyond what is provided by a simple measure of pain intensity. PMID- 1929813 TI - Late effects of polio: critical review of the literature on neuromuscular function. AB - Many individuals who have had poliomyelitis are now complaining of several new problems attributed to their former illness including muscle atrophy; fatigue; progressive weakness; and muscle, back, and joint pain. This paper critically examines the literature regarding the neuromuscular effects of poliomyelitis. Weakness resulting from poliomyelitis was due to destruction of anterior horn cells. After the illness, muscle strength was partially recovered as a result of several physiologic adaptive mechanisms including terminal sprouting and reinnervation, myofiber hypertrophy, and, possibly, myofiber type transformation. Several pathophysiologic and functional etiologies have been proposed for late neuromuscular deterioration, but none has been proven. In fact, to date, there is no objective evidence documenting progressive loss of strength in polio survivors. Studies attempting to differentiate polio survivors with and without symptoms of deterioration have resulted in conflicting results; however, it appears reasonable to conclude that symptomatic postpolio subjects had a more severe illness with greater loss of neuromuscular function. Exercise may be helpful for many postpolio patients, but the prescription must be tailored to the individual to avoid problems of overuse or excessive fatigue. PMID- 1929814 TI - Spinal cord injury syndrome with motor sparing in the absence of all sensation. AB - This paper describes the anatomic basis for the unusual presentation in a spinal cord injured subject of preservation of motor power in the absence of all sensation. The patient was examined at four hours, and daily thereafter, after a motorcycle accident in which he was thrown over the handle bars. He had trace ankle dorsi and plantar flexors, but light touch, pin, position, and vibratory sensation were absent below the level of C4 bilaterally. There was no physical evidence to differentiate whether he suffered a flexion or extension injury. Cervical spine films showed no evidence of fracture or dislocation, but anterior and posterior osteophytes involving C3 to C4, C4 to C5, and C5 to C6 were present. Magnetic resonance imaging showed evidence of cervical cord edema at C3 to C4 with possible hemorrhage and severe spinal stenosis at C3 to C4 and C4 to C5. This patient received a compression injury with resulting classic anterior spinal artery syndrome. Because of his spinal stenosis with a decreased anterior posterior (AP) diameter of the canal, the posterior circulation was also compromised. The extensive pial anastomotic network provided relative sparing of the most peripheral components of the lateral corticospinal tracts. This case report demonstrates a unique clinical picture that cannot be anatomically classified by current American Spinal Injury Association (ASIA) standards as central cord syndrome. It can be explained by the lamination of the ascending and descending tracts in relation to the vascular supply of the cervical cord in conjunction with the narrowing of the AP diameter of the canal due to spinal stenosis. PMID- 1929815 TI - Pulsed irrigation enhanced evacuation: new method for treating fecal impaction. AB - Fecal impaction is a common problem in patients with neurologic impairment. The pulsed irrigation enhanced evacuation (PIEE) procedure is a new method of clearing fecal impactions using pulses of small amounts of warm water to rehydrate stool and improve peristalsis. Thirty-seven PIEE procedures were performed on 28 patients with a variety of neurologic problems. The PIEE procedure was observed to be effective and safe. It should be a useful adjunct to a proper bowel management program. PMID- 1929816 TI - Reflections on my surgical residency. PMID- 1929817 TI - Benefits of carotid endarterectomy confirmed by randomized trial. PMID- 1929818 TI - Surgery and surgical education on the Pacific coast in the 19th century. PMID- 1929819 TI - Bile duct carcinoma in the elderly. A rationale for surgical management. AB - Recent studies have advocated the nonoperative treatment of elderly patients with bile duct cancer using biliary endoprostheses. In addition to a 30-day mortality rate of 9%, disadvantages with this approach include lack of a definitive diagnosis and the inability to assess resectability. For comparison, we reviewed 42 consecutive cases of bile duct cancer managed surgically at UCLA (from 1954 to 1988) among patients age 70 years or older. Histologic confirmation of bile duct cancer was obtained for 40 surgical patients (95%) in the series. The 30-day mortality rate was 10%. There was a trend to more aggressive surgical management during the study, with a concomitant doubling in survival rates (from 21% among patients treated between 1954 and 1978 to 53% among patients treated between 1979 and 1988 at 1 year after surgery.) We conclude that elderly patients should not be denied surgical evaluation of malignant neoplasms of the bile duct simply on the basis of age. PMID- 1929820 TI - A current analysis of primary lymphoma of the thyroid. AB - Over a 9-year period ending in May 1990, 27 patients with histologically proved thyroid lymphoma were assessed and treated. There were 24 female and three male patients with a median age of 67 years at the time of diagnosis (age range, 39 to 85 years). The usual presentation was that of a rapidly enlarging neck mass. Incisional biopsy was the diagnostic procedure of choice; however, nine of 27 patients underwent diagnostic partial or total thyroidectomy based on a preoperative impression of thyroid carcinoma. All 27 patients had non-Hodgkin's lymphomas of intermediate (77%) or high (23%) grade. Detailed staging was carried out in 25 patients; seven patients (28%) had disease confined to the thyroid gland (stage I), while 18 (73%) had accompanying disease in cervical lymph nodes or the mediastinum (stage II). Combined multiagent chemotherapy and irradiation was given to 19 of 25 staged patients (76%). Actuarial, overall 5-year survival for all patients was 70% with 48 months being the median follow-up for living patients (follow-up range, 3 to 102 months). Of a number of factors evaluated using log-rank survival tests, only the absence of dysphagia at the time of hospital admission, a primary tumor mass not greater than 10 cm, restriction of disease to the thyroid gland, and the absence of mediastinal lymph node involvement were statistically significant predictors of improved survival. Surgery should usually be restricted to diagnostic biopsy, as there is infrequently a role for resection in the management of thyroid lymphoma, given the effectiveness of combined multiagent chemotherapy and radiotherapy. PMID- 1929821 TI - Calciphylaxis in secondary hyperparathyroidism. Diagnosis and parathyroidectomy. AB - Calciphylaxis is a rare, severe complication of secondary hyperparathyroidism. Patients present with painful, violaceous, mottled skin lesions of the upper and lower extremities, which become necrotic and produce nonhealing ulcers. Gangrene of fingers and toes frequently requires amputation, produces nonhealing wounds, and can lead to sepsis and death. We reviewed the clinical course of five patients with calciphylaxis treated in our institution. The three men and two women (aged 47 to 72 years) had secondary hyperparathyroidism from chronic renal failure. All patients had severe pruritus, painful ulcers, and severe hyperphosphatemia with elevated serum calcium-phosphate product (greater than 12 mmol2/L2), but the serum parathyroid hormone levels were only moderately elevated. Most patients had medical calcification of medium and small blood vessels, and some had soft-tissue calcification visible on roentgenography. Treatment consisted of local wound care, antibiotics, phosphate-binding agents, and parathyroidectomy. Two patients died of uncontrollable sepsis. The three survivors had dramatic improvement of pain and ulcers after parathyroidectomy. Calciphylaxis is a limb- and life-threatening complication of secondary hyperparathyroidism. Diagnosis can be made by recognizing the characteristic painful skin lesions, ulcers, and gangrene of the digits, and patients should be treated with subtotal parathyroidectomy. PMID- 1929822 TI - In vivo measurement of breast cancer growth rate. AB - S-phase cells of 66 primary breast cancers were labeled in vivo by preoperative infusion of the thymidine analogue bromodeoxyuridine. A monoclonal antibody specific for DNA-incorporated bromodeoxyuridine was used to identify positive cells and compute a labeling index on histologic sections. The labeling index (the percentage of cells in S-phase) ranged from 0.1% to 23.9%; it correlated positively with poorly differentiated cancer, higher mitotic counts on routine histologic examination, and tumor size; and it correlated inversely with estrogen and progesterone receptors. The labeling index did not correlate with nodal involvement or ploidy. Of the 15 patients with a labeling index greater than 12%, three died and one had systemic disease after a median follow-up of 19 months. No other patients had recurrences. There were no clinical complications of bromodeoxyuridine infusion. PMID- 1929823 TI - Control of dumping symptoms by somatostatin analogue in patients after gastric surgery. AB - Octreotide acetate is a long-acting analogue of the naturally occurring inhibitory gastrointestinal peptide, somatostatin. We tested the efficacy of octreotide in controlling the symptoms of dumping syndrome in response to a provocative meal in a randomized, double-blinded, crossover trial in nine severely affected patients. Pretreatment with octreotide acetate (100 micrograms injected subcutaneously) reduced postprandial dumping symptoms from a mean +/- SEM score of 15.7 +/- 1.6 (placebo treatment day) to 4.6 +/- 1.7. With placebo treatment, all nine patients became symptomatic in response to the meal, whereas with octreotide treatment, symptoms occurred in only two of nine patients. Similarly, all placebo-treated patients showed a postprandial increase in pulse rate to a mean +/- SEM of 105 +/- 6 beats per minute, whereas only one of nine octreotide-treated patients showed an increase in pulse rate (mean +/- SEM, 80 +/ 3 beats per minute). These differences were also statistically significant. While no significant changes were observed in postprandial hematocrit values or osmolality between placebo and octreotide treatments, octreotide prevented hypoglycemia in four affected patients and significantly inhibited insulin release. We conclude that octreotide is a useful tool in the treatment of patients with severe, refractory dumping syndrome. PMID- 1929824 TI - Is early prediction of outcome in severe head injury possible? AB - To determine whether the outcome of patients with severe head injury could be predicted early after presentation to the hospital, the records of 306 trauma patients with head injury and Glasgow Coma Scale scores of 10 or less were reviewed. There was poor correlation between initial scores at patient arrival and eventual outcome, while scores 6 hours after presentation correlated better with eventual outcome. Many patients with scores as low as 3 had good neurologic recovery. Patient age, associated injuries, blood pressure, mechanism of injury, presence of spontaneous ventilation, and computed tomographic findings all affected survival. However, considering even these parameters, statistical analysis could not provide sensitive prediction of outcome, which we defined as identifying those patients who eventually had good recovery. We conclude that initial therapy should be aggressive for patients with severe head injury, regardless of initial neurologic status, because accurate prediction of outcome within 6 hours of presentation is impossible. PMID- 1929825 TI - The mangled extremity. When to amputate? AB - To determine indications for immediate or delayed amputation of the mangled lower extremity, we reviewed the cases of 80 patients. Vascular, neurologic, bone, and soft-tissue status were reviewed, as were postoperative complications, requirements for mechanical ventilation, fluid balance, delayed amputation, and survival. Although neurologic, bone, and soft-tissue status did influence decisions regarding immediate amputation, they had little to do with delayed loss of limb or life. The circulation, as determined by the presence or absence of a palpable or Doppler-detected pulse, however, was critical. Of six patients in whom salvage was attempted and in whom fluid balances of greater than 3 L were detected in the first 24 hours post-operatively, five eventually required amputation. Salvage should usually be attempted if a distal pulse is present. If no distal pulse is present, the decision for immediate amputation should be based on functional prognosis. In cases in which salvage is attempted, amputation should be performed at 24 hours if the patient's condition, including a markedly positive fluid balance, indicates systemic compromise. In the absence of a distal pulse on presentation, the eventual amputation rate is high. PMID- 1929826 TI - Limb salvage vs amputation for critical ischemia. The role of vascular surgery. AB - Since 1980, 498 patients with 627 critically ischemic legs (rest pain, gangrene, ischemic ulcer, and ankle-brachial pressure index less than 0.40) were treated with revascularization regardless of operative risk or anticipated operative difficulty. Primary amputation was performed only when no graftable distal vessels were present (14 primary amputations [2.8%]) or in neurologically impaired, hopelessly nonambulatory patients. The mortality for revascularization was 2.3%, and the median hospital stay was 11 days. During follow-up, 41 limbs (7%) required amputation, 31 after failure of revascularization and 10 despite patent revascularizations. Renal failure had an adverse influence on limb salvage (67%) because of a significantly increased requirement for amputation despite patent revascularizations. We conclude aggressive limb revascularization in patients with critical lower-extremity ischemia results in low operative morbidity and mortality and excellent long-term limb salvage. Patients with critical leg ischemia and renal failure are at higher risk for limb loss than patients without renal failure. PMID- 1929827 TI - Hepatic vein and retrohepatic vena caval injuries in children. Sternotomy first? AB - Major hepatic vein and retrohepatic vena caval injuries are often fatal because of massive uncontrollable hemorrhage. Children with these injuries can be identified by their unique and dramatic clinical presentation and the selective use of computed tomographic imaging. Volume resuscitation promotes abdominal wall tamponade and hemodynamic stability until the abdomen is opened, at which point there may be sudden exsanguination before vascular control can be obtained. An alternative approach is to open the sternum before opening the abdomen. Management in this sequence provides rapid vascular control and improves the efficiency of hepatic exclusion. To date, five children with major hepatic vascular injuries have been treated with the sternotomy-first approach and four have survived; an atriocaval shunt was used on two occasions. Although sternotomy before laparotomy improves the efficiency of hepatic exclusion and may offer improved survival, accurate preoperative case selection limits its routine use. PMID- 1929828 TI - Wound healing after anorectal surgery in human immunodeficiency virus-infected patients. AB - Medical records of 52 human immunodeficiency virus (HIV)-infected patients who underwent a total of 80 anorectal operations from January 1985 to January 1990 were retrospectively reviewed to determined whether anorectal surgical wounds healed in HIV-infected patients and the mean survival time of these patients after surgery. Twenty-four operations were performed in asymptomatic HIV-infected patients, 19 in HIV-infected patients with persistent lymphadenopathy, and 37 in patients with acquired immunodeficiency syndrome. Wounds healed in 49 patients (94%). The mortality rate 30 days after surgery was 2%. There were no major complications. The mean survival time of HIV-infected patients after surgery was 15 months. We conclude that anorectal surgical wounds heal in most HIV-infected patients and that the survival time after surgery of HIV-infected patients with anorectal disease justifies appropriate surgical treatment. PMID- 1929829 TI - Surgical management of pneumothorax in patients with acquired immunodeficiency syndrome. AB - Pneumocystis carinii pneumonia in a patient with acquired immunodeficiency syndrome may cause severe alveolar damage, resulting in pneumothoraces that are often bilateral, recurrent, and refractory to accepted methods of treatment. The clinical features, management, and follow-up results were assessed in 22 consecutive patients who presented with a pneumothorax and acquired immunodeficiency syndrome. Seventeen patients died within the time frame of this study. Their average survival time was 147 days. Five surviving patients have lived an average of 366 days. We proposed an algorithm to assist in the management of pneumothoraces in these patients. We concluded that pneumothorax in patients with acquired immunodeficiency syndrome is prognostic of short-term survival. The results in the treatment of pneumothorax in the patient with acquired immunodeficiency syndrome are related to the pathologic lesions of the lung that are associated with Pneumocystis pneumonia and not to the surgical treatment that is employed. PMID- 1929830 TI - The impact of liver reductions in pediatric liver transplantation. AB - Reduced-size liver transplantation (RSLT) in children was introduced to alleviate a shortage of small-organ donors. The impact of RSLT on the waiting time for an organ and on morbidity and mortality was investigated. Between March 25, 1988, and August 11, 1990, 61 hepatic transplantations were performed in 55 children at the Pacific Transplant Institute in San Francisco, Calif. Full-size liver transplantation was performed in 41 cases and RSLT in 20 cases. The overall 30 month actuarial patient and graft survival rates were 89% and 73%, respectively. A comparison between full-size liver transplantation and RSLT showed no difference in patient and graft survival, reoperations, infections, or rejection. Benefits of RSLT were an increase in the donor pool size, a decrease in waiting time for a suitable donor, and a decrease in the rate of arterial thrombosis. The main morbidity of RSLT was an increase in perioperative blood requirement. We conclude that RSLT offers small children with end-stage liver disease a chance for long-term survival. PMID- 1929831 TI - Decortication for childhood empyema. The primary provider's peccadillo. AB - Of the 31 children treated for empyema thoracis secondary to pneumonitis at the Loma Linda University Medical Center, Loma Linda, Calif, from 1980 to 1990, 23 responded to prompt directed antibiotic therapy coupled with drainage, usually tube thoracostomy. All patients were cured clinically; some demonstrated residual pleural reaction with chest roentgenography or computed tomography that resolved over time. Decortication was necessary in eight severely ill children; three required concurrent lung resection for abscess. Distinct from the nonoperated group, there was a pattern of initial antibiotic trials in these patients averaging 6.5 different drugs plus delayed drainage of effusions. Delay in the initiation of antibiotic therapy was six times longer for the operated vs the nonoperated group. Delay to tube thoracostomy was 18 days for the decorticated children compared with 5.4 days for the nondecorticated children. All eight children responded completely and rapidly to their decortications. Roentgenographic changes lagged considerably behind the clinical course of the child, and computed tomographic scans provided better identification of chest tube placement but little information predictive of the need for decortication. Decortication for empyema seldom is necessary when a child is treated promptly with appropriate antibiotics directed by thoracentesis findings, and drainage, usually tube thoracostomy. The criterion for decortication is persistent sepsis, not the roentgenographic appearance of the chest. PMID- 1929832 TI - Effect of donor-disseminated intravascular coagulation in liver transplantation. AB - It is not known whether disseminated intravascular coagulation, present in a large percentage of organ donors, affects patient outcome after liver transplantation. We reviewed our first 55 liver transplantations and identified 10 donors with disseminated intravascular coagulation. We compared the perioperative courses of the 10 recipients of these transplanted livers with those of 10 matched controls whose donors did not have disseminated intravascular coagulation. Disseminated intravascular coagulation recipients did not require more blood products during or after surgery; their hepatic enzyme levels and prothrombin times after surgery were not statistically significantly higher than those of the controls. There was no difference in hospital stay, number of episodes of rejection, retransplantations, or deaths. The presence of disseminated intravascular coagulation in donors did not adversely affect graft function or patient outcome and should not be a sole criterion for rejecting a liver for transplantation. PMID- 1929833 TI - Surgical resection of pulmonary metastases from colorectal adenocarcinoma. Special reference to repeated pulmonary resections. AB - Pulmonary resection of metastatic lesions from colorectal adenocarcinoma was performed in 35 patients. The cumulative 5-year survival was 38%. The primary site of cancer was the colon in about half of the patients. Patients with a solitary metastasis or tumors smaller than 3 cm in diameter survived longer than did patients with multiple metastases or tumors larger than 3 cm but the differences were not significant. Other factors, including age, sex, histologic grade of tumor, location and stage of primary carcinoma, location of pulmonary metastases, disease-free interval, and type of pulmonary resection, had no apparent influence on survival time. The lung was the major site of recurrence following pulmonary resection. Seven patients underwent two or more pulmonary resections for metastasis from a colorectal carcinoma. At the time of last follow up, four patients were alive and free of recurrent disease at 5, 34, 39, and 58 months after the second pulmonary resection. These data suggest that some patients will survive for a long time following pulmonary resection of colorectal metastases, and for highly selected patients, repeated pulmonary resection may further extend survival. PMID- 1929834 TI - Salvage of hemodialysis access in infected arteriovenous fistulas. AB - Infection combined with additional complications of arteriovenous fistulas is a serious threat to access in patients with upper-extremity polytef (polytetrafluoroethylene) grafts. We present three cases of infected access grafts that were treated with systemic antibiotics, excision of the grafts, and primary anastomosis of the arterialized vein to artery for access salvage. The new arteriovenous fistulas were used immediately, preventing interruptions in hemodialysis regimens. This technique of immediate reconstruction allows the surgeon to utilize the arterialized outflow vein and save other sites of access for future use. PMID- 1929835 TI - Recurrent bronchogenic cyst. An argument for complete surgical excision. AB - A case of a recurrent bronchogenic cyst in a 42-year-old woman 25 years after original resection led to a review of the therapeutic modalities for the management of bronchogenic cysts. Recurrence of bronchogenic cysts is a reason for complete surgical excision of symptomatic bronchogenic cysts at initial presentation. If either asymptomatic or symptomatic bronchogenic cysts are drained or partially excised, long-term follow-up is indicated to detect recurrence. PMID- 1929836 TI - Trauma during pregnancy. A review of 79 cases. AB - Few studies provide data on pregnant trauma patients that can be used to direct management decisions. Therefore, this retrospective study of 79 pregnant patients who were injured and admitted to a trauma center during a 9-year period was conducted to obtain such information. Maternal mortality for these pregnant patients was 10%, which was not different from that for nonpregnant females. Overall, rate of fetal loss was 34%. Rates of fetal loss were not different in patients with and without evidence of shock and/or hypoxia or in restrained and unrestrained automobile occupants. Diagnostic peritoneal lavage proved to be 95% accurate and safe. Based on these findings, we concluded the following: pregnancy does not increase maternal mortality from trauma. Blood pressure, pulse rate, and PO2 are unreliable indicators of adequate maternal resuscitation and fetal well being. Assumption of maternal and fetal stability based solely on these usually standard criteria is unwise. Use of seat belts during pregnancy is advisable in the absence of evidence that restraints increase the rate of fetal loss. PMID- 1929837 TI - Trauma in pregnancy. Predicting pregnancy outcome. AB - A multicenter study involving three American College of Surgeons Level 1 trauma centers was undertaken to assess parameters that may predict fetal outcome. The records of 93 injured pregnant patients admitted from April 1, 1985, to March 31, 1990, were reviewed. There were three maternal deaths (3%) (mean Injury Severity Score, 43). Fourteen fetal/neonatal deaths (15%) occurred during the acute care admission period. Of these, eight were fetal deaths (two associated with maternal death), four were cases of elective abortions, and two were neonatal deaths. In general, the maternal physiologic and laboratory parameters assessed failed to accurately predict pregnancy outcome, while Injury Severity Score did differ significantly between patients whose pregnancies were viable (Injury Severity Score = 6.2) and those whose pregnancies were nonviable (Injury Severity Score = 21.6). Unique to this study were the findings that the Glasgow Coma Score also differed significantly in patients with viable (Glasgow Coma Score, 14.5) and nonviable (Glasgow Coma Score, 12.0) pregnancies, while fetal heart rate at admission to the emergency department did not. In this study, the incidence of fetal death was increased following direct uteroplacental fetal injury (100% of cases), maternal shock (67%), pelvic fracture (57%), severe head injury (56%), and hypoxia (33%). The adequacy of noninvasive maternal monitoring in assessing fetal well-being is challenged, and a discussion of diagnostic modalities for assessment for the injured gravida is set forth. PMID- 1929838 TI - Intravascular plastic catheters. How they potentiate tumor necrosis factor release and exacerbate complications associated with sepsis. AB - We tested the hypothesis that long-term intravascular cannulation exacerbates the harmful effects of an infectious challenge. Four groups of rats were initially studied: rats without intravascular catheters or infection (group 1), rats without catheters with a polymicrobial infection (group 2), rats with catheters but no infection (group 3), and rats with catheters and infection (group 4). Infected animals had an increased mortality and generated a significantly increased tumor necrosis factor response compared with noninfected animals. Animals with catheters and infection generated far less cardiac output than animals from the other three groups. No histologic changes differentiated the four groups. Therefore, the presence of a sterile intravascular catheter significantly increases cardiac dysfunction and mortality rates in rats with chronic bacteremia. These results suggest that intravascular plastic catheters potentiate the destructive cascade of events produced by the host in response to bacteremia. PMID- 1929839 TI - Sulindac inhibits the rate of growth and appearance of colon tumors in the rat. AB - Sulindac (cis-5-fluoro-2-methyl-1-[p-(methylsulfinyl) benzylidene] indene-3 acetic acid), an inhibitor of prostaglandin synthesis, has been reported to cause regression of colon polyps in patients with familial polyposis coli and Gardner's syndrome. We examined the effect of sulindac on the growth of primary colon carcinomas in rats. Colon tumors were induced in 18 rats by repeated subcutaneous administration of dimethylhydrazine. The site and diameter of each tumor were measured via laparotomy and colonoscopy. Rats were randomized to receive either sulindac (10 mg/kg) twice daily or vehicle (0.5% methylcellulose). After 4 weeks of treatment, the site and size of tumors in the colon were again recorded. In eight rats receiving sulindac, no new tumors were identified, while in 10 control rats, 13 additional tumors were found after treatment. There was a significantly greater increase in size of the tumors in the control group (56.4 mm for 26 tumors) compared with the rats receiving sulindac (9.3 mm for 14 tumors). We report that sulindac inhibits the rate of development and the rate of growth of colon tumors in the rat. PMID- 1929840 TI - Recurrent inguinal hernia treated by classical hernioplasty. AB - The treatment of recurrent inguinal hernia by classical hernioplasty, ie, via the anterior approach and using endogenous tissue for repair, was evaluated in 163 patients operated on between 1980 and 1987. One hundred fifteen patients had a first recurrence and 48 had a multiple recurrence; 58% were of the direct type; 30% were of the indirect type; 7% were of the combined type; and 5% were not defined. In 1989 a questionnaire was sent to all patients; those indicating symptoms of recurrence underwent further examination. There was a mean follow-up of 52 months and a total follow-up period of 706 years. Thirty-seven patients had a repeated recurrence with a cumulative recurrence rate of 16%, 21%, and 23%, after 1, 2, and 5 years, respectively. Increase of age and time passed since the last repair reduced the recurrence rate. Increased abdominal pressure, type of anesthesia or surgical technique, and wound hematoma had no effect. It is concluded that the technique of classical hernioplasty as such may be unsuitable for repair of recurrent inguinal hernias. PMID- 1929841 TI - Chronic mesenteric vascular syndrome. Results of reconstructive surgery. AB - Since 1961, 14 patients at the University Hospital of Leiden, the Netherlands, have undergone reconstructive surgery for treatment of chronic mesenteric vascular syndrome. Of the 42 mesenteric arteries, 31 were severely obstructed (mean, 2.2 stenotic arteries per patient). A total of 23 mesenteric arteries were repaired. Long-term follow-up data were available for all 13 surviving patients (mean follow-up, 11.8 years). Symptoms were relieved immediately after surgery, and relief was maintained during follow-up. Digital subtraction angiography at long-term follow-up evaluation was performed in eight patients (13 reconstructions) with these results: 11 (85%) of the 13 reconstructions were patent and severe stenoses were found in eight (33%) of the 24 mesenteric arteries (mean, 1.0 stenotic artery per patient). We conclude that reconstructive surgery for patients with chronic mesenteric vascular syndrome promptly relieves symptoms, provides excellent patency, and has long-lasting beneficial results. PMID- 1929842 TI - Role of oxygen-derived free radical scavengers in the treatment of recurrent pain produced by chronic pancreatitis. A new approach. AB - This randomized double-blind trial examined the influence of the radical scavengers allopurinol (50 mg per rectum, four times per day) and dimethyl sulfoxide (500 mg per rectum, four times per day) on pancreatic pain treated with intramuscular pethidine hydrochloride (100 mg followed by 50 mg every 4 hours until complete pain relief) in patients given nothing orally and intravenously hydrated. Addition of allopurinol or dimethyl sulfoxide to the analgesic regimen significantly enhanced its efficacy, enabling at least 57% (13 patients receiving allopurinol and 12 patients receiving dimethyl sulfoxide) of 43 patients to be free of pain within 12 hours after admission compared with only four (17%) of 23 controls achieving the same effect. This advantage extended to all patients within 24 hours after admission, leaving 11 controls (48%) still in pain. Consequently, all patients given allopurinol or dimethyl sulfoxide were discharged 3 days after admission, a result realized in only five (22%) of the assessable controls who were discharged after 5 days of hospitalization. The results suggest that oxygen-derived free radicals are implicated in the mechanism of abdominal pain caused by alcohol-induced chronic pancreatitis and that removing them results in a beneficial therapeutic effect. PMID- 1929843 TI - A prospective, randomized comparison of computed tomography with conventional diagnostic methods in the evaluation of penetrating injuries to the back and flank. AB - We prospectively compared computed tomography with conventional diagnostic methods in the evaluation of penetrating injuries to the back and flank in 85 patients. Immediate laparotomy was performed in 24 patients because of physical findings, and these patients were not randomized. Nine unnecessary operations were performed in this group, and these nine patients had significantly higher hospital costs than patients in either randomized group. In the randomized patients, there were only three true-positive and three false-positive findings. Both computed tomographic evaluation (31 patients) and conventional evaluation (30 patients) were highly accurate and specific for injuries that required operation. Evaluation with computed tomography required a longer time to make a hospital disposition but required fewer diagnostic tests. Computed tomography can be useful in the assessment of penetrating injuries to the back and flank. PMID- 1929844 TI - An evaluation of surgery departments in community-based medical schools. AB - Since 1960, most newer medical schools have been community-based and have used existing community hospitals and a large number of volunteer faculty. As these schools have evolved, many have developed more traditional characteristics. To assess the positive and negative features of these new schools, chairs of departments of surgery from 21 community-based medical schools and 17 traditional schools were surveyed to acquire information on policies and practices related to faculty development, undergraduate and graduate education, hospital relationships, clinical activities, research, and relationships with community physicians. Responses were analyzed and compared. Most community-based schools have succeeded in their mission, partly at the expense of controls usually found in more traditional schools. PMID- 1929845 TI - Cigarette smoking decreases tissue oxygen. AB - Subcutaneous wound-tissue oxygen (PsqO2) tension in eight volunteers fell rapidly and significantly in response to smoking, and remained low for 30 to 50 minutes. Sham "smoking" had no effect. These data suggest that a typical "pack-per-day" smoker experiences tissue hypoxia during a significant portion of each day. The degree of hypoxia found in these subjects has been associated with poor wound healing in animal and human studies. The onset and duration of tissue hypoxia paralleled the well-established plasma pharmacokinetics of nicotine. This suggests that peripheral vasoconstriction, induced by the adrenergic effects of nicotine, may contribute to the observed decrease in PsqO2. PMID- 1929846 TI - Race and liver transplantation. AB - Little is known about the effect of race on the outcome of liver transplantation. We retrospectively reviewed a series of 358 recipients of orthotopic liver transplants to address this issue. Black recipients were underrepresented compared with the general population (6% of transplant recipients vs 12% of the population). Black recipients appeared sicker when presenting for transplantation, as evidenced by a higher priority score and a significantly greater incidence of acute and fulminant presentation. Despite this, black recipients had survival rates following transplantation that were not significantly different from those of white recipients; the 1-, 2-, and 3-year actuarial survival rates of blacks were 89.6%, 68.3%, and 68.3%, respectively, while the actuarial survival rates of whites at the same periods were 86%, 82.4%, and 78.6%, respectively. We conclude that blacks can have an outcome equal to whites following liver transplantation but they are underrepresented compared with the general population. PMID- 1929847 TI - Gastric volvulus in the pediatric population. AB - Acute gastric volvulus in children is uncommon. Since 1899, only 77 cases have been documented in the world literature. In children, mesenteroaxial volvulus is the most common type and associated anatomic defects are the rule. Diagnostic delays result in gastric ischemia, perforation, and death. Nonoperative mortality is 80%. Early recognition, surgical reduction with gastric fixation, and repair of associated defects are the mainstays of therapy for acute gastric volvulus in the pediatric population. PMID- 1929848 TI - Cancer of bile duct with situs inversus. AB - We present a case of adenocarcinoma of the distal common bile duct in a 68-year old woman with total situs inversus. Endoscopic retrograde cholangiopancreatography prior to surgery demonstrated segmental obstruction of the distal common bile duct. Obstructive jaundice was observed and the results of liver function studies were abnormal. All biopsy specimens obtained in the operating room were negative. The case met all the criteria of Child and Frey, but at the end of the procedure the tumor was found to involve the superior mesenteric vein, a factor not appreciated during the operative evaluation of the patient. The situs inversus did not produce any technical problems. The patient did not have any surgical complications, but she died 18 months later of the cancer. PMID- 1929849 TI - Efferent limb obstruction after pancreaticojejunostomy. A late cause of pancreatitis following Whipple resection. AB - A previously unreported late complication after Whipple resection of the head of the pancreas was recognized in two patients. Obstruction by adhesions and kinking of the efferent jejunal conduit between the proximal pancreaticojejunostomy and the distal choledochojejunostomy led to repetitive episodes of acute pancreatitis without jaundice. Operative recognition and correction of the obstruction resulted in prevention of further attacks. PMID- 1929851 TI - Mutagenicity and cytotoxicity of two regioisomeric mercapturic acids and cysteine S-conjugates of trichloroethylene. AB - The mutagenicity, cytotoxicity and metabolism of two regioisomic L-cysteine- and N-acetyl-L-cysteine-S-conjugates of trichloroethylene were studied. The 1,2 dichlorovinyl(1,2-DCV) isomers of both the cysteine conjugate and the mercapturate were much stronger mutagens in the Ames test with Salmonella typhimurium TA2638 when compared to the corresponding 2,2-dichlorovinyl (2,2-DCV) isomers. Similarly, the 1,2-DCV isomers were more cytotoxic towards isolated rat kidney proximal tubular cells, as assessed by inhibition of alpha-methylglucose uptake, than the 2,2-DCV isomers. The 3-4-fold higher rate of beta-lyase dependent activation of S-(1,2-dichlorovinyl)-L-cysteine (1,2-DCV-Cys) when compared to S-(1,2-dichlorovinyl)-L-cysteine (2,2-DCV-Cys) as well as the different nature of the reactive intermediates formed is probably responsible for these structure-dependent effects. The cytotoxicity of N-acetyl-S-(1,2 dichlorovinyl)-L-cysteine (1,2-DCV-NAc) toward isolated kidney cells showed a delayed time course as compared to that of 1,2-DCV-Cys, probably due to the relatively low rate of deacetylation of 1,2-DCV-NAc. The time course of cytotoxicity of N-acetyl-S-(2,2-dichlorovinyl)-L-cysteine (2,2-DCV-NAc), however, parallelled that of 2,2-DCV-Cys. Due to the relatively high rate of N-acetylation and low rate of beta-lyase activation, for 2,2-DCV-Nac the beta-lyase activation step may be rate limiting. Different rates of cellular uptake also may play a role in time course of toxicity of the cysteine conjugates and the mercapturic acids in the renal cells. PMID- 1929852 TI - Urinary excretion of ethylenethiourea and kidney morphology in rats after continuous oral exposure to nabam or ethylenethiourea. AB - Nabam, an ethylenebisdithiocarbamate (EBDC), is an agricultural fungicide. Ethylenethiourea (ETU), widely used in the rubber industry, is a degradation and byproduct of metabolism and of storage and production of EBDCs. Kidney function and morphology, and urinary excretion of ETU, were studied in rats exposed to nabam or ETU in drinking water for 28 days. The concentrations of nabam in drinking water were 0, 50, 100 or 200 mg/l, and of ETU 0, 100, 200 or 300 mg/l. Both compounds decreased body weight gain but did not significantly affect urinary sodium, potassium, glucose, or protein excretion, or urinary osmolality. Urinary vasopressin was also unaltered after exposure to nabam or ETU. High doses of ETU resulted in ultrastructural alterations in epithelial cells of renal proximal tubuli. ETU was excreted in urine after exposure to both nabam and ETU. There seemed to be a threshold dose of ETU below which no ultrastructural alterations in kidney occurred. PMID- 1929850 TI - Biomechanisms of cocaine-induced hepatocyte injury mediated by the formation of reactive metabolites. AB - Cocaine is an intrinsic hepatotoxin in laboratory animals, and there is growing evidence that high doses of cocaine can precipitate hepatic necrosis in humans. The rodent model of cocaine hepatotoxicity is commensurate with the concept that a multistep mainly cytochrome P-450 dependent N-oxidative pathway is responsible for the expression of hepatocellular injury. Among the possible biomechanisms by which cocaine exerts its cytotoxic effects, direct oxidative damage by reactive oxygen species generated by redox cycling during the metabolic cascade seems most important. The role of the ensuing lipid peroxidation and protein thiol oxidation is less clear. Similarly, the functional role of irreversible (covalent) binding of a not yet defined electrophilic cocaine intermediate to hepatocellular proteins remains enigmatic so long as the critical molecular targets have not been identified. Finally, glutathione plays a pivotal protective role against cocaine-induced hepatic injury. Interactions with ethanol or inducers of the expression of the cytochrome P-450IIB subfamily can potentiate cocaine hepatotoxicity. Thus, the net amount of the ultimate reactive species seems to determine the severity of the hepatic lesions and to be responsible for the marked interspecies, interstrain, and sex differences. Recent advances in culture techniques of hepatocytes and precision-cut liver slices from various species including man have made it possible to correlate cocaine biotransformation with cytotoxicity and to selectively study the putative cellular mechanisms. Clearly, more studies are necessary to further illuminate our understanding of the role of the biochemical and molecular events precipitating hepatic necrosis during cocaine-mediated hepatotoxicity. PMID- 1929853 TI - Induction of macrophage plasminogen activator by asbestos is independent of PKC activation. AB - This study was undertaken to assess whether plasminogen activator (PA) induction in macrophages exposed to chrysotile fibers is mediated by protein kinase C (PKC) activation. In PKC depleted J774 cells, PA induction could be elicited by chrysotile whereas, as expected, the response to phorbol myristate acetate (PMA) was abolished. The effect of PMA and chrysotile on the distribution of PKC activity in the J774 cell line was also compared by measuring the enzyme catalytic activity and phorbol dibutyrate (PDBu) binding sites. No redistribution of PKC was observed after stimulation with PA inducing doses of chrysotile, whereas a clear translocation was observed with PMA. It is concluded that the mechanism of PA induction by chrysotile in this macrophage-like cell line is independent of PKC activation. PMID- 1929854 TI - Embryotoxicity induced by alkylating agents: 6. DNA adduct formation induced by methylnitrosourea in mouse embryos. AB - Formation of DNA adducts in 11-day-old mouse embryos was studied by measuring the initial alkylation rates of the methylated purine bases 7-methylguanine, O6 methylguanine, and 3-methyladenine. In the first part of the studies the adduct rates were measured in the teratogenic dose range (ED10-ED90, 2.7-5.6 mg/kg). These results were compared with similar data obtained from studies with ethylmethanesulfonate and acetoxymethyl-methylnitrosamine. For the three investigated substances a correlation was found between the initial adduct rate of O6-alkylguanine in the DNA of the embryos and the teratogenic potency. In the second part of the study the rate of adduct formation was measured in the sub teratogenic dose range. These data will be used for molecular dosimetry in a risk assessment of low doses. PMID- 1929855 TI - Preventive effects of methylcobalamin on the testicular damage induced by ethylene oxide. AB - In this study, the effects of methylcobalamin on testicular damage induced by ethylene oxide (EtO) were studied. When Wistar male rats inhaled EtO at 500 ppm, 6 h a day, 3 days a week, for 6 weeks, testicular damage was observed histopathologically and by some other parameters. Subcutaneous injection of methylcobalamin at 500 micrograms/kg, 5 times/week was found to ameliorate the damage. However, the degree of the methylcobalamin effect differed among the parameters examined in this study. Decrease in testicular weight due to EtO exposure was completely prevented by methylcobalamin, and decrease in testicular mature spermatid count and LDH-X activity was fairly well prevented. The degree of prevention of alteration in the epididymis, such as epididymal weight, epididymal sperm count and sperm abnormality rate, was significant but not complete. EtO caused apparent alterations in glutathione metabolism in the testes, but methylcobalamin did not affect such alterations induced by EtO. From these results, it has been determined that methylcobalamin has definite preventive effects on testicular toxicity of EtO. PMID- 1929856 TI - Effect of aciclovir on the development of the chick embryo in ovo. AB - The effect of aciclovir (ACV) on embryonic development was investigated using the chick embryo in ovo and treatment during organogenesis. ACV 30-1000 micrograms was applied as single doses prior to or after 24 h of incubation into the yolk sac, and ACV 3-100 micrograms after 2, 3 or 4 days of incubation (DI) directly to the embryo. Data were evaluated after a total of 8 days of incubation. (1) A dose related increase in the rate of abnormal development was found in the surviving embryos. Depending on the route of drug administration a dose of 300, respectively, 5 micrograms ACV/egg had to be applied to induce 50% abnormal development. (2) Gross structural abnormalities of the surviving embryos mainly concerned the beak and the extremities. With the experimental set-up used a different pattern of abnormalities in the survivors after treatment at various stages could not be observed. The results are compared with data obtained with ACV in rodents in our laboratory. It is suggested that chick embryos are also capable of converting ACV into its triphosphate to interfere with DNA metabolism, probably through a chain break mechanism. PMID- 1929857 TI - Cytoskeletal changes induced by 2,5-hexanedione on developing human neurons in vitro. AB - Dissociated dorsal root ganglion cells from human fetuses were exposed to 2,5 hexanedione (2,5-HD) for 2 weeks. Morphological changes induced by 2,5-HD consisted in focal neurofilament (NF)-containing enlargements preferentially located in distal, preterminal regions of unmyelinated fibers. Tangles of NF were also observed in the perikarya of nerve cells. Morphometric analysis disclosed that the cross-sectional areas of the 2,5-HD treated axons were 30% smaller than those of control axons. This alteration was associated with reduction of number of NF per unit area. These findings demonstrate that 2,5-HD treatment induces a generalized disorganization of neuronal and axonal NF responsible for focal enlargements as well as atrophic changes of unmyelinated fibers. PMID- 1929858 TI - Evidence for the disruption of the bone marrow microenvironment by combined exposures to inhaled benzene and ingested ethanol. AB - Studies have been performed to investigate the effects of combined in vivo exposures to inhaled benzene and ingested ethanol on the earliest known murine erythropoietic precursor cells, the Burst Forming Unit--Erythroid (BFU-E) and the Colony Forming Unit--Erythroid (CFU-E). Previously we had determined that murine erythropoietic cell populations were particularly susceptible to combined benzene + ethanol treatments. The most striking example of erythropoietic disruption was the transient appearance of large numbers of nucleated red cells (normoblasts) in the circulating blood. In the present studies, male C57Bl/6 mice were exposed to 300 ppm benzene via inhalation for 6 h/d x 5 d/wk x 9 wks. Groups of mice were also exposed to 5% ethanol in the drinking water 4 d/wk x 9 wks. Appropriate controls were also maintained. The hematological assays were performed after 1, 4, and 9 weeks of exposure. After 4 weeks of exposure large numbers of normoblasts appeared in the circulating blood of mice exposed to benzene + ethanol. However, there were no corresponding increases in the numbers of the earliest erythroid progenitor cells in the bone marrow. There were, however, marked increases in the numbers of these cells in the spleen. Previous work in this laboratory had confirmed that the marrow was the source of circulating normoblasts among animals exposed to benzene + ethanol. We conclude, therefore, that circulating normoblasts appear in the peripheral blood because of changes in the bone marrow microenvironment rather than as a consequence of increased erythropoietic proliferation in the marrow. PMID- 1929859 TI - Penetration, distribution and kinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in human skin in vitro. AB - The in vitro penetration of 3H-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into human cadaver skin was studied at concentrations of 65 and 6.5 ng TCDD per cm2 of skin surface. Vehicles used were acetone to simulate exposure to TCDD as a dry material, and mineral oil to simulate exposure to TCDD in an oily medium. Penetration was performed for 30, 100, 300, and 1000 min in improved Franz cells. Skin was used either intact, or with stripped horny layer. Skin was sectioned along its natural layers and radioactivity determined in epidermis and dermis. TCDD did not readily penetrate into human skin in vitro. The vehicle of exposure to TCDD played an important role in dermal penetration. The rapidly evaporating acetone allowed TCDD to penetrate deeply into the loose surface lamellae of the horny layer, but then appeared to be poorly available for further penetration. Mineral oil as the vehicle, on the other hand, represented a lipophilic compartment which competed with lipophilic constituents of the stratum corneum for TCDD and hence slowed its penetration even more. The stratum corneum acted as a protective barrier, as its removal increased the amount of TCDD absorbed into layers of the skin. Hourly rates of absorption of TCDD per unit area of skin were calculated in two ways: a worst case scenario where TCDD absorbed into any layer of skin including the stratum corneum was used for regression analysis; and a physiological approach where only that amount of TCDD was considered absorbed which had penetrated beyond the epidermis into the region of dermal vascularization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929860 TI - Increased copper concentrations in rat tissues after acute intoxication with 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - Recently, acutely toxic doses of the environmental pollutant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) have been reported to affect the hepatic distribution of essential metals in the rat. However, the reduced food intake by TCDD was not taken into account. Therefore, metal concentrations were determined in different rat tissues at the end of a toxicity study with TCDD in which a pair fed control group was introduced. Male Sprague-Dawley rats received a single i.p. injection of corn oil/acetone with or without TCDD at 125 micrograms/kg. Controls and TCDD-treated rats were fed ad libitum; additionally, pair-fed controls received the amount of food consumed by their TCDD-treated partners 1 day before. Twenty-one days after dosing rats were killed and samples of liver, kidney and jejunum were taken for the analysis of Ca, Cu, Fe, Mg, Mn, and Zn. After acid digestion of the tissues metals were determined by atomic emission spectrometry (AES). The most outstanding effect of TCDD treatment was an increase of the copper levels in the kidney (4-fold, versus pair-fed controls) and in the liver (greater than 2-fold, versus pair-fed controls). Other metals were mainly affected by the reduced food intake only. Since Cu represents a trace metal the homeostasis of which depends on its biliary excretion and since TCDD is known to impair biliary flow and excretion, an impaired biliary excretion of Cu by TCDD is suggested as the causal mechanism. PMID- 1929861 TI - Gas chromatographic determination of butoxyacetic acid in human blood after exposure to 2-butoxyethanol. AB - Venous blood samples from five male volunteers exposed to 20 ppm 2-butoxyethanol (BE) for 2 h were collected at 0, 2, 4, and 6 h from the start of exposure and analyzed by gas chromatography after simultaneous ion-pair extraction and derivatization with pentafluorobenzyl bromide. Butoxyacetic acid (BAA), a major metabolite of BE, was found in all samples except those collected prior to exposure. This is the first time to our knowledge that the analysis of BAA in human blood has been reported. Concentrations of BAA in blood ranged from 22 to 60 microM. These concentrations were about two orders of magnitude lower than those causing swelling and hemolysis of human erythrocytes in vitro. The BAA blood level peaked after 2-4 h. The decrease between 4 and 6 h indicates an average half-time of BAA in blood of about 4 h, which is in accordance with previously observed half-times in urine. The low renal clearance of BAA (22-39 ml/min) indicates extensive binding to blood proteins and poor tubular secretion of the substance. Binding of BAA to blood components is also indicated by the low apparent volume of distribution of approximately 15l. PMID- 1929862 TI - Distribution of lipophilic xenobiotics among plasma lipoproteins. PMID- 1929863 TI - Mechanisms of cell death. AB - Two distinct morphological patterns of cell death have been recognized, termed necrosis and apoptosis. Apoptosis, or programmed cell death, occurs in both physiological and pathological conditions. It arises due to an elevation of cytosolic free calcium concentration resulting in activation of a nuclear endonuclease. Activated endonuclease produces oligonucleosome-length DNA fragments. This DNA cleavage can directly precipitate cell death. Both glucocorticoids and TCDD may induce apoptosis by production of a heat labile factor that mediates calcium influx whereas tributyltin causes the opening of calcium channels. Evidence that perturbation in calcium homeostasis is an important event in cell necrosis is becoming increasingly persuasive, but the events that propagate the lesion are still unclear. Despite evidence for cytoskeletal disruption, activation of degradative enzymes such as proteases and phospholipase A2 and stimulation of other enzymes such as poly (ADP-ribose) polymerase, the exact role that these play in cell killing is not resolved. Indeed, recently the radical dichotomy between apoptosis and necrotic cell death has come into question. It is clear that further work is required to determine the role played by some elements of the apoptotic process in chemically induced cell death. PMID- 1929864 TI - A brief review of modern toxicologic pathology in regulatory and explanatory toxicity studies of chemicals. AB - Macroscopic and histologic evaluation of animal studies for general toxicity and carcinogenicity are cornerstones of the risk assessment of new chemical entities. Standard toxicopathologic evaluation is mainly based on the study of paraffin sections stained with hematoxylin and eosin. There are, however, a number of new approaches and techniques which have improved the objectivity of evaluation and the accuracy of cell identification, and provided deeper insight into the molecular biological mechanisms of toxicity and carcinogenicity. Such approaches include the standardization of the nomenclature, the creation of data banks for morphological alterations, the use of computers to register pathological findings in toxicity studies and to statistically evaluate incidences, and the use of morphometry. Other modern techniques are immunohistochemistry, in situ hybridization, and the assessment of cell kinetics. PMID- 1929866 TI - Tactile-kinesthetic system of rats as an animal model for minimal brain dysfunction. AB - A previous study showed that rats exposed to methylmercury during development exhibit effects similar to those described for children with minimal brain dysfunction (MBD), namely, hyperactivity, altered locomotion structure, and unaltered learning ability, but reduced and more variable attention spans induced by increasing difficulties within an operant learning paradigm. Psychopathological studies suggest that behavioral disturbances of the MBD type may originate directly or indirectly from deficiencies in the tactile-kinesthetic system. This sensory modality is the main mechanism by which an individual organism assimilates reality. Deficiencies in the tactile-kinesthetic system impair the action of the equilibration processes (in Piaget's sense) which ensure that the stages of psychological development occur in an orderly sequence. The lack of this control over development may result in the behavioral characteristics of MBD. Problems with the tactile-kinesthetic system may also be the reason for the deficiencies of fine motor control in MBD children. In an attempt to extrapolate this interpretation of human psychopathological mechanisms to experimental animals, an operant paradigm was developed for the assessment of the tactile-kinesthetic system of rats, the schedule of "differential reinforcement of force range" (DRF). Rats were trained to press in discrete trials a force sensitive lever during at least 1 s between two force thresholds of 60 and 80 g without any feedback other than the rats' own tactile-kinesthetic perception. Offspring of rat dams exposed to 1.5 and 5 mg/l methylmercury chloride in their drinking water from 2 weeks before pairing until weaning, exhibited a clearcut performance deficit (approximately 25% correct responses compared to approximately 50% of the controls).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929865 TI - Single cell analysis in toxicity testing: the mitogenic activity of thioacetamide in cultured rat hepatocytes analyzed by DNA/protein flow cytometry. AB - Rat hepatocytes were cultured at 4% O2 and 13% O2 and exposed to the nongenotoxic rodent carcinogen thioacetamide (TA) from 24 to 72 h after isolation at exposure levels between 0.01 and 0.33 mM. Hepatocytes and isolated nuclei were analyzed by DNA-protein flow cytometry. An aggregate correction procedure was applied and the proportion of S-phase, diploid, tetraploid or octoploid hepatocytes as well as binucleated cells, were measured or calculated. The proportion of S-phase cells within the diploid hepatocytes increased with increasing concentration of TA up to 3.9-fold, whereas the corresponding increase in S-phase mononucleated tetraploid cells was only 1.8-fold. S-phase binucleate tetraploid cells showed no increase. In the tetraploid hepatocytes, the mitogenic stimuli was detectable only in cultures maintained at 4% O2. The relative contribution of binuclear cells was increased 1.5-fold in the octoploid cells. It is concluded that the mitogenic activity of TA initiates DNA synthesis in diploid hepatocytes in the G1 and in the following G2 cell-cycle phase, omitting karyogenesis. The cellular protein content is not affected which indicates that the mitogenic activity of the chemical is not necessarily associated with an increase in cellular protein content. The results obtained correspond well with data of in vivo studies. The method applied therefore allows the mitogenic activity of nongenotoxic carcinogens to be detected in vitro within 48 h and their mode of action to be elucidated. PMID- 1929867 TI - Recirculating, retrograde heart perfusion according to Langendorff as a tool in the evaluation of drug-induced cardiomyopathy: effects of a high lipid diet. AB - A recirculating, retrograde heart perfusion according to Langendorff is described as a method for the evaluation of cardiomyopathy as an untoward side effect of a high lipid diet (addition of 10% and 25% corn oil to rat maintenance feed) in female rats. The use of glucose (5 mM) or palmitate (0.5 mM/0.1 mM BSA) as substrates during a 2-h perfusion period, and their effects on heart metabolism of control-, LL- and HL-diet fed animals were evaluated. Substrate uptake, LDH release and adenine nucleotides, creatine phosphate, creatine, lactate, pyruvate, glucose-6-phosphate, glycogen, triglyceride and phospholipid content were determined in heart tissue. PMID- 1929868 TI - Neurotoxic effects of chloroquine in vitro. AB - In order to investigate chloroquine retinopathy, the effect of chloroquine on the viability and differentiation of primary cell cultures of embryonic chick neuronal retina, retinal pigment epithelium (RPE), brain and meninges were investigated. The sensitivity of the cells, measured as reduction of viability, showed the following order: RPE greater than brain greater than meninges greater than neuronal retina. The human serum chloroquine concentration range which leads to ocular damage in vivo was identical to the concentration range in the culture medium which affected RPE viability. In addition, the differentiation of nerve cells in brain cell cultures was affected at much lower chloroquine concentrations than astroglia cells or nerve cells in neuronal retina cell cultures. Some possible mechanisms for chloroquine retinopathy were assessed. PMID- 1929869 TI - Toxicity and EROD-inducing potency of 24 polycyclic aromatic hydrocarbons (PAHs) in chick embryos. AB - The toxicities (embryolethality) of 24 polycyclic aromatic hydrocarbons (PAHs) were determined in chick embryos using a 72-h test. The substances, dissolved in peanut oil, were injected into the air sacs of eggs preincubated for 7 days. LD50 values were determined for the four most toxic of the 24 compounds. Benzo[k]fluoranthene proved to be the most potent, with an LD50 of 14 micrograms (56 nmol)/kg egg. Dibenz[a,h]anthracene, benz[a]anthracene and benzo[b]naphthol[2,3-d]thiophene were a few times less toxic [LD50 = 39 micrograms (140 nmol)/kg, 79 micrograms (349 nmol)/kg and 82 micrograms (350 nmol)/kg, respectively]. The LD50 of benzo[k]fluoranthene was only about 5 times higher than that previously found for the most potent coplanar polychlorinated biphenyl (PCB), 3,3',4,4',5-pentachlorobiphenyl [LD50 = 3.1 micrograms (9.4 nmol)/kg], in the same kind of test. The toxicities of 18 of the PAHs in this study have also been evaluated previously using a 2-week test in chick embryos. Dibenz[a,h]anthracene, which had not been studied earlier in the 2-week test, proved to be almost as toxic as previously found for benzo[k]fluoranthene in that test. Several of the PAHs studied induced EROD activity in chick embryos, and, in general, the most toxic PAHs were also the most potent inducers of EROD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929870 TI - Effect of alpha-tocopherol and di-butyl-hydroxytoluene (BHT) on UV-A-induced photobinding of 8-methoxypsoralen to Wistar rat epidermal biomacromolecules in vivo. AB - The possible formation of singlet oxygen via photoexcited psoralens has been associated with the occurrence of, amongst others, erythema. Therefore it has been suggested to combine PUVA with the topical or systemic administration of antioxidants. However, the effect of these antioxidants on the photobinding of psoralens to DNA, which is held responsible for the anti-proliferative effect, should be taken into account. In the present study the effect of two phenolic antioxidants, alpha-tocopherol (AT) and butylated hydroxytoluene (BHT), on the in vivo photobinding of 8-methoxypsoralen (8-MOP) to not only epidermal DNA, but also proteins and lipids was determined. After topical application of an ethanolic antioxidant solution onto the shaven skin of Wistar rats, labeled 8-MOP was applied using the same solvent. After this the rats were exposed to UV-A. By separating epidermal lipids, DNA/RNA and proteins by a selective extraction method, irreversible binding of 8-MOP to each of these biomacromolecules was determined. Both AT and BHT caused a decrease in the photobinding of 8-MOP to epidermal DNA and proteins. To investigate the underlying mechanism of this protection, the effect of AT was compared with that of AT-acetate. It also proved helpful to study the effects of the antioxidants on the photobinding of another photosensitizer, namely chlorpromazine. From these experiments it was concluded that AT and BHT affect 8-MOP photobinding by quenching reactive 8-MOP intermediates, involving the phenolic hydroxyl group of the antioxidants. BHT offered protection against lipid binding of 8-MOP but AT, especially at high concentrations, enhanced the UV-A-induced binding of 8-MOP to lipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929871 TI - Changes in sensitivity of in vitro rat brain protein synthesis to the acute action of ethanol and isopropanol as a consequence of the long-term ingestion of isopropanol. AB - Long-term treatment of rats with isopropanol in the drinking water results in a change or process of adaptation occurring in in vitro brain protein synthesis which increases the resistance of the ribosomal machinery to the acute effect of either ethanol or isopropanol. Such an increase was observed both in the system coded by endogenous messenger and in the system coded by polyuridylic acid. In both translation systems, the adaptation seems to affect the ribosomal step of polypeptide chain elongation. The increase in resistance to the alkanols apparently did not affect the inhibitory action of puromycin, fusidic acid and cycloheximide on the ribosome. PMID- 1929872 TI - Endogenous formation of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3- carboxylic acid in man as the possible causative substance of eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan. AB - 1-Methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) is now thought to be a possible causative substance of eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan. In the present study a factor affecting endogenous formation of MTCA in 32 healthy men is studied. Urinary excretions of MTCA and 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (TCCA) were measured by high-performance liquid chromatography (HPLC) with fluorometric detection after administration of a high or low protein diet as well as peroral tryptophan (0.5 g) or ethanol (0.4 g/kg). Blood ethanol and acetaldehyde levels were determined by gas chromatography after ethanol consumption. Both, the high protein diet and tryptophan resulted in a significant rise of urinary TCCA. In contrast, ethanol intake caused increased excretion of MTCA, though a relationship between blood acetaldehyde level and urinary excretion of MTCA was not shown. We showed for the first time that an elevation of urinary excretion of MTCA following ethanol consumption in man without ingestion of L-tryptophan tablets implicated eosinophilia-myalgia syndrome. PMID- 1929873 TI - Pathobiochemical response of tracheobronchial lymph nodes following intratracheal instillation of polyvinylchloride dust in rats. AB - PVC dust, following a single intratracheal instillation (25 mg/rat), was substantially cleared through the lymphatic circulation and progressively accumulated in the tracheobronchial lymph nodes (TBLN) in a time-dependent manner for up to 1 year. The tissue response in TBLN during 60-270 days post instillation of PVC dust was characterized by progressive increase in total organ fresh weight, dry weight, DNA, RNA and protein contents, concurrent with the proliferation of macrophages and hyperplasia of reticular cells. Active phagocytosis and enhanced hydrolytic activity in TBLN was evident around 270 days post-instillation by the appearance of PVC-laden macrophages near and within the dust foci, and increased activity of acid phosphatase, DNAse, RNAse and beta glucuronidase. PVC dust caused degeneration of macrophages, and consequent release of hydrolytic enzymes resulted in limited cytotoxicity without inducing reticulination and fibrosis in the TBLN. The histology and clinical biochemistry of liver, kidney, spleen and serum were not altered and there were no detectable PVC particles in these tissues at up to 365 days. It is therefore concluded that lymphatic clearance of intratracheally instilled PVC dust results in its accumulation and mild foreign body reaction in TBLN which is non-fibrogenic at up to 365 days post-instillation. PMID- 1929875 TI - Serial propagation of porcine enteric calicivirus in a continuous cell line. Effect of medium supplementation with intestinal contents or enzymes. AB - A porcine enteric calicivirus (PEC) was adapted to serial propagation in a continuous porcine kidney cell line (LLC-PK) by inclusion of an intestinal contents preparation (ICP), derived from uninfected gnotobiotic pigs, in the maintenance medium. Infected cells were detected by immunofluorescent staining of cell monolayers. Attempts to propagate PEC in the presence of various intestinal enzymes of porcine origin, bacterial protease, bovine ICP, avian ICP or without medium supplementation were unsuccessful. PMID- 1929874 TI - The oxime HGG-12 as a muscarinic acetylcholine receptor antagonist without intrinsic activity in cardiac membranes. AB - Direct interactions of the bispyridinium oxime HGG-12 with muscarinic acetylcholine receptors were investigated in porcine cardiac atrial membranes. Competition binding experiments using the radiolabeled muscarinic receptor antagonist (3H)QNB revealed specific binding of HGG-12 to muscarinic acetylcholine receptors of porcine atrial membranes with a dissociation constant of 3.8 x 10(-7) mol/l. Muscarinic acetylcholine receptor-stimulated binding of the radiolabeled GTP analog (35S)GTP[S] to guanine nucleotide binding proteins (G proteins) was used to study antagonistic and possible agonistic effects of HGG-12 at muscarinic acetylcholine receptors. HGG-12 completely inhibited carbachol- and oxotremorine-stimulated (35S)GTP[S] binding to pertussis toxin sensitive and insensitive G-proteins in a competitive manner. Inhibition constants (K1) of HGG 12 for blockade of carbachol- and oxotremorine-stimulated GTP[S]-binding (9.7 x 10(-7) mol/l and 1.7 x 10(-6) mol/l, respectively) were higher by about a factor of 100 than those of the muscarinic acetylcholine receptor antagonist atropine. In the absence of muscarinic acetylcholine receptor agonists. HGG-12 by itself had no stimulatory effect on (35S)GTP[S] binding in porcine atrial membranes. The results of this study show that the oxime HGG-12 is a competitive antagonist without intrinsic activity at porcine atrial muscarinic acetylcholine receptors. The stimulatory action of HGG-12 on muscarinic acetylcholine receptors which has been described by several authors is, therefore, suggested to be due to partial inhibition of acetylcholinesterase by the oxime rather than to direct agonism at muscarinic acetylcholine receptors. PMID- 1929876 TI - A list of proposed standard acronyms for plant viruses and viroids. PMID- 1929877 TI - Synthesis and proteolytic processing of arabis mosaic nepovirus, cherry leaf roll nepovirus, and strawberry latent ringspot nepovirus proteins in reticulocyte lysate. AB - The genomic RNA components of three nepoviruses, arabis mosaic (ArMV), cherry leaf roll (CLRV), and strawberry latent ringspot (SLRV), were translated in rabbit reticulocyte lysate. Each component (except the RNA-2 of CLRV) directed the synthesis of proteins that corresponded in size to their theoretical coding capacity. The RNA-1 components of all three viruses were translated to yield polyproteins of Mr 250k, which were autocatalytically processed to yield up to five cleavage products. The primary products of translation of the RNA-2 components of ArMV (Mr 115k and 105k), CLRV (Mr 165k) and SLRV (Mr 99k and 96k) were polyproteins that were stable on incubation, but which underwent proteolytic processing in the presence of the corresponding RNA-1 and its translation products. These polyproteins were immunoprecipitated using antisera to appropriate virions indicating that the RNA-2 sequences encode the coat protein cistrons. PMID- 1929878 TI - Temporal control for translation of influenza virus mRNAs. AB - cDNAs for genome RNAs of influenza virus A/PR/8/34 were cloned and portions containing the ATG initiation codon for translation were inserted into the 5' leader sequence of the chloramphenicol acetyltransferase (CAT) gene in a pSV2cat vector. In cells that were transfected with a plasmid containing a cDNA segment for the early gene and then super-infected with influenza virus, the maximal CAT activity was obtained at the early stage of infection. In contrast, a plasmid containing a cDNA segment for the late gene directed the highest activity at the late stage of infection. These observations together with the previous observations [K. Yamanaka et al. (1988) Virus Genes 2: 19-30] indicate that the translational efficiency of influenza viral mRNA is subjected to temporal control following viral infection. PMID- 1929880 TI - Viral erythrocytic infection in sea bass: virus purification and confirmative diagnosis. AB - The viral erythrocytic infection (VEI) of sea bass (Dicentrarchus labrax) is evidenced by the presence of inclusion bodies in the erythrocytes and erythroblasts. Virus-like particles (VEIV) about 135-150 nm in diameter were observed in erythroblasts of affected fish. No culturable virus could be recovered from the organs and blood of VEI-affected fish, after inoculation of different fish cell lines. Histochemical staining revealed the presence of RNA but not of DNA in the inclusion bodies. Specific, rabbit hyperimmune sera were prepared after extraction and purification by gel chromatography of viral material from pelleted blood cells of infected fish, and evaluated by immunocytochemical assays. Electron microscopic observations revealed the presence of enveloped particles of about 125-150 nm in the antigenic preparation. The antisera specifically reacted to inclusion bodies, cellular membranes and nuclei of VEI-affected erythrocytes in immunofluorescent and peroxidase antiperoxidase assays. Immunoelectron microscopy in ultrathin sections of head kidney samples from VEI-affected fish showed recognition of inclusion bodies and virus particles. Confirmative diagnostic procedures could be established through the use of specific anti-VEIV sera, which enabled differentiation between similar syndromes described in other fish species. PMID- 1929879 TI - Analysis of non-infectious HIV particles produced in presence of HIV proteinase inhibitor. AB - Newly developed substrate analogue peptidomimetics are able to inhibit the human immunodeficiency virus, HIV-1 proteinase at nanomolar concentration. In HIV infected cell culture they exhibit antiviral activity. We have analyzed the non infectious HIV particles produced in chronically HIV infected cell culture in presence of one of these inhibitors. The total production of virus particles was not substantially reduced in drug treated cultures, compared to non-inhibited control cultures, but the infectivity of these virus particles was reduced about 100 fold. The processing of gag and gag-pol protein precursor was inhibited; only borderline activity of reverse transcriptase (RT) could be detected in these particles and they contained nonprocessed gag precursor protein. Thin section electron microscopy of inhibitor-treated, HIV-infected cells revealed reduced viral cytopathogenicity and both inhibition of particle assembly and incomplete maturation of the particles formed. The HIV particles produced in the presence of the proteinase inhibitor were studded with envelope glycoprotein knobs and often comprised multiple budding regions, but were morphologically immature. PMID- 1929882 TI - [T cell clones and its application]. PMID- 1929881 TI - Subcellular localization of acidic and basic PR proteins in tobacco mosaic virus infected tobacco. AB - Infection of Samsum NN tobacco with tobacco mosaic virus (TMV) results in the induction of the synthesis of acidic and basic isoforms of many pathogenesis related (PR) proteins. By immunogold-electromicroscopy we have shown that PR proteins accumulate mainly in cells around the necrotic spots of TMV-induced lesions. The acidic chitinases, beta-(1,3)-glucanases and thaumatin-like proteins were found to accumulate in extracellular "pocket-like" vesicles while the basic chitinases were found in electron dense inclusion bodies in the vacuoles. These structures were not detectable in PR-containing leaves devoid of virus nor in healthy plants. PMID- 1929883 TI - [Effect of anti-idiotypic antibody on production of anti-DNA antibodies by splenocytes in lupus prone mice]. AB - It has been suggested that production of autoantibodies is regulated by idiotype antiidiotype network. In this study, we examined modulatory effect of the antiidiotypic antibody on the synthesis of anti-DNA antibodies by New Zealand black/New Zealand white F1 mice (B/W F1) splenocytes. The antiidiotypic antibodies were prepared by immunization of a monoclonal anti-DNA antibody derived from B/W F1 to rabbits. The prepared antiidiotypic antibody had specificity to the antigen binding site of anti-DNA antibodies. B/W F1 splenocytes were adjusted to 1 X 10(6) cells/ml and cultured in 1.0 ml aliquots in the presence of varying concentrations of the antiidiotypic antibody for 48 hours. The cells were then washed three times, resuspended in RPMI1640 containing 10% fetal calf serum and cultured again. On days 3 and 7 of the culture, the supernatants were harvested and secretion of anti-DNA antibodies was measured by ELISA. Production of anti-DNA antibodies by B/W F1 splenocytes was suppressed by pretreatment with the antiidiotypic antibody. When the concentration of antiidiotypic antibody was 1 microgram/ml, anti-DNA activity of the supernatants decreased 50%, compared with control on day 3, but the effect was reduced on day 7. The treatment of antiidiotypic antibody did not affect the proliferation and viability of B/W F1 splenocytes. The results indicated that anti-DNA antibodies synthesis were regulated by idiotype-antiidiotype network and could be manipulated by the antiidiotypic antibody. PMID- 1929884 TI - Increased smooth muscle cell proliferation by dimethylbenzanthracene is correlated to variations in activity of ornithine decarboxylase but not arylhydrocarbonhydroxylase. AB - Polycyclic aromatic hydrocarbons of cigarette smoke have been suggested to be involved in atherogenesis. After being converted to epoxides by monooxidases in the arterial wall the hydrocarbons may exert toxic or mutagenic effects on the smooth muscle cells (SMC). In a previous study we found that dimethylbenzanthracene (DMBA), an inducer of arylhydrocarbonhydroxylase (AHH), increased SMC proliferation and viability. In the present work we intended to study whether these effects were mediated by AHH. Alpha-naphtoflavone (ANF), a non specific AHH inhibitor, decreased SMC proliferation. The effects of ANF were totally counteracted by serum, partially by albumin and not at all by platelet derived growth factor. AHH activity was not detectable nor basally nor after induction in SMC, and this made us conclude that the effects of DMBA and ANF on SMC proliferation were not mediated by AHH. On the other hand the activity of ornithine decarboxylase was influenced by DMBA and ANF in parallel to proliferation, suggesting the involvement of this enzyme in the described DMBA effects on SMC proliferation. This mechanism might be of relevance for the pathogenesis of atherosclerosis especially in relation to cigarette smoking. PMID- 1929885 TI - "Cardiovascular risk factors in insulin dependent diabetes". AB - Diabetics have an increased risk of cardiovascular morbidity and mortality. Compelling evidence suggests that there is cause-effect relationship between alterations of serum lipids and lipoproteins, and atherosclerosis and coronary heart disease in non diabetic-population. Among insulin dependent diabetics, the prevalence of macrovascular disease is particularly increased in those with established clinical nephropathy and it has been partly attributed to concomitant hypertension and serum lipoprotein abnormalities. However, the effect of diabetic nephropathy and factors associated with it on Coronary Artery Disease (CAD) appears to be conditional. Many Patients in many studies did not have CAD despite a long duration of persistent proteinuria and renal failure There is the possibility that CAD is an outcome of a multistage process, and diabetes related conditions may accelerate progression through certain stage only. In that case, the pattern of appearance of CAD would be determined by the natural history of atherosclerosis rather than by duration of diabetes. The purpose of our study is to analyze retrospectively the incidence of CAD and its association with blood pressure, serum total cholesterol, HDL cholesterol, duration of diabetes, serum triglycerides and HbAlc in a cohort of insulin dependent diabetic patients without nephropathy. PMID- 1929886 TI - Heterogeneous responses of human endothelial cells to tumor necrosis factor with respect to growth inhibition. AB - The response of human arterial endothelial cells (ECs) to tumor necrosis factor (TNF) was compared to that of venous ECs. It was found that arterial ECs were more susceptible to TNF induced inhibition of growth and colony formation by TNF than venous ECs. In addition, synergistic effect of TNF with Interferon-gamma (IFN-gamma) was more evident in arterial ECs. Little difference, however, was identified in the characteristics of TNF receptors between arterial and venous ECs; the dissociation constant (Kd) was 0.35 nM and the number of receptors/cell was approximately 5,000. This indicates that different susceptibility of ECs to TNF is not due to these characters of TNF receptors. In conclusion, ECs are heterogeneous in the responsiveness to TNF depending on the sites of origins. PMID- 1929887 TI - Early therapy for Parkinson's disease. PMID- 1929888 TI - Trends in Parkinson's disease mortality in Italy. PMID- 1929889 TI - A commentary on steroid treatment in multiple sclerosis. PMID- 1929890 TI - Epidural steroids are safe and effective when given appropriately. PMID- 1929891 TI - Clinical correlates of white-matter changes on magnetic resonance imaging scans of the brain. AB - We report our observations on the clinical and radiologic correlates of changes in cerebral white matter based on 94 subjects undergoing magnetic resonance imaging in a prospective study of dementia. Periventricular hyperintensity occurred twice as often in patients with Alzheimer's disease as in healthy control subjects. Within the control group, the presence of periventricular hyperintensity correlated significantly with one measure of cerebral atrophy and with the presence of changes in the adjoining deep white matter. The significance of white-matter changes distinct from the ventricles (leuko-araiosis) remains unsettled. Leuko-araiosis on the magnetic resonance imaging scan, unlike its correlate on the computed tomographic scan, was not shown to relate to cognitive decline or to the presence of focal abnormalities on neurologic examination. This is likely to reflect the heterogeneity of the changes detected with magnetic resonance imaging and their limited extent in our subjects. PMID- 1929892 TI - Improved recognition of leukoaraiosis and cognitive impairment in Alzheimer's disease. AB - We identified 85 patients in a longitudinal study of dementia who had uncomplicated Alzheimer's disease and in whom computed tomography of the head and psychometric testing were conducted within a 6-month period following their entry into the study. Thirty-four patients (40%) had leukoaraiosis, which was disproportionately common in female patients (62% vs 15% in male patients). Analysis of covariance demonstrated a relative reduction of scores on the Extended Scale for Dementia in those patients who had leukoaraiosis, after adjusting for the confounding effects of age, sex, educational level, and duration of illness. Leukoaraiosis was also much more common in women, even after adjusting for the possible confounding effects of age, duration of illness, Extended Scale for Dementia score, and hypertension. Multiple regression analysis showed that leukoaraiosis accounted for 11.6% of the variance of the Extended Scale for Dementia scores. Leukoaraiosis, together with duration of illness, accounted for 18.2% of the variance. Leukoaraiosis is associated with a greater degree of cognitive impairment in patients with Alzheimer's disease. PMID- 1929893 TI - Cerebrovascular instability in a subset of patients with stroke and transient ischemic attack. AB - In six patients, we observed remarkably unsteady blood flow and indications of vasospasms on the arteriolar level in connection with episodes of focal cerebral ischemia. The patients originated from a prospective consecutive study of 53 patients with stroke and transient ischemic attack who had been examined by cerebral angiography and rapidly repeated regional cerebral blood flow measurements using the intracarotid xenon 133 method. In 47 patients, regional cerebral blood flow values, flow patterns, and clinical condition were stable during the repeated regional cerebral blood flow measurements. In six patients, pronounced regional hypoperfusion and hyperperfusion developed during the course of examination. In the hypoperfused regions, flow was transiently reduced to values consistent with ischemia, and in four of these patients this was accompanied by transient neurological deficits. The arteriogram and isotope angiograms ruled out spasms of large arteries or thromboembolism. A condition of cerebrovascular instability on the arteriolar level probably was induced by the examination procedure. These patients were hypersensitive to the provoking stimuli either habitually or as a consequence of previous ischemic accidents. It is suggested that in some patients with focal cerebral ischemia, the primary cause might be spasms of the smallest resistance vessels rather than thromboembolism. PMID- 1929894 TI - Gangliosides in cerebrospinal fluid in 'probable Alzheimer's disease'. AB - The concentrations of the four major brain gangliosides--GM1, GD1a, GD1b, and GT1b--were determined in cerebrospinal fluid from 43 patients with "probable Alzheimer's disease" and 19 healthy controls. Alzheimer's disease was divided into type I (with the memory disturbances and predominant cortical parietal symptoms that are characteristic of Alzheimer's disease) and type II (with general cognitive and mild confusional symptoms, with or without only mild parietal symptoms). The GM, concentration was significantly higher in patients with Alzheimer's disease type I than in those with Alzheimer's disease type II and age-matched controls, but did not differ significantly between patients with Alzheimer's type II and age-matched controls. As gangliosides are enriched in nerve cell membranes, preferentially in synapses, the findings suggest more severe degeneration of cortical nerve cells in patients with Alzheimer's disease type I than in those with Alzheimer's disease type II. PMID- 1929895 TI - Paired associate learning in senile dementia of the Alzheimer type. AB - A study was conducted to examine the potential explicit learning ability in senile dementia of the Alzheimer type (SDAT) as a function of (1) the difficulty of the to-be-remembered material and (2) the severity of the dementia. The Associate Learning task from the Wechsler Memory Scale was administered to healthy older adults and individuals with questionable, mild, and moderate SDAT. Individuals with SDAT showed poorer learning performance across trials than healthy older adults. Individuals with questionable and mild SDAT did show evidence for learning across trials for highly related paired associates. For unrelated-paired associates, however, only individuals with questionable SDAT showed some evidence for increased learning across trials. PMID- 1929896 TI - Monozygotic twins with seizures. Shared characteristics. AB - Eleven sets of monozygotic twins with idiopathic seizure disorders seen at Children's Hospital, Boston, Mass, were reviewed Nine twin pairs were concordant for seizures. A marked correlation in the precise timing of onset of seizures was found; three sets of twins had their first clinical seizures within a 24-hour period of one another. The clinical features of the seizures and the electroencephalographic patterns, including the location of focal discharges, were strikingly similar in the twin pairs. The significance of these findings in suggesting aberrant processes that may contribute to epileptic syndromes is discussed. PMID- 1929897 TI - Tremor at onset. Predictor of cognitive and motor outcome in Parkinson's disease? AB - We examined 46 male patients with idiopathic Parkinson's disease to see whether tremor at onset was as useful a predictor of benign clinical outcome as tremor predominance after several years. When we compared patients with tremor at onset (n = 27) with those whose disease began with brady-kinesia/rigidity (n = 9), or gait disorder (n = 10), we found no significant differences after a mean of 7 years in motor, cognitive, or affective status. Sixteen of the tremor-onset patients continued to have tremor predominance with minimal gait disorder after about 7 years. These tremor-predominant patients had significantly better motor outcome and somewhat better cognitive outcome than either tremor-onset patients who subsequently developed gait disorder (n = 11) or patients without tremor at onset (n = 19). Tremor predominance after several years appears to be a better predictor of a benign clinical course of Parkinson's disease than tremor at onset. PMID- 1929898 TI - Ultrasound findings in spontaneous carotid artery dissection. The value of duplex sonography. AB - Extracranial and transcranial Doppler and duplex sonographic findings in six patients with internal carotid artery dissection proven by angiography is reported. Extracranial Doppler analysis showed occlusion without a recordable signal from the internal carotid artery at any level or stenosis with accelerated flow in the high cervical segment. Transcranial Doppler findings demonstrated the hemodynamic consequences of the internal carotid artery occlusion or stenosis with collateral flow across the circle of Willis and also showed the dampened pulse wave of the middle cerebral artery ipsilateral to the dissection. In duplex sonography, the indirect signs indicating internal carotid artery dissection were a patent carotid bifurcation and proximal internal carotid artery segment but with no or only a short systolic flow signal. Atherosclerotic wall changes were absent, an important finding that suggests nonatherosclerotic stenosis or occlusion. Direct signs making the diagnosis likely were a tapering of the internal carotid artery lumen distal to the bulb, an irregular membrane crossing the vessel lumen, and the demonstration of a true lumen with flow and a false one without flow. While cerebral angiography is still considered the gold standard, ultrasound may become the primary modality for early diagnosis. Doppler and duplex examinations help to indicate angiography and are the methods of choice for follow-up investigations. They clearly demonstrate spontaneous recanalization with normalization of carotid circulation or, in case of persistent occlusion, improvement of collateral blood supply. Sequential examinations may prove helpful to determine the duration of anticoagulant treatment. PMID- 1929899 TI - High-intensity area in the deep white matter indicating hemodynamic compromise in internal carotid artery occlusive disorders. AB - We used positron emission tomography and magnetic resonance imaging to evaluate 16 patients with transient ischemic attacks or minor strokes and unilateral internal carotid occlusive disease, five with stenosis, and 11 with occlusion. Cerebral blood flow, cerebral metabolic rate of oxygen, oxygen extraction fraction, cerebral blood volume, and T2-weighted magnetic resonance images obtained at 1.5-T were analyzed. Irrespective of vascular disease, patients with a confluent high-intensity area in the middle centrum semiovale had substantially decreased cerebral blood flow and ratio of cerebral blood flow to blood volume in the middle cerebral artery distribution of the cortex, with a substantially increased oxygen extraction fraction. We concluded that the confluent high intensity area in the deep white matter region indicates hemodynamic compromise in the affected hemisphere in internal carotid artery occlusive disease. PMID- 1929900 TI - Automatic memory processes in patients with multiple sclerosis. AB - To better understand the nature of the memory deficit in patients with multiple sclerosis, we designed a study to compare automatic vs effortful memory processes. Forty-one patients with definite multiple sclerosis and 45 demographically matched normal control subjects were administered two tasks designed to assess both automatic (monitoring frequency and modality) and effortful (free and cued-recall) processing. Results indicated that patients with multiple sclerosis, as expected, were significantly impaired on memory measures requiring effort, but performed normally on automatic measures. Performance on the memory indexes did not correlate with self-reported depression. The implications of these findings for delineating the locus of the memory impairment in multiple sclerosis is discussed. PMID- 1929901 TI - Importance of intrathecal synthesis of IgD in multiple sclerosis. A combined clinical, immunologic, and magnetic resonance imaging study. AB - There is increasing evidence that soluble IgD has a certain role in the humoral immune response within the central nervous system. We report herein the results of a combined clinical, magnetic resonance imaging, and immunopathologic study to determine the clinical importance of intrathecal IgD synthesis. Intrathecal synthesis of IgD (detected through the calculation of index values) was studied in 64 patients with multiple sclerosis and in 50 neurologic control patients and normal subjects. Locally secreted IgD was detected in 30% of patients with clinically active multiple sclerosis, including two in whom magnetic resonance images of brain and spinal cord were normal and who had no evidence of intrathecal IgG synthesis. No intrathecal IgD production was detected in patients with clinically stable multiple sclerosis or those suffering from chronic progressive multiple sclerosis, while it significantly correlated with the interval from the last relapse and with the total duration of the disease process in patients with relapsing, remitting multiple sclerosis. Intrathecal IgD synthesis also correlated with the degree of cerebrospinal fluid pleocytosis and with the presence of free kappa and lambda light chain bands in cerebrospinal fluid. Present results supplement and expand earlier data and suggest that intrathecally secreted IgD is a putatively important part of the immune response in clinically active relapsing, remitting multiple sclerosis. PMID- 1929902 TI - Serologic evidence of Campylobacter jejuni/coli enteritis in patients with Guillain-Barre syndrome. AB - We performed serologic testing for Campylobacter jejuni in 17 consecutive patients with acute Guillain-Barre syndrome from the Boston, Mass area to compare the frequency of this preceding infection with the high rates reported from other areas of the world. The rate of seropositivity, 18%, was considerable, but it was lower than that reported in Australia. Moreover, all of our patients with definite serologic evidence of infection had severe enteritis before Guillain Barre syndrome, usually with the organism cultured from stool samples. Campylobacter enteritis is an important antecedent illness for Guillain-Barre syndrome but did not precipitate the disease without enteritis. PMID- 1929903 TI - Autonomic nervous function in progressive supranuclear palsy. AB - Autonomic nervous function was assessed in 11 patients with progressive supranuclear palsy, 26 patients with Parkinson's disease, matched for age, medications, disease severity, and disease duration, and 19 age-matched controls. Results of both parasympathetic (heart rate response to deep breathing and Valsalva maneuver) and sympathetic (blood pressure decrease on standing and increase on sustained handgrip) tests were abnormal in both patient groups. Abnormalities in the group of patients with progressive supranuclear palsy were similar to those in the group with Parkinson's disease but were more pronounced. Autonomic dysfunction may have to be considered a feature of progressive supranuclear palsy. PMID- 1929904 TI - Acute hemorrhagic leukoencephalitis. A successful recovery. AB - A 50-year-old woman developed acute hemorrhagic leukoencephalitis approximately 7 days after the onset of a benign respiratory infection. Mycoplasmal pneumonia was suspected because of Coomb's positive hemolysis, cold agglutinins, and sensitivity to erythromycin base but was not proved. Acute hemorrhagic leukoencephalitis was demonstrated by brain biopsy 24 hours after admission. The patient recovered without lasting sequelae following reduction of increased intracranial pressure by mannitol, hyperventilation, and phenobarbital and prolonged immunosuppression by plasmapheresis, steroids, and cyclophosphamide. PMID- 1929905 TI - Isolated congenital hemianopia caused by prenatal injury to the optic radiation. AB - Isolated congenital hemianopias are typically caused by developmental abnormalities of the occipital lobe cortex. We describe two patients with an incidental partial hemianopia associated with unilateral periventricular leukomalacia that was acquired prenatally. Magnetic resonance imaging scans suggest a late second or early third trimester unilateral cerebral ischemic event. PMID- 1929906 TI - Visual hallucinations and racing thoughts on eye closure after minor surgery. AB - Two hours after minor surgery under local anesthesia, a 67-year-old man developed vivid visual hallucinations that were present only when he closed his eyes. After lasting 4 hours, the hallucinations were succeeded by racing thoughts, lasting 2 hours, and then by illusionary movements of his body. The reaction was attributed to the effect of lidocaine. The case resembles one previously reported. PMID- 1929907 TI - Use of the disposable contact lens as a bandage contact lens. PMID- 1929908 TI - Topical timolol and serum lipoproteins. PMID- 1929909 TI - Laser photocoagulation for threshold retinopathy of prematurity. PMID- 1929910 TI - A multilens case. PMID- 1929911 TI - Aspirin and cataract. PMID- 1929912 TI - Zinc supplementation for macular degeneration. PMID- 1929913 TI - Vertical rectus muscle transposition surgery modified. PMID- 1929914 TI - Adjustable vertical rectus muscle transposition surgery. PMID- 1929915 TI - Grams of force. PMID- 1929916 TI - Complications of a hexagonal keratotomy following radial keratotomy. PMID- 1929917 TI - Corneal toxicity secondary to hydrogen peroxide-saturated contact lens. PMID- 1929918 TI - Cutaneous melanoma metastatic to the optic disc and vitreous. PMID- 1929919 TI - Contact lens-related Streptococcus viridans keratitis presenting as an epithelial defect. PMID- 1929920 TI - 16% RBRVS conversion factor to be reduced. PMID- 1929921 TI - Chloroquine retinopathy. PMID- 1929922 TI - Planning for federal support of eye research. PMID- 1929923 TI - Photorefractive keratectomy for astigmatism. Initial clinical results. AB - Excimer laser photorefractive keratectomy, developed to perform radially symmetric ablations to correct myopic or hyperopic refractive errors, was used to perform toric ablations designed to correct cylindrical errors. An expanding slit was used to flatten the cornea in the steep meridian. Four contact lens intolerant patients underwent this procedure for correction of astigmatism (two patients after penetrating keratoplasty, one patient after corneal ulcer, and one patient with naturally occurring high astigmatism). In each patient, surgery reduced the regular component of the astigmatism; residual irregular astigmatism limited spectacle-corrected acuity in one patient. All patients experienced a shift in spherical equivalent toward hyperopia. Toric ablations with the excimer laser appear to represent a promising strategy for the correction of compound myopic astigmatism that does not rely on creation of deep corneal incisions, excisions, or compression sutures. PMID- 1929924 TI - Trapezoidal keratotomy for the correction of naturally occurring astigmatism. AB - We performed trapezoidal keratotomy, consisting of combined nonintersecting semiradial and transverse incisions, in 64 eyes of 45 consecutive patients with naturally occurring astigmatism. The central clear zone diameter and number and length of transverse incisions were determined by the refractive error. Mean preoperative refractive astigmatism was 3.18 +/- 1.16 diopters (D) (range, 2.25 to 7.00 D). At the 1-year follow-up examination, the mean surgically corrected astigmatism determined by vector analysis was 3.70 +/- 1.50 D (range, 0.75 to 8.5 D), and the mean residual refractive astigmatism was 0.85 +/- 0.72 D (range, 0 to 4.0 D), with 64% of eyes having 1.00 D or less. The smaller the clear zone diameter, the greater the astigmatic correction. Longer transverse incisions produced more steepening of the secondary meridian. The operative complications included microperforation (5%), misalignment of surgical meridian (6%), encroachment on clear zone (5%), and inadvertent crossed incisions (11%). Trapezoidal keratotomy reduced naturally occurring astigmatism, but with only fair predictability and with some irregular astigmatism due to irregular wound healing. PMID- 1929925 TI - The ultrastructural defect in conjunctiva from a case of recessive dystrophic epidermolysis bullosa. AB - The predominant feature in the several forms of epidermolysis bullosa is the formation of cutaneous bullous lesions arising after minimal mechanical trauma. Ocular involvement has been noted as a complication. To our knowledge to date, only four investigators have correlated clinical eye disease with light microscopic findings. Ultrastructure of the ocular lesions has not been described previously. We present four cases of recessive dystrophic epidermolysis bullosa emphasizing their associated ocular complications. Diagnosis was confirmed by skin biopsy specimen and in one patient by demonstrating light and electron microscopic findings in eyelid skin. This tissue exhibited ultrastructural recessive cutaneous lesions; namely, bullous separation occurring below the basal lamina and absence of anchoring fibrils in both bullous and nonbullous areas. By electron microscopy, the conjunctiva in this patient exhibited an absence of clear anchoring fibrils that were numerous in control tissue. This defect may increase the susceptibility of the conjunctiva to minor mechanical trauma, resulting in the bullous and cicatricial changes seen clinically. PMID- 1929926 TI - Ocular findings associated with a rhodopsin gene codon 58 transversion mutation in autosomal dominant retinitis pigmentosa. AB - Eight members of a family with autosomal dominant retinitis pigmentosa were found to have a cytosine-to-guanine (C-to-G) transversion mutation in the second nucleotide of codon 58 of the rhodopsin gene, causing a substitution of the amino acid arginine for threonine. Five of these individuals were examined clinically. There was a distinct phenotypic expression of the gene defect within this family that included a regional predilection for pigmentary changes in the inferior and inferonasal parts of the retina, as well as field impairment predominantly in the superior hemisphere. Characteristic electroretinographic recordings and psychophysical threshold profiles also helped to identify this phenotype that, on a relative basis, causes less severe photoreceptor cell functional impairment than often occurs in other subtypes of retinitis pigmentosa. This report documents the association of a clinically recognizable phenotype in a family with autosomal dominant retinitis pigmentosa and a specific gene defect at the molecular level. PMID- 1929927 TI - Development of vision in retinopathy of prematurity. AB - Serial measures (range, two to eight) of preferential-looking grating acuities of 52 infants with retinopathy of prematurity were made. Group 1 patients (n = 11), who had little or no macular displacement, had normal preferential-looking acuity except for two who had mild acuity deficits. None of the group 2 patients (n = 12), who had dragged maculas, ever had normal acuity. On the average, their acuities, which ranged from 1 to 6 octaves less than normal, gradually increased at a rate not significantly different from normal. Group 3 patients (n = 29), who had undergone open-sky vitrectomy, had significantly lower acuity despite reattachment of the retina. PMID- 1929928 TI - Vitreous surgery for retinal detachment associated with choroidal coloboma. AB - We report the results of vitreous surgery in seven eyes with retinal detachments caused by retinal breaks at the margin of, or within, a choroidal coloboma. All seven eyes (100%) were reattached; visual acuities in five (71%) of the seven eyes improved from preoperative levels. Vitrectomy was combined with air-fluid exchange and endodrainage through preexisting retinal breaks or planned retinotomies in all but one of the cases. Part or all of the rim of the choroidal coloboma in six eyes underwent endophotocoagulation. The two eyes that did not experience postoperative visual improvement underwent intraoperative endolaser treatment 360 degrees around the optic nerve. If peripapillary endophotocoagulation is performed, especially through the papillomacular bundle, nerve fiber damage may occur and prevent visual recovery, despite retinal reattachment. For eyes with retinal detachment associated with choroidal colobomas involving the optic nerve, postoperative laser treatment through the papillomacular bundle may be preferable. PMID- 1929929 TI - Blind spot enlargement as a manifestation of multifocal choroiditis. AB - Enlargement of the blind spot without optic disc edema has been reported in patients with no other ocular findings (acute idiopathic blind spot enlargement) and in patients with multiple evanescent white dot syndrome. We describe three patients with multifocal choroiditis who developed acute symptomatic enlargement of the blind spot. All three patients were young women in excellent health. During the course of the blind spot enlargement, the appearance of the optic nerve remained normal. We demonstrate that acute enlargement of the blind spot without disc edema occurs in patients with multifocal choroiditis. This enlargement is likely due to peripapillary retinal dysfunction. We speculate on the association of multifocal choroiditis with acute idiopathic blind spot enlargement and multiple evanescent white dot syndrome. PMID- 1929930 TI - Pigmented paravenous retinochoroidal atrophy. Discordant expression in monozygotic twins. AB - We studied a 43-year-old woman affected with pigmented paravenous retinochoroidal atrophy and her unaffected monozygotic twin. The affected twin had stable visual acuity (20/25), typical fundus findings, markedly constricted visual fields, abnormal color vision, and an abnormal electroretinogram, all consistent with pigmented paravenous retinochoroidal atrophy. Results of examinations and studies in her twin were entirely normal. Fingerprinting for DNA performed on the twins strongly supported monozygosity. Our findings suggest that either our patient did not inherit pigmented paravenous retinochoroidal atrophy or that an unusual (nonmendelian) genetic mechanism occurred. PMID- 1929931 TI - Unilateral acute idiopathic maculopathy. AB - This is a report of nine patients who experienced sudden, severe, unilateral central vision loss following a flulike illness. Each patient had an exudative detachment of the macula. All patients experienced a spontaneous resolution of the acute macular manifestations with near-complete recovery of vision. A characteristic "bull's-eye" appearance in the macula persisted. The acute manifestations of the disorder did not recur in any of the patients during the period of follow-up. The constellation of findings was suggestive of an inflammatory disease of the retinal pigment epithelium, but a specific causative agent could not be identified. The acute clinical and angiographic features, the natural course, and the residual pigment epithelial derangement were not consistent with any previously described disorder. PMID- 1929932 TI - Molteno implants as a treatment for refractory glaucoma in black patients. AB - Eighty-two black patients with refractory glaucoma were treated with a single plate Molteno implant inserted in a single-stage procedure. A successful outcome (intraocular pressure less than or equal to 21 mm Hg with or without adjunctive medical therapy) was achieved in 72% of the patients with a mean follow-up of 30 months. Success was achieved in 23 (73%) of the 31 patients with open angle glaucoma, 20 (83%) of the 24 patients with either aphakic or pseudophakic glaucoma, 12 (67%) of the 18 patients with neovascular glaucoma, four (80%) of the five patients with uveitic glaucoma, and two (50%) of the four patients with congenital glaucoma. All but four patients required additional medical therapy. Visual acuities remained the same or improved in 21 (68%) of the 31 patients with open angle glaucoma, 11 (61%) of the 18 with neovascular glaucoma, 19 (79%) of the 24 patients with aphakic/pseudophakic glaucoma, three (75%) of the four patients with congenital glaucoma, and four (80%) of the five patients with uveitic glaucoma. Complications included hyphema (18%), "kissing" choroidal effusion (6%), blocked tube (8%), flat anterior chamber (12%), cataracts (5%), Tenon's cyst (encapsulated bleb) (17%), uveitis (7%), phthisis bulbi (5%), and erosion of the silicone tube (1%). PMID- 1929933 TI - Management of ocular penetration from injection of local anesthesia preceding cataract surgery. AB - We herein describe 12 patients who suffered penetration or perforation of the globe during injection of a local anesthetic before cataract surgery. Minimum follow-up was 6 months. Six eyes had a final visual acuity of 20/50 or better and an attached retina. Four eyes had an attached retina with a visual acuity of 20/80 to 2/200. Two eyes were anatomic failures because of a recurrent retinal detachment complicated by proliferative vitreoretinopathy. These cases show that retinal penetrations without retinal detachment may be treated effectively with photocoagulation. Vitreous surgery is recommended when the retinal penetration is associated with a retinal detachment. Eyes with a dense vitreous hemorrhage and a suspicion of a penetrating injury should either be followed up closely with echography or should undergo vitreous surgery since the extent of the injury cannot be determined. PMID- 1929934 TI - Corneal wound healing after 193-nm excimer laser keratectomy. AB - As part of a human trial of phototherapeutic keratectomy, we performed anterior keratectomy using excimer laser 193-nm ablation on patients with superficial corneal opacities. We examined the ultrastructural changes in the corneas of four patients who underwent penetrating keratoplasty 6 to 15 months after excimer laser ablation. The four cases included macular dystrophy, recurrent keratoconus in a graft, and corneal scarring (two eyes). Light microscopy showed epithelial thickening, absence of Bowman's layer, and superficial stromal scarring in the area of ablation. Ultrastructural study showed that the epithelial basement membrane had focal discontinuities. At the margin of the ablation superficial collagen bundles terminated abruptly in a steplike configuration. The anterior stroma was scarred, with loss of lamellar structure and an increase in number of fibrocytes. The laser-induced scar was 10 to 15 microns thick in the two eyes without a stromal scar before laser ablation. The stroma underlying the scarred areas and that in the untreated area appeared normal. Linear collagen-like fibers were present in the posterior aspect of Descemet's membrane. Laser-induced scarring may be an important factor in limiting visual improvement in patients undergoing phototherapeutic keratectomy. PMID- 1929935 TI - Large-cell acanthoma of the eyelid. Report of two cases. AB - We describe two cases of large-cell acanthoma that involved the skin of the upper eyelid. Patient 1 was a 71-year-old white man with a pale, well-demarcated papillomatous plaque of 3 months' duration. Patient 2 was a 62-year-old white man with a sharply demarcated plaque-like thickening of the pretarsal skin involving the eyelid margin of 2 years' duration. In both cases, the histopathologic findings were similar and showed an abrupt transition at the edge of the lesion between the normal epidermis and the acanthotic plaque, which displayed hyperkeratosis, hypergranulosis, and focal parakeratosis. The localized epidermal thickening showed enlarged keratocytes that appeared twice their normal size. To our knowledge, this is the first report of large-cell acanthoma involving the eyelid. PMID- 1929936 TI - Endothelial protection and viscoelastic retention during phacoemulsification and intraocular lens implantation. AB - Endothelial protection (measured by vital-dye staining and computerized planimetry) and viscoelastic retention during phacoemulsification with and without traumatic lens implantation were assessed in a rabbit model comparing four viscoelastics (Healon, Amvisc Plus, Occucoat, and Viscoat). No significant differences in cell damage were noted between unoperated on controls and groups that underwent atraumatic phacoemulsification with viscoelastic. Cell damage after traumatic lens insertion was reduced significantly by all four viscoelastics. Cell damage with and without traumatic lens implantation was significantly lower when viscoelastics were retained. Viscoat and Occucoat were significantly more likely to be retained than Healon. PMID- 1929937 TI - Larger optic nerve heads have more nerve fibers in normal monkey eyes. AB - The cup-to-disc ratio and the neural rim area are used to detect glaucoma damage to the optic nerve. Both parameters are dependent on the size of the optic disc and on the number of optic nerve fibers. We compared the size of the disc in fundus photographs with the number of nerve fibers in 25 normal monkey eyes. The number of fibers increased linearly with an increasing disc area. One must know the size of the optic disc to evaluate properly the cup-to-disc ratio or neural rim area. PMID- 1929938 TI - Comparison of Oculab Tono-Pen readings obtained from various corneal and scleral locations. AB - When estimating intraocular pressure in patients who are uncooperative or who have central corneal disturbances, the physician may find it either impractical or undesirable to place the small tip of a portable electronic applanation tonometer (Tono-Pen) over the central cornea. To gauge better the usefulness of Tono-Pen readings obtained from various locations, we compared such readings measured through the central cornea, midperipheral cornea, limbal cornea, and sclera of 15 cannulated eye bank eyes. Mean Tono-Pen readings from the midperipheral and clear limbal cornea did not differ significantly from central corneal readings over a 10- to 35-mm Hg range of intraocular pressures and were within +/- 2.4 mm Hg of mean central corneal readings. Mean readings taken from the sclera, however, were 8.8 to 17.0 mm Hg higher than mean central corneal readings over the 10- to 40-mm Hg range. We concluded that multiple noncentral corneal readings with the Tono-Pen provided a useful approximation of intraocular pressure, whereas scleral readings did not. PMID- 1929939 TI - Adherence of Pseudomonas aeruginosa to rigid gas-permeable contact lenses. AB - We examined the adherence of a human corneal isolate of Pseudomonas aeruginosa to unused rigid gas-permeable and hydrogel contact lenses. Adherence to rigid gas permeable lenses was greater than the adherence to hydrogels. The lower incidence of microbial keratitis associated with rigid gas-permeable lenses, as compared with hydrogel lenses, may be attributed to the more rigorous cleaning and disinfection possible for rigid gas-permeable lenses and/or patient noncompliance with complicated disinfection systems used with hydrogel lenses. PMID- 1929940 TI - Systemic mannitol increases the retinal adhesive force in vivo. AB - The effect of systemic mannitol administration on retinal adhesive force in the rabbit was investigated in vivo. The retinal adhesive force, 1 hour after intravenous mannitol injection (2.5 g/kg), was 45% greater than that in control eyes. When adhesiveness had been weakened by injecting Ca(2+)-free edetic acid (EDTA) solution into the subretinal space, intravenous mannitol still enhanced adhesion. Mannitol administration seems to be effective in enhancing retinal adhesion, even under the conditions where it has been weakened by other mechanisms. PMID- 1929942 TI - Leukemic iris infiltration in recurrent acute lymphocytic leukemia. PMID- 1929941 TI - Choroidal pneumocystosis. PMID- 1929943 TI - A technique for facilitated visualization and dissection of the vitreous base, pars plana, and pars plicata. AB - We describe a technique to facilitate visualization of the vitreous base, pars plana, and pars plicata during vitreous surgery. This technique takes advantage of an externally applied fiberoptic light source coupled with scleral depression to enable direct viewing of the ciliary processes and anterior vitreous base. No special instrumentation or alteration in pars plana vitrectomy techniques is required. We have used this technique to enhance anterior dissection during vitrectomy surgery in the aphakic and pseudophakic eye associated with proliferative vitreoretinopathy, diabetic retinopathy, epithelial down-growth syndromes, and postvitrectomy fibrin formation. PMID- 1929944 TI - Functional vs cosmetic ophthalmologic defects. PMID- 1929945 TI - Surgical technique in retinal detachment due to a macular hole. PMID- 1929947 TI - Symblepharon prevention. PMID- 1929946 TI - Transferrin receptor expression by retinal pigment epithelial cells in proliferative vitreoretinopathy. PMID- 1929948 TI - Branch retinal artery occlusion associated with Lyme disease. PMID- 1929949 TI - Successful prophylaxis of Clostridium perfringens endophthalmitis. PMID- 1929950 TI - Intraoperative suprachoroidal hemorrhage in congenital glaucoma associated with cutis marmorata telangiectatica congenita. PMID- 1929951 TI - AMA responds to RBRVS with grassroots campaign. PMID- 1929952 TI - DNA testing for retinoblastoma. PMID- 1929953 TI - Seven-millimeter medial rectus recessions and large-angle esotropia. PMID- 1929954 TI - Photocoagulation for ischemic central retinal vein occlusion. Central Vein Occlusion Study. PMID- 1929955 TI - Retinal vascular abnormalities in patients with coarctation of the aorta. AB - Pulsatile three-dimensional retinal arteriolar tortuosity has been previously reported in about 50% of patients with coarctation of the aorta. In a contemporary series of 20 patients with coarctation of the aorta, none exhibited this characteristic retinal vascular abnormality. Our findings suggest that the retinal vascular abnormalities in patients with coarctation of the aorta represent secondary hemodynamic changes. The prevalence of these abnormalities may be decreasing because of earlier surgical repair of coarctation. PMID- 1929956 TI - Class II major histocompatibility complex on melanocytes of Vogt-Koyanagi-Harada disease. AB - The eyes obtained from two Japanese autopsy cases of patients with Vogt-Koyanagi Harada disease were immunohistochemically examined. Both patients, a 63-year-old woman and a 68-year-old man, were clinically and histologically diagnosed as having Vogt-Koyanagi-Harada disease. Immunohistochemically, the choroidal infiltrate was composed predominantly of T lymphocytes with a larger proportion of helper/inducer T cells than suppressor/cytotoxic T cells and it also included activated lymphocytes expressing CD26 and CD25 antigens. Class II major histocompatibility complex was expressed in the choroidal melanocytes as well as in the endothelium of the choriocapillaris. Depositions of complement, however, were focally noticed in the choroid. Our results indicate that the cell-mediated immune process plays an important role in the development and progression of Vogt Koyanagi-Harada disease, while choroidal melanocytes appear to play a pathogenic role in this disease. PMID- 1929957 TI - Reassembly of the corneal epithelial adhesion structures following human epikeratoplasty. AB - Ten epikeratoplasty lenticules removed after surgery were obtained for immunohistochemical and electron microscopic analysis to determine the pattern of re-formation of corneal epithelial adhesion structures. Antibodies to laminin and type VII collagen were used to determine the presence of basement membrane and anchoring fibrils, respectively. Electron micrographs were used to determine the percentage of basal cell membrane occupied by hemidesmosomes, the area of basal lamina per 100 microns of basal cell membrane, and the average maximum depth of penetration of anchoring fibrils into the stoma. Nine normal corneas served as controls. Compared with normal corneas (24.5% of basal cell membrane occupied by hemidesmosomes; 32.0 microns 2 basal lamina per 100 microns of basal cell membrane), lenticules removed for optical reasons had near-normal hemidemosomes as early as 10 weeks following surgery (mean, 20.3%). The area of basement membrane was reduced (16 microns 2 basal lamina per 100 microns of basement cell membrane). During the course of 2 to 3 years, irregularities and duplications of the basement membrane were noted. Compared with normal corneas, the two lenticules removed for persistent defects had a marked reduction of hemidesmosomes and basement membrane present under epithelium at 3 and 4 weeks (9.6% of basal cell membrane occupied by hemidesmosomes and 13.6 microns 2 basal lamina per 100 microns of basal cell membrane, and 5.4% of basal cell membrane occupied by hemidesmosomes and 7.2 microns 2 basal lamina per 100 microns of basal cell membrane, respectively. PMID- 1929958 TI - Antioxidant enzymes in the aging human retinal pigment epithelium. AB - The antioxidant enzymes catalase and superoxide dismutase have integral roles in controlling reactive oxygen radicals that can harm cells. In the present study, we quantitated catalase activity in retinal pigment epithelium, retina, iris, and vitreous from human donors. To our knowledge, our results represent the first quantitation of catalase activity in human retinal pigment epithelium and show six-fold greater catalase activity in retinal pigment epithelium than in other ocular tissues analyzed (P less than .0001). To investigate whether aging or macular degeneration affects retinal pigment epithelium catalase or superoxide dismutase activities, we measured enzyme levels in retinal pigment epithelium from donors 50 to 90 years of age with and without evidence of macular degeneration. Superoxide dismutase activity showed no significant correlations with aging or macular degeneration, while catalase activity decreased with age (P less than .02) and macular degeneration (P less than .05) in both macular and peripheral retinal pigment epithelium. PMID- 1929959 TI - Fungal endophthalmitis. An experimental study with a review of 17 human ocular cases. AB - Pseudallescheria boydii is an opportunistic fungus that is histologically indistinguishable from Aspergillus fumigatus. Pseudallescheria boydii has been reported to cause endophthalmitis, orbital cellulitis, and corneal ulceration and is, thus, important to the ophthalmologist. A clinical review of 17 patients with P boydii ophthalmic infections is presented. In addition, animal models of endophthalmitides caused by A fumigatus and P boydii were created and compared. Dutch-Belted rabbits used for the experimental models were immunosuppressed with methylprednisolone acetate (Depomedrol). Exogenous and endogenous models of P boydii endophthalmitis were created in immunocompetent and immunosuppressed animals. An exogenous model of A fumigatus endophthalmitis was created in immunocompetent and immunosuppressed animals for comparison. The clinical and histopathologic features of A fumigatus and P boydii endophthalmitis are indistinguishable in the immunocompetent and immunosuppressed exogenously infected rabbits. Endogenous P boydii endophthalmitis has a similar fundus appearance to that caused by Nocardia asteroides. PMID- 1929961 TI - Age-related macular degeneration and ghost cell glaucoma. PMID- 1929960 TI - MK-507 (L-671,152), a topically active carbonic anhydrase inhibitor, reduces aqueous humor production in monkeys. AB - An investigation was carried out to determine the mechanism by which MK-507 (L 671,152), a water-soluble inhibitor of human carbonic anhydrase II in vitro, reduces intraocular pressure when applied topically to monkey eyes. Intraocular pressure, tonographically measured outflow facility, and fluorophotometrically determined aqueous humor flow were measured before and after therapy in eight normal cynomolgus monkeys. Fifty microliters of 2% MK-507 was instilled in one eye and diluent in the contralateral eye. Baseline values for intraocular pressure, outflow facility, and aqueous humor flow were similar in the drug treated and diluent-treated control eyes. After therapy, intraocular pressure was significantly (P less than .05) reduced from 1 to 7 hours (eg, 14.0 +/- 1.0 and 15.9 +/- 0.9 mm Hg [mean +/- SEM], treated and control eyes, respectively, at 3 hours). Outflow facility was not significantly (P greater than .40) changed at 3 hours, and aqueous humor flow measured over 5 hours was significantly (P less than .05) reduced (38%) in treated (0.9 +/- 0.1 microL/min) as compared with control eyes (1.5 +/- 0.1 microL/min). The results suggest that MK-507 reduces intraocular pressure by decreasing aqueous humor production. PMID- 1929962 TI - Removal of the eye with socket ablation. A limited subtotal exenteration. AB - Following enucleation or evisceration, the wearing of a prosthetic eye may be impractical, impossible, or undesirable. We describe herein 10 patients for whom a prosthesis was not feasible and who therefore underwent removal of the eye with extirpation of the conjunctiva, tarsi, and lid margins, followed by lid closure. The procedure as originally described is suitable for a wide range of disorders. Modifying the technique to incorporate simultaneous removal of the conjunctiva, tarsi, and lid margin together with enucleation of the globe permitted the use of the operation in the treatment of patients with ocular and conjunctival surface malignant neoplasms. Although the procedure does not replace simple enucleation of the globe or exenteration of the orbit, it is useful under certain circumstances. PMID- 1929963 TI - Introducing the Reiss punctal punch. AB - We describe a new instrument specifically designed to perform a "wedge" punctoplasty. The Reiss punctal punch was designed to be an enhancement of the one-snip punctoplasty by providing greater uniformity and improved tear access to the punctum via an excised posterior tissue wedge as well as inhibiting reapproximation of the cut edges leading to recurrent punctal stenosis. PMID- 1929964 TI - Sophia Heathcote vindicated. PMID- 1929965 TI - A letter from Romania. PMID- 1929966 TI - Practice dilemmas for ENs. PMID- 1929967 TI - SIDS research breakthrough. PMID- 1929968 TI - Nurse and the law. Tampons and toxic shock syndrome. PMID- 1929969 TI - The third age. Zealotry. PMID- 1929970 TI - Simvastatin. PMID- 1929971 TI - Diagnosis of primary hyperparathyroidism. PMID- 1929972 TI - Diagnosis of ruptured diaphragm following blunt trauma: results from 85 cases. AB - Between 1975 and 1990, 85 patients with diaphragmatic rupture following blunt trauma were treated at the Royal Brisbane and Princess Alexandra Hospitals, Brisbane. There were 65 on the left, 17 on the right and three were bilateral. Road trauma was the cause in 88% of cases. In the first 48 h the diagnosis was made by chest X-ray in 51 patients, laparotomy in 22, autopsy in two, emergency room thoracotomy, ultrasound and pneumoperitoneum each in a single patient. Seven patients (8%) had delay in diagnosis greater than 48 h ranging from 6 days to 6 months. Diagnosis was subsequently made by pneumoperitoneum (3), chest X-ray (1) and exploratory thoracotomy (1). Two patients presented with a strangulated diaphragmatic hernia 3 and 6 months following an acute admission with blunt chest trauma and urological trauma respectively. During the study period a further five patients presented with an obstructing diaphragmatic hernia. Sixteen patients died (19%), fifteen from associated injuries and one related to the diaphragmatic repair. Ruptured diaphragm should be suspected in patients with severe chest trauma, particularly those requiring positive pressure ventilation, patients with intra-abdominal injuries and those with pelvic fractures. Early recognition and repair results in low morbidity and mortality. Measures that confirmed the diagnosis in patients with delay included repeated chest X-rays and pneumoperitoneum. PMID- 1929973 TI - Management of traumatic parotid sialoceles and fistulae: a prospective study. AB - A prospective study of 13 patients with traumatic parotid fistulae or sialoceles showed that 54% resolved on conservative management within a 3 week period. Those that did not were treated by internal surgical drainage with uniform success, although care had to be taken with the catheter placement. No factors predictive of those cases requiring operative drainage other than failure of conservative management were found. PMID- 1929974 TI - Locally advanced (stage III and IV) head and neck cancer: Westmead Hospital experience. AB - Two hundred and fifty-one patients with Stage III and IV (UICC staging system) squamous cell cancers of the oral cavity, oropharynx, hypopharynx and larynx were assessed between January 1980 and December 1988 at Westmead Hospital. Of these, 50 patients received palliative treatment or were not treated and the remaining 201 patients received treatment with curative intent by various combinations of radiotherapy, surgery and chemotherapy. Thirty-nine operable cases were entered into a multimodality protocol initiated in April 1985, which consisted of induction chemotherapy (cisplatin 100 mg/m2 i.v. day 1, 5-fluorouracil 1000 mg/m2 per 24 h i.v. days 1-5, q3w x 2) followed by surgery and postoperative radiotherapy. The median follow-up for all 251 patients was 57 months. Actuarial 3-year survival rate for all 201 patients receiving radical treatment was 48% (Stage III 66%, Stage IV 36%; P less than 0.001). Overall actuarial local and nodal control rates at 3 years were 67% and 69%. Thirty-two of 201 patients (16%) developed distant metastases at a median time of 11 months. Twenty-one patients (10%) had a previous or subsequent second primary cancer. In the group of 39 protocol patients, overall actuarial survival, local and nodal control rates are 68%, 77% and 73% at 3 years. A group of 22 'protocol' patients was compared with a group of 22 patients treated prior to commencement of the protocol, matched as closely as possible on the basis of site, stage, age, sex and ECOG status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929975 TI - Synchronous combined oesophagectomy: a review of 20 cases. AB - Twenty patients with carcinoma of the oesophagus treated by a modification of the Ivor Lewis oesophagectomy using two surgeons working synchronously were reviewed. All the patients had carcinomas of the middle or lower thirds of the oesophagus. The median age was 68 years. There were 17 males and 3 females. Average total operating time was 3 h 40 min. There was one peri-operative death. The median length of stay was 15 days. The synchronous combined approach to oesophagectomy has advantages, which are discussed, similar to synchronous combined abdomino perineal resection of the rectum. PMID- 1929976 TI - Leiomyoma of the oesophagus. AB - Leiomyoma of the oesophagus is an uncommon lesion but should be considered in the differential diagnosis of younger patients presenting with dysphagia or mediastinal mass. This report deals with the management of 14 cases of leiomyoma seen during a 12 year period. PMID- 1929977 TI - Chiari osteotomy in the adult: a long-term follow-up study. AB - For almost 20 years the Chiari pelvic displacement osteotomy has been used as a method of providing cover to the femoral head in cases of acetabular dysplasia. The osteotomy is one of a number of procedures that have been used in an attempt to prevent the early development of secondary osteo-arthritis and the need for total hip replacement. More recently, the operation has been undertaken in cases where there is already some arthritic change. This long-term review of 18 Chiari operations shows that the procedure was successful in cases of acetabular dysplasia where there was minimal subluxation of the femoral head (i.e. with Shenton's line still intact). In more advanced cases where there was significant subluxation (i.e. with Shenton's line broken by more than 1 mm) and even early arthritic changes, the results were poor. It is concluded that the operation may be of value as an almost 'prophylactic' procedure but that it is of no value as a so-called 'salvage' procedure. PMID- 1929978 TI - Principles of organ preservation: research in a surgical department. PMID- 1929980 TI - 'Mrs L.'s case': a celebrated South Australian surgical case. AB - This paper concerns a dispute at the Adelaide Hospital in September 1896 between Professor Archibald Watson, Pathologist, Honorary Consulting Surgeon and sole remaining University teacher at the hospital, and Alexander Disney Leith Napier, who had arrived from England to fill the place of the honorary surgeons who had resigned from the hospital. Watson accused Napier of incompetence in his management of 'Mrs L.', who died after a femoral hernia operation. Mrs L had a form of internal hernia causing intestinal obstruction, whereas all the medical attendants, including Watson, originally thought an old femoral hernia was the cause of her illness. By fortuitous coincidence the operation on the femoral hernia could have cured the internal hernia if the band of omentum attached to the femoral hernia had been divided. Watson became aware of the band at the post mortem and then asserted that the operation should have taken it into account. Napier complained to the Board of the Hospital, alleging that Watson had misrepresented the facts when he conducted the post-mortem on the patient and that he was disloyal to the hospital. The Board found the complaint proved and invited Watson to resign; he declined and was dismissed. Undaunted, Watson circulated a privately printed pamphlet (entitled 'Mrs L.'s case'), which re stated the events of the case and graphically described his post-mortem findings. It was submitted to the Chairman of a Select Committee of the Legislative Council of South Australia established to review the running of the hospital. The Committee recommended the setting up of a Royal Commission but the Government let the matter lapse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1929979 TI - Postoperative fatigue: a prospective physiological study of patients undergoing major abdominal surgery. AB - We attempted to define the site of muscle action accounting for the apparent muscle weakness occurring with postoperative fatigue. A model of the normal pathway of muscle contraction is presented. A series of studies, designed to separate the elements of the pathway, was performed on 38 patients undergoing major abdominal surgery. Central fatigue was measured with Christensen's analogue, voluntary strength by grip strength, perceived effort by grading the difficulty of a set work load, involuntary muscle function by ulnar nerve stimulation, and muscle bulk represented by total body nitrogen, measured by in vivo neuron activation analysis. Fatigue increased for the first 2 weeks after operation, was back to pre-operative levels within 1 month, and improved further at 3 months. Grip strength fell after operation and returned to pre-operative levels within 3 months. Perceived effort rose after operation and returned to pre operative levels by 3 months. Involuntary muscle function was unaffected by operation. Similarly, total body nitrogen fell in the first 2 weeks after operation but was improved on baseline levels at 3 months. However, there was no consistent correlation between the movement patterns of any of the muscle parameters and fatigue. The results suggest that fatigue after surgery is not accompanied by any muscular defect, and that the apparent muscular weakness is probably a secondary phenomenon to the central fatigue. PMID- 1929981 TI - Thoracic intramedullary haematoma as a complication of warfarin: case report and literature review. AB - Spontaneous intraspinal haematomas due to anticoagulants are uncommon, and usually extradural or subdural. Intramedullary haematomas are particularly rare, and only two case reports were found in the literature. We report a case of a thoracic intramedullary haemorrhage in a 61 year old man who had been commenced on warfarin 1 month previously, following aortic valve replacement. The literature is reviewed and reversal of warfarin effects, imaging and recommendations for treatment are discussed. PMID- 1929982 TI - Orbital blowout fracture from hydrostatic pressure. AB - This case report describes an orbital blowout fracture due to hydrostatic pressure from a high-diving accident. Also described are the velocities encountered in this case. PMID- 1929983 TI - Two cases of primary bacterial peritonitis presenting with a tender hernia. PMID- 1929985 TI - Traumatic chylothorax: a case report. AB - A case of traumatic chylothorax following a motor vehicle accident is presented. This is a rare injury following thoracic trauma and is associated with a high mortality and morbidity. Mechanisms of injury to the thoracic duct are described. A management strategy is suggested, which initially entails a trial of conservative therapy of adequate drainage, total parenteral nutrition (TPN) and total gut rest. If significant chyle losses persist after 2 weeks, surgery is indicated, as immunological factors may complicate recovery. The recommended surgical technique is transthoracic duct ligation directly or at the hiatus. PMID- 1929984 TI - Pre-colonoscopy bowel preparation intolerance: a sign of upper gastrointestinal pathology. AB - Severe vomiting and abdominal pain were precipitated by polyethylene glycol-based gut lavage (PEG) in two patients out of 585 referred for colonoscopy in a 2 year period. Both patients had primary adenocarcinoma of the large bowel but both were also found to have gastroduodenal problems severe enough to need surgical treatment. Both cases are presented. PMID- 1929986 TI - Resection for congenital tracheal stenosis. AB - A case of congenital tracheal stenosis is reported. The diagnosis was made on plain X-ray, tomography and computerized axial tomography of the trachea when the child was 8 years old. The operative approach was via a median sternotomy and anaesthesia maintained with dual simultaneous ventilation of the right upper lobe bronchus and distal trachea. Histology of the stenotic area revealed the cartilaginous rings to be completely encircling the trachea. PMID- 1929987 TI - Use of phenytoin to treat horses with Australian stringhalt. AB - Five horses with Australian stringhalt were treated with 15 mg/kg phenytoin orally for 2 weeks. During the second week of the trial, 3 of the horses were given an additional dose of 10 mg/kg phenytoin. The response to treatment was clinically assessed by grading the severity of the gait abnormality at the walk, trot, turning and backing twice daily. There was a significant (P less than 0.05) improvement in the gait abnormality when pre-treatment values were compared with the mean of the last 3 assessments before treatment stopped. When reassessed 2 weeks after treatment ceased, there remained a significant (P less than 0.05) improvement compared with pre-treatment values at the trot and on backing, but not at the walk or turning. Surface electromyographic recordings were made weekly from the long digital extensor muscle, and there was a change to a near normal recording by the end of treatment. Plasma phenytoin concentrations were monitored during the trial, and the dose rates used achieved a steady state with a mean plasma level of 37 +/- 7 mumol/l. There was wide variability between plasma concentrations in different horses, although there was no difference in absorption between administration of the phenytoin as a paste, or when it was mixed in the feed. Although mild tranquilization was seen after treatment, there were no clinical, haematological or biochemical signs of toxicity from the phenytoin therapy. PMID- 1929988 TI - Diethylstilboestrol--historical background and current regulatory status. AB - Diethylstilboestrol is a non-steroidal orally active oestrogen that in the past has been widely used in a variety of conditions in both medical and veterinary fields. In recognition of potential systemic availability to man of DES in the tissues of treated food-producing animals, together with an understanding of the potential teratogenic and carcinogenic toxicity of DES in man, the veterinary use of DES has been restricted to oral use in small animals only. Use of DES is prohibited in all food-producing animals. PMID- 1929989 TI - Diethylstilboestrol--clinical pharmacology and alternatives in small animal practice. AB - Diethylstilboestrol is currently only available in Australia for oral use in dogs and cats. As an orally and systemically active non-steroidal oestrogen, DES has been widely used in small animal veterinary medicine for a variety of indications. A review of the literature reveals that many of the recommendations for use are founded on anecdotal or unreported clinical observations. While many of the uses may be valid, accurate determinations of optimum dosing regimens have not been defined. This is especially unfortunate in view of the potential toxicity of DES to small animals. Nevertheless, particularly in cases of low-dose intermittent administration, oral DES appears indicated at least until data on alternative safe and effective interventions become available. PMID- 1929990 TI - Photosensitisation and crystal-associated cholangiohepatopathy in sheep grazing Brachiaria decumbens. AB - Two outbreaks of photosensitivity and jaundice in sheep grazing the grass, Brachiaria decumbens. In West Java in 1983 and 1983 and 1990 are described. Aggregates of acicular clefts and crystals were present in bile canaliculi, bile ducts, Kupffer cells, hepatocytes and in kidney tubules. The number of crystals increased with the length of exposure to the plant and sheep that died had the largest accumulations. These crystalline structures have been reported before in this syndrome, but are similar to those seen in Tribulus terrestris and Panicum spp toxicities. PMID- 1929991 TI - Anasarca and myopathy in ostrich chicks. AB - Twenty ostrich chicks that died at, or within, 1 week after hatching were examined from 7 farms with poor (43 to 75%) hatchability. All chicks had anasarca and 15 had mild, generalised, acute degenerative changes in the complexus and pelvic limb muscles. One had fibrinoid degeneration of arterioles. Biochemical examinations produced no evidence of deficiencies of selenium, vitamin A or vitamin E. The syndrome was related to high relative humidity during incubation. Malpositioning also was a cause of embryo mortality. PMID- 1929992 TI - Assessment of the potential toxicity of a poison for rabbits, pindone (2-pivalyl 1, 3 indandione), to domestic animals. AB - The toxicity of pindone, a rabbit poison, to horses, cattle, goats, chickens, dogs and cats was investigated, using extension of prothrombin time (PT) as an index of poisoning. The daily dose of pindone, administered for 5 days, ranged from 0.3 mg/kg for dogs to 2.5 mg/kg for chickens. This range of dose rates was considered to be indicative of the worst possible case that could arise following a campaign of baiting for rabbits. Although significant elevations in PT (more than double baseline values) were noted in all species other than horses, clinical signs of anticoagulant poisoning were not observed in any of the species tested. From the observed PT, cattle and cats appeared to be the most susceptible, and horses the least susceptible, to pindone toxicity. The half lives of the elevated PT were calculated as 3.1 days for cattle, 2.8 days for goats and chickens, 1.9 days for horses and dogs and less than one day for cats. It is proposed that these half-lives can be used as a guide for determining the duration of treatment of pindone-affected animals. PMID- 1929993 TI - Epitheliocystis in the leafy sea-dragon. PMID- 1929994 TI - Sterility in a poll Hereford bull associated with the 'tail stump' sperm defect. PMID- 1929995 TI - Career aspirations of emerging veterinarians. PMID- 1929996 TI - Two cases of epidermotropic lymphoma in dogs. PMID- 1929997 TI - Dog attacks on children: report from two major city hospitals. PMID- 1929998 TI - Listeria in cooked chicken, pate and mixed smallgoods. PMID- 1929999 TI - Skeletal myopathy induced by monensin in adult turkeys. PMID- 1930000 TI - Antigenic competition following reconstitution of canine vaccines. PMID- 1930001 TI - Vesicopustular eruptions in the neonate. PMID- 1930002 TI - Sunscreen use on Queensland beaches. AB - The prevalence of use of sunscreens was assessed in an environment of high ultraviolet (UV) exposure by surveying 117 males and 126 females on two Queensland beaches. Using a questionnaire, information was obtained about their application of sunscreen on the day of participation in the study, thus eliminating recall error. It was found that 71% of the female and 68% of the male beach-goers sampled had applied sunscreen, 47% of which had the maximum Sun Protection Factor (15+) rating. There was no significant association found between usage and either skin colour or socio-economic status. Although 88% used a waterproof formulation, only 61% reapplied the sunscreen directly after swimming. Sunscreen was not applied to all exposed body parts, with over half of the subjects neglecting ears and lower limbs. Reported major reasons for use were to avoid skin cancer (44%), and to avoid sunburn (43%). The results of this study can assist in evaluating the effectiveness of present sun-protection campaigns in the short term. PMID- 1930003 TI - Lentinginous dysplastic naevi in the elderly: a potential precursor for malignant melanoma. AB - Seventy-seven skin biopsies diagnosed histologically as lentiginous junctional naevi from individuals aged over 60 years were reviewed. Seventy-three specimens showed a primarily nested pattern with disordered arthitecture concentrated within the rete ridges conforming to the pathology of a lentiginous dysplastic naevus. In 28 biopsies this was combined with a melanoma in situ. The latter was reflected by a focal loss of the rete ridge system, confluent melanocytic hyperplasia and single cell invasion of the epidermis by atypical malanocytes. Four biopsies showed lentiginous junctional naevi with only isolated naevus cell nests without a disordered architecture or cellular atypia. Thirty-seven of the 57 naevi in men were located on the back in contrast to 5 of the 20 women. In women the lower limb was the most frequent site with 8 of the 20 lesions originating at this site in contrast to 1 of the 57 men. The pathological diagnosis of dysplastic lentiginous naevi in the elderly needs to be recognised as having a high association of melanoma-in-situ changes. PMID- 1930004 TI - Primary localised cutaneous amyloidosis in Malaysians. AB - A review of consecutive biopsies from 85 Malaysian patients with primary localised cutaneous amyloidosis (PLCA) revealed 63 with papular amyloidosis (PA) and 22 with macular amyloidosis (MA). PLCA appeared to affect the Chinese more frequently than the other major ethnic groups but MA was more common than expected among the Indians. Of patients with PA, one had systemic lupus erythematosus, one scleroderma and in another, connective tissue disease was suspected. MA was not found to be associated with any other disease. Histologically, PA differed from MA by the larger size of amyloid deposits in the papillary dermis. There was no difference in their tinctorial and immunohistochemical characteristics. Deposits were permanganate-resistant and negative for AA protein, immunoglobulin light chains and keratin. A few cases exhibited positively for cytokeratin. Strong immunoreactivity for AP protein was observed. PA and MA appear chemically similar and are likely to be of epidermal origin. PMID- 1930005 TI - A survey of risk factors for adverse reactions to intravenous contrast media. PMID- 1930006 TI - Iohexol, ioxaglate and iopamidol in coronary angiography. A double-blind comparative study of 300 patients. AB - A randomized, double-blind study was carried out in 300 consecutive coronary angiography examinations to investigate the clinical safety of three low osmolar contrast media, iohexol 300, ioxaglate 320 and iopamidol 300, and the electrocardiographic changes that occurred with them. The ECG from electrode V5/V6 or AVF and intra-arterial pressure were monitored continuously, and recorded before and after the first contrast injections into the left and right coronary arteries. Of the variables tested, no statistically significant changes occurred in systolic arterial pressure, PR interval or ventricular extrasystole. The QT interval increased in the ioxaglate group (p = 0.001). Heart rate decreased in all groups, but slightly less in the ioxaglate group than in the iopamidol group (p = 0.02). The ST segment depression (mean 0.67m) was more marked in the ioxaglate group than in the other treatment groups (p = 0.0001) during right coronary angiography. The same characteristics, but less marked, were observed during left coronary angiography, the ioxaglate group (mean 0.251mm) differing from the iopamidol group (mean 0.050mm) (p = 0.04). No significant difference in severe adverse reactions were detected between these groups (ioxaglate 1, iopamidol 1). Ioxaglate produced mild side effects (nausea, vomitus, urticaria) in 16% of the patients, the other two contrast agents producing side effects in 1%. PMID- 1930007 TI - Supratentorial tumours. Part III: Tumours of non neuroglial cells (1). PMID- 1930008 TI - Supratentorial tumours. Part IV: Tumours of non neuroglial cells (2). PMID- 1930009 TI - MRI of lumbar and sacral plexus nerve sheath tumours. AB - Seven patients with peripheral nerve sheath tumours affecting the lumbo-sacral plexus were examined with MR imaging utilizing a 1.5T magnet and spin echo pulse sequences. The majority of tumours were homogeneous in signal intensity and isointense with adjacent muscle on T1 weighted images and showed markedly increased signal intensity on T2 weighted images with central areas of relatively low signal intensity. An attempt to obtain a pathological correlation with the areas of low signal on T2 weighted images was unsuccessful. The use of Gadolinium DTPA in one patient resulted in irregular enhancement of both a neurogenic sarcoma and smaller neurofibromas. The multiplanar imaging capabilities, high soft tissue contrast, non-invasiveness, lack of ionizing radiation and the characteristic appearance of neural tumours makes MR ideal for imaging these lesions. PMID- 1930010 TI - Is what you see what you get? Breast specimen handling re-visited. AB - Specimen radiography is already established as an essential adjunct to excisional biopsy of mammographically detected abnormalities. Two methods of specimen sectioning following the initial specimen radiograph are described. The techniques were devised to identify the lesion accurately in the specimen for subsequent pathological analysis. They have been tailored to suit the differing facilities at two Breast Screening Centres. The methods highlight the desirability of a cooperative multidisciplinary approach to the management of breast disease. They underline the importance of radiological localization of the lesion; not only for the surgeon, but also for the pathologist. PMID- 1930011 TI - Analysis of 308 localisation breast biopsies in a New Zealand hospital. AB - The authors have reviewed 308 localisation biopsies performed on nonpalpable breast lesions between 1986 and 1990. The initiating mammogram, specimen radiograph, radiologists' reports and histology reports have been analysed with respect to the nature of the mammographic lesion, patient age, breast parenchymal pattern and histologic diagnosis. The overall malignant biopsy rate was 28%. Malignancy was found in 67% of biopsies for architectural distortion, 27% for calcification and 25% for a mass lesion. Masses if malignant proved to have an invasive component in the majority of cases (29/33). Calcification if malignant was more often in situ carcinoma (25/44). 29% of malignant biopsies were in women under the age of 50 and approximately half of these had an invasive component. The histologic nature of benign lesions is presented with identification of those with proliferative breast disease. The results are compared with those of other recently published series. Implications are discussed for the management of minimally suspicious lesions and for screening mammography. PMID- 1930012 TI - Fine needle aspiration in the chest under CT control. AB - Over a 42 month period 133 patients underwent 148 CT guided biopsies of 104 pulmonary lesions (78%), 21 mediastinal/hilar masses (16%) and 8 pleural lesions (6%). There were 48 cases (32%) complicated by a pneumothorax, of which 13 (9%) required a chest drain. Two cases each of minor haemopneumothorax (1.4%) and haematoma (1.4%) were found, and haemoptysis occurred in a single patient (0.7%). This low complication rate reflects the use of the 22 gauge Chiba needle, the small number of passes undertaken at each sitting and the wide range of lesion size. In four cases no diagnosis was established either at the time of biopsy or subsequently. There were 100 cases proven to be malignant, of which 81 were diagnosed at the first biopsy. Three further cases were regarded as suspicious of malignancy. Of the 29 patients with benign disease, a specific diagnosis was made in 10 (34%) and nonspecific inflammation was seen in 17 (59%) further patients. Fine needle aspiration under CT control is a useful and accurate diagnostic technique. It has widened the scope of lesions which can be biopsied, enabling small, deep or necrotic parenchymal lesions to be targeted accurately. A precise placement of the needle tip into pleural or mediastinal lesions is a further advantage. However, if an inadequate sample is obtained, the biopsy may need to be repeated. PMID- 1930013 TI - Modified Gianturco arterial stents--preliminary results in iliac arteries of sheep. AB - Modified Gianturco arterial stents were placed in the iliac arteries of 3 non atherogenic sheep. At three months after placement there was no evidence of migration of the stents or of excessive intimal overgrowth in relation to the stents. PMID- 1930014 TI - Review of laser assisted angioplasty. PMID- 1930015 TI - Infra-hyoid metastases in supra-hyoid squamous cell carcinoma. AB - The CT scans of 71 patients with primary squamous cell tumours of head and neck sites were reviewed and compared with clinical examination in the assessment of lymph nodes above and below the hyoid. Above the hyoid, CT and clinical examination disagreed on the presence or absence of metastases in 13/42 cases (31%); below the hyoid where palpation is presumably easier, there was disagreement in 1 of 10 cases (10%). Abandoning infra-hyoid scans to save scanner time would save only seven slices on average per case and it is possible that further, clinically silent lesions would be missed. We conclude that staging scans in head and neck cancer should continue to include the infra-hyoid region. The inadequacies of existing knowledge based on clinical staging are discussed. PMID- 1930016 TI - Computed tomographic and ultrasound appearances of focal spared areas in fatty infiltration of the liver. AB - Computed tomography (CT) and ultrasound (US) appearances of diffuse and focal fatty infiltration of the liver (FIL) are well recognized. We have recently seen 10 cases with "fat spared" areas in FIL presenting as pseudo tumours of the liver. Characteristic appearances of fat free areas in FIL which help differentiate these areas from other focal liver lesions include (i) location in the medial segment of the left lobe of the liver, (ii) absence of mass effect on surrounding vessels and liver tissue, and (iii) presence of typical changes of FIL elsewhere in the liver on CT or US examination. PMID- 1930017 TI - Nodal recurrence in primary malignant epithelial tumours of the parotid gland. AB - An analysis has been made of the incidence of nodal recurrence in 237 patients with primary carcinoma of the parotid gland. Fifty eight patients (24.4%) developed nodal metastases; mostly in the cervical region. Eighteen of these metastases were within the radiation field and 13 were outside the radiation field. Factors which were predictive for nodal relapse were: Age greater than 60 years, T3 and T4 tumours, node metastases at initial presentation, and macroscopic disease at either the primary site or the nodal site. The complete response rate for treatment of nodal relapse was 19% and the partial response rate was 17.2%. The 5 year actuarial survival from the time of first presentation was 58%. The pattern of nodal recurrence in this study indicates that radiation portals should cover more than the first eschalon (upper deep cervical) nodes. Our current policy is to recommend elective irradiation of the lower cervical nodes in patients with primary parotid malignancies. PMID- 1930018 TI - Follicular thyroid carcinoma masquerading as subacute thyroiditis. Diagnosis using ultrasonography and radionuclide thyroid angiography. AB - The rare presentation of a follicular thyroid carcinoma mimicking the clinical and radionuclide features of subacute thyroiditis is described. Granulomatous thyroiditis was initially suspected on the clinical basis of acute onset of a hard, tender right lobe thyroid enlargement with associated systemic symptoms, modest elevation of thyroid hormone levels and suppressed thyroid RAIU. Fine needle aspiration cytology specimens were unsatisfactory for characterization. Three weeks later the thyroid RAIU was normal. The thyroid enlargement persisted, now being clearly visualized as a hypofunctional nodule on scintiscan. Repeat fine needle aspiration cytology was suggestive of acinar proliferation with hyperfunction. Ultrasonography revealed a solid nodule with a peripheral sonolucent halo. Radionuclide angiography showed intense arterial flow of Tc-99m pertechnetate through the right lobe thyroid enlargement suggestive of malignant thyroid pathology. Surgical excision and histopathological examination revealed a follicular carcinoma involving the right lobe. The possibility of carcinomatous involvement should be considered in those patients where initially tender thyroid nodularity persists longer than expected for a benign inflammatory disease, careful follow-up and relevant investigations being necessary to confirm the diagnosis. PMID- 1930019 TI - Cancer survival in Tasmania: a preliminary report. PMID- 1930020 TI - Brown-Sequard syndrome following chemotherapy and radiotherapy in breast carcinoma--a case report. PMID- 1930021 TI - Two patients with primary non-Hodgkin's lymphoma of the brain. PMID- 1930022 TI - Antenatal ultrasonic diagnosis of Meckel Gruber syndrome (a case report with review of literature). AB - Meckel Gruber syndrome is a rare autosomal recessive disorder with major characteristic features consisting of occipital encephalocele, polydactyly and polycystic kidneys along with other associated malformation. Antenatal ultrasonic examination can establish the correct diagnosis by identifying at least two of the major features described. The antenatal ultrasonic findings and pathology of this uncommon entity are discussed. PMID- 1930024 TI - Atypical case of Pott's disease. AB - An unusual case of Pott's Disease in an adult, Australian born, caucasian male is reported. The typical and atypical radiological features of spinal tuberculosis are reviewed. PMID- 1930023 TI - CT findings in lipoma of the flexor retinaculum of the palm. PMID- 1930025 TI - Patellar metastases in the presence of chondrocalcinosis. PMID- 1930026 TI - Transdiaphragmatic rupture of calcified hepatic hydatid cyst. PMID- 1930027 TI - Glide wire assisted removal of blocked pigtail nephrostomy catheters. PMID- 1930028 TI - Patterns of care studies in Australasia. PMID- 1930029 TI - The influence of paternal height and weight on birth-weight. AB - Analysis of 5,989 couples, for whom fathers' and mothers' heights and weights were recorded, showed that paternal height had a significant influence (p less than 0.0007) on birth-weight while paternal body mass index (Quetelets Index) had no significant effect (p greater than 0.05). Depending upon mother's height, the average effect of father's height (ranging from 165 cm to 184 cm) on birth-weight was up to 152 g, with a greater effect where the mother was taller (up to 235 g) and a lesser effect where the mother was shorter (confirming the effect of maternal constraint). The significance of these findings lies more with the need to consider this effect as an important variable in statistical analysis involving birth-weight than in its immediate obstetrical implications. PMID- 1930030 TI - Early onset neonatal group B streptococcus (GBS) infection: associated obstetric risk factors. AB - An analysis of all early onset neonatal Group B streptococcal (GBS) infections at the Royal Women's Hospital, Melbourne was made for the 10-year period 1979-1988. There were 104 cases with 29 neonatal deaths (28%). One or more predisposing perinatal risk factors was evident in 82% of cases (premature labour 79%, prolonged membrane rupture (greater than 12 hours) 57%, premature rupture of the membranes 69%, maternal sepsis 29%). Overall, 88% of GBS infections were evident within 24 hours of birth, suggesting an intrapartum pathogenesis for infection. PMID- 1930031 TI - Group B streptococcus (GBS) and neonatal infections: the case for intrapartum chemoprophylaxis. AB - At the Royal Women's Hospital, Melbourne over an 8-year period (1981-1988) all public antenatal patients were screened at 32 weeks' gestation for group B streptococcus (GBS). In a total of 30,197 livebirths there were no early onset neonatal GBS infections in infants of treated asymptomatic carrier mothers. By contrast there were 27 infections with 8 deaths in an unscreened control group of private patients (total livebirths 26,915). It is recommended that GBS screening occur antenatally at 28 weeks and that intrapartum chemoprophylaxis be offered at least to those carriers with obstetric risk factors. PMID- 1930032 TI - Management of infective endocarditis in pregnancy. PMID- 1930033 TI - A case controlled study of pregnancy complicated by severe maternal anaemia. AB - The perinatal outcome of 96 patients who had an antenatal haemoglobin value of less than 8.0 g/dl was compared with that of a similar number of controls who were matched for age and parity. Sixty-one patients (63%) had iron deficiency anaemia, 25 (26%) had alpha or beta thalassaemia minor, 7 (7.3%) had iron deficiency and thalassaemia trait, 2 had idiopathic pancytopenia and 1 had haemolytic anaemia due to systemic lupus erythematosus. Patients in the study group attended the antenatal booking clinic later, had less weight gain during pregnancy and their babies had lower birth-weights (2,984 g versus 3,177 g p less than 0.01) although there was no significant difference in the period of gestation at delivery. Six patients in the study group had placental abruption and another 2 patients had stillbirths but neither of these complications occurred in the control group. Although 37 patients (39%) in the study group received an antenatal blood transfusion, 53 (55%) of this group also had postnatal anaemia. PMID- 1930034 TI - Systemic lupus erythematosus and pregnancy at the Royal Women's Hospital, Brisbane 1979-1989. AB - The management and obstetric outcome of 17 patients with systemic lupus erythematosus (SLE) complicating 42 pregnancies is presented. Similar to world figures there was a 14.3% incidence of therapeutic abortion, a 4.8% incidence of ectopic pregnancy, a 16.7% incidence of spontaneous abortion, a 23.8% incidence of prematurity, a 4.8% incidence of fetal death in utero (FDIU) and a 9.5% incidence of intrauterine growth retardation (IUGR). In patients with antiphospholipid antibodies the obstetric outcome was significantly worse. Pregnancies complicated by preexisting renal compromise all concluded with an adverse outcome to the conceptus. In light of the experiences at the Royal Women's Hospital and a review of the world literature, the need for a standardized approach to SLE in pregnancy and more importantly the need for a large, prospective randomized trial of low dose aspirin in these pregnancies is highlighted. PMID- 1930035 TI - Oxytocin titration for induction of labour: a prospective randomized study of 15 versus 30 minute dose increment schedules. AB - Two hundred and twenty four patients admitted for induction of labour were randomized into 2 groups. The oxytocin dose was escalated every 15 minutes in the first group whilst for the second group the dose was increased every 30 minutes till optimal uterine activity was achieved. There was no significant difference in the mean maximum dose of oxytocin and length of labour in the 2 groups studied. Transient reduction of the dose of oxytocin was needed in 20.5% of patients in the '15 minute' group and 17.0% of cases in the '30 minute' group because of uterine hyperstimulation or fetal heart rate (FHR) changes; this difference was not statistically significant. The incidence of operative deliveries were similar in the 2 groups. The neonatal 1 and 5 minute Apgar scores, cord arterial blood pH, incidence of assisted ventilation and admission to the neonatal intensive care unit were similar in the 2 groups. The 15 minute schedule does not offer any advantage over the 30 minute escalation schedule for induction of labour. Hyperstimulation and FHR changes are a possibility with any regimen and close monitoring of FHR and uterine activity is advisable with the use of oxytocin. PMID- 1930036 TI - The clinical value of Clearplan home ovulation detection kits in infertility practice. AB - A home ovulation testing kit, Clearplan, that detects the urinary luteinizing hormone (LH) surge was used by 32 patients on a donor insemination programme for 50 cycles to indicate when to first attend the clinic for a serum LH test to determine ovulation. Using Clearplan significantly reduced the number of clinic attendances (4.06 +/- 1.5) compared to the preceding control cycle (7.06 +/- 2.0 p less than 0.001). One serum LH peak was missed using Clearplan. Ovulation was predicted within 2 days of the serum LH surge in 77% of cycles. Home ovulation determination has the potential to reduce the stress and cost of fertility programmes. PMID- 1930037 TI - Positive chlamydial serology and its effect on factors influencing outcome of IVF treatment. AB - A retrospective study of 98 IVF treatment cycles from 49 couples has assessed the relationship between presence of antibodies to Chlamydia trachomatis and success with respect to fertilization, cleavage and pregnancy rate, both at nidation and term. No effect of prior infection on IVF outcome was noted. PMID- 1930038 TI - Hysterectomy revisited. AB - This paper summarizes the results obtained in 279 vaginal hysterectomies performed in the 5 years 1985-1989 in the public and private practices of a single gynaecologist. It is suggested that it is feasible and safe to perform a hysterectomy vaginally in preference to the abdominal route in the majority of women, even in the absence of uterine descent. It is essential that registrars in training continue to be thoroughly versed in the techniques of vaginal surgery if such techniques are not to be forgotten. PMID- 1930039 TI - Prevalence and characteristics of women who have had a hysterectomy in a community survey. AB - A community survey of 8,896 households was undertaken in the Hunter region of New South Wales to assess women's health status. Consent was gained from 5,781 of the 6,361 eligible women between 18 and 69 years of age. The prevalence of hysterectomy in this sample was 16.9%, with 34.2% of women in their fifties having had a hysterectomy. Most hysterectomies (75%) were performed on women between the ages of 30 and 49 years. The demographic variables of parent's country of birth, educational level and employment status predicted recent hysterectomies after controlling for the effect of age. PMID- 1930040 TI - Repeat sterilization reversal. AB - Thirteen women had repeat sterilization reversal using microsurgery either because of failed IVF or personal preference for microsurgery. Six pregnancies occurred in 5 women resulting in 5 livebirths and 1 miscarriage. Pregnancy occurred in all 3 patients having isthmic anastomosis in the second sterilization reversal. Preliminary hysteroscopic tubal cannulation would have excluded operation on 2 patients who had tubal blockage extending several centimetres proximal to the site of the first anastomosis. PMID- 1930041 TI - Borderline epithelial ovarian tumours. AB - Twenty-four patients with borderline epithelial ovarian tumours treated in the Department of Obstetrics and Gynaecology of Hacettepe University during the last 12 years were evaluated with regard to histopathology, therapeutic modalities employed and outcome. No mortality was encountered among the 23 patients with Stage 1 disease, regardless of the surgical mode of treatment or adjuvant therapy. The related literature was reviewed briefly to help enlighten the controversial issue of borderline ovarian tumours. PMID- 1930042 TI - Pseudomyxoma peritonei--experience from a tertiary referral centre. AB - Pseudomyxoma peritonei is a clinical diagnosis of massive abdominal swelling by a gelatinous material, produced usually from an ovarian or appendiceal primary. It is a rare entity that is usually histologically benign but behaves clinically in a malignant fashion with recurrent growth, although not demonstrating histological stromal invasion. The disease remains localized to the peritoneal cavity and the clinical course is one of repeated episodes of intestinal obstruction caused by extrinsic compression that seem only to be relieved by surgical debulking. Variable responses have been obtained with adjuvant chemo-, radio- and immunotherapy, but these isolated responses are unable to be reproduced and so there is no accepted adjuvant treatment for this disease. PMID- 1930043 TI - An acardiac twin. PMID- 1930044 TI - Multifocal endometrial type carcinoma involving 5 primary sites in the pelvis. AB - A case of widespread endometrioid carcinoma is reported. The concept of multifocal carcinoma in the pelvis is discussed. PMID- 1930045 TI - Symphysiotomy for the trapped aftercoming part of the breech. PMID- 1930046 TI - Prostaglandin inhibitors during pregnancy and the effect on the fetus. PMID- 1930047 TI - Abnormal cervical cytology in Queensland. PMID- 1930048 TI - Conservative surgical management of ectopic pregnancy. PMID- 1930049 TI - Intrauterine surgery using electrocautery. PMID- 1930051 TI - Visual acuity of the U.S. Navy jet pilot and the use of the helmet sun visor. AB - Visor wear habits, evaluative comments and vision test data were obtained from interviews of 126 Navy fighter pilots. The interviews revealed that many pilots use their helmet sun visor whenever they fly, some use it only during certain flight operations, and others never use it. Study 1 (conducted at 343 cd/m2) revealed a decrease in low contrast visual acuity attributable to helmet sun visor use in the presence of a glare source. These findings prompted a second study of the visual effects of visor transmittance. Low-contrast spot detection, acuity, and contrast sensitivity were measured at an operationally realistic daytime illumination level (6870 cd/m2) in subjects viewing through filters ranging from 6.3% to 50.1% transmission. (Standard visor transmission is 12 +/- 4%.) Results showed that filter density, and consequently the illuminance reaching the eyes, could be varied over a wide range without critically affecting these visual functions. Prevailing environmental illuminance should be considered when selecting sun visors or sunglasses. These results have implications for optimizing visual performance through visors. PMID- 1930050 TI - Possible causes linking asphyxia, thick meconium and respiratory distress. AB - The cause of fetal distress and neonatal respiratory distress (RD) in association with meconium-stained liquor is not always clear. To clarify this, a prospective study was undertaken in a tertiary referral maternity hospital for 1 year. In all infants born after meconium-stained liquor who developed RD, evidence was sought for 1) fetal distress (from the cardiotocograph (CTG), the cord blood pH, the Apgar score and the asphyxial complications in the neonate) 2) causes of fetal distress (including maternal risk factors, fetal infection and fetal malnutrition) 3) causes of respiratory distress (including meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN) and infection). Of 4,026 livebirths, 717 (17.8%) had meconium-stained liquor and 44 term and 5 preterm infants developed RD. In the 44 term infants, there was frequent evidence of fetal distress possibly caused by previously unrecognized factors such as fetal malnutrition with reduced neonatal skinfold thickness in 35% triceps and 41% subscapular measurements, and histological chorioamnionitis (CA) in 74%. The cause for respiratory distress was identified in only 48% of infants, and included clinical evidence of PPHN (41%), MAS (16%) and infection (2%). However in preterm infants, 80% had definite or suspected infection. The findings indicate that fetal distress is common in infants who develop respiratory distress after meconium-stained liquor. A role for histological CA and reduced nutrition in the fetus, as factors contributing to the vulnerability of the term infant to intrapartum fetal distress, is suggested. PMID- 1930052 TI - Stereotypes of pilots and apprehension about flying with them: a study of commercial aviation scenarios. AB - This study explored the effects of gender, experience, and performance of a commercial aviation pilot on concern of passengers about flying with him or her. It used scenarios that represented two aspects of pilot behavior: skill and judgment. We cast 112 adult subjects in the role of passengers. They read vignettes that described their captain and the flight in a 2 x 2 x 2 factorial design (male or female, newly promoted or veteran captain, strong or weak performance). Results showed that of the three manipulated variables, only pilot performance had a statistically significant main effect upon apprehension about making a continuation flight with the pilot (F = 41.52; p less than or equal to 0.001 for the skill scenario and F = 41.73; p less than or equal to 0.001 for the judgment scenario). Statistical interactions showed that the level of passenger concern was not based entirely on pilot performance. For instance, on the skill scenario, when a female pilot performed well, her rating was higher than that of an equally performing male, but when she performed poorly, her rating was lower than his (F = 5.38; p less than or equal to 0.02). PMID- 1930053 TI - Effects of dexamethasone and high terrestrial altitude on cognitive performance and affect. AB - This study examined the effects of dexamethasone and exposure to high terrestrial altitude on cognitive performance, affect, and personality. Cognitive performance was evaluated by five cognitive tasks, affect was evaluated by the Clyde Mood Scale and the Multiple Affect Adjective Check List, and personality was examined using the Minnesota Multiphasic Personality Inventory. Sixteen healthy young men received either dexamethasone (4 mg every 6 h) (n = 7) or placebo (n = 9) for 34 h prior to and 52 h after ascent to 4,300 m. Subjects treated with dexamethasone correctly performed more computer interaction and addition problems than did placebo-treated subjects. They also were less sleepy, dizzy, depressed, and anxious than placebo-treated subjects at altitude. No adverse effects on cognitive performance, affect, or personality were noted after dexamethasone was discontinued on the third day at altitude. Results indicate that dexamethasone at the present dose positively influences cognitive performance and mood states at altitude, but has no residual effect on personality. PMID- 1930054 TI - Peripheral cold acclimatization in Antarctic scuba divers. AB - Peripheral acclimatization to cold in scuba divers stationed at the British Antarctic Survey's Signy Station was investigated during a year in Antarctica. Five divers and five non-diver controls underwent monthly laboratory tests of index finger immersion in cold water for 30 min. Index finger pulp temperature and time of onset of cold-induced vasodilatation (CIVD) were measured. Pain was recorded with verbal and numerical psychophysical subjective pain ratings. Average finger temperatures and median finger pain from 6-30 min of immersion, maximum finger temperatures during the first CIVD cycle, and finger temperatures at the onset of CIVD were calculated. Comparison of the variables recorded from divers and non-divers were performed with analysis of variance. No significant differences were found among the variables recorded from divers and non-divers. From a review of the literature, divers have responses typical of non-cold adapted Caucasians. There is, therefore, no evidence that Signy divers peripherally acclimatized to cold. We suggest that these findings occur because either the whole body cooling which divers undergo inhibits peripheral acclimatization or because of insufficiently frequent or severe cold exposure while diving. Further basic studies on the duration, frequency and severity of cold exposure necessary to induce peripheral cold acclimatization are required before this question can be satisfactorily answered. PMID- 1930055 TI - Immersed clo insulation in marine work suits using human and thermal manikin data. AB - The immersed clo value of a series of 11 marine work suits has been measured using both humans and a thermal manikin. In still water, there is no significant difference in the measurements. Turbulent water significantly reduces the immersed clo value. The manikin errs on the safe side and consistently overestimates this decrement in insulation, and the reasons for this are discussed. Not intended to replace human physiological testing, the manikin is an excellent apparatus for the examination of conditions not easily or ethically possible to represent using humans. A good fitting suit with efficient neck, wrist and ankle closures which reduce flushing of water is essential to make an effective marine work suit. PMID- 1930056 TI - Biodynamic simulations of the effect of a neck-mounted air bag on the head/neck response during high G acceleration. AB - New helmet-mounted devices (such as night-vision goggles, laser eye protection, etc.) have created new safety hazards for pilots during ejection or high G maneuvering. In order to prevent the resulting head/neck injuries, this study extends the air-bag protection system developed for ground vehicles to a neck mounted system for aircrew personnel. Results, carried out by computer biodynamic simulations using the Articulated Total Body Model (ATB), showed that: 1) helmet weight had little effect on head/neck torque, contact force and flexion angle; 2) initial head/neck position and center of gravity offsets of the helmet-mounted devices had significant effects on head-neck torques, contact forces, and neck flexion angles; and 3) the neck mounted air bag significantly reduced neck torques, contact forces, and neck flexion angles. We conclude that the neck mounted air bag system could significantly reduce the severity of head/neck injuries to pilots during ejection or high G maneuvering. PMID- 1930057 TI - Alterations in human upper extremity motor function during acute exposure to simulated altitude. AB - We tested the hypothesis that mild motor dysfunction was associated with Acute Mountain Sickness (AMS) by measuring arm movement characteristics in 14 subjects at sea level and at the end of a 30-h simulated altitude exposure (4,600 m). A computerized upper extremity movement analyzer (UEMA) was used to quantitate arm movements between a "start" position and randomly-generated targets on a large digitizing tablet by measuring selected speed parameters and error indices. The UEMA results were compared with the results of the Environmental Symptoms Questionnaire (ESQ) and with neurologic examinations. When compared with sea level values, the mean values for all the speed-related parameters measured at the end of the 30-h exposure significantly declined by 20% to 32%. The error indices were not different. The declines in the speed-related parameters were significantly correlated with the severity of AMS symptoms as measured by the ESQ (R = 0.82). The neurologic abnormalities were limited to changes in mental status items. These results demonstrate that subclinical alterations in upper extremity speed are associated with mild, reversible AMS and provide evidence that hypoxia may produce supraspinal inhibition of motor pathways. PMID- 1930058 TI - Altered sensorimotor control of the body as an etiological factor in space motion sickness. AB - Exposure to nonterrestrial force levels affects the activity of gravitoinertial force sensitive receptors of the body, both of labyrinthine and nonlabyrinthine origin. It also disrupts the normal patterning of motor control of body orientation and movement. The patterns and levels of muscle innervation necessary to achieve particular body configurations and to bring about particular body movements are greatly affected by background force level and body orientation relative to the force vector. The present studies demonstrate that such altered sensorimotor control of head and body posture along with altered vestibulomotor control are evocative of motion sickness. This observation has explanatory significance both for space motion sickness and the re-entry disturbances that occur after prolonged spaceflight. PMID- 1930059 TI - Preparing for war: lessons learned from U.S. Army flight nurses of World War II. AB - The combat posture of today's military forces, and more specifically the emphasis on medical readiness for members of the health care professions, shows that the involvement of flight nurses in armed conflict cannot be ruled out. As part of a larger study of how military nurses cope with war, 25 former U.S. Army flight nurses of World War II were interviewed to learn how they coped with wartime situations they perceived as taxing or exceeding their resources. The purpose of this paper is to describe those aspects of wartime nursing that flight nurses interviewed would like to have been different and, subsequently, what advice they would offer today's flight nurses. The responses are examined within the theoretical framework of stress, appraisal, and coping developed by Lazarus and colleagues. PMID- 1930060 TI - A double-blind placebo controlled evaluation of acupressure in the treatment of motion sickness. AB - We used 36 subjects in a double-blind placebo controlled experiment to evaluate the effectiveness of acupressure as a prophylaxis against motion sickness. There were two independent variables with two levels each: acupressure vs. placebo, and motion sickness high vs. low susceptible subjects. The provocative stimulus was rotation about two orthogonal axes. Signs and symptoms of motion sickness were scored both by the subject and the observer. In spite of previous reports to the contrary, acupressure provided no protection against motion sickness for either high or low susceptible subjects. PMID- 1930061 TI - Rapid onset of severe heat illness: a case report. AB - Aviators flying extended periods in hot environments are known to be at risk for heat-related illness. The risk when wearing chemical individual protective equipment (IPE) is increased even at relatively warm temperatures and light workloads. In this paper, we report the physiological responses of an aviator who had been flying a UH-1H helicopter up to 6 h/d clothed in full IPE on 6 consecutive days prior to the sudden onset of heat illness. His performance during the study was normal, and no clear physiological derangements were noted prior to his symptoms. The rapid evolution of his symptoms after voicing no complaints provides a graphic illustration of the difficult predictability and initial central nervous system effects of this condition. PMID- 1930062 TI - Testing the tests--an empirical evaluation of screening tests for the detection of cognitive impairment in aviators. AB - The FAA has expressed concern that flight safety could be compromised by undetected cognitive impairment in pilots due to conditions such as substance abuse, mental illness, and neuropsychological problems. Interest has been shown in the possibility of adding a brief "mini-mental exam," or a simple automated test-battery to the standard flight medical to screen for such conditions. The research reported here involved the empirical evaluation of two "mini-mental exams," two paper-and-pencil test batteries, and a prototype version of an automated screening battery. Sensitivity, specificity, and positive predictive value were calculated for each sub-task in a discriminant study of 54 pilots and 62 individuals from a heterogeneous clinical population. Results suggest that the "mini-mental exams" are poor candidates for a screening test. The automated battery showed the best discrimination performance, in part because of the incorporation of dual-task tests of divided attention performance. These tests appear to be particularly sensitive to otherwise difficult-to-detect cognitive impairments of a mild or subtle nature. The use of an automated battery of tests as a screening instrument does appear to be feasible in principle, but the practical success of a screening program is heavily dependent upon the actual prevalence of cognitive impairment in the medical applicant population. PMID- 1930063 TI - Mortality and cancer morbidity after exposure to military aircraft fuel. AB - In order to elucidate a possible excess risk of lymphatic malignancies due to aircraft fuel exposure in the Swedish Armed Forces (SAF), a historical prospective cohort study was conducted. During a 9-year follow-up period, 3 cases of malignant lymphoma were detected versus 3.21 expected tumors of the lymphatic system (standardized incidence ratio (SIR) 93; 95% confidence interval (CI) 19 273) among 2,176 men. The overall SIR was 91 (CI 66-120), whereas the corresponding mortality ratio was only 54 (CI 42-68; p less than 0.001). In conclusion, no evidence was found for an association between military aircraft fuel and the occurrence of malignant lymphomas or other malignancies among exposed men in the SAF. For a definite risk assessment, further follow-up is necessary. PMID- 1930064 TI - Use of sentinel health events (occupational) in computer assisted occupational health surveillance. AB - The U.S. Coast Guard has developed a Coast Guard-wide comprehensive system for surveillance of workplace diseases. The American Medical Association's fifth edition of the Current Medical Information and Terminology (CMIT) was used as a reference to expand the basic list of 50 Sentinel Health Events (Occupational) [SHE(O)] published by the National Institute of Occupational Health and Safety (NIOSH), September, 1983. The expanded list of 107 sentinel events serves as a framework for the development of a computerized system of occupational health surveillance in the U.S. Coast Guard. This application of SHE(O) surveillance can have application in the early detection and prevention of environmental diseases. PMID- 1930065 TI - The Golden Fleece Award for cabin safety research. PMID- 1930066 TI - The psycho-motor performance as a part of the selection of applicants for training in the Belgian Air Force. PMID- 1930067 TI - The history of the United States Air Force physician program. PMID- 1930068 TI - Prescriptive eyeglass use by U.S. Navy jet pilots: effects on air-to-air target detection. AB - Air-to-air target detection distances, age, career jet flight hours, and total career flight hours were obtained for 167 U.S. Navy fighter pilots participating in air combat maneuver training at Naval Air Station, Oceana, VA. Of the pilots sampled, 22 used a prescribed spectacle correction while flying; 145 did not. We compared the air-to-air target detection distances between the two groups of pilots, those with corrective glasses and those without. Sunglasses and tinted filters were not factors in the present study. The results strongly suggest that, as a group, the pilots without glasses were able to detect targets at a greater distance than the pilots with glasses. When the pilots were matched on the basis of age and flight experience, the difference in air-to-air target detection capabilities of the two groups increased. The pilots without glasses were able to detect their adversary at a distance more than 20% farther than the pilots with glasses. PMID- 1930069 TI - Work-related aviation fatalities in Colorado 1982-1987. AB - On-the-job deaths related to aviation are the seventh leading cause of fatal occupational injury in the United States. In Colorado, they comprise 37% of all air transport deaths. A review of all occupational aviation-related fatalities in Colorado during 1982-1987 identified 86 deaths. Data sources were death certificates, Workers' Compensation records, and National Transportation Safety Board reports. Of the fatalities, 5 involved commercial air service, 16 were military personnel, and 65 (76%) were associated with general aviation. Non military occupations included 21 pilots, 5 flight instructors, 4 crop sprayers, and 3 search and rescue workers or firefighters. There were 18 people going to or from work sites. The 15 weather cases, 7 aircraft malfunctions, and 4 power transmission wire strikes were the most significant factors in two-thirds of the crashes of civilian aircraft. Even experienced pilots exercised poor judgement. The prominence of general aviation in work-related aviation fatalities indicates a need for greater attention to the safety of workers whose jobs entail flying. PMID- 1930070 TI - The measurement of psychophysiological reactions of pilots to a stressor in a flight simulator. AB - Seventeen Boeing 737 pilots were exposed to an acute stressor in a flight simulator: a birdstrike between V1 (velocity of aircraft on take-off run at which crew is committed to take-off regardless of any incidents occurring) and VR (velocity of aircraft at take-off). Certain physiological variables together with state anxiety scores were measured at different stages of the simulated flight. Levels of plasma cortisol, norepinephrine, total protein, total lipid, lactate, and the haematocrit changed significantly across the test conditions. Plasma epinephrine, osmolality and glucose levels did not change significantly across the test conditions. Captains and copilots differed significantly in the profiles obtained for the state anxiety scores. The variables measured in this study demonstrated different profiles in response to the stressor. Conceptual and methodological problems need to be solved before an integrated psychophysiological approach to the reactions of pilots to stressors can be developed. PMID- 1930071 TI - Dietary intake and blood lipid profile survey of fighter pilots at Tyndall Air Force Base. AB - A 24-hour dietary recall, a food frequency checklist, and a blood lipid profile were collected from 30 USAF fighter pilots. Sample mean intakes of nutrients studied met U.S. military recommended dietary allowances, except for folic acid, which was 78%. Mean percentages of energy derived from carbohydrate, protein and fat were 48.3, 16.1 and 34.2%, respectively. Of the pilot sample, 63% reported they did not eat breakfast daily. Sample mean blood lipid profile values were: total cholesterol = 218 mg/dl, HDL-cholesterol = 45 mg/dl, triglycerides = 109 mg/dl. Based on total cholesterol level, 40% of the pilot sample should have follow-up according to the National Cholesterol Education Program. A significant negative relationship was found between reported exercise frequency and total cholesterol/HDL-cholesterol ratio. Some fighter pilots could benefit from counseling with a dietitian regarding dietary intake patterns, decreasing dietary fats, and the advantages of regular exercise. PMID- 1930072 TI - Contribution of core cooling rate to shivering thermogenesis during cold water immersion. AB - The contribution of core cooling rate to the thermogenic response in humans, for a similar combination of core and peripheral thermal inputs, was studied. Seven male subjects were immersed in 15 degrees C water on two occasions. Trial A was conducted without any intervention. During Trial B extremity blood flow was occluded for 10 min to allow limb blood to cool toward the temperature of the surrounding tissues. Upon release of cuff pressure the cooled, trapped blood returned to the core region instigating a decrease in esophageal temperature (Tes), with a concomitant increase in heat production (H). The slope of the Tes-H relationship during the dynamic post-occlusion phase was defined as central thermosensitivity (beta B). The slope of the Tes-H relationship during Trial A (beta A), evaluated over a similar range of core temperatures but over a longer time period, was compared with beta B to determine the influence of core cooling rate on the thermogenic response. The rate of core cooling (Tes) increased from 0.05 +/- 0.01 degrees C.min-1 in Trial A to -0.23 +/- 0.02 degrees C.min-1 with cuff occlusion-release in Trial B, resulting in a significant increase in beta B when compared to beta A (-2.99 +/- 0.36 vs. -1.90 +/- 0.24 W.kg-1.degrees C-1). Results of this study indicate that during cold water immersion: 1) dynamic core temperature significantly contributes to the magnitude of metabolic heat production; and 2) individual differences exist in central thermosensitivity. PMID- 1930073 TI - Facial cooling does not benefit cardiac dynamics during recovery from exercise hyperthermia. AB - Cardiovascular responses during passive recovery following exercise-induced hyperthermia were investigated in male subjects (n = 8) on two separate occasions; once with facial cooling (FC; 2 degrees C, 2.5 m/s) and once without (NC). Recovery heart rate (HR) responses were significantly (p less than 0.05) lower during the FC than NC condition. No statistical differences were observed between groups with respect to stroke volume (SV), cardiac output (CO), systemic vascular resistance (SVR), and mean arterial blood pressure (MAP). After 5 min of recovery, FC caused a significant (p less than 0.05) reduction in HR however, the NC group response remained unchanged. The decline in HR with FC was moderately associated with the decrease in forehead temperature (r = 0.69; p less than 0.05) but poorly correlated with rectal temperature (r = 0.09; p greater than 0.05). As expected, SV, CO, and MAP significantly declined (p less than 0.05) while the estimated SVR progressively increased (p less than 0.05) over time. The results suggest that FC is not beneficial in terms of improving central and peripheral cardiovascular dynamics during recovery from exercise-induced hyperthermia. PMID- 1930074 TI - Gender-based differences in the cardiovascular response to standing. AB - Reduced tolerance to orthostatic stress is a recognized consequence of spaceflight. Both men and women serve as astronauts and are staying longer in space. While there are recognized cardiovascular differences in baseline function based on gender, little is known about any gender-based differences in cardiovascular responses to orthostatic stress. The purpose of this study was to compare the cardiovascular responses of men and women to the stand test. The subjects were 10 men and 10 women, 20-30 years of age. Heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were monitored during 5 min supine and 5 min standing. Men responded similarly in heart rate (39 vs. 35%); but had significantly greater decreases in stroke volume (-53 vs. -40%), cardiac output (-36 vs. -21%), and pulse pressure (-19 vs. -12%); and greater increases in blood pressure (11 vs. 6%) and total peripheral resistance (77 vs. 34%) than did the women. Men and women demonstrated fundamental differences in cardiovascular responses during standing. Differences in the height of the subjects did not account for these differing cardiovascular responses. The mechanisms for these differences are not yet clear. Men and women should be studied as separate groups until these differences are understood. PMID- 1930075 TI - Effect of caffeine ingestion on alveolar ventilation during moderate exercise. AB - The purpose of this study was to examine the effect of caffeine ingestion on alveolar ventilation and physiological dead space ventilation during exercise in high and low caffeine users. Eleven males (mean age 26.4 +/- 5.4 years), classified as either high caffeine users (greater than 350 mg/d, n = 6) or low caffeine users (less than 50 mg/d, n = 5) performed two treadmill exercise conditions at a constant work rate (50% VO2max) 45 min after ingestion of 3.3 mg of caffeine/kg body weight or placebo using a double-blind protocol. Open circuit spirometry was used to determine ventilatory and gas exchange variables every 10 min during the 50 min of walking exercise. Analysis of variance showed that caffeine produced significant differences in alveolar ventilation (VA) and the physiological dead space ventilation/tidal volume ratio (VD/VT) with VA increased from 1.36 to 1.54 L/breath and VD/VT decreased from 22.3 to 20.5% between the placebo and caffeine treatments, respectively. Additionally, caffeine ingestion produced a significant increase in tidal volume (VT) and a significant decrease in frequency of breathing (fb). We conclude that caffeine consumed prior to exercise enhances ventilatory dynamics during exercise without regard to prior habitual caffeine consumption. PMID- 1930076 TI - Relationships between symptoms, moods, performance, and acute mountain sickness at 4,700 meters. AB - Ascents above 4,000 m adversely affect symptoms, moods, and performance and cause acute mountain sickness (AMS). It is assumed that individuals afflicted with AMS will be more susceptible to changes in these other parameters; however, previous studies have suggested that their time courses are different. This investigation analyzed the relationships between symptoms, moods, and performance and a measure of altitude sickness, the AMS-cerebral (AMS-C) factor of the environmental Symptoms Questionnaire (ESQ). We evaluated 20 male soldiers on 11 symptom, 13 mood, and 14 cognitive/motor performance measures after exposure to altitudes of 550 and 4,700 m for 5-7 h and a difference score was calculated for each measure. The difference scores for 70% of the symptom, 46.2% of the mood, and 28.6% of the performance measures were significantly correlated with the AMS-C difference score. The difference scores for each measure were then rank ordered (to standardize for differences across measures) and the sum of the ranks was calculated for each subject's symptoms, moods, and performance. The AMS-C factor score correlated significantly 0.90, 0.77, and 0.59 with these composite measures of symptoms, moods, and performance, respectively. Changes in AMS after 5-7 at 4,700 m were correlated best with changes in symptoms, then moods, and finally performance, suggesting that these parameters may be differentially affected at this point in time. PMID- 1930078 TI - The effect of a space food bar diet on body and muscle mass in normal and hind limb suspended rats. AB - A food bar diet is used for rats in space flight. Since ground based studies have only been performed with the typical rat chow in dry pellet form, we tested whether the food bar diet allows normal growth and normal response of muscle protein content to unloading. These parameters were measured in normal and tail cast hind limb suspended rats fed standard pellets or food bars. Body mass following 5 d of hind limb unloading was similar in bar-fed (97.9 +/- 4.8 g) and pellet-fed (92.6 +/- 3.4 g) animals (p greater than 0.05). In addition, gains in body mass were comparable between bar-fed (5.3 g/d) and pellet-fed (5.1 g/d) animals. Food bar consumption over 6 d increased from 10.5 to 12.0 g/d animal. During 5 d of hind limb suspension, food bar consumption increased from 13.2 +/- 1.4 to 19.1 +/- 1.4 g/d per animal. In agreement with previous studies, hind limb unloading reduced soleus muscle mass and protein content per 100 g body mass in both diet groups (p less than 0.05). Protein content per 100 g body mass was unchanged for the plantaris, extensor digitorum longus and tibialis anterior muscles during suspension in both diet groups. Rodent consumption of a food bar diet results in normal gains in body mass and muscle protein when compared to a standard pellet diet, and does not alter the atrophic response of skeletal muscle to unloading. PMID- 1930077 TI - The effects of hypobaric hypoxia on specific B cell responses following immunization in mice and humans. AB - In order to get some insight on the physiology of the immune system during prolonged exposure to hypobaric hypoxia we evaluated the effects of high altitude on the in vivo immune response to a T-independent antigen. A group of 18 men who participated in a scientific project EV-K2-CNR to Mount Poumori, Nepal for 20 d at 4,930 m (16,174 ft) were immunized with a single subcutaneous dose of antimeningococcal vaccine Menpovax A + C (Sclavo) containing 50 micrograms of polysaccharide A (PsA) and 50 micrograms of polysaccharide C (PsC) of N. meningitidis. A group of 18 men of comparable age were vaccinated at sea level. Antibody titers against both polysaccharides were determined by enzyme-linked immunosorbent assay (ELISA) before and 18 d after vaccination. All subjects examined developed a good antibody response and no statistically significant differences were observed between the two groups. Spectrotypic analysis of antibody response to PsC was also performed by isoelectric focusing. No qualitative differences in the antibody response to PsC were found in the hypoxia exposed group with respect to the control group. A group of 10 BALB/c inbred mice were kept in a hypobaric chamber at 5,500 m (18,000 ft) for 30 d. After 10 d, the mice were vaccinated with 1 micrograms of Menpovax A + C. Anti-PsA and anti-PsC antibodies were quantified by ELISA in sera collected at day 0 and 30. A control group of 10 mice of the same strain underwent the same study protocol but at sea level. Both groups developed a good antibody response to both polysaccharides and no significant differences were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930079 TI - White finger symptoms: a cross-sectional study. AB - In a cross-sectional questionnaire study of 2,933 employees of a Swedish aircraft company, the prevalence of white finger (wf) was asked for and then correlated with information on personal and anthropometrical data and on job-related and leisure related activities. The questionnaire return rate was 96%. There were 210 (7%) who reported white finger symptoms. A positive association with age and with work with vibrating hand-tools (polishing and deburring instruments and marking pens) and a negative association with body weight was found. The higher proportion of wf among female workers did not retain statistical significance after consideration of their lesser weight in the multivariate testing. The highest proportion of wf was found among polishers/grinders (23%), sheet-metal workers (19%) and cleaners (15%). We conclude that work with vibrating hand-tools of the type used in this industry probably increases the prevalence of wf and that ways to better insulate tools need to be evaluated. PMID- 1930080 TI - Medical causes of in-flight incapacitation: USAF experience 1978-1987. AB - In-flight incapacitation of a fully trained crewmember due to a serious underlying medical condition is a rather infrequent event. In order to delineate the extent and nature of the incapacitation problem we reviewed the data base at the Air Force Safety and Inspection Center for all incidents coded for incapacitation, preexisting disease, or other acute illnesses occurring during the 10 years between 1978 and 1987. During this period there were 23 in-flight incidents of incapacitation due to significant underlying medical conditions. In 11 of the incidents the incapacitation resulted in a loss of consciousness. Neurologic conditions were the most frequent cause followed by cardiovascular conditions. We calculated a rate of incapacitation as 0.19 per million aircrew flying hours. PMID- 1930081 TI - Disposable soft lens ulcerative keratitis in an Army aviator: a case report. AB - A synopsis of Army aviation interest in soft contact lenses is presented. A case report of one volunteer subject's experience with presumed contact lens associated infectious ulcerative keratitis then is summarized. The clinical significance of this case is highlighted. PMID- 1930082 TI - Factors associated with leukocyturia in asymptomatic pilots. AB - We attempted to relate the prevalence of leukocyturia during annual examinations to recent activities and history data in 923 pilots. Urinary analysis was done and the results cross-tabulated with answers from a questionnaire and with a past history of leukocyturia obtained from the pilot's chart. The prevalence of 4 to 6 or more white blood cells (WBCs) in the urinary sediment was 5.3%. Leukocyturia was 35.7 times more common (odds ratio) in those with a previous history of leukocyturia and a concomitant history of urethritis (p less than 0.0001). Yet, a history of leukocyturia accounted for only 18.1% of the cases of leukocyturia. There was a trend for an association between jogging and leukocyturia. The prevalence of leukocyturia was not affected by smoking, other physical exercise, a history of nephrolithiasis, air duty in the preceding 24 h or a history of transient illness during the last 2 weeks. We conclude that there is an association between a history of both leukocyturia and urethritis and leukocyturia. In most cases, however none of the variables tested were found to be associated with leukocyturia. PMID- 1930083 TI - Speech analysis as an index of alcohol intoxication--the Exxon Valdez accident. AB - As part of its investigation of the EXXON VALDEZ tankship accident and oil spill, the National Transportation Safety Board (NTSB) examined the master's speech for alcohol-related effects. Recorded speech samples were obtained from marine radio communications tapes. The samples were tested for four effects associated with alcohol consumption is available scientific literature: slowed speech, speech errors, misarticulation of difficult sounds ("slurring"), and audible changes in speech quality. It was found that speech immediately before and after the accident displayed large changes of the sort associated with alcohol consumption. These changes were not readily explained by fatigue, psychological stress, drug effects, or medical problems. Speech analysis appears to be a useful technique to provide secondary evidence of alcohol impairment. PMID- 1930084 TI - A comparison between computer-controlled and set work rate exercise based on target heart rate. AB - Good exercise prescriptions provide work rates (WRs) that maintain heart rates (HR) in a target zone and at a percent of maximum metabolic equivalent (%METmax). HR and MET were evaluated from computer-controlled and set WR (constant speed) sessions (20 min at 65% METmax). Computer-controlled WR used a control algorithm to adjust speed and grade to maintain the target HR. The set WR (mean +/- S.D.) HR (139 +/- 8 bpm) was lower (p less than 0.05) than the target (147 +/- 3 bpm) and computer-controlled HRs (153 +/- 5 bpm). The set WR MET (8.6 +/- 2.2) was not different than the target (8.6 +/- 2.2), but both were lower than computer controlled exercise (9.7 +/- 2.2). Computer-control time in target HR zone (16 +/ 5 min) was significantly (p less than 0.004) greater than set WR exercise (6 +/- 5 min). Computer-controlled WR was significantly better in maintaining target HR and the MET values were not physiologically different than target WRs. PMID- 1930085 TI - Current research and trends in aviation psychology in Poland. AB - Basic trends of research carried out in Poland during the past decade within the Military Institute of Aviation Medicine were reviewed. Aviation psychological research has concentrated around four important problems: 1) personality determinants of the occupational functioning of pilots including (a) temperamental factors and the occupational adaptation of pilots, (b) personality determinants (i.e., manifested attitudes towards vocation) of the occupational adjustment of pilots, (c) personality correlates of the psychosomatic costs of pilots' vocational adjustments; 2) perceptual efficiency mechanisms of task performance in flight simulators--the research objective was to study visualmotor mechanisms associated with compensatory perception in the process of training for aviation tasks requiring visual-motor coordination; eye movements were measured as an index of perception of visual information. 3) psychological criteria in predicting success in pilot training--the external criterion was the assessment of progress in practical flight training; and 4) computer assisted psychological research. PMID- 1930086 TI - Flying after dining guidelines: A review. PMID- 1930087 TI - Aeromedical evacuation of patients with Lassa fever. PMID- 1930088 TI - You're the flight surgeon: Recurrent atrial fibrillation with no evidence of precipitating disease. PMID- 1930089 TI - The influenza virus-infected host cell, a target for the immune response. AB - The exposure of some viral antigens at the surface of infected host cells was studied as an essential stimulus for the immune response during influenza virus infections. Only antibodies directed against the HA1 of the haemagglutinin were bound to the cell surface, anti-HA2 antibodies did not gain access to the membrane. Attempts to purify the cell-associated haemagglutinin (formerly called "viromicrosomes" by, R. Rott) indicated the formation of a special form of truncated haemagglutinin. This antigen and the nucleoprotein was purified from infected chorioallantoic membranes by immunoaffinity chromatography. NP-specific epitopes could not be defined on the native NP molecule which seems to be in solution in a discoordinate and partially polymeric array. Three non-overlapping epitopes were assigned to proteolytic peptides of the NP. Purified NP could induce cross-reactive cytotoxic T-cells in mice, but these animals were not protected against a challenge infection. CTL induced by exogenous stimulation or intracellular synthesis of the NP were restricted by MHC class I in both cases. NP could be incorporated into ISCOM after amphiphatic modification of the molecule. NP-ISCOM conferred some protection to experimental mice, but did not induce CTL demonstrable in vitro. PMID- 1930090 TI - Mechanisms of pathogenicity in infectious diseases. PMID- 1930091 TI - Modification of the cleavage activation of the influenza virus hemagglutinin by site-specific mutagenesis. AB - Factors determining cleavability of influenza virus hemagglutinin which is activated by ubiquitous cellular endoproteases were analysed by carrying out site directed mutagenesis on the cloned hemaglutinin genes of strains A/FPV/Rostock/34 (subtype H7) and A/Port Chalmers/1/73 (subtype H3). Substitutions at the cleavage site of the H7 hemagglutinin indicate that the tetrapeptide Arg-X-Lys/Arg-Arg is the minimal consensus sequence recognized by the ubiquitous proteases. The H3 hemagglutinin also became susceptible to these enzymes, when additional arginines were inserted at the cleavage site. Three arginines were sufficient, when the carbohydrate was removed, whereas four additional arginines are needed when this carbohydrate was present, indicating that the accessibility of the cleavage motif is important for the protease. The appropriate localization of the basic cleavage motif within the amino acid sequence and the spatial structure of the hemagglutinin precursor is an additional prerequisite for cleavage. PMID- 1930092 TI - Some aspects of animal papovaviruses. PMID- 1930093 TI - Virus-induced amyloidoses. AB - After a short introduction into the general concept of amyloidoses and the genetic disposition involved in these diseases, the genetic disposition for unconventional virus diseases (or transmissible spongiform encephalopathies) and the disease specific amyloid are described. Experimental studies on the pathogenesis and the infectious agent suggest that scrapie and related diseases are virus-induced amyloidoses of the brain. PMID- 1930094 TI - Clostridial neurotoxins: from toxins to therapeutic tools? AB - Tetanus toxin and botulinum toxins are powerful neurotoxins which block neurotransmitter release through an unknown mechanism my means of their light chains. The heavy chains provide the machinery for neuroselective binding, internalization, retrograde intraaxonal transport, and translocation of the L chains into the cytosole. We have cloned and sequenced the structural genes of tetanus toxin and of five serologically distinct botulinum toxins to identify structurally and functionally conserved subdomains. The minimum essential domains of the L-chains of tetanus and botulinum toxin type A were identified by combined in vitro transcription and microinjection of L-chain specific mRNA into identified presynaptic neurons of Aplysia californica. In addition, a nontoxic mutant of tetanus was generated by replacing histidine(237) by a proline residue. The development of nontoxic neuroselective transporter molecules carrying various marker enzymes is discussed. PMID- 1930095 TI - Molecular and immunopathological studies of borna disease virus infection in rats. AB - Borna disease virus is an agent distinct from all known viruses. Pathogenesis of its infection is also unique. This review highlights several aspects of the biology of this viral infection and the preliminary characterization of the agent. BDV can be used to answer important questions in neurobiology. These include neuroinvasiveness and neurotropism of viral agents, CD4+ T cell-mediated immunopathology and tolerance in newborn animals to a persistent viral infection in the CNS and behavioral diseases and eating disorders induced by neurotropic viruses. This review is dedicated to Prof. Dr. Rott on occasion of his 65th birthday in recognition of his immense contributions to studies on Borna disease and also for his success focusing the attention of the scientific community to this still evolving unique viral disease. PMID- 1930096 TI - 9-O-acetylated sialic acid, a receptor determinant for influenza C virus and coronaviruses. AB - Influenza C virus and a group of coronaviruses, a typical representative of which is bovine coronavirus, use the same strategy for binding to cells. Surface components containing 9-O-acetylated sialic acid are recognized as cellular receptors by these viruses. In addition to the receptor determinant both virus groups have a receptor-destroying enzyme in common, which has been identified as a sialate 9-O-acetylesterase. Differences are, however, found in the distribution of these activities on the viral surface proteins. The influenza C glycoprotein HEF is a multifunctional protein, which is responsible for receptor-binding, receptor-inactivation and fusion. In the case of coronaviruses these activities are functions of two different glycoproteins, S and HE. PMID- 1930097 TI - On the enzymes which make "fatty proteins". AB - Twelve years have passed since the initial report on the modification of viral proteins with covalently linked fatty acids appeared (Schmidt et al., 1979). With gratitude the first author and his students look back on a number of fruitful and happy years in Professor Rott's department, during which we contributed to furthering insight into the fatty acylation of proteins. Following the initial discovery this area has expanded tremendously, and as reflected by a great number of review articles (e.g. Schmidt 1982a; Low 1987, Schulz et al., 1988; Towler et al., 1988; Grand 1989; Schmidt 1989; Schmidt and Schlesinger, 1991) research on "hydrophobic modifications of proteins" has occupied virologists, cell-biologists and biochemists alike. Rather than duplicating the circulating reviews at this stage we take this occasion to report new data on the enzymatic nature of fatty acylation. We believe that the knowledge of the acylating enzymes will provide the cornerstone for full understanding of this hydrophobic modification of proteins. PMID- 1930098 TI - Demonstration of virus-specific cytotoxic T lymphocytes in liver tissue in hepatitis A--a model for immunopathological reactions. AB - The pathogenetic mechanism leading to liver tissue injury in hepatitis caused by hepatitis A virus is unclear. We have randomly established T cell clones from liver biopsies from 4 patients with hepatitis A. A total of 578 clones was phenotypically analyzed. Whereas during the acute phase of disease CD8+ clones dominated over CD4+ clones, from a biopsy taken late after onset of clinical syndromes more CD4+ than CD8+ clones were obtained. Interestingly, in a patient with a second exacerbation of the disease, more than 20% of all clones had the CD3+ WT31- CD4- CD8- gamma delta TCR+ phenotype. Variable IFN-gamma production was observed with all types of T cell clones. All CD8+ clones had cytotoxic activity, and approximately 60% of all CD8+ clones showed specific cytotoxicity against autologous fibroblasts infected with hepatitis A virus but not with herpes simplex, adeno- or enteroviruses. These results show that the liver injury in hepatitis A is not caused by a viral cytopathogenic effect but is due to an immunopathological reaction of sensitized cytotoxic T lymphocytes against infected hepatocytes. In addition, these studies show an enrichment of CD4-8- alpha beta T cell receptor negative T lymphocytes at the site of an inflammation and suggest a role of these cells in an antiviral reaction. PMID- 1930100 TI - Persistent virus infections in studies of the immune response. AB - Some recent studies on immune phenomena in persistent virus infections, employing non-cytolytic viruses, are reviewed. This includes the refutation of a possible inheritance of tolerance and some aspects of drug-induced tolerance to persistent viruses, with its consequences for possible treatment of virus-induced immunopathological diseases. The biological peculiarities of viruses involved in persistent or chronic infections are discussed with respect to the balance between the immune system and the infectious agent. PMID- 1930101 TI - Processing of influenza virus hemagglutinin in insect cells. PMID- 1930099 TI - On the penetration mechanism of influenza viruses. AB - The envelopes of influenza viruses contain in addition to lipids also two glycoproteins, the hemagglutinin and the neuraminidase, that are responsible for the adsorption, receptor splitting, penetration and budding processes of these viruses. In this article, hypotheses presented in the past with regard to the virus penetration are reconsidered. Based on results obtained with the fowl plague virus (influenza A/FPV/Rostock/34, H7N1) and MDCK-cells, we conclude that a fusion between the viral envelope and the plasma membrane is the initial step of virus entry. PMID- 1930102 TI - Paramyxovirus tropism dependent on host proteases activating the viral fusion glycoprotein. AB - An essential step in paramyxovirus fusion (F) glycoprotein biosynthesis is the posttranslational endoproteolytic cleavage of the inactive precursor glycoprotein Fo by host cell proteases. When the Fo possesses a pair or a cluster of basic residues at the cleavage site, cleavage is catalyzed by a ubiquitous protease(s) and the infection is consequently pantropic. When the site is monobasic with a single arginine, cleavage is allowed to occur only by the enzyme(s) expressed in limited tissue types and the infection is localized there. We have isolated from chick embryo an example of the latter type of endoprotease specific for the single arginine motif and demonstrate its identity with the clotting factor Xa. The ectopic expression of the FXa appeared to be the sole determinant for the viral tropism in chick embryo. The latter type of protease specific for a paired or multiple basic cleavage motif have neither been identified nor characterized extensively. We show here that this cleavage can be induced by the yeast KEX2 protease, a unique subtilisin-like serine protease, responsible for pro factor processing at the paired basic sites. PMID- 1930103 TI - Synthesis and function of influenza A virus glycoproteins. AB - The surface glycoproteins of influenza A viruses are the viral components first recognized by the immune system of the infected host, and they are the viral proteins first to contact the infecting cell. Cleavage of the hemagglutinin (HA) is the presupposition for the uptake and fusion between viral and endosomal membranes at a relatively low pH. If this cleavage does not occur during synthesis and migration within the cell, an external trypsin-like protease has to activate the virus with a non-cleaved HA. This latter property is presumably the reason, why such a large reservoir of non-pathogenic influenza A viruses could be built up in water fowl. Especially feral ducks can disseminate influenza viruses along their flight routes all over the world. The role of the neuraminidase (NA) in the infectious process is not so clear. Its main task in the natural infection seems to be removal of mucoids at the site of entry and in this way to start the primary infection. The synthesis of the viral proteins is a highly regulated process. There is not only a transcriptional but also a translational control. The viral glycoproteins belong to the late proteins. Specifically their synthesis can be inhibited by compounds acting in completely different ways like a specific methylase inhibitor (3DA-Ado), a protein phosphokinase C inhibitor (H7), or a lipid solvent (DMSO). It remains to be determined whether the underlining mechanism is in all these cases the same, namely posttranscriptional modification of viral mRNA. All these viral components do not act separately but they cooperate in their functions and sometimes interfere with each other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930104 TI - Plaque formation of Newcastle disease virus in primary chicken kidney cells. AB - Using primary chicken kidney (PCK) cells, a plaque assay was carried out with an avirulent strain of Newcastle disease virus (NDV) without adding trypsin to the agar overlay medium. The plaque assay was done in less than 4 days in PCK cells, by 3 days earlier than in primary chicken embryo (CE) cells maintained in the presence of trypsin. The curves of the progeny virus production began to rise 6 h after the infection and reached a plateau at 12 h. Equal amounts of virus were produced in PCK cells both in the presence and absence of trypsin in the culture medium. Viral peptide analysis revealed that a large portion of the HN and F precursor envelope glycoproteins of the NDV-Ulster strain remained uncleaved in PCK-grown virions. This suggests that a marginal proteolytic cleavage of these glycoprotein suffices for the full growth of the progeny virus in PCK cells. A higher shut-off in the host protein synthesis occurred in the virus-infected PCK cells than in the infected CE cells. PMID- 1930105 TI - Biochemical and genetical analysis of AZT-resistant HIV-mutants. AB - Sequential virus isolates from an HIV-1-infected woman treated orally with 3' azido-3'-deoxythymidine (AZT) for over two years showed a 10-fold reduced sensitivity for AZT after 8 months and a 100-fold resistance after 24-32 months of drug therapy. These AZT-resistant mutants were totally sensitive in vitro to other reverse transcriptase (RT)-inhibitors like the AZT-analogue 3'-fluoro-3' deoxythymidine (FdT) or the chemically less related nucleoside analogue 2',3' dideoxycytosine (ddC). Even the benzodiazepin derivative 4,5,6,7-tetrahydro-5 methyl-6-(3-methyl-2-butenyl)-imidazo [4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (TIBO), a new drug specific for HIV-1 RT, was inhibitory for these virus strains. Moreover, compounds with different modes of action, e.g. polysulfated polyxylan, exhibited full antiviral activity as well. Thus, AZT resistance seems to be highly specific and should allow to develop further drugs to be used when AZT resistance has emerged. 5.9 kb fragments of the 5'-genomic halves of these sequential HIV-isolates were amplified by PCR and cloned. DNA sequence analysis revealed that the RT gene of the two highly AZT-resistant isolates carried two of the mutations described by Larder et al. [Science 246, (1989)], the Lys 70----Arg and the Thr 215----Tyr transitions. The isolate obtained after 32 months of AZT therapy in addition contained a third mutation at position 67 (Asp----Asn); in contrast to Larder's report, no mutation was found at position 219. Thus, although these virus isolates showed at least a 100-fold reduced susceptibility for AZT in vitro, the four mutations postulated to be relevant for highly resistant strains were only partially confirmed. PMID- 1930106 TI - Tyrosine kinases: from viral oncogenes to developmental regulators. AB - Protein tyrosine kinases (PTKs) play a central role in cellular regulation by virtue of their participation in, and control of, signal transduction pathways; they act as a molecular interface between the cell's environment and intercellular metabolism. The mammary gland, unlike most organs, undergoes most of its morphogenesis in juvenile and adult life. The epithelium goes through hormonally controlled cycles of proliferation and regression, the fully differentiated state only being reached at the end of pregnancy. These features make the mammary gland an amenable tissue to study the involvement of PTKs in epithelial cell development and differentiation. We have used a PCR-based molecular cloning strategy to identify PTKs from murine mammary gland cells. Amongst 70 kinase clones characterized we found 3 PTKs previously undescribed in mouse, 4 known PTKs and 5 serine threonine kinases. Expression studies revealed differential tissue specificity and developmental regulation of the 3 previously undescribed PTKs. These results substantiate the view that PTKs are involved in the regulation of cellular differentiation. PMID- 1930107 TI - Prevalence of blood protozoan parasites of avian species in Nsukka area of Anambra State, Nigeria. AB - A total of 165 avian species (110 chickens, 15 turkeys, 12 ducks, 10 each of geese and guinea fowls, and 8 pigeons) were examined for blood protozoan parasites. Blood samples were collected from the wing veins and smears with Giemsa stain. Plasmodium spp. were found in 2 chickens (1.6%) and 7 turkeys (46.6%). 5 turkeys were clinical cases. 3 (37.5%) of the pigeons were positive for Haemoproteus spp. No blood parasites were found in geese, ducks, and guinea fowls. The results show that avian malaria can constitute a health problem in poultry, especially turkeys, in Nigeria. The avian species may act as a reservoir host for human malaria parasites. PMID- 1930108 TI - Helminth parasitism of domestic fowl (Gallus domesticus L.) in a subtropical high rainfall area of India. AB - An investigation into the helminth parasitic infections of domestic fowl in a subtropical area of India, based on an autopsy of 532 chickens, revealed a 90.9% prevalence of infection. 10 species of helminths were encountered, of which Capillaria contorta was recorded for the first time from fowls in India. Ascaridia galli was the most prevalent species, followed by Raillietina spp. and Heterakis gallinae. The infection by trematodes appeared to be very rare. The helminth fauna of fowls in this climatic area was compared with that of fowls in other areas of the world and found to differ in respect of prevalence and incidence of various parasitic species. The role of the climate in the distribution and in regulating populations of parasitic species is discussed. PMID- 1930110 TI - [The occurrence of tumors in large bears (Ursidae)--a literature review and six case descriptions]. AB - Histological findings on two Malayan sun bears and four sloth bears show that malignant neoplasms play an important role in tropic bears. Further, most of the tumors originated from the hepatic and biliary tract. Our results were compared with other investigations on zoo animals during the last 70 years revealing that malignant neoplasms are the most common ones in bears of the family Ursidae. Accordingly to our results, sloth and Malayan sun bears seem to have a disposition to develop malignant neoplasms of the hepatic and biliary tract, but within other species only polar bears seem to suffer predominantly from such neoplasia. The reason for this phenomenon could be an alimentary intake of carcinogens. Furthermore, Malayan sun bears show very often neoplasms of the thyroid gland as it is also observed in other carnivora. PMID- 1930109 TI - [The virulence of L. leucocephala for goats in northeastern Mexico]. AB - When fed 100% Leucaena during a period of 45 days goats with experience in L. fodder took significantly (P less than 0.05) more dry matter (50.01 g/kg0.75) than those without or only possible experience (44.40 g/kg0.75 and 45.63 g/kg0.75). The uptake of Mimosine from animals with Mimosine experience (1.14 g/kg0.75) has also been significantly higher (P less than 0.05) than from two other groups with non or only possible experience (0.93 g/kg0.75 and 0.92 g/kg0.75). The Serum-Thyroxin level (T4) of the control group (5.12 micrograms/100 ml) and of the group with Leucaena experience (4.65 micrograms/100 ml) has been significantly higher (P less than 0.05) during the entire trial period than that of the two other trial groups (3.9 micrograms/100 ml). Hair loss, reduced fodder uptake, increased salivation, excitation, ataxia of hind legs, vomit of fodder and uncoordinated chewing of fodder have been observed in animals without or only possible Leucaena experience. Three animals of those died through direct or indirect influence of the poisoning. Swollen buccal papillae, ulceration and necrosis of the oesophagus and haemorrhagic lesions in the reticulum and rumen have been observed in two of the dead animals. PMID- 1930111 TI - [Clinical case report: unilateral malformation of the eye of a thoroughbred foal]. AB - A unilateral malformation of the eye of a thoroughbred foal is described. The specific form of the tiny lens we named, "lenticulus". It is correlated with a maximal unchangeable mydriasis. The bulb shows physiological size. A brown-black pigmented mass inhibited (internal) inspection and examination of the middle and rear part of the eye. Special emphasis is laid on the insecure behaviour of the foal. A connection with an iridocyclochoroiditis, which was treated in the mare about a year ago, and the pathological changes in the eye of the foal is not evident. PMID- 1930112 TI - [Detection of antibodies against Chlamydia in swine by an immunofluorescent test and an enzyme immunoassay]. AB - Chlamydial IgG-antibodies were detected in 130 of 2050 porcine sera (6.3%) using an indirect immunofluorescence assay (IFA). Antibody titers varied between 1:8 and 1:16 in 87 sera (67%) and reached titers from 1:32 to 1:128 in 43 sera (33%). An ELISA closely related to the IFA-technique was developed, which confirmed the IFA-positive and IFA-negative results in 93% and 86% respectively. A significant higher percentage of positive IFA-titers greater than or equal to 1:32 was obtained from sows with abortions and infertility as well as from store pigs with pneumonia than from healthy pigs (p less than 0.5). PMID- 1930113 TI - [The fat content in the muscles of three selected lines of German Landrace swine. Effects of graded feeding intensity on muscle fattening. Muscle fat content in relation to parameters of body fat deposits]. AB - Investigations on muscle fat content and intramuscular adipose tissue pattern of 51 male castrated pigs were performed. For each body 4 muscles were collected after slaughter. Breeding lines of swine (German Landrace) had been selected through 8 generations for high ("E(+)-Line") and low ("E(-)-Line") levels of NADPH-generating dehydrogenases including a control group without selection. 42 animals were kept under feeding experiments of various energy levels from 60 kg up to 100 kg body mass. Additionally, out of control line 5 piglets (25 kg) and 4 hogs (135 kg) were examined. Data of ether-extracted total fat content versus data of fat marbling planimetry correlated well with r = 0.9. The average degrees of muscle fattening were: m. semispinalis capitis (11%) much much greater than m. psoas major (1.8%) greater than m. semimembranosus (1.7%) greater than m. long thoracis (1.3%). The specific internal relation of muscle fattening with respect to the collected samples was calculated as r = 0.8. Intramuscular fat showed the tendency to increase with higher levels of dietary energy. The E(+)-Line showed higher (16%) muscle fattening than the E(-)-Line. The control group, however, showed 44% higher levels than the E(+)-Line. So, the results of that K degree Line could not serve as baseline for interpretations. The criteria of thickness and harmony of marbling scores were used to make statements of meat quality: The samples of m. psoas major and E(+)-Line reached the best, the samples of m. semispinalis capitis and the K degree-Line reached the least values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930114 TI - Biotechnology between science push and consumer pull. PMID- 1930115 TI - Epidemiology of food allergy and food intolerance. PMID- 1930116 TI - Nutritional and dietetic aspects of food allergy and food intolerance in childhood. PMID- 1930117 TI - Reduction of milk protein allergenicity through processing. PMID- 1930118 TI - Practical aspects of food allergy and food intolerance. A consumer's perspective. PMID- 1930119 TI - Food allergy and food intolerance: lessons from the past and hopes for the 21st century. PMID- 1930120 TI - Food intolerance and allergy--definitions and spectrum of clinical features. PMID- 1930121 TI - Mechanisms of food allergy and food intolerance. PMID- 1930122 TI - Mucosal immunology and food antigens. PMID- 1930123 TI - Cow's milk protein allergy. PMID- 1930124 TI - Biogenic amines. PMID- 1930125 TI - The role of food additives and intolerance reactions to food. PMID- 1930126 TI - Hyperactivity and food additives. PMID- 1930127 TI - The evolution in research in prolamin toxicity: from bread to peptide. PMID- 1930129 TI - Interaction of beta-lactamases I and II from Bacillus cereus with semisynthetic cephamycins. Kinetic studies. AB - The influence of C-6 alpha- or C-7 alpha-methoxylation of the beta-lactam ring in the catalytic action of class A and B beta-lactamases has been investigated. For this purpose the kinetic behaviour of beta-lactamases I (class A) and II (class B) from Bacillus cereus was analysed by using several cephamycins, moxalactam, temocillin and related antibiotics. These compounds behaved as poor substrates for beta-lactamase II, with high Km values and very low catalytic efficiencies. In the case of beta-lactamase I, the substitution of a methoxy group for a H atom at C-7 alpha or C-6 alpha decreased the affinity of the substrates for the enzyme. Furthermore, the acylation of cephamycins was completely blocked, whereas that of penicillins was slowed down by a factor of 10(4)-10(5), acylation being the rate-determining step of the process. PMID- 1930130 TI - Surfactant protein D (SP-D) counteracts the inhibitory effect of surfactant protein A (SP-A) on phospholipid secretion by alveolar type II cells. Interaction of native SP-D with SP-A. AB - The surfactant proteins SP-A and SP-D were obtained from rats given intratracheal instillation of silica. SP-D was isolated from the 33,000 g supernatant of rat bronchoalveolar lavage fluids, and we examined whether SP-D affects surfactant secretion by alveolar type II cells. Native SP-D affected neither basal secretion nor stimulated secretion by type II cells. However, native SP-D counteracted the inhibitory effect of SP-A on surfactant secretion in a concentration-dependent manner; however, SP-D failed to counteract the inhibitory effect of concanavalin A. The activity of SP-D was unaffected by inclusion of excess methyl alpha mannoside. Excess native SP-D competed with 125I-SP-A for high-affinity binding to type II cells. Heat treatment of SP-D and antibody against SP-D both decreased SP-D activity. Butanol extraction of native SP-D was most effective at destroying SP-D activity and attenuated the ability of the protein to compete with labelled SP-A for binding to type II cells. The butanol-soluble fraction of SP-D possessed the ability to alter the inhibitory effect of SP-A to the same extent as native SP-D. Direct binding of 125I-SP-A on nitrocellulose sheets demonstrated that SP-A could bind native SP-D, but not butanol-extracted SP-D. We conclude that native SP-D alters SP-A activity in type II cells through interaction with it via SP-D associated lipids. PMID- 1930131 TI - Correlation between anthracycline structure and human DNA ligase inhibition. AB - A total of 19 anthracycline derivatives were tested for their ability to interfere in vitro with the action of the human replicative DNA ligase. Only those with the sugar devoid of unmodified amino groups or with large configurational modifications were found to be inactive. Maximal inhibition of DNA-joining activity was found to require a 4'-deoxy-3'-amino sugar. Self adenylation of DNA ligase was largely insensitive to these drugs. An important general finding is that slight modifications of the anthracycline structure have pronounced effects on DNA-ligase-inhibitory activity and might be related to the specificity of anthracycline anti-tumour activity. PMID- 1930132 TI - Estimation of peroxisomal and mitochondrial fatty acid oxidation in rat hepatocytes using tritiated substrates. AB - The pathways of peroxisomal and mitochondrial fatty acid oxidation were monitored with the use of substrates which produce NAD3H. I used as marker substrates: D-[3 3H]3-hydroxybutyrate for mitochondrial NAD3H production, [2-3H]glycerol for cytosolic NAD3H production, and [2-3H]acetate to measure carbon-bound 3H which was also generated by the metabolism of the commercial 9,10-3H-labelled fatty acids. The assumption that peroxisomal NAD3H can be considered to be equivalent to cytosolic NAD3H was supported using a specific inhibitor of mitochondrial fatty acid oxidation. The approach involves determination of the specific yields, and the relative distribution on carbons 4 and 6, of 3H in glucose from the marker substrates and the labelled fatty acids. In hepatocytes from clofibrate treated rats, the amount of palmitate or oleate oxidation which starts in the peroxisomes is comparable with that which starts in the mitochondria. PMID- 1930128 TI - The molecular anatomy of caldesmon. PMID- 1930133 TI - Purification and partial characterization of glutamate synthase from Rhodospirillum rubrum grown under nitrogen-fixing conditions. AB - Glutamate synthase, a key enzyme in ammonia assimilation, has been purified from the photosynthetic bacterium Rhodospirillum rubrum. The purification procedure involves ion-exchange chromatography, affinity chromatography and gel filtration. The recovery in the procedure is high (62%) and the specific activity is 21 mumol of NADPH oxidized/min per mg. The enzyme is specific for its substrates, and no activity was demonstrated with NADH or NH4+ ions substituting for NADPH and glutamine respectively. The enzyme is composed of two dissimilar subunits with molecular masses of 53 and 152 kDa, and it is shown that Cl- ions have an effect on the aggregation of the enzyme. Km values for the substrates are: NADPH, 16 microM; 2-oxoglutarate, 10 microM; and glutamine, 65 microM. The enzyme is inhibited by amidotransferase inhibitors at micromolar concentrations. The role of the enzyme in the metabolic regulation of nitrogenase is discussed. PMID- 1930134 TI - Purification and partial characterization of a pyruvate oxidoreductase from the photosynthetic bacterium Rhodospirillum rubrum grown under nitrogen-fixing conditions. AB - A pyruvate oxidoreductase with the capacity to support pyruvate-dependent nitrogenase activity in vitro has been purified from the photosynthetic bacterium Rhodospirillum rubrum. The enzyme requires CoA for activity and is irreversibly inactivated by oxygen. The molecular properties and Km values for the substrates have been studied. In supporting nitrogenase activity addition of ferredoxin is required. Overall the enzyme is similar to the nif-specific pyruvate: flavodoxin oxidoreductase purified from Klebsiella pneumoniae. PMID- 1930135 TI - Effects of brefeldin A on oligosaccharide processing. Evidence for decreased branching of complex-type glycans and increased formation of hybrid-type glycans. AB - Brefeldin A (BFA), a drug that induces redistribution of Golgi-apparatus proteins into the endoplasmic reticulum, was used to determine the role of subcellular compartmentalization in the processing of asparagine-linked oligosaccharides. Baby-hamster kidney cells were pulse-labelled with [3H]mannose for 30-60 min and chased for up to several hours in the presence or in the absence of BFA or labelled continuously for several hours with and without the drug. Cellular glycoproteins were digested to glycopeptides with Pronase and either fractionated into glycan classes by lectin affinity chromatography or digested further by endoglycosidase H and endoglycosidase D. Released oligosaccharides obtained in the latter procedure were then separated from each other and from endoglycosidase resistant glycopeptides by paper chromatography. The results show that BFA induces a very fast processing of protein-linked Glc3Man9GlcNAc2 oligosaccharide down to man5GlcNAc2 and conversion into complex-type and hybrid-type glycans. The major difference between untreated and BFA-treated cells is a large increase in bi-antennary and hybrid-type glycans in the latter cells. These results indicate that galactosylation of a mono-antennary GlcNAcMan5GlcNAc2 hybrid blocks subsequent action by mannosidase II and N-acetylglucosaminyl transferase II, producing galactosylated hybrid-type glycans. Similarly, galactosylation of the product of N-acetylglucosaminyltransferases I and II, i.e. a Man3GlcNAc2 core substituted with GlcNAc beta 1----2 on both alpha 1----3- and alpha 1----6-linked mannose residues, blocks branching N-acetylglucosaminyltransferases IV and V, thereby causing an increase in bi-antennary glycans and a decrease in tri- and tetra-antennary glycans. PMID- 1930136 TI - Collagenolytic cysteine proteinases of bone tissue. Cathepsin B, (pro)cathepsin L and a cathepsin L-like 70 kDa proteinase. AB - The aim of the work was to identify and characterize the cysteine proteinases of bone tissue, as these enzymes appear necessary for bone resorption. Three cysteine-dependent proteolytic activities were separated from a homogenate of mouse calvaria by a fractionation procedure involving (NH4)2SO4 precipitation, gel filtration and ion-exchange chromatography. The first two are typical cathepsins B and L with respect to (1) their reactivity with anti-(cathepsin B) and anti-(cathepsin L) antibodies respectively, (2) their relative rate constants for inhibition by benzyloxycarbonyl-Phe-Phe-CHN2 and L-3-carboxy-trans-2,3 epoxypropionyl-L-leucylamido-(4-guanid ino)butane and (3) their enzymic properties, such as the higher activities of cathepsin L against collagen and gelatin as compared with cathepsin B, and the fact that benzyloxycarbonyl-Arg-Arg 4-methoxy-2-naphthylamide is hydrolysed only by cathepsin B. Cathepsin L was mainly recovered in its precursor form, as indicated by its apparent 40 kDa molecular mass and its relative stability at pH 7.2. The third enzyme is a cathepsin L-like proteinase with an apparent molecular mass of 70 kDa. It is immunoprecipitated by anti-(cathepsin L) antibodies, and appears as the 25 kDa band of mature cathepsin L in Western blots. It further resembles (pro)cathepsin L with regard to its activities against synthetic substrates and proteins such as collagen, and with regard to its response to various inhibitors. However, unlike (pro)cathepsin L, it is eluted as a 70 kDa protein on gel filtration (even in the presence of 1% Brij or 1 M-NaCl), it is stable at pH values as high as 9, and it exhibits stronger affinity for phenyl-Sepharose. It might thus result from a strong complex between mature cathepsin L and another entity that confers stability at alkaline pH and favours hydrophobic interactions. This 70 kDa activity was also detected in mouse muscle and long bones of Ca(2+)-deficient chicks but not in mouse liver, spleen or kidney. PMID- 1930138 TI - Purification to homogeneity of Charonia lampas alpha-fucosidase by using sequential ligand-affinity chromatography. AB - An alpha-fucosidase from the liver of the marine gastropod Charonia lampas was purified to homogeneity using a procedure that included cation-exchange and gel filtration chromatography, chromatofocusing and a final series of affinity chromatography steps which involved the following gel-immobilized ligands: N-(5 carboxy-1-pentyl)-1,5-dideoxy-1,5-imino-L-fucitol, N-(5-carboxy-1-pentyl)-2 acetamido-1,5-imino-1,2,5-trideoxy-D-glucitol and thio-beta-D-galactoside. The enzyme was found to be a tetrameric glycoprotein with a native Mr of 208,000, and to exist in a number of isoforms displaying pI values in the range 6.0-6.4. Substrate-specificity studies using a number of fucosylated oligosaccharides of the lacto-N and lacto-N-neo series and a synthetic disaccharide confirmed that the enzyme catalyses the hydrolysis of a broad range of fucosidic linkages, and established the following hierarchy of susceptibility: Fuc alpha 2Gal beta 4Glc much much greater than Fuc alpha 6GlcNAc greater than Fuc alpha 2Gal beta 4GlcNAc greater than Gal beta 3(Fuc alpha 4)GlcNAC much much greater than Gal beta 4(Fuc alpha 3)GlcNAc. Similar relative rates of hydrolysis were also demonstrated using biantennary oligosaccharide alditols as substrates which contained fucose linked either alpha 3 or alpha 6 to the N-acetylglucosaminitol residue of the chitobiosyl core. PMID- 1930139 TI - Mechanism of acyl transfer by the class A serine beta-lactamase of Streptomyces albus G. AB - Optimization by energy minimization of stable complexes occurring along the pathway of hydrolysis of benzylpenicillin and cephalosporin C by the Streptomyces albus G beta-lactamase has highlighted a proton shuttle that may explain the catalytic mechanism of the beta-lactamases of class A. Five residues, S70, S130, N132, T235 and A237, are involved in ligand binding. The gamma-OH group of T235 and, in the case of benzylpenicillin, the gamma-OH group of S130 interact with the carboxylate group, on one side of the ligand molecule. The side-chain NH2 group of N132 and the carbonyl backbone of A237 interact with the exocyclic CONH amide bond, on the other side of the ligand. The backbone NH groups of S70 and A237 polarize the carbonyl group of the scissile beta-lactam amide bond. Four residues, S70, K73, S130 and E166, and two water molecules, W1 and W2, perform hydrolysis of the bound beta-lactam compound. E166, via W1, abstracts the proton from the gamma-OH group of S70. While losing its proton, the O-gamma atom of S70 attacks the carbonyl carbon atom of the beta-lactam ring and, concomitantly, the proton is delivered back to the adjacent nitrogen atom via W2, K73 and S130, thus achieving formation of the acyl-enzyme. Subsequently, E166 abstracts a proton from W1. While losing its proton, W1 attacks the carbonyl carbon atom of the S70 ester-linked acyl-enzyme and, concomitantly, re-entry of a water molecule W'1 replacing W1 allows E166 to deliver the proton back to the same carbonyl carbon atom, thus achieving hydrolysis of the beta-lactam compound and enzyme recovery. The model well explains the differences found in the kcat. values for hydrolysis of benzylpenicillin and cephalosporin C by the Streptomyces albus G beta lactamase. It also explains the effects caused by site-directed mutagenesis of the Bacillus cereus beta-lactamase I [Gibson, Christensen & Waley (1990) Biochem J. 272, 613-619]. PMID- 1930137 TI - Evidence for sterol-independent regulation of low-density lipoprotein receptor activity in Hep-G2 cells. AB - The relationship between the serum factor(s)-mediated induction of low-density lipoprotein (LDL) receptor activity and changes in cellular cholesterol metabolism was examined in the human hepatoma cell line Hep-G2. Relative to incubation with serum-free media [Eagle's minimal essential medium (MEM) control], short-term (less than 8 h) incubation with medium containing 15% of either calf serum (MEM + serum) or the d greater than 1.25 fraction of calf serum (MEM + d greater than 1.25) produced a time- and concentration-dependent increase in the uptake of 125I-LDL. Immunoblotting with anti-(LDL receptor) antibodies demonstrated that this was correlated with a 2-fold increase in the amount of the mature 136,000 Da LDL receptor protein in detergent-solubilized Hep-G2 cell membranes. Incubation with MEM + serum, but not MEM + d greater than 1.25, increased the efflux of radiolabelled cholesterol from Hep-G2 cells. However, the induction of 125I-LDL uptake by MEM + d greater than 1.25 (2.3-fold) and MEM + serum (2.2-fold) was virtually identical. Addition of the d less than 1.063 lipoproteins of calf serum to MEM + d greater than 1.25 at their original or three times their serum concentration decreased the induction of 125I-LDL uptake by MEM + d greater than 1.25 by only 20-30%. Together, these results suggest that the stimulation of 125I-LDL uptake was not due to the presence of high-density lipoprotein, the absence of LDL or the stimulation of cholesterol efflux. MEM + serum stimulated 125I-LDL uptake in cells cholesterol-loaded by incubation with rat very-low-density lipoprotein with beta electrophoretic mobility (beta-VLDL). Compared to incubation with the MEM control, either MEM + serum or MEM + d greater than 1.25 produced time-dependent increases in the activity of 3-hydroxy 3-methylglutaryl-CoA reductase which also occurred in cholesterol-loaded cells. However, cholesterol biosynthesis, whether measured from 3H2O, [14C]acetate or [3H]mevalonic acid, was not increased. Incubation with MEM + serum or MEM + d greater than 1.25 did not affect [3H]oleate incorporation into cellular cholesteryl esters, hydrolysis of intracellular [3H]cholesteryl esters or the cellular mass of unesterified or esterified cholesterol. Incubation with MEM + serum or MEM + d greater than 1.25 produced a transient increase in the level of LDL receptor mRNA, reaching a maximum of 5-10-fold by 2 h and decreasing to near baseline levels by 4 h. Actinomycin D blocked the serum-factor-mediated induction of LDL receptor mRNA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1930141 TI - L-phenylalanine ammonia-lyase from French bean (Phaseolus vulgaris L.). Characterization and differential expression of antigenic multiple Mr forms. AB - L-Phenylalanine ammonia-lyase (PAL; EC 4.3.1.5) purified from suspension-cultured cells of French bean (Phaseolus vulgaris) has been further characterized. A number of techniques, including use of an antiserum and affinity probes, have established that all the antigenic polypeptides represent polymorphic Mr forms of the enzyme. These peptides include an apparently higher-Mr (83,000) form which shows different kinetics of induction from the Mr-77000 forms that have been extensively characterized previously. The larger subunit appeared to be PAL by the following criteria: (a) binding to specific affinity and antibody matrices; (b) peptide mapping; (c) active-site labelling; and (d) amino acid composition. The increased Mr of the larger subunit was not completely attributable to glycosylation, although some sugar residues were detected in this Mr-83000 form but not in the other Mr forms. Mr-83000 subunits were also immunoprecipitated from translations in vitro of mRNA from cells that had been stressed for a long period. They were also detected in leaf tissues that were not yet undergoing an extensive wound response. This form of the enzyme may be constitutive and involved in the low-level accumulation of phenolics in most cell types. By contrast, the Mr-77000 forms of PAL were rapidly induced during elicitor action, wounding or cytokinin-induced xylogenesis as a key regulatory enzyme involved in the synthesis of phenolics under stress conditions or during differentiation. PMID- 1930140 TI - Amino acid sequence of the penicillin-binding protein/DD-peptidase of Streptomyces K15. Predicted secondary structures of the low Mr penicillin-binding proteins of class A. AB - The low-Mr penicillin-binding protein (PBP)/DD-transpeptidase of Streptomyces K15 is synthesized in the form of a 291-amino acid-residue precursor possessing a cleavable 29-amino acid-residue signal peptide. Sequence-similarity searches and hydrophobic-cluster analysis show that the Streptomyces K15 enzyme, the Escherichia coli PBPs/DD-carboxy-peptidases 5 and 6, the Bacillus subtilis PBP/DD carboxypeptidase 5 and the spoIIA product (a putative PBP involved in the sporulation of B. subtilis) are structurally related and form a distinct class A of low-Mr PBPs/DD-peptidases. The distribution of the hydrophobic clusters along the amino acid sequences also shows that the Streptomyces K15 PBP, and by extension the other PBPs of class A, have similarity in the polypeptide folding, with the beta-lactamases of class A, with as reference the Streptomyces albus G and Staphylococcus aureus beta-lactamases of known three-dimensional structure. This comparison allows one to predict most of the secondary structures in the PBPs and the amino acid motifs that define the enzyme active sites. PMID- 1930142 TI - Spectroscopic and binding studies on the stereoselective interaction of tyrosine with horseradish peroxidase and lactoperoxidase. AB - The interaction of a series of derivatives of tyrosine with horseradish peroxidase (HRP) and lactoperoxidase (LPO) was studied by using optical difference spectroscopy, c.d. and proton n.m.r. spectroscopy in order to reveal differences in the mode of binding of L-tyrosine and D-tyrosine, which are substrates of but react at different rates with the two peroxidases, to HRP and LPO. All the donor molecules form 1:1 complexes with HRP and LPO, but they display a range of affinities for the enzymes. Whereas D-tyrosine binds to HRP more strongly than does L-tyrosine, the opposite holds for the binding to LPO. The distances of the protons of bound tyrosine molecules from the haem iron atoms of HRP and LPO indicate that the site of binding of these substrates is the same as that of simple phenols. This involves the interaction of the phenol nucleus with a protein tyrosine residue [Sakurada, Takahashi & Hosoya (1986) J. Biol. Chem. 261, 9657-9662; Modi, Behere & Mitra (1989) Biochim. Biophys. Acta 996, 214 225]. However, for the present substrates the additional interaction of the carboxylate group with a protein residue (probably an arginine residue) provides further stabilization for the adducts HRP-D-tyrosine and LPO-L-tyrosine with respect to the corresponding complexes with the opposite enantiomers. The differences in the mode of binding of L-tyrosine and D-tyrosine to HRP and LPO is thus determined by the fact that the spatial arrangement of the interacting protein residues can recognize the chirality of the C(alpha)-CO2- and C(beta) C6H4OH attachment bonds of the substrates. PMID- 1930143 TI - Rat gastric mucin is synthesized and secreted exclusively as filamentous oligomers. AB - Oligomeric gastric mucin was isolated from the fundic part of the rat stomach. Previously we have shown by biochemical analysis that this oligomeric mucin consists of disulphide-linked homo-oligomers, which contain no other covalently attached proteins [Dekker, Aelmans & Strous (1991) Biochem. J. 277, 423-427]. Electron-microscopic images of the oligomeric mucin revealed a heterogenous population of long filamentous molecules of 300-3000 nm length. After reduction and carboxymethylation the monomeric mucins displayed a length distribution with a single peak at about 279 nm. Length-distribution analysis of oligomeric molecules with length up to 1000 nm revealed three subpopulations with one, two or three times the length of the monomeric mucin. The oligomers displayed small globular domains of about 15 nm, which were equally spaced along the molecule's length. As the distance between these globular domains was similar to the monomer length, these domains most likely indicate attachment sites of the monomers. These results show that the mucin monomers attached end-to-end in the oligomer. Biosynthesis of the mucin oligomers was studied by labelling of stomach explants in vitro with [35S]methionine, [3H]galactose or [35S]sulphate and subsequent immunoprecipitation of the mucin with a specific antiserum. Analysis by electrophoresis and gel filtration revealed that the oligomerization takes place by formation of disulphide bonds between the 300 kDa mucin precursors. The mucin was exclusively synthesized and secreted as fully glycosylated oligomers, as neither precursor proteins nor monomeric mucin were detected in the culture medium. A model for the biosynthesis of rat gastric mucin is proposed in which the filamentous mucin monomers are linked end-to-end by disulphide bonds. PMID- 1930144 TI - Pentraxin binding to isolated rat liver nuclei. AB - The interaction of human C-reactive protein (CRP) and serum amyloid P-component (SAP) with isolated rat liver nuclei was studied to identify nuclear ligands for each pentraxin using the iodinatable heterobifunctional thiol-cleavable cross linking reagent sulphosuccinimidyl-2-(p-azidosalicylamido)-1,3'-dithiopropio nate (SASD). Nuclei (100 micrograms of DNA) bound 21 pmol of 125I-labelled CRP Ca(2+) dependently at saturation with half-saturation occurring at 200 pmol of 125I-CRP. By contrast, only 2.7 pmol of 125I-labelled SAP was bound at saturation, with half-saturation at 50 pmol. The binding of pentraxins to nuclei is, in addition to putative chromatin binding, due to nuclear-envelope binding, where 3.2 pmol 125I-labelled CRP binds Ca2+ dependently to nuclear envelopes (25 micrograms) at saturation, but only 0.62 pmol SAP is required to saturate. Specific photocross linking of 125I-2-(p-azidosalicylamido)-1,3'-dithiopropionate (125I-ASD)-CRP and 125I-ASD-SAP to nuclei revealed transfer of 125I-photoreactive azides to nuclear envelope proteins of 43, 46, 52 and 70 kDa. In addition, SAP binding to histones H2A, H2B, H3 and H4 was detected, whereas CRP bound only to H4. Neither pentraxin cross-linked to histone H1. PMID- 1930145 TI - Non-enzymic glycation of human extracellular superoxide dismutase. AB - The secretory enzyme extracellular superoxide dismutase (EC-SOD) is in plasma heterogenous with regard to heparin-affinity and can be divided into three fractions, A that lacks affinity, B with intermediate affinity and C with high affinity. The C fraction forms an equilibrium between the plasma phase and heparan sulphate proteoglycan on the surface of the endothelium. In vitro EC-SOD C could be time-dependently glycated. The enzymic activity was not affected in glycated EC-SOD, but the high heparin-affinity was lost in about half of the studied glycated fraction. Addition of heparin decreased the glycation in vitro, and EC-SOD C modified with the lysine-specific reagent trinitrobenzenesulphonic acid could not be glycated in vitro. The findings suggest that the glycation sites are localized rather far away from the active site and may occur on lysine residues in the heparin-binding domain in the C-terminal end of the enzyme. The proportion of glycated EC-SOD in serum of diabetic patients was considerably higher than in normal subjects. Of the subfractions, EC-SOD B was by far the most highly glycated, followed by EC-SOD A. EC-SOD C was glycated only to be a minor extent. The findings suggest that glycation is one of the factors that contribute to the heterogeneity in heparin-affinity of plasma EC-SOD. Since this phenomenon is increased in diabetes, the cell-surface-associated EC-SOD may be decreased in this disease, increasing the susceptibility of cells to superoxide radicals produced in the extracellular space. PMID- 1930146 TI - N.m.r. determination of the solution conformation and dynamics of the A.G mismatch in the d(CGCAAATTGGCG)2 dodecamer. AB - A.G base-paired mismatches that occur during replication are among the most difficult to detect by repair enzymes. Such purine.purine mispairs can exist in two conformations, one of which is stabilized by protons [Gao & Patel (1988) J. Am. Chem. Soc. 110, 5178-5182]. We have undertaken a 1H-n.m.r. and 31P-n.m.r. study of the mismatched dodecamer d(CGCAAATTGGCG)2 as a function of both temperature and pH to determine the conformational features of the A.G mismatch. At pH greater than 7 the mispaired bases are each in the anti conformation and are stacked in the B-like helix. As the pH is decreased, a second conformation becomes populated (apparent pKa approx. 5.9) with concomitant changes in the chemical shifts of protons of the mispaired bases and their nearest neighbours. Data from two-dimensional nuclear-Overhauser-enhancement spectroscopy show unequivocally that, at low pH, the dominant conformation is one in which the mismatched G residues are in the syn conformation and are hydrogen-bonded to the A residues that remain in the anti conformation. Residues not adjacent to the A.G sites are almost unaffected by the transition or the mispairing, suggesting considerable local flexibility of the unconstrained duplexes. Despite the bulging of the mispaired bases, the conformation of the A(anti).G(anti) duplex is very similar to the native dodecamer, whereas the AH+(anti).G(syn) duplex shows a greater variation in the backbone conformation at the mismatched site. According to the chemical shifts, the duplex retains twofold symmetry in solution. The equilibrium between the syn and anti conformations of G9/G21 is strongly dependent on pH, but only weakly dependent on temperature (delta H approx. 16 kJ.mol-1). The first-order rate constant for the transition is approx. 9 s-1 at 283 K and approx. 60 s-1 at 298 K, with an activation enthalpy of approx. 100 kJ.mol-1. The stabilization of the A(anti).G(syn) conformation by protons is consistent with models invoking N1 protonation of adenine. Using the derived glycosidic torsion angles we have used restrained molecular dynamics to build models of the neutral and protonated d(CGCAAATTGGCG)2 oligomers. The results confirm that the A(anti).G(anti) and AH+(anti).G(syn) conformations are favoured at high pH and low pH respectively, in accord with n.m.r. and single-crystal X ray data. PMID- 1930147 TI - Polarized secretion of tyrosine-sulphated proteins and free tyrosine O-sulphate by filter-grown Madin-Darby canine kidney (MDCK) cells. AB - Filter-grown Madin-Darby canine kidney (MDCK) cells labelled for 24 h with [35S]sulphate were found to secrete macromolecules [35S]sulphated on their carbohydrate moieties predominantly into the basolateral medium, whereas the tyrosine-[35S]sulphated proteins synthesized were predominantly secreted into the apical medium. In contrast with the predominant apical secretin of tyrosine [35S]sulphated proteins, the free tyrosine O-[35S]sulphate (Tyr[35S]) was released mostly into the basolateral medium. A time-lapse study using prelabelled MDCK cells incubated in fresh medium revealed that, during the 48 h time course monitored, the release of tyrosine-[35S]sulphated proteins into the apical medium was faster and quantitatively greater than that into the basolateral medium. During the same time there was a concomitant release, predominantly into the basolateral medium, of the free Tyr[35S] derived from the degradation of tyrosine [35S]sulphated proteins. An endocytotic degradation experiment was performed to demonstrate the endocytosis of tyrosine-sulphated proteins and their degradation to generate free TyrS. It was found that free Tyr[35S] was generated and released when an apically secreted (or basolaterally secreted) tyrosine-[35S]sulphated protein preparation was added to the apical medium (or the basolateral medium) of unlabelled filter-grown MDCK cells. In both cases, the free Tyr[35S] generated was predominantly released into the basolateral medium similar to the results obtained in the time-lapse study. PMID- 1930148 TI - High-density lipoproteins induce a rapid and transient release of Ca2+ in cultured fibroblasts. AB - Several different cell types showed increased rates of proliferation and cholesterol mobilization in response to treatment with high-density lipoprotein (HDL). This would suggest that one main function of HDL is the activation of signal pathways in cells. In the current study we have used the fluorescent indicator fura-2 to monitor the level of cytosolic Ca2+ ([Ca2+]i) in human skin fibroblasts. Exposure of subconfluent as well as confluent fibroblasts to HDL3 (20-60 micrograms/ml) resulted in a rapid and transient increase in [Ca2+]i. Sequential additions of HDL3 resulted in diminished rises in [Ca2+]i. The transient rise in [Ca2+]i was observed with HDL prepared from plasma either by conventional ultracentrifugation or by precipitation with dextran sulphate. Chelation of the extracellular Ca2+ with EGTA prior to the addition of HDL3 did not prevent the HDL3-induced rise in [Ca2+]i, suggesting that the mobilized Ca2+ was derived mainly from intracellular stores. Covalent modification of the apoproteins of HDL3 with dimethyl suberimidate or tetranitromethane did not inhibit the HDL3-induced rise in [Ca2+]i. This indicates that the binding of HDL3 to cell surface receptors may not be necessary for the mobilization of intracellular Ca2+. Moreover, the Ca(2+)-releasing effect of HDL3 was not inhibited by the presence of albumin (1%, w/v) in the extracellular medium, suggesting that non-esterified fatty acids were not the cause of the increased [Ca2+]i. The exposure of fibroblasts to lysophosphatidic acid, a potent mitogen and Ca(2+)-releasing agent, before addition of HDL3 completely inhibited the HDL3 induced rise in [Ca2+]i. Furthermore, phorbol 12-myristate 13-acetate blocked the HDL3-induced rise in [Ca2+]i. The results of this study imply that exposure of cells to HDL generates an intracellular signal which is induced by a component of the lipid fraction. PMID- 1930149 TI - Acyl-chain specificity of human milk bile-salt-activated lipase. AB - In order to probe the active-site structure of human milk bile-salt-activated lipase (BAL), the kinetics of the BAL-catalysed reaction were studied using monoesters as substrates. Among the fatty acyl chains, ranging from C8 to C16 of monoacylglycerols in a single equimolar assay mixture, there was a consistent trend of increased reactivity with decreased fatty-acyl-chain length for both the basal and taurocholate-stimulated activities of BAL. In addition, the detection of hydrolysis of long-chain monoacylglycerols in the absence of bile salt indicates that it is possible for the long-chain fatty acid monoester to form an enzyme-substrate complex with the basal form of BAL. I further examined the reaction kinetics of BAL with water-soluble short-chain esters of p-nitrophenol. The results indicated that there is a consistent trend towards a decreased Michaelis-Menten constant with increased acyl-chain length. Therefore it was concluded that the decreased reactivity with increased acyl-chain length of acylglycerols is probably not a consequence of the lowered affinity of the substrate for the enzyme. The fact that butyrate ester has the optimum acyl chain to be a substrate of BAL can be attributed to its acyl-chain length being long enough for interaction with the active centre of BAL and short enough to provide adequate positioning of the ester bond for transition state complex formation. The calculated free energy of BAL catalysis based on the derived kinetic parameters provides additional insight into the effect on the enzyme-substrate interaction of increasing the number of methylene groups in the acyl chain of substrates. PMID- 1930150 TI - Myosin heavy-chain mRNA is present in both myofibrillar and subsarcolemmal regions of muscle fibres. AB - Hybridization in situ with riboprobes to the myosin heavy-chain slow isoform showed that, in the rat soleus muscle, the myosin heavy-chain mRNA was distributed throughout the myofibres. There was greater density of autoradiographic grains in the subsarcolemmal regions of the fibres, but there was also a considerable number of grains in the core myofibrillar region of the fibres. Microdensitometry showed that the grain density in the myofibrillar region was approximately half that in the subsarcolemmal rim; this would correspond to some 70% of the mRNA being present in the myofibrillar region. The results are consistent with the hypothesis that myosin is synthesized on polyribosomes present in the intermyofibrillar cytoplasm. PMID- 1930151 TI - Expression of epidermal growth factor and its mRNA in pig kidney, pancreas and other tissues. AB - The levels of epidermal growth factor (EGF) mRNA in a wide range of pig tissues were measured by a RNAase-protection assay. The highest levels were found in kidney and pancreas, with lower levels in submaxillary gland, prostate gland and seminal vesicles. Immunocytochemical staining using an antiserum raised against recombinant pig EGF localized expression of the factor to the distal convoluted tubules of the kidney and to the epithelial cells lining the pancreatic and salivary ducts. The observed expression of EGF mRNA and EGF in pig tissues is consistent with a possible role for EGF in the maintenance and repair of the epithelial lining of various ductal systems. PMID- 1930152 TI - Inhibition of neural phospholipase D activity by aminoglycoside antibiotics. AB - The effects of aminoglycoside antibiotics on phospholipase D (PLD) activity were investigated in permeabilized NG108-15 cells and in isolated rat brain membranes. Neomycin inhibited guanosine 5'-[gamma-thio]triphosphate-stimulated PLD activity in digitonin-permeabilized NG108-15 cells in a concentration-dependent manner (50% inhibition at 100 microM). Neomycin similarly inhibited PLD activity present in rat brain membranes and assayed in vitro with [3H]phosphatidylcholine as substrate (50% inhibition at 65 microM). Other aminoglycosides tested (kanamycin, geneticin and streptomycin) were nearly equipotent inhibitors of rat brain PLD. These results indicate that aminoglycoside antibiotics inhibit phosphatidylcholine-PLD activity with comparable and sometimes greater potency than their well known inhibition of phosphoinositide-phospholipase C. The possibility that PLD inhibition could mediate some of the toxic side effects of aminoglycosides is suggested. PMID- 1930153 TI - The identification and purification of the heterotrimeric GTP-binding protein from squid (Loligo forbesi) photoreceptors. AB - The principal GTP-binding protein (G-protein) from squid (Loligo forbesi) photoreceptor membranes has been identified by amino acid sequencing. The heterotrimeric protein was purified by detergent solubilization and ion-exchange chromatography. The amino acid sequence of the G-protein alpha-subunit (G-alpha) indicates that this subunit is closely related to the recently characterized Gq subgroup, whereas the G-gamma subunit varies widely in sequence from other homologues. PMID- 1930155 TI - Calculation of control coefficients of metabolic pathways. A flux-oriented graph theoretic approach. AB - Within the premises of the flux-oriented theory of Crabtree & Newsholme [(1987) Biochem. J. 247, 113-120], I have used a graph-theoretic approach for calculating the Control Coefficients of metabolic pathways. It is shown that a directed graph representing the control structure of a metabolic pathway can be constructed in a heuristic manner directly from the reaction diagram of the pathway, without the necessity of writing down the governing equations for the Control Coefficients. The Control Coefficients are derived from an analysis of the topology of the directed graph. The graph-theoretic approach also provides a visual framework for analysing the functional relationships of the individual enzymes. The control structures of the following pathways are examined here: (a) a simple unbranched pathway with four enzymes, (b) a simple branched pathway with three enzymes, and (c) a branched pathway with both carbon and energy (ATP) fluxes. PMID- 1930154 TI - Polymerase and hydrolase activities of Bacillus subtilis levansucrase can be separately modulated by site-directed mutagenesis. AB - The levansucrase (sucrose:2,6-beta-D-fructan 6-beta-D-fructosyltransferase, EC 2.4.1.10) structural gene from a Bacillus subtilis mutant strain displaying a low polymerase activity was sequenced. Only one missense mutation changing Arg331 to His was responsible for this modified catalytic property. From this allele we created new mutations by directed mutagenesis, which modified the charge and polarity of site 331. Examination of the kinetics of the purified levansucrase variants revealed that transfructosylation activities are affected differently by the substitution chosen. His331----Arg completely restored the properties of the wild-type enzyme. The most striking feature of the other variants, namely Lys331, Ser331 and Leu331, was that they lost the ability of the wild-type enzyme to synthesize levan from sucrose alone. They were only capable of catalysing the first step of levan chain elongation, which is the formation of the trisaccharide ketose. The variant His331----Lys presented a higher kcat. for sucrose hydrolysis than the wild-type, and only this hydrolase activity was preserved in a solvent/water mixture in which the wild-type acted as a true polymerase. The two other substitutions reduced the efficiency of transfructosylation activities of the enzyme via the decrease of the rate of fructosyl-enzyme intermediate formation. For all variants, the sucrose affinity was slightly affected. This strong modulation of the enzyme specificities from a single amino acid substitution led us to postulate the hypothesis that bacterial levansucrases and plant fructosyltransferases involved in fructan synthesis may possess a common ancestral form. PMID- 1930156 TI - Purification and characterization of endoglucanase Ss from Clostridium thermocellum. AB - The extracellular cellulolytic enzymes of the thermophilic anaerobe Clostridium thermocellum occur as a protein complex or aggregate known as the cellulosome. By using a combination of ion-exchange, adsorption and hydrophobic-interaction chromatography, it was possible to isolate from extracellular broth a specific endoglucanase of interest without the use of denaturants. The endoglucanase was identified as the cellulosomal subunit Ss by the use of specific antibodies. The enzyme has an Mr of 83,000, an isoelectric point of 3.55, optimum pH of 6.6 and optimum temperature of 70 degrees C. It hydrolyses CM-cellulose and, at a higher rate, the cellodextrins, cellotetraose and cellopentaose, but does not hydrolyse a crystalline cellulose such as Avicel. Cellobiose and cellotriose are also immune to attack. It differs from endoglucanases previously isolated by others and a 76,000-Mr endoglucanase recently isolated in this laboratory. PMID- 1930157 TI - The kinetics of substrate-induced inactivation. AB - The kinetics of a branched-pathway mechanism for a simple enzymic reaction were studied. In this mechanism there is reversible formation of an inactive form of the second complex along the pathway. This substrate-induced inactivation typically results in the progress curve showing a burst. Three parameters can be obtained from the progress curve: the initial rate, the final rate and the rate constant characterizing the transient. The rate constant for the conversion of the inactive form of the complex into the active form can be obtained either from these parameters or by measuring the regain of enzymic activity. The partition ratio can also be obtained from the three parameters; this is the ratio of the rate of conversion of complex into product to the rate of conversion of complex into inactive form. Simulations give guidance to the conditions required for accurate determinations of the rate constants. PMID- 1930158 TI - Dictyostelium transiently expresses eight distinct G-protein alpha-subunits during its developmental program. AB - Guanine nucleotide-binding proteins (G-proteins) play important roles in signal transduction and in controlling the developmental program of Dictyostelium discoideum. While five G-protein alpha-subunits have been identified in this organism, several lines of evidence suggest that additional G-proteins exist. Using the polymerase chain reaction technique, we have isolated three novel G protein alpha-subunit genes. The predicted amino acid sequences of these PCR fragments are very similar to other Dictyostelium G-protein alpha-subunits in the conserved regions and share little homology outside of those regions. Northern blot analysis indicate that each of these genes has very distinct pattern of expression during development. The possible roles of these G-protein alpha subunits are discussed. PMID- 1930159 TI - The processing of Alzheimer A4/beta-amyloid protein precursor: identification of a human brain metallopeptidase which cleaves -Lys-Leu- in a model peptide. AB - A search for human brain peptidases with the specificity to cleave the 695 residue A4/beta amyloid precursor protein within the -Gln-Lys-Leu- (611-613) sequence was carried out using carbobenzoxy-Gln-Lys-Leu-p-nitroanilide as substrate. A metalloendopeptidase was identified in the soluble fraction of post mortem human cerebral cortex which cleaves the substrate at the Lys-Leu bond. The enzyme was partially purified by anion exchange and size exclusion chromatography; it has a Mr of approximately 105-120 kda, is inhibited by EDTA but can be reactivated by Mn++ ions, and has maximum activity between pH 6.8 and 8. PMID- 1930160 TI - A forskolin and verapamil sensitive K+ current in human tracheal cells. AB - A voltage-dependent K+ current has been revealed in whole-cell recordings carried out on immortalized cells obtained from the human tracheal epithelium. At positive membrane potentials the current shows a time dependent inactivation which is accelerated by increasing the depolarizing step. Forskolin, a direct activator of adenylyl cyclase, and verapamil, a Ca2+ channel blocker, induce the K+ current to inactivate more rapidly. Control experiments show that the action of these two compounds is not mediated by cyclic AMP and Ca2+. The application of 1,9-dideoxyforskolin, an analogue which does not stimulate adenylate cyclase, inhibits the current in the same way as forskolin; on the contrary, the dibutyryl analogue of cyclic AMP is ineffective. Furthermore, eliminating extracellular Ca2+ does not affect K+ current kinetics. Tetraethylammonium is an effective blocker of this current with an IC50 of 0.3 mM. PMID- 1930161 TI - Cultured hepatocytes bind and internalize bovine serum amine oxidase-gold complexes. AB - Cultured hepatocytes express binding sites for bovine serum amine oxidase on their membrane surfaces as evaluated at the electron microscopic level by using enzyme-gold complexes. Hepatocytes show binding sites as small clusters of gold granules, not bound in a specialized region of the plasma membrane. The binding competition of enzyme-gold ligand to cells was achieved by preincubation with uncoupled bovine serum amine oxidase. In addition, N-acetyl-galactosamine, N acetyl-glucosamine and Mannose, at the final concentration of 80 mM, partially inhibit the binding. PMID- 1930162 TI - Defect of a fiber cell-specific 94-kDa protein in the lens of inherited microphthalmic mutant mouse Elo. AB - Deficiency in a 94,000-dalton protein in the non-crystallin fraction from the Elo mouse lens was shown. To perform further investigations, we raised an antibody against the 94,000-dalton protein isolated from normal mouse lens. Western blot analysis with the antibody indicated that the protein was only present in the lens and not in the brain, lung, heart, liver, and kidney. In the lens, it was unique to the cortex and nucleus fractions, not being present in the epithelial cells. Furthermore, it was observed in the water-soluble fraction as well as in the urea-soluble fraction. The antibody weakly but clearly reacted with the chick CP97 lens peptide, a fiber cell-specific protein, and anti-CP97 antibody also reacted with the 94,000-dalton protein. From these results, we concluded that the protein corresponds to CP97 cytoskeletal protein in the mouse lens. The protein was deficient in the lenses from Elo mice, but microphthalmic lenses from CTA mice contained a normal level. PMID- 1930163 TI - Sequence requirements for proteolytic cleavage of precursors with paired basic amino acids. AB - When expressed in COS cells, human prorenin was secreted into the medium without being processed to an active renin. Co-expression of furin, a mammalian homologue of the yeast KEX2 gene product, did not affect proteolytic processing of prorenin. A mutant proreninR-4 constructed by site-directed mutagenesis of Pro ( 4) to Arg was not cleaved by an endoprotease in the COS cell. However, proreninR 4 was detectably cleaved to yield the active renin upon co-transfection with furin DNA, indicating that Arg at position -4 is important for recognition and processing by furin in addition to the absolute requirement for paired basic amino acids. Another mutant precursor in which Leu (+1) of proreninR-4 was replaced with Ser was found to be much more efficiently processed than proreninR 4, regardless of co-expression of furin. The results suggest that not only a basic amino acid at position -4 but also Leu at position +1 significantly affect the processing of prorenin catalyzed by the COS cell endoprotease or furin. PMID- 1930164 TI - Effect of extracellular ATP level on flow-induced Ca++ response in cultured vascular endothelial cells. AB - Cultured vascular endothelial cells loaded with the highly fluorescent Ca(++) sensitive dye Fura-2 were exposed to the flow of a fluid containing various concentrations of ATP (0, 0.5, 1, 5 microM) in an apparatus designed on the basis of fluid dynamics, and simultaneous changes in intracellular free Ca++ concentration were monitored by photometric fluorescence microscopy. The flow rate of the perfusate was altered from 0 to 6.3 to 22.8 to 39.0 cm/sec, inducing shear stress on the cell surface of 0, 2.9, 10.4, and 17.9 dynes/cm2, respectively. Although no significant change in intracellular Ca++ level was observed at ATP levels below 100 nM, at an ATP level of 500 nM, the intracellular Ca++ level increased together with an increase in the flow rate of the perfusate. At this level of ATP, the intracellular Ca++ levels at flow rates of 0, 6.3, 22.8, and 39.0 cm/sec were 44.8 +/- 7.3, 60.3 +/- 10.7, 74.0 +/- 5.8 and 89.4 +/- 6.4 nM (mean +/- SD; n = 8), respectively. At ATP levels over 1 microM, the flow rate dependency of Ca++ response became less clear than that observed at the ATP level of 500 nM. These Ca++ responses to changes in flow rate disappeared when extracellular Ca++ was chelated by adding 2 mM of EGTA to the perfusate. These results suggest that the vascular endothelial cell has a mechanism that elevates the intracellular Ca++ level in accord with the flow rate at appropriate ATP concentrations, and that changes in intracellular Ca++ level under this mechanism seem to be chiefly caused by the influx of extracellular Ca++ into cells. PMID- 1930165 TI - T7 infection-dependent selective expression of cloned genes in P1-lysogenic Escherichia coli. AB - Expression systems based on the selective transcription of genes cloned behind a T7 promoter, by T7 RNA polymerase, display a non-negligible basal expression when the T7 RNA polymerase gene is present within the host organism before induction of the system. This is a problem, especially for cloning and controlled expression of genes toxic to the host organism. We have circumvented this problem by taking advantage of abortive T7 infection of E. coli (P1), in the course of which T7 RNA polymerase is synthesized but bacterial growth is not quantitatively impaired. We have tested this system with three reporter genes, the 6-phospho beta-galactosidase gene of Staphylococcus aureus, the luciferase operon of Vibrio harveyi, and the rabbit beta-globin gene; we have found very low basal levels, while, upon T7 infection, transcription is at least as efficient as in other in vivo T7 RNA polymerase systems in use. PMID- 1930166 TI - Structure-function studies of designed DDT-binding polypeptides. AB - An artificial 24-residue DDT-binding polypeptide (Moser, R., Thomas, R.M., and Gutte, B. (1983) FEBS Lett. 157, 247-251) and several analogues of this peptide were characterized by ligand binding, spectroscopic, and immunological studies. Comparison of dissociation constants showed that Phe14 and His16 were important for DDT binding and that the designed peptide had noticeable ligand specificity. Measurement of the circular dichroism of the artificial DDT-binding peptide revealed a high proportion of beta-structure which was abolished only partly by 8 M urea. When Tyr15, Tyr17, and Phe3 whose side chains were on the same side of the proposed beta-sheet were replaced by non-aromatic amino acids, the cross reactivity with antibodies against the original DDT-binding peptide decreased stepwise. In summary, the results of this study support essential features of our structural model of the designed 24-residue DDT-binding peptide. PMID- 1930167 TI - Cloning of fish zinc-finger genes related to Krox-20 and Krox-24. AB - Southern hybridization suggests that the zebrafish genome contains multiple zinc finger genes related to the putative mouse developmental genes, Krox-20 and Krox 24. The polymerase chain reaction was employed to amplify and clone the zinc finger regions of genes related to Krox-20, from two fish species and, for comparison, mouse, hamster and fox. DNA sequence analyses suggest that the genes cloned include the guppy homologue of Krox-20 and the zebrafish homologue of Krox 24, and that these genes diverged prior to the separation of the lineages leading to teleosts and to mammals. PMID- 1930168 TI - Signal transduction in Coprinus congregatus: evidence for the involvement of G proteins in blue light photomorphogenesis. AB - This paper reports the presence of several G proteins and light-sensitive GTP binding proteins in the fungus Coprinus congregatus, a filamentous eukaryote. (Mono)ADP-ribosylation experiments with crude membranes in the presence of the (poly)ADP-ribosyltransferase inhibitor, 3-amino-benzamide, resulted in the detection of a cholera toxin substrate of 52 kDa and two pertussis toxin substrates, 33 and 39 kDa. Two-dimensional polyacrylamide gel analysis of GTP binding proteins exposed in vivo to [35S]-labeled guanosine 5'-[gamma-thio] triphosphate in the presence or absence of light demonstrated light enhanced analog binding. These results support the concept of the involvement of G proteins in phototransduction in C. congregatus. PMID- 1930169 TI - Expression of c-myc proto-oncogene during podophyllotoxin induced IW32 erythroleukemia cell differentiation. AB - The effect of hemin or podophyllotoxin on the differentiation of the erythropoietin (epo)-producing IW32 erythroleukemia cells was investigated. Podophyllotoxin induced IW32 cells to differentiate, and hemin potentiated the differentiation. Hemin had no effect on cell proliferation whereas podophyllotoxin inhibited cell growth. c-myc mRNA levels decreased biphasically by hemin or podophyllotoxin, while the combined treatment of hemin plus podophyllotoxin did not result in the initial decrease in c-myc mRNA level. Our data suggested that down-regulation of c-myc expression was not a prerequisite of IW32 cell differentiation induced by hemin and podophyllotoxin combined. PMID- 1930170 TI - Determination of the 5' exon structure of the human cardiac alpha-myosin heavy chain gene. AB - We have deduced the exon structure of the 5' untranslated region of the human cardiac alpha-myosin heavy chain gene by cloning a cDNA for this region using the polymerase chain reaction. Comparison of the cDNA and genomic DNA sequences demonstrates that the 5' non-coding region of the alpha-myosin heavy chain gene is interrupted by two introns of 645 and 337 nucleotides. Secondly we have identified the transcriptional start-site by primer extension, corroborating the previous putative assignment for the alpha-myosin heavy chain promoter based on comparisons between the rat and human genes. PMID- 1930171 TI - Reversible inhibition of the urea cycle and gluconeogenesis by N,N-diethyl-m toluamide. AB - Addition of DEET to suspensions of rat hepatocytes completely abolished synthesis of urea from ammonia and production of glucose from lactate. Both activities were fully restored after cells were washed and resuspended in DEET-free medium. These results suggest the DEET-induced impairment is a reversible biochemical defect at a site common to both pathways. PMID- 1930172 TI - Thyroid hormone regulation of alpha-myosin heavy chain promoter activity assessed by in vivo DNA transfer in rat heart. AB - We have studied the thyroid-hormone responsiveness of the alpha-myosin heavy chain (MHC) gene in vivo by directly injecting an expression vector containing the alpha-MHC 5' regulatory sequences (-613 to +421 base pairs) into the rat heart. In the expression vector pAM1Luc the alpha-MHC promoter elements direct the synthesis of firefly luciferase. Although thyroxine administration of both euthyroid and thyroidectomized rats for 5 days increased alpha-MHC promoter activity, the pAM1Luc gene construct did not mimic expression of the endogenous gene. These studies of direct gene transfer into mammalian myocardium suggest that additional cis-acting elements necessary for the in vivo response to thyroid hormone reside outside the -613 to +421 region. PMID- 1930174 TI - Proteoglycan and glycosaminoglycan free chain expression in keratinocytes, endothelium, and mesenchymal cells. AB - Cultured fibroblasts, bovine aortic endothelial cells, and human keratinocytes synthesize both proteoglycans and glycosaminoglycan free chains, the proportions varying between cell types. The major metabolic labeling is in proteoglycans, except for keratinocytes with approximately 60% of product as free chains. The proteoglycans range from approximately 50- greater than 1000 kDa, and the glycosaminoglycan side chains derived by alkaline elimination are approximately 30- greater than 100 kDa. The glycosaminoglycan free chains, in contrast, are smaller, from approximately 7-40 kDa in mass. The proteoglycans are both medium and cell layer constituents, whereas the glycosaminoglycan free chains are essentially confined to cells. The cellular proteoglycans and a portion of the free chains are accessible to in situ digestion by Flavobacterial glycosaminoglycan lyases, presumably reflecting localization to the cell surface. Collectively, the data show the free chains to be a common feature of all cells studied and to be partly expressed on cell surfaces. We hypothesize that the processing that creates these free chains occurs on cell surfaces, in which location they could serve ligand receptor functions. PMID- 1930173 TI - Triamcinolone acetonide inhibits lymphocyte differentiation in B cells decorated with artificial antigen receptors. AB - We examined the effects of triamcinolone acetonide (TA) on T cell independent antigen-induced differentiation of human B cells. Purified human B cells artificially decorated with palmitate-conjugated monoclonal IgA antibody specific for 2,4-dinitrophenyl differentiated polyclonally when challenged with optimum concentrations of dinitrophenyl-derivatized polymerized flagellin. This B cell response was reduced by the synthetic corticosteroid TA at a concentration of 10( 6) M. This suggests that TA can inhibit in vitro B lymphocyte differentiation independent of T cells. PMID- 1930175 TI - Signal and propeptide processing of human tissue plasminogen activator: activity of a pro-tPA derivative. AB - We have explored the heterogeneity in the proteolytic processing of the N terminus of human tissue plasminogen activator. We demonstrate that normal propeptide processing occurs following Arg-4, preceding the sequence Gly-Ala-Arg Ser+1. Generation of the previously designated Ser+1 occurs via secondary proteolysis following secretion. By site-directed mutagenesis, we have eliminated this cleavage site resulting in a derivative containing the propeptide sequence. N-terminal sequence analysis of this form indicated that signal peptide cleavage occurs following Ser-13. The pro-tPA derivative had near normal serine protease and plasminogen activating activities, and could be stimulated by fibrin. An additional derivative, containing the tribasic sequence from the human protein C propeptide preceding Ser+1, was secreted with full processing of the propeptide. Our data have defined the cleavages for the signal peptide and propeptide and demonstrate that a tribasic sequence can be used to eliminate N-terminal heterogeneity in this molecule. In addition, we demonstrate that, unlike several other serine proteases, a propeptide sequence does not alter the activity of this enzyme. PMID- 1930177 TI - A high phosphorylation state and increased activity of the TRE motif in the NIH3T3 cell transformant induced by retTPC. AB - A 57 kDa protein was detected in an NIH3T3 transformant induced by retTPC, an activated form of the ret proto-oncogene which encodes a receptor-tyrosine kinase. A high phosphorylation state and increased activity of a TPA responsive element was observed in the transformant. Increased expression of c-jun mRNA was also detected. A 40 kDa protein in the retTPC transformant, which was specifically immunoprecipitable with v-jun antiserum, was highly phosphorylated mainly at a serine residue(s). These data suggest that an aberrant signal triggered by a retTPC product affects the cellular serine/threonine phosphorylation state resulting in high phosphorylation of c-jun protein. PMID- 1930178 TI - NMR studies of fluorinated visual pigment analogs. AB - The 19F-nmr chemical shift data of isomeric pigments (11-cis and 9-cis) of four vinyl fluororhodopsins and two trifluororhodopsins have been recorded. When compared with model protonated Schiff bases, a set of F-nmr opsin shift parameter (FOS) was obtained. The data revealed regiospecific protein perturbations on the F-resonances. They can be interpreted in terms of specific protein interactions such as the postulated second point charge and other polar interactions as well as the common hydrophobic protein perturbation. PMID- 1930176 TI - Stimulation of in vivo tumor growth and phorbol ester-induced inflammation by N,N diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine HCl, a potent ligand for intracellular histamine receptors. AB - We have implicated histamine as a mediator of proliferation through its binding to novel intracellular receptors (HIC), closely associated with antiestrogen binding sites (AEBS) in microsomes and nuclei. N,N-diethyl-2-[4 (phenylmethyl)phenoxy]ethanamine HCl (DPPE), is a potent ligand for AEBS/HIC. We now demonstrate that DPPE stimulates in vivo tumor growth (DMBA-induced mammary cancer in Sprague-Dawley rats and L5178Y leukemia in DBA/2 mice) and synergizes with phorbol-12-myristate-13-acetate (PMA) to induce inflammation and mitotic activity in mouse epidermis. Thus, ligands for intracellular histamine receptors may represent a new class of tumor promoting agents; this finding lends new credence to an important role for histamine in growth. PMID- 1930179 TI - Microfluorometric size measurements of human and phage DNA correlate with the degree of in vitro cisplatin treatment. AB - The anticancer drug cisplatin is shown to inhibit the proofreading activity of the enzyme T4 polymerase. A microfluorometric assay that can measure the relative sizes of cisplatin treated human and phage DNA, after exposure to T4 polymerase, is described. Using phage DNA size standards, it is shown that the mean integrated fluorescent density (IFD) of fluorophore labeled DNA is linearly correlated with molecular size. Exonuclease digestion by T4 polymerase of cisplatin treated lambda DNA gave fragment sizes whose mean IFD was proportional to the degree of platination. This method of size measurement was then applied to DNA from human carcinoma cells that had been cultured untreated, cisplatin and/or 5-fluorouracil treated. Platination resulted in exonuclease digestion fragments whose mean IFD value was significantly larger than controls (p less than 0.0006). This technique of relative size measurement appears potentially promising for the clinical analysis of altered DNA in cell populations after treatment with cytotoxic agents. PMID- 1930180 TI - Characterization of a second promoter for the mouse liver/bone/kidney-type alkaline phosphatase gene: cell and tissue specific expression. AB - The second leader exon and the relative promoter of the mouse liver/bone/kidney type alkaline phosphatase gene were identified and characterized. The transcription initiation site was determined by S1 mapping analysis. The differential expression of the two alternatively spliced transcripts was assessed in cell lines of different origin and in various tissues by polymerase chain reaction and RNase mapping analysis. The first promoter is active in embryo derived cells, whereas the second promoter is silent in basal conditions but it is activated by dibutyryl cAMP in fibroblastic cells. In the whole animal, the transcript driven by the first promoter is found in most tissues albeit at different levels, while the one driven by the second promoter is specifically expressed at high levels only in the heart. PMID- 1930181 TI - Changes in expression of angiotensin receptor subtypes in the rat aorta during development. AB - Quantitative autoradiography was used to characterize angiotensin AT1 and AT2 receptors, in the rat aorta at three developmental ages; embryonic day 18 (E18), and postnatal weeks 2 and 8. The expression of angiotensin receptors was higher in the aorta of E18 and 2-week-old rat. A major proportion of the angiotensin receptors expressed in the aorta at these two ages was AT2 (84 and 81% respectively). Conversely, in the aorta of 8-week-old rats, AT1 was the predominant angiotensin receptor subtype (71%). In 8-week-old rats, the AT2 subtype was also present (28%). In pre- and postnatal rats, [125I]Sar1 angiotensin II binding to AT1 receptors was sensitive to GTP gamma S whereas binding to AT2 receptors was not. AT2 receptors may serve an important role during stages of rapid growth of the aorta, and also have a significant function in the adult vasculature. PMID- 1930182 TI - Generation and fate of enamines in the microsomal metabolism of cyclic tertiary amines. AB - Microsomal oxidation of 1-benzylpiperidine (1-BP) and its cis-2,6-dimethyl analog was studied to assess the involvement of endocyclic enamines, in equilibrium with the initially formed iminiums, in the metabolic activation of cyclic tertiary amines such as phencyclidine. Since the iminiums can be trapped with cyanide, the selective prevention by cyanide of the metabolic production of 1-benzyl-3 piperidone from 1-BP implicates the iminium in equilibrium with enamine as the source of this metabolite. In cases where iminium-enamine coupling is sterically prevented, the iminium in equilibrium with enamine species can be studied independently and are found to be more potent metabolism-dependent inactivators of cytochrome P-450 than are the corresponding parent amines. Possible mechanisms for biological oxidation of cyclic enamines to reactive intermediates are considered. PMID- 1930183 TI - Isolation and characterization of an infectious molecular clone of the MN strain of HIV-1. AB - Infectious molecular clones of the human immunodeficiency virus (HIV) have been very important tools for the analysis of regulatory gene functions and the study of differential cell tropism. We have cloned and characterized a proviral sequence of HIVmn from mn strain infected H9 cells. This clone, called KP1, was found to be infectious for different cell lines and human peripheral blood lymphocytes (PBL). KP1 proviral DNA was detected in HUT-78 cells and human PBL by polymerase chain reaction (PCR) analysis after infection of these cells with cell free supernatants from KP1 transfected human rhabdomyosarcoma (RD) cells. To the best of our knowledge, this is the first report of an infectious molecular clone of HIVmn which is a representative of one of the most prevalent strains of HIV-1 in North America and Europe. Biologically active clones of a broadly antigenic strain such as HIVmn will be extremely useful in therapeutic approaches for AIDS. PMID- 1930184 TI - Current inactivation involves a histidine residue in the pore of the rat lymphocyte potassium channel RGK5. AB - RGK5 is a rat genomic DNA clone that encodes the n-type potassium channel found in T-lymphocytes and other cells. Current through this channel declines (inactivates) over a period of hundreds of milliseconds during a maintained depolarizing pulse, whether in lymphocytes or when expressed in Xenopus oocytes. Here we demonstrate that an amino acid residue near the outer pore of the channel, histidine401, is involved in the inactivation process. Replacement of this residue by tyrosine, the amino acid found in the equivalent position of the homologous but non-inactivating channel RBK1, reduced inactivation of RGK5 over a 5 s depolarizing pulse from 84.3 +/- 1.9% to 18.3 +/- 1.1%. Conversely, replacement of this tyrosine in RBK1 (Tyr379) by histidine increased its inactivation from 21.6 +/- 1.1% to 42.3 +/- 1.5%. These results suggest a mechanism of channel inactivation distinct from that previously described for the A-type potassium channel. PMID- 1930185 TI - Quantitation of GLUT1 and GLUT4 mRNA using a solution hybridization assay. AB - The development of a solution hybridization assay for detecting GLUT1 and GLUT4 mRNA is described. The details of this assay are described in which copy RNA is used to quantitate messenger RNA in total RNA samples. This solution hybridization assay is highly specific and reproducible and is significantly more sensitive than Northern blotting. Since GLUT mRNAs can be quantitated in as little as 25 mg tissue, this technique is essential when the supply of tissue is limited. Furthermore, the elimination of gel-based separation techniques allows for mRNA quantitation in several hundred samples within two days following isolation of samples. PMID- 1930186 TI - Chromosomal assignment of the human immunophilin FKBP-12 gene. AB - FKBP-12 is the major T cell binding protein for the immunosuppressive drugs FK506 and rapamycin. It is a member of the immunophilin family of proteins which are believed to play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. The chromosomal assignment of the human FKBP-12 gene was determined by using the polymerase chain reaction to amplify an intron-containing region of the gene in purified DNA isolated from 42 human-rodent somatic cell hybrids. The results of this analysis indicated that the FKBP-12 gene resides on human chromosome 20. PMID- 1930187 TI - Synthesis and characterization of a Pertussis toxin-biotin conjugate. AB - We prepared a Pertussis toxin-biotin conjugate and found its biological properties to be similar to those of native Pertussis toxin with respect to the hemagglutination, Chinese hamster ovary cell, and lymphocyte proliferation assays. Direct binding to Chinese hamster ovary and Jurkat cells was observed using fluorescence microscopy. Pertussis toxin-biotin was also found to possess similar glycoconjugate binding specificities as those of 125I-labeled Pertussis toxin. PMID- 1930188 TI - Cloning and tissue expression of a rat histamine H2-receptor gene. AB - We have screened a rat genomic library using DNA probes derived from the sequence of a recently cloned canine histamine H2 receptor (Gantz et al., Proc. Natl. Acad. Sci. USA 1991, 88, 429-433). An intronless gene, encoding a 358 amino acid protein displaying all major features of G protein-coupled receptors and a 82% overall homology with the canine histamine H2 receptor, was isolated. Northern blot analysis, performed with a probe derived from the rat sequence, revealed a single approximately 6.0 kb transcript in various rat tissues. In the brain, this transcript is highly expressed in brainstem and, to a lesser extent, cerebral cortex, striatum, hippocampus and hypothalamus. These localizations are consistent with the distribution of the H2 receptor in this species. Among peripheral tissues, the stomach highly expresses the transcript which could not be detected in various other organs. All these features, together with the expression of the cloned gene in mammalian cells (Traiffort et al., submitted), are consistent with the idea that a single rat H2 receptor is encoded by the cloned gene. PMID- 1930189 TI - Mammalian spermatid specific protein, TP2, is a zinc metalloprotein with two finger motifs. AB - An analysis of the recently reported cDNA derived amino acid sequences of mouse (Kleene and Flynn, J. Biol. Chem. 262, 17272-17277, 1987) and rat (Luersson et al., Nucl. Acids Res. 17, 3585, 1989). TP2 has revealed the presence of two potential zinc finger motifs involving cysteine and histidine residues. TP2, as purified from rat elongating spermatids, is shown here to contain 0.2 atoms of zinc bound per molecule of the protein by atomic absorption spectroscopy. On incubation with 10 microM ZnCl2, in vitro, and subsequent exhaustive dialysis, TP2 had 2 atoms of zinc bound per molecule. The involvement of cysteine residues of TP2 in coordination with zinc was also suggested by the observation that TP2 could be labeled, in situ, with iodoacetamidofluorescein only after preincubation of spermatid nuclei with EDTA. The zinc finger domains of TP2 may play an important role in initiation of chromatin condensation and/or cessation of transcriptional activity during mammalian spermiogenesis. PMID- 1930190 TI - Inhibition of the thrombin-platelet reactions by DuP 714. AB - The efficacy and specificity of a novel synthetic thrombin inhibitor, DuP 714, on thrombin-induced elevation of cytoplasmic calcium, fibrinogen binding and aggregation in human platelets were examined. Thrombin (0.5 U/ml) stimulated an increase in [125I]fibrinogen binding in gel-filtered platelets which was blocked by DuP 714 with an IC50 value of 2 nM. Thrombin (1 U/ml)-induced elevation of intracellular [Ca2+]i was also blocked by DuP 714 with an IC50 value of 67 nM. A much higher concentration of thrombin (25 U/ml) was used to stimulate aggregation with heparinized platelet-rich plasma. Under these conditions, micromolar concentrations of DuP 714 were needed to inhibit thrombin. In all of these preparations, DuP 714 at concentrations as high as 10(-5) M had no intrinsic effects and did not affect the responses induced by arachidonate, ADP, collagen, epinephrine, vasopressin and serotonin. These data indicate that DuP 714 is a potent and specific thrombin inhibitor capable of arresting the actions of thrombin on human fibrin formation and platelet aggregation and secretion. It may serve as a potential antithrombotic agent for various forms of thrombotic disorders. PMID- 1930191 TI - Inhibitory effect of cadmium and mercury ions on transcription of the ada gene. AB - The effect of Cd2+ and Hg2+ on transcription of the ada gene was examined using an in vitro system reconstituted with Ada protein and methylated DNA, together with their effect on methyltransferase activity of the Ada protein. Both Cd2+ and Hg2+ inhibited transcription of the ada gene over the doses which did not inhibit methyltransferase activity. PMID- 1930193 TI - Creatine kinase BB produced by murine hybridomas but not by parental cells. AB - Creatine kinase BB is the main CK isoenzyme expressed in murine hybridoma cells as assessed by agarose gel electrophoresis whereas it was found neither in splenocytes nor in myeloma cells. The presence of CK BB is a constant finding in all 10 murine hybridomas examined to date irrespective of the specificity of the secreted antibodies. PMID- 1930192 TI - Arachidonic acid and diacylglycerol act synergistically to activate protein kinase C in vitro and in vivo. AB - Using a well-defined model membrane bilayer system, incorporation of both lipid second messengers, 1,2-diacylglycerol and arachidonic acid, at submaximal activating concentrations, resulted in a synergistic activation of protein kinase C in a Ca2+/phosphatidylserine-dependent manner as measured by monitoring phosphorylation of phosphoprotein substrates. The arachidonic acid appears to modulate membrane properties both at the hydrocarbon core and the membrane surface increasing the availability of the diacylglycerol which can bind to and subsequently activate the enzyme. Co-application of these two lipid activators to the Hermissenda photoreceptor reduced K+ channel conductance in a synergistic manner via a PKC-dependent pathway. Thus, these in vivo and in vitro studies suggest that the membrane bilayer properties of these PKC lipid activators interact to specifically regulate the cellular lipid microenvironment resulting in PKC activation. PMID- 1930194 TI - Rabbit antibodies against two different extracellular domains of human thyrotropin receptor possess thyroid stimulating activities. AB - We have produced rabbit antibodies against synthetic peptides corresponding to the mid-region (amino acid residues 172-202, C peptide) and to the unique segment near the transmembrane region (amino acid residues 341-370, P peptide) in the extracellular component of the human thyrotropin (TSH) receptor and evaluated their biological activities. Both anti-C peptide antibodies raised in two rabbits showed strong thyroid stimulating activities (TSAb) (4127% and 2548%). Anti-P peptide antibodies raised in two rabbits were also strongly positive for TSAb activities (359% and 3468%). However, none of these antibodies had TSH-binding inhibitor immunoglobulin (TBII) activities. These results suggest that the domains responsible for TSAb are likely to span the entire extracellular component of the TSH receptor. PMID- 1930195 TI - Membranolytic and nucleolytic activities of cytolytic T lymphocyte clones. AB - In an attempt to see if the nucleolytic and membranolytic activities of cytolytic T lymphocytes (CTL) were totally independent and could be expressed independently, we cloned CTL and determined their membranolytic and nucleolytic activities. If the two lytic mechanisms were completely independent and could be independently expressed by individual CTL, we anticipated that we would find CTL clones exhibiting only one or the other activity. Initial examination of membranolytic and nucleolytic activities in 99 newly established CTL clones revealed a poor correlation (r = 0.4) between the two activities. In addition, some clones expressed membenolytic activity without nucleolytic activity, and others, nucleolytic activity without membenolytic activity. The results suggest that CTL have 2 or more separate and independent mechanisms that lead either to the membranolytic or to the nucleolytic lesions in target cells. PMID- 1930196 TI - Glycosylation is essential for efficient secretion but not for permeability enhancing activity of vascular permeability factor (vascular endothelial growth factor). AB - The hyperpermeability of the microvasculature supplying solid tumors is largely attributable to a heterodimeric Mr 34,000-43,000 tumor-secreted protein, vascular permeability factor. Upon reduction, the vascular permeability factor secreted by line 10 tumor cells is resolved by SDS-PAGE into 3 discrete bands of Mr 24,000, 19,500, and 15,000. We demonstrate here that line 10 vascular permeability factor is an N-linked glycoprotein. Nonglycosylated vascular permeability factor migrates on reduced SDS-PAGE as two bands of Mr 20,000 and 15,000. Pulse-chase studies demonstrated that all three chains of native vascular permeability factor were secreted rapidly following synthesis and at equal rates, with a cellular half-retention time of approximately 37 min. When glycosylation was prevented by tunicamycin, individual bands of nonglycosylated vascular permeability factor were also secreted at equivalent rates, but much more slowly (approximately 60 min) than native glycoprotein. Both glycosylated and nonglycosylated forms of vascular permeability factor were equally potent at increasing dermal vessel permeability. PMID- 1930197 TI - Lipoprotein-incorporated pregnenolone fatty acid esters act as substrate for ovarian progestin synthesis. AB - Progesterone is of great importance in the normal development of the ovarian follicle and its biosynthesis has been shown to rely on plasma low-density lipoproteins for delivery of cholesterol substrate. However, the pre-ovulatory ovarian follicle has no access to plasma low-density lipoproteins suggesting that other substrates may be involved in pre-ovulatory progestin production. We show in this study using tritiated pregnenolone fatty acid esters incorporated into lipoproteins can give rise to a series of labelled progestins following lipoprotein-mediated internalization. In doing so, progestins are synthesized by shunting the accepted rate limiting step of steroidogenesis, the intracellular P450 side chain cleavage pathway. Furthermore, we demonstrate that follicular fluid high density lipoproteins contain vast endogenous concentrations of this lipoidal pregnenolone metabolite which may indeed contribute to progesterone production in the pre-ovulatory ovarian follicle. PMID- 1930198 TI - Nonreducible crosslink formation in tibial dyschondroplastic growth plate cartilage from broiler chicks fed homocysteine. AB - In the study of tibial dyschondroplasia, scientists have for a long time thought that an altered extracellular matrix might be involved in the etiology of the disease. The results presented in this paper show that the collagen content was increased in the dyschondroplastic cartilage when compared to normal growth plate and day-old hypertrophic cartilage. Furthermore, nonreducible crosslinks were found only in dyschondroplastic cartilage, with the greatest amounts occurring in the distal region of the lesion, approximately 10-fold higher than that found in the dyschondroplastic growth plate. Thus, intermolecular collagen bonding is altered in the extracellular matrix of dyschondroplastic cartilage. Possible models for the etiology of the disease are discussed. PMID- 1930199 TI - Separation of the two domains of human mucus proteinase inhibitor: inhibitory activity is only located in the carboxy-terminal domain. AB - Human mucus proteinase inhibitor is a two-domain protein which inactivates bovine trypsin and chymotrypsin, leukocyte elastase and cathepsin G. In order to localize the site(s) responsible for these inhibitory activities, the two domains were isolated after specific cleavage of the Asp49-Pro50 bond following mild acid treatment of the bronchial inhibitor. The carboxy-terminal domain was active against leukocyte elastase, trypsin and chymotrypsin whereas the amino-terminal domain, which contained a putative antitryptic active site, was devoid of activity. This implicates that, in the whole molecule, the inhibitory activity region is localized only in the carboxy-terminal domain. PMID- 1930200 TI - Inhibition of pre-mRNA splicing by antisense RNA in vitro: effect of RNA containing sequences complementary to introns. AB - The objective of the experiments described in this paper was to test the potential of antisense RNAs complementary to the internal portion of an intron to inhibit the splicing process and to determine the mechanism of such inhibition. The results obtained indicate that RNA fragments complementary to the internal portion of an intron can effectively inhibit the splicing of pre-mRNA. Inhibition was observed only with antisense RNA complementary to pre-mRNA suggesting that the inhibitory effect was due to the formation of a hybrid with the corresponding portion of the pre-mRNA's intron. The observed inhibition was not due to interference with possible intron elements essential for the splicing process, for the deletion of the sequences complementary to inhibitory antisense RNA from the corresponding pre-mRNA molecule did not affect the efficiency of a splicing reaction, and the addition of antisense RNA to pre-mRNA mutants carrying such deletions did not result in any inhibition. Our results indicate that the observed inhibition is a function of the length of the antisense RNA expressed as a fraction of an intron with which it interacts when antisense RNA is modified by incorporation of a "hinge" element, it loses its inhibitory potential suggesting that the inhibitory effect is probably due to limitation of conformational flexibility of an intron. PMID- 1930201 TI - Phosphorothioate analogues of oligodeoxyribonucleotide: synthesis and activity as inhibitors of replication of human immunodeficiency virus. AB - The modifications of oligodeoxyribonucleotides include replacement of the other chain either all-PS (S-ODNs), or end-capped with several PS (SO-ODNs) groups at both 3'- and 5'-ends. A general synthesis of phosphorothioate analogues of oligodeoxyribonucleotides is described using the new phosphite. In assays of HIV, oligomers (S-ODNs) with complete replacement of phosphodiesters with phosphorothioate groups were found to be very active. Finally of particular interest is S-ODNs-rev or tat (20mers) which possessed slightly higher anti-HIV activity than S-dC28 itself. By contrast, the unmodified oligomers (ODNs) as well as SO-ODNs did not have any inhibitory effect. PMID- 1930202 TI - Substitution of asparagine for serine-406 of the immunoglobulin mu heavy chain alters glycosylation at asparagine-402. AB - Previous work suggested that the substitution of Asn for Ser at position 406 of the mu heavy chain of mouse IgM results in aberrant glycosylation at Asn402. In order to characterise the apparently abnormal glycosylation process more precisely, the mutant and wildtype mu chains were fragmented by cleavage with cyanogen bromide, and the resulting glycopeptides were analysed further. Measurements of lectin binding specificity as well as glycosidase sensitivity suggest that the oligosaccharide at Asn402 of wildtype mu is a hybrid type which does not contain terminal alpha(2-6) or alpha(2-3) linked sialic acid. By contrast, the corresponding oligosaccharide on Asn402 of mutant mu is complex and contains terminal sialic acid linked alpha(2-6) to galactose. The structural features for specifying the abnormal glycosylation are present in monomeric mutant IgM. PMID- 1930203 TI - Involvement of OP18 in cell proliferation. AB - Op18 is a highly conserved major cytosolic phosphoprotein that is expressed at high levels in acute leukemia and in neuroblastoma. In this study we present evidence pointing to a role for Op18 in cellular proliferation. Blocking of Op18 mRNA translation using antisense oligonucleotides delayed entrance of mitotically stimulated normal peripheral blood lymphocytes into the S phase. Moreover treatment of HL-60 promyelocytic leukemia cells with DMSO or PMA which induced terminal differentiation resulted in a decrease in the level of Op18 RNA and protein. Inhibition of lymphoid proliferation with cyclosporin also resulted in reduced Op18 levels. PMID- 1930204 TI - Delta 12-prostaglandin J2 mimics heat shock in inducing cell cycle arrest at G1 phase. AB - Using a human neuroblastoma cell line GOTO, the effects of delta 12-prostaglandin (PG) J2 on the modulation of cell cycle progression and protein synthesis were examined in comparison with those caused by heat shock (HS). delta 12-PGJ2 induced G1 arrest, the peak of which was obtained at 24 h and continued for 72 h. HS was found to induce G1 arrest earlier than delta 12-PGJ2. Furthermore, sequential HS could maintain G1 arrest. delta 12-PGJ2 induced the synthesis of several heat shock proteins (HSPs) in a manner similar to HS. Using immunoblot analysis, HSP72 was detected prior to inducing G1 arrest and accumulated during the subsequent 72h. The content of HSP72 induced by HS also correlated well with the induction, release, and maintenance of G1 arrest. In addition, both delta 12 PGJ2 and HS induced HSP72 mRNA and simultaneously suppressed N-myc mRNA expression. These results suggest that delta 12-PGJ2 and HS regulate cell cycle progression of GOTO cells via similar mechanisms. PMID- 1930205 TI - "Secretase," Alzheimer amyloid protein precursor secreting enzyme is not sequence specific. AB - The major pathological change in Alzheimer's disease is the deposition of amyloid beta/A4-protein (beta P) in the brain. beta P is derived from a small part of the much larger amyloid protein precursor (APP). In the normal condition, APP is cleaved in the interior of beta P, preventing the formation of beta P, by a hypothetical proteinase "secretase". To characterize this enzyme, APP and mutated APPs were expressed by cDNA transfection in COS-1 cells, a monkey kidney fibroblast derived cell line. The mutant APPs with the mutations of the proposed cleavage site (Gln686-Lys687) were processed in the same way as wild APP. The deleted mutant APP (deletion of Arg676-Asp694) was also cleaved in a similar way to wild APP. The cleavage site of this deletion mutant was located at the 12 amino acid residues from the predicted membrane spanning domain. Hence, "secretase" cleaves APP, depending not on its specific amino acid sequence, but probably on the relative conformation with plasma membrane. PMID- 1930206 TI - NW-nitro L-arginine benzyl ester, a potent irreversible inhibitor of endothelium dependent relaxation. AB - In the rat aorta preparation, we have used the nitro-arginine derivative, NW nitro L-arginine benzyl ester (NABE), as a probe to investigate the relationship between L-arginine and the endothelium derived relaxing factor (EDRF). We find NABE to be a potent endothelium dependent vasoconstrictor and inhibitor of relaxation. The effect of NABE is irreversible and not removed by subsequent washing. The vasoconstrictor effect of NABE differs from other EDRF inhibitors like NG-monomethyl L-arginine (L-NMMA) in that it is not antagonized by pre treatment with excess L-arginine. In contrast, like other EDRF inhibitors, at high concentration NABE exhibits vasodilation which is antagonized by methylene blue. We suggest that the previous reports on the antagonism between L-arginine and the putative EDRF inhibitors like L-NMMA are due to their structural similarities rather than to externally added L-arginine acting as a substrate for EDRF synthesis. PMID- 1930207 TI - Effect of dietary manipulation on c-myc RNA expression in adipose tissue, muscle and liver of broiler chickens. AB - The effects of dietary restriction on the relative steady state levels of cellular myc (c-myc) mRNA in abdominal adipose tissue, breast muscle and liver of chickens were determined. Fasting was found to increase c-myc RNA expression in adipose tissue (p less than 0.01). This increase returned to normal levels after refeeding. Muscle and liver in fasted birds did not show changes in c-myc that differed from controls. Serum concentrations of glucose, triglyceride (TG), free fatty acids (FFA) and insulin-like growth factor (IGF-I) were compared to levels of c-myc found in control birds. In adipose tissue, c-myc levels were negatively correlated with serum glucose, TG and IGF-I, while in muscle a positive correlation with serum glucose and TG was found. Data suggest that c-myc is involved in the metabolic changes occurring in fat cells under fasting conditions. PMID- 1930208 TI - Evidence that potassium channels regulate prolactin secretion in GH4C1 cells by causing extracellular calcium influx. AB - Tetraethylammonium (TEA), a K+ channel blocker, induced prolactin (PRL) secretion in GH4C1 cells in a dose-dependent manner when applied at a concentration from 1 20 mM. During continuous exposure to TEA, a significant increase in PRL secretion occurred by 20 min and the response was sustained until the end of a 60-min exposure. Blocking Ca2+ influx by employing a Ca(2+)-depleted medium or the Ca2+ channel blocker, nifedipine, prevented induction of PRL secretion by 20 mM TEA. Preincubation of the cells for 10 min with 20 mM TEA did not inhibit PRL secretion induced by thyrotropin-releasing hormone (TRH), phorbol 12-myristate 13 acetate (TPA) or by cell swelling produced by 30% medium hyposmolarity, but significantly depressed that induced by depolarizing 30 mM K+. BaCl2, another K+ channel blocker, had the same effect on PRL secretion as TEA. The data suggest that blocking K+ channels may cause membrane depolarization, thereby inducing Ca2+ influx which is a potent stimulus for PRL secretion in GH4C1 cells. PMID- 1930209 TI - Inhibition of microtubule assembly is a possible mechanism of action of mitoxantrone. AB - We have found that mitoxantrone can inhibit the polymerization of brain tubulin in a dose dependent manner. MXT had relatively high affinity for tubulin but had no appreciable effect on tubulin associated guanosine-triphosphatase (GTPase) activity nor could it compete with vinblastine (VB) and colchicine (Col) for tubulin binding sites. Furthermore, MXT (0.1-10 microM) is antiproliferative to cold-treated (0 degree C) epithelial cells after only brief exposure (30 min). These results indicated that MXT is a microtubule inhibitory agent and can exert its anticellular effect through modulation of microtubule assembly. PMID- 1930210 TI - A novel vasopressin receptor in rat early proximal tubule. AB - In order to evaluate the receptor subtypes of arginine vasopressin (AVP) in early proximal tubule (S1), outer medullary thick ascending limb of Henle's loop (MTAL) and collecting tubule (OMCT), the effect of AVP on intracellular free calcium ([Ca++]i) was determined using the fluorescence indicator Fura-2. Physiological concentration (greater than or equal to 10(-12) M) of AVP in MTAL and OMCT mobilized [Ca++]i in a dose-dependent manner, but relatively high concentration (greater than or equal to 10(-9) M) of AVP in S1 increased [Ca++]i. Moreover, pretreatment with both V1 and V2 antagonists in MTAL or OMCT completely inhibited the AVP-induced [Ca++]i transient, but in S1 partially blocked it. Using several AVP analogues, a relative distribution of AVP receptor subtypes was tentatively calculated in each nephron segment, indicating that although these nephron segments possess V1, its density was very low (about 10%). The majority (about 90%) of AVP receptor in MTAL and OMCT was V2, while that in S1 was a new subtype (named Vp) which is insensitive to V1 and V2 antagonists. To evaluate physiological significance of Vp receptor, AVP-mediated cellular ATP change was measured. Cellular ATP content in S1 was significantly increased by 10(-7) M AVP, but in MTAL it was significantly decreased by the same concentration of AVP. This study suggests that a novel AVP receptor exists in isolated rat S1, and its physiological significance may be the inhibition of ATP-consuming ion transport system. PMID- 1930211 TI - Alteration of human myoglobin proximal histidine to cysteine or tyrosine by site directed mutagenesis: characterization and their catalytic activities. AB - Two mutant proteins of human myoglobin (Mb) that exhibit altered axial ligations were prepared by site-directed mutagenesis of a cloned gene for human Mb. The normal axial ligand residue, histidine 93(F8), was replaced with cysteine or tyrosine, resulting in H93C or H93Y Mb, respectively. Cysteine or tyrosine coordination to the ferric heme iron is verified by electronic absorption, 1H NMR, EPR spectra, and redox potentials of Fe2+/Fe3+ couple. Their mono oxygenation activities of styrene are also discussed. PMID- 1930212 TI - The human Hb (mu) class glutathione S-transferases are encoded by a dispersed gene family. AB - The human glutathione S-transferases are products of a gene superfamily which consists of at least four gene families. The various glutathione S-transferase genes are located on different human chromosomes, and new gene(s) are still being added to the gene superfamily. We have characterized a cDNA in pGTH4 encoding human glutathione S-transferase subunit 4 (GST mu) and mapped its gene (or a homologous family member) on chromosome 1 at p31 by in situ hybridization. Genomic Southern analysis with the 3' noncoding region of the cDNA revealed at least four human DNA fragments with highly homologous sequences. Using a panel of DNAs from mouse-human somatic cell hybrids in genomic DNA hybridization we show that the Hb (or B) genes of human glutathione S-transferases are on three separate chromosomes: 1, 6, and 13. Therefore, the glutathione S-transferase B gene family, which encodes the Hb (mu) class subunits, is a dispersed gene family. The GST mu (psi) gene, whose expression is polymorphic in the human population, is probably located on chromosome 13. We propose that the GST mu (psi) gene was created by a transposition or recombination event during evolution. The null phenotype may have resulted from a lack of DNA transposition just as much as from the deletion of an inserted gene. PMID- 1930213 TI - Hepatic expression of apolipoprotein A-I gene in rats is upregulated by monounsaturated fatty acid diet. AB - The effect of the degree of dietary fat saturation on the hepatic expression of apolipoprotein A-I mRNA was studied in male rats. Animals were maintained for two months on a high fat diet (40% w/w) containing 0.1% cholesterol. Two groups of control animals received either chow diet or chow plus 0.1% cholesterol, while experimental groups received their fat supplement as coconut, corn or olive oil respectively. Dietary cholesterol did not affect apolipoprotein A-I mRNA levels as compared to control animals. Corn oil fed animals had significantly higher levels of hepatic apolipoprotein A-I mRNA than those receiving cholesterol, or coconut oil plus cholesterol. Olive oil fed animals had significantly higher levels of hepatic apolipoprotein A-I mRNA when compared to all other dietary groups. Our data indicate that monounsaturated fatty acids supplied as olive oil play a major role in regulating the hepatic expression of apolipoprotein A-I in male rats. PMID- 1930214 TI - Substrate analog inhibitors of HIV-1 protease containing phenylnorstatine as a transition state element. AB - Substrates of HIV-1 protease are classified into three groups (A, B and C) based on the amino acid residues present at P1' and P2' sites. Replacement of the scissile amide bond by phenylnorstatine in representative substrate analog sequences from class A, B and C, yielded inhibitors of HIV-1 protease. Of the twelve inhibitors synthesized in this series, class C substrate analog inhibitors are more potent inhibitors (Ki's 3.3-24 microM) than either class A or class B inhibitors. In this series of inhibitors, the (2S,3S) isomer of phenylnorstatine is preferred over the other isomers as a "transition state element" for design of inhibitors of HIV-1 protease. PMID- 1930215 TI - Investigating the stereochemistry of binding to HIV-1 protease with inhibitors containing isomers of 4-amino-3-hydroxy-5-phenylpentanoic acid. AB - A series of inhibitors containing all possible isomers of 4-amino-3-hydroxy-5 phenylpentanoic acid was synthesized and tested for inhibition of HIV-1 protease. Incorporation of the (3S,4S) isomer of the t-butyloxycarbonyl protected amino acid into the sequence Glu-Phe resulted in a potent inhibitor of HIV-1 protease (Ki = 63 nM). This inhibitor is at least 47-times more potent than the inhibitors containing other isomers of 4-amino-3-hydroxy-5-phenylpentanoic acid, indicating that the (3S,4S) isomer is the preferred isomer for binding to HIV-1 protease. PMID- 1930216 TI - Phosphorylation and functional modification of calmodulin-dependent protein kinase IV by cAMP-dependent protein kinase. AB - Calmodulin-dependent protein kinase IV (CaM-kinase IV), a neuronal calmodulin dependent multifunctional protein kinase, undergoes autophosphorylation in response to Ca2+ and calmodulin, resulting in activation of the enzyme (Frangakis et al. (1991) J. Biol. Chem. 266, 11309-11316). In contrast, the enzyme was phosphorylated by cAMP-dependent protein kinase, leading to a decrease in the enzyme activity. Thus, the results suggest differential regulation of CaM-kinase IV by two representative second messengers, Ca2+ and cAMP. PMID- 1930217 TI - Calcium binding to fluorescent calcium indicators: calcium green, calcium orange and calcium crimson. AB - The recently introduced fluorescent calcium sensitive indicators calcium green, calcium orange and calcium crimson suggest important improvements and advantages to detect small calcium transients at low indicator concentrations. Thermodynamic dissociation constants and dissociation rate constants of calcium green, calcium orange and calcium crimson were measured by use of fluorescence titration and stopped flow fluorescence, respectively. Calcium binding to the indicators conforms to a 1:1 calcium:indicator complex although at high concentrations of calcium the fluorescence properties deviate somewhat from the behaviour predicted by the simple model. Dissociation of the calcium-indicator complex was found to be monoexponential under all conditions examined. The affinity for calcium of the three indicators generally increases with raising temperatures (Kd at 11.5 degrees C and 39.7 degrees C (nM): 261, 180 for calcium green; 527, 323 for calcium orange; 261, 204 for calcium crimson) and pH (Kd at pH 6.42 and 7.40 (nM): 314, 226 for calcium green; 562, 457 for calcium orange; 571, 269 for calcium crimson). The changes of the thermodynamic dissociation constant are mainly caused by changes of the association rate constant. The temperature dependence of calcium binding to the indicators revealed that this process is entropically favoured at ambient temperature. PMID- 1930218 TI - Energy state of chondrocytes assessed by 31P-NMR studies of preosseous cartilage. AB - The energy state of resting and hypertrophic chondrocytes from growth plate was studied by 31P-NMR spectroscopy of superfused cartilage slices. The presence of phosphocreatine was demonstrated in both cell types, using a repetition time of 3 s. By comparing the decline in the nucleoside triphosphate level after adding blockers of the glycolysis or of the mitochondrial respiration, it was deduced that resting and hypertrophic chondrocytes use both metabolic pathways for energy production, but the glycolysis dominates. Hypertrophic cells rely more on the mitochondrial respiration than the resting cells. PMID- 1930219 TI - Definition of the affinity of binding between human von Willebrand factor and coagulation factor VIII. AB - Factor VIII and von Willebrand factor are two plasma proteins essential for effective hemostasis. In vivo, they form a non-covalent complex whose association appears to be metal ion dependent. However, a precise definition of the nature of the molecular forces governing their association remains to be defined, as does their binding affinity. In this paper we have determined the dissociation constant and stoichiometry for Factor VIII binding to immobilized von Willebrand factor. The data demonstrate that these proteins interact saturably and with relatively high affinity. Computer assisted analyses of the Scatchard data favour a two site binding model. The higher affinity site was found to have a Kd of 62 (+/- 13) x 10(-12) M while that of the lower affinity site was 380 (+/- 92) x 10( 12) M. The density of Factor VIII binding sites (Bmax) present on von Willebrand factor was 31 (+/- 3) pM for the high affinity binding site and 46 (+/- 6) pM for the lower site, corresponding to a calculated Factor VIII: von Willebrand factor binding ratio of 1:33 and 1:23, respectively. PMID- 1930220 TI - Calcium is required for the reduction of sulfite from hydrogen in a reconstituted electron transfer chain from the sulfate reducing bacterium, Desulfovibrio gigas. AB - Calcium is found a strong stimulator of sulfite reduction from hydrogen. A coupling protein of molecular weight 65,000 can be isolated from Desulfovibrio gigas. It functions in a reconstituted electron transfer chain between hydrogenase and sulfite reductase. Its N-terminal sequence shows high homologies with calcium or magnesium binding sites from other calcium-binding proteins. PMID- 1930221 TI - Cisplatin induces the small heat shock protein hsp25 and thermotolerance in Ehrlich ascites tumor cells. AB - Exposure of Ehrlich ascites tumor (EAT) cells to the anticancer drug cisplatin results in an elevated abundance of three isoforms of the small heat shock protein hsp25 without inducing the general stress response as commonly observed after heat shock. The most effective cisplatin concentration (2.5 microM) is also most efficient in arresting cells in S phase suggesting a relationship between hsp25 expression and cell cycle events. Exposure to cisplatin results also in an increased thermotolerance of EAT cells. PMID- 1930222 TI - Formation and proliferative effects of lipoxins in human bone marrow. AB - Lipoxins A4 and B4 together with the all-trans lipoxin (LX) isomers were produced by normal human bone marrow cell suspensions after incubation with ionophore A23187. Both LXA4 and LXB4 enhanced the growth of myeloid progenitor cells in semisolid agar in the presence of suboptimal concentrations of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Lipoxin A4 at 10(-10) M stimulated the colony formation in 13 out of 15 tested human bone marrows with a mean (+/- SEM) increase of 47 +/- 11% (p = 0.001). A similar stimulatory effect was observed after addition of LXB4 (10(-10) M). The monohydroxyeicosatetraenoic acids 5-, 12- and 15-HETE did not affect colony growth. In addition, LXA4 (10(-8) M) efficiently counteracted the increased colony formation induced by leukotriene C4 (10(-10) M), suggesting an antagonistic relationship between these lipoxygenase products. The results support a role for lipoxins in the regulation of human myelopoiesis. PMID- 1930224 TI - Macrophage hydrogen peroxide production and phagocytic function are decreased following phagocytosis mediated by Fc receptors but not complement receptors. AB - Previous in vivo and in vitro studies have shown that the phagocytosis of IgG coated erythrocytes results in a depression of macrophage function. The present study compared the effect of phagocytosis mediated by Fc receptors with that mediated by complement receptors. The phagocytosis of IgG-coated erythrocytes by elicited peritoneal macrophages depressed their capacity to produce hydrogen peroxide as well as phagocytic function. Phagocytosis of erythrocytes coated with IgM and complement had neither of these effects. These results implicate the intracellular signaling that results from Fc receptor mediated phagocytosis in the depression of macrophage function that is caused by phagocytosis. PMID- 1930225 TI - Correlation between NMR spectral parameters of nucleosides and its implication to the conformation about the glycosyl bond. AB - Analyses of high resolution proton and carbon NMR spectra of a series of guanine nucleosides in DMSO have revealed a near linear correlation between the chemical shift of the H2, atom of the sugar moiety and the vicinal coupling constant 3JC4 H1'. This unexpected result provides evidence that the variations in the glycosyl torsion angle between nucleosides in solution are less that those which have previously been reported in crystals and it is an experimental basis for analyzing the syn and anti populations from chemical shift and coupling constant data. PMID- 1930223 TI - Position-independent, aberrant expression of the human ornithine decarboxylase gene in transgenic mice. AB - We have generated transgenic mouse lines carrying the human ornithine decarboxylase (ODC) gene in their genome. Six of 7 transgenic lines overexpressed ODC in most of their tissues, which was most strikingly manifested as a highly ectopic enzyme activity in the testis and brain of transgenic mice. A close correlation existed between enzyme activity (or ODC mRNA level) and gene copy number in testis and brain, indicating that the expression occurred independently of the transgene's chromosomal integration site. Transgenic mice carrying the mouse ODC promoter fused to the bacterial chloramphenicol acetyltransferase gene expressed the reporter gene in a similarly aberrant fashion. Even though the human ODC gene construct contained 5'-flanking sequences (800 nt), sufficient to confer maximal promoter activity in transfected cells, and about 1000 nt of 3' flanking DNA, it is improbable that the observed gene copy number-dependent expression was due to the presence of so-called DNA attachment elements. In contrast, our data suggest that expression of the mammalian ODC gene is governed by distal silencer elements that were missing in the transgene constructs, which permitted an apparently position-independent expression of the transgene. PMID- 1930226 TI - Equilibrium unfolding of class pi glutathione S-transferase. AB - The equilibrium unfolding transition of class pi glutathione S-transferase, a homodimeric protein, from porcine lung was monitored by spectroscopic methods (fluorescence emission and ultraviolet absorption), and by enzyme activity changes. Solvent (guanidine hydrochloride and urea)-induced denaturation is well described by a two-state model involving significant populations of only the folded dimer and unfolded monomer. Neither a folded, active monomeric form nor stable unfolding intermediates were detected. The conformational stability, delta Gu (H2O), of the native dimer was estimated to be about 25.3 +/- 2 kcal/mol at 20 degrees C and pH6.5. PMID- 1930227 TI - Neutrophil activating peptide-2 binds with two affinities to receptor(s) on human neutrophils. AB - Neutrophil receptor(s) for neutrophil activating peptides 1 and 2 were studied by competition binding experiments with radiolabeled NAP-1 and NAP-2 preparations. NAP-1 bound with one affinity, NAP-2 with two quite different affinities, to common receptor(s) on neutrophils. Concentrations of NAP-2 needed to induce exocytosis of beta-glucosaminidase corresponded to the higher dissociation constant of the two binding equilibria. Thus, the binding of NAP-2 to PMN with high affinity does not activate the cells. PMID- 1930228 TI - Magnetic field elicits hypotension mediated by platelet activating factor in rats injected with iron beads. AB - Rats injected intravenously with iron beads (avg. diameter 3.4 microns; 1 g/kg body weight) were exposed to static or time-varying magnetic fields (400 gauss) for 5 min, which elicited a marked and rapid decrease in the mean arterial blood pressure (52 +/- 7 mmHg, mean +/- SE), lasting for 1-2 h. Hypotension was prevented or reverted by the platelet activating factor (PAF) antagonist SRI 63 675. The release of PAF from iron-loaded phagocytes may be due to magneto orientational effects on membranes. This novel magnetic bioeffect can also be used for the study of PAF-mediated circulatory shock. PMID- 1930229 TI - The single cysteine residue on an alpha family chick liver glutathione S transferase CL 3-3 is not functionally important. AB - Chick liver glutathione S-transferase CL 3-3, expressed using a baculovirus system in Spodoptera frugiperda (SF9) cells, contains a single cysteine residue per subunit. This enzyme was modified with iodoacetamide. Amino acid analysis indicates that 0.85 +/- 0.10 cysteine residue was modified per enzyme subunit. GST CL 3-3 modified with iodo[14C]acetamide was further digested with trypsin and the isotope-labelled fragments were isolated. The fragment containing the cysteine residue accounts for 53% of the total labels. The S-carbaminomethylated protein retains the glutathione conjugating activity. Therefore, the cysteine residue is not essential for the enzymatic activity of CL 3-3. PMID- 1930230 TI - Phosphorylation and chromatin mechanics: the central importance of substrate conformation in determining the patterns of HL-60 nuclear phosphorylation. AB - HL-60 nuclear autophosphorylation was studied in vitro under circumstances in which the conformation of chromatin was manipulated with both polyamines and DNAse-I. A general re-arrangement of the phosphorylation patterns occurred as polyamines were removed and nuclei were observed to expand. DNAse-I treatment reduced these phosphorylation patterns to a much simpler configuration indicating that the responding substrates were DNA-associated. It was concluded that substrate conformation was the main determining factor in the control of nuclear protein phosphorylation. These results suggest a method of general utility for the identification of truly nuclear proteins by the characteristics of their phosphate acceptor activity. PMID- 1930231 TI - The nonspecific inner membrane pore of liver mitochondria: modulation of cyclosporin sensitivity by ADP at carboxyatractyloside-sensitive and insensitive sites. AB - Cyclosporin A prevents the opening of a nonspecific pore in the inner membrane of liver mitochondria when added prior to Ca2+. In the presence of 10 microM Ca2+ cyclosporin is unable to close the pore and restore the original permeability unless ADP is also added. ADP acts at a high-affinity site (Km 5 microM), corresponding to the adenine nucleotide transporter. This effect of ADP is prevented and reversed by carboxyatractyloside. In the presence of carboxyatractyloside, cyclosporin added with higher concentrations of ADP (Km 70 microM) also can close the pore. This suggests that a lower-affinity ADP-binding component as well as cyclophilin and the adenine nucleotide transporter can modulate the sensitivity of the pore to cyclosporin. PMID- 1930233 TI - GLUT 1-glucose transporter protein in adult and fetal mouse lung. AB - We observed approximately 45-50 kD GLUT 1 protein in mouse lung homogenates and demonstrated a greater abundance in fetus compared to adult. In situ immunohistochemical analysis demonstrated GLUT 1 expression only in the perineural sheath of nerves. While the trapped fetal red blood cells expressed GLUT 1 abundantly, adult red blood cells were devoid of GLUT 1. No GLUT 1 was evident in fetal and adult lung alveolar and bronchiolar epithelial cells, vascular endothelial cells and the lung mesenchymal elements. Thus, GLUT 1 is not the major lung glucose transporter. PMID- 1930232 TI - Structural identity of immunoglobulin binding factor and prostatic secretory protein of human seminal plasma. AB - The amino acid sequence of the N-terminus of the immunoglobulin binding factor of human seminal plasma was determined. The initial 30 amino acids showed complete identity with that of prostatic secretory protein, beta-microseminoprotein and beta-inhibin. In conclusion, these proteins are probably a single entity. PMID- 1930234 TI - In situ binding of fatty acids to the liver fatty acid binding protein: analysis using 3-[125I]iodo-4-azido-N-hexadecylsalicylamide. AB - A photoactivatable radioiodinated fatty acid analogue, 3-[125I]iodo-4-azido-N hexadecylsalicylamide (125I-AHS) has been synthesized and used to investigate the involvement of cellular lipid carriers in hepatic fatty acid utilization. Photoactivation of Hep G2 internalized 125I-AHS revealed that several cellular proteins were crosslinked with the radiolabeled fatty acid analogue. Three predominant proteins in the membrane fraction of the cell with molecular masses 17, 50 and 127 kDa were crosslinked with the lipid analogue, as determined using autoradiography after SDS-PAGE. Three other proteins in the soluble fraction of the cell, with molecular masses 14, 24 and 35 kDa, were also labeled in situ. In contrast to the other labeled proteins, the fatty acid analogue accumulated on the cytoplasmic 14 kDa protein in a time and temperature dependent fashion. The in situ-labeled 14 kDa protein was identified from primary rat hepatocytes as the liver fatty acid binding protein by partial purification and its ability to be immunoprecipitated with immunospecific L-FABP antiserum. Collectively the results indicate that fatty acids traverse the plasma membrane and are bound cytoplasmically by the liver fatty acid binding protein, as well as other proteins in the cell. This represents the first demonstration in intact hepatocytes that the liver fatty acid binding protein participates in the process of intracellular fatty acid trafficking, and supports a model in which cytoplasmic lipid carriers solubilize fatty acids as a step in their metabolic utilization. PMID- 1930235 TI - Utilization of methoxylated aromatic compounds by the acetogen Clostridium thermoaceticum: expression and specificity of the co-dependent O-demethylating activity. AB - The aromatic CO-dependent O-demethylating activity of Clostridium thermoaceticum was evaluated. Secondary aromatic substituent groups (-OH, -CO2H, -CH2OH, and OCH3) were critical to O demethylation. O-demethylating activities and specificities were similar from cells grown at the expense of different methoxylated aromatic compounds; all O-methyl-grown cells catalyzed the same sequential O demethylation of multi-methoxylated compounds, suggesting that a broad specificity O demethylase was involved in O demethylation. In cell fractionation studies, CO-dependent O demethylation was catalyzed by membrane associated components. PMID- 1930237 TI - Purification of 52 kDa protein: a putative component of the import machinery for the mitochondrial protein-precursor in rat liver. AB - A protein having a molecular mass of 52 kDa was purified to homogeneity from solubilized mitochondrial membrane proteins by affinity column chromatography using the synthetic presequence of ornithine aminotransferase (OAT) as the ligand. This 52 kDa protein was specifically bound to the affinity column and eluted with 1 mM OAT-presequence, indicating that it recognized the presequence and bound to it specifically. Anti-52 kDa protein Fab fragments specifically inhibited the import of OAT-precursor into mitochondria, showing that the 52 kDa protein plays an essential role in this process. These results suggest that 52 kDa protein is a component of the import machinery of the mitochondrial protein precursor in the mitochondrial membrane. PMID- 1930236 TI - Detection of 20-hydroxyeicosatetraenoic acid in rat urine. AB - 20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonate metabolite of the cytochrome P450 omega hydroxylase, was detected in rat urine by gas chromatography-mass spectrometric techniques. The concentration of 20-HETE in urine from 7-week-old hypertensive and normotensive rats was 2.1 and 1.3 nM, respectively. This is the first demonstration of 20-HETE urinary excretion and thus calls attention to the possibility that 20-HETE participates in the regulation of renal function via its effect on vascular tone and ion transport processes. PMID- 1930238 TI - Gastrin releasing peptide-like immunoreactive substance in rat mammary glands during pregnancy. AB - The concentration of gastrin releasing peptide-like immunoreactive substance (GRP IS) was measured by enzyme immunoassay (EIA) in rat mammary glands during pregnancy and after delivery. The GRP-IS concentration was high in the middle stage of pregnancy (10-14 days of gestation) and decreased in late pregnancy to reach a plateau range. By using HPLC, it was shown that GRP(20-29) and GRP(16-29) were mainly present in rat mammary glands. Immunohistochemical study revealed that epithelial cells of rat mammary glands were stained intensely with antiserum GP-6201. These results suggest that GRP-IS is produced and secreted in epithelial cells of mammary glands and takes part in the proliferation, differentiation and hypertrophy of mammary glands. PMID- 1930239 TI - Cytokine- and forskolin-induced synthesis of group II phospholipase A2 and prostaglandin E2 in rat mesangial cells is prevented by dexamethasone. AB - We have previously described that treatment of rat glomerular mesangial cells with interleukin-1 beta, tumor necrosis factor or forskolin stimulates the synthesis and secretion of prostaglandin E2 and group II phospholipase A2. We now report that pretreatment of the mesangial cells with dexamethasone dose dependently suppresses the cytokines- and forskolin-induced synthesis of prostaglandin E2 as well as the induced synthesis and secretion of group II phospholipase A2. These observations implicate that the inhibition of the cellular or secreted phospholipase A2 activity by dexamethasone in rat mesangial cells is not due to induced synthesis of phospholipase A2 inhibitory proteins but caused by direct inhibition of phospholipase A2 protein expression. PMID- 1930240 TI - Localization of an endogenous ADP-ribose acceptor, p33, in polymorphonuclear cell granules in chicken liver interlobular connective tissue. AB - We investigated immunohistochemically the localization of p33, an endogenous substrate protein for an arginine-specific ADP-ribosyltransferase in chicken liver. Polymorphonuclear-pseudo-eosinophilic granulocytes (heterophils) in interlobular connective tissues of the liver were exclusively and strongly stained with the antibody against p33. Strong reactivity was associated with granules in cytoplasm of the heterophils. When the chicken liver nuclear fraction was washed, the transferase activity was released into the 600 x g supernatant fraction while a nuclear enzyme poly(ADP-ribose) synthetase was retained in the pellet fraction. These results indicate that p33 and probably also ADP ribosyltransferase, found in the liver nuclear fraction [Tanigawa et al. (1984) J. Biol. Chem. 259, 2022-2029, Mishima et al. (1988) Eur. J. Biochem. 179, 267 273], originate from interlobular heterophils of the chicken liver. PMID- 1930241 TI - Thromboxane A2 synthesis in human erythroleukemia cells. AB - Human erythroleukemia cells transformed arachidonic acid and prostaglandin endoperoxide H2 into thromboxane A2. Stimulation of these cells with A23187 or thrombin, however, produced no thromboxane. Similarly, cells labeled with [3H] arachidonic acid released no detectable label upon stimulation. Data suggest that human erythroleukemia cells contain the enzymatic capacity for thromboxane formation from exogenous precursors, but lack the endogenous mechanisms for arachidonate release. The presence of thromboxane synthase messenger RNA was verified using the polymerase chain reaction. Amplification and sequence analysis of a 528 bp cDNA demonstrated virtually 100% identity to a published thromboxane synthase cDNA fragment. PMID- 1930242 TI - In vivo activation of an omega-6 oxygenase in human skin. AB - To test the hypothesis that an epidermal fatty acid oxygenase is activated in vivo under physiologic conditions, surface lipids from normal human skin were analyzed for oxygenase products. With high-performance liquid chromatography on reversed-phase and straight-phase chiral columns and gas-liquid chromatography/mass spectrometry, these lipids were found to contain free 13 hydroxyoctadeca-9Z,11E-dienoic acid and 9-hydroxyoctadeca-10E,12Z-dienoic acid. The 13-hydroxyoctadecadienoic acid was present as a stereoisomeric mixture, with an average S/R ratio of 2.2, and exceeded the concentration of 9 hydroxyoctadecadienoic acid by a factor of 2. These observations and others indicate that the 13-hydroxyoctadecadienoic acid was derived mostly from an omega 6 oxygenase (probably 15-lipoxygenase) which is activated in vivo in normal skin. PMID- 1930244 TI - Human N-acetylgalactosamine-4-sulphatase: protein maturation and isolation of genomic clones. AB - N-Acetylgalactosamine-4-sulphatase (EC 3.1.6.1, G4S) is composed of a 57 kDa species in human liver that dissociates into 43 kDa and 8 kDa subunits under reducing conditions and, when deficient, causes the lysosomal storage disorder, mucopolysaccharidosis type VI. We isolated genomic clones containing the G4S first exon, including the leader peptide and the amino terminus of the 43 kDa polypeptide. Amino-terminal amino acid sequences of the 43 kDa and 8 kDa subunits indicated that the 8 kDa component is linked to the 43 kDa polypeptide by a single disulphide bond, does not contain the mannose-6-phosphate lysosomal targeting signal and is at the carboxyl terminus of G4S. PMID- 1930243 TI - Yeast mitochondria (Saccharomyces cerevisiae) contain Ca(2+)-independent phospholipase A1 and A2 activities: effect of respiratory state. AB - We demonstrate that both phospholipase A1 and phospholipase A2 are associated with isolated yeast mitochondria (Saccharomyces cerevisiae). Activity assays indicate that, unlike most other mitochondrial phospholipases A, the yeast enzymes are Ca(2+)-independent with acidic (pH 4-5) as well as alkaline (pH 8-9) pH optima. Data obtained with mitochondria isolated from either fermenting or respiring cells, and initial observations with a petite strain, strongly suggest that a phospholipase A2 with an acidic pH optimum functions in the in vivo adaptation and maintenance of mitochondrial membranes required for respiration. PMID- 1930245 TI - On the expression of HMG I protein in quiescent and proliferating human T lymphocytes. AB - The results demonstrate that the HMG I protein is expressed in human quiescent T lymphocytes and hence is not dependent upon proliferation or neoplastic transformation. Furthermore it has been found that the HMG I/histone H1 ratio increase about two-fold after activation with phytohemagglutinin and was about the same as in a number of proliferating human leukemia lymphoma T-cell lines. PMID- 1930246 TI - Identification of a possible control element, Mt5, in the major noncoding region of mitochondrial DNA by intraspecific nucleotide conservation. AB - Nucleotide sequences throughout the whole major noncoding region of mitochondrial DNA of 18 subjects were determined. Previously identified control elements were classified into three groups according to the degree of intraspecific nucleotide conservations: strictly conserved elements (LSP, HSP, Mt3, Mt3 on H-strand, mtTF1 element for HSP), relatively conserved elements (CSB-III, Mt4 on H-strand, and mtTF1-element for LSP), and variable elements (TAS, CSB-I, CSB-II). Moreover, alignment of nucleotide conservations disclosed a stretch of conserved sequence (5'-ATGCTTACAAGCAAG-3', nucleotide number 16, 194-16,208, designated as Mt5 element) in the middle of the hypervariable segment. Nucleotide conservation of this element was not only intraspecific but also interspecific. PMID- 1930247 TI - Transport of L-asparagine in Tetrahymena pyriformis ecto-L-asparaginase is not related to L-asparagine-protein transport system. AB - L-Asparaginase of T. pyriformis is a membrane-bound enzyme with an active site situated on the outside surface of the membrane. When radioactive L-asparagine was incubated with T. pyriformis cells in the L-asparaginase assay medium, the hydrolysis was 240 higher than the uptake of this amino acid. In a similar experiment performed in salt medium (Wagner's solution), the hydrolysis was linearly increased and reached after one hour of incubation a value of 60 nmol/10(6) cells, while the uptake after 20 min of incubation reached a plateau with a value of 15 nmol/10(6) cells. The uptake of L-leucine under these conditions was 44 nmol/10(6) cells/hr, while no measurable transport of aspartic acid was observed. That L-aspartic acid is not migrated into T. pyriformis cells is in agreement with the finding that no efflux of this amino acid takes place as well. The uptake of L-asparagine is pH and K+ dependent, whereas Na+ ions strongly inhibit this uptake. The Km and Vmax values of L-asparagine uptake is 1.43 mM and 0.7 nmol/min, respectively. The half life of L-asparagine "protein transport system" was 40 min, a value which is very close to the half life of the membrane-bound L-asparaginase of this microorganism. Ouabain and vanadate inhibit the uptake of L-asparagine by more than 80%, while ouabain or vanadate inhibit in vivo 5% or 95% the activity of L-asparaginase, respectively. This indicates the lack of interrelationship between the L-asparagine "protein transport system" and the L-asparaginase protein molecule. PMID- 1930248 TI - Influence of ethanol on liver and plasma lipid levels during chick embryo development. AB - Ethanol introduced into the air chamber of the egg during the last week of the chick embryonic period did not induce changes in liver or embryo weights. Alcohol dehydrogenase activity increased during the period studied in both ethanol and control groups, however, ethanol significantly inhibited the enzymatic activity. Alcohol administration did not alter plasma or liver cholesterol levels. On the other hand, three days after the beginning of the treatment, ethanol decreases plasma triglyceride levels increasing simultaneously the content of this lipid in the liver. If the ethanol treatment is continued for ten days the opposite occurs. An increase and decrease in liver and plasma triglycerides were observed respectively. These results suggest that ethanol interferes with processes which maintain plasmatic triglyceride levels. PMID- 1930249 TI - Effects of polyene macrolides on the membrane potential of resting and activated human leukocytes. AB - Membrane potential changes in human polymorphonuclear leukocytes have been studied by monitoring the fluorescence signal of a carbocyanine probe in the presence of calcium ionophore A23187, chemotactic tripeptide f-met-leu-phe, and polyene macrolides. Reduction of the signals triggered by the ionophore and the tripeptide, inhibition of the respiratory burst, and changes in the Na+ influx into the cell seem to be the dominant effect of the polyenes. Polyene-induced depolarization does not correlate with the inhibition of the respiratory burst. PMID- 1930250 TI - Isolation and characterization of alpha-1-proteinase inhibitor from goat plasma. AB - Alpha-1-proteinase inhibitor (alpha-1-PI) was isolated from goat plasma by salt fractionation, and chromatography on a DEAE-cellulose column. The inhibitor was found to be homogeneous by gel chromatography, SDS-PAGE and PAGE.Mr values by gel filtration (57 kDa), and by SDS-PAGE (52 kDa), under reducing conditions were nearly the same suggesting that the inhibitor consists of a single polypeptide chain. It contained 13.8% neutral hexose but no sialic acid residue. The values of isoionic pH, and extinction coefficient at 278 nm were 4.84, and 4.6, respectively. Fluorescence spectral properties showed tryptophan residues in the inhibitor. Solvent perturbation difference spectra suggested 74% exposure of the tryptophan residues in the native molecule. Gel filtration behaviour of the inhibitor was consistent with a Stokes radius of 3.16 nm, diffusion coefficient of 7.02 X 10(-7) cm2-sec-1 and a frictional ratio of 1.24 suggesting asymmetry and/or excessive hydration of the inhibitor molecule. Goat alpha-1-PI, unlike human alpha-1-PI was found to be potent inhibitor of bovine trypsin but a poor inhibitor of porcine pancreatic elastase. It was virtually devoid of antichymotryptic activity. PMID- 1930251 TI - Stimulation of L-ornithine uptake and L-citrulline and urea biosynthesis by D arginine. AB - The action of D-arginine on isolated cells and mitochondria obtained from rat liver was studied. The D-amino acid at 200 microM stimulated by 40% the rate of urea biosynthesis by isolated hepatocytes. Citrulline formation was increased 60 70% in rat liver mitochondria incubated with 10 microM D-arginine. In these mitochondria, ornithine uptake was enhanced 204% with 1 microM D-arginine. Inhibition in urea and citrulline synthesis and in ornithine uptake was recorded with high concentrations of the D-amino acid. Respiratory control in liver mitochondria with glutamate-malate was inhibited 32% by 100 microM D-arginine. In isolated mitochondria loaded with Fluo-3-acetoxymethyl (AM) ester, 50 microM D arginine diminished the matrix free calcium concentration. PMID- 1930252 TI - Insulin-like growth factor I-like immunoreactivity in serum and tissues of the tilapia, Oreochromis mossambicus. AB - Tilapia serum was acidified with 0.5 M HCl and then chromatographed on an octadecasily-silica column. After washing with 4% acetic acid, the column was eluted with methanol. The eluate was evaporated to dryness. The sample cross reacted in a human insulin-like growth factor I (IGF-I) radioimmunoassay, suggesting immunochemical similarity to human IGF-I. IGF-I-like immunoreactivity was present at high levels in tilapia liver. Other tissues containing IGF-I-like immunoreactivity included the gonad, kidney, heart, spleen, brain and muscle. The serum IGF-I-like immunoreactivity was attributed to substances with a molecular weight of 9,000 and 45,000 respectively, and it was elevated after treatment with bovine growth hormone and carp pituitary extract. PMID- 1930253 TI - Enhanced expression of heat shock protein and mRNA synthesis by type I interferon in human HL-60 leukemic cells. AB - The effects of IFN and mild hyperthermia on the responses of human promyelocytic HL-60 cells were investigated. Cells subjected to an elevated culture temperature (39.5 degrees-40.5 degrees C instead of 37 degrees C, herein referred to as heat treated cells) showed an increase in heat shock proteins (HSPs) and corresponding mRNA synthesis, which were additionally potentiated by the presence of IFN. With cells cultured at 37 degrees C, IFN had no effect on HSP expression. The observed inhibition (40-70%) of RNA polymerase II-directed RNA synthesis (based on alpha amanitin sensitivity) in isolated nuclei of heat-treated cells was also significantly reversed by the simultaneous addition of IFN. These data suggest that the IFN-amplified HSP gene expression may be involved in preventing irreversible damage or in fine tuning the recovery of mammalian cells from heat stress. PMID- 1930254 TI - Shifts in protein metabolism in some organs of freshwater fish, Cyprinus carpio under mercury stress. AB - Changes in the protein metabolism of gill, kidney and intestine of freshwater fish, Cyprinus carpio exposed to 1, 15 and 30 days to sublethal concentration (0.1 mg/l) of mercury were studied. The total, soluble and structural protein contents recorded the depletion followed by progressive increase in accumulation of free aminoacids. Concurrently, the activity of protease in the tissues was also increased. A steady enhancement in the activities of aspartate aminotransferase and alanine aminotransferase paralleled the elevation of glutamate dehydrogenase activity in the organs studied. Levels of ammonia and urea have also reported elevation. All these changes clearly documented the induction of severe proteolysis. The magnitude of these changes increased overtime. These changes were more in the gill at the initial periods of exposure (1 and 15 days), but as the period of exposure increased, these changes were more pronounced in the kidney at 30 days of exposure to sublethal concentration of mercury. PMID- 1930255 TI - Inhibition of hypoxic pulmonary vasoconstriction by diphenyleneiodonium. PMID- 1930256 TI - Mechanisms of the protective effects of transforming growth factor-beta in reperfusion injury. AB - TGF-beta appears to be an important regulatory peptide in cellular physiology. Although all of its actions are not presently known, TGF-beta functions as a cell switching molecule. In the case of ischemia-reperfusion states, TGF-beta has been shown to exert remarkably effective protective effects. These effects appear to pertain to preservation of endothelial function, particularly to maintenance of EDRF formation by the endothelium. The endothelial protection may be related to actions of TGF-beta opposing the endothelial-destabilizing actions of both TNF and superoxide radicals. However, other important mechanisms will undoubtedly be brought to light with further study of TGF-beta in these situations. PMID- 1930257 TI - Carboxylesterases in guinea pig. A comparison of the different isoenzymes with regard to inhibition by organophosphorus compounds in vivo and in vitro. AB - The different isoenzymes of carboxylesterase (CarbE) from guinea pig liver, lung and plasma were separated by gel filtration and chromatofocusing. The isoenzymes were characterized by inhibition with several different organophosphorus compounds. The bimolecular rate constants showed the same tendency of decreased inhibition for all of the isoenzymes in the order; paraoxon greater than soman greater than diisopropylphosphofluoridate (DFP) greater than bis(p nitrophenyl)phosphate. With two exceptions the inhibition constants for the different isoenzymes differed little. Subcutaneous and intraperitoneal administration of DFP and paraoxon rapidly inhibited the CarbE activity in guinea pig plasma. Much higher doses were necessary to obtain a marked inhibition in lung and liver. About 25% of CarbE activity in lung was resistant to paraoxon and DFP inhibition. Gel filtration of lung homogenate after treatment with the organophosphorus compounds showed that the CarbE activity of the medium molecular mass fractions was inhibited only weakly. This could be due to reduced accessibility to some of the lung CarbE isoenzymes. PMID- 1930258 TI - The effect of a fish oil enriched diet on oxygen toxicity and lipid peroxidation in mice. AB - Mice were fed a chow diet or diets enriched in fish oil, sunflower oil or beef tallow for 3 weeks. Fatty acid analysis was carried out in samples of plasma, brain and lungs from these animals and large changes were found in plasma and lungs with relatively small dietary-induced changes in brain tissue. Bleeding times were increased very significantly in the fish oil group, and slightly increased in the sunflower oil group. Endogenous lipid peroxidation (measured as thiobarbituric acid reactive substances) was unchanged in lung and brain, but lung tissue from fish oil fed mice produced more lipid peroxides in vitro during incubation at 37 degrees than those of other dietary groups. Mice fed the four different diets were exposed to hyperbaric oxygen at 618, 585 and 515 kPa and convulsive activity and lung damage was recorded. No dietary-induced alterations in susceptibility to oxygen toxicity were found. PMID- 1930259 TI - Heterologous expression of human microsomal epoxide hydrolase in Saccharomyces cerevisiae. Study of the valpromide-carbamazepine epoxide interaction. AB - A cDNA of human microsomal epoxide hydrolase (hmEH) was constitutively and inducibly expressed in Saccharomyces cerevisiae. The heterologous enzyme was located mainly in the microsomal fraction of yeast cells. Yeast microsomes containing hmEH exerted styrene oxide hydrolase activity (Km = 300 microM; Vmax = 22 nmol/mg min) as well as carbamazepine epoxide hydrolase activity. The hmEH catalysed exclusively the formation of carbamazepine-10,11-transdihydrodiol, since no carbamazepine-10,11-cisdihydrodiol was detected. Inhibition studies using these microsomes revealed unequivocally hmEH as the target for inhibition by the antiepileptic drug valpromide. A Ki value of 27 microM was determined for the inhibitor valpromide with styrene oxide as substrate. For carbamazepine epoxide, a Ki value of 8.6 microM was obtained, which is well in line with data published for hmEH determined with human liver microsomes. Our results demonstrate the potential of heterologous gene expression in S. cerevisiae and its application to the in vitro study of pharmacological and toxicological problems. PMID- 1930260 TI - Influence of di- and tri-phenylethylene estrogen/antiestrogen structure on the mechanisms of protein kinase C inhibition and activation as revealed by a multivariate analysis. AB - We have performed a systematic study of the interaction of 36 di- and tri phenylethylene derivatives (DPEs and TPEs) with protein kinase C (PKC). The results were submitted to a multivariate analysis in order to identify the structural features that might be implicated in interference with the activity of three PKC subspecies under three enzyme activation conditions. Four groups of test-compounds, each with common chemical features, could be distinguished clearly. The first group comprised all TPEs substituted with at least one basic dialkylaminoethoxy side-chain. These inhibited type alpha, beta and gamma PKC subspecies activated by Ca2+ and phosphatidylserine (PS) with or without diolein (DO) at micromolar concentrations but did not inhibit protamine sulfate phosphorylation. The other effectors, which all possessed a 1,1-bis-(p hydroxyphenyl) ethylene moiety, influenced PKC activity at high concentrations (30-200 microM) and could be divided into two groups. One group constituted PKC inhibitors in the TPE series and inhibited PKC activated by Ca2+, PS and DO, as well as protamine sulfate phosphorylation. The other group constituted dual-type inhibitors/activators in the DPE series and stimulated PKC in the presence of Ca2+ and low PS concentrations but inhibited the enzyme in the simultaneous presence of DO. The fourth group of compounds was inactive and had, for the most part, one or two substituents with weak steric hindrance. In agreement with previous data for six lead compounds, this study suggests that, in these chemical series, a basic amino side-chain leads to interaction with phospholipid and the regulatory domain of PKC, whereas a 1,1-bis-(p-hydroxyphenyl) ethylene moiety leads to interaction with the catalytic domain of the enzyme. PMID- 1930261 TI - Thiol-group reactivity, hydrophilicity and stability of alloxan, its reduction products and its N-methyl derivatives and a comparison with ninhydrin. AB - The diabetogenic agent, alloxan, is a hydrophilic and chemically unstable compound. The logarithm of the octanol/water partition coefficient of alloxan was found to be -1.86; its half-life at pH 7.4 and 37 degrees in phosphate buffer was 1.5 min. The partition coefficients and half-lives of the alloxan reduction products, alloxantin and dialuric acid, were very similar to those of the parent compound; N-methylalloxan and N,N'-dimethylalloxan were less hydrophilic but more unstable. Ninhydrin was found also to be hydrophilic although this compound, in contrast to alloxan and its derivatives, was quite stable in aqueous solution. Alloxan and its N-methyl derivatives were reduced by thiols and in the presence of glutathione and cysteine, rapid redox cycling occurred, with formation of 'active oxygen' species; no such reaction was observed, however, with ninhydrin. Comparatively slow redox cycling was recorded with alloxan derivatives and dithiothreitol although rapid cycling occurred with ninhydrin and this dithiol. Such differences may explain why ninhydrin does not share with alloxan a selective toxic effect upon the pancreatic B-cell. PMID- 1930262 TI - Interaction of cis-diamminedichloroplatinum (II) with single-stranded DNA in the presence or absence of Escherichia coli single-stranded binding protein. AB - We have compared the mode of fixation in vitro of the antitumor drug cis diamminedichloroplatinum (II) (cis-DDP) to single-stranded M13mp10 DNA either in the presence or absence of the Escherichia coli single-stranded binding protein (SSB). Platinum binding sites have been identified by taking advantage of their capacity to inhibit DNA replication of primed M13 DNA catalysed by E. coli DNA polymerase I large fragment. We report here that the presence of SSB increases the number of platinum-DNA lesions and alters their distribution. We also present evidence that SSB allows cis-DDP to bind to DNA sequences otherwise less accessible. PMID- 1930263 TI - Evidence that polymyxin B is a glucose transport inhibitor. AB - The effect of polymyxin B on 3-O-methylglucose transport was studied in isolated rat adipocytes and erythrocytes. Polymyxin B (300 micrograms/mL) inhibited basal transport and insulin-stimulated transport of 3-O-methylglucose in adipocytes by 26.1 and 40.1%, respectively. Polymyxin B at concentrations of 300 and 3000 micrograms/mL inhibited transport of 3-O-methylglucose in erythrocytes by 20.0 and 40.8%, respectively. Polymyxin E at a concentration of 3000 micrograms/mL also inhibited, by 40.6%, the transport of 3-O-methylglucose in erythrocytes but 300 micrograms/mL of polymyxin E did not inhibit it significantly. These results indicate that polymyxin B inhibits glucose transport per se, as well as the insulin-dependent stimulation of glucose transport. PMID- 1930264 TI - The flavin-containing monooxygenase of mouse kidney. A comparison with the liver enzyme. AB - Flavin-containing monooxygenase (FMO; EC 1.14.13.8) was purified from mouse kidney microsomes and compared to that isolated from mouse liver microsomes. The purified enzymes from kidney and liver appeared as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 58,000 daltons. On wide range (pH 3.5 to 9.0) isoelectric focusing, FMOs from kidney and liver resolved as a single band with an isoelectric point of 8.2. The enzymes from both kidney and liver have a pH optimum of 9.2. Thiobenzamide-S-oxidation catalyzed by both enzymes was sensitive to inhibition by the competitive inhibitors thiourea and methimazole. At an n-octylamine concentration of 3 mM, thiobenzamide-S-oxidation by the kidney FMO was increased by 122% and that by the liver FMO by 148%. Km and Vmax values were determined and compared between the two tissue enzymes for xenobiotic substrates containing nucleophilic nitrogen, sulfur or phosphorus atoms. In general, for most FMO substrates, Km and Vmax values were similar between kidney and liver FMO with only a few exceptions. The Km and Vmax values for fenthion for kidney were only half of those observed for liver FMO. Fonofos was unusual in having a low Km as well as a low Vmax for both tissue enzymes. Anti-sera developed to the FMO purified from kidney and liver showed cross-reactivity with each purified enzyme as well as with a protein with the same molecular weight as the purified FMO present in both kidney and liver microsomes. These bands showed equal intensity based on an equivalent amount of protein. Analysis of kidney and liver FMO by proteolytic digestion followed by visualization of peptides by silver staining or immunoblotting showed only minor differences between the enzymes of the two tissues. The amino acid composition of both mouse kidney and liver FMO was low in methionine and histidine and rich in aspartate/asparagine, glutamate/glutamine, leucine, valine and glycine. Edman degradation of the purified mouse kidney and liver FMO provided a single amino acid sequence of the NH2-terminus. This sequence matched exactly with the cDNA-deduced sequence reported for the pig and rabbit liver beginning with the fifth amino acid and contained the highly conserved FAD-binding domain Gly-X-Gly-X-X-Gly, commonly found in a number of other FAD-binding proteins. These studies indicate that the renal and hepatic forms of FMO from mouse are similar enzymes that are immunologically related and show only a few minor differences. PMID- 1930265 TI - In vivo covalent binding of clofibric acid to human plasma proteins and rat liver proteins. AB - Recent studies have shown that acyl-glucuronide conjugates are chemically reactive electrophilic metabolites that can undergo transacylation reactions resulting in intra-molecular rearrangement, hydrolysis and covalent binding of aglycone to albumin both in vitro and in vivo. The hypolipidaemic agent clofibrate is eliminated almost entirely as clofibric acid glucuronide in humans and rats. The formation of clofibric acid-protein adducts was investigated in 14 patients receiving 0.5-2.0 g/day of clofibrate for hypercholesterolaemia, and in liver homogenates from 20 rats administered 280 mg/kg/day of clofibric acid for up to 21 days. Total clofibric acid concentrations in the patients ranged from 0 to 114 mg/L. Covalently bound clofibric acid-protein adducts were detected in all patients, even in one subject in whom there was no measurable plasma clofibric acid. Concentrations ranged from 2.2 to 53.4 ng/mg protein and, in eight patients receiving 1.0 g/day of clofibrate, were correlated (P less than 0.05) with renal function as assessed by creatinine clearance. Clofibric acid-protein adducts were also present in rat liver homogenates, and increased with increasing duration of treatment (P less than 0.0001), from a mean (SE) of 10.1 (0.7) to 32.3 (1.6) ng/mg protein. The covalent binding of drugs to tissue macromolecules has traditionally been associated with toxicity. Further research is required to elucidate the role of acyl-glucuronide conjugates in the formation of drug protein adducts and their biological consequences. PMID- 1930266 TI - The role of protein kinase C and the phosphatidylinositol cycle in multidrug resistance in human ovarian cancer cells. AB - The present study aimed to investigate the role of protein kinase C (PKC), the phosphatidylinositol pathway (PI) and cytosolic calcium in multidrug resistance (MDR) in human ovarian carcinoma cells. Binding of the phorbol ester 13,14 dibutyrate (PDBu) was 3-fold higher in resistant A2780AD versus sensitive A2780 cells indicating increased PKC activity. However, when inositol phosphate production (IP) was measured in quiescent cells similar total IP release was seen in both lines suggesting no difference in the basal turnover of PI. Non-specific stimulation of the PI pathway was achieved with the calcium ionophore A23187 which increased IP production in a time- and dose-dependent fashion in both cell lines but was significantly less effective in A2780AD. The PI pathway was investigated further using the agonists aluminium fluoride, serum and bombesin but these agents failed to elicit a response. The effect of a wide range of Adriamycin concentrations on the PI cycle and cell growth was also studied. Intracellular calcium was measured with the fluorescent dye fura-2 pentaacetoxymethylester (Fura-2). A23187 produced a rise in cytosolic calcium in A2780 and A2780AD but from a level 3-fold lower in the unstimulated resistant cell line. The dose responsiveness of this effect was greater but irreversible in A2780AD cells. Collectively these results imply that alterations in PI turnover appear not to be responsible for the differences in PDBu binding and calcium handling observed between A2780 and A2780AD and suggests only a minor role for the PI cycle in the maintenance of MDR in human ovarian cancer cell lines. PMID- 1930267 TI - Biochemical and pharmacological interactions between nitroglycerin and thiols. Effects of thiol structure on nitric oxide generation and tolerance reversal. AB - Co-administration of N-acetylcysteine (NAC) with nitroglycerin (NTG) has been shown to partially reverse nitrate tolerance and to potentiate the hypotensive effect of NTG in humans. However, a high clinical dose of NAC was required for this pharmacologic interaction resulting in the production of unwanted side effects. Therefore, sulfhydryl compounds more active than NAC need to be identified if this interaction is to be exploited clinically. We previously suggested that the effect of sulfhydryl compounds on NTG may be mediated by the formation of S-nitrosothiol or nitric oxide (NO) extracellularly to the vascular smooth muscle cell (e.g. in plasma) (Fung et al., J. Pharmacol Exp Ther 245: 524 530, 1988). In an attempt to understand the structural features which govern this thiol-catalyzed NO generation from NTG, nineteen different aliphatic and ten aromatic sulfhydryl compounds were examined with respect to their catalytic activity to generate NO from NTG in plasma. Significantly enhanced production of NO was observed with most sulfhydryl compounds examined when compared to buffer control. Among the aliphatic thiols, only mercaptosuccinic acid was more potent than NAC (2x), whereas among the aromatic thiols, both thiosalicylic acid (TSA, 10x) and TSA-methyl ester (3x) were more potent than NAC. Comparative in vitro relaxation studies were carried out using isolated (and nitrate-tolerant) rat aortic rings with NTG/TSA and NTG/NAC, in the presence of 0.5% (v/v) plasma. Under these conditions, partial reversal of NTG tolerance could be achieved with TSA, but not with NAC. These data are consistent with the view that extracellular production of NO or S-nitrosothiol serves as a tolerance-reversing mechanism of thiols on NTG. TSA appears to be a more potent sulfhydryl compound than NAC in this biochemical and pharmacologic interaction. PMID- 1930268 TI - Influence of ellagic acid on antioxidant defense system and lipid peroxidation in mice. AB - Addition of ellagic acid (EA) to liver microsomes of mice resulted in a steady increase in inhibition of NADPH-dependent lipid peroxidation up to 2 mM concentration. The maximum of 70% inhibition of ascorbate-dependent lipid peroxidation was achieved at 1 mM concentration of EA. Feeding of EA significantly increased the levels of reduced glutathione and glutathione reductase in liver and lungs of male and female mice. However, there were no changes in the activities of catalase and superoxide dismutase. On the other hand, microsomes from liver and lungs of EA fed animals showed significantly suppressed NADPH- and ascorbate-dependent lipid peroxidation. PMID- 1930269 TI - Involvement of tryptophan residue(s) in the specific binding of agonists/antagonists to 5-HT3 receptors in NG108-15 clonal cells. AB - Chemical modification of the 5-HT3 receptors in membranes from NG108-15 hybridoma cells was achieved using protein modifying reagents specific for various amino acid residues: N-bromosuccinimide for tryptophan, dithiothreitol for cystine, sodium tetrathionate for cysteine, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline for aspartic and glutamic acids, diethylpyrocarbonate for histidine, tetranitromethane for tyrosine and 2,3 butanedione for arginine. Among all the reagents tested, N-bromosuccinimide produced the largest alteration in the specific binding of [3H]zacopride onto 5 HT3 receptors. A significant reduction in Bmax (approximately 50%) with no change in Kd were noted on [3H]zacopride specific binding to membranes which were incubated with 40 microM N-bromosuccinimide for 60 min at 25 degrees. The occupancy of 5-HT3 receptor binding sites by various 5-HT3 agonists and antagonists (phenylbiguanide, ondansetron, granisetron, MDL 72222) prevented, at least partially, any subsequent reduction in [3H]zacopride specific binding by N bromosuccinimide treatment. However, neither m-chloro-phenylbiguanide, among the agonists, nor zacopride, among the antagonists, were able to prevent the effect of N-bromosuccinimide, suggesting that variations might exist in the molecular mechanisms implicated in the binding of 5-HT3 ligands to the recognition site on 5-HT3 receptors. Nevertheless, these data support the suggestion that tryptophan residue(s) are probably involved in the binding of agonists and antagonists onto 5-HT3 receptors in NG108-15 cell membranes. PMID- 1930270 TI - Effects of diisopropyl phosphofluoridate, sarin and soman on the accessibility of proteins, in the electroplax membrane, to lactoperoxidase-catalyzed iodination. AB - Anticholinesterases (anti-ChE) have some effects on biological properties including behavior, vision, and electroencephalograms, which are often long lasting and which do not appear to be due to cholinesterase (ChE; EC 3.1.1.7) inhibition, but which may be due to alterations in the organization and/or functioning of the cellular membrane. We assessed the effects of anti-ChE agents on the asymmetric organization of proteins in the innervated (excitable) and in the non-innervated (non-excitable) plasma membrane of the electroplax from the electric eel. Lactoperoxidase-catalyzed iodination (LCI) was carried out under impenetrable conditions in intact electroplax (where protein exposure on the external surface is monitored) and in split electroplax (where total protein labeling on both the external and internal monolayers of the plasma membrane bilayer is monitored). Labeling in split electroplax was much greater than in intact electroplax for all molecular weight groupings of proteins (30,000 to greater than 200,000). The anti-ChE agents diisopropyl phosphofluoridate (DFP; 10(-3) M), sarin (10(-4) M) and soman (10(-4) M, 10(-6) M, 2.5 x 10(-9) M) did not alter permeability, protein content or the electrophoretic pattern of the plasma membrane proteins of the electroplax. DFP, sarin and 10(-6) M soman (but not 2.5 x 10(-9) M or 10(-4) M soman) increased labeling of some of the molecular weight fractions in the non-innervated plasma membrane as monitored by LCI in intact electroplax. Under these same conditions, DFP and 10(-4) M soman increased labeling in the innervated plasma membrane while 10(-6) M soman decreased labeling. When LCI was carried out in split electroplax, 10(-4) M soman caused a decrease in labeling in both the innervated and non-innervated plasma membrane indicating a decrease of exposed proteins on the cytoplasmic surface of the plasma membrane. These concentrations of the anti-ChE agents caused almost complete ChE inhibition in the electroplax cells, except for 2.5 x 10(-9) M soman which caused little or no inhibition. These results suggest that alterations in protein asymmetry, as monitored by LCI of accessible proteins, are not directly due to ChE inhibition. These changes in organization of membrane proteins could contribute to a variety of effects of anti-ChE agents which are not due to ChE inhibition. PMID- 1930271 TI - Modulation of 3'-azido-3'-deoxythymidine catabolism by probenecid and acetaminophen in freshly isolated rat hepatocytes. AB - Metabolic studies of 3'-azido-3'-deoxythymidine (AZT) in humans have demonstrated that this compound is primarily eliminated as a 5'-O-glucuronide, 3'-azido-3' deoxy-5'-beta-D-glucopyranuronosylthymidine (GAZT), accounting for approximately 80% of the administered dose. Recently, we characterized the complete catabolic pathway of AZT in freshly isolated rat hepatocytes in suspension, demonstrating extensive formation of three catabolites, including GAZT, 3'-amino-3' deoxythymidine (AMT), and 3'-amino-3'-deoxy-5'-beta-D-glucopyranuronosylthymidine (GAMT). The present study evaluated the effects of probenecid (PROB) and acetaminophen (ACET), two agents which are also metabolized by UDP glucuronyltransferase, on the metabolism and transmembrane distribution of AZT in rat hepatocytes. Pre-exposure of cells to 350 microM PROB 30 min prior to the addition of 10 microM [3H]AZT decreased intracellular GAZT levels by approximately 10-fold. Interestingly, AMT formation was enhanced approximately 1.5-fold in the presence of PROB, probably resulting from increased AZT availability. In contract, pre-exposure to 50 microM ACET 30 min prior to addition of 10 microM [3H]AZT did not substantially alter AZT glucuronidation. Additionally, decreased AZT catabolism by PROB did not contribute to the formation of 5'-phosphorylated derivatives of AZT. Agents which undergo glucuronidation may thus not necessarily affect AZT conversion to GAZT, and their potential interactions should be investigated using in vitro systems prior to co administration with AZT. PMID- 1930272 TI - The correlation of the oxidation potentials of structurally related dibenzo[1,4]dichalcogenines to their antioxidance capacity in biological systems undergoing free radical-induced lipid peroxidation. AB - A series of structurally related dibenzo[1,4]dichalcogenines possessing similar lipid solubilities but greatly differing oxidation potentials were tested for their ability to inhibit stimulated lipid peroxidation in ADP/Fe2+/ascorbate treated liver microsomes and in hepatocytes treated with either t butylhydroperoxide or diquat. In general, there was a close correlation between the half-wave oxidation potential of a particular compound and its antioxidant activity in the microsome and cell systems, with compounds possessing the lowest potential being the most potent antioxidants and vice versa. The Te/O and Te/S and S/O-substituted compounds, with oxidation potentials between 0.65 and 0.87 V, demonstrated most potent activity. Above this potential the antioxidant activity of the structure declined rapidly. The Te/O and Te/S compounds are among the most potent synthetic antioxidants described possessing IC50 values in the microsome system lower than 0.5 microM. This study clarifies the critical role of redox potential of an antioxidant site on a particular molecule without the complication of variable lipid solubility and may allow the definition of an optimal potential for antioxidant activity in biological systems. PMID- 1930273 TI - Effect of the peroxisome proliferator LY171883 on triglyceride accumulation in rats fed a fat-free diet. AB - LY171883 is a leukotriene D4 antagonist that induces peroxisome proliferation in the rodent liver. Like many peroxisome-proliferating agents, it causes transient lipid accumulation and several other changes in hepatic lipid metabolism. The effect of LY171883 on lipid metabolism was studied further in rats maintained on a fat-free diet. Administration of a fat-free diet for 14 days caused a 5.6-fold increase in liver triglycerides associated with a 3.3-fold increase in fatty acid synthetase. Co-administration of 0.1% LY171883 increased liver triglycerides slightly, whereas 0.3% LY171883 prevented the accumulation of triglycerides. Furthermore, treatment with 0.3% LY171883 reversed the fatty liver in rats pretreated with the fat-free diet for 14 days. Fatty acid synthetase activity increased comparably in all treatment groups, indicating that 0.3% LY171883 did not prevent the lipogenic response to a fat-free diet. In rats treated with 0.3% LY171883, peroxisomal beta-oxidation increased 9.5-fold, mitochondrial beta oxidation 4.8-fold, carnitine palmitoyltransferase I 1.9-fold, and plasma ketones 3-fold. In the 0.1% dose group the increases in these parameters were smaller. The data indicate that 0.3% LY171883 sufficiently increased mitochondrial and peroxisomal beta-oxidation such that fatty acids generated by lipogenesis were preferentially oxidized rather than esterified to triglycerides. In the 0.1% dose group oxidation was only mildly increased, and the excess fatty acids continued to be esterified. PMID- 1930274 TI - Changes in plasma lipoprotein metabolism in chicks in response to polychlorinated biphenyls (PCBs). AB - The results of the present study strongly suggest that the hypertriglyceridaemia in chicks treated with Aroclor 1254 is a result of reduction in VLDL clearance rather than an increase in rate of VLDL secretion. The decrease in post-heparin LPL activity responsible for reduced VLDL clearance may be mediated by cytokines produced by chronic activation of the immune system. PMID- 1930275 TI - P2-purinoceptors in a renal epithelial cell line (LLC-PK1). PMID- 1930276 TI - Glucuronidation of imipramine in rabbit and human liver microsomes: assay conditions and interaction with other tertiary amine drugs. AB - The present work confirms that rabbit liver microsomes afford a good in vitro model for studying the glucuronidation of drugs containing tertiary amino groups. Furthermore, the availability of the assay procedure described above will allow us to understand further the basis for the inter-species differences in the metabolism of tertiary amines, and will eventually aid in our identification of the UDPGT isozyme(s) responsible for the conjugation of these compounds in man. PMID- 1930277 TI - Sulfation and hemolytic activity of cyclodextrin. PMID- 1930278 TI - Enzymatic conjugation of chlorambucil with glutathione by human glutathione S transferases and inhibition by ethacrynic acid. PMID- 1930279 TI - Effect of cimetidine on the metabolism of coumarin by rat, gerbil and human liver microsomes. PMID- 1930280 TI - The role of specific cytochromes P450 in the formation of 7,12 dimethylbenz(a)anthracene-protein adducts in rat liver microsomes in vitro. AB - The role of specific cytochrome P450 (P450) isoforms in the formation of adducts of 7,12-dimethylbenz(a)anthracene metabolites and membrane proteins has been investigated in vitro with microsomal fractions prepared from rats pretreated with various isoenzyme selective inducers. The effects of isoenzyme selective inhibitors were also evaluated. Adduct formation was shown to be mediated by P450 catalysed reactions but was unaltered, relative to untreated animals, in membranes from pyrazole- and clofibrate-treated animals suggesting that CYP2E1 and CYP4A1 are not involved in this process. However, adduct formation was significantly increased in microsomes from Sudan III-, phenobarbital- and dexamethasone-treated rats, suggesting the involvement of the CYP1A, CYP2B and CYP3A subfamilies, respectively. These conclusions were further supported by the finding that adduct formation in these microsomes could be inhibited by the isoenzyme-selective inhibitors alpha-naphthoflavone, metyrapone and troleandomycin, respectively. PMID- 1930281 TI - Histamine-stimulated increases in intracellular calcium in the smooth muscle cell line, DDT1MF-2. AB - Suspensions of undifferentiated cultured vas deferens smooth muscle cells (DDT1MF 2) were loaded with the calcium-sensitive fluorescent dye fura-2. Exposure to histamine elicited a rapid and maintained increase in intracellular free calcium ([Ca2+] i) with an EC50 of 1.3 +/- 0.7 x 10(-5) M. The initial rise is a consequence of calcium release from intracellular stores, whereas the maintained or plateau phase, which is dependent upon the presence of extracellular calcium, is associated with calcium influx. Experiments in nominally Ca(2+)-free buffer attenuated the initial rise in [Ca2+]i (i.e. peak height) and virtually abolished the plateau phase. Re-addition of 2 mM Ca2+ (during experiments performed in nominally Ca(2+)-free buffer) resulted in a return of the plateau phase. Pretreatment with the H1-antagonist mepyramine (100 nM; Kd = 1.0 +/- 0.4 nM, N = 3) completely blocks the response to histamine, whereas tiotidine (2 microM; H2 antagonist) had no effect. In conclusion, the present data would suggest that functional H1-receptors found in hamster vas deferens smooth muscle cells are typical of the "classical" H1-receptor in both its control of intracellular Ca2+ and sensitivity to antagonism by mepyramine. PMID- 1930282 TI - Mechanistic aspects of the oxidation of phenothiazine derivatives by methemoglobin in the presence of hydrogen peroxide. AB - Mechanistic aspects of the reaction of hydrogen peroxide with methemoglobin with respect to phenothiazine oxidation have been studied. Three phenothiazines, methoxy- (MoPZ), chlor- (CPZ) and methoxycarbonylpromazine (MaPZ), have been used. These phenothiazines differ only in substitution at the 2-position, which contributes substantially to the electron-donating properties of these compounds. Reaction with hydrogen peroxide oxidizes methemoglobin to ferrylhemoglobin, which contains iron(IV)-oxo porphyrin moiety and a protein radical. The phenothiazines are oxidized by ferrylhemoglobin in the presence of H2O2 mainly to their sulfoxides, with a radical cation as intermediate. The conversion rates (MoPZ greater than CPZ greater than MaPZ) decrease with the electron-withdrawing ability of the 2-substituent, as indicated by Hammett sigma para values. Hydrogen peroxide consumption during the reaction is similar for the three phenothiazines. Denaturation reactions that occur upon exposure of methemoglobin to hydrogen peroxide have been investigated. For this heme-protein cross-linking was studied by means of heme retention by the protein after methyl ethyl ketone extraction. Furthermore, oxygen consumption during the reaction was assayed, which indicates formation of protein-peroxy radicals. The extent of both heme-protein cross linking and oxygen consumption is decreased by phenothiazines in the same order as the phenothiazine conversion rate. CPZ sulfoxide is not converted by methemoglobin in the presence of hydrogen peroxide, and CPZ sulfoxide shows no effect on heme-protein cross-linking and oxygen consumption. The results are explained by electron transfer from phenothiazine to the protein radical. Stronger electron donors (MoPZ greater than CPZ greater than MaPZ) are converted faster and by reducing the protein radical they better protect hemoglobin against denaturation. A catalytic cycle, that takes into account our observation and the existing knowledge of hemoglobin oxidation states, is presented. PMID- 1930283 TI - The effect of vindesine on methotrexate hydroxylation in the rat. AB - The effect of vindesine (VDS) on methotrexate (MTX) disposition was studied in bile-drained rats administered VDS prior to [3H]MTX, and in isolated rat hepatocytes and rat liver homogenate concomitantly incubated with MTX and VDS at 37 degrees. In vivo, 7-hydroxylation was reduced by 0.65 mg/kg VDS. In VDS treated animals, biliary recovery of the MTX dose (50 mg/kg) as 7 hydroxymethotrexate (7-OH-MTX) (1.75 +/- 0.2%, mean +/- SEM) was significantly reduced compared to controls (2.83 +/- 0.57%). In vitro, hydroxylation of MTX (10 200 microM) in hepatocytes was reduced by 14.3 and 66.4% (means) at 12.5 and 100 microM VDS, respectively. With increasing VDS concentrations up to 100 microM, a reduction in intracellular MTX accumulation could account for the decreased MTX hydroxylation. Experiments in a cell free system gave no evidence of inhibition of 7-OH-MTX formation by VDS. In vitro MTX transport studies demonstrated that VDS inhibited the hepatocellular influx of MTX, as (1) the accumulation of MTX corresponded inversely to increasing VDS concentrations and (2) the MTX efflux was not increased by VDS. The apparent Ki for VDS inhibition of MTX influx was 57 microM. We suggest that VDS, by reducing the 7-OH-MTX formation in liver cells, may have implications for combination chemotherapy regimens which include MTX. PMID- 1930284 TI - Inhibitor studies of purified haemopoietic (myeloid) cell esterases. Evidence for the existence of distinct enzyme species. AB - Human myeloid cells synthesize and express two major species of esterase, defined by isoelectric focusing (IEF). The first of these (MonEst) is specifically associated with haemopoietic cells of monocytic lineage, whereas the other species (ComEst) is common to all myeloid cells (granulocytes and monocytes) irrespective of lineage affiliation. Having recently purified these two species of human myeloid cell esterase, this present study extensively investigated the effects of 17 different inhibitors on their ability to hydrolyse the synthetic substrate alpha-naphthyl acetate (alpha NA). Significant inhibition of both ComEst and MonEst was exerted by 1% sodium dodecyl sulphate (SDS) and 1.0 mM diethyl pyrocarbonate (DEPC), but the patterns of inhibition for the two esterase species with the remaining compounds studied differed considerably; for example, 0.2 mM phenylmethylsulphonyl fluoride (PMSF), 5.0 x 10(-3) M dichloroisocoumarin (DCIC) and 0.1 mM N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) all inhibited MonEst but not ComEst. Mechanisms of inhibition were also examined and these studies established that SDS, PMSF, DCIC and TPCK irreversibly inactivated MonEst whilst the inhibition of ComEst by SDS was reversible. Analysis of inhibition kinetics further showed that (a) the reversible inhibition of both ComEst and MonEst by sodium fluoride (NaF) was noncompetitive (with Ki values of 1.28 and 0.01 mM, respectively, indicating a marked difference in sensitivity); (b) the inhibition of MonEst by PMSF was of 'mixed' noncompetitive-competitive type; and (c) that DEPC exerted noncompetitive inhibition with similar Ki values (0.05 mM) for both esterase species. These observations unequivocably demonstrate that ComEst and MonEst are unrelated enzyme species, with a common ability to hydrolyse alpha NA, and that these esterase show marked differences with respect to their active sites as adjudged by inhibitor sensitivities. These observations are particularly relevant to the histochemical analysis of these enzymes and to the elucidation of their in vivo functions. PMID- 1930285 TI - Relationship of membrane fluidity, chemoprotection, and the intrinsic toxicity of butylated hydroxytoluene. AB - In isolated rat hepatocytes, many chemicals elicit toxicity which is inhibitable by antioxidants such as butylated hydroxytoluene (BHT). Although BHT protection is evident at concentrations of less than about 50 nmol/mg protein, higher concentrations exhibit intrinsic concentration-dependent toxicity, which involves mitochondrial dysfunction. We evaluated the possibility that both chemoprotection and intrinsic toxicity could be explained by a common mechanism involving alterations in the physical properties of cellular membranes. In the red blood cell (RBC) osmotic fragility assay, BHT at less than 60 nmol/mg protein protected against osmotic fragility; however, BHT at higher concentrations enhanced osmotic fragility such that total osmolysis occurred at 135 nmol/mg. The BHT-mediated alterations in osmotic fragility correlated with changes in membrane fluidity, determined by fluorescence polarization of the hydrophobic probe 1,6-diphenyl 1,3,5-hexatriene. Protection from osmolysis correlated with decreased fluidity, while enhanced RBC fragility correlated with increased fluidity. In rat hepatocyte suspensions, high BHT concentrations also permeabilized the plasma and mitochondrial membranes to enzyme leakage, and these effects were accompanied by enhanced membrane fluidity. Although other mechanisms may be operative, alterations in membrane fluidity appear to be, in part, responsible for the observed chemoprotective effects at low concentrations, and intrinsic toxicity at higher concentrations of BHT. PMID- 1930286 TI - DNA base damage by beta-lactam, tetracycline, bacitracin and rifamycin antibacterial antibiotics. AB - Several antibacterial antibiotics have been shown to participate with transition metal ions in chemical reactions leading to the formation of reactive oxygen species. An important host defence mechanism for dealing with invading bacteria involves the production of reactive oxygen species, such as superoxide, hydrogen peroxide and hypochlorous acid, by phagocytic cells. The production of reactive oxygens by redox cycling antibacterial antibiotics has led us to suggest that a 'phagomimetic' contribution may also be made in vivo. Here we show that four structurally different antibacterial antibiotics, in the presence of added copper salt, bring about oxidative modification to bases in DNA detected using gas chromatography-mass spectrometry. The drug most damaging to DNA was rifamycin SV which was more active than a reference mixture of hydrogen peroxide and ascorbic acid. PMID- 1930287 TI - Structural features of dermatan sulfates and their relationship to anticoagulant and antithrombotic activities. AB - Dermatan sulfate is a polydisperse, microheterogeneous sufated copolymer of N acetyl-D-galactopyranose and idopyranosyluronic acid that is currently under clinical investigation as a new antithrombotic agent. The structure and activity of two pairs of dermatan sulfates, isolated from bovine and porcine mucosa, were studied. One dermatan sulfate from each species demonstrated high in vivo antithrombotic activity in the rat vena cava assay. The in vitro anticoagulant activity of each dermatan sulfate was determined using activated partial thromboplastin time (APTT), thrombin time (TT) (5 units), calcium thrombin time (CaTT) (5 units), Heptest, anti-factor Xa and anti-factor IIa antithrombin assays and heparin cofactor II amidolytic assays. The coagulation-based assays gave the best correlation to in vivo antithrombotic activity. The physical and chemical properties of each dermatan sulfate were determined using 1H-NMR and 13C-NMR spectroscopy, molecular weight determination, potentiometric titration, chemical degradative analysis, chondroitin lyase degradative analysis and oligosaccharide mapping. These analyses indicated that the major difference between dermatan sulfates from a particular species having high and low in vivo antithrombotic activity was their iduronic acid content. The relation between increased iduronic acid content and increased in vivo antithrombotic activity may be the result of the conformational flexibility of this residue. PMID- 1930289 TI - Possible mechanism of action of desferrioxamine and 2,2'-bipyridyl on inhibiting the in vitro growth of Plasmodium falciparum (FCR 3 strain). PMID- 1930288 TI - Two-step inactivation of bee venom phospholipase A2 by scalaradial. AB - Scalaradial (SLD), a marine natural product isolated from the sponge (Cacospongia sp., possesses anti-inflammatory properties in vivo and in vitro (Pharmacologist 32: 168, 1990). In this study we characterize its effects against bee venom phospholipase A2 (PLA2; EC 3.1.1.4). SLD is a potent inactivator of bee venom PLA2 with an IC50 value of 0.07 microM. Inactivation of bee venom PLA2 occurred in a time-dependent, irreversible manner. The rate of inactivation followed first order reaction kinetics and was dependent on the concentration of SLD. Kinetic analysis suggested a two-step mechanism of inactivation: an initial apparent noncovalent binding (Ki = 4.5 x 10(-5) M) followed by covalent modification. The rate of inactivation was reduced markedly in the presence of excess phosphatidylcholine, suggesting that modification of the enzyme occurs at or near the substrate binding site. PMID- 1930290 TI - Effects of glimepiride and glibenclamide on insulin and glucagon secretion by the perfused rat pancreas. AB - Glimepiride and glibenclamide act apparently in a closely comparable manner upon both insulin and glucagon release. Except for the decreased efficiency of D glucose in suppressing glucagon release after a prior exposure of the pancreas to the hypoglycemic sulfonylureas, no evidence was obtained to suggest that a positive glucagonotropic action of the latter drugs would counteract their hypoglycemic action, as mainly attributable to stimulation of insulin release. PMID- 1930291 TI - Organic aciduria in fasted rats caused by 2-[6-(4-chlorophenoxy)hexyl]oxirane-2 carboxylate (etomoxir). PMID- 1930292 TI - Pharmacology and second messenger interactions of cloned muscarinic receptors. PMID- 1930293 TI - Renal and hepatic microsomal enzymes responsible for bioactivation of 3-methoxy-4 aminoazobenzene in the rodent. AB - Activities of the renal and hepatic microsomal enzymes responsible for the N hydroxylation and mutagenic activation of 3-methoxy-4-aminoazobenzene (3-MeO-AAB) were examined in male mice, rats, hamsters and guinea pigs. In all these rodent species, hepatic microsomes showed definite N-hydroxylation of 3-MeO-AAB, whereas the renal activity was detected only in mice. The hepatic enzyme responsible for N-hydroxylation of 3-MeO-AAB (3-MeO-AAB N-hydroxylase) was induced in all species except mice by phenobarbital and selectively in mice and hamsters by 3 methylcholanthrene, whereas these cytochrome P450 inducers did not affect the renal enzyme in mice, rats or hamsters. In individual microsome samples, activities for N-hydroxylation and mutagenic activation of 3-MeO-AAB correlated well. These results indicate that the renal and hepatic enzymes responsible for the metabolic activation of 3-MeO-AAB differed among different species of rodent animals in terms of their activity and inducibility with cytochrome P450 inducers. PMID- 1930294 TI - Bioactivation of CB 1954: reaction of the active 4-hydroxylamino derivative with thioesters to form the ultimate DNA-DNA interstrand crosslinking species. AB - 5-(Aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide is the active form of CB 1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide). This hydroxylamine is formed by the bioreduction of CB 1954 by the enzyme DT diaphorase and accounts for the highly selective cytotoxicity of this compound. The reason why the hydroxylamine derivative is so cytotoxic is that, in contrast to CB 1954, it can react difunctionally as characterized by the formation of DNA-DNA interstrand crosslinks in cells treated by this agent. However, although the 4-hydroxylamine compound can produce these crosslinks in cells it cannot crosslink naked DNA (Knox et al., Biochem Pharmacol 37: 4661-4669, 1988). We show here that 5 (aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide can become a species capable of binding to DNA and producing interstrand crosslinks, by a direct, non-enzymatic reaction with either acetyl coenzyme A, butyl and propyl coenzyme A or S acetylthiocholine. Coenzyme A itself cannot produce these effects. The major product of the reaction between the 4-hydroxylamine and thioesters was identified as 4-amino-5-(aziridin-1-yl)-2-nitrobenzamide. However, this compound is not capable of producing the above effects and the major DNA reactive species was a minor product of the reaction. It is proposed that the ultimate, DNA reactive, derivative of CB 1954 is 4-(N-acetoxy)-5-(aziridin-1-yl)-2-nitrobenzamide. PMID- 1930295 TI - Reduced ouabain-sensitive potassium entry as a possible mechanism of multidrug resistance in P388 cells. AB - Multidrug-resistant P388 cells were found to be resistant also to a variety of ammonium, phosphonium and arsonium compounds. As previously shown for anthracyclines and vinca alkaloids, the resistance to the permanently charged lipophilic cationic compounds could be circumvented by verapamil. Relative to drug-sensitive cells, K+ uptake and plasma membrane Mg-ATPase activity in multidrug-resistant cells are ouabain resistant. The intracellular K+ concentration in drug-resistant cells is maintained at a normal level by increased activity of the furosemide sensitive transport system. It is suggested that the reduced activity of the electrogenic Na(+)-K+ pump in multidrug resistant, cells could result in a lower transmembrane potential and therefore reduced accumulation of cationic lipophilic compounds. PMID- 1930296 TI - The repair of DNA damage induced in V79 mammalian cells by the nitroimidazole aziridine, RSU-1069. Implications for radiosensitization. AB - The induction and repair of single (ssb) and double (dsb) strand breaks in DNA under aerobic or hypoxic conditions have been determined using sucrose sedimentation techniques following incubation of V79 mammalian cells with RSU 1069 or misonidazole, representative of a conventional 2-nitroimidazole radiosensitizer, for 1-1.5 hr at either 293 or 277 degrees K and subsequent irradiation at 277 degrees K. In all cases, the dose dependences for the induction of strand breaks are linear and consistent with an enhancement in the yield of DNA damage induced by the 2-nitroimidazoles under hypoxic conditions. With RSU-1069 at 293 degrees K, the dose dependence of ssb is displaced reflecting DNA damage induced during pre-incubation. From these dependences, it is evident that the enhanced radiosensitization by RSU-1069 may not be accounted for in terms of accumulation of the agent at DNA. From the repair studies, DNA breaks induced by RSU-1069 in the absence of radiation have been shown to persist for at least 3 hr. With a combination of RSU-1069 and radiation under hypoxic conditions, the repair timescale of the induced breaks is significantly longer and an increase in the residual yields of both ssb and dsb (at 2-3 hr) was observed when compared with the observation in the presence of misonidazole or oxygen. From these studies, it is inferred that the enhanced radiosensitization of RSU-1069 at 293 degrees K is a consequence of the formation of non-repairable DNA damage together with a modification of the repairability of the radiation induced DNA breaks. PMID- 1930297 TI - Differences between human, rat and guinea pig hepatocyte cultures. A comparative study of their rates of beta-oxidation and esterification of palmitate and their sensitivity to R-etomoxir. AB - Rat hepatocyte cultures have higher rates of beta-oxidation of palmitate and lower rates of esterification to glycerolipid than human or guinea pig hepatocytes. The R-enantiomer of etomoxir (sodium 2-[6-(4 chlorophenoxy)hexyl]oxirane-2-carboxylate), a hypoglycaemic compound and inhibitor of carnitine palmitoyltransferase I, inhibited palmitate beta-oxidation in all three species, but the sensitivity to inhibition was highest in human hepatocytes and lowest in rat hepatocytes. The concentration causing half-maximal inhibition was approximately: 0.1 microM in human; 1 microM in guinea pig and 10 microM in rat hepatocytes. In human and in guinea pig hepatocytes the inhibition of beta-oxidation by R-etomoxir was associated with an increase in the esterification of palmitate but in rat hepatocytes R-etomoxir lowered the total rate of palmitate metabolism. The S-enantiomer of etomoxir had no significant effect on beta-oxidation or esterification of palmitate in any of the three species. It is concluded that there are significant differences between human, rat and guinea pig hepatocytes, not only in the relative partitioning of palmitate between beta-oxidation and esterification, but also in the sensitivity to an inhibitor of carnitine palmitoyltransferase I. PMID- 1930298 TI - Stereospecificity of the inhibition by etomoxir of fatty acid and cholesterol synthesis in isolated rat hepatocytes. AB - The racemates of substituted 2-oxiranecarboxylates are potent inhibitors of fatty acid oxidation and fatty acid and cholesterol synthesis. We show in the accompanying paper [Agius L, Peak M and Sherratt HSA, Biochem Pharmacol 42: 1711 1715, 1991] that only the R-enantiomer of etomoxir, a potent hypoglycaemic compound, inhibits fatty acid oxidation in hepatocytes. We demonstrate in this paper that although the R-enantiomer of etomoxir is esterified to its CoA-ester more readily than the S-enantiomer, both the R- and S-enantiomers are equally potent inhibitors of fatty acid and cholesterol synthesis from acetate in rat hepatocytes. The inhibition of fatty acid synthesis is not due to direct inhibition of fatty acid synthetase and the inhibition of cholesterol synthesis occurs at a site proximal to formation of mevalonate. Since the S-enantiomer inhibits fatty acid and cholesterol synthesis but not fatty acid oxidation the inhibition of the biosynthetic pathways is not coupled to inhibition of fatty acid oxidation. PMID- 1930299 TI - Interaction of metronidazole with Escherichia coli deoxyribonucleic acid. AB - To define the characteristics of the reported binding of metronidazole to DNA, we isolated the DNA from hypoxic incubation mixtures that contained both [14C]metronidazole and metronidazole-susceptible strains of Escherichia coli. Thus, either [2-14C]metronidazole or [1',2'-14C]metronidazole was incubated with either wild-type E. coli (strain AB1157) or a DNA repair mutant (strain SR58) that is highly susceptible to metronidazole. Approximately 0.02% of the radiolabel in the metronidazole was found to be associated with DNA isolated from both strains of bacteria, a percentage similar to that found to be associated with DNA from mammalian sources in a variety of in vitro and in vivo experiments performed by other investigators. The bound radioactivity was not diminished, however, when a great excess of non-radiolabeled metronidazole was included in the incubation mixture, indicating that the binding we observed was probably due to impurities in the radiolabeled metronidazole. We also examined the binding to DNA of a possible surrogate for the partially reduced form of metronidazole, 1 methyl-4-phenyl-5-nitrosoimidazole (5NO), that has been described previously. The binding of the tritiated form of 5NO to DNA was also found to be undiminished by the addition of carrier 5NO (a finding which does not refute the hypothesis that 5NO may serve as a surrogate for the study of the active form of metronidazole). These studies do not exclude the binding to DNA of either metronidazole or a possible surrogate of its active functionality, but they indicate that if such binding occurs, it must be limited to very few sites on DNA and hence will be difficult to characterize. PMID- 1930301 TI - Effects of adenosine analogues on ATP concentrations in human erythrocytes. Further evidence for a route independent of adenosine kinase. AB - Adenosine derivatives are frequently used in chemotherapy because of their potent antitumor, antiviral and antiparasitic activity. We investigated the metabolism of some adenosine analogues in adenosine deaminase inhibited normal and adenine phosphoribosyltransferase (APRT) deficient human erythrocytes. The ATP and GTP concentrations and the formation of unusual nucleotides were measured. Some of the analogues studied (tubercidin, 9 beta-D-arabinofuranosyladenine, 2' deoxyadenosine, 2-chloroadenosine, neplanocin A) were phosphorylated to the corresponding nucleoside triphosphates and this process was abolished by iodotubercidin--an adenosine kinase inhibitor. With the exception of 2' deoxyadenosine, nucleotide analogue formation was accompanied by ATP depletion. ATP decrease was not observed after adenosine kinase inhibition and ATP concentration even increased in the presence of 2'-deoxyadenosine, neplanocin A and 5'-iodo-5'-deoxyadenosine. However, the latter increment was not observed in APRT deficient erythrocytes. Bredinin, S-adenosylhomocysteine, deoxycoformycin and adenosine dialdehyde did not form nucleotide derivatives or exert any effects on ATP concentration. It is concluded that adenosine analogues can either enter the nucleotide pool via phosphorylation mechanisms, or may be converted to ATP by the pathways involving the intermediate formation of adenine. PMID- 1930300 TI - Inducibility of P450Coh by pyrazole and its derivatives. AB - Pyrazole and several of its derivatives increase the hepatic microsomal coumarin 7-hydroxylase to a variable extent. The strongest inducers are pyrazole itself and those derivatives which have a hydroxy group or a halogen at the 4-position of the molecule. The increase in coumarin 7-hydroxylase is due to an increase in the microsomal P450Coh and the corresponding mRNA. The increase of P450Coh by pyrazole and 4-hydroxypyrazole is selective because several other mono-oxygenase enzymes and the total P450 content are either not affected or even decreased. These include the testosterone 15 alpha-hydroxylase (P45015 alpha), a close structural analogue of P450Coh, which is induced only marginally by pyrazole and even decreased by 4-iodopyrazole, and P450ac which is decreased by pyrazole and 4 hydroxypyrazole. Introducing a methyl residue at the 4-position will alter the induction properties of the compound essentially bymaking it less selective for P450Coh. These results demonstrate the special selective action of pyrazole and some of its derivatives on the hepatic microsomal mono-oxygenase complex and the unique mode of regulation of the cytochrome P450Coh even within the same subfamily of cytochromes P450. PMID- 1930302 TI - Biliary excretion of polyethylene glycol molecular weight 900. Evidence for a bile salt-stimulated vesicular transport mechanism. AB - Polyethylene glycol molecular weight 900 (PEG-900) has been used as a marker of vectorial water transport into bile canaliculus. However, the mechanisms by which this compound is excreted have not been clarified. To gain more information on this process, we studied the biliary excretion of [3H]PEG-900 in rats during choleresis induced by canalicular choleretics. In addition, the effects of the microtubule inhibitors colchicine and vinblastine, and of the acidotropic agent chloroquine, on PEG-900 excretion were studied to determine whether a vesicular pathway is involved. Continuous i.v. infusion of either dehydrocholate (DHC, a non-micelle forming bile salt choleretic) or 4-methylumbelliferone (4-MU, a non bile salt canalicular choleretic) at stepwise-increasing rates [0.7, 1.0 and 1.2 mumol.min-1.(100 g body wt)-1] induced a gradual increment in bile flow, whereas a transient increment of [3H]PEG-900 excretion was observed only during DHC induced choleresis. Furthermore, studies in which two consecutive i.v. injections of DHC (10 mumol/100 g body wt) were administered showed that [3H]PEG-900 excretion induced by a second administration of DHC was 54% lower than that induced by the first one, despite a similar excretion in bile flow. Finally, colchicine (0.5 mumol/100 g body wt), vinblastine (0.5 mumol/100 g body wt) and chloroquine (50 mg/kg body wt) pretreatments inhibited the DHC-induced increment in biliary [3H]PEG-900 output, while DHC-induced choleresis was almost unaffected. Conversely, excretion of [14C]sucrose, when coadministered with [3H]PEG-900, was not impaired by the treatments. These results suggest that, unlike sucrose, PEG-900 excretion is not associated with canalicular water movements. Instead, it may be related to a vesicular transport process followed by a bile acid-stimulated discharge of secretory vesicles into bile through the lysosomal compartment. PMID- 1930303 TI - Effect of estrogenic and antiestrogenic triphenylethylene derivatives on progesterone and estrogen receptors levels of MCF-7 cells. PMID- 1930304 TI - Lauric acid hydroxylase activity and cytochrome P450 IV family proteins in human liver microsomes. PMID- 1930305 TI - Millimeter-wave effects on electric activity of crayfish stretch receptors. AB - The effects of super high frequency (SHF) microwaves (34-78 GHz) on rates of spontaneous firing of the slowly adapting, stretch-receptor neurons of crayfish were studied. Initially, irradiation of continuously perfused, fluid-cooled preparations at power densities to 250 mW/cm2 caused a transient decrease in the rate of spontaneous firing (the dynamic response). Subsequently, with extinction of the SHF field, the rate of firing increased, finally stabilizing at pre exposure levels (stationary phase). Rates of firing also increased when the receptor muscle was stretched, and they were inversely correlated with small, field-induced increases of temperature (approximately 1.5 degrees C). The response to SHF radiation did not depend on frequency if temperature of the medium was constant. No resonant peaks were found when the millimeter range of frequencies was scanned. PMID- 1930306 TI - Magnetic shielding induces early developmental abnormalities in the newt, Cynops pyrrhogaster. AB - Developing larvae of the Japanese newt, Cynops pyrrhogaster, were subjected for 5 days to a shielded environment in which the static magnetic field was about 10,000 times weaker (5 nT) than the geomagnetic norm, which ranges between 30 and 60 microT at the earth's surface. Larvae from non-cleavage to neurula stages were exposed under shielded or normal (control) conditions and then examined for evidence of developmental abnormalities either 1 day or 20 days after treatment. The magnetic shielding was associated with an increased incidence of somatic defects, especially in larvae that were examined 20 days after shielding. Bi headedness and intestinal protrusion were observed in magnetically shielded larvae but not in controls. Other abnormalities more frequently observed in shielded larvae were spinal curvature, malformed eyes, and retarded or blocked development. These data are among the first to illustrate the effects of magnetic field deprivation on a developing animal. PMID- 1930307 TI - Thermal and metabolic responsiveness of Japanese quail embryos following periodic exposure to 2,450 MHz microwaves. AB - Two studies were performed to determine if repeated exposure of the avian egg to microwaves can alter metabolism, temperature, and growth rate of embryos. Another aim was to supplement conventional heating with microwave heating and provide an optimal temperature for growth. Japanese quail (Coturnix coturnix japonica) eggs were exposed from day 1 through 15 of incubation (8 h/day) to sham or microwave (2,450 MHz) irradiation. Microwave exposures were at two power densities, 5 or 20 mW/cm2, and at three ambient temperatures (Tas), 30.0, 33.1, or 35.4 degrees C. Specific absorption rates for unincubated and 15-day-old incubated eggs were, respectively, 0.76 and 0.66 W kg-1 mW-1 cm-2 (i.e., 3.8 and 3.3 W/kg at 5 mW/cm2 and 15.2 and 13.2 W/kg at 20 mW/cm2). Eggs were concurrently sham exposed at each of five Tas, ranging from 27.9 to 37.5 degrees C. Tests were conducted during the 16th day of incubation (i.e., 1 day post-treatment), in the absence of microwaves, to determine metabolic rate of embryos and internal and external egg temperatures at different Tas. Repeated exposures to microwaves at 5 and 20 mW/cm2 at the same Ta (30 degrees C) increased wet-embryo mass on the 16th day by an average, respectively, of 9% and 61% when compared with predicted masses for embryos exposed at the same Ta in the absence of microwave radiation. There was no reliable indication, from post-treatment tests and comparisons with control embryos of similar mass, that repeated exposure to microwave radiation resulted in abnormal physiological development. Microwave radiation can be used to increase egg temperature and embryonic growth rate at Tas below normal incubation level without altering basic metabolic and thermal characteristics of the developing bird. PMID- 1930308 TI - A dosimeter for assessment of exposures to ELF fields. AB - There are currently no biological indicators of electromagnetic field exposure to aid investigation of the biological effects of ELF fields, but this hiatus is partly compensated for by the ease with which the external fields can be measured. The subject of this report is a small electronic instrument that can log electric-, magnetic-, and transient-field intensities of individual subjects for a duration of two weeks, thus allowing exposure to be assessed in considerable detail. A preliminary survey conducted with the instrument has shown clear differences in domestic and occupational exposures of specific groups. Simple analytical models can be fitted to the field-exposure data by adjusting a few parameters such as current, intensity, and distance. Such modeling may be increasingly useful as the data base on exposures expands. PMID- 1930309 TI - The present and future adequacy of rheumatology manpower. A study of health care needs and physician supply. PMID- 1930310 TI - The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. AB - Classification criteria for most of the disorders belonging to the spondylarthropathy group already exist. However, the spectrum of spondylarthropathy is wider than the sum of these disorders suggests. Seronegative oligoarthritis, dactylitis or polyarthritis of the lower extremities, heel pain due to enthesitis, and other undifferentiated cases of spondylarthropathy have been ignored in epidemiologic studies because of the inadequacy of existing criteria. In order to define classification criteria that also encompass patients with undifferentiated spondylarthropathy, we studied 403 patients with all forms of spondylarthropathy and 674 control patients with other rheumatic diseases. The diagnoses were based on the local clinical expert's opinion. The 403 patients included 168 with ankylosing spondylitis, 68 with psoriatic arthritis, 41 with reactive arthritis, 17 with inflammatory bowel disease and arthritis, and 109 with unclassified spondylarthropathy. Based on statistical analysis and clinical reasoning, we propose the following classification criteria for spondylarthropathy: inflammatory spinal pain or synovitis (asymmetric or predominantly in the lower limbs), together with at least 1 of the following: positive family history, psoriasis, inflammatory bowel disease, urethritis, or acute diarrhea, alternating buttock pain, enthesopathy, or sacroiliitis as determined from radiography of the pelvic region. These criteria resulted in a sensitivity of 87% and a specificity of 87%. The proposed classification criteria are easy to apply in clinical practice and performed well in all 7 participating centers. However, we regard them as preliminary until they have been further evaluated in other settings. PMID- 1930311 TI - Classification criteria revisited. PMID- 1930312 TI - The prevalence of antiphospholipid antibodies in women with recurrent spontaneous abortion, women with successful pregnancies, and women who have never been pregnant. AB - Antibodies to negatively charged phospholipids are associated with a predisposition to both arterial and venous thrombosis, recurrent fetal wastage, and thrombocytopenia. These associations have been reported in patients who do not fulfill criteria for connective tissue diseases. In this study, we determined the prevalence of antiphospholipid antibodies in 81 women who had had recurrent spontaneous abortion (3 or more fetal losses), in 88 women whose pregnancies were successful, and in 64 women who had never been pregnant. Antiphospholipid antibodies were found in 16% of women with recurrent spontaneous abortion, and at a statistically greater prevalence than in women who had successful pregnancies (7%) as well as those who had never been pregnant (3%). A false-positive VDRL and IgG anticardiolipin antibodies were more specific for fetal wastage than was either the lupus anticoagulant or IgM anticardiolipin antibodies. PMID- 1930313 TI - Retardation of radiologic progression in rheumatoid arthritis with methotrexate therapy. A controlled study. AB - We evaluated the effects of methotrexate (MTX) on radiographic changes of rheumatoid arthritis (RA) in the hands, wrists, and feet of 31 patients who completed at least 24 months of treatment. Radiographs were obtained at baseline and every 1 or 2 years thereafter. MTX was administered for 2-6 years (mean 3.9 years); the total dose was 1,925 mg (range 970-3,810 mg). The mean duration of disease at baseline was 8.1 years (range 1-26 years). Radiographs taken over 1-5 years during previous, clinically ineffective, gold therapy (mean 2.2 years) were available for 24 patients, and the changes over time were compared. During MTX treatment, the mean number of swollen joints decreased from 22.5 to 8.3 (40 joints evaluated), and the mean erythrocyte sedimentation rate decreased from 61.6 mm/hour to 28.4 mm/hour. Thirty-six (19%) of 190 joints with Larsen scores of 0 at baseline progressed to a score of 1 or 2 within 1 year of beginning MTX, whereas with gold, 37 (44%) of 89 joints progressed (P less than 0.001). Of 419 joints with Larsen scores of 1, 12.5% deteriorated within 1 year with MTX treatment, compared with 14.7% of 183 joints during gold therapy (P not significant). There were no between-treatment differences for joints with higher Larsen scores. During gold therapy, the mean Larsen index (score per joint) for the hand and wrist joints (18 joints counted) progressed from 1.45 to 1.82 over a mean of 22.1 months, and during MTX, from 1.82 to 1.97 over a mean of 48.0 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930314 TI - Levels of keratan sulfate in the serum and synovial fluid of patients with osteoarthritis of the knee. AB - We examined the relationship between serum and synovial fluid (SF) levels of antigenic keratan sulfate (KS) and the clinical, laboratory, and radiologic features of disease in 125 well-characterized patients with knee osteoarthritis (OA). KS was quantified by enzyme-linked immunosorbent assay, using an antibody specific for a highly sulfated epitope on KS chains; the results were calculated as equivalents of an international standard of KS from human costal cartilage. The mean level of serum KS (393 ng/ml) was significantly higher than those previously reported for populations of adults without OA. There was a wide scatter of serum KS values (range 156-912 ng/ml), with little correlation with clinical or radiologic features. Men had significantly higher levels than women (456 +/- 135 ng/ml versus 368 +/- 110 ng/ml, mean +/- SD), and there was a statistically significant but weak association with indicators of polyarticular involvement (number of symptomatic joints, Heberden's nodes, hip symptoms) in women. Despite the wide scatter of results in the population as a whole, individual levels of KS were stable for up to 4 consecutive years in the 9 patients studied. Levels of KS were much higher in SF (n = 25) than in serum, but the two were not correlated. There was an inverse correlation between radiographic evidence of cartilage loss and the level of KS in SF. The large variations in serum KS values suggest that this measure may not be of diagnostic significance among populations of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930315 TI - HLA and T cell receptor polymorphisms in pauciarticular-onset juvenile rheumatoid arthritis. AB - The immunogenetic basis of pauciarticular-onset juvenile rheumatoid arthritis is unclear. We therefore analyzed the HLA and T cell receptor genes present in a clinically well-defined group of patients. We found that the DR8 haplotype contributes most of the HLA-associated risk, although alleles at other loci contribute independently. A candidate disease-associated T cell receptor polymorphism, in contrast, was not identified in this population. Mechanistic implications of these findings are discussed. PMID- 1930316 TI - Kidney biopsy in systemic lupus erythematosus. II. Survival analyses according to biopsy results. AB - Renal biopsy specimens from 123 patients with systemic lupus erythematosus (SLE) seen between 1970 and 1984 were assessed according to the World Health Organization classification and according to the presence of proliferative, active, or chronic renal lesions. Survival analysis was used to study the determinants of mortality. Survival rates were higher for patients with minimal lesions, intermediate for patients with focal or diffuse proliferative nephritis, and low for patients with glomerular sclerosis. The presence of proliferative and chronic lesions was associated with a higher risk of dying. Renal biopsy results are helpful in predicting prognosis for all-cause mortality in patients with SLE. PMID- 1930317 TI - Effect of an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F on human immune responsiveness. AB - Tripterygium wilfordii Hook F (TWH) is a vine-like plant that grows in a wide area of south China. An alcohol extract of this plant known as T2 has been suggested to be effective in the treatment of rheumatoid arthritis (RA). To examine the mechanism by which this herbal remedy might be effective in RA, the capacity of T2 to alter human immune responsiveness in vitro was investigated. Human peripheral blood mononuclear cells were obtained from normal adults and separated into purified populations of monocytes, T cells, and B cells. T2 at 0.1 1 micrograms/ml inhibited antigen- and mitogen-stimulated proliferation of T cells and B cells, interleukin-2 (IL-2) production by T cells, and immunoglobulin production by B cells. T2 did not affect IL-2 receptor expression by T cells, IL 1 production by monocytes, or the capacity of monocytes to present antigen. Inhibition could not be accounted for by nonspecific toxicity. These results support the conclusion that T2 exerts a powerful suppressive effect on human immune responses. This action might account for its therapeutic effectiveness in RA. PMID- 1930318 TI - Suppression of collagen-induced arthritis by combination cyclosporin A and methotrexate therapy. AB - Louvain (LOU) rats were administered either methotrexate (MTX; 0.3 mg/kg/week or 0.8 mg/kg/week intraperitoneally), cyclosporin A (CSA; 4 mg/kg/day or 10 mg/kg/day continuous infusion via osmotic pump), or a combination of both agents. The rats were immunized with native type II collagen (CII) to determine the effects of these agents on collagen-induced arthritis, an animal model of rheumatoid arthritis. A significant decrease in the incidence (P less than 0.01) and severity of arthritis by clinical (P less than 0.05) and radiographic assessments (P less than 0.05) was found in recipients of combination therapy, compared with controls. Delayed-type hypersensitivity reactions to CII were measured on day 26, and production of IgG antibody to CII was measured on days 7, 14, and 26. IgG antibody was evident by day 7, and titers were near-maximal by day 14. Both delayed-type hypersensitivity and antibodies to CII were reduced in animals that received the higher dosage of CSA. Liver, kidney, and spleen specimens obtained from rats treated with CSA and MTX demonstrated no histologic abnormalities on light microscopy, compared with controls. These studies indicate that CSA and MTX in combination is a safe and effective therapy for collagen induced arthritis and may be useful in the treatment of rheumatoid arthritis. PMID- 1930319 TI - Secular changes in published clinical trials of second-line agents in rheumatoid arthritis. AB - The present investigation was undertaken to explore changes over time in the design and reporting of trials of second-line drugs in rheumatoid arthritis, in the characteristics of patients included in the trials, and in the sources of funding. We studied 105 trials of second-line agents for the treatment of rheumatoid arthritis, including placebo-controlled and comparative trials involving 8 different agents. Three time periods, 1945-1969, 1970-1979, and 1980 1989, were compared. We found little change in the standards for reporting on the design of trials or for reporting information on patient dropout and drug side effects, some increase in the complexity of the statistical methods used, but no increase in the use of power analysis (reported in only 13% of trials). The average age of patients in clinical trials has increased. In recent years, there has been a substantial shift from placebo-controlled to comparative trials, and it is increasingly common for trials to be financially supported by pharmaceutical companies. The possible effects of secular trends should be considered when combining or comparing results of trials conducted in different years. PMID- 1930320 TI - HLA-DPB1*0301 is a major risk factor for rheumatoid factor-negative adult rheumatoid arthritis. AB - HLA-DPB1 alleles were determined using the polymerase chain reaction and allele specific oligonucleotide probes in Caucasoid patients with rheumatoid arthritis (RA) and in healthy controls. DPB1*0301 was found to be increased in seronegative patients (50.0% versus 10.8% in controls; relative risk = 8.3, P less than 0.0001). With our previous finding that DPB1*0301 is increased in seronegative children with polyarticular-onset arthritis, the results suggest a relationship between this disease and seronegative RA in adults. PMID- 1930321 TI - A case of Sjogren's syndrome with repeatedly negative findings on lip biopsy. AB - We report a case of Sjogren's syndrome characterized by keratoconjunctivitis sicca, parotid swelling, reduced salivary flow, and abnormalities on nuclear scanning. Two labial gland biopsies showed complete atrophy. Biopsy of an enlarged submandibular gland revealed lymphoid follicles and glandular replacement consistent with the diagnosis of Sjogren's syndrome. This case supports the concept that a negative finding on labial biopsy does not rule out a diagnosis of Sjogren's syndrome. PMID- 1930322 TI - Allopurinol sensitivity in a patient with chronic tophaceous gout: success of intravenous desensitization after failure of oral desensitization. AB - Sensitivity to allopurinol, which occurs in 10-15% of patients, can seriously limit the drug's use in chronic tophaceous gout. Oral allopurinol desensitization has been advocated for sensitive patients in whom use of the drug is warranted. We report the successful use of intravenous allopurinol desensitization in a patient with chronic tophaceous gout in whom oral desensitization had previously failed. PMID- 1930323 TI - Serum antibody to retroviral gag proteins in systemic sclerosis. PMID- 1930324 TI - Rectal incontinence due to an unusual localization of the myositic process in the external sphincter of a patient with dermatomyositis. PMID- 1930325 TI - Chronic arthritis due to Mycobacterium avium complex infection in a patient with the acquired immunodeficiency syndrome. PMID- 1930326 TI - Aseptic meningitis in association with diclofenac treatment in a patient with systemic lupus erythematosus. PMID- 1930328 TI - Joint destruction in arthritis: metalloproteinases in the spotlight. PMID- 1930327 TI - D-penicillamine-induced lupus erythematosus. PMID- 1930329 TI - Phospholipase A2 is a major component of the salt-extractable pool of matrix proteins in adult human articular cartilage. AB - Adult human articular cartilage contains a component with an apparent molecular weight of 16 kd, which is extractable with high ionic strength buffers. This protein, which, in addition to lysozyme, is one of the most prominent components in salt extracts of adult cartilage, is not detectable in cartilage from newborns. We performed N-terminal sequence analysis to identify the protein. The amino acid sequence obtained for the first 20 residues was identical to that reported for phospholipase A2 (PLA2) from human placenta and human synovial cells. The extractable PLA2 was found to be active. The lack of PLA2 in salt extracts from newborn cartilage observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis was confirmed by the very low levels of PLA2 activity detectable in these preparations. PLA2 was clearly present in cartilage extracts from an 18-year-old subject and a 19-year-old subject, suggesting that its accumulation begins at some stage during the adolescent growth period. The enzyme does not appear to be released from cartilage matrix under normal physiologic conditions, and it is possible that the accumulation of PLA2 in maturing cartilage is a result of the decreased matrix turnover associated with the termination of skeletal growth. Whether PLA2 is active in the cartilage matrix, its precise localization, and its effects on the resident chondrocytes remain to be determined. PMID- 1930331 TI - Localization of tumor necrosis factor alpha in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis. AB - Using immunoaffinity-purified polyclonal anti-human recombinant tumor necrosis factor alpha (TNF alpha) F(ab')2 fragments and immunohistochemical techniques, the cells that make TNF alpha were localized in the inflamed synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Anti-TNF alpha antibody-stained cells were demonstrated in 9 of 11 RA and 2 of 4 OA but none of 5 normal synovial membranes examined. In RA, 26-64% of the lining layer cells were positive for TNF alpha. In the interaggregate area, 10-30% of the cells contained TNF alpha, often in a perivascular distribution, and up to 19% of the cells in lymphoid aggregates stained for TNF alpha. Some endothelial cells also stained with these antibodies. In OA tissues, the TNF alpha-containing cells were found predominantly in the deeper layer. Cells containing TNF alpha were also found at the cartilage-pannus junction in all 4 RA specimens examined. Double immunofluorescence analysis demonstrated that most TNF alpha-secreting cells in the RA synovial membrane expressed the monocyte/macrophage marker antigens CD11b and CD14, and a few expressed the T cell marker CD3. Our findings provide histologic evidence that TNF alpha is locally produced in the lining and deeper layers of the synovium by cells of the monocyte/macrophage lineage, supporting its role in inflammation. Further, our findings demonstrate that TNF alpha is produced by cells at the cartilage-pannus junction, which could affect chondrocyte metabolism, leading to the cartilage degradation in RA. PMID- 1930330 TI - Human synovial mast cell involvement in rheumatoid arthritis and osteoarthritis. Relationship to disease type, clinical activity, and antirheumatic therapy. AB - Mast cells were isolated by enzymatic digestion of synovium obtained from 48 patients with rheumatoid arthritis (RA) and 42 patients with osteoarthritis (OA). A significantly lower percentage of stainable synovial mast cells was obtained by tissue digestion from patients with clinically active RA compared with those with less active disease. The 54 patients treated with nonsteroidal antiinflammatory drugs had a significantly lower percentage of stainable synovial mast cells in cell suspension than did the other 36 patients. When anti-IgE antibody was used as a secretagogue in vitro, significantly greater histamine release was observed from synovial mast cells of RA patients compared with OA patients. Greater histamine release in response to anti-IgE was observed in the RA patients with more clinically active disease and those who were treated with prednisone, compared with RA patients without these features. Synovial mast cells of RA patients treated with a disease-modifying antirheumatic drug had a significantly lower mean histamine content than did cells from patients not receiving such treatment. Our data suggest that there are differences between synovial mast cells from tissues of patients with RA and OA and suggest that synovial mast cells may be activated in clinically active RA. In addition, the data indicate an effect of systemic antirheumatic therapy on mast cells isolated from synovium of patients with arthritis. PMID- 1930332 TI - Autoantibodies to human stress proteins. A survey of various rheumatic and other inflammatory diseases. AB - Unselected sera from patients with various rheumatic, inflammatory bowel, and autoimmune skin diseases (n = 268) were examined against human cell lysate by immunoblotting procedures, to determine the prevalence of autoantibodies to stress proteins (heat-shock proteins) hsp60 (homolog of Escherichia coli groEL and mycobacterial 65K antigens), hsp73, and hsp90. Using standard, sensitive and specific assay conditions, IgG and IgM autoantibodies to these stress proteins were not demonstrable, or were detected infrequently, in sera from control subjects (n = 36) and from patients with rheumatoid arthritis, Sjogren's syndrome, ankylosing spondylitis, Reiter's syndrome, systemic lupus erythematosus, and systemic sclerosis. Autoantibodies to hsp60 were relatively more common (greater than or equal to 20% of sera) in patients with mixed connective tissue disease, polymyositis/dermatomyositis, psoriatic arthritis, inflammatory bowel disease, epidermolysis bullosa acquisita, and bullous pemphigoid. Anti-hsp73 autoantibodies were detected in 20% or more of the sera from patients with Lyme disease and ulcerative colitis. Taken together, these data extend the spectrum of autoimmune and inflammatory diseases in which humoral anti-stress protein autoreactivity develops. However, the paucity of humoral autoreactivity to stress proteins in patients with systemic lupus erythematosus and rheumatoid arthritis argues against a direct role of anti-stress protein autoantibodies in the pathogenesis of these disorders. PMID- 1930333 TI - Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis. AB - We measured interleukin-6 (IL-6) levels in 70 serum samples obtained from 25 patients with systemic-onset juvenile rheumatoid arthritis (JRA), using the hybridoma cell line B9. Patients with systemic-onset JRA had significantly elevated serum IL-6 levels during active disease (mean +/- SD 92.1 +/- 75.1 hybridoma growth factor units/ml; P less than 0.00001 versus healthy age-matched controls), but not during remission. Serum IL-6 levels correlated with the extent and severity of joint involvement (P less than 0.001) and with platelet counts (P less than 0.05). Our data suggest that IL-6 plays a significant role in the pathogenesis of systemic-onset JRA. PMID- 1930335 TI - Familial erythema nodosum. AB - Erythema nodosum (EN) is a hypersensitivity reaction associated with many diseases. We describe a family in which 4 sisters had acute or recurrent EN. HLA typing showed a common haplotype in the affected members of the family. A review of familial EN and HLA distribution in EN is presented. PMID- 1930334 TI - Effect of medication on synovial fluid leukocyte differentials in patients with rheumatoid arthritis. AB - We compared leukocyte populations in synovial fluid samples from 45 rheumatoid arthritis patients, grouped according to medications taken. Seventeen of the 22 patients receiving only nonsteroidal antiinflammatory drugs had lymphocytes as the single predominant cell. None of the 23 patients receiving second-line agents had lymphocyte predominance. These findings may have important implications for drug mechanisms and must be considered in future studies of synovial fluid. PMID- 1930336 TI - Effects of body weight restriction on the development and progression of spontaneous osteoarthritis in guinea pigs. AB - Hartley albino guinea pigs develop spontaneous osteoarthritis (OA) of the knee joint. A study was done to determine the importance of body weight in the pathogenesis of this disease. Two groups of 20 male guinea pigs each were maintained on the same diets. The control group was allowed ad libitum feed consumption and the other group was restricted to 30-35 gm of feed per day. Ten animals from each group were killed at 9 months of age to evaluate histologic features of the knee joints. The severity of the OA lesions was reduced by 40%, in conjunction with a 28% decrease in body weight, in the diet-restricted group. The remaining animals were killed at 18 months of age. Those in the diet restricted group had a 56% reduction in severity of lesions, with a 29% decrease in body weight. These results indicate that body mass in guinea pigs, as in humans, is an important predisposing factor for the development of spontaneous OA of the knee. PMID- 1930337 TI - Strategies for reducing excess morbidity and mortality in blacks with systemic lupus erythematosus. AB - The epidemiology of systemic lupus erythematosus suggests that the excess morbidity and mortality in blacks with the disease is related to lower socioeconomic status. Poverty and factors associated with poverty are powerful predictors of poor outcome in a variety of chronic diseases, and lupus appears to be no exception. A body of studies in other illnesses suggests ways to neutralize, at least partially, the disadvantages of lower socioeconomic status, even though the root causes of poverty may be insurmountable. These include improving access to quality health care; targeting educational programs to promote recognition and understanding of the disease and the comorbid conditions that affect outcome; implementing programs to improve self-monitoring and adherence to medical regimens; developing opportunities to facilitate homemaking, childrearing, and working outside the home; and applying psychosocial interventions to enhance self-confidence and social support. Improved access to quality health care may actually lead to a decrease in health care costs. PMID- 1930338 TI - Rheumatic diseases among Civil War troops. AB - There are extensive existing medical records of Federal Civil War troops. More than 160,000 cases of "acute rheumatism" occurred among these soldiers, and acute rheumatic fever was known to be the main cause. Infectious arthritides were frequent but not understood; gout was rare. "Chronic rheumatism" was diagnosed more than 246,000 times; prolonged rheumatic fever and reactive arthritis following dysentery were probably the major causes. Over 12,000 soldiers were discharged because of chronic rheumatism, many with "lumbago," which was probably spondylarthropathy. PMID- 1930339 TI - Vitamin E and rheumatoid arthritis. PMID- 1930340 TI - Vitamin E in arthritis. PMID- 1930341 TI - Chinese herbal medicine: camouflaged prescription antiinflammatory drugs, corticosteroids, and lead. PMID- 1930342 TI - Bilateral nervus axillaris palsy after computed tomography of the spine. PMID- 1930343 TI - Effects on night-time motor activity and performance in the morning after midazolam intake during the night. AB - The hypnotic action and residual effects of a single night-time dose of midazolam (Ro 21-3981, Dormicum, 7.5 mg; CAS 59467-70-8) were investigated in young, healthy adults. The subjects went to bed at the habitual time and were awakened 3 h later for drug or placebo intake. Then they were allowed to continue their sleep. Motor activity was continuously recorded by a wrist-worn activity monitor. In comparison to placebo, prolonged night-time immobility periods were more frequent after midazolam. Sleep tended to be perceived as more quiet and as less interrupted by awakenings. 15 min after awakening in the morning, the subjects felt more relaxed after midazolam than after placebo. Performance assessed 2 h after awakening by a psychomotor test showed no decrement. The results show that a 7.5-mg dose of midazolam taken in the first half of the night has a significant hypnotic action without impairing psychomotor performance in the morning. PMID- 1930344 TI - [Effect of a special kava extract in patients with anxiety-, tension-, and excitation states of non-psychotic genesis. Double blind study with placebos over 4 weeks]. AB - Clinical Efficacy of a Kava Extract in Patients with Anxiety Syndrome/Double blind placebo controlled study over 4 weeks. In a randomized, placebo-controlled double-blind study two groups each containing 29 patients with anxiety syndrome not caused by psychotic disorders were treated for a period of 4 weeks with kava extract WS 1490 (Laitan) 3 x 100 mg/day or a placebo preparation. Therapeutic efficacy was assessed by the Hamilton-Anxiety-Scale (main target variable), the Adjectives-List and the Clinical-Global-Impression-Scale (secondary target variables) after 1, 2 and 4 weeks of treatment. The HAMA overall score of anxiety symptomatology revealed a significant reduction in the drug receiving group already after one week of treatment. This difference between the two groups of patients increased in the course of the study. The results of the secondary target variables were in agreement with the HAMA-score and demonstrate the efficacy of WS 1490 in patients with anxiety disorders. No adverse experiences caused by the medication were noted during the 4 week administration of WS 1490. PMID- 1930345 TI - Vascular effects of isosorbide dinitrate on the common carotid artery in human volunteers. AB - The effects of 20 mg of orally administered isosorbide dinitrate (ISDN, Isocoronal R; CAS 87-33-2) on cerebral hemodynamics were investigated in 14 normal healthy volunteers (average age 32.6 years). The common carotid artery hemodynamics in the right supraclavicular region were measured using an ultrasonic quantitative flow measurement system. 2 h after drug administration, systolic blood pressure (15.5 mmHg, p less than 0.001) and mean blood pressure (7.2 mmHg, p less than 0.02) decreased significantly, but diastolic blood pressure did not change. A decrease in blood flow volume (2.85 ml/s, p less than 0.001) and blood flow velocity (7.00 cm/s, p less than 0.001), and an increase in mean vessel diameter (0.19 mm, p less than 0.05), and volume elasticity (0.68 x 10(5) dyn/cm2, p less than 0.02) were observed with ISDN. Mean vessel diameter increased gradually and reached its maximum at 4 h. However, the other maximal effects of ISDN were exerted at about 2 h. The ultrasonic quantitative flow measurement system was found to be useful in the case of repetitive measurements of the common carotid artery hemodynamics. It has been demonstrated that ISDN (20 mg/subject, p.o.) increases the diameter of the common carotid artery, although it decreases the blood flow in the common carotid artery. PMID- 1930346 TI - Clinical efficacy of nifedipine and other calcium antagonists in patients with primary esophageal motor dysfunctions. AB - In this paper the pharmacodynamic effects of calcium channel blockers (verapamil, nifedipine, diltiazem, fendiline, nitrendipine, nimodipine, and nisoldipine) on esophageal motility in man and their clinical effects in patients with various forms of primary esophageal motility disorders are critically analysed and summarized. The evaluation of efficacy and safety is mainly focused on nifedipine (Bay a 1040, Adalat; CAS 21829-25-4), since it has been best documented clinical pharmacologically and therapeutically in this field. Nifedipine and--with varying potency--the other calcium antagonists reduce effectively the increased lower esophageal sphincter pressure (LESP) and abnormally high and prolonged peristaltic and nonperistaltic contractions in the esophageal body in patients with achalasia, diffuse esophageal spasm (DES), and other disorders which may cause angina-like chest pain and/or dysphagia. Pharmacodynamic effects on esophageal motility are closely correlated with the plasma concentration of nifedipine in healthy volunteers and in patients. However, a final judgement on the therapeutic value of these compounds in esophageal motor abnormalities cannot be given due to conflicting results from clinical studies with fairly small numbers of patients and varying study designs. Among the different calcium antagonists investigated nifedipine represents the best investigated and the most suitable compound for the treatment of primary hypertensive esophageal motor disorders. PMID- 1930347 TI - General pharmacology of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride. Effects on central nervous and sensory systems and other functions. AB - The effects of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotension I converting enzyme inhibitor, on the central nervous systems, were studied in experimental animals. Benazepril hydrochloride (3 or 10 mg/kg/d, p.o. for 14 days) dose-dependently inhibited the increase in the blood pressure caused by continuous norepinephrine (NE) infusion in spontaneously hypertensive rats (SHR) and suppressed in seizures induced by a monoamine oxidase inhibitor, tranylcypromine in NE infused SHR. Benazepril hydrochloride transiently increased spontaneous motor activity in mice, tended to inhibit acetic acid-induced writhing in mice and decreased fast wave sleep and slow wave deep sleep on EEG in cats at a high dose of 100 mg/kg p.o. However, benazepril hydrochloride at the same dose showed no effect on other central nervous and sensory systems in experimental animals. PMID- 1930348 TI - Antihypertensive action of the novel angiotensin converting enzyme inhibitor benazepril hydrochloride in hypertensive rat models. AB - Single or repeated administration of benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4), a novel angiotensin I converting enzyme inhibitor, (0.3-10 mg/kg p.o.) caused significant antihypertensive effects in renal and spontaneously hypertensive rats (SHR). The antihypertensive effects of benazepril hydrochloride was about 3 times as potent as that of captopril in these models. Single administration (0.3-3 mg/kg p.o.) of benazepril hydrochloride and enalapril maleate showed an equipotent antihypertensive effect in SHR. Benazepril hydrochloride (3-30 mg/kg p.o.), however, showed no clear effect on the blood pressure and heart rate in normotensive or DOCA/salt hypertensive rats. PMID- 1930349 TI - Effect of (+/-)-2-(dimethylamino)-1-[[o-(m-methoxyphenethyl)phenoxy] methyl]ethyl hydrogen succinate on experimental models of peripheral obstructive disease. AB - Peripheral obstructive disease in tail or hind limb was experimentally induced by intravenous injection of kappa-carrageenin or intra-arterial injection of sodium laurate in rats, and the suppressive effect of (+/-)-2-(dimethylamino)-1-[[o-(m methoxyphenethyl)phenoxy] methyl]ethyl hydrogen succinate (MCI-9042, CAS 125926 17-2) on the peripheral obstructive diseases was examined. The injection of kappa carrageenin induced a thrombotic infarction of the tail vessel in rats. The administration of MCI-9042 dose-dependently suppressed the peripheral infarction with an ED50 value of 16 mg/kg p.o. Ticlopidine, a reference antiplatelet drug, did not affect the peripheral infarction even at 50 mg/kg p.o. Cyproheptadine, however, an S2-serotonergic antagonist, potently suppressed the peripheral infarction with an ED50 of 3.5 mg/kg p.o. After the injection of sodium laurate into the femoral artery in rats peripheral lesions of the paw were generated and extended. MCI-9042 significantly prevented the progression of the disease at doses of 10 mg/kg p.o. and above. When the daily administration of MCI-9042 was started from 1 day after the laurate injection, it was also effective as well as by pretreatment. Ticlopidine was significantly effective only at 100 mg/kg p.o. as pretreatment. From the present study, it is considered that platelet-derived serotonin plays an important role in the development of peripheral obstructive disease and MCI-9042 suppressed the disease through its S2-serotonergic antagonism. PMID- 1930350 TI - Vasodilator and angioprotective activity of 1-ethyl-1-hydroxyalkyl octahydroindolo[2,3a]quinolizine derivates. AB - The blood flow enhancing activity of the homologue series of "trans" racemic 1 ethyl-1-hydroxyalkyl-1,2,3,4,6,7,12,12b-octahydroindolo[2, 3a]quinolizine (1) was studied in anesthetized dogs. It was found that the femoral vasodilator activity is the strongest for 1b, and decreases if the carbon chain is shortened (1a) or lengthened (1c). Also, a breakdown of vasodilation was observed with the racemic "cis" derivative (2). After resolution of 1b the optically active compound 3 retained the dilator capacity while 4 isomer lost it. Hence 3 (RHG-2981, vintoperol, CAS 106498-99-1) was selected for detailed pharmacological study. Dose-response studies performed in anesthetized dogs showed that vintoperol 0.03 mg/kg (i.v.) was more potent as peripheral vasodilator than buflomedil or pentoxifylline at doses ranging from 1 to 15 mg/kg. Similar results were observed during a 4-week cross-over test of maximal running distance of femoral ligated mice. The running performance, as measured by the rotating drum, showed a linear increase in the untreated control group (UCG) as a consequence of every day testing (= intensive endurance training). After bilateral femoral occlusion the maximal running distance of the mice fell off, and despite daily training it stagnated. If 0.3 or 1 mg/kg/d vintoperol or 10 mg/kg/d pentoxifylline was administered orally 4 days after the bilateral femoral occlusion, the maximal running distance increased. In the case of 1.0 mg/kg of vintoperol applied daily, the rate of enhancement approached, or even overtook, that of the UCG. 0.3 mg/kg/d of vintoperol showed less activity, however, this result is still about twice better than the effect of 10 mg/kg/d pentoxifylline. PMID- 1930351 TI - Influence of garlic powder on cutaneous microcirculation. A randomized placebo controlled double-blind cross-over study in apparently healthy subjects. AB - In a randomized placebo-controlled double-blind cross-over study it could be shown that 5 h after the administration of garlic powder (Kwai, Sapec; total dose of 900 mg garlic powder) a significant increase in capillary skin perfusion by 55% occurs in the healthy volunteers. Placebo did not cause any changes. The difference between the two study phases is also significant. The increased erythrocyte velocity results from vasodilation of precapillary arterioles which increases diameter of erythrocyte column by an average of 8.6%. Simultaneously inflow of interstitial fluidity accompanied by a significant decrease in haematocrit and plasma viscosity occurs (rheoregulation). PMID- 1930352 TI - General pharmacology of the four gastrointestinal motility stimulants bethanechol, metoclopramide, trimebutine, and cisapride. AB - The pharmacological profile of bethanechol (CAS 674-38-4), metoclopramide (CAS 364-62-5), trimebutine (CAS 39133-31-8) and cisapride (CAS 81098-60-4) was studied in a series of simple pharmacological tests in rats and dogs. Bethanechol stimulated both gastric emptying and intestinal propulsion but displayed also the well-known behavioral effects of a direct muscarinic acetylcholine receptor agonist. Metoclopramide showed the profile of a centrally active dopamine D2 antagonist. In addition, metoclopramide displayed a stimulant effect on spontaneous gastric emptying in rats, an effect that could not be related to dopamine D2 antagonism. The only effect observed with trimebutine was protection from castor oil diarrhea, probably due to its reported interaction with peripheral opiate receptors. Cisapride was a potent stimulant of gastric emptying in rats, 7 times more potent than metoclopramide. Cisapride was also a very specific gastrokinetic, over a large dose range (specificity ratio: greater than or equal to 20) devoid of effects indicative for direct interaction with dopamine or acetylcholine receptors. The relationship between the differential activity profiles of the compounds in the present study and differences in their mechanism of action and side-effect liability is discussed. PMID- 1930353 TI - [Protection from gastroduodenal adverse effects of acetylsalicylic acid with ranitidine. An endoscopic controlled double-blind study of healthy subjects]. AB - Ranitidine protects against gastroduodenal mucosal damage associated with low dose ASA therapy/Endoscopically evaluated double-blind study in healthy volunteers In a randomized double-blind crossover study the gastroduodenal tolerability of 300 mg ASA mane (8 a.m.) has been evaluated in the presence of 300 mg ranitidine nocte (8 p.m.) or placebo in 10 healthy volunteers using upper GI-endoscopy. The treatment periods lasted 14 d. Endoscopic controls were performed at entry, and repeated at day 7 and day 14. At entry the mean endoscopic score averaged 0.9 +/- 0.1 in the ASA/placebo-group and 0.8 +/- 0.1 in the ASA/ranitidine-group. 300 mg ASA mane induced in the placebo-experiments marked gastroduodenal ulcerations both at day 7 and day 14 (7.3 +/- 1.3 and 8.2 +/- 2.1, respectively). Concommittant administration of 300 mg ranitidine nocte afforded almost full protection against 300 mg ASA mane both on day 7 and day 14 (1.6 +/- 0.4 and 1.7 +/- 0.5, respectively) (p less than 0.05). These data suggest that nocturnal coadministration of ranitidine 300 mg reduces almost completely gastroduodenal lesions evoked by acetylsalicylic acid 300 mg mane. PMID- 1930354 TI - Preliminary pharmacokinetics of a new pyridopyrimidine derivative. AB - This paper describes the preliminary pharmacokinetic studies of 4-anilino-2 methylthiopyrido[2,3-d]pyrimidine (MD-39-AM) following a single administration of the compound to male rats via different routes (intravenous and oral) in the dose range of 6-24 mg.kg-1. The plasma level versus time plots after intravenous and oral administration to male rats can well be described by an open two-compartment model. The product was rapidly absorbed and peak concentrations in plasma were reached before 1 h after a single oral administration whatever the dose studied. The absolute bioavailability calculated on the basis of AUC0-infinity after intravenous and oral administration was estimated to be about 90%. Plasma levels found at higher doses than 6 mg/kg suggest that the product kinetics is dose dependent. PMID- 1930355 TI - Demonstration of flufenamic acid in histological sections. AB - A simple method is described to show the transdermal penetration of flufenamic acid (CAS 530-78-9) into the skin of laboratory animals. After topical application of gels and creams containing flufenamic acid the substance exerts a fluorescent painting in corium and subcutis of histological slides. This effect needs the chemical reaction between the test substance and sulphuric acid in synthetic resin sections. PMID- 1930356 TI - In vitro investigations on the antineoplastic effect of hexadecylphosphocholine. AB - The in vitro antineoplastic activity of hexadecylphosphocholine (HPC, CAS 58066 85-6) on methylnitrosourea (MNU)-induced mammary carcinoma in Sprague-Dawley rats and human mammary carcinoma was investigated with the modified Hamburger-Salmon Colony-Assay (HSCA). The effect of HPC was also compared with ilmofosine (alkyllysophospholipid derivative) and N-(2-chloroethyl-N-nitroso-N'-2 hydroxyethylurea (HECNU). Moreover, the modified HSCA was performed with bone marrow cells and KB cells. In this investigation, no specific antineoplastic effect of the test compounds on MNU-induced mammary carcinoma and human mammary carcinoma was found in HSCA. Thus the antineoplastic activity of the compounds could not be compared on these cell types. In vitro, effects were only observed in bone marrow and KB cells at a very low concentration. The in vitro effect of HPC on mammary carcinoma cells, evaluated through HSCA, did not predict the effect of HPC in vivo. The reason has remained unknown but some hypotheses are discussed. Because of the contrary results of HPC in vitro and in vivo, it should be pointed out that drug development in this class of compounds mainly has to depend on in vivo experiments. PMID- 1930357 TI - Increasing alkaline DNase activity with substrate specificity for denaturated DNA after high dose methotrexate therapy. AB - After high dose methotrexate (CAS 59-05-2) therapy of children with non metastatic osteosarcoma the activity of an alkaline DNase with substrate specificity for denaturated DNA increases in lymphocytes and PHA-stimulated lymphocytes. The DNase activity is probably involved in the process of DNA repair. The enzyme has an isoelectric point of pI 5.9, the pH optimum is 8.5, and Mg++ is necessary for activation. Two weeks after the end of the therapy the DNase activity is comparable to the activity of controls. The determination of the alkaline DNase activity can represent a parameter to control side effects of a cytostatic therapy. It is an indirect way to demonstrate therapy induced DNA damage. PMID- 1930358 TI - Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man. AB - An experimental evaluation of citrulline malate (Stimol, CAS 54940-97-5), an anti fatigue compound, was undertaken in man and in the animal in order to study the pharmacological activity of the substance at hepatic and renal level. In man, the protocol involved a double-blind randomized, placebo-controlled cross-over technique. The study in the animal was blind and placebo-controlled with two randomized parallel groups. Results showed that citrulline malate stimulates hepatic ureogenesis and favorizes the renal reabsorption of bicarbonates. These metabolic actions had a protective effect against acidosis and ammonia poisoning and explain the anti-fatigue properties of citrulline malate in man. PMID- 1930359 TI - Undergraduate alcohol education. PMID- 1930360 TI - Adult women's drinking in Israel: a review of the literature. AB - This article presents a review and critique of research on Israeli Jewish women's drinking. It has been prepared in an attempt to bring together the results of all Israeli studies dealing with Jewish women's drinking. It summarizes, on the basis of a review of all Israeli alcohol research in the professional literature in Hebrew and English, women's drinking practices over the last 42 years (May 1948 May 1990) with emphasis on the last decade. Three main areas of interest (alcohol dependent women in treatment, drinking habits of women in special populations, and drinking habits and attitudes of women in the general population) have been elucidated by looking at three periods: the late 40s-60s, the 70s, and the 80s. The 60s and 70s are characterized by studies concerning pathological drinking patterns among women in clinical and treatment settings, and the 80s are characterized by research in the general population. The review concludes with a call for more investigation and topics for further study are discussed. PMID- 1930361 TI - Effect of ethanol administration on the in vivo kinetics of thiamine phosphorylation and dephosphorylation in different organs. I. Chronic effects. AB - The effects of chronic ethanol administration on different steps in the metabolism of thiamine (T), thiamine mono- (TMP) and pyrophosphate (TPP) were determined in vivo in the liver, kidney, heart, skeletal muscle and small intestinal mucosa. The radioactivity of T and its phosphoesters was measured in plasma and in the selected organs under steady-state conditions and at fixed time intervals (0.25-240 hr) after an i.p. injection of Thiazole-[2-14C]-thiamine (30 micrograms: 1.25 microCi) in rats chronically (35 days) ethanol-treated (daily dose of 4.7 g kg-1 body wt by gastric gavage). Two types of controls were used: pair-fed rats treated with a sucrose solution isoenergetic with ethanol, and water-treated rats. A nutritionally adequate diet, which supplied an excess of thiamine, was given to the rats, producing a virtually steady content of thiamine compounds in the tissues. The analytical data obtained were elaborated using appropriate compartmental mathematical models, which allowed the fractional rate constants, turnover rates and turnover times to be calculated. Alterations in thiamine metabolism were modest and differed according to the organs. The most widespread modification was to facilitate the entry of T (small intestine, kidney and heart) or TMP (small intestine and kidney), while no significant change of T and TMP release was seen. Sucrose had minimal effect in both steps. Enzymatic transformations of thiamine were likewise marginally affected. A general trend toward a slower T pyrophosphorylation and a faster T phosphate dephosphorylation was observed in the small intestine, kidney, heart and liver. Skeletal muscle was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930362 TI - Disturbances in myocardial creatine kinase following ethanol administration to rats--trials of prevention by allopurinol, desferrioxamine and propranolol. AB - A significant decrease in myocardial creatine kinase (CK) activity is apparent 2 hr after an acute ethanol load (2.3 g/kg, i.p.) in the rat. A lower dose (1.15 g/kg, i.p.), as well as ethanol addition in vitro up to 50 mM, do not affect this activity. Pretreatment with allopurinol (146 mumols/kg, i.p.) given at 16 hr and at 30 min before ethanol (2.3 g/kg) or with desferrioxamine (152 mumols/kg, i.p.) 30 min before ethanol failed to prevent the ethanol-induced decrease in CK activity. By contrast, propranolol (17 mumols/kg, i.p.), administered 30 min before ethanol elicited an enhanced CK activity in both control and ethanol treated rats. This finding is likely related to the beta-blocking action and/or antioxidant properties of propranolol. Chronic ethanol intake (18% in calories) for 4 weeks also induced a decrease in myocardial CK activity, which could play a role in the pathogenesis of alcoholic cardiomyopathy. PMID- 1930363 TI - Red cell caesium, lithium and selenium in abstinent alcoholics. AB - Using inductively coupled plasma source mass spectrometry, we have studied the red cell element concentrations of alcoholic subjects with different periods of abstinence before testing. We found consistently elevated red cell caesium concentrations and also reduced red cell selenium concentrations. These may represent persistent abnormalities in oxidation/anti-oxidation mechanisms, and red cell caesium in particular may be a long-term marker of alcohol dependence. Erythrocyte lithium, cerium and boron concentrations were also reduced in the abstinent alcoholic groups. PMID- 1930364 TI - Acidic phospholipids in synaptosomal plasma membranes during repeated episodes of physical ethanol dependence in the rat. AB - The effects of repeated episodes of ethanol intoxication and the hyperexcitable state of withdrawal on the synaptosomal concentration of acidic phospholipids were studied in rats. There was no indication that cumulative changes in the synaptosomal acidic phospholipid composition in general occurred during multiple episodes of ethanol intoxication and withdrawal. There was, however, a statistically significant decrease in acidic phospholipid concentration (phosphatidylinositol; PI) in synaptosomal membranes from animals revealing spontaneous convulsive behaviour during ethanol withdrawal. Hypothetically this may reflect an inability to increase acidic phospholipid membrane content and thus to adaptively increase the seizure threshold during withdrawal. PMID- 1930365 TI - Application of a three-compartment model to a study of the effects of sex, alcohol dose and concentration, exercise and food consumption on the pharmacokinetics of ethanol in healthy volunteers. AB - A recently developed three-compartment model for the absorption and elimination of ingested alcohol was applied to re-analyse a study on the effects of various factors known to influence the blood-alcohol curve. The absorption and elimination of alcohol after drinking diluted alcohol were studied in healthy volunteers under strictly standardized conditions. The factors studied were sex, dose, concentration, physical exercise, meal consumption before drinking, energy content and composition of the meal, and time of drinking in relation to meal consumption. Gastric emptying and absorption from the small intestine were assumed to be first-order, and a possible delay (or acceleration) of gastric emptying was accounted for by a feedback-control parameter. The elimination process was assumed to follow Michaelis-Menten kinetics. Clear effects were observed of sex and dose, and aspects of meal consumption on absorption and elimination of alcohol. The ingestion of a meal prior to the intake of alcohol reduced both the gastric emptying rate and absorption efficiency of alcohol, increased the gastric emptying delay and reduced the rate of elimination. The absorption efficiency was even lower when the alcohol was consumed during the meal instead of after the meal. Using alcohol during the meal accelerated gastric emptying and reduced absorption efficiency as well as rate of elimination. High fat meals resulted in the highest gastric emptying rate and rate of absorption from the small intestine, whereas high-protein and high-sucrose meals resulted in the lowest gastric emptying rate. Simultaneous consumption of a high-sucrose meal and alcohol increased gastric emptying delay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930366 TI - A community screening test for high alcohol consumption using biochemical and haematological measures. AB - A discriminant function based on a number of biochemical and haematological tests from an extended multiple biochemical analysis and full blood count, together with weight, smoking status and systolic blood pressure is developed. The function was far more effective at detecting high alcohol use (greater than 40 g ethanol per day) than serum gamma-glutamyl transpeptidase (GGT) or the Short Michigan Alcoholism Screening Test (SMAST) in a community sample of adult males. When classifying high alcohol consumption by GGT only, several division criteria were considered, the most effective being at 40 i.u./l. In terms of identifying high alcohol consumers, rather than alcoholics, the SMAST was no better than GGT, and both had unacceptably low sensitivity (49%, 51%) and poor performance on other measures, thus limiting their use as community screening tools. The discriminant function, however, had an estimated community sensitivity of 78%, was similarly high on other performance measures, and would perform satisfactorily as a community screening tool, particularly in situations where there was a tendency for individuals to under-report their alcohol consumption. PMID- 1930367 TI - Comparison of questionnaire and biochemical markers to detect alcohol abuse in a West Indian population. AB - This study bears upon the respective validity of biochemical markers and questionnaires to detect alcohol abuse in a population with a high rate of alcohol-linked neurological complications. GammaGT and apoprotein AII were the most powerful of eight studied biochemical markers in detecting two-thirds of excessive drinkers. The CAGE questionnaire identified 74% of moderate drinkers and 94% of excessive drinkers with a life style and patterns of alcohol consumption different from previously tested target populations. The joint association of the CAGE questionnaire and apoprotein AII detected more than 9 out of 10 moderate or excessive drinkers defined on the basis of a quantity-frequency grid. PMID- 1930368 TI - Alcoholic intake in a small rural village. AB - Eight hundred and eighteen (400 males and 418 females), randomly selected inhabitants of an economically depressed rural village in the south of Tenerife, have been analysed with respect to their daily alcoholic intake and its relationship to sex, age, marital status, educational and economical level, job, tobacco use and the CAGE and brief MAST tests. Five hundred and four (68.9%) consumed alcoholic beverages, while 254 (31.1%) were teetotal; 12.1% of the subjects aged more than 15 years (23.85% of the males and 1.4% of the females) consumed 'risk' amounts of alcoholic beverages (more than 80 g/day and 40 g/day respectively). Mean ethanol consumption was 37.9 +/- 2.1 g/day for the male sex and 3.9 +/- 0.6 g/day for the female. Maximum mean ethanol consumption (60.9 g/day) was observed among the males aged 55-64 years. The distribution of the population according to the amount of ethanol consumed fits into Lederman's curve, most of the individuals being consumers of small amounts of ethanol. Male sex, middle age, married status, unskilled job, low educational level, and tobacco use were all related to a higher ethanol consumption. CAGE and brief MAST tests detected only 40.5% and 47% respectively of the subjects with 'risk' levels of alcohol consumption. PMID- 1930369 TI - Patterns of drinking in Wales. AB - As part of a larger survey of health-related behaviours, 8441 Welsh men and women aged 18-64 years provided information relating to their overall consumption of alcohol, frequency of binge drinking (defined as consumption of at least half the recommended weekly limits, less than or equal to 21 units for men, less than or equal to 14 units for women) per occasion, and changes in consumption over time. Key findings indicate 29% of men and 9% of women report drinking in excess of the recommended safe limits, whilst 28% and 8% respectively report binge drinking at least once weekly. Such drinking is not, however, confined to heavy drinkers: 14% of men and 5% of women who drink within the recommended safe limits also report binge drinking at least once weekly. These and other results are discussed in relation to future health promotion initiatives. PMID- 1930370 TI - Possible clinical implications of reduced cardiac vagal function in chronic alcoholics. PMID- 1930371 TI - Unilateral partial hemi-laminectomy for the removal of extra- and intramedullary tumours and AVMs. PMID- 1930372 TI - Organization of the primary transportation of head injuries and other emergencies in the Federal Republic of Germany. PMID- 1930373 TI - Advances in drug delivery systems and applications in neurosurgery. PMID- 1930374 TI - Is there any future for robots in neurosurgery? PMID- 1930376 TI - AAOHN. Code of ethics and interpretive statements. PMID- 1930377 TI - Substance abuse in the workplace. PMID- 1930375 TI - Aspects of the medical management in aneurysmal subarachnoid hemorrhage. PMID- 1930378 TI - Alcohol and other drug abuse. Current perspectives for occupational health nurses. AB - 1. Trends in alcohol, drug, and tobacco use indicate that the upward surge of the 1960s and 1970s has subsided, but the amount of drug use in this country is still higher than in any other industrial nation. Risk factors associated with age, gender, culture, and family point to a significant increase in the number of individuals in the work force with a substance abuse problem. 2. The etiology of alcohol and other drug addictions is a subject of controversy. One position adheres to biological determinants of disease, another adheres to psychological disorders. 3. Implications for nurses involve effective teaching/learning strategies that range from didactic content emphasizing long term consequences of the disease to specific methods of employee instruction. PMID- 1930379 TI - Drugs and alcohol in the workplace. AB - 1. In response to increased costs of drug abuse due to decreased productivity by impaired workers, many corporations, either voluntarily or under federal mandate, have adopted a drug free workplace policy. 2. The main components of an anti-drug program include: management commitment, development of a drug free workplace policy, separate training programs for supervisors and employees, an Employee Assistance Program, and written drug testing procedures. 3. Signs and symptoms of the alcohol and drug abuser in the workplace are subtle. A supervisor or occupational health nurse must be astute to recognize the problem and intervene to provide assistance and counseling before a crisis occurs. PMID- 1930380 TI - Involuntary chemical addiction treatment. EAP implications for occupational health nurses. AB - 1. Measuring treatment effectiveness is problematic when a substance abuser does not enter treatment voluntarily. Furthermore, clients' goals and EAPs' goals for recovery may be in conflict. 2. It is preferable to determine treatment effectiveness by those changes in behavior, lifestyle, and quality of life that each substance abuser considers important for recovery. 3. The author found that substance abusers' goals progress through four stages: denial, dependence, behavior change, and life planning. 4. The recovering substance abuser who returns to work requires continuous follow up by the occupational health nurse. Client stage needs to be assessed and care must be planned accordingly. PMID- 1930381 TI - The impaired nurse. Organizational and professional models of response. AB - 1. Two models of response, organizational and professional, affect the impaired nurse, who is both an employee and a professional. 2. The organizational model of response uses an Employee Assistance Program (EAP) to detect and intervene with impaired employees. 3. The professional model of response involves mechanisms established through the board of nursing, including posttreatment monitoring. 4. When both models are available, linking mechanisms such as coordinators, policies, and reentry practices can combine the strengths of each model. PMID- 1930382 TI - Research funding. PMID- 1930383 TI - Evaluating needlestick injuries in nursing personnel. Development of a questionnaire. AB - 1. Needlestick injuries are the most common type of occupational injury experienced by nursing personnel. Sixty percent to 90% of needlestick injuries in medical centers are incurred by nurses. 2. Future increases in patient acuity and more advanced technology are likely to increase the risk of nurses experiencing accidental needlesticks. 3. Needle devices that require disassembly of equipment, especially those related to intravenous piggybacks and prefilled cartridge syringes, are placing nurses at an increased risk for injury. 4. Needle-less devices or devices which keep the needle recessed except during intended use have been designed. The assessment instrument can identify needlestick injury incidence and trends and can be used to evaluate and justify the increased costs of purchasing new safety equipment. PMID- 1930384 TI - The Roy Adaptation Model. Health teaching about osteoporosis. AB - 1. Osteoporosis has an impact on quality of life and places a financial strain on the health care system. Occupational health nurses can play a key role in health education about osteoporosis because they have the most frequent contact with at risk persons. 2. The Roy Adaptation Model presents a holistic approach for assessment of persons at risk and allows for planning of nursing interventions. 3. A concerted effort must be made to ensure persons at risk engage in health promoting strategies to decrease the incidence of the disease. PMID- 1930385 TI - The health fair as an effective health promotion strategy. AB - 1. Effective health fairs must provide appropriate health education. 2. Screenings must have associated education and be performed by qualified screeners with properly calibrated equipment. 3. Environmental stress reduction and privacy are important factors to consider when planning a health fair or screening. 4. All fairs and screenings are important and should not be coordinated haphazardly. PMID- 1930386 TI - Evaluation of selected new drugs: 1990. AB - 1. The new drugs approved by the Food and Drug Administration during 1990 are presented. 2. The pharmacologic actions, indications, dosages, precautions, and adverse reactions of selected new medications are considered. 3. The occupational health nurse can use this information to help clients understand and follow drug treatment plans. PMID- 1930387 TI - Minnesota workplace drug testing. Analysis of policy and procedures. AB - 1. An employer's decision whether to drug test or not was found to correlate with the size of the company and how extensively the employer perceives a drug abuse problem exists among its work force. 2. A company's drug testing program must be designed, implemented, and evaluated within a medical-legal framework. This includes issues of: confidentiality, employee actions that trigger a drug test, the presence of a drug and alcohol policy, communicating the program to employees and unions, the employee's rights, the consequences of an employee's positive drug test, and the procedures to be followed when collecting a specimen. 3. Future studies need to explore the issue of dealing with job performance problems; in particular, the cost and effectiveness of employee drug testing vs. the use of discipline alone. PMID- 1930388 TI - Maternal rights in the workplace. PMID- 1930389 TI - Artificial respiration in the dog by percutaneous, bilateral, phrenic nerve stimulation. AB - Artificial respiration was produced in 11 anesthetized dogs using trains of short duration stimuli (1 msec with a frequency of 35/sec), applied to needle electrodes placed bilaterally at the base of the neck. The tips of the needles were in close proximity to the phrenic nerves. In all cases, the inspired volume increased with an increase in stimulus intensity. Typically, it required 5 to 10 volts (peak) to produce an inspired volume equal to spontaneous tidal volume. The maximum inspired volumes ranged from 1.27 to 4.31 times the tidal volume. PMID- 1930390 TI - Chloral hydrate for emergent pediatric procedural sedation: a new look at an old drug. AB - Chloral hydrate has been time honored for pediatric procedural sedation, but its efficacy in sedation for emergency department (ED) procedures is unreported. It is hypothesized that chloral hydrate is safe and effective for ED pediatric sedation. Ninety-five consecutive children ranging from 1-10 years and requiring procedural intervention in a municipal teaching hospital ED were included in a nonrandomized controlled trial. Patients with respiratory depression, somnolence, allergy, multisystem trauma, head injury, or abdominal pain were excluded. Forty two subjects received chloral hydrate 25 to 50 mg/kg orally at physician discretion, and 53 subjects served as controls. Cooperation with procedural completion was rated by the treating physician using the four-point sedation scoring system modified from Moody et al (1 = poor, 4 = excellent). The two groups' sedation scores were compared by the Mann Whitney U test with significance at P less than .05. Age-related subgroups of children were similarly compared. The treatment group achieved sedation score of 2.86, whereas controls had sedation score of 2.75 (P = 0.63, beta error 20% at 0.37 score difference). Subgroup analysis of children less than 6 years old (2.95 experimental versus 2.57 control) and less than 4 years old (3.00 experimental versus 2.32 control) reveals statistically significant differences (P less than .0001 and P = .01, respectively) in favor of higher sedation scores in the chloral hydrate group. Time to sedation was 42.7 minutes, time to recovery was 42.0 minutes, and no adverse drug effects were noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930391 TI - Cervical spine movement during airway management: cinefluoroscopic appraisal in human cadavers. AB - The objective of this study was to determine which airway maneuvers cause the least cervical spine movement. A controlled laboratory investigation was performed in a radiologic suite, using eight human traumatic arrest victims who were studied within 40 minutes of death. All subjects were ventilated by mask and intubated orally, over a lighted oral stylet and flexible laryngoscope, and nasally. Cinefluoroscopic measurement of maximum cervical displacement during each procedure was made with the subjects supine and secured by hard collar, backboard, and tape. The mean maximum cervical spine displacement was found to be 2.93 mm for mask ventilation, 1.51 mm for oral intubation, 1.65 mm for guided oral intubation, and 1.20 mm for nasal intubation. Ventilation by mask caused more cervical spine displacement than the other procedures studied (ANOVA: F = 9.298; P = .00004). It was concluded that mask ventilation moves the cervical spine more than any commonly used method of endotracheal intubation. Physicians should choose the intubation technique with which they have the greatest experience and skill. PMID- 1930392 TI - Plasma cocaine and tetracaine levels following application of topical anesthesia in a swine laceration model. AB - Standard TAC (0.5% tetracaine, 0.05% epinephrine, and 11.8% cocaine) solution is finding increased use as a topical anesthetic for lacerations. The extent of systemic absorption of TAC components and their resultant physiologic effects are unclear. Absorption of cocaine or tetracaine may result in serious toxicity. The investigators hypothesized that there are no measurable plasma cocaine or tetracaine levels after application of TAC in a swine laceration model. After an overnight fast 10 domestic swine underwent tracheostomy, mechanical ventilation, femoral venous, and arterial cannulation. Maintenance anesthesia with intermittent thiopental and pancuronium was provided to maintain stage III anesthesia. Heart rate (HR), arterial pressure (BP), plasma cocaine, and tetracaine levels were measured at intervals for 180 minutes. Five milliliters of TAC was applied for 15 minutes to a standardized facial laceration in experimental swine (n = 5). Randomly labeled plasma samples were placed in vials containing 2% sodium fluoride and 1% potassium oxalate, immediately refrigerated, and analyzed for cocaine and tetracaine using gas chromatography and mass spectroscopy. Significant changes in HR and mean BP, compared with baseline values, were analyzed using Dunnett's multiple range test. Plasma cocaine levels were measurable in all experimental swine after 10 minutes, while no tetracaine was detectable. No significant differences in HR or BP changes were observed between experimental and control subjects. Application of standard TAC solution results in measurable plasma cocaine levels, but not tetracaine. Further studies into anesthetic formulation, as well as timing and technique of application, are required before consensus on optimal emergency departmental use of topical anesthesia can be achieved. PMID- 1930393 TI - Numerators, denominators, and survival rates: reporting survival from out-of hospital cardiac arrest. AB - This study demonstrates the effect of different denominators on the survival rate from out-of-hospital cardiac arrest. We retrospectively analyzed data from a cardiac arrest surveillance system in King County, Washington during the years 1976 to 1988, and calculated survival rates using eight different definitions of denominators. The eight survival rates ranged from 16% to 49% discharge from hospital. The denominator for the lowest survival rate included all cases of cardiac arrest for whom emergency medical services personnel started cardiopulmonary resuscitation. The denominator for the highest survival rate included: all cases of presumed cardiac etiology; first recorded rhythm was ventricular fibrillation; collapse witnessed; cardiopulmonary resuscitation started by bystanders within 4 minutes; and definitive care provided within 8 minutes. The definition of cases included in the denominator can dramatically effect the resultant survival rate. There must be national and international agreement about definitions of denominators for valid cross community comparisons. PMID- 1930394 TI - Acute myocardial infarction presenting as flank pain and tenderness: report of a case. AB - Studies have demonstrated that 4% to 10% of patients with chest pain and acute myocardial infarction (AMI) are discharged from the emergency department. The patient with an atypical presentation of AMI is difficult to diagnose and has been demonstrated to have an associated increased risk of morbidity and mortality. A case is reported of a patient with AMI presenting to the emergency department with flank pain and tenderness, mimicking acute renal colic. PMID- 1930395 TI - Ciprofloxacin interaction with sodium warfarin: a potentially dangerous side effect. AB - Ciprofloxacin, a quinolone antibiotic which exhibits minimal side effects and has broad antimicrobial spectrum, is being used frequently to treat various infections. A patient is reported who had previously maintained a stable prothrombin time on Coumadin for 5 years, and who exhibited a marked prolongation of prothrombin time when placed on ciprofloxacin for gastroenteritis. PMID- 1930396 TI - An unusual complication of radial head fractures. AB - Radial head fractures are a fairly common injury secondary to falls on the outstretched forearm. Specific combinations of injuries involving radial head fractures and triceps tendon avulsion have been reported. Compartment syndromes secondary to distal forearm fractures are common; however fracture of the radial head rarely results in an acute compartment syndrome. A patient is reported with the combination of radial head fracture and triceps tendon avulsion complicated by the acute development of a compartment syndrome. PMID- 1930397 TI - Isolated clavicle fracture with associated pneumothorax: a case report. PMID- 1930398 TI - Safety of immediate treadmill testing in selected emergency department patients with chest pain: a preliminary report. AB - To determine the feasibility and safety of an immediate, symptom-limited, treadmill test on selected emergency department (ED) patients, a convenience sample of 28 patients underwent an exercise treadmill test (ETT) within the first several hours after hospital arrival using the modified Bruce protocol. Patients were included in the study if they presented with otherwise unexplained chest pain consistent with (but not characteristic for) angina pectoris and had a normal electrocardiogram. A negative ETT was seen in 23 of 28 patients, and five of 28 patients had a positive ETT. No patients had serial enzyme or electrocardiogram evolution suggestive of myocardial ischemia, and all patients with a negative ETT were discharged after a full inpatient evaluation designed to rule out unstable coronary disease. At a mean follow-up period of 6.1 months there has been no cardiac morbidity or mortality in the patients with negative ETTs. It was concluded that early ETTS of selected ED patients with chest pain is safe, and an exercise test administered during the ED visit which is negative can preclude unnecessary hospitalization. PMID- 1930399 TI - Alkalinity of non-industrial cleaning products and the likelihood of producing significant esophageal burns. AB - Alkaline cleaning products are a cause of serious esophageal injury. Over time, legislation has diminished the concentration of many such non-industrial solutions and solids; however several products presently do not list either the pH or relative concentrations of alkaline constituents. This study measures the pHs of several non-industrial cleaning products containing either ammonium chloride, sodium hydroxide, or potassium hydroxide. Three pH measurements were performed on each of 10 non-industrial alkaline cleaning products (eight liquid, two solid). Two 0.1% ammonium chloride solutions had pHs of 12.06 +/- 0.00 and 12.06 +/- 0.01, whereas a pH of 12.43 +/- 0.00 was recorded in a 0.2% ammonium chloride solution. Concentrations of sodium hydroxide and potassium hydroxide were listed on only one of five liquid cleaning product labels. The pHs for these five products varied between 12.83 +/- 0.009 and 13.5 +/- .0.2. The pHs of three sodium hydroxide solutions differed from values reported in Micromedex (Micromedex Inc, Denver CO) by up to 0.32 pH units. Ten percent (v/v) solutions of two solid lye products had pHs of 13.62 +/- 0.008 and 13.74 +/- 0.02. The investigator found that selected non-industrial cleaning products, including ammonia solutions, retain the ability to cause clinically important esophageal damage. PMID- 1930400 TI - Urinary bladder distention presenting as venous obstruction and hypovolemic shock. AB - A confused patient presented with hypovolemic shock and signs of arterial and venous obstruction of the left lower extremity; the correct diagnosis of urinary retention was made after phlebography. Vascular complication in bladder distention is unusual and diagnosis may require radiologic investigation. PMID- 1930401 TI - Knotting of a nasogastric tube: a case report. PMID- 1930402 TI - Untoward reaction to adenosine therapy for supraventricular tachycardia. AB - Adenosine, a naturally occurring nucleoside that slows conduction through the atrioventricular node, has recently been approved for the treatment of supraventricular tachycardia. It has been shown to convert patients with supraventricular tachycardia to sinus rhythm in up to 92% of cases. Its intravascular half-life of only 10 seconds and absence of reported serious side effects have made adenosine an attractive antiarrhythmic agent. This report describes two cases in which significant side effects from the administration of adenosine were encountered including: (1) prolonged sinus arrest with syncope, and (2) syncope with prolonged bradycardia and hypotension. Emergency physicians should be cognizant of the potential complications resulting from adenosine administration, and should be prepared to deal with them when using this newly available agent. PMID- 1930403 TI - Differential diagnosis of chest discomfort and general approach to myocardial ischemia decision making. PMID- 1930404 TI - Transesophageal echocardiography in emergency medicine and critical care. PMID- 1930405 TI - Management strategies in wide QRS complex tachycardia. PMID- 1930407 TI - Pediatric emergency care: an annotated bibliography of the recent literature. PMID- 1930406 TI - Crisis intervention following disasters: are we doing enough? (A second look). AB - During mass casualty events the consequences of psychological trauma are an important cause of morbidity among survivors and rescue personnel. Data available from military and civilian disasters over the past 70 years has shown a fairly predictable ratio of acute and severe emotional trauma associated with mass casualty events. Long-term morbidity from psychological trauma can rival or exceed that of the physical injuries of survivors. Psychological intervention reduces this morbidity, and early psychological intervention is more effective before adverse psychological symptoms have fully developed. However, the widely accepted value of early psychological intervention is not universal, with controversy over the degree of emotional trauma expected after a large-scale catastrophic mass casualty event, as well as the number of victims and the effectiveness of immediate psychological intervention. Some research even suggests that there is only a minor risk of acute emotional trauma among survivors of a major disaster. The United States faces the possibility of mass casualties from national disasters--particularly earthquakes--and conventional warfare. It has been predicted that 100,000 major injuries requiring hospitalization and 20,000 deaths would result from the maximum plausible natural disaster incident in the United States. Pentagon planners expect thousands of servicemen to be evacuated to the United States for hospitalization on a daily basis during an overseas conventional war. With these estimates of potential casualties, it is imperative that this controversy be resolved as quickly as possible. The National Disaster Medical System recently established plans to provide immediate treatment for psychological trauma to disaster survivors and rescue personnel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930408 TI - Cocaine and chorea. PMID- 1930409 TI - Transcortical motor aphasia due to a subdural hematoma. PMID- 1930410 TI - Lingual tonsillitis: an uncommon cause of airway compromise responsive to epinephrine. PMID- 1930411 TI - Radiographic clue to luxatio erecta. PMID- 1930412 TI - Lumbar puncture for febrile seizures: do we need a "maxim"? PMID- 1930413 TI - Long-term consequences of CNS treatment for childhood cancer, Part II: Clinical consequences. AB - Survival of children with brain tumors has improved over the past 20 years due in part to advances in surgery, radiation, and most recently chemotherapy. The long term adverse effects of radiation and chemotherapy on these children is the subject of this report. In Part I, we reviewed the pathologic consequences of radiation, including leukoencephalopathy, radiation necrosis, and radiation myelopathy as well as the oncogenic effects of both radiation and chemotherapy. Part II addresses the long-term consequences of radiation and chemotherapy on intellectual and endocrine function. Risk factors for the development of both endocrinopathies and intellectual dysfunction include age at the time of radiation, volume and dose of radiation, site of tumor, and use of adjuvant chemotherapy, in particular methotrexate. Early recognition of these complications and treatment, where indicated, will measurably improve the quality of-life of children treated for brain tumors. The national cancer groups are currently attempting to limit these long-term adverse effects by taking risk factors into account when formulating new treatment regimens. PMID- 1930414 TI - Management of febrile seizures: survey of current practice and phenobarbital usage. AB - A questionnaire survey was mailed to all members of the Child Neurology Society in North America to determine current methods used by pediatric neurologists in the management of febrile seizures and the influence of public awareness of phenobarbital side-effects on practice. Responses were received from 574 of 869 deliverable questionnaires (66%). The mean number of febrile seizures treated by respondents was 42 +/- 58 (mean +/- S.D.), of which 22 +/- 36 were simple and 19 +/- 31 were complex. In the control of the acute, continuing febrile seizure, intravenous phenobarbital, lorazepam, and diazepam were equally preferred and phenytoin was used infrequently. For intermittent administration by parents, diazepam was prescribed by 20% for seizure prevention and by 31% for control of seizure recurrence. Long-term phenobarbital was prescribed by 89% for prevention of complex febrile seizures and by 43% for simple febrile seizures. Parental anxiety was a factor in the prescription of intermittent or long-term therapy by 67% of respondents. PMID- 1930416 TI - Attention deficit disorder: association with familial-genetic factors. AB - The etiology of attention deficit disorder and hyperactivity (ADDH) is controversial because both biologic and social factors have been postulated. To study such factors, we undertook a referral study based on an entire cohort (N = 6,950) of children born in Jerusalem in 1976. Of 479 children referred for learning disabilities, hyperactivity, and behavioral problems, 381 were available for study. Information regarding obstetric, developmental, and family histories was obtained by a detailed, structured interview. A DSM-III-based questionnaire for ADDH was completed by parents and teachers. Each child underwent neurologic examination and 133 had IQ testing. Of these children, 145 fulfilled the criteria for ADDH. Our results revealed a number of significant familial-genetic factors: boys outnumbered girls by 3:1, 30% of ADDH children had siblings with learning disabilities (P less than .001); and ADDH children clustered within families of North African descent (P less than .001). The only significant developmental factor was delayed language development. Of numerous pre- and peri-natal factors investigated, only intrauterine growth retardation was significantly associated with ADDH. No correlation was found between ADDH and IQ, parental age, years of education, profession, and language spoken at home. Our study supports the hypothesis that familial-genetic factors are contributory to ADDH. PMID- 1930415 TI - 201Tl/99mTc-HMPAO SPECT imaging of treated childhood brain tumors. AB - To assess whether thallium-201 thallous chloride (Tl) can detect childhood tumors and whether diagnostic effectiveness improves with combined blood flow imaging, 28 children (1.0-18.6 years) were studied using single photon emission computed tomography (SPECT): Tl (1.3-1.8 mCi intravenously), followed in 13 of the patients by technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO; 8-18 mCi intravenously). Tl-uptake was markedly increased with histologically confirmed recurrent brain tumors (N = 12). Tl-avid tumors comprised several histologic types, including 6 astrocytomas/gliomas as well as nonastrocytic neoplasms, such as medulloblastoma and ependymoma. A questionable false-positive study was observed with a treated medulloblastoma. Tl failed to detect 5 tumors (i.e., 2 medulloblastomas, 1 ependymoma, 1 malignant schwannoma, and initially 1 low-grade astrocytoma). The sensitivity and specificity of 201Tl-SPECT for detection of childhood brain tumors was 76.9% and 93.3%, respectively. The mean tumor-to normal brain ratio for Tl was 2.5 +/- 0.5 (N = 7). In some of the patients, 201Tl SPECT allowed a more precise assessment of the functional state of the tumor than was possible with computed tomography and magnetic resonance imaging. HMPAO distribution was variously normal, increased or decreased at the site of tissue abnormality, and abnormal blood flow was demonstrated in the remaining neuraxis, in 3 of the 7 patients. Changes in tissue perfusion did not correlate with Tl findings, but were evaluated in only one false-negative study. PMID- 1930417 TI - Timing of maintenance phenytoin therapy after intravenous loading dose. AB - The specific timing of maintenance phenytoin therapy in children has not been addressed. Prevention of a subtherapeutic phenytoin level is important for seizure control. We devised a protocol using an 18 mg/kg loading dose of phenytoin with serial levels (obtained after 2,6,12 hours) and analyzed the results in 20 consecutive patients. A therapeutic level (greater than 10 micrograms/ml) was present in all patients at 2 hours, in 16 of 20 at 6 hours, and in 10 of 20 at 12 hours. The patients were divided into 2 groups by the 12 hour levels: group I: therapeutic level; and group II: subtherapeutic level. The mean 2-hour level in group I was 22.7 micrograms/ml versus 15.6 micrograms/ml in group II (P less than 0.001). The mean decline in plasma concentration in individual patients was 0.7 micrograms/ml/hr in group I versus 1.02 micrograms/ml/hr in group II (P less than 0.05). We now use the 2-hour level to decide the timing of maintenance phenytoin therapy and have devised an equation to estimate the duration of the therapeutic range. Phenytoin can be administered at 12 hours when the 2-hour level is satisfactory or earlier when the 2-hour level indicates that a subtherapeutic level will occur. PMID- 1930418 TI - Neurologic, cognitive, and linguistic features of infants after early stroke. AB - Fourteen infants who suffered early localized, unilateral cerebral infarction were studied to examine the neurologic status of these children, to investigate psychomotor, cognitive, and language abilities, and to examine relationships between behavior and lesion severity. The patients underwent a neurologic examination and were evaluated with the Bayley Scales of Infant Development and the Sequenced Inventory of Communication Development. Motor development was not significantly delayed despite the presence of hemiparesis in most infants (which correlated with lesion severity). There was no evidence of marked delay in global cognitive functioning but one-half of the children were delayed in psychomotor functioning. Evidence of receptive and/or expressive language delay also was observed in one-half of infants and toddlers. PMID- 1930419 TI - Central nervous system tuberculosis in children. AB - The incidence of tuberculosis in the United States is increasing in all age groups; 5% of all of these patients have central nervous system involvement. We studied childhood central nervous system tuberculosis between 1979 and 1989 and reviewed the literature for patients up to 14 years of age. The small number of patients reported in this country results in delayed diagnoses because of reduced awareness. Cranial computed tomography within 1 week of initial symptoms may reveal basilar enhancement, hydrocephalus, or infarction. When combined with cerebrospinal fluid findings atypical for common bacterial infection, these radiographic findings support the prompt initiation of antituberculous therapy. Prophylactic considerations are also discussed. PMID- 1930420 TI - MRI and CT findings in Krabbe disease. AB - The progression and characteristics of magnetic resonance imaging (MRI) and computed tomographic (CT) findings in 3 patients with infantile Krabbe disease (i.e., globoid cell leukodystrophy or galactocerebroside beta-galactosidase deficiency) are reported. We obtained initial CT and MRI studies when patients demonstrated hyperirritability and hypertonicity. The following results facilitated early diagnoses: increased density in the thalami, corona radiata, and cerebellar cortex on CT and plaque-like, high signal intensity in the periventricular region and cerebellar white matter on MRI T2-weighted images. After severe motor and mental deterioration and spasticity had developed, progressive brain atrophy, low density in the white matter, and calcification like, symmetric, punctate high-density areas in the corona radiata were evident on CT and high signal intensity in T2-weighted images and low signal intensity in T1-weighted images in the white matter were present on MRI. In particular, linear patterns were observed in the centrum semiovale on MRI. PMID- 1930421 TI - Four adult Rett patients at an institution for the handicapped. AB - We report the clinical, laboratory, and magnetic resonance imaging results of 4 adult patients (ages 25, 26, 29, and 35 years) with stage IV Rett syndrome. The patients were diagnosed at an institution for the handicapped. Two of them had been previously diagnosed as having cerebral palsy. All were microcephalic and had seizures, although the frequency of seizures decreased with advancing age. Three patients had scoliosis. Magnetic resonance imaging demonstrated marked craniofacial disproportion in 2 patients, bilateral atrophy of the frontotemporal lobes in 3, and cerebellar atrophy in 1. The cerebrospinal fluid concentrations of biopterin and homovanillic acid did not differ significantly in these Rett syndrome patients from age-matched controls. PMID- 1930422 TI - Cerebellar infarct: late complication of the Fontan procedure? AB - Cardiac disease is present in approximately 30% of children with stroke. Other case reports have documented stroke in patients who have previously undergone the Fontan procedure for correction of tricuspid atresia. Most of these strokes have occurred in the immediate postoperative period. There has been one report of a cerebral infarction 3 1/2 months after surgery. We report a child with superior cerebellar artery distribution infarction after undergoing the Fontan procedure 24 months previously. Previous reports of stroke in patients having undergone the Fontan procedure and possible etiologies for these strokes are discussed. We believe our patient had the longest procedure-to-stroke interim yet reported. PMID- 1930423 TI - Congenital muscular dystrophy in Marinesco-Sjogren syndrome. AB - The histochemical and immunocytochemical findings of biopsied muscle in a 2-year old girl with Marinesco-Sjogren syndrome are reported. Muscle histology consisted of mild muscular dystrophy, such as that found in limb-girdle or non-Fukuyama congenital muscular dystrophy. By immunocytochemical stain using anti-dystrophin antibody, Duchenne and Becker muscular dystrophies were excluded. In addition to characteristic clinical features, including ataxia, congenital cataract, and psychomotor retardation, muscle involvement is essential to the diagnosis of Marinesco-Sjogren syndrome. PMID- 1930424 TI - Seizures and cerebritis associated with administration of OKT3. AB - The development of a self-limited aseptic meningitis usually following the first dose administration of OKT3 therapy (an anti-pan-T-cell monoclonal antibody) in the treatment of renal transplantation rejection is well-documented. This report describes a patient with renal transplantation rejection who developed lateralizing seizures and cerebritis documented by magnetic resonance imaging. These findings were associated with the initiation of OKT3 therapy. To our knowledge, both cerebritis and seizures have not been described in association with OKT3 therapy. PMID- 1930425 TI - Infantile spasms in COFS syndrome. AB - Cerebro-oculo-facial-skeletal (COFS) syndrome is a rare, autosomal recessive syndrome characterized by microcephaly, microphthalmia and/or cataracts, neurogenic arthrogryposis, and multiple congenital anomalies. A term female infant with COFS syndrome who developed infantile spasms at the age of 3 months is reported. The patient had a good response to intramuscular ACTH with disappearance of infantile spasms and resolution of the hypsarrhythmic pattern on electroencephalography succeeded by a slow, synchronous pattern. Modified hypsarrhythmia returned after ACTH therapy was discontinued. Infantile spasms have not previously been reported in association with COFS syndrome and are a potentially treatable aspect of the disease. This patient may add to the clinical spectrum of COFS syndrome or may have a variant. PMID- 1930426 TI - Correction of cerebrospinal fluid copper in Menkes kinky hair disease. AB - A patient with Menkes Kinky Hair disease was treated with infusions of copper histidine which resulted in normal copper values in the cerebrospinal fluid. This tends to confirm the in vitro data that copper is transported into the central nervous system complexed with histidine or other similar ligands. PMID- 1930427 TI - CHARGE and Joubert syndromes are different. PMID- 1930428 TI - VEP and predicting outcome in birth asphyxia. PMID- 1930429 TI - The introduction of midwifery in Ontario, Canada. AB - Midwives in Ontario, Canada, currently have no legal status. After an announcement in 1986 that the government would recognize them, an extensive planning period ensued. Groups of health care providers, consumers, and government representatives were active participants in formulating plans to integrate midwives into the centrally organized health care system in Ontario. Efforts to introduce legislation, establish a regulatory framework, and develop an educational program are well developed, but legalized practice must yet be realized. PMID- 1930430 TI - Midwifery--A family doctor's view from Quebec. PMID- 1930431 TI - Drug abuse and pregnancy: some questions on public policy, clinical management, and maternal and fetal rights. AB - An estimated 9202 drug-exposed infants were born in the United States in 1986 according to the National Center for Health Statistics; the number increased to 13,765 in 1988. These figures were substantially underreported, however, notes the 1990 report by the U.S. General Accounting Office (GAO) (1). It surveyed 10 hospitals, two each in Boston, Chicago, Los Angeles, New York, and San Antonio, accounting for 44,655 births, of which approximately 4000 resulted in drug exposed infants in 1989. Maternal cocaine use was estimated to range from below 1 to 12 percent among the 10 hospitals. The GAO report concluded that the number of these infants born nationwide each year could be "very high," and that in these five cities the unavailability of drug treatment and lack of adequate prenatal care are contributing to the problem (1). Two health professionals and a health lawyer were invited to respond to some questions about the problems of cocaine and substance abuse by pregnant women and how maternity caregivers, health and social service agencies, law, and society are dealing with the issues. PMID- 1930433 TI - Roundtable: postterm pregnancy. Part II. In the final analysis. PMID- 1930432 TI - Roundtable: postterm pregnancy. Part II. Antenatal testing and candid reassurance. PMID- 1930434 TI - Every pregnant woman should be offered a test for human immunodeficiency virus. PMID- 1930435 TI - "Commentary: arguments against episiotomy and in favor of squatting for birth". PMID- 1930436 TI - 1989 U.S. cesarean section rate steadies--VBAC rate rises to nearly one in five. AB - The 25 years of rising cesarean delivery rates in the United States may have finally run their course. In 1989 the rate of 23.8 cesareans per 100 deliveries was not significantly different from 24.7 in 1988, 24.4 in 1987, or 24.1 in 1986. The 1989 primary rate of 17.1 first cesareans per 100 women with no previous cesarean was also not significantly different from 17.5 for 1988, or 17.4 for 1987 and 1986. The percentage of vaginal births after cesarean section per 100 deliveries showed a remarkable rise between 1988 and 1989--from 12.6 percent in 1988 to 18.5 percent in 1989. Data are from the National Hospital Discharge Survey conducted by the National Center for Health Statistics, Centers for Disease Control. PMID- 1930437 TI - Prenatal education in a high-risk population: the effect on birth outcomes. AB - This case-control investigation examined the relationship between absence of specific educational content during prenatal care and risk of adverse birth outcomes. A total of 1484 women from three regions with high rates of low birthweight and infant mortality participated in structured postpartum interviews. Analyses were performed for both the full sample and three regional subsamples. For the full sample an adjusted risk ratio of 2.87 (95% CI = 1.75, 4.71) was noted between risk of preterm low birthweight and lack of advice to call the health provider if preterm labor were suspected. For one subsample an adjusted risk ratio of 2.50 (95% CI = 1.11, 5.60) was noted between the risk of preterm low birthweight and lack of education on the signs and symptoms of preterm labor. This study reinforces a body of literature that stresses the importance of appropriate prenatal care in preventing preterm low birthweight. It further suggests that adequacy measures of prenatal care should reflect quality and content as well as timing and number of prenatal visits. PMID- 1930438 TI - Grassroots strategies for promoting maternal and infant health. AB - For the past four years, grassroots organizing efforts in Rhode Island have been directed toward improving maternal and infant health. Coalitions of consumer organizations, health care providers, and activists have achieved important legislative initiatives, such as health insurance for uninsured pregnant women and promotion of midwifery services. This article examines the processes involved in organizing for improved maternal and infant health care, the dynamics involved in achieving a particular outcome, and the ways in which grassroots mobilization can affect public policy and contribute toward improved maternal and infant health. PMID- 1930440 TI - Some thoughts on collaboration in perinatal research. PMID- 1930439 TI - Legislative strategies in Massachusetts and New York. PMID- 1930441 TI - The perinatal research agenda: whose priorities? PMID- 1930442 TI - Prenatal care and prematurity: is there an association in uncomplicated pregnancies? AB - A retrospective investigation examined patterns of use of prenatal care and pregnancy outcomes (low birthweight and preterm births) in 6176 pregnancies without antepartum medical complications. Prenatal care use patterns differed significantly by mother's age, marital status, race, education, method of payment, and gravidity. By controlling for these differences through a logistic regression procedure, results showed that prenatal care was associated with significant reductions in the number of infants who were delivered preterm or had low birthweight. Fewer very low-birthweight (less than 1500 g) infants were among the preterm infants delivered to mothers with prenatal care compared with women who received no prenatal care. These data suggest that significant improvements in pregnancy outcomes are seen among women who use prenatal care, and these benefits occur in the absence of antepartum complications. PMID- 1930443 TI - What are the benefits of prenatal care in uncomplicated pregnancy? PMID- 1930444 TI - A randomized study of two methods of teaching perineal massage: effects on practice rates, episiotomy rates, and lacerations. AB - This study examined the effects of two methods of teaching perineal massage on the rates of practice of perineal massage, of episiotomy, and of lacerations in primiparas at birth. Couples in 20 randomly selected sections of four prenatal class series received routine printed and verbal instruction and a 12-minute video demonstration of perineal massage, or only the routine printed and verbal instruction. Women reported their practice rates in daily diary records, which were mailed to the researcher weekly. Hospital records provided delivery data. Of the 83 women, 23 (28%) practiced perineal massage: 16 (35.6%) in the experimental group, 7 (18.4%) controls. Even though the rate of practice almost doubled among experimental group women, the videotape instruction method was statistically nonsignificant. Episiotomy and laceration rates were not affected by teaching method. More severe lacerations occurred among the experimental group; however, the control group had almost four times as many severe (21%) as minor (5.3%) lacerations. The experimental group had twice as many severe (28.9%) as minor (13.3%) lacerations. These results were also nonsignificant. PMID- 1930446 TI - Sheila Kitzinger's letter from England. PMID- 1930445 TI - Preterm birth prevention: an evaluation of programs in the United States. AB - During the last decade several programs were established to prevent the onset of preterm labor and facilitate its early identification and treatment. Although these prevention programs shared a similar goal, they varied in their primary outcome focus, target populations, study designs, and specific intervention components. Their initial reports were promising; however, subsequent evaluations of efforts in the United States produced mixed results. The current literature is suggestive of the benefits of programs to prevent preterm labor and delivery, but methodologic differences among them and deficiencies in the reported evaluations have rendered a final verdict equivocal. Many studies using historical or geographic controls found positive results, whereas randomized, controlled trials did not find a significant impact. Positive results were found in studies using low-risk populations, but investigations of high-risk patients noted little effect. Together with continued research on the factors that underlie the onset of labor, additional assessment of these programs and their individual intervention components appears to be necessary. PMID- 1930447 TI - Breastfeeding and fathers: illuminating the darker side. PMID- 1930448 TI - The most recent national cesarean and VBAC rates. PMID- 1930449 TI - [Oral amyloidosis. Concept, histopathology, clinical manifestations and treatment. Presentation of a clinical case]. AB - The definition and current classification of amyloidosis as well as the incidence, etiopathogenesis, pathology, clinical manifestations, specific diagnosis and prognosis and treatment of the disease are reviewed. A case of amyloidosis of the oral cavity without systemic involvement is reported. A 77 year-old woman suffered from multiple tumor masses in the mouth and presented with symptoms of impaired speech and ingestion. PMID- 1930450 TI - [Epidemiological study of inflammatory periapical cysts]. AB - We have realized an epidemiologic study of 467 inflammatory periapical cysts. We have valued: age, sex, radiographic size, localization, clinic, evolution time and morphologic aspects. Ware not agree with some authors about some morphologic description. PMID- 1930451 TI - [Dental education and preclinical procedures to develop indirect vision]. AB - The technological advance and the development of the odontologic profession, requires the gradual incorporation of more accurate psycho-motrice methods. The aim of this report is the presentation of the systems elaborated for the development of the students' and odontologists' psycho-motive skill. This report describes the method known as "reflection box", for the learning of indirect vision. In order to achieve a training, for the correct odontologic practice, in ergonomic positions that prevent skeleton-muscle disorders resulted from inadequate professional practices, exercises in two and three dimensions should be carried out with said box. PMID- 1930452 TI - [Oral lesions in a group of heroin addicts]. AB - Lesions of the oral mucous membrane are studied in 100 heroin dependent people compared with 100 control, other habits like smoking, alcohol ingesting and sexual oral practices are also taking in consideration. Salival flux and other salival characteristics are also analyzed. The heroin dependent people show significative increase in salival filament but this difference that's not exit of we also analyze in the lesions of lips, tongue, palate and vestibule in relation to controls. Nevertheless in the take into account only smokers and drinkers of both groups the only lesions significantly more frequent are those on the lips. PMID- 1930453 TI - [Complications of cervicofacial radiotherapy. Prevention, diagnosis and multidisciplinary treatment]. AB - This paper presents a review on the state of art about scientific knowledge on oral complications of head and neck radiotherapy, in an attempt to contribute for a better prevention, diagnosis and treatment. The authors also describe the protocols used on Instituto Portugues de Oncologia of Lisboa. PMID- 1930454 TI - [Analysis of the psychodynamic aspects of the dentist-patient relationship. 2. Regression of the patient]. AB - Authors analyse the regression phenomenon in the context odonto-stomatologist patient relationship, covering the study of transference, countertransference and the painful and anguish sensations. PMID- 1930455 TI - [A different approach to perceptive phenomena in 250 0-5-year old children]. AB - In this work there is a comparison between the different perceptions that a child can get from the dental instruments. The perception of dental instruments influences in a determinative way during dental attention. The sample consisted in the selection of 250 children whose ages ranges from 0 to 5 years. It was determined that age and experience influence in the perception of the objects as well as the different dental instruments used as variables. PMID- 1930456 TI - [Bonding of glass ionomer cement to dentin. An in vitro study]. AB - It's been studied "in vitro" the influence of the "Smear Layer" on the cement adhesion of the glass ionomer to the dentin. Using phosphoric acid at 37% and poliacrylic in the dentin during short periods of time, the adhesion between the cement and the dentin is improved because the Smear Layer is removed totally in the case of phosphoric acid and partially in the case of polyacrylic acid. PMID- 1930457 TI - [Removable partial denture. A variation on the gauge used in design]. AB - In this article we describe a modification of the gauge of the surveyor in such a way that we can measure the height of the retention arms' slide area over the abutment teeth, in order to obtain the same height in the reciprocal arm slide area to avoid the jiggle movements of the abutment teeth during the removal and insertion. PMID- 1930458 TI - [Importance of color in dental materials]. PMID- 1930459 TI - [Our experience in treating complete incisor-coronal fractures, using corono radicular posts and microfilled composites]. PMID- 1930460 TI - [Functional lymphocyte tests in periodontal disease]. PMID- 1930461 TI - [Metal alloys used for dentures]. PMID- 1930462 TI - [Pilomatrixoma. Review of 179 cases]. AB - We introduce a study about 179 cases of Pilomatrixioma, registered in the archives from General Hospital "Vall d'Hebron" of Barcelona between 1972-1988. Tumour of pediatric presentation, about 502 of cases have been observed in young people under 20 years, being both sexes almost equally affected percentually. About 75% of cases appear a a a single tumour smaller than 15 mm of diameter. Multiple presentation is observed only in the 2.8 of cases. A bit more than the 50% of cases are located in the head and the neck, usually in the preauricular region. Next follow upper extremities (27%), lower extremities (11%), and the rest of the body (6.7%). Recidivation appear only in the 0.55% of cases. PMID- 1930463 TI - [Nontumoral pathology of the tongue]. PMID- 1930464 TI - [Clinical study of a microfilled posterior composite. Results after 5 years]. PMID- 1930465 TI - [Studies on the benefits of using assistants in the dental clinic]. AB - We've analysed the systematization in odontological assistance in fifty dental clinics placed in our area. The variables examined: Working hours per day, working days per week, weeks of holiday per year, patients treated per year, number of dental assistants, number of operatories room. We've calculated a series of formulas and compared them with ideal values. PMID- 1930466 TI - [Complete dental impressions. Recommended technique as a function of the prognosis of the inserted denture]. PMID- 1930467 TI - [Cyclosporin induced gingival hyperplasia]. AB - Cyclosporine is a strong immunosuppressive drug, which is used specially in transplantation patients, however in some cases, like others medicines it causes, gingival overgrowth. In the present article we present five transplantations patients, (one of liver, and four of kidney), whom have taken this drug since more than a year at different dosages. One of them, never has presented overgrowth, whereas the rest cases have needed this specific periodontal treatment to solve hyperplasy. After this work, we don't find clear relationship between drug dosage-age-effect over tissues. PMID- 1930468 TI - [Evaluation of the rate of tooth eruption]. PMID- 1930469 TI - Dermatophyte feet infection among students enrolled in swimming courses at a university pool. AB - The aim of this study was to determine the prevalence of dermatophyte feet infection among students enrolled in swimming courses at a university swimming pool. Tinea pedis infection was determined on two occasions. The first study took place on the first day of classes and the second on day twelve of swimming lessons. Culture and KOH examination of the interdigital skin scrapings of the left foot showed superficial foot infection with dermatophytes or Candida albicans in 13.2% of the students (11/83) in the first study, and in 22.2% of the students (16/72) in the second study. The most common agent of tinea pedis in the first study was Trichophyton rubrum (82%), infections by T. mentagrophytes (9%) and Epidermophyton floccosum (9%) were less common. At that time, no dermatophyte was recovered from any of 30 floor samples taken from the bathroom and pool facilities. In the second study the following dermatophytes were isolated from the student's feet: T. mentagrophytes (70.6%), T. rubrum (17.6%) and Candida albicans (11.8%). On this occasion T. mentagrophytes was recovered from 5 out of 30 floor samples. It is possible that the frequency of the use of the pool facilities may influence the prevalence of tinea pedis as well as the etiological agent involved in this disease. PMID- 1930470 TI - Elevated ALT activity in volunteer blood donors. AB - By far, the most common cause of post-transfusion hepatitis (PTH) is infection with the non-A, non-B hepatitis (NANB) virus. Until very recently, no specific laboratory test existed to detect the presence of this virus in donated blood. However, a correlation has been established between high donor ALT (formerly SGPT) and recipient PTH and between positive donor core antibody and recipient PTH. To lower the current high incidence of NANB-induced PTH, in 1986, the American Association of Blood Banks (AABB) recommended testing for these PTH associated "surrogate" markers on all donated units of blood. Accordingly, testing for Hepatitis B core antibody and for ALT activity were implemented. This practice produced large amounts of data on populational ALT activity levels and core antibody positivity. The ALT activity of 3108 healthy volunteer blood donors as recorded in the donor files of the Hospital Universitario Ramon Ruiz Arnau Blood Bank were analyzed retrospectively to determine what the local normal ALT activity was. It was determined that the average ALT was 35.91 units/liter. This average is much higher than averages reported by other blood banks in the literature. Possible causes of the high local ALT activity levels are discussed. PMID- 1930471 TI - Increased alanine aminotransferase (ALT-SGPT) activity in Puerto Rican blood donors. AB - Data was obtained from 4189 volunteer blood donation records in two hospital based blood banks in Puerto Rico to determine whether Hispanics have higher serum alanine aminotransferase (ALT-SGPT) activity than donors from other racial-ethnic groups. The overall mean value of ALT-SGPT in the study population was 36.84 u/l (range 1-910, standard deviation 37.8). When the logarithm of ALT-SGPT (log ALT) was calculated for all subjects, the overall, mean for log ALT was 1.47 (range 1 2.96, standard deviation 0.27). Analysis of each blood bank's donation records at two different time periods showed a consistently high ALT-SGPT activity even when donations positive for hepatitis B surface antigen or other serologic markers were excluded. Though the causal factor of this finding is not clear, non infectious environmental such as alcohol consumption should be considered as a probable explanation. PMID- 1930472 TI - The use of autologous blood transfusions in pediatric orthopaedic surgery. AB - This study reviews the medical records of 29 patients that were submitted to 29 spinal fusion procedures with the purpose to evaluates the efficacy of using predeposited autologous blood transfusions to replace operative blood loss. The patients age ranged from 8 to 25 years. Each patient was started on oral iron supplement as soon as surgery was scheduled. The phlebotomies were performed at the American Red Cross Blood Services Puerto Rico Chapter. Blood was drawn 1 unit every 6 days if the hematocrit was above 34%. The last phlebotomy was performed at least 7 days before surgery. The average amount of blood donated was 3.17 units (1,427 ml). The whole blood was stored using the adenine saline solution (ADSOL) as preservative for as long as 35 days. The average preoperative hematocrit value was 35%. In 89% of the cases only autologous blood was transfused. In the rest of the cases family donated homologous blood was required. The use of pre deposited autologous blood for replacement of operative blood loss has proven to be a safe, easy and well accepted method for the pediatric age patients. It also reduced the need for homologous blood and helps to increase the blood reserve at banks. PMID- 1930474 TI - [Rafael G. Sorrentino, MD. 1916-1991. In memoriam]. PMID- 1930473 TI - [Cancer of the prostate. Methods of initial diagnosis]. AB - We herein describe teh diagnostic methods available for the screening of Carcinoma of the Prostate. As recommended by the NCI. Rectal Digital Exam (RDE) and Prostatic Specific Antigens (PSA) are the usual screening methods to be use. Depending on their results, we proceed with Transrectal Prostatic Ultrasound with or without biopsy. PMID- 1930475 TI - Cancer statistics, 1991. PMID- 1930476 TI - [Cancer incidence by municipalities in Puerto Rico]. AB - This study consist of the trends of those malignant tumours in Puerto Rico diagnosed 1960 to 1988 that we considered more related with some environmental factors. For this purpose 160,288 cancer cases analyzed included 16,286 of squamous and basal cell carcinomas of the skin diagnosed from 1950 up to 1975 only. We have darkened in the map and mentioned below in this summary those municipalities with incidence greater than Puerto Rico's average. PMID- 1930477 TI - [Environmental epidemiology of cancer in Puerto Rico: 1987-1988]. AB - An epidemiological analysis on cancer was run for the years 1987 and 1988 and for each municipal jurisdiction in Puerto Rico. Areas of pronounced incidence were examined on the basis of possible environmental cause-and-effect relationships. The cancer data examined were based on first diagnoses for cancer of all types, respiratory cancer and leukemia. The municipality of Catano was salient in most incidences. Catano lies downwind from the largest metropolitan urban center in Puerto Rico (population density 9,559 inhabitants per square mile), from the largest number of industries for the island, from past and present uncontrolled non-compliance air emissions, from the largest number of vehicles, and is surrounded by wetlands. Also salient were other municipalities of historical or current heavy industrial emission activity with lenient or non-existent environmental controls. PMID- 1930478 TI - [Successes and failures of epidemiologic methods to study cancer etiology]. PMID- 1930479 TI - [Experience with the cancer registry in Puerto Rico]. PMID- 1930480 TI - The Puerto Rico and New York State tumor registries: problems associated with the use of cancer incidence data in migrant studies. AB - This paper discusses specific problems pertaining to compatibility of data between the Puerto Rico and New York State tumor registries, which is applicable to other studies comparing cancer incidence rates from two distinct tumor registries. Discrepancies in the data between the two tumor registries were due to differences in quality control, under and overreporting of cancer cases, reliability indicators, and case criteria. A study comparing stomach cancer incidence rates between Puerto Rico and Puerto Rican migrants to New York City provided the foundation for this investigation. PMID- 1930481 TI - Fat and breast cancer: a mini-review of experimental data on rodents. AB - High dietary fat has been consistently linked to breast cancer in epidemiological and experimental studies. This communication reviews the possible mechanisms involved in this relationship. Also we review the effects of different fats on breast cancer growth in recent experimental studies. PMID- 1930483 TI - [Cancer, a disease that can be prevented, controlled and cured. Truths about cancer treatment]. PMID- 1930482 TI - Nutrition and cancer: American Cancer Society guidelines, programs, and initiatives. PMID- 1930484 TI - [Which are the protective factors against cancer?]. PMID- 1930485 TI - [To cite and be cited]. PMID- 1930486 TI - [Early detection of cisplatin-induced ototoxicity using evoked otoacoustic emissions]. AB - In a prospective study we examined the effects of cisplatinum on the amplitude of evoked otoacoustic emissions and thus on cochlear micromechanics. 29 patients were examined. Amplitude changes of click-evoked otoacoustic emissions were compared with the threshold of pure-tone audiometry. We observed that an amplitude loss of otoacoustic emissions is a sensitive tool for the early detection of cochlear dysfunction. "Minimal lesions" of the inner ear were observed at an earlier stage during the current therapy than when using conventional audiometry. Measuring and recording otoacoustic emissions enables to diagnose beginning cochlear lesions caused by ototoxic drugs before they become clinically manifest. PMID- 1930487 TI - [The development of endogenous inner ear hearing loss due to occupational noise exposure]. AB - Pure tone audiograms of 80 workmen with preexisting endogenous cochlear hearing loss were investigated over an average of 16 years (range 10 to 26) of occupational exposure to noise. Further hearing deterioration was moderate in the majority of cases more severe hearing losses more often affected the low tone range. The pure tone threshold 0.25 to 8 kHz remained unaltered in at least one ear in 24% of cases, in the high tone range 3 to 6 kHz in 51%. The average hearing loss was least at 3 kHz, followed by 4 kHz. The average hearing loss was somewhat greater in the initially better hearing ear. Differences between the two sides mostly developed in the high and the low tone region of trough-shaped thresholds, and in the low tone region of sloping thresholds. Hearing losses were greater when preexisting impairment did not exceed 30 dB HL than in preexisting damage over 30 dB HL. The average hearing losses for 0.5, 1, 2, 3 and 4 kHz were all lower than the respective average values for noise-induced hearing loss. Thus there was no evidence of increased noise susceptibility in endogenous cochlear hearing loss, either in comparison with controls or in a comparison of the sides or frequency ranges. PMID- 1930488 TI - [Tube function in sudden hearing loss]. AB - The function of the Eustachian tube was assessed in 50 patients suffering from sudden hearing loss, using the pressure chamber impedance method. We investigated the existence of a relationship between sudden hearing loss and the occurrence of a patulous tube. We could not observe more patulous tubes in patients with sudden hearing loss compared to a control group with healthy ears. We registered the parameters "tissue resistance pressure" and "tubal opening pressure", both characterising the passive qualities of the Eustachian tube. There was no indication of a facilitated passive tubal opening nor a tendency to a patulous tube among our patients. Statistical evaluation of these parameters showed no significantly different tubal function on comparing the right and the left ear, as well as the ear affected by sudden hearing loss and the healthy ear. We conclude that there is no relationship between sudden hearing loss and patulous tube. PMID- 1930489 TI - [Results of multistep oxygen therapy in the treatment of sudden hearing loss]. AB - Oxygen multistep therapy (von Ardenne) was applied in 28 patients suffering from an idiopathic sudden hearing loss. The oxygen therapy consisted of a multistep short procedure, each of which lasted for 15 minutes. The results of our study were evaluated by means of standardised statistics confirming the effectiveness and even the superiority of the oxygen multistep therapy in comparison with any other treatment, and also in view of the spontaneous remission rate in cases of sudden hearing loss. PMID- 1930490 TI - [Danger areas of the posterior nasal base: anatomical, histological and endoscopic findings]. AB - In 52 cadaveric half-heads and endoscopic sphenoethmoidectomy was performed. Subsequently an anatomical preparation with registration of specific data like bulging of the optic canal, thickness of the bony wall covering the optic nerve and the internal carotid artery was achieved, followed by histological sections in specially selected cases. Thus the two key areas of major surgical hazard in the posterior rhinobasis could be clearly demonstrated: the immediate topographic relation of the optic canal and the internal carotid artery to the lateral wall of the sphenoid sinus and the cells of the posterior ethmoid, respectively. Onodi cells of varying degrees were found in 42% of all cases. The thickness of bony wall over the maximum bulging of the optic canal averaged 0.28 mm. Bony dehiscences could be demonstrated in 12% of the cases. The technique of data acquisition, the anatomical and histological findings as well as their clinical and surgical relevance are discussed. PMID- 1930491 TI - [Possibilities of treating nasal turbinates in the framework of endonasal microsurgery]. AB - Pathologic alterations of the turbinates are common in infectious diseases of the nose and paranasal sinuses. Over 300 patients were treated for paranasal sinuses disease from 1986 to 1989 by endonasal microsurgery. One-third of the patients were found intraoperatively to have alterations of the middle and inferior turbinate causing obstruction and functional disorders of the nose and sinuses. Our concept comprises a step-by-step microsurgical approach to the turbinates. The technique and the results are presented. PMID- 1930492 TI - [Video-fluoroscopy in a graduated diagnostic program in oral cavity and pharyngeal carcinoma]. AB - The role of videofluoroscopy in the preoperative evaluation of 38 carcinomas of the oral cavity and oro-/hypopharynx is described. The analysis compared videofluoroscopy with CT and endoscopic assessment, since videofluoroscopy is the only imaging method that can record dynamic motility changes during deglutition. The intraluminal part of the tumour is well visualised by high contrast resolution of the pharyngeal mucosa. The extent of tumorous infiltration can be evaluated via indirect criteria such as leaking, vallecular asymmetry, impaired epiglottic movement with insufficient vestibular closure, pharyngeal wall rigidity, and laryngeal aspiration. Carcinoma of the oral cavity and piriform sinus often do not cause functional swallowing impairments that can be detected by videofluoroscopy. However, in case of carcinoma at the base of the tongue region as the major driving force in bolus movement, videofluoroscopic assessment yields important additional information supplementing CT and endoscopic findings. PMID- 1930493 TI - [Ultrasonic diagnosis of the tonsillar region]. AB - From 1989 to 1991, 126 tonsils were prospectively studied in cadavers, volunteers and patients by B-scan ultrasonography. The transducer was positioned just medial of the mandibular angle. The submandibular gland, M. digastricus, M. stylohyoideus and the tongue proved to be suitable landmarks. Normal and chronically inflamed tonsils both presented as oval structures with weak echos. Peritonsillar abscess could not be sonographically defined in 13/15 cases. Squamous cell carcinoma presented with random echos and indistinct borders. Infiltration of the base of the tongue could be safely confirmed. PMID- 1930494 TI - [Proton spin tomography in HIV 1-induced diseases in head and neck region]. AB - Most HIV-infected patients present with associated diseases (inflammations, hyperplastic disorders of the lymphatic tissue and malignancies) in the head and neck region. Speculum, endoscopy, ultrasound and computed tomography are important tools in the diagnostic management of HIV presentations. Moreover, MR is known to be an excellent technique especially in the evaluation of soft tissue disorders. -A prospective study of 23 out of 161 HIV-seropositive patients was performed to determine the efficiency of magnetic resonance imaging in HIV related disorders. T1- and T2-sequences, as well as the contrast medium uptake (Gd-DTPA), presentation in three planes and the morphology of the tissue were useful parameters to distinguish the different HIV-related diseases (lymphatic hyperplasia, inflammation, Kaposi's sarcoma, Hodgkin's und Non-Hodgkin lymphoma, lymphoepithelial cysts and carcinoma) in most cases even prior to histological examination. -MR proved to be a significant non-invasive diagnostic tool especially in HIV-associated soft tissue disorders in the head and neck. PMID- 1930495 TI - [Functional and electromyographic long-term results following primary microsurgical repair of the recurrent laryngeal nerve]. AB - Six patients with unilateral recurrent nerve paralysis underwent phoniatric follow-up after neurolysis or primary microsurgical repair of the recurrent laryngeal nerve. Four patients were controlled by electromyography of the vocal muscle 14 to 80 months post-operatively. In six patients the paralyzed vocal cords were in median to paramedian position with sustained muscle tonus. Phoniatric parameters were found to be close to the average range in healthy persons. EMG findings indicated degenerative neurogenous paralyses in two patients, signs of reinnervation in another. In one case biphasic action potentials could be recorded. PMID- 1930496 TI - [Coincidental appearance of laryngocele and laryngeal carcinoma]. AB - The authors present a case of a 54-year-old male patient suffering from a laryngocele with concomitant laryngeal cancer. The patient had a three-month history of hoarseness. The clinical examination as well as the endoscopic evaluation did not reveal any signs of malignancy inside the larynx. MR imaging, however, showed an endolaryngeal cystic process surrounded by a soft tissue mass. Resection of the lesion revealed the concomitant occurrence of both laryngocele and laryngeal carcinoma. Etiology, symptoms, diagnostic management and differential diagnosis are presented and discussed according to the relevant literature. PMID- 1930497 TI - [Amalgam tattoo--an important differential diagnosis from malignant melanoma of the mouth mucosa]. AB - Amalgam tattoos develop as an amalgam deposit often as a result of continuous contact between an amalgam filling and the gingiva or amalgam fragments embedded in the oral tissue during dental filling or surgical operations. Sometimes fragments of amalgam restorations are broken off during extraction and embed in the adjacent soft tissue. In our case a small piece of amalgam had broken off during an extraction after retrograde filling up this tooth some years before following a resection of the dental root. Embedded in the depth of the bony resection cavity the piece of amalgam had produced the amalgam tattoo 13 years later. PMID- 1930498 TI - [A new ventilation technique in partial larynx resection]. PMID- 1930499 TI - Gastric emptying following Colles' fracture. AB - There are few complications associated with intravenous regional anaesthesia but convulsions with loss of consciousness induced by local anaesthetic toxicity may result in pulmonary aspiration. In many hospitals, patients are fasted prior to the procedure although such a delay would be of little value if gastric emptying was inhibited following painful injury. Utilizing the kinetics of paracetamol absorption, we investigated the rate of gastric emptying in patients sustaining a Colles' fracture within the previous 4 h. Post-manipulation control values were obtained at their first out-patient attendance. There was no statistically significant difference in the rate of gastric emptying. Since gastric emptying is not delayed by a recent Colles' fracture, the simple precaution of fasting patients prior to intravenous regional anaesthesia should reduce the risk of pulmonary aspiration. PMID- 1930500 TI - The management of upper gastrointestinal haemorrhage in a tropical country. PMID- 1930501 TI - When to stop resuscitation--the significance of cuff blood pressure. AB - Fifteen consecutive patients who had been resuscitated from cardiac arrest and transferred immediately to an Intensive Care Unit were studied. Measurements of intraarterial pressure, cardiac output and systemic vascular resistance demonstrate that 'cuff' blood pressure may not always be related to intraarterial pressure or cardiac output and cannot be used for diagnostic, therapeutic, or prognostic purposes. Following resuscitation, a palpable pulse was present in each of these patients, but did not correlate with adequacy of cardiac output. Too often we hear during a cardiac arrest the question 'Does the patient have an output?', when we should really be asking 'Does the patient have a pulse?'. The palpation of a pulse is a simple and important indication of spontaneous cardiac activity. However cardiac output must be measured and it's adequacy cannot be inferred from this basic clinical measurement. PMID- 1930502 TI - The video-recorder in the accident and emergency department. PMID- 1930503 TI - Do ambulance crews triage trauma patients? AB - OBJECTIVE: To determine whether ambulance crew triage trauma patients appropriately. DESIGN: A retrospective descriptive study. SETTINGS: Cornwall County Ambulance Service. VARIABLES STUDIED: On-scene times, injury severity, establishment of intravenous infusion and time from scene to A&E department. SUBJECTS: Patients with compound fracture of the lower limb taken to Truro Accident and Emergency department. OUTCOME MEASURES: Ambulance service on-scene times and mission times. RESULTS: Ambulance crew do not appear to be triaging patients appropriately. Excessive time is being spent on pre-hospital stabilization. Delivery of patients to a casualty department is delayed. CONCLUSION: At present the activities of paramedics are poorly supervised, and pre-hospital management by paramedics may be jeopardizing patient care. PMID- 1930504 TI - An improved method of communication between computerized accident and emergency departments and general practitioners. AB - This new system of communication sends the data on four sticky labels (Fig. 1), one of which can be permanently left in the patients folder without taking up too much space. Further details can be obtained by telephoning the A&E department and quoting the A&E number on the sticky label. PMID- 1930505 TI - Unscheduled return visits by patients to the accident and emergency department. AB - To determine why patients reattend an A&E department we surveyed 235 patients who returned unscheduled in a one-month period. Sixty-two per cent returned because of persistent symptoms. Sixty-three per cent presented within a week of their initial visit. Only 32% had attempted to see their GP. Thirty-five per cent of all patients claimed that A&E staff had advised them to return if they had problems. Half of the patients did not require treatment and 61% were discharged home. Twenty-one patients had pathology that had been missed on their first visit. Better patient education may minimize misuse of the service allowing better care for those who need it. PMID- 1930506 TI - Ocular trauma: one in the eye for safety glasses. AB - Over a 3-month-period, a prospective study was performed on patients presenting with eye injuries to an Accident and Emergency Department. Two hundred and forty five patients presented, representing 3.7% of total new patients seen in that period. The majority of injuries (81%) occurred in the workplace, injuries associated with grinding (32%) being the commonest. Retained foreign body (52%) was the most common injury. Eye protection was provided in 64% of cases, but only used in 48.5% of these. Seventy-eight per cent of cases were discharged without follow-up. The use of goggles appeared to provide the greatest degree of protection. PMID- 1930507 TI - Teaching trauma management in the accident and emergency department. AB - Since their introduction into the United Kingdom, Advanced Trauma Life Support Courses (ATLS) have preferentially offered places to Consultants and Senior Registrars. It is usual, however, for the initial resuscitation of the seriously injured patient to be performed by relatively inexperienced junior staff. It is incumbent upon those medical staff who are ATLS providers or instructors to design local courses, based upon ATLS principals, to train their junior staff in a structured approach to managing these patients. We describe one such local course which may serve as a model for others. PMID- 1930508 TI - How do nurses working in hospital accident and emergency departments perceive local general practitioners? A study in six English hospitals. AB - One hundred and forty-three Accident and Emergency nurses working in six departments in contrasting districts of England completed questionnaires about their perception of local general practice. Much of general practice was perceived as being performed unsatisfactorily. Out-of-hours accessibility, caring for patients with 'difficult' or psychosocial problems, advising on health service usage, and minor surgery and first aid were all thought to be performed particularly badly. In addition, there was considerable inter-district variation with the views expressed in inner London being especially negative. To some extent these views may reflect real short-comings in general practice, but they are likely to be coloured by the disproportionate experience A&E departments inevitably have of patients who are dissatisfied in some way with their GP service. In addition, other factors such as departmental 'culture' and the separation that exists between hospital and community health professionals may have an important influence. The effect such negative perceptions have on the relationship between A&E departments and general practitioners, and the quality of care provided to patients attending A&W with primary care problems are discussed. PMID- 1930509 TI - Trauma and Munchausen's syndrome. AB - A case of Munchausen's syndrome presenting as trauma is reported. Clinician awareness is the most important lesson from such a patient. The condition represents a distinct entity from deliberate self-harm, but it is suggested that psychiatric referral is mandatory. PMID- 1930510 TI - The delayed presentation of limb fractures in A&E departments. PMID- 1930511 TI - The respiratory rate. PMID- 1930512 TI - Use of retrograde urethrography in the resuscitation room. PMID- 1930513 TI - Changes in moral reasoning during medical school. PMID- 1930514 TI - Class ranking models for deans' letters and their psychometric evaluation. PMID- 1930515 TI - Admission interview ratings: relationship to applicant academic and demographic variables and interviewer characteristics. PMID- 1930516 TI - Accuracy of surgery clerkship performance raters. PMID- 1930517 TI - Interrelationships between knowledge and performance-based testing in a surgery clerkship. PMID- 1930518 TI - Can trait anxiety, grades, and test scores measured prior to medical school matriculation predict clerkship performance? PMID- 1930519 TI - Is test security an issue in a multistation clinical assessment? A preliminary study. PMID- 1930520 TI - The interaction of student gender and standardized-patient gender on a performance-based examination of clinical competence. PMID- 1930521 TI - The assessment of interpersonal skills using standardized patients. PMID- 1930522 TI - Using unannounced simulated patients to evaluate sexual risk assessment and risk reduction skills of practicing physicians. PMID- 1930523 TI - How medical school shapes students' orientation to patients' psychological problems. PMID- 1930525 TI - The impact of medical school debt on postgraduate career and lifestyle. PMID- 1930524 TI - A comparison of short-answer and extended-matching question scores in an objective structured clinical exam. PMID- 1930526 TI - Clinician involvement in practice analysis and change in three teaching hospitals. PMID- 1930527 TI - Demonstrating the efficacy of the patient logbook as a program evaluation tool. PMID- 1930528 TI - An inquiry into the education of the surgical clinical investigator. PMID- 1930529 TI - An assessment of the impact of ambulatory care education of third-year medical students. PMID- 1930530 TI - Trends in the medical knowledge and clinical competence of graduates of internal medicine residency training programs. PMID- 1930531 TI - The use of standardized patients to evaluate the spoken-English proficiency of foreign medical graduates. PMID- 1930532 TI - Sequential testing with a performance-based examination using standardized patients. PMID- 1930533 TI - Validating an objective structured clinical examination (OSCE) as a method for selecting foreign medical graduates for a pre-internship program. PMID- 1930534 TI - Validity of NBME Part I and Part II scores in prediction of Part III performance. PMID- 1930535 TI - Semantic structures and diagnostic thinking of experts and novices. PMID- 1930536 TI - Search path mapping: a versatile approach for visualizing problem-solving behavior. PMID- 1930537 TI - Framing bias among expert and novice physicians. PMID- 1930538 TI - A case study of student-directed discussion in four problem-based tutorial groups. PMID- 1930539 TI - The effect of curriculum era on NBME Part I outcomes in a problem-based versus a traditional curriculum track. PMID- 1930540 TI - Offices of research in medical education: "what have you guys ever done anyway?". PMID- 1930541 TI - High-resolution three-dimensional images from confocal scanning laser microscopy. Quantitative study and mathematical correction of the effects from bleaching and fluorescence attenuation in depth. AB - Three-dimensional images can be assembled by piling up consecutive confocal fluorescent images obtained by confocal scanning laser microscopy. The present work was based on three-dimensional (50-microns-deep) images at high (x, y) resolution obtained with an MRC-500 after en bloc staining of thick slices of rat liver by chromomycin A3 for nuclear DNA. The results of studies on bleaching, fluorescence excitation and emission intensities at various depths of histologic preparations are described. These effects could be evaluated separately by acquiring piled-up ("brick-stepping") and non-piled-up ("side-stepping") (x, y) images at consecutive depths and also (x, z) images. Empirical equations allowed the fitting of experimental plots of bleaching versus time, at different laser intensities and at different depths, and of fluorescence emission intensity versus depth. The main conclusions were that under our experimental conditions: (1) there was no attenuation by depth of the fluorochrome penetration, (2) there was no attenuation of the exciting beam intensity up to at least 50 microns deep, (3) there was an attenuation of the fluorescence emission intensity by depth, (4) bleaching happened equally on all planes above and below any confocal plane being studied, and (5) the fluorescence bleaching half-life was independent of depth. A mathematical correction scheme designed to compensate for bleaching and for attenuation of fluorescence emission in depth is presented. This correction is required for obtaining three-dimensional images of better quality, for optimal three-dimensional image segmentation and for any quantitative analysis based upon voxel-discretized emission intensities (gray levels)--e.g., estimating, by confocal image cytometry, textural chromatin parameters and nuclear DNA amounts. PMID- 1930542 TI - Determination of nuclear DNA content and hormone receptors in breast cancer by the CAS 100 cell analysis system as related to morphologic grade and biochemical results. AB - Quantitative DNA analysis by the CAS 100 Cell Analysis System was performed on 120 cases of primary breast carcinoma using touch preparations from fresh biopsy specimens in 110 cases and archival, restrained fine needle preparations in 10 cases. Fifteen cases of metastatic breast carcinoma and 15 cases of benign breast lesions were also analyzed. Overall, 76.7% of the carcinomas examined were aneuploid, with most DNA indices between 1.6 and 2.0. DNA anomalies were strongly related to nuclear atypia but not to structural differentiation. The hormone receptor content, when compared with DNA data and morphologic features, emerged as a biologically independent factor. Agreement between quantitative immunocytochemical assay (QICA) using the CAS system and traditional dextran coated charcoal assay (DCCA) in discriminating positive and negative status for estrogen receptors and progesterone receptors was 86% and 82%, respectively. Marked variations, however, occurred in the numerical values. Considering the advantages of QICA and the importance of tumor heterogeneity in particular, the use of traditional DCCA as the reference technique and only guide for therapy no longer seems justified. PMID- 1930543 TI - Data on automated cytology systems as submitted by their developers. PMID- 1930544 TI - [Emergency systems in Styria]. AB - Since 1980 the emergency systems of Graz consisting of two emergency ambulances, two large space emergency ambulances and an emergency helicopter with a range of more than 50 km has been sufficient. The two helicopters cover nearly 100% of the Federal State of Styria but regarding the ground emergency systems there are still insufficiently covered areas in many parts of our state. The ground emergency systems can only be supported but they cannot be replaced by the helicopter. We hope to have an emergency ambulance at every peripheral hospital in the future. Now an efficient emergency system exists in Graz since the first public lecture on first aid and reanimation has been held 175 years ago. The missing link of a well functioning rescue chain is a well trained lay assistant whose level of training regarding "Life Saving Emergency Measures" constantly has to be refreshed. Only with a sufficient number of trained lay assistants it is possible to save all those who have a real chance of successful reanimation. PMID- 1930546 TI - [Epinephrine and norepinephrine release immediately following acute cranio cerebral trauma and the resulting metabolic changes]. AB - Severe head injury leads to typical cardiocirculatory and metabolic changes by massive release of catecholamines. However, in the literature no data on these disturbances are available in humans in the preclinical phase. Therefore we measured in 34 head injured patients at the site of the accident and after hospital admission the degree of unconsciousness (Glasgow-Coma-Scale), blood pressure, heart rate, catecholamines, free fatty acids, electrolytes, lactate and blood sugar. Immediately after trauma a close correlation was found between the Glasgow-Coma-Score and the levels of adrenaline and noradrenaline, respectively (R = 0.64; R = 59). A closer relationship was found between Glasgow-Coma-Scale and the extent of hypopotassemia. However, no correlation existed between the degree of loss of consciousness and haemodynamic parameters, electrolytes, blood sugar and lactate. On hospital admission the extent of hypopotassemia showed a close relationship to the degree of excreted catecholamines at the site of accident. Patients intubated and ventilated at the scene showed remarkably lower catecholamine levels at the time of admission. PMID- 1930545 TI - [Opioid peptides in hemorrhagic shock]. AB - Regarding the treatment of vitally endangered intensive care patients the neuroendocrine regulation of the post-aggression metabolism is important. The role of opioid peptides in this system is investigated in the animal experiment "Haemorrhagic Shock in the Dog". It was shown that the opioid peptide beta endorphin and metenkephalin rise grossly in connection with pathological and endocrinological alterations in shock. Based on the literature the role of increased concentration of opioids in haemorrhagic shock is discussed and conclusions for therapeutic measures are presented. PMID- 1930547 TI - [Acute methanol poisoning--a review and a case report]. AB - Acute methanol intoxications are infrequent among accidental or suicidal intoxications today. The characteristic findings are illustrated by a review. Mainly, the methanol metabolites formaldehyde and formic acid are of toxicologic importance and cause the dominant central nervous and ocular symptoms. The principal therapeutic procedures include gastric lavage, induced vomiting, titrated correction of acidosis with sodium bicarbonate, administration of ethanol, folic acid and, especially, the secondary detoxication with peritoneal- or better--haemodialysis. The therapeutic measures must be started quickly and carried out consequently to improve the prognosis of methanol intoxication and to decrease the frequency of serious late complications like ophthalmologic and neurologic lesions. Our own medical management is described by a case report treated successfully. PMID- 1930548 TI - [The risk of infection in patients with long-term epidural catheters]. AB - In 16 pain patients with carcinoma with a total of 896 days of epidural catheter usage, one hospitalized patient developed meningitis. No general infection occurred among the outpatients. The benefit/risk ratio, satisfactory pain relief on one hand and risk of infection on the other, clearly demonstrated the advantage of long-term epidural catheter treatment in our patients, in particular in outpatients. Careful hygienic handling is essential. PMID- 1930550 TI - [The spirographic determination of O2 consumption during mechanical ventilation]. AB - A spirographic method to determine the oxygen consumption during artificial ventilation is described. In comparison with experimentally quoted VO2-values the mean relative error was less than 5%. The accuracy is more exact in higher inspiratory oxygen fractions. Therefore this method can be used for reference measurements. PMID- 1930549 TI - [A new method of determining the oxygen consumption of ventilated patients]. AB - A new method to determine the oxygen consumption in ventilated patients is described. The principle is based on application of the linear pressure slope from breathing pressure during lung closure (15 s with a maximum airway pressure of 10-15 mbar). This technique was compared with a modified spirographic method. In 11 patients and 18 observations we found the following results VO2SP = 36.573 ml/min + 0.887.VO2P1 (VO2SP: oxygen consumption with spirography, VO2P1: oxygen consumption with lung closure). The correlation coefficient was r = 0.9148. PMID- 1930551 TI - Diuretic agents related to indapamide. IV--Synthesis and pharmacological activity of N-(4-chloro-3-sulfamoylbenzamido)-methyl-phenyl-pyrrolidines and N1-(4-chloro 3-sulfamoylbenzoyl)-N2-aryl- or aralkyl-alkyl-hydrazines. AB - A series of N(4-chloro-3-sulfamoylbenzamido) derivatives (6 a-c, 10, 11, 12), structurally related to indapamide and isoindapamide, were synthesized and tested for their diuretic and saluretic activity. In addition, the antihypertensive activity of the most interesting term trans 6a was studied on spontaneously hypertensive rats. All tested compounds with the exception of 10 showed diuretic activity comparable to or higher (trans 6 a) than that of indapamide, taken as reference drug. The antihypertensive activity of trans 6 a was comparable to that of indapamide in potency, but its onset of action was slower. PMID- 1930552 TI - Synthesis and biological evaluation of new muscarinic receptor antagonists bearing cyclic amidines as cationic heads. AB - Two classes of compounds, bearing a cyclic amidino moiety instead of the tertiary amino group of the classical antimuscarinic drugs like hexahydrodifenidol 3 were synthesized. Affinities (KD) for the three pharmacologically defined M1, M2 and M3 mAChR subtypes were measured in radioligand binding assays and in functional in vitro studies (KB) in guinea pig ileum and left atrium. The results showed that the replacement of the tertiary amino group in structural analogues of 3 with a cyclic amidino moiety afforded potent antimuscarinic compounds. The selectivity shown for smooth muscle preparations suggests their usefulness as antispasmodics. PMID- 1930553 TI - Enzymatic synthesis of ampicillin: a chemometric optimization. AB - Statistical methods of optimization were applied to the enzymatic semisynthesis of ampicillin catalyzed by penicillin acylase. Since the traditional approach fails in determining both the presence of interactions between the variables and their magnitude, the reaction was reconsidered by means of chemometric techniques. In this work we determined the interaction between temperature and pH for the first time. PMID- 1930554 TI - Studies on 8-methoxypsoralen tolbutamide interactions in vitro and in vivo. AB - The present study aimed at characterizing the influence of tolbutamide on the distribution of 8-methoxypsoralen (8-MOP) in mouse serum and organs. Experiments performed in vitro clearly showed that tolbutamide causes competitive displacement of 8-MOP from its binding sites on human serum albumin. Similarly, the amount of labelled compound(s) bound in serum after oral administration of 3H 8-MOP to mice was significantly reduced when tolbutamide was given by the same route. The quantitative distribution of radioactivity from 3H-8-MOP in mouse tissues varied according to organ (liver, intestine, skin, etc.,), and was maximum in the organs of elimination. In all the organs studied, the administration of tolbutamide 2 hours after that of 3H-8-MOP caused a dose dependent reduction of the radioactive compound(s) present in tissues, suggesting that tolbutamide may accelerate the excretion of 8-MOP and/or its metabolites from the body. PMID- 1930555 TI - Chlorocoulometric determination of hydrocortisone and hydrocortisone acetate. AB - A chlorocoulometric method for the determination of small amounts of hydrocortisone and hydrocortisone acetate is presented. The method is simple and rapid, the results obtained are accurate and reproducible. It can be successfully applied to the determination of hydrocortisone and hydrocortisone acetate in pharmaceutical formulations. PMID- 1930556 TI - Gas-liquid chromatographic analysis of cellular fatty acid methyl esters in Aeromonas species. AB - The cellular fatty acids of 39 strains belonging to the genus Aeromonas (Aeromonas hydrophila, Aeromonas caviae, Aeromonas sobria, Aeromonas media, Aeromonas schubertii, Aeromonas veronii) were determined by high resolution gas liquid chromatography. The fatty acid profiles were characterized by major amounts (60% or more) of one saturated (hexadecanoic acid = 16:0) and two unsaturated (hexadecenoic acid = 16:1 and octadecenoic acid = 18:1) acids. While the majority of the strains of the six species exhibited, qualitatively, very similar fatty acid compositions, only minor and inconsistent differences could be observed which would be useful for a distinction of the different taxons. The following fatty acids were qualitatively identified: 12:0, i-13:0, 14:0, 3-OH 13:0, i-15:0, 15:0, 2-OH 14:0, 3-OH 14:0, i-16:0, 16:1, 16:0, i-17:1, i-17:0, a 17:0, 17:0 cyclopropane, 17:1, 17:0, 18:1 (3 isomers), 18:0 and i-20:0. Excellent congruence was found in reproducibility studies. Fatty acid analyses show a great homogeneity within the group and the technique does not appear to be the ideal method in distinguishing between Aeromonas species. PMID- 1930557 TI - Evaluation of protective mAbs against Pseudomonas aeruginosa outer membrane protein I by C1q binding assay. AB - Seven monoclonal antibodies (mAbs) against the outer membrane proteins (OPRs) F, H and I of Pseudomonas aeruginosa were prepared. Western blot analysis has shown the mAbs to cross-react with all 17 serotypes of P. aeruginosa according to the International Antigenic Typing Scheme. Two of the mAbs (2A1, 6A4) protected mice against fatal P. aeruginosa pneumonia. The protective potential of the mAbs did not correlate with the immunoglobulin isotype nor with the fine antigen specificity and the in vitro bactericidal activity of the mAbs. Only the binding of the first complement component C1q of the mAbs as estimated in vitro by an ELISA was significantly correlated with their protective potential. PMID- 1930558 TI - L-prolineaminopeptidase activity as a tool for identification and differentiation of Serratia marcescens, Serratia liquefaciens and Hafnia alvei strains. AB - S. marcescens (316 strains), S. liquefaciens (10 strains) and Hafnia alvei (20 strains), in contrast to 18 other Enterobacteriaceae species, hydrolyzed L proline-4-nitroanilide within 30 min at 37 degrees C. In this way, rapid identification of these species is possible. The substrate is applied in solution or in a paper disc. The substrate optimum of Hafnia alvei strains proved to be 16 times lower than that of the Serratia spp. Application of a tenth of the substrate concentration necessary for identification of Serratia spp. allows a rapid differentiation between the two species. PMID- 1930559 TI - Listeriolysin negative mutants of Listeria monocytogenes specifically stimulate T lymphocytes mediating protection and granulomatous inflammation. AB - The ability of several listeriolysin O negative mutants of the virulent EGD strain of Listeria monocytogenes to activate specific T cell responses in vitro and in vivo was determined. A T cell line and a derived clone specific for Listeria monocytogenes, strain EGD, which are able to adoptively transfer protection and granuloma formation were examined. Specificity testing showed no difference between listeriolysin positive and negative strains to induce proliferation of the T cell lines and clones. Similar results were obtained when we examined T cell mediated granuloma formation in the livers of mice previously immunized with viable bacteria. Granulomatous inflammation could be elicited by i.v. application of heat killed bacteria of listeriolysin positive as well as of negative bacteria. Thus, the expression of the heat induced 60KD listeriolysin protein is not a prerequisite for the stimulation of Listeria-specific T lymphocytes mediating protection and granuloma formation. PMID- 1930560 TI - Detection of antibody formation in mice, rats and rabbits immunized with different Pneumocystis carinii antigens. AB - Antibody formation to P. carinii of human origin was determined by an indirect immunofluorescence antibody assay (IFA) after immunization of mice, rats and rabbits with pronase-treated whole cysts and soluble antigen in order to obtain more detailed data about the production of polyclonal antibodies. Antibody titre profiles over defined periods have shown that noticeable differences between the immunoreactions to whole cysts and soluble antigen occur. The soluble antigen produced an earlier and stronger titre rise (peak titres of up to 1:2560 2 to 4 weeks after immunization). In contrast to this, whole cysts produced equally high, although retarded, antibody titre peaks only in normal mice and rats and when the dose had been doubled. Nu/nu mice failed to demonstrate any reaction to these P. carinii immunogens. Cross-reactivity of the antibodies with P. carinii antigen from rat lungs was demonstrated. Possible reasons for different immunoreactions to these antigens, the importance of proteolytic digestion for the results obtained and the potential applicability of these polyclonal antibodies to a histochemical demonstration of the parasite are discussed. PMID- 1930561 TI - A comparison of the occurrence of borreliae in nymphal and adult Ixodes ricinus ticks. AB - The prevalence of borreliae in 209 nymphal and 251 adult Ixodes ricinus was investigated in two areas of southern Moravia, Czechoslovakia, using the dark field and the Giemsa stained-smear techniques. The proportions of infected ticks were 3.8% in nymphs and 10.6% in adults of area A, while they were 29.1% in nymphs and 35.9% in adults of area B. The mean number of borreliae per tick was about 3 to 10 times greater in adult than in nymphal I. ricinus. The results indicate a significant role of nymphal I. ricinus in the ecology of Borrelia burgdorferi and in the epidemiology and epizootiology of Lyme borreliosis. PMID- 1930562 TI - Crossed immunoelectrophoresis applied to representative strains from 11 different Pasteurella species under taxonomic aspects. AB - Crossed immunoelectrophoresis evaluated on a numerical basis revealed a close antigenic relationship between species of the genus Pasteurella. By cluster analysis, 4 groups on similarity levels between 87% and 72% S could be separated which were connected by a minimum level of 69.5% S. One subgroup included all biovars or subspecies consisting of strains with mucoid growth. Another feature governing the antigenic relationship seemed to be the host range of Pasteurella species. Despite a considerable number of cross-reacting antigens, representative strains of the genera Haemophilus and Actinobacillus were clearly separated from Pasteurella. Similarly, "Pasteurella" haemolytica and Taxon 16 strains tested did not belong to this genus. An Escherichia coli strain showed a higher number of cross-reacting antigens, confirming known antigenic relationship among Gram negative bacterial species. PMID- 1930563 TI - Multilocus enzyme analysis of the genus Aeromonas and its use for species identification. AB - A total of 153 Aeromonas strains were analyzed by multilocus enzyme electrophoresis. All 11 genetic loci were polymorphic with three to 14 alleles per locus (average 6.55). The genetic diversity of each locus varied between 0.095 for indophenol oxidase and 0.881 for the fast variety of malic enzyme. Cluster analysis of the 122 enzyme types revealed a good correlation with taxonomic groupings as determined by DNA-DNA hybridization. In conjunction with biochemical analysis, as few as two enzymes may be sufficient for the identification of all species in the genus Aeromonas. PMID- 1930564 TI - Effect of calcium ions on cell surface electrostatics of Bacteroides gingivalis and other oral bacteria. AB - Surface electrostatics of Bacteroides gingivalis and other oral bacteria were examined. A polarization circuit was employed using platinum electrodes exposed in each bacterial suspension and the number of bacteria adsorbed to the anode and cathode were then estimated. In all bacteria (B. gingivalis, Streptococcus sobrinus, S. mutans, S. salivarius, S. sanguis and Actinomyces viscosus), the number of cells adsorbed to the anode were much greater than the number of cells adsorbed to the cathode. Treating these bacteria with calcium ions tended to decrease the ratio of the number of cells adsorbed to the anode to the number of cells adsorbed to the cathode in all bacteria examined. Moreover, in the case of B. gingivalis, the number of cells adsorbed to the anode and cathode was in an inverse relationship to the number counted before calcium ion treatment. These findings indicate that the cell surfaces of oral bacteria are generally negatively charged but only the cell surface electrostatics of B. gingivalis was dramatically affected by calcium ion treatment. Thus, divalent metal bridges such as calcium bridges contribute to the adherence of the periodontopathic bacterium, B. gingivalis rather than to that of other oral bacteria including cariogenic bacteria. PMID- 1930565 TI - Isolation and characterization of temperature sensitive mutants of the F5 deletion mutant of mycobacteriophage D29. AB - Seven thermosensitive mutants of the F5 deletion mutant of the mycobacteriophage D29 were described. The mutants were obtained using N-methyl-N'-nitro-N nitrosoguanidine (MNNG) mutagenesis, and were characterized using temperature shift assays, complementation and recombination tests, electron microscopy of infected host bacteria at non-permissive temperature, and serum blocking power. Mutants deficient in tail assembly, and mutants deficient in head and tail assembly were described. Mutants deficient in head assembly but capable of assembling tails were not isolated during this study. From the data, 3 provisional linkage map of the phage F5 was proposed. PMID- 1930566 TI - Urease production by Helicobacter (Campylobacter) pylori. AB - Urease activity of 50 Helicobacter pylori (H. pylori) strains was assessed employing a photometric assay. Urea hydrolysis reached a maximum in the late log phase and during the plateau phase of bacterial growth. The reaction time of H. pylori urease was significantly shorter than that of other urease producing bacteria (P. mirabilis, P. vulgaris, K. pneumoniae, K. oxytoca). Increasing the reaction temperature hardly led to an acceleration of the quick urea hydrolysis of H. pylori, in contrast to the situation with P. mirabilis. Acetohydroxamic acid showed a dose-dependent non-competitive suppression of urease production, whereas 9 antibiotics in subinhibitory concentrations did not influence urease production of H. pylori. PMID- 1930567 TI - Isolation of Klebsiella terrigena from human feces: biochemical reactions, capsule types, and antibiotic sensitivity. AB - Colonization of the human intestinal tract by a newly proposed species, K. terrigena, was investigated. 5377 different stool specimens from healthy persons (food handlers) yielded 50 isolates (0.9%). Biochemically, low frequencies in the degradation of urea, dulcitol, and utilization of citrate at 37 degrees C were found when compared to K. pneumoniae. At 30 degrees C, urea hydrolysis was observed twice as often as at 37 degrees C. Apart from ampicillin, K. terrigena was susceptible to 12 other antimicrobial drugs tested. Multiple drug resistance was rare, few isolates being resistant against 2-4 antibiotic agents. Capsule typing revealed 30 different serotypes, K 70 and K 14 were the most frequent. Six strains expressed capsule types K 2 and K 5, which have been reported to be associated with virulence in K. pneumoniae. A possible pathogenic role of K. terrigena is discussed. PMID- 1930568 TI - Comparison of three selective isolation media for the detection of L. monocytogenes in foods. AB - 391 different foods were examined in order to compare three selective isolation media for Listeria: blood agar with nalidixic acid, Palcam agar, Listeria selective Oxford medium (Oxford agar). The percentage of positive samples (presence of Listeria in 25 g) obtained on the three media after an enrichment procedure is identical: 15.8%. The species L. monocytogenes is found in respectively 8.43%, 8.43% and 8.18% of the foods examined on Palcam agar, Oxford agar and nalidixic acid agar; this represents more than 50% of the isolates of the genus Listeria. However, Palcam agar and Oxford agar offer the advantages of a great reduction of the development of the contaminating microflora and a clearly less fastidious reading. The technique used for the direct counting of L. monocytogenes on these two selective media does not allow the detection of a low contamination of foods (theoretical positivity threshold = 100 Listeria/g): 65.2% of the positive samples would not have been detected without prior enrichment. 41.1% of the isolated L. monocytogenes belong to serovar 1/2a, 5.8% to serovar 1/2b, 20.58% to serovar 1/2c, 5.8% to serovar 3b and 24.47% to serovar 4b. PMID- 1930569 TI - Susceptibilities of motile Aeromonas sp. to antimicrobial agents. AB - Resistance to antimicrobial agents of 106 isolates of motile Aeromonas sp. was characterized. The results indicated that in vitro susceptibilities among the three species of the motile Aeromonas sp. were similar, and only the distribution of susceptibility to cephalothin was different. The percentage of resistance of A. sobria strains was lower than the percentage of the resistant strains of A. hydrophila and A. caviae. All of the isolates were susceptible to kanamycin, nalidixic acid, tobramycin, amikacin, netilmicin, cefuroxime, ceftriaxone, cefoperazone and cefotaxime. Three of the tested strains (two A. hydrophila and one A. caviae) transferred resistance plasmids to the Aeromonas hydrophila recipient. PMID- 1930570 TI - Antibody response to pneumococcal vaccination in the elderly. AB - In order to evaluate the antibody response to primary pneumococcal vaccination in the elderly, 20 healthy persons aged 60 years or older, (mean age 62.8) were vaccinated with a 23-valent pneumococcal polysaccharide vaccine (Pneumovax 23). Blood samples were taken before and 4 weeks after vaccination and pneumococcal antibody concentrations were measured by ELISA and compared with those obtained after vaccination of younger persons (mean age 39 years). Significantly lower anti-type 2 antibody concentrations were found in the elderly after vaccination. Apart from this, no other significant differences were found neither in pre- and post-vaccination antibody concentrations nor in antibody fold increases between the two groups. PMID- 1930571 TI - Some unusual members of the family Pasteurellaceae isolated from human sources- phenotypic features and genomic relationships. AB - Twelve human isolates exhibiting the properties of the family Pasteurellaceae but phenotypically deviating from established species, or resembling species of animal origin that are only rarely reported to occur in human materials, were checked for their identities by DNA-DNA hybridization. The collection consisted of one strain of Actinobacillus lignieresii, two strains of Actinobacillus hominis (mannose-positive), two hitherto undescribed Actinobacillus or Actinobacillus-like species, [Pasteurella] haemolytica biovar T, CDC group HB-5 (initially oxidase and indole-negative), a new species in the [Haemophilus] aphrophilus [Haemophilus] segnis group, a new sucrose-negative and gas-producing Pasteurella-like species, and three strains of Bisgaard's Pasteurella-like taxon 16. Some diagnostically useful features of these unusual human Pasteurellaceae are described. PMID- 1930573 TI - A comparative investigation and identification of Leptospira interrogans serogroup icterohaemorrhagiae strains by monoclonal antibody and DNA fingerprint analyses. AB - The identification of Leptospira interrogans icterohaemorrhagiae strains from a number of Reference Laboratories were confirmed using monoclonal antibody (MoAb) and DNA restriction endonuclease (EcoR1) analyses. With a few exceptions, strain fidelity was demonstrated. Three clinical isolates and one isolate from a rat (Rattus norvegicus) were identified on DNA fragment patterns and found to be similar to the reference strains, icterohaemorrhagiae copenhageni, I. "icterohaemorrhagiae" Ictero I and I. icterohaemorrhagiae RGA. PMID- 1930572 TI - Polyphasic taxonomic study of the genera Gordona and Tsukamurella including the description of Tsukamurella wratislaviensis sp. nov. AB - Representatives of the genera Gordona and Tsukamurella together with related actinomycetes were the subject of chemotaxonomic, numerical taxonomic and DNA homology studies. In the numerical analysis the organisms were examined for 116 unit characters and the data sorted using the simple matching, Jaccard and pattern coefficients; clustering was achieved using the unweighted pair group method with arithmetic averages algorithm. The numerical groupings were not affected by the statistics used or by test error, estimated at 1.9%. The numerical taxonomic data supported the integrity of the four validly described species of Gordona but indicated that the genus Tsukamurella might encompass a species in addition to Tsukamurella paurometabola. The putative new strains had chemical, enzymic, nutritional and tolerance properties consistent with their assignment to the genus Tsukamurella and formed a DNA homology group corresponding to the one formed by the Tsukamurella paurometabola strains. It is proposed that the new taxon be assigned to the genus Tsukamurella as Tsukamurella wratislaviensis. PMID- 1930574 TI - Modulation of antimicrobial effects of beta-lactams by amino acids in vitro. AB - Glycine as well as 11 and 10, respectively, out of a total of 12 D-amino-acids tested increased the antimicrobial efficacy of imipenem (IMI) and of ampicillin (AMP) using the serosensitive strain E. coli ATCC 8739. D-proline was ineffective in assays with IMI as well as D-proline and D-leucine in assays with AMP. - In contrast, L-amino-acids behaved differently: In assays with IMI, 9 out of 13 isomers were ineffective whereas 3 were antagonistic (L-phenylalanine, L-serine, L-tryptophan). In combination with AMP, however, 10 L-amino acids had an antagonistic effect and 2 (L-leucine, L-methionine) were ineffective. L-alanine was an exception and showed a synergism with both antibiotics which was assumed to have been due to a racemase activity of cells. - Seroresistance of E. coli apparently reduced the synergistic effect of glycine and beta-lactams. - Glycine, alanine and tryptophan lost their typical synergistic or antagonistic effect with AMP when tested as di- or tri-amino-acid compounds. This was not the case with di L-alanine - It is supposed that the synergistic effect of glycine or of D-amino acids with beta-lactams can be explained mainly by an inhibition of carboxypeptidases. PMID- 1930575 TI - Influence of cefpodoxime on selected immunological functions and bacterial pathogenicity factors in vitro. AB - The influence of a new oral cephalosporin cefpodoxime, on several interactions of the host-parasite relationship was investigated. Pretreatment of polymorphonuclear granulocytes (PNG) with cefpodoxime at therapeutical dosage in vitro did not have a significant effect on chemotaxis and luminol-dependent chemiluminescence. On the other hand, human serum did not exert a considerable effect on the bactericidal activity of cefpodoxime on Klebsiella pneumoniae and Staph. aureus. Serum resistance of Klebsiella pneumoniae was not altered after pretreatment with cefpodoxime 1/16 MIC (0.03 micrograms/ml) for 3 to 27 hours. PMID- 1930576 TI - Effects of active and passive immunization in the Mycoplasma arthritidis infection of rats. AB - Viable, heat-inactivated, formalin-inactivated and sonicated Mycoplasma (M.) arthritidis antigens as well as immune sera against M. arthritidis and spleen cells from Lewis rats recovered from M. arthritidis infection were injected into naive Lewis rats prior to a challenge infection with 10(7) cfu of M. arthritidis and tested for their protective effects. Viable mycoplasmas induced arthritis combined with the production of high titers of antibodies against M. arthritidis and resistance to a second infection. The application of the inactivated M. arthritidis-antigens in emulsion of incomplete Freund's Adjuvant (ICFA) to naive rats, which also induced a strong antibody production, as well as the inoculation of reconvalescent serum from rats infected with M. arthritidis and hyperimmune serum against M. arthritidis from rabbits and mice protected rats also from an outbreak of arthritis after challenge. The injection of sonicated M. arthritidis antigen without ICFA which failed to induce the production of antibodies and the transfer of spleen cells from rats recovered from M. arthritidis infection had no protective function. The investigations showed, that antibodies play an important role in the prevention of M. arthritidis infections in Lewis rats. PMID- 1930577 TI - A phagocytosis capacity assay: parallel measurement of the phagocytosis and the intracellular killing in granulocytes and the influence of some substances on these processes. AB - A radiometric technique is described for the assessment of phagocytosis and killing of viable yeast cells by granulocytes. This technique does not require separation of extra- and intracellular microorganisms. In this method the phagocytes which contain viable yeast cells (Saccharomyces cerevisiae and Candida albicans) were disrupted by Triton X-100, and only the remaining yeast cells were isotope-labelled. The uptake of [75 Se]L-selenomethionine was used to measure the killing ability of phagocytes. This method is recommended to measure the influence of biological and pharmacological agents to ingest and kill leucocytes in vitro. The following substances affected phagocytosis and killing: Granatomycin C (decreased phagocytosis), cis-DDP (no influence), bestatin (stimulation of phagocytosis) and Z 190/69-HCl (oxazole) (stimulation of phagocytosis and killing). PMID- 1930579 TI - Isoenzymes in Entamoeba as detected by isoelectrofocusing. AB - Two major zymodemes from different Entamoeba histolytica strains were detected, despite different growth conditions, using isoelectrofocusing in ultrathin gels. One was associated with strains cultured from symptomatic patients, while the other was associated with microorganisms obtained from clinically symptomatic persons. PMID- 1930578 TI - Toxin production by atypical strains of Vibrio cholerae E1 Tor under different cultural conditions. AB - It was observed that at 37 degrees C under in vitro conditions, aerobic culture filtrates of a few strains of Vibrio cholerae biotype El Tor isolated from diarrhoeal cases produced a minute amount of toxin which failed to elicit a positive ileal loop reaction like toxigenic strains. Thus, these strains showed an atypical behaviour in their toxin producing ability. At 25 degrees C and 30 degrees C under aerobic cultural conditions enhanced toxin production was noticed in toxigenic strains, but these temperatures did not affect the toxigenicity of the atypical strains. The atypical Vibrio cholerae El Tor strains exhibited enhanced toxin production only at 37 degrees C under anaerobic conditions and the amount of toxin produced was akin to those of the toxigenic strains. In comparison to aerobic conditions, growth was observed to be comparatively lower under anaerobiosis both in the toxigenic and atpyical V. cholerae strains. Moreover, in contrast to the toxigenic strains, the toxin did not remain membrane bound in these atypical strains at 37 degrees C and aerobic cultural conditions. PMID- 1930580 TI - Intestinal worm burden and serum cholesterol or lipid concentration in a Shipibo population (Peru). AB - Paired samples of stool and serum of 32 members of the Shipibo tribe resident in the rain forest of the Peruvian lowlands were tested for worm egg count and serum lipid parameters, respectively. 90% of the stool samples tested were found to contain eggs or larvae of several worm species, most commonly 3 or 4 different species. Serum lipid levels were found to be relatively low, most probably due to a low proportion of dietary fat ranging from 16-31%. Statistical analysis showed a significant inverse correlation between worm egg excretion and HDL levels which was true for hookworm, strongyloides and trichuris, but not for ascaris. The mechanisms underlying the observed association between intestinal worm load and HDL reduction are not completely understood and may include reduced HDL synthesis in the gut wall due to inflammatory and/or toxic irritation. PMID- 1930581 TI - Democrats unveil health plan. PMID- 1930582 TI - The effectiveness of Dermagran topical therapy for treating chronic wounds in nursing facility residents. PMID- 1930583 TI - The American Association of Homes for the Aging. PMID- 1930584 TI - Fatal attraction: Foley catheters. PMID- 1930585 TI - Achieving a state of urinary continence for residents of nursing facilities. Part II: Urodynamics and laboratory investigation. PMID- 1930586 TI - A new tool for evaluating patient support surfaces. Part I: A guideline for making practice decisions. PMID- 1930587 TI - The management of selected complications following ileo-anal anastomosis with pouch reservoir. Part II: Complications following ileostomy closure. PMID- 1930588 TI - Utilizing a prevention and treatment protocol for skin breakdown secondary to urinary incontinence. PMID- 1930589 TI - Writing for journal publication. PMID- 1930590 TI - 15 ways to improve test performance. PMID- 1930591 TI - Red cell distribution width and mean corpuscular volume: clinical applications. PMID- 1930592 TI - The "how to's" of touch. AB - Touch, described as the most important of all the senses (Clement, 1987), confirms the reality perceived through the other senses and is a central part of the communication process (Montague, 1971; Mintz, 1969). Touch can be a tremendously supportive nursing technique. A pat on the shoulder, a hug, or a squeeze of the hand can create warmth and closeness that facilitates communication, decreases anxiety, and enables patients to tolerate discomfort. However, touch needs to be used deliberatively, with empathy, and with close attention to each person's unique needs. It is a nursing intervention that needs to be tailored to the patient's needs and responses. PMID- 1930593 TI - ABCD's of assessing skin lesions. AB - The ABCD's are easy-to-remember guidelines to help differentiate between normal and suspicious skin lesions. Tips for assessing the skin and a discussion of the characteristics of nonmelanoma and melanoma lesions are included. Measures to help prevent skin cancer are also discussed. PMID- 1930594 TI - Mobility and ambulation. Not easy tasks for all older adults. AB - Interventions to preserve muscle strength and return the older adult patient to self-care activities are extremely important. However, due to the severe illness of the older adult, interventions to prevent loss of muscle strength may be overlooked in the acute care hospital. This article identifies reasons for rapid loss of muscle strength in older adults and reviews basic interventions needed to prevent this complication of immobility. PMID- 1930595 TI - Dorothy Nicholas--the nurse--the writer--the woman. PMID- 1930596 TI - Reminiscence therapy as a nursing intervention. PMID- 1930597 TI - Nursing's approach to the care of the elderly. AB - This article describes the role and challenges nursing has assumed in the care of elderly patients in an Adult Day Health Care Program (ADHC). It describes the application of the standards of nursing practice from gerontological and rehabilitative nursing settings along with the standards (for Adult Day Care) proposed by the National Institute on Adult Day Care in an interdisciplinary, community based practice setting. PMID- 1930598 TI - History of American military nursing. PMID- 1930599 TI - Caring for hospitalized infants. AB - Infancy is a time of rapid physical growth and maturation of body systems. Infants have limitations in physiological functioning and are very dependent on adult knowledge and care. Therefore, when infants are hospitalized, nursing interventions must be adapted to safely and adequately meet their unique needs. This article explains the nature of infant growth and development and emphasizes those aspects that require special nursing considerations. PMID- 1930600 TI - Life and lessons. PMID- 1930601 TI - Optimal training of nurses (from a USSR experiment of the Rostovskii District Medical School). PMID- 1930602 TI - You are reading Advancing Clinical Care's (ADCC) final issue. PMID- 1930603 TI - How-to's for greater cultural sensitivity. PMID- 1930604 TI - Chemical abuse in nurses. We must no longer enable, ignore, deny, or excuse this growing public and professional epidemic. AB - Chemical abuse is a symptom of a deep and complex physical, psychosocial, and spiritual problem which, in the nurse, can have particularly disastrous results. Clearly there is no "quick fix," nor one solution. Education is a crucial element in the prevention, early identification, and timely treatment of chemical abuse. When awareness is increased, nurses will be better prepared to recognize, prevent, and confront the growing problem of chemical abuse in the profession and in society at large. PMID- 1930605 TI - Assessing color changes for dark skinned patients. PMID- 1930606 TI - Recent advances in obsessive-compulsive disorder. AB - A growing body of evidence from clinical phenomenology, including associated disorders, brain imaging, and neuropharmacologic studies, links the classic psychiatric syndrome of obsessive-compulsive disorder (OCD) to basal ganglia dysfunction and to the serotonin system. At present, OCD is the psychiatric syndrome for which a specific neurologic dysfunction is most strongly suggested, and for which a particularly compelling animal model has been found. It is proposed that dysfunction of basal ganglia-thalamic frontal cortical loops produce "positive" symptoms of excessive grooming, checking, and doubt most common in OCD. Perhaps most intriguing are preliminary data from clinical trials that a spectrum of other abnormal behaviors resembling excessive grooming in both animals and humans may be related to OCD. An ethologic perspective is suggested. PMID- 1930607 TI - Has OCD research gone to the dogs? Comments on "Recent advances in obsessive compulsive disorder". PMID- 1930608 TI - Advances in obsessive-compulsive disorder. PMID- 1930609 TI - Effects of diazepam on cerebral metabolism and mood in normal volunteers. AB - The effects of diazepam on regional cerebral metabolism were examined in eight healthy volunteers using positron emission tomography with 18-fluorodeoxyglucose as the tracer. Each subject was tested three times, at 1-week intervals, with placebo, a low oral dose of diazepam (0.07 mg/kg), and a moderate dose of diazepam (0.14 mg/kg). Subjects completed mood questionnaires before and at regular intervals after taking the drug, and performed a vigilance task during the 60-minute period of tracer uptake. The effects of the drug on cerebral metabolism were examined alone and in relation to the subjective and behavioral effects of the drug. Both doses of diazepam decreased global (whole brain) metabolic rate but did not affect specific regions differentially. Subjects experienced sedative like effects during all three scans (placebo as well as drug). Compared to placebo, both doses of diazepam decreased anxiety, and neither dose produced significant impairment of task performance. Neither the subjective nor behavioral drug effects were correlated with the changes in metabolic rate. Thus, diazepam decreased whole brain metabolic rate at doses that produced only modest subjective or behavioral effects. The changes in metabolic rate were not clearly related to other observable drug effects. PMID- 1930610 TI - Affinities of fluoxetine, its enantiomers, and other inhibitors of serotonin uptake for subtypes of serotonin receptors. AB - The new antidepressant drugs, fluoxetine (and its enantiomers), citalopram, indalpine, paroxetine, and femoxetine show relatively weak affinities for 5-HT receptors as measured by radioligand binding to 5-HT-1(A,B,C and D), 5-HT-2, and 5-HT-3 subtypes. Fluoxetine and R(-)-fluoxetine, at near micromolar concentrations, inhibit 3H-mesulergine binding to 5-HT-1C receptors in bovine choroid plexus, and the R(-) enantiomer is 23 times more potent than the S(+) enantiomer. However, the near nanomolar potencies of these drugs as inhibitors of 5-HT uptake most likely account for their pharmacologic effects in animals. PMID- 1930611 TI - The effects of thyroid hormones on potassium-stimulated release of 3H-GABA by synaptosomes of rat cerebral cortex. AB - Depolarization-induced release of neurotransmitters from nerve endings is triggered by the rapid entry of Ca through voltage-sensitive channels. Low (1 to 10 nmol/L) concentrations of L-triiodothyronine (T3), but not D-T3, reverse T3 (rT3) or L-thyroxine (T4), enhance fast-phase depolarization-induced 45Ca uptake by rat brain synaptosomes. In the present study the effects of thyroid hormones on the release of 3H-gamma-aminobutyric acid (3H-GABA) by cerebral cortical synaptosomes from adult male Sprague-Dawley rats were determined by a superfusion technique. It was found that low (1 to 10 nmol/L) concentrations of T3, but not D T3, rT3, or T4, significantly enhanced Ca-dependent 3H-GABA release by synaptosomes exposed to a high K depolarization buffer for 5 sec. Low concentrations of T3 did not enhance basal 3H-GABA release or release produced by exposure to depolarization buffer for 30 seconds. Much higher concentrations (10 mumol/L) of both T3 and T4, but not rT3, D-T3, or D-T4, stimulated 3H-GABA release produced by exposure to depolarization buffer for 30 seconds. PMID- 1930612 TI - Nicardipine protects against chronic ethanol- or haloperidol-induced supersensitivity to apomorphine-induced aggression. AB - Affective apomorphine-induced aggression was induced in originally nonaggressive rats after withdrawal from prolonged ethanol or haloperidol treatment. If the animals were co-administered Ca(2+)-channel blockers like diltiazem or verapamil the aggressive response to apomorphine was markedly decreased. Nicardipine (2 and 5 mg/kg b.i.d.) significantly attenuated the aggression-enhancing effect of chronic ethanol or haloperidol withdrawal in nonaggressive rats. Chronic nicardipine, alone, did not enhance aggressive behavior in the nonaggressive rats. Acutely, it suppressed apomorphine-induced aggression but did not alter open field activity when injected into aggressive rats. These results demonstrate that a Ca(2+)-channel blocker of the dihydropyridine type can prevent the development of an ethanol or haloperidol-withdrawal supersensitivity to apomorphine-induced aggression. It attenuates the aggression-inducing effect of apomorphine without impairing general activity. PMID- 1930613 TI - Diazepam and haloperidol. Effect on regional brain homovanillic acid levels. AB - Diazepam lowered homovanillic acid levels in brain regions from untreated and haloperidol-treated rats. However, there was evidence of a biphasic effect in that 2 mg/kg was more effective than 10 mg/kg under several conditions. Diazepam was more effective in restoring regional HVA toward control levels following doses of haloperidol in the low clinical range (0.1 to 0.2 mg/kg) than following higher doses. With respect to maximizing dopamine receptor blockade and minimizing compensatory presynaptic activity in the acute treatment of psychotic conditions, our data provide some support for the use of modest doses of neuroleptics and benzodiazepines. PMID- 1930614 TI - Circadian locomotor activity rhythms in Alzheimer's disease. AB - Circadian motor activity rhythms in 19 severely demented, institutionalized patients with Alzheimer's disease (AD) were evaluated with small, waist-worn electronic monitors which recorded 5-minute epochs for 48 to 72 hours. Controls were eight normal subjects of the same age (71 to 73 years) in a similar environment. As expected, computer-assisted analysis indicated more than twofold average increases in nocturnal activity and in the proportion of nocturnal to total daily activity in the AD patients. In patients (n = 8) with virtually constant pacing, daytime activity was markedly increased over that of normal controls; these "pacers" also had a significantly decreased amplitude of the circadian activity rhythm compared with controls. Moreover, AD patients showed a marked phase-delay, with individual afternoon maxima (acrophases) averaging 2.1 hours later than in controls (p less than 0.005). These findings quantitatively document clinical observations that AD patients, and especially a subgroup with pacing behavior, have markedly disturbed levels and modulation of daily locomotor activity. They accord with reports of altered circadian rhythms of endocrine and other physiologic parameters in such patients. Activity monitoring may represent a relatively simple, objective measure with which to characterize demented patients and to assess responses to treatment. PMID- 1930615 TI - CSF and endocrine studies of premenstrual syndrome. AB - Eight women with prospectively documented premenstrual syndrome (PMS) underwent multiple samplings for estradiol, progesterone, prolactin, cortisol, and plasma 3 methoxy-4-hydroxyphenylglycol (MHPG) during an asymptomatic midcycle (late follicular) and a symptomatic premenstrual (late luteal) phase of the menstrual cycle. Cerebrospinal fluid (CSF) was collected for analysis of MHPG, norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), gamma-aminobutyric acid (GABA), homovanillic acid (HVA), tyrosine, tryptophan, beta-endorphin, prostaglandins, adrenocorticotropic hormone (ACTH), and arginine vasopressin (AVP). In subsequent months, a dexamethasone suppression test (DST) and a thyrotropin-releasing hormone (TRH) stimulation test were performed during midcycle and premenstrual phases. Significant results included increased CSF concentrations of MHPG in the premenstrual, as compared with the midcycle, phase of the cycle, and increased plasma cortisol concentrations during the midcycle phase. The DST showed a 62% overall rate of nonsuppression, irrespective of menstrual cycle phase. Though there were no abnormalities of thyrotropin-stimulating hormone (TSH) after TRH stimulation, the mean delta maximum prolactin values after TRH stimulation were higher than reported normal values both at midcycle and premenstrually. These pilot data suggest hormonal axes that might be worthy of further systematic investigation in future studies of PMS. PMID- 1930616 TI - Invited ACNP Lecture. The early history of modern psychopharmacology. PMID- 1930617 TI - Sleep in late-life recurrent depression. Changes during early continuation therapy with nortriptyline. AB - The sleep of thirty elderly patients with recurrent unipolar depression was examined at baseline (before acute treatment of the index episode) and again in a state of symptomatic remission with nortriptyline (mean steady-state level: 82.1 ng/ml). Continuation therapy with nortriptyline was associated with improvement of polysomnographic sleep maintenance (mainly in the third and fourth sleep cycles, to a level similar to that of controls), prolongation of rapid-eye movement (REM) sleep latency (exceeding that of controls), and potentiation of slow-wave activity during the first non-REM (NREM) sleep period. Clinical improvement, as measured by the Hamilton Depression Rating Scale, was significantly associated with shift of delta activity toward sleep onset (p less than 0.002), prolongation of REM sleep latency (p less than 0.0001), and improvement in sleep maintenance (p less than 0.0002). Multiple regression analysis showed that the single best correlate of clinical change was prolongation of REM sleep latency (i.e., prolongation of first NREM period). Perceived sleep quality improved significantly during early continuation therapy with nortriptyline, but not to the level reported by a group of 30 age- and sex matched healthy controls. The findings are consistent with the concept that anti depressant drug efficacy may depend upon strengthening of the homeostatic regulation of sleep and upon changes in the REM-sleep regulation. PMID- 1930618 TI - Biperiden administration in normal sleep and after rapid eye movement sleep deprivation in healthy volunteers. AB - Twenty-six healthy volunteers were randomly assigned to one of four groups. Groups Bip-4 and Bip-6, each with six subjects, received 4 and 6 mg of biperiden, respectively, and were studied on acclimatization, baseline, biperiden, and follow-up nights. Group REM-P (n = 7) and Group REM-Bip (n = 7) were studied on acclimatization, baseline, six nights of REM sleep deprivation, and one recovery (treatment) night with either placebo (group REM-P) or biperiden (group REM-Bip), and one follow-up night. Biperiden 4 and 6 mg increased REM sleep latency and biperiden 6 mg reduced REM sleep time. On the recovery night following REM sleep deprivation Group REM-P and REM-Bip showed an increase in sleep continuity. REM sleep time in the REM-P group was increased during the recovery (treatment) night (REM sleep recovery), while the REM-Bip group did not show a significant REM sleep increase during recovery (treatment) night. It was not until the follow-up night that REM sleep increased in the REM-Bip group. PMID- 1930619 TI - Inhibition of cholesterol side-chain cleavage. Part 5. Synthesis of 22-(p chlorophenyl) cholesterol analogues. AB - Three 22-(p-chloroaryl) analogues of cholesterol (6a-c) were synthesized and evaluated as potential inhibitors of the adrenal cholesterol side-chain cleavage enzyme, in comparison with the known 20-aryl analogue, 20-(p-chlorophenyl)-5 prenen-3 beta,20-diol (2b). All were potent inhibitors. An oxygen at C-22 (analogues 6a and 6b) enhanced the strong binding to the enzyme. Two compounds (6b and 6c) are potential substrates of the enzyme. Possible pharmaceutical uses for these compounds and their derivatives are discussed. PMID- 1930620 TI - Molecular modification of anticholinergics as probes for muscarinic receptors. Part 4. Ileal selective muscarinic antagonists. AB - Systematic studies of the structure-activity relationships of atropine-like anticholinergic drugs have provided valuable information about the nature of the muscarinic receptor. In this study, the pharmacological activities of the (Z) and (E)-isomers of 2-phenylcyclohexyl diethylaminoethyl ether (1 and 2, respectively) in the isolated rat left atrium were investigated and compared with their activities in the isolated rat ileum preparation. Compound 1 was found to be one of the most ileal selective muscarinic antagonists reported to date. Other data concerning possible differences in the receptor-bound conformations of tropate- versus benzilate-derived muscarinic antagonists are also presented. PMID- 1930621 TI - Synthesis and anti-inflammatory activity of 5-(1,4-dihydropyridyl)-tetrazol-2 acetic acids, esters and amides. AB - Thirteen 5-[3-(1,4-dihydropyridyl)]-2H-tetrazol-2-acetic acids (18-30), seventeen esters (4-17, 32, 35, 41) and eight amides (31, 32-34, 36-40) were synthesized in order to investigate the effect of alpha-substituents (R1 = H, Me) and 1,4 dihydropyridyl substituents (R2 = aryl, alkyl; R3 = phenoxy, methoxy or amino) on anti-inflammatory activity. The effects of the R1, R2 or R3-substituents were variable but highly interdependent. The relative order of anti-inflammatory potency was generally acid greater than amide and ester. Methyl 2-methyl-2-(5-[3 (4-phenyl-1-carbamoyl-1,4-dihydropyridyl)]-2H- tetrazol-2-yl) acetate (35) was the most effective anti-inflammatory agent in the group, reducing inflammation 96% at 5 hr after a 50 mg/kg po dose, relative to ibuprofen's 52% inhibition at 5 hr after a 100 mg/kg po dose. PMID- 1930622 TI - Controlled release microspheres based on Eudragit L100 for the oral administration of erythromycin. AB - The use of Eudragit L100, a copolymer based on methacrylic acid and methacrylic acid methyl ester, in preparing erythromycin microspheres is described. The microspheres were simply prepared in liquid paraffin by solidifying an Eudragit L100 in ethanol solution. When gelatin was incorporated in the solidifying solution, the resultant microspheres were more spherical and had a smooth surface. The size of the microspheres could be controlled by varying the Eudragit L100 concentration in ethanol, and erythromycin was incorporated with 60-70% efficiency. The degradation of erythromycin by acid was markedly protected when the erythromycin microspheres were coated with the polymer. The in vitro release rate of erythromycin from the microspheres was also modified by the coating process. The feasibility of preparing formulations of erythromycin for oral administration, which release the drug at a controlled rate, and protect the drug from gastric acid, is thus demonstrated. PMID- 1930623 TI - The use of micronized cellulose disintegrants as insoluble swellable matrices for sustained-release tablets. AB - Five cellulose disintegrants--low-substituted hydroxypropylcellulose (L-HPC), microcrystalline cellulose (MCC), carboxymethylcellulose (CMC), cross-linked NaCMC (C.L.NaCMC), and CaCMC-were evaluated as directly compressed matrices for sustained-release (SR) tablets in vitro, using procainamide hydrochloride as a model drug. Coarser particles (14-19 microns) of the jet mill ground disintegrants, as well as intact disintegrants, provided rapidly disintegrating tablets with fast drug release but finer particles (2.5-3.5 microns) provided matrix-type SR tablets. The SR tablets based on non-ionic polymers (L-HPC and MCC) did not disintegrate at any pH; those based on anionic polymers (C.L.NaCMC and CaCMC) did not disintegrate at pH 1.2, but they disintegrated gradually from the exterior in water and in a pH 6.8 medium. We conclude that the particle size and concentration of the cellulose disintegrants are determinant factors in the formulation of SR matrices. PMID- 1930624 TI - Stimulatory effect of oestradiol-17 beta and tamoxifen on gross cystic disease fluid protein 15,000 production and mRNA levels in T47D human breast cancer cells. AB - Oestradiol-17 beta and tamoxifen regulate the synthesis of a gross cystic disease fluid protein (GCDFP-15) in T47D human breast cancer cells. Dose-response curves of GCDFP-15 mRNA contents and GCDFP-15 levels in culture media and cells versus hormone or antihormone concentration have been established. Production of GCDFP 15 was increased by oestradiol-17 beta, tamoxifen and 4-OH tamoxifen. The effect of tamoxifen and 4-OH tamoxifen was greater than the effect of oestradiol-17 beta. Moreover, oestradiol-17 beta and 4-OH tamoxifen acted synergystically in enhancing GCDFP-15 release. The strong oestrogenic effect of the antioestrogen tamoxifen in regulating GCDFP-15 may reflect an unusual interaction between the tamoxifen-oestrogen receptor complex and the DNA oestrogen-responsive elements. As oestrogen control of GCDFP-15 depends also on the cell line studied, investigation of GCDFP-15 could extend our knowledge of the possible mechanism of action of oestrogens or antioestrogens. PMID- 1930625 TI - Evidence that androgen-binding protein endocytosis in vitro is receptor mediated in principal cells of the rat epididymis. AB - We have studied the binding of [125I-iodo]androgen-binding protein (ABP) and of [3H]delta 6-testosterone photoaffinity-labelled ABP to receptors in the plasma membrane of rat epididymal cells in three ways: ABP binding to a Triton X-100 solubilized membrane extract, ABP binding to isolated epithelial cells in suspension and autoradiography of segments of dissected epididymides after in vitro intraluminal injection of labelled ABP. The binding of iodinated ABP to the receptor was similar to that of photoaffinity-labelled ABP in gel filtration. The ABP-receptor complex was eluted from Superose 6 gels as an aggregate, with a molecular mass of 2000 kDa. It was separated into two peaks by sucrose gradient ultracentrifugation, with respective sedimentation coefficients of 18.4 and 9.0 s. The activity of the receptor (ABP-binding capacity/mg protein) was tenfold higher in the caput than in the cauda. The binding of ABP to the receptor was pH dependent, being almost abolished at pH less than 4. The binding at 4 degrees C of photoaffinity-labelled ABP to epithelial cells corresponded to two types of binding sites. The numbers of high-affinity and low-affinity sites per cell were 1600 and 7700 respectively; the association constants of these sites were 67.9 and 2.8 litres/nM respectively. The binding was decreased by treatment of the cells with trypsin or incubation in the presence of EDTA. The binding in vitro of labelled ABP to the epididymis epithelium reached a maximum after about 20 min at 4 degrees C. In the autoradiographic study the tracer was found to be closely associated with coated pits, coated vesicles, endosomes and pale multivesicular bodies. Treatment of rats with cycloheximide significantly reduced the uptake of the tracer. Perfusion in vitro of epididymides with chloroquine produced a fourfold increase of the tracer in endosomes and multivesicular bodies. PMID- 1930626 TI - Identification of antisense transcripts of the chicken insulin-like growth factor II gene. AB - Insulin-like growth factor-II (IGF-II) is a polypeptide mitogen which is believed to play an important role in fetal development. The human and rat IGF-II genes are complex transcription units, which contain multiple promoters and polyadenylation sites and which exhibit alternate splicing of their primary transcripts. In order to study IGF-II gene expression during chick embryonic development, we screened a 10-day chick embryo cDNA library with a human IGF-II cDNA probe. We isolated a clone, designated cigf, that was comprised, in part, of sequences homologous to the second coding exon of the human, mouse and rat IGF-II genes. Comparison of the nucleotide sequence of cigf with that of the corresponding genomic clone indicated that cigf was derived from a spliced antisense transcript of the chicken IGF-II gene, which overlapped the second coding exon. Northern blotting experiments with single-stranded RNA probes synthesized using cigf DNA as a template showed that stage 22 and stage 36 chick embryos contained sense strand IGF-II transcripts of 1.4, 2.2, 4.7 and 7.0 kb and antisense strand transcripts of 0.7, 1.3, 1.8, 2.5, 4.9, 6.0 and 8.0 kb. The pattern of sense strand IGF-II transcripts was similar to that previously found in rat fetal tissues. Whilst there are precedents for the transcription of both strands of a single gene, this is the first evidence for antisense transcription of an IGF gene. The functions of the antisense transcripts remain to be determined. These findings demonstrate a further level of complexity in the IGF II transcription unit and indicate that studies of IGF-II transcript distribution performed with double-stranded probes should be interpreted with caution. They also suggest explanations for the recent finding that IGF-II peptides are present at much lower levels in embryos than expected from the high levels of IGF-II transcripts present. PMID- 1930627 TI - Isolation of the mouse cytochrome P450J (CYP2E1) cDNA and its reciprocal testosterone regulation in kidney and liver. AB - A hybridization probe that is homologous to the B2 short interspersed repetitive element detects an mRNA in mouse kidney and liver that is regulated by androgen. Administration of testosterone induces this mRNA in kidney and represses it in liver. The mRNA was cloned by first using the B2 probe to select 48 cDNA clones from an androgen-induced kidney library. These clones were then tested for their androgen response by hybridizing them with probes made by reverse transcription of basal and testosterone-treated kidney poly(A)+ RNA. Any homology to the B2 sequence was masked by prehybridizing the filters to an excess of non-radioactive RNA synthesized from a B2 sequence cloned into a riboprobe vector. A unique sequence was subcloned from the largest androgen-responsive cDNA clone. A radioactive riboprobe generated from the unique sequence subclone detected an androgen-responsive mRNA in Northern blots with the same electrophoretic mobility as the predominant androgen-responsive mRNA detected with the B2 homologous riboprobe. The riboprobe also detected a unique sequence in Southern blots of genomic DNA. This subclone was then used as the probe to isolate a full-length cDNA clone from a second androgen-induced kidney library. When sequenced, this full-length cDNA of an androgen-responsive, B2-containing mRNA showed strong homology to the rat and human cytochrome P450J and the rabbit cytochrome P450 3a genes (CYP2E1). It showed only weak homology to the mouse testosterone 15 alpha hydroxylase gene (CYP2A3) which is also regulated reciprocally by androgen in kidney and liver. The sequence of mouse P450J is identical to the B2 homologous mRNA previously named B2+ mRNAx which is abundant in mouse liver. PMID- 1930628 TI - Genetic variation of the glucocorticoid receptor from a steroid-resistant primate. AB - The neotropical cotton-top marmoset (Saguinus oedipus) is a New World primate known to have markedly increased total and free plasma cortisol concentrations when compared with Old World primates including man. The relative end-organ 'resistance' to glucocorticoids found in various New World primates has been attributed to a glucocorticoid receptor (GR) with diminished affinity for glucocorticoids. It has been demonstrated that the marmoset GR has approximately tenfold lower binding affinity for dexamethasone when compared with the human GR. We have examined the primary structure of the marmoset GR by molecular cloning and sequencing of GR functional domains. A library of cDNA clones was constructed in the phage vector gamma gt10 using poly(A)+ RNA from a marmoset-derived lymphoid cell line, and screened using the human GR cDNA. DNA sequencing determined 76 individual nucleotide substitutions in the coding region of the marmoset GR. Comparison of the marmoset GR nucleotide sequence with the human GR cDNA coding region indicated an overall sequence homology of about 97%. Thirty of the nucleotide substitutions lead to alterations in the predicted amino acid sequence (28 amino acid substitutions) of the marmoset GR. The size of the marmoset GR predicted from the 778 amino acids is approximately 90,000 which is in agreement with previous size estimates of the human and marmoset GRs. Alterations of amino acid sequence in the marmoset GR were greatest towards the amino terminus, including the tau 1 domain putatively involved in transcriptional activation. The DNA-binding domain contained an additional codon (arginine).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930629 TI - Primary structure of hemoglobin alpha-chain from cuckoo (Eudynamys scolopaceae, cuculiformes). AB - The complete amino acid sequence of the alpha A-chain of major hemoglobin component from Cuckoo (Eudynamys scolopaceae) is presented. Separation of the polypeptide subunits was achieved by ion exchange chromatography in the presence of 8 M urea. The sequence was studied by automatic Edman degradation of the native chain and its tryptic fragments in a gas-phase sequencer. Comparison with other avian hemoglobins shows residues alpha 21, alpha 30, alpha 96, alpha 110, and alpha 114 as being specific to Cuckoo. The functional significance of these is discussed. PMID- 1930630 TI - Primary structure of hemoglobin beta-chain from Columba livia (gray wild pigeon). AB - Primary structure of beta-chain of pigeon is presented. It was determined by amino acid sequence analysis of intact beta-chain and its peptides obtained by the enzymatic and chemical cleavage. Comparison of amino acid sequence of the chain with other available data shows beta 14 Ile, beta 61 Lys, and beta 113 Ile as residues specific to pigeon. One important replacement at alpha 1 beta 1 contact is beta 55 Met----Ser. PMID- 1930631 TI - Effect of boronic acids on antifreeze proteins. AB - The activity of antifreeze glycoprotein from the blood serum of Boreagadus saida was strongly inhibited by ions of organic boronic acids as well as by borate. The activity of nonglycoprotein from the blood serum of Pseudopleuronectus americanus, however, was not similarly inhibited. The inhibition by borate is thus specific for molecules with the carbohydrate moiety. PMID- 1930632 TI - Primary structure of Kunitz-type trypsin inhibitor-2a (pI 5.9) from Psophocarpus tetragonolobus (L.) DC seed. AB - The primary structure of acidic trypsin inhibitor-2a (WBTI-2a, pI 5.9) from Psophocarpus tetragonolobus (L.) DC seed was determined. This inhibitor consists of a single polypeptide chain of 180 amino acids including four half-cystine residues and has an N-terminal residue of pyroglutamic acid. The sequence of WBTI 2a, pI 5.9, showed 84% identity to acidic trypsin inhibitor-2 (WBTI-2, pI 5.1) but only 57% identity to the basic trypsin inhibitor (WBTI-1, pI 8.9) and 50% identity to the chymotrypsin inhibitor of winged bean. The data indicate that winged bean seed contains a family of three Kunitz-type inhibitors which have about 50% identity. PMID- 1930633 TI - The binding of anionic and nonionic surfactants to collagen through the hydrophobic effect. AB - The adsorption of nonionic surfactants on hide powder previously treated with anionic surfactants has been studied. The adsorption of nonionic surfactants takes place through hydrophobic interactions. A mechanism has been proposed for this interaction, assuming that the nonionic surfactant has been fixed by means of secondary adsorption (hydrophobic interaction) after the primary adsorption of the anionic surfactant (ionic and hydrophobic interaction) which makes it possible. PMID- 1930634 TI - The complete amino acid sequence of bovine antithrombin (ATIII). AB - Bovine antithrombin (ATIII) is a glycoprotein of Mr 56,600. Its primary structure was established using peptide sequences from five different digests. Bovine ATIII exhibits four glcosylation sites as well as human ATIII. The primary structures of bovine and human ATIII were compared: all the residues required for the integrity of the heparin-binding domain are strictly conserved. However, there are differences in the secondary structures of both proteins, bovine and human ATIII. PMID- 1930636 TI - Distance-constraint approach to higher-order structures of globular proteins with empirically determined distances between amino acid residues. AB - An analysis of higher-order structures of globular proteins by means of a distance-constraint approach is presented. Conformations are generated for each of 21 test proteins of small and medium sizes by optimizing an objective function f = sigma sigma wij(dij - (dij]2, where dij is a distance between residues i and j in a calculated conformation, (dij) is an assigned distance to the (ij) pair of residues which is determined based on the statistics of known three-dimensional structures of 14 proteins in the earlier study, and wij is a weighting factor. (dij) involves information about hydrophobicity and hydrophilicity of each amino acid residue and about connectivity of a polypeptide chain. In these calculations, only the amino acid sequence is used as input data specific to a calculated protein. With respect to higher-order structures regenerated in the optimized conformations, the following properties are analyzed: (a) N14 of a residue, defined as the number of residues surrounding the residue located within a sphere of radius of 14 A; (b) root-mean-square differences of the global and local conformations from the corresponding X-ray conformations; (c) distance profiles in the short and medium ranges; and (d) distance maps. The effects of supplementary information about locations of secondary structures and disulfide bonds are also examined to discuss the potential ability of this methodology to predict the three-dimensional structures of globular proteins. PMID- 1930637 TI - Immunotherapy for recurrent spontaneous abortion and its analogies to treatment for cancer. PMID- 1930635 TI - Spectroscopic, immunochemical, and thermodynamic properties of carboxymethyl(Cys6, Cys127)-hen egg white lysozyme. AB - A three-disulfide form of hen egg white lysozyme with Cys6 and Cys127 blocked by carboxymethyl groups was prepared, purified, and characterized for eventual use in protein folding experiments. Trypsin digestion followed by proline-specific endopeptidase digestion facilitated the unambiguous assignment of the disulfide bond pairings and the modified residues in this derivative. 3SS-lysozyme demonstrated nearly full enzymatic activity at its pH optimum, pH 5.5. The 3SS lysozyme derivative and unmodified lysozyme were shown to be identical by CD spectroscopy at pH 3.6. Immunochemical binding assays demonstrated that the conformation of lysozyme was perturbed predominantly only locally by breaking and blocking the disulfide bond between Cys6 and Cys127. Both 3SS-lysozyme and unmodified lysozyme exhibited reversible thermally induced transitions at pH 2.0, but the Tm of 3SS-lysozyme, 18.9 degrees C, was found to be 34 degrees lower than that of native lysozyme under the same conditions. The conformational chemical potential of the denatured form of unmodified lysozyme was determined from the transition curves to be approximately 6.7 kcal/mol higher than that of the denatured form of 3SS-lysozyme, at pH 2.0 and 35 degrees C, if the conformational chemical potential for the folded forms of both 3SS-lysozyme and unmodified lysozyme is arbitrarily assumed to be 0.0 kcal/mol. A calculation of the increase in the theoretical loop entropy of denatured 3SS-lysozyme resulting from the cleavage of the Cys6-Cys127 disulfide bond, however, yielded a value of only 5.4 kcal/mol for the difference in conformational chemical potential. This suggests that, in addition to the entropic component, there is also an enthalpic contribution to the difference in the conformational chemical potential corresponding to approximately 1.3 kcal/mol. Thus, it is concluded that the reduction and blocking of the disulfide bond between Cys6 and Cys127 destabilizes 3SS-lysozyme relative to unmodified lysozyme predominantly by stabilizing the denatured conformation by increasing its chain entropy. PMID- 1930638 TI - Evidence in support of the plasma membrane as the target for transferrin adriamycin conjugates in K562 cells. AB - We have used transferrin-adriamycin conjugates to deliver drug to transferrin receptors and have shown that the conjugates bind to and kill tumor cells in vivo and in vitro. This has been studied with the use of qualitative and quantitative assays. In this report, we present evidence indicating that the primary target of transferrin-adriamycin cytotoxicity is the plasma membrane. This was done using a spectrofluorometric method that takes advantage of the fluorescence properties of adriamycin. It was shown that, while DNA intercalation may be the primary mechanism of cytotoxicity for free adriamycin, transferrin-adriamycin conjugates were not observed to interact with nuclear DNA. This may be a useful consideration in the design of future chemotherapeutic studies with transferrin conjugates of anticancer drugs. PMID- 1930639 TI - The clinical potential of recombinant human interleukin 4 and alfa-2b interferon. AB - Recombinant human interleukin 4 and alfa-2b interferon (Intron A) exhibit multiple biological effects on cells of diverse origin. Interleukin 4 can affect the growth, differentiation and functional activity of lymphoid and myelomonocytic cells. Alfa-2b interferon expresses a broad spectrum of antiviral, immunomodulatory, and antiproliferative activities. These properties suggest a broad clinical application for both cytokines. PMID- 1930640 TI - Proto-oncogenes in development and cancer. AB - Although analogies are often made comparing development to cancer, there is of course a major difference. Normal development requires complex patterns of rigidly controlled cell proliferation and differentiation. In contrast, cancer represents the pathological condition that results when normal cell growth patterns are uncoupled from their regulatory influences. Genetic studies of RNA tumor viruses have provided insights into the relationships and differences of the genes responsible for normal development and cancer. The presence of discrete genes (oncogenes) within the genome of oncogenic retroviruses is responsible for their tumorigenic potential. Molecular genetic studies have found that normal eukaryotic cells possess genes that are quite homologous to the retroviral oncogenes. These normal cellular genes (proto-oncogenes) are involved in the regulation of proliferation and differentiation. However, if mutated, proto oncogenes have the potential for inducing neoplastic transformation. The conversion of a proto-oncogene to an oncogene is called activation. Proto oncogenes can become activated by a variety of genetic mechanisms including transduction, insertional mutagenesis, amplification, point mutations, and chromosomal translocations. In each instance the genetic aberration results in a proto-oncogene that is now free of its normal regulatory constraints. Such deregulation of function imparts a distinct growth advantage to the cell. PMID- 1930642 TI - Withdrawal. Gene expression of macrophage colony-stimulating factor (M-CSF) and its receptor (c-fms) in human placenta and decidua. PMID- 1930641 TI - Peptide growth factors: the parallel between fetal development and malignant transformation. AB - Normal embryonic development and tissue homeostasis depend upon cell-to-cell and tissue-to-tissue communication. Much of this depends upon the production and release of peptide growth regulators such as fibroblast growth factor, epidermal growth factor, etc. As the molecular basis of malignant transformation has been documented, it is apparent that a common means by which a tumor becomes autonomous of external control is by becoming independent of the need for external growth factor stimulation. This can occur through the cell producing and releasing the growth factors needed for its own growth. A similar end result can occur with growth factor receptor mutants in which the receptor gives a positive signal even when no growth factor is bound to the receptor. One potential therapeutic strategy is to interfere with this autocrine loop. Suramin is presented as an example of a drug capable of blocking such autocrine loops. This drug also reverses malignant transformation due to Platelet Derived Growth Factor and K-fgf/hst oncogenes on this basis. Another potential mechanism to accomplish the same end is through the use of monoclonal antibodies to either the growth factor or its receptor. Examples of this are available for TGF-alpha. We have discussed a range of practical issues involved in developing monoclonal antibodies as therapeutic agents. PMID- 1930643 TI - Analogies between pregnancy and cancer. PMID- 1930644 TI - Occurrence of other reproductive failures among women with recurrent spontaneous abortion. AB - We have previously reported an association between recurrent spontaneous abortion and ectopic pregnancy. We now report that not only ectopic pregnancy, but also other reproductive failures including hydatidiform moles, preterm births, and stillbirths are also associated with recurrent spontaneous abortion. The obstetrical histories of 455 women who had experienced two or more consecutive spontaneous abortions were studied for the occurrence of term births, preterm births, stillbirths, spontaneous abortions, ectopic pregnancies, and hydatidiform moles. The observed frequencies of these reproductive outcomes were compared with the expected frequencies of 920 term births, 80 preterm births, five stillbirths, 150 spontaneous abortions, 14.5 ectopic pregnancies and 0.5 molar pregnancies per 1,000 livebirths. The 455 women had experienced 1,968 pregnancies of which 184 were term births, 30 were preterm births, 16 were stillbirths, 1,669 were spontaneous abortions, 63 were ectopic pregnancies, and six were molar pregnancies. The ratio of observed to expected values was term births 0.1, preterm births 1.6, stillbirths 14.0, spontaneous abortion 6.6, ectopic pregnancy 2.6, and molar pregnancy 7.1. The gravid specific proportions of reproductive outcomes were constant suggesting comorbidity or common cause(s). The commonality that links these types of reproductive failure will provide insight into the mechanisms of reproductive wastage. PMID- 1930646 TI - Current nursing management of an entry-level perioperative nursing course. AB - In response to today's health care environment, the entry-level course in perioperative nursing is continually evaluated and updated. This reflects our ethical and social responsibilities to new nurses in the operating room and our commitment to high-quality patient care. The need for technical knowledge by the professional perioperative nurse is increasing, but the necessity for patient advocacy and holistic care is not superseded by technical considerations. This is what differentiates the professional nurse from the technician. This theme is constantly emphasized during the course. We believe that this entry-level course is a valid response to the need for perioperative nurses. It is cost-effective. It promotes group interaction and peer support during the learning and socialization process, which in turn makes the new nurse more likely to remain employed in the institution's operating room. PMID- 1930645 TI - HIV proteins in normal human placentae. AB - Cryostat sections of human normal term placentae were studied for evidence of immunopathology by using antibodies to lymphocytes, macrophages, platelets, and coagulation factors. Areas of so-called chronic villitis of unestablished etiology were identified in all placentae. The same tissues were examined for HIV protein antigens gp120, p17, p24, and gp41. No evidence for gp41 was found. Antigens gp120 and p17 were identified in normal chorionic villi in vimentin positive fibroblast-like cells and in endothelium, respectively. Antigen p24 was localized to HLA-DR positive cells that morphologically resembled macrophages in areas of villitis. The distribution of gp120 and p17 was similar to that observed for tissue factor. These findings prompted speculation that retroviral proto oncogenes that are known to encode for certain placental receptors could be involved in the presentation of tissue factor, and that gp120 may be a hitherto unrecognized immunobiological mechanism for the blockade of CD4 on maternal lymphocytes if and when such cells gain entrance to chorionic villi. PMID- 1930647 TI - Intensive nursing care after chest wall reconstruction. PMID- 1930648 TI - Precepting in the operating room. PMID- 1930649 TI - Laser surgery and cancer treatment. PMID- 1930650 TI - Support services in the operating room. PMID- 1930651 TI - The Surgical Services Center. PMID- 1930652 TI - The perioperative nurse: continuity of care. PMID- 1930653 TI - Reconstructive surgery for squamous cell carcinoma of the floor of the mouth: a case report. PMID- 1930654 TI - Certification for perioperative nurses. PMID- 1930655 TI - Perioperative nursing in the new decade: what does the future hold? PMID- 1930656 TI - Painful memories. PMID- 1930658 TI - Holding room for the preoperative patient. PMID- 1930657 TI - A glimpse into the past of cancer nursing. PMID- 1930659 TI - Influence of burn-induced lipid-protein complex on IL1 secretion by PBMC in vitro. AB - The lipid-protein complex (LPC) formed by thermal injury to skin, which has been shown to have a toxic effect on mice, and which suppresses the immune response, was tested for its specific influence on monocytes. Growth of bacterial endotoxin stimulated peripheral blood mononuclear cells (PBMC) was inhibited in the presence of LPC, however, the inhibition was less at the time of the optimal rate of cell proliferation. Inhibition was proportional to LPC concentration. ConA stimulated PBMC were also inhibited by LPC in a dose-related manner. PBMC, in the presence of LPC, secreted interleukin 1 (IL1) at an increasing rate as LPC concentration rose from 5 to 40 micrograms/ml, and the levels of IL1 which could be induced by endotoxin were increasingly amplified in the presence of LPC. In comparison to LPC, the native tissue proteins which were isolated from unburned skin by the same techniques which produced LPC from burned skin, were tested for their effect on PBMC. Native proteins had no effect on IL1 secretion, whether on background or endotoxin-stimulated levels. Thus, the thermally induced change in skin proteins has a specific effect on monocyte IL1 secretion which is not matched by the native proteins, indicating that burn injury to skin specifically affects the lymphokine cascade and consequent immune function. PMID- 1930660 TI - Insulin-like growth factor 1 (IGF-1) in burn patients. AB - Variations in growth factor IGF-1 levels during wound healing were assessed in 23 patients with burns of varying extent and severity. The patients were followed during the postburn period and the IGF-1 levels were regularly measured by radioimmunoassay. All patients with large burns had reduced IGF-1 levels which correlated with the surface area of burn. The most plausible reason for the suppressed IGF-1 level in these patients may be diffusion from the burned skin as we have found a strong correlation between IGF-1 and serum albumin. The reduced IGF-1 levels may contribute to impaired wound healing in these patients. PMID- 1930661 TI - Effect of haemolysis on reticuloendothelial system (RES) phagocytic activity in rats. AB - The role of haemolysis of blood in the alterations in the uptake of [99mTc]SC ([99mTc]-sulphur colloid) in vivo in the rat has been examined. When the haemolysed blood (produced by first freezing the blood in liquid nitrogen) was infused into synergenic Lewis rats via the tail vein, there was a significant reduction in the uptake of the [99mTc]SC by the spleen, but lung, liver and kidney uptake remained constant. These results suggest that haemolysis of the blood may play a role in the alterations in RES phagocytic activity observed in the spleen following thermal injury. PMID- 1930662 TI - Soluble interleukin 2-receptor alpha secretion is related to altered interleukin 2 production in thermally injured patients. AB - This study examines the relationship between the capacity for interleukin-2 (IL2) production and the magnitude of the in vitro and in vivo secretion of IL2R alpha in 43 patients with major burns (30-90 per cent total body surface area). Throughout the postburn period a significant (P less than 0.001-0.05) proportion of patients studied demonstrated increasingly high levels of serum IL2 ranging from 2 to over 500 U/mL. Serum IL2R alpha also increased, reaching its highest levels at 15-40 days postburn, while serum IL2 gradually declined. In this period in vitro IL2 production and IL2R alpha secretion in patient's cultures were significantly reduced compared to control. However, in parallel cultures supplemented with exogenous IL2, IL2R alpha levels could be significantly increased (2.5 fold). IL2R alpha levels also approached normal in peripheral blood mononuclear cell cultures from recovering patients whose in vitro IL2 production had improved. These observations suggest that in the burn patient altered synthesis and/or secretion of the soluble form of IL2R alpha may be related to IL2 content. Above physiological levels of IL2R alpha and its ligand in postburn serum also indicate that thermal injury induces strong in vivo activation of the lymphoid system. PMID- 1930663 TI - Hyperbaric oxygen treatment of healthy volunteers with u.v.-irradiated blister wounds. AB - Healthy male volunteers were wounded by skin blistering, excision of the blister roof and u.v.-irradiation of the dermal wound bed. The lesions, painlessly inflicted on one forearm, were occluded, and no systemic therapy was given (n = 7). Ten days later the procedure was repeated contralaterally, and this time hyperbaric oxygen (HBO) therapy was given (1 h at 283 kPa in a 'multi-place' chamber) beginning 1.5 h, 10.5 h and 21.5 h after injury. The maximum 'length' of the lesions - including the surrounding oedema zone - differed throughout the experiment when comparisons were made on a daily basis (P less than 0.005 on day 1). The values were lower after HBO treatment, the difference being maximal on day 1 when it was 41 per cent. The hyperaemia at the periphery of the lesions, assessed with a mechanical laser Doppler linear scanner, was less in the HBO treated group on days 3, 4, and 5 (P less than 0.05 on day 3). Centrally within the wound the mean Doppler values were lower after HBO-treatment for the duration of the experiment, but the differences were not significant for comparisons made on a daily basis. The exudation rates decreased after HBO treatment (P less than 0.05 on days 2-6). The end-points of epithelialization (5.1 days (HBO group) vs. 5.7 days) did not differ significantly. Thus, HBO had beneficial effects on this superficial dermal lesion. Oedema and exudation decreased, as did the peripheral hyperaemia, but the rate of epithelialization was not accelerated. PMID- 1930664 TI - A review of the reconstructive surgery needs of 3167 survivors of burn injury. AB - A retrospective review of all patients admitted for acute care over the past 15 years was undertaken to identify readmission for reconstructive surgery. Of 3167 survivors 629 or 19.9 per cent were readmitted for at least one reconstructive procedure. Those patients requiring readmission for reconstructive surgery were younger and had larger total body surface burns compared to the group that were not readmitted for reconstructive surgery. The percentage of patients now being readmitted for reconstructive surgery is decreasing significantly and covers all size burns. The most common area of reconstruction, by frequency, involved the hand and wrist, arm and forearm, face, and neck. These data indicate that the goal of reducing the incidence of burn scar contractures in this patient population is being achieved. However, further work needs to be done to reduce the frequency of reconstructive surgery and to identify those variables which predispose patients to burn scar contractures which are amenable to intervention. PMID- 1930665 TI - Bonfire and barbecue burns. AB - A 10-year retrospective study of burn injury associated with bonfires and barbecues was undertaken at a regional burns unit. Fifty-four patients were identified and their notes were reviewed. They represented 2.16 per cent of all burn admissions during this period. PMID- 1930666 TI - Microbiological aspects of burns at Mount Vernon Hospital, UK. AB - Bacterial infection in 100 burned patients over a 10-month period has been studied. The commonest colonizing organism was Staph. aureus (69 per cent), followed by E. coli (35 per cent). Pseud. aeruginosa accounted for only 28 per cent of isolates. The role of the different bacterial species in burns pathology is discussed. Group G haemolytic streptococci were isolated from 10 per cent of patients and caused graft failure in some cases. Only 3 per cent of patients developed septicaemia and all were due to Staph. aureus. Our approach to management of infection in burns, especially the policy on systemic antimicrobial chemotherapy, is described. PMID- 1930667 TI - Adhesive contact media--an update on graft fixation and burn scar management. AB - With the introduction of silicone gel in 1981, the emphasis in the treatment of burn scar management has changed from pressure to the use of contact media. A range of 'contact media' has been introduced, allowing for therapy to be individualized to the patient and the scar. Over the last few years, the introduction of 'the adhesive technique' has allowed for earlier therapy with the aim of preventing or minimizing scar hypertrophy with better short- and long-term cosmetic results. The mode of action of 'contact media' is discussed, with a suggested hypothesis and further lines of investigation. PMID- 1930668 TI - The Ural train-gas pipeline catastrophe: the report of the IDF medical corps assistance. AB - Following the destruction of two trains in the Urals 2000 km east of Moscow, as a consequence of the conflagration caused by an explosion from a leaking natural gas pipeline, 3000 people were injured;* most of them (2200) died* immediately and the others (about 800) were badly burned. At the request of the Soviet Union Government a medical military delegation was sent to give assistance to the injured people. This report describes the treatment given by the delegation to 40 patients with burns of between 40 and 90 per cent TBSA during a period of 10 days. An insight into a Soviet Union Trauma Center is given and the good treatment given by the Soviet colleagues is emphasized. PMID- 1930669 TI - Evaluation of boiled potato peel as a wound dressing. AB - In a series of experiments full thickness skin defects in 68 rats were covered with dressings made of boiled potato peels according to the method developed in Bombay. The wounds closed within 14 days and histologically complete repair of epidermis was found. The cork layer of the potato peel prevents dehydration of the wound and protects against exogenous agents. Experiments with homogenates revealed that a complete structure of the peel is necessary. Steroidal glycosides may have contributed to the favourable results. PMID- 1930670 TI - The evolution of burn treatment in the last 50 years. PMID- 1930671 TI - Ritual burns--the Buddhist tradition. AB - The mystical significance of fire is common to many cultures and religions. For the Buddhist community acts of self-mutilation by burning reflect a tradition for which the direct precedent is set in the ancient scriptures of the Lotus Sutra. Burns are produced by contact with incense and treated with oil and vegetable dressings. Two cases are presented and discussed with reference to early Buddhist beliefs. PMID- 1930672 TI - Electrical burn injury of the scalp--bone regrowth following application of latissimus dorsi free flap to the area. AB - A large defect of the scalp was observed soon after debridement of a high-tension electrical burn of the scalp. Bone scan revealed no uptake of radioactive material to the parietal bone below the necrotic tissue of the scalp. Consecutive bone scans after latissimus dorsi free flap transfer revealed progressive regrowth of the bone. PMID- 1930673 TI - Pyogenic pericarditis in a patient with burns--a rare complication. AB - We report a patient with 60 per cent of the body surface area burned who developed pyogenic pericarditis which was treated successfully by open pericardial drain. In an estimated 1000 patients with burns treated in this hospital over a period of 5 years from 1984 to 1989, this is the first patient developing pyogenic pericarditis. A possible pathological basis for the sequence of events is discussed. PMID- 1930674 TI - Use of buried skin implants after recurrent failure of conventional skin grafting in a massive burn: the renewal of an old technique. AB - The technique of burying small pieces of skin under old granulation tissue after recurrent failure of conventional skin grafting is described in a patient with 95 per cent full skin thickness burns. This method of treatment, which was described in the past and neglected, is of value for massive burns or grafting in difficult areas. The technique is described again and the relevant literature reviewed. PMID- 1930675 TI - Pore-forming bacterial protein hemolysins (cytolysins). AB - Protein toxins forming pores in biological membranes occur frequently in Gram positive and Gram-negative bacteria. They kill either bacteria or eukaryotic cells (at most, a few seem to act on both groups of organisms). Most of the toxins affecting eukaryotes have clearly been shown to be related to the pathogenicity of the producing organisms. Toxin formation frequently involves a number of genes which encode the toxin polypeptide as well as proteins for toxin activation and secretion. Regulation of toxin production is usually coupled with that of the synthesis of a number of other virulence factors. Iron is the only known environmental factor that regulates transcription of a number of toxin genes by a Fur repressor-type mechanism, as has been originally described in Escherichia coli. Interestingly, the thiol-activated hemolysins (cytolysins) of Gram-positive bacteria contain a single cysteine which can be replaced by alanine without affecting the cytolytic activity. The Gram-negative hemolysins (cytolysins) are usually synthesized as precursor proteins, then covalently modified to yield an active hemolysin and secreted via specific export systems, which differ for various types of hemolysins. PMID- 1930676 TI - Basic and applied aspects of microbial adhesion at the hydrocarbon:water interface. AB - Microbial hydrophobicity has been studied since 1924. During the last decade, various techniques have become available for measuring hydrophobic surface properties of microbial cells. This has led to a surge in investigations suggesting a role for hydrophobicity in adhesion of bacteria to an array of surfaces (oral surfaces, mineral particles, fatty meat, epithelial cells, phagocytes, biomaterials), partitioning at interfaces, as well as gliding mobility. The present manuscript comprises a critical, chronological look at the origins of microbial hydrophobicity research, its development, origins, and applications. Emphasis is placed on microbial adhesion to hydrocarbons, a technique with which the author has the most experience and research interest. PMID- 1930677 TI - Virulence, immunity, and vaccine related to Streptococcus pneumoniae. AB - The pathogenesis of bacterial infection involves a series of interactions between the virulence determinants of the microorganisms and the immunity of the host. Studies on the molecular structure and immunological properties of pneumococcal virulence factors have provided general knowledge for the chemical basis of immunogenicity and prevention of bacterial infection. Antibody responses to PS and protein antigens can be greatly affected by their physicochemical properties, e.g., molecular size, specific determinants, conformation, etc. Characterization of group 19 pneumolysins and cloning of their ply genes were studied to examine the relationship of ply to virulence. Group 19 pneumococci all contained ply; the disease-isolated types of 19F and 19A appeared to show a higher specific hemolytic activity and yield than the nonpathogenic types, 19B and 19C. Genomic DNA that contained the ply gene from group 19 strains were analyzed by the polymerase chain reaction (PCR). Type 2 oligonucleotide primers recognized and initiated synthesis of an identical 1.5 kb DNA fragment in types 2, 19F, 19A, 19B, and 19C. Their sizes of restriction DNA fragments were also found to be homologous. Thus, group 19 ply genes showed remarkably similar characteristics. A difficult problem in the development of vaccines against bacterial diseases is the poor immune response of young children to purified PSs. The efficacy of pneumococcal vaccine might be improved by supplementation with inactivated pneumolysin in the form of a PS-protein conjugate. PMID- 1930678 TI - Blood lactate: biochemistry, laboratory methods, and clinical interpretation. AB - With the renewed awareness of blood lactate as an indicator of circulatory impairment, there has been much interest in the use of lactate measurements to determine the overall state of oxygenation of patients in critical care. This review begins by covering the areas of lactate homeostasis and biochemistry, both of which are essential for fully understanding the interpretation of lactate measurements. Then, the clinical interpretation of lactate measurements includes sections on the causes and treatments of hemodynamic deficits leading to lactic acidosis, the classification of lactate abnormalities, and the use of lactate measurements in critical care monitoring, including surgery. Both the principles and the latest developments in lactate methodology are covered, including the new whole blood analyzers. This review concludes with reference intervals and guidelines to the interpretation of results. PMID- 1930679 TI - Overview of radiopharmaceuticals for diagnosis of central nervous disorders. AB - There are two types of imaging instruments, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) that use radiopharmaceuticals for the diagnosis of brain disorders. Brain perfusion imaging agents, labeled either with 123I or 99mTc, are useful in detecting various cerebral vascular abnormalities, such as stroke and transient ischemia with SPECT. The management of other neurological disorders (i.e., in Alzheimer's, epilepsy, schizophrenia, and head trauma patients) may also be benefitted by these agents. The exact trapping mechanisms and their relationships with potential clinical applications still remain to be elucidated. Imaging studies using 18F fluorodeoxyglucose with PET is currently the most promising diagnostic tool for the evaluation of local glucose metabolism related to various disease states, such as Alzheimer's disease, brain tumor, and epilepsy. In the past few years significant progress has been made in the design and characterization of new CNS neuronal and postsynaptic receptor imaging agents for PET and SPECT. The new diagnostic agents are aimed at measurements of localization and changes of neuronal function. It is likely that these types of agents have potential for clinical application, especially in the diagnosis of psychiatric disorders that do not involve morphological changes. PMID- 1930681 TI - Sucrose and delinquent behavior: coincidence or consequence? AB - Over the past decade, a number of theories have appeared that are attempts to relate consumption of simple sugars to violent or delinquent behavior. Such claims have been based mainly on anecdotal reports, misinterpretations of scientific literature, or flawed interpretation of questionable data. Thus, these claims remain unsubstantiated. There are data that suggest that a very few individual hyperactive children may respond adversely to a sucrose challenge, but most carefully designed and controlled studies with children offer no convincing evidence that sucrose ingestion exacerbates hyperkinetic behavior. While provocative evidence is beginning to emerge from studies of incarcerated juvenile delinquents, as well as from studies of adult criminals habitually violent under the influence of alcohol, that anomalies in carbohydrate metabolism may in some way be related to expression of antisocial behavior, there is no evidence to suggest that consuming sucrose causes violent behavior. On the contrary, ingestion of foods that contain simple carbohydrates may elicit beneficial responses, at least in behavioral subgroups of adolescent males. PMID- 1930680 TI - Osteocalcin: diagnostic methods and clinical applications. AB - Osteocalcin is a small (Mr 5800), very interesting bone specific protein, synthesized by osteoblasts and measured in plasma as a biochemical indicator of bone formation. Many immunoassays for osteocalcin have been developed, including radio- and enzymoimmunoassays, with the use of monoclonal and polyclonal antibodies. These are used in many different clinical settings, including bone, kidney, and liver diseases. However, there is a wide range of published values for plasma osteocalcin concentrations in control and patient samples and this has hindered a more widespread adoption of osteocalcin measurement by clinicians. This review discusses how various immunoassays for osteocalcin may contribute to the wide variation of published values and suggests approaches for the development of standardized assays. For example, epitope specificity and immunoreactivity with multiple forms of osteocalcin and osteocalcin peptides in plasma are discussed. It also includes a recent update on interesting clinical applications of osteocalcin. PMID- 1930682 TI - Sugar crystallization in food products. AB - A review of the recent literature on crystallization of the commercial sugars (fructose, glucose, lactose, and sucrose) is presented. Topics include: NUCLEATION--The formation of the crystalline phase from supersaturated solutions can occur by either a spontaneous or a forced nucleation mechanism. Recent work on the mechanisms, kinetics, and impact of both heterogeneous and secondary (contact) nucleation is discussed. GROWTH--Recent studies on the mechanisms and kinetics of crystal growth will be reviewed. This discussion includes work on the growth rate dispersion exhibited by these sugars. EFFECTS OF IMPURITIES AND ADDITIVES--The presence of impurities and additives (including mixed sugar systems) affects both the nucleation and growth steps. A discussion of the recent work in this area is included. Emphasis is placed on the relationship between these crystallization phenomena and the solution structure for comparison purposes. PMID- 1930684 TI - Transcriptional regulation of the HLA-DRA gene. AB - Class II Major Histocompatibility Complex (MHC) products are essential initiators of cellular immune responses. Their cell surface expression demonstrates aspects of tissue-restricted, inducible, differentiation-dependent, and coordinate regulation indicative of complex molecular controls mediated primarily at the level of transcription. This article reviews our current understanding of transcriptional regulation of one such human class II MHC gene, DRA. Considerable effort has been exerted toward characterizing the cis-acting regulatory sequences and trans-acting DNA binding proteins responsible for regulating DRA transcription. Recent application of novel molecular techniques has resulted in the cloning and characterization of some of these regulatory proteins. A model is presented herein which accommodates the current knowledge of DRA gene regulation. PMID- 1930683 TI - The B-G multigene family of the chicken major histocompatibility complex. PMID- 1930685 TI - MR of infectious and inflammatory diseases of the spine. AB - Magnetic resonance imaging is the study of choice in the evaluation of infectious and inflammatory disease of the spinal cord and spinal column. Not only is the multiplanar imaging a distinct advantage over other modalities, but direct visualization of the soft tissues, including the spinal cord, paraspinal musculature, and disk, is present. The sensitivity of MR, to evaluate infectious processes of the spine, especially when used with gadolinium, has been well documented. This article is an overview of the pathophysiology and MR appearance of various types of inflammation and infection of the spine. Subjects covered include disk space infections, epidural abscess, meningitis, arachnoiditis, and inflammatory mimics of disk space infections. Suggested imaging protocols are stated. PMID- 1930686 TI - Radiography of acromioclavicular dislocation and associated injuries. AB - The superficial location of the acromioclavicular joints in the human skeleton makes it vulnerable to several kinds of disruptive forces, resulting in a variety of injuries. In this review, we describe different types of acromioclavicular dislocation and associated fractures. We emphasize the radiographic features and methods of detecting the lesions otherwise unnoticed along with the mechanisms, the frequency, and the pathology of the injuries. PMID- 1930687 TI - Acute abdominal disorders in AIDS: CT evaluation. PMID- 1930688 TI - Human genes other than CD4 facilitate HIV-1 infection of murine cells. AB - The human CD4 glycoprotein is a specific receptor for the HIV family of retroviruses. When expressed on human cell lines, this molecule binds virus through direct interactions with the gp 120 viral envelope glycoprotein thus allowing virus infection to occur. Subsequent to binding, conformational changes in the viral envelope glycoproteins are thought to facilitate virus entry into the target cell through direct fusion of the virus with the cell membrane. In contrast to the infection observed in human cell lines, infection of murine cell lines even in the presence of the CD4 receptor does not readily occur. We have examined this species tropism of HIV infection. We report that the inability to infect murine cells is not a function of the receptor for HIV or a suppressive function of the murine cellular background. Human CD4 expression, configuration and down-modulation on the murine background are similar if not identical to expression on the human cell background. Utilizing a panel of interspecific cell hybridomas, we have been able to bypass the barrier to infectivity of human CD4 positive murine cells. We demonstrate that there are at least two different restrictions to infectivity on the mouse background which can be complemented by the human genome. One restriction appears to be an extremely early postbinding function likely to be molecules necessary for viral entry into cells, the second restriction is necessary for high levels of virus production. Our mapping studies suggest that fewer than five human chromosomes are necessary for reconstituting infectivity in the murine background. These results have implications for models of HIV-induced pathogenesis and infectivity. PMID- 1930689 TI - Cytokine administration alters the distribution of activated lymphocytes to the lung. AB - The effects of intraperitoneal injections of recombinant interleukin-1 alpha (IL 1; 250,000 U/day), interleukin-2 (IL-2; 50,000 units/day), interferon-gamma (IFN gamma; 50,000 U/day) and tumor necrosis factor-alpha (TNF; 100,000 U/day), on the biodistribution of concanavalin A (Con A)-activated, indium-111-labeled lymphocytes were evaluated in BALB/c mice. Syngeneic spleen cells were activated for 48 h in medium with Con A (5 micrograms/ml) and maintained in culture for 72 h in IL-2 (1,000 U/ml). Groups of 12 mice were treated for 4 days with either one of the cytokines or saline. On day 4, mice received 10(7) lymphocytes (3-5 mu Ci) intravenously. Mice were sacrificed at 4 and 24 h following injection and the percent of administered dose per organ was determined. TNF and IL-1 produced a significant increase in lung uptake of radiolabeled lymphocytes at 4 and 24 h, whereas IL-2 and IFN-gamma decreased uptake at both time points. IL-1 increased uptake by liver at 4 and 24 h while IL-2 increased uptake only at 4 h. We conclude that the distribution of activated lymphocytes following adoptive transfer is altered by cytokines. This finding may have important implications for cell delivery during adoptive immunotherapy. PMID- 1930690 TI - Modulation of endotoxic activity of lipopolysaccharide by high-density lipoprotein. AB - Unlike agonists such as cytokines or hormones, the biological activity of bacterial lipopolysaccharide (LPS) is substantially modified by serum proteins. One such interaction in serum is with high-density lipoprotein (HDL) forming LPS HDL complexes. LPS-HDL complexes have been previously shown to have reduced endotoxic activity, for example pyrogenicity, when compared to other forms of LPS in animal models. In this study, we report results of studies comparing the potency of LPS-HDL complexes with uncomplexed LPS as agonists for interleukin-1 (IL-1) production by two different sources of monocytes. LPS-HDL complexes were purified by ultracentrifugation in sodium bromide gradients. The human monocytic cell line THP-1 and the freshly isolated human monocytes, purified by adherence or elutriation from venous blood from healthy donors, were exposed to medium alone containing 1 mg/ml bovine serum albumin, HDL, LPS (parent LPS) and LPS-HDL complexes. mRNA level was analyzed on Northern blot, and cell-associated protein and supernatants were tested for IL-1 production using immunologic and biologic assays. LPS stimulates substantially more IL-1 mRNA and cell-associated IL-1 protein when the monocytes are stimulated with LPS alone versus LPS-HDL. These data suggest that LPS-HDL complexation may contribute to a reduction in endotoxic activities in vivo by preventing LPS (lipid A) from generating important transmembrane signals after binding to cells. PMID- 1930691 TI - Identification of two 36-kD phosphoproteins associated with altered differentiation in retrovirus-transformed Balb/MK-2 mouse keratinocytes. AB - Balb/MK-2 cells, derived from mouse epidermal keratinocytes, require epidermal growth factor (EGF) for growth and undergo terminal differentiation when exposed to extracellular calcium levels greater than 1.0 mM. Transformation of these cells by a variety of acute transforming viruses abrogates the EGF requirement and blocks terminal differentiation. In general, oncogenes coding for tyrosine kinase oncoproteins abolish differentiation at an earlier step than those of the ras gene family. We therefore examined whether alterations in protein phosphorylation occur during differentiation of the Balb/MK-2 cells and two different viral transformants. Only one 36-kD phosphoprotein emerged whose phosphorylation consistently changed during epidermal differentiation. Modifications in the phosphorylation of a second 36-kD protein occurred in the virally transformed cell lines. Phosphoamino acid analysis of the proteins demonstrated only the presence of phosphoserine residues. These studies define changes in protein phosphorylation associated with the regulation of epidermal differentiation. PMID- 1930692 TI - Suppression of human immunoglobulin synthesis by interleukin-4 in tandem with interleukin-2 through large granular lymphocytes. AB - Recent studies have shown that interleukin (IL)-4 can affect secretion of immunoglobulins (Igs) or activation of cytotoxic cells by IL-2, while other studies have shown that natural killer (NK) cells/large granular lymphocytes (LGLs) can also affect Ig synthesis. Therefore, we examined the effect of IL-4 with and without IL-2 or human NK/LGLs on pokeweed mitogen (PWM)-stimulated production of IgM and IgG. We found that when IL-4 and/or IL-2 were incubated with peripheral blood lymphocytes and PWM for 7 days and an enzyme-linked immunosorbent assay was run to measure Ig synthesis, IL-4 with IL-2 caused a greater suppression of Ig synthesis than either cytokine alone. A further experiment was done to determine the effect IL-4 and IL-2 would have on LGL suppression of Ig synthesis. IL-4 and IL-2 alone and in combination, when added to LGL, caused the LGL to suppress Ig synthesis to a greater extent than alone. We conclude that IL-4 acts on NK/LGLs separately and jointly with IL-2, to suppress Ig synthesis (IgM and IgG). PMID- 1930693 TI - A human putative lymphocyte G0/G1 switch gene containing a CpG-rich island encodes a small basic protein with the potential to be phosphorylated. AB - Genes actively involved in the G0/G1 switch (G0S genes) may be differentially expressed during the lectin-induced switch of lymphocytes from the G0 to the G1 phases of the cell cycle. This paper presents studies of G0S2, a member of a set of putative G0S genes, for which cDNAs were cloned and selected on the basis of differential cDNA hybridization. G0S2 mRNA increases transiently within 1-2 hr of the addition of lectin or cycloheximide to cultured blood mononuclear cells. Comparison of a nearly full-length cDNA sequence with the corresponding genomic sequence reveals one small intron and an open reading frame in the second exon. The derived 103-amino-acid basic protein has two potential alpha-helical domains separated by a hydrophobic region with the potential to generate turns and assume a beta-sheet conformation. Consistent with involvement in the G0/G1 switch, the protein contains potential sites for phosphorylation by protein kinase C and casein kinase II. The gene contains a CpG-rich island suggesting expression in the germ line. An upstream segment contains tandem dinucleotide repeats (CT)19/(CA)16. There is a suitably located TATA box, but potential sites for CCAAT-box binding factors are far upstream, embedded in a 42-nucleotide repeat element. Potential sites for transcription factors AP1, AP2, and AP3 are consistent with rapid transcriptional activation in response to inducing agents. PMID- 1930694 TI - The gene encoding ovine follicle-stimulating hormone beta: isolation, characterization, and comparison to a related ovine genomic sequence. AB - Follicle-stimulating hormone (FSH), the primary stimulus for egg and sperm maturation in mammals, is an alpha/beta heterodimer. Each subunit is encoded by a single-copy gene in the human, bovine, and rat genomes. Transcription of both subunits is inhibited by estradiol and progesterone in ovine pituitary cultures. We report the sequence of one ovine FSH-beta gene (-1,527 to +3,664) that is expressed in vivo and the identification of a novel, second ovine FSH-beta-like sequence. Digestion of ovine genomic DNA with Bgl II yielded two fragments of 10 kb and 15 kb that hybridized to a bovine FSH-beta cDNA. The 10-kb fragment contained 6 kb of 5'-flanking region and all but about 200 bp of the 3' terminus of the ovine FSH-beta gene. This FSH-beta gene encodes a protein that differs from the published ovine protein sequence only at the carboxy terminus (Arg 109Glu-110[STOP codon] instead of Glu-109Arg-110[Glx-111]) and at positions 49 (Ala instead of Thr) and 88 (Arg instead of Ser). This gene is organized similarly to the human, bovine, porcine, and rat FSH-beta genes, and its coding sequence is nearly identical (99.5%) to a reported ovine FSH-beta cDNA. Expression of the FSH-beta gene on the 10-kb fragment in vivo was determined by analysis of wether mRNA using the polymerase chain reaction. A 95-bp sequence of the 15-kb fragment was 87% homologous to the corresponding coding region of the 10-kb fragment. This comparison suggested that the 15-kb fragment contains either an FSH-beta-like sequence or a pseudogene. Several potential steroid response elements were found by sequence analysis of the 5'-flanking region of the FSH beta gene on the 10-kb fragment. A mechanism by which these elements may act is suggested. PMID- 1930695 TI - Molecular cloning and characterization of the Caenorhabditis elegans elongation factor 2 gene (eft-2). AB - A Caenorhabditis elegans lambda ZAP cDNA library was screened using a fragment amplified from highly conserved regions of the mammalian and Drosophila elongation factor 2 (EF-2). Two types of cDNA clones were obtained, corresponding to two mRNA species with 3'-untranslated regions of 60 and 115 nucleotides, both encoding identical polypeptides. Sequence analysis of these clones and comparisons with hamster and Drosophila EF-2 sequences suggests that they encode C. elegans EF-2. Clone pCef6A, encoding the entire C. elegans EF-2 mRNA sequence including 45 nucleotides of 5'-untranslated region, contains a 2,556-bp open reading frame which predicts a polypeptide of 852 amino acid residues (Mr 94,564). The deduced amino acid sequence is greater than 80% identical to that of mammalian and Drosophila EF-2. Conserved sequence segments shared among a variety of GTP-binding proteins are found in the amino-terminal region. The carboxy terminal half contains segments unique to EF-2 and its prokaryotic homolog, EF-G, as well as the histidyl residue which is ADP-ribosylated by diphtheria toxin. The C. elegans protein contains a 12-amino-acid insertion between positions 90 and 100, and a 13-amino-acid deletion between positions 237 and 260, relative to hamster EF-2. Partial sequencing of a genomic clone encoding the entire C. elegans EF-2 gene (named eft-2) has so far revealed two introns of 48 and 44 bp following codons Gln-191 and Gln-250, respectively. Southern and Northern blot analyses indicate that eft-2 is a single-copy gene and encodes a 3-kb mRNA species which is present throughout nematode development. PMID- 1930696 TI - Expression of bovine adrenodoxin and NADPH-adrenodoxin reductase cDNAs in Saccharomyces cerevisiae. AB - Expression of both bovine adrenodoxin (ADX) and NADPH-adrenodoxin reductase (ADR) were examined in Saccharomyces cerevisiae. Three ADX and two ADR expression plasmids were constructed by inserting each of the corresponding cDNA fragments between the yeast alcohol dehydrogenase I promoter and terminator of the expression vector pAAH5N. Plasmids pAX and pMX contained the coding region for the precursor and mature ADX, respectively, while pCMX carried the mature ADX preceded by the mitochondrial signal of yeast cytochrome c oxidase subunit IV (COX IV). Similarly, pMR and pCMR coded for mature ADR without and with the mitochondrial signal of yeast COX IV, respectively. Transformed S. cerevisiae AH22[rho 0]/pAX cells produced the ADX precursor, while AH22[rho 0]/pMX and AH22[rho 0]/pCMX cells produced mature ADX (mat-ADX) and modified ADX (mat COX/ADX), respectively. Mat-ADX and mat-COX/ADX were found mainly in the cytosolic and mitochondrial fractions, respectively, and showed cytochrome c reductase activity. AH22[rho+]/pMR and AH22[rho+]/pCMR cells produced mature ADR (mat-ADR) and modified ADR (mat-COX/ADR), respectively. Mat-ADR lacking the mitochondrial signal was found in the cytosolic fraction and exhibited cytochrome c reductase activity, while mat-COX/ADR was localized in the mitochondrial fraction, but showed no reductase activity. In an in vitro reconstituted system consisting of both mat-COX/ADX- and mat-ADR-containing fractions, bovine P450scc converted cholesterol into pregnenolone. Thus mat-COX/ADX and mat-ADR produced in the yeast can transfer electrons from NADPH to P450scc. PMID- 1930697 TI - Clinical evaluation of the Plak Trac toothbrush. AB - Three separate studies have been conducted to evaluate the clinical safety and efficacy of the Plak Trac mechanical toothbrush. In an exaggerated use study, volunteers used the product a minimum of five times a day for eight days. Soft tissue evaluations were conducted before and at various times after use of the Plak Trac brush throughout the study. No tissue irritation related to product use was observed or reported at any time in the study. In a thirty-day at-home use study the Plak Track brush was compared to the Colgate ADA-approved manual toothbrush. Plak Trac was consistently more effective than the Colgate brush on plaque removal, at higher statistical levels. Both brushes were effective in decreasing the gingival index during the study. In a one-time use test, Plak Trac, Interplak, and the Oral B 35 manual brush were evaluated for plaque removal efficacy. All brushes significantly reduced both smooth surface and interproximal plaque scores. On total smooth surfaces Plak Trac was significantly more effective than the Interplak brush. PMID- 1930698 TI - The effect of A Triclosan/copolymer/fluoride dentifrice on plaque formation and gingivitis: a six-month clinical study. AB - A total of 108 adult male and female subjects completed a six-month, double-blind clinical study designed to compare the effect of a dentifrice containing 0.3% triclosan and 2.0% of a copolymer of methoxyethylene and maleic acid (Gantrez copolymer) in a 0.243% sodium fluoride/silica base to a 0.243% sodium fluoride/silica placebo dentifrice on supragingival plaque formation and gingivitis. Subjects were stratified into two balanced groups by their baseline plaque and gingivitis scores. They received an oral prophylaxis and were assigned to use either the triclosan/copolymer dentifrice or the placebo dentifrice for the next six months. After six months, the dentifrice containing triclosan/copolymer provided a 24.93% statistically significant (99% level of confidence) reduction in supragingival plaque, and a 19.72% statistically significant (99% level of confidence) reduction in gingivitis compared to the placebo dentifrice. Twice daily use of a dentifrice containing 0.3% triclosan, 2.0% of a copolymer, and 0.243% sodium fluoride in a silica base, over a six month period, reduces supragingival plaque formation and gingivitis to a significant degree compared to a sodium fluoride/silica base placebo dentifrice. PMID- 1930699 TI - The analgesic efficacy of flurbiprofen compared to acetaminophen with codeine. AB - In a single-dose, parallel group, randomized block treatment allocation study, the relative analgesic efficacy of flurbiprofen, a nonsteroidal antiinflammatory drug, was compared to acetaminophen 650 mg with codeine 60 mg, zomepirac sodium 100 mg, and placebo. A total of 226 post-surgical dental patients (146 females and 80 males) participated in the study. Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination. The results of this study support previous work on flurbiprofen. PMID- 1930700 TI - The influence of herbal ingredients on the plaque index and bleeding tendency of the gingiva. AB - The effectiveness of medicinal herbs in both a toothpaste and oral rinse on dental plaque, sulcus bleeding, and the pH of total saliva was investigated in a single-blind study on 50 dentistry students between the ages of 23 and 28 years. Over a period of 4 weeks, 25 students used either placebo or preparations containing medicinal herbs. Parameters measured were the approximal plaque index (API) and sulcus bleeding index (SBI). These were determined at the same time of day (12:00 P.M.), the last food intake having occurred at least 1 hour previously. Compared with the placebo preparations, the herbal ingredients significantly reduced both the API (initial value: 40.8%, final value: 23.9%) and the SBI (initial value: 33.4%, final value: 18.6%). The pH of the total saliva was significantly displaced into the alkaline range by the application of the herbal products, whereas the placebo products had a contrary effect. The results of this study suggest that herbal ingredients can be employed supportively in the therapy of periodontal diseases and for routine prophylaxis. PMID- 1930701 TI - Gas chromatographic method for trapping and detection of volatile organic compounds from human mouth air. AB - The present investigation describes a convenient method for collection and analysis of volatile organic compounds from 25 ml mouth air samples. Tenax-GC trapping devices coated with Teflon are used to adsorb and concentrate volatile organic compounds in mouth air at -20 degrees C, which are then thermally desorbed at 140 degrees C. Gas chromatography (GC) analyses are performed using an aluminum column coated with Teflon and packed with 2% poly-MPE on 80/100 mesh Tenax-GC, and employing a flame ionization detector. This procedure allows for amplification of peak heights and detection of compounds that may otherwise escape direct analysis. Of the six prominent peaks detected, identification based on retention times indicates the presence of methanol, acetaldehyde, ethanol and acetone. Volatiles collected using this procedure can be maintained at -20 degrees C for up to 48 hours before analysis. The compact sample tubes allow the system to be easily portable, particularly suitable for sampling breath of persons with localized oral or systemic diseases at locations away from the laboratory. The superiority of this method is that relatively small samples are required for analysis, unlike previously published methods which are based on collection of large volumes of expired air in plastic bags. PMID- 1930702 TI - [Nursing care plan out of favor?]. PMID- 1930703 TI - [Nurses on aggression. The NMV survey (Dutch Nursing Association)]. PMID- 1930704 TI - [Hospital de Heel in Zaandam. Home philosophy as basis]. PMID- 1930705 TI - [Tracheotomy--guidelines for nursing technology (1)]. PMID- 1930706 TI - [Tracheotomy--guidelines for nursing technology (2)]. PMID- 1930707 TI - [Who appreciates the kitchen in a hospital? Diet in different cultures]. PMID- 1930708 TI - [Alternative treatment in rheumatoid arthritis. Patients' opinions about it]. PMID- 1930709 TI - [Victims of traumatic events. Management of psychological trauma in the emergency department]. PMID- 1930710 TI - [About/under hypnosis]. PMID- 1930711 TI - Immunohistochemical diagnosis of lymphoproliferative diseases. PMID- 1930712 TI - [Campylobacter jejuni: reflections on enteric infection among Mexican children]. PMID- 1930713 TI - [Campylobacter jejuni infection in children of a rural community]. AB - Colonization of the intestine with Campylobacter jejuni was followed longitudinally from birth in a cohort of 75 rural children with fecal cultures taken every fortnight and every time they had diarrhea. Only 25% of children initially colonized with C. jejuni during the first year of life, and 12% of children initially colonized during the second had diarrhea. The age at which a child was initially infected with C. jejuni was not a risk factor in relation with presence of disease. A higher illness-to-infection ratio (P less than 0.05) was found during subsequent colonization with C. jejuni when initial infection was associated with diarrhea. Risk of diarrhea during initial or subsequent colonization with C. jejuni was not related with the production of cholera-like enterotoxin, a cytotoxic active on HeLa cells or with adhesive ability to HEp-2 cells by the infecting strains. PMID- 1930714 TI - [Thrombocytopenic purpura and hemolytic anemia in children with generalized lupus erythematosus]. AB - We studied 30 children with systemic lupus erythematosus in order to detect the clinical, pathological and serological findings associated with the development of thrombocytopenic purpura and hemolytic anemia. A group of 13 of the 30 children revealed hematological manifestations as the most prominent changes of SLE. Thrombocytopenic purpura and hemolytic anemia were the beginning manifestation of SLE in 11 children. Different causes, for these hematological changes such as hypersplenism, renal microangiopathy or drugs reactions were excluded by history and examination. Interestingly, other immunohematological manifestations including splenomegaly and lymphadenopathy were more frequent in children with thrombocytopenic purpura and hemolytic anemia, than in those patients without these hematological complications. Positive antiplatelet antibodies were found in 4/6 children with thrombocytopenia and 2/5 with hemolytic anemia. A relation of antiplatelet with anticardiolipin antibodies occurred in 4 patients; 3 of them in children with thrombocytopenic purpura and one with hemolytic anemia. Anti-dsDNA and anti-Sm antibodies were positive in almost all patients. Four children shown a transition from anti-dsDNA to anti-Sm antibodies or viceversa and all of them revealed a significant variation in the titer of these antibodies by ELISA, in relation with disease activity. The presence of hematological manifestations associated with anti-platelet and anti cardiolipin antibodies in children with SLE support that different mechanisms triggers autoimmunity in childhood. PMID- 1930715 TI - [Emergency management of convulsions and prevention of status epilepticus with rectal diazepam administered by parents]. AB - The parents of 17 children with a history of convulsions, were shown how to administer liquid diazepam through the rectum using a 1 mL insulin syringe, in order to alleviate a convulsion at home or any where ever this may occur. Eight of the children had suffered from repetitive and/or prolonged non-temperature related convulsions, four had epileptic status and five had suffered from simple fever related convulsions, complicated in four and in a convulsive status in 1; the number of fever-related convulsions ranged between 1 and 6 per child and those non temperature related ranged from one daily to once a month. The observation of the children was done in an 88 month period (between 1 and nine months per child, averaging 5.2 months). In seven of the children, it was required of the parents to administer rectal diazepam a total of 90 times (fluctuating between 2 and 25 doses per child), with no complications, a dose of 0.5 mg/kg was administered in those patients whose convulsions lasted over 5 minutes or more. In 75 occasions, the convulsion stopped within a period of 2 to 5 minutes, in 12 other times there was a need for repeated dosages and in 2 occasions, a third doses was needed. Only in one occasion was hospital management needed. Therefore, we conclude that the administration of rectal diazepam by parents--at home--is a useful and secure method to prevent prolonged convulsions and the epileptic status; it gives parents security and tranquility using an instrument which can be used in any circumstance therefore reducing anguish and the cost of hospital care.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930717 TI - [Nephrotic syndrome in children. Retrospective study at a concentration hospital]. AB - In order to evaluate the usefulness of certain clinical and paraclinical characteristics to be able to discriminate the minimal change disease (MCD) from other histopathological lesions associated with the nephrotic syndrome (NS), the clinical charts of 31 patients were reviewed and relevant data were analyzed. Those patients with no history of biopsy and those with documented MCD through biopsy, were placed in one group (MCD = 25) and the rest as others (others = 6). None of the clinical or paraclinical indicators analyzed showed significant differences between either group. In the MCD group, 76% of the patients entered remission after receiving steroid treatment, while none of the others entered remission. The magnitude of the proteinuria, hypoalbuminemia, hypercholesterolemia, and the presence of hematuria, hypertension or hyperazoemia, were not useful to discriminate those with MCD from other lesions. The response to treatment with prednisone was the most useful data to differentiate the groups. PMID- 1930716 TI - [Fast intravenous rehydration with 90 mmol/L of sodium in dehydrated children with diarrhea]. AB - Twenty-two infants with moderate dehydration due to diarrhea in whom oral rehydration therapy (ORT) was contraindicated or who failed to respond to this method of therapy were treated with rapid intravenous rehydration (RIR). Clinical signs of dehydration without shock allowed us to estimate 5% to 10% of weight loss. Patients were 11 days to 19 months old, and 9 of them were undernourished. A standard solution containing 90 mmol/L sodium, 80 mmol/L chloride, 30 mmol/L bicarbonate, 20 mmol/L potassium and 111 mmol/L glucose was used for all patients. The IV infusion was maintained until the rehydration was completed at a rate of 15 to 20 mL/kg/hour. Complete rehydration was successfully achieved in all patients. A total of 89.5 +/- 25.0 mL/kg (mean +/- SD) was needed and the duration of the IV infusion was 5.1 +/- 1.6 hours. Weight gain achieved was 6.5 +/- 1.6%. None of the patients developed hypernatremia following treatment. The initial base deficit, -9.5 +/- 6.6, was reduced to -3.5 +/- 2.9. All of the patients tolerated refeeding immediately after completion of the IV infusion. Our study suggests that this modality of rehydration is well tolerated, safe and effective and enhances the possibility of an early hospital discharge. PMID- 1930718 TI - [Changes in valvular movements of the velopharyngeal sphincter after speech therapy in children with cleft palate. A videonasopharyngoscopic and videofluoroscopic study of multiple incidence]. AB - Thirty-one patients with surgically repaired cleft palate who had velopharyngeal deficiency and compensatory articulatory defects in comparison to hyperrhinophony were studied. All patients were submitted to a videonasopharyngescopic and videofluoroscopic study of multiple incidence before and after speech therapy in order to correct the compensatory articulation. The movement proportions of the pharyngeal velum structures increased significantly after the correction of the compensatory articulation. Even moreso, the size of the pharyngeal velum defect decreased significantly. The results of this study support the postulate which recommends that the articulatory abnormalities associated to hyperrhinophony should be corrected before surgery for pharyngeal velum insufficiency secondary to the closure of the cleft palate. PMID- 1930719 TI - [Neurologic involvement in juvenile rheumatoid arthritis]. AB - The neurologic complication seen in children with juvenile rheumatoid arthritis (JRA) has hardly been studied for which therefore its prevalence is unknown. Some of the clinical manifestations surrounding this event have been studied and have been divided into the following two groups: cervical articular spinal disease and extra-articular manifestations, more commonly seen in adults, the atlas-axoidal subluxation and the neuropathies. A group of 213 children diagnosed as having JRA according to the criteria setforth by the American Association of Rheumatology and followed by the Department of Internal Medicine of the National Institute of Pediatrics, 10 patients were found to have neurologic symptomatology (4.6%). Their arthritis was studied as well as their association with activity data and seropositivity. We found 6 female and 4 male patients with neurologic manifestations; their ages ranged from 7 to 14 years. Six of them were diagnosed with sero-positive polyarticular JRA and the other four with polyarticular sero negative. All patients showed some activity and the appearance of the neurologic complications ranged between two months and seven years. No correlation was found between the beginning of the arthritis and the neurologic symptomatology, their sex or the type of arthritis. Seven of the cases showed peripheral neuropathy. Two cases had atlas-atloid subluxation and another child showed having cervical column inflammation with a rheumatoid pannus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930720 TI - Conditioning and contextual retrieval in hippocampal rats. AB - The role of the hippocampus in associative learning was investigated in 3 experiments with rats as subjects. Hippocampal rats were impaired in the acquisition of conditioned responding both when food was signaled by the insertion of a lever (Experiment 1) and when the presentation of auditory or visual events served as the conditioned stimuli (Experiment 2). Experiment 2 also evaluated the suggestion that deficits in the acquisition of conditioned responding reflect the failure of hippocampal subjects to use contextual cues to retrieve associative information. This experiment showed that hippocampal rats were impaired in learning that a given stimulus was reinforced in Context A but nonreinforced in Context B. Experiment 3 demonstrated that hippocampal rats were unimpaired in learning a simple Pavlovian contextual discrimination. This pattern of results suggests that the hippocampus is involved in a higher order contextual retrieval process. PMID- 1930721 TI - Morphine's effects on differential serial compound conditioning and reflex modification of the rabbit's (Oryctolagus cuniculus) nictitating membrane response. AB - This study sought to determine the effects of morphine (0, 2, and 5 mg/kg) on (a) differential classical conditioning of the rabbit's (Oryctolagus cuniculus) nictitating membrane response (NMR) to the serial compounds A-X-unconditioned stimulus (US) and B-X-US (Experiment 1) and (b) the reflex modification effects of the compounds and their components (Experiment 2). These experiments determined specifically morphine's effects on the distinctiveness and time course of stimulus representations by examining morphine's dose-response effect on (a) differential responding to A and B and their conditional control over responding to X within the compounds and (b) the unconditioned excitatory effects of the compounds and their components as assessed by their ability to modify the amplitude of the unconditioned NMR. The results of these experiments indicate that morphine, in a dose-dependent manner, can operate to profoundly attenuate the distinctiveness and persistence (short-term memory) of stimulus representations. PMID- 1930722 TI - Conditioned incentive properties of a food-paired conditioned stimulus remain intact during dopamine receptor blockade. AB - Hungary rats were exposed to a conditioned stimulus (CS) event (either light onset or offset) before food delivery. After several weeks of contingent CS+/food pairings, animals were pretreated with either 0, 0.5, 0.75, or 1.0 mg/kg pimozide and exposed to the CS+ alone. Both vehicle- and neuroleptic-treated rats showed large elevations in locomotor activity immediately after CS+ presentation, in relation to pre-CS+ activity levels. This elevation in activity was apparently due to the conditioned motivational properties of the stimulus because animals that had previously received unpaired presentations of the CS and food failed to show similar responsiveness to the CS. Although pimozide did not affect responsiveness to the CS+, the neuroleptic did produce an overall suppression of locomotor activity during both pre- and post-CS+ periods. The results suggest that neuroleptic treatment produces a suppression of general activity but leaves the motivational properties of food-paired stimuli intact. PMID- 1930723 TI - Dissociation of brain sites necessary for registration and storage of memory for a one-trial passive avoidance task in the chick. AB - Although memory formation occurs in a sequence of pharmacologically dissociable stages, many models assume that this sequence is located within a single neuronal ensemble. Three forebrain areas in the young chick-the intermediate medial hyperstriatum ventrale (IMHV), the lobus parolfactorius (LPO), and the paleostriatum augmentatum--have been identified as important structures in mediating learning and memory processes. It has been shown that pretraining lesions placed to the left IMHV produce amnesia for a 1-trial passive avoidance task. Posttraining lesions in the IMHV are not amnestic. The present study demonstrated that bilateral lesions to the LPO are amnestic but only if made subsequent to rather than before training. These results suggest that long-term storage of the memory is dependent on the LPO. Further experiments determined that in the absence of the LPO at training, the right IMHV can act a long-term memory storage site. In the absence of the right IMHV at training, other, as yet undetermined, areas can take up this role. PMID- 1930724 TI - Corpus callosum: interactive effects of infantile handling and testosterone in the rat. AB - Previous research found that the corpus callosum of male rats is larger than that of females; handling rats in infancy enhances this sex difference; and female rat pups, when handled in infancy and given 1 injection of testosterone propionate (TP) on Day 4 of life, will have callosa as large as those of males. In 2 experiments, male pups were castrated on Day 1 or received sham surgery; female pups were injected with TP on Day 4 or received an oil injection. Litters were handled or nonhandled. The previous finding that females, when handled and given TP in infancy, have a larger callosum was confirmed; however, a TP effect when administered to nonhandled females was not found. Because handling is known to cause a corticosterone release, these findings were interpreted as evidence of a developmental interaction between adrenal and gonadal hormones at the cortical level. PMID- 1930725 TI - Response-related deficits following unilateral lesions of the medial agranular cortex of the rat. AB - Rats with lesions of the medial agranular frontal cortex (AGm) were tested for sensorimotor function. Spatial response bias and reaction time to lateralized visual targets were recorded in an automated test of visual reaction time. The same rats were also tested for somatosensory capacity and on a skilled reaching task. In all tasks, there was an ipsilateral response bias but no evidence of sensory neglect. In the visual reaction time task, initiation time was lengthened bilaterally. These deficits may parallel the effects on motor function after unilateral frontal cortical lesioning in primates. The results support the hypothesis that rat AGm contains a homologue of primate secondary motor cortex. PMID- 1930726 TI - Mesotelencephalic dopamine system and reproductive behavior in the female rat: effects of ventral tegmental 6-hydroxydopamine lesions on maternal and sexual responsiveness. AB - The effects of lesions to the mesolimbic dopamine system on maternal and sexual behaviors in the female rat was assessed. Rat dams that were given ventral tegmental area microinfusions of 6-hydroxydopamine (6-OHDA) during lactation showed a persistent deficit in pup retrieval but were not impaired with respect to nursing, nest building, or maternal aggression. In addition, 6-OHDA-lesioned females failed to respond to amphetamine by showing locomotor hyperactivity. Administration of the dopamine blocker raclopride to neurologically intact dams also inhibited pup retrieval but had no effect on nursing. Females given 6-OHDA during pregnancy appeared completely unresponsive to pups, whereas no maternal deficits were seen in females that received 6-OHDA 8 weeks before parturition. Proceptive (hopping and darting) and receptive (lordosis) components of sexual behavior, assessed after ovariectomy and exogenous steroid hormone treatment, were not affected by mesolimbic 6-OHDA lesions. PMID- 1930728 TI - Reversal of the sodium chloride aversion of Fischer 344 rats by chorda tympani nerve transection. AB - Fischer 344 (F344) rats are atypical in their lack of preference for any concentration of NaCl solution over water. It was hypothesized that abnormal signals mediated by the chorda tympani nerve (CT) could be causally involved in NaCl avoidance by F344 rats. This study assessed whether CT transection would normalize the salt preference of F344 rats. Preference for NaCl solutions (0.6%, 0.8%, and 1.0%) versus water was assessed using two-bottle preference tests. At all concentrations tested, CT-transected animals preferred NaCl solutions to water. This preference differed dramatically from the avoidance of these solutions by controls. These findings are striking, particularly because CT transections have generally failed to significantly affect NaCl preference in other rat strains. The results are consistent with the hypothesis that in F344 rats the avoidance of the taste of NaCl stems from input mediated by the CT. PMID- 1930727 TI - Associative processes in adaptation to repeated cold exposure in rats. AB - Learning processes have been implicated in drug tolerance, but the role of associative mechanisms in adaptation to stressors has not previously been determined. Rats that received daily brief cold exposures demonstrated adaptation to the cold as measured by an attenuation of hypothermia. Tolerance to the cold was disrupted by changing the context in which the subject experienced the cold. These findings provide evidence of associative processes in adaptation to cold exposure and illustrate that these processes are not limited to drug tolerance. PMID- 1930729 TI - Porcine pancreatic cationic pro-elastase. Studies on the activation, turnover and interaction with plasma proteinase inhibitors. AB - Porcine pancreatic cationic pro-elastase was partly purified from pancreatic juice. The pro-enzyme binds slowly to alpha-macroglobulin and alpha 1-proteinase inhibitor. After 24 h incubation with plasma at room temperature more than 50% of the pro-elastase was still recovered in the form of free pro-enzyme. The pro enzyme was activated by trypsin at neutral pH and by cathepsin B at pH 3.8. In the pig the half-life of i.v. administered pro-enzyme was about 30 min. After injection into the pancreatic duct radioactively labelled pro-elastase appeared in plasma within 30 min, and in peritoneal fluid after about 1 h. PMID- 1930731 TI - Transient expression of wild type and mutant human apolipoprotein AI in COS cells. AB - A human apolipoprotein AI (apo AI) minigene and two mutants were cloned into the vector pUHD10-1 for expression studies in COS cells under the control of the strong CMV (cytomegalovirus) enhancer and the own apo AI promoter. In the mutated apo AI minigene (mutant M1) the positions of the triplets of Gln(-2)-Gln-1 at the C-terminus of the prosequence were exchanged against Gln(-8)-Ala-7, the recognition site of the signal peptidase of the wild type human apo AI. The prosequence has been deleted in mutant M2 and the presequence linked directly to the N-terminus of the mature apo AI form. We report here on expression studies in COS cells, a cell line, which does not express apo AI. They were transfected by electroporation with pUHD10-1 constructs, which contain a) the wild type apo AI minigene and b) the two mutant apo AI minigenes with mutations described above. The following results were obtained: a) the wild type and mutant apo AI constructs were efficiently transcribed and translated in COS cells, b) the expression of the wild type preproapo AI minigene in COS cells led to the secretion of proapo AI (29 kDa), that of the mutant (M2) gene, devoid of the prosequence of mature apo AI (28.4 kDa), whereas the product of mutant gene M1 (31 kDa) with the recognition site of the signal peptides transposed to the C terminus of the prosequence remained uncleaved within the COS cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930730 TI - Primary structure of hemoglobin from monitor lizard (Varanus exanthematicus albigularis--Squamata). AB - The primary structure of the major hemoglobin component from the Monitor Lizard Varanus exanthematicus albigularis is presented. The polypeptide subunits were separated by reversed-phase high-performance liquid chromatography on Nucleosil C 4 column. The amino-acid sequence was established by automatic Edman degradation of the native polypeptide and its tryptic and hydrolytic cleavage products in a spinning cup sequencer. The structural data are discussed with reference to other reptiles. PMID- 1930732 TI - Semisynthetic des-(B27-B30)-insulins with modified B26-tyrosine. AB - Semisynthetic des-(B27-B30)-insulins containing modified B26-tyrosine residues were prepared to refine the understanding of the importance of position B26 with regard to biological and structural properties of the hormone. The following shortened insulin analogues were synthesized by trypsin-catalysed peptide-bond formation between the C-terminal amino acid ArgB22 of des-(B23-B30)-insulin and synthetic tetrapeptides as amino components: des-(B27-B30)-insulin, des-(B27-B30) insulin-B26-methyl ester, -B26-carboxamide with varying C-terminal hydrophobicity of the B-chain, and [Tyr(NH2)B26]-, [Tyr(NO2)B26]-, [Tyr(I2)B26]-, [D-TyrB26]des (B27-B30)-insulin-B26-carboxamide containing non-proteinogenic amino acids in position B26. Starting from insulin and an excess of synthetic Gly-Phe-Phe-Tyr OMe as nucleophile, des-(B27-B30)-insulin-B26-methyl ester--the formal transpeptidation product at ArgB22--was formed in one step. Biological in vitro properties (binding to cultured human IM-9 lymphocytes, relative lipogenic potency in isolated rat adipocytes) of all semisynthetic analogues are reported, ranging from slightly decreased to two-fold receptor affinity and nearly three fold biopotency relative to insulin. If the C-terminal tetrapeptide B27-B30 is removed, full relative insulin activity is still preserved, while the shortening results in the loss of ability to associate in solution. Only after carboxamidation or methyl esterification of TyrB26 the self-association typical of native insulin can be observed, and the CD-spectral effects in the near UV spectrum related to association and hexamerization of the native hormone are qualitatively reestablished. The results of this investigation underline the importance of position B26 to the modulation of hormonal properties and solution structure of the shortened insulins. PMID- 1930733 TI - The amino-acid sequence of three proteins of photosystem I of the cyanobacterium Fremyella diplosiphon (Calothrix sp PCC 7601). AB - Three proteins containing 138 amino acids (psaD protein), 80 amino acids (psaC protein) and 66 amino acids (psaE protein) of the photosystem I (PS I) complex of the cyanobacterium Fremyella diplosiphon (Calothrix sp PCC 7601) were isolated and sequenced. Comparison with previously known sequences showed a close relationship to homologous proteins of Nostoc, another filamentous cyanobacterium. PMID- 1930734 TI - Restorative materials. AB - Veterinarians have a wide variety of types and brands of dental restorative materials available. An appreciation for the types of restorative materials is necessary for their successful placement. The rationale for use, types and technique for placement of bonding agents, composite resins, amalgams, and light cure restoratives are presented. PMID- 1930735 TI - Split palatal U-flap: a new technique for repair of caudal hard palate defects. AB - Oronasal fistulas located in the central portion of the hard palate can be surgically repaired using a transposition flap of hard palate mucoperiosteum from tissue adjacent to the defect. The purpose of this report is to describe a new technique, the split palatal U-flap, for the surgical repair of large caudal hard palate defects in the dog and cat. A description of this new technique and case reports of a dog and a cat in which this technique was utilized to repair caudal hard palate defects are included. PMID- 1930736 TI - Aerobes in periodontal disease in the dog: a review. AB - Periodontal disease has been shown to be caused by bacteria. Periodontal inflammation results as the plaque bacteria change from a predominantly non motile, Gram-positive, aerobic coccoid microbiotal flora to a more motile, Gram negative, anaerobic, rod-shaped flora. A review of the literature related to aerobic flora is included. The important effects of aerobic flora as well as their importance in contributing to periodontal disease development is reported. PMID- 1930737 TI - Recent developments in computer-assisted diagnosis of putative adverse drug reactions. PMID- 1930738 TI - Risk-benefit assessment of antiarrhythmic drugs. An epidemiological perspective. PMID- 1930739 TI - Hyperbaric oxygen treatment for carbon tetrachloride poisoning. AB - Carbon tetrachloride (CCl4) undergoes hepatic reductive metabolism to trichloromethyl (.CCl3) and peroxytrichloromethyl (CCl3OO.) free radicals, toxic intermediates which may initiate hepatocellular damage. Recent investigations have demonstrated a potential role for hyperoxia and hyperbaric oxygen as therapeutic interventions for CCl4 poisoning. Elevated oxygen concentrations in vitro and in vivo reduce lipid peroxidation and hepatotoxicity. In vivo studies of hyperbaric oxygen following administration of CCl4 in a rat model have shown improved survival and decreased hepatotoxicity. Case reports of human poisoning, with potentially lethal ingested doses of CCl4, also suggest a potential role for treatment with hyperbaric oxygen. Hyperoxia may act by altering the metabolism of CCl4. These studies and case reports support the recommendation that 100% normobaric and hyperbaric oxygen should be treatment considerations for CCl4 poisoning. PMID- 1930741 TI - Systemic lupus erythematosus (SLE)-like syndromes associated with carbamazepine therapy. AB - Records of 80 cases of systemic lupus erythematosus (SLE)-like syndromes associated with use of carbamazepine entered in the single case files of Central Drug Monitoring, Ciba-Geigy, Basel, were reviewed. Included in these were 11 cases reported in the literature. These were assessed in light of the current concepts of both idiopathic and drug-induced forms of SLE. Even allowing for under-reporting of adverse drug reactions, the number of such cases is far below the prevalence rates for SLE. This adverse drug reaction remains allocated to the category 'isolated cases' i.e. frequency is less than 0.001% of the cases treated. Antinuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) tests were not helpful in differentiating between idiopathic and drug-induced SLE. IgG antihistone antibodies in the absence of high titres of dsDNA antibodies is the only reliable test. Symptoms of SLE-like syndromes which manifest after carbamazepine therapy usually subside after discontinuation of the drug. Persistence of symptoms support the diagnosis of idiopathic SLE. PMID- 1930740 TI - The clinical significance of antibiotic-associated pseudomembranous colitis in the 1990s. AB - Antibiotic-associated pseudomembranous colitis is an uncommon but potentially serious adverse reaction, resulting in acute diarrhoea and characterised by colonic pseudomembranes. A direct relationship between the disease, recent antibiotic therapy and proliferation of Clostridium difficile in the colonic lumen was established in the late 1970s. It is thought that antibiotic therapy may alter the enteric flora, enabling C. difficile to proliferate and produce toxins with cytopathic (toxin B or cytotoxin) and hypersecretory (toxin A or enterotoxin) effects on the mucosa. Apart from clindamycin, the first antibiotic recognised to be clearly associated with pseudomembranous colitis, the antimicrobial agents most commonly responsible are cephalosporins and ampicillin (or amoxicillin). However, virtually all antibiotics except parenterally administered aminoglycosides can cause the disease. Vancomycin and metronidazole, 2 drugs used to treat antibiotic-associated pseudomembranous colitis, have also been reported to be responsible for the complication when used parenterally. Pseudomembranous colitis may develop after perioperative prophylactic antibiotic therapy with cephalosporins. Antibiotic-associated pseudomembranous colitis is most frequent in elderly and debilitated patients and in intensive care units. Nosocomial acquisition of C. difficile has been documented. Therefore it has been recommended that enteric isolation precautions should be taken with patients with this disease. The clinical symptoms include watery diarrhoea, abdominal cramping, and frequently fever, leucocytosis and hypoalbuminaemia. Toxic megacolon and acute peritonitis secondary to perforation of the colon are the most serious complications. The pseudomembranes are usually seen during endoscopic procedures, sigmoidoscopy or, if possible, colonoscopy; the most useful microbiological tests for confirmation of the diagnosis include cycloserine cefoxitin fructose agar (CCFA) stool cultures and stool toxin assays on tissues or by immunological techniques. However, cultures and toxin tests may be positive in patients without pseudomembranous colitis or C. difficile-associated diarrhoea. Mild cases may respond to discontinuation of the drug responsible, but therapy with an anticlostridial antibiotic is often necessary: a 10-day course of oral vancomycin, metronidazole or bacitracin should be given. Relapses are seen in 5 to 50% of patients treated. Antibiotic treatment should avoid sporulation leading to other relapses. 'Biotherapy' (lactobacilli, Saccharomyces) has also been proposed. PMID- 1930743 TI - Risk-benefit assessment of tocolytic drugs. AB - beta 2-Mimetics are the principal agents used for myometrial relaxation. As all the available drugs also have beta 1-stimulant effects, the various side effects (cardiovascular, pulmonary and metabolic) require a critical consideration of the clinical indications, thorough supervision and combined therapeutic concepts. With regard to clinical indications, 'prophylactic tocolysis' frequently turns out to be unnecessary, as does the treatment of physiological uterine contractions during pregnacy which have no effect on the cervix. The benefit of tocolysis must be seen not so much in a reduction of preterm labour but in enabling the obstetrician and neonatologist to optimise the handling of the premature baby, e.g. by allowing lung maturation or by enabling the patient to reach a centre for perinatal medicine before the birth. Labour-dependent fetal distress situations during birth at term can also be managed successfully. Supervision involves thorough control of both mother (especially of cardiovascular and metabolic parameters, electrolyte and water balance) and fetus (cardiotocography, fetometry) in order to decide individually when possible benefits are outweighed by maternal or fetal risks. Combination of beta 2-mimetic treatment with magnesium therapy reduces the beta-mimetic dosage required, has a cardioprotective action, and reduces the development of drug tolerance and the risk of lung oedema. This combination, therefore, should become routine in tocolytic therapy. If further protection against cardiovascular and risk of lung oedema is required, administration of beta 1-blockers is advisable. PMID- 1930742 TI - Angiotensin converting enzyme (ACE) inhibitors and renal function. A review of the current status. AB - Angiotensin converting enzyme (ACE) inhibitors are well established in the treatment of hypertension and cardiac failure. Experimental studies in rats have suggested that these agents may protect renal function in chronic nephropathy by a mechanism other than simply lowering the systemic blood pressure. In human studies of incipient diabetic nephropathy, worsening of microalbuminuria was prevented during 3 years of ACE inhibition. ACE inhibitors reduce arterial blood pressure in chronic nephropathy, and may cause a fall in glomerular filtration rate. In diabetic nephropathy, proteinuria was reduced by 2 months' treatment with enalapril to less than half of the values obtained in a control group treated with metoprolol. Nonrandomised trials have suggested that ACE inhibitors may slow the deterioration of renal function, but no comparisons with other antihypertensive agents in prospective studies have been published to date. In chronic renal failure, ACE inhibitors may worsen anaemia and hyperkalaemia. Renovascular hypertension can be treated with ACE inhibitors, but the treatment may lead to a compromised renal function. The dosage of these drugs should be reduced in renal failure and therapy should be started cautiously in this setting, with close monitoring of blood pressure, renal function and plasma potassium. PMID- 1930744 TI - Statistical methods in pharmacoepidemiology. Principles in managing error. AB - To successfully appraise the significance of epidemiological data on drug risk and safety requires a good understanding of the errors involved in the design and analysis of pharmacoepidemiological studies. A proper comprehension of the repercussions of these errors and of the strengths and limitations of the tools used to measure their magnitude are essential to sound decision making by the regulatory, industry or clinical consumers of these data. In this paper, we examine the role of statistics in managing the quantifiable errors present in pharmacoepidemiological data analysis and interpretation. Some epidemiological principles on the measurement of risk are first introduced. The influences of controllable systematic error and random error on our assessment of epidemiological data are then presented, along with the prevailing statistical principles and measures necessary to control these errors. To illustrate the various issues addressed, published data on the risks of NSAIDs, focusing particularly on upper gastrointestinal bleeding (UGIB), the risks of replacement estrogens for endometrial cancer and the safety of allopurinol for cataracts are used as examples throughout. PMID- 1930745 TI - Sister chromatid exchange in patients treated with nonsteroidal anti-inflammatory drugs. PMID- 1930746 TI - The serotoninergic system of the brain of the viper, Vipera aspis. An immunohistochemical study. AB - Serotoninergic cell bodies and fibers in the brain of the viper, Vipera aspis, were visualized by immunohistochemistry. Immunoreactive cell bodies were observed in the diencephalic hypothalamic periventricular organ and in the dorsal wall of the infundibular recess, in the nuclei raphe superior and inferior of the midbrain and hindbrain, and to a lesser extent in the nuclei reticularis superior, reticularis inferior and reticularis lateralis. In contrast to other reptilian species, serotoninergic cells were also observed in the central gray matter of the midbrain in the neighbourhood of the nucleus of the trochlear nerve. Immunoreactive fibers are widely distributed throughout the brain of the viper. In the olfactory bulb, fibers were observed in the internal plexiform layer and mitral cell layer. The cerebral cortex contains the highest density of fibers in the dorsal region. The distribution of immunoreactive fibers in the dorsal ventricular ridge is extremely heterogeneous, and five subcomponents of this structure can be distinguished. The majority of diencephalic and mesencephalic structures that contain immunoreactive fibers are also primary visual centres: the nuclei geniculatus lateralis pars dorsalis, the n. posterodorsalis and n. opticus tegmenti, and the optic tectum. Serotoninergic fibers in the nuclei of the oculomotor and motor cranial nerves (III, IV, V, VII, X) are disposed in a tightly woven basket around the non-immunoreactive cell bodies of the motoneurons. These findings, together with the available literature, suggest that the serotoninergic system in snakes is comparable to that in lizards, with a massive ascending projection of fibers from the n. raphe superior to mesencephalic and prosencephalic structures, and a descending projection from the n. raphe inferior to the spinal cord. PMID- 1930747 TI - Complementary immunohistochemical distribution of the neurofilament triplet and novel intermediate filament proteins in the autonomic and sensory nervous system of the guinea-pig. AB - We have previously established that immunoreactivity for the triplet of polypeptides that comprise the class IV intermediate filament proteins (NFP triplet) is localized in specific subpopulations of neurons in guinea-pig sensory and autonomic ganglia. Antibodies to novel neurofilament proteins, including a polyclonal antibody to a 57 kDa neuronal intermediate filament polypeptide (NIF57kD) and a monoclonal antibody (CH1) to a 150 kDa intermediate filament, or associated, protein were used in combination with antibodies to the NFP-triplet for double-labelling immunohistochemistry. The results show that different subpopulations of neurons in the guinea-pig dorsal root ganglia, coeliac ganglion and enteric ganglia can be distinguished by their complementary immunoreactivity for these proteins. In dorsal root ganglia, larger neurons are intensely immunoreactive for the NFP-triplet while immunoreactivity with CH1 and NIF57kD antibodies is restricted to the small to medium-sized neurons. In the coeliac ganglion, two regionally defined subpopulations of neurons can be distinguished by their immunoreactivity for either the NFP-triplet or NIF57kD, whereas CH1 labels all neurons with equal intensity. Three classes of morphologically distinct myenteric neuron subpopulations are also distinguished by their immunoreactivity for either the NFP-triplet, NIF57kD or CH1 antibodies. Two classes of submucous neurons are labelled both with CH1 and NIF57kD antibodies but show faint or no immunoreactivity for the NFP-triplet. It is concluded that intermediate filament protein immunoreactivity marks different subpopulations of neurons, which suggests that these proteins may have specific roles in neuronal function. PMID- 1930748 TI - Acetylcholinesterase and NADH-diaphorase chemoarchitectonic subdivisions in the rabbit medial geniculate body. AB - The distribution of acetylcholinesterase and NADH-diaphorase activities was studied histochemically in the rabbit medial geniculate body, yielding new data useful for the definition of the common structural pattern of this thalamic complex in mammals. Four chemoarchitectonic subdivisions could be detected in transversal, horizontal and sagittal sections that corresponded to the previously described ventral, dorsal and internal nuclei, and to a fourth subdivision, defined as the mediorostral nucleus of the medial geniculate complex in the rabbit. The topography and cellular typology of the mediorostral nucleus suggest its homology with the so-called magnocellular nucleus of other mammals, an identity that was previously assigned to the internal nucleus. The relative position of the rabbit internal and dorsal nuclei and comparative connectional data are combined to suggest their correspondence with the anterodorsal and posterodorsal subnuclei, respectively, of the cat and the monkey. Global functional interpretations of these nuclei as sites of visuoacoustic and somatoacoustic polymodal integration support the notion of a shell region of the medial geniculate, surrounding the principal cochleotopic ventral nucleus and interconnected to the cortical acoustic belt around the primary auditory area. Acetylcholinesterase and NADH-diaphorase chemoarchitectony may be useful for the detection of similar partitions in species where cytoarchitectonic differentiation of the medial geniculate is less clear. PMID- 1930750 TI - Qualitative age differences in memory for text: a life-span developmental perspective. AB - Qualitative differences in memory for text among 4 age groups (mean ages = 14.14, 17.55, 48.35, and 67.12 years) were examined in this study. Participants produced written recall and summary responses after presentation of a story and an essay. The response protocols were scored for their reproductive, elaborative, and metaphoric content. Age-group differences were observed in the quality of the responses. In general, the adolescent recall and summary responses were reproductive and text based, whereas the adult responses were more reconstructive and interpretive. Age-group differences were especially apparent in the story condition: The adolescents recalled and summarized the story's propositional content, whereas many of the adults recalled and summarized the story's psychological and metaphoric meanings as well. Individual difference variables accounted for much of the age-related variability in the essay but not in the story responses. PMID- 1930749 TI - Immunohistochemical mapping of neurophysins and calcitonin gene-related peptide in the human brainstem and cervical spinal cord. AB - Our study investigates the distribution of neurophysins (Nph), proteins that are part of the precursors for vasopressin and oxytocin, and calcitonin gene-related peptide (CGRP) in the human brainstem by immunohistochemistry. Both peptides were found in discrete regions of the human hindbrain. Nph could be demonstrated exclusively in fibers and punctate perineural varicosities that were travelling within the mesencephalic central gray, substantia nigra, as well as locus coeruleus, medial longitudinal fascicle, raphe, nucleus of the solitary tract, lateral reticular nucleus and area postrema. A few varicosities were seen in the substantia gelatinosa of the spinal trigeminal tract and its continuation into the dorsal horn of the cervical spinal cord. In contrast to these observations. CGRP-immunoreactive fibers were found to be densest in the spinal tract of the trigeminal nerve and the dorsal horn of the spinal cord. In addition, fibers and varicosities could be demonstrated in numerous distinct brain regions, such as locus coeruleus and subcoeruleus, solitary tract, cuneate nucleus, raphe and periaqueductal gray. CGRP-immunoreactivity was also present in perikarya in the ventral horn of the spinal cord, as well as motor nuclei of cranial nerves, i.e., hypoglossal nucleus, ambiguous nucleus. Our results suggest that Nph immunoreactivity in the human brainstem may be present predominantly within long fiber projections from hypothalamic neurosecretory nuclei, in analogy to data obtained from rodents, whereas CGRP may play a role in the branchiomotor system as well as in intrinsic or extrinsic projections involved in autonomic regulation and integration of sensory information. PMID- 1930751 TI - Instantiation of general terms in young and older adults. AB - Instantiation of general terms in discourse requires inference from general world knowledge and use of linguistic context to particularize meaning. According to the semantic deficit hypothesis, older adults should be less likely than young adults to generate or to store such inferences. In Experiments 1 and 2 an indirect measure, relatedness judgment, was used to assess immediate comprehension and memory for inferences. In Experiment 3 a direct measure, cued recall, was used to tap memory for inferences. No age differences in immediate or delayed memory were observed in Experiments 1 or 2. In Experiment 3 older adults recalled fewer sentences, but there was no evidence for a specific decrement in storage of inferential material. Older adults are not impaired in ability to draw inferences based on general world knowledge, nor are they more likely than young adults to encode linguistic information in a general, stereotypic fashion. PMID- 1930752 TI - Protective functions of health and self-esteem against depression in older adults facing illness or bereavement. AB - Four functions were examined by which health and self-esteem could ward off depression over time in older adults. Adults (N = 1,074)--55 years and older- were interviewed 5 times at 6-month intervals. Demographic and prevent depression controls were included. Neither health nor self-esteem served as an interactive buffer. Both had direct negative effects on depression, independent of events, over 2 years. Neither illnesses nor bereavements had direct effects on depression; both had indirect effects through other events; illness also had indirect effects by weakening health. Health had stronger preventive effect on illnesses but was more vulnerable to undesirable events than was self-esteem. There was little support for the specificity hypothesis that a close match between event and resource would increase resource effects. PMID- 1930753 TI - Personality and aging: a study of the MMPI-2 among older men. AB - We examined whether separate norms for older men are necessary for the revised Minnesota Multiphasic Personality Inventory (MMPI-2). Scores from 1,459 men in the Normative Aging Study (NAS) (age: M = 61.27, SD = 8.37) were contrasted with those from 1,138 men from the MMPI Restandardization Study (age: M = 41.71, SD = 15.32). Results showed that scores on the MMPI-2 validity, clinical, and content scales for the NAS men were highly similar to those from the MMPI-2 Restandardization sample. There were also few differences between the two groups at the item level. Within-sample analyses revealed some differences between age groups. However, the magnitudes of these differences were small and may represent the single or combined effects of cohort factors and age-related changes in physical health status rather than age-related changes in psychopathology per se. We concluded that special, age-related norms for the MMPI-2 are not needed for older men. PMID- 1930754 TI - Relationship between rigidity-flexibility and cognitive abilities in adulthood. AB - The interrelationship of measures of rigidity-flexibility and of psychometric intelligence is examined. The latent factors of Attitudinal Flexibility, Motor Cognitive Flexibility, and Psychomotor Speed are derived from the Test of Behavioral Rigidity, and factors of Inductive Reasoning, Spatial Orientation, Verbal Ability, Numeric Ability, Verbal Memory, and Perceptual Speed are derived from the Thurstone Primary Mental Abilities Test and the Educational Testing Service Kit of Factor-Referenced Tests. The data base in this study comes from the fifth wave of the Seattle Longitudinal Study (N = 1,628; age range, 22-95 years). The Rigidity-Flexibility factors were found to be independent of the cognitive domain. Also, longitudinal stability of the factor structure of the rigidity-flexibility domain was confirmed for 837 participants tested in both 1977 and 1984. PMID- 1930755 TI - Involuntary retirement, Type A behavior, and current functioning in elderly men: 27-year follow-up of the Western Collaborative Group Study. AB - Data from 1,103 community-dwelling male participants (mean age = 71.7 years) in a 27-year cardiovascular disease follow-up were used to examine health and mental health sequelae in voluntarily and involuntarily retired Type A individuals. After controlling for age, education, and occupation, Type A subjects, determined both at intake (1960-1961) and at follow-up (1986-1987), reported significantly more frequently that retirement was involuntary. Regardless of Type A status, those reporting involuntary retirement also tended to have poorer adjustment to retirement, more illness, poorer physical status, and more depressive symptomatology. Minimal evidence was obtained on a broad array of indicators for psychological, physical, cognitive, and health status that Type As who retired involuntarily fared worse in retirement than those who retired voluntarily. PMID- 1930756 TI - Predictors of burden in spouse caregivers of individuals with Alzheimer's disease. AB - This study used the following model of distress: Distress = [Exposure to Stress + Vulnerability]/[Psychological and Social Resources]. The constructs in the model were operationalized as (a) distress in response to caregiver experiences (burden); (b) exposure to stress (care recipient functional impairment in activities of daily living [ADLs]); (c) vulnerability (caregiver health problems, anger, and anxiety); and (d) resources (coping, outlook on life, and social supports). Long-term burden (15-18 months after entry) was predicted by several baseline variables: burden, care recipient ADLs, vulnerability and resource variables, and specific interactions of burden, ADLs, vulnerability, and resource variables. The interactions showed that caregivers with high vulnerability and low resources had higher burden scores than caregivers with other combinations of these variables. PMID- 1930758 TI - How general is general slowing? Evidence from the lexical domain. AB - Three analyses are reported that are based on data from 19 studies using lexical tasks and a reduced version of the Hale, Myerson, and Wagstaff (1987) nonlexical data set. The results of Analysis 1 revealed that a linear function with a slope of approximately 1.5 described the relationship between the lexical decision latencies of older (65-75 years) and younger (19-29 years) adults. The results of Analysis 2, based on response latencies from 6 lexical tasks other than lexical decision, revealed a virtually identical linear relationship. In Analysis 3, it was found that performance on nonlexical tasks spanning the same range of task difficulty was described by a significantly steeper regression line with a slope of approximately 2.0. These findings suggest that although general cognitive slowing is observed in both domains, the degree of slowing is significantly greater in the nonlexical domain than in the lexical domain. In addition, these analyses demonstrate how the meta-analytic approach may be used to determine the limits to the external validity of experimental findings. PMID- 1930757 TI - Visual/cognitive correlates of vehicle accidents in older drivers. AB - Older drivers have more accidents per miles driven than any other age group and tend to have significant impairments in their visual function, which could interfere with driving. Previous research has largely failed to document a link between vision and driving in the elderly. We have taken a comprehensive approach by examining how accident frequency in older drivers relates to the visual/cognitive system at a number of levels: ophthalmological disease, visual function, visual attention, and cognitive function. The best predictor of accident frequency as recorded by the state was a model incorporating measures of early visual attention and mental status, which together accounted for 20% of the variance, a much stronger model than in earlier studies. Those older drivers with a visual attentional disorder or with poor scores on a mental status test had 3-4 times more accidents (of any type) and 15 times more intersection accidents than those without these problems. PMID- 1930759 TI - Age and experience effects on the interpretation of orthographic drawings of three-dimensional objects. AB - Adults of different ages and experience levels attempted to recognize wire-frame drawings of 3-dimensional objects originally displayed in orthographic views. Although only slight age relations were evident on a measure of decision accuracy in the criterion task, increased age was associated with poorer performance on several tasks hypothesized to assess component processes. Furthermore, there was no significant alteration in any of the performance measures by statistically controlling for amount of relevant experience, and there was no evidence that people of different ages, or different levels of experience, relied on different abilities to perform the criterion task. These results seem to imply that experience neither mediates nor moderates age-related influences on certain measures of relatively basic cognitive processes. PMID- 1930760 TI - The effects of late-life spousal bereavement over a 30-month interval. AB - Self-report measures of grief, depression, and general psychopathology were studied in widows and widowers over a 2.5-year period following death of their partner. A comparison sample of men and women was also followed for the same period. Differences in severity of depression and psychopathology previously reported at 2 months postloss (Gallagher, Breckenridge, Thompson, & Peterson, 1983) diminished to nonsignificant levels at 12 and 30 months. However, significant differences between bereaved and comparison subjects on measures of grief were still apparent 30 months after spousal loss. A main effect of gender for depression and psychopathology (but not for grief) was found at 2 and 12 months: Women reported more distress than men regardless of bereavement status. Results indicate that the experience of grief persists for at least 30 months in both older men and women who have lost their spouse. PMID- 1930761 TI - Evaluative perceptions of patronizing speech addressed to elders. AB - Within a speech accommodation framework, speech modifications based on stereotyped expectations of elderly persons (such as patronizing speech) are hypothesized to convey less respect. Adult volunteers (N = 186) read scripts of a conversation between a nurse caregiver, using either patronizing speech or a more neutral variant, and a 76-year-old nursing home resident, depicted either as alert or forgetful. Respondents viewed the nurse in the patronizing condition as significantly less respectful and less nurturant and the recipient as more frustrated. The patronizing nurse was also rated as significantly less competent and benevolent than her counterpart in the neutral condition. The ecological validity of the contrasts between scripts was confirmed by inferences that patronizing speech was more shrill, louder, and produced with more exaggerated intonation. PMID- 1930762 TI - Age differences in the maintenance and restructuring of movement preparation. AB - In 2 experiments, elderly and young subjects performed simple reaction time, choice reaction time, and movement plan restructuring tasks, using a stimulus precuing paradigm. In Experiment 1, the precue display (200 ms) and preparation interval (250, 500, 750, or 1,000 ms) were experimentally determined. In Experiment 2, the precue display interval was subject determined. For the restructuring task, the precue specified the response on 75% of the trials, enabling movement plan preparation with respect to movement parameters of arm and direction. On remaining trials, the precue incorrectly specified the response, requiring movement plan restructuring. Elderly, but not young, subjects restructured a movement plan for direction more quickly than for arm or for both parameters. These findings indicate that elderly individuals have poorer movement plan maintenance for direction than for arm and thus exhibit functional change in movement preparation processes relative to young individuals. PMID- 1930763 TI - Anxiety and depressive disorders in adult children caring for demented parents. AB - Current and lifetime rates of disorders outlined in the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev., DSM-III-R) were compared in 78 adult children caring for a parent with a progressive dementia and 78 control subjects. The frequencies of depressive and anxiety disorders did not differ between groups in the years prior to caregiving, and there were no differences between groups in first-degree relatives' incidence of psychiatric disorder. During the years they had been providing care, 34% of caregivers met DSM-III-R criteria: 24% for a depressive disorder and 10% for an anxiety disorder. In contrast, 8% of the matched controls met criteria during the same time period for depressive or anxiety disorders. Results support the chronic strains of caregiving being linked to the onset of both depressive and anxiety disorders in adult children caring for a demented parent. PMID- 1930764 TI - Cognitive addition: strategy choice and speed-of-processing differences in young and elderly adults. AB - Sixty young and 60 elderly adults completed a pencil-and-paper addition test and solved 40 computer-presented simple addition problems. Strategies and problem solution times were recorded on a trial-by-trial basis and were classified in accordance with the distributions of associations model of strategy choices. The elderly group showed a performance advantage on the ability measure and for the developmental maturity of the mix of problem-solving strategies, but the young group showed an advantage for overall solution times. A componential analysis of the overall solution times for memory retrieval trials, however, showed no reliable age difference for rate of retrieving addition facts from long-term memory but did suggest that the elderly adults might have been slower than the younger adults for rate of encoding digits and verbally producing an answer. Overall results are interpreted within the context of the strategy choice model. PMID- 1930765 TI - Stories as a mnemonic aid for older learners. AB - The effectiveness of a story mnemonic for free-recall learning was assessed in 71 community-dwelling elderly adults. Participants received 1 of 3 memory-training programs: (a) narrative story, (b) method of loci, or (c) placebo training. The stimuli consisted of 26 nouns chosen for being highly imagible and concrete. Recall was examined immediately following study of the words, after 1 hr, and after 3 days. At each testing interval, both mnemonic condition groups outperformed the placebo group. The results suggest that a story mnemonic can enhance word retention on a free-recall task. PMID- 1930766 TI - The effect of exercise on depressive symptoms in the moderately depressed elderly. AB - Thirty community-dwelling, moderately depressed elderly were randomly assigned to 1 of 3 interventions: experimenter-accompanied exercise in the form of walking, a social contact control condition, and a wait-list control. Exercise and social contact both resulted in significant reductions in both the total and the psychological subscale of the Beck Depression Inventory (BDI). The exercise condition, however, unlike the control conditions, resulted in decreased somatic symptoms of the BDI. These results indicate that, at least in the short term, exercise has a broader effect compared with control conditions in reducing depressive symptoms in the moderately depressed elderly. PMID- 1930767 TI - The generalizability of training gains in dementia: effects of an imagery-based mnemonic on face-name retention duration. AB - The generalizability of the results from a case study on the effects of an imagery mnemonic on face-name recall in dementia was examined (Hill, Evankovich, Sheikh, & Yesavage, 1987). Seven patients with Alzheimer's disease (AD) and 1 patient with multi-infarct dementia (MID) were trained by using the method devised by Hill et al. Application of the mnemonic increased the time during which face-name associations could be held in memory for 1 AD patient, and this improvement was maintained in a 1-month follow-up assessment. However, no training gains were observed for the remaining 7 patients, thus questioning the generalizability of this method in enhancing memory in dementia. PMID- 1930768 TI - Effects of methanol vapor on human neurobehavioral measures. AB - Methanol could become an important motor fuel. The objective of this exploratory study was to provide preliminary information about whether or not acute exposure to methanol at 250 mg/m3 for 75 minutes would have adverse effects on human neurobehavioral functions important in everyday life. This concentration level was selected because it is at the upper limit of the traffic scenario estimates provided by the U.S. Environmental Protection Agency (EPA)2 (86 to 240 mg/m3), but is below the maximum concentrations for eight-hour average exposures currently recommended by the National Institute of Occupational Safety and Health (NIOSH) and the American Conference of Government and Industrial Hygienists (ACGIH) (260 mg/m3). Although traffic scenario exposure estimates suggest that such high levels of exposure last less than 15 minutes, we used a 75-minute exposure to increase the probability of identifying dependent measures that should be studied in more detail in a future confirmatory study. Twelve healthy young men, each serving as his own control, participated in two sham exposures and two methanol exposures under counterbalanced, double-blind control conditions. Because methanol is present in many foods, and because high preexposure levels of methanol or formate might obscure exposure effects, subjects were required to strictly limit their diets for 12 hours before each experimental session. The following endpoints were examined before, during, and after exposure to methanol and sham vapors: blood and urinary methanol; plasma formate; oral temperature; blood pressure; subjective mood, alertness, fatigue, workload, and symptom scales; spectral analysis of the electroencephalogram; visual- and auditory-event-related potentials; contingent negative variation; respiration; cardiac interbeat interval; Symbol Digit substitution task; three choice reaction time; Stroop color-word test; simple reaction time; visual function; critical flicker fusion frequency; hand steadiness; visual search task; Gamberale reaction time task; visual tracking task; Sternberg memory task; interval production task; and speeded addition task. Two dual tasks were also included in the task batteries. These endpoints were selected from those indicated in the literature to be sensitive to solvents, and from those that are widely used in other neurobehavioral test batteries to identify the effects of environmental pollutants. Because the number of endpoints examined was large and the number of subjects was small, procedures designed to reduce the number of statistical tests performed were used. Mean methanol concentration in the exposure room during methanol exposures was 249 mg/m3 (SD +/- 7 mg/m3). Exposure produced significant increases in blood and urine methanol concentration. As expected, no changes in plasma formate were observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1930769 TI - Mechanisms of nitrogen dioxide toxicity in humans. AB - These studies were undertaken to evaluate short-term respiratory effects and identify markers of nitrogen dioxide toxicity during exposures designed to approximate realistic conditions. With the development of bronchoalveolar lavage as a clinical investigative technique, the evaluation focused on the assessment of effects induced at the alveolar level. The exposure protocols were designed to assess the duration of nitrogen dioxide-induced effects and determine exposure response relationships. Groups of normal, nonsmoking volunteers of both sexes between the ages of 18 and 40 years, without airway hyperreactivity, constituted the study population. The exposure protocols required a total of three to five days for each subject, depending on the timing of bronchoalveolar lavage. Subjects were exposed to nitrogen dioxide or air for three hours in a double blind, randomized fashion in a 45-m3 environmental chamber, with intermittent exercise sufficient to quadruple minute ventilation. Pulmonary function was measured during and after exposure, and airway reactivity to carbachol was assessed before and after exposure. Lavaged cells were examined for their capacity to inactivate influenza virus and secrete IL-1 in vitro. Cell-free lavage fluid was analyzed for total protein, albumin, alpha 2-macroglobulin, arylsulfatase, and alpha 1-protease inhibitor. The studies were undertaken in three phases, each of approximately one year's duration. In Phase 1, 15 subjects were exposed to a background concentration of 0.05 parts per million2 (ppm) nitrogen dioxide and to three 15-minute peaks of 2.0 ppm, and underwent bronchoalveolar lavage 3.5 hours after nitrogen dioxide exposure. During Phase 2, 8 subjects were exposed to continuous 0.60 ppm nitrogen dioxide and underwent bronchoalveolar lavage 18 hours later. Finally, in Phase 3, 15 subjects were exposed to continuous 1.5 ppm nitrogen dioxide and underwent bronchoalveolar lavage 3.5 hours after exposure. No significant symptomatic or pulmonary function changes could be detected in response to any of the nitrogen dioxide exposures. However, a small but significant increase in airway reactivity was observed in normal subjects after exposure to 1.5 ppm nitrogen dioxide. Following the highest dose of carbachol (10 mg/mL), the forced expiratory volume in one second decreased 7.5 +/- 1.1 percent after nitrogen dioxide exposure compared to 4.8 +/- 1.1 percent after exposure to air (p less than 0.05). No symptoms were induced in any of the groups by the carbachol exposures. Analyses of cells recovered by bronchoalveolar lavage during all three phases revealed no differences in total cell recovery, cell viability, or differential cell counts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1930770 TI - Activation of cytotoxic cells in hyperplastic lymph nodes from HIV-infected patients. AB - Serine esterase B (SE B) is a protein contained in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells; SE B gene is transcribed upon activation of these cytotoxic cells. In order to show the in vivo interactions between HIV-infected cells and anti-HIV cytotoxic cells we analysed, by in situ hybridization, the expression of the SE B gene in eight hyperplastic lymph nodes from HIV-1-infected patients presenting with persistent generalized lymphadenopathy. We detected numerous cells expressing the SE B gene. The mean number of positive cells was 3.2 times higher in HIV lymph nodes than in six non HIV hyperplastic lymph nodes studied in parallel (P less than 0.05). In control lymph nodes, the SE B gene was expressed only in interfollicular areas; virtually no cells expressed the SE B gene within follicles. In contrast, in HIV lymph nodes cells expressing the SE B gene were distributed either in interfollicular areas or within follicles. Expression of the SE B gene inside follicles was thus a specific feature of HIV lymph nodes (P less than 0.001) and was associated with the presence of HIV antigens and RNA at the same site. These results suggest that cytotoxic cells are activated in follicles of HIV lymph nodes and may be involved in the lysis of HIV-infected cells. Such a phenomenon may explain the development of follicle lysis, a specific feature of HIV lymph nodes. It may also inhibit the spreading of HIV infection. PMID- 1930771 TI - Pentamidine aerosol increases the number of alveolar macrophages in HIV-infected patients. AB - In order to determine the possible effect of aerosolized pentamidine on the cellular composition of the bronchoalveolar lavage fluid in HIV-infected patients, differential counts of 22 consecutive patients who had been rebronchoscopied after 3-19 months were reviewed. Eleven patients were started on pentamidine prophylaxis subsequent to their first presentation. Eleven patients had never taken pentamidine or had discontinued the prophylactic regimen. Compared to first bronchoscopy, the bronchoalveolar lavage (BAL) from patients on regular prophylaxis revealed a significant increase in absolute alveolar macrophage (AM) counts at second presentation (20.8 +/- 11.2 to 50.3 +/- 39.4 x 10(5) cells/100 ml BAL; P less than 0.01). The AM counts of those without pentamidine remained essentially unchanged. Lymphocytes, including CD4 and CD8 subtypes, and neutrophils did not change over time in either group. The results of this retrospective analysis suggest that, in addition to its antimicrobial action, pentamidine may modulate local lung defence mechanisms, particularly by increasing the absolute number of AM. PMID- 1930772 TI - Psychosocial factors and disease progression in simian AIDS: a preliminary report. AB - Infection of macaques by the simian immunodeficiency virus (SIV), like HIV infection in humans, results in a variable time course to clinical disease. Developmental studies of macaques have shown that psychosocial disruption, including social separations, can result in both immediate and long-term immunological consequences. Using colony records on a subset of rhesus macaques (Macaca mulatta) inoculated with SIV at the California Primate Research Center, Davis, California, USA, we constructed regression equations to determine whether the animals' psychosocial histories could explain any of the variability observed in measures of disease progression. After controlling for dosage, age at inoculation, sex, and previous inoculation history, psychosocial variables were found to be significantly associated with several indicators of disease, including latencies to display leukopenia and lymphopenia, weight loss, and survival. We believe these preliminary results suggest an important role for psychosocial processes in affecting disease progression in SIV infection in macaques. PMID- 1930773 TI - HIV and child-bearing: clinical outcome and aspects of mother-to-infant transmission. AB - Forty-four HIV-1-seropositive women and their children were followed-up and examined in connection with the course of pregnancy, mother-to-infant transmission of HIV and clinical outcome. Twelve out of 48 children were known to be infected and two children were lost to follow-up. Of the remaining 34 children, 22 are not infected, and 12 are clinically and immunologically normal at less than 18 months. There was no difference in intrauterine growth between infected and uninfected children. Forty-six per cent of the 39 mothers seen after delivery progressed to a more advanced stage of HIV infection during a mean follow-up time of 33 months after delivery. Although comparable in age, clinical and immunological status at delivery, and follow-up time, mothers of infected children had longer durations of HIV infection and were symptomatic and/or had low CD4 cell counts to a significantly greater extent at follow-up than mothers of uninfected children. PMID- 1930774 TI - Cognitive abnormalities and disease progression in a selected population of asymptomatic HIV-positive subjects. AB - A selected population of 41 homosexual/bisexual asymptomatic HIV-positive subjects were administered neurophysiological tests to assess language, memory, attention, logic faculties and visuo-motor functions. HIV-positive subjects differed from individually matched control subjects only in certain measures of verbal memory. Longitudinal evaluation performed after 1.5 years, however, did not indicate any further development of this mild amnesic deficit. Despite the small number studied in our sample, there seems to be a trend for older subjects to be at greater risk of developing AIDS and cognitive abnormalities than younger subjects, while differences in immunological status play a significant role in disease progression. PMID- 1930775 TI - Heterosexual transmission of HIV-1 associated with the use of smokable freebase cocaine (crack). AB - A study of risk factors for HIV-1 infection was conducted at a sexually transmitted disease clinic in an area of New York City where the cumulative incidence of AIDS in adults through mid-1990 was 9.1 per 1000 of the population and where the use of illicit drugs, including smokable freebase cocaine (crack), is common. The overall seroprevalence among volunteers was 12% (369 out of 3084), with 80% of those who were seropositive reporting risk behavior associated with HIV-1 infection, including male-to-male sexual contact, intravenous drug use and heterosexual contact with an intravenous drug user. The seroprevalence in individuals denying these risks was 3.6% (50 out of 1389) and 4.2% (22 out of 522) in men and women, respectively. Among these individuals, the behaviors significantly associated with infection were use of crack and prostitution in women, and history of syphilis and crack use in men. These results suggest that in areas where the level of HIV-1 infection in heterosexual intravenous drug users is high and the use of crack is common, increased sexual activity (including the exchange of drugs or money for sex) may result in increased heterosexual transmission of HIV-1. PMID- 1930776 TI - Risk factors for HIV-2 infection in The Gambia. AB - A serosurvey was carried out to assess the prevalence of HIV infection in The Gambia and the importance of possible risk factors. The overall prevalence of HIV 2 infection among the 4228 adults studied was 1.7% while that of HIV-1 was 0.1%. The prevalence of HIV-2 was similar in both sexes but higher among those greater than 25 years of age and those who lived in two small towns along a main transport route. Among men, multivariate analysis showed prevalence of HIV-2 infection was significantly greater among those in the more affluent occupations, those without a secondary education and those with a history of urethral discharge. Among women, infection was more frequent in divorcees and widows and those who had been married several times. The prevalence was also higher in individuals born in Guinea-Bissau and in an ethnic group which originated there. PMID- 1930777 TI - HIV-1 infection among New York City inmates. AB - A blinded seroprevalence survey for HIV-1 infection was conducted among individuals entering New York City (NYC) prisons in 1989. Data collected included age group, race/ethnicity, syphilis serologic results and self-admitted drug use. Remnant serum specimens were tested for HIV-1 antibody by enzyme-linked immunosorbent assay and confirmed by Western blot. Of 2236 inmates surveyed, 413 (18.5%) were HIV-1 positive. Rates varied by subgroup, and were higher for women than men (25.8 versus 16.1%; odds ratio 1.8; P less than 0.01), for drug users than inmates who denied drug use (25 versus 14%; odds ratio 2.3; P less than 0.01), for intravenous heroin users (43 versus 15% in drug users not using heroin), and for inmates with positive rapid plasma reagin test (RPR) results (34.5 versus 16.1% in RPR-negative inmates). Use of intravenous heroin was most strongly related, by logistic regression, to HIV-1 seropositivity. The results are among the highest found in US inmates, and suggest that there were 12,500 seropositive individuals incarcerated in 1989. This represents approximately 10% of the estimated number of seropositive individuals in NYC. The NYC Correctional System should be viewed as a front-line institution in the fight against AIDS through provision of HIV-related prevention services and clinical care, and drug treatment. PMID- 1930778 TI - Increased interleukin-6 production is associated with disease progression in HIV infection. PMID- 1930779 TI - Serum antibody directed against synthetic peptides derived from HIV-1 protein sequence obtained from 26 Japanese HIV-1-infected individuals. PMID- 1930780 TI - Evidence for beneficial effect of recombinant interleukin-2 in HIV-associated B lymphoma. PMID- 1930781 TI - Non-Hodgkin's lymphoma among homosexual men and intravenous drug users with AIDS in Italy. PMID- 1930783 TI - Rapidly reversible cardiomyopathy in an AIDS patient. PMID- 1930782 TI - Acute HIV seroconversion and pneumonitis. PMID- 1930784 TI - Paromomycin for the treatment of cryptosporidial diarrhoea in AIDS patients. PMID- 1930785 TI - HIV-1 seroprevalence in patients presenting with sexually transmitted disease (STD): results from six Parisian STD clinics. PMID- 1930786 TI - Using forensic techniques to verify self-reports of needle-sharing. PMID- 1930787 TI - Trichosanthin treatment of HIV disease. PMID- 1930788 TI - The ultimate reminiscence. PMID- 1930789 TI - In touch with reality. PMID- 1930790 TI - Dressing leg ulcers. PMID- 1930791 TI - Community clinics. PMID- 1930792 TI - Hassles of caring. PMID- 1930793 TI - Visionary work. PMID- 1930794 TI - Leading questions. PMID- 1930795 TI - As I was saying.... PMID- 1930796 TI - A hidden workforce. PMID- 1930797 TI - Home from home. PMID- 1930798 TI - Over the rainbow. PMID- 1930799 TI - Commitment. PMID- 1930800 TI - Diabetes insipidus and syndrome of inappropriate secretion of antidiuretic hormone in children with midline suprasellar brain tumors. AB - Salt and water balance within the body is controlled by the hormonal influence of vasopressin. Vasopressin is produced in the hypothalamus, stored and released from the posterior lobe of the pituitary, and travels via the blood to the kidneys to regulate the amount and concentration of urine excreted. Oversecretion or undersecretion of vasopressin, eg, diabetes insipidus (DI) or syndrome of inappropriate secretion of antidiuretic hormone (SIADH) results in an imbalance of the salt-to-water ratio. In children this hormonal imbalance may occur secondary to a suprasellar brain tumor and/or the treatment of such. Approximately 50% to 75% of children with suprasellar tumors will develop permanent DI and the remainder will experience transient postoperative DI or SIADH. Pathophysiology of vasopressin's control on salt and water balance and its relationship to suprasellar brain tumors in children are presented. Nursing assessment and intervention parameters for management of DI and SIADH in children with brain tumors are also discussed. PMID- 1930801 TI - Informed consent for treatment of childhood cancer: factors affecting parents' decision making. AB - Both the treatment for childhood cancer and the legal requirements for gaining parents' consent to treatment have become increasingly complex. The purpose of the exploratory investigation reported here was to identify influential circumstances surrounding the consent process in the pediatric setting, to describe the relationship of parental anxiety to these factors, and to delineate related practice and research implications. Twenty-eight parents of children entered on one of four protocols for the treatment of newly diagnosed acute lymphoblastic leukemia at the Childrens Hospital Los Angeles and the University of California San Francisco were asked to complete two questionnaires within 48 hours after consenting to treatment: the State-Trait Anxiety Index and the Parent Informed Consent Questionnaire. Results of the study confirmed clinical experience that parents are given complex information and asked to make decisions about their child's life in a highly anxious state. Although participants were generally satisfied with the informed consent process 48 hours after signing a consent form, further research is needed to document how well parents understand and remember key information, as well as the influence of time, experience, and changes in state anxiety on their perceptions of the adequacy of the consent process. In current clinical practice, simple strategies can be applied to improve the informed consent process for families of children with cancer. PMID- 1930802 TI - Validity and reliability of a pediatric hematology oncology patient acuity tool. AB - Appropriate use of nursing resources in the pediatric hematology and oncology inpatient settings demands a patient acuity system that is easy to use and accurate, and that objectively measures nursing care needs of a specialized patient population. Structured survey of 13 comprehensive cancer centers and a review of the literature show no valid and reliable acuity tools for this pediatric population. The purpose of this project was to study the validity and reliability of a newly developed pediatric hematology and oncology acuity system designed to quantify patient care needs. A new acuity tool for this pediatric population was developed based on the patient classification tool used at Johns Hopkins Hospital Oncology Center (JHHOC). The levels of care from the JHHOC tool were adopted, with therapeutic indicators modified to reflect nursing diagnoses relevant to the pediatric inpatient. Nursing care hours required for each level of care were also identified. Validity was studied using a content validity index (CVI). Experts from the pediatric unit where the tool would be used were asked whether each therapeutic indicator was assigned to the correct level of care (1 thru 5) based on patient care hours. CVIs for items ranged from .5 to 1.0; the overall CVI for the tool was .93. Interrater reliability was studied using two raters from the unit. Data were collected for 150 patient observations on a 12 bed pediatric hematology and oncology inpatient and short-stay outpatient unit. The resulting Pearson correlation coefficient was r = .97 (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930803 TI - Measurement of pain: self-report strategies. AB - There are many options available to measure a child's self-report of pain. Many factors should be considered when choosing a scale, including previous testing, ease of administration, age of the child, and type of pain experience. When selecting a measure, it is important to pretest it with a sample similar to that in the proposed study to evaluate these factors. PMID- 1930804 TI - Granulocyte-macrophage colony-stimulating factor. PMID- 1930805 TI - A systematic approach to preparing for chemotherapy administration. PMID- 1930806 TI - Taking risks. PMID- 1930807 TI - Measles epidemic: impact on pediatric oncology patients. AB - Measles, a preventable disease, is again epidemic in the United States and is a threat to the immunocompromised pediatric oncology patient. In response to this latest epidemic, the Immunization Practices Advisory Committee has revised its recommendations for controlling an outbreak and has changed childhood immunization to a two-dose schedule. Full understanding of measles management is needed to effectively protect the pediatric oncology patient during the current epidemic. This article reviews the epidemiology, clinical presentation and management of measles, including recommendations for vaccinations, exposures, isolation, and patient and family education. PMID- 1930808 TI - An investigation of the safety of the blood reinfusion step used with tunneled venous access devices in children with cancer. AB - Infection has been identified as the most serious potential complication of the indwelling catheter. As a result, the primary nursing goal using the catheters is to prevent infection. Nurses must frequently manipulate the catheters when securing blood specimens and are concerned that this manipulation may serve as a source of infection for the immunocompromised pediatric oncology patient. One particular step in catheter manipulation during blood sampling is blood reinfusion, ie, residual blood in the catheter is withdrawn and set aside while a second sample is collected for laboratory analysis but is subsequently returned to the patient through the catheter. The purpose of this study was to examine this nursing procedure for its potential of contaminating the blood sample that was to be reinfused, or for the potential of reinfusing a sample that contained preexisting pathogens independent of the procedure itself. An experimental design was used with 21 patients randomly assigned to an experimental group (unclean procedure to exaggerate the potential to incur pathogens during the process), and 21 randomly assigned to a control group (usual clean procedure followed with the reinfusion sample). The usual blood sampling procedure was altered for all participants as the typical amount of blood that normally constitutes the reinsertion sample was not reinserted, but was instead used to complete certain microbial analyses. Of the 42 participants, 17 were male and 25 were female; 35 were white and seven were black; 22 were diagnosed with leukemias and 20 with solid tumors. The age range for participants was 2 to 20 years (mean = 9.4 years, SD = 4.8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930809 TI - Sexual concerns of adolescents with cancer. AB - The sexually related concerns of adolescents with cancer were compared with those of healthy adolescents. Forty-one adolescents age 12 to 19 years participated. A sexual concerns questionnaire was used. The study had three primary objectives: (1) to identify concerns related to physical, emotional, and behavioral aspects of sexuality present among all adolescents in the study; (2) to determine if there were differences between sexual concerns of adolescents with cancer and those of healthy adolescents; and (3) to determine whether a relationship existed between age and the concerns adolescents had about sexuality. Results of the study indicate that although no age-linked trends in sexually related concerns existed for the adolescents studied, adolescents had concerns regarding sexuality. Adolescents with cancer did not seem to be any more concerned about common developmental aspects of sexuality than healthy adolescents. However, adolescents with cancer had numerous sexually related concerns not identified by healthy adolescents. These concerns seem to relate to being treated for cancer. They included worries about hair loss, feeling isolated, ability to have children, and children having genetic or congenital defects. Nurses who care for adolescents with cancer can provide education and support regarding sexual concerns to help adolescents cope with and resolve some of these treatment related anxieties. Further research that includes in-depth, narrative interviews could give better insight into the concerns that both adolescents with cancer and healthy adolescents have about sexual issues. PMID- 1930810 TI - Changing central venous catheter lines: evaluation of a modification to clinical practice. AB - As the costs of providing quality nursing care increase, the conservation of both human and material resources becomes increasingly important. This study arose from a need to evaluate the procedure used to change central venous catheter (CVC) lines following the substitution of a time-consuming and costly traditional procedure with a simpler procedure that used less resources. Using a convenience sample of inpatients in the oncology unit who had either fully or partially implanted infusion devices in situ, rates of infection for CVC exit sites were calculated for the 12-month periods preceding and following the introduction of the revised procedure. No significance differences were found between the infection rates at CVC line exit sites; however, the cost of undertaking the procedure decreased following a change of equipment used in the line-change procedure. Data collection methods are discussed, together with results and implications for clinical practice. PMID- 1930811 TI - Measurement of behavioral response to pain. PMID- 1930812 TI - Helping parents understand diagnostic and treatment conference information. PMID- 1930813 TI - Structure of cis-1-([4-(1-imidazolylmethyl)cyclohexyl]methyl)imidazole- succinic acid complex. AB - CGS 14796C, C14H20N4.C4H6O4, Mr = 362.43, monoclinic, C2/c, a = 28.148 (4), b = 9.722 (1), c = 19.200 (2) A, beta = 133.06 (1) degree, V = 3838.88 A3, Z = 8, Dx = 1.26 Mg m-3, lambda (Cu K alpha) = 1.5418 A, mu 0.702 mm-1, F(000) = 1552, T = 294 K, R = 0.075 for all 3285 reflections. The structure is composed of linear chains of alternating CGS 14796C and succinic acid molecules. The CGS 14796C molecule is in an extended conformation. PMID- 1930814 TI - A highly propeller-twisted adenine-adenine base pair in 8-tert-butyladenine. AB - C9H13N5, Mr = 191.24, monoclinic, P2(1)/c, a = 7.562 (1), b = 6.825 (1), c = 20.905 (1) A, beta = 104.84 (1) degree, V = 1042.9 A3, Z = 4, room temperature, Dx = 1.218 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 6.6 cm-1, F(000) = 408. The structure was solved by the multisolution technique and refined by the block diagonal least-squares method to a final R index of 0.045 using 1970 intensities. The adenine bases form three pairs of hydrogen bonds to symmetry-related molecules in the crystal lattice. Two distinct modes of hydrogen bonding are observed. One mode involves a planar interaction between adjacent adenine bases while the second mode is characterized by an unusually high propeller twist angle of 79.3 degrees between the planes through the two participating adenine bases. PMID- 1930815 TI - Structure of chloro(dicyclohexylphenylphosphine)gold(I). AB - [AuCl(P(C6H5)(C6H11)2)), Mr = 506.8, orthorhombic, P2(1)2(1)2(1), a = 8.476 (5), b = 13.747 (2), c = 15.951 (3) A, V = 1858.8 (3) A3, Z = 4, Dx = 1.81 g cm-3, lambda (Mo K alpha) = 0.71073 A, mu = 81.24 cm-1, F(000) = 984, T = 296 K, final R = 0.031 for 1860 unique observed reflections. The complex Cy2PhPAuCl adopts the two-coordinate linear geometry typical of AuI complexes. The P-Au-Cl angle is 178.3 (1) degrees while Au-P and Au-Cl distances are 2.234 (2) and 2.281 (3) A, respectively. The geometry of the P atom is tetrahedral with an average Au-P-C angle of 112.1 (3) degrees and an average P-C distance of 1.827 (8) A. PMID- 1930816 TI - Structure of 3-hydroxy-17-oxoestra-1,3,5(10)-trien-11 beta-yl acetate. AB - C20H24O4, Mr = 328.41, orthorhombic, P2(1)2(1)2(1), a = 11.688 (3), b = 15.377 (5), c = 9.466 (2) A, V = 1701 (1) A3, Z = 4, Dx = 1.282 g cm-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.823 cm-1, F(000) = 704, T = 298 K, R = 0.063 for 1921 reflections with F greater than 2 sigma (F). The structure was determined to observe the effect of the 11 beta-acetate substituent on the conformation of the molecule. The 3-hydroxy is hydrogen bonded to O19 at 2.86 A. The B ring has a 7 alpha, 8 beta-half chair conformation, the most commonly observed B ring conformation in estrogen analogues. PMID- 1930817 TI - Structure of 9 beta-estrone. AB - 3-Hydroxy-9 beta-estra-1,3,5(10)-trien-17-one, C18H22O2, Mr = 270.4, monoclinic, P2(1), a = 9.527 (2), b = 11.182 (3), c = 7.078 (1) A, beta = 108.45 (1) degrees, V = 715.3 (3) A3, Z = 2, Dx = 1.255 g cm-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.746 cm-1, F(000) = 292, T = 298 K, R = 0.037 for 2128 reflections with F greater than 2.0 sigma (F). The compound was one in a series of 9 beta-estrone analogues synthesized to study their estrogenic activity. The B ring conformation is a 7 beta,8 alpha-half chair, due to the configuration at C9. The O3 hydroxy forms a hydrogen bond to O17 at a distance of 2.76 A. PMID- 1930818 TI - Structure of a fully protected seco-erythronolide B acid derivative. AB - (3S,4R,5S,6R,7R,9R,10S,11S,12S,13S,- 14R)-14-Benzyloxymethoxy-10,12-O-carbonyl-4 N- imidazolylcarbonyl-6,7-O-isopropylidene-3,5,7,9,11,- 13-hexamethylhexadec-1 ene-4,6,7,10,12,14-hexol, C38H56N2O9, Mr = 684.87, monoclinic, P2(1), a = 8.7302 (12), b = 15.597 (2), c = 14.463 (2) A, beta = 104.797 (10) degrees, V = 1904.1 (4) A3, Z = 2, Dx (198 K) = 1.19 g cm-3, mu = 0.7893 cm-1, Mo K alpha radiation, lambda = 0.7107 A, F(000) = 740, T = 198 K, R = 0.0301 for 3141 reflections [Fo greater than or equal to 4 sigma (Fo)]. The crystal structure was undertaken to determine the stereochemistry of the title compound. The molecule is folded on itself in such a way that the portion of the molecule from the phenyl ring at C44 and extending to C28 forms nearly a single turn of a right-handed screw. Large deviations from ideality for several Csp3-Csp3 bond angles are observed that are presumably due to intramolecular steric effects. The largest deviations are: C3 C4-C5 117.8 (2), C5-C6-C7 121.2 (2), C7-C8-C9 115.3 (2), C9-C10-C11 116.2 (2), C11-C12-C13 117.2 (2), C14-C15-C16 115.5 (3) degrees. PMID- 1930819 TI - Structure of (+/-)-(2S,1'S)-2-[hydroxy(phenyl)methyl]-2-methylcyclohexanone, C14H1802. AB - Mr = 281.30, monoclinic, P2(1)/n, a = 10.966 (4), b = 7.170 (3), c = 15.976 (4) A, beta = 93.14 (2) degrees, V = 1254.3 (9) A3, Z = 4, Dx = 1.16 g cm-3, lambda (Mo K alpha) = 0.71069 A, mu = 0.706 cm-1, F(000) = 472, T = 295 K, final R = 0.057 for 1212 unique observed reflections. The compound was prepared by reaction of the trichlorotitanium-delta 1(2)-enolate of 2-methylcyclohexanone with benzaldehyde. PMID- 1930821 TI - Platelet activating factor antagonists. Structure of N,N'-bis(3,4,5 trimethoxybenzoyl)-2-piperazinylmethyl 2,2-dimethylpropanoate. AB - Racemic title compound, C30H40N2O10, Mr = 588.65, triclinic, P1-, a = 10.154 (7), b = 11.820 (9), c = 15.038 (8) A, alpha = 96.02 (5), beta = 1.07.54 (4), and gamma = 110.34 (5) degrees, V = 1569 (2) A3, Z = 2, Dx = 1.25 g cm-3, Cu K alpha, lambda = 1.5418 A, mu = 7.4 cm-1, F(000) = 628, T = 293 K, R = 0.0470, wR = 0.0481 for 1961 unique observed reflections. The piperazine ring adopts a chair conformation and the molecule shows limited flexibility of the pseudo-twofold related trimethoxybenzoyl moieties. The planes through the piperazine and the two trimethoxyphenyl rings are oriented almost perpendicular to each other. Apart from a few possible weak hydrogen bonds, the molecules are held together by weak pi overlap and van der Waals forces. PMID- 1930820 TI - (4,4'-Dimethyl-2,2'-bipyridyl-N,N')bis(isocyanato)platinum(II). AB - [Pt(NCO)2(C12H12N2)], Mr = 463.37, orthorhombic, Cmc2(1), a = 18.722 (6), b = 11.889 (5), c = 6.688 (5) A, V = 1488.7 (9) A3, Z = 4, Dx = 2.067 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 90.59 cm-1, F(000) = 864, T = 291 (1) K, R = 0.052 for 735 reflections with F greater than or equal to 6 sigma F. The structure consists of square-planar coordinated Pt atoms, surrounded by four N atoms; of these, two belong to the bidentate bipyridyl ligand and two belong to the two pseudohalide groups which occupy cis positions. The bite angle of the bipyridyl ligand is 82.3 (9) degrees, significantly larger than the value reported earlier for the unsubstituted bipyridyl ligand, 76 (2) degrees. The metal atom is displaced 0.10 (5) A below the plane of the four N atoms. The non bonding Pt-Pt distance is 0.258 (5) A longer in the title compound than in the unsubstituted ligand complex, leading to significant differences in the chemical and spectroscopic properties of the two homologues. PMID- 1930823 TI - Structure of nortriptyline hydrochloride. AB - C19H22N+.Cl-, Mr = 299.84, monoclinic, P2(1)/c, a = 5.070 (2), b = 34.088 (5), c = 9.976 (1) A, beta = 90.74 (2) degrees, V = 1724.0 A3, Z = 4, Dx = 1.16 g cm-3, lambda (Mo K alpha 1) = 0.70930 A, mu = 2.2 cm-1, F(000) = 640, T = 295 K, final R = 0.046 for 1381 observed reflections. The nortriptyline molecule crystallized with a 'butterfly' fold angle of 124.3 (2) degrees and an extended propylamino side chain. The amino nitrogen is involved in hydrogen bonds to two different chloride ions. PMID- 1930822 TI - Structure of thialysine hydrochloride. AB - 2-Ammonio-3-[(2-ammonioethyl)thio]propionate chloride, C5H13N2O2S+.Cl-, Mr = 200.7, monoclinic, P2(1), a = 5.1275 (4), b = 7.897 (1), c = 11.208 (1) A, beta = 104.129 (8) degrees, V = 440.1 A3, Z = 2, Dx = 1.519 g cm-3, Mo K alpha, lambda = 0.71069 A, mu = 6.12 cm-1, F(000) = 212, T = 295 K, final R = 0.021, wR = 0.027 for 784 reflections with I greater than 3 sigma (I). The two ammonium cations form seven hydrogen bonds: alpha-NH3+ acts as a donor for three carboxylate O atoms and one Cl- ion whereas epsilon-NH3+ is linked to three Cl- ions. PMID- 1930824 TI - Conformation of cyclic octapeptides. VI. Structure of cyclo-bis-(-L-alanyl-glycyl L-prolyl-L-phenylalanyl-) tetrahydrate. AB - C38H48N8O8.4H2O, Mr = 816.9, monoclinic, P21, a = 10.381 (1), b = 13.273 (1), c = 15.742 (1) A. beta = 101.83 (1) degree, V = 2123.1 A3, Z = 2, Dx = 1.278 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 7.6 cm-1, F(000) = 872, R = 0.035, wR = 0.045 for 3497 reflections [I greater than 2 sigma (I)], 4552 unique reflections measured. The synthetic cyclic octapeptide crystallizes from water/methanol solution as a tetrahydrate and the crystals are isomorphous to those of the disulfide-bridged cystine analog cyclo-bis(-L-Cys-Gly-L-Pro-L-Phe-) [Kopple, Wang, Cheng & Bhandary (1988). J. Am. Chem. Soc. 110, 4168-4176]. The coordinates of the Cys analog were taken as the starting coordinates for full-matrix least squares refinement. The cyclic octapeptide ring has two beta turns encompassing the residues Pro-L-Phe, one type I and the other type II, with all peptide links trans. The conformation of the cyclic octapeptide backbone is similar to the Cys analog; all backbone dihedral angles in the two molecules agree to within 6 degrees. This suggests that the disulfide bridge of the Cys analog does not impose any conformational constraint on the octapeptide ring backbone. PMID- 1930825 TI - Structure of benzyloxycarbonyl-L-isoleucyl-L-alanyl-alpha- aminoisobutyryl-alpha aminoisobutyrate methyl ester, Z-L-Ile-L-Ala-Aib-Aib-OMe. AB - C26H40N4O7, Mr = 520.6, tetragonal, P4(3)2(1)2, a = 10.433 (1), c = 54.476 (7) A, V = 5930 (1) A3, Z = 8, Dm = 1.155 (3), Dx = 1.166 Mg m-3, lambda (Cu K alpha) = 1.54178 A, mu = 0.665 mm-1, F(000) = 2240, T = 295 K, R = 0.057 for 2037 observed reflections. The tetrapeptide adopts a type II beta-turn conformation with an extremely weak 4----1 intramolecular hydrogen bond [3.479 (7) A]. The molecules are held together in the crystal by three kinds of N-H---O intermolecular hydrogen bonds. PMID- 1930827 TI - Proline conformations in linear peptides. Structure determination of the methyl ester of N-benzyloxycarbonyl-L-prolyl-D-alanine (N-Z-L-Pro-D-Ala-OMe). AB - N-Z-L-Pro-D-Ala-OMe, C17H22N2O5, Mr = 334.38, crystallizes in the orthorhombic space group P2(1)2(1)2(1), with the cell dimensions a = 5.005 (5), b = 17.690 (9) and c = 18.70 (1) A3, V = 1656.3 A3, Z = 4, Dx = 1.341 g cm-3, Cu K alpha, lambda = 1.54184 A, mu = 7.830 cm-1, F(000) = 712, T = 198 K, final R (on F) = 0.036 for 1575 observed reflections with I greater than or equal to 3 sigma(I). The pyrrolidine ring takes on the C2-C gamma-endo conformation. The urethane bond is in the cis conformation [omega 0 = 6.0 (3) degrees] while the peptide bond is in the trans conformation [omega 1 = 170.8 (2) degrees]; phi 1/psi 1 values are 88.0 (3) degrees and 151.3 (2) degrees. Intermolecular hydrogen bonding occurs between the C-terminus and the symmetry-related amide. Systematic examination of the pyrrolidine ring in linear peptides reveals no correlation exists between the cis-trans orientation of the proline and the conformation of the pyrrolidine ring. PMID- 1930826 TI - Structure of a new cyclotetrapeptide trapoxin A. AB - C34H42N4O6, Mr = 602.73, triclinic, P1, a = 14.707 (2), b = 15.559 (2), c = 13.026 (1) A, alpha = 112.23 (1), beta = 97.25 (1), gamma = 60.67 (1) degree, V = 2399.1 (6) A3, Z = 3, Dx = 1.251 Mg m-3, lambda(Cu K alpha) = 1.54178 A, mu = 0.71 mm-1, F(000) = 966, T = 295 K, R = 0.042 for 7802 observed reflections [Fo greater than 3 sigma (Fo)]. The structure of trapoxin A was determined as cyclo[ (S)-phenylalanyl-(S)-phenylalanyl-(R)-pipecolinyl- (2S,9S)-2-amino-8-oxo-9,10 epoxydecanoyl-]. There are three crystallographically independent molecules in the cell. These molecules are linked to each other by NH...O hydrogen bonds to form an infinite chain extending along the a axis. PMID- 1930828 TI - Structure of 18'-epivinblastine. AB - Methyl (3aR-[3a alpha,4 beta,5 beta,5a beta,9(3R*,5S*,7R*,9R*), 10bR,13a alpha]) 4-(acetyloxy)-3a-ethyl-9-[5-ethyl-1,4,5,6,7,8,9, 10-octahydro-5-hydroxy-9 (methoxycarbonyl)-2H-3,7- methanoazacycloundecino[5,4-b]indol-9-yl] 3a,4,5,5a,6,11,12, 13a-octahydro-5-hydroxy-8-methoxy-6-methyl-1H-indolizino-[8,1 c,d] carbazole- 5-carboxylate methanol solvate, C46H58N4O9. 2CH3OH (1), Mr = 875.07, monoclinic, P2(1), a = 10.2759 (12), b = 22.353 (3), c = 10.4051 (12) A, beta = 106.502 (9) degrees, V = 2291.6 (5) A3, Z = 2, Dx = 1.27 g cm-3, Mo K alpha radiation, lambda = 0.7107 A, mu = 0.8397 cm-1, F(000) = 940, T = 198 K, R = 0.0470 for 2751 reflections, Fo greater than or equal to 4 sigma(Fo). The C ring of the vindoline moiety is in the boat conformation with the hydroxy group and the tertiary N in the bowsprit positions resulting in a fairly short intramolecular hydrogen-bonding interaction. The relevant parameters for O3- H3...N9 are O...N 2.651 (6), H...N 1.94 (5) A and O--H...N 147 (5) degrees. The D and E rings are in the sofa and envelope conformations, respectively. The piperidine ring of the catharanthine portion of the molecule assumes the chair conformation while the conformation of the azacyclononene ring is a boat-chair. An intramolecular hydrogen bond between the indolino NH of the catharanthine moiety and methoxy O (O25) of the vindoline moiety is also observed. The relevant parameters for N16'--H16'...O25 are N...O 2.827 (6), H...N2.14 (6) A and O--H...N 136 (5) degrees. PMID- 1930829 TI - The structure at 198 K of (1R,5R,15R,16R)-5-isopropenyl-2-methyl- 1-[N-(trans-2 phenylcyclohexyloxycarbonyl)amino]-2-cyclohexene. AB - trans-2-Phenylcyclohexyl N-(5-isopropenyl-2-methyl-2-cyclohexan-1-yl) carbamate, C23H31NO2, Mr = 353.50, orthorhombic, P2(1)2(1)2(1), a = 8.813 (2), b = 9.043 (2), c = 25.643 (5) A, V = 2043.6 (8) A3, Z = 4, Dx = 1.15 g cm-3 (198 K), Mo K alpha radiation, lambda = 0.7107 A, mu = 0.6734 cm-1, F(000) = 768, T = 198 K, R = 0.0547 for 1772 reflections [Fo greater than or equal to 4 sigma(Fo)]. Molecules are H-bonded into infinite columns parallel to a. The H bond involves the NH group and the carbonyl O atom of the carbamate moiety with relevant parameters: N11-H11...O13 (related by 1/2 + x, 1/2 - y, - z); N...O 2.910 (5), H...O 2.11 (5) A, N-H...O 159 (4) degrees. PMID- 1930830 TI - Structure of tetraaquacopper(II) chlorate at 296 and 223 K. AB - [Cu(H2O)4](ClO3)2, Mr = 302.51, orthorhombic, Pbca, lambda (Mo K alpha) = 0.71069 A, Z = 4, F(000) = 604; T = 296 K, a = 12.924 (3), b = 9.502 (2), c = 7.233 (1) A, V = 888.3 (3) A3, D chi = 2.26 g cm-3, mu = 31.04 cm-1, R = 0.041 for 1174 unique reflections with I greater than sigma (I); T = 223 K, a = 12.853 (2), b = 9.492 (2), c = 7.216 (2) A, V = 880.4 (3) A3, D chi = 2.28 g cm-3, mu = 31.28 cm 1, R = 0.033 for 1279 unique reflections with I greater than sigma (I). The single type of copper ion is octahedrally coordinated by four water oxygens and two chlorate ion oxygens; the complex is characterized by three distinct pairs of Cu-O distances (which we have previously described as '2 + 2 + 2' coordination), one of which is substantially larger than the remaining two. The nominal 90 degrees O-Cu-O angles of the complex differ from that value by at most +/- 1.8 degrees. The observed structure of the complex is typical for copper(II) and is consistent with the Jahn-Teller effect. The single type of chlorate ion shows the expected trigonal pyramidal geometry, with average Cl-O bond lengths 1.485 (13) and 1.490 (11) A and average O-Cl-O bond angles 106.8 (13) and 106.8 (13) degrees for 296 and 223 K, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930831 TI - Histidyl conformations and short N-H...N hydrogen bonds: structure of D,L histidyl-L,D-histidine pentahydrate. AB - D,L-Histidyl-L,D-histidine pentahydrate, C12H16-N6O3.5H2O, Mr = 382.38, F(000) = 408, crystallizes in the monoclinic space group Pc with the cell dimensions a = 9.971 (2), b = 4.745 (2), c = 19.572 (3) A and beta = 96.08 (1) degree, V = 920.6 A3, Z = 2, D chi = 1.379 g cm-3. mu = 1.083 cm-1, T = 295 K, Mo K alpha, lambda = 0.71073 A. Final R (on F) = 0.040 for 1658 observed reflections with I greater than or equal to 3 sigma (I). This dipeptide crystallizes in a zwitterionic form with protonation of the C-terminal imidazole ring. Both histidine units exist in the g+ or 'closed' conformation with C alpha-C beta torsion angles of 67.2 (3) and 63.6 (3) degrees. Principal torsion angles, omega = 176.8 (2). psi 1 = 161.8 (3) and phi 2 = -152.1 (3) degrees, are indicative of a highly extended trans conformation. Intramolecular hydrogen bonding occurs between the imidazole rings [N2D-H2D1...N1D = 2.724 (4) A]. Intermolecular hydrogen bonding occurs between symmetry-related histidine molecules forming chains along the gamma axis and includes another short [2.764 (4) A] N-H...N interaction. The five water molecules occupy channels between adjacent histidine layers. PMID- 1930832 TI - Structural comparison of a gem-dichlorodiarylcyclopropane antiestrogen and three of its derivatives. AB - The pure antiestrogenic activity of compound (1) gave the impetus to synthesize a series of its derivatives (2)-(4). Structural features of these compounds are compared. Compound (1): 1,1-dichloro-cis-2,3-diphenylcyclopropane, C15H12Cl2, Mr = 263.2, orthorhombic, Pbca, a = 19.627 (7), b = 19.460 (6), c = 6.670 (2) A, V = 2547.5 A3, Z = 8, D chi = 1.372 g cm-3, lambda (MoK alpha) = 0.71069 A, mu (Mo K alpha) = 4.3 cm-1, F(000) = 1088, T = 138 K, R = 0.026 for 1923 observed reflections. Compound (2): 1,1-dichloro-cis-2,3-bis(4-methoxyphenyl)cyclopropane, C17H16Cl2O2, Mr = 323.2, monoclinic, P2(1)/C, a = 16.540(1), b = 7.4749(7), c = 12.333 (3) A, beta = 91.53 (2) degrees, V = 1524.2 A3, Z = 4, D chi = 1.408 g cm 3, lambda (Cu K alpha) = 1.54178 A, mu (Cu K alpha) = 37.0 cm-1, F(000) = 672, T = 163 K, R = 0.031 for 2919 observed reflections. Compound (3): 1,1-dichloro-cis 2-(4-benzyloxyphenyl)-3-phenylcyclopropane, C22H18Cl2O, Mr = 369.3, monoclinic, P2(1)/alpha, a = 21.064 (3), b = 14.749 (2), c = 5.8222 (8) A, beta = 95.48 (2) degrees, V = 1800.5 A3, Z = 4, D chi = 1.362 g cm-3, lambda (Cu K alpha) = 1.54178 A, mu (CuK alpha) = 31.5 cm-1, F(000) = 768, T = 163 K, R = 0.032 for 3256 observed reflections. Compound (4): 1,1-dichloro-trans-2-(4-acetoxyphenyl)-3 phenylcyclopropane, C17H14Cl2O2, Mr = 321.2, monoclinic, P2(1)/n, a = 16.555 (4), b = 12.297 (2), c = 7.439 (1) A, beta = 98.31 (2) degrees, V = 1498.5 A3, Z = 4, D chi = 1.423 g cm-3, lambda (Mo K alpha) = 0.71069 A, mu (Mo K alpha) = 3.8 cm 1, F(000) = 664, T = 163 K, R = 0.034 for 2474 observed reflections. The crystal structure determinations show that the relative conformation of the two aryl rings in all four structures are quite similar. In this conformation one of the phenyl rings is in a bisecting position with respect to the cyclopropane ring, while the other is in a perpendicular position. In each of the four molecules the cyclopropane ring shows significant bond-length asymmetry with d[C(2)-C(3)] greater than d [C(1)-C(3)] greater than d[C(1)-C(2)].(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1930833 TI - X-ray analysis of cubic crystals of the complex formed between ribonuclease T1 and guanosine-3',5'-bisphosphate. AB - The complex formed between ribonuclease T1 (RNase T1) and guanosine-3',5' bisphosphate (3',5'-pGp) crystallizes in the cubic space group I23 with alpha = 86.47 (4) A. X-ray data were collected on a four-circle diffractometer to 3.2 A resolution and the structure was determined by molecular-replacement methods [ULTIMA; Rabinovich & Shakked (1984). Acta Cryst. A40, 195-200] based on the RNase T1 coordinates taken from the complex with guanosine-2'-phosphate. Refinement converged at 16.6% for 1540 data with Fo greater than 1 sigma (Fo) with acceptable stereochemistry. The RNase T1 conformation is comparable to that in other complexes which crystallize preferentially in space group P2(1)2(1)2(1) except for side chains that interact intermolecularly. The guanine of 3',5'-pGp is bound to the recognition site in the same way as in other guanine-containing complexes except for its interaction with Glu46. The side-chain carboxylate of this amino acid does not form hydrogen bonds to N1H and N2H of guanine but is rotated so as to permit insertion of two water molecules which replace its acceptor functions. In contrast to other guanosine derivatives which are bound to RNase T1 in the syn form, 3',5'-pGp is anti. This conformation positions the two phosphate groups 'outside' the protein, with hydrogen-bonding contacts only to water molecules; the active site is filled by water. The RNase T1-3',5'-pGp complex probably has biological significance as it may represent the enzyme product complex before dissociation. PMID- 1930834 TI - Solution of the structure of Aspergillus niger acid alpha-amylase by combined molecular replacement and multiple isomorphous replacement methods. AB - The crystal structure of Aspergillus niger acid alpha-amylase was solved by a combination of multiple isomorphous replacement and molecular replacement methods. The atomic coordinates of Aspergillus oryzae (TAKA) alpha-amylase (entry 2TAA in the Protein Data Bank) and experimental diffraction data from a new monoclinic crystal form of TAKA alpha-amylase, were used during the procedure. Sequence identity between the two proteins is approximately 80%. The atomic parameters derived from the molecular replacement solution were too inaccurate to initiate least-squares crystallographic refinement. The molecular model was extensively revised against the experimental electron density map calculated at 3 A resolution. Subsequent crystallographic refinement of this model using synchrotron data to 2.1 A resolution led to a conventional R factor of 16.8%. The structure conforms well to expected stereochemistry with bond lengths deviating from target values by 0.031 A, and planar groups showing a root-mean-square deviation from ideal planes of 0.025 A. PMID- 1930835 TI - Structure and molecular model refinement of Aspergillus oryzae (TAKA) alpha amylase: an application of the simulated-annealing method. AB - Monoclinic crystals of a neutral alpha-amylase from Aspergillus oryzae, containing three molecules in the asymmetric unit, have been reported previously and studied at 3 A resolution [Matsuura, Kunusoki, Harada & Kakudo (1984). J. Biochem. 95, 697-702]. Here we report the solution of the structure of this enzyme in a different crystal form (space group P2(1)2(1)2(1), a = 50.9, b = 67.2, c = 132.7 A), with only one molecule in the asymmetric unit. The structure was solved by the molecular replacement method, using a model of acid alpha amylase from a related fungus A. niger [Brady, Brzozowski, Derewenda, Dodson & Dodson (1991). Acta Cryst. B47, 527-535]. Conventional least-squares crystallographic refinement failed to converge in a satisfactory manner, and the technique of molecular dynamics in the form of the XPLOR package [Brunger (1988). XPLOR Manual. Yale Univ., USA] was used to overcome the problem. A large rigid body type movement of the C-terminal domain was identified and accounted for. The final round of restrained least-squares refinement (at 2.1 A resolution) including 3675 protein atoms and 247 water molecules resulted in a conventional crystallographic R factor of 0.183 and an atomic model which conforms well to standard stereochemical parameters (standard deviation of bond lengths from their expected values is 0.028 A, while that for planar groups is 0.029 A). PMID- 1930836 TI - Use of molecular replacement in the solution of an immunoglobulin Fab fragment structure. AB - Molecular-replacement efficiency depends highly on structural and sequence homologies between available models and the molecule in the crystal being studied. The structure of the Fab fragment of an antibody specific for an influenza virus hemagglutinin was determined by molecular replacement and the Fv and the CH1:CL parts were localized separately. When rotation functions were calculated using known Fv structures as probes, a solution could not be found; this turns out to be due to an insufficient structural homology between the structure and the probes. When the structural homology between the Fv part and its model was enhanced by combining known structures of Fv domains based on sequence information, the right orientation was determined and confirmed by translation-function results. In the cases described here, a high contrast of the translation function was the most reliable criterion to detect a molecular replacement solution. PMID- 1930837 TI - An independent crystallographic refinement of porcine phospholipase A2 at 2.4 A resolution. AB - Porcine phospholipase A2 (Mr = 13,980), trigonal, P3(1)21, a = b = 69.4, c = 70.4 A, one molecule per asymmetric unit, lambda (Cu K alpha) = 1.54 A. Model incorporating 975 protein atoms and eight solvent molecules refined by restrained least-squares fit to a residual R = 0.21 for 6382 reflections from 5 to 2.4 A resolution. PMID- 1930838 TI - Effects of the XR-bonding system on in vitro caries. AB - This study evaluated the effects of a dentin bonding system and glass ionomer liner on in vitro recurrent caries around resin composite restorations in dentin. The dentin adhesive significantly reduced the size of recurrent lesions. The glass ionomer liner, applied either to the axial wall or to the cavosurface margin, provided an even greater cariostatic effect. Both the adhesive and the liner reduced the size of cavity wall lesions. In addition, zones of caries inhibition were present around 75% of restorations lined with glass ionomer cement. PMID- 1930839 TI - Effects of warm air-drying on intra-pulpal temperature. AB - This study was designed to determine what effects different warm air-drying conditions have on the intra-pulpal temperature (IPT), with or without chamber preparation and with or without an acid-etching treatment of the enamel. Four human maxillary centrals and four cuspids had lingual access openings prepared to accommodate a thermal sensor probe. Half of the specimens received a labial chamber preparation and half were acid-etched. All specimens were stored in water at 37 degrees C prior to testing. Labial aspects were positioned at 2 cm and 6 cm from the nozzle of a 500W hair dryer and IPTs were recorded after 15, 30, 45, and 60-second exposures. Exposure times for the acid-etched samples were modified to 10 seconds at 2 cm and 15 seconds at 6 cm. Results showed that for unetched teeth, increases in the IPT were greater at the 2 cm/15-second exposure (a 10.4 12.0 degrees C increase) than at the 6 cm/15-second exposure (a 3.9-6.6 degrees C increase). Even greater temperature changes were seen as the exposure times were increased to 30, 45, and 60 seconds. When the teeth were acid-etched, IPT rises of 5.6-10.1 degrees C and 5.8-8.7 degrees C were measured at 2 cm/10 seconds and at 6 cm/15 seconds, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930840 TI - Effect of a triclosan/copolymer/fluoride dentifrice prophylaxis on the shear bond strength of a composite resin to enamel. AB - A new fluoride dentifrice formulation containing triclosan and a copolymer has been introduced. The purpose of this study was to evaluate the shear bond strength of a resin composite bonded to enamel previously cleaned with this new dentifrice formulation. A total of 45 human extracted permanent molars were used. A flat enamel surface was obtained with 600 grit SiC paper and the teeth randomly distributed into 3 groups of 15 teeth each: Group 1: Pumice prophylaxis with a rubber cup and slow-speed handpiece; Group 2: Prophylaxis with a conventional fluoridated dentifrice (Colgate); Group 3: Prophylaxis with a triclosan/copolymer/NaF dentifrice (Colgate). After prophylaxis, the teeth were acid-etched with a 37% phosphoric acid gel for 30 seconds, rinsed and dried. An unfilled resin (Coe Bond) was thinly applied with a brush and cured for 30 seconds. A nylon ring was placed over the area and filled with a light-cured resin composite (Occlusin). The teeth were thermocycled for 100 cycles, mounted in plastic cups and plaster, and sheared with a knife-edged blade in an Instron running at a crosshead speed of 1 mm/min. The results in MPa were as follows: Group 1: 11.34 +/- 4.57; Group 2: 13.46 +/- 3.60; Group 3: 13.84 +/- 4.33. An ANOVA showed that there was no statistically significant difference among the groups. Fracture within the enamel occurred in 27% in Group 1, 47% in Group 2, and 67% in Group 3. The results support the use of the fluoride dentifrices tested in this study for prophylaxis prior to bonding procedures. PMID- 1930841 TI - Color changes in post-cure heat-treated resin composites. AB - The purpose of this study was to determine the color changes that arise from post cure heat treatment of selected light-cured resin composites by using colorimetric as well as observational methods. Brands of composite were selected that were solely Bis-GMA-based and Bis-GMA/urethane based. These materials also represented a range of filler content (low, medium, and high). The RGB values of cured resin discs were obtained immediately after light-curing as well as after a 5-minute post-cure heat exposure. The range of post-cure temperature was from 100 300 degrees C in 25 degrees C increments. The mean delta L*, delta a*, delta b* and delta E* were determined from red, green and blue data using triplicate replications for each heating condition. Twenty-one observers were asked to determine if the randomly arranged post-cure heated specimens differed in color from the unheated, cured control specimen for each brand. The results indicate that a delta E* value of approximately 3 resulted in greater than 50% of the observers noting a color difference between the post-cure heated specimen and the unheated control. The degree of color change was influenced more by the amount of resin content in the composite systems rather than by the particular resin composition. Microfill resins showed greater potential for color change than did the other types of materials. If clinicians are considering using conventional light-cured composite materials for inlays, the choice of material as well as the post-cure temperature will influence the ability to match the inlay with the original shade of composite selected. PMID- 1930842 TI - Correlation of periodontal probe penetration and degree of inflammation. AB - This histological study correlated the depth of probe penetration to periodontal health in mongrel dogs. Various probing forces were also applied with an electronic pressure-sensitive probe and compared to manual probing. Three adult mongrel dogs with naturally occurring periodontitis in at least one quadrant were selected and gross scaling was only performed in these diseased areas. Mild gingivitis was diagnosed in other areas. One half was scaled and placed on a plaque control regimen to restore clinical health, while the other half remained untreated to maintain the existing gingivitis. The Gingival Index (GI) was recorded on 24 teeth achieving equal representation of different GI values. Probe tips were inserted utilizing manual pressure as well pressures of 15 and 25 gm directed with an electronic pressure-sensitive probe. The probes were bonded to the teeth, and the specimens were sacrificed. Blocks with the probes in place were fixed and decalcified. The probes were removed prior to processing. Sections from each probing site were microscopically analyzed, and the distance was recorded from the tip of the probe to the apical termination of the junctional epithelium (ATJE). The number of inflammatory cells was documented for two fields at x200, one coronal (X) and one apical (Y) to the penetration of the probe's tip. The data were analyzed by two-sample t-test and Pearson product-moment correlation coefficient. A strong correlation was established between probe penetration and degree of inflammation, X (r = 0.6936) and Y (r = 0.7075). The difference in mean inflammation scores between probes coronal or apical to the epithelium was highly significant (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930843 TI - Incorporation of adhesive liners in amalgam: effect on compressive strength and creep. AB - This study evaluated the effects of two adhesive resin liners (Panavia EX and Amalgambond) on the compressive strength and creep rate of a single composition high-copper amalgam alloy (Tytin). Cylindrical specimens were prepared by dead loading or hand-condensing amalgam in a Teflon mold which was unlined, lined with Panavia EX, or lined with Amalgambond. Compressive strength specimens were tested at 1 hour, 24 hours, and 7 days after preparation. Creep specimens were tested at 7 days. The adhesive resin liners did not significantly affect the strength of the Tytin specimens prepared by dead-loading (P greater than 0.05). The Panavia EX significantly reduced the strength of the Tytin specimens prepared by hand condensing (P less than 0.05). The creep rate was not significantly affected by either resin liner. PMID- 1930844 TI - Treatment of "non-restorable" teeth. A case report. AB - The purpose of this article is to present a case report of the dental care for permanent teeth that were originally considered "non-restorable". The temporary placement of stainless steel crowns was completed, followed by traditional endodontic therapy. The crowns were used as build-up matrices, access being prepared in the occlusal of the crown. Glass ionomer silver was then placed, followed by marginal finishing. Although this report is an isolated case, and is considered as temporary treatment, there may be indications to consider this technique for clinical care, on an individual basis. PMID- 1930845 TI - Confocal light microscopic techniques for examining dental operative procedures and dental materials. A status report for the American Journal of Dentistry. AB - A new form of light microscopy is compared with the current microscopic techniques for examining restorative dental procedures and dental materials. Confocal microscopy enables thin optical sections to be made below the surface of semi-transparent specimens with improved resolution. This paper reviews the different types of confocal microscopes, identifying the strengths and weaknesses of the various instruments. It also reviews some of the techniques for specimen preparation and the control of factors influencing image quality. PMID- 1930846 TI - Altered coriolis stress susceptibility in essential hypertension. AB - Patients with hypertension frequently have vague complaints of dizziness and many other symptoms experienced by healthy individuals with motion sickness. We examined vestibular function in patients with essential hypertension, and we determined whether patients with essential hypertension are more prone to motion sickness using Coriolis stress testing. Vestibular function and Coriolis stress susceptibility were measured in 12 normotensive (NT) and seven asymptomatic patients with mild essential hypertension (HT). The Coriolis stress susceptibility index (CSSI) was calculated from the number of head movements in the four cardinal directions an individual could complete while being rotated in a computerized chair at increasing velocity before they developed motion sickness. The patients with hypertension had normal vestibular function and normal vestibuloocular responses as measured by standard techniques. Subjects with hypertension had significantly decreased Coriolis stress susceptibility scores compared to normotensive subjects (NT, 29.70 +/- 4.8; v HT, 5.48 +/- 2.0, P less than .001) and significantly decreased suppression of postrotatory nystagmus (NT, 44.5% +/- 3.8; v HT, 19.1% +/- 6.9, P less than .05). Medical treatment of hypertension did not result in an increased tolerance to provocative stimuli for motion sickness. It is suggested from our data that an increased susceptibility to motion sickness and abnormal vestibular responses to normal motion may account for many of the vague symptoms of "dizziness" reported by a large number of hypertensive patients. PMID- 1930848 TI - Possible role of prostacyclin synthase in altered prostacyclin generation in DOCA salt hypertensive rats. AB - Prostacyclin (PGI2) synthase is one of the key enzymes for vasodepressor PGI2 biosynthesis in the vascular wall. In this study, we attempted to define the alterations in PGI2 synthase and its role in the PGI2 generation in the vascular wall of deoxycorticosterone acetate (DOCA)-salt rats. The PGI2-generating capacity was enhanced significantly when DOCA-salt rats established hypertension, whereas the generation of other arachidonate metabolites, eg, PGE2, PGF2 alpha, and thromboxane, was unaltered. Moreover, the increase in PGI2 generation was associated with an increase in PGI2 synthase activity in the vascular wall. Indeed, the averaged PGI2 generating capacity was closely correlated to the averaged PGI2 synthase activity in DOCA-salt hypertensive rats and three lines of control rats. Incontrast, phospholipase C and phospholipase A2, both of which liberate arachidonate for PGI2 synthesis, were rather lowered in DOCA-salt hypertensive rats. These data clearly indicate that vascular PGI2 generation is increased in the development of DOCA-salt hypertension and that PGI2 synthase is mainly responsible for this enhancement. The increased PGI2 synthase may be relevant to the blood pressure elevation and is expected to have beneficial effects on the vascular protection in hypertension. PMID- 1930849 TI - Blood pressure response during long-term treatment with magnesium is dependent on magnesium status. A double-blind, placebo-controlled study in essential hypertension and in subjects with high-normal blood pressure. AB - Both experimental and epidemiological studies support the idea of magnesium supplementation in essential hypertension. We added 15 mmol Mg to a free diet in 71 subjects with mild essential hypertension or a high-normal blood pressure in a double-blind, placebo-controlled study over 6 months. The treatment, which raised urinary magnesium excretion 30%, induced no general effects on the blood pressure. However, when the changes in blood pressure in the actively treated group were related to the pretreatment magnesium status, a correlation was found between pretreatment urinary magnesium excretion and the induced change in supine blood pressure (P less than .05) with a blood pressure reduction in subjects with a low pretreatment urinary excretion of magnesium, and a pressor effect in the subjects with the highest pretreatment levels of urinary magnesium. The induced change in blood pressure was furthermore found to be inversely correlated to the changes in serum magnesium and urinary excretion of sodium (P less than .03) induced by treatment indicating that both a direct calcium antagonist action of magnesium at the cellular level as well as a diuretic effect of the increased magnesium load might be involved in the blood pressure effects of magnesium. Pretreatment serum potassium concentration also appeared to be a predictor of the induced change in standing blood pressure (P less than .03). In conclusion, magnesium supplementation does not seem to be effective in unselected mild hypertensive subjects or in subjects with a high-normal blood pressure and can therefore not be generally recommended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930850 TI - Therapeutic benefit of captopril in salt-loaded stroke-prone spontaneously hypertensive rats is independent of hypotensive effect. AB - In the present study we examined whether the angiotensin I converting enzyme inhibitor, captopril, would protect stroke-prone spontaneously hypertensive rats (SHRSP) from stroke and renal pathology over a 26-week period. In the control group of six untreated SHRSP fed Stroke-Prone Rodent Diet and 1% NaCl drinking solution, all animals developed severe hypertension and stroke by 16.1 weeks of age. In eight salt-loaded SHRSP treated with oral captopril (50 mg/kg/day) beginning at 8.4 weeks of age, systolic blood pressure was slightly but temporarily suppressed and then continued to rise; by 12 weeks of age systolic blood pressure reached levels of severe hypertension, 240 +/- 8 mm Hg, and did not differ from that of untreated SHRSP. No deaths or brain lesions were noted in captopril-treated SHRSP despite severe hypertension maintained through 26 weeks of age when the study ended. Captopril treatment prevented increases in urinary protein excretion (14 +/- 2 v 63 +/- 16 mg/day at 11.7 weeks of age, P less than .01) and the severe brain, renal, and cardiac vascular lesions observed in untreated SHRSP. When maintained on Stroke-Prone Rodent Diet and saline, plasma renin activity of untreated SHRSP surviving until 14.5 weeks of age was markedly increased (29.1 +/- 9.4 ng Ang I/mL/h) compared with either untreated SHRSP (9.2 +/- 2.5 ng Ang I/mL/h, P less than .01) or Wistar-Kyoto rats (3.5 +/- 1.0 ng Ang I/mL/h, P less than .01) maintained on standard diet and water.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930847 TI - Hyperactivation of phospholipase C does not support the enhanced proliferation of aortic smooth muscle cells from spontaneously hypertensive rats. AB - When cultured in the presence of fetal calf serum, arterial smooth muscle cells from spontaneously hypertensive rats (SHR) proliferate more rapidly and are more numerous at confluency than cells from normotensive Wistar-Kyoto (WKY) animals. The phenomenon has been demonstrated in several laboratories but its molecular origin remains unclear. On the other hand phospholipase C activation and c-fos transcription are early events able to trigger cell mitosis. Therefore, the enhancement of inositol phosphates formation induced in SHR cells by various vasoactive agents and growth factors suggests that this enzyme might be implicated in the abnormal proliferation triggered by serum. In this case a unique molecular abnormality would be responsible for both arterial hypercontractility and dystrophy encountered in hypertension. In order to test this hypothesis we have compared DNA replication, phospholipase C activation, and c-jun and c-fos nuclear protooncogene transcriptions stimulated by fetal calf serum (FCS), vasoactive agents (angiotensin II and vasopressin), and epithelial growth factor (EGF) in SHR and WKY rat cells. The results obtained with these various agonists tested under the same experimental conditions confirm that the classical pathogenic diagram: (PLC hyperactivation----increase in c-fos transcription----enhanced cell proliferation) may apply to the action of vasoactive agents which are only slightly mitogenic on SHR cells, but not to the very important effect of fetal calf serum. Indeed, FCS stimulated inositol phosphate formation and c-jun and c-fos transcription, but none of these parameters was enhanced in SHR cells. Phospholipase C activation may exert some control upon DNA replication, as its partial inhibition by pertussis toxin coincided with an equivalent decrease in thymidine incorporation. It is, however, not absolutely required for the onset of DNA replication in aortic smooth muscle cells, as shown by the results obtained with EGF under the same experimental conditions. An abnormal molecular reaction different from PLC activation is therefore responsible for the enhanced proliferation of cultured SHR aortic smooth muscle cells, and several cell alterations may concur to the formation of the hypertensive arteriopathy. PMID- 1930851 TI - Carotid sinus compliance and baroreflex responses in hypertensive dogs. AB - The hypothesis that changes in baroreflex function seen in hypertension could be explained by a decreased vascular compliance in the carotid sinus region itself was tested. Six dogs were made chronically hypertensive (MAP = 146.0 +/- 3.3 mm Hg) using a bilateral renal wrap technique, while six other dogs were sham operated and served as normotensive controls (MAP = 125.8 +/- 4.7 mm Hg). Six weeks after the procedure, compliance of the carotid sinus region was measured, and carotid baroreflex control of arterial pressure and heart rate was assessed acutely. Dogs were anesthetized with sodium pentobarbital and the carotid sinus was isolated and perfused at controlled pressures. Vagotomy was performed to eliminate aortic and cardiopulmonary reflex buffering. The carotid sinus pressure (CSP) was changed from 25 to 250 mm Hg in a stepwise fashion, and the corresponding arterial pressure, heart rate and volume changes were recorded. Compliance was determined as the change in volume infused divided by the changes in pressure achieved. Significant differences between the normotensive and hypertensive groups were found in the reflex responses of arterial pressure and heart rate to changes in CSP. Carotid sinus compliance decreased with increasing CSP, but was not different in the two groups. Changes in baroreflex responses seen in mild hypertension occur without significant changes in carotid sinus compliance, and cannot be explained solely by a decreased compliance in the receptor wall. PMID- 1930852 TI - A new diagnostic test for primary aldosteronism. AB - Isotonic-isooncotic central volume expansion by head-out water immersion was induced in six aldosterone-producing adenoma subjects and in six patients with idiopathic hyperaldosteronism. Plasma renin activity and plasma aldosterone levels did not significantly change during water immersion while serum cortisol was significantly suppressed (P less than .001) and the aldosterone-cortisol ratio increased (P less than .02) in aldosterone-producing adenoma patients. Water immersion also revealed the failure of plasma aldosterone levels to decrease below 10 ng/dL in these subjects, thus confirming previous results obtained during isotonic saline infusion. Otherwise, plasma renin activity and plasma aldosterone were significantly reduced (P less than .05 and P less than .01 respectively) by water immersion and plasma aldosterone invariably fell below 10 ng/dL in patients with idiopathic aldosteronism. In view of the diagnostic reliability of such a suppression test we conclude that water immersion is suitable for discriminating between the two forms of primary aldosteronism. We therefore suggest its use for assessing renin-aldosterone responsiveness in primary aldosteronism. PMID- 1930853 TI - Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia. AB - The pregnancy disorder preeclampsia continues as a major cause of maternal and infant mortality and morbidity. Despite intensive research since its recognition 100 years ago, our lack of understanding is evidenced by therapy which remains empiric, early delivery. Part of our failure to more completely understand the syndrome is due to excessive attention to the blood pressure elevation which accompanies the disorder, to the exclusion of a panoply of other physiologic aberrations. Although hypertension, if markedly elevated, can lead to maternal morbidity, it is not usually an important contributor to the pathophysiology of preeclampsia. It is primarily important as a marker for vasoconstriction, which in association with activation of coagulation reduces perfusion to many organs, including the fetal-placental unit. The earliest and likely most important pathophysiologic change is reduced placental perfusion secondary to abnormal implantation and/or a relative increase in placental mass. We propose that reduced placental perfusion results in the production of agent(s) by this organ, which injures or activates endothelial cells. The resulting endothelial cell dysfunction increases sensitivity to normal endogenous pressors, activates the coagulation cascade, and increases vascular permeability. These changes produce the characteristic pathophysiologic changes of the disorder. Evidence supporting this hypothesis includes abnormal endothelial morphology long recognized in glomerular capillaries, increased circulating fibronectin, and increased plasma mitogenic activity that long antedates the clinical disorder. In addition, an agent(s) is present in the blood of these women which activates endothelial cells in vitro as evidenced by increased release of [51Cr] chromium and increased production of PDGF. Preeclampsia is clearly more than "pregnancy induced hypertension." PMID- 1930854 TI - Elevated levels of parathyroid hormone in essential hypertensive patients with increased erythrocyte potassium efflux. AB - Previous observations suggest that Ca(2+)-dependent K+ efflux is increased in erythrocytes from spontaneously hypertensive rats. On the other hand, it has been reported that hyperparathyroidism induces an increase in Ca(2+)-dependent K+ efflux of human erythrocytes. To investigate whether Ca(2+)-dependent K+ efflux is altered in essential hypertension quinine-sensitive K+ efflux was measured in erythrocytes from 20 normotensive controls and 30 nontreated essential hypertensives. The quinine-sensitive K+ efflux was similar for hypertensive patients (593 +/- 20 mmol/L cells/h) as compared with normotensive controls (532 +/- 34 mmol/L cells/h). Ten hypertensives exhibited values of quinine-sensitive K+ efflux above an upper normal limit of 650 mmol/L cells/h. As compared with controls those patients presented elevated plasma levels of parathyroid hormone (P less than .05). In addition, a positive correlation was found between parathyroid hormone and quinine-sensitive K+ efflux in the above ten hypertensives (R = 0.85, P less than .001). These results suggest that an excess of parathyroid hormone may be involved in the increase of Ca(2+)-dependent K+ efflux present in some essential hypertensive patients. PMID- 1930855 TI - Effects of calcium channel blockade on the hemodynamic responses to endothelin infusion in conscious sheep. AB - The hemodynamic responses to bolus injection of endothelin I (ET) at 5, 15, and 50 micrograms were examined in conscious sheep (n = 5) before and after infusion of nisoldipine at 25 micrograms/kg/h. Endothelin produced dose-dependent increases in mean arterial pressure (MAP + 87 +/- 6 mm Hg at 50 micrograms) and calculated total peripheral resistance (CTPR + 54 +/- 15 mm Hg/L/min at 50 micrograms) and decreases in heart rate (HR - 34 +/- 6 beats/min at 50 micrograms) and cardiac output (CO - 2.6 +/- 0.3 L/min at 50 micrograms) but no change in stroke volume (SV). Nisoldipine attenuated (P less than .05) the endothelin-induced changes in MAP (+26 +/- 3 mm Hg at 5 micrograms) and CTPR (+13.0 +/- 2.1 mm Hg/L/min at 50 micrograms), but not the fall in heart rate or cardiac output. These data are compatible with the hypothesis that vasoconstrictor effects of ET in sheep are in part dependent on influx of calcium through L-type channels. PMID- 1930856 TI - British MRC trial of treatment for mild hypertension--a more favorable interpretation. PMID- 1930857 TI - Heritability estimate of erythrocyte Na-K-Cl cotransport in normotensive and hypertensive families. AB - Na-K-Cl cotransport was measured in 209 essential hypertensive patients (EH) and in 114 normotensive controls (NT). The distribution of Na-K-Cl cotransport was bimodal in EH and unimodal in NT. The EH with higher Na-K-Cl cotransport values had increased passive permeability to Na in fresh erythrocytes and increased Li Na countertransport compared to NT. Li-Na countertransport was significantly increased in the EH as a whole, but the increase was accounted for by some EH individuals with elevated Na-K-Cl cotransport values. A simple biometric analysis of the Na-K-Cl cotransport was performed for 287 individuals of 86 families with different prevalence of hypertension (neither parent hypertensive, 39 families; one, 31 families; or both, 16 families). Na-K-Cl cotransport was not correlated between spouses, but was correlated highly significantly between the average value of the two parents (mid-parent) and offspring. The polygenic additive heritability (h2) was about 50% for all families considered together. It increased slightly for the hypertensive families analyzed alone (no significant correlation was found, and hence genetic heritability, in the normotensive families). Finally, after applying arbitrary cut-off points to the Na-K-Cl cotransport values, segregation analysis showed that some major gene, recessive for the high allele, also contributes to the phenotypic value of Na-K-Cl cotransport. PMID- 1930858 TI - Plasma renin activity and norepinephrine as predictors for antihypertensive effects of nifedipine and captopril. AB - To examine predictors for the efficacy of antihypertensive agents, we investigated the effects of nifedipine and captopril on blood pressure (BP) and humoral factors in patients with essential hypertension. Eleven essential hypertensive patients (mean age: 54) were treated with long acting nifedipine at 20 to 40 mg/day for 8 weeks and 25 essential hypertensives (mean age: 51) were treated with captopril at 37.5 to 75 mg/day. Blood pressure was measured every 2 weeks. Plasma renin activity (PRA), and plasma concentrations of aldosterone, epinephrine and norepinephrine were determined before and at the end of treatment. Both nifedipine and captopril decreased BP (nifedipine: mean BP 119 +/ 3 to 101 +/- 2 mm Hg, captopril: 124 +/- 2 to 100 +/- 2, P less than .01 for each), whereas neither of them affected heart rate. The 8-week treatment of nifedipine showed no significant effect on humoral factors. Captopril increased PRA by 63% (P less than .05) and decreased plasma epinephrine by 42% (P less than .01) and norepinephrine by 35% (P less than .01). The change in mean BP was positively correlated with pretreatment PRA (r = 0.68, P less than .01) in nifedipine-treated patients and inversely with pretreatment norepinephrine (r = 0.53, P less than .01) in captopril treatment. The results suggest that both nifedipine and captopril were effective antihypertensive agents and that the long term treatment of nifedipine is more effective in essential hypertensives with lower PRA, while captopril is more effective in those with higher plasma norepinephrine concentration. PMID- 1930859 TI - Long-term effect of nifedipine and hydrochlorothiazide on blood pressure and sodium homeostasis at varying levels of salt intake in mildly hypertensive patients. AB - To elucidate and compare the effects of nifedipine (NIF) and hydrochlorothiazide (HCTZ) on blood pressure (BP) and sodium (Na) balance, we conducted a randomized, double-blind, crossover study with 50 mg/day HCTZ and 90 mg/day NIF (as the sustained-release gastrointestinal therapeutic system preparation) in 10 mildly hypertensive patients over approximately 8 weeks. Prior to treatment, the subjects were brought into balance at an intake of 150 mmol/day. During treatment, Na intake was lowered and raised to 50 and 300 mmol/day, respectively, in random order. Then, the subjects were brought into balance on treatment at a level of 150 mmol/day. Balance observations were made during and after the drugs were discontinued. Both HCTZ and NIF lowered BP similarly. When Na intake was lowered from 150 to 50 mmol/day, a significant decrease in diastolic BP was observed with HCTZ. Increasing Na intake to 300 mmol/day did not affect BP. At an intake of 150 mmol/day, HCTZ caused prompt natriuresis, with a negative balance of 150 mmol by 3 days. No initial natriuresis could be shown with NIF. Decreasing Na intake to 50 mmol/day caused prompt negative Na balance with both drugs; increasing it to 300 mmol/day was associated with +150 mmol Na balance with HCTZ while no significant increase was seen with NIF. Discontinuing both drugs caused prompt increase in BP and Na retention over 6 days, which was not different for the drugs. Plasma renin activity (PRA) increased with HCTZ but not with NIF. Further, changing Na intake affected PRA with HCTZ. With NIF, PRA appeared to be uncoupled from the effects of dietary Na intake. In contrast to HCTZ, no adverse metabolic effects were observed with NIF. The data suggest that NIF results in chronic mild natriuresis similar in magnitude to HCTZ. The PRA appears inactivated, although not lowered. The effects of NIF on BP may be at least in part related to the natriuresis and blunting of PRA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930860 TI - Aspirin test for differentiation of unilateral renovascular hypertension from hyperreninemic essential hypertension. AB - Responses of renin release and blood pressure to aspirin DL-lysine (ASP) were examined to find out if the responses could help in the differentiation between unilateral renovascular hypertension (RVH) and hyperreninemic essential hypertension (EHT). The two studies involved ten patients with unilateral RVH, eight with hyperreninemic EHT, and five with hyporeninemic EHT. In a radiological study, before and 30 min after an intravenous injection of ASP (18 mg/kg), renal venous and abdominal aortic plasma was sampled and assayed for prostaglandin (PG) E2 and plasma renin activity (PRA). Systemic blood pressure was measured serially. The reproducibility of the responses to ASP was confirmed in a bedside study. In unilateral RVH, ASP suppressed renin release from the stenotic kidney and reduced the renal vein PRA ratio to less than 1.5 via the inhibition of PG synthesis, which is accelerated in that kidney. The mean suppression of aortic PRA at this dose of ASP was 35% in these patients, and their blood pressure decreased in proportion to the suppression of PRA. However, in the two EHT groups, ASP elevated the mean blood pressure. The renal synthesis of PGE2 was inhibited by ASP in all patients, but the suppression of PRA, while small, was significant (19% in the aorta) in the patients with hyperreninemic EHT, and not significant in patients with hyporeninemic EHT. The different responses of blood pressure and PRA to ASP between RVH and EHT were reproducible in the bedside study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930862 TI - Reassessment of the predictive value of the postural stimulation test in primary aldosteronism. AB - Postural stimulation tests (PST) from 146 patients with primary aldosteronism were reviewed: 83 had an aldosterone-producing adenoma (APA), 48 idiopathic hyperaldosteronism (IHA), nine primary adrenal hyperplasia (PAH), and six aldosterone-producing renin-responsive adenoma (AP-RA). Plasma aldosterone and cortisol levels were measured after overnight recumbency and in response to upright posture for 2 to 4 h. The test was considered invalid in 32% of the patients because cortisol levels increased during the maneuver. As both cortisol and aldosterone are responsive to ACTH in subjects with primary aldosteronism, as well as in normal subjects, we examined their percent variation instead of the absolute values. In order to validate those tests in which cortisol increased, we subtracted the percent cortisol change from the percent aldosterone response. An aldosterone increase of less than 30% (considered a positive response for the presence of an adenoma) identified 76 of the 89 patients with an adenoma (APA and AP-RA) (sensitivity of 85%). Among the 13 false-negative tests, six were proven cases of AP-RA. In each and every case an adenoma was detected by CT/MRI scanning (or bilateral adrenal vein catheterization). Hypertension was ameliorated or cured by surgery. A postural response of less than 30% was also present in 11 of the 57 patients who did not have a discrete adenoma confirmed by imaging techniques (specificity of 81%). Among these false-positive results there were the nine cases of PAH where the hypertension could be ameliorated or cured by partial removal of hyperplastic adrenal tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930861 TI - Abnormalities of insulin and lipid metabolism in Milan hypertensive rats. AB - Plasma glucose, insulin, triglyceride, and cholesterol concentrations were measured in male rats of the Milan hypertensive strain (MHS) and compared to the Milan normotensive strain (MNS) of the same body weight. Both blood pressure (P less than .001) and left ventricular weight (P less than .005) were higher in rats of the MHS. Although plasma glucose concentrations were similar in both groups, mean (+/- SEM) plasma insulin concentration were significantly higher (P less than .01) in MHS as compared to MNS rats (30 +/- 4 v. 13 +/- 5 microU/mL). In addition mean (+/- SEM) plasma triglyceride concentrations were higher (P less than .01) in MHS rats (112 +/- 9 mg/dL) than in MNS rats (81 +/- 6 mg/dL), as were plasma cholesterol concentrations (114 +/- 3 v 100 +/- 2 mg/dL, P less than .001). These data demonstrate the presence of hyperinsulinemia and hypertriglyceridemia in another genetic model of rat hypertension. PMID- 1930863 TI - Hypertension and ischemic heart disease in Australian aborigines. PMID- 1930864 TI - Incidence of stroke and acute myocardial infarction in subtropical islands, Okinawa, Japan. PMID- 1930866 TI - Identification of pathogens in the condensates from air pressure systems in dental offices. AB - We examined the air pressure systems in 23 dental offices and found growth of Group A Streptococci and/or Staphylococcus Aureus in 91 percent of them. We also examined nine handpiece lines from these 23 offices and found growth of pathogens in 78 percent of them. Correlation of the growth found in the handpiece lines and the growth found in the air pressure tanks needs further study to determine if an interrelationship exists between these two areas of contamination. However, contamination does exist in both areas and these areas deliver contaminated air under pressure to the oral environment. We need to consider mechanisms for filter entrapment or sterilization of these pathogens. PMID- 1930865 TI - OSHA clarifies infection control policy. PMID- 1930867 TI - The risk of AIDS to the dental professional. PMID- 1930868 TI - Exodontia simplified: an interview with Matthias Hourigan, DDS. Part one. Interview by Dr. Hugh F. Doherty, CFP. PMID- 1930869 TI - AACD survey finds bleaching safe and effective. PMID- 1930870 TI - Overcoming the complexity of impression materials: Part I. An interview with Alan Boghosian, DDS. PMID- 1930871 TI - Osseointegrated dental implants: a unique application. PMID- 1930872 TI - The insurance game: emergency treatment and oral surgery. PMID- 1930873 TI - Cosmetic correction of crowded anterior teeth. PMID- 1930874 TI - Electrotherapeutics in managing TMD. PMID- 1930875 TI - BMY 21502 and piracetam facilitate performance of two-choice win-stay water escape in normal rats. AB - Sprague-Dawley rats given either 5 or 10 mg/kg of a new compound, BMY 21502, 150 mg/kg of piracetam or a dose of methylcellulose vehicle (p.o.) daily for 38 days beginning two days before training were compared on performance of a win-stay water-escape task in a circular water maze requiring the use of working memory. The task involved giving the rats pairs of trials in which the location of a submerged escape platform remained the same within a pair of trials but changed semirandomly across pairs. Rats receiving either 5 mg/kg BMY 21502 or piracetam made more correct choices than did rats receiving only the vehicle (p less than 0.05 in each case). The facilitated performance was associated with making fewer perseverative responses that resulted in errors. PMID- 1930876 TI - A comparison between the non-competitive NMDA antagonist dizocilpine (MK-801) and the competitive NMDA antagonist D-CPPene with regard to dopamine turnover and locomotor-stimulatory properties in mice. AB - Following intraperitoneal administration of the non-competitive N-methyl-D aspartate (NMDA) antagonist dizocilpine (MK-801), levels of the dopamine (DA) metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased in mouse striatum and limbic forebrain. When dizocilpine was given to animals treated with NSD 1015, an inhibitor of 3,4-dihydroxyphenylalanine (DOPA) decarboxylase and monoamine oxidase, there was an increase in levels of DOPA and 3-methoxytyramine (3-MT). These findings suggest that dizocilpine stimulates DA synthesis and release in mouse brain. Following dizocilpine treatment a clear-cut increase in spontaneous locomotor activity was observed, probably partly due to enhanced dopaminergic tone. The competitive NMDA antagonist D-CPPene produced locomotor stimulation as well, but in contrast to following dizocilpine treatment levels of 3-MT decreased. Thus the stimulation of locomotor activity following D CPPene treatment does not seem to be mediated through activation of central dopaminergic systems. However, haloperidol pretreatment antagonized this locomotor response, indicating that the dopaminergic system plays a permissive role in this context. PMID- 1930877 TI - The effect of long-term treatment with deprenyl on basal and L-dopa evoked dopamine release in vitro from the corpus striatum of aged rats. AB - In the present experiment, male rats (15-17 months) were injected with deprenyl (0.25 mg/kg) three times per week for six months. At 21-23 months of age the male rats were sacrificed, the corpus striatum removed and superfused in vitro. Basal and evoked dopamine and DOPAC levels, as obtained with either two infusions of L dopa (L-dopa/L-dopa) or L-dopa followed by amphetamine (L-dopa/AMPH), were measured from effluent superfusion samples and compared with values obtained from similarly aged animals treated identically with saline and from that obtained with young (2-4 months) animals. Treatment with deprenyl resulted in significantly greater basal dopamine and significantly lower basal DOPAC output compared with basal release levels from saline-treated aged rats and young animals. Responses to L-dopa/L-dopa or L-dopa/AMPH evoked dopamine and DOPAC release did not differ between deprenyl and saline-treated aged rats, however, both groups showed a significantly reduced response profile to these stimulations (L-dopa/L-dopa or L-dopa/AMPH) compared to that of young rats. These results indicate that the selective Type-B monoamine oxidase inhibitor, deprenyl, exerts a basic change in dopamine metabolism within the corpus striatum of aged rats resulting in an increase of endogenous dopamine and a decrease in endogenous DOPAC output. PMID- 1930878 TI - Stereospecificity of the dopamine receptor mediating the growth hormone response to apomorphine in man. Short communication. AB - The stereospecificity of the D-2 receptor mediating the growth hormone (GH) response to apomorphine (Apo) and the D-2 receptor regulating prolactin (PRL) secretion were investigated in 10 normal men by examining the effects of cis flupenthixol (cis-Fx) and trans-flupenthixol (trans-Fx). cis-Fx (1 mg six hourly times four doses) antagonized the GH response to Apo HCl (0.5 mg sc) and increased basal serum PRL concentrations whereas the trans-isomer showed no effect. These findings (a) provide further evidence that the GH response to Apo is mediated by stimulating dopamine (DA) receptors, and, (b) demonstrate stereospecificity of the DA receptor mediating the GH response to Apo and the DA receptor regulating PRL secretion. PMID- 1930879 TI - Reinnervation of the transplanted vas deferens: differential recovery of various biochemical and pharmacological parameters. AB - Biochemical and pharmacological parameters were used to follow the innervation characteristics of the rat was deferens transplanted (T) to the caecum. After about 5 months, a regeneration of autonomic nerves was clearly shown: first, by a complete recovery of neuronal uptake, indicated by: a) potentiation by cocaine of epinephrine (EPI) dose-response curves (T = 1.47 +/- 0.25, controls (C) = 1.50 +/ 0.14 log units); b) reversion to normal levels of pD2 values for norepinephrine (NE) and EPI (T = 6.6 +/- 0.1; 7.0 +/- 0.1, and C = 6.4 +/- 0.1; 6.9 +/- 0.1, respectively); second, a partial restoration of nerve terminals, and corresponding pools of NE, which was seen through histofluorescence and was indicated by a percent increase of: a) NE content, 47% (T = 3.8 +/- 0.8, C = 8.5 +/- 0.7 micrograms/g); b) dopamine-beta-hydroxylase (DBH) activity, 37% (T = 136 +/- 80, C = 364 +/- 15 nmol(hr.g); c) release of NE by 57 mM-potassium, 23% (T = 33.0 +/- 12.0, C = 147 +/- 14 ng/g. 5 min). Yet, two peculiarities of denervated organs remained practically unchanged even after 5-month transplantation: NE supersensitivity, measured by the relative responsiveness (rho) ratio (T = 0.96 +/- 0.02, C = 0.69 +/- 0.03), and tyramine-induced contraction, that was recovered by only 14% (T = 10.0 +/- 2.4, C = 72.0 +/- 3.5 mm). This differential recovery of the aforementioned parameters is discussed in the light of receptor mechanisms and functional changes following reinnervation. PMID- 1930880 TI - Antidepressant drugs increase the locomotor hyperactivity induced by MK-801 in rats. AB - MK-801, a non-competitive NMDA receptor antagonist, induced the locomotor hyperactivity in rats. Imipramine (IMI), amitriptyline (AMI), citalopram (CIT) given acutely increased the MK-801-induced locomotor hyperactivity. Mianserin (MIA) showed a similar but weaker effect. Haloperidol completely blocked the hyperactivity induced by the antidepressant drug (AD) + MK-801. Prazosin had an only weak antagonistic effect. Repeated treatment with AD increased the MK-801 locomotor hyperactivity to a greater extent than acute treatment. This effect was completely blocked by haloperidol and only partly by prazosin. The obtained results indicate that the dopamine system may be involved, at least in part, in the potentiating effect of the combined treatment with AD + MK-801. PMID- 1930881 TI - Coexisting dysregulations of both the sympathoadrenal system and hypothalamic pituitary-adrenal-axis in melancholia. AB - In order to delineate putatively coexisting dysregulations between sympathoadrenal system and hypothalamic-pituitary-adrenal (HPA)-axis during depression, the authors measured the following: the pre and postdexamethasone (1 mg) 24 hr urine excretion of noradrenaline, dopamine, adrenaline, 3-methoxy-4 hydroxyphenylglycol (MHPG), free cortisol (UFC), and plasma cortisol. Melancholic patients were characterized by a significantly higher excretion of noradrenaline, dopamine and adrenaline, combined with significantly increased UFC, postdexamethasone plasma cortisol, and UFC values. We found significant and positive correlations between UFC on the one hand, and the 24hr urine excretion of noradrenaline, dopamine, and adrenaline, on the other. By the same token, we established significant relationships between the 24 hr urine excretion of those catecholamines and the postdexamethasone UFC and plasma cortisol values. Cortisol nonsuppressors exhibited a significantly higher excretion of noradrenaline, dopamine and adrenaline, as compared with cortisol suppressors. Dexamethasone administration did not have a significant effect on the urinary output of noradrenaline, dopamine, adrenaline or MHPG. PMID- 1930883 TI - Protein digestibility: in vitro methods of assessment. PMID- 1930882 TI - Time-dependency for the bimodal effect of melatonin on calcium uptake in rat hypothalamus. Short communication. AB - The activity of 0.01-1 microM of melatonin on depolarization-induced 45Ca2+ influx by hypothalamic synaptosomes of rats killed at late evening (2000 h) depended on melatonin preincubation time, exhibiting an early (10 min) stimulation of uptake and an inhibition after 30 min of incubation. Both stimulatory and inhibitory effects were maximal at 2000 h and tended to a minimum at 2400 h, exhibiting intermediate values at 400 h. At 1000 h, only inhibitory effects of melatonin (1 microM) on Ca2+ uptake were found. PMID- 1930884 TI - Protein and enzyme stability: structural, thermodynamic, and experimental aspects. PMID- 1930885 TI - [Evaluation of intraoperative transesophageal echocardiography]. AB - With the development of medical ultrasonics, anesthesiologists have recognized the usefulness of transesophageal echocardiography as an intraoperative monitoring. Intraoperative transesophageal echocardiography is now used to monitor left ventricular function and to confirm the result of surgical correction immediately after cardiac operation. In this study, we evaluated the detectability of air embolism and the effect of hemodynamic changes on physiological mitral regurgitant flow by transesophageal Doppler echocardiography (TEDE). TEDE was more sensitive than precordial Doppler ultrasound in detecting intracardiac air. TEDE could detect air inflow to the right atrium earlier than alterations in pulmonary hemodynamics. The monitoring of intracardiac air by TEDE minimized the complication by air embolism. Regarding physiological mitral regurgitation, the degree of regurgitation increased with the elevation of BP in 70% of patients. An increase in afterload seemed to cause accidental volume loading on the left heart resulting in physiological mitral regurgitation. Intraoperative monitoring of regurgitant flow by TEDE was useful for the anesthesiologist as a guide of hemodynamic management. Transesophageal echocardiography is a useful intraoperative monitoring method regardless of its several disadvantages. With further improvement of mechanical device, transesophageal echocardiography will be more often and safely performed in operating room. PMID- 1930886 TI - [Efficacy of transesophageal echocardiography immediately after open heart surgery: diagnosis of coagula tamponade]. AB - Massive pericardial coagula were detected by transesophageal echocardiography in some patients with low cardiac output failure immediately after open heart surgery. Characteristically, the coagula were localized anterior to the right atrium and right ventricle in all patients. The coagula could not be detected by transthoracic echocardiography. Despite of low output, absence of wall motion abnormality of the left ventricle, tachycardia, elevated atrial pressure and small left ventricular cavity lead to diagnose cardiac tamponade by pericardial coagula. Neither the right atrial nor the right ventricular wall showed collapsing motion except the area with pericardial effusion. Massive coagula in the anterior mediastinum produced similar clinical manifestation, but could be differentiated from pericardial coagula by echographic identification of the anterior pericardium. Pericardial coagula were also observed in patients with superior vena cava syndrome, but low right atrial pressure differentiated it from coagula tamponade. In all of the present patients, usual transthoracic echocardiography did not offer any sufficient images for diagnosing pericardial coagula. Transesophageal echocardiography was indispensable for detecting pericardial coagula soon after open heart surgery. PMID- 1930887 TI - [Imaging of coronary arteries and measurement of coronary flow using transesophageal Doppler echocardiography: a comparison with transthoracic Doppler echocardiography]. AB - Recent advances in Doppler echocardiographic techniques, especially using transesophageal approach, enable us to observe coronary arteries and their blood flow. However, the advantages of transesophageal approach in the evaluation of coronary artery are indistinct. The aim of this study was to examine the ability of transesophageal Doppler echocardiography (TED) and transthoracic Doppler echocardiography (TTD) to visualize coronary artery and measure its flow. The study population consisted of 17 healthy subjects and 41 patients with heart diseases (arrhythmia in 2, valvular disease in 10, ischemic heart disease without complete or subtotal obstruction of coronary artery in 22, congenital heart disease in two, cardiomyopathy in four, and infective endocarditis in one). Thirty subjects were examined by TED, and 44 subjects were examined by TTD. Two patients with complete obstruction of the proximal right coronary artery (RCA), who were not included in the above-mentioned subjects, were examined by TED. The results were as follows: 1) The detection rate of coronary arteries by TED and TTD were: left main trunk (LMT); 96.7/86.4%, left anterior descending artery (LAD) and left circumflex artery (LCx); 83.3/56.8%, and RCA; 63.3/38.6%, respectively. 2) Visible length from the orifice: LMT to LAD; 22.2/30.8 mm, RCA; 20.4/22.3 mm. 3) The detection rate of coronary flow by pulsed Doppler of the two methods: LMT; 66.8/0%, LAD; 70.0/31.8%, LCx; 6.6/0%. RCA; 26.7/0%. 4) Coronary flow was detected by transesophageal two-dimensional Doppler in 73.3% of LMT, 76.6% of LAD, 6.6% LCx and 43.3% of RCA. 5) RCA flow was not detected by transesophageal two-dimensional Doppler in two patients who had complete obstruction of the proximal RCA although RCA near the orifice was obviously imaged by two-dimensional echocardiography. In conclusion, TED had an advantage over TTD in detecting coronary arteries and their blood flow, but TTD had an advantage over TED as to the visible length of coronary artery. When RCA near the orifice was clearly visualized, the absence of RCA flow by TED implied complete obstruction of the proximal RCA. PMID- 1930889 TI - [Effects of depth on the display of color Doppler flow imaging with transesophageal and transthoracic transducers: an experimental study]. AB - Transesophageal color Doppler flow imaging has proved to provide an accurate and sensitive information for diagnosis of valvular regurgitation. However, it is necessary to understand the difference in the display of color Doppler image between transesophageal and conventional transthoracic transducers for quantitative assessment of valvular regurgitation. In this study, the effects of the depth between transducer and jet flow on color Doppler flow imaging were evaluated with the transesophageal (3.75 MHz) and conventional (2.5 MHz) transducers by using a flow phantom. A flow circuit was filled with saline in which nylon corpuscles (average diameter; 5 microns) were suspended to enhance the Doppler effects. A turbulent jet with constant flow velocity (Reynolds number; 3500) stimulating valvular regurgitant flow was produced in a water bath through a small orifice (2 mm) by constant driving pressure (100 mmHg). Color jet imaging in the long- and short-axis views were observed at each depth with both transducers. The measurement was made every 1 cm in depth from 3 to 12 cm. The color gain setting was fixed at the optimal point so as to get the maximal flow image with the minimal static background noise. We obtained larger image of the color jet signal with the conventional than the transesophageal transducer. Although a mosaic pattern was displayed more distinctly with the transesophageal transducer compared with that of the conventional transducer, the transesophageal image tended to become indistinct in the depth deeper than 8 cm. On the other hand, the transthoracic image was maintained relatively constant at any depth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930890 TI - [Semi-quantitative evaluation of atherosclerotic lesions of the thoracic aorta with high resolution transesophageal ultrasound]. AB - This study was designed to assess semi-quantitative ultrasonic evaluation of atherosclerotic lesions with high resolution transesophageal ultrasound. Various types of atherosclerotic lesions were differentiated using transesophageal ultrasound in 51 samples from 20 specimens of fresh descending aorta of humans or other animals in vitro, and in 62 patients in vivo. Microscopic examination of normal, fatty plaque, fibro-fatty plaque, fibrous plaque, calcified lesion and ulcerative lesion apparently coincided with transesophageal ultrasound images of normal (0), intimal irregular thickening (degree of I), intimal protuberance with low and high echo density in the plaque (II), high echo density in the plaque having an additional echo layer in the medial layer (III), irregular intimal thickening with calcification and ulcerative lesion with low and high mixed echo (IV). The quality of ultrasound image obtained from the patients in vivo proved similar to that obtained during the in vitro studies, and in addition six ulcerative lesions including two with torn intima were detected with transesophageal echocardiography. These results demonstrate that high resolution transesophageal ultrasound is an excellent approach to detect semiquantitatively atherosclerotic lesions of the aorta in vitro and in vivo. PMID- 1930888 TI - [Quantitative evaluation of right ventricular function by transesophageal echocardiography: report of a case with classical right ventricular infarction]. AB - We were able to diagnose right ventricular infarction (RVI) by transesophageal echocardiography (TEE) in a patient with acute inferior infarction, and it was confirmed by cardiac catheterization. To evaluate right ventricular (RV) function quantitatively, area shortening (AS) and regional AS (rAS) were measured from RV images obtained by TEE. The AS correlated with RV ejection fraction obtained by radionuclide angiography (r = 0.72). The patient with RVI showed depressed RV function by AS measurement with decreased rASs of all regions in the acute phase. In the chronic phase, RV function of the patient improved, especially in the region of the ventricular septum and apex regions. These results indicate availability of TEE and that RV function can be evaluated by TEE. PMID- 1930891 TI - [Usefulness of transesophageal echocardiography in thoracic aortic disease: comparison with computed tomography and angiography]. AB - To evaluate the usefulness of transesophageal echocardiography in thoracic aortic disease, transesophageal echocardiography was performed in 11 patients with thoracic aortic disease (true aortic aneurysm in two patients, aortic dissection in nine patients). Findings obtained by transesophageal echocardiography were compared with those obtained by computed tomography (nine patients) and angiography (six patients). Results were as follows: 1. True aortic aneurysm: Although transesophageal echocardiography and computed tomography could evaluate the size of the aorta and detect mural thrombus, angiography underestimated degree of aortic dilatation because of the presence of mural thrombus. 2. Aortic dissection: Although computed tomography could not differentiate thrombus in the false lumen from mural thrombus in two patients, transesophageal echocardiography could discriminate those two easily in one patient from properties and motion of the intimal flap, and flow information in the false lumen. Angiography could not evaluate the range of dissection in any patients with thrombus in the false lumen. With transesophageal echocardiography we could detect the entry in all six patients with aortic dissection of DeBakey type III except 1 patient with aortic dissection of DeBakey type I. Transesophageal echocardiography could obtain real time image of most of the aorta except for a part of the ascending aorta. Therefore, transesophageal echocardiography was useful for diagnosing thoracic aortic disease and distinguishing between true aortic aneurysm and aortic dissection. PMID- 1930892 TI - [Estimation of atherosclerotic lesions in the thoracic aorta by transesophageal echocardiography]. AB - The thoracic aorta is one of the portions frequently involved with atherosclerotic lesions. We estimated atherosclerotic lesions in the thoracic aorta in consecutive 137 patients (59 +/- 10 years old) using transesophageal echocardiography. The study population consisted of 60 with coronary artery disease (CAD), 36 with hypertension (HT), 28 with hypercholesterolemia (HC, total cholesterol greater than or equal to 230 mg/dl), eight with dissecting aneurysm, nine with true aneurysm and two with aortitis syndrome. We used a single transverse scan-plane probe with ultrasound frequency of 5 MHz. We could obtain satisfactory echograms of whole thoracic aorta except upper portion of the ascending aorta. We defined atherosclerotic lesions as an increased echo-density of the intima, protruded plaque, ulceration or aneurysm. Atherosclerotic lesions were observed in 71 of 137 patients (52%). High incidence of the atherosclerotic lesions was seen in patients with HT (72%), HC (57%) and CAD (57%), whereas incidence of atherosclerotic lesions was low (15%) in patients without HT, HC, CAD or aortic aneurysm. Atherosclerotic lesions were observed more frequently in patients aged greater than or equal to 60 years (69% vs 34%, p less than 0.001). In patients with HT or HC, atherosclerotic lesions were frequently observed even in patients younger than 60 years old (HT: 58%, HC: 53%). We concluded that HT, HC and aging were important risk factors for the atherosclerotic process in the thoracic aorta, and transesophageal echocardiography was a useful approach for the detailed estimation of atherosclerotic lesions in the thoracic aorta. PMID- 1930893 TI - [Usefulness of high resolution transesophageal echocardiography for diagnosis of ruptured chordae tendineae of the mitral valve: clinical and echocardiographic characteristics]. AB - Transesophageal echocardiography with high resolution (TEE; 5 MHz, convex type probe) revealed ruptured chordae tendinae of the mitral valve (RCT) in seven patients. However transthoracic echocardiography (TTE) was diagnostic only in two patients. These all seven patients had mitral valve prolapse and mitral regurgitation documentated by TTE. Six of seven patients were 59 years or older, and four patients had only mild symptoms. TEE showed the systolic appearance of an edge echo, suggesting an edge of ruptured chordae tendineae within the left atrium. These results show that TEE is a useful method for detecting RCT of the mitral valve, especially in the aged patients with MVP and mitral regurgitation. It is because of the availability of high resolution and nearfield in TEE. PMID- 1930894 TI - [Evaluation of pulmonary venous flow pattern in hypertrophied and dilated hearts: a study with transesophageal pulsed Doppler echocardiography]. AB - In order to evaluate the clinical significance of pulmonary venous flow (PVF) pattern, transesophageal pulsed Doppler echocardiography (TEE) was performed in 25 patients with hypertrophied heart (all with hypertrophic cardiomyopathy), 15 patients with dilated heart (10 with old myocardial infarction and 5 with dilated cardiomyopathy) and 10 normal controls. Parameters obtained from the PVF pattern were compared with those of transmitral flow (MVF) pattern, % fractional shortening (%FS) of left ventricle (LV) and amplitude of mitral anular motion (MAM) during a cardiac cycle. Results were as follows: 1. PVF pattern in cases of sinus rhythm was divided into four components, atrial systolic backward flow (PVA), ventricular systolic (PVS1, PVS2) and diastolic (PVD) forward flows. 2. In patients with dilated heart, peak velocities of PVS1 and PVS2 were markedly decreased compared with those of hypertrophied and normal hearts. 3. Peak velocity of PVD in hypertrophied and dilated hearts was significantly decreased compared with that of normal controls, and PV-D/S (ratio of peak velocity of PVD to PVS2) was significantly lower in hypertrophied heart than in normal controls. 4. Time interval from the first heart sound to the peak of PVS2 (TS) was significantly longer in dilated heart, and time interval from the second heart sound to the peak of PVD (TD) was longer in hypertrophied heart than in the other two groups. 5. MAM and %FS of dilated heart were significantly lower than those in normal and hypertrophied hearts, and peak velocity of PVS2 in dilated heart group correlated well with MAM or %FS. 6. There were significant correlations among the diastolic parameters from PVD of PVF (peak velocity of PVD, PV-D/S) and early diastolic wave (D) of MVF (peak velocity, deceleration time and deceleration of rapid filling). 7. In a case of hypertrophic cardiomyopathy with mid-diastolic wave of MVF, distinct forward wave was observed after PVD of PVF, and this wave coincided in timing with the mid-diastolic wave of MVF. 8. In a case of extensive myocardial infarction with the development of severe LV dysfunction and with "normalized" pattern of MVF, peak velocities of PVD and PVA were markedly increased, and that of PVS2 was decreased. However, the peak velocities of PVD and PVA were decreased, and that of PVS2 was increased with the fair improvement of LV dysfunction and with the compensatory augmentation of atrial contraction wave (A) of MVF.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1930895 TI - [Pulmonary venous flow patterns in normal subjects and cardiac patients: a transesophageal echocardiographic study]. AB - The aim of this study is, first, to analyze pulmonary venous flow velocity (PVFV) pattern in normal subjects and second, to compare it with the various diseased state. PVFV was recorded in eleven normal volunteers, five patients with lone atrial fibrillation, twenty eight patients with valvular heart diseases and six patients with cardiomyopathy using transesophageal color Doppler echocardiography by placing the sample volume at the junction of the left superior pulmonary vein and left atrium. PVFV in normal subjects demonstrated distinct four waveforms: due to atrial systole (AS wave) and diastole (AD wave), and due to ventricular systole (VS wave) and diastole (VD wave). PVFV changed with respiration in normal subjects. The peak velocity of VD wave was increased with inspiration (p less than 0.001). The ratio of velocity VS/VD was increased during expiration (p less than 0.01). The ratio of area AD + VS/VD was significantly decreased with inspiration (p less than 0.01). We feel that this is the normal variation in pulmonary venous return during respiration , influenced by changes in the venous return on the right side of the heart. In all patients with atrial fibrillation, AS and AD waves were disappeared. The negative deflection occasionally observed was due to mitral valve closure. In patients with mitral stenosis, the peak velocity of VD wave was significantly decreased compared to that of normal subjects, but it was not significantly different between the patients with mitral valve replacement and normal subjects. The peak velocity of VD wave was also correlated with pressure half time among the patients with mitral stenosis, mitral valve replacement and mitral commissurotomy. On the other hand, it was significantly increased in patients with mitral regurgitation and returned to normal level after the operation. The peak velocity of VS wave was correlated with the left atrial dimension among the patients with mitral valve diseases except these with mitral regurgitation. In patients with mitral regurgitation, the peak velocity was decreased compared to that of normal subjects and reversed flow was seen in half of the patients. Also, it was decreased in patients with dilated cardiomyopathy and increased in patients with hypertrophic cardiomyopathy. In conclusion, PVFV is influenced not only by changes of venous return with respiration but also by the left atrial size, presence or absence of MS or MR, left atrial or left ventricular systolic and diastolic function in the various diseased states. PMID- 1930896 TI - Activity in anticipation and in succession of a daily meal. AB - When exposed, in otherwise constant conditions, to a schedule with one single meal per day, rodents anticipate the time of food availability by an increase in locomotor activity while the main circadian rhythm continues to free-run with a period different from 24 h. The anticipatory activity (AA) is considered a component which is uncoupled from the light-entrainable circadian system and controlled by a food-entrainable oscillator. In this report it is shown that, in addition to AA, sometimes a burst or band of activity appears which succeeds the feeding time (SA). AA and SA seem to belong to one another, both being controlled by the same food-entrainable oscillator. The band of activity constituted by the combination of both AA and SA, though temporarily suppressed during and immediately after the meal, follows, as a whole, the rules of entrainment as known from circadian systems. PMID- 1930897 TI - Analytical morphies on mid-sagittal craniograms glabella-opisthocranion of Homo erectus and Homo sapiens neanderthalensis: Fourier parameters and synthesis of mean craniograms. AB - Among mathematic procedures used in morphological description, Fourier analysis was indicated as extremely effective in obtaining numerical representations of shape. In order to fully exploit its potentiality in morphology the worked data have to be referred exclusively to the shape of the investigated object and the application of suitable procedures of dimensional normalization are necessary, moreover the significance of the parameters obtained from the analysis must be referable univocally to the morphological datum. In these conditions the numerical characterization of shapes and the relations detectable from different parameters obtained from the description assume the significance of real "analytical morphies". These statements were verified by performing morphological description and comparison, by means of the Fourier harmonic analysis on two groups of mid-sagittal glabella-opisthocranIon craniograms to point out their possible distinctive analytical characteristics: the first group relates to classical neanderthalian group, the second one is made up of asiatic samples of Homo erectus. Some typical patterns of the obtained parameters were discussed and explained in terms of analytical morphies characterizing the given specimens, the traditional morphological classifications were verified and, above all, a numerical description of these samples was obtained. PMID- 1930898 TI - Analytical morphies on mid-sagittal craniograms glabella-opisthocranion of Homo erectus and Homo sapiens neanderthalensis: Fourier parameters and multivariate discriminant analysis. AB - The analytical description of complicated morphologies offers the possibility to define patterns of parameters characterizing the investigated groups. These patterns must be considered as morphies useful in performing classification and comparison. Fourier parameters are extremely effective in describing and comparing complex irregular forms and since they are statistically independent we can use them in performing multivariate discriminant analysis. Two groups of mid sagittal craniograms glabella-opisthocranion of asiatic samples of Homo erectus and of Homo sapiens neanderthalensis were described by means of Fourier harmonic analysis. The discriminatory power of all the obtained parameters (coefficients, amplitudes and phases) was tested. A discriminant function (error % = 0) was obtained using as parameters the first 4 sine/cosine coefficients, the 5th sine, the 6th and the 7th cosine components (11 parameters in all). When the information contained in the coefficient values is being subdivided into the two components of amplitude and phase, the amplitude component is not able to discriminate between the two groups (error % = 25), while the phase values of the first 7 harmonics are able to discriminate them (error % = 0 and distance between centroids = 47). PMID- 1930899 TI - [Evaluation of the characteristics and performance of an automatic sphygmomanometer (Omega 1400)]. AB - 24 hour pressure monitoring is a newly developing technique potentially yielding important informations in hypertensive patients. Numerous automated devices are available whose performance characteristics are poorly documented. To evaluate an automated sphygmomanometer commonly used in our Division (Omega 1400, Invivo Research Laboratories), we performed a series of measurements, simultaneously recording blood pressure in the opposite arm with a common sphygmomanometer. Each measure was then repeated reversing the position of the two devices (manual and automated), thus abolishing possible differences between the two arms. We observed a mean underestimation of 1.90 mmHg of systolic pressure and of 4.82 mmHg of diastolic blood pressure by the automated device. We conclude that the device by us evaluated is not advisable in the basal blood pressure evaluation, but useful in monitoring inpatients. PMID- 1930900 TI - [Blood pressure monitoring during hospital convalescence]. AB - Blood pressure ambulatory monitoring has provided numerous and interesting informations on the clinical as well as investigational setting of arterial hypertension. The vast majority of data have been obtained registering blood pressure during the normal daily activities of the patients and surprisingly few studies have been undertaken to evaluate blood pressure behaviour in inpatients. We observed the 24 hours pattern of blood pressure in hypertensive and normotensive inpatients, using an automated sphygmomanometer (Omega 1400), whose performance was previously evaluated by us. The results demonstrate that blood pressure monitoring in inpatients could be a useful tool in managing hypertensive patients. PMID- 1930901 TI - [Central and peripheral monitoring of the cellular redox state after reduced glutathione administration in the rat]. AB - In this study we measured reduced glutathione as DTNB reactive material in different brain areas as well as in liver and kidney of rat, before and after exogenous administration of GSH. Treatment with GSH produced an increase in DTNB positive material as well as a decrease of lipoperoxidation, in central and peripheral organs of rat, suggesting the possibility of an exogenous modulation of redox balance in mammalian cells. PMID- 1930903 TI - [The gastric mucosa of the human fetus. II. Ontogenesis of the gastric glands in the strict sense]. AB - The ontogenesis of the gastric glands of the fundus-corpus zone (oxyntic glands), in 37 human foetuses ranging from 9 to 16 weeks of gestational age, has been studied by light and electron microscopy. At 9 weeks of age the gastric mucosa already shows numerous and well developed gastric pits. Between 9 and 12 weeks of age, the proliferation of the epithelial cells at the bottom of the gastric pits gives rise to the glandular buds; the glandular lumen comes out later, at 13-16 weeks of age. The differentiation of the epithelial cells in the developing oxyntic glands does not occur simultaneously; on the basis of their morphological distinctive features it is possible to distinguish four principal types of epithelial cells: the endocrine cells are already present at 9 weeks of age; the parietal cells appear at 11-12 weeks; whereas the mucous neck cells and the zymogen cells can be recognized from the 12th week. During the studied gestational period no morphological sign of active exocrine secretion of oxyntic glands has been observed. PMID- 1930902 TI - [Evaluation of a new immunoturbidimetry technique for measuring microalbuminuria]. AB - Subclinical elevation of urinary albumin excretion is a good predictor of later clinical proteinuria. A simple, sensitive and rapid immunoturbidimetric method was developed to quantify urinary albumin excretion (URIN-PAK ImmunoMICRO LAB, Miles Italia Spa). In the presence of polyethylene glycol 6000, immunocomplex between human albumin and its specific antibody are rapidly formed (5-50 min, at room temperature). Absorbance reading are mode U 340 nm (Automatic Analyzer RA 1000, Technicon). The test is specific for albumin failing to cross react with other plasma proteins present in urine, as well as with glibenclamide, chlorpropamide, phenformin, hemoglobin, glucose, urea and thymol. The present method correlates with SCLAVO H-ALBUMIN RIA Kit (r = 0.9917). The test is suitable for clinical use. PMID- 1930904 TI - [Peptidase activity and toxicity of strains of Pseudomonas aeruginosa]. AB - Pseudomonas aeruginosa is a microorganism of the terrestrial and aquatic environment which may cause pulmonary, urinary and corneal infections. The pathogenesis of Pseudomonas-induced diseases seems to be linked to the production of extracellular substances such as exotoxins, hemolysins, leukocidins and hydrolytic enzymes, including various peptidases. Anyway there is not a clear view on the role other proteases have in the mechanism of pathogenesis, and even if their activity may always be associated to the toxicity of the microorganism. We have therefore determined the activity of a number of eso- and endopeptidases in 17 strains of P. aeruginosa isolated from patients with urinary pathologies. Four of these peptidase activities, namely elastase, neutral protease, aminopeptidase I and leucine aminopeptidase show a positive correlation with three parameters selected as indices of toxicity, i.e. the mucoid appearance, the gentamicin resistance and the adhesivity of colonies. PMID- 1930905 TI - [Complement behavior in rats bearing Yoshida tumors subjected to treatment with gonadotropin and PGE2]. AB - The haemolytic activity of the total Complement (CH50) and the fractions C3 and C4 were assayed in rats transplanted with Yoshida's tumor and then treated with hCG, LH-FSH and PGE2. A relevant increase, only concerning the values of the CH50 and C3 fraction, was observed in all animals in the early days after the transplantation, probably due to a sort of stress "by transplantation". Afterwards, hCG and PGE2 induced an increase in CH50 and C3 values, but not in the C4 fraction. Treatment with LH and FSH led to a very slight increase in the CH50 and C3. In the following days, as a consequence of the cachexia, a progressive reduction of the values of the Complement was observed in all animals. Those treated with hCG also showed a little increase of survival. The authors suggest that the increase in CH50 and C3 fraction induced by the treatment with hCG and PGE2 could be an expression of increase of the aspecific humoral immunity, as a compensatory mechanism of the cell-mediated immunological depression which occurs during neoplasias. PMID- 1930906 TI - [Effect of the cervical reflex on the posture of normal subjects. Balance measurement study]. AB - The little we know about the existence and the meaning of the cervical component on the vestibulo-spinal reflex, led us to carry out a study on normal subjects examined by computerized stabilometry with the head turned 75 degrees left and right, in order to check the postural alterations during the stimulation of the neck proprioceptors. The results show a significant increase of the values of the LTT, SE and Vm with the head turned to the left; the increases were not significant with the head turned to the right. The difference is difficult to explain. The results show that in man too the posture is affected by reflex of cervical origin. PMID- 1930907 TI - [Nasal provocation test with hyperosmolar solutions: normal values]. AB - Hyperosmolar solutions have recently been introduced as test-substances in the nasal provocation of vasomotor rhinitis subjects. In order to establish a norm, the test was carried out in 40 subjects without nasal pathologies, stimulating with solutions at increasing level of concentrations of NaCl (0.9% - 1.8 - 3.6% - 5.4% - 7.2% - 9%). In all subjects an increase in nasal secretion was verified in proportion to the concentration of the solutions and this increase was statistically significative, with respect to the base, from the concentration 3.6% (p less than 0.001) on words. The statistical analysis has not, however, evidenced any significant differences in secretion between male or female subjects. As far as the variation of nasal resistance is concerned, the rhinomanometric registration has revealed that the hypertonic solutions modify such resistances in a rather casual, absolutely irregular and unimportant way. These results lead to believe that the test is extremely useful in the study of the secretion component of vasomotor rhinopathy. PMID- 1930908 TI - [Nasal provocation test with histamine: rhinomanometry study of normal subjects]. AB - Nasal reactivity to histamine was evaluated in 40 normal subjects. The application of a chloride histamine solution (1 mg) registered in 90% of the subjects the appearance of sneezing with the number of sneezes ranging between one and fourteen (5.7 +/- 3.76) and an average increase in the total resistence in the inspiration phase of 93.1% (+/- 63.2) and in the expiration phase of 98.1% (+/- 60.5) with a range between 37.7% and 24.1%. The authors conclude that sneezing and above all nasal congestion evaluated rhinomanometrically represent two important parameters in the evaluation of nasal reaction; an increase greater than or equal to 200% of the total nasal resistance can surely be considered an index of nasal hyperreactivity. PMID- 1930909 TI - Bronchofibreoscopy in anaesthesia and intensive care. PMID- 1930911 TI - Cytokines in rheumatoid arthritis. AB - Joints with rheumatoid arthritis are a site for chronic inflammation involving T cells, B cells, macrophages and dendritic cells. When these cells interact cytokines are likely to be produced. The presence of different cytokines in the synovial fluid of patients with rheumatoid arthritis has been studied and the macrophage derived cytokines such as IL-1, IL-6, TNF-alpha, TGF-beta and PDGF have usually been detected in large quantities, whereas T cell produced cytokines (IL-2, IL-4, IFN-gamma) are absent or present in small quantities. IL-1, IL-6 and TNF-alpha have several functions which suggest that they participate in the chronic disease process of rheumatoid arthritis, such as increasing production of eicosanoid, collagenase and prostaglandin E2. Many synovial B cells are activated and produce large amounts of immunoglobulins. We searched for a B cell stimulatory activity in rheumatoid synovial fluid and found a B cell differentiation and helper activity. Cytokines in the joints of patients with rheumatoid arthritis seem central for the propagation of the disease process. Specific intervention in cytokine production or in its effects might help to relieve symptoms in rheumatoid patients. PMID- 1930910 TI - Matrix in cartilage and bone development: current views on the function and regulation of major organic components. AB - Study of the growth and development of cartilage and bone has been difficult because the structure of the tissues makes biological experiments hard to conduct. Recent advances in molecular biology have offered new possibilities for studying these processes. Many cartilage and bone specific cDNAs have been cloned and characterized and consequently used to localize the corresponding mRNAs in tissue sections. Developing cartilage and bone serve as a model for the study of extracellular matrix gene regulation during the proliferation, growth and differentiation of connective tissue cells. Normal skeletal growth and development are regulated by both systemic and local factors. The effects of many systemic hormones on bone metabolism have been studied extensively, but the pathways triggered by these hormones in the target cells are less well known. Recent evidence suggests that some growth factors, such as TGF-beta, IGFs and PDGF, act as local regulators of cartilage and bone metabolism. The different extracellular matrix components, e.g. collagens, are expressed differently in distinct cell types and developmental stages during cartilage and bone development. This model, therefore, facilitates the study of relations between the production of the various extracellular matrix components and the growth factors and the proto-oncogenes which may regulate them. Existing knowledge of the expression of major cartilage and bone components and their regulation during growth, differentiation and development is reviewed. An understanding of the normal growth and development of cartilage and bone is fundamental for elucidating the mechanisms underlying the various diseases -- both hereditary and acquired -- affecting the human skeleton. PMID- 1930912 TI - The aetiology of dizziness and how to examine a dizzy patient. AB - Dizziness embraces various sensations of spatial disorientation. A common symptom, it has been experienced by at least one third of the population by the age of 65. Peripheral causes include disorders of the labyrinth and vestibular nerve such as Meniere's disease, benign paroxysmal positional vertigo, acute vestibulopathy (vestibular neuronitis) and acoustic neuroma. The most common lesions of the central nervous system that cause dizziness are infratentorial ischaemia, mechanical trauma, multiple sclerosis and cerebellar atrophy. Other aetiological factors include intoxications, psychogenic causes, cervical problems and cardiovascular diseases. The history and physical examination are the cornerstones of the search for the cause of dizziness. The most valuable otological methods are electronystagmography and audiometry. Of the clinical neurophysiological methods, brainstem auditory evoked potentials are more useful than electroencephalography. Computed tomography and magnetic resonance imaging should be used when a CNS disorder is suspected. PMID- 1930913 TI - Cloning of Alport syndrome gene. PMID- 1930914 TI - Polyamines: from molecular biology to clinical applications. AB - The polyamines putrescine, spermidine and spermine represent a group of naturally occurring compounds exerting a bewildering number of biological effects, yet despite several decades of intensive research work, their exact physiological function remains obscure. Chemically these compounds are organic aliphatic cations with two (putrescine), three (spermidine) or four (spermine) amino or amino groups that are fully protonated at physiological pH values. Early studies showed that the polyamines are closely connected to the proliferation of animal cells. Their biosynthesis is accomplished by a concerted action of four different enzymes: ornithine decarboxylase, adenosylmethionine decarboxylase, spermidine synthase and spermine synthase. Out of these four enzyme, the two decarboxylases represent unique mammalian enzymes with an extremely short half life and dramatic inducibility in response to growth promoting stimuli. The regulation of ornithine decarboxylase, and to some extent also that of adenosylmethionine decarboxylase, is complex, showing features that do not always fit into the generally accepted rules of molecular biology. The development and introduction of specific inhibitors to the biosynthetic enzymes of the polyamines have revealed that an undisturbed synthesis of the polyamines is a prerequisite for animal cell proliferation to occur. The biosynthesis of the polyamines thus offers a meaningful target for the treatment of certain hyperproliferative diseases, most notably cancer. Although most experimental cancer models responds strikingly to treatment with polyamine antimetabolites--namely, inhibitors of various polyamine synthesizing enzymes--a real breakthrough in the treatment of human cancer has not yet occurred. It is, however, highly likely that the concept is viable. An especially interesting approach is the chemoprevention of cancer with polyamine antimetabolites, a process that appears to work in many experimental animal models. Meanwhile, the inhibition of polyamine accumulation has shown great promise in the treatment of human parasitic diseases, such as African trypanosomiasis. PMID- 1930915 TI - Effect of moderate freshwater fish diet on erythrocyte ghost phospholipid fatty acids. AB - Dose responses over 12 weeks of meals containing fish on erythrocyte phospholipids were studied in male students. In all major glycerophospholipids the proportions of long chain n-3 fatty acids increased at the expense of n-6 fatty acids with 1.5 meals a week containing fish (0.5 g n-3 fatty acids per day). The rates and magnitudes of changes varied for individual phospholipids: faster but quantitatively smaller changes occurred in phosphatidylcholine than in phosphatidylethanolamine and phosphatidylserine. Fish diet and fish oil studies have usually been made using large doses over a short time. Our results show that similar effects might result from smaller amounts given over a longer time. PMID- 1930917 TI - Introduction to the symposium: physical activity and hypertension. PMID- 1930916 TI - Transdermal and oral clonidine. AB - The antihypertensive efficacy and side effects of transdermal clonidine (Catapres TTS) and oral clonidine in equivalent doses on a weight basis were compared under double blind (double dummy) and cross over conditions in 16 outpatients with mild to moderate hypertension. After four weeks of placebo TTS and placebo tablet treatment, the patients were randomly placed into groups for six weeks of active treatment and, after an intervening week of placebo treatment, a second six week treatment period. Transdermal clonidine reduced supine and standing blood pressures (P less than 0.01) and heart rates (P less than 0.05) compared with the values at the end of the placebo periods, while oral clonidine did so to the extent of supine systolic blood pressure (P less than 0.01) and standing heart rate (P less than 0.05), respectively. There were, however, no differences in the values between transdermal and oral clonidine at the end of these six week periods. The plasma clonidine concentration was lower 12 hours after a dose of oral clonidine than after transdermal clonidine (P less than 0.05). The side effects did not differ. Seven patients said afterwards that they preferred the transdermal treatment, two preferred the oral treatment and four could not state any preference. It is concluded that transdermal clonidine is similar in its effect to oral clonidine in mild to moderate hypertension. Transdermal clonidine once a week may increase patients' compliance with antihypertensive treatment. PMID- 1930918 TI - Exercise prescription for hypertensive patients. AB - Physical conditioning has been suggested as a useful adjunct or alternative to pharmacologic therapy in the treatment of borderline or mild hypertension. This recommendation stems from numerous studies that have demonstrated modest decreases in blood pressure in hypertensive individuals. Exercise guidelines should be based on preliminary exercise testing and modified to accommodate those patients who are taking a variety of antihypertensive medications. Although pure isometric exercise is generally contraindicated in hypertensive patients, potentially valuable training activities that involve a substantial static component, including arm crank ergometry and mild-to-moderate load weight training, probably requires individual assessment. PMID- 1930919 TI - Effect of exercise on pharmacokinetics. AB - The increasing popularity of sporting events, even for people on drug treatment, has raised the question of the interaction of exercise and pharmacokinetics. Exercise reduces splanchnic blood flow, but possible changes in the absorption of orally given drugs seem to be of minor clinical significance. Absorption from intramuscular, subcutaneou and transdermal application sites may be accelerated by exercise, possibly causing harmful consequences, e.g. in diabetics treated with insulin. Exercise or physical work increases the rate and depth of respiration thus increasing alveolar exchange of gases and vapours. Physical activity increases muscular blood flow and the binding of digoxin to muscular structures, with a simultaneous fall in the concentration of serum digoxin. Reduction in blood flow to adipose and other inactive tissues may delay the distribution of some drugs that are stored or removed by these tissues. The change from supine to upright position can affect the distribution of a drug. Exercise reduces the blood flow in the liver and deactivation of drugs with flow limited (high clearance) hepatic metabolism such as nitrates and lidocaine. Metabolism of capacity-limited (low clearance) drugs, e.g. antipyrine, diazepam and amobarbital, is not influenced by exercise. Renal plasma flow, urine excretion rate and urine pH are also reduced by exercise. This is an important reason why the serum levels of drugs eliminated through the kidneys increase during physical stress. The changes in parenteral absorption and distribution volume of some drugs caused by exercise, as well as the short half-life of drugs, are properties resulting in altered therapeutic/toxic response in those drugs with a narrow therapeutic range. PMID- 1930920 TI - Dietary fats, antioxidants and blood pressure. AB - Although obesity and alcohol intake as well as dietary sodium, potassium and magnesium are the major non-genetic determinants of blood pressure levels, interest has recently been stimulated in the function of fatty acids and antioxidants in the aetiology of hypertension. In the Kuopio Ischaemic Heart Disease Risk Factor Study both plasma ascorbic acid and serum selenium concentrations had a moderate, independent inverse association, estimated dietary intake of saturated fatty acids had a positive association and estimated dietary intake of linolenic acid had an inverse association with the mean resting blood pressure in 722 Eastern Finnish men with neither self reported hypertension nor cerebrovascular disease. Even though these cross sectional observations do not prove causality, they warrant clinical trials to verify or disprove that dietary fats and antioxidants are factors in the development of hypertension. PMID- 1930921 TI - Minerals and blood pressure. AB - The mineral elements sodium, potassium, calcium and magnesium play a central role in the normal regulation of blood pressure. In particular, these mineral elements have important interrelationships in the control of arterial resistance. These elements, especially sodium and potassium, also regulate the fluid balance of the body and, hence, influence the cardiac output. Evidence shows that the present levels of intake of mineral elements are not optimum for maintaining normal blood pressure but predispose to the development of arterial hypertension. Research results suggest that without sodium chloride (common salt) and other sodium compounds being added to the diet arterial hypertension would be virtually non existent. Moreover, blood pressure would not rise with age. In communities with a high consumption of added sodium, a high intake of potassium and, possibly, magnesium seem to protect against the development of arterial hypertension and the rise of blood pressure with age. A marked reduction of sodium intake is effective in treating even severe hypertension. A moderate restriction of sodium intake or an increase in potassium intake exert remarkable antihypertensive effects, at least in some hypertensive patients. Magnesium and possibly also calcium supplements may be effective in reducing blood pressure in some hypertensives. In hypertensive patients treated with drugs sodium restriction and potassium and magnesium supplementation enhance the therapeutic effect, reduce the number and dosage, and lessen the adverse effects of prescribed antihypertensive drugs. Hence, a fall in sodium consumption and increases in potassium and magnesium consumption are useful in preventing and treating arterial hypertension. PMID- 1930922 TI - Physical fitness and all-cause mortality in hypertensive men. AB - All-cause death rates in normotensive and hypertensive men were examined across physical fitness levels. Subjects were 10,224 healthy normotensive men and 1,832 men who reported a history of hypertension, but were otherwise healthy. Physical fitness was determined by maximal treadmill exercise testing. Baseline preventive medical examinations were given during 1970-1981, and mortality surveillance was conducted on the cohort through 1985. There were 240 deaths in the normotensive men and 78 deaths in hypertensive men. Age-adjusted all-cause mortality rates per 10,000 man-years of follow-up in normotensive men ranged from 64.0 in the least fit quintile to 18.6 in the most fit quintile. Corresponding rates for hypertensive men were 110.5 to 24.8. Subjects were further classified into lower and higher blood pressure groups by baseline resting systolic blood pressure (less than 140 mmHg and greater than or equal to 140 mmHg). Normotensive and hypertensive men who were more fit had lower death rates compared to less fit men within both of the measured blood pressure strata. The relation between fitness and all-cause mortality held in multiple logistic regression analyses after adjustment for the influence of age, serum cholesterol, resting systolic blood pressure, body mass index, current smoking habit, and length of follow-up. We conclude that low levels of physical fitness result in an increased risk for all cause mortality in normotensive and hypertensive men. PMID- 1930923 TI - What is the dose-response relationship between exercise training and blood pressure? AB - Most studies of exercise and blood pressure have used a standard exercise programme with a single level of physical activity. To determine the nature of the dose-response relationship however it is necessary to examine several levels of activity, preferably in the same subjects. We have recently performed several randomised crossover studies comparing different levels of regular exercise. The intensity and duration of exercise bouts were constant throughout the studies, but their frequency was varied. Standard bouts consisted of 30 min of bicycling at 60%-70% of maximum work capacity. The exercise was performed either three weekly or 7-weekly in randomised order and each level was maintained for one month. In sedentary normal subjects three bouts of exercise/week for a total of 90 min lowered blood pressure by 10/7 mmHg. With seven bouts, i.e. a total of 210 min exercise/week, blood pressure was only slightly lower than 3-week exercise and was 12/7 mmHg below sedentary values. Responses to measures of physical fitness including maximum oxygen consumption and work capacity were linearly related to the amount of exercise performed each week. Similar results were obtained in hypertensives. Another randomised study was performed amongst expeditioners to Antarctica where environmental conditions determined that they were sedentary in winter and active in summer. The addition of either 3-week or 7 week exercise in winter significantly lowered blood pressure. In summer when the background level of activity was higher, blood pressure with no added exercise was similar to exercising levels in winter. There was no further fall in blood pressure with either 3-week or 7-week additional exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930924 TI - Physical activity and hypertension: an epidemiological view. AB - We examined patterns of physical activity and other characteristics that might deter hypertension or delay all-cause mortality among university alumni, 1962 1985. Collegiate sports play did not alter hypertension incidence, nor did contemporary walking, stair-climbing, or light sports play among 5463 University of Pennsylvania alumni, 739 of whom developed hypertension. But vigorous sports play reduced hypertension incidence; and overweight, gain in weight, history of parental hypertension, or any combination of these, increased it. Among 819 hypertensive Pennsylvania alumni (138 died during follow-up), vigorous sports play had minimal influence on mortality; but freedom from overweight and cigarette smoking deferred death. Among 16,936 Harvard College alumni, of whom 2614 died during follow-up, lack of vigorous sports play, or presence of hypertension, cigarette smoking, and overweight increased risk of premature mortality, heightened by any combination of these adverse characteristics. Overall, we found an inverse relationship between vigorous sports participation and hypertension risk but a direct relationship between risk and weight-for height, weight gain, or parental hypertension. With regard to all-cause mortality, cigarette smoking and hypertension were most hazardous for the individual; smoking and lack of vigorous recreational play were most hazardous for the alumnus population as a whole. PMID- 1930925 TI - Blood pressure regulation during exercise. AB - This brief review examines five problems concerning arterial blood pressure regulation during exercise. These are: 1. A history and summary of evidence that baroreflexes are, or are not, active during exercise. 2. What might be other "regulators" of blood pressure during exercise? The characteristics of a blood pressure-raising reflex from ischemic and active skeletal muscle (muscle chemoreflex) is reviewed along with a putative role for centrally generated motor command signals (central command). 3. How blood pressure is maintained during exercise. The importance of regional vasoconstriction, particularly in active skeletal muscle, is reviewed. 4. How well matched are cardiac output and total vascular conductance? Does demand for muscle blood flow outstrip cardiac pumping capacity? 5. Reflex control of blood pressure by both baroreflexes and muscle chemoreflexes. The importance of baroreflexes and evidence for resetting is reviewed. A new hypothesis is stated. PMID- 1930926 TI - Hypertension in diabetic patients--use of exercise in treatment. AB - Prevalence of hypertension is greater than normal in patients with type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes. In those with type 2 diabetes insulin resistance and hyperinsulinaemia may play a part in the pathogenesis of hypertension independent of obesity. Regular physical activity increases insulin sensitivity through its effect on glucose utilisation in peripheral (muscle) tissue. Furthermore, physical activity helps control weight, and it may reduce blood pressure and, serum cholesterol and triglycerides concentrations while increasing the amount of high-density lipoprotein cholesterol. So physical exercise programmes should be included in the management of patients with type 2 diabetes. Suitable exercise forms and programmes can be prepared for most patients. PMID- 1930927 TI - Muscle fibre types, ubiquinone content and exercise capacity in hypertension and effort angina. AB - The composition of skeletal muscle fibre expressed as a percentage of slow twitch (ST), type I or "red" and fast twitch (FT), type II or "white" were determined in patients with hypertension (HT) or with severe ischaemic heart disease (IHD) and compared to age matched controls. Similarly, exercise capacity expressed as the cycle intensity eliciting a blood lactate concentration corresponding to 2.0 mmol x 1-1 were compared with healthy controls. Both patient groups had a higher percentage of FT fibres with relatively lower exercise capacities than their controls. The exercise capacities were reduced even when the relationship of decreased capacity with the percentage of increased FT was considered. There was an increase IHD but not in HT in patients with fibre subgroup FTc, which most probably reflected fibre trauma. Both patient groups were low in the skeletal muscle mitochondrial electron carrier and unspecific antioxidant ubiquinone, coenzyme Q10 or CoQ10. Patients with IHD but not HT showed, however, a faster fall in the ratio CoQ10 over ST% the higher the percentage value of ST. The ratio reflects the antioxidant activity related to CoQ10 in the fibre hosting most of the oxidative metabolism. A low ratio indicates a risk of metabolic lesion and cell trauma. This could explain fibre plasticity and offer an alternative cause to heredity in elucidating in deviating muscle fibre composition in patients with HT and IHD. PMID- 1930928 TI - Hypertension, plasma lipids and antihypertensive drugs. AB - Treatment of hypertension is quite effective in preventing cerebrovascular disease. Morbidity and mortality from coronary heart disease, the major complications of high blood pressure are not, however, generally affected when mild to moderate hypertension is treated with antihypertensive drugs. This is probably owing to the multifactorial nature of atherosclerosis, the main cause of coronary heart disease. For example, dyslipidemias and other risk factors are very common among hypertensive patients. Prevention of coronary heart disease among hypertensive subjects is possible only by intervening in the many contributory risks. Non-pharmacological hypolipidemic treatments such as adequate nutrition and exercise are positive steps in the treatment of all hypertensive patients. The role of various antihypertensive agents should also be carefully considered. The associations between hypertension, several metabolic abnormalities, development of organ complications and various antihypertensive drugs should be explored in detail. PMID- 1930929 TI - The clinical significance of Helicobacter pylori infection in chronic dyspepsia and peptic ulcer disease. PMID- 1930930 TI - Population screening for colorectal cancer, the goals and means. AB - The causes of colorectal cancer are complex and in most cases obscure, making primary prevention impossible at present. Secondary prevention by finding and treating early asymptomatic cancers may possibly reduce mortality from this very common cancer. Results from conventional treatment have changed little during recent decades and are unsatisfactory, with more than half of the patients dying from the disease. The incidence has increased during recent years in many countries, making it vital to evaluate possible benefits from screening. This review considers different methods of screening for colorectal cancer and includes an overview of continuing European controlled randomised trials with the faecal occult blood test, Haemoccult-II. No final evaluation is possible, but advantages and drawbacks of different strategies are discussed. Assuming that the goal of reducing mortality is achieved, several other problems remain unsolved: the organisation of screening, the training of doctors in endoscopy, cost benefit and cost effectiveness all of which will have to be solved before a population screening can be recommended. Present screening tools are not ideal and we have to continue the search for better markers of early colorectal cancers and even possible precursors like adenomas. PMID- 1930931 TI - New microbial diagnosis. AB - Rapid methods for comprehensive nucleic acid analysis are essential for the progress in basic research. In microbial diagnosis nucleic acid analyses are useful for achieving quick, sensitive results with new dimensions of specificity. As to specificity, hybridisation tests are easily constructed for genus or species specific microbial typing or for the detection of genes accounting for pathogenic properties. Modern sequence analysis allows rapid detection of mutations eg., those conferring antiviral resistance. A new level of sensitivity comparable to that of the conventional enrichment culture is obtainable by enzymatic amplification (PCR) of microbial nucleic acids before detection. PCR technology has proved particularly useful in the diagnosis of microbial infections when the organisms are impossible or tedious to cultivate. For reliable diagnostic use the performance of in vitro amplification requires extreme care to prevent false positive results owing to carry over problems. In conclusion, nucleic acid analyses are expanding the potential for diagnosing microbial infections and may well replace some conventional diagnostic methods. PMID- 1930932 TI - The management of acute severe ulcerative colitis. PMID- 1930933 TI - Concept of one gene one protein revisited: protein disulphide isomerase, a multifunctional protein. PMID- 1930934 TI - Marfan gene discovered. PMID- 1930936 TI - Gastric Helicobacter and upper gastrointestinal symptoms in chronic renal failure. AB - We studied histologically antral biopsies from 89 consecutive patients with chronic renal failure for Helicobacter pylori (previously Campylobacter pylori). A dose-response gastric secretion test was also performed. The frequency of Helicobacter-positive subjects was low (15/89, 17%), corresponding to figures reported in the literature for young symptomless volunteers. Helicobacter positive patients had significantly more frequently upper gastrointestinal symptoms than Helicobacter-negative individuals (P less than 0.05). Antral gastritis was more common in the Helicobacter-positive than in the Helicobacter negative renal patients (P less than 0.01), but the incidence of body gastritis did not differ between them. The Helicobacter-positive patients had lower serum urea levels (P less than 0.01) and higher acid outputs (P less than 0.001) than Helicobacter-negative subjects. All patients had raised fasting serum gastrin levels, which possibly obscured the difference between Helicobacter-positive (283 pg/ml) and -negative (331 pg/ml) patients. We conclude that in chronic renal failure gastric colonization of Helicobacter pylori is not more frequent than usual. It correlates positively with antral gastritis, gastric acid output and upper gastrointestinal symptoms, but negatively with serum urea levels. PMID- 1930935 TI - Effect of changes in weight-bearing exercise on lumbar bone mass after age fifty. AB - This two year longitudinal study of 40 healthy subjects over age fifty (27 exercisers, 13 non-exercisers) was designed to evaluate the impact of weight bearing exercise on lumbar bone mineral density as assessed by quantitative computed tomography. In both males and females exercising at moderate levels, a high correlation was found between changes in exercise and changes in bone density (r = 0.78 and 0.91, respectively P less than 0.002). For extreme levels of exercise (greater than 300 min/week in females over age fifty, and greater than 200 min/week in males over age seventy) bone density was low, confirming earlier cross-sectional results. Subjects without change in their exercise levels and non-exercisers lost similar amounts of bone. Increasing body mass index was identified as a protective factor with regard to lumbar bone loss. We conclude that in exercisers continuation of weight-bearing exercise is mandatory to prevent excessive bone loss. Extreme levels of exercise may be detrimental to bone density in subjects over age fifty years. PMID- 1930937 TI - Multiple changes in apoprotein B containing lipoproteins after ethanol withdrawal in alcoholic men. AB - The plasma concentrations and chemical compositions of the apolipoprotein B containing lipoproteins (VLDL, IDL and LDL) were studied in 29 male alcoholic subjects at the end of a drinking period and in 17 healthy controls. No difference was found in the concentrations of plasma total cholesterol and triglyceride between the alcoholics and the controls, whereas plasma HDL cholesterol and VLDL triglycerides were 90% and 73%, respectively, higher in the alcoholics. The VLDL cholesterol:triglyceride ratio was reduced by 32%, whereas VLDL protein:cholesterol and phospholipid:cholesterol ratios were increased by 36% and 46%, respectively. IDL mass and protein concentrations, and particularly the fractional cholesteryl ester content of IDL tended to be low in the alcoholics. The plasma concentrations of all the LDL components except triglycerides were reduced in the alcoholics, resulting in a lower LDL cholesterol:triglyceride ratio. During the four day abstinence, when the lipoprotein values were followed in 15 alcoholic subjects, the abnormalities in VLDL composition and LDL plasma concentrations changed towards the values of the controls. In six alcoholic subjects who volunteered for LDL kinetic studies the fractional catabolic rate for LDL particles isolated immediately after the drinking period and seven days later were the same. These studies suggest that the alterations in all the apoB containing lipoproteins may contribute to the delayed progression of atherosclerosis observed in alcohol users. PMID- 1930938 TI - Aetiology of insulin-dependent diabetes mellitus--a cornucopia for research? PMID- 1930939 TI - The changing face of the epidemiology of insulin-dependent diabetes mellitus (IDDM): research designs and models of disease causation. AB - Epidemiology can be broadly defined as the study of the cause and distribution of diseases in human populations. This review is concerned with the role of epidemiology in elucidating the cause of insulin-dependent diabetes mellitus (IDDM). Methodological aspects of epidemiologic studies are discussed including study designs and their limitations. Markers of genetic susceptibility to IDDM are examined in terms of their potential value for selecting high risk individuals for prospective follow-up studies of IDDM etiology. Models of disease causation pertinent to IDDM are presented with a primary focus on the recently developed epigenesis theory. Finally, a framework is provided that integrates approaches of infectious disease, chronic disease and genetic epidemiology, to link epidemiologic data with information from other disciplines, such as genetics, microbiology or immunology. PMID- 1930940 TI - The role of genetic predisposition to type I (insulin-dependent) diabetes mellitus. AB - The aetiology of insulin-dependent diabetes (IDDM) involves genetic predisposition, a major component of which has been mapped in the HLA complex, near to or identical with genes encoding class II molecules. In Caucasian populations IDDM is strongly associated with the serologically defined HLA-DR3 and DR4 antigens, which are widely recognised as markers of susceptibility. The particularly high risk of DR3/DR4 heterozygotes suggests that susceptibility is determined by two genes acting synergistically. The development of recombinant DNA technology has allowed a finer description of the class II region and provided evidence that DQ rather than DR determinants may primarily influence IDDM susceptibility. The search for specific structural changes of the DQA and DQB genes has shown that susceptibility correlates with the absence of aspartic acid at position 57 on the DQ beta chain (DQ beta 57 Asp--) and/or the presence of arginine at position 52 on the DQ alpha chain (DQ alpha 52 Arg+). In Caucasians the formation of a putative DQ susceptibility molecule (DQ alpha 52 Arg+, DQ beta 57 Asp-) accounts best for the disease associations when transcomplementation molecules consisting of DQ alpha and beta chains encoded by different haplotypes are postulated to explain the excess risk of heterozygotes. The HLA-IDDM associations in the Japanese, however, are not explained by this model. These and other unresolved questions indicate that other residues of the DQ alpha and beta chains or other class II molecules (DR beta chains), as well as non-MHC genes, may also contribute to the susceptibility. PMID- 1930941 TI - Role of viruses in the pathogenesis of IDDM. AB - Insulin-dependent diabetes mellitus (IDDM), also known as type I diabetes, results from the destruction of pancreatic beta cells. During the past few decades, genetic factors, autoimmunity and viral infections have been extensively studied as the possible cause of beta cell destruction. The evidence for virus induced diabetes comes largely from experiments in animals, but several studies in humans also point to viruses as a trigger of this disease in some cases. There are at least two possible mechanisms for the involvement of viruses in the pathogenesis of IDDM: (a) cytolytic infection of beta cells may result in destruction of the cells without the induction of autoimmunity, or may be a final insult leading to the clinical onset of diabetes in individuals with an already decreased beta cell mass resulting from an autoimmune process; and (b) persistent viral infection (e.g. retrovirus, rubella virus, cytomegalovirus) may result in the triggering of autoimmune IDDM in certain circumstances. Regarding the latter possibility, viruses may insert, expose, or alter antigens in the plasma membrane of the beta cell, which may initiate autoimmunity leading to the destruction of the cells. PMID- 1930942 TI - Novel considerations on the antibody/autoantigen system in type I (insulin dependent) diabetes mellitus. AB - Insulin dependent diabetes (IDDM) has an autoimmune pathogenesis. Included is the presence of antibodies to pancreatic islet cells. The first identified were islet cell antibodies (ICA), detected by indirect immunofluorescence, and which react with all cells within islets. Importantly, the autoantibodies are found several years prior to disease and although a pathogenic role for the autoantibodies is unclear, they have become useful markers of prediabetes. A number of studies of twins discordant for IDDM and of first degree relatives of IDDM patients have established that there is an increased risk for disease in individuals who have ICA, especially when ICA levels are high. This high predictive value of ICA decreases in the general population where the incidence of IDDM is lower than in first degree relatives, and both ICA and the disease risk associated with ICA, appear to be influenced by a genetic susceptibility. This has been sustained in a study of patients with endocrine autoimmunity and ICA (Polyendocrine Study) where the predictive value of very high levels of ICA is less than 50% in patients without a first degree relative with IDDM. Hence, there remain a substantial number of patients with ICA who do not develop disease. From these patients, it was demonstrated that ICA include at least two distinct specificities, one of which is beta cell specific and is not associated with a high risk for IDDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930944 TI - Individuals with mental retardation in residential facilities: findings from the 1987 National Medical Expenditure Survey. AB - Data from the 1987 National Medical Expenditure Survey, a large survey designed to yield national estimates pertaining to the use of medical care, were used to compare residents of state institutions with residents of other types of residential facilities. Findings concur with past studies: Residents of state institutions were more severely retarded and more likely to have other disabilities and functional impairments than were residents of other residential facilities. However, many residents of other facilities had severe impairments. Relatively more persons with severe impairments resided in these facilities in states where small facility beds were relatively plentiful. PMID- 1930943 TI - The interface between epidemiology and molecular biology in the search for the causes of insulin-dependent diabetes mellitus. AB - Epidemiological techniques have been utilized to accumulate new knowledge about insulin-dependent diabetes mellitus (IDDM), leading to important insights into the disease process and the alteration of these mechanisms when viewed from a geographic or population base. More recently, highly powerful and sophisticated techniques of molecular biology have been added to the research arsenal, extending the knowledge on the genetic basis for IDDM and the probable environmental factors involved. The development and growth of the new discipline of epidemiological genetics promises exciting new developments for the future of our field as well as that of other major medical problems having a genetic base, but significantly influenced by environmental factors. This review stresses the importance of carefully validated diabetes registries in the study of the epidemiology of IDDM. The Children's Hospital of Pittsburgh and the University of Pittsburgh Medical Center have spear-headed the development of such registries, worldwide. The first international meeting on IDDM epidemiology in 1983 gave as a result, i.e., the finding that there were truly remarkable differences in the risk of developing IDDM depending upon the geographic location of the individual. Later collaborative work via the Diabetes Epidemiology Research International (DERI) group has confirmed the previous finding and added the description of secular trends and epidemics of IDDM. It is remarkable that the incidence rate of IDDM in children below 15 years vary from 1/100,000/yr in the Orient to 35/100,000/yr in Finland. The epidemiological approach in the study of IDDM has also stimulated research into the various facets of the etiology of the disease, genetic factors, autoimmune mechanisms and environmental factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930945 TI - Prevalence of psychoactive drug use among North Dakota group home residents. AB - To determine the prevalence of psychoactive medication usage among persons with mental retardation residing in community settings in the state of North Dakota, we sent a questionnaire to all group homes serving persons with developmental disabilities. The return rate was 97%. Psychoactive medications were used by 37% of residents represented. Results were discussed in relation to previous studies that have primarily involved institutionalized populations. PMID- 1930946 TI - Effects of parent training on families of children with mental retardation: increased burden or generalized benefit? AB - Parents of children with mental retardation have become increasingly involved in special education, including training programs to facilitate teaching at home. Although some writers have argued that families accrue generalized psychological benefits of such participation, others have cautioned that the result may be increasing the burden of child-rearing. Forty-nine families of children with mental retardation were assessed before and after a parent training program, on a variety of parent, marital, and family measures. Parents reported high satisfaction with the program and showed small but statistically significant decreases in reports of symptoms of depression, parent and family problems, overall family stress, and dissatisfaction with the family's adaptability. Family characteristics were also predictive of teaching at home one year following training. The families that reported doing the least productive teaching had entered training reporting greater child-related stress and lower satisfaction with the marriage and the family. PMID- 1930947 TI - Relation between receptive language and cognitive maturity in persons with mental retardation. AB - We examined the correlations between receptive language level and performance on indices of nonverbal cognitive functioning for 20 persons with mental retardation and for 20 children without mental retardation matched to them on nonverbal MA. The correlations suggested that the retarded group focused on the formal, sequential properties of language. The correlations also suggested that the nondisabled group placed less emphasis on the formal, sequential properties of language and more on semantic, conceptual properties. These differences in approach may explain why the persons with mental retardation did poorly on the task of understanding spoken language compared to the children without mental retardation. PMID- 1930948 TI - Contingent provision of social referential information by parents of children with and without developmental delays. AB - Social referencing involves using information from other persons to guide behavior and affect in ambiguous situations. Children's behavior toward a stimulus paired with positive affective messages was compared to behavior toward a stimulus paired with fearful messages. Normally developing children, but not those with delays, showed evidence of behavior regulation, touching positive message more than fearful-message toys. Parental communications were more regularly preceded by children's looks in dyads with normally developing children. Parents of children with delays often initiated unsolicited communications in addition to responding to children's initiations. Children with delays regulated behavior only when messages were contingent upon looks. Parental contingency was not associated with behavior regulation in dyads with normally developing children. PMID- 1930949 TI - Evaluation of the journals of the American Association on Mental Retardation. AB - Perceptions of members of the American Association on Mental Retardation (AAMR) regarding the extent to which the organization's journals, the American Journal on Mental Retardation (AJMR) and Mental Retardation (MR) assist its members in adding to their knowledge and in carrying out their professional responsibilities were obtained. The 3-page survey was mailed with AAMR membership dues renewal notices for 1988. Surveys were returned by 1,619 members, 24.8% of the paid membership as of May 1988. Survey data were analyzed on the basis of division membership and occupational category for both journals. PMID- 1930950 TI - Cross-validation of the factor structure of the Aberrant Behavior Checklist for persons with mental retardation. AB - The original factor structure of the Aberrant Behavior Checklist was cross validated with an American sample of 470 persons with moderate to profound mental retardation, including nonambulatory individuals. The results of the factor analysis with varimax rotation essentially replicated previous findings, suggesting that the original five factors (Irritability, Lethargy, Stereotypic Behavior, Hyperactivity, and Inappropriate Speech) could be cross-validated by factor loadings of individual items. The original five scales continue to show high internal consistency. These factors are easily interpretable and should continue to provide valuable research and clinical information. PMID- 1930951 TI - A principal components analysis of the Comprehensive Test of Adaptive Behavior. AB - The Comprehensive Test of Adaptive Behavior (CTAB) yields indices of functioning in six categories (Self-Help Skills, Home Living Skills, Independent Living Skills, Social Skills, Sensory and Motor Skills, and Language Concepts and Academic-Skills) and a composite Total Score. A single factor, extracted through principal components analysis of standardization sample data, accounted for approximately 86% of the variance in the six category scores, portraying the CTAB as unidimensional rather than multidimensional. Therefore, rather than use of category scores, cautious interpretation of idiographic item clusters and the Total Score may be the most psychometrically sound procedure for evaluating CTAB results. PMID- 1930952 TI - Properly characterizing clusters of families who have children with mental retardation: a comment on Mink, Blacher, and Nihira. PMID- 1930953 TI - Reaction to Zigler, Hodapp, and Edison (1990). PMID- 1930954 TI - Control of incidental asbestos exposure at hazardous waste sites. AB - This paper discusses asbestos regulations that are not part of Superfund and examines how these regulations can help to identify, evaluate and manage the risk associated with Asbestos Containing Material (ACM) at hazardous waste cleanup sites. Unless one knows where to look for ACM at hazardous waste sites, it may go undetected even after all the traditional sampling is done. Although EPA is currently developing a policy for evaluating risk from asbestos exposure at certain Superfund sites, information from existing regulations can be used to manage hazards associated with asbestos exposure at hazardous waste sites. This paper also identifies where to find governmental agency personnel and consultants who may be retained for site-specific help. PMID- 1930955 TI - Proactive industrial strategies for the Clean Air Act Amendments of 1990. AB - The Clean Air Act (CAA) Amendments of 1990 was signed into law by President Bush on November 15, 1990. These amendments potentially will have a major impact on virtually every industrial and many commercial facilities throughout the country. The regulations developed to implement this legislation will encompass new approaches to nonattainment, air toxics, accidental releases, acid rain, permits and enforcement. Because of the impact of this legislation the regulations will be implemented over a ten-year period. This paper is an overview of the amendments and recommended proactive strategies for industry. PMID- 1930956 TI - Rethinking the ozone standard. AB - Six properties appear desirable for any set of ozone attainment criteria: (1) sufficient stringency to protect public health, (2) simplicity and understandability, (3) sensitivity to real changes in air quality, (4) stability against meteorological fluctuations, (5) use of as much data as possible, and (6) equivalence between the stringency the criteria appear to mandate, and what they actually mandate. We consider how the federal attainment criteria might be improved with respect to Properties 4 through 6 while being equally strong on 1 through 3. Whether the federal standard meets Property 1 has been the subject of debate, but our analysis would apply also to a modified standard. We show that there are subtleties in how improvements might be made. In particular, basing the attainment status on a statistic with low variance may not lead to a more stable criterion, and although it is easy to find a criterion that makes it hard for a district with bad air to reach attainment, or a district with good air to get out of attainment, it is hard to find a criterion that does both. This suggests using different criteria for districts that are out of attainment from districts that are in attainment. Initially the burden of proof would be on the district to prove that its air is of attainment quality. However, once the district has achieved attainment the burden of proof would shift; the district would remain in attainment unless there was strong evidence to the contrary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1930957 TI - Relationship between self-reported activity levels and actual heart rates in teenagers. AB - A study was designed to explore the relationship between self-reported activity levels and actual heart rate (HR) as measured by a portable heart rate monitor (Sport Tester PE3000). Twenty-two teenagers (8 boys, 14 girls, median age of 16) from Watertown High School, Massachusetts participated in this pilot study which involved continuous monitoring of HR during normal daily activities and simultaneous completion of a time/activity diary. There were 31 successful monitoring sessions ranging from 1.9 to 17 hours with a median monitoring time of 12.6 hours. Four unsuccessful monitoring sessions were experienced due to equipment failure. Apart from participant cooperation, the single most important factor affecting the feasibility of continuous heart rate monitoring was found to be equipment design. The overall average heart rate observed was 88.4 bpm (SD = 24.3). An individual's correlation coefficient for perceived activity level (documented in half-hour intervals) and heart rate (averaged over the half-hour intervals) varied from 0.24 to 0.89. More than half of the correlation coefficients were below 0.40. There was a significant difference (P less than .0001) between average heart rate for time spent indoors (90 bpm) versus outdoors (103 bpm) even after correcting for sleeping time. It is concluded that continuous HR monitoring with simultaneous completion of a time/activity diary is feasible and is a promising source of information for studies on exposure to air pollutants. PMID- 1930958 TI - An equilibrium analysis of some chlorinated hydrocarbons in stoichiometric to fuel-rich post-flame combustion environments. AB - The equilibrium composition of product gases from the combustion of chlorinated hydrocarbons (CHC) has been studied for varying ratios of C, H, Cl, and O under stoichiometric to fuel-rich conditions. An interactive, PC-compatible FORTRAN program, STANJAN, was utilized in conjunction with thermochemical data sources to calculate equilibrium compositions of gas mixtures as a function of temperature. The predicted results, when judiciously interpreted, assist in the understanding of the potential for formation of residual organic substance emissions (ROSEs) in post-flame environments of an incinerator. Arguments are presented for the potential formation of chlorinated species, which are stable at ambient temperature, if locally fuel-rich mixtures penetrate into the lower temperature zones of an incinerator. ROSEs that have been observed in field tests of incinerators burning chlorinated compounds are predicted to form under the fuel rich condition. Furthermore, when the equivalence ratio is greater than unity by even a slight amount, the degree of chlorination of product gases increases markedly when the Cl/H ratio also exceeds unity. In that case, time, temperature, turbulence and an overall fuel-lean stoichiometry may not be sufficient to guarantee elimination of measurable levels of chlorinated products. Possible implications of the equilibrium calculations are discussed. Further systematic studies with additional CHCs, nitrogen-, sulfur-, and heavy metal-bearing compounds are recommended as well as continued efforts to carry out kinetic studies. PMID- 1930959 TI - Indoor-outdoor nitric oxide and nitrogen dioxide concentrations at three sites in Riyadh, Saudi Arabia. PMID- 1930960 TI - Leukaemia and anaemia in AKR/O mice I. Leukaemia characteristics, haematological variables and erythropoiesis stimulating factor(s). AB - AKR/O mice were used as a model for studying the pathogenesis of the anaemia accompanying leukaemia/lymphoma. The leukaemia incidence was 87%. Median age at diagnosis was 11.3 months. At diagnosis most of the mice had normal leukocyte counts. Clinically the mice divided into subgroups depending on the relative organ involvement: 1) thymoma group (n = 98), 2) spleen group (n = 144), 3) combined group (n = 27) and 4) mice with moderate organ changes (n = 216). Mice of group 1 were younger than the others, had a rapidly progressive disease, normal to elevated packed cell volume (PCV), and plasma erythropoietin (Epo) was normal or increased. Mice of group 2 were usually anaemic with high plasma Epo estimates and often elevated reticulocyte counts. Group 4 was the oldest group. Some of these mice were severely affected haematologically. Overall there was an inverse relation between PCV and plasma Epo estimate, indicating a normal Epo response to anaemia. In all groups increasing spleen size was associated with increased severity of anaemia and increased reticulocyte counts. The association between anaemia, elevated reticulocyte counts and spleen enlargement suggests haemolysis as a mechanism for anaemia, and also raises the question of compensatory spleen erythropoiesis. PMID- 1930961 TI - The antibacterial activity of a siderophore. 2. The influence of deferoxamine alone and combined with ascorbic acid on the activity of antibiotics against Staphylococcus aureus. AB - The in vitro activity of deferoxamine (DFO) combined with cephalothin, gentamicin, cefotaxime, vancomycin, and fusidic acid, in the presence or absence of the reductant ascorbic acid (AA) was investigated against Staphylococcus aureus by a macrobroth dilution technique and killing curve kinetics. DFO and in particular DFO + AA lowered the MICs of cephalothin, gentamicin, cefotaxime, and fusidic acid for most of the strains and in some instances also the MICs of vancomycin. To characterize the interaction between DFO or DFO + AA and antimicrobials we applied the growth constants of logarithmic growth phase. Generally DFO acted synergistically with cephalothin, gentamicin, vancomycin, and fusidic acid, particularly in the presence of AA, and in some cases synergy was demonstrated with cefotaxime, too. PMID- 1930962 TI - Comparison of 30 microgram and 120 microgram gentamicin disks for the prediction of gentamicin resistance in Enterococcus faecalis. AB - Single strain regression analysis was performed on PDM II medium for E. faecalis with 10, 30 and 120 micrograms gentamicin disks using E. faecalis, strain ATCC 29212 as the reference. This method permits the calculation of zone diameters corresponding to different MIC values for different disk contents. The lack of discrimination between normal low-level resistant strains and high-level resistance using the 10 micrograms disk was confirmed. However, both the 30 micrograms and 120 micrograms disks seemed to provide a separation of the normal low-level gentamicin-resistant population from strains with increased resistance. Since the 30 micrograms disk is used routinely in some countries, there should be no need for an extra high content disk in these laboratories. This was confirmed when 96 clinical isolates of E. faecalis were analysed and the results of routine disk diffusion tests were compared with the MIC values. Two of the strains showed high-level gentamicin resistance (greater than 2000 mg/l) and produced no zone of inhibition. The other 94 isolates showed gentamicin MIC values between 4-16 mg/l, and 72 of the MIC results were 8 mg/l. The zone diameters for these strains ranged between 15 and 25 mm with a mean of 18.2 and a median value of 18 mm. In order to include statistical considerations of the zone size populations for setting of breakpoints, a study of gentamicin zone size distributions was performed for several bacterial species. Inhibition zone diameter values around the 30 micrograms gentamicin disk for 2079 clinical isolates of E. faecalis, 2268 S. aureus, 3201 E. coli and 547 strains of P. mirabilis from different years were plotted as histograms. Tests for agreement with a Gaussian distribution showed that the histograms were slightly peaked and skewed towards higher zone values. Parametric and non-parametric statistical tests were compared and the results showed that means and medians were very similar and that parametric fractile estimations at the lower end of the histogram populations were conservative and could be used in view of a slightly lower rate of false resistance. The 1% parametric fractile of 12 mm was selected as a suitable breakpoint for the identification of normal, low-level resistant isolates of E. faecalis using the standardized disk test of the Swedish Reference Group for Antibiotics. PMID- 1930963 TI - Cell proliferation rate and tumor volume in human osteosarcoma during exposure to methotrexate. A study on tissue transplants in nude mice. AB - The growth inhibitory effect of methotrexate (MTX) on osteosarcoma cells was studied in dysthymic nude mice bearing tumor transplants obtained from a patient before (PRE-CHEM) and after (POST-CHEM) preoperative chemotherapy for osteosarcoma of the distal femur. Cell proliferation was analyzed by autoradiographic evaluation of the fraction of labeled cells after continuous administration of 3H-thymidine for seven days. Histomorphometric analysis of the tissue distribution of cells in the partly ossified tumors was performed. The PRE CHEM sarcoma transplants showed a significant reduction of labeled interphases from 52 to 1.7 percent upon daily MTX treatment of the mice as compared to controls. In contrast, MTX treatment did not inhibit cell proliferation in the POST-CHEM tumor transplants in which approximately 70 percent of the cells were labeled. Tumor volume increased by 65 and 54 percent in the MTX-treated PRE- and POST-CHEM groups, respectively. During the same eight-day period, control transplant volume increased by 30 percent (PRE-CHEM) and 20 percent (POST-CHEM). Tumor cell densities in the MTX-treated groups were reduced by a factor of approximately 11 in the PRE-CHEM transplants and by a factor of approximately 1.5 in the POST-CHEM transplants. The results show that in this patient the osteosarcoma cells had changed their responsiveness to MTX during the preoperative chemotherapy period. In both the MTX-sensitive and non-sensitive tumor lines, exposure to MTX induced increased tumor volume by increasing the extra cellular matrix volume, irrespective of the neoplastic cell proliferation rate. This effect of MTX was most pronounced in the MTX-sensitive tumor line. These results indicate that in the clinical situation it is difficult to judge the response to chemotherapy even from morphologic parameters. PMID- 1930964 TI - Synergy and cumulated killing effect of the penems FCE 22101 and FCE 25199 in combination with gentamicin against bacteria isolated from septicaemia. AB - Blood isolates of Enterococcus faecalis, Streptococcus sanguis, Staphylococcus aureus, E. coli and Klebsiella oxytoca were tested for their synergistic and cumulated killing effect (CKE) with the new penems FCE 22101 or FCE 25199 in combination with gentamicin. The tissue cage model in rabbits was used to study the CKE in vivo after antibiotic treatment of the bacteria in vitro. Synergy was observed within two to seven h with all isolates in early logarithmic phase, except with S. aureus, which was rapidly killed by the penems alone. After one h treatment with the antibiotic combinations in vitro, a CKE was demonstrated for up to six h both in vitro and in vivo. The magnitude of the CKE differed between strains and in vitro vs. in vivo. PMID- 1930965 TI - Morphology of Pseudomonas aeruginosa phages from the sputum of cystic fibrosis patients and from the phage typing set. An electron microscopy study. AB - Sixteen phage suspensions isolated from the sputum of sixteen cystic fibrosis patients and five phages from the present phage typing set were studied by electron microscopy. All sputum samples contained at least one type of bacteriophage (range: 1-4) which could be classified by the morphology and dimensions of the virion. All phages isolated from sputum as well as the four typing phages were tailed phages. The clinical phages belonged either to the Myoviridae, Siphoviridae or Podoviridae family. The four typing phages belonged to the Myoviridae family. The detection of the presence of tailed phages in sputum further supports the prevailing theory that phages play a role in the phenotypical change of Pseudomonas aeruginosa during the chronic lung infection of cystic fibrosis patients, since only tailed phages are known to be temporate and thus mediate transduction and conversion. PMID- 1930966 TI - Expression of blood group-related carbohydrate antigens in normal human pancreatic tissue. AB - The expression of type 1, 2 and 3 chain carbohydrate structures in 15 normal pancreata was investigated by immunohistochemical methods using well-defined monoclonal antibodies. Surgical biopsies of pancreata were obtained from kidney donors while the organs were still perfused. Type 1 chain structures were abundantly expressed including monosialylated(ms)- and disialylated(ds)-Le(a) antigens, which have previously been associated with cancer. Type 2 chain structures were represented by H and Le(y) antigens and to a lesser extent by the precursor structure N-acetyllactosamine, whereas Le(x), dimeric Le(x), and ms Le(x) were only sporadically observed, in contrast to fetal pancreatic tissue, in which Le(x) has been found to be abundantly expressed. H chain 3 antigen was found in nearly all specimens, whereas precursor structures Tn, sial-Tn and T antigens were absent. Desialylation unmasked the T antigen in all specimens. Absence/masking of Tn, T and related antigens is of special interest, since these antigens are associated with tumor development in other tissues, and may be of importance in pancreatic cancer diagnostics in the future. PMID- 1930967 TI - A freeze-fracture study of the perineurium in normal and protein-deprived rats. AB - Observations have been made using the freeze-fracture replication technique on the perineurium of normal and protein-deprived rats in which its permeability barrier function is known to be deficient. The perineurial cells of young normal rats possessed belt-like tight junctions (zonulae occludentes) at the borders and maculae occludentes at sites remote from their borders. In older rats, the zonulae occludentes were more prominent and the maculae occludentes relatively less frequent. No abnormalities were detected in the tight junctions of young rats with early induction of protein deficiency but this may have been related to sampling problems. In older severely protein-deficient animals, although many of the tight junctions were normal, some were abnormal and contained focal regions of dispersed strands. The density of caveolae in the surface membrane of the perineurial cells of older rats with severe protein deficiency was significantly greater than in the control animals. This provides support for the view that the pinocytotic-like vesicles of perineurial cells are involved in transport of substances across the cells. The increased numbers of caveolae in the protein deficient rats may reflect increased transcellular traffic. There were considerable differences in the density of P-face IMPs between the different perineurial lamellae, but the results did not allow a decision to be made as to whether there was a polarization of the cells between their endoneurial and epineurial aspects. No differences were detected in the density of P-face IMPs between the young control and protein-deprived rats. In the perineurium of the older rats with protein deficiency, IMP density was significantly greater in the E face than in the controls but not different in the P face. The delay in the development of enzymatic activity in the perineurium of protein-deficient rats that has been demonstrated histochemically is therefore not paralleled by a reduction in IMPs. PMID- 1930968 TI - Characteristics of spontaneously agglutinating Proteus mirabilis strains from bacteriuric patients. AB - Out of 210 Proteus mirabilis isolates from bacteriuric patients a total of eight spontaneously agglutinating strains were found. SDS-PAGE analysis of their lipopolysaccharides (LPS), the separation of polysaccharide fractions (PS) by gel filtration, and chemical characterization of PSs were performed. Out of the eight strains one S form and one mutant classified as Rc were detected. The remaining six strains were recognized as Ra and intermediate forms. When tested in a hematogenous infection model in mice, the P. mirabilis Rc mutant survived in kidneys for at least two weeks, while the Re mutant used as control was eliminated within 20 h after the challenge. These data indicated that strains of P. mirabilis may be pathogenic even if they express very incomplete LPS. PMID- 1930969 TI - Evaluation of a direct fluorescent antibody test for detection of Chlamydia trachomatis in endocervical specimens. Brief report. AB - A total of 160 endocervical specimens collected from 72 symptomatic and 82 asymptomatic women attending a gynecology outpatient clinic were investigated for genital Chlamydia trachomatis infection by the use of tissue culture and DFA test. The infection rate was 42% for symptomatic and 23% for asymptomatic patient groups. The sensitivity rates of the DFA test in the symptomatic and asymptomatic groups were 84% and 75%, while the specificity rates were 89% and 95%, respectively. The DFA test had an overall sensitivity of 80% and specificity of 93%. There was 90% agreement between the two techniques. Therefore, DFA is recommended as an alternative to tissue culture where laboratory facilities are limited and genital chlamydial infections are highly prevalent. PMID- 1930970 TI - [Diet and health behaviour in Danish children aged 11-15 years]. AB - A total of 1,671 school children aged 11, 13 and 15 years answered a questionnaire on diet, other health behaviour, social background, social network, health and life satisfaction. The proportions who ate fruit, vegetables, and rye bread every day were 77%, 64% and 94%. Moreover, 78% had fibre-containing breakfast every day and 79% had a regular lunch meal every day. 26% of the children received an optimal diet containing all of these five components every day, and 19% received less than three of these components every day. The proportions who consumed five unhealthy diet components every day (candy, chips, French fries, sausages/hamburgers, and sweet long-drinks) were 32%, 12%, 5%, 5% and 18%. 39% received at least one of these unhealthy diet components every day. There was no association between intake of healthy and intake of unhealthy diet components. We found no age differences among boys regarding the healthy diet components but an increasing consumption of unhealthy components with increasing age. Among girls we found a decreasing consumption of both healthy and unhealthy components with increasing age. Healthy diet was associated with high social class, good health, positive life satisfaction, positive school assimilation, and positive health behaviour. PMID- 1930971 TI - Selective delayed alternation deficits in dominantly inherited olivopontocerebellar atrophy. AB - In order to characterize more completely the nature of the frontal lobe-type cognitive changes in patients with dominantly inherited olivopontocerebellar atrophy (OPCA) we administered two tasks sensitive to frontal system dysfunction, delayed alternation (DA) and delayed response (DR), to 12 patients from one OPCA family. Affected members from this family have previously been shown to have a marked and widespread cerebral (including frontal) cortical cholinergic reduction as severe as that observed in Alzheimer's disease. Performance on DA, but not on DR, was significantly impaired in the OPCA patients compared to that in the controls. We suggest that the DA deficits in OPCA could be a consequence of a loss of cholinergic innervation to orbitofrontal or possibly temporal cortical areas and/or damage to the integrity of the cerebello-frontal neuronal connections. PMID- 1930972 TI - The relationship between buccofacial and limb apraxia. AB - There are at least two possible models depicting the relationship between buccofacial and limb apraxia. First, apraxia can be viewed as a unitary motor disorder which transcends the output modalities of both buccofacial and limb output. A high degree of similarity between the two types of apraxia would support this model. Alternatively, the relationship between buccofacial and limb apraxia may not include a unitary mechanism. The presence of quantitative and qualitative differences between buccofacial and limb performance would support this nonunitary model. The results of the present study support the nonunitary model. PMID- 1930973 TI - The Venus of Milo and the dawn of facial asymmetry research. AB - The dawn of facial asymmetry research dates back to the second half of the last century and started with a discussion about the asymmetry of the face of the Venus of Milo. These early observations revealed some of the lateralized patterns of the two facial halves of which we are now aware. Since these studies have up until now been completely neglected, the present review tries to provide the forgotten beginning of this avenue of lateralization research. PMID- 1930974 TI - Hemispheric asymmetries in visual pattern processing in infancy. AB - A right hemisphere advantage was observed in a previous study of 4- to 9-month old infants presented with a face discrimination task (de Schonen & Mathivet, 1990). The present study was designed to investigate pattern processing by the two hemispheres and the interhemispheric communication of this processing. Infants aged 4 to 9 months were tested with divided visual field presentations in one or two discrimination tasks. Under both task conditions, the infants had to discriminate between two patterns in which only two local components differed. Under one condition the components of the patterns were arranged so as to produce a face-like pattern. Under the other condition the same components were arranged into arbitrary patterns that were not "good form" patterns. No performance asymmetry was observed with the arbitrary patterns; whereas, a right hemisphere (RH) disadvantage was observed with the face-like patterns compared with both the RH performances on the arbitary patterns and the left hemisphere (LH) performances on the face-like patterns. These results show that the RH advantage for individual face recognition is not due to a general immaturity or inability of the LH in pattern processing at this period of development, nor to a more specific inability in a local mode of pattern processing. On the other hand, the RH does not completely lack local processing capacity, but is at a disadvantage when this local mode of processing has to be used with face-like (or good form) patterns. The interhemispheric communication of visual discrimination learning was tested by measuring learning transfer between the visual fields. Contrary to de Schonen and Bry's study (1987) on faceness recognition, no data in favor of interhemispheric communication were recorded in the present study. PMID- 1930975 TI - The effects of voluntary lateral orienting on positive manifold for lateralized cognitive tasks. AB - As an extension of previous studies (Urbanczyk, Angel, & Kennelly, Brain and Cognition, 8, 206-226) examining the effects of unimanual tapping on lateralized cognitive tasks, lateral body orienting was added to an established dual task paradigm to generate differential hemispheric activation and shifts of attention. One hundred twenty right-handed university students retained sequences of digits or spatial locations for 20 sec either alone or during finger tapping. By turning head and eyes left or right, the hemisphere congruent with the sequences (LH for digits, RH for locations) or incongruent (vice versa) was activated. Activation had little effect on retention means but greatly affected resource composition, supporting task performance. Congruent orientation produced significantly higher positive correlations between digit and location tasks than incongruent orientation. Females showed higher sequence retention correlations than males across both orienting groups. For females, congruent activation enhanced tapping rates and tapping-retention task correlations. For males, activation affected neither of these. These results suggest that congruent attentional orienting may couple or integrate regions of the less activated hemisphere into networks of the more activated hemisphere. Greater inter- and intrahemispheric connectivity in the female cortex may produce a greater dependence upon a general attentional "resource." PMID- 1930976 TI - Clinical syndromes are not God's gift to cognitive neuropsychology: a reply to a rebuttal to an answer to a response to the case against syndrome-based research. AB - In this paper we consider several issues about single-patient versus syndrome based research in response to E. Zurif, D. Swinney, and J. A. Fodor's (1991, Brain and Cognition, 16, 198-210) criticism of A. Caramazza and W. Badecker (1989, Brain and Cognition, 10, 256-295). We argue that these authors have failed to provide convincing arguments in favor of syndrome-based research. In particular, we show that the specific example--a study by D. Swinney, E. Zurif, and J. Nicol (1989, Journal of Cognitive Neurosciences, 1, 25-37)--given by these authors as a demonstration of the usefulness of syndrome-based research to inform theories of normal language processing does not in fact serve this purpose. PMID- 1930977 TI - Hair whorl and handedness. PMID- 1930978 TI - Scanning electron microscopy of hair cells, stereocilia and cross-linkage systems in experimentally induced endolymphatic hydrops. AB - In this study scanning electron microscopy was used to examine the stereocilia and their cross-linkages in guinea pig cochleas 1, 2, 4 and 8 months after endolymphatic sac obliteration. Initial changes were restricted to the stereocilia of the outer hair cells and consisted of a disarrangement and bulging of the stereocilia with an interruption of their cross-linkage systems. Subsequently, the stereocilia became fused and atrophied. Cross-linkages of inner hair cells remained intact. Loss of both outer and inner hair cells started in the apex and progressed towards the base of the cochlea. These findings indicate that early changes in the micro-architecture of the stereocilia may have a mechanical origin, with pressure fluctuations in the scala media possibly playing an important role. PMID- 1930979 TI - Cochlear permeability of neomycin and gentamicin: an immunohistochemical study. AB - Aminoglycoside antibiotics (AGAs) target specifically the cochleo-vestibular hair cells, but with varied ototoxicity. Differences in their penetration and clearance rates into the membranous labyrinth may play a role. This in turn may be related to a difference in the number of amine groups, the cationic nature, as well as the molecular weight and size of the AGA molecule. Immunohistochemical labeling techniques were used to study the pathways of gentamicin and neomycin from the perilymph into cochlear tissues and target cells. The more cochleotoxic AGA, neomycin, penetrated into cochlear tissues faster than the less cochleotoxic AGA, gentamicin. PMID- 1930980 TI - Digital image analysis of radio-opacities in the paranasal sinuses using computed radiography. AB - A computed radiograph system (Toshiba, model TCR-201) was used to investigate the digital image analysis of radio-opacity of the paranasal sinuses. The results of the preliminary phantom examination for evaluating the exposure technique indicated that the tube voltage should be kept constant. By using conventional radiographic images and tomographic images of normals and cases of sinusitis, the quantum values (Q-values), Q-value profiles, and Q-value histograms of radio opacities in the paranasal sinuses were assessed statistically. Findings demonstrated that radio-opacities in the paranasal sinuses could be evaluated quantitatively by these digital image analyses. PMID- 1930981 TI - Clip electrode method for recording eye movements in experimental animals. AB - Both the guinea pig and squirrel monkey were used in this study. An animal model for inner ear disease was established, and each animal was subjected to vestibular function tests consisting of spontaneous nystagmus recording, positional testing, caloric testing, and optokinetic stimulation testing. Recordings of nystagmus in the guinea pig and squirrel monkey were successfully obtained by using newly devised clip electrodes. A variety of nystagmic patterns in animal models following experimentally created perilymphatic fistula and labyrinthectomy are presented in this study. PMID- 1930982 TI - The effect of mastoid surgery on atelectatic ears and retraction pockets. AB - Forty children and 53 adults with a total of 111 atelectatic ears were operated on and followed up. Eight-four ears underwent tympanoplasty, while 27 ears underwent both a tympanoplasty and a mastoid operation. There were no statistically significant differences between the two operation groups as far as their age groups and the extent of the disease present. After follow-up of over 4 years, aeration of the middle ear was found to be better in the tympanoplasty group alone when compared with ears with also had mastoid operations. PMID- 1930983 TI - Experimental investigations on the influence of anemia on gentamicin ototoxicity. AB - The purpose of this study was to determine whether or not anemic patients have a higher risk of gentamicin ototoxicity. Using the laboratory rat as an animal model with auditory brain-stem response measurements and surface preparations of the organ of Corti, it could be shown that cochlear damage in anemic rats treated with gentamicin was significantly higher (P less than 0.05) than in the nonanemic ones treated with the same dosages of antibiotic. Doses of gentamicin used were 50 mg/kg for 30 days and 40 mg/kg for another 75 days. PMID- 1930984 TI - Click- and tone-burst-evoked otoacoustic emissions in normally hearing ears and in ears with high-frequency sensorineural hearing loss. AB - Otoacoustic emissions (OAEs) evoked by clicks and tone bursts (TBs) were measured using a minor modification of the 1987 Bray and Kemp system in normal and hearing impaired ears with high-frequency sensorineural hearing loss. Sixty ears of 60 subjects were tested. The average behavioral hearing threshold of 20 normally hearing ears was measured for the different "nonlinear" stimulus groups and defined as 0 dBnHL. Emissions were recorded in another 20 normally hearing ears and in 20 ears with steep high-frequency sensorineural hearing loss above 2kHz. An unfiltered click of 80 microseconds duration and TBs at frequencies of 0.5, 1, 2, 3, 4, 5, and 6 kHz served as stimuli. The ears with high-frequency hearing loss were clearly distinguished from the normal ears in that emission energy decreased with higher frequency stimuli above 2 kHz. The mean slopes of the response-growth functions were significantly higher at lower audiometric thresholds. The normal ears showed a slope of 0.21-0.35 dB/dBnHL above 2 kHz while the slope of the pathological ears was 0.04-0.13 dB/dBnHL. These differences in TBOAEs could possibly be used clinically to carry out hearing tests that are more frequency-specific than those measuring solely click-evoked OAEs. Pathological ears had emissions in the lower frequency range, where they had a normal audiometric threshold. However, these emissions had significantly far lower amplitudes at frequencies around 0.5 and 1 kHz when compared to normal ears. This reduced emission energy may indicate a cochlear impairment of the pathological ears in frequency ranges where they still had normal audiometric thresholds. PMID- 1930985 TI - Comparative acute ototoxicity of loop diuretic compounds. AB - A microelectrode was used to measure endocochlear potentials (EP) in adult chinchillas and to study the effects of a series of loop diuretics. EP was measured before, during and for several hours after the intravenous injection of the following loop diuretics: furosemide, piretanide, bumetanide, ethacrynic acid, indacrinone stereoisomers and ozolinone. The first four loop diuretics caused a substantial dose-related reduction of EP. The (-) isomer of indacrinone was found to cause a dose-related reduction of EP to a moderate degree. The (+) isomer of indacrinone and ozolinone caused very little change of EP, even in very high doses. Findings are consistent with data on the mechanism of action of these agents in the kidney. PMID- 1930986 TI - Primary culture of vital marginal cells from cochlear explants of the stria vascularis. AB - Explants of the stria vascularis and spiral ligament were dissected from guinea pig cochleae and were successfully cultivated for several weeks. After 2 days, fibroblast-like cells of the spiral ligament covered the bottom of the cell culture dish around the explant. Marginal cells of the stria vascularis proliferated and grew on the luminal surface towards the border of the explant at a rate of 15 microns/day. At day 6 in culture the proliferating marginal cells reached the border of the explant and then advanced to the bottom of the cell culture dish. There the marginal cells replaced fibroblast-like cells and built an epithelial hexagonal-shaped monolayer. Light microscopic and transmission electron microscopic investigations revealed that the cultured cells were viable and that typical morphological characteristics of marginal cells were preserved. Cultivation of these cells provides a unique model for studies of physiological properties of marginal cells of the stria vascularis. PMID- 1930987 TI - A horseradish peroxidase study of the fiber orientation in the facial nerve. AB - Horseradish peroxidase (HRP) was used to investigate the motor fiber orientation in the cat's intratemporal facial nerve. When HRP was applied to the zygomatic rami, HRP-labeled fibers were distributed diffusely throughout the labyrinthine and tympanic segments. On the other hand, distal to the chorda tympani entrance, a well-defined topographical orientation was found in the posterolateral aspect of the nerve. When HRP was applied to the buccal rami, topographical orientation was found in the posteromedial area of the distal mastoid segment. When HRP was applied to the posterior auricular rami, topographical orientation was found in the center to the anterior area of the distal mastoid segment. These results indicate that each branch of the facial motor nerve has a topographical orientation in the distal part of the mastoid segment, while nerve fibers are dispersed in the tympanic and labyrinthine segments. PMID- 1930988 TI - Immunohistopathology of variations of human olfactory mucosa. AB - The characteristics of the human olfactory mucosa were studied immunohistologically. Regular, zonal distribution of the supporting cells, multilayered olfactory receptor cells and basal cells was commonly found in the olfactory mucosa of the human fetus. In contrast, most of the olfactory mucosa in the adult varied to some extent. In the relatively thick, slightly degenerated olfactory mucosa, olfactory marker protein positive receptor cells were arranged irregularly. The most common evidence for variation was the decrease or disappearance of the olfactory receptor cells. Serous-type lactorferrin containing glandular acini were characteristically found beneath degenerated epithelium. Islands of respiratory epithelium were also seen. The ductules of the Bowman's glands were distended and the openings of these ductules were wide. There was invagination or epithelial cell processes into the glandular lumina. These findings suggest that the epithelial cells of Bowman's glands play an important role in the regeneration of the human olfactory mucosa. PMID- 1930989 TI - Immune response after collagen injection for laryngeal rehabilitation: development of an enzyme-linked immunosorbent assay. PMID- 1930990 TI - Maxillary sinusitis. PMID- 1930991 TI - The shell tamponade technique for glaucoma filtration surgery. PMID- 1930992 TI - Retinochoroidal (optociliary) shunt veins, blindness and optic atrophy: a non specific sign of chronic optic nerve compression. AB - Fifteen patients are described in whom the triad of blindness, optic disc swelling followed by optic atrophy, and optociliary shunt veins occurred. The causes of the syndrome included spheno-orbital meningioma, optic nerve glioma, meningocele of the optic nerve, and chronic papilloedema. It is postulated that chronic compression of the intraorbital portion of the optic nerve produces gradual obstruction of the central retinal vein, thus preventing the normal passage of venous blood from the retina through the central retinal vein to the cavernous sinus. Optociliary veins are a pre-existing shunt system that allows retinal venous blood to bypass the central retinal vein and exit from the orbit via the choroidal circulation and its anastomoses. PMID- 1930993 TI - Visual parameters in patients with pituitary adenoma before and after transsphenoidal surgery. AB - Eighty-two patients with pituitary adenoma who underwent transsphenoidal surgery were examined before and after surgery. Nineteen patients had a normal preoperative neuro-ophthalmological examination. All of these patients maintained normal visual parameters postoperatively. The remaining 63 patients had tumour related loss of visual acuity, visual field, or both. These patients ranged in age from 18 to 78 years. Duration of symptoms ranged from one day to ten years, with a median of six months. Preoperative visual acuity was 6/12 or better in 72% of eyes, with 90% of patients having 6/12 or better in their better eye. Only 7% of eyes had a normal preoperative visual field. Both visual acuity and visual field improved postoperatively in the majority of eyes. In eyes that were examined within one week after surgery and subsequently, substantial improvement occurred within the first postoperative week, but further improvement continued over weeks to months postoperatively, with visual field taking longer to stabilise than visual acuity. Visual acuity at last examination was 6/12 or better in 87% of eyes, and visual field at last examination was normal in 50% of eyes. A total of 92% of patients had visual acuity of 6/12 or better in their better eye, and 62% of patients had a normal visual field in their better eye. Visual acuity at last examination was correlated with both age and preoperative visual acuity. Last visual field also was correlated with both age and preoperative visual field. Patients with preoperative optic atrophy had a poorer visual prognosis than did patients with normal fundi. PMID- 1930994 TI - The effect of age and initial visual acuity on the systemic and visual prognosis of central retinal vein occlusion. AB - Papillophlebitis is the term that is often used to describe a central retinal vein occlusion with preserved visual acuity in a young, healthy patient. Among 194 patients with a diagnosis of central retinal vein occlusion (CRVO), 19 patients were identified who were under 50 years of age and who had visual acuity of 6/12 or better in the affected eye. These patients retained good vision in the affected eye during the course of the disorder with 17 eyes returning to 6/6. All of these patients remained healthy over a mean follow-up period of about four years. This group of patients was compared to a second group of 28 patients who also were under 50 years of age, but who had initial visual acuity in the affected eye less than 6/12. These patients had a variable visual outcome. In addition, they had a higher prevalence of systemic hypertension over the follow up period than did a group of age-matched control subjects. An additional comparison was made to a group of 26 patients with visual acuity of 6/12 or better in the affected eye but who were over 50 years of age. Forty-six per cent of these patients had final visual acuity less than 6/12, and they had a higher prevalence of systemic vascular disease than did a group of age-matched control subjects. PMID- 1930995 TI - Treatment of pterygia in Queensland. AB - All practising ophthalmologists in Queensland completed a written survey on their current methods of treatment of pterygia. The indications for surgical removal, in decreasing order of importance, were mainly size, symptomatic complaints, cosmetic appearance and activity. Most surgeons graded pterygia into a variety of classifications. The most common form of treatment for primary pterygia was simple excision plus mobilisation of conjunctiva and suturing conjunctival free edges together followed by bare sclera technique, and simple excision plus thiotepa drops. For recurrent pterygia simple excision plus beta-irradiation was the most common form of treatment, followed by simple excision plus thiotepa drops and simple excision plus mobilisation of conjunctiva and suturing conjunctival free edges together. A third of the ophthalmologists electively avoid cautery use during pterygium surgery, while almost a quarter of the ophthalmologists attempt to polish the corneal and limbal region. When beta radiation or Thiotepa is used there is a general consensus on the dosage for each of these. Seventeen per cent of ophthalmologists said they had not encountered any complications after pterygium surgery with the remainder quoting corneoscleral necrosis from beta-radiation and Tenon's granuloma as the most common complications. It would appear that there is no consensus on the best way to treat pterygia in Queensland, which probably reflects the lack of scientific proof for one method being superior to another. PMID- 1930996 TI - An effective method of anastomosis of the nasolacrimal canal. AB - An effective method of anastomosis of the nasolacrimal canal is summed up in data derived from 150 cases seen over 20 years at the People's Hospital of Jiangsu Province. This paper describes briefly this experience and analyses the success of this procedure. PMID- 1930997 TI - Corneal hazards in use of Simmons shell. AB - A Simmons tamponade shell was used in 10 cases of post-trabeculectomy overfiltration leading to shallow (iridocorneal touch) or flat anterior chamber. The Simmons shell was an unqualified success in only three cases. Corneal abscess (one case) and corneal abrasion/epithelial loss (four cases) necessitated premature removal of the shell. Three of the patients with corneal abrasions had a formed anterior chamber at the time of shell removal but this shallowed again within 12 hours. Two of these required surgical reformation of the anterior chamber and one reformed spontaneously. Air entrapment causing corneal dessication was probably responsible for the abrasion/epithelial loss. The patient who developed a corneal abscess was grossly malnourished. Use of the Simmons shell needs close monitoring and it should be removed at the first sign of corneal toxicity (abrasion/epithelial loss). Extreme care is necessary in malnourished cases. PMID- 1930998 TI - Papillitis, retinal neovascularisation and recurrent retinal vein occlusion in Toxoplasma retinochoroiditis: a case report with uncommon clinical signs. AB - A clinical case report, illustrative of three uncommon features of ocular toxoplasmosis, is presented. The unusual signs were recurrent retinal vein occlusion, papillitis and florid disc neovascularisation. PMID- 1930999 TI - Secondary capsulotomy. How often? PMID- 1931000 TI - Two technical aspects of the Hughes' procedure. PMID- 1931001 TI - Tendon lengthening procedures. PMID- 1931002 TI - Optic disc swelling--an important sign in neuro-ophthalmology. PMID- 1931003 TI - Pterygium surgery--time to take it seriously. PMID- 1931004 TI - Lacrimal surgery in China. PMID- 1931005 TI - The DiGeorge anomaly. AB - The DiGeorge anomaly, DGA (formerly termed DiGeorge syndrome), is now known to be a developmental field defect in which pharyngeal pouch derivatives do not arise, usually because of inadequate neural crest contributions. The conditions in which this occurs include exposure to teratogens, cytogenetic abnormalities, and Mendelian disorders. As a result, the facies and cardiovascular defects which occur are very characteristic. Two rare conotruncal anomalies, type B interrupted aortic arch and truncus arteriosus account for over half of the cardiac lesions seen in DGA. Failure of descent of the thymus is extremely common in DGA, but immunodeficiency which requires correction occurs only in approximately 25% of the cases. The term, complete DGA, should be reserved for those patients in need of reconstitution of the immune system. One can identify those patients requiring treatment of the thymic defect by T cell enumeration and in vitro proliferation assays. Two alternatives for therapy are thymus transplantation and bone marrow transplantation from a HLA matched sibling. PMID- 1931006 TI - IgA deficiency. AB - IgA deficiency, the most common primary immunodeficiency, is a very heterogeneous clinical disorder which may be associated with a variety of infections, allergies, autoimmune disorders, gastrointestinal diseases, and genetic disorders. The central phenotypic feature of this immunodeficiency is a B cell differentiation arrest, the extent of which may determine the clinical variability. Integrity of the immunoglobulin genes and their expression by immature B cells in affected individuals suggests an immunoregulatory basis for the B cell arrest. Genetic studies imply that a susceptibility gene in or near the major histocompatibility locus may predispose homozygous individuals to a spectrum of antibody deficiencies which may range from isolated IgA deficiency to panhypogammaglobulinemia. Essential cofactors in the pathogenesis of IgA deficiency include environmental factors, such as certain drugs and viral infections. PMID- 1931007 TI - Purine nucleoside phosphorylase deficiency. AB - Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disease accounting for approximately 4% of patients with severe combined immunodeficiency. Thirty-three patients have been reported. PNP-deficient patients suffer from recurrent infections, usually beginning in the first year of life. Two thirds of patients have evidence of neurologic disorders. Findings range from spasticity to developmental delay, to mental retardation. One third of patients develop autoimmune disease. The most common manifestation of this is autoimmune hemolytic anemia. Idiopathic thrombocytopenic purpura and systemic lupus erythematosis have also been reported. Patients usually present with infections but approximately one fourth have come to medical care initially for neurological problems. In PNP deficiency, T- and B-cell immunity are affected. T cell function may be profoundly deficient, may be normal at birth and then decrease with time, or may fluctuate repeatedly between low and normal. B-cell function can be normal but is deficient in approximately one third of patients. PNP protein is a trimer of approximately 90,000 daltons. It is found in most tissues of the body but is at highest levels in lymphoid tissues. This tissue distribution explains why the lymphoid system is predominantly affected in PNP deficiency. Many mechanisms have been proposed to explain the metabolic toxicity in PNP deficiency. The elevated dGTP found in PNP deficiency is thought to inhibit ribonucleotide reductase and, thus, impede cell division. Depressed GTP levels may correlate with neurologic dysfunction. The gene for PNP has been cloned; it is located on the long arm of chromosome 14. Studies of a mutant PNP gene isolated from one patient showed that a point mutation resulting in an amino acid substitution was responsible for PNP deficiency. PNP deficiency has a grave prognosis. No patient has reached the third decade of life. Twenty-nine of the 33 reported patients have died from their disease. Prenatal diagnosis is currently available. Many different therapies have been utilized for PNP deficiency including bone marrow transplantation, red cell transfusions, and supplementation of the diet with purines and pyrimidines. None of these therapies has been consistently successful. In light of the poor prognosis for PNP deficiency, bone marrow transplantation should be considered for all patients. In the future, improved forms of therapy such as gene therapy may become available. PMID- 1931008 TI - Primer design for the cloning of immunoglobulin heavy-chain leader-variable regions from mouse hybridoma cells using the PCR. AB - To facilitate the rapid cloning and sequencing of rearranged murine heavy-chain variable regions, we have designed a set of universal primers using conserved sequences of leader (signal peptide), framework one and constant regions of the immunoglobulin heavy-chain genes. RNA was extracted from the mouse hybridoma cells secreting monoclonal antibodies: IOR-T3 (anti-CD3), C6 (anti-P1 of N. meningitidis B385), IOR-T1 (anti-CD6), CB-CEA.1 (anti-carcinoembryonic antigen), CB-Fib.1 (anti-human fibrin) and CB-Hep.2 (anti-hepatitis B surface antigen). First-strand cDNA was synthesized and amplified using PCR. The primers successfully amplified correct size fragments from cDNA prepared from all hybridomas. These methods will facilitate the cloning and sequencing of mouse immunoglobulin variable regions. PMID- 1931009 TI - Rapid re-amplification of PCR products purified in low melting point agarose gels. AB - A rapid, simple method is described for performing sequential amplifications of purified products produced by the PCR. After the initial amplification, an aliquot of the reaction is run on a low melting point agarose gel. A Pasteur pipet is used to punch out a gel plug from the amplified band. The DNA in this plug is then used directly as the template for a second round of amplification. Relatively large amounts of agarose can be tolerated without noticeable effects on amplification. Use of a composite gel made from agarose and linear polyacrylamide increases the ease and utility of this technique. These gels are simple to cast, easier to handle and permit several replicate plugs to be obtained from a single band. This method is well suited to experiments which use "nested" primers to increase the sensitivity and specificity of amplification or any method in which PCR amplification follows DNA purification by electrophoresis in LMP agarose gels. PMID- 1931010 TI - Direct radioactive labeling of unpurified PCR products using Klenow fragment. AB - We describe a method for rapid radioactive labeling of PCR product. The method, employing the Klenow fragment of DNA polymerase I, consumes little product, requires no product purification and takes under 30 minutes. PMID- 1931011 TI - Detection of loss of heterozygosity in tumor DNA samples by PCR. AB - We demonstrate that PCR amplification of human genomic DNA can be used for the detection of loss of heterozygosity (LOH) in tumor samples. A 250-bp fragment containing codon 72 of the human p53 gene was amplified, ThaI digested and electrophoresed. Tumor LOH is detectable both by ethidium bromide staining and autoradiography, despite 25% contamination with normal DNA. This technique provides a fast and reproducible alternative to conventional Southern blotting and has minimal sample requirements. PMID- 1931012 TI - Detection of DNA contamination in Taq polymerase. PMID- 1931013 TI - Rapid identification of recombinant baculoviruses using PCR. PMID- 1931014 TI - PCR analysis of alternative splicing pathways: identification of artifacts generated by heteroduplex formation. PMID- 1931015 TI - Easy removal of oil from microtiter dishes following PCR. PMID- 1931016 TI - Amplification of a 9.0-kb fragment using PCR. PMID- 1931017 TI - Probing the nature of chromosomal DNA-protein contacts by in vivo footprinting. AB - Of the various approaches employed to unravel the mechanisms of gene regulation, the method of in vivo footprinting seems likely to be increasingly perceived as indispensable. A clear knowledge of the actual pattern of DNA-protein interactions occurring at a given gene within a cell, gained from data obtained with a minimum of external perturbation, can provide a benchmark against which attempts at in vitro reconstruction of the relevant interactions can be judged. This appears particularly important given our current awareness of the degeneracy displayed by certain DNA sequences in terms of their in vitro ability to separately bind to more than one (sometimes several) species of protein factor present in a nuclear extract. The mutual pursuit of both in vivo and in vitro approaches will likely provide the best route to a detailed molecular description of regulatory interactions. Following the introduction of both improved and novel technical approaches, the possibility of probing chromosomal DNA-protein associations at nucleotide resolution is now well within the capacity of most laboratories. In this article the techniques of, probing reagents used for, and some important results obtained by in vivo footprinting are critically discussed. PMID- 1931018 TI - PCR-mediated chemical mutagenesis of cloned duplex DNAs. AB - We describe an efficient, PCR-mediated protocol for random chemical mutagenesis of cloned duplex DNAs. The method involves a single molecular cloning step and is compatible with a wide variety of recombinant DNA vectors. To illustrate the procedure, we report the nitrous acid mutagenesis of a human ribosomal protein S14 cDNA fragment. PMID- 1931019 TI - Rapid restriction map constructions using a modified pWE15 cosmid vector and a robotic workstation. AB - This paper describes a number of techniques for rapid restriction mapping of cosmid clones. First, we have replaced the cloning site of cosmid vector pWE15 with a polylinker containing 15 infrequently cleaved restriction enzyme sites that are placed asymmetrically on each side of the BamHI cloning site. DNA cloned into this vector can be fully recovered by using several pairs of restriction enzymes. Second, we have designed a simple electrical circuit device that allows the performance of asymmetric voltage gradient field inversion gel electrophoresis (AFIGE) to improve the resolution of DNA molecules in the range of 20-50 kbp. AFIGE can be obtained by simply placing the device in between a commercially available switching unit and the gel box in a standard field inversion system. Finally, the restriction digestion procedure has been automated by using a Beckman Biomek 1000 robotic workstation. Using this automated system, 96 restriction reactions, including gel loading, can be performed in less than two hours. In summary, these methods represent at least a tenfold improvement in the speed and/or mapping data that can be obtained in a single gel. PMID- 1931020 TI - Preparation and characterization of immunoliposomes for targeting of antiviral agents. AB - Antibodies specific to avian myeloblastosis virus envelope glycoprotein gp80 were raised. Immunoliposomes were prepared using anti-avian myeloblastosis virus envelope glycoprotein gp80 antibody. The antibody was palmitoylated to facilitate its incorporation into lipid bilayers of liposomes. The fluorescence emission spectra of palmitoylated IgG have exhibited a shift in emission maximum from 330 to 370 nm when it was incorporated into the liposomes. At least 50% of the incorporated antibody molecules were found to be oriented towards the outside in the liposomes. The average size of the liposome was found to be 300 A, and on an average, 15 antibody molecules were shown to be present in a liposome. When adriamycin encapsulated in immunoliposomes was incubated in a medium containing serum for 72 h, about 75% of the drug was retained in liposomes. In vivo localization studies, revealed an enhanced delivery of drug encapsulated in immunoliposomes to the target tissue, as compared to free drug or drug encapsulated in free liposomes. These data suggest a possible use of the drugs encapsulated in immunoliposomes to deliver the drugs in target areas, thereby reducing side effects caused by antiviral agents. PMID- 1931021 TI - Antibody quantitation in seconds using affinity Perfusion Chromatography. AB - An extremely rapid assay technique for antibodies has been developed utilizing protein A or protein G bound to Perfusion Chromatography support matrices. Either dilute or concentrated samples are directly injected on a column that selectively binds antibody, which is quantitated directly by elution and UV absorbance. Due to the unique mass transport characteristics of the supports, total assay cycle times are typically 1 minute or less, with assays as short as 15 seconds possible. The assay system can accurately quantitate a 100,000:1 or greater dynamic range in sample concentration without sample dilution, is extremely repeatable and is easy to automate with conventional HPLC systems. Assay of antibodies in a wide range of sample types has been demonstrated. PMID- 1931022 TI - Building ruggedness into HPLC quality control procedures. AB - HPLC methods for protein and peptide analysis are excellent in terms of resolution, selectivity and recovery. They are, however, complex procedures involving multiple parameters including instrumentation, columns and mobile phases that may lead to inter- or intra-laboratory deviations. The factors that contribute to differences in retention, selectivity and sensitivity are discussed, followed by suggestions for eliminating or compensating for the differences. PMID- 1931023 TI - Matrix effects in the derivatization of amino acids with 9-fluorenylmethyl chloroformate and phenylisothiocyanate. AB - Pre-column derivatization of amino acids is widely practiced today for the HPLC analysis of amino acids. Due to the requirement for pH control, excess reagent removal and multi-step manipulations, automation is a major challenge in the derivatization of amino acids. Another challenge for pre-column chemistries is the effect of matrices in the sample such as salts, buffers and surfactants. This paper reports on automated derivatization using phenylisothiocyanate (PITC) and compares matrix effects between this PITC method and that of derivatization using 9-fluorenylmethyl chloroformate (FMOC). An autosampler was programmed to mix amino acid samples with PITC or FMOC reagent, allow a programmed reaction time, extract excess reagent and finally inject onto the HPLC. To study sample matrix effects, amino acid samples were spiked with various concentrations of Tris-HCl, phenol, citrate, sulfosalicylic acid, sodium chloride and sodium dodecyl sulfate. Using the PITC method and the FMOC method, the recoveries of amino acids in varied sample matrices were compared to pure amino acid standards. The PITC method appears to be affected less by matrix effects than the FMOC method. However, the FMOC method has a higher sensitivity so that sample dilution (up to 30 times) can be used to eliminate matrix effects. PMID- 1931024 TI - A rapid method for purifying PCR products for direct sequence analysis. AB - An HPLC approach for purification and sequencing of double-stranded DNA obtained directly from a PCR is described. This simple and reliable procedure has several advantages; the DNA fragment is rapidly eluted (less than 7 minutes), requires no organic cleanup, produces several hundred bases of sequence and is sensitive enough to obtain DNA sequence from a single 100-microliters PCR. This method is demonstrated by sequencing tumor necrosis factor alpha (TNF alpha) gene amplified from mouse tail DNA. PMID- 1931025 TI - Rapid analysis and quantitation of PCR products by high-performance liquid chromatography. AB - HPLC utilizing a high efficiency anion-exchange column provides a rapid and easily automated technique for the qualitative and quantitative analysis of subnanogram to microgram amounts of DNA fragments generated by the PCR. The accuracy, precision and linearity of this method exceed those attainable with electrophoretic techniques. In addition, because of the nondestructive nature of HPLC, the desired PCR amplification product can be purified for subsequent utilization. Thus, liquid chromatography extends the utility of the PCR technique to those applications requiring precise quantitation. PMID- 1931026 TI - A fast method for high-quality genomic DNA extraction from whole human blood. AB - A simple and fast protocol is described for the purification of genomic DNA from 0.3 ml of whole human blood. The recovery of DNA is quantitative and reproducible; the quality is such that it can be used for all relevant molecular biology techniques. PMID- 1931027 TI - Generation of recombinant baculovirus via liposome-mediated transfection. AB - Baculovirus expression vectors have become a popular method of producing recombinant proteins. Production of recombinant virus requires the transfection of both the native viral DNA and a transfer plasmid into insect cells where recombination takes place. While several methods of transfecting insect cells exist, we have found liposome-mediated transfection to be highly efficient. Here we detail the protocols and medium needed for efficient, simple transfection of Spodoptera frugiperda cells. PMID- 1931028 TI - DNA transfection in COS cells: a low-cost serum-free method compared to lipofection. AB - We describe a defined medium that allows efficient DNA transfections in COS cells and transient expression of the corresponding recombinant protein in serum-free conditions. With a modified DEAE-dextran/chloroquine method, we obtained 80% more transfected cells expressing the recombinant human interleukin-2 receptor than with transfection with cationic liposomes, one of the most efficient techniques to date. The absence of serum in the culture medium should reduce subsequent purification steps for production of recombinant mammalian proteins. Moreover, it should allow investigations dealing with the role of serum or other exogenous factors on mRNA stability or post-translation events during protein synthesis. PMID- 1931029 TI - Immunocytochemical labeling of chitin in the cell walls of zoopathogenic fungi. AB - Chitin is a complex polysaccharide composed of repeating units of beta-1,4-N acetyl-D-glucosamine. It is found in many invertebrates, in some algae, in the cyst form of several protozoans and in the cell walls of most fungi. Chitin, however, is not expressed in vertebrate tissues. We used a polyclonal rabbit antiserum against macromolecular chitin to label and stain by immunoperoxidase technique in formalin-fixed, paraffin-embedded tissues a variety of zoopathogenic fungi. The antiserum bound to the cell walls of the microorganisms, but not to (mammalian) host tissue elements. PMID- 1931030 TI - An improved method for visualizing baculovirus plaques in cell agarose overlays. PMID- 1931031 TI - Resistance to restriction digestion by plasmids prepared with a lithium containing lysis buffer. PMID- 1931032 TI - Detection of plasmid contamination in PCR samples. PMID- 1931033 TI - A simple device for collecting DNA from centrifuge tubes following EtdBr-CsCl density gradient ultracentrifugation. PMID- 1931034 TI - Rapid indirect immunofluorescence of cultured cells facilitated by microwave heating. PMID- 1931035 TI - Efficiency of biotin end-labeling of DNA fragments is rapidly tested by gel retardation with streptavidin analog. PMID- 1931036 TI - Selectable plasmid vectors with alternative and ultrasensitive histochemical marker genes. AB - Three different histochemical marker genes--E. coli beta-galactosidase gene (lacZ), Drosophila alcohol dehydrogenase gene (ADH) and human placenta alkaline phosphatase gene (ALP)--were cloned into a eukaryotic expression vector also containing the neomycin resistance gene. After calcium phosphate transfection and G418 sulfate selection of recipient BALB/c 3T3 cells, stable transfectants were pooled for histochemical staining. The lacZ-bearing cells produce aqua blue staining for beta-galactosidase; ADH-bearing cells, blue-black staining for alcohol dehydrogenase; and ALP-bearing cells, red staining for alkaline phosphatase. Cells carrying different marker genes can be easily differentiated by double-staining protocols. In addition, various photographic films can be used to enhance the colors of specific histochemically tagged cell classes. These plasmid vectors, providing selectability with the neomycin resistance gene and ultrasensitivity of alternative histochemical marker genes, will be very effective in virtually any biological system requiring analyses of multiple cell clones or classes in culture model systems or in situ. PMID- 1931037 TI - An efficient method for the extraction of DNA from formalin-fixed, paraffin embedded tissue by sonication. AB - A method was developed for fast and efficient isolation of DNA from formalin fixed, paraffin-embedded tissue sections for subsequent use in PCRs and DNA hybridization assays. The method relies on the use of a sonicating water bath to disrupt tissue samples to which a small amount of micro-sized glass beads have been added. The sonicating glass beads provide fast and efficient physical shearing of fixed tissue sections, allowing for quick release and solubilization of the DNA. The extraction process from paraffin section to amplifiable target DNA takes 30 minutes. The method eliminates the need for repetitive solvent extractions and exhaustive proteinase K digestion. PCR amplification of human genomic and viral target sequences was successfully carried out on DNA isolated from a number of different types of normal and infected tissues. PMID- 1931038 TI - Polyhedrin initiator codon altered to AUU yields unexpected fusion protein from a baculovirus vector. AB - A recombinant baculovirus expression vector was constructed to express the core (capsid) protein of the hepatitis B virus. Along with the expected 21-kDa polypeptide, a second 24-kDa protein was observed. Immunoprecipitation and immunoblotting using a rabbit polyclonal anticore antiserum demonstrated that the two proteins were related. The core gene originally was cloned in-frame with the polyhedrin initiator codon that had been altered to AUU as a means of preventing fusion protein formation. A transient expression assay revealed expression of the 24-kDa protein was prevented if a frame-shift mutation was created upstream of the HBV core translation start site. These results suggest that the 24-kDa protein was the result of an unexpectedly high level of translation initiation at the AUU codon that gave rise to a polyhedrin-HBV core fusion protein. The 24-kDa core protein was shown to be a polyhedrin fusion protein by immunoblotting with an antipolyhedrin antiserum, and initiation at the AUU was demonstrated by amino terminal protein sequencing. Methods to prevent undesired fusion protein expression using this or similar vectors are discussed. PMID- 1931039 TI - Influence of PCR parameters on amplifications of HIV-1 DNA: establishment of limiting sensitivity. AB - We have investigated the optimal reaction conditions and the limiting sensitivity for detection of HIV-1 DNA by PCR. The amplification systems studied were gag (SK38/SK39); pol (P3/P4); and two other systems described here for the first time, LTR (LTR1/LTR2) and nef (Nef1/Nef2), which amplify fragments of 115 bp, 308 bp, 632 bp and 643 bp, respectively. Two PCR profiles were assayed, and the requirements for deoxynucleoside triphosphate and MgCl2 concentrations for each amplification reaction were determined. Optimal reaction conditions were oriented toward selecting maximal amplification of the expected size fragment. Limiting sensitivity was estimated by testing the decreasing copy number of a plasmid containing HIV-1 genome and obtaining a positive amplification signal with at least 5, 5, 10 and 5 copies for LTR, gag, pol and nef, respectively. We conclude that the establishment of the detection sensitivity on a PCR is an important parameter to be considered for the interpretation of results on HIV-1 infection. PMID- 1931040 TI - Role of the extracellular matrix in tissue-specific gene expression in the sea urchin embryo. AB - The role of extracellular matrix (ECM) in the differentiation of tissue types was examined in embryos of Strongylocentrotus purpuratus. We have examined the expression of various tissue-specific molecular markers after disrupting the ECM by culturing embryos in the presence of beta-aminoproprionitrile fumarate (BAPN), which disrupts collagen deposition, and beta-D-xyloside, which disrupts proteoglycan metabolism. The markers examined included accumulation of primary mesenchyme-specific mRNA (SM 50); an aboral ectoderm-specific mRNA (Spec 1); and a gut-specific enzyme, alkaline phosphatase. Treatment with BAPN or beta-D xyloside results in developmental arrest at the mesenchyme blastula stage. Although spicule formation is inhibited, the accumulation of SM 50 transcripts and the synthesis of most of the prominent spicule matrix proteins is similar to that of control embryos. Spec 1 mRNA, in contrast, while accumulating to a significant extent when collagen and proteoglycan metabolism is disrupted, does accumulate to a level somewhat lower than that seen in control embryos. Additionally, the postgastrula rise in gut-specific alkaline phosphatase is reversibly inhibited by BAPN and xyloside treatment. These results demonstrate a differential effect of the ECM on expression of tissue-specific molecular markers. PMID- 1931041 TI - Mouse blastocysts respond metabolically to short-term stimulation by insulin and IGF-1 through the insulin receptor. AB - Insulin specifically stimulates protein synthesis in compacted mouse embryos on days 3 and 4 after fertilization, with an EC50 of 0.5 pM (Harvey and Kaye, 1988). The identity of the receptor mediating this short-term effect of insulin was further examined by dose-response studies with IFG-1 and by using a specific anti insulin receptor antiserum that has no appreciable cross-reaction with IGF-1 receptors. IGF-1 caused a maximum 40% stimulation of protein synthesis after 4 h exposure (similar to the response to insulin) with an EC50 of 150 pM IGF-1. The insulin receptor-specific antiserum, or IgGs isolated from it, also stimulated protein synthesis at dilutions as high as 1:1,000 to the same degree as insulin (approximately 40%). This agonistic action of the insulin receptor antiserum, the EC50 of 150 pM for IGF-1, and the previously established EC50 of 0.5 pM for insulin, all with similar maximal stimulation, strongly support the conclusion that the short-term metabolic stimulation of mouse blastocysts by insulin is mediated by insulin receptors. Immunosurgical isolation of inner cell masses before and after exposure to 1.7 pM insulin (sufficient to stimulate only the insulin receptor) showed that insulin stimulates protein synthesis in these cells as well as in the trophectoderm cells of the blastocyst. This finding suggests that in intact blastocysts, insulin may travel across the trophectoderm to the inner cell mass, acting anabolically on both tissues. Analysis of the agonistic effect of the B-10 antiserum showed there was no evidence of an unresponsive subpopulation of embryos. PMID- 1931042 TI - In vitro maturation of the potential for movement of carp spermatozoa. AB - Carp semen obtained from isolated fish after hormonal stimulation was highly variable in terms of volume of semen, osmotic pressure of the seminal plasma, and sperm capacity to move. Moreover, this last parameter was unstable when the spermatozoa were kept within the seminal plasma, and the present work was designed to investigate and possibly correct this phenomenon. Sperm potential movement was the major parameter studied and was measured by the percentage of motile cells in a final 3.000-fold dilution in a medium of low osmotic pressure in which sperm movement is known to occur (Morisawa and Suzuki, Science 210:1145 1147, 1980). This was completed with occasional measurements of flagellar beat frequencies and demembranation-reactivation of axonemal movement. The results showed that sperm potential movement was preserved upon dilution of the semen into cold 200 mM KCl medium and that semen of initially "poor" quality or spermatozoa that had lost their capacity to move during storage in the semen recovered gradually their potential movement during incubation at 2 degrees C in the same medium. The K+ dependence for both the conservation and the regeneration of sperm capacity to move showed a minimal requirement of 50 mM KCl in media of high osmotic pressure. Na+ ions had similar properties but not divalent cations. The K+ activation was not pH dependent between pH 9.03 and 6.04. Whatever the functional state of live spermatozoa, demembranation-reactivation occurred in ATP Mg2+. It is concluded that, with dilution of the semen in appropriate conditions, carp spermatozoa retain or acquire potential movement and therefore are a lower vertebrate spermatozoa model available year-round. In addition, obtaining potentially nonmotile sperm and reversion in vitro might be useful to study the control of in vitro maturation. PMID- 1931043 TI - Protein synthesis and phosphorylation patterns of bovine oocytes maturing in vivo. AB - To investigate protein synthesis and phosphorylation during bovine oocyte maturation in vivo, oocytes were collected at consecutive times after the preovulatory luteinizing hormone (LH) peak. Therefore, heifers treated for superovulation were ovariectomized between 3 and 20 h after the maximum of the LH peak. Subsequently, cumulus-enclosed oocytes, selected from nonatretic follicles greater than 10 mm, were radiolabeled with 35S-methionine or 32P-orthophosphate for 3 h and individually prepared for gel electrophoresis. Changes in the protein synthesis patterns were observed coinciding with germinal vesicle breakdown (GVBD). No changes were detected during the ensuing maturation period or coinciding with the extrusion of the first polar body. In addition, the protein phosphorylation patterns exhibited striking differences around GVBD. In particular, a phosphoprotein band of 19 kDa and the two heavily phosphorylated proteins with apparent molecular weights between 50 and 60 kDa were present in patterns of oocytes in the germinal vesicle stage. The results are discussed in relation to previous data obtained during maturation in vitro. PMID- 1931044 TI - Sperm analysis by flow cytometry using the fluorescent thiol labeling agent monobromobimane. AB - The fluorescent labeling agent monobromobimane (mBBr) was used to label thiols and disulfides (after reduction of sperm disulfides by dithiothreitol) in intact spermatozoa. Bimane-labeled sperm of several mammalian species were analyzed by flow cytometry (FCM) and examined by fluorescent microscopy. FCM analysis showed sperm thiol oxidation to disulfides during epididymal maturation. FCM of labeled mature spermatozoa showed differences among species in the sperm thiol content. Heterogeneity in thiol content of sperm within individual samples was also observed. In addition, FCM patterns showed heterogeneity among and within samples in the content of disulfides and their resistance to reduction. FCM analysis reflected the microscopic appearance of the labeled spermatozoa. FCM analysis of bimane-labeled spermatozoa offers a convenient method for the study of sperm thiol-disulfide status and permits detection of sperm subpopulations within an individual sample. FCM analysis of mBBr-labeled spermatozoa may serve as a test to evaluate sperm quality. PMID- 1931045 TI - Thiol status in human sperm. AB - The passage of spermatozoa along the epididymis is characterized by a gradual stabilization of intracellular organelles mainly through the oxidation of thiol groups. In this study, we examined the relationship between the thiol-disulfide status of human spermatozoa (using a specific fluorescent probe, monobromobimane) and routine semen analysis parameters. Fluorescence intensity was measured by spectrofluorimeter and its frequency distribution within samples, using a fluorescence-activated cell sorter. The mean proportion of reactive thiols SH/(SS + SH) in 29 semen samples was 29.8% +/- 2.5%. When comparing thiol labeling patterns, oligozoospermic samples differed from normozoospermic ones (P less than 0.05). However, within the normozoospermic group, no correlation was found between thiol-labeling patterns and routine sperm parameters or fertilizing capacity in vitro. No difference in thiol labeling patterns was found between "swim-up" and "whole semen" preparations. PMID- 1931046 TI - A monoclonal antibody, MN13, that recognizes specifically a novel substance between the postacrosomal sheath and the overlying plasma membrane in the mammalian sperm head. AB - Monoclonal antibody MN13 raised against mouse spermatozoa specifically recognizes the postacrosomal region of the sperm head in several mammalian species. Colloidal gold-immunoelectron microscopy of demembranated mouse spermatozoa indicated that the antigen is associated with the outer layer of the periodic substructure apparently linking the postacrosomal sheath to the overlying plasma membrane. The antigen recognized by MN13 may contribute to the intimate association of the postacrosomal sheath with the overlying plasma membrane. PMID- 1931047 TI - Maturation of guinea pig sperm in the epididymis involves the modification of proacrosin oligosaccharide side chains. AB - Proacrosin from guinea pig cauda epididymal sperm has a lower molecular weight compared with the testicular zymogen. In this study, we have examined the structural basis of this change and where the conversion in proacrosin molecular weight occurs during sperm maturation. Immunoblotting of trifluoromethanesulfonic acid-deglycosylated testicular and cauda epididymal sperm extracts with antibody to guinea pig testicular proacrosin demonstrated that the polypeptide backbones of proacrosins from the testis and cauda epididymal sperm had the same molecular weights (approximately 44,000). Keratanase, an endo-beta-galactosidase specific for lactosaminoglycans, partially digested testicular proacrosin but had no effect on proacrosin from cauda epididymal sperm. In extracts of testis, caput epididymis, and corpus epididymis analyzed by immunoblotting, anti-proacrosin recognized a major antigen with an apparent molecular weight (Mr) of 55,000, although a 50,000-Mr minor antigen began to appear in the corpus epididymis. By contrast, extracts of cauda epididymis, vas deferens, and cauda epididymal sperm had the 50,000 Mr protein as the only immunoreactive antigen. By enzymography following electrophoresis, the major bands of proteolytic activity in extracts of testis, caput epididymis, and corpus epididymis had 55,000 Mr. A band of protease activity with 55,000 Mr also appeared in extracts of the corpus epididymis. However, the most prominent bands of proteolytic activity in cauda epididymis, vas deferens, and cauda epididymal sperm had 50,000 Mr. In addition, two other major protease activities were detected with 32,000 and 34,000 Mr; the relationships of these proteases to proacrosin are unclear. From these results, we conclude that the oligosaccharides of proacrosin are altered during epididymal transit and that this modification occurs in the corpus epididymis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931048 TI - Characterisation of 24-kD proteins from rat testes using polyclonal sera reactive to human sperm antigens. AB - A group of antigens of 24-kD Mr from rat testes were characterised biochemically. These antigens were part of a larger molecule of approximately 200 kD. On treatment with disulfide bond reducing agent, the 200-kD molecule was reduced to subunits. Immunoreactivity was confined to a doublet of approximately 24 kD and a single band of approximately 50 kD Mr after the reduction. Glycoprotein in nature, this antigen shared immunoreactive epitopes with a 40-kD antigen on human spermatozoa. Antiserum raised in rabbits against the 24-kD antigen from rat testes reacted with antigens on the acrosome of human spermatozoa. Agglutination of sperm could be induced by the antiserum. The carbohydrate residue could be removed by mannosidase digestion. Chemical deglycosylation studies showed a slight decrease in molecular weight. Immunoreactivity was however not completely lost after chemical deglycosylation. Isoelectric focusing of the antigen identified nine isoelectric species. Two relatively minor species showed immunoreactivity. Acrosome-reacted spermatozoa showed loss of antigens from acrosome. PMID- 1931049 TI - Molecular cloning and expression of a novel adhesion molecule, SC1. AB - SC1, an integral membrane glycoprotein of 100 kd, is uniquely and transiently expressed on spinal cord motoneurons early in development and appears in peripheral neurons and several other tissues during development. SC1 has been purified by immunoaffinity techniques, and SC1 cDNA clones have been obtained by screening an E4 chick embryo phage expression library with a rabbit polyclonal antibody produced against purified SC1. The deduced protein sequence of 588 amino acids consists of a signal peptide, five immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail. The sequence is most similar to MUC18, reported as a tumor progression marker in human melanoma. Transfection of SC1 cDNA into mammalian cells leads to cell surface expression of SC1 antigen and a subsequent increase in cell-cell adhesion. SC1 molecules bind to each other via a homophilic adhesion mechanism, independently of calcium or magnesium ions. SC1 may have a role in lateral motor column formation or neurite growth or fasciculation. PMID- 1931050 TI - Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region. AB - Shaker potassium channels inactivate and recover from inactivation with multiple exponential components, suggesting the presence of multiple inactivation processes. We describe two different types of inactivation in Shaker potassium channels. N-type inactivation can occur as rapidly as a few milliseconds and has been shown to involve an intracellular region at the amino-terminal acting as a blocker of the pore. C-type inactivation is independent of voltage over a range of -25 to +50 mV. It does not require intact N-type inactivation, but is partially coupled to it. The kinetics of C-type inactivation are quite different for channels with different alternatively spliced carboxy-terminal regions. We have localized the differences in C-type inactivation between the ShB and ShA variants to a single amino acid in the sixth membrane-spanning region. N- and C type inactivation occur by distinct molecular mechanisms. PMID- 1931051 TI - Ectopic expression of sex peptide alters reproductive behavior of female D. melanogaster. AB - Sex peptide, a secreted component of the male accessory glands, has been shown to induce behavioral and physiological changes in mated Drosophila. We transformed flies with a hybrid gene containing an hsp70 promoter fused to a cDNA encoding sex peptide. Heat-induced ectopic expression of the peptide in transgenic virgin females altered their reproductive behavior, in the presence of courting males, to that observed in mated females. This demonstrates that the peptide is functional as expected. Time course studies revealed that the behavioral change appeared earlier than the stimulated ovulation. We have also introduced a modified sex peptide gene that is driven by the yp1 enhancer, conferring expression in adult females, and shown that these flies refuse mating constitutively in the presence of courting males and lay unfertilized eggs at the rate of mated females. PMID- 1931052 TI - Induction of adult-type nicotinic acetylcholine receptor gene expression in noninnervated regenerating muscle. AB - Expression of adult-type nicotinic acetylcholine receptors at the neuromuscular junction is thought to result from selective induction of their genes in endplate associated nuclei due to local neurotrophic control. However, denervation studies indicate that endplate-specific expression can be maintained in the absence of the nerve. We investigated the role played by the basal lamina in this expression by assaying for the adult-type-specific epsilon RNA in noninnervated regenerating muscle. We found that this RNA is locally expressed beneath the old endplates after 10 days of regeneration. At earlier times epsilon RNA is also found in areas other than the endplate region. These results indicate that in adult muscle the basal lamina contains all the components necessary to direct nicotinic acetylcholine receptor gene expression to the endplate. PMID- 1931053 TI - Acetylcholine receptor assembly is stimulated by phosphorylation of its gamma subunit. AB - Different combinations of Torpedo acetylcholine receptor (AChR) subunits stably expressed in mouse fibroblasts were used to establish a role for phosphorylation in AChR biogenesis. When cell lines expressing fully functional AChR complexes (alpha 2 beta gamma delta) were labeled with 32P, only gamma and delta subunits were phosphorylated. Forskolin, which causes a 2- to 3-fold increase in AChR expression by stimulating subunit assembly, increased unassembled gamma phosphorylation, but had little effect on unassembled delta. The forskolin effect on subunit phosphorylation was rapid, significantly preceding its effect on expression. The pivotal role of the gamma subunit was established by treating alpha beta gamma and alpha beta delta cell lines with forskolin and observing increased expression of only alpha beta gamma complexes. This effect was also observed in alpha gamma, but not alpha delta cells. We conclude that the cAMP induced increase in expression of cell surface AChRs is due to phosphorylation of unassembled gamma subunits, which leads to increased efficiency of assembly of all four subunits. PMID- 1931054 TI - The generation of neurons and oligodendrocytes from a common precursor cell. AB - We have used a recombinant retrovirus carrying the lacZ gene to study the developmental potential of precursor cells from the embryonic rat cerebral cortex in dissociated cell culture. Virus was used to label a small number of cultured cells genetically so that their fate could be determined. Infected clones were detected with an anti-beta-galactosidase serum, and the labeled cells were identified using monoclonal antibodies. The results revealed that most precursor cells generated a single cell type, the majority being either neurons or oligodendrocytes. However, a proportion of the neuronal clones also included oligodendrocytes. This proportion increased until embryonic day 16 when 18% of the neuronal clones were of this type. This suggests that during neurogenesis in the cerebral cortex there exists a cell with the potential to generate these two quite different neural cell types. PMID- 1931055 TI - Current practices and perspectives of health care in the Soviet Union. PMID- 1931056 TI - Documenting improved anesthesia outcome. PMID- 1931057 TI - Decreasing frequency of anesthetic cardiac arrests. AB - STUDY OBJECTIVE: To determine whether the anesthetic cardiac arrest rate decreased following the introduction of enhanced respiratory monitoring and increased safety awareness during the past decade. DESIGN: Epidemiologic study of surgical anesthetic morbidity as represented by intraoperative cardiac arrests. SETTING: Operating room suite of a large university hospital. PATIENTS: 241,934 patients undergoing surgery over a period of 20 years. INTERVENTIONS: Anesthetic cardiac arrest rates from two decades were compared. The first decade (1969 to 1978) predated safety initiatives, while the second (1979 to 1988) included them. MEASUREMENTS AND MAIN RESULTS: Anesthetic cardiac arrests were identified, and their causes (respiratory vs nonrespiratory) and preventability (identifiable error) were determined shortly after their occurrence, as part of an ongoing study initiated in 1969. They provided numerators for rate calculations; total surgical anesthetics provided the denominators. The anesthetic cardiac arrest rate decreased by one-half from the first decade (2.1 arrests/10,000 anesthetics) to the second (1.0/10,000), a significant difference (p = 0.032, Fisher's Exact Test). The rate for preventable arrests due to respiratory causes declined significantly from 0.8/10,000 to 0.1/10,000 (p = 0.013) and accounted for most of the observed decrease in the overall anesthetic cardiac arrest rate. The rates for preventable nonrespiratory arrests and nonpreventable arrests did not change significantly. CONCLUSIONS: The results support the hypothesis that improved respiratory monitoring was effective in decreasing anesthetic morbidity. PMID- 1931058 TI - Hazards of a new, clear, unmarked polyvinylchloride tracheal tube designed for use with the Nd-YAG laser. AB - STUDY OBJECTIVE: To compare a new, clear, unmarked polyvinylchloride (PVC) tracheal tube marketed for use during Neodymium-Yttrium-Aluminum-Garnet (Nd-YAG) laser surgery with a conventional marked PVC tracheal tube. SETTING: Research laboratory of a metropolitan, university-affiliated medical center. DESIGN AND INTERVENTIONS: An Nd-YAG laser set to 70 watts was directed at the tracheal tubes through which 5 L/min of oxygen (O2) flowed. The laser was actuated for 1 minute or until combustion occurred. MEASUREMENTS AND MAIN RESULTS: The conventional marked tracheal tube was unaffected when the laser was directed at an unmarked portion of the tube. Laser impingement onto the marked portions of the tube led to combustion after 2.6 seconds. The clear, unmarked PVC tracheal tube was unaffected by 1 minute of Nd-YAG laser fire. When blood or mucus was applied to this tracheal tube, however, Nd-YAG laser actuation resulted in a fire in less than 6 seconds. CONCLUSIONS: The clear, unmarked Sheridan PVC tracheal tube is not recommended for laser airway surgery. PMID- 1931059 TI - Knee-chest position improves pulmonary oxygenation in elderly patients undergoing lower spinal surgery with spinal anesthesia. AB - STUDY OBJECTIVE: To define the effect of the knee-chest position on pulmonary oxygenation in patients who underwent lower spinal operations under spinal anesthesia. DESIGN: Clinical, prospective study. SETTING: Inpatient anesthesia and orthopedic surgery clinic at a municipal hospital. PATIENTS: Fifty-six patients (30 males and 26 females) who underwent lower spinal surgery under spinal anesthesia. INTERVENTIONS: After administering hyperbaric tetracaine solution and fixing the anesthesia level in the supine position for 15 minutes, patients were turned to the knee-chest position. They breathed room air normally. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas tensions were measured in the supine position 15 minutes after administration of the tetracaine solution and 15 minutes after turning patients to the knee-chest position. Patients were classified into six groups according to their age: patients in their teens and 20s, 30s, 40s, 50s, 60s, and 70s. In the supine position, the mean values of the alveolar arterial oxygen tension difference (A-aDO2) of patients in their 50s, 60s, and 70s were significantly higher than those of patients in their teens and 20s, 30s, and 40s. In the knee-chest position, these high values of A-aDO2 in the older patient groups decreased significantly, thereby eliminating any significant difference in A-aDO2 among all age groups. To determine the mechanism of the improvement of pulmonary oxygenation in the elderly patients, the effect of the knee-chest position on lung volumes was studied in eight young volunteers. CONCLUSION: A significant improvement of pulmonary oxygenation was seen in elderly patients who underwent lower spinal operation with spinal anesthesia when they were turned to the knee-chest position. The knee-chest position has a beneficial effect on pulmonary oxygenation in elderly patients who are given spinal anesthesia. PMID- 1931060 TI - Midazolam potentiates thiopental sodium anesthetic induction in patients. AB - STUDY OBJECTIVE: To test the hypothesis that midazolam potentiates thiopental sodium-induced unconsciousness. DESIGN: Randomized, double-blind study. SETTING: A university medical center. PATIENTS: Fifty nonpremedicated ASA physical status I and II adult patients scheduled for eye surgery. INTERVENTIONS: Intravenous (IV) injections of thiopental sodium in doses ranging from 1.0 mg/kg to 4 mg/kg with or without the addition of midazolam 0.02 mg/kg. MEASUREMENTS AND MAIN RESULTS: Inability to open eyes on command was used as an end point of anesthesia and the dose-response curves were determined using a probit procedure. A dose of 0.02 mg/kg, which constitutes less than one-tenth of the hypnotic ED50 value for midazolam, potentiated thiopental sodium anesthesia. The thiopental sodium ED50 value was decreased from 2.4 mg/kg to 1.6 mg/kg (p less than 0.001). Midazolam also reduced individual variability in the response to thiopental sodium. As a result, the thiopental sodium dose that reliably induced any nonpremedicated patient decreased from 6 mg/kg (ED99 of 5.57 mg/kg) to 2.5 mg/kg (ED99 of 2.37 mg/kg). CONCLUSIONS: A subhypnotic dose of midazolam potentiates thiopental sodium-induced unconsciousness. This effect suggests the possibility that midazolam enhances barbiturate binding. PMID- 1931061 TI - A comparison of thromboelastogram and template bleeding time in the evaluation of platelet function after aspirin ingestion. AB - STUDY OBJECTIVE: To compare template bleeding time (TBT) with thromboelastography (TEG) in human subjects after aspirin ingestion. DESIGN: Healthy volunteers were given a single 650 mg dose of aspirin or a dose of 650 mg of aspirin on three successive days. TBT and TEG studies were performed prior to aspirin ingestion and 4, 24, 72, and 168 hours after ingestion. SETTING: Inpatient operating room support area at the UCLA Center for Health Sciences. VOLUNTEERS: Residents and nurses who were in good general health, had not taken aspirin for 2 weeks, had normal platelet counts, and had no evidence of bleeding or coagulation disorders. INTERVENTION: TBT and TEG studies were performed prior to and after the ingestion of aspirin. MEASUREMENTS AND MAIN RESULTS: TBT studies were significantly prolonged at 4, 24, and 72 hours compared with controls. Maximum bleeding time prolongation occurred 24 hours after aspirin ingestion. Bleeding time returned to control values by the end of 168 hours (1 week). No TEG parameter was significantly changed by aspirin ingestion. CONCLUSION: TEG results may not identify patients who have an increased bleeding time as a result of aspirin ingestion. PMID- 1931062 TI - Magnetic resonance imaging implications of metal-reinforced spinal microcatheters. AB - STUDY OBJECTIVE: To estimate the magnitude behavior of ferrous-alloy, wire reinforced microcatheters for subarachnoid anesthesia and the possible hazards of exposing patients to magnetic resonance imaging (MRI) after accidental catheter fracture within the subarachnoid space. DESIGN: Open, qualitative in vitro study. SETTING: MRI facility of a university-affiliated medical center. MEASUREMENTS AND MAIN RESULTS: Measurements were made of the angular deflection of 28-gauge and 32 gauge TFX catheters from their resting alignment by a small bar magnet. Mobility of 28-gauge catheter fragments 3.0 to 3.5 cm in length and 3.3 to 4.0 mg in mass were tested (1) when lying free on a polished surface in an MRI magnetic field of 1.5 tesla and 60 cm from the magnetic casing, and (2) when mounted on a mildly viscous agar surface 40 to 50 cm from the magnetic casing. Catheters were attracted to a small bar magnet and could be pulled out of alignment by the magnetic attraction to a degree inversely proportional to their caliber. Catheter fragments released in a magnetic field of 1.5 tesla flew from a glass surface and attached themselves firmly to the magnet casing, while catheter fragments adhering to an agar surface were not levitated but were rotated from their resting orientation. CONCLUSIONS: The microcatheters under test exhibited marked magnetic properties. Two questions arise: First, should MRI be avoided in patients where broken TFX catheter fragments may lie partly or completely within the subarachnoid space? Second, should ferrous metallic strengthening wire be replaced by a nonmetallic fiber of comparable or greater tensile strength? Further in vitro studies are indicated to answer these questions. PMID- 1931063 TI - Single-dose caudal epidural morphine in children: safe, effective, and easy. AB - STUDY OBJECTIVE: To determine whether a single epidural dose of morphine sulfate is effective in providing 12- to 24-hour pain relief in children. DESIGN: A chart review of 113 consecutive pediatric patients having received a single dose of epidural morphine. SETTING: An inpatient anesthesia and surgical service at a regional children's hospital. PATIENTS: One hundred thirteen consecutive pediatric patients from 2 months to 15 years old who underwent major orthopedic, thoracic, genitourinary, or abdominal surgical procedures. INTERVENTIONS: 60 micrograms/kg of preservative-free morphine sulfate was administered epidurally after induction of anesthesia but before surgery began. The epidural space was accessed caudally, and a total volume of 1 ml/kg to a maximum of 20 ml was injected. No other intraoperative opioids were administered. MEASUREMENTS AND MAIN RESULTS: Forty-seven percent of the patients required no parenteral analgesic for 12 hours after receiving a single dose of epidural morphine, and only 10% required more than 0.1 mg/kg of parenteral morphine during this 12-hour period. For infants younger than 1 year of age, the supplemental intravenous (IV) morphine requirement was almost identical to that of the entire study population. There was no respiratory depression. All patients except those who had thoracotomies were followed on regular pediatric nursing floors. CONCLUSIONS: Single-dose caudal epidural morphine in children is safe and effective when administered intraoperatively prior to surgery as the only opioid and coupled with appropriate monitoring, nursing education, and follow-up by the anesthesiologist. These patients can be followed on regular nursing floors with proper monitoring. PMID- 1931064 TI - The differential cost of anesthesia and recovery with propofol-nitrous oxide anesthesia versus thiopental sodium-isoflurane-nitrous oxide anesthesia. AB - STUDY OBJECTIVE: To assess the recovery room profile of propofol in outpatient anesthesia and to compare it to the profile of a standard technique. DESIGN: A comparative, randomized, double-blind, third-party open study. SETTING: Ambulatory Surgery Center at The Emory Clinic. PATIENTS: Ninety-nine ASA physical status I, II, or III nonpregnant female patients who had been diagnosed as needing breast biopsies. INTERVENTIONS: All patients were given 1 microgram/kg of fentanyl prior to induction. Those in the propofol group were induced with 2.0 to 2.5 mg/kg of propofol and maintained with a 100 to 200 microgram/kg/min infusion of propofol with nitrous oxide (N2O) in oxygen (O2). In the thiopental sodium isoflurane group, patients were induced with 4.0 to 5.0 mg/kg of thiopental sodium and maintained with isoflurane and N2O in O2. MEASUREMENTS AND MAIN RESULTS: Recovery from anesthesia was assessed by an evaluator who was unaware of the anesthetic technique used for each patient. Immediate recovery time was measured in terms of awakening, response to verbal command, and orientation to time and place. A brief postoperative follow-up questionnaire was completed to assess the patients' subjective feelings regarding their ability to eat, concentrate, and resume normal activities. In the thiopental sodium-isoflurane group, 15 of 50 patients (30%) had nausea and vomiting, but in the propofol group, only 4 of 49 patients (8.1%) had nausea and vomiting (p less than 0.01). The latter group resumed normal activity (i.e., reading and watching television) 7.93 +/- 0.76 hours postanesthesia, whereas the thiopental sodium-isoflurane group resumed normal activity 17.02 +/- 1.21 hours postanesthesia (p less than 0.001). Patients in the propofol group returned to work in an average of 1.5 +/- 0.09 days, compared with 2.0 +/- 0.09 days for the thiopental sodium-isoflurane group (p less than 0.001). CONCLUSIONS: The propofol group needed less nursing care and returned to more productive activity earlier than did the thiopental sodium-isoflurane group. PMID- 1931065 TI - The effects of thiopental sodium on fentanyl-induced muscle rigidity in a human model. AB - STUDY OBJECTIVE: To describe a safe human model in which to study the treatment of fentanyl-induced muscle rigidity and report on the efficacy of thiopental sodium for this purpose. DESIGN: Randomized, observer-blinded comparison of regimens. SETTING: Inpatient surgery at a university-affiliated teaching hospital. PATIENTS: Thirty patients scheduled for elective surgery in whom the administration of high-dose fentanyl was felt to be appropriate and who experienced severe muscle rigidity in the chest, abdomen, and upper extremities after the fentanyl was administered. INTERVENTIONS: One arm was isolated from circulation with a blood pressure (BP) cuff inflated to 100 mmHg above systolic blood pressure (SBP), after which fentanyl 25 to 50 micrograms/kg was administered intravenously (IV) at a rate of 1 mg/min in the contralateral arm. If severe muscle rigidity became apparent in three muscle groups (the chest, abdomen, and arms), patients were either (1) observed for 3.5 minutes without further intervention, (2) given thiopental sodium 1.5 mg/kg IV, followed 120 seconds later by succinylcholine 1 mg/kg IV, or (3) given succinylcholine 1 mg/kg IV, followed 120 seconds later by thiopental sodium 1.5 mg/kg IV. MEASUREMENTS AND MAIN RESULTS: A single observer, blinded to the technique, evaluated and recorded the degree of muscle rigidity present in the chest wall, abdomen, and upper extremities (one isolated from the circulation by a tourniquet) 90 seconds and 3.5 minutes after the onset of muscle rigidity in the control group and 90 seconds after the administration of either thiopental sodium or succinylcholine in the two experimental groups. The observer was the same individual in all instances. The muscle rigidity associated with the administration of high-dose fentanyl was clinically attenuated by the administration of thiopental sodium, especially in the extremities. Succinylcholine was more effective than thiopental sodium in producing muscle flaccidity in all muscle groups not isolated by a tourniquet. In no case did the muscle rigidity compromise our ability to oxygenate the patient adequately. CONCLUSIONS: Thiopental sodium does blunt the degree of muscle rigidity induced by high-dose fentanyl, though not as effectively as does succinylcholine. One can safely isolate an extremity prior to the administration of high-dose fentanyl and a muscle relaxant, intubate the trachea, and ventilate a patient, while retaining the ability to study the effect of centrally acting drugs on fentanyl-induced rigidity in the isolated extremity. PMID- 1931066 TI - Epidural anesthesia for a cesarean section in a patient with pulmonary atresia and ventricular septal defect. AB - The perioperative management and the pathophysiology of a parturient with pulmonary atresia, ventricular septal defect, patent ductus arteriosus Botalli (PDA), and pulmonary hypertension are described. The patient previously had a cesarean section under general anesthesia and was currently managed with an epidural block. The outcome was successful for the mother. The postoperative period of the premature infant was characterized by hyaline membrane disease, with its typical sequelae. PMID- 1931067 TI - Airway obstruction following application of cricoid pressure. AB - The widely practiced rapid-sequence induction with application of cricoid pressure is designed to facilitate endotracheal intubation in patients considered to be at high risk of aspiration. We describe a case in which this maneuver was performed on a patient with an undiagnosed traumatic injury to the larynx. The resulting airway obstruction required emergency surgical intervention. The clinical presentation, diagnosis, and management of such injuries are discussed. PMID- 1931068 TI - Total airway obstruction with neck extension: airway management of a patient with pharyngeal tumor. AB - Airway obstruction with the induction of anesthesia in children is common. Normally, neck extension with jaw thrust improves the airway. Flexion typically completes the obstruction. With the presence of a pharyngeal tumor, these relationships may not be the same. We present a case of complete airway obstruction with neck extension in the presence of a nasopharyngeal tumor. Flexion rather than extension of the neck relieved this airway obstruction. We highly recommend radiologic studies with neck extension and flexion in such cases. PMID- 1931069 TI - Application of the Mizus endotracheal obturator in tracheostomy and tentative extubation. AB - A variety of catheters, stylets, and obturators have been used to assist with problems in airway management. Obturators specifically designed for airway use are now available in different sizes. The pediatric-size obturators (2.2 mm diameter) can be placed into the airways of most patients without apparent respiratory impairment. Use of these obturators to preserve a path to the airway is described in cases of tracheostomy and tentative extubation. The advantages and disadvantages inherent in the use of such obturators are described. PMID- 1931070 TI - Airway involvement and anesthetic management in Goltz's syndrome. AB - A 13-year-old girl with Goltz's (Goltz-Gorlin) syndrome (focal dermal hypoplasia) and cloacal exstrophy underwent day surgery cystoscopy. During the administration of inhalation anesthesia by mask, persistent partial upper airway obstruction was noted. Direct laryngoscopy unexpectedly showed variously sized verrucous lesions in the hypopharynx and supraglottic larynx, and the vocal cords and trachea could not be visualized. The patient later returned for a complete endoscopic examination, followed by cup forcep and laser excision of these verrucous and pedunculated lesions, and remained intubated in the intensive care unit (ICU) for 48 hours following this procedure. Airway management and pathology specific to this rare disorder are discussed. PMID- 1931071 TI - Anesthetic management for acute intermittent porphyria: choice of muscle relaxant. PMID- 1931072 TI - Myositis ossificans progressiva. PMID- 1931073 TI - Cytokine receptors of the lung. AB - There has been a dramatic increase in studies on the potential role of cytokines in controlling the processes of inflammation, injury, and repair in the lung. A vast array or network has emerged including all of the cells that produce the various cytokines that have been identified and the target cells that respond to these mediators. The network continues to expand as new cytokines and cytokine receptors are identified. It is generally accepted that responses to cytokines are mediated through cell surface transmembrane receptors, so that key to unraveling this complex system is an understanding of what mechanisms control signal transduction via these receptors and how cytokine interaction with specific receptors results in cell- and cytokine-specific target cell responses. This review presents a detailed examination of individual receptor structures and how these data can lead to information about signaling mechanisms; the exciting new findings of naturally occurring receptor inhibitors; and how regulation of receptor levels might control target cell responses. PMID- 1931074 TI - Experimental hypersensitivity pneumonitis in the rat: histopathology and T-cell subset compartmentalization. AB - The pathogenesis of hypersensitivity pneumonitis (HP) appears to depend largely on T-cell specificity and interactions with monocytes/macrophages. We studied T cell subset populations, defined by surface membrane markers with putative functional correlates, present in lung parenchyma and bronchoalveolar spaces of sensitized LEW rats following acute and chronic inhalational challenges with antigen. Our initial hypothesis was that the CD4+ RT6- (TDH) subset, the effector cell of delayed hypersensitivity, would dominate in HP lesions and that CD8+ RT6+ (TS) or CD8+ CD45R+ (TS) subsets, constituting putative suppressor T-cell populations, would dominate in lungs of animals with resolving lesions. We found, however, a heterogeneous population involving all eight of the T-cell subsets that were evaluated. Percentages of the RT6+ phenotype diminished as T cells moved from peripheral blood to lung. Dominant numbers of T cells in acute HP included CD8+ RT6- (TCYT) and CD8+ CD45R- (TCYT) subsets, with putative cytotoxic T-cell activity, in addition to CD4+ RT6- (TDH) cells. We did not demonstrate increases in T suppressor cells as the disease waned. PMID- 1931075 TI - Most human pulmonary infiltrating lymphocytes display the surface immune phenotype and functional responses of sensitized T cells. AB - Pulmonary infiltrating lymphocytes (PIL) isolated directly from human lung were examined for their surface immune phenotype by monoclonal antibody staining and cytofluorimetry. In order to purify PIL, resected lungs were enzymatically digested with collagenase and DNase and subjected to density centrifugation and nylon-wool column separation. In some cases, CD4+ lymphocytes were further purified with alpha CD8 and complement. The majority of pulmonary lymphocytes were CD2+ (87 +/- 1%) and CD3+ (73 +/- 4%). Virtually all of the CD3+ PIL were Ti alpha beta+. Greater than 90% of both CD4+ or CD8+ PIL were CD45RO+ and CD45RA-, consistent with prior antigen sensitization in vivo. A subset of CD4+ PIL (34 +/- 4%) expressed Leu8, the human congener of the murine MEL-14 lymphocyte homing receptor, whereas most homologous CD4+ peripheral blood lymphocytes were Leu8+ (75 +/- 8; P less than 0.01). HLA-DR surface antigens were expressed by 45 +/- 5% of CD4+ PIL versus 9 +/- 1% of CD4+ peripheral blood lymphocytes (P less than 0.001). There was no significant difference in the percentage of low-affinity interleukin-2 (IL-2) receptor-positive CD4+ lymphocytes in lung and blood (9 +/- 3% versus 13 +/- 2%). Analysis of the DNA synthetic cell cycle showed that approximately 5% of blood CD4+ lymphocytes and approximately 25% of CD4+ PIL were in S/G2/M. Compared to homologous blood T cells, purified PIL displayed enhanced proliferative responses to IL-2 and diminished responses to the lectin phytohemagglutinin. Lectin-stimulated PIL showed greater secretion of interferon gamma and IL-2 than did blood lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931076 TI - Tumor necrosis factor plays an essential role in determining hypersensitivity pneumonitis in a mouse model. AB - We examined the importance of the cytokine tumor necrosis factor-alpha (TNF alpha) in a mouse model of hypersensitivity pneumonitis (HP). Mice of the C57BL/6 strain were instilled intranasally 3 days/wk for 3 wk with 150 micrograms of the actinomycete Faenia rectivirgula (Micropolyspora faeni) to induce HP as a model of farmer's lung. This experimental model was associated with a progressive inflammation in the lungs of challenged mice, seen histologically as cellular infiltrates of large quantities of macrophages and lymphocytes and some neutrophils. The disease in challenged mice treated with a control rabbit serum was also associated with a substantial release of tumor TNF-alpha (up to 80 U/ml of TNF-alpha in the bronchoalveolar lavage [BAL] at 3 wk after beginning of treatment) and interleukin-1, which peaked at 1 wk (approximately 300 U/ml) and diminished thereafter. A very large increase in BAL cell number (11-fold increase versus saline controls) and an enhanced release potential for TNF-alpha by alveolar macrophages was also seen. Lung fibrosis was also evident in challenged animals, as demonstrated by a 2-fold increase in hydroxyproline levels. Infusion of challenged mice with a rabbit polyclonal antibody against TNF-alpha (2 mg/wk) completely abrogated the disease, as mice so treated had normal lung histology. Anti-TNF-alpha blocked cellular recruitment in the lungs (only a 2-fold increase at week 3); it also completely abolished TNF-alpha secretion in the BAL and drastically reduced interleukin-1 levels in this fluid. Anti-TNF-alpha also abolished lung index increases and lung fibrosis, with both parameters similar to that of saline-instilled mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931077 TI - The response of a human bronchial epithelial cell line to histamine: intracellular calcium changes and extracellular release of inflammatory mediators. AB - Epithelial cells are likely to modulate inflammation and tissue repair in the airways, but the factors responsible for these processes remain unclear. Because human airway epithelia are infrequently available for in vitro studies, transformed epithelial cell lines are of interest as models. We therefore investigated the response of an SV-40/adenovirus-transformed human bronchial epithelial cell line (BEAS-2B) to histamine, a mediator with relevance for airway diseases. The intracellular calcium response to histamine (10(-4) M) was measured, using Fura-2 and microspectrofluorimetry. Histamine induced a transient increase in intracellular calcium that originated from intracellular sources; this effect was inhibited by the H1 receptor antagonist diphenhydramine, suggesting that BEAS cells retain functioning histamine receptors. BEAS cells were grown to confluence on microporous, collagen-coated filters, allowing measurement of vectorial release of soluble mediators. Monolayers exposed to histamine for 30 min released interleukin-6 and fibronectin in the apical direction, in a dose-dependent manner. Little eicosanoid production was induced by histamine, either in the apical or the basolateral direction, although BEAS cells constitutively produced small amounts of prostaglandin E2 and 15-HETE. However, these cells formed large amounts of eicosanoids in response to ozone exposure as a positive control. Comparison of our data with published reports for human airway epithelia in primary culture suggests that the BEAS cell line is, in a number of respects, a relevant model for the study of airway epithelial responses to a variety of stimuli. PMID- 1931078 TI - Pulmonary fibroblast expression of interleukin-8: a model for alveolar macrophage derived cytokine networking. AB - The pulmonary fibroblast's (PF) unique location allows it to communicate in a bidirectional fashion between the vascular compartment and alveolar airspace, placing it in a strategic position for the elicitation of inflammatory leukocytes into the lung. In this study, we demonstrate that PF may contribute to pulmonary inflammation through the production of a potent neutrophil chemotactic factor, interleukin (IL)-8. PF-derived IL-8 expression was dependent upon stimulation by either tumor necrosis factor (TNF) or IL-1 but not lipopolysaccharide (LPS). Both TNF and IL-1 stimulation of PF resulted in a time- and dose-dependent expression of steady-state levels of mRNA, antigen, and specific chemotactic activity consistent with IL-8. Because it was apparent that cytokine networking may exist in the lung between alveolar macrophage (AM)-derived cytokines and the production of PF-derived IL-8, we next examined an in vitro model of cellular communication within the lung. We determined that LPS-stimulated AM-conditioned media induced significant levels of PF-derived IL-8 mRNA, which was inhibited by preincubation with specific neutralizing TNF and IL-1 beta antibodies. Furthermore, when AM were directly co-cultured with PF and stimulated with LPS, the kinetic analysis of PF-derived antigenic expression of IL-8 was shifted toward the right. This suggested that PF-derived IL-8 expression in co-culture was first dependent upon activation of the AM by LPS and subsequent elaboration of macrophage inflammatory mediators. These data provide evidence that cytokine networking between AM and PF may be operative in the lung, culminating in the generation of IL-8 and elicitation of inflammatory leukocytes. PMID- 1931079 TI - Common structural motifs in proteins of the extracellular matrix. AB - Proteins of the extracellular matrix are composed of many structurally and often functionally different autonomous domains which frequently occur as modular units in several different extracellular matrix proteins, but also in proteins of different origin. Some domains serve related assembly functions in different proteins but for domains involved in cell attachment and other cellular activities only a few generalizations are possible. PMID- 1931080 TI - Fibronectin: from gene to protein. AB - Recent advances in several key areas of fibronectin biology are discussed. These include its expression, from transcription to secretion of dimers, the structural requirements for several of the binding activities, potential roles for alternatively spliced segments in cell adhesion, and the assembly of a fibronectin matrix. PMID- 1931081 TI - Genetic analysis of proteoglycan structure, function and metabolism. AB - Significant progress has been made in understanding the structure, function, and metabolism of proteoglycans. Many of the advances derive from the application of recombinant DNA methodology to their core proteins and from the characterization of animal cell mutants altered in glycosaminoglycan synthesis. PMID- 1931082 TI - Extracellular matrix regulation of growth factor and protease activity. AB - Extracellular matrices bind many growth factors, proteases, and protease inhibitors. These interactions not only localize these molecules to the pericellular environment, but also modulate their biological activities. Recent evidence suggests that some growth factors may be active in vivo primarily in complexes with extracellular matrix molecules and that this interaction may be essential to their activity. PMID- 1931083 TI - Dominant and recessive genes involved in tumor cell invasion. AB - The past year has been the discovery and further analysis of several genes and protein products that are critically involved in the generation of invasive and metastatic tumor cells. Like oncogenes and tumor suppressor genes, the genes responsible for invasive and metastatic phenotypes can function in a dominant or recessive fashion. In this review, particular emphasis will be given to the dominantly acting genes encoding the cell adhesion molecule CD44 and the motility factor scatter factor, and the recessively acting genes encoding the cell adhesion molecule E-cadherin and nm23. PMID- 1931084 TI - Integrins as mechanochemical transducers. AB - A recent resurgence of interest in mechanical forces and cell shape as biological regulators has revealed extracellular matrix as the site at which forces are transmitted both to and from cells. at the same time, great advances have been made in terms of defining cell-surface integrin receptors as transmembrane molecules that mediate cell attachment and physically interlink extracellular matrix with the intracellular cytoskeleton. Convergence of these two lines of research has begun to elucidate the molecular mechanism by which cells sense physical forces and transduce mechanical signals into a biochemical response. PMID- 1931085 TI - Transmembrane molecular assemblies in cell-extracellular matrix interactions. AB - Several new interactions have been identified and proteins characterized in focal adhesions. Together they suggest alternative or parallel linkages between actin filaments and members of the integrin family of extracellular receptors. Transformed cells continue to serve as models for studying the assembly and disassembly of these adhesions. PMID- 1931086 TI - Transmembrane molecular assemblies regulated by the greater cadherin family. AB - The cadherin family of cell-cell adhesion molecules is turning out to be much more diverse than previously thought, with members involved in several kinds of intercellular junctions. The adhesive specificity and cytoskeletal interaction of these members varies. Their cytoplasmic terminals are specialized for binding several families of 'mediator' proteins which interconnect to the actin or intermediate filament systems. These multi-molecular complexes have roles not only in cell-cell adhesion, but also in intracellular signalling of developmental information. PMID- 1931087 TI - Coordinate interactions of protein tyrosine kinases and protein tyrosine phosphatases in T-cell receptor-mediated signalling. AB - T-cell receptor stimulation leads to a rapid increase in tyrosine phosphorylation which is regulated by both the CD45 transmembrane protein tyrosine phosphatase and by intracellular protein tyrosine kinases. The Src-family members, Fyn and Lck, have been implicated in T-cell receptor signalling and may be regulated by CD45. PMID- 1931088 TI - Protein tyrosine phosphorylation and the adhesive functions of platelets. AB - The intracellular signalling pathways that mediate changes in cell behavior induced by extracellular matrix and cell adhesion molecules are poorly understood. Studies on the regulation of tyrosine phosphorylation in platelets indicate that cell-to-cell aggregation mediated by fibrinogen binding to its integrin-family receptor, GP IIb-IIIa, and events regulated by the putative adhesion receptor, GP IV (CD36), involve tyrosine phosphorylation. Thus, tyrosine phosphorylation is implicated in cellular events crucial for hemostasis. It may also be involved in signaling mediated by integrin receptors in other cell types. PMID- 1931089 TI - Cell-to-cell contact and extracellular matrix. PMID- 1931090 TI - Effects of warm ischemia following harvesting of allograft cardiac valves. AB - The clinical use of cryopreserved allograft valves is rapidly increasing. Viability of valve leaflet fibroblasts has been proposed to be critical to durability. Harvesting of allograft valves involves variable warm ischemia times, defined as the time from cessation of donor heart beat to initial cooling for transport. This ischemic period has been implicated as one of the more critical periods of injury to leaflet cell, even though adequate characterization of this potentially injurious phase has never been accomplished. The present study was undertaken to characterize the metabolic response to warm ischemia in a porcine valve leaflet model. Valve handling was similar to clinical valve harvest and transport protocols. Injury was assessed by protein (1H) and phosphorus (31P) magnetic resonance spectroscopy of 224 porcine semilunar valves. Leaflets were analyzed over time for lactate accumulation and ATP degradation. A radiolabelled incubation assay (48 valves) was used to measure proline accumulation by fibroblasts. Electron microscopy was performed on 36 valves with varying warm ischemia times. ATP stores were entirely depleted after 2 h hypoxia (p less than 0.05). However, lactate continued to accumulate over 24 h. Although aerobic metabolism ceased after 2 h warm ischemia, anaerobic metabolism continued for up to 24 h, which may represent an extended window for harvesting fresh tissue for allograft valve implantation. PMID- 1931091 TI - Diagnostic and therapeutic strategy in malignant pleural mesothelioma. AB - We retrospectively analysed 301 patients with diffuse malignant pleural mesothelioma (235 male, 66 female; median age 59 years). Prognosis depended significantly on patient age, evidence of pain, loss of weight, tumour cell type, stage, local and distant metastasis, involvement of peritoneum and surgical treatment. The overall median survival rate was 238 days, after extended pleuropneumonectomy 284 days, and after decortication 315 days - significantly better than the prognosis in patients without surgical treatment or exploratory thoracotomy. Pleuropneumonectomy should only be considered in young patients with an epithelial cell-type tumour (possibly with adjuvant chemotherapy). Decortication seems nowadays to be the treatment of choice. PMID- 1931092 TI - Surgical treatment of airway obstruction associated with congenital heart disease in infants and small children. AB - In the last 12 years, 21 patients age 1 month to 5 years (median, 7 months) underwent surgical treatment for severe airway obstruction associated with congenital heart disease. Plico-suspension of the pulmonary artery was carried out in 14 patients with documented severe left bronchial compression by a distended pulmonary artery together with repair of ventricular septal defects (11 patients), repair of large coronary artery fistula (1), division of ductus (1) and pulmonary artery banding (1), with subsequent significant relief of compression. Aortopexy was used in 2 patients with documented severe tracheal compression by a right aortic arch. Five patients had congenital tracheal stenoses (3 extensive, 2 localized). Two of 3 patients with associated complex intracardiac anomalies underwent concomitant repair of both lesions with the use of cardiopulmonary bypass and 1 had a tracheoplasty and pulmonary artery banding. Tracheal reconstruction with a cartilaginous graft together with repair of pulmonary artery sling was carried out in 2 infants. Nineteen patients are alive and well, at a mean follow-up of 87 months. In conclusion, we advocate early aggressive surgical intervention to both lesions to obtain a better result in the management of infants and small children with this difficult and often fatal combination. PMID- 1931093 TI - Heparin-coated cardiopulmonary bypass circuits reduce blood cell trauma. Experiments in the pig. AB - Blood cell trauma and postoperative bleeding remain important problems in cardiopulmonary bypass (CPB). We compared heparin-coated with non-coated circuits in the pig. Twenty animals were perfused for 2 h at normothermia using membrane oxygenators (Bentley Bos 50). Two groups were studied. In the non-coated group (NC, n = 11) the CPB circuits used were without a heparin coating. This group had systemic heparinization of 400 IU/kg to maintain an ACT (activated clotting time) of over 400 s during CPB. In the coated group (C, n = 9), all surfaces exposed to blood in the CPB circuits were heparin-coated. This group had the heparin dose reduced to 25% (100 IU/kg) without further administration regardless of ACT. During CPB, group C displayed shorter ACT (per definition), higher platelet count, platelet adhesion and lower fibrinolysis and haemolysis (P less than 0.05) as compared to group NC. No thromboembolic events were detected during CPB. Three animals in group NC and 4 animals in group C were weaned from CPB and protaminized. Four hours postoperatively, the leucocyte consumption was two-fold greater and blood loss about four-fold greater in group NC as compared with group C (P less than 0.05). Perfusion with heparin-coated surfaces reduces blood cell trauma. The decreased postoperative blood loss observed in group C is probably explained by the reduced dosages of heparin and protamine. PMID- 1931094 TI - Transesophageal echocardiographic evaluation in mechanically assisted circulation. AB - Transesophageal echocardiography (TEE) has assumed an increasing importance in cardiothoracic surgery, but its use in patients with mechanically assisted circulation is unclear. We performed TEE in 11 patients: total artificial heart (TAH) 2, right ventricular assist device (RVAD) 2, left ventricular assist device (LVAD) 6, biventricular assist device (BVAD) 1. TEE was helpful in three areas. (1) selection of the assist device (AD): evaluation of left and right ventricular function allows differentiation of left, right or biventricular failure. (2) management of patient and optimization of pump performance: in all patients, correct cannula position and pump flow could be identified. Right ventricular failure in the presence of LVAD was found to cause hemodynamic instability in 4 patients. In 1 patient with repeated RV dilation and hypotension despite RVAD, TEE allowed optimal pump settings to be determined. (3) weaning from AD: Recovery of ventricular function can be assessed prior to weaning and repeatedly monitored during weaning. TEE in TAH is limited to problems such as identification of atrial thrombus or inflow valve dysfunction. We conclude that TEE is useful in the setting of mechanically assisted circulation for AD selection, improvement of patient management, optimization of pump performance and during weaning from AD. PMID- 1931095 TI - New nomenclature and computerized programme of graphics for the description and recording of aortocoronary bypasses. AB - In the process of drawing up a computerized operation reporting system, a nomenclature for the precise description of recently fitted or existing aortocoronary bypasses has been developed. This is based on a sequence of letters showing in one line which type of bypass has been fitted, the graft material used, the central anastomosis (source) as well as the peripheral anastomoses on the coronary arteries (objective). For this purpose, abbreviations of the customary terms in use in cardiac surgery have been used. A computer graphics programme has been created in parallel, enabling all bypasses (existing and/or new) to be sketched into the diagram of a heart with the aid of a mouse. The bypass nomenclature is automatically generated from the diagram, which can also be printed out as a sketch of the operation. The complete diagram of the heart plus data input forms enable the operation report to be compiled automatically. The nomenclature and the graphics programme are easily learnt, simplify work, can readily be incorporated into a computerized hospital organization and enhance documentation quality. PMID- 1931096 TI - [Dizziness: a frequent complaint in neurology consultation]. PMID- 1931097 TI - [Correlation between magnetic resonance and disability scales (EDSS and ISS) in multiple sclerosis]. AB - In the present study the lesions in MRI imaging were quantified and compared with the clinical and functional abnormalities in 56 patients (27 females and 29 males) with definite multiple sclerosis (MS). The evolution was relapsing in 30, there were relapses followed by progressive evolution in 10, and evolution was progressive from the onset in 16. A good correlation was found between the disability scale EDSS and total lesions in MRI (r = 0.45), and also with the disability scale EDSS and hemispheric (r = 0.45) and centrioval (r = 0.41) involvements and with lesions near the third ventricle (r = 0.32). The clinical parameters predicting a greater surface of involvement in MRI were late onset (beyond 45 years) and progressive evolution. The best correlation between disability scale and MRI lesions was found between EDSS and periventricular (lateral ventricles) lesions (r = 0.46). The linearly correlation between both disability scales was good (r = 0.86), but it improved when an exponential equation was used (r = 0.91). This could allow to use the more simple scale (ISS) with a mathematical transformation. When the patients with a greatest surface of involvement were compared with the remaining MS patients, significant differences were found for nearly all evaluated disability items. Patients with greater involvement surfaces in MRI had greater disability. PMID- 1931098 TI - [Changes in the Q-Tc interval in the acute phase of cerebral ischemic infarction]. AB - A clinical prospective study was carried out in 100 patients with stroke (S) (56 with lacunar infarctions [LI] and 44 with nonlacunar infarctions [NLI]) and in a control group without organic cerebral disease (n = 100) to compare the abnormalities in the Q-Tc interval of the electrocardiogram. An abnormal Q-Tc interval (greater than 0.44 sec) was found in 18% of S and in 8% of the control subjects (p less than 0.05). These abnormalities in S were more common at the onset of the disease (18%) than from 3 weeks after the development of focal signs (9%). An abnormal Q-Tc interval was found in 18% of NLI (8 of 44 cases) and in 18% of NLI (10 of 56 cases). Regarding the topography of the lesions, an abnormal Q-Tc interval was found in 20% (3 of 15 cases) of the brainstem infarctions; in 19% of the infarctions of basal ganglia (9 of 47 cases) and in 13% (4 of 30 cases) of hemispheral strokes. Our results show that the abnormalities of Q-Tc interval in strokes are not uncommon. They may be reversible and in some cases they are related with the topography of the cerebral lesion. PMID- 1931099 TI - [Adenine nucleotides in migraine]. AB - Several studies have shown that migraine is associated with an abnormal platelet activation state, characterized by increased plasma levels of platelet BTG and PF4 proteins. Adenine nucleotides are contained in platelets as a part of the dense granules released during platelet activation. In the present study we evaluated the plasma levels of the adenine nucleotides AMP, ADP and ATP during asymptomatic and painful episodes in a group of 50 patients with migraine (common and classical) and a control group. During the painful phases we found a significant reduction in AMP plasma levels, and we did not find significant differences between the control group and the migraine patients in ADP and ATP levels, nor between asymptomatic and painful phases. Our results support the hypothesis that in migraine a hyposecretion of platelet dense granules is present. PMID- 1931100 TI - [Neural regulation of insulin release]. PMID- 1931101 TI - [Dissecting aneurysm of the aorta and neurological manifestations]. PMID- 1931102 TI - [Episodic ++paroxysmal hemicrania or chronic paroxysmal hemicrania in pre-chronic state?]. AB - Two women suffered from strictly unilateral, periocular headaches for many years. The clinical characteristics of headaches were those described in chronic paroxysmal hemicrania. However, both patients showed an episodic evolution of pain. In one case, this stage could be considered pre-chronic because it was later followed by the classic and apparently definitive chronic period of the disorder. In the second case the episodic stage persisted all along the evolution of the disease and the headache did not reach the chronic period. The patient has been free of pain without treatment for the last three years. This second observation can be considered as an example of episodic paroxysmal hemicrania. In the episodic cases the response of pain to indomethacin can be difficult to be ascertained. PMID- 1931103 TI - [Our experience with Kufs disease: familial form and sporadic case]. AB - Our experience on Kufs' disease includes a familiar, neurovisceral form and a sporadic case. The familiar form shows an autosomal, dominant inheritance, and belongs to Berkovic's type B. A variability on the age of onset was observed, being more protracted in women. The sporadic case belongs to Berkovic's type A. Her EEG showed a periodic, short-interval, activity for a long period of illness. NMR findings were nonspecific for the diagnosis. All cases showed granular osmiophilic deposits, but not storage characterized by fingerprint profiles. Visceral storage in many cases on Kufs' disease suggests the utility of visceral biopsy evaluation for the diagnosis during life. PMID- 1931104 TI - [Cranial multineuritis caused by the varicella-zoster virus without cutaneous lesion]. PMID- 1931105 TI - [Deafness in Mills syndrome]. PMID- 1931106 TI - [Perimesencephalic hemorrhage: a benign form of subarachnoid hemorrhage]. PMID- 1931107 TI - [Recurrent Miller-Fisher associated with non-defined systemic disease]. PMID- 1931108 TI - [Ventricular relaxation and distensibility. Echocardiographic and Doppler assessment]. PMID- 1931109 TI - [Morphologic course of the left ventricle after renal transplantation. Echocardiographic study]. AB - OBJECTIVE: To characterize and to quantitate the morphologic changes in left ventricle, in renal transplant patients (Pts) treated with cyclosporine, through sequential echocardiographic examinations. DESIGN: A prospective study of renal transplant patients, between October/88 and May/89, who maintained good function of the renal graft during the follow-up. SETTING: Cardiology and Nephrology departments of Santo Antonio Hospital. MATERIAL AND METHODS: 20 patients, 13 men and 7 women, mean age of 33 +/- 10, ranging from 20 to 56, constitute the final group of the study. These patients have been receiving dialysis during 3.8 +/- 2.3 years (0.4-8). Seven patients were excluded, five by echocardiographic criteria and another two because of chronic renal graft disfunction (creatinine greater than 2.0 mg%). The echocardiographic examinations were performed during the first week, and 1, 2, 3, 6 and 12 months after renal transplantation. The following measurements were performed: left ventricular end-diastole diameter (LVED), interventricular septal thickness (IVST), posterior wall thickness (PWT) and left ventricular mass index (LVMI). The measurements were obtained in M-mode following the conventional recommendations. Average values of at least 3 cardiac cycles were used. Heart rate, blood pressure, creatinine, hematocrit, body surface area and fistula patency, were determined at the time of each echocardiogram. MAIN RESULTS: The LVED decreased progressively until the third month, from 51.9 +/- 7 mm to 47.8 +/- 6 mm (p less than 0.001), remaining stable thereafter. The baseline value of IVST, 13.6 +/- 5 mm, was similar at the twelfth month, 13.8 +/- 2 mm (ns). The baseline value of PWT, 13.7 +/- 4 mm, decreased gradually since the second month, having reached 12.7 +/- 2 mm at the twelfth month (ns). The LVMI (g/m2) reduced progressively, from 243 +/- 82 to 190 +/- 38 at the end of the study (p less than 0.05. A high incidence of arterial hypertension was detected during the follow-up period; at the twelfth month, 18 patients (90%) were on antihypertensive drug therapy, 11 of which had blood pressure greater than or equal to 160/95 mmHg. CONCLUSIONS: We verified, one year after the renal transplantation, a significant decrease of LVMI, that was mainly determined by the LVED reduction. Left ventricular walls thickness had no significant variation; we think that the high incidence of hypertension during the follow-up period, in part due to the pressure effect of cyclosporine, may have been responsible for this fact. PMID- 1931110 TI - [Pressure response to dynamic exercise and antihypertensive therapy]. AB - OBJECTIVES: To study the exercise systolic pressure (SP) in hypertensive patients, its relation with left ventricular (LV) mass and the efficacy of its control by some antihypertensive drugs. DESIGN: To study the echocardiogram (ECHO) and exercise test (ET) in hypertensives (HT), before and after rest blood pressure (BP) control. SETTING: Out-patient cardiology clinic in a military hospital. METHODS: 53 male moderate HT, 30 to 60 years old, without other pathology, were studied with ECHO and ET. 28 HT repeated ET after rest BP control: Group A--Diuretic (Hchlt/Triam), n: 7; Group B--Atenolol, n: 10; Group C -Nifedipine, n: 11. RESULTS: 1. There was a positive correlation between LV mass index and exercise SP (r: 0.37; p less than 0.01), but not rest blood pressure. 2. Exercise test duration was increased only in group C. 3. Hypertensives with rest BP control had also normal exercise SP in group B, but not in groups A or C (Qui2: 11 735; p less than 0.001). CONCLUSIONS: 1. Exercise systolic blood pressure seems to be more important than rest blood pressure to the development of LVH in hypertensive patients. 2. The observed increase of exercise capacity in Nifedipine group must be considered in the treatment of physically active hypertensives. 3. Hypertensives with rest BP controlled by Atenolol have also, very probably, a normal exercise systolic pressure. 4. In physically active HT with rest BP controlled by Diuretic or Nifedipine may be useful an exercise test to evaluate exercise systolic pressure. PMID- 1931111 TI - [Myocarditis in early childhood. Two years' experience at the pediatric cardiology unit at the S. Joao Hospital]. AB - OBJECTIVE: The authors studied 14 children with myocarditis in order to correlate clinical and laboratorial data with evolution. DESIGN: Retrospective study of all cases with myocarditis admitted during a 2 year period. SETTING: Unidade de Cardiologia Pediatrica do HSJ. PATIENTS: 14 patients, aged 7 to 34 months, with the diagnosis of myocarditis on the ground of biopsy or necropsy findings. The clinical data analysed were: medical history, physical examinations, hematological and biochemical studies, chest X ray, electro and echocardiogram, virus and immunological studies and cardiac catheterization. RESULTS: All the patients had congestive heart failure and 10 had a history of a previous viral infection. Those who survived the first week were submitted to hematological and biochemical studies, chest X Ray, electrocardiogram, echocardiogram, virological and immunological studies and cardiac catheterization. All patients were treated with captopril and furosemide, 11 received dobutamine and 6 an immunosuppressive regime. Six patients died in the first week and one, nine months after diagnosis. One patient had an unfavourable course and the other six improved clinically. CONCLUSIONS: The authors were not able to find any correlation between laboratorial data and the disease outcome. Age less than one year and an abrupt onset were associated with 100% mortality. Immunosuppression was associated with improvement in 66% of the patients. PMID- 1931112 TI - [Cardiac amyloidosis. Diagnostic and prognostic value of Doppler echocardiography]. AB - We report two cases of cardiac amyloidosis. The echocardiographic features of this infrequent disease, and the doppler study of the ventricular diastolic function in these patients, together with its possible prognostic significance, is revised. PMID- 1931113 TI - [Relaxing and constricting factors derived from vascular endothelium]. AB - The Author summarizes the factors produced in vascular endothelium in response to different stimuli. The relaxing factor is identified as nitric oxide, a radical, whereas the constricting factor, endothelin, is a peptide. Their actions are related to several situations, both normal and pathologic, still poorly understood. PMID- 1931114 TI - [Equilibrium radionuclide angiography after inotropic stimulation in the assessment of functional reserve of the left ventricle]. PMID- 1931115 TI - [Effort radionuclide angiography in the assessment of the surgery outcome of aorto-coronary bypass]. PMID- 1931116 TI - [Integrating molecular biology in clinical cardiology: a great challenge, a big promise]. PMID- 1931117 TI - [Ambulatory monitoring of blood pressure. Validation of a method]. AB - Before the routine use of our ambulatory blood pressure (ABP) device, we did the correlation analysis of 153 pairs of blood pressure measurements within the ABP and gold-standard sphygmomanometer. We got a good correlation but a systematic statistical error about less 7 mmHg on systolic measurement and 11 mmHg on diastolic measurement by the ABP device. The different qualities found among the devices that we have in the market, lead to the proposal of protocols of validation in the premarketing and periodic quality assessment by the clinics. PMID- 1931118 TI - [Value of ventricular geometry in the evaluation of direct ventricular pressure]. AB - OBJECTIVE: To determine the echocardiographic end-systolic ventricular geometry value in evaluating right ventricular systolic pressure (RVSP). MATERIAL AND METHODS: We studied prospectively 68 patients (mean age = 6.0 +/- 5.0 years), submitted to cardiac catheterization for cardiac disorders not involving left ventricular (LV) outflow tract obstruction, within 24 hours after two-dimensional echocardiographic (2D echo) examination. 2D echo evaluation of RVSP was performed using end-systolic LV transverse orthogonal diameters (TDR). The LV transverse orthogonal diameters (antero-posterior and supero-inferior) were measured on a parasternal short-axis image, at the tips of papillary muscles. 2D echo semi quantitative evaluation of RVSP was tested correlating TDR with hemodynamic RVSP/LV systolic pressure (LVSP) ratio--group 1. We also used regression equation derived from the first 35 patients to quantify RVSP in the last 33 patients- group 2. In these cases, systolic systemic arterial pressure measured by sphygmomanometry was taken as LVSP. RESULTS: The TDR ranged from 1.0 to 2.1 (mean = 1.5 +/- 0.3) and the RVSP/LVSP ratio from 0.3 to 1.7 (mean = 0.7 +/- 0.4). All patients with RVSP/LVSP greater than or equal to 65% have TDR greater than or equal to 1.3 and when RVSP less than or equal to 35 mmHg we always obtained TDR less than or equal to 1.2. The correlation between 2D echo estimated and catheter measured RVSP shows, for group 1, r = 0.88 and y = 1.1X-0.88 and, for group 2'. r = 0.88. CONCLUSION: In the absence of LV systolic obstruction, TDR is a reliable non invasive method in evaluating the RVSP. PMID- 1931119 TI - [Methodology of studies of myocardial perfusion]. PMID- 1931120 TI - [Myocardial perfusion with isonitriles]. PMID- 1931121 TI - [Indications for myocardial perfusion scintigraphy with thallium-201 in the evaluation of the coronary patient]. PMID- 1931122 TI - [Tomographic quantification in myocardial scintigraphy with thallium]. PMID- 1931123 TI - [Lung thallium-201 uptake as an index of left ventricular function]. PMID- 1931124 TI - [Myocardial perfusion in the evaluation of post-infarct and post-thrombolysis residual ischemia]. PMID- 1931125 TI - Binding mode of azide to ferric Aplysia limacina myoglobin. Crystallographic analysis at 1.9 A resolution. AB - The binding mode of azide to the ferric form of Aplysia limacina myoglobin has been studied by X-ray crystallography. The three-dimensional structure of the complex has been refined at 1.9 A resolution to a crystallographic R-factor of 13.9%, including 126 ordered solvent molecules. Azide binds to the heme iron, at the sixth co-ordination position, and is oriented towards the outer part of the distal site crevice. This orientation is stabilized by an ionic interaction with the side-chain of Arg66 (E10) which, from an outer orientation in the 'aquo-met' ligand-free myoglobin, folds back towards the distal site in the presence of the anionic ligand. In the absence of a hydrogen bond donor residue at the distal E7 position in Aplysia limacina myoglobin, a different polar residue, Arg66 at the E10 topological position, has been selected by molecular evolution in order to grant ligand stabilization. PMID- 1931126 TI - Binding of the neuroleptic drug haloperidol to a monoclonal antibody: refinement of the binding site molecular model using canonical structures. AB - The ligand binding site of a monoclonal antibody (185), which binds the neuroleptic drug haloperidol, has been modelled using canonical structures and energy minimization techniques. This refined modelling protocol has allowed us to predict the variable region loop conformations. Three key residues, H:50(W), H:100a(D) and L:96(Y) appear to create the basis of the electrostatic, pi-pi stacking interactions and hydrogen bonding required for the high affinity binding site characteristics present in this antibody. The use of computer-aided graphics techniques and appropriate three-dimensional modelling permits inspection of the predicted molecular recognition features of the ligand binding site. PMID- 1931127 TI - [A new working method: our experience]. PMID- 1931128 TI - [How to find information in the Index to Dental Literature]. PMID- 1931129 TI - [Advances in the diagnosis and treatment of juvenile periodontitis]. PMID- 1931130 TI - A Pseudomonas aeruginosa alginate-exotoxin A conjugate that elicits anti-alginate and exotoxin A-neutralizing antibodies. AB - Pseudomonas aeruginosa alginate was covalently coupled to exotoxin A by reductive amination using adipic acid dihydrazide as spacer. The conjugate was composed of 25% alginate and 75% exotoxin A and possessed an average molecular mass higher than 700 kDa as determined by polyacrylamide gel electrophoresis. The conjugate had virtually no ADP-ribosyltransferase activity and a reduced cytotoxicity for TSA8 murine cells, derived from Friend erythroleukemia cells, as indicated by a greater than 50-fold increased LD50. Anti-conjugate antibodies recognized exotoxin A and alginate. A booster injection resulted in markedly increased antibody ELISA titers to both exotoxin A and alginate. The antibodies neutralized the exotoxin A toxicity. PMID- 1931131 TI - Conjugation of capsular polysaccharide to alpha-haemolysin from Staphylococcus aureus as a glycoprotein antigen. AB - The capsular polysaccharides of two pathogenic strains of Staphylococcus aureus 8914 and 31 were isolated and purified. These polysaccharides were conjugated to alpha-haemolysin prepared from the same strains. Amongst the various coupling procedures which were tested the best results were obtained with sodium cyanoborohydride and glutaraldehyde. The conjugates were purified and their immunologic properties were tested. They gave a positive response against antisera from whole bacterial cells. PMID- 1931132 TI - Rapid serodiagnosis of human mycobacteriosis by ELISA using cord factor (trehalose-6,6'-dimycolate) purified from Mycobacterium tuberculosis as antigen. AB - IgG antibodies against purified cord factor (trehalose-6,6'-dimycolate, TDM) in sera of 99 patients infected with mycobacteria (42 patients with tuberculosis excreting tubercle bacilli in the sputum, 11 patients with non-tuberculous mycobacteriosis excreting acid-fast bacilli in the sputum, and 46 patients without bacilli in the sputum but diagnosed as having pulmonary tuberculosis by chest X-ray films and physical examination), five patients with lung cancer, and 100 healthy controls which included subjects positive and negative for the tuberculin test were tested by the ELISA with TDM purified from Mycobacterium tuberculosis H37Rv as the antigen. Of the 99 cases of mycobacteriosis, 83 patients (83.8%) had positive results (48 samples from 53 patients, or 90.5%, with bacilli in the sputum, and 35 samples from 46 patients (76%) with tuberculosis diagnosed clinically). The sera of the five patients with lung cancer and the 100 controls all gave negative results. Thus, the sensitivity and specificity were 83.8% and 100%, respectively. ELISA with TDM as the antigen is simple, reproducible, and useful for the rapid serodiagnosis of general mycobacterial infections including tuberculosis, because it does not involve the cultivation of bacteria. PMID- 1931133 TI - Klebsiella pneumoniae glycoprotein RU-41740 enhances resistance of mice against Mycoplasma arthritidis-induced arthritis. AB - The effect of a purified glycoprotein extract from Klebsiella pneumoniae with non specific immunostimulating properties (RU 41740) on the development and course of mycoplasma arthritis was investigated. Male A/J mice aged 2-3 months were given RU-41740 either intraperitoneally (i.p.) or orally prior to injection with Mycoplasma arthritidis. RU-41740 injected i.p. at 0.1 mg kg-1 or given orally at 1 mg kg-1 prior to the infection and subsequently on alternate days enhanced the resistance of mice to mycoplasma arthritis (P less than 0.001). Doses of 1 mg kg 1 i.p. or 10 mg kg-1 orally did not modify the course of the arthritis significantly, probably due to immunosuppressive factors from monocytes. It is suggested that RU-41740 protects the mice by stimulating macrophages. This immunostimulant might prove useful in the treatment of mycoplasma diseases, especially in the immunocompromised host. PMID- 1931134 TI - Loss of cellular immune reactivity during acute Plasmodium falciparum malaria. AB - Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria transmission season 5 months prior to the attack, were included in the study. Lymphoproliferative responsiveness to purified soluble malarial antigens and to the unrelated antigen PPD was lost during the acute phase of the disease in most donors, but was regained during convalescence, except in four donors recrudescing or reinfected by day 30. In contrast to the suppression of antigenic responses, cellular responses to phytohaemagglutinin (PHA) remained virtually unaffected. All donors showed elevated plasma-levels of soluble IL-2 receptor during the acute phase of the disease which normalized during convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due to homing of this cell-population to lymphoid tissues. It was also found that acute-phase plasma was suppressive to PPD-induced proliferative responses, indicating an additional suppressive mechanism operating in vivo. PMID- 1931135 TI - Requirement of the conformational stability of a Salmonella ribosomal vaccine for its mouse protection. AB - The 43-kDa non-O antigenic component isolated from the crude ribosomal fraction of Salmonella typhimurium [9] was further purified by affinity chromatography (43 kDa protein: 43-kDp). Immunization with 43-kDp did not induce complete mouse protection in CF1 mice to 500 LD50 of S. typhimurium, although it elicited a substantial IgG antibody response. The 43-kDp exhibited the mitogenicity to splenocytes (CF1 and C3H/HeJ) and B cell-rich populations (CF1). Complexing 43 kDp with the compact ribosomes of Streptococcus pyogenes by formaldehyde (complex vaccine: CV) elicited both IgM and IgG antibodies to 43-kDp. CV induced a boosting effect to enhance IgG antibody response. Moreover, CV generated delayed type hypersensitivity to salmonella antigens and also conferred complete protection against 500 LD50 challenge of S. typhimurium to CF1 mice. These abilities of CV were reduced or impaired by RNase digestion. CV was able to induce partial or complete protection in inbred mouse strains (C3H/HeN, C3H/HeJ, DBA/2 and A/J). These data, in addition to other reports, suggest that conformational stability between ribosomes and contaminating substances such as 43-kDp or O-antigens might be required for the overall effects of the ribosomal vaccine. PMID- 1931136 TI - The wall of bacteria serves the roles that mechano-proteins do in eukaryotes. PMID- 1931137 TI - The biology of colicin M. AB - This communication summarizes our present knowledge of colicin M, an unusual member of the colicin group. The gene encoding colicin M, cma, has been sequenced and the protein isolated and purified. With a deduced molecular size of 29,453 Da, colicin M is the smallest of the known colicins. The polypeptide can be divided into functional domains for cell surface receptor binding, uptake into the cell, and killing activity. To kill, the colicin must enter from outside the cell. Colicin M blocks the biosynthesis of both peptidoglycan and O-antigen by inhibiting regeneration of the bactoprenyl-P carrier lipid. Autolysis occurs as a secondary effect following inhibition of peptidoglycan synthesis. Colicin M is the only colicin known to have such a mechanism of action. Immunity to this colicin is mediated by the cmi gene product, a protein of 13,890 Da. This cytoplasmic membrane protein confers immunity by binding to and thus neutralizing the colicin. Cmi shares properties with both immunity proteins of the pore forming and the cytoplasmically active colicins. Genes for the colicin and immunity protein are found next to each other, but in opposite orientation, on pColM plasmids. The mechanism of colicin M release is not known. PMID- 1931138 TI - The susceptibility of conjugative resistance transfer in gram-negative bacteria to physicochemical and biochemical agents. AB - Over thirty years of studies have established that conjugative transfer of plasmid-encoded resistance to drugs and heavy metals can take place at high frequency between various organisms under laboratory conditions. The detected transfer frequencies in soil, in aquatic environments, and in the urogenital and respiratory tracts of healthy animals and man have generally been low. However, the conversion of bacteria from susceptible to resistant to antibiotics has been observed often during antimicrobial therapy. This has formed a challenge for the antibacterial treatment of pathogenic bacteria and called for the evaluation of the extent of conjugative transfer in various environments. Several biochemical and physicochemical factors inhibit conjugation, show preferential toxicity against plasmid-bearing cells, or stimulate plasmid curing. These factors include various agents such as detergents, anesthetics, mutagens and antibiotics which affect membrane potential, membrane permeability, protein synthesis and the processing of DNA. The application of the data on these agents, summarized in this review, might be helpful in preventing drug multi-resistance from spreading. Also these data might be valuable in studies which use conjugation as a tool or which treat the molecular mechanisms involved in conjugation. PMID- 1931139 TI - Severity of angiographically proven coronary artery disease predicts smoking cessation. AB - We investigated the relationship between the extent of coronary artery disease (CAD) and the likelihood of cigarette smoking cessation in a population of 84 smokers between 21 and 75 years of age undergoing elective or urgent coronary angiography at the University of Massachusetts Medical Center. The smokers were enrolled in a pilot study investigating the relationship of hospitalization and coronary arteriography for coronary artery disease to subsequent smoking cessation and were scored at baseline as having none, one-, two-, or three-vessel disease. Smoking status at a mean follow-up time of 11 months was obtained by telephone interview, at which point 50% reported not smoking. Logistic regression showed a significant relationship between smoking cessation and two factors: the anatomic extent of CAD and the experience of having had coronary artery bypass surgery or percutaneous transluminal coronary angioplasty following the initial catheterization. We discuss the relative roles of patient knowledge and motivation and physician intervention, and their implications for smoking cessation interventions. PMID- 1931140 TI - The Comprehensive Prevention Knowledge and Applications Survey Instrument: its validity and reliability. AB - Because the instruments used to measure current practices among primary care physicians in a broad range of prevention activities are limited, we developed a study to test a tool that would evaluate current prevention knowledge and applications, including items regarding activities to prevent AIDS and other sexually transmitted diseases. The Comprehensive Prevention Knowledge and Applications Survey Instrument measures knowledge, counseling capabilities, and use of recommended applications in preventive medicine. We designed and tested a 74-item instrument. Four recognized experts in preventive medicine and public health determined its content validity. We then proceeded with reliability testing with a random sample of 315 family physicians and replicated it with an additional 432 physicians for stability reliability. Internal consistency reliability and stability reliability have both been demonstrated for this instrument. PMID- 1931141 TI - A survey of physicians' knowledge and application of AIDS prevention capabilities. AB - Currently, no effective immunization prevents AIDS and no curative treatment exists for the AIDS patient. However, sufficient knowledge of the pathophysiology of this disease exists to prevent its spread. Effective application of this capability requires that health care providers secure and apply this knowledge. This study reports the results of a national survey of family physicians' knowledge and application of AIDS prevention capabilities. The Comprehensive Prevention Knowledge Applications Survey Instrument was used for the survey. It revealed that, in contrast to other prevention activities, respondents (n = 765) reported low use of practices important in AIDS prevention. For example, only 18% routinely obtain sexual histories from patients seen regularly, and, of those obtaining these histories, fewer than 20% routinely obtain information regarding high-risk activities. Over 40% do not routinely ask about homosexual activities, and almost 60% omit questions about intravenous drug use, even though the patient has symptoms suggesting AIDS in both instances. Methods of enhancing application of available capabilities may focus on expanded education and intervention activities. PMID- 1931142 TI - Sexual self-defense versus the liaison dangereuse: a strategy for AIDS prevention in the '90s. AB - The present public health strategy to encourage the adoption of "safe sex" practices to contain the AIDS epidemic in America is incomplete. Current policy is responsive to and appropriate for control of homosexual, but not heterosexual transmission. Powerful societal forces restrict a woman's perception of risk. Consequently, the adoption of safe sex (condom use/insistence on use) by women at risk has not matched safe sex practice by homosexual men. Predictably, pattern two (heterosexual, maternal-fetal) HIV transmission is now rapidly increasing in the United States, particularly among minority women. In anticipation of an intensified pattern two subepidemic, AIDS containment policy should be reoriented to develop the role of women in AIDS prevention. An initiative, termed "sexual self-defense" (SSD), combines the technology of double-barrier (female irrespective of male) protection with a "universal precautions" approach to long term sexual risk management. The initiative addresses both per-contact infectiousness and new partner acquisition, the principal determinants of HIV spread. As a female-targeted strategy, SSD is a timely supplement to existing programs, consistent with the direction of contemporary women's movements in the United States. A "street smart" approach, SSD bridges ethnic and socioeconomic individual differences. As a unifying philosophy of risk management in health promotion, SSD may avert the threatened fragmentation of AIDS control from existing programs of sexually transmitted disease control and teenage pregnancy prevention. PMID- 1931143 TI - Baseline characteristics of participants in the Physicians' Health Study: a randomized trial of aspirin and beta-carotene in U.S. physicians. AB - The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial of primary prevention designed to assess the effects of low-dose aspirin on cardiovascular disease and of beta-carotene on risks of cancer. A total of 22,071 U.S. male physicians 40 to 84 years of age were randomized to one of four treatment groups: active aspirin and active beta-carotene, active aspirin and beta-carotene placebo, aspirin placebo and active beta-carotene, or both placebos. Whereas the beta-carotene component of the trial is ongoing, the blinded aspirin component was terminated early primarily because of a statistically extreme benefit of aspirin on first myocardial infarction. We obtained data relating to a large number of variables, including demographics, personal medical history, family history, health habits, and diet before randomization and compared them among the four treatment groups. As expected in a randomized trial of this sample size, the distribution of baseline characteristics was virtually identical among the treatment groups. This comparison indicates certainly no confounding by the baseline variables that were collected and suggests that other unmeasured or unknown potential confounders are also likely to be distributed evenly between the treatment groups. Thus, any observed differences in outcome between these groups likely result from the effects of the treatments themselves. PMID- 1931144 TI - Prevalence of behavioral risk factors in two American Indian populations in Montana. AB - Despite great improvements in recent decades, the health status of American Indians continues to lag behind that of other Americans. Continued health improvement will depend largely on changes in individual behavior. However, few data exist on health risk behaviors among American Indians. We used face-to-face interviews to estimate the prevalence of some of these behaviors among American Indians 15-49 years of age in two Montana locations: on the Blackfeet Reservation and in Great Falls. The prevalence of several important health risk behaviors was higher in these populations than in adult Montana residents in general. Tobacco use was very prevalent. Fifty percent of on-reservation women, 62% of off reservation women, 34% of on-reservation men, and 63% of off-reservation men were smokers at the time of the survey. Thirty-three percent of reservation men used smokeless tobacco. Other risk behaviors of high prevalence included acute heavy drinking (26% to 42% of men); overweight (29% to 41% of females); sedentary lifestyle (46% to 62% of all respondents); and nonuse of seat belts (64% to 79% of all respondents). Tribal leaders and the Indian Health Service are using the survey results to reduce the prevalence of behaviors harming the health of Indian people. In addition to providing valuable information about the surveyed populations, the survey served as a pilot for subsequent surveys of other American Indian groups. PMID- 1931145 TI - Smoking prevalence in the United States and Taipei City, Taiwan. AB - Although there are extensive antismoking efforts in the United States, smoking is a largely ignored health issue in Taiwan. In fact, tobacco advertising has increased dramatically since U.S. tobacco was first imported in 1987. We compared estimates of smoking prevalence of 83,281 Americans and 5,023 persons in Taipei, Taiwan, in 1986-1988. Among men, current smoking prevalence was higher in Taipei (49%) than in the United States (29%). In contrast, former smoking prevalence among men was substantially lower in Taipei (5%) than in the United States (32%). Young adults and those with lower and middle education levels had the highest smoking prevalence in both surveys. Among women, the current smoking prevalence was only 8% in Taipei, compared to 25% in the United States. The former smoking prevalence among Taipei women (1%) was also lower than among U.S. women (18%). Our findings indicate the need for expanding antismoking efforts in Taiwan, especially among men and among persons with lower and middle education levels. PMID- 1931146 TI - Postneonatal deaths from infections and injuries: race, maternal risk, and age at death. AB - Most infants with birthweights greater than or equal to 2,500 g who survive the first 27 days of life have a reasonable opportunity to grow into healthy children. However, some of these infants succumb to two potentially preventable causes of death: infections and injuries. Although the relationship between maternal attributes and risk of death from these causes has been described, little is known about how maternal attributes relate to postneonatal age at death. To examine this relationship, we analyzed postneonatal deaths from infections and injuries among 3,116,391 white and 638,915 black neonatal survivors with birthweights greater than or equal to 2,500 g. We grouped postneonates by maternal race and risk status. Infants of mothers greater than or equal to 20 years of age who started prenatal care in the first trimester were considered low risk; all others were high risk. For each category of infection death (respiratory, central nervous system, and other bacterial--including sepsis), neither race nor maternal risk status was related to age at death. The same was true for three categories of injury death (motor vehicle, fire, and homicide), but not for injury deaths in the category of choking, drowning, or suffocation. Among blacks, these deaths occurred at younger ages, regardless of maternal risk status. Thus, efforts to prevent deaths from choking, drowning, or suffocation among blacks should focus on early infancy. PMID- 1931147 TI - Shifts in medical student beliefs about AIDS after a comprehensive training experience. AB - We evaluated the beliefs of second-year medical students regarding critical issues in the AIDS epidemic before and after an intensive two-day training symposium. Paired responses, collected for three consecutive years, were available for 187 students. Our results indicate that, although the students generally held progressive beliefs on prevention and public policy prior to training, a significant minority held views that differ from expert opinion. After the training experience, we observed substantial shifts of opinion on several issues. For example, among those who initially believed that physicians should record results of HIV testing in patient charts without patient permission, 45% shifted to disagreement. On mandatory premarital testing, 43% of those initially supporting it shifted to disagreement. On some issues, such as contact tracing, where expert opinion is less clear, student opinion moved very little overall. Over the three-year period, we found evidence of a trend towards less concern over HIV transmission to men from causal sex with infected female partners and a trend towards acceptance of glove-wearing when handling all blood specimens. In conclusion, we demonstrate that the beliefs of medical students concerning difficult issues posed by the AIDS epidemic can be changed substantially in the short-term by a specially designed intensive educational program. Reinforcement and persistence of these changes should now be a concern for medical educators. PMID- 1931148 TI - Regaining the preventive medicine edge: training for 2000 and beyond. AB - We review the state of preventive medicine in the context of four factors that have eroded the influence and effectiveness of the specialty: (1) historical; (2) cultural; (3) political-economic; and (4) changing epidemiological and demographic factors. We address the implications for public and medical peer recognition of preventive medicine, for funding of residency programs, and for recruitment of medical students. We outline five objectives for preventive medicine training as steps to improve the response of the specialty to the above factors and to regain its edge. Also, we propose two specific innovative training programs to partially meet these objectives: a cross-cultural public health exchange and a preventive medicine fellowship in policy and public administration. We discuss the pertinence of these programs in terms of reversing preventive medicine's growing obsolescence. PMID- 1931149 TI - Erythrocyte membrane fluidity and changes in plasma lipid composition: a possible relationship in childhood obesity. AB - We have studied plasma lipid patterns and erythrocyte membrane fluidity in 60 obese children and 20 normal children. Plasma levels of total cholesterol and associated low-density lipoproteins were significantly increased in 20 obese patients with respect to controls. A significant decrease in membrane fluidity, measured as an increase in the fluorescence polarization value of the probe 1,6 diphenyl-1,3,5-hexatriene, associated with an increase in the cholesterol/protein ratio has been shown in obese patients. The study of the correlation between erythrocyte membrane fluidity and plasma cholesterol has indicated that significant changes in fluidity and membrane lipid composition also occur in erythrocytes of obese patients with normal plasma lipid levels. These findings confirm that the erythrocyte membrane responds very early to modifications of plasma lipoproteins and suggest that in childhood obesity a modified transfer of cholesterol from plasma to erythrocyte membrane may take place. PMID- 1931150 TI - Products of lipid peroxidation and changes in sulfhydryl compounds in pancreatic tissue of rats with caerulein-induced acute pancreatitis. AB - Acute edematous pancreatitis was induced in rats by iv infusion of caerulein (CR) in a supramaximal dose of 7.5 x 10(-6)g x kg-1 x hr-1 during 6 hr. The most important finding of our study was the marked decrease of protein and nonprotein thiol content in pancreatic tissue of rats with CR-induced acute pancreatitis (AP). Oxygen radicals as well as 4-hydroxyalkenals resulting from lipid peroxidation are believed to be at least partly responsible for this phenomenon. Covalent binding of excessive amounts of 4-hydroxyalkenals to pancreatic tissue protein sulfhydryl groups has been documented. Presented data suggest a serious disturbance of sulfhydryl compounds metabolism in pancreatic tissue of rats with CR-induced AP which may be of importance in the pathogenesis of the disease. PMID- 1931151 TI - Screening for cystic fibrosis: feasibility of molecular genetic analysis of dried blood specimens. AB - Direct genotypic analysis for the common Caucasian cystic fibrosis mutation (delta F508) was performed using dried blood specimens in a filter paper matrix (neonatal screening blotter). DNA was obtained from dried and liquid blood samples, amplified, and analyzed by polyacrylamide gel electrophoresis. Additionally, intact 4-mm-diameter punched discs from blotters containing dried blood specimen were used in the amplification reactions and analyzed by electrophoresis. The results agreed completely between these three sample types, demonstrating the feasibility of molecular genetic confirmation of the delta F508 mutation from the neonatal screening blotter among those with positive CF screening results. Such a program could reduce follow-up testing by at least 50% in a CF newborn screening program and would identify immediately those families who would benefit from carrier detection for the delta F508 allele. PMID- 1931152 TI - Purification and characterization of leucine-specific aminopeptidase from the soluble fraction of human placenta. AB - A soluble aminopeptidase distinct from two enzymes described previously was isolated from human placenta and some of its properties were investigated. The three aminopeptidases were separated by DEAE-cellulose chromatography. The newly found aminopeptidase exhibits specific hydrolysis of leucine derivatives among various synthetic substrates. However, a broad substrate specificity was observed toward some natural bioactive peptides. PMID- 1931153 TI - Incorporation of liposomal phytosterols into human cells in culture: a potential in vitro model for investigating pathological effects of phytosterolemia. AB - A potential in vitro cell culture model was developed for studies concerning the pathological effect of phytosterolemia in which liposomal phytosterols were incorporated into human skin fibroblasts and hepatoblastoma (HepG2) cells. After incubation with phytosterols, fibroblasts and HepG2 cells contained a significant amount (20-27%) of phytosterols (campesterol and beta-sitosterol). Phytosterol accumulation caused a significant reduction in the cholesterol content of cells. Labeled sitosterol and cholesterol showed similar uptake with lower esterification of sitosterol when compared to cholesterol. Labeled sitosterol incorporated into LDL was esterified to a greater extent than sitosterol added as straight liposome. About 23% of the labeled sitosterol was converted into acidic products and 5.6% was present as 5 alpha-stanols in HepG2 cells. PMID- 1931154 TI - Membrane-bound hemoglobin as a marker of oxidative injury in adult and neonatal red blood cells. AB - A comparative study of the effect of hydrogen peroxide on adult and neonatal red blood cell (RBC) membrane protein composition has been carried out. The results indicate that (a) the native neonatal RBC membranes contain higher levels of membrane-bound hemoglobin (MBHb) than the adult RBC membranes. (b) The content of MBHb increases when RBCs are incubated with increasing concentrations of hydrogen peroxide (H2O2), more so in neonatal than in adult RBCs; however, neonatal RBC membrane proteins are less susceptible to H2O2 oxidation than adult ones. This could be attributed to the fact that Hb F, which is more susceptible to oxidation than Hb A, adds to the reduction potential of neonatal RBC (in which it is present in large amounts) and partially protects neonatal membrane proteins against oxidant stress compared to Hb A in adult RBC. (c) In both neonatal and adult RBCs, Spectrin 1 is relatively more susceptible to oxidant stress than spectrin 2, and spectrins in adult RBC are more labile for peroxidation than the spectrins in neonatal RBC. (d) Based on electrophoretic studies with and without reduction of membranes with mercaptoethanol, we have classified two types of MBHb: Type I is adsorbed to membrane by noncovalent interactions and Type II MBHb is chemically crosslinked to membrane components by disulfide bridges; the content of both these types increases when RBCs are incubated with increasing concentrations of H2O2. (e) Band 6 protein is present in higher amounts in neonatal than in adult RBC membranes. (f) Since the total content of MBHb increases linearly with the level of oxidant stress, we suggest that it could be used as a marker for oxygen radical-induced injury to tissues. PMID- 1931155 TI - Autologous immunoglobulin-G binding to erythrocytes subjected to cyclical deoxygenation in vitro. AB - This study demonstrates that low-density metabolically replete HbSS erythrocytes suspended in heat-inactivated autologous plasma and subjected to 15 hr of cyclical deoxygenation (under nitrogen) bind significantly increased quantities of autologous IgG as compared with oxygenated paired samples. IgG binding to the erythrocyte surface was quantified by a nonequilibrium 125-iodinated protein A binding assay and by flow cytometry. Sickle cells deoxygenated 15 hr (37 degrees C) in the presence of 2 mM calcium bound 2.2 +/- 0.2 (mean +/- SD)-fold more IgG (p less than 0.01) than oxygenated paired samples. Sickle erythrocytes deoxygenated in 0.4 mM EDTA bound 1.7 +/- 0.3 (mean +/- SD)-fold more autologous IgG than oxygenated controls (p less than 0.05). Indirect immunofluorescence assays also demonstrated that the relative levels of autologous IgG bound to sickle cells after 15 hr cyclical deoxygenation in the presence or absence of calcium was increased as compared with IgG binding by oxygenated paired samples. After 3 hr of cyclical deoxygenation in the presence of 2 mM calcium sickle erythrocytes exhibited a 40-60% increase in IgG binding, as compared with 10-20% increased IgG binding by paired samples treated in EDTA. These findings demonstrate that repeated morphologic sickling will increase the IgG binding capacity of low-density sickle cells, and suggest that sickling-associated alterations of the cell surface will produce new binding sites recognized by autologous IgG. These studies also show that the sickling-induced increase in IgG binding may be slightly enhanced by the presence of extracellular calcium. PMID- 1931156 TI - Amino acids in the rat liver and plasma and some metabolites in the liver after sodium benzoate treatment. AB - The effect of sodium benzoate administration on amino acids in the liver and plasma and various metabolites in the liver was studied. Changes in glutamine and ornithine were noted only at a higher dose (10 mmol/kg body wt) of benzoate, whereas even a lower dose caused a significant decrease in glycine, serine, and alanine levels of plasma and liver. A dose- and time-dependent decrease in glycine levels was studied. A decrease of up to 50% in the glycine concentration may limit its own transport into mitochondria and availability for the formation of hippurate. A decrease in alanine may have resulted from stimulation of gluconeogenesis from alanine, by increased ammonia. Among the metabolites studied, ATP and acetyl-CoA decreased and ammonia increased significantly even at a lower dose (5 mmol/kg body wt) of benzoate. The compounds that require ATP for their synthesis such as N-acetylglutamate and glutamine decreased significantly only at the higher dose of benzoate, whereas urea and glutathione levels were unaffected under our experimental conditions. PMID- 1931157 TI - Generation of 3HOH from D-[6-3H]glucose by erythrocytes: role of pyruvate alanine interconversion. AB - Human and rat erythrocytes were found to generate 3HOH from D-[6(N)-3H]glucose. The rate of 3HOH production represented 7-10% of the glycolytic flux. The generation of 3HOH appeared attributable, in part at least, to the detritiation of [3-3H]pyruvate during the interconversion of the 2-keto acid and L-alanine in the reaction catalyzed by glutamate-pyruvate transaminase. Indeed, purified pig heart glutamate-pyruvate transaminase, as well as homogenates prepared from rat erythrocytes or pancreatic islets, catalyzed the generation of 3HOH from L-[3 3H]alanine. When the production of tritiated pyruvate from L-[3-3H]alanine was coupled to the conversion of the 2-keto acid to L-lactate, the production of 3HOH accounted for one-third of the reaction velocity, the latter failing to display isotopic discrimination. In these experiments, the production of 3HOH was abolished by amino-oxyacetate. Likewise, in intact rat erythrocytes, aminooxyacetate inhibited the generation of 3HOH and tritiated L-alanine from D [6-3H]glucose (or D-[1-3H]glucose), as well as the generation of 3HOH from L-[3 3H]alanine. In pancreatic islets, however, aminooxyacetate failed to affect significantly the generation of 3HOH from D-[6-3H]glucose. These findings indicate that the generation of 3HOH from D-[6-3H]glucose is mainly attributable to an intermolecular tritium transfer in transaminase reaction, at least in cells devoid of mitochondria. PMID- 1931158 TI - Phosphoglucoisomerase-catalyzed interconversion of hexose phosphates. A model for D-[2-3H]glucose metabolism in human erythrocytes. AB - When D-[2-3H]glucose 6-phosphate mixed with the unlabeled ester is converted to D [1-3H]fructose 6-phosphate and 3HOH in the phosphoglucoisomerase reaction and then to D-[1-3H]fructose 1,6-bisphosphate in the phosphofructokinase reaction, the specific radioactivity of the latter metabolite and the production of 3HOH relative to the total generation of tritiated end products are both inversely related to the concentration of phosphofructokinase. In human erythrocytes, the modeling of D-[2-3H]glucose metabolism, based on the activity of phosphoglucoisomerase in cell homogenates and on the steady-state content of D glucose 6-phosphate and D-fructose 6-phosphate in intact cells, indicates that the back-and-forth interconversion of these esters is about five-times higher than the net glycolytic flux. Yet, the production of 3HOH from D-[2-3H]glucose is about 20% lower than the net glycolytic flux, as judged from the production of 3HOH from D-[5-3H]glucose. Thus, an incomplete detriation of D-[2-3H]glucose is not incompatible with an extensive interconversion of hexose 6-phosphates in the reaction catalyzed by phosphoglucoisomerase. PMID- 1931159 TI - Enhancement of differentiation of rat adipocyte precursor cells by pertussis toxin. AB - To examine whether GTP-binding protein(s) is (are) involved in adipocyte differentiation, the effect of pertussis toxin (PT) was studied in rat adipocyte precursor cell culture. PT potentiated adipose conversion induced by dexamethasone, insulin, and 1-methyl-3-isobutylxanthine in a dose- and time dependent fashion. Attenuation of an inhibitory control of adenylate cyclase was not the mechanism of action of PT. The dose-dependent inhibition of PT-catalyzed ADP-ribosylation of the Mr 40,000 protein of the cell membrane by preincubation of the toxin was inversely related to the potentiating effect on differentiation. PT-sensitive G protein(s) may be involved in adipocyte differentiation in a negative fashion. PMID- 1931160 TI - Characterization of a novel biochemical abnormality in galactosemia: deficiency of glycolipids containing galactose or N-acetylgalactosamine and accumulation of precursors in brain and lymphocytes. AB - Classic galactosemia, an inborn error of human galactose metabolism, is characterized by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). The current model for the pathophysiology of this disease ascribes most of its symptoms to the toxicity of intracellular galactose 1-phosphate (Gal-1-P), one of the substrates of GALT which accumulates in the untreated disease state. Recently, a reduction in the intracellular concentration of UDP-Gal (uridine diphosphogalactose), one of the products of GALT, has been described in treated galactosemic patients. We investigated whether galactosemic patients might also have reduced amounts of those macromolecules that depend on UDP-Gal for their biosynthesis. We report a reduction in glycolipids that contain either galactose or its derivative N-acetylgalactosamine and an accumulation of the precursors to these compounds in the brain of a neonate with galactosemia. We also found an imbalance in glycolipids in galactosemic lymphoblasts. This novel biochemical abnormality observed in galactosemic patients is not addressed by dietary galactose-restriction therapy and could explain some of the chronic neurologic and other complications of galactosemia. PMID- 1931161 TI - [Regional cerebral blood flow in moyamoya disease using 123-I IMP-SPECT--follow up study before and after therapy]. AB - The recent development of a new radiopharmaceutical 123 I-isopropyl-p iodoamphetamine (IMP), which is taken up by the brain from the blood flow, has offered a possibility of constructing scintigraphy maps of regional cerebral blood flow (rCBF) using single photon emission CT. We evaluated the clinical utility of this method in moyamoya disease. Five patients with moyamoya disease, who were examined by IMP-SPECT before and after bypass operations, were selected. On the IMP images before operations, all patients showed focal or global decrease of rCBF. There was a good correlation between the area and degree of rCBF abnormalities and severity of clinical symptoms and stage on angiography. The area of rCBF decrease coincided with the dominant area of rebuild-up phenomena on EEG. On the IMP images just after operations, the rCBF changed for the worse transiently in three patients, and the crossed cerebellar diaschisis appeared in two patients. On the IMP images 3 months after operations, the rCBF increased in company with the improvement of clinical symptoms. The increased rCBF on the point of operation was recognized in two patients with good prognosis. These results suggest that IMP-SPECT is a noninvasive and useful method of assessing the effects of therapy as well as the characteristic hemodynamic abnormalities in moyamoya disease. PMID- 1931162 TI - [Neural plasticity after neonatal hypoxic and ischemic insult in rats]. AB - Rats with huge porencephaly occupying the left cerebral hemisphere were used for this study. Porencephaly was caused experimentally by the ligation of the left common carotid artery and subsequent hypoxic exposure at the age of 7 days. A large band of horseradish peroxidase (HRP) positive fibers was found crossing at the pyramidal decussation to reach the contra-lateral corticospinal tract and the deeper part of the funiculus, in the cervical cord. However, a small band of HRP positive fibers was noticed to reach the ipsilateral corticospinal tract without crossing at the pyramidal decussation. This result indicates that the developing pyramidal neurons in the right hemisphere carry the plasticity even after suffering from considerable hypoxia. PMID- 1931163 TI - [Early 123I-IMP SPECT in patients with epilepsy]. AB - Early single photon emission computed tomography (SPECT) using N-isopropyl-p [123I]iodoamphetamine (123 I-IMP) was performed in seventy-one patients with epilepsy admitted to Kanagawa Rehabilitation Hospital from July 1987 to February 1989; epilepsy and epileptic syndrome 27, encephalitis/encephalopathy 10, clinical Reye syndrome 3, cerebro-vascular disorders 8, sequelae of head trauma 4, cerebral palsy 5, brain anomaly 4, others 10. We classified these cases according to the 1989 criteria of the International League Against Epilepsy, and compared with the findings of the SPECT studies with the EEG and CT. In idiopathic epilepsy, the SPECT findings were within normal limits. Abnormal foci on EEG were not correlated with low uptake areas on SPECT. In the symptomatic epilepsy, especially in the West and Lennox syndromes, SPECT showed a decrease in diffuse cerebral cortical blood flow during ACTH therapy. This was also seen in some cases with normal CT imaging. The results suggest that the hemodynamic pathophysiology of the brain and the indications of therapeutic effectiveness in epilepsy are shown more accurately by SPECT than CT. PMID- 1931164 TI - [Cerebral blood flow velocities in the anterior cerebral arteries and basilar artery. II. Investigation in very low birth weight infants]. AB - We studied the values of the Pourcelot's index of resistance in the anterior cerebral artery (RI-ACA) and basilar artery (RI-BA) in very low birth weight infants weighing less than 1,500 g at birth. At the time of measurements, their postconceptional ages were 32, 34, 36, 38, 40 and 42 weeks. The mean value of RI ACA (0.744 +/- 0.026, +/- SD) was significantly lower than that of RI-BA (0.766 +/- 0.026) (p less than 0.001), and they were higher than those in normal term infants. However, the mean value of RI-ACA and RI-BA, averaged from the measurements of postconceptional ages at 38, 40 and 42 weeks, showed no significant difference from those of normal term infants. In contrast, the mean value of RI ratio (= RI-ACA/RI-BA) in very low birth weight infants showed no significant difference from that of normal term infants. PMID- 1931165 TI - [Deep white matter hyperintensity in occipital lobe on T2 weighted magnetic resonance imaging]. AB - Magnetic resonance imaging (MRI) was performed in 270 patients with various neurologic complaints (1-15 Y) with a 0.5 tesla superconducting imaging system (MRT-50 A, Toshiba Co.) using a field echo sequence (TR/TE: 300 ms/14 ms) and a spine echo sequence (TR/TE: 2,000 ms/100 ms or 2,000 ms/120 ms, and 2,000 ms/30 ms). The slice thickness was 10 mm. Hyperintensity areas on T2-weighted images were noted at the occipital lobe in 33 patients (12.2%). Twenty-seven of them had hyperintensity within the deep white matter, which revealed iso- or hypointensity on T1-weighted images. The diagnosis for the 27 patients included medulloblastoma after multidisciplinary therapy (1), congenital heart disease (1), neurofibromatosis (1), tuberous sclerosis (1), congenital muscular dystrophy (1), congenital myotonic dystrophy (2), febrile convulsion (2), autism (3), epilepsy (9) and unknown causes (6). Because the hyperintensity areas are age-dependent, they may result from delayed myelination in the central nervous system. PMID- 1931166 TI - [Clinical features of cases whose cerebral blood flow was preserved only in the basal ganglia region]. AB - In the series of our studies of positron emission tomography (PET), we had some cases whose cerebral blood flow was reduced in the cerebrum, cerebellum and brain stem, and was preserved only in the basal ganglia region. We studied their clinical features and electrophysiological findings of these cases. These 5 cases included neuronal ceroid lipofuscinosis, Krabbe disease, Tay-Sachs disease, progressive myoclonus epilepsy and subacute sclerosing panencephalitis. Clinically they showed symptoms associated with diffuse cerebral and brain stem involvements. Electrophysiological studies also revealed the involvements of cerebrum and brain stem. These 5 cases were classified to persistent vegetative state clinically. Vegetative state was considered to be heterogeneous concerning about cerebral metabolism. There may be one group presenting a peculiar cerebral metabolic condition described here in vegetative states. And this condition may be specific to some neurodegenerative or metabolic disorders that involve cerebellum and brain stem as well as cerebrum. PMID- 1931167 TI - [Two cases of ictal automatisms of frontal lobe origin]. AB - Two cases of ictal automatisms of frontal lobe origin are reported. Both two cases had automatisms characterized by abrupt onset and ending, short duration, preservation of consciousness and frequent attacks in cluster. The ictal manifestations included rocking of body and violent thrashing of limbs in prone position with loud screaming. No initial staring or postictal confusion was noted. Interictal EEGs showed spikes in the frontal area. Ictal EEGs began with attenuation of background activity and/or fast rhythmic waves dominant in the frontal area. Just after clinical seizures, high voltage slow waves in bilateral frontal areas and rhythmic alpha waves in the occipital areas were recorded. The EEG findings suggested that the paroxysmal activities were localized in bilateral frontal lobes, not spreading to the temporal lobe. PMID- 1931168 TI - [A case of brain infarction associated with viral encephalitis: MRI and pathological findings]. AB - A 10-year-old girl had an infarction in the left brain during an acute viral meningoencephalitis. She initially showed seizure, unconsciousness and fever, and right hemiplegia gradually developed. She died at the 48th day of disease from respiratory disturbance and renal failure. Cranial MRI during the acute phase of the disease, when there was no clinical sign of right hemiplegia, showed a high intensity lesion in the left parietal and occipital areas on T-2 weight image. Autopsy disclosed the findings suggesting viral encephalitis, including multiple focal necrosis, perivascular round cell infiltration, proliferation of glial cells and spongy degeneration with some intranuclear inclusion bodies, and infarction in the left hemisphere. These findings suggest that T-2 high intensity lesion on MRI reflected infarction. PMID- 1931169 TI - [Three cases of hyponatremia during administration of pimozide]. AB - Three patients with hyponatremia were found at an residential home of mental developmental delay. Because pimozide had been administered to all of them, it was suggested that pimozide might have induced compulsive water drinking resulting in hyponatremia. To my knowledge, there has been no previous report that pimozide may induce hyponatremia. As children with mental developmental delay and/or autism frequently develop epilepsy, hyponatremia should be included in the differential diagnosis of convulsive seizures. Particularly when antipsychotic drugs such as pimozide have been given, we should pay attention to polydipsia, polyuria and/or general malaise and prevent hyponatremia. PMID- 1931170 TI - [A case of Guillain-Barre syndrome treated with plasma exchange]. PMID- 1931171 TI - [PET findings after stroke in MELAS]. PMID- 1931172 TI - [Gd-DTPA enhanced MR imaging and PET in a case of Sturge-Weber syndrome]. PMID- 1931173 TI - [A study of blink reflex in myotonic dystrophy--comparison with Duchenne type muscular dystrophy]. PMID- 1931174 TI - [Streptomycin toxicity on dark cells of utricles in guinea pigs]. AB - Thirty guinea pigs were divided into three groups. The first group received intramuscular injection of streptomycin sulfate 400 mg/kg/day for one week; the second group received the same dosage for two weeks; the third group served as the control. The cochlea was dissected after treatment and the utricle observed under electron microscope. The nystagmus lasted 11.3 sec. clockwise and 12.75 sec. counter-clockwise before treatment, 10.75 sec. and 9.25 sec. after one week and 6.0 sec. and 5.5 sec. after two weeks. Histopathologic study showed the normal dark cells in the control group. In the one week group, the dark cell remained in cuboidal shape. On the luminal surface of the cell were a few microvilli and invaginations which were in the process of forming pinocytotic vesicles. In the apical cytoplasm, the coated pinocytotic vesicles, vacuoles and rough endoplasmic reticula markedly decreased. The crest of mitochondria was blur, coalescent and vacuous. The plasmalemma in the lower part of the cell reduced. In the two-weeks group, the cells became squamous with less cytoplasm and organelle. There was no pinocytotic vesicles and vacuoles in the apical cytoplasm. The luminal membrane of the cells were bulging out into the cavity. In case the membrane ruptured, the cytoplasmic organelle run into the endolymphatic space and the cell dissolved and damaged. The morphological changes indicated that streptomycin damaged the cytoplasmic granules and the plasma membrane of dark cells. These cytologic characteristics of dark cells which engaged in the fluid transport were similar to those of the secretory cells in other organs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931175 TI - [Endoscopy of porus acousticus internus]. AB - The anatomical relationships between the arterial loop and the nerve in the porus acousticus region in 50 adult specimens were studied by endoscopy via the postsigmoid approach. No trauma to the intracranial structure occurred during the study. It was found that in 68 percent of specimens a cerebellar arterial loop existed in the porus acousticus region. There were six patterns of relationship between the arterial loop and the acoustico-facial boundle. A loop between the nerves, a loop under the nerves and a loop above the nerves were the common types. In 62 percent of specimens which presented a loop in this region, the loops were in close relationship with the canal or porus. In the remaining 38 percent the loops did not show any relationship with the canal. The findings were symmetrical in only 40 percent. The separation of the vestibular and the cochlear nerves could be seen in 51.1% of the specimens. The advantages of endoscopy in this region were discussed. PMID- 1931176 TI - [Functional and morphologic changes in inner ear after experimental rupture of the round window membrane in the guinea pig]. AB - The round window membrane of the guinea pig was perforated with a sharp instrument, and electrocochleography, vestibular function and histological changes of cochlea were studied in 1, 2, 4, 7, 14 and 28 days. It was found that the compound action potential (AP) threshold and the latency increased at 95 dB (spl) sound stimulus, and vestibular function decreased slightly, but histologic appearance of Corti's organ was normal in the early stage. Latency and threshold of AP and vestibular function gradually recovered to normal 2 weeks later. If no obvious histological change took place in inner ear, hearing loss would not appear. There was no significant difference of SP changes between the experimental and control ears. PMID- 1931177 TI - [The effect of nasal sensory nerve on the enhanced nasal blood vessel permeability caused by histamine]. AB - The rats' nasal blood vessel permeability caused by histamine was significantly lower in the groups pretreated with dicaine or maxillary neurectomy than in the histamine control group. The rats' nasal blood vessel permeability also enhanced with the central side of maxillary nerve stimulated electrically. The latter effect could be blocked by pretreating with atropine. Combining with other experimental results, we suggest that the nasal sensory nerve joins the processes of the nasal blood vessel permeability enhancement caused by histamine. PMID- 1931178 TI - [An investigation of glottic movement and vocal cord evoked electromyography following unilateral cricoarytenoid joint injuries in rabbits]. AB - The unilateral cricoarytenoid joints of rabbits were bluntly injured. Observations on glottic movement and vocal cord evoked electromyography were performed. The results confirm that injury of the cricoarytenoid joint always causes disturbances in ipsilateral vocal cord movement. But the evoked electrical activities of the ipsilateral vocal cord muscles were normal not only in acute stage but also in chronic stage. The above results may provide the experimental basis for clinical differentiation of disturbances in glottic movement. PMID- 1931179 TI - [Otoneurologic manifestations of congenital abnormalities of foramen magnum region]. AB - The symptoms and signs of 38 cases of congenital abnormalities of foramen magnum region have been analysed. Twenty-six cases presented dizziness and dysequilibrium, among them 16 had spontaneous nystagmus. ENG investigation was made systematically in four cases with spontaneous and gaze nystagmus. Ocular dysmetria, decreased intensity of optokinetic nystagmus, abnormal smooth pursuit movement and failure of fixation suppression were observed. Causes of the abnormalities were reviewed. The pathophysiological bases for the changes in ENG were briefly discussed. PMID- 1931180 TI - [Transnasal endoscopic sinus surgery]. AB - The endoscopic sinus surgery is probably the most exciting topics in rhinology. Not only is the technology new, but the approach to sinus disease has changed dramatically. In this paper, we tried to present how sinus endoscopy can be applied to the treatment of sinus diseases and more radical forms of sinus surgery. Three kinds of surgical procedures were performed, they were the functional anterior ethmoidectomy, total ethmoidectomy, and total sphenoethmoidectomy for treatment of chronic ethmoid sinusitis (2 cases), polysinusitis with polyps (16 cases), and pansinusitis with polyps (5 cases). The results showed that the pus disappeared in 14 cases (60.8%), the dizziness and headache improved in 22 cases (95%), the smell improved in 14 cases (70%). There were 4 complications: nasolacrimal duct injury in one, and lamina papyracea injury in three. All of them recovered after management. PMID- 1931181 TI - [Characteristics of pediatric nasal airway resistance]. AB - The nasal airway resistance (NAR) was determined in 739 normal children and 20 patients with enlarged adenoids by means of anterior rhinomanometry. It was demonstrated that the normal value of NAR in children ranged between 1.96 and 5.26 cmH2O.s/L (1 cmH2O = 0.098 kPa) with extensive distributions and great inter personal variations. There was no significant difference of NAR between male and female in different age groups (P greater than 0.05). Adenoidal proliferation played an important role in determining the pediatric NAR. The NAR changes may be closely related to anatomical and physiological changes occurring in the nose with growing. PMID- 1931182 TI - [Computer-aided three-dimensional reconstruction of serial section of the temporal bone]. PMID- 1931183 TI - Vectors containing infrequently cleaved restriction sites for use in BAL 31 nuclease-assisted and end-label-mediated analysis of cloned DNA fragments. AB - Cloning vectors derived from plasmids pUC8 and pUC18 and phage M13mp10 were constructed so as to have multiple cloning sites (MCS) flanked by the recognition/cleavage sites for the Sfi I and Not I restriction nucleases. Cleavage of vectors containing cloned DNA fragments with either of the infrequently cleaving Sfi I or Not I endonucleases will usually yield linear DNAs cleaved only at the corresponding site in the MCS, so that the cloned insert can be degraded unidirectionally by the duplex exonuclease activity of the BAL 31 nucleases until an amount equal to the length of the vector has been degraded. The ends of the above constructs resulting from cleavage with Not I or Sfi I can readily be labeled, with labeling at only the terminus of the cloned DNA available for the Sfi I site. The BAL 31 nuclease-mediated procedures enhance a previous technique for mapping of restriction enzyme fragments, allow for localization of sequences in cloned segments for which a probe is available, and improve a method for sequencing cloned inserts through the production of sets of nested unidirectional deletions from either end of the parent cloned fragment. The advantages of end-label-mediated restriction site mapping using the above vectors over existing such procedures are also demonstrated. PMID- 1931184 TI - Agarose entrapment method for the production of SfiI linking library for Theileria parva. AB - We have developed a simple method for isolation of SfiI linking clones from a eukaryotic genomic DNA. The method involves the physical separation of the small proportion of plasmids in a plasmid genomic library that are linearized by SfiI digestion, from the bulk of molecules that remain circular, by ordinary electrophoresis through high-percentage gels of SeaPlaque agarose. Following the isolation of linearized molecules, their recircularization, and introduction into Escherichia coli, 55% of recovered plasmids contained inserts of the expected size, and 73% of these had SfiI sites. This represented a 25-fold enrichment of linking clones expected to be present at a frequency of 1/60 in the original library of 4- 6-kb fragments of genomic DNA of the protozoan parasite Theileria parva. This approach is rapid and obviates the need for introduction of a selectable marker. It is uniquely appropriate for linking clones spanning SfiI sites as this enzyme leaves degenerate 3' overhanging ends that preclude the direct ligation into vector sites required by most alternative strategies, but that favor the recircularization reactions used here. PMID- 1931185 TI - [Knowledge of acceptance and use of preventive measures in Germany]. AB - Important aspects of hygienic behaviour and patient compliance were investigated in a written survey of 500 adults. The results indicate a clear discrepancy between behaviour considered necessary by dentists and what people actually do, with reference both to thorough and methodical dental hygiene at home and knowledge of appropriate prophylactic measures. It was also seen that adults were only minimally willing to accept suggestions for improvement in their behaviour in these respects and that they were insufficiently motivated to change behaviour and habits. PMID- 1931186 TI - [Social psychological barriers to compliance in group and individual prophylaxis]. AB - In a long-term study of 700 school children attitudes and behaviour related to dental hygiene were registered and collated with findings on caries and oral hygiene. The data indicating developments in the 12 - 14 year old group showed that youths are well informed about the condition of their teeth, but are increasingly unwilling to accept treatment and advice offered by dentists. Potential barriers to compliance with prophylactic and therapeutic measures are a lack of success in school studies, insufficient accentuation of independence in the educational and child-raising process and a lack of communication between dentist and youths. PMID- 1931187 TI - [Preventive measurement in Gottingen kindergartens from 1975-1990]. AB - 379 children, age 3 to 6, were examined for caries prevalence in kindergartens in Gottingen. 64% of subjects had healthy natural dentitions, the df-s value was 2.3. In 1990 the mean df-s value for 4-5 year old children was 10% lower than 1985 and 45% lower than 1983. Oral health had improved differently in the various institutions. The mean df-s was between 0.6 and 4.7. PMID- 1931188 TI - [Oral health in children after dental care under anesthesia]. AB - Carious morbidity, oral hygiene, periodontal health, use of fluoride and therapeutic compliance were investigated in a clinical study of 41 children who had previously required insufflation anaesthesia for dental therapy. All of the children underwent postoperative treatment willingly; anaesthesia was not necessary in any of the cases. Half of the children still had a raised risk of caries; gingivitis was present in all of the children as a result of insufficient oral hygiene. For these reasons, all children that have undergone dental therapy under anaesthesia must subsequently be integrated in a programme of selective intensive prophylaxis. PMID- 1931189 TI - [Position of health education knowledge concerning pregnancy]. AB - In order to determine the level of oral hygiene education during pregnancy, 700 questionnaires from 39 hospitals were evaluated. Of the tested persons, 51% had failed to have any dental examination during their pregnancy, although approximately 65% suffered from bleeding, swelling and inflammation of the gingiva. In total 71% received no information regarding oral hygiene during pregnancy. Oral hygiene education during pregnancy either is not provided or at best inadequately available. PMID- 1931190 TI - [Efficacy of therapeutic and preventive measures with the help of bite wing radiographs]. AB - The effectiveness of caries diagnosis as seen in bite-wing pictures in the lateral dental segments was evaluated with reference to therapeutic and preventive control. Bite-wing x-rays of 328 patients aged 15-18 were included in the evaluation. The approximal segments from the ist premolars to the 2nd molars were taken into consideration. Further treatment was found to be necessary in 110 patients on the basis of the diagnoses exposed filling edge/split edge (45%), caries in dentine not adjacent to pulp (30%), secondary caries (15%) and caries in dentine adjacent to pulp (10%). Following an initial diagnosis of enamel lesions, preventive measures were necessary in 180 patients. The results document the importance of radiological checks of the permanent teeth in the approximal segments in youths. Bite-wing x-rays are also an effective means of monitoring the effectiveness of preventive measures. PMID- 1931191 TI - [Dental prevention in 3-year olds--example for preschool children]. PMID- 1931192 TI - [Effectiveness of actual information material in dental health education. Results of questioning lower Saxony orientation students]. AB - The effectiveness of dental health educational measures in the Federal Republic of Germany is often termed insufficient by specialists. In order to test this statement, a written survey was done with 903 children aged 10-14. Selected results: Most of the school children are of the opinion that what they know is derived from personal communication. Dentists, they say, have been their most important sources of information. Most of the children consider themselves to be sufficiently well-informed, a subjective judgement that cannot, however, be objectively verified by analysis of the answers dealing with concrete knowledge. PMID- 1931193 TI - [Caries protective effect of a NaF containing toothpaste with and without calcium carbonate polishing agent]. AB - A caries preventive effect depending on the free fluoride concentration was registrated on rats using dentifrices with NaF or MFP (alone or in combination) despite the presence of CaCO3 as abrasive material because the composition of these dentifrices was changed. The free fluoride concentration of dentifrices had induced the accumulation of fluoride into enamel. The ionized fluoride content of NaF-dentifrices was unchanged for 3 years. MFP was hydrolized and had continuously released fluoride ions. The caries preventive effect which was increased by HCO3- was reproducible in correspondence with the fluoride concentration after the storage for two years. PMID- 1931194 TI - [Need for dental prophylaxis in grown women: an investigation in maternal rest centers. 1. Information knowledge and or oral hygiene status]. AB - 111 women out of 316 women relaxing in three rest homes volunteered to participate in this study and answered a questionnaire concerning following subjects: daily oral hygiene, knowledge in hygiene procedures, frequency of dental treatment and interest in dental prophylaxis. Oral hygiene behaviour and knowledge were not sufficient. Only half of them knew dental floss and fluorides. Interdental care was practised by 20 women and only 10 used fluorides, they had without exception a secondary education. Most of the participants were educated in dental health care mainly by their parents. 36 women went to see the dentist only in case of necessity. 15 women were very afraid of dental treatment. 60% out of 111 women participated in a lecture on preventive dentistry and prophylaxis. PMID- 1931195 TI - [Oral hygiene in Italy]. AB - In Italy (58 million inhabitants) over the last 15 years a decrease in caries incidence could be observed: Children (6-10 years old) 1970: 84.5%, DMF-T 4.77; 1980-85: 72%, DMF-T 3.64). Per capita sugar consumption went down from 32.0 kg in 1974 to 28.2 kg in 1983. 30.770 dentists are in practice--incl. medical doctors, who are allowed to practise dentistry--, 8600 of them are members of the Italian Dental Association AMDI. AMDI together with Mentadent Gibbs organised the "Month of Mouth Prevention" in 1988, 4,400 dentists with 305,552 patients joined the programme. Thanks to this programme many data about oral hygiene in Italy have emerged: frequency of brushing, kind and choice of toothbrush, use of toothbrushes (38.5 mio sold in 1988) etc. In Italy water fluoridation ist not practised, in some areas NaF pills have been used. PMID- 1931196 TI - [Swiss organization of preventive dentistry]. AB - As a result of 25--30 years of caries research practiced in Switzerland, a level for an effective caries prevention has been reached. The results are conclusive and show that at present the caries rate has been considerably reduced. An adequate and regular application of fluoride is the basis for an effective caries prevention. Other important measures are an optimal oral hygiene and a proper nutritional diet. In Switzerland, we are coming very near to the two aims set by WHO for the year 2000 in respect of healthy teeth, namely: a) half of the 5 years olds should be caries-free, b) 12 year olds should have no more than 3 carious teeth. In many Swiss communities, these two aims have already been achieved. Group prevention begins in kindergarten (ca. 4 year olds) and continues up to the fourth year of ground school education. On entering the middle school level (ca. 11 years olds), the patients leaves the group-prevention and receives individual prevention instruction. Also the substance matter changes from caries-prevention to gingivitis-prevention. It seems that with group-prevention, no noticeable improvement has been made against gingivitis. Carrying out the program are private local dentists with contract arrangements, or the canton's school dental clinic. The dentist delegates the prevention program to specially trained personnel. Public funds finance the prevention measures in its entirety. In the last few years we have discovered a small group of patients showing a higher caries-susceptibility despite the general improvement of oral hygiene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931197 TI - [Fissure sealants as primary preventive measures. Four-year evaluation in Stara Pazova]. AB - Worldwide studies have shown that fissure caries prophylaxis is very difficult using conventional preventive methods. The scientific council of the prophylaxis programme for the protection of mouth and teeth in Vojvodina has begun sealing fissures in Stara Pazova and Novi Sad. The molars of all 6-year-old children were sealed completely. A 77.8% reduction in fissure caries was found at the end of the four-year study. Losses of sealing material came to 16% after four years. Cost-effectiveness analysis: The sealings are three times cheaper than an amalgam filling. Application time: 8-9 minutes. PMID- 1931198 TI - [Denta-Solar--comparison with a traditional toothbrush]. AB - This paper reports on the clinical efficacy of a toothbrush (Denta-Solar) with an integrated TiO2 semiconductor element as compared to a conventional toothbrush. A significant reduction in the papilla bleeding index and the plaque indices was recorded in subjects using the Denta-Solar brush; the tartar situation near the gingivae was seen to deteriorate in those using conventional toothbrushes. This supports the assumption that the plaque reduction is due to the special construction features of the Denta-Solar. PMID- 1931199 TI - Asthma care in general practice--time for revolution? PMID- 1931200 TI - Audit of the effect of a nurse run asthma clinic on workload and patient morbidity in a general practice. AB - The aim of this study was to assess the effect of a nurse run asthma clinic on practice workload and the morbidity of patients in a four partner general practice. One hundred and fifteen asthmatic patients were studied and comparisons were made between the 12 months prior to the introduction of the clinic and the first 12 months after the clinic started. Morbidity was measured in terms of: the number of courses of oral steroids, the number of emergency salbutamol nebulizations, and the number of days lost from work or school. The number of consultations with the general practitioners were recorded. The repeat prescribing register was also monitored throughout the study to examine the effect of the clinic on prescribing in the practice. Consultations with general practitioners fell from a total of 818 to 414 during the study period (P less than 0.001). This was offset by 496 consultations with the nurse in the first 12 months of the clinic. As a result of attending the nurse clinic significant reductions (P less than 0.01) were found in the patients' requirements for courses of oral steroids, acute nebulizations and days lost from work or school. The results for the 46 children were similar to those for the 69 adults, confirming that the asthma clinic was effective for all ages. The clinic coincided with an increase in the number of patients receiving regular bronchodilator therapy and prophylactic medication. Eighty per cent of patients had their medication modified as a result of attending the clinic. The cost of prescribing remained remarkably stable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931201 TI - Measuring success in asthma care: a repeat audit. AB - An asthma audit was first performed in 1984 in a two-doctor semi-rural training practice in Shroshire with 4400 patients. This paper reports on a repeat of the audit in 1987 in the same practice, following a programme of minimal intervention. Interviews were conducted with 192 asthmatics, 96% of those known to the practice on a manual register. Between the 1984 and 1987 audits there was a significant increase in ownership of peak flow meters and their use for monitoring progress and an improvement in inhaler technique. There was a general improvement in patients' knowledge about asthma. Inadequate control was shown in 22% of the sample in 1987, but half of these patients were known to be non compliant. There were significant improvements in scores for asthma disability in night-time symptoms in children (P less than 0.05) and in daytime symptoms in adults (P less than 0.001) between 1984 and 1987. It is concluded that improved levels of asthma care have been achieved in a small practice using checklists, booklets and repeated audit, but without structured follow up or an asthma clinic. PMID- 1931202 TI - Attitudes to carrier screening for cystic fibrosis: a survey of health care professionals, relatives of sufferers and other members of the public. AB - The gene which is mutated in cystic fibrosis has now been identified, thus permitting the detection of carriers in the general population. This paper reports pilot surveys in the North West Thames region of the health service to assess knowledge of people about cystic fibrosis and their attitudes towards screening. Three groups were surveyed: a group of relatives of those with cystic fibrosis (n = 268), a sample of the community (school pupils and family planning clinic attenders, n = 363), and a group of health care professionals (general practitioners and family planning clinic staff, n = 227). The relatives of cystic fibrosis sufferers were unanimously in favour of the introduction of cystic fibrosis screening, and the results indicate that there is likely to be support from the relevant health professionals: approximately 75% of respondents in the group of health care professionals believe the introduction of screening would be worthwhile. Data from the community sample suggest that, although knowledge of cystic fibrosis within the general community is low (less than 50% of respondents realized that cystic fibrosis affects the lungs and that no cure is available), there is likely to be considerable demand for carrier testing from the general public. Approximately 75% of the community sample indicated that they would like to be tested. There was no clear consensus, either from the professionals or the public, as to the best time to offer screening. PMID- 1931203 TI - Factors associated with regular episodes of dysuria among women in one rural general practice. AB - The aim of this study was to ascertain the factors associated with frequency dysuria (urethral) syndrome in a population of women. The study included all women aged 25 years and over on 1 May 1987 who had been registered with one rural, dispensing practice over the study period, 1 May 1985 to 1 May 1989. A self-administered questionnaire was sent to the women on 1 May 1987 and a second, similar, questionnaire was sent two years later. A total of 721 women responded to the two questionnaires (response rate 97%). Regular symptoms of frequency and dysuria were reported by 8% of women in 1987 and 14% in 1989. Four percent of women reported symptoms throughout the four year study period. Symptoms were found to be least common in the 55-74 years age group. Although none of the women who were sexually inactive reported regular symptoms no association was reported between recent sexual intercourse and symptoms. Neither was an association demonstrated between type of contraception used and symptoms. However, it was found that premenopausal women reported significantly more symptoms than postmenopausal women. The number of women involved in this study was too small to allow the importance of change of sexual partner to be determined. Significantly more of the women who reported regular symptoms had been treated for urinary tract infection than of those who did not report regular symptoms. Although a history of regular frequency and dysuria points to a diagnosis of urethral syndrome, general practitioners must assess each case in order to exclude urinary tract infection. PMID- 1931204 TI - How well are parent held records kept and completed? AB - During 1986 and 1987 parents in part of the Oxfordshire district health authority were given their child's health and development records while in the other part of the health district the records remained with the clinic. Between August 1988 and February 1989 an audit was made of a sample of parents attending child health clinics in the two areas: the study examined 284 parents who had parent held records and 168 who did not; how many records were available and if not, why not; how well and by whom records were completed and parents' views on who they felt should keep the record. Interviews revealed that parents with a parent held record liked the scheme and were confident about remembering to take the record to the clinic. Those without experience were less confident and more concerned about losing the record. At the time of the audit 7% of parent held records had been lost or forgotten, but 5% of clinic held records were not available for inspection. Overall, parent held records were more likely to have comments contributed by parents and to be more thoroughly completed by professionals. The results suggest that parent held records are not only workable but desirable. PMID- 1931205 TI - Primary care psychiatry: the case for action. AB - Since the introduction of the National Health Service a number of epidemiological enquiries have established the importance of mental disorders in the field of primary care. Examples are provided from the work of the General Practice Research Unit at the Institute of Psychiatry in London. The results furnish a rational basis for collaborative action between research workers, general practitioners and policy makers. PMID- 1931206 TI - The care of children with asthma in general practice: signs of progress. PMID- 1931207 TI - Management of urinary tract infection. PMID- 1931208 TI - Knowledge of common inherited disorders among family planning clinic attenders. PMID- 1931209 TI - Consultation length debate. PMID- 1931210 TI - Crying babies. PMID- 1931211 TI - Management of myocardial infarction. PMID- 1931213 TI - Diplomatosis. PMID- 1931212 TI - Which antidepressant? PMID- 1931214 TI - Complaints and patient expectations. PMID- 1931215 TI - Standardized patients in general practice. PMID- 1931216 TI - Nutrition of Australian aboriginal infants and children. PMID- 1931217 TI - The health effects of day care. PMID- 1931218 TI - Ioxaglate in paediatric angiocardiography. AB - It is generally agreed that low osmolar contrast media are better tolerated than conventional media. This study examined both tolerance and image quality of ioxaglate in a group of paediatric patients undergoing angiocardiography for congenital heart disease. A consecutive series of 50 patients (mean age 5.47 years; range 4 days-14 years) were examined. The mean dose of ioxaglate administered per patient was 2.93 mL/kg. In general, ioxaglate was well tolerated. Three patients became febrile and another developed eosinophilia. Serum creatinine rose by a mean of 10 mumol/L. Significant renal dysfunction occurred in 12 patients with an increase in creatinine of 20-30 mumol/L. In no patient, however, were these effects a significant clinical problem. Diagnostic image quality was generally considered to be good with both cine-angiography and digital subtraction angiographic techniques. PMID- 1931219 TI - Retinal haemorrhage in accidental head trauma in childhood. AB - Twenty-five children (age range 1.2-14.5 years) who sustained accidental head injury requiring admission to hospital were prospectively examined for evidence of retinal haemorrhage. In no case were retinal haemorrhages detected. It is suggested that accidental head injury seldom results in retinal haemorrhage and that the finding of retinal haemorrhage in a child with a head injury should prompt suspicion of abuse. PMID- 1931220 TI - The relationship between children's treatment-related behaviour problems, age and clinical status in cystic fibrosis. AB - This study examined the relationship between parents' and physicians' reports of treatment-related behaviour and adjustment problems of children with cystic fibrosis (CF), and children's clinical status as assessed by measures of pulmonary functioning and global ratings of clinical status. Parents completed a Cystic Fibrosis Problem Checklist which measures the extent to which children experience behaviour and adjustment difficulties with different aspects of treatment, including chest physiotherapy, medication taking and diet. A high proportion of parents in each age group reported at least some treatment-related behaviour difficulties, with significantly more problems being reported with younger children. There was no significant relationship, however, between the child's age, sex and clinicians' ratings of compliance. A stepwise multiple regression showed that the only variables which significantly predicted clinicians' ratings of the severity of the child's disease were forced expired volume and height. Clinicians' ratings of compliance explained a small amount of extra variance (2.4%). It was found that parental reports of treatment-related behaviour problems were not related to clinical status. The implications of the findings for clinical practice are discussed. PMID- 1931221 TI - Malnutrition in children with chronic liver disease accepted for liver transplantation: clinical profile and effect on outcome. AB - The nutritional profiles of 37 children (aged 0.5-14.0 years) with chronic liver disease at the time of acceptance for orthotopic liver transplantation (OLTP) have been evaluated using clinical, biochemical and body composition methods. Nutritional progress while waiting for a donor has been related to outcome, whether transplanted or not. At the time of acceptance, most children were underweight (mean standard deviation (s.d.) weight = -1.4 +/- 0.2) and stunted (mean s.d. height = -2.2 +/- 0.4), had low serum albumin (27/35) and had reduced body fat and depleted body cell mass (measured by total body potassium--mean % expected for age = 58 +/- 5%, n = 15). Mean ad libitum nutrient intake was 63 +/- 5% of recommended daily intake (RDI). Those who died while waiting (n = 8) had significantly lower mean initial s.d. weight compared with those transplanted. The overall actuarial 1 year survival of those who were transplanted (mean waiting time = 75 days) was 81% but those who were initially well nourished (s.d. weight greater than -1.0) had an actuarial 1 year survival of 100%. There were no significant differences in actuarial survival in relationship to age, type of transplant (whole liver or segmental), liver biochemistry or the presence or absence of ascites. Of the total group accepted for OLTP, whether transplanted or not, the overall 1 year survival for those who were relatively well nourished was 88% and for those undernourished (initial s.d. weight less than -1.0) was 38% (P less than 0.003). Declining nutritional status during the waiting period also adversely affected outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931222 TI - Inguinal hernia in very low birthweight children: a continuing risk to age 8 years. AB - The prevalence of inguinal hernia repair up to 8 years of age was determined in 205 inborn children of birthweight less than 1500 g who had survived to the age of 8 years; 37 (18.0%) of the children required surgery for inguinal hernia, significantly more frequently for boys than girls (32.0% and 3.9% respectively). The cumulative percentage of inguinal hernia operations in boys was 8.7% during primary hospitalization, 20.4% by 2 years, 30.1% by 5 years and 32.0% by 8 years; 36.4% (12 of 33) hernias in boys occurred beyond 2 years of age. The risk of hernia in boys was only marginally higher in those who required assisted ventilation and in those of birthweight less than 1000 g. Very low birthweight infants, particularly boys, are at risk of developing an inguinal hernia not only in infancy but also to at least 8 years of age. PMID- 1931223 TI - Birth asphyxia associated oliguria: relationship to outcome at 1 year. AB - The relationship between the degree of oliguria following severe birth asphyxia and outcome at 12 months was examined in 31 infants. All 31 infants developed encephalopathy following severe birth asphyxia and 25 had oliguria for 24 h or more following delivery. Eighteen had persistent oliguria (i.e. greater than 48 h) and the remaining seven had transient oliguria (between 24 and 48 h). Poor outcome (death or neurological abnormality at 12 months) was significantly associated with the degree of oliguria. Encephalopathy, however, was found to be more closely correlated with poor outcome rather than duration of oliguria and a stepwise regression model confirmed that encephalopathy was the more powerful predictor of poor outcome. In those situations where an infant's degree of encephalopathy can not be assessed accurately (e.g. muscle relaxant use) the duration of oliguria may prove a useful prognostic indicator. PMID- 1931224 TI - Benign intracranial hypertension in childhood: a review of 23 patients. AB - Twenty-three patients with benign intracranial hypertension (BIH) were seen at the Royal Alexandra Hospital for Children, Sydney over an 18 year period to 1988. Age at presentation ranged from 6 months to 13 years and 5 months. The female to male ratio was 2.3:1. The aetiological factors (sometimes multiple) included: chronic middle ear infection, 30%; dural sinus thrombosis, 22%; head injury, 13%; Vitamin A overdosage, 4%; tetracycline exposure, 4%; and no apparent cause, 43%. Headache was the most common presenting symptom occurring in 91% of patients, followed by vomiting in 65% and blurred or double vision in 57%. Papilloedema occurred in 96% of patients, abducens palsy was noted in 48% and visual impairment in 45%. All patients improved clinically after treatment, one with lumbar puncture only. Of 17 patients treated with steroids, 10 patients recovered and seven patients went on to lumboperitoneal shunt. Two patients recovered with steroid and diuretic treatment. Of two patients initially treated with diuretics only, one recovered and one subsequently required a shunt. Only one patient was initially treated with a lumboperitoneal shunt. Three of the shunted patients had shunt block requiring revision. None had permanent visual loss or other significant sequelae. The visual prognosis of BIH in childhood is good. In view of the relatively high complication rate of steroids and shunting, a controlled comparison of steroid vs acetazolamide/diuretic therapy should be undertaken. PMID- 1931225 TI - Impact of influenza on morbidity in children with cystic fibrosis. AB - Recommendations concerning annual influenza vaccination in children suffering from cystic fibrosis (CF) are not uniform. Previous studies have shown that influenza causes a small proportion of episodes of acute respiratory deterioration in CF patients. During the 1989 Australian winter, we studied the association between serologically proven influenza infection and acute respiratory morbidity in 20 children with CF. Six children were shown to have influenza infection, four with type A and two with type B. Four of five children requiring hospital admission were shown to have influenza, but only 2 of 15 did not need admission (P less than or equal to 0.025). As well, influenza was diagnosed in 6 of 12 children who suffered acute respiratory illness leading to school absenteeism (including hospitalization), but diagnosed in no children without this degree of illness (P less than or equal to 0.025). Influenza significantly increases the incidence of hospitalization and of less serious respiratory illness in children with CF, a finding which suggests that influenza vaccine efficacy studies are necessary in this group. PMID- 1931226 TI - Plant cardiac glycosides and digoxin Fab antibody. AB - The potential application of the Digoxin Fab antibody (Wellcome Digibind) in the clinical management of plant poisoning was investigated. The cardiac glycoside contents of various Australian plants were studied using immunoassay techniques. The cross-reactions of the Fab antibody and two digoxin assay antibodies against extracts of these plants were also studied. Results obtained indicated that the Digibind antibody cross-reacted with a wide range of glycosides contained in Australian plants and therefore could be of use in the treatment of life threatening plant poisoning. PMID- 1931227 TI - Sound policy, not AIDS hysteria. PMID- 1931228 TI - Hypothetical assignment of intrachain disulfide bonds for HIV-2 and SIV envelope glycoproteins. PMID- 1931229 TI - Posttranslational modifications within the HIV-1 envelope glycoprotein which restrict virus assembly and CD4-dependent infection. AB - Alterations in two highly conserved N-linked glycosylation sites within the gp120 envelope glycoprotein of human immunodeficiency virus type I (HIV-1) implicated in the phenotype of a noncytopathic HIV-1 variant were introduced independently and in combination into a cytopathic, infectious HIV-1 clone by site-specific mutagenesis. Neither mutation affected the synthesis of HIV-1 envelope glycoproteins. However, one of the mutations restricted the ability of HIV-1 envelope to localize on the cell membrane and thus markedly impaired virus assembly. The HIV-1 assembly defect could be overcome in trans if site-specific mutants were packaged in HeLa cells constitutively producing wild-type HIV-1 envelope glycoprotein. In addition to inefficient virus assembly, this mutation impaired the ability of the virus to infect CD4+ T cells, but did not affect CD4 independent infection of muscle cells. These results suggest additional functions of posttranslational modification in virus replication (i.e., envelope glycoprotein transport). Given that such modifications can restrict CD4-mediated uptake without affecting CD4-independent uptake, variations in posttranslational env processing between different HIV-1 genotypes may affect virus tropism in vivo. PMID- 1931230 TI - Synthetic peptides allow discrimination of structural features of CD4(81-92) important for HIV-1 infection versus HIV-1-induced syncytium formation. AB - Benzylated peptides with a primary amino acid sequence corresponding to either human CD4(81-92) (#18), or chimpanzee CD4(81-92) (#18C), were equipotent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection of CD4+ cells and high-affinity binding of 125I-gp120 to CD4+ cells. The chimpanzee-based CD4(81-92) peptide, however, which differs from the human peptide by a single amino acid substitution (E for G) at position 87, was considerably less potent than the human CD4(81-92)-based peptide congener to inhibit HIV-1-induced cell cell fusion. These data suggest that a portion of the CD4 molecule contained within the sequence CD4(81-92) is involved in binding gp120 during both HIV-1 infection and HIV-1-induced syncytium formation in human cells, but that the presence of a glutamic acid at position 87 in this sequence is more critical for the CD4/gp120 interaction leading to syncytium formation than for the CD4/gp120 interaction leading to primary infection of CD4-positive cells. The region CD4(81 92) may critically contribute to CD4-mediated HIV-1 pathogenesis in humans, and its alteration might explain the lack of pathogenic sequelae of HIV-1 infection in chimpanzees. PMID- 1931231 TI - Construction of CD4-based chimeric molecules by chemical cross-linking. AB - A simple method by which a soluble form of human CD4 (sT4) is chemically coupled to various carriers using a bifunctional reagent is described. The cross-linking of sT4 and carriers is accomplished with sulfosuccinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC) which creates a covalent bond between free NH2 and SH groups. If necessary, SH groups are introduced at the surface of the carriers using 2-iminothiolane. The method is simple, fast and efficient, and creates a thioether (S--C) bond which cannot be cleaved and thus gives stability to the construct in vivo. As an example of the applicability of this approach, sT4 was coupled to human serum albumin, a monoclonal antibody, and red blood cells. We show that for all of the sT4 conjugates, the cross-linking procedure conserved the sT4 reactivity for the gp120 and anti-CD4 monoclonal antibodies. Additionally, the sT4-Ig conjugate retained the binding specificity of the Ig portion and the cross-linking of sT4 to RBC proved to be very efficient and homogeneous. Altogether, this procedure allows the construction of chimeric molecules that cannot be obtained by genetic engineering and this may present many useful applications in the preparation of CD4-based anti-HIV drugs which could be rapidly constructed and screened. PMID- 1931232 TI - N-acetylcysteine inhibits latent HIV expression in chronically infected cells. AB - The progression of the human immunodeficiency virus (HIV) infection from its early latent (asymptomatic) stage to active, late-stage acquired immunodeficiency syndrome (AIDS) apparently begins with the production of inflammatory cytokines that stimulate the expression and replication of the latent virus. We have shown that N-acetylcysteine, a cysteine precursor that is converted intracellularly into glutathione, blocks cytokine-stimulated HIV replication in an acutely infected T-cell line and in acutely infected peripheral blood mononuclear cells from normal individuals. In this report, we show that N-acetylcysteine also inhibits stimulated HIV expression in chronically infected monocyte and T-cell lines which are used as models for latent infection in AIDS. Furthermore, we show that N-acetylcysteine blocks viral production in monocyte cell lines more effectively than it blocks viral production in T cells. Since monocytes are a major reservoir for HIV in infected individuals, these results suggest that N acetylcysteine may slow the change from latency to the later stages of AIDS in HIV-infected individuals. PMID- 1931233 TI - Immune response to HIV p24 core protein during the early phases of human immunodeficiency virus infection. AB - The immune response to the p24 core antigen of human immunodeficiency virus type 1 (HIV-1) was studied in serial samples collected prospectively from 52 homosexual males in two separate cohorts from Amsterdam and San Francisco. p24 antibody levels were quantified with an antigen sandwich immunoassay using p24 recombinant antigen as capture and probe. Titers and slopes of dilution curves reflecting antibody affinity were analyzed. Only 45 of 52 men developed a measurable primary immune response to p24. In 17 (33%) patients there was a low response with maximum antibody titer below 66, shallow (low affinity) dilution curve, and 10 of the 17 became HIV antigen positive over a 2 year period. In 24 (46%) of the 52 patients titers ranged from 100-4000, steeper dilution curves were noted, and none became HIV antigen positive. Four (8%) men developed a strong immune response with high titers (greater than 12,000) and high affinity type dilution curve. Over time, after the peak immune response, antibody titer declined in some individuals related in part to the formation of immune complexes between HIV-1 p24 antigen and antibody which were dissociable. In vitro, the addition of increasing amounts of purified p24 antigen corresponded to decreasing antibody titer and a shallower dilution curve suggesting a preferential consumption of high affinity antibodies for complex formation. The magnitude of immune response to HIV-1 p24 antigen varies widely in infected homosexual men. Both the intrinsic ability to mount an immune response and immune complex formation contribute to the measurable antibody level. PMID- 1931234 TI - Induction of HIV-specific CTL and antibody responses in mice using retroviral vector-transduced cells. AB - Recombinant retroviral vectors can efficiently transduce and express foreign genes in mammalian cells. We have examined the utility of retroviral vector mediated gene transfer to deliver genes which encode human immunodeficiency virus type I (HIV) antigens capable of stimulating specific immune responses. Murine fibroblast cell lines were transduced with a nonreplicating murine retroviral vector carrying the gene encoding the HIV-IIIB envelope protein and were shown to express the gp160/120 protein. Mice immunized with syngeneic vector-transduced cells developed CD8+, class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) specific for targets expressing the HIV envelope protein. The CTL also exhibited lytic activity on target cells coated with synthetic peptides derived from the gp120 V3 hypervariable region of both the HIV IIIB and HIV(MN) isolates. Following adoptive transfer in a murine tumor model, these CTL were shown to be effective in vivo by their ability to eliminate established tumor cells expressing the HIV protein. Vector-transduced syngeneic cells were also capable of eliciting HIV envelope-specific antibody responses in immunized mice. Sera obtained from these mice were found to bind to the HIV-IIIB gp160 protein as well as a peptide-defined neutralizing antibody epitope contained within the V3 domain of gp120. These sera exhibited virus-neutralizing activity in that they markedly reduced the ability of HIV to infect and form syncytia of a human T-cell line. This is the first demonstration that cells transduced with a retroviral vector encoding the HIV-IIIB envelope protein are capable of inducing effective HIV-specific cellular and humoral immune responses in mice. PMID- 1931235 TI - Interleukin-6 expression in primary macrophages infected with human immunodeficiency virus-1 (HIV-1). AB - We have investigated the effects of human immunodeficiency virus type-1 (HIV-1) infection on constitutive and lipopolysaccharide (LPS)-induced expression of interleukin-6 (IL-6) in cultured blood monocyte-derived macrophages. Highly productive and cytopathic infection of macrophages was established with the macrophage-tropic HIV-1 BaL strain. On Days 14-28 post infection, infected and mock-infected cells were activated with LPS or control medium for 6-24 hours before harvesting culture supernatants and cellular RNA. IL-6 bioactivity in culture supernatants was measured with the IL-6-dependent B9 cell line. IL-6 mRNA levels were quantitated by Northern blot analysis with scanning densitometry. In the absence of LPS activation, IL-6 activity was near or below the limit of detection in supernatants from both infected and uninfected cultures. Similarly, without LPS stimulation, IL-6 mRNA was not detectable in either infected or uninfected macrophages. After activation with LPS, marked increases in IL-6 mRNA levels and supernatant bioactivity were evident in both infected and uninfected cultures, but the response to LPS was consistently greater in infected macrophages. LPS-induced IL-6 mRNA levels and supernatant bioactivity were 7.4- and 4.4-fold higher, respectively, in infected compared with uninfected macrophages (n = 5, p less than .05). These studies demonstrate that highly productive HIV-1 infection does not increase constitutive IL-6 expression in macrophages, but does prime macrophages for an augmented IL-6 response to LPS. These findings may help define the mechanisms responsible for increased IL-6 production in patients with HIV-1 infection. PMID- 1931236 TI - Relative activities of HIV-1-IIIB and HIV-1BaL LTR and tat in primary monocytes and lymphocytes. AB - The mechanisms determining the ability of some but not other strains of human immunodeficiency virus type 1 (HIV-1) to grow in peripheral blood monocyte macrophages are presently unclear. The tat gene of HIV-1-IIIB which replicates poorly in human macrophages, and the tat gene of HIV-1-BaL, which replicates to high titers in the same cells in transient expression systems with their respective long terminal repeats (LTR) driving a reporter chloramphenicol acetyl transferase (CAT) gene were compared. The authors hypothesized that the tat gene and LTR of BaL might help account for its efficient growth in primary monocyte macrophages by virtue of a high activity in these cells relative to that of the IIIB tat and LTR. Primary peripheral blood lymphocytes and monocytes were cotransfected with either the HIV-1BaL or HIV-1-IIIB LTR fused to the CAT gene and their respective tat genes. The IIIB tat and LTR were at least as active in primary lymphocytes as the BaL combination, and both tat-LTR pairs were more active in primary lymphocytes than monocytes. The same relative activities were also observed in primary monocytes after in vitro maturation to macrophages prior to transfection. These data strongly suggest that neither the tat gene nor the LTR of HIV-1-IIIB and HIV-1BaL can account for the great ability of the latter or the inability of the former to grow in monocyte-macrophages. PMID- 1931237 TI - Nef proteins of the human immunodeficiency viruses (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV) are structurally similar to leucine zipper transcriptional activation factors. AB - Analysis of the predicted amino acid sequences of the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and of the related simian immunodeficiency virus (SIV) nef gene products (Nef) reveals the presence of a conserved leucine zipper-like repeat with the characteristic 4,3 arrangement of mainly hydrophobic amino acids in the middle (core) region of the proteins, but lacking the basic (DNA binding) domain characteristic of DNA-binding leucine zipper (bZIP) proteins. Also, at the C-terminus of the Nef proteins is a highly acidic sequence (net charge of -5 to -8) stretched over about 40 amino acids, and contains two predicted alpha-helices separated by a beta-turn linker sequence with sequence homology to known activation domains of acidic transcriptional activation factors. Moreover, within this acidic region of transcriptional activators and the homologous sequence within the second Nef alpha-helix, is a potential transcriptional activation consensus sequence (TACS) bounded by a pair of acidic amino acids (aspartic or glutamic acids) at the N-terminus and a highly invariant phenylalanine (hydrophobic), often followed by an acidic (aspartic) residue, at the C-terminus of the sequence. These findings strongly implicate Nef proteins as belonging to a class of non-DNA-binding leucine zipper acidic transcription factors, and provide a structural basis for new approaches to studying Nef function. PMID- 1931238 TI - [Gammagraphy with sucralfate labelled with technetium in esophagitis]. AB - In previous studies it has been reported that, after being labeled with technetium, sucralfate, an useful drug in peptic diseases, can be used to detect peptic lesions of the digestive tract. In this work we report our experience with this technique in the diagnosis of esophagitis. 25 studies (11 controls and 14 patients) were undertaken. Sucralfate scintigraphy was normal in the 11 control studies, and abnormal in 10 out of 14 patients. Scintigraphy was abnormal in peptic as well as caustic lesions. PMID- 1931239 TI - [Comparative multicentric study of omeprazole versus ranitidine in the treatment of duodenal ulcer]. AB - A total of 158 patients, aged 19-78 years and with endoscopically verified duodenal ulcer of at least 5 mm in maximum diameter were recruited. 79 patients were randomised to treatment with omeprazole, a proton-pump inhibitor of the parietal cell, and 79 patients were treated with ranitidine. This double blind study is the first clinical trial with omeprazole in Spain. Using "intention to treat" analysis there was no difference in healing rates at 2 weeks between the omeprazole group (70%) and the ranitidine group (59%) with p = 0.13. At four weeks, however, omeprazole healed significantly more patients (92%) than ranitidine (76%) with p = 0.005. Using per protocol analysis a similar result was obtained with no significant difference between omeprazole (71%) and ranitidine (63%) at two weeks (p = 0.3) but significantly greater healing on omeprazole at 4 weeks (97%) compared with ranitidine (83%) with p = 0.008. The influence of additional prognostic factors was assessed using a multivariate analysis. At two and four weeks, there was a significant effect of ulcer size on healing rate. At four weeks there was also a significant effect of treatment. Symptom relief was rapid in both treatments but the omeprazole group had significantly fewer days of pain and better patient's overall evaluation than ranitidine group. No serious adverse events were reported. In conclusion omeprazole healed significantly more duodenal ulcers than ranitidine and symptom relief was more rapid during omeprazole therapy. PMID- 1931240 TI - [Precancerous conditions in gastric cancer (II): relationship between atrophic gastritis-intestinal metaplasia-gastric dysplasia-gastric carcinoma]. AB - We studied a group of gastric precancerous lesions in order to analyze their mutual relationship as well as and their association with the development of gastric carcinoma of the intestinal type. This study was performed on 850 gastric biopsy specimens. Our results demonstrate the strong association of atrophic gastritis, intestinal metaplasia and gastric dysplasia (p less than 0.001) which should be considered as precursor lesions of gastric cancer. Moreover, the relations between these lesions and the intestinal type of gastric carcinoma suggest their active participation in the genesis of this type of malignancy. Our results also suggest that chronic atrophic gastritis and intestinal metaplasia evolve to the dysplasia stage before developing gastric cancer. PMID- 1931241 TI - [Colorectal carcinoma. Multifactorial analysis of prognostic factors following curative resection]. AB - Cox regression analysis was used in the study of 151 cases of surgically treated colorrectal carcinoma. A "curative" resection was performed in all of them. Clinical data from medical records, histology, biochemical determinations, and intraoperative findings were assessed. Four of the studied variables were significantly related to tumor recurrence: Dukes stage, tumor spread, histological variety and preoperative CEA level. Age, sex, tumor location, surgical technique, lymphocytes in the peripheral blood, preoperative levels of acute phase reactants and hepatic enzymes did not provide information about the final outcome of these patients. An index of prognosis was statistically obtained in order to identify a high risk of recurrence group of patients, who may benefit from adjuvant therapy. PMID- 1931242 TI - [Effect of the resection margin and the extrarectal spread on the recurrence following 2 types of surgical procedures in rectal cancer]. AB - A prospective unrandomized clinical study was conducted to determine the incidence of local recurrences after radical surgery and to ascertain whether the anterior resection could be an effective approach in cases of the tumours of the rectum, also in presence of the unsatisfied distal clearance and the extraparietal spread. For this purpose the length of the rectum below the tumor, mesorectum included, was cut in little cubes of 1 square cm and 10 microslices/cm at random were histologically examined to locate the intramural diffusion and extraparietal spread. Sixty-one patients undergoing curative surgery for rectal cancer entered the trial. Thirty-seven of them have been operated on by anterior resections (AR) and twenty-four by abdominal-perineal amputation. Thirteen local recurrences (21.3%) have been recorded during a five-year follow-up: 9 after AR and 4 after Miles operation. Nine relapses were among the cases with distal clearance less than 3 cm an eight of these have undergone anterior resections. No recurrence was seen in cases with distal clearance greater than 5 cm. Spread was found in 11 (18%) patients. Five recurrences were recorded all belonging to the group with anterior resection. No statistical difference exists between conservative surgical procedure and abdominal-perineal operation. We have been able to demonstrate only the direct relationship between relapse and Dukes C stage after curative rectal surgery. PMID- 1931243 TI - [Caroli's disease. Presentation of 8 cases studied with ERCP]. AB - Eight patients with Caroli's Disease are presented, studied by Endoscopic Retrograde Cholangiopancreatography (ERCP) from January 1976 through January 1990. In this period of time 1,525 procedures were carried out, this entity thus representing 0.52% of patients submitted to ERCP in our population. Six patients were females, being female: male ratio 3:1. Mean age was 52 years (range: 40-75). All patients presented a clinical history of recurring episodes of abdominal pain and/or crisis of cholangitis. In the ERCP carried out in these eight patients, cystic dilatation of intrahepatic left lobe bile ducts were confirmed in five patients, dilatation generalized to both lobes in two, and affecting exclusively the right lobe in one patient. PMID- 1931244 TI - [Anatomic and physiopathologic basis of surgery of the distal common bile duct]. PMID- 1931245 TI - [Reoperations after esophagomyotomy in esophageal motility disorders]. AB - Out of 96 patients with the diagnosis of primary esophageal motor disorders and treated by esophagomyotomy, a group of 9 patients is reported in whom reoperation was necessary because of persistence or worsening of the previous symptoms (8 patients) or persistent reflux esophagitis (one patient). Clinical and laboratory examinations together with the operative findings allowed classification of these patients: incomplete myotomy proximally (4 patients) or distally (one patient), fibrotic scar at the site of previous myotomy (2 patients), persistence of intact muscle fibers (one patient) and reflux esophagitis for lack of an antireflux intervention during myotomy. Treatment consisted of completing myotomy proximally or distally, resection of the fibrous tissue and an antireflux operation when indicated. Clinical results were excellent in 6 patients (66.6%), fair in 2 patients (22.2%) and bad in one case (11.1%). Fair or bad results were seen in patients with total absence of motor response to deglutition. After operation there was disappearance of vigorous contractions in the esophagus, as shown by manometry and recovery of esophageal peristalsis in another patient. We conclude that in order to improve the results of the surgical treatment of motor esophageal disorders it is essential to correctly classify the type of disorder present by means of manometry and to add a partial funduplication to ensure absence of reflux without dysphagia. PMID- 1931246 TI - [Dysphagia of vascular origin]. AB - Three adult patients presented with dysphagia due to vascular compression of the esophagus. In one case, a dysphagia aortica was diagnosed. In the remaining two cases a congenital vascular anomaly--aberrant right subclavian artery and right aortic arc, respectively--was proved by arteriography. The final diagnosis was suspected after the barium meal and confirmed by computarized tomography in each case. PMID- 1931247 TI - [Colonic tuberculosis. Endoscopic diagnosis]. AB - We present a patient with acute and severe abdominal pain, fever and mild tenderness elicited on deep palpation in the right lower quadrant. X-ray films of the chest and abdomen were normal. The ultrasonographic study, barium enema examination and colonoscopic study avoided a diagnostic laparotomy. A purified protein skin test (PPD) and the cultures on Lowestein medium were negative. The final diagnosis was ulcero-hipertrophic tuberculosis of the ascending colon, and was confirmed by the finding of positive acid fast facilli and granulomas with Langerhans cells in the colonic biopsy material. The colonic lesions disapplared at the end of the antituberculous treatment. PMID- 1931248 TI - [Acute pancreatitis and afferent loop syndrome]. AB - A new case of afferent loop obstruction presenting as acute pancreatitis is described. It is an uncommon manifestation of the afferent loop syndrome: less than 20 cases found in the literature. The diagnosis of afferent loop obstruction should be suspected in any patient with acute pancreatitis and a previous Billroth II gastrectomy. Duodenopancreatic reflux seems to play an important role in the pathogenesis of acute pancreatitis in this situation. The "closed duodenal loop" experimental model of acute pancreatitis simulates quite closely this clinical situation. The physiopathological principles, diagnosis and treatment of this syndrome is reviewed. PMID- 1931249 TI - [Eosinophilic gastroenteritis with esophageal and rectal involvement]. PMID- 1931250 TI - [Multiple visceral aneurysms (left hepatic and splenic arteries) successfully treated with surgery]. PMID- 1931251 TI - [Leiomyosarcoma of the rectum. Report of a case staged using endorectal echography]. PMID- 1931252 TI - [Anaphylactic shock as the first manifestation of hydatidosis]. PMID- 1931253 TI - [Parkinson's disease; etiology and animal model]. PMID- 1931254 TI - [Aging and Parkinson's disease]. PMID- 1931255 TI - [Gait disorders of Parkinson's disease--'marche a petits pas', frozen gait and apraxia of gait]. PMID- 1931256 TI - [Cognitive impairment in Parkinson's disease]. PMID- 1931257 TI - [New anti-parkinsonian drugs]. PMID- 1931258 TI - [Inventions for preservation of hormonal function in long-term culture of human functioning pituitary adenoma]. AB - This study was designed to establish in vitro model systems in human hormone producing pituitary adenomas that are analogous to the in vivo cellular environment. Mechanically dispersed cells composed of single cells and aggregates from 6 pituitary adenomas (3 GH producing adenomas and 3 prolactinomas) were cultured on microporous membrane cell culture inserts (Millicell-CM) coated with Basement Membrane Matrigel for up to 6 months. Growth hormone or prolactin in the medium was measured during the culture, and morphological feature in vitro was also compared with that of the original tumor at intervals. Not only single cells but also large aggregated cells which usually float in the medium when seeded on conventional plastic, were flattened and firmly attached to coated microporous membrane under the control of medium volume in culture. In both type adenomas, especially prolactinomas, surviving aggregated adenoma cells revealed preserved hormone activity and no dedifferentiation of cell characteristics after 6 months in culture. Particularly during the first 2 months in culture, close similarity existed between in vivo and in vitro conditions with regard to cell morphology and hormone release. These results indicate that this new culture method may further aid the investigation of in vitro cellular structure and function in human pituitary adenomas under conditions which closely mimic the in vivo cellular environment. PMID- 1931259 TI - [Functional relationships between the cerebrum and cerebellum or the cerebral cortex and deep gray matter in normal subjects and patients with Alzheimer's type dementia]. AB - Since the various parts of the central nervous system are functionally interconnected, functional relationships between one region and another would be expected to be present. We investigated whether functional relationships between the cerebrum and cerebellum or between the cerebral cortex and deep gray matter exist in normal subjects and patients with Alzheimer's type dementia (AD), using the indicator of asymmetry in cerebral blood flow. Eighteen normal subjects (average age: 72.6 +/- 11.4 years) and 21 patients with AD (average age: 75.5 +/- 8.1 years) were studied in the resting state using SPECT with 123I-IMP. The asymmetry index (AI) of blood flow for matched left-right regions of interest was calculated as follows: AI = (R-L)/(R + L)/200(%) (R: right side, L: left side). For both the normal and AD groups, we found a negative correlation between AI in the cerebrum and AI in the cerebellum. The AIs of widespread cortical subregions, except the occipital cortex, were significantly correlated with AI in the cerebellum in the AD group. On the other hand, the only significant correlation found in normal subjects was between the AIs of the frontal cortex and cerebellum. A positive correlation between the AIs in the cerebral cortex and deep gray matter was observed in both the normal and AD groups. Though only the upper frontal and parietal cortices showed significant correlations with the deep gray matter in normal subjects, more extensive cortical subregions showed significant correlations in AD patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931260 TI - [A case of pituitary adenoma with simultaneous secretion of TSH and GH detected by double immunostaining method]. AB - A rare case of simultaneous hypersecretion of thyroid stimulating hormone (TSH) and growth hormone (GH) in a pituitary adenoma is reported. A 59-year-old male complaining of general fatigue, dyspnea on exertion and finger tremor was admitted. Examination on admission, he revealed with hyperthyroidism and hypersecretion of TSH and thyroid hormones. Administration of TRH did not further increase serum TSH level, and administration of T3 also had no effect on TSH secretion. CT scan showed a pituitary macroadenoma 13mm in diameter. MRI demonstrated a homogenously hypointense mass with Gd-DTPA enhancement in the left side of the sella turcica. The entire chromophobic adenoma was removed by trans sphenoidal surgery. Immunostaining of the specimen showed that the cytoplasm of the adenoma cells was positive for both TSH and GH. Double immunostaining using avidin-biotin-peroxidase complex (ABC) method and immunogold silver staining (IGSS) method, showed that the adenoma cells had been secreting both GH and TSH at the same time. After the adenomectomy, the hyperthyroidism disappeared, and all altered indicators of pituitary function returned to normal. PMID- 1931261 TI - [A case of an intracranially located esthesioneuroepithelioma]. AB - A 1-year-8-month-old boy was admitted to our service on September 30, 1986, complaining of nausea, vomiting and consciousness disturbance lasted for about 2 weeks. In CTs, right frontal cystic mass which was homogeneously enhanced by contrast media was revealed. Neither hypervascularity nor tumor staining were seen angiographically. On October 9, 1986, total removal of the tumor was performed. The tumor was located extracerebrally in the right anterior cranial fossa, but was covered with arachnoid membrane. The tumor showed tight adhesion with falx cerebri, particularly at crista galli where an invasive infiltration was seen. Light microscopic examination demonstrated oval or spherical small cells arranged multilobularly with rosette like formation and numerous mitoses. Ultrastructurally, cilia, microvilli and junctional complexes were observed. No dense-cored secretory granules were found in the tumor cells. Immunohistochemical study on this tumor showed negative NF and GFAP; positive NSE, S-100, vimentin and keratin. From these findings, the tumor was diagnosed as esthesioneuroepithelioma. Postoperatively, irradiation and chemotherapies were also performed, and the patient showed uneventful course. On January 31, 1987, he was discharged on his foot, and no recurrent or metastatic signs could be found until the end of March of 1990. PMID- 1931262 TI - Cardiovascular effects of cocaine abuse. AB - According to the 1988 National Household Survey conducted by the National Institute on Drug Abuse, cocaine use among the total population has decreased. This same survey also reported an increase in cocaine use among chronic abusers of the drug. As cocaine use has increased among the abuser population, so has the number of emergency room admissions for cocaine-related complaints; moreover, these patients were admitted with primarily cardiovascular complaints. It is important for the nurse practitioner to recognize the cardiotoxic effects of cocaine abuse. Cocaine abuse should be part of the differential diagnosis in patients with cardiovascular complaints. PMID- 1931263 TI - Planning for decisional incapacity. The nurse practitioner's role. AB - Decisional incapacity is the inability to make decisions for oneself caused by mental or physical impairment. With technologic advances in health care and the growing proportion of elderly in American society, the problem of decisional incapacity occurs more frequently. In the past, medical decision making was based on the principle of beneficence, and the judgment of others was used to determine medical interventions. The current trend is to base decisions as much as possible on the principle of patient autonomy. Advance directives allow for the greater use of this principle. The primary care nurse practitioner (NP) can take an active role in promoting patient autonomy by helping the adult patient plan for decisional incapacity. By including the value history as a routine part of the health history, the NP can help patients identify their beliefs, values, and attitudes about health care. This documented value history can then be used to provide evidence of a patient's wishes should he or she become decisionally incapacitated. PMID- 1931264 TI - A tree of impact model. Evaluation of consequences of repeal of the abortion law on teenage pregnancy. AB - Teenage pregnancy is a complex issue in the current sociopolitical milieu. The enactment of abortion laws adds to the complexity of the problem, involving moral and ethical issues, as well as social, economic, and health status consequences that should be considered in the development of legislation surrounding this issue. The tree of impact diagram is a mechanism for forecasting possible consequences of abortion laws. Historical, social, developmental, economic, and legal forces are considered in creating the tree of impact in relation to the health and well-being of teenage mothers and their children. PMID- 1931266 TI - Tourette's syndrome. PMID- 1931265 TI - Adolescent health concerns: a comparison of adolescent and health care provider perceptions. AB - The purpose of this study was to ascertain adolescent perceptions of health concerns and to contrast the health care provider perceptions of adolescent concerns. The student sample consisted of 179 students from the 9th, 10th, and 11th grade in a 2,000-student suburban high school. The health care provider sample consisted of 74 physicians, nurse practitioners, and school nurses. The largest number of students reported concerns about AIDS, schoolwork, making friends, sex, discrimination, and dental problems. Additionally, menstruation, violence, rape, abuse, pregnancy, sadness, and obesity were of concern to a greater number of female than male students. Homosexuality, sex, auto accidents, and low weight were of concern to a greater number of male than female students. The findings of this study support the following conclusions: (a) Adolescents have more diverse health concerns with greater magnitude than expected by health care providers; (b) health care providers underestimate adolescent psychological and social health concerns; (c) female adolescents were more concerned about their health and more concerned about gender-specific and violent issues than males; (d) women's health care providers are unaware of female adolescent concern about violent acts against women. PMID- 1931267 TI - Healthy beginnings: proposed legislation for a back-to-basics approach to reducing infant mortality. PMID- 1931268 TI - Initiating a gerontological nurse practitioner practice in long-term chronic care. PMID- 1931269 TI - Back to school signals "head lice season". PMID- 1931270 TI - Combining the role of the nurse practitioner and the community health nurse. An educational model for implementing community-based primary health care. AB - With increasing health care costs, public health agencies and other institutions have a critical need for master's-prepared nurses who can provide health care for common health problems of individuals and families but also assess, plan, intervene, and evaluate the needs of communities. This article describes the development of a nursing master's degree program to meet that need which combines the traditional roles of the nurse practitioner and the community health nurse. The program is based on the global concept of primary health care as defined by the World Health Organization, which includes more emphasis on economic, political, environmental, and social factors. PMID- 1931271 TI - [Current techniques of manual instrumentation in endodontics]. PMID- 1931272 TI - [Oral hygiene program on the left bank of the Nervion: its effect on gingivitis]. AB - The effect of monthly professional tooth clearing over gingivitis, without instructions of oral hygiene, was evaluated in a group of 69 children whose ages were from 6 to 12, in the left side of Nervion. The plaque index, PI, and gingival index GI, were registered in the initial exam, al 6, 12, 18 and 24 months. For the test group, the value of the plaque index in the initial exam was 1.57 and for the control group was 1.64. In totally 20 sessions, to the groups test were applied professional monthly clearing, followed by the "aplicacion topica de fluoruro sodico". After 6 months the study began, the plaque index for the group text was 1.18 and for the control group 1.30. In the same way, the gingival index turned out to be 0.21 for the text and 0.37 for the control. The final results gave a plaque index for the text group of 1.01 and for the control group 1.32 and the gingival index 0.29 for the test group and 0.71 for the control. This leads to the thinking that it's enough for children a monthly dental plaque removal, to prevent the develop of the gingivitis. PMID- 1931273 TI - 'Primary dental care--a higher profile in the NHS'. PMID- 1931274 TI - NHS dentistry--a monopoly. PMID- 1931275 TI - 'The oral health status, dental needs and factors affecting utilisation of dental services in Asians aged 55 years and over, resident in Southampton'. PMID- 1931276 TI - BDA Oxford Conference Case: an update. PMID- 1931277 TI - Burrowing resorption of third molars. PMID- 1931278 TI - Some factors affecting retention forces with the use of denture fixatives in vivo. AB - Using the UCL retentiometer, the effect of three proprietary denture fixatives has been clinically investigated in 14 dentate subjects wearing mucosal-borne acrylic palatal plates over periods of 6 hours. The results showed that retention forces with saliva for the well-fitting plates were significantly better when compared with the forces for the ill-fitting plates. A substantial improvement in retention on all occasions was seen for both types of plate after the application of fixatives. An interesting observation of this study was that the use of paste and liquid fixatives rendered the ill-fitting plates as retentive as the well fitting plates with the same fixatives. The test fixatives, however, showed significant differences regarding the onset and duration of action, depending on their physical formulation. The paste and liquid fixatives were found to have more delayed action than the powder fixative, but maintained the improved retention for a post-insertion period of more than 6 hours for both well-fitting and ill-fitting plates. Investigation of the effect on retention of different quantities of fixatives showed that larger amounts were associated with greater retention. The findings of these studies predict that a single application of 0.6 ml of either the paste or liquid fixatives used in this study is a recommended quantity which would provide and maintain the desirable retention for more than 6 hours in most cases of well-fitting complete dentures and those with retention problems. The powder fixatives though very effective immediately, would, however, require repeated applications every 3 hours or so, depending to some extent upon the use that the product will be put to. PMID- 1931279 TI - General practitioners' perceptions of the effects of a distance learning programme. AB - A postal/telephone survey of 400 general dental practitioners working in the Greater Glasgow and Lanarkshire Health Board areas was carried out between May and September 1990. The aims were to monitor any changes in the use of sealant restoration techniques in the last year, to investigate the practitioners' perception of the effects of a distance learning programme on their techniques and to provide data on the use of the techniques in the final months of the 'old contract'. A response rate of 66.7% was achieved. Eighty-eight per cent of the group were placing sealant restorations. Dentists' perceptions of the impact of the distance learning programme were encouraging. In key areas of practice, 16 44% of the group reported changes in their clinical techniques as a result of reading the programme. PMID- 1931280 TI - Carcinoma arising in cyclosporin-induced gingival hyperplasia. AB - A patient with intra-oral squamous cell carcinoma arising in an area of cyclosporin-induced gingival hyperplasia associated with a renal transplant is presented. This appears to be the first reported case of its kind. Subsequently, the patient developed a carcinoma of the lateral margin of the tongue, with metastasis to the deep cervical lymph nodes. The incidence and types of malignancy following conventional immunosuppressive and cyclosporin therapy are briefly reviewed. Long-term frequent follow-up of cyclosporin-treated patients is recommended to facilitate early diagnosis of such lesions. PMID- 1931281 TI - 'Gobsmacking grins'. AB - Over the past decade, marked reductions have been recorded in dental caries levels for teenage children in Somerset. These have been documented in BASCD Regional Surveys and reflect a national picture of improving dental health. Nevertheless, over the same period of time, the level of gingival health for Somerset teenagers has remained relatively static. PMID- 1931282 TI - 'Provision for endodontic therapy within the GDS'. PMID- 1931283 TI - 'Radiopaque substances in denture manufacture'. PMID- 1931284 TI - 'AIDS testing for health care workers'. PMID- 1931285 TI - 'The hospital-based dental specialties'. PMID- 1931286 TI - 'A denture of a lifetime'. PMID- 1931287 TI - Potassium chloride dentrifrice as a desensitizing agent. PMID- 1931288 TI - The case for specialisation in general dental practice. PMID- 1931289 TI - 'Laser success'. PMID- 1931290 TI - Teamwork--supplement number 10. PMID- 1931291 TI - Dental staff sexual behaviour. PMID- 1931292 TI - 'Orthodontic headgear related to allergic contact dermatitis'. PMID- 1931293 TI - Guided tissue regeneration. AB - One of the main goals of periodontal therapy is the predictable regeneration of the periodontium by allowing repopulation of periodontal ligament cells into the wound area after surgery and preventing the colonisation of the exposed root surface with epithelial, gingival, and bone cells. In order to achieve this, emphasis has been placed on the use of barrier materials in the form of semipermeable membranes which are interposed between the mucoperiosteal flap and the bone and tooth surfaces during surgery. This technique is known as 'guided tissue regeneration' (GTR) and this article looks at the theory and practice of GTR, as well as reviewing the use of non-resorbable membrane materials such as expanded polytetrafluor-ethylene and ethyl cellulose, and resorbable materials such as collagen and polylactic acid. PMID- 1931294 TI - Glove use in clinical practice: a survey of 2000 dentists in England and Wales. AB - Attitudes to glove wearing by dentists practising within the NHS Regulations were tested by means of a questionnaire distributed to 2000 dentists in England and Wales. The response was 76.5%. The results indicate that 68% of the respondents wore gloves routinely for all patients and procedures, 3% never wore gloves, while the remainder (29%) wore gloves for only selected patients or selected procedures. Reasons given for not wearing gloves routinely included problems of comfort, loss of tactile sensation and the risk of cross-infection, which was perceived to be small. Of the routine glove wearers, only 12% changed gloves between patients, cost being considered to be a factor by 57% of respondents who used gloves for more than one patient. The results indicate that the respondents practising and personal details had an influence on the pattern of glove wearing, with single-handed practitioners and those who graduated before 1979 being less likely to wear gloves routinely. Comparison with the findings of earlier studies of similar type suggest that there is increased awareness in the dental profession of the necessity for glove wearing, but that there is still a need to encourage routine glove use, especially amongst certain groups of GDPs. PMID- 1931296 TI - Long in the tooth: witness for the profession. PMID- 1931297 TI - Electronic claims made easy. PMID- 1931295 TI - The incidence and distribution of oral lesions in patients with Darier's disease. AB - Darier's disease is an uncommon autosomal dominant genodermatosis that may be accompanied by oral lesions. The incidence and distribution of oral manifestations was studied in 24 patients with cutaneous Darier's disease. Oral lesions comprising whitish papules of varying severity were present in 12 patients, with the palate being the most common site affected, followed by gingiva, buccal mucosa and tongue. Generally, the severity of the oral lesions paralleled that of the skin condition. Seven patients (30%), six of whom also had oral mucosal involvement, reported intermittent parotid swelling. Parotid sialograms of two patients revealed strictures in the main ducts, suggesting an obstructive aetiology. PMID- 1931298 TI - The effect of post space preparation on the apical seal of root canal obturated teeth. AB - The dental literature is contradictory about the quality of the apical seal as it relates to the length of remaining gutta-percha following post-space preparation. The purpose of this study was to compare apical leakage with varying remaining lengths of gutta-percha in an in vitro system. Fifty disarticulated single canal human mandibular premolar teeth were used in five experimental groups. All root canals were prepared 1 mm short of the apical foramen through a size 50 k-file and sequentially flared through a size 70 k-file. Four groups were obturated using gutta-percha with lateral condensation and Roth's 801 Elite Grade root canal sealer. Post-space preparation was accomplished by removing gutta-percha with heated pluggers so that the lengths of the remaining filling varied by increments of one millimeter between 3 and 7 mm. Specimens were covered with enamel paint leaving only the apical foramen exposed. All roots were then submerged in 1 percent methylene blue dye for two weeks, sectioned longitudinally, and measured for depth of dye penetration. No significant difference was found between the 4 and 5 mm groups or between the 6 and 7 mm groups. Significant difference (p less than .05) in leakage did exist between the 3, 4-5, and 6-7 mm groups, showing the least in the latter groups. The best apical seal was obtained when the maximum of 6 mm of gutta-percha remained. PMID- 1931300 TI - The inverted precision dowel attachment. PMID- 1931301 TI - Paths to concept development in nursing diagnosis. AB - Three pathways to diagnostic concept development are proposed. Principles and methods that operate on each path are presented. Careful concept development contributes to precise diagnostic labels and to the advancement of nursing science. PMID- 1931299 TI - Avoiding periodontal lawsuits. PMID- 1931302 TI - Examination of nursing diagnoses for adults hospitalized with acquired immunodeficiency syndrome, 1982-1990. AB - The literature on nursing care of the hospitalized adult with acquired immunodeficiency syndrome (AIDS) from 1982 to the present was examined, and 16 formal care plans were extracted. The nursing care plans were examined for commonalities of identified nursing diagnoses, which were then tabulated according to frequency. Analysis of the types of problems addressed shows that five of the nine highest-frequency problems were physiologic (altered nutrition: less than body requirements, respiratory problems, impaired skin integrity, diarrhea, potential for infection). The other four problems were cognitive (altered thought processes), safety (potential for injury), social (social isolation), and a combination of physiologic and cognitive (pain). Validation of nursing diagnoses is needed as a solid foundation for nursing intervention research in the care of patients with AIDS. PMID- 1931303 TI - Evaluation of admission nursing diagnoses. AB - Despite the interest and research in nursing diagnosis, few studies have examined the incidence and quality of the diagnoses. Specifically, a lack of knowledge exists regarding what nursing diagnoses are formulated on a patient's admission to the hospital. Data from the charts of 33 adult orthopedic patients were evaluated for the type, frequency, and quality of admission nursing diagnoses. Of the 106 nursing diagnoses written, approximately two-thirds were on the accepted list of the North American Nursing Diagnosis Association (NANDA) at the time of the study (1988). Alteration in comfort was the most prevalent diagnostic label. The quality of the diagnoses was evaluated using Ziegler's (1984) tool. Only one diagnosis, potential alteration in skin integrity related to bedrest, met all 12 criteria. Nurses showed more difficulty in correctly identifying the etiology component than the response component of the diagnostic statement. Factors that affect the quality of nursing diagnoses and the need for tool refinement are discussed, and research recommendations are made. PMID- 1931304 TI - Analysis of a human phenomenon: self-concept. AB - This analysis of self-concept includes an examination of definitions, historical perspectives, theoretical basis, and closely related terms. Antecedents, consequences, defining attributes, and a definition were formulated based on the analysis. The purpose of the analysis was to provide support for the use of the label "self-concept" as a broad category that encompasses the self-esteem, identity, and body-image nursing diagnoses within Taxonomy I. This classification could allow the use of a broad diagnostic label to better describe conditions that necessitate nursing care. It may also further explain the relationships between and among those diagnoses that describe human responses to disturbance of any component of the self-concept. PMID- 1931305 TI - From taxonomy I to taxonomy II. AB - Taxonomic development in nursing, although still in its infancy, is progressing. Taxonomy development has moved beyond subjective placement of diagnoses into categories based on an "expert" opinion alone. The taxonomy of nursing diagnoses is entering a new era whereby the assumptions and classification rules for Taxonomy I--Revised are being investigated. Alternative taxonomic structures require careful scrutiny and comparison to establish whether one structure will meet the needs of the profession or whether multiple structures of nursing diagnoses relative to outcomes are required. As members within the discipline become more sophisticated in approaches to taxonomic development, methods of handling taxonomic problems, such as varying levels of abstraction and taxonomic affinity, will be discerned. PMID- 1931306 TI - The see-through nurse is a matter of history. PMID- 1931307 TI - Development and content validity testing of a comprehensive classification of diagnoses for pediatric nurse practitioners. AB - Pediatric nurse practitioners (PNPs) need an integrated, comprehensive classification that includes nursing, disease, and developmental diagnoses to effectively describe their practice. No such classification exists. Further, methodologic studies to help evaluate the content validity of any nursing taxonomy are unavailable. A conceptual framework was derived. Then 178 diagnoses from the North American Nursing Diagnosis Association (NANDA) 1986 list, selected diagnoses from the International Classification of Diseases, the Diagnostic and Statistical Manual, Third Revision, and others were selected. This framework identified and listed, with definitions, three domains of diagnoses: Developmental Problems, Diseases, and Daily Living Problems. The diagnoses were ranked using a 4-point scale (4 = highly related to 1 = not related) and were placed into the three domains. The rating scale was assigned by a panel of eight expert pediatric nurses. Diagnoses that were assigned to the Daily Living Problems domain were then sorted into the 11 Functional Health patterns described by Gordon (1987). Reliability was measured using proportions of agreement and Kappas. Content validity of the groups created was measured using indices of content validity and average congruency percentages. The experts used a new method to sort the diagnoses in a new way that decreased overlaps among the domains. The Developmental and Disease domains were judged reliable and valid. The Daily Living domain of nursing diagnoses showed marginally acceptable validity with acceptable reliability. Six Functional Health Patterns were judged reliable and valid, mixed results were determined for four categories, and the Coping/Stress Tolerance category was judged reliable but not valid using either test. There were considerable differences between the panel's, Gordon's (1987), and NANDA's clustering of NANDA diagnoses. This study defines the diagnostic practice of nurses from a holistic, patient-centered perspective. It is the first study to use quantitative methods to test a diagnostic classification system for nursing. The classification model could also be adapted for other nurse specialties. PMID- 1931308 TI - Setting up a dental health exhibition. PMID- 1931309 TI - Dental implants. PMID- 1931310 TI - Training physicians to care for the dying. AB - PROBLEM: The education of medical students and house staff regarding management of death and timely discussions of death with patients and families has been deficient, leaving physicians ill-equipped to provide appropriate care to dying patients. METHOD: We propose a five-pronged curriculum in terminal care to be ongoing from medical school through postgraduate training. This program includes: Clinical skills--including pain and symptom management, prognostication and care in various settings; Communication skills--including listening and how to discuss bad news with patient and family; Psychosocial issues; Administrative/management and team interaction, and Bioethical issues, including DNR and living wills. CONCLUSION: It is hoped that such training will teach physicians to accept death as inevitable, to recognize and acknowledge the state of dying and, finally, to understand that appropriate care includes appropriate death, which is one arrived at with minimal suffering, with minimal social and emotional impoverishment, with preservation or restoration of important relationships and with resolution of residual conflicts. PMID- 1931311 TI - Rural hospices: strategic planning for expansion. PMID- 1931312 TI - Why start a hospice: is the need for a hospice real ... or perceived? PMID- 1931313 TI - A statement of assumptions and principles concerning education about life threatening illness, death, dying, and bereavement for volunteers and non professionals. International Work Group on Death, Dying and Bereavement. PMID- 1931314 TI - Toward an understanding of complicated grief: a comprehensive overview. PMID- 1931317 TI - My year in hospice. PMID- 1931315 TI - Intimacy: the cornerstone of caring. PMID- 1931316 TI - Hospice development: insights from four models. 4. PMID- 1931318 TI - Symptom character and prevalence during cancer patients' last days of life. PMID- 1931319 TI - My mother's legacy. PMID- 1931320 TI - Hospice-assisted deaths in a forensic facility: a comparison of patient reactions. PMID- 1931321 TI - Clinical clowning: humor in hospice care. PMID- 1931322 TI - Accumulated loss phenomenon among hospice caregivers. PMID- 1931323 TI - Support group for those affected by AIDS in the family. PMID- 1931324 TI - Documentation: how to prove you did what you say you did. PMID- 1931325 TI - Self-esteem and hospice: applying principles to practice. AB - Maintenance of a healthy degree of self-esteem is essential to the goal of helping patients and their significant others to live as fully as possible. It is important for hospice caregivers to be aware of factors which tend to diminish self-esteem in hospice care recipients as well as in themselves. A knowledge of basic principles about self-esteem and the application of interventions based on these principles can aid in the preservation and enhancement of self-esteem in hospice caregivers and recipients. PMID- 1931326 TI - AIDS and hospice. AB - Which AIDS patients should be admitted to hospice programs? Many health care professionals feel that any anti-viral drug or treatment directed against the opportunistic infections characteristic of AIDS to be incompatible with hospice philosophy. Others argue that inclusion of AIDS patients blurs the distinction between hospice and community service programs. We argue that achieving consensus on this issue is best served by focusing on the defining characteristic of hospice programs--the care of the dying. Consensus is not served by dwelling on the specific palliative or supportive measures used to achieve the hospice goal. We suggest a framework by which AIDS patients may be accommodated in existing hospice programs while maintaining hospice program integrity. It is further suggested that these may be used for the consideration of any patient for hospice care. PMID- 1931327 TI - Using a community networking approach in a bereavement program. AB - This paper reviews the history of St. Anthony's Hospice and Life Enrichment Program. St. Anthony's provides bereavement counseling and death education to the community using a networking approach involving the educational, religious, social, and mental health organizations in the area. At present, this model features a church satellite program, grief recovery and anticipatory grief seminars, on-going bereavement support and social support groups, volunteer speakers' bureau, a volunteer staffed bereavement team, and training of psychology, nursing, and medical students. PMID- 1931329 TI - A qualitative retrospective study of coping strategies of newly widowed elderly. Effects of anticipatory grieving on the caregiver. AB - Findings of a qualitative retrospective study of coping strategies of newly widowed elderly are presented. The focus is on effects of anticipatory grieving on the caregiver before the spouse's death as reported by the widowed partner following the death. Most frequent and troubling problems were reported as loneliness, social isolation, disruption in eating and sleeping patterns and independent decision making. Changes in health status following the death were not as detrimental as expected. Caregivers' health actually improved when those responsibilities were over. Recommendations for hospice care for the caregiver are suggested. PMID- 1931328 TI - Support for grieving children: the Dougy Center and the hospice philosophy. The staff of the Dougy Center. PMID- 1931330 TI - Controlled-release oral morphine. PMID- 1931331 TI - From theory to practice: laying the foundations of a hospice world. 5. PMID- 1931332 TI - Billing, reimbursement and other mystic arts. PMID- 1931333 TI - [Quality in nursing. Self-regulation demonstrates the will for accountability]. PMID- 1931334 TI - [Common Market, EEC and nursing's educational status]. PMID- 1931335 TI - [Quality in nursing. Regulation of the profession--an important form of quality assurance]. PMID- 1931336 TI - [The use of hypnotics. Sleep hygiene--introduction of a "sleep hygiene program" in a psychiatric department]. PMID- 1931337 TI - [Quality in nursing. Quality assurance in an international perspective]. PMID- 1931338 TI - Bureaucracy and creativity: a synergistic approach. PMID- 1931339 TI - Role of nursing in constructing a new framework for health care delivery. PMID- 1931340 TI - The impact of changes in capital reimbursement. PMID- 1931341 TI - Creativity in the new nurse manager. PMID- 1931342 TI - Restructuring, redesign: laying the groundwork. PMID- 1931343 TI - Structure of the starch granule--a curved crystal. AB - A structure model of the molecular arrangement in native starch proposed earlier is further considered, with special regard to the lateral packing of cluster units. The amylopectin molecules are radially distributed, with branches concentrated in clusters. Within each cluster the polyglucan chains form double helices which are hexagonally packed. The clusters form spherically concentric crystalline layers with amylose in an amorphous form acting as a space-filler. A translational mechanism for the change of helical direction at boundaries between clusters is proposed which can account for variations in the curvature of the concentric layers. The model is related to X-ray diffraction data and optical birefringence, considering dissembly at gelatinization. The structure is also discussed in relation to biosynthesis. Some aspects of gelatinization, such as the recent glass-transition approach, are then considered. PMID- 1931344 TI - The genetics of hypertrophic cardiomyopathy. PMID- 1931345 TI - Digital coronary angiography: the new gold standard? PMID- 1931346 TI - Verapamil and morphine. PMID- 1931347 TI - Induction of a reduction in haemoglobin concentration by enalapril in stable, moderate heart failure: a double blind study. AB - OBJECTIVE: To study the long term effects (12 weeks) of enalapril on central haemodynamic function and on arterial oxygen content and its determinants- haemoglobin concentration and oxygen saturation--in patients with stable moderate heart failure. DESIGN: Double blind placebo controlled randomised study. PATIENTS: 17 patients with stable moderate heart failure caused by dilated cardiomyopathy which was treated with diuretics and digoxin. METHODS: Central haemodynamic function, arterial oxygen content, arterial haemoglobin concentration, and arterial oxygen saturation were measured at rest and during submaximal exercise. Plasma volume and total body haemoglobin were determined at rest. RESULTS: With enalapril treatment heart rate, pulmonary capillary wedge pressure, mean arterial pressure, and systemic vascular resistance decreased significantly both at rest and during submaximal exercise. Cardiac output did not change at rest but tended to increase (p = 0.06) during submaximal exercise. Arterial oxygen saturation remained unchanged while haemoglobin concentration and arterial oxygen content were significantly reduced. Total body haemoglobin was significantly reduced but the plasma volume remained unchanged. At rest, the reduction in arterial oxygen content resulted in a significantly reduced mixed venous oxygen content. However, during submaximal exercise the increase in cardiac output fully compensated for the reduction in arterial oxygen content and this effect was indicated by the unaltered mixed venous oxygen content. No changes were found in the placebo group after twelve weeks. CONCLUSIONS: Enalapril unloads the heart and reduces haemoglobin concentration. During submaximal exercise, the improvement in systemic blood flow was counterbalanced by this negative effect on the oxygen carrying capacity and systemic oxygen delivery was unchanged. PMID- 1931348 TI - Genesis of Still's murmurs: a controlled Doppler echocardiographic study. AB - OBJECTIVE: The origin of innocent systolic murmurs is uncertain. This study was designed to evaluate the relative contribution in the same subjects of the main factors implicated in the genesis of vibratory innocent systolic murmurs--that is, the presence of left ventricular bands and increased left ventricular flow indices--and to examine evidence for turbulence in relation to these findings. PATIENTS: 40 children with innocent systolic murmurs and 40 paired controls without murmurs were matched for age and body surface area. DESIGN: These subjects were examined prospectively by cross sectional echocardiography with pulsed and continuous wave Doppler and colour flow mapping. SETTING: A tertiary referral centre for paediatric cardiology. RESULTS: Left ventricular bands were significantly more prevalent in patients with innocent murmurs (70%) than in controls (48%) but only if apical bands were included (p = 0.039). Cases had significantly higher aortic peak flow velocities (p less than 0.001), flow integrals (p = 0.001), and stroke volumes (p = 0.014), and significantly lower heart rates (p = 0.033) than controls. There were no significant differences between cases and controls in mean aortic diameter, cardiac output, or ejection fraction. There was no evidence of turbulence in the left ventricle or outflow tract in any individual but curvilinear periodic vibrations and audible "whoops" were detected in the left ventricle by pulsed wave Doppler echocardiography. These were significantly more common in cases than controls (p less than 0.01) but were not related to the presence of bands. CONCLUSIONS: Innocent systolic murmurs were unrelated to aortic size but they were strongly associated with higher aortic flow volume and velocity, with relative bradycardia, and with evidence of vibratory phenomena in the left ventricle. The role of left ventricular bands remains uncertain. PMID- 1931349 TI - Moderate hypothermia in the management of resistant automatic tachycardias in children. AB - BACKGROUND: Automatic focus tachycardias are often resistant to electrical and pharmacological treatment. Moderate systemic hypothermia (32-34 degrees C) may reduce the tachycardia rate in children with His bundle tachycardia after cardiac surgery. METHODS: The case notes of seven children with automatic focus tachycardias treated with hypothermia were reviewed. Six had His bundle tachycardia after cardiac surgery and one had ectopic atrial tachycardia; all had signs of low cardiac output. RESULTS: Hypothermia led to a reduction in heart rate in all patients (from 211 (28) (mean (SD] to 146 (5) beats/minute, p less than 0.001), with rises in systolic blood pressure (from 74 (14) mm Hg to 97 (10) mm Hg, p less than 0.01) and hourly urine output (from 0.5 (0.4) ml/kg to 4.6 (2.8) ml/kg, p less than 0.02). No direct adverse effects were noted. The arrhythmia did not resolve in three children, who died (two with His bundle tachycardia after Fontan procedures and one with ectopic atrial tachycardia); the other four regained sinus rhythm which was maintained at follow up of 3-13 (mean 9) months. CONCLUSIONS: Moderate systemic hypothermia led to slowing of the arrhythmia rate and an improvement in cardiac output in patients with resistant automatic focus tachycardias. It can be used to improve the haemodynamic condition while other measures of arrhythmia control are being pursued or until spontaneous recovery of normal rhythm. PMID- 1931350 TI - Atrial pacing as an adjunct to the management of post-surgical His bundle tachycardia. AB - OBJECTIVE: To examine the benefits of restoring atrioventricular synchrony to children with His bundle tachycardia after operation for congenital heart disease. DESIGN: Review of clinical outcome of adopting the technique of R wave synchronised atrial pacing as an adjunct to the management of His bundle tachycardia from September of 1987 till June of 1990. PATIENTS: Eleven consecutive children (aged between 3 days and 13 years) with haemodynamically significant His bundle tachycardia after cardiopulmonary bypass surgery. INTERVENTIONS: Atrial pacing synchronised either manually or automatically to the R wave of the His bundle tachycardia was implemented so that atrial depolarisation preceded the following R wave by an appropriate PR interval. RESULTS: An immediate and sustained increase in mean systemic blood pressure (average 15 mm Hg, range 6-30 mm Hg) was seen with the onset of atrial pacing in 10 of the 11 children. One child, who had undergone a Fontan procedure, developed atrial flutter shortly after the onset of atrial pacing and required direct current cardioversion. Four children died. Of the seven survivors, six have sustained sinus rhythm which returned between two and 10 days after the onset of tachycardia. One of the survivors has severe neurological impairment attributed to a period of low cardiac output during tachycardia; the others are alive and well. In those children who did badly the mean time between arrhythmia occurrence and the start of atrial pacing or cooling or both was nine hours; in those who did well it was one hour. CONCLUSIONS: Atrial pacing synchronous with the His bundle is a useful adjunct in the management of children with His bundle tachycardia after surgery for congenital cardiac disease. PMID- 1931351 TI - Dynamics of ventricular repolarisation in the congenital long QT syndromes. AB - Patients with congenital QT interval prolongation are at risk of ventricular arrhythmias and sudden death. It has been suggested that the susceptibility to arrhythmias in these syndromes may be related to the abnormal dynamics of ventricular repolarisation. The dynamics of ventricular repolarisation, including assessment of the effect of changing heart rate on the QT interval and the duration of the right ventricular monophasic action potential, were studied in eight patients with congenital long QT syndromes. The effects of altered sympathetic tone on these dynamics were investigated with isoprenaline, propranolol, and left stellate ganglion block. The rate adaptation of the QT interval was abnormal in only a few patients and in some patients this feature may be related to the severity of the condition. These abnormalities may be exaggerated by isoprenaline and lessened by propranolol and left stellate ganglion block. Monophasic action potential dynamics were normal in all patients. The hypothesis that impaired QT rate adaptation may play a role in the genesis of ventricular arrhythmias in these syndromes is not, in general, supported by the present data. However, in patients with impaired adaptation the normalisation of QT dynamics after beta blockade and left stellate ganglion block was consistent with the efficacy of these forms of treatment. PMID- 1931353 TI - Conservative surgery in multiple cusp involvement in tricuspid valve endocarditis. AB - Tricuspid and mitral valve endocarditis caused by Staphylococcus epidermidis in a 57 year old previously healthy man with no history of drug abuse presented as bi ventricular failure and multiple episodes of pulmonary emboli. He was treated for four weeks with intravenous antibiotics and had serial echocardiographic assessment of the vegetation on the tricuspid valve. This was followed by mitral valve replacement, local excision of vegetation from all the three cusps of the tricuspid valve, and autologous pericardial reconstruction of these cusps with functional assessment by perioperative transoesophageal echocardiography. Postoperative cardiac function was excellent and serial echocardiographic assessment confirmed satisfactory tricuspid valve function. This is believed to be the first recorded case in which autologous pericardial repair was used to reconstruct all the three cusps in a tricuspid valve after excision of vegetations. PMID- 1931352 TI - Influence of colour Doppler echocardiography on the ultrasonic assessment of congenital heart disease: a prospective study. AB - OBJECTIVE: To evaluate the additional information provided by colour Doppler in the ultrasonic assessment of congenital heart disease. PATIENTS AND METHODS: A prospective study of 215 children (age range 1 day-16 years) presenting with clinical signs of congenital heart disease. RESULTS: Colour Doppler was essential for the diagnosis of an anomalous left coronary artery and altered the management of a patient initially diagnosed as having cardiomyopathy. Colour Doppler provided extra information, but without major impact on management, in the following: the diagnosis of ventricular septal defects associated with other defects, of multiple ventricular septal defects, of anomalous pulmonary venous drainage, and of mild mitral regurgitation; the demonstration of site of coarctation, of stenotic or hypoplastic pulmonary artery branches, of unobstructed flow through a right atrial membrane, and of left ventricle to right atrium regurgitation; the assessment of the width of the duct and of flow through the patent foramen ovale in transposition and tricuspid atresia; the differentiation of pulmonary atresia from critical pulmonary stenosis and the measurement of maximum velocity of tricuspid regurgitation. CONCLUSIONS: Ideally all patients should undergo colour Doppler studies before cardiac surgery to ensure a more accurate diagnosis. However, since the additional information provided does not affect the management in most patients, machines without colour Doppler can provide a satisfactory service in paediatric cardiology centres in countries where resources are limited. PMID- 1931354 TI - Double partitioning of the left atrium: a previously unreported echocardiographic finding in a case in which transoesophageal echocardiography aided operative resection. AB - Precordial echocardiography showed two membranes obstructing pulmonary venous return in the left atrium of a 9 month old infant. This anomaly has not previously been described; therefore transoesophageal echocardiography was performed at the time of surgery. This confirmed the anatomy and aided complete resection of both membranes. Even in small infants transoesophageal echocardiography can provide useful information about complex atrial malformations. PMID- 1931355 TI - Fatal rupture of an unsuspected post-traumatic aneurysm of the thoracic aorta during pregnancy. AB - A 27 year old woman presented during the third trimester of her second pregnancy complaining of chest pain. A chest radiograph showed a large aneurysm arising from the distal part of the aortic arch. She was transferred to the regional cardiothoracic centre but died suddenly on arrival. Necropsy confirmed a ruptured saccular aortic aneurysm arising just distal to the left subclavian artery. A history of a road traffic accident at the age of 12 was obtained from relatives after the patient's death. Vascular and haemodynamic changes in pregnancy may have caused the rupture of this previously silent post-traumatic aortic aneurysm. PMID- 1931356 TI - British Heart Foundation surveys (1987 and 1989) of United Kingdom treatment policies for acute myocardial infarction. AB - Consultant physicians and cardiologists were surveyed early in 1987 and 1989 to document the management policies for the treatment of acute myocardial infarction in United Kingdom hospitals and to assess the influence of major clinical trials on these policies. The response rate to both these surveys was high (84% (1178 physicians) in 1987 and 76% (982 physicians) in 1989). The percentage of physicians that reported using antiplatelet therapy "routinely" in acute myocardial infarction rose from 9% in 1987 to 84% in 1989 while those who reported using it "rarely or never" fell from 42% to 3%. Similarly, "routine" use of fibrinolytic therapy rose from 2% to 68%, and use "rarely or never" fell from 53% to 3%. This increase in the reported use of fibrinolytic therapy was accompanied by greater certainty about its efficacy and relative safety and by a general widening of the indications for its use. The use of other treatments in acute myocardial infarction (for example, the general use of anticoagulants, beta blockers, nitrates, calcium antagonists, or prophylactic antiarrhythmic agents) seemed to change little during this period, although the routine use of coronary angiography and oral anticoagulants after fibrinolytic therapy fell substantially between 1987 and 1989 (from 23% to 4%, and from 24% to 7% respectively). Fibrinolytic and antiplatelet therapy were accepted into the routine management of myocardial infarction during a relatively short period that coincided with the reporting of several positive controlled trial results. Clinical trials have rarely been seen to have had such a great impact on practice. In this case the rapid acceptance of the trial results may have been due to the consistency and reliability of the estimates of the size of the benefits (and risks) of therapy seen in these unusually large studies. PMID- 1931358 TI - Circadian variation in the frequency of onset of chest pain in acute myocardial infarction. PMID- 1931357 TI - Left ventricular filling dynamics during dipyridamole induced myocardial ischaemia. PMID- 1931359 TI - Syndrome X and hyperventilation. PMID- 1931360 TI - Alcohol ablation of atrioventricular conduction. PMID- 1931361 TI - Echocardiographic diagnosis of a ruptured aneurysm of the sinus of Valsalva: operation without catheterisation in seven. PMID- 1931363 TI - Further experiences of Kuntscher's nailing for tibial shaft fractures. AB - We present the experience of managing 429 fractures of the tibia fixed with straight Kuntscher rods. The overall impression is quite encouraging because this method involves a short and easy operation with limited exposure and provides sound fixation. Complications have been negligible. PMID- 1931362 TI - Impending paradoxical embolism: a rare but important diagnosis. PMID- 1931364 TI - Long-term results after implantation of McKee-Farrar total hip prostheses. AB - From 1973 to 1976, McKee-Farrar total hip arthroplasties were performed in the Orthopaedics Department at the Centre of Pulmology. In the present study, only patients with a complete record of radiological changes at the bone/implant or bone/cement interface were evaluated. A series of 81 patients with 100 total hip prostheses in situ according to the Mayo Clinic hip score and 36 patients who had undergone 36 revision operations were studied. The design of the metal cup with metal studs at the outer surface has a favourable effect on the stability of the implant/cement combination: loosening at the implant/cement interface did not occur in any of these cases and there were few cement fractures. In spite of the metal-to-metal combination, abrasion is slight and there is no danger of metallosis. PMID- 1931365 TI - Functional restitution after lower leg fractures. A long-term follow-up. AB - Twenty-five patients with fractures of the lower leg treated by closed reduction and plaster fixation were examined an average of 7 years and 8 months after trauma. The end result was assessed according to the following: (1) The patient's own opinion; (2) clinical examination including comparing range of motion in knee and ankle in the fractured and non-fractured leg, leg length discrepancy, malrotation of the injured extremity and muscle force analysis; (3) radiological examination. All fractures had healed after a mean of 13.4 weeks. Twelve of the 25 patients had no complaints. Subjective and objective assessment of the end results were in good correlation. Only eight patients had remaining radiological displacement, in only one of which it was severe. The slight remaining malpositionings did not influence the final functional result. The muscle force analysis showed that fractures caused by high-energy trauma also brought permanent reduction of muscular strength to the fractured extremity. PMID- 1931367 TI - Results of partial patellectomy. AB - We present an assessment of 200 patellar fractures treated mostly (175) by partial patellectomy. In 23 cases in which the quadriceps mechanism was 75% intact (MRC power approximately 4), the fractures were treated conservatively, with an overall acceptable result. The operative series with an average follow-up of 3 years has shown 80.3% excellent to good results. A classification of fractures of the patella, based on the anatomical fracture line and quadriceps functional loss as recorded in 690 case histories, is suggested. PMID- 1931368 TI - Operative procedure using the improved osteosynthesis technique for intertrochanteric osteotomies. Preliminary report. AB - Employing a simple sawing gauge system in intertrochanteric osteotomies, it is possible to effect "functional pre-bending" of the angled blade plate osteosynthesis in order to achieve better interfragmentary compression and further improve the precision of the standardized AO technique. This new technique may lead to a further reduction of intraoperative and post-operative failures. PMID- 1931366 TI - Overdistraction: a hazard of skull traction in the management of acute injuries of the cervical spine. AB - In acute cervical spine trauma, skull traction is used to reduce a dislocation or fracture dislocation, to immobilize an unstable lesion until definitive treatment (operative or conservative) is possible or, more rarely, as a definitive treatment until healing occurs. This method may be dangerous when an unstable lesion is accidentally overdistracted. A few cases have been reported in the literature, some with neurological complications. We report five cases in which overdistraction was seen. Two hangman's fractures were overdistracted. One of the two patients developed a Cheyne-Stokes breathing pattern during traction which resolved after the weight was reduced. Furthermore, two hyperextension/distraction injuries (C4/5 and C6/7) and one bilateral C5/6 fracture dislocation were overdistracted without neurological deterioration. Occipitocervical dislocations, fractures of the odontoid process, hangman's fractures, hyperextension/distraction injuries and bilateral dislocations or fracture dislocations may present disruption of both the anterior and posterior elements. Therefore, these injuries are specially vulnerable to overdistraction when skull traction is used. To prevent accidental overdistraction during skull traction, we recommend the use of less weight than is generally proposed in the literature. To reduce a dislocation, we start traction weight at 2 kg and slowly increase it under continuous neurological and radiological monitoring until reduction is completed. Traction of 5-7 kg is usually sufficient; however, heavier traction may occasionally be necessary. After reduction is completed, traction is reduced to 2 kg. This weight is sufficient to immobilize a lesion until definitive treatment is possible. Inadvertent rotation may be prevented by placing sandbags on both sides of the head. PMID- 1931369 TI - Clinicoradiological diagnosis of benign osteoblastoma of the spine in children. AB - Three cases of benign osteoblastoma of the spine in children are reported, diagnosed on the basis of clinicoradiological findings and confirmed at surgery and by histopathology. The authors feel that in all cases of painful scoliosis and painful torticollis, a careful search should be made for any suspicious area of sclerosis, especially in the posterior elements of the vertebrae, and all the positive or suspected cases should undergo nuclear bone scanning. All patients whose bone scan is positive should be subjected to computed tomography for differential diagnosis between osteoid osteoma and benign osteoblastoma. PMID- 1931370 TI - Chondrosarcoma of the bones of the hand. Report of two cases. AB - Implantation of chondrosarcoma in the bones of the hands is an infrequent occurrence. We present two cases in which the fifth metacarpal and the proximal phalanx of the index finger, respectively, were affected in two patients aged 47 and 67 years, who, without previous known lesions, came to consultation on the appearance of pain and progressive local growth of tumour. After histological diagnosis we proceeded to disarticulation at the level of the affected bone. We review the literature on the appearance of this type of tumour in the hand. PMID- 1931372 TI - Bleeding in women. PMID- 1931373 TI - Physiology of normal female bleeding. AB - Normal bleeding occurs throughout a woman's life cycle, from puberty to menopause. This bleeding is caused by the interaction of specific hormones. The optimal functioning of these hormones is fundamental to a woman's health. Nurses need to be aware of the physiology related to bleeding throughout a woman's life cycle. PMID- 1931371 TI - Maffucci's syndrome combined with dedifferentiated chondrosarcoma. AB - We report a rare case of Maffucci's syndrome combined with dedifferentiated chondrosarcoma in the right shoulder girdle developing from pre-existing enchondroma. In this case, magnetic resonance imaging was useful in diagnosing dedifferentiated chondrosarcoma before surgery. T2-weighted imaging was used to distinguish between the cartilaginous component and the dedifferentiated one. Histologically, there was enchondroma in the humerus and grade 2 chondrosarcoma in the scapula. Further, the dedifferentiated tumor had three mesenchymal elements: osteosarcoma, malignant fibrous histiocytoma, and fibrosarcoma. This histological heterogenicity may be due to mesodermal dysplasia of Maffucci's syndrome. PMID- 1931374 TI - The elusive premenstrual syndrome. AB - Premenstrual syndrome (PMS) is a condition that is widespread and has been talked about for almost 60 years, yet today there is no consistent method used to diagnose PMS; there is no well-supported etiology; and there is no noninvasive and low-risk proven treatment for the condition. This paper reviews current ideas about diagnosis, etiology, and treatment and makes recommendations for ways a clinician might safely help women with PMS. PMID- 1931375 TI - Menopause: plight or passage? AB - Although the menopause has been discussed in medical, biological, and social science literature, the experience of menopause for women has been shrouded in myths and taboos. Separating myth from reality has been difficult for the American woman, who traditionally has not sought medical advice about the menopause on a routine basis. Health care professionals need to understand the influence of history, culture, taboos, and myths on the symptomatology and interpretation of the menopausal experience. PMID- 1931376 TI - Abnormal bleeding associated with reproductive tract infection. AB - Reproductive tract infection is an often unrecognized, but relatively common, cause of abnormal reproductive tract bleeding. Postcoital bleeding, menorrhagia, metrorrhagia, and oral contraceptive break-through bleeding are potentially infection-related complaints. The microorganisms most often associated with abnormal reproductive tract bleeding include: Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex virus type 2, and microorganisms associated with bacterial vaginosis. The clinical conditions cervicitis, endometritis, and pelvic inflammatory disease and the related microorganisms are discussed, as are strategies for clinical management and counseling. PMID- 1931377 TI - Medical causes of abnormal vaginal bleeding. AB - Abnormal vaginal bleeding, not easily explained by the presence of a gynecologic lesion, infection, or hormonal abnormality, may be caused by systemic medical disease. Evaluation of the clotting system, both platelets and clotting factors, should be done to rule out hematologic disorders that can cause blood loss. Additionally, a detailed history, directed physical examination, and carefully chosen laboratory studies can establish the presence of endocrine disease, renal insufficiency, hepatic abnormalities, and vasculitis. Specific questions about diet and drug use may uncover nutritional deficiencies or adverse drug reactions that produce or contribute to abnormal vaginal blood loss. Evaluations for medical causes of vaginal bleeding may require subspecialty consultation to facilitate timely diagnosis. PMID- 1931378 TI - Evaluation of abnormal genital bleeding. AB - Irregularities of the menstrual cycle, including abnormal genital bleeding, can occur throughout a woman's life cycle. An understanding of the normal menstrual cycle is necessary before evaluation and management of an irregular cycle. Several disorders are defined and described, including appropriate evaluation and management protocols. PMID- 1931379 TI - Hemorrhage and culture: management in the developing world and cultural implications for nursing care. AB - In the industrialized world, technological resources and skilled personnel characterize the response to a hemorrhagic crisis. Such an efficient use of supplied technology stands in stark contrast to the responses toward a similar crisis when encountered in a developing country. In fact, attempting to manage a hemorrhage in a developing country may pose entanglements with economic, political, cultural, environmental, and medical obstacles. The uniqueness of this task and its challenges to the health professional are presented to provide nurses in advanced societies with a basic understanding of principles involved in managing hemorrhage in less-than-ideal circumstances. In addition, cultural care considerations are briefly described as they relate to the nursing role in the developing world. PMID- 1931380 TI - Autologous blood use in obstetrics. AB - The use of autologous blood is of growing concern in the practice of obstetrics. Although prior donation of one's blood for later surgical use and the emergency use of reinfused blood have become established practices, obstetrical use remains controversial because only small groups of women have been studied. This paper gives a brief overview of current issues and use of autologous blood donation in pregnancy and in intraoperative obstetrical procedures. PMID- 1931381 TI - Beta-thalassemia major and sickle cell disease. AB - Beta-thalassemia major and sickle cell disease are genetic disorders of red blood cells, caused by abnormal hemoglobin. These hemoglobinopathies affect males and females equally. Both are chronic disorders requiring lifelong treatment for affected individuals and education and support for them and their families. Special nursing considerations for the care of women facing the unique challenges of these disorders will be discussed. PMID- 1931382 TI - Nongenetic perinatal anemias: conventional, herbal, and homeopathic treatments. AB - Nongenetic maternal anemia long has been recognized as a pregnancy risk factor. A thorough investigation of the patient's laboratory values, diet, medical history, and life-style is basic to successful management. Treatment modalities include conventional, herbal, and homeopathic medicines. Early initiation of a comprehensive anemia program can enhance the quality of life for the mother and improve fetal outcomes. PMID- 1931383 TI - Iron requirements of pregnancy. AB - To maintain the necessary maternal iron stores, the pregnant patient needs to receive iron supplements during the last half of pregnancy. These needs are particularly great during the last trimester, increasing from the usual requirement of 3-4 mg/day to 5-6 mg/day. Dietary and oral supplementation therapies are the most efficient methods of supplementing iron in normal pregnant women and those experiencing iron deficiency. PMID- 1931384 TI - No happy ending: pregnancy loss and bereavement. AB - Bleeding in pregnancy signals not only danger but often failure and loss and the start of bereavement. This chapter identifies types of loss experienced in pregnancy and the bereavement process. In addition, the social aspects of bereavement as they concern marital relationships are identified. The impact of the personal losses of those in the helping profession also are discussed. Working with parents experiencing perinatal death should include interventions involved with physical care, psychological support, and aspects of perinatal death education. Follow-up care is critical to the ongoing assessment and evaluation of parents' progress through the bereavement process. Specific aspects of follow-up care are suggested, including data and information regarding parent support groups. PMID- 1931385 TI - Intrapartum bleeding. AB - Nurses must be alert to a variety of causes for intrapartum bleeding. Some of these are anticipated events, for which the healthy childbearing woman is physiologically prepared. Other causes of blood loss during childbirth are unanticipated, life threatening, and require immediate response from care providers. This paper discusses some of the more frequently mentioned sources of blood loss during the intrapartum period and management of the conditions. PMID- 1931386 TI - Bleeding and the third stage of labor. AB - The third stage of labor often is scarcely considered by parturients and birth attendants although it is thought to be the most dangerous stage of labor because of the risk of significant hemorrhage. Safe clinical management based on respect and understanding of the anatomy and physiology of the third stage of labor may prevent many complications. Management of third stage labor is presented. Uterotonic agents and techniques for control of bleeding are discussed. PMID- 1931387 TI - Use of halogenated anesthesia with maternal hemorrhage. AB - Obstetrical hemorrhage accounts for about 16% of all maternal deaths. The most common cause of hemorrhage is uterine atony. General anesthesia is considered a predisposing cause of uterine atony. This article briefly reviews the hemodynamic changes occurring during pregnancy and uterine atony. Aspects of predisposing factors and management related to the use of drugs and halogenated anesthetics are discussed. PMID- 1931388 TI - Postpartum bleeding. AB - The nurse caring for the postpartum woman must be able to distinguish normal from abnormal blood loss. Characteristics that identify normal lochia are reviewed, as are important nursing assessment parameters. Guidelines for managing impending shock are provided. Problems with blood volume estimations are explored. Information on resumption of menses and patient teaching approaches related to late postpartum hemorrhage are included. PMID- 1931389 TI - Effects of maternal bleeding problems on the fetus and neonate. AB - Maternal bleeding disorders directly affect fetal and neonatal outcome. This article will review how maternal bleeding may cause polycythemia, anemia, or hypovolemic states in the fetus, which will have an impact on the neonatal period. If problems are anticipated, identified, and treated aggressively, outcomes can be improved. PMID- 1931390 TI - Silent myocardial ischaemia in preoperative patients: what does it mean, and what should be done about it? PMID- 1931391 TI - Drug biotransformation by the kidney: how important is it, and how much do we really know? PMID- 1931392 TI - Preoperative silent myocardial ischaemia: incidence and predictors in a general surgical population. AB - We have studied before operation 156 patients aged more than 40 yr presenting for elective vascular or non-vascular surgery, using ambulatory ECG monitoring to detect silent myocardial ischaemia (SMI). The prevalence of SMI was 18.2% in the vascular group (n = 102) and 7.6% in the non-vascular group (n = 54). A history of ischaemic heart disease, or an abnormal ECG suggestive of a previous myocardial infarction, predicted a high risk of SMI (28% compared with 9% in the absence of these variables). However, a significant amount of SMI (36% of the total) occurred in patients without one of the defined risk factors. In addition, 24 of the patients with abdominal aortic disease underwent cardiac gated blood pool (MUGA) scans. Abnormal ventricular wall function was observed in 62.5% of the patients. Twenty-nine percent of the patients studied with MUGA scans had SMI and 21% had ejection fractions less than 40%. A significant association (P less than 0.05) existed between the presence of SMI and a ventricular ejection fraction of less than 40%. PMID- 1931393 TI - Physiological disposition of i.v. morphine in sheep. AB - In a crossover design study we have measured the total body and regional clearances of morphine. Thirteen experiments were performed in four conscious sheep that had been prepared previously with appropriate intravascular cannulae. Morphine (as sulphate pentahydrate) was infused i.v. at 2.5, 5, 10 and 20 mg h-1 to produce constant blood concentrations. Morphine (base) concentrations were measured in blood, urine and tissues with a specific HPLC method. The mean (SEM) total body clearance of morphine was 1.63 (0.21) litre min-1; this comprised 1.01 (0.10) litre min-1 clearance by the liver and 0.55 (0.06) litre min-1 by the kidneys. There was no evidence of dose-dependent clearance or significant extraction of morphine by the lungs, brain, heart, gut or hindquarters at any dose. The kidney clearance of morphine was greater than the 0.21 (0.06) litre min 1 renal clearance determined from the product of the mean total body clearance and the 12.3 (2.4%) of the administered dose recovered as unmetabolized morphine from 48 h urine collection (P less than 0.05). It was concluded that the liver and kidneys account for the majority of morphine clearance, and that the kidneys both excrete and metabolize morphine. PMID- 1931394 TI - Comparison between sevoflurane and halothane for paediatric ambulatory anaesthesia. AB - We have compared the rapidity and quality of recovery after sevoflurane anaesthesia with those after halothane anaesthesia. Thirty unpremedicated paediatric outpatients undergoing pulsed-dye laser therapy for port-wine stains were allocated randomly to receive either halothane or sevoflurane anaesthesia. Each group received 60% nitrous oxide and 1.0-1.5 MAC of volatile agent in oxygen for approximately 40 min. Patients receiving sevoflurane exhibited more rapid emergence and a significantly shorter postoperative recovery time compared with those receiving halothane. No major adverse effects were encountered in each group. These results suggest that sevoflurane anaesthesia is preferable to halothane anaesthesia for paediatric ambulatory patients. PMID- 1931395 TI - Midazolam modifies pancreatic and anterior pituitary hormone secretion during upper abdominal surgery. AB - We have investigated the effects of midazolam on circulating concentrations of pituitary and pancreatic hormones in eight healthy patients during cholecystectomy and compared the changes with those in a control group of eight patients. Anaesthesia was induced either with midazolam 0.42 mg kg-1 i.v. followed by an infusion of midazolam 0.125 mg kg-1 for 1 h, or with a sleep dose of thiopentone. All patients received vecuronium, and the lungs were ventilated with 0.5-1.0% halothane and 70% nitrous oxide in oxygen. The use of midazolam was associated with a significant decrease (P less than 0.05) in secretion of cortisol and insulin during surgery. Serum growth hormone secretion was augmented, but this did not reach statistical significance. There was little difference in the concentrations of circulating metabolites between the two groups, except for a significant decrease in blood glucose (P less than 0.05) in the midazolam group after 60 min. There were no marked differences in cardiovascular variables between the two groups of patients. PMID- 1931396 TI - Clonidine decreases postoperative oxygen consumption in patients recovering from general anaesthesia. AB - Twenty ASA I patients, undergoing thyroid surgery were allocated randomly to receive at the end of surgery either an isotonic saline solution or clonidine 2 micrograms kg-1 i.v. administered over 20 min. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured during recovery in patients breathing spontaneously with a head canopy system. Clonidine was found to attenuate the increase in VO2 and VCO2 associated with recovery from anaesthesia. The effect of clonidine was associated with a reduction in shivering. Sedative and analgesic properties of clonidine may also contribute to the reduction in metabolic demand during recovery from anaesthesia. PMID- 1931397 TI - Effects of adenosine triphosphate on the cardiovascular response to tracheal intubation. AB - Laryngoscopy and tracheal intubation often cause hypertension and tachycardia, which may be exaggerated during rapid-sequence induction of anaesthesia. The efficacy of adenosine triphosphate (ATP) in attenuating this response was studied in patients receiving ATP 0.05 mg kg-1 or 0.1 mg kg-1 simultaneously with the start of laryngoscopy. These data were compared with those for a control group receiving saline. Each group consisted of 10 patients undergoing elective surgery. Anaesthesia was induced with thiopentone 5 mg kg-1 i.v. and tracheal intubation was facilitated with vecuronium 0.2 mg kg-1 i.v. During anaesthesia, ventilation was assisted or controlled with 1% enflurane and 50% nitrous oxide in oxygen. Patients receiving saline showed a significant increase in mean arterial pressure and rate-pressure product associated with tracheal intubation. These increase after tracheal intubation were reduced in ATP-treated patients compared with those of the control group (P less than 0.05). The data suggest that a bolus injection of ATP is a simple, practical and effective method for attenuating the hypertensive response to laryngoscopy and tracheal intubation. PMID- 1931398 TI - Effects of pindolol on the cardiovascular response to tracheal intubation. AB - Laryngoscopy and tracheal intubation often cause hypertension, tachycardia and arrhythmias, which may be exaggerated during rapid-sequence induction of anaesthesia. We have studied the efficacy of pindolol in attenuating the cardiovascular responses to laryngoscopy and intubation in patients receiving pindolol 2 micrograms kg-1 or 4 micrograms kg-1 3 min before induction of anaesthesia in a double-blind design. The data were compared with those in a control group receiving saline. Each group consisted of 10 patients undergoing elective surgery. Anaesthesia was induced with thiopentone 5 mg kg-1 i.v. and tracheal intubation was facilitated with vecuronium 0.2 mg kg-1. Patients receiving saline showed a significant increase in mean arterial pressure and heart rate associated with tracheal intubation. These increases after tracheal intubation were reduced in pindolol 4 micrograms kg-1 treated patients compared with those in the control group (P less than 0.05). Pindolol 2 micrograms kg-1 attenuated tachycardia in response to intubation but did not affect hypertension. These data suggest that a bolus injection of pindolol 4 micrograms kg-1 is a simple, practical and effective method for attenuating cardiovascular responses to laryngoscopy and tracheal intubation. PMID- 1931399 TI - Gastric emptying and small bowel transit in male volunteers after i.m. ketorolac and morphine. AB - Ten male volunteers were studied in a randomized, double-blind crossover trial. Each received ketorolac tromethamine 30 mg and morphine sulphate 10 mg i.m. at an interval of 2 weeks. After a standard radiolabelled meal, gastric emptying half time (GE) and small intestinal transit time (SIT) were measured using a gamma camera. Small intestinal transit time was measured also from end-tidal breath hydrogen (ETH), and overall gastrointestinal motility by time to first flatus (TFF). Mean GE, SIT and TFF were significantly prolonged by morphine compared with ketorolac (P less than 0.03); ETH was prolonged also, but the difference was not significant. There were no significant correlations between SIT, ETH and TFF. Most subjects reported adverse effects after morphine, but only one after ketorolac. PMID- 1931400 TI - Preliminary study to assay plasma amethocaine concentrations after topical application of a new local anaesthetic cream containing amethocaine. AB - Plasma concentrations of amethocaine were measured after topical application of amethocaine cream 2 g (5% w/w) to the dorsum of the right hand of 10 adult volunteers. The cream was applied for 240 min and plasma was assayed for amethocaine and its metabolite p-n-butylaminobenzoic acid at 0, 30, 60, 90, 120 and 240 min in all 10 volunteers, and at 360 min in seven volunteers, by high pressure liquid chromatography. No amethocaine was detected in the plasma of seven volunteers. Plasma concentrations of amethocaine up to 0.20 mg litre-1 were observed in three volunteers. No significant side effects were seen and pain scores on insertion of a 16-gauge cannula were 0 in all subjects. We conclude that the absence of clinical toxicity in the 10 healthy volunteers was a reflection of slow absorption and tissue hydrolysis of amethocaine after topical dermal application. PMID- 1931401 TI - Systemic fentanyl enhances the spread of spinal analgesia produced by lignocaine. AB - Seventy-one patients undergoing transurethral prostatectomy under spinal anaesthesia were allocated randomly to one of four groups; fentanyl-naloxone (F Nal), fentanyl-normal saline (F-NS), normal saline-naloxone (NS-Nal), and normal saline-normal saline (NS-NS) group. Twenty minutes after subarachnoid injection of hyperbaric lignocaine 100 mg, we tested the level of spinal analgesia (pinprick sensation) and administered i.v. either fentanyl 100 micrograms (F-Nal and F-NS groups) or normal saline 2 ml (NS-Nal and NS-NS groups). Ten minutes later, we assessed the new levels of analgesia and administered i.v. either naloxone 0.4 mg (F-Nal and NS-Nal groups) or normal saline 1 ml (F-NS and NS-NS groups). The level of sensory block was reassessed 10 min after the naloxone or normal saline treatment. Ten minutes after i.v. administration of fentanyl or normal saline, the level of analgesia increased in the F-Nal and F-NS groups by 3.98 and 3.78 cm, respectively, and differed significantly compared with the NS Nal and NS-NS groups (both P less than 0.01). Forty minutes after spinal block, the decrease in analgesia in the F-Nal group (3.97 cm) differed significantly from that in the other groups (P less than 0.01). Systemic fentanyl enhanced the spread of analgesia. This enhancement was antagonized by naloxone. PMID- 1931402 TI - Effect of PaCO2 on cerebral blood flow distribution during halothane compared with isoflurane anaesthesia in the rat. AB - In order to examine anaesthetic effects on the distribution of cerebral blood flow (CBF) during normo- and hypocapnia, male adult Sprague-Dawley rats were allocated randomly to four groups in a 2 x 2 factorial design, using PaCO2 value and anaesthetic agent as between-group factors. Animals were anesthetized with either 1.38% isoflurane (inspired) or 1.05% halothane (inspired) and the lungs ventilated mechanically at either normocapnia (PaCO2 5.1-5.6 kPa) or hypocapnia (PaCO2 3.1-3.3 kPa) for 1 h. CBF was measured using 14C-iodoantipyrine autoradiography. Local CBF in selected cortical and subcortical regions of interest and area-weighted mean global CBF were calculated. Data were compared by analysis of variance. Normocapnic (mean (SE] CBF for halothane (n = 6) and isoflurane (n = 7) was 120 (8) ml/100 g min-1 (PaCO2 5.6 (0.49) kPa) and 117 (9) ml/100 g min-1 (PaCO2 5.4 (0.5) kPa), respectively. Hypocapnic CBF for halothane (n = 6) and isoflurane (n = 6) was 82 (7) ml/100 g min-1 (PaCO2 3.3 (0.12) kPa) and 82 (6) ml/100 g min-1 (PaCO2 3.2 (0.12) kPa), respectively. Hypocapnia reduced global CBF for both groups by 30% (P less than 0.001), but there was no difference between anaesthetic agents (P greater than 0.8). Hypocapnia decreased CBF in all local structures examined. Although subcortical structures had similar CBF at both normocapnia and hypocapnia, CBF in three cortical samples was greater (P less than 0.05) in both the normocapnic and hypocapnic halothane groups than the corresponding isoflurane groups. The CBF reactivity to changes in PaCO2 was similar for both agents (approximately 2 ml/100 g min-1 mm Hg). (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931403 TI - The prone position for the surgical patient: a historical review of the principles and hazards. AB - Since the 1940s there has been an increase in the number of patients submitted for surgery of the spinal axis necessitating use of the prone position. Specifically designed operating tables were both rare and expensive, and probably only existed in a few highly specialized centres. Apparatus which could be easily made locally and used in conjunction with normal operating tables has been invented and generally used to good effect. The important historical landmarks in these developments are traced and a review of the methods and hazards is presented. Similar methods evolved almost simultaneously in differing centres. It is recommended that the Tarlov "seated prone" position should be widely used, in view of its physiological advantages and lack of adverse reports. PMID- 1931404 TI - Effectiveness of preoxygenation in morbidly obese patients. AB - The time taken for the oxygen saturation (SpO2) to decrease to 90% after preoxygenation was studied in six morbidly obese patients and six matched controls of normal weight. During apnoea the obese patients maintained Spo2 greater than 90% for 196 (SD 80) s (range 55-208 s), compared with 595 (SD 142) s (range 430-825 s) in the control group (P less than 0.001). One patient in the obese group had desaturation before the onset of complete relaxation and tracheal intubation, without complications. Bedside lung function tests were not significantly different between groups and cannot be used as a predictor of the effectiveness of preoxygenation. PMID- 1931405 TI - Metabolic response to colonic surgery: extradural vs continuous spinal. AB - We have examined the effect of intraoperative and postoperative (4 h) continuous spinal anaesthesia for colonic surgery on the postoperative glucose, lactate and cortisol responses. Twenty-one patients were studied; the first group (control) received general anaesthesia, the second group (extradural) an extradural block (T4-S5) and the third group (spinal) a continuous spinal block (T4-S5). Plasma concentration of glucose increased significantly in the control and extradural groups (P less than 0.05) after surgery, with a small change in the spinal group. Plasma concentration of lactate increased significantly (P less than 0.05) in the control group only. The postoperative increase in plasma concentration of cortisol was similar in both control and extradural groups, and significantly greater than that of the spinal group (P less than 0.05). Thus continuous spinal analgesia attenuated, but did not abolish, the increase in plasma concentration of cortisol associated with colonic surgery. PMID- 1931406 TI - Rapid inhalation induction with isoflurane in humidified carrier gas. AB - This study was designed to determine if rapid inhalation induction of anaesthesia (RII) with 5% isoflurane (4.5 MAC equivalent) in oxygen offers any advantage in terms of complication rate, speed of induction and patient acceptance in comparison with a previously described technique of RII using 2% isoflurane in nitrous oxide and oxygen. Forty ASA I and II unpremedicated patients were allocated randomly to receive RII with either 5% isoflurane in oxygen or 2% isoflurane and nitrous oxide in oxygen. The carrier gas was humidified in order to limit airway irritation associated with the use of isoflurane for inhalation induction. In this study the observed difference in mean induction time (7 s) between the two groups was neither clinically nor statistically significant. The groups were similar also with regard to complication rate and patient acceptance. PMID- 1931407 TI - Unsuspected extradural catheterization in an interscalene block. PMID- 1931408 TI - Superior sagittal sinus thrombosis after internal jugular vein cannulation. AB - A case of cerebral venous sinus thrombosis after central venous cannulation is presented. This occurred after a catheter had been in place for 5 days. The patient presented with thrombosis of the left internal jugular vein 4 days after removal of the catheter. Despite anticoagulation, the patient developed symptoms of increased intracranial pressure. Subsequently, a diagnosis of superior sagittal sinus thrombosis was made. The aetiology, diagnosis and management of this uncommon complication of central venous cannulation are discussed. PMID- 1931410 TI - The pneuPAC hyperbaric variant HB: a ventilator suitable for use within a one-man hyperbaric chamber. AB - We describe the performance of the pneuPAC hyperbaric variant HB, a ventilator designed for use in a one-man hyperbaric chamber. The ventilator delivered minute volumes of 11-23 litre at 1 atm abs to 7.6-16 litre at 2.5 atm abs. The delivered minute volume may be controlled easily from outside the chamber by manipulation of the ventilator rate, 11.5-31 b.p.m. PMID- 1931409 TI - Delayed pneumothorax after subclavian vein catheterization and positive pressure ventilation. AB - Delayed pneumothorax may occur after subclavian vein catheterization and results from slow accumulation of air in the pleural space. Thus initial postinsertion chest x-rays may not detect this complication. The addition of positive pressure ventilation for general anaesthesia may make this complication life threatening. We report three cases and the literature is surveyed. PMID- 1931412 TI - Inhalation induction of anaesthesia with isoflurane in children. PMID- 1931411 TI - Fresh gas utilization of eight circle systems. AB - The fresh gas utilization (FGU) of a semi-closed breathing system is defined as the ratio of the amount of gas reaching the patient's lungs to the total amount of fresh gas flowing into the breathing system. It indicates to what extent a breathing system conserves anaesthetic gases and provides inspired gas concentrations as close as possible to those in the fresh gas, even at low fresh gas flows (FGF). We have measured FGU in eight circle systems used conventionally in Europe: Drager Cicero, Drager Sulla 808V with circle system 8 ISO and ventilator Ventilog, Drager AV1, Ohmeda Modulus II Plus, Gambro Engstrom Elsa, Siemens Servo Ventilator 900 D with circle system 985, Siemens Ventilator 710 and Megamed 700A with circle system 219. The Tests were performed according to the Draft European Standard "Anaesthetic Workstations and Their Modules". None of the systems tested showed the characteristics of an ideal system which would reach 100% FGU with an FGF less than minute volume. At FGF 3 litre min-1, FGU was: Gambro Engstrom Elsa 97.8%, Siemens Servo Ventilator 900 D with circle system 96.1%, Drager Cicero 93.4%, Ohmeda Modulus II Plus 93.1%, Drager 8 ISO 92.3%, Drager AV1 87.6%, Megamed 700A 77.0% and Siemens Ventilator 710 74.1%. PMID- 1931413 TI - Unexpected, difficult laryngoscopy. PMID- 1931414 TI - Atracurium and suxamethonium. PMID- 1931415 TI - Desaturation during total knee replacement. PMID- 1931416 TI - Reporting of deaths. PMID- 1931417 TI - Training in fibreoptic laryngoscopy. PMID- 1931418 TI - Diprivan intensive care sedation in children. PMID- 1931419 TI - Predicting difficult intubation. PMID- 1931420 TI - Pain on i.v. injection. PMID- 1931421 TI - Understanding quality (continuing education credit). PMID- 1931422 TI - Asthma explained (continuing education credit). PMID- 1931423 TI - Comparison of the results of a standardized AIDS prevention program in three geographic locations. AB - A standardized AIDS prevention program, Stop AIDS, was tested with gay and bisexual men in 3 different geographic locations: metropolitan Chicago; Orange County, California; and Phoenix, Arizona, employing a test of AIDS knowledge, attitudes, and behavior. Results indicted that the Chicago participants began with the most knowledge about AIDS but gained least in the workshop, ending lowest, while the Orange County participants started with the least knowledge and gained the most, ending highest. The same change pattern was demonstrated in terms of attitudes. However, all groups started the discussion group with approximately the same risk behavior for HIV transmission, and all groups committed to the same amount of change in risk behavior at workshop termination, demonstrating the independence of behavior change from knowledge and attitude changes. Additionally, all 3 groups had the same 8 of 15 significant correlations of measures with no correlation between knowledge about AIDS, attitudes toward AIDS, and post-workshop intentions regarding risk behavior. These results indicate that Stop AIDS is an effective prevention program in all 3 locations, but that this and other programs should emphasize actual risk-behavior change rather than knowledge increase or healthier attitudes to produce the greatest lethality reduction. PMID- 1931424 TI - Urban African-American and Hispanic adolescents and young adults: who do they talk to about AIDS and condoms? What are they learning? AB - This paper reports on the first qualitative part of a study designed to investigate factors related to the use of condoms among African-American and Hispanic adolescents and young adults in Detroit. This paper describes who young, urban, African-American and Hispanic persons talk to about AIDS and condoms and what they are learning. The paper provides data on attitudes and beliefs about AIDS and condoms that are needed for further research and for prevention programs. PMID- 1931425 TI - Risk assessment for HIV infection: validation study of a computer-assisted preliminary screen. AB - Development has been undertaken for microcomputer software intended to assess individual risk for HIV infection by analyzing personal case histories pertinent to drug abuse, receptive blood transfusion, and sexual behavior. The software performs interactive confidential interviews of individuals desiring expert assistance when deciding whether to commit to an antibody test. In the first phase of a validation study, 87 subjects responded to the computer interview. For each subject, human immunodeficiency virus (HIV) antibody status was on clinical record. This sample included 70 subjects, 29 of whom were HIV seropositive, recruited from the clientele of an AIDS antibody testing and counseling facility. In this phase, the software accurately assessed 28 of 29 seropositives (96.6%) to be at risk for HIV. The second phase was based upon participation of an additional 74 subjects who were undergraduates at the University of Oklahoma. In this presumed low-risk sample, 55 members reported never having previously tested for HIV antibodies. Seven members (12.7%) of the untested group were declared at risk in the course of receiving confidential computer screen advice. Of these 7, there were 3 members (42.9%) who were motivated by the computer to voluntarily seek HIV antibody testing. Of the 7 declared at risk, 2 members (3.9%) were among the 51 seronegative subjects classified as heterosexuals without specific and identified risks. All Phase II subjects seeking follow-up antibody tests were found seronegative. PMID- 1931426 TI - AIDS and women. AB - A number of recent critiques have described the detrimental effects of male centered approaches to medicine, which have resulted in exclusion of female subjects in drug trials and understudy of diseases of women. AIDS represents a prime example of a disease in which a male-centered approach has placed women at a disadvantage for diagnosis, treatment, and care. A CDC Case Definition that does not include gynecologic conditions related to AIDS, research emphasizing women as vectors of transmission to fetus or male partner, and failure to include large numbers of women in AZT and other drug trials are examples of the results of approaches that do not focus on AIDS in women. Including a female-centered perspective in AIDS research will reveal information to help complete the AIDS picture for women, men, and children. PMID- 1931427 TI - Pathways to infection: AIDS vulnerability among the Navajo. AB - Though the development of AIDS cases among Native Americans has paralleled the early stages of the epidemic in the United States, there are socio/cultural distinctions among many U.S. tribes that could lead to transmission differences. Patterns of sexual behavior, IV drug use, suicidality, use of disinhibitors, and the rural-urban migration found among some members of the Navajo Nation are reviewed, along with recommendations for education/prevention program development. The efficacy of anthropological techniques of rapport building and information gathering about sensitive information is also discussed. PMID- 1931429 TI - "Sharing the Challenge" is the theme of World AIDS Day 1991. PMID- 1931428 TI - Confronting the AIDS epidemic among i.v. drug users: does ethnic culture matter? AB - The AIDS education and prevention literature contains numerous calls for the development of culturally relevant efforts to reach members of ethnic minority populations. In the AIDS literature on IV drug users (IVDUs), however, this issue finds less emphasis despite the disproportionate rate of human immunodeficiency virus (HIV) infection in minority IVDUs. The reason appears to be the sense in the drug field that the primary culture of the IVDU is drug culture rather than ethnic culture. This paper explores this issue in light of a review of recent research on IVDUs, ethnicity, and AIDS risk behavior. Specifically, this review covers literature on 6 topics in light of ethnic differences: changing patterns of IV drug use prevalence, AIDS prevalence among IVDUs, needle-related AIDS risk, polydrug use, sexual risk among IVDUs, and the drug subculture. Finding that ethnic culture does matter in infection patterns and risk behavior, this paper examines a typology for the analysis of discontinuities in intercultural communication and presents a framework for comparing alternative models for overcoming cultural barriers to effective AIDS education with IVDUs. PMID- 1931430 TI - Iron metabolism: the low-molecular-mass iron pool. PMID- 1931431 TI - Response to acute nickel toxicity in rats as a function of sex. AB - The effects of different nickel chloride doses upon blood and plasma glucose and essential metal homeostasis were studied in male and female rats. A definite sex dependent response to injections of nickel has been observed for both the increase in plasma and blood glucose levels and the time at which these levels peak. Males showed a fast recovery from the rise in glucose levels and were much less affected by changes in the other parameters studied. In females, an extended rise in glucose levels was observed. All these effects are clearly nickel dose dependent. Plasma, liver and kidney copper levels rose significantly in females while only a small decrease was observed in male kidneys. Zinc levels rose in all organs studied but males recovered to basal levels after the study period, whereas females maintained maximum levels at the end of the same period. An increase in urinary excretion of iron was observed. The present results show that the sex differences to acute nickel toxicity can be a helpful way to study metal interaction and discriminate between specific toxicity due to nickel or that induced by the associated hyperglucagonemia. PMID- 1931432 TI - Novel broad-spectrum metal-based antifungal agents. Correlations amongst the structural and biological properties of copper (II) 2-acetylpyridine N4 dialkylthiosemicarbazones. AB - Copper(II) complexes of the type [Cu(L)X], where L = tridentate anion of 2 acetylpyridine N4-diethyl thiosemicarbazone and X = C1 or Br, were screened against seven fungal strains pathogenic to man viz. Aspergillus niger, Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Tricophyton rubrum, Epidermophyton floccosum and Microsporum canis. The greater growth inhibition exhibited by the bromo complex can be explained on the basis of its lower Cu(II)/Cu(I) redox couple and greater covalent bonding. These compounds represent a novel class of metal-based antifungal agents which provide opportunities for a large number of synthetic variations for modulation of the activities. PMID- 1931433 TI - Influence of salinity on trace metal (Cu, Zn, Ag) accumulation at the molecular, cellular and organism level in the oyster Crassostrea gigas Thunberg. AB - The accumulation and physico-chemical forms of metals were determined by atomic absorption spectrometry in the whole soft tissues of oysters, by histological and microanalytical techniques in tissue sections, by gel permeation chromatography of soft tissue homogenates. Oysters were reared according to four types of experimental conditions: exposed to silver (20 micrograms Ag/l) or unexposed, in sea water (33%) or brackish water (8%). Copper, zinc and silver accumulation in oysters are inversely related to salinity. Amoebocytes, which play a key role in accumulating copper and zinc in natural sea water, are able to sequester an important part of added silver as Ag2S. In brackish water an increase of the number of amoebocytes may be considered as responsible for the enhancement of Cu and Zn concentrations in the whole soft tissues. In such conditions, additional silver is concentrated in these cells rather than in the basement membranes which are target structures for Ag2S accumulation in sea water. If the global fluctuations of metal concentrations in the soft tissue are ascribable mainly to changes at the histological level, the fate of metals in the soluble fraction must not be neglected since the speciation of metals influences their toxicity. The freshening of sea water induced a change in the distribution of cytosolic silver and zinc but in no case were the molecular masses of compounds associated with each metal perfectly identical. From these results, it is concluded that the accumulation of silver by oysters is not mediated by the same mechanisms as those for copper and zinc. PMID- 1931434 TI - Comparative efficacy of chlorophyllin in reducing cytotoxicity of some heavy metals. AB - The potential of chlorophyllin in reducing clastogenicity was studied against two concentrations of each of three potent metallic clastogens (cesium chloride, mercuric chloride and cobalt chloride) in bone marrow cells of mice in vivo. The respective salts and chlorophyllin were administered orally to mice by gavaging in different combinations. Simultaneous administration of chlorophyllin with both concentrations of each salt reduced the clastogenic effects in the order Cs greater than Hg greater than Co. Chlorophyllin could not decrease the clastogenic effects when administered 2 h before the salts. PMID- 1931435 TI - Organ-specific crystalline structures of ferritin cores in beta thalassemia/hemoglobin E. AB - The cores of ferritins isolated from different organs of human subjects with beta thalassemia/hemoglobin E (beta-thal/HbE) disease have different size distributions and crystallinities depending on the source organ. These patients have not been treated by hypertransfusion regimen or iron chelation therapy. beta Thal/HbE spleens and livers yield ferritin cores which are less crystalline than those isolated from normal spleens and livers, reflecting the more rapid deposition of iron in the diseased state. Ferritins isolated from the hearts and pancreases of beta-thal/HbE subjects were found to have larger, more crystalline cores than those from the beta-thal/HbE livers and spleens, possibly as a consequence of the role of the heart and pancreas as long-term iron deposition sites in this iron overload pathology. PMID- 1931436 TI - Relationship between pinocytic rate and uptake of transferrin by suspended rat hepatocytes. AB - The aim of this study was to compare quantitatively the capacity to transcytose (i.e. to uptake and release) transferrin (Tf) with the pinocytic activity of suspended adult rat hepatocytes. An oligodisperse preparation of 131I polyvinylpyrrolidone (PVP; Mr 36,000) was used to measure the inward and outward aspects of the pinocytic process in separate experiments. Cell association of rat 125I-Tf was measured at Tf concentrations approaching physiological, where 59Fe uptake obeyed first-order kinetics. Release studies with both PVP and Tf were carried out under conditions which minimized the probability of de novo endocytosis of a molecule already released. Sets of experimental points representing cell-associated radioactivities were converted into continuous algebraic functions by fitting with two-term (release studies) or three-term (uptake studies) exponential equations. Transport of PVP and Tf through the cells was computed from these equations by deconvolution. This analysis showed that, under the present experimental conditions, the fractional transcytosis rates of Tf and PVP by hepatocytes were in the ratio of 1:0.77. These values imply that, in the physiological range of Tf concentrations, about 75% of the Fe taken up by hepatocytes may be due to a pinocytic mechanism (fluid-phase or mixed). Inclusion of chloroquine (1 mM) in the suspending medium, both in uptake and release experiments, resulted in more PVP and Tf passing through the cells, while Fe uptake was reduced. It is suggested that the base probably exerted its enhancing effect on transcytosis by shunting the subcellular transport of PVP and Tf to the outward leg through a shorter circuit. PMID- 1931437 TI - The role of transferrin and citrate in cellular uptake of aluminium. AB - The ability of human erythroleukaemia K562 cells to take up aluminium from Al transferrin and Al-citrate has been examined. Uptake from Al-transferrin was dose dependent over the range 68-544 ng/ml of aluminium, and increased over a 12-day period. In contrast, uptake from Al-citrate was low even at an aluminium concentration of 6800 ng/ml and did not increase over time. Neither form of aluminium greatly affected cell growth. It is concluded that Al-transferrin, rather than Al-citrate, is the physiologically relevant form of this metal with respect to cellular uptake, but that any metabolic abnormalities induced by aluminium do not affect proliferation of this cell line. PMID- 1931438 TI - Transport and utilization of ferrioxamine-E-bound iron in Erwinia herbicola (Pantoea agglomerans). AB - We have analyzed ferrioxamine-E-mediated iron uptake and metabolization in Erwinia herbicola K4 (Pantoea agglomerans) by means of in vivo Mossbauer spectroscopy and radioactive labeling techniques. A comparison of cell spectra with the spectrum of ferrioxamine clearly demonstrates that ferrioxamine E is not accumulated in the cell, indicating a fast metal transfer. Only two major components of iron metabolism can be detected, a ferric and a ferrous species. At 30 min after uptake, 86% of the internalized metal corresponded to a ferrous ion compound and 14% to a ferric iron species. Metal transfer apparently involves a reductive process. With progressing growth, the oxidized species of the two major proteins becomes dominant. The two iron metabolites closely resemble species previously isolated from Escherichia coli. These components of iron metabolism differ from bacterio-ferritin, cytochromes and most iron-sulfur proteins. All other iron-containing cellular components are at least one order of magnitude lower in concentration. We suggest that the ferrous and ferric iron species correspond to two different oxidation states of a low-molecular mass protein. PMID- 1931439 TI - Heat shock: the role of transient inducible responses in cell damage, transformation, and differentiation. AB - The stress response is ubiquitous among all organisms of the bacterial, plant, and animal kingdoms. A prominent feature of this response is the synthesis of a discrete set of proteins, known as heat shock proteins, that have been shown to be essential in a plethora of protein biosynthetic and processing reactions, including protein folding and oligomerization, translocation, and secretion. During heat shock and other forms of physiological stress, heat shock proteins act as intracellular sentinels to recognize malfolded proteins. The heat shock response is tightly regulated and encompasses selective transcriptional and translational mechanisms that control the preferential synthesis of stress proteins during physiological stress. Deregulation of stress gene expression is associated with various human diseases. It is likely that the balance of interactions between damaged protein molecules and stress proteins has profound effects that impinge on normal cell growth and differentiation. PMID- 1931440 TI - Basic fibroblast growth factor in human melanoma. AB - Basic fibroblast growth factor (bFGF) is a major factor contributing to human melanoma cell growth. bFGF is produced constitutively by cells from each stage of the disease, but not by normal melanocytes, although the latter cells are dependent on the factor for growth in vitro. Two lines of evidence suggest that bFGF functions in an autocrine manner in melanoma: (1) inhibition of bFGF activity by bFGF-specific antibodies or antisense sequences suppresses melanoma cell growth in vitro; and (2) retrovirus-mediated transfer of a bFGF cDNA into normal murine melanocytes renders the recipient cell bFGF-independent. Constitutive production of bFGF is not by itself sufficient for the establishment of the transformed phenotype, however, since bFGF-expressing melanocytes are neither immortalized nor tumorigenic in nude mice. PMID- 1931441 TI - Hormonal carcinogenesis. PMID- 1931442 TI - Monoclonal antibody therapy for cancer. PMID- 1931443 TI - Biological response modifiers. PMID- 1931444 TI - Adoptive cellular therapy. PMID- 1931445 TI - Immunological monitoring and clinical trials of biological response modifiers. PMID- 1931446 TI - Growth and differentiation control. PMID- 1931447 TI - Alkylating agents. PMID- 1931448 TI - Differentiating agents in cancer therapy. PMID- 1931449 TI - Leukemias and myeloma. PMID- 1931450 TI - Lymphomas. PMID- 1931451 TI - Therapy of AIDS and AIDS-related tumors. PMID- 1931452 TI - Anthracyclines. PMID- 1931453 TI - Head and neck cancer. PMID- 1931454 TI - Upper gastrointestinal tumors. PMID- 1931455 TI - Gynecologic malignancies. AB - The combination of cisplatin and cyclophosphamide remains the preferred regimen for the primary treatment of advanced stage epithelial ovarian cancer. Maximal dose intensity, particularly that of cisplatin, is generally accepted as critical for optimal results, but the concept has not yet been rigorously validated by prospective, randomized trials. Since higher doses of cisplatin are associated with renal and neurologic toxicity, the accumulating evidence of equivalent response rates with the less toxic platinum analogue, carboplatin, is encouraging. Salvage chemotherapy remains unsatisfactory, although the remarkable responses observed this year in heavily pre-treated and platinum-resistant patients with the novel new agent taxol is promising. Further trials with this unique drug in combination with other agents in previously untreated patients, as well as in salvage settings, is eagerly anticipated. Although experience with intraperitoneal therapy is rapidly accumulating, the precise role for this route of delivery has yet to be demonstrated in prospective trials. The management of early stage ovarian cancer has become increasingly clarified. Several trials have now demonstrated that a subgroup of patients at low risk for recurrence do well with surgery alone, while a high-risk subgroup clearly benefits from adjuvant therapy. The identification of optimal regimens awaits further trials. In cervical carcinoma, trials utilizing a variety of radiation-sensitizing agents have failed to demonstrate superiority over that of hydroxyurea, which has been shown to improve survival in advanced disease. Preliminary experience with neo adjuvant regimens administered prior to surgery or radiation therapy is promising, but survival advantages utilizing this approach have yet to be demonstrated. In endometrial cancer, cisplatin was shown to achieve response rates similar to those attainable with single agent doxorubicin, and in uterine mixed mesodermal tumors, ifosfamide was found to have significant activity. PMID- 1931456 TI - Breast cancer. AB - Several issues of clinical importance were in the forefront of discussion during 1989. Heated debates continue regarding whether alcohol, oral contraceptives or hormonal replacement therapy modifies a patient's risk for developing breast cancer. It is quite apparent, and rightfully so, that a major impetus in the arena of research in breast cancer seems to be towards cure of the disease. The rationale for offering adjuvant systemic treatment to a larger group of primary breast cancer patients who have a potential for cure certainly seems justifiable. However, one still needs to individualize patients based on their prognosis and objectively weigh the potential benefits and risks of adjuvant therapy in a given clinical situation, especially in patients with less than 1 cm primary tumors and negative axillary nodes as they have been shown to have a 20-year recurrence-free survival of 86%. A better understanding of several molecular and genetic parameters has begun. Further developments in this area may lead to clinically appropriate means of preventing or treating this disease. Metastatic disease continues to remain an incurable entity. Efforts aimed at treating metastatic disease with more 'intensive dose chemotherapy' have not been demonstrated to be beneficial for affected patients. PMID- 1931457 TI - Mitomycin C. PMID- 1931458 TI - Soft tissue and bone sarcomas. PMID- 1931459 TI - Brain tumors. PMID- 1931460 TI - Podophyllotoxin derivatives. PMID- 1931461 TI - Cisplatin. PMID- 1931462 TI - Payments to healthy volunteers--ethical problems. PMID- 1931464 TI - Clinical pharmacology. Roles and responsibilities in academic research. PMID- 1931463 TI - Paracetamol poisoning in children and hepatotoxicity. AB - 1. Paracetamol is one of the most common drugs that children accidentally ingest. Unlike the situation in adults, death and hepatotoxicity in children from paracetamol poisoning are exceedingly uncommon events. A review of the literature has revealed only seven deaths and fourteen cases of hepatotoxicity in children, with most of the cases resulting from chronic poisoning and not acute poisoning. 2. Children may be less prone to paracetamol hepatotoxicity because of developmental differences in the drug's metabolism and its pathways of detoxification. In the therapeutic setting of treatment of fever and pain in children, paracetamol is regarded as a drug with a higher therapeutic index, and as such, there seems to be little concern with strict adherence to dosage regimes. 3. Scrutiny of the above paediatric cases associated with chronic paracetamol poisoning suggests that the margin of safety of frequent therapeutic doses of paracetamol in infants and young children to be a lot lower than previously appreciated. This review highlights the need to re-evaluate the safety of paracetamol in the context of chronic therapy in infants and young children. PMID- 1931465 TI - Clinical pharmacology in the pharmaceutical industry. PMID- 1931466 TI - A new, sensitive graphical method for detecting deviations from the normal distribution of drug responses: the NTV plot. AB - 1. A new graphical method was developed for the detection of deviations from the normal distribution. The approach took advantage of the similarity of graphical features of a graded dose-response relationship and a cumulative normal distribution. 2. The behaviour of the new normal test variable (NTV) plot was evaluated, in comparison with that of the probit plot and probability density functions (the generalization of histograms), for various assumed distributions. These included skewed distributions and composites of normal distributions with a variety of separations, ratios of peak sizes and widths. 3. The NTV approach generally detected deviations from the normal distribution more sensitively than the probit plot. 4. The NTV and probit plots may be able to identify biomadality by complementary approaches. 5. The characteristics of the three graphical representations were illustrated by a simulated sample from a composite of normal distributions and by an example of sparteine metabolism in 142 Cuna Amerindians. PMID- 1931467 TI - A method of studying pharmacokinetics in man at picomolar drug concentrations. AB - 1. We describe a new method that enables the tissue kinetics of picomolar concentrations of drugs to be measured in man. The method is based on the administration of a drug, labelled with a short-lived positron-emitting radioisotope, such as carbon-11 (t1/2 = 20.4 min, beta + = 99.8%) or fluorine-18 (t1/2 = 109.8 min, beta + = 96.9%), which is then detected in vivo by an array of 10 large uncollimated sodium iodide scintillation detectors, arranged as five opposing pairs, with each pair collecting data over one major organ or region of the body. 2. To illustrate the scope of the new method we report the results of administering [O-methyl-11C]-diprenorphine, an established radioligand for central opiate (mu, kappa, and delta) receptors and L-6-[18F]-fluoro-DOPA, a marker for dopaminergic neurons. 3. Only 2-10 muCi (74-370 kBq) of radioactivity are used and, as a consequence of the high specific activities with which carbon 11 and fluorine-18 labelled compounds can be prepared, the method requires less than a nanomole of drug to be administered. In many cases, this amount of drug might be considered low enough to avoid any adverse biological effect. Furthermore repeat studies are possible in many without delivering unacceptable radiation burdens. 4. The high sensitivity realised for both radioactivity and mass suggests a mean for determining the human biodistribution of a new drug at a very early stage in its development. This has potential benefit to drug discovery programmes and to ensuing drug therapies. PMID- 1931468 TI - Disposition and tumour concentrations of platinum in hypoalbuminaemic patients after treatment with cisplatin for cancer of the head and neck. AB - 1 Platinum concentrations in the tumour reached a peak of 3.8 +/- 1.5 micrograms g-1 wet weight tissue at the end of an 8 h intravenous infusion of cisplatin. The tumour concentrations of platinum were higher than the corresponding plasma concentrations (2.5 +/- 0.9 micrograms ml-1) and declined more slowly. 2 Patients with squamous carcinoma of the head and neck had a significantly shorter median survival time if they had low plasma albumin concentrations (less than 40 g l(-1) compared with patients in the normal range, 133 days and 768 days respectively (P less than 0.05) after treatment with cisplatin. 3 No changes in the pharmacokinetics of platinum were detected to account for this poor response of hypoalbuminaemic patients, but plasma albumin concentration was found to be negatively correlated with the first order elimination rate constant. 4 The cumulative urinary excretion of platinum in the first 24 h was not altered by lowered plasma albumin. 5 The concentration of platinum in the tumour did not correlate with the survival time of the patient, but was found to be correlated with the volume of distribution in the post-distributive phase. PMID- 1931469 TI - Prolonged effect of CGRP in Raynaud's patients: a double-blind randomised comparison with prostacyclin. AB - 1. Calcitonin gene related peptide (CGRP) is a potent endogenous vasodilator to which we have previously demonstrated a specific hypersensitivity in skin blood flow in the hands in patients with Raynaud's disease. 2. We have now investigated whether long infusion of CGRP can relieve symptoms of patients with Raynaud's disease using prostacyclin as a control. 3. Six patients were randomised to receive intravenous infusion of either human alpha-CGRP on one occasion, or prostacyclin (PGI2) on another occasion in a double-blind and cross-over design. The dose of each agent was initially titrated up to 8 ng kg-1 min-1 or to a maximum increase in heart rate of 25 beats min-1. 4. In addition to blood pressure, heart rate and skin blood flow measurements, infrared thermography and cold stress challenge was performed before, immediately after infusion and at 3 and 14 days post-infusion. 5. CGRP caused an increase in hand skin blood flow throughout its infusion, whilst PGI2 caused only a short lived increase. The thermographic results showed significant improvement in hand rewarming 3 days after CGRP but not after PGI2. 6. We conclude that 3 h infusion of CGRP was better tolerated than PGI2 and caused objective improvement up to 3 days. CGRP may be an alternative to PGI2 in some patients. PMID- 1931470 TI - The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations. AB - 1. The effect of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations was investigated in healthy volunteers in two separate studies, using a randomized cross-over design with two phases. 2. A single dose of magnesium hydroxide (850 mg) or water only (150 ml) was given immediately after the ingestion of a micronised (1.75 mg, seven subjects) or a non-micronised (2.5 mg, six subjects) preparation of glibenclamide. Plasma concentrations of glibenclamide, insulin and glucose were measured. 3. Magnesium hydroxide accelerated (P less than 0.05) the absorption of glibenclamide from the micronised preparation to a small extent but the extent of absorption and the insulin and glucose responses were unaltered. 4. Coadministration of magnesium hydroxide with the non-micronised glibenclamide preparation increased the area under the plasma glibenclamide concentration-time curve from 0 to 3 h, five-fold (P less than 0.05), the total area three-fold (P less than 0.05) and the peak drug concentration three-fold (P less than 0.05). The incremental insulin area from 0 to 3 h was increased 35-fold (P less than 0.05) and the maximum insulin response 10-fold (P less than 0.05) by magnesium hydroxide. 5. Concomitant ingestion of magnesium hydroxide and non-micronised glibenclamide may greatly enhance the absorption and efficacy of glibenclamide. The absorption of micronised glibenclamide appears to be only slightly influenced by magnesium hydroxide. PMID- 1931471 TI - Metabolism of the aldose reductase inhibitor ALO1567 in man. AB - 1. The metabolism of the aldose reductase inhibitor, ALO1567, was studied in man. The major biotransformation pathway was aromatic hydroxylation followed by glucuronide conjugation. 2. Hydroxylation occurred at several positions on the fluorene ring. The major metabolite was identified as the 7-hydroxy analogue of ALO1567 and three minor metabolites were characterized as positional isomers of the 7-hydroxy metabolite. 3. Oxidative defluorination and metabolism on the hydantoin ring were also indicated as minor pathways. 4. The capacity of normal subjects to oxidize ALO1567 was indicated by the urinary ratio of the parent drug to the 7-hydroxy metabolite after daily oral administration of 100 mg and 200 mg of ALO1567. Most subjects having higher ALO1567 plasma concentrations showed higher ratios. PMID- 1931472 TI - Subcutaneous apomorphine increases regional cerebral blood flow in parkinsonian patients via peripheral mechanisms. AB - 1. We have measured regional cerebral blood flow (rCBF) and motor function before and after the subcutaneous (s.c.) injection of apomorphine in parkinsonian patients deprived of their usual treatment for at least 48 h. 2. Nineteen patients, pretreated with domperidone (20 mg three times daily for 48 h), received a mean dose of 5.8 mg s.c. apomorphine. All patients switched 'on'. The mean motor score was significantly improved (-65%, P less than 0.01) but no significant change in rCBF was observed. 3. Seven other patients, not pretreated with domperidone, received a lower dose (0.3 mg) of s.c. apomorphine. No change in motor score was observed while the mean rCBF significantly increased (+12%, P less than 0.05). 4. We conclude that s.c. apomorphine increases rCBF in parkinsonian patients. This effect is independent of the central therapeutic effects of the drug. It is mediated by the stimulation of dopaminergic receptors of the cerebral vessels. These receptors are located outside the cerebral blood brain barrier and can be considered as 'peripheral' ones. PMID- 1931473 TI - Polymorphisms in oxidative drug metabolism: relationship to food preference. AB - To determine whether a correlation exists between polymorphisms of oxidative drug metabolism and dietary preference, 29 poor metabolizers of dextromethorphan, 18 poor metabolizers of mephenytoin and 134 extensive metabolizers of both drugs were screened for their preferences for various food items. Poor metabolizers of dextromethorphan showed a diminished stated preference for cauliflower and coconut, and poor metabolizers of mephenytoin showed a diminished stated preference for spinach and cabbage. PMID- 1931474 TI - 1-Methylxanthine derived from theophylline as an in vivo biochemical probe of allopurinol effect. AB - The urinary 1-methyluric acid (1MU) to 1-methylxanthine (1MX) ratio has been assessed as a biochemical index of oxipurinol effect in vivo in man. Dosing with theophylline was used to produce 1MX as an intermediate metabolite in six healthy volunteers. A sigmoid Emax model was fitted to the data and gave a mean plasma oxipurinol IC50 of 3.0 +/- 1.1 mg l-1, a mean exponent n of 3.4 +/- 2.1 and a mean IC90 of 8.5 +/- 5.9 mg l-1. There was marked interindividual variability in the steepness of the plasma oxipurinol concentration response relationship, and in the plasma oxipurinol IC90 values. The study has confirmed the feasibility of using single doses of allopurinol to construct individual plasma oxipurinol concentration-response curves. PMID- 1931475 TI - Pharmacokinetics of the anti-inflammatory drug ximoprofen in healthy young and elderly subjects: comparison with elderly rheumatic patients. AB - The pharmacokinetics of ximoprofen were studied in young and elderly subjects after single and repeated doses up to 30 mg. In healthy elderly subjects (30 mg dose), a mean peak plasma drug concentration of 1.78 micrograms ml-1 +/- 0.83 s.d. occurred at a mean time of 1.95 h +/- 1.40 s.d. and, thereafter, concentrations declined monoexponentially with a mean half-life of 3.8 h +/- 1.4 s.d. Comparison of these data with those from younger healthy subjects showed that peak drug concentrations, areas under the curve and half-lives were about two-fold greater in the elderly, these differences probably reflecting a lower systemic drug clearance. Similar results were obtained on comparing data from young healthy subjects and elderly rheumatic patients receiving single and repeated doses of ximoprofen (15 mg twice daily). In patients, the half-life of ximoprofen was 2.5 h +/- 0.7 s.d. Within either group, pharmacokinetic parameters after single or repeated doses were similar: ximoprofen did not accumulate in the plasma of the young or elderly. PMID- 1931476 TI - The relative bioavailability of diclofenac with respect to time of administration. AB - The pharmacokinetics of diclofenac after a single oral dose (50 mg) were studied in 10 healthy adults on two occasions separated by 2 weeks, once in the morning (dose administered at 07.00 h) and once in the evening (dose at 19.00 h). Peak serum drug concentrations as well as the area under the drug concentration-time curve were significantly less during the night compared with the day (Cmax: 1886 +/- s.d 901 vs 2791 +/- 1565 ng ml-1 and AUC: 2807 +/- 1376 vs 3681 +/- 1986 ng ml-1 h). However, the time to reach peak concentration (tmax) and the half-life of diclofenac (t1/2) were not significantly different on the two occasions. We suggest that the extent of diclofenac absorption is slightly lower following administration in the evening compared with administration in the morning. PMID- 1931477 TI - The disposition of bupivacaine following a 72 h interpleural infusion in cholecystectomy patients. AB - The disposition of bupivacaine and degree of analgesia following a 72 h interpleural infusion was investigated in 12 adult patients undergoing elective cholecystectomy. The infusion regimen of an initial interpleural bolus dose of 20 ml of 0.5% bupivacaine HCl with adrenaline (1:200,000) followed by continuous infusion at a rate of 8 ml h-1 of 0.25% plain bupivacaine HCl was designed to achieve continuous post-operative pain relief for 72 h. In practice an additional bolus dose (identical to the first) administered 5 h after infusion commencement was required to achieve adequate pain relief on the first postoperative day. The mean measured steady-state plasma bupivacaine concentration was 2.1 mg l-1 (s.d. +/- 0.54, range 1.3-3.2 mg l-1). Disposition parameters for bupivacaine measured for the infusion were calculated by non-compartmental methods and compared with previous values obtained after single and multiple interpleural bolus dose administration. No statistically significant differences were noted and, in particular, the systemic clearance of bupivacaine (mean 10.2 l h-1 s.d +/- 3.0; range 6.3-16.0 1 h-1) remained unchanged following the long-term interpleural infusion. Analgesia was deemed satisfactory throughout the entire post-operative period. PMID- 1931478 TI - Salivatory effects induced by selective and non-selective cholinolytics in the chronically denervated human parotid gland. PMID- 1931479 TI - Antimuscarinic and anticholinesterase activity of cimetidine and ranitidine: clinically significant? PMID- 1931480 TI - Centrosome signalling at mitosis. PMID- 1931481 TI - Stimulated phosphatidylcholine hydrolysis as a signal transduction pathway in mitogenesis. PMID- 1931482 TI - Protein kinase C-dependent activation of a myelin basic protein kinase by gastrin releasing peptide in Swiss 3T3 fibroblasts. AB - Addition of gastrin releasing peptide to serum-starved Swiss 3T3 mouse fibroblasts results in a transient appearance of a myelin basic protein-kinase activity in cytosolic extracts. Increased kinase activity is also observed upon stimulation of cells with bradykinin, epidermal growth factor or 4 beta-phorbol dibutyrate. Chromatographic analysis of the cytosolic extracts show that both gastrin-releasing peptide and 4 beta-phorbol dibutyrate induce the appearance of a kinase activity similar to that induced by epidermal growth factor. The response to gastrin-releasing peptide is abolished by down-regulation of protein kinase C and attenuated by acute inhibition of protein kinase C using staurosporine. The effect of epidermal growth factor was also suppressed under these conditions, albeit to a lesser extent. The results indicate (1) that activation of myelin basic protein kinase(s) may be common to different growth factors, and (2) that protein kinase C may participate in this response, at least in the case of gastrin-releasing peptide. PMID- 1931483 TI - A quantitative analysis of the role of K+ channels in mitogenesis of neuroblastoma cells. AB - The role of K+ channels in mitogenesis was studied on mouse neuroblastoma cells by analysing the effects of various chemical agents on the whole-cell K+ current and the cell proliferation. The outward current recorded during depolarizations on undifferentiated cells was made up of a small and slow inactivating K+ current. Foetal calf serum, which is mitogen for neuroblastoma cells, shifted in opposite directions by 7-10 mV peak activation and steady-state inactivation voltage curves of the K+ current. The resulting effect was an increase in K+ conductance. The effect on the resting K+ flux of the classical K+ channel blockers tetraethylammonium, 4-aminopyridine and capsaicin, the anticancer agent tamoxifen, the heat inactivated serum and the increase in external K+ concentration were estimated from their effects on the K+ current. The cell proliferation was determined under the same conditions. The results indicate that cell proliferation is correlated to the resulting K+ flux. It is supposed that mitogenesis is controlled by the intracellular Na+ concentration which, via a cell volume regulation, is a function of the K+ flux. A quantitative model is developed on the basis of these hypotheses. PMID- 1931484 TI - The transduction signalling protein Go during embryonic development of Drosophila melanogaster. AB - G proteins are heterotrimeric proteins that play a key role in signalling transduction conveying signals from cell surface receptors to intracellular effector proteins. In particulate preparations from Drosophila melanogaster embryos, only one substrate of 39,000-40,000 molecular weight could be ADP ribosylated with pertussis toxin. This substrate reacted in immunoblotting and immunoprecipitation experiments with a polyclonal antibody directed against the carboxy-terminal sequence of the alpha subunit of the mammalian Go protein. The Drosophila Go alpha protein was present at all stages of embryonic development; however, its expression markedly increased after 10 h embryogenesis, a period of time during which there is an active development of axonal tracts. Immunolocalization on whole mount embryos has indicated that this protein is principally localized in the CNS and is mainly restricted to the neuropil without any labelling of the cell bodies. In contrast, all the axon tracts of the CNS appeared to be highly labelled. The distribution of the Go alpha protein was also examined in several neurogenic mutants. The Go alpha protein expression was not altered in any of them but the pattern of labelling was disorganized as was the neuronal network. These results suggest a possible role for the Go protein during axonogenesis. PMID- 1931485 TI - How to assess acute cerebral ischemia. AB - There are different approaches to the assessment of acute stroke. Its causes, its severity, and/or its final prognosis may be investigated. The traditional approach is anatomoclinical. It is basically limited to finding out if the lesion is a hemorrhage or an ischemia, and its location. This approach is derived from and supported by the fact that acute stroke is still without a valid therapy. In our opinion, not stroke but individual patients presenting with stroke should be treated. The pathophysiology of the individual stroke should be investigated by means of new techniques: magnetic resonance, emission tomography, and transcranial Doppler. These new techniques will be important in the future, making it possible to create effective therapeutic strategies, designed for treating a particular subgroup of patients, as in the case of fibrinolytic agents. The main aspects of these new techniques for evaluating acute ischemic stroke have been reviewed in this article. PMID- 1931486 TI - The excitotoxin hypothesis in relation to cerebral ischemia. AB - The distribution of brain cell injury following transient ischemia is remarkable because only certain neurons in distinct brain regions are destroyed (selective neuronal death). Because excitatory neurotransmitters (glutamate and aspartate) cause a similar pattern of selective neuronal death, it seemed only natural to associate these effects with the trauma of ischemia. This led to the formulation of the excitotoxin hypothesis, which explains selective neuronal death as a result of excessive interstitial concentration increases of excitatory amino acids during ischemia, resulting in the opening of receptor-coupled ionophores, of which calcium channels are of particular interest. A large influx of calcium associated with impaired intracellular calcium sequestration mechanisms due to energy failure activates a host of catabolic enzymes that ultimately will cause neuronal death. The purpose of this work was (a) to measure extracellular glutamate concentration increases during ischemia in a selective vulnerable brain region (rat CA1 hippocampus), (b) to evaluate the toxicity of such a concentration increase, and (c) to investigate the relationship between ischemia induced glutamate accumulation and changes of calcium homeostasis. The execution of these experiments required a method that was able to sample excitatory amino acids in the brain extracellular space for subsequent analysis by high performance liquid chromatography (HPLC). The choice of the microdialysis technique proved most satisfactory and further mathematical analysis made it possible to transform dialysate glutamate concentrations to extracellular concentrations. The study demonstrated that extracellular glutamate in CA1 reached toxic concentrations during ischemia. There appeared to be a clear correlation between ischemia-induced glutamate accumulation and the decrease in extracellular calcium since both changes were prevented in the denervated CA1 (the destruction of glutamatergic innervation from CA3 protects CA1 pyramidal neurons from ischemic damage). By contrast, blockade of N-methyl-D-aspartate (NMDA) receptors with the glutamate antagonist APV was only partially effective in preventing the ischemia-induced calcium changes in CA1. Taken together, these results support the excitotoxin hypothesis but question the rational of treating neuronal injury caused by transient global ischemia exclusively with NMDA antagonists. PMID- 1931487 TI - [Sutures in surgery and the prospects]. PMID- 1931488 TI - [Esophageal achalasia in children]. AB - The achalasia is an uncommon pathology in childhood but the disturbances in growth, development and the severity of pulmonary symptoms are more severe than adults. In a period of twenty five years we have diagnosed three children of sixteen months, 4,5 and twelve years of achalasia and treating them with a modified Heller procedure as primary therapy adding anti-reflux procedure in the youngest. Literature review indicates excellent results following modified Heller's operation in more than 85 per 100 of cases. When an anti-reflux procedure is not performed the incidence of gastro-oesophageal reflux in childhood is 20 per 100. PMID- 1931489 TI - [An experimental models in the evaluation of the effect of the amniotic fluid]. AB - Fetal life develops in a fluid environment. Amniotic fluid is not inert. It contains proteins, hormones, fetal urine and electrolytes, known to interact with a variety of fetal processes such as wound healing, intestinal growth, etc. Interest in its study has been increasing recently. In order to determine the effect of amniotic fluid, intra-amniotic and extra-amniotic fetuses should be compared. We describe a model that allows isolation of a fetal portion from amniotic fluid. Sixty 23-day pregnant rabbits were operated on. Surgery was performed in two fetuses of each mother. One fetus was replaced into the amniotic sac; the other was sutured along its waist to the histerotomy orifice, leaving the caudal half of the fetus in an extra-amniotic position. The mothers continued their pregnancy and were sacrificed on day 30. Maternal survivance rate was 82 per 100. Twelve intra-amniotic fetuses (FIA) and nine extra-amniotic fetuses (FEA) were obtained, as well as 16 nonoperated littermates that served as controls. The average weight of FIA fetuses was 31 g, FEA fetuses weighed 37 g and controls 36 g. The difference was not statistically significant between any of the groups. This model allows the study of a variety of fetal conditions in the absence of amniotic fluid. The survivance rate of this technique of extrauterine fixation has been 75 per 100. PMID- 1931490 TI - [Warren's shunt in the treatment of portal hypertension in children]. AB - Portal hypertension (PH) is often of extrahepatic origin in children. Several approaches have been proposed for its management: Observation, endosclerosis, devascularization and portosystemic shunting. Only the latter has an adequate haemodynamic rationale but the surgical risks, the fear of later portal deprivation encephalopathy and the difficulties of performing technically satisfactory anastomosis have discouraged many surgeons. Warren's distal spleno renal shunt, selectively decompress esophageal varices and cures hypersplenism while sparing the spleen and providing a high flow anastomosis. We have used this operation in three patients with extrahepatic PH. All patients ceased bleeding and had their spleen size reduced with normal function. PMID- 1931491 TI - [Participation of the colon in the compensatory process after massive intestinal resection. An experimental study in rats]. AB - The colon participation in the adaptation process after massive intestinal resection (R.I.M.) has been rarely studied. This is an experimental study in rats to know the morphological modifications to the colon after R.I.M. of small bowel. A total of 90 Wistar rats weighing 200-250 grams were used, in two groups. Twenty animals constituted group I (control) and 70 were submitted to resection of 85-90 per 100 of the small bowel (group II, R.I.M.). Radiologic and weights controls has been performed. To end of study (four months),a the animals were sacrificed to obtain histologic samples of the large bowel for structural and morphometric studies. The results of this study to confirm the colon participation in the compensatory adaptation process after R.I.M. of small bowel. PMID- 1931492 TI - [Our experience with aspiration of ectopic ureteroceles]. AB - Since 1986 we have performed suction of the ectopic ureteroceles in seven cases. In four of these cases the obstruction caused by the ureteroceles affected the upper hemi-kidney. In the remaining three cases both hemi-kidneys of the same side were affected. One child suffered failure of both hemi-kidneys. All the ureteroceles corresponded to the upper hemi-kidney and were associated with ipsilateral duplicity. In four of the cases the treatment applied was the heminephrectomy of the upper hemi-kidney and the suction of the ureterocele. In one case, we did a nephrectomy and suction of the ureterocele. In the remaining two cases the suction of the ureterocele was done, as well as the ureteropyelostomy, since it was necessary to use the upper hemi-kidney in the renal TC99m dimercaptosuccinic acid scan-DMSA. In five of the children there was a collapse of the ureterocele giving good results in both kidneys. In two of the children there was no collapse, which provoked the need for removal of the ureterocele. In one of these two cases, the renal dilatation persisted later. In the last case it was necessary to perform nephrectomy due to the absence of recuperation of the renal function. Three of the children had associated reflux which disappeared in one of them, after the suction of the ureterocele. Vesical surgery might be avoided by means of the ureterocele's suction technique in 60 per 100 of the cases. However, it is essential to pursue the child's progress once every six months, in order to detect possible failures of ureterocele collapse. PMID- 1931493 TI - [Diagnostic significance of systematic neonatal urinary echography. Therapeutic implications]. AB - A total of 9,959 ultrasonography studies of the upper excretory urinary system during the first three days of life of all the children born in this centre were carried out over a period of three years. Sonographic abnormalities were found in 125 patients (1.26 per 100) consisting of: Prominent pelvis in 35, pyelic ectasia in 45, hydronephrosis in 16, ureterohydronephrosis in seven, renal agenesis in 14, multicystic kidney in two, renal ectopia en two, other anomalies in four. There had been prenatal sonographic diagnosis of the urinary tract abnormality in 24 patients, all with pyelic ectasia or hydronephrosis. The sonography of the patients with prominent pelvis normalized before three months of age. Intravenous urography was performed on most of the remaining 90 patients, confirming the diagnosis in the greater part, and serial voiding cystourethrography which detected vesicoureteric reflux in 21 of 77 patients. The definitive diagnosis was arrived at in all patients after carrying out the sonography and the uroradiological test. This made prophylactic antibiotic treatment possible in many of the cases and surgical correction of the anomaly in 30, performing pyeloureteroplasty in 11, neo-ureterocystostomy in 10, nephrectomy in five, heminephroureterectomy in three and derivation to the skin in one. Twenty of these patients were operated before three months of age. The number of uropathies operated at early ages at this centre has risen remarkably since introduction of systematic neonatal urinary sonography. PMID- 1931494 TI - [Prominent ears. Correction using a modified Chongchet technique]. AB - The authors describe their experience with the correction of prominent ears using a modified Chongchet technique. This method is based on the investigations of GIBSON and DAVIS (1958), who showed the tendency of cartilage to warp when one surface is cut. The prominent ear is folded back to produce the desired antihelix fold, which is outlined with methylene blue. An elliptical piece of retroauricular skin is excised. An incision is made through the whole thickness of the cartilage, following the posterior marked linea of the new antihelical fold, from the superior crus to the tail of antihelix. The anterior surface of the cartilage is dissected from the skin. A series of parallel incisions are made through the taut outer layer of the future fold. The tension on that side is released, and therefore it will bend towards the opposite side. The antihelical fold is corrected. This method was used in 192 patients with prominent ears. The results were satisfactory, with a normal-looking fold of antihelix. No recurrence of the deformity was seen. PMID- 1931495 TI - [Results of the treatment of Hirschsprung's disease using Duhamel technique and mechanical sutures]. AB - The original Duhamel procedure for the treatment of Hirschsprung's disease (HD) has undergone several important modifications over the years. The use of mechanical suture in recent years has added significant advantages to this surgical procedure. Sixteen patients with HD were operated on according to this surgical technique, from 1985 to 1990. We analyse clinical, radiological and surgical aspects. We concentrate on early and late postoperative complications and the results achieved after a maximum follow-up of 4.5 years. PMID- 1931496 TI - [Congenital esophageal stenosis associated with corneosclera]. AB - One case of congenital esophageal stenosis due to tracheobronchial remnants and associated with microphthalmos and corneosclera is reported. Diagnostic and therapeutic methods employed are discussed. PMID- 1931497 TI - [Acute acalculous cholecystitis secondary to immersion asphyxia. Implications in organ donation]. AB - A case of acute acalculous cholecystitis in a two year-old girl that undergone drowning in sweet water is reported. Cerebral death was diagnosed and the organs donation was authorized. A biliary peritonitis secondary to gallbladder perforation was met during organs extraction. The liver was rejected. PMID- 1931498 TI - [Congenital sternal cleft]. AB - We report two congenital sternal cleft cases, Ravitch type 1, and treated in our hospital during a period of five teen years. This is a rare malformation and the experience is poor. Surgical primary close was realized into the first month of life with satisfactory evolution. PMID- 1931499 TI - Iodinated radiographic contrast media: comparison of low-osmolar with conventional ionic agents [corrected]. AB - A large number of reports on radiographic contrast media have appeared over the past year. The majority of these compared various properties of the new, nonionic low-osmolar agents with those of conventional ionic contrast media, including types and rates of adverse reactions, nephrotoxicity, anticoagulant effects, degree of subcutaneous injury resulting from extravasation, and gastrointestinal tolerance. In this review, recent developments in each of these areas are discussed. Although, in general, the newer agents are safer and better tolerated than ionic contrast media, their greatly increased cost prevents them from completely replacing these media. In this time of increasingly cost-conscious health care, even expert opinion concerning indications for nonionic low-osmolar contrast media use (also summarized here) is widely divided. PMID- 1931500 TI - Imaging of renal cystic diseases. AB - The improved understanding of hereditary cystic diseases is changing the nomenclature used to describe these diseases. Detailed family studies of the inheritance of these conditions become possible as the genes involved, or their DNA markers, are identified. At the same time, ultrasonography allows cystic disease to be detected very early in life in some patients. The new information necessitates changes in the terminology, which was based previously on the patient's age at clinical presentation. Thus, because ultrasonography now sometimes identifies the cysts of adult polycystic kidney disease in utero or in neonates, the term autosomal dominant polycystic kidney disease is now more appropriate. Similarly, the term autosomal recessive polycystic kidney disease is replacing infantile polycystic kidney disease. Despite the success of ultrasonography in identifying the cysts of these and other inherited conditions very early, it is important to appreciate that precise definition of the type and heredity of the condition concerned requires detailed pathologic and genetic studies. The other renal cystic disease receiving considerable attention in the recent literature is acquired cystic disease, about which more data are accumulating. With increasing numbers of patients on long-term dialysis, the condition and its complications, especially renal adenocarcinoma but also hemorrhage, continue to cause concern. The evidence for an increased incidence of renal cell carcinoma has strengthened over recent years, and the debate on the need for CT screening of patients on long-term dialysis continues. PMID- 1931501 TI - Imaging of solid renal masses. AB - Detection of renal cell carcinoma is still a major task for the radiologist. Ultrasonography has replaced excretory urography as the most cost-effective means of detecting early renal cell carcinoma. Detection of small tumors confined to the renal parenchyma has made partial nephrectomy a safe therapeutic alternative, but a longer life expectancy has not been proved. Doppler ultrasonography and MR imaging are used to help distinguish between benign and malignant renal tumors with initial equivocal results. However, accurate diagnostic criteria for CT have been developed and CT remains the standard diagnostic method for characterizing and staging renal tumors. MR imaging has one major advantage: it depicts the degree of tumor involvement of the renal vein and inferior vena cava. Percutaneous fine-needle aspiration biopsy is still important for discriminating between benign and malignant tumors as well as enlarged lymph nodes. PMID- 1931502 TI - Doppler sonography in renal diseases. AB - Using Doppler sonography, the circulation of the kidney can now be studied in the living person in various physiologic or pathologic situations. Our understanding of renal hemodynamics, gleaned from experimental animal models as well as human studies, is being enhanced by Doppler examination and the clinical uses are expanding. Some early concepts, sometimes hastily postulated, are being questioned. The highlights of ongoing debates and the results of animal studies that further our understanding of Doppler examinations in patients are the subject of this review. PMID- 1931503 TI - Imaging of adrenal metastases. AB - This paper discusses the application of CT, MR imaging, and 131I-6 beta iodomethyl-19-norcholesterol scintigraphy in establishing the nature of incidentally discovered adrenal masses. It is concluded that CT and MR imaging can permit confident differentiation between nonhyperfunctioning adenomas and metastases in cases of incidentalomas that meet all the criteria of a nonhyperfunctioning adenoma. In cancer patients, fine-needle aspiration biopsy of lesions is, in general, essential because a definitive diagnosis of metastatic disease is crucial to disease management. MR imaging and norcholesterol scintigraphy are useful if a relative contraindication for fine-needle biopsy exists or when biopsy results are inconclusive in patients with a presumably benign lesion. PMID- 1931504 TI - Evaluating the role of transrectal ultrasonography and magnetic resonance imaging in prostate carcinoma. AB - A review of the recent literature on the performance of transrectal ultrasonography and MR imaging in the evaluation of prostate carcinoma demonstrates the typical evolutionary cycle inherent in any technology assessment: increasingly improved methodology has resulted in the tempering of initial enthusiastic reports by more sober observations and realistic expectations. This inevitable and predictable evolution should not be interpreted as a criticism of earlier work; designing and implementing a rigorous study of new and rapidly changing technology is a challenging endeavor. Nevertheless, the most current work has greatly helped to provide a more balanced and convincing perspective that is more useful to the practicing radiologist. PMID- 1931505 TI - Testicular imaging. AB - Clinicians have relied on radionuclide scanning for evaluating acute scrotal pain and on ultrasonography for chronic scrotal pain and anatomic lesions (testicular and paratesticular structures). This review reinforces the utility of these established imaging techniques and also introduces color Doppler ultrasonography as an integral component in the advancement of testicular imaging, particularly in effective and timely diagnosis of spermatic cord torsion. The expanding capability of MR imaging for scrotal disorders is presented. PMID- 1931506 TI - Imaging of musculoskeletal trauma. AB - Many significant papers in the current literature on musculoskeletal trauma deal with new advances in MR imaging. The increasing role of MR imaging in the evaluation of traumatic lesions of the knee explains the number of papers dealing with the differentiation of true traumatic lesions from normal variants or clinically insignificant changes. Other contributions on musculoskeletal trauma deal with more conventional imaging techniques, such as arthrography, plain films, and even complex tomography. PMID- 1931507 TI - Imaging of bone and joint infections. AB - In recent years, world interest in bone infection has centered on investigating the potential of the newer imaging methods for detecting early osteomyelitis and on their sensitivity and specificity in evaluating both the acute disease and recurrence of chronic disease and the development of infection in prostheses. No revolutionary new techniques were forthcoming since the advent of MR imaging, and the past 12 months have seen a decline in new analyses, presumably because most researchers have now made up their minds about the relative imaging modalities. Interest lately has been mainly in the imaging of chronic (granulomatous) disease and patterns in children and in drug abuse patients. Because of the importance of differentiating neuropathy from infection in the diabetic foot, research is also active in this field, particularly in relation to dynamic scintigraphy. Interesting observations continue to emerge on infection resulting from the depressing spread of drug abuse and immunosuppression. PMID- 1931508 TI - Imaging of disorders of the spine. AB - Although many papers were published during the past year on disorders of the spine, in this review, papers were chosen and grouped under five broad headings: 1) spinal trauma, 2) disk disease, 3) neoplastic disease, 4) spinal arthritis, and 5) other studies of interest. Although some of the articles chosen for review dealt with conventional radiography, the majority were on applications of CT and MR imaging to conditions affecting the spine. PMID- 1931509 TI - Imaging of musculoskeletal disorders in children. AB - A review of the year's literature on musculoskeletal disorders in infants and children includes many advances in imaging principles, especially MR imaging pulse sequences. We have not attempted to review these advances because the principles are essentially the same in children as in adults. We have confined this review to several topics including the importance of differentiating the findings in osteogenesis imperfecta from those in the abused child, limb lengthening procedures in infants and children, the treatment of slipped upper femoral capital epiphysis, spinal anomalies, and skeletal abnormalities associated with cloacal exstrophy. A brief comment on cervical spine films in pediatric trauma patients is also included. PMID- 1931510 TI - Imaging of arthropathies and disorders of connective tissue. AB - The evolution of diagnostic imaging has been recently characterized by a wish for a better understanding of pathogenesis of diseases and by technologic progress. Many authors published papers reexamining old myths and old concepts of osteoarthritis. Correlations between clinical data, radiologic data, and MR findings have allowed better definition of the characteristics of osteoarthritis of the knee. MR imaging is of great value in evaluating rheumatoid arthritis in the early stages and in certain locations such as the cervical spine and temporomandibular joint. New imaging techniques, especially CT and MR imaging, are also useful for accurately diagnosing Andersson lesions and cauda equina syndrome in ankylosing spondylitis as well as sacroiliac joint abnormalities in Crohn's disease. PMID- 1931511 TI - Radiographic and magnetic resonance imaging of bone and soft-tissue tumors and myeloproliferative disorders. AB - New experience and new information in the field of musculoskeletal tumors and marrow disorders continue to be dominated by MR imaging. Much of the new information builds on what already has been established by MR imaging, namely its unrivaled position in staging musculoskeletal tumors and demonstrating the extent of marrow disease. MR imaging has now been evaluated for quantitative estimation of tumor necrosis following neoadjuvant therapy for sarcomas, characterization of soft-tissue masses, and its role in the treated patient with marrow disease. This review also includes some publications in the field of musculoskeletal tumors on radiography and nuclear MR spectroscopy. PMID- 1931512 TI - Imaging in orthopedic surgery and other conditions of the musculoskeletal system. AB - Interest continues in total joint replacement and its complications. Now that noncemented arthroplasties have been introduced, further radiographic signs are being elucidated. The roles of bone scanning and aspiration arthrography are also being reevaluated. Ultrasonography has become the imaging modality of choice in congenital hip dysplasia and is being used increasingly in the evaluation of other musculoskeletal conditions. The ilizarov distraction osteogenesis technique is also discussed and there has been increasing interest in anterior cruciate ligament reconstruction and its sequelae. PMID- 1931513 TI - Genitourinary system. PMID- 1931514 TI - Musculoskeletal radiology. PMID- 1931515 TI - Mortality due to intestinal infectious diseases in Latin America and the Caribbean, 1965-1990. PMID- 1931517 TI - Cholera prevention and control: environmental health measures. PMID- 1931516 TI - Update: the cholera situation in the Americas. PMID- 1931518 TI - Surveillance of living conditions and the health situation. PMID- 1931519 TI - [University polyclinics]. PMID- 1931520 TI - [Regional hemodynamic evaluation of heterotopic liver transplantation by the determination of the hepatic artery resistance index]. AB - Hepatic artery resistance index (I.R.) was evaluated in six pigs through Doppler scan after progressive gauge reduction of the portal vein up to complete clamping. The I.R. values were (mean +/- S.D.): 0.48 +/- 0.01 in basal conditions; 0.37 +/- 0.03, and 0.33 +/- 0.01 with a reduction of 1/3 and 2/3 respectively; 0.27 +/- 0.02 after complete portal clamping. These data confirm the close relationship existing in the hepatic circulation between changes of the arterious resistence and those of the portal flow. The same animals, subsequently, underwent heterotopic liver transplantation in the right paracolic gutter. Immediately after surgery the I.R. values of the transplanted hepatic artery were recorded without clamping (basal portal flow 0.52 +/- 0.02) and after clamping of the transplanted portal vein (0.33 +/- 0.03), while maintaining clamped the recipient portal vein at the hilus. These values were comparable to those obtained in the recipient hepatic artery. These data suggest that, in spite of parenchymal damages secondary to surgical procedure and of the haemodynamically unfavorable site in which the organ is transplanted, heterotopic liver transplantation does not produce significant changes in hepatic arterious resistance. PMID- 1931521 TI - [Staging of gastric carcinoma and consequential therapeutic protocols]. AB - The Authors examine the most recent diagnostic methods of studying gastric carcinoma illustrating their limits and peculiarities. It is underlined that only an integrated use of these diagnostic methods may allow a right staging of the disease, which is very important for a correct therapeutic approach. After a review of the literature the Authors discuss on the extent gastric resection and lymphadenectomy must have to be considered radical and, at the same time, curative. PMID- 1931522 TI - [Splenic injuries: recent acquisitions concerning the treatment]. AB - The Authors briefly review spleen functions and the consequences of splenectomy particularly for what the immune function is concerned. Data concerning postoperative infections following splenectomy for staging laparotomy in 92 patients with lymphoma are analysed. Data concerning immunological function of 17 pts. who underwent splenectomy in the last 5 yrs. compared to 17 normal controls, homogeneous for sex and age, are reported. Plasma IgM decrease in 3 cases, CMI anergic status in 3 cases and CD4+/CD8+ lymphocyte ratio increase in 8 cases were observed. This article also reviews surgical techniques and recent knowledge in relation to the best treatment for splenic traumas, emphasizing advantages and disadvantages of conservative treatment. The Authors conclude presenting their personal series of 42 pts. affected with traumatic lesions of the spleen treated in the last 10 yrs., also illustrating a treatment flow-chart. PMID- 1931523 TI - [Local recurrence caused by direct implantation from cancer of the colon; findings of a case report]. AB - The Authors report the case of a 60 year old woman who developed a local recurrence 3 months after a right hemicolectomy for a cancer of the ascending colon. The site of the recurrence along the suture line, the huge size of the tumor, the short interval from the first operation with its apparent radicality strongly support the origin of such recurrence from implantation. Pathogenetic mechanisms of local recurrence due to implantation metastases as well as current methods to prevent tumor seeding in colorectal surgery are reviewed. The importance of early endoscopic follow-up after colorectal resection is also stressed. PMID- 1931524 TI - [Gastric leiomyoblastoma: analysis of a case and review of the literature]. AB - A case of gastric leiomyoblastoma of huge size together with immunohistochemical findings both on frozen and embedded sections is reported. The relevant literature on this rare but not exceptional neoplasm is reviewed. PMID- 1931525 TI - [Pyeloureteral junction syndrome caused by "anomalous vessel"]. AB - In presenting and describing the pathogenesis of the pyeloureteral junction syndrome, the Authors report their recent experience with four cases due to an "abnormal vessel". Symptoms, diagnosis, and surgical techniques are discussed. PMID- 1931526 TI - [Evaluation of the splenic function in patients with abdominal injuries undergoing splenectomy with autograft]. AB - Splenectomy, required for splenic injuries in which conservative management is unsuitable, causes a fall of the immunological defenses, increasing the risk of sepsis. Immunological functions of the spleen can be maintained by autotransplant of splenic tissue. This is confirmed in our experience by a comparative study of haematological, immunological and scintigraphic features in 14 patients. Autotransplantation was performed in 8 cases, while the remaining 6 cases were treated with simple splenectomy. PMID- 1931527 TI - [A rare cause of acute abdomen: perforation of cecal diverticulum]. AB - The Authors, after a brief review of the literature on the frequency and localization of large bowel diverticular disease report a case of perforation of a cecal diverticulum operated on emergency. They also add some brief comments on the interesting aspects of the case, its diagnostic difficulties and operating technique. PMID- 1931528 TI - [Formation of calculi on a double J catheter]. AB - A case of lithiasis due to indwelling double J ureteral stent is described. Pathogenesis and possibilities of prevention are discussed. PMID- 1931529 TI - [Endoscopic sclerotherapy of bleeding gastroduodenal ulcer. Our experience]. AB - The Authors report their experience in the treatment of bleeding gastric and duodenal ulcers by means of endoscopic sclerotherapy. From August 1988 to December 1989, 104 patients with haematemesis and/or melena were observed at the Clinica Chirurgica Generale, Toracica e Vascolare-Universita di Parma. Endoscopy, carried out in the first 24 hours, led to the diagnosis of a bleeding gastric or duodenal ulcer in 73 cases; 22 of these patients underwent emergency sclerotherapy using 1:10,000 Adrenaline in association with 1% Polydocanol. Results obtained are the following: absolute haemostasis in 20 patients (91%), and surgical intervention in the other 2 cases for renewed haemorrhage. Among patients endoscopically treated, one death (5%) was recorded. Further complications were not encountered. The Authors believe sclerotherapy is reliable and quick thus representing a considerable therapeutic advance in the treatment of gastroduodenal haemorrhage, notoriously at high death rate (8-10%). PMID- 1931530 TI - [Role of diaphanoscopy in breast diseases]. AB - The diagnostic value of diaphanoscopy in a series of 200 cases of breast diseases, all confirmed by cytohistologic examination, is illustrated. Diaphanoscopy showed a high sensitivity towards haemorrhagic cysts, early age fibroadenomas, adenosic dysplasia, haematomas as well as carcinomas. PMID- 1931531 TI - Appropriate investigation of gastrointestinal symptoms. PMID- 1931532 TI - A double-blind placebo-controlled trial of theophylline in general practice. AB - Patients with moderate to severe asthma, from two urban general practices, entered a double-blind randomised placebo-controlled crossover trial of sustained release theophylline versus placebo. Theophylline was given in therapeutic dosage (to ensure serum levels of between 10 and 20 micrograms/ml) for two months, followed by two months of placebo or vice versa. The results from the 24 patients who entered both theophylline and placebo treatment arms were compared, using outcome measures relevant to general practice care. Theophylline is shown to be of value in the management of asthma in general practice. PMID- 1931533 TI - Clinical audit of theophylline use in general practice. AB - The use of therapeutic drug monitoring for theophylline therapy was evaluated in two urban general practices. Of 55 patients studied, 44 (80%) had a sub therapeutic serum theophylline concentration, 11 (20%) had a therapeutic concentration (10-20 micrograms/ml), and none had an above therapeutic concentration. Patients were reviewed at weekly intervals and had their theophylline dosages adjusted according to serum levels. A therapeutic concentration was achieved in 37 patients (67%). This task proved to be 'laborious but not difficult'. Side-effects were less common than previous reports suggest. The general practice workload involved in adjusting theophylline dosage was approximately four consultations, one dose change and two serum assays per 'average' patient. PMID- 1931534 TI - The effect of sustained-release theophylline in nocturnal asthma. AB - Nocturnal symptoms are common and often disabling in asthmatic subjects. Furthermore, they often persist, in spite of appropriate dosages of inhaled beta 2-agonists and topical steroids. In such a clinical situation, theophylline preparations may have a therapeutic role. This double-blind, placebo-controlled, cross-over trial was designed to evaluate the effectiveness of a twice-daily Bioavail slow-release theophylline capsule in a group of out-patient asthmatics, with a history of nocturnal and/or early morning wheeze or chest tightness. Theophylline was initially prescribed and monitored in an 'open' phase to obtain the drug dosage required to achieve a serum level in the therapeutic range of 10 20 mg/l. In the ten patients who completed the study, serum theophylline levels were stable throughout. During active treatment there was an improvement in morning peak expiratory flow rate (PEFR), and a reduction in measurements of diurnal variation. In addition, the bronchodilator response to an inhaled beta 2 agonist was preserved. Bioavail theophylline has thus been shown to be an effective agent in the management of adults with nocturnal asthma. PMID- 1931535 TI - Patients' preferences for the site of injection of low-dose subcutaneous heparin in prophylaxis of thromboembolism. Regional acuphobia. AB - The efficacy of low-dose subcutaneous heparin in the prophylaxis of deep vein thrombosis and pulmonary embolism is now well established. The most common complication of heparin administration is haematoma formation, especially at the site of injection. A number of patients were noted to have injection site haematoma in the deltoid region: after close inquiry it was found that these patients had refused injections in the anterior abdominal wall in the belief that these would be more painful than the upper arm. A study was set up to determine the prevalence of regional acuphobia. PMID- 1931536 TI - An open, randomised, parallel group study of lactulose versus ispaghula in the treatment of chronic constipation in adults. AB - The efficacy, tolerance and acceptability of lactulose (Duphalac) and ispaghula (Fybogel Orange) were assessed in the treatment of chronic constipation in adults. In an open, prospectively randomised, parallel group study, 124 patients with a history of constipation for more than three weeks were treated with either 15 ml bd of lactulose (increasing to 60 ml daily if necessary) or one sachet bd of ispaghula. Over the four-week treatment period both treatments were shown to be effective, and numbers of concurrent effects were similar between the two groups. Differences were demonstrated with regard to acceptability in favour of lactulose. PMID- 1931537 TI - Why flush peripheral intravenous cannulae used for intermittent intravenous injection? AB - We aimed to investigate whether regular flushing of peripheral intravenous cannulae used for intermittent injections with heparin-saline, in a unit for acute medicine for the elderly, reduced the incidence of complications necessitating cannula removal. We wanted to see if this could also prolong the time that cannulae may remain functional in situ. In a prospective, open study, 50 consecutively inserted cannulae were flushed regularly and a subsequent 50 consecutive cannulae were not flushed. The incidence of complications necessitating removal was not significantly different between the two groups (18% flushed, 22% unflushed). Overall, only 5% of cannulae were removed because of blockage. Heparin-saline flushes did not significantly increase the time that cannulae remained in situ. Antibiotic use was found to be associated with an increased rate of complications necessitating cannula removal. We found no significant advantage in heparin-saline flushing of peripheral intravenous cannulae used for intermittent administration of medications. PMID- 1931538 TI - Massive haemorrhage in pancreatitis. AB - Massive haemorrhage in pancreatitis is a very rare complication of pancreatitis but it is the most rapidly lethal, haemorrhage being the major cause of death in more than half of the fatal cases. We present three patients who illustrate this rare complication in its diversity of presentation, and advise that doctors should have a keen clinical awareness of this condition if there is to be an effective and expeditious management. An understanding of the condition, coupled with immediate treatment, using embolisation or laparotomy with direct ligation of the bleeding vessel, can be lifesaving. PMID- 1931539 TI - Scabies in an AIDS hospice unit. AB - Scabies may cause severe problems in immunocompromised persons. Three case histories are presented which illustrate these problems in people with advanced AIDS. Recommendations for treatment and management are made, with a comment about the need for a high level of suspicion about any atypical rash in an immunocompromised patient. PMID- 1931540 TI - Jejunostomy feeding for the conservative management of spontaneous rupture of the oesophagus. AB - Three patients with spontaneous rupture of the oesophagus (Boerhaave's syndrome) were successfully treated by a conservative regimen consisting of nil orally and broad-spectrum antibiotics, while their nutrition was satisfactorily maintained by jejunostomy feeding. Such a regimen is simpler and cheaper than one utilising parenteral nutrition: it avoids its complications and limitations, and will enable healing to take place within three weeks after the rupture has occurred. It is therefore suggested that the conservative management of Boerhaave's syndrome is the treatment of choice. PMID- 1931541 TI - The dangers resulting from inaccurate computer-based operative records. AB - The accuracy of a computer-based recording system of operative procedures was audited at a major district general hospital. The system is supposed to provide accurate records of theatre activity, to allow for improved nursing resource allocation and provide surgeons with a basic record of their operations. Mistakes were present in the details of 27% of the cases entered. Such inaccuracies highlight a major danger to surgeons with regard to their accountability for operations attributed to them. Mistakes can only cause further problems with regard to audit and future resource allocation. PMID- 1931542 TI - A comparison of interpretation of screening mammograms by a radiographer, a doctor and a radiologist: results and implications. AB - In 1986, a project began to assess the feasibility of mobile breast screening, using oblique view mammography, in rural areas near Edinburgh. One of the aims of the project was to determine the feasibility, in terms of accuracy and cost, of non-radiologist prescreeners. The sensitivity and specificity of each reader was calculated (using 12-month interval cancer rates). Sensitivities of 80%, 80% and 83% were found for a radiographer, a non-radiologist doctor and a radiologist respectively, with corresponding specificities of 78%, 84% and 86%. When each reader was costed, prescreening was no cheaper than the radiologist reading all the films himself (79.10 pounds for the radiologist reading 1,000 pairs of films alone, against 84.97 pounds with the radiographer prescreening and 163.93 pounds with the non-radiologist doctor prescreening). We were unable to demonstrate any advantages of prescreening, but found that double reading of the films, though costly, would have increased the sensitivity of the programme. PMID- 1931544 TI - 'Them and us' philosophy in the treatment of AIDS. PMID- 1931543 TI - An audit of rectal examination on general/geriatric wards in a district general hospital. AB - A study of 187 in-patients on designated medical/geriatric wards revealed that rectal examination was performed as part of physical examination in only 25% of patients. In the elderly (118 patients) it was performed in 36%. A prospective analysis of 100 elderly patients, in whom digital rectal examination was performed, revealed that 46 patients had significant findings. In only 33 of these were there any gastrointestinal or genitourinary symptoms or signs. As a result of these findings it is recommended that digital rectal examination be considered mandatory in the elderly admitted into hospital. PMID- 1931545 TI - Pressurised aerosol inhalers: the cost of misuse. AB - Bronchodilator aerosols, if used correctly, have many advantages over other therapies in patients with chronic airflow limitation caused by asthma or chronic bronchitis. The use of pressurized aerosol inhalers was examined in a district general hospital: of 57 patients on these inhalers, 39 were unable to use the inhaler effectively, and 23 had never received any advice on inhaler technique. A single demonstration of correct technique decreased the failures to 21 patients and, after two demonstrations, to ten. The cost of the misused inhalers in this relatively small population was 450 pounds, and obviously this figure escalates when the prescription for these inhalers is repeated monthly. It is also increased when the total numbers of misused inhalers in the country are accounted for. The cost in terms of finance, in these days of medical audit and drug budgets, and, more importantly, in terms of patient health, is unacceptable and can be avoided by repeated tuition of technique. PMID- 1931546 TI - Medical eponyms updated: Bright's disease. PMID- 1931547 TI - Isolated endometriosis of the small bowel presenting as acute small bowel obstruction. AB - Although endometriosis is a common disease, small bowel involvement is unusual. We recently treated a patient in whom the diagnosis of endometriosis was made only after histological examination of a solitary lesion, which was obstructing the distal ileum and had the clinical appearance of a malignant tumour. PMID- 1931549 TI - Chest pain with normal coronary anatomy: further out of the closet. PMID- 1931548 TI - Persistent normal anion gap acidosis in the recovery phase of diabetic ketoacidosis. AB - Diabetic ketoacidosis is associated with an increased anion gap but its recovery phase may be complicated by hyperchloraemic acidosis with a normal anion gap. We report a case where this complication developed. There was a delayed return to normal acid-balance, possibly aggravated by administration of hyperchloraemic fluids, and the true diagnosis was overlooked. Measurement of the anion gap remains an important part of the assessment of diabetic acid-base disturbances. PMID- 1931550 TI - Unrecognised Cushing's syndrome and adrenal suppression due to topical clobetasol propionate. AB - A 53-year-old man with cushingoid appearance--obesity, osteoporosis causing lumbar and thoracic vertebral collapse and a past history of hypertension and depression presented with symptoms and signs of adrenocortical insufficiency. He denied the use of corticosteroid medication. However, it was eventually discovered that he had used clobetasol propionate (Dermovate), a potent topical steroid cream, for five years. The development of adrenal insufficiency symptoms coincided with the withdrawal of the cream. PMID- 1931551 TI - Patients with recurrent blackouts on carbamazepine therapy. AB - Two cases of cardiac syncope with epileptiform features are reported. The patients had been on carbamazepine for many months with increasing frequency of attacks until sinus arrest was documented. Their symptoms disappeared completely with permanent pacemaker implantation and anticonvulsant therapy withdrawal. PMID- 1931552 TI - Complicated peptic ulcer disease in childhood: an overlooked diagnosis. AB - Primary peptic ulceration is no longer regarded as a rare disease of childhood, but its exact incidence and pathogenesis remain debatable. We report the case of an 11-year-old boy, who presented with a perforated primary gastric ulcer, a rare complication in this age group. PMID- 1931553 TI - Gastric retention of swallowed coins after pyloromyotomy. AB - Swallowed coins are a frequent problem in paediatric practice. The majority that reach the stomach will pass unimpeded through the gastrointestinal tract. Prolonged gastric retention of a swallowed penny is reported in three children who had previously undergone pyloromyotomy for infantile hypertrophic pyloric stenosis. The coins were removed after laparotomy in two patients and endoscopically in the third. This abnormal retention may reflect a long-term disturbance of pyloric function after pyloromyotomy. PMID- 1931554 TI - Theophyllines in the treatment of asthma. PMID- 1931555 TI - Cerebral metabolism of fluorodeoxyglucose measured with 19F NMR spectroscopy. AB - Brain extracts from rats given various doses of 2-fluoro-2-deoxy-D-glucose ranging from 20 to 300 mg/kg were examined with 19F NMR spectroscopy for fluorinated metabolic products and compared with the in vivo 19F spectra. Based on the analysis of these spectra and comparison with synthetic reference compounds, 2-fluoro-2-deoxy-D-glucose 6-phosphate and 2-fluoro-2-deoxy-D-mannose 6-phosphate were identified as the major metabolites present. 2-Fluoro-2-deoxy-D 6-phosphogluconate was detected only at high doses of 2-fluoro-2-deoxy-D-glucose administered, along with non-phosphorylated 2-fluoro-2-deoxy-D-glucose and 2 fluoro-2-deoxy-D-mannose. Small amounts of two other compounds, which were not identified, were also observed. Presence of the 2-fluoro-2-deoxy-D-mannose 6 phosphate is the result of 2-fluoro-2-deoxy-D-glucose 6-phosphate isomerization at the C2 position catalyzed by phosphoglucose isomerase. Results from the in vitro enzymatic reaction provide support for this hypothesis. Presence of 2 fluoro-2-deoxy-D-mannose may be the result of 2-fluoro-2-deoxy-D-glucose isomerization at the C2 position catalyzed by glucose isomerase or the result of the dephosphorylation of the 2-fluoro-2-deoxy-D-glucose 6-phosphate. PMID- 1931556 TI - NMR estimation of protective effect of insulin on mouse liver with epinephrine induced metabolic lesions. AB - In order to study the effects of epinephrine and insulin on liver metabolism, measurements of cellular phosphates and intracellular pH by 31PNMR, of glycogen by 13C NMR and of lactate by 1H NMR were performed in freshly dissected mouse liver at 0-4 degrees C and in ethanolic liver extracts. The injection of epinephrine hydrochloride (0.1 mL of 0.1% solution i.p. per mouse) caused remarkable changes in liver metabolic profiles which were expressed most distinctly in 15-30 min and could not be attributed solely to epinephrine-induced hyperglycemia. Among these metabolic changes are falls in the levels of ATP and uridine diphosphate sugars by 60-70%, possibly related to glycogen depletion, and intracellular acidification by 0.5 units attributed to the release of protons during hydrolysis of ATP rather than to accumulation of lactate in anaerobic glycolysis. Insulin injected prior to epinephrine (4 units i.p.) markedly suppressed epinephrine-induced metabolic alterations, although the effect of the combination of insulin and epinephrine was not the sum of the separate effects of these hormones. The maximum protective effect of insulin was reached when insulin was injected 15 min prior to epinephrine. The results obtained demonstrate the applicability of NMR for evaluating the protective activity of modifiers at various extreme exposures. PMID- 1931557 TI - 1H NMR spectroscopic imaging of the monkey brain using binomial water suppression in a stimulated-echo sequence. AB - A new proton, two-dimensional pulse sequence for 1H NMR spectroscopic imaging (chemical shift imaging) was tested in phantoms and in the monkey brain. The pulse sequence consisted of one binomial chemically selective pulse and two spatially selective pulses in the stimulated-echo sequence. The point-spread function (which is influenced by k-space filtering and the number of phase encoded steps) of a 1 mm source phantom was measured using a 16 x 16 spatial matrix and was found to have a FWHM of 10 mm (100 mm field of view) with very little rippling outside the main lobe. The binomial excitation profile was measured in order to correct the NMR intensity for the variable flip angles. Spectroscopic images were measured in the monkey brain with a 15 mm slice thickness and a 16 x 16 spatial matrix. Proton spectra derived from the brain contained sharp resonances of choline, creatine and N-acetyl aspartate with minimal lipid contamination. Proton spectra derived from the subcutaneous fat and adipose tissue behind the eyes contained large lipid resonances. PMID- 1931559 TI - Comments on the NMR visibility of 23Na in skeletal muscle. PMID- 1931558 TI - 1H NMR characterization of normal human cerebrospinal fluid and the detection of methylmalonic acid in a vitamin B12 deficient patient. AB - 1H NMR was used to analyze human cerebrospinal fluid (CSF) from a group of neurological disease controls and from a vitamin B12 deficient patient. The spectra were acquired at either 7.06 or 9.40 T at ambient temperature with CSF freeze dried and reconstituted in 2H2O. 3-Trimethylsilyl propionate was used as an internal chemical shift and concentration reference. All of the CSF samples showed peaks for lactate, L-alanine, acetate, glutamine, citrate, creatine/creatinine and sugar resonances. There was good agreement between the metabolite concentrations as determined by NMR with those obtained using conventional chemical methods. 1D and 2D 1H NMR techniques along with J-coupling and T1 analysis were used to confirm the peak assignments. Methylmalonic acid could be detected and quantitated (ca 150 microM) in the CSF from the vitamin B12 deficient patient. PMID- 1931560 TI - Internal medicine and dermatology. PMID- 1931561 TI - Newer aspects of inflammatory bowel disease and its cutaneous manifestations: a selective review. AB - Idiopathic inflammatory bowel disease (IBD) denotes several types of gastrointestinal disorders characterized by protracted inflammation of the large or small bowel, and a tendency toward relapse or recurrence. The two major groups of IBD are identified as chronic nonspecific ulcerative colitis (UC) and Crohn's disease (CD). Extraintestinal manifestations of IBD are diverse and may antedate, occur with, or postdate the onset of the disease process itself. Cutaneous diseases such as erythema nodosum or pyoderma gangrenosum are not infrequent, and test the clinician's ability to recognize the underlying bowel pathology and institute appropriate treatment. This selective review will address the immunological pathogenesis of IBD, new or rarely reported skin markers in IBD, drug therapy and side effects, zinc deficiency, management of osteotomy patients, and cutaneous cancer complicating IBD. Although the prognosis of IBD has improved, the role of the dermatologist as a consultant remains invaluable in reducing the attendant cutaneous morbidity. PMID- 1931562 TI - Cutaneous and cardiac myxomas: an important association. AB - Carny and others have described the association of cutaneous myxomas and various nevomelanocytic neoplasms with cardiac myxomas and endocrine neoplasms. The association between cutaneous and cardiac myxomas is especially important in view of the potentially serious, even fatal, embolic sequelae of the latter neoplasm. PMID- 1931563 TI - Antiphospholipid syndrome and cutaneous vasoocclusive disorders. AB - The antiphospholipid syndrome (characterized by the presence of circulating lupus anticoagulants or anticardiolipin antibodies) was first recognized in patients with systemic lupus erythematosus (SLE), but the syndrome can also exist in the absence of SLE. The clinical features include arterial or venous thrombosis, recurrent abortion, neurological problems, and various cutaneous disorders including thrombophlebitis, livedo reticularis, atrophie blanche, leg ulcers, and gangrene. In some cases, antiphospholipid antibodies may play a role with other recognized syndromes characterized by vascular occlusion, such as Sneddon's syndrome (livedo reticularis with cerebrovascular occlusion) and Degos' disease. PMID- 1931564 TI - Acanthosis nigricans. AB - Acanthosis nigricans (AN) is a dermopathy with a distinctive appearance that facilitates its diagnosis. Although an external condition, it is associated with a wide variety of less obvious internal conditions, either benign or malignant. Insulin resistance figures prominently in its benign associations and plays a primary role in its development. The development of AN in malignant conditions remains to be explained. AN rarely requires treatment, although the underlying condition usually does. PMID- 1931565 TI - Recent advances in the molecular biology of cutaneous lymphomas and related disorders. AB - This article discusses the study of cutaneous lymphoid infiltrates using analysis of immunoglobulin and T-cell receptor gene rearrangements with special emphasis on the Southern blot technique, determining the clonality of specific dermatoses, the issue of clonality versus differentiation, the use of molecular biologic methods for staging and related applications, and the pitfalls inherent in the interpretation of Southern blots. Other topics discussed include molecular cytogenetics, gene amplification using the polymerase chain reaction, in situ hybridization, and the immunohistologic interface between molecular biology and immunohistology. Key points and future directions for the role of diagnostic molecular biology in cutaneous lymphoproliferative disorders are also considered. PMID- 1931566 TI - Dermatologic changes associated with adoptive immunotherapy of cancer. AB - One of the major areas of biomedical investigation has been the development of new methods to treat metastatic cancers. Since the early 1980s, Steven Rosenberg and his colleagues at the National Cancer Institute have been developing a new therapy using lymphocytes from patients with cancer. This treatment has been termed "adoptive immunotherapy" because it involves the infusion of lymphokine activated killer (LAK) cells generated in vitro; interleukin-2 (IL-2) is also infused, which generates more LAK cells in vivo. Continued studies of this experimental treatment have demonstrated promising results in the mediation of regression of advanced cancers. However, this immunotherapy is extremely toxic, inducing a widespread capillary leak syndrome that affects virtually all organ systems, including the skin. Clinical and laboratory evaluation of the skin and other organ systems have shown new information concerning the mechanisms of action of this immunotherapy, along with mechanisms of toxicity. This information is being used to maximize the therapeutic effect (ie, tumor regression) while minimizing toxic reactions. PMID- 1931567 TI - Immunopathology of leprosy skin lesions. AB - These immunopathogenesis studies of leprosy have provided new insight into the immune response to M leprae at the site of disease activity, the skin lesions. The study of leprosy provides a model for studying the immune response to foreign pathogens as well as the immunopathologic study of skin lesions. Further developments in immunology and molecular biology will increase our ability to dissect such immune mechanisms. For example, the advent of the polymerase chain reaction will allow for a more complete elucidation of the cytokines in inflammatory skin lesions. PMID- 1931568 TI - Bacillary angiomatosis: a systemic opportunistic infection with prominent cutaneous manifestations. AB - Bacillary angiomatosis is an opportunistic infection with systemic manifestations. Although most cases have occurred in human immunodeficiency virus positive patients, other immunosuppressed patients, and even seemingly immunocompetent individuals, can become infected. In addition to the well characterized cutaneous manifestations, visceral involvement can occur and may be the only locus of infection. Lymphadenopathy, bone or soft-tissue masses, fever, and hepatosplenomegaly can be presenting signs. The causative bacterium is still unidentified, but resemblances to the rickettsiae, Rochilamea quintana, the recently identified cat-scratch disease bacillus, and Bartonella bacilliformis have been noted by various investigators. Systemic disease is treatable and can be cured with antibiotic therapy. PMID- 1931570 TI - Autoantibodies in scleroderma and polymyositis: an update. AB - Cutaneous manifestations of systemic connective tissue diseases, such as scleroderma and its variants, polymyositis, and dermatomyositis, often prompt early dermatologic consultation. Indirect immunofluorescent autoantibody determinations using tissue culture substrates are initial screening tests that are highly positive in the majority of patients with scleroderma and its variants, but are less frequently positive in patients with polymyositis and dermatomyositis. When combined with second-level analyses for the multiplicity of precipitin autoantibodies that have been defined in both these major classes of rheumatic diseases, most autoantibodies of both diagnostic and prognostic significance can be defined efficiently and cost-effectively. The major autoantibody specificities characteristic of these connective tissue diseases are summarized in this article, with emphasis on current concepts of their clinical molecular, and possible pathogenetic significance. PMID- 1931569 TI - Molecular characterization of the Ro/SS-A autoimmune response. AB - Human Ro/SS-A (Ro) antibodies (anti-Ro) are frequently seen in the circulation of patients with several subsets of photosensitive cutaneous lupus erythematosus (LE) and related disorders. Experimental observations have suggested that anti-Ro reacting with Ro antigens that are expressed abberantly within the epidermis might play a causal role in LE-specific skin disorders such as subacute cutaneous LE (SCLE) and neonatal LE. In this article, we will review the progress that has recently been achieved toward gaining a better understanding of the molecular configuration, genetic regulation, and function of the Ro ribonucleoprotein (RNP) antigenic complex as well as the autoimmune response with which it is associated. Work in this area has recently revealed the existence of multiple Ro autoantigen bearing polypeptides including a 46-kd Ro protein that is virtually identical to calreticulin, a highly conserved, calcium-binding protein that is normally associated with the endoplasmic reticulum. The implications of these observations with respect to the pathogenesis of anti-Ro-associated LE skin lesions are explored. PMID- 1931571 TI - Autoimmune mechanisms in psoriasis. AB - Psoriasis is a chronic papulosquamous skin disorder affecting 1% to 3% of the general population. There is increasing evidence that immunologic mechanisms are involved in the pathogenesis of psoriasis, and that a link between psoriasis and autoimmunity may exist. A variety of autoantibodies has been observed in psoriasis including antinuclear antibodies, antibodies to small nuclear and cytoplasmic ribonucleoproteins, and antibodies to epidermal cells. UV light treatment of psoriasis may play a role in inducing these autoantibodies in some individuals. Recent evidence that activated T cells in psoriatic plaques may produce interferon-gamma leading to the appearance of ectopic class II major histocompatibility products on the surface of keratinocytes also supports the idea of a link between psoriasis and disordered immunoregulation. The immunologic abnormalities in psoriasis and the association of psoriasis with particular types of autoantibodies raise the possibility that a common etiology may underlie both psoriasis and autoimmunity in some patients, but the different responses of the two diseases to UV light treatment and certain pharmacological agents suggest that psoriasis may not have an autoimmune pathogenesis. PMID- 1931572 TI - Autoimmunity to type VII collagen. AB - The epidermolysis bullosa acquisita (EBA) antigen is type VII collagen that is found within the anchoring fibrils of the basement membrane zone beneath stratified epithelia. Autoimmunity to the EBA antigen/type VII collagen has been associated with three diseases: EBA, bullous systemic lupus erythematosus (SLE) and a subset of linear IgA bullous diseases. Although some systemic diseases in which autoimmunity is thought to play a role (eg, inflammatory bowel disease, thyroiditis) have been reported in association with EBA, so far there have not been systemic diseases associated with autoimmunity to type VII collagen other than SLE. In the case of EBA and bullous SLE, it appears that many patients may have a genetic predisposition toward autoimmunity because they share a human leukocyte antigen (HLA) major histocompatibility (MHC) class II cell surface protein, HLA-DR2. The full clinical spectrum of EBA and perhaps other diseases in which there is an association with autoimmunity to type VII collagen is currently being defined. PMID- 1931573 TI - Immunogenetics of dermatitis herpetiformis. AB - Dermatitis herpetiformis (DH) is a pruritic, papulovesicular skin disease characterized in part by the presence of granular deposits of IgA at the dermal epidermal junction, an associated gluten sensitive enteropathy (GSE), and a strong association with specific human histocompatibility leukocyte antigens (HLA). Initial investigations revealed that 60% to 70% of patients with DH expressed the HLA antigen B8 (normal subjects = 21%). Further investigation of the HLA associations seen in patients with DH has revealed an even higher frequency of the HLA class II antigens HLA-DR3 (DH = 95%; normal = 23%), HLA-DQw2 (DH = 100%; normal = 40%), and HLA-DPw1 (DH = 42%; normal = 11%). Analysis of the genetic linkage of HLA antigens has revealed that the strongest HLA association in patients with DH is with the HLA class II antigens DR3 and DQw2. This article will discuss current studies regarding the role of HLA associations and DH and the role this strong HLA association may play in the pathophysiology of DH. PMID- 1931574 TI - The pathogenic role of growth factors in melanoma. AB - Some early changes associated with atypical nevi, presumed to be progressing toward malignancy, include chromosomal abnormalities and altered production of growth factors, and/or growth factor receptors. Though normal epidermal melanocytes require a number of exogenous growth factors, nevi require fewer growth factors, and most metastatic melanomas are frequently capable of growing without an exogenous supply of growth factors. This is apparently caused by endogenous production of essential growth factors. Our laboratory focuses on melanoma growth stimulatory activity (MGSA), one of the endogenously produced growth factors, and the role it plays in tumor progression. MGSA is a member of the beta-thromboglobulin super family. These genes code for cytokines, which modulate the inflammatory response. The MGSA protein is highly chemotactic for neutrophils and competes with 125I-interleukin-8 for binding sites on neutrophil receptors. When normal immortalized mouse melanocytes are manipulated so that they overexpress the MGSA gene, the melanocytes form large colonies in soft agar and melanoma tumors in nude mice. These data suggest that the MGSA protein can potentially play a role in melanoma tumor progression. PMID- 1931575 TI - Cell adhesion molecules and cutaneous inflammation. AB - Cutaneous inflammation is characterized by the infiltration of leukocytes such as polymorphonuclear neutrophils (PMNs), lymphocytes, and monocytes into the epidermis, dermis, or subcutaneous tissue in response to infectious or immunologic stimuli, in wound healing, or in response to trauma. In recent years, it has been found that cell-surface proteins on leukocytes, endothelial cells, and keratinocytes are critical elements in the initiation and evolution of cutaneous inflammation. In order for peripheral blood leukocytes to leave the circulatory system and enter tissue parenchyma, they must first bind to endothelial cells, pass between them, and traverse the vascular basement membrane. In this article we will examine both leukocyte-endothelial cell binding and evidence indicating that various cell-surface molecules present on leukocytes and endothelial cells, known as cell adhesion molecules (CAMs), interact with one another in specific fashion. This interaction or binding is a critical occurrence and its inhibition leads to downregulation of inflammation. Furthermore, some CAMs can be either induced or upregulated on leukocytes and endothelial cells by various proinflammatory cytokines. This tends to upregulate inflammation. It has become increasingly clear that the time-course of inflammation and its exquisite anatomic specificity are related to the regulation of expression of CAMs. PMID- 1931576 TI - Global programme on AIDS. PMID- 1931577 TI - Acquired immunodeficiency syndrome (AIDS). PMID- 1931578 TI - Relapsing fever. Outbreak at the Grand Canyon National Park, Arizona, 1990. PMID- 1931579 TI - Diarrhoeal disease control (CDD) programme. PMID- 1931580 TI - Shigellosis. Shigella dysenteriae type 1. PMID- 1931581 TI - Diarrhoeal disease control programme. Household survey of diarrhoea case management. PMID- 1931582 TI - Measles in 1990. PMID- 1931583 TI - Human plague in 1990. PMID- 1931584 TI - Prevalence of chronic migraine headaches, 1980-1989. PMID- 1931585 TI - Global programme on AIDS and global blood safety initiative. Recommendations for testing for HIV antibody on serum pools. PMID- 1931586 TI - Readership survey. PMID- 1931587 TI - Traffic accidents. Safety-belt use among drivers involved in alcohol-related fatal motor-vehicle crashes, 1982-1989. PMID- 1931588 TI - To all members of the American Association for Cancer Education. PMID- 1931589 TI - A strategy to teach medical decision making within a medical school curriculum. AB - One of the goals of our medical school is to teach our students how to learn. In theory, this is a noble goal, but, in practice, our style is often to "impart" our knowledge to the students without allowing them to question it, to practice with it, and to really understand it. To address this problem, we are developing a vertically integrated four-year program in medical decision making funded by the Culpeper Foundation. The curriculum begins with classic epidemiology in year one. In year-two courses, principles of clinical epidemiology (diagnosis, variability, etc) and the elements of quantitative decision making are woven into our organ system courses. In year three, these skills are practiced in clerkships, and critical thinking sessions occur in several clerkships. The curriculum culminates in year four with sessions on expected value decision analysis in one of our required courses. Built into this experience are computer interactive programs, faculty and housestaff development sessions, and availability of consultation from a medical decision making team. We are developing competency-based exams in which students will have to demonstrate skills in medical decision making, critical thinking, and problem solving. We hope this will help teach our students "how to" make decisions and understand such things as critical thinking, probability, uncertainty, and variability. Through this, we hope the decisions they will help their patients make will lead to the "best" outcomes for these patients. PMID- 1931590 TI - Teaching epidemiology and biostatistics through interactive problem solving. AB - Medical education should prepare students for the reasoning and decision making that are required in a physician's clinical work. The disciplines of epidemiology and biostatistics, as combined in clinical epidemiology, lend themselves very well to this purpose. A lecture course in epidemiology and biostatistics was redesigned to emphasize interactive learning through problem-solving workshops in which students worked with actual data from two epidemiologic studies. A third workshop provided experience in the critical appraisal of an epidemiologic study from the current literature. Students respond favorably to these active learning experiences, which deal with relevant contemporary health problems. The concepts of clinical epidemiology should be integrated into clinical teaching in all stages of training. PMID- 1931591 TI - A clinical cancer prevention curriculum in a comprehensive cancer center. AB - Interns, residents, and medical students who spend one month at a comprehensive cancer center are presented with a strategy to incorporate cancer preventive services into their outpatient practices. This is accomplished through didactic lectures in clinical epidemiology. Terms that are essential to an understanding of disease occurrence are defined including incidence, prevalence, and mortality rate. Odds and probability are explored with the introduction of the odds ratio and the identification of risk factors. Primary and secondary cancer prevention are defined, and parameters related to cancer screening are introduced (sensitivity, specificity, prevalence, and positive predictive value). Risk factors for malignancy are identified where they are known and can be modified. Primary prevention strategies are reviewed by site along with data that support or refute recommendations for site-specific screening. Medical conditions and risk factor profiles that define high-risk groups are reviewed. Trainees are given copies of the US Preventive Services Task Force screening recommendations and a clinical handbook. The impact of this information on clinical practice patterns remains to be evaluated. PMID- 1931592 TI - Development of critical appraisal skills in medical students: opportunities in oncology-related learning situations. AB - Considering the increasing need for medical students to acquire critical appraisal skills, we have reviewed the curriculum at McGill as to where and how this subject is taught. It is apparent that critical evaluation is covered formally and informally in the course of the four years of medical school. However, this effort is limited by other demands on curriculum time. It could be extended by practical applications, utilizing opportunities arising in oncology related learning situations, identifiable during periods of clinical electives, clerkship and options, and laboratory research. The elements of a core curriculum to develop critical appraisal skills and a pertinent bibliography have been identified. This information will be transmitted to oncologists supervising medical students, with the intention of eventually providing it to teachers in other specialties with the hope thereby of reaching all medical students. Concurrently, means of evaluating the method and results need to be formulated. PMID- 1931593 TI - Impact of the Cancer Education Program on career paths of students. AB - A questionnaire sent to former University of North Carolina students who participated in the Cancer Education Program, a National Cancer Institute sponsored program designed to provide integrated educational opportunities in oncology for students in the health science schools, ascertained the career paths taken by students and elicited opinions regarding the impact of the program on those decisions. One hundred five surveys were returned. The opportunity to be involved in cancer research was the most common reason given for participation in the program (65 respondents). The opportunity to work with a specific faculty member (48) and improving academic credentials (44) were also important. Twenty three individuals changed their career goals after participation in this program, 20 decided to pursue cancer-related careers, and 3 decided to avoid this field. One hundred three individuals were currently in health professions, 58 in academic, and 45 in community-based practice. Twenty-seven were not involved with cancer, while 56 spent up to 25% of their professional time, 8 spent 25%-50%, and 9 spent over 50% of their professional time in cancer-related activities. PMID- 1931594 TI - A survey in general practice about undergraduate cancer education: results from Gironde (France). AB - In Bordeaux University (France), oncology teaching was individualized in 1972, and an optional oncology course devoted to general practice was created in 1980. To evaluate the adequacy of these two oncology classes for general practitioners and so to adapt our current teaching, we sent to each of 1,219 general practitioners (GP's) of Gironde (county of the southwest of France) an anonymous questionnaire about oncology teaching in prevention, screening and cancer detection, cancer management, and curriculum balance. We received 688 (56.4%) responses. GPs said that as undergraduates, they were insufficiently instructed about screening programs (65%), pain control (80%), palliative care (50%) and fundamental or biological data (greater than 55%). This situation, which showed signs of improvement from 1975 on, has improved even more since 1985. General practitioners, as well as undergraduates, are not yet adequately educated about cancer for general practice, so we have to adapt better our current teaching for undergraduates and those in continuing medical education. PMID- 1931595 TI - Reviewing graduate medical education programs: a cancer center experience. Members of the Graduate Training Committee. AB - The Graduate Training Committee at Memorial Sloan-Kettering Cancer Center developed procedures for comprehensively reviewing the 32 graduate training programs at our institution. The methods used to carry out this review, the problems encountered, and the results of this review are presented. As this type of program review is now mandated by the Accreditation Council for Graduate Medical Education (ACGME), our method and experience should prove useful to other institutions planning a similar review process. PMID- 1931596 TI - Improving accrual into cancer clinical trials. AB - It is thought by some that there are inadequate patient entries on high priority national cancer treatment protocols, resulting in intolerable delays in addressing crucial research issues. The North Central Cancer Treatment Group in Rochester, Minnesota generated a questionnaire with possible impediments to patient treatment entry as well as suggested measures for approving accrual. Of 334 questionnaires, 63% were completed and returned by medical oncologists, radiation therapists, surgeons and nurse/data managers. The most frequently listed impediments included patients' advanced age or fragility, inadequate health insurance, and excess travel distance. Protocol concerns included too many tests that were too complex and too costly. Practice concerns included physicians too busy and inadequate help. Suggestions toward improving patient accrual included subsidizing drugs, subsidizing nonessential tests for patient care, and increasing funding for support personnel. Popular suggestions for education efforts included teaching the importance of clinical trials, emphasizing personal benefit to the patient and recognition of physicians and institutions participating. It was felt that protocols should be simplified, be more consistent with practice, and be more flexible. These considerations are relevant not only in the interests of more effective clinical research but also in the interests of appropriate education of residents and oncology fellows involved in clinical trials. PMID- 1931597 TI - Role of the general practitioner in breast cancer screening in The Netherlands. AB - Following the advice of the Dutch National Health Council, a national screening program for breast cancer was started in 1990 in the Netherlands. All women aged 50-70 will be invited for screening by mammography in fixed or (semi)mobile screening units every 2 years. The role of the general practitioner in screening for breast cancer is described in the Dutch protocol (Standard) published in 1990 by the Dutch College of General Practitioners. Because of the role of the general practitioner/family doctor as a gatekeeper and because of the list system, every Dutch woman is known by her own general practitioner. In any given year the general practitioner will see 70% of his population. So the general practitioner is in the position to play an important role in practice and patient-centered support of breast cancer screening. The general practitioner also has an important role in the support of women with positive results. The general practitioner receives the "abnormal" results and has to explain to the woman what this means and what further investigations are necessary. There are teaching programs on screening for breast cancer for the vocational training of general practitioners and for postgraduate training. PMID- 1931598 TI - Improving breast self-examination training by using the 4MAT instructional model. AB - Women were taught breast self-examination (BSE) two different ways using the same material. The 4MAT presentation (N = 49) was directed to four learning styles and both brain hemispheres; the American Cancer Society (ACS) presentation (N = 45) used a traditional lecture/discussion format. A control group (N = 58) was untrained. The mean age of the Cooperative Extension Home Demonstration Club participants was 57 years. A questionnaire, which was given before training, immediately after training, and 3 months later, assessed knowledge of breast cancer and BSE, confidence in performing BSE, and frequency of BSE. ANCOVAs and t tests showed that, compared with the ACS presentation, the 4MAT presentation produced better immediate acquisition and better 3-month retention of both knowledge and confidence. Both 4MAT and ACS participants were statistically superior to the control group on all three dependent variables, both in acquisition and 3 months later. The 4MAT instructional model is recommended for BSE and other health education presentations. PMID- 1931599 TI - Aberrant expression of intestinal mucin antigens associated with colorectal carcinoma defined by a panel of monoclonal antibodies. AB - Small intestine mucin antigen (SIMA) is an oncofoetal antigen for the colon and is distinct from the normal large intestinal mucin antigen (LIMA). In the present study, a panel of anti-SIMA and anti-LIMA monoclonal antibodies (MAb) was used to charaterise altered mucin expression in colorectal adenocarcinomas, by immunohistochemistry and quantitative immunoassays of tissue extracts. These results are compared with CEA expression and correlated with various clinicopathological indices. All mucin MAb reacted with a high proportion of the 100 colon cancers of every stage, histological type (including non-mucinous cancers), differentiation, site, or size. Inappropriate SIMA production was detected by either anti-SIMA MAb 4D3 or 4A1, even in 85% of early stage cancers. MAb 4D3 reacted with a higher proportion of cancers of smaller size and better differentiation. At the subcellular level, both anti-SIMA MAb showed reactivity typical of normal mucin, i.e., goblet cell and extracellular mucin. The normal colonic antigen, LIMA, was also detectable in the majority of cases, but quantitatively overproduced in some cases and reduced in others. However, in contrast to SIMA, LIMA was detected in predominantly undifferentiated cancer cells but not in goblet cells. Heterogeneity of MAb reactivity between cases and complementarity within each cancer was frequently observed. Mucin reactive with at least one of the MAb was detected in all of the CEA-negative cancers. A high rate of inappropriate SIMA expression was also detected in the perineoplastic transitional mucosa (88%, c.f. CEA, 35%) and adjacent, morphologically normal mucosa (80% c.f. CEA, 24%), indicating biochemical changes similar to the cancer. This panel of anti-mucin MAb demonstrated altered mucin glycoprotein metabolism associated with the development and progression of most colorectal cancers, which emphasises their utility as indicators of neoplastic change in the colon, and their superiority to CEA. PMID- 1931600 TI - Changes in expression of cellular oncogenes and endogenous retrovirus-like sequences during hepatocarcinogenesis induced by a peroxisome proliferator. AB - Previous studies have demonstrated that BR-931, a hepatic peroxisome proliferator, can induce liver tumours in mice and rats. Since alterations in gene expression may play a critical role in multistage hepatocarcinogenesis, the present studies examined the expression of the c-myc, c-H-ras, epidermal growth factor (EGF) receptor and ODC (ornithine decarboxylase) genes, as well as endogenous retrovirus-like sequences, in F344 rat liver during the first 8 weeks of feeding a 0.16% Br931 diet and in liver tumours induced by chronic feeding of this diet. Northern blot analysis of poly A + liver RNA samples showed an increase in the level of RNAs homologous to rat leukaemia virus (RaLV) but no significant change in the level of 30S-retrovirus related RNAs in the liver RNA samples obtained from rats during the first 8 weeks of feeding the diet containing BR931. An increase in the levels of c-myc, c-H-ras and ODC transcripts was also seen in the liver RNA samples from the treated rats. Of particular interest was a decrease in the abundance of EGF receptor transcripts in the liver RNA samples from rats fed the BR931 diet. Increased levels of RaLV, c-myc, and ODC RNAs were also seen in the tumours induced by BR931, but this was not the case for 30S and c-H-ras. The liver tumour samples also showed a decrease in EGF receptor RNA. These changes in cellular levels of specific RNAs resemble, in several respect, those we previously described in rodent liver during regeneration and tumour promotion, and also those seen in rodent hepatomas induced by other agents. Therefore, they may reflect a common profile of gene expression relevant to liver proliferation and carcinogenesis. PMID- 1931601 TI - The phosphocholine and glycerophosphocholine content of an oestrogen-sensitive rat mammary tumour correlates strongly with growth rate. AB - An oestrogen sensitive rat mammary tumour was grown in two groups of female and one group of male hooded rats. The male group and one of the female groups were supplemented with oestrogen. The tumours grew most rapidly in the female supplemented group. When the tumours reached 1.5 cm in diameter they were harvested and the cell cycle distribution and number of cells actively synthesising DNA (bromodeoxyuridine (BrdU) labelling index) determined in each case. Chemical extracts were prepared from each tumour and the concentration of phosphorus-containing metabolites determined using high resolution NMR spectroscopy. The concentration of phosphocholine was found to correlate strongly with the number of cells in S-phase and the number of cells labelled with BrdU, whilst a highly significant negative correlation was observed between these two parameters and glycerophosphocholine. The concentration of phosphoethanolamine did not correlate with either of these measures of proliferation rate. The concentration of glycerophosphorylethanolamine showed a weak negative correlation with the number of cells in S-phase. PMID- 1931602 TI - Photocytotoxic efficacy of sulphonated species of aluminium phthalocyanine against cell monolayers, multicellular spheroids and in vivo tumours. AB - The problem of relying solely on in vitro data to predict photosensitiser efficacy was demonstrated by examining the uptake and the ability to mediate photocytotoxicity of mono-, di-, tri- and tetra-sulphonated species of chloroaluminium phthalocyanine (AlS1-4Pc) in monolayer cultures of murine Colo 26 cells and in both monolayer and spheroid cultures of human WiDr cells. Cells treated in vitro, whether in monolayer or as spheroids, with the less sulphonated derivatives, AlS1Pc and AlS2Pc, were more susceptible to photocytotoxicity than those treated with AlS3Pc, cells treated with AlS4Pc were even less susceptibile to the cytotoxic effects of light irradiation. Generally these results mirrored the cellular uptake in vitro. When WiDr spheroids were increased in size from 250 microns to 500 microns there was a reduction in uptake of AlS1Pc and AlS2Pc which was reflected by the decreased sensitivity of the larger spheroids to the effects of light irradiation. AlS1Pc had no effect against Colo 26 cells growing as s.c. tumours in syngeneic BALB/c mice; whereas AlS3Pc, AlS2Pc and AlS4Pc produced significant reductions in tumour weights 5 days post laser light irradiation. Of these, AlS2Pc had the most dramatic effect on the colony forming efficiency of tumour cells recovered 24 h after PDT. While, despite their effects on tumour size, AlS3Pc and AlS4Pc scarcely affected the subsequent viability of cells from dissociated tumours. Thus the in vitro efficacy of the sulphonated species of phthalocyanines is not necessarily predictive of their in vivo effectiveness. PMID- 1931603 TI - The renal effects of N10-propargyl-5,8-dideazafolic acid (CB3717) and a non nephrotoxic analogue ICI D1694, in mice. AB - N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)- N-methylamino]-2 thenoyl)-L-glutamic acid (ICI D1694) is an analogue of the thymidylate synthase inhibitor, N10-propargyl-5,8-dideazafolic acid (CB3717). CB3717 was found to be active in early clinical studies, but its use was limited by nephrotoxicity. ICI D1694 is a more potent antitumour agent than CB3717 and is also more water soluble. Previous studies have shown ICI D1694 to be non-toxic to the kidney following a single administration but its renal effects after chronic administration are unknown. To assess these effects, and further define the time course and dose relationship of CB3717-induced renal damage, an assay of glomerular filtration rate (GFR) has been developed which can be used in mice and hence in the screening of novel compounds. The 14C-inulin clearance assay developed was used to show a linear relationship between CB3717 dosage and renal damage (r = - 0.989) following a single bolus dose (50-200 mg kg-1), in mice. CB3717-induced renal damage is persistent (greater than 6 weeks) and renal scarring was noted. ICI D1694 has been shown to be non-nephrotoxic following weekly administration of 250 mg kg-1 for 6 weeks. Measurement of GFR has been shown to be a more sensitive indicator of impaired renal function than plasma urea and creatine concentration, and the measurement of plasma creatinine concentration in particular, appears to be without value in the screening of potential nephrotoxins in certain mouse strains. PMID- 1931604 TI - Glutathione restores normal cell activation and cell cycle progression in cis platinum treated human lymphocytes. AB - Cis-platinum (CDDP) induces severe inhibition of cell activation and cell cycle progression in PHA-stimulated human PBL's. Applying the novel BrdU/Hoechst flow cytometric technique for high resolution cell cycle analysis we show that CDDP induced multiple cell kinetic disturbances occur simultaneously comprising G0/G1 arrest, and slow down and arrest of cells in S and G2/M-phase. We investigated whether the administration of reduced glutathione (GSH) might rescue cells from proliferative disturbances induced by CDDP. GSH at 0.15 mg ml-1 only partially restored normal cell activation and cell cycle progression. However, at 1.5 mg ml 1 a complete normal proliferation pattern was obtained. At the highest GSH dose rescue from inhibition of cell activation (G0/G1-phase arrest) as well as of cell cycle progression (S- and G2/M-phase arrest) was also present after delayed addition of GSH (1, 4 and 20 h) to CDDP treated PBL's. In addition cell viability of CDDP exposed PBL's is restored after GSH treatment. Our in vitro experiments give evidence that an increase of WBC found in CDDP/GSH treated patients has a real underlying cellular physiological mechanism protecting human peripheral lymphocytes from CDDP toxicity. PMID- 1931605 TI - The effect of circulating antigen and radiolabel stability on the biodistribution of an indium labelled antibody. AB - This study has investigated two of the main problems with radiolabelled antibody imaging, the formation of circulating immune complexes (I.C.) and the non specific binding of radiolabel to the antibody molecule. Patients undergoing immunoscintigraphy with 111In labelled monoclonal antibody ICR2 were divided into three groups who received either the radiolabelled antibody alone (control, n = 12), the radiolabelled antibody which was incubated with the chelating agent diethylene triamine pentacetic acid (DTPA) prior to size exclusion chromatography (n = 6) or whose injectate was treated with DTPA and cold MAb administered intravenously prior to radiolabelled MAb administration (n = 6). Radiolabelled antibody uptake in abdominal organs was measured by region of interest analysis using a gamma camera with online computer and that in tumour and normal tissues by gamma well counting of biopsies. Circulating antigen and immune complex was measured by high pressure liquid chromatography (HPLC). The sensitivity of tumour imaging and the tumour uptake of radiolabelled antibody was not significantly different between the groups. Patients with high circulating antigen levels developed high levels of circulating immune complex but also had high tumour uptakes of radiolabelled antibody. Administration of cold MAb increased the splenic, but did not effect the tumour uptake of radiolabelled antibody and only minimally reduced levels of circulating immune complex. Chelate administration reduced the urinary excretion of radioactivity but increased the liver uptake of radioactivity. These results have shown that successful antibody imaging can be carried out despite high levels of circulating antigen, that large doses of unlabelled antibody are required to prevent immune complex formation and that removal of non specifically bound 111In does not reduce the liver uptake of radioactivity. PMID- 1931606 TI - In vivo 31P nuclear magnetic resonance spectroscopy of experimental murine tumours and human tumour xenografts: effects of blood flow modification. AB - The effect of hydralazine on tumours appears to vary depending on tumour type. Blood flow and radiation sensitivity decrease more in murine tumours than human tumour xenografts. In this study a comparison between various tumour types has been made using in vivo 31P nuclear magnetic resonance spectroscopy (NMRS) to follow the metabolic responses occurring after clamping or intravenous administration of hydralazine (5 mg kg-1). Large increases in the Pi/total phosphate ratio were found with the murine sarcomas, KHT and RIF-1 implanted into C3H/He mice. However little or no effect was seen for the two human xenografted tumours, HX118 and HT29 implanted in MFI nu/nu/01a mice. An intermediate response was observed for KHT tumours grown in nu/nu mice. All tumours showed a large response to clamping. The anaesthetic Hypnorm/Hypnovel has a great influence on the response of the tumour metabolism to hydralazine appearing to both prolong and increase the changes induced. There is evidence to support the theory that the changes in 31P spectra are related to the oxygen status of the tumours. PMID- 1931607 TI - A correlation between nuclear supercoiling and the response of patients with bladder cancer to radiotherapy. AB - Single cell tumour suspensions were prepared from biopsy and urine samples from 28 patients with muscle invasive transitional cell carcinoma of the bladder. Nuclear extracts (nucleoids) containing intact chromatin were isolated from these cells and the condensation of DNA supercoils measured by the light scattered from individual nucleoids within a flow cytometer. Exposure of these nucleoids to 10 micrograms ml-1 ethidium bromide produced 78.9% increase in light scatter compared to those treated with 50 micrograms ml-1. This finding is consistent with the known effect of ethidium bromide on DNA supercoiling and confirms that the light scatter signal is responding to changes at this level of DNA organisation. Cell samples were also exposed to 12 Gy of gamma radiation and the effect on nucleoid light scatter recorded. Of the patients studied prior to radiotherapy, those with persistent disease 3 months after treatment generated an increase in nucleoid light scatter of + 9.35 +/- 4.8% after 12 Gy irradiation, of these, 2/14 produced nucleoids that relaxed by more than 10% compared to controls. Those patients with no evidence of disease after radiotherapy gave an increase in nucleoid light scatter after in vitro irradiation of + 19.3 +/- 4.5% of which 10/14 (71%) relaxed by more than 10%. It is proposed that the increased relaxation within the supercoiled DNA from patients whose tumours were undetectable 3 months after therapy, is related to the inherent radiosensitivity of these tumour cells. Such a difference in nucleoid response within tumour cells from patients that responded to radiation may arise due to a decreased affinity of DNA loops for the nuclear matrix. This structural change, at a site associated with the initiation of DNA synthesis, may affect the ability of cells to continue successful cell division after radiation damage. PMID- 1931608 TI - Histamine, leukotriene C4 and interleukin-2 increase antibody uptake into a human carcinoma xenograft model. AB - Systemically administered radiolabelled anti-tumour antibody is ineffective in treating the majority of patients with liver metastasis from colorectal carcinoma. We have assessed whether agents which increase capillary permeability can increase tumour uptake of antibody isotope conjugate. We developed a xenograft model of colorectal carcinoma using an antibody directed against carcinoembryonic antigen (CEA). Tumours were grown subcutaneously in the hind limbs of athymic rats to derive their circulation from the femoral artery. Cannulae were placed in the common iliac artery and iliolumbar vein. Antibody was delivered systemically, regionally and regionally with histamine, leukotriene C4 and interleukin-2. Regionally administered anti-CEA antibody resulted in a significantly greater (P = 0.004) tumour to normal tissue ratio (1.66, s.d. = 0.68) compared to systematically administered antibody (1.25, s.d. = 0.73). The addition of vasoactive drugs produced an approximately 3-fold increase with an increase to a mean tumour:liver ratio of 3.24 (s.d. = 1.39) for histamine (P less than 0.001 compared to systemic delivery), 3.21 (s.d. = 1.13, P less than 0.001) for leukotriene C4 and 3.80 (s.d. = 1.53, P less than 0.001) for interleukin-2. The addition of histamine significantly (P = 0.004) increased the mean tumour to liver ratio (1.73, s.d. = 0.44) of non-specific antibody uptake compared with either systemic (1.12, s.d. = 0.24) or regional delivery (1.25, s.d. = 0.54) of non-specific antibody alone. Increasing tumour capillary permeability can produce a significant clinically useful increase in tumour uptake of antibody-isotope conjugate. PMID- 1931609 TI - The detection of phthalocyanine fluorescence in normal rat bladder wall using sensitive digital imaging microscopy. AB - The ability to detect photosensitisers in tissue at a microscopical level is important when studying photodynamic therapy (PDT) in both normal and malignant tissue. We have studied the fluorescence distribution of aluminium sulphonated phthalocyanine (A1SPc) in the normal rat bladder using a cooled CCD (charge coupled device) imaging system with computerised image processing. This system makes it possible to carry out a quantitative assessment of photosensitiser fluorescence in the various layers of the bladder wall. The highest fluorescence intensities were obtained within 1 h of intravenous administration but there was little selectivity of uptake between layers. A1SPc was eliminated from the deeper muscle layers more quickly than from the superficial layers of the bladder wall so that by 24 h a 4:1 ratio of fluorescence intensity was apparent which persisted at least until 72 h, although the absolute amount of photosensitiser declined. Following irradiation by red light (675 nm), photobleaching of the sensitiser in the deeper layers further increased this ratio. Direct absorption of A1SPc by the bladder wall following intravesical administration proved unreliable. PMID- 1931610 TI - Pyridinium crosslinks as markers of bone resorption in patients with breast cancer. AB - Collagen breakdown, and thus bone resorption, can now be assessed by measuring the urinary excretion of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd). In a pilot study we measured Pyd and Dpd in 20 patients with breast cancer, ten with known bone metastases and ten with no recognised metastases in bone or elsewhere after 1 year's subsequent follow up. Eight out of the ten patients with metastases had crosslink excretion values higher than the reference interval, but so did some patients without known metastatic disease. For both crosslinks there was a clear correlation with serum alkaline phosphatase activity measured at about the same time. We consider that measurement of urinary collagen crosslink assays may have a place in the early detection of metastatic spread to bone. PMID- 1931611 TI - Endocrine, pharmacokinetic and clinical studies of the aromatase inhibitor 3 ethyl-3-(4-pyridyl)piperidine-2,6-dione ('pyridoglutethimide') in postmenopausal breast cancer patients. AB - The aromatase inhibitor, 'pyridoglutethimide' (PyG), has been shown previously to suppress serum oestrogen levels in postmenopausal breast cancer patients and to achieve clinical responses at a dose of 500 mg twice daily (b.d.). This report gives the results of a detailed pharmacokinetic and endocrine study of PyG in ten patients. Four doses were tested at intervals of 2 weeks in the following order: 200 mg b.d., 400 mg b.d., 800 mg b.d., 1200 mg b.d. Concentration-time profiles of serum levels of PyG were curvilinear in all patients probably reflecting a saturation of metabolic enzymes. During repeat-dosing metabolism was enhanced approximately 2-fold. Plasma levels of oestradiol were significantly suppressed by the lowest dose of PyG. Although higher doses appeared to achieve greater suppression this was not statistically significant in this small group of patients. There were no significant effects at any dose on the serum levels of cortisol, aldosterone, luteinising hormone, follicle stimulating hormone, prolactin, sex hormone binding globulin or thyroid stimulating hormone. There was a dose-related increase in 17 alpha-hydroxyprogesterone levels and a dose-related decrease in levels of dehydroepiandrosterone sulphate (DHAS). The androgens DHA, testosterone and androstenedione also were significantly suppressed with at least one of the doses of PyG. Synacthen tests did not support these changes being a result of inhibition of 17,20 lyase. It is possible that they are due to enhanced clearance of DHAS. Two patients experienced no toxicity throughout the study, whilst a total of four patients were withdrawn because of side-effects: one at 400 mg b.d., two at 800 mg b.d., and one at 1200 mg b.d. The most frequent side effects were nausea and lethargy. One patient showed an objective response to treatment. PMID- 1931612 TI - Elevated serum levels of Dupan-2 in pancreatic cancer patients negative for Lewis blood group phenotype. AB - CA19-9, a serum marker for pancreatic cancer, gives false-negative results in patients who are negative for the Lewis blood group phenotype. To determine whether other markers may compensate for this drawback, serum levels of CA50, Span-1, sialyl SSEA-1 and Dupan-2 were assayed and compared with those of CA19-9 in 207 normal subjects and in 200 patients with pancreatic carcinoma whose Lewis blood group phenotypes were confirmed. In normal subjects with the Lewis negative phenotype, the serum levels of CA50 and Span-1, as well as CA19-9, were significantly low, whereas those of sialyl SSEA-1 were independent of the Lewis blood group phenotype. Serum levels of Dupan-2 were significantly higher in normal subjects with the Le (a-b-) phenotype as compared with those with Le(a b+). The sensitivity for pancreatic carcinoma was 81% for CA19-9, 84% for CA50, 82% for Span-1, 51% for sialyl SSEA-1 and 63% for Dupan-2. Among the 39 CA19-9 negative patients, 13 were determined as being Lewis negative by the serum dot ELISA technique. Although the positive rates were essentially comparable when each marker was combined with CA19-9, a highly elevated serum level of Dupan-2, which strongly suggested the presence of malignancy, was most frequently encountered in 39 patients who were not diagnosed by CA19-9 assay, especially those with Lewis negative blood groups. With regard to the three other markers, we found few patients with a highly elevated serum level in either the Lewis negative or -positive groups. We conclude that Dupan-2 tended to be elevated in patients with pancreatic cancer who were negative for the Lewis blood group phenotype. PMID- 1931613 TI - Deoxycoformycin in the treatment of mature T-cell leukaemias. AB - We describe the results of treatment with 2'-deoxycoformycin (DCF) in 68 patients with post-thymic (mature) T-cell malignancies. These included: prolymphocytic leukaemia (T-PLL), 31, HTLV-1 + adult T-cell leukaemia/lymphoma (ATLL), 20, cutaneous T-cell lymphoma (CTCL), comprising mycosis fungoides and Sezary syndrome, 13, and large granular lymphocytic leukaemia, four. Two-thirds of patients were refractory to previous therapy, which included four drug combinations. DCF was given intravenously at 4 mg m-2 weekly for the first 4 weeks and then every 2 weeks until maximal response. Toxicity was very low with only one death resulting from prolonged neutropenia. Overall response rates, partial (PR) and complete. (CR), were 38%, with variations according to diagnosis. Best responses, 54%, were seen in CTCL but limited to Sezary patients, one CR, six PR, whilst none of the mycosis fungoides responded. Responses in T PLL were recorded in 48% including three CR (of 8-12 months' duration unmaintained) and 12 PR. Fifteen per cent of responses were seen in ATLL. The only ATLL responders - two CR, one PR - were those patients who received combination chemotherapy prior to DCF, with reduction of tumour bulk but short of PR. When results were analysed according to membrane phenotypes it was apparent that responses were seen mainly in cases with CD4+, CD8- T cells -22 of 47 (47%) contrasting with only three of 19 (16%) with other T-cell phenotypes. We conclude that DCF is a useful therapy for the treatment of T-cell leukaemias, in particular Sezary syndrome and T-PLL, and should play a part in strategies to improve the natural history of this group of lymphoid malignancies. PMID- 1931614 TI - Epidermal growth factor receptors (EGFR) in human ovarian cancer. AB - Epidermal growth factor receptor can be used as a biological marker in tumours. We examined 199 samples from 150 patients with ovarian cancer first by using a single point screen, then by full Scatchard analysis, over a concentration range between 0.086-16.6 nM. Taking as positive those samples which showed a 20% difference between total binding and non specific binding, the EGFR was present in 39.7% of samples ranging from 36.4% in those tumours which were classified as being mucinous to 47.7% in the undifferentiated group. Thirty-six samples had a low affinity component (Kd greater than 1 nM), 27 had a high affinity component (Kd less than 1 nM) and 16 had both high and low affinity components to the EGFR. There was no statistical difference between degree of differentiation of the tumour and the presence of the EGFR nor between stage of the disease and EGFR presence. PMID- 1931615 TI - Tumour localisation with a radioactively labelled reshaped human monoclonal antibody. AB - A genetically reshaped human IgG1 monoclonal antibody (Hu2PLAP) with anti-tumour specificity, was radiolabelled with Indium-111 by chelation with a new macrocyclic compound (DOTA) which allows the production of stable radioimmunoconjugates for in vivo application. This was used to image seven patients with malignant disease, of whom two had been previously exposed to mouse monoclonal antibodies and had developed human anti-mouse antibodies (HAMA). Successful tumour localisation was seen in the four patients with active disease and antigen positive tumours. No patient showed any antibody responses against Hu2PLAP, but three out of six patients tested showed an immune response against the macrocycle DOTA. Reshaped human monoclonal antibodies with anti-tumour specificity may facilitate repeated administrations of radioactive antibodies, thus allowing new possibilities, both in the diagnosis and treatment of cancer. PMID- 1931616 TI - Thyroid dysfunction can predict response to immunotherapy with interleukin-2 and interferon-2 alpha. AB - Thyroid dysfunction is a well-recognised side-effect of treatment with interleukin-2 (IL2). We assessed the correlation between the development of abnormal thyroid function and tumour response in 13 patients receiving IL2 and interferon-2 alpha (IFN2 alpha) for advanced malignancy. Seven patients had normal thyroid function during treatment, and all of these patients have since died of progressive disease. Of six patients who did develop thyroid dysfunction during treatment, one patient has died of progressive disease. However, statistically we were unable to confirm a definite correlation between the development of thyroid dysfunction and survival in this small group of patients. PMID- 1931617 TI - The pattern of risk factors for breast cancer in a southern France population. Interest for a stratified analysis by age at diagnosis. AB - A hospital-based case-control study was conducted over 4 years in Southern France to assess the pattern of established risk factors for breast cancer and to examine its variation according to age at diagnosis. Cases studied (450) were women admitted to the Montpellier Cancer Institute, with histologically confirmed primary breast carcinoma. Controls (576) were patients from a nearby hospital admitted in the early stages of a neurological or mild psychological diseases and from a clinic for general surgery. Any patient with malignant tumours, chronic and cardiovascular diseases were excluded. The total population globally showed the commonly reported pattern for these risk factors. When stratified by age, the reproductive factors occurring early in life (menarche, first full term pregnancy) were shown to be significant risk factors only in the youngest group of patients and do not seem to influence risk in older women, for whom risk factors are those occurring later in life (menopause, obesity). This suggests a complex involvement of the reproductive and sociodemographic features with the various stages of the 'natural history' of breast cancer. PMID- 1931618 TI - Relationship between cathepsin D, urokinase, and plasminogen activator inhibitors in malignant vs benign breast tumours. AB - The concentrations of cathepsin D (Cath D), urokinase (uPA) and two plasminogen activator inhibitors (PAI-1 and PAI-2) were analysed in the cytosols of 130 human mammary tumours (43 benign tumours and 87 primary and unilateral breast carcinomas). uPA, PAI-1 and PAI-2 levels were measured by antigenic immunoassays and Cath D by immunoradiometric assay. The median levels of the four parameters were significantly higher in the malignant tumours than in the benign ones. Cath D and uPA increases were 4-fold and 5-fold respectively. PAI-1 and PAI-2 increases were much more important, 74-fold and 29-fold respectively. In malignant tumours, median levels of Cath D and uPA did not vary according to classical prognostic factors (histologic grade, presence or absence of axillary lymph nodes, steroid receptors, UICC stage, tumour size, age, and menopausal status). However, PAI-1 decreased in ER+ and PR+ tumours and PAI-2 increased in menopausal women's tumours. When Cath D, uPA, PAI-1 and PAI-2 levels in malignant tumours were compared, positive correlations were found for all combinations. The implication of plasminogen activator inhibitors in the phenomenon was surprising and merits further investigation using tools other than global antigen measurements in tumours. PMID- 1931619 TI - Involved field radiotherapy or chemotherapy in the management of stage I nodal intermediate grade non-Hodgkin's lymphoma. AB - Early stage intermediate grade non-Hodgkin's lymphoma (NHL) is frequently treated with chemotherapy alone or in conjunction with radiotherapy. We have managed clinical Stage I nodal, intermediate grade NHL with involved field radiotherapy alone for non-bulky (less than 5 cm post-surgery) disease or combination chemotherapy alone for more bulky disease. Forty-three patients were treated between 1978 and 1989. Of the 30 patients with non-bulky disease treated with radiotherapy, 29 (97%) achieved complete remission (CR). Thirteen (42%) patients relapsed after radiotherapy and ten of these achieved a further CR (durable in eight) following salvage chemotherapy. Eleven patients with bulky disease received combination chemotherapy with nine (82%) attaining CR (durable in eight). Two patients with bulky disease received radiotherapy-both achieved CR, but have relapsed and died of lymphoma. Overall actuarial 5 year survival for the total group is 77% with a median follow-up of 30 months (range 3-119 months). The 5 year actuarial survival for the 30 patients with non-bulky disease treated with radiotherapy is 86% at a median follow-up of 39 months (range 8-119 months). The 4 year actuarial survival of the 11 patients treated with chemotherapy is 60% with a median follow-up of 25 months (range 3-55 months). We conclude that involved field radiotherapy alone is efficacious for clinical stage I patients with non-bulky nodal intermediate grade NHL and that patients relapsing after radiotherapy are adequately salvaged by chemotherapy. Patients with bulky disease have an inferior survival and should receive combination chemotherapy. PMID- 1931620 TI - Long term prognosis and quality of life following intensive care for life threatening complications of haematological malignancy. AB - Ninety-two consecutive adult patients admitted with acute life-threatening complications of haematological malignancy were studied to determine long term outcome. The quality of life was evaluated in seven long term survivors who are currently alive more than 1 year after hospital discharge using three validated methods: the Nottingham Health Profile, the Hospital Anxiety and Depression Scale and the Perceived Quality of Life Scale. Patients were also asked whether they had returned to work, whether their daily activities were limited and whether they would be willing to undergo intensive care again under the same circumstances. The in-hospital mortality rate was 77%. Median duration of long term survival was 23 months (range 6 weeks to 8 years). Long term survival did not appear to be related to either the aetiology or the severity of the acute illness, but seemed to be determined solely by the nature and progress of the underlying malignancy. The quality of life of six of the seven long term survivors is good, while that of the other is acceptable. None of the patients reported any increased limitation of their daily activities, five had returned to full time employment and all seven stated that they would be willing to undergo intensive care again under the same circumstances. PMID- 1931621 TI - Correlation of clinical pigmentary characteristics with histopathologically confirmed dysplastic nevi in nonfamilial melanoma patients. Studies of melanocytic nevi IX. AB - The dysplastic melanocytic nevus (DMN) is the key clinical marker for the familial dysplastic nevus syndrome and has also been associated with high risk for non-familial melanoma. Characterisations of DMN itself have been qualitative and on a case-by-case basis. In this study, we provided clinical and histological characterisations for each of 150 pigmented lesions from 150 patients with prior malignant melanoma. The steps involved in the study were as follows: (1) The two to four clinicians characterised pigmented lesions on each of 150 patients, and the lesion closest in characteristics to an atypical nevus was quantitatively described based on size, border characteristics and colour characteristics; (2) The lesion was then removed and independently quantified by a single dermatopathologist without knowledge of the clinical features; (3) We computed the correlation between each of the clinical variables and each of the histologic features for each of the 150 patients. Histologic diagnosis of dysplastic nevus was strongly associated with total number of palpable arm nevi, total number of any arm nevi, total number of nevi on the body of any type, and total number of clinically atypical nevi on the body (correlation coefficients 23.2% to 30.4% with P less than 0.01 in each instance). There were also strong correlations between the counts of numbers of nevi and certain types of architectural histologic features, including fusion (bridging of junctional nests), lymphocyte response and fibroplasia of the papillary dermis. Histologic evaluation of solar elastosis was negatively correlated with total numbers of nevi and total number of clinically atypical nevi (P less than 0.01). Freckling on forearm and on shoulders showed no significant positive or negative correlations with any of the histologic features nor with overall diagnosis of dysplastic nevus. We conclude that observations regarding total numbers of nevi (either normal or clinically atypical nevi) are correlated with nuclear and architectural histologic dysplasia on biopsy of the most atypical pigmented lesions. PMID- 1931622 TI - DNA ploidy in primary testicular cancer. AB - The DNA stemline ploidy was measured by flow cytometry (FCM) in 129 samples from paraffin-embedded primary testicular tumours (61 seminomas, 68 non-seminomas). Only one DNA stemline was found in 38 seminomas and 44 non-seminomas. Two seminomas and one non-seminoma were DNA diploid, the other tumours being non diploid. Twenty-three seminomas and 24 non-seminomas displayed two or three DNA stemlines. The median minimal DNA index (DI) of all seminomas was significantly higher than that of all non-seminomas (1.58 vs 1.43; P: 0.008). Three seminomas removed from two monozygotic twins within 1 week had DIs of 1.66, 1.56 and 1.59. In this limited series there was no association between DNA ploidy of the primary tumour and the metastatic status for either seminomas or non-seminomas. The results support the pathogenetic model stating that at least some (if not all) non-seminomas develop from a seminoma by additional chromosomal aberration. The clinical relevance of DNA stemline ploidy has to be further evaluated in larger series. PMID- 1931623 TI - Is there an increased risk of breast cancer in women who have had a breast cyst aspirated? AB - A consecutive series of 644 women who presented with breast nodularity between 1976 and 1982 have been followed up to determine their rate of subsequent breast cancer. Fifteen women have developed breast cancer, 14 of these were among 352 women with an aspirated cyst (relative risk 4.4). Women with multiple cysts had the highest risk and women with breast nodularity had no excess risk. Review of histology specimens from those women who had undergone biopsy showed an excess of florid epithelial hyperplasia in women who subsequently developed breast cancer and women with multiple aspirated cysts were more likely to have florid epithelial hyperplasia. Multiple cysts are clinical markers of histological breast proliferation and women who have had multiple breast cysts aspirated have an increased risk of breast cancer and should be advised to practice regular self examination. PMID- 1931624 TI - Decrease in cholesterol levels during the immunotherapy of cancer with interleukin-2. AB - IL-2, in addition to its immunomodulating and antitumour properties, induces important systemic actions, including cardiovascular, neuroendocrine and metabolic effects. The present study was carried out to evaluate IL-2 effects on cholesterol metabolism. The study included 14 advanced cancer patients (renal carcinoma: ten; colon carcinoma: four), who received IL-2 subcutaneously at a dose of 1.8 x 10(6) IU ml-2 twice daily for 5 days/week for 6 weeks. Venous blood samples were collected 7 days before, on days 0, 3, 7, 14, 21, 42 of IL-2 therapy, and on days 14 and 28 of the rest-period. IL-2 induced a rapid and evident decrease in cholesterol levels, with a normalisation of its concentrations within 7 days in 10/10 hypercholesterolemic patients. The lowest mean levels of cholesterol were reached within the first 2 weeks; after that they still slowly increased. LDL-/HDL-cholesterol ratio was significantly reduced by IL-2 therapy. Cholesterol fall was associated with a marked increase in conjugated biliary acid levels. Finally, triglyceride values increased during IL 2 therapy, but not in a significant manner. These results, by showing that IL-2 exerts an evident and very rapid cholesterol-lowering activity, would represent a further demonstration of the physiological importance of cytokines in the control of cholesterol metabolism. PMID- 1931626 TI - Breast cancer screening as public health policy in Finland. AB - A nationwide mammographic screening for breast cancer was started in Finland in 1987. During the first 2 years of the organised screening programme, 126,000 women were invited. Most of them (103,000) belonged to the birth year cohort in the 50-59 years' age groups. Among the 112,000 screenees, 418 cancers (0.4%) were found. Specificity of the test was about 96%. The screening prevalence was 2.4 times the annual incidence and a minimum estimate for the detection rate among those invited was 1.6 times that among those not invited. These estimates indicate a relatively low test and programme sensitivity. The final effectiveness of a public health policy cannot be predicted on the basis of limited preventive trials, and there is need to evaluate also a public health policy by experimental means. PMID- 1931625 TI - The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. AB - We have investigated the incidence of Gorlin syndrome (GS) in patients with the childhood brain tumour, medulloblastoma. One hundred and seventy-three consecutive cases of medulloblastoma in the North-West Regional Health Authority between 1954 and 1989 (Manchester Regional Health Board before 1974) were studied. After review of case notes, X-rays and health surveys only 2/173 cases had evidence supporting a diagnosis of GS. A further case at 50% risk of GS died of a brain tumour aged 4 years. The incidence of GS in medulloblastoma is, therefore, probably between 1-2%. A population based study of GS in the region started in 1983 was used to assess the incidence of medulloblastoma in GS, which was found to be between 3-5%. This figure is lower than previous estimates, but this is the first population based study undertaken. In view of the early age of onset in GS (mean 2 years) children presenting with medulloblastoma, especially under 5 years, should be examined for signs of the syndrome. Those at high risk of developing multiple invasive basal cell carcinomata will then be identified. PMID- 1931627 TI - Cathepsin D and epidermal growth factor in human breast cyst fluid. AB - Cathespin D (Cath D) is a proteolytic enzyme secreted by human breast cancer cells with a growth promoting activity in vitro. In the present study, we measured Cath D and Epidermal Growth Factor/alpha Transforming Growth Factor (EGF/alpha-TGF) concentrations in the breast cyst fluid (BCF) of 43 patients with gross cystic disease of the breast. Both Cath D (median 2.45 pmoles mg-1 protein; range 0-4.84 vs 0.98 pmoles mg-1 protein; range 0-3.11) and EGF/alpha-TGF (28.71 ng mg-1 protein; range 7.05-50.63 vs 10.83 ng mg-1 protein; range 0.06-30.55) levels were higher in BCF of apocrine than flattened cysts (P less than 0.0005 and P less than 0.01, respectively). Premenopausal patients showed higher concentrations of Cath D (P less than 0.05) and EGF/alpha-TGF (P less than 0.05) than postmenopausal patients. A positive correlation was obtained between intracystic concentrations of Cath D and EGF/alpha-TGF (P less than 0.00001). The higher levels of Cath-D and EGF/alpha-TGF found in apocrine cysts could provide an explanation for the increased risk of subsequent breast cancer in women with this type of cyst. PMID- 1931628 TI - A prospective randomised trial of radiation with or without oral and intravesical misonidazole for bladder cancer. AB - Patients with T2 grade 3 and T3 bladder cancer were randomised to be treated with radiation alone (NO MISO) or with radiation and misonidazole (PLUS MISO). Patients in both groups initially received 40 Gy in 2 Gy fractions (5/week). Patients in the NO MISO arm received a further 20 Gy in 2 Gy fractions (5/week). Patients in the PLUS MISO arm received a further 12 Gy in 6 Gy fractions (1/week). MISO was administered orally (3.0 g m-2) and intravesically (1.0 g in 35 ml of solvent) 4 h and 2 h respectively prior to each fraction of 6 Gy. Fifty eight patients were randomized of whom 53 are evaluable. There is a minimum follow-up of 5 years in the surviving patients. In the NO MISO and PLUS MISO arms, the complete response rate at cystoscopy at 6 months was 63% and 69%, the 5 year survival rate was 41% and 48% and the 5-year local control rate with bladder preservation was 46% and 36% respectively (censored for death from metastases while locally clear). These differences are not statistically significant. Two patients had grade 3 RTOG late bowel complications. Both patients were in the PLUS MISO arm, had undergone salvage cystectomy and subsequently required colostomies for bowel obstruction for a 5-year late complication rate (RTOG grade 3) of 9%. In addition, two patients in the PLUS MISO arm developed wound sepsis post cystectomy. We were not able to demonstrate improved results from the use of oral and intravesical MISO in this study. The number of patients entered are relatively low and large differences would have been required to be detected with a power of 0.80. The use of an unconventional radiation fractionation schedule may have resulted in increased bowel morbidity in patients in the PLUS MISO arm who subsequently underwent cystectomy. PMID- 1931629 TI - Categorising continuous variables. PMID- 1931630 TI - NHS Trusts. Manager on the move. Interview by John Naish. PMID- 1931631 TI - Health politics: rescuing the NHS. Interview by Jean Gray. PMID- 1931632 TI - Counselling: professional BACUP. PMID- 1931633 TI - Scholarships: a living memorial. PMID- 1931634 TI - Stoma care: managing high-output fistulas. PMID- 1931636 TI - Practice nurses: at the crossroads? PMID- 1931635 TI - An application of learning theory. PMID- 1931637 TI - The normal ageing process reviewed. PMID- 1931638 TI - Top of the class. PMID- 1931639 TI - A profession caring. PMID- 1931640 TI - Substance abuse: proscribed or prescribed? PMID- 1931641 TI - Northern Ireland. Taking up the challenge. PMID- 1931643 TI - Northern Ireland. A strategy for education. PMID- 1931642 TI - Northern Ireland. A strategy for practice. PMID- 1931644 TI - Northern Ireland. A strategy for leadership. PMID- 1931645 TI - Northern Ireland. A strategy for research. PMID- 1931646 TI - Pay: time for a fair deal. PMID- 1931647 TI - RCN nursing update: a project comes alive. PMID- 1931648 TI - Northern Ireland focus. Computers in the curriculum. PMID- 1931649 TI - Health status in rheumatic disease. PMID- 1931650 TI - Nursing matters: caring for a victim of rape. PMID- 1931651 TI - Job mobility among nurse teachers. PMID- 1931652 TI - The enigma of puerperal psychosis. PMID- 1931653 TI - An evaluation tool for primary nursing. PMID- 1931654 TI - The future re: wards. PMID- 1931655 TI - Encompassing the reforms. PMID- 1931656 TI - The Nat Health files: management comes clean. PMID- 1931657 TI - AIDS focus. A wider perspective in symptom relief. PMID- 1931658 TI - AIDS focus. Sexuality--a topical issue for nursing. PMID- 1931659 TI - Day surgery: accommodating care. PMID- 1931660 TI - Continuing education: a framework for updating. PMID- 1931661 TI - Diabetic home care. PMID- 1931662 TI - Care of the dying: dying East, dying West. PMID- 1931663 TI - Chemical burns of the eye. PMID- 1931664 TI - Guidelines for the role of preceptor. PMID- 1931665 TI - Psychiatry: attitudes to working in special hospitals. PMID- 1931666 TI - Politics and ethics in nursing research. PMID- 1931667 TI - Tobacco advertising. PMID- 1931668 TI - NHS reforms: trading health for wealth. PMID- 1931669 TI - Learning at their laptops. PMID- 1931670 TI - Carry on matron? PMID- 1931671 TI - Working parents: outclassed and uneducated. PMID- 1931673 TI - [Reintegration into the profession--report on the first reintegration course in Krefeld]. PMID- 1931674 TI - [Day nurseries are dangerous]. PMID- 1931672 TI - Work-injured nurses: uplifting experience? PMID- 1931675 TI - [Nursing and care of children with bronchial asthma and mucoviscidosis]. PMID- 1931676 TI - [Gerty Theresa Cori (1896-1957)]. PMID- 1931677 TI - [Early diagnosis of cerebral paresis]. PMID- 1931678 TI - [European charter "Environment and Health"]. PMID- 1931680 TI - [Practical instruction--a must, not a necessary evil]. PMID- 1931679 TI - [Echocardiography--its value in cardiological diagnosis]. PMID- 1931681 TI - [Place of learning: pediatric hospital]. PMID- 1931682 TI - [Professional activities of a pediatric nurse]. PMID- 1931683 TI - [Pediatric-surgical treatment measures after burns and scalds]. PMID- 1931684 TI - [Child neglect--experiences from home nursing]. PMID- 1931685 TI - [Education of diabetic children, adolescents and their parents]. PMID- 1931686 TI - [The role of the sick child in practical training]. PMID- 1931688 TI - [Planning the instruction in education]. PMID- 1931687 TI - [Educational engagement in a therapeutic-educational nursery--report by a trainee]. PMID- 1931689 TI - [The nursing legislation is also used in the new federal counties]. PMID- 1931690 TI - [Letter to the pediatric nurses]. PMID- 1931691 TI - [Wilhelm Stoeltzner (1872-1954)]. PMID- 1931692 TI - [Mucoviscidosis]. PMID- 1931693 TI - [Nursing report from England]. PMID- 1931694 TI - [Hygienic measures in infusion therapy]. PMID- 1931695 TI - [Child abuse--first contact with the child and its parents in the pediatric hospital]. PMID- 1931696 TI - [Selma Meyer (1881-1958), the first female professor of pediatrics]. PMID- 1931697 TI - [Children's feet grow fast--faster than the parents think]. PMID- 1931698 TI - [Pictures of pediatric diseases from former times]. PMID- 1931699 TI - [Viral skin diseases in children]. PMID- 1931700 TI - [Report of experiences of a pediatric nurse as a mother]. PMID- 1931701 TI - [The physician's obligation to disclose the truth in cases of urgent further diagnosis]. PMID- 1931702 TI - Possible mechanism of action of interferon alpha in chronic B-cell malignancies. AB - Recent evidence suggests that tumour necrosis factor alpha (TNF) is an autocrine growth factor for the chronic B-cell malignancies hairy cell leukaemia (HCL) and some cases of B-chronic lymphocytic leukaemia (B-CLL). Incubation with TNF in vitro has been shown to increase viability, DNA synthesis and the expression of the protooncogenes myc, fos and jun in the tumour cells from these patients. TNF in vitro also increases expression of TNF-mRNA, suggesting the existence of an autocrine growth loop for TNF in these cells. Current experiments are compatible with the hypothesis that interferon alpha (IFN) interferes with this autocrine growth loop in HCL and B-CLL by stimulating degradation of messenger RNAs (mRNAs) for a number of cytokines including that of TNF. This RNA degradation may be mediated through induction of the enzyme 2,5 oligo-A synthetase with consequent increased synthesis of 2,5 oligo-A which is known to stimulate the activity of a latent ribonuclease capable of degrading cytokine mRNAs. Circulating tumour derived TNF may also contribute to the pancytopenia in HCL and B-CLL. Whether cytokine autocrine growth loops are important in other B-cell malignancies, e.g. myeloma and non-Hodgkin's lymphoma, and subject to IFN-stimulated breakdown needs further study. PMID- 1931703 TI - Treatment of multiple myeloma with interferon alpha: the Scandinavian experience. AB - IFN alpha is a biologic therapeutic agent with documented antitumoral effect in multiple myeloma. 15% of previously untreated myeloma patients achieve a clinical response to IFN alpha alone with a possible dose-response relationship. A particularly good effect is noted in IgA myelomas treated with natural IFN alpha. A randomized study was started in April 1986 comparing melphalan/prednisone (MP) therapy with MP plus natural IFN alpha (MP/IFN) in untreated patients with multiple myeloma stages II and III. 220 patients had entered the study by autumn 1989. An interim report is given here. The response frequency was 48% in the MP group and 66% in the MP/IFN group (P less than 0.02). Stage II patients responded better to MP/IFN (76%) than to MP alone (48%) (P less than 0.01). No significant difference was noted for stage III patients. 91% of all IgA myelomas responded to MP/IFN and 52% to MP (P less than 0.01). The difference in response frequency of IgG and BJ myelomas between the two treatment groups was not statistically significant. The observation period is still too short to draw firm conclusions on survival. However, a statistically significant longer response duration time and survival from response (P less than 0.01) was noted for stage II patients. PMID- 1931704 TI - Interferon alpha in lymphoma. AB - A number of studies are currently in progress to evaluate the use of interferon alpha, alone and in combination with conventional chemotherapy in patients with follicular lymphoma. The background to these is reviewed, together with currently available data about the potential role of interferon alpha in cutaneous T cell lymphoma. PMID- 1931705 TI - Interferon alfa-2b therapy in untreated early stage, B-chronic lymphocytic leukaemia patients: one-year follow-up. AB - Recent reports have shown that interferon alpha is effective in B-chronic lymphocytic leukaemia (B-CLL). In a previous study from our unit we obtained a 50% response rate with interferon alfa-2b in B-CLL in early stages. Subsequently, we performed the present study randomizing 34 Binet stage AI, B-CLL patients who were not previously treated (eight controls and 26 who were to receive interferon alfa-2b (IFN alpha-2b) (Intron-A) according to a randomized schedule as follows: 1.5 MU/d in eight patients, 1.5 MU three times a week in 10 patients and 3.0 MU three times a week in eight patients). At 3 months complete response (CR) was obtained in one, partial haematologic response (PHR) in nine and minor haematologic response (MHR) in seven patients with an overall response rate 17/26 or 65%. No bone marrow changes regarding the pattern or degree of infiltration was noticed in any of the responding patients except for the complete responder. Treatment was continued in 15 patients (reduced to two-thirds of the initial dose in the PHR and to one third of the initial dose in the MHR) while in 11 patients it was discontinued because of no response, negative response or toxicity. At 6 months sustained response was observed in 10 patients, while in the remaining five an increase of blood lymphocytes was seen at numbers similar or higher to those noted prior to interferon alfa-2b therapy. Two of the 10 patients in whom blood lymphocytes were still reduced to less than 50% of the pretreatment values, developed gradual lymph node enlargement and therapy had to be discontinued. During the following 6 months the interferon alfa-2b dose was further reduced in all remaining responders to 1.5 MU once or twice a week and their counts remained at the same level as at 6 months of therapy. At 12 months, 18 of our patients were still in stage A while seven had progressed (five to stage B and two to stage C). The overall response after 12 months of therapy was sustained in 8/17 responders. We conclude from our study that interferon alfa-2b is effective in untreated B-CLL patients in early stages and therefore should be investigated in combination with conventional chemotherapy. Clinical trials utilizing interferon alfa-2b and chlorambucil in combination in untreated B-CLL patients are currently in progress in our unit. PMID- 1931706 TI - The molecular pathology of chronic myelogenous leukaemia. AB - The first consistent karyotypic abnormality found to be associated with neoplastic disease was the Philadelphia (Ph) chromosome (Nowell & Hungerford, 1960). Furthermore, the best-studied example of translocation-mediated gene activation occurs in leukaemia patients bearing this abnormality (reviewed by Kurzrock et al, 1988). In these individuals, the Ph translocation (t(9;22)(q34;q11)) results in transposition of the ABL proto-oncogene from chromosome 9q34 to 22q11, where it is fused with part of the BCR gene. It is now known that as a result of the Ph translocation, p160BCR and p145ABL (the normal BCR and ABL gene products) are replaced by p210BCR-ABL. This aberrant protein constitutes the molecular fingerprint of CML. The enhanced tyrosine phosphokinase enzymatic activity (a property possessed by some growth factor receptors and transformation-inducing oncogenes) of p210BCR-ABL implicates a direct role for this molecule in the pathogenesis of CML. Because the Ph translocation is present in the early chronic phase, the union of the BCR and ABL genes is probably involved in the initiation of the leukaemic process. The secondary molecular forces driving progression of CML to blast crisis are however unknown, and may differ from patient to patient. Approximately 10% of CML patients lack a Ph chromosome. One-half of these individuals have bcr rearrangement and express p210BCR-ABL. Ph+ and Ph- bcr+ (p210+) CML are identical and should be treated the same. Molecular follow-up of diploid bcr+ CML patients is essential for detection of persistent malignancy after therapy. The presence of a specific marker--the BCR-ABL message--permits the development of new diagnostic approaches for CML. For instance, detection of a BCR-ABL message with the use of the highly sensitive polymerase chain reaction, a technique capable of detecting up to one leukaemia cell amongst one million normal cells, yields important information about minimal residual disease. Finally, the use of therapy directed against the BCR-ABL product may be a worthwhile strategy which deserves investigation, and may prompt a new era of tumour-specific treatment. PMID- 1931707 TI - Interferon alpha in the therapy of CML. AB - This paper summarizes the experience with interferon alpha (IFN alpha) as single agent therapy and in combination gathered at M.D. Anderson Cancer Center. It also covers some of the laboratory research associated with these clinical studies. PMID- 1931708 TI - Interferon in essential thrombocythaemia. AB - In the present investigation, 20 patients with ET were treated with recombinant interferon alfa-2c (IFN) for up to 4 years. Initially, IFN was administered subcutaneously at a dosage of 6-45 MU/week. The dosage was adjusted according to individual tolerance and response. The median dose during induction was 20 MU/week, 10 MU/week during the remaining first year, 6 MU/week during the second year and 2 MU/week thereafter. 13 patients (65%) achieved complete remission (platelet count less than 440/nl), four patients (20%) had partial remission (greater than 440/nl but a reduction by more than 50% of the initial count). The median platelet count remained steady throughout the 4-year period of treatment, in spite of extreme dose reductions. After withdrawal of IFN, however, platelet counts again increased. The white blood cells showed a marked decrease similar to that of platelet counts, whereas the haemoglobin level remained fairly stable. In the bone marrow, a significant decrease in megakaryocyte density and size could be observed. Concurrently with the improvement of haematological parameters, clinical symptoms improved, but reappeared after withdrawal of IFN. During induction, fever, bone and/or muscle pain, fatigue, lethargy and psychological symptoms were the most prominent side-effects in the majority of patients. In three patients these symptoms led to discontinuation of the treatment. With repeated dose reductions, excellent long-term tolerance was achieved, and during late maintenance treatment the only observed side-effect was an induction of thyroid autoimmunity in three patients. IFN is an effective, well-tolerated alternative in the long-term treatment of symptomatic ET. However, since withdrawal of IFN leads to recurrence of thrombocytosis, continued treatment is to be recommended. PMID- 1931709 TI - Is interferon alpha in cutaneous T-cell lymphoma a treatment of choice? AB - This study was designed to evaluate the therapeutic efficacy and toxicity of recombinant interferon alpha-2a (rIFN alfa-2a) given as initial systemic therapy in untreated mycosis fungoides and/or Sezary's syndrome patients, at a slowly escalating schedule up to the maximal tolerated dose. At the same time this schedule was administered in patients who had relapsed or were refractory to previous treatment; 28 newly diagnosed and 15 previously treated patients entered the study. IFN was given daily with dose escalation from 3 to 18 MU. The last follow-up in June 1990 indicates that 90% of previously untreated patients who obtained a complete remission remain in continuous complete remission after 18 to 40 months and that 75% of previously untreated patients who obtained partial remission remain in partial remission after 20-44 months. The event-free survival projected, calculated using the Kaplan and Meier product limit technique, was 21% of all patients at 54.7 months (40% in the previously untreated groups and 14% in the previously treated group: P = 0.12). In conclusion, interferon is very effective as a single agent in cutaneous T-cell lymphomas. PMID- 1931710 TI - Rational basis for the metabolic modulation of 5-fluorouracil by leucovorin and interferon alpha. AB - Although 5-fluorouracil (FUra) has been the drug of choice for the treatment of patients with advanced colorectal carcinoma, the response rates are in the range of 15% and the median survival times do not exceed 9 months. Interferon alpha (IFN alpha) has limited antitumour activity in this disease. Recent clinical trials have demonstrated that both the response rate and the survival time of patients with advanced colorectal cancer can be significantly improved by the addition of leucovorin (CF) to FUra. In a randomized phase III trial, the median response to FUra and CF was about 30% with a range of 20-55%, dependent on the dose and schedule of administration of CF. Due to multiplicity of mechanisms of action postulated for IFN alpha, the role of IFN alpha in the modulation of the cytotoxicity and therapeutic efficacy of FUra alone and in combination with CF has been evaluated in patients with advanced colorectal cancer and also in a variety of human cell lines in culture, including human colorectal cell lines, HCT-8, human bladder cell line RT-4 and leukaemia CEM cells. The results obtained in patients demonstrated that indeed the antitumour activity of FUra can be improved by the addition of IFN alpha with a response range from 26% to 76%. The initial clinical use of this combination, however, has been limited in some cases by the severe host toxicity. In vitro results demonstrated that: (1) in vitro cytotoxicity potentiation by IFN alpha is cell-type dependent; (2) in these cells where modulation was possible, alpha IFN was used as a low and noncytotoxic doses (10-50 micrograms/ml for 3-5 d exposure), and (3) the cytotoxicity of IFN alpha was dose dependent, indicating a direct antiproliferative cellular effect. PMID- 1931711 TI - Fluorouracil and recombinant interferon alfa-2a in advanced gastrointestinal neoplasms. AB - Based on preclinical studies which demonstrated synergy between recombinant interferon alfa-2a (rIFN alpha-2a) and 5-fluorouracil (5FU), clinical studies have been initiated to investigate this combination. The initial study conducted by investigators from the Albert Einstein Cancer Center reported a response rate of 76% with 13/17 patients with advanced colorectal carcinoma responding. To further evaluate this regimen, two clinical trials have been conducted in previously untreated advanced colorectal carcinoma patients with measurable disease. The regimen consisted of 5FU administered as a continuous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting 1 week after completion of the continuous infusion. rIFN alpha-2a, 9 MU, was administered subcutaneously three times weekly. In The University of Texas M.D. Anderson Cancer Center trial, 15/45 evaluable patients experienced partial response, and one patient achieved a complete response for an overall response rate of 35%. Another trial of this regimen conducted by Memorial Sloan-Kettering has reported a 26% response rate with 9/34 evaluable patients experiencing a partial response. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid or single-agent 5FU may clarify its role in the treatment of advanced colorectal carcinomas. PMID- 1931712 TI - Treatment of advanced malignant melanoma with recombinant interferon alfa-2a in combination with DTIC: long-term follow-up of two phase II studies. AB - The present studies were designed to examine whether treatment of disseminated melanoma with a combination of recombinant interferon alpha (rIFN alpha-2a) and DTIC may provide better results than either agent alone. Two dose levels of rIFN alpha-2a were examined with the same dose and schedule of DTIC administration. In the first study 76 patients were treated with rIFN alpha-2a (3 x 10(6) IU days 1 3, 9 x 10(6) IU days 4-70 then 9 x 10(6) IU TIW) plus DTIC (i.v. 200 mg/m2, escalating to 800 mg/m2 each 21 d) for 6 months or longer or until failure. Responses were seen in 26% of patients overall (7CR, 13PR) with the highest responses being seen in those assessed as having a good prognosis and in patients with skin and/or lung metastases. It was notable that males showed a better response than females and that patients with metastases in lymph nodes showed low responses. Response rates in 30 patients treated with high-dose rIFN alpha-2a (18 x 10(6) IU days 7-70) were not superior to that seen at the lower dose and was accompanied by significant increase in bone marrow toxicity. The duration of responses appeared longer than expected from responses to DTIC alone and four patients remain progression free at periods in excess of 3 years. Failure in nine of the responders was due to the development of brain metastases which emphasizes the need for additional treatment approaches to treat micrometastases at this site. The results of a randomized control study comparing DTIC alone with DTIC plus 'low' dose rIFN alpha-2a are awaited with interest. PMID- 1931713 TI - Interferon alpha therapy of haemangiomas in newborns and infants. PMID- 1931714 TI - Interferon alpha in the treatment of AIDS-related Kaposi's sarcoma. AB - Interferon alpha was one of the first drugs tested for the treatment of patients with AIDS-related Kaposi's sarcoma based on its known antiviral properties and its abilities to modulate immune function and inhibit neoplastic cell proliferation. In vitro studies demonstrated defective production of interferon by blood cells of HIV-infected individuals and suppression of HIV replication by interferons alpha and beta. Interferons have also been shown to inhibit angiogenesis induced by tumour cells or by allogeneic lymphocytes in mice. The efficacy of recombinant interferon alpha for the treatment of AIDS-related Kaposi's sarcoma has been well documented with antitumour responses seen in approximately 30% of all patients treated in single agent efficacy trials with doses of at least 20 MU/m2. In several uncontrolled studies, response of Kaposi's sarcoma to treatment with interferon alpha was associated with longer survival and few opportunistic infections. Tumour response appears to be correlated with an absence of opportunistic infection and with CD4 cell numbers. Several studies using high interferon alpha doses have demonstrated decreases in serum HIV P24 core antigens which appear to be confined to patients whose tumours also regressed. The use of interferon alpha in HIV-infected patients with or without Kaposi's sarcoma have demonstrated in vivo anti-HIV activity. Studies have recently evaluated the tolerance and therapeutic potential of interferon alpha in combination with the reverse transcriptase inhibitor, zidovudine (azidothymidine AZT). Synergistic suppression of HIV replication in vitro has been demonstrated with the combination of interferon alpha and zidovudine. The description of HIV isolates with reduced sensitivity to zidovudine following prolonged treatment, and the finding that interferon alpha, but not zidovudine, prevents HIV expression in chronically infected cell lines, suggests that this combination might be useful in long-term treatment of patients with HIV infection. PMID- 1931715 TI - Interferon alpha in combination with other biologics: the scientific rationale. AB - Interferon alpha (IFN alpha) has widely pleiotropic effects, on both the immune system and tumour cells, and any of these effects might provide the basis for additive or synergistic effects when administered in combination with other biologics. Some of the main sites of action to consider include the ability of IFN alpha to: inhibit the growth of tumour cells; induce differentiation, and/or MHC expression on tumour cells; and stimulate the activation and/or differentiation of natural killer (NK) cells, cytotoxic T lymphocytes, and cytotoxic macrophages. Other biologics with similar sites of action might be expected to provide additional effects when combined with IFN alpha, and factors with other, complementary anti-tumour effects might synergize. Potentially important therapeutic effects have been observed when IFN alpha has been combined with IFN gamma, interleukin 2, tumour necrosis factor, interleukin 1, monoclonal antibodies, and retinoids. The development of therapeutic strategies on the basis of hypotheses as to how IFN alpha might effectively interact with another biologic, coupled with careful assessment of effects on the tumour cells and/or serial monitoring of immunologic parameters, might be expected to lead most expeditiously to successful therapeutic combinations of IFN alpha with other biologics. PMID- 1931716 TI - Interferon in combination with antitumourigenic phenyl derivatives: potentiation of IFN alpha activity in-vitro. AB - Any attempt to eradicate the heterogeneous cell population of a tumour mass would require the use of appropriate combination treatment protocols. The antitumour effects of interferon alpha (IFN alpha) in combination with AS2-1, the hydrolysis product of 3-phenylacetyl-amino-2,6-piperidinedione, were examined using several human tumour cell lines as a model. These included the malignant melanoma A375, adenocarcinoma of the prostate PC3 (hormone-insensitive bone metastasis), and the erythroleukaemia line K562. AS2-1 suppressed tumour growth through non-toxic mechanisms, with 1 mg/ml causing approximately 50% inhibition of the melanoma and prostate tumour cell proliferation. By contrast, primary normal human skin fibroblasts were significantly less sensitive to the antiproliferative effect of AS2-1. Suppression of tumour growth was seen also with AS2-1 treatment of the erythroleukaemia K562; in these cultures the drug also induced dose-dependent differentiation, as indicated by the increased haemoglobin production. Interestingly, addition of low doses of IFN alpha markedly enhanced the antitumour and differentiating effects observed with AS2-1. Treatment with 200 300 IU/ml of IFN (which caused about 20% inhibition of growth) together with 1 mg/ml of AS2-1 resulted in over 80% inhibition of the melanoma and prostate cancer cell proliferation, suggesting a synergistic activity of the two agents. This was substantiated by quantitative analysis of the differentiation induced in K562 erythroleukaemia. It appears, therefore, that IFN alpha and AS2-1 may act through synergistic mechanisms to effectively inhibit tumour growth and promote differentiation in a variety of human malignant cell lines. PMID- 1931717 TI - Clinical experience with the combined use of recombinant interleukin-2 (IL2) and interferon alfa-2a (IFN alpha) in metastatic melanoma. AB - A multicentre study of IL2 and IFN alpha has been performed in 58 patients with metastatic melanoma. The scheme consisted of IL2 3.0 BRMP MU/m2/d as a continuous infusion for 4 d combined with subcutaneous administration of IFN alpha 6 MU/m2/d, day 1 + 4. The cycle was repeated every 2 weeks for a maximum duration of 26 weeks. 54 patients were evaluable for response. One (2%) achieved a complete and 10 (19%) a partial response. 19 (35%) patients were stable and 24 (44%) showed progressive disease. Common side-effects included fever, chills, fatigue, skin rash, anorexia, nausea and diarrhoea. Hypothyroidism was noted in 10% of the patients. These results show that this regimen of IL2 and IFN alpha is active but, in contrast to what could be expected, not superior to IL2 alone possibly due to suboptimal dosing. In an ongoing study in Rotterdam and Nijmegen, a more intense schedule was chosen, consisting of three daily i.v. doses of IL2 4.5 BRMP MU/m2 and IFN alpha 3.0 MU/m2 for 5 d. This regimen is repeated at intervals of 3 weeks for a total of three cycles. Presently, nine patients have been entered. One patient achieved a complete response, four a partial response (overall 56%), three had stable disease and one progressed. Toxicity was severe and treatment was prematurely stopped in five patients: myocardial infarction (one patient), atrial fibrillation (one patient), negative T waves and myocardial hypokinesia (one patient) and psychosis (two patients). This regimen can only be justified if the therapeutic results are superb, which has yet to be awaited. PMID- 1931718 TI - Signal transduction pathway activating interferon-alpha-stimulated gene expression. AB - Interferon-alpha (IFN alpha) causes profound physiological changes following binding to susceptible target cells. These changes, which include induction of an antiviral state, inhibition of cellular proliferation, and modulation of differentiation, require the transcriptional activation of a set of genes. We have characterized the macromolecular components required for this stimulation of gene expression in order to define the biochemical mechanism of IFN alpha signal transduction. IFN alpha stimulated genes (ISGs) are immediate response genes which utilize a pre-existing set of proteins to mediate their induction. A 15 bp IFN alpha-inducible enhancer element present in the promoters of IFN alpha stimulated genes, termed the IFN alpha stimulated response element (ISRE), is the genetic target for activation of ISGs. This DNA sequence is both necessary and sufficient for transcriptional activation and is the target for action of a positive transcription factor termed ISGF3. The active, DNA-binding form of ISGF3 is only found in cells which have been exposed to IFN alpha; however, it is activated from a silent form present in all responsive cells. ISGF3 is a multimeric complex assembled from cytoplasmic precursors which are translocated to the nucleus in response to IFN alpha. Assembly and translocation of ISGF3 is the earliest defined event in the IFN alpha response pathway. PMID- 1931719 TI - Maintenance therapy in the myeloproliferative disorders: the current options. AB - Recombinant interferon alfa-2a has been shown to be an effective induction agent in essential thrombocythaemia and thrombocythaemia associated with other myeloproliferative disorders, including chronic granulocytic leukaemia, polycythaemia rubra vera and myelofibrosis. Few data exist on the use of the recombinant interferons as maintenance agents in patients with thrombocythaemia. A cohort of 22 previously untreated patients, with essential thrombocythaemia, were treated with recombinant interferon alfa-2a maintenance therapy for a minimum period of 6 months. Effective long-term control of platelet counts, without evidence of haematological toxicity, was achieved in 19/22 patients. No objective haemorrhagic or thrombotic event occurred in 298 patient-months of interferon therapy. Three patients discontinued interferon alpha therapy due to adverse side-effects. Interferon alfa-2a is an effective maintenance agent in essential thrombocythaemia and is discussed in this context. PMID- 1931720 TI - Combination of cytokines: current status and future prospects. AB - Clinical trials with individual cytokines and extensive in vitro studies have provided the basis for the in vivo use of these molecules in combination. Animal models, with haemopoietic growth factors as well as preliminary studies in humans -as shown by our studies with the sequential use of IL-3 and GM-CSF in patients receiving intensive chemotherapy--indicate that the selection of the appropriate cytokines could optimize haematological responses according to particular clinical requirements. That immunotherapy with IL-2 can induce regression of disseminated human malignancies serves as an encouraging starting point for combinations with other cytokines with the goal of improving the therapeutic efficacy and reducing toxicity. Future prospects of combination therapy will be discussed. PMID- 1931721 TI - Analysis of lung asbestos content. PMID- 1931722 TI - Bronchial hyperreactivity in potroom workers and prognosis after stopping exposure. AB - A group of 30 potroom workers who developed an asthma-like syndrome during their work in the electrolytic extraction of aluminium (Alu-Swiss process with prebacked anodes) was followed up after stopping exposure. Subjective respiratory complaints were registered and a non-specific bronchial reactivity test using methacholine was performed once or twice during the follow up period (1984-9). After transfer to other work most workers either had an improvement in respiratory symptoms (60%) or even normalisation (27%); only 13% did not show changes. Bronchial hyperreactivity remained unchanged in 67% of workers, was less pronounced in 13%, normalised in 13%, and deteriorated in 7%. Smoking habits, atopy, and duration of exposure did not seem to have influenced the results obtained. No significant correlation was found between duration of exposure and the speed of onset of respiratory symptoms and the later prognosis of the syndrome. Based on the information collected during the period of observation it appears that reactive airway dysfunction syndrome, once induced, has a tendency to persist. An improvement in subjective complaints may be expected, however, after stopping exposure. PMID- 1931723 TI - Grain dust and respiratory health in South African milling workers. AB - Respiratory health was investigated in 224 grain milling workers. The likelihood of respiratory symptoms and chronic airflow limitation was raised for workers exposed to dust independent of the effects of smoking. Smokers were more likely than non-smokers to respond to a bronchodilator at the end of the working week. Dust was more strongly associated with most abnormal outcomes than was smoking. Subjective categories of exposure to dust were more strongly associated with most abnormal outcomes than were objective categories. The prevalence of all symptoms at the time of a survey conducted at the mill six years before was higher in workers who subsequently left the mill than in those who remained employed although the differences were not significant. PMID- 1931724 TI - Occupational aspects of epilepsy in the civil service. AB - Eighty five civil servants with epilepsy who were referred to the Civil Service Occupational Health Service over an 18 month period formed the study population. The reasons for these referrals and their outcomes have been analysed. The main reasons for referral were prolonged or frequent sickness absence, unsatisfactory work performance, epilepsy starting during employment, the discovery of undisclosed epilepsy, and for advice on working conditions. In 30 the outcome was medical retirement, although in only 15 was this due to epilepsy alone. Of the other 15, medical retirement was necessary in four because of the combination of epilepsy with another medical disorder, and in 11 because of a coincidental condition unrelated to their epilepsy. Only six out of 15 referred on account of epilepsy related sickness absence, and none of the 14 referrals due to epilepsy related unsatisfactory work performance resulted in early retirement. This reflected the invaluable role that the occupational physicians had in recognising where problems were due to poor control of the epilepsy or to the side effects of the antiepileptic medication and in arranging through general practitioners or hospital doctors for appropriate adjustment of the drug regimen. Nine of the 22 subjects who developed epilepsy during employment, however, were retired on medical grounds. PMID- 1931725 TI - Cancer of the testis, socioeconomic status, and occupation. AB - The risk of testicular cancer in relation to lifetime histories of socioeconomic status, occupation, and occupational exposures was examined in a case-control study in England. Interviews were conducted with 259 cases, 238 control patients treated at radiotherapy and oncology centres, and 251 controls who were hospital inpatients in other departments. Risk of testicular cancer was raised in men of high socioeconomic status measured both by occupation and in other ways, and was similar in relation to status measured at birth and at various later stages of life. The occupations with highest risk of the tumour were paper and printing workers, professionals, and administrators. Exposures to various specific occupational agents that have been suggested in publications as potential risk factors were examined, but none showed an association with risk. The relative risk for occupational exposure to ionising radiation was 1.62 (95% confidence interval 0.83-3.17). PMID- 1931726 TI - Risk of cancer for arc welders in the Federal Republic of Germany: results of a second follow up (1983-8). AB - An extended follow up of 1221 chromium and nickel exposed welders in the Federal Republic of Germany confirmed an increased relative risk of 1.6 for all cancers compared with an internal reference group of 1694 turners. In an external comparison an excess of deaths from malignant tumours compared with that expected from the national mortality rates was found (standardised mortality ratio (SMR) = 109), which was clearly related to both time since first exposure and duration of exposure. Mortality from lung cancer was increased among welders (SMR = 113) but also among turners (SMR = 108). The difference remained when the subgroups were compared according to smoking information. A large excess of mesothelioma as a cause of death could be attributed to exposure to asbestos. The significantly increased SMR seen for urogenital tumours and "other or unspecified tumours" showed, however, an inverse relation with time since first exposure. This and other inconsistencies in the analysis by type of welding do not permit conclusive statements. Thus a further extension of follow up seems warranted. PMID- 1931727 TI - Job strain and cardiovascular risk factors: a cross sectional study of employed Danish men and women. AB - As part of the World Health Organisation initiated MONICA project, 2000 men and women aged 30, 40, 50, and 60 from the general population were invited to undergo a medical examination with special emphasis on cardiovascular disease. A total of 1504 (75%) participated, 1209 of whom were employed. The participants answered a questionnaire on working, social, and health conditions and underwent clinical examinations that included the measurement of blood pressure and serum cholesterol, triglyceride, high density lipoprotein, fibrinogen, and glycated haemoglobin (HbA1C) concentrations. Using the demand-control model for measuring job strain suggested by Karasek, the employed people were classified according to those who had suffered job strain and those who had not in two different ways. The subjective classification was based on the participants' statements regarding demand and control in their jobs whereas the objective classification was based on job title and mode of payment. More women than men were classified as having high strain jobs. After adjusting for age and sex no significant association was found between coronary risk factors and subjective job strain. A tendency for an association between fibrinogen and job strain was found. Body mass index and HbA1C concentration were significantly associated with objective job strain independent of confounders. PMID- 1931728 TI - Obesity and hepatotoxins as risk factors for fatty liver disease. AB - Generally fatty liver disease (FLD) is attributed either to alcohol, diabetes mellitus, or obesity. To evaluate this commonly held clinical belief, a case control study of FLD in Western Pennsylvania was conducted with 19 cases being identified over a two year period. Cases of FLD were significantly heavier and were significantly more likely than controls to have exposures to either agents with recognised animal hepatotoxicity (odds ratio [OR] 8, p = 0.018) or to agents with potential hepatotoxicity--that is, documented in humans, animals, or expected on the basis of structure activity relations (OR = 4.5; p = 0.18). By contrast, they had not consumed significantly more alcohol than the controls. A logistic regression model of this experience suggests that both exposure to hepatotoxins and obesity are independent risk factors for FLD, which have an additive rather than a multiplicative interaction. Based upon these data, an occupational exposure to either recognised or potential hepatotoxins should be considered as a cause of liver dysfunction in subjects with FLD, independent of obesity and a history of alcohol consumption. PMID- 1931729 TI - Exposure to mixtures of solvents among paint workers and biochemical alterations of liver function. AB - The objective of this study was to determine biochemical alterations of liver function among paint manufacturers and sprayers associated with exposure to organic solvents. Two paint manufacturing factories and 22 various kinds of spray painting factories (16 car painting, two aircraft painting, three video terminal painting; and one trailer painting) were included. Air concentrations of organic solvents were collected by personal samplers and analysed by gas chromatography. A total of 180 workers were given a comprehensive physical examination, a questionnaire, a liver function test, and a test for hepatitis B surface antigen. The questionnaire contained questions regarding detailed personal medical history, intake of alcohol, and use of medicine. Mixtures of solvents were used throughout the factories, and xylene and toluene were the major components found in almost all air samples with average contents of 46% and 29% on a weight basis of 67 air samples. No strong hepatotoxic solvents were detected. Workers were classified according to the different exposure patterns and different air concentrations of breathing zones as: high (eight hour time weighted average (8 h TWA) hygienic effects of solvents 0.25-9.83, median 1.66), short term high (8 h TWA hygienic effects of solvents 0-3.38, median 0.12), and low (8 h TWA hygienic effects of solvents all below 0.38). After applying a multivariate model to control the non-occupational factors (alcohol, medication, age, and hepatitis B viral infection), increase in gamma-glutamyl transferase (GGT) activity was found to be associated with severity of exposure to the mixture of solvents. Because the possible effects on GGT activity of non-occupational factors were controlled for, it is concluded that increased GGT activity among exposed workers may be due to a higher exposure to the mixture of solvents. PMID- 1931730 TI - Relation between lead in surface tooth enamel, blood, and saliva from children residing in the vicinity of a non-ferrous metal plant in Belgium. AB - Two groups of schoolchildren between seven and 12 years old residing in the vicinity of a non-ferrous industrial plant and exposed to lead (Pb) at a concentration that could cause health problems, were monitored. Concentrations of Pb in blood (blood-Pb), which were determined at regular six monthly intervals, were related to the Pb concentrations in surface tooth enamel (enamel-Pb). Acid etch biopsy samples of surface enamel were taken at the end of the five year study period in the first group (A) and after two years in the second group (B). Salivary Pb (saliva-Pb) concentrations were determined for the first study group on the same day that the enamel biopsies were performed. Calibration of the data was necessary--that is, blood-Pb concentration with respect to age and sex and enamel-Pb concentration with respect to etch depth and age. The blood-Pb concentrations declined with time. Surface enamel Pb concentrations correlated with blood-Pb concentration for the period starting with the pre-eruptive development of the incisors, related to blood-Pb concentration for a long time, and corresponded partly to the exposure at the time of pre-eruptive development and/or eruption. Through the correlation with enamel-Pb concentration, the seasonal behaviour of blood-Pb concentration became apparent. Saliva-Pb concentrations related to blood-Pb concentrations only in the short term. PMID- 1931731 TI - Effects of exposure to cadmium on calcium metabolism: a population study. AB - The objective was to investigate the hypothesis that environmental exposure to cadmium may affect calcium metabolism in the population at large. The 1987 participants (965 men and 1022 women), from 20 to 80 years old, constituted a random sample of the population of four Belgian districts. The urinary excretion of cadmium, a measure of lifetime exposure, averaged 9.3 nmol/24 h in men (range 0.4-324 nmol/24 h) and 7.1 nmol/24 h (range 0.1-71 nmol/24 h) in women. Serum alkaline phosphatase activity and the urinary excretion of calcium correlated significantly and positively with urinary cadmium excretion in both men and women, and serum total calcium concentration negatively with urinary cadmium excretion in men only. The regression coefficients obtained after adjustment for significant covariates indicated that when urinary cadmium excretion increased twofold, serum alkaline phosphatase activity and urinary calcium excretion rose by 3-4% and 0.25 mmol/24 h respectively, whereas in men serum total calcium concentration fell by 6 mumol/l. After adjustment for significant covariates the relation between serum total calcium concentration and urinary cadmium excretion was not significant in women. The findings suggest that even at environmental exposure levels calcium metabolism is gradually affected, as cadmium accumulates in the body. The morbidity associated with this phenomenon in industrialised countries remains presently unknown and requires further investigation. PMID- 1931732 TI - Dust exposure in coeliac disease: a case-referent study. AB - Case series of coeliac disease show that chronic allergic alveolitis (farmers' lung) and fever reactions due to exposure to organic dust (organic dust toxic syndrome) commonly occur among subjects with coeliac disease and dermatitis herpetiformis, these being related disorders. In this case-referent study 105 cases of coeliac disease and dermatitis herpetiformis were compared with 237 referents from the general population by means of a mail inquiry regarding exposure to various environmental factors. Increased odds ratios were obtained with exposure to various farm animals and more clearly for cotton dust, although numbers were few. Animal husbandry in Sweden invariably means heavy exposure to organic dust. The fact that comparatively few persons reported dust exposure may be of doubtful validity in view of the high frequency of exposure to farm animals reported by the cases. PMID- 1931733 TI - A "scorpion fish" (Trachinus vipera) sting: fishermen's hazard. AB - "Scorpion fish" is a nickname given by fishermen to members of the Trachinidae family as a result of their unusual stinging mechanism. These fish are found throughout the eastern Atlantic region from the North Sea through the Mediterranean and Black Seas and along the western coast of Northern and Central Africa. They are characterised by poisonous glands located at the base and sides of the spines of their anterior back fin and at the base of a spine located on the gill cover. Because of the unusual location of the glands, fishermen handling these fish frequently suffer local injuries. A case of necrosis of the tip of the middle finger after a "scorpion fish" sting is described. PMID- 1931734 TI - The distribution of the HLA-DQ alpha alleles and genotypes in the Finnish population as determined by the use of DNA amplification and allele specific oligonucleotides. AB - Allele and genotype frequencies for the HLA-DQ alpha locus were determined for use in forensic analyses and paternity tests in Finland. The polymerase chain reaction (PCR) and the reverse dot blot format were employed to detect 6 different HLA-DQ alpha alleles. All 6 HLA-DQ alpha alleles were detected among the 112 unrelated individuals with allele frequencies ranging from 5.8% to 32.6%. The distribution of the observed genotypes is in Hardy-Weinberg equilibrium. Additionally, this Finnish population sample is statistically similar to 2 other Caucasian sample populations. The power of discrimination of this system in the Finnish population sample is 0.92, suggesting this method may prove suitable for identification purposes. PMID- 1931735 TI - A comparative study of diazepam levels in bone marrow versus serum, saliva and brain tissue. AB - The distribution of diazepam in biological fluids and tissues of rats was examined 1, 2, 4 and 8 h after intraperitoneal administration by using a radioimmunoassay with specific anti-diazepam antibody. The diazepam levels in serum, saliva, brain and bone marrow decreased over a period of 2 h and levelled off 4 h after administration. The diazepam concentration in bone marrow was much higher than in serum, saliva and brain, suggesting an accumulation of diazepam in this tissue. This indicates that bone marrow could be a very useful material for the detection of diazepam in skeletonized remains. The diazepam concentrations in bone marrow, serum, saliva and brain showed a linear relationship (r = 0.860 0.997), indicating that a valid estimate of diazepam concentration in blood can be made from bone marrow samples. PMID- 1931736 TI - Sexing of forensic samples using PCR. AB - A rapid protocol has been established for sexing forensic samples by the Polymerase Chain Reaction method. Three sets of primer were used, two specific for Y chromosome repetitive sequences and one specific for X chromosome repetitive sequences. Detailed procedures of experiments, the controls and the applications to testing bloodstains and a vaginal swab are presented. The sensitivity of the test and problems due to contamination are discussed. PMID- 1931737 TI - Cerebral lesions and causes of death in male alcoholics. A forensic autopsy study. AB - Autopsies on 195 male alcoholics aged 30-64 years who died outside hospitals and nursing homes in Oslo from 1984 to 1988, were carried out at the Institute of Forensic Medicine, Rikshospitalet. In 127 cases brain tissue was examined neuropathologically, 86 (67.7%) showed abnormalities and 28 contained lesions of more than one type. Lesions associated with alcoholism were found in 61 cases (48%), 18 (14.2%) showed Wernicke's encephalopathy, 47 (37%) cerebellar atrophy, 2 central pontine myelinolysis and 1 hepatic encephalopathy. Subdural haematoma and/or cortical contusions were found in 30 cases (23.6%) and cerebrovascular lesions in 19 (15%). Of the 195 cases, 22 had a history of recurrent convulsive attacks of which 19 were examined neuropathologically and 13 had focal damage that could have caused epileptic fits. Although cerebral damage was more frequent among vagrants and other persons dependent on social support, 50% of the alcoholics living in their own homes were also affected. Alcohol-related disease was considered the cause of death in 15 of 127 cases examined neuropathologically and 9 of these died from acute Wernicke's encephalopathy all of whom were sober at death. Although the post mortem analyses included neuropathological examination of the brain, the cause of death remained unknown in 27 (21%) of the 127 cases. PMID- 1931738 TI - Immunohistochemical investigations to demonstrate vital direct traumatic damage of skeletal muscle. AB - The muscle proteins actin, myosin, desmin and myoglobin were investigated in traumatically damaged human and animal skeletal muscle using an immunohistochemical PAP-method. A depletion of all the proteins investigated was observed in muscle fibres damaged in the antemortem period. The antigens could however also be demonstrated in the otherwise empty sarcolemma, the discoid disintegration zones of the fibres and between the fibres. The depletion begins immediately after the trauma and myoglobin is the first to be affected. No such changes could be observed after post mortem muscle damage. The antigens could be demonstrated until 72 hours post mortem. The demonstration of protein depletion is an important addition to the light microscopical findings in vital muscle alterations. PMID- 1931739 TI - Population genetics of four hypervariable loci. AB - Populations of white Caucasians, Afro-Caribbeans and Asians residing within the UK have been analysed at 4 different hypervariable loci. A computerised system was used to store and to analyse the data. Simulation experiments were carried out in order to determine whether there was any evidence for population stratification, which would lead to non-independence of allelic distributions. PMID- 1931740 TI - PCR-based typing of DNA extracted from cigarette butts. AB - Limited genetic marker information can be obtained from saliva by typing by conventional serological means. Thus, the application of PCR-based DNA typing methods was investigated as a potential approach for typing genetic markers in saliva. DNA was isolated from 200 cigarettes smoked by 10 different individuals (20 cigarettes per individual) and from 3 cigarette butts recovered from 2 crime scenes (adjudicated cases) using a Chelex 100 extraction procedure. The amount of recovered human DNA was quantified by slot-blot analysis and ranged from approximately less than 2-160 ng DNA per cigarette butt for the 200 samples, and 8 ng, 50 ng, and 100 ng for the cigarette butts from the adjudicated cases. The DNA was successfully amplified by the polymerase chain reaction (PCR) for the HLA DQ alpha locus (99 out of 100 samples) as well as for the variable number of tandem repeat (VNTR) locus D1S80 (99 out of 100 samples). Amplification and typing of DNA was successful on all samples recovered from the crime scenes. The results suggest that PCR-based typing of DNA offers a potential method for genetically characterizing traces of saliva on cigarette butts. PMID- 1931741 TI - Intensive gunshot residues at the exit wound: an examination using a head model. AB - The autopsy findings of intensive gunshot residues at the exit wound after a gunshot wound in the head led to an experimental investigation to clarify the mode of origin and intensity of these gunshot residues on the inner surface of the exit wound. For this purpose a simple skull/brain model was prepared. The results of the examination showed that with weapons of the same calibre distinct gunshot residues should be expected at the exit wound. PMID- 1931742 TI - A case of high opiate tolerance: implications for drug analyses and interpretations. AB - A case of driving under the influence of extremely high concentrations of codeine and ethylmorphine is reported. A high blood concentration of morphine was also found, which in this case was probably a metabolic product of codeine and ethylmorphine. This illustrates that when morphine is found in blood, the sample should also be analysed for other opiates in order to avoid misinterpretations. PMID- 1931743 TI - Fatal air embolism during female autoerotic practice. PMID- 1931744 TI - Self reported compliance and the effectiveness of prenatal dental education. PMID- 1931745 TI - The needleless syringe: efficacy of anesthesia and patient preference in child dental patients. AB - Delivery of local anesthesia in dentistry is primarily by way of a needle-tipped syringe. This procedure, when used on children, is often stressful and sometimes painful for the patient. The Syrijet is an instrument which delivers anesthesia without the use of a needle. This is accomplished by delivering the anesthetic solution under high compressive forces. The subjects were thirty-four children ranging in age between 5 and 15 years, on whom forty-five dental procedures were completed. There was a statistically significant difference in favor of the instrument, with twenty-five subjects reporting a preference for it. The instrument was completely successful in providing anesthesia in thirty-six of the forty-five procedures. PMID- 1931746 TI - Surface-specific effect of a mineralizing agent on the permanent teeth and on periodontal status. AB - In a two-year clinical trial the surface-specific effect of a mineralizing agent on selected permanent teeth was evaluated as well as the effect of this agent on periodontal health in children. Compared with positive controls (Control group, n = 123, biweekly mouthrinsing with placebo and 0.2% NaF solutions), among children in the test group (n = 123, biweekly mouthrinsing with 2% Remodent and 0.2% NaF solutions) the mineralizing agent clearly affected periodontal health (as determined by the prevalence of subjects with gingival bleeding and occurrence of affected sextants at risk) positively, in addition to having a positive effect on the incidence of EFD lesions. The mineralizing agent tested was not found to have adverse effects (as determined by the prevalence of subjects with dental calculus and occurrence of affected sextants at risk). Use of the mineralizing agent is recommended especially during posteruptive maturation of permanent teeth. PMID- 1931747 TI - Double teeth: case reports. PMID- 1931748 TI - The nonsteroidal anti-inflammatory drugs in the treatment of periodontal disease. PMID- 1931749 TI - Are Medicaid fraud control units the real fraud? 2. PMID- 1931750 TI - Orthodontic-orthopedics as related to respiration and conductive hearing loss. PMID- 1931751 TI - The effects of the MYO appliance in children with malocclusions of the primary dentition. PMID- 1931752 TI - Dual block appliance in treatment of a developing Class III malocclusion in a 7 year-old boy. PMID- 1931753 TI - Tumour ploidy, morphometry, histological grading and clinical features in ovarian carcinoma: mutual relations. AB - The relationship between tumour ploidy and qualitative and quantitative histopathology was assessed in a series of 95 ovarian carcinomas. 67% of the tumours were non-diploid (DNA aneuploid). 56% of the early stage (I-II) tumours were non-diploid and 81% of the tumours in advanced (III-IV) stages were aneuploid. Histological grading failed to show a clear relationship between increasing malignancy grade and ploidy. There was a close association between DNA ploidy and nuclear perimeter, area and shortest and longest nuclear diameter: the nuclei of non-diploid tumours were generally larger. Also the number of mitotic figures per square millimeter of epithelium in the microscope image (volume corrected mitotic index, M/V-index) differed significantly between near-diploid and non-diploid tumours. Discriminant analysis showed that 74% of the learning set tumours (67% of the test set tumours) could be correctly classified in low ploidy and high-ploidy categories with morphometric features (nuclear perimeter, M/V-index and volume percentage of epithelium). Characteristic features of non diploid ovarian tumours--rapid proliferation and large nuclear size--could be assessed with morphometric methods which allowed a relatively large aneuploid tumour group to be distinguished. PMID- 1931754 TI - Flow cytometric and histomorphometric analysis of limitations of clinical breast cytomorphometry. AB - The clinical value and limitations of a previously described cytomorphometric method, based on nuclear size and anisonucleosis, for evaluation of routine fine needle aspiration of the breast were assessed in a series of 313 histologically investigated primary breast lesions. Limitations were analyzed by histomorphometry and DNA flow cytometry in 116 consecutive cases of histologically confirmed breast carcinoma. Eighty per cent of histologically proven malignant tumours were classified cytomorphometrically as malignant and no false-positive results were encountered. For benign lesions a benign cytomorphometric classification was reached in 66% of the cases. Histomorphometry showed that on the whole the assignment of histologically malignant tumours to a non-malignant cytomorphometric classification was determined by smaller nuclei and not by sampling error. Tumours assigned to a malignant cytomorphometric classification had on average significantly higher DNA indices than did tumours not assigned to a malignant cytomorphometric classification (P less than 0.001). The mean-nuclear areas in cytomorphometry and histomorphometry were strongly correlated with DNA indices indicated by DNA flow cytometry (P less than 0.001 for both). The present findings show that this cytomorphometric method is appropriate for routine quality control of a cytological diagnosis of malignancy in FNA of the breast. However, an inconclusive result in 15-25% of the tumours is inevitable. PMID- 1931755 TI - Selected bibliography. PMID- 1931756 TI - Combined effects of different class I antiarrhythmic agents on maximum rate of depolarization (Vmax) of action potentials in guinea-pig papillary muscles. AB - The combination of two different kinds of class I antiarrhythmic agents (class Ia, Ib, or Ic) was examined with regard to their effects on the maximum rate of depolarization (Vmax) of action potentials in guinea-pig papillary muscles. The combinations of disopyramide plus lidocaine, disopyramide plus mexiletine, mexiletine plus flecainide, and disopyramide plus flecainide were employed to study their effects on use-dependent block of Vmax. All the combinations increased the percent of use-dependent block at most of the frequencies employed (0.1-3.3 Hz) as compared to the effects of the single use of either drug, but no decrease in use-dependent block was found with any of the combinations. The time courses of the development of use-dependent block by disopyramide, lidocaine, and mexiletine were best expressed by two exponential functions, whereas those by flecainide were expressed by a single exponential function. Disopyramide plus lidocaine and disopyramide plus mexiletine produced increases in the time constant of the fast component of the block (tau f), the fast fraction of the block (Af), and the ratio of the fast to the slow fraction (Af/As). Mexiletine plus flecainide increased tau f, Af, and As; whereas disopyramide plus flecainide caused no changes in the kinetic parameters of use-dependent block. These results suggest that there may be diverse modes of interaction between the drug and the Na+ channel, and the combination of two different types of the drug may sometimes provide different effects on the fast and slow components of the use-dependent block of Vmax. PMID- 1931757 TI - Effects of combined use of class I antiarrhythmic agents on Vmax of guinea-pig ventricular muscles. AB - The effects of the combined use of class-I antiarrhythmic drugs on the resting potentials (RP), amplitude of action potential (AMP), and Vmax of the action potential were investigated in guinea-pig ventricular papillary muscles that were superfused with oxygenated Krebs-Ringer solution at 35 degrees C. Disopyramide (40 microM) reduced Vmax to 68.6 +/- 3.1% (mean +/- SE, n = 5) of the control with minimal changes in RP and AMP when preparations were stimulated at 1 Hz. The addition of mexiletine (20 microM) to the solution containing disopyramide (40 microM) caused a minimal reduction of Vmax (less than 5%) for the stimulation of 1 Hz, but a significant reduction of Vmax (13% p less than 0.05) when stimulation was increased to 2 Hz. This amount of the reduction is compatible with that obtained by mexiletine alone, suggesting a simple additive Na+ channel inhibition by this drug combination. This additive effect was also observed in the recovery process of Vmax from the use-dependent block induced by train stimuli at 1 Hz. Flecainide (5 microM) reduced Vmax to 58.6 +/- 13.3% (n = 5). The addition of mexiletine to the superfusate with flecainide produced a further depression of 14 +/- 2.6% of Vmax, even at 1 Hz. This depression was larger than that produced by mexiletine, suggesting a synergistic action of the two drugs on the Na+ channel. Such information about the interaction of the class I drug combinations with the Na+ channel may be clinically important. PMID- 1931758 TI - Combination therapy with aprindine and verapamil for paroxysmal supraventricular tachycardia as assessed by transesophageal atrial pacing. AB - To assess the efficacy of combination therapy of aprindine (40 mg/day) and verapamil (160 mg/day), transesophageal programmed atrial stimulation was performed on 21 patients with paroxysmal supraventricular tachycardia (including 12 patients with atrioventricular nodal reentrant tachycardia and nine patients with atrioventricular reentrant tachycardia) under four conditions: a) control, b) aprindine alone, c) verapamil alone, and d) aprindine + verapamil. RESULTS: a) Aprindine, verapamil, and aprindine + verapamil prevented paroxysmal supraventricular tachycardia induction in 2/21, 3/21, and 9/21 patients, respectively; b) aprindine + verapamil prolonged the cycle length of paroxysmal supraventricular tachycardia more than aprindine or verapamil alone; c) aprindine, verapamil, and aprindine + verapamil decreased the AV blocking rate by 15, 23, and 35 beats/min, respectively, in comparison with the control state; d) aprindine, verapamil, and aprindine + verapamil prolonged the effective refractory period of atrioventricular conduction system by 20, 34, and 76 msec, respectively, compared with the control state. In conclusion, aprindine + verapamil appear to be more effective than aprindine or verapamil alone in preventing paroxysmal supraventricular tachycardia with nodal reentry, but there was less benefit in those without nodal reentry (Wolff-Parkinson-White group). PMID- 1931759 TI - Combination antiarrhythmic treatment among class Ia, Ib, and II agents for ventricular arrhythmias. AB - Ventricular arrhythmia suppression trials were performed to compare the efficacies and side effects of disopyramide and mexiletine used alone and in combination, and to compare the efficacies and side effects of mexiletine and propranolol used alone and in combination, in patients with chronic ventricular premature contractions (VPCs, greater than or equal to 3000 beats/day). The study on the combination of disopyramide and mexiletine included 26 patients (19 men and 7 women). Disopyramide 100 mg tid or mexiletine 150 mg tid was administered as single-drug therapy, and disopyramide 50 mg plus mexiletine 100 mg tid was administered as combination therapy. Each patient underwent Holter monitoring during four different periods: baseline, disopyramide alone, mexiletine alone, and combination therapy. The mean number of VPCs/hr at baseline was 796 +/- 522 (mean +/- SD), which was significantly decreased with all three therapies (p less than 0.01 in each) to a) 415 +/- 480 with disopyramide alone, b) 341 +/- 368 with mexiletine alone, and c) 345 +/- 408 with the combination therapy. The number of patients demonstrating a significant reduction in VPCs (greater than or equal to 75%) and the elimination of ventricular tachycardia (VT; three or more consecutive VPCs) did not differ significantly among the three therapies. The prematurity index (PI), vulnerability index (VI), and QTc tended to be aggravated by disopyramide therapy alone, but these values were corrected by combination therapy. No patients withdrew from the study due to side effects during combination therapy, although three patients withdrew from the study due to severe side effects during single-drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931760 TI - Hodgkin's disease of the liver; prognosis and possible indications for radiotherapy. AB - A retrospective analysis of 56 patients presenting with Hodgkin's disease involving the liver between 1970 and 1984 revealed a 10-year survival probability of 44%. The actuarial 10-year continuous progression free survival was 42%. Presentation variables predicting for relapse in the liver included hepatomegaly (P less than 0.025) or focal lesions on isotope, ultrasound or CT scan (P less than 0.01). These factors may define a context for investigation of adjuvant hepatic irradiation following chemotherapy. PMID- 1931761 TI - Radiotherapy after conservative surgery for breast cancer: selective use of iridium-192 wire boost to tumour bed in high risk patients. AB - The results of treatment for 51 patients referred for radiotherapy after local excision of an 'early' breast carcinoma are reviewed. The patients were considered to be at particularly high risk of local recurrence due to the presence of one or more adverse histological features, most commonly microscopic involvement of resection margins. The patients received a course of whole-breast irradiation (40 Gy in 15 fractions over 3 weeks) but instead of following this with a routine photon or electron tumour-bed boost (15 Gy in five fractions) these patients received an iridium-192 wire implant, giving a tumour-bed boost of 25 Gy over approximately 3 days. After a median follow-up of 38 months, five patients have recurred locally within the breast, giving an actuarial breast recurrence-free survival of 87.8% at 8 years. Four patients have died of metastatic breast cancer, none of whom had uncontrolled local disease. Cosmesis was good or excellent in 76% of cases. The presence of microscopic tumour at resection margins or other adverse histological features is not, therefore, necessarily an indication for further surgery, as a good level of local control can still be achieved with radiotherapy providing a relatively high-dose tumour bed boost is employed using an iridium-192 wire implant. PMID- 1931762 TI - Weekly etoposide, methotrexate and actinomycin D, alternating with cyclophosphamide plus vincristine (EMA/CO): a phase II study in advanced gastric carcinoma. AB - A total of 27 patients with measurable/evaluable metastatic or locally advanced gastric carcinoma were given combination chemotherapy comprising etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA/CO). Ten achieved partial remission, giving a response rate of 37% (95% CI; 21.7%-66.3%), 12 attained stable disease, whereas five had disease progression despite treatment. Drug toxicity was moderate to severe. Five of those who achieved partial remission underwent an attempt to resect residual disease which was successful in only three patients. PMID- 1931763 TI - The evolution of spinal growth after irradiation. AB - Spinal growth has been monitored in 13 children treated with craniospinal irradiation for brain tumours. Six were irradiated prepubertally and seven peripubertally, all with 30 Gy to the whole spine over four weeks. The change in (subischial leg length (SILL)--sitting height (SH)) standard deviation score (SDS) was used as an index of disproportionate segmental growth, which allowed the influence of growth hormone deficiency on growth to be discounted. Spinal growth over the prepubertal years was relatively normal: annual change in (SILL SH) SDS was +0.07 SD 0.2. However, over puberty, annual change in (SILL-SH) SDS had increased significantly to +0.41 SD 0.14 (P = 0.03). If irradiated peripubertally, annual change in (SILL-SH) SDS to final height was +0.22 SD 0.23, not significantly different from the change over puberty in the prepubertal group. Relatively normal spinal growth after irradiation in the prepubertal child should be interpreted with caution, as it is during puberty that skeletal disproportion manifests itself. PMID- 1931764 TI - The Skinner Lecture: a cost-benefit analysis of postoperative radiotherapy in the treatment of early breast cancer. PMID- 1931765 TI - A computerized system for radiotherapy logging. PMID- 1931766 TI - Primary Hodgkin's disease of bone. AB - Primary Hodgkin's disease of bone is rare. Diagnosis is often delayed and may be mistaken for eosinophilic granuloma. We report such a case where Hodgkin's disease presented as a primary osteolytic bone lesion. PMID- 1931767 TI - Intravaginal iridium-192 in the management of embryonal rhabdomyosarcoma. AB - Three patients with vaginal rhabdomyosarcoma and residual vaginal disease following surgery and chemotherapy have been treated using high dose irradiation with vaginal moulds loaded with iridium-192. These patients remain well and disease-free seven years, 30 months and 18 months after their initial presentations. This paper describes a technique for local vaginal irradiation with individualized vaginal moulds made using a rapid-setting silastic foam impression and loaded with a single plane of iridium wires. Details of the dosimetry are also included. PMID- 1931768 TI - Fournier's gangrene: a hazard of chemotherapy in AIDS. PMID- 1931769 TI - Breast conservation, the problem of treating the excision site effectively: physical criteria for the choice of technique used. AB - This paper examines how physical factors such as the depth of the excision cavity below the skin surface and its distance from the underlying lung may impact upon the choice between the use of an electron field (from a Varian Clinac 1800) or an implant (using a double plane of iridium-192 wires). Data have been derived from a phantom dosimetry experiment simulating different permutations of breast size and depth of excision cavity. An anthropomorphic female phantom with two different-sized wax breast phantoms has been used to simulate the clinical circumstances envisaged and isodose distributions have been estimated from an array of TLD readings. The biological significance of doses measured in skin and lung have been examined using the linear-quadratic (LQ) model. Both on physical and biological grounds, the results favour the implant under the experimental conditions adopted. The use of the electron beam to definitively treat the excision cavity (omitting breast tangents) to 60 Gy would result in unacceptable late effects in the skin and an observable incidence of pneumonitis if the excision cavity were near the chest wall. Small carcinogenic risks, particularly to the lung, are apparent with each modality, but may be moderated for the iridium-192 implant by a reduced carcinogenic potential associated with low-dose rate radiation. The use of the newer radionuclides iodine-125 and samarium-145, with less penetrating gamma ray emissions, might be preferred to iridium-192 from the point of view of bronchial carcinogenesis if definitive treatment of the excision cavity became widespread practice. PMID- 1931770 TI - Boost dosage to the excision site following conservative surgery for breast cancer: it's easy to miss! AB - Surgical haemoclips have been left in situ in 27 consecutive patients conservatively operated on for early breast cancer by two surgeons in Newcastle, New South Wales, to demarcate the limits of the excision cavity for accurate postoperative irradiation. As anticipated, the position of these clips varied widely in relation to the patient's recollection of the position of the original lump, the surgical notes, and the surgical scar. In addition the dimensions of the clipped area also varied considerably. So great was the variation in position of the clips that incomplete coverage of the excision cavity in the 'coronal' (en face) plane using an electron field could have occurred in an estimated 10/24 (42%) evaluable cases had surgical clips not been left in situ. Depth of the surgical clips below the skin surface also varied markedly between patients. In 19/26 (73%) evaluable cases the clips were observed to be sited 3 cm or more below the skin surface, while in only 5/26 (19.2%) were the clips found to be 2 cm or less deep to the surface. Had a 9 MeV beam from our Clinac 1800 been used to treat all the cases, a major underdose of the excision cavity would have been likely in 21/26 (81%) evaluable cases. This figure would be improved to 11/26 (42%) had a 12 MeV beam been used--still a very high figure. Neither of these points have received much attention in the literature. This small study sounds a distinct warning and needs to be repeated on a larger scale. PMID- 1931771 TI - Prostate irradiation does not affect the serum prostatic acid phosphatase level. AB - Twenty-nine consecutive patients with localized prostatic carcinoma were studied prospectively to assess the effect of radical pelvic irradiation on the serum prostatic acid phosphatase level (SPAPL). The doses of radiation given ranged from 64.00 to 66.00 Gy. SPAPLs were taken before, during and shortly after their treatment. No significant individual variations in SPAPLs were found. When patients with prostatic carcinoma show rises in serum prostatic acid phosphatase during or after pelvic irradiation, these are unlikely to be due to their treatment and occult pelvic nodal or bony disease should be considered. PMID- 1931772 TI - Primary lymphoma of bone: a review of 13 cases emphasizing orthopaedic problems. AB - The records of 13 patients treated in the radiotherapy department in Newcastle 1973-1988 for primary lymphoma of bone (PLB) were reviewed. Treatment was by radiotherapy in combination with surgery and/or chemotherapy. Cause-specific disease-free survival at 5 years in 75%. Eight patients had PLB in a weight bearing bone: four of these patients suffered pathological fractures in the treated bone. The radiological differentiation of recurrent PLB and radiation osteitis remains unsatisfactory. None of the four post-treatment pathological fractures in this series was due to recurrent PLB. None of these fractures healed spontaneously. All four patients remain disease-free but all have restricted mobility and require walking aids. PLB in weight-bearing bones is associated with long-term fragility and propylactic stabilization of the affected bone should be considered. PMID- 1931773 TI - Alpha-interferons: impact on survival of patients with renal cell carcinoma. AB - We studied the effect of treatment on tumour response and survival of 76 evaluable patients with renal cell carcinoma, treated in this unit over a 12-year period. For the purpose of this study patients were classified into three groups according to the treatment they received: (a) 22-patients were evaluable for treatment with alpha-interferons; (b) 20 for treatment with immune modulation, other than interferon; (c) 34 patients received hormone treatment, chemotherapy or had no systemic treatment. Objective tumour regressions were observed only among patients who received interferon. No difference in overall survival from first diagnosis or from diagnosis of Stage IV disease could be demonstrated in these three groups. Alpha-Interferons are the first agents to induce clinically meaningful and reproducible regression of metastases in renal cell carcinoma. This treatment, however, has not been shown to have a major impact on survival. PMID- 1931774 TI - Fertility following cancer therapy. AB - This article reviews the literature relating to fertility following cancer therapy. Normal fertility clearly relies on normal gonadal and normal sexual function. Consideration is given here to the possible effects of surgery, radiotherapy and chemotherapy on fertility. Surgical techniques have now been described which in selected patients may allow normal erectile and ejaculatory function in the male, where previously impotence was inevitable. Maintaining radiation doses to the testes and ovaries to a minimum will reduce the incidence of radiation-induced sterility and may allow recovery of gonadal function. It is clear that cytotoxic chemotherapy does not inevitably result in permanent sterility. Some regimens are more toxic in this respect than others, and reducing the number of courses may improve the chances of retaining fertility. Hormonal manipulations designed to protect the gonad against cytotoxic damage have thus far been unsuccessful in the clinical situation. PMID- 1931775 TI - Acute non-lymphocytic leukaemia and myelofibrosis following sequential hemibody irradiation for prostatic carcinoma. AB - Sequential hemibody radiotherapy (SHBI) is currently being evaluated in clinical trials as adjuvant treatment in cancer patients who are potential long-term survivors. The potential late adverse effects of this therapeutic modality on the bone marrow may place patients at risk for the complications of aplasia, leukaemia, and myeloproliferative syndromes. We describe a case of acute non lymphocytic leukaemia and myelofibrosis following SHBI for prostate carcinoma. The possible role of radiation in the induction of these abnormalities is discussed. PMID- 1931776 TI - Blindness in patients after external beam irradiation for pituitary adenomas: two cases occurring after small daily fractional doses. AB - We report two cases of blindness occurring within 10 months of completion of radiation with 45 Gy in 1.80 Gy fractions given five times weekly. The literature on blindness as a complication of pituitary irradiation is reviewed. There have been no reported cases of total visual loss occurring as a consequence of treatment with fractional doses of less than 2 Gy. Visual loss due to radiation damage usually occurs within two years of completion of treatment in contrast to visual loss due to recurrence or empty sella syndrome, which usually occur more than two years after the completion of therapy. Other causes of blindness not related to the radiation, and potentially reversible, must be considered. However, these causes usually have a distinctively different clinical picture. Fraction size, total dose, and treatment time are all important factors when considering the biological effects of radiation to the pituitary region. PMID- 1931777 TI - Axillary dissection in early breast cancer. PMID- 1931778 TI - The Lederle Trainee Oncologist Award Essay 1990--how I would manage cancer patients in the year 2000. PMID- 1931779 TI - Reoperation after cholecystectomy. The role of the cystic duct stump. AB - The so-called "Postcholecystectomy Syndrome" may be due to various pathological biliary causes. The aim of this study was to evaluate the significance of the cystic duct stump syndrome and if so, how often a long (greater than 1.5 cm) cystic duct stump was an indication for reoperation on the bile ducts after cholecystectomy in our patients. Three hundred and twenty two patients underwent a second operation on the bile ducts after cholecystectomy in the last ten years. In 35 patients (10.8%) a striking findings was a long cystic duct stump (greater than 1.5 cm). In 24 of these patients, a pathological finding, in addition to the long cystic duct stump, was found on exploration. Out of these 24 patients there were 14 with common bile duct stones; 6 with stenosis of the sphincter of Oddi; 3 with chronic pancreatitis and in one patient hepatitis was the cause of the symptoms. From the remaining 11 patients 8 had a stone in a partial gall bladder or cystic duct stump. One patient had a fistula between the cystic duct stump and duodenum and one a suture granuloma. There was only one patient where a 1.5 cm long cystic duct stump remnant was the only pathological finding. Four years after reoperation this patient is still suffering from the same intermittent gastrointestinal symptoms. We conclude that the cystic duct stump is hardly ever a cause for recurrent symptoms in itself. Total excision of the cystic duct does not eliminate the existence of postcholecystectomy symptoms. PMID- 1931780 TI - Hepatic surgery facilitated by a new jet dissector. AB - Increasing experience with major hepatic resections has stimulated the development of improved resectional techniques and tools. A new high velocity water jet dissector is reported which offers significant advances over previously developed ultrasonic and low pressure water jet machines. It has been successfully used in 8 major hepatic resections with minimal blood loss, excellent visibility and without complications. The dissector is also of value in the exposure of intrahepatic bile ducts for biliary-enteric anastomosis. PMID- 1931781 TI - The value of routine biochemical tests in discriminating between malignant and benign pancreatic tumours. AB - The probability that routine hematological laboratory tests of liver and pancreatic function can discriminate between malignant and benign pancreatic tumours, incidentally detected during operation, was investigated. The records of 53 patients with a verified diagnosis of pancreatic carcinoma and 19 patients with chronic pancreatitis were reviewed with regard to preoperative total bilirubin, direct reacting bilirubin, alkaline phosphatase, glutamyltranspeptidase, aminotransferases, lactic dehydrogenase and amylase. Multivariate and discriminant analysis were performed to calculate the predictive value for cancer, using SYSTAT statistical package in a Macintosh II computer. Total and direct reacting bilirubin and glutamyltranspeptidase were significantly higher in patients with pancreatic carcinoma. However, only considerably increased levels of direct reating bilirubin were predictive of pancreatic carcinoma. PMID- 1931782 TI - Primary leiomyosarcoma of the liver. AB - A case of primary leiomyosarcoma of the liver is described and the problems in diagnosis and management are discussed together with a review of the available literature. These tumours have a favourable prognosis when diagnosed preoperatively and the value of electron microscopic findings in this situation are highlighted. PMID- 1931783 TI - Endotoxaemia in obstructive jaundice. PMID- 1931784 TI - Etiology and pathogenesis of marked elevation of serum transaminase in patients with acute gallstone disease. AB - From 1980 through 1988, biliary surgery was performed in 197 patients with acute gallstone disease and concomitant elevation of serum glutamic oxalacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) of over 300 Karmen units. In 137 patients, anatomic inspection and liver biopsy were performed during the acute stage of the disease. Impacted and floating bile duct stones were found in 69 (50%) and in 43 (32%) of the 137 patients, respectively. The main liver histology was necrosis of liver cells. After surgery, high serum transaminase fell rapidly with immediate recovery in 99% of the patients. In the remaining 60 patients, their signs and symptoms settled soon after initial conservative treatment and surgery was performed after an average time of 21 days. At laparotomy, impacted bile duct stones were found in 2 (3%) and liver histology revealed regeneration of liver cells. These findings suggest that marked elevation of serum transaminase in patients with acute gallstone disease might be due to an acute inflammatory liver cell injury caused by impacted bile duct stones or migrating stones, which would be transient and reversible after early resolution of the bile duct obstruction. PMID- 1931785 TI - Measurement of liver blood flow: a review. AB - The study of hepatic haemodynamics is of importance in understanding both hepatic physiology and disease processes as well as assessing the effects of portosystemic shunting and liver transplantation. The liver has the most complicated circulation of any organ and many physiological and pathological processes can affect it. This review surveys the methods available for assessing liver blood flow, examines the different parameters being measured and outlines problems of applicability and interpretation for each technique. The classification of these techniques is to some extent arbitrary and several so called "different" methods may share certain common principles. The methods reviewed have been classified into two groups (Table 1): those primarily reflecting flow through discrete vessels or to the whole organ and those used to assess local microcirculatory blood flow. All techniques have their advantages and disadvantages and in some situations a combination may provide the most information. In addition, because of the many factors affecting liver blood flow and sinusoidal perfusion, readings in a single subject may vary depending on positioning, recent food intake, anxiety, anaesthesia and drug therapy. This must be borne in mind if different studies are to be meaningfully compared. PMID- 1931786 TI - Iatrogenic chymobilia--a disease of the nineties? PMID- 1931787 TI - Hepatic surgery in the USSR. PMID- 1931788 TI - Liver atrophy associated with monolobar Caroli's disease. AB - The association of the atrophy-hypertrophy complex in monolobar Caroli's disease (Type I) is reported in a 30 year old male who presented with recurrent cholangitis. Ultrasound and CT scan showed localised, right sided, saccular biliary dilatation in a normal sized liver. Severe right lobar atrophy was detected at operation and the resected right lobe weighed only 140 gms. Distortion of the hilar vascular anatomy and posterior displacement of the right hepatic duct orifice were problems encountered at surgery. PMID- 1931789 TI - Primary "brown pigment" bile duct stones. AB - Bile duct stones from 42 patients were morphologically and chemically analysed. The calculi from 27 patients had important primary bile duct stone (PBDS) features, consisting of a general ovoid shape and fragile structure, with alternating light and dark brown pigmented layers on cross-section. Chemically these stones contained low levels of cholesterol, with high levels of bilirubin and calcium. Subsequent infrared spectroscopy analysis showed that calcium bilirubinate and calcium palmitate were the only calcium salts present. Calcium palmitate was prominent in the light brown layers. A morphological and chemical comparison with gallbladder stones showed that bile duct "stasis stones" were similar in morphological and chemical composition to the brown pigment gallbladder calculi. However, they were distinct from most gallbladder stones, indicating that primary bile duct calculi have an aetiology that is different to 90% of gallbladder calculi. Primary bile duct calculi were observed to occur with or without the presence of a gallbladder, and more interestingly, in the bile duct of two patients with cholesterol gallbladder stones. Bile duct bile of patients with primary choledocholithiasis were always moderately to profusely infected and with abundant calcium bilirubinate precipitation. Moreover, this study has shown that PBDS chemical analyses profiles were consistent and correlated well with their defined morphology. Consequently, PBDS may be accurately identified at the time of operation by morphology. An important aetiological factor would appear to be infection, which would seem to promote bile duct bile stasis and eventual stone growth. PMID- 1931790 TI - Should benign hepatic tumours be excised? PMID- 1931791 TI - Brian Blundell Boycott. PMID- 1931792 TI - Light has many meanings for cephalopods. AB - The uses of light for cephalopods living at various depths are described. Aphakic apertures are shown in the eyes of Amphitretus and bolitaenids. In cirrate octopods, the eye is an open cup without lens and the retinal rhabdoms are disorganized. The photosensitive vesicles of cephalopods are extraocular receptors present either in the mantle or on the head. In some mesopelagic forms, they serve to compare the downwelling light with that emitted by the animal's own photophores, thus allowing regulation of counterillumination. In bathypelagic species, the photosensitive vesicles are very large and may serve to ensure reproduction at great depths. Some of the uses of the paired eyes in shallow water species are discussed. The mechanism for visual learning consists of a system for allowing many possible combinations of the output from numerous feature detectors. This begins with a set of columns in the optic lobes, followed by a tangential system. Outputs from the optic lobe lead to either attack or retreat: a third output leads to a memory system of four matrices allowing for interaction among the visual signals and between them and signals of taste or pain. These matrices allow conjunctive interaction between particular sets of signals and the setting up of memories ensuring appropriate responses. The matrices may be considered as analogous with those of the mammalian hippocampus. They include re-excitation among themselves and with the optic lobes. The tactile memory apparatus of the octopus has four similar lobes and also makes use of the four lobes of the visual system. These are therefore striking examples of adaptive networks allowing learned reactions by statistical selection among numerous channels. The anatomy, function, and generalizing powers of these networks emerged from Boycotts's early work, whose significance for computation can now be appreciated. PMID- 1931793 TI - Brian Boycott festschrift. June 14-16, 1990, Harvard University. PMID- 1931795 TI - Some visual and neurochemical correlates of refractive development. AB - Increasing evidence indicates that the retina takes part in the postnatal regulation of eye growth, functioning in this respect to minimize refractive error. The evidence derives both from clinical observations in man and from experiments in animals. The discovery that visual form deprivation leads to an axial overgrowth of the eye and to myopia has opened the way to many current research initiatives. Neurochemical and immunocytochemical experiments in chick and monkey suggest that definable retinal neurons participate in the regulatory pathway controlling eye growth. The most comprehensive data presently implicate dopaminergic amacrine cells. Other important issues to be addressed include the relevance of an intact connection to the central nervous system and the precise retinal mechanism by which eye growth is regulated. PMID- 1931794 TI - The organization of dopaminergic neurons in vertebrate retinas. AB - A survey of the shapes of dopaminergic (DA) neurons in the retinas of representative vertebrates reveals that they are divisible into three groups. In teleosts and Cebus monkey, DA cells are interplexiform (IPC) neurons with an ascending process that ramifies to create an extensive arbor in the outer plexiform layer (OPL). All other vertebrates studied, including several primate species, have either DA amacrine cells or IPCs with an ascending process that either does not branch within the OPL or does so to a very limited degree. DA neurons of non-teleosts exhibit a dense plexus of fine caliber fibers which extends in the distal most sublamina of the inner plexiform layer (IPL). Teleosts lack this plexus. In all vertebrates, DA cells are distributed more or less evenly and at a low density (10-60 cells/mm2) over the retinal surface. Dendritic fields of adjacent DA neurons overlap. Most of the membrane area of the DA cell is contained within the plexus of fine fibers, which we postulate to be the major source of dopamine release. Thus, dopamine release can be modeled as occurring uniformly from a thin sheet located either in the OPL (teleosts) or in the distal IPL (most other vertebrates) or both (Cebus monkey). Assuming that net lateral spread of dopamine is zero, the fall of dopamine concentration with distance at right angles to the sheet (i.e. in the scleral-vitreal axis) will be exponential. The factors that influence the rate of fall-diffusion in extracellular space, uptake, and transport--are not yet quantified for dopamine, hence the dopamine concentration around its target cells cannot yet be assessed. This point is important in relation to the thresholds for activation of D1 and D2 dopamine receptors that are found on a variety of retinal cells. PMID- 1931796 TI - The design of the optic nerve in fish. AB - Fish have large eyes, with short optic nerves that are continually flexed by compensatory eye movements during swimming. Here, I review the tissue construction of the fish optic nerve, to see how the glia and axons are adapted to withstand these mechanical stresses, which are not normally encountered by CNS tissue within the skull. As in other lower vertebrates, the optic nerve astrocytes are highly unusual: their intermediate filaments are composed of cytokeratins (Giordano et al., 1989), not GFAP. Their processes are linked together by desmosomes, forming thin transverse lace-like partitions, placed at quasi-regular intervals longitudinally (Maggs & Scholes, 1990). This accordion like arrangement is interpreted as providing a flexible tissue-skeleton for the optic nerve. A new observation is that the optic axons run in coherent parallel waves. This pattern, which is complementary to that of the astroglia, reversibly accommodates limited axial stretches. The waves are equivalent to those underlying the optical banding of Fontana (1781) in peripheral nerves, but wavelength (30 microns) and amplitude (5 microns) are about an order of magnitude less, reflecting the much smaller average size of the optic axons. The pattern also occurs in mammals, and may be restricted to the visual pathway: if present elsewhere in the CNS, nerve-fiber waves are inconspicuous at best. In fish, the astroglial partitions occur in register with the waves, suggesting that steric interactions between developing axons and glia may help to establish, or stabilize, the regular longitudinal spacing. This may have functional as well as mechanical implications, since the astrocytes form perinodal associations and their pattern is one which strongly clusters the nodes of Ranvier. PMID- 1931797 TI - Neuronal basis for parallel visual processing in the fly. AB - Behavioral and electrophysiological studies of insects demonstrate both spectrally independent and chromatically dependent behaviors and interneurons. This account describes the neuroanatomical identification of two parallel retinotropic subsystems, one supplying descending channels to spectrally independent neck and flight motor circuits, the other supplying polychromatic channels to neuropils associated with leg motor circuits in the thoracic ganglia. In the compound eye, two classes of photoreceptors contribute to each of several thousand sampling units. High-sensitivity, chromatically uniform short-axon photoreceptors (R1-R6) supply the lamina's external plexiform layer and are presynaptic to L1, L2 efferents. These project in parallel with a second system of trichromatic long-axon receptors and the L3 efferent. Both pathways supply columns of the medulla, equal in number to ommatidia. Golgi and cobalt-silver impregnation demonstrates that neurons from the medulla diverge to two deeper regions, the lobula plate and lobula, the former a thin tectum of neuropil dorsal to the more substantial lobula. Layer relationships between medulla neurons and their afferent supply suggest that the lobula plate and lobula are each supplied by one or the other, but not both, of the two parallel subsystems. Independence of the two parallel pathways is suggested by ablation of the photoreceptor layer leading to selective degeneration of the motion-sensitive lobula plate neuropil. In addition, octets of small-field neurons associated with the R1-R6/L1, L2 pathway give rise to synaptic complexes with motion-sensitive neurons of the lobula plate. A variety of behavioral and electrophysiological studies provide supporting evidence that certain insects possess parallel visual pathways comparable to the magnocellular and parvocellular subsystems of primates. PMID- 1931798 TI - The rod circuit in the rabbit retina. AB - Mammalian retinae have a well-defined neuronal pathway that serves rod vision. In rabbit retina, the different populations of interneurons in the rod pathway can be selectively labeled, either separately or in combination. The rod bipolar cells show protein kinase C immunoreactivity; the rod (AII) amacrine cells can be distinguished in nuclear-yellow labeled retina; the rod reciprocal (S1 & S2) amacrine cells accumulate serotonin; and the dopaminergic amacrine cells show tyrosine-hydroxylase immunoreactivity. Furthermore, intracellular dye injection of the microscopically identified interneurons enables whole-population and single-cell studies to be combined in the same tissue. Using this approach, we have been able to analyze systematically the neuronal architecture of the rod circuit across the rabbit retina and compare its organization with that of the rod circuit in central cat retina. In rabbit retina, the rod interneurons are not organized in a uniform neuronal module that is simply scaled up from central to peripheral retina. Moreover, peripheral fields in superior and inferior retina that have equivalent densities of each neuronal type show markedly different rod bipolar to AII amacrine convergence ratios, with the result that many more rod photoreceptors converge on an AII amacrine cell in superior retina. In rabbit retina, much of the convergence in the rod circuit occurs in the outer retina whereas, in central cat retina, it is more evenly distributed between the inner and outer retina. PMID- 1931799 TI - Alpha ganglion cells in mammalian retinae: common properties, species differences, and some comments on other ganglion cells. AB - A specific morphological class of ganglion cell, the alpha cell, was first defined in cat retina. Alpha cells have since been found in a wide range of mammalian retinae, including several orders of placental and marsupial mammals. Characteristically, they have the largest somata and a large dendritic field with a typical branching pattern. They occur as inner and outer stratifying subpopulations, presumably corresponding to ON-center and OFF-center receptive fields. In all species, alpha cells account for less than 10% of the ganglion cells, their somata are regularly spaced, and their dendritic fields evenly and economically cover the retina in a mosaic-like fashion. The morphology of alpha cells and many features, both of single cells and of the population, are conserved across species with different habitats and life-styles. This suggests that alpha cells are a consistent obligatory ganglion cell type in every mammalian retina and probably subserve some fundamental task(s) in visual performance. Some general rules about the construction principles of ganglion cell classes are inferred from the alpha cells, stressing the importance of population parameters for the definition of a class. The principle, that a functionally and morphologically homogeneous population should have a regular arrangement and a complete and even coverage of the retina to perform its part in image processing at each retinal location, is especially evident across species and across ganglion cell types. PMID- 1931800 TI - Cone bipolar cells and cone synapses in the primate retina. AB - Primate retinal bipolar cells synapsing with two adjacent cones (2C bipolars) are further described. Their synaptic contacts are either as the central (invaginating) component of the cone triads or as basal (flat) contacts on the membrane of the cone pedicle base. Correspondingly, their axons end either in the b (inner half or in the a (outer) half of the inner plexiform layer. The shape and size of the axon terminals of 2C bipolars are indistinguishable from those of adjacent midget bipolars. Therefore 2C bipolars, like midget bipolars, probably synapse with midget ganglion cells. Two C bipolars have not been identified as connected to foveal cones. But they are not restricted to the retinal periphery, as has previously been supposed, since they occur, mixed with midget (single cone) bipolars, throughout all parts of the retina from about 2.5 mm to at least 10.0 mm from the fovea. It is likely that 2C bipolars are a variant of the midget bipolars; and that they contact some members of the same population of cones, instead of the midgets. This paper briefly reviews, and raises some new, problems concerning our current understanding of the synaptic connectivity patterns of the midget, 2C, and diffuse cone bipolar cells. PMID- 1931801 TI - Anatomical pathways for color vision in the human retina. AB - The major neurons and neural circuits that are involved in the transmission of color signals through the human retina to produce the color and spatially opponent P cell or midget ganglion cell responses are described. The older findings of single cone to midget bipolar connectivity is reviewed, and the single midget bipolar cell to midget ganglion cell connectivity as revealed by a recent serial section electron microscope study is described in detail. Our present knowledge concerning the discrimination of the blue-cone subtype from the other longer wavelength cones in the human at the outer plexiform layer is summarized, and our most recent findings concerning horizontal cell connectivity to the different spectral types of cones are discussed. Finally, a hypothetical pathway is proposed for color-opponent surrounds of midget ganglion cells using both horizontal cells at the outer plexiform layer and amacrine cell pathways at the inner plexiform layer. PMID- 1931802 TI - Red-green interactions in the spectral sensitivity of primates as derived from ERG and behavioral data. AB - Different techniques were used to manipulate the inhibitory interaction between the red and green photoreceptors (R and G cones) of rhesus and human primates. The response techniques that were used were the corneal electroretinogram (ERG) and psychophysical increment-threshold spectral sensitivity functions. Red-green opponency, as measured by the depth of the notch at 580 nm, is removed by intravitreal injection of bicuculline but not by strychnine. Therefore, red-green opponency is mediated by GABA and not glycine. The depth of the notch is dependent upon stimulus size. Between 30' and 15' test light diameters, this sign of red-green opponency disappears. Psychophysical increment thresholds are shown to produce the notch while decrements do not and intravitreal APB is shown to reduce the notch, evidence that red-green opponency is carried by the "ON" and not the "OFF" bipolar pathways of the retina. Red and green annuli are shown to selectively reduce red and green inhibition, as though there were selective reduction of the surround response in center-surround organized red-green receptive fields. PMID- 1931803 TI - Application of automated MRI volumetric measurement techniques to the ventricular system in schizophrenics and normal controls. AB - As an initial approach to computer-automated segmentation of cerebral spinal fluid (CSF) vs. brain parenchyma in MR scans, and the transformation of these data sets into volumetric information and 3D display, we examined the ventricular system in a sample of ten chronic schizophrenics with primarily positive symptoms and 12 normal subjects. While no significant differences were noted between groups on volumetric measures of ventricular brain ratio or lateral ventricle size, normals showed a pattern of left greater than right lateral ventricular volume asymmetry not present in the schizophrenics. Within the schizophrenic group, departure from the normal left greater than right pattern was highly correlated with thought disorder. PMID- 1931804 TI - Frontal and callosal neuropsychological performances in schizophrenia. Further evidence of possible attention and mnesic dysfunctions. AB - Some level of frontal and callosal dysfunction has been reported in patients with schizophrenia. In the present study 68 normal controls and 117 schizophrenic patients were administered the Wisconsin Card Sorting Test (WCST), which involves the function of the frontal areas, and the Auditory Comprehension Test (ACT) which involves the corpus callosum and to a lesser degree attention and mnesic mechanisms. WCST correctly discriminated 69.8% of schizophrenics and 74.2% of controls, ACT 86.7% of schizophrenics and 90.2% of controls. Moreover, schizophrenics correctly classified by the WCST performed more poorly than schizophrenics incorrectly classified by the WCST on the related ACT indices for the attention and mnesic mechanisms. There were no differences in present age, age at onset, duration of the illness, diagnostic subtype and course of the disease between correctly and incorrectly classified schizophrenics by the WCST and the ACT. These data indicate a prevalent malfunctioning of attention and mnesic mechanisms in schizophrenia. Finally there seems to be no relationship between these neurofunctional abnormalities and demographic and clinical characteristics of the disease. PMID- 1931805 TI - Cognitive functioning and positive and negative symptoms in schizophrenia. AB - The present study examined schizophrenics' performance on a variety of cognitive measures in order to explore the relationship between schizophrenic symptoms and cognitive performance. The Wechsler Adult Intelligence Scale and a battery of neuropsychological tests, developed at the Montreal Neurological Institute, were administered to 38 acutely ill, hospitalized schizophrenics. Patients were diagnosed using DSM III criteria. Negative symptoms were assessed with the SANS and positive symptoms with the SAPS. Both the cognitive tests and the symptom rating scales were re-administered to this sample at a 6 month follow-up period. Analyses revealed that, at both time periods cognitive deficits were more likely to be associated with high negative symptom ratings than with positive symptoms. Only certain tests showed significant improvement at the follow-up period. Furthermore, improved cognitive functioning was related to an improvement in positive, but not negative, symptoms. PMID- 1931806 TI - Specificity of smooth pursuit eye movement and visual fixation abnormalities in schizophrenia. Comparison to mania and normal controls. AB - Smooth pursuit eye movements (SPEM) were assessed in 30 schizophrenic patients, 12 lithium-free manic patients, and 20 normal controls. Compared to schizophrenic patients, manic patients evidenced less SPEM impairment in an attention enhancing, sinusoidal target motion condition and had superior performance during a visual fixation condition. SPEM and visual fixation dysfunctions may be more common in schizophrenic than in acutely manic patients, even when the latter are characterized by marked attentional dysfunction, poor interepisode psychosocial functioning, and psychosis. PMID- 1931807 TI - Two modes of central gaze fixation maintenance and oculomotor distractibility in schizophrenics. AB - Distractibility defined operationally as a lack of stability in central-gaze fixation has been studied using two different oculomotor tasks that require the suppression of reflexive saccades triggered by the sudden appearance of novel, peripheral visual stimuli. In the first task ('Instructed'), maintenance of central gaze fixation was based on verbal instruction, whereas, in the second task ('Non-Instructed'), it was based upon a foveating mechanism maintained by sensory stimulation during the performance of a categorization task. 15 schizophrenics and 20 healthy control subjects were tested in the two tasks. Schizophrenics made more saccades than control subjects in the Instructed task only. The Instructed task saccade rate correlated significantly with scores on neuropsychological tests sensitive to frontal lobe dysfunction. Because the type of deficit observed in schizophrenics resembled that previously seen in patients with unilateral lesions of the ventrolateral convexity of frontal lobe, frontal lobe dysfunction was proposed as underlying the high task-specific distractibility of schizophrenics. PMID- 1931808 TI - Time course and clinical predictors of treatment response in schizophrenia. AB - The severity of schizophrenic symptoms was examined in 50 male chronic patients while neuroleptic free for at least 3 weeks and during 6 weeks of treatment with haloperidol. The results suggested that 50% of the improvement associated with haloperidol administration occurred by the end of the first treatment week and that early improvement, at both 1 and 4 weeks of treatment, was predictable from drug-free symptom severity. There was a negative correlation between week 1 improvement and improvement during the next 3 weeks of treatment, suggesting that medication response is not linear. Finally, dose increases after 4 weeks of treatment with 20 mg of haloperidol did not lead to any clinical improvement. These results are discussed in terms of their implications for selecting chronic schizophrenic patients who will and will not benefit from medication treatment. PMID- 1931810 TI - The role of serotonin in schizophrenia. New findings. PMID- 1931809 TI - Prevalence and stability of social skill deficits in schizophrenia. AB - The prevalence of social skill deficits in schizophrenia was examined by comparing patients assessed over a 1 year period with a group of non-patient controls recruited from the community. Social skills were assessed using a role play test and were considered deficient when they were below the range of the control sample. Approximately 50% of the patients were consistently unskilled over the one year, whereas 11% were consistently skilled. Deficits in specific social skills were relative rare. Consistent deficits were present for only one of six specific skills: 14% of the patients were consistently less appropriate in their conversational turn-taking (Meshing) than the controls. Patients' social skills were relatively stable over time. The implications of these results for the assessment and remediation of social skill impairments in schizophrenia are discussed. PMID- 1931811 TI - Obstetric complications in schizophrenic parents. PMID- 1931812 TI - Induction of Ly-6A/E expression by murine lymphocytes after in vivo immunization is strictly dependent upon the action of IFN-alpha/beta and/or IFN-gamma. AB - Ly-6A/E is a phosphatidylinositol-linked membrane protein which mediates murine T and B cell signalling. IFN-gamma, IFB-alpha/beta, LPS, and IL-4 have all been reported to induce or upregulate Ly-6A/E by normal lymphocytes. Since no systematic study has addressed the stimulant selectivity of Ly-6A/E expression by murine lymphocytes nor investigated its induction and regulation during primary in vivo immune responses we analyzed in vitro Ly-6A/E expression after murine stimuli and during a number of distinct in vivo immunizations. We show that LPS induces B cell Ly-6A/E in vitro by stimulating the release of IFN-alpha/beta by 'contaminating' adherent cells. In the presence of anti-IFN-gamma + anti-IFN alpha/beta antibodies, no Ly-6A/E was induced upon addition of multiple cytokines, including IL-4, or mitogenic doses of anti-Ig antibody. Furthermore, IFN-gamma-containing, CD4+ T cell (Th1) supernatants potently induced Ly-6A/E by murine B cells whereas IL-4-containing (Th2) supernatants were either weak or ineffective; anti-IFN-gamma + anti-IFN-alpha/beta inhibited Ly-6A/E induction by both Th1 and Th2 supernatants. Immunization of mice with Brucella abortus or poly (I).poly (C) resulted in induction of Ly-6A/E expression by virtually all B and T cells, whereas injection of G alpha M delta led to peak induction of Ly-6A/E by approximately 50% of both B and T cells. Lymphocytes from mice infected with the nematode parasites Nippostrongylus brasiliensis or Heligmosomoides polygyrus expressed no Ly-6A/E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931813 TI - Biased amino acid distributions in regions of the T cell receptors and MHC molecules potentially involved in their association. AB - We have analysed, in the context of the available structural information, the frequency of occurrence of different amino acids in functional regions of both the class I MHC antigens and of the TCR alpha and beta chains. We found that in class I MHC molecules, charged residues are found frequently among those which are presumably dedicated to interactions with the TCR, while the aromatic side chain residues are found more in the interior of the groove. In the TCR, the Asn residue appears with high frequency in all the CDR equivalents. The TCR CDR3s of both alpha and beta chains are particularly rich in Gly, whereas the CDR1 and CDR2 loops exhibit strong biases in favour of charged residues. Accordingly, the interactions between the MHC molecule and the peptide antigen appear to be essentially mediated by hydrophobic interactions and hydrogen bonding, while electrostatic interactions between charged residues might be important in the association of TCR and MHC molecules. The observation that each CDR1 and CDR2 is biased towards a particular set of amino acids, taken together with the nature of the protruding residues on the MHC helices, allows us to propose, in the frame of a molecular model of the MHC-TCR complex, several plausible configurations. PMID- 1931814 TI - Non-consensus DNA sequences function in a cell-type-specific enhancer of the mouse class II MHC gene A alpha. AB - Class II MHC proteins play central roles in controlling immune cell repertoire and responses. These roles depend on precise regulation of the level and cell type specificity of class II gene expression. Instances of both coordinate and non-coordinate regulation of the multiple class II genes have been described. A 1.3 kb region of the class II MHC gene A alpha has previously been shown to activate transcription in a cell-type specific fashion that correlated with the expression of A alpha. The mouse A alpha gene differs from other class II MHC genes in that its conserved X region also contains the CRE/ATF DNA motif TGACGTCA. Substitution mutations were introduced into the 1.3 kb region such that the CRE/ATF (X2) motif was altered, but not the adjacent X1 or Y box motifs. Controls confirmed that these mutations eliminated the binding of nuclear proteins to the CRE/ATF motif and reduced transcriptional activity as much as mutation of the Y box. In addition, a new positive transcription element was identified far upstream from the conserved X-Y region, centered on position -970. The sequence of this region does not resemble previously described transcription elements or other MHC class II 5' flanking sequences. The activity of this element was absolutely dependent on the presence of the X-Y region. These data are most consistent with a model in which functionally important sequences unique to a single class II MHC gene can be intimately interposed between conserved MHC transcription elements, and non-consensus elements upstream from the conserved region contribute to control of A alpha. PMID- 1931815 TI - Murine interleukin 5 receptor isolated by immunoaffinity chromatography: comparison of determined N-terminal sequence and deduced primary sequence from cDNA and implication of a role of the intracytoplasmic domain. AB - The murine interleukin 5 receptor (IL-5R) was identified by utilizing an immobilized IL-5 and an immobilized monoclonal antibody against the murein IL-5R (designated H7 mAb). The H7 mAb immunoaffinity-purified materials from the extract of cell-surface radioiodinated T88-M cells (an IL-5-dependent early B cell line) using 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) were reacted with an immobilized IL-5 matrix. SDS-PAGE of the adsorbed fraction revealed a single band at approximately 60 kDa. The binding of the 60 kDa protein to the immobilized IL-5 matrix was inhibited by the excess IL-5. The CHAPS-extract depleted of the 60 kDa protein by the absorption with H7 mAb did not contain any IL-5 binding proteins. Immunoaffinity procedure provided a final 7400-fold purification, based on an estimation of the content of the 60 kDa protein (approximate purity: 20%) from the silver-stained pattern of SDS-PAGE. Actin was copurified with the 60 kDa protein at an approximate ratio of 1:1, suggesting that the intracytoplasmic domain of the IL-5R may interact with actin. Furthermore, soluble IL-5R (molecular mass: 50 kDa) was purified by the H7 mAb immunoaffinity chromatography. The purified soluble IL-5R was capable of inhibiting the binding of IL-5 to T88-M cells. Preparative SDS-PAGE followed by electroblotting onto a membrane permitted the determination of the N-terminal sequence of the IL-5R. The determined N-terminal sequence of the IL-5R and the deduced primary sequence from recently isolated cDNA were compared. PMID- 1931816 TI - Global warming and human health: does a real threat exist? PMID- 1931817 TI - Is the occurrence of some spontaneous mutations directed by environmental challenges? AB - Cairnsian mutations have been defined as nonrandom mutations that occur as specific and direct responses to environmental challenges. This article reviews the evidence for the occurrence of such mutations in Escherichia coli, and concludes that under conditions of prolonged, intense selection Cairnsian mutations occur at several loci, and include base substitution mutations, frameshift mutations, and mutations mediated by excision of mobile genetic elements. Cairnsian mutations occur in nondividing cells. They are thus time dependent, rather than replication-dependent. The process that produces Cairnsian mutations is so powerful that it can generate double mutations at rates (mutations per cell per day) that approach the rates of the component single mutations under identical conditions. Several mechanisms, including slow repair of mis-matched bases, mutagenic transcription, and a hypothetical "hypermutable" physiological state, have been proposed to explain the occurrence of Cairnsian mutations by an underlying random process, rather than by the instructional, or "directed" process originally proposed by Cairns. Recent evidence, however, argues strongly against all of those proposed mechanisms and leaves us without a viable model to explain this powerful, and potentially very important, process. PMID- 1931818 TI - Schistosomes, fibroblasts, and growth factors: how a worm causes liver scarring. AB - The traditional concept of tissue scarring as a static pathological endpoint has been replaced by the modern perspective of a potentially reversible process comprising a sequence of discrete biological events (cell recruitment and hyperplasia, excessive matrix production, and matrix degradation). Cytokines, including several produced by inflammatory cells, have been identified that specifically regulate these events. Research into the cellular and molecular biology of scar formation is motivated by clinical and basic scientific considerations. One model of fibrogenesis that is being studied in detail is the liver fibrosis associated with schistosomiasis. In this helminthic infection, the host's granulomatous inflammatory response to the parasite eggs apparently lead to scar formation. A novel lymphokine that is mitogenic for fibroblasts and is produced by CD4+ lymphocytes in the granuloma has been found in infected livers. Preliminary evidence for the existence of immunoregulatory mechanisms of fibrogenesis in this disease also has been obtained. The potential role of genetic determinants that may influence this process needs to be further studied. PMID- 1931819 TI - Stem cell mysteries. Workshop on Stem Cell Biology sponsored by the Programs in Molecular Medicine of the Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, USA, April 5-6, 1991. PMID- 1931820 TI - Proteins by design. The Sixteenth Annual Lorne Conference on Protein Structure and Function, Lorne, Victoria, Australia, February 10-14, 1991. PMID- 1931821 TI - Negative strand RNA viruses come of age. Negative Strand RNA Virus Transcription and Replication sponsored by the Fundacion Juan March, Madrid, Spain, April 22 24, 1991. AB - The recent development of several systems that facilitate manipulation of the nucleotide sequences of negative strand RNA viruses and examination of the effects of these changes in vivo has enabled great progress in the study of these fascinating organisms. Such studies are leading to a greater understanding of the role of viral nucleotide sequences and viral (and sometimes cellular) proteins in the control of negative strand RNA virus replication and transcription. This Fundacion Juan March Workshop provided an excellent opportunity for extensive discussion and exchange of ideas on just how far the research on these viruses has gone, and for contemplating the paths that future inquiries will take. PMID- 1931822 TI - Trans-dominant Tat mutants with alterations in the basic domain inhibit HIV-1 gene expression. AB - The Tat protein of the human immunodeficiency virus type 1 (HIV-1) is required for efficient viral gene expression. By means of mutational analyses, several domains of the Tat protein that are required for complete activation of HIV-1 gene expression have been defined. These include an amino-terminal activating domain, a cysteine-rich dimerization domain, and a basic domain important in the binding of Tat to the trans-activation response element (TAR) and in Tat nuclear localization. Recently, we described a mutation, known as delta tat, which resulted in a protein with a truncated basic domain. This protein had a "trans dominant" phenotype in that it inhibited wild-type Tat activation of the HIV-1 LTR. To further characterize the requirements for generating a Tat trans-dominant phenotype, we constructed a variety of Tat proteins with truncations or substitutions in the basic domain. A number of these proteins showed a trans dominant phenotype. These Tat mutants also inhibited activation of the HIV-1 LTR by a protein composed of Tat fused to the prokaryotic R17 (phage MS2) RNA-binding protein in which the R17 recognition element was inserted in the HIV-1 LTR in place of TAR. Thus, an intact TAR element was not required for this inhibition. We also studied the cellular localization of Tat and a trans-dominant Tat mutant by means of immunofluorescence staining with the use of antibodies reactive to different domains of the Tat protein. The results indicated that Tat becomes localized predominantly in the nucleus both in the presence and absence of the trans-dominant Tat construct, suggesting that the trans-dominant mutant does not inhibit Tat nuclear localization. These studies further define the requirements for the creation of trans-dominant Tat mutants, and suggest that the mechanism of trans-dominant Tat inhibition may be either the formation of an inactive complex between wild-type and mutant Tat or sequestration of cellular factors involved in regulating HIV-1 gene expression. PMID- 1931823 TI - Site-specific recombination promoted by a short DNA segment of plasmid R1 and by a homologous segment in the terminus region of the Escherichia coli chromosome. AB - A short DNA segment located in the kanamycin resistance region of plasmid R1 promotes site-specific recombination and plasmid maintenance. This segment has been reduced to 100 bp and subsequently to 44 bp without losing these properties. It can recombine with a similar segment located in the terminus region of the Escherichia coli chromosome. It is proposed that this recombination is responsible for the plasmid maintenance properties of the R1 segment. The chromosomal site has been isolated; it also shows site-specific recombination activity. Sequence homologies were also found with a phage site-specific integration locus in the chromosome of Xanthomonas campestris and with the plasmid ColE1 site-specific recombination locus. The recombinase required in all these systems is probably XerC, an E. coli enzyme acting on the cer site of plasmid ColE1 for the conversion of plasmid dimers to monomers. It is postulated that site-specific recombination in the terminus region of the chromosome intervenes in the partitioning of the two daughter chromosomes. PMID- 1931824 TI - Escherichia coli XerC recombinase is required for chromosomal segregation at cell division. AB - XerC is a site-specific recombinase of the bacteriophage lambda integrase family that is encoded by xerC at 3700 kbp on the genetic map of Escherichia coli. The protein was originally identified through its role in converting multimers of plasmid ColE1 to monomers; only monomers are stably inherited. Here we demonstrate that XerC also has a role in the segregation of replicated chromosomes at cell division. xerC mutants form filaments with aberrant nucleotides that appear unable to partition correctly. A DNA segment (dif) from the replication terminus region of the E. coli chromosome binds XerC and acts as a substrate for XerC-mediated site-specific recombination when inserted into multicopy plasmids. This dif segment contains a region of 28 bp with sequence similarity to the crossover region of ColE1 cer. The cell division phenotype of xerC mutants is suppressed in strains deficient in homologous recombination, suggesting that the role of XerC/dif in chromosomal metabolism is to convert any chromosomal multimers (arising through homologous recombination) to monomers. PMID- 1931825 TI - Response to adversity: molecular control of gene activation following genotoxic stress. AB - DNA damage leads to the induction of a variety of genes in mammalian cells. In this article we summarize recent works aimed at examining the specificity of the response and elucidating the molecular mechanisms by which DNA damage effects changes in gene expression. The response to DNA damage is controlled primarily at the level of transcription. Some of the inducible genes are members of the class of "immediate early" genes and encode transcriptional activators. These genes are induced by activators of protein kinase C, and most DNA damage-inducible genes are also activated by phorbol esters. Phorbol ester-response elements within the 5' region of several of these genes have been shown to play a role in mediating their induction in response to DNA damage. However, DNA damage-inducible transcripts that are not sensitive to phorbol esters have also been identified, indicating that there are additional mechanisms involved in such responses. Induction of many of the DNA damage-inducible genes appears to be dependent, at least in part, on protein kinases. These findings demonstrate considerable overlap between signal transduction pathways mediating cellular proliferation and the response to DNA damage. PMID- 1931826 TI - Thyroid hormone: half-sites and insights. Molecular Approaches to the Study of Thyroid hormone Action: a Keystone Symposium, Tamarron, CO, USA, March 8-14, 1991. AB - As is evident from the range of topics addressed in this review, T3 has important and interesting effects on virtually every biological system in higher organisms. Many of these effects are beginning to be understood at the molecular level, while others are not far behind. It is striking that the diversity of biological activities of T3 is reflected in a broad spectrum of molecular mechanisms. Even within the relatively circumscribed paradigm of receptor activation by hormone binding, a surprisingly large number of possible interactions and complications has been discovered. This richness of alternative interactions leads directly to complex and unanticipated regulatory possibilities. A major strength of this meeting was that it encompassed the broad range of T3 effects and thereby was able to provide something new for every attendee. From this perspective, it is easy to predict that study of T3 will continue to provide new and surprising insights into major biological questions for years to come. PMID- 1931827 TI - The ethereal web of chromosome structure and behavior. The First Carolina Conference on Chromosome Structure and Dynamics sponsored by the North Carolina Biotechnology Center, National Institute of Environmental Health Sciences, and the U.S. Environmental Protection Agency, Chapel Hill, NC, USA, May 2-4, 1991. PMID- 1931828 TI - High altitude termination. Regulation of Transcription Elongation and Termination: a Keystone Symposium, Keystone, CO, USA, April 19-25, 1991. PMID- 1931829 TI - HSFs and HSPs--a stressful program on transcription factors and chaperones. Stress Proteins and the Heat Shock Response, sponsored by Cold Spring Harbor Laboratory, Cold Spring Harbor, NY USA, April 29-May 2, 1991. PMID- 1931831 TI - Constitutive expression of FosB and its short form, FosB/SF, induces malignant cell transformation in rat-1A cells. AB - We have established Rat-1A cell lines constitutively expressing c-Fos and the two products of the fosB gene, FosB and its short form, FosB/SF. The expressed proteins in the different stable transfectants have been characterized by immunofluorescence and immunoprecipitation analysis. Our results demonstrate that constitutive expression of FosB, like the constitutive expression of c-Fos and, to a lesser extent, FosB/SF, results in cells that grow to increased saturation densities and have the ability to grow in an anchorage-independent manner. Most important is the finding that expression of these proteins augments the tumorigenic potential of Rat-1A cells. These results show that both forms of FosB have a stimulatory effect on cell proliferation. PMID- 1931830 TI - Embryonic lethality resulting from disruption of both N-myc alleles in mouse zygotes. AB - The N-myc gene is considered to play a major regulatory role in embryogenesis of the mouse because of its high expression in the organogenesis period and its encoding of nuclear proteins with DNA binding motifs. To elucidate the putative regulatory function of N-myc in embryogenesis, we undertook to inactivate this gene in ES cells. The N-myc alleles were disrupted in ES cells, line E14, by means of homologous recombination of targeting vectors that carry neomycin or hygromycin resistant genes. Homologous recombinants were obtained at the frequency of one in 6 x 10(5) electroporated cells. The inactivated N-myc alleles were transmitted through mouse germ lines. Crosses of heterozygous mice resulted in production of wild-type, heterozygous, and N-myc-null pups and fetuses at a ratio of 1:2:0, indicating embryonic lethality of the homozygotes. ES cells totally deficient in N-myc expression were also obtained by consecutive gene disruption with the use of the targeting vectors, demonstrating the non essentiality of N-myc expression in the stem-cell state. N-myc-null ES cells offer a valuable tool in chimera analysis to elucidate the requirement for N-myc function in embryogenesis. PMID- 1931832 TI - Genetic and physical mapping of the human cannabinoid receptor gene to chromosome 6q14-q15. AB - A cDNA encoding a G protein-coupled receptor that appears to mediate the behavioral effects of cannabinoids, the psychoactive ingredients of marijuana, has recently been cloned from rat cerebral cortex and expressed. We have now determined the genomic location of the human cannabinoid receptor gene (CNR) by a combination of genetic linkage mapping and chromosomal in situ hybridization. The segregation pattern of a CNR DNA polymorphism was analyzed in 508 individuals from two or three generations of 40 families. Linkage of CNR to chromosome 6 centromeric loci and to DNA markers on the long and short arms was detected. CNR was tightly linked to D6S27, which is known to be located at 6q (log10 odds ratio [lod score, Zmax] of 10.54 at a recombination fraction [theta] of 0.02). Close linkage was suggested between CNR and CGA, the locus for the alpha subunit of human chorionic gonadotropin (Zmax = 2.71 at theta = 0). Moreover, CNR was linked to the two markers 308/BamHI (theta = 0.14) and 308/TaqI (theta = 0.20) defining locus D6Z1, an extended, highly repetitive, and highly conserved sequence localized exclusively to centromeres of all chromosomes and enriched on chromosome 6. In situ hybridization using a biotinylated cosmid probe localizes the gene to 6q14-q15, thereby confirming the linkage analysis and defining a precise alignment of the genetic and cytogenetic maps. PMID- 1931833 TI - rhlB, a new Escherichia coli K-12 gene with an RNA helicase-like protein sequence motif, one of at least five such possible genes in a prokaryote. AB - A newly recognized gene we name rhlB, after RNA helicase-like genes, has been found in the 85-minute region of the Escherichia coli chromosome. This gene encodes protein sequence motifs similar to those known for "D-E-A-D box" gene products. Proteins in this gene family occur in eukaryotes as well as prokaryotes, and, as far as tested, have been found to participate in ATP dependent RNA helicase or RNA-dependent ATPase activities. The functions of these enzymes are poorly understood. In yeast, mutant phenotypes of various D-E-A-D genes suggest that they function in RNA splicing, processing, or translation. We find that rhlB is necessary for viability only in some genetic backgrounds. Conditional rhlB lethality is not complemented by another E. coli RNA helicase like gene (srmB). Using primers with homology to consensus sequences in D-E-A-D box proteins, we have recovered DNA fragments amplified from E. coli genomic DNA by polymerase chain reactions. Sequence analysis of these fragments suggests that E. coli possesses at least five RNA helicase-like (rhl) D-E-A-D box genes at widely separated chromosomal locations. The multiplicity of such genes in a prokaryote raises the possibility of important roles for the corresponding class of biologically widespread proteins. PMID- 1931834 TI - Synergism between two distinct elements of the HTLV-I enhancer during activation by the trans-activator of HTLV-I. AB - We have conducted functional studies of the enhancer elements of human T-cell leukemia virus type I (HTLV-I) using the human T-cell lines Jurkat and MOLT 4, which are negative for HTLV-I, and MT-2 and TL-Mor, which carry the proviral genome of HTLV-I. Two distinct elements have been implicated in function of the HTLV-I enhancer. One is the 21-base-pair (bp) core element that is responsible for trans-activation by the HTLV-I trans-activator p40tax and that has the ability to bind to cyclic-AMP responsive element binding factor (CREB)-like factor(s). The other is a region interposed between the 21-bp elements. In this study we demonstrate that a subfragment (C26) in the region between the 21-bp elements is involved in trans-activation by p40tax, possibly through binding to an NF-kappa B-like nuclear factor or factors. Formation of the protein-DNA complex with the C26 subfragment was positively affected by p40tax. The C26 element conferred partial responsiveness to p40tax when linked to one copy of the 21-bp element that, by itself, showed little activation in response to p40tax. However, the C26 element alone, even when repeated, could not be activated by p40tax, unlike other NF-kappa B-binding elements. In contrast, the C26 element itself was profoundly activated upon stimulation with 12-O-tetradecanoylphorbol 13-acetate. These findings therefore suggest that the HTLV-I enhancer contains multiple functional elements, including binding sites for at least CREB- and NF kappa B-like factors, which synergistically cooperate in activation of the HTLV-I enhancer in response to p40tax. Our results also demonstrate that TPA-dependent activation of the HTLV-I enhancer may be mediated through the C26 element. PMID- 1931835 TI - Expressing moral outrage. PMID- 1931836 TI - Characteristics and prognosis of extradural hematomas in children. AB - This is a report on 31 children with operated extradural hematoma. The aim of the study was to elucidate the characteristics of extradural hematoma in childhood and the different clinical pattern and outcome compared to adults. For that reason the charts of the patients seen at the Department of Surgery of the Children's University Hospital Zurich between 1972 and 1990 have been revised. Follow-up criteria were recorded according to the Glasgow Outcome Scale. Most hematomas have been provoked by minor injuries and almost all children presented with at least one typical clinical sign. Associated intracranial injuries have been found in four patients, while two were polytraumatised. 30 of the 31 patients survived. One patient died of malignant brain edema. The mean range of follow-up was seven years. 28 patients had a "good recovery", "moderate disability" and "severe disability" was found in a patient one each. Our results demonstrate that the long-term outcome in children with extradural hematoma is far better than in adults regarding survival as well as quality of life. The causes may be minor traumas with fewer associated lesions and presentation with typical clinical findings and therefore early diagnosis and treatment. PMID- 1931837 TI - Cranioplasty for acquired skull defects in children--a comparison between autologous material and methylmethacrylate 1974-1990. AB - The authors report on their experiences with 21 patients with skull defects which were closed by polymethylmethacrylated plates (PMMA) from 1974 to 1990 at the University Children's Hospital in Zurich and the "Gemeinschaftspraxis fuer Kinderchirurgie". The results were compared with 15 cases treated by autologous grafts. Because of false indication, one case of PMMA-plasty led to an infected fistula. Otherwise no adverse reactions were noted. Three of the 15 cases with autologous grafts showed resorption. Polymethylmethacrylate is an excellent agent for skull reconstruction. The simple procedure, shorter OP time, and lack of pain or disfigurement due to a donor site signify a great advantage to this method. PMID- 1931838 TI - Osteocranioplasty of calotte defects with autoplastic rib segments in children. AB - Calotte defects that are larger than 3-5 cm require stable plastic reconstruction. Osseous regenerations take place at the connective tissue bone of the calotte if the dura is intact. Even large defects may be considerably reduced in this way within 2 or 3 years. Hence, indications must be critically reconsidered on a long-term basis. Autoplastic grafting of a rib segment has been known from the beginning of the present century. It has many advantages. Our approach, experience and results are presented. PMID- 1931839 TI - Indication and procedure of the operative treatment of benign bone cysts in children and adolescents. AB - In 2-3 reviews 30 patients with non ossifying fibroma and 31 patients with a solitary bone cyst were examined to evaluate the prognosis of these diseases. It has been shown that the cure rate of non ossifying fibromas of 95% and solitary bone cysts of 70% is extraordinarily good and does not depend on the treatment that has been realized. For that reason, the indication for operative treatment must be differentiated: Non ossifying fibromas should be left to spontaneous healing. Solitary bone cysts in the upper limb should be treated by puncture only when they show great activity, otherwise they can be left to spontaneous healing, too. In the lower limb active cysts with or without fracture should be operated, while inactive cysts should to be cured by puncture only. PMID- 1931840 TI - Hematogenous calcaneal osteomyelitis in children. AB - Heel pain is a frequent complaint in children due to intensive school and leisure time sports. Heel pain accompanied by inflammatory signs has to be considered as osteomyelitis until the opposite is proven. From 1980 to 1989, twenty children were treated for acute or subacute osteomyelitis of the calcaneus (OMC) at the Department of Pediatric Surgery of the Children's Hospital of Lucerne. The schema of investigation comprising laboratory work-up, x-rays, scintiscanning and aspiration of the focus makes quick and accurate diagnosis possible. Exogenous osteitis of the newborn and calcaneal apophysitis in children must be differentiated; this is a prime consideration. Treatment includes surgical interventions (curettage, drainage) and long-term antibiotics. The course of the disease can be shortened, complications become avoidable and the rate of recurrence is diminished. PMID- 1931841 TI - Reconstruction of skin and soft-tissue defects in crush-injuries of the lower leg in children. AB - Severe crush injuries with open comminuted fractures of the lower extremity often result in extensive tissue loss. In such a situation early free microsurgical tissue transplantation offers most effective possibilities of treatment. Among others, two of the most eminent advantages of free microsurgical tissue transplantation are: 1. The possibility of tissue replacement which cannot be achieved by traditional procedures such as functional muscle transplantation or the replacement of extremely extensive tissue loss; moreover immediate or early bone coverage by well vascularized soft-tissue is most effective in the prevention of infection. 2. In many cases complete reconstruction can be achieved by a one-stage-procedure: this decreases the morbidity considerably. These advantages are demonstrated by clinical cases, where we used free microsurgical tissue transplantation. PMID- 1931842 TI - Results of extended craniectomy including supraorbital advancement in premature coronal and frontal craniosynostosis. AB - Between 1982-1989 an extended craniectomy including supraorbital advancement was performed in 27 infants. Age ranged from 2.5 to 10 months (median 4.5 months). Six had a premature synostosis of the frontal suture, 11 a monolateral synostosis of the coronal suture and 10 a bilateral coronal synostosis. Eighty per cent had an excellent or good result. The amount of remodelling, as measured by the orbital roof angle, showed a tendency to normalisation of the anterior fossa in the lateral projection 3-4.5 months following surgery. In some of the infants the neurological signs and psychomotor development were ameliorated by the operation. But, in monolateral cases of coronal synostoses a squint of various types was observed more frequently. PMID- 1931843 TI - The transthoracic hiatoplasty for cases of non-operable gastroesophageal reflux. AB - After surgery in the upper abdomen is performed, conditions may develop prohibiting transabdominal repair of gastroesophageal reflux. The transthoracal hiatoplasty after L. Braun does not in all cases eliminate the reflux; it cures, however, the ulcers as well as the esophagitis. PMID- 1931844 TI - Is intestinal lengthening effective in treating extreme short bowel syndrome? AB - Our report concerns a child with short bowel syndrome who had 20 cm of small intestine distal to the pylorus (duodenum and jejunum) which remained after subtotal intestinal resection; the resection was necessitated by intrauterine volvulus with intestinal necrosis as a result of gastroschisis. In addition, only 25 cm of the colon remained. Despite continuous enteral nutrition with a semi elementary diet and conservative therapy, it was not possible to provide within six months at least occasionally half of the caloric intake required on an enteral basis. In such cases treatment is usually discontinued. As final alternative to a small intestine transplantation, we conducted an operation to lengthen the intestine (method according to Bianchi) when the patient was 8 months old. The massively dilatated jejunum section of the intestine was lengthened from 20 cm to 37 cm. Postoperatively enteral caloric intake could be increased from 11 kJ/kg/m to 20 kJ/kg/m. Unfortunately, at 14 months of age, the child died from hepatobiliary complications arising from aggravation of the cholestasis and acidosis. This case shows, nevertheless, that intestinal lengthening had a positive influence on intestinal resorption. PMID- 1931845 TI - Synovial chondromatosis of the knee joint: a rarity during childhood. AB - Synovial chondromatosis is a rare disease, especially in children. We report on a 12-year old girl who suffered twice a knee trauma. She then developed an arthritis of her right knee joint and finally showed all signs of synovial chondromatosis arthroscopically. Treatment consisted of removal of loose as well as stalked chondromatous bodies by means of arthroscopy. According to Milgram (1975) the evolution of the disease progresses through three stages, starting with synovial metaplasia producing chondromas which are then shed into the joint. Kay, Freemont and Davies (1989) doubt this theory. PMID- 1931846 TI - Traumatic spinal cord injury: unusual recovery in 3 children. AB - We report on 3 children with traumatic spinal cord injury. All of them had normal x-rays of the vertebral column. There were no abnormalities of the spinal cord in myelography or magnetic resonance imaging. Although these situations are often associated with a poor neurological prognosis, we observed very unusual recoveries in these 3 cases. PMID- 1931847 TI - Cholestasis caused by biliary botryoid sarcoma. AB - A 4-year-old boy with a short history of jaundice and hepatomegaly was studied by endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). A large obstructing choledochal tumour was found at the level of cystic duct insertion and at surgery, a botryoid sarcoma was removed. Subsequent cytotoxic therapy was complicated by persistent dilatation of the extrahepatic bile ducts which necessitated eventual excision. There was no evidence of persistent tumour. PMID- 1931848 TI - Association of hiatus hernia with postero-lateral diaphragmatic hernia (Bochdalek's hernia). AB - A boy with hiatus hernia following the repair of the left postero-lateral diaphragmatic hernia (Bochdalek's hernia) was reported. At the age of one month, the repair of Bochdalek hernia was performed with transabdominal approach. At that time the stomach was located in the normal position. Eight days after the repair he developed vomiting and hiatus hernia was revealed by barium esophagram. Antireflux surgery was required because there was no response to the conservative management for two months. Esophageal pH study and manometric study were very useful for the diagnosis of hiatus hernia or GER and the evaluation of antireflux surgery. PMID- 1931849 TI - Pyloric obstruction with complicated pancreatic heterotopia. AB - A case of pyloric obstruction associated with pancreatic heterotopia is described in an 18-day old child. The association of several pathologic processes like acute pancreatitis and abscess formation in the heterotopic mass and the long term follow-up are the main points of interest in this report. PMID- 1931850 TI - Superior vesical fistula: a case report. AB - Variants of bladder exstrophy are rare developmental abnormalities. Only a few cases have been reported in the literature to date. A case of superior vesical fistula with split symphysis and dorsal chordee is presented. If associated anomalies are absent, diagnosis and management of these lesions are easy and have a good prognosis. The patient is usually continent after surgical correction. PMID- 1931851 TI - Rationale of treatment for Class II division 2 malocclusion. AB - Class II, division 2 malocclusion is a clinical entity which presents considerable difficulty in the provision of a stable treatment result. This article sets out the problems encountered, reviews teaching on the subject over a 20-year period and attempts to rationalize the current approach to treatment. The rationale presented shows the three-dimensional nature of the occlusal problem, and discusses the justification for expansion and proclination of lower incisors in relation to soft tissue influences and stability. The importance of correcting edge-centroid relationship and reducing inter-incisor angle is stressed. Non extraction therapy, with some lower arch expansion and incisor advancement, is recommended and the reasoning behind this is explained with a case example to illustrate the points involved. PMID- 1931852 TI - A study of adult orthodontic patients and their treatment. AB - This retrospective epidemiological study was undertaken to assess factors related to adult orthodontic treatment and to identify any associated trends. Case records of all patients (676) aged 18 years or over at the start of active orthodontic treatment at the Eastman Dental Hospital, London were examined. Variables associated with patients and their treatment (age, sex, source of referral, malocclusion, type of appliance, and interdisciplinary treatment including orthognathic surgery) were studied and the data analysed statistically. Findings revealed that the number of adult patients undergoing orthodontic treatment has increased significantly, especially since 1985. The age of the patients treated was also found to increase in recent years. The percentage of female patients (72 per cent) Class III malocclusions (21.6 per cent) and Class III skeletal bases (26.2 per cent) was higher than found in studies on children. Most of the treatments required fixed appliances and over half involved interdisciplinary treatment, with an increase in the percentage of orthognathic surgical cases. Surgery was significantly more common in males (P less than 0.01) and highly significantly associated with Class III malocclusions and skeletal III bases (P less than 0.001). Twenty-five per cent of adult patients were found to have had a previous course of orthodontic treatment though these patients were not significantly different from adult patients presenting for the first course of treatment. PMID- 1931853 TI - A restorative-orthodontic treatment approach in the older patient. AB - This report presents a case requiring a combination of restorative dentistry and orthodontic treatment in a mature adult patient. Occlusal splint and periodontal therapies were used initially. Orthodontic treatment combined the use of the occlusal splint and fixed appliance in the maxillary arch. Sectional fixed appliances were used in the mandibular arch. The final restorations were fixed- movable bridges in the mandibular arch and a removable tooth and mucosally borne prosthesis in the maxilla. Retention of the orthodontic result was provided by the fixed prostheses in the lower arch and the continued wear of a full coverage maxillary occlusal splint at night served to prevent relapse of the upper teeth. PMID- 1931854 TI - An evaluation of zirconium oxide brackets: a preliminary laboratory and clinical report. AB - A pre-production sample of zirconium oxide (ceramic) brackets was examined in this study. A laboratory investigation of the tensile/peel bond strength of the brackets was carried out using two light-cured adhesives (Prismafil and Heliosit) and one chemically-cured adhesive (Delphic). The mode of failure was also investigated using optical and scanning electron microscopy. The bond strengths achieved with Prismafil were statistically significantly (P less than 0.05) lower than Heliosit and Delphic between which no significant differences were found. All samples failed at the bracket-adhesive interface. A clinical test demonstrated the extreme ease of sliding along stainless steel and nickel titanium archwires, and revealed a low plaque adhesion. The principal disadvantage of these brackets appears to be their off-white highly opaque appearance which in addition to giving poor aesthetics may adversely affect bond strength with light-cured adhesives. PMID- 1931855 TI - A finite element study of canine retraction with a palatal spring. AB - The use of a removable appliance to retract a maxillary canine tooth into a first premolar extraction space is one of the most commonly performed orthodontic procedures. However, unwanted movements may occur, including excessive tipping, rotation, and flaring of the tooth. The present investigation by the use of a finite element model quantifies some of the initial stresses produced within the periodontal ligament when two obliquely directed forces are applied to a maxillary canine tooth. In simulating the action of a removable appliance it attempts to relate the stress patterns to the nature of the subsequent tooth movement. PMID- 1931856 TI - Forces produced by auxiliary torquing springs in the Begg technique. AB - Different designs of Begg torquing auxiliary have been tested to measure the forces produced at the apex of a tooth. Forces at the tooth surface ranged from 0.4 to 3.3 N, equivalent to 0.1-0.9 N at the root apex. PMID- 1931857 TI - The relationship and reproducibility of angle ANB and the Wits appraisal. AB - An analysis is presented of the errors and variations in the Wits analysis and the angle ANB, using computer simulation. The method is applicable to any index where the identification errors have been established for the points and planes used in its derivation. A standard deviation may be determined for the index produced and the statistical distribution of values for any number of observations. PMID- 1931858 TI - Familial posterior open bite: a primary failure of eruption. AB - Two sisters are presented in whom posterior open bites have developed. Orthodontic treatment was not successful in correcting this aspect of the malocclusion in the older sibling. The younger child developed the same defect, and consequently orthodontic treatment is not being considered. PMID- 1931859 TI - Orthodontic research in the United Kingdom: a status report from the dental schools. PMID- 1931860 TI - Trends in the number of active and discontinued orthodontic treatments in the general dental service. PMID- 1931861 TI - Abstracts of U.K. University orthodontic theses and projects: Part I. PMID- 1931862 TI - Optimization of the liposomes encapsulating a new lipopeptide CGP 31362 for efficient activation of tumoricidal properties in monocytes and macrophages. AB - The purpose of this study was to optimize a suitable liposomal carrier for CGP 31362, a new synthetic lipopeptide analogue of gram-negative bacterial cell walls. CGP 31362 was inserted into the membranes of different liposomes with different phospholipid composition. We determined the ability of these liposomes to activate tumoricidal properties in mouse peritoneal and bone marrow macrophages, and in human monocytes. The ideal liposome carrier for CGP 31362 consisted of phosphatidylcholine and phosphatidylserine in a 7:3 molar ratio. Subsequent to efficient binding and endocytosis, CGP 31362 in liposomes of this composition rendered mouse macrophages and human monocytes highly tumoricidal. Moreover, even in the absence of interferon-gamma, human monocytes released significant levels of tumor necrosis factor and interleukin-1. These data show that in a suitable liposomal carrier, the new synthetic lipopeptide in liposomes is a potent activator of tumoricidal properties in macrophages. PMID- 1931863 TI - Phase I trial of ImmTher, a new liposome-incorporated lipophilic disaccharide tripeptide. AB - A phase I clinical trial was conducted to evaluate the toxicology and biological activity of a new liposome-incorporated lipophilic disaccharide tripeptide, ImmTher. Twelve patients with advanced nonhematological malignant disease received 13 courses of therapy at dose levels of 200-1,200 micrograms/m2. A course of therapy consisted of once-weekly administration of the drug for 2-12 weeks. The major clinical toxicities observed were chills and hypotension. No renal, hepatic, cardiac, or hematological toxicity was observed. A small decrease in pulmonary diffusion capacity was observed. Biological activity was demonstrated by changes in plasma cytokine levels, changes in in vitro monocyte cytotoxicity, and by a decrease in tumor size. Improvement was observed in three of three patients with metastatic disease to the liver. Response in these three patients correlated with an increase in their tumor necrosis factor and neopterin levels compared with nonresponders. These preliminary indications of biological and clinical activity of a liposome-incorporated lipophilic disaccharide tripeptide in patients with advanced metastatic hepatic disease suggest a potential new therapeutic approach to this common problem. PMID- 1931864 TI - Induction of cytokine production from human monocytes stimulated with alginate. AB - Alginates are polysaccharides with gel-forming properties composed of 1,4-linked beta-D-mannuronic acid (M), alpha-L-guluronic acid (G), and alternating (MG) blocks. Alginate can be used as a matrix for implanted cells in vivo. In this study, we have examined the ability of alginates and their components to stimulate human monocytes to produce tumor necrosis factor-alpha, interleukin-6, and interleukin-1. Alginates stimulated the monocytes to produce high levels of all three cytokines. Low G alginates were approximately 10 times more potent in inducing cytokine production compared with high G alginates. The M-blocks and the MG-blocks, but not the G-blocks, stimulated the cytokine production. The results demonstrate that the mannuronic acid residues are the active cytokine inducers in alginates. PMID- 1931865 TI - Metastatic renal cell cancer: interleukin-2 toxicity induced by contrast agent injection. AB - We describe a clinical syndrome occurring after contrast medium injection in patients who previously received recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha 2A treatment for metastatic renal cancer. The clinical picture mimics many aspects of rIL-2-related systemic side effects. The patients were managed conservatively but the potential for severe manifestations can occur, requiring more intensive treatment. PMID- 1931866 TI - George Lyman Duff Memorial Lecture. Multifactorial etiology of hypercholesterolemia. Implications for prevention of coronary heart disease. AB - This review underlines the concept that multiple factors are responsible for hypercholesterolemia in the American public. Dietary factors (cholesterol, saturated fatty acids, and obesity) clearly raise the cholesterol level, and they are important causes of borderline-high cholesterol. Still, the unexplained decline of LDL receptor activity with aging contributes importantly to borderline high levels and cannot be ignored. The loss of estrogen-stimulated LDL receptor synthesis after menopause is an important contributor to elevated cholesterol in postmenopausal women. In addition, several genetic defects inherited singly appear to be responsible for moderate hypercholesterolemia. Some of these defects may represent genetic hypersensitivity to diet, and dietary therapy alone may provide adequate cholesterol lowering. Other defects impart resistance to dietary control, and use of a single cholesterol-lowering drug may be required. With the exception of heterozygous FH, most cases of severe hypercholesterolemia appear to be the result of the coexistence of at least two defects in LDL metabolism, and as a rule, they can be treated successfully only by using cholesterol-lowering drugs in combination. PMID- 1931867 TI - Relation of fasting plasma insulin concentration to high density lipoprotein cholesterol and triglyceride concentrations in men. AB - Low plasma high density lipoprotein (HDL) cholesterol concentration is a risk factor for coronary heart disease (CHD) and is frequently associated with high triglyceride concentration. Both of these abnormalities have been related to insulin resistance as estimated by plasma insulin concentrations and to measures of obesity, regional adiposity, and physical fitness. To determine which of these variables (fasting plasma insulin, obesity as measured by body mass index [BMI], or regional adiposity as measured by waist to hip ratio [WHR]) best identifies men with low HDL cholesterol and high triglyceride concentrations, we divided 83 men, aged 50-65 years, who were free of CHD or diabetes, into tertiles based on BMI, WHR, or fasting plasma insulin concentration. Only for plasma insulin tertiles were there statistically significant differences in HDL cholesterol (tertile 1, mean +/- SEM, 1.34 +/- 0.08 mmol/l; 2, 1.16 +/- 0.05 mmol/l; 3, 1.10 +/- 0.06 mmol/l; p less than 0.03) and triglyceride (tertile 1, 1.05 +/- 0.08 mmol/l; 2, 1.48 +/- 0.12 mmol/l; 3, 1.82 +/- 0.17 mmol/l; p less than 0.005) concentrations. In forward stepwise regressions with HDL cholesterol and triglyceride as dependent variables, fasting insulin concentration but not BMI, WHR, or maximal oxygen uptake (VO2max), a measure of physical fitness, predicted HDL cholesterol (R2 = 0.07, p less than 0.02) and triglyceride (R2 = 0.20, p less than 0.001) concentrations. The data suggest that plasma insulin concentration is an important predictor of HDL cholesterol and triglyceride concentrations independent of BMI, WHR, or VO2max. PMID- 1931868 TI - Collagen synthesis in cultured aortic smooth muscle cells. Modulation by collagen lattice culture, transforming growth factor-beta 1, and epidermal growth factor. AB - We investigated the effects of transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF) on the protein synthesis and production of collagen in cultured smooth muscle cells (SMCs) from the aortic media of pigs. SMCs were cultured as monolayers on plastic as well as in three-dimensional collagen lattices to gain some information about the influence of a preexisting collagenous matrix on the growth factor-induced effects. A 48-hour exposure of SMCs to TGF-beta 1 at concentrations of 5 ng/ml in the presence of 1% serum caused a marked enhancement of the production of collagen and noncollagen proteins. The rate of net collagen production by SMCs exposed to TGF-beta 1 was approximately threefold higher than that of control cells. Moreover, TGF-beta 1 specifically stimulated collagen synthesis, resulting in a greater proportion of collagen in total proteins synthesized compared with controls. The preexisting matrix of collagen lattices affects the response of SMCs to TGF-beta 1 and EGF. In monolayer cultures the collagen proportion increased twofold under the influence of TGF-beta 1, whereas in collagen lattices the specific stimulation of collagen synthesis was lower. We found that EGF enhanced TGF-beta 1-induced protein production in collagen lattices but not in monolayer cultures. In addition, the protein production by SMCs was influenced differently by EGF in these culture systems. Taken together, these data show a mutual influence of growth factors and extracellular matrix components on collagen production in SMCs, thus indicating that TGF-beta 1 may be an important pathophysiological regulator of collagen metabolism in the vessel wall. PMID- 1931869 TI - Connective tissue proteinases and inhibitors in abdominal aortic aneurysms. Involvement of the vasa vasorum in the pathogenesis of aortic aneurysms. AB - Recent studies have shown that increases in proteolytic activity are associated with abdominal aortic aneurysms (AAAs). We have studied samples of the dilated aortic wall, taken during corrective surgery for AAAs, in terms of the number, type, and tissue location of connective tissue proteinases and their inhibitors. Five distinct caseinolytic serine proteinases and six gelatinolytic metalloproteinases were resolved by molecular weight by use of sodium dodecyl sulfate-substrate gel electrophoresis. Isoforms of the Mr 92,000 neutrophil gelatinase were identified by immunoprecipitation of biosynthetically labeled organ culture media. About 50% of the total radiolabeled protein secreted by AAA organ cultures was identified as the Mr 30,000 glycoprotein, tissue inhibitor of metalloproteinase (TIMP), by immunoprecipitation. Both TIMP and gelatinase were localized to the vasa vasorum by immunoperoxidase staining. However, interstitial collagenase could not be detected by any method. These results suggest the involvement of the vasa vasorum in the maintenance and possibly the genesis of AAAs. PMID- 1931870 TI - Allograft-induced arterial wall injury and response in normotensive and spontaneously hypertensive rats. AB - The role of genetically determined immune attack and blood pressure in graft rejection-induced arterial wall injury and response was assessed by studying the compliance and changes in wall structure of aortic isografts and allografts in normotensive (Wistar-Kyoto [WKY]) and hypertensive (spontaneously hypertensive [SHR]) rats. Six groups of 8-week-old rats were compared: sham-operated in both strains, isografts, and allografts between the two strains (SHR aortas grafted in WKYs, designated SWs; WKY aortas grafted in SHRs, designated WSs; isografts in SHRs, designated SSs; and isografts in WKYs, designated WWs). Each arterial graft was studied 8 weeks after transplantation for volume and compliance (pressures of 75-175 mm Hg) under basal conditions. The amounts of collagen, elastin, and nuclei in the media and intima of the walls of control and grafted aortas were quantified morphometrically. Isografts and controls had the same mechanical characteristics under basal conditions: the arterial volume and arterial compliance of hypertensive rats were lower than those of normotensive rats (p less than 0.001). Allografts had a greater initial volume (p less than 0.001) and a lower compliance (p less than 0.001) than did isografts. Allografts in SHRs (SSs) were initially dilated, whereas allografted WKYs (WWs) were not. There was intimal proliferation in hypertensive isografts (14 +/- 0.77 microns) and in both types of allografts (WS, 69 +/- 1.55 microns; SW, 44 +/- 1.81 microns); nucleus density was higher in hypertensive allografts (WS) than in normotensive allografts (SW); and collagen density was also higher in SW than in WS allografts. Allografts had decreased medial thickness and decreased smooth muscle cell density.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931871 TI - Hemin: a possible physiological mediator of low density lipoprotein oxidation and endothelial injury. AB - Oxidized low density lipoprotein (LDL), formed in vivo from presently unknown reactions, may play a role in atherogenesis. In vitro, transition metals such as iron and copper will facilitate LDL oxidation, but these metals are unlikely to exist in free form in normal body fluids. We have explored the possibility that LDL oxidation may be promoted by heme, a physiologically ubiquitous, hydrophobic, iron-containing compound. Indeed, during several-hour incubation, heme caused extensive oxidative modification of LDL; however, such modification requires only minutes in the presence of small amounts of H2O2 or preformed lipid hydroperoxides within the LDL. Oxidative interactions between heme, LDL, and peroxides lead to degradation of the heme ring and consequent release of heme iron, which further accelerates heme degradation. Coupled (evidently iron catalyzed) heme degradation and LDL oxidation are both effectively inhibited by hydrophobic antioxidants and iron chelators. That such hemin-induced LDL oxidation may be involved in atherogenesis is supported by the finding that LDL oxidized by hemin is extremely cytotoxic to cultured aortic endothelial cells. Overall, these investigations not only lend support to the idea that LDL oxidation by physiological substances such as heme may play a role in the process of atherogenesis but also may have broader implications, as similar oxidative reactions between heme and unsaturated fatty acids may occur consequent to hemorrhagic injury. PMID- 1931872 TI - Hypercholesterolemia and atherosclerosis change vascular reactivity in rabbits by different mechanisms. AB - Vasomotor reactivity was assessed in vitro in arterial segments obtained from rabbits with different stages of atherosclerosis. Rabbits were fed a standard chow diet (controls) or a cholesterol-enriched diet to induce hypercholesterolemia and atherosclerosis. A third group received the hydroxymethylglutaryl coenzyme A reductase inhibitor, lovastatin, simultaneously with the cholesterol diet. Contractile responses of thoracic aortas to norepinephrine, serotonin, and potassium-rich solution, as well as endothelium dependent dilations to acetylcholine, were compared after 2 and 4 months on the respective diet. Additionally, plasma cholesterol levels and the amount of plaques covering the intimal surface (as a percentage of the intimal surface) were determined; transmission electron microscopy of atherosclerotic arteries was also performed. After 2 months, the only difference was an enhancement of contractile responses to serotonin in the cholesterol-fed versus the control group. After 4 months on the diet, contractile responses to serotonin were further enhanced, and norepinephrine- and potassium-induced vasoconstrictions were now also significantly enhanced in cholesterol-fed animals versus controls. Endothelium-dependent vasodilations were simultaneously reduced in cholesterol fed animals. These alterations were partly prevented in cholesterol-fed and lovastatin-treated animals. Suppression of nitric oxide synthesis in control aortas by NG-nitro-L-arginine did not reveal any significant increases in contractile responses. Contractile responses to serotonin were enhanced after 2 months on the diet but before the appearance of intimal plaques, whereas attenuation of endothelium-dependent dilations, as well as the further enhancement of contractile responses to serotonin and to other agonists, were closely correlated with the degree of intimal plaques after 4 months on the diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931873 TI - Effect of corn and coconut oil-containing diets with and without cholesterol on high density lipoprotein apoprotein A-I metabolism and hepatic apoprotein A-I mRNA levels in cebus monkeys. AB - The mechanism(s) by which diets containing corn or coconut oil (31% of energy as fat) totally free of cholesterol or with 0.1% added cholesterol by weight (0.3 mg/kcal) affect plasma high density lipoprotein cholesterol (HDL-C), apoprotein (apo) A-I levels, apo A-I kinetics, and hepatic apo A-I mRNA concentrations were investigated in 26 cebus monkeys. Coconut oil-fed monkeys had elevated levels of plasma total cholesterol (217%), very low density lipoprotein plus low density lipoprotein cholesterol (331%), HDL-C (159%), and apo A-I (117%) compared with corn oil-fed animals. Although the addition of cholesterol to the corn oil diet significantly increased these parameters, no such effects were seen when cholesterol was added to the coconut-oil diet. Both the type of fat and cholesterol in the diet significantly affected HDL apo A-I metabolism by decreasing apo A-I fractional catabolic rate and increasing apo A-I production rate in the coconut oil-fed groups. The decrease in apo A-I fractional catabolic rate in the coconut oil-fed animals was also associated with an increase in the HDL core lipid to surface ratio. Liver apo A-I mRNA abundance was elevated in the coconut oil-fed groups; however, dietary cholesterol had no affect on these levels. The lack of parallel effects of dietary fat and cholesterol on apo A-I production rate and liver apo A-I mRNA levels suggests that the increase in the apo A-I production rate observed in the coconut oil-fed groups resulted from the fat-induced rise in liver apo A-I mRNA abundance, whereas the cholesterol-induced rise in the apo A-I production rate resulted from a mechanism other than changes in liver apo A-I mRNA levels. PMID- 1931874 TI - High prevalence of cardiovascular risk factors in the Seychelles (Indian Ocean). AB - In recent years, increasingly high rates of cardiovascular diseases have been recorded in the Seychelles. A survey was performed to investigate the prevalence of cardiovascular risk factors in that population, which is shifting from its traditional habits to a westernized lifestyle. The Seychelles population is of predominantly black African origin. A sex- and age-stratified random sample of 1,309 subjects was drawn from 21,256 people aged 25-64 years. A response rate of 86% was achieved. The data showed a high prevalence of hypertension (25%) and cigarette smoking (54%) in men and a high prevalence of hypertension (20%) and obesity (21%) in women. Hypercholesterolemia (greater than 6.5 mmol/l) was found in 9% of men and 15% of women. High density lipoprotein cholesterol levels (mean +/- SD) were higher in men (1.42 +/- 0.49 mmol/l) than in women (1.36 +/- 0.34 mmol/l). High levels of lipoprotein(a) (mean +/- SD) were found both in men (319 +/- 362 mg/l) and women (328 +/- 415 mg/l). The high prevalence of cardiovascular risk factors identified in the Seychelles indicates a pressing current need for effective preventive strategies. PMID- 1931875 TI - The effect of fasting triacylglyceride concentration and apolipoprotein E polymorphism on postprandial lipemia. AB - To determine if apolipoprotein (apo) E polymorphism influences postprandial lipemia and hence can help explain the wide range of lipemic responses to a standardized fat meal observed previously, blood samples were collected from 25 healthy men whose postprandial responses to a standardized fat meal had been measured. Venous blood samples had been obtained before the fat meal (0.73 g fat/kg containing vitamin A) and hourly thereafter for 8 hours, plasma and chylomicron triacylglyceride (TAG) concentrations had been determined, and retinyl esters (REs) in the chylomicron and nonchylomicron fractions had been measured. The original results were reanalyzed by apo E phenotype (six E2/3; 14 E3/3; four E3/4 and one E4/4, grouped as E4). Contrary to what is known about the epsilon 4 allele, the apo E4 group displayed a significantly greater response curve than did either the apo E2/3 or E3/3 groups for both plasma TAG and chylomicron RE concentrations (p less than 0.01), as reflected in a later chylomicron RE peak for the apo E4 group (p less than 0.05). The E4 group tended (p = 0.18) to have a 40% higher fasting TAG than did either of the other groups, which may reflect bias in the selection of subjects. As fasting TAG is an important determinant in postprandial lipemia, results were normalized for this variable. After adjustment, the E4 group had the lowest TAG response relative to the E3/3 group (p less than 0.01). Our findings suggest that controlling for apo E phenotype may help to reduce interindividual variation in the postprandial response to a standard fat meal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931876 TI - Vascular responses to platelet activation in normal and atherosclerotic primates in vivo. AB - Platelets release vasoactive substances that may contribute to augmented vasoconstriction. In this study, we examined vascular responses to activation of platelets in vivo by infusion of collagen. Purified bovine collagen was infused into the blood-perfused hind limb of normal and atherosclerotic cynomolgus monkeys. Resistance of the total limb and large arteries was measured at constant flow. In normal monkeys, collagen produced a decrease in total limb resistance, with a modest constrictor response of the large arteries. In atherosclerotic monkeys, collagen produced a transient, small decrease in total limb resistance, with pronounced constriction of large arteries. Indomethacin (5 mg/kg i.v.) and the thromboxane A2/prostaglandin H2 receptor antagonist SQ29,548 (2 mg/kg i.v.) virtually abolished the large-artery constrictor response to collagen in atherosclerotic monkeys. The 5-HT2-serotonergic receptor antagonist ketanserin (0.6 mg/kg i.v.) had no effect on the vasoconstrictor response. We conclude that 1) large arteries constrict and small vessels dilate in response to collagen mediated activation of platelets in vivo in normal and atherosclerotic monkeys, 2) large-artery constriction in response to activation of platelets is augmented in atherosclerotic monkeys, and 3) the augmented large-artery constriction in atherosclerotic monkeys may be mediated primarily by thromboxane. The findings provide evidence that platelets may contribute to augmented constrictor responses of atherosclerotic arteries. PMID- 1931877 TI - Metabolism and turnover of cell surface-associated heparan sulfate proteoglycan and chondroitin sulfate proteoglycan in normal and cholesterol-enriched macrophages. AB - Analysis of sulfur-35-labeled proteoglycans indicated that cholesterol-enriched pigeon peritoneal macrophages synthesized 42% more 35S-labeled proteoglycan when compared with control macrophages during a 24-hour incubation. Proteoglycan turnover was subsequently studied in radiolabeled macrophage cultures after a 1-, 3-, 6-, 12-, or 24-hour chase with fresh media. During the chase, intracellular proteoglycan disappeared rapidly, whereas there was a small accumulation of 35S labeled proteoglycan in the media that plateaued at about 6 hours and remained relatively constant thereafter. Pericellular heparan sulfate proteoglycan and chondroitin sulfate proteoglycan disappeared throughout the chase and did not appear to accumulate in the media or in the intracellular compartment. The rapid disappearance of intracellular proteoglycans along with the relative lack in metabolism of media proteoglycans indicated that the majority of pericellular proteoglycans were metabolized via an intracellular degradative pathway. Kinetic analysis of pericellular proteoglycans revealed the presence of a single pool of heparan sulfate proteoglycan (half-life [t1/2] = 6.9 hours) and a single pool of chondroitin sulfate proteoglycan (t1/2 = 11.5 hours) in control macrophage cultures. Cholesterol-enriched macrophage cultures also contained a single pool of pericellular heparan sulfate proteoglycan (t1/2 = 7.3 hours) but contained two pools of chondroitin sulfate proteoglycan (t1/2 = 0.8 hour and 25.9 hours). PMID- 1931878 TI - Molecular cloning, sequence, and expression of cynomolgus monkey cholesteryl ester transfer protein. Inverse correlation between hepatic cholesteryl ester transfer protein mRNA levels and plasma high density lipoprotein levels. AB - A cDNA clone containing the coding region for cynomolgus monkey cholesteryl ester transfer protein (CETP) was isolated by the polymerase chain reaction with primers based on the human CETP cDNA sequence and cDNA synthesized from liver poly (A+) RNA. Analysis of that cDNA indicated that the nucleotide and amino acid sequences of cynomolgus monkey CETP were greater than 95% homologous with the human sequences. A fragment of the cDNA was used to develop an internal standard/RNAse protection assay that allowed precise quantification of CETP mRNA levels. Analysis of total RNA from various tissues with this assay revealed that the liver and thoracic aorta expressed high levels of CETP mRNA; the mesenteric fat, adrenal gland, spleen, and abdominal aorta had low but detectable levels of the mRNA; and the brain, kidney, intestine, and skeletal muscle had undetectable levels of that mRNA. When the monkeys were made hypercholesterolemic by a high fat, high-cholesterol (HFHC) diet, hepatic levels of CETP mRNA increased from 1.6 +/- 0.4 pg/micrograms total RNA (mean +/- SEM) to 4.1 +/- 0.8 pg/micrograms (p less than 0.005); mesenteric fat CETP mRNA increased from 0.4 +/- 0.1 pg/micrograms total RNA to 5.3 +/- 2.2 pg/micrograms (p less than 0.05); and plasma CET activity increased approximately fourfold. The CETP mRNA levels in the thoracic and abdominal aortas were not significantly increased in monkeys fed the HFHC diet, even though those animals had gross atherosclerosis. The apoprotein E mRNA levels, however, were markedly increased in the aortas of monkeys with atherosclerosis, with the largest increase occurring in the abdominal aorta. Taken together, these data suggest that lipid deposition in the artery was not accompanied by increased expression of the CETP gene in that tissue. Statistical analysis showed that a strong, negative correlation existed between hepatic CETP mRNA levels and both high density lipoprotein cholesterol (r = -0.85, p less than 0.001) and apoprotein A-I (r = -0.84, p less than 0.001). These data suggest that HFHC diet-induced changes in high density lipoprotein metabolism may be linked to altered expression of a function CETP gene. PMID- 1931879 TI - Reduced proteoglycan binding of low density lipoproteins from monkeys (Macaca fascicularis) fed a fish oil versus lard diet. AB - We examined the effect of isocaloric substitution of dietary fish oil for lard on the properties of low density lipoproteins (LDL) important in binding to arterial proteoglycans (PG). Cynomolgus monkeys (n = 10) were fed atherogenic diets enriched in fish oil or lard in a crossover study consisting of two 15-week phases of atherogenic diet separated by a 6-week monkey chow "wash-out period." LDL were isolated from plasma during each dietary phase, characterized for chemical and physical properties, and assessed for their ability to interact in vitro with arterial PG. Plasma LDL cholesterol was similar during fish oil and lard consumption (356 +/- 34 and 331 +/- 17 mg/dl, mean +/- SEM), but during fish oil feeding relative to that of lard, LDL size was smaller (4.2 +/- 0.1 versus 4.9 +/- 0.1 g/mumol) and LDL particles differed in chemical composition. When animals were fed fish oil, significantly fewer (p less than 0.05) LDL particles bound to PG in both dietary phases: 1.00 +/- 0.27 (x10(12)) versus 5.31 +/- 0.83 (x10(12)) particles/micrograms PG in phase 1 and 3.56 +/- 0.67 (x10(12)) versus 6.00 +/- 0.52 (x10(12)) in phase 2 for LDL from animals fed fish oil and lard, respectively. These studies indicate that dietary fat-induced changes in LDL particles lead to altered in vitro interactions with artery wall PG and suggest a novel mechanism for the protective effect of fish oil against atherosclerosis. PMID- 1931880 TI - Relation of extent of extracranial carotid artery atherosclerosis as measured by B-mode ultrasound to the extent of coronary atherosclerosis. AB - The extent of carotid artery atherosclerosis as measured by B-mode ultrasound has been shown to be strongly and independently correlated with the presence or absence of coronary atherosclerotic disease (CAD), but no studies to date have used carotid B-mode ultrasound to compare the extent of atherosclerotic disease in the two arterial circulations. We used data from a registry of patients undergoing cardiac catheterization and B-mode ultrasound of the carotid arteries to compare the extent of CAD (number of major coronary vessels with 50% or greater stenosis as judged by a consensus interpretation) with the extent of extracranial carotid atherosclerosis. Four hundred thirty-four patients (234 men, 200 women) greater than 40 years of age were stratified by gender and then divided into quartiles on the basis of a B-mode score that was derived by summing arterial wall thickness at nine sites in the left and nine sites in the right carotid arteries. Evaluation of extent of CAD for the four B-mode quartiles showed that men in the lowest B-mode quartile were over six times more likely to have normal coronary arteries than three- to four-vessel CAD, while men in the highest B-mode quartile were over 10 times more likely to have three- to four vessel CAD than normal coronary arteries. The findings were similar for women but not as dramatic. Gender-specific discriminant function models using traditional risk factors alone or in combination with B-mode score were developed to predict the extent of CAD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931881 TI - Lipid accumulation in rabbit aortic intima 2 hours after bolus infusion of low density lipoprotein. A deep-etch and immunolocalization study of ultrarapidly frozen tissue. AB - The intima from aortas of normal New Zealand White rabbits was studied 2 hours after infusion of 320 mg human low density lipoprotein (LDL), resulting in a plasma concentration of at least five times and maximally 20 times the values found in normal rabbit serum. The following techniques were used: 1) ultrarapid freezing without chemical fixation, followed by freeze-etching; 2) immunofluorescence microscopy; and 3) postembedding immunogold-labeling electron microscopy. In the latter two methods MB47, a murine monoclonal antibody against human apolipoprotein B, was used as the primary antibody. Control rabbits were infused with the same volume of buffer only. Rotary-shadowed replicas of samples from the LDL-injected rabbits showed the deposition of lipidlike particles in the subendothelial-intimal space that were the size of the injected LDL (23 nm). In focal areas of the intima, groups of 23-nm-sized lipidlike particles and larger lipidlike structures were found enmeshed in the extracellular matrix. Control replicas were essentially free of lipid deposition. Immunofluorescence microscopy of frozen aortic cross sections showed an overall increase in apolipoprotein B in the intima of the LDL-injected rabbits. The presence of apolipoprotein B in the intima was also confirmed by immunoelectron microscopy. These in vivo results show that clustering of LDL-sized particles occurs in the intima within 2 hours of excessive LDL uptake. It also demonstrates the interaction of these LDL-sized particles with the filaments of the extracellular matrix. The clustering of the LDL-sized particles supports the possibility that LDL self-aggregation may occur in vivo and that components of the extracellular matrix are involved in this process. PMID- 1931882 TI - Enhanced hepatic uptake and processing of cholesterol esters from low density lipoprotein by specific lactosaminated Fab fragments. AB - Reduction of the blood levels of low density lipoprotein (LDL) is important for lowering the incidence of atherosclerosis. In this study, LDL was directed to rat parenchymal liver cells by lactosaminated Fab fragments of anti-apolipoprotein B antibodies (LacFab). We followed the fate of intravenously injected complexes of LacFab and [3H]cholesteryl oleate-labeled LDL. Complexing of LacFab to LDL led to rapid disappearance of LDL from the circulation. At 30 minutes after injection, the liver contained 58.5 +/- 9.0% of the injected dose (at that time the liver contained only 5.7 +/- 2.2% of an injected dose of free LDL). Liver uptake was blocked by N-acetylgalactosamine but not by N-acetylglucosamine, which indicates that galactose-specific recognition sites are responsible for the LacFab-induced hepatic uptake. By isolating liver cells, it was found that parenchymal, endothelial, and Kupffer cells account for 87%, 3%, and 10% of the total hepatic uptake, respectively. Subcellular fractionation of the liver indicated that the complexes are rapidly internalized and transported to lysosomes. Within 1 hour after injection, virtually all the [3H]cholesteryl oleate of the internalized LDL was hydrolyzed; hydrolysis was followed by excretion of radioactivity into the bile. Compared with rats injected with native [3H]cholesteryl oleate-labeled LDL, eight times as much radioactivity was excreted into the bile during the first 4 hours after the injection of LacFab-complexed [3H]cholesteryl oleate-labeled LDL. Thus, LacFab induces enhanced hepatic uptake of LDL via galactose receptors on the parenchymal cells, followed by processing in lysosomes and excretion into the bile. In this way, LacFab induces an increased irreversible removal of LDL cholesterol from the body. PMID- 1931883 TI - Dynamics of shear-induced redistribution of F-actin in endothelial cells in vivo. AB - The steady-state responses of endothelial cell F-actin distribution to changes in in vivo shear stress have been well documented. The purpose of the current work was to define the dynamics of redistribution of F-actin in the period immediately after experimental changes in shear. We used abdominal aortic coarctation in rabbits to experimentally increase shear stress downstream from the coarctation by approximately twofold. In situ staining was employed to track subsequent F actin redistribution. Within 12-15 hours, the number of stress fibers in the central regions of the cells decreased, and some separation of junctional actin in adjacent cells occurred. Long, central stress fibers of variable thickness were evident at 24 hours, but the band of actin normally seen at the periphery of the cells could no longer be distinguished. The redistribution of F-actin was completed over the next 24 hours by an increase in thickness of central stress fibers. Restoration of normal F-actin distribution after coarctations were removed proceeded more slowly. The long, thick stress fibers that were induced by high shear were replaced by thinner or shorter microfilament bundles 48 hours after the coarctations were removed. At 72 hours, central stress fibers were primarily long, thin structures. Peripheral F-actin was not fully restored at this time. Peripheral F-actin was restored at 1 week after removal of the coarctation, but there were still more and longer stress fibers at this time than were observed in control aortas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931884 TI - Stimulating effect of oxidized low density lipoproteins on plasminogen activator inhibitor-1 synthesis by endothelial cells. AB - Oxidized low density lipoproteins (ox-LDL) are thought to accelerate atherogenesis. It was recently demonstrated that patients with coronary heart disease have defects in plasma fibrinolysis due to increased plasminogen activator inhibitor-1 (PAI-1) levels. Investigation of PAI-1 synthesis by endothelial cells may allow insight into the effect of native LDL (N-LDL) and ox LDL on endothelial cells. In the present study, secretion of PAI-1 by human umbilical vein endothelial cells (HUVEC) in culture was evaluated after incubation with N-LDL and ox-LDL. Ox-LDL were obtained by peroxidation under ultraviolet radiation, which induced compositional changes in LDL, namely, a decrease in the levels of arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and alpha-tocopherol and an increase in the malondialdehyde content. Ox-LDL induced a dose-dependent increase in PAI-1 secretion by HUVEC as assayed by an enzyme-linked immunosorbent assay. After a 24-hour incubation, a twofold increase in the PAI-1 content was observed with 50 micrograms/ml ox-LDL protein. Studies with inhibitors of protein synthesis and metabolic labeling with [35S]methionine confirmed that PAI-1 synthesis was stimulated by ox-LDL. N-LDL had no detectable effect on PAI-1 secretion. Binding studies with radiolabeled lipoproteins showed that the effect of ox-LDL was independent of the B/E receptor. Our experiments indicate that ox-LDL stimulate PAI-1 secretion from HUVEC and that this effect may involve a scavenger receptor. PMID- 1931885 TI - Comparison of CI-976, an ACAT inhibitor, and selected lipid-lowering agents for antiatherosclerotic activity in iliac-femoral and thoracic aortic lesions. A biochemical, morphological, and morphometric evaluation. AB - Due to the potential importance of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) in the generation of lipid-filled monocytes-macrophages, the ACAT inhibitor CI-976 (2,2-dimethyl-N-(2,4,6-trimethoxyphenyl)dodecanamide) was evaluated relative to selected lipid-lowering agents for their effect on atherosclerotic lesion regression and progression. Atherosclerotic lesions comparable in composition to human fatty streaks were induced by chronic endothelial denudation in the iliac-femoral artery of hypercholesterolemic New Zealand White rabbits before intervention, while naturally occurring fatty streaks developed in the thoracic aorta. CI-976 administered in a hypercholesterolemic diet at a dose that did not lower plasma cholesterol prevented the accumulation of monocytes-macrophages within the preestablished iliac-femoral lesion and reduced the foam cell area by 27-29% relative to the initiation of intervention. CI-976 also blunted the development of thoracic aortic fatty streak-like lesions and decreased the cholesteryl ester enrichment by 46%. CI-976 had no effect on plasma triglycerides and, more importantly, had no effect or decreased liver, iliac-femoral, and thoracic aortic free cholesterol content. Dietary intervention alone increased monocyte-macrophage involvement in the iliac-femoral lesion despite reductions in plasma, liver, and thoracic aortic cholesterol content. Conventional lipid-lowering therapy such as cholestyramine or cholestyramine/niacin required substantial decreases in plasma cholesterol levels to achieve comparable vascular changes. We conclude that inhibition of ACAT within the arterial wall by the potent and specific ACAT inhibitor CI-976, even in the absence of plasma cholesterol lowering, can result in the inhibition of atherosclerotic lesion progression and can enhance regression. PMID- 1931886 TI - Shear stress regulates smooth muscle proliferation and neointimal thickening in porous polytetrafluoroethylene grafts. AB - High shear stress appears to decrease wall thickening in diseased arteries and vascular grafts. To determine if increased shear stress diminishes smooth muscle (SMC) proliferation, we studied the effect of increased blood flow on neointimal thickening in porous polytetrafluoroethylene grafts implanted in baboons. An aorto-aortic 5-mm graft was placed in tandem with a pair of aorto-iliac 5-mm grafts, so that the proximal graft supplied all flow to both distal grafts. At 12 weeks, calculated luminal shear stress in proximal grafts was twice that in distal grafts (24 +/- 8 versus 11 +/- 5 dynes/cm2; p less than 0.05). All grafts were completely endothelialized. The neointimal cross-sectional area in proximal grafts was about half as large as in distal grafts (3.36 +/- 1.61 versus 5.93 +/- 0.61 mm2; p less than 0.05). Proximal grafts also had significantly less SMC proliferation (0.14 +/- 0.05% versus 0.24 +/- 0.10%; p less than 0.05) and SMC volume (6.1 +/- 4.0 versus 12.4 +/- 2.6 mm3/cm graft; p less than 0.01) when compared with distal grafts. We conclude that the elevation in shear stress in the proximal graft, which remained within the physiological range, inhibits SMC proliferation and neointimal thickening in these grafts. PMID- 1931887 TI - Analysis of an emergency dental service provided at a children's hospital. AB - An analysis was undertaken of the evening, weekend and public-holiday emergency dental service provided at the Royal Belfast Hospital for Sick Children during one calender year (1987). Dental emergencies accounted for 4% of all attendances during these periods at the Accident & Emergency Department. Toothache, with or without abscess, was the most frequent dental complaint (49%) and abscesses were most frequently associated with primary first molars. Acute trauma was the second most frequent dental complaint (39%) and traumatic injuries were most commonly caused by falls and bicycle accidents. Tooth displacement was was the most common dental injury of primary and permanent teeth. Complaints other than toothache, abscess or traumatic injury accounted for only 12% of dental emergencies. PMID- 1931888 TI - The effect of the position and orientation of unerupted premaxillary supernumerary teeth on eruption and displacement of permanent incisors. AB - The hospital records of 101 consecutive patients admitted for removal of premaxillary supernumerary teeth were examined. From the clinical notes and preoperative anterior occlusal radiographs the following information was noted: the position and orientation of the supernumerary teeth, and whether they caused delayed eruption, rotation or displacement of the associated permanent incisors. There were 140 supernumerary teeth (mean per child = 1.39). Delayed eruption of permanent incisors occurred in 56% of cases. Supernumerary teeth situated between central incisors caused eruption delay infrequently, but were associated with rotation and displacement of permanent incisors more frequently than those that overlapped the incisors on the radiographs. Supernumerary teeth that were orientated vertically caused eruption delay more frequently than those that were inverted, but the orientation of supernumerary teeth did not influence rotation or horizontal displacement of the permanent incisors. PMID- 1931889 TI - Complete eruption of a malformed mandibular permanent molar following extraction of a complex odontome. AB - A case is described in which a complex odontome, associated with an unerupted and displaced mandibular permanent molar, presented as an acute infection of an edentulous area. Surgical removal of the odontome led to the spontaneous eruption of the tooth. PMID- 1931890 TI - Pycnodysostosis associated with delayed and ectopic eruption of permanent teeth. AB - The oral and facial manifestations of pycnodysostosis (Maroteaux-Lamy syndrome) are reviewed, and illustrated by a case in which the presenting feature was delayed and ectopic eruption of permanent teeth. PMID- 1931891 TI - A clinical study of a microfilled composite resin for labial veneers. AB - Two-hundred and eighty-nine composite resin-full labial veneers were placed after labial enamel reduction in children and adolescents and reviewed after periods of up to 3 years. The median (+/- S.E.) survival time was 35.6 +/- 0.8 months with 42 (14%) of the veneers considered to have failed. There was a small incidence of marginal staining, no deterioration in gingival health, and patient satisfaction was high. PMID- 1931892 TI - [Mammary pathology--permanent challenge for clinical pathology]. PMID- 1931893 TI - [Mammary pathology]. PMID- 1931894 TI - [Mastopathy. Histological forms and long-term observations]. AB - Long-time observation of women with bioptically secured mastopathy has provided evidence to the effect that, in the context of statistical mean values, aggravated carcinoma risk needed to be expected only along with the presence of atypical epithelial proliferation. The risk to women with atypical Grade III mastopathy (atypical ductal and lobular hyperplasia) was found to be at least four times as high as that to women with simple Grade I mastopathy or to patients without any previous mastopathy record. Grade III mastopathy is identical with atypical hyperplasia of mammary gland parenchyma (according to nomenclature recommendations by the Consensus Meeting of the American Cancer Society, 1985). No hard evidence has, as yet, been produced as to whether atypical hyperplasia is a precancerous lesion or simply a marker for breast cancer. Women thus affected anyway should be kept under long-time monitoring as a high-risk group. PMID- 1931895 TI - Flow cytometry of breast cancer. AB - Flow cytometry (FCM) has become a generally accepted analytical method of worldwide application. Considerably achievements in flow cytometry hardware, staining techniques, especially immunoflow cytometry, together with progress in software programmes have significantly contributed to persistent expansion of the method. Some of the inbuilt rapidity of FCM has been lost because of additional preparatory steps and incubations. Mammary carcinoma is one of those malignant tumours which have been most extensively investigated by FCM. Evidence has been repeatedly produced to the existence of correlations among the most important FCM data, prognostic factors, and follow-up findings. Further improvement of the method and search for the best possible clinical application actually are the main challenges to FCM of breast cancer, today. PMID- 1931896 TI - Immunohistochemical analysis of estrogen and progesterone receptors in benign breast diseases. AB - Surgical specimens of 62 patients with fibrocystic disease, 39 with fibroadenoma and 11 with intraductal papilloma were evaluated with ER-ICA and PgR-ICA methods. Positive nuclear staining was only observed in the epithelial components. The myoepithelium, myofibroblasts, fibroblasts and the so called apocrine epithelium, however, did not contain steroid receptors. Some steroid receptor negative cases occurred among the atrophic and non-proliferating fibrocystic diseases. In the proliferating benign alterations, particularly in those considered preneoplastic, e.g. radial scar, ductal and lobular atypical epithelioses, such as carcinoma lobulare in situ and florid intraductal papilloma there was a positive staining for estrogen receptor and progesterone receptor in the epithelial cells. Authors' results seem to serve as a theoretical basis for the hormonal influence of precarcinomatous cases and to explain the success of antisteroid therapy in patients with fibrocystic disease. PMID- 1931897 TI - Malignant lymphomas of the breast. AB - Primary non-Hodgkin malignant lymphomas (ml) of the breast are infrequent (0.05 0.5% of all malignant breast tumours). In the present series, 10 cases seen between 1980-1989 from the files of the Malignant Lymphoma Reference Center, Pecs, Hungary, were re-evaluated. Nine out of the 10 cases were of B-cell origin, 4/10 of low grade and 6/10 of high grade malignancy. In the latter group there were 4 centroblastic ml-s. In one of them transformation of a low grade MALT-type ml to centroblastic ml was suspected. Another high grade B-cell ml was similar to the recently described mediastinal clear cell ml, B-cell type. At presentation, 7 out of 10 patients were in clinical stage IE. In the same period (1980-1989), 5 further cases with clinical suspicion of breast tumor had reactive lesions (florid follicular hyperplasia). PMID- 1931898 TI - [Intraductal sclerosing papilloma of the breast]. AB - Reported in this paper is a case of a woman, 21 years of age, with intraductal mammary papillomas of unusual sclerogenicity, accompanied by fibrocystic disease of the breast. PMID- 1931899 TI - The effects of fasting on plasma corticosterone kinetics in rats. AB - Plasma corticosterone clearance in anaesthetized rats was measured from the disappearance of radioactivity after a bolus injection of [3H]corticosterone. Mean fractional clearance rates were significantly (P less than 0.05) reduced after a 48 h fast, by 32 and 22% for males and females respectively. Plasma corticosterone concentrations were increased by fasting in both sexes. Corticosterone secretion rates, calculated as the product of fractional clearance and plasma corticosterone concentration, did not differ between fed and fasted groups in either sex. The mean activity (U/liver) of the rate-limiting enzyme for corticosterone degradation, hepatic 4,5-dihydrocorticosterone:NADP+ delta 4 oxidoreductase, was significantly reduced by 51 and 78% after fasting in males and females respectively. This was due to changes in both the soluble and microsomal forms of the enzyme. The binding capacity of corticosterone-binding globulin in plasma was significantly reduced by fasting in females (P less than 0.001), but was not altered in males. The results suggest that reduced hormone clearance is the dominant cause of fasting hypercorticosteronaemia in the rat. PMID- 1931901 TI - The effect of concentration of tannin-rich bean hulls (Vicia faba L.) on activities of lipase (EC 3.1.1.3) and alpha-amylase (EC 3.2.1.1) in digesta and pancreas and on the digestion of lipid and starch by young chicks. AB - The effect of different concentrations of tannin-rich field-bean (Vicia faba L.) hulls at 0, 20, 50, 150 and 300 g/kg dietary inclusion on the activities of lipase (EC 3.1.1.3) and alpha-amylase (EC 3.2.1.1) in digesta and pancreas and on the digestion of lipid and starch was studied in 2-3-week-old male broiler chicks. Low dietary concentrations of tannins (20 and 50 g hulls/kg) enhanced the activity of lipase in digesta from both the jejunum and ileum, the 20 g hulls/kg effecting the greatest enhancement, but no stimulatory effect on the activity of digesta alpha-amylase was observed. High dietary concentrations of tannins (150 and 300 g hulls/kg) inhibited both lipase and alpha-amylase activities in digesta from both the jejunum and ileum, the 30 g hulls/kg causing the most inhibition. Tannins did not increase the activities of lipase or alpha-amylase in pancreatic homogenates, but at high concentrations (150 and 300 g hulls/kg) they lowered slightly the pancreatic activity of alpha-amylase. Nutrient digestion was less influenced by the concentration of tannins than digesta enzyme activities. PMID- 1931900 TI - Short-term effect of whole milk and milk fermented by Pseudomonas fluorescens on plasma lipids in adult boars. AB - The short-term effects of whole milk and milk fermented by Pseudomonas fluorescens, of the amino acid composition of the diet and of feeding frequency on the level of plasma lipids, were investigated in six 1-year-old adult boars. The experimental diets contained equal amounts of protein, carbohydrates, fat and cholesterol. After an adaptation period of 5 d for each experimental treatment, blood was collected at regular intervals during 48 h and plasma levels of cholesterol, triacylglycerol, high-density-lipoprotein (HDL)-cholesterol and low density-lipoprotein (LDL)-cholesterol were examined. All variables except HDL cholesterol showed distinct diurnal fluctuations, which were substantially influenced by feeding frequency. Variations in the amino acid composition of the experimental diets, which were within a physiological range, had no effect on the level of plasma lipids. Plasma lipid levels were significantly lower when the animals received the diets containing milk instead of the diet without milk: cholesterol, triacylglycerol, and LDL-cholesterol were reduced by 5.6, 5.8 and 10% respectively (pondered means) while HDL-cholesterol remained unaffected. Fermentation of whole milk by P. fluorescens reduced the lipid-lowering effect. Our findings suggest that the intake of diets containing milk results in a lower plasma cholesterol and LDL-cholesterol level than the intake of diets with a similar nutrient content which do not contain milk. PMID- 1931902 TI - Reduction of the intake of food and water is responsible for reduction of litter growth when dams are treated with a progesterone antagonist. AB - Treatment of lactating rats with the anti-progestin Mifepristone or Onapristone adversely affects growth of their litters. The present studies aimed to elucidate the underlying mechanism. The treatment did not interfere with the behavioural interactions between mothers and pups, which are required for normal litter growth. Treatment with the antagonists had a stimulatory action on ovarian oestrogen production. However, ovarian hormones did not play a role in litter growth impairment, as this also occurred with lactating ovariectomized rats. Treatment with anti-progestins did not affect the concentrations of the macronutrients in milk (protein, lactose and lipid), nor did it change the fatty acid composition of lipid. Reduced litter growth was not related to a possible direct effect of exposure of the suckling young to the drugs via the milk. Direct injections into them unequivocally affected adrenal gland and testicular development, but did not affect their body-weight development. Milk secretion, as measured by the milk weight accumulating during 6 or 24 h following sudden removal of litters in advanced lactation, was not impaired by the treatments. However, the ingestion of food and water by dams treated with Mifepristone was significantly below that of control animals. It is concluded that litter growth impairment during treatment of lactating rats with anti-progestin results from the reduction of the intake of food and water by the mother. PMID- 1931903 TI - A computerized diet questionnaire for use in diet health education. 1. Development and validation. AB - A diet questionnaire was developed in association with a computer program to provide rapid nutritional feedback to the general public. The questionnaire was validated against 16 d of weighted diet records and biochemical variables in blood and urine. The highest Pearson correlation coefficients obtained between the questionnaire and the weighed records were for alcohol, fibre, iron, riboflavin (r 0.74, 0.67, 0.66, 0.66 respectively). Striking sex differences were shown in the results; the trend for higher correlations persisted in females. At least 65% of subjects were classified by questionnaire to within one quintile of the classification by weighed record for the majority of nutrients. PMID- 1931904 TI - Measurement and prediction of digestible energy values in feedstuffs for the herbivorous fish tilapia (Oreochromis niloticus Linn.). AB - Digestible energy (DE) values were measured in a selection of feedstuffs for the tilapia (Oreochromis niloticus Linn.) and used to develop equations for predicting DE values of a wider range of feedstuffs from chemical analyses. Preliminary work examined the influences of substitution level in a reference diet and adaptation over time on DE values for soya-bean meal. Length of adaptation period significantly affected DE values (P less than 0.01), but substitution level, over the range 200-600 g soya-bean meal/kg reference diet, did not. The DE values of sixteen feedstuffs, thirteen derived from plant sources and three animal by-products, were subsequently determined. DE values for plant derived feedstuffs were found to be higher than those quoted in the literature for trout (Oncorhynchus mykiss) and catfish (Ictalurus punctatus), whereas DE values for animal-derived feedstuffs were lower than those for trout and pigs. It was concluded that energy values quoted in tables of feed composition for other species are inaccurate when used as proxy values for tilapia. Regression equations were therefore computed using data from the present study to provide a rapid means of predicting DE values of feedstuffs for tilapia. Equations using neutral-detergent fibre as an independent variable were found to predict DE values of plant-derived feedstuffs reliably. Where fibre values were not used as independent variables, available carbohydrate and crude protein (nitrogen x 6.25) were found to be useful predictors of DE values. These equations offer the possibility of reducing the need for time-consuming digestibility trials with tilapia when formulating least-cost production diets for this species. PMID- 1931905 TI - Transport of feed selenium to different tissues of bulls. AB - The effects of different types of Se supplementation on the selenium concentration of beef, bovine internal organs and some other tissues were studied. The animals (thirty-two bulls) were kept in four dietary groups from birth until to the age of 13-14 months, and fed on rations containing either 0.03 mg Se/kg (basic level in local feeds), 0.25 mg inorganic Se supplemented as sodium selenite, or 0.25 or 0.4 mg/kg plant Se in dry matter from feed produced by spraying with sodium selenite. Samples of four muscles and ten other tissues and organs were taken at slaughter. Se was determined by an electrothermal atomic absorption method. Se supplementation significantly increased the Se concentration of all tissue samples. The maximum response was caused by the diet containing 0.40 mg/kg plant Se. In muscles, this diet raised the Se concentration by a factor of 10-12. In other samples, the increment was 1.5-7.5 fold, depending on the type of tissue. In general, plant Se raised the Se level more effectively than inorganic Se. Se supplementation did not affect the vitamin E status of muscle tissue. PMID- 1931906 TI - Intrinsic labelling of different foods with stable isotope of zinc (67Zn) for use in bioavailability studies. AB - Intrinsically-labelled foods are required to validate extrinsic-labelling techniques used to study the bioavailability of trace elements. Wheat (Triticum aestivum), peas (Pisum sativum), goat's milk, human milk, eggs and chicken meat were selected for intrinsic-labelling studies with 67Zn. Peas were grown hydroponically in enriched nutrient solution and wheat was grown in sand and watered with enriched nutrient solution. Some of the wheat plants were also given stem injections of 67Zn solution. Eggs and chicken meat were prepared by administering 67Zn intravenously to chickens, and human milk was collected after an oral dose of 67Zn in a cola drink. All the foods investigated were sufficiently enriched with 67Zn for Zn absorption studies except wheat prepared by the sand and water-culture method. PMID- 1931907 TI - Apparent zinc absorption by rats from foods labelled intrinsically and extrinsically with 67Zn. AB - A variety of foods (peas (Pisum sativum), chicken meat, eggs, goat's milk, human milk) enriched with the stable isotope 67Zn were prepared by means of intrinsic- and extrinsic-labelling procedures. They were fed to rats and apparent absorption of 67Zn determined from faecal excretion measurements using thermal ionization mass spectrometry. There were significant differences in the absorption of the extrinsic and intrinsic label which differed in magnitude between the foods tested. The extrinsic 67Zn was less well absorbed in peas, chicken meat, eggs, and human milk than intrinsic 67Zn, but in goat's milk the extrinsic 67Zn was better absorbed than the intrinsic label. These results demonstrate that extrinsically-added stable Zn isotopes do not fully exchange with endogenous Zn in many foods, and illustrate the need for caution when using extrinsic labels for Zn bioavailability studies. PMID- 1931909 TI - Nutritional implications of D-xylose in pigs. AB - Hemicellulose consists primarily of pentose sugars, joined together in a polysaccharide chain with D-xylose as the most abundant component. Ileal digestibility and urinary excretion of D-xylose and associated effects of this pentose sugar on ileal and faecal digestibility of dry matter (DM), organic matter (OM), gross energy (GE) and nitrogen were studied in pigs. Castrated pigs were prepared with a post-valvular T-caecum cannula to measure ileal digestibility. Faecal digestibility was measured in non-cannulated pigs. D-Xylose was given at dietary inclusion levels of 100 and 200 g/kg, and the control sugar, D-glucose, at a rate of 200 g/kg diet. Ileal digestibility of D-xylose as well as that of D-glucose was found to be close to 100%. The presence of D-xylose in the diet decreased ileal digesta pH and increased ileal flow of volatile fatty acids, suggesting the occurrence of microbial degradation of D-xylose in the pig small intestine. In pigs fed on the 100 g D-xylose/kg diet, 44.5% of the D-xylose intake appeared in the urine. This percentage increased significantly to 52.6 when pigs were fed on the 200 g D-xylose/kg diet. Ileal and faecal digestibility of DM, OM, GE and N, as well as N retention, decreased significantly in pigs fed on the 200 g D-xylose/kg diet. PMID- 1931908 TI - Effect of dietary lactose on salt-mediated changes in mineral metabolism and bone composition in the rat. AB - The effects of salt (sodium chloride) supplementation of rat diets (80 g/kg diet), with or without lactose (150 g/kg), were studied in weanling rats over 14 d. Dietary salt increased water intake and reduced weight gain and food conversion efficiency, but these variables were unaffected by lactose. Salt supplemented rats exhibited a three- to fivefold increase in urinary calcium excretion and a small increase in urinary magnesium and phosphorus excretion, irrespective of dietary lactose content. In addition, salt supplementation reduced plasma alkaline phosphatase (EC 3.1.3.1) activity. Lactose increased urinary Ca and Mg excretion and plasma Ca and P concentrations. Salt reduced tibia mass but not tibia mass expressed relative to body-weight, but neither variable was affected by lactose. Both tibia Mg content and concentration were reduced by salt but unaffected by lactose, and neither tibia P content nor concentration was affected by salt or lactose. Tibia Ca content was reduced by salt but this was prevented by lactose. Tibia Ca concentration was unaffected by salt or lactose, although there was a reduction (not significant) in tibia Ca concentration in animals fed on the lactose-free diet. These results show that lactose had no independent effect on bone and that reduced accretion of bone mass and mineral content in rats fed on the high-salt diets was due, at least in part, to reduced growth. Failure to offset sodium-induced hypercalciuria by a compensatory increase in net Ca absorption may have contributed to reduced bone Ca accretion. The protective effect of lactose against reduced bone Ca accretion may be due to increased Ca absorption. PMID- 1931911 TI - A potential weak allelic difference in male-specific antigen between two inbred strains of mice. AB - Differences were detected between male-specific antigen(s) from BALB/c and C57BL/10 mice. Reciprocal crosses between these strains were analysed by means of a popliteal lymph node assay enumerating cells secreting IgM and IgG in a T dependent bystander B-cell response. The responses, while being indirect, weak and variable, suggested that there are differences in 'immunogenicity' coded by Y linked (male-specific) genes. This conclusion was strengthened by the results of experiments carried out in Y-backcross mice, where spleen cells from male C57BL mice with a BALB/c-Y (B10.C-YC) stimulated low popliteal lymph node responses in female littermates in comparison with C57BL mice with their own Y-chromosome. In contradistinction, male spleen cells from a BALB/c with a C57B1/10-Y chromosome (C.B10-YB), injected into a hind footpad of a female littermate, induced a relatively higher popliteal lymph node response. PMID- 1931910 TI - Does the glycogen synthase (EC 2.4.1.21) of brown adipose tissue play a regulatory role in glucose homeostasis? AB - Glycogen synthase (GS) activity was characterized in rat brown adipose tissue (BAT) and the activity was found to be much higher than that in white adipose tissue. Prolonged starvation had no effect on the active form of GS, as found in the liver and muscle. The GS activity was similar in BAT of rats housed in an animal room (21 +/- 1 degree) whether they were fed on high-carbohydrate, high fat, or stock diets. Acclimatization of rats to cold (4 +/- 1 degree) for 2 weeks significantly increased GS activity. This increase in the cold was fivefold greater when rats were fed on high-carbohydrate diets than in control rats at room temperature fed on an identical diet. The increase was accompanied by a large accumulation of glycogen in BAT. It was concluded that GS may play an important role in BAT and may contribute to the control of blood glucose in a cold environment. Its relevance to thermogenesis requires further elucidation. PMID- 1931912 TI - Application of polymerase chain reaction (PCR) to HLA-C locus typing. AB - Polymerase chain reaction/oligonucleotide typing was used to identify HLA-Cw*0601 (Cw6) in patients with psoriasis and psoriatic arthritis. The assignment of HLA Cw*0601 was established by the concordant presence of codons for alanine (position 73), lysine (position 80) and tryptophan (position 97). The frequencies of all three codons were increased in the patient groups. PMID- 1931913 TI - Combined use of RFLP and PCR-ASO typing for HLA-DR-Dw and DQw typing. PMID- 1931914 TI - Mechanism of melatonin action. AB - Melatonin transduces the effect of photoperiod on the neuroendocrine system. Synthesis of melatonin in the pineal gland is well described, but the location of its target(s) and the mechanism of its action are little known. In attempt to localize melatonin target(s), the presence of high affinity binding sites in rat brain was determined. Such sites were detected in discrete brain areas, including the hypothalamus and anterior pituitary. Subcellular analysis indicated these binding sites were on plasma membranes, which suggests that melatonin modulates cell functions through intracellular second messengers. The effects of melatonin on second messengers were studied using the neonatal anterior pituitary, in which melatonin is known to inhibit the LHRH-induced release of LH. Studies on the effects of melatonin on second messenger indicated [corrected] that melatonin inhibits accumulation of cAMP and cGMP as well as synthesis of diacylglycerol and release of arachidonic acid. Time-course analysis indicates that inhibition by melatonin of the LHRH-induced release of LH increases following long preincubation. Since the effect of melatonin on LHRH-induced release of LH is prevented by dibutyryl cAMP, we conclude that melatonin might act by inhibiting production of cAMP. PMID- 1931915 TI - Prenatal development of the heart and the blood circulatory system. PMID- 1931916 TI - Heterogeneity of the myocardium. Function of the left and right ventricle under normal and pathological conditions. AB - A number of important differences can be found between the left ventricle (LV) and right ventricle (RV) of the heart under physiological conditions. In anatomy, the most important is probably the architecture of the atrioventricular valve and its annulus. The LV has a mitral valve (with two cusps) and a firm annulus, while the RV has a tricuspid valve with a greater total area, but relatively small cuspid areas, and an elastic annulus. The difference in the blood supply is important. Owing to high intramural pressure, the coronary flow in the wall of the LV occurs only during the diastole; in the RV it is limited only in the presence of a significant increase in intracavitary pressure. The LV myocardium is functionally "accustomed" to short-term marked changes in the systolic load (in extreme static exercise the arterial pressure rises for a short time to three times the normal value), while the RV is adapted to changes in the diastolic load (marked filling changes associated with deep breathing, for instance). The difference in the response to a long-term volume load is difficult to evaluate: between a defect of the interatrial septum and aortic insufficiency there are too many differences. A long-term pressure load seems to be tolerated better by the right ventricle: patients with severe pulmonary stenosis and a pressure six times higher than the physiological value have lived 25 years and patients with isolated corrected L-transposition of the great arteries can reach 35 years without any signs of impaired RV function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931917 TI - Effect of ischaemia on protein synthesis in neuron and glia-enriched fractions from the rabbit spinal cord. AB - The incorporation of 14C-leucine into the post-mitochondrial supernatant and neuron, glia and myelin-enriched fractions isolated from the rabbit spinal cord was studied after ischaemia and subsequent recirculation. In the cell-free system, incorporation decreased to 55% of the control value after 40 min ischaemia, but proteosynthesis returned to the pre-ischaemic value after 3 h recirculation and remained at this level during further recirculation. The incorporation of amino acids into proteins of neurons and neuroglia differed from the cell-free system and from each other. In the enriched neuronal fraction, protein synthesis fall after ischaemia and also during the first hours of recirculation, but during further recirculation it rose to 60% above the control value. In the enriched glial fraction, specific radioactivity of proteins rose abruptly immediately after ischaemia and by the fourth day there was sixfold increase as compared with control values. The results indicate that the ischaemia induced decrease in protein synthesis is only transient and that a significant increase occurs in the surviving cell populations, especially the neuroglia. The functional changes caused by spinal cord ischaemia are irreversible, however. PMID- 1931918 TI - Effect of prostaglandin F2 alpha on the contractile tissues of the respiratory system of the cat in experimental airway inflammation. AB - The in vitro reactivity of the smooth musculature of the trachea and lungs to PGF2 alpha, was studied in control cats and cats with experimental airway inflammation induced by turpentine oil. No changes were found in the reactivity of the tracheal smooth muscle, but the reactivity of the pulmonary tissue was significantly raised compared with the controls. The results indicate that PGF2 alpha may play a role in the pathogenesis of bronchial hyperreactivity after airway inflammation. PMID- 1931919 TI - Renal amino acid excretion and aging. AB - The urinary excretion and serum concentration of amino acids were studied in 62 healthy individuals aged 15 to 70 years. In elderly subjects (61-70 years), it was found that renal amino acid clearance per 100 ml GFR (fractional excretion, FE) rose significantly in the following amino acids: CYS, VAL, MET, ILE and LEU. Since the serum concentrations of these amino acids showed no significant changes, but the GFR was reduced, it can be concluded that the raised FE of these amino acids was due to a decrease in their effective tubular reabsorption. A significant correlation was found between FENa and FE of most amino acids including those mentioned above. The findings support the assumption that changes in tubular Na+ transport probably participate in the changes of tubular amino acid transport in elderly individuals. PMID- 1931920 TI - Vascular physiology in Czechoslovakia (1945-1990). PMID- 1931921 TI - The history of renal physiology in Czechoslovakia. PMID- 1931922 TI - Pathophysiology of the pulmonary blood vessels in chronic lung disease. PMID- 1931923 TI - Neuromuscular research in Czechoslovakia. PMID- 1931924 TI - Thermophysiology Research in Czechoslovakia. PMID- 1931925 TI - Developmental physiology and pathophysiology of behaviour and nervous functions. PMID- 1931926 TI - Reallocation of calcium during activation of skeletal muscle cell contraction. PMID- 1931927 TI - Psychophysiology in Czechoslovakia. PMID- 1931929 TI - Physiological and pathological aspects of neuroontogenesis. PMID- 1931928 TI - The endogenous digitalis-like factor. PMID- 1931930 TI - Pain research in Czechoslovakia. PMID- 1931931 TI - Pharmacology of serotonin uptake inhibitors: focus on fluvoxamine. PMID- 1931932 TI - Fluvoxamine: clinical trials and clinical use. PMID- 1931933 TI - Fluvoxamine: an antidepressant for the elderly? PMID- 1931934 TI - Introduction: advances in the pharmacotherapy of depression. PMID- 1931935 TI - Serotonin selectivity for obsessive compulsive and panic disorders. PMID- 1931937 TI - Membrane proteins with soluble counterparts: role of proteolysis in the release of transmembrane proteins. PMID- 1931936 TI - The pharmacotherapy of depression. PMID- 1931938 TI - Structure-function relationships in human lecithin:cholesterol acyltransferase. Site-directed mutagenesis at serine residues 181 and 216. AB - The functions of serine residues at positions 181 and 216 of human plasma lecithin:cholesterol acyltransferase have been studied by site-directed mutagenesis. The serine residue at either site was replaced by alanine, glycine, or threonine in LCAT secreted from stably transfected CHO cells. All substitutions at position 181 gave rise to an enzyme product that was normally secreted but had no detectable catalytic activity. On the other hand, all substitutions at position 216 gave active products, whose activity was fully inhibitable by the serine esterase inhibitor diisopropyl fluorophosphate (DFP). A secondary (although not direct) role for serine-216 was indicated by a 14-fold increase in catalytic rate when this residue was substituted by alanine. Sequence comparison with other lipases suggests that serine-216 may be at or near the hinge of a helical flap displaced following substrate binding. These data strengthen the structural-functional relationship between LCAT and other lipases. PMID- 1931939 TI - Structure of the smooth muscle myosin light-chain kinase calmodulin-binding domain peptide bound to calmodulin. AB - The interaction between the peptide corresponding to the calmodulin-binding domain of the smooth muscle myosin light-chain kinase and (Ca2+)4-calmodulin has been studied by multinuclear and multidimensional nuclear magnetic resonance methods. The study was facilitated by the use of 15N-labeled peptide in conjunction with 15N-edited and 15N-correlated 1H spectroscopy. The peptide forms a 1:1 complex with calcium-saturated calmodulin which is in slow exchange with free peptide. The 1H and 15N resonances of the bound have been assigned. An extensive set of structural constraints for the bound peptide has been assembled from the analysis of nuclear Overhauser effects and three-bond coupling constants. The backbone conformation of the bound peptide has been determined using these constraints by use of distance geometry and related computational methods. The backbone conformation of the peptide has been determined to high precision and is generally indicative of helical secondary structure. Nonhelical backbone conformations are seen in the middle and at the C-terminal end of the bound peptide. These studies provide the first direct confirmation of the amphiphilic helix model for the structure of peptides bound to calcium-saturated calmodulin. PMID- 1931940 TI - Ligand-dependent aggregation and cooperativity: a critique. AB - Ligand-dependent site-site (or subunit-subunit) interactions provide the basis for explaining cooperativity in chemical reactions. Even in the simplest possible nonaggregating system, interpretation of the interactions in terms of structural details requires an explicit assumption (or model) for the binding of the ligand to the sites when there are no interactions. This paper develops in detail the processes by which aggregation will yield ligand-dependent cooperativity. Two conceptually distinct free energy differences may contribute to cooperativity in an aggregation reaction. One is the free energy difference in ligand binding between the monomer and the aggregate. The other is derived from ligand-dependent interactions between the sites of the aggregate. In this analysis an explicit distinction is made between the experimentally accessible constants and those derived from assumed models. Experimental measurements of an aggregation cycle in which all of the species in equilibrium are defined do not allow for an evaluation of the energies of interaction without some model (or assumption). In the analysis presented, an explicit assumption is employed relating the constant for binding of the ligand to the isolated monomer and the constant for the binding of the ligand to aggregate under conditions where there are no ligand dependent interactions. PMID- 1931942 TI - Glucose analogue inhibitors of glycogen phosphorylase: the design of potential drugs for diabetes. AB - The T-state crystal structure of the glucose-phosphorylase b complex has been used as a model for the design of glucose analogue inhibitors that may be effective in the regulation of blood glucose levels. Modeling studies indicated room for additional atoms attached at the C1-beta position of glucose and some scope for additional atoms at the C1-alpha position. Kinetic parameters were determined for alpha-D-glucose: Ki = 1.7 mM, Hill coefficient n = 1.5, and alpha (synergism with caffeine) = 0.2. For beta-D-glucose, Ki = 7.4 mM, n = 1.5, and alpha = 0.4. More than 20 glucose analogues have been synthesized and tested in kinetic experiments. Most were less effective inhibitors than glucose itself and the best inhibitor was alpha-hydroxymethyl-1-deoxy-D-glucose (Ki = 1.5 mM, n = 1.3, alpha = 0.4). The binding of 14 glucose analogues to glycogen phosphorylase b in the crystal has been studied at 2.4-A resolution and the structure have been refined to crystallographic R values of less than 0.20. The kinetic and crystallographic studies have been combined to provide rationalizations for the apparent affinities of glucose and the analogues. The results show the discrimination against beta-D-glucose in favor of alpha-D-glucose is achieved by an additional hydrogen bond made in the alpha-glucose complex through water to a protein group and an unfavorable environment for a polar group in the beta pocket. The compound alpha-hydroxymethyl-1-deoxy-D-glucose has an affinity similar to that of glucose and makes a direct hydrogen bond to a protein group. Comparison of analogues with substituent atoms that have flexible geometry (e.g., 1-hydroxyethyl beta-D-glucoside) with those whose substituent atoms are more rigid (e.g., beta-azidomethyl-1-deoxyglucose or beta-cyanomethyl-1-deoxyglucose) indicates that although all three compounds make similar polar interactions with the enzyme, those with more rigid substituent groups are better inhibitors. In another example, alpha-azidomethyl-1-deoxyglucose was a poor inhibitor. In the crystal structure the compound made several favorable interactions with the enzyme but bound in an unfavorable conformation, thus providing an explanation for its poor inhibition. Attempts to utilize a contact to a buried aspartate group were partially successful for a number of compounds (beta-aminoethyl, beta mesylate, and beta-azidomethyl analogues). The beta pocket was shown to bind gentiobiose (6-O-beta-D-glucopyranosyl-D-glucose), indicating scope for binding of larger side groups for future studies. PMID- 1931944 TI - Direct photoaffinity labeling of gizzard myosin with vanadate-trapped adenosine diphosphate. AB - The active-site topology of smooth muscle myosin has been investigated by direct photoaffinity-labeling studies with [3H]ADP. Addition of vanadate (Vi) and Co2+ enabled [3H]ADP to be stably trapped at the active site (t1/2 greater than 5 days at 0 degrees C). The extraordinary stability of the myosin.Co2+.[3H]ADP.Vi complex allowed it to be purified free of excess [3H]ADP before irradiation began and ensured that only active-site residues became labeled. Following UV irradiation, approximately 10% of the trapped [3H]ADP became covalently attached at the active site. All of the [3H]ADP incorporated into the 200-kDa heavy chain, confirming earlier results using untrapped [alpha-32P]ATP [Maruta, H., & Korn, E. (1981) J. Biol. Chem. 256, 499-502]. After extensive trypsin digestion of labeled subfragment 1, HPLC separation methods combined with alkaline phosphatase treatment allowed two labeled peptides to be isolated. Sequence analysis of both labeled peptides indicated that Glu-185 was the labeled residue. Since Glu-185 has been previously identified as a residue at the active site of smooth myosin using [3H]UDP as a photolabel [Garabedian, T. E., & Yount, R. G. (1990) J. Biol. Chem. 265, 22547-22553], these results provide further evidence that Glu-185, located immediately adjacent to the glycine-rich loop, is located in the purine binding pocket of the active site of smooth muscle myosin. PMID- 1931941 TI - Strong sequence-dependent polymorphism in adduct-induced DNA structure: analysis of single N-2-acetylaminofluorene residues bound within the NarI mutation hot spot. AB - We have used a set of chemical probes to characterize and to compare the structural deformation of double-stranded oligomers bearing a single N-2 acetylaminofluorene (AAF) adduct covalently bound to each of the three guanine residues located within the frameshift mutation hot spot sequence -G1G2CG3CC (NarI site). Two classes of chemical probes have been used, probes that sense the geometry of the helix, giving rise to cuts at every nucleotide (for example, 1,10 phenanthroline-copper), and probes that react with specific bases depending on their conformation (e.g., diethyl pyrocarbonate). For all probes that were tested, a distinct pattern of reactivity was observed according to the position of the adduct within the DNA sequence, revealing an important polymorphism in the adduct-induced DNA structure. With 1,10-phenanthroline-copper at least three base pairs 3' of the AAF-modified guanine were reactive on each strand, showing that the deformation of the DNA helix extends over a region of 4-6 bases pairs centered around the adduct and sensed by the probe in both strands. With the base specific probes, reactivities were limited to the base complementary to the modified guanine and to adjacent bases. Within this sequence context, the three possible AAF adducts have previously been shown to exhibit strong differences in biological responses such as excision repair [Seeberg, E., & Fuchs, R. P. P. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 191-194] and mutagenesis [Burnouf, D., Koehl, P., & Fuchs, R. P. P. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 4147 4151].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931943 TI - Conformational stability, folding, and ligand-binding affinity of single-chain Fv immunoglobulin fragments expressed in Escherichia coli. AB - A fluorescein-binding single-chain Fv (scFv) was chosen as a model for the study of the physicochemical parameters associated with synthetic IgG fragments. Three such scFv proteins were designed from the primary sequences of one anti fluorescyl monoclonal antibody (Mab 4.4.20). These were constructed with varying length interdomain peptide linkers of between 12 and 25 residues, expressed in Escherichia coli, and the protein folding, stability, and antigen-binding characteristics were assessed. Efficient renaturation could be accomplished in vitro to yield approximately 26 mg of active scFv/L of fermentation. Scatchard analysis for fluorescein ligand binding revealed that the scFv designs come within 2-fold of the Ka = 1.99 (+/- 0.18) x 10(9) observed for the parental 4.4.20 Fab and have identical stoichiometries (n approximately 0.99). Reversible solvent denaturation studies demonstrated that the unfolding/refolding equilibria for the scFv proteins can be fit to a simple two-state model and that two of the scFv designs were found to be slightly more stable than single IgG domains (VL and CL) when assessed in terms of the free energy of unfolding, delta Gon-u, or nearly identical to other multiple domain immunoglobulin proteins such as light chains and Fab's when relative transition midpoints, Cm, are compared. Linkers which conferred conformational flexibility beyond the minimally required length of 12 residues were found to have a stabilizing effect. By these criteria of ligand-binding function and protein stability, the scFv proteins were found to be bona fide minimal replicas of their parental IgG molecules. PMID- 1931945 TI - Effect of heme binding on the structure and stability of Escherichia coli apocytochrome b562. AB - The structure and stability of apocytochrome b562 were explored using absorption and circular dichroism spectroscopic methods. The polypeptide chain retains a well-defined structure when the prosthetic heme group is removed from cytochrome b562. Circular dichroism measurements estimate 60% helicity for apocytochrome b562, compared with 80% helicity found in holocytochrome b562. At low pH, apocytochrome b562 displays a midpoint pH of 2.9, while ferricytochrome b562 displays a midpoint pH of 2.3. The unfolding of the apoprotein by urea and heat can be well approximated by the two-state transition model. The stability of apocytochrome b562 is significantly reduced from that of the holoprotein. The free energy of stabilization (delta G degrees) and the midpoint transition temperature (Tm) for apocytochrome b562 are found to be 3.2 +/- 0.5 kcal/mol and 52.3 +/- 0.9 degrees C, respectively, compared with 6.6 +/- 0.5 kcal/mol and 67.2 +/- 0.5 degrees C for ferricytochrome b562. The smaller heat capacity change upon unfolding of apocytochrome b562 than that of ferricytochrome b562, estimated from the thermodynamic parameters, indicates that apocytochrome b562 possesses a smaller hydrophobic core than holocytochrome b562. Size-exclusion chromatography studies indicate that the apoprotein is slightly more extended in molecular dimension than ferricytochrome b562. The data suggest that apocytochrome b562 resembles a "molten globule" or a "collapsed form" of the holoprotein, in which secondary structure formation is largely complete while the global folding is either only partially complete or dynamically expanded. PMID- 1931946 TI - Hydrophobic content and lipid interactions of wild-type and mutant OmpA signal peptides correlate with their in vivo function. AB - Peptides corresponding to the wild-type signal sequence of the Escherichia coli outer membrane protein OmpA and several mutants have been synthesized and characterized biophysically. The mutations were designed collaboratively with Inouye and co-workers to test the understanding of the critical characteristics of signal sequences required for their functions. The in vivo results for these mutants have been reported [Lehnhardt, S., Pollitt, S., & Inouye, M. (1987) J. Biol. Chem. 262, 1716-1719; Goldstein, J., Lehnhardt, S., & Inouye, M. (1990) J. Bacteriol. 172, 1225-1231; Goldstein, J., Lehnhardt, S., & Inouye, M. (1991) J. Biol. Chem. 266, 14413-14417], and the present paper compares the conformational and membrane-interactive properties of six of the OmpA signal peptides. Peptides corresponding to functional OmpA signal sequences in vivo are predominantly alpha helical in membrane-mimetic environments and insert readily into phospholipid bilayers. Nonfunctional OmpA signal peptides may have high helical content but do not penetrate deeply into the acyl chain region of bilayers. The ability of the signal peptides to insert into membranes and their in vivo function correlate with the residue-average hydrophobicity of their hydrophobic cores. The results obtained on OmpA signal peptides parallel closely our previous observations on peptides corresponding to the LamB signal sequence and mutants, arguing that the critical biophysical properties of signal sequences are general despite their lack of primary sequence identity. PMID- 1931947 TI - Contributions of arginines-43 and -94 of human choriogonadotropin beta to receptor binding and activation as determined by oligonucleotide-based mutagenesis. AB - Members of the glycoprotein hormone family contain a common alpha subunit and a hormone-specific beta subunit. Human choriogonadotropin (hCG) beta is a 145 amino acid residue protein glycosylated at 6 positions (2 N-linked and 4 O-linked oligosaccharides). In an effort to elucidate receptor determinants on hCG beta, we have used site-directed mutagenesis to prepare and express several mutant cDNAs with replacements at arginines-43 and -94. Arg-43 is invariant in all known mammalian CG/lutropin beta amino acid sequences, and Arg-94 is conserved in 10 of the 12 sequences. Moreover, various studies involving synthetic peptides and enzymatic digestions of intact beta chains suggest that these residues may be important in hCG receptor binding. Point mutants were made in which these two arginines were replaced with the corresponding residues in human follitropin beta, Leu-43 and Asp-94. The wild-type and mutant beta chains were expressed in CHO cells containing a stably integrated gene for bovine alpha, and heterodimer formation occurred. These heterologous gonadotropins were active in assays using transformed Leydig cells, competitive binding with standard 125I-hCG, and cAMP and progesterone production, but the potency was considerably less than that associated with the hCG beta wild-type-containing gonadotropin. The double-mutant protein Arg-43 to Leu/Arg-94 to Asp also associated with bovine alpha, but the resultant heterodimer exhibited only low activity. Replacement of each arginine with lysine yielded heterodimers that were at least as potent as bovine alpha-hCG beta wild type, but the Lys-43-containing beta chain appeared to exhibit a low degree of subunit association or reduced stability relative to the expressed hCG beta wild type. These results demonstrate that arginines-43 and -94 contribute to receptor binding through a positive charge. PMID- 1931948 TI - Fluorescence study of a mutant cytochrome b5 with a single tryptophan in the membrane-binding domain. AB - Fluorescence studies of cytochrome b5 are complicated by the presence of three tryptophans, at positions 108, 109, and 112, in the membrane-binding domain. The cDNA for rabbit liver cytochrome b5, isolated from a lambda gt11 library, was used to generate a mutated mRNA where the codons for tryptophans-108 and -112 were replaced by codons for leucine. The sequence was expressed in Escherichia coli and the mutant protein was isolated. This mutant protein had the expected absorption spectrum, and its amino acid composition was confirmed by amino acid analysis and by DNA sequencing of the construct. The fluorescence emission spectrum of the mutant is blue-shifted and is narrower than that of the native protein. The quantum yield of the mutant protein, per molecule, is only 60% of that of the native protein, and the enhancement when bound to lipid vesicles or detergent micelles is higher for the mutant. Fluorescence anisotropy measurements and quenching studies using brominated lipids suggest that the fluorescence of the native protein is due to tryptophans-109 and -108 while tryptophan-112 does not emit but undergoes nonradiative energy transfer to tryptophan-108. With this mutant, it was shown that incomplete energy transfer from tyrosines-126 and -129 to tryptophan-109 occurs when the membrane binding domain is inserted into lipid vesicles, which suggests that the membrane-binding domain does not exist in a tight hairpin loop. PMID- 1931949 TI - Mapping the binding domain of a myosin II binding protein. AB - The way in which actin and myosin II become localized to the contractile ring of dividing cells resulting in cleavage furrow formation and cytokinesis is unknown. While much is known about actin binding proteins and actin localization, little is known about myosin localization. A 53-kDa (53K) polypeptide present in the sea urchin egg binds to myosin II in a nucleotide-dependent manner and mediates its solubility in vitro [Yabkowitz, R., & Burgess, D.R. (1987) J. Cell Biol. 105, 927 936]. The binding site of 53K on the myosin molecule was examined in an effort to understand the mechanism of 53K-induced myosin solubility and its potential function in myosin regulation. Blot overlay and chemical cross-linking techniques utilizing myosin proteolytic fragments indicate that 53K binds to fragments proximal to the head-rod junction of myosin. Fragments distal to the head-rod junction do not bind 53K. In addition, the binding of 53K to myosin largely inhibits protease digestion that produces the head and rod fragments. The binding of 53K to the head-rod domain of myosin may be critical in regulation of myosin conformation, localization, assembly, and ATPase activity. PMID- 1931950 TI - Membrane fusion activity of the influenza virus hemagglutinin: interaction of HA2 N-terminal peptides with phospholipid vesicles. AB - We have investigated the interaction of a number of synthetic 20-residue peptides, corresponding to the HA2 N-terminus of the influenza virus hemagglutinin (X31 strain), with phospholipid vesicles and monolayers. Besides the wild-type sequence, two peptides were studied with mutations corresponding to those previously studied in entire HA's expressed in transfected cells [Gething et al., (1986) J. Cell. Biol. 102, 11-23]. These mutations comprised a single Glu replacement for Gly at the N-terminus ("El" mutant) or at position 4 ("E4") of the HA2 subunit and were shown to produce striking alterations in virus-induced hemolysis and syncytia formation, especially for E1. The X31 "wild-type" (wt) peptide and its E4 variant are shown here to have the capacity to insert into phosphatidylcholine (POPC) large unilamellar vesicle (LUV) membranes in a strictly pH-dependent manner, penetration being marginal at pH 7.4 and significant at pH 5.0. Bilayer insertion was evident from a shift in the intrinsic Trp fluorescence of the wt and E4 peptides and from the induction of calcein leakage from POPC LUV and correlated well with the peptides' ability at pH 5.0 to penetrate into POPC monolayers at initial surface pressures higher than 30 mN/m. By contrast, the E1 peptide was found, at pH 5.0, to bind less tightly to vesicles (assessed by a physical separation method) and to cause much less leakage of POPC LUV than the wt, even under conditions where the peptides were bound to approximately the same extent. Consistent with the correlation between leakage and penetration observed for the wt peptide at pH 5 versus 7, the E1 peptide, even at low pH, showed much less lipid-vesicle-induced shift of its Trp fluorescence than wt, caused a much slower rate of leakage of vesicle contents, and did not insert into POPC monolayers at surface pressures beyond 28.5 mN/m. Circular dichroism spectroscopy measurements of peptides in POPC SUV showed that the conformations of all three peptides are sensitive to pH, but only the wt and E4 peptides became predominantly alpha-helical at acid pH. PMID- 1931951 TI - Breakdown of the photosystem II reaction center D1 protein under photoinhibitory conditions: identification and localization of the C-terminal degradation products. AB - Illumination of a suspension of thylakoids with light at high intensity causes inhibition of the photosystem II electron transport activity and loss from the membrane of the D1 protein of the photosystem II reaction center. Impairment of the electron transport activity and depletion of D1 protein from the thylakoid membrane of pea were investigated with reference to the presence or absence of oxygen in the suspension. The breakdown products of the D1 protein were identified by immunoblotting with anti-D1 polyclonal antibodies which were proven to recognize mainly the C-terminal region of the protein. The results obtained show that (i) the light-induced inactivation of the photosystem II electron transport activity under anaerobic conditions is faster than in the presence of oxygen; (ii) depletion of D1 protein is observed on a longer time scale with respect to loss of electron transport activity and is faster when photoinhibition is performed in the presence of oxygen; (iii) C-terminal fragments of D1 are only observed when photoinhibition is carried out anaerobically and are mainly localized in the stroma-exposed regions; and (iv) the fragments observed after anaerobic photoinhibition are quickly degraded on further illumination of the thylakoid suspension in the presence of oxygen. PMID- 1931952 TI - Comparative NMR studies on cardiac troponin C and a mutant incapable of binding calcium at site II. AB - One- and two-dimensional NMR techniques were used to study both the influence of mutations on the structure of recombinant normal cardiac troponin C (cTnC3) and the conformational changes induced by Ca2+ binding to site II, the site responsible for triggering muscle contraction. Spin systems of the nine Phe and three Tyr residues were elucidated from DQF-COSY and NOESY spectra. Comparison of the pattern of NOE connectivities obtained from a NOESY spectrum of cTnC3 with a model of cTnC based on the crystal structure of skeletal TnC permitted sequence specific assignment of all three Tyr residues, as well as Phe-101 and Phe-153. NOESY spectra and calcium titrations of cTnC3 monitoring the aromatic region of the 1H NMR spectrum permitted localization of six of the nine Phe residues to either the N- or C-terminal domain of cTnC3. Analysis of the downfield-shifted C alpha H resonances permitted sequence-specific assignment of those residues involved in the beta-strand structures which are part of the Ca(2+)-binding loops in both the N- and C-terminal domains of cTnC3. The short beta-strands in the N terminal domain of cTnC3 were found to be present and in close proximity even in the absence of Ca2+ bound at site II. Using these assignments, we have examined the effects of mutating Asp-65 to Ala, CBM-IIA, a functionally inactive mutant which is incapable of binding Ca2+ at site II [Putkey, J.A., Sweeney, H. L., & Campbell, S. T. (1989) J. Biol. Chem. 264, 12370]. Comparison of the apo, Mg(2+) , and Ca(2+)-bound forms of cTnC3 and CBM-IIA demonstrates that the inability of CBM-IIA to trigger muscle contraction is not due to global structural changes in the mutant protein but is a consequence of the inability of CBM-IIA to bind Ca2+ at site II. The pattern of NOEs between aromatic residues in the C-terminal domain is nearly identical in cTnC3 and CBM-IIA. Similar interresidue NOEs were also observed between Phe residues assigned to the N-terminal domain in the Ca(2+)-saturated forms of both cTnC3 and CBM-IIA. However, chemical shift changes were observed for the N-terminal Phe residues in CBM-IIA. This suggests that binding of Ca2+ to site II alters the chemical environment of the residues in the N-terminal hydrophobic cluster without disrupting the spatial relationship between the Phe residues located in helices A and D. PMID- 1931953 TI - Kinetics and regulation of two catalytic subunits of cAMP-dependent protein kinase from Aplysia californica. AB - CAPL-A1 and CAPL-A2, two catalytic subunits of Aplysia cAMP-dependent protein kinase, are encoded by mRNAs generated by alternative splicing of transcripts of a gene that contains two mutually exclusive exon cassettes. The subunits are identical except for amino acids 142-183 of the 352 residues, which differ at 10 of 42 positions. CAPL-A1 and CAPL-A2 have now been expressed in insect cells and purified to homogeneity. The subunits differ in their catalytic properties, which have been determined with a series of synthetic peptide substrates. For example, kcat and Km values for the peptide LRRASLG (kemptide) are 42 s-1 and 36 microM and 28 s-1 and 17 microM for CAPL-A1 and CAPL-A2, respectively. CAPL-A1 and CAPL A2 have different substrate specificities. For example, (kcat/Km)peptide T/(kcat/Km)kemptide is 9.1 x 10(-3) for CAPL-A1 and 15 x 10(-3) for CAPL-A2, where peptide-T is the kemptide homologue LRRATLG. The subunits also differ in regulation as determined by their interactions with a purified type I regulatory subunit, which has an IC50 for CAPL-A1 that is 3.5 times higher than the IC50 for CAPL-A2. These modest differences reinforce accumulating evidence that the physiological state of a cell depends upon a spectrum of protein kinases with overlapping substrate specificities and regulatory properties. PMID- 1931954 TI - Active-site-directed specific competitive inhibitors of phospholipase A2: novel transition-state analogues. AB - More than 100 amphiphilic phosphoesters, possible tetrahedral transition-state analogues capable of coordinating to the calcium ion at the active site of phospholipase A2, were designed, synthesized, and tested as inhibitors for the hydrolysis of 1,2-dimyristoyl-sn-glycero-3-phosphomethanol vesicles in the scooting mode. This assay system permits the study of structurally diverse inhibitors with phospholipase A2S from different sources, and it is not perturbed by factors that change the quality of the interface. As a prototype, 1-hexadecyl 3-trifluoroethylglycero-2-phosphomethanol (MJ33) was investigated in detail. Only the (S)-(+) analogue of MJ33 is inhibitory, and it is as effective as the sn-2 phosphonate or the sn-2 amide analogues of sn-3 phospholipids. The inhibitory potencies of the various phosphoesters depended strongly on the stereochemical and structural features, and the mole fractions of inhibitors required for 50% inhibition, X1(50), ranged from more than 1 to less than 0.001 mole fraction. The affinity of certain inhibitors for enzymes from different sources differed by more than 200-fold. The inhibitors protected the catalytic site residue His-48 from alkylation in the presence of calcium but not barium as expected if the formation of the EI complex is supported only by calcium. The equilibrium dissociation constant for the inhibitor bound to the enzyme at the interface was correlated with the XI(50) values, which were different if the inhibition was monitored in the pseudo-zero-order or the first-order region of the progress curve. These results show that the inhibitors described here interfered only with the catalytic turnover by phospholipase A2's bound to the interface, their binding to the enzyme occurred through calcium, and the inhibitors did not have any effect on the dissociation of the enzyme bound to the interface. PMID- 1931955 TI - Keto fatty acids not containing doubly allylic methylenes are lipoxygenase substrates. AB - The soybean lipoxygenase I oxygenates the unusual substrate 12-keto-(9Z) octadecenoic acid methyl ester as indicated by oxygen uptake and spectral changes of the incubation mixture. The main oxygenation products have been isolated by HPLC and identified as 9,12-diketo-(10E)-octadecenoic acid methyl ester and 12 keto-(10E)-dodecenoic acid methyl ester by UV and IR spectroscopy, cochromatography with an authentic standard, gas chromatography/mass spectroscopy, and 1H NMR. In the formation of both compounds the oxygenase and hydroperoxidase activities of the enzyme appear to be involved. These data and the earlier results on the oxygenation of furanoic fatty acids (Boyer et al., 1979) indicate that the lipoxygenase reaction is not restricted to substrates containing a 1,4-pentadiene structure. PMID- 1931956 TI - Kinetic characterization of the calmodulin-activated catalytic subunit of phosphorylase kinase. AB - The phosphorylase kinase holoenzyme from skeletal muscle is composed of a catalytic and three different regulatory subunits. Analysis of the kinetic mechanism of the holoenzyme is complicated because both the natural substrate phosphorylase b and also phosphorylase kinase itself have allosteric binding sites for adenine nucleotides. In the case of the kinase, these allosteric sites are not on the catalytic subunit. We have investigated the kinetic mechanism of phosphorylase kinase by using its isolated catalytic gamma-subunit (activated by calmodulin) and an alternative peptide substrate (SDQEKRKQISVRGL) corresponding to the convertible region of phosphorylase b, thus eliminating from our system all known allosteric binding sites for nucleotides. This peptide has been previously employed to study the kinetic mechanism of the kinase holoenzyme before the existence of the allosteric sites on the regulatory subunits was suspected [Tabatabai, L. B., & Graves, D. J. (1978) J. Biol. Chem. 253, 2196 2202]. This peptide was determined to be as good an alternative substrate for the isolated catalytic subunit as it was for the holoenzyme. Initial velocity data indicated a sequential kinetic mechanism with apparent Km's for MgATP and peptide of 0.07 and 0.47 mM, respectively. MgADP used as product inhibitor showed competitive inhibition against MgATP and noncompetitive inhibition against peptide, whereas with phosphopeptide as product inhibitor, the inhibition was competitive against both MgATP and peptide. The initial velocity and product inhibition studies were consistent with a rapid equilibrium random mechanism with one abortive complex, enzyme-MgADP-peptide. The substrate-directed, dead-end inhibitors 5'-adenylyl imidodiphosphate and Asp-peptide, in which the convertible Ser of the alternative peptide substrate was replaced with Asp, were competitive inhibitors toward their like substrates and noncompetitive inhibitors toward their unlike substrates, further supporting a random mechanism, which was also the conclusion from the report cited above that used the holoenzyme. PMID- 1931957 TI - Synergistic effect of histone H1 and nucleolin on chromatin condensation in mitosis: role of a phosphorylated heteromer. AB - Repeated motifs, rich in basic residues, are characteristic of both the N terminal domain of the nucleolus-specific protein, nucleolin, and the second half of the C-terminal domain of histone H1. These repeats are also the target for phosphorylation by the mitosis-specific p34cdc2 kinase. We have previously shown that synthetic peptides [(KTPKKAKKP)2 for histone H1 and (ATPAKKAA)2 for nucleolin] corresponding to these two repeated motifs are able to act in synergy to induce DNA hypercondensation (Erard et al., 1990). In order to determine the molecular basis of this synergistic interaction, we have studied the condensation of the homopolymer poly(dA).poly(dT) in the presence of the two synthetic peptides. Circular dichroism has been used to monitor the psi (+)-type condensation and has revealed that phosphorylation enhances the synergistic effect of the two peptides. Analysis of different combinations of the two peptides suggests that there is a direct interaction between them which is stabilized by phosphorylation. Furthermore, there is a striking correlation between the degree of homopolymer condensation and the stability of the heteromeric complex. Phosphorylation takes place on the threonine residues on the repeat motifs within a region which is likely to adopt a beta-turn structure. Circular dichroism and infrared spectroscopy provide evidence that phosphorylation stabilizes the beta-turn structure of both peptides, and computer modeling shows that this may be due to steric hindrance imposed by the phosphate group. We suggest that phosphorylated nucleolin and histone H1 interact through their homologous domain structured in beta-spirals in order to condense certain forms of DNA during mitosis. PMID- 1931958 TI - Synthesis and expression in Escherichia coli of a gene for kappa-bungarotoxin. AB - A gene which codes for the 66-residue polypeptide of kappa-bungarotoxin has been chemically synthesized by linking together 3 synthetic double-stranded oligonucleotides in a bacterial plasmid. The synthesis incorporated six unique silent restriction sites spaced throughout the gene for use in cassette mutagenesis. Direct expression of the kappa-bungarotoxin polypeptide by itself in Escherichia coli failed to result in a stable product. The toxin polypeptide was stabilized and expressed in E. coli as part of a fusion protein with rat intestinal fatty acid binding protein under control of the nalidixic acid inducible recA promoter. Two fusion protein constructs were prepared that differed only in the cleavage site between the fatty acid binding protein and the toxin polypeptide. One contained a factor Xa cleavage site, and the other, since the toxin itself is devoid of methionine, contained a methionyl residue that served as a cyanogen bromide cleavage site. The fusion proteins were isolated by ion-exchange chromatography and reverse-phase HPLC. The construct containing the factor Xa cleavage site could not be cleaved under nondenaturing conditions. On the other hand, kappa-bungarotoxin was efficiently cleaved from the methionyl fusion protein with CNBr. The toxin polypeptide was isolated by reverse-phase HPLC and ion-exchange chromatography and produced a complete and specific blockade of neuronal nicotinic acetylcholine receptors in chick ciliary ganglia which was indistinguishable from that produced by a comparable amount of venom purified kappa-bungarotoxin. PMID- 1931959 TI - The coagulation cascade: initiation, maintenance, and regulation. PMID- 1931960 TI - The C-terminus of tissue factor pathway inhibitor is essential to its anticoagulant activity. AB - Tissue factor pathway inhibitor (TFPI) from different cell lines shows up to 15 fold differences in the ratio of anticoagulant to chromogenic activity. The anticoagulant activity was dependent on the purification procedure used and it was possible to isolate two fractions of recombinant TFPI. Only one of these fractions showed anticoagulant activity comparable with TFPI from normal human plasma, and Western blotting showed that the low-activity fraction did not react with an antibody raised against a peptide of TFPI located near the C-terminal. Analysis by mass spectroscopy of peptides from V8 protease digests showed that C terminal amino acids could only be identified from the high-activity form, while heterologous fragmentation had taken place in the form with low anticoagulant activity. Previously published studies on TFPI have been performed using material of low anticoagulant activity compared with plasma TFPI, and we suggest that these studies have been performed with material degraded in the C-terminus. PMID- 1931961 TI - Molecular cloning of putative odorant-binding and odorant-metabolizing proteins. AB - Olfactory reception occurs via the interaction of odorants with the chemosensory cilia of the olfactory receptor cells located in the nasal epithelium. The cDNA clones from mRNA specific to olfactory mucosa were studied. One of these clones, OBPII, encodes a secretory protein with significant homology to odorant-binding protein (OBP), a protein with broad odorant-binding ability, and is expressed in the lateral nasal gland, which is the site of expression of OBP. The OBPII sequence also shows significant homology to the VEG protein, which is thought to be involved in taste transduction. OBPII is a new member of the lipophilic molecule carrier protein family. The second cDNA clone encodes a novel homologue of glutathione peroxidase, an enzyme involved in cellular biotransformation pathways. Its expression appears to be localized to the Bowman's glands, the site of several previously identified olfactory-specific biotransformation enzymes. PMID- 1931962 TI - An unusual peptide conformation may precipitate amyloid formation in Alzheimer's disease: application of solid-state NMR to the determination of protein secondary structure. AB - The formation of insoluble proteinaceous deposits is characteristic of many diseases which are collectively known as amyloidosis. There is very little molecular-level structural information available regarding the amyloid deposits due to the fact that the constituent proteins are insoluble and noncrystalline. Therefore, traditional protein structure determination methods such as solution NMR and X-ray crystallography are not applicable. We report herein the application of the solid-state NMR technique rotational resonance (R2) to the accurate measurement of carbon-to-carbon distances in the amyloid formed from a synthetic fragment (H2N-LeuMetValGlyGlyValValIleAla-CO2H) of the amyloid-forming protein of Alzheimer's disease (AD). This sequence has been implicated in the initiation of amyloid formation. Two distances measured by R2 indicate that an unusual structure, probably involving a cis amide bond, is present in the aggregated peptide amyloid. This structure is incompatible with the accepted models of fibril structure. A relationship between this structure and the stability of the amyloid is proposed. PMID- 1931963 TI - Structural basis for broad specificity in alpha-lytic protease mutants. AB - Binding pocket mutants of alpha-lytic protease (Met 192----Ala and Met 213--- Ala) have been constructed recently in an effort to create a protease specific for Met just prior to the scissile bond. Instead, mutation resulted in proteases with extraordinarily broad specificity profiles and high activity [Bone, R., Silen, J. L., & Agard, D. A. (1989) Nature 339, 191-195]. To understand the structural basis for the unexpected specificity profiles of these mutants, high resolution X-ray crystal structures have been determined for complexes of each mutant with a series of systematically varying peptidylboronic acids. These inhibitory analogues of high-energy reaction intermediates provide models for how substrates with different side chains interact with the enzyme during the transition state. Fifteen structures have been analyzed qualitatively and quantitatively with respect to enzyme-inhibitor hydrogen-bond lengths, buried hydrophobic surface area, unfilled cavity volume, and the magnitude of inhibitor accommodating conformational adjustments (particularly in the region of another binding pocket residue, Val 217A). Comparison of these four parameters with the Ki of each inhibitor and the kcat and Km of the analogous substrates indicates that while no single structural parameter consistently correlates with activity or inhibition, the observed data can be understood as a combination of effects. Furthermore, the relative contribution of each term differs for the three enzymes, reflecting the altered conformational energetics of each mutant. From the extensive structural analysis, it is clear that enzyme flexibility, especially in the region of Val 217A, is primarily responsible for the exceptionally broad specificity observed in either mutant. Taken together, the observed patterns of substrate specificity can be understood to arise directly from interactions between the substrate and the residues lining the specificity pocket and indirectly from interactions between peripheral regions of the protein and the active-site region that serve to modulate active-site flexibility. PMID- 1931964 TI - Structural and functional correlates of sucrase-alpha-dextrinase in intact brush border membranes. AB - The structure and catalytic function of rat intestinal sucrase-alpha-dextrinase (sucrase-isomaltase) were characterized in intact brush border membranes by differential denaturation in 1% SDS at 4, 37, 45, 55, and 100 degrees C, analysis by acrylamide electrophoresis, and subsequent renaturation by transfer to nitrocellulose and in situ analyses of immunoactivity and catalytic activity (immunoblotting and catalytic blotting). Both the sucrase and alpha-dextrinase activities were associated with two mature oligomers, with sucrase predominantly in a 250-260-kDa unit and dextrinase in a 330-350-kDa unit. While sucrase activity declined progressively in response to increasing temperature to 45 degrees C due to loss of active sites, alpha-dextrinase activity increased reciprocally (Vmax +176%). Three principal monomeric products of postinsertional processing comprise the oligomers: alpha, 140 kDa, which carries the sucrase active site; beta, 125 kDa, harboring the dextrinase active site; and gamma, 110 kDa, produced by removal of 185 amino acid residues from the N-terminus of the alpha. Rather than being a simple hybrid dimer, membrane-associated sucrase-alpha dextrinase appears to consist of two major oligomeric forms having complex structural associations that dramatically affect the availability of the active catalytic sites at the brush border membrane surface. PMID- 1931965 TI - Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. AB - Vancomycin resistance in Enterococcus faecium BM4147 is mediated by vancomycin resistance proteins VanA and VanH. VanA is a D-alanine:D-alanine ligase of altered substrate specificity [Bugg, T. D. H., Dutka-Malen, S., Arthur, M., Courvalin, P., & Walsh, C. T. (1991) Biochemistry 30, 2017-2021], while the sequence of VanH is related to those of alpha-keto acid dehydrogenases [Arthur, M., Molinas, C., Dutka-Malen, S., & Courvalin, P. (1991) Gene (submitted)]. We report purification of VanH to homogeneity, characterization as a D-specific alpha-keto acid dehydrogenase, and comparison with D-lactate dehydrogenases from Leuconostoc mesenteroides and Lactobacillus leichmanii. VanA was found to catalyze ester bond formation between D-alanine and the D-hydroxy acid products of VanH, the best substrate being D-2-hydroxybutyrate (Km = 0.60 mM). The VanA product D-alanyl-D-2-hydroxybutyrate could then be incorporated into the UDPMurNAc-pentapeptide peptidoglycan precursor by D-Ala-D-Ala adding enzyme from Escherichia coli or by crude extract from E. faecium BM4147. The vancomycin binding constant of a synthetic modified peptidoglycan analogue N-acetyl-D-alanyl D-2-hydroxybutyrate (Kd greater than 73 mM) was greater than 1000-fold higher than the binding constant for N-acetyl-D-alanyl-D-alanine (Kd = 54 microM), partly due to the disruption of a hydrogen bond in the vancomycin-target complex, thus providing a molecular rationale for high-level vancomycin resistance. PMID- 1931966 TI - Expression and mutagenesis of human poly(ADP-ribose) polymerase as a ubiquitin fusion protein from Escherichia coli. AB - The cDNA of human poly(ADP-ribose) polymerase (pADPRP), encoding the entire protein, was subcloned into the Escherichia coli expression plasmid pYUb. In this expression system, the carboxyl terminus of ubiquitin is fused to the amino terminus of a target protein, in this case pADPRP, stabilizing the accumulation of the cloned gene product. Following induction of the transformed cells, the sonicated extract contained a unique protein immunoreactive with both pADPRP and ubiquitin antibodies and corresponding to the predicted mobility of the fusion protein in SDS-PAGE. Fusion of ubiquitin to pADPRP increased the yield of pADPRP approximately 10-fold compared to that of the unfused enzyme. The resulting recombinant fusion protein had catalytic properties which were nearly identical to those of native pADPRP obtained from mammalian tissues. These properties included specific activity, Km for NAD, response to DNA strand breaks, response to Mg2+, inhibition by 3-aminobenzamide, and activity in activity gel analysis. An initial analysis by deletion mutagenesis of pADPRP's functional domains revealed that deletions in the NAD binding domain eliminated all activity; however, partial polymerase activity resulted from deletion in the DNA binding or automodification domains. The activities were not enhanced by breaks in DNA. We further report a colony filter screening procedure designed to identify functional polymerase molecules which will facilitate structure/function studies of the polymerase. PMID- 1931967 TI - Folding of chymotrypsin inhibitor 2. 1. Evidence for a two-state transition. AB - The reversible folding and unfolding of barley chymotrypsin inhibitor 2 (CI2) appears to be a rare example in which both equilibria and kinetics are described by a two-state model. Equilibrium denaturation by guanidinium chloride and heat is completely reversible, and the data can be fitted to a simple two-state model involving only native and denatured forms. The free energy of folding in the absence of denaturant, delta GH2O, at pH 6.3, is calculated to be 7.03 +/- 0.16 and 7.18 +/- 0.43 kcal mol-1 for guanidinium chloride and thermal denaturation, respectively. Scanning microcalorimetry shows that the ratio of the van't Hoff enthalpy of denaturation to the calorimetric enthalpy of denaturation does not deviate from unity, the value observed for a two-state transition, over the pH range 2.2-3.5. The heat capacity change for denaturation is found to be 0.789 kcal mol-1 K-1. The rate of unfolding of CI2 is first order and increases exponentially with increasing guanidinium chloride concentration. Refolding, however, is complex and involves at least three well-resolved phases. The three phases result from heterogeneity of the unfolded form due to proline isomerization. The fast phase, 77% of the amplitude, corresponds to the refolding of the fraction of the protein that has all its prolines in a native trans conformation. The rate of this major phase decreases exponentially with increasing guanidinium chloride concentration. The unfolding and refolding kinetics can also be fitted to a two-state model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931968 TI - Folding of chymotrypsin inhibitor 2. 2. Influence of proline isomerization on the folding kinetics and thermodynamic characterization of the transition state of folding. AB - The refolding of chymotrypsin inhibitor 2 (CI2) is, at least, a triphasic process. The rate constants are 53 s-1 for the major phase (77% of the total amplitude) and 0.43 and 0.024 s-1 for the slower phases (23% of the total amplitude) at 25 degrees C and pH 6.3. The multiphase nature of the refolding reaction results from heterogeneity in the denatured state because of proline isomerization. The fast phase corresponds to the refolding of the fraction of protein that has all its prolines in a native trans conformation in the denatured state. It is not catalyzed by peptidyl-prolyl isomerase. The rate-limiting step of folding for the slower phases, however, is proline isomerization, and they are both catalyzed by peptidyl-prolyl isomerase. The slowest phase has properties consistent with a process involving proline isomerization in a denatured state. In particular, the activation enthalpy is large, 16 kcal mol-1 K-1, and the rate is independent of guanidinium chloride concentration ([GdnHCl]). In comparison, the intermediate phase shows properties consistent with a process involving proline isomerization in a partially structured state. The activation enthalpy is small, 8 kcal mol-1 K-1, and the rate has a strong dependence on [GdnHCl]. Temperature dependences of the rate constants for unfolding and for the fast refolding phase, both in the absence and in the presence of GdnHCl, were used to characterize the thermodynamic nature of the transition state and its relative exposure to solvent. The Eyring plot for unfolding is linear, indicating that there is relatively little change in heat capacity between native state and transition state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931969 TI - Solution conformation of salmon calcitonin in sodium dodecyl sulfate micelles as determined by two-dimensional NMR and distance geometry calculations. AB - The 32 amino acid hormone salmon calcitonin was studied at pH 3.7 and 7.4 by two dimensional NMR in sodium dodecyl sulfate (SDS) micelles at 310 K. The spectrum was fully assigned, and the secondary structure was obtained from nuclear Overhauser enhancement spectroscopy (NOESY), 3JHN alpha coupling constants, and slowly exchanging amide data. Three-dimensional structures consistent with NMR data were generated by using distance geometry calculations. A set of 260 interproton distances, derived from NOESY, and hydrogen-bond constraints, obtained from analysis of the amide exchange, were used. From the initial random conformations, 13 distance geometry structures with minimal violations were selected for further refinement with restrained energy minimization. In SDS, at both pHs, the main conformational feature of the hormone is an alpha-helix from Thr6 through Tyr22, thus including the amphipathic 8-22 segment and two residues of the Cys1-Cys7 N-terminal loop. The C-terminal decapeptide forms a loop folded back toward the helix. The biological significance of this conformation is discussed. PMID- 1931970 TI - Complete amino acid sequence of human liver cytosolic alanine aminotransferase (GPT) determined by a combination of conventional and mass spectral methods. AB - The complete amino acid sequence of human liver cytosolic alanine aminotransferase (GPT) (EC 2.6.1.2) is presented. Two primary sets of overlapping fragments were obtained by cleavage of the pyridylethylated protein at methionyl and lysyl bonds with cyanogen bromide and Achromobacter protease I, respectively. Isolated peptides were analyzed with a protein sequencer or with a plasma desorption time of flight mass spectrometer and placed in the sequence on the basis of their molecular mass and homology to the sequence of rat GPT. The protein was found to be acetylated at the amino terminus and contained 495 amino acid residues. The Mr of the subunit was calculated to be 54,479, which was in good agreement with a Mr of 55,000 estimated by SDS-PAGE, and also indicated that the active enzyme with a Mr of 114,000 was a homodimer composed of two identical subunits. The amino acid sequence is highly homologous to that of rat GPT (87.9% identity) recently determined [Ishiguro, M., Suzuki, M., Takio, K., Matsuzawa, T., & Titani, K. (1991) Biochemistry 30, 6048-6053]. All of the crucial amino acid residues are conserved in human GPT, which seem to be hydrogen bonding to pyridoxal 5'-phosphate in rat GPT by the sequence homology to other alpha aminotransferases with known tertiary structures. PMID- 1931971 TI - Comparison of alpha-lactalbumin and lysozyme using vibrational circular dichroism. Evidence for a difference in crystal and solution structures. AB - The conformation of the milk protein alpha-lactalbumin has been studied using vibrational circular dichroism (VCD) and compared to parallel studies on lysozyme. These proteins have been shown by Acharya et al. [(1989) J. Mol. Biol. 208, 99-127] to have very similar three-dimensional crystal structures. However, their VCD spectra in D2O solution are quite different. The VCD of lysozyme in D2O more resembles that of alpha-lactalbumin in 33% propanol/D2O, under which conditions alpha-lactalbumin has conformationally transformed to a structure with increased helical fraction. These results can be seen to be consistent with UVCD and resolution-enhanced FTIR spectra of alpha-lactalbumin and lysozyme in both D2O and H2O environments. The solvent sensitivity of the alpha-lactalbumin spectra and hence of its conformation contrasted with the lack of such sensitivity for lysozyme suggest that the alpha-lactalbumin crystal structure represents a conformation different from that which is dominant in aqueous solution. PMID- 1931972 TI - Estrogen-induced ribonuclease activity in Xenopus liver. AB - Estrogen administration to male Xenopus causes the cytoplasmic destabilization of the hepatic serum protein coding mRNAs, most notably, albumin, yet has little effect on mRNAs encoding intracellular proteins such as ferritin. This report describes an estrogen-inducible ribonuclease activity found in liver polysomes that degrades albumin mRNA 4 times faster in vitro than it degrades ferritin mRNA. This differential rate of degradation was observed upon incubation of polysome extract with free liver RNA, isolated liver mRNPs, or transcripts from plasmid vectors. A cleavage fragment consisting of a doublet of approximately 194 nucleotides in length was consistently observed upon digestion of transcripts for the full length or 5' half of albumin mRNA. The generation of this cleavage fragment was used as an assay to study properties of the polysome nuclease activity. The 194 doublet is produced by the action of a Mg(2+)-independent endonuclease. This distinguishes the Xenopus liver enzyme from the enzymes that degrade histone or c-myc mRNA in vitro. It is inactivated by 400 mM NaCl or heating at 90 degrees C, but not by placental ribonuclease inhibitor or N ethylmaleimide. Finally, the polysomal nuclease activity does not degrade double stranded RNA. We believe the estrogen-induced nuclease activity contains an enzyme(s) that may mediate hormone-regulated changes in mRNA stability in this tissue. PMID- 1931973 TI - Vitamin K dependent carboxylation: determination of the stereochemical course using 4-fluoroglutamyl-containing substrate. AB - The stereochemical course of the vitamin K dependent carboxylation has been elucidated using a (4S)-4-fluoroglutamyl-containing pentapeptide as a substrate. The absolute configuration of the [13C]-4-carboxy-4-fluoroglutamate obtained when the carboxylation was carried out with 13C-labeled sodium bicarbonate, was determined after reduction of the [13C]-4-carboxy-4-fluoroglutamyl residue into 4 fluoro-5,5'-dihydroxyleucine, hydrolysis, lactonization, and peracetylation. The absolute configuration at C-4 was determined to be S by locating the 13C label in the lactone ring of the trans isomeric lactone and in the hydroxymethyl group of the cis isomer following HPLC separation of both isomers and analysis by GC/MS/MS techniques. It follows that the vitamin K dependent carboxylation occurs with inversion of configuration. PMID- 1931974 TI - Characterization of a major brain tubulin variant which cannot be tyrosinated. AB - Brain tubulin preparations contain an abundant type of tubulin which does not undergo the normal cycle of tyrosination-detyrosination, and whose nature is still unknown. We have used peptide sequence analysis and mass spectrometry combined with immunological procedures to show that this non-tyrosinatable tubulin has a specific primary structure. It differs from the tyrosinated isotype in that it lacks a carboxy-terminal glutamyl-tyrosine group on its alpha-subunit. Thus, non-tyrosinatable tubulin originates from a well-defined posttranslational modification of the tubulin primary structure which is located at the expected site of activity of tubulin tyrosine ligase. This probably accounts for the reason why it cannot be tyrosinated. The significance of this abundant brain isotubulin and the metabolic pathway involved in its formation remain to be elucidated. This should shed light on the relation between the structural diversity of the carboxy terminus of alpha-tubulin and the regulation of functional properties of microtubules. PMID- 1931975 TI - Modulation of protein 4.1 binding to inside-out membrane vesicles by phosphorylation. AB - The effect of phosphorylation on the binding of protein 4.1 to erythrocyte inside out vesicles was investigated. Protein 4.1 was phosphorylated with casein kinase A, protein kinase C, and cAMP-dependent protein kinase. An analysis of the phosphopeptides generated by alpha-chymotryptic and tryptic digestion indicates these kinases phosphorylate similar as well as distinct domains within protein 4.1. All three enzymes catalyze the phosphorylation to varying degrees of the 46 , 16-, and 8-10-kDa fragments derived from limited chymotryptic cleavage. In addition, casein kinase A phosphorylates a 24-kDa domain, whereas protein kinase C phosphorylates a 30-kDa domain. Protein 4.1 phosphorylated by casein kinase A and protein kinase C, but not cAMP-dependent protein kinase, exhibits a reduced binding to KI-extracted inside-out vesicles. On the other hand, phosphorylation of inside-out vesicles by casein kinase A does not affect their ability to bind protein 4.1. The inside-out vesicles, however, inhibit the phosphorylation of protein 4.1 by casein kinase A and protein kinase C, but not by cAMP-dependent protein kinase. These results suggest that casein kinase A and protein kinase C may modulate the binding of protein 4.1 to the membrane by phosphorylation of specific domains of the cytoskeletal protein. Since the 30-kDa domain has been suggested as a membrane-binding site, that phosphorylation by protein kinase C reduces the binding of protein 4.1 to inside-out vesicles is perhaps not surprising. On the other hand, the role of the casein kinase A substrate 24-kDa domain in membrane binding has not been established and needs to be examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931976 TI - Glycopeptidolipids from Mycobacterium fortuitum: a variant in the structure of C mycoside. AB - Strains from the Mycobacterium fortuitum complex contain surface species-specific lipids allowing their precise identification. In M. fortuitum biovar. peregrinum two major glycopeptidolipids, of the C-mycoside type, were characterized by a combination of chemical analyses, NMR, and FAB mass spectrometry. Important information was obtained by mass spectrometry both on their molecular weight and on the peptide and saccharide sequences without any derivatization. The basic structure of the two compounds was shown to be [formula: see text] The disaccharide part linked O-glycosidically to alaninol was either 3,4-di-O-methyl alpha-L-rhamnopyranosyl (1----2) 3,4-di-O-methyl-alpha-L-rhamnopyranoside (mycoside I) or 3-O-methyl-alpha-L-rhamnopyranosyl (1----2) 3,4-di-O-methyl-alpha L-rhamnopyranoside (mycoside II). This is an unusual structure of a C-mycoside since neither 6-deoxytalose nor its derivatives are present. Moreover, the oligosaccharide part is linked to the alaninol residue instead of the allo threonine. PMID- 1931977 TI - Effect of calcium on the dynamic behavior of sialylglycerolipids and phospholipids in mixed model membranes. A 2H and 31P NMR study. AB - DTSL, a sialic acid bearing glyceroglycolipid, has been deuteriated at the C3 position of the sialic acid headgroup and at the C3 position of the glycerol backbone. The glycolipid was studied as a neat dispersion and in multilamellar dispersions of DMPC (at a concentration of 5-10 mol % relative to phospholipid), using 2H and 31P NMR. The quadrupolar splittings, delta v Q, of the headgroup deuterons were found to differ in the neat and mixed dispersion, suggesting different headgroup orientations in the two systems. In DTSL-DMPC liposomes, two quadrupolar splittings were observed, indicating that the axial and equatorial deuterons make different angles with respect to the axis of motional averaging. The splittings originating from the equatorial and axial deuterons were found to increase and decrease with increasing temperature, respectively, indicating a temperature-dependent change in average headgroup orientation. Longitudinal relaxation times, T1Z, were found to be short (3-6 ms). The field dependence of T1Z suggests that more than one motion governs relaxation. At 30.7 MHz a T1Z minimum was observed at approximately 40 degrees C. At 46.1 MHz the T1Z values were longer and increased with temperature, demonstrating that the dominant rigid body motions of the headgroup at this field are in the rapid motional regime (greater than 10(8) s-1). DTSL labeled at the glycerol C3 position was studied in DMPC multilamellar dispersions. Whereas two quadrupolar splittings have been observed for other glycolipids labeled at this position, only a single delta nu Q was observed. This shows that the orientation of the C2-C3 segment of DTSL relative to the bilayer normal differs from that of other glycolipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931978 TI - Mapping the polarity profiles of general anesthetic target sites using n-alkane (alpha, omega)-diols. AB - The effects of the homologous series of n-alkane-(alpha, omega)-diols have been studied on the inhibition of the purified firefly luciferase enzyme from Photinus pyralis, the inhibition of the purified bacterial luciferase enzyme from Vibrio harveyi, and the induction of general anesthesia in Xenopus laevis tadpoles. All but one of the diols tested were found to be reversible general anesthetics. The diols inhibited firefly luciferase by competing with its normal substrate firefly luciferin, and they inhibited bacterial luciferase by competing with the substrate n-decanal. For all but the smallest agent (1,4-butanediol), only a single diol molecule was found to be involved in the inhibition of the enzymes. Inhibition constants Ki were determined for the enzymes, and general anesthetic EC50 concentrations were determined for tadpoles. These data were then used in conjunction with previously determined n-alkane and n-alcohol data to calculate, as a function of chain length, the incremental standard Gibbs free energies delta (delta G0) for adding apolar -CH2- groups and for converting apolar terminal -CH3 groups to polar -CH2OH groups. The resulting plots of delta (delta G0) versus chain length gave a consistent mapping of the polarity profiles of the anesthetic binding pockets. They clearly reveal the existence of two substantial and distinct polar regions in the anesthetic-binding pocket of firefly luciferase but only one such region for bacterial luciferase and for the unknown target sites underlying general anesthesia. The polarities and geometric properties of these different binding sites for straight-chain anesthetics are discussed in terms of simple models. PMID- 1931979 TI - Response of the headgroup of phosphatidylglycerol to membrane surface charge as studied by deuterium and phosphorus-31 nuclear magnetic resonance. AB - The response to membrane surface charge of the glycerol headgroup of dimyristoyl phosphatidylglycerol (DMPG) was investigated via deuterium and phosphorus-31 nuclear magnetic resonance spectroscopy. The membrane surface charge was manipulated by adding various amounts of neutral dimyristoylphosphatidylcholine (DMPC) and/or positively charged didodecyldimethylammonium bromide (DDAB) to the negatively charged DMPG, selectively deuterated at the alpha and beta segments of its glycerol headgroup. The deuterium and phosphorus-31 nuclear magnetic resonance spectra were all characteristic of random dispersions of liquid crystalline lipids in a bilayer configuration. Differential scanning calorimetry showed that all mixtures investigated exhibited gel to liquid-crystalline phase transitions below 35 degrees C. Measurements of the deuterium quadrupole splitting and of the phosphorus-31 chemical shift anisotropy lead to the following observations. (1) Dilution of the negative surface charge density by the addition of DMPC had little effect on the quadrupole splitting from either alpha- or beta-deuterated DMPG. (2) Direct cancellation of the negative surface charge density by addition of DDAB led to a progressive decrease in the quadrupole splitting measured from alpha-deuterated DMPG, while the quadrupole splitting measured from beta-deuterated DMPG increased. For alpha-deuterated DMPG addition of 0.3 mole fraction of DDAB resulted in the appearance of two distinct quadrupole splittings. No such effect was observed for beta-deuterated DMPG. PMID- 1931980 TI - Structural determination of oligosaccharides derived from lipooligosaccharide of Neisseria gonorrhoeae F62 by chemical, enzymatic, and two-dimensional NMR methods. AB - F62 LOS of Neisseria gonorrhoeae consists of two major LOS components; the higher and smaller molecular weight (MW) components were recognized by MAbs 1-1-M and 3F11 respectively. Base-line separation of the two major oligosaccharide (OS) components from F62 LOS was achieved by Bio-Gel P-4 chromatography after dephosphorylation of the OS mixture. The structures of the two major OSs were studied by chemical, enzymatic, and 2D NMR methods [double quantum filtered COSY (DQF-COSY), delayed COSY (D-COSY), homonuclear Hartmann-Hahn spectroscopy (HOHAHA), pure-absorption 2D NOE NMR] as well as methylation followed by GC/MS analysis. The OS component derived from the MAb 1-1-M defined LOS component was determined to have a V3-(beta-N-acetylgalactosaminyl)neolactotetraose structure (GalNAc is beta 1----3-linked to a neolactotetraose) at one of its nonreducing termini as shown below. The above pentaose is linked to a branched diheptose-KDO core in which a GlcNAc is alpha-linked. The OS component derived from the MAb 3F11 defined LOS component did not have a GalNAc residue. The rest of its structure was identical to that of the OS-1, and a neolactotetraose is exposed at its nonreducing terminus. [formula: see text] PMID- 1931981 TI - Crystallization and preliminary X-ray analysis of the cAMP-dependent protein kinase catalytic subunit from Saccharomyces cerevisiae. AB - A truncated variant of TPK1, the yeast cAMP-dependent protein kinase catalytic subunit, was overexpressed in an engineered strain of Saccharomyces cerevisiae, purified by liquid chromatography, and crystallized from solutions of 2-propanol and magnesium at alkaline pH. The crystals are hexagonal dipyramids, space group P6(1)22 (P6(5)22), with unit-cell parameters a = b = 61 A, c = 320 A. Large single crystals suitable for diffraction analysis are obtainable by microseeding, and diffract beyond 2.8-A resolution. Crystal density measurements reveal 12 kinase monomers per unit cell with a single kinase monomer per asymmetric unit. PMID- 1931982 TI - Enhanced reactivity of a B-Z junction for cleavage by the restriction enzyme MboI. AB - We have been investigating the structure, dynamics, and ligand-binding properties of the interface that exists between a right-handed conformation and a left handed conformation (i.e., a B-Z junction) in synthetic DNA oligomers. Since exo- and endonuclease activity is known to be sensitive to the conformation of the template DNA, we have designed and synthesized a DNA oligonucleotide of 20 base pairs (designated as BZ-III) with an MboI recognition site (GATC) at the location of a potential B-Z junction. The activity of the MboI enzyme toward this molecule and DNA oligomers that contain multiple MboI sites located at B-Z junctions was monitored in the absence and presence of the Z-conformation-inducing reagent cobalt hexaammine. In all cases, the activity of the enzyme was enhanced in the presence of cobalt hexaammine. The activity of MboI toward BZ-III, in the presence and absence of cobalt hexaammine, was also examined when the DNA oligomer is also in the presence of the DNA binding drugs actinomycin D, ametantrone, or ethidium bromide. In all cases, the activity of the enzyme was inhibited in the presence of drug. The results suggest that B-Z junctions are structurally unique and that this uniqueness may alter nuclease activity at sites in or near the junction. PMID- 1931983 TI - Thermodynamic and structural properties of pentamer DNA.DNA, RNA.RNA, and DNA.RNA duplexes of identical sequence. AB - Four pentamers with the general sequence 5'CU(T)GU(T)G/5'CACAG have been prepared by chemical synthesis in order to generate duplex structures with common sequences. The four duplexes studied include the DNA.DNA duplex (5'dCACAG/5'dCTGTG) and the RNA.RNA duplex (5'rCUGUG/5'rCACAG) as well as the two corresponding DNA.RNA heteroduplexes (5'rCUGUG/5'dCACAG and 5'CACAG/5'dCTGTG). The measured entropy, enthalpy, and free energy changes upon melting are reported for each pentamer and compared to the predicted values where possible. Results show that the two DNA.RNA heteroduplexes are destabilized (delta G degrees 25 = 4.2 +/- 0.4 kcal/mol) relative to either the DNA.DNA duplex (delta G degrees 25 = -4.8 +/- 0.5 kcal/mol) or the RNA.RNA duplex (delta G degrees 25 = -5.8 +/- 0.6 kcal/mol). Circular dichroism spectra indicate that the RNA and the two heteroduplexes adopt an A-form conformation, while the DNA conformation is B form. Imino proton NMR spectra also show that the heteroduplex structures resemble the RNA.RNA duplex. PMID- 1931985 TI - The secondary structure in solution of acyl-coenzyme A binding protein from bovine liver using 1H nuclear magnetic resonance spectroscopy. AB - Acyl-coenzyme A binding protein from bovine liver and the protein expressed in Escherichia coli by the recombinant gene of this protein have been studied by two dimensional 1H nuclear magnetic resonance spectroscopy. This protein has, in addition to the ability to bind acyl-coenzyme A, been reported to have several important physiological and biochemical functions. It is known as the diazepam binding inhibitor, as a putative neurotransmitter, as a regulator of insulin release from pancreatic cells, and as a mediator in corticotropin-dependent adrenal steroidogenesis. The only difference between the protein produced by recombinant techniques and the native acyl-coenzyme A binding protein is the N terminal acetyl group present only in the native protein. The two proteins have 86 amino acid residues and a molecular mass of approximately 10,000 Da. Complete assignment of the 1H nuclear magnetic resonances has been obtained for a major proportion of the amino acid residues (55 residues), and partial assignment has been achieved for the others (31 residues). Sequential nuclear Overhauser effects have demonstrated that the protein has a secondary structure consisting of four alpha-helices of residues 1-15, 22-35, 52-60, and 68-85. Furthermore, a large number of long-range nuclear Overhauser effects have been identified, indicating that the assignment given here will provide a basis for a structure determination of this protein in solution by nuclear magnetic resonance spectroscopy. PMID- 1931984 TI - Comparison of binding of mixed ribose-deoxyribose analogues of CUCU to a ribozyme and to GGAGAA by equilibrium dialysis: evidence for ribozyme specific interactions with 2' OH groups. AB - Dissociation constants at 15 degrees C were measured by equilibrium dialysis for the binding of rCrUrCrU, dCrUrCrU, rCdUrCrU, rCrUdCrU, and rCrUrCdU to the L-21 ScaI form of the self-splicing group I LSU intron from Tetrahymena thermophila. Substitution of deoxyribose for ribose in each of the middle two positions makes the free energy change for binding 1-2 kcal/mol less favorable, compared to about 0.3 kcal/mol less favorable for each of the terminal positions. Dissociation constants for binding of the same oligomers to rGGAGAA were measured by optical melting methods. Substitution of a single deoxyribose for ribose makes the free energy change for binding less favorable by 0.4-0.9 kcal/mol for this simple duplex formation. Comparison of the effects for binding to ribozyme and to rGGAGAA indicate that ribozyme-specific tertiary interactions dependent on the middle two 2' OH groups of rCrUrCrU add about 2 kcal/mol of favorable free energy for binding to L-21 ScaI. Comparisons are made with results from gel retardation studies [Pyle, A. M., McSwiggen, J. A., & Cech, T. R. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 8187-8191; Pyle, A. M., & Cech, T. R. (1991) Nature (London) 350, 628-631]. PMID- 1931986 TI - Calorimetric determination of the energetics of the molten globule intermediate in protein folding: apo-alpha-lactalbumin. AB - High-sensitivity differential scanning calorimetry has been used to characterize the energetics of the molten globule state of apo-alpha-lactalbumin. This characterization has been possible by performing temperature scans at different guanidine hydrochloride (GuHCl) concentrations in order to experimentally define the temperature-GuHCl stability surface of the protein. Multidimensional analysis of the heat capacity surface has allowed simultaneous resolution of the energetics of the unfolded and molten globule states. These experiments indicate that the intrinsic enthalpy difference (i.e., excluding additional contributions such as those arising from differential GuHCl binding) between the unfolded and native states is 31.8 kcal/mol at 25 degrees C whereas that of the molten globule and native states is only 7.7 kcal/mol. At the same temperature, the entropy changes are 99.2 and 23.7 cal/K.mol and the heat capacity changes are 1821 and 326 cal/K.mol, respectively. Analysis of the thermodynamic data indicates that in passing from the native to the molten globule state only approximately 19% of the hydrogen bonds are broken. In addition, the magnitude of delta Cp for the molten globule suggests that water does not largely penetrate into the interior of the molten globule, implying that significant hydrophobic interactions are still present in this state. These parameters provide precise energetic constraints to the allowed structural conformations of the molten globule. PMID- 1931987 TI - Pressure effects on carbon monoxide rebinding to the isolated alpha and beta chains of human hemoglobin. AB - The effects of pressure on the recombination kinetics of carbon monoxide binding to the isolated alpha and beta chains of human adult hemoglobin at pH 7, approximately 20 degrees C, were studied by the use of millisecond and nanosecond laser photolyses. The kinetic data were analyzed on the basis of a simple three species model, which assumes two elementary reaction processes of bond formation and ligand migration steps. The activation volume for each elementary step was obtained from the pressure dependence of the rate constants. A pressure-dependent activation volume change from negative to positive values in the bimolecular carbon monoxide association reaction was observed for both of the isolated chains. This finding is attributed to a change of the rate-limiting step from the bond formation step to the ligand migration step. For both of the isolated chains, the activation volumes for ligand migration into and from the protein were estimated as +12-16 and +7-11 cm3 mol-1, respectively. These positive activation volumes for the ligand migration process may be caused by conformational fluctuations of proteins, that is, the conformational changes from "closed" to "open" structure. In the iron-ligand bond formation process, the activation volumes are -15 to -22 cm3 mol-1, which are almost identical to that for the model heme complexes [Taube, D. J., Projahn, H.-D., van Eldik, R., Magde, D., & Traylor, T. G. (1990) J. Am. Chem. Soc. 112, 6880-6886]. Accordingly, the surrounding protein contributions to the activation volumes for the bond formation process could be small.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931988 TI - Identification of signaling states of a sensory receptor by modulation of lifetimes of stimulus-induced conformations: the case of sensory rhodopsin II. AB - Lifetimes of stimulus-induced conformations of the phototaxis receptor sensory rhodopsin II (SR-II) from Halobacterium halobium are modulated with seven receptor analogues. By monitoring the receptor dynamics in vitro and physiological responses of the cell in vivo, we observe receptor signaling efficiency increases with decreasing cycling frequency (turnover number) of the receptor. The results demonstrate that modulating lifetimes of protein conformations at the SR-II photoactivation site with chromophore analogues alters the lifetime of the active conformation at the signaling site. We further explore the relationship between photocycle intermediates and the signaling efficiency by analyzing the time-averaged concentrations of the two long-lived spectral intermediates of the SR-II photocycle: S-II350 and S-II530. The results are consistent with the signaling site being activated during formation of S-II350, but not reset by the transition of S-II350 into S-II530; rather deactivation appears to require subsequent decay of S-II530. The results indicate the structural changes at the photoactivation site in the S-II350----S-II530 transition do not reset the signaling site. The procedure used here, applicable in principle to any photoactivated or ligand-activated receptor, provides an initial approach to identify structural alterations key to the receptor activation process. PMID- 1931989 TI - Rate and mechanism of the assembly of tropomyosin with actin filaments. AB - The rate of assembly of tropomyosin with actin filaments was measured by stopped flow experiments. Binding of tropomyosin to actin filaments was followed by the change of the fluorescence intensity of a (dimethylamino)naphthalene label covalently linked to tropomyosin and by synchrotron radiation X-ray solution scattering. Under the experimental conditions (2 mM MgCl2, 100 mM KCl, pH 7.5, 25 degrees C) and at the protein concentrations used (2.5-24 microM actin, 0.2-3.4 microM tropomyosin) the half-life time of assembly of tropomyosin with actin filaments was found to be less than 1 s. The results were analyzed quantitatively by a model in which tropomyosin initially binds to isolated sites. Further tropomyosin molecules bind contiguously to bound tropomyosin along the actin filaments. Good agreement between the experimental and theoretical time course of assembly was obtained by assuming a fast preequilibrium between free and isolatedly bound tropomyosin. PMID- 1931990 TI - Molecular modeling of the multidomain structures of the proteoglycan binding region and the link protein of cartilage by neutron and synchrotron X-ray scattering. AB - The interaction of proteoglycan monomers with hyaluronate in cartilage is mediated by a globular binding region at the N-terminus of the proteoglycan monomer; this interaction is stabilized by link protein. Sequences show that both the binding region (27% carbohydrate) and the link protein (6% carbohydrate) contain an immunoglobulin (Ig) fold domain and two proteoglycan tandem repeat (PTR) domains. Both proteins were investigated by neutron and synchrotron X-ray solution scattering, in which nonspecific aggregate formation was reduced by the use of citraconylation to modify surface lysine residues. The neutron and X-ray radius of gyration RG of native and citraconylated binding region is 5.1 nm, and the cross-sectional RG (RXS) is 1.9-2.0 nm. No neutron contrast dependence of the RG values was observed; however, a large contrast dependence was seen for the RXS values which is attributed to the high carbohydrate content of the binding region. The neutron RG for citraconylated link protein is 2.9 nm, its RXS is 0.8 nm, and these data are also independent of the neutron contrast. The scattering curves of binding region and link protein were modeled using small spheres. Both protein structures were defined initially by the representation of one domain by a crystal structure for a variable Ig fold and a fixed volume for the two PTR domains calculated from sequence data. The final models showed that the different dimensions and neutron contrast properties of binding region compared to link protein could be attributed to an extended glycosylated C-terminal peptide with extended carbohydrate structures in the binding region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931991 TI - Design of a small peptide-based proteinase inhibitor by modeling the active-site region of barley chymotrypsin inhibitor 2. AB - A synthetic peptide-based proteinase inhibitor was constructed by modeling the regions responsible for inhibition in barley chymotrypsin inhibitor 2 (CI-2). The 18-residue peptide was designed by molecular modeling, based on the crystal structure of CI-2. The amino acid sequences that interact with the proteinase were preserved, as well as residues that maintain the structure of the inhibitory loop. A disulfide bridge was introduced to force the peptide to adopt a cyclic structure. Kinetic studies on binding of the cyclic peptide to subtilisin BPN', subtilisin Carlsberg, chymotrypsin, and pancreatic elastase show that the cyclic peptide retains both the inhibition properties, the kinetic mechanism, and the specificity of the original protein inhibitor. Formation of a cyclic structure was found to be essential, and activity was abolished by reduction of the disulfide. As with CI-2, tightest binding is found to subtilisin BPN', where the Ki value for the cyclic peptide was 28 x 10(-12) M, compared with 29 x 10(-12)M for CI-2 under identical conditions. This remarkable result shows that it is possible to use a short synthetic peptide to model the molecular recognition properties of the intact protein, in this case obtaining full functionality with just 18 residues instead of 83 for CI-2. PMID- 1931992 TI - Inactive and temperature-sensitive folding mutants generated by tryptophan substitutions in the membrane-bound d-lactate dehydrogenase of Escherichia coli. AB - A combination of site-specific mutagenesis and 19F nuclear magnetic resonance has been used to investigate the structural properties of D-lactate dehydrogenase, a membrane-associated enzyme of Escherichia coli. The protein (65,000 Da) has been labeled with 5-fluorotryptophan for 19F nuclear magnetic resonance studies. Tryptophan has been substituted for individual phenylalanine, tyrosine, isoleucine, and leucine residues at various positions throughout the enzyme molecule, and the fluorinated native and substituted tryptophan residues have been used as probes of the local environment. All 24 mutants thus generated are expressed in E. coli. Ten are fully active and purfiable following the usual procedure, while 14 either are inactive or produce low levels of activity. The amount of active enzyme produced from the low-yield mutants is dependent on the temperature at which synthesis is carried out, with more active enzyme produced at 18 degrees C than at 27, 35, or 42 degrees C. Cells grown at 27 degrees C and then incubated at 42 degrees C retain 90-100% of their activity. All of the expressed protein from the inactive mutants is Triton-insoluble, aggregated, and not readily purfiable; the inactive mutant protein appears to be improperly folded. Most of the expressed D-lactate dehydrogenase from the partially active mutants is also Triton-insoluble; a small fraction, however, is soluble in Triton and can be purified to yield active enzyme. All the purified enzymes from these low-yield mutants of D-lactate dehydrogenase have essentially normal VmaxS, and all but two have normal KmS. Once purified, the low-yield mutant enzymes are stable at 42 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931993 TI - Structural determinants within residues 180-199 of the rodent alpha 5 nicotinic acetylcholine receptor subunit involved in alpha-bungarotoxin binding. AB - Synthetic peptides corresponding to sequence segments of the nicotinic acetylcholine receptor (nAChR) alpha subunits have been used to identify regions that contribute to formation of the binding sites for cholinergic ligands. We have previously defined alpha-bungarotoxin (alpha-BTX) binding sequences between residues 180 and 199 of a putative rat neuronal nAChR alpha subunit, designated alpha 5 [McLane, K. E., Wu, X., & Conti-Tronconi, B. M. (1990) J. Biol. Chem. 265, 9816-9824], and between residues 181 and 200 of the chick neuronal alpha 7 and alpha 8 subunits [McLane, K. E., Wu, X., Schoepfer, R., Lindstrom, J., & Conti-Tronconi, B. M. (1991) J. Biol. Chem. (in press)]. These sequences are relatively divergent compared with the Torpedo and muscle nAChR alpha 1 alpha-BTX binding sites, which indicates a serious limitation of predicting functional domains of proteins based on homology in general. Given the highly divergent nature of the alpha 5 sequence, we were interested in determining the critical amino acid residues for alpha-BTX binding. In the present study, the effects of single amino acid substitutions of Gly or Ala for each residue of the rat alpha 5(180-199) sequence were tested, using a competition assay, in which peptides compete for 125I-alpha-BTX binding with native Torpedo nAChR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931994 TI - Interaction of cholesterol with synthetic sphingomyelin derivatives in mixed monolayers. AB - To study the structural requirements of the molecular interactions between cholesterol and sphingomyelins in model membranes, sphingomyelin derivatives were synthesized in which (a) the 3-hydroxy group was replaced with a hydrogen atom or with a methoxy, ethoxy, or tetrahydropyranyloxy group, (b) the N-acyl chain length was varied, and (c) the N-acyl chain length contained an alpha-hydroxy group. The chemical syntheses of these derivatives from DL-erythro-sphingosine are reported. The properties of these sphingomyelin derivatives were examined in monolayer membranes at the air/water interface. The mean molecular area of the pure N-stearoylsphingomyelin derivatives was determined, and the effects of cholesterol on the condensation of sphingomyelin packing in the monolayer were recorded. It was observed that replacement of the 3-hydroxy group of sphingomyelin with a hydrogen atom or its substitution with a methoxy or ethoxy group did not affect the ability of cholesterol to condense the molecular packing in monolayers. Even when a bulky tetrahydropyranyloxy group was introduced at the 3-hydroxy position of egg sphingomyelin, cholesterol was still able to condense the molecular packing of this derivative. The condensing effect of cholesterol on derivatives of N-stearoyl-SPMs was significantly larger than the comparable effect observed with 1,2-distearoyl-sn-glycero-3-phosphocholine or 1,2 dipalmitoyl-sn-glycero-3-phosphocholine. Our results with 3-hydroxysphingomyelins having differing N-acyl chain lengths (i.e., N-stearoyl, N-myristoyl, and N lauroyl), and with 3-hydroxy-N-(alpha-hydroxypalmitoyl)sphingomyelin also indicated that cholesterol was able to induce condensation of the molecular packing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931995 TI - Spiropentaneacetic acid as a specific inhibitor of medium-chain acyl-CoA dehydrogenase. AB - To study the structure-activity relationship between pentanoic acid analogues and the inhibition of fatty acid oxidation, a number of 4-pentenoic and methylenecyclopropaneacetic acid derivatives were prepared. All compounds inhibited palmitoylcarnitine oxidation in rat liver mitochondria, with 50% inhibition occurring at a concentration between 6 and 100 microM. However, only methylenecyclopropaneacetic acid (MCPA) and spiropentaneacetic acid (SPA) showed in vivo inhibitory activity in rats as indicated by the occurrence of dicarboxylic aciduria. Rats treated with SPA excreted metabolites derived only from fatty acid oxidation whereas MCPA-treated rats also excreted metabolites derived from branch-chained amino acid and lysine metabolism. SPA is a specific inhibitor of fatty acid oxidation without affecting amino acid metabolism. The site of inhibition is medium-chain acyl-CoA dehydrogenase (MCAD). In contrast, MCPA inhibited both MCAD and short-chain acyl-CoA dehydrogenase with a stronger inhibition toward the latter. The inhibition of fatty acid oxidation by both inhibitors was partially reversible by glycine or l-carnitine. Since SPA does not form a ring-opened nucleophile such as that proposed for MCPA in the inhibition of FAD prosthetic group in acyl-CoA dehydrogenases, we propose that the irreversible inhibition by SPA occurs by a tight complex without forming a covalent bond to the isoalloxazine ring in FAD. PMID- 1931996 TI - Multibilayer structure of dimyristoylphosphatidylcholine dihydrate as determined by energy minimization. AB - Complete energy minimization was carried out on the multibilayer crystal structure of 1,2-dimyristoyl-sn-glycero-3-phosphocholine dihydrate (DMPC.2H2O), starting from the X-ray structure determination reported by Pearson and Pascher (1979) Nature 281, 499-501. The asymmetric unit contains two nonidentical DMPC molecules and four water molecules. Minimization removed the acyl chain disorder present in the X-ray structure and caused the carbon planes of the acyl chains to become mutually parallel. Two energy-minimized structures (structures I and II) were found which mainly differed in the hydrogen-bonding arrangement of the waters of hydration. In structure I as in the X-ray structure, one of the water molecules forms a hydrogen-bonded bridge between successive bilayers; but in structure II, all hydrogen bonds are satisfied on the same bilayer. Structure II corresponds to the global energy minimum and is also a suitable structure for single bilayers. The lattice constants and cell volume of the minimized structures are close to the experimental values. The electrostatic force between DMPC bilayers is attractive. The mean hydration energy of the water is -14.2 kcal/mol, which is 2.5 kcal/mol lower than the binding energy of ice. PMID- 1931997 TI - A leucine to proline mutation at position 233 in the insulin receptor inhibits cleavage of the proreceptor and transport to the cell surface. AB - We have previously shown that a homozygous mutation encoding a substitution of proline for leucine at position 233 in the insulin receptor is linked with the syndrome of leprechaunism, being a lethal form of insulin resistance in newborn children. Specific binding of insulin and insulin-stimulated autophosphorylation of the insulin receptor are nearly absent in fibroblasts from the leprechaun patient. To examine the molecular basis of the observed insulin receptor abnormalities, CHO cell lines overexpressing mutant insulin receptors were made by transfection. The results show that the mutation inhibits cleavage and transport of the proreceptor from intracellular sites to the cell surface. As the mutant receptor is poorly precipitated by two different monoclonal antibodies recognizing epitopes on undenatured wild-type alpha-subunits, the mutation probably affects overall folding of the alpha-subunit. The mutant proreceptor is unable to bind insulin and exhibits no insulin-stimulated autophosphorylation. These data explain the abnormalities seen in the patient's fibroblasts. Pulse chase labeling experiments on transfected cells show that the mutant precursor has an extended half-life (approximately 5 h) compared to the precursor of wild type insulin receptors (approximately 2 h). This mutation is the first example of a naturally occurring mutation in the insulin receptor which completely blocks cleavage of the proreceptor and transport to the cell surface. PMID- 1931998 TI - Transition-state analysis of nucleoside hydrolase from Crithidia fasciculata. AB - The transition state of nucleoside hydrolase from the trypanosome Crithidia fasciculata has been characterized by multiple Vmax/Km kinetic isotope effects with labeled inosine and adenosine as substrates. Nucleoside hydrolase catalyzes the hydrolysis of the N-glycosidic linkage of the commonly occurring purine and pyrimidine nucleosides, with Vmax/Km ranging over 2 orders of magnitude. The kinetic isotope effects for inosine were [1'-3H] = 1.150 +/- 0.006, [2'-3H] = 1.161 +/- 0.003, [1'-14C] = 1.044 +/- 0.004, [9-15N] = 1.026 +/- 0.004, [4'-3H] = 0.992 +/- 0.003, and [5'-3H] = 1.051 +/- 0.003. The magnitude of the kinetic isotope effects for inosine, an equivalent [1'-3H] kinetic isotope effect for the poor substrate adenosine, and the rapid equilibrium random kinetic mechanism [Parkin D, W., Horenstein, B. A., Abdulah, D. R., Estupinan, B., & Schramm, V. L. (1991) J. Biol. Chem. (in press)] all indicate that the isotope effects are fully expressed. The kinetic and solvent deuterium isotope effects have been used to analyze the transition-state structure using bond energy bond order vibrational analysis. The transition state involves a protonated hypoxanthine leaving group with a C-N glycosidic bond elongated to approximately 2 A. The ribose group contains substantial carbocationic character, unusually strong hyperconjugation of H2', and a bond length of approximately 3 A to the incoming oxygen nucleophile. The remote isotope effect (4'-3H and 5'-3H) and the results of transition-state calculations provide the most detailed description of the steric and bonding properties of an enzyme-stabilized transition state. PMID- 1932000 TI - Substrate binding to chloramphenicol acetyltransferase: evidence for negative cooperativity from equilibrium and kinetic constants for binary and ternary complexes. AB - Chloramphenicol acetyltransferase (CAT) catalyzes the acetyl-CoA-dependent acetylation of chloramphenicol by a ternary complex mechanism with a rapid equilibrium and essentially random order of addition of substrates. Such a kinetic mechanism for a two-substrate reaction provides an opportunity to compare the affinity of enzyme for each substrate in the binary complexes (1/Kd) with corresponding values (1/Km) for affinities in the ternary complex where any effect of the other substrate should be manifest. The pursuit of such information for CAT involved the use of four independent methods to determine the dissociation constant (Kd) for chloramphenicol in the binary complex, techniques which included stopped-flow measurements of on and off rates, and a novel fluorometric titration method. The binary complex dissociation constant (Kd) for acetyl-CoA was measured by fluorescence enhancement and steady-state kinetic analysis. The ternary complex dissociation constant (Km) for each substrate (in the presence of the other) was determined by kinetic and fluorometric methods, using CoA or ethyl-CoA to form nonproductive ternary complexes. The results demonstrate an unequivocal decrease in affinity of CAT for each of its substrates on progression from the binary to the ternary complex, a phenomenon most economically described as negative cooperativity. The binary complex dissociation constants (Kd) for chloramphenicol and acetyl-CoA are 4 microM and 30 microM whereas the corresponding dissociation constants in the ternary complex (Km) are 12 microM and 90 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1931999 TI - Intrinsic fluorescence of chloramphenicol acetyltransferase: responses to ligand binding and assignment of the contributions of tryptophan residues by site directed mutagenesis. AB - Replacement by tyrosine or phenylalanine was used to assign the additive contributions of each of the three tryptophan residues of chloramphenicol acetyltransferase (CAT) to its intrinsic fluorescence on excitation at 295 nm. During the assessment of the fluorescence responses of the wild-type enzyme to the binding of ligands, it was found that the overlapping absorption spectra of chloramphenicol and tryptophan, with an attendant inner filter effect, required the use of a displacement technique involving an alternative substrate (the p cyano analogue of chloramphenicol) without significant absorption at 295 nm. By the use of two-Trp, one-Trp, and Trp-less variants, in combination with this displacement technique, it was possible to demonstrate that Trp-86 and Trp-152 are involved in the fluorescence quenching associated with the binding of chloramphenicol, most likely via nonradiative energy transfer from these residues to the bound substrate. Trp-152 is mainly responsible for the fluorescence enhancement accompanying the binding of acetyl-CoA (and CoA) through proximity effects and solvent exclusion on substrate association. PMID- 1932001 TI - Identification of an inhibitor of microtubule assembly present in juvenile brain which displays a novel mechanism of action involving suppression of self nucleation. AB - An inhibitor of microtubule assembly has been identified and partially purified from microtubule-depleted brain extracts from day-old chicks and 4-month-old calf. This inhibitor suppresses the self-nucleation of microtubules in vitro with minimal effect upon the final extent of assembly. It may have a developmental role in vivo as it is not detected in adult brain from either cattle or rabbit. PMID- 1932002 TI - Initiation of the extrinsic pathway of blood coagulation: evidence for the tissue factor dependent autoactivation of human coagulation factor VII. AB - Previous studies demonstrated proteolytic activation of human blood coagulation factor VII by an unidentified protease following complex formation with tissue factor expressed on the surface of a human bladder carcinoma cell line (J82). In the present study, an active-site mutant human factor VII cDNA (Ser344----Ala) has been constructed, subcloned, and expressed in baby hamster kidney cells. Mutant factor VII was purified to homogeneity in a single step from serum-free culture supernatants by immunoaffinity column chromatography. Mutant factor VII was fully carboxylated, possessed no apparent clotting activity, and was indistinguishable from plasma factor VII by SDS-PAGE. Cell binding studies indicated that mutant factor VII bound to J82 tissue factor with essentially the same affinity as plasma factor VII and was cleaved by factor Xa at the same rate as plasma factor VII. In contrast to radiolabeled single-chain plasma factor VII that was progressively converted to two-chain factor VIIa on J82 monolayers, mutant factor VII was not cleaved following complex formation with J82 tissue factor. Incubation of radiolabeled mutant factor VII with J82 cells in the presence of recombinant factor VIIa resulted in the time-dependent and tissue factor dependent conversion of single-chain mutant factor VII to two-chain mutant factor VIIa. Plasma levels of antithrombin III had no discernible effect on the factor VIIa catalyzed activation of factor VII on J82 cell-surface tissue factor but completely blocked this reaction catalyzed by factor Xa. These results are consistent with an autocatalytic mechanism of factor VII activation following complex formation with cell-surface tissue factor, which may play an important role in the initiation of extrinsic coagulation in normal hemostasis. PMID- 1932003 TI - Expression and initial characterization of five site-directed mutants of the N terminal half-molecule of human transferrin. AB - Five site-directed mutants of the N-terminal half-molecule of human serum transferrin have been expressed in baby hamster kidney cells and purified to homogeneity. Expression levels and overall yields varied considerably from the wild-type protein, depending on the mutant in question. The mutants are D63S, D63C, G65R, K206Q, and H207E and are based on mutations observed in a variety of transferrins of known sequence. Their molecular masses, determined by electrospray mass spectrometry, agree with theory, except for the D63C mutant, which appears to be cysteinylated. All mutants bind iron but with varying affinities; qualitatively, in increasing order D63S approximately D63C approximately G65R much less than wild type less than or equal to H207E much less than K206Q. In general, reduction of formal negative charge within the binding cleft shifts the visible spectral maximum of the iron complex toward the blue and reduces the affinity for iron, and increasing the formal negative charge shifts the visible maximum toward the red and increases the affinity for iron. The K206Q mutant is exceptional inasmuch as its visible maximum shows a blue shift, but its affinity for iron is the greatest of all of the mutants studied. All mutants reported, in addition to the wild-type protein, exhibit very similar visible molar extinction coefficients for the iron complex and very similar changes in extinction coefficients at 240 nm on binding Fe(III) or Ga(III). These results suggest that in all cases the bound metal ion is coordinated by two tyrosyl side chains. PMID- 1932004 TI - Differences in the binding mechanism of RU486 and progesterone to the progesterone receptor. AB - The binding mechanism of the antagonist RU486 to the progesterone receptor was compared with that of the agonists progesterone and R5020. Both progesterone and RU486 bound to the receptor with a Hill coefficient of 1.2, indicating the binding of each ligand is positive cooperative. However, when each ligand was used to compete with [3H]progesterone for binding to the receptor at receptor concentrations near 8 nM, at which the receptor is likely a dimer, the competition curve for RU486 was significantly steeper than the curves for progesterone and R5020 (p less than 0.001). This indicated that a difference in the binding mechanism of RU486 and progesterone can be detected when both ligands are present. In contrast, at receptor concentrations near 1 nM, at which the receptor is likely a monomer, the competition curves for all three ligands were indistinguishable (p = 0.915). These results indicate that RU486 and agonists have different binding mechanisms for the receptor and further suggest that this difference may be related to site-site interactions within the receptor. PMID- 1932005 TI - Selecting high-affinity binding proteins by monovalent phage display. AB - Variants of human growth hormone (hGH) with increased affinity and specificity for the hGH receptor were isolated using an improved phage display system. Nearly one million random mutants of hGH were generated at 12 sites previously shown to modulate binding to the hGH receptor or human prolactin (hPRL) receptor. The mutant hormones were displayed in a monovalent fashion from filamentous phage particles as fusions to the gene III product of M13 packaged within each particle. After three to six cycles of enrichment for hGH-phage particles that bound to hGH receptor beads, we isolated hGH mutants that exhibited consensus binding sequences for the hGH receptor. Residues previously identified as important for hGH receptor binding by alanine-scanning mutagenesis were more highly conserved by this selection method. However, other residues nearby were not optimal, and by mutating them, hormone variants having greater affinity and selectivity for the hGH receptor were isolated. This approach should be useful for those who wish to modify and understand the energetics of protein-ligand interfaces. PMID- 1932007 TI - Energetics of 3-oxo-delta 5-steroid isomerase: source of the catalytic power of the enzyme. AB - Knowledge of the partitioning of the putative dienol intermediate (2) by steroid isomerase (KSI) (Hawkinson et al. 1991), in conjunction with various steady-state kinetic parameters, allows elucidation of the detailed free energy profile for the KSI-catalyzed conversion of 5-androstene-3,17-dione (1) to 4-androstene-3,17 dione (3). This free energy profile shows four kinetically significant energy barriers (substrate binding, the two chemical steps, and dissociation of product) that must be traversed upon conversion of 1 to 3. Thus, no single step of the catalytic cycle is cleanly rate-limiting. The source of the catalytic power of KSI is discussed via comparison of the free energy profile for the KSI-catalyzed isomerization with those for the acetate-catalyzed isomerization and the aqueous reaction at pH 7. Similarities between the energetics of the KSI-catalyzed and triosephosphate isomerase catalyzed reactions are also noted. PMID- 1932006 TI - Marked effects of salt on estrogen receptor binding to DNA: biologically relevant discrimination between DNA sequences. AB - Avidin-biotin complexed with DNA (ABCD) assays were employed to determine the binding affinity of estrogen receptor (ER) to DNA under various salt conditions. Type and concentration of salt in the reaction buffer dramatically affected the ability of the ER to discriminate between DNA sequences. Under appropriate salt conditions, ER was able to bind to the estrogen response element from the Xenopus vitellogenin A2 gene with at least 3 orders of magnitude greater affinity than a two base pair mutant sequence, and 5 orders of magnitude greater affinity than plasmid DNA. In these studies, the best discrimination was observed under conditions of salt type and concentration that more closely approximated intracellular conditions, i.e., 100-150 mM potassium salts. Analysis of the binding affinities for ER to all three types of DNA over a range of KCl concentrations indicated that the ionic interactions upon ER binding were the same for the three DNA molecules tested. Therefore, the additional stability of ER binding to target DNA sequences was contributed by nonionic interactions. PMID- 1932008 TI - Studies of the catalytic mechanism of an active-site mutant (Y14F) of delta 5-3 ketosteroid isomerase by kinetic deuterium isotope effects. AB - delta 5-3-Ketosteroid isomerase (EC 5.3.3.1) from Pseudomonas testosteroni catalyzes the conversion of androst-5-ene-3,17-dione to androst-4-ene-3,17-dione by a stereoselective transfer of the 4 beta-proton to the 6 beta-position. The rate-limiting step has been shown to be the concerted enolization of the enzyme bound substrate comprising protonation of the 3-carbonyl oxygen by Tyr-14 and abstraction of the 4 beta-proton by Asp-38 [Xue, L., Talalay, P., & Mildvan, A. S. (1990) Biochemistry 29, 7491-7500]. Primary, secondary, solvent, and combined kinetic deuterium isotope effects have been used to investigate the mechanism of the Y14F mutant, which lacks the proton donor and is 10(4.7)-fold less active catalytically than the wild-type enzyme. With [4 beta-D]androst-5-ene-3,17-dione as a substrate in H2O, a lag in product formation is observed which approaches, by a first-order process, the rate observed with protonated substrate. With the protonated substrate in D2O, a burst in product formation is detected by derivative analysis of the kinetic data which approaches the rate observed with the 4 beta-deuterated substrate in D2O. The absence of such lags or bursts with the protonated substrate in H2O or with the 4 beta-deuterated substrate in D2O, as well as the detection of buffer catalysis by phosphate at pH 6.8, indicates that one or more intermediates dissociate from the enzyme and partition to substrate 31.6 times faster than to product.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932009 TI - Conformational flexibility of aqueous monomeric and dimeric insulin: a molecular dynamics study. AB - A series of molecular dynamics simulations have been used to investigate the nature of monomeric and dimeric insulin in aqueous solution. It is shown that in the absence of crystal contacts both monomeric and dimeric insulin have a high degree of intrinsic flexibility. Neither of the two monomer conformations of 2Zn crystalline insulin appears to be favored in solution nor is the asymmetry of the crystal dimer reduced in the absence of crystal contacts. A shift is observed in the relative positions of molecules 1 and 2 in the dimer compared with that found in the crystal, which may have consequences for the prediction of the effects of mutants in the monomer-monomer interface designed to alter the self-association properties of insulin. PMID- 1932010 TI - NMR study of the phosphate-binding elements of Escherichia coli elongation factor Tu catalytic domain. AB - The phosphoryl-binding elements in the GDP-binding domain of elongation factor Tu were studied by heteronuclear proton observe methods. Five proton resonances were found below 10.5 ppm. Two of these were assigned to the amide groups of Lys 24 and Gly 83. These are conserved residues in each of the consensus sequences. Their uncharacteristic downfield proton shifts are attributed to strong hydrogen bonds to phosphate oxygens as for resonances in N-ras-p21 [Redfield, A. G., & Papastavros, M. Z. (1990) Biochemistry 29, 3509-3514]. The Lys 24 of the EF-Tu G domain has nearly the same proton and nitrogen shifts as the corresponding Lys 16 in p21. These results suggest that this conserved lysine has a similar structural role in proteins in this class. The tentative Gly 83 resonance has no spectral analogue in p21. A mutant protein with His 84 changed to glycine was fully 15N labeled and the proton resonance assigned to Gly 83 shifted downfield by 0.3 ppm, thereby supporting the assignment. PMID- 1932011 TI - Detection of conformational changes in actin by fluorescence resonance energy transfer between tyrosine-69 and cysteine-374. AB - The distance between 5-(dimethylamino)naphthalene-1-sulfonyl chloride (dansyl chloride or DNS-Cl) attached to Tyr-69 and N-[[4-[4 (dimethylamino)phenyl]azo]phenyl]maleimide (DABMI) or N-[4-(dimethylamino)-3,5 dinitrophenyl]maleimide (DDPM) attached to Cys-374 in an actin monomer was measured to be 2.51 nm or 2.27 +/- 0.04 nm, respectively, by fluorescence resonance energy transfer. This distance does not change significantly when the actin monomer binds DNase I, when the monomer is polymerized, when the polymer interacts with myosin subfragment 1, or when it interacts with tropomyosin troponin in the presence and absence of Ca2+. Changes in the distance were within 0.1 nm. The results indicate that the structure of the region involving Tyr-69 and Cys-374 is substantially rigid. A large blue shift (about 15 nm) of the fluorescence spectrum and a large increase (about 80%) in the fluorescence intensity of DNS-actin were observed when DNS-actin was denatured upon addition of EDTA. On the other hand, a red shift (about 7 nm) of the fluorescence spectrum and a large decrease (about 50%) in the fluorescence intensity were observed when DNS-actin was completely unfolded in 8 M urea. The results indicate that dansyl chromophore becomes less exposed to the aqueous environment by EDTA denaturation in contradiction to the case of intrinsic tryptophan residues in G-actin. Resonance energy transfer measurements showed that the distance between probes attached to Tyr-69 and Cys-374 on an actin monomer changes by 0.37 nm during EDTA denaturation, but that the distance becomes longer than 4.0 nm in 8 M urea in which no energy transfer is observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932012 TI - Determinants of protein hyperthermostability: purification and amino acid sequence of rubredoxin from the hyperthermophilic archaebacterium Pyrococcus furiosus and secondary structure of the zinc adduct by NMR. AB - The purification, amino acid sequence, and two-dimensional 1H NMR results are reported for the rubredoxin (Rd) from the hyperthermophilic archaebacterium Pyrococcus furiosus, an organism that grows optimally at 100 degrees C. The molecular mass (5397 Da), iron content (1.2 +/- 0.2 g-atom of Fe/mol), UV-vis spectrophotometric properties, and amino acid sequence (60% sequence identity with Clostridium pasteurianum Rd) are found to be typical of this class of redox protein. However, P. furiosus Rd is remarkably thermostable, being unaffected after incubation for 24 h at 95 degrees C. One- and two-dimensional 1H nuclear magnetic resonance spectra of the oxidized [Fe(III)Rd] and reduced [Fe(II)Rd] forms of P. furiosus Rd exhibited substantial paramagnetic line broadening, and this precluded detailed 3D structural studies. The apoprotein was not readily amenable to NMR studies due to apparent protein oxidation involving the free cysteine sulfhydryls. However, high-quality NMR spectra were obtained for the Zn substituted protein, Zn(Rd), enabling detailed NMR signal assignment for all backbone amide and alpha and most side-chain protons. Secondary structural elements were determined from qualitative analysis of 2D Overhauser effect spectra. Residues A1-K6, Y10-E14, and F48-E51 form a three-strand antiparallel beta-sheet, which comprises ca. 30% of the primary sequence. Residues C5-Y10 and C38-A43 form types I and II amide-sulfur tight turns common to iron-sulfur proteins. These structural elements are similar to those observed by X-ray crystallography for native Rd from the mesophile C. pasteurianum. However, the beta-sheet domain in P. furiosus Rd is larger than that in C. pasteurianum Rd and appears to begin at the N-terminal residue. From analysis of the secondary structure, potentially stabilizing electrostatic interactions involving the charged groups of residues Ala(1), Glu(14), and Glu(52) are proposed. These interactions, which are not present in rubredoxins from mesophilic organisms, may prevent the beta-sheet from "unzipping" at elevated temperatures. PMID- 1932014 TI - Resonance Raman spectra of plastocyanin and pseudoazurin: evidence for conserved cysteine ligand conformations in cupredoxins (blue copper proteins). AB - New resonance Raman (RR) spectra at 15 K are reported for poplar (Populus nigra) and oleander (Oleander nerium) plastocyanins and for Alcaligenes faecalis pseudoazurin. The spectra are compared with those of other blue copper proteins (cupredoxins). In all cases, nine or more vibrational modes between 330 and 460 cm-1 can be assigned to a coupling of the Cu-S(Cys) stretch with Cys ligand deformations. The fact that these vibrations occur at a relatively constant set of frequencies is testimony to the highly conserved ground-state structure of the Cu-Cys moiety. Shifts of the vibrational modes by 1-3 cm-1 upon deuterium exchange can be correlated with N-H...S hydrogen bonds from the protein backbone to the sulfur of the Cys ligand. There is marked variability in the intensities of these Cys-related vibrations, such that each class of cupredoxin has its own pattern of RR intensities. For example, plastocyanins from poplar, oleander, French bean, and spinach have their most intense feature at approximately 425 cm 1; azurins show greatest intensity at approximately 410 cm-1, stellacyanin and ascorbate oxidase at approximately 385 cm-1, and nitrite reductase at approximately 360 cm-1. These variable intensity patterns are related to differences in the electronic excited-state structures. We propose that they have a basis in the protein environment of the copper-cysteinate chromophore. A further insight into the vibrational spectra is provided by the structures of the six cupredoxins for which crystallographic refinements at high resolution are available (plastocyanins from P. nigra, O. nerium, and Enteromorpha prolifera, pseudoazurin from A. faecalis, azurin from Alcaligenes denitrificans, and cucumber basic blue protein). The average of the Cu-S(Cys) bond lengths is 2.12 +/- 0.05 A. Since the observed range of bond lengths falls within the precision of the determinations, this variation is considered insignificant. The Cys ligand dihedral angles are also highly conserved. Cu-S gamma-C beta-C alpha is always near -170 degrees and S gamma-C beta-C alpha-N near 170 degrees. As a result, the Cu-S gamma bond is coplanar with the Cys side-chain atoms and part of the polypeptide backbone. The coplanarity accounts for the extensive coupling of Cu-S stretching and Cys deformation modes as seen in the RR spectrum. The conservation of this copper-cysteinate conformation in cupredoxins may indicate a favored pathway for electron transfer. PMID- 1932013 TI - Construction of a synthetic gene for an R-plasmid-encoded dihydrofolate reductase and studies on the role of the N-terminus in the protein. AB - R67 dihydrofolate reductase (DHFR) is a novel protein that provides clinical resistance to the antibacterial drug trimethoprim. The crystal structure of a dimeric form of R67 DHFR indicates the first 16 amino acids are disordered [Matthews et al. (1986) Biochemistry 25, 4194-4204]. To investigate whether these amino acids are necessary for protein function, the first 16 N-terminal residues have been cleaved off by chymotrypsin. The truncated protein is fully active with kcat = 1.3 s-1, Km(NADPH) = 3.0 microM, and Km(dihydrofolate) = 5.8 microM. This result suggests the functional core of the protein resides in the beta-barrel structure defined by residues 27-78. To study this protein further, synthetic genes coding for full-length and truncated R67 DHFRs were constructed. Surprisingly, the gene coding for truncated R67 DHFR does not produce protein in vivo or confer trimethoprim resistance upon Escherichia coli. Therefore, the relative stabilities of native and truncated R67 DHFR were investigated by equilibrium unfolding studies. Unfolding of dimeric native R67 DHFR is protein concentration dependent and can be described by a two-state model involving native dimer and unfolded monomer. Using absorbance, fluorescence, and circular dichroism techniques, an average delta GH2O of 13.9 kcal mol-1 is found for native R67 DHFR. In contrast, an average delta GH2O of 11.3 kcal mol-1 is observed for truncated R67 DHFR. These results indicate native R67 DHFR is 2.6 kcal mol-1 more stable than truncated protein. This stability difference may be part of the reason why protein from the truncated gene is not found in vivo in E. coli. PMID- 1932015 TI - An isotope edited classical Raman difference spectroscopic study of the interactions of guanine nucleotides with elongation factor Tu and H-ras p21. AB - We have measured the Raman spectrum of GDP bound to the elongation factor protein, EF-Tu, and the c-Harvey-ras protein, p21, two proteins of the guanine nucleotide binding family. In order to separate the Raman spectrum of the nucleotide from the much more intense protein spectrum, we investigate the feasibility of "tagging" the normal modes of the nucleotide by isotopic substitution, here by incoporating deuterium-labeled guanine at the C8 position into the active site. A difference spectrum between the labeled and unlabeled protein-nucleotide complex shows the changes in the Raman spectrum of the bound nucleotide that arise from the isotopic exchange. We find that surprisingly good Raman spectra of bound ligands can be obtained with this method and that the method can be easily generalized to other systems. The data show that the guanine amino group of the nucleotide interacts differently with both EF-Tu and p21 than it does with water, showing a change in hydrogen-bonding properties upon binding. On the other hand, no change in hydrogen bonding is observed at guanine's N7. The data strongly suggest that the conformation of the nucleotide when bound to EF-Tu and that p21 is the C2' endo pucker of the ribose ring and anti about the glycosidic bond. These results are compared to previous structural and chemical studies. PMID- 1932016 TI - RNA folding during transcription by T7 RNA polymerase analyzed using the self cleaving transcript assay. AB - We have used a self-cleaving RNA molecule (a "hammerhead") to study the length dependent folding of RNA produced during transcription by T7 RNA polymerase. Transcript elongation is arrested at defined positions using chain-terminating ribonucleoside triphosphate analogues, 3'-deoxynucleoside triphosphates. When the nascent transcript attains the minimum length required for the "hammerhead" domain of the transcript to fully emerge from the ternary complex, the "hammerhead" structure forms and self-cleaves, producing a truncated product. The experiment yields an RNA sequencing ladder which terminates at the length at which cleavage becomes possible; the sequencing ladder is compared to that generated by using a noncleaving control template. We have shown that 13 nucleotides past the cleavage point must be synthesized before the transcript can self-cleave in the ternary complex whereas RNA freed from the complex by heating can cleave with only 3 or more nucleotides present beyond the cleavage site. The results indicate that the RNA in T7 RNA polymerase is not free of steric interactions in the ternary complex and not available for structure formation until it is at least 10 bases away from the site of polymerization. The results suggest that the maximum possible length of the RNA-DNA hybrid in the ternary complexes is 10. The relevance of the results in comparisons with other RNA polymerases, especially Escherichia coli RNA polymerase, is discussed. PMID- 1932017 TI - Inhibition of the B to Z transition in poly(dGdC).poly(dGdC) by covalent attachment of ethidium: equilibrium studies. AB - The effects of covalent modification of poly(dGdC).poly(dGdC) and poly(dGm5dC).poly(dGm5dC) by ethidium monoazide (a photoreactive analogue of ethidium) on the salt-induced B to Z transition are examined. Earlier studies have shown ethidium monoazide to bind DNA (in the absence of light) in a manner identical to that of the parent ethidium bromide. Photolysis of the ethidium monoazide-DNA complex with visible light results in the covalent attachment of the photoreactive analogue to the DNA. This ability to form a covalent adduct was utilized to probe the effects of an intercalating irreversibly bound adduct on the salt-induced B to Z transition of the poly(dGdC).poly(dGdC) and poly(dGm5dC).poly(dGm5dC) polynucleotides. In the absence of drug, the salt induced transition from the B to Z structure occurs in a highly cooperative manner. In contrast, this cooperativity is diminished as the concentration of covalently attached drug is increased. The degree of inhibition of the B to Z transition is quantitated as a function of the concentration of covalently attached drug. At a concentration of one drug bound per four base pairs for poly(dGdC).poly(dGdC) and seven base pairs for poly(dGm5dC).poly(dGm5dC), total inhibition of this transition is achieved. Lower concentrations of bound drug were effective in the partial inhibition of this transition. The effects of the covalently bound intercalator on the energetics of the B to Z transition were determined and demonstrated that the adduct is effective in locking the alternating copolymer in a right-handed conformation under high salt conditions. PMID- 1932018 TI - Inhibition of the B to Z transition in poly(dGdC).poly(dGdC) by covalent attachment of ethidium: kinetic studies. AB - The photoaffinity analogue ethidium monoazide was used to prepare samples of poly(dGdC).poly(dGdC) containing covalently attached ethidium. The effects of both noncovalently and covalently bound ethidium on the kinetics of the NaCl induced B to Z transition in poly(dGdC).poly(dGdC) was examined using absorbance and fluorescence spectroscopy to monitor the reaction. Covalently and noncovalently attached ethidium were equal in the extent to which they reduce the rate of the B to Z transition. By using fluorescence to selectively monitor the fate of noncovalently bound ethidium over the course of the transition, we found that ethidium completely dissociates as the reaction proceeds, but at a rate that lags behind the conversion of the polymer to the Z form. These experiments provide evidence for the redistribution of noncovalently bound ethidium over the course of the B to Z transition, leading to the development of biphasic reaction kinetics. The observed kinetics suggest that the primary effect of both covalently and noncovalently bound ethidium is on the nucleation step of the B to Z transition. The reduction in the rate of the B to Z transition by noncovalently or covalently bound ethidium may be quantitatively explained as resulting from the reduced probability of finding a drug-free length of helix long enough for nucleation to occur. As necessary ancillary experiments, the defined length deoxyoligonucleotides (dGdC)4, (dGdC)5, and (dGdC)6 were synthesized and used in kinetic experiments designed to determine the nucleation length of the B to Z transition, which was found to be 6 bp. The activation energy of the B to Z transition was demonstrated to be independent of the amount of covalently bound ethidium and was found to be 21.2 +/- 1.1 kcal mol-1. Covalent attachment of ethidium was observed to increase the rate of the reverse Z to B transition, presumably by locking regions of the polymer into a right-handed conformation and thereby providing nucleation sites from which the Z to B conversion may propagate. PMID- 1932019 TI - Effect of head-group structure and counterion condensation on phase equilibria in anionic phospholipid-water systems studied by 2H, 23Na, and 31P NMR and X-ray diffraction. AB - The phase equilibria, hydration, and sodium counterion association for the systems DOPA-2H2O, DOPS-2H2O, DOPG-2H2O, and DPG-2H2O were investigated with 2H, 23Na, and 31P NMR and X-ray diffraction. The following one-phase regions were found in the DOPA-water system: a reversed hexagonal liquid-crystalline (HII) phase up to about 35 wt % water and a lamellar liquid-crystalline (L alpha) phase between about 55 and 98 wt % water. The area per DOPA molecule was 36-65 A2 in the HII phase (10-40 wt % water) and 69 A2 in the L alpha phase (60 wt % water). DOPS and DOPG with 10-98 wt % water, and DPG with 20-95 wt % water formed an L alpha phase at temperatures between 25 and 55 degrees C. At temperatures above 55 degrees C, DPG with 20 and 30 wt % water formed a mixture of L alpha, HII, and cubic liquid-crystalline phases, the mole percent of lipid forming nonlamellar phases being smaller at 30 wt % water than at 20 wt % water. DPG with 10 wt % water probably formed a mixture of an L alpha phase and at least one nonlamellar liquid-crystalline phase at 25 and 35 degrees C, and a pure HII phase at 45 degrees C and higher temperatures. At water concentrations above about 50 wt % the 23Na quadrupole splitting was constant for all four lipid-water systems studied, implying that the counterion association to the charged lipid aggregates did not change upon dilution. These experimental observations can be described with an ion condensation model but not with a simple equilibrium model. The fraction of counterions located close to the lipid-water interface was calculated to be greater than 95%. The 2H and 23Na NMR quadrupole splittings of 2H2O and sodium counterions, respectively, indicate that the molecular order in the polar head-group region decreases for the L alpha phase in the order DOPA approximately DPG greater than DOPS greater than DOPG. PMID- 1932020 TI - Structure-function relationships of curaremimetic neurotoxin loop 2 and of a structurally similar segment of rabies virus glycoprotein in their interaction with the nicotinic acetylcholine receptor. AB - Peptides corresponding to portions of curaremimetic neurotoxin loop 2 and to a structurally similar segment of rabies virus glycoprotein were synthetically modified in order to gain information on structure-function relationships of neurotoxin loop 2 interactions with the acetylcholine receptor. Binding of synthetic peptides to the acetylcholine receptor of Torpedo electric organ membranes was assessed by measuring their ability to inhibit the binding of 125I alpha-bungarotoxin to the receptor. The peptides showing the highest affinity for the receptor were a peptide corresponding to the sequence of loop 2 (residues 25 44) of Ophiophagus hannah (king cobra) toxin b (IC50 = 5.7 x 10(-6) M) and the structurally similar segment (residues 173-203) of CVS rabies virus glycoprotein (IC50 = 2.6 x 10(-6) M). These affinities were comparable to those of d tubocurarine (IC50 = 3.4 x 10(-6) M) and suberyldicholine (IC50 = 2.5 x 10(-6) M). These results demonstrate the importance of loop 2 in the neurotoxin interaction with the receptor. N- and C-terminal deletions of the loop 2 peptides and substitution of residues invariant or highly conserved among neurotoxins were performed in order to determine the role of individual residues in binding. Residues 25-40 are the most crucial in the interaction with the acetylcholine receptor. Modifications involving Lys-27, Trp-29, Phe-33, Arg-37, and Gly-38 reduced affinity of binding. R37D and F33T modifications reduced the affinity of alpha-bungarotoxin residues 28-40 by an order of magnitude. Arg-37 may correspond to the positively charged quaternary ammonium group and Phe-33 to the hydrophobic acetyl methyl group of acetylcholine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932021 TI - Tubulin-G protein interactions involve microtubule polymerization domains. AB - It has been suggested that elements of the cytoskeleton contribute to the signal transduction process and that they do so in association with one or more members of the signal-transducing G protein family. Relatively high-affinity binding between dimeric tubulin and the alpha subunits of Gs and Gi1 has also been reported. Tubulin molecules, which exist in solution as alpha beta dimers, have binding domains for microtubule-associated proteins as well as for other tubulin dimers. This study represents an attempt to ascertain whether the association between G proteins and tubulin occurs at one of these sites. Removal of the binding site for MAP2 and tau from tubulin by subtilisin proteolysis did not influence the association of tubulin with G protein, as demonstrated in overlay studies with [125I]tubulin. A functional consequence of that association, the stable inhibition of synaptic membrane adenylyl cyclase, was also unaffected by subtilisin treatment of tubulin. However, ring structures formed from subtilisin treated tubulin were incapable of effecting such inhibition. Stable G protein tubulin complexes were formed, and these were separated from free tubulin by Octyl-Sepharose chromatography. Using this methodology, it was demonstrated that assembled microtubules bound G protein quite weakly compared with tubulin dimers. The alpha subunit of Gi1 and, to a lesser extent, that of Go were demonstrated to inhibit microtubule polymerization. In aggregate, these data suggest that dimeric tubulin binds to the alpha subunits of G protein at the sites where it binds to other tubulin dimers during microtubule polymerization. Interaction with signal transducing G proteins, thus, might represent a role for tubulin dimers which is independent of microtubule formation. PMID- 1932022 TI - Characterization of lipid insertion into monomolecular layers mediated by lung surfactant proteins SP-B and SP-C. AB - Pulmonary surfactant proteins, SP-B and SP-C, if present in preformed monolayers can induce lipid insertion from lipid vesicles into the monolayer after the addition of (divalent) cations [Oosterlaken-Dijksterhuis, M. A., Haagsman, H. P., van Golde, L. M. G., & Demel, R. A. (1991) Biochemistry 30, 8276-8287]. This model system was used to study the mechanisms by which SP-B and SP-C induce monolayer formation from vesicles. Lipid insertion proceeds irrespectively of the molecular class, and PG is not required for this process. In addition to lipids that are immediately inserted from vesicles into the monolayer, large amounts of vesicles are bound to the monolayer and their lipids eventually inserted when the surface area is expanded. SP-B and SP-C are directly responsible for the binding of vesicles to the monolayer. By weight, the vesicle binding capacity of SP-B is approximately 4 times that of SP-C. For vesicle binding and insertion, the formation of close contacts between monolayer and vesicles is essential. SP-B and SP-C show very similar surface properties. Both proteins form extremely stable monolayers (collapse pressures 36-37 mN/m) of alpha-helical structures oriented parallel to the interface. In monolayers consisting of DPPC and SP-B or SP-C, an increase in mean molecular area is observed, which is mainly attributed to the phospholipid. This will greatly enhance the insertion of new lipid material into the monolayer. The results of this study suggest that the surface properties and the hydrophobic nature of SP-B and SP-C are important for the protein-mediated monolayer formation. PMID- 1932023 TI - Evidence from total internal reflection fluorescence microscopy for calcium independent binding of prothrombin to negatively charged planar phospholipid membranes. AB - Measurements to test for a proposed Ca2+-independent interaction of prothrombin with membranes containing acidic phospholipids are described. Fluorescein-labeled bovine prothrombin and its amino- and carboxy-terminal peptides, prothrombin fragment 1 and prethrombin 1, were added at various concentrations in the presence or absence of Ca2+ to the aqueous space bathing substrate-supported planar membranes composed of 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine (POPC), POPC/bovine brain phosphatidylserine (bovPS) (70:30 mol/mol), or POPC/1,2 dioleoyl-3-sn-phosphatidylglycerol (DOPG) (70:30 mol/mol). Total internal reflection fluorescence microscopy (TIRFM) at the membrane-solution interface showed a significant enhancement by acidic lipids of prothrombin and prothrombin fragment 1 binding in the presence of 5 mM Ca2+, with apparent dissociation constants of 0.4 and 1 microM, respectively. TIRFM measurements indicated that bovPS and DOPG also significantly enhanced the binding of fluorescein-labeled prothrombin to the planar membranes in the absence of Ca2+, with apparent dissociation constants (13-30 microM) at least an order of magnitude larger than the Ca(2+)-dependent constant for prothrombin binding. Association of prethrombin 1 but not prothrombin fragment 1 with membranes in the absence of Ca2+ was enhanced by the presence of bovPS in the membranes, which suggests that the Ca(2+)-independent binding site(s) is (are) in the prethrombin 1 but not the fragment 1 portion of prothrombin. PMID- 1932025 TI - The hypercycle. Coupling of RNA and protein biosynthesis in the infection cycle of an RNA bacteriophage. PMID- 1932024 TI - Heparin oligosaccharides enhance tissue-type plasminogen activator: a correlation between oligosaccharide length and stimulation of plasminogen activation. AB - The rate of plasminogen (Pg) activation by tissue-type Pg activator (t-PA) is enhanced by heparin-derived oligosaccharides. Kinetic analysis of the effects of heparin oligosaccharides, ranging in size from di- to dodecasaccharides, on Pg activation demonstrates that stimulation of the reaction is dependent on the size of the heparin oligosaccharides. Di- and tetrasaccharides enhance the activation through 2-fold increases in kcat and 4-fold decreases in Km. Hexasaccharide and larger oligosaccharides stimulate the reaction by increasing the kcat by as much as 4-fold, but do not affect the Km. Previous experiments have shown that lipoprotein(a) [Lp(a)] inhibits Pg activation by t-PA, but only in the presence of a template which enhances t-PA activity such as fibrinogen fragments or intact heparin. Similiarly, Lp(a) inhibits the enhancement of t-PA activity by the larger heparin oligosaccharides but has no effect on t-PA activity in the presence of di- and tetrasaccharides. The results of this study when considered with our previous observations (Edelberg & Pizzo, 1990) suggest that the enhancement in Pg activation by the smaller oligosaccharides is mediated exclusively via binding to t-PA while the larger oligosaccharides may interact with both t-PA and Pg. Furthermore, studies of Pg activation in the presence of both heparin oligosaccharides and fibrinogen fragments demonstrate that t-PA is stimulated preferentially by fibrinogen fragments. PMID- 1932026 TI - Direct identification of the active-site nucleophile in a DNA (cytosine-5) methyltransferase. AB - The overproduction, purification, and determination of the active-site catalytic nucleophile of the DNA (cytosine-5)-methyltransferase (DCMtase) enzyme M.HaeIII are reported. Incubation of purified M.HaeIII with an oligodeoxynucleotide specifically modified with the mechanism-based inhibitor 5-fluoro-2' deoxycytidine [Osterman, D. G., et al. (1988) Biochemistry 27, 5204-5210], in the presence of the cofactor S-adenosyl-L-methionine (AdoMet), resulted in the formation of a covalent DNA-M.HaeIII complex, which was purified to homogeneity. Characterization of the intact complex showed it to consist of one molecule of the FdC-containing duplex oligonucleotide, one molecule of M.HaeIII, and one methyl group derived from AdoMet. Exhaustive proteolysis, reduction, and alkylation of the DNA-M.HaeIII complex led to the isolation of two DNA-bound peptides--one each from treatment with Pronase or trypsin--which were subjected to peptide sequencing in order to identify the DNA attachment site. Both peptides were derived from the region of M.HaeIII containing a Pro-Cys sequence that is conserved in all known DCMtases. At the position of this conserved Cys residue (Cys71), in the sequence of each peptide, was found an unidentified amino acid residue; all other amino acid residues were in accord with the known sequence. It is thus concluded that Cys71 of M.HaeIII forms a covalent bond to DNA during catalytic methyl transfer. This finding represents a direct experimental verification for the hypothesis that the conserved Cys residue of DCMtases is the catalytic nucleophile [Wu, J. C., & Santi, D. V. (1987) J. Biol. Chem. 262, 4778 4786].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932027 TI - Carbon-13 nuclear magnetic resonance spectroscopy of lipids: differential line broadening due to cross-correlation effects as a probe of membrane structure. AB - We have obtained proton-coupled carbon-13 nuclear magnetic resonance (NMR) spectra of a variety of lipid-water and lipid-drug-water systems, at 11.7 T, as a function of temperature, using the "magic-angle" sample-spinning (MAS) NMR technique. The resulting spectra show a wide range of line shapes, due to interferences between dipole-dipole and dipole-chemical shielding anisotropy interactions. The differential line-broadening effects observed are particularly large for aromatic and olefinic (sp2) carbon atom sites. Coupled spectra of the tricyclic antidepressants desipramine and imipramine, in 1,2-dimyristoyl-sn glycero-3-phosphocholine-water mesophases, show well-resolved doublets having different line shapes for each of the four aromatic methine groups, due to selective averaging of the four C-H dipolar interactions due to rapid motion about the director (or drug C2) axis. 2H NMR spectra of [2,4,6,8-2H4]desipramine (and imipramine) in the same 1,2-dimyristoyl-sn-glycero-3-phosphocholine-water mesophase exhibit quadrupole splittings of approximately 0-2 and approximately 20 kHz, indicating an approximate magic-angle orientation of the C2-2H(1H) and C8 2H(1H) vectors with respect to an axis of motional averaging, in accord with the 13C NMR results. Selective deuteration of imipramine confirms these ideas. Spectra of digalactosyl diglyceride [primarily 1,2-di[(9Z,12Z,15Z)-octadeca 9,12,15-trienoyl ]-3- (alpha-D-galactopyranosyl-1-6-beta-D-galactopyranosyl)-sn glycerol]-H2O (in the L alpha phase) show a large differential line broadening for C9 but a reduced effect for C10, consistent with the results of 2H NMR of specifically 2H-labeled phospholipids [Seelig, J., & Waespe-Saracevic, N. (1978) Biochemistry 17, 3310-3315].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932028 TI - Secondary structure and topology of human interleukin 4 in solution. AB - Human interleukin 4 (IL-4) has been studied by 2D and 3D NMR techniques using uniformly 15N-labeled recombinant protein. Assignment of resonances for all but 3 of the 130 residues of the recombinant protein has been achieved, enabling the secondary structure of the protein to be defined. This consists of four major alpha-helical regions and one short section of double-stranded antiparallel beta sheet. Analysis of distance and angle restraints derived from NMR experiments has enabled the overall molecular topology to be determined. This is related to that found for other four-helix proteins but has several distinctive features including cross-linking of helices by means of three disulfide bonds and a short section of beta-sheet. The structural analysis gives support to the hypothesis that many helical cytokines have a common fold and provides a basis for understanding the biological function of IL-4. PMID- 1932029 TI - Engineering the hydrophobic pocket of carbonic anhydrase II. AB - Wild-type and mutant human carbonic anhydrases II, where mutations have been made in the hydrophobic pocket of the active site, have been studied by X-ray crystallographic methods. Specifically, mutations at Val-143 (the base of the pocket) lead to significant changes in catalytic activity and protein structure. The obliteration of a well-defined pocket in the Val-143----Phe and Val-143--- Tyr mutants results in significantly diminished enzyme activity [(5 x 10(4))-fold and (3 x 10(5))-fold, respectively]; however, the activity of the Val-143----His mutant is diminished less (10(2)-fold), and deepening the pocket in the Val-143-- -Gly mutant results in only a 2-fold decrease in activity [Fierke et al., 1991 (preceding paper in this issue)]. These results indicate that the hydrophobic pocket is important for substrate association with the enzyme, but there are probably several catalytically acceptable substrate trajectories through this region of the enzyme structure. Additionally, each mutant protein exhibits long range (ca. 10-15 A) compensatory structural changes which accommodate the Val-143 substitution. As such, the genetic-structural approach represented in this work serves as a three-dimensional paradigm for the redesign of specificity pockets in other protein catalysts. PMID- 1932030 TI - Purification and characterization of selenomethionyl thymidylate synthase from Escherichia coli: comparison with the wild-type enzyme. AB - Replacement of methionine (Met) residues by selenomethionine (SeMet) was recently shown to facilitate the crystallographic analysis of protein structure through the application of multi-wavelength anomalous diffraction techniques [Yang et al. (1990) Science (Washington, D.C.) 249, 1398-1405]. The availability of SeMet containing proteins provides an excellent opportunity to evaluate the effects of the complete replacement of Met by SeMet. We chose to compare the properties of selenomethionyl thymidylate synthase isolated from Escherichia coli DL41 (a methionine auxotroph) and wild-type (wt) enzyme obtained from E. coli Rue10. An improved purification procedure for thymidylate synthase was developed which permitted the isolation of 25 mg of pure protein from 2 g of E. coli in 90% yield in no more than 8 h. The pure wt and SeMet enzymes exhibited specific activities 40% higher than published values. Thermal stability studies at 30 degrees C in degassed buffer showed that the SeMet enzyme (t1/2 67 h) was 8-fold less stable than wt enzyme (t1/2 557 h). The half-lives for the latter enzymes in nondegassed buffers at 30 degrees C were decreased by 2-fold, thus indicating the sensitivity of the enzyme to dissolved oxygen. Both enzymes exhibited essentially the same kinetic and binding properties, including Km(dUMP) (1.2 x 10(-6) M), specificity constant (1.6 x 10(6) s-1 M-1), and Kd for 5-fluorodeoxyuridylate binding (1.2 nM) in covalent inhibitory ternary complexes. In addition, X-ray crystallographic analysis by difference Fourier synthesis showed there was no significant difference in conformation between the SeMet enzyme and the wt enzyme. PMID- 1932031 TI - Investigation of the functional role of tryptophan-22 in Escherichia coli dihydrofolate reductase by site-directed mutagenesis. AB - We have applied site-directed mutagenesis methods to change the conserved tryptophan-22 in the substrate binding site of Escherichia coli dihydrofolate reductase to phenylalanine (W22F) and histidine (W22H). The crystal structure of the W22F mutant in a binary complex with the inhibitor methotrexate has been refined at 1.9-A resolution. The W22F difference Fourier map and least-squares refinement show that structural effects of the mutation are confined to the immediate vicinity of position 22 and include an unanticipated 0.4-A movement of the methionine-20 side chain. A conserved bound water-403, suspected to play a role in the protonation of substrate DHF, has not been displaced by the mutation despite the loss of a hydrogen bond with tryptophan-22. Steady-state kinetics, stopped-flow kinetics, and primary isotope effects indicate that both mutations increase the rate of product tetrahydrofolate release, the rate-limiting step in the case of the wild-type enzyme, while slowing the rate of hydride transfer to the point where it now becomes at least partially rate determining. Steady-state kinetics show that below pH 6.8, kcat is elevated by up to 5-fold in the W22F mutant as compared with the wild-type enzyme, although kcat/Km(dihydrofolate) is lower throughout the observed pH range. For the W22H mutant, both kcat and kcat/Km(dihydrofolate) are substantially lower than the corresponding wild-type values. While both mutations weaken dihydrofolate binding, cofactor NADPH binding is not significantly altered. Fitting of the kinetic pH profiles to a general protonation scheme suggests that the proton affinity of dihydrofolate may be enhanced upon binding to the enzyme. We suggest that the function of tryptophan 22 may be to properly position the side chain of methionine-20 with respect to N5 of the substrate dihydrofolate. PMID- 1932032 TI - Cloning and sequencing of the gene for rubrerythrin from Desulfovibrio vulgaris (Hildenborough). AB - The gene coding for rubrerythrin from the sulfate-reducing bacterium Desulfovibrio vulgaris (Hildenborough) has been cloned and sequenced. Rubrerythrin is known to contain two types of iron sites: one rubredoxin-like FeS4 center in each of the two identical subunits and one hemerythrin-like diiron site per dimer [LeGall, J., et al. (1988) Biochemistry 27, 1636-1642]. The gene encodes a polypeptide of 191 amino acids, and a normal ribosome binding site is located 11-6 base pairs upstream from the translational start of the gene. There is no evidence for the presence of a leader sequence, suggesting a cytoplasmic location for the protein. The rubrerythrin gene is not part of any other known transcriptional unit in the D. vulgaris genome. The nucleotide sequence encodes four Cys residues, the minimum required for ligation to iron in rubredoxin. The pairs of Cys residues occur in Cys-X-X-Cys sequences as they do in rubredoxin, but the 12-residue spacing between the Cys pairs in rubrerythrin is less than half that in rubredoxins. A pair of Arg residues flanking one Cys residue may contribute to the much more positive reduction potential of the rubredoxin-like site in rubrerythrin compared to that of rubredoxin. While the amino acid sequence of rubrerythrin shows no significant overall homology with that of any known protein, the C-terminal region does share some homology with rubredoxin sequences. If folding of the rubredoxin-like amino acid sequence domain in rubrerythrin is similar to that in rubredoxins, then three His residues are brought into proximity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932033 TI - Coexpression of both alpha and beta subunits is required for assembly of regulated casein kinase II. AB - Casein kinase II is an ubiquitous serine-threonine kinase whose functional significance and regulation in the living cell are not clearly understood. The native enzyme has an oligomeric structure made of two different (alpha and beta) subunits with an alpha 2 beta 2 stoichiometry. To facilitate the study of the structure-activity relationship of the kinase, we have expressed its isolated subunits in a baculovirus-directed insect cell expression system. The resulting isolated recombinant alpha subunit exhibited a protein kinase catalytic activity, in agreement with previous observations [Cochet, C., & Chambaz, E. M. (1983) J. Biol. Chem. 258, 1403-1406]. Coinfection of insect cells with recombinant viruses encoding the two kinase subunits resulted in the biosynthesis of a functional enzyme. Active recombinant oligomeric kinase was purified to near homogeneity with a yield of about 5 mg of enzymatic protein per liter, showing that, in coinfected host cells, synthesis was followed, at least in part, by recombination of the two subunits with an alpha 2 beta 2 stoichiometry. The catalytic properties of the recombinant enzyme appeared highly similar to those previously observed for casein kinase II purified from bovine tissue. Access to the isolated subunits and to their alpha 2 beta 2 association disclosed that the beta subunit is required for optimal catalytic activity of the kinase. In addition, the beta subunit is suggested to play an essential role in the regulated activity of the native casein kinase II. This is clearly illustrated by the observation of the effect of spermine which requires the presence of the beta subunit to stimulate the kinase catalytic activity which is borne by the alpha subunit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932034 TI - Stability and sequence-specific DNA binding of activation-labile mutants of the human glucocorticoid receptor. AB - The stability and DNA-binding properties of activation-labile (act1) human glucocorticoid receptors (hGRs) from the glucocorticoid-resistant mutant 3R7.6TG.4 were investigated. These receptors are able to bind reversibly associating ligands with normal affinity and specificity, but become unstable during attempted activation to the DNA binding form [Harmon et al. (1984) J. Steroid Biochem. 21, 227-236]. Affinity labeling and immunochemical analysis demonstrated that act1 receptors are not preferentially proteolyzed during attempted activation. In addition, analysis of binding to calf thymus DNA showed that after loss of ligand, act1 receptors retain the ability to bind to DNA nonspecifically. A 370 bp MMTV promoter fragment containing multiple GREs and an upstream 342 bp fragment lacking GRE sequences were used to assess the binding of act1 hGR to specific DNA sequences. Immunoadsorption of hGR-DNA complexes after incubation with 32P-end-labeled fragments showed that both normal and act1 hGR bound selectively to the GRE-containing fragment in an activation-dependent manner. Binding of both normal and act1 hGRs could be blocked with a synthetic oligonucleotide containing a perfect palindromic GRE, but not with an oligonucleotide in which the GRE was replaced by an ERE. Analogous results were obtained for normal and act1 hGR activated in the absence of ligand, or after incubation with the glucocorticoid antagonist RU 38486. These results suggest that sequence-specific binding of the hGR does not require the presence of bound ligand and suggest a role for the ligand in trans-activation of hormonally responsive genes. PMID- 1932035 TI - The in situ aggregational and conformational state of the major coat protein of bacteriophage M13 in phospholipid bilayers mimicking the inner membrane of host Escherichia coli. AB - The major coat protein of bacteriophage M13 has been reconstituted into phospholipids with a composition comparable to that found in the host (Escherichia coli) inner membrane. Reconstitution experiments have revealed conditions in which the alpha-oligomeric state is favored over the beta-polymeric state. Discrimination between the two states of the membrane-bound coat protein (alpha-oligomeric and beta-polymeric states) has been achieved using high performance size-exclusion chromatography and circular dichroism. Interprotein electrostatic interactions, probably induced by head-tail binding, are initiated and facilitating the aggregation-related conformational change process, in which alpha-oligomeric coat protein is converted into beta-polymeric coat protein. A model for this beta-polymerization process of the coat protein is presented. The alpha-helical protein has been studied by the in situ Trp fluorescence quantum yield. This shows that the average distances between coat proteins decrease upon lowering the L/P ratio. In situ cross-linking reactions of the coat protein at high L/P ratios reveal a monomeric state, thus excluding specific aggregation of the coat protein. A monomeric state of detergent-solubilized coat protein is also observed using SDS-PAGE and SDS-HPSEC. On the basis of these results, the smallest in situ aggregational entity of the coat protein is proposed to be a monomer. This finding is discussed in relation to the functional state of the M13 coat protein in the membrane-bound assembly and disassembly processes during infection. PMID- 1932036 TI - New joint prediction algorithm (Q7-JASEP) improves the prediction of protein secondary structure. AB - The classical problem of secondary structure prediction is approached by a new joint algorithm (Q7-JASEP) that combines the best aspects of six different methods. The algorithm includes the statistical methods of Chou-Fasman, Nagano, and Burgess-Ponnuswamy-Scheraga, the homology method of Nishikawa, the information theory method of Garnier-Osgurthope-Robson, and the artificial neural network approach of Qian-Sejnowski. Steps in the algorithm are (i) optimizing each individual method with respect to its correlation coefficient (Q7) for assigning a structural type from the predictive score of the method, (ii) weighting each method, (iii) combining the scores from different methods, and (iv) comparing the scores for alpha-helix, beta-strand, and coil conformational states to assign the secondary structure at each residue position. The present application to 45 globular proteins demonstrates good predictive power in cross validation testing (with average correlation coefficients per test protein of Q7, alpha = 0.41, Q7, beta = 0.47, Q7,c = 0.41 for alpha-helix, beta-strand, and coil conformations). By the criterion of correlation coefficient (Q7) for each type of secondary structure, Q7-JASEP performs better than any of the component methods. When all protein classes are included for training and testing (by cross validation), the results here equal the best in the literature, by the Q7 criterion. More generally, the basic algorithm can be applied to any protein class and to any type of structure/sequence or function/sequence correlation for which multiple predictive methods exist. PMID- 1932037 TI - Interaction of influenza virus hemagglutinin with a lipid monolayer. A comparison of the surface activities of intact virions, isolated hemagglutinins, and a synthetic fusion peptide. AB - In the infectious entry pathway of influenza virus, the low pH of the endosomal compartment induces an irreversible conformational change in influenza virus hemagglutinin, leading to fusion of viral and endosomal membranes. In the current report, we characterized the low-pH-induced activation of hemagglutinin of influenza strain X31 by studying its interaction with a lipid monolayer. The surface activities of virions, of isolated hemagglutinins and its proteolytic fragments, and of a synthetic peptide mimicking the amino terminus of subunit 2 of hemagglutinin are compared. The data indicate that the surface activity of both virions and isolated hemagglutinin develop as a result of the low-pH-induced conformational change in hemagglutinin. The surface activity of isolated hemagglutinin is mainly caused by penetration into the lipid monolayer of protein domains other than the amino terminus of subunit 2 of hemagglutinin; domains in subunit 1 may be involved. The surface activity of virions appears to be a secondary effect of the conformational change and is explained by assuming a net transfer of viral lipids to the lipid monolayer. PMID- 1932038 TI - Is there a rate-limiting step before GTP cleavage by H-ras p21? AB - A slow fluorescence change of the complex between ras p21 and the fluorescent GTP analogue 2'(3')-O-(N-methylanthraniloyl)guanosine 5'-triphosphate (mGTP) has been postulated to be a signal arising from a step which is rate limiting and precedes the actual GTP hydrolysis reaction [Neal, S. E., Eccleston, J. F., & Webb, M. R. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3562-3565]. We have now shown that the rate of the fluorescence change is accelerated by GTPase-activating protein (GAP) in the same manner as that of the GTP cleavage reaction. In contrast, a faster fluorescence change of smaller amplitude seen in the complex between p21 and the uncleavable 2'(3')-O-(N-methylanthraniloyl)guanosine 5'-O-(beta,gamma imidotriphosphate) (mGppNHp) is not affected by GAP. The corresponding fluorescent derivative of guanosine 5'-O-(gamma-thiotriphosphate) (mGTP gamma S) shows a very slow fluorescence change after binding to p21, and this rate is also accelerated significantly by GAP. Hydrolysis of GTP gamma S is similarly slow, and it is accelerated by GAP in a similar manner to the fluorescence change. The results are interpreted to indicate that the fluorescence change occurs either at the hydrolysis step or on release of inorganic phosphate or thiophosphate but does not occur in a rate-limiting step preceding hydrolysis. PMID- 1932039 TI - Two-dimensional 1H NMR studies on HPr protein from Staphylococcus aureus: complete sequential assignments and secondary structure. AB - Complete sequence-specific assignments of the 1H NMR spectrum of HPr protein from Staphylococcus aureus were obtained by two-dimensional NMR methods. Important secondary structure elements that can be derived from the observed nuclear Overhauser effects are a large antiparallel beta-pleated sheet consisting of four strands, A, B, C, D, a segment SAB consisting of an extended region around the active-center histidine (His-15) and an alpha-helix, a half-turn between strands B and C, a segment SCD which shows no typical secondary structure, and the alpha helical, C-terminal segment S(term). These general structural features are similar to those found earlier in HPr proteins from different microorganisms such as Escherichia coli, Bacillus subtilis, and Streptococcus faecalis. PMID- 1932040 TI - Mitochondrial bioenergetics as affected by DDT. AB - The organochloride insecticide DDT (2,2-bis(p-chlorophenyl)-1,1-trichloroethane) depresses the phosphorylation efficiency of mitochondria as inferred from the decrease of respiratory control ratio (RCR) and P/O ratio, perturbations of transmembrane potential (delta psi) fluctuations associated with mitochondrial energization and phosphorylative cycle induced by ADP. DDT depresses the delta psi developed by energized mitochondria and prevents complete repolarization, that is delayed and resumed at a lower rate. The inhibitory action of DDT on phosphorylation efficiency may result from: (1) a direct effect on the ubiquinol cytochrome c segment of the redox chain; (2) direct action on the ATP-synthetase complex; (3) partial inhibition of the phosphate transporter. DDT preferentially interacts with phosphorylation process in relation to respiration. High concentrations of DDT induce destruction of the structural integrity of mitochondria. PMID- 1932041 TI - The rotenone-insensitive reduction of quinones and nitrocompounds by mitochondrial NADH:ubiquinone reductase. AB - The rotenone-insensitive reduction of quinones and aromatic nitrocompounds by mitochondrial NADH: ubiquinone reductase (complex I, EC 1.6.99.3) has been studied. It was found that these reactions proceed via a mixed one- and two electron transfer. The logarithms of the bimolecular rate constants of oxidation (TN/Km) are proportional to the one-electron-reduction potentials of oxidizers. The reactivities of nitrocompounds are close to those of quinones. Unlike the reduction of ferricyanide, these reactions are not inhibited by NADH. However, they are inhibited by NAD+ and ADP-ribose, which also act as the mixed-type inhibitors for ferricyanide. TN/Km of quinones and nitrocompounds depend on the NAD+/NADH ratio, but not on NAD+ concentration. They are diminished by the limiting factors of 2.5-3.5 at NAD+/NADH greater than 200. It seems that rotenone insensitive reduction of quinones and nitrocompounds takes place near the NAD+/NADH and ferricyanide binding site, and the inhibition is caused by induced conformational changes after the binding of NAD+ or ADP-ribose. PMID- 1932042 TI - A comment on the preparation of liposomes from and on the beta in equilibrium alpha acyl chain melting behaviour of rough mutant lipopolysaccharide. AB - We would like to comment on the investigations of Vaara, M., Plachy, W.Z. and Nikaido, H. (Vaara, M. et al. (1990) Biochim. Biophys. Acta 1024, 152-158) on the partitioning of hydrophobic probes in lipopolysaccharide bilayers. These authors reported that they did not succeed in preparing closed vesicles (liposomes) from rough mutant lipopolysaccharide. We describe the conditions under which lipopolysaccharide liposomes are formed most readily. We, furthermore, summarize data which strongly support the existence of thermotropic phase transitions of lipopolysaccharides (with transition temperatures lying in the range of 30-36 degrees C) contradictory to Vaara et al. who argue that such transitions are artefacts. Exemplary measurements of the beta in equilibrium alpha acyl chain melting for lipopolysaccharide from Escherichia coli deep rough mutant (strain F515) as compared to synthetic and natural phospholipids are presented using fluorescence spectroscopy, Fourier-transform infrared spectroscopy and differential scanning calorimetry. These results unequivocally prove the necessity to perform experiments at 37 degrees C for a determination of the outer membrane permeability under physiological conditions. PMID- 1932043 TI - Characterization of the unidirectional transport of carnitine catalyzed by the reconstituted carnitine carrier from rat liver mitochondria. AB - The carnitine carrier from rat liver mitochondria was purified by chromatography on hydroxyapatite and celite and reconstituted in egg yolk phospholipid vesicles by adsorbing the detergent on polystyrene beads. In the reconstituted system, in addition to the carnitine/carnitine exchange, the purified protein catalyzed a uni-directional transport (uniport) of carnitine measured as uptake into unloaded proteoliposomes as well as efflux from prelabelled proteoliposomes. In both cases the reaction followed a first-order kinetics with a rate constant of 0.023-0.026 min-1. Besides carnitine, also acylcarnitines were transported in the uniport mode. N-Ethylmaleimide inhibited the uni-directional transport of carnitine completely. The uniport of carnitine is not influenced by the delta pH and the electric gradient across the membrane. The activation energy for uniport was 115 kJ/mol and the half-saturation constant on the external side of the proteoliposomes was 0.53 mM. The maximal rate of the uniport at 25 degrees C was 0.2 mumol/min per mg protein, i.e. about 10 times lower than that of the reconstituted carnitine transport in exchange mode. PMID- 1932044 TI - Light microscopic localization of silver-enhanced liposome-entrapped colloidal gold in mouse tissues. AB - Silver-enhanced liposome-entrapped colloidal gold was developed for light microscopic localization of liposomes. Preparation of colloidal gold entrapped in liposomes was achieved by a modified method of Hong, et al. (1983) Biochim. Biophys. Acta 732, 320-323). In this report, a gold chloride/citrate solution of low pH (3.4) was used to inhibit the formation of gold granules during the liposome preparation. The diameter of most liposomes ranged from 80 to 100 nm. Following liposome preparation, the pH was adjusted to 6, and the temperature increased to 55 degrees C. The majority of the liposomes contained one to three gold particles. Liposomes were injected into mice via tail vein; 24 h later, tissues were collected. Sections were processed for silver enhancement of the gold particles and examined by light microscopy. Silver-enhanced gold particles were clearly observed in both liver and implanted tumor. Localization was confirmed by electron and fluorescence microscopy. Thus, we have shown that silver enhancement of colloidal gold liposomes is a direct and sensitive method for tracing the fate of liposomes in vivo, providing minimal background interference and a good definition of various cell types. PMID- 1932045 TI - Nucleoside uptake by red blood cells from a primitive vertebrate, the Pacific hagfish (Eptatretus stouti), is mediated by a nitrobenzylthioinosine-insensitive transport system. AB - Red blood cells from the Pacific hagfish (Eptatretus stouti) were found to possess a facilitated diffusion nucleoside transport system insensitive to inhibition by the nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR). Uridine uptake by this route was saturable (apparent Km 0.14 mM; Vmax 2 mmol/l cells per h at 10 degrees C), inhibited by inosine and adenosine, and blocked both by the vasodilator dipyridamole and by the thiol-reactive agent p chloromercuriphenylsulphonate. The properties of this carrier resemble closely those of NBMPR-insensitive nucleoside transport systems in some mammalian neoplastic cell lines and in rat red cells. The presence of this type of carrier in a primitive vertebrate suggests that such transporters have a broad biological distribution and that they pre-date or arose at an early stage of vertebrate evolution. PMID- 1932046 TI - Galactolipid multibilayers modified with xanthophylls: orientational and diffractometric studies. AB - Oriented multibilayers of chloroplast galactolipids: monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) modified with violaxanthin and zeaxanthin were examined by X-ray diffractometry and linear dichroism. The results obtained suggest that zeaxanthin, in contrast to violaxanthin, has a significant ordering effect on galactolipid bilayers. The best ordered system consists of DGDG and zeaxanthin. In this case, the angle between the long axis of zeaxanthin molecule and the normal to the plane of bilayers amounts to 9 degrees and system has a periodicity of 61.7 A. The analogous angles in systems MGDG + violaxanthin, MGDG + zeaxanthin and DGDG + violaxanthin are clearly wider (35 degrees, 17 degrees and 28 degrees, respectively) but diffractograms show no distinct maxima. PMID- 1932047 TI - Alterations in membrane dynamics elicited by amphiphilic compounds are augmented in plasmenylcholine bilayers. AB - The dynamics of binary mixtures of choline glycerophospholipids and lysophospholipids were examined by fluorescence spectroscopy to compare and contrast the effects of each subclass of lysophospholipids on plasmenylcholine and phosphatidylcholine membrane motional characteristics. The decrease in steady state anisotropy resulting from the introduction of lysoplasmenylcholine into plasmenylcholine bilayers was 4-6-fold greater than that manifest from the introduction of lysophosphatidylcholine into phosphatidylcholine bilayers (i.e., delta r = 0.017 vs. 0.004 or 0.011 vs. 0.002 at 5 C degrees and 10 C degrees above their phase transition temperatures, respectively). Lysoplasmenylcholine was also more potent than lysophosphatidylcholine in perturbing the dynamics of membrane bilayers comprised of phosphatidylcholine as measured by alterations in the steady-state anisotropy of the diphenylhexatriene probe. Finally, lipid matrices comprised of plasmenylcholine were uniformly more susceptible to amphiphilic perturbation (mediated by lysoplasmenylcholine, lysophosphatidylcholine or long chain acylcarnitine) than matrices comprised of phosphatidylcholine. Collectively, these results demonstrate that accumulation of plasmalogen catabolites resulting from activation of plasmalogen-selective phospholipases A2 can potentiate alterations in membrane dynamics during signal transduction in plasmalogen-enriched bilayers. PMID- 1932048 TI - Induction of cationic amino acid transport activity in mouse peritoneal macrophages by lipopolysaccharide. AB - The transport of cationic amino acids has been investigated in mouse peritoneal macrophages cultured in vitro. The transport activity for lysine was rather low in cells cultured for 1 h and increased slightly in cells cultured for 12 h. This increase varied with the serum lot used in the culture medium and was suppressed by polymyxin B, suggesting that the transport activity is induced by endotoxins in the serum. When the macrophages were cultured in the medium containing 1 ng/ml lipopolysaccharide, the transport activity for lysine increased by more than 10 fold. The transport activity for lysine induced by lipopolysaccharide has been characterized. Lysine was transported mainly by a Na(+)-independent, saturable system. The uptake of lysine was potently inhibited by extracellular cationic amino acids, but not by neutral amino acids tested. In addition, transport of lysine showed trans-stimulation. From these results, we have concluded that the transport activity for cationic amino acids is potently induced by lipopolysaccharide and that the characteristics of the induced activity is consistent with those of system y+. PMID- 1932049 TI - Surface changes induced by osmotic stress and its influence on the glycerol permeability in lipid bilayers. AB - The penetration rate of glycerol across lipid bilayers can be assayed dispersing liposomes filled with a 0.1 M glucose solution in an isotonic or a hypertonic solution of glycerol. The kinetic of glycerol permeation is found to be different in each of those cases. Liposomes dispersed above the phase transition temperature in hypertonic solutions show an increase in the surface polarization as measured by means of merocyanine 540. Under this condition, the permeation of glycerol shows a two-step kinetic which is indicative of a non-fickean diffusion process. In contrast, liposomes dispersed in isotonic solutions of the permeant show a fickean behavior. The changes in polarization of the membrane interface are ascribed to variations in the surface potential due to the osmotic collapse and the glycerol concentration in contact with the outer surface. The permeability of polar molecules can, in consequence, be considered as a function of the surface potential of the liposome which is congruent with previous data in literature reporting that water permeability increases as a function of the zeta potential of liposomes shrunken in hypertonic solutions. PMID- 1932050 TI - Partitioning behaviour of 1-hexanol into lipid membranes as studied by deuterium NMR spectroscopy. AB - Deuterium nuclear magnetic resonance (NMR) spectroscopy was used to study the partitioning behaviour of 1-hexanol specifically deuterated in the alpha-position into model lipid bilayers. In all systems studied, the observed deuterium NMR lineshapes were time-dependent. Initially, 1-hexanol-d2 gave rise to an isotropic deuterium resonance with a different chemical shift from that of aqueous 1 hexanol-d2. After equilibration over a period of days, a broader spectral component characteristic of a spherically-averaged powder-pattern was observed. The quadrupole anisotropy of the 1-hexanol-d2 giving rise to the broad spectrum depended upon the cholesterol content of the membrane. From quantitation of the anisotropic to isotropic deuterium NMR spectra, the partition coefficients of 1 hexanol-d2 in a number of bilayer systems (asolectin and phosphatidylcholine bilayers (the latter with and without cholesterol] were determined. The partitioning of 1-hexanol-d2 into red blood cell membranes, and a suspension of lipids extracted from red blood cell membranes, was also examined. It is suggested that 1-hexanol, and probably other lipophiles, can partition to either the bilayer surface or the bilayer interior in a time-dependent manner. PMID- 1932051 TI - Isolation and characterization of canalicular and basolateral plasma membrane fractions from human liver. AB - A method is described for the isolation of subfractions from human liver plasma membranes, enriched in canalicular domains (cLPM) and basolateral domains (blLPM), respectively, and the results are compared to those obtained with rat liver. The studies were performed in 18 human livers. The cLPM (isolated at densities 1.103-1.127 for human and 1.036-1.127 for rat cLPM) from human as well as rat liver showed a lower density than the blLPM (1.141-1.161 for human and 1.151-1.172 for rat blLPM). Human and rat blLPM were characterized by increased levels of (Na+/K+)-ATPase (relative enrichment 33 and 21, respectively). Both human and rat cLPM showed high specific activities of leucine aminopeptidase; relative enrichment factors were 42 and 31, respectively. Mg(2+)-ATPase and alkaline phosphatase, specific canalicular enzymes in rat liver, were only slightly enriched in the cLPM of human liver, which indicates that these enzymes are not suitable as marker enzymes for human liver cLPM. Both cLPM and blLPM of human and rat origin were only slightly contaminated with mitochondria, lysosomes, Golgi membranes and endoplasmic reticulum. Total recoveries of cLPM and blLPM were 0.02 mg protein/g liver each for the human membrane preparations, compared to 0.07 and 0.16 mg protein/g liver for the membranes prepared from rat liver. Analysis of membrane fluidity revealed that the human liver cLPM were more rigid than blLPM (mean difference in fluorescence polarization PDPH 0.024). They contained more cholesterol (0.43 vs. 0.30 mumol/mg protein) and phospholipids (0.54 vs. 0.39 mumol/mg protein, respectively), which was compatible to rat liver plasma membrane fractions. This study shows that besides similarities, there are several differences between human and rat liver plasma membrane fractions. PMID- 1932052 TI - Inhibition of sodium-phosphate cotransport in renal brush-border membranes with the stilbenedisulfonate, H2-DIDS. AB - Membrane proteins involved with sodium/phosphate cotransport across the renal brush border provide the sensitive control for phosphate homeostasis. The present study describes the inhibition of sodium/phosphate cotransport with the stilbenedisulfonate derivatives, DIDS and H2-DIDS. Preincubation of the rat brush border membrane vesicles with H2-DIDS led to the inhibition of sodium-dependent phosphate uptake with a half maximal concentration, IC50, of about 10 microM. The inhibition was irreversible supporting the notion that H2-DIDS forms covalent bonds with the cotransporter. The cotransporter could be protected by excess sodium phosphate but not sodium chloride, sodium sulfate, sodium succinate, sodium bicarbonate, nor sodium phosphonoformate. These observations suggest that the stilbenedisulfonates may be useful in labeling the sodium/phosphate cotransporter within renal brush-border membranes. PMID- 1932053 TI - A combined study of aggregation, membrane affinity and pore activity of natural and modified melittin. AB - The pore activity of melittin and several chemically modified derivatives has been investigated using conductance measurements on planar lipid bilayers and marker release from small unilamellar vesicles. The modifications included N terminal formylation, acetylation, succinylation and modification of the tryptophan residue. All of the compounds showed bilayer permeabilizing properties, though quantitative differences were evident. These comprised changes in the voltage dependence of the conductance, in the single-pore kinetics, in the concentration of aqueous peptide required to induce a given pore activity and in the apparent 'molecularity' reflected by the power law of its concentration dependence. A strong tendency for disrupting bilayers was not always correlated with strong pore activity. For a better understanding of these results, measurements of pore activity were complemented by studying the aggregation behavior in solution and the water-membrane partition equilibrium. Modifications of charged residues gave rise to significant changes in the aggregation properties, had virtually no influence on the partition coefficient. The latter decreased strongly, however, as a result of tryptophan modification. Analysis of the isotherms was consistent with the assumption that the arginine residues in melittin do not contribute very much to charge accumulation at the immediate membrane/water interface. PMID- 1932054 TI - Structural requirements of lysophospholipid-regulated mitochondrial Ca2+ transport. AB - Analogues of lysophosphatidylcholine, including PAF (platelet-activating-factor) and HePC (an experimental anticancer drug), were studied for their influence on mitochondrial Ca2+ transport and membrane potential. Lysophospholipids released Ca2+ from mitochondria and reduced the maximal Ca2+ uptake. The structure activity relations indicate that deprotonated head groups like phosphocholines yield active compounds while partially protonated head groups like phosphoethanolamines are essentially inactive. Structural requirements for the apolar part of the molecules were acyl or alkyl chain lengths of less than 18 carbon atoms at the C1-position of the glycerol backbone and residues of small size and/or low polarity at the C2-position. Choline lysophospholipids, but not ethanolamine lysophospholipids, may therefore induce mitochondrial Ca2+ efflux and become mediators of ischaemic tissue damage where dysregulated phospholipase A2 activity and an impairment of mitochondrial function are supposed to play a crucial role. PMID- 1932056 TI - Erythrocyte membrane fluidity in malignant hyperthermia. AB - Malignant hyperthermia (MH) is a rare but serious complication of general anesthesia that potentially carries a high mortality and morbidity. It is associated with excessive release of calcium into skeletal muscle following exposure to certain drugs, including the volatile general anesthetics. Since these are recognized membrane fluidizing agents it has been speculated that this condition might represent a generalized defect in membrane physical properties either at rest or inducible by fluidizing agents. If this hypothesis were found to be correct, malignant hyperthermia might conveniently be detected by examining membrane physical properties of easily accessible cells rather than the cumbersome method of muscle biopsy currently employed. To test this hypothesis we identified patients proven to be susceptible to MH by muscle biopsy and a cohort of patients not susceptible to MH as defined by negative muscle biopsy testing. Erythrocytes were isolated from both groups and membrane physical properties examined using conventional, widely available, steady-state fluorescence polarization techniques. Erythrocyte membranes were evaluated with multiple probes both in the basal condition and following fluidization with either increasing temperature or two concentrations of a fluidizing alcohol. We report, contrary to previous publications, that no discernable differences were detectable between MH-positive or negative patients. Thus, we find no evidence for a generalized membrane defect in MH and conclude that the determination of erythrocyte membrane physical properties, by these techniques, are of no use in the preoperative screening for this disorder. PMID- 1932055 TI - Inositol 1,4,5-trisphosphate directly opens diphtheria toxin channels. AB - Inositol 1,4,5-trisphosphate (IP3) is a soluble second messenger, which acts by cooperatively releasing Ca2+ into the cytosol from non-mitochondrial stores, probably by activating Ca(2+)-permeable channels. We demonstrate that submicromolar concentrations of IP3 can directly open the Ca(2+)-permeable diphtheria toxin channel, and that this occurs by IP3 binding to a specific site on the toxin protein. This provides a model for IP3-induced Ca2+ release and suggests that IP3-induced channel opening may play a role in diphtheria intoxication and in protein translocation across membranes. PMID- 1932057 TI - Investigation of monovalent cation influxes of diamide-treated human erythrocytes in solutions of different ionic strength. AB - Total and residual i.e. (ouabain + bumetanide + EGTA)-insensitive K+ as well as Na+ influxes were investigated in human erythrocytes before and after treatment with diamide (5 mM). In physiological and in low ionic strength solution these influxes were increased after diamide treatment. Diamide-treated cells do not exhibit significant differences between the total and residual influxes for both Na+ and K+. The diamide-induced cation fluxes in low ionic strength solution are significantly higher compared with the fluxes in physiological ionic strength solution. The diamide-induced K+ influx is not chloride-dependent, and replacement of NaCl by sodium methylsulfate does not significantly reduce this flux. A subsequent incubation of diamide-treated erythrocytes with dithioerythritol which restores the cellular glutathione level to its original value only partly decreases the enhanced K+ influx. From these results it can be concluded that electrodiffusion and K/Cl cotransport are not involved in the diamide-induced stimulation of the residual K+ influx of human erythrocytes. PMID- 1932058 TI - The plasmalemma redox system of a fresh-water alga and membrane electrical parameters. AB - In order to learn more details about the plasmalemma redox system in the alga Hydrodictyon reticulatum the electrophysiological characteristics of the plasma membrane as influenced by artificial electron acceptors were estimated. Ferricyanide anion as well as TTF+ depolarized the membrane potential, the effect being more marked in the dark than in the light. In the presence of ferricyanide the membrane resistance in the light was decreased by about 29% on the average, in the dark it remained unchanged. On the other hand, TTF+ brought about a large increase in membrane resistance, notwithstanding the light conditions. The results are discussed in view of the impairing influence of both electron acceptors on the active inflow of chloride ions (Rybova, R. et al. (1990) Bot. Acta 103, 404-407). The electrogenic outflow of electrons appears to make the largest contribution to the membrane depolarization. The inhibition of a pumping mechanism coupling the active uptake of Cl- in some way to the transmembrane electron flow is envisaged as a plausible explanation for membrane resistance increase by TTF+. PMID- 1932059 TI - Effect of amphotericin B and Cl- removal on basolateral membrane K+ conductance in frog corneal epithelium. AB - Increase in stromal K+ concentration from 4 to 79 mM in an in vitro preparation of the frog cornea, in Cl(-)-free solutions, did not change the apical membrane fractional resistance, fR0, or the transepithelial conductance, gt; it depolarized the intracellular potential, V0, by 38 mV and decreased the short circuit current, Isc by 2.9 microA/cm2. These changes were similar to those observed for the same increase in stromal K+ in control solutions except for the increase in gt in the latter. When stromal K+ was increased with 10(-5) M amphotericin B, AmB, in the tear solution, fR0 increased by 0.27 in control solutions and by 0.08 in Cl(-)-free solutions; respectively, gt increased by 0.40 and by 0.17 mS/cm2; Isc decreased by 12 and by 11 mS/cm2; V0 depolarized by 9 and by 9.5 mV. These results support the concept that: (i) entrance of Cl- into the cell is responsible in part for the bioelectrical changes observed when stromal K+ is increased; and (ii) AmB decreases the partial K+ conductance in the basolateral membrane of the frog cornea epithelium by a decrease in intracellular K+. PMID- 1932060 TI - Effects of hyperosmotic medium on hepatocyte volume, transmembrane potential and intracellular K+ activity. AB - Hepatocyte transmembrane potential (Vm) behaves as an osmometer and varies with changes in extracellular osmotic pressure created by altering the NaCl concentration in the external medium (Howard, L.D. and Wondergem, R. (1987) J. Membr. Biol. 100, 53). We now have demonstrated similar effects on Vm by increasing external osmolality with added sucrose and not altering ionic strength. We also have demonstrated that hyperosmotic stress-induced depolarization of Vm results from changes in membrane K+ conductance, gK, rather than from changes in the K+ equilibrium potential. Vm and aKi of hepatocytes in liver slices were measured by conventional and ion-sensitive microelectrodes, respectively. Cell water vols. were estimated by differences in wet and dry weights of liver slices after 10-min incubations. Effect of hyperosmotic medium on membrane transference number for K+, tK, was measured by effects on Vm of step changes in external [K+]. Hepatocyte Vm decreased 34, 52 and 54% when tissue was superfused with medium made hyperosmotic with added sucrose (50, 100 and 150 mM). Correspondingly, aKi increased 10, 18 and 29% with this hyperosmotic stress of added sucrose. Tissue water of 2.92 +/- 0.10 kg H2O/kg dry weight in control solution decreased to 2.60 +/- 0.05, 2.25 +/- 0.06 and 2.22 +/- 0.05 kg H2O/kg dry weight with additions to medium of 50, 100 and 150 mM sucrose, respectively. Adding 50 mM sucrose to medium decreased tK from 0.20 +/- 0.01 to 0.05 +/- 0.01. Depolarization by 50% with hyperosmotic stress (100 mM sucrose) also occurred in Cl-free medium where Cl- was substituted with gluconate. We conclude that hepatocytes shrink during hyperosmotic stress, and the aKi increases. The accompanying decrease in Vm is opposite to that expected by an increase in aKi, and at least in part results from a concomitant decrease in gK. Changes in membrane Cl- conductance most likely do not contribute to osmotic stress-induced depolarization, since equivalent decreases in Vm occurred with added sucrose in cells depleted of Cl- by superfusing tissue with Cl-free medium. PMID- 1932061 TI - Inhibition of glucose transport in human erythrocytes by ubiquinone Q0. AB - Searches of the protein data bases revealed limited homologies between several regions of the human erythrocyte glucose transporter containing a relative abundance of hydrogen-bonding amino-acid side chains, and proteins of the NADH ubiquinone oxidoreductase family. This raised the possibility the binding sites for glucose and ubiquinone may be similar in the respective proteins. Experimental studies demonstrated that ubiquinone Q0 does in fact inhibit both glucose entry and glucose exit in human erythrocytes with kinetics consistent with the existence of ubiquinone binding sites at both the exofacial and endofacial sides of the transporter. Glucose transport was also inhibited by the water-soluble tryptophan-inactivating agent, dimethyl(2-hydroxy-5 nitrobenzyl)sulphonium bromide, and this is consistent with the presence of tryptophan residues in two of the exofacial amino-acid sequences proposed as candidates for involvement in glucose binding sites. PMID- 1932062 TI - Electrostatic interaction of poly(L-lysine) with dipalmitoylphosphatidic acid studied by X-ray diffraction. AB - Structure of dipalmitoylphosphatidic acid (DPPA) bilayers in the presence of poly(L-lysine) is proposed from the results of X-ray diffraction obtained by a storage phosphor detector with a high resolution called an imaging plate. The small-angle X-ray diffraction pattern exhibits that DPPA/poly(L-lysine) complex forms a highly ordered multilamellar structure. The electron density profile of the DPPA/poly(L-lysine) complex draws that only one poly(L-lysine) layer is intercalated between the neighboring DPPA bilayers. The wide-angle X-ray diffraction pattern suggests that the presence of poly(L-lysine) hardly affects the nature of hydrocarbon chain packing in the DPPA bilayers. The X-ray reflection from the DPPA/poly(L-lysine) complex indicates that the poly(L-lysine) molecules adopt a beta-sheet conformation on the surface of the DPPA bilayers. The both surface areas occupied by a headgroup of the DPPA and by a lysine residue in poly(L-lysine) are estimated from the observed spacings. The number ratio of lysine residues to DPPA headgroups per unit area is greater than unity. Therefore, one DPPA headgroup interacts with more than one lysine residue electrostatically, i.e., the electric charge distributions in both the surface of a DPPA bilayer and the poly(L-lysine) beta-sheet are incommensurate. PMID- 1932063 TI - Lipid-dependent membrane enzymes. Kinetic modelling of the activation of protein kinase C by phosphatidylserine. AB - A previously developed kinetic theory for lipid-dependent membrane enzymes (Sandermann, H. (1982) Eur. J. Biochem. 127, 123-128) is used to examine the activation of protein kinase C by phosphatidylserine. Hill-coefficients ranging up to 11 have been reported for activation in mixed micelles with Triton X-100. On the basis of this uniquely high degree of cooperativity, protein kinase C has been postulated to represent a new class of lipid-dependent membrane enzymes (Newton, A. and Koshland, D.E., Jr. (1989) J. Biol. Chem. 264, 14909-14915). In contrast, activation in the absence of Triton X-100 has led to Hill-coefficients of only less than or equal to 2.6. In order to resolve the apparent discrepancy, activation is now considered to involve binding of PS monomers to interacting sites on the enzyme, a non-activating PS trapping process also occurring in the presence of Triton X-100. Estimates for trapping are made for several sets of published data for micellar activation. The kinetic model developed here successfully fits each data set using a Hill-coefficient of only 3.0. An influence of Ca2+/ions or of a two-step mechanism of lipid-protein interaction are considered as possible molecular explanations. It is concluded (i) that lipid activation of protein kinase C may proceed without unique cooperativity and (ii) that ligand trapping could provide another means for 'threshold-type' kinetic regulation of membrane enzyme and receptor systems. PMID- 1932064 TI - Solubilization and partial purification of the thiazide diuretic receptor from rabbit renal cortex. AB - This study was designed to solubilize, characterize and begin to purify the thiazide-sensitive Na/Cl transporter from mammalian kidney. Metolazone, a thiazide-like diuretic drug, binds to receptors in rat renal cortex closely related to the thiazide-sensitive Na/Cl transport pathway of the renal distal tubule. In the current study, [3H]metolazone bound to receptors in rabbit renal cortical microsomes. The portion of [3H]metolazone binding that was inhibited by hydrochlorothiazide reflected binding to a high-affinity class of receptor. The affinity (Kd 2.0 +/- 0.1 nM) and number (Bmax = 0.9 +/- 0.4 pmol/mg protein) of high-affinity receptors in rabbit renal cortical membranes were similar to values reported previously for rat. When proximal and distal tubule fragments were separated by Percoll gradient centrifugation, receptors were restricted to the fraction that contained distal tubules. When compared with cortical homogenates, receptor density was enriched 12-fold by magnesium precipitation and differential centrifugation. The zwitterionic detergent CHAPS solubilized 25-35% of the receptors (at 6 mM). Chloride inhibited and Na stimulated binding of [3H]metolazone to solubilized high-affinity receptors. The receptors could be purified significantly by hydroxyapatite chromatography and size exclusion high performance liquid chromatography (HPLC). The combination of magnesium precipitation and differential centrifugation, hydroxyapatite chromatography, and size exclusion HPLC resulted in a 213-fold enrichment of receptors, compared to renal cortical homogenate. The current results indicate that thiazide receptors from rabbit kidney share characteristics with receptors from rat, and that rabbit receptors can be solubilized in CHAPS and purified significantly by hydroxyapatite chromatography and size exclusion HPLC. PMID- 1932065 TI - Improved stability of rabbit and rat intestinal brush border membrane vesicles using phospholipase inhibitors. AB - The initial rates of Na(+)-dependent D-aspartate and D-glucose uptakes were shown to decline from the time of resuspension of brush border membrane vesicles isolated from rabbit and rat jejunum by standard divalent cation precipitation procedures. The former were however more stable than the latter and followed quite closely the decrease in the intravesicular volume, thus suggesting that the loss of transport activity may involve both nonspecific opening of the vesicles and either direct or indirect specific inactivation of the transporters. Uptake rates for both substrates did tend to stabilize at 6-24 h from resuspension, however this final 'next day' uptake activity was too low to be of practical use in kinetic studies. Freezing aliquots of rabbit jejunal vesicles in liquid N2 until the time of assay resulted in complete stabilization of D-glucose uptake. A modified homogenate buffer designed to inhibit a broad spectrum of phospholipase activities resulted in a partial stabilization of glucose transport by rabbit jejunal vesicles with, on average, an over 6-fold enrichment in the 'next day' stable specific activity of uptake as compared to unfrozen vesicles. The modified homogenate buffer also improved the stability and the 'next day' specific activities of D-glucose uptake in rat jejunal brush border vesicles and D aspartic acid uptake in rabbit jejunal vesicles. It also completely stabilized the intravesicular volume in the latter preparation. An evaluation of the kinetic parameters of Na(+)-dependent D-glucose transport in rabbit vesicles prepared from either the standard homogenate media and frozen in liquid N2 or the modified media and allowed to stabilize overnight, revealed a single transport system with a Km of 0.31-0.32 mM as the best model to fit the data. As such the modifications to the homogenate media do not appear to effect the functional properties of D glucose transport in the membrane. While being less efficient in stabilizing the vesicles than the rapid freezing protocol, it is shown that the modified homogenate should however be preferred when dealing with slowly permeant ions like choline since it provides in this case the only alternative to reliable measurement of uptake rates across a stable and equilibrated vesicle preparation. PMID- 1932066 TI - A K(+)-selective channel in the colonic carcinoma cell line: CaCo-2 is activated with membrane stretch. AB - CaCo-2 is a human colonic carcinoma cell line which becomes differentiated in culture to form a polarized epithelium exhibiting several of the functional characteristics of native colonic tissue. In the present study, CaCo-2 cells have been used for a patch-clamp study of colonic ion conductance pathways. A large, 120 pS K(+)-selective channel was found in cells forming subconfluent monolayers in culture. Unlike Maxi-K+ channels found in other epithelial cells, this channel was not activated with elevations in cytosolic Ca2+. Channel activity was stimulated with membrane depolarization and most markedly with membrane stretch. The application of negative pressure (20 mm-Hg) to both cell-attached and excised, inside-out membrane patches caused a burst of channel activity which disappeared within seconds of suction removal. Single-channel conductance of the pressure-activated channel was decreased when quinine (100 microM) was present in the patch pipette. PMID- 1932067 TI - Ricin B-chain promotes the internalisation of liposomal contents into rat hepatoma cells. AB - Ricin B-chain covalently attached to liposomes has been shown to promote the binding of the liposomes to rat hepatoma cells through its galactosyl binding site. Internalisation of the bound liposomes is demonstrated by the cytotoxicity of methotrexate-containing liposomes, the transfection of cells with targeted liposomes containing pSV2-neo DNA and the intracellular activity of an enzyme encapsulated in liposomes targeted with the ricin B-chain. PMID- 1932068 TI - Rabbit muscle tetrameric D-glyceraldehyde-3-phosphate dehydrogenase is locked in the asymmetric state by chemical modification of a single arginine per subunit. AB - Modification of a single arginine residue per subunit of rabbit muscle tetrameric D-glyceraldehyde-3-phosphate dehydrogenase by 2,3-butanedione converts the enzyme into the form which retains 5-7% of the original activity and manifests cooperative properties that are absent in the native enzyme. It exhibits half-of the-sites reactivity towards the natural substrate D-glyceraldehyde-3-phosphate. Titration of the modified enzyme with DTNB reveals only two instantaneously reacting SH groups, the total amount of SH groups approaching nine per tetramer. In the presence of 8 M urea, an additional seven SH groups become accessible to DTNB. This suggests that the arginine modification imposes some conformational constraints which affect the microenvironment of the active site cysteine residues in two subunits of the tetramer. The changes do not influence the interaction between the essential cysteine residue and NAD+ which is responsible for the change transfer complex formation, since the molar extinction coefficient of the apoenzyme-NAD+ complex, epsilon 360, was not altered upon the arginine modification. The native and close to four in the case of the native enzyme and about three with the modified one. The apparent pK values of Cys-149 within the functioning active centers of the tetramer were determined from the pH profiles of the inactivation rates in presence of iodoacetamide. The apparent pKa of the essential thiols was found to change upon enzyme modification from 9.44 to 10.07 in the apoenzyme and from 9.17 to 9.36 in the holoenzyme. The apparent pKa of the arginine residue determined from the pH dependence of the inactivation rate was equal to 9.0 and did not change upon apo-holo enzyme transition. PMID- 1932069 TI - The conformation of echinomycin in DMSO solution. AB - The conformation of the antibiotic echinomycin in DMSO solution has been determined from two-dimensional NMR and distance geometry calculation with distance constraints. Five converged conformations were calculated with NOE distance constraints followed by restraint energy minimization. PMID- 1932070 TI - Characterisation of oligosaccharides from Drosophila melanogaster glycoproteins. AB - An analysis of the released oligosaccharides from a membrane glycoprotein preparation of third instar larvae (3rdIL), and purified larval serum protein 2 (LSP2) from Drosophila melanogaster was performed. Sequential exoglycosidase digestion in combination with high-resolution gel permeation chromatography and partial acetolysis indicated the presence of two series of oligomannosides; one of these series was unusual and characterized by the presence of a core alpha 1-6 linked fucose, the other was a typical mammalian oligomannose series containing the following isomers -D1, -D2, -D12, -D123 and -CD123 as well as the unprocessed Man9GlcNAc2 structure. Conventional oligomannose could only be detected in the LSP2 sample. This study opens the way to use powerful molecular and classical genetic techniques to analyse the control and functional significance of glycosylation in higher organisms. PMID- 1932071 TI - Characterisation of the binding sites for Escherichia coli heat-labile toxin type I in intestinal brush borders. AB - Intestinal brush borders from Wistar rats contained a total of 20-30-times more binding sites for Escherichia coli heat-labile enterotoxin (LT-1) than for cholera toxin (CT). The results suggest that LT-1 binds to sites in addition to ganglioside GM1, the binding site for CT. Brush border proteins were separated by SDS-PAGE, blotted to nitrocellulose and the filters incubated with 125I-labeled toxins. [125I]LT-1 was shown to bind to a series of brush border galactoproteins ranging in size from 130-140 kDa. Binding was inhibited by unlabeled LT-1 (but not CT), and by ricin and free galactose. A number of brush border enzymes are large glycoproteins which can be solubilised by papain. The papain-solubilised sucrase-isomaltase complex was purified by affinity chromatography and shown to bind LT-1, as did the proteins in fractions enriched in maltase activity. However, such brush border galactoproteins do not account for all of the additional LT-1 binding sites. Thus, brush borders prepared from 1-15-day-old rabbits contained many more binding sites for LT-1 than CT despite the absence of any sucrase-isomaltase activity, and no [125I]LT-1 binding proteins could be detected by blotting. There was a marked variation in the number of LT-1 binding sites in different strains of rat, and between different species. PMID- 1932072 TI - Development of enzyme immunoassays for leukotrienes using acetylcholinesterase. AB - We have developed sensitive solid phase enzyme immunoassays (EIA) to analyze quantitatively leukotrienes (LTs) using acetylcholinesterase from Electrophorus electricus as a label for LTB4, LTC4 and LTE4. However, because of problems specific to LTs, we used different coupling procedures to prepare LTs conjugates necessary for the production of antibodies and for the preparation of enzymatic tracers. For the immunogens, all LTs were coupled to bovine serum albumin using glutaraldehyde (ethylene diamine was used to add an amino group to LTB4). Immunizations in rabbits were done following classical procedures. For the enzymatic tracers, succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate was selected to conjugate the LTs via their amino groups to acetylcholinesterase. Titers of the different antisera ranged from 1:30,000 (LTE4), 1:40,000 (LTC4) to 1:50,000 (LTB4) and sensitivities (IC50) were 5.5 pg, 4.3 pg and 2.4 pg, respectively. Cross reactivities were also examined against other LTs. Sensitivities and specificities of the different systems were dependent on the conditions of incubation (temperature). Validation of the technique was done (i) after spiking known amounts of LTC4 in plasma and measuring the substance added after prior extraction and purification, (ii) by analyzing the supernatant of human neutrophils suspended in buffer or in plasma, (iii) by measuring LTE4 in urine. Due to the background provided by these complex matrixes, quantitation was performed after addition of [3H]LTs for recovery, protein precipitation, extraction by Sep-PakR and purification by HPLC. Measurement of LTs can be done in biological fluids with the same ease and advantages as other enzyme immunoassays that we have previously developed for eicosanoids analysis. PMID- 1932073 TI - Cooperative stacking and hydrogen bond pairing interactions of fragment peptide in cap binding protein with mRNA cap structure. AB - The stacking and hydrogen bonding abilities of Trp-(Gly)n-Glu (n = 0 approximately 3) for the interaction with 7-methylguanine (m7G) base were examined by fluorescence and 1H-NMR methods, and it was shown that they correlate with the distance between the Trp and Glu residues, and become most significant when both residues are separated from each other by two Gly residues (n = 2). Based on this insight, the sequence conserved between the human and yeast cap binding proteins (CBPs) was surveyed, and the sequence of Trp-Glu-Asp-Glu (No. 102-105 in human CBP) was selected as a probable site for the binding with mRNA cap structure. Thus, the stacking and hydrogen bonding abilities of Trp-Glu-Asp Glu with m7G cap structure were examined by comparative experiments using its analogous peptides. The results showed that the fourth Glu residue is important not only for the construction of hydrogen bond pairing with m7G base but also for strengthening the stacking interaction between the Trp indole ring and m7G base. Taking account of the recognition analysis using the mutant CBP proteins by site directed mutagenesis (Ueda, H., Iyo, H., Doi, M., Inoue, M., Ishida, T., Morioka, H., Tanaka, T., Nishikawa, S. and Uesugi, S. (1991) FEBS Lett. 280, 207-210), this cooperative interaction could be important for the recognition of mRNA cap structure. PMID- 1932075 TI - Concomitant synthesis and degradation of glutamine in isolated rabbit kidney tubules. AB - When rabbit kidney tubules were incubated with 1 mM [1-14C]glutamine as substrate, a release of 14CO2 together with a net production of glutamine were observed. That glutamine utilization was masked by higher rates of concomitant glutamine synthesis was demonstrated by: (i) inhibiting glutamine synthesis; and (ii) measuring the specific radioactivity of [1-14C]glutamine which fell during incubation. PMID- 1932074 TI - Increased hyaluronate synthesis and changes in glycosaminoglycan ratios and molecular weight of proteoglycans synthesised by cultured cervical tissue from ewes at various stages of pregnancy. AB - Culture of cervical tissue with radiolabelled precursors showed that, in pregnant ewes, net hyaluronate synthesis increased between days 120-140 but that the marked polydispersity of hyaluronate remained unchanged. In the less sulphated of two proteoglycan populations, the proportion of heparan sulphate increased and that of dermatan sulphate decreased, while the less polydisperse more highly sulphated species showed a significant increase in molecular weight with pregnancy. PMID- 1932076 TI - Link between L-3-cyanoalanine synthase activity and differential cyanide sensitivity of insects. AB - L-3-Cyanoalanine synthase activity is clearly linked to differential cyanide tolerance of two insect species, the southern armyworm (more tolerant) and cabbage looper (less tolerant). Mitochondrial location of this enzyme explains the mitochondrial insensitivity to cyanide, and its induction becomes critical in the current explanation of differential insensitivity to cyanide. PMID- 1932077 TI - Purification and partial characterization of a shed 66 kDa melanoma-associated antigen identified by autologous antibody. AB - We have previously reported the isolation of a 66 kDa melanoma-associated antigen, identified by autologous antibody, in serum and unfractionated spent tissue culture media by Western blot analysis. The antigen, detected by autologous serum S150, was found to be broadly represented on melanoma, glioma, renal cell carcinoma, neuroblastoma and head and neck carcinoma cell lines. S150 did not react with bladder or colon carcinoma, fetal fibroblasts, pooled platelets, lymphocytes and red blood cells, autologous cultured lymphocytes or fetal calf serum. To further characterize the antigen, spent tissue culture media, obtained from autologous melanoma cell line, Y-Mel 84:420, was separated by an isoelectric focusing column. Unabsorbed control serum S150 was noted to have a maximum titer of 1:2040 against autologous melanoma cells as measured by protein A hemadsorption. Following isoelectric focusing the greatest decrease in autologous antibody titer (30-fold) occurred with fractions having a pI between 2 and 3. Further resolution of the antigen was accomplished with high-pressure ion exchange chromatography. One of these fractions showed a significantly higher concentration of antigen and was distinctly resolved from bulk serum albumin. Subsequent Western blot analysis, with autologous antibody, of the isolated antigen-containing fraction, confirmed the presence of a single 66 kDa band. Exposure of the antigen, purified by high-pressure ion-exchange chromatography, to neuraminidase ablated recognition by autologous antibody and suggests that sialic acid is present on the protein and may be part of the antigenic epitope. Binding of antigen, obtained following DEAE anion exchange chromatography, was noted to lectins derived from Triticum vulgaris, Dolichos biflorus and Lycopersicon esculentum. Preparative purification of the antigen was accomplished by anion exchange followed by lectin affinity chromatography with a Dolichos biflorus column. Antigen obtained following lectin affinity chromatography subjected to SDS-PAGE and silver stain revealed a single band at 66 kDa. We conclude that a melanoma-associated antigen detected by autologous antibody in spent tissue culture media is an unusually acidic glycoprotein (pI 2-3). PMID- 1932078 TI - Topological analysis of the pyridine nucleotide transhydrogenase of Escherichia coli using proteolytic enzymes. AB - The pyridine nucleotide transhydrogenase of Escherichia coli has an alpha 2 beta 2 structure (alpha: Mr, 54,000; beta: Mr, 48,700). Hydropathy analysis of the amino acid sequences suggested that the 10 kDa C-terminal portion of the alpha subunit and the N-terminal 20-25 kDa region of the beta subunit are composed of transmembranous alpha-helices. The topology of these subunits in the membrane was investigated using proteolytic enzymes. Trypsin digestion of everted cytoplasmic membrane vesicles released a 43 kDa polypeptide from the alpha subunit. The beta subunit was not susceptible to trypsin digestion. However, it was digested by proteinase K in everted vesicles. Both alpha and beta subunits were not attacked by trypsin and proteinase K in right-side out membrane vesicles. The beta subunit in the solubilized enzyme was only susceptible to digestion by trypsin if the substrates NADP(H) were present. NAD(H) did not affect digestion of the beta subunit. Digestion of the beta subunit of the membrane-bound enzyme by trypsin was not induced by NADP(H) unless the membranes had been previously stripped of extrinsic proteins by detergent. It is concluded that binding of NADP(H) induces a conformational change in the transhydrogenase. The location of the trypsin cleavage sites in the sequences of the alpha and beta subunits were determined by N- and C-terminal sequencing. A model is proposed in which the N-terminal 43 kDa region of the alpha subunit and the C-terminal 30 kDa region of the beta subunit are exposed on the cytoplasmic side of the inner membrane of E. coli. Binding sites for pyridine nucleotide coenzymes in these regions were suggested by affinity chromatography on NAD-agarose columns. PMID- 1932079 TI - FTIR studies of secondary structures of bovine insulin and its derivatives. AB - The amide I bands of the deconvolved FTIR spectrum of bovine insulin, despentapeptide (B26-B30) insulin and desoctapeptide (B23-B30) insulin in D2O solution have been assigned to alpha-helix, the 3(10) helix, irregular helix, extended chains, beta-turns and other secondary structures. From the peak areas the relative contents of these structures obtained are in general agreement with those calculated from the known structures of porcine insulin and DPI in the crystalline state. The main difference in the structure of DOI with those of insulin and DPI is the shortening of the helix segment and an extended chain for the C terminal segment in the B chain. PMID- 1932080 TI - Presence of human immunoglobulin G anti serum pancreatic elastase 1 autoantibodies and their influence on elastase 1 radioimmunoassay. AB - Human immunoglobulin G (IgG) anti human pancreatic elastase 1 autoantibodies were detected in sera of patients with pancreatic disorders. The characteristics of these anti elastase 1 autoantibodies and their influence on radioimmunoassay (RIA) for elastase 1 were investigated. They were placed in the IgG class by the double antibody method, and most were assumed to be of a monoclonal type from their elution profiles in gel filtration analysis. The presence of autoantibodies in serum caused an increase in apparent elastase 1 values and a decrease in the recovery of elastase 1 exogenously added to the serum. These results suggest that elastase 1 immunoassay data for autoantibody positive sera can cause misjudgement of clinical stages of patients. PMID- 1932081 TI - Horseradish peroxidase catalyzed oxidation of thiocyanate by hydrogen peroxide: comparison with lactoperoxidase-catalysed oxidation and role of distal histidine. AB - Horseradish peroxidase-catalysed oxidation of thiocyanate by hydrogen peroxide has been studied by 15N-NMR and optical spectroscopy at different concentrations of thiocyanate and hydrogen peroxide and at different pH values. The extent of the oxidation and the identity of the oxidized product of the thiocyanate has been investigated in the SCN-/H2O2/HRP system and compared with the corresponding data on the SCN-/H2O2/LPO system. The NMR studies show that (SCN)2 is the oxidation product of thiocyanate in the SCN-/H2O2/HRP system, and its formation is maximum at pH less than or equal to 4 and that the oxidation does not take place at pH greater than or equal to 6. Since thiocyanate does not bind to HRP at pH greater than or equal to 6 (Modi et al. (1989) J. Biol. Chem. 264, 19677 19684), the binding of thiocyanate to HRP is considered to be a prerequisite for the oxidation of thiocyanate. It is further observed that at [H2O2]/[SCN-] = 4, (SCN)2 decomposes very slowly back to thiocyanate. The oxidation product of thiocyanate in the SCN-/H2O2/LPO system has been shown to be HOSCN/OSCN- which shows maximum inhibition of uptake by Streptococcus cremoris 972 bacteria when hydrogen peroxide and thiocyanate are present in equimolar amounts (Modi et al. (1991) Biochemistry 30, 118-124). However, in case of HRP no inhibition of oxygen uptake by this bacteria was observed. Since thiocyanate binds to LPO at the distal histidine while to HRP near 1- and 8-CH3 heme groups, the role of distal histidine in the activity of SCN-/H2O2/(LPO, HRP) systems is indicated. PMID- 1932082 TI - Acid phospholipid vesicles produce conformational changes on the antitumour protein alpha-sarcin. AB - The antitumour protein alpha-sarcin interacts at neutral pH with acid phospholipid vesicles promoting their aggregation and fusion. This interaction produces conformational changes on the protein molecule. Circular dichroism and infrared spectroscopy have been used to analyze the secondary structure of the protein molecule. The obtained results show an increased alpha-helix content upon interaction with the lipid vesicles. Detergents and halogenated alcohols have also been considered as an approach to the study of the conformational changes produced upon alpha-sarcin-phospholipid vesicles interaction. SDS treatment as well as trifluoroethanol also increase the helical content of alpha-sarcin. Intrinsic fluorescence of the protein has also been measured for the analysis of the conformational changes produced. The above helicogenic treatments produce a decrease on the structural quenching in alpha-sarcin which is consistent with the existence of hydrophobic protein-lipid interactions. The observed conformational changes are interpreted in terms of a shielding from polar groups caused by the lipids, which promotes intrachain hydrogen bonding and decreased static quenching. The reported conformational changes are discussed in terms of electrostatic and hydrophobic interactions involved in the fusion of lipid vesicles promoted by alpha-sarcin, and potentially in the passage of the protein across membrane cells. PMID- 1932083 TI - A 23 kDa protein from rat sperm plasma membranes shows sequence similarity and phospholipid binding properties to a bovine brain cytosolic protein. AB - A 23 kDa protein that is a major component of rat epididymal secretions and sperm plasma membranes has been purified and partially sequenced. A data-base search revealed approximately 85% sequence similarity with a phosphatidyl-ethanolamine binding protein from bovine brain cytosol. The rat 23 kDa protein also showed selective affinity for phosphatidylethanolamine (Kd = 1.6 x 10(-5) M) with lower activity towards phosphatidylinositol and phosphatidylcholine. It is suggested that differential affinity of protein antigens towards asymmetrically aligned phospholipids in sperm plasma membranes could account for their organisation into specific regional domains. PMID- 1932084 TI - Immunoaffinity purification and partial amino acid sequence analysis of catechol O-methyltransferase from pig liver. AB - Monoclonal antibodies (mAbs) against the soluble form (S-COMT) of catechol-O methyltransferase (COMT, EC 2.1.1.6) were produced using a purified preparation of the enzyme from pig liver as antigen. The selected monoclonal antibodies recognized the enzyme with different capacities. One of them (Co60-1B/7) showed a significant cross reaction with S-COMT from rat and human liver. A protein band of 23 kDa was recognized by the mAbs on Western blots of the soluble fraction of pig liver. The mAbs were also able to recognize the membrane-bound form of the enzyme, which was found to be mainly localized in the microsomal fraction of pig and rat liver as well as of the human hepatoma cell line Hep G2. The protein bands detected in microsomes had a molecular mass of 26 kDa in pig and rat liver and displayed a slightly higher molecular mass (29 kDa) in the Hep G2 cell line. A single step method for the immunoaffinity purification of pig liver S-COMT was developed by using a Sepharose 4B column to which the mAb Co54-5F/8 was covalently coupled. Acid elution conditions were optimized to obtain the enzyme in active form with a good yield. SDS-PAGE analysis of the purified preparation revealed a single protein band with a molecular mass of 23 kDa with 154-fold enrichment in enzyme activity over the starting material. Since the N-terminus was blocked, purified enzyme preparations were cleaved with trypsin. Two fragments of 22 and 33 amino acids in length could be sequenced by Edman degradation. PMID- 1932085 TI - Influence of allosteric effectors on the heme conformation of dromedary ferrous nitrosylhemoglobin detected by XANES spectroscopy. AB - The changes of the Fe heme-active site conformation of dromedary (Camelus dromedarius) nitrosylhemoglobin (HbNO) induced by inositol hexakisphosphate (IHP) and chlofibric acid (CFA) have been studied by using X-ray absorption near-edge structure (XANES) spectroscopy. Structural information has been determined by multiple scattering analysis of the Fe K-edge XANES spectra. The proximal histidine is found to move away from iron centers by about 0.4 Angstrom on the average over the four hemes upon binding of CFA or stoichiometric amount of IHP. In molar excess of polyanion or in the simultaneous presence of IHP, CFA and chloride, the proximal histidine moves back to a position very close to that observed in pure buffer; yet, the structure modulation induced by the allosteric effectors is not completely reversible. Such findings parallel with the functional properties and the spectroscopic (e.g., EPR and absorbance) characteristics of HbNO. PMID- 1932086 TI - X-ray crystallographic conformational study of 5'-O-[N-(L-alanyl) sulfamoyl]adenosine, a substrate analogue for alanyl-tRNA synthetase. AB - In order to elucidate the substrate specificity of alanyl-tRNA synthetase, 5'-O [N-(L-alanyl)sulfamoyl]adenosine (Ala-SA), an analogue of alanyl-AMP, was chemically synthesized. Its binding ability is similar to that of the substrate based on the inhibitory activity for the aminoacylation of alanyl-tRNA synthetase. Taking advantage of the stable sulfamoyl bond of Ala-Sa, compared with the highly labile aminoacyl bond of alanyl-AMP, the molecular conformation of the former inhibitor was studied by X-ray single crystal analysis. Crystal data are as follows: C13H19N7O7S.2H2O, space group C2, a = 39.620(6), b = 5.757(1), c = 20.040(3) A, beta = 117.2(1) degrees, V = 4065(9) A3, Z = 8, and final R = 0.065 for 2785 independent reflections of F(2)0 greater than or equal to 2 sigma (F0)2. In the crystal, the molecule is in a zwitterionic state with the terminal amino group protonated and sulfamoyl group deprotonated, and takes an open conformation, where the L-alanine moiety is located far from the adenosine moiety with gauche/trans and trans orientations about the exocyclic C(4')-C(5') and C(5')-O(5') bonds, respectively. The conformation of the adenosine moiety is anti for the glycosyl bond and C(3')-endo for the ribose puckering, and alanine is in the usually observed trans region for the psi torsion angle. The molecular dimensions of the sulfamoyl group are nearly the same as those of the phosphate group. The biological significance of the observed Ala-SA conformation is discussed in relation with the molecular conformation of tyrosyl-AMP complexed with tyrosyl-tRNA synthetase. PMID- 1932087 TI - Purification and determination of the NH2-terminal amino acid sequence of mouse alpha-amylase secreted from Saccharomyces cerevisiae: correct processing of the secretion signal from pGKL killer 28 kDa precursor protein. AB - We have previously reported the construction of recombinant mouse salivary alpha amylase secretion vector in Saccharomyces cerevisiae utilizing novel yeast secretion signal derived from killer 28 kDa precursor protein. Here, we have first purified recombinant mouse alpha-amylase to homogeneity from the culture medium of S. cerevisiae, and determined its NH2-terminal amino acid sequence. The sequencing data indicated that the 28 kDa killer secretion signal-alpha-amylase fusion protein was cleaved accurately at its native processing site, and that both the core-glycosylated and non-glycosylated alpha-amylases possessed the same NH2-terminal amino acid sequences. PMID- 1932088 TI - Effects of carbohydrate depletion on the structure, stability and activity of glucose oxidase from Aspergillus niger. AB - Glucose oxidase from Aspergillus niger was purified to homogeneity by hydrophobic interaction and ion-exchange chromatography. Approx. 95% of the carbohydrate moiety was cleaved from the protein by incubation of glucose oxidase with endoglycosidase H and alpha-mannosidase. Cleavage of the carbohydrate moiety effected a 24-30% decrease in the molecular weight and a reduction in the number of isoforms of glucose oxidase. No significant changes were observed in the circular dichroism spectra of the deglycosylated enzyme. Other properties, such as thermal stability, pH and temperature optima of glucose oxidase activity and substrate specificity were not affected. However, removal of the carbohydrate moiety marginally affected the kinetics of glucose oxidation and stability at low pH. From these results it appears that the carbohydrate chain of glucose oxidase does not contribute significantly to the structure, stability and activity of glucose oxidase. PMID- 1932089 TI - Evaluation of the kinetic parameters of the activation of trypsinogen by trypsin. AB - Kinetic analysis of the mechanism of trypsinogen activation by trypsin under rapid equilibrium conditions and certain relationships between the rate constants are presented. The kinetic equations are valid from the beginning of the reaction. In addition, we suggest a procedure, based on the above equations, for the evaluation of the kinetic parameters of the reaction. This procedure is applied to a set of experimental data collected during the activation of bovine trypsinogen by trypsin at 30 degrees C (pH 8.1) in 0.01 M CaCl2. In this system, the amount of active enzyme increases exponentially, as expected from an autocatalytic process. The apparent rate constant, delta, governing this increase would vary linearly with the trypsinogen concentration, [Z]0, if no Michaelis complex was detectable. However, the increase in delta with [Z]0 is clearly non linear and fits a hyperbola (delta = k2[Z]0/(Kz + [Z]0)) well. PMID- 1932090 TI - Kinetic study of a cellobiase purified from Neocallimastix frontalis EB188. AB - A cellobiase was purified from the culture supernatant of Neocallimastix frontalis EB188. This enzyme possessed a molecular weight of 85,000 and an isoelectric point of 6.95. The enzyme rapidly hydrolyzed cellobiose, p nitrophenyl (pNP) beta-D-glucopyranoside (pNPG) and cellotriose and slowly hydrolyzed cellopentaose and salicin. The enzyme did not hydrolyze pNP alpha-D glucopyranoside or pNP beta-D-cellobioside. Substrate inhibition was observed when cellobiose or pNPG were used as the substrates and glucose production was measured. The kinetic parameters were: K = 0.053 mM, V = 5.88 U/mg of protein and Ki = 0.95 mM for cellobiose; K = 0.36 mM, V = 1.05 U/mg and Ki = 8.86 mM for pNPG. Substrate inhibition was not detected during the hydrolysis of pNPG when pNP production was measured. The kinetic parameters for pNPG were: K = 0.67 mM and V = 1.49 U/mg of protein. The presence of an enzyme.glucose.substrate complex and transglucosylation was evident during the catalysis. Glucose, cellobiose, glucono-delta-lactone, galactose, lactose, maltose and salicin acted as competitive inhibitors during the hydrolysis of pNPG with the apparent inhibition constants (Kis) of 4.8 mM, 0.035 mM, 0.062 mM, 28.5 mM, 0.38 mM, 15.0 mm and 31.0 mM, respectively. PMID- 1932091 TI - Alkali cation effect on carbonyl-hemoglobin's and -myoglobin's conformer populations when exposed to freeze-concentration of their phosphate-buffered aqueous solutions. AB - Freeze-concentrated aqueous phosphate-buffered (pH 6.8) solutions of carbonyl hemoglobin (HbCO) and -myoglobin (MbCO) were investigated by Fourier-transform infrared spectroscopy for the effect of alkali cation on the population of conformers. When using sodium phosphates as buffer components, HbCO was transformed from conformer III (at approximately 1951 cm-1) which is the dominant form at ambient temperatures, into conformer IV (at buffer concentration at a given temperature. The conformational changes started slightly below the temperature where ice began to crystallize and the remaining solution became freeze-concentrated, and they were reversible for HbCO. For MbCO in 0.5 M sodium phosphate buffer solution, however, they were irreversible and MbCO denatured completely. When potassium phosphate salts were used for preparing the buffer at the same pH of 6.8, little or no transformation of conformer III into conformer IV was observed. The conformational changes induced by sodium salts are attributed to a decrease in pH and it is shown by infrared spectroscopy that during freeze concentration drastic changes in composition of the two buffer components H2PO4-/HPO(2)4- occur, the acid component increasing strongly relative to the base component. Supersaturation is also important because change from conformer III to IV requires a minimum concentration of sodium salts: whereas 0.1 M sodium phosphate buffer concentration shows a strong effect, 0.03 M concentration does not and therefore behaves like a potassium phosphate buffer. PMID- 1932092 TI - Identification and purification of a calcium-binding protein from Bacillus subtilis. AB - A Ca(2+)-binding protein was identified in Bacillus subtilis in the log phase of growth. The molecular mass of this protein is about 38 kDa as estimated by polyacrylamide gel electrophoresis in the presence of SDS and by gel filtration. The protein was found to be resistant 10 min at 65 degrees C and was purified about 400 times, starting from heated crude extract, by conventional procedures. This novel protein is able to bind Ca2+ in the presence of an excess of MgCl2 and KCl both in solution and after SDS gel electrophoresis and electrotransfer. Since an impairment of the Ca2+ intake, in Bacillus subtilis, results in an impairment of chemotactic behavior (Matsushita, T. et al (1988) FEBS lett. 236, 437-440), 38 kDa protein may be involved in the regulation of chemotaxis. PMID- 1932093 TI - Liver-like alkaline phosphatase in the tissue-unspecific type enzyme found in rabbit organs. AB - Rabbit liver and kidney tissues are known to produce an intestinal-like alkaline phosphatase (IAP-like enzyme) as a dominant isozyme, with a minor isozyme of tissue-unspecific type (UAP), unlike humans and other mammalians. We investigated immunohistochemically and biochemically these unique isozymes in the rabbit liver and bone, and compared them with the human isozyme. In rabbit liver, UAP was found to be localized only in the apical part of the membrane of cells lining the bile duct, whereas IAP-like enzyme was found in the sinusoidal membrane of hepatocytes. Rabbit liver UAP was separated from IAP-like enzyme by DEAE cellulose column chromatography. Rabbit bone tissue contained only one UAP isozyme. The two UAPs were biochemically and physicochemically compared with human liver AP. Both UAPs reacted with an anti-human liver AP monoclonal antibody, not with an anti-human bone AP monoclonal antibody, indicating that both enzymes have the same antigenicity as human liver AP. Rabbit liver and bone UAPs had similar N-linked sugar-chain heterogeneities to the respective human enzymes. In addition, rabbit bone AP also had an O-linked sugar chain, as did human bone AP, unlike rabbit and human liver APs. PMID- 1932094 TI - Immunoreactive alpha A crystallin in rat non-lenticular tissues detected with a sensitive immunoassay method. AB - For the quantitative analysis of the A subunit of alpha crystallin (alpha A) in the lens and for the survey of possible existence of alpha A in the non lenticular tissues, we have established a highly sensitive and specific immunoassay method for alpha A. Antisera to alpha A were raised in rabbits with alpha A purified from bovine lens, or the C-terminal decapeptide (EEKPSSAPSS) of alpha A (alpha Apep). The antibodies to alpha A and alpha Apep were purified by the use of an alpha A-coupled Sepharose 4B column. The F(ab')2 fragments of purified anti-alpha A IgG were immobilized on polystyrene balls and the Fab' fragments of purified anti-alpha Apep IgG were labeled with beta-D-galactosidase from Escherichia coli. The minimum detection limit of the sandwich-type immunoassay using the two antibody preparations was less than 10 pg alpha A without any cross-reactivity with alpha B. By employing the present methods, it was found that a significant amount of immunoreactive alpha A was present in rat spleen and thymus. Very low levels of immunoreactive alpha A were detected in the rectum, caecum, liver, kidney, adrenal, cerebellum and brainstem. The immunoreactive alpha A in the spleen extract was purified partially (about 50% purity) by the use of anti-alpha Apep-coupled Sepharose. The concentration of alpha A in the spleen was less than 1 ng/mg protein before 3 weeks of age. After 5 weeks of age, however, it increased lineally reaching about 20 ng/mg protein by 18 weeks of age. Immunohistochemically, the alpha A was localized in the reticular cells in the spleen and thymus. PMID- 1932095 TI - Bovine N-acetyl-beta-D-glucosaminidase: affinity purification and characterization of its active site with nitrogen containing analogs of N acetylglucosamine. AB - Two N-acetylglucosaminidases were isolated from bovine kidney with a three step procedure featuring affinity purification on 2-acetamido-1,2,5-trideoxy-1,5 iminoglucitol (2-acetamido-1,2-dideoxynojirimycin, II). The major isoenzyme, Hex A, is an alpha, beta hetero-dimer (57 and 52 kDa) with isoelectric points from pH 5.3 to 6.6 and comprised about 80% of the total activity. Its kinetic properties with respect to discrimination between N-acetylglucosaminide, N acetylgalactosaminide and the corresponding 6-sulfate ester were similar to human hexosaminidase A. The minor isoenzyme, Hex B, a homodimer, isoelectric points 7.0 to 7.4, was similar to Hex A but was without detectable activity with methylumbelliferyl-N-acetyl-beta-glucosaminide-6-sulfate. Inhibition studies with Hex A were carried out with 2-acetamido-2,5-dideoxy-1,5-imino-D-glucopyranose (2 acetamido-2-deoxynojirimycin, (1), the corresponding 1,5-lactam (III), with II and its N,N-dimethyl derivative, and with 2-acetamido-2-deoxy-D-glucono-1,5 lactone (IV). In comparison with N-acetylglucosamine (Ki 1.9 mM) Hex A was inhibited 10(6)-fold better by I, 2600-fold better by II, 2900-fold better by III, and 55,000-fold better by IV. A slow approach to the inhibition equilibrium was observed with I and IV. For IV and Hex A it is the first example of a slow inhibition of a glycoside hydrolase by the corresponding glycono-1,5-lactone. The pH-dependence of Ki for the permanently cationic N,N-dimethyl II (15.4 microM (pH 3.5) to 0.47 microM (pH 7.0)) indicated that formation of the enzyme inhibitor complex is governed by deprotonation of a group with pKa 5.0. The results are discussed with respect to structural features and water accessibility of the active site. PMID- 1932096 TI - Recombinant mouse leukotriene A4 hydrolase: a zinc metalloenzyme with dual enzymatic activities. AB - Recombinant mouse leukotriene A4 hydrolase was expressed in Escherichia coli as a fusion protein with ten additional amino acids at the amino terminus and was purified to apparent homogeneity by means of precipitation, anion exchange, hydrophobic interaction and chromatofocusing chromatographies. By atomic absorption spectrometry, the enzyme was shown to contain one mol of zinc/mol of enzyme. Apparent kinetic constants (Km and Vmax) for the conversion of leukotriene A4 to leukotriene B4 (at 0 degree C, pH 8) were 5 microM and 900 nmol/mg per min, respectively. The purified enzyme also exhibited significant peptidase activity towards the synthetic amide alanine-4-nitroanilide. Km and Vmax for this reaction (at 37 degrees C, pH 8) were 680 microM and 365 nmol/mg per min, respectively. Apo-leukotriene A4 hydrolase, prepared by treating the enzyme with 1,10-phenanthroline, was virtually inactive with respect to both enzymatic activities, but could be reactivated by addition of stoichiometric amounts of zinc or cobalt. Exposure of the enzyme to leukotriene A4 resulted in a dose-dependent inactivation of both enzyme activities. PMID- 1932097 TI - Sphingolipids of a cestode Metroliasthes coturnix. AB - Sphingolipids of Metroliasthes coturnix were studied. The cestode contained no detectable amounts of sphingomyelin. The major glycosphingolipids found were monogalactosylceramide, galactosyl-alpha-1-4-galactosylceramide, galactosyl-beta 1-6-galactosyl-beta-1-6-galactosylceramide and galactosyl-beta-1-6-galactosyl beta-1-6-galactosyl-beta-1-6-galactosylce ramide. Their ceramides were mostly composed of C18-20 sphinganine or 4-D-hydroxysphinganine, which is N-acylated by extraordinarily long normal and 2-hydroxy acids such as C26 acid (range C16 to C30) except tetragalactosylceramide. The structure of glycosphingolipids was confirmed after their chromatographic separation into each molecular species using a novel analytical device, fast atom bombardment-mass spectrometry linked with reversed-phase high-performance liquid chromatography. PMID- 1932098 TI - Fatty acid specificity of bile salt-dependent lipase: enzyme recognition and super-substrate effects. AB - A putative fatty acid specificity of bile salt-dependent lipases (BSDLs) has been re-investigated. The strategy was to use two evolutionally distant, homologous BSDLs (from human and cod), and to investigate their hydrolysis of different fatty acid esters at different assay conditions affecting the physicochemical phase of the substrate. Depending on assay conditions, large variations were seen in the hydrolysis rate for esters of different fatty acids. The two enzymes displayed similar fatty acid specificity patterns, with small, but significant differences that were maintained at various assay conditions. Compared to the human enzyme, the cod enzyme showed a preference for hydrolysis of long-chain polyunsaturated fatty acyl esters (up to 22 carbons in length). On the other hand, the human enzyme hydrolysed esters of shorter chain saturated fatty acids at significantly higher rates compared to the cod enzyme. Changing physicochemical factors affecting the substrate phase induced large changes in fatty acid specificity that affected both enzymes in similar manners. It is concluded that though the aliphatic chains of the fatty acids may not be recognized by the enzymes, these chains indirectly affect the conformation or interfacial availability of the carboxyl ester bond in the substrate, and the enzymes show minor specificities for variations in these structures. PMID- 1932099 TI - Cholesterol efflux from macrophages mediated by high-density lipoprotein subfractions, which differ principally in apolipoprotein A-I and apolipoprotein A II ratios. AB - High-density lipoprotein (HDL) was fractionated by preparative isoelectric focussing into six distinct subpopulations. The major difference between the subfractions was in the molar ratio of apolipoprotein A-I to apolipoprotein A-II, ranging from 2.1 to 0.5. The least acidic particles had little apolipoprotein A II, were larger and contained the most lipid. The efflux capacity of the HDL subfractions was tested with mouse peritoneal macrophages and a mouse macrophage cell line (P388D1), either fed with acetylated low-density lipoprotein or free cholesterol. All the HDL subfractions were equally able to efflux cholesterol. The efflux was concentration dependant and linear for the first 6 h. The HDL subfractions bound with high affinity (Kd = 6.7-7.9 micrograms/ml) at 4 degrees C to the cell surface of P388D1 cells (211,000-359,000 sites/cell). Ligand blotting showed that all the HDL subfractions bound to membrane polypeptides at 60, 100, and 210 kDa. These HDL binding proteins may represent HDL receptors. In summary HDL particles, which differed principally in ratio of apolipoprotein A-I to apolipoprotein A-II behaved in a similar manner for both cholesterol efflux and cell surface binding. PMID- 1932100 TI - Characterization of pulmonary surfactant protein D: its copurification with lipids. AB - Surfactant protein D (SP-D) is a collagenous surfactant associated protein synthesized by alveolar type II cells. SP-D was purified from the supernatant of rat bronchoalveolar lavage fluids obtained by centrifugation at 33,000 x gav for 16 h. The contents of SP-D and SP-A in fractions obtained by the centrifugation of rat bronchoalveolar lavage were determined by enzyme-linked immunoassay. The total content of SP-D was approximately 12% of that of SP-A in these lavage fluids. 99.1% of SP-A was present in the 33,000g pellet, whereas 71.1% of SP-D was in the 33,000g supernatant. Analysis by high performance liquid chromatography reveals that lipids are copurified with isolated SP-D. Phosphatidylcholine accounted for 84.8% of the phospholipids copurified with SP D. Unlike SP-A, SP-D in the purified and delipidated form failed to compete with 125I-labeled SP-A for phosphatidylcholine binding, and to aggregate phospholipid liposomes. The present study demonstrates that lipids are copurified with SP-D, that SP-D and SP-A distribute differently in rat bronchoalveolar lavage fluids, and that SP-D in the purified and delipidated form does not exhibit interaction with lipids in the same fashion as SP-A. PMID- 1932101 TI - Comparison of effects of platelet-activating factor and tumour necrosis factor alpha on lipid metabolism in adrenalectomized rats in vivo. AB - The acute metabolic effects of platelet-activating factor (PAF) and tumour necrosis factor-alpha (TNF-alpha) were compared in sham-operated and adrenalectomized rats. PAF caused hyperglycaemia in sham-operated rats, whereas with TNF-alpha there was a slight decrease in blood glucose. Both PAF and TNF alpha resulted in marked hypoglycaemia in the adrenalectomized rats. Plasma insulin was depressed (about 50%) by PAF and TNF-alpha in sham-operated rats, whereas in the adrenalectomized rats the already low plasma insulin concentration was not significantly altered. Liver glycogen content was the same in control and treated sham-operated rats, but was considerably decreased (about 50%) in the adrenalectomized rats. In sham-operated rats, PAF and TNF-alpha increased plasma non-esterified fatty acids and triacylglycerols, suggesting increased lipolysis, whereas in adrenalectomized rats there was no significant increase in non esterified fatty acids with PAF, although it still occurred with TNF-alpha. This suggests that the lipolytic effect of TNF-alpha may be direct, whereas that of PAF is indirect, possibly via increased catecholamines in the sham-operated rats. The stimulation (about 3-fold) of hepatic fatty acid synthesis in vivo by PAF and TNF-alpha in sham-operated rats was still evident in the adrenalectomized rats, although the absolute increase was smaller. PAF, but not TNF-alpha increased (100%) sterol synthesis in adrenalectomized rats. It is concluded that PAF and TNF-alpha can increase hepatic lipogenesis in vivo in the absence of adrenal hormones and in the presence of a low plasma insulin. PMID- 1932102 TI - Relationships between fatty acid synthesis and lipid secretion in the isolated perfused rat liver: effects of hyperthyroidism, glucose and oleate. AB - Various studies on the effects of thyroid status on hepatic fatty acid synthesis have produced conflicting results. Several variables (e.g., plasma free fatty acid and glucose concentrations) are altered simultaneously by thyroid status and can affect fatty acid synthesis. To evaluate the effects of these variables, hepatic fatty acid synthesis (lipogenesis) was studied in isolated perfused livers from normal and triiodothyronine-treated rats. Livers were perfused with media containing either 5.5 or 25 mM glucose without fatty acid, or 5.5 mM glucose and 0.7 mM oleate. Rates of lipogenesis were determined by measurement of incorporation of 3H2O into fatty acids. Lipogenesis in livers from hyperthyroid animals exceeded that of controls, when perfused with 5.5 mM glucose with or without oleate. Perfusion with 25 mM glucose increased lipogenesis in both euthyroid and hyperthyroid groups to the same level, abolishing this difference between them. Perfusion with oleate reduced rates of lipogenesis by livers from euthyroid and hyperthyroid rats to a similar extent, but stimulated secretion of radioactive fatty acid in phospholipid and free fatty acid fractions. Oleate increased ketogenesis by livers from normal and triiodothyronine-treated rats, with higher rates of ketogenesis in the triiodothyronine-treated group. When oleate was omitted, ketogenesis in the presence of 5.5 mM glucose by the hyperthyroid group was similar to that of euthyroid controls, while ketogenesis was decreased in the hyperthyroid group relative to controls when perfused with 25 mM glucose. About 30% of the radioactivity incorporated into the total fatty acid of both groups was recovered in palmitate, with the remainder in longer chain saturated and unsaturated fatty acids. In both euthyroid and hyperthyroid groups, the ratio of triacylglycerol:phospholipid fatty acid radioactivity was not only less than predicted (based on synthetic rates of PL and TG) but also was decreased in perfusions with exogenous oleate compared to perfusions without oleate. In perfusions with oleate, both groups incorporated twice as much radioactivity into phospholipid as into triacylglycerol. The data suggest the following concepts: while hepatic fatty acid synthesis and oxidation are increased simultaneously in the hyperthyroid state, de novo synthesized fatty acids seem to be poorer substrates for oxidation than are exogenous fatty acids, and are preferentially incorporated into phospholipid, while exogenous fatty acids are better substrates for oxidation and esterification to triacylglycerol. The preferential utilization of de novo synthesized fatty acid for phospholipid synthesis may be an important physiologic adaptation insuring a constant source of fatty acid for membrane synthesis. PMID- 1932103 TI - Development of a human lung surfactant, derived from extracted amniotic fluid. AB - Using a surfactant preparation of human origin for the treatment of the respiratory distress syndrome (RDS) instead of an animal-derived surfactant will minimize immunological problems. Therefore we isolated surfactant material from human amniotic fluid. Protein and phospholipid fractions of extracted human amniotic fluid (HAFS) were separated by Lipidex 5000 or acidulated LH20 liquid chromatography systems. Fractions of HAFS, the phospholipid or the recombined phospholipid-protein fractions, were tested in the 27-day fetal rabbit model. The results were compared with the results of the corresponding fractions of extracted ovine lung lavage (EOS) and of the already clinically tested surfactant Curosurf. The in situ surface activity of HAFS, EOS, and of their combined phospholipid + protein fractions (200 mg/kg body wt.) resulted in a lung compliance which was significantly higher than the control (saline) values. The compliances of HAFS, EOS, their combined fractions, and Curosurf were similar, but the lung stability values (V5) differed significantly among these surfactant extracts. The best V5 values (greater than or equal to 0.020 ml/g body wt.) were found after installing EOS or its LH20 phospholipid + protein fractions. HAFS had a poor stabilizing capacity which increased significantly after Lipidex chromatography and even more after enrichment of the Lipidex material with 10% palmitic acid. The Lipidex HAFS + 10% palmitic acid surfactant is at present the best obtainable human surfactant extract. Further development is in progress for the clinical application of this surfactant in preterm neonates. PMID- 1932104 TI - The fate of arachidonic acid and linoleic acid in isolated working rat hearts containing normal or elevated levels of coenzyme A. AB - If myocardial levels of coenzyme A (CoA) are elevated, an increase in the rate of esterification of palmitate into myocardial triacylglycerols will occur. In this study, we determined the fate of linoleic acid and arachidonic acid in isolated working rat hearts containing normal or elevated levels of CoA. In hearts containing normal levels of CoA, oxidative rates (measured as 14CO2 production) of [14C]arachidonic acid were significantly lower than those of [14C]palmitic acid, whereas a significantly greater incorporation of [14C]arachidonic acid into myocardial neutral lipids (comprised predominantly of triacylglycerols) was seen when compared to hearts perfused with [14C]palmitic acid. In a second series of hearts, myocardial CoA levels were elevated by perfusing hearts with no carbon substrate, 15 microM pantothenate, 0.5 mM cysteine and 1 mM dithiothreitol, resulting in an increase in myocardial CoA levels from 553 +/- 2 to 918 +/- 63 nmol/g dry wt. Subsequent perfusion of hearts containing elevated CoA levels with 1.2 mM [3H]arachidonic acid or [14C]linoleic acid resulted in a significant increase in incorporation of both these fatty acids into myocardial neutral lipids compared to control hearts. Incorporation of these fatty acids into phospholipids was significantly lower than their incorporation into neutral lipids and was not affected by myocardial CoA levels. Linoleic acid oxidation was unaffected by increases in myocardial levels of CoA. If linoleic acid oxidation was inhibited by adding 5 mM pyruvate to the perfusate, no effect on the incorporation of [14C]linoleic acid into neutral lipids was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932105 TI - Plasma lecithin-cholesterol acyltransferase activity and cholesterol and phospholipid levels in premature newborn infants. AB - Lecithin-cholesterol acyltransferase (LCAT) activity has been suggested to play an important role in the regulation of lipid metabolism. The present study was undertaken to examine any relationship between LCAT activity and altered cholesterol levels in plasma of full-term and preterm newborn infants. Plasma total, free and esterified cholesterol, total phospholipid and LCAT activity (cholesterol esterified, nmol/ml per h) were determined in placental cord blood. There was a significant negative relationship between total cholesterol levels and gestational age. The increased cholesterol with prematurity was due to both free and esterified cholesterol. There was also a significant negative relationship between LCAT activity and free cholesterol levels but not between LCAT activity and total cholesterol and esterified cholesterol levels. There was no relationship between esterified-to-free cholesterol ratio and LCAT activity. Total phospholipid was not significantly related to either gestational age or LCAT activity. This study suggests that reduced LCAT activity may be one of the factors that result in the accumulation of cholesterol in premature infants. PMID- 1932106 TI - The very-high-density lipoprotein fraction of rabbit plasma is rich in tissue derived cholesterol. AB - When plasma from rabbits, which several weeks earlier had been infused with [3H]cholesterol, was subjected to equilibrium density gradient ultracentrifugation, the specific radioactivity of cholesterol in the very-high density lipoprotein (VHDL) fraction (d 1.22-1.32 g/ml) was three to 8-fold greater (mean, 5.5-fold; P less than 0.001) than that in high-density lipoproteins (HDL; d 1.06-1.21 g/ml). On size exclusion chromatography of plasma, no increase in specific radioactivity was seen in particles smaller than HDL. These findings suggest that those apolipoprotein-lipid complexes that dissociate from HDL during ultracentrifugation to form the VHDL fraction contain proportionately more tissue-derived cholesterol than do those that are more tightly bound to HDL. PMID- 1932107 TI - The role of inverted duplication in the generation of gene amplification in mammalian cells. PMID- 1932108 TI - Interactions of bovine mitochondrial phenylalanyl-tRNA with ribosomes and elongation factors from mitochondria and bacteria. AB - A homologous in vitro poly(U)-directed translation system has been established using animal mitochondrial ribosomes, elongation factors (EF) and phenylalanyl tRNA(Phe). The rate of incorporation of phenylalanine into polyphenylalanine in the mitochondrial system is slower than that observed for the homologous Escherichia coli system. E. coli ribosomes can be used in place of mitochondrial ribosomes in this system with only a slight decrease in the efficiency of phenylalanine incorporation from mitochondrial Phe-tRNA. However, E. coli elongation factor Tu (EF-Tu) cannot replace the mitochondrial EF-Tu in promoting the use of mitochondrial Phe-tRNA. The interaction between EF-Tu and mitochondrial Phe-tRNA was investigated by using the ability of EF-Tu to protect the aminoacyl-tRNA bond from hydrolysis. These results showed that both mitochondrial and E. coli EF-Tus are capable of interacting with mitochondrial Phe-tRNA. However, ribosomal A-site binding assays demonstrated that efficient binding of the mitochondrial Phe-tRNA to the ribosomal A-site was only obtained with the homologous mitochondrial EF-Tu. PMID- 1932109 TI - Expression of the Ku protein during cell proliferation. AB - The Ku protein is a DNA-binding nuclear protein complex composed of 86 kDa and 70 kDa subunits. Recently, in vitro studies suggested a role of the Ku protein in the activation of gene transcription. We studied the expression of these proteins during cell proliferation by Northern blot hybridizations using specific cDNA probes and by immunofluorescence and immunoblot analysis using specific monoclonal antibodies. The genes coding for both subunits were activated during late G1-phase in the transition of human PHA-stimulated lymphocytes from quiescent (G0 phase) to proliferative (S phase) state. These genes were inactivated when human leukemia cells HL60 were differentiated into monocytes upon treatment with the phorbol ester TPA. Changes at the protein level were significantly smaller than changes at the mRNA levels in both cell systems, suggesting a high stability of the Ku protein. Immunofluorescence studies demonstrated nucleolar as well as nuclear localization of the Ku protein in quiescent lymphocytes and during the early G1-phase; during the late G1, S and G2 phases, the Ku protein was only localized in discrete structures in the nucleoplasm. These results demonstrate that the gene expression for the Ku protein is associated with the proliferative state of the cells and that the nucleolar localization of the Ku protein is cell-cycle-dependent. PMID- 1932110 TI - On the translational control of ornithine decarboxylase expression by polyamines. AB - Ornithine decarboxylase (ODC, EC 4.1.1.17) expression is subject to negative feedback regulation by the polyamines. The results of previous studies favor either translational or post-translational regulation. To facilitate further analysis of the mechanism by which polyamines affect ODC expression we have used a cell line (L1210-DFMOr) that overproduces ODC. This cell line was isolated by selection for resistance to the antiproliferative effect of the ODC inhibitor alpha-difluoromethylornithine (DFMO). These cells respond similarly to polyamine depletion and repletion as do their wild-type counterparts. When L1210-DFMOr cells were grown in the presence of 20 mM DFMO (i.e., when their polyamine content was reduced to an extent that still permitted a normal growth rate) ODC represented 4-5% of the soluble protein synthesized. After transfer of the cells to a medium lacking DFMO (i.e., when their polyamine pools were repleted), the rate of incorporation of [35S]methionine into ODC was one order of magnitude lower. Since this difference in incorporation of radioactivity into ODC remained the same irrespective of the pulse-label time used (between 2 and 20 min) it is likely to represent a true difference in ODC synthesis rate. Consequently, the pulse-label experiments cannot be explained by rapid degradation of the enzyme during the labeling period. The difference in ODC synthesis rate was not accompanied by a corresponding difference in the steady-state level of ODC mRNA. Analyses of the distribution of ODC mRNA in polysome profiles did not demonstrate any major difference between cells grown in the absence or presence of DFMO, even though the ODC synthesis rate differed by as much as 10-fold. However, the distribution of the ODC mRNA in the polysome profiles indicated that the message was poorly translated. Thus, most of the ODC mRNA was present in fractions containing ribosomal subunits or monosomes. Inhibition of elongation by cycloheximide treatment resulted in a shift of the ODC mRNA from the region of the gradient containing ribosomal subunits to that containing mono- and polysomes, indicating that most of the ODC mRNA was accessible to translation. Taken together these data lend support to a translational control mechanism which involves both initiation and elongation. PMID- 1932111 TI - Functional analysis of the promoter of the gene encoding the acidic ribosomal protein L45 in yeast. AB - The gene encoding the acidic ribosomal protein L45 in yeast is expressed coordinately with other rp-genes. The promoter region of this gene harbours binding sites for CP1 and ABF1. We demonstrate that the CP1-site is not involved in the transcription activation of the L45-gene. Rather, the ABF1-site, through deviating from the consensus sequence (RTARY3N3ACG), appears to be essential for efficient transcription. Replacement of this site by a consensus RAP1-binding site (an RPG box) did not alter the transcriptional yield of the L45-gene. An additional transcription activating region is present downstream of the ABF1 site. The relevant nucleotide sequence, which is repeated in the L45-gene promoter, gives rise to complex formation with a yeast protein extract in a bandshift assay. The results indicate that the L45-gene promoter has a complex architecture. PMID- 1932112 TI - Regulation of differentially spliced transcripts of acyl-CoA oxidase in the rat. AB - RNAse protection assay was used to distinguish between and to quantify alternatively spliced transcripts of acyl-CoA oxidase in liver, kidney and testis of control and methylclofenapate treated rats. The ratio of spliced transcripts (type I to II) was 1.18:1 in control liver RNA, with 130 and 110 molecules/cell, respectively, and 3.1:1 in treated liver RNA, with 2800 and 900 molecules/cell. The ratios were 1.6 and 2:1 in control and treated kidney, and 0.31:1 in testis. This is likely to be due to differential splicing, which is, therefore, regulated during peroxisome proliferation, and also in a tissue specific fashion. PMID- 1932113 TI - Stable expression of human tissue-type plasminogen activator regulated by beta actin promoter in three human cell lines: HeLa, WI-38 VA13 and KMS-5. AB - A high-level and stable expression system of human tissue-type plasminogen activator (t-PA) was accomplished in human cells by selecting a promoter and a host cell line. First, we have constructed two types of t-PA expression plasmids containing 3 kb of the human beta-actin promoter region or 0.3 kb of SV40 early promoter region and these plasmids were transfected into HeLa cells, respectively, and the resulting transfectants were found to secrete various amounts of t-PA derived from the plasmids to the culture media. Southern blot analysis revealed that the beta-actin promoter was more efficient than the SV40 early promoter with regard to the expression level per single copy of the t-PA gene in the transfected HeLa cells. Next, the t-PA expression plasmid containing the beta-actin promoter was also transfected into WI-38 VA13 cells, a human fibroblastic cell line, and KMS-5 cells, a human lymphoid cell line, in order to compare the expression ability of the promoter among these three cell lines. Some of the transfectants from both cell lines were also found to produce t-PA. It was also found that the expression levels in HeLa and WI-38 VA13 seemed to be more efficient than that in KMS-5. PMID- 1932115 TI - Expression of beta-1,4-galactosyltransferase gene during 3T3 cell growth. AB - The beta-1,4-galactosyltransferase (GT; EC 2.4.1.90) is localized in the trans cisternae of the Golgi apparatus where it catalyzes the transfer of galactose from UDP-galactose to the N-acetylglucosamine residue of secretory and membrane bound glycoproteins. Given the potential role of GT in cell-cell interaction and the fact that numerous cell surface events occur during cell growth we studied the possible relationship between GT expression and 3T3 cell growth. The level of GT mRNA increases 3--4-fold 2 h after serum-stimulation of quiescent 3T3 cells. Protein biosynthesis inhibitors like cycloheximide and anisomycin superinduce GT mRNA expression. Concomitant with this increase is an observed rise in the level of GT protein as well as an increase in overall GT enzymatic activity. Antibody binding studies and direct enzyme assays of intact cells, along with subcellular fractionation experiments indicate that there is an increase in both Golgi and cell surface-associated GT pools upon serum-stimulation of resting cells. We conclude that GT is a member of the cell-cycle dependent genes whose expression is growth regulated. PMID- 1932114 TI - Metallothionein mRNA stability in chicken and mouse cells. AB - Northern blot analysis revealed that metallothionein (MT) mRNAs accumulate after inhibition of protein synthesis with cycloheximide (CHX) in primary cultures of chick embryo hepatocytes and fibroblasts, as well as in an established mouse hepatoma cell line. Inhibition of RNA synthesis with actinomycin D (AMD) led to rapid loss of MT mRNAs in these cells, whereas CHX dramatically retarded the rate of MT mRNA decay (t1/2 greater than 24 h). These results suggest that CHX causes MT mRNA accumulation primarily by increasing stability of MT mRNA. Thus, changes in MT mRNA turn-over rates may play an important role in regulating the accumulation of MT mRNA. The half-lives of MT mRNAs in chicken and mouse cells were determined by oligodeoxyribonucleotide excess solution hybridization with RNA samples extracted after different periods of exposure to AMD. The half-life of chicken MT (cMT) mRNA in uninduced chicken embryo hepatocytes was 3.6 h. Induction of cMT mRNA by pretreatment of these cells with zinc (Zn) prior to exposure to AMD, did not alter the half-life of cMT mRNA significantly. In contrast, cadmium (Cd) induction led to a 2.5-fold increase in the stability of this mRNA. In uninduced chicken embryo fibroblasts, cMT mRNA levels were too low to allow accurate determination of half-life using the methods employed here. However, the half-life of this mRNA in Zn-induced chicken embryo fibroblasts was 6.2 h, whereas it was 9.3 h in Cd-induced cells. Thus, the turn-over rate of cMT mRNA after Cd-induction is very similar in chick embryo fibroblasts and hepatocytes. These data suggest that the accumulation of MT mRNA in chicken cells may reflect, in part, metal-specific effects on MT mRNA stability. The half-lives of mouse MT-I and MT-II (mMT-I and mMT-II) mRNAs in uninduced BNL hepatoma cells were identical (9.2 h), and were not effectively altered after induction by metals (Zn, Cd) or interleukin-1 beta (IL-1 beta). However, mMT mRNAs in pachytene spermatocytes and round spermatids, freshly isolated from the adult testes, were 2.2- to 4.5-fold more stable than in hepatoma cells. These results suggest that cell-type specific accumulation of mMT mRNAs may be regulated, in part, by mRNA stability. PMID- 1932116 TI - Isolation and characterization of the canine thyroglobulin gene promoter region. AB - The 5' flanking sequences from the canine thyroglobulin gene were isolated by homology screening with the evolutionary conserved sequence from the bovine thyroglobulin promoter and sequenced. Transient expression in primary cultured dog thyrocytes demonstrated that the canine clone contains a functional promoter inducible by cAMP. DNAse I footprinting assays showed that the thyroid-specific transcription factor TTF-1, purified from bovine thyroid, also recognizes the canine thyroglobulin promoter. Similar footprints were obtained with crude nuclear extracts from primary cultured dog thyrocytes. PMID- 1932117 TI - Molecular cloning of cell adhesion molecule L1 from human nervous tissue: a comparison of the primary sequences of L1 molecules of different origin. AB - Complementary DNA for the human neural cell adhesion molecule L1 was cloned and sequenced: the deduced amino acid sequence consists of 1257 amino acid residues containing six repeats of the immunoglobulin C2 domain and five repeats of the fibronectin type III domain. The intracellular domain of human L1 is highly conserved as compared to mouse, but not identical to L1 cloned from human melanoma cells, suggesting the existence of alternative forms in the same species. PMID- 1932118 TI - Hem-1, a potential membrane protein, with expression restricted to blood cells. AB - Overlapping cDNAs 3.8 kb in length containing a long open reading frame were obtained that hybridized exclusively to transcripts from hematopoietic cells. Sequence analysis found eight potential membrane domains and two possible cAMP/cGMP phosphorylation sites. This sequence exhibited no homologies with the EMBL/Genbank nucleic acid, SwissProt or GenPept amino acid data bases. The gene is located at 12q13.1, a region of occasional translocations in hematopoietic neoplasia and a rare folic acid fragile site, Fra 12A. PMID- 1932119 TI - Cloning and sequencing of the grass carp (Ctenopharyngodon idellus) growth hormone gene. AB - An enriched lambda gt11 library for screening the grass carp (Ctenopharyngodon idellus) growth hormone gene was constructed using HindIII digested genomic DNA extracted from the spleen of the fish. Probing this library with a homologous cDNA, a clone carrying the growth hormone gene was obtained. The gene is 2501 bp long and consists of five exons and four introns. The sequence of nucleotide in the exons is almost identical to that of the cDNA except for ten positions. Analysis of the 5' sequence up to 1220 bp from the +1 position reveals the presence of a TATA box as well as a number of consensus regulatory sequences. Comparison of the grass carp growth hormone gene with those of other fish indicates that there is a high degree of homology with the gene from the common carp but not with those from the rainbow trout and Atlantic salmon. PMID- 1932120 TI - Molecular cloning of Chinese hamster metallothionein II gene and its 5' flanking region. AB - A genomic DNA clone containing Chinese hamster metallothionein II (MTII) gene and its 5' flanking region was isolated from Cd resistant Chinese hamster ovary (CHO) cells. DNA sequence analysis showed that there are three exons and two introns in the structure of the MTII gene. Further characterization of the 5' flanking region reveals the possible transcription initiation site, metal responsive element and basal-level enhancer sequence. Putatively, this is the promoter region of CHO MTII gene. PMID- 1932121 TI - Characterization of the gene for the bovine seminal vesicle secretory protein SVSP109. AB - As part of an attempt to understand androgen-regulation of SVSP109, a bovine seminal vesicle secretory protein of 109 amino acids, we have characterized the bovine SVSP109 gene. The 6.1 kb gene is organized in five exons and four introns. Regulatory sequences involved in regulation of transcription could not be identified by simple sequence homologies. The SVSP109 gene may provide an excellent example for functional properties of exons: exon 1 encodes the entire signal peptide and exon 4 the complete fibronectin type II-domain, responsible for protein-protein interactions. PMID- 1932122 TI - A variant of glycophorin A resulting from the deletion of exon 4. AB - We have isolated a variant form of glycophorin A which has a 39 bp deletion corresponding to nucleotides 233 to 270 of the coding sequence, which is exon 4 of the glycophorin A gene. The remainder of the sequence is identical to that of the M phenotype of glycophorin A. PMID- 1932123 TI - Rat sperm acrosin: cDNA sequence, derived primary structure and phylogenetic origin. AB - Rat preproacrosin primary structure as predicted from a 1431 nucleotide (nt) cDNA indicates that the molecule is synthesized as a preproenzym consisting of a putative 19 amino acid signal sequence, a 23 amino acid light chain and finally a 395 amino acid heavy chain. Functional domains like the catalytic triad (His-70, Asp-124, Ser-222) are highly conserved not only between the available acrosin primary structures of different mammals but also in comparison with other serine proteinases. Number of amino acid exchanges and the degree in amino acid identity between the different serine proteinases and rat acrosin leads to the assumption that acrosin is one of the early descendants within the phylogenetic tree of the serine proteinase superfamily. PMID- 1932124 TI - Goose-type lysozyme gene of the chicken: sequence, genomic organization and expression reveals major differences to chicken-type lysozyme gene. AB - This report describes the cloning, sequencing and expression pattern of the chicken goose-type lysozyme gene. The cDNA sequence was found to have no homology to that of the chicken-type lysozyme gene and exhibits a completely different exon-intron organization. In addition, goose-type lysozyme displays an overlapping but different tissue expression pattern in chickens than chicken-type lysozyme. PMID- 1932125 TI - Isolation and characterisation of a bovine cDNA encoding eukaryotic initiation factor 2 alpha. AB - Two cDNA clones have been isolated, from a bovine lymphosarcoma library, that encode the alpha-subunit of eukaryotic initiation factor 2 (eIF-2 alpha). The predicted 315 amino acid sequence showed more than 99% amino acid identity with rat and human eIF-2 alpha. Galactose-regulated expression of a full length bovine eIF-2 alpha cDNA in yeast resulted in the synthesis of a polypeptide of the predicted molecular mass (36 kDa). Furthermore, the expressed polypeptide cross reacted with an antibody raised against rabbit eIF-2 alpha confirming the identity of the cDNA. PMID- 1932126 TI - Binding of cathepsin D to the mannose receptor on rat peritoneal macrophages. AB - Adherent cultures of rat peritoneal macrophages secrete lysozyme and the lysosomal marker enzymes beta-glucuronidase, beta-N-acetylglucosaminidase and acid phosphatase; the levels of secreted lysosomal cathepsin D, however, were found to be insignificant. Incubation of the cells at 4 degrees C for 15 min with yeast mannan or with 50 mM mannose, methyl alpha-glucopyranoside, or N acetylglucosamine caused the concentration of cathepsin D in the culture medium to increase 30-40-fold; mannose-6-phosphate had no effect. 125I-labeled cathepsin D was prepared and the binding constant to the macrophage cell surface was determined to be KD = 27 nM. The data suggest that cathepsin D binds to the mannose receptor of macrophages and that binding to this receptor is not in equilibrium with the bulk medium. PMID- 1932127 TI - Effect of carnitine acetyltransferase inhibition on rat hepatocyte metabolism. AB - Carnitine acetyltransferase (CAT) catalyzes the reversible transfer of short chain (less than six carbons in length) acyl groups from acyl-CoA thioesters to form the corresponding acylcarnitines. This reaction has been suggested to be of importance in decreasing cellular content of acyl-CoA under conditions characterized by accumulation of poorly metabolized, potentially toxic acyl-CoAs. To study the importance of the CAT reaction, the effect of CAT inhibitors on rat hepatocyte metabolism in the presence of propionate was examined. Acetyl-DL aminocarnitine inhibited [14C]propionylcarnitine accumulation by isolated hepatocytes incubated with [14C]propionate (1.0-10.0 mM). Inhibition of propionylcarnitine formation by acetyl-DL-aminocarnitine was concentration dependent and was not due to non-specific cellular toxicity as [14C]glucose formation from [14C]propionate, and [1-14C]pyruvate oxidation were unaffected by the CAT inhibitor. Inhibition of propionylcarnitine formation was increased by preincubating hepatocytes with acetyl-DL-aminocarnitine, suggesting competition for cellular uptake between carnitine and the inhibitor. Hemiacetylcartinium (HAC) and meso-2,6-bis(carboxymethyl)4,4-dimethylmorpholinium bromide (CMDM), potent inhibitors of CAT in broken cell systems, did not inhibit hepatocyte propionylcarnitine formation under the conditions evaluated. Propionate (5 mM) inhibited hepatocyte pyruvate (10 mM) oxidation, and this inhibition was partially reversed by 5 mM carnitine. Addition of 5.0 mM acetyl-DL-aminocarnitine abolished the stimulatory effect of carnitine on pyruvate oxidation in the presence of propionate. These studies establish that acetyl-DL-aminocarnitine inhibits intact hepatocyte CAT activity, and thus provide a useful probe of the role of CAT in cellular metabolism. CAT activity appears to be critical for carnitine-mediated reversal of propionate-induced inhibition of pyruvate oxidation. PMID- 1932128 TI - HDL3-retroendocytosis in cultured small intestinal crypt cells: a novel mechanism of cholesterol efflux. AB - The present study in IEC-6 crypt-derived rat epithelial cells describes a retroendocytotic pathway for HDL3. These intestinal cells exhibited specific binding of apoE free HDL3 with a maximal binding capacity of 2980 ng/mg cell protein and a Kd of 36.4 micrograms/ml. Specific binding was competed for by HDL3 but not by LDL. Apparent internalisation of HDL3 was low, degradation was negligible and intact particles were resecreted into the medium within 2 h. Electron microscopic studies showed binding and internalisation of gold-labeled HDL3 in coated pit regions and transport in endosomes distinct from lysosomes to lipid droplets. De novo cholesterol synthesis from [14C]octanoate was enhanced nearly 2-fold by HDL3 and the surplus of newly formed cholesterol was recovered in the medium. It was concluded that intact HDL3 was bound specifically to intestinal cells and was resecreted through a process of retroendocytosis probably mediating efflux of cellular cholesterol. PMID- 1932129 TI - The effects of heparin cofactor II-derived chemotaxins on neutrophil actin conformation and cyclic AMP levels. AB - The serine proteinase inhibitor heparin cofactor II (HC) can be cleaved by polymorphonuclear leukocyte (PMN) elastase (LE) to yield potent chemotactic activity for PMN and monocytes. In contrast to the bacterially-derived chemotaxin formyl-Met-Leu-Phe (fMLP), the HC-derived chemotaxin does not stimulate PMN degranulation or oxidative burst activity. We compared the effects of HC-derived chemotaxins to the effects of fMLP on PMN actin conformation and on the cAMP levels. Both the HC chemotaxins and fMLP rapidly induced an increase in F-actin which was similar in magnitude and time-course. However, in contrast to fMLP, HC derived chemotaxins did not elevate cAMP levels. HC-derived chemotaxins may be useful probes of chemotactic responses, since they do not have the mixed biological activities of fMLP. PMID- 1932130 TI - Chemotactic peptide stimulation of arachidonic acid release in HL60 cells, an interaction between G protein and phospholipase C mediated signal transduction. AB - The mechanism of phospholipase A2 activation by chemotactic peptide was investigated in human promyelocytic HL60 cells. N-Formyl-methionyl-leucyl phenylalanine (fMetLeuPhe) and the non-hydrolyzable GTP analogue guanosine 5' [gamma-thio]triphosphate (GTP[S]) induced arachidonic acid release in permeabilized and metabolically inhibited HL60 cells, a preparation in which calcium was buffered and inositol phospholipid hydrolysis was inhibited. Inositol phosphate generation and arachidonic acid were shown to be temporally dissociated. These results suggest that receptor-dependent phospholipase C activity is not required for fMetLeuPhe to induce arachidonic acid release. However, fMetLeuPhe effects were highly calcium-dependent and inhibition of phospholipase C reduced fMetLeuPhe stimulation of arachidonic acid release even in the permeabilized cell preparation. We conclude that although phospholipase A2 activation is linked to the fMetLeuPhe receptor independent of phospholipase C, actions of phospholipase C to mobilize calcium and release diacylglycerol may be important to phospholipase A2 activation in the intact cell. PMID- 1932131 TI - Glycogen metabolism as detected by in vivo and in vitro 13C-NMR spectroscopy using [1,2-13C2]glucose as substrate. AB - The metabolism of glucose to glycogen in the liver of fasted and well-fed rats was investigated with 13C nuclear magnetic resonance spectroscopy using [1,2 (13)C2]glucose as the main substrate. The unique spectroscopic feature of this molecule is the 13C-13C homonuclear coupling leading to characteristic doublets for the C-1 and C-2 resonances of glucose and its breakdown products as long as the two 13C nuclei remain bonded together. The doublet resonances of [1,2 (13)C2]glucose thus provide an ideal marker to follow the fate of this exogenous substrate through the metabolic pathways. [1,2-(13)C2]Glucose was injected intraperitoneally into anesthetized rats and the in vivo 13C-NMR measurements of the intact animals revealed the transformation of the injected glucose into liver glycogen. Glycogen was extracted from the liver and high resolution 13C-NMR spectra were obtained before and after hydrolysis of glycogen. Intact [1,2 13C2]glucose molecules give rise to doublet resonances, natural abundance [13C]glucose molecules produce singlet resonances. From an analysis of the doublet-to-singlet intensities the following conclusions were derived. (i) In fasted rats virtually 100% of the glycosyl units in glycogen were 13C-NMR visible. In contrast, the 13C-NMR visibility of glycogen decreased to 30-40% in well-fed rats. (ii) In fed rats a minimum of 67 +/- 7% of the exogenous [1,2 (13)C2]glucose was incorporated into the liver glycogen via the direct pathway. No contribution of the indirect pathway could be detected. (iii) In fasted rats externally supplied glucose appeared to be consumed in different metabolic processes and less [1,2-(13)C2]glucose was found to be incorporated into glycogen (13 +/- 1%). However, the observation of [5,6-(13)C2]glucose in liver glycogen provided evidence for the operation of the so-called indirect pathway of glycogen synthesis. The activity of the indirect pathway was at least 9% but not more than 30% of the direct pathway. (vi) The pentose phosphate pathway was of little significance for glucose but became detectable upon injection of [1-(13)C]ribose. PMID- 1932132 TI - Glucocorticoid-receptor binding sites at the 5' flanking region of a rat cytochrome CYP2B2 gene predicted with a novel computer method. AB - Using an original computer method to search for potential DNA binding sites for glucocorticoid-receptor complexes (GRC) (Seledtsov, I.A., Solovjev, V.V. and Merkulova, T.I. (1991) Biochim. Biophys. Acta 1089, 367-376), the presence of two such sites in the 5' flanking region of a rat cytochrome CYP2B2 gene has been predicted. This prediction has been confirmed by gel retardation experiments. PMID- 1932133 TI - Inhibition of platelet aggregation by a fibrinogenase from Naja nigricollis venom is independent of fibrinogen degradation. AB - Fibrinogenases, proteinases which release peptides from the carboxy-terminal end of fibrinogen, are classified as alpha-fibrinogenases or beta-fibrinogenases, based on their ability to preferentially attack the A alpha or B beta chain, respectively, of fibrinogen. alpha-Fibrinogenases have been shown to inhibit platelet aggregation whereas beta-fibrinogenases do not. We have studied the inhibition of platelet aggregation by proteinase F1, an alpha-fibrinogenase from Naja nigricollis venom. This proteinase inhibits whole blood aggregation in a dose-dependent manner, with an IC50 value of 145 micrograms. However, the proteinase fails to inhibit aggregation in washed platelet suspensions. Thus, proteinase F1 appears to require a plasma factor to cause inhibition. Since fibrinogen acts as an adhesive protein which links platelets during aggregation, and since proteinase F1 cleaves fibrinogen, we investigated the role of fibrinogen in the inhibition of platelet aggregation by proteinase F1. The degradation products of fibrinogen formed by the proteinase did not cause significant inhibition. Thus, the inhibition of platelet aggregation appears to be independent of the formation of fibrinogen degradation products. We also studied the effect of proteinase F1 on aggregation of platelets that were reconstituted with defibrinogenated plasma. The proteinase inhibited aggregation of platelets even in the absence of plasma fibrinogen. Proteinase F1 was about 4 fold more potent in inhibiting platelet aggregation in defibrinogenated blood. From these results, we conclude that the inhibition of platelet aggregation by proteinase F1 from N. nigricollis venom is independent of its action on fibrinogen. PMID- 1932134 TI - Basic fibroblast growth factor induces 3T3 fibroblasts to synthesize and secrete a cyclophilin-like protein and beta 2-microglobulin. AB - When stimulated by fibroblast growth factor (FGF) BALB/c 3T3 cells synthesize and secrete elevated amounts of five proteins called the 'superinducible proteins', or SIPs. The expression of these proteins is greatly enhanced if the cells are treated with cycloheximide during induction. The 24 kDa protein (SIP24) has been purified and antiserum raised against it. This protein is N-glycosylated and probably structurally constrained by one or more intramolecular disulfide bonds. The amino acid sequences of three of four peptides show significant identity with cyclophilin, an abundant cytoplasmic protein believed to mediate the immunosuppressive effects of cyclosporin A. Several members of the cyclophilin family have been identified, and cDNA clones of two cyclophilin-like proteins with signal sequences have been reported. Here we show that at least one cyclophilin-like protein is secreted and that its expression is regulated by growth factors. The 12.5 kDa protein (SIP12.5) was found to be immunoprecipitated by an antiserum raised to human beta 2-microglobulin. This protein is strongly induced by interferon, which is a characteristic of the beta 2-microglobulin gene. Thus, FGF stimulates mouse embryo 3T3 cells to produce two proteins related to immune regulatory molecules. This may reflect an interaction between immune cells and nonimmune cells that occurs in vivo during processes such as wound healing when growth factors are released locally. PMID- 1932135 TI - Vasopressin stimulates pyruvate utilization through a Ca(2+)-dependent mechanism and lactate formation by a protein kinase C-dependent mechanism in isolated rat hepatocytes. AB - Vasopressin stimulates lactate production by hepatocytes from fed rats, an effect which has been attributed exclusively to Ca2+ activation of glycogenolysis. We provide evidence here for two further actions of vasopressin which affect lactate formation by rat hepatocytes. In the presence of 50 mM glucose, vasopressin inhibited lactate production by hepatocytes. The inhibition was relieved by the presence of alpha-cyano-4-hydroxycinnamate (alpha-CHC), which blocks mitochondrial pyruvate transport. This suggests that vasopressin stimulates pyruvate utilization in the presence of a high concentration of glucose. Epidermal growth factor (EGF), which also increases lactate formation by hepatocytes, did not similarly decrease lactate accumulation in the presence of high glucose, suggesting no stimulation of lactate and pyruvate utilization by this hormone. In cells depleted of Ca2+, vasopressin also stimulated lactate formation. Although vasopressin did not cause the apparent translocation of protein kinase C between cell spaces, phospholipase C treatment of hepatocytes did duplicate vasopressin stimulation of lactate formation, provided fatty acid oxidation was suppressed by the simultaneous presence of the inhibitor palmixorate. We conclude that three actions of vasopressin affect lactate and pyruvate formation: the calcium-linked activations of glycogenolysis and mitochondrial pyruvate utilization, and a stimulation of glycolysis likely mediated by protein kinase C. PMID- 1932136 TI - Hepatocyte conditioned medium modulates the response of primary rat hepatocyte cultures to epidermal growth factor. AB - Primary hepatocytes may produce autocrine growth trigger(s) with or without a mitogenic stimulus. We explored the potential of hepatocyte conditioned medium- from untreated quiescent cultures--to modulate the DNA synthetic responses induced by EGF. The EGF-induced responses were similar when EGF was continuously or transiently (3 h) present. Conditioned medium (CM) from 48 h hepatocyte culture was the most effective in eliciting thymidine incorporation into hepatocyte DNA. At the same time the conditioned medium from hepatocyte cultures stimulated lymphocyte DNA synthesis at levels much lower than those observed using PHA, a specific lymphocyte inducer. The maximal EGF-binding by intact hepatocytes was also significantly increased in the presence of conditioned medium (48 h). We therefore suggest that hepatocytes produce autocrine growth trigger(s) which might be in part responsible for the regulation of the in vitro and/or in vivo hepatocyte proliferation. PMID- 1932137 TI - Activation of protein kinase C is not required for glyceraldehyde-stimulated insulin secretion from rat islets. AB - Glyceraldehyde-induced insulin release from rat islets of Langerhans was not affected following down-regulation of protein kinase C (PKC) by prolonged exposure to the tumour-promoting phorbol ester, 4 beta-phorbol myristate acetate (PMA). Glyceraldehyde did not cause translocation of islet PKC under conditions in which PMA stimulated redistribution of enzyme activity. These results indicate that activation of PKC is not required for glyceraldehyde stimulation of insulin secretion from normal rat islets. PMID- 1932138 TI - Cytokine production by cholesterol-loaded human peripheral monocyte-macrophages: the effect on fibrinogen mRNA levels in a hepatoma cell-line (HepG2). AB - Conditioned medium from human monocyte-macrophages incubated under various conditions was tested for its ability to stimulate fibrinogen mRNA levels in the hepatoma cell line HepG2. Recombinant human interleukin-6 (IL-6) stimulated fibrinogen mRNA levels 4.4-fold over control levels; this response was blocked by an anti-IL-6 antibody. Conditioned medium from 3-day-cultured monocyte macrophages produced a slight stimulation of fibrinogen synthesis in HepG2 cells which was enhanced when the monocyte-macrophages had been treated with lipopolysaccharide (LPS). This stimulation was blocked by the anti IL-6 antibody. The cytokines, interleukin-1 (IL-1) and tumour necrosis factor (TNF) were also detected in the conditioned medium from the 3-day-cultured monocyte-macrophages. Monocyte-macrophages were cultured for 17 days and then incubated with acetylated low density lipoprotein (AcLDL) for 48 h. Such cells were 'foamy' in appearance and showed a 4-fold increase in apoE mRNA and a 10 to 50-fold increase in apoE secretion. This increase in apoE production was suppressed by almost a third when cells were coincubated with AcLDL and LPS. Conditioned medium from these 17-day cultured AcLDL-treated human monocyte-macrophages did not stimulate fibrinogen mRNA synthesis in HepG2 cells, nor did the conditioned medium contain detectable levels of cytokines. These results suggest that cytokine production from foam cells in the atherosclerotic lesion is unlikely to be a major contributing factor in determining the elevated fibrinogen levels seen in the plasma of patients with IHD. PMID- 1932139 TI - Glucocorticoid-mediated muscle atrophy: alterations in transcriptional activity of skeletal muscle nuclei. AB - Glucocorticoid-induced muscle atrophy is associated with a decrease in the level of protein synthesis and a loss of RNA. This paper reports the behaviour of RNA polymerase I- and RNA polymerase II-directed transcription (EC 2.7.7.6) in nuclei isolated from skeletal muscles of rats given a catabolic dose of dexamethasone acetate (5 mg per Kg body weight) over a period of 4 days. Both activities were altered by the dexamethasone treatment. In the case of RNA polymerase I-mediated transcription there was a loss of template-engaged enzymes indicating the existence of an inhibition of initiation of transcription while the rate of elongation of bound enzymes was unaltered. The number of RNA polymerase II chromatin bound enzymes was increased, but the mean polynucleotide elongation rate was reduced. The possibility that glucocorticoids may impair the elongation stage of transcription in skeletal muscle by increasing the frequency of premature termination of transcripts is discussed. No evidence was obtained for any increase in ribonuclease activity in muscle nuclei of dexamethasone-treated animals. PMID- 1932140 TI - Studies on the mechanism of Salmonella typhimurium enterotoxin-induced diarrhoea. AB - The unidirectional fluxes of Na+ and Cl- were studied in Salmonella typhimurium enterotoxin-treated rats. There was net secretion of Na+ and Cl- in toxin-treated animals, while in control animals there was net absorption of these ions. In the presence of the Ca(2+)-ionophore, there was net secretion of Na+ and Cl- in the control group, while the ionophore enhanced the secretion of these ions in experimental animals. The calcium channel blocker, verapamil, decreased the secretion induced by salmonella toxin, but could not reverse the secretion to absorption. There was no difference in the net absorption of Ca2+ in both the control and experimental animals. There was a significant increase in the intracellular free calcium concentrations in enterocytes isolated from toxin treated rat intestines as compared to that in enterocytes isolated from control animals. In the presence of PMA (phorbol-12-myristated-13-acetate) there was net secretion of Na+ and Cl- in the control group, while in the experimental group there was no change in the fluxes of these ions. The selective, potent inhibitor of protein kinase C, H-7 (1-(5-isoquinolinylsulphonyl)-2-methylpiperazine) reversed the secretion of Na+ and Cl- in the toxin-treated group to absorption. The addition of indomethacin also inhibited the secretion induced by salmonella toxin, but failed to reverse it to absorption. However, the addition both H-7 and indomethacin to the experimental group had a partial additive effect. These studies demonstrate that the Salmonella enterotoxin-mediated fluid secretion involves protein kinase C and the arachidonic acid metabolites and perhaps does not involve the extracellular calcium pools. PMID- 1932141 TI - Amino acid sequence of k Sci, the Bence Jones protein isolated from a patient with light chain deposition disease. AB - Light chain Sci was isolated from the urine of a patient affected by light chain deposition disease with an apparent exclusive localization to the kidney. Sci protein is an intact light chain: it consists of 214 amino acid residues and has an Mr of 23.65. Its complete primary structure has been determined by sequence analysis of the corresponding tryptic peptides and by partially sequencing the intact protein. Sequence comparison shows that Sci protein is strictly related to the light chains of kIIIa family (88% structural identity) which are usually expressed in autoimmune rheumatoid syndromes. Computer graphics model suggests a perturbation in k Sci three-dimensional structure due to the unusual replacement of residues 53 and 77. PMID- 1932142 TI - A second transthyretin mutation at position 33 (Leu/Phe) associated with familial amyloidotic polyneuropathy. AB - Genomic DNA was isolated from peripheral blood lymphocytes of a patient with familial amyloidotic polyneuropathy (FAP) and the transthyretin (TTR) gene examined for sequence mutations. Polymerase chain reaction was used to asymmetrically amplify the TTR exons. Direct DNA sequencing of the PCR product revealed a C for T mutation at the first base of codon 33 located in exon 2 of one transthyretin gene. This resulted in a substitution of leucine for phenylalanine at position 33. Exons 3 and 4 were examined and found to be normal. The mutation creates a novel DdeI restriction site at the point of the mutation. PMID- 1932143 TI - Age-dependent expression of cytochrome P-450s in rat liver. AB - Age-related changes in the levels of multiple forms of cytochrome P-450 as well as in the testosterone hydroxylation activities of hepatic microsomes of male and female rats of different ages from 1 week to 104 weeks (24 months) were investigated. The total cytochrome P-450 measured photometrically did not change much with age in either male and female rats. Testosterone 2 alpha-, 2 beta-, 6 beta-, 15 alpha-, 16 beta-hydroxylation activities of male rats were much higher than those in female rats and were induced developmentally. These activities in male rats declined with aging to the very low level in female rats by 104 weeks of age. Testosterone 7 alpha-hydroxylation activity was maximum at 3 weeks of age in rats of both sexes. The levels of individual cytochrome P-450s were measured by immunoblotting. P450IA1 and IA2 (3-methylcholanthrene-inducible forms) and P450IIB1 and IIB2 (phenobarbital-inducible forms) were detected at low levels in rats of both sexes at all ages. P450IIA2, IIC11 and IVA2 were detected in male rats only and were induced developmentally. These male-specific forms disappeared in male rat liver at 104 weeks of age. P450IIC12, a typical female-specific form, was induced developmentally in female rats and was also detected in male rats at 3 and 104 weeks of age. P450IIIA2 (testosterone 6 beta-hydroxylase) was induced developmentally in male rats, but disappeared when the rats were 104 weeks of age. In female rats, P450IIIA2 was detected only at 1 and 3 weeks of age. P450IIA1, IIC6, IIE1 and IVA3 were detected in rats of both sexes at any age. P450IIC6 and IVA3 were induced developmentally and detected at a similar level in rats of both sexes. The level of P450IIA1 was maximum at 3 weeks of age in rats of both sexes. The changes in the level of P450IIE1 during aging were small compared with the changes in other cytochrome P-450s used in this study. These observations provide concrete evidence to our earlier hypothesis that each of the forms of cytochrome P-450 in male rats alter with aging in different patterns resulting in a practical feminization of over-all cytochrome P-450 composition at old age. PMID- 1932144 TI - Determination of G-protein levels, ADP-ribosylation by cholera and pertussis toxins and the regulation of adenylyl cyclase activity in liver plasma membranes from lean and genetically diabetic (db/db) mice. AB - Liver plasma membranes prepared from genetically diabetic (db/db) mice expressed levels of Gi alpha-2, Gi alpha-3 and G-protein beta-subunits that were reduced by some 75, 63 and 73% compared with levels seen in membranes from lean animals. In contrast, there were no significant differences in the expression of the 42 and 45 kDa forms of Gs alpha-subunits. Pertussis toxin-catalysed ADP-ribosylation of membranes from lean animals identified a single 41 kDa band whose labelling was reduced by some 86% in membranes from diabetic animals. Cholera toxin-catalysed ADP-ribosylation identified two forms of Gs alpha-subunits whose labelling was about 4-fold greater in membranes from diabetic animals compared with those from lean animals. Maximal stimulations of adenylyl cyclase activity by forskolin (100 microM), GTP (100 microM), p[NH]ppG (100 microM), NaF (10 mM) and glucagon (10 microM) were similar in membranes from lean and diabetic animals, whereas stimulation by isoprenaline (100 microM) was lower by about 22%. Lower concentrations (EC50-60 nM) of p[NH]ppG were needed to activate adenylyl cyclase in membranes from diabetic animals compared to those from lean animals (EC50-158 nM). As well as causing activation, p[NH]ppG was capable of eliciting a pertussis toxin-sensitive inhibitory effect upon forskolin-stimulated adenylyl cyclase activity in membranes from both lean and diabetic animals. However, maximal inhibition of adenylyl cyclase activity in membranes from diabetic animals was reduced to around 60% of that found using membranes from lean animals. Pertussis toxin-treatment in vivo enhanced maximal stimulation of adenylyl cyclase by glucagon, isoprenaline and p[NH]ppG through a process suggested to be mediated by the abolition of functional Gi activity. The lower levels of expression of G protein beta-subunits, in membranes from diabetic compared with lean animals, is suggested to perturb the equilibria between holomeric and dissociated G-protein subunits. We suggest that this may explain both the enhanced sensitivity of adenylyl cyclase to stimulation by p[NH]ppG in membranes from diabetic animals and the altered ability of pertussis and cholera toxins to catalyse the ADP ribosylation of G-proteins in membranes from these two animals. PMID- 1932145 TI - The effect of vitamin E analogues and long hydrocarbon chain compounds on calcium induced muscle damage. A novel role for alpha-tocopherol? AB - Previous studies have demonstrated that supplemental alpha-tocopherol inhibited calcium-induced cytosolic enzyme efflux from normal rat skeletal muscles incubated in vitro and suggested that the protective action was mediated by the phytyl chain of alpha-tocopherol [1]. In order to investigate this further a number of hydrocarbon chain analogues of tocopherol (7,8-dimethyl tocol, 5,7 dimethyl tocol, tocol, alpha-tocotrienol, alpha-tocopherol [10], vitamin K1, vitamin K1 [10], vitamin K1 diacetate, vitamin K2 [20], phytyl ubiquinone and retinol) were tested for any ability to inhibit calcium ionophore, A23187, induced creatine kinase (CK) enzyme efflux. Some compounds were found to be very effective inhibitors and comparison of their structures and ability to inhibit TBARS production in muscle homogenates revealed that the effects did not appear related to antioxidant capacity or chromanol methyl groups, but rather the length and structure of the hydrocarbon chain was the important mediator of the effects seen. PMID- 1932146 TI - An outward-rectifying potassium channel in primary cultures of sweat glands from cystic fibrosis subjects. AB - We have previously described a high conductance calcium-activated 'maxi K' channel in primary cultures of human eccrine sweat gland cells both from normal subjects and those with cystic fibrosis. In further studies we have now identified a potassium-selective channel of much lower conductance which shows outward-rectification and which is present in sweat glands isolated from cystic fibrosis subjects. In experiments with inside-out patches using symmetrical pipette and bath solutions containing 140 mM K+ the channel showed an outward slope conductance (at +50 mV) of approximately 26 pS and an inward conductance (at -50 mV) of approximately 11 pS. When K+ in the bath was replaced by Na+ the reversal potential shifts to reveal a permeability ratio PK/PNa approximately 40 Unlike the maxi-K+ channel, the outward-rectifying channel does not show sensitivity to Ca2+. Channels were found in cells cultured from the glands of four out of five cystic fibrosis subjects. In cells cultured from 30 subjects who did not have cystic fibrosis, an outward-rectifying potassium channel was seen in only one out of approximately 3000 patches. PMID- 1932147 TI - A new mtDNA mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). AB - In 3 of 40 MELAS patients, a new common mutation, a T-to-C transition at nucleotide position 3271 in the mitochondrial tRNA(Leu(UUR] gene was recognized and was very near to the most common mutation site at 3243. With a simple detection method using polymerase chain reaction with a mismatch primer, none of 46 patients with other mitochondrial diseases and 50 controls had this mutation. PMID- 1932148 TI - Buprenorphine and cocaine addiction: the need for caution. PMID- 1932149 TI - Sexual behaviors and HIV infection in intravenous drug users in New York City. AB - Heterosexual transmission of HIV infection is closely linked with intravenous drug use. This study investigated the sexual behaviors of intravenous drug users (IVDUs) in New York City. In 1986, 284 IVDUs were recruited from newly enrolled patients in methadone treatment clinics. A questionnaire asking for information on sexual behaviors was administered and sera were collected and tested by ELISA and Western Blot techniques. Associations between behavioral data and HIV serology were evaluated using univariate methods of analysis. HIV infection was significantly associated with age (p = 0.01). Subjects not claiming prostitution were also significantly more likely to be infected (p = 0.01). Subjects reporting condom use and oral sex had lower infectivity rates. Higher infection rates were observed in subjects reporting anal sex and homosexual or bisexual sexual behavior. The findings of this study suggest that greater efforts to isolate those sexual behaviors that are predictors or correlates of heterosexual transmission of HIV infection is much needed in order to design behavioral interventions that will effectively curtail the spread of this virus. PMID- 1932150 TI - Drinking experiences in three populations of male drinkers. AB - The first drinking experience has been suggested as an important point in etiological processes associated with alcohol use and abuse. In this study, initial drinking experiences were assessed among populations of alcoholics, problem drinkers, and non-problem drinkers. Results showed that the alcoholics and problem drinkers more frequently consumed 5 or more drinks during their initial drinking occasion than the nonproblem drinkers. Alcoholics were most likely to experience their second drinking event within several days. In addition, there was a tendency for alcoholics and problem drinkers to describe more negative effects associated with their initial drinking experience. No effects were found for age of first drink or its location. Such differences in first drinking may have implications for understanding the etiology of drinking problems. PMID- 1932151 TI - Effect of gender on neurologic findings in alcoholics. AB - We examined 340 men and 60 women admitted for alcohol detoxification to determine if there was a difference in the neurologic effects of alcohol on men and women with similar alcohol, drug, and medical histories. Focal neurologic deficits, seizure histories, and electroencephalographic abnormalities were assessed. Confounding factors, such as illicit drug use, head trauma, neurosurgery, and repeated detoxifications were monitored in both male and female populations. Our findings reveal no excess focal neurologic deficits in women compared to men. EEG recordings revealed more abnormalities in women than men, but there was no excess seizure activity reported for the women. For men, the prevalence of seizure histories is correlated with the number of inpatient detoxifications to which the patient submitted. For women, the correlation of seizure prevalence with detoxification admissions does not hold. PMID- 1932152 TI - Suicide risk associated with drug and alcohol dependence. AB - The association of alcohol and drugs with suicidal thinking and behavior is both causal and conductive. The subjective state of hopelessness is key to the disposition to actual suicides. Alcohol and drugs are influential in providing a feeling of hopelessness by their toxic effects, by possible manipulating of neurotransmitters responsible for the mood and judgement and by disruption of interpersonal relationships and social supports. The identification of alcohol and drug use and dependence is critical to the proper assessment of suicide. According to studies, over fifty percent of all suicides are associated with alcohol and drug dependence and at least 25% of alcoholics and drug addicts commit suicide. Over 70% of adolescent suicides may be complicated by drug and alcohol use and dependence. Because alcoholism and drug addiction are leading risk factors for suicidal behavior and suicide, any alcoholic or drug addict should be assessed for suicide, especially if actively using alcohol or drugs. PMID- 1932153 TI - The use of buprenorphine and temazepam by drug injectors. AB - There has been concern over the growing misuse of buprenorphine and temazepam in Scotland. In interviews with 78 clients of Glasgow drug agencies during 1989 1990, it was found that buprenorphine and temazepam are now more widely and frequently misused than heroin or other opiates. Fifty-eight percent of buprenorphine users used six to seven days weekly. Fewer users of other drugs used as frequently. Heroin, other opiates and temazepam were associated with criminality. Buprenorphine, perhaps because it is relatively inexpensive, was not associated with criminality. Implications for drug policy and treatment are discussed. PMID- 1932154 TI - Cognitive processes and cognitive behavior therapy in the treatment of problem drinking. AB - Cognitive behavior Therapy has been shown to be an effective therapy for a wide range of clinical problems. However, the efficacy of CBT on addictive behavior is still unknown. This paper reviews the evidence for the efficacy of cognitive behavior therapy treatment for problem drinkers and examines its relationship with cognitive models of problem drinking. A computer search of the literature showed that only 13 studies met the criteria for inclusion in this review. This review indicated that there is evidence to show that cognitive behavior therapy can be successfully applied to addictive behaviors, in particular, problem drinking. However, there is lack of evidence to show that cognitive behavior therapy supports cognitive models of problem drinking. Future direction for research in this area is suggested. PMID- 1932155 TI - Determination of MK-287, a new platelet-activating factor antagonist, in plasma and serum by gas chromatography chemical ionization mass spectrometry. AB - MK-287 is a novel platelet-activating factor antagonist. A sensitive and specific gas chromatographic/mass spectrometric assay has been developed for the determination of the drug in serum and plasma. The assay utilizes an extraction with methyl-t-butyl ether and subsequent trimethylsilylation of the hydroxyl function. The gas chromatographic/mass spectrometric determinations are carried out with temperature-programmed capillary gas chromatography and ammonia negative chemical ionization mass spectrometry. The method has sufficient sensitivity, precision, accuracy and selectivity for the analysis of drug concentrations in clinical samples. PMID- 1932156 TI - Stable isotope dilution method for the determination of serum glucose using discharge-assisted thermospray liquid chromatography/mass spectrometry. AB - A discharge-assisted thermospray liquid chromatography/mass spectrometric method for the determination of serum glucose was studied. Isotope dilution technique was used with uniformly labelled (13C6) glucose as an internal standard. Successful liquid chromatography/mass spectrometry was achieved by post-column addition of aqueous ammonium acetate to the mobile phase. Quantification was performed by measuring the peak intensity ratios of the unlabelled and labelled [M + NH4]+ ions. Analytical results using the National Institute of Standards and Technology standard reference material serum showed satisfactory agreement with the certified value, and a relative standard deviation of about 1% was obtained. PMID- 1932157 TI - Derivatization of peptides to enhance ionization efficiency and control fragmentation during analysis by fast atom bombardment tandem mass spectrometry. AB - Novel and simple procedures for preparing ethyl-triphenylphosphonium derivatives of peptides are described. These procedures allow an ethyl-triphenylphosphonium moiety to be selectively attached to either the N- or C-terminus. The resulting derivatives contain a positive charge at a fixed position and have significant hydrophobic character. Modification of peptides by these chemical methods significantly enhances the efficiency of fast atom bombardment ionization, especially of hydrophilic peptides. Moreover, upon collisionally activated dissociation, the derivatized peptides generate a predictable series of sequence ions from either the C-terminus or the N-terminus, depending on the location of the ethyl-triphenylphosphonium moiety. PMID- 1932158 TI - Determination of diclofenac in human plasma by selected ion monitoring. AB - A simple and rapid gas chromatographic/mass spectrometric method to determine plasma diclofenac was developed, which employs formation of the methyl ester with diazomethane. Methoxydiclofenac was used as the internal standard. Under the conditions used, the previously described partial cyclization of diclofenac to the indolone derivative was avoided. The limit of detection of plasma levels of diclofenac is 2 ng ml-1, which renders the method useful for clinical studies on oral, intravenous and rectal administration of the drug. The analysis is carried out by electron impact gas chromatography/mass spectrometry and can therefore be performed on the more common mass spectrometers. Linearity and reproducibility of the method were demonstrated by the high correlation coefficient of the calibration lines (r greater than 0.999) and from the low variation of their slopes (coefficient of variation 3%) determined on different days, respectively. Pharmacokinetic parameters (area under curve = 1.8 +/- 0.26 microgram h ml-1, tmax = 1.5 +/- 0.5 h, Cmax = 734 +/- 82 ng ml-1 and terminal half-life = 0.88 +/- 0.52 h) determined from the plasma decay of diclofenac in three healthy subjects given a single oral dose of diclofenac were in good agreement with those reported in the literature. PMID- 1932159 TI - Incorporation of tandem mass spectrometric detection to the analysis of peptide mixtures by continuous flow fast atom bombardment mass spectrometry. AB - The ability to acquire structurally informative daughter ion spectra for individual peptides undergoing separation and analysis by continuous flow fast atom bombardment (CF FAB) is demonstrated. To illustrate the potential of this methodology, tryptic and chymotryptic digests of the 29-residue peptide glucagon were analyzed by CF FAB using mass spectrometric and tandem mass spectrometric detection in consecutive analyses. Daughter ion spectra were recorded using B/E linked scans for the major hydrolysis products observed by liquid chromatography/mass spectrometry. The peptide mixtures were separated by gradient capillary high-performance liquid chromatography with the FAB matrix being added post-column using a coaxial flow interface between the column and flow probe. The entire effluent (3 microl min(-1)) was sampled by the mass spectrometer. Results obtained using less than 300 pmol of digested glucagon indicated several advantages to tandem mass spectrometric detection including the ability to confirm identities for products of enzymatic digestion and the potential use of this method for tandem sequence analysis of peptide mixtures. PMID- 1932161 TI - Inpatient education for fiberoptic/videoptic diagnostic and therapeutic procedures for gastroenterology. AB - The purpose of this study was to evaluate the educational needs of the inpatient undergoing gastroenterology or pulmonary diagnostics or therapeutics using fiberoptic or videoptic technology. This study provided a mechanism to increase nursing, patient and family understanding of fiberoptic/videoptics diagnostics and treatment modalities. Interviews and surveys were used to evaluate the educational preparation of inpatients. These data revealed a significant difference in the educational preparation of inpatients compared to outpatients, which was a concern for quality standards in the preparation of gastroenterology/bronchoscopy patients. Teaching methods and tools were implemented in the inpatient environment with a measurable increase in patient preparation for gastroenterology/bronchoscopy procedures. This article will outline the findings, implementation methods and outcomes reported in a procedural gastroenterology laboratory performing approximately 2,000 procedures per year. PMID- 1932160 TI - Care of the diabetic patient who is NPO for a procedure. AB - Nursing care of the diabetic patient who is NPO for a procedure presents many challenges. Unwise treatment and care decisions may be made because of misunderstanding about the body's basal need for insulin. "Hold-the-insulin" routines are dangerous. Guidelines for management of these patients can provide the necessary information and confidence for excellent nursing care. PMID- 1932162 TI - Certification update. PMID- 1932163 TI - Infection control practices in gastrointestinal endoscopy in the United States: a national survey. AB - OBJECTIVE: To ascertain current infection control practices, endoscope cleaning procedures, perceived risks of infection, and implementation of universal precautions in gastrointestinal endoscopy units in the United States. DESIGN: National mailed survey of gastroenterology nurses and associates conducted anonymously in March 1988. SETTING: Completed surveys were received from all 50 states and Puerto Rico and from all practice settings. The most common practice setting was private/community hospitals (66%). PARTICIPANTS: Of the 4,952 survey forms mailed to all members and to interested nonmembers of the Society of Gastrointestinal Nurses and Associates, 2, 158 (44%) were returned and 2,030 (41%) were completed and evaluable. Of the respondents, 1,487 (73%) were registered nurses. RESULTS: Sixty-seven percent (n = 1,358) of the respondents routinely used an enzymatic cleaner as a step in the instrument decontamination process; 93% (n = 1,879) chemically disinfected instruments after each case; and 88% (n = 1,779) disinfected endoscopes with an aqueous glutaraldehyde product. Respondents reported that they and a significantly smaller proportion of physicians (p less than .001) employed barrier precautions for all endoscopic cases involving possible contact with blood/body fluids of patients known (66% versus 57%, respectively) and not known (12% versus 8%, respectively) to have a bloodborne infection. Endoscopy-related infections, usually bacterial, were reported to have occurred at their institutions by 6% (n = 116) of respondents. CONCLUSIONS: We conclude that cleaning, disinfection, and sterilization procedures for gastrointestinal endoscopic instruments vary, that appropriate protective apparel is not always worn, and that some practices may lead to preventable endoscopy-related infection in patients. PMID- 1932164 TI - Transbronchial needle aspiration. AB - Transbronchial needle aspiration biopsy is an endoscopic pulmonary procedure used to diagnose a variety of pulmonary conditions including staging patients with lung cancer and identifying nodules, masses, and benign disorders such as sarcoidosis. Transbronchial needle aspiration biopsy is a safe procedure, performed primarily with local anesthesia combined with intravenous sedation. With the anticipation of this procedure being widely used, more endoscopy nurses will be exposed to this technique. This article is intended to educate nurses and technicians about the procedure of transbronchial needle aspiration and its instruments. PMID- 1932165 TI - Helpful hints for endoscopic biliary stenting. AB - At Duke University Medical Center approximately 1,000 endoscopic retrograde cholangiopancreatography procedures are completed per year. Hints for biliary stenting have been developed. This article is meant to provide the GI nurse/associate with a quick reference when assisting with stent placement. PMID- 1932166 TI - The GI clinical nurse specialist: a generic role delineation. SGNA Masters Prepared Special Interest Group. AB - We may have a role but find it difficult to specifically define it. As various specialties have emerged, roles have developed based on patient or physician need or practitioner innovation. This article is an attempt to present an organized structure of the contribution that can be made by the masters prepared gastroenterology nurse. PMID- 1932167 TI - Defecography as part of the evaluation of anorectal dysfunction. AB - Defecography is the evaluation of the anus and rectum during the act of defecation. We have devised a very simple method of performing this examination in conjunction with the Radiology Department. The entire procedure takes less than 15 minutes from start to finish. In our hospital, we have performed over 130 of these tests. A high level of patient cooperation has been noted in our experience. For the most part, the entire procedure from bowel preparation to final films is well tolerated. PMID- 1932168 TI - Kinevac (sincalide for injection)/Squibb Diagnostics. AB - Sincalide is a rapid-acting, synthetic analog of cholecystokinin for intravenous use in postevacuation cholecystography. Serious reactions to sincalide have not been reported. The intravenous administration of sincalide causes a prompt contraction of the gallbladder as compared to the stimulus of a fatty meal which causes progressive contraction that becomes maximal in about 40 minutes. The use of Kinevac to accelerate the transit time through the small bowel decreases the time and extent of radiation associated with fluoroscopy and length of the x-ray examination of the intestinal tract. Duodenal aspiration obtained after the administration of Kinevac provides a sample of concentrated bile for analysis of cholesterol, bile salts, phospholipids and crystals. When used in conjunction with secretin to stimulate pancreatic secretion, an aspirate is readily obtained for analysis of enzyme activity, composition and cytology. As the development of endoscopic manometry affords a modality to measure and record sphincter of Oddi pressures, the paradoxical responses noted to the intravenous administration of CCK during manometric evaluation supports the diagnostic value of Kinevac used as a provocative agent in the evaluation of biliary dyskinesia. PMID- 1932169 TI - Cycles in the evolution of a nuclear medicine journal. PMID- 1932170 TI - Reversibility of complete unperfusion in a patient with recurrent hemoptysis. AB - We present a case of a 68-year-old woman with a history of mild smoking and chronic bronchitis who showed recurrent hemoptysis. She presented with a nearly normal chest roentgenogram, a non-diagnostic fiberoptic bronchoscopy and a computed tomography and lung scanning both of which were highly suggestive for malignancy. In fact, the former showed obstruction of the main left bronchus, of the superior bronchus for the left upper lobe and of the apical bronchus for the left lower lobe, the latter showed a total cessation of blood flow through the left lung. Pulmonary angiography, however, was normal and aortography showed dilatated and twisted left bronchial arteries. Computed tomography and lung scanning came back to normal after bronchoscopic aspiration of endobronchial clots and a nonspecific antibiotic therapy were carried out. Although very infrequent, bronchial stenosis on CT and complete monolateral unperfusion on lung scintigraphy may occur in patients with hemoptysis of benign origin. We recommend the use of pulmonary arteriography in patients with the above pattern when diagnostic doubt remains after bronchoscopy. PMID- 1932171 TI - 99mTc-human immunoglobulin (HIG) in AIDS patients: first results. AB - Scintigraphy with 99mTc labelled human polyclonal immunoglobulin was performed in 16 patients with ascertained or suspected AIDS-related infections. 99mTc-HIG lung scanning was compared, in 11 patients, with 67Ga scintigraphy, chest X-ray and high resolution lung CT. 67Ga and 99mTc-HIG were concordantly positive in five cases of BAL-ascertained Pneumocystis carinii pneumonia (PCP), while one of them was Rx and CT negative. X-ray, 67Ga and 99mTc were concordantly negative in 5 cases. 99mTc-HIG yielded negative results in two cases of Mycobacterium infection, both of which were 67Ga and Rx positive: Mycobacterium avium in diffuse lung involvement and Mycobacterium TBC in excavated infiltrate. 99mTc-HIG was also positive in other 3 AIDS patients: 1 case of intestinal cryptosporidiosis, 1 pulmonary abscess (Staphylococcus and Candida), and 1 sacral abscess; it was negative in 1 case of Kaposi sarcoma (also 201Tl negative). In conclusion, 99mTc-HIG scintigraphy in AIDS patients is feasible, and offers some practical advantages (continuous availability, fast response time, etc.). The initial results seem similar to those of 67Ga in lung scanning (and perhaps more specific for PCP). PMID- 1932172 TI - Immunoscintigraphy with radiolabeled antibodies: an overview of the progress and limitations. PMID- 1932173 TI - Analytical and clinical assessment of a commercial kit for the simultaneous determination of free thyroxine and thyrotropin. AB - The SimulTRAC FT4/TSH kit (Becton Dickinson), allowing a simultaneous determination of free thyroxine (FT4) and thyrotropin (TSH), was assessed in terms of analytical quality and clinical performance. The results of a multicenter trial were included in this study to obtain a more complete and reliable information. The current validation procedures (ie evaluation of analytical imprecision and sensitivity, between-kit comparison of estimates and- limited to TSH--check of response linearity on dilution) demonstrated quite acceptable analytical characteristics for both the FT4 and the TSH tests. The diagnostic sensitivity and predictive value were derived for separate and combined tests from a relatively large number of cases (ie 401 euthyroids, 127 overt and 48 subclinical hypothyroids, 205 overt and 80 compensated hyperthyroids). The TSH test proved more effective than FT4 in discriminating both overt and subclinical dysfunctions, and, in this respect, the test association was found to add a little advantage--if any. However, the extension of the concepts of diagnostic efficiency to any combination of test results- favoured by their production in a single assay--provides a basis to establish diagnostic protocols and to predict costs and benefits of medical actions. PMID- 1932174 TI - Detection of focal infection by 111In-human polyclonal IgG. AB - Eleven patients with suspected foci of inflammation and/or infection were scanned with 111In-labeled polyclonal human IgG. Seven patients were suspected of having the source of their infection in the abdomen, three in the musculoskeletal system and one in the thoracic aorta. The test was truly positive in seven patients, truly negative in three and falsely negative in one. All the true positive cases showed abnormally increased radiopharmaceutical uptake at the site of infection by six hours, suggesting the diagnosis, although the intensity of uptake increased progressively 24 hours later. There were no untoward effects noted in this series. This examination is potentially useful in the early depiction of focal sources of infection/inflammation. PMID- 1932175 TI - Radiolocalization of 99mTc-labeled fragments in a melanoma xenografted model. AB - A xenograft model of human malignant melanoma was used to compare, in terms of tumor localization, the specific antimelanoma monoclonal antibody (MoAb) 225.28S with an irrelevant antibody (4C4). Both specific and non-specific 99mTc-labeled fragments were injected in 12 nude mice bearing subcutaneous tumor. The animals were then sacrificed at 6 and 24 hours post-injection and immediately dissected. Radioactivity of the tumor and normal tissues was measured in a well scintillation counter and autoradiography of tumor, liver and kidneys was also obtained. Tumor localization of 99mTc-labeled MoAb 225.28S fragments was highly specific compared with 99mTc-labeled irrelevant antibody 4C4. With the exception of the kidneys, already at six hours there was a satisfactory tumor-to-normal tissue ratio, which improved at 24 hours. However, the percentage of injected dose per gram of tumor decreased with time, probably due to the weaker bond of radiolabeled Fab' fragments to tumor cells. These results would indicate 99mTc fragments of the antimelanoma MoAb 225.28S as a suitable radiotracer in clinical nuclear medicine. PMID- 1932176 TI - Strategies for labeling monoclonal antibodies and antibody-like molecules with technetium-99m. PMID- 1932177 TI - Acute effects of adrenaline on platelet aggregation and kinetics in vivo. AB - The platelet (Plt) contribution to cardiovascular events triggered by adrenergic stress is supported by some experimental and necropsy data, but a cause and effect link and mechanism have not yet been clearly demonstrated. Adrenergic stress was simulated by three successive adrenaline (A) injections (80 micrograms/kg) in anesthetized dogs previously infused with indium111 labelled Plt (111In-Plt) for a gamma-camera study. Adrenaline induced an acute and significant decrease in the Plt aggregation ratio (PAR) and a parallel decrease in the Plt count as well as in the circulating 111In-Plt, mirroring a significant and persistent Plt sequestration mainly in the liver and spleen. The long-lasting and significant decrease in the circulating Plt count observed 15 min after each A injection can be explained by a persistent retention of Plt. Further studies are in progress in order to disclose if this corresponds to platelet microaggregate embolization in microvessels of the organs so far analysed. If this postulate can be confirmed the hypothesis of an adrenergic stress triggering of ischemic events will be justified. PMID- 1932179 TI - Pre and postoperative assessment of regional cerebral blood flow in hydrocephalus by 99mTc-hexamethyl-propylenamine oxime SPECT. AB - Cerebrovascular changes resulting from hydrocephalus still remain to be investigated. It has been suggested that hydrocephalus distorts the large feeding arteries and that the collapse of capillaries results in decreased cerebral blood flow. This clinical study was designed to evaluate the effect of shunting on regional cerebral blood flow in patients with obstructive hydrocephalus of varying duration. Technetium-99m hexamethyl propyleamine oxime (99mTc-HMPAO) was used to measure the cerebral perfusion, semiquantitatively, since the pattern of its distribution in brain is somewhat similar to that of regional cerebral blood flow (rCBF), and the pre and postoperative semiquantitative rCBF values of each lobe were calculated. Fifteen patients (8 F, 7 M) underwent both CT and single photon emission tomography (SPECT) using 99mTc-HMPAO examination before and 1 week after shunting. Mean percentage of all lobes were calculated by subtracting the preoperative mean rCBF of all lobes from the corresponding postoperative values. The patients were classified into 3 groups according to the mean percentage of all lobes. Group A: showed a marked increase in mean cortical blood flow (+ 16.00 +/- 2.9%), group B: a moderate increase (11.27 +/- 4.8%), and in group C: there was the least improvement in mean cortical blood flow (+ 1.17 +/- 2.7%). The mean duration of hydrocephalus of group A, group B and group C was 5 +/- 0.5 weeks, 8 +/- 1 weeks and more than 12 weeks, respectively. Psychological testing and clinical observation of the daily activities of the patients postoperatively showed some correlation with increased rCBF and clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932178 TI - Capping and internalization of a monoclonal antibody-surface antigen complex: a possible mode of interaction of monoclonal antibodies and tumor cells. AB - Our results demonstrate that upon incubation of 125I-3G5 (a monoclonal IgM against a membrane ganglioside antigen on RINm5F cells) with rat insulinoma RINm5F cell monolayers at 37 degrees C, the IgM is rapidly internalized. Cell bound radioactivity, detectable within 10 to 15 minutes, reaches a peak at 4 hours. By 24 hours the intracellular radioactivity has decreased to about 37.5% of the 4-hour value, accompanied by an increase in free 125I in the incubation medium. The incubation of 125I-3G5 with RINm5F cell monolayers at 4 degrees C shows that this series of events is inhibited by low temperature. Microautoradiography confirms these events indicating the presence of radiolabeled antibody on the plasma membrane as well as distinct capping processes and diffuse radioactive deposits within the cells as early as 5 to 10 minutes after initiating incubation at 37 degrees C. Electron microscopy autoradiography provides a detailed demonstration of the capping phenomenon and of endocytic vacuoles, followed at later times by the distribution of radioactive deposits throughout the cell. This model constituted by the capping of the 125I 3G5-ganglioside complex on rat insulinoma RINm5F cells may be useful in elucidating a possible mode of interaction of monoclonal antibodies and tumor cells. PMID- 1932180 TI - Preclinical detection of metastatic melanoma. AB - We present a patient with melanoma in whom the performance of combined immunoscintigraphy and immunolymphoscintigraphy indicated the presence of metastatic disease 16 months before clinical manifestation. This approach may be useful in the early detection of metastatic disease and the patient presented is a lesson that cutaneous foci of uptake should not be dismissed as false-positive in the absence of clinical correlation. PMID- 1932181 TI - Clinical evaluation of four study protocols with 99mTc-methoxyisobutylisonitrile and SPECT for detecting diseased coronary vessels. AB - Different techniques have been suggested for coronary artery disease (CAD) detection with single-photon emission computed tomography (SPECT) and 99mTc methoxyisobutylisonitrile (99mTc-MIBI). We evaluated four protocols employing myocardial SPECT with 99mTc-MIBI in separate groups of patients. The first involved stress and rest studies performed on separate days, whereas the other three involved "same day" studies. Group 1 (n = 23) was examined in separate sessions, after ergometric exercise and at rest. Group 2 (n = 24) was first injected after dipyridamole infusion, then injected again at rest after completion of the stress study. Group 3 (n = 24) was first injected at rest and imaged one hour later. Afterwards an ergometric stress was performed, with injection at peak exercise. The inverse sequence was adopted for group 4 (n = 24). All patients underwent coronary angiography. For all groups and vessels, the sensitivity and specificity for diseased coronary artery identification were not statistically different. Studies using the new myocardial perfusion tracer 99mTc MIBI may therefore be completed on the same day or on separate days according to laboratory and patient needs. Dipyridamole iv infusion proved to be as effective as ergometric exercise for diseased coronary artery identification. PMID- 1932182 TI - The 99mTc-HMPAO leukocyte scan: an alternative to radiology and endoscopy in evaluating the extent and the activity of inflammatory bowel disease. AB - Seventy-eight patients, 47 with Crohn's disease and 31 with ulcerative colitis, were studied using 99mTc-HMPAO-labelled leukocytes, in order to assess the reliability of the scan in evaluating the location and activity of the disease. The granulocyte integrity was assessed by evaluating the lung wash-out and the early liver and spleen uptake using a 20 minute initial dynamic study. The results of the leukocyte scan revealed a high correlation with radiological and endoscopic findings in the diagnosis of the inflamed bowel segments. The disease activity correlated well with uptake in the bowel, graded from 0 to 3. The leukocyte scan exactly documented the activity in the 9 cases of Crohn's disease located in the ileum and in 5 cases in which the endoscopic exploration was hampered by scarring. Four fistulae were correctly visualized. Moreover, the change in activity after therapy in 6 patients was documented. This technique provides images of excellent quality, superior to those obtainable with indium 111. PMID- 1932183 TI - A new method for faster blood clearance in radioimmuno-guided surgery. AB - A major inconvenience of intraoperative tumor detection with radiolabeled monoclonal antibody (MoAb) by means of a probe is the long interval needed between the injection of MoAb and surgery (at least 20 days). We describe a new method which entails injection of 125I-labeled biotinylated monoclonal antibodies and cold avidin in order to obtain a rapid blood clearance of the radiotracer. The first clinical application of this protocol has been carried out in a colon cancer patient operated on six days after the administration of 125I-labeled biotinylated MoAb and cold avidin, with an optimal tumor-to-normal tissue ratio and with 90% of the circulating radioactivity cleared in two days. PMID- 1932184 TI - Evaluation of left ventricular diastolic function at rest and during exercise by gated radionuclide angiocardiography in coronary artery disease patients. AB - The peak filling rate (PFR) is an index of the diastolic function and has been proposed as an excellent parameter for the evaluation and early detection of left ventricular (LV) dysfunction. This study contributes to the assessment of LV diastolic function at rest and during submaximal exercise in 19 normal subjects and in 42 patients with coronary artery disease (CAD). The PFR was compared to the ejection fraction (EF) and the peak ejection rate (PER)--both indexes of systolic LV function--after acquiring a high-resolution time-activity curve (time/frame between 10 and 30 msec) with gated radionuclide angiocardiography. In 23 patients with normal EF at rest (greater than or equal to 50%), PFR and PER were abnormally low in 87% and 43% of the cases respectively. During submaximal exercise in 13 CAD patients, EF, PFR and PER varied very little from baseline values but were significantly reduced compared to the values of normal subjects. The PFR proved to be a very sensitive indicator of LV dysfunction in coronary patients but was not capable of discriminating between one-, two- or three-vessel disease. Our results tend to show the PFR to be a good indicator of LV dysfunction at rest and during exercise and its usefulness for the assessment of LV function is becoming more and more evident in clinical practice. PMID- 1932185 TI - AIDS--ten years on. PMID- 1932186 TI - HIV among drug injectors: the epidemic and the response. PMID- 1932188 TI - When will they ever learn? Young people, health promotion and HIV/AIDS social research. PMID- 1932187 TI - Some lessons learned about risk reduction after ten years of the HIV/AIDS epidemic. PMID- 1932189 TI - The role of non-governmental organizations in the global response to AIDS. PMID- 1932190 TI - HIV and AIDS in Haiti: recent developments. PMID- 1932191 TI - Trends in HIV/AIDS behavioural research among homosexual and bisexual men in the United States: 1981-1991. PMID- 1932192 TI - The worried well: ten years of a new face for an old problem. PMID- 1932193 TI - HIV infection and intervention: the first decade. PMID- 1932195 TI - Risk of health care professionals acquiring HIV infection in Latin America. AB - This study describes the professional risk of acquiring HIV infection while caring for AIDS patients at a teaching hospital in Brazil. Since 1985 we have tested health care professionals (HCP) for HIV-1 antibody after accidents with blood and body fluids from AIDS patients. The blood samples were tested twice using an ELISA FDA approved test and, if positive, we performed Western blot. Two hundred and forty seven health care professionals reported 338 accidents (50% were percutaneous and 22% were mucous membrane exposures to blood). A further 404 HCPs reported no occupational exposure but wanted to be tested. From 247 HCPs with at least one accident, we analyzed 115 with more than 6 months of follow up. None were HIV antibody positive. Nobody received zidovudine as a prophylaxis. Of the 404 HCPs with no accident, 6 (1.5%) were positive and had confirmed risk factors for HIV. Our results support other studies that report a low occupational risk (about 0.4%) of acquiring HIV infection. PMID- 1932194 TI - HIV infection in children. PMID- 1932196 TI - An evaluation of an education programme on HIV infection using puppetry and street theatre. AB - 'Puppets Against AIDS' is a novel educational medium being used to try to reduce the spread of HIV infection in South Africa. It involves the use of street theatre employing two-metre-high puppets who act out a story of how one person, who is infected with HIV, passes it onto a series of other people until he eventually dies. The puppet show was evaluated in two phases. The first involved a content analysis of a video recording of the show by a multidisciplinary group, according to a set of criteria for appropriate education on HIV infection. This show was found to be professional and comprehensive in terms of the educational messages provided. Some suggestions were made for improvements. The second phase was a before and after study of the impact on the audience at a series of live shows. The show made a significant contribution to knowledge and intended behaviour in the short term. Overall it was felt that the show does make a valuable contribution, but could be made more effective if incorporated into existing community-based education programmes on HIV infection. PMID- 1932197 TI - Psychosocial needs expressed by the natural caregivers of HIV infected children. AB - The presence in a family of a young child with AIDS, with the exception of a small number of transfusion-infected children, implies almost necessarily the presence of an infected adult, usually the mother. The problem in such a situation is not that of a child with a fatal illness but that of an entire family. Our study included a sample of thirty natural caregivers. These were mostly mothers but others responsible for the care of a seropositive child, such as fathers, aunts and grandmothers, were also included. The aim of the project was to describe their perceptions of their own psycho-social needs. Our results reveal that these caregivers are economically disadvantaged. They need help in coping with stress and their life situation. Their need to confide in others is frequently not met. However, the need to learn how to protect themselves and other members of the family against both HIV and other infections and to know the course and the treatments associated with this disease are seen by them, both as being very important and as being well met, particularly by the health professionals who care for them. PMID- 1932198 TI - World Health Organization Global AIDS Statistics. PMID- 1932199 TI - Identification of T. pallidum polypeptides: a comparative study between the protein profiles of in vitro cultivated and in vivo propagated Treponema pallidum subsp. pallidum by two-dimensional polyacrylamide gel electrophoresis. AB - Protein profiles of in vivo propagated and in vitro cultivated Treponema pallidum subsp. pallidum (Nichols strain) were analyzed using two-dimensional gel electrophoresis (2D-PAGE). A comparative study between the two protein profiles (as detected by silver stain, Western blotting, and autoradiography) demonstrated two in vitro synthesized polypeptides with approximate molecular masses of 29- and 35 kDa (both with pI 5.62) which were absent in the protein profile of the in vivo propagated T. pallidum. It also was demonstrated that the in vitro cultivated organisms lacked an antigenic polypeptide (as judged by Western blots) of approximate molecular weight 35 kDa (pI 5.34) which was present in the in vivo propagated organisms. To determine the cellular location of these polypeptides, the outer membrane proteins of T. pallidum was extracted with Triton X-114. The extracted proteins were subjected to phase partitioning and the 2D-PAGE protein profiles of the detergent and aqueous phases were compared. The results indicated that in vitro cultivation caused some changes in the cytoplasmic protein profiles of T. pallidum, but no changes were detected in the profiles of the membrane proteins. PMID- 1932200 TI - Mobility and electrophoretic mobility of long linear polymer molecules in gels. AB - Theoretical expressions for mobility and specific (per unit charge) electrophoretic mobility of long linear molecules in gels are derived in one dimensional approximations. The influence of the gel is described by a voluminal friction coefficient which is shown to be a reciprocal of specific hydrodynamic permeability of the gel. The nonmonotonous profile of liquid flow velocity in the vicinity of the molecular surface is obtained. Near the surface of the molecule, the liquid flows in the direction of electrophoretic movement. At a distance from the molecule, the direction of liquid flow is in the opposite direction. The distance of the point with zero velocity from the surface of the molecule decreases with increase of gel density. The specific electrophoretic mobility of a straight molecule in the gel is equal to half the harmonic average of the mobility of the molecule in the gel and the specific electrophoretic mobility of the same molecule in gel-free electrolyte solution. The theoretical expression for friction coefficient is given. The results will be used for theoretical analysis of PFGE experiments. PMID- 1932201 TI - Tension of DNA molecules and angular dependence of PFGE efficiency: a theoretical analysis. AB - The analysis of DNA separation in zone 1 of PFGE is made for both obtuse and sharp angles between pulsed fields on the basis of expression for electrophoretic velocity of the DNA molecule in the gel. Specific classes of DNA conformations are used for calculations, i.e., straight and one-angle molecules are considered. In accordance with experimental observations, higher efficiency of DNA separation for obtuse angles is shown. An algorithm of direct molecular length calculation is proposed on the basis of measured displacements of given molecular band for obtuse and corresponding sharp angles between pulsed fields. The expression for tension in the DNA molecule is given, which is important for discussion of DNA orientation and stretching and for estimation of critical fields which may cause the rupture of DNA molecules and/or gel fibers. PMID- 1932202 TI - A new device for measuring distribution of electric fields in isothermic gel electrophoresis. AB - Electrophoretic potentials inside a polyacrylamide slab gel were measured by a platinum electrode probe holder. These electrodes were inserted into the gel and the distribution in space of electric fields was explored by a multiplexing procedure. Horizontal and vertical arrays of electrodes enabled the evolution of average fields and local potential gradients to be monitored during electrophoretic migration. The results show the nonhomogeneity of mean field strength measurement along a slab gel, the dependence of the potential distribution according to the chemical composition of buffers, moving boundary detection and the resulting potential gradient variation resulting from conductance variation on either side of the boundaries. The role played by the gel and the electrode geometry in the map of potential distribution is underlined. PMID- 1932203 TI - Preparative isoelectrofocusing and high resolution 2-dimensional gel electrophoresis for concentration and purification of proteins. AB - We have analysed the potential of liquid phase isoelectrofocusing allied to high resolution 2-dimensional gel electrophoresis for concentrating and purifying in particular plasma proteins present in low concentrations. The primary fractionation step, liquid phase isoelectrofocusing, offers several advantages. Firstly, it allows protein profiles to be examined within defined pH ranges. Additionally, it confines the bulk plasma proteins to their respective pI ranges, allowing larger quantities of protein to be employed for the second fractionation phase. Concurrently, it concentrates proteins present at low concentrations, also by restricting them to their pI ranges. Yields are such that detailed characterisation studies of the proteins can be undertaken, providing the means of generating comprehensive data banks to complement plasma protein maps. The procedure should be applicable to a wide range of biological fluids and tissues. PMID- 1932204 TI - An electrophoretic method to evaluate DNA polymerase activity. AB - We have devised an easy non-radioactive assay to evaluate the activity of six different DNA polymerases: the Klenow fragment of E.coli DNA Polymerase I, Taq DNA Polymerase, Sequenase, Moloney Murine Reverse Transcriptase, T7 DNA Polymerase and E.coli DNA Polymerase I. The method is based on the differential mobility of single stranded DNA compared to that of double-stranded DNA in agarose gel electrophoresis. PMID- 1932205 TI - Characterization of Mycobacterium species by sodium dodecyl sulfate polyacrylamide gel electrophoresis. AB - A rapid method has been standardized for extraction and SDS-PAGE analyses of mycobacterial cellular protein. Complex patterns were reproducibly obtained of the 31 reference strains or clinical isolates studied, belonging to 11 species. These patterns were species specific; thus this method could be an easy tool for mycobacterial strain characterization. PMID- 1932206 TI - Synthesis and phosphorylation of nuclear matrix proteins following a toxic dose of retinoic acid in cycling and differentiating HL-60 cells. AB - Exposure of HL-60 cells to 2 microM retinoic acid, twice the dose necessary for differentiation, initiated protein synthesis within 2 h exposure in the nuclear matrix proteins and phosphorylation of a subfraction of these proteins, designated the phenol-soluble nuclear proteins. These processes were examined by fluorography of two-dimensional polyacrylamide gels. Three cell-cycle related stress proteins (22, 70c, 70x Mr x 10(-3)), were seen in the nuclear matrix fraction that were synthesized early and disappeared rapidly following dosing with retinoic acid. In control cells, protein 120 was also cell-cycle related and showed modest synthesis in nuclear matrix and strong phosphorylation in phenol soluble fraction. Within 5 h after dosing, p120 exhibited alteration in phosphorylation as evidenced by mapping of [32P]-labeled peptides. Two nuclear matrix proteins, p52 and p55, incorporated [3H] retinoic acid rapidly, were cell cycle-related, and disappeared within 12 h of dosing. Progressive increases in the labeling of the nuclear matrix and phenol-soluble nuclear proteins with increasing retinoic acid exposure was apparent in G2-phase at 96 h time-after dosing. PMID- 1932208 TI - Synthesis and biochemical characteristics of nucleoproteins following a toxic dose of retinoic acid in cycling and differentiating HL-60 cells. AB - Exposure of HL-60 cells to 2 microM retinoic acid (RA), twice the dose necessary for differentiation, initiated rapid synthesis (2 h) of the nuclear stress proteins (SPs) e.g., 90, 70c, 70x, 22 (Mr x 10(-3)) during the G0 + G1 phase of the cell cycle as observed by polyacrylamide gel electrophoresis (PAGE). Synthesis of SPs was cell cycle correlated and not dependent on time-after dosing, and all labeling disappeared from these proteins within 48 h of RA exposure. Stress proteins were not elicited with a 1 microM dose or less of retinoic acid. Non-stress nuclear proteins revealed changes in synthesis levels (e.g., actin, lamins, tubulins) which were cell cycle related and temporally associated with dosing. A major non-stress nuclear protein (Mr 120,000) which possessed an affinity for actin in binding assays, was cell cycle related in control cells, and was suppressed in synthesis in cells exposed to 2 microM retinoic acid. Two additional nuclear non-SPs 51 and 55 (Mr x 10(-3)) covalently bound the isotope [3H]retinoic acid, and their incorporation was cell cycle correlated during early periods of RA exposure. Except for the induction of SPs, the autoradiographs of nuclear proteins of RA dosed HL-60 cells, showed more quantitative than qualitative changes. PMID- 1932207 TI - Abnormal protein in the cerebrospinal fluid of patients with a submicroscopic X chromosomal deletion associated with Norrie disease: preliminary report. AB - Norrie disease is an X-linked recessive disorder characterized by congenital blindness and, in many cases, mental retardation. Some Norrie disease cases have been shown to be associated with a submicroscopic deletion in chromosomal region Xp11.3. Cerebrospinal fluid (CSF) was collected from four male patients with an X chromosomal deletion associated with Norrie disease. CSF proteins were resolved using two-dimensional gel electrophoresis and then analyzed by computer using the Elsie V program. Our analysis revealed a protein that appears to be altered in patients with Norrie disease deletion. PMID- 1932209 TI - Two-dimensional gel electrophoretic comparison of cytoplasmic proteins in C3H10T1/2 cells, a chemically transformed 10T1/2 line, and a transformation resistant C3H mouse ventral prostate cell line. AB - The cytoplasmic proteins from three cell lines derived from the C3H mouse were compared after treatment with benzo(a)pyrene by two-dimensional gel electrophoresis and computerized image analysis. The three C3H lines were the transformable 10T1/2, the transformation resistant CVP and the methylcholanthrene transformed 10T1/2Cl line. Specialized algorithms were used to analyze gel images to record and compare individual proteins in the three cytoplasmic preparations. Multiple replicate gels were used to construct a master image to insure all the proteins were represented in the analytical system. In studies designed to examine the efficacy of utilizing image analysis, benzo(a)pyrene treatment caused significant alteration in the expression of numerous proteins in all three cell lines. Comparative analysis between cell types also showed most of the induced and repressed proteins were unique to a given cell line and did not match the induced or repressed proteins in either of the other cell lines. These results suggest that the response to chemical carcinogen treatment may be somewhat cell specific and result in a variable response to the cells ability to respond to the chemical insult. PMID- 1932210 TI - Genetic studies of human apolipoproteins. XIX. Apolipoproteins E and A-IV phenotyping from whole blood and blood stains. AB - Apolipoproteins E and A-IV reveal common, genetically determined, structural polymorphisms, which can be detected in serum or plasma, using isoelectric focusing and immunoblotting techniques. In the present study, we have investigated the possibility of detecting the gene products of these two polymorphic loci in whole blood and blood stains. A total of 68 plasma samples and their corresponding whole blood samples were screened. Phenotypic patterns obtained in whole blood were identical to those obtained in plasma for both the APO E and APO A-IV polymorphisms. The signal-to-noise ratio in the APO E patterns was higher in whole blood than in fresh plasma. The gene products of both the APO E and APO A-IV were found to be very stable in several months old blood stains. The detection of apolipoprotein polymorphisms in whole blood and blood stains signifies their potential applications, on a wider scale, to several areas including forensic serology, paternity testing, clinical and population genetic studies. PMID- 1932211 TI - High-resolution two-dimensional protein electrophoresis of pathological plasma/serum. AB - The potential usefulness of an optimalized high-resolution two-dimensional gel electrophoresis (2-DGE) protocol was studied by comparative analysis of plasma/serum obtained from apparently healthy individuals and from patients with a few selected known diseases. Despite their apparent complexity, patient electrophoretograms revealed readily detectable modifications of the 'reference' protein profile for those selected diseases (listed below). Abnormal profiles were characterized by presence or absence of particular spots, by reduction or enlargement of spot size, or by alterations of spot microheterogeneity. Combinations of several modifications enabled different 'disease-associated spot pattern' to be distinguished on the protein maps of patients with: monoclonal gammopathies, hypogammaglobulinemia, hepatic failure, chronic renal failure and hemolytic anemia. This study demonstrates that identification of plasma/serum protein alterations by 2-DGE allows a few selected diseases to be diagnosed solely on the basis of protein map modifications. PMID- 1932212 TI - New hydrazone derivatives of adriamycin and their immunoconjugates--a correlation between acid stability and cytotoxicity. AB - New N-substituted hydrazine linkers were synthesized and their hydrazone derivatives of adriamycin were prepared. These functionalized adriamycin derivatives were conjugated with a monoclonal antibody, 5E9. The release rate of adriamycin from the hydrazones and from some of the conjugates was studied, and their relationship to the IC50's of the conjugate against 5E9-positive Daudi cells was investigated. PMID- 1932213 TI - Conjugation of p-aminophenyl glycosides with squaric acid diester to a carrier protein and the use of neoglycoprotein in the histochemical detection of lectins. AB - The coupling of p-aminophenyl 2-acetamido-2-deoxy-3-O-beta-D- galactopyranosyl beta-D-galactopyranoside (gal-beta 1,3-galNAc) to bovine serum albumin (BSA) was achieved by using 1,2-diethoxycyclobutene-3,4-dione (squaric acid diester) as a new coupling reagent. Two selective consequential steps afforded the desired neoglycoprotein: reaction of the p-aminophenyl group of gal-beta 1,3-galNAc with squaric acid diester gave the corresponding squaric acid amide ester, which was transformed into the BSA conjugate by coupling with the lysyl epsilon-amino group of BSA through formation of a squaric acid 1,2-bisamide. The experimental conditions for the reactions and the optimization of average were performed by using p-anisidine as model substance, the methyl group substituting for the carbohydrate part of a p-aminophenylglycoside. Neoglycoproteins have proven to be valuable tools for lectin detection. To evaluate the properties of this type of probe, the obtained neoglycoprotein with the histochemically crucial T-antigen structure was used for glycocytological and glycohistochemical studies. Three cultured human tumor cell lines and tissue sections from human breast carcinomas were chosen. Its efficiency was similar in comparison to measurements with a probe, derived by diazotization with the p-aminophenyl glycosides of gal-beta 1,3 galNAc and already shown to be a reliable marker for lectin localization in tissue sections and cultured cells. PMID- 1932214 TI - Preparation of well-defined protein conjugates using enzyme-assisted reverse proteolysis. AB - A two-step approach to the production of well-defined protein conjugates is described. In the first step, a linker group, carbohydrazide, having unique reactivity (a hydrazide group) is attached specifically to the carboxyl terminus by using enzyme-catalyzed reverse proteolysis. Since the hydrazide group exists nowhere else on the protein, specificity is assured in a subsequent chemical reaction (formation of a hydrazone bond) of the modified protein with a molecule (chelator, drug, or polypeptide) carrying an aldehyde or keto group. The product is sufficiently stable at neutral pH, no reduction of the hydrazone bond being necessary for the hydrazones described. Protein modification is thus restricted to the carboxyl terminus and a homogeneous product results. With insulin as a model, conditions are described for producing such well-defined conjugates in good yields. The use of other linker groups besides carbohydrazide, and applications of these techniques to antibody fragments, are discussed. PMID- 1932215 TI - Technetium labeling of monoclonal antibodies with functionalized BATOs. 1. TcCl(DMG)3PITC. AB - BATO (boronic acid adduct of technetium dioximes) complexes, TcCl(dioxime)3BR, were prepared in which the boron substituent (R) was the protein-reactive m phenyl isothiocyanate (PITC). The 99TcCl(dioxime)3PITC complexes [dioxime = dimethylglyoxime (DMG) or cyclohexanedione dioxime (CDO)] were prepared from 99Tc(dioxime)3(mu-OH)SnCl3 and characterized. The X-ray crystal structure of 99TcCl(DMG)3PITC was determined. The 99mTc complexes were prepared from 99mTcO4- in a process using a freeze-dried kit, either in a one-step procedure or via 99mTcCl(dioxime)3. Initial labeling studies with 99mTcCl(dioxime)3PITC were performed on glycine and polylysine and, subsequently, on mouse IgG and the B72.3 monoclonal antibody. Covalent attachment of 99mTcCl(DMG)3PITC to B72.3 was demonstrated by SDS-PAGE electrophoresis. B72.3 labeled with 99mTcCl(DMG)3PITC displayed high binding to a TAG 72 affinity column and had a distribution in normal mice similar to that reported for iodine-labeled B72.3. PMID- 1932216 TI - Astatine-211 labeling of an antimelanoma antibody and its Fab fragment using N succinimidyl p-astatobenzoate: comparisons in vivo with the p-[125I]iodobenzoyl conjugate. AB - Astatine-211 labeling of an antimelanoma antibody, NR-ML-05, and its Fab fragment with N-succinimidyl p-[211At]astatobenzoate (2a) has been described. Preparation of the astatinated intermediate 2a was accomplished by distilling astatine-211 from an irradiated bismuth target directly into a reaction mixture containing an organometallic compound, N-succinimidyl p-(tri-n-butylstannyl)benzoate (1), and an oxidant, N-chlorosuccinimide, in 5% HOAc/MeOH. Trapping of distilled astatine as 2a was found to be efficient, resulting in 70-90% yields based on the amount of astatine-211 in the reaction mixture. The dry distillation technique employed gave recoveries of astatine-211 which ranged from 20% to 75%. Conjugation of 2a to NR-ML-05 and its Fab fragment was accomplished in 40-60% yields. The [211At]astatobenzoyl-conjugated antibodies were found to be stable in vitro when challenged by strong denaturants and nucleophilic reagents. Coinjected dual labeled studies of the 2a astatinated antibodies and the same antibodies labeled with N-succinimidyl p-[125I]iodobenzoate (2b) in athymic mice bearing the human tumor xenograft A375 Met/Mix demonstrated that both radiolabeled antibodies had equivalent tumor localization. Data from the dual-labeled biodistribution of the intact antibody suggests that the astatine is stably attached. Data from the dual labeled Fab fragment suggests that a portion of the astatine label is released as astatide, either from the astatinated Fab or from a catabolite. PMID- 1932217 TI - A convenient synthesis of bifunctional chelating agents based on diethylenetriaminepentaacetic acid and their coordination chemistry with yttrium(III). AB - The bifunctional chelating agents N,N,N',N'',N''-pentakis(carboxymethyl)-1- [(4 aminophenyl)methyl]-diethylenetriamine and N,N,N',N'',N''-pentakis(carboxymethyl) 1-[(4-aminophenyl)methyl]-4- methyldiethylenetriamine were prepared in six-step syntheses in overall yields of 38% and 31%, respectively. The use of bromoacetate esters in the synthesis allowed large-scale flash chromatographic purification of reaction products. The synthesis of N,N,N',N'',N''-pentakis(carboxymethyl)-1- [(4 aminophenyl)-methyl]-4-methyldiethylenetriamine resulted in a mixture of two diastereomers. Chelation of yttrium-(III) with these bifunctional chelating agents resulted in 1:1 chelates. In the case of N,N,N',N'',N'' pentakis(carboxymethyl)-1-[4- aminophenyl)methyl]diethylenetriamine, two diastereomers were observed upon chelation, as expected. In the case of N,N,N',N'',N''- pentakis(carboxymethyl)-1-[(4-aminophenyl)-methyl]-4- methyldiethylenetriamine, only three of the four anticipated diastereomers were observed. PMID- 1932218 TI - Backbone-substituted DTPA ligands for 90Y radioimmunotherapy. AB - Four new bifunctional diethylenetriaminepentaacetic acid (DTPA) ligands were synthesized to provide an improved chelating agent for radioimmunotherapy with 90Y. The new DTPA ligands contained a 4-isothiocyanatobenzyl group (pSCNBz) substituted onto the carbon backbone of DTPA for use in linkage to immunoprotein. Methyl groups were strategically incorporated onto the backbone of the ligands via a peptide route to provide 2-pSCNBz-5-Me-DTPA (2) and 3-Me-6-pSCNBz-DTPA (3). Addition of these functionalities was expected to sterically hinder the release of radiometal from the chelate. A new monosubstituted ligand, 3-pSCNBz-DTPA (4), was also prepared in order to determine whether a shift in position of the linking group had an effect on the in vivo stability of the yttrium complex. Additionally, by modification of known methods, a disubstituted DTPA ligand, 2 pSCNBz-6-Me-DTPA (1), was prepared. PMID- 1932219 TI - Nutritional support in cancer treatment. AB - The role of artificial nutritional support, ie, both intravenous and enteral nutrition by infusion of chemically defined nutrients, is considered adjunct to cancer treatment. Despite a vast body of literature reflecting numerous attempts to demonstrate a supportive role for nutrition, little benefit has actually been confirmed in controlled investigations regarding outcome and objective remission in progressive cachexia. However, the impact of nutritional support on quality of life has only been considered in a few preliminary attempts in cancer patients. We suggest that the lack of evidence in cancer treatment for a significant role of nutritional support in a general sense is probably explained both by inappropriately designed investigations and by the unrecognized fact that standard clinical nutrition is hampered by nutrition-related inefficiencies that have not been well described before. Improved understanding of such deficiencies and the development of more sophisticated regimens in line with "nutrition pharmacology" instead of plain feeding with calories and protein may change this fallacy in the near future. PMID- 1932221 TI - Intravenous access devices for supportive care of patients with cancer. AB - Reliable long-term venous access is crucial as a pathway for the delivery of many current chemotherapeutic agents, as well as for the supportive measures needed to sustain patients during their recovery from the toxic effects of these drugs. Many access devices are now available, but all carry the risk of infection, thrombosis, and complications related to their insertion. Recent advances in technology and the use of antibiotics and anticoagulants offer the opportunity to reduce the rate of many of these complications. PMID- 1932220 TI - Use of blood and blood products for supportive care in cancer treatment. AB - Prophylactic platelet transfusion can prevent spontaneous hemorrhage in thrombocytopenic cancer patients undergoing intensive treatment, but it is limited by the development of platelet alloimmunization. Exclusive use of leukocyte-depleted blood products delays or prevents the development of platelet alloimmunization and also decreases the frequency of chill and fever reactions and reduces the transmission of cytomegalovirus and possibly other viral infections. Management of disease refractory to platelet transfusion remains a difficult problem. Intravenous immune globulin reduces the incidence of infection and may modify the severity of gram-negative sepsis, decreases the incidence of acute graft-versus-host disease, and may benefit some patients with platelet refractoriness. All blood products given to severely immunocompromised patients, including those undergoing chemoradiotherapy and high-dose therapies, should be irradiated. In addition, designated donor transfusions from first-degree relatives (even when given to immunocompetent patients) should be irradiated. PMID- 1932222 TI - Supportive care for viral infections in cancer patients. AB - Viral infections are more frequent and more severe in patients with cancer. As treatments for malignancy become ever more aggressive, the supportive care must also advance or the gains from innovative antineoplastic treatments will be lost to morbidity and mortality from secondary immune suppression and opportunistic infections. While empiric antibacterial and antifungal therapies for neutropenic leukemia patients were improving patients' survival, viral infections in cancer patients were often relegated to a clinical footnote in review articles since little could be done about them. Recently, however, acyclovir, ganciclovir, immunoglobulins, and ribavirin have given new opportunities for successful management of severe viral opportunistic infections in patients with leukemia and in bone marrow and other transplant patients. PMID- 1932223 TI - Hematopoietic growth factors as supportive therapy for cancer- and chemotherapy induced conditions. AB - A number of human hematopoietic growth factors have been genetically cloned and recombinant proteins produced. Several phase I and II clinical trials have already been published and results from phase III studies are becoming available. The use of erythropoietin to alleviate chemotherapy-induced myelosuppression is being tested. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor have been extensively studied in patients receiving chemotherapy at standard or escalated doses and after bone marrow transplantation and appear to ameliorate chemotherapy-induced neutropenia and to speed bone marrow engraftment after high-dose cancer therapy. Interleukin-3 and interleukin 6 are quite early in their clinical development, but appear able to alleviate post-chemotherapy thrombocytopenia. PMID- 1932224 TI - Intensive care in the treatment of cancer patients. AB - Intensive care has been important in the treatment of cancer patients during the last decade. The main indications for admission to the intensive care unit are postoperative recovery, critical complications of cancer and its treatment, intensive anticancer treatment administration monitoring, and acute disease unrelated to the neoplastic disease or its treatment. Management of such cases must take into account the patient's fragility resulting from the presence of a severe chronic underlying disease with systemic effects. In the future, intensive care may play an important role in the development of oncology not only as supportive care for patients but also in the active development of new anticancer therapies. PMID- 1932225 TI - Laboratory investigation, genetics, and experimental models in sarcomas. AB - The sarcomas, particularly those of soft-tissue origin, pose substantial diagnostic challenges for the clinician and pathologist. Several small round cell sarcomas, including Ewing's sarcoma, peripheral primitive neuroectodermal tumor, and alveolar rhabdomyosarcoma, can be difficult to distinguish from one another. These same sarcomas can be difficult to distinguish from other small round cell tumors, including non-Hodgkin's lymphoma and neuroblastoma. Spindle cell sarcomas, including malignant peripheral nerve sheath tumor, synovial sarcoma, and leiomyosarcoma, present similar diagnostic challenges. This review discusses 1) recent advances in immunohistochemistry, electron microscopy, and cytogenetics that enable a specific diagnosis in virtually all sarcoma cases; 2) cell biology and oncogenetic implications of novel morphologic and genetic findings in sarcomas; and 3) clinical implications of the recent characterization of several family cancer syndrome genes. PMID- 1932226 TI - Advances in the diagnosis and management of sarcomas. AB - Advances in the molecular biology and importance of tumor suppressor genes in the development and tumor progression of sarcomas are reflected in the literature of 1990. In particular, the discovery of tumor suppressor gene syndromes, such as Rb1 gene and p53 gene defects manifested in "cancer families," were made possible by their association with sarcomas, otherwise rare tumors. It is growing clear that these genes are involved in some way in sporadic cases as well. Treatment for soft tissue sarcomas has not progressed as well. While function-preserving surgery with radiotherapy has been established, the utility of chemotherapy has been limited by the lack of active drugs. Greater efforts are needed in the clinic-laboratory interface to determine the mechanisms of this resistance and ways to circumvent them. PMID- 1932227 TI - Rhabdomyosarcoma and other soft tissue sarcomas of childhood. AB - Often treated as a single clinical entity, the pediatric soft tissue sarcomas include neoplasms of diverse histology that can originate from any anatomic site and exhibit varied patterns of local spread and metastasis. Recent developments with potential clinical impact include new diagnostic and prognostic markers stemming from advances in molecular biology, and increasing concern for the late effects of therapy in a growing population of long-term survivors. Initial clinical data indicate the value of MyoD1 protein expression in classifying previously indeterminate primitive undifferentiated tumors. The reported sensitivity and specificity of P-glycoprotein expression for the identification of chemoresistant disease in pediatric sarcomas should spawn studies to clarify its prognostic value and potential therapeutic strategies to circumvent the multidrug-resistance phenotype. Tumor cell DNA ploidy may also have prognostic and diagnostic value. An abundant interest in alleviating the late effects of adjuvant therapy and surgery is reflected in many clinical reports by oncologists, surgeons, radiotherapists, ophthalmologists, and other specialists. PMID- 1932228 TI - Ewing's sarcoma. AB - Ewing's sarcoma and primitive neuroectodermal tumor are rare tumors of childhood, both considered to be small round blue cell tumors of childhood. Recent advances have been made regarding the histogenesis and biology of these tumors. Current thinking links Ewing's sarcoma and primitive neuroectodermal tumor by a shared chromosomal translocation and by evidence of neuroectodermal origin. Advances in chemotherapy have resulted in the cure of most patients presenting with Ewing's sarcoma. This review briefly outlines the year's literature on the histogenesis, biology, and treatment of this tumor. PMID- 1932229 TI - Recent developments in genetic mechanisms, assessment, and treatment of osteosarcomas. AB - Osteosarcoma is the most common malignant bone tumor in children and adolescents. The tumor, which is composed of malignant spindle cells that produce osteoid, typically occurs in the diaphyseal region of long bones; about half of all osteosarcomas arise in the distal femur or proximal tibia. Clinically detectable metastases are present in about 20% of patients at diagnosis, and most patients have subclinical metastases. Effective therapy with complete surgical resection of tumor and intensive multiagent chemotherapy results in the cure of over 50% of patients with osteosarcoma. Recent developments of importance include an improved understanding of the importance of the p53 gene in the pathogenesis of osteosarcoma, the description of preclinical models, the development of improved imaging techniques for determining tumor extent and responsiveness to chemotherapy, and refinements in therapy. PMID- 1932230 TI - Chondrosarcoma and other rare bone sarcomas. AB - The clinical staging of bone tumors, even rare ones, has been much improved with the availability of better imaging techniques. Once diagnosis of a rare bone tumor has been made, close consultation between clinician, radiologist, and pathologist is essential for optimal treatment. Recent advances in the staging procedures and better assessment of prognostic factors should allow for a more optimal individualized treatment plan. PMID- 1932231 TI - Epidemiology and early detection of colorectal cancer. AB - Further information consolidating the roles of dietary fat and fiber and physical inactivity in colorectal carcinogenesis has been published in the year under review. A large cohort study identified animal fat as the most important dietary risk factor, and a meta-analysis of fiber supported the role particularly of vegetable fiber in protection. An important population-based study in Scandinavia identified age at onset of ulcerative colitis as a factor independent of length of follow-up; risk at 35 years after onset was 40% for those with early-stage onset. An update at the St. Mark's Hospital, London, surveillance experience offers measured support for endoscopic screening for dysplasia and curable cancer. A unique paper from Japan defines a relative risk of cancer after polypectomy of 2.3. A case-control study of occult blood screening showed that the sensitivity of guaiac testing for fecal occult blood (Hemoccult, Smith Kline Diagnostics, CA) for asymptomatic colorectal cancer is just under 50%. Cost benefit modeling suggests that annual occult blood testing and 3- to 5-yearly flexible sigmoidoscopy are optimal. PMID- 1932232 TI - Diagnosis and imaging of gastrointestinal tract cancers. AB - Recent trends in the diagnosis and imaging of cancers of the gastrointestinal tract include developments in screening for colorectal cancer and innovations in ultrasonography and magnetic resonance imaging of primary and metastatic hepatic tumors. Mathematical models suggest that screening for colorectal cancer will be as cost-effective as several other widely accepted screening programs, including the Papanicolaou smear for cervical cancer and screening mammography. There is considerable discussion regarding the relative roles of procedures such as fecal occult blood testing, sigmoidoscopy, colonoscopy, and radiology in screening strategies. The issue remains unsettled. In ultrasonography, the use of intraoperative ultrasound allows for the detection of more metastatic lesions in the liver than do preoperative computed tomography and ultrasound. Esophageal endoscopic ultrasonography has been used for the preoperative assessment of depth of invasion by esophageal cancer. The technique is limited in cases of stenotic cancer in which the endoscope cannot be passed through the lesion. Similarly, endorectal ultrasound can be used for staging of rectal cancer. Color Doppler ultrasound has been used for the evaluation of blood flow in relationship to hepatic neoplasms. Magnetic resonance imaging has been used not only for detecting liver tumors but also for differentiating between neoplasm and hemangioma. PMID- 1932233 TI - Therapy for colorectal cancer. AB - Recent advances in systemic therapy involve the biochemical modulation of fluorouracil. New trials combining either leucovorin or N-(phosphonoacetyl)-L aspartate (PALA) with fluorouracil have demonstrated increased response rates. Recent trials of interferon-alpha with fluorouracil have not confirmed the high response rates reported in previous trials. Advances in regional therapy include the addition of either leucovorin or systemic therapy to fluorodeoxyuridine. Some adjuvant trials of portal vein infusion have shown increased survival, though the incidence of liver metastases was not decreased. A large adjuvant trial in rectal cancer demonstrated improved survival and decreased local recurrences when fluorouracil and methyl-CCNU were added to radiation therapy. PMID- 1932234 TI - Supportive care. PMID- 1932235 TI - Sarcomas. PMID- 1932236 TI - Gastrointestinal tract. PMID- 1932237 TI - [Fungal infections in liver transplantation]. PMID- 1932239 TI - [Aeromonas spp. isolated from human feces. Species and pathogenicity factors]. AB - The role of Aeromonas genus as a primary intestinal pathogen is still a matter of controversy. We have studied the isolation of Aeromonas spp. from human stools samples, looking for the production of pathogenic factors and its relationship with different species. From a total of 471 strains isolated, 241 were A. caviae, 127 A. sobria, 89 A. hydrophila and 14 non-typable strains. The pathogenic factors production was studied in a bacteria-free filtrate from a 18 hours trypticase-soy broth culture. Enterotoxin production was assessed by suckling mice test, cytotoxin production by using Hela cells monolayer and hemolysin production by double dilution from the filtrate, plated in microdilution plates, against rabbit red-blood cells. Enterotoxin production test was positive for A. sobria, A. hydrophila and A. caviae in 81.1%, 62.9% and 7.0% of strains respectively. Cytotoxin production was also positive for these species in 96.6%, 76.4% and 4.1%, and hemolysin production was positive in 95.3%, 70.7% and 2.4% of the strains respectively. PMID- 1932238 TI - [Invasive mycoses in liver transplantation]. AB - Seventy three adults underwent orthotopic liver transplantations between February 1987 and November 1989 and were followed (54 retrospectively and 19 in a prospective study) with the aim of establishing the incidence of deep mycoses (3 disseminated candidiasis due to C. albicans, 1 invasive aspergillosis due to A. fumigatus and 1 invasive pulmonary aspergillosis due to A. niger and A. fumigatus). 4/5 of these infections occurred in the first month after transplantation. All the patients were associated with the following clinical risk factors: previous use of wide spectrum antibiotics (5/5); more than 1 abdominal laparotomy (4/5), due to primary failure of the graft (3/4) and thrombosis of the hepatic artery (1/4). Two of the three patients [corrected] with invasive candidiasis had previous episodes of documented fungemia. 24 patients of the group who didn't show MIP had some risk factor which in all of them was the previous use of high dose steroids and/or of wide spectrum antibiotics, in addition to the used in surgical prophylaxis. In our series, the one risk factor associated with MIP was more than one previous laparotomy (p less than 0.001). Other significant associated infections were 3 bacterial sepsis (2 due to Enterococcus faecalis and 1 due to Staphylococcus epidermidis) and one viral (Cytomegalovirus viremia). The mortality rate was 100%, however the cause of death was multifactorial. PMID- 1932240 TI - [Serologic diagnosis of Lyme disease. A pending problem]. AB - We analyze the experience in serologic diagnosis of Lyme's borreliosis. From a total of 551 patients studied from 1987 to 1989, we further evaluate 80 cases with erythema chronicum migrans or a clinical diagnosis of Lyme's disease and positive serological tests. The techniques used were IFI, ELISA1 (Whittaker Bioproducts) and ELISA2 (MarDx Diagnostics). Serological tests results were evaluated in relation to clinical data. Five cases were excluded because of no specific symptoms. There were 20 false-positive results, mainly due to other infections (HIV infection, tuberculosis, Mediterranean spotted fever and syphilis). Fifty-five patients were considered clinically of having Lyme's disease. IFI test was positive in 81.8% of all the 55 cases, ELISA2 in 58.4% of 53 cases tested and ELISA1 in 23% of 43 cases tested. Correlation between IFI and ELISA2 positive test was seen in 45% of cases. Specificity of all tests was higher than 97%. The study shows that sensitivity for all three techniques used was not optimal, and also there are some differences in their results. However, specificity was adequate. PMID- 1932241 TI - [Bacteremia in a community hospital. Review of 78 cases]. AB - We analyze retrospectively all bacteremic episodes seen between January and December, 1987 in our institution. From a total number of blood cultures performed of 897, 145 were positive (16%), and 67 of them considered as contamination (7.5%). There were 78 episodes of bacteremia in 74 patients, 38 males and 36 females. Forty-eight episodes were community-acquired and 30 were nosocomial bacteremia episodes. Aerobic bacteria were isolated in 64 cases, anaerobic bacteria in 9 cases and polymicrobial bacteremia in 5 cases. The most commonly isolated microorganism was S. epidermidis in nosocomial cases and E. coli in community-acquired cases. Predisposing conditions registered were diabetes mellitus in 16 cases (20%), cirrhosis of the liver in 3 (4%), corticosteroid therapy in 7 (9%) and surgical procedures in 19 (24%). Shock was seen in 16 cases (20%), DIC in 8 cases (10%) and ARDS in 5 (6.5%). Appropriate antibiotic treatment was used in 60 episodes (77%). Seventeen patients (22%) died. Prognostic factors identified were: nosocomial bacteremia (p less than 0.05), corticosteroid prior therapy (p less than 0.05), underlying disease UF or RF (p less than 0.0001) and the presence of shock (p less than 0.0001). Mean hospital stay was 20.1 days in bacteremic patients vs. 7.6 days in non bacteremic patients (p less than 0.00001). PMID- 1932242 TI - [Hepatitis C virus infection in different risk groups and among blood donors]. AB - We have studied serological markers of viral hepatitis type A, B, delta and C in 7,713 blood-donors, 265 patients with a clinical diagnosis of hepatitis, 41 inmates of a mental and physical retardation institution and 41 health care workers at the same institution and 35 chronic hemodialysis patients. The results showed a 0.8% anti-HCV prevalence in blood-donors, but a higher percentage (47.5%) among HBV positive patients and in two different groups of the inmates at the mental institution (12.5% and 36%). We can not establish a relationship with the presence of anti-HCV and serological markers for HBV or H-delta V, neither with any serological markers pattern of B hepatitis nor with the anti-HCV levels and pathological findings in the biopsy of the cases in which this procedure was performed. The detection of anti-HCV has two direct applications: to exclude positive blood-donors in order to reduce the risk of post-transfusion hepatitis and to better establish a precise diagnosis in patients otherwise classified of having nonA-nonB hepatitis. PMID- 1932243 TI - [Nasal carriage of Staphylococcus aureus among personnel working in a teaching hospital]. AB - We have studied prospectively the nasal carriage status of Staphylococcus aureus among all health-care workers in the Valdivia Hospital Base. A total of 522 nasal samples were evaluated. Nasal carriage rate was 34.9% for all personnel. Higher rates were seen in Pediatric wards and Central Kitchen Service. Isolated strains were resistant to penicillin (98.3%). However, sensitivity to other antimicrobial agents was high. According to the antimicrobial susceptibility pattern, we identified 12 different groups of strains or antibiotypes. Three of the multiple resistant antibiotypes (resistant to 4 or 5 antimicrobial agents) were isolated from pediatric wards. PMID- 1932244 TI - [Bacteremia caused by Streptococcus agalactiae in adults. Presentation of 6 cases]. AB - The incidence of Streptococcus agalactiae (SA) bacteremia in adults has increased in recent years, particularly in patients with severe underlying diseases. However SA is still an unusual pathogen in adults. We report 6 cases of SA bacteremia in adults, seen during 18 months. The microorganism was only isolated from the blood in 3 cases, and from blood and other locations in the remaining three cases. The age of the patients ranged from 35 to 70 years. Both sex were affected in the same proportion. In all cases except in one there was a previous underlying disease. PMID- 1932245 TI - [Validity of preclinical research in the development of new antibiotics. Pharmacokinetic aspects]. PMID- 1932246 TI - [Subacute meningitis with a facial cutaneous lesion in a patient seropositive for HIV-1]. PMID- 1932247 TI - [Disseminated hemorrhagic vesicular exanthema and pneumonia in a patient with HIV infection]. PMID- 1932248 TI - [Endocarditis caused by Corynebacterium jeikeium]. PMID- 1932249 TI - [Dermal vasculitis as the only manifestation of Q fever]. PMID- 1932250 TI - [Evaluation of a recombinant latex agglutination test for HIV-1]. PMID- 1932251 TI - [Outbreak of dermatophytosis caused by Microsporum canis in a closed community in the province of Soria]. PMID- 1932252 TI - [Perianal streptococcal disease]. PMID- 1932253 TI - [Sepsis caused by Staphylococcus epidermidis with meningeal, articular and skin involvement in a female patient addicted to parenteral drugs]. PMID- 1932254 TI - [Diaphragmatic paralysis in cervical herpes zoster]. PMID- 1932255 TI - [Pneumonitis associated with primary infection by HIV]. PMID- 1932256 TI - [Meningitis caused by Listeria monocytogenes in a patient infected by human immunodeficiency virus]. PMID- 1932257 TI - [Purulent meningitis caused by Streptococcus intermedius (S. milleri) related to an otogenic focus]. PMID- 1932258 TI - [Bacteremia of biliary origin caused by Aeromonas caviae in a healthy patient]. PMID- 1932259 TI - Discourse on the development of EEG diagnostics and biofeedback for attention deficit/hyperactivity disorders. AB - This article presents a review of work that my colleagues and I have been doing during the past 15 years developing a rationale for the diagnosis of attention deficit/hyperactivity disorder (ADHD) and treatment of ADHD employing EEG biofeedback techniques. The article first briefly reviews the history of research and theory for understanding ADHD and then deals with the development of EEG and event-related potential (ERP) assessment paradigms and treatment protocols for this disorder, including our work and that of others who have replicated our results. Illustrative material from our current research and child case studies is included. Suggestions for future experimental and clinical work in this area are presented and theoretical issues involving the understanding of the neurophysiological and neurological basis of ADHD are discussed. PMID- 1932260 TI - EMG scanning norms: caveat emptor. AB - Questions are raised as to the appropriateness of applying static normative data to EMG muscle scanning and whether currently available normative data meet standards prescribed by the principles of measurement. Potential sources of systematic measurement error emanating from hardware differences, the practitioner, and the standardization sample are also discussed. An alternative to the fixed normative approach is presented. Specifically it is suggested that raw EMG data values be scaled using a nonlinear data transformation which would result in a derived standard scan score scale. This would also allow for intermuscular and interindividual comparisons, which are not appropriate with the currently used fixed normative approach. Further, the alternative approach adheres to the principle that EMG data must be interpreted relatively and not absolutely. It is argued that this alternative would eliminate systematic error problems with regard to hardware differentials and preclude the necessity of, and the problems endemic to, norms development. Finally there is an explanation on how one could develop a muscle scanning profile similar to that in current use by many personality inventories. The profiles could then be used as normative. PMID- 1932261 TI - Conditioning of skin conductance levels through a combined instrumental-classical conditioning procedure. AB - A paucity of studies and inconsistent results characterize attempts to instrumentally condition tonic electrodermal activity. The present study was conducted to further explore the classical and instrumental conditioning of skin conductance levels (SCLs) through auditory analogue feedback. Fifty undergraduates were randomly assigned to one of five groups of equal size: instrumental conditioning alone, classical conditioning alone, instrumental and classical conditioning combined, and two control groups. The combined training group achieved significantly higher SCLs relative to the group receiving instrumental conditioning alone. PMID- 1932262 TI - Scientific and clinical biofeedback in the USSR. AB - This paper describes the history of biofeedback research and application in the USSR. The approach of USSR scientists to the study of basic mechanisms of biofeedback and the status of clinical applications of biofeedback in the Soviet Union are described. Trends in the publication of biofeedback-related papers in Russian are presented, and the present "state of the art" described. Promising prospects for biofeedback research and application are discussed. PMID- 1932263 TI - The effect of clothing on inhalation volume. AB - Diaphragmatic breathing is included as an important component of relaxation training protocols. In the present study, we report on the effectiveness of a simple behavioral technique to illustrate that choices of tight, restraining clothing significantly affect the inhalation volume of the breathing pattern. This study investigates the use of the incentive inspirometer to observe the effects of tight versus loose clothing on inhalation volume with 17 volunteer subjects. All had been trained in the use of the incentive inspirometer and slow diaphragmatic breathing (SDB) techniques. Inhalation volumes in the studies were measured with a 4000-ml incentive inspirometer and were recorded for one or two sequential breaths using SDB before and after loosening restrictive clothing. Loosening the subjects' clothing significantly increased inhalation volume. The results indicate that tight clothing significantly interferes with diaphragmatic breathing. We suggest that the demonstration of the effect of tight versus loose clothing can increase the clinician's awareness of the effects of clothing on breathing patterns. The technique also facilitates the acquisition of diaphragmatic breathing skills, and may raise the client's awareness that choices such as clothing can directly affect physiology. PMID- 1932264 TI - The role of absorption capacity in thermal biofeedback treatment of vascular headache. AB - The clinical utility of Tellegen's Absorption Scale was examined using a sample of 32 chronic vascular headache patients drawn from a larger treatment study investigating the efficacy of thermal biofeedback with vascular headache. A regression analysis found that acquisition of the hand-warming response was directly related to increase in capacity for absorption. Conversely, a trend was found for absorption capacity to be inversely related to reductions in headache frequency and intensity. Reasons for these differences in process and outcome variables are discussed. PMID- 1932265 TI - Abstracts of papers presented at the 22nd annual meeting of the Association for Applied Psychophysiology and Biofeedback. Dallas, Texas, March 15-20, 1991. PMID- 1932266 TI - [Several results of a Toxoplasma survey]. AB - A pilot Toxoplasma survey was conduct in Ciego de Avila province during the month of September, 1985, to assess, in practice, the methodologic structure proposed for the National Toxoplasma Survey. Of the 292 listed individuals, 284 were surveyed during the field work phase (97.2%) and the remaining 2.8% of no response was due mainly to the fact that dwellers were not at home during the visit. The best day for this type of survey resulted to be Sunday, in the morning. No difficulty was noted with the used modelling, and results obtained in the application of used techniques and procedures are appropriate for use in the National Toxoplasma Survey. The prevalence rate of anti- Toxoplasma antibodies was 55.9%. There was a significant association between some risk factors such as: living with cats, ingestion of non potable water and ingestion of raw meat. PMID- 1932267 TI - Graphite furnace atomic absorption spectrometric determination of blood lead with palladium modification. AB - In this work we present a graphite furnace atomic absorption spectrometric method for blood lead using palladium as a chemical modifier. Whole blood was diluted 10 fold with a 0.1% v/v triton X-100 solution; 10 microL of this solution and 10 microL of the palladium-based modifier (2 mg Pd/L, 2% w/v citric acid and 0.01 M nitric acid) were injected onto the L'vov platform by using the alternate volume mode. The following furnace operating parameters were used: (a) drying steps, 120 degrees C for 10s and 250 degrees C for 30s; (b) pyrolysis steps, 800 degrees C for 45s (with oxygen) and 1100 degrees C for 25s; (c) atomization, 1600 degrees C for 3s; (d) clean out, 2700 degrees C for 4s. Accuracy was tested by using (i) a NIST standard (SRM-909) and the Behring Control Blood for Metal 1 (OSSD 21) with lead concentrations of 23.7 +/- 2.1 micrograms/L (found: 21.2 +/- 0.7 micrograms/L) and 413 +/- 51 micrograms/L (found: 407 +/- 6 micrograms/L), respectively; (ii) recovery studies (ca. 100 +/- 1%), and (iii) a reported method (mean relative error: 5.1%). Approximate standard deviations of 0.3 (within-run) and 0.7 (between-runs) micrograms Pb/L were found in the precision study. The detection limit (3 sigma) and the characteristic mass (for a 10- microL injection volume) were 0.1 micrograms Pb/L and 15 pg/0.0044 A.s, respectively. The proposed method was used to establish the lead levels of patients with renal insufficiency; a mean concentration (+/- SD) of 59 +/- 39 micrograms Pb/L (range: 12- 160 micrograms Pb/L) was found. The method was interference-free, reliable and reproducible. PMID- 1932268 TI - [Assessment of respiratory deterioration with spirometry]. AB - Respiratory impairment was evaluated in 342 smokers and exsmokers patients, aged 21 to 79 years; 195 were male and 147 female, The American Thoracic Society (ATS) recommendations were followed. Pulmonary function tests: VC, FEV1, FVC and FEV1/FVC% were performed, using a Spirometer Spyro Analyzer, model ST-200, Fukuda Sangyo. The actual values of these tests, were compared with predictive values of Corzo, in order to evaluate the severity of respiratory impairment. In this work, respiratory impairment was found in 104 patients (30%) of 342 studied, distributed as follows: 20 (19.2%) in 20-39 years group, 35 (33.7%) in 40-59 years group and 49 (47.1%) in 60-79 years group. In relation to degree of impairment, 55 patients (52.9%) were mildly impaired, 35 (33.7%) moderately impaired and 14 (13.4%) severely impaired. It was found that 60% (21) moderately impaired patients and 64.3% (9) severely impaired were in 60-79 years group. They also had a larger history of cigarette smoking or smoked more than 30 cigarettes daily. Also a higher frequency of obstructive ventilatory defect causing respiratory impairment was found. PMID- 1932269 TI - [Anemia in pregnancy. Review]. AB - Pregnancy anemia occurs when the concentration of hemoglobin in pregnant women is less than 11 g/dl, provided that they live at sea level. Nutritional deficiencies of iron and folic acid, combined or isolated, are the main causes of this type of anemia, due to increased demands of nutrients to satisfy the needs of the fetus and the growing tissues during pregnancy. Nutritional deficiency of vitamin B12 is infrequent during pregnancy unless there are coexistant gastrointestinal abnormalities or immunological processes. The recommended therapy for iron or folic acid deficiency is oral administration of ferrous salts or folic acid, in daily doses that should not be higher than 60 mg of elemental iron or 2.5 mg of folic acid. PMID- 1932270 TI - A comprehensive method validation strategy for bioanalytical applications in the pharmaceutical industry--1. Experimental considerations. AB - The method validation strategy described consists of four components which are the prevalidation, validation proper, study proper and statistical analyses. These components constitute the platform upon which to evaluate the reliability and reproducibility of a bioanalytical method. Consideration has been given to emulate the study proper conditions to understand the method's limitations and performance expectations. The validation strategy will be presented in two papers. This first paper will describe the overall validation strategy, and the second paper will discuss the statistical analyses and data interpretation. PMID- 1932271 TI - Chiral drugs: an industrial analytical perspective. AB - In the pharmaceutical industry, chiral drug candidates introduce a unique set of challenges to all disciplines involved in the drug development process. For the analytical chemist in particular, the generation of relevant information about a variety of stereoisomeric issues is necessary. Chiral drug candidates, whether a single isomer or a mixture of isomers, require more analytical information than achiral drug candidates. This information can be derived from enantioselective spectroscopic and chromatographic techniques. Chiral analytical methods require proper development and validation to ensure accurate results. Issues related to method development and validation for complete stereochemical characterization are discussed, with primary emphasis on the generation of analytical data required for the registration of a chiral drug candidate. The presentation of pertinent analytical data depends on an awareness of the problems encountered during the development process and the appropriate use of methodology for the determination of stereoisomeric purity. PMID- 1932273 TI - Preparation and characterization of labelled interferon-gamma and the development of radioreceptor assay for interferon-gamma. AB - A 125I-labelled recombinant interferon-gamma (IFN-gamma) was prepared by the lactoperoxidase-glucose oxidase method. The specific activity of the labelled IFN gamma was 31 Bq U-1 and its molecular weight, immunoreactivity and receptor binding ability remained the same after the labelling. Using the labelled IFN gamma and FL5(-1) cells from human amniotic membrane, a radioreceptor assay was developed. Natural IFN-gamma, recombinant IFN-gamma and the labelled IFN-gamma were observed to bind to the same binding sites on the cells with similar affinity (Kd = 1.3-2.2 x 10(-10) M). The radioreceptor assay was more specific than a bioassay because the labelled IFN-gamma did not compete with IFN-alpha or IFN-beta. It was much more sensitive (90 pM) than conventional competitive radioimmunoassay (300 pM) using the same labelled IFN-gamma, and as sensitive as immunoenzymometric assay (60 pM). The radioreceptor assay should be useful not only for research on IFN-gamma but also for the determination of biological activity in process control and/or quality control of IFN-gamma manufacturing. PMID- 1932272 TI - Polarographic determination of clavulanic acid. AB - A method is proposed for the determination of clavulanic acid by differential pulse polarography. The electroactive product was obtained by hydrolysis in sulphuric medium. It shows a reduction peak, that can be used analytically, at 0.75 V (vs SCE). The optimum conditions for the polarographic signal were determined and a study was made of the different parameters affecting the electrochemical process. A polarographic procedure is proposed for the determination of clavulanic acid in a concentration range of 8.0 X 10(-6) -1.4 X 10(-4) M. The detection limit is about 2 x 10(-6) M and the relative standard deviation is 1.1%. The method was applied to the determination of clavulanic acid in the presence of amoxicillin. PMID- 1932274 TI - New modified polymeric electrodes selective to local anaesthetic compounds. AB - New polymeric electrodes responding to the cationic forms of tetracaine (TC), lidocaine (LD), and procaine (PC) were constructed by incorporating their ion pair complexes (the salts of TC, LD and PC with phosphotungstic acid) into ethylene-vinyl acetate (E/VAC) copolymer. Other ion pairing agents investigated were silicotungstate and tetraphenylborate. The phosphotungstic acid resulted in the best linear and Nernstian response. A 1:1 (v/v) mixture of dioctyl phthalate (DOP) and nitrobenzene (NB) was used as plasticizer. The electrodes exhibited linear response over the concentration ranges 10(-2)-5.6 x 10(-6), 10(-2)-2.5 x 10(-5) and 10(-2)-1.8 x 10(-5) M of TC, LD and PC, respectively. pH did not affect the electrode performances within the ranges 2.7-6.3, 2.6-6.7 and 2.8-7.5 for the three electrodes, respectively. Interferences are negligible for many organic base and alkali metal cations. Cations of similar structure interfere with LD and PC, but not appreciably with TC. Direct potentiometry was used to determine these compounds in pharmaceutical preparations with accurate results. PMID- 1932275 TI - Analysis of flucytosine dosage forms by derivative UV spectroscopy and liquid chromatography. AB - A simple second-order derivative spectrophotometric method was developed for the selective determination of flucytosine (an antimycotic drug) in the presence of 5 fluorouracil (a cytotoxic agent), its synthetic precursor and degradation product. Traces of 5-fluorouracil in flucytosine were also determined by derivative UV spectroscopy; flucytosine was removed by a selective solid-phase extraction (SPE) procedure using a strong cation-exchange sorbent. The spectrophotometric methods were applied successfully to the quality control of commercial dosage forms of flucytosine and the results were compared with those obtained by a HPLC procedure (cyano column) developed as a reference method. PMID- 1932276 TI - Liquid chromatographic separation of phenothiazines and structurally-related drugs using a beta-cyclodextrin bonded phase column. AB - The retention behaviour of 16 phenothiazines and structurally-related drugs on a beta-cyclodextrin bonded phase column is examined with respect to pH, methanol and TEAA concentrations in the mobile phase, and column temperature. The results are utilized to optimize the separation of these compounds. Both isocratic and gradient-elution separation of the 16 phenothiazine derivatives on the beta cyclodextrin bonded phase column are investigated. The successful separation of all of the compounds is achieved in the gradient-elution mode. PMID- 1932277 TI - Determination of the chromonar hydrochloride metabolite in urine using derivative spectroscopy. PMID- 1932278 TI - High-performance liquid chromatographic assay of pancreatic lipase activity. PMID- 1932279 TI - Underestimation of visual texture slant by human observers: a model. AB - The perspective image of an obliquely inclined textured surface exhibits shape and density distortions of texture elements which allow a human observer to estimate the inclination angle of the surface. However, it has been known since the work of Gibson (1950) that, in the absence of other cues, humans tend to underestimate the slant angle of the surface, particularly when the texture is perceived as being "irregular." The perspective distortions which affect texture elements also shift the projected spatial frequencies of the texture in systematic ways. Using a suitable local spectral filter to measure these frequency gradients, the inclination angle of the surface may be estimated. A computational model has been developed which performs this task using distributions of outputs from filters found to be a good description of simple cell receptive fields. However, for "irregular" textures the filter output distributions are more like those of "regular" textures at shallower angles of slant, leading the computational algorithm to underestimate the slant angle. This behavioral similarity between human and algorithm suggests the possibility that a similar visual computation is performed in cortex. PMID- 1932280 TI - A model for neural control of gradation of muscle force. AB - A mathematical muscle model is presented that relates neural control signals linearly to muscle force without violating important known physiological constraints, such as the size-principle (Henneman and Mendell 1981) and non linear twitch summation (Burke et al. 1976). This linearity implies that the neural control signals (defined as a weighted sum of activities in a nerve bundle) can be interpreted as the internal representation of total muscle force. The model allows for different relative contributions from the two force-grading mechanisms, i.e. the recruitment of motor units and the modulation of their firing frequency. It can therefore be applied to a variety of (distal and proximal) muscles. Furthermore, it permits simple mechanisms for controlling muscle force, e.g. in superposed motor tasks. The model confirms our intuitive notion that a weighted sum of activities in a nerve bundle can directly represent an external controlled variable, which in this case is exerted muscle force. PMID- 1932281 TI - A recurrent system incorporating characteristics of the visual system: a model for the function of backward neural connections in the visual system. AB - A recurrent system is constructed in order to investigate the role of the backward neural connections found in the primate visual system. The system incorporates a layer to perform localized spatial frequency analysis of input images, a function which has been assumed to take place in the primary visual cortex. The function of the system is examined by simulation. The results show that the system can separate an object pattern from its background, irrespective of its precise position. The acceptable displacement range for input images is determined from the width of the window function used to calculate the local Fourier transform. A multilayer version of the above recurrent system is also constructed. PMID- 1932282 TI - Optimising synaptic learning rules in linear associative memories. AB - Associative matrix memories with real-valued synapses have been studied in many incarnations. We consider how the signal/noise ratio for associations depends on the form of the learning rule, and we show that a covariance rule is optimal. Two other rules, which have been suggested in the neurobiology literature, are asymptotically optimal in the limit of sparse coding. The results appear to contradict a line of reasoning particularly prevalent in the physics community. It turns out that the apparent conflict is due to the adoption of different underlying models. Ironically, they perform identically at their co-incident optima. We give details of the mathematical results, and discuss some other possible derivations and definitions of the signal/noise ratio. PMID- 1932283 TI - A neural network model of the cerebellar cortex performing dynamic associations. AB - The present paper proposes a model which applies formal neural network modeling techniques to construct a theoretical representation of the cerebellar cortex and its performances in motor control. A schema that makes explicit use of propagation delays of neural signals, is introduced to describe the ability to store temporal sequences of patterns in the Golgi-granule cell system. A perceptron association is then performed on these sequences of patterns by the Purkinje cell layer. The model conforms with important biological constraints, such as the known excitatory or inhibitory nature of the various synapses. Also, as suggested by experimental evidence, the synaptic plasticity underlying the learning ability of the model, is confined to the parallel fiber--Purkinje cell synapses, and takes place under the control of the climbing fibers. The result is a neural network model, constructed according to the anatomy of the cerebellar cortex, and capable of learning and retrieval of temporal sequences of patterns. It provides a framework to represent and interpret properties of learning and control of movements by the cerebellum, and to assess the capacity of formal neural network techniques for modeling of real neural systems. PMID- 1932284 TI - Visual homing using an associative memory. AB - Homing is the process by which an autonomous system guides itself to a particular location on the basis of sensory input. In this paper, a method of visual homing using an associative memory based on a simple pattern classifier is described. Homing is accomplished without the use of an explicit world model by utilizing direct associations between learned visual patterns and system motor commands. The method is analyzed in terms of a pattern space and conditions obtained that allow the system performance to be predicted on the basis of statistical measurements on the environment. Results of experiments utilizing the method to guide a robot-mounted camera in a three-dimensional environment are presented. PMID- 1932285 TI - Color categorization and color constancy in a neural network model of V4. AB - We develop a neural network model that instantiates color constancy and color categorization in a single unified framework. Previous models achieve similar effects but ignore important biological constraints. Color constancy in this model is achieved by a new application of the double opponent cells found in the "blobs" of the visual cortex. Color categorization emerges naturally, as a consequence of processing chromatic stimuli as vectors in a four-dimensional color space. A computer simulation of this model is subjected to the classic psychophysical tests that first uncovered these phenomena, and its response matches psychophysical results very closely. PMID- 1932286 TI - In vitro characteristics of highly purified factor VIII concentrates. PMID- 1932287 TI - Ultrapure plasma factor VIII produced by anti-F VIII c immunoaffinity chromatography and solvent/detergent viral inactivation. Characterization of the Method M process and Hemofil M antihemophilic factor (human). PMID- 1932288 TI - Viral safety and inhibitor development associated with monoclonal antibody purified F VIII C. PMID- 1932289 TI - Antihemophilic factor isolated with monoclonal antibodies. PMID- 1932290 TI - Effects of factor VIII concentrates on the immune system in hemophilic patients. PMID- 1932291 TI - Clinical experience with Hemofil M in a hemophilia patient exhibiting inhibitors. PMID- 1932293 TI - In-process controls and characterization of recombinate antihemophilic factor (recombinant). PMID- 1932292 TI - Insight into the structure, function, and biosynthesis of factor VIII through recombinant DNA technology. PMID- 1932294 TI - Current status of a recombinant antihemophilic factor VIII clinical trial organized by Baxter. PMID- 1932295 TI - Acute myeloid leukemia in the elderly: biological features and search for adequate treatment. AB - AML in elderly patients is a heterogeneous disease which is characterized by a number of unfavorable features such as development, cytogenetics, blast cell differentiation, and poor treatment response. Specifically, the association between a higher incidence of unfavorable cytogenetic abnormalities in elderly patients and poor prognosis has been well documented. Low treatment response may be due to the specific biology of AML in this patient group, but also to host specific factors such as higher treatment-related morbidity and mortality. Treatment tolerance cannot be judged on grounds of chronological age alone; risk factor analysis with regard to performance status, organ function, and underlying systemic disease need to be considered as well. For effective induction treatment in elderly patients, instant and intensive chemotherapy appears to be necessary, while delayed treatment or administration of supportive care alone provide unsatisfactory results. Standard-dose ara-C/anthracycline-containing regimens are the treatment of choice in patients with good performance status. However, patients with a WHO grading of greater than 3 might rather benefit from reduced regimens such as low-dose ara-C. At present, greatest improvement of AML treatment in elderly patients can be expected from an improvement of supportive care. PMID- 1932296 TI - Apparent decrease and elimination of BCR/ABL mRNA-expressing residual cells in patients with chronic myelogenous leukemia after allogeneic bone marrow transplantation. AB - A modified two-step polymerase chain reaction (PCR) was used for the amplification of BCR/ABL mRNA in 16 patients with Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation (BMT). At different intervals after BMT, patient cells were assessed for the presence of BCR/ABL mRNA by two subsequent rounds of PCR amplification; this procedure increased the sensitivity for the detection of one Ph+ cell in 10(4-5) to one cell in 10(5-6). Eight of 16 patients were negative by two-step PCR 1-39 months after BMT, suggesting an elimination of Ph-positive cells or a decrease below the threshold of detection. Although five patients showed negative results by the one-step PCR only, they were tested positive when nested primers were used, indicating a substantial decrease in the amount of BCR/ABL target mRNA compared with earlier pre- or post-transplant analyses. One patient who was still PCR positive 27 months after BMT became negative 12 months later. Persistence of BCR/ABL mRNA-expressing cells correlated with subsequent clinical relapse only when the transplantation was performed during blast crisis. All patients who underwent transplantation in chronic phase, including those with BCR rearrangement by PCR, are in clinical and hematological remission between 24 and 95 months after BMT. We conclude that aggressive chemotherapy combined with total body irradiation is unable to completely eradicate the malignant clone in all CML patients, and it might be speculated that other mechanisms (e.g., graft versus host reaction [GVHD] or graft versus leukemia effect [GVL]) may effectively eliminate residual leukemic cells. PMID- 1932297 TI - Ceftazidime with or without amikacin for the empiric treatment of localized infections in febrile, granulocytopenic patients. AB - In a prospective randomized study, 90 granulocytopenic febrile patients presenting with a localized infection were treated empirically with ceftazidime alone or in combination with amikacin (1.5 g/day). Two thirds had received selective oral antimicrobial prophylaxis before therapy. The treatment groups were comparable in terms of the depth and duration of granulocytopenia as well the distribution of the infection categories and rate of bacteremia. There was no difference with respect to the final response: 53% for the monotherapy group versus 48% for the combination group, and both regimens appeared to be equally safe. The duration of fever, clinical symptoms, antibiotic therapy, and granulocytopenia were comparable for both treatment groups, and approximately 90% of patients survived the infection. Only one patient given monotherapy required amikacin. It is concluded that aminoglycosides are not necessary for the empiric treatment of infectious complications in granulocytopenic patients if antibacterial prophylaxis has been given beforehand. PMID- 1932298 TI - Cytogenetics of chronic myelogenous leukemia (CML) correlated to the histopathology of bone marrow biopsies. AB - Cytogenetic findings were correlated to histopathological bone marrow findings evaluated simultaneously in 103 patients with chronic myelogenous leukemia (CML). CML was subtyped histologically according to the number of megakaryocytes and increase of fibers or blasts within the bone marrow. The Philadelphia chromosome (Ph 1) was found in 88.3% of all patients (91/103). Chromosome aberrations additional to the Ph 1-chromosome were noticed in 20 of 91 (22%) cases. The additional karyotype changes occurred significantly more frequently among patients with increase of fibers in the bone marrow compared with patients without increase of fibers or blasts (p less than 0.05). Karyotype changes associated with increase of fibers in Ph 1-positive cases of CML were trisomy 8 and 19, +Ph1, t (1; 11), and i (17q). Ph 1-positive CML patients with additional karyotype changes had a significantly shorter survival (p less than 0.04) than Ph 1-positive patients without additional chromosome aberrations. Our results suggest that histopathological examination of the bone marrow should be considered in the evaluation of cytogenetic markers in chronic myeloproliferative disorders. PMID- 1932299 TI - Interferon alpha-2b in the long-term treatment of essential thrombocythemia. AB - We treated 35 patients affected with essential thrombocythemia (ET) with interferon (IFN) alpha-2b. Our treatment scheme consisted of (a) a 6-month induction phase and (b) a continuous maintenance phase. During the induction phase, our results showed that using 21 million units (mu) of IFN weekly platelet counts fell below 600 x 10(9)/1 in about 90% of patients. These data demonstrate that well-tolerated doses of IFN can rapidly correct excessive thrombocytosis. During the continuous maintenance phase, 61% of patients required 3 mu three times a week, 15% once a week, and 24% daily. Thus the minimal IFN doses able to maintain platelet count below 600 x 10(9)/l varied between 3 and 21 mu per week. During long-term treatment, subjective side effects were tolerable, especially using 3 mu three times a week. We conclude that IFN alpha-2b is an effective drug in the long-term treatment of ET. PMID- 1932300 TI - Immunoglobulin serum levels in very low birth weight infants treated with different intravenous preparations. AB - Parenteral human immunoglobulin (IVIG) administration is widely used in low birth weight (LBW) infants for prevention and therapy of neonatal infection. In previous studies, IVIG preparations containing IgG and low IgM concentrations were commonly used. In this study we compare immunoglobulin serum levels in two groups of healthy preterm infants receiving prophylactically standard IVIG (Sandoglobulin, 0.1 mg/kg IgM) or IgM-enriched IVIG (Pentaglobin, 30 mg/kg IgM). Immunoglobulin levels were assayed by rate nephelometry at birth and at 3, 5, 7, and 14 days after birth. The two groups of patients were matched for gestational age (31 +/- 2.3 weeks), birth weight (1320 +/- 340 g), and serum IgG (4.1 +/- 1.9 milligram) and IgM (0.22 +/- 0.18 milligram) levels at birth. Significantly higher IgM levels were observed at 3 and 5 days after IgM-enriched IVIG administration (p less than 0.01). Higher IgG levels were attained and persisted for 2 weeks after standard IVIG administration (p less than 0.01). These data indicate different IgG and IgM target levels in LBW infants treated with different immunoglobulin preparations. PMID- 1932301 TI - Direct in vivo biotinylation of erythrocytes as an assay for red cell survival studies. AB - Direct in vivo labeling of erythrocytes with biotin is shown as a method for estimation of red cell survival as well as of enrichment of young or aged erythrocytes. Two succinimide esters (biotin-N-hydroxysuccinimide ester [BNHS], caproylamidobiotin-N-hydroxysuccinimide ester [C-BNHS] were used for biotin labeling of erythrocytes. With improved syntheses, pure BNHS (mp, 212 degrees-214 degrees C) and the spacered intermediate for C-BNHS, 6-(biotinylamide) hexanoate (mp, 225 degrees-226 degrees C) were obtained in an overall yield of 86%; the yield of C-BNHS (mp, 167 degrees-169 degrees C) was 68%. When three doses of 1 mg C-BNHS are injected intravenously into mice at 24-h intervals, all the red cells are biotin labeled. The rate of red cell production as well as the life span of red cells can be measured without any effect on erythropoiesis or damage by red cells in vitro. The survival curve seems to be linear, with 2.5%-3.3% disappearance of biotin-labeled red cells daily. In mice, in vivo biotin labeling avoids damaging red cells by in vitro procedures and does not influence the steady state of erythropoiesis by hypertransfusion. Therefore, in vivo biotin labeling is a very useful method for determining red cell survival time in small animals. PMID- 1932302 TI - Reticulocyte counting in thalassemic and other conditions with the R-1000 Sysmex analyzer. AB - Precise reticulocyte counts are difficult to obtain by the manual method when their percentage in the blood is low or normal. In these instances, rapid reticulocyte counting by flow cytometry appears to offer more accuracy and precision. The purpose of this study was to establish reticulocyte counts in heterozygous beta-thalassemia for reference purposes and to evaluate the performance of the recently introduced apparatus R-1000 (Sysmex) in the very heterogeneous thalassemic and sickle-cell syndromes. We studied a total of 364 samples; 102 heterozygous beta-thalassemia carriers, 180 normal matched controls, 36 patients with thalassemia major or intermedia, and 46 patients with various sickle-cell syndromes. Reticulocyte counts (both as percentage and as total number) were higher in heterozygous beta-thalassemia than in normal controls (p less than 0.001) and showed an inverse correlation with the respective hemoglobin values (p less than 0.001). These results confirm the proposed slightly increased erythropoietic activity in heterozygous beta-thalassemia carriers. A drawback of the technique is that the reticulocyte-platelet discrimination error is signaled frequently in all conditions displaying a marked red cell heterogeneity, especially when these are associated with high reticulocyte numbers. This calls probably for readjustment of the corresponding algorithm. In addition, all these conditions show a significantly increased auramine-O mature red-cell nonspecific fluorescence. PMID- 1932303 TI - Immunological characterization of canine hematopoietic progenitor cells. AB - Canine hematopoietic progenitor cells were characterized by separation with monoclonal antibodies. Depleted and enriched fractions were studied for growth of CFU-GM in semisolid agar and for repopulating capacity of lethally irradiated dogs. CFU growth was not reduced by depletion of marrow using monoclonal antibodies F 3-20-7 (anti-dog Thy-1), MT606 (anti-human CD 6), and IOT2a (anti human DR). CFU growth was variable following treatment with the anti-canine T cell antibody MdT-P 1 and immunomagnetic bead separation. It was regularly enriched when MdT-P 1 treatment was followed by immunorosetting with staphylococcal protein A-loaded sheep red blood cells and density gradient separation. Lethally irradiated dogs were reconstituted by autologous marrow depleted of MdT-P 1-positive cells using immunorosetting and density gradient centrifugation, whereas immunomagnetic bead-depleted marrow was ineffective. Fluorescence-activated cell sorting showed enrichment of hematopoietic progenitor cells in the weakly MdT-P 1-positive fraction. PMID- 1932304 TI - Detection of engraftment and mixed chimerism following bone marrow transplantation using PCR amplification of a highly variable region-variable number of tandem repeats (VNTR) in the von Willebrand factor gene. AB - Detection of host cells in peripheral blood and/or bone marrow (mixed chimerism) of patients who have undergone bone marrow transplantation (BMT) is possible using either immunological methods or cytogenetic or molecular genetic analysis. We shall report a new method for the detection of mixed chimerism, which makes use of the fact, that the von Willebrand factor (vWF) gene has a highly variable region-variable number of tandem repeats (VNTR)--within intron 40. vWF-VNTR amplification by the polymerase chain reaction (PCR) was performed as described by Peake et al. We have studied 185 peripheral blood and/or bone marrow samples of 26 patients. Median time after BMT was 14 months (range 1-83 months). Of the 11 patients who were studied sequentially during the first 100 days following BMT, mixed chimerism was detected in four, but only transiently. None of these patients has relapsed so far. Of 18 patients who were studied more than 100 days after BMT mixed chimerism was found in three; two of these patients have subsequently relapsed. The advantages of this new method are: (a) it is informative in a high percentage of patients; (b) it requires only small amounts (200 microliters) of peripheral blood; (c) reliable results can be obtained at leukocyte counts of even less than 50 per microliters. The clinical relevance and sensitivity of the method compared with established methods for detection of mixed chimerism remain to be determined. PMID- 1932305 TI - Medullary histiocytosis following treatment of severe aplastic anemia with recombinant human interleukin-3 in combination with antilymphocyte globulin, cyclosporin A, and methylprednisolone. AB - This case report describes the clinical use of recombinant human interleukin-3 as adjunct to immunosuppressive therapy with antilymphocyte globulin, cyclosporin A, and methylprednisolone for refractory severe aplastic anemia. Hematopoietic response to treatment was moderate and peripheral blood counts (neutrophils, eosinophils, monocytes, reticulocytes) increased only slightly. Unexpectedly, during the time of interleukin-3 administration a substantial bone marrow infiltration by macrophages became detectable, consistent with the diagnosis of medullary histiocytosis, that may have prevented recovery of normal hematopoiesis in this patient. This observation may indicate the need for careful use of interleukin-3 in patients with drug-induced immunodeficiency. PMID- 1932306 TI - Nonsecretion of myeloma protein in spite of an increase in tumor burden by chemotherapy. AB - A unique case of IgA kappa myeloma is presented. While the myeloma cells had secreted a large quantity of IgA kappa monoclonal protein, they were induced to stop secreting the monoclonal protein by cyclophosphamide and vincristine, in spite of a remarkable increase in tumor burden. The absence of intracytoplasmic IgA kappa was clearly evidenced by the immunofluorescence technique using anti IgA and anti-kappa monoclonal antibodies. PMID- 1932307 TI - The evaluation of agreement by means of log-linear models: proxy interviews on reproductive history among floriculture workers in Colombia. AB - We used data from Colombia to compare responses from husbands and wives concerning the reproductive history of the women. We analyzed agreement in two ways: First, we compared kappa statistics between independent subgroups. Second, we evaluated agreement by means of log-linear models. Men underreported the total number of pregnancies and the number of abortions of their wives. Agreement on the term of the pregnancy was dependent on the ages of the partners. Log-linear modeling provides an attractive alternative to more usual ways of studying agreement. PMID- 1932308 TI - Hip fracture incidence and mortality in New England. AB - We used Medicare data to conduct a population-based study of osteoporotic hip fracture incidence and outcomes among New England residents. To reduce bias and improve data reliability, we combined data from multiple files; we found that 6% of cases would have been missed had we relied on hospital claims alone. Hip fracture incidence (per 1,000 person-years) increased for white females from 2.2 for ages 65-69 to 31.8 for ages 90-94 and for white males from 0.9 for ages 65-69 to 20.8 for ages 90-94. Incidence among blacks was lower in all age/sex groups. The female/male relative risk was greater among whites than among blacks. Case fatality following hip fracture was 12.5% at 90 days and 23.7% at 1 year and was higher among males, older patients, and those who had documented comorbidity or who were residents of nursing homes. PMID- 1932310 TI - A graphical approach to the interpretation of age-period-cohort data. AB - Two major obstacles to the routine application of age-period-cohort models are (1) the identification problem, and (2) the fact that separate interpretation of the coefficients of the model is seldom possible. We offer a practical solution to these obstacles that involves plotting the relation between the variable of interest and the age, period, and cohort variables in such a manner that nontrivial age, period, or cohort effects are readily recognized as particular types of features in the graph. These features remain recognizable in the presence of normal sampling variability. Examples are given for applying the technique to previously published mortality data. PMID- 1932309 TI - Suspected risk factors for depression among adults 18-44 years old. AB - We examined suspected risk factors for depression among adults ages 18-44 years. The subjects, selected by probability sampling for a multisite collaborative study, were interviewed at baseline and again at follow-up after one year. The risk of major depression was higher for women as compared with men (RR = 1.5), and for the maritally separated or divorced versus all other adults (RR = 1.9), but at lower levels for employed men and women as compared with the unemployed (RR = 0.6). Sex and marital separation or divorce also were associated with increased risk of a less specific and severe depressive syndrome; working for pay was associated with lower risk. In addition, risk of the depressive syndrome was lower for Hispanic Americans versus all other persons (RR = 0.3), and there was an important interaction of age and sex. With increasing age, women were at increasingly higher risk for the depressive syndrome, as compared with men. Finally, the risk of simple depression was higher for women than for men (RR = 1.8), but was not strongly associated with other suspected risk factors under study once sex was taken into account. PMID- 1932311 TI - Analysis of quantitative data by quantiles in epidemiologic studies: classification according to cases, noncases, or all subjects? AB - Quantitative exposure data in epidemiologic studies are frequently analyzed by ordered categories. Categorization by quantiles can be based on the distribution of (1) cases, (2) noncases, and (3) all subjects. The advantages of the three schemes in determining quantiles were compared. They were found to give the same power regarding a test for trend over a wide range of study situations. Considerations on the representativeness and the ease of the analysis implementation could dictate the choice of the categorization scheme. PMID- 1932312 TI - Lag time between stress events and risk of recurrent episodes of inflammatory bowel disease. AB - We followed a cohort of 124 subjects with a history of inflammatory bowel disease to ascertain risk estimates for clinically active disease associated with exposure to recent stress events. We calculated risk estimates for three lag models (-1, 0, + 1 month). The data indicated a strong association between stress exposures and new clinical episodes of disease (RR = 2.9, 95% Cl: 2.0-4.1), most apparent in the immediate period (lag = 0). Risk estimates were also elevated for extended episodes of disease in subjects under stress compared with unexposed subjects. These results underscore the importance of monitoring stress exposures in prevention and treatment of recurrent disease. PMID- 1932313 TI - Familial aggregation of bladder cancer stratified by smoking status. AB - To assess bladder cancer incidence in first-degree relatives of affected probands, bladder cancer patients and matched control probands provided general demographic and smoking information on their first-degree relatives. Bladder cancer incidence was established through information from the New York State Tumor Registry. The risk ratio for relatives of case probands versus relatives of control probands was 1.9; for relatives who smoked, the risk ratio was 2.1, while for nonsmoking relatives, the risk ratio was 1.8. Results from a proportional hazards regression analysis agreed with those above. These results indicate a familial component that is independent of smoking. PMID- 1932314 TI - Bilateral oophorectomy trends in Olmsted County, Minnesota, 1950-1987. AB - Over the 38-year period from 1950 through 1987, 1,434 Olmsted County, Minnesota women had a first unilateral oophorectomy, while 1,828 underwent bilateral oophorectomy (including 113 with a second unilateral oophorectomy). Most procedures (61% of unilateral and 87% of bilateral oophorectomies) were in conjunction with hysterectomy, and trends over time paralleled those reported for hysterectomy. Almost half of all operations (27% of unilateral and 63% of bilateral oophorectomies) were elective. The rise in bilateral oophorectomy rates over time (3.7 per 100,000 person-years per year, P = 0.016) was mostly due to elective procedures among older women, with both an increased frequency of surgery and a shift from unilateral to bilateral oophorectomy. PMID- 1932315 TI - Epidemiologic studies of diseases in which a necessary cause is known. PMID- 1932316 TI - Practical considerations in choosing between the case-cohort and nested case control designs. PMID- 1932317 TI - Patterns of epidemic hysteria in a school. PMID- 1932318 TI - Years of potential life lost (YPLL)--what does it measure? PMID- 1932319 TI - The Yi Migrant Study: population exposures influencing blood pressure patterns. PMID- 1932320 TI - Effect of migration on blood pressure: the Yi People Study. AB - The Yi People Study was conducted in Puge County, Sichuan Province, People's Republic of China. Four population groups were surveyed for risk factors for cardiovascular disease. Included were two groups of Yi farmers living either in a high mountainous area in extremely remote villages at or above 2,750 meters elevation, or in a mountainside area at about 1,800 meters elevation. A third study group consisted of Yi farmers who migrated to the county seat during the 1950s. Local residents of the county seat, the Han people, constituted the fourth group. Blood pressure rises very little with age after puberty in Yi farmers, but there was a trend of increasing blood pressure with age in Yi migrants and Han. Mean body mass index (kg/m2) and heart rate were higher in Yi migrants than in Yi farmers. For men, both systolic and diastolic blood pressure were greater among Yi migrants than among Yi farmers. These differences persisted after adjusting for age and body mass index. Among women, after adjusting for age, BMI, and altitude, only diastolic blood pressure was lower among Yi farmers than Yi migrants. Yi migrants and Han had similar blood pressures. In 1986, a sample of men participated in more detailed studies of diet, serum, and urine. The proportion of energy from fat ranged from less than 10% among high-mountain Yi farmers to almost 40% among Yi migrants and Han. Compared with Yi farmers, Yi migrants consumed more sodium and less potassium, calcium, and magnesium, had lower serum potassium, and a greater sodium/potassium ratio. Urinary excretion of sodium, calcium, and the sodium/potassium ratio were all greater in Yi migrants than in Yi farmers, while the reverse was seen for potassium. These data suggest that changes in life-style, including dietary changes, contribute importantly to the higher blood pressure among Yi migrants. PMID- 1932321 TI - I feel like an alcohol advertisement. PMID- 1932322 TI - Does the occupational structure of the Hunter Region explain the high rates of ischaemic heart disease among its men? AB - To compare rates of ischaemic heart disease (IHD) among men in occupation groups defined by the new Australian Standard Classification of Occupations (ASCO) and to investigate whether their high mortality rates from IHD in the Hunter Region of New South Wales (NSW) could be explained by its occupational structure, we used official death records and data from the World Health Organization MONICA Project conducted in Newcastle. The study population consisted of men aged 25 to 64 years in NSW and in the Hunter Region for whom occupational information was available. For deaths from IHD between 1984 and 1988 in NSW, indirectly standardised mortality and morbidity ratios (SMRs) were: significantly low for professionals, 66 (95% confidence interval (CI) 60-71) and managers and administrators, 79 (95% CI 74-83); intermediate for paraprofessionals (92), clerks (94) and salesmen and personal service workers (97); and significantly high for tradesmen, 113 (95% CI 107-118), labourers and related workers, 118 (95% CI 113-124) and plant and machine operators and drivers, 125 (95% CI 118-133). Broadly similar patterns were found for IHD deaths and for fatal and nonfatal myocardial infarction in the Hunter Region. When occupation- and age-specific mortality rates from IHD were used to calculate SMRs for the Hunter Region, SMRs for all ASCO groups except paraprofessionals were over 100. Mortality rates for occupational groups classified by ASCO were consistent with well-established differences associated with socioeconomic status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932323 TI - Social class, gay men and AIDS prevention. AB - The relationship between sexuality, gay communities and class is potentially a very large problem for AIDS prevention. Class is a historical process which interacts with sexuality in ways still little understood. The complexities of modern class structures need full acknowledgement; labour market groupings are internally divided, and cultural privilege and exclusion are important. A community survey in New South Wales of men who have sex with men shows the class selectiveness usual in such research. An exploration of correlates of labour market position, income and education finds few relationships with attachment to milieu except for involvement with gay organisations, and minor differences in broad measures of sexuality but some class differences in HIV risk-taking and some differences in exposure to information and in attitude. An exploration of several cases from a life-history study of working-class gay men shows the impact of class circumstance on the formation of sexual relationships and points to the accessibility of unlabelled homosexual activity in working-class milieux. Research on working-class education points to the importance of curriculum change in overcoming class exclusion, and is moving towards empowerment models of great relevance in AIDS education. PMID- 1932324 TI - Drink-driving in the general night-time driving population, Adelaide 1989. AB - A roadside breath alcohol survey was conducted by the NHMRC Road Accident Research Unit in 1989 to monitor the efficacy of random breath testing (RBT) by the police. A reduction of 40 per cent in the proportion of drivers above the legal blood alcohol limit of 0.08 g/100 ml was found to coincide with a marked increase in the level of publicity of police RBT operations. Other factors may also have contributed to these large reductions in illegal drink-driving but this result was similar to that observed in 1987 when a major increase in publicity was accompanied by an increase in the level of enforcement of RBT. Although the full effect of these reductions has diminished with time, there appears to have been a decrease in illegal drink-driving in Adelaide from 1983 to 1987 and again to 1989. PMID- 1932325 TI - Consumerism in the health care setting: an exploratory study of factors underlying the selection and evaluation of primary medical services. AB - Recent policy initiatives in Australia have continued the debate concerning the appropriate model of health care for this country. A market economy model, predicated on the existence of true consumerism, has been promoted by influential organisations to replace the current system. To test the validity of this perception and to explore the level of consumerism which exists in the Australian health care setting, we undertook a cross-sectional survey of general practitioner attenders in the outer western and northern suburbs of Sydney. Three hundred and thirty-three patients from six general practices were polled over a two-week period in March 1990. Far from demonstrating consumerist behaviour (especially the considered selection and evaluation of services), the survey population was strongly attracted to the traditional model of medical care, which is characterised by the trusting and dependent relationship of patients with their doctors. PMID- 1932326 TI - Beyond stereotypes: a study of some New Zealand women alcohol drinkers. AB - A comparison of folk categories of types of drinker and recorded alcohol consumption data, both derived from New Zealand women, with established risky levels of drinking indicates that there is some correspondence between folk categories of non-'ordinary' drinking and drinking at epidemiologically defined risky levels. However, of more importance to the majority of women drinkers, women's drinking which is completely socially acceptable and certainly regarded as quite 'ordinary', can also be at or well above risky levels. These findings are discussed in the context of the increasing normalisation of alcohol in women's lives. I argue that they support a 'reduced consumption' rather than a 'safe limits' alcohol policy. PMID- 1932327 TI - Mortality in Pacific island countries around 1980: geopolitical, socioeconomic, demographic and health service factors. AB - Inhabitants of Pacific island countries experience a wide range of levels and cause structures of mortality. Data on socioeconomic, geopolitical and demographic variables have been analysed here to identify correlates and determinants of mortality in Pacific island countries circa 1980. The mortality data used in the study were the best available for the period and are reasonably accurate; descriptive data were derived from recognised sources. Political status was a major correlate, with independence positively associated with mortality. However, the influence of political status was partly accounted for by economic and social variables. Economic indices, particularly imports per capita, were major inverse correlates of mortality. Disparities in life expectancy occurred between malarious and nonmalarious countries, and these were not explicable by other factors. Melanesians, especially women, experienced high mortality rates. Education and doctor availability were both associated with increased life expectancy. Intercorrelation and confounding need to be taken into account in the interpretation of this analysis. The results have ramifications for policy development in the Pacific island countries themselves, and for investment and aid programs from major donor nations and organisations. PMID- 1932328 TI - Assessing the residential care needs of nursing home applicants. AB - In a study of nursing home applicants, residential care decisions made by a multidisciplinary assessment team were examined. The team agreed that of the 296 applicants assessed, 54 per cent required the high level of physical and supportive care provided in a nursing home. Hostel care was recommended for 17 per cent, continuing care at home for 17 per cent, hospice care for 1 subject, and in 13 per cent of cases the team postponed their decision. A decision for nursing home care was associated with low Barthel Index of Activities of Daily Living scores, dementia, incontinence and the absence of a carer willing to continue care. A decision to delay was associated, in most cases, with a requirement for further in-patient assessment and/or rehabilitation, and therefore with a potential for functional improvement. A decision for hostel care instead of home care was associated with a low level of informal support and the absence of a carer who was a spouse or daughter. The findings suggest that a program of geriatric assessment will accurately identify the differing care needs of nursing home applicants. The initial value of such an assessment program may be to contribute to the planning of residential and other long-term care services rather than to reduce inappropriate nursing home admissions. PMID- 1932329 TI - Protecting human research from an invasion of privacy: the unintended results of the Commonwealth Privacy Act 1988. AB - In accordance with the Privacy Act 1988 (Cth), interium guidelines for the protection of privacy in the conduct of medical research have been issued by the National Health and Medical Research Council (NHMRC) with the approval of the Privacy Commissioner. The guidelines are intended to ensure that the privacy of the individual is not interfered with when a researcher seeks the release of personal information held by a Commonwealth agency, or when a Commonwealth agency conducts medical research, and to ensure that the conduct of medical research is not inhibited by the privacy legislation. However, the procedures established by the guidelines and the responsibilities placed upon researchers and institutional ethics committees could themselves have the effect of inhibiting research. In considering amendment, NHMRC and the Privacy Commissioner are urged to produce final guidelines which do not act as the straw to break the back of the current system of institutional ethics committees, which seeks to ensure proper ethical scrutiny and the facilitation of human research. PMID- 1932330 TI - A feasibility study of organised cervical screening in southern New Zealand. AB - The 1985 electoral roll was used as a register to invite 1013 women to participate in a screening program. Appointment times and a choice of venues for having a smear were not provided. Overall, 26 per cent of the women sent invitations registered with the program. After adjustment for the prevalence of hysterectomy, the proportion who registered with the program was about 32 per cent. The low level of registration and difficulties experienced in tracing registrants and nonregistrants over time using the electoral roll resulted in the cessation of the program after 3 years. An assessment of the original invitation was made using a small case-control study, and associations between the screening history stated at interview and screening over the duration of the program were examined in nonregistrants. PMID- 1932331 TI - Cost efficiency of neonatal nurseries: the significance of unit size. AB - The cost of neonatal intensive care is high, and human and financial resources are finite. It is therefore essential to provide such care efficiently in terms of costs while still maintaining standards of care. We looked at the relationship of unit size to cost and determined the optimum and minimum size of the unit in terms of cost efficiency. Our data suggest that units with fewer than 6 ventilator cots were less cost-efficient than those with more cots while those with 12 ventilator cots were the most efficient. The calculations were done only up to 16 ventilator cots. Similarly, level II units were most cost-efficient when attached to an intensive care unit and had over 16 cots. PMID- 1932332 TI - The lung cancer epidemic in Australia, 1910 to 1989. AB - Deaths that occurred in Australia between 1985 and 1989 that were ascribed to cancers of the respiratory tract and intrathoracic organs were obtained to update Australian lung cancer mortality trends. The age-standardised mortality rate from lung cancer in males decreased significantly from 49/100,000 in 1980-1984 to 46.4/100,000 in 1985-1989 (-5.5%). Lung cancer mortality in females increased significantly to 12.3/100,000 in 1985-1989 from an average of 10.7/100,000 in 1980-1984 (+15%). We conclude that lung cancer mortality in males is declining and although mortality in females continues to increase, there is evidence that the rate of increase has started to slow. The decline in male mortality has been anticipated from their trends in smoking cessation. The slowing increase in women cannot be ascribed to similar patterns of cessation. It is considered more likely to be due to decreasing trends in tar consumption linked to the tar content of preferred brands. PMID- 1932333 TI - The road toll and the recession. PMID- 1932334 TI - Growth and differentiation of myogenic clones from adult human muscle cell cultures. AB - Clonal cultures only recently have been applied to normal and pathological human muscle, but detailed clonal analysis and differentiative properties of individual long term muscle subclones derived from adult normal human muscle cell (HMC) cultures have not been reported. In this study we compared the growth potential by plating efficiency (PE), muscle colony differentiation (MC) and growth cuvers and the differentiative properties by fusion index, dystrophin localization, creatine kinase (CK) total activity and isozyme electrophoresis in HMC cultures derived myogenic subclones. These properties were tested in two experimental culture systems (200 cells/dish versus single cell/well) and with two tissue culture media (standard medium--MM--versus conditioned medium--CM). We found a significant high PE and MC in clonal cells established with single cell/well and grown in conditioned medium. In derived subclones we observed two classes of myogenic cells: one characterized by exponential growth kinetic, branched myotubes with high fusion index and predominantly sarcolemmal distribution of dystrophin and MM band at CK electrophoresis; the other with flat growth curve, low fusion index and low CK total activity. These findings demonstrate the variability of the expression of myogenic potentials in cells cloned from adult normal HMC cultures and represent an important tool for comparing the various cell types present in normal and diseased human muscle and for transplantation of normal myoblasts in Duchenne Muscular Dystrophy. PMID- 1932335 TI - Cytometric environments: from nucleus to tissues. Proceedings of the VIII national meeting of the Italian Cytometry Group. Urbino, 12-14 September 1991. PMID- 1932336 TI - [Heterogeneity of tyrosinases isolated from rat skin, normal human skin, and human melanoma tumors]. AB - An electrophoretically homogeneous preparation of tyrosinase (Mr = 61 kDa) was isolated from rat skin. The purification procedure which consisted in chromatographic separation of Triton X-100-solubilized proteins included four main steps, namely: gel filtration, anion-exchange chromatography and two consecutive affinity chromatography steps. Isoelectrofocusing revealed the presence of 9 isoforms possessing an L-DOPA oxidase activity, of which proteins with pI of 4.26 and 4.33 were the major ones. The specific activity of the preparation was 43 nmol/min/mg of protein. Human skin epidermis was practically devoid of the L-DOPA-oxidase activity which was due not only to the absence of tyrosinase but also to the presence of a large amount of a 66 kDa protein able to inhibit the oxidation of L-DOPA to DOPA-chrom. The tyrosinase preparation from human melanoma consisted, predominantly, of two isoforms (48 and 69 kDa) which upon isoelectrofocusing displayed a high heterogeneity at pH around 3-5. The specific activity of the melanoma preparation markedly exceeded that of normal skin tyrosinase and was equal to 290 nmol/min/mg of protein. PMID- 1932337 TI - [Uncoupling of oxidative phosphorylation by fatty acids and detergents suppressed by ATP/ADP antiporter inhibitors]. AB - The effects of ATP/ADP-antiporter inhibitors on the uncoupling of oxidative phosphorylation by palmitic acid, detergents and protonophore FCCP in liver mitochondria were studied. The uncoupling activity of these compounds was estimated by their stimulating effect on succinate oxidation and H+ conductivity of the inner mitochondrial membrane in the presence of oligomycin. Carboxyatractylate and pyridoxal 5-phosphate suppressed the uncoupling effects of palmitic acid and anionic detergents but had no effect on the uncoupling action of the nonionic detergent Triton X-100, the cationic detergent CTAB and FCCP. The data obtained are discussed in terms of the putative role of the ATP/ADP antiporter in the electrophoretic transport of hydrophobic anions from the mitochondria. PMID- 1932338 TI - [Comparative study of lymph node gangliosides and blood serum of normal and T lymphotrophic baboons]. AB - The gangliosides from the lymph nodes and blood sera of normal and T-lymphomic baboons were studied. In lymph nodes the major gangliosides were identified as GM3 and GD3, those in blood sera--as GM3, GM1 and GD3. Gangliosides GM3 and GD3 contained N-acetyl as well as N-glycoloyl neuraminic acids. In gangliosides isolated from lymph nodes and blood sera of T-lymphomic baboons the levels of N glycoloyl neuraminic acid markedly exceeded that in normal tissues. In tumour lymph nodes the GM3/GD3 ratio was shifted towards GD3. PMID- 1932340 TI - [Enzymes metabolizing xenobiotics in spontaneous tumors in mice]. AB - The microsomal monooxygenase activity in spontaneous mouse hepatomas has been studied. The cytochrome P-450 level in hepatomas was shown to be 2 times as low as that in the liver. The reduction of the cytochrome P-450 content in the tumour was accompanied by a decrease in the activity of benz(a)pyrene hydroxylase, amino pyrene-N-demethylase and p-nitroanisole-O-demethylase. However, 7-ethoxycoumarin O-deethylase activity in hepatomas was much higher than in the liver both estimated as mg of the microsomal protein and nmol of cytochrome P-450. The cytochrome b5 content in the hepatomas was comparable with its level in the liver. A more elevated content of NADPH-cytochrome c reductase and microsomal epoxide hydrolase activity was found in the hepatomas. The results obtained provide evidence of different oxidation effects regarding some substrates in the liver and hepatomas. The ratio of cytochrome P-450 isoforms is likely to change in the hepatomas in contrast with that in the liver. PMID- 1932339 TI - [Study of rabbit IgG, modified with carboxycarbonic anhydride of diethylenetriaminopentacetic acid]. AB - The affinity-purified by chromatography on immobilized antigen rabbit IgG was modified with mixed carboxycarbonic anhydride of DTPA which markedly alters the interaction of charged residues in the protein molecule. To study the correlation between the antigen binding activity and the conformational mobility of IgG, the reactivity of modified IgG towards conformational probes targeted at variable and constant IgG domains, was investigated. The antibody against CH2 domains of IgG, staphylococcal protein A and protein antigen ferritin were used as conformational probes. It was found that modification of IgG amino groups entails the global increase in conformational mobility involving the Fab fragments, CH2 and, probably, the CH3 domains of the Fc portion of IgG. Taking advantage of Fab fragments modification it was shown that two processes contribute to the global increase in the conformational mobility of IgG. These processes are: i) stimulation of segmental flexibility and, ii) increase in the mobility within the Fv domains of the Fab fragments. PMID- 1932341 TI - [Preparation of hexokinase isoenzyme II with expressed adsorption properties]. AB - The isolation of the native hexokinase isozyme II possessing a high adsorptive capacity is described. This property underlies the adsorption mechanism responsible for the control of the hexokinase activity in the cell and is realized only under conditions of the structural integrity of the enzyme. The latter is due, primarily, to the functional state of the specific adsorption domain which provides the specific interaction of hexokinase isozyme II with biological membranes. The criteria of nativity of skeletal muscle hexokinase were elaborated. A procedure for obtaining highly purified native hexokinase isozyme II from rat skeletal muscle was developed. PMID- 1932342 TI - [Lipoxins: study of various biosynthesis pathways]. AB - Lipoxins A4 and B4 were obtained by using soybean lipoxygenase and blood cells as a source of enzymatic activity. The conditions facilitating lipoxin biosynthesis from arachidonic acid catalyzed by soybean 15-lipoxygenase were selected. A comparative analysis of lipoxin biosynthesis with the use of cell suspensions containing only granulocytes and of mixed suspensions (platelets + granulocytes and platelets + total fraction of blood leucocytes) was carried out. PMID- 1932343 TI - [1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine: acetylhydrolase is associated primarily with low density lipoproteins in human blood]. AB - The distribution of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine: acetyl hydrolase acetyl hydrolase activity between different types of human plasma lipoproteins was studied. It was found that lipoprotein-depleted plasma is practically devoid of acetyl hydrolase and of almost all acetyl hydrolase activities recovered in the plasma lipoprotein fraction. Among different types of plasma lipoproteins the bulk of acetyl hydrolase is bound to low density lipoproteins; of those not more than 5-10% is associated with high density lipoproteins. Isolated plasma high density lipoproteins do not influence the activity of acetyl hydrolase associated with low density lipoproteins. It is suggested that low and high density lipoprotein acetyl hydrolase may play different functional roles in human plasma. PMID- 1932344 TI - [Microtubule-associated proteins]. AB - Microtubules are the key elements of the cytoskeleton responsible for cytoplasm organization and intracellular transport. Their functions are realized mainly via microtubule associated proteins (MAP), the minor components bound to the microtubule core. Among MAP there are so-called structural proteins which control tubulin polymerization and provide the "static" interaction of microtubules with other intracellular components and translocator proteins. The latter are capable of moving the material along microtubules; this process is coupled with ATP hydrolysis. The first section summarizes the data on the composition and changes during ontogenesis and functioning, such as influences on tubulin polymerization and promotion of interactions between individual microtubules, between microtubules and microfilaments and neurofilaments as well as between microtubules and membrane organelles (lysosomes, golgi stacks, mitochondria). The second section deals with the description of translocators. The biochemical properties of the following proteins are considered: i) kinesin, the protein translocating particles to the distal end of microtubules and, ii) dynein which promotes translocation in the opposite direction. PMID- 1932345 TI - [Thioredoxin: structure, properties, function]. AB - Thioredoxin, a disulfide-containing protein having a highly conservative structure, is present in all types of organisms that are phylogenetically distant from one another. The protein possesses unique capabilities and is universal in respect of physiological functions it performs. In particular, this protein participates in nucleic acid metabolism and thus may protect cells against the lethal influence of gamma-irradiation. PMID- 1932346 TI - [Oxidative modification of cytochrome P-450 during its function. I. Comparative study of the inactivation of cytochrome P-450 LM2 in various systems]. AB - The changes in the content of purified isolated cytochrome P-450 LM2 under the action of hydrogen peroxide and during its operation in a soluble reconstituted system were studied. It was found that cytochrome P-450 LM2 inactivation by hydrogen peroxide is accompanied by a decrease in the hemoprotein activity, loss of heme, oxidation of SH-groups and changes in the oligomeric state of the enzyme. There were some differences in the mechanisms of cytochrome P-450 LM2 inactivation under the action of H2O2 and during catalysis. PMID- 1932347 TI - [Oxidative modification of cytochrome P-450 during its function. II. Study of the mechanism of cytochrome P-450 LM2 inactivation in a soluble reconstructed monooxygenase system]. AB - Inactivation of cytochrome P-450 LM2 induced by hydrogen peroxide formed in the active site of the enzyme was studied. Catalase did not protect cytochrome P-450 LM2 from inactivation during its operation in a soluble reconstituted system. The hemoprotein inactivation in this system was found to depend on the ratio of hemo- to flavoproteins. It was demonstrated that cytochrome P-450 LM2 inactivation during catalysis is accompanied by cleavage of the hemoprotein molecule. It is probable that this fact plays a key role in regulation of enzyme decay. PMID- 1932348 TI - [Interaction of cells from murine organs with liposomes of various composition]. AB - The distribution of liposomes prepared from total mouse liver lipids and containing (3H)-labelled platelet activation factor in mouse organs was studied. It was shown that the majority of intraperitoneally injected liposomes prepared from total mouse liver lipids were transported to mouse liver and spleen. The interaction of liposomes with spleen cells in vitro revealed that the affinity of liposomes prepared from total spleen macrophage or total spleen lymphocyte lipids for mouse spleen cells was much higher than that of liposomes prepared from a model lipid mixture. The liposome binding to isolated spleen macrophages or lymphocytes was much higher than the liposome uptake by these cells in the total population of mouse spleen cells. PMID- 1932350 TI - [Glycosidase activity in phenotypically different pathologic lymphoid cells, found at various stages of differentiation]. AB - The activities of seven glycosidases (six lysosomal and one cytosolic) were determined in B- and T-lymphoid cells differing by immunological phenotypes and occurring at various differentiation stages. The cells were isolated from the circulating blood, bone marrow or spleens of patients with various forms of lymphoproliferative disorders. The glycosidase activities varied significantly depending on the phenotype. The highest activity of all glycosidases was observed in cells with a common lymphoid cell progenitor phenotype. In cells having the phenotype of mature T- and B-cells the glycosidase activities were comparatively low. The changes in all glycosidase activities depending on the phenotype and differentiation stage usually occurred in the same direction; however, the degree of elevation or decline of activities of individual glycosidases was different. The activities of N-acetyl-beta-D-hexosaminidase and alpha-D-mannosidase changed dramatically, whereas the changes in the activity of cytosolic neutral alpha-D glucosidase were less apparent. These data suggest that lysosomal glycosidases play specific roles in lymphoid cell differentiation. PMID- 1932349 TI - [Proteins of the lupin family, binding molybdenum, tungsten, and radionuclide effluents from the Chernobyl Atomic Energy Station]. AB - Yellow lupine seeds were found to contain two proteins and a low molecular weight fraction possessing the ability to bind Mo, W and radionuclides from the Chernobyl nuclear power in vivo and the 185W isotope in vitro. These proteins differ in their electrophoretic mobility. The electrophoretically less mobile protein undergoes proteolytic degradation; the proteolytic product retains the ability to accumulate microelements. PMID- 1932351 TI - [Growth inhibiting effect of glucocorticoids and progestins on tumor cells in vitro: effect on the rate of phospholipid reversal]. AB - The growth-inhibiting effect of dexamethasone was estimated by the ability of the hormone to inhibit the proliferative activity of in vitro cultured hepatoma 22 cells. The effect of another steroid proliferation inhibitor, progesterone, was studied in primary cell cultures of human uterine carcinoma. The cytostatic effect of dexamethasone was observed only in slowly proliferating cells and was rapidly reversed by stimulation of cell division with fresh sera. Dexamethasone did not induce any conspicuous changes in the rate of 32P incorporation into hepatoma phospholipids. In 9 out of 14 human uterine carcinomas progesterone inhibited, whereas 17 beta-estradiol stimulated the 32P incorporation into phospholipids (phosphatidylinositol and phosphatidylcholine); this effect was manifested already after 15-min incubation of cells with the hormone. The resistance of uterine carcinoma cells to steroids was paralleled, as a rule, with the increase in the basal level of 32P incorporation into the phospholipids typical of actively proliferating cells. It was assumed that the inhibition of phospholipid exchange rate is related to the earliest manifestations of the growth-inhibiting effect of steroid hormones, at least progestins. In its turn, stimulation of the proliferative activity of cells may relieve this effect of steroids, eventually resulting in a temporary decrease of the cell sensitivity to hormones. PMID- 1932352 TI - [The role of peritoneal macrophages in realizing the growth inhibiting effect of glucocorticoids on reinoculated murine hepatoma 22 cells: the effect of hydrocortisone on the cytotoxic activity and metabolism of phospholipids by macrophages]. AB - A single injection of hydrocortisone to rats with ascite hepatoma 22 had practically no effect on tumour growth. Inhibition of tumour growth was observed only after reinoculation of ascite hepatoma to mice that had received no less than 8 daily injections of the hormone. A single injection of hydrocortisone induced inhibition of the cytotoxic activity and decreased phospholipid metabolism in peritoneal macrophages. Contrariwise, long-term administration of the hormone caused marked activation of macrophage cytotoxicity. In this case incorporation of 32P into macrophage phospholipids was restored up to the control level. It is concluded that one of mechanisms underlying the inhibitory effect of glucocorticoids on macrophages is inhibition of phospholipid turnover. Presumably, long-term administration of the hormone promotes the formation of a new population of macrophages insensitive to the inhibitory effect of glucocorticoids and possessing a high cytostatic activity. The appearance of such activated macrophages may account for the enhancement of hydrocortisone effect on tumour cells upon prolonged administration of the hormone. PMID- 1932353 TI - [Intracellular L-aspartate-beta-decarboxylase of Pseudomonas sp. and Alcaligenes sp. and its immobilization]. AB - Intracellular L-aspartate-beta-decarboxylase of Pseudomonas sp. and Alcaligenes sp. was isolated, purified and characterized. The cells were destroyed by ultrasonic treatment; the enzymes were precipitated by ammonium sulfate fractionation, dialyzed and lyophylized using Biogel P-150. After gel electrophoresis homogeneous enzyme preparations were obtained. The activity of L aspartate-beta-decarboxylase is rather high--up to 92.1 U/min/mg of protein and is maximal at pH 5.5 and at temperatures of 45-55 degrees C. The Km and Vmax values for the Pseudomonas sp. enzyme are 0.1 M and 0.33 mM/min, respectively: those for the Alcaligenes sp. enzyme are 0.15 M and 1.0 mM/min, respectively. The results of amino acid analysis suggest that the enzymes slightly differ from one another with regard to aspartic and glutamic acid, alanine, valine and isoleucine content. Immobilization of the enzymes on various carriers was performed. PMID- 1932354 TI - [Features of photochemical properties of hemoglobin under native conditions]. AB - The photochemistry of human hemoglobin (Hb) in the blood and blood serum (lambda = 254-578 nm) was studied, using spectrophotometric methods. The Hb photochemistry is a complex set of photoreactions leading to successive photoconversions of Hb forms: from oxy- to met- to deoxy- and, finally, to carboxy-form. The photodestruction of Hb and the photoreactions involving other serum proteins were found to occur simultaneously. In the blood Hb photomodifications are localized directly in erythrocytes. The conditions necessary for the photo--induced rupture of erythrocyte membranes and the subsequent release of Hb into the blood plasma, were determined. Although the general characteristics of Hb photochemistry are the same for model systems and for native conditions, there are some distinctions in the effectiveness of the photoconversion. It seems likely that the observed effects are due to the antioxidant properties of the serum. These properties may be the cause of the inhibition of blood photohemolysis upon irradiation (lambda greater than or equal to 300 nm). PMID- 1932355 TI - Feasibility and reproducibility of the [3H]-thymidine labelling index in breast cancer. The SICCAB Group for Quality Control of Cell Kinetic Determination. AB - For several malignancies, autoradiographic evaluation of the S phase cell fraction by means of [3H]-thymidine ([3H]dT) has proved a valid prognostic tool which should be included in a 'risk factor profile system' to estimate prognosis in individual patients. However, its clinical implementation requires a methodological standardization, a high feasibility and an assessment of the reproducibility of results, within and between different laboratories. The recent availability of a kit for in vitro incubation with [3H]dT and histological fixation of solid tumour specimens has contributed to the methodological simplification and standardization of the technical procedure, increasing its feasibility in several institutions. For breast cancer, preliminary results from a quality control study promoted by the Italian Society of Basic and Applied Cell Kinetics (SICCAB) showed a high inter-observer reproducibility within (r = 0.96) and between different laboratories (r = 0.93). Moreover, on a series of 20 autoradiographic samples sent to 15 different institutions, only 2% of tumours shifted from one of the cell kinetic subgroups, defined using the median [3H]dT labelling index (LI) of 2.8% as a cutoff, to the other. In addition, a marked consistency of results was observed among the different Italian institutions involved in cell kinetic studies on breast cancers, both in terms of median [3H]dT LI values and basic correlations. Periodic assessment of the reproducibility of [3H]dT LI evaluation among different laboratories is needed, especially for institutions involved in multicentre clinical protocols based on cell kinetic characteristics. PMID- 1932356 TI - Cell cycle status of stromal cells in long-term haematopoietic cultures. AB - This study was performed to further define the mechanism by which the stromal micro-environment regulates haematopoiesis. In long-term marrow cultures the interactions between stromal cells and haematopoietic cells can be investigated at the cellular level. Long-term marrow cultures from hamsters do not require repopulation or addition of hydrocortisone and are suitable for investigation of cell kinetics. The cellular kinetics of haematopoietic and stromal cells, as studied by tritiated thymidine ([3H]dT) incorporation, revealed that DNA synthesis occurred in both the non-adherent and the adherent cells. In established cultures the adherent stromal cells were predominantly in a quiescent non-cycling state: less than 2% adherent cells incorporated [3H]dT within 5 h. Removal of the supernatant cells did not affect the labelling index of adherent cells, since the labelling indices at the 50-75 h time point were 14.3% and 12.5% in the presence and absence of supernatant cells respectively. An apparent stimulus for stromal cells to incorporate [3H]dT was attachment or adhesion. Following replating of supernatant cells of long-term marrow cultures, 23.3% of the reformed adherent layer cells were labelled compared with 12-14% in cultures with previously formed unmobilized adherent cells (P less than 0.01). The data indicate that adherent cells are not required to synthesize DNA for maintenance of haematopoiesis in established long-term marrow cultures, and that recruitment into the cell cycle has an independent mechanism that is not influenced by feed back from the supernatant cells. PMID- 1932357 TI - Automatic classification of cells in cell cycle phases based on Ki-67 antigen quantification by fluorescence microscopy. AB - Ki-67 antigen is thought to be a marker of cell proliferation, as it can be detected in cycling cells, i.e. cells in G1, S, G2 and M phases, but not in resting cells. The immunocytochemical staining pattern obtained by the Ki-67 monoclonal antibody varies, depending on the cell cycle phases. Analysis of double staining of Ki-67 antigen and DNA in the MCF-7 cell line by videomicrofluorometry allows the description of both the level and the pattern of Ki-67 staining in the form of a set of parameters defining each cell. These parameters were measured in MCF-7 cell populations characterized according to their position in the cell cycle. They were submitted to a statistical analysis (principal component and discriminant analysis) which allowed the determination of the optimal parameters to characterize a given cellular group and permitted the use of these parameters for an automatic classification of cells in the different cell cycle phases. In G1, S, G2, prophase + metaphase and anaphase + telophase cells, these parameters allowed a classification of cells with a good classification rate of 94.37%. A comparison of this method with methods based on the DNA histogram and bromodeoxyuridine uptake was performed. The classification coefficients stemming from the discriminant analysis were introduced into a program to obtain, automatically, the Ki-67 labelling index and the percentages of cells in each phase. This method, which allows a quick evaluation of the proliferation and the phase indices, may be more widely applicable. PMID- 1932358 TI - Loosening of cell cycle controls of human lymphocytes under the action of tumour promoter TPA. AB - The effect of tumour promoter TPA (12-O-tetradecanoylphorbol-13-acetate) on the cell cycle of human peripheral blood lymphocytes stimulated by phytohaemagglutinin (PHA) in vitro was studied and it was found that TPA caused cells to accumulate in all the cell cycle phases. This accumulation took place preferentially at later culture passages, when lymphocytes stimulated by PHA alone stopped mainly in G0/G1 phases. Other effects of TPA were cell induction to enter higher DNA ploidy and to survive and even synthesize DNA under colchicine block of mitosis or under cytochalasin block of cytokinesis. In addition, in experiments in which a transitory block through the G1 phase of cell cycle was applied with use of aminopterin, we could show that a fraction of TPA-treated cells still entered the active phase of DNA synthesis. These findings suggest that TPA causes cell cycle controls to become loose, thereby enhancing adaptability of human lymphocytes to various hindrances in the course of cell cycle and eventually causing them to acquire characteristics known to be common for tumour cells. PMID- 1932359 TI - Stimulator of proliferation of spleen colony-forming cells in T-cell deprived mice treated with cyclophosphamide or irradiation. AB - A role for T-cells in the regulation of CFU-S proliferation was investigated by determining the presence and activity of CFU-S proliferation stimulator (CFU-S stimulator) in adult mouse bone marrow after irradiation or cyclophosphamide (Cy) treatment. CBA mice previously deprived of T-cells by thymectomy, irradiation and bone marrow reconstitution (TIR) were thereafter treated with 4.5 Gy irradiation or 200 mg/kg Cy. Regenerating bone marrow cells of TIR and corresponding control mice after irradiation or Cy treatment produced CFU-S stimulator. The dose dependent increase in cytosine arabinoside cell death of normal bone marrow day 8 CFU-S was found when both CFU-S stimulators obtained after irradiation of TIR or corresponding control animals were tested. CFU-S stimulator activity in the bone marrow of TIR-Cy treated mice was also detected, but the effect was not dose dependent. This was not related to the presence of an inhibitor of CFU-S proliferation. It appears that the CFU-S stimulator activity is not related to IL 6, IL-1 or IL-2, or to an inhibitor of IL-6 or IL-1 activity. The results demonstrate the existence of CFU-S proliferation stimulator unrelated to the two major monokines in the bone marrow of immunosuppressed mice. PMID- 1932360 TI - Measurement of cell proliferation by enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody to bromodeoxyuridine. AB - An ELISA was developed and optimized to measure cell proliferation using a monoclonal antibody to bromodeoxyuridine (BrdUrd). Incorporation of BrdUrd into myoblast monolayers, measured as the optical density at 492 nm, increased in response to fetal calf serum, IGF-I and EGF, the ELISA data correlated closely with data obtained by BrdUrd immunocytochemistry (r = 0.984), cell counting (r = 0.972) and tritiated thymidine uptake by liquid scintillation counting (r = 0.990). The BrdUrd ELISA is a useful alternative to measurement of tritiated thymidine uptake by scintillation counting, and has the added advantages of dispensing with the use of radioactivity and of being less labour intensive. PMID- 1932361 TI - Mean and variance rules are more powerful or selective than quality control rules based on individual values. AB - Quality control rules based on individual values are compared with mean and variance rules using theoretical computations and simulations. Simple (1(3)s) and combined individual value rules, e. g. a 1(3)s/2(2)s/4(1)s/6 means rule, are all less powerful for detection of shifts of location than a mean rule, given identical type I errors. The mean rule is also more robust towards non-normality of data distributions. In most cases, the variance rule has more power towards increased scatter than individual value rules, and it always has the highest selectivity. Thus, the simple computations that are required for derivation of the mean and variance result in increased power or selectivity. In particular, in the computerization of quality control, the traditional mean and variance rules are preferable to more or less complicated "multi-rules" proposed for computerized quality control. PMID- 1932362 TI - Effects of dietary cholesterol and fasting on hamster plasma lipoprotein lipids. AB - Hamsters are commonly utilized for comparative study of cholesterol metabolism. The present study was conducted to assess the effects of fasting on the plasma lipoprotein cholesterol concentrations of hamsters. Over a period of 3 weeks, adult male Golden Syrian hamsters (n = 32) were fed chow with or without the addition of 2 g/kg cholesterol. Half of the animals consuming each diet were fasted for 18 hours prior to blood sampling. Comparison of diets showed the following increases in those animals receiving cholesterol: total plasma cholesterol (180%) and triacylglycerols (75%), high density (75%), low density (250%), and very low density (560%) lipoprotein cholesterol. Compared with fasted animals, total plasma triacylglycerols were higher in both non-fasted diet groups. Compared with fasted hamsters that had received cholesterol, total plasma cholesterol (mean +/- SE mmol/l) was greater (6.36 +/- 0.18 vs 5.43 +/- 0.21; p less than or equal to 0.05) in the non-fasted group, due primarily to higher VLDL cholesterol (2.07 +/- 0.18 vs 1.58 +/- 0.18; p less than or equal to 0.05). There were no differences in HDL cholesterol (2.07 +/- 0.05 vs 2.17 +/- 0.08) or LDL cholesterol (1.29 +/- 0.08 vs 1.37 +/- 0.05) between fasted and non-fasted hamsters fed cholesterol. Fasting is not necessary for the study of the plasma HDL cholesterol and LDL cholesterol of hamsters fed cholesterol. PMID- 1932363 TI - Clinical chemistry and regulatory toxicology. PMID- 1932364 TI - International Federation of Clinical Chemistry, Scientific Division Committee on Enzymes: approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. Part 7. IFCC method for creatine kinase (ATP: creatine N-phosphotransferase, EC 2.7.3.2). PMID- 1932365 TI - Twenty-five years of clinical chemistry 1964-1989. Challenges, progress and pitfalls. AB - The 25th anniversary of the founding of the German Society for Clinical Chemistry is cause for reflection on the scientific development of clinical chemistry as a discipline within the field of medicine. It also provides an opportunity to review the aims of the Society's activities over the next decade, and to present some ideas for consideration. The founding of the German Society for Clinical Chemistry and the situation that led up to it is discussed. Challenges confronting laboratory directors at the time of the founding of the Society are described, and the chronological and logical development of the three pillars of clinical chemistry out of these challenges is outlined: general clinical chemistry, analytical chemistry in the biological matrix, clinical or pathological biochemistry. Finally, the mistakes of the last 25 years and continuing dangers are critically addressed, and the good prospects of meeting the challenges that lie ahead are discussed. PMID- 1932366 TI - Evidence that interleukin-1 and lipoxygenase metabolites mediate the lethal effect of complete Freund's adjuvant in adrenalectomized rats. AB - Injection of complete Freund's adjuvant (CFA) into the right hind paw of adrenalectomized (ADX) rats caused a lethal effect, maximal after 3 days. Treatment of animals with polyclonal sera raised against either murine recombinant (mr) IL-1 alpha or mrIL-1 beta gave significant protection, suggesting the involvement of this cytokine in the observed lethality. Death was also caused by the intravenous injection of human recombinant (hr) IL-1 beta in ADX rats. No lethality was induced by either CFA or hrIL-1 beta in sham-operated (SHO) rats. The administration of dexamethasone or the dural cyclooxygenase/lipoxygenase inhibitor BW 755c significantly protected against the lethality induced by both CFA and hrIL-1 beta. The cyclooxygenase inhibitors, indomethacin and acetylsalicyclic acid, were ineffective. WEB 2086, a PAF-acether receptor antagonist, gave partial but not significant protection. These results suggest that activation of arachidonic acid metabolism is involved in the observed lethality, with lipoxygenase metabolites as possible final effectors. These experimental models of lethalities may be useful for the in vivo evaluation of drugs interfering with the synthesis and/or biological effects of IL-1. PMID- 1932367 TI - Elevation of interleukin-8 (IL-8) levels in joint fluids of patients with rheumatoid arthritis and the induction by IL-8 of leukocyte infiltration and synovitis in rabbit joints. AB - Increased amounts of interleukin-8 (IL-8) were detected in synovial fluids of patients with active rheumatoid arthritis (RA) by radioimmunoassay (RIA). The concentration of IL-8 correlated directly with the number of infiltrating neutrophils in synovial fluids. To elucidate the role of IL-8 in neutrophil accumulation at the site of synovitis, the in vivo effects of intraarticular injection of recombinant IL-8 (rIL-8) on leukocytes infiltration into the joint space and synovium were examined. Following a single injection of rIL-8 into the knee joint space of rabbits, redness of the joint and limp became apparent after 4 h and were associated with the rapid infiltration of neutrophilic leukocytes into the joint space and synovial tissues. These effects were time dependent, first becoming evident at 1 h and reaching a plateau in 4 h, and also dose dependent, with a minimal effect being elicited by 100 ng per joint. Although neutrophils were present in the greatest number at 4 h, subsequently mononuclear cells accumulated and became apparent in considerable number after 8 h. Synovial lining cells became ovoid, pleomorphic, and multilayered at 24 h. IL-8 had no effect on the breakdown of proteoglycan of articular cartilage. Based on these findings, IL-8 released from monocytes and synovial cells may be an important contributor to leukocyte accumulation and inflammatory events in the joints of RA. PMID- 1932368 TI - The release of interleukin-1 beta (IL-1) precedes that of interleukin 6 (IL-6) in patients undergoing major surgery. AB - The cytokine response to major surgical trauma has been studied in six patients undergoing elective aortic surgery. Peripheral blood was sampled frequently before, during, and after surgery and the plasma cytokines interleukin-1, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma were measured using enzyme-linked immunosorbent assays. These results were reviewed together with the operative details, clinical course, and C-reactive protein levels. Tumor necrosis factor-alpha and interferon-gamma were not detected in these patients. An early and short-lived interleukin-1 beta response to major surgery was detected only by intensively sampling the intraoperative period. This was a consistent finding that preceded the rise in interleukin-6. Interleukin-6 rose steeply from 2 h, peaking between 4 and 24 h. It had fallen sharply by 48-72 h in five patients who had an uneventful postoperative course. It remained high in one patient who developed complications and fell only when a severe septicemia was treated successfully. His interleukin-6 levels were considerably higher than the other patients even during the operation itself. There was no obvious relation between the interleukin-6 peak and the duration of operation. A sequential interleukin-1 beta and interleukin-6 response has not been noted before in vivo, and would seem to provide evidence supporting the in vitro observation that interleukin-1 induces interleukin-6 synthesis and release. It also provides evidence of an important role for interleukin-6 in the body's response to injury. A larger study is in progress. PMID- 1932369 TI - Human recombinant granulocyte-macrophage colony-stimulating factor augments viability and cytotoxic activities of human monocyte-derived macrophages in long term cultures. AB - In the present study we investigated the effect of human recombinant granulocyte macrophage CSF (GM-CSF) on the in vitro maturation of human monocytes into macrophages, and followed the biochemical and functional changes in the cells during this process. Adherent human peripheral blood monocytes cultured for up to 3 weeks in the presence of GM-CSF were examined for viability and adherence, beta glucosaminidase activity, oxidative burst activity, expression of fucosyl mannosyl receptors, and TNF-alpha production. The cultured monocytes increased in size and protein content and matured into macrophages within 12 to 18 days. GM CSF treatment increased by 2.5-fold the number of adherent cells after 2 weeks in culture, but did not change the beta-glucosaminidase and oxidative burst activities of the cells compared to nontreated controls. GM-CSF increased the capacity of monocyte-derived macrophages to bind yeasts and bacteria via fucosyl mannosyl receptors, by both augmenting the viability of the adherent cell population and by elevating the expression of such receptors per cell. GM-CSF treated macrophage cultures also showed elevated production of TNF-alpha. The results described here showed that GM-CSF facilitated the long-term maturation of monocytes into macrophages, augmented their capacity to capture bacterial and fungal cells, and elevated the release of cytokines involved in inflammatory and granulomatous reactions. PMID- 1932370 TI - Influence of endogenous glucocorticoid on endotoxin-induced production of circulating TNF-alpha. AB - Mice are quite resistant to LPS toxicity but even a small dose induced a monophasic production of circulating TNF. In BCG-treated mice challenged with LPS, the greater susceptibility was associated with the capacity of producing elevated levels of TNF in the blood. During pregnancy, after adrenalectomy, and particularly after treatment with galactosamine, smaller amounts of LPS were lethal in mice. Using adrenalectomized mice, which are less sensitive to LPS toxicity than galactosamine-treated mice, it was shown that smaller doses of LPS were effective in inducing TNF release in comparison with intact animals, and that larger concentrations of serum TNF were obtained. Pretreatment of adrenalectomized mice with MDP before LPS elicited a priming effect for an enhanced TNF production that reached levels comparable to that found in BCG primed mice. Whatever was the yield of circulating TNF, the pattern of response was similar peaking at 1.5 to 2 h to LPS injection and returning to baseline values within 4 h. Prior administration of glucocorticoid was effective in preventing the release of serum TNF in adrenalectomized mice. The level and the kinetics of serum TNF following LPS injection were not modified in pregnant or in galactosamine-treated mice, and as in control animals glucocorticoid administration prior to LPS inhibited the TNF response. PMID- 1932371 TI - Macrophage migration inhibitory factor (MIF) produced by a human T cell hybridoma clone. AB - A macrophage migration inhibitory factor (MIF) was purified to homogeneity from the serum-free culture supernatant of a human T cell hybridoma clone called F5. This clone was established by means of somatic fusion, using the emetine actinomycin D selection method, and produced a large amount of MIF. The MIF activity in the culture supernatant of F5 cells was not due to contaminating interferon-gamma (IFN-gamma), which is known to possess MIF activity. Furthermore, other known cytokines, such as tumor necrosis factor (TNF), interleukin-1 (IL-1), and granulocyte-macrophage colony-stimulating factor (GM CSF), were also revealed to have MIF activity, but our MIF was different from these known factors. F5 cells produced two species of MIF that could be separated on a phenyl-Sepharose column. MIF-1 (the more hydrophilic species of the two) was purified to homogeneity by sequential hydrophobic chromatography, ion-exchange chromatography, dye ligand affinity chromatography, and high-performance liquid chromatography (HPLC) on ion-exchange and reverse-phase columns. Finally, 4600 fold enrichment, as to specific activity, of MIF-1 was achieved. The purified MIF 1 was digested with endoproteinase Lys-C into some peptide fragments and the amino acid sequences of the peptides obtained were determined. No sequence identity between our MIF-1 and other proteins was observed. Then, antibodies were raised against a peptide synthesized according to the determined amino acid sequence. They specifically reacted with MIF-1 and reduced its migration inhibitory activity. Based on these results, we conclude that the determined amino acid sequence was certainly that of MIF-1. PMID- 1932373 TI - Bradykinin induces interleukin-6 and synergizes with interleukin-1. AB - Bradykinin was found to induce production of IL-6 in human diploid fibroblasts, as well as in a hepatoma-derived cell line, but not in a human melanoma or an osteosarcoma cell line. With the exception of the melanoma cell line, these cells were also found to be responsive to IL-1 beta. The response to bradykinin was faster but less high than that induced by IL-1. Experiments in which IL-1 (-alpha or -beta) and bradykinin were applied simultaneously revealed a synergistic interaction. Of the other cytokines tested, TNF-alpha and IFN-gamma weakly induced IL-6. Neither IL-2, IFN-alpha, nor IFN-beta was able to induce IL-6, either in the absence or the presence of bradykinin. These observations constitute further evidence for the existence of interactions between cytokine and noncytokine peptides, thus linking the neuroendocrine and immune systems. PMID- 1932372 TI - Antitumor activity of TNF-alpha, IL-1, and IFN-gamma against three human osteosarcoma cell lines. AB - Osteosarcoma is the most common primary malignant bone tumor. The peak incidence is in adolescence and the prognosis is very poor. Even after amputation and chemotherapy, many patients who suffer from osteosarcoma die of lung metastases within 2 years. This report documents a study of the in vitro antitumor activity of cytokines against three human osteosarcoma cell lines. The cell lines MG-63, SAOS-2, and TE-85 were incubated with TNF-alpha, IL-1, or IFN-gamma alone or in combination. TNF-alpha, IL-1, and IFN-gamma had antiproliferative activity against all three cell lines. TNF-alpha and IFN-gamma were the most effective against SAOS-2; MG-63 cells were the most sensitive to IL-1, and TE-85 cells were resistant to TNF-alpha and IL-1 but sensitive to IFN-gamma. The synergistic antitumor effect of TNF-alpha plus IFN-gamma, IL-1 alpha, or IL-1 beta or of IFN gamma plus IL-1 alpha or IL-1 beta was higher than that obtained when the cytokines were employed alone. PMID- 1932374 TI - Plasma disappearance and organ distribution of recombinant human tumor necrosis factor-alpha in rats. AB - The potential use of TNF as a therapeutic agent requires knowledge of the rate and mechanisms of its plasma and tissue clearance and its cellular localization. We have explored these issues using a male Sprague-Dawley rat model and a specific radioimmunoassay for human TNF that does not cross-react with rodent TNF. Unlabeled and 125I-labeled TNF were administered by intracardiac injection. A biexponential clearance was observed with t1/2 (beta-phase, metabolic) of 280 min for TCA-precipitable 125I-labeled TNF and t1/2 (beta-phase) of 30 min for unlabeled TNF. The Sephadex G-75 profile for 125I-labeled TNF obtained 2 min and 4 h after intracardiac injection did not differ significantly except for an increase in the amount of free 125I at 4 h compared to 2 min. Scatchard plot analysis suggests that 125I labeling alters significantly the binding of TNF to its receptors on FRTL-5 cells. 125I-labeled TNF uptake by 18 different tissues was corrected for the 125-labeled TNF in the vascular space by simultaneous injection with 131I- or 99mTc-labeled albumin. The 125I-labeled TNF tissue/plasma ratio was greater than 1.0 in adrenal, pituitary, lung, spleen, liver, and kidney. Most of these tissues have previously been shown to have TNF receptors and to experience the greatest endothelial damage in response to TNF administration. PMID- 1932375 TI - Lymphocytes infiltrating ovarian malignant ascites: modulation of IL-2-induced proliferation by IL-4 and of selective increase in CD8+ T cells by TNF-alpha. AB - Lymphocytes infiltrating ovarian malignant ascites (TALs) were propagated in vitro in the presence of low (20-50 U/ml) concentrations of recombinant interleukin-2 (rIL-2) and moderate concentrations of interleukin-4 (IL-4) and tumor necrosis factor type alpha (TNF-alpha). Neither IL-4 nor TNF-alpha alone induced proliferation of ovarian TALs, but IL-4 and TNF-alpha synergized with IL 2 in enhancing the proliferation of T cells from cultures and inducing a more specific pattern of cytotoxic responses of ovarian TAL. IL-4 enhanced the proliferation of TAL cultures in the induction phase, but did not synergize with IL-2 in enhancing the proliferation and cytotoxicity of an established autologous tumor-specific CD8+/CD4- cytotoxic T lymphocyte (CTL) line. In contrast, TNF alpha-induced preferential expansion of CD8+ CTL in TAL cultures where CD3+/CD4+ cells were initially in excess and of an established autologous tumor-specific CD8+ CTL line. This expansion resulted in increased levels of cytoxicity against autologous tumor cells. Amplification of IL-2 growth-promoting effects and selective enrichment in T cell subsets by IL-4 and TNF-alpha may therefore be useful in cellular adoptive immunotherapy using tumor-specific T cells. PMID- 1932376 TI - Cytokine-mediated regulation of human leukocyte gelatinases and role in arthritis. AB - Gelatinases (type IV collagenases) produced by normal peripheral blood leukocytes were studied by the use of a substrate conversion assay. When monocytes were stimulated with IL-1 beta discrete amounts of a 85-kDa gelatinase were detected. This type of gelatinase comigrated with a phorbol ester-inducible metalloproteinase from human tumor cells. The levels of induction of the monocytic enzyme after stimulation with IL-1, double-stranded RNA, LPS, and mitogens paralleled those of the secondary cytokine IL-6. When peripheral blood neutrophils were stimulated with IL-8 or PMA significant amounts of a 91-kDa neutrophil gelatinase were released, whereas with IL-1 beta no effect was observed. Both neutrophil and monocyte gelatinases cross-reacted in immunoprecipitation experiments with tumor cell-derived gelatinases. Further evidence for structural similarity between the IL-1-inducible monocytic (85 kDa) and the IL-8-regulated neutrophilic (91 kDa) gelatinases was obtained after purification of the proteins to homogeneity: both gelatinases possessed an identical amino terminal amino acid sequence and appeared as truncated forms of gelatinase from tumor cells. Synovial fluids of arthritic joints contained extremely high concentrations of the 91-kDa gelatinase. The concentrations of this type of gelatinase were correlated with the titers of the marker cytokine IL 6. The controlled production and activity of leukocyte-derived gelatinase may play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. In the arthritis patient this enzyme might contribute to the pathogenesis of joint destruction and might constitute a useful marker of disease status. PMID- 1932377 TI - Interleukin-1 and tumor necrosis factor-alpha in plasma of patients with acute ischemic heart disease who undergo thrombolytic therapy: a randomized, placebo controlled study. AB - In patients with acute ischemic heart disease who undergo thrombolytic therapy we have previously observed a marked endothelium-dependent activation of the coagulation system. Concomitantly the concentrations of the fast acting plasminogen activator inhibitor type 1 (PAI-1) in plasma increased. The results of recent in vitro studies would suggest that these in vivo phenomena could be associated with the procoagulant effects of the cytokines interleukin-1 (IL-1) and/or tumor necrosis factor-alpha (TNF). In the present placebo-controlled study on patients with acute ischemic heart disease treated with thrombolytic agents we observe low or undetectable concentrations, and insignificant deviations during the study periods, of IL-1 and TNF in plasma. We conclude that IL-1 and TNF play a minor role for generation of coagulant activity and systemic deviations of PAI 1 in patients who undergo coronary thrombolysis. PMID- 1932379 TI - Communicating successfully with attorneys. PMID- 1932378 TI - Purification and characterization of natural human interleukin-3. AB - The human interleukin-3 gene was cloned in 1986 and the biochemical and biological properties of recombinant human interleukin-3 (rhuIL-3) protein were described. In this report we compare rhuIL-3 with nonrecombinant, natural huIL-3, purified from the supernatant of the human T cell leukemia line Jurkat. The main purification step, affinity chromatography, using a selected monoclonal anti-huIL 3 antibody, resulted in an approximately 40,000-fold enrichment of huIL-3. Combination of this step with ion-exchange and reverse-phase chromatography yielded natural huIL-3 of high purity (greater than 98%). A highly sensitive and specific sandwich ELISA, comprising two epitope-mapped monoclonal anti-huIL-3 antibodies, was used to quantitate huIL-3 during purification. Amino acid sequence determination revealed that the 38 N-terminal amino acids of Jurkat derived huIL-3 are identical to the published sequence deduced from human fetal liver genomic DNA but differ in one residue from that derived from human T cell clones. The degree of glycosylation of Jurkat-derived huIL-3 was similar to Chinese hamster ovary cell-expressed rhuIL-3. Natural huIL-3 showed very similar biological activities to rhuIL-3 in proliferation and receptor binding assays utilizing huIL-3 responsive primary cells and cell lines, as well as in the human bone marrow colony assay. PMID- 1932380 TI - Cultivating good client relationships. PMID- 1932381 TI - The legal nurse consultant's role in product liability cases. PMID- 1932382 TI - Experiencing a trial. PMID- 1932383 TI - What lawyers look for in their consultants and experts. PMID- 1932384 TI - Plasma methionine enkephalin levels in the human newborn at birth. AB - Plasma met-enkephalin immunoreactivity (MET-ENKi) and catecholamine levels were measured in umbilibal cord blood from 46 healthy newborn infants. Clinical data including Apgar scores, birth weight, gestational age, route of delivery, fetal heart tracings and arterial blood gas values were also obtained. Thirty-nine infants were delivered by the vaginal route. All but 1 infant delivered by cesarian section had undergone a trial of labor. Plasma MET-ENKi in the newborn infants was markedly greater than levels found in healthy adult volunteers: 360 +/- 25 versus 25 +/- 2 pg/ml, respectively. MET-ENKi levels were similar in umbilical arterial and umbilical venous blood, and in infants delivered vaginally or by cesarian section. PMID- 1932386 TI - Serum alpha 2-HS-glycoprotein levels in neonatal infections. AB - The serum concentration of alpha 2-HS-glycoprotein was determined in 15-infected neonates and 21 age-matched controls using the radial immunodiffusion method. The infected neonates had significantly lower serum alpha 2-HS-glycoprotein concentration than the controls (56.9 +/- 15.1 and 105.6 +/- 25.7, respectively; p less than 0.001) confirming that it also behaves as a negative acute phase reactant in neonates. No correlation was found between alpha 2-HS-glycoprotein and albumin concentrations. The serum glycoprotein concentration in the control neonates was significantly higher than that of healthy older children and reported values in adult controls. The often reported decrease in the opsonic function of the neonatal serum is therefore unlikely to be explained by decreased alpha 2-HS-glycoprotein levels. However, the relatively higher levels of the glycoprotein observed in this study in neonates may be related to the active bone mineralization taking place in the newborn period. PMID- 1932385 TI - Postnatal changes in proximal and distal tubular sodium reabsorption in healthy very-low-birth-weight infants. AB - We studied 7 healthy very-low-birth-weight male infants with a mean birth weight of 1,195 g and a gestational age of 29.0 weeks, from birth to 6 weeks. The filtered Na load increased fivefold but urine Na excretion decreased from 3.4 to 0.1% of the filtered Na load. The efficiency of Na reabsorption increased 8% in the proximal tubule compared with 66% in the distal tubule. Because greater than 90% of Na reabsorption always occurred proximally, the smaller percentage increase in efficiency of the proximal tubule contributed as much as the larger percentage increase in efficiency of the distal tubule to the postnatal improvement in renal Na conservation. PMID- 1932387 TI - Interaction between caffeine and zinc on brain in newborn rats. AB - The purpose of this study was to determine whether adding zinc to the caffeine supplemented diet of dams during gestation and lactation would affect brain development in newborn rats. On day 9 of gestation, dams of group 1 were fed to a 20% protein diet as a control. Dams of group 2 were fed a 20% protein diet supplemented with caffeine. Dams of group 3 were fed a 20% protein diet supplemented with caffeine and zinc. The amount of caffeine added to the maternal diet was 2 mg/100 g of body weight. The amount of zinc chloride added to diet was 0.6 g/kg of diet. At birth, 8 randomly selected pups from each group were assigned to each dam of the respective group and were continuously fed the same diet. On day 15, the pups were killed and brains were removed. Zinc, protein, DNA, alkaline phosphatase activity and cholesterol contents were measured. Milk and maternal and neonatal blood were collected to determine caffeine levels. There was a significant correlation between the milk caffeine and brain caffeine concentrations in group 3. A significant correlation between the neonatal plasma caffeine and brain caffeine concentrations was observed in groups 2 and 3. There was no correlation between neonatal brain weight and zinc content per brain in each group. The correlation between neonatal brain weight and alkaline phosphatase activity was significant in groups 1 and 3. The neonatal zinc content and concentration of group 2 was less than that of group 1. The DNA content and concentration of group 3 was greater than that of either groups 1 or 2. Supplementation of zinc to the caffeine-added diet could restore the brain zinc levels observed in brains of newborn rats. PMID- 1932388 TI - Spectral edge frequency of the EEG in healthy neonates and variation with behavioural state. AB - Spectral edge frequency (SEF) of the EEG was studied in 51 healthy neonates to assess its value as a measure of cerebral maturation. SEF was calculated as the frequency below which 95% of the power in the power spectrum resides. Summated SEF (sSEF) of 4 EEG channels correlated significantly with gestational age (r = 0.83). sSEF varied with behavioural state and with EEG derivation. Intra- and interindividual variability were both greater in preterm compared to term babies. We conclude that SEF is a useful measure of cerebral maturation in the newborn and may have a role in studying stressed newborns. PMID- 1932389 TI - Comparison of short term indirect calorimetry and doubly labeled water method for the assessment of energy expenditure in preterm infants. AB - The accuracy of 8-hour indirect calorimetry (IDC) as an estimate of energy expenditure was investigated in 8 healthy preterm infants (birth weight 1,270 +/- 193 g, gestational age 32 +/- 3 weeks, mean +/- SD) in comparison with an analysis over 5 days using the doubly-labeled water (2H2(18)O) method (DLW). The infants that were fed continuously by nasogastric drip with 120 kcal/kg/day of special infant formula were measured twice under thermoneutral conditions in a closed system indirect calorimeter during 8 h with a 4-day interval; simultaneously isotope decay was measured by isotope ratio mass spectrometry in urine samples collected daily during 5 days from 6 h after an oral dose of 2H2(18)O on the first day of IDC, all during the 4th postnatal week. The mean differences between carbon dioxide production rate (rCO2) measured either by single 8-hour IDC or by duplicate 8-hour IDC and the 5-day DLW method, using the two-point analysis or the multipoint analysis were not significantly different from zero. The rCO2 calculated from the DLW method using the two-point analysis differed -1.4 +/- 1.7% from that measured by the multipoint analysis. The mean differences between the metabolic rate estimated from 8 h of IDC and from the 5 day DLW method based on a measured RQ of 0.90 was -6.7 +/- 6.2% and based on the RQ of the feeding -4.5 +/- 6.0%. These differences were not significantly different from zero. We conclude that IDC over 8 h and two-point DLW measurement over 5 days, both methods that can be applied with relative ease in practice, offer an adequate average estimate of energy expenditure in continuously fed preterm infants under thermoneutral conditions. PMID- 1932390 TI - Plasma and erythrocyte amino acids in mother and fetus. AB - Plasma (P) and whole blood (WB) amino acid concentrations were measured in arterial and venous blood of 9 mothers and their fetuses at elective cesarean section and compared to values obtained in 5 normal nonpregnant women. Erythrocyte (E) amino acid concentrations were calculated from P and WB concentrations. E/P ratios were significantly greater than 1.0 in all groups studied. Alanine, glycine, and serine presented E/P ratios significantly higher in pregnant women than in control nonpregnant women. Fetuses presented significantly lower E/P ratios for lysine than pregnant and nonpregnant women. Uterine arteriovenous amino acid differences were not significantly different from zero in both plasma and erythrocytes. Umbilical venous-arterial differences were significantly positive for most essential amino acids in plasma, whereas they were not significantly different from zero in erythrocytes. This finding suggests that erythrocytes do not play a major role in the transfer of amino acids from the placenta to the fetus. PMID- 1932391 TI - Changes in auditory brainstem responses of normal neonates immediately after birth. AB - To clarify the functional changes in the acoustic conduction pathway in the human immediately after birth, auditory brainstem responses (ABR) in 58 normal neonates were examined. In longitudinal and cross-sectional analysis, the peak latency of wave 1 showed significant shortening (p less than 0.05) from 1.82 +/- 0.23 ms (mean +/- SD) at 30 min after birth to 1.69 +/- 0.26 ms at 2 h after birth. It continued to decrease gradually therafter. The interpeak latency of waves 1-3 decreased gradually (not significant) from 2.82 +/- 0.19 ms (30 min after birth) to 2.74 +/- 0.15 ms (1 month after birth), while the interpeak latency of waves 3 5 decreased significantly from 2.63 +/- 0.27 ms (30 min after birth) to 2.47 +/- 0.23 ms (24 h after birth; p less than 0.01). These results indicate that functional changes in the acoustic system immediately after birth represent rapid adaptation of the peripheral region to extrauterine environment and development of the more central region. PMID- 1932392 TI - Putting the "public" back in mental health, the "mental" back in public health. PMID- 1932393 TI - Midlatency auditory evoked responses in schizophrenia. AB - The auditory evoked component P50 has been reported as having an abnormal recovery cycle in patients with schizophrenia. Recent studies examining the effects of stimulus rate on the midlatency response (MLR) component P1, found P1 recovery cycles in normals similar to P50. This study examined the P1 recovery cycle in patients using a rate protocol and MLR recording procedures. MLRs were recorded from 13 controls and 13 patients with schizophrenia in response to binaurally presented clicks presented at three stimulus rates: 0.9/sec, 5.1/sec, and 9.9/sec. The P1 (50-70 msec latency) in patients did not decrease as much in amplitude as in controls at the 9.9/sec stimulus rate. This lack of recovery was correlated with clinical ratings of symptomatology. Since evidence from both the human and the cat model suggests that the P1 is generated in thalamus, these findings are consistent with reports of thalamic dysfunction in schizophrenia. PMID- 1932394 TI - Ventricular enlargement and caudate hyperdensity in elderly depressives. AB - Twenty-five elderly patients (mean age 73 years, range 61-88 years) with major depression underwent cranial computed tomography (CT). The findings were compared with healthy age- and sex-matched controls. The radiodensity of the left and right heads of the caudate was significantly higher in the depressed patients (p less than 0.05). The third ventricle was significantly enlarged (p less than 0.05); this effect did not reach statistical significance for the lateral ventricles. Ventricle size in the patient sample increased with age, duration of illness, and number of depressive episodes. This effect was largely age-driven for the third ventricle. Enlargement of the anterior horns appeared to be primarily influenced by the combined effects of early onset and bipolarity of illness. Densitometric measurements of the grey and white matter did not show significant correlations with age, number, or frequency of depressive episodes, age of onset, or duration of illness. PMID- 1932395 TI - Plasma free homovanillic acid (HVA) as a predictor of clinical response in acute psychosis. AB - The relationship of plasma free homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) to early clinical response was prospectively studied in a new series of acutely psychotic inpatients given a fixed dose of perphenazine elixir for 10 days. Elevated pretreatment plasma HVA but not MHPG was significantly associated with good response. Change in HVA was correlated with a favorable response and a significant decline in MHPG was found in responders. Results suggest that HVA can provide a useful clinical predictor of response, and that both dopamine metabolism and noradrenergic functioning, as measured by plasma HVA and MHPG, are reduced in effective neuroleptic treatment. PMID- 1932396 TI - Enhanced retrieval of unpleasant memory in helpless rats. AB - Several studies in humans have indicated an association between enhanced retrieval of unpleasant events and depressive mood. No analogy has so far been demonstrated in animals, however. The purpose of the present study was to determine the effect of learned helplessness on the retrieval of unpleasant memory in rats. Animals initially exposed to a single unpleasant event in a passive avoidance task were subjected, respectively, to inescapable, escapable, or no shock stress exposure. A retention test conducted 48 hr following stress exposure showed an enhanced performance for the passive avoidance task in rats subjected to inescapable shock stress. This improved performance was not observed in escapable or no shock stress groups. This finding in the learned helplessness condition in rats, is qualitatively similar to that found in humans in depressive mood. PMID- 1932397 TI - Blood glucose and insulin response in patients with senile dementia of the Alzheimer's type. PMID- 1932398 TI - Lithium lengthens circadian period but fails to counteract behavioral helplessness in rats. PMID- 1932399 TI - DSM-III-R state anxiety symptoms in anxiety disorder patients. PMID- 1932400 TI - Treatment of chronic schizophrenia with cyproheptadine: a double-blind placebo controlled study. PMID- 1932401 TI - Pericallosal arterial ectasia and manic-depressive illness. PMID- 1932402 TI - Lorazepam, amitriptyline, and sulpiride: withdrawal effects. PMID- 1932403 TI - Alfred Hoche and the elimination of the unit. PMID- 1932404 TI - Propanolol for fluoxetine-induced akathisia. PMID- 1932405 TI - A model of smooth pursuit performance illustrates the relationship between gain, catch-up saccade rate, and catch-up saccade amplitude in normal controls and patients with schizophrenia. AB - Smooth pursuit eye-tracking performance of 37 unmedicated patients with schizophrenia and 45 normal controls was recorded with infrared oculography, and digitized for off-line analysis of gain and other measures. Target velocity was 5 degrees/sec. Patients with schizophrenia had significantly lower gain than normal controls, confirming several earlier reports. During low gain smooth pursuit tracking, when eye velocity is slower than target velocity, the saccadic system corrects for the accumulating position error with catch-up saccades (CUS). The rate of CUS and the median CUS amplitude were compared between groups. Patients had significantly more CUS than controls, but the median CUS amplitudes were not significantly different. A nonlinear mathematical model of the relationship between gain, CUS amplitude, and CUS rate during steady-state constant velocity tracking was developed to integrate these findings. According to this model, for a given gain, correction for position error can result from either a few large CUS or many small CUS. The fit of the model to empirical data, as assessed graphically and with linear and nonlinear regression techniques, was excellent. The model fit the data for both patients and controls. The psychiatric eye tracking literature is discussed from the perspective suggested by the modeled relationship. PMID- 1932406 TI - The TRH stimulation test in Alzheimer's disease and major depression: relationship to clinical and CSF measures. AB - A blunted thyroid-stimulating hormone (TSH) response to exogenous thyrotropin releasing hormone (TRH) has been reported to occur consistently in patients with major depression and less consistently in patients with Alzheimer's disease (AD). In this study we compared the TSH response to TRH in a large group (n = 40) of AD patients, elderly patients with major depression (n = 17), and age-matched controls (n = 14) to further characterize how it may relate to clinical variables, baseline thyroid function tests, and cerebrospinal fluid measures. Comparisons of TRH stimulation test response across all three groups revealed that patients with major depression had lower stimulated TSH levels (delta maxTSH) (p less than 0.02) and higher (though still within normal limits) mean thyroxine (T4) levels (p less than 0.05) than the AD patients or controls. AD patients with a blunted TSH response had a significantly higher mean free T4 (FT4) level (p less than 0.03) and tended to be more severely demented (p less than 0.01) than those with a nonblunted response. PMID- 1932407 TI - Longitudinal effect of amitriptyline and fluoxetine treatment on plasma phenylacetic acid concentrations in depression. AB - Unconjugated (U-PAA), conjugated (C-PAA), and total phenylacetic acid (T-PAA) concentrations in blood plasma and monoamine oxidase (MAO) activity in platelets towards phenylethylamine (PE) were determined in 40 drug-free, depressed patients (23 melancholic, 17 nonmelancholic) from five psychiatric treatment centers, and in 34 normal healthy volunteers. No significant differences were found between controls and all depressed patients or between melancholic and nonmelancholic depressed patients. Treatment of the depressed patients with amitriptyline or fluoxetine over a 6-week period resulted in clinical improvement and in a significant increase in plasma PAA concentrations. A decline in the Beck and Hamilton rating scores during treatment correlated significantly with increases in the concentrations of unconjugated, conjugated, and total phenylacetic acid but not with MAO activity, which did not change during treatment. At each of the three assessment times, however, plasma PAA concentrations and psychiatric rating scores were not significantly correlated. Except for higher end-of-study T-PAA concentrations in the amitriptyline-treated subjects, no significant differences were found between the effects of the two drugs with regard to plasma phenylacetic acid levels, MAO activity, or rating scores. PMID- 1932408 TI - Increased serotonin platelet uptake after tianeptine administration in depressed patients. AB - Tianeptine is a new antidepressant drug reported to enhance serotonin (5 hydroxytryptamine [5-HT]) uptake in rat brain. The effect of tianeptine on 5-HT platelet uptake was studied in 10 depressed patients treated for 28 days. Tianeptine increases Vmax of 5-HT platelet uptake during treatment without inducing any change in Km. As early as 2 hr after the first administration, Vmax increased significantly (+23%, alpha = 0.01). Although of a lesser magnitude, 5 HT platelet uptake remains increased after chronic administration (+14% on day 10 and +13% on day 28). This suggests that tianeptine affects 5-HT platelet uptake sites, either directly or via an action on modulators of 5-HT uptake. These results, in contrast with the action of other tricyclic antidepressants, confirm the original action of tianeptine on 5-HT platelet metabolism. PMID- 1932409 TI - Elevated awakening thresholds in sleep stage 3-4 in war-related post-traumatic stress disorder. AB - Awakening thresholds from sleep stage 3/4 were investigated in 19 DSM-III defined, war-related post-traumatic stress disorder (PTSD) patients compared with 6 normal controls. Patients had significantly higher awakening thresholds and significantly longer latencies to an arousal response than controls. These results are interpreted to suggest modifications in the depth of sleep as one of the long-term sequelae of traumatic events. PMID- 1932410 TI - Antidepressant and memory effects of combined thyroid hormone treatment and electroconvulsive therapy: preliminary findings. PMID- 1932411 TI - Hypertonic saline infusion induces panic in patients with panic disorder. PMID- 1932413 TI - [Poverty, mental health and survival strategies]. AB - The relation between "poverty and mental health" has long been established. However, the dynamic underlying the relation between social and psychic processes has received much less attention. This article presents certain preliminary results of research whose aim is to promote the emergence of the multiple dimensions behind the problematic of mental health in social conditions characterized by extreme poverty. In addition, the authors base their approach on the assumption that human beings, even underprivileged, are very active players, and explore the strategies that are hereby developed in order to maintain or recover their equilibrium. PMID- 1932412 TI - Lithium and calcium channel blockers: possible neurotoxicity. PMID- 1932414 TI - [Post natal depression: the socio-environmental factors]. AB - In the weeks and months that follow the birth of a child, between 10 and 20 per cent of mothers experience serious or moderate symptoms of depression. This state of psychological distress affects the mother-infant interaction, and can modify the child's development in the longer term. Recent studies increasingly link these symptoms to environmental and psychosocial stress factors. The setting up of relevant and efficient prevention and promotion programs requires a better understanding of the effect of stress and social support on the mental health of mothers. PMID- 1932415 TI - [Parent-child relations within the context of immigration. What we know and we should know]. AB - This article presents an overview of the actual and potential state of knowledge on parent-child relationships within the context of immigration. In addition, it examines the impact of parent-child relationships on the development of the child. The first part gives an update on empirical research carried out in that and an analysis of criticism by specialists in the field. The second half, which focuses on studies originating from disciplines other than child psychology, suggests approaches other than the simple intercultural comparison and underscores the true issue of immigration on family relationships, the complexity of the parental task with regard to immigration, its dynamic properties as well as the adaptation that is required. The author goes on to describe more specifically the role of the cultural and ecological contexts, the double cultural influence to which parents are exposed, the difficulties in relation with the transition and the attitudes of parents during the culture-learning process. PMID- 1932416 TI - [The challenges of psychology facing contemporary conjugal phenomena]. PMID- 1932417 TI - [Maturescence, a critical phase between ages 40 and 65. Health, illness, aging and social ages]. AB - The recent emergence of a critical phase in life called maturescence, situated between the ages of 40 and 65, is a by-product of social life in industrialized societies. Because it is considered as a crossroads, this phase in life is not connected with any particular chronological age, such as reaching forty or fifty. Rather, it involves the difficulties of aging in society and the oncoming of identity conflicts, all of which must be seen in relation with the specific health-related problems that result from aging. PMID- 1932418 TI - [The role of conjugal relations in the abuse and neglect of children: towards an ecological study]. AB - The phenomenon of child abuse and neglect has always existed in Western society. Yet, it is only recently that clinicians and researchers have taken a serious look at these problems. This ever growing interest has come about from not only the stunning number of cases identified each year, but also by the extent and gravity of consequences observed among children. Several professionals interested by the issue have put forward a great number of etiological factors to try to explain abuse and neglect within the family unit. However, when assessing the proposed theoretical models (psychiatric/psychological, sociological, systemic), it appears that certain simple factors can play a large role, for instance the history behind parental development, the quality of marital relations, the child parent relation, the stress and the extent of the social network, but none of these can clearly differentiate abusive families from non abusive families. It seems however that these different explicative factors would be even more valuable if they were considered in interaction rather than taken individually. Inspired by the ecological framework proposed by Bronfenbrenner (1977, 1979), Belsky (1980, 1984) as well as Cicchetti and Rizley (1981) have also developed a model that simultaneously takes into account all of these factors and their interaction. PMID- 1932419 TI - [The newborn and the couple: adversaries or partners?]. AB - We generally accept that the planned arrival of a first child is a source of joy for the new parents and that it provides them with a sense of accomplishment. Traditionally, society welcomes the formation of a family unit and looks forward to this passage into the new role of parenthood. However, not only has research on marital relations set aside the popular imagery of romanticism, but it has increasingly given negative connotations to this crisis-prone transition phase. The objective of this article is therefore to review literature concerning the impact of a newborn child on the marital experience, and to nuance the idea that childbirth can lead to crisis situations within the couple. In conclusion, the authors argue that the concept of marital satisfaction needs to be reformulated. Judging from their brief overview of literature, the authors believe the concept to be too narrowly defined and slightly ambiguous. Indeed, researchers have not yet reached a consensus on the definition of marital satisfaction. Furthermore, they tend to operationalize the concept in very different ways. As a result, there is a lot of conclusion and the fact that many researchers use different terms as a synonym of satisfaction is no help. What's more, the assessment of quality in a relationship should not be limited to measuring the level of satisfaction of the two partners. Other dimensions (e.g. adjustment, commitment, cohesion, etc.) deserve consideration in order to give a more complete image of the changes that occur over the years within the couple. PMID- 1932420 TI - [The influence of conjugal conflict on the child: review of research, theory and practice]. AB - The demographical phenomena that have affected families for three decades is raising new interest in the study of how marital relations influence the psychosocial development of the child. Firstly, the authors briefly describe the state of scientific knowledge with respect to the effect of marital conflicts on the psychosocial adaptation of the child. Secondly, the authors make an effort to go beyond the negative effects of marital conflict on children, and discuss the theories and concepts that attempt to explain the covariation, especially concerning specific problems undergone by the child. The third part is devoted to clinical work. It includes an overview of successes and obstacles that still need to be overcome when using preventive measures with children, as well as when supporting the families already experiencing marital conflict. PMID- 1932421 TI - [The marriage therapist is a Trojan horse: reflections inspired by the results of research on interventions with couples]. AB - Communication training and positive exchange training are the two methods for improving marital relations that research has established as being the most effective. However, even after conducting therapy involving both partners based on these methods, too few couples (35%) succeed in reaching the same level of satisfaction as couples who are already satisfied with their relationship. The efforts that have been undertaken to increase this rate have focused mainly on developing new therapeutic techniques that include cognitive, emotional and systemic approaches. However, the results of experimental studies to date do not prove the superiority of these new approaches. Given this situation, it is time to pay more attention to particular characteristics of the therapeutic relation in marital therapy and to the means of obtaining the collaboration of the two spouses. As is the opinion of certain authors, the most difficult clinical task does not consist of finding what the clients must do to solve their problems, but rather to determine how to motivate them and help them achieve their goal. An analysis of this task, based on clinical observations and results of recent research in this area, has allowed the authors to present a number of hypotheses about ways to reinforce the therapeutic alliance and eventually reduce the failure rate of marital therapy. PMID- 1932423 TI - [Mental illness: an illusion?]. PMID- 1932422 TI - [The role of culture in psychiatric epidemiology: an examination of research on Latin American mental health]. AB - In psychiatric epidemiology, culture has often been treated in one of two ways: as a confounding variable to be controlled or as an explanation for unexpected findings. In cases where culture is presented as an explanation, there is often little detailed examination of how culture shapes responses to psychiatric interviews. In this paper, I will argue that culture plays a central role in influencing responses to psychiatric interviews in at least three ways: culture affects the way people respond to psychiatric interviews; culture influences the valuation of specific symptom items; and cultural categories are embedded in responses to psychiatric interviews. Through a review of research on the mental health of Latino populations, I will examine the roles of cultural categories in shaping responses to psychiatric epidemiology studies and will outline an alternative research approach to simultaneously exploring psychiatric diagnostic categories and cultural idioms of distress. PMID- 1932424 TI - [Transparency and ethics in the collection of funds: administrative surveillance or concerted self criticism]. PMID- 1932425 TI - [Types of families, living conditions, functioning of family systems and social maladjustment during latency and adolescence in underprivileged milieus]. AB - Available data on the impact of certain types of families is lacking, and the results are often misleading with respect to maladjustment. Following a description of variations in delinquent activity and behaviour problems according to family type, the authors analyse the difficulties in the operation of family systems. Comparisons of six family types apply to data from 763 boys aged 10, 319 female and 426 male adolescents, aged 14 and 15: intact families, father-based and mother-based single-parent families, father-based and mother-based reconstituted families and substitute families. The article's data show that in the late eighties, nearly 40 per cent of children and adolescents living in low income districts in Montreal belonged to disunited families. In addition, the data confirm a classic observation: in comparison with intact families, disunited families are underprivileged in relation to living conditions, deficient in relation to psychosocial functioning, and propitious to behaviour problems and delinquent activity. In addition, it has been established that certain disunited family types represent a considerable risk factor. The damaging effect of family structure increases in the following order: intact families, mother-based single parent families, mother-based reconstituted families, substitute families, father based reconstituted families and father-based single-parent families. Finally, certain intervention methods are suggested to help prevent behaviour and family problems. PMID- 1932426 TI - [Sex differences in age of onset, symptomatology and evolution of schizophrenia]. AB - Gender differences in age at onset, symptomatology and course of schizophrenia are examined by analyzing case register data and by direct investigation of a representative sample of first-admitted patients. The main finding that males fall ill at an earlier age than females can be confirmed even after ruling out other interpretations due to sample bias, different time span between real onset and first hospital admission, gender differences in symptom development or other confounding factors. When looking for causes of these gender differences it seems that disturbances in early social development must be understood as a consequence of beginning schizophrenia rather than a prerequisite. The need for explanatory models is stressed that allow for the empirical testing of hypotheses concerning gender specific development of schizophrenia. PMID- 1932427 TI - [Insomnia and its treatment in aged persons: a new approach]. AB - Existing hypotheses regarding psychological mediation of disorders in initiating and maintaining sleep only partially explain the phenomenon of insomnia, particularly in aging individuals. In this article we review existing nonpharmacological treatments of insomnia and propose a new way of conceptualizing and treating disorders of initiating and maintaining sleep. The model, based on cognitive and information processing factors, is then used to propose novel approaches to intervention. Because of the prevalence of sleep disruptions in older adults and the limitations of existing pharmacological and psychological treatments with this population, the assumptions of the model and the proposed intervention are explored with particular reference to aging individuals. PMID- 1932428 TI - [The quantitative determination of resistance factors in the saliva of patients with very high caries involvement]. AB - The unstimulated and stimulated whole saliva of patients with a very high caries experience were used for the determination of the flow rate, total protein, and the antibacterial proteins lysozyme, S-IgA and lactoferrin as well as the peroxidase and thiocyanate being components of the salivary peroxidase system. The concentration, the specific concentration and the secretion rate were calculated. PMID- 1932429 TI - [Fluorine distribution in the enamel in the use of glass ionomer cements as bonding materials]. AB - The rise in the fluorine content of dental enamel after bonding orthodontic attachments with glass ionomer cement (GIC) was analysed in an in vitro study. Twenty-four freshly extracted caries-free premolars from adolescent patients were available for investigation. The teeth were cleaved longitudinally in the oro vestibular direction to obtain a test specimen and reference sample. The GIC Aquacem was used as bonding material. The fluorine was measured with an electron beam microprobe (Camebax SX 50) 10, 20, 40 and 80 days after bonding. A rise of fluorine in dental enamel of more than 120% was observed after the bonding procedure. This rise was especially rapid in the first ten days, and a saturation value was reached after 40 days. The depth of penetration into the dental enamel was 20 microns, and the surface spreading was at least 3 mm. An equilibrium state is attained between the 40th and 80th day. A preventive action on caries in the vicinity of attachments bonded with glass ionomer cement is to be expected owing to the accumulation of fluorine in the dental enamel. PMID- 1932430 TI - [The incidence of hypodontia with the presence and absence of wisdom teeth]. AB - Radiographs of 2550 orthodontic patients were evaluated for tooth agenesia dependent on the presence and the missing of third molars. Tooth agenesia (except third molars) was found in 248 patients (9.7%). The missing of third molars occurs at 427 of 2061 patients (20.7%) aged between 12 and 36 years. At 81.5% of all patients with tooth agenesia at least one of the third molars was missing. The rate of agenesia had an amount of 5.9% (97 of 1634 patients) in the group of patients with presence of all third molars. Whereas the rate of agenesia at patients with missing of one or more third molars was with 27.6% especially great. Moreover it was found out, that the rate of agenesia was the greater the more third molars were missing. PMID- 1932431 TI - [The angulation of the base of the skull--a determining factor for facial skeletal development? The significance of the angulation of the base of the skull]. AB - By means of tensor analysis this cephalometric study was undertaken to compare the growth differences of the facial skull of untreated orthodontic patients. We investigated children with small cranial base angle (BaSN = 128-132 degrees) and another group with an angle greater than 132 degrees. In this cross-sectional study we compared the development of the skull from an age of 7 to 8 years to an age of 9 to 10 years. In contrast to patients with small cranial base angle those with flatter base showed an increased vertical growth. The growth of the midface and mandible tend toward a retrognathic face. Angle Cl.-I cases showed a proportional horizontal growth pattern in all regions of the face. PMID- 1932432 TI - [The evaluation of the adhesive properties of dental materials by using radioactive-labelled bacteria]. AB - Dental materials with different surfaces were incubated with 111In-oxine-labelled bacteria Streptococcus mutans 20 min respectively 2 h, 6 h and 24 h. To determine the amount of the bacteria accumulated on the specimens we measured the radioactivity with a scintillation counter. The same measuring was done after decontamination by the help of ultrasonication. The comparison of activities shows that different dental material surfaces adhere different amounts of bacteria. The adhesive properties are material and time dependent, but the surface processing has a lower influence on the bacterial adherence. The lowest degree of bacterial adherence has the cobalt base alloy Gisadent KCM 83. On the other hand the highest remaining activity was found after decontamination of cobalt base alloy and PMMA resin Kallocryl A. PMID- 1932433 TI - [The subciliar incision as an infraorbital approach in caring for midface fractures]. AB - As an infraorbital approach in the operative treatment of fractures of the midface, the zygoma and the orbital floor, the transconjunctival, the subciliar, the median eyelid and the orbital rim incision were proposed. In the Department of Oral- and Maxillofacial Surgery of the University Hospital Kiel we use the subciliar access to the infraorbital region. Between 1983 and 1988 105 subciliar incisions were performed in 448 traumatologic operative procedures. In the clinical follow-up examinations of 52 patients merely three of the cases presented dissatisfying results. We regard this type of incision to represent a favorable approach to the infraorbital region. Disturbing scar formation can principally be avoided. PMID- 1932434 TI - [Wedge-shaped defects of animal teeth]. AB - Wedge-shaped defects of teeth of animals are described. Only herbivorous and omnivorous animals showed them. It is suggested that in addition to a mechanical abrasion there are chemical influences on the organic component of the dentin. PMID- 1932435 TI - [Bilateral gemination of the central incisors in the maxilla]. PMID- 1932436 TI - [The DNA ploidy in squamous cell carcinomas of the mouth floor determined by flow cytometry]. AB - The cellular DNA content of 90 primary squamous cell carcinomas of the floor of mouth was determined by flow cytometry. Aneuploid cell lines were detected in 86% of the cases. The proportion of diploid carcinomas decreased with size (T1: 63%, T2: 11%, T3: 7%) and histologic grade (G1: 17%, G2: 16%, G3: 9%). Only 15% of the diploid, but 61% of the aneuploid tumors showed evidence of lymph node involvement. A 96% sensitivity of the test and a negative predictive value of 85% emphasize the prognostic importance of DNA ploidy in the primary tumor to evaluate the risk of subclinical dissemination. PMID- 1932437 TI - [DNA cytophotometric studies of central giant-cell lesions of the jaw region]. AB - Giant cell nuclear DNA, in 30 giant cell lesions of the jaws, was quantitated by computer-assisted image analysis. DNA content was then used to predict clinical behavior and outcome. Four.nuclei in each of 25 giant cells (total = 100 nuclei) were randomly selected and DNA content was quantitated by the LEITZ Texture Analysis-System-Plus. DNA in nuclei of normal appearing stromal fibroblasts (n = 20) was similarly measured. DNA index was calculated as the mean nuclear DNA content of giant cells divided by mean DNA content of control fibroblasts. The mean DNA index of aggressive lesions (1.09, S. D. = 0.12) was not significantly different from that of non-aggressive lesions (1.18, S. D. = 0.15) (p = 0.093). The results indicate that nuclear DNA content of giant cells is not useful as a predictor of clinical behavior of giant-cell lesions of the jaws. PMID- 1932438 TI - [Qualitative and quantitative studies of the inflammatory reaction in the tumor boundary zone of intraoral squamous cell carcinomas]. AB - The inflammatory cellular infiltration in the tumor boundary zone was analyzed in 10 primary tumors, completely histologically worked up and not pretreated, using a metric and reproducible evaluation system at a line of 10 cm per case. The part of the tumor boundary zone free of inflammation varied between 2% and 79%, where as only 3 of the examined 10 tumor cases showed actions free of inflammation under 10%. In the differential cell picture of the inflammation the lymphocytes dominate (74, 12% +/- 6.79) while the part of plasmacytes varied between 1.8% and 29.2%. In spite of the exclusion of bacterially infected and necrotic tumor sections an average percentage of granulocytes (10.25% +/- 5.30) was ascertained in the inflammatory cell infiltrate. PMID- 1932439 TI - Distribution of traumatic lesions of corpus callosum in "inner cerebral trauma". AB - This study deals with the topographic distribution of traumatic lesions in the corpus callosum within the pattern of "inner cerebral trauma". Material for neuropathological investigations consisted of 49 brains of patients who suffered closed head injury of the acceleration type with linear translation of acceleration acting along the longer axis of the head. As a control, 5 brains were investigated in which the direction of linear translation was latero lateral. The patients were divided into 4 groups according to reconstruction of the traumatic event and ascertaining of the direction of the linear translation of acceleration: (1) Medial blow (antero-posterior and postero-anterior), (2) Semioblique left blow (frontal left-occipital right and occipital right-frontal left), (3) Semioblique right blow (frontal right-occipital left and occipital left-frontal right), (4) Vertex-base direction. Fornix and septum pellucidum, as anatomically adjacent structures were also investigated. The results showed that the lesions in the corpus callosum were related to the pattern of "inner cerebral trauma" (ICT) (Grcevic 1982), and the biomechanical conditions originally proposed by Lindenberg. These investigations, carried out on a representative material of 54 brains and by subserial histological analysis of the entire corpus callosum, produced a new evidence for our previous preliminary observations about the correlation of the shape and distribution of the periaxial lesions of the pattern of "inner cerebral trauma" and direction of the linear translation of accelerating forces. Our present investigations showed a striking congruence between the pattern of lesions within the corpus callosum in such type of cerebral trauma and the course of linear translation of acceleration. Furthermore, this study proved the importance of topographic interpretation of lesions in the corpus callosum in vivo i.e. by the CT and MRI examinations, because they may serve as a significant information for reconstruction of the biomechanical conditions of the injury which can be of importance for early therapeutical strategy and forensic interpretations of the accident. By using silver impregnation-techniques for histopathological study of the corpus callosum, we could confirm our previously expressed concept on "focalized" and not "diffuse" axonal injures in ICT (Grcevic 1988). In this study corpus callosum served as a representative anatomical structure for axonal studies showing that axonal lesions strictly follow the pattern of tissue lesions with definite focal principle. PMID- 1932440 TI - Doppler sonography of the carotid arteries in patients treated by radiation after laryngectomy. AB - The authors examined by Doppler sonography 86 patients undergoing rehabilitation after being treated for malignant tumor of the larynx by radical surgery and radiotherapy. In 39.5% of the patients pathological results were registered mainly in the extracranial segment of the carotids. Focal neurological deficits were registered only in 3 patients, while all the others were asymptomatic. The correlation between the time elapsed after radiotherapy and the stenotic occlusive changes registered in the carotids, as well as the effect of hypertension, diabetes and smoking were analysed. The results suggest the influence of ionizing radiation on the occurrence of stenotic-occlusive processes in the neck segment of the carotid arteries. The population of patients examined is considered at risk of stroke. PMID- 1932441 TI - Stroke epidemiology in Novi Sad. AB - Since the organization of CINDI (Countrywide Integrated Non-Communicable Disease Intervention Programme) and MONICA (Monitoring of Trends and Determinants of Cardiovascular Disease) in 1983 over the whole territory of Novi Sad community it has been found that the incidence of stroke has decreased from 2.68 to 2.36%, the mortality from 67.1 to 42.2% and the number of registered stroke survivors (morbidity prevalence) has increased almost three times. The subjects, material and methods as well as the results obtained so far are presented in this paper. PMID- 1932442 TI - The occurrence of Rosenthal fibres in the brain tissue around meningioma. AB - A case of endotheliomatous type of meningioma arising from the falx and dura of the left anterior cranial fossa is reported. Numerous Rosenthal fibres were observed in the gliotic tissue around the meningioma. Authors present a brief data about the nature and occurrence of Rosenthal fibres. The occurrence of the pilocytic astrocytes and Rosenthal fibres in the gliotic tissue around slow growing falx meningioma is an additional evidence for a peculiar type of changes in astrocytes of the long-standing gliosis of piloid type. PMID- 1932443 TI - Slow measles encephalitis or subacute sclerosing panencephalitis. AB - A 10-year-old boy with subacute sclerosing panencehalitis (SSPE) is presented. The diagnosis was confirmed by typical clinical picture, electroencephalographic changes, post-mortem pathohistological study and high titer of measles antibodies in serum and cerebrospinal fluid. Serum to cerebrospinal fluid ratio of measles antibody titers was 16. The determination of measles antibody titer in the serum and cerebrospinal fluid, by using complement fixation and hemagglutinin inhibition tests, should be done in all patients with SSPE. PMID- 1932444 TI - Dr. Niko Selak (1862-1891)--pioneer of Croatian neurology (on the hundredth anniversary). AB - Dr. Niko Selak (Dubrovnik, 1862--Zagreb, 1891) was a district medical officer in Jastrebarsko, town medical officer and hospital director in Koprivnica, pioneer of Croatian neurology, ophthalmology, medical photography, application of hypnosis in medicine, and the author of the first manual of forensic medicine in Croatia. Among his articles dealing with neurology are those dealing with luetic gumma of the brain, tabes cervicodorsalis, Aran-Duchenne muscular atrophy, bulbar paralysis, etc. PMID- 1932445 TI - [Anesthesia in heart surgery]. PMID- 1932446 TI - [Anesthesia in heart surgery]. AB - Today, the performance of anaesthesia in cardiac surgery is on a high quality level. It requires special knowledge of the various operative techniques, the different methods of extracorporeal circulation and haemodynamic changes of the underlying cardiological disease, as well as extensive experience in cardiac and vasoactive drugs. Heart patients are now being operated on in many departments of cardiac surgery. Over and above this patients with more or less severe cardiac diseases are being looked after in every Department of Anaesthesiology, thus, every anaesthesiologist should acquaint himself with these specific problems during his specialist training. PMID- 1932447 TI - [Risk indicators in coronary surgery]. AB - We examined the perioperative course of 1013 patients who had undergone coronary surgery between 1984 and 1987, to identify preoperative examination findings which are suitable as risk indicators in coronary surgery. The features we paid attention to were: anamnestic data, parameters of coronary disease, haemodynamic parameters and accompanying illnesses. We considered a perioperative course as complicated when systolic blood pressure dropped to 80 mmHg or less for longer than 15 min, when reconnection to the heart-lung-machine was necessary, when an intra-aortal balloon counterpulsation was required, when the patient had to have mechanical ventilation for longer than 24 h, when resuscitation took place, or when the patient died in the hospital. The Chi-square test was used for statistical analysis. Very good risk indicators (p less than 0.001) were: age greater than 60 y, resuscitation history, more than two bypass grafts, SvO2 70%, ejection fraction less than 50% and cardiac index less than 2.5 l/min*m2. Good risk indicators (p less than 0.001) were: functional capacity less than 50 watts, more than one previous myocardial infarction and LVEDP greater than 20 mmHg. LCA stenosis, arterial hypertension with diastolic blood pressure values above 100 mmHg, and obstructive airway disease were identified as suitable risk indicators (p less than 0.05). The following findings were combined with significantly increased mortality: female sex, age over 60 years, two or more previous myocardial infarctions, history of resuscitation, mixed venous oxygen saturation below 70% and the need for three or more bypass grafts for complete revascularisation. PMID- 1932448 TI - [Characteristics of the QT interval in the ECG following reconstructive surgery of the common carotid artery]. AB - In 40 patients undergoing thrombendarterectomy of the common carotid artery, the frequency-corrected QT interval in the ECG, as well as the serum sodium, potassium and total calcium were studied. Examination took place preoperatively 1.-3. hour postoperative and the 1. and 5. day postoperative. In 13 patients, pathological prolongation of QT interval (greater than 440 msec) was already found pre-operatively. Postoperative significant QT interval prolongations could not be found in any patient, independent of the site of operation or pre operative findings. The total serum calcium concentration was postoperatively significantly reduced (P less than 0.01). There was no correlation between the reduced total serum calcium and the QT interval in the ECG. The findings contradict the assumption that clinically relevant reduction of the autonomous cardial innervation is frequent in patients undergoing thromboendarterectomy of the common carotid artery. PMID- 1932449 TI - [Intubation problems of anesthesia in otorhinolaryngology]. AB - Many pathological changes in pharynx and larynx can cause problems in endotracheal intubation. Their preliminary signs and symptoms are often uncharacteristic. Thus prophylaxis is not always possible. Some representative diseases of larynx and pharynx are demonstrated by means of endoscopic photographs and by case reports. The photos were taken during endoscopic examinations in an ENT-clinic. The method of anaesthesia used in these cases is described, as well as prophylactic measures to be taken, if a difficult intubation may be expected. Finally, the procedure in case of an unexpected critical intubation is discussed. PMID- 1932451 TI - [Characteristics of the heart rate of emergency physicians in emergency helicopters]. AB - The heart rate behaviour of 14 emergency doctors was examined in 50 cases of medical emergency service by helicopter. In addition, the subjective stress experienced by the probands was inquired by means of a questionnaire. The alarm and the landing at the site of the emergency resulted in the most marked heart rate increases; also during the period of approaching the patient, his rescue and care, persistent tachycardia could be observed. Recovery began slowly during the return flight, but even 15 minutes after completion of the emergency task the heart rate was still higher than the original value before the alarm had been sounded. Subjectively the total stress was considered to be generally low in the opinion of the emergency doctors. It seems that unconscious mechanisms of repression prevent the actual realistic recording of physical and emotional stress during the emergency service by helicopter. PMID- 1932450 TI - [Pneumonia prevention in long-term mechanically ventilated patients: selective skin decontamination according to Stoutenbeek or prevention of colonization according to Unertl? A prospective randomized comparison of both treatments]. AB - In a prospective randomised study, the effects of two different colonisation prophylaxis techniques on colonisation and pulmonary infection were investigated in 40 critically ill patients with long-term ventilatory support (greater than or equal to 4 days). 20 patients were selectively decontaminated with 4 x 100 g polymyxin E, 4 x 80 mg tobramycin and 4 x 500 mg amphotericin B, administered through the gastric tube and with an antimicrobial sticky paste in the oropharynx (group I). 20 patients received 50 mg of polymyxin B and 80 mg of gentamicin dissolved in 10 ml of 0.9% saline at 6 h intervals into nose, oropharynx and stomach as well as 300 mg of amphotericin B in the oropharynx only (group II). All patients received cefotaxime systemically in the first 3 days. In group I gram-negative aerobic bacteria in the pharynx decreased from 35% to 0%, in group II from 40% to 10% and in the rectum from 80% to 61% (10% in the second week) in Group I and from 100% to 73% (33% in the second week) in group II. The decrease in gram-negative microorganisms was accompanied by an increase in the frequency of Staphylococcus epidermidis. In group I, two patients developed pneumonia and two patients urinary tract infections, in group II two patients suffered from pneumonia and 3 patients urinary tract infections. Both regimes are effective methods of prophylaxis for lowering colonisation with gram-negative aerobic bacteria and the frequency of pneumonia in patients requiring long-term mechanical ventilation. A possible selection of gram-positive bacteria must be appropriately monitored. PMID- 1932452 TI - [Transfemoral extraction of a knotted Swan-Ganz catheter using an F24 dilator]. AB - We report on the successful transfemoral extraction of a Swan-Ganz catheter twice knotted in a patient's heart. The extraction was performed with a Dormia basket and removed via a 24F dilatator which was placed in the femoral vein. The Swan Ganz catheter had been placed in a 67-year old patient after Whipple's operation. The technical procedure of the catheter removal is described and the advantages are discussed. PMID- 1932453 TI - ["MEDDOS", a computer program for constructing treatment plans in pediatric intensive care units]. AB - We attempted to facilitate the establishment of treatment regimens in paediatric intensive care units by means of a computer programme and to increase drug safety by standardization of dosage and avoidance of calculation errors. The programme has the following features: the user can enter drugs, oral nutrition and i.v. solutions into data files. Drugs and solutions can be chosen from these data files for the individual patient. Drug dosage is calculated from preselected dosages and the patient's data for individual dosage regimens. The desired intake of fluid volume and glucose can be chosen. Due to this preselection the quantity and concentration of the glucose solution is calculated. The total daily intake of electrolytes, calories, carbohydrates, protein and fat is shown on a balance sheet. Complete schedules can be saved and, if needed, restored for other patients. PMID- 1932454 TI - [Are mixtures of local anesthetics toxic as single substances? Comments on the paper by Ch. Schnorr et al.: Local anesthetic mixtures in different regional anesthesia procedures]. PMID- 1932455 TI - Health promotion revisited. PMID- 1932456 TI - Health promotion revisited. PMID- 1932457 TI - Women and children first: toward a U.S. family policy. PMID- 1932458 TI - The relationship between literacy and health. AB - In non-industrialized countries, populations with the lowest literacy rates have the poorest health status. In the United States, however, there is no published research on whether illiteracy, independently of other sociodemographic factors, is related to health status. There are numerous plausible mechanisms by which such a relationship could occur. For example, published reports indicate that most information handouts, consent forms, and other materials for patients are written at reading levels too difficult for most American adults. These and other findings may have important implications in the health care of underserved populations. Research is needed to determine the health effects of impaired literacy skills among Americans, and to develop non-literacy-dependent methods for providing patient education, obtaining informed consent, and administering diagnostic tests. PMID- 1932459 TI - Federal provision of health care: creating access for the underinsured. AB - Access to health care for the underinsured in America is a major current policy issue. Federal provision of health care has not been evaluated seriously as part of the solution to the problem despite the presence of federal health care provided to veterans, the class of Americans most completely guaranteed universal access. We first explore the arguments for and against universal access, clarifying issues but yielding no definitive solution. Then the federal health care system for veterans is used as a model for exploring problems that must be solved in a universal access plan. The discussion focuses on the effects of competition for patients and health care resources on costs, innovation, regulation, and quality. PMID- 1932460 TI - Community wellness: a group empowerment model for rural America. AB - Because answers to rural health problems no longer reside solely at the federal or state level, county Extension agents in Georgia are playing a pivotal role in helping communities empower themselves with the Community Wellness program. Community Wellness is a process-oriented program that encompasses community-based program planning; facilitates interventions based on an assessment of community specific health needs; encourages empowerment of the community; and develops a community-wide support system. County Extension agents and other leaders serve as catalysts to bring together members of the community to identify health needs, develop strategies to solve problems, and implement solutions. Four case histories describe how this model has strengthened community infrastructure, developed human capital, and created rural leadership. A discussion of barriers to implementation and lessons learned follows. PMID- 1932461 TI - Medicaid patients' access to office-based obstetricians. AB - Recent expansion of the eligibility of low-income pregnant women for Medicaid funded prenatal care may be jeopardized by undersupplies of obstetricians and gynecologists (OB/GYNs) in rural and urban low-income areas and by widely reported declines in the number of OB/GYNs willing to accept Medicaid patients. This paper examines the availability of office-based obstetric care to Medicaid patients in Illinois. We present and test a model of the determinants of Medicaid participation by private, office-based OB/GYNs that highlights the role of residential segregation and practice economics. We find that a large growth in demand for obstetrical care or the enhancement of Medicaid fees is unlikely to have a major effect on OB/GYN participation in Medicaid. We conclude that improving access will require expanding the supply of providers in underserved areas. PMID- 1932462 TI - When can animal carcinogenicity studies detect a carcinogenic risk? A comment on a paper by M.C.D. Scales and Z.E. Andrews. PMID- 1932463 TI - Effects of maternal drug addiction on the fetus. PMID- 1932464 TI - Transmission of Creutzfeldt-Jakob disease by investigative and therapeutic procedures. PMID- 1932465 TI - The use of two compatible rodent strains to improve the sensitivity of carcinogenicity studies: a data review of spontaneous rodent neoplasms. PMID- 1932466 TI - The 'law of bone transformation': a case of crying Wolff? PMID- 1932467 TI - The occurrence and functions of ultradian rhythms. AB - Ultradian oscillations with periods between 5 min and 4 h have been described in cell-free extracts, single-celled eukaryotes, cultured cells and embryos. Whereas some of these potentially oscillatory systems (e.g. glycolysis) may only exhibit this type of behaviour rarely if at all in vivo, other ultradian oscillators in lower eukaryotes are rhythms and probably have timekeeping functions. Rhythms with ultradian periods of 10 min to 20 h in oxygen consumption and carbon dioxide production have also been studied in endotherm animals: these rhythms may be modified by variations of environmental parameters and by circadian and infradian synchronizers. Interspecies and interstrain differences strongly suggest that these rhythms are endogenous and have a genetic origin. We suggest that the temporal organization of biochemical and physiological processes facilitates optimization of thermodynamic maintenance of the organism within the random fluctuations of its physicochemical environment and contributes to genetic selection. PMID- 1932468 TI - [The contribution of a research center to the development of research awareness and research competence in nursing]. PMID- 1932470 TI - [The value of disgust in the experience of nursing personnel]. PMID- 1932469 TI - [Assessment of pain in school children]. PMID- 1932471 TI - [Emotional work--a new dimension for nursing research]. PMID- 1932472 TI - [Care against the patient's will. An ethical-moral question]. PMID- 1932473 TI - [Patients interpret problematic hospital experiences]. PMID- 1932474 TI - [Working conditions and job satisfaction of nurses in the night shift]. PMID- 1932475 TI - [Bibliotherapy: reading as an aid in facing one's illness]. PMID- 1932476 TI - [Development of professional activities of nurses in practical courses in nursing schools]. PMID- 1932477 TI - [Research in the field of primary care from the viewpoint of the nursing profession]. PMID- 1932478 TI - Review article: prevention and treatment of travellers' diarrhoea. AB - Travellers' diarrhoea is a common problem worldwide and is likely to continue to increase with the expansion of foreign travel. ETEC is the most frequently isolated enteropathogen although other bacteria, parasites and viruses may be important, depending on the geographic location. New pathogens may well emerge in the future. Prevention must be the ultimate goal but while awaiting effective vaccines we must be content with the traditional dietary advice and its often unpalatable and unacceptable restrictions. Antibiotic prophylaxis is clearly effective but for the present should be restricted to high risk individuals and in those in whom any disruption of a short stay would be critical. For those taking antibiotic prophylaxis advice, as always, should be given regarding the possible adverse effects. Concern about the emergence of resistant strains may be less with the new 4-fluoroquinolone antibiotics. Alternatives for prophylaxis include bismuth subsalicylate which is safe and not an environmental hazard. We must await developments in the Lactobacillus sp. story to see whether the use of probiotics have any role in the prevention of travellers' diarrhoea. Antimotility agents have no place in prophylaxis. The cornerstone of treatment of travellers' diarrhoea is the maintenance of fluid and electrolyte balance. It is particularly important in infants and young children and should be given in the form of oral glucose-electrolyte solutions of which there are many effective preparations. A variety of antibiotics are now known to reduce the duration of travellers' diarrhoea but there is still concern about the risk of therapy for what is usually a minor illness of inconvenience. However, when the loss of 1 or 2 days during a short visit is critical, one could opt for a short course of antibiotics (trimethoprim-sulphamethoxazole, or a 4-fluoroquinolone for 3 days or less) in combination with an antidiarrhoeal trimethoprim alone agent such as loperamide. PMID- 1932479 TI - Inhibition of gastrin- and histamine-stimulated gastric acid secretion by gastrin and cholecystokinin antagonists in the rat. AB - The gastric acid inhibitory activities of a peptide-like gastrin receptor antagonist, Boc-beta Ala-Trp-Leu-Asp-O(CH2)2-Ph-4-F (CH-486), a nonpeptide gastrin/CCK-B antagonist (L-365,260), and a CCK-A antagonist (L-364,718), were investigated in the gastric lumen-perfused anaesthetized rat. A single i.v. injection of CH-486, 100 mumol/kg, reduced acid secretion stimulated by pentagastrin, 15 micrograms kg/h, to unstimulated levels, with no recovery within 50 min. Histamine-, 0.1 mumol kg/min, and carbamylcholine-, 0.1 mg kg/h, stimulated acid secretion were also reduced to unstimulated levels by CH-486, 100 mumol/kg, although with these latter two stimulants the inhibition was transient. L-365,260 and L-364,718, 10 mumol/kg, significantly inhibited both pentagastrin- and histamine-stimulated acid secretion, the latter again transiently. We conclude that the non-selective nature of the gastric acid inhibitory activity of gastrin antagonists might allow novel approaches to control gastric acid secretion in peptic ulcer disease. PMID- 1932480 TI - The effect of portal hypertension on indomethacin-induced small intestinal ulceration in the rat. AB - The purpose of this study was to determine whether portal hypertension potentiates intestinal ulceration induced by indomethacin. Portal hypertension was produced in male Sprague-Dawley rats by two-staged ligation of the portal vein. Sham-operated rats were used as controls. The rats were given 20 mg/kg of indomethacin intragastrically, 7 and 14 days, respectively, after complete portal vein ligation. Forty-eight and 72 h after indomethacin, portal pressures were measured and the whole small intestine removed for quantitative measurement of the percent of the mucosa ulcerated by computerized image analysis. There were no differences in the area of ulceration between the portal hypertensive and sham operated rats at either 7 or 14 days, despite the presence of significant portal hypertension. Portal hypertension does not appear to potentiate small intestinal ulceration induced by indomethacin in rats. PMID- 1932481 TI - Comparison of rat and human intestinal perfusion models for assessing efficacy of oral rehydration solutions. AB - The optimal composition for oral rehydration solutions remains controversial. Animal models have been used to assess the efficacy of new formulations but the relevance of these studies to the handling of oral rehydration solutions in human intestine during diarrhoeal disease states remains uncertain. Using steady state perfusion techniques we have compared water and solute transport from a variety of oral rehydration solutions in both the entire rat small intestine and in the human jejunum. Overall the pattern of water, sodium and glucose absorption was similar from the three oral rehydration solutions tested, indicating close parallelism between the two models despite the species and methodological differences. Although the relationship between the findings of these studies to the handling of oral rehydration solution in diarrhoeal disease states remains uncertain, we believe they do support the view that animal models may have a part to play in the preliminary screening of oral rehydration solutions before clinical trial. PMID- 1932482 TI - Effects of low-dose cimetidine on nocturnal acid secretion in healthy subjects. AB - The effects of 100 mg and 200 mg bedtime doses of cimetidine on nocturnal gastric acid secretion were examined in nine healthy subjects in a double blind, placebo controlled, randomised three way crossover study. Treatment was given at 23.00 hours and the gastric contents continually aspirated from midnight until 07.00 hours the following morning. Hourly aliquots were analysed for pH and acid output. Relative to placebo the 100 mg and 200 mg doses of cimetidine respectively increased mean pH by 2.22 and 2.63 units/h (P less than 0.001) with mean acid output decreasing by 0.95 and 0.98 mmol/h (P less than 0.001). Whilst mean pH was higher and mean acid output was lower for 200 mg cimetidine compared to 100 mg cimetidine the difference was not statistically significant. Mean hourly pH was consistently above pH 3 for 100% of the time for both doses of cimetidine whereas mean pH failed to reach this value at anytime on placebo. Low doses of cimetidine taken at bedtime effectively reduced nocturnal gastric acid secretion in healthy individuals. PMID- 1932483 TI - Evaluation of an enteric-coated naproxen pellet formulation. AB - An enteric-coated, pellet formulation of naproxen has been evaluated in eight healthy subjects. Each volunteer was dosed with 153Sm-labelled, enteric-coated pellets on two occasions, once whilst fasted and once after breakfast. Gastrointestinal transit was followed using gamma scintigraphy and drug absorption compared with that from uncoated naproxen pellets dosed on a separate occasion. The pH in the stomach and intestines was monitored using radiotelemetry capsules. Gastric emptying was delayed by dosing after breakfast, but small intestinal transit of the enteric-coated formulation was the same on both occasions. The highest pH recorded from the stomach was 4.0 and in all subjects the pH rose to at least 7.3 in the small intestine. The onset of drug absorption was fastest from the uncoated formulation and slowest from the coated pellets taken after breakfast. The total amount of drug absorbed was the same on all three occasions. PMID- 1932484 TI - Controlled study of the effects of intravenous famotidine on intragastric pH in bleeding peptic ulcers. AB - As blood coagulation and platelet aggregation are abolished at pH less than 5.4 the failure of antisecretory drugs to promote haemostasis in bleeding peptic ulcers may reflect inadequate pH control. This study examined the ability of famotidine, a potent, long-acting H2 blocker to maintain intragastric pH above 5.4 in patients presenting with bleeding peptic ulcers. Twenty patients with acute upper gastrointestinal haemorrhage confirmed endoscopically to be related to peptic ulceration (17 duodenal, 3 gastric ulcers), were entered into the study within 24 h of presentation. Each patient was randomly allocated to receive either intravenous famotidine (n = 10) administered as a 10 mg bolus followed by a constant infusion of 3.2 mg/h or similarly administered placebo (n = 10). All patients remained fasted over the 22-h study period. Their median intragastric pH values ranged from 6.8 to 7.9 (median 7.1) in the famotidine group and from 1.1 to 6.9 (median 1.6) in the placebo group (P less than 0.001). Over this same period intragastric pH was greater than 6 for 64%-100% (median 98%) of the recording time in the famotidine group compared with 0%-93% (median 13%) in the placebo group (P less than 0.001). We conclude that intravenous famotidine can maintain intragastric pH greater than 6 in fasting patients with acute upper gastro-intestinal bleeding from peptic ulceration. This provides a rational basis for further studies assessing its clinical efficacy in such patients. PMID- 1932485 TI - Short report: a double-blind placebo-controlled trial of omeprazole on characteristics of gastric emptying in healthy subjects. AB - The aim of the study was to investigate a possible effect of omeprazole on the characteristics of the gastric emptying of liquid and solid in healthy subjects. The study was performed as a double-blind crossover study and the gastric emptying studies were performed after 10 days of treatment with placebo or omeprazole 40 mg o.m. Omeprazole was without effect on the characteristics of liquid emptying or the lag phase of solid. It does, however, decrease the emptying rate of solid as the omeprazole group had a median half-time duration of the linear emptying period which had twice the duration of the corresponding figure in the placebo group. PMID- 1932486 TI - [Apolipoproteins and atherosclerosis]. PMID- 1932487 TI - [Immunoregulating phenomena in patients with alcoholic cirrhosis]. AB - Several immunologic changes, both humoral and cellular, have been described in patients with post-alcoholic cirrhosis. One of these changes was a polyclonal hypergammaglobulinemia which can be produced by a failure in the immunoregulation dynamics. The number of leukocytes, as well as lymphocytic population and subpopulation, did not prove significant differences between healthy people and patients. The seric immunoglobulin showed an increase of IgG in cirrhotics. The synthesis of immunoglobulins "in vitro" showed increased productions in cirrhotics; this being spontaneous in IgA and induced by pokeweed in the case of IgG and IgA. PMID- 1932489 TI - [Cardiovascular risk factors in an Arab and Hispanic working population]. AB - 318 records of male workers, 169 Spanish and 149 Arab were retrospectively studied in 1987 at the "Gabinete de Seguridad e Higiene en el Trabajo" (Council for Safety and Hygiene in the Workplace) in Ceuta in order to prove the hypothesis that 2 different ethnic groups living in the same geographic area have a non-equal distribution of cardiovascular risk factors. The Spanish group showed a higher prevalence in blood hypertension, diabetes, glucose intolerance, obesity and alcohol intake, compared to the Arab group. Smoking and high levels of seric cholesterol were similar in both groups, however, medium levels of seric cholesterol were lower in the Arab group. Family histories of cardiovascular disease were very rare in the latter mentioned group. These observations suggested a major predisposition to ischemic cardiopathy in the Spanish group. PMID- 1932488 TI - [Thrombogenic factors in the elderly. Evaluation of the plasma concentrations of thromboxane B2 and antithrombin III]. AB - The aim of this study is to prove the existence of a major tendency of platelet aggregation in elderly patients compared to medium-aged adults and, also, to detect whether it is affected by the presence of diabetes mellitus. Plasmatic concentrations of B2 thromboxane (TXB2) and antithrombin III (AT III) were determined in 73 elderly patients of both sexes; 56 without metabolic disease known (Group a) and 17 diabetic patients, 7 type I (Group bI) and 10 of type II (Group bII); and 12 healthy adults (control group). Medium plasmatic concentration of TXB2 was significantly higher (p less than 0.001) in Group a (55 +/- 14 ng/ml) compared to the control group (37 +/- 9 ng/ml) and there was no difference between Group bI (53 +/- 19 ng/ml) and bII (57 +/- 15 ng/ml). No variations were noted in ATIII concentration between the adults (27.4 +/- 2.3 mg/dl) and elderly patients (a = 29.6 +/- 4.4, bI = 29 +/- 2.6, bII = 31.2 +/- 5.9 mg/dl). In elderly patients, there appears to be a state of platelet pro aggregation without influence of any risk factor, such as diabetes. This could explain the thrombogenic tendency of this age group. PMID- 1932490 TI - [Qualitative study of proteinuria in diabetic nephropathy]. AB - The qualitative features of the proteinuria in diabetic nephropathy was studied by carrying out tests of clearance quotient of IgG and albumin in diabetic patients. Diabetic patients with micro and macroalbuminuria showed a major selectivity of proteinuria in relation to normoalbuminuric patients; this suggests a loss of anions at glomerular level. PMID- 1932491 TI - [Mortality in the under-65 years of age in a teaching internal medicine service]. AB - The reports of patients under 65 years of age who died during the period 1982 to 1988 at an Internal Medicine Department in a University Hospital were analysed in a transversal study. There were 927 deaths, 815 being evaluable, and 160 (19.63%) of the patients were under 65 years old. The group in question had multiple diseases and admissions (15.72%). The most frequent diseases observed were neoplasia (31.64%), cirrhosis (17.08), ischemic cerebrovascular disease (11.39%), pneumonia (11.39%) and renal insufficiency (11.39%). Terminology such as cardio respiratory arrest and "probably, possible or not confirmed" were found in 30.37% of the reports. PMID- 1932492 TI - [Myocardial sarcoidosis treated with implantable defibrillator]. AB - We describe the case of a 33 year old diabetic patient with systemic sarcoidosis who, prior to this, had episodes of myocardiac alterations such as ventricular tachycardia, which partially improved with steroid therapy. She eventually needed a defibrillator-pacemaker implant which serves to reduce the high risk of sudden death in this type of patient. The myocardiac biopsy did not show granuloma. The diagnosis, prognosis and treatment of cardiac sarcoidosis are commented on, as well as its association to diabetes mellitus, such as in this case. PMID- 1932493 TI - [Wegener's granulomatosis. Apropos of a new case and review of the literature]. AB - A case of Wegener's granulomatosis (WG) is presented, high-lighting the long-term evolution of affliction of the upper airways without diagnosis, as well as the rapid evolution after detection of the rest of the compounds of the syndrome. We show the difficulties in making a differential diagnosis and the clinical improvement with immunosuppressor treatment. PMID- 1932494 TI - [Treatment with indomethacin for the control of the metabolic disorder caused by a villous adenoma of the rectum]. AB - A 79 year old patient with a previous history of 10 months of mucous diarrhea is admitted due to pre-renal insufficiency, hyponatremia, hypokalemia and metabolic alkalosis secondary to rectal villous adenoma. The volume of the rectal discharge was 2.500 cc/day. Sodium level of the rectal secretion was 145 mEq/L and potassium 20 mEq/L. E2 prostaglandin: 1500 pg/ml. After hydroelectrolytic treatment, a PG synthetase inhibitor (indomethacin) was added to a dosage of 25 mg q/d PO. Rectal discharge was reduced to 500 cc/day, as well as sodium and prostaglandin levels. It has been proved that the use of PG synthetase inhibitors can facilitate the preparatory metabolic control in patients with villous adenoma. PMID- 1932495 TI - [Parinaud's oculo-glandular syndrome secondary to cat-scratch disease]. AB - A 56 year old patient with an oculo-glandular syndrome of Parinaud, secondary to a cat scratch disease, is presented. The biopsy of the palpebral conjunctiva and parotid gland showed a non-caseous granulomatosis. The patient met the diagnosis criteria for cat scratch disease and, after treatment with a low dosage of steroids, showed a good evolution. PMID- 1932496 TI - [Respiratory distress and multiple organ failure after intravesical instillation of BCG]. AB - A case of probable hypersensitivity reaction with multi-organic failure, following bladder installation of BCG, in a male with a diagnosis of bladder carcinoma is presented. The patient developed respiratory, renal and liver failure as well as leukocytosis, thrombopenia and an increase in muscular enzymes. It was resolved with hemodynamic support. The rare complication, occasionally described in medical literature and its probable pathogenic mechanisms are discussed. PMID- 1932497 TI - [Value of fibronectin in the pathology of the respiratory system]. PMID- 1932498 TI - [Non-infectious pulmonary complications in AIDS]. PMID- 1932499 TI - [Primary perimyocarditis caused by Mycoplasma pneumoniae]. PMID- 1932500 TI - [Rhabdomyolysis and renal insufficiency as complications of acute gastroenteritis caused by salmonella enteritidis]. PMID- 1932501 TI - [Acute pseudo-obstruction of the colon. Report of a new case]. PMID- 1932502 TI - [Usefulness of flumazenil in the treatment of acute alcoholic intoxication]. PMID- 1932503 TI - [Polymyalgia rheumatica and pericardial effusion]. PMID- 1932504 TI - [Hypophosphatasia in the adult: description of a case]. PMID- 1932505 TI - [Arterial hypertension secondary to primary hyperaldosteronism caused by an adrenal adenoma]. PMID- 1932506 TI - Analyses of bronchoalveolar lavage fluid (BALF) in MRL-lpr/lpr mice. AB - We performed bronchoalveolar lavage (BAL) in MRL-lpr/lpr (MRL/l) and MRL- +/+ (MRL/n) mice and evaluated various cellular and humoral components of the bronchoalveolar lavage fluid (BALF) to clarify the pathogenic mechanism of pulmonary fibrosis in MRL/l mouse. The numbers of macrophages, neutrophils and lymphocytes, N-Acetyl-beta-glucosaminidase (beta-NAG), and fibronectin increased in the BALF from MRL/l mice than that from MRL/n mice, but no significant differences were observed in total protein, beta-glucuronidase, acid phosphatase, or phospholipid level. Increased fibronectin level in the BALF from MRL/l mice may be related with pathogenesis of pulmonary fibrosis. PMID- 1932507 TI - Activation of murine autoreactive b cells by interleukin 1-like factors released from synovial inflammatory cells of rheumatoid arthritis patients. AB - The effect of interleukin 1 (IL-1)-like factor(s), produced by cells isolated from the synovial fluids of rheumatoid arthritis (RA) patients, on an in vitro murine model of spontaneous autoimmunity, i.e., the development of plaque-forming cells (PFC) to bromelain-treated mouse red blood cells (Br-MRBC) in mouse peritoneal cell (PC) cultures, has been investigated. It has been found that IL-1 containing culture supernatants from cells isolated from joint fluids of RA patients, as well as recombinant IL-1, determine a marked increase in anti-Br MRBC PFC development. Moreover, factor(s) of 10-20 KD molecular weight, with IL-1 like biological activity, capable of increasing the anti-Br-MRBC PFC development in mouse PC cultures, have been demonstrated in joint fluids from RA patients. The finding that synovial inflammatory cells produce factors that activate autoreactive B cells further supports the role of autoimmunity in the pathogenesis of rheumatoid arthritis, as self-perpetuing disorder. PMID- 1932508 TI - Pristane induced arthritis. II. Genetic regulation in F1 hybrid mice and cellular immune abnormalities following pristane injection. AB - Pristane-induced arthritis was investigated in DBA/1, DBA/2, and BALB/c mice, and F1 hybrid mice generated from inter-crosses between these strains. The incidence of disease in F1 hybrid mice was significantly lower than the susceptible parental strains (DBA/1 and BALB/c), and resistance to arthritis was observed in both DBA/2 mice and the (DBA/2 x BALB/c) F1 hybrid mice. Several cellular immune abnormalities were observed in pristane-injected DBA/1 mice. Con A mitogen responses were depressed following pristane injection, and a functional suppressor cell population was detected. Delayed type hypersensitivity responses to type II collagen were observed in pristane injected mice. The intraperitoneal injection of pristane appears to alter immune regulation and induce autoimmune responses to connective tissue components. PMID- 1932509 TI - Insulin dependent diabetes mellitus hypothesis of autoimmunity. PMID- 1932510 TI - The structure of human MHC class II genes. AB - The class II molecules of the human major histocompatibility complex bind intracellularly processed peptides and present them to T-helper cells. They therefore have a critical role in the initiation of the immune response. A salient feature of the class II molecules is their polymorphism. It has been shown that some autoimmune diseases are associated with certain class II alleles. This article reviews the basic structural features of class II molecules, and the genes encoding them as well as mechanisms governing the development of their extraordinary polymorphism. PMID- 1932511 TI - Ageing, autoantigen specific-Ts cells, involution of the thymus, autoimmunity and autoimmune diseases. PMID- 1932512 TI - Soluble HLA-DR molecules in patients with HLA class II versus class I associated disorders. AB - HLA genes have been identified as key genetic factors contributing to many chronic diseases characterized by autoimmune features. The role of HLA encoded molecules in the pathogenesis of these diseases is unresolved. We have now analysed soluble HLA-DR molecules circulating in the serum of patients with different autoimmune diseases and have defined parameters controlling serum levels. Patients with HLA-DR associated diseases were characterized by elevated serum concentrations of HLA-DR molecules and were clearly distinct from patients with HLA-B27 associated disorders. We did not find evidence for a correlation between disease activity, laboratory abnormalities and elevated serum concentrations of soluble HLA-DR molecules. Studies in normal individuals indicated that soluble HLA-DR molecules are at least partially regulated by the HLA haplotype. Highest serum concentrations were found in individuals carrying the HLA-DR3 or HLA-DR4 haplotype raising the possibility that the phenomenon of HLA-disease association reflects differences in the genetic control of soluble HLA-DR molecules. Interferon-gamma treatment caused an increase in serum concentrations of soluble HLA-DR molecules, whereas a decrease of circulating HLA DR molecules was associated with an immunosuppressive with cyclosporine A. These data suggest that the patient's immunoresponsiveness represents a second important mechanism controlling circulating HLA-DR molecules. PMID- 1932513 TI - Structural and functional characterization of HLA-DR molecules circulating in the serum. AB - HLA molecules are highly polymorphic glycoproteins with a single binding site for immunogenic peptides. The complex formed by HLA-DR molecules and peptides is the entity specifically recognized by the antigen receptor of CD4+ helper T lymphocytes. This biological function has been linked to the constitutive cell surface expression of HLA molecules on antigen-presenting cells which provide immunogenic peptides through denaturation or fragmentation of antigen. Here, we report that HLA-DR molecules can be identified in a soluble form circulating in the serum. Biochemical characterization and recognition of such soluble HLA-DR molecules by a monoclonal antibody reactive to conformational determinants on the alpha-beta HLA complex indicates that they are circulating as intact heterodimers. Upon activation, human T cells and B cells release soluble HLA-DR molecules. The expression and secretion of HLA-DR by T lymphocytes is greatly enhanced in the presence of macrophages indicating that the production of HLA-DR molecules might be regulated and controlled through factors derived from antigen presenting cells. An alloreactive human T cell clone can be stimulated to proliferate in response to soluble HLA-DR molecules purified and enriched from serum suggesting that the soluble form of the natural ligand of the T cell receptor might have immunoregulatory functions. PMID- 1932514 TI - Onset and regulation of anti-lamin B autoantibody production is independent of the level of polyclonal activation. AB - Anti-lamin B autoantibodies are associated with both systemic lupus erythematosus (SLE) and autoimmune liver disease. We examined the possibility that the underlying clinical feature in patients with anti-lamin B autoantibodies might be chronic autoimmune liver disease, and whether the hypergammaglobulinemia present in both disorders is involved in generating anti-lamin B autoantibodies. A lamin B fusion protein (MLB1), consisting of amino acids 77-533 of lamin B fused to TrpE, was used to screen sera from 84 patients with SLE for anti-lamin B autoantibodies. 3/4 prototype human lamin B antisera, 5/84 SLE sera (6%), and 0/30 sera from healthy individuals reacted with MLB1 on immunoblots at a 1:500 dilution. Of the 9 anti-lamin B autoantibody positive patients studied, all but 1 fulfilled at least four ARA criteria for SLE. None of the patients displayed evidence of chronic autoimmune liver disease, suggesting that autoimmune liver disease is not strongly associated with anti-lamin B antibodies in SLE. In SLE, as in "lupoid hepatitis", anti-lamin B autoantibodies are often produced transiently during periods of increased disease activity. Although polyclonal hypergammaglobulinemia is also associated with increased activity of both diseases, anti-lamin B autoantibody production in 2 patients was independent of total immunoglobulin levels, antibodies to irrelevant proteins, and production of some other autoantibodies. Thus, polyclonal activation is insufficient to explain either the initiation or regulation of anti-lamin B autoantibody production, supporting the hypothesis that antinuclear antibodies are antigen-selective. PMID- 1932515 TI - Experimentally-induced autoimmune myocarditis: production of heart myosin specific autoantibodies within the inflammatory infiltrate. AB - Immunization with cardiac myosin in complete Freund's adjuvant (CFA) induces severe autoimmune myocarditis in A H-2 congenic mouse strains. The disease shares a variety of characteristics with Coxsackie-virus B3 (CB3)-induced myocarditis and is strongly associated with high-titered autoantibodies to cardiac myosin. Using the spot ELISA-technique, we demonstrate here that in cardiac myosin immunized mice myosin autoantibodies were not only produced within the spleen, but also at the site of the autoimmune attack, i.e., within the inflammatory heart infiltrate. At the level of single plasma cells we further showed that a substantial part of the myosin autoantibodies was specific for the cardiac myosin isoform, thereby supporting previous serologic data. The finding that cells of the inflammatory heart infiltrate significantly contribute to autoantibody production might explain why the occurrence of high-titered myosin autoantibodies is restricted to mice which develop the disease. PMID- 1932516 TI - Immunization with inactivated lactate dehydrogenase-elevating virus followed by virus infection favors the selection of hybridomas synthesizing antibodies cross reacting with intermediate filaments and the LDV envelope protein VP3. AB - Autoantibodies against Golgi antigen and a tumor surface antigen (TSA) of aetiologically unrelated murine cell transformants that develop in immunocompetent mice as early as 6-7 days after treatment with live LDV do not appear after immunization with inactivated virus. However, combination of immunization with inactivated LDV and treatment with live LDV enhances the production of autoantibodies against determinants of intermediate filaments. The basis of the stimulation of this group of autoantibodies is at least in part due to antigenic mimicry between the envelope protein VP3 of LDV and determinants of intermediate filaments, since a panel of monoclonal antibodies cross-reacts with both. PMID- 1932517 TI - Immunological and molecular characteristics of the thyroid peroxidase autoantigen. PMID- 1932518 TI - Mechanisms of resistance to autoimmune disease induced by T-cell vaccination. PMID- 1932519 TI - Preferential proliferation of anti-DNA producing cells of NZB mice in NZB.xid recipients. AB - B cells from autoimmune NZB mice were transferred into unmanipulated non autoimmune NZB.xid mice. The number of antibody-producing cells against various antigens in recipient mice was monitored at varying time after cell transfer using ELISPOT assay. NZB B cells producing antibody against all antigens we examined were able to proliferate in NZB.xid mice, which supports the idea of polyclonal B cell activation. However, anti-DNA producing cells proliferated most rapidly, and anti-BrMRBC producing cells proliferated more rapidly than B cells of other antigenic specificities. The percentage of anti-DNA producing cells in total immunoglobulin-producing cells increased over time whereas the percentage of anti-ovalbumin producing cells kept the same level. This indicates directly the preferential proliferation of NZB anti-DNA producing cells in NZB.xid mice. The result shows the responsibility of antigen-specific stimulation or activation on autoimmunity in the context of polyclonal B cell activation. PMID- 1932520 TI - The expression and regulation of class II antigens in normal and inflammatory bowel disease peripheral blood monocytes and intestinal epithelium. AB - Elevated constitutive expression of major histocompatibility (MHC) class II antigens occurs in the enterocytes of patients with IBD. It has been suggested that this aberrant expression of class II molecules may play a role in the pathogenesis of IBD. We examined two possible reasons for such a finding. 1) Heightened sensitivity of IBD enterocytes to endogenous gamma interferon (gamma IFN) and 2) enhanced endogenous secretion of gamma interferon by intestinal cells in close proximity to the enterocytes (lamina propria lymphocytes). Constitutive and gamma interferon stimulated HLA-DR and DP density on intestinal epithelial cells (IEC) and peripheral blood monocytes (PBM) from UC patients (IEC n = 13; PBM n = 20), CD patients (IEC n = 14; PBM n = 18) and non-IBD controls (IEC n = 12; PBM n = 20) were measured via flow cytometry (mean channel fluorescence). gamma IFN production by PHA stimulated and unstimulated lamina propria lymphocyte (LPL) cultures of UC patients (n = 11) CD patients (n = 8) and non-IBD controls (n = 11) was measured using a vesicular stomatitis virus/WISH cell bioassay. We found significantly greater gamma IFN secretion by IBD-derived PHA stimulated LPL than from non-IBD stimulated controls (CD = 39.4 +/- 12.4u; UC41.5 +/- 6.8u; NL = 22.4 +/- 8.3u, p less than 0.05) while gamma IFN induced HLA-DR and DP upregulation was no greater in IBD-derived IEC and PBM than in non-IBD controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932521 TI - Activation of cytotoxic cells by syngeneic prostate antigens in experimental autoimmune vesiculo-prostatitis. AB - In our experimental model of autoimmune vesiculo-prostatitis, obtained by immunization with syngeneic male accessory glands (MAG) and complete Freund's adjuvant, the presence of specific autoreactive cells with cytotoxic activity against prostate antigens was studied. The specific cytotoxicity generated in MAG immunized rats was tested using 51Cr labelled syngeneic prostate cells or labelled chicken erythrocytes coated with specific antigens (MAG homogenate or chromatographic fractions from prostate homogenate) which were used as target cells in a medium free of complement. The addition of spleen sensitized cells to prostate cells suspension produced a significant release of 51Cr in regard to normal effector cells (11.87 +/- SE 1.12 versus 1.5 +/- 0.75). Similar results were obtained when MAG-coated erythrocytes were used as target cells (10.87 +/- SE 0.62 versus 1.50 +/- 0.25). Depletion of T but no B or adherent-cells was shown to abolish the lytic effect indicating that MAG immunization provides determinants which are recognized by sensitized T-cells on cells of the prostate gland where the most severe tissue alterations were previously observed. Erythrocytes coated with chromatographic fractions obtained from prostate homogenate were used to identify the antigens triggering the lytic effect. It was demonstrated that two fractions (FI and FII) functioned as in vivo sensitizing antigens as well as in vitro activating antigens for themselves. The restimulation in vitro of sensitized cells with purified prostate fractions induces an additional lytic effect suggesting that an expansion of effector cells may take place after contacting the antigens at the prostate site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932522 TI - Antibodies to vascular heparan sulfate proteoglycan in patients with systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease which involves the basement membranes of blood vessels in multiple organs. An important component of the microvasculature is vascular heparan sulfate proteoglycan (HSPG). In this study, we investigated the presence in SLE and other immune disease sera of autoantibodies to purified vascular HSPG. Our data demonstrate that antibody to HSPG is found primarily in SLE sera, and not in sera from controls or patients with other immune diseases. The titer of antibody to HSPG correlated with complement depletion in SLE sera. Antibody to HSPG was frequently found in high titer in SLE patients with renal and neurologic involvement. These studies indicate that our assay for antibody to vascular HSPG detects a pathologically relevant autoantibody in SLE sera. The implications of our findings for pathogenesis of vascular autoimmunity are discussed, including the relationship of anti-vascular HSPG antibody to anti-DNA and antiphospholipid antibodies. PMID- 1932523 TI - Immunoglobulin isotypes of C57BL/6 nu/nu, lpr/lpr mice. Lack of direct intrinsic effect of the lpr gene on B cell hyperactivity. AB - The absolute concentrations of mouse immunoglobulin (Ig) heavy chain isotypes were determined by specific ELISAs in the serum of C57BL/6 (B6) mice doubly homozygous at the nude (nu) and the lymphoproliferation (lpr) locus (B6 nu, lpr mice), and compared with normal B6 nu mice. The distribution and the absolute concentrations of all Ig isotypes were found to be very similar in B6 nu, lpr and B6 nu mice, for both sexes and with similar increases in titers with ageing. Thus, the major part of the severe autoimmunity and hyperglobulinemia characteristic of the lpr syndrome of euthymic B6 lpr mice, including their elevated titers of thymus-independent IgM and IgG3 isotypes, is abrogated by the nude mutation, an effect of which is the lack of thymus differentiation. Though a postulated intrinsic activity of the lpr gene directly on B cell hyperactivity cannot be discarded, its expression would then require the presence of either the thymus or of T cells or of other cells or factors whose expression is also abrogated by the homozygosity at the nude locus. PMID- 1932524 TI - Enzymes as targets for autoantibodies in human autoimmune disease: relevance to pathogenesis? PMID- 1932525 TI - Autoantibodies against polynucleotides and proteins. Report of a British Society of Immunology Workshop held om 13 September 1990 in Edinburgh. PMID- 1932526 TI - Detection of protein C deficiency during oral anticoagulant therapy--use of the protein C:factor VII ratio. AB - Laboratory diagnosis of protein C deficiency is complicated by the fact that many patients referred for investigation are already being treated with oral anticoagulants. Protein C and factor VII have similar half lives and by using the protein C:factor VII ratio we hoped to be able to detect protein C deficiency in patients receiving oral anticoagulants. We have studied activity levels of protein C and factor VII to produce protein C:factor VII activity ratios in 105 patients receiving oral anticoagulants, 42 normal subjects, and nine patients with known inherited protein C deficiency. The mean ratios for these groups were 1.38, 1.12 and 0.63 respectively. In patients receiving oral anticoagulants, the protein C level showed a poor correlation with the international normalized ratio (INR) value. Reference ranges for protein C at different levels of anticoagulation were therefore considered unsuitable for the identification of inherited protein C deficiency. Five patients with inherited protein C deficiency were studied with and without oral anticoagulation; their protein C:factor VII ratios remained relatively unchanged, despite alterations in the level of the individual proteins. These results suggest that measurement of the protein C:factor VII ratio may help to identify patients with inherited protein C deficiency whilst on oral anticoagulants. PMID- 1932527 TI - Fibrinogen Kanazawa: a congenital dysfibrinogenaemia with delayed polymerization having a replacement of proline-18 by leucine in the A alpha-chain. AB - Congenital dysfibrinogenaemia was found in a 39-year-old female and her two children. The proposita, apparently heterozygous for this abnormality, had no episode of bleeding or thrombosis. The abnormal fibrinogen showed normal release of fibrinopeptides A and B but impaired polymerization of the fibrin monomer. Amino acid sequence analysis of the whole A alpha-chain isolated from fibrinogen Kanazawa showed a substitution of Leu for Pro at position 18 in the A alpha chain. This substitution was corroborated by the analysis of the amino acid sequence which demonstrated the lysyl endopeptidase peptides derived from the A alpha-chain of fibrinogen Kanazawa. The minimal genetic exchange responsible for this substitution was a C----T transition in the middle position of the Pro codon. We conclude that Pro-18 in the A alpha-chain is crucial for the polymerization of the fibrin monomer. PMID- 1932528 TI - Chromogenic substrate assay of extrinsic pathway inhibitor (EPI): levels in the normal population and relation to cholesterol. AB - A two-stage chromogenic substrate assay was standardized to measure extrinsic pathway inhibitor (EPI) activity in plasma and serum samples. In the first stage, diluted plasma or serum (0-0.8%) was incubated with factor VIIa (25 pM), tissue thromboplastin (tissue factor, TF, 1% v/v) with excess binding sites for factor VIIa, and factor Xa (0.8 nM). In the second stage, excess factor X and chromogenic substrate were added as substrate for residual TF/factor VIIa catalytic activity. Heating the samples at 56 degrees C for 15 min before assay removed greater than 95% of the factor VII amidolytic activity of the samples, defibrinated the plasma, and produced only slight reduction of EPI activity. The coefficient of variation for the same sample assayed on different days was 8.7 10.6% and the intra-assay coefficient of variation was 5.0%. Addition of anti-EPI immunoglobulin to normal plasma completely abolished the EPI activity of the sample. EPI activity was stable in plasma samples stored at -20 degrees C, but in serum, some samples lost greater than 50% activity after 3 months at -70 degrees C. Median EPI activity of umbilical cord blood was 45% (range 33-93%). In a cohort of healthy blood donors (n = 176) EPI activity was significantly correlated with age; the regression line was y = 68% + 0.60x (r = 0.39). The approximated standard deviation for the regression line was 17.9% and the age adjusted reference limits were determined. Equal levels were seen in males and females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932529 TI - Immunogold labelling of human von Willebrand factor adsorbed to collagen. AB - von Willebrand factor (vWF) mediates adhesion of platelets to the exposed subendothelium at sites of vascular injury. This function is expressed through binding of vWF to both collagen and receptors on the platelet membrane. We have developed a new method using immunogold staining and electron microscopy, permitting visualization of human vWF adsorbed to collagen fibrils. The electron micrographs revealed strings of gold beads reflecting the polymeric structure of vWF. Our data showed dramatic differences in the binding of vWF to collagens of different sources: high binding density was observed using a collagen preparation isolated from aortic tissue whereas colloidal gold was virtually absent from tendon collagen. Using the immunogold labelling method we demonstrated that high shear rate enhanced vWF binding to aortic collagen. PMID- 1932530 TI - Circadian variation of endothelial cell function, red blood cell deformability and dehydro-thromboxane B2 in healthy volunteers. AB - There is a circadian variation in the time of onset of thrombotic disorders. The thrombotic tendency of blood is influenced by many factors including complex interactions between endothelial cells, platelets and red blood cells. We studied the circadian variation of various indices of these cells' functions in 10 young healthy male volunteers. Six blood samples were collected at 4 h intervals from 12.00 until 08.00 the following morning. The volunteers carried out normal daily activities until 00.00 at which time they went to bed. They remained in bed until 08.00 the following morning. The following were measured on each sample: plasma factor VIII von Willebrand factor antigen (FVIII vWF Ag), tissue plasminogen activator activity (tPA), plasminogen activator inhibitor (PAI), prostacyclin stimulating factor (PGI2 SF), fibrinopeptide A (FPA), 11 dehydro-thromboxane B2 (11-dehydro-TXB2) and red cell deformability (RCD). The following parameters demonstrated significant circadian variation: tPA P less than 0.001, PAI P less than 0.04 and 11-dehydro-TXB2 P less than 0.005 (two-way analysis of variance). tPA was highest at 16.00-20.00 and lowest at 08.00; PAI was highest at 08.00 and lowest at 20.00; TXB2 had a peak at 16.00 and trough at 04.00. As the behaviour of endothelial cells and platelets influence the rheological properties of blood, circadian variations in their behaviour may contribute to the time of onset of thrombotic disorders. PMID- 1932531 TI - In vivo and in vitro effects of low molecular weight heparan sulphate on the human fibrinolytic enzyme system. AB - The aim of this study was to evaluate the effects of a preparation of low molecular weight heparan sulphate (LMW-HS) on the fibrinolytic system. Twenty five healthy volunteers received LMW-HS by mouth in three separate experiments. In the first experiment, 10 volunteers received either 80 mg LMW-HS or placebo in a single-blind cross-over study; blood samples were taken before and 1, 2, 3 and 6 h after treatment. LMW-HS caused an increase in global fibrinolysis, the effect being greatest after 2-3 h and disappearing by 6 h. However, neither plasminogen activator activity nor tissue-type plasminogen activator (tPA) antigen levels were changed. In the second experiment, daily doses of 80 mg LMW-HS were administered to 10 volunteers for 7 days; this regimen did not produce a statistically significant increase in fibrinolytic activity for the whole group although some individuals did respond markedly. In the third experiment, 160 mg LMW-HS administered to five volunteers did not affect ADP- and collagen-induced platelet aggregation. In vitro, LMW-HS added to plasma at concentrations of 20 and 30 micrograms/ml, brought about a significant increase in apparent plasminogen activator activity. These results suggest that the increased fibrinolytic activity seen after LMW-HS is due to the recruitment of additional amounts of tPA in the ex vivo test system. LMW-HS had no effect on plasminogen activator inhibitor. PMID- 1932532 TI - The sequence A alpha-(154-159) of fibrinogen is capable of accelerating the t-PA catalysed activation of plasminogen. AB - The rate of activation of plasminogen by tissue-type plasminogen activator (t-PA) is greatly increased by fibrin, but much less by fibrinogen. Fibrin(ogen) fragments such as the fibrin(ogen) cyanogen bromide fragment FCB-2 and FCB-5, and a synthetic peptide with the sequence of fibrinogen A alpha-(148-160), a constituent of FCB-2, also have rate-enhancing properties. In order to find a possibly smaller, still stimulating site within A alpha-(148-160) we synthesized successive linear amino-terminally acylated hexapeptides [i.e. A alpha-(148-153), A alpha-(149-154)'d, .... A alpha-(155-160)] from the sequence A alpha-(148-160). The only hexapeptide within the sequence A alpha-(148-160) capable of enhancing the rate of plasminogen-to-plasmin conversion by t-PA appears to be the amino terminally acylated peptide comprising the sequence A alpha-(154-159). This peptide enhances the plasminogen activation rate six-fold; half-maximal activation rate is reached at a peptide concentration of 56 microM. PMID- 1932533 TI - Aortic aneurysms and consumptive coagulopathy. AB - We describe three cases of consumptive coagulopathy caused by extensive thrombus formation in otherwise 'uncomplicated' aortic aneurysms. These cases demonstrate the importance of performing a coagulation screen in any patient presenting with thrombocytopenia who may have an aortic aneurysm. Effective therapy with low-dose heparin was demonstrated with subsequent haemostasis being maintained with warfarin. PMID- 1932534 TI - [The oculomotor system--simulation of physiologic and pathologic horizontal saccadic eye movements]. AB - Horizontal saccadic eye movements were analyzed by way of the input- and output functions of the oculomotor system. On the basis of the parameters of the model, it was possible to simulate both physiological and pathological saccades. In this paper we present the results of simulation experiments that were performed to study the influence of various ocular motor disorders. The parameters of the model proved a useful diagnostic aid. PMID- 1932535 TI - [Al-assisted, transputer based EMG system--concept, components and initial results]. AB - An EMG system has been developed capable of doing an EMG analysis as well as providing diagnostic support with the aid of an integrated expert system. The goal of this EMG system is to reduce the time of examination and to increase the reliability of the diagnosis. In order to obtain many parameters from the EMG signal, different analysing methods capable of running in parallel are needed. The system has been realized with a transputer network. Thus it is possible to distribute the software components to different processors with high level of efficiency. For software development we use the operating system Helios. This makes it possible to use the standard I/O environment X-Windows. PMID- 1932536 TI - [Thermal knot fixation]. AB - Knots represent the weakest point in suture material. As a result of bending and tension, forces develop within the knot that exceed the strength of the suture material and lead to rupture. Furthermore, because of their relatively large surface area, the most pronounced reactions occur in the vicinity of knots. The results of in vitro experiments conducted with the aim of improving the strength of knots are reported. The knot holding capacity of polypropylene filaments (EP 5/USP 2) was determined at room temperature (22 degrees C) after exposure to temperatures of 63, 98 and 150 degrees C. Knots that were exposed to a temperature of 98 degrees C for 10 seconds had a 50% higher holding capacity than untreated knots. With a higher knot holding capacity, secure fixation can be achieved with fewer knots. Since fewer knots have a smaller surface area, a reduction in tissue reaction may be expected. PMID- 1932537 TI - [A simple setup for measuring scattering in testing the photodynamic effectiveness of dyes]. AB - An experimental setup for the determination of the photodynamic activity of dyes on the basis of scattering measurements is described. With its aid, photochemically induced morphological changes and the process of cell lysis can be registered, and action spectra measured by varying the irradiation wavelength. Different photoproducts of the photosensitizer hematoporphyrin derivative (HPD) were tested in human erythrocyte suspensions. The photodynamic activity of these products was found to depend on absorption behavior, but is lower than that of HPD. PMID- 1932538 TI - [Electrochemical measuring system for the registration of transmucosal gastrointestinal potential differences]. AB - An electrochemical measuring system for the recording of transmucosal gastrointestinal potential differences based on silver electrodes with double junctions and continuous-flow saline bridges is described. Under bioelectrochemical control, a probe can passed from the esophagus via the stomach into the duodenum can be accurately assigned to each of these three segments of the intestine. Measurements are demonstrated and applications discussed. PMID- 1932539 TI - [The rating box--a new instrument for ambulatory detection of subjective variables]. AB - For the acquisition of subjective variables in outpatients and inpatients, a new device--the Rating Box--has been designed. The Rating Box provides a standardized, date- and time-logged documentation of symptoms by the patient and rapid transfer of data to a personal computer. The simultaneous acquisition of several symptoms using different types of scales is possible. The acoustic alarm of the Rating Box reminds the patient to enter data at preselected times. The device is easy to handle, even by older patients, and has been successfully tested in the acquisition of pain variables in patients with a variety of painful conditions. PMID- 1932540 TI - [Electrochemical evaluation of (Ti, Nb) ON-coated dental alloys for quality assurance]. AB - The chemically stable (Ti, Nb) ON hard coating is suitable for passivating the 18 dental alloys investigated. The exchange current densities are less than jg = 1 microA/cm2. The corrosion current densities are included in this, and are therefore generally lower. The electrochemical investigations provide no hints as to local corrosion for (Ti, Nb) ON-coated dental alloys, which could be a hazard for patients or for dental work, owing to galvanic corrosion or pitting on long term use. Irrespective of the coated dental alloy, the coatings have pores, through which the electrolyte is in contact with the substrate material. The resulting local elements have high source resistances, so that with a relative pore-area not exceeding 2% only low galvanic current densities occur. PMID- 1932541 TI - Nutrients and pancreatic cancer: a population-based case-control study. AB - A case-control study was conducted in the Minneapolis-St Paul (Minnesota, United States) area to assess the role of dietary factors in the etiology of pancreatic cancer. Cases were White males aged 40 to 84 whose death certificate listed pancreatic cancer (exocrine only). White male controls were ascertained through random-digit dialing. Family members were interviewed about the subject's dietary usage in the two years prior to death (cases, n = 212) or prior to interview (controls, n = 220). Energy-adjusted, nutrient-intake, risk estimates were calculated. Among all respondents, negative trends were observed for polyunsaturated fat, linoleic acid, vitamin C, and beta-carotene. Positive trends were observed for riboflavin and retinol. Point estimates were, in general, comparable between the analyses of all respondents and spouse-only respondents. The nutrients associated with a decreased risk for pancreatic cancer occur primarily in vegetables and fruits, of which the consumption of cruciferous and beta-carotene-rich vegetables and citrus fruits provided the greatest reduction in risk. PMID- 1932542 TI - Temporal trends in the incidence of cutaneous malignant melanoma among Caucasians in the San Francisco-Oakland MSA. AB - Temporal changes in the incidence of cutaneous malignant melanoma (CMM) were examined in the San Francisco-Oakland (California, United States) Metropolitan Statistical Area (MSA) between 1976 and 1987, using data from the population based cancer registry. This analysis was conducted after the completion of a project designed to eliminate bias in the reporting of CMM due to changes in medical practice. The incidence of CMM is higher in the San Francisco-Oakland MSA than nationally. From 1976 through 1987, the incidence of invasive CMM increased from 9.8 +/- 0.9 to 16.5 +/- 1.1 per 100,000 (P = 0.0001) among men and from 9.3 +/- 0.8 to 12.7 +/- 0.9 per 100,000 (P = 0.001) among women. Age-specific, histologic-specific, and anatomic site-specific trends were also evaluated. The temporal patterns of CMM suggest that the recent increases are not accounted for solely by ascertainment bias due to reporting practices. The observed trends are consistent with early detection efforts and with changes in the prevalence of risk factors. PMID- 1932543 TI - Cancer risk in patients with diabetes mellitus. AB - Cancer incidence was ascertained in a population-based cohort of 51,008 patients in Uppsala, Sweden, who were given a discharge diagnosis of diabetes mellitus during 1965-83. Complete follow-up through 1984 with exclusion of the first year of observation showed that the observed number of cancers in females (1,294) was eight percent higher than expected (relative risk [RR] = 1.1, 95 percent confidence interval = 1.0-1.1), whereas in males the observed number (1,123) was close to the expected (RR = 1.0, 0.9-1.1). Significantly increased risks of pancreatic (RR = 1.4, 1.2-1.7), primary liver (RR = 1.5, 1.2-1.7), and endometrial (RR = 1.5, 1.2-1.8) cancers and a lower than expected number of prostatic cancers (RR = 0.7, 0.7-0.9) were found in this cohort of diabetic patients. The excess risk of pancreatic cancer was similar in females and males and evident both during one through four years (RR = 1.7, 1.4-2.1) and five through nine years (RR = 1.3, 0.9-1.7) of follow-up, but not thereafter. A similar pattern was found for primary liver cancer, but the RRs were generally higher in males than in females. PMID- 1932545 TI - Ion gradient-induced membrane translocation of model peptides. AB - The K+ diffusion potential-induced association of synthetic model peptides carrying a single positive charge originating from the NH2-terminal amino function with large unilamellar vesicles (LUV) consisting of phosphatidylcholine (PC) has been reported previously (de Kroon, A. I. P. M., J. de Gier, and B. de Kruijff. 1989. Biochim. Biophys. Acta. 981:371-373). To determine the vesicle localization of the associated peptides, fluorescence measurements utilizing the peptides' tryptophan residue as intrinsic fluorescent probe were performed. The application in these measurements, of vesicles that exhibit an asymmetric transbilayer distribution of brominated PC which is a quencher of tryptophan fluorescence, unequivocally demonstrated that the peptide H3N(+)-AIMLWA-Ome (AIXme+) is accumulated in the interface of the inner leaflet of the vesicle membrane in response to the valinomycin-induced K+ diffusion potential (negative inside). The relative contributions of the membrane potential (delta psi) and the pH gradient (delta pH, acidic inside) induced by the K+ diffusion potential, to the process have been assessed. An analysis of the pH and delta pH dependencies of the process demonstrated that the K+ diffusion potential-induced peptide accumulation is largely determined by a redistribution of peptide according to the transbilayer pH gradient, in agreement with a translocation across the vesicle membrane of the neutral, deprotonated form of the peptide. The general validity of the mechanism proposed for the vesicle-uptake of AIXme+ has been examined by extending the experiments to peptide analogues with a single negative charge and to peptides with two positive charges, and by investigating the effect of incorporating the acidic phospholipid cardiolipin (CL) into the LUV. The incorporation of CL appeared not to affect the K+ diffusion, potential-induced vesicle uptake of AIXme+. The peptide H3N(+)-RMLWA-Ome (RXme2+) showed a small delta pH independent fluorescence response to the delta psi upon raising the CL content of the vesicles to 25%. PMID- 1932544 TI - Incidence of childhood cancer in twins. AB - The incidence of childhood cancer in twins was evaluated by linking a roster of 30,925 twins born in Connecticut (United States) between 1930 and 1969 with the Connecticut Tumor Registry. Cancer, exclusive of nonmelanoma skin cancer, was identified in 19 females and 12 males under 15 years of age. The incidence rate among twins was 7.9 cancers per 100,000 person-years (PY) overall, and 9.7 and 6.1 per 100,000 PYs for females and males, respectively. Four of 13 leukemias occurred in two female twin pairs, representing concordance rates of 18 percent overall and 29 percent for like-sex pairs, which are somewhat higher than values reported previously. The number of cancers expected was computed on the assumption that twins experienced the same sex-, age-, and calendar time-specific cancer rates as recorded for all Connecticut-born children. Because active follow up of individuals was not conducted, an adjustment to person-years of observation was made to account for childhood mortality, including the high perinatal mortality characteristic of twins. Childhood cancer was 30 percent less frequent than expected (standardized incidence ratio [SIR] = 0.7; 95 percent confidence interval [CI] = 0.5-0.9), a deficit that is marginally greater than those found in previous studies. Both leukemia (SIR = 0.8; CI = 0.4-1.4), and all other cancers combined (SIR = 0.6; CI = 0.3-0.9) occurred less often than expected. The deficit was greater among males (SIR = 0.5; CI = 0.2-0.8) than among females (SIR = 0.9; CI = 0.5-1.4) and was especially pronounced among males younger than five years (SIR = 0.2; CI = 0.0-0.7). The data support the view that twins, particularly male twins, have a lower risk of childhood cancer than single-born children. Any added risk for twins associated with their greater frequency of exposure to prenatal X-rays appears to have been insufficient to offset an 'effect' of twinning per se. Possible explanations for this finding include (i) the low birthweight distribution of twins, or (ii) selective early mortality of twin fetuses or neonates who would otherwise have developed a clinical cancer. PMID- 1932546 TI - Analytical theory for extracellular electrical stimulation of nerve with focal electrodes. II. Passive myelinated axon. AB - The cable model of a passive, myelinated fiber is derived using the theory of electromagnetic propagation in periodic structures. The cable may be excited by an intracellular source or by an arbitrary, time-varying, applied extracellular field. When the cable is stimulated by a distant source, its properties are qualitatively similar to an unmyelinated fiber. Under these conditions relative threshold is proportional to the cube of the source distance and inversely proportional to the square of the fiber diameter. Electrical parameters of the model are chosen where possible, from mammalian peripheral nerve and anatomic parameters from cat auditory nerve. Several anatomic representations of the paranodal region are analyzed for their effects on the length and time constants of the fibers. Sensitivity of the model to parameter changes is studied. The linear model reliably predicts the effects of fiber size and electrode-fiber separation on threshold of cat dorsal column fibers to extracellular electrical stimulation. PMID- 1932547 TI - The propagation potential. An axonal response with implications for scalp recorded EEG. AB - An electrophysiological response of axons, referred to as the "propagation potential," was investigated. The propagation potential is a sustained voltage that lasts as long as an action potential propagates between two widely spaced electrodes. The sign of the potential depends on the direction of action potential propagation. The electrode towards which the action potential is propagating is positive with respect to the electrode from which it is receding. For normal frog sciatic nerves the magnitude of the propagation potential was 17% of the peak of the extracellular action potential; TEA increased it to 32%. For normal earthworm median or lateral giant fibers it was 30%. A ripple pattern on the propagation potential was attributed to variation in resistance along the length of the worm. Cooling increased the duration of the propagation potential and attenuated the higher frequency components of the ripple pattern. Differential records from two widely spaced intracellular microelectrodes in the same axon differed from the propagation potential. The amplitude of the plateau relative to the peak was smaller, it decreased as the action potential propagated from one electrode site to the other, and the potential did not return to zero as rapidly as for extracellular records. When propagation was blocked by heat, the propagation potential slowly decayed. There was no ripple pattern during the decay. In a volume conductor, electrodes contacting the worm did not show the typical propagation potential, but electrodes located a few centimeters away from the worm did. Simple core-conductor models based on classical action potential theory did not reproduce the propagation potential. More complex, modified core conductor models were needed to accurately simulate it. The results suggest that long, slowly conducting fibers can contribute to the scalp-recorded EEG. PMID- 1932548 TI - Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. I. Scaling of neutron data and the distributions of double bonds and water. AB - We described in two previous papers a method for the joint refinement of the structure of fluid bilayers using neutron and x-ray diffraction data (Wiener, M. C., and S. H. White 1991a, b. Biophys. J. 59: 162-173 and 174-185). An essential part of the method is the appropriate scaling of the diffraction data. Here we describe the scaling of the neutron data and the determination of the transbilayer distribution of double bonds in liquid-crystalline (L alpha phase) phospholipid bilayers of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The distribution was determined by neutron diffraction of oriented multilayers (66% RH) of DOPC specifically deuterated at the 9- and 10-position of both acyl chains. The double-bond distribution is described accurately by a pair of Gaussian functions each located at a position Zcc = 7.88 +/- 0.09 A from the bilayer center with 1/e-halfwidths of Acc = 4.29 +/- 0.16 A. Previously, we determined the transbilayer distribution of bromine atoms in a specifically halogenated lipid, 1-oleoyl-2-9,10-dibromostearoyl-sn-glycero-3-phosphocholine (OBPC), and showed it to be an isomorphous replacement for DOPC (Wiener, M. C., and S. H. White, 1991c. Biochemistry. In press). A comparison of the double-bond and bromine profiles indicates that the positions of the centers of the deuterated double bond and the brominated methylene Gaussian distributions are equal within experimental error and that each label undergoes similar average thermal motions with respect to the bilayer normal. The observation that the average position of a label on both acyl chains (the deuterated double bonds) is similar to the average position of a label on the 2-chain alone (the brominated methylenes) indicates that the maximum separation along the bilayer normal between the double bonds of the acyl chains is 1 A or less. The fully-resolved transbilayer water distribution, previously determined at lower resolution (Jacobs, R. E., and S. H. White. 1989. Biochemistry. 28:3421-3437), was obtained from the analysis of neutron diffraction data of DOPC hydrated with a D20/H20 mixture. The water distribution is described accurately by a pair of Gaussian functions each located at a position Zw = 22.51 +/- 0.77 A from the bilayer center with 1/e-half widths of Aw = 4.63 +/- 0.48A. We present the relative absolute neutron and x-ray structure factors of DOPC at 66% RH that will be used to solve the complete structure of DOPC which will be presented in a later paper of this series. PMID- 1932549 TI - Altered electrophysiologic and pharmacologic response of smooth muscle cells on exposure to electrical fields generated by blood flow. AB - The flow of the blood past the vascular wall gives rise to an electrical potential. This field is calculated to have a periodic waveform with a transluminal peak-to-peak amplitude of approximately 1.35 V/m-1. Digital imaging fluorescent microscopy was used to measure changes in the membrane potentials of smooth muscle cells by following changes in the fluorescence of the potential sensitive dye, 3,3'-dipropyloxacarbocyanine iodide (di-O-C5[3]). The effect of the low level electrical field on the membrane potentials of cultured smooth muscle vascular cells was shown to cause a steady-state depolarization of approximately 10 mV. The degree of steady-state depolarization was shown to directly vary with the frequency of the applied field and the effect was not dependent on the presence of extracellular Ca+2 or Mg+2. These effects are though to be most consistent with an electroconformational coupling mechanism. The presence of this electrokinetic field was also shown to alter the electrophysiological response of smooth muscle cells treated with 5 hydroxytryptamine. Cells exposed concurrently to both 5-HT and the electrical field showed an increased membrane depolarization thus implying that the electrokinetic field may be important in both normal and pathologic cellular responses. PMID- 1932550 TI - Measurement of mass transport and reaction parameters in bulk solution using photobleaching. Reaction limited binding regime. AB - Fluorescence recovery after photobleaching (FRAP) has been used previously to investigate the kinetics of binding to biological surfaces. The present study adapts and further develops this technique for the quantification of mass transport and reaction parameters in bulk media. The technique's ability to obtain the bulk diffusion coefficient, concentration of binding sites, and equilibrium binding constant for ligand/receptor interactions in the reaction limited binding regime is assessed using the B72.3/TAG-72 monoclonal antibody/tumor associated antigen interaction as a model in vitro system. Measurements were independently verified using fluorometry. The bulk diffusion coefficient, concentration of binding sites and equilibrium binding constant for the system investigated were 6.1 +/- 1.1 x 10(-7) cm2/s, 4.4 +/- 0.6 x 10(-7) M, and 2.5 +/- 1.6 x 10(7) M-1, respectively. Model robustness and the applicability of the technique for in vivo quantification of mass transport and reaction parameters are addressed. With a suitable animal model, it is believed that this technique is capable of quantifying mass transport and reaction parameters in vivo. PMID- 1932551 TI - Mass-weighted molecular dynamics simulation and conformational analysis of polypeptide. AB - Atomic motions in protein molecules have been studied by molecular dynamics (MD) simulations; dynamics simulation methods have also been employed in conformational studies of polypeptide molecules. It was found that when atomic masses are weighted, the molecular dynamics method can significantly increase the sampling of dihedral conformation space in such studies, compared to a conventional MD simulation of the same total simulation time length. Herein the theoretical study of molecular conformation sampling by the molecular dynamics based simulation method in which atomic masses are weighted is reported in detail; moreover, a numerical scheme for analyzing the extensive conformational sampling in the simulation of a tetrapeptide amide molecule is presented. From numerical analyses of the mass-weighted molecular dynamics trajectories of backbone dihedral angles, low-resolution structures covering the entire backbone dihedral conformation space of the molecule were determined, and the distribution of rotationally stable conformations in this space were analyzed quantitatively. The theoretical analyses based on the computer simulation and numerical analytical methods suggest that distinctive regimes in the conformational space of the peptide molecule can be identified. PMID- 1932552 TI - Analysis of edge birefringence. AB - We present an experimental and theoretical study of the phenomenon of edge birefringence that appears near boundaries of transparent objects which are observed with high extinction and high resolution polarized light microscopy. As test objects, thin flakes of isotropic KCl crystals were immersed in media of various refractive indices. The measured retardation near crystal edges increased linearly with both the crystal thickness (tested between 0.3 and 1 micron), and the difference in refractive indices n between crystal (n = 1.49) and immersion liquids (n between 1.36 and 1.62). The specific edge birefringence, i.e., the retardation per thickness and per refractive index difference, is 0.029 on the high refractive index side of the boundary and -0.015 on the low refractive index side. The transition through zero birefringence specifies the position of a boundary at a much higher precision than predicted by the diffraction limit of the optical setup. The theoretical study employs a ray tracing procedure modeling the change in phase and polarization of rays passing through the specimen. We find good agreement between the model calculations and the experimental results indicating that edge birefringence can be attributed to the change in polarization of light that is refracted and reflected by dielectric interfaces. PMID- 1932553 TI - Resolution of fluorescence intensity decays of the two tryptophan residues in glutamine-binding protein from Escherichia coli using single tryptophan mutants. AB - Time correlated single photon counting measurements of tryptophan (Trp) fluorescence intensity decay and other spectroscopic studies were performed on glutamine-binding protein (GlnBP) from Escherichia coli. Using site-specifically mutated forms of the protein in which tyrosine (Tyr) and phenylalanine (Phe) substitute for the Trp residues at positions 32 and 220, we have examined whether wild-type (Wtyp) intensity decay components may be assigned to specific Trp residues. Results indicate that: (a) two exponential intensity decay components are recovered from the Wtyp protein (6.16 ns, 0.46 ns); (b) the long decay component arises from Trp-220 and comprises greater than 90% of the total fluorescence emission; (c) the short component arises from Trp-32 and is highly quenched; (d) all four single-Trp mutants exhibit multiexponential intensity decays, yet equimolar mixtures of two single-Trp mutants yield only two decay components which are virtually indistinguishable from the Wtyp protein; (e) the recovery of additional components in protein mixtures is obscured by statistical noise inherent in the technique of photon counting; (f) various spectroscopic measurements suggest that Trp-Trp interactions occur in the Wtyp protein, but the Wtyp intensity decay may be closely approximated by a linear combination of intensity decays from single-Trp mutants; and (g) inferences derived independently from fluorescence and NMR spectroscopy which pertain to the presence of Trp-Trp interactions and the relative solvent exposure of the two Trp residues are in agreement. PMID- 1932554 TI - Equilibrium muscle cross-bridge behavior. Theoretical considerations. II. Model describing the behavior of strongly-binding cross-bridges when both heads of myosin bind to the actin filament. AB - A model has been developed for characterizing the interaction between strongly binding myosin cross-bridges and actin in muscle fibers under equilibrium conditions where both heads of the myosin cross-bridge bind to actin. The model, that of Anderson and Schoenberg (1987. Biophys. J. 52:1077-1082) is quite similar to that of Schoenberg (1985. Biophys. J. 48:467-475), except that explicit account is taken of the fact that each crossbridge has two heads which can bind to actin. The key assumption that allows this model to explain a large body of data unexplained by the Schoenberg (1985) model is that the two crossbridge heads are not totally independent of one another after attachment. After the first head attaches, the second head is then free to attach only to an actin site distal to the first head. This means that when the more distally attached head subsequently detaches and reattaches (as the heads continually do), it will not reattach in a position of lesser strain and reduce the force it supports, but instead will remain attached in its strained position until the proximally attached head also detaches. This model gives an explanation for two important and otherwise unexplained observations made previously: it explains why at ionic strengths in the range of 50-120 mM, (a) the rate constant of force decay after a small stretch is a sigmoidal function of nucleotide analogue concentration, and (b) why in the presence of analogues or in rigor the rate constant of force decay after a small stretch is significantly slower than the rate constant for myosin subfragment-1 detachment from actin in solution. PMID- 1932555 TI - Reversible deformation-dependent erythrocyte cation leak. Extreme sensitivity conferred by minimal peroxidation. AB - To determine the threshold at which red blood cells (RBC) begin to manifest deformation-dependent leakiness to monovalent cations, we examined net passive potassium leak during elliptical deformation. Normal RBC did not begin to leak appreciable amounts of potassium until shear stress reached 204 dyn/cm2, at which point they had attained greater than 96% of their maximal deformation. In striking contrast, RBC that had undergone minimal, physiologically relevant degrees of peroxidative damage induced by t-butylhydroperoxide began to leak potassium at only 59 dyn/cm2 when they had reached only 63% of their maximal deformation. The cation leak identified in this manner is not prelytic, and it is fully reversible. Therefore, these data may be relevant to abnormal cation leaks that develop in sickle red cells that have membranes damaged by auto-oxidative stress and that manifest an exuberant but reversible leakiness to monovalent cation during sickling-induced deformation of the cell membrane. PMID- 1932556 TI - Effect of bile salts on monolayer curvature of a phosphatidylethanolamine/water model membrane system. AB - A partial phase diagram of the ternary system dioleoylphosphatidylethanolamine (DOPE)/sodium cholate/water has been determined using 31P Nuclear Magnetic Resonance (NMR) spectroscopy. In the absence of cholate, it is well known that the DOPE/water system forms a reversed hexagonal (HII) phase. We have found that addition of even small amounts of cholate to the DOPE/water system leads to a transition to a lamellar (L alpha) phase. At higher cholate concentrations, a cubic (I) phase (low water content) or a micellar solution (L1) phase (high water content) is present. Thus, cholate molecules have a strong tendency to alter the lipid monolayer curvature. Increasing the concentration of cholate changes the curvature of DOPE from negative (HII phase), through zero (L alpha phase), and finally to a phase of positive curvature (micellar solution). This observation can be rationalized in terms of the molecular structure of cholate, which is amphipathic and has one hydrophobic and one hydrophilic side of the steroid ring system. The cholate molecules have a tendency to lie flat on the lipid aggregate surface, thereby increasing the effective interfacial area of the polar head groups, and altering the curvature free energy of the system. PMID- 1932557 TI - Membrane fluctuations in erythrocytes are linked to MgATP-dependent dynamic assembly of the membrane skeleton. AB - The observation of low-frequency fluctuations of the cell membrane in erythrocytes and in several nucleated cells suggests that this phenomenon may be a general property of the living cell. A study of these fluctuations in human erythrocytes and its ghosts has now been carried out using a novel optical method based on point dark field microscopy. We have demonstrated that the reestablishment of membrane fluctuations in erythrocyte ghosts is dependent on MgATP but does not necessarily require the restoration of the biconcave shape. The results imply that the dominant component of membrane fluctuations are metabolically dependent and suggest the existence of a dynamic mechano-chemical coupling within the membrane skeleton network induced by MgATP. PMID- 1932558 TI - Comments on direct visualization of protein complexes by scanning tunneling microscopy. PMID- 1932559 TI - Toward the elucidation of the mechanism of attachment and entry of malaria sporozoites into cells: synthetic polypeptides from the circumsporozoite protein of Plasmodium falciparum bind Ca2+ and interact with model phospholipid membranes. AB - Through the joint use of CD, Fourier transform ir (FTIR), and attenuated total reflectance FTIR we have found that synthetic polypeptide models of the Plasmodium falciparum circumsporozoite (CS) protein repeat domain bind calcium ions in helicogenic environments. Ca(2+)-(NANP)n complexes (n greater than or equal to 20) interact vectorially with model phospholipid membranes orienting their polypeptide axes preferentially along those of the lipid acyl chains. It is proposed that the P. falciparum CS protein central region, rather than acting as a molecular lure helping the parasite to evade host immune control, plays, as a specific Ca2+ macroligand, a critical functional role during attachment, invasion, and development of the malaria parasite in the hepatic cell. PMID- 1932560 TI - Synthetic immunogens. Part IV: Conformational studies on gastrin conjugates with the human immunoglobulin G1 hinge peptide 225-232/225'-232'. AB - Hybrids of the double-chain bis-cystinyl fragment 225-232/225'-232' of human immunoglobulin G1 (IgG1) with the human little-gastrin sequence 2-17 were found to induce in animals a strong antigastrin humoral immune response with antibody titers comparable to those raised with conventional gastrin/carrier-protein conjugates. The observed gastrin receptor-like specificity of the polyclonal antibodies led to the assumption that the gastrin component of the hybrids is still capable of folding into its preferred bioactive structure and thus to express a similar conformational epitope in the dynamic process of recognition by the B-cell receptors. CD measurements on these hybrid compounds in aqueous and aqueous organic media confirmed the free conformational space for the antigenic gastrin moiety, which is essentially randomly coiled in aqueous solution but retains its ability to fold into the gastrin-specific ordered structure in aqueous organic media as used to mimic the water-limited environment of peptides while interacting with target cells at receptor level. The absence of reciprocal conformational restriction in such hybrid molecules suggests that a compact, rigid heterodetic cyclic structure as the hinge peptide is well suited for the multiple attachment of antigenic sequences in view of the preparation of fully synthetic immunogens. PMID- 1932561 TI - Conformational analysis of bacitracin A, a naturally occurring lariat. AB - The proton nmr spectra of bacitracin A in H2O and DMSO-d6 have been assigned and the conformational behavior of the peptide in the two solvents has been compared. Although bacitracin A shows a conformational equilibrium between at least two conformations differing in the relative position of the cyclic and linear domains of the molecule, the spectra in water can be interpreted in terms of a preferred conformation in which the linear part is folded over the cyclic moiety and a turn is present around Ile(8)-DPhe(9). PMID- 1932562 TI - Structure and antigenic activity of rubella E1 glycoprotein synthetic peptides. AB - Minimal sequences of rubella E1 glycoprotein epitopes were previously identified as the tripeptide 250PER252 for the EP2 epitope, the tetrapeptide 260ADDP263 for the EP3 epitope, and the tripeptide 273EVW275 plus the octapeptide 278PVIGSQAR285 for the EP1 epitope. In order to establish for each epitope the shortest sequence that was able to give the maximum binding with human antirubella immunoglobulins, synthetic peptides with increasing number of residues flanking these essential parts of rubella E1 glycoprotein epitopes were synthesized and examined for their antigenic activity. Usually higher activity was observed with progressively longer homologues, whereas the additions of Pro-271, Pro-278 to 272GEVWVT277 peptide, and additions of Ala-248 to 249TPERP253 and 249TPERPR254, led to an abrupt decrease in binding. Taken together, our results indicated that the antigenic activity of the whole antigen could be dissected and reproduced using synthetic peptides of appropriate structure for each epitope. PMID- 1932563 TI - Preferred conformation of peptides from C alpha,alpha- symmetrically disubstituted glycines: aromatic residues. AB - The conformational preference of C(alpha,alpha-diphenylglycine (D-phi-g) and C(alpha,alpha)-dibenzylglycine (Dbz) residues was assessed in selected derivatives and small peptides by conformational energy computations, ir absorption, 1H-nmr, and x-ray diffraction. Conformational energy computations on the two monopeptides strongly support the view that these C(alpha,alpha) symmetrically disubstituted glycines are conformationally restricted and that their minimum energy conformation falls in the fully extended (C5) region. The results of the theoretical analyses appear to be in agreement with the solution and crystal-state structural propensities of three derivatives and seven di- and tripeptides. PMID- 1932564 TI - Fluorescence and CD studies on the conformation of the gastrin releasing peptide in solution and in the presence of model membranes. AB - The conformation of the heptacosapeptide hormone, gastrin releasing peptide, has been studied in buffer and in the presence of lipids, using static and dynamic fluorescence and CD. The results obtained show that, in buffer, the hormone exists in a collection of flexible, random coil type conformers, characterized by a beta-turn between residues 14-19. On the other hand, organic solvents can induce some degree of ordered secondary structure in the peptide chain. The marked changes, observed in CD and fluorescence spectra upon addition of lysolecitin micelles and dimyristoylphosphatidylserine vesicles, clearly show that the peptide interacts with lipids, assuming a lipid specific configuration. Interestingly, no significative spectroscopic changes are produced by exposure to dimyristoylphosphatidylcholine vesicles both in the gel and liquid-chrystalline phases, suggesting a requirement for negatively charged lipids during the process of hormone-membrane interaction. PMID- 1932565 TI - Conformational and binding studies on peptides related to domains I and III of calmodulin. AB - The conformational and ion-binding properties of two peptide fragments of 25 amino acid residues corresponding to the helix-loop sequences of domains I and III of calmodulin (CaM) were investigated by CD and Tb(3+)-mediated fluorescence spectroscopy. Both peptides exhibit very similar ion binding properties either in water or trifluoroethanol (TFE), and do not allow the differentiation of the two domains in the native protein in terms of their binding capacity. An aggregation phenomenon was observed in TFE with increase of the alpha-helical content. We suggest that the aggregation involves an interaction between the hydrophilic surfaces of amphiphilic alpha-helices in a way similar to inverse micelle formation. PMID- 1932566 TI - Conformational preferences and the role of the statine residue in the crystal state. AB - The present paper is the result of an analysis of the available crystal structure data related to the statine amino acid so as to obtain information about bond lengths, bond angles, and preferential conformations. The number of configurations actually observed is small; nevertheless, some characteristic conformations should be pointed out for statine-containing peptides. The presence of two additional carbon atoms in the statine main chain enhances the peptide conformational degree of freedom and the statine-containing peptides are observed in a variety of different conformations including some usual secondary structure types as beta-turns and beta-strands. PMID- 1932567 TI - Conformation-based design of two cyclic physalaemin analogues. AB - Two new cyclic analogues of physalaemin were designed on the basis of the conformation found in DMSO solution. Glp-Ala-cyclo(-Asp-Pro-Asn-Lys-)-Phe-Tyr-Gly Leu-Met-NH2 (1) was synthesized by cyclization of physalaemin. In 2 the Asp residue was replaced by Glu. The linear analogue of 2 was synthesized by the solid phase method and subsequently cyclized. Two-dimensional nmr methods were employed to assign the proton and carbon resonances. Proton-proton distances were extracted from rotating frame nuclear Overhauser effect spectra and used as restraints in the molecular dynamics calculations. Analogue 1 was found to have a similar conformation as physalaemin, whereas 2 did not form intramolecular hydrogen bonds. The pharmacological evaluation revealed that both peptides have similar potencies as physalaemin in the dog carotid artery (NK-1 receptor). Therefore, the charged side chains of physalaemin appear not essential for NK-1 activation. However, the other tachykinin receptors show good sensitivity to the cyclic peptides. It is concluded that the replacement of a salt bridge by an amide bond connecting the side chains of natural residues might provide useful information about the biological significance of some charged side chains of neurokinins. PMID- 1932568 TI - Assignment of protein NMR spectra in the light of homonuclear 3D spectroscopy: an automatable procedure based on 3D TOCSY-TOCSY and 3D TOCSY-NOESY. AB - Automated assignment of proteins is greatly simplified using data from 3D-nmr spectra. A strategy is presented which makes use of 3D-TOCSY-TOCSY and 3D-TOCSY NOESY; its potential is demonstrated with the example of the spectra of BPTI. The discussion of the potential of 3D-nmr includes the introduction of a simple graph for the description of the information content of multidimensional nmr spectra. PMID- 1932569 TI - 1H- and natural abundance 15N-NMR studies of a derivative of a rabies glycoprotein fragment. AB - Using a combination of one- and two-dimensional methods, 1H- and 15N-nmr spectroscopy has been employed to perform the complete assignment and the structural determination of the immunogenic undecapeptide CTTTNSRGTTT in DMSO solution. Nuclear Overhauser enhancement spectroscopy experiments indicated the presence of secondary structures, mainly turn-like structures, which only represent a family, albeit a dominant one, of an ensemble of conformations available to the peptide. Since reverse turns may play an important role as intermediates in protein folding, the experimental observations described here may link the immunological and theoretical approaches to protein folding. PMID- 1932570 TI - Conformation and formation tendency of the cyclotetrapeptide cyclo (D-Pro-D-Pro-L Pro-L-Pro): experimental results and molecular modeling studies. AB - The title compound represents the smallest member of cyclic proline peptides corresponding to the general formula c(DDLL-Pro4)n with a strictly D,D,L,L double alternating sequence of the chiral amino acid residues. The cyclopeptides with n greater than or equal to 2 could be synthesized from both DDLL-Pro4 (1) and DLLD Pro4 (2). The cyclic monomer (n = 1) resulted only from 2, whereas not even a trace could be found by cyclization of 1. The peptide exists in a strongly strained Ci symmetrical conformation (x-ray analysis) with alternating cis and trans peptide bonds (ctct form I). The cis peptide bonds deviate from planarity (omega = 22 degrees); two of the pyrrolidine rings show a "South" conformation (phi = -94 degrees), whereas the other residues exhibit C alpha-endo puckering (phi = -124 degrees). Two of the psi angles surprisingly occur at +41 degrees (anti-cis'), the others are located in the trans' region. A quantitative ring opening occurs with trifluoroacetic acid at room temperature. In solution the existence of an isomeric ctcc sequence (form Ia) is indicated. Dreiding model studies also suggested a favorable conformation with a tctc sequence (form II). Consequently, we performed molecular mechanics calculations, based on the CHARMM force field and semiempirical quantum mechanical AM1 calculations (MOPAC program). Pronounced differences in the backbone parameters were found using these two methods. However, the theoretical studies evidenced the experimentally obtained differences in the cyclization tendencies of the linear precursors. PMID- 1932571 TI - New insights on mu/delta selectivity of opioid peptides: conformational analysis of deltorphin analogues. AB - The message domain of dermorphin (Tyr-D-Ala-Phe), a natural mu-opioid heptapeptide, has long been considered the main cause of the high mu selectivity of this peptide and of its analogues. The recent discovery, in the skin of Phyllomedusa sauvagei (i.e., the same natural source of dermorphin) and of Phyllomedusa bicolor of deltorphins, challenges this belief. Deltorphins, in fact, are three heptapeptides characterized by a message domain typical of mu selective peptides, but endowed of an extremely high delta selectivity, the highest of all natural opioid peptides. A conformational analysis of dermorphin and deltorphins, based on nmr studies in DMSO and cryoprotective mixtures and internal energy calculations, showed that the enormous differences in receptor selectivity can be interpreted on the basis of receptor models for mu and delta opioids that recognize the same beta-turn in the N-terminal part, but discriminate for the conformation and polarity of the C-terminal part. Here we present the synthesis, biological activity, and conformational analysis in solution of three deltorphin analogues with very similar constitution, but with different net charge, different location of negative residues, or even without negative residues, which confirm these hypotheses and show that His4 can play a specific structural role. PMID- 1932572 TI - Ion binding of cyclolinopeptide A: an NMR and CD conformational study. AB - CD and nmr techniques have been used to study, in acetonitrile solution, the ion complexing capability of cyclolinopeptide A (CLA), a cyclic nonapeptide of sequence cyclo-(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val) endowed with remarkable cytoprotective ability in vitro, and the conformation of the Ba(2+)/CLA complex. At room temperature, CLA in acetonitrile shows a proton nmr spectrum characteristic of the coexistence of many different conformers in intermediate exchange. The backbone contains a cis Pro-Pro bond, with all other peptide bonds in the trans conformation. CLA binds Ba2+ more tightly than the other cations studied, namely K+, Na+, Mg2+, and Ca2+; CD data are indicative of the presence of both 1:2 (sandwich) and 1:1 (equimolar) type complexes, depending on the Ba2+ ion concentration, whereas nmr data are consistent with an equimolar form. The relevant conformational features of the equimolar Ba2+/CLA complex are that the backbone contains all trans peptide bonds, a type I 6----3 beta-turn and a 3----1 gamma-turn (or a distorted 3----9 beta-turn). The global shape of the complexed peptide can be described as a bowl, with the concave (polar) side hosting Ba2+ and the convex side predominantly apolar. PMID- 1932573 TI - Two-dimensional 1H-NMR study of antigen-antibody interactions: binding of synthetic decapeptides to an anti-acetylcholine receptor monoclonal antibody. AB - Two-dimensional NMR experiments [correlated spectroscopy (COSY) and two dimensional transferred nuclear Overhauser enhancement spectroscopy (TR-NOESY)] have been applied to study the interactions of a monoclonal antibody (mAb) directed to the main immunogenic region (MIR) of the acetylcholine receptor (AChR), and four synthetic decapeptides from the MIR. The decapeptides were the Torpedo AChR alpha 67-76 fragment (W67-N68-P69-A70-D71-Y72-G73-+ ++G74-I75-K76) and its three [A69], [A73], and [A76] analogues. The results led to the following conclusions: (1) the magnitude of the TR-NOE cross peaks does not depend only on the structuration of the peptide in the bound state, but also on restrictions of the mobility, i.e., on the correlation time tau c, which can be different for every residue; (2) the binding capacity of the synthetic peptides to mAbs measured by radioimmunoassay is directly correlated to the NOE magnitude; and (3) the combined interpretation of the COSY and TR-NOESY experiments gives a qualitative information about the nature and the overall conformation of the sequence which is in contact with the mAb binding site. PMID- 1932574 TI - X-ray conformational study of hydrazino peptide analogues. AB - We have solved the crystal structures of nine pseudo-peptide analogues deriving from the hydrazino analogue of glycine or valine (N beta H2-N alpha H-C alpha HR CO2H, R = H or iPr) or proline (N beta H2-N alpha-C alpha H-CO2H) and containing the hydrazide (CO-N beta H-N alpha less than) or N beta-Z-aminoamide [formula; see text] [CO-N alpha(N beta HZ)] peptidomimetic link. This study gives access to the average geometry of these two links, to their inter- and intramolecular interaction modes, and to their influence on the conformational properties of the molecules. PMID- 1932575 TI - The solution structure of the lantibiotic gallidermin. AB - The 21-peptide amide antibiotic gallidermin is a potential therapeutic against acne disease. It belongs to the class of polycyclic lanthionine and alpha,beta didehydroamino acids containing polypeptides, which were named "lantibiotics." The structural gene of the recently elucidated lantibiotic gallidermin encodes a precursor peptide containing Ser, Thr, and Cys residues in the C-terminal prolantibiotic part, and an unusually hydrophilic leader peptide. The ribosomally synthesized pregallidermin is posttranslationally modified and processed to a complex peptide antibiotic with four sulfide rings and two unsaturated residues. The complete solution structure of gallidermin was determined in trifluoroethanol: water (95:5) and dimethylsulfoxide by two-dimensional 1H-nmr at 500 MHz, using a combination of double quantum filtered correlated spectroscopy, homonuclear Hartman-Hahn, and nuclear Overhauser enhancement spectroscopy experiments. Using a total number of 152 distance constraints from NOEs and 14 torsional constraints, derived from coupling constants, we obtained a screwlike solution structure of gallidermin. Restrained molecular dynamics simulations yielded a set of five converging structures with an atomic rms difference of 1.7 A for the backbone atoms, not dependent on the starting structure. The spatial structure model is in excellent agreement with the amphiphilic and channel forming properties of gallidermin on membranes and its tryptic cleavage at the exposed site between residues 13 and 14. PMID- 1932576 TI - Cytopathology of follicular tumours of the thyroid with clear cell change. AB - A retrospective cytological study of nine follicular tumours of the thyroid with clear cell change was undertaken. In five clear cell adenomas and one moderately differentiated clear cell follicular carcinoma the epithelial cells occurred singly or in sheets and clusters; they sometimes assumed a trabecular or follicular pattern. The cells usually had pale diffusely vacuolated cytoplasm with ill-defined boundaries, a variable degree of anisonucleosis, nucleolar enlargement, and nuclear overlapping. Smears from a signet-ring cell adenoma contained in addition a few cells with large cytoplasmic vacuoles and compressed eccentric nuclei. In these cases a cytological diagnosis of 'follicular lesion' (or follicular neoplasia), clear cell type or signet-ring cell type, was given. A cytodiagnosis of 'carcinoma' was made only in the poorly differentiated follicular carcinoma-clear cell variant studied which showed unequivocal features of malignancy. Features suggestive of thyroid cyst, nodular goitre, Hashimoto's thyroiditis, and cell hyperactivity (marginal vacuoles, 'fire flare') were also found in the aspirated specimens of these cases of clear cell tumour of the thyroid. PMID- 1932577 TI - Fine needle aspiration cytology and immunocytochemistry of metastatic melanoma. AB - The cytological and immunological findings of 81 metastatic melanomas are described. Fine needle aspiration was performed from secondary deposits in lymph nodes (38), subcutaneous and soft tissue (36), abdomen (5), lung (1) from 67 patients with histologically verified malignant melanoma. One patient had disease which had spread into the cerebrospinal fluid. Cytomorphologically the cases were classified as classical (47%), carcinoma-like (22%), spindle cell type (14%), lymphoma like (6%), undifferentiated (6%), myxoid type (3%), and clear cell type (2%). All cases were immunologically characterized using antibodies to S-100, vimentin and cytokeratin. All cases were S-100 positive and the majority (96%) reacted with antibodies to vimentin. A weak heterogenous reactivity to cytokeratin antibody was detected in only eight cases. The HMB45 antibody was applied to 20 cases and 16 (80%) of these tumours were positive. In summary, we found that an immunological characterization was necessary to conclusively diagnose over 50% of metastatic melanomas which presented with an equivocal cytological picture. PMID- 1932578 TI - The cytology of Langerhans cell histiocytosis (histiocytosis X). AB - The cytomorphology of 13 cases of Langerhans cell histiocytosis is described. The most striking features were the presence of intranuclear clefts, pale nuclei and inconspicuous nucleoli, together with ample pale cytoplasm, only slight cellular pleomorphism, and an admixture of varying numbers of eosinophils, macrophages and degenerated cells. In 13 of 16 cases investigated ultrastructurally, characteristic Birbeck granules were detected. Out of six cases tested, four exhibited positivity for S-100, and of three cases tested, all were positive for CD1a (leu 6) and HLA-DR. In one case malignant transformation occurred, terminating in monocytic leukaemia. PMID- 1932579 TI - Fine needle aspiration cytology of collagenous spherulosis of the breast. AB - We present a case of a 45-year-old woman with a benign breast lump in which collagenous spherulosis was an incidental finding. Since collagenous spherulosis has a similar appearance to adenoid cystic carcinoma of breast on fine needle aspiration cytology, the two conditions can easily be confused. The problem of making this important distinction is discussed. PMID- 1932580 TI - Two-dimensional crystallization of proteins on lipid monolayers. AB - This review includes details of recent macromolecular crystallizations using lipid monolayers. Crystallization conditions are discussed together with suggestions for improving resolution. PMID- 1932581 TI - The pollen tube cytoskeleton. AB - In the last few years the role of pollen and the pollen tube in the fertilization process in higher plants has received considerable attention. By ultrastructural, biochemical and immunofluorescent investigations it has been shown that a cytoskeletal apparatus plays a central role in pollen tube growth. Microfilaments and microtubules, in which main components are, respectively, actin and tubulin, represent the most investigated cytoskeletal components. New information has been recently provided by the identification of myosin and also of a kinesin-like protein. The pollen tube cytoskeleton consists of two different cytoskeletal systems: the vegetative cell cytoskeleton, namely the cytoskeleton of the pollen grain and pollen tube, and the gamete cytoskeleton (generative cell and sperm cell cytoskeleton). The vegetative cell cytoskeleton plays a fundamental role in assuring the cytoplasmic movement of organelles, vesicles and gametes from the pollen grain to the pollen tube apex and consists mainly of microtubules and microfilaments. Also myosin and the kinesin-like protein are involved in the process of organelle and vesicle movement. The gamete cytoskeleton has a central role in sperm cell formation and in the reshaping process during gamete movement inside the pollen tube. It consists mostly of microtubules and partially characterized microtubule-associated structures. Actin filaments have recently also been identified. PMID- 1932582 TI - Structural organization and transcription of plant mitochondrial and chloroplast genomes. AB - Experimental evidence is presented showing that the plant mitochondrial and chloroplast genomes are multipartite and, that besides a large circular genomic DNA, they contain subgenomic minicircular and plasmid-like molecules. It is demonstrated that plant mitochondrial and chloroplast DNAs are packaged into deoxynucleoprotein fibrils comprising nucleosome-like and nucleomere-like globules; the fibrils form loops and rosette-like structures with central proteinaceous components. A similar structure is characteristic of the subgenomic DNAs. The basic proteins involved in the formation of nucleosome-like globules are quite different from the nuclear histones, indeed the basic proteins from plant mitochondria and chloroplasts are also distinct. Some of the basic proteins share common antigens with the E. coli HU protein. The genetic code for the mitochondrial and chloroplast genes is universal. The only codon now thought to be different from the universal in the mitochondrial genome is corrected during post-transcriptional mRNA editing. There are two hexanucleotides in the promoters of the chloroplast genes homologous to the sequences in -10 and -35 regions of the prokaryotic genes promoters requisite for transcription. Promoter sequences of the plant mitochondria genes responsible for transcription regulation were not identified. Immunoelectronmicroscopic evidence suggest that mitochondrial and chloroplast RNA polymerases have antigens in common with the beta-subunit of E. coli RNA polymerase. It is shown that the mitochondrial genes are intensely transcribed in the dark and repressed by illumination. Electron microscopy demonstrated that about 70% of plant mitochondria contain numerous RNA polymerase molecules in the dark, but this percentage falls to 10-15% after light exposure. PMID- 1932583 TI - Ultrastructure of cell mediated cytotoxicity. AB - Contact dependent cell mediated cytotoxicity has been found to be executed by lymphocytes, macrophages, and even granulocytes. Cytotoxic effector cells of the lymphatic lineage are divided into cytotoxic T lymphocytes (CTL), mediating MHC related cytotoxicity, and in effectors mediating non-MHC restricted cytotoxicity such as natural killer (NK) cells, T lymphocytes displaying NK-like activity and lymphokine activated killer (LAK) cells. In morphologic studies these cells are hardly to be distinguished: they all show features of large granular lymphocytes (LGLs), which are characterized by a low nuclear to cytoplasmic ratio and azurophilic granules. Ultrastructurally lysosomal granules, showing an electron dense core that is either surrounded by numerous small vesicles or by a small electron translucent halo, have been found. Pore-forming proteins such as perforin, as well as serine esterases and proteoglycans have been pointed out in these granules. Specialties are parallel tubular arrays (PTA) in NK cells and nuclear inclusion bodies in LAK cells. Morphologically two types of killing event may be distinguished. In one way membrane lesions develop at the surface of target cells upon binding of effector cells and in advanced stages of cytolysis the target cells are surrounded by a completely disintegrated membrane. The nuclei, however, show only minor changes. In the other way, called apoptosis, the cell membrane of the targets remains intact, but the nucleus and cell organelles very early disintegrate intracellularly. Whether these morphologically different types of cell killing correspond to the functionally different pathways of cell mediated cytotoxicity remains to be resolved. PMID- 1932584 TI - Soft X-ray contact microscopy of biological materials. AB - Light microscopy (LM) enables biological specimens to be examined without fixation or dehydration but the resolution is insufficient for studies of cell ultrastructure. Electron microscopy (EM) improves the resolution, but requires the specimen to be fixed or frozen, which may cause alterations in cell structure. Using soft X-rays to image specimens improves the resolution, relative to LM, and avoids tissue pretreatment. Staining is not required since within the 'water window' (2.3-4.4 nm), carbon absorbs more strongly than oxygen. The lower attenuation of soft X-rays, relative to electrons, by biological material allows specimens several microns thick to be examined. Several sources for generating water-window X-rays are briefly described and examples of images obtained with each are presented. The specimens imaged include both plant and animal material either in the fixed or natural state. Of the different systems currently used to collect images only contact imaging is considered in detail. By placing the specimen against photosensitive resist, which acts as the image recording medium, an absorption map of the specimen is produced. This latent image is then chemically developed and, after coating, the resist is examined by scanning EM, or, if a replica is produced, by transmission EM. Using laser-produced plasmas such images are produced within a very short exposure time, typically 1-10 nsec, thus avoiding any radiation-induced damage to the specimen which other X-ray imaging techniques may cause. PMID- 1932585 TI - Comparative electron microscopy of basophils and mast cells, in vivo and in vitro. AB - We compared the fine structure and electron microscopic cytochemical findings of basophils and mast cells from humans, guinea pigs, rabbits, mice and rats. The particulate structure was the most frequently observed and most typical structure of human and rabbit basophil granules and of guinea pig mast cell granules. The most prominent feature of guinea pig basophils and murine mast cells was that the fine structure of the granules was homogeneous. The fine structure of the granules in guinea pig basophils resembled that in murine mast cells, while the fine structure of the granules of guinea pig mast cells resembled those in human and rabbit mast cells. In mouse mast cells in culture, the majority of the granules contained small vesicles, which were also observed in human basophils in culture and in mouse basophils in vivo. The degrees of cytochemical reactivity of acid mucopolysaccharides among the species were different. Peroxidase activity was positive in most basophils and in human mast cells. Among mammals, the granules of basophils and mast cells present heterogeneous fine structure. It is of interest that the basophil granules of some species resemble the mast cell granules rather than the basophil granules of other species. PMID- 1932586 TI - Ultrastructure of the apical zone of Euglena gracilis: photoreceptors and motor apparatus. AB - Euglena is an organism that every student of biology has observed; its morphology has been a subject of interest since the early microscopic literature for its enigmatic role of "plant-like" or "animal-like" organism. Therefore, this review has no pretensions to absolute novelty, but, like a journey to the centre of the earth, will attempt to arouse the reader's curiosity by taking him inside the cell Euglena, through the canal opening into the reservoir chamber. In light of the most recent knowledge, though much remains to be clarified, the aim is to provide information from ultramicroscopical studies on the apical zone of Euglena and possible functional meanings of the structures present therein. The survey of these structures is carried on as a study in correlation: TEM of cells after various treatments is correlated with SEM of cells fixed by means of different techniques. Notes on locomotion and other features of cytological and biological interest are added to assist with the comprehension of this microorganism. PMID- 1932587 TI - Techniques for the visualisation of cytoskeletal components in Dictyostelium discoideum. AB - A general description is given of the various techniques that may be used in ultrastructural studies of the cytoskeleton. Electron microscopy of the cytoskeleton of Dictyostelium discoideum serves as a source of examples illustrating the general effects of detergent treatment and fixation techniques. A concise review is given of the structure and function of the actin microfilament system and the cytoplasmic microtubules in Dictyostelium, based on electron microscopical, light microscopical and biochemical studies. Special attention is paid to their involvement in cell movement and chemotaxis. Conventional thin sectioning, fast freezing freeze substitution, whole mounts, freeze fracturing and freeze etching and negative staining techniques are discussed and their respective advantages and limitations are mentioned. A recently developed technique, wet-cleaving, is described which gives promising results in experiments in which the inside of the plasma membrane with the adhering cortical cytoskeleton is studied. This technique may turn out to be useful in high-resolution scanning electron microscopy. A description is given of protocols that proved to be successful in the author's and other laboratories. In a few cases the feasibility of immunogold labelling (illustrated by anti-tubulin labelling of cytoplasmic microtubules) is also dealt with. PMID- 1932588 TI - Ultracytochemistry of the secretory pathway in Saccharomyces cerevisiae defies the established pathway model. AB - The molecular and cell biologic data supporting the established model of the intracellular secretory (transport) pathway for glycoproteins in the yeast Saccharomyces cerevisiae have been reviewed and confronted with our electron cytochemical findings. These in situ findings show a new class of constitutive intracellular conveyors--the coated globules--and also suggest substantial alternatives in the cellular mechanism of the vacuole biogenesis. The controversial question of the Golgi compartment identity in S. cerevisiae is revived. PMID- 1932589 TI - Canadian Cancer Statistics 1991. AB - During 1991, an estimated 109,000 new cases of cancer will be diagnosed in Canada (excluding non-melanoma skin cancer). Estimated cancer deaths in 1991 will total 56,700. Excluding non- melanoma skin cancer, over one in three Canadians will develop some form of cancer during their lifetime, while one in four men and one in five women will die from this disease. These statistics are discussed, as well as cancer risk factors, cancer in children, age and sex distribution of cancer, cancer survival rates, trends in cancer incidence and mortality since 1970, smoking and lung cancer, and cancer among the Inuit and Indians. PMID- 1932590 TI - Measuring the health of Canadians: an agenda for developing health surveys. PMID- 1932591 TI - Patterns and change in Canadian fertility 1971-1988: first births after age 30. AB - An analysis of Canada's changing pattern of births during the period 1971-1988 suggests that the tempo and timing of fertility has changed. Between 1971 and 1988, the number and rates of first births to women in their 30s increased rapidly, and rates for women younger than 25 declined. The rate of first births (first births per 1,000 women) for women 30-34 increased from 11.5 in 1971 to 17.1 in 1981 and to 22.3 in 1988--a 94% increase over the 17 years. The rate for women 35-39 also rose from 3.0 in 1971 to 3.6 in 1981 and 5.9 in 1988--a 97% increase occurring mostly in the 1980s. PMID- 1932592 TI - Cancer incidence and mortality 1985 and 1986. PMID- 1932593 TI - Causes of death 1989. PMID- 1932594 TI - Mortality atlas of Canada: Volume 4--General mortality patterns and recent trends. PMID- 1932596 TI - Therapeutic abortions, Canada and the provinces, 1989. PMID- 1932595 TI - Residential care facilities 1988-89. PMID- 1932597 TI - Trends in hospital inpatient utilization, 1961-1988/89. PMID- 1932598 TI - Physiological occurrence, biosynthesis and metabolism of retinoic acid: evidence for roles of cellular retinol-binding protein (CRBP) and cellular retinoic acid binding protein (CRABP) in the pathway of retinoic acid homeostasis. AB - This article will address recent work on the physiological occurrence, biogenesis and metabolism of retinoic acid and summarize the data that retinoic acid is synthesized in situ in multiple tissues and cell types via enzymes or enzyme complexes that are distinct from the alcohol dehydrogenases. There is now considerable evidence that retinoic acid is an activated metabolite of retinol that supports the systemic functions of vitamin A in vivo. Many studies in vitro, for example, have shown that retinoic acid is the most potent naturally-occurring retinoid with an ED-50 in the range of 1 pM to 10 nM, depending on the assay system. This is below the tissue concentrations of retinoic acid which range from approximately 20-600 nM. Retinoic acid synthesis from retinol in the dog kidney cell line MDCK maintained in serum-free medium is inhibited by the prostanoid, PGE, and the phorbol ester, TPA. In tissues, one pathway of retinoic acid synthesis begins with apo-CRBP stimulating retinyl ester hydrolysis by a microsomal, cholate-independent retinyl ester hydrolase to form holo-CRBP. The holo-CRBP itself is used as substrate by an NADP-dependent, microsomal retinol dehydrogenase to generate retinal, which is converted into retinoic acid by a cytosolic NAD-dependent retinal dehydrogenase. Therefore, cellular retinol binding protein (CRBP) apparently has at least 2 functions in retinoic acid synthesis: the apo form stimulates retinol mobilization from retinyl ester stores; the holo form delivers the retinol via direct transfer to dehydrogenase(s). Retinoic acid is converted into a mixture of at least 4 metabolites by testes microsomes which migrate closely on reverse-phase HPLC with 4-hydroxyretinoic acid, and may be mistaken for either 4-hydroxy or 4-oxo retinoic acid. More rigorous analysis, however, shows that only one of them is 4 hydroxyretinoic acid, and another is 18-hydroxyretinoic acid. Two others remain unidentified. These metabolites are also formed in the presence of excess cellular retinoic acid-binding protein (CRABP), which increases the elimination half-life of retinoic acid, but does not prevent retinoic acid catabolism, suggesting that holo-CRABP may be a substrate for retinoic acid catabolism that modulates the steady-state concentrations of retinoic acid. Thus, both retinoid binding proteins, CRBP and CRABP, may each have direct roles as substrate in the biosynthesis and metabolism of retinoic acid, respectively. PMID- 1932599 TI - Roles for the heliodynamic hormones, all trans retinoic acid and 1 alpha, 25 dihydroxyvitamin D3, in control of the hematopoietic cell cycle. AB - It is now well established that the production of primary hematopoietic cells is controlled at different levels of the biological organization. Bone marrow (BM) stromal cells, the extracellular matrix (ECM), polypeptide hematopoietic growth factors (HGF) as well as endogenous cell-division cycle (CDC) related factors play a dominant role in this control. Recent information suggest that the 2 lipophilic hormones, transRA and 1 alpha,25D3, depending on and/or perhaps mediating solar energy, play a role in the maintenance of BM homeostasis. Here we show that both transRA and 1 alpha,25D3: a) modulate the growth and/or stimulate the adipocytic differentiation of fibroblastic stromal cells (F-CFU); b) inhibit the synthesis and extracellular processing but stimulate the solubilization of matrix collagen; c) modulate the clonal growth of myeloid progenitor cells (GM CFU) in synergy with HGFs; and d) inhibit the production of lactic acid in standard, normal long-term BM cultures (LTBMC). Comparative analysis of normal, preleukemic and leukemic BM cells in LTBMC indicated a positive correlation between the induction of terminal differentiation and reduced lactate production elicited by transRA or 1 alpha,25D3. These results raise a hypothesis according to which the terminal differentiation induced by the helicodynamic hormones is dependent on the mitochondrial aerobic ATP-generating system whose impairment may be a critical step during the process of leukemic transformation. PMID- 1932601 TI - Differential utilization of 2',3'-dideoxyguanosine 5'-triphosphate as a substrate for various DNA polymerases. AB - 2',3'-dideoxyguanosine 5'-triphosphate (ddGTP) was found to be an efficient substrate for DNA polymerase beta when activated DNA was used as the template.primer. Under the optimized reaction conditions with activated DNA, the rate of the incorporation of ddGTP into DNA was almost equal to that of the corresponding normal substrate dGTP. The Km value for ddGTP (1.8 microM) was smaller than that for dGTP (7.8 microM). In contrast, ddGTP was not utilized as a substrate for DNA polymerase gamma with any of the activated DNA and (dC)n.(dG)12 18 as the template primer. Other DNA polymerases such as DNA polymerase alpha, E coli DNA polymerase I and retroviral reverse transcriptase could poorly utilize ddGTP as a substrate. Some of the kinetic properties of DNA polymerase beta revealed toward ddGTP are also described. Since DNA polymerase beta plays a role in DNA repair, the present results predict possible appearance of cytotoxicity or clinical side effect(s) of 2',3'-dideoxyguanosine (ddG), known as a potent inhibitor of human immunodeficiency virus, when ddG is administered to the patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex. PMID- 1932600 TI - Retinoic acid in mono- or combined differentiation therapy of myelodysplasia and acute promyelocytic leukemia. AB - Myelodysplastic preleukemic syndromes (MDPS) and acute promyelocytic leukemia (APL) share a surprising in vivo sensitivity to the hormonally acting 13 cis or all trans retinoic acids (transRA). Here we show that transRA as a monotherapeutic agent induced a stable remission in APL at the third relapse. In MDPS, treatment with prednisone and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25D3) 13 cis RA induced a long-lasting hematological remission. Initially both patients had an impaired BM microenvironment which regenerated on retinoid therapy as judged by reappearance of the Hematon fraction in the BM aspirates. Our preclinical experiments using long-term liquid BM cultures (LTBMC) indicated that several individual patterns of growth and differentiation responses can be induced by combinations of transRA, 1 alpha,25D3 and hemopoietic growth factors (HGFs). The biological responses may vary from complete clonal extinction to a significant growth stimulation of the leukemic blast cell populations. These results further support the importance of preclinical studies in selecting "good" responders for, and excluding "poor" responders from protocols using differentiation therapy. PMID- 1932602 TI - Sarcoidosis: in search of Kveim reactivity in vitro. AB - Granuloma formation in patients with sarcoidosis may be evoked by the intradermal injection of homogenised sarcoid tissue (the Kveim reaction). Attempts to demonstrate an in vitro counterpart of the reaction have been unsuccessful. The cytokine interleukin-2 (IL-2) enhances immune responses in vivo and in vitro. We report here an attempt to amplify the Kveim reaction by the addition of IL-2. We studied the effect of Kveim reagent on the proliferative responses of peripheral blood mononuclear cells (PBMC) in the presence or absence of exogenous IL-2. Twenty-eight patients were studied and 14 healthy subjects served as controls. PBMC were cultured, in vitro, in the presence of Kveim reagent. Recombinant IL-2 or both of these combined. Proliferative responses were measured by [3H] thymidine incorporation. The response of patients' PBMC in the presence of Kveim reagent at a dilution of 1:40 was significantly below the unstimulated response (P less than 0.01). Kveim reagent at a dilution of 1:40 also inhibited the proliferative response of patients PBMC to IL-2 (P less than 0.005); greater dilutions (1:100 and 1:1000) of Kveim reagent were not inhibitory. Responses of PBMC from control subjects (both unstimulated and IL-2 generated) were reduced in the presence of Kveim reagent, however, these reductions were not statistically significant. PMID- 1932603 TI - Malondialdehyde (MDA) level in diabetic subjects. Relationship with blood glucose and glycosylated hemoglobin. AB - The relationships between plasma malondialdehyde (MDA) and metabolic parameters in type I and II diabetic subjects have been studied at different levels of glycemic control. In 67 diabetics (20 type I, 47 type II, aged 53 +/- 1.2) and 40 healthy subjects (aged 47 +/- 1.75), triglycerides (TG), total cholesterol (CT) and C-HDL, fasting blood glucose (FBG), glycosylated hemoglobin (GHb) and MDA were measured. Diabetic population as a whole showed higher MDA plasma levels compared to controls, together with higher FBG, TG, GHb. MDA showed a significant correlation with both FBG and GHb, but was not correlated to plasma lipids. The patients with a poor metabolic control showed the highest plasma MDA concentrations, significantly different from the group with a better control: GHb less than 10% = MDA 2.77 +/- 0.28 nmol/ml - GHb greater than 10% = MDA 4.22 +/- 0.39 nmol/ml (z = 2.10, a less than 0.02); FBG less than 150 mg/dl = MDA 2.74 +/- 0.32 nmol/ml - FBG greater than 150 mg/dl = MDA 4.15 +/- 0.37 nmol/ml (z = 2.22, a less than 0.02). Glycemic equilibrium seemed to influence plasma MDA, increasing free radical production. This phenomenon probably occurred either because of enhanced glycosylation and platelet aggregation, or impairment of cellular antioxidant protective systems. The increased free radical production may play a role in the pathogenesis of metabolic vasculopathy. PMID- 1932604 TI - Correlation of clinical pharmacokinetic parameters of cisplatin with efficacy and toxicity. AB - Twenty-two pharmacokinetic studies were carried out in 11 patients receiving cisplatin (20 mg/m2 per d) associated with etoposide (50 mg/m2 per d), as 5-day continuous infusions, every 4 weeks. Blood was withdrawn at 8:30 am from day 1-5. Within 15 min after taking the blood, an aliquot of plasma was filtered for the ultrafilterable platinum (UP) assay. Total platinum (TP) and UP were assayed by flameless atomic absorption. The plasma concentrations and AUC0-120 h of TP were correlated with those of UP (P less than 0.05 to P less than 0.001). TP concentrations increased significantly during the infusion and with each successive course, whereas the increase of plasma concentration of UP during and between courses was not statistically significant. The responders had significantly higher levels of TP (AUC, concentrations) in the first and second courses than the non-responders. No renal toxicity was observed, nevertheless, the AUC0-120 h of TP and UP were positively correlated with the serum creatinine (P less than 0.05). The digestive intolerance (grade 1-3) was significantly correlated with TP concentrations and AUC0-120 h. There was no statistical difference in UP concentrations either between responders and non-responders in any course, nor between toxic and non-toxic courses. Since etoposide was concomitantly administered, we can formulate the conclusion as follows: no "objective" response was observed in the patients with low TP plasma concentrations and AUC0-120 h. PMID- 1932605 TI - Ocular pharmacokinetics of calcium, chloride and sulphate ions after instillation in the rabbit. AB - The ionic environment of the eye is involved in major biochemical processes which are essential for preserving the integrity of cornea and lens. The purpose of the present study was to determine the intra-ocular penetration and the pharmacokinetic parameters of calcium, chloride and sulphate ions in the cornea, iris-ciliary body (ICB) and lens, after administration by instillation in the rabbit eye. In order to extrapolate our results to the processes occurring in man, we followed a precise instillation protocol using a low volume (5 microliters) of 45Calcium, 36Chloride and 35Sulphate, which is less than the lacrimal volume determined during the palpebral closing and performing manual blinking at a frequency of 2 min-1. The results indicate an immediate trans corneal permeability and a rapid ocular distribution of these ions. We observe that, relative to dose, an important percentage of calcium (67.20 per cent) was entrapped in the cornea; this parameter was less important for chloride (10.19 per cent) and for sulphate ions (3.25 per cent). These values are in agreement with those predicted theoretically for trans-corneal penetration by such compounds. On the other hand, the total degrees of penetration by chloride and sulphate ions in ICB (1.40 per cent and 0.90 per cent, respectively) and lens (0.35 per cent and 0.41 per cent, respectively) are quite similar. Calcium retention is much higher in these tissues (25.39 per cent in ICB and 16.03 per cent in lens).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932606 TI - Pharmacokinetics and oral bioavailability of carbimide in man. AB - A pharmacokinetic study of carbimide, an inhibitor of aldehyde dehydrogenase, used as an adjuvant in the aversive therapy of chronic alcoholism, has been carried out in male human volunteers for intravenous and oral administration. Carbimide plasma concentrations were determined by a sensitive and specific high performance liquid chromatographic method. The intravenous doses administered were 0.1, 0.3, 0.6, and 1 mg kg-1 and linear pharmacokinetics were observed for this dose range. Elimination half-life and total plasma clearance values ranged from 42 to 52 min and from 14.4 to 20.5 ml kg-1 min-1, respectively. After oral administration of 1 and 1.5 mg kg-1 of carbimide, elimination half-life values were 75 and 61 min, respectively, being higher than the corresponding value obtained after 0.3 mg kg-1 doses, i.e. 39 min. In all cases, rapid absorption was indicated by tmax values ranging from 10.5 to 15.5 min. Absorption was not complete, the oral bioavailability being 53 per cent and 70 per cent for the 0.3 and 1 mg kg-1 carbimide dose, respectively. The data indicate that there is a first-pass effect for carbimide. PMID- 1932607 TI - Comparative bioavailability of two flurbiprofen products: stereospecific versus conventional approach. AB - In this randomized, crossover study comparing the bioavailability of a film coated (Ansaid) with a sugar-coated (Froben) 100 mg tablets of racemic flurbiprofen in 23 healthy young men, no significant differences were found for Cmax, tmax or AUC, using a nonstereoisomeric assay for flurbiprofen. Minor differences in the appearance of flurbiprofen in serum during the first 30-min post-dosing period were noted, with Ansaid appearing earlier than Froben. These differences likely reflect dissolution rate dissimilarity between the two products. Stereospecific determinations demonstrate a small (7.8 per cent) but significant difference in AUC of the active S-configuration (Froben greater than Ansaid). No significant differences between Ansaid and Froben were found for tmax or Cmax for the S-flurbiprofen. In bioequivalency studies of chiral drugs, stereospecific approaches provide a more accurate assessment of products. PMID- 1932609 TI - Effect of co-administration of Intralipid on the pharmacokinetics of cyclosporine in the rabbit. AB - The effect of Intralipid co-administration on the pharmacokinetics of cyclosporine (CyA) was studied in NZW rabbits. A single intravenous bolus dose of CyA (10 mg kg-1) mixed with 3 ml of Intralipid was administered to rabbits (n = 4). Control animals (n = 4) received the same dose of CyA without Intralipid. Serial blood samples were collected up to 12 h after the administration of CyA. Concentrations of CyA in plasma were analyzed using a HPLC method. The terminal elimination half-life (t1/2) of CyA was significantly lower with Intralipid administration (191 +/- 25 min) than control (298 +/- 59 min). The total body clearance (ClTOT) and volume of distribution (Vdss) of CyA was reduced by approximately 65-70 per cent with Intralipid administration compared to control. The free fraction of CyA in plasma with and without Intralipid administration was estimated to be 0.05 +/- 0.01 and 0.17 +/- 0.06, respectively. Co-administration of Intralipid with CyA decreased both the ClTOT and Vdss resulting in a rapid elimination, i.e., decrease in a t1/2 of CyA from the body. PMID- 1932608 TI - Pharmacokinetic comparison of a combination tablet of enalapril and hydrochlorothiazide with enalapril and hydrochlorothiazide tablets administered together and separately. AB - Enalapril and hydrochlorothiazide (HCT) are established single agent treatments for mild hypertension and cardiac failure and are a potent combination in more severe or resistant cases. We have compared the pharmacokinetics of enalaprilat (the active metabolite of enalapril) and HCT in a four-way comparison of a combination tablet of enalapril (10 mg)/HCT (25 mg) with a single dose of an enalapril tablet (10 mg), a single dose of a HCT tablet (25 mg) and simultaneous administration of separate tablets of enalapril (10 mg) and HCT (25 mg) in normotensive volunteers (n = 12, 21-26 years). Each subject received all four treatments and the study was conducted as a randomized, latin square, open design with at least 1 week washout between studies. Overall, HCT was bioequivalent under all conditions and enalaprilat was bioequivalent when given in combination with HCT either as one tablet or as two separate tablets. However, when given with HCT, the mean AUC and Cmax of enalaprilat were reduced up to 20 per cent compared with enalapril administered alone. This is unlikely to be of clinical significance as the differences did not reach statistical significance and the total enalaprilat excreted in the urine over 96 h was similar after all treatments. PMID- 1932610 TI - Prednisone and prednisolone interconversion in the rabbit utilizing unbound concentrations. AB - Prednisolone (POH) and prednisone (PO) were both administered via seven different intravenous infusions (three POH and four PO) in each of six rabbits to obtain steady state. Bolus doses of POH and PO were also administered to four of the rabbits. Plasma samples of POH and PO were analyzed by normal phase HPLC. Unbound concentrations of both compounds were estimated in each rabbit using equilibrium dialysis and computer fit of the nonlinear or linear binding. The unbound fraction of POH ranged between 3 and 15 per cent from tracer to total concentrations of 2000 micrograms-1. The unbound fraction of PO ranged between 23 and 34 per cent and appeared nonlinear for four of the rabbits. The mean apparent unbound clearances of POH ranged from 4.4 to 6.1 lh-1kg-1 and from 4.1 to 5.9 lh 1kg-1 for PO, and were dose-independent for both compounds. The available fraction of POH from PO was 50 to 70 per cent and independent of dose. The available fraction of PO from POH averaged 44 per cent at the low infusion rate decreasing to 16 and 20 per cent at the medium and high infusion rates. Although saturability in the formation of PO from POH was noted, this nonlinear step is apparently not large enough to induce observable changes from linearity in the overall disposition of unbound POH. PMID- 1932611 TI - Pharmacokinetics of benzydamine after intravenous, oral, and topical doses to human subjects. AB - The pharmacokinetics of the anti-inflammatory drug benzydamine were determined after intravenous infusion of 5 mg to six healthy male subjects. Benzydamine was characterized as a drug of relatively low systemic clearance (ca. 160 ml min-1) but high volume of distribution (ca. 1101); the apparent terminal half-life in plasma was ca. 8 h. Benzydamine was well absorbed after oral administration, as indicated by a mean systemic availability of 87 per cent. However, absorption of the drug was low (less than 10 per cent of the dose) after its use by male subjects as a mouthwash, or after its application to female subjects as dermal cream and vaginal douche preparations. The data suggest that benzydamine is generally not well absorbed through the skin and non-specialized mucosae, thereby limiting unrequired systemic exposure to this drug when it is used by these routes. PMID- 1932612 TI - Relative bioavailability of oral sustained-release and regular-release oxprenolol tablets at steady-state. AB - The relative bioavailability of a test sustained-release (SR) oxprenolol tablet against an approved regular-release (RR) tablet has been investigated at steady state. In a randomized two-way crossover study, one tablet of 160 mg SR oxprenolol once every 24 h and one tablet of 80 mg RR oxprenolol once every 12 h were given to 12 healthy volunteers for 5 days. Blood samples were collected from each subject just prior to each dose-administration on days 1 through 4, and at scheduled time points on day 5 and analysed for oxprenolol concentration using HPLC. The SR tablet resulted in 42 per cent reduction in mean peak drug levels (p = 0.0341) and a statistically non-significant 14 per cent increase in mean trough levels (p = 0.8357) than the RR tablet. However it required 160 per cent longer time to reach average steady-state concentrations (Css) on day 5 (1.38 h for SR versus 0.53 h for RR; p = 0.0205). The mean area under the plasma drug concentration-time curve at steady state (AUC96-120) with the SR tablet was approximately 18 per cent lower than that observed with the RR tablet, and the degree of fluctuation (DF) was reduced by 30 per cent (2.81 for SR versus 4.11 for RR; p = 0.0069). On average, a single dose of SR tablet and two doses of RR tablets maintained the drug levels above a constant Css of 204.6 ng ml-1 for 7.88 and 7.65 h, respectively (p = 0.3513). PMID- 1932613 TI - Pharmacokinetics of diltiazem and propranolol when administered alone and in combination. AB - Multiple oral doses of diltiazem (DTZ) and propranolol (PPL, 60 mg every 8 h daily for 13 doses) were administered to 14 healthy volunteers alone and in combination on three separate occasions. Serial blood samples were collected up to 24 h after dose 13 on day 5 to determine possible pharmacokinetic interactions between the two drugs. When administered alone, DTZ concentration peaked at 161.4 ng ml-1 3 h following the final dose with an elimination half-life of 6.1 h. DTZ oral clearance was 65.1 l h-1. PPL did not affect DTZ oral clearance and half life during the combination treatment. However, DTZ tmax was extended from 2.9 h to 3.5 h (p less than 0.05) and Cmax was 144.7 ng ml-1. Unlike the parent drug DTZ, desacetyldiltiazem (DAD) plasma profile was elevated during the combination treatment. DAD Cmax and AUC both increased approximately 20 per cent (p less than 0.05). PPL pharmacokinetics were altered as well. Oral clearance of PPL decreased from 80.4 l h-1 to 61.0 l h-1 while the half-life increased from 5.9 h to 8.0 h (p less than 0.05). PPL Cmax increased from 155.1 ng ml-1 to 167.5 ng ml-1. PMID- 1932614 TI - The pharmacokinetics of atropine and diazepam in sheep: intramuscular co administration. AB - The purpose of this study was to determine whether the co-administration of atropine and diazepam affect the rate and extent of absorption of either drug. A triple crossover pharmacokinetic study using adult sheep was conducted. Each of nine animals received single injections of atropine (2 mg), diazepam (10 mg), and a combination of the two compounds weekly over a 3-week period. The combination of the drugs was injected into a single intramuscular site through a specially designed tandem syringe. Blood samples were obtained from time 0 to 300 min post injection. Serum samples were analyzed for atropine by radioimmunoassay and for diazepam by gas chromatography/mass spectrometry. Pharmacokinetic parameters were evaluated by non-compartmental analysis. The co-administration of atropine and diazepam intramuscularly in sheep caused a delay in the time to reach maximal concentration of atropine. However, at the time when a single injection of atropine reached its maximum serum concentration, 92 per cent of that concentration was reached by atropine in the presence of diazepam. Additionally, no difference was detected in the rate or extent of diazepam absorption when administered intramuscularly in combination with atropine at the same site. PMID- 1932615 TI - Pharmacokinetics and bioavailability of papaverine HCl following intravenous, peroral, rectal, vaginal, topical and buccal administration in beagle dogs. AB - This in vivo study was designed to obtain bioavailability data and a definite pharmacokinetic profile of papaverine HCl in Beagle dogs following intravenous (IV), peroral (PO), rectal, vaginal, topical, and buccal administration of different papaverine HCl formulations. Blood samples were analyzed by high performance liquid chromatography. The pharmacokinetic parameters were determined using either a curve fitting program (RESID) or a compartment model independent program (AUC-RPP). The plasma concentration-time profiles show that papaverine HCl pharmacokinetics is best described by an open two-compartment model. The absolute bioavailability of papaverine HCl was determined to be 57.2 per cent, 25.2 per cent, 53.2 per cent, 3.2 per cent and 7.5 per cent, respectively, following P.O., rectal, vaginal, topical and buccal administration. PMID- 1932616 TI - Dermal absorption of niclosamide in rats and minipigs. AB - The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine. PMID- 1932617 TI - Immunological effects of tumor vaccines: III. Influenza virus oncolysates inhibit the TPA induced activation of peripheral blood mononuclear cells. AB - This paper investigates the effects of tumor vaccines on T cell proliferation induced by 12-0 tetradecanoylphorbol-13-acetate (TPA). Viral oncolysate (VO) tumor vaccines containing inactivated influenza virus A significantly inhibited TPA-induced T cell proliferation. In contrast, a control tumor vaccine (CO) that contained the same cellular components as VO but lacked influenza virus did not affect the TPA-induced proliferation. These effects were also observed with peripheral blood mononuclear cells (PBMC) from ovarian cancer patients, although VO and CO each induced significant and similar levels of proliferation in these cells in the absence of TPA. Protein kinase C (PKC) is a pivotal enzyme in signal transduction pathways that control cell proliferation, and TPA is a specific activator of PKC. VO and CO showed differential effects on the inhibition of purified protein kinase C (PKC). These studies demonstrate the antagonistic effects of different tumor vaccines on T lymphocyte proliferation and suggest that influenza virus A or virus-modified cellular components may interfere with signal transduction in the immune cells of the recipient of the tumor vaccine. PMID- 1932618 TI - An in vivo animal model to study chronic adriamycin cardiotoxicity: a P-31 nuclear magnetic resonance spectroscopy investigation. AB - The mechanism responsible for adriamycin induced cardiotoxicity is unknown. We have developed an in vivo rabbit model for use with P-31 nuclear magnetic resonance spectroscopy which allows serial investigations of the drug's effects on myocardial metabolism. Eleven animals were studied over a 10 week period and changes in intracellular pH and phosphate metabolites were observed. The magnitude of changes in pH and inorganic phosphate were the best indicators of the severity of the cardiomyopathy. The results are consistent with an adriamycin induced degeneration of myofibrils rather than a severe metabolic impairment. PMID- 1932619 TI - Cytogenetic characterization of eight human lymphoblastoid cell lines. AB - Cytogenetic analyses of eight human lymphoblastoid cell lines that were established by a new procedure using B-cell growth factor (BCGF) and interleukin 4 (IL-4) revealed that three cell lines (37.5%) showed structural anomalies in more than 97% of their metaphases, whereas others were predominantly normal diploid. Our results indicate that a) the structural anomalies seen in three cell lines were not induced by culture technique but were constitutional defects present in donors' peripheral blood samples; b) one donor, whose blood gave rise to cell line BCDI, is a constitutional mosaic because both normal diploid and altered metaphases were present; and c) genetic instability should be monitored in regular blood donors because some of them may harbor blood-mediated clastogen or chromosome breakage factor(s) that could induce higher rates of recombinations in somatic cells of some recipients and thus may potentiate such individuals to develop certain types of malignancies. PMID- 1932620 TI - Increased response to cisplatin after long-term serial passage of a squamous cell carcinoma xenograft. AB - We have retrospectively investigated the response to cisplatin of a squamous cell carcinoma of the head and neck xenografted to nude mice during nine years of serial transplantation. Tumour growth rate decreased gradually. After nine years and over 100 passages, there was a sudden increase in cisplatin sensitivity. Histopathological examination showed that, of two histopathologically different subpopulations present in earlier passages, the predominant one was no longer detectable. The DNA-index did not change. PMID- 1932621 TI - Influence of treatment with the immunomodulatory effective dose of the beta galactoside-specific lectin from mistletoe on tumor colonization in BALB/c-mice for two experimental model systems. AB - Mistletoe extracts have approval for clinical application. This warrants the quest for the definition of the active substances to optimize their application. Thus, the extent of immunomodulating and antimetastatic activity of the beta galactoside-specific lectin from mistletoe extract (ML I) was investigated. In BALB/c-mice regular subcutaneous (s.c.) injections of small nontoxic doses of ML I yielded significant enhancement of peritoneal macrophage activity, as measured in chemiluminescence assays, as well as significant weight gain of thymus. Spleen weight, however, increased without statistical significance. To evaluate the anti metastatic activity of ML I we intravenously (i.v.) inoculated sarcoma L-1 and fibrosarcoma RAW 117-H 10 cells which cause tumor colonization of lungs and livers in BALB/c-mice, respectively. After regular s.c. administration of ML I, the number of lung and liver tumor colonies significantly decreased in both experimental tumor models as compared to control mice which received injections of saline solution. Accordingly, ML I can be regarded as a potent immunomodulating and antimetastatic substance, which seems to be promising for clinical trials in human oncology. PMID- 1932622 TI - A comparison of the effects of repeated administration of cyclophosphamide, cytosine arabinoside or their combination on smooth and skeletal muscle. AB - The pharmacological effects of repeated administration of 2 mg Kg-1 cytosine arabinoside, 40 mg Kg-1 cyclophosphamide or their combination, all given once weekly for 5 weeks, have been investigated in chicks. Cyclophosphamide did not affect responses to noradrenergic nerve stimulation or phenylephrine, depressed responses of the expansor secundariorum muscle to acetylcholine but sensitised the muscle to direct stimulation. Cytosine arabinoside depressed noradrenergic transmission and enhanced responses of the expansor muscle to phenylephrine and acetylcholine. The combination of both drugs enhanced responses to noradrenergic nerve stimulation due to increased alpha-adrenergic receptor mediated contraction and direct muscle sensitisation. Cyclophosphamide, cytosine arabinoside or their combination produced a non-specific depression of the upper oesophagus and ileum. The exception was the marked increase in response of the ileum from the combination group to agonist drugs, indicating synergism. The non-specific skeletal muscle depressant actions of cyclophosphamide and the combination groups were more pronounced than that of the cytosine arabinoside group. PMID- 1932623 TI - Effect of a 9 mT pulsed magnetic field on C3H/Bi female mice with mammary carcinoma. A comparison between the 12 Hz and the 460 Hz frequencies. AB - In a previous experiment, the exposure of tumoral C3H/Bi female mice to a 9 mT, 460 Hz pulsed magnetic field led to an increase in the length of survival in the late period of the disease; this might be due to a hampered metastatic process. In the present study 27 controls and 52 exposed mice were treated with the same protocol (a 10-minute exposure, 3 non-consecutive days a week, from 2-3 weeks after the tumors appeared until death) but with a 12 Hz PMF. In this experiment the 12 Hz PMF appeared to increase length of survival times in the early period of the disease. PMID- 1932624 TI - The use of the Nb rat in combination chemotherapeutic experiments for prostate cancer. AB - The Nb rat adenocarcinoma model has been used to evaluate combination chemotherapy. The Nb rat is a model system in which one can measure tumor regression, tumor metastasis and response to treatment. Combination treatment decreased metastasis and increased the incidence of regression in this triple chemo treatment program of 5-FU, Adriamycin and Cisplatinum. PMID- 1932625 TI - Effect of intravenous feeding on wound healing in starvation: an experimental study on the rabbit. AB - The effects of modified protein sparing therapy (PSP) and total parenteral nutrition (TPN) on total and wound metabolism were studied for 96 hours after laparotomy and a small gastric excision in 40 rabbits starved for seven days. A further eight starved and eight non-starved animals served as controls for the blood variables. Normal healing up to day 14 was studied in 20 non-starved animals. The difference in deaths and animals in poor condition, 42.1 per cent in PSP and 18.6 per cent in TPN, respectively, was clear but statistically non significant. PSP led to a lower mean serum albumin concentration than TPN, 25.7 +/- 3.7 (SD) and 28.7 +/- 3.0 (p = 0.02), respectively. The animals receiving PSP excreted significantly more 3-methylhistidine. TPN maintained a positive nitrogen balance, but PSP produced a negative one. The collagen content of the skin scar was lower after PSP (3.1 +/- 0.7 mg) than after TPN (4.5 +/- 1.3 mg) (p less than 0.05), the latter coming close to the level for normal 4-day healing, 4.5 +/- 1.2 mg. Prolyl 4-hydroxylase (PPH) activity showed no difference. No inter-group differences in collagen were found in the stomach. Both regimens totally reversed the starvation-induced decrease in PPH activity in the stomach, but only partially in skin. Thus TPN produced better total and skin wound metabolism after laparotomy and starvation than did PSP. No differences in visceral wound healing were observed. PMID- 1932626 TI - Mechanism of the cytostasis mediated by blood unstimulated neutrophils on syngeneic rat colon cancer cells. AB - Non-activated polymorphonuclear neutrophils (PMNs) isolated from the blood of non stimulated rats were spontaneously and selectively cytostatic in vitro against a syngeneic colon cancer cell line. In this experimental model, the mechanism of PMN-mediated cytostasis did not depend on oxidative metabolites, but involved soluble factor(s), possibly granule proteases. PMID- 1932627 TI - Cardiotoxicity of anthracyclines. AB - This study describes the effects of some anthracyclines (adriamycin, 4 epiadriamycin and esorubicin) on isolated, electrically driven left guinea pig atrium in normodynamic or hypodynamic (Tyrode solution with 0.1 g/1 CaCl2) conditions. Exposure for 60' to the anthracyclines caused a depression of contractile force and of maximal rate of tension development (df/dt). The statistical analysis of data showed an equivalent inhibitory effect between adriamycin and esorubicin, whereas 4-epiadriamycin has in normodynamic conditions greater negative inotropic effects significantly different from that of the two other drugs. Thus the lower toxicity of 4-epiadriamycin observed in vivo by other authors may probably be imputed to a lower concentration of the drug in the heart. The cardiac depressant effects induced by anthracyclines in vitro, as previously reported, are antagonized by new cardiotonic agents whose mechanism of action can be related to an increase in calcium activity in myocardial tissue. PMID- 1932628 TI - Zinc, carotene, and retinol in melanoma and non-melanoma skin cancer. AB - Serum zinc, beta-carotene, retinol, retinol binding protein and prealbumin were measured in 22 cutaneous melanoma patients at diagnosis and in 17 patients with 1 or more basal cell carcinomas of the skin recently removed. The indices measured were found to distinguish melanoma patients from non-melanoma patients with a high level of accuracy. Moreover, the predictability of zinc depends on the level of beta-carotene, and this dependence differs between melanoma and non-melanoma patients. PMID- 1932629 TI - Evaluation of genotoxicity of clofazimine, an antileprosy drug, in mice in vivo. III. Sister chromatid exchange analysis in bone marrow cells. AB - The potential genotoxicity of an antileprosy drug, clofazimine, was evaluated in mice in an in vivo model by sister chromatid exchange (SCE) analysis. Three different dose levels (4, 20 and 40 mg/kg) were tested, and the animals were treated once daily for 15 days. Sister chromatid differential staining was done by BrdU-tablet implantation and FPG technique. All the doses tested here elevated the SCE frequencies significantly and the increases showed a significant positive correlation with the doses. The results confirm our earlier findings based on metaphase analysis and micronucleus test in the same species. PMID- 1932630 TI - Dihydrofolate reductase gene expression characterized by the PCR assay in human leukemia cells. AB - A modified enzymatic amplification (PCR) method has been used to detect overexpression of the dihydrofolate reductase gene in human leukemic cells resistant to methotrexate (MTX) from both patient samples and cell lines in culture. Quantitation of DHFR mRNA by the PCR assay has been demonstrated to be more accurate and more sensitive than Northern blotting. This assay be useful in screening patients relapsing with drug resistance. PMID- 1932631 TI - Immunosuppression by an immunogenic immunomodulating mycobacterial fraction is correlated to changes in phenotype distribution of murine lymphoid cells. AB - Previously reported studies revealed that extensive immunization with the Methanol Extraction Residue (MER) of BCG tubercle bacillus in Incomplete Freund's Adjuvant (IFA) induced marked suppression of T and B cell functions in vivo and in vitro. The purpose of the present work was to determine whether immunosuppression induced by hyperimmunization with MER is correlated with changes in morphological characteristics and in phenotype pattern of spleen and peritoneal lymphoid cells. Hyperimmunization with MER resulted in a marked increase in the number of spleen cells and in enlargement and granulation of spleen and peritoneal cells. Similar changes in size and granulation were also observed in isolated fractions of splenic T and B cells. Extensive immunization with MER also induced marked decrease in the total number of T cells (Thy 1,2 positive). The decrease in T cells was observed in all three T-cell subsets investigated: Lyt-1, Lyt-2 and L3T4 positive. Although the number of splenic B cells was decreased in samples (10,000 cells), taken from MER hyperimmunized mice, this decrease was compensated by overall increase in the number of spleen cells. The marked decrease in the percentage of splenic T cells was counterbalanced by marked increase in the splenic macrophage population: increase in MAC-1, MAC-2 and MAC-3 positive cells. It is concluded that extensive immunization with MER induces morphological changes in spleen and peritoneal cells, marked decrease in the number of splenic T cells and marked increase of the splenic macrophagic population. It is postulated that these changes are correlated with induction of immunosuppression by a similar procedure of extensive immunization with the agent. PMID- 1932632 TI - Ammonium transport in the kidney: new physiological concepts and their clinical implications. AB - This article is based on a Basic Science Symposium presented at the 23rd Annual Meeting of the American Society of Nephrology. New information on the segmental transport of ammonium by the proximal tubule, the thick ascending limb of Henle's loop, and the collecting duct is integrated into a thesis that NH4+ excretion is controlled by the rate of production, by diffusion of NH3 along gradients established by proton secretion, and by active transport of NH4+. These new concepts are applied to a novel explanation of the pathogenesis of distal renal tubular acidosis. PMID- 1932633 TI - Cyclosporine-induced renal dysfunction: correlations between cellular events and whole kidney function. AB - The main adverse reaction to the immunosuppressive drug cyclosporine is dose dependent renal dysfunction. Although renal vasoconstriction without major tubular dysfunction is usually noted, recent studies have demonstrated an inhibition of renal cortical microsomal protein synthesis. Sprague-Dawley rats and appropriate pair-fed controls were given cyclosporine orally in doses of 5, 10, 25, and 50 mg/kg/day for periods up to 10 days. A dose-dependent decline in glomerular filtration rate and effective renal plasma flow was maximal by day 3 and did not worsen despite continued dosing. Microsomal protein synthesis as measured by [3H]leucine incorporation was also depressed in a dose-dependent fashion; however, inhibition did not reach the nadir until day 4, 1 day after renal dysfunction was established. When cyclosporine was discontinued, microsomal protein synthesis was normalized by 4 days after drug withdrawal; in contrast, the return of glomerular filtration rate and effective renal plasma flow to normal required 8 days after drug discontinuation. Tubular function as measured by fractional excretion of lithium, enzymuria, and urinary osmolality was well maintained despite the depression of renal hemodynamics. There was no evidence of tubular necrosis by light or electron microscopy. Although cyclosporine produces reductions in renal microsomal protein synthesis, measured by "run-off" translation assays, these effects appear unlikely to be the direct cause of acute renal dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932634 TI - Effect of myo-inositol on cell proliferation and collagen transcription and secretion in proximal tubule cells cultured in elevated glucose. AB - Tubulointerstitial lesions often develop in the kidneys of patients and experimental animals with diabetes mellitus. In an in vitro model of diabetic renal disease, it has been previously demonstrated in this laboratory that elevated glucose levels stimulate procollagen transcription and secretion in proximal tubule cells in culture while inducing cellular hypertrophy and reducing cellular proliferation. Previous experiments in other tissues have suggested that myo-inositol supplementation, probably by reversing a disturbance in cell myo inositol metabolism related to increased activity of the polyol pathway, reverses the effects of glucose on cell function. We tested the effect of myo-inositol supplementation on proximal tubule cells in culture in the presence of elevated medium glucose level. Incubation in 450 mg/dL of glucose media reduced cell proliferation; 450 mg/dL of glucose plus myo-inositol (800 microM) increased proliferation, returning the value to that seen in cells incubated in 100 mg/dL of glucose. Incubation in 450 mg/dL of glucose media increased type IV and type I procollagen mRNA levels and peptide secretion rates compared with those seen in cells incubated in medium containing 100 mg/dL of glucose. This glucose-induced stimulation of procollagen mRNA levels and procollagen secretion was not observed when the elevated glucose medium was supplemented with 800 microM myo-inositol. On the other hand, myo-inositol supplementation did not prevent the glucose induced cellular hypertrophy: there was no reduction in the increased leucine incorporation and cellular protein content. Cell incubation in 450 mg/dL of glucose media did not lead to a measurable decrease in total cellular myo inositol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932635 TI - Effects of dietary protein intake on muscle protein synthesis and degradation in rats with gentamicin-induced acute renal failure. AB - In the study presented here, the muscle protein synthesis and degradation in gentamicin-induced acute renal failure were examined in rats fed a low (7%)-, normal (22%)-, and high (35%)-isocaloric protein diet. Male Sprague-Dawley rats were fed equivalent amounts of these diets for 10 days and then received daily subcutaneous injections of either 1 mL of sterile isotonic saline or 100 mg/kg of gentamicin for 7 consecutive days. The rats were sacrificed the following day, and epitrochlearis muscles were obtained for measurement of protein turnover. The serum creatinine in each of the gentamicin-treated groups were significantly higher than that in the saline-treated controls but were no different from each other. Muscle protein synthesis (calculated from the incorporation of radiolabeled (U-14C) phenylalanine) was slightly but not significantly decreased in gentamicin-treated rats as compared with that of the corresponding saline controls in each of the dietary groups. Net protein degradation (the rate of tyrosine release into media) in the 7 and 22% gentamicin-treated groups was similar to that in the corresponding saline controls. In contrast, net protein degradation was significantly greater in the 35% gentamicin group of rats when compared with that in the 7 and 22% gentamicin groups and its own control. In the 7 and 22% saline- and gentamicin-treated protein groups, there was a reduction in net protein degradation in response to insulin. In contrast, the net protein degradation continued to remain significantly elevated in the 35% gentamicin treated group, despite addition of insulin, when compared with that in the 7 and 22% gentamicin groups and its own control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932636 TI - The beneficial effects of thyroxine on nephrotoxic acute renal failure in the rat. AB - We were able to confirm previous studies demonstrating that administration of thyroxine is capable of ameliorating the severity of acute nephrotoxic renal failure in the rat. Nephrotoxic acute renal failure was induced by the subcutaneous injection of potassium dichromate (6.25 mg/kg) into Sprague-Dawley rats. Twenty-four hours after this injection, rats received an intraperitoneal injection of either thyroxine (80 micrograms/kg body wt) or normal saline. Forty eight hours after the potassium dichromate injection, renal clearance studies were performed. Inulin clearance was significantly higher in the thyroxine treated than in the saline-treated acute renal failure rats: 1.12 +/- 0.13 (SEM) mL/g versus 0.75 +/- 0.07 mL/min/g kidney wt (P = 0.025). Thyroxine treatment also effected an increase of p-aminohippuric acid extraction from 0.23 +/- 0.03 to 0.33 +/- 0.02 (P = 0.011) and a decrease in the fractional excretion of sodium from 0.38 +/- 0.21 to 0.11 +/- 0.03% (P = 0.037 by Mann-Whitney U test). In order to investigate one potential mechanism of the beneficial effect of thyroxine we studied renal tubular regeneration in this model of acute renal failure. Renal cortical uptake of labeled thymidine into DNA was significantly increased 48 h after the injection of potassium dichromate, and thyroxine administration further enhanced this repair process: 53.9 +/- 3.6 versus 81.4 +/- 5.3 dpm/200 pg of DNA (P = 0.0033). PMID- 1932637 TI - The glomerulopathy of homozygous sickle hemoglobin (SS) disease: morphology and pathogenesis. AB - This morphologic and morphometric study of native-kidney biopsies of six homozygous sickle hemoglobin (SS) nephrotics defines a distinctive glomerulopathy of focal sclerosis developing in maximally hypertrophied glomeruli. In each biopsy, two patterns of segmental glomerulosclerosis were observed: a "collapsing" pattern and an "expansive" pattern. Morphologic analysis comparing group mean glomerular (Bowman's capsular) diameters indicates that glomeruli in SS are routinely markedly enlarged whether nephrotic (group SSN, 233.6 mu +/- SE of 25.3 [N = 6]) or not (control group SSC, 243.5 mu +/- SE of 12.5 [N = 5]). These values are significantly larger when compared with those of matched normal controls (group NC, 158.0 mu +/- SE of 12.7 [N = 6]) or to matched patients with idiopathic focal glomerulosclerosis (group IFS, 188.2 mu +/- SE of 17.9 [N = 6]). Furthermore, based on a previous study, it is most likely that glomerular enlargement in SS represents the maximal hypertrophy attainable in humans. Correlating observations of renal homografts in two sickle hemoglobin patients that developed segmental sclerosis of only the collapsing pattern soon after transplantation, it is proposed that in homozygous sickle hemoglobin nephrotics the collapsing pattern of segmental glomerulosclerosis represents an initial but progressive obliteration of the glomerular capillary bed by red blood cell sickling which cannot be compensated by further glomerular hypertrophy. Hemodynamic glomerular injury then supervenes from the sustained or increasing hyperfiltration in a diminishing capillary bed, manifesting morphologically as the expansive pattern of sclerosis. PMID- 1932638 TI - Effect of dietary chloride intake and the ability of the kidney to excrete a base load. PMID- 1932639 TI - Mechanisms of vascular injury: the emerging role of the endothelium. AB - Evidence is increasing that vascular tone is highly dependent on the health of the endothelium and on the delicate balancing act between endothelium-derived relaxing and endothelium-derived contracting factors. Moreover, there is also evidence supporting the notion that the same factors which affect vascular tone also regulate, either in an autocrine or paracrine fashion, changes in vascular architecture. Synthesis and release of both endothelium-derived relaxing and contracting factors are affected by a number of physiologic and therapeutic agents as well as by other factors, among them vascular injury in disease states such as atherosclerosis, hypertension, diabetes, and acute renal failure. A number of trials indicate that therapeutic intervention may be capable of modulating the synthesis and release of these substances and the balance between the two as well as influencing the processes which control vascular remodeling. PMID- 1932640 TI - The effects of calcium antagonists on renal hemodynamics, urinary protein excretion, and glomerular morphology in diabetic states. AB - Numerous animal studies have been performed in the early stages of diabetic renal disease documenting beneficial effects of angiotensin converting enzyme inhibitors. Over the past 5 yr, a number of animal and human studies show similar results with certain calcium antagonists. However, the data with calcium antagonists are not as consistent as that with angiotensin converting enzyme inhibitors. This article will review all of the pertinent clinical and laboratory studies involving these classes of agents in the course of diabetic nephropathy. Emphasis is placed on explaining divergent results between animal and human studies with regard to renal hemodynamic, histologic, and antiproteinic effects. PMID- 1932641 TI - Calcium antagonists and renal hemodynamics: implications for renal protection. AB - During the past decade, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of this preparation to vasoconstrictor agents. Our recent studies with the isolated perfused hydronephrotic rat kidney model, which permits visualization of afferent and efferent arterioles, have demonstrated that the augmentation of glomerular filtration rate observed in the isolated perfused kidney is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in patients with impaired renal hemodynamics. Such disorders include radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the effects of calcium antagonists on renal blood flow commend their use in the management of essential hypertension. PMID- 1932642 TI - Pathophysiology and treatment of posttransplant hypertension. AB - Post-renal transplant hypertension remains a common problem. The most frequent causes now are chronic rejection and cyclosporine-induced hypertension. Before the development of cyclosporine, renin-dependent hypertension was the dominant pathophysiological mechanism but now, with the widespread use of cyclosporine, a salt-dependent mechanism is the major one. In severe "inappropriate" hypertension, potentially surgically remediable causes such as renal artery stenosis of the allograft artery or renin release from the native kidneys should be considered. Cyclosporine causes hypertension in normal subjects and in all solid organ transplants. The most likely mechanism is renal vasoconstriction with subtle retention of sodium chloride together with systemic vasoconstriction. The vasoconstriction, as yet, is not associated with any specific vasoconstricting agent nor does there appear to be a specific antagonist. Indeed, increased sensitivity to many different vasoconstrictors has been demonstrated. The major site of vasoconstriction appears to be in the afferent arteriole, and optimum antihypertensive therapy is probably provided by calcium channel blockers if the hypertension is due to cyclosporine. Because post-renal transplant hypertension is often multifactorial in origin, however, it is not surprising that the use of combined antihypertensives is often necessary. PMID- 1932643 TI - Cyclosporine-induced chronic nephropathy: an obliterative microvascular renal injury. AB - Physiologic and morphologic techniques have been used to study kidneys of 200 cardiac transplant recipients treated with either low- or high-dose cyclosporine. After 12 months, both low- (4.6 +/- 0.4) and high-dose cyclosporine (6.3 +/- 0.3 mg/kg/24 h; P less than 0.01) were associated with depression of glomerular filtration rate below values in a third group of 100 recipients never exposed to cyclosporine by 40 to 47%. Determination of renovascular pressures and flows as well as analysis of transglomerular sieving of dextrans revealed renal vascular resistance in cyclosporine-treated recipients to be elevated greater than twofold, due largely to an increase in preglomerular resistance. Morphologic changes in renal tissue of both cyclosporine groups included an occlusive afferent arteriolopathy with downstream collapse or sclerosis of glomeruli. Ischemic nephrons were associated with patchy fibrosis of the surrounding interstitium. Follow-up for up to 9 yr reveals persistent but stable azotemia, on average. Longitudinal physiologic studies over a 48-month period (N = 15) during which cyclosporine was reduced in dosage (to 3.1 +/- 0.3 mg/kg) or withdrawn revealed a persistently reduced but constant level of glomerular filtration rate. Increasing ischemic glomerular collapse and sclerosis were observed at repeat renal biopsy. Remnant (spared) glomeruli exhibited hypertrophy; presumably elevated single nephron glomerular filtration rate maintained two-kidney glomerular filtration rate constant despite the declining fraction of functional glomeruli. By actuarial analysis, the cumulative incidence of end-stage renal failure in cardiac transplant recipients treated at this institution from 1980 onwards with continuous cyclosporine therapy has reached 10%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932644 TI - Salt sensitivity in hypertension: implications for the kidney. AB - The role of dietary sodium in the pathogenesis of essential hypertension has stimulated a great deal of interest and investigation in recent years. There are epidemiologic studies in the literature that suggest a link between dietary sodium intake and the prevalence of hypertension. However, not all patients are prone to the development of hypertension in response to dietary sodium. Therefore, a distinction between salt sensitivity and salt-resistant essential hypertension has evolved from this observation. The mechanisms which related dietary sodium to the pathogenesis of essential hypertension are not clearly defined, although it appears that inborn errors of renal sodium handling, along with certain components of the sympathetic nervous system, may be involved. Furthermore, intracellular sodium and its transport mechanisms have been implicated in the pathogenesis of hypertension associated with dietary sodium. Finally, there appears to be a correlation between dietary sodium, salt sensitivity, and the progression of renal disease. That is to say, patients with salt-sensitive essential hypertension appear to demonstrate a more relentless course to end-stage renal disease. This tendency may be related to deranged hemodynamic adaptation of the renal circulation in response to dietary sodium intake and the resulting rise in systemic blood pressure. The mechanism for this derangement of renal hemodynamic adaptation in salt-sensitive hypertensives remains to be determined. PMID- 1932645 TI - Can the anesthesiologist reduce myocardial morbidity after vascular surgery? PMID- 1932646 TI - Significance of mildly elevated creatine kinase (myocardial band) activity after elective abdominal aortic aneurysmectomy. AB - The clinical significance of mildly elevated creatine kinase (CK) myocardial band (MB) enzyme levels in patients undergoing elective repair of an abdominal aortic aneurysm was evaluated retrospectively in 348 patients. For each patient, preoperative and postoperative electrocardiograms (ECGs) were interpreted blindly for left ventricular hypertrophy, ST segment abnormality, left bundle branch block, right bundle branch block, left axis deviation, atrial fibrillation, T wave abnormality, and Q waves. A total of 107 patients (31%) had postoperative CK MB elevations of trace or greater; 37 had trace, 35 had 1% to 4%, and 35 had greater than or equal to 5% elevation. There was no difference in survival between those with trace and no CK-MB elevation. Patients with increased CK-MB (greater than or equal to 1%) values were more likely to have ECG abnormalities. The following ECG (either preoperative or postoperative) abnormalities were univariately related to decreased postoperative survival: left ventricular hypertrophy (P less than 0.001), ST segment abnormalities (P less than 0.001), left bundle branch block (P less than 0.001), the combination of right bundle branch block and left axis deviation (P = 0.006), Q wave infarction (P less than 0.001), and atrial fibrillation (P less than 0.001). There were 15 in-hospital deaths, and 333 patients were discharged and followed-up for a median of 4.6 years. There were 97 posthospitalization deaths, 61% of which were due to cardiac causes. Overall survival was associated with the degree of CK-MB elevation; the higher the CK-MB, the worse the survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932647 TI - Effects of clonidine on variation of arterial blood pressure and heart rate during carotid artery surgery. AB - The effect of oral premedication with 300 micrograms of clonidine on systemic arterial pressure, heart rate, and plasma norepinephrine levels was assessed in a double-blinded, placebo-controlled study conducted in 29 patients subjected to carotid artery surgery (CAS). Anesthesia was induced with thiopental, 6 mg/kg, and alfentanil, 0.05 mg/kg, and maintained with alfentanil and 0.6% isoflurane in 50% N20/O2. The study was divided into five periods as follows: (1) anesthesia to start of surgery; (2) surgery to carotid artery clamping; (3) carotid artery clamping to unclamping; (4) carotid artery unclamping to the end of surgery; and (5) the first 4 postoperative hours in the recovery room. In the clonidine group (n = 14), plasma norepinephrine concentrations were significantly lower before induction of anesthesia and during the operative period. Heart rate and systemic arterial pressure were lower (P less than 0.01) in the clonidine group at 3 different time intervals (control, carotid clamping, carotid unclamping). However, during each of the previously defined periods, the variability of heart rate and systemic arterial pressure, assessed by the coefficient of variation, was not different between the two groups. The lability of these hemodynamic parameters, expressed as the percentage of values, which increased or decreased more than 20% of control values during the corresponding period, was also comparable between the two groups. The number of patients who experienced at least one episode of hypertension (systolic arterial pressure greater than 180 mm Hg), hypotension (systolic arterial pressure less than 100 mm Hg), or bradycardia less than 45 beats/min was not different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932648 TI - Lidocaine attenuates efferent sympathetic responses to stress in humans. AB - The effects of antiarrhythmic doses of lidocaine on efferent sympathetic outflow or sympathetic responses to autonomic stimuli in humans are unknown. In the present study, direct recordings of postganglionic muscle sympathetic nerve activity (MSNA), which modulates vascular tone, were obtained from the peroneal nerve of 22 healthy volunteers (aged 20 to 27 years). Baseline cardiac intervals (ECG), arterial pressure (radial artery), central venous pressure (CVP, jugular vein), forearm vascular resistance (FVR, Hg-in-Silastic plethysmography), and MSNA were identical in two randomized study groups (lidocaine [L], 1.5 mg/kg bolus, followed by 2 mg/min infusion, n = 12; and placebo [P] saline bolus and infusion, n = 10). Each underwent a cold pressor test (CPT, ice packs to foot for 90 seconds) and baroreceptor test (sequential boluses of 100 micrograms of sodium nitroprusside and 100 micrograms of phenylephrine). Five minutes after the bolus administration of L, plasma L levels were 3 micrograms/mL, which was associated with significant (P less than 0.05) increases in systolic and diastolic pressures (6.6 +/- 2.4 and 5.5 +/- 1.1 mm Hg). This elicited significant reflex decreases in MSNA (-3 +/- 1.1 bursts/100 cardiac cycles) and RR interval (-63 +/- 14 ms). The hypertension, tachycardia, forearm vasoconstriction, and MSNA increase in response to the CPT were significantly attenuated and the sympathoexcitatory response to baroreceptor unloading was blunted by L. These responses were not altered during the administration of P. In the steady-state L infusion period, plasma levels were subtherapeutic (1 microgram/mL) and were insufficient to consistently alter autonomic stress responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932649 TI - Does the preparation of heparin influence anticoagulation during cardiopulmonary bypass? AB - Various preparations of heparin from different manufacturers are commercially available. The influence of bovine lung heparin (BLH) and porcine mucosal heparin (PMH) on anticoagulation and heparin plasma concentration was investigated in four groups of 10 patients undergoing elective aortocoronary bypass grafting either after single dose or repetitive dose (after 60 minutes) of one of these heparin preparations. Heparin plasma concentration increased significantly after injection of heparin (BLH: minimum, 1.67 U/mL; maximum, 2.10 U/mL; PMH: minimum, 1.69 U/mL; maximum, 2.15 U/mL). Sixty minutes after the initial dose, heparin plasma levels were higher in the patients who received PMH. Supplemental heparin doses 60 minutes after the loading dose increased plasma heparin concentration only with porcine mucosal heparin. Elimination of heparin in the urine was not different among the groups. Fibrinogen and antithrombin III concentrations, as well as activated clotting time (ACT; always greater than 400 seconds) and partial thromboplastin time (PTT; always greater than 300 seconds), did not differ among the groups, indicating effective anticoagulation during the bypass period with both types of heparin. It can be concluded that sufficient anticoagulation can be achieved with either kind of heparin. PMH seems to be longer acting and a repeat dose in these patients seems to be necessary only if cardiopulmonary bypass lasts longer than 90 minutes. PMID- 1932650 TI - Blood salvage in cardiac surgery. AB - The aim of this study was to evaluate blood salvage provided by an intraoperative blood recovery system (IBRS) and a mediastinal drainage blood recovery system (MBRS) during and after cardiac surgery. Sixty-six patients undergoing aortocoronary bypass surgery were randomly assigned to three groups of 22 patients each. In group I, patients received only homologous blood (HB). Group II and group III patients received the blood content of the oxygenator after concentration by an IBRS at the end of the operation. In group III, patients also received their own mediastinal drainage blood, shed for 6 hours after operation, after concentration and washing in a MBRS. The patients were transfused with homologous blood if needed, in order to obtain a hematocrit of 28% at the end of operation, 30% the following day, and a hemoglobin level over 10 g/dL while on the cardiac surgery ward (8 to 10 days). The three groups were comparable with respect to age, body surface, preoperative and postoperative hematocrits, number of grafts, bypass duration, and postoperative mediastinal blood loss. The amount of HB that was transfused during the operation was significantly lower in groups II and III than in group I (P less than 0.0001). After the operation it was significantly lower in group II than in group I (P less than 0.05), and in group III versus group I. Thus, 13.6% of patients in group II and 38% of patients in group III did not require HB transfusion. No infection, renal dysfunction, or coagulation disorders were observed. It is concluded that the use of an IBRS allows a significant saving of HB. However, because it does not avoid all HB requirements, it should be associated with other techniques to avoid blood transfusion such as the MBRS or predonation. PMID- 1932651 TI - Priming solutions for cardiopulmonary bypass: comparison of three colloids. AB - The present study was designed to compare the differences in the clinical effects of three colloidal solutions, albumin, urea-linked gelatin, and succinyl-linked gelatin, when used as priming fluids for cardiopulmonary bypass (CPB) under alpha stat conditions. A consecutive series of 105 patients scheduled for cardiac surgery were randomized into three identically managed groups, except for the CPB prime. Variables relating to acid-base status, oncotic activity, metabolism, coagulation, and postoperative evaluation were measured. Marked differences in acid-base status, colloid osmotic pressure, additional prime requirements, blood lactate, urine output, and the need for buffer solutions occurred among groups, with the succinyl-linked gelatin group having better results than the other groups. Changes in hemodynamics, oxygen consumption, and blood-glucose levels during CPB did not vary among groups. There were also no important intergroup differences in hematologic and clotting variables or postoperative parameters such as blood loss or use of blood products. Electrolyte changes were similar except for a significant increase in ionized calcium that occurred in the urea linked gelatin group after bypass. The results indicate that succinyl-linked gelatin is an adequate and safe alternative to human albumin for use as a colloid during CPB under alpha-stat conditions. PMID- 1932652 TI - Biochemical changes induced in the myocardial cell during cardioplegic arrest supplemented with creatine phosphate. AB - The purpose of this work was to evaluate the biochemical changes in the myocardial cell using cardioplegia supplemented with creatine phosphate (CP). Many previous studies have demonstrated the beneficial effect of CP on the ischemic myocardium and its mechanism of action has been assumed to be mainly extracellular. Based on the assumption that CP could also exert some influence on myocardial cellular metabolism, this investigation was carried out. Forty patients undergoing mitral valve replacement were divided into two groups: group 1 was treated with standard cardioplegic solution, and group 2 was treated with cardioplegic solution enriched with CP at a concentration of 10 mmol/L. Samples of papillary muscle, obtained from the removed valve, were studied by means of biochemical methods in order to assess the enzyme activities and the metabolites of the different biochemical pathways related to energy metabolism in the myocardial cell. One papillary muscle sample was used to determine enzyme activities spectrophotometrically; another was used to evaluate metabolite concentrations by spectrophotometric or spectrophotofluorimetric methods. The rate of spontaneous functional recovery after rewarming and weaning from cardiopulmonary bypass (CPB) also was evaluated. In group 2, the Vmax of enzymatic activities was significantly greater (hexokinase, malate dehydrogenase, glutamate dehydrogenase, total NADH cytochrome c reductase) and a better functional state of the heart was observed after CPB. On the basis of the clinical and biochemical data, it is concluded that the myocardium was better preserved when CP was added to the cardioplegic solution. Therefore, the results suggest a possible interaction of exogenous CP with cellular metabolism. PMID- 1932653 TI - Transesophageal echocardiographic diagnosis of left ventricular cavity obliteration causing failure to separate from cardiopulmonary bypass. PMID- 1932654 TI - Reversible pulmonary hypertension secondary to mitral valvular disease as an indication for extracorporeal membrane oxygenation. PMID- 1932655 TI - Detection of myocardial ischemia by transesophageal echocardiography during vein graft repair. PMID- 1932656 TI - Acute myocardial ischemia secondary to interruption of coronary blood flow. PMID- 1932657 TI - Difficult placement of a pulmonary artery catheter prior to coronary artery bypass grafting. PMID- 1932658 TI - Acute right heart failure: pathophysiology, recognition, and pharmacological management. AB - Acute RV failure is an increasingly more common clinical entity and problem. A good understanding of the pathophysiology is required to develop a treatment strategy. Principles of treatment outlined include optimizing RV preload, cautiously reducing RV afterload, and enhancing RV contractility. PMID- 1932659 TI - Case 5--1991. A 44-year-old woman was admitted for elective replacement of the mitral and aortic valves. Could there be another problem? PMID- 1932660 TI - Pro: magnesium is a valuable therapy in the cardiac surgical patient. PMID- 1932661 TI - Con: magnesium is not a valuable therapy in the cardiac surgical patient. PMID- 1932662 TI - Alpha-adrenergic response in patients with ventricular dysfunction. PMID- 1932663 TI - The role of imaging in the non-operative staging of gastrointestinal tumours. PMID- 1932664 TI - Helicobacter pylori infection in children. AB - Helicobacter pylori was sought prospectively by culture of antral biopsy, histology and serology (IgG and IgA) in 440 consecutive endoscopies on children to determine the prevalence, clinical presentation and histological features of H. pylori infection in our population. Twenty-eight patients had H. pylori (8% overall). The mean age of infected patients was significantly higher than that of non-infected patients (P less than 0.0001). No patient under 5 years of age had H. pylori isolated. Overall, there was no significant difference in clinical presentation between those with and those without H. pylori infection, but 23% of patients 5 and 26 years of age who presented with abdominal pain as the indication for their endoscopy had H. pylori isolated. Macroscopic changes ranged from no abnormality to frank ulceration, but the typical antral mamilliform changes were 100% predictive of infection. Fifty-eight per cent of patients with duodenal ulcers, but only 17% with gastric ulcers had H. pylori infection. Histological gastritis was present in 144 patients (including all H. pylori positive patients). None of the patients with another definable cause for gastritis had H. pylori isolated. In conclusion, H. pylori is an important cause of primary gastritis in our population, occurring in children over 5 years of age. Culture of an antral biopsy should be performed in children over this age undergoing endoscopy for the investigation of abdominal pain and, more particularly, in those with peptic ulceration. PMID- 1932665 TI - Intestinal lymphokine-activated killer cells in inflammatory bowel disease. AB - The role of non-specific cytotoxicity in the pathogenesis of inflammatory bowel disease (IBD) was investigated by assaying the natural killer (NK) and lymphokine activated killer (LAK) cell activity of lamina propria mononuclear cells (LPMC) from 22 specimens of intestinal mucosa affected by IBD. Only minimal levels of NK activity were detected against K562 cells, as well as colon carcinoma cells, adenoma cells and fibroblasts freshly isolated from the intestinal mucosa. Culture of LPMC from IBD in the presence of interleukin-2 (IL-2) generated LAK cells that mediated high levels of activity against K562 cells and against neoplastic epithelial cells and fibroblasts derived from the intestinal mucosa. A group of 20 histologically normal specimens of intestinal mucosa showed similar levels of LAK activity against the K562 and intestinal cell targets. The minimal mucosal NK activity in IBD suggests that the cytotoxic properties of NK cells are not important in the pathogenesis of IBD. The presence of LAK precursor cells in the inflamed mucosa of IBD and their ability to lyse biologically relevant targets in vitro suggests that LAK cells have the potential to contribute to intestinal mucosal injury in IBD. PMID- 1932666 TI - Time as a factor in the expression of ethanol injury to the gastric mucosa. AB - A technique of quantitative histology was used to assess the influence of time after injury on the histological expression of gastric mucosal damage. Rats, pretreated with either natural prostaglandin E2 or saline, were subjected to intragastric administration of either 50% or 100% ethanol. Fifteen minutes later the ethanol was removed from the stomach. Rats were sacrificed at either 30 min or 24 h after ethanol instillation. In rats pretreated with saline and subjected to 100% ethanol with or without prostaglandin pretreatment, the extent of deep mucosal damage was markedly underestimated by early evaluation. Only 5.4% of the volume of the gastric mucosa showed evidence of damage at 30 min after ethanol, compared with 57.3% of the volume of the mucosa, at 24 h after 100% ethanol exposure. Assessment of gastric mucosa 24 h after ethanol injury showed that PGE2 reduces the extent of surface area damaged and the volume of the mucosal damage. When 50% ethanol was used as the injurious agent, no difference was noted in the volume of the mucosa damaged when the stomach was assessed at either 30 min or 24 h after injury. These results indicate that full histological expression of injury is not present 30 min after 100% ethanol instillation, at least in part because of fixation of the gastric mucosa by 100% ethanol. Fifty per cent ethanol, which does not cause mucosal fixation, may be better as a test agent. PMID- 1932667 TI - Hepatocyte hepatitis B surface antigen expression in chronic hepatitis B virus carriers in Singapore: correlation with viral replication and liver pathology. AB - The hepatocyte hepatitis B surface antigen (HBsAg) expression in 149 liver biopsies from 124 chronic hepatitis B virus (HBV) carriers was correlated with serum HBV DNA status and histologic activity. Hepatocyte HBsAg was stained by the peroxidase-antiperoxidase method and serum HBV DNA was determined by dot blot hybridization. Sixty-five biopsies (44%) showed minimal changes (MC), 82 biopsies (55%) showed chronic liver disease (CLD) and 2 biopsies (1%) showed hepatocellular carcinoma. Hepatocyte HBsAg was found in 144 biopsies (97%). It was present in the cytoplasm of 141 specimens (95%) and/or plasma membrane of 48 specimens (32%). Approximately half (45%) of the cytoplasmic HBsAg-positive biopsies showed discrete distribution, while the other half (55%) were grouped. Fifty-five per cent (77 of 141) of cytoplasmic HbsAg-positive biopsies had CLD, while 44% (62 of 141) showed MC. There was no relationship between the presence of cytoplasmic HBsAg or its topographic distribution with disease activity. Membrane HBsAg distribution was similar for both groups of patients (MC vs CLD: 25 of 65 (38%) vs 23 of 82 (28%); P = NS). Serum HBV DNA was detected in 98 patients (66%) and was seen mostly in association with CLD (CLD vs MC: 61% vs 39%, P less than 0.001). It was also detected more often in the sera of patients with membrane HBsAg than in those with cytoplasmic HBsAg staining (41 of 48 (85%) vs 97 of 141 (67%); P less than 0.02). However, discrete distribution of cytoplasmic HBsAg was associated with positive serum HBV DNA when compared with grouped distribution (52 of 63 (83%) vs 43 of 78 vs (55%); P less than 0.005). PMID- 1932668 TI - Efficacy of endoscopic sclerotherapy on long-term management of oesophageal varices: a comparative study of results in patients with cirrhosis of the liver, non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal venous obstruction (EHO). AB - A prospective study was conducted to compare the results of long-term endoscopic variceal sclerotherapy in patients with different aetiologies of portal hypertension. A total of 404 consecutive patients were included. There were 234 patients with hepatic cirrhosis, 83 with non-cirrhotic portal fibrosis (NCPF) and 87 with extrahepatic portal venous obstruction (EHO). The mean follow-up for patients with cirrhosis, NCPF and EHO was 25, 37 and 28 months. A total of 73 (31%) patients with cirrhosis, 19 (23%) with NCPF and 10 (11.5%) with EHO rebled (P less than 0.05) on follow-up, prior to eradication of varices. Irrespective of the aetiology, 40 (17%) patients of Child's A class, 42 (33%) of Child's B and 20 (50%) of Child's C class rebled (P less than 0.01). The median bleeding free period (BFP) was longer (P less than 0.05) in patients with EHO than in cirrhotics. Patients in Child's A class had significantly longer BFP than those in Child's B, and the latter had a longer BFP than those in Child's C class (P less than 0.01). The probability of 7-year survival was also better with EHO (97.5%) and NCPF (73.6%) than cirrhotics (41%). Survivals in patients with EHO and NCPF were comparable (P less than 0.1). Similarly 7-year survival irrespective of aetiology in Child's A patients (90.7%) was longer than in Child's B (28.8%), and longer in Child's B than Child's C patients (0%). Success of eradication was greater (P less than 0.05) in EHO (92%) and NCPF (87%) than cirrhotic patients (75%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932669 TI - Comparative effects of 5% ethanolamine oleate versus 5% sodium morrhuate for sclerotherapy of oesophageal varices. AB - Forty-five cirrhotic patients with oesophageal varices were randomized to receive endoscopic injection sclerotherapy with either 5% ethanolamine oleate (EO), or 5% sodium morrhuate (SM). In the EO group, there was a statistically significant higher rate of disappearance of red colour signs on the varices a week after the initial session of sclerotherapy than in the SM group (91.3% vs 45.5%, P less than 0.05). A jet-like bleeding from injection sites at the second session of sclerotherapy occurred in three patients in the SM group and they experienced blurred vision. There was no such occurrence in the EO group. Oesophageal bleeding requiring blood transfusion during the course of repeated sclerotherapy occurred only in the SM group (five patients): bleeding was from a partly thrombosed varix and in four was from oesophageal ulcers. We found that EO administered intravariceally is more efficacious than SM for sclerotherapy of oesophageal varices. PMID- 1932670 TI - A randomized controlled study of low-dose and high-dose terlipressin in the control of acute oesophageal variceal haemorrhage. AB - A randomized controlled trial was designed to investigate whether a high dose of terlipressin could control acute variceal haemorrhage more effectively than a low dose of terlipressin. Forty cirrhotic patients with bleeding oesophageal varices were included, with low-dose terlipressin in 21 patients and high-dose terlipressin in 19 patients. The two groups of patients were similarly matched for all parameters on admission. High-dose terlipressin (84%) seemed to be more effective in the initial control of bleeding than low-dose terlipressin (67%); however this difference was not significant. Complete control of bleeding during 24 h of drug infusion was achieved in 53% of patients receiving high-dose terlipressin and in 48% of those treated with low-dose terlipressin (P greater than 0.05). There were no major complications in either group. Mortality in relation to variceal bleeding and transfusion requirements were similar in the two groups. This study shows that high dose terlipressin is not superior to low dose terlipressin in acute variceal bleeding. PMID- 1932671 TI - Molecular epidemiology of hepatitis B virus in Indonesia. AB - The S-gene sequences of hepatitis B virus (HBV) from 22 carriers in several islands of Indonesia were amplified by polymerase chain reaction, and XbaI-SpeI fragments corresponding to nucleotides 93-529 (437 base pairs) in the S gene were sequenced. The 22 sequences, along with the 5 reported sequences from Indonesia, were compared with each other, and with the corresponding sequences of 20 clones from other countries including China, France, Great Britain, Japan, Kenya, Papua New Guinea, Philippines, USA and USSR. When the 27 HBV DNA clones of various subtypes from Indonesia were classified by the homology in the nucleotide sequence into the five genotypes, twelve belonged to genotype B (subtype adw 7 and ayw 5), 13 to genotype C (adw 1, adr 10, ayr 1 and ar 1), and 2 to genotype D (ayw); none belonged to genotype A or E. Different subtypes of clones in the same genotype indicated that point mutations inducing d-to-y or w-to-r phenotypic changes would be common among Indonesian carriers. Comparison of the translation products of XbaI-SpeI fragments, now available for 47 HBV DNA clones of different genotypes (A 4; B 14; C 21; D 7; E 1), identified several amino acids characteristic to or influenced by the five genotypes as well as those highly conserved by clones of different genotypes. PMID- 1932672 TI - Endotoxin affects the expansion modes of liver macrophages after partial hepatectomy. AB - We studied the effect of increased endotoxin levels on the expansion modes of liver macrophages after two-thirds partial hepatectomy using anti-endotoxin polymyxin B. The expansion consists of dual modes: local proliferation and immigration. Local proliferation of mature cells was evaluated by the S-phase proportion measured by flow cytometric DNA analysis. This proportion (11.8 +/- 1.3% before hepatectomy) decreased to 6.0 +/- 1.1% at 12 h and reached a maximum of 21.9 +/- 2.7% on the 5th day after hepatectomy. In polymyxin B treated rats, the proportion reached a maximum of 21.1 +/- 1.6% at 48 h without any preceding decrease. Immigration of macrophage precursors was evaluated by the decreasing proportion of latex beads-containing cells that were marked as resident liver macrophages by injection of latex beads before hepatectomy. This proportion (98.7 +/- 0.2% before hepatectomy) was significantly decreased to 90.5 +/- 1.6% at 48 h. In polymyxin B treated rats, however, the proportion showed no significant decrease within 3 days. These results indicate that endogenous endotoxin, which suppresses the local proliferation and promotes extrahepatic recruitment, regulates the number of liver macrophages in regenerating rat liver. PMID- 1932673 TI - Alcoholic liver disease in Japanese patients: a comparison with Caucasians. PMID- 1932675 TI - Acid and the pain of non-ulcer dyspepsia. PMID- 1932674 TI - Cholestatic jaundice associated with captopril therapy. AB - Captopril has attained widespread use as an effective agent in the treatment of heart failure and hypertension. Dermatological, renal and haematological toxicity associated with its use has been widely described and is usually well recognized. There have been comparatively few reports implicating it as causing hepatic drug reactions. Most descriptions have emphasized strongly cholestatic features, although a mixed hepatocellular cholestatic picture and predominant hepatocellular reactions have been reported. Between November 1972 and June 1990 only five cases of possible Captopril-associated hepatic dysfunction were reported to the Australian Adverse Drug Reaction Advisory Committee. Cases reported suggest equal sex distribution, latent period to development of abnormality between 1 week and 20 months, with slow resolution of jaundice and biochemical abnormality from 1 week to 6 months after withdrawal of the drug. One case of hepatic coma and death with massive acute hepatic necrosis on biopsy has been reported. Not uncommonly the accompanying systemic features suggest a syndrome of drug hypersensitivity. We report a case of Captopril-induced cholestatic jaundice in which the abnormality occurred 2 weeks after commencement of the drug and resolved slowly upon discontinuation. The case illustrates two important points: first, the importance of taking a full history, obtaining detailed information about previous drug administration in patients admitted with jaundice; and second, in the case of Captopril-induced liver disease, the jaundice may persist for many weeks after drug withdrawal. PMID- 1932676 TI - Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood. PMID- 1932677 TI - Site-directed mutagenesis and expression in Escherichia coli of WMAI-1, a wheat monomeric inhibitor of insect alpha-amylase. AB - The wheat monomeric inhibitor WMAI-1 (syn. 0.28) produced in Escherichia coli using the pT7-7 expression vector has the correct N-terminal sequence and the same electrophoretic mobility and specific activity towards the alpha-amylase from the insect Tenebrio molitor as the native WMAI-1 isolated from wheat. This confirms that the native inhibitor is not glycosylated and contradicts claims that a putative glycosyl moiety was essential for inhibition. Thirteen mutants have been obtained at six different sites. Substitution of the highly conserved N terminal S by the sequence ARIRAR increased the pre-incubation time required for maximum activity. A similar result was obtained by insertion of GPRLPW after position 4, while insertion of EPRAPW at the same position rendered the inhibitor inactive. The substitution D/EGPRL and insertions DGP or D, at position 58, produced complete inactivation. All other mutations had only minor effects on activity. PMID- 1932678 TI - Expression of antifreeze proteins in transgenic plants. AB - The quality of frozen fruits and vegetables can be compromised by the damaging effects of ice crystal growth within the frozen tissue. Antifreeze proteins in the blood of some polar fishes have been shown to inhibit ice recrystallization at low concentrations. In order to determine whether expression of genes of this type confers improved freezing properties to plant tissue, we have produced transgenic tobacco and tomato plants which express genes encoding antifreeze proteins. The afa3 antifreeze gene was expressed at high steady-state mRNA levels in leaves from transformed plants, but we did not detect inhibition of ice recrystallization in tissue extracts. However, both mRNA and fusion proteins were detectable in transgenic tomato tissue containing a chimeric gene encoding a fusion protein truncated staphylococcal protein A and antifreeze protein. Furthermore, ice recrystallization inhibition was detected in this transgenic tissue. PMID- 1932679 TI - Heterozygosity in tetraploid potatoes revealed by rDNA polymorphism analysis of their dihaploid progenies: a contribution to chromosome assignment. AB - Restriction map and organization of rDNA was inferred from analysis of dihaploid progenies of two tetraploid genotypes of cultivated potato. Each tetraploid genotype was characterized by a specific distribution of different types of rDNA repetition units on their four homologous chromosomes II. The genotypes were heterozygous and differed by the kind of units carried by each chromosome II. Models for the generation of the observed organization are discussed and supported by first cloning studies. PMID- 1932680 TI - Purification and cDNA sequencing of an oleate-selective acyl-ACP:sn-glycerol-3 phosphate acyltransferase from pea chloroplasts. AB - The soluble acyl-ACP:sn-glycerol-3-phosphate acyltransferase from chloroplasts of chilling-sensitive and -resistant plants differ in their fatty acid selectivity. Enzymes from resistant plants discriminate against non-fluid palmitic acid and select oleic acid whereas the acyltransferase from sensitive plants accepts both fatty acids. To use this difference for improving plant chilling resistance by biotechnology the gene for an oleate-selective enzyme is required. Therefore, the oleate-selective enzyme from pea seedlings was purified to apparent homogeneity. Tryptic peptides of internal origin were sequenced. Polyclonal antibodies raised in rabbits were used for an immunological screening of a pea leaf cDNA expression library in lambda gt11. A positive clone of 1800 bp was selected showing an open reading frame which codes for 457 amino acids. The deduced amino acid sequence coincides perfectly with the tryptic sequences. A tentative assignment of the processing site was made which divides the preprotein into a mature protein of 41 kDa in accordance with experimental findings and a transit peptide of 88 amino acids. At present the comparison between a selective (pea) and an unselective (squash) acyltransferase sequence does not provide a clue for recognizing the structural differences resulting in different selectivities. PMID- 1932681 TI - Isolation and nucleotide sequence of a cDNA clone encoding the bread wheat (Triticum aestivum L.) CM17 protein. PMID- 1932682 TI - Isoforms of soybean seed oil body membrane protein 24 kDa oleosin are encoded by closely related cDNAs. AB - We have characterized two cDNA clones for 24 kDa soybean oleosin, the seed oil body membrane protein. Differences in the predicted amino acid sequences of the two clones and the presence of a doublet on immunoblots indicate that 24 kDa oleosin exists in at least two isoforms in soybean. The predicted amino acid sequence also contains a unique carboxy terminal region that is dominated by a series of different tandem amino acid repeats. PMID- 1932683 TI - Differential expression of members of the napin storage protein gene family during embryogenesis in Brassica napus. AB - S1 nuclease analysis and sub-family-specific oligonucleotide probes were used to characterize the expression during embryogenesis of the napin storage protein gene family of Brassica napus (oilseed rape). The expression of one sub-class represented by the napin gene gNa peaks and declines earlier than the other members of the family. This sub-class was highly expressed representing ca. 20% of napin mRNA at 26 days after anthesis. PMID- 1932684 TI - Universal primers for amplification of three non-coding regions of chloroplast DNA. AB - Six primers for the amplification of three non-coding regions of chloroplast DNA via the polymerase chain reaction (PCR) have been designed. In order to find out whether these primers were universal, we used them in an attempt to amplify DNA from various plant species. The primers worked for most species tested including algae, bryophytes, pteridophytes, gymnosperms and angiosperms. The fact that they amplify chloroplast DNA non-coding regions over a wide taxonomic range means that these primers may be used to study the population biology (in supplying markers) and evolution (inter- and probably intraspecific phylogenies) of plants. PMID- 1932685 TI - Isolation and characterisation of genes encoding rye prolamins containing a highly repetitive sequence motif. PMID- 1932687 TI - Sugar response element enhances wound response of potato proteinase inhibitor II promoter in transgenic tobacco. AB - The promoter region of the potato proteinase inhibitor II (PI-II) gene was studied to identify cis-acting regulatory sequences involved in sugar response using transgenic tobacco plants. The 5' control region covering an 892 nucleotide sequence upstream from the cap site and a 32 nucleotide untranslated region of the PI-II promoter was able to activate a reporter chloramphenicol acetyltransferase (cat) gene by wounding or by incubating in a sugar-free medium. This wound response was further enhanced by sugar. Hexoses, disaccharides, and some trisaccharides were strong inducers whereas pentoses, deoxy sugars, sugar acids, TCA cycle intermediates, amino acids, and other carbohydrates had little effect on the promoter activity. Deletion of the sequence between -892 and -573 abolished the wound response but not the sugar response. An additional 5' deletion to -453 removed the sugar inducibility. Locations of the cis-acting regulatory elements were further elucidated by 3' deletion analysis. Deletion of the downstream region from -520 did not affect the wound or sugar response of the promoter. However, 3' deletion mutant -574 was unable to respond to sugar but did respond weakly to wounding. Further deletion to -624 abolished both responses. Therefore, it can be concluded that a wound response element is located in between -624 and -574 and that the response is further enhanced by a sugar response element located in the sequence between -573 and -520. PMID- 1932686 TI - Expression of photosynthesis genes in the cyanobacterium Synechocystis sp. PCC 6803: psaA-psaB and psbA transcripts accumulate in dark-grown cells. AB - We have cloned and sequenced the psaA and psaB genes from the unicellular cyanobacterium Synechocystis sp. PCC 6803. These genes are arranged in tandem, are co-transcribed, and are highly homologous to the psaA and psaB genes previously characterized. RNA was isolated from light-grown cells, from cells put in total darkness with and without glucose, and from cells grown under light activated heterotrophic growth (LAHG) conditions. Quantitation of hybridization to northern blots revealed only a slight decrease in the accumulation of the psaA psaB transcript in cells grown in complete darkness with glucose and in LAHG cells, relative to light-grown cells. Accumulation of the psbA transcript steadily declines through dark incubation, with a steady-state level in LAHG cells 28% of that in light-grown cells. Transcripts from psbD, psaD, and rbcLS accumulate in cells grown in complete darkness and in LAHG cells to approximately the same levels as in light-grown cells. Photosynthesis gene transcripts in cells grown in the dark without glucose were detected, but were highly degraded. Our data prove that transcripts from photosynthesis genes do accumulate in dark-grown Synechocystis 6803, which may allow for synthesis and assembly of photosystem (PS) I and PS II in the dark. PMID- 1932688 TI - Regulation of the maize rab17 gene promoter in transgenic heterologous systems. AB - The maize rab17 gene is expressed in different plant parts in response to ABA and osmotic stress (J. Vilardell et al., Plant Mol Biol 14 (1990) 423-432). Here we demonstrate that 5' upstream sequences of the rab17 gene confer the appropriate patterns of expression on the chloramphenicol acetyl transferase (CAT) reporter gene in transgenic tobacco plants, as well as in protoplasts derived from cultured rice cells. Specifically, a CAT construct containing a large 5' upstream fragment of rab17 (-1330/+29) results in high levels of CAT activity in embryos, leaves and roots of transgenic plants subjected to water stress or ABA treatment. Transient expression assays in rice protoplasts transfected with CAT genes fused to rab17 promoter deletions indicate that a 300 bp DNA fragment (-351/-102) is sufficient to confer ABA responsiveness upon the reporter gene. Furthermore, a 100 bp sequence (-219/-102) is capable of conferring ABA responsiveness upon a minimal promoter derived from the 35S CaMV promoter. Gel retardation experiments indicate that maize nuclear proteins bind to this fragment. This region of 100 bp contains a sequence (ACGTGGC) which has been identified as an abscisic acid response element in studies of other ABA-responsive plant genes. PMID- 1932689 TI - Differential induction of acquired resistance and PR gene expression in tobacco by virus infection, ethephon treatment, UV light and wounding. AB - Genes for acidic, extracellular and basic, intracellular pathogenesis-related (PR) proteins of tobacco were studied for their response to tobacco mosaic virus (TMV) infection, ethephon treatment, wounding and UV light. The genes encoding the acidic PR proteins (PR-1, PR-2, PR-3, PR-4 and PR-5) responded similarly to the different forms of stress. They appeared to be highly inducible by TMV, moderately inducible by ethephon treatment and UV light and not inducible by wounding. The genes for the basic counterparts of PR-1, PR-2, PR-3 and PR-5 also displayed a common stress response. However, this response was different from that of the acidic PR proteins. Here, the highest induction was obtained upon ethephon treatment, while the other stress conditions resulted in somewhat lower levels of expression. Most genes for acidic PR proteins are systemically induced in the uninfected upper leaves of TMV-infected plants, whereas the genes encoding the basic PR proteins are not. Increased levels of resistance to TMV, comparable to resistance obtained by pre-infection with the virus, were found in UV irradiated leaves but not in wounded or ethephon-treated leaves. This indicates that the basic PR proteins are not involved in resistance to TMV infection. Tobacco phenylalanine ammonia-lyase genes were not inducible by the various stress conditions. The implications of these findings in relation to the phenomenon of acquired resistance are discussed. PMID- 1932690 TI - Expression and stability of amplified genes encoding 5-enolpyruvylshikimate-3 phosphate synthase in glyphosate-tolerant tobacco cells. AB - Two distinct cDNAs for 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) were obtained from a glyphosate-tolerant tobacco cell line. The cDNAs were 89% identical and the predicted sequences of the mature proteins were greater than 83% identical with EPSPS proteins from other plants. Tobacco EPSPS proteins were more similar to those from tomato and petunia than Arabidopsis. One cDNA clone, EPSPS-1, represented a gene that was amplified in glyphosate-tolerant cells, while the gene for EPSPS-2 was unaltered in these cells. Consequently, EPSPS-1 mRNA was more abundant in tolerant than unselected cells, whereas EPSPS-2 mRNA was at relatively constant levels in these cell lines. Exposure of unselected cells and tobacco leaves to glyphosate produced a transient increase in EPSPS mRNA. However, glyphosate-tolerant cells containing amplified copies of EPSPS genes did not show a similar response following exposure to glyphosate. A significant proportion of the EPSPS gene amplification was maintained when tolerant cells were grown in the absence of glyphosate for eight months. Plants regenerated from these cells also contained amplified EPSPS genes. PMID- 1932691 TI - A detailed study of the regulation and evolution of the two classes of patatin genes in Solanum tuberosum L. AB - The class-specific expression of patatin genes was investigated by analysing four new patatin genes. A class I patatin gene from cv. Berolina as well as a class I and two class II patatin genes from the monohaploid cultivar AM 80/5793 were isolated and partially sequenced. Sequence comparison indicates rearrangements as the major source for the generation of diversity between the different members of the classes. The expression of single genes was studied in potato plants transformed with chimaeric genes where the putative patatin promoters were fused to the GUS reporter gene. A detailed histochemical analysis reveals that both class I genes are expressed as the previously described class I patatin gene B33 from cv. Berolina [1], i.e. in the starch-containing cells of potato tubers and in sucrose-induced leaves. The class II gene pgT12 shows the same pattern as the previously described class II gene pgT2 [2], i.e. expression in root tips and in the vascular tissue of tubers, whereas no activity was detectable for pgT4. Thus the expression pattern of both classes of genes seems to be stable at least within or even between different cultivars. PMID- 1932692 TI - Characterization of pollen polygalacturonase encoded by several cDNA clones in maize. AB - A full-length cDNA clone, named PG1, abundantly expressed in late stages of pollen development, has been isolated from a cDNA library using a differential screening method with cDNA probes representative of microspores at early or late developmental stages. The encoded 410 amino acid polypeptide has significant homology with various polygalacturonases (PG) described elsewhere. Two polypeptides, of 49 and 53 kDa respectively, have been identified in the active PG fraction, isolated from mature pollen by immuno-cross-reaction with tomato PG antibodies. According to their N-terminal sequence, they can be identified as being mature peptides encoded by the PG1 cDNA clone. We propose that these two proteins derive from a unique precursor through several post-translational events, including the excision of a 22 amino-terminal signal peptide and glycosylation. PG-encoding genes from a small genomic family. Sequence analysis of three PG cDNA clones shows that they are closely related. The divergence of nucleotides between these three cDNA clones is 1%. They encode the same product. PMID- 1932693 TI - Oligonucleotide-directed mutagenesis of psbB, the gene encoding CP47, employing a deletion mutant strain of the cyanobacterium Synechocystis sp. PCC 6803. AB - A mutant strain of the cyanobacterium Synechocystis sp. PCC (Pasteur Culture Collection) 6803 has been developed in which psbB, the gene coding for the chlorophyl alpha-binding protein CP47 in Photosystem II (PSII), has been deleted. This deletion mutant can be used for the reintroduction of modified psbB into the cyanobacterium. To study the role of a large hydrophilic region in CP47, presumably located on the lumenal side of the thylakoid membrane between the fifth and sixth membrane-spanning regions, specific deletions have been introduced in psbB coding for regions within this domain. One psbB mutation leads to deletion of Gly-351 to Thr-365 in CP47, another psbB mutation was targeted towards deletion of Arg-384 to Val-392 in this protein. The deletion from Gly-351 to Thr-365 results in a loss of PSII activity and of photoautotrophic growth of the mutant, but the deletion between Arg-384 and Val-392 retains PSII activity and the ability to grow photoautotrophically. The mutant strain with the deletion from Gly-351 to Thr-365 does not assemble a stable PSII reaction center complex in its thylakoid membranes, and exhibits diminished levels of CP47 and of the reaction center proteins D1 and D2. In contrast to the Arg-384 to Val-392 portion of this domain, the region between Gly-351 and Thr-365 appears essential for the normal structure and function of photosystem II. PMID- 1932694 TI - cDNA cloning, sequence analysis and seasonal expression of lignin-bispecific caffeic acid/5-hydroxyferulic acid O-methyltransferase of aspen. AB - A cDNA clone (Ptomt 1) encoding a lignin-bispecific O-methyltransferase (OMT) was isolated by immunological screening of a lambda gt11 expression library prepared from mRNA of developing secondary xylem of aspen (Populus tremuloides). Nucleotide sequence analysis of Ptomt1 revealed an open reading frame of 1095 bp which encodes a polypeptide with a predicted molecular weight of 39,802, corresponding well with the size of the OMT polypeptide estimated by SDS-PAGE. Authenticity of Ptomt1 was demonstrated in part by detection of OMT activity and protein in extracts of Escherichia coli cultures transformed with a plasmid construct containing Ptomt1. In addition, peptides produced from a proteolytic digest of purified OMT and sequenced by automated Edman degradation matched to portions of the deduced amino acid sequence of Ptomt1. Comparison of this sequence to amino acid sequences of OMTs of diverse species identified regions of similarity which probably contribute to the binding site of S-adenosyl-L methionine. Tissue-specific expression was demonstrated by northern analysis which showed that Ptomt1 hybridized to a 1.7 kb transcript from aspen developing secondary xylem and by tissue printing of aspen stems in which only the outer layer of xylem bound the antibody. A biphasic pattern of gene expression and enzyme activity for OMT was observed from xylem samples of aspen during the growing season which suggests linkage between gene expression for a monolignol biosynthetic enzyme and seasonal regulation of xylem differentiation in woody plants. PMID- 1932695 TI - Amber codon suppression: the in vivo and in vitro analysis of two C-hordein genes from barley. AB - A 1420 bp genomic fragment (lambda-hor1-17) encompassing a Hor-1 gene encoding a C-hordein polypeptide is presented. The deduced amino acid sequence is 261 residues long. It comprises a 20 amino acid signal peptide, unique NH2- and COOH terminal regions and a coding region comprised of pentapeptide (PQQPY) and octapeptide (PQQPFPQQ) repeat motifs. The 431 bp of 5' non-coding region contains a 'TATA box' at -105, a 'CACA box' (-181 to -201) and a -300 prolamin element. In the 3' non-coding region there are two putative polyadenylation signals located 88 and 142 bp downstream of the stop codon. The structure of lambda-hor1-17 is compared with that of another gene (lambda-hor1-14) encoding a C-hordein polypeptide, which contains an amber codon interrupting the ORF. A functional assay in which the 5' non-coding regions of the two genes were fused to the beta glucuronidase (GUS) gene demonstrated that both genes were transcriptionally active and that circa 430 bp of the C-hordein promoters were sufficient to drive the expression of the GUS gene in developing barley endosperms. It also demonstrated that both promoters had transcriptional efficiencies comparable with that of the 35S CaMV promoter. The in vitro translation of the coding region of lambda-hor1-14 in the wheat germ system showed that the premature stop codon could be partially suppressed. The suppression was also demonstrated in a transient expression assay in vivo using isolated barley endosperms. PMID- 1932696 TI - The full precursor of the 33 kDa oxygen-evolving complex protein of wheat is exported by Escherichia coli and processed to the mature size. AB - A full-length cDNA encoding the precursor of the lumenal 33 kDa oxygen-evolving complex protein from wheat was inserted into a prokaryotic expression vector. Cell-free transcription-translation of this construct generates a precursor protein of the correct size. However, when expressed in Escherichia coli, the protein is quantitatively exported into the periplasm and processed to the mature size. The results indicate that the thylakoid transfer sequence of this precursor can function as an internal E. coli export signal. PMID- 1932697 TI - Cloning and characterization of a carrot hsp70 gene. PMID- 1932698 TI - Nucleotide sequence of cDNA clones encoding PSI-D2 protein of photosystem I in Nicotiana sylvestris. PMID- 1932699 TI - Characterization of the maize pyruvate decarboxylase gene. PMID- 1932700 TI - Isolation and characterization of a pea catalase cDNA. PMID- 1932701 TI - Isolation and sequence analysis of a cDNA that encodes pea manganese superoxide dismutase. PMID- 1932702 TI - Sequence of an rbcS gene from cotton. PMID- 1932703 TI - MHC-antigen-T cell interactions: an overview. AB - We describe the establishment and validation, both at the biochemical and biological levels, of direct assays to measure the interactions between synthetic peptides and purified HLA class II molecules. The results of several independent approaches to define the structural requirements for the interaction of peptide class II molecules are also described. Such approaches include random screening, sequence analysis, and site-directed mutagenesis. Finally, in vivo data illustrating the possibility that the competition at the level of the interactions between autoantigenic peptides and class II molecules could be a useful tool in the treatment of T cell-mediated autoimmune diseases are presented. PMID- 1932704 TI - Antigenic peptide interaction with MHC molecules: implications for the design of artificial vaccines. AB - Both helper and cytotoxic T cells see primarily a limited number of immunodominant sites on a protein. The reasons for immunodominance are many. We have explored primarily the roles of antigen processing and binding to histocompatibility molecules, as well as the structural features of the antigenic peptide. This information has led to the identification and characterization of sites stimulating helper or cytotoxic T cells specific for antigens from malaria or HIV, and ways to couple and immunize with these, that may be useful for vaccine development. We also observed a striking concordance between helper and cytotoxic T cell sites. PMID- 1932705 TI - Inhibition of T cell activation by blockade of MHC class II molecules. AB - Autoimmune diseases result from the activation of self-reactive T cells induced by autoantigens or by foreign antigens cross-reactive with an autoantigen. A striking characteristic of autoimmune diseases is the increased frequency of certain HLA alleles in affected individuals. Moreover, as demonstrated for example in rheumatoid arthritis and insulin-dependent diabetes mellitus, class II alleles positively associated with autoimmune diseases share amino acid residues in the hypervariable HLA regions involved in peptide binding. Therefore, it is likely that disease-associated HLA class II molecules have the capacity to bind the autoantigen and present it to T cells, thereby inducing and maintaining, under appropriate conditions, the autoimmune disease. The data reviewed here demonstrate MHC-selective inhibition of antigen-induced T cell responses in vivo by parenterally administered soluble, MHC-binding peptide competitors, under conditions in which the competitor is not immunogenic. This suggests the feasibility of a therapeutic approach based on MHC blockade in the treatment of HLA-linked autoimmune diseases. PMID- 1932707 TI - Protein kinase C activation in human ventricular myocardium. AB - We investigated the effects of 12-deoxyphorbol 13 isobutyrate 20 acetate (DPBA) on contractile function and intracellular calcium handling in normal human ventricular myocardium. The activation of protein kinase C by DPBA resulted in a decrease in sarcoplasmic reticulum calcium release and a reduction in isometric twitch. Force-Calcium relationships were obtained by tetanizing intact muscles or by chemically skinning muscle fibers. These relationships were fitted to a modified Hill function. In intact preparations, DPBA shifted the force-calcium relationship towards higher intracellular calcium concentrations by 0.12 microM (n = 5) and maximal force production was decreased 45.5 +/- 6.1%. These experiments show that protein kinase C activation affects intracellular calcium availability and myofibrillar calcium responsiveness. PMID- 1932706 TI - A modelized distribution of actomyosin interactions in the vertebrate cardiac muscle. AB - Preliminary assumption of this model is that interactions between actin and myosin presupposes an exact three-dimensional geometrical correspondence between sites, due to the very short time constants present under physiological conditions. Only small and controlled torsions of the actin filaments are accepted. The model uses geometrical information concerning orientations and dimensions of myosin crossbridges and actin monomeres to modelize the distribution of their inter-actions. An orientation map of actin sites in the cross-section perpendicular to the filament axis is proposed, adapted to the specific filament array of vertebrate muscle. Orientation of myosin crossbridges follows Luther's rules. According to the model, any interaction between actin and myosin implies the superimposition of their respective cross-sectional planes. The axial length of actin monomere is 55 A; the distance between two crossbridges along the myosin filament axis is 143 A. The following properties are derived: 1) The shortening step of the sliding actin filament must be a multiple of 11 A (highest common factor). Taking into account the staggered disposition of the two actin strands and the presence of two heads for each cross-bridge, the most probable value for this shortening step is equal to 99 A. A specific scheme is proposed to describe the shortening process. The behavior of the modelized crossbridge does not need any elastic structure--2) Planes situated at 715 A (lowest common multiple) of actin and myosin coinciding planes are also in coincidence. In a hemi-sarcomere the maximal number of these planes, referred to as simultaneously activable planes, is 10 (20 if both myosin heads are considered). The proportion of interactions authorized by the site orientations is 1/12. In the model, the concept of randomly recruited crossbridges is replaced by a discretized recruitment, based on geometrical properties at an ultrastructural level. The proposed distribution is homogeneous: it can be extended radially in the sarcomere and authorizes the actin filament sliding in the whole physiological range under the control of a dual activation function, reproducing Ca++ temporal and spatial distribution. PMID- 1932708 TI - Rheology of myocardium. The relation between force, velocity, sarcomere length and activation in rat cardiac muscle. AB - The relations between force, shortening velocity and sarcomere length (F-V-SL) during cardiac contraction, underlie Starling's Law of the Heart. F-V-SL were investigated in isolated, intact and skinned trabeculae and myocytes from rat heart. SL and V were measured with laser diffraction techniques; F was measured with a silicon strain gauge. The "ascending" F-SL relation appeared to result from both length dependent sensitivity of the contractile system to activator calcium ions and the presence of restoring forces (Fr), residing in the collagen skeleton of the muscle. Fr increased exponentially with decreasing SL below slack length to 25% of maximal twitch force (Ft) at SL = 1.60 microns. V was inversely proportional to the load and attained a maximum at zero load (Vo). Vo increased with factors that increased F: [Ca++], SL, and time during the twitch. Vo reached a maximum and remained constant (13.5 microns/s) when F attained or exceeded 50% of its maximum value. Viscous force in the passive muscle increased with V to a maximum of 4% of Ft at V = 40 microns/s. The relation between Vo and these factors could be predicted by a model of contraction in which the measured visco elastic properties of myocardium were incorporated, while the truly unloaded maximal velocity of sarcomere shortening was assumed to be independent of the level of activation of the contractile filaments. A model of the cardiac cycle which explains the relation between Frank's and Starling's laws is presented. PMID- 1932709 TI - Prediction of the cardiac muscle force-velocity relation from its force-time and force-length relations. AB - The force-velocity relation for cardiac muscle fibers can be calculated from a proposed constitutive law based on force-time and force-length data. The calculated force-velocity relation agrees quite well with the measured force velocity relation obtained from a quick release of sarcomere controlled rat cardiac trabeculae. The theory confirms the measured linear relationship between maximal velocity of sarcomere shortening and sarcomere length. The implication is that the force-velocity relation is not an independent property, and therefore need not be explicitly included as a rheological element in the constitutive law. PMID- 1932711 TI - Measurements of compression of Ehrlich ascites tumor cells and their relevance to hematogenous metastasis. AB - Ehrlich ascites cancer cells were compressed between glass microscope slides by the addition of weights. The projected areas of the cells were measured, and their surface membrane integrity determined by means of trypan-blue exclusion tests under different compression loads of 0 to 800g. The results are compatible with a two-step mechanism for surface rupture; first the cell membrane is unfolded and then stretched, with modest degrees of stretching associated with membrane rupture. It is calculated that lethal surface membrane rupture of the type produced here by compression, could also be produced when cancer cells are deformed by entry and passage along relatively non-deformable capillaries. This would at least partially account for the rapid destruction of cancer cells in the microcirculation. The observation that isolated nuclei are less deformable than whole cells, may indicate that their nuclei may protect cancer cells from biomechanical trauma. PMID- 1932710 TI - Effects of gender and age on thixotropic properties of whole blood from healthy adult subjects. AB - The thixotropic parameters of whole blood from 314 healthy subjects (154 women, 160 men) were measured with our modified method by Low shear 30 Rheometer and calculated according Huang's equation. This communication offered the reference range of thixotropic parameters from man and woman group. The results demonstrated that no significant differences existed in the plasma viscosity and fibrinogen between man and woman group. Man group had statistically higher values in HCT, yield stress (tau 0), Newtonian contribution of viscosity (mu), non Newtonian contribution of viscosity (eta s--mu), apparent viscosity at 2.37 sec-1 (eta s), the equilibrium value of the structural parameter (A) and apparent kinetic rate constant of rouleaux breakdown (ARC) than those in woman group. The man and woman groups could be separately divided into five subgroups in terms of age. It was found that the levels of fibrinogen and plasma viscosity had a tendency of increasing with aging. In the old subgroup (greater than 60 years) of men and women HCT, tau v, mu, eta s, (eta s--mu) and A had significant lower values than those in young and middle-age subgroups. However, it was very interested that there were differences of ARC versus age between man group and woman group, i.e. ARC in the man subgroup II, IV had lower and the woman subgroup II, III, IV had higher values than their respective older subgroup did. PMID- 1932712 TI - The effects of shear stress and metastatic phenotype on the detachment of transformed cells. AB - A parallel-plate flow chamber was used to quantify the detachment of normal, transformed, and reverted rat fibroblasts from a confluent monolayer of normal fibroblasts. In this method, known shear stresses were applied to the adherent cells and the percent of cells detached from the monolayer was determined. Results indicate that the detachment of all cell types increased with increasing shear stress and detachment of highly metastatic ras-transformed cells was significantly higher than that of either nonmetastatic normal cells or transformed cells reverted with the Kirsten ras revertant (K-rev 1a) gene, which are lowly metastatic. From these results, it is concluded that a correlation exists between the metastatic phenotype of the cell and its ability to detach from normal cells. PMID- 1932713 TI - Generalized dispersion in a synovial fluid of human joints. AB - An unsteady convective diffusion in a synovial fluid of human joints modeled as a power-law fluid is studied using the generalized dispersion model of Gill and Sankara-subramanian [12]. The contributions of convection and diffusion, and pure convection on the dispersion of nutrient are investigated in detail. It is shown that the effect of decrease in non-Newtonian parameter is to decrease the dispersion coefficient. The mean concentration distribution appears to increase as the non-Newtonian parameter decreases upto a certain value of the axial distance. Beyond this point, however, the reverse pattern is observed. PMID- 1932714 TI - Reduction of the surface-volume ratio: a physical mechanism contributing to the loss of red cell deformability in malaria. AB - Plasmodia and other intraerythrocytic parasites reduce the deformability of the red cells they infect. One mechanism potentially responsible for this reduction in deformability is the decrease in the surface:volume (S/V) ratio of the red cell which occurs with parasite growth. To examine this hypothesis, normal red cells were allowed to phagocytize polylysine-coated latex spheres 1.0 to 2.9 microns in diameter. Deformability decreased progressively with spheres of increasing size, consistent with the decreasing S/V ratios of those cells (from an initial length:width [L/W] ratio of 2.398 +/- 0.549 for normal red cells to 1.559 +/- 0.249 for red cells containing 2.92 microns latex spheres at 40 dynes per cm2, p less than 0.001). Nevertheless, red cells containing latex spheres 2.0 2.9 microns in diameter remained deformable and continued to tank tread, in contrast to red cells containing Plasmodium falciparum parasites of that size, which are not deformable and do not tank tread. The progressive decrease in S/V produced by the latex spheres is consistent with their effect on the L/W ratio. However, the total loss of deformability observed with red cells containing parasites of similar or smaller size cannot be explained on these grounds alone. It suggests an additional mechanism, such as calcium-induced crosslinking of the red cell cytoskeleton. PMID- 1932715 TI - Red cell mechanics: what changes are needed to adversely affect in vivo circulation. AB - The ability of red cells to deform is essential to allow their circulation. However the degree of rheological abnormality which can be tolerated before flow is impaired is not so clear. Red cell rheology has been characterised in a number of physiological, pathological and genetic conditions, and some inferences can be drawn. In vivo aging causes a small loss of cell deformability attributable to increased membrane and internal viscosity; volume and surface area are also lost. These changes cannot be sufficient to cause cellular removal, since the cells sampled had continued to circulate. In sickle cell disease, the oxygenated blood contains dense cells that are more severely abnormal than dense, aged cells from normal individuals. Melanesian ovalocytes have comparable rigidity to dense SS cells, but this condition has no marked circulatory pathology. Thus circulatory problems in SS disease probably stem from deoxygenation-induced sickling which causes extreme loss of deformability, rather than from the abnormal cells in oxygenated blood. In falciparum malaria, immature parasites cause appreciable loss of deformability but continue to circulate. Maturation of the parasites causes much greater rheological changes, including attachment to vascular endothelium, and the cells cease to circulate. In summary, quite marked changes in cell mechanics can occur without loss of ability to circulate. It thus seems that slight rheological alterations reported in some clinical studies are unlikely to cause appreciable flow disruption. PMID- 1932716 TI - Effects of the non-Newtonian viscosity of blood on flows in a diseased arterial vessel. Part 1: Steady flows. AB - Effects of the non-Newtonian viscosity of blood on a flow in a coronary arterial casting of man were studied numerically using a finite element method. Various constitutive models were examined to model the non-Newtonian viscosity of blood and their model constants were summarized. A method to incorporate the non Newtonian viscosity of blood was introduced so that the viscosity could be calculated locally. The pressure drop, wall shear stress and velocity profiles for the case of blood viscosity were compared for the case of Newtonian viscosity (0.0345 poise). The effect of the non-Newtonian viscosity of blood on the overall pressure drop across the arterial casting was found to be significant at a flow of the Reynolds number of 100 or less. Also in the region of flow separation or recirculation, the non-Newtonian viscosity of blood yields larger wall shear stress than the Newtonian case. The origin of the non-Newtonian viscosity of blood was discussed in relation to the viscoelasticity and yield stress of blood. PMID- 1932717 TI - Rheological measurement of blood coagulation in vascular vessel model tube consisting of endothelial cells monolayer. AB - An in vitro experimental system was developed to study the interaction between endothelial cells and blood as an early event in coagulation. A designed vascular vessel model tube is composed of a monolayer of bovine aorta endothelial cells (BAECs) cultured on an inner surface of a glass tube by means of a rotatory cultivation method. The change of fluidity during coagulation of blood in the tube was measured by a rheological technique. The rate of coagulation of blood in contact with endothelial cells was affected by cell culture conditions such as cell age, passage number of BAECs and substrate beneath endothelial cells. Fibrinolytic activity of the cells was examined by the rheological method. The present experimental system would be useful in examining the mechanism of blood coagulation based on the interaction between blood and endothelial cells as well as in evaluating endothelial cell functions. PMID- 1932718 TI - Propagation properties of vasomotion at terminal arterioles and precapillaries in the rabbit mesentery. AB - A vasomotion activity in the mesentery of anesthetized rabbits were studied by simultaneous measurements of inside diameters at multiple sites in arterioles, precapillaries and their bifurcations. A frame-by-frame diameter determination technique was used with a microcomputer-assisted laser video disk recorder and video-image analysis system. Simultaneous intensity profiles across microvessels were continuously obtained. Applying an automatic wall surface tracer and a graphic editor to construct temporal sequences of intensity profiles, we obtained digitized data of inside diameters of microvessels, and implemented cross correlation analysis between data sets to calculate phase differences of vasomotion at separated sites. The present analysis of the propagation of vasomotion showed that the vasomotion originated from the orifice of precapillaries at the bifurcations, spreading downstream in the precapillary. The vasomotion wave spreads both upstream and downstream along single arterioles from various origins of the vasomotion activity. The propagation velocity of vasomotion was 0.17 +/- 0.03 mm/sec (n = 19), and it became significantly slower through the branching points than along the arterioles. It is suggested that the vasomotion in terminal arterioles and precapillaries may spread through some mechanical transmission factors. PMID- 1932719 TI - Viscoelastic properties of transformed cells: role in tumor cell progression and metastasis formation. AB - The micropipette aspiration technique was used to investigate the deformation properties of a panel of nontransformed and transformed rat fibroblasts derived from the same normal cell line. In this method, a step negative pressure is applied to the cell via a micropipette and the aspiration distance into the pipette as a function of time is determined using video techniques. A standard solid viscoelastic model was then used to analyze the viscoelastic properties of the cell. From these results, it is concluded that a direct correlation exists between an increase in deformability and progression of the transformed phenotype from a nontumorigenic cell line into a tumorigenic, metastatic cell line. PMID- 1932720 TI - Microvessel diameter estimation: error bias correction of serial measurements. AB - The assessment of vessel patency can be substantially improved by serial microvessel diameter measurements taken successively along an extensive length of the vessel. It is possible to avoid making the a priori assumptions about the existence or location of local constriction sites implicit in single diameter measurements. The problem then becomes one of making sense of tens or hundreds of measurements for each vessel. Equivalent diameter is defined here as as the diameter of a uniform circular cylinder of the same length as the original vessel, and having the same total resistance. Direct computation of the equivalent diameter, without taking measurement errors into account, leads to an underestimation of the true equivalent diameter even if the individual diameter measurements were not biased. We have developed a method for effectively eliminating this bias. It has been applied to serial microvessel diameter measurements of the guinea pig cochlea, automatically measured using an image analysis system. In this report, the results were developed for diameter estimates with an approximate gaussian distribution; however the method is readily extended to other error distributions. Convergence of the bias compensation was rapid. Use of the new method is advisable with as few as three diameter estimates per vessel. PMID- 1932721 TI - Multiangle visualization of flow patterns in saccular aneurysms. PMID- 1932723 TI - [Magnetic resonance tomography in the assessment of anterior cruciate ligament reconstruction by tendon grafts]. AB - 150 patients were examined via magnetic resonance (MR) after anterior cruciate (ACL) ligament reconstruction (76 patellar tendon grafts, 53 semitendinous tendon grafts and 21 sutures). The results of MR were compared with clinical tests (Lachman, pivot-shift and anterior drawer test), in 2 cases with the operative findings, and in one case with arthroscopy findings. In 91% of patients with a clinically stable knee we found a continuous low-intensity ligamental structure. 10 patients were examined twice or more between 8 days and 6 months after surgery. Ligamental structures of low signal intensity did not significantly change their MR characteristics. MR is a valuable noninvasive method for evaluating ligament reconstructions. PMID- 1932722 TI - [MR tomography of aneurysmal bone cyst]. AB - The preoperative findings of magnetic resonance imaging (MRI) in six histology proven aneurysmal bone cysts (ABC) are examined and compared with previous publications concerning MRI of ABC. The signal intensities differ considerably, and not all of our cases conform with the literature data. They can be summarised in three different subheadings: one form that is very inhomogeneous in T1- and T2 weighting, with fluid-fluid levels in the cystic spaces; one intermediate form without fluid-fluid levels, which is inhomogeneous only in T2-weighted images; and finally, an unusual form of ABC that has homogeneous low signal both in T1- and T2-weighting, and which has not been described in literature so far. PMID- 1932724 TI - [CT arthrography of the shoulder after surgical repair for ventral instability]. AB - 25 patients who had undergone a modified Lange repair were examined postoperatively after about four years, both clinically and by CT arthrography. Ventral redislocation was no longer seen postoperatively. As regards residual ventral instability, there was agreement between CT arthrography and the clinical findings in 20/25 patients (90%). Newly developed or residual dorsal instability could be accurately demonstrated by the presence of pathological changes of the dorsal labrum and by the observation of a wide dorsal joint recess. CT arthrography did not provide reliable evidence concerning loss of function and mobility of the treated shoulder. However, the presence of marked capsular folding suggests a poor clinical result. PMID- 1932725 TI - [Cervical lymph node metastasis: significance of computerized tomography and palpation. A histologically controlled comparison]. AB - Palpation and CT are used before treatment, in addition to sonography, in patients with tumours in the head and neck for lymph node staging. The accuracy of CT in identifying lymph node metastases is 79% and in our clinical material is similar to the accuracy of palpation (81%). Sensitivity of CT (93%) is better than palpation (82%). Specificity of CT (65%) is less than that of palpation (82%). The high percentage of false positives from CT (35%) is due to enlargement of the lymph nodes resulting from sinus histiocytosis or follicular hyperplasia. CT is significantly superior to palpation in demonstrating the relationship of the lymph nodes to the surrounding tissues (vessels, muscles, bones). PMID- 1932727 TI - [High-resolution CT of the lung versus thoracic radiography after adjuvant radiotherapy in breast carcinoma]. AB - We examined the lungs of 35 women following postoperative radiotherapy for breast cancer by using high-resolution computed tomography (HR-CT). Radiotherapy was performed on a cobalt 60 unit using a five-field technique. The average interval between the end of radiotherapy and HR-CT examinations was 23.8 months. HR-CT was limited to those lung areas that were at risk for radiation-induced changes. In 40% of patients minimal interstitial damage (e.g. thickened septal lines, curvilinear densities) invisible on chest x-ray was demonstrated by HR-CT. Massive fibrosis as reported by others was not seen in our study. We conclude that in case lung involvement is suspected clinically during or after radiotherapy, HR-CT is the method of choice for demonstrating these morphological changes. PMID- 1932726 TI - [Lymphographic findings in AIDS patients]. AB - The lymphographic findings in 20 patients with AIDS-most in clinical stage IV-can be divided into four categories. In six there were no specific changes and in a further six the storage pattern was that of sinus histiocytosis. One patient showed transition to malignant lymphoma and another patient had atypical mycobacterial infection of the retroperitoneal lymph nodes. Six patients showed a lymphographic pattern of scarring. The results of this study show that lymphography is a sensitive method that can provide important additional information. PMID- 1932728 TI - [Value of supine thoracic radiography in the diagnosis and quantification of pleural effusions: comparison with sonography]. AB - The purpose of this prospective study was to verify the value of the supine chest radiograph with regard to the recognition and quantification of pleural effusions. The findings of supine chest radiographs were compared to those of chest sonography in a total of 320 pleural cavities. The correct identification and quantification of a pleural effusion was possible by supine chest radiograph alone in only 55% of cases (176/320). In 20% (64/320) supine chest x-ray was falsely negative and in 15% (48/320) falsely positive. In 10% an existing effusion was in fact recognised on supine chest x-ray; however the amount of effusion was wrongly estimated. PMID- 1932729 TI - [Biliary obstruction: MR-cholangiography with a rapid gradient-echo sequence (2D CE-Fast)]. AB - Magnetic resonance (MR) was used to delineate the biliary tree in patients with obstructive jaundice originating from various types of malignant or benign processes at different locations. With the aid of a rapid sequential gradient echo acquisition (CE-Fast) and 3D post-processing, heavily T2-weighted images could be obtained to identify the site of obstruction in ten out of eleven patients. Slices were acquired during breath-holding periods of about 12 sec with a total examination time of 10-15 min. The three-dimensional display reliably demonstrated the dilated bile ducts in pre-stenotic areas whereas in the majority of cases post-stenotic ductal segments could not be visualised. PMID- 1932730 TI - [Conventional and cine-MRT in patients with aneurysms of the abdominal aorta]. AB - We studied 40 patients with aneurysms of the abdominal aorta by MRI. These results were compared with those obtained by real-time sonography (n = 40), angiography (n = 32) and CT (n = 16). In 30 patients the imaging results were compared--as far as possible--with the operative findings. MRI proved more reliable, especially if compared with sonography, in evaluating renal or iliac artery involvement. Mural thrombi were detected more often (93%) by MRI than by CT (85%) or sonography (83%). Cine-MRI showed strong turbulences in 33%. Turbulences did not correlate with the size of the aneurysm. PMID- 1932731 TI - [Age determination of venous thrombi by ultrasound]. AB - In addition to diagnosing deep-vein thrombosis of the lower limb and pelvis, determination of the age of the thrombus is of considerable importance in guiding treatment. The present study was done to find out whether thrombus age can be determined by ultrasound morphology. 138 examinations were carried out on 76 lower limbs with phlebographically demonstrated thrombosed veins. Diameter of the thrombosed vein, echogenicity of the thrombus and demarcation of the venous wall from its surroundings were determined by colour-coded duplex sonography. The results were compared with histological evidence or with the age of the thrombus as determined by history and clinical course. The diameter of the thrombosed vein in conjunction with the history and clinical data makes it possible to determine the age of a thrombus. Echogenicity of the thrombus and demarcation of the venous wall do not provide any reliable information on thrombus age. PMID- 1932732 TI - [Diagnosis of acute myositis. Magnetic resonance tomography with Gd-DTPA]. PMID- 1932733 TI - Thyroid-related papillary carcinoma presenting as a cystic lesion in the parapharyngeal space. PMID- 1932734 TI - [Interstitial pulmonary fibrosis in Recklinghausen's disease]. PMID- 1932735 TI - [Histiocytosis X of the lung. High-resolution CT and histology]. PMID- 1932736 TI - Program of the annual meeting of the American Society of Hematology. December 6 10, 1991, Denver, Colorado. Abstracts. PMID- 1932737 TI - Hemoglobin A2: origin, evolution, and aftermath. PMID- 1932738 TI - Absence of the human retinoblastoma gene product in the megakaryoblastic crisis of chronic myelogenous leukemia. AB - The human retinoblastoma gene (RB) product, which is involved in the control of cell cycle and tumor suppression, is constitutively expressed as a nuclear phosphoprotein in normal human cells. We examined leukemic cells from 22 patients with blast crisis of chronic myelogenous leukemia (CML) for alterations of the RB expression. Western blotting and flow cytometry with anti-RB-protein antibodies showed that all of five cases with megakaryoblastic crisis lacked the expression of the RB-encoded protein, whereas none of 17 cases with the other phenotypes such as myeloblastic or lymphoblastic crisis showed any abnormality. These findings suggest that megakaryoblastic transformation of CML might be lineage specifically associated with loss of the RB protein. PMID- 1932739 TI - High-dose recombinant interleukin-2 and acute myeloid leukemias in relapse. AB - Interleukin-2 (IL-2) is able to induce the regression of metastatic cancers when administered in vivo. IL-2-activated natural killer cells and lymphocytes show, in vitro, activities against leukemic cells. To assess if in vitro observations could have significant clinical relevance, we evaluated the in vivo activity of high-dose recombinant IL-2 (6 to 8 x 10(6) IU/m2/8H intravenous bolus for 5 days) in 10 patients with acute myeloid leukemias (AML) in relapse after chemotherapy (n = 7) or autologous bone marrow transplantation (n = 3). Two patients achieved a complete remission and one had a minimal improvement in his marrow blast cells. Response was observed after one cycle of IL-2 in the two patients achieving a complete remission. These two patients relapsed at 3 and 4 months. These results showing clinical activity of high-dose recombinant IL-2 in AML invite further evaluation of this new form of immunotherapy in other clinical situations, like an adjuvant setting for selected groups of high-risk patients. PMID- 1932740 TI - Minimal residual disease in patients with chronic myelogenous leukemia undergoing long-term treatment with recombinant interferon alpha-2b alone or in combination with interferon gamma. AB - Interferon (IFN) therapy has become widely used for the treatment of chronic myelogenous leukemia. Hematologic remissions can be induced in about 60% of patients. Moreover, in a small number of patients loss of the Philadelphia (Ph) chromosome and of the BCR-ABL rearrangement is observed. We have used genomic Southern blotting as well as a two-step polymerase chain reaction (PCR) method to score for BCR-ABL messenger RNA (mRNA) in patients with hematologic remission induced by treatment with IFN alpha-2b alone or in combination with IFN gamma. Concomitantly, cytogenetic analysis was performed. In 11 of 115 patients reported here, a complete loss of rearranged BCR fragments was observed in Southern blots of peripheral blood (PB) and/or bone marrow (BM) cell samples. Malignant marker bands disappeared first in the PB. In six patients, this genotype remained stable, whereas in five patients, low-intensity, rearranged bands reappeared despite continuation of treatment. The reappearance of the malignant marker was not accompanied by a clinical relapse. Ph-negative metaphases were observed in PB cells of four patients and in the PB and BM cells of two of these patients. In the samples of the other patients, residual Ph-positive cells were detected. By two-step PCR, residual BCR-ABL rearranged transcripts were found in samples of 10 patients. PMID- 1932741 TI - Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia. AB - In order to determine the efficacy and safety of ancrod, a rapid acting defibrinogenating drug, for patients with heparin-induced thrombocytopenia, 11 consecutive patients who required anticoagulant therapy because of venous thromboembolism and who developed acute heparin-induced thrombocytopenia or had a history of heparin-induced thrombocytopenia were treated with ancrod. Heparin therapy was discontinued (in patients receiving heparin) and ancrod started at a dose of 1 to 2 U/kg every 24 hours with subsequent daily doses adjusted to maintain fibrinogen levels between 0.5 and 1.0 g/L. Ancrod was continued until warfarin had become effective. The platelet count increased to more than 150 x 10(9)/L within 2 to 10 days in all thrombocytopenic patients. Two patients with a history of heparin-induced thrombocytopenia maintained normal platelet counts while receiving ancrod. Two patients had recurrent venous thrombosis while receiving warfarin, 10 days after ancrod was discontinued: one of these patients had metastatic pancreatic carcinoma and developed phlegmasia cerulea dolens and the other patient developed a venographically proven extension of her deep venous thrombosis. One patient suffered a bleeding episode into the thigh with a 16-g/L decrease in her hemoglobin level while receiving ancrod therapy. No other side effects were noted. Our experience indicates that ancrod therapy is a reasonable approach for patients with heparin-induced thrombocytopenia who require anticoagulant therapy. PMID- 1932742 TI - Identification of novel protein tyrosine phosphatases of hematopoietic cells by polymerase chain reaction amplification. AB - Polymerase chain reaction (PCR) conditions were used to amplify cDNAs that encode putative protein tyrosine phosphatases (PTPs) from a murine interleukin-3 dependent myeloid cell line. Primers for the reactions were based on conserved sequences of the catalytic domain that are shared among all known PTPs. Sequencing of 100 PCR-amplified cDNA clones identified seven different cDNA sequences. Two of these sequences were identical to the murine PTP genes Ly5/CD45/LCA and LRP/R-PTP-alpha. Two of the cDNA sequences were 95% identical to human PTP epsilon (HPTP epsilon) and rat brain PTP (PTP1B), respectively, and are likely to represent their murine homologs. Three of the cDNA sequences encoded novel potential PTPs. One of the putative PTPs was ubiquitously expressed while a second was predominantly expressed in brain, kidney, and liver and at much lower levels in a variety of other cell tkpes and tissues. The third novel putative phosphatase was expressed primarily in hematopoietic cells and tissues in a pattern that was comparable with Ly5/CD45/LCA. Further characterization of these novel PTPs will provide insights into the growth regulation of hematopoietic cells. PMID- 1932743 TI - An autocrine role for erythropoietin in mouse hematopoietic cell differentiation. AB - Erythropoietin (epo) is the primary regulator of the rate of red blood cell formation in mammals. Because it is formed in the kidney and acts on the bone marrow, its action is classically endocrine. We have shown by PCR that marrow cells contain epo mRNA and that antisense oligodeoxynucleotides, to both epo and its receptor, act on multipotent hematopoietic cells to cause a decrease in mixed erythroid:nonerythroid colonies. The antisense oligonucleotides also cause an increase in mixed nonerythroid colonies with no effect on erythroid burst formation. Sense oligonucleotides have no effect. The antisense suppression is not due to adherent cells, cycling late differentiated cells or lymphocytes, and not reversed by exogenous epo. We conclude that normal erythroid differentiation may have an early phase that is dependent on an internal autocrine mechanism involving epo and its receptor. PMID- 1932744 TI - Prenatal diagnosis of neonatal alloimmune thrombocytopenia using allele-specific oligonucleotide probes. AB - The prediction of neonatal alloimmune thrombocytopenia (NATP) in affected families has, in the past, been based on information about gene frequencies of the antigen systems involved, parental phenotyping, and fetal platelet counts. We explored the feasibility of allele-specific oligonucleotide probe typing for PIA antigens to determine the risk of second or subsequent fetuses in families where one infant had a diagnosis of anti-PIA1-mediated NATP. A total of eight families at risk for delivering an affected fetus were studied with both serologic and oligonucleotide typing. The correlation between serologic and oligonucleotide PIA types was 100%. Similarly, in an additional eight families not at risk for PIA1 mediated NATP, serologic and oligonucleotide typing maintained a perfect correlation. DNA isolated from fetal leukocytes as well as fetal amniocytes was successfully typed using this technology. Oligonucleotide-based typing of fetuses at risk for NATP whose fathers are heterozygous for the PIA antigens allows early recognition of affected fetuses so that prenatal therapy of mothers can be instituted if necessary. When fetuses are found to be unaffected, invasive, and/or expensive, prenatal interventions can be avoided. PMID- 1932745 TI - Isolation from commercial aurintricarboxylic acid of the most effective polymeric inhibitors of von Willebrand factor interaction with platelet glycoprotein Ib. Comparison with other polyanionic and polyaromatic polymers. AB - Solutions of commercial aurintricarboxylic acid (ATA) inhibit ristocetin- or shear stress-induced, von Willebrand factor (vWF)-mediated platelet aggregation by interacting with vWF and blocking its attachment to platelet membrane glycoprotein Ib. ATA has also been shown to prevent cyclic platelet clumping in a dog model of coronary artery thrombosis. Because these ATA solutions are actually a heterogeneous mixture of polyanionic, polycarboxylic polyaromatic polymers of molecular weight (Mr) 200 to greater than 6,000, we separated the most effective inhibitory components of commercial ATA using exclusion chromatography. ATA polymers larger than Mr 700 inhibited ristocetin-induced, vWF-mediated platelet aggregation more effectively than smaller ATA polymers, whereas shear-induced, vWF-mediated platelet aggregation was optimally inhibited by ATA polymers of Mr greater than or equal to 2,500. Platelet aggregation mediated by vWF was not inhibited by a nonphenolic, polyanionic polymer (polyglutamic acid) or by a polyphenolic ATA-like polymer (aurin) devoid of carboxyl groups. Polyanionic, polysulfonated aromatic polymers (polystyrene sulfonate) of Mr 35, 17.4, 8, and 4.6 x 10(3) inhibited ristocetin- and shear-induced, vWF-mediated aggregation with less potency on a mass/volume basis than large polymers of ATA. We conclude that a polyanionic, polycarboxylated, polyphenolic ATA polymer of Mr 2,500 is optimally potent as an inhibitor of shear- and ristocetin-induced, vWF-mediated platelet aggregation and is likely to be more effective than solutions of commercial ATA as an anti-arterial thrombotic agent. PMID- 1932746 TI - Molecular basis for antithrombin III type I deficiency: three novel mutations located in exon IV. AB - Antithrombin III (AT III) type I deficiencies are characterized by a 50% decrease of both immunoreactive and functional protein and carry a high risk of thrombotic complication. We have studied the molecular basis for such deficiencies by asymmetric polymerase chain reaction amplification and direct sequencing of the seven exons and of the intron-exon junction of the AT III gene. Three different mutations were observed in the exon IV: a 4-bp deletion, a 2-bp deletion, and a nucleotide insertion. Each of these mutations results in a frameshift introducing premature stop codons at positions 313, 309, and 232, respectively. These results were confirmed by dot-blot analysis with allele-specific oligonucleotide probes. Furthermore, no mutation was observed in the other six exons. The comparison of the type of mutations observed by our group in six cases of type I deficiencies and in 16 cases of type II heparin binding site variants deficiencies suggests that the former are caused by heterogeneous molecular abnormalities while the latter are caused by recurrent missense mutations. PMID- 1932747 TI - Binding of tissue plasminogen activator to human monocytes and monocytoid cells. AB - Monocytes and monocytoid cell lines previously have been shown to express receptors for plasminogen and urokinase (u-PA). In the present study, the monocytoid cell lines, U937 and THP-1, are shown to bind tissue plasminogen activator (t-PA) in a specific, saturable, and reversible manner. These cells bound t-PA with low affinity (kd = 0.67 to 0.97 mumol/L) and high capacity (0.71 to 3.3 x 10(6) receptors/cell). Human peripheral blood monocytes bound t-PA with a kd (0.9 mumol/L) similar to that of the monocytoid cells but with a lower capacity (0.17 x 10(6) sites/cell). These binding parameters also were similar to the low-affinity interaction of t-PA with endothelial cells as measured with the cells in suspension (kd = 0.73 mumol/L and 1.1 x 10(6) sites/cell). Lysine analogues and active or diisopropylfluorophosphate-inactivated u-PA inhibited t PA binding to monocytes, monocytoid cells, and endothelial cells with similar IC50 (concentration producing 50% inhibition) values, suggesting that the same recognition specificity mediates t-PA binding to all of these cell types. The existence of a high-affinity binding site for t-PA on monocytoid cells was also explored in detail. Unlike endothelial cells where plasminogen activator inhibitor-1 has been implicated in mediating a high-affinity interaction of t-PA with the cells, no evidence for a role of this inhibitor in ligand binding to the monocytoid cells was found. Furthermore, using both high and low 125I-t-PA concentrations, competition analyses with lysine analogues or u-PA, or treatment of the cells with carboxypeptidase B, failed to indicate the presence of distinguishable classes of t-PA binding sites. In sum, low-affinity receptors for t-PA are expressed at high density on monocytes and monocytoid cells, identifying a new element in the fibrinolytic arsenal of these cells. PMID- 1932748 TI - Effect of deletion of glycoprotein IIb exon 28 on the expression of the platelet glycoprotein IIb/IIIa complex. AB - We have isolated from an HEL cell cDNA library an alternatively spliced transcript for the platelet membrane glycoprotein IIb (GPIIb) that resulted from the deletion of the 34 amino acids of exon 28 of the GPIIb gene. Confirming an earlier report, we also detected this transcript in platelet mRNA. To determine the consequences of exon 28 deletion on the expression of the GPIIb/IIIa heterodimer, we expressed cDNA for GPIIb-28 in COS-1 cells, either individually or simultaneously with a cDNA for GPIIIa. When recombinant GPIIb-28 was expressed alone, it did not acquire resistance to the enzyme endo-beta-N acetylglucosaminidase H, was not cleaved into heavy and light chains, and was not transported to the cell surface. However, when recombinant GPIIb-28 was coexpressed with recombinant GPIIIa, GPIIb/IIIa heterodimers were assembled. Nevertheless, these heterodimers failed to complete posttranslational processing and were degraded intracellularly. Exon 28 contains one site for Asn-linked glycosylation. To determine if loss of this glycosylation site was responsible for the effects of exon 28 deletion, we removed the site from the exon 28 of intact GPIIb by oligonucleotide-mediated mutagenesis. However, absence of the carbohydrate appended to exon 28 did not prevent normal GPIIb/IIIa heterodimer expression. Our studies indicate that absence of the amino acids encoded by GPIIb exon 28 sufficiently perturbs the quaternary configuration of the GPIIb/IIIa heterodimer to impair its subsequent intracellular transport and processing. They also indicate that this alternatively spliced form of GPIIb mRNA, although present in megakaryocytes, is unlikely to make a significant contribution to the GPIIb/IIIa complexes expressed on platelets. PMID- 1932749 TI - Protein kinase C regulates proliferation of mast cells and the expression of the mRNAs of fos and jun proto-oncogenes during activation by IgE-Ag or calcium ionophore A23187. AB - Short-term stimulation (up to 16 hours) of interleukin-3 (IL-3)-dependent mouse bone marrow-derived mast cells, Abelson transformed mouse liver-derived mast cells, or rat basophilic leukemia cells by either IgE-Ag or calcium ionophore A23187 resulted in inhibition of their proliferation as measured by 3H-thymidine incorporation and MTT (tetrazolium) assays, and in accumulation of the mRNAs of c fos, c-jun, junB and slightly of junD proto-oncogenes. The involvement of protein kinase C (PKC) in these responses was investigated by using several approaches of enzyme activity regulation. Direct activation of the PKC was achieved by short term exposure of the cells to the PKC-specific activator phorbol 12-myristate-13 acetate (PMA). Inhibition of PKC activity was obtained by either prolonged treatment of the cells with PMA or by exposure of the cells to the PKC inhibitors H-7 and staurosporine. The results showed the following: (1) Short-term exposure of mast cells to PMA was sufficient to induce inhibition of proliferation. (2) An increase in PKC activity was associated with a decrease in the proliferation of IgE-dinitrophenol (DNP) or calcium ionophore A23187-stimulated cells. (3) A direct correlation was found between the increase in PKC activity and the increase in the level of the mRNAs of the jun proto-oncogenes in cells activated by both stimuli mentioned. (4) While an increase in PKC activity was associated with the upregulation of the level of c-fos mRNA during calcium ionophore A23187 stimulation, it showed the opposite effect on the expression of the mRNA of this proto-oncogene when the cells were triggered by IgE-DNP. Therefore, we concluded that PKC plays various roles in the expression of the mRNA of c-fos in activated mast cells depending on the stimulus involved. In addition, the expression of the mRNA of c-jun and junB proto-onogenes is not coordinately regulated with that of c-fos during immunologic stimulation. This discordancy, which is associated with the increase in PKC activity in mast cells, may play a role in the regulation of the transcription of AP-1-responsive genes, and therefore could be associated with the regulation of proliferation of these cells. PMID- 1932750 TI - The gene for the alpha 4 subunit of the VLA-4 integrin maps to chromosome 2Q31 32. AB - The VLA-4 integrin (CD49d/CD29), initially discovered on lymphoid cells, is actually known to be highly expressed on T cells, B cells, monocytes, and derived cell lines. Unlike other VLA integrins, mainly involved in cell-matrix adhesive interactions, VLA-4 has also been implicated in several cellular interactions. Based on the published alpha 4 cDNA sequence, a 1,142-bp alpha 4 cDNA fragment was amplified using the polymerase chain reaction. This fragment was used to isolate three overlapping genomic clones from a phage library. By Southern analysis with the cDNA probe, and using the polymerase chain reaction on DNA isolated from a panel of human/mouse somatic cell hybrids, the alpha 4 gene was mapped to chromosome 2. Fluorescence in situ hybridization confirmed this assignment and allowed a more precise mapping to chromosome 2q31-32. PMID- 1932751 TI - Alteration in bone marrow adherent layer growth factor expression: a novel mechanism of chronic myelogenous leukemia progression. AB - Philadelphia chromosome1 positive (Ph1) chronic myelogenous leukemia (CML) is characterized by metamorphosis of the chronic phase to blastic crisis. However, cellular events associated with this transition are poorly understood. To examine the possible participation of hematopoietic growth factors in this process, we studied growth factor expression in adherent layers of bone marrows derived from CML Ph1 patients in various stages of the disease. Interleukin-1 beta (IL-1 beta) and IL-6 mRNA were expressed in five of six patients, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in one of six patients with myeloid/undifferentiated blast crisis. In addition, leukemia inhibitory factor (LIF) expression was increased in four of six patients with myeloid/undifferentiated blast crisis phase of the disease. IL-1 beta was also detected in bone marrow adherent layer conditioned medium from two of these patients. These results were in sharp contrast to the lack of detectable levels of uninduced IL-1 beta, IL-6, and GM-CSF mRNA, in samples derived from 4 patients in lymphoid blastic crisis, 3 in accelerated, and 11 in chronic phases of the disease, or from normal controls. The possibility of a paracrine loop formation, whereby the adherent layers representing the bone marrow stroma are induced to express hematopoietic growth factors, was supported by our finding IL-1 beta mRNA expression in the leukemic blast cells in three of four studied patients in blast crisis and IL-1 beta protein production in seven of eight patients studied. Finally, coculturing CML blast crisis cells onto pre-established adherent layers induced the expression of both IL-1 beta and IL-6 genes. From this preliminary study, it appears that abnormal expression of growth factors is a common event with CML Ph1 progression. We hypothesize that IL-1 beta generated by the transformed malignant clone stimulates the marrow stroma to produce various growth factors, and that this process may play a role in disease progression. PMID- 1932752 TI - BCR-ABL rearrangements in children with Philadelphia chromosome-positive chronic myelogenous leukemia. AB - Leukemia cells from adults with Philadelphia (Ph1)-chromosome positive chronic myelogenous leukemia (CML) have a characteristic molecular rearrangement between the BCR and ABL genes whereby major breakpoint cluster region (Mbcr) exons 2 or 3 are joined to ABL exon II. Ph1-chromosome positive CML is uncommon in children and it is unknown whether these children have similar rearrangements. We studied 17 children with Ph1-chromosome positive CML. Five were studied for Mbcr rearrangement using Southern blotting, nine for the presence of chimeric BCR-ABL mRNA using reverse transcription and polymerase chain reaction, and three for both. All eight children studied by Southern blotting had BCR rearrangement. Of 12 children in whom BCR-ABL mRNA was studied, 10 had Mbcr exon 2 joined to ABL exon II, one had Mbcr exon 3 joined to ABL II, and one had both Mbcr-ABL junctions. These data indicate a similarity to adult CML. However, mRNA processing in children may preferentially splice Mbcr exon 2 to ABL exon II. No child had BCR exon 1 joined to ABL exon II, the rearrangement typical of childhood Ph1-chromosome positive acute lymphoblastic leukemia. PMID- 1932753 TI - Significance of the P210 versus P190 molecular abnormalities in adults with Philadelphia chromosome-positive acute leukemia. AB - We investigated the significance of p210 and p190 molecular abnormalities in 32 adults with Philadelphia chromosome (Ph)-positive acute leukemia. p210 was detected in 15 patients (47%), p190 in 16 (50%), and both in one (3%). p210 was noted in 11 of 24 patients (46%) with acute lymphocytic leukemia, and in four of eight patients (50%) with acute myelogenous or undifferentiated leukemia. Among 29 patients with untreated disease (p210, 14 patients; p190, 15 patients), no significant differences in the two molecularly distinct groups were observed by pretreatment characteristics including age, degree of organomegaly, anemia, leukocytosis, thrombocytopenia, occurrence of karyotypic abnormalities in addition to Ph, or residual diploid metaphases. Complete response (CR) rates were also similar. Although the remission duration tended to be longer with p190 (P = .08), the differences were minor (median duration 29 v 20 weeks) and not paralleled by differences in survival rate. In 10 patients studied by karyotypic analysis in remission, two of four patients with p190 and two of six patients with p210 showed 100% normal metaphases. One of the seven patients (14%) with p210 who achieved CR manifested a morphologic picture of second chronic-phase chronic myelogenous leukemia lasting for 1 month. We conclude that the molecular studies in Ph-positive acute leukemia are not associated with significantly different clinico-laboratory, karyotypic, or prognostic implications. PMID- 1932754 TI - c-myc hypermutation is ongoing in endemic, but not all Burkitt's lymphoma. AB - Deregulation of c-myc oncogene secondary to chromosomal translocation appears to play an essential role in the genesis of both endemic (African) Burkitt's lymphoma (eBL) and sporadic Burkitt's lymphoma (sBL). In most eBL, mutations in or near exon 1 disrupt normal c-myc regulatory sites. We examined c-myc sequences from a patient with sBL and two patients with eBL to determine (1) whether mutation is ongoing as the tumor clone expands, (2) the nature of mutations in the protein-coding exons 2 and 3, and (3) the extent of c-myc hypermutation in the two clinical forms of BL. Using the polymerase chain reaction (PCR), we amplified segments of c-myc from bulk tumor samples, cloned the products into plasmid vectors, and sequenced multiple subclones of each segment. The mutation frequencies in the control (remission bone marrow) and sBL tumor subclones were 0.65 x 10(-4) and 3.0 x 10(-4) (mutations/base), respectively (P greater than .25). Subclones from the two eBLs exhibited mutation frequencies of 20 x 10(-4) and 16 x 10(-4), respectively (P less than .001 v control). In addition to the consensus mutations seen in one eBL, a random pattern of unshared mutations was observed throughout c-myc in both samples, demonstrating that mutations may be introduced in a stepwise fashion. We noted a clear excess of transitions over transversions (30:9), which is qualitatively similar to the pattern observed in diverse examples of eukaryotic gene mutation. These data demonstrate that c-myc hypermutation is an ongoing process as the eBL tumor clone expands, is qualitatively different from immunoglobulin gene hypermutation, and is not a universal feature of BL, perhaps reflecting the nature of the translocation or the stage of tumor cell maturation. PMID- 1932755 TI - Diagnosis of thalassemia using cDNA amplification of circulating erythroid cell mRNA with the polymerase chain reaction. AB - We have developed a technique to diagnose the alpha- and beta-thalassemia (thal) syndromes using the polymerase chain reaction to amplify cDNA copies of circulating erythroid cell messenger RNA (mRNA) so as to quantitate the relative amounts of alpha-, beta-, and gamma-globin mRNA contained therein. Quantitation, performed by scintillation counting of 32P-dCTP incorporated into specific globin cDNA bands, showed ratios of alpha/beta-globin mRNA greater than 10-fold and greater than fivefold increased in patients with beta 0- and beta (+)-thal, respectively, as well as a relative increase in gamma-globin mRNA levels. Conversely, patients with alpha-thalassemia showed a decreased ratio of alpha/beta-globin mRNA proportional to the number of alpha-globin genes deleted. This methodology of ascertaining ratios of globin mRNA species provides a new, simplified approach toward the diagnosis of thalassemia syndromes, and may be of value in other studies of globin gene expression at the transcription level. PMID- 1932756 TI - Hereditary elliptocytosis due to both qualitative and quantitative defects in membrane skeletal protein 4.1. AB - Protein 4.1 is an important structural component of the membrane skeleton that helps determine erythrocyte morphology and membrane mechanical properties. In a previous study we identified a case of human hereditary elliptocytosis (HE) in which decreased membrane mechanical stability was due to deletion of 80 amino acids encompassing the entire 10-Kd spectrin-actin binding domain. A portion of this domain (21 amino acids) is encoded by an alternatively spliced exon that is expressed in late but not early erythroid cells. We now report a case of canine HE in which the abnormal phenotype is caused by failure to express this alternative peptide in the mature red blood cell (RBC) membrane skeleton, in conjunction with quantitative deficiency of protein 4.1. Western blotting of RBC membranes from a dog with HE showed a truncated protein 4.1 that did not react with antibodies directed against the alternative peptide. In addition, sequencing of cloned reticulocyte protein 4.1 cDNA showed a precise deletion of 63 nucleotides comprising this exon. Normal dog reticulocytes did express this exon. Expression of this 21 amino acid peptide during erythroid maturation is therefore essential for proper assembly of a mechanically competent membrane skeleton, because RBCs lacking this peptide have unstable membranes. PMID- 1932757 TI - Shedding of transferrin receptor from rat reticulocytes during maturation in vitro: soluble transferrin receptor is derived from receptor shed in vesicles. AB - Measurements of circulating transferrin (Tf) receptor are useful in assessing erythropoiesis; however, steps involved in the generation of soluble Tf receptor from cellular receptor are incompletely understood. To obtain a better understanding of this process, we investigated the loss of Tf receptor during terminal maturation of rat reticulocytes in vitro. Previous studies have identified Tf receptor-containing vesicles in the culture medium of maturing reticulocytes. In the present study, vesicle-free reticulocyte culture medium was found to contain functional and immunoreactive soluble Tf receptor, which increased over time. During a 44-hour incubation, Tf receptor on reticulocytes decreased by approximately 69%, while, of the Tf receptor shed to the medium, 65% was present in vesicles and 35% was in a soluble form. Isolated vesicles reincubated in fresh medium released soluble Tf receptor to the medium. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the isolated soluble receptor protein was mainly 190 Kd and 95 Kd under nonreducing and reducing conditions, respectively, similar in size to the vesicular and cellular receptor. Our studies show that loss of Tf receptor from rat reticulocytes during maturation in vitro involves shedding of cellular Tf receptor in vesicles and release of soluble receptor from these vesicles. PMID- 1932758 TI - Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up. AB - Since 1980, 107 consecutive patients (pts) underwent bone marrow transplantation (BMT) for nonconstitutional severe aplastic anemia (SAA) at our institution. All received conditioning with Cytoxan (150 mg/kg) and thoraco-abdominal irradiation (6 Gy) from an HLA-identical sibling donor. Mean age was 19 years (5 to 46 years). Forty-nine pts had less than 0.2 x 10(9)/L PMN and 53 failed to respond to previous immunosuppressive therapy before BMT. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (22 pts), cyclosporine (52 pts), or both (33 pts). With a median follow-up of 45 months (12 to 120 months), overall actuarial survival was 68% (confidence interval 95%:9.7). Of 16 factors tested, five were shown to adversely influence survival by multivariate analysis: grade greater than or equal to 2 acute GVHD (relative risk [RR]: 5.5), prior immunosuppressive therapy (RR: 3.5), female as donor (RR: 2.4), nonidiopathic SAA (RR: 2), and more than 0.2 x 10(9)/L PMN AA (RR: 2). Because acute GVHD was the most potent factor for survival, we analysed risk factors for acute GVHD. By multivariate analysis, 2 of 14 factors tested were independent: male as recipient (RR: 3) and previous alloimmunization of the donor (RR: 4.3). On long-term follow up, chronic GVHD was observed in 49 pts of 89 surviving more than 100 days (55%). Multivariate analysis showed that infection before transplant (RR: 1.3) and previous history of acute GVHD (RR: 1.8) were associated with an increased risk of chronic GVHD. PMID- 1932759 TI - The site of erythropoietin production: localization of erythropoietin mRNA by radioactive in situ hybridization. PMID- 1932760 TI - Prognosis in children with the t(4;11)(q21;q23) acute leukemia. PMID- 1932761 TI - Effect of granulocyte-macrophage colony-stimulating factor on endothelial cells. PMID- 1932762 TI - Microvascular motricity and haemorheology effects of buflomedil. Symposium held during the International Congress on Angiology. Rome, September 21, 1989. Proceedings. PMID- 1932763 TI - Arteriolar vasomotion: implications for tissue ischemia. AB - Vasomotion, the rhythmical contraction and relaxation of the arterioles, is a natural property of the arteriolar microcirculation. It is observed clinically through related flow variations (flux motion) which are detected by laser Doppler flowmetry. It presents two distinct regimens: slow and fast waves, with frequencies of 1-2 and 10-20 cpm, respectively. Both activities are found in normal tissues, and their rate of incidence as well as their magnitude become significantly enhanced during abnormal conditions associated with low blood pressure and hypoperfusion. The institution of this activity by abnormal tissue conditions suggests that vasomotion is a reaction of the microcirculation aimed at improving microvascular function. PMID- 1932764 TI - Exercise-induced variations in muscle tissue oxygen pressure in claudicants: effects of buflomedil. AB - The amount of oxygen actually supplied to the ischemic muscle tissue of patients with intermittent claudication was quantified before and after a standardized pedal ergometric test. Muscle tissue pO2 was measured with micro-platin needle electrodes directly in the lower limb muscles at rest and 3, 10, 20 and 60 min after a 4-min work load. Time-dependent variations in the behavior of pO2 values as well as changes in the shapes of pooled pO2 histograms make it possible to monitor the effect of therapeutic measures. In claudicants (stage IIb) with ascertained occlusions or stenosis of the femoral artery or the pelvis region, it was demonstrated that the delayed increase in tissue pO2 after exercise could be improved by the infusion of 400 mg buflomedil. Comparison between the time related pooled histograms confirmed improvement of oxygen supply under the influence of this drug. PMID- 1932765 TI - Effects of buflomedil on microvascular disorders in diabetic patients. AB - The aim of this work was to evaluate the effect of buflomedil on hemorheologic, hemodynamic and microcirculatory properties in diabetic patients. Patients were 20 noninsulin-dependent diabetics with distal arteriopathy characterized by chronic hypoxia (transcutaneous oxygen pressure = 25.2 +/- 4.8 mm Hg). They were randomly assigned to two groups for a double-blind study versus placebo. The treatment consisted of a 4-hour intravenous perfusion of 400 mg of buflomedil or placebo as a daily dose during 7 days. Results showed significant improvements in hemodynamic parameters such as post-occlusive peak flow and time to peak flow at the end of buflomedil treatment. In the same manner, the transcutaneous oxygen pressure was found to be significantly increased after buflomedil treatment, whereas there was no modification by placebo. Indeed, red cell aggregation was significantly less important as a result of buflomedil treatment whilst red cell deformability was found to be significantly increased. These hemorheological improvements make the blood flow redistribution through the microcirculatory network easier and lead ultimately to better tissue oxygenation. PMID- 1932766 TI - [Alloplastic implants (HA) for edentulous ridge augmentation before fixed dentures. Longitudinal reevaluation and histology]. PMID- 1932767 TI - [The development of osseointegrated implants]. PMID- 1932768 TI - [Bacterial plaque and tartar]. PMID- 1932769 TI - Two years after. AB - EDS was founded in Paris two years ago. In this article the achievements are summarized. A great amount of the dreams of the committee have come true. All countries in the E.C. are represented by delegates. PMID- 1932770 TI - Oral problems related to the HIV infection: the role of the E.C. PMID- 1932771 TI - Perpetuation of misinterpretations due to lack of methodical insight. A critical re-evaluation of the determination of 45Ca release from intact guinea-pig atria. AB - 1. The evaluation of still more pretentious and complicated methods is accompanied by a decline of methodical knowledge outside of the own technical field. Interpretations or extrapolations are taken as granted without critical examination of the methodical steps applied. An example is given by re-evaluating the 45Ca release from isolated cardiac tissue and the possible interpretations. 2. 45Ca release and tissue Ca content were measured in isolated guinea-pig left atria during Ca equilibrium and under conditions known to induce net Ca movements. 3. At equilibrium condition (1.8 mM Na2+0) 3 exponential phase of 45Ca release from the atria were observed. The compartments contained 61%, 29% and 10% of total 45Ca; the t1/2 were 2, 12 and 90 min, respectively. 4. The release of 45Ca from the slowly exchanging compartment (t1/2 90 min) decreased during incubation in nominal Ca-free solution, although a net loss of tissue Ca occurred. Addition of EGTA (5 x 10(-5) M) to the washout medium abolished this retardation of 45Ca release. 5. At external Na+ concentrations below 40 mM (substituted by sucrose), the 45Ca release from the slowly exchanging compartment decreased. Simultaneously, the tissue Ca content increased massively. The 45Ca release was further reduced in Na-poor, nominal Ca-free solution. Under both conditions, the presence of EGTA in the washout medium normalized the rate of 45Ca release. 6. The results suggest that the apparent decline of 45Ca release from intact atria upon reduction of the external Ca and Na concentration does not reflect a decrease of the cellular efflux rate, but is the consequence of an enhanced re-uptake of 45Ca from the extracellular space into the myocardial cells. The probability for the released 45Ca either to escape into the organ bath or to become reabsorbed depends on the specific radioactivity of 45Ca in the extracellular space during the washout phase. Thus, this experimental procedure is not suited to demonstrate a Na-Ca exchange at the cardiac sarcolemma. PMID- 1932772 TI - Serotonin receptors and site-selective agents. AB - Few site-selective serotonergic agents are currently available; in fact, most of these agents might more appropriately be termed semi-selective in that they typically bind to at least two different populations of serotonin receptors. We describe the application of structure-affinity relationship (SAFIR) studies to the development of high-affinity and/or site-selective serotonergic agents; examples are provided from work conducted in our laboratories. Also discussed is the concept of selectively non-selective agents and their potential preclinical and clinical utility. A case is made for development of selective and nonselective serotonergic agents. PMID- 1932773 TI - Reactive modifications of the autonomous time structure in the human organism. AB - The spectrum of biological rhythms exhibits characteristic principles of biological time structure which also rule the functional behaviour. With increasing period lengths the rhythms become increasingly complex. In the long wave section the rhythmic functions find their corresponding cycles in the environment, whereas the shorter waves represent only endogenous autonomous rhythms, which maintain an internal time order by means of frequency- and phase coordination. Under resting conditions and in a state of complete adaptation only a few spontaneous rhythms dominate in the spectrum. However, under loading conditions as well as in pathological situations further periodicities come up. The spectrum of rhythms can be divided into certain blocks, with the period lengths predominating in each of these whole number frequency ratios forming a harmonic system. Frequency- and phase coordination establish a system of co action which favours the functional economy of the organism. A tripartite organization of the autonomous rhythms involves different functional behaviours with regard to frequency, amplitude, and phase. Slower rhythms act upon the faster rhythms preferably by modulating their frequencies, while changes of the faster rhythms influence the slower ones by enhancing their amplitudes, multiplying their period lengths and shifting their phases. In principle the reactions of living systems are periodically structured. Reactive periodicity brings to appearance an endogenous time structure, which prefers whole number relationships with the spontaneous rhythms. The phase position of reactive periods depends on the stimulus. The amplitudes dampen down with increasing compensation. From the medical point of view so-called circaseptan (about 7 days) reactive periods are of predominant interest. This periodicity can be observed in numerous adaptive and compensating processes. It does not depend on the external week cycle and was already known to the antiquity. PMID- 1932774 TI - Factors influencing the restitution of the duodenal and colonic mucosa after damage. AB - Rapid epithelial restitution is an important protective mechanism which enables the gastrointestinal mucosa to reestablish epithelial integrity following superficial injury within hours. In this study we examined the influence of an acidic luminal pH, removal of the necrotic layer, nutrient bicarbonate, calcium and sodium desoxycholate (Na-DOC) on restitution in the rabbit duodenum in vitro and the role of Na-DOC and calcium for rapid restitution of the human colon in vitro. Transmucosal potential difference (PD), short-circuit current (lsc) were measured and resistance against passive ion flux (R) was calculated. Electrophysiological changes paralleled morphological injury but did not necessarily reflect restitution in all experiments. The extent of mucosal injury was assessed by computerized real-time morphometry. 5 hrs after luminal exposure to 10 mH HCl for 10 min residual damage (RD) was 14% in the duodenum. Luminal pH of 3.0 (RD of 30%), removal of necrotic layer at acidic luminal pH (RD of 66%), absence of bicarbonate from the serosal solution (RD of 35% at neutral luminal pH; RD of 96% at acidic luminal pH) and removal of calcium from the serosal solution (RD of 58%) impaired restitution in the duodenum. Continuous postinjury luminal Na-DOC exposure did not influence restitution in the duodenum (RD of 19%). 5 hrs after luminal exposure to 0.5 mM Na-DOC for 10 min RD was 26% in the human colon. Continuous postinjury luminal Na-DOC exposure (RD of 51%) and removal of calcium from the nutrient solution (RD of 65%) impaired restitution in the human colon. Thus we conclude that restitution of the rabbit duodenum in vitro requires a necrotic layer and bicarbonate flux to withstand acidic luminal pH, while restitution is not affected by Na-DOC. In the human colon Na-DOC inhibits restitution. Both the duodenum and colon require calcium for rapid restitution. PMID- 1932776 TI - Electrical activity of canine gallbladder. AB - Our aims were to describe the myoelectrical activity in the single very thin layer of muscle of the canine gallbladder. The study was performed on 22 freshly removed canine gallbladders. Electrical activity was studied by the single sucrose-gap method and contractility of the tissue was measured simultaneously using a force transducer. The strips (15 x 1 mm) from different regions of gallbladder (fundus, corpus, neck) were cut in longitudinal, circular and oblique axes. The sucrose-gap apparatus together with connecting tubes, solutions and electrodes were kept at 37 degrees C and the initial tension applied to the tissue was set to 1 g. In 82.7% of recordings, spontaneous myoelectrical activity consisted of regular rhythmic changes in membrane potential similar to slow waves recorded in intestinal tissue. The overall mean frequency was 11.4 +/- 5.2 (mean +/- SD) cycles per min: 11.1 +/- 4.4 cycles per min in fundus, 11.9 +/- 6.2 cycles per min in corpus and 10.8 +/- 3.8 cycles per min in the neck of the gallbladder. In 84.2% of cases electrical activity correlated with mechanical activity and preceded it. No significant differences were seen between the electrical patterns in strips with different orientations or from the different regions of the gallbladder. PMID- 1932775 TI - Solcoseryl in prevention of stress-induced gastric lesions and healing of chronic ulcers. AB - Solcoseryl, a deproteinized extract of calf blood, protects the gastric mucosa against various topical irritants and enhances the healing of chronic gastric ulcerations but the mechanisms of these effects have been little studied. This study was designed to elucidate the active principle in Solcoseryl and to determine the role of prostaglandins (PG) and polyamines in the antiulcer properties of this agent. Using both, the radioimmunoassay and radioreceptor assay, EGF-like material was detected in Solcoseryl preparation. Solcoseryl given s.c. prevented the formation of stress-induced gastric lesions and this was accompanied by an increase in the generation of PGE2 in the gastric mucosa. Similar effects were obtained with EGF. Pretreatment with indomethacin, to suppress mucosal generation of prostaglandins (PG), greatly augmented stress induced gastric ulcerations and antagonized the protection exerted by both Solcoseryl and EGF. Solcoseryl, like EGF, enhanced the healing of chronic gastro duodenal ulcerations. This effect was abolished by the pretreatment with difluoromethylornithine, an inhibitor of ornithine decarboxylase, the key enzyme in the biosynthesis of polyamines. The healing effects of Solcoseryl and EGF was also reduced by prednisolone which decreased the angiogenesis in the granulation tissue in the ulcer area. These results indicate that Solcoseryl 1. contains EGF like material, 2. displays the protective and ulcer healing effects similar to those of EGF and involving both PG and polyamines and 3. acts via similar mechanism as does EGF. PMID- 1932777 TI - Musca domestica larval lipoprotein. AB - A larval specific high-density lipoprotein (HDL) has been isolated from Musca domestica hemolymph by a combination of density gradient and glycerol gradient ultracentrifugations. The larval lipoprotein has a density of 1.134 g/ml and is formed by at least four apoproteins with molecular weights equal to 26,000, 23,000, 21,000, and 20,000. This lipoprotein contains large amounts of hydrocarbons and phospholipids and minor amounts of diacylglycerols and cholesterol. The larval lipoprotein is completely distinct from lipophorin in regard to apoprotein composition, lipid moiety, physiological pattern, and immunological reactions. Larval lipoprotein is accumulated until the end of the feeding period. During the pupal molt this protein is utilized and is no longer detected after 2 days of pupal stadium. The results obtained imply a possible role of this protein in the puparia and/or pupal cuticle formation. Judging from the properties shown, the Musca domestica larval lipoprotein is a completely new type of insect lipoprotein. PMID- 1932778 TI - Ecdysteroid synthesis and molting by the tobacco hornworm, Manduca sexta, in the absence of prothoracic glands. AB - When a pair of prothoracic glands (PGs) were removed from Manduca sexta pupae on the day of pupation, the hemolymph ecdysteroid titer remained at a low level. When a portion of the gland pair was extirpated from pupae after the critical period for prothoracicotropic hormone release, the maximum hemolymph ecdysteroid titer was reduced in proportion to the mass of the PGs removed. These findings clearly showed that the PGs in intact pupae are responsible for the elevated ecdysteroid titer required to elicit adult development on schedule. When brains were removed on the day of pupation, the initiation of adult development was delayed for weeks or months. In contrast, pupae whose PGs were removed on the day of pupation initiated development only 7 days late, indicating the existence of an additional source of pupal ecdysteroids. Further, abdomens of male M. sexta that were isolated on the day of pupation initiated adult development spontaneously within 70 days. The implantation of day 0 pupal brains into these isolated abdomens accelerated the initiation of adult development and elicited synchronous adult development. The hemolymph ecdysteroid titer of those isolated abdomens receiving implants of brains increased within 5 days and reached a maximum level of 1.5 micrograms/ml. The analysis of hemolymph ecdysteroids by reverse-phase HPLC revealed that ecdysone was the major moiety and that the ecdysteroid composition was similar to that of normal, intact pupae that had just initiated adult development. These results demonstrate that the PGs are not requisite for adult development. An increased hemolymph ecdysteroid titer was also observed in isolated abdomens from which the testes were removed and in abdomens devoid of their digestive tract. Indeed, in the latter case, the ecdysteroid titer attained much higher levels than those observed for abdomens with intact guts. Despite numerous attempts to identify the tissue(s) in the isolated abdomens responsible for the increase in ecdysteroid titer, its identity remains unknown. PMID- 1932779 TI - Binding of vitellogenin to membranes isolated from mosquito ovaries. AB - The presence of specific receptors for vitellogenin (Vg) in ovary membranes of the mosquito, Aedes aegypti, was demonstrated by an in vitro binding assay. The binding reaction, which is dependent on pH and Ca2+, uses 4 micrograms membrane protein, 35S-Vg labeled metabolically by fat body culture in vitro, and unlabeled vitellin (Vn) for competition. At pH 7.0 and in the presence of 5 mM Ca2+, the binding of Vg to its receptor reaches equilibrium within 60-90 min at both 4 and 25 degrees C. The binding is specific to membranes prepared only from ovaries. While mosquito Vg and Vn bind with equal affinity to Vg receptors on ovary membranes, neither locust Vg nor mouse IgG has any measurable affinity towards these sites. Nonlinear least square analysis of the saturation isotherms is consistent with the presence of a single class of Vg receptors on ovary membranes with a dissociation constant (Kd) of 0.18 microM. PMID- 1932781 TI - Parasite-induced enhancement of hemolymph tyrosinase activity in a selected immune reactive strain of Drosophila melanogaster. AB - Larval hemolymph tyrosinase activity in Drosophila melanogaster was detected with high performance liquid chromatography with electrochemical detection. The enzyme hydroxylated L-tyrosine, and oxidized the diphenol substrates L-dopa and dopamine. In larvae of a selected immune-reactive strain the rates of tyrosine hydroxylation, dopa oxidation, and dopamine oxidation were markedly increased during the early stages of melanotic encapsulation of the eggs of the parasitic wasp Leptopilina boulardi. Tyrosinase activity was not modified in parasitized larvae of a selected susceptible strain of D. melanogaster, in which hosts the parasitoids developed unmolested. During the same period of parasitization, the amount of free tyrosine in immune reactive larvae was approximately three times higher than in susceptible hosts. These data indicate that the tyrosinase system of the immune reactive strain is activated during parasitization, and this results in the synthesis of some precursors which ultimately produce a melanotic and sclerotic capsule around the eggs of the parasite. Based on known genetic information of the enzyme system in Drosophila, it appears that at least two genes may be involved in the activation process, one associated with the proenzyme for monophenol oxidase activity, and the second with the proenzyme for diphenol oxidase activity. PMID- 1932780 TI - Developmental disruption of Pseudoplusia includens and Heliothis virescens larvae by the calyx fluid and venom of Microplitis demolitor. AB - Calyx fluid and venom from the braconid parasitoid Microplitis demolitor differentially affected the development of Pseudoplusia includens and Heliothis virescens. P. includens exhibited delays in larval development, supernumerary instars, and formed larval-pupal intermediates when injected with 0.01-0.10 wasp equivalents of calyx fluid. In contrast, H. virescens was relatively unaffected by calyx fluid regardless of dose. Venom did not affect the development of either host species, but appeared to synergize the activity of calyx fluid. This was particularly evident in H. virescens, where injection of 0.10-0.20 wasp equivalents of calyx fluid and venom induced the formation of a large number of intermediates while the same amount of calyx fluid did not. The particulate portion of M. demolitor calyx fluid was the only component that caused developmental delays and the formation of intermediates in both host species. Purified virus caused developmental alterations in P. includens, while trioxsalen treated calyx fluid did not affect development of P. includens or H. virescens. These data suggest the requirement for venom in parasitism may differ between host species, and that dosage plays an important role in interpreting the interaction between calyx and venom components. PMID- 1932782 TI - Stimulation of embryonic development in Microplitis croceipes (Braconidae) in cell culture media preconditioned with a fat body cell line derived from a nonpermissive host, gypsy moth, Lymantria dispar. AB - A cell culture medium, IPL-52B, was preconditioned with host fat body and two insect cell lines to determine if they would support embryonic development of Microplitis croceipes in vitro. The medium was preconditioned with the cell line IPL-LdFB, derived from fat body of the gypsy moth, Lymantria dispar, cell line IAL-TND1, derived from imaginal discs of the cabbage looper, Trichoplusia ni, and whole fat body tissue from host Helicoverpa zea. A second cell culture medium, Excell 400, was preconditioned with only the cell line, IPL-LdFB. Pregerm band eggs were dissected from third instar host larvae and incubated in the conditioned medium for 20 h. Newly laid parasitoid eggs did not develop in unconditioned IPL-52B, but did develop to germ band stage in unconditioned Excell 400. The IPL-52B medium conditioned with both cell lines induced germ band formation, but only the L. dispar cell line (IPL-LdFB) promoted significant development to eclosion comparable to host far body tissue. Excell 400 medium preconditioned with the cell line, IPL-LdFB also supported development to eclosion. PMID- 1932783 TI - [Study of carrier rate and immunity to group B streptococcus (GBS) in unmarried women]. AB - In order to study the carrier rate and immunity to Group B streptococcus (GBS) of unmarried women, an urinary culture was taken and blood serum was assayed by ELISA for type-specific antibody in female students. Heretofore there have been very few reports about GBS in unmarried women in Japan. The validity of urinary culture as a substitute for vaginal culture was initially studied. The carriage of GBS was evaluated by vaginal, anal and urinary cultures in 90 pregnant women. Carrier detection were 18 carriers (20.0%) by vaginal culture, 22 carriers (24.4%) by anal culture and 18 carriers (20.0%) by urinary culture. Fifteen of the 18 subjects (83.3%) detected as carriers by vaginal culture carried the same strain of GBS in urine. Therefore, an urinary culture appears to perform as well as the vaginal culture as a convenient test for GBS. Nineteen (16.2%) of 117 unmarried women had positive urinary cultures for GBS. Among the 19 with positive cultures for GBS, 3 (15.8%) were type Ia, 3 (15.8%) were type Ib, 8 (42.0%) were type III and 5 (26.4%) were other types. Type II was not detected. From the type specific antibody assay, the histogram of ODI (optimal density index) frequency of types Ia, Ib and III showed a concentration in a relatively narrow range at low ODI, while that of type II was dispersed over a relatively wide range. PMID- 1932784 TI - [Factors related to serum lipid levels in women of middle and old age--a community study]. AB - Serum lipid levels of 168 women ranging in age from 30 to 69 were measured at a mass health screening in an urban community in Saitama prefecture. Degree of obesity, skinfold thickness and blood pressure were measured and the relation between these physical measurements to serum lipid levels was studied. The results are as follows: (1) Mean total cholesterol level, degree of obesity, systolic blood pressure and diastolic blood pressure increased linearly with advancing age. (2) Simple correlation analysis disclosed that the level of total cholesterol was positively correlated to age, degree of obesity, systolic blood pressure and triglyceride level. HDL-cholesterol level showed a significantly negative correlation to degree of obesity, skinfold thickness and triglyceride level. Degree of obesity was positively correlated to skinfold thickness, systolic blood pressure, diastolic blood pressure, total cholesterol and triglyceride level, but was negatively correlated to HDL-cholesterol. Systolic blood pressure had a positive correlation with age, degree of obesity, diastolic blood pressure, total cholesterol and triglyceride level. (3) Principal component analysis, when performed with the variables age, degree of obesity, skinfold thickness, systolic blood pressure, diastolic blood pressure, level of total cholesterol, triglyceride and HDL-cholesterol, showed that subjects could be divided into the group having obesity with low HDL-cholesterol (first principal component), the hypertensive group (second principal component), and the group having hyperlipidemia with advancing age (third principal component). (4) Multiple regression analysis was also carried out, taking HDL-cholesterol level as the dependent variable, and age, degree of obesity, systolic blood pressure, total cholesterol and triglyceride level as independent variables. Degree of obesity and triglyceride level were negatively related to HDL-cholesterol. PMID- 1932785 TI - [Relationship between referral and patient characteristics]. AB - In order to evaluate the relationship between referral and patient characteristics, 594 new patients utilizing Saga Medical School general clinic were studied using a questionnaire and chart review. Results obtained are as follows: 1) Fifty-eight patients (10%) came for follow-up of mass screening tests, 174 patients (29%) were self-referral, the remaining 362 patients (61%) were under previous care by other physicians. Only 64 patients (11%) had a referral letter. 2) Those patients who were not advised to visit our clinic by non-medical personnel, patients who were seriously ill, elderly patients, residents in distant area, and those with medical problems tended to have a referral letter. 3) Of the 64 patients having referral letters, 15 (23%) took the initiative in asking their previous doctor to write a referral letter. Patients who were highly educated had a greater tendency to request referral letters. 4) The reasons cited by the patients without a referral letter included "Did not think of the necessity" (22%), "Wanted to confirm diagnosis" (22%), "Did not want to make the doctor lose face" (16%), "No improvement in symptoms" (14%) These results indicate that education of patients and the general public, and establishing good physician-patient communication and trust are necessary for increasing the use of referral letter. PMID- 1932786 TI - [The smoking habits of pregnant women and their husbands, and the effect on their infants]. AB - A survey of the smoking habits of 3,025 couples, whose infants were receiving medical examinations, was conducted before and after pregnancy to determine the effect of smoking patterns of the parents on the newborn infant. Of the husbands 55.2% were smoking before pregnancy; 53.4% during pregnancy; and 51.8% after delivery. During pregnancy proportion of smokers decreased by only 1.8%. The percentages for wives, on the other hand, were 13.9%, 4.4%, and 5.3% respectively showing a reduction of 9.5% during pregnancy. Young couples, under 24 years of age, those with low educational backgrounds, and self-employed husbands showed the highest proportion of smokers. Examination of the relation between parents' smoking habits and their effect on the newborn infants, showed no difference in weeks of gestation nor in height. However, the infants of smoking parents were on the average 99.6 grams lighter at birth (p less than 0.02) and the rate of SFD was higher (p less than 0.05). The relative risk for SFD appearance was 1.21 with a smoking father, and 1.39 with both parents smoking. Husbands who decreased or stopped smoking during the pregnancy were largely in the 30 to 34 year old category, university graduates, and those whose wife was having their first baby. A remarkable decrease was observed in the average weight at birth of infants with a mother smoking 6 cigarettes a day or with father smoking 20 cigarettes a day compared to non-smoking parents, especially in the case of female infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932787 TI - [A study on the estimation of semi-health based on subjective symptoms]. PMID- 1932788 TI - [A study of health care, medical care and social welfare systems in the rural city of Koga based on a questionnaire survey]. PMID- 1932789 TI - [Epidemiological factors affecting place of terminal care and of death in the elderly]. AB - To clarify the factors associated with the location where terminal care and death occurs in the elderly, we conducted interviews of family members who had cared for elderly persons who died from cerebral infarction in Fukui City, Sabae City, and Oono City in 1985. Subjects selected had conscious levels that were clear or Level 1 on the Japan Coma Scale at the onset of disease and whose debilitation had exceeded six months. We evaluated the characteristics of three groups, Group 1 comprising 21 subjects who had died in a hospital after both institutional and home care, Group 2 being 30 people who had died at home after a similar course of treatment as Group 1, and Group 3 being 18 subjects who had died at home after non-institutional care. In Group 1, elderly spouses of the subjects performed a larger part of the care than in the other groups. Caregivers who were members of the same household as the subjects had higher rates of having jobs other than housekeeping and of receiving medical treatment for some disease in Group 1 than in the other groups. Subjects in Group 2 received relatively more care in their own households and obtained greater amount of medical service assistance. Subjects in Group 3 experienced the least amount of disturbance in daily living activities, the shortest period of debilitation, and had the most household members able to take care of them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932790 TI - [Secular trends in prevalence and incidence of atrial fibrillation and associated factors in a Japanese rural population]. AB - To investigate secular trends in prevalence and incidence of atrial fibrillation and associated factors, data from population studies of a northeast rural Japanese community, were explored. Cross-sectional studies for men and women aged 40-69 year were conducted in 1963-1966, 1972-1975 and 1984-1987. Age-adjusted prevalence rates of atrial fibrillation show no significant change in both men and women during these three periods. Over 80% of atrial fibrillation in each period showed no clinical evidence of rheumatic valvular disease, myocardial infarction, idiopathic cardiomyopathy, congenital heart disease and hyperthyroidism. Cohorts of men and women aged 40-69 year without atrial fibrillation at baseline were constructed in 1963-1966 (1,920 persons) and in 1972-1975 (2,325 persons) and followed until 1974 and 1987, respectively. In both cohorts, incidence of atrial fibrillation without these organic diseases was positively associated with hypertension related funduscopic abnormality and urine protein. Age-adjusted incidence rates of atrial fibrillation declined in both men and women between the two cohorts. This decline which was greater in hypertensives than in normotensives may in part reflect improvements in hypertension control in this community. PMID- 1932791 TI - Ethical counseling for house staff considering a strike. PMID- 1932792 TI - An analysis of the ACOG and AAP ethics statements on conflicts in maternal-fetal care. PMID- 1932793 TI - Confidentiality: a survey in a research hospital. AB - Despite the many justifications for protecting patient confidentiality, we recognize that confidentiality cannot be absolute. Our world of automated information and easy access and storage poses many threats to confidentiality. This paper has described a survey conducted at the NIH Clinical Center to assess the knowledge, attitudes, and behaviors of clinical physicians and nurses about confidentiality of patient information. The survey findings demonstrate the need for reminders and increased awareness about confidentiality in our setting. Most of the survey respondents had a good knowledge of what was expected of them, and they believed that confidentiality was important and maintaining it was their responsibility. Of interest was that in several simulated clinical situations, there was a discrepancy between what respondents indicated they should do and what they thought they would do. The biggest discrepancies appeared in situations that involved overhearing a patient conversation on the elevator, approaching an unfamiliar person who is reading a medical record in the nurses' station, and answering a patient's inquiry about the status of another patient. The findings support the speculation that this difference may be attributed to discomfort or decreased awareness, and not necessarily to lack of knowledge. Results indicate that policies and administrative expectations should be frequently communicated and enforced, and that educational programs that address issues of confidentiality should be provided. The results of this survey have been influential in guiding educational strategies and administrative activities at the clinical center. The clinical center initiated a confidentiality awareness campaign, displaying a new poster every three months in strategic locations and distributing other tangible reminders (such as pens, magnets, and buttons) containing the same confidentiality message.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1932794 TI - Patients as "subjects" or "objects" in residency education? PMID- 1932795 TI - In whose voice? Composing a lifesong collaboratively. PMID- 1932796 TI - Future directions in clinical ethics. PMID- 1932797 TI - Medical treatment after brain death: a case report and ethical analysis. PMID- 1932798 TI - Personal choices: communication between physicians and patients when confronting critical illness. PMID- 1932799 TI - Confidentiality in cases of rape: a concept reconsidered. PMID- 1932800 TI - A clarification. PMID- 1932801 TI - Patients: strangers or intimates? PMID- 1932802 TI - Should newborns receive analgesics for pain? PMID- 1932803 TI - Sedation before ventilator withdrawal. PMID- 1932804 TI - Is active killing of patients always wrong? PMID- 1932805 TI - Whisper down the lane: AIDS, privacy, and the hospital "grapevine". PMID- 1932806 TI - The importance of understanding suffering for clinical ethics. PMID- 1932807 TI - The role of suffering and community in clinical ethics. PMID- 1932809 TI - Viroids: from thermodynamics to cellular structure and function. PMID- 1932808 TI - The intriguing viroids and virusoids: what is their information content and how did they evolve? PMID- 1932810 TI - Cells expressing ENOD2 show differential spatial organization during the development of alfalfa root nodules. AB - We have used in situ hybridization to examine the spatial organization of cells expressing the early nodulin gene (ENOD2) during the development of alfalfa root nodules. ENOD2 gene expression was found in the nodule parenchyma, uninfected cells surrounding the symbiotic region of both effective and ineffective nodules. However, in empty nodules, ENOD2 gene expression was found in a mass of parenchyma cells at the base of the nodule. Similar results were also observed in 11-day-old nodules that contained infected cells but that had not yet begun to express leghemoglobin. Although early events of nodulation result in the induction of ENOD2 expression in cells at the nodule base, the pattern of cells expressing ENOD2 during nodule growth appears to be correlated with the development of other peripheral tissues. PMID- 1932811 TI - The TR-DNA region carrying the auxin synthesis genes of the Agrobacterium rhizogenes agropine-type plasmid pRiA4: nucleotide sequence analysis and introduction into tobacco plants. AB - We have determined the nucleotide sequence of a 6-kilobase fragment of the Agrobacterium rhizogenes plasmid pRiA4 TR-region that carries genes (aux1 and aux2) responsible for auxin biosynthesis in transformed plant cells. Sequence analysis revealed two open reading frames corresponding to proteins of 749 amino acids for the aux1 gene and 466 amino acids for the aux2 gene. We observed significant similarity between the amino acid sequences deduced from the pRiA4 aux genes and those of the auxin biosynthesis genes of A. tumefaciens octopine type Ti plasmids, the iaaM and iaaH genes of Pseudomonas savastanoi, and different genes of the pRiA4 TL-region; however, the 5'-flanking regions of the pRi and pTi auxin biosynthesis genes were found to be completely different. Transgenic tobacco plants containing this entire 6-kilobase fragment of the pRiA4 TR-region have been obtained. Regenerated plants are phenotypically normal. The aux1 gene is not or is very weakly expressed in these plants, but expression of the aux2 gene leads to a modified root phenotype when plants are grown on medium containing an auxin precursor (naphthalene acetamide). PMID- 1932812 TI - Role of T-region borders in Agrobacterium host range. AB - The limited host range AB3 strain of Agrobacterium tumefaciens induces tumors by transferring two T-regions, TA and TB. TA is a deleted version of the well-known biotype I octopine TL-region that lacks the iaa and ipt genes, but carries an intact oncogene, gene 6b, and typical left and right border sequences. TB carries two iaa genes that together code for the synthesis of indoleacetic acid. Gene 6b and the iaa gene act synergistically when transferred in a coinoculation experiment. The TA-region of the limited host range isolate Ag57 is related to the TA-region of AB3, but differs from it at several positions. The most significant difference is the absence of the right border region. In spite of this, Ag57 and the exconjugant strain C58C9(pTiAg57) induce normal tumors on Nicotiana rustica and Vitis vinifera. Various experiments indicate that gene 6b of the Ag57 TA-region is active and transferred in spite of the absence of the right border. On N. tabacum, C58C9(pTiAg57) is nononcogenic but becomes oncogenic when the pTiAg57 TA-region is restored by the right TA border sequence of pTiAB3. Thus, the right TA border sequence of the biotype III limited host range strains is required for tumor induction on some hosts, but not on others. PMID- 1932813 TI - Pathogenesis-related acidic beta-1,3-glucanase genes of tobacco are regulated by both stress and developmental signals. AB - Three pathogenesis-related (PR) proteins of tobacco are acidic isoforms of beta 1,3-glucanase (PR-2a, -2b, -2c). We have cloned and sequenced a partial cDNA clone (lambda FJ1) corresponding to one of the PR-2 beta-1,3-glucanases. A small gene family encodes the PR-2 proteins in tobacco, and similar genes are present in a number of plant species. We analyzed the stress and developmental regulation of the tobacco PR-2 beta-1,3-glucanases by using northern and western analyses and a new technique to assay enzymatic activity. Stress caused by both thiamine and tobacco mosaic virus (TMV) infection resulted in a dramatic increase in the levels of PR-2 mRNA, protein, and enzyme activities. The increased PR-2 gene expression in upper uninoculated leaves of plants infected with TMV also suggests a role in systemic acquired resistance. During floral development, a number of beta-1,3-glucanase activities were observed in all flower tissues. However, PR-2 polypeptides were observed only in sepal tissue. In contrast, an mRNA that hybridized to the PR-2 cDNA was present in stigma/style tissue and the sepals. Primer extension analysis confirmed the identity of the PR-2 mRNA in sepals, but indicated that the beta-1,3-glucanase gene expressed in the stigma/style of flowers was distinct from the PR-2 genes. The induction of PR-2 protein synthesis by both stress and developmental signals was accompanied by a corresponding increase in the steady-state levels of PR-2 mRNA, suggesting that PR-2 gene expression is regulated, in part, at the level of mRNA accumulation. PMID- 1932814 TI - Infectious and genetic manifestations of prion diseases. PMID- 1932815 TI - Differential expression of tomato proteinase inhibitor I and II genes during bacterial pathogen invasion and wounding. AB - Expression of proteinase inhibitor I and II genes was investigated during infection by Pseudomonas syringae pv. tomato, the causal agent of bacterial speck disease in tomato. Inoculation of leaves with P. s. pv. tomato of two inbred tomato lines that are resistant and susceptible to the pathogen resulted in the accumulation of proteinase inhibitor I and II mRNAs in this organ. Our data showed that in the lines used in this study, proteinase inhibitor II mRNAs accumulated in leaves to higher levels than proteinase inhibitor I mRNA in response to P. s. pv. tomato infection and wounding. Proteinase inhibitor II mRNAs accumulated more rapidly in disease-resistant than in disease-susceptible plants. Proteinase inhibitor I mRNAs were first detected in the disease susceptible line during infection and wounding. In contrast to wounding, the systemic induction of these genes during pathogen ingression was limited. These data show that the plant proteinase inhibitors constitute one of the components of the plant defense system that are induced in response to bacterial pathogen invasion. PMID- 1932817 TI - A new technique for intraluminal hollow organ imaging: three-dimensional ultrasound. AB - Intraluminal ultrasound (ILUS) is a new catheter-based system which produces two dimensional (2D), cross-sectional images of tubular structures. The principle of image acquisition using 5.0 Fr (30 MHz) and 8.0 Fr (20 MHz) ILUS catheters containing ultrasound transducers at the tip, is equally applicable to all tubular or hollow organs. This article illustrates the feasibility of intraluminal imaging of hollow organ structures, and describes computerized three dimensional (3D) reconstruction of the 2D images, using a PC-based image analysis system. A set (n = 90) of longitudinally aligned, consecutive 2D images was sampled from various organs (canine bladder, urethra, jejunum, esophagus, and trachea) and computer processed to produce 3D images. By adjusting image density threshold and viewing angle, the lumen and wall morphology can be examined in any projection. Possible applications include diagnosis of lumen encroaching pathology, guidance of intraluminal instruments, and assessment of the effects of endoluminal interventions. PMID- 1932816 TI - Falloposcopic observations of endotubal isthmic plugs as a cause of reversible obstruction and their histological characterization. AB - Eighty falloposcopies were performed in fallopian tubes of women with suspected tubal disease. In three falloposcopies (4%), isthmic plugs were observed occluding the entire isthmic lumen. In all cases these plugs were mobilized by falloposcopic-directed, selected tubal cannulation and aquadissection techniques. Restoration of tubal patency, verified by concurrent chromopertubation under laparoscopic monitoring was achieved in all cases. On one occasion, the isthmic plug was mobilized and identified on the fimbria, and tubal patency was confirmed. When this plug was retrieved and examined histologically, it was found to consist of a cast of debris containing aggregates of histiocyticlike cells of endometrial stromal or mesothelial origin. The genesis of these plugs is unknown. In another subgroup, white to yellow mucus like fragments were observed within the intramural and isthmic lumen during a further 8 of 80 falloposcopies (10%). Whether these mucus like fragments are of physiological or pathophysiological significance remains to be determined. Objective demonstration that isthmic plugs can cause reversible proximal tubal obstruction (PTO) has been achieved using falloposcopy. Falloposcopy offers the diagnostician the ability to objectively classify the cause of PTO. A useful falloposcopic classification and scoring system of tubal lumen lesions has been utilized and is described. PMID- 1932818 TI - Plain film imaging and tomography. PMID- 1932820 TI - Selection of imaging modalities for patients presenting with symptoms of internal derangement. PMID- 1932819 TI - Nuclear medicine imaging. PMID- 1932821 TI - Imaging of the temporomandibular joint in rheumatic disease. PMID- 1932822 TI - Imaging of the temporomandibular joint in juvenile rheumatoid arthritis. PMID- 1932823 TI - Computed tomography. PMID- 1932824 TI - Differential diagnosis of craniofacial pain. PMID- 1932825 TI - Arthrography of the inferior joint space of the temporomandibular joint. PMID- 1932826 TI - Double contrast arthrography. PMID- 1932827 TI - Digital subtraction arthrography. PMID- 1932828 TI - Magnetic resonance imaging. PMID- 1932829 TI - Gastrointestinal bleeding: endoscopic treatment of peptic ulcer haemorrhage. AB - The development and study of haemostatic methods that can be used through flexible endoscopes has been one area of gastroenterology in which major advances have been made over the last 15 years. Bioengineering research with lasers and thermal probes as well as the study and application of simple injection techniques has given the endoscopist a range of tools with which to stop bleeding. Randomized controlled trials have provided fairly convincing evidence that these methods can be of value in the treatment of human peptic ulcer bleeding. PMID- 1932830 TI - True and false large bowel obstruction. AB - Acute large bowel obstruction can be the result of mechanical causes (such as colorectal cancer) or motility disturbances, the latter being termed colonic pseudo-obstruction. Whatever the aetiology, the pathophysiology of large bowel obstruction has clinical significance. Changes in motility augmented by increased colonic blood flow may play a role in dissemination of tumour cells and/or bacteria. Intravascular fluid depletion, especially shortly after intestinal decompression, has important haemodynamic implications. The diagnosis is often confirmed on plain abdominal X-ray, but water-soluble contrast studies are important in distinguishing a mechanical obstruction (which almost always requires an operation) from a pseudo-obstruction (which can usually be managed without surgery). Mortality and morbidity may be reduced by optimization of the patient's condition both before and after the operation using intensive care facilities and by careful timing of surgery. The surgical management of malignant large bowel obstruction is best directed by a senior surgeon. For tumours up to and including the splenic flexure, an extended right hemicolectomy is advisable since it offers adequate removal of the tumour and allows an immediate safe ileocolic anastomosis. More distal tumours should be resected if possible, and there is much to recommend on-table irrigation and immediate anastomosis, although a colostomy with a mucous fistula or Hartmann's procedure still have a place. Endoscopic diagnosis and decompression enables definitive surgery to be undertaken electively and several techniques are being evaluated. Non-operative reduction of sigmoid volvulus by rigid or flexible endoscopy is achieved with high success rates, but is not recommended for caecal volvulus. Resection is usually necessary in both to prevent recurrence. Mortality of colonic volvulus is closely related to bowel viability. Uncomplicated colonic pseudo-obstruction may be managed medically or by endoscopic decompression. It often occurs in association with systemic medical conditions, which need to be treated vigorously. Surgery is indicated if there are signs of impending or frank perforation, or if non-operative measures fail. PMID- 1932831 TI - Intra-abdominal sepsis: the role of radiology. AB - A wide range of imaging tools is available for the investigation of abdominal sepsis. Plain films and barium studies alone are generally regarded as inadequate and most patients will require ultrasound, CT or nuclear medicine studies to locate the source of sepsis. The choice of imaging modality depends on several factors, most important of which are the clinical condition of the patient and the presence or absence of localizing signs and symptoms. Ultrasound has the advantage of being portable and is therefore probably the best initial imaging method for the critically ill patient. It should also be the first investigation in patients with signs and symptoms localizing to the right upper quadrant, renal areas, subphrenic spaces or pelvis. Transvaginal ultrasound is particularly useful in examining the pelvis. CT is the imaging modality of choice for the pancreas and retroperitoneum and in patients who are poor candidates for ultrasound or in whom visualization on ultrasound is inadequate. In patients with PUO or evidence of sepsis without localizing signs or symptoms, nuclear medicine studies in the form of 67Ga citrate or labelled white cell scans are useful to localize the septic focus, although in most cases CT or ultrasound will subsequently be required for detailed anatomical definition. Imaging techniques have an increasingly important role to play in the treatment of sepsis, and guided aspiration and drainage may be performed with a high degree of accuracy under ultrasound or CT guidance, eliminating the need for surgical intervention in many individuals. PMID- 1932832 TI - Intra-abdominal sepsis: the role of surgery. AB - The role of the surgeon in intra-abdominal sepsis is multifactorial. A comprehensive understanding of the incidence and pathophysiology of diseases which cause intra-abdominal sepsis is the key to the diagnosis and treatment of such ailments. In simplest terms, the aetiology has two basic mechanisms: (a) violation of the 'bug-body barrier' and (b) obstruction to the flow of a body fluid with subsequent bacterial overgrowth. Either of these mechanisms may affect any of the organs within the abdomen, leading to sepsis. The peritoneal cavity is a dynamic structure which responds to insults in certain predictable manners which notify the alert physician that danger is present. Recognition of these signs through history and physical examination are the most important aspects of diagnosis. Confirmation of suspicions can be obtained with radiological modalities, but they are not a substitute for clinical judgement. Treatment of intra-abdominal sepsis should always begin with resuscitation and systemic antibiotics. Alleviation of the septic source is mandatory, and this may be achieved either operatively or non-operatively (i.e. percutaneous or endoscopic procedures). When the patient does not improve after the initial procedure, then a missed focus of infection must be investigated. In some cases, a planned or staged second operation may be needed to further debride necrotic tissue. Antibiotics should be of adequate spectrum and bioavailability to kill the species of bacteria most likely to cause the infection. This regimen may be altered when culture and sensitivity reports are completed. Finally, patients whose immune system function has been altered by disease or treatment must be assumed very ill until proven otherwise. These are general guidelines in the management of patients with intra-abdominal sepsis. Individual cases may necessitate slight modifications, but all require a high level of vigilance and expertise in order to combat a very lethal disease. PMID- 1932833 TI - The acute abdomen: the role of computer-assisted diagnosis. AB - CAD has been used in over 20,000 patients in an Accident and Emergency Department. Structured documentation has replaced normal case notes and a patient record is created which includes investigations and management. A copy of the documentation acts as an immediate communication to the general practitioner. The information is held on a computer and is readily accessed to produce feedback and to allow audit of any number of parameters. The results show that an improvement in diagnostic accuracy and a reduction in admissions and unnecessary laparotomies continues over 15 years. Problems have occurred; some are inherent to the system and some have been minimized as a result of a series of studies. The savings in terms of finance and facilities are considerable and the cost is small in comparison as the programs are available and the cost of hardware has diminished. It is concluded that documentation is essential. This allows the more accurate collection of information, permits analysis, acts as a method of communication and creates a detailed patient record. The use of this part of the CADA system produces a considerable improvement in the parameters used to assess satisfactory patient management. The computer diagnostic program produces a higher level of diagnostic accuracy than that obtained by doctors who are not using the system. It does not normally exceed the accuracy of the doctors who are using the structured documentation and entering the information into the computer. Other mathematical models might lead to an improvement, particularly if they were based on the diagnostic process used by a senior clinician. The method of entry of information could be facilitated by modern technology, including light pens or word sensitive computers. This would reduce the time required for completion of the documents. A number of possible improvements in the CADA system are reported and some have been studied in detail with little evidence of significant change. The computer part of the system has an educational value and presents a stimulating challenge to the junior hospital staff seeing the patient for the first time in the Accident and Emergency Department. Rapid feedback is possible and advantageous. Possibly the greatest value of the computer is in the analysis of the value of clinical features in diagnosis, which has not been easy in the past. It has also allowed precise assessment of the value of investigations in the diagnosis of patients with a suspected disease, which leads to more appropriate management and the saving of facilities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1932834 TI - The acute abdomen: the role of peritoneal cytology. PMID- 1932835 TI - [Mortality of cancer around nuclear plants]. PMID- 1932836 TI - [Breast cancer: can tamoxifen, under certain conditions, have adverse effects?]. PMID- 1932837 TI - [Tumor response in comparative trials]. AB - Survival improvement is the main aim of most cancer trials. Tumor response is a very common end-point in this context, as it permits a quick answer. It is useful criterion for screening in phase II trials, but cannot be utilised in phase III comparative trials for several reasons put forward in this article. PMID- 1932838 TI - [Reevaluation of indications for adjuvant hormone therapy in primary breast cancer with high metastatic risk]. AB - This study concerns the correlation between ER and PR status, menopausal status and the effect of adjuvant hormonotherapy in high risk primary breast cancer patients. We have compared the results obtained in a randomized trial (Institut Paoli-Calmettes, Marseille) with those of a historic series (Centre Rene Huguenin, Saint-Cloud). The patients presented the same clinical and histological criteria and received identical therapeutic protocols (chemotherapy and/or hormonotherapy). Compared with patients receiving no adjuvant treatment, it appeared that: 1) in post-menopausal patients, a significant detrimental effect of tamoxifen was found in ER-negative patients, while in ER-positive patients hormonal treatment was well correlated with both the presence and level of steroid receptors; 2) in pre-menopausal patients, hormonal therapy (oophorectomy + tamoxifen) appeared to be mediated by a complex mechanism involving more than an ER-positive cell population. In the light of the published results, the present findings underline the importance of reevaluating the indications of hormonotherapy in terms of hormone receptors and menopausal status. They also indicate the importance of biological factors in the evaluation of response to therapy. They can identify, subsets of patients in whom a given therapeutic protocol is detrimental, even though it may be beneficial for the overall population. heterogeneity in response to therapy among patient subsets is one of the most important problems which confronts medical statisticians and clinical investigators. PMID- 1932839 TI - [Hepatic metastasis of unknown primary site]. AB - In this retrospective study, 91 patients (30%) out of a series of 304 with metastatic cancer of unknown primary site were found to have liver metastases. The liver was the only metastatic site in 28 (31%) cases and was associated with other sites in 63 (69%) cases. Median age was 62 yr in 61 male patients and 59 yr in 30 female patients. Thirty patients were submitted to an extensive investigation in search of the primary tumor, including systematic endoscopies: no primary cancer was found in these patients. In 61 other patients, only symptom oriented investigations were performed and the primary cancer was found in 11 cases. The histologic type was adenocarcinoma in 71 (78%) cases, undifferentiated in 11 (12%) cases, epidermoid in 5 (6%) cases and determined by cytology alone in 4 cases. The median survival was 4 months in patients with metastases in the liver only, and 5 months in the other patients. This difference was not significant, so prognostic factors such as the Karnofsky index, weight loss, CEA and LDH levels were evaluated in the entire group; these factors do not have significant prognostic value. By contrast, when patients were able to receive chemotherapy, median survival was better (4 months) than without (median survival: 1 month; P = 0.005). In addition, in the case of objective response to chemotherapy, the median survival was 9 months versus 3.5 months for patients without objective response (P = 0.001). Seventy-three out of 91 patients (80%) were treated with chemotherapy regimen; 65 patients were evaluable: the objective response rate was 11 +/- 7% (7/65). Different regimens were used. With a non toxic combination of fluorouracil, vinblastine and cyclophosphamide, 3 partial responses greater than or equal to 50% out of 43 patients (7 +/- 8%) were obtained. No significant advantage was observed when adriamycin was added to FU (4/13): 31 +/- 25%. Second- or third line chemotherapy regimen due to progression of the disease after the first-line combination provided only one objective response out of 36 patients. According to this retrospective study we recommend that overinvestigation be avoided in patients, with liver metastases of unknown primary site and that these patients be treated with non-toxic drug combinations. PMID- 1932840 TI - BCM-IMx and CA15.3 serum levels in patients with breast cancer: a comparative study. PMID- 1932841 TI - [Multidisciplinary cooperation. An unusual case of thymoma]. PMID- 1932842 TI - [Immunity and cancer in Brazzaville]. PMID- 1932843 TI - Relevance of major stress events as an indicator of disease activity prevalence in inflammatory bowel disease. AB - The impact of psychological stress in recurrence of inflammatory bowel disease (IBD) is unclear. Why some patients with ulcerative colitis (UC) or Crohn's disease (CD) have unrelenting relapses whereas other IBD patients experience long periods of quiescent disease remains an enigma. The authors examined the risk of exposure to major stress events in clinical episodes of IBD. They followed up on 124 persons in a prospective study that monitored behavioral and biological characteristics for a period of 6 months. Stress-exposed subjects demonstrated increased risk of clinical episodes of disease when compared with unexposed subjects (RR = 2.6, 95% CI: 1.3-4.9). Elevated effect measures were highest for the domain of health-related stress (RR = 3.8, 95% CI: 1.5-9.9). In the multiple regression analysis, major stress events remained the most significant indicator of disease activity in the presence of the covariables considered. Only 7% of the variation in disease activity was uniquely attributed to stress. Baseline activity was the other notable indicator of subsequent disease activity in the study sample. All variables considered together explained 52% of the variance observed and implicated factors of potential clinical importance in monitoring recurrence of the disease. PMID- 1932844 TI - Reliability and validity of the Work-Related Strain Inventory among health professionals. AB - This article provides evidence from five samples of different health professionals (family physicians, emergency medical technicians, hospital nurses, flight nurses, and emergency medicine residents) for the reliability and validity of the Work-Related Strain Inventory (WRSI). The inventory consists of 18 items and was designed to measure perceptions of strain in occupational settings. Internal consistency reliability ranged from .85 to .90 and, as predicted, was correlated with the Maslach Burnout Inventory and measures of depression, role ambiguity, job satisfaction, and work-group functioning. When compared with different measures of depression symptoms (eg, Zung Self-Rating of Depression Scale, Center for Epidemiologic Studies Depression Scale), the Work-Related Strain Inventory was found to measure a different and independent construct. This inventory, a short, easily administered measure with good reliability, may be useful for appraising levels of work-related strain in behavioral and organizational models of the consequences of stress in different work environments. PMID- 1932845 TI - An Inventory of Positive Psychological Attitudes with potential relevance to health outcomes: validation and preliminary testing. AB - This article describes the validation of an Inventory of Positive Psychological Attitudes that has potential relevance to health outcomes and its preliminary testing with chronic pain patients. The inventory taps two attitudinal domains: (1) life purpose and satisfaction and (2) self-confidence during potentially stressful situations. It also provides a total score. The inventory scales, developed using factor analysis, were found to have a strong degree of internal reliability and concurrent validity. Preliminary testing suggested that positive change on these scales correlates with positive changes in the health status of chronic pain patients. Multiple regression analyses suggested that the interactions of these positive psychological attitudes with health status are not fully accounted for by the interactions of negative psychological attitudes with health status. PMID- 1932846 TI - Additional evidence for the relationship between Type A behavior and social support in men. AB - This study examined social support as a mediator of susceptibility to coronary disease in Type A individuals. Sixty-four male subjects completed the Jenkins Activity Survey and the Sarason Social Support Questionnaire. The correlations between Type A scores, the speed and impatience and hard-driving competitiveness factors of the Jenkins survey, and Sarason's social support were found to be negative, which was contrary to earlier findings. The authors hypothesize that these differing results may be a function of age and environment. Finally, and pertinent to the mechanism by which social support may be associated with coronary heart disease, systolic blood pressure was negatively correlated to satisfaction with social support. PMID- 1932847 TI - The influence on blood pressure during daily activities of a single session of aerobic exercise. AB - Previous research has examined the effectiveness of a single session of aerobic exercise in lowering blood pressure responsivity to the subsequent presentation of a nonexercise stressor in the laboratory. This case study was designed to explore the possibility that a single session of aerobic exercise might lower blood pressure for up to 4 hours postexercise as the subject engaged in his usual activities at home and at work. The subject was an untrained, unmedicated, borderline hypertensive who underwent ambulatory blood pressure monitoring as he maintained a normal schedule of activities over a 5-day period. On 2 of the 5 days, the subject exercised at 8:30 AM for 30 minutes at 70% VO2max. Blood pressure readings on days when the subject read for 30 minutes were compared with readings on days when he exercised. He showed an average reduction in systolic blood pressure of 26.4 mm Hg at 2 hours after exercise, 24.2 mm Hg at 4 hours afterward, and 12.2 mm Hg at 9 hours after the exercise. Changes in diastolic blood pressure and heart rate were smaller and less consistent. The authors concluded that the modifying influence of a single session of aerobic exercise on blood pressure responsivity to subsequent laboratory-based stressors may also extend to the natural environment. The discussion addresses theoretical, methodological, and clinical considerations in the use of aerobic exercise to modify excessive blood pressure reactivity. PMID- 1932849 TI - Propachlor and N-isopropylaniline residues in onions (Allium cepa) and muck soils. PMID- 1932848 TI - Effects of ozonation on mutagenic activity of polycyclic aromatic hydrocarbons. PMID- 1932850 TI - Effect of added reactive aluminum on aldicarb adsorption by a high organic soil. PMID- 1932851 TI - Levels of volatile N-nitrosamines in baby bottle rubber nipples commercialized in Belo Horizonte, Mina Gerais, Brazil. PMID- 1932852 TI - Organochlorines in crocodile eggs from Kenya. PMID- 1932853 TI - Bensulfuron methyl dissipation in California rice fields, and residue levels in agricultural drains and the Sacramento River. PMID- 1932854 TI - Cadmium content of Cameroonian cigarettes: comparison with other foreign brands sold in Cameroon. PMID- 1932855 TI - Survey of farm wells for nutrients and minerals, Ontario, Canada, 1986 and 1987. PMID- 1932856 TI - Effect of an addition of sodium sulfite on the mutagenicity of chlorinated solutions of aquatic humic substances. PMID- 1932857 TI - Effects of physical binding of o-Nitroanisole with feed upon its systemic availability in male F344 rats. PMID- 1932858 TI - Effect of cadmium-mobilizing dithiocarbamates on essential trace metal metabolism in rats. PMID- 1932859 TI - Decline of citrus due to presence of landfill gases in the soil. PMID- 1932860 TI - O-dealkylation of resorufin ethers as an indicator of hepatic cytochrome P-450 isoenzyme induction in the cotton rat (Sigmodon hispidus): a method for monitoring environmental contamination. PMID- 1932861 TI - Impact of an organophosphate herbicide (Glyphosate) on periphyton communities developed in experimental streams. PMID- 1932862 TI - Effects of a Diazinon formulation on unialgal growth rates and phytoplankton diversity. PMID- 1932863 TI - Growth, chlorophyll a content, nitrogen-fixing ability, and certain metabolic activities of Nostoc muscorum: effect of methylparathion and benthiocarb. PMID- 1932864 TI - Toxic effect of parathion on Moina macrocopa metabolism. PMID- 1932865 TI - Comparative toxicity and structure-activity in Chlorella and Tetrahymena: monosubstituted phenols. PMID- 1932866 TI - Effect of oil-contaminated sediment on the longhorn sculpin (Myoxocephalus octodecemspinosus) following chronic exposure. PMID- 1932867 TI - Cadmium uptake from cadmium-spiked sediments by four freshwater invertebrates. PMID- 1932868 TI - Reproductive value and the cost of reproduction in Daphnia carinata and Echinisca triserialis (Crustacea: Cladocera) exposed to food and cadmium stress. PMID- 1932869 TI - Effect of pH and temperature on the uptake of cadmium by Lemna minor L. PMID- 1932870 TI - Comparative study of cadmium and lead accumulations in Cambarus bartoni (Fab.) (Decapoda, Crustacea) from an acidic and neutral lake. PMID- 1932871 TI - Interactive effects of the fungicide chlorothalonil and the herbicide metribuzin towards the fungal pathogen Alternaria solani. PMID- 1932872 TI - [Facial aging. The evolution of the soft tissues]. AB - Ageing of the face is one of the most apparent. Face varies in shape and aspect. The reasons of these modifications are various: skin ageing, lost of teeth, changes in facial skeleton and modifications of the whole facial soft tissues. Soft tissues evolution in mentalis and anterior nasal spin regions was studied on a 206, 21 to 101 years old subjects population. It was shown that in both men and women samples the soft tissues thickness increase in the mentalis region and decrease in that of anterior nasal spin. PMID- 1932873 TI - [Lingual status and mandibular morphology]. AB - Is the balance of the hyo-lingual musculature very important about mandibular morphology and orientation of mandibular growth? The purpose of this study is to detect the existence of possible reports between hyo-lingual position and mandibular morphogenesis. The selected population is made of fifty children from eight and a half to ten and a half years old, who are thumb sucking and mouth breathing. The means of study are norma lateralis teleradiographs made when facial musculature is at rest position. The statistical analysis implies a descriptive and correlative analysis of 82 variables, and a comparative study with an other sample. In spite of anatomic bonds, it seems to be a relative independence between lingual morphology and orientation of mandibular growth. Perhaps head posture is it a more important mechanism! PMID- 1932874 TI - [An ultrastructural study of the fibrillary component of dental tissues]. AB - The recent interest for highly sophisticated techniques of dental tissue preparation aiming to display very particular structures, moved the AA. to improve the literature suggestions. In particular they made TEM and SEM observations of transitional zones between healthy and normal pulp and dentin after decalcification and trypsin at different concentrations treatment. The images obtained draw in the attention the study facilities of a technique that really removes all the non collagenic material. The data obtained in the pericellular zones also allowed some interventions in the recent literature discussion about inter-odontoblastic fibres. PMID- 1932875 TI - [Guided tissue regeneration: an ultrastructural observation by transmission electron microscopy and scanning electron microscopy]. AB - PTFE membranes are used for guided tissue regeneration in order to treat angular bone defects or forcation involvements in surgical treatment. Ultrastructural investigations have been performed by means of electron transmission and scanning microscopy. In agreement with previous reports, fibroblast cells adhering to the reticular structure of PTFE membrane were observed; these were interposed among coagulated clusters of fibrinous material and blood cells round shaped. Elongated bacterial cells were always present in the microscope fields analysed. These observations were confirmed by means of transmission microscopy; moreover specific techniques enabled us to demonstrate that fibroblast cells were synthetizing collagen, which was present in the form of extracellular fibers mixed to fibrin clusters. Roundish and elongate bacterial cells were always observed both in the extracellular matrix and into macrophages. PMID- 1932876 TI - Volatile solvent abuse and 963 deaths. PMID- 1932877 TI - Abstaining for foetal health: the fiction that even light drinking is dangerous. AB - There is a strong ideological and political movement in the USA to convince pregnant women not to drink any alcohol. An examination of the research literature on the results of drinking during pregnancy does not provide any evidence that light drinking is harmful to the foetus. The chief defects in the research that make conclusions about the effects of 'moderate' or 'light' drinking invalid are the ways in which drinking patterns are categorized: a) usually the categories used are 'average per day', the different effects of binging and light drinking being thus confused; b) often the heaviest drinking category is described as 'two or more drinks a day', sometimes even 'one or more'. Obviously, one cannot tell whether any instances of foetal damage occurring in that group came from women who drank only two drinks each day, which would be light drinking, or from those who drank ten drinks each day since 'ten drinks a day' is part of the category 'two or more'. PMID- 1932878 TI - Cannabis psychosis following bhang ingestion. AB - The purpose of this preliminary investigation is to systematically characterize the signs and symptoms of cannabis psychosis in individuals who presented for psychiatric treatment in Pakistan after ingestion of bhang; a beverage containing cannabis. In order to control for the behavioral effects of cannabis alone, symptoms produced by bhang ingestion among non-patients consuming the same beverage were compared with those symptoms found among psychotic patients. Patients differed from controls in that a higher proportion of patients were found to be chronic users of bhang, and had a past history of psychotic episodes. Presenting symptoms of bhang-induced psychosis found in patients included grandiosity, excitement, hostility, uncooperativeness, disorientation, hallucinatory behavior and unusual thought content. Neuroleptic treatment successfully attenuated psychotic symptoms within five days of the initiation of the episode. The presenting symptoms of bhang-induced psychosis are consistent with a brief mania-like disorder with paranoid psychotic features, and cognitive dysfunction. Several etiologic hypotheses are proposed. PMID- 1932879 TI - Sexual lifestyles in injecting drug users in Italy: potential for HIV infection transmission. First Multicentre Study Group. AB - To better target efforts aimed at modifying sexual behaviour among injecting drug users (IDUs), we conducted a detailed analysis of sexual partners and practices reported by 1214 Italian heterosexual drug users during the period June 1985-June 1987. Females were more likely to have only drug-using partners (42.8% vs 17.1%), while males were more likely to have only non drug-using partners (50.5% vs 21.4%). Female drug users were more likely to report either one partner or greater than 10 partners, while males were more likely to report 2-10 partners. Nearly 90% of women with only drug-using partners had only one partner. Overall, 29% of women with only non drug-using partners reported that they always used condoms. This proportion increased to 65% among women with greater than 10 non drug-using partners. In Italy, male IDUs may play a greater role than female IDUs in sexual transmission of HIV infection to the heterosexual non drug-using partners. PMID- 1932880 TI - Changes over time in heroin and cocaine use among injecting drug users in Amsterdam, The Netherlands, 1985-1989. AB - Three hundred and eighty six injecting drug users entered into an HIV study through methadone programs over a 40 month period. Differences in oral, intranasal and parenteral use of heroin and cocaine were assessed between four consecutive 10 month intake groups. Heroin smoking and cocaine freebasing were increased in the later intake groups, while there were no significant changes in injecting variables. No relationship between sexual risk behaviour and cocaine freebasing was found. HIV seropositivity was less among cocaine freebasers at 19% compared to 32% among non freebasers. The increase in heroin smoking and cocaine freebasing may have a favourable preventive effect on the spread of HIV among this high risk group. PMID- 1932881 TI - The impact of school-based drug education. AB - Outcome evaluation of the impact of drug education on a representative sample of 1197 pupils revealed no effects of drug education on drug-related behaviour or drug-related attitudes. However, drug education raised levels of drug-related knowledge. The long term implications of these findings would require further study. Comparison of process and outcome measures indicated that, with the exception of knowledge, teachers' positive views of drug education were misplaced. Critical aspects of good practice are discussed, both at the level of the individual teacher and in terms of whole-school factors. PMID- 1932882 TI - Locus of control of behaviour: is high externality associated with substance misuse? AB - Personal control and responsibility are key themes in the therapeutic use of 'motivational interviewing'. This popular method of counselling has suggested that clients need to believe they have a significant degree of control over their behaviour if they are to make progress. Using a well validated psychological test on locus of control of behaviour, our research sought to establish whether active misusers really believed they had less personal control than non-misusers. To establish this a sample of misusers was tested and compared with three diverse, comparable groups. Possible confounding factors such as age, sex and class were controlled for. T tests established a significant difference between the active misusers and the other sampled groups. Further, a regression analysis of variance, calculated to explain the differing external scores offered no reasonable explanation as far as age, sex and class were concerned. Alternatively, self diagnosed substance misuse accounted for 23% of the variation in scores. We concluded, therefore, that high externality scores are a good indicator of active misusing behaviour and that beliefs about personal control are important to address, if one is to increase the chances of a positive client outcome. PMID- 1932883 TI - The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. AB - We examine and refine the Fagerstrom Tolerance Questionnaire (FTQ: Fagerstrom, 1978). The relation between each FTQ item and biochemical measures of heaviness of smoking was examined in 254 smokers. We found that the nicotine rating item and the inhalation item were unrelated to any of our biochemical measures and these two items were primary contributors to psychometric deficiencies in the FTQ. We also found that a revised scoring of time to the first cigarette of the day (TTF) and number of cigarettes smoked per day (CPD) improved the scale. We present a revision of the FTQ: the Fagerstrom Test for Nicotine Dependence (FTND). PMID- 1932884 TI - Some body-related attitudes in women smokers and non-smokers. AB - The body-related attitudes of female current, ex, and never-smokers were compared using a new questionnaire that assesses a wide range of attitudes towards the body. In a population survey, current smokers felt less attractive than those women who had never smoked, but they did not experience themselves as being less strong and fit than the non-smokers. There were no significant inter relationships of smoking status, attitudes and body weight. The implications of these observations for anti-smoking campaigns are briefly discussed. PMID- 1932885 TI - Interpersonal versus technological orientations and alcohol abuse in future physicians. AB - Etiologic research on alcohol-related impairment in physicians has elucidated various risk factors including family history of alcoholism, symptomatic distress, personality deficits, and high academic achievement. This study of medical students points to the additional salience of future practice orientations involving technological/status versus interpersonal concerns. A cohort of students was surveyed at medical school entrance and again in the second training year. Alcohol abusers (particularly medical school onset cases) manifested significantly higher technological/status and lower interpersonal concerns compared to non-abusers. Differences across future specialty choices were also found. However, additional longitudinal research is necessary to clarify the causal directionality of these relationships. PMID- 1932886 TI - Functioning, life context, and help-seeking among late-onset problem drinkers: comparisons with nonproblem and early-onset problem drinkers. AB - We compared the functioning and life contexts of late-middle-aged adults classified as late-onset problem drinkers (n = 229), early-onset problem drinkers (n = 475), and nonproblem drinkers (n = 609). Compared with nonproblem drinkers, late-onset problem drinkers consumed more alcohol and functioned more poorly; they also reported more negative life events and chronic stressors, fewer social resources, and more use of avoidance coping. However, late-onset problem drinkers consumed less alcohol, had fewer drinking problems, functioned better, and had more benign life contexts than did early-onset problem drinkers. We found no evidence of an association between age-related loss events and the onset of late life drinking problems. Very few problem drinkers sought help specifically for their alcohol abuse, but about 25% did seek treatment from mental health practitioners. Problem drinkers who were functioning more poorly and who reported more life stressors and fewer social resources were more likely to seek help. PMID- 1932888 TI - Brazil. PMID- 1932887 TI - A six country survey of the content and structure of heroin treatment programmes using methadone. AB - The use of methadone in the treatment of drug dependence has provoked a good deal of controversy. However, it is clear that there is considerable variation between methadone treatment programmes and relatively little detail is available about the organization and operation of these programmes. This World Health Organization survey examines the content and structure of methadone treatment programmes, and particularly methadone maintenance programmes, in six countries. The six countries were Australia, Canada, France, the Netherlands, Thailand and the UK. The report presents information about the extent of national problems and about such issues as type of dispensing practices, dose- and time-limits for prescribing methadone, programme entry criteria, staffing, integration with other services, and urine testing. Developments and trends during the decade 1980-1990 are discussed and implications for further research and programme development are presented. PMID- 1932889 TI - New York City prisons. PMID- 1932890 TI - Prisons and HIV. PMID- 1932891 TI - Skeletal response of ovariectomized rats to low and high doses of 17 beta estradiol. AB - Recent studies indicate that the mode of action of estrogen in preventing bone loss due to ovarian hormone deficiency may vary with the dose of the hormone. In this study four groups of ovariectomized animals were maintained on a wide range of doses of 17 beta-estradiol to further determine the relationship of dose to the mechanism by which estrogen prevents ovarian hormone deficiency bone loss. Ovariectomy caused a significant decrease in bone density and cancellous bone volume at the proximal metaphysis of the tibia. The decrease was prevented in a dose-dependent manner by estradiol. The rate of bone apposition in cancellous bone in the proximal tibia was increased by ovariectomy, and inhibited in a dose dependent manner by estradiol. Similarly, ovariectomy increased the excretion of urinary hydroxyproline, an index of the rate of bone turnover, and serum alkaline and tartrate-resistant acid phosphatase. The increases were prevented in a dose dependent manner by estradiol. In addition, the very high dose of estradiol, but not the lower doses, caused a marked (50%) decrease in serum osteocalcin. Our interpretation of these findings is that the low to very high doses of estradiol used in this study decreased the progression of the bone loss due to ovariectomy by suppression of the rate of bone turnover that involved the depression of both osteoclastic resorption and osteoblastic bone formation. PMID- 1932893 TI - Effects of estrogen and tamoxifen on serum osteocalcin levels in ovariectomized rats. AB - Serum osteocalcin levels were measured in ovariectomized rats treated for 35 days with either estrogens (ethynylestradiol administered orally or 17 beta-estradiol administered by subcutaneous injection) or the antiestrogenic compound tamoxifen (administered both orally and subcutaneously). Tamoxifen is a non-steroidal compound that has mixed agonist/antagonist actions in several biological models, but is commonly referred to as an 'antiestrogen'. Administration of tamoxifen, like estrogen, caused a reduction in the increases in animal body weight and femur length during the test period, and greater bone density in the distal femur metaphysis compared to ovariectomized control animals. Both the estrogens and tamoxifen caused a dose-dependent decrease in serum osteocalcin as compared to the levels in the serum of ovariectomized control rats; however, tamoxifen displayed both reduced potency and efficacy compared to estrogens. Serum osteocalcin levels declined in a linear fashion throughout the estrogen dose range, and at the highest doses tested (400 micrograms/kg/d ethynylestradiol; 100 micrograms/kg/d 17 beta-estradiol), osteocalcin levels were reduced by 45-50% compared to those found in ovariectomized control animals. The reduction in serum osteocalcin concentrations in tamoxifen-treated animals, on the other hand, was reduced maximally by about 30% compared to those found in the ovariectomized controls at a dose of 100 micrograms/kg/d. Further reduction in serum osteocalcin beyond this level was not observed with increasing doses of tamoxifen. We conclude that tamoxifen acts as an estrogen agonist with respect to effects on serum osteocalcin levels, but fails to reduce serum levels of osteocalcin to the extent observed with steroidal estrogens. PMID- 1932892 TI - Regulation of the production of plasminogen activators by bone resorption enhancing and inhibiting factors in three types of osteoblast-like cells. AB - Production of proteolytic enzymes by osteoblasts is considered to be important for the initiation of osteoclastic bone resorption. We examined the production of tissue-type (tPA) and urokinase-type plasminogen activator (uPA) activity by three types of osteoblast-like cells (normal rat osteoblasts, rat and human osteosarcoma cells) using a quantitative spectrophotometric assay and a qualitative gel overlay technique. All 3 types of cells released both types of PA activity into the medium, but normal rat osteoblasts released uPA probably in an inactive form. Treatment with different concentrations of the bone resorbing factors bovine Parathyroid Hormone [1-84], synthetic human Parathyroid Hormone Like Protein [1-34]. Prostaglandin E2, Interleukin-1 beta, Tumor Necrosis Factor alpha and 1,25-dihydroxyvitamin D3 increased in general the production of both PA's by all three cell types. However, there were differences in the relative potencies of these factors. In contrast, Transforming Growth Factor beta, which inhibits bone resorption, decreased PA-activity in osteoblast-like cells. In all three types of cells, under control as well as under stimulated conditions, a high molecular weight form of PA was demonstrated by the gel overlay technique, most likely a complex of tPA with the PA-inhibitor PAI-1. The uniform increase in production of PA's by osteoblast-like cells in response to bone resorbing factors and its decrease by TGF beta supports the notion that PA's are involved in bone resorption. The exact mechanism however, remains to be elucidated. PMID- 1932894 TI - Osteoclast growth factor activity in medium conditioned by fetal rat bones. AB - The presence and biological activity of an Osteoclast Growth Factor (OGF) was investigated in serum-free medium conditioned by periostless fetal rat calvaria in culture. OGF activity was assessed using in vitro systems of fetal rat long bones and adult rat bone marrow cells. Rat calvaria conditioned medium (RCCM) increased the number of osteoclasts in the long bone cultures, partly due to stimulation of progenitor proliferation. RCCM did not exert a direct bone resorbing activity (45Calcium release assay) on the pre-existing osteoclasts residing in the long bones, but stimulated bone resorption in long term cultures, apparently in an indirect manner by enhancing the number of osteoclasts. In cultures of bone marrow cells isolated from adult rats, RCCM markedly stimulated the formation of mononuclear cells which were positively stained for tartrate resistant acid phosphatase (TRAP). The osteoclastic nature of the cells was confirmed by specific labeling with 125I-calcitonin. Formation of the TRAP positive cells was significantly inhibited by salmon calcitonin. CM from fetal rat skin cultures did not display a significant OGF activity. Furthermore, unlike the bone marrow cells, peritoneal macrophages did not respond to RCCM and remained devoid of TRAP activity. Neutralization experiments with a specific antibody to GM-CSF indicated that OGF activity in the RCCM could not be ascribed to this hemopoietic growth factor. Secretion of OGF activity was mainly dependent on protein synthesis as addition of cycloheximide to the calvaria cultures significantly inhibited the secretion of OGF into the medium. G3000 HPLC fractionation of RCCM revealed two major OGF peaks with Mr 14,000 and 70,000. Two subsequent reverse-phase HPLC steps using the lower Mr OGF fraction led to a highly purified OGF fraction. The results of this study further provide evidence that bone tissue produces factor(s) which specifically govern the process of osteoclast development, thus providing information about one of the mechanisms controlling bone resorption. PMID- 1932895 TI - How to pay for expensive drugs. PMID- 1932896 TI - More macrolides. PMID- 1932898 TI - Registers for occupational diseases. PMID- 1932897 TI - Fibrinogen. PMID- 1932899 TI - Preventing unwanted pregnancies. PMID- 1932900 TI - Fibrinogen and lipid concentrations as risk factors for transient ischaemic attacks and minor ischaemic strokes. AB - OBJECTIVES: To determine whether fibrinogen and lipid concentrations are risk factors for ischaemic stroke. DESIGN: Case-control study with a population based comparison within the overall study. SETTING: Oxfordshire community stroke project and a neurology clinic. SUBJECTS: 105 patients who had a transient ischaemic attack or minor ischaemic stroke and 352 randomly chosen controls matched for age and sex from the same general practitioners as the incident cases. 52 controls were ineligible or refused interview. 104 cases and 241 controls gave blood samples for analysis. MAIN OUTCOME MEASURES: Response to structured questionnaire, height, weight, blood pressure, and serum concentrations of fibrinogen and lipids. RESULTS: Adjusted for other variables, odds ratios of ischaemic stroke were 1.78 (95% confidence interval 0.91 to 3.48; p = 0.09) [corrected] for fibrinogen concentrations greater than 3.6 g/l; 1.73 (0.90 to 3.29; p = 0.09) [corrected] for total cholesterol concentrations greater than 6.0 mmol/l; 1.34 (0.69 to 2.61; p greater than 0.4) for low density lipoprotein cholesterol concentrations greater than 3.5 mmol/l; and 0.32 (0.15 to 0.69; p = 0.002) for high density lipoprotein cholesterol concentration greater than 1.2 mmol/l. Similar results emerged comparing only community derived cases with transient ischaemic attacks and controls. The effects of fibrinogen, total cholesterol, and high density lipoprotein cholesterol were significant in a test of trend after adjusting for all other variables in the study (chi 2 = 4.14, p less than 0.05; chi 2 = 4.31, p less than 0.05, and chi 2 = 12.15, p greater than 0.001, respectively). History of ischaemic heart disease and hypertension were the only other variables that showed significance, though both lost significance after adjustment (2.06, p = 0.08 and 1.53, p = 0.2, respectively). CONCLUSIONS: Fibrinogen and lipids are important risk factors for ischaemic stroke. The pattern of changes mirrors that found in ischaemic heart disease. PMID- 1932901 TI - Informed consent: study of quality of information given to participants in a clinical trial. AB - OBJECTIVE: To determine whether the participants in a clinical trial had perceived adequate information about the trial according to the guidelines of the Declaration of Helsinki. DESIGN: About 18 months after the end of a gynaecological clinical trial the participants received a questionnaire by post, which focused on the quality of the information given to them before entering the trial. Neither researchers nor participants were aware in advance that the trial would become the subject of this follow up investigation. SETTING: Eight different centres in Sweden. SUBJECTS: 43 women out of the 53 who completed the trial (mean (range) age 23 (16 to 35) years) returned the questionnaire. MAIN OUTCOME MEASURES: Adequacy of the information (based on requirements of the Declaration of Helsinki) to enable the following: understanding of the aims of the study; awareness of what participation meant; and awareness of the possibility of withdrawing from participation at any time. Motives for agreeing to participate, and a subjective evaluation of the given information were also recorded. RESULTS: All but one of the participants had been aware that they were taking part in a research project. Five women stated that they had not been aware that a second laparoscopy was performed only for research reasons. Seven women reported that they had not been aware of the meaning of participating in the project and 17 that they had had no information about the possibility of withdrawing from the study whenever they wanted. In the subjective rating 22 women considered the information given as good or very good. There was a systematic variation in the quality of the given information among the eight centres. CONCLUSION: Although all but one of the participants had been aware that they were taking part in a clinical trial, the quality of the information understood and recalled by participants varied, and in many cases clearly did not meet the guidelines of the Declaration of Helsinki. Variations among centres in participants' perception of information suggest that deficiencies in perception may be caused by informers rather than the participants. PMID- 1932902 TI - Risk of severe hypoglycaemia in insulin treated diabetic patients transferred to human insulin: a case control study. AB - OBJECTIVE: To examine whether transfer from animal insulin to human insulin is associated with an increased risk of severe hypoglycaemia. DESIGN: Matched case control study of insulin treated diabetic patients admitted to hospital because of hypoglycaemia during 1984-7, the period when human insulin was introduced into treatment. SETTING: Case admissions and control admissions were obtained from eight public hospitals within the Swiss canton of Berne and a second control group comprised members of the Bernese section of the Swiss Diabetes Association. SUBJECTS: 94 patients with insulin treated diabetes with a total of 112 admissions for hypoglycaemia during 1984-7 (case admissions), 182 patients with insulin treated diabetes seen in the same hospitals for reasons other than hypoglycaemia with a total of 225 admissions (control admissions), and 86 insulin treated diabetic patients who were members of the Bernese section of the Swiss Diabetes Association. MAIN OUTCOME MEASURES: Type of insulin used at time of admission, glycaemic control as measured by amount of glycated haemoglobin or glucose concentration; severity of hypoglycaemia. RESULTS: Treatment with human insulin at admission was more common in cases than controls (52/112 (46%) admissions v 77/225 (34%); p = 0.003). 116 out of 129 (90%) of admissions taking human insulin had been transferred from animal insulin, mainly because of non availability of porcine insulins. The ratio of rate of hypoglycaemia in those taking human insulin to the rate in those taking animal insulin was 2.4 (95% confidence interval 1.3 to 4.4). Other risk factors for hypoglycaemia were a history of hypoglycaemic coma (rate ratio of history to no history 3.8, 2.3 to 6.4) and good glycaemic control (rate ratio of good to poor control 3.9, 1.4 to 7.5). With multivariate analysis the increase in rate ratio associated with use of human insulin rose to 3.0 (1.4 to 6.4). Comparison with the diabetes association controls also showed an increased risk associated with use of human insulin (2.2; 1.1 to 4.8). CONCLUSIONS: Transfer of treatment from animal insulin to human insulin was associated with an increased risk of severe hypoglycaemia. Caution should be exercised when transferring diabetic patients to human insulin. Further studies are required to elucidate why this effect occurs. PMID- 1932904 TI - Influence of posture and reference point on central venous pressure measurement. PMID- 1932903 TI - Influence of human insulin on symptoms and awareness of hypoglycaemia: a randomised double blind crossover trial. AB - OBJECTIVE: To investigate the apparent increased risk of severe hypoglycaemia associated with use of human insulin by comparing the pattern of symptoms of hypoglycaemia with human insulin and porcine insulin. DESIGN: Randomised controlled double blind crossover trial of treatment with human insulin and porcine insulin, with two treatment periods of six weeks. SETTING: Diabetes outpatient department of a university teaching hospital in Berne, Switzerland. PATIENTS: 44 patients (25 men, 19 women) aged 14 to 60 years, with insulin dependent diabetes mellitus. All patients met the following criteria: receiving treatment with fast acting soluble insulin and long acting protamine insulin; performing multiple daily fingerstick blood glucose self measurements; and had stable glycaemic control with about one mild hypoglycaemic episode a week during the preceding two months. INTERVENTION: Patients were randomised to receive either human or porcine insulin for six weeks and were then changed over to the other type of insulin for a further six weeks. MAIN OUTCOME MEASURE: Questionnaire recording "autonomic" and "neuroglycopenic" symptoms that occurred during hypoglycaemic episodes confirmed by a blood glucose concentration less than or equal to 2.8 mmol/l. RESULTS: Insulin doses and blood glucose, glycated haemoglobin A1c, and fructosamine concentrations were similar during the two treatment periods. 493 questionnaires on hypoglycaemia (234 during treatment with human insulin and 259 during treatment with porcine insulin) were analysed. With human insulin patients were more likely to report lack of concentration (52% v 35%, p = 0.0003) and restlessness (53% v 45%, p = 0.004) and less likely to report hunger (33% v 42%, p = 0.016) than during treatment with porcine insulin. The difference in the pattern of symptoms during the two treatments was similar to that between the 12 patients with a history of recurrent hypoglycaemic coma and the 32 patients without such a history. CONCLUSIONS: The pattern of symptoms associated with human insulin could impair patients' ability to take appropriate steps to avoid severe hypoglycaemia. Caution should be exercised when transferring patients from animal insulin to human insulin, and a large scale randomised trial of the two types of insulin may be justified. PMID- 1932905 TI - Pneumothorax: a complication of fine needle aspiration of the breast. PMID- 1932906 TI - Who is your general practitioner? PMID- 1932907 TI - Adolescent self harm patients: audit of assessment in an accident and emergency department. AB - OBJECTIVE: To examine the assessment of adolescent self harm patients attending an accident and emergency department. DESIGN: Retrospective assessment of case notes. SETTING: Accident and emergency department, Leicester Royal Infirmary. PATIENTS: 210 adolescent patients (aged 9-19 years) attending the department during 1 January 1989-31 December 1989 after deliberate self poisoning; records were available for 200. MAIN OUTCOME MEASURES: Numbers of admissions, discharges from department without either a psychiatric consultation or some form of follow up, and discharges with either of these; scoring of adequacy of psychiatric and social assessment by accident and emergency doctor. RESULTS: 89 patients were admitted (mean score 5.1, excluding 22 patients too drowsy or unforthcoming for proper assessment), 80 were discharged without specific psychiatric consultation or other follow up (mean score 5.4), and 31 were discharged with psychiatric consultation or other follow up (mean score 9.1). The percentage of patients in each group whose assessment by the accident and emergency doctor was considered to be adequate or better than adequate over 10 headings ranged from 0%-40% for admitted patients, 0%-50% for those discharged without psychiatric assessment, and 0%-61% in the remaining group. Overall, in almost half (49%, 54/111) of all of those discharged documentation of the suicidal state was inadequate. CONCLUSION: The assessment of many adolescent self harm patients in this clinic was unsatisfactory. IMPLICATIONS: Doctors working in accident and emergency departments should be encouraged to liaise with child psychiatrists before discharging such patients. PMID- 1932908 TI - Audit officers: what are they up to? PMID- 1932909 TI - High potency factor VIII concentrates: value not proved? PMID- 1932910 TI - Guidelines for the management of convulsions with fever. Joint Working Group of the Research Unit of the Royal College of Physicians and the British Paediatric Association. PMID- 1932911 TI - Strategy for stroke. PMID- 1932912 TI - Communicable diseases other than AIDS. PMID- 1932913 TI - Withdrawing antihypertensive treatment. PMID- 1932914 TI - Effect of a fetal surveillance unit. PMID- 1932915 TI - Alcohol consumption during pregnancy and infants' development. PMID- 1932916 TI - Kala-azar in France. PMID- 1932917 TI - Leprosy in reaction. PMID- 1932918 TI - Papaveretum in women of childbearing potential. PMID- 1932919 TI - Dog bites to children. PMID- 1932920 TI - Accelerated immunisation with diphtheria-tetanus-pertussis vaccine. PMID- 1932921 TI - What do they want? PMID- 1932923 TI - Environmentally acceptable containers for soft drinks. PMID- 1932922 TI - Interpractice collaboration for functional assessment in the elderly. PMID- 1932924 TI - Junior doctors' hours. PMID- 1932925 TI - Completing the feedback loop. PMID- 1932926 TI - Anosmia due to nasal administration of corticosteroid. PMID- 1932927 TI - Carbamazepine and spina bifida. PMID- 1932928 TI - Angioplasty and restenosis. PMID- 1932929 TI - Addressing the most important preventable cause of death. PMID- 1932930 TI - Women in general practice. PMID- 1932931 TI - WIST-ful thinking. PMID- 1932932 TI - Parkinson's disease as community health problem: study in Norwegian nursing homes. The Norwegian Study Group of Parkinson's Disease in the Elderly. AB - OBJECTIVE: To examine the extent of under-diagnosis and overdiagnosis of Parkinson's disease and to determine quality of treatment in a defined population. DESIGN: Clinical evaluation of an elderly population. SETTING: 40 Norwegian nursing homes. SUBJECTS: 3322 residents of nursing homes, of whom 500 were selected by nursing staff for evaluation on the basis of a structured information programme on Parkinson's disease and 269 were examined in detail by neurologists. MAIN OUTCOME MEASURES: Patients' scores on clinical rating scales, diagnosis of parkinsonism, and effect of changing drug treatment. RESULTS: 169 (5.1%) patients were found to have clinical idiopathic Parkinson's disease, 31 of whom had not had the disease diagnosed previously. In addition, 31 patients without the disease were taking antiparkinsonian drugs unnecessarily. Eighty patients were judged to be receiving "optimal" treatment. In the remaining 58, the treatment was changed, and 36 patients showed a definite functional improvement after a 12 week observation period. CONCLUSIONS: The quality of life of many elderly patients with Parkinson's disease could be improved by increasing medical and neurological services. PMID- 1932933 TI - The Dundee coronary risk-disk for management of change in risk factors. AB - OBJECTIVE: To devise a simplified system for grading and monitoring modifiable coronary risk in primary care, to be used with an action plan. METHODS: The risk equation came from 5203 men aged 40-59 in the United Kingdom heart disease prevention project, who had 331 coronary events over five years; the population rank (reading 1-100) was obtained by scoring 10,359 participants in the Scottish heart health study. Calculation of rank was embodied in the Dundee coronary risk disk; the formula was tested against the Whitehall study; disk and action plan were evaluated in primary care. RESULTS: The system measures modifiable coronary risk from smoking, blood pressure, and blood cholesterol concentration by a sex and age related rank running from 1 (high risk, priority action) to 100 (low risk, general advice). The formula predicted outcome acceptably in the Whitehall study and is built into a circular slide rule. Only eight (11%) of 76 general practitioners and practice nurses surveyed already used risk factor scores. After evaluation most thought they should use one and proposed to incorporate the Dundee coronary risk-disk and the associated action plan into their routines. CONCLUSION: The Dundee coronary risk-disk readout of Dundee rank, standardised on a scale of 1 to 100 by age and sex, is a simple, valid means of assessing and monitoring modifiable coronary risk. It puts single risk factors (such as cholesterol concentration) in perspective and can aid selective testing. Understood by medical staff and patients, it should improve the efficiency and effectiveness of the high risk approach to coronary prevention. PMID- 1932934 TI - An action plan for preventing coronary heart disease in primary care. Working Group of the Coronary Prevention Group and the British Heart Foundation. PMID- 1932935 TI - Unemployment rates: an alternative to the Jarman index? AB - OBJECTIVE: To compare the Jarman index with alternative deprivation measures with regard to its usefulness to district health authorities as an indicator of need at small area level. DESIGN: The Jarman index (UPA (8)), Townsend's index of material deprivation, the Scottish Development Department's index, the Department of the Environment's basic index, and unemployment rates were compared in respect of their correlation with measures of morbidity by electoral ward in a typical English district health authority. Measures of morbidity comprised standardised mortality ratios, admission rates (standardised and non-standardised), and permanent sickness rates. Spearman rank correlation coefficients were calculated for each combination of measures and were then ranked for each of the deprivation indices. SETTING: The 59 electoral wards of the Central Nottinghamshire Health Authority. RESULTS: The Jarman index consistently ranked lower in respect of its correlation with measures of morbidity than did the other deprivation measures. Current unemployment rates correlated well with morbidity measures, in particular with hospital admission rates, with correlations ranging from 0.669 to 0.830 for average and standardised all age admission rates. CONCLUSIONS: The Jarman index seems to be the least appropriate of these indices for health authority use. Unemployment rate merits further consideration as a simple, up to date marker for deprivation and consequent need for health service provision. PMID- 1932936 TI - Risk factors for developing non-insulin dependent diabetes: a 10 year follow up of men in Uppsala. AB - OBJECTIVE: To analyse anthropometric and metabolic characteristics as risk factors for development of non-insulin dependent diabetes mellitus in middle aged normoglycaemic men. DESIGN: Prospective population study based on data collected in a health survey and follow up 10 years later. SETTING: Uppsala, a middle sized city in Sweden. SUBJECTS: 2322 men aged 47-53, of whom 1860 attended the follow up 7-14 years later, at which time they were aged 56-64. MAIN OUTCOME MEASURES: Incidence of non-insulin dependent diabetes. RESULTS: In a multivariate logistic regression analysis, variations of 1 SD from the mean of the group that remained euglycaemic were used to calculate odds ratios and 95% confidence intervals. Blood glucose concentration 60 minutes after the start of an intravenous glucose tolerance test (odds ratio = 5.93, 95% confidence interval 3.05 to 11.5), fasting serum insulin concentration (2.12, 1.54 to 2.93), acute insulin increment at an intravenous glucose tolerance test (1.71, 1.21 to 2.43), body mass index (1.41, 1.01 to 1.97), and systolic blood pressure (1.23, 0.97 to 1.56) were independent predictors of diabetes. In addition, the use of antihypertensive drugs at follow up (selective or unselective beta blocking agents, thiazides, or hydralazine) was an independent risk factor (1.70, 1.11 to 2.60). CONCLUSIONS: Metabolic and anthropometric characteristics associated with or reflecting insulin resistance as well as a poor acute insulin response to glucose challenge were important predictors of future diabetes in middle aged men. Antihypertensive drugs were found to constitute a further, iatrogenic risk factor. PMID- 1932937 TI - Compulsive personality as predictor of response to serotoninergic antidepressants. PMID- 1932938 TI - Doctors and drops. PMID- 1932939 TI - Employment experiences of vocationally trained doctors. AB - OBJECTIVES: To investigate the expectations and employment experiences of male and female doctors who completed vocational training in East Anglia during 1981-7 and to examine the factors which had influenced those who had changed direction early in their careers. DESIGN: Survey conducted by confidential postal questionnaire. SETTING: Britain. SUBJECTS: 281 doctors, 233 (83%) of whom responded. MAIN OUTCOME MEASURES: Ideal choice of work on completion of vocational training; present employment; factors which had restricted present choice of work; factors associated with reported satisfaction with job. RESULTS: 77/83 (93%) men and 130/150 (87%) women had hoped to work in general practice (p = 0.75). A smaller proportion of women (71%; 106) than men (89%; 74) were in general practice posts (p less than 0.01); only 6% (nine) of women were on maternity leave or caring for children without paid employment. More women than men were working in medical jobs other than general practice (18% (27) women v 4% (three) men; p less than 0.01). 44/91 (49%) women with children had achieved their employment goals compared with 47/59 (80%) women without children and 55/71 (78%) men with children. 87% (72/83) of men and 65% (98/150) of women had achieved the status of principal (p less than 0.01). 162/193 (84%) doctors who had worked in general practice reported satisfaction with their jobs. Dissatisfaction was linked with doing a job different from that hoped for and with perceiving that the share of practice income did not accurately reflect their share of the practice workload. CONCLUSIONS: Steps need to be taken to retain women in general practice, including a statutory part time pay allowance and incentives for practices to allow flexible working hours for doctors with young children. PMID- 1932940 TI - The Freeman Hospital. PMID- 1932941 TI - Alcohol as a key area. PMID- 1932942 TI - Role of diabetes. PMID- 1932943 TI - Late complications of undetected urethral stricture after cardiac surgery in a child. PMID- 1932944 TI - Human listeriosis and pate: a possible association. AB - OBJECTIVES: To study trends in human listeriosis and determine possible sources of infection. DESIGN: Descriptive analysis of laboratory reports of human listeriosis together with a survey of subtypes of Listeria monocytogenes isolated from patients and foodstuffs and an interview survey of patients to obtain food histories. SETTING: United Kingdom and Republic of Ireland 1985 to 1990. RESULTS: There was a near doubling in the incidence of human listeriosis in England, Wales, and Northern Ireland between 1985 and mid-1989 followed by a sharp decline. The upsurge in cases was caused largely by two strains of L monocytogenes, which accounted for 30-54% of the annual totals. These strains were less common before 1987 and after July 1989. A survey of pate in England and Wales in July 1989 showed that it frequently contained L monocytogenes. A similar survey in July 1990 showed a reduction in the proportions of samples contaminated. In 1989 pates from a single plant (manufacturer Y) were more likely to be contaminated by L monocytogenes and at higher levels than those from other producers. Most strains of L monocytogenes recovered from manufacturer Y's pate in 1989 were indistinguishable from those responsible for the 1987-9 upsurge in human listeriosis and were uncommon among isolates from pates from other manufacturers and from a wide range of other foodstuffs. Patients infected with the types of L monocytogenes found in pate were significantly more likely to have recently eaten pate than those affected by other strains. The start of the decline in numbers of cases of listeriosis coincided with government health warnings on pate consumption and the suspension of supplies from manufacturer Y. CONCLUSIONS: Contamination of pate was a likely contributory cause of the increase in the incidence of listeriosis between 1987 and 1989. PMID- 1932945 TI - ABC of vascular diseases. Leg ulcers. PMID- 1932946 TI - Notification of hepatitis A. PMID- 1932947 TI - Sexual behavior in Scottish prisons. PMID- 1932948 TI - Zidovudine after exposure to HIV. PMID- 1932949 TI - Skin avulsion during manipulation of fractures. PMID- 1932950 TI - Domiciliary thrombolytic treatment. PMID- 1932951 TI - Homeless people and psychiatric care. PMID- 1932952 TI - Alcohol consumption during pregnancy and infants' development. PMID- 1932953 TI - Is rheumatoid arthritis an infectious disease? PMID- 1932954 TI - Rapid one step urine tests in early pregnancy. PMID- 1932955 TI - Soft tissue injuries to the neck. PMID- 1932956 TI - Management training of senior registrars. PMID- 1932957 TI - Admissions to mental handicap hospitals. PMID- 1932958 TI - Inner city psychiatry. PMID- 1932959 TI - Home from the war. PMID- 1932960 TI - Extracontractual referrals. PMID- 1932961 TI - Malingerers, vagrants, and extracontractual arrangements. PMID- 1932962 TI - Warfarin potentiated by proguanil. PMID- 1932963 TI - Guidelines for radiological investigations. PMID- 1932964 TI - Where is the wisdom...? PMID- 1932965 TI - Exogenous surfactants. PMID- 1932967 TI - Lies, damned lies, and waiting lists. PMID- 1932966 TI - Verocytotoxin producing Escherichia coli. PMID- 1932968 TI - American plan to combat AIDS. PMID- 1932969 TI - A multicentre audit of hospital referral for radiological investigation in England and Wales. Royal College of Radiologists Working Party. AB - OBJECTIVE: A baseline audit of radiology referral practice before the introduction of a strategy for change involving guidelines of good practice, monitoring, and peer review. DESIGN: Prospective data collection over a continuous 12 months period at each centre sometime between January 1987 and December 1989. SETTING: Five district general hospitals and one district health authority. SUBJECTS: 159,421 inpatient discharges, deaths, and day cases and 861,370 outpatient attendances under the care of 722 consultants from 25 clinical specialties. MAIN OUTCOME MEASURES: Monitoring of x ray examination referrals per 100 inpatient discharges, deaths, and day cases and per 100 new outpatient attenders after establishment of a computerised data collection system. RESULTS: Referral rates for all x ray examinations varied between firms in the same specialty or sub-specialty by as much as eightfold for inpatients and 13-fold for outpatients, and for chest x ray examination by as much as ninefold for inpatients and 25-fold for outpatients. There was no consistent relation between high referral and teaching status of the centre or specialty or subspecialty. CONCLUSIONS: The variation that persisted at all levels of disaggregation of the data supports a recent suggestion that at least a fifth of x ray examinations carried out in Britain may be clinically unhelpful. An intervention study that examines the effect of guidelines of good practice and attendant peer review procedures on the baseline referral levels described above is needed to test this hypothesis further. PMID- 1932970 TI - Radiographic examination of the lumbar spine in a community hospital: an audit of current practice. AB - OBJECTIVE: To assess general practitioners' decisions to request lumbar spine radiographs according to the guidelines of the Royal College of Radiologists. DESIGN: Prospective questionnaire survey of outpatients attending for lumbar spine radiography. SETTING: London community hospital. SUBJECTS: 100 consecutive adult outpatients attending for lumbar spine radiography at their general practitioner's request. MAIN OUTCOME MEASURES: Patient's history and clinical signs; radiological diagnosis; change in management of patients with significant radiological abnormality in response to the radiologist's report. RESULTS: 60 patients were aged between 18 and 45, 27 (45%) of whom were women. Five patients were fully examined by their doctor before radiographs were requested, 76 were partially examined, and 19 were not examined. In 37 patients the examinations showed radiologically normal findings; 30 had radiologically significant disc or degenerative disease. Pain score and radiological diagnosis was not correlated (6.43 (range 1-10) for patients with significant disease v 6.14 (range 1-10) for those without, p greater than 0.05). There were no cases of malignancy or infection. One patient with radiologically significant disease was referred to a hospital specialist, and the management of only two such patients was altered by the report. 52 of the examinations should not have been requested if the guidelines had been strictly applied. CONCLUSIONS: There is a need to inform doctors of the efficacy of radiological examinations. An awareness of the college's guidelines among general practitioners should be actively promoted by radiologists. PMID- 1932971 TI - Association between secretor status and respiratory viral illness. AB - OBJECTIVE: To determine whether non-secretion of blood group antigens is associated with respiratory virus diseases. DESIGN: Study of secretor status in patients with respiratory virus diseases determined by an enzyme linked immunosorbent assay (ELISA) developed to identify Lewis (Le) blood group antigen phenotypes (Le(a) non-secretor; Le(b) secretor). SUBJECTS: Patients aged 1 month to 90 years in hospital with respiratory virus diseases (584 nasal specimens). MAIN OUTCOME MEASURES: Criteria for validation of ELISA (congruence between results on ELISA testing of 1155 saliva samples from a previous study and previously established results on haemagglutination inhibition (HAI) testing, proportions of Le(a), Le(b), and Le- phenotypes in 872 samples of nasal washings from a previous study compared with the normal population). Secretor status of patients determined by ELISA and viruses isolated. RESULTS: Agreement between HAI and ELISA for 1155 saliva samples was 97%. Lewis antigens were detected by ELISA in 854 (97.9%) of nasal washings (Le(a) 233 (26.7%), Le(b) 621 (71.2%), and Le- 18 (2.1%)) in proportions predicted for a northern European population. Secretors were significantly overrepresented among patients from whom influenza viruses A and B (55/64, 86%; p less than 0.025), rhinoviruses (63/72, 88%; p less than 0.01), respiratory syncytial virus (97/109, 89%; p less than 0.0005), and echoviruses (44/44, p less than 0.0005) had been isolated compared with the distribution of secretors in the local population. CONCLUSION: Secretion of blood group antigens is associated with respiratory virus diseases. PMID- 1932972 TI - Mode of delivery after one caesarean section: audit of current practice in a health region. AB - OBJECTIVE: To audit the subsequent obstetric management of women who had had one previous baby delivered by caesarean section. DESIGN: Retrospective analysis of a regional obstetric database. SETTING: Data derived from the 17 obstetric units in North West Thames region. SUBJECTS: 1059 women who delivered a singleton fetus of at least 37 weeks' gestation with a cephalic presentation in 1988 who had a history of one previous caesarean section and no other deliveries. MAIN OUTCOME MEASURES: Mode of delivery, postnatal morbidity, and duration of hospital stay. RESULTS: 395 (37%) women were delivered by elective repeat caesarean section and 664 (63%) were allowed a trial of labour. Maternal height and birth weight of the previous infant differed significantly between those who were and those who were not allowed to labour. 471 (71%) of those allowed to labour achieved a vaginal delivery. In individual units there was no significant correlation between the proportion of patients allowed to labour and the rate of the successful trial of labour. There was a trend towards greater success rates in units that allowed a longer duration of labour (p less than 0.05) and units with greater use of oxytocin for augmentation of labour (not significant). Both elective and intrapartum caesarean section was associated with a significantly higher rate of postnatal infection than vaginal delivery (14.7% and 16.0% v 3.4%). CONCLUSIONS: In patients with a history of caesarean section there is no evidence that the likelihood of successful vaginal delivery after trial of labour is modified by the proportion of such patients allowed the option of attempted vaginal delivery. Until selection criteria of adequate prognostic value can be identified a more liberal approach to allowing women a trial of labour seems justified. PMID- 1932973 TI - Differential effects of enalapril and atenolol on proteinuria and renal haemodynamics in non-diabetic renal disease. AB - OBJECTIVE: To compare the antihypertensive, renal haemodynamic and antiproteinuric effect of enalapril and atenolol in patients with proteinuria of non-diabetic origin. DESIGN: Prospective, double blind, randomised 16 week study after a pretreatment period of at least three weeks. SETTING: Outpatient nephrology and hypertension unit. PATIENTS: 27 patients with proteinuria (greater than 300 mg protein/day) of non-diabetic origin, moderately impaired renal function (creatinine clearance 30-90 ml/min), and a pretreatment diastolic blood pressure of greater than 80 mm Hg. INTERVENTIONS: Treatment with enalapril (10 mg/day, adjusted between 5 and 40 mg, if necessary) or atenolol (50 mg/day, adjusted between 25 and 100 mg if necessary) titrated against a target fall in diastolic blood pressure to less than 95 mm Hg or of greater than 10 mm Hg, or both. MAIN OUTCOME MEASURES: Blood pressure, renal haemodynamics, and urinary protein excretion. RESULTS: No differences were detected between the two groups before treatment. The falls in systolic and diastolic blood pressures during treatment were not significantly different between both groups. Proteinuria fell slightly with atenolol but significantly more with enalapril (mean change -0.38 (95% confidence interval -0.78 to 0.03) v -1.2 (-1.70 to -0.69) g/day respectively, p less than 0.02) as did filtration fraction (mean change -1.8 ( 2.9 to -0.7) v -3.8 (-4.9 to -2.8)% respectively. Serum potassium concentration increased with enalapril (mean change 0.63 (SD 0.51) v 0.19 (0.47) mmol/l, p less than 0.05). CONCLUSIONS: Enalapril lowers proteinuria more than atenolol in patients with non-diabetic renal disease despite a similar blood pressure lowering effect of both drugs, and its antiproteinuric effect seems to be associated with the characteristic renal haemodynamic effect of angiotensin converting enzyme inhibitors. PMID- 1932974 TI - Thrombocytosis and ischaemic complications in giant cell arteritis. PMID- 1932975 TI - Secretor status and heterosexual transmission of HIV. PMID- 1932976 TI - General practice as a career. PMID- 1932977 TI - Guidelines for management of patients with psoriasis. Workshop of the Research Unit of the Royal College of Physicians of London; Department of Dermatology, University of Glasgow; British Association of Dermatologists. PMID- 1932978 TI - Housing. PMID- 1932979 TI - Commitment vital for new deal. PMID- 1932980 TI - East Birmingham: running faster on the spot. PMID- 1932981 TI - ABC of vascular diseases. The young patient with claudication. PMID- 1932982 TI - Omeprazole. PMID- 1932983 TI - Confidentiality taken to the extreme. PMID- 1932984 TI - Papaveretum in women of childbearing potential. PMID- 1932985 TI - Computers in audit: servants or sirens? PMID- 1932986 TI - Not research and development. PMID- 1932987 TI - Post-traumatic stress disorders. PMID- 1932988 TI - Gas gangrene. PMID- 1932989 TI - Advances in cell kinetics. PMID- 1932990 TI - Pain after subcutaneous injection of erythropoietin. PMID- 1932991 TI - Treating bony metastases. PMID- 1932992 TI - Deprivation indices. PMID- 1932993 TI - Mandatory assessment of patients aged over 75. PMID- 1932994 TI - Fellowship of the RCGP by assessment. PMID- 1932995 TI - Nursing: an intellectual activity. PMID- 1932996 TI - Payment for drugs. PMID- 1932997 TI - Society, health, and the NHS. PMID- 1932998 TI - Doctors and the Children Act. PMID- 1932999 TI - Aging and rationing. PMID- 1933000 TI - Anaesthetics and elderly patients. PMID- 1933001 TI - Corticosteroids and tuberculosis. PMID- 1933002 TI - Monkey business over AIDS vaccine. PMID- 1933003 TI - Mortality from causes amenable and non-amenable to medical care: the experience of eastern Europe. AB - OBJECTIVE: To investigate comparative national trends in mortality from conditions amenable to timely, appropriate medical care and from those considered not to be amenable to such care. DESIGN: Analysis of trends in direct age standardised mortality from the 1950s to 1987. SETTING: Four eastern European nations (Hungary, Czechoslovakia, Poland, the German Democratic Republic) and two western European (the Federal Republic of Germany and England and Wales) and two North American nations (United States and Canada). SUBJECTS: The total populations of the relevant countries during the period examined. MAIN OUTCOME MEASURES: Proportional changes over time in age standardised mortality. Mortality from amenable and non-amenable causes was restricted to the age group 0-64. RESULTS: A divergence in the trends for all cause mortality between eastern Europe and the western nations occurred in about 1970, when the rates in western countries steadily declined but those in eastern Europe remained fairly static. In the age group 0-64 mortality from causes considered amenable to medical care fell less quickly in eastern Europe than in the West, particularly after 1970. In the same age group, mortality from non-amenable causes rose in eastern European countries from the late 1960s compared with substantial declines in such mortality in the West. CONCLUSIONS: Non-amenable causes of death seem to be the principal, but not exclusive, reason for lack of improvement in trends in all cause mortality in eastern Europe from 1970. The agenda for action in eastern Europe should give priority to a healthier lifestyle and improvement of the environment though not neglect enhancements in the quality and efficiency of direct health services. PMID- 1933004 TI - Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. AB - OBJECTIVES: (a) To determine the excess mortality from all causes and from coronary heart disease in patients with familial hypercholesterolaemia; (b) to examine how useful various criteria for selective measurement of cholesterol concentration in cardiovascular screening programmes are in identifying these patients. DESIGN: Prospective cohort study. SETTING: Eleven hospital outpatient lipid clinics in the United Kingdom. PATIENTS: 282 men and 244 women aged 20-74 with heterozygous familial hypercholesterolaemia. MAIN OUTCOME MEASURE: Standardised mortality ratio, all adults in England and Wales being taken as standard (standardised mortality ratio = 100 for standard population). RESULTS: The cohort was followed up for 2234 person years during 1980-9. Fifteen of the 24 deaths were due to coronary heart disease, giving a standardised mortality ratio of 386 (95% confidence interval 210 to 639). The excess mortality from this cause was highest at age 20-39 (standardised mortality ratio 9686; 3670 to 21,800) and decreased significantly with age. The standardised mortality ratio for all causes was 183 (117 to 273) and also was highest at age 20-39 (standardised mortality ratio 902; 329 to 1950). There was no significant difference between men and women. Criteria for measurement of cholesterol concentration in cardiovascular screening programmes (family history, presence of myocardial infarction, angina, stroke, corneal arcus, xanthelasma, obesity, hypertension, diabetes, or any of these) were present in 78% of patients. CONCLUSIONS: Familial hypercholesterolaemia is associated with a substantial excess mortality from coronary heart disease in young adults but may not be associated with a substantial excess mortality in older patients. Criteria for selective measurement of cholesterol concentration in cardiovascular screening programmes identify about three quarters of patients with the clinically overt condition. PMID- 1933005 TI - Is necropsy a valid monitor of clinical diagnosis performance? AB - OBJECTIVE: To improve the validity of comparisons between clinical and postmortem diagnoses when postmortem diagnosis is used to monitor clinical diagnosis performance. DESIGN: Analysis of elementary examples. MAIN OUTCOME MEASURES: Sensitivity and specificity of clinical and postmortem diagnoses and confirmation and agreement rates. Sensitivity and specificity permit valid comparisons of clinical and postmortem diagnoses among different procedures, sites, or times whereas agreement and confirmation rates may be misleading. Estimates of sensitivity and specificity, however, can be severely distorted by factors such as non-random selection of cases for necropsy or by unrecognised errors in postmortem diagnosis. Such distortion may be minimised by (a) estimating the likely magnitude of errors in postmortem diagnosis, (b) specifying standard conditions for performing necropsies, and (c) ensuring an unbiased sample of moderate size rather than a large biased sample. CONCLUSION: Sensitivity and specificity should be used as measures of agreement between clinical and postmortem diagnoses. IMPLICATION: Monitoring of clinical diagnosis performance by necropsy surveys requires ensuring accuracy of pathological examinations and validity of study design and analysis. PMID- 1933006 TI - Quality and health care in Sweden. PMID- 1933007 TI - Budget holding: the first 150 days in Calverton. PMID- 1933008 TI - Work related disease and injuries. PMID- 1933009 TI - Exercise. PMID- 1933010 TI - ABC of vascular diseases. Raynaud's syndrome and similar conditions. PMID- 1933011 TI - Manpower and hours of work agreements are complementary. PMID- 1933012 TI - Preventing osteoporosis. PMID- 1933013 TI - Accidental ingestion of methadone. PMID- 1933014 TI - Orthopaedic surgeons and thromboprophylaxis. PMID- 1933015 TI - Blood pressure and myocardial infarction. PMID- 1933016 TI - Pneumothorax after fine needle aspiration of the breast. PMID- 1933018 TI - Pyoderma gangrenosum. PMID- 1933017 TI - Adenoma screening and colorectal cancer. PMID- 1933019 TI - Taxation of alcoholic beverages. PMID- 1933020 TI - Health of the nation. PMID- 1933021 TI - Consultants in communicable disease control. PMID- 1933022 TI - The spectrin super-family. AB - The review is focused on recent data on the primary sequences of erythroid and non-erythroid spectrins. As in other fields, the techniques of molecular genetics have allowed great advances in our knowledge of the structure and the genetic story of these molecules. Comparison of alpha-chains sequences of the non erythroid (fodrin) and erythroid spectrin demonstrated that the fodrin alpha genes are strictly conserved across species, while the mammalian spectrin genes have diverged rapidly. Spectrin and fodrin alpha-chains are largely composed of homologous 106-amino-acid repeat units. Spectrin alpha-chain is lacking a 37 amino-acid sequence which bears the calmodulin-binding site of the fodrin alpha chain. The highest degree of homology between the spectrin alpha-chain and the fodrin alpha-chain lies in a central atypical segment unrelated to the canonical repeat sequence. This region is closely related to the N-terminal segment of several src-tyrosine kinases and to a domain of phospholipase C. Like the spectrin alpha-chain, the major central part of the spectrin beta-chain is made up of repeat units of 106 amino-acids. The N-terminal domain of the beta-chain, and especially the actin binding site, is the region of greatest homology among members of the spectrin super-family, including Drosophila spectrin beta-chain, dystrophin and alpha-actinin. The C-terminal extremity of the erythroid beta chain is also of great interest, since tissue-specific differential processing of 3'beta-spectrin gene pre-mRNA generates a beta spectrin-isoform with a unique C terminus in human skeletal muscle. PMID- 1933023 TI - Establishment of endometrial glandular epithelial cell subculture in a serum free, hormonally defined medium, on a basement membrane matrix. AB - Epithelial glands were isolated from guinea-pig endometrium. In order to reduce the requirement for a serum supplement and the contamination by non epithelial cells in primary culture, various coatings of the culture dishes were tested using serum-free Ham's F12 containing defined chemicals including 17 beta estradiol. While epithelial glands seeded on culture dishes coated with Matrigel, a basement membrane matrix-failed to spread, they formed on poly-D-lysine plus serum-coated dishes, a subconfluent monolayer (5-7 days) enriched in cytokeratin immunostained cells (78%). Cells from subconfluent primary cultures, obtained on poly-D-lysine plus serum-coated dishes in serum-free hormonally defined medium, were passaged on Matrigel-coated dishes in serum-free hormonally defined medium. These subcultures contained, at confluence (4-5 days), a high percentage (greater than 95%) of cytokeratin-immunostained cells. These monolayers consisted of well differentiated cells which exhibited ultrastructural features characteristic of endometrial epithelial cells. Moreover, these confluent cells contained 50% immunostained nuclei for progesterone receptors. Progesterone receptor amounts decreased in confluent subcultures treated with progesterone and became undetectable after long-term treatment, suggesting responsiveness of these cells to progesterone. This culture system provides a well-defined model for the study of protein synthesis and secretion by endometrial glandular epithelial cells under hormonal control. PMID- 1933025 TI - Membrane fluidity aspects in endocytosis; a study with the fluorescent probe trimethylamino-diphenylhexatriene in L929 cells. AB - The fluorescent hydrophobic plasma membrane probe, trimethylamino diphenylhexatriene (TMA-DPH) was previously shown to follow the plasma membrane throughout its internalization and recycling process and thus to behave as a marker for endo- and exocytosis in living cell systems. In this paper, we made use of these properties to investigate membrane fluidity effects associated with endocytosis in L929 cells. For that purpose we performed TMA-DPH fluorescence anisotrophy measurements which showed that endocytosis starts from particularly rigid regions of the plasma membrane (probably coated pits). The fluorescence anisotropy then continuously decreases to a lower limit corresponding to the membrane fluidity of the probe in the lysosomial membrane. Strikingly, the value of this limit is identical to the average anisotropy value in the peripheral membrane, which suggests that lysosomes and plasma membrane may have a similar phospholipidic composition and a possible common origin. PMID- 1933024 TI - The synthesis and accumulation of membrane protein 4.1 in Friend erythroleukemia cells. AB - The effect of extensive differentiation on the synthesis and accumulation of protein 4.1 were studied on Friend erythroleukemia cells grown in suspension and on fibronectin coated dishes. Whole membranes of Friend erythroleukemia cells (FELC) contained a protein 4.1a and 4.1b doublet of Mr 76 and 74 kDa and two minor bands of Mr 105 and 43 kDa that cross-reacted with anti-human protein 4.1 IgG. These proteins were present even in uninduced cells. The synthesis of protein 4.1 was maximal after 4 days of induction in both suspension culture and in fibronectin-coated dishes whereas the protein 4.1 continued to accumulate until the seventh day. More protein 4.1 accumulated in cells grown on fibronectin coated dishes, at each stage of differentiation, than in cells grown in suspension. The protein 4.1a/4.1b ratio changed during differentiation. The amounts of protein 4.1b increased progressively after induction until the protein 4.1a/4.1b ratio was similar to that of mouse mature erythrocyte. The protein 4.1a/4.1b ratio appears to be an internal marker of erythroid differentiation. PMID- 1933026 TI - Three-dimensional analysis demonstrates the presence of exocrine cytoplasmic vela between endocrine cells and basal lamina in the stomach of mammals. AB - Three-dimensional analysis demonstrated the presence of cytoplasmic vela extending from exocrine cells into the space between endocrine cells and basal lamina in the gastrointestinal epithelium of the rabbit; these structures were also observed in various other mammals. The following techniques were used to determine the morphologic characteristics of these vela and to study their significance: preparation of semiserial thin sections, three-dimensional reconstruction in plexiglass and lanthanum staining of pericellular spaces. It was found that these fine vela, devoid of major differentiated cell-constituents, sometimes form a pseudocircular crown at the base of endocrine cells. If the zone of basal apposition of the plasma membrane is referred to as ZBA and the zones of lateral apposition as ZLA, the presence of this velum makes it possible to distinguish a zone of immediate apposition without interposition (ZIA) and a mediate zone of apposition with interposition (ZMA) within the ZBA. Exocrine cell processes can also penetrate within endocrine cells in invaginations, and the depth of these invaginations can be demonstrated by lanthanum staining. Adjacent to the membrane zones defined above, other cytoplasmic microdomains-M(ZLA) and M(ZBA), as well as M(ZIA) and M(ZMA) of different morphofunctional significance may also be envisaged. PMID- 1933027 TI - The Sertoli-spermatid processes in the mouse: new cellular structure. AB - In addition to the known Sertoli-cell processes, processes of the mouse spermatid's cytoplasm are found to invaginate neighbouring spermatids. Surrounded by the adjacent Sertoli process, the spermatid processes form a "spermatid Sertoli cell process". They are observed between spermatids at the same step or at different steps of their development and degenerate mostly at step 13 to 15 of spermiogenesis. Whether these structures are related to either spermatid exchanges or connections or participate to cytoplasm elimination is discussed. PMID- 1933029 TI - Effect of dermal tumours on temperature distribution in skin with variable blood flow. AB - Several investigations have been made for the heat flow problems in skin and subdermal tissues under normal physiological and atmospheric conditions. This paper considers the existence of a malignant tumour in the underlying tissues of epidermis of a human body. The surrounding tissues are assumed to have normal physiological functions, namely self-controlled metabolic activity, variable blood flow and perspiration. For the malignant portion the metabolic activity is taken to be continuous and uncontrolled. The effect of this factor is studied on the temperature profiles of the skin. PMID- 1933028 TI - The thalamocortical contribution to epilepsy. AB - The experimental literature has dealt intensively with the cortical contribution to epilepsy. Possibly because of the direction of technological advance, much less attention has been paid to the role of other structures. A model which emphasizes the role of some of those non-cortical structures, specifically that of thalamocortical modulation of cortical excitability, is developed. Some aspects of the petit mal seizure, a seizure type considered by some investigators to involve thalamocortical mechanisms, are predicted by the model. Although the thalamocortical mechanisms under study are not the only mechanisms underlying seizures, a full understanding of the phenomenology of epilepsy needs to take into account the role of subcortical modification of cortical activities in addition to other mechanisms. Gloor has described two types of epileptogenesis: type I characteristic of non-convulsive seizures and type II characteristics of convulsions. There is disagreement as to whether or not the two mechanisms represent qualitatively different phenomena. Utilizing the thalamocortical model, it can be shown that the two types of epileptogenesis are qualitatively different. Furthermore, the thalamocortical model leads to a possible explanation of clinically different profiles of antiepileptic efficacy of medications. PMID- 1933030 TI - Statistical evaluation of dendritic growth models. AB - A mathematical model (Kliemann, W. 1987. Bull. math. Biol. 49, 135-152.) that predicts the quantitative branching pattern of dendritic tree was evaluated using the apical and basal dendrites of rat hippocampal neurons. The Wald statistic for chi 2-test was developed for the branching pattern of dendritic trees and for the distribution of the maximal order of the tree. Using this statistic, we obtained a reasonable, but not excellent, fit of the mathematical model for the dendritic data. The model's predictability of branching pattern was greatly enhanced by replacing one of the assumptions used for the original method "splitting of branches for all dendritic orders is stochastically independent", with a new assumption "branches are more likely to split in areas where there is already a high density of branches". The modified model delivered an excellent fit for basal dendrites and for the apical dendrites of hippocampal neurons from young rats (30-34 days postpartum). This indicates that for these cells the development of dendritic patterns is the result of a purely random and a systematic component, where the latter one depends on the density of dendritic branches in the brain area considered. For apical dendrites there is a trend towards decreasing pattern predictability with increasing age. This appears to reflect the late arrival of afferents and subsequent synaptogenesis proximal on the apical dendritic tree of hippocampal neurons. PMID- 1933031 TI - Computer simulations of cell-target encounter including biased cell motion toward targets: single and multiple cell-target simulations in two dimensions. AB - In order for immune cells to carry out many of their functions, including clearance of infectious agents from tissue, they must first encounter their targets in the tissue. This encounter process is often the rate-limiting step in the overall function. Most immune cells exhibit chemotactic ability, and previous continuum models for encounter rates and dynamics have shown that chemotaxis can be a great advantage to cells by greatly increasing encounter rates relative to those for randomly moving cells. This paper describes computer simulations of discrete cell-target encounter events in two dimensions, for the two cases considered by the continuum models: where only a single cell and a single target are present, and where many cells and targets are present. The results of these simulations verify our previous model predictions that a small amount of chemotactic bias dramatically decreases the encounter time, while further increases in the amount of bias have a much smaller effect. Chemotactic ability is shown to be an important determinant of the kinetics of target clearance, and its effects depend on the initial cell-target ratio and the initial distributions of cells and targets. To the best of our knowledge, this work provides the first computer simulations of particle-target encounter in which there is biased motion of particles toward their targets, and is therefore of general interest beyond specific application to immune cell function. PMID- 1933032 TI - Autocrine and paracrine growth factors in tumor growth: a mathematical model. AB - A mathematical model of tumor growth including autocrine and paracrine control has been developed. The model starts with the logistic equation of Verhulst: dV/dt = rV (1-V/K). Autocrine controls are described as modifiers of the Malthusian growth rate (r), while paracrine controls modify the carrying capacity (K) of the system. The control mechanisms are expressed in terms of "candidate" functions, which are based upon the dynamic distribution of TGF-alpha TGF-beta in the local tumor environment. Three paradigms of tissue growth have been modeled: normal tissue wound repair, unrestricted, unperturbed tumor growth, and tumor growth in a (radiation) damaged environment (the Tumor Bed Effect, TBE). These scenarios were used to test the dynamics of the system against known phenomena. Computer simulations are presented for each case. The mode is being extended to include the description of heterogeneous tumors, within which subpopulations can express differential degrees of growth activity. Heterogeneous tumor models, with and without emergent subpopulations, and models of terminal differentiation are also discussed. PMID- 1933034 TI - Consensus weak hierarchies. AB - An axiomatic characterization is presented for consensus functions defined on weak hierarchies. These functions are generalizations of the majority rule consensus. PMID- 1933033 TI - The estimation of the Kolmogorov entropy from a time series and its limitations when performed on EEG. AB - A method to estimate a lower bound of the Kolmogorov entropy-the so called K2 entropy-from a time series is presented which avoids use of the generalized correlation integral. The influence of the norm is studied. The method is demonstrated on some standard examples. The entropy of the attractor apparent in the EEG of the foetal sheep is estimated and the results are compared with results obtained from synthesized data featuring some basic properties of EEG. This gives an insight into the limitations of the procedure. PMID- 1933035 TI - Analysis of oscillations in yeast continuous cultures by a new simplified model. AB - The autonomous oscillations in yeast continuous cultures are investigated analytically and related to the behaviour of the single cell by means of a suitable modified version of Monod's classical chemostat model. Two main cell phases or states are considered to account for the experimentally observed changes occurring in the cell growth course: the budded phase and the unbudded one. Thus, a sort of two compartment structure is given to the total biomass. The model so far obtained allows one to analyse the local properties of the predicted steady states under various assumptions, both on the yield coefficients and the specific growth rates. Necessary conditions for the local instability are derived and the existence of stable limit cycles is shown by computer simulation. With respect to the qualitative changes in the metabolic parameters, this analysis agrees with the results obtained by simulation of complex structured and segregated models. However, the oscillation period is too long compared with the experimental one and this fact may be mainly due to the strong simplifying assumptions on the dynamic evolution of the transfer rates between the two compartments. The model's usefulness seems until now restricted to the identification of the relationships between the cell cycle regulation and the oscillation triggering. PMID- 1933036 TI - Bifurcating spatially heterogeneous solutions in a chemotaxis model for biological pattern generation. AB - We consider a simple cell-chemotaxis model for spatial pattern formation on two dimensional domains proposed by Oster and Murray (1989, J. exp. Zool. 251, 186 202). We determine finite-amplitude, steady-state, spatially heterogeneous solutions and study the effect of domain growth on the resulting patterns. We also investigate in-depth bifurcating solutions as the chemotactic parameter varies. This numerical study shows that this deceptively simple-chemotaxis model can produce a surprisingly rich spectrum of complex spatial patterns. PMID- 1933037 TI - Analysis of chemotactic bacterial distributions in population migration assays using a mathematical model applicable to steep or shallow attractant gradients. AB - The mathematical model developed by Rivero et al. (1989, Chem. Engng Sci. 44, 2881-2897) is applied to literature data measuring chemotactic bacterial population distributions in response to steep as well as shallow attractant gradients. This model is based on a fundamental picture of the sensing and response mechanisms of individual bacterial cells, and thus related individual cell properties such as swimming speed and tumbling frequency to population parameters such as the random motility coefficient and the chemotactic sensitivity coefficient. Numerical solution of the model equations generates predicted bacterial density and attractant concentration profiles for any given experimental assay. We have previously validated the mathematical model from experimental work involving a step change in the attractant gradient (Ford et al., 1991 Biotechnol. Bioengng, 37, 647-660; Ford and Lauffenburger, 1991, Biotechnol. Bioengng, 37, 661-672). Within the context of this experimental assay, effects of attractant diffusion and consumption, random motility, and chemotactic sensitivity on the shape of the profiles are explored to enhance our understanding of this complex phenomenon. We have applied this model to various other types of gradients with successful interpretation of data reported by Dalquist et al. (1972, Nature New Biol. 236, 120-123) for Salmonella typhimurium validating the mathematical model and supporting the involvement of high and low affinity receptors for serine chemotaxis by these cells. PMID- 1933038 TI - The embedding problem for predistance matrices. AB - A fundamental problem in molecular biology is the determination of the conformation of macromolecules from NMR data. Several successful distance geometry programs have been developed for this purpose, for example DISGEO. A particularly difficult facet of these programs is the embedding problem, that is the problem of determining those conformations whose distances between atoms are nearest those measured by the NMR techniques. The embedding problem is the distance geometry equivalent of the multiple minima problem, which arises in energy minimization approaches to conformation determination. We show that the distance geometry approach has some nice geometry not associated with other methods that allows one to prove detailed results with regard to the location of local minima. We exploit this geometry to develop some algorithms which are faster and find more minima than the algorithms presently used. PMID- 1933039 TI - Planning for community care: the Community Placement Questionnaire. AB - The article reviews methodological issues relating to planning surveys of long stay populations and describes the development of an assessment instrument, the Community Placement Questionnaire, designed to aid planning for long-stay patients resident in hospitals scheduled for rundown or closure. Reliability and validity data are presented and the advantages and limitations of the instrument are discussed. PMID- 1933040 TI - Reality monitoring and psychotic hallucinations. AB - Hallucinating psychiatric patients, patients with delusions but without a history of hallucinations and normal controls were compared on a reality-monitoring task in which they were first required to generate answers to easy or difficult clues and to listen to low-probability or high-probability paired associates. After an interval of one week, the subjects were presented with a list in which their answers to the clues were mixed with the associates and with words not previously presented, and they were required to identify the source of each item (self generated, presented by the experimenter or new). The psychiatric patients were generally less accurate in identifying the source of the items in comparison with the normal controls. However, hallucinators more often misattributed high cognitive effort self-generated items (answers to difficult clues) to the experimenter than either the psychiatric or the normal controls. The results are interpreted as consistent with the hypothesis that hallucinations are self generated events misattributed to an external source. PMID- 1933041 TI - The Short NART: cross-validation, relationship to IQ and some practical considerations. AB - Beardsall & Brayne (1990) have presented a method whereby the full-length National Adult Reading Test (NART) scores of subjects who are of below average reading ability can be predicted from performance on the first half of the test (termed the Short NART). The accuracy with which the Short NART predicted full length NART scores was examined in a large cross-validation sample (N = 674). A subgroup of this sample (N = 142) was administered the WAIS. The results indicated that the Short NART was only moderately successful in predicting full length NART scores. However, comparison of the accuracy with which the full length NART and Short NART predicted WAIS IQs, revealed that the superiority of the former was very minimal. It is concluded that, despite some reservations regarding the Short NART's practical utility, it can be used with reasonable confidence in clinical practice to estimate premorbid IQ. PMID- 1933042 TI - Expressed emotion and panic-fear in the prediction of diet treatment compliance. AB - The 'expressed emotion' (EE) of the key relatives of 30 severely obese patients was assessed on intake to a calorie-restricted diet programme. At the same time the patients and 30 matched controls were administered the MMPI 'panic-fear' scale. After five months on the diet the weight of the patients was measured, and weight loss or gain in the five-month period was used as an indicator of compliance or non-compliance with the treatment. The results indicated that the obese patients showed more anxiety (measured by the panic-fear scale) than did the control subjects. Compliant patients had lower panic-fear scores than did non compliant patients, and patients living with a high EE relative were much less likely to comply with treatment than were those living with a low EE relative. Patients with a high EE relative were more likely to have a high panic-fear score. The results suggest that dietary treatments for obesity need to be accompanied by both individual and family behavioural interventions. PMID- 1933043 TI - The stability of attributional style and its relation to psychological distress. AB - A group of yound adults completed the Attributional Style Questionnaire and measures of depressive affect and hopelessness on two occasions separated by a time interval of three years. Attributional style was demonstrated to be relatively stable over this time period, and was correlated with the measures of psychological well-being. Specifically, those who scored highest on depressive affect and hopelessness attributed good outcomes more externally and less stably, and attributed bad outcomes to relatively more stable and global causes. In contrast to the hopelessness model of depression, however, multiple regression analyses showed that depressive attributions were not antecedent to increased psychological distress; nor were they a consequence. Furthermore, negative life events did not contribute to the prediction. It was concluded that the data are most consonant with Brewin's (1985) symptom model, in which depressive attributions are a concomitant or symptom of depression but have no causal impact on the onset or course of the disorder. PMID- 1933044 TI - Profile analysis of the Wechsler intelligence scales: a new index of subtest scatter. AB - A statistical method of profile analysis originally suggested by Huba (1985, 1986), the Mahalanobis distance, D2, is described and discussed with reference to its use with the Wechsler scales. Examples are given to illustrate the properties of D2 and two BASIC computer programs are presented that will calculate D2; one for the WAIS-R and the other which can be readily adapted to the test selection of the user's choice. It is argued that D2 is a useful addition to existing methods of statistical analysis of the Wechsler scales. PMID- 1933045 TI - Dieting concerns have a functional effect on the behaviour of nine-year-old girls. AB - The eating patterns of restrained and unrestrained nine-year-old girls were compared. Prospective seven-day food diary records showed the restrained girls to eat significantly less energy and dietary fibre than the unrestrained. Their ratings of hunger were also significantly higher. Most nutritional indicators, however, showed their diet to be of adequate quality. The translation of dieting concerns into dieting behaviour by nine-year-olds may increase their susceptibility to future clinical eating problems. PMID- 1933046 TI - Return to work during the year following first myocardial infarction. AB - This study considers the importance of demographic and psychosocial variables in return to work following a first myocardial infarction. Those patients who returned to work within two months of their infarct, compared with those who had not returned, tended to be younger and of higher socio-economic status. They were also more likely to have an internal locus of control and to have attributed their MI to occupational stressors. Conversely, patients who had not resumed employment one year following their infarction, in comparison with those who had, were likely to be of lower socio-economic status and to have been more depressed immediately following their heart attack. PMID- 1933047 TI - The focus of pessimism in performance assessments by the depressed. AB - The study concerns the microstructure of pessimistic judgements concerning personal performance in the depressed. The cognitive bias hypothesis was only supported for global estimates of performance and not for trial-by-trial decisions. This weakens the view that there is a fixed cognitive pessimistic bias and leaves open the possibility either that differences relate to the assessment of frequency or to protective strategies operated by the depressed. PMID- 1933048 TI - Effects of induced elated and depressed mood on self-focused attention. AB - Recent accounts of depression propose a central role for increased self-focus in the onset and maintenance of depression. The present study investigated whether there might also be a converse effect of depressed mood increasing self-focus. A state measure of self-focused attention was administered to normal subjects before and after induction of depressed or happy mood. Compared to happy subjects, depressed subjects showed more negative and less positive self-focus. Positive and negative external focus were unaffected by mood. A reciprocally reinforcing relationship between depressed mood and negative self-focus may be important in onset and maintenance of depression. PMID- 1933049 TI - Pressor effects of caffeine and cigarette smoking. AB - Pressor effects of caffeine and cigarette smoking were examined in 15 normotensive young men and women. A cross-over design was used in which all subjects participated in four separate conditions: placebo alone, caffeine alone, placebo plus smoking, and caffeine plus smoking. Caffeine and smoking produced independent increases in systolic and diastolic blood pressure, and these effects were additive in the caffeine-plus-smoking condition. Heart rate was significantly increased by smoking but was essentially unaffected by caffeine. PMID- 1933051 TI - Cytotoxic and proliferative functions of T lymphocyte clones derived very shortly after allogeneic bone marrow transplantation. AB - In a search for mechanisms of potential graft-versus-leukaemia (GVL) activity after allogeneic bone marrow transplantation (BMT), peripheral lymphocytes from five patients (four chronic myeloid leukaemia, one acute lymphoblastic leukaemia) 24-39 days post-transplant were precultured with pretransplant host leukaemia cells and then cloned by limiting dilution with interleukin-2 (IL-2). Clones obtained were exclusively CD3+ CD56-, carried the alpha/beta form of the T cell receptor for antigen, and were mostly (88% of 138) CD4+. None of 143 clones, including CD8+ clones, convincingly lysed host pretransplant cells, although 35 (24.5%) manifested lytic potential in lectin-mediated cytotoxicity assays. Measuring the proliferative responses of 118 of these clones in the presence of exogenous IL-2 revealed that a small number of clones reacted more strongly to host leukaemia than to unrelated leukaemias or B lymphoblastoid cell lines. In the two cases tested, the donor's untransplanted lymphocytes cloned under the same conditions as post-transplant cells did not generate any clones reacting preferentially with host leukaemia cells. These results may suggest that some T cells appearing shortly after allogeneic BMT could potentially mediate anti leukaemia activity not associated with cytolysis of target cells. PMID- 1933050 TI - Prevention of acute GVHD by in vivo use of anti-interleukin-2 receptor monoclonal antibody (33B3.1): a feasibility trial in 15 patients. AB - Results of allogeneic bone marrow transplantation (BMT) are still impaired due mainly to acute graft-versus-host disease (GVHD). Successful T cell depletion may abolish GVHD but causes increased rates of rejection and relapse. In vivo blocking of the CD25 receptor on T cells induces efficient and selective immunosuppression. We present results of a pilot trial studying the use of a CD25 MoAb (33B3.1) to prevent acute GVHD after allogeneic BMT. Fifteen patients were included in the study; 14 had a fully HLA matched sibling donor. In association with short methotrexate and cyclosporin A post-graft immunosuppression, the patients received 10 mg of 33B3.1 monoclonal antibody daily according to three successive schedules to study toxicity on marrow graft. No major adverse clinical experiences occurred. Engraftment was not delayed; after 4 months, full chimerism was documented in 14/15 studied patients. No human anti-rat antibody was detected during treatment period. No GVHD occurred during the period of antibody administration. Two patients relapsed; seven are alive and well with a median follow-up of 650 days. This study justifies a prospective controlled study to determine the real impact of 33B3.1 on GVHD prophylaxis. PMID- 1933052 TI - Is treatment intensification by adding etoposide and carboplatin to fractionated total body irradiation and melphalan acceptable in children with solid tumors with respect to toxicity? AB - Conventional chemotherapy results in high mortality rates in patients with solid tumors involving the bones or the bone marrow. High dose melphalan (MEL) with or without total body irradiation followed by bone marrow transplantation (BMT) has prolonged survival, but curative potential has remained disappointing. In order to improve survival 20 children with generalized or relapsed solid tumors (neuroblastoma, peripheral neuroectodermal tumor, Ewing's sarcoma, rhabdomyosarcoma) underwent autologous (n = 16) or allogeneic (n = 4) BMT. The myeloablative regimen consisted of 12 Gy fractionated total body irradiation (FTBI) and high dose MEL. In 12 of these patients this regimen was intensified by giving 60 mg/kg etoposide (1800 mg/m2 VP), and 1.5 g/m2 carboplatin (CBDCA) was added in seven of these 12 patients. The intensification of FTBI and MEL by adding VP and CBDCA was followed by acceptable toxicity. Acute liver toxicity in 15/20 patients (75%) and acute renal toxicity in 17/20 patients (85%) did not exceed WHO grade 1. The use of the conditioning regimen FTBI-MEL-VP-CBDCA during first chemotherapy response is a promising approach in treatment of children suffering from generalized solid tumors. PMID- 1933053 TI - Maintenance treatment with recombinant alpha interferon after autologous bone marrow transplantation for aggressive myeloma in first remission after conventional induction chemotherapy. AB - Twenty patients (median age 57 years) with high tumor mass myeloma in first remission after conventional chemotherapy received a two-phase treatment: autologous bone marrow transplantation (ABMT) using a preparative regimen of high dose melphalan plus total body irradiation followed by maintenance treatment with recombinant alpha interferon. Before ABMT all patients were in partial remission, while after ABMT 10 (50%) achieved complete remission, and 10 remained in partial remission (with a 90% decrease in measurable paraprotein in 7/10). With a median follow-up of 19.8 months (12.2-33.5) after diagnosis and 13 months (4-25) after ABMT, the Kaplan-Meier 2-year post-ABMT probability of progression-free survival was 85% (95% CI = 58.7-95.8%). None of the 10 patients in complete remission has relapsed. No toxic death occurred. Alpha interferon was introduced early after ABMT (2.7 months) and was well tolerated. This strategy may represent an advance in the management of aggressive myeloma. PMID- 1933054 TI - Renal function after autologous bone marrow transplantation. AB - Seventy-two out of 102 consecutive patients autografted for various hematologic and lymphoid malignancies had a relapse-free survival of greater than 6 months after autologous bone marrow transplantation (ABMT) and were evaluated for long term effect of the treatment on the renal function. The myeloablative therapy included total body irradiation (TBI) in a single fraction of 7.5 Gy in 41/72 patients. Mean glomerular filtration rate (GFR) showed a significant decrease (p less than 0.01) and serum creatinine and serum urea an increase (p less than 0.05) 6 months after ABMT. Twelve of 72 patients (17%) developed renal dysfunction defined as greater than 25% decrease in GFR, in most cases accompanied by hematuria and proteinuria. Onset was 3-6 months after ABMT. Some patients have later improved considerably, but others continue to deteriorate in renal function. The single most important risk factor for renal dysfunction after ABMT was irradiation. Renal damage was most frequent in lymphoma patients conditioned with BEAC (carmustine [BCNU], etoposide, cytarabine, cyclophosphamide) followed by irradiation, suggesting that this drug combination might have potentiated the toxicity of irradiation. Nephrotoxic antibiotics probably contributed to renal damage in individual cases. Young age did not appear to be a risk factor. Our data indicate that combined treatment with BEAC and TBI should be used with caution and that renal function should be monitored in all patients after bone marrow transplantation to detect any new toxicity patterns of the various conditioning regimens currently used. PMID- 1933056 TI - Successful treatment of disseminated Fusarium infection after autologous bone marrow transplantation for acute myeloid leukemia. AB - Disseminated Fusarium is a rare but life-threatening infection of severely immunocompromised patients. A fatal outcome has been described in all reported cases of Fusarium infection occurring after bone marrow transplantation. We describe a patient who developed disseminated Fusarium infection with a secondary fungal endophthalmitis after an autologous bone marrow transplant for acute myeloid leukemia. This infection was successfully eradicated after neutrophil recovery by prolonged systemic administration of amphotericin B as well as aggressive local therapy including enucleation of the affected eye. The patient remains free of both leukemia and fungal disease more than 4 years after transplant. PMID- 1933055 TI - Autologous bone marrow transplantation for progressive non-Hodgkin's lymphoma: clinical impact of immunophenotype and in vitro purging. AB - From 1983 to 1989 we performed a prospective trial of 70 consecutive, in vitro purged autologous bone marrow transplants (BMT) for patients with progressive non Hodgkin's lymphoma. Forty-nine patients had responsive disease at the time of transplantation while 21 others had refractory high risk lymphoma. Forty-two patients with B-lineage lymphoma received autologous marrow purged in vitro with monoclonal antibody (anti CD9, CD10, CD24) plus complement, 12 with T-lineage lymphoma received monoclonal antibody immunotoxins (anti CD5, CD7-ricin conjugates) along with 4-hydroperoxycyclophosphamide purging and 16 received unpurged marrow. All received cyclophosphamide, 57 with fractionated total body irradiation, and 13 with BCNU and cytarabine. Hematologic engraftment was prompt and unaffected by phenotype (B vs. T) or by in vitro purging used (B vs. T vs. none) although nine of 16 non-relapse deaths were related to poor graft function. Fifty-one patients (73%) were alive in complete remission (CR) 1 month following transplantation while 15 patients (12 with initially refractory disease) had persistent disease. Subsequently, 41 +/- 18% (by Kaplan-Meier estimate; +/- 95% confidence limits) of those who achieved CR remained relapse free 1-6.4 (median 3) years post-BMT. Neither risk group, purging, nor immunophenotype predicted subsequent post-transplant relapse. Among those 51 who achieved CR, 13 of 43 (27 +/- 14%) with responsive disease survive disease free while three of eight (38 +/ 34%) refractory patients survive disease free (p = 0.96). Overall, 24 patients survive, 16 in continuous complete remission 1-6.5 years following transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933058 TI - Cutaneous mastocytosis after autologous bone marrow transplantation. AB - A 41-year-old male patient developed cutaneous mastocytosis 3 months after autologous bone marrow transplantation (ABMT). The ABMT was performed as part of consolidation treatment for a high-grade malignant non-Hodgkin's lymphoma. There was no evidence for systemic mastocytosis. Recurrence of the lymphoma could not be shown. Mast cell proliferation frequently coexists with dysplastic and neoplastic disorders of myeloid and, more rarely, of lymphoid cells. Mast cells are growth factor responsive and ultimately originate from the pluripotent hematopoietic stem cell. After autologous bone marrow transplantation, hematological reconstitution may in rare cases lead to an abnormal proliferation of mast cells possibly due to unbalanced production of growth factors. PMID- 1933057 TI - Hepatic veno-occlusive disease in a patient with lupus anticoagulant after allogeneic bone marrow transplantation. AB - A 37-year-old man with acute myeloblastic leukemia (FAB M2) in first remission underwent a bone marrow transplant (BMT) following conditioning with high-dose cytarabine and total body irradiation. The donor was an HLA-identical brother. Graft rejection occurred and a second BMT was performed from the same donor following conditioning with cyclophosphamide. Engraftment was achieved, but the patient developed severe jaundice and died of respiratory failure on day +46 after the second BMT. Liver biopsy revealed luminal narrowing of the central veins and a diagnosis of hepatic veno-occlusive disease (VOD) was made. The coagulation studies showed a prolonged kaolin clotting time which was not corrected by 1:1 mixture with normal plasma, and the platelet neutralization test was positive. Dilute tissue thromboplastin time and dilute Russell viper venom time were also prolonged. These results fulfilled the criteria for lupus anticoagulant, which may have contributed to VOD in this patient. PMID- 1933059 TI - Liposomal amphotericin B and erythrocyte echinocytosis. PMID- 1933060 TI - Incidence of HLA-DPB1 mismatches in HLA-A, B and DR serologically matched bone marrow transplant pairs, as detected by PCR-SSOP. PMID- 1933062 TI - Questions in marrow matching: the implications of ancestral haplotypes for routine practice. PMID- 1933061 TI - Bone marrow transplantation for severe aplastic anemia. AB - Allogeneic marrow transplantation from an HLA-identical sibling has proven to be an effective treatment for severe aplastic anemia with restoration of normal hematopoiesis and long-term survival in 70-80% of recipients. Results are related to patient age, with improved survival in younger patients. Marrow transplantation from HLA nonidentical family and unrelated donors has been less successful and is the focus of ongoing clinical research. Graft rejection and graft-versus-host disease (GVHD) remain major problems. A number of pre- and post transplant immunosuppressive regimens to prevent these complications continue to be studied. The risk of graft rejection is increased in patients who have been transfused before transplant, whereas the risk is decreased with the infusion of larger numbers of transplanted marrow cells. The incidence of graft rejection is 10-32% when cyclophosphamide is used alone as the pretransplant conditioning regimen. The addition of donor buffy coat cells and whole body or limited field radiation have reduced the rate of graft rejection, but increased the incidence of complications such as chronic GVHD and secondary malignancies. GVHD is an immune disorder caused by incompatibility between donor and recipient for histocompatibility antigens. Approximately 18-40% of patients experience moderate to severe acute GVHD. Previous pregnancy in female donors and increasing age of the patient are factors predictive of its development. Methotrexate and cyclosporin have been used most frequently as prophylactic immunosuppressive agents; various combinations of these drugs and prednisone are being evaluated. Symptomatic chronic GVHD occurs in approximately 25% of recipients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933063 TI - Bone marrow transplantation in children using closely matched related and unrelated donors. AB - Seventeen bone marrow transplants were undertaken on 15 patients with leukemia or aplastic anemia using marrow from closely matched (phenotypic or five out of six HLA-A, B and DR antigen matched related and unrelated) donors. Donors were siblings (four), parents (seven), aunt (one), great aunt (one) or matched unrelated (two). When compared with transplants using matched sibling donors, survival was not different (51.4 +/- 13.4% vs. 48.1 +/- 9.6%; p = 0.87) but transplant-related complications and morbidity were higher as follows: graft versus-host disease (GVHD) (87% vs. 15%; p less than 0.001), interstitial pneumonitis (59% vs. 14%; p less than 0.003), days in hospital (51 vs. 26; p less than 0.001), and chronic transplant related morbidity 50% vs. 11%; p + 0.033). The age of donors who were closely matched was significantly greater than that of their recipients (29.7 +/- 13.9 years vs. 8.1 +/- 3.1 years; p less than 0.001) and was associated with poorer transplant outcome. Median transplant-related complication-free survival for patients receiving transplants from age non disparate donors was 53 months (range 18-86 months) compared with 12 months (range 2-42 months) for age disparate donors (p = 0.028). Transplants from closely matched donors were undertaken in the ratio of one to every three matched donors, indicating the importance of this source of marrow in a transplant program. PMID- 1933064 TI - Treatment of aGVHD with OKT3: clinical outcome and side-effects associated with release of TNF alpha. AB - Monoclonal antibodies are increasingly used for treatment of acute graft-versus host disease (aGVHD) in bone marrow transplantation. We treated seven patients with steroid resistant aGVHD with the monoclonal anti-T cell antibody OKT3. Though five patients showed improvement of aGVHD, only two became long-term survivors. OKT3 treatment was accompanied by deterioration of microangiopathy and prolonged increase of tumor-necrosis-factor alpha serum levels indicating activation of monocytes/macrophages in vivo, as this was not observed in a control group of patients receiving anti-T cell globulin. These findings may be related to immunostimulatory activity reported for OKT3 in vitro. Strategies interfering with cytokine release should improve clinical results of OKT3 treatment. PMID- 1933065 TI - [Insular modifications in glycerophosphate dehydrogenase in diabetes]. AB - In the model of non-insulin-dependent diabetes found in adult rats injected with streptozotocin during the neonatal period, the activity of the mitochondrial glycerophosphate dehydrogenase is severely reduced in pancreatic islets. This coincides with a decreased contribution of aerobic to total glycolysis in intact islets and could account for the preferential impairment of the insulin secretory response to glucose. PMID- 1933067 TI - Current update on OSHA regulations. PMID- 1933066 TI - [Development of a campaign strategy against malaria in a rice-growing region of Burundi]. AB - Epidemiological studies undertaken in an area of low altitude in Burundi, revealed microgeographic variations of malaria endemicity, naturally unstable in the area. However transmission is relatively high near rice fields. The transmission increases at the end of the rainy season, period of natural decrease of the vector population combined with an increase of their longevity. Indoor spraying with short acting insecticides during that period of the year, reduced considerably the transmission and high parasitaemia in children, without changing the susceptibility of the vector to the insecticide. PMID- 1933068 TI - The historiography of medical history: from great men to archaeology. AB - The history of medicine is always written from the basis of the historian. Contemporary historiography provides an understanding of the major methods of historical analysis and their influences on the writing of medical history. Medical history in the 20th century has emphasized the historiographic methods of the history of great men, historicism, social history, and intellectual history. Each methodology has inherent biases that influence the historian's analysis of the past. Understanding the historian's biases provides the reader important tools for the interpretation of medical history. PMID- 1933069 TI - Medical care at the Siege of Vicksburg, 1863. PMID- 1933071 TI - Thomas Hodgkin and Moses Montefiore; Europe, Asia, and Africa. PMID- 1933070 TI - Epidemic diseases at the New York Hospital. AB - The New York Hospital has enjoyed a long, rich history in the development of American health care. AIDS has made relevant an understanding of the failures and successes achieved during past epidemics. Innovations in disease prevention and patient care have been essential in the conquest of pestilence. However, public indifference toward the people at greatest risk for these diseases has traditionally delayed attempts to prevent significant loss of life and socioeconomic destruction. PMID- 1933072 TI - The evolution of surgery at the New York Hospital. AB - Surgery evolved from colonial times through many innovations and developments. During this time it was transformed from a dangerous practice to a delicate and scientific art. Many of these early developments continue to be a part of modern surgical therapy. Although European discoveries have had a profound effect on this evolution, American advances solidified the link between the laboratory and the operating room. The New York Hospital-Cornell Medical Center, like other medical centers around the country, made important contributions to this evolution. Because the hospital has spanned American history, it also has paralleled surgical development in the United States. PMID- 1933073 TI - The delayed neurobehavioural sequelae of traumatic brain injury. AB - This is a comprehensive review of the late-occurring effects of traumatic brain injury (TBI). It appears that TBI increases the risk over basal rates for the general population, to this degree: for depression, by a factor of five or 10; for seizures, by two to five; for psychotic disorders, by the same factor; and for dementia, by four or five. Severe TBI, or injuries with special characteristics, may increase the risk of delayed sequelae even further. One is not able, at this point, to estimate the relative occurrence of a newly described entity--delayed amnesia. An initial TBI increases the risk for subsequent TBI, by a factor of two. A second TBI increases the risk of yet another TBI eightfold. PMID- 1933074 TI - Somatosensory evoked potentials in prolonged postcomatose unawareness state following traumatic brain injury. AB - Somatosensory evoked potentials (SEPs) were found by several authors to have a prognostic value in traumatically brain-injured (TBI) patients and can serve for monitoring changes in the state of TBI patients. Most of the studies were performed in the acute phase of trauma and most of reports have dealt with the short-latency components. The present study reports on seven patients (mean age 26.2 years) who suffered severe blunt TBI and were in prolonged post-comatose unawareness (PCU) state, in whom early and late SEP components were recorded at least 5 weeks after sustaining trauma. The SEPs studied could not reveal a uniform pattern apart from prolonged central conduction time (CCT), which was common to all patients. This may be due to individual non-homogeneous patterns of brain damage in our severe TBI patients. Meaningful late recovery of consciousness occurred in one patient and correlated with shortening of CCT. We suggest that the prolonged CCT found in our patients is related to diffuse subcortical axonal injury and that the shortened CCT found during the second examination in this patient actually reflects late partial recovery--either structural or functional--of affected brain regions. This patient is also an example of the possible relationship between reduction of CCT and recovery of consciousness a long time after injury. PMID- 1933075 TI - Improving executive function disorders in brain-injured clients. AB - In 1983, Lezak described executive functioning as the ability to engage in independent, purposeful, self-directive and self-serving behaviour. Self initiation, problem-solving and self-monitoring or regulation of behaviour are important components of executive functioning. This paper presents the results of efforts to improve executive functioning in three areas: problem solving, self initiation and self-regulation. PMID- 1933076 TI - Some guidelines for family therapists working with the traumatically brain injured and their families. AB - A summary is presented of the major sequelae of traumatic brain injury and of the effects of these on the individual and the family. A series of guidelines is offered for use by family therapists when working with this population. The therapists must be directive, informed and informing. At times the therapist is an advocate, a model, a monitor and an agent of generalization. PMID- 1933077 TI - The use of the MCMI in the personality assessment of head-injured adults. AB - MCMI (Millon Clinical Multiaxial Inventory) profiles of 79 head-injured patients were compared with self-report of personality change following head injury. Mean MCMI scale scores were highest on Scales D (Dysthymia), A (Anxiety), 6 (Antisocial), H (Somatoform), 5 (Narcissistic) and 7 (Compulsive). Taking only high-point codes above an adjusted base-rate score of 75, the sample showed most frequent elevations on A (Anxiety), D (Dysthymia), H (Somatoform), 5 (Narcissistic), 6 (Antisocial-Aggressive) and 8 (Passive-Aggressive), in order of cumulative frequency. Personality trait scales and clinical scales were compared with self-report of personality changes. Elevated personality trait scales correlated with self-reports of dysfunction and so did clinical scale elevations. There was no relationship between the number of elevated scales and severity of head injury, nor between the number of elevated scales and interval after head injury. PMID- 1933079 TI - Psychosexual and psychosocial sequelae of closed head injury. AB - A series of 36 patients who had been hospitalized following closed head injury (CHI) were followed up 4.06 (SD 3.71) years after the injury. Measures were taken of degree of psychosexual dysfunction (Golombok Rust Inventory of Sexual Satisfaction-GRISS), general psychiatric morbidity (General Health Questionnaire GHQ), and clinical anxiety and depression (Hospital Anxiety and Depression Scale HAD). These measures were completed by patients and partners. Resulting data revealed that 50% of male patients with current sexual partners produced psychosexual profiles that fell within the dysfunctional range. For both male patients and their partners, the chief psychosexual complaint was infrequency. Of the patients studied, 61% were classified (using the GHQ) as having degrees of emotional distress that would fall within the range of psychiatric 'caseness', while 25% of patients achieved HAD criteria for clinical anxiety and 22% met HAD criteria for depression. Of the partners, 41% met GHQ criteria for psychiatric 'caseness', 18% being classified using the HAD as anxiety cases and 6% as depression cases. No effects of severity of injury were observed on any of the main outcome measures. Age and time since injury were related to measures of psychosexual dysfunction. These results are discussed in relation to the existing literature on psychosocial outcome in closed head injury, and recommendations for therapeutic intervention are made. PMID- 1933078 TI - The use of adapted leisure materials to reinforce correct head positioning in a brain-injured adult. AB - This study aims to highlight the possible use of adapted leisure materials in the modification of behavioural responses within the brain-injured population. Single case methodology was used to evaluate the effectiveness of contingent reinforcement in promoting head posture in an adult brain-injured male. A microswitch was implanted within a headband worn by the subject, attached to a portable radio and positioned such that correct head posture operated the switch, completed the electric circuit and activated the music. The target behaviour was defined as the percentage of time in a walking programme where correct head posture was maintained. The experimental procedure incorporated an A-BC-B-BC-A design and represented the following phases: (A) baseline; (BC) headband + music and (B) headband, no music. A follow-up assessment was also undertaken 1 month later. Overall, statistical analysis revealed a significant increase in the target behaviour and that this improvement was directly contingent on the provision of music inforcement. Results are discussed in further detail and the clinical significance of this finding, over and above the statistical significance, is highlighted in terms of this individual's rehabilitation. PMID- 1933080 TI - The Visual Response Evaluation: a pilot study of an evaluation tool for assessing visual responses in low-level brain-injured patients. AB - The Visual Response Evaluation (VRE) was developed to meet the need for a formal and in-depth measure of visual responses in low-level brain-injured persons (Rancho Levels II and III) and to monitor and document minute changes in the recovery of these patients. Often, patients at these low functional levels exhibit little to no motoric or cognitive interaction with the environment, except that which occurs in response to sensory stimulation. Other tools have been developed to document responses to various types of stimulation; however, none contain the sensitivity to consistency and type of response that is necessary to show the small but vital progress that is characteristic of the Rancho II and II type patient. The VRE consists of 10 items separated into two general categories: (1) Observations. and (2) Response to Stimuli. The five items in the Observations section assess a patient's spontaneous responses, while the five items in the Response to Stimuli section document responses directly related to the presentation of a hierarchical order of stimuli. The VRE was administered to 10 patients with a mean age of 39.8 years at a mean time of 4.2 months post injury. Statistical analyses of the pilot-study data show the VRE to be both internally reliable and criterion-related valid at the p less than 0.025 level of significance. The data supports further investigation in the areas of prognostic ability and implications for treatment. The VRE can be a useful tool for studying the recovery process and evaluating treatment programmes for low-level brain injured persons. PMID- 1933081 TI - Memory notebook training with traumatically brain-injured clients. AB - Four brain-injured clients continually demonstrated short-term memory deficits including difficulty learning new material and forgetting appointments. Training in the use of memory notebooks improved performance of homework assignments and keeping appointments. PMID- 1933082 TI - Pharmacology and flexibility in the rehabilitation of two brain-injured adults. PMID- 1933083 TI - Biopercular lesions and acquired mutism in a young patient. AB - A 13-year-old patient developed complete mutism and buccofacial apraxia following toxic vasculitis due to a yellow scorpion sting. Language functions were preserved. A CT scan disclosed mainly biopercular infarcts. It is suggested that the lost control of vocalization and speech is associated with biopercular lesions and that a preserved right opercular region can take over this function in the presence of damage to homologous left opercular region. PMID- 1933084 TI - Communication from China. PMID- 1933085 TI - The safe Medical Devices Act of 1990--a look at the implications. Interview by Larry Tanner. PMID- 1933086 TI - Clinical involvement of biomedical specialists in neonatal extracorporeal membrane oxygenation (ECMO). PMID- 1933087 TI - Laser maintenance and safety precautions. PMID- 1933088 TI - New adventures in biomedical engineering: radiation safety program management. AB - As biomedical/clinical engineers expand their managerial expertise into nontraditional areas, it makes sense that they pursue areas where their formal training in physics and mathematics can be applied. Radiation safety requires having the educational background to understand atomic structure, the nature of radioactivity, mathematics, biology, chemistry, and instrumentation. Program management requires having the administrative experience to manage people, data, files, documentation, and budgets. Radiation safety program management also requires an understanding of how best to prepare for a surprise inspection, similar to but technically more specific than other inspections and surveys previously experienced by the BME/CE professional. PMID- 1933090 TI - Performances of potentially implantable rechargeable glucose sensors in vitro at body temperature. AB - The authors developed a glucose sensor that operates in vitro at 37 degrees C for at least three months without recharging. The use of fine carbon particles upon which to immobilize the glucose oxidase makes it possible to recharge the sensor when enzymatic activity diminishes. This may enable the sensor to perform for at least a year when implanted, and thus reduce the frequency of surgical replacement. Recharging is accomplished by inserting a hypodermic needle into the septum of an implanted reservoir. Three types of carbon were investigated: graphite powder, carbon lamp black, and low-temperature isotropic carbon powder (ULTI). Two cross-linking procedures were tested. The sensor that remained operational for the longest time used the ULTI and the cross-linking procedure that mixed the enzyme, immobilized on carbon powder, with albumin and glutaraldehyde. This sensor operated continuously at 37 degrees C for at least three months. Further, it was put through four recharge cycles with ten days of successful operation after each without change. The sensor is very stable and the results obtained with it are reproducible. PMID- 1933089 TI - Detection of ventricular fibrillation with a ventricular monopolar catheter electrode. AB - This report describes the use of right ventricular impedance (RVZ) sensing with a monopolar electrode to identify the cessation of pumping with the onset of ventricular fibrillation. RVZ, ECG (lead II), and femoral artery pressure were monitored in seven anesthetized dogs. An impedance recorder (10-kHz, 100-microA peak-to-peak current) was used to measure RVZ between a monopolar, catheter mounted electrode placed in the right ventricle and an indifferent electrode (8.5 cm diameter plate) sutured to the right chest wall. The catheter electrode was either 0.4 cm or 1.2 cm long and had a surface area of 0.50 cm2 or 1.50 cm2, respectively. A monopolar electrode was positioned at the apex of the right ventricle or midway between the apex and the tricuspid valve. The peak-to-peak amplitude of the pulsatile cardiac-induced impedance change was measured prior to and throughout an episode of ventricular fibrillation lasting up to 1 minute. On the average, the amplitude of the pulsatile RVZ signal after 10 seconds of fibrillation decreased by 79% of the prefibrillation amplitude. The 1.2-cm electrode located at the middle of the ventricle showed the largest reduction in pulsatile impedance, the amplitude being very small at 10 seconds. It is concluded that sensing RVZ by a monopolar electrode located on a catheter in the mid-ventricle can provide the mechanical information needed to identify the onset of ventricular fibrillation. PMID- 1933091 TI - Application of piezo film technology for the quantitative assessment of pruritus. AB - A method to quantitate scratching has been developed for assessing the efficacies of interventions purported to ameliorate pruritus. The technique employs a piezo film sensor attached to the finger and the supporting electronics to amplify, transmit, and process the signals generated by the piezo film. The piezo film is essentially a contact microphone on the fingernail of the scratching subject. The method is currently incorporated into clinical trials, and preliminary results are promising. PMID- 1933092 TI - No fault compensation. PMID- 1933093 TI - Consultation liaison psychiatry. PMID- 1933095 TI - Definitions of disc disease. PMID- 1933096 TI - The scientific approach to a giant ovarian cyst. PMID- 1933094 TI - Counsel and care. PMID- 1933097 TI - Diagnosis and treatment of ocular melanomas. AB - Ocular melanomas pose a serious threat to both sight and survival. In recent years, new approaches to their diagnosis and treatment have been developed. While these have, in many instances, preserved patients' vision, overall survival has remained unaltered. These new approaches will be discussed together with an overview of current research. PMID- 1933098 TI - Management of epilepsy in childhood. AB - Epilepsy is the commonest neurological disorder of children. Between 0.5 and 1% of the childhood population is affected either temporarily or chronically. In the individual it is important to be certain that the diagnosis is correct and thereafter to classify the seizure type(s) and, if possible, the epileptic syndrome. This will facilitate optimal therapeutic intervention and rational management of any associated problems. PMID- 1933099 TI - The current state of positron emission tomography. AB - Positron emission tomography (PET) allows the construction of functional images, and has research and clinical applications particularly in cardiology, oncology and the neurological sciences. In the next 5 years PET scanners will become more available to clinicians, while methodological refinements should lead to exciting breakthroughs, especially in our understanding of neurology and psychiatry. PMID- 1933100 TI - Preparing for postgraduate examinations. AB - Nearly all junior doctors have to revise for and take postgraduate examinations while doing busy hospital jobs with nights and weekends on call. The pass rates vary for different postgraduate examinations, but are all much lower than for medical school finals. For many young doctors, this will be their first experience of examination failure and is consequently harder to deal with. PMID- 1933101 TI - How to perform a temporal artery biopsy. AB - Temporal artery biopsy is performed to confirm the diagnosis of giant cell arteritis. The technique is described together with the anatomy of the superficial temporal artery. PMID- 1933102 TI - Erlenmeyer flask-shaped long bones. AB - Radiological terminology includes a number of interesting and often amusing terms intended to help us understand and remember the pathological abnormality being described. What radiological sign is illustrated in Fig. 1 and what condition does it represent? PMID- 1933103 TI - Acting as a medical expert in medical negligence cases. AB - With the rise in the number of medical negligence claims over the last decade the demand on doctors to act as medical experts has correspondingly increased. This article reviews the criteria necessary to be a credible expert witness and gives guidance on writing a report that will stand the test of legal scrutiny. PMID- 1933104 TI - A solitary thyroid nodule. PMID- 1933105 TI - Awake fibreoptic intubation. PMID- 1933106 TI - Consensus on high-density lipoprotein. PMID- 1933107 TI - Mandibular reconstruction using a free vascularised osteocutaneous flap from the internal condyle of the femur. AB - The authors present a preliminary report of a new microsurgical mandibular reconstruction procedure using a segment of the internal condyle of the femur as a free vascularised bone graft. It is possible to harvest a compound flap including a bony segment measuring 8 X 1.5 X 1.5 cm and a cutaneous saphenous flap with its nutrient pedicle arising from the descending genicular artery and vein. This surgical procedure provides a good cortico-cancellous bony segment and a separate skin flap. Dissection of the flap is sometimes difficult due to the inconsistency of its vascular anatomy; the donor site is left with minimal morbidity but, because of weakening of the femur, our patients are instructed not to return to full weight-bearing before the sixth postoperative week. We consider segmental reconstruction of the mandibular body to be one of the best indications for the flap. PMID- 1933109 TI - Correction of cryptotia using a subcutaneous pedicled flap. AB - Cryptotia is a relatively common deformity of the ear among orientals. Although many methods for correcting this deformity have been reported, there is no one perfect method. We have developed a method using a subcutaneous pedicle flap raised from the retroauricular region, where relative abundance of skin exists. We have treated 9 ears of 7 patients by the method reported herein. Results are satisfactory in all cases. PMID- 1933108 TI - Sternoclavicular joint swellings: diagnosis and management. AB - Five patients with sternoclavicular swellings are described. The group presents a variety of diagnoses which highlight the need for thorough investigation and appropriate management of swellings around the sternoclavicular joint. Although frequently assumed to be benign, this series demonstrates the potential occurrence of malignant disease, and the dangers of pursuing a simple conservative course. Conversely, a substantiated benign diagnosis may avoid the use of unnecessary surgical treatment. PMID- 1933110 TI - Temporomandibular arthroplasty by pedicled transfer of the sternoclavicular joint -a simplified technique. AB - One of the options available for the treatment of temporomandibular ankylosis is the replacement of the joint by the sternoclavicular joint pedicled on neck muscles. This paper describes a modified technique of pedicled sternoclavicular joint transfer and evaluates its advantages. PMID- 1933111 TI - Treatment of drooling by parotid duct ligation and submandibular duct diversion. AB - A new combination of operations is described for controlling drooling in patients with cerebral palsy. Fourteen patients underwent ligation of one parotid duct and diversion of both submandibular ducts at the same operation. Drooling was controlled in all. Transient oro-facial swelling was the commonest complication. PMID- 1933112 TI - The extensibility in human skin: variation according to age and site. AB - Normal skin extensibility in the living body of 94 healthy male subjects ranging in age from 3 months to 73 years was determined quantitatively with the Bio-Skin Tension Meter at 12 sites. In comparison with the age of 20-29 years, the skin extensibility, particularly in the age group of less than 2 years, was significantly high. However, no significant difference from the age groups of 12 14, 15-19, 30-49 and over 50 years was found at any site. Correlation by age was noted at the extremities, excluding the posterior upper arm and at the lower abdomen, with the extensibility of the group less than 1 year as the maximum value, decreasing gradually down to 3-5 or 6-8 years. At the cheek, shoulder, anterior chest, and posterior upper arm, however, no correlation with age was noted. PMID- 1933113 TI - Microvascular tissue transfer in paediatric patients: analysis of 106 cases. AB - We report a series of 106 microvascular transplants performed in paediatric patients between 1973 and 1989. Eighty-eight percent of these flaps were successful. Two of the 13 failed flaps (1.9%) in this series were lost because of small vessel size. Otherwise, success rates (93% in the last 5 years) and complications were comparable to our adult cases. No growth-related complications were noted either in recipient or donor sites. We conclude that microvascular transplantation is a reliable procedure in children. PMID- 1933114 TI - Enhanced healing of 30 microns Gore-Tex PTFE microarterial prostheses by alcohol pretreatment. AB - Polytetrafluoroethylene (PTFE) microvascular prostheses with a fibril length of 30 microns were pretreated with alcohol (n = 18), implanted into the abdominal aorta of rats and were evaluated at 1 day (n = 3), 1 week (n = 3), 3 weeks (n = 6) and 6 weeks (n = 6) to determine whether alcohol-pretreatment might improve their healing. Untreated PTFE microvascular prostheses (n = 18) functioned as controls (all prostheses: length 10 mm, I.D. 1.5 mm). The alcohol-pretreated PTFE microarterial prostheses were initially completely filled and covered with clot and showed fast and complete healing within 6 weeks: endothelial cells and smooth muscle cells on the luminal surface, and the interstices filled with fibrous-like tissue. In contrast, the untreated PTFE prostheses were initially not filled or covered with clot and showed only healing near the anastomotic sites and scarce tissue ingrowth into the wall. These results demonstrate that alcohol pretreatment improves the healing characteristics of PTFE microarterial prostheses with a fibril length of 30 microns. The alcohol-pretreatment renders the PTFE material more accessible to clot and subsequently to cells. PMID- 1933115 TI - Vesicant burns. AB - (1) Of the 120,000 victims of sulphur mustard gas in World War I there were only 2-3% fatalities, and few long term effects. (2) The interactions of sulphur mustard with the skin are complete within a few minutes of exposure. Once the victim has been decontaminated there is no risk to the attendant and there is no active agent in the blister fluid. (3) The rate of wound healing is slow for sulphur mustard burns, but in general the wounds heal satisfactorily. (4) There is no specific therapy for poisoning by sulphur mustard. PMID- 1933116 TI - Textured or smooth implants for breast augmentation? A prospective controlled trial. AB - This study examines the hypothesis that textured surface silicone implants reduce the incidence of adverse capsular contracture in breast augmentation. A total of 53 patients were entered into a prospective study; they were randomly assigned to receive either smooth or textured implants which were placed in the submammary plane. Of these, 50 patients were assessed at 12 months by a panel of observers who did not know which type of implants had been used. Adverse capsular contracture (Baker grades 3 and 4) was found in 28 breasts augmented with smooth surface implants (58%) and in 4 breasts in the textured surface implant group (8%). This reduction in adverse contracture using textured surface implants was highly significant (p less than 0.0001). Careful trial design is essential in studies of this sort in order that we can obtain useful data regarding the causes and prevention of adverse capsular contracture. PMID- 1933117 TI - Further experience with the posterior interosseous flap. AB - This paper describes and discusses some of the clinical applications of the posterior interosseous forearm flap in hand reconstruction, including the fact that larger areas of skin than previously reported can be used safely. It is based on a series of 21 patients, 50 anatomical dissections and 10 injection studies. PMID- 1933118 TI - Free second toe transfer for reconstruction of the distal phalanx of the fingers. AB - Free transfers of the distal parts of the second toe for reconstruction of distal phalangeal losses of the fingers were successfully carried out. This method is believed to be the best for functional and cosmetic reasons, but major postoperative vascular problems exist. To overcome these problems, multiple vascular anastomoses were employed at operation. The indications for this method are limited in Japanese patients, and its use depends on the patient's age, sex, religious beliefs and the shape of the second toe. PMID- 1933119 TI - Technical refinement of the lateral supramalleolar flap. AB - The lateral supramalleolar flap has proved to be versatile for managing a variety of skin defects of the foot, ankle and lower third of the leg. An anatomical study has shown the reliability of a subcutaneous vascular network, supplied by terminal branches of the perforating branch of the peroneal artery. Our technical refinement consists in designing the skin flap more proximally on the lateral aspect of the leg, and mobilising it on its vascular fascio-subcutaneous pedicle. The flap provides considerable possibilities for covering more distal skin defects of the lower extremity. PMID- 1933120 TI - A well developed alveolabial sulcus of the intermaxilla in a complete bilateral cleft lip and palate. AB - An uncommon well developed alveolabial sulcus in a baby born with a complete bilateral cleft lip and palate is presented. The possible embryonic explanation for this extremely rare finding is discussed. PMID- 1933121 TI - Recurrent orf in an immunocompromised host. AB - A 30-year-old farmer with Nezelof's syndrome developed a giant orf on his hand. Recurrence followed surgical excision. Three excisions and split skin grafts were required before its eradication. He re-presented 8 years later with a further orf on the finger of his opposite hand. This lesion had not grown to the exuberant proportion of the previous lesion, but it defied repeated excisions, and various medical therapies including idoxuridine, interferon and transfer factor. Excision with hypochlorite dressings perioperatively and delayed split skin grafting led to eventual eradication. PMID- 1933122 TI - Duplication of the upper lip and maxilla. AB - We report a patient with duplication of the upper lip and maxilla. This deformity is extremely rare and six previous reports are reviewed. PMID- 1933123 TI - Local anaesthetics in dental cartridges. PMID- 1933125 TI - A modified needleholder for microsurgery--reply. PMID- 1933124 TI - Removal of unwanted tattoos. PMID- 1933126 TI - Prefabrication of thin transferable axial-patterned skin flaps. PMID- 1933127 TI - Prostaglandin E1 decreases the low-density-lipoprotein entry into rabbit arterial wall. AB - 1. In 72 male rabbits fed a 1% cholesterol supplemented diet the effect of a 4 weeks daily infusion of prostaglandin E1 (PGE1, 20 micrograms kg-1 min-1 over 2 h) on [125I]-low density lipoprotein (LDL) accumulation (10 microCi; 0.5 mg protein ml-1) was examined versus sham-treatment after removal of the endothelium of the abdominal aorta by a Fogarthy catheter. 2. The uptake of [125I]-LDL was significantly (P less than 0.01) higher in endothelium-free aortic segments (showing the highest peak maximum at around 12 h after 125I-injection) as compared to aortic segments with endothelium intact (showing the lowest uptake of [125I]-LDL with the peak maximum at 48 h, last control time). Segments with the endothelium restored showed a similar LDL-retention curve to segments with endothelium however, being again significantly (P less than 0.01) higher. 3. PGE1 treatment caused reduction in LDL-accumulation, being significantly (P less than 0.001) pronounced in segments without endothelium and in segments with endothelium restored. 4. The findings indicate a beneficial effect of PGE1 in lipid metabolism by decreasing the LDL-influx into the arterial wall in-vivo. PMID- 1933128 TI - Possible role of leukotrienes in hypoxic contraction of canine isolated basilar artery. AB - 1. Hypoxia reversibly increased isometric tension in unstimulated canine isolated basilar artery rings. 2. Nordihydroguaiaretic acid (NDGA; 5 x 10(-6) M), an inhibitor of lipoxygenase and quinacrine (10(-5) M), which blocks the release of arachidonic acid from phospholipids by inhibiting the enzyme phospholipase A2, blocked hypoxia-induced contractions. 3. The preferential leukotriene D4 (LTD4) antagonist, L-660,711, also inhibited the hypoxia-induced contractions in concentrations ranging from 10(-8) M to 10(-5) M. The effects seen were statistically significant (P less than 0.05). Two components of inhibition were seen. 4. Arachidonic acid (5 micrograms ml-1) caused contraction of the isolated basilar artery rings. This response was inhibited by NDGA (5 x 10(-6) M) and L 660,711 (10(-5) M). 5. The LTD4 (10(-8) M-10(-7) M)-induced contraction was relaxed by L-660,711 in a dose-dependent manner. Both the contraction caused by LTD4 as well as that caused by hypoxia were relaxed by 5 x 10(-6) M adenosine. 6. Leukotriene(s) may be involved in hypoxia-induced contraction of canine isolated basilar artery. However, they may not be the sole mediator(s). PMID- 1933129 TI - Pharmacological modulation of endothelin-induced contraction of guinea-pig isolated airways and thromboxane release. AB - 1. The aim of the present experiments was to study the possible involvement of known bronchoconstrictor substances in mediating the myotropic action of endothelin-1 (ET-1, human-porcine endothelin) in guinea-pig isolated airways. 2. ET-1 (1-100 nM) caused a dose-dependent contraction of guinea-pig trachea, upper bronchus and parenchyma. The contractions developed slowly, reaching maximal values 4-6 min after addition of the peptide. 3. The contractile action of ET-1 was significantly attenuated by indomethacin (10 microM), a cyclo-oxygenase blocker. BM 13505 (5 microM), a thromboxane receptor antagonist, FPL 55712 (19 microM) and YM 16638 (1 microM), antagonists of the sulphidopeptide leukotrienes, BN 52021 (10 microM) and WEB 2086 (1 microM), platelet-activating factor receptor antagonists in all three tissue preparations studied. 4. Pretreatment of the airway tissues with compound U 75302 (3 microM), a selective leukotriene B4 receptor antagonist, or with a mixture of antagonists containing methysergide (0.75 microM), phentolamine (0.4 microM), propranolol (13 microM), atropine (0.4 microM) and diphenhydramine (0.45 microM) did not modify the myotropic action of ET-1. 5. ET-1, 10 and 100 nM induced three, and nine fold increases in thromboxane A2 release from lung parenchymal strips. 6. ET-1-induced thromboxane A2 release was completely abolished by indomethacin, and was significantly attenuated by BN 52021, WEB 2086 and FPL 55712. Neither BM 13505 nor YM 16638 exerted a significant effect on thromboxane release. 7. The present findings show that contraction of guinea-pig airway smooth muscle by ET-1 is mediated, in part, by the release of thromboxane A2, sulphidopeptide leukotrienes and platelet activating factor, and suggest that the increased thromboxane A2 release following ET-1 is partly a consequence of enhanced synthesis of sulphidopeptide leukotrienes and platelet-activating factor. PMID- 1933130 TI - Excretion of metabolites of prostacyclin and thromboxane by rats with nephrotoxic nephritis: effects of interleukin-1. AB - 1. To obtain direct evidence of abnormal eicosanoid biosynthesis in rats injected with anti-glomerular-basement-membrane antibodies (a-GBM), products derived from thromboxane A2 (TXA2) and prostacyclin (PGI2) were measured in 24 h urine collections before and after a-GBM. 2. Administration of a-GBM (9.5 mg) caused albuminuria, decreased creatinine clearance, increased numbers of intra glomerular neutrophils and increased excretion of TXB2, 2,3-dinor-TXB2 (products of TXA2) and 6-oxo-PGF 1 alpha and 2,3-dinor-6-oxo-PGF 1 alpha (products of PGI2) at 24 h. 3. Interleukin-1 (IL-1 beta; 5 micrograms) alone caused an increase in PGI2 metabolite excretion but had no effect on TXA2 metabolites. It had no effect on creatinine clearance but increased numbers of glomerular neutrophils by approximately 4-5 fold compared to a-GBM. 4. Pretreatment of rats with IL-1 beta before a-GBM synergistically increased albumin excretion but only additively increased eicosanoid excretion. Numbers of intra-glomerular neutrophils and creatinine clearance were unchanged compared to IL-1 beta alone. 5. The cyclo oxygenase inhibitor, ibuprofen (10 mgkg-1 i.p., twice daily for 4 days) inhibited both serum TXB2 production and urinary prostaglandin excretion. It also caused an almost complete attenuation of albumin excretion. Creatinine clearance and glomerular neutrophils remained unchanged after a-GBM/IL-1 beta. 6. We conclude that the 50% inhibition of thromboxane production induced by ibuprofen does not modify the fall in creatinine clearance of accumulation of neutrophils in the glomerulus caused by the a-GBM. This degree of inhibition of eicosanoid production was associated with a striking decrease in proteinuria, but this may reflect a haemodynamic rather than a disease modifying action. PMID- 1933131 TI - Nitrendipine, given during drinking, decreases the electrophysiological changes in the isolated hippocampal slice, seen during ethanol withdrawal. AB - 1. Extracellular recordings were made from mouse isolated hippocampal slices prepared after chronic treatment in vivo with either ethanol or ethanol plus the dihydropyridine calcium channel antagonist, nitrendipine. 2. The withdrawal of ethanol caused a variety of changes in the field potentials, as previously reported, including decreases in the thresholds for eliciting single and multiple population spikes, increases in paired pulse potentiation and shifts to the left of the input/output curves. 3. The addition of nitrendipine to the drinking mixture in the chronic ethanol treatment significantly decreased all the changes in the field potentials that were seen after ethanol withdrawal. 4. Addition of nitrendipine to the perfusion medium also decreased the signs of hyperexcitability seen in the hippocampal slices during ethanol withdrawal. 5. The results provide further evidence that neuronal calcium channels may be involved in ethanol dependence and that the adaptive changes caused by chronic ethanol treatment can be modulated by alterations at dihydropyridine-sensitive sites. PMID- 1933132 TI - Comparison of the haemodynamic effects of adenosine monophosphate with sodium nitroprusside in a canine model of acute global left ventricular dysfunction. AB - 1. The haemodynamic effects of adenosine 5'-monophosphate (AMP) and sodium nitroprusside (SNP) were compared in anaesthetized dogs following the induction of acute left ventricular (LV) dysfunction. 2. LV dysfunction was induced by the intracoronary administration of glass microbeads until left ventricular end diastolic pressure (LVEDP) was increased from 5 to 15 mmHg. This was associated with a decrease in LV dP/dt and cardiac index (CI) of 30% and 27%, respectively, and an increase in systemic vascular resistance index (SVRI) of 37%. 3. Graded doses of AMP (100 to 1000 micrograms kg-1 min-1) or SNP (1 to 10 micrograms kg-1 min-1) reduced SVRI and increased CI in a dose-related manner. Heart rate was not altered by either agent. At doses that caused similar reductions in SVRI, CI was increased more by AMP than by SNP. 4. The mechanisms responsible for the greater elevation of CI by AMP relative to SNP may be related to its more selective arterial vasodilator activity. SNP reduced cardiac preload that limited the expected increase in CI. 5. The haemodynamic profile of AMP suggests that it may be useful in the pharmacological management of acute cardiac failure, either when used alone or in combination with positive inotropic agents and/or selective venodilators. PMID- 1933133 TI - Effects of pinacidil on contractile proteins in high K(+)-treated intact, and in beta-escin-treated skinned smooth muscle of the rabbit mesenteric artery. AB - 1. The effects of pinacidil were investigated on changes in cellular Ca2+ concentration ([Ca2+]i) and tension in intact and chemically skinned smooth muscle strips of the rabbit mesenteric artery. 2. High K+ (128 mM) produced a large phasic followed by a tonic increase in [Ca2+]i and tension in intact muscle strips. Pinacidil at 10 microM but not 1 microM, inhibited the phasic and tonic contractions induced by 128 mM K+ without a corresponding change in [Ca2+]i. 3. In beta-escin-treated skinned smooth muscle, the minimum Ca2+ concentration that produced contraction was 0.1 microM and the maximum contraction was obtained at 10 microM. Pinacidil at 10 microM but not 1 microM, shifted the pCa-tension relation curve to the right and also inhibited the maximum contraction induced by Ca2+. The concentrations of Ca2+ required for half maximal tension were 0.9 microM in control and 1.5 microM in the presence of 10 microM pinacidil. Calmodulin (2 microM) increased the contraction induced by 0.3 microM Ca2+ (but not by 10 microM Ca2+) in the skinned strips. Pinacidil (10 microM) inhibited the contraction induced by 0.3 microM or 10 microM Ca2+ in the presence of 2 microM calmodulin. 4. Noradrenaline (NA, 10 microM) with guanosine triphosphate (GTP, 3 microM), guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S, 3 microM) or 12-O tetradecanoylphorbol-13-acetate (TPA, 0.1 microM) all enhanced the contraction induced by 0.3 microM Ca2+. Pinacidil (10 microM) inhibited the contraction induced by 0.3 microM Ca2+ more strongly in the presence of the above agents than in their absence. 5. Following application of 2 mm adenosine-5'-O-(3 thiotriphosphate) (ATPyS) with 0.3 microM Ca2", 4mM MgATP produced contraction in skinned strips in Ca2 -free solution containing 4mM EGTA ('Ca2+- independent contraction'). The amplitude of the Ca2 +-independent contraction was almost the same as that obtained with 1O microM Ca2 . Pinacidil (1O microM) had no effect on the amplitude of the Ca2+-independent contraction nor did it have any effect on the contraction induced by a solution containing no MgATP ('rigor contraction'). 6. It is concluded that pinacidil (10 microM) acts directly on the contractile apparatus to inhibit Ca2'-induced contraction in smooth muscle of the rabbit mesenteric artery. The site of action of pinacidil may be between Ca2 + calmodulin complex formation and phosphorylation of the myosin light chain. PMID- 1933135 TI - The cyclosporin-erythromycin interaction: impaired first pass metabolism in the pig. AB - 1. The pharmacokinetic interaction between cyclosporin (CsA) and erythromycin has been studied in the weanling pig model. 2. Blood CsA and metabolite-1 (M1) concentrations were monitored by high performance liquid chromatography in portal, hepatic and jugular venus blood before and after treatment with erythromycin stearate for 7 days. 3. Erythromycin significantly increased maximum concentration (Cmax) and area under the concentration-time curve from 0 to 24 h (AUC) of CsA in the peripheral circulation. This was accompanied by a significant reduction in the hepatic extraction ratio calculated from portal and hepatic Cmax and AUC data. 4. The extraction ratio appears to be concentration-dependent in that values derived from Cmax (high concentrations) were greater than those from AUC (average concentrations). 5. Time to Cmax (tmax) and t1/2 of CsA were essentially unchanged and no significant changes were observed in peripheral M1 kinetics apart from a small increase in tmax. 6. The pharmacokinetic changes observed in the pig suggest that the CsA-erythromycin interaction is caused by inhibition of hepatic metabolism and the impact of inhibition is greatest during first-pass when CsA concentrations are at their highest. PMID- 1933134 TI - (+)-S-12967 and (-)-S-12968: 1,4-dihydropyridine stereoisomers with calcium channel agonistic and antagonistic properties in rat resistance arteries. AB - 1. The actions of (+)-S-12967 and (-)-S-12968 two isomers of a new 1,4 dihydropyridine (DHP) derivative, were studied on 125 mM K(+)-, Ca(2+)- and noradrenaline-induced contractions in rat isolated mesenteric resistance arteries and compared to those of nifedipine. 2. The action of (+)-S-12967 and (-)-S-12968 was slow in onset in contrast to nifedipine. Both isomers had a dual contractile and relaxant action in arteries contracted with 125 mM K+; however, the (-) isomer was about 300 times more potent than the (+)-isomer. The response to 125 mM K+, being depressed by 70%, recovered within 20 to 30 min for all DHP derivatives. All vessels were treated with 1 x 10(-6) M phenoxybenzamine thus excluding the possibility that the contraction is mediated by activation of amine receptors. 3. Both (+)-S-12967 and (-)-S-12968 at low concentrations potentiated responses induced by Ca2+ in arteries activated by 125 mM K+ and inhibited the responses at higher concentrations. (+)-S-12967 and (-)-S-12968 had no contractile action in arteries kept in normal buffer. Nifedipine had only an inhibitory action on vessel responses to 125 mM K+ and Ca2+. 4. Both isomers and nifedipine depressed the maximal vessel response to noradrenaline by about 20% and 44%, respectively. 5. The results confirm that DHP calcium antagonists selectively inhibit vascular smooth muscle responses induced by high potassium and that the potency of 1,4-DHP isomers may vary considerably. Furthermore, since the agonistic/antagonistic properties on the calcium channel were shared by both stereoisomers of the 1,4-DHP molecule and apparently dependent on their concentration and the vascular smooth muscle membrane potential, it suggests that the agonistic action of 1,4-DHPs may be ascribed to functional characteristics of their binding site regulating the Ca2l -channel. PMID- 1933136 TI - Effects of NG-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, 5'-N-ethylcarboxamidoadenosine or salbutamol in conscious rats. AB - 1. Conscious, Long Evans rats (n = 16), chronically instrumented for the measurement of regional haemodynamics were given 3 min, randomized infusions of two doses of sodium nitroprusside (1.5 and 15 micrograms min-1), acetylcholine (0.4 and 4 micrograms min-1), 5'-N-ethylcarboxamidoadenosine (NECA; 45 and 450 ng min-1), and salbutamol (24 and 240 ng min-1) in the absence and in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 1 mg kg-1 h-1), a potent inhibitor of nitric oxide biosynthesis. 2. Sodium nitroprusside caused hyperaemic vasodilatation in the mesenteric, and common carotid vascular beds. These effects were enhanced in the presence of L-NAME, as was the hypotension. 3. Acetylcholine caused hyperaemic vasodilation inp6he renal, internal carotid and common carotid vascular beds. These effects were attenuated in the presence of L-NAME, but the hypotension was unaffected. 4. NECA caused hyperaemic vasodiltation in the renal, mesenteric, hindquarters, internal carotid and common carotid vascular beds. However, only the hindquarters and internal carotid responses were diminished in the presence of L-NAME and the hypotension was unchanged. 5. Salbutamol caused hyperaemic vasodilatation in the hindquarters vascular bed only. This effect was reduced in the presence of L-NAME, but the hypotension was unchanged. 6. The results indicate marked regional variations in the sensitivity of vasodilator responses to L-NAME that can depend on the vasodilator agent chosen and the dose employed. It is clear from these findings also that measurement of mean arterial blood pressure alone cannot provide adequate information on which to judge the involvement of L-NAME-sensitive mechanisms in vasodilator responses in vivo. PMID- 1933137 TI - On the histamine-induced depolarization of the isolated superior cervical ganglion of the rat. AB - 1. Using a grease-gap technique, we studied the action of histamine on the d.c. potential recorded between the internal carotid nerve and the main body of the isolated superior cervical ganglion of the rat. 2. A small, slow depolarization was evoked by 10-300 microM histamine. This response was not reduced by lowering the calcium concentration in the superfusing medium (from 2.5 to 0.1 mM), or by superfusing tetrodotoxin, N-methylatropine, or propranolol (all at 1 microM). 3. Mepyramine (10 nM) antagonized this depolarization, but cimetidine (10 microM), metiamide (30 microM), burimamide (10 microM) and impromidine (1 microM) did not. Two other agonists also evoked a mepyramine-sensitive slow depolarization. The rank order of potencies was histamine greater than N alpha-methyl-histamine greater than 2-methyl-histamine. 4. At concentrations greater than 1 mM, histamine also evoked a larger, faster depolarization. This response was undiminished by reducing the calcium concentration of the medium to 0.1 mM or by adding 1 microM tetrodotoxin. The rank order of potency for the agonists was N alpha-methyl-histamine greater than histamine approximately 2-methyl-histamine. The histamine-induced fast response was not antagonized by any of the above mentioned antagonists. It was slightly reduced by (+)-tubocurarine (100 microM) and N-methylbicuculline (100 microM) but such effects were not consistent with the blockade of nicotinic or GABAA receptor-mediated responses. 5. It was concluded that histamine depolarized the isolated superior cervical ganglion of the rat by activating H1 receptors. Relatively high concentrations of histamine also evoked a fast depolarization of this preparation, but this did not appear to be mediated by H1, H2 or H3 receptors. PMID- 1933138 TI - Characterization of prejunctional muscarinic autoreceptors in the guinea-pig trachea. AB - 1. The effects of ten muscarinic antagonists on electrically evoked [3H] acetylcholine release and muscle contraction were compared in an epithelium-free preparation of the guinea-pig trachea that had been preincubated with [3H] choline. 2. The M3-selective antagonists UH-AH 37, 4-diphenyl-acetoxy-N piperidine methobromide and para-fluorohexahydrosiladiphenidol were more potent in reducing the contractile response than in facilitating the evoked [3H] acetylcholine release. Hexahydrosiladiphenidol did not discriminate between pre- and postjunctional effects. The rank order of the postjunctional potencies of the ten antagonists as well as the postjunctional pA2 values obtained for hexahydrosiladiphenidol (7.95) and AQ-RA (7.08) identified the muscular receptor as an M3 subtype. 3. The M2-selective antagonists methoctramine, AF-DX 116 and AQ RA 741 were more potent in facilitating the evoked [3H]-acetylcholine release than in inhibiting the contractile response. The increase in release by low concentrations of methoctramine, AF-DX 116 and AQ-RA 741 was paralleled by an enhancement of the stimulation-evoked contractions. 4. Comparison of the pre- and postjunctional potencies of the M1-, M2- and M3-selective antagonists suggests that autoinhibition of acetylcholine release is mediated via an 'M2-like' receptor which differs from the cardiac type M2 receptor in its relatively high affinity for hexahydrosiladiphenidol. PMID- 1933139 TI - Inhibition of reflex responses of neonate rat lumbar spinal cord by 5 hydroxytryptamine. AB - 1. Monosynaptic (MSR) and polysynaptic (PSR) segmental reflex responses were recorded from a ventral root of the neonate rat hemisected spinal cord. Amplitudes of the two components were monitored with a peak height detector. 2. 5 Hydroxytryptamine (5-HT) depressed the MSR and PSR in a concentration-dependent manner. The IC50 for MSR depression was 9.5 +/- 3.2 microM and for PSR depression was 9.0 +/- 4.8 microM. 3. Blockade of neuronal uptake of 5-HT by citalopram (0.1 microM) greatly increased sensitivity to 5-HT. In the presence of citalopram, the IC50 for MSR depression was 30 +/- 18 nM and for PSR depression was 89 +/- 23 nM. 4. 5-HT did not depress the MSR or the PSR by releasing glycine since strychnine (1 microM) did not prevent these actions of 5-HT. 5. 5-Carboxamidotryptamine (5 CT), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), RU 24969, 1-[3 (trifluoromethyl)phenyl]-piperazine (TFMPP) and methysergide were full agonists for depression of the MSR. The IC50 for 5-CT was 3.6 +/- 0.5 nM, for 8-OH-DPAT was 0.4 +/- 0.04 microM, for TFMPP was 0.93 +/- 0.3 microM and for methysergide was 21.8 +/- 3.0 nM. The order of potency was 5-CT greater than methysergide greater than 5-HT greater than 8-OH-DPAT greater than TFMPP. 6. 8-OH-DPAT, RU 24969, TFMPP and methysergide had either no or only a minor action in reducing the PSR. 5-CT caused a 50% depression at the highest concentration tested (30 nM). 7. Neither ketanserin (1 microM) nor spiperone (1 microM) caused appreciable blockade of 5-HT depression of the MSR or 5-HT depression of the PSR. 8. Blockers of neuronal 5-HT uptake (citalopram 0.1 or 1 microM, fluvoxamine 1 microM) usually reduced the MSR and, to a lesser extent, the PSR. Reflex depressions were reversed by ketanserin (1 microM). 9. It was concluded that 5-HT has a potent depressant action on segmental reflexes; depression of the MSR is unrelated to depolarization of motoneurones. Although depression of the MSR was mimicked by 5 HTIA receptor ligands, the action of endogenous 5-HT may be mediated through 5 HT2 receptors. Exogenous 5-HT may act at a mixture of 5-HT receptor subtypes to depress the MSR. PMID- 1933140 TI - The effects of naloxone on the cardiovascular and respiratory effects of centrally administered corticotrophin releasing factor in conscious rabbits. AB - 1. The effects of intracerebroventricular (i.c.v.) and intracisternal (i.c.) administration of corticotrophin releasing factor (CRF) (0.5 nmol kg-1) were examined in conscious rabbits. The effect of opioid receptor antagonism was examined to determine whether the responses to CRF were mediated by endogenous opioid peptides. 2. After i.c.v. CRF there was a rise in mean arterial pressure (MAP), heart rate (HR), plasma noradrenaline and adrenaline, and increased behavioural activity. Respiration rate increased, PaCO2 fell, but PaO2 was unchanged. 3. The pressor and behavioural effects of i.c.v. CRF were unaltered by high doses of intravenous naloxone (9 mumols kg-1 bolus followed by 9 mumols kg-1 min-1 infusion); these effects of CRF were also not prevented by double this dose of naloxone. Naloxone attenuated the CRF-induced tachycardia, blocked the increase in respiration rate and increased the fall in PaCO2. 4. After i.c. CRF (0.5 nmol kg-1) there were similar changes in MAP, HR, plasma catecholamines, respiration and behaviour. 5. These results indicate that in conscious rabbits the pressor effects of i.c.v. CRF are not mediated by endogenous opioid peptides. The finding that the effects of CRF were similar after i.c.v. and i.c. administration suggests that these responses may result from actions on brainstem rather than periventricular sites. PMID- 1933142 TI - Age-dependent changes in cardiovascular responses induced by muscimol infused into the nucleus tractus solitarii and nucleus parabrachialis medialis in rats. AB - 1. The effects of muscimol and bicuculline on mean arterial blood pressure (MAP) and heart rate (HR) were studied after their microinfusion into the nucleus tractus solitarii (NTS) and into the nucleus parabrachialis medialis (NPBmed) in 3 and 24 month old rats. 2. In 3 month old rats a dose of 0.01 microgram of muscimol given into the NTS increased MAP, whereas higher doses (0.05, 0.1 and 0.25 microgram) produced dose-dependent bradycardia with either no change (0.05 and 0.1 microgram) or a decrease (0.25 microgram) in MAP. 3. On the other hand, in 24 month old rats, the same doses of muscimol given into the NTS failed to change MAP, whereas in comparison to 3 month old rats they produced a significantly lesser bradycardia. 4. The cardiovascular changes elicited by infusion of muscimol into the NTS in 3 and 24 month old rats were prevented by prior microinfusion of bicuculline into the same site. 5. Muscimol given into the NPBmed in doses from 0.05 to 0.25 microgram produced, in 3 month old rats dose dependent decreases in MAP and HR which were prevented by prior administration of bicuculline. These effects were significantly reduced in 24 month old rats. 6. The present experiments show that with aging there is impairment of GABA-ergic mechanisms involved in the regulation of cardiovascular activity in the NTS and NPBmed. PMID- 1933141 TI - Cholecystokinin release mediated by 5-HT3 receptors in rat cerebral cortex and nucleus accumbens. AB - 1. The effects of 5-hydroxytryptamine (5-HT) on the release of cholexystokinin like immunoreactivity (CCK-LI) were examined in synaptosomes prepared from rat cerebral cortex and nucleus accumbens and depolarized by superfusion with 15 mM KCl. 2. In both areas 5-HT, tested between 0.1 and 100 nM, increased the calcium dependent, depolarization-evoked CCK-LI release in a concentration-related manner. The concentration-response curves did not differ significantly between the two brain areas (EC50: 0.4 +/- 0.045 nM and 0.48 +/- 0.053 nM, respectively, in cortical and n. accumbens synaptosomes; maximal effect: about 60% at 10 nM 5 HT). 3. The 5-HT1/5-HT2 receptor antagonist methiothepin (300 nM) did not affect the CCK-LI release elicited by 10 nM 5-HT. However, the effects of 10 nM 5-HT were antagonized in a concentration-dependent manner by the 5-HT3 receptor antagonists (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930; 0.1-100 nM; IC50: 3.56 +/- 0.42 nM in the cortex and 3.90 +/- 0.50 nM in the n. accumbens) and ondasetron (IC50: 8.15 +/- 0.73 nM in the cerebral cortex). 5-HT (10 nM) was also strongly antagonized by 100 nM 1 alpha H, 3 alpha 5 alpha H tropan-3-yl-3,5-dichlorobenzoate (MDL 72222) another blocker of the 5-HT3 receptor. Moreover, the 5-HT3 receptor agonist 1-phenylbiguanide (tested in the cerebral cortex between 0.1 and 100 nM) enhanced CCK-LI release in a manner almost identical to that of 5-HT (EC50 = 0.64 +/- 0.071 nM). 4. It is concluded that 5-HT can act as a potent releaser of CCK-LI in rat cerebrocortex and nucleus accumbens through the activation of receptors of the 5-HT3 type situated on the CCK-releasing terminals. This interaction may provide a rationale for the clinical development of both 5-HT3 and CCK receptor antagonists as novel anxiolytic drugs. PMID- 1933144 TI - Obligations of kinship in contemporary Britain: is there normative agreement? AB - This article explores the extent to which there is normative agreement in contemporary Britain about the 'proper thing to do' for relatives. Using quantitative survey data generated using the 'vignette technique', the authors assess how far certain policy and sociological assumptions about appropriate kinship obligations hold up to empirical scrutiny. They argue that there is not a straightforward consensus about a set of normative principles but that it is possible to identify patterns of normative agreement. These vary more in line with the circumstances specified in the vignettes than with the social characteristics of the respondents. There is more evidence of a consensus over procedures - that is what factors people should take into account in working out the proper thing to do for relatives - than over the substance of what should be done. The authors conclude that people do not carry around with them stable sets of values and meanings about obligations to kin, but construct them when they have to out of various materials available. PMID- 1933143 TI - Quinidine-induced inhibition of the fast transient outward K+ current in rat melanotrophs. AB - 1. The effect of quinidine on the fast-activating, fast-inactivating potassium current (IK(f] in acutely dissociated melanotrophs of the adult rat pituitary was examined. Macroscopic currents were measured by use of the whole-cell configuration of the patch clamp technique. 2. Bath application of quinidine caused a dose-dependent reduction of the peak amplitude of IK(f). The Kd for blockade of IK(f) at 0 mV was estimated to be 41 +/- 5.6 microM. 3. Quinidine elicited a dose-dependent increase of the rate of the decay of IK(f) and this effect was enhanced by membrane depolarization. The possibility that this phenomenon reflects an open channel blocking reaction is discussed. 4. Quinidine also caused a 5 mV hyperpolarizing shift of the steady-state inactivation curve and increased the half-time for recovery from inactivation. Quinidine did not affect the onset of inactivation measured at -30 mV. 5. Internal quinidine did not appear substantially to affect either the peak amplitude or kinetics of IK(f). 6. A study of some structural analogues showed that hydroquinidine and quinacrine had effects similar to those of quinidine. The effect of quinacrine on the amplitude and kinetics of IK(f) was also pH-dependent. Cinchonine, which bears a close structural resemblance to quinidine, was much less effective as a blocker of IK(f). PMID- 1933145 TI - The social facts of deviance in school: a study of mundane reason. AB - This paper reports an ethnomethodological study of the use of mundane reason in relation to deviance in schools. Its central theme is that the social facts of deviance in schools are constituted through the assumptions, practices and procedures which comprise mundane reason. The data upon which the study is based consist of transcribed tape recordings of meetings between teachers, psychologists and social workers at which children referred from schools to the Child and Family Guidance Service are discussed. The talk in these meetings is shown to reveal the use of mundane reason with respect to a variety of practical actions. These include categorization, accounting for referral and other actions towards referrals, referral recipiency, reporting referrals, and the formulation of reactions to referrals. Each of these practical actions is considered in turn and its contribution to fact constitution identified. Taken together and viewed consecutively, they can be seen to have a cumulative impact on the social constitution of deviance in schools. PMID- 1933146 TI - Recognition of emotion from facial expression via imitation? Some indirect evidence for an old theory. AB - There is considerable evidence now that recognition of emotion from facial expression occurs far above chance, at least for primary emotions. On the other hand, not much research is available studying the process of emotion recognition. An early theory was proposed by Lipps (1907), postulating that an 'imitation drive' accounts for this process. According to this theory, we tend to imitate a facial expression to which we are exposed, via feedback mechanisms we realize that our own imitated facial expression is associated with an emotion, and then we attribute this emotion to the person confronting us. Using Ekman & Friesen's (1976) Pictures of Facial Affect, a study employing 20 subjects was conducted. During the first part subjects had to judge the emotions expressed in the pictures of facial affect. During this task the subjects were videotaped without their knowledge. About two weeks later the same subjects watched the video recordings of their own expressions during the judgement task and had to judge which emotions they had decoded for the respective slides two weeks previously. Results indicate that decoding of emotions from own facial expression and decoding of the respective emotions from pictures of facial affect correspond to a degree above chance. The results are discussed with respect to the possible impact of imitation on the process of emotion recognition. PMID- 1933148 TI - Intergroup violence and intergroup attributions. AB - Pettigrew's (1979) prediction that relative to in-group behaviour, negative out group behaviour would be attributed to internal characteristics, was tested in the context of Northern Ireland's continued conflict. Catholic and Protestant respondents were presented with newsreel footage depicting scenes of in- and out group violence. One showed a Protestant attack on mourners at a Catholic funeral. The other showed a Catholic attack on a car containing two plain clothes soldiers at a Catholic funeral. Using a free response format, subjects' explanations were classified into internal and external attributions. The results showed strong support for Pettigrew's hypothesis. The implications of these findings with regard to the maintenance of intergroup conflict are discussed. PMID- 1933147 TI - Variables relating to the allocation of pocket money to children: parental reasons and values. AB - This study was concerned with relations among parents' beliefs, values and practices in regard to the allocation of pocket money to their children. Mothers and fathers in 133 Adelaide families provided information about the pocket money allowance they gave to each child in their family and they completed items designed to measure the importance of various possible reasons for their allocations (family concern, independence training, child's needs), as well as items that assessed value dimensions (work ethic, social welfare, compassion). Results showed that social welfare values were associated with family concern reasons, and that individualistic work ethic values were associated with independence training reasons but were antagonistic to reasons concerned with meeting the child's needs. The amount of pocket money provided was positively related to both the age of the child and to the importance of family concern reasons. Parents saw independence training and meeting the child's needs as more important reasons for older children and mothers emphasized children's needs more than fathers. These results were discussed in relation to other research on distributive justice, allocation decisions, pocket money and household tasks. PMID- 1933149 TI - Values and judgements of wage differentials. AB - This study examined the relationship between value priorities as assessed by the Rokeach Value Survey (RVS) and judgements of wage differentials. Students completed the RVS and judged the fairness of the wages for a number of jobs. Judgements of fairness were related to differences in value priorities but the justifications provided did not relate to these value priorities or draw on similar systems. The results are discussed in relation to the question of whether or not values are systematically organized, core cognitive constructs. PMID- 1933150 TI - The current status of lithotripsy. PMID- 1933151 TI - Diagnostic and surgical aspects of renal carcinoma with involvement of the inferior vena cava. AB - Over the past 10 years, 13 patients presented with operable renal carcinoma and tumour extension within the inferior vena cava. This was diagnosed accurately in all but 1 patient, using ultrasound. Radical nephrectomy with removal of tumour within the inferior vena cava was performed in all 13 cases, 2 requiring cardiac bypass. There were no operative deaths and 6 patients remain alive and well with a mean follow-up of 2 years. The presence and level of vena caval extension did not appear to have an adverse affect on prognosis. PMID- 1933152 TI - Renal carcinoma with inferior vena cava malignant thrombosis. AB - During an 11-year period a total of 314 patients underwent surgery for renal carcinoma; 70 had venous extension of the tumour, 31 had extension to the main renal vein and were staged V1 and 39 had involvement of the inferior vena cava and were staged V2. Special attention was paid to the latter group, which was divided into 2 subgroups: V2a for caval extension without ingrowth and V2b for caval extension with infiltration of the caval wall. Thirty-eight patients with caval involvement underwent surgery, with a 13% post-operative mortality rate. Most of the patients with malignant caval ingrowth (V2b) had concomitant lymph node and distant metastases. However, some had negative lymph nodes and no metastases at the time of operation. Perifascial nephrectomy associated with caval tumour removal or lateral subhepatic caval resection for patients staged V2aNOMO significantly increased the survival rate when compared with that of patients with no surgery on the obstructed vena cava. Total resection of the completely obstructed subhepatic vena cava for patients staged V2bNOMO has limited indications but, in selected cases, may prolong survival. This retrospective study supports the reintroduction of indicator V in the TNM staging of renal carcinoma and suggests the splitting of stage V2 into V2a for patients with free-floating caval extension and V2b for caval thrombus with ingrowth and caval wall infiltration. PMID- 1933153 TI - Role of magnetic resonance imaging in blunt renal parenchymal trauma. AB - The accuracy of magnetic resonance imaging (MRI) in the evaluation of blunt renal parenchymal trauma was compared with that of contrast-enhanced computed tomography (CT) and ultrasonography (US) in a prospective study of 12 patients. CT was superior to other methods in identifying and characterising the renal parenchymal lesion, and both CT and US exceeded low field MRI in recognising a perirenal fluid collection. The role of high field MRI in the evaluation of blunt renal trauma requires further study. PMID- 1933154 TI - Lumbar nerve root compression and interstitial cystitis--response to decompressive surgery. AB - An identifiable lumbar nerve root compression appears to cause urological dysfunction consistent with interstitial cystitis. Ten patients (9 females, 1 male) were evaluated for chronic pelvic pain. Cystoscopic and histological appearances were consistent with a diagnosis of interstitial cystitis. Magnetic resonance studies of the lower spine consistently demonstrated a lateral compression of the L5 dorsal nerve root. Decompression of the lateral foramina of L5 resulted in immediate relief of pain in 9 patients, who have been followed up for 6 months without a recurrence. Possible mechanisms involving sympathetic dystrophy of the pelvic plexus are reviewed. PMID- 1933155 TI - Bladder dysfunction due to human T-lymphotrophic virus type I associated myelopathy. AB - Bladder dysfunction is a major complication of human T-lymphotrophic virus type I associated myelopathy (HAM). Four patients (3 females and 1 male, aged between 23 and 44 years), who had suffered from HAM for an average of 6 years complained variously of difficulty in micturition, frequency, bed wetting and/or urge incontinence. They were investigated urodynamically. A significant amount of urine was retained in the bladder of 3 patients. During the storage phase, bladder sensation was well preserved in all 4 patients but severe uninhibited detrusor contractions were observed in 3. At micturition, detrusor contractility was present in 3 and completely lost in 1. Of the 4 patients with HAM, 3 suffered from detrusor hyper-reflexia and 1 from detrusor areflexia. PMID- 1933156 TI - Reliability of the urethral closure pressure profile during stress in the diagnosis of genuine stress incontinence. AB - Urethral pressure profile (UPP) measurements were recorded during stress using the method of Brown and Wickham in 981 patients with lower urinary tract symptoms. This procedure was used to identify patients with genuine stress incontinence (GSI). A clinical stress test in the supine and erect position served to confirm urinary leakage. GSI was diagnosed in 661 patients. (67%), whereas no incontinence was demonstrable in 320 (33%). UPP during stress has a high sensitivity (93.3%) and specificity (82.5%). Compared with other urodynamic investigations, the ease with which it can be performed at the same time as other urodynamic procedures makes a reliable diagnostic adjunct in the assessment of patients with GSI. PMID- 1933157 TI - Colonoscopic control of uretero-enteric anastomoses in internal urinary diversion. AB - Twenty-four patients with internal urinary diversion following total bladder ablation underwent colonoscopic control of the uretero-enteric anastomoses. The techniques performed were: rectal bladder with colostomy according to Mauclaire (11 patients); rectal bladder with abdomino-perineal pull-through according to Heitz-Boyer/Hovelacque (6); ureterosigmoidostomy (7). The uretero-enteric anastomoses were divided into 3 categories according to the colonoscopic appearance: "nipple-like", nearly flat and flat anastomosis. Urographic examinations were carried out in all patients and the results demonstrated that the "nipple-like" anastomosis was the most successful for the preservation of upper urinary tract integrity. PMID- 1933158 TI - Carcinoma in situ as a prognostic factor for G3pT1 bladder tumours. AB - G3pT1 bladder cancer has traditionally been regarded as a superficial tumour with a high risk of progression. We have studied 37 patients with initial G3pT1 bladder tumours treated between January 1981 and December 1985. They were divided into 2 groups according to the association with carcinoma in situ (Cis) at the time of diagnosis. Clinical behaviour was analysed at 5 years. The first group (without Cis) showed progression and recurrence rates similar to those of low grade, low stage bladder tumours. The second group (with Cis) had a similar rate of recurrence but their progression rate was 65%. PMID- 1933159 TI - Calculation of irrigant absorption by measurement of breath alcohol level during transurethral resection of the prostate. AB - If ethanol is added to the irrigant used in transurethral resection of the prostate, absorption of the fluid can be immediately detected by measuring the ethanol concentration in the expired breath. During 90 resections where the irrigant contained 1.5% glycine and 1% ethanol, the breath alcohol level was compared with the amount of irrigant absorbed as determined by volumetric measurement. The results showed that the expired-breath ethanol level depended not only on the volume of irrigant absorbed but also on the rate of ethanol diffusion in the total body water, which increased with the ethanol concentration. By applying a derived mathematical model the absorption could be estimated from the breath alcohol level at any time during surgery, with a median deviation of 19% from the measured value. PMID- 1933160 TI - Single-blind, randomised, parallel group study of the Bard Biocath catheter and a silicone elastomer coated catheter. AB - A group of 69 community patients undergoing long-term urethral catheterisation for urinary incontinence took part in this study; 33 patients with a mean age of 70.03 years (+/- 16.6) received the Dow Corning Silastic catheter (16 F 10-ml balloon) and 36 patients with a mean age of 75.61 years (+/- 12.6) received the Bard Biocath catheter (16 F 10-ml balloon). Over a 16-week period catheters were monitored every 2 weeks and changed as necessary. The Bard Biocath catheter remained in situ for an average of 89.61 days (+/- 35.31) and the Silastic catheter remained in situ for an average of 56.7 days (+/- 38.8); this difference was statistically significant. Used catheters were analysed for encrustation using scanning electron microscopy (SEM). The average time in situ for non encrusted Biocath catheters was 83.7 days and 25.28 days for non-encrusted Silastic catheters. It was found that 70% of patients who received Biocath catheters preferred them to their previous catheters whereas only 30% of patients in the Silastic group preferred the trial catheter. The incidence of bypassing was 28% in the Biocath group and 52.8% in the Silastic group. PMID- 1933161 TI - Gluteal device for penile injection. AB - Locally acting vasodilator drugs have been used in the treatment of male impotence. Self injection, which may be most suitable in these circumstances, often presents difficulties. An implantable device was therefore used to make self injection possible for a wider selection of patients and 37 have now been treated successfully between January 1987 and September 1988. PMID- 1933162 TI - A comparison of aspiration, antazoline sclerotherapy and surgery in the treatment of hydrocele. AB - Of 98 hydroceles (mean volume 125 ml) in a consecutive series of 92 patients, treated initially by aspiration, 14% (mean volume 70 ml) were cured. The 76 recurring hydroceles (mean volume 146 ml) were then randomised to either antazoline sclerotherapy on an out-patient basis or surgery. Cure rates were 89 and 100%, respectively, at follow-up 6 months later. Operated patients were admitted for a mean duration of 2.5 days. The results indicated that aspiration alone was inadequate, and sclerotherapy is advocated as the first choice of treatment for hydrocele. PMID- 1933163 TI - Epididymectomy for post-vasectomy pain: histological review. AB - Fifteen epididymectomies were performed on 10 patients with post-vasectomy pain and 12 specimens were available for histopathological review. The findings were compared with those in 2 groups in which epididymectomy was performed for chronic epididymo-orchitis and epididymal cysts. The results showed that 50% of the post vasectomy group were cured by simple epididymectomy. Pathological findings revealed features of long-standing obstruction and interstitial and perineural fibrosis which may have accounted for the pain. It is important to recognise this late complication of vasectomy and, if surgery is to be performed, to include all of the distal vas and previous vasectomy site in the excision. PMID- 1933164 TI - Fifteen-year experience of carcinoma of the scrotum. AB - Between January 1975 and December 1989, 13 men were treated for carcinoma of the scrotum; 11 lesions were squamous cell and 2 basal cell carcinomas. Eleven patients initially underwent local wide excision and 1 local excision with inguinal node dissection. Two patients died of recurrent disease and 4 from unrelated causes, giving a corrected 5-year survival rate of 62.5%. PMID- 1933165 TI - Thirty-year review of intrascrotal rhabdomyosarcoma. AB - Between 1957 and 1987, 6 cases of intrascrotal rhabdomyosarcoma were found in the pathology records for Northern Ireland. Four of these tumours arose from paratesticular tissue and 2 were confined to the testis. Only 1 patient has died of his disease. Two were lost to follow-up after 21 years and are presumed cured. The remaining 3 remain alive and disease-free between 2 and 3 1/2 years after presentation. PMID- 1933166 TI - First clinical report of a new biodegradable membrane for use in urological surgery. AB - Following preliminary in vitro and in vivo experiments a new collagen Vicryl mesh has been devised. The membrane has been extensively tested in the laboratory and has been found to resist the passage of urine. It holds sutures well and has been shown on an experimental animal to be biodegradable. The membrane has now been applied in human subjects. It has been particularly efficacious in renal surgery and as a means of sealing a bladder after it has been opened. With respect to the ureter the sealing effect is excellent, to the extent of having produced a urinoma. The membrane has been found to be easily applied in vesicovaginal fistulae but difficulties have been experienced in the presence of infection. It is also an ideal membrane for repair of a urethrovaginal fistula--an area where natural tissues are less easily available. This is the first recorded use of this new biodegradable membrane in the human subject. PMID- 1933167 TI - Fluoride metabolism and fluoride content of stones from children with endemic vesical stones. AB - Twenty children with endemic vesical stones showed normal plasma and urinary excretion of fluoride on a mean fluoride intake of 2.5 +/- 0.8 mg/24 h. The mean fluoride content of the stones obtained from these children was 315.6 +/- 264.9 micrograms/g in the nucleus and 229.9 +/- 212.8 micrograms/g in the periphery (this was not statistically significant). Calcium-containing stones had a higher fluoride content than stones containing uric acid and ammonium urate. It was concluded that children with endemic vesical stones have normal fluoride metabolism. Trace quantities of fluoride present equally in the nucleus and peripheral parts of the stones suggest that fluoride does not cause initiation or growth of the nucleus of vesical stones and is adventitiously deposited with calcium salts in these stones. PMID- 1933168 TI - Bilateral testicular secondaries from transitional cell carcinoma of the bladder. PMID- 1933169 TI - Meconium vaginalitis. PMID- 1933170 TI - Stone formation on ureteric stents in children. PMID- 1933171 TI - Bladder calculus causing vesicovaginal fistula in pregnancy. PMID- 1933172 TI - Basal cell carcinoma of the scrotum--a rare clinical entity. PMID- 1933173 TI - Pleural effusion associated with urinary extravasation due to renal colic. PMID- 1933174 TI - Megalourethra. PMID- 1933175 TI - Idiopathic retroperitoneal fibrosis treated with ureterolysis and wrapping with expanded polytetrafluoroethylene vascular graft. PMID- 1933176 TI - Which ureteric stent length? PMID- 1933178 TI - Percutaneous ultrasound-guided injection of sodium morrhuate in the treatment of cystic renal masses. PMID- 1933177 TI - New flexible cystoscopic stent retriever forceps. PMID- 1933179 TI - Use of monofilament nylon for accurately localising a blockage in the vas deferens. PMID- 1933180 TI - Pelvic pouches. PMID- 1933181 TI - Postsplenectomy sepsis and its mortality rate: actual versus perceived risks. AB - A collective critical review of the literature on postsplenectomy sepsis from 1952 to 1987 has been undertaken. The reports cover a cohort of 12,514 patients undergoing splenectomy but of these only 5902 reports were sufficiently detailed to allow a useful analysis. The incidence of infection after splenectomy in children under 16 years old was 4.4 per cent with a mortality rate of 2.2 per cent. The corresponding figures for adults were 0.9 per cent and 0.8 per cent respectively. The present analysis of well documented patients has shown that severe infection after splenectomy for benign disease is very uncommon except in infants (infection rate 15.7 per cent) and children below the age of 5 years (infection rate 10.4 per cent). Many of these reported postsplenectomy infections may have been coincidental. It is also apparent that children contract a different type of infection after splenectomy than adults, predominantly a meningitis which is less frequently fatal. Adults, in contrast, appear to develop a septicaemic type of illness associated with a higher mortality rate. This survey has also shown that children are reported to be more susceptible to pneumococcal sepsis than to infection caused by any other organism. Although the removal of the spleen in otherwise normal people does not appear to be associated with an increased frequency of infection, the presence of a coexistent disorder, notably hepatic disease, can increase the risk substantially. PMID- 1933182 TI - Clinical and functional outcome after restorative proctocolectomy. AB - Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) has been carried out on 88 patients since 1982. Three different pouch designs (J, S and W) were used. Ten pouches had to be removed. Detailed analysis was performed on 61 patients (J = 23, S = 15, W = 23) whose pouches had been functioning for at least 6 months. There was no significant difference in surgical complications before or after ileostomy closure between pouch designs but the hospital stay was greater after construction of an S pouch (P less than 0.05). There were no significant differences in stool frequency, degree of continence or urgency between the three types. Twelve patients with J pouches required antidiarrhoeal medication compared with only one with S and five with W pouches. Only seven patients with S pouches could defaecate spontaneously compared with 22 with W pouches and all patients with J pouches (P less than 0.001). Twenty-five of 29 patients who had preservation of the anal transition zone had perfect continence compared with 23 of 32 with a mucosal proctectomy (P = n.s.). Pouchitis occurred in 13 patients, all of whom had ulcerative colitis. In a subgroup of 23 patients, pouch evacuation was assessed scintigraphically. There was no difference in pouch capacity or total volume evacuated, but spontaneous evacuation was better in J and W pouches compared with S pouches. PMID- 1933183 TI - Necrotizing enterocolitis following operation in the neonatal period. AB - Over a 16-year period, 33 newborn infants developed necrotizing enterocolitis (NEC) following some form of operation (accounting for 19 per cent of all neonates with NEC), including repair of myelomeningocele, intestinal atresia, gastroschisis and congenital diaphragmatic hernia. The neonates with postoperative NEC had a median birth-weight of 3.05 (range 1.0-4.4) kg, and median gestational age of 40 (range 27-41) weeks. Twenty patients were treated non-operatively. The remaining 13 required operation for complications of NEC. Twenty-three patients are alive and have been followed for a median of 66 (range 3-168) months. If a neonate deteriorates following any operation NEC must be included in the differential diagnosis. PMID- 1933184 TI - Fibronectin and collagen gene expression in healing experimental colonic anastomoses. AB - The temporal and spatial expression of fibronectin and type I and III collagen genes were studied 1-14 days after surgery in the healing rat colonic anastomosis using recombinant deoxyribonucleic acid techniques. Messenger ribonucleic acids (mRNAs) coding for fibronectin and type III collagen synthesis increased from the first day after operation and type I collagen synthesis increased from the second day after operation, as demonstrated by Northern hybridizations. Maximal mRNA production for fibronectin and collagens was seen at 2 and 7 days, respectively, after anastomosis. Activation of type I and III collagen genes in the anastomotic area was confined to tissues developing in the anastomotic line, the serosal surface and the submucosal layer. Strong fibronectin expression was observed in the same areas. The results suggest that genetic events leading to collagen synthesis in the anastomotic area start immediately after surgery. Maximal gene expression is not reached until 1 week after surgery. PMID- 1933185 TI - Bleeding pseudocysts and pseudoaneurysms in chronic pancreatitis. AB - Spontaneous haemorrhage associated with chronic pancreatitis in 17 patients was related to a pseudocyst in 15 (88 per cent) patients and to pancreatic lithiasis (one patient) or to infarction-rupture of the spleen (one patient). Bleeding was massive in six patients and intermittent in 11. It resulted from erosion of the gastroduodenal or the splenic artery in four patients. Bleeding into the pancreatic duct occurred in four patients and erosion of the duodenum by a bleeding pseudocyst in five. Haemorrhage was confined to a pseudocyst in six patients and was intraperitoneal in two. Of the 15 patients with bleeding pseudocysts, ten underwent primary pancreatic resection (eight proximal and two distal pancreatectomies) with no mortality but four had early complications. Four of the five patients who underwent transcystic ligation of bleeding vessels and pseudocyst drainage had postoperative complications: one died from sepsis and liver failure and three underwent reoperation for severe postoperative bleeding. Of these, two had proximal pancreatic resection with one death. The third patient had further suture ligation and external drainage. The overall postoperative mortality rate was 12 per cent and following emergency surgery 33 per cent. Favourable results were achieved in two-thirds of patients when the primary operative strategy could be directed towards the control of bleeding and removal of the affected pancreatic segment. Primary pancreatic resection, although technically demanding in the presence of haemorrhage, is recommended whenever possible for the treatment of bleeding pancreatic pseudocysts and pseudoaneurysms associated with chronic pancreatitis. PMID- 1933186 TI - Pulmonary microvasculature in experimental acute haemorrhagic and oedematous pancreatitis. AB - The pulmonary microvasculature was examined in two experimental models of acute pancreatitis by scanning electron microscopy of microvascular corrosion casts. Haemorrhagic pancreatitis was induced in eight male Sprague-Dawley rats using an intraductal injection of 5 per cent sodium taurocholate. Oedematous pancreatitis was induced in seven male Sprague-Dawley rats using an intravenous infusion of supramaximal doses of caerulein (5 micrograms/kg per hour). The pulmonary vessels were cast using a polymer resin and the cast studied by scanning electron microscopy at 3 and 12 h in those with haemorrhagic and at 1 and 4 h in those with oedematous pancreatitis. Vascular abnormalities were present in both models at the initial study time with abruptly terminating vessels being more prominent in the caerulein model. At the later times, however, the abnormalities in the sodium taurocholate model were much more severe, with a substantial loss of vascular density, tortuosity and abrupt terminations of those vessels present. Microvascular abnormalities may be responsible for some of the pulmonary changes seen in oedematous and haemorrhagic pancreatitis. PMID- 1933187 TI - Spontaneous perforation of the bile duct in infants. AB - Spontaneous perforation of the bile duct is a rare but well documented condition of infants. Six infants are described, five presenting within 2 months of birth without apparent antecedent factors and one associated with an 'acquired' type I biliary atresia at 8 months. All infants underwent definitive surgery, which included decompression of the biliary tree with cholecystenterostomy or T tube drainage. There was no morbidity or mortality associated with such surgical intervention. PMID- 1933189 TI - Intestinal plication: an alternative to tapered jejunostomy in functional small bowel obstruction. PMID- 1933188 TI - Surgical restraint in the management of liver trauma. AB - Previous experience in Cambridge in the management of liver trauma has led to the evolution of a protocol for surgical intervention to secure control of haemorrhage from the injured liver. We report 80 cases of liver trauma including 12 who were initially managed non-operatively; three of these subsequently required operation. Of the 80, all but five suffered blunt abdominal trauma. Perihepatic packing was used to manage 29 patients, of whom 21 were initially treated elsewhere before being transferred to Cambridge. Six of these required a hemihepatectomy at subsequent exploration. Of the 39 patients who underwent urgent laparotomy and definitive surgery, 11 (28 per cent) died; only three out of 29 (10 per cent) died after initial packing. Only one death from hepatic complications occurred after packing and subsequent transfer. PMID- 1933190 TI - Graft versus host disease in small bowel transplantation. AB - Quantities of organized lymphoid tissue in small bowel allografts may cause graft versus host disease (GVHD) following transplantation. This study examines the effect of graft mesenteric lymphadenectomy on development of GVHD following small bowel transplantation in rats. GVH reactivity was assessed by measuring the degree of graft cell emigration to the host. In the PVG to DA strain combination, graft mesenteric lymphadenectomy led to a significant reduction in graft cell colonization of host lymphoid tissues from 40-50 per cent to 25-35 per cent. Transplantation from PVG to (PVG x DA)F1 hybrids caused fatal GVHD within 21 days whereas when DA donors were used survival was over 30 days. When mesenteric lymphadenectomy was performed on PVG donors, host survival increased by only 3-4 days. Mesenteric lymphadenectomy in DA donors led to long-term recipient survival with no GVHD. Intensity of GVHD following rat small bowel transplantation is a strain-dependent phenomenon and graft mesenteric lymphadenectomy does not always prevent GVHD. The mucosa may have an important immunological role. PMID- 1933191 TI - c-myc protein product is a marker of DNA synthesis but not of malignancy in human gastrointestinal tissues and tumours. AB - c-myc is a conserved cellular gene. The gene product is a nuclear-bound 62,000 molecular weight phosphoprotein (p62c-myc). Although p62c-myc levels have been measured in colorectal cancers, little is known about the expression of the protein in upper gastrointestinal tumours and tissues. Studies were performed on tumour and mucosal specimens from 87 patients with colorectal cancer, from two with polyposis coli, from six with squamous oesophageal carcinomas and from 18 with gastric carcinomas. The mean p62c-myc content was measured in units of fluorescence in the G1 diploid and G2 diploid peaks of the cell cycle by multiparameter flow cytometry using the 6E10 antibody. The nuclear p62c-myc content increased with DNA synthesis in tumours and mucosa. G2 levels of p62c-myc were higher in glandular mucosa than in adenocarcinomas. No differences in peak nuclear c-myc expression were found in relation to histological grade or to anatomical site of colorectal tumours. There was a broadly inverse relationship between G2 p62c-myc levels in tumours and mucosa and their in vivo 5-bromo-2' deoxyuridine labelling indices. Nuclear p62c-myc levels are cell cycle related but the protein has not been shown to be a marker of increased tissue proliferation or of gastrointestinal malignancy. The reduction of the nuclear p62c-myc content of many adenocarcinoma cells compared with glandular mucosa cells suggests that reduced synthesis or nuclear retention of the normal protein may be a factor in the development of gastrointestinal adenocarcinomas, although the mechanism by which this may occur is not clear. PMID- 1933192 TI - Nutritional status after total and partial gastrectomy with Roux-en-Y reconstruction. AB - Dietary intake and nutritional status were studied in two groups of patients after total gastrectomy (n = 10) and after partial gastrectomy (n = 10). All patients were reconstructed with a Roux-en-Y loop. Investigations were carried out 4-17 years after the operation. Eight patients in the group undergoing total gastrectomy and four patients undergoing partial gastrectomy had gastric carcinoma and were without recurrent disease 5-15 years after the operation. A clinical dietician conducted an anthropometric evaluation. All patients underwent an upper gastrointestinal endoscopy, clinical examination, [14C]triolein breath test and a blood chemistry profile. The median weight loss from operation to investigation was 2.1 kg in the partial gastrectomy group and 6.7 kg in the total gastrectomy group (n.s.). After partial gastrectomy three patients had a subnormal body mass index (n.s.). This was not found in the total gastrectomy group. Energy intake was below that recommended in seven patients in the partial gastrectomy group (three of them had a subnormal body mass index) and in two in the total gastrectomy group (n.s.) [14C]triolein breath testing revealed fat malabsorption in three patients after partial gastrectomy and in five patients after total gastrectomy (n.s.). PMID- 1933193 TI - A more physiological alternative to total fundoplication for the surgical correction of resistant gastro-oesophageal reflux. AB - The incidence of mechanical complications associated with the Nissen fundoplication has prompted evaluation of an anti-reflux procedure designed to be simpler and more physiological, and encompassing a broader view of the many factors involved in the anti-reflux mechanism. Preliminary assessment of the first 100 patients with a mean follow-up of 3.5 years showed symptomatic improvement in 96 per cent and complete relief in 85 per cent. A further 100 patients were studied using formal symptom scoring, endoscopy, manometry and pH monitoring performed before operation and 3 months after operation. Similar clinical results were accompanied by improvement in endoscopic oesophagitis in 95 per cent, complete healing in 74 per cent and restoration of the pH profile to physiological levels in 84 per cent. Troublesome mechanical complications comprised a 2 per cent incidence of dysphagia, but there was no gas bloat or inability to belch or vomit, which may relate to the restoration of lower oesophageal sphincter characteristics close to those of 30 asymptomatic controls. The procedure is simpler to perform than total fundoplication, is well tolerated and is applicable to patients with reflux stricture and impaired oesophageal body motility. The results of this study support the hypotheses that effective reflux control can be achieved without total fundoplication by attention to several factors of known relevance to the anti-reflux mechanism, and that restoration of characteristics of the lower oesophageal sphincter close to physiological levels results in a lower incidence of mechanical complications. PMID- 1933194 TI - Surgery improves defective oesophageal peristalsis in patients with gastro oesophageal reflux. AB - Postoperative manometry was carried out in 12 patients with gastro-oesophageal reflux associated with hypomotility of the oesophageal body. A Nissen fundoplication was carried out in all patients. After a median follow-up of 3.5 years, patients underwent clinical, endoscopic, radiological, manometric and pH metric evaluation. Manometric results revealed an overall improvement in oesophageal motor function with an increase in the amplitude of deglutition waves and a decrease in the percentage of deglutitions without response. Six of the patients (one with complete motor failure) recovered normal peristaltic function. Non-specific oesophageal motor disorders may be secondary to gastro-oesophageal reflux and are reversible in nature. PMID- 1933195 TI - Injection sclerotherapy for bleeding varices: risk factors and complications. AB - Risk factors for complications after injection sclerotherapy were studied in 163 patients undergoing 667 treatments for bleeding oesophageal varices. The overall mortality rate was 7 per cent per injection sclerotherapy session; 16 per cent per acute session and 2.4 per cent per elective session. Acute variceal bleeding was controlled by injection sclerotherapy in 91 per cent of patients. Complications occurred after 16 per cent of injection sclerotherapy sessions. Deaths and complications were significantly associated with poor modified Child's grading (P less than 0.001), the first variceal bleed (P less than 0.001), acute injection sclerotherapy (P less than 0.001) and the use of the rigid oesophagoscope (P less than 0.001). PMID- 1933197 TI - Perineal injuries in children. AB - Over a 12-year period, 463 children under 13 years of age were treated for perineal injuries. The most common cause of injury was a fall astride, but motor vehicle trauma and rape were responsible for most of the severe and multiple injuries. Physical or sexual abuse was evident in 178 (38 per cent) of children, and four sustained injuries from forceful enema. Minor abrasions or first degree tears (88 per cent) and second degree tears (6 per cent) were sutured primarily or allowed to granulate with sepsis rates of 1.2 per cent and 14 per cent respectively. Twenty-nine (6 per cent) children sustained third degree lacerations; one died from secondary pelvic haemorrhage. In the 28 survivors, the outcome of primary (18) or delayed (ten) surgical repair was related to whether or not early defunctioning colostomy had been performed. PMID- 1933196 TI - Penetrating missile injuries in the Gulf war 1991. AB - During the recent Gulf war 63 patients with penetrating missile injuries (including 29 Iraqi prisoners of war) underwent operation in a British Army Field Hospital. Their injuries and initial operative management are reported. Fifty-one casualties (81 per cent) suffered an average of nine wounds (range 1-45) due to fragmentation weapons, and 12 casualties sustained bullet wounds. All wounds were explored following the established principles of war surgery. The extremities were involved in 48 patients (76 per cent). Eight compound long bone fractures were managed with external skeletal fixators applied at the time of initial operation. Laparotomy was performed on seven patients, one of whom died. The average duration of operation was 77 min for shrapnel wounds and 85 min for bullet wounds. PMID- 1933198 TI - Effect of initial biopsy procedure on prognosis in Stage 1 invasive cutaneous malignant melanoma: review of 1086 patients. AB - After treatment for primary clinical Stage 1 invasive cutaneous malignant melanoma, 1086 patients were followed for a minimum of 5 years from initial operation. Patient data were retrieved from the unit's melanoma registry; 96 (8.8 per cent) were treated initially by incisional biopsy, 292 (26.9 per cent) by narrow margin excision biopsy and 698 (64.3 per cent) by wide margin excision. Logistic regression analysis was performed to assess the statistical significance of the association between the various factors. The method of initial biopsy was related to maximal tumour thickness, age, and sex. Incisional biopsy rendered 38 out of 96 (40 per cent) lesions not fully assessable on current histopathological criteria, significantly higher than for the other biopsy techniques (P less than 0.0001). Incisional biopsy did not adversely affect prognosis in terms of local recurrence and mortality. Prognosis was related to tumour thickness, age and sex of the patient, and not to biopsy technique. We recommend that all suspicious lesions should be submitted to excisional rather than incisional biopsy to avoid compromising the histological assessment, given the importance of maximal tumour thickness in determining treatment and prognosis. PMID- 1933199 TI - In situ femoropopliteal bypass: localization of arteriovenous fistulae using intraoperative Doppler ultrasonography. PMID- 1933200 TI - Technique and results of localization biopsy in a breast screening programme. AB - The techniques of ultrasonographic and hookwire localization biopsy of impalpable breast lesions detected by a large breast screening unit during its first year of operation are described. Hookwire localization (HL) was performed using mammography. Ultrasonographic localization (UL) was used for lesions readily detectable by ultrasonography by marking the skin directly over the lesion and calculating its depth below the surface. UL is not appropriate when microcalcification is the sole mammographic abnormality. Localization was required for 150 of the 191 (78.5 per cent) screen-detected lesions. HL was used for 94 (62.7 per cent) and UL for 56 (37.3 per cent). Four lesions were missed by HL, none by UL; 35 per cent of lesions removed by HL and 39 per cent by UL were malignant, giving benign: malignant biopsy ratios of 1.8:1 and 1.5:1 respectively. Only 22 percent of the patients required overnight hospital stay. Localization biopsy plays a major role in the surgery for screen-detected lesions and, where applicable, UL is the technique of choice. PMID- 1933201 TI - Routine examination of the vocal cords before and after thyroid and parathyroid surgery. AB - A prospective study of the value of routine examination of the vocal cords in 239 patients before and after thyroid or parathyroid surgery is presented. From the patient's history and voice the surgeon assessed before and after operation whether vocal cord examination was necessary or not. The surgeon's judgement was compared with the phoniatrician's report. All except one of the documented recurrent laryngeal nerve palsies were suspected by the surgeon. No additional important clinical information was gained by the laryngologist's examinations. Routine vocal cord examination in connection with thyroid and parathyroid surgery is probably not necessary. PMID- 1933202 TI - Prevalence of abdominal aortic aneurysm in Western Australia. AB - The prevalence of abdominal aortic aneurysm (AAA) in Western Australia was studied using health department mortality data. Age-standardized and age-specific mortality rates related to the disease were calculated for the period 1980-88. The mortality rate has risen by 36 per cent for men and 24 per cent for women. Most of this rise was due to an increase in non-hospital and emergency admission hospital deaths. The number of elective and emergency operations has also risen. Despite two decades of elective surgery, the mortality rate for AAA continues to rise. This rise is highly suggestive of an increasing prevalence. This contrasts with the decline in deaths from other manifestations of arteriosclerosis and provides support for a policy of screening for aneurysm. PMID- 1933203 TI - Abdominal aortic aneurysm in 4237 screened patients: prevalence, development and management over 6 years. AB - An ultrasonography screening programme for detecting abdominal aortic aneurysm (AAA) in the community is described in which 7200 men and women aged between 65 and 80 years were contacted by letter. Of these, 4237 were screened; the aorta was visualized in 4122 and 179 AAAs of 3 cm or more in diameter were detected (4.3 per cent). Criteria for surgery are suggested and the results of their application prospectively over 6 years are discussed. Using these criteria, under 10 per cent of patients with ultrasonographically-detected AAA should require surgery for this condition provided ultrasonography follow-up is used. PMID- 1933204 TI - Ruptured aortic aneurysm: a proposed classification. AB - There is a wide variation in reported operative mortality rates for ruptured abdominal aortic aneurysm, ranging from 14 to 70 per cent. Although many factors influence this variation, such as the expertise and facilities available at an individual institution, considerable differences could be due to variations in the pattern of referral and the proportion of cases accepted for operation. In this paper a classification applicable to all patients with ruptured aortic aneurysm is proposed; it has been applied prospectively to 100 consecutive patients with ruptured abdominal aortic aneurysm referred to the Edinburgh Vascular Surgical Unit. The classification illustrates how surgical mortality rates ranging from 29 to 52 per cent may be reported using the same mortality data. Two major benefits may derive from the use of such a standard reporting system. Firstly, it allows management deficiencies to be identified easily and, secondly, it should facilitate comparison of results reported from different centres. PMID- 1933205 TI - Detection and characterization of arterial thromboses using a platelet-specific monoclonal antibody (P256 Fab'). AB - Arteriography does not reliably distinguish between acute and chronic arterial occlusions. Seventeen patients with acute lower limb ischaemia were investigated by arteriography and by imaging with a platelet-specific monoclonal antibody (P256 Fab'); 20 MBq 111In-labelled P256 Fab' was administered intravenously and patients were imaged at intervals of between 20 min and 24 h. Thirteen patients were subsequently treated with intra-arterial thrombolysis. In six the images showed foci of increased uptake of 111In-labelled P256 Fab' and the corresponding arterial segment was recanalized. Patency to 30 days was maintained in four cases. Seven patients had negative scans, only four of whom achieved lysis, and two of these suffered early rethrombosis. The remaining four patients were excluded from thrombolysis by the arteriographic appearances. 111In-labelled P256 Fab' imaging can identify sites of acute arterial thrombosis and may have clinical applications in the management of peripheral vascular disease. Further studies are required to test whether the technique has a role to play in patient selection for thrombolysis. PMID- 1933206 TI - Management of critical upper limb ischaemia long after irradiation injury of the subclavian and axillary arteries. PMID- 1933207 TI - Objective assessment of high ligation without stripping the long saphenous vein. AB - Non-invasive methods of venous assessment were used to assess the procedure of high ligation plus multiple avulsion of varicosities for the treatment of varicose veins in 54 limbs. Duplex scanning before operation confirmed saphenofemoral incompetence and excluded short saphenous incompetence. After operation it revealed that in two limbs the saphenofemoral junction was still patent and incompetent. In the 52 limbs in which the junction had been ligated there was persistent reflux down the long saphenous vein in 24 cases. In only two limbs was this attributable to mid-thigh perforating veins. Photoplethysmography was also performed before and after operation and the venous refilling time measured. Improvement in refilling time produced by application of above knee tourniquets before operation was measured (predicted improvement) and the change in refilling time after operation was also recorded (observed improvement). There was a statistically significant correlation between observed improvement and predicted improvement in refilling times in the limbs with no reflux in the long saphenous vein after operation (Pearson's correlation coefficient, r = 0.6, P less than 0.001). There was no correlation between predicted and observed refilling times in the limbs with persisting reflux in the long saphenous vein after operation. In conclusion, this operation fails to control functionally significant reflux within the long saphenous vein in a high proportion of cases. PMID- 1933208 TI - Non-steroidal anti-inflammatory drugs and complicated diverticular disease: a case-control study. PMID- 1933210 TI - Breast disease: new approaches. PMID- 1933209 TI - Stercoral perforation of the colon. PMID- 1933211 TI - Classification of benign breast disorders. The ANDI classification based on physiological processes within the normal breast. AB - Terminology in benign breast conditions has been confused by multiplicity of terms which do not relate accurately to clinical or histological patterns. Further confusion arises because terminology is not based on sound concepts of pathogenesis. The ANDI classification has been put forward as a nomenclature based on pathogenesis to replace the division of benign breast disorders into 'normal' and 'disease'. It recognizes that a spectrum exists for most conditions which extends from normal, through mild abnormality--'aberrations'--to disease. This classification allows precise definition of an individual patient problem in terms of pathogenesis, histology and clinical implications. It has proved helpful in deciding rational clinical management and in teaching the significance of benign breast disorders. PMID- 1933212 TI - Cystic disease and fibroadenoma of the breast: natural history and relation to breast cancer risk. AB - Approximately 25% of all 'discrete' breast lesions are fibroadenomas or breast cysts and they more commonly cause a breast lump than breast cancer. Despite their frequency, their natural history and relationship to subsequent breast cancer have not been clearly defined, although it would appear that palpable breast cysts, but not fibroadenomas, are associated with some increased risk of breast cancer. The diagnosis of these two entities is now possible by fine needle aspiration and excision of these lesions is only indicated in certain circumstances. PMID- 1933213 TI - Non-lactational inflammation and duct ectasia. AB - Many terms, including duct ectasia, secretory disease, periductal mastitis, plasma cell mastitis, have been used in connection with a variety of clinical conditions associated with nipple discharge, non-puerperal sepsis and nipple retraction. The confused nomenclature reflects the uncertainties regarding the singularity or inter-relationships of the main elements--dilated ducts, periductal inflammation, bacterial infection and nipple retraction. Recent clinical studies combined with new histological and bacteriological information have set the scene for better understanding of the pathogenesis and management of these clinical conditions. PMID- 1933214 TI - Diagnosis by team work: an approach to conservatism. AB - In the Nottingham Breast Clinic 5000 new cases are seen annually; 3000 are sent because the general practitioner believes that he/she has found a lump. It is the diagnosis and management of this common problem that is considered in this chapter. The traditional management of the palpable breast lump included excision to establish accurate diagnosis; indeed up until 20 years ago even simple cysts were excised. Now most surgeons accept that a woman with no residual palpable abnormality after aspiration of blood-free fluid from a cyst requires no further treatment. Most solid breast lumps are benign on histological examination; their routine removal a mistake in judgement. The challenge in the management of a palpable lesion is to correctly diagnose all the cancers without having to remove those which are benign, unless the patient wishes. PMID- 1933215 TI - Genesis and source of breast cancer. AB - Premalignancy and cancer risk as indices of cancer origin have become less confusing. Firstly, we are now aware of the time scale of events leading up to clinical presentation, and secondly the nature of probability, inherent to a biological system influenced by genetics, the environment and hormones, is more widely appreciated. Improved understanding of the early phases of cancer, especially origins and sources, stems from correlation of epidemiological, endocrine and histological information. Such data specifically address the modulating influences on structure and activity of breast epithelial units by factors that are linked to cancer risk. Morphology of the normal breast remains a corner stone on which to build concepts of the cellular events involved in the genesis of cancer. Another line of evidence derives from well defined histological characteristics of pathological processes that have been reliably associated with increased cancer risk. These two aspects of analysis encourage belief that heterogeneity is a characteristic of this disease, which has more than one mode of origin and follows variable courses of aggression. In consequence, the aims behind programmes of breast cancer detection and prevention can become more realistic. PMID- 1933216 TI - Curability of breast cancer. AB - Three concepts of cure are defined--statistical, clinical and personal. The evidence for the curability of female breast cancer according to each of these concepts is examined. It is concluded that the presence of statistically or clinically cured groups of patients is not convincingly demonstrated in past series of treated patients, but that a quarter of such patients have experienced personal cure in that they died from some other cause without overt signs of breast cancer present. The level of personal cure in currently treated series of patients should be higher, mainly due to their more favourable stage distribution. PMID- 1933217 TI - Practical application of determinants of cell behaviour. AB - During the last fifteen years there has been considerable innovation and development of techniques which can be used to study cell biology and behaviour. These include immunocytochemistry, monoclonal antibody technology, molecular biology and biomedical engineering resulting in advanced flow and image cytometric systems. The volume of research results emerging from basic scientists, pathologists and clinicians relative to these techniques is ever increasing. This generation of data demonstrates the immense interest in the potential of these methods to provide useful information of biological and clinical importance. Breast cancer is one area that has received such attention because of its frequency in western countries and its exhibition of a wide spectrum of clinical behaviour. An acceptance that conservation techniques of surgery and radiotherapy are safe alternatives to mastectomy and developments of chemotherapeutic schedules have now provided the patient, surgeon and oncologist with realistic choices of treatment. The question now being asked by many groups is whether this choice can be influenced appropriately by a knowledge of molecular processes which are present, or that have occurred, and which may influence the tumour cell. PMID- 1933218 TI - Adjuvant systemic therapy for operable breast cancer. AB - Adjuvant systemic therapy is now an important and recognized part of the initial management of patients with operable breast cancer. Its value in delaying relapse and prolonging total survival is established for disease of poor prognosis. For premenopausal patients the currently advised treatment is a 6 months course of CMF polychemotherapy and for postmenopausal patients it is daily tamoxifen for 2 5 years. For patients with disease of good prognosis there is a need to evaluate, within randomized trials, the usefulness of newer biological indicators of prognosis to improve selection for and of treatment. Continued monitoring of long term results for delayed morbidity is also necessary. PMID- 1933219 TI - Primary systemic therapy for breast cancer. AB - The use of primary systemic chemotherapy for the treatment of 'operable' breast cancer evolved from the need to improve the outlook of patients with disease that is locally advanced but apparently without metastases. Trials are now showing that this can also be a worthwhile approach to the treatment of primary breast cancer in the elderly. PMID- 1933220 TI - Psychosocial and sexual impact of diagnosis and treatment of breast cancer. AB - Psychosocial and sexual disturbances are common sequelae to a diagnosis of breast cancer and its treatment. The intuitively plausible hope that the advent of breast conserving techniques would prevent the psychological distress experienced following mastectomy has not been realised. Studies comparing psychosocial outcome of mastectomy with lumpectomy and radiotherapy reveal some advantage to women treated with breast conserving procedures in terms of body image, but very little difference in terms of psychiatric morbidity or sexual dysfunction. Whatever the primary therapy, women must still confront the fact that they have had cancer, a life-threatening disease which may recur. In this chapter the research comparing psychological outcome between mastectomy and lumpectomy is critically reviewed and the implications that these data have for clinical practice are discussed. PMID- 1933221 TI - Screening for breast cancer. AB - Randomised trials of screening have clearly demonstrated a substantial reduction of the order of 40% in breast cancer mortality among women aged over 50 years when regularly screened every two to three years by mammography. No other screening modality has been demonstrated to be of benefit, nor has screening of younger women. The major problem of breast screening at present is the need for greater understanding of the heterogenous natural history of the disease. The extent to which earlier diagnosis improves prognosis is poorly understood, but crucial to determining the full potential of screening. PMID- 1933222 TI - Organisation of a national screening programme. AB - Since March 1988 Health Authorities and Health Boards in the United Kingdom have been phasing in the National Health Service Breast Screening Programme (NHSBSP) which implements the recommendations of the Forrest Report. The Report examined the evidence from a number of countries on the value of screening and concluded that, for women aged 50 and over, screening for breast cancer can reduce mortality by up to one-third. The experience gained in setting up the programme has led to a second document in which are detailed 7 requirements considered essential for high quality and ultimate success. PMID- 1933223 TI - Diagnosis of the impalpable lesion. AB - The use of mammography, to aid the diagnosis of patients with symptoms or as a screening test, presents the problem of diagnosing mammographic abnormalities not associated with a palpable lesion. To deal adequately with this, close co operation is required amongst the radiologist, clinician/surgeon and pathologist/cytologist. A significant number of unnecessary biopsies have been carried out when each of the opinions or procedures are performed in isolation and when communication between the different specialties involved is via formal reports as compared to assessment carried out jointly. PMID- 1933224 TI - Changing role of the pathologist. AB - The pathologist's role in diagnosing and managing patients with breast disorders is changing. The introduction of mammographic screening has altered the spectrum of histological changes presenting to histopathologists for diagnosis, with a greater emphasis on 'borderline' lesions, and has increased the need for specimen radiography as part of the gross examination of biopsy specimens. Reporting prognostic features of carcinomas is required as they may give an early indication of the impact of screening and increased cytological services are needed to reduce the need for open biopsy. Together with a recent Government White Paper, screening has also stimulated various quality assurance initiatives in breast pathology. Increased therapeutic options with the associated need to counsel patients demand more comprehensive pathological services--particularly pre-operative cytological diagnosis, reporting of prognostic features and determining the adequacy of excision of carcinomas. Finally, the management of patients with primarily benign biopsies may be influenced by the detection of various neoplastic or pre-neoplastic lesions of microscopic size by the pathologist. PMID- 1933225 TI - Breast self-examination. AB - Breast self-examination (BSE) continues to be widely promoted by Government agencies and medical practitioners in Europe and the United States. Point 10 of the European Code Against Cancer exhorts women to 'examine their breasts regularly'. Breast lumps are common and most women will detect a breast abnormality at some time in their life, irrespective of the promotion of BSE by the medical profession. It should be possible to increase a woman's ability to deal better with this anxiety-provoking situation, and to reduce the number of women presenting with locally advanced disease, by appropriate health education. But this does not mean that BSE should be promoted as a screening test for cancer, with the consequent emphasis on vigilance and early self-referral. The natural course of breast cancer is not completely understood. Although stage at diagnosis is related to survival, and mammographic screening trials suggest that early diagnosis (often before a lump is palpable) can lead to effective treatment which prolongs life, earlier treatment of a palpable lump detected by BSE is not guaranteed to improve survival. PMID- 1933226 TI - Diet and breast cancer. AB - The issue of diet as a cause of breast cancer has been dominated by fat. Some have judged this convincing enough to warrant dietary recommendations aimed at prevention. Others find the evidence so far rather weak. PMID- 1933227 TI - Oestrogens and breast cancer: biological considerations. AB - The biology of oestrogens as applied to the development and progression of breast cancer has been reviewed. Particular consideration has been given to: (i) the sources by which the breast and its tumours may be supplied with oestrogen; (ii) the patterns of endogenous oestrogens within the breast; (iii) the mechanisms by which oestrogens may exert their action; and (iv) the molecular events which follow oestrogen deprivation and which may lead to hormone independence. From a greater understanding of these fundamental processes, novel antioestrogenic measures are being developed which represent more acceptable endocrine treatments for patients with breast cancer and offer the hope of preventative medicine for individuals at high risk of the disease. PMID- 1933228 TI - Oestrogens and breast cancer: exogenous hormones. AB - Oestrogens are administered to women as contraceptive agents and as treatment for menopausal symptoms. This article reviews the epidemiological evidence concerning the risk of breast cancer related to both types of medication. It is generally accepted that long-term; high-dose menopausal oestrogen administration without accompanying progestogen is associated with a moderate increase in breast cancer risk; and that combined oral contraceptives reduce the risk of benign breast disease (as well as ovarian and endometrial cancer). The effect of oral contraceptives on breast cancer risk, however, is less certain. Possible reasons for the lack of agreement between recently conducted case-control studies are discussed, concentrating specifically on the effect of possible latency, being the sum of a prolonged induction plus pre-clinical period, in explaining the discrepancies. PMID- 1933229 TI - Prospects for the chemoprevention of breast cancer. AB - Breast cancer is by far the most common type of cancer in women accounting for 20% of all new cases. It is estimated that 1 in 12 women will develop breast cancer at some time in their life. Each year in the UK, 24,500 women are newly diagnosed with breast cancer and 15,000 women die from it. The incidence rates rise from less than 10 per 100,000 women aged under 30 years to 300 per 100,000 in women aged over 85 years. The seriousness of the problem is emphasized by the fact that for women aged 35-54 years, breast cancer is the commonest single cause of all death. Both the incidence and the mortality have slightly increased in recent years, although mainly in the older age groups. There has been a slight decrease in the mortality rates for women aged 15-44 years over the last 35 years, but in all the older age groups there have been increases. PMID- 1933230 TI - Genetic aspects of breast cancer. AB - Of all the factors contributing to breast cancer risk, a strong family history of the disease is the most powerful. Familial clustering is said to have been noted by the Ancient Romans but formal documentation began in the mid-nineteenth century (reviewed in Ref. 1). The French physician Paul Broca noted that in one family (probably his wife's) over four generations 10 out of 24 women had died from breast cancer while several more individuals, of both sexes, had suffered other malignancies. He concluded that this very large excess of cancers could not reasonably be attributed to chance. At the same time he recognized that occasional familial clusters of relatively common conditions would be expected even in the absence of any genetic predisposition and discounted several published reports of 'hereditary cancers', including some of the families collected by his English contemporary Sir James Paget. PMID- 1933231 TI - Reflex sympathetic dystrophy: the significance of differing plasma catecholamine concentrations in affected and unaffected limbs. AB - In 26 patients with features of reflex sympathetic dystrophy, venous blood was collected from painful and unaffected limbs. Levels of plasma adrenaline, noradrenaline and its intracellular metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG), were measured by combined gas chromatography/mass spectrometry. Plasma DHPG was lower on the painful side. Concentration of plasma noradrenaline was also lower on the painful side in patients with widespread allodynia, and in those with hyperhidrosis in the affected hand or foot. These findings do not support the widely held view that autonomic disturbances in reflex sympathetic dystrophy are due to sympathetic overactivity. Rather, they suggest that sweating and changes in peripheral blood flow result from supersensitivity to sympathetic neurotransmitters. After injury, supersensitivity to noradrenaline may also contribute to spontaneous pain and allodynia by disrupting efferent sympathetic modulation of sensation. This would explain why pain and allodynia are relieved by sympathetic blockade, and why noradrenaline rekindles pain in sympathectomized skin. PMID- 1933232 TI - Maturation of human cerebrum observed in vivo during adolescence. AB - In the present study using magnetic resonance imaging (MRI), age changes in the morphology of the cerebral cortex, greatest in the frontal and parietal convexities, were observed during adolescence. Results suggest that increases in cerebrospinal fluid (CSF) within the sulci of these cortical regions accompany grey matter decreases. Smaller reductions in volume are also observed in subcortical grey matter nuclei. These apparent grey matter volume reductions presumably reflect processes of late brain maturation. The changes may be related to decreasing neural plasticity. PMID- 1933233 TI - Medial vs lateral frontal lobe lesions and differential impairment of central gaze fixation maintenance in man. AB - The ability to maintain central-gaze fixation was studied in 35 patients with unilateral frontal lobe lesions. The stability of central-gaze fixation was tested in 2 oculomotor tasks requiring the suppression of reflexive saccades triggered by the sudden appearance of novel, peripheral visual stimuli. In the first task ('Instructed'), maintenance of gaze fixation was based on verbal instruction, whereas, in the second task ('Non-instructed'), it was based upon a foveating mechanism maintained by sensory stimulation during the performance of a categorization task. Patients with frontal lobe lesions were classified into 3 groups: a ventrolateral (n = 18), a dorsolateral (n = 10) and a medial (n = 7) group. The control group consisted of 20 healthy subjects. In the Non-instructed task, no group differences were found in the rate of reflexive saccades. Thus, lesions of the frontal lobe did not affect reactivity to extraneous stimuli per se. The only exception to this rule was the group of patients with ventrolateral lesions in the left frontal lobe, in which a higher number of reflexive saccades directed to the contralateral hemifield was observed. In the Instructed task, 2 different patterns of deficit in suppression of reflexive saccades were found. First, a bidirectional deficit was noted in the ventrolateral group, which might be attributed to an impairment in either maintaining a selected program of behaviour 'on-line' or suppressing inappropriate alternatives interfering with that program. Second, a unidirectional deficit in voluntary suppression of reflexive saccades triggered from within the contralateral hemifield was observed in the medial group. It is suggested that this type of deficit may reflect malfunctioning of the supplementary motor area--anterior cingulate system involved in the suppression of externally triggered interfering programs. Finally, no significant impairment was found in the dorsolateral group. PMID- 1933234 TI - A case of ocular tilt reaction and torsional nystagmus due to direct stimulation of the midbrain in man. AB - A case is presented of a patient who underwent insertion of a periaqueductal grey electrode for the relief of chronic pain. Shortly after insertion, the patient developed a left-sided ocular tilt reaction (OTR). The electrode tip, initially to the right of the midline, was then withdrawn slightly so that it was now on the left side. Stimulation at this point gave rise to a worsening of the tilt reaction, in addition to bilateral counter-clockwise torsional nystagmus. Computerized tomography and stereotactic coordinates indicated that the tip of the electrode was finally situated in the region of the left interstitial nucleus of Cajal (INC). The production of an OTR by stimulation in this region is similar to the phenomenon previously reported in monkeys and cats. The side of the OTR is consistent with previous evidence, suggesting that the utricular pathways cross between medulla and midbrain. PMID- 1933235 TI - Category-specific naming and comprehension impairment: a double dissociation. AB - We describe 2 neurologically impaired patients with lesions involving primarily the left temporal lobe, whose production and comprehension of words in the semantic category of animals were disproportionately spared in 1 case and disproportionately impaired in the other, in comparison to performance with other common categories. This double dissociation provides neurally based evidence for the view that lexical-semantic information is organized categorically. PMID- 1933236 TI - Cognitive impairment in early, untreated Parkinson's disease and its relationship to motor disability. AB - Current knowledge of cognitive dysfunction in Parkinson's disease (PD) has largely been obtained from studies of chronically treated patients in whom effects of disease chronicity, treatment, depression and dementia are confounding factors. Studies of untreated patients have examined few cognitive domains and relationships between cognition, depression and motor disability have been incompletely explored. Accordingly, we studied 60 consecutive patients with newly diagnosed, untreated, idiopathic PD and 37 matched, healthy control subjects; no subject had clinical dementia or depression. All subjects received tests of specific processes of memory and cognition, including working memory, verbal and non-verbal short- and long-term memory, language, visuospatial capacity, set formation and shifting and sequencing. Patients also received quantitative global clinical measures of severity of dementia, depression and motor disability. The PD group as a whole showed deficits in immediate recall of verbal material, language production and semantic fluency, set-formation, cognitive sequencing and working memory and visuomotor construction. However, this group was unimpaired in immediate memory span, long-term forgetting, naming, comprehension and visual perception. Language deficits and more severe frontal lobe impairments were confined to those PD patients scoring abnormally on a Mini Mental State examination. Motor disability correlated strongly with severity of depression but weakly with cognitive impairment. Cognitive sequencing, set-formation and set shifting deficits tended to associate with depression, but otherwise there was no association between cognition and depression. The results indicate dissociation of cognition and motor control in early PD which suggests that cognitive dysfunction is largely independent of frontostriatal dopamine deficiency underlying motor disability. Some, but not all, of the frontal lobe deficits of chronic disease are detectable in early, untreated PD. The pathogenesis of the cognitive deficits shown here appears to involve extrastriatal dopamine systems or non-dopaminergic pathology. Longitudinal study is necessary to determine whether increasing disease duration exacerbates the early cognitive deficits and affects new cognitive domains, in addition to producing increasing motor disability. PMID- 1933237 TI - Force and fatigue in human type I muscle fibres. A surface EMG study in patients with congenital myopathy and type I fibre predominance. AB - An isometric ischaemic intermittent m.biceps brachii exercise test is performed by 4 patients suffering from congenital myopathies which are characterized by a 100% type I fibre predominance, and by 26 healthy volunteers. Thirty contractions per minute are made at an 80% of maximal voluntary contraction level. It is found that type I muscle fibres have a fourfold lower force-generating capacity than type II muscle fibres. The EMG amplitude shows that more EMG voltage is needed per unit force in the patients with 100% type I fibres compared with controls. Under standardized fatiguing circumstances the power density frequency spectrum shows a weaker shift to lower frequencies in patients with 100% type I muscle fibres compared with controls. The muscle fibre conduction velocity (MFCV) of type I muscle fibres shows no decline during ischaemic exercise indicating an unimpaired muscle membrane excitability. PMID- 1933238 TI - Auditory-visual associations, hemispheric specialization and temporal-frontal interaction in the rhesus monkey. AB - Monkeys (Macaca mulatta) learned preoperatively to associate each of 6 auditory stimuli with 1 of 6 visual stimuli. Ablation of the left prefrontal cortex in a group of 3 monkeys produced a substantial impairment in performance of the task, though performance was still above chance. Ablation of the right prefrontal cortex in a second group of 3 monkeys was without effect. Subsequently the superior temporal gyrus (auditory cortex) was removed in each animal unilaterally in the hemisphere contralateral to the existing prefrontal ablation. Ablation of the left auditory cortex produced a severe impairment, but ablation of the right auditory cortex was without effect. Finally, forebrain commissurotomy in the animals with left prefrontal and right temporal ablation reduced their performance virtually to chance level. These results are consistent with previous findings indicating a left hemisphere specialization for audition in the monkey, and they give strong support to the idea, derived from previous experiments on difficult associative learning in the monkey, that auditory-visual association depends on a convergence of auditory and visual information in the prefrontal cortex. PMID- 1933239 TI - Kinaesthetic acuity of stutterers and non-stutterers for oral and non-oral movements. AB - Six adult stutterers and six normal speakers were instructed to make the smallest possible movements of the jaw, lower lip, tongue and right index finger, both with and without continuous visual feedback. In the non-visual (kinaesthetic) condition, the stutterers showed significantly larger minimal displacements (MDs) than did the non-stutterers for oral but not for finger movements. However, movements made in the presence of visual feedback were consistently smaller for all subjects than those made without, and no differences in MD were found between the stutterers and the non-stutterers when visual feedback was provided. The results suggested the presence of a sensorimotor deficit among at least some adult stutterers that is confined to oral movements. Given the importance of somatic sensory feedback during speech production, these observed orosensory deficiencies among stutterers may provide important insights into causal factors which contribute to the breakdowns in stutterers' speech. PMID- 1933240 TI - Man in motion. Historical and clinical aspects of vestibular function. A review. AB - This is a review of selected aspects of the history of the vestibular system (J. E. Purkyne, E. Mach, A. Crum-Brown) and of our current understanding of vestibular malfunction in clinical vertigo syndromes. Evidence is presented for a preliminary classification of central vestibular brainstem syndromes according to the three major planes of action of the vestibulo-ocular reflex (VOR): (1) disorders of the VOR in the horizontal (yaw) plane (horizontal nystagmus, pseudo 'vestibular neuritis'); (2) disorders of the VOR in the sagittal (pitch) plane (downbeat nystagmus; upbeat nystagmus); (3) disorders of the VOR in the frontal (roll) plane (ocular tilt reaction; lateropulsion). The pathophysiology of peripheral vestibular disorders is discussed: a specific gravity differential between the cupula fluid and the endolymph (buoyancy mechanism) causes vertigo in benign paroxysmal positioning vertigo and positional alcohol nystagmus. Vestibular neuritis is probably a partial unilateral vestibular paralysis due to viral infection of the superior division of the nerve trunk. The common post traumatic vertigo is explained by otolith dysfunction secondary to dislodged otoconia resulting in unequal loads on the macula beds and a tonus imbalance between the two otoliths. PMID- 1933241 TI - Obsessional slowness. Functional studies with positron emission tomography. AB - Patients with Obsessional Slowness (OS) exhibit extreme slowness in the execution of some everyday tasks, such as washing and eating. This may be due to time consuming rituals, checking behaviour and compulsions. On examination some have neurological signs such as a glabellar tap reflex, cogwheel rigidity or abnormal postures. The purpose of this study was to establish a functional explanation for slowness in this patient group. We have studied 6 OS patients using positron emission tomography (PET) with (15)Oxygen to measure regional cerebral oxygen metabolism and [18F]-6-Fluorodopoa (18F-dopa) to assess the integrity of the presynaptic nigrostriatal system. The findings were of focal hypermetabolism in orbital frontal, premotor and midfrontal cortex, whilst dopa uptake into caudate, putamen and medial frontal cortex was normal. The relationship of these findings to the patients' slowness is discussed. PMID- 1933242 TI - The neurology of obsessional slowness. AB - Seventeen of 59 patients admitted to hospital for treatment of Obsessive Compulsive Disorder (OCD) were found to have significant slowness, mainly due to difficulty in initiating goal-directed action and suppressing intrusive and perseverative behaviour. In this subgroup subtle neurological abnormalities were found more frequently than in healthy controls and included loss of motor fluency, hesitancy of initiation of limb movements, speech and gait abnormalities, cogwheel rigidity, complex repetitive movements and tics. Difficulties in cognitive set-shifting and complex spatial-and-shifting abilities were found on neuropsychological testing, but no correlation was found between these disturbances and either the degree of obsessionality or the severity of motor dysfunction. These results suggest that patients with obsessional slowness may have a dysfunction in the frontal-basal-ganglia loop system. PMID- 1933243 TI - Disturbance of movement vision after bilateral posterior brain damage. Further evidence and follow up observations. AB - In 1983 we reported in this Journal a patient who suffered a disturbance of movement vision in a relatively pure form. This uncommon cerebral visual deficit resulted as a consequence of bilateral brain damage affecting the lateral temporo occipital cortex and the underlying white matter. In this paper we present further evidence for the selectivity of the movement vision deficit. Furthermore, follow-up examination did not reveal any significant change which indicates that the disorder appears irreversible. Magnetic Resonance Imaging (MRI) shows bilateral lesions involving the upper (cranial) part of the occipital gyri and the adjacent portion of the middle temporal gyri, with the main focus of damage in the upper (cranial) banks of the anterior occipital sulcus. In addition, cortico-cortical fibre pathways interconnecting occipital, temporal and parietal 'visual' areas are also affected bilaterally. The selectivity of the movement vision deficit and the irreversibility of the disorder strongly support the idea that movement vision is a separate function which is subserved by a visual pathway specialized for the processing of visual motion. PMID- 1933244 TI - Factors affecting visual sensitivity in a hemianopic subject. AB - A well-studied subject with visual cortex damage (G.Y.) was tested in his hemianopic field with temporally modulated sinusoidal and square-wave gratings. The purpose was to use an extended range of parameters to obtain a detailed spatiotemporal specification of his residual vision and to try to resolve the discrepancy between negative findings of Hess and Pointer (1989) and previous positive claims. Both the spatial and temporal parameters could be Gaussian weighted. Detection as a function of spatial frequency, contrast, temporal modulation frequency, stimulus size, and slope of the temporal and spatial Gaussian functions was investigated using a two-alternative forced-choice procedure. The most important parameters for this subject were found to be the slope of the temporal Gaussian function and the size and contrast of gratings. With optimum parameters he could reliably achieve a score of 95-100% correct in his 'blind' field. The results are consistent with earlier studies of this subject, especially his ability to respond to moving stimuli, and also may account for why negative results had been reported for him when particular fixed parameters were used. PMID- 1933245 TI - Ageing and Parkinson's disease: substantia nigra regional selectivity. AB - The micro-architecture of the substantia nigra was studied in control cases of varying age and patients with parkinsonism. A single 7 mu section stained with haematoxylin and eosin was examined at a specific level within the caudal nigra using strict criteria. The pars compacta was divided into a ventral and a dorsal tier, and each tier was further subdivided into 3 regions. In 36 control cases there was a linear fallout of pigmented neurons with advancing age in the pars compacta of the caudal substantia nigra at a rate of 4.7% per decade. Regionally, the lateral ventral tier was relatively spared (2.1% loss per decade) compared with the medial ventral tier (5.4%) and the dorsal tier (6.9%). In 20 Parkinson's disease (PD) cases of varying disease duration there was an exponential loss of pigmented neurons with a 45% loss in the first decade. Regionally, the pattern was opposite to ageing. Loss was greatest in the lateral ventral tier (average loss 91%) followed by the medial ventral tier (71%) and the dorsal tier (56%). The presymptomatic phase of PD from the onset of neuronal loss was estimated to be about 5 yrs. This phase is represented by incidental Lewy body cases: individuals who die without clinical signs of PD or dementia, but who are found to have Lewy bodies at post-mortem. In 7 cases cell loss was confined to the lateral ventral tier (average loss 52%) congruent with the lateral ventral selectivity of symptomatic PD. It was calculated that at the onset of symptoms there was a 68% cell loss in the lateral ventral tier and a 48% loss in the caudal nigra as a whole. The regional selectivity of PD is relatively specific. In 15 cases of striatonigral degeneration the distribution of cell loss was similar, but the loss in the dorsal tier was greater than PD by 21%. In 14 cases of Steele-Richardson-Olszewski syndrome (SRO) there was no predilection for the lateral ventral tier, but a tendency to involve the medial nigra and spare the lateral. These findings suggest that age-related attrition of pigmented nigral cells is not an important factor in the pathogenesis of PD. PMID- 1933246 TI - Myotonic dystrophy. Predictive value of normal results on clinical examination. AB - Myotonic dystrophy (DM) is well known for its highly variable clinical picture, including the age at which symptoms are first detected. In order to assess the proportion of asymptomatic gene carriers at different ages, we have used linked DNA markers to study individuals at 50% genetic risk of DM, in whom neurological examination, slit-lamp examination and electromyography (EMG) had failed to show diagnostic signs. A total of 139 asymptomatic offspring of DM patients were studied. Our analyses identified 11 out of these 139 as probable gene carriers. Our data show that penetrance of the DM gene increases with age. After correction for the possibility of genetic recombination between the DM gene and the DNA markers used, we calculated the residual chance of carrying the DM gene as 8.3% for clinically normal offspring aged between 20 and 39 yrs. We evaluated several factors that might influence this figure. Neither the sex of the propositus nor that of the affected parent modified the risk of carrying the DM gene. Presence of aspecific lens opacities also did not correlate with the risk of having inherited the DM gene. Since a significant proportion of DM gene carriers are not detected by neurological examination, including slit-lamp examination and EMG, these results confirm the need for DNA analysis in asymptomatic offspring of DM patients. PMID- 1933247 TI - Event-related potentials related to recognition memory. Effects of unilateral temporal lobectomy and temporal lobe epilepsy. AB - Event-related potentials (ERPs) were recorded during a continuous recognition memory task for visually presented words, with a 6 item lag between the first and second presentation of each word. The subjects consisted of: (i) a control group of patients with primary generalized epilepsy; (ii) patients who had undergone either a left or a right anterior temporal lobectomy; (iii) unoperated patients with either left or right unilateral temporal lobe epilepsy. In the controls, ERPs to detected 'old' words were reliably more positive-going in the interval 300 to 600 ms post-stimulus than were ERPs to 'new' items. In both left and right lobectomy patients, 'old/new' ERP differences in the same latency range were significantly smaller than in the controls, and did not differ significantly from zero. At midline electrodes, old/new effects in the temporal lobe epilepsy patients were of similar magnitude to those of the controls. In contrast to the control data, the old/new effects in the temporal lobe epilepsy patients were asymmetric, in that they were smaller over the hemisphere ipsilateral to the seizure focus than over the contralateral hemisphere. No relationship was found across subjects between the magnitude of old/new ERP effects and verbal memory performance. In a second task, occasional non-words had to be discriminated against a background of sequentially presented words, some of which were repetitions of the immediately preceding item. ERPs evoked by repeated words were more positive-going than were those to first presentations; this effect was reliable, and of equivalent size, in all patient groups. It is concluded that in the recognition task, old/new ERP effects are dependent on temporal lobe functioning, but that the anterior temporal lobe is not the principal locus of the generators of these effects. The cognitive processes reflected by these effects do not appear to be strongly lateralized to one hemisphere, and neither do they seem to be necessary for normal verbal memory. PMID- 1933248 TI - Intrahemispheric and interhemispheric spread of cerebral cortical myoclonic activity and its relevance to epilepsy. AB - Nine patients with cortical myoclonus (due to various pathologies), in whom movement of one limb induced bilateral limb jerks, were investigated. Three of these patients also had bilateral cortical reflex myoclonus when one limb was subjected to an electrical stimulus. The relative latencies to onset of electromyogram (EMG) activity in various ipsilateral and contralateral muscles in action and reflex jerks were studied. Bilateral reflex and action jerks induced by unilateral electrical stimuli or limb movement were not synchronous. EMG activity was usually recorded in the muscles of the stimulated or moved limb, before being recorded in the homologous muscles of the contralateral limb. It is proposed that this difference in relative latency between homologous muscles represents the interhemispheric delay due to the transcallosal spread of excitation from one sensorimotor cortex to the opposite cerebral cortex. The relative latencies of muscles on the same side of the body reflected not only the differences in efferent delays from the motor cortex via spinal cord and peripheral nerves, but also delays due to the spread of myoclonic activity within the sensorimotor cortex itself. This intrahemispheric spread followed a grossly somatotopic pattern. It is suggested that this spread involves cortico-cortical pathways. The additional delay due to spread of activity from hand to leg area of the sensorimotor cortex was about 10 ms in the first active hemisphere, in both generalized reflex and action jerks. The delays due to somatotopic spread of activity in the opposite later activated hemisphere were shorter. The tendency for spread of excitation through callosal and cortico-cortical pathways is an additional pathophysiological abnormality in some patients with cortical myoclonus, and may be important in the generalization of seizures seen in these patients. PMID- 1933249 TI - Ludwig Mauthner (1840-1894): neuroanatomist and noted ophthalmologist in Fin-de Siecle Vienna. AB - Ludwig Mauthner was only 19 years old when he published his discovery of the colossal fibers in the spinal cord of fishes which now bear his name. Based on Mauthner's works, archival material, and contemporary sources we provide a summary of his life and work as neuroanatomist and ophthalmologist in imperial Austria. In the years 1859-1863 Mauthner published four papers on the structure of the central nervous system in vertebrates. His first report on fishes contains the original description of a 'colossal myelinated nerve fiber' on each side of the central canal, extending through the entire spinal cord. Another, more general, treatise on 'the morphological elements of the nervous system' (published in 1863) summarizes his neurohistological studies of various vertebrates. It includes a classification of nerve cells based on their (histochemical) reaction to carmine. The main findings were soon shown to be artefactual; the paper had a long-range impact, however, because it provoked fruitful controversy among contemporary neuroanatomists. Mauthner published several monographs and numerous articles in ophthalmology, a newly developing branch of medicine that he chose for his later career. After abruptly resigning from a professorship at Innsbruck University, he opened a private practice in Vienna and continued lecturing in his field. He became a noted eye-surgeon, was elected Assistant Director of the Vienna 'Allgemeine Poliklinik', and in 1894 became Professor and Chair of Ophthalmology at the University of Vienna. Mauthner unexpectedly died on the night following the formal announcement of his appointment. PMID- 1933250 TI - Vibration-evoked startle behavior in larval lampreys. AB - Larval lampreys (ammocoetes) exhibit a rapid vibration-evoked startle response involving a bilateral activation of musculature along the length of the body. The resulting movement is variable, contingent on the animal's prestimulus posture: lateral curves along the trunk and tail contract more on the inner side of the curve than on the outer side. Thus, the startle response increases preexisting body curvature. Because ammocoetes are burrowing filter feeders, this startle behavior results in rapid withdrawal of the head into the burrow. A vibratory pulse to the otic capsules in a semi-intact preparation evokes simultaneous action potentials in both primary Mauthner neurons. Vibration also excites several Muller cells. Intracellular stimulation of one primary Mauthner axon (eliciting one action potential) produces bilateral trunk electromyographic potentials that are smaller than those evoked by vibration; simultaneous stimulation of both Mauthner axons (one action potential each) reproduces the vibration-evoked electromyographic amplitudes. The Mauthner cell's sensitivity to vestibular input is centrally modulated during changes in behavioral state. Mauthner action potentials are most easily elicited by vibratory or electrical stimulation of vestibular afferents while an intact animal is at rest; the same stimuli become subthreshold for Mauthner activity while the animal is swimming. A similar depression of Mauthner excitability is observed in semi-intact preparations during arousal. 'Arousal' was defined by the occurrence of tonic, descending spinal cord discharge. Mauthner cells are tonically depolarized during arousal and exhibit an increased membrane conductance; excitatory postsynaptic potentials evoked by vibratory or electrical stimulation of vestibular afferents are greatly attenuated. Modulated sensory transmission to the Mauthner cell may help to prevent inappropriate activation of the startle circuit. PMID- 1933251 TI - Role of the Mauthner cell in sensorimotor integration by the brain stem escape network. AB - The Mauthner neurons have become synonymous with the C start evasive response of fishes. C starts are a two-part movement pattern. First, the fish bends its body so that it has a C-like profile (stage 1) when viewed from above. Second, the fish rapidly accelerates away from its starting position (stage 2). Until recently, it has been possible to determine the contribution of Mauthner cell activity to the expression of this behavior. In this paper we focus on three of our recent papers that address this issue. Our work combines high-speed digital image analysis of the C start with chronic Mauthner cell and electromyographic recordings, lesions of the Mauthner cells, and stimulation of single Mauthner axons in swimming fishes. This work shows that the firing of the Mauthner cell results in a short-latency body contraction that orients the initial stage of the C start away from the direction of the threatening stimulus. The direction of the escape trajectory, however, is more finely tuned to stimulus angle than can be explained by the firing of just the Mauthner cell and its post-synaptic followers. Precise control of trajectory must, therefore, require participation of other neurons. These neurons together with the Mauthner cell form a system that we term the brain stem escape network. We have identified candidate neurons of this network which can now be studied at the single-cell level. Because of both its accessibility for neurophysiological study and its neuroanatomical simplicity, we assert that the brain stem escape network is a useful preparation for understanding fundamental processes of sensorimotor integration in the brain stem. PMID- 1933252 TI - Spinal network of the Mauthner cell. AB - Most swimming vertebrates, particularly fishes and amphibians, avoid predators by producing an escape behavior initiated by a single action potential in one of a pair of cells, the Mauthner cells, located in the hindbrain. The most prominent feature of this behavior is a rapid, forceful bend of body and tail which leads to a characteristic C bend (stage 1) early in the escape. The spinal output of the Mauthner cell is largely responsible for this bend. Each Mauthner cell sends an axon down the length of the spinal cord on the side opposite the soma. When one Mauthner axon fires, it massively excites the ipsilateral musculature by (1) monosynaptic excitation of the large primary motoneurons that innervate the fast white muscle fibers and (2) polysynaptic excitation of motoneurons which is most likely mediated through an identified class of descending interneurons. While motoneurons on the side of the C bend are excited, excitation of those on the opposite side is blocked by inhibition of primary motoneurons and descending interneurons. This inhibition is mediated by commissural interneurons that are electrotonically coupled to the Mauthner axon and cross the spinal cord to monosynaptically inhibit cells on the opposite side. They inhibit not only primary motoneurons and descending interneurons, but also the commissural inhibitory interneurons on the opposite side. The inhibition of contralateral primary motoneurons and descending interneurons prevents motor activity on the side opposite the C bend from opposing that bend, while the inhibition of commissural interneurons prevents them from interfering, via their inhibitory connections, with excitation of motoneurons on the side of the bend. The spinal network responsible for the bend has several similarities with the spinal network for swimming in other anamniotic vertebrates, including lampreys and embryonic frogs. These similarities reveal important, primitive features of axial motor networks among vertebrates. PMID- 1933253 TI - Sex recognition by electric cues in a sound-producing mormyrid fish, Pollimyrus isidori. AB - This paper evaluates the role of electric cues in the sex recognition behavior of an African electric fish, Polimyrus isidori, during courtship behavior observed in the laboratory. I examined the importance of the electric organ discharge (EOD: waveform of the stereotyped electric organ discharge) and the sequence of pulse intervals (SPI: temporal pattern formed by sequences inter-EOD intervals) experimentally by presenting caged fishes, and electric playbacks (models) to male residents. In this species males court females with sounds, and I used this sonic behavior to measure sex recognition. Resident males produced many more grunt sounds when females were introduced onto their territories, compared with caged males, revealing that residents discriminated the sex of the caged fish. Response rates were correlated with characteristic patterns in the SPI of the introduced fish, suggesting that discrimination was based on electric cues. Moreover, I noted several significant sex differences in the SPIs of caged fishes. Residents also discriminated between electric signals from female and male fishes, played to them through electrodes, indicating that electric cues alone were sufficient for sex recognition. An ANOVA was used to ascertain the role of the SPI and the EOD, by analyzing responses to natural female and male models, as well as responses to male EODs combined with female SPIs, and to female EODs combined with male SPIs (hybrid models). I found that discriminating residents used SPI cues alone, with no dependence on the EOD. Taken together with new data showing that females generate a highly regular SPI during natural courtship encounters with singing males, these result show that SPIs are important in sex recognition in P. isidori. PMID- 1933254 TI - Serotoninergic and enkephalinergic cell groups in the reticular formation of the bat ray and two skates. AB - The distribution of cells which were immunohistochemically positive for leu enkephalin (LENK+) or serotonin (5-HT+), two substances widely distributed in the reticular formation, was determined in two species of skates (Raja binoculata and Raja rhina) and a bat ray (Myliobatis californica). The Rajoids are closely related to the Rhinobatoids which contains Platyrhinoidis, an elasmobranch that does not have a nucleus raphe dorsalis. Myliobatis was chosen for an outgroup comparison. Most of the nuclei that were 5-HT+ were also LENK+. The greatest number of labeled cells was in the hypothalamus bordering the third ventricle and in the neurointermediate lobe of the pituitary. The mesencephalon was rich in cells in the ventral tegmental area bordering the red nucleus. In both genera, there were numerous 5-HT+ and LENK+ fusiform cells paralleling the ventral surface of the metencephalon and myelencephalon. These cells were located in several reticular nuclei but were especially prominent in nucleus reticularis (n.r.) pontis oralis, n.r. magnocellularis, and n.r. paragigantocellularis lateralis. The latter nucleus contained fewer LENK+ than 5-HT+ cells. In both genera, 5-HT+ and LENK+ cells were located in raphe pallidus, raphe obscurus, raphe magnus, raphe centralis superior, and raphe linearis. Minor differences in distribution of the remaining 5-HT+ and LENK+ cell groups were found, but these representative elasmobranchs lack a dorsal raphe nucleus which, in mammals, is the largest serotoninergic group. PMID- 1933255 TI - Cross-linguistic research in aphasia: an overview. PMID- 1933256 TI - Aphasia in Turkish: speech production in Broca's and Wernicke's patients. AB - Turkish speech production was studied in 7 Broca's and 10 Wernicke's aphasics. Turkish is an agglutinative language, with few free-standing closed-class morphemes. The speech of Broca's patients was not telegraphic; although nonfluent, noun and verb suffixes were used appropriately. The speech of Wernicke's aphasics was fluent, using a wide range of often inappropriate forms. Both groups used appropriate nominal morphology. Broca's patients used a limited set of verb forms in contextually appropriate fashion. Wernicke's patients used a wide range of verb forms, all morphosyntactically correct, but often semantically anomalous. Both groups retained canonical subject-object-verb word order and controlled various types of pragmatically appropriate word order variation. It is proposed that aphasic speech patterns reflect retrieval problems rather than impairment of a portion of the language system. PMID- 1933257 TI - Inflectional marking in Hungarian aphasics. AB - How do aphasics deal with the rich inflectional marking available in agglutinative languages like Hungarian? For the Hungarian noun alone, aphasics have to deal with over 15 basic case markings and dozens of possible combinations of these basic markings. Using the picture description task of MacWhinney and Bates (1978), this study examined the use of inflectional markings in nine Broca's and five Wernicke's aphasic speakers of Hungarian. The analysis focused on subject, direct object, indirect object, and locative nominal arguments. Compared to normals, both groups had a much higher rate of omission of all argument types. Subject ellipsis was particularly strong, as it is in normal Hungarian. There was a tendency for Broca's to omit the indirect object and for Wernicke's to omit the direct object. Across argument types, Wernicke's had a much higher level of pronoun usage than did Broca's. Broca's also showed a very high level of article omission. Compared to similar data reported by Slobin (this issue) for Turkish, the Hungarian aphasics showed an elevated level of omission of case markings. Addition errors were quite rare, but there were 14 substitutions of one case marking for another. These errors all involved the substitution of some close semantic competitor. There were no errors in the basic rules for vowel harmony or morpheme order. Overall the results paint a picture of a group of individuals whose grammatical abilities are damaged and noisy, but still largely functional. Neither the view of Broca's as agrammatic nor the view of Wernicke's as paragrammatic was strongly supported. PMID- 1933258 TI - The classifier problem in Chinese aphasia. AB - In recent years, research on the relationship between brain organization and language processing has benefited tremendously from cross-linguistic comparisons of language disorders among different types of aphasic patients. Results from these cross-linguistic studies have shown that the same aphasic syndromes often look very different from one language to another, suggesting that language specific knowledge is largely preserved in Broca's and Wernicke's aphasics. In this paper, Chinese aphasic patients were examined with respect to their (in)ability to use classifiers in a noun phrase. The Chinese language, in addition to its lack of verb conjugation and an absence of noun declension, is exceptional in yet another respect: articles, numerals, and other such modifiers cannot directly precede their associated nouns, there has to be an intervening morpheme called a classifier. The appropriate usage of nominal classifiers is considered to be one of the most difficult aspects of Chinese grammar. Our examination of Chinese aphasic patients revealed two essential points. First, Chinese aphasic patients experience difficulty in the production of nominal classifiers, committing a significant number of errors of omission and/or substitution. Second, two different kinds of substitution errors are observed in Broca's and Wernicke's patients, and the detailed analysis of the difference demands a rethinking of the distinction between agrammatism and paragrammatism. The result adds to a growing body of evidence suggesting that grammar is impaired in fluent as well as nonfluent aphasia. PMID- 1933259 TI - Sentence comprehension in aphasia in two clear case-marking languages. AB - Studies of aphasia in Indo-European languages point to a selective vulnerability of morphological case marking in sentence comprehension. However, in case-marking languages such as German and Serbo-Croatian, the use of case marking to express formal grammatical gender diminishes the clarity of grammatical role marking. In Hungarian and Turkish, there are simple and reliable markings for the direct object. These markings are not linked to grammatical gender. Compared to Hungarian, the Turkish accusative marking is somewhat lower in availability, but somewhat higher in detectability. The processing of these cues by aphasics was tested using the design of MacWhinney, Pleh, and Bates (1985. Cognitive Psychology, 17, 178-209). Simple sentences with two nouns and one transitive verb were read to Broca's and Wernicke's aphasics, anomics, and control subjects in both Turkey and Hungary. The main effect of case marking was extremely strong. However, this was not true for all groups. The aphasics used the case cue far less than the normals, with the Hungarian Wernicke's group showing the greatest loss. Word order variations were largely ignored in all groups whenever the case marking cue was present. When case marking was absent, Turkish subjects had a clear SOV interpretation for NNV sentences and Hungarians had a clear SVO interpretation for NVN sentences, in accord with basic patterns in their languages. When there was a contrast between the animacy of the two nouns, subjects choose the animate nouns significantly more often. The effect of animacy was particularly strong in Turkish, in accord with basic facts of Turkish grammar. In Hungarian, VNN sentences without case marking were interpreted as VOS when the first noun was inanimate. In Turkish, VNN sentences without case marking were often interpreted as VSO. In general, the aphasic subjects showed a clear preservation of virtually all aspects of their native languages, albeit in a much noisier form. Despite the high reliability of the case-marking cue, it was damaged more than the word order cue in English subjects. The near-chance processing of the case cue by the Wernicke's aphasics in Hungarian can probably be attributed to the relatively greater difficulty involved in detecting the Hungarian accusative suffix. PMID- 1933260 TI - Selective impairment of grammatical morphology due to induced stress in normal listeners: implications for aphasia. AB - The traditional clinical picture for English nonfluent aphasics has generally presented the deficit as one of total loss of control over grammatical morphology, with some sparing of word order. This is at odds with recent research involving nonfluent aphasic speakers of highly inflected languages, which has shown that agrammatic performance is characterized by morphological substitution rather than omission errors. If the deficit associated with focal brain damage cannot be adequately accounted for in syndrome-specific ways, we may need to look for language-specific processing explanations. One such explanation has to do with language-specific response to global processing difficulty. The current experiment is designed to study the effects of a stress-related limitation on morphological processing. Normal speakers of a language with a relatively rich morphological system (German) are compared with those of a comparatively impoverished system (English) on different forms of a sentence comprehension task. In one form, "clean" stimuli permit full reliance on all available cues to meaning in each language. In another test, a low-level noise mask partially obscured the stimulus sentences. English speakers, who rely almost exclusively on word order cues, were not affected by the noise manipulation. German speakers relied heavily on morphological and semantic information rather than on word order under "clean" conditions. However, under noise Germans made significantly less use of grammatical morphology, with a trend toward compensatory reliance on word order. The results indicate that a global reduction in processing capacity can affect some aspects of language more than others and suggest that such factors must be taken into account in trying to understand specific impairment of morphology in aphasia. PMID- 1933261 TI - Pronoun comprehension in aphasia: a comparison of three languages. AB - The research reported here investigated the effect of phonological and syntactic factors on the processing of pronouns by aphasics. The comprehension of these "closed-class" elements was studied in three different languages: French, Dutch, and German. The cross-linguistic design made it possible to vary phonological status (clitic/nonclitic) and phrasal category (noun phrase/prepositional phrase) as well as grammatical relation (direct/indirect object) while keeping class membership (closed class) and meaning constant. A sentence-picture matching task was given to 20 German-speaking, 16 Dutch-speaking, and 14 French-speaking aphasics, half of each language group being classified as agrammatic Broca's and half as paragrammatic Wernicke's aphasics. The results suggest that Broca's aphasics' limitations in retrieving pronouns, and therefore other closed-class elements, are not a function of either phonological status, phrasal category, or grammatical relation. These subjects' observed high level of performance on pronouns in language comprehension appears due to the kind of semantic and syntactic information they encode. Our findings indicate that a more refined distinction than closed class vs. open class is necessary. PMID- 1933262 TI - A crosslinguistic study of grammaticality judgments in Broca's aphasia. AB - Crosslinguistic studies of sentence comprehension and production in Broca's aphasia have yielded two complementary findings: (1) grammatical morphology appears to be more impaired than word order principles in every language studied, but (2) the degree to which grammatical morphology is retained by aphasic patients depends upon the "strength" or importance of those morphemes in the patient's premorbid language. In an earlier study comparing violations of word order and agreement, we found that English-speaking Broca's aphasics showed greater sensitivity to errors of ordering than to errors of agreement, providing further evidence for the selective vulnerability of morphology. However, because English is a rigid word order language with a relatively weak inflectional system, it could be argued that word order is resilient to brain damage because it is the strongest source of information in this language. The present study compared the performance of English-speaking Broca's aphasics and normal controls with their Italian counterparts in the same grammaticality judgment experiment. Four predictions relating to our previous work were confirmed. (1) Italian aphasics, like their English-speaking counterparts, showed general preservation of grammatical knowledge and (2) they were able to use this knowledge in an "on line" fashion. (3) Within each language, Broca's aphasics showed greater impairment in their ability to recognize errors of morphological selection (i.e., agreement) compared with errors made by moving the same words to an incorrect position downstream. Nevertheless (4), crosslinguistic differences observed in previous studies of comprehension and production were also observed in this grammaticality judgment task: a processing advantage for agreement errors in Italian normals and aphasics, and a processing advantage for ordering errors in English normals and aphasics. PMID- 1933263 TI - Cerebral lateralization in linguistic and nonlinguistic perception: analysis of cognitive styles in the auditory modality. AB - Twenty-two normal subjects (9 left-handers, 13 right-handers) and five dyslexic patients (3 right-handers, and 2 left-handers) were characterized by physiologic hemisphere dominance. The latter was determined by the response of the middle cerebral artery (MCA) blood flow velocity, measured using the transcranial Doppler (TCD) technique, to hypoventilation (hypercapnia). Using bilateral almost simultaneous TCD measurements of mean blood flow velocity in the MCA, lateralization was determined in response to linguistic and nonlinguistic paradigms. In relation to the linguistic paradigm, left-handers, showed lateralization to the physiologic nondominant hemisphere, while right-handers showed lateralization to the physiologic dominant hemisphere; dyslexic patients show trends opposite to those in normals. PMID- 1933264 TI - Mental imagery and dyslexia: a deficit in processing multipart visual objects? AB - Dyslexic and normal control subjects memorized simple line patterns inside a grid and subsequently judged whether an "X" would have fallen on the pattern had it been present in an empty grid. The patterns were letters and novel shapes. The grids were presented to the left visual field, to the right visual field, or in central vision. Dyslexic subjects had difficulty generating images of multipart patterns, but this deficit was limited to letters. The findings suggest that dyslexics may have selective difficulty integrating visual information stored in long-term memory. PMID- 1933265 TI - Selective impairment of thematic role assignment in sentence processing. AB - We report the performance of a brain-damaged subject showing a particularly pure dissociation between impairment in processing thematic roles and spared ability to process the morphological structure of sentences. The thematic role processing impairment was observed in both comprehension and production of active and passive reversible sentences, although it was more severe for the latter sentence type. This pattern of performance poses interesting challenges for current conceptions of the nature of language breakdown in aphasia and for models of normal sentence processing. PMID- 1933266 TI - Auditory neglect after right frontal lobe and right pulvinar thalamic lesions. AB - Auditory unilateral neglect or extinction to simultaneous stimulation is reported in a right-handed male with a lesion in the right frontal lobe and in the right thalamic pulvinar area. The patient was submitted to stereotactic thalamotomy for a post-traumatic intentional ataxia in the left extremities. He was subjected to repeated tests with dichotic listening to consonant-vowel syllables under three different attentional instructions. He was also tested monaurally with the same stimulus materials as used in the dichotic test. The results showed almost complete extinction of the left ear input during dichotic presentations, despite normal hearing when tested with audiometer screening. The left ear extinction effect was independent of instructions to attend to the left or right ear input. However, during monaural presentation, correct left ear reports increased to about 85%. The results are interpreted as showing an auditory attentional neglect caused by the right frontal and pulvinar lesions. PMID- 1933268 TI - In vivo dissociation kinetics of [3H]quinuclidinyl benzilate: relationship to muscarinic receptor concentration and in vitro kinetics. AB - The in vivo washout kinetics of [3H]quinuclidinyl benzilate ([3H]QNB) varies significantly in various structures in the rat brain. The slowest washout rates are from the hippocampus, corpus striatum, and cortex, intermediate rates are exhibited from the thalamus and colliculi, while the fastest washout rate is from the cerebellum. We have also demonstrated a difference in the in vitro dissociation rates (k-1) of [3H]QNB from various structures. The k-1 for the hippocampus, corpus striatum and cortex, is two-fold slower than that observed in the thalamus, colliculi, and cerebellum. The differences in the in vitro dissociation kinetics are not, however, sufficient to explain the differences in the in vivo washout kinetics. We have developed a theoretical formulation which describes conditions under which the washout kinetics are a function of the concentration of receptor in a structure. Furthermore, we present a graphical method in which a plot of the reciprocal of the observed washout rate constant, 1/k(obs), vs receptor concentration is linear. Analysis of the washout kinetics of [3H]QNB from various structures of the CNS of rat were well described by this theory when the differences in in vitro k-1 are included. PMID- 1933269 TI - Nitrous oxide inhibits auditory and visual responses of granule cells in the cerebellum. AB - Much of the laboratory investigation on the auditory and visual areas of the posterior vermis has been carried out under barbiturate anesthesia. It is now known that barbiturates potentiate GABA inhibition by binding directly to the GABA receptor protein. Since GABAergic receptors are present in many cell types of the cerebellar cortex, barbiturate anesthesia is likely to interfere severely with cerebellar physiology. We have examined auditory and visual responses in granule cells in the cerebellum of the cat under nitrous oxide anesthesia. To our surprise, nitrous oxide abolished auditory as well as visual responses in the granule cell layer in the posterior vermis. However, both auditory and visual responses recovered after the cessation of nitrous oxide. PMID- 1933267 TI - Comparison of the antinociceptive and motor effects of intrathecal opioid agonists in the rat. AB - This study compared the antinociceptive and motor effects produced by intrathecal administration of selective mu-, delta-, and kappa-opioid receptor agonists in the rat. Changes in nociceptive threshold were measured using the Randall-Selitto paw-withdrawal test and changes in motor coordination were evaluated using the rotarod treadmill test. Each opioid agonist produced statistically significant, dose-dependent increases in mechanical nociceptive thresholds compared to vehicle controls. In the motor coordination studies, DAMGO and DPDPE, but not U50,488H, produced statistically significant decreases in rotarod performance scores compared to vehicle controls. The results of these studies suggest that motor side-effects produced by opioid agonists need to be considered when interpreting the results of antinociceptive tests that are dependent on a normally functioning motor system. PMID- 1933271 TI - Localization of 5-HT3 receptors in the rat brain using [3H]LY278584. AB - 5-HT3 receptors have been localized in the rat brain using the selective antagonist ligand [3H]LY278584. The binding of this ligand to slide mounted tissue sections was characterized by a Kd value of 1.5 nM and a Bmax value of 110 fmol/mg tissue dry weight. The specific binding was displaced by 5-HT or a number of 5-HT3 antagonist compounds. High densities of 5-HT3 receptors were detected in the nucleus of the solitary tract, dorsal motor nucleus of the vagus and area postrema. Moderate levels of binding were found in the glomerular layer of the olfactory bulb, substantia gelatinosa of the trigeminal nucleus and spinal cord and various nuclei of the amygdala. Low levels of binding were found in the superficial laminae of the cerebral cortex and relatively evenly distributed in the hippocampus. These results indicate that [3H]LY278584 is a useful ligand to study 5-HT3 receptors by quantitative autoradiography. PMID- 1933270 TI - Fluoro-Gold: composition, and mechanism of uptake. AB - Determining the mechanism by which fluorescent retrograde neuronal tracers are taken up requires knowledge of their composition. It has been claimed that Fluoro Gold, a retrogradely transported fluorescent neuronal tracer, is 2-hydroxy-4,4' diamidinostilbene (hydroxystilbamidine), an amidine antibiotic. However, this appears questionable, since the fluorescence spectrograms reported for Fluoro Gold differ markedly from the spectrograms previously reported for purified hydroxystilbamidine. To help clarify the mechanism by which Fluoro-Gold might be taken up, it was decided to examine its composition and determine whether hydroxystilbamidine was its active agent. Fluoro-Gold was found by mass spectrometry to contain a component with a molecular weight of 280 Da (identical to that of hydroxystilbamidine), and fluorescence spectroscopy demonstrated the existence of a substance with a fluorescence spectrum similar to that of purified hydroxystilbamidine. Although a major fluorescent impurity was also observed, chromatographic separation of different fluorescent components of Fluoro-Gold suggested that the fraction resembling hydroxystilbamidine was responsible for its retrograde labeling of cells. It is concluded that hydroxystilbamidine is the active constituent of Fluoro-Gold. Chemically, hydroxystilbamidine is a weak base. In this respect it resembles True blue, DAPI, Granular blue, bis-benzimide, Nuclear yellow, and several other retrogradely transported molecules. It is suggested that these agents cross cell membranes in their uncharged form and are trapped in lysosomes and endosomes by a favorable pH gradient. Thus, the uptake of this type of retrograde tracer may be an example of a well-understood process occurring widely throughout biological systems: the trapping of weak bases in acidic cellular compartments. PMID- 1933272 TI - Lower lumbar branching of caudal medullary expiratory neurons of the cat. AB - Extracellular spike activities of medullary expiratory (E) neurons in the caudal ventral respiratory group were recorded in cats anesthetized with sodium pentobarbital. The majority of E neurons extended their axons in the lower lumbar or the sacral segments and distributed collaterals in L5-L7. These results suggest that E neurons are involved not only in respiratory activities but also in the respiratory modulated motor activities of the lower lumbar segments. PMID- 1933273 TI - Neurofilament phosphorylation in the axonless horizontal cells of rat retina. AB - Axonless horizontal cells in the outer plexiform layer of rat retina were studied with 19 monoclonal antibodies reacting with phosphorylated and non-phosphorylated epitopes of the two high molecular weight neurofilament proteins (NF 150K and NF 200K). With 6 antibodies, immunoreactivity was confined to the nerve fiber layer on the inner surface of the retina. Horizontal cells were not stained. Four antibodies in this group were axon-specific, while the remaining two stained motor and sensory neuron perikarya in rat spinal cord and dorsal root ganglia, respectively. Of the 13 antibodies which stained horizontal cells, 11 reacted with phosphorylated epitopes and failed to decorate motor neuron perikarya in the spinal cord, while in dorsal root ganglia, they stained a subpopulation of sensory neurons. PMID- 1933274 TI - The globus pallidus receives a projection from the parafascicular nucleus in the rat. AB - Study of the afferents of the rat globus pallidus (GP) with Fluoro-gold, a retrograde tracer, revealed retrogradely labeled neurons in the ipsilateral parafascicular nucleus of the thalamus (PF), a previously undescribed afferent of the rat GP. We used the anterograde tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L), to confirm and extend our findings. After injections of PHA-L in the PF, labeled fibers with varicosities and terminal specializations were observed in the ipsilateral GP. The topographical organization of the projection is such that lateral and ventral PF neurons project preferentially to respective parts of the GP, and medial PF neurons project primarily to the ventral GP. There were very few labeled fibers seen in the dorsal or medial GP. The presently described projection from the PF to the GP provides an additional route for the PF to influence basal ganglia circuitry. PMID- 1933275 TI - Leukotrienes in brain: natural occurrence and induced changes. AB - Peptidoleukotrienes (SP-LTs) (both total product and individual LTC4 and LTE4 and LTB4 were measured by radioimmunoassay in cerebrospinal fluid (CSF) collected from the third ventricle of conscious cats. Total SP-LT was expressed as LTE4 after treating samples with crude gamma-glutamyltranspeptidase. Prostaglandin (PG) E2 and thromboxane (TX) B2, the stable metabolite of TXA2, were also assayed in part of the experiments. Under basal conditions, SP-LT and LTC4 were consistently measurable (respectively, 327 +/- 14 and 244 +/- 41 pg/ml), while native LTE4 was below the threshold of the assay (60-280 pg/ml) in most cases. LTB4 was barely detectable (30 +/- 2 pg/ml) or not detectable at all. PGE2 was normally less abundant than TXB2 (31 +/- 4 vs 281 +/- 47 pg/ml). Intracerebroventricular (i.c.v.) administration of arachidonic acid (40 microgram) caused a 4-fold increase in SP-LT levels which was relatively small and transient compared to PGE2 (76-fold) and TXB2 (23-fold), while there was no change in either native LTE4 or LTB4. A similar response was obtained with platelet-activating factor (PAF, 1 microgram i.c.v.), though SP-LT elevation (4 fold) was more persistent. A further rise in SP-LT (9-fold) was noted when PAF administration was preceded by indomethacin (500 microgram i.c.v.), whereas PAF effect was reversed by pretreatment with either the PAF antagonist, BN52021 (1 microgram i.c.v.), or the 5-lipoxygenase inhibitors, U-60,257 (75 micrograms i.c.v.) and L-651,392 (10 mg/kg p.o.). PAF was also effective in causing a 3-fold rise in LTC4. Unlike PAF, pyrogens (endotoxin i.c.v. or i.v.; interleukin-1 i.v.) at doses above threshold for fever had no effect on LT levels in CSF, both in the absence and presence of indomethacin pretreatment. We conclude that SP-LTs are a normal constituent of CSF, LTC4, being the major species. The response to PAF accords with a pathogenetic role of the compounds in inflammatory processes and the reactive changes to injury. No evidence was obtained for the involvement of SP-LTs in the central mechanism of fever. PMID- 1933276 TI - Pertussis toxin potentiates seizures induced by pilocarpine, kainic acid and N methyl-D-aspartate. AB - Previous studies with lithium have shown that it potentiated the in vivo response to cholinomimetics in rats, resulting in seizures at otherwise non-convulsant doses, but did not affect seizure activity induced by a number of chemical convulsants including kainic acid and N-methyl-D-aspartate (NMDA). In vitro experiments have suggested that lithium interferes with receptor-mediated second messenger production, possibly due to an action at G-proteins. The present study tested the hypothesis that selective inhibition of G-proteins by in vivo administration of pertussis toxin would induce effects similar to those of lithium. The results reported here demonstrate that pertussis toxin mimics lithium in potentiating the convulsant response to pilocarpine in rats. The effect of pertussis toxin was dose-dependent and the extent of potentiation was over 13-fold, which was remarkably similar to lithium. The seizures were prevented by pretreatment with atropine, phenobarbital or diazepam. L Phenylisopropyladenosine (L-PIA) and MK-801 also demonstrated anticonvulsant activity, with MK-801 also protecting the rats against the rapid death associated with pertussis toxin/pilocarpine-induced seizures. Thus, seizures were cholinergically initiated and were controlled by the same drugs as were lithium/pilocarpine-induced seizures. The results illustrate that in several respects the response to cholinomimetics is modified in a similar manner by lithium and pertussis toxin. However, pertussis toxin lacks the specificity of lithium as it also potentiated the convulsant effects of kainic acid and NMDA. PMID- 1933277 TI - Glutamate metabotropic and AMPA binding sites are reduced in Alzheimer's disease: an autoradiographic study of the hippocampus. AB - The distribution and levels of glutamate metabotropic binding sites were investigated in the hippocampal region of the human brain using quantitative autoradiography in normal subjects and patients with Alzheimer's disease. The topography of glutamate metabotropic binding sites was contrasted with those for kainate and 2-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) in adjacent sections from the same subjects. The regional distribution of glutamate metabotropic binding and AMPA binding were similar, being most abundant in the subiculum and CA1 region and lower in the CA3 region. The distribution of kainate binding differed from that of metabotropic binding being greatest in the deep layers of the parahippocampal gyrus and CA3 and lower in the subiculum and CA1. There were regionally distinct reductions in these non-N-methyl-D-aspartate (non NMDA) binding sites in patients with Alzheimer's disease. Glutamate metabotropic. AMPA and kainate binding were each markedly reduced in the subiculum and the magnitude of the change correlated with neuronal loss within the subiculum. Glutamate metabotropic binding and AMPA binding were reduced significantly in CA1 in subjects with Alzheimer's disease whereas kainate binding was minimally altered in this region. Kainate and AMPA binding were reduced significantly in the parahippocampal gyrus in Alzheimer's disease while glutamate metabotropic binding was not. In a number of hippocampal areas (e.g. dentate gyrus, CA3), the binding of all ligands was minimally altered in Alzheimer's disease. These differences may reflect the localisation of the three types of glutamate binding sites on neuronal elements which are differentially susceptible to the neurodegenerative process of Alzheimer's disease. PMID- 1933278 TI - Hypercapnia and stimulation of the substantia innominata increase rat frontal cortical blood flow by different cholinergic mechanisms. AB - This study was designed to further investigate in the rat how the cerebrovascular response to excitation of the projections from the substantia innominata (SI) to the frontal cerebral cortex was mediated. Local cortical blood flow (CoBF) (by helium clearance) and tissue gas partial pressures (pO2, pCO2) (indices of energy metabolic activity) were measured in the frontal cortex in unanesthetized adult Fischer rats in response to electrical stimulation of the SI and, for comparison, in hypercapnic conditions. SI stimulation and hypercapnia increased CoBF to a similar extent (+92% and +106%, respectively). Differences between the changes in tissue gas partial pressures under hypercapnia and SI stimulation suggest that different patterns of flow-metabolism coupling prevail in the mechanisms underlying the two cerebrovascular responses. Cortical pCO2 increased under hypercapnia, but decreased during SI stimulation, indicating that a 'vascular' mechanism (i.e. independent of energy metabolism activation) is at least partly responsible for the flow increase in the latter condition. However, cortical pO2 rose more under hypercapnia than during SI stimulation, suggesting that oxygen consumption, and hence energy metabolism, was increased in the latter case. The ability of the acetylcholine esterase inhibitor physostigmine and the muscarinic receptor antagonist scopolamine to modulate the responses was quantified. In both experimental conditions, CoBF changes were potentiated by 0.15 mg/kg/h physostigmine (by factors of about 2). In contrast, 1 mg/kg scopolamine reduced by 65% the frontal CoBF response elicited by SI stimulation but was without effect on the response to hypercapnia. Thus, although a cholinergic mechanism may be implicated in both responses, activation of muscarinic receptors appears to occur when the stimulation originates from the SI but not from the hypercapnia. PMID- 1933279 TI - Motor and electroencephalographic response of refractory experimental status epilepticus in rats to treatment with MK-801, diazepam, or MK-801 plus diazepam. AB - Pharmacologic control of refractory status epilepticus has been little-studied in experimental models. In this experiment, rats in status epilepticus induced by lithium and pilocarpine were treated with MK-801 alone, diazepam alone or MK-801 plus diazepam, with treatment begun at a time when this model of status is refractory to anticonvulsant drugs. EEG samples were digitized before and for two hours after treatment, and the digitized samples subjected to computerized frequency analysis. MK-801 plus diazepam halted all manifestations of status epilepticus. Although neither MK-801 alone nor diazepam alone stopped the ongoing electrographic status epilepticus, both drugs diminished motor seizures and total EEG power. MK-801 treatment prevented the progression of changes in EEG pattern which normally occurs in this model of status epilepticus, while diazepam did not. MK-801, with and without diazepam, allowed the rats to survive the episode of status epilepticus, but rats treated with MK-801 alone required several days to recover completely, while the MK-801 plus diazepam rats appeared normal the next day. MK-801 may be a useful agent for treatment of human refractory status epilepticus, because of its neuroprotective action as well as its ability to potentiate GABAergic drugs. PMID- 1933280 TI - Auditory responses in the posterior vermis of the cat: the buried cerebellar cortex. AB - Although an auditory area has been found over the exposed area of lobules VI-VIII in the posterior cerebellar vermis of the cat, there has been little information on its buried portion. This point should be of some concern, since very little of the brain tissue in lobules VI-VIII of the cerebellar cortex is exposed. We have systematically explored the posterior vermis with long electrode tracks and compared auditory responses recorded from neurons within the granule cell layer in the folial crown with those in the buried cortex. There was a similarity between neural activities recorded from the exposed surface area and those from the buried portion both in the temporal discharge pattern of neurons to sound and in the spatial distribution pattern of auditory responses. PMID- 1933281 TI - In vivo electrochemical evidence that the tricyclic antidepressant femoxetine potentiates the morphine-induced increase in 5-HT metabolism in the medullary dorsal horn of freely moving rats. AB - Acute administration of tricyclic antidepressants (TCAs) is known to potentiate morphine antinociception. At the medullary dorsal horn (MDH) level systemic morphine has been shown to increase serotonin (5-HT) metabolism as measured by in vivo electrochemistry in freely moving rats. Using similar electrochemical detection of 5-hydroxyindole (peak '3') within the MDH, the present study investigated the effect of the specific 5-HT uptake inhibitor femoxetine on peak 3 and the effects of this TCA on changes in 5-HT metabolism induced by morphine. Acutely administered femoxetine (40 mg/kg i.p.) (i) induced a small but significant increase in peak 3 and (ii) strongly potentiated the effect of morphine (10 mg/kg i.p.) on 5-HT metabolism, this potentiation being opiate specific since simultaneous injection of naloxone (1 mg/kg i.p.) abolished the effect of morphine. These findings provide an in vivo neurochemical basis for the potentiation of morphine antinociception by TCAs. They further emphasize the importance of 5-HT bulbospinal descending pathways in morphine antinociception. PMID- 1933282 TI - Inhibition of lateral vestibular nucleus neurons by 5-hydroxytryptamine derived from the dorsal raphe nucleus. AB - Electrophysiological studies were performed to elucidate the effect of 5 hydroxytryptamine (5-HT) originating in the dorsal raphe nucleus (DR) on neuronal activity in the lateral vestibular nucleus (LVN) neurons, using cats anesthetized with alpha-chloralose. LVN neurons were classified into monosynaptic and polysynaptic neurons according to their responses to vestibular nerve stimulation. Conditioning stimuli applied to the DR inhibited orthodromic spikes elicited by vestibular nerve stimulation predominantly in polysynaptic neurons of the LVN. The iontophoretic application of 5-HT also inhibited orthodromic spikes of the LVN neurons. A close correlation was observed between the effects of DR conditioning stimulation and iontophoretically applied 5-HT in the same neurons. These inhibitions with both treatments were antagonized during the application of methysergide, a 5-HT antagonist. In the majority of LVN polysynaptic neurons that responded to antidromic stimulation of the ipsilateral or contralateral abducens nucleus, orthodromic spikes elicited by vestibular nerve stimulation were inhibited by DR conditioning stimulation and the iontophoretic application of 5 HT. In contrast, LVN neurons that responded to antidromic stimulation of the vestibulospinal tract were rarely affected by these treatments. These results indicate that 5-HT derived from the DR inhibits the synaptic transmission of LVN polysynaptic neurons ascending to the abducens nucleus, and suggest that 5-HT derived from the DR is involved in the regulation of the vestibulo-ocular reflex. PMID- 1933283 TI - Temporal profile of the effects of pretreatment with brief cerebral ischemia on the neuronal damage following secondary ischemic insult in the gerbil: cumulative damage and protective effects. AB - We examined the response of the gerbil brain to secondary ischemic insult following pretreatment with brief ischemia at intervals of 5 min, 1 and 6 h, 1, 2, 4, 7 and 14 days. Two minutes of bilateral carotid artery occlusion produced no histopathological brain damage, whereas 3 min of occlusion caused a moderate to severe reduction in the number of hippocampal CA1 pyramidal cells. Two-minute occlusion followed by 3-min occlusion at 5-min, 1- and 6-h intervals resulted in almost complete destruction of CA1 neurons. Additional neuronal damage was observed in the striatum at a 1-h interval and in the thalamus and the neocortex at 1- and 6-h intervals. The neuronal damage was most severe at a 1-h interval. Two-minute ischemia followed by 3-min ischemia at intervals of 1, 2, 4 and 7 days, however, caused a marked protective effect, and the hippocampal CA1 neurons were preserved. The protective effect was not observed at a 14-day interval and following pretreatment with 1-min ischemia. Thus, pretreatment with brief ischemia leads to complex responses of the brain to secondary ischemic insult; cumulative damage at intervals of 1-6 h and protective effects at intervals of 1 7 days. PMID- 1933284 TI - The 21-aminosteroid antioxidant tirilazad mesylate, U-74006F, blocks cortical hypoperfusion following spreading depression. AB - Cortical spreading depression (SD) has been implicated in the pathophysiology of classical migraine headache and cerebral ischemia. A reduction in cerebral blood flow (CBF), mimicking that seen during the aura and headache phase of migraine, is typically observed following SD in the rat. This phenomenon may also play a role in potentiating ischemic brain damage. In the present study, brief cortical exposure to 1 M KCl produced a marked suppression of EEG amplitude which persisted 20 min in the rat. Upon normalization of the EEG, cortical blood flow declined 20-30% and remained low for at least 2 h. Treatment with a 1 mg/kg i.v. dose of the 21-aminosteroid antioxidant tirilazad mesylate (U-74006F), 2 min following KCl application, completely blocked the hypoperfusion while leaving the magnitude and duration of the EEG suppression and mean arterial pressure unchanged. Tirilazad mesylate is a potent inhibitor of oxygen radical-mediated lipid peroxidation both in vitro and in vivo. Thus, based on present results, an oxygen radical hypothesis is proposed to account for the SD-induced cerebral hypoperfusion. PMID- 1933285 TI - Beta-endorphin and methionine-enkephalin levels in discrete brain regions, spinal cord, pituitary gland and plasma of morphine tolerant-dependent and abstinent rats. AB - The effect of morphine tolerance-dependence, protracted and naloxone-precipitated abstinence on the levels of beta-endorphin and methionine-enkephalin in discrete brain regions, spinal cord, pituitary gland and plasma was determined in the male Sprague-Dawley rats. Among the brain regions examined, the levels of beta endorphin in descending order were: hypothalamus, amygdala, midbrain, hippocampus corpus striatum, pons and medulla and cortex. The levels of beta-endorphin in midbrain, hypothalamus, and pituitary of morphine tolerant-dependent rats were decreased significantly. During protracted withdrawal beta-endorphin levels were decreased in amygdala, spinal cord and pituitary. During naloxone-precipitated abstinence beta-endorphin levels were increased in corpus striatum, midbrain and cortex. In addition, in naloxone-precipitated abstinence beta-endorphin levels were decreased in pituitary gland and hippocampus but increased in plasma. The levels of methionine-enkephalin in brain regions in decreasing order were: corpus striatum, pons and medulla, amygdala, hypothalamus, midbrain, hippocampus and cortex. The levels of methionine-enkephalin in pons and medulla, amygdala, hippocampus and pituitary gland were decreased in morphine tolerant-dependent rats. During protracted abstinence from morphine, methionine-enkephalin levels in spinal cord, amygdala, pons and medulla, midbrain, cortex, corpus striatum and pituitary gland were decreased. The levels of methionine-enkephalin in hypothalamus and corpus striatum of naloxone-precipitated abstinent rats were increased but were decreased in amygdala and pituitary gland. These results suggest that during morphine tolerance-dependence and during protracted abstinence beta-endorphin and methionine-enkephalin levels in discrete brain regions and pituitary gland are decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933287 TI - Brain-derived cells contain a specific binding site for Gp120 which is not the CD4 antigen. AB - Infection with the human immunodeficiency virus (HIV-1) often produces a set of neuropsychiatric dysfunctions which have been termed the AIDS dementia complex. This complex appears due to the infection of brain cells by HIV-1. If so, brain cells might be expected to contain a binding site for the same viral envelope glycoprotein that enables HIV-1 to bind to other cells (e.g. CD4+ T-cells), gp120. The present study shows that the cells of the brain-derived U-138MG, U 373MG, SK-N-MC and SK-N-SH cell lines bind gp120 in an inhibitable fashion. Binding of gp120 to these cells is inhibited by the dyes Aurintricarboxylic acid (ATA) and Evans blue (EB), which are known to inhibit specific gp120 and HIV-1 binding, and block HIV-1 infection, in CD4-expressing cells. Binding is not inhibited by Aurin, a dye related to ATA but lacking its anti-HIV effects. As expected, anti-CD4 antibodies are ineffective in blocking gp120 binding to brain derived cells. These results suggest that human brain-derived cells possess a specific binding site for gp120 that is not the CD4 antigen. PMID- 1933286 TI - Localization of basic fibroblast growth factor and its mRNA after CNS injury. AB - Basic fibroblast growth factor (FGF) mRNA is increased 4 h after cortical brain injury. In situ hybridization reveals that the increased mRNA persists for at least 2 weeks and that, in areas adjacent and ipsilateral to the lesion, the expression of basic FGF mRNA is also modified. As an example, at three days distal from the lesion, mRNA can be detected in ependymal cells of the lateral ventricle and in selected cells of the hippocampus and cortex. Endothelial cells also synthesize basic FGF mRNA. The increase in basic FGF mRNA is paralleled by similar changes in the localization of the basic FGF protein. Both the intensity and number of cells which stain for basic FGF are increased when they are compared to staining in either the contralateral side or to comparable areas of unlesioned brains. The pattern of mRNA expression is similar from 4 hours to 14 days. Early in the response (4 h to 3 days) on the border of the lesion, the presence of basic FGF is most obvious within the MAC-1-immunopositive population (macrophages and/or microglia). From 7 days to 2 weeks, there has been extensive hypertrophy of the reactive astrocytes which stain intensely for anti-basic FGF(1 24). We conclude that there is increased basic FGF as a function of injury to the CNS. In view of the observation that it is an early and persistent response, the possibility that it plays multiple functions in the regenerative capacity of the CNS is discussed. PMID- 1933288 TI - Adenosine deaminase reduces hypoxic and hypercapnic dilatation of rat pial arterioles: evidence for mediation by adenosine. AB - Rat pial arteries were observed through a closed cranial window during hypercapnic and hypoxic episodes whilst the cerebral cortex was superfused at 37 degrees C first with artificial cerebrospinal fluid (CSF) and subsequently with adenosine deaminase (ADA, 0.5-2.0 U/ml) in CSF. The results indicate that ADA attenuated hypercapnic and hypoxic dilatatory arteriolar responses by 64% and 56% respectively. Recovery was obtained by superfusing with ADA-free CSF for 1 h. We conclude that adenosine is involved in hypercapnia- and hypoxia-evoked dilation of pial arteries. PMID- 1933289 TI - Sex-related olfactory stimuli induce a selective increase in dopamine release in the nucleus accumbens of male rats. A voltammetric study. AB - Changes in the dopaminergic (DA) transmission in the nucleus accumbens were investigated in male rats exposed to sociosexual olfactory stimuli from different conspecifics: receptive female, non-receptive female and intact male. DAergic transmission was assessed by measurement of extracellular levels of DA and dihydroxyphenylacetic acid (DOPAC). Both compounds were recorded by using differential normal pulse voltammetry (DNPV) with electrochemically pretreated carbon fiber electrodes and numerical analysis of the catechol peak. Exposition to receptive female odors induced a marked and selective increase in DA release compared to control values. Exposition to non-receptive female odors and male odors induced an increase in DA release not significantly different from that following the change of environment. In conclusion, mesencephalic DAergic neurons reaching the nucleus accumbens appear to be involved in the perception of behaviorally significant olfactory cues. PMID- 1933290 TI - Lateralized changes in behavior and striatal dopamine release following unilateral tactile stimulation of the perioral region: a microdialysis study. AB - Intracranial microdialysis was used to measure dopamine (DA) release in the ventrolateral neostriatum of freely moving rats before and after unilateral tactile stimulation was applied to the orofacial region. Several behavioral parameters which have been linked to changes in nigrostriatal DA transmission (scanning, or snout contact with the walls of the observation chamber, turning and locomotion) were measured as well. Orofacial stimulation was followed by an asymmetrical increase in DA release with concentrations of transmitter higher in the neostriatum ipsilateral to the side of stimulation. Asymmetrical scanning behavior was observed during the time period when DA release was asymmetric, with rats favoring use of the side of the face contralateral to increased DA release. Increases in the DA metabolites DOPAC and HVA were found in the striatum ipsilateral to stimulation, but were delayed 40 min following the increase in DA. PMID- 1933291 TI - Postmortem cerebral cortex Gs alpha-subunit levels are elevated in bipolar affective disorder. AB - We examined the relative abundance of G-protein subunits in postmortem brain obtained from 7 patients with bipolar affective disorder (BAD) compared with 7 age- and sex-matched controls. G-protein subunit immunoreactivities were determined in membranes prepared from postmortem prefrontal cortex using SDS-PAGE and immunoblotting with specific polyclonal antisera against selected G-protein subunits: Gsa, Gi(1&2) alpha, Go alpha and G beta(1&2). Of these G-protein subunits, only Gs alpha immunoreactivity was found to be significantly elevated in frontal (+ 34%), and occipital (+ 80%) cortex (P less than 0.05) in BAD compared with control subjects. Smaller increments (+ 22%) in cerebellar Gs alpha immunoreactivity were also found but were not statistically significant. On the basis that increased Gs alpha immunoreactivity may reflect enhanced functional responsiveness of the receptor-effector units to which this coupling protein is integral, the present findings suggest that disturbances in Gs-mediated signal transduction may be involved in the pathophysiology of BAD. PMID- 1933292 TI - Cell migration along glial fibers in dissociated cell culture of the frog optic tectum. AB - Migration of neurons along radial glial fibers is associated with the development of laminated regions in the mammalian brain. We examined cell interactions in dissociated cell cultures of the frog optic tectum, which is well laminated. Using time-lapse photography, we observed active migration of neuron-like cells along strands of radial glia-like cells, which were identified by indirect immunocytochemical staining of the glial fibrillary acidic protein. The migration patterns we observed in our cultures are strikingly similar to those found in mammalian cultures. We hypothesize that this type of neuron-glia interaction is involved in the constitution of laminae in the frog optic tectum. PMID- 1933293 TI - Spatial performance correlates with in vitro potentiation in young and aged Fischer 344 rats. AB - Young adult (2-4 months old) and aged (24-26 months old) Fischer 344 (F344) rats were trained for spatial behavior (locating a hidden escape platform) in a circular water maze. The aged rats showed deficits in both the acquisition and retention of the learned response. Following the behavioral training, hippocampal slices from the rats were prepared. Potentiation of CA1 extracellular, somatic field potentials was studied in vitro following either a short stimulus train (4 pulses) or a longer train (50 pulses). Slices from the aged rats showed less short-term potentiation (124.8 +/- 4.9% baseline, mean +/- S.E.M.) at 1 min following the short train in comparison to slices from the young rats (151.8 +/- 7.5%, P less than 0.05). However, following the longer train, no differences were found between the groups in the degree of either short-term (measured at 1 min after stimulation) or long-term potentiation (measured at 60 min). The amount of potentiation seen at various time points after either train correlated with the behavioral measure of retention. These results indicate that F344 rats exhibit age-related behavioral deficits, and age-related synaptic potentiation deficits in response to short stimulation trains. The correlation between the degree of potentiation (both short-term and long-term) and retention of a behavioral task adds strength to the hypothesis that potentiation mechanisms may underlie memory processes. PMID- 1933294 TI - Interactions of methylmercury with rat primary astrocyte cultures: methylmercury efflux. AB - Methylmercury (MeHg) efflux from rat astrocyte cultures was studied to complement our previous studies on uptake of MeHg in these cells. Exchange with extracellular MeHg was not obligatory for the efflux of [203Hg]MeHg into the extracellular media, because efflux occurred into MeHg-free extracellular media, but stimulation of [203Hg]MeHg net efflux was shown when astrocytes were equilibrated in the presence of 'cold' MeHg and graded concentrations of L cysteine. Net efflux of MeHg was most rapid for the first 5 min, and approximately 20% of preloaded [203Hg]MeHg was lost from the astrocytes by 60 min. Uptake of [203Hg]MeHgCl was maximal by 30 min and did not increase when the loading period was extended up to 4 h. However, the total amount of intracellular 203Hg that was available for net efflux gradually decreased as the duration of the preloading period increased. MeHg net efflux from astrocytes was unchanged when [203Hg]MeHgCl preloaded astrocytes were equilibrated in hypotonic buffer, suggesting that unlike ions and amino acids swollen astrocytes remain impervious to MeHg efflux. Thus, the main MeHg efflux transport system is apparently specific for the MeHg-L-cysteine conjugate and represents transport by the same neutral amino acid System L that facilitates its uptake. PMID- 1933295 TI - Single neurone studies of opioid tolerance and dependence at the ventrobasal thalamic level in an experimental model of clinical pain, the arthritic rat. AB - The aim of this electrophysiological study was to investigate the effects of an acute injection of morphine (1 mg/kg i.v.) or the opioid antagonist naloxone (0.6 2 mg/kg i.v.) on thalamic ventrobasal (VB) neuronal activities recorded in arthritic rats rendered tolerant/dependent by pretreatment with relatively low doses of morphine. Recordings were performed in animals immobilized by i.v. injections of gallamine triethiodide (Flaxedil) and artificially ventilated under a moderate gaseous anesthesia (mixture of one-third O2, two-thirds N2O, 0.5-0.6% halothane). This level of anesthesia, as checked by the electrocorticogram, was stable and appeared sufficiently deep, since no sign of suffering or stress could be detected. The efficacy of morphine on VB neuronal responses induced by mild stimulation of the joints was greatly reduced in morphine-pretreated arthritic rats, compared to naive animals (mean neuronal inhibition of 35 vs 85%, respectively). This indicates that the tolerance phenomena observed in behavioral studies are reflected at the VB level, on neurons involved in pain processes. In addition, naloxone (0.6, 1 and 2 mg/kg i.v.) induced a dramatic increase in the evoked (52, 88 and 93%) and spontaneous (64, 211 and 292%) VB neuronal activities recorded in morphine-pretreated arthritic rats, while these activities were not significantly altered in naive arthritic rats. The time-courses of the modifications induced by naloxone in morphine-pretreated arthritic animals were similar to those of the naloxone-precipitated morphine withdrawal observed in freely moving rats. These findings may represent the neuronal correlate at the VB level of the withdrawal response and/or the hyperalgesia induced in tolerant arthritic rats by high doses of naloxone. PMID- 1933296 TI - CRF microinjected into the dorsal vagal complex inhibits TRH analog- and kainic acid-stimulated gastric contractility in rats. AB - The effect of CRF microinjected into the dorsal vagal complex (DVC) on centrally stimulated gastric contractility was investigated in fasted, urethane anesthetized rats. Miniature strain gauge force transducers were acutely implanted on the corpus of the stomach and contractility was analyzed by computer. Microinjection of the stable thyrotropin-releasing hormone (TRH) analog, RX 77368, (26 pmol) into the DVC induced a 12.2-fold stimulation of gastric contractility within 30 min. Corticotropin-releasing factor (CRF) (63-210 pmol) microinjected into the DVC concomitantly with RX 77368 (26 pmol) induced a dose-related inhibition of stimulated gastric contractility. Neither CRF alone (210 pmol) nor vehicle modified basal gastric contractility. Microinjection of kainic acid (141 pmol) into the raphe pallidus nucleus induced a 3.6-fold stimulation of gastric contractility after 45 min. This stimulation was suppressed by bilateral microinjection of CRF (105 pmol/site) into the DVC. These results demonstrate that CRF acts in the DVC to inhibit centrally-stimulated gastric contractility and suggest that TRH and CRF may interact in the DVC to regulate gastric motor function. PMID- 1933297 TI - Dissociation of experimentally induced drinking behavior by ibotenate injection into the median preoptic nucleus. AB - Adult male Sprague-Dawley rats were injected with either ibotenic acid (5 micrograms/1 microliter) or vehicle in the ventral median preoptic nucleus. The injections were given during either methoxyflurane or ketamine anesthesia. None of the rats injected with ibotenic acid were adipsic after surgery. After at least one week of recovery, all rats were tested for drinking responses to angiotensin II (1.5 and 3 mg/kg s.c.) and hypertonic saline (3% and 12% 1 ml/100 g b.wt.). Rats injected with ibotenic acid during methoxyflurane anesthesia drank significantly less than the vehicle injected control group in tests with both doses of angiotensin II and both concentrations of hypertonic saline. The rats that were injected with ibotenic acid during ketamine anesthesia drank significantly less than the control group when tested with 3% hypertonic saline but not when tested with angiotensin II. Histological examination of the injection sites indicated significant reductions in the volume of the median preoptic nucleus only in rats that had been injected with ibotenic acid during methoxyflurane anesthesia. The results are consistent with the interpretation that the drinking response to angiotensin II is dependent upon the integrity of neurons with postsynaptic N-methyl-D-aspartate receptors within the median preoptic nucleus. PMID- 1933298 TI - Sleep alterations in experimental street rabies virus infection occur in the absence of major EEG abnormalities. AB - Brain electrical activity and sleep organization were investigated in chronically implanted mice during street rabies virus infection. Continuous EEG recordings showed no gross electrical abnormalities until a few hours before the fatal issue. In contrast, alterations of sleep stages were observed at an early stage during the course of rabies virus infection, at a time when clinical signs were absent. Quantification by spectral analysis showed that the main feature was the early decrease of REM-sleep stages and the increase of the duration of waking stages. Neuromuscular disorders which could occur early were also observed during the disease. Comparison of these data with those obtained from fixed rabies virus infection shows that in the latter the EEG recordings demonstrated early alterations and a progressive deterioration with disappearance of both sleep and waking stages, which were replaced by a pathological sleep stage. In order to evaluate the potential role of the host-specific immune response in promoting brain electrophysiological alterations, EEG recordings and spectral analysis were also performed in cyclophosphamide-treated mice. Street rabies virus-infected and immunosuppressed mice showed identical physiopathological changes as those observed in immunocompetent mice. The implication of these viral-induced electrophysiological alterations in the context of the pathogenic mechanisms of rabies virus is discussed. PMID- 1933299 TI - Characterization of Vicia villosa agglutinin-labeled GABAergic interneurons in the hippocampal formation and in acutely dissociated hippocampus. AB - The distribution, morphology, and ionic conductances of Vicia villosa agglutinin (VVA)-labeled cells were examined in the rat hippocampal formation. The heaviest labeling and highest density of labeled neurons were found in the subicular complex. Lighter VVA-labeling and fewer labeled cells were found in hippocampal strata pyramidale, oriens, and alveus. VVA-labeled cells were found to be heterogeneous morphologically, including multipolar, bipolar, and basket-like shapes. The majority of VVA-labeled cells contained GABA and parvalbumin immunoreactivity; thus VVA-labeled cells in the hippocampal formation resemble previously described VVA-labeled neurons in cerebral cortex. Electrophysiological properties of subicular VVA-labeled cells were studied in an acutely dissociated neuron preparation. Dissociated cells were labeled in vitro with VVA coupled either to a fluorescent marker or to small beads. The viability of labeled dissociated cells was confirmed, and identified cells were partially characterized electrophysiologically using whole-cell voltage clamp recording. VVA-labeled cells were electrophysiologically similar to pyramidal cells from the same region, except that the VVA-labeled cells showed only small transient outward currents. PMID- 1933300 TI - Kinetic analysis of L-carnitine uptake by the choroid plexus. AB - Choroid plexuses from the lateral (LVCP) and fourth ventricles (FVCP) of rats or rabbits were incubated in artificial cerebrospinal fluid (CSF) containing 1 microM [14C]L-carnitine with various concentrations of L-carnitine ranging from 0.01 mM to 1.0 mM. The time course of 1 microM [14C]L-carnitine uptake by the choroid plexus indicated that it increased linearly for the first 15 min. Steady state levels were reached by 30 min with tissue concentrations more than 20 (FVCP)- to 30 (LVCP)-fold greater than the concentration in the medium. The uptake of [14C]L-carnitine was increased with increasing concentrations of the substrate in the medium and this uptake followed Michaelis-Menten kinetics. The uptake by the rat choroid plexus took place against a concentration gradient via a saturable process and kinetic analysis revealed Km of 32 microM (LVCP) and 34 microM (FVCP) and Vmax of 21 (LVCP) and 17 nmol/ml/min (FVCP), respectively. Ouabain inhibited the uptake by 51% (FVCP) and 48% (LVCP) and hypothermia (0 degrees C) produced inhibition by 97% (FVCP) and 96% (LVCP), respectively. However, the uptake of L-carnitine was not sensitive to probenecid or tyrosine, which indicates the presence of an independent carrier for L-carnitine in the choroid plexus. Similar results were obtained with the rabbit choroid plexus. PMID- 1933301 TI - Effects of thyrotropin-releasing hormone and a related analog, CNK-602A, on long term potentiation in the mossy fiber-CA3 pathway of guinea pig hippocampal slices. AB - The effects of thyrotropin-releasing hormone (TRH) and a related analog, CNK 602A, that induces the release of catecholamines, on long-term potentiation (LTP) of the population spike in mossy fiber-CA3 pathways were investigated in guinea pig hippocampal slices. TRH augmented LTP of the population spike at concentrations of 10(-6)-10(-5) M. CNK-602A also augmented LTP at concentrations of 10(-6)-10(-5) M in a dose-dependent manner. LTP in slices of the hippocampus obtained from animals given 6-hydroxydopamine (6-OHDA) intraventricularly was significantly lower than that in non-treated animals. However, both TRH and CNK 602A (10(-6) M) augmented LTP in slices from 6-OHDA-treated animals. These findings suggest that TRH and CNK-602A augment LTP in the mossy fiber-CA3 pathway without activating noradrenergic and/or dopaminergic fibers. PMID- 1933302 TI - Acute stress induces time-dependent responses in dopamine mesolimbic system. AB - Exposure to either restraint or footshock (3-60 min) induced similar biphasic alterations of 3-methoxytyramine (3-MT) concentrations (initial increase followed by decrease below control levels) in the nucleus accumbens septi (NAS) of mice, as revealed by tissue analysis. The only difference between the two stressors was the earlier onset of the decrease phase in the restrained mice. In both stressful conditions acid metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased throughout stress, while no significant changes in dopamine (DA) concentrations occurred. These data suggest biphasic alteration of DA release during prolonged stress exposure. The analysis of release in restrained conscious rats by in vivo microdialysis (10-240 min) showed a similar biphasic DA evolution (initial increase followed by decrease below baseline levels) in the NAS. The only difference from the previous experiment was the delayed onset of the decrease phase. Similar changes in DOPAC and HVA were also evident. Moreover, freed rats showed an immediate increase of DA release over baseline levels, also indicating that depletion of the neurotransmitter cannot account for the reduction of released DA. Taken together, these results support the hypothesis that biphasic alteration of DA transmission in the mesolimbic system is a general response to stress and suggest that the initial increase of DA release represents an arousal response while the subsequent decrease in DA release may be related to coping failure. PMID- 1933303 TI - MCD peptide and dendrotoxin I activate c-fos and c-jun expression by acting on two different types of K+ channels. A discrimination using the K+ channel opener lemakalim. AB - Mast cell degranulating (MCD) peptide and Dendrotoxin I (DTXI), two potent hyperexcitability-inducing toxins acting on voltage-dependent potassium channels, induce the expression of both c-fos and c-jun mRNA in i.c.v. treated rats. The distribution of c-fos and c-jun expression has been analyzed by in situ hybridization. The expression is particularly high in the cerebral cortex and hippocampus for both toxins. However differences of expression between MCD and DTXI-treated animals have been observed in hypothalamus and thalamic and amygdaloid nuclei. Moreover, brain areas such as cerebellum which have high amounts of binding sites for both MCD and DTXI do not show any induction of c-fos and c-jun. Lemakalim, a K+ channel opener, prevents the MCD-induced activation of both 'immediate-early genes' in all brain areas but is unable to inhibit the induction of c-fos and c-jun induced by DTXI. These two toxins which are generally believed--from molecular approaches--to act on the same voltage dependent K+ channel, clearly act in vivo on two distinct classes of channels. PMID- 1933304 TI - The anticonvulsant valproate teratogen restricts the glial cell cycle at a defined point in the mid-G1 phase. AB - Direct cell counting and extent of [3H]thymidine incorporation demonstrated valproate to inhibit C6 glioma proliferation rate in a dose-dependent manner with a 1 mM concentration achieving 50% inhibition. The antiproliferative effect was reversible and could not be attributed to cytotoxicity at the valproate concentrations employed. The site of valproate action within the cell cycle was determined to be in the G1 phase, at a point 6-6.5 h prior to S phase, by estimating the time to increased [3H]thymidine incorporation following release from a 70% proliferative arrest. Synchronised cells obtained by a mitotic selection procedure required 11-12 h to enter S phase and demonstrated the valproate restriction point to be 5 h into the G1 phase of the C6 cell cycle. Exposure of valproate to the part of the G1 period which follows the restriction point was without effect on cell entry into S phase. PMID- 1933305 TI - Transport of iodothyronines from bloodstream to brain: contributions by blood:brain and choroid plexus:cerebrospinal fluid barriers. AB - Thyroid hormone entering the brain from the cerebral circulation must first cross barriers at the the blood:brain and choroid plexus:cerebrospinal fluid interfaces. The route taken after entry through those barriers might bring about selective delivery of hormone to different regions of the brain and those differences might be crucial for the ultimate functional effects of the hormone. To determine whether and how distribution of hormone in the brain might vary according to the route of entry, film autoradiograms of serially sectioned brains were prepared after delivery of a pulse of 125I-labeled thyroid hormone into either the right lateral cerebral ventricle or the femoral vein. The results after intrathecal injection, reflecting the penetration of hormone into brain after crossing the choroid plexus:cerebrospinal fluid barrier, revealed a markedly limited, essentially periventricular distribution of radioactivity at both 3 and 48 h after hormone administration. Results after i.v. administration, which allows hormone access across both barriers, revealed an initial distribution pattern (at 3 h) generally similar to that seen after administration of markers of cerebral blood flow; at 48 h there was strong resolution in selected brain regions never noted to be labeled after intrathecal hormone injection. The functional implications of the differences in results produced by the two different routes of hormone entry are not known. However, ready access to circumventricular organs would appear to be favored by hormone crossing the choroid plexus:cerebrospinal fluid barrier whereas access to the panoply of nuclear triiodothyronine receptors would be favored by hormone crossing the blood:brain barrier. Therefore both routes of barrier transport should be taken into account in assessing the kinetics and actions of thyroid hormones in the central nervous system. PMID- 1933306 TI - Parvalbumin in the monkey striate cortex: a quantitative immunoelectron microscopy study. AB - Parvalbumin (PV) is present in a subpopulation of interneurons in the visual cortex, and also in thalamic afferents to the neocortex of primates. The object of this study is to confirm by immunoelectron-microscopy the presence of intrinsic and extrinsic connections containing parvalbumin in the monkey visual cortex, by the demonstration of parvalbumin-immunoreactivity in symmetric and asymmetric synapses. We analyzed the distribution of parvalbumin-immunoreactive profiles at the ultrastructural level in the primary visual cortex of old world monkeys (Macaca fascicularis). It has been shown by others that parvalbumin immunoreactive cells resemble non-spiny stellate cells, double-bouquet cells, chandelier and basket cells. These neurons are known to be inhibitory and to form symmetric synapses. In fact, we observed that the vast majority of parvalbumin immunoreactive synaptic contacts in the primary visual cortex of Macaca fascicularis are of the symmetric type (81.7%). Since parvalbumin-positive asymmetric contacts are also present (18.3%) and occur mostly in the thalamic recipient layers, 4C and 4A (9.9%), these afferents probably derive from parvalbumin-immunoreactive neurons located in the dorsal lateral geniculate nucleus of the thalamus. PMID- 1933307 TI - Colchicine-induced cholinergic denervation of the hippocampus elicits sympathetic ingrowth. AB - Sympathetic neurons from the peripheral nervous system invade the hippocampus following destruction of its septal inputs. It is thought that sympathetic ingrowth is due to the loss of cholinergic innervation since damage to the medial septum-diagonal band complex (MSDB) or its major efferent bundle, the fimbria fornix, is required to induce ingrowth. The MSDB provides the major source of cholinergic fibers projecting to the hippocampus; however, non-cholinergic (e.g. GABAergic) neurons are also present in the MSDB and project to the hippocampus. Thus, the role of cholinergic denervation in sympatho-hippocampal sprouting cannot be directly tested by non-specific lesion techniques. In the present study, colchicine, which has been demonstrated to be specifically toxic to cholinergic neurons in the medial septum, was injected into each lateral ventricle of female Sprague-Dawley rats. Following colchicine-induced degeneration of cholinergic septohippocampal neurons, coarse, branched fibers immunoreactive for dopamine-beta-hydroxylase were observed predominantly in the dentate gyrus, on both sides of the granule cell layer, with increasing density as survival time increased. These results support the hypothesis that the invasion of the hippocampal formation by sympathetic fibers results from cholinergic denervation. PMID- 1933308 TI - Increase in nerve growth factor-like immunoreactivity and decrease in choline acetyltransferase following contusive spinal cord injury. AB - We have previously described a graded spinal cord injury model in the rat. Mild contusive injury results in an initially severe functional deficit that is attenuated over time to reveal the mild chronic deficits that characterize this injury. In this study, we have shown that mild contusive injury also results in a significant decrease in choline acetyltransferase (ChAT) activity during the first week after injury. At 1 week ChAT activity is maximally reduced at the site of the contusion and is also significantly lowered throughout the spinal cord. ChAT activity then rebounds during the following 3 weeks, partially at the injury site where there is considerable loss of gray and white matter, and completely in rostral and caudal cord segments. The rebound in ChAT activity is temporally associated with the partial recovery of function. Further, the changes in ChAT activity after injury are mirrored by changes in nerve growth factor-like immunoreactivity (NGF-LI) as determined by a specific two-site ELISA. NGF-LI increases significantly after injury, reaching a maximum at 7 days after contusion and at the injury site. However, levels of NGF-LI are also significantly increased throughout the spinal cord. NGF-LI then decreases at 2 and 4 weeks as ChAT activity rebounds. Further experiments will be needed to examine the possibility of a role for NGF in promoting the recovery of function after spinal cord injury. PMID- 1933309 TI - Comparison of visual sensitivity for suppression of pineal melatonin and circadian phase-shifting in the golden hamster. AB - Visual sensitivity for light suppression of pineal melatonin was measured in golden hamsters using 300 s stimuli of monochromatic light (503 nm) in constant darkness. Increasing stimulus irradiance caused a monotonic decrease in pineal melatonin content. Irradiance greater than 3.5 X 10(10) photons cm-2.s-1 caused significant reductions of melatonin in the hamster pineal. Saturation of the response occurred above 10(11) photons cm-2.s-1 and melatonin levels were suppressed to approximately 7% of levels measured in unstimulated animals. Using a 4-parameter Naka-Rushton function to fit the data, the half-saturation constant for suppression of pineal melatonin was 1.3 x 10(10) photons cm-2.s-1. The sensitivity of the photic-entrainment pathway for circadian rhythms has also been measured in the hamster using identical stimulus parameters. Light suppression of pineal melatonin was 25 times (1.4 log units) more sensitive to irradiance than the phase-shifting response measured for the circadian rhythm of running-wheel activity (comparing the half-saturation constants for the two responses). Both of these responses, however, are much less sensitive to light than other visual responses measured behaviorally in the golden hamster. PMID- 1933310 TI - Hippocampal grafts into the intact brain induce epileptic patterns. AB - Spontaneous hippocampal EEG activity and evoked field potentials were investigated in intact rats and in animals with fetal hippocampal grafts. Pieces of hippocampal grafts, derived from 15- to 16-day-old fetuses, were used to prepare cell suspensions and grafted directly into the intact hippocampus. Control animals received suspension grafts of the cerebellum derived from fetuses of identical age. Host hippocampal electrical patterns were monitored with chronic single electrodes or with a 16-microelectrode probe from 7 to 10 months after grafting. In contrast to previously reported high survival rates of fetal grafts in studies with damage to the host brain prior to grafting, survival of both hippocampal (60%) and cerebellar grafts (20%) was very poor in the intact hippocampus. In animals with cerebellar transplants or without surviving grafted neurons the electrical activity of the host hippocampus was indistinguishable from normal controls. In rats with hippocampal grafts short duration, large amplitude EEG spikes (up to 10 mV) were recorded, predominantly during immobility. When the EEG spikes (putative interictal spikes) were of large amplitude and contained population spikes, test evoked responses delivered to the perforant path were suppressed after the spontaneous events. In contrast, evoked responses were facilitated by interictal spikes without population spikes. The threshold of electrically induced afterdischarges did not differ significantly between groups of intact rats and animals with or without hippocampal grafts. However, in three rats with hippocampal grafts the evoked afterdischarges were associated with behavioral seizures. In two of these rats spontaneously occurring seizures were also observed. Synaptophysin-immunoreactivity demonstrated growth of the host mossy fibers into the graft.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933311 TI - Maintenance of peripheral dendrites of GABAergic neurons requires specific input. AB - This study demonstrates that the removal of a major hippocampal afferent system, the fibers from the entorhinal cortex, results in transneuronal changes in postsynaptic GABAergic inhibitory neurons. Following swelling of their distal segments, the peripheral dendrites of these cells retract from the termination zones of degenerating entorhinal fibers in the outer molecular layer of the fascia dentata and in stratum lacunosum-moleculare of the hippocampus proper. These dendritic alterations are long-lasting and do not seem to be restored by sprouting of other intact afferents. Persisting transneuronal changes in GABAergic hippocampal neurons following the removal of their entorhinal afferents may play a role in Alzheimer's disease since there is a severe degeneration of the entorhino-hippocampal projection in this neurodegenerative disorder. PMID- 1933312 TI - Effects of aldosterone or RU28362 treatment on adrenalectomy-induced cell death in the dentate gyrus of the adult rat. AB - Previous studies have shown that granule cells of the adult dentate gyrus require adrenal steroids for their survival. In order to investigate whether activation of type I or type II adrenal steroid receptors can mediate granule cell survival, we have analyzed the density of pyknotic cells in the granule cell, CA1 and CA3 pyramidal cell layers in Nissl stained hippocampal sections from adult male rats which were either sham operated, adrenalectomized, or adrenalectomized and treated with aldosterone as a specific type I receptor agonist or RU28362 as a specific type II receptor agonist. Aldosterone treatment completely protected the dentate gyrus from adrenalectomy-induced cell death, while treatment with RU28362 resulted in only a partial protection against cell death in this region. These results indicate that type I adrenal steroid receptor activation is sufficient to protect against adrenalectomy-induced cell death. PMID- 1933313 TI - A possible fetal antigen of Mr 70,000 in neurofibrillary tangles. AB - To test the hypothesis that tau-immunoreactive curly fibers represent a regenerative attempt of cortical neurons in the brain affected with Alzheimer's disease (AD), we established 2 monoclonal antibodies to isolated neurofibrillary tangles. Both antibodies extensively stained curly fibers and specifically labeled a novel protein of Mr 70,000 (p70), which was abundantly expressed in fetal brain, but undetectable in adult brain. Furthermore, the antibodies visualized curly fibers in newborn rat brain, which were very similar to those in the AD brain, and also intensely stained extending neurites of NGF-primed PC 12 cells. These observations suggest that P70 is a fetal antigen associated with growing neurites, and thus support the sprouting hypothesis. PMID- 1933314 TI - Calcium binding protein immunoreactivity in a reptilian thalamic reticular nucleus. AB - Immunoreactivity to antisera directed against a variety of calcium binding proteins was investigated in the thalamic reticular nucleus of one species of reptiles, Caiman crocodilus. Cells and fibers were immunoreactive for parvalbumin whereas fibers but not neurons were immunoreactive for calbindin and calcitonin gene related peptide. These data support the observations that Caiman thalamic reticular nucleus contains at least two neuronal populations. One group, whose cells are immunoreactive for parvalbumin, forms at least part of the projection to the dorsal thalamus. The other group, which contains qualitatively different and sparser number of neurons, is immunoreactive for glutamic acid decarboxylase. PMID- 1933315 TI - Activation of nigral M1 and M2 muscarinic receptors produces opposing effects on striatal 3,4-dihydroxyphenylacetic acid measured by in vivo voltammetry. AB - 3,4-dihydroxyphenylacetic acid (DOPAC) was measured by differential pulse voltammetry in the neostriatum of anesthetized rats. DL-Muscarine (2.9 nmol) applied into the substantia nigra pars compacta, increased DOPAC concentration in the ipsilateral neostriatum. This effect was blocked by pirenzepine (2.8 nmol), and potentiated by AF-DX 116 (2.8 nmol). These results indicate the existence of two types of muscarinic receptors on dopaminergic neurons, whose activation produces opposing effects on dopamine metabolism in neostriatum. PMID- 1933316 TI - In vivo evidence for carrier-mediated brain uptake of a new 2-amino-2-oxazoline (COR3224) via the purine transport system in rat. AB - We studied the brain uptake of a new 2-amino-2-oxazolamines derivative (COR3224) in the rat by means of the rapid intracarotid injection technique described by Oldendorf. The brain uptake index (BUI) of labelled COR3224 decreased progressively from 10% to 5% when concentrations of unlabelled compound were increased. The effect of various compounds indicated that COR3224 is transported into the brain by the purine carrier. The affinity of COR3224 for this carrier (Km = 5.68 microM) was higher than that of adenine. PMID- 1933317 TI - Brain corticotropin-releasing hormone increases arousal in stress. AB - The effect of restraint stress on pentobarbital-induced sleeping time was examined in rats. Restraint for 60 and 75 min significantly shortened pentobarbital-induced sleeping time. The shortening of sleeping time by restraint was completely reversed by intracerebroventricular (i.c.v.) administration of alpha-helical CRH(9-41), a corticotropin-releasing hormone (CRH) receptor antagonist. In conjunction with our previous finding that i.c.v. administration of CRH shortens pentobarbital-induced sleeping time, the results suggest that restraint stress increases arousal through brain CRH. PMID- 1933318 TI - Relationships between indices of behavioral asymmetries and neurochemical changes following mesencephalic 6-hydroxydopamine injections. AB - Behavioral and neurochemical changes were investigated in rats that had received one of 3 doses of 6-hydroxydopamine (6-OHDA), injected unilaterally into the ventral mesencephalon. The behavioral analysis comprised that of tight turns (diameter less than 30 cm), wide turns (diameter greater than 55 cm), and locomotor activity. 6-OHDA-injected animals were assigned to 3 different groups according to their degree of asymmetry in tight turns, both in spontaneous behavior and after the dopamine receptor agonist apomorphine (0.05 mg/kg). Thus, 6-OHDA-injected animals showed either (i) no spontaneous ipsiversive asymmetry (group 1), or (ii) an ipsiversive asymmetry, from which they did not recover during the three postoperative weeks of testing and which could not be reversed by apomorphine (group 2), or (iii) an even stronger ipsiversive asymmetry from which they did not recover but which could be reversed by apomorphine (group 3). The analysis of wide turns, which might reflect exploratory behavior of the environment, namely thigmotactic scanning, provided further information, as it indicated an asymmetry even in group 1; however, in contrast to the other groups a contraversive asymmetry was observed. Neurochemically, the three experimental groups were clearly different from each other with respect to the degree of neostriatal dopamine depletion, and the increase in dopamine metabolism in the damaged hemisphere as indicated by increased metabolite/transmitter ratios. The ipsiversive asymmetry in tight turns was negatively correlated with dopamine levels in the damaged neostriatum and positively correlated with the increase in metabolism. Furthermore, indications of changes in neostriatal serotonin activity were found. These results are discussed with respect to the necessity of differential measures of behavioral asymmetry, the role of dopaminergic mechanisms of 6-OHDA-induced deficits and mechanisms of recovery. The asymmetries in tight versus wide turns are suggested to reflect the preponderance of a motor deficit in the former case versus that of sensory neglect in the latter. Thus, the analysis of tight versus wide turns may provide distinctive and sensitive indices related to different functional deficits in animal models of hemiparkinsonism. PMID- 1933319 TI - Evidence for the involvement of protein kinase C in the modulation of morphine induced 'analgesia' and the inhibitory effects of exposure to 60-Hz magnetic fields in the snail, Cepaea nemoralis. AB - There is substantial evidence that magnetic fields can reduce opiate-induced analgesia, with alterations in calcium channel function and/or calcium ion flux being implicated in the mediation of these inhibitory effects. The present experiments were designed to examine the effects of protein kinase C (PKC), a calcium/diacylglycerol/phospholipid-dependent protein kinase, on opiate-induced analgesia and its involvement in mediating the inhibitory effects of exposure to magnetic fields. We observed that morphine-induced antinociception, or 'analgesia', in the land snail, Cepaea nemoralis, as measured by the enhanced latency of response to a thermal (38.5 degrees C) stimulus, was reduced in dose related manner by the PKC activator, SC-9. Exposure of snails for 2 h to a low intensity (1.0 gauss rms) 60-Hz magnetic field also reduced morphine-induced analgesia. The inhibitory effects of the 60-Hz magnetic field on morphine-induced analgesia were significantly reduced by the PKC inhibitors, H-7 and H-9, and significantly enhanced by the PKC activator, SC-9. The non-specific protein kinase inhibitor, HA-1004, and the preferential calmodulin inhibitor, W-7, had no significant effects on either morphine-induced analgesia or the inhibitory actions of exposure to the magnetic fields. These results suggest that: (1) PKC has antagonistic effects on opiate-mediated analgesia in the snail, Cepaea, and (2) that the inhibitory effects of magnetic fields on opiate-induced analgesia involve alterations in PKC. PMID- 1933321 TI - Luminance coding properties of intergeniculate leaflet neurons in the golden hamster and the effects of chronic clorgyline. AB - Cells in the intergeniculate leaflet (IGL) project to the suprachiasmatic nuclei, a mammalian circadian pacemaker. Chronic treatment with clorgyline alters hamster circadian rhythms in ways similar to alterations seen after ablation of the IGL. Chronic clorgyline also alters the light intensity dependence of phase-shifting. In this study luminance coding properties of IGL cells were measured in control hamsters and in hamsters chronically treated with clorgyline. In control animals three patterns of response to increasing and decreasing luminance were observed. Type I cells showed a monotonic pattern. Type II cells were similar to Type I with additional increases in firing rate at several specific luminance levels. Type III cells only coded increases in luminance. Cells from clorgyline-treated animals did not differ from those from control animals in the pattern of luminance response but IGL cells from these animals showed decreased firing rate in both light and dark conditions. These results suggest that the effects of clorgyline on the photic sensitivity of circadian rhythms may be related to a clorgyline-induced decrease in firing rate of IGL cells. They also indicate that some IGL cells show complex patterns of response to luminance changes in addition to those showing simple monotonic responses. PMID- 1933320 TI - Dopamine receptors in the ventral tegmental area affect motor, but not motivational or reflexive, components of copulation in male rats. AB - Microinjection of apomorphine into the ventral tegmental area (VTA) of male rats was previously shown to delay the onset of copulation and slow its rate, presumably by stimulating impulse-regulating autoreceptors on cell bodies of the A10 mesocorticolimbic dopamine tract. Such stimulation would be expected to slow the firing rate of these neurons and, thereby, to impair locomotion and/or motivational processes. The present experiments tested whether the delayed onset and slowed rate of copulation were related to deficits in motor performance, sexual motivation, and/or genital reflexes. In X-maze tests the speed of running to all 4 goal boxes was slowed; however, the percentage of trials on which the male chose the female's goal box was not decreased. Examination of videotaped copulation tests revealed that the male showed fewer complete copulatory behaviors (mounts, intromissions, and ejaculations), but more misdirected or incomplete copulatory attempts after apomorphine in the VTA. There were also fewer scores of active, as opposed to inactive, behaviors, and the onset and rate of copulation were slowed. The total number of female directed behaviors was not different in apomorphine tests, compared to vehicle. Finally, tests of ex copula genital reflexes revealed no significant effects of apomorphine in the VTA on erections, penile movements, or seminal emissions. These data suggest a role of the VTA in the motor aspects and/or sensorimotor integration of copulation. Sexual motivation and ex copula genital reflexes appeared to be unaffected by apomorphine in the VTA. PMID- 1933322 TI - Polysaccharides as taste stimuli: their effect in the nucleus tractus solitarius of the rat. AB - Rats show a pronounced preference for the tastes of starch-derived polysaccharides. Three of these compounds--Polycose, maltotriose and amylopectin- were used along with a standard array of chemicals in a study of their effectiveness as taste stimuli, as monitored by evoked single unit activity in the nucleus tractus solitarii (NTS). Maltotriose and amylopectin elicited very few spikes and no clear quality-related pattern of neural activity. Polycose, however, was an effective taste stimulus. It evoked an activity profile across neurons and over time that was poorly correlated with that of the prototypical sugar (sucrose) and only moderately related to those of the non-sugar prototypes (NaCl, HCl and quinine-HCl). The 14 cells (23%) that responded particularly well to Polycose were all members of neuronal subgroups that emphasized salt, acid and quinine sensitivity. Thus, despite the strong behavioral preference shown to Polycose, its neural profile is unlike those of other preferred stimuli. Polycose may represent a unique taste stimulus whose quality cannot be readily associated with those of the traditional 4 basic tastes. PMID- 1933323 TI - How long does 'memory consolidation' take? New compounds can improve retention performance, even if administered up to 24 hours after the learning experience. AB - The 'nootropics' are a new class of psychoactive substances that improve learning and memory. Their almost exclusive effect on memory may indicate that they act on processes specifically involved in information storage. When administered after the learning trial, these substances improve subsequent retention performance in mice, even if an interval of 8 h has elapsed between learning and treatment. CGS 5649B, a highly active new substance, is effective even after an interval of 24 h. Although consonant with the 'consolidation' hypothesis, the results may challenge prevailing notions about the formation of memory traces. PMID- 1933324 TI - Efferent control of posterior canal afferent receptor discharge in the frog labyrinth. AB - EPSP and spike discharges were intracellularly recorded from 90 afferent fibres of the posterior nerve in the isolated frog labyrinth and the effects of electrical activation of the efferent system were tested. Posterior canal efferent synapses were activated, via an axon reflex, by electrical shocks to the anterior-horizontal nerves. The afferent resting discharge of all fibres tested was affected by efferent stimulation: 39 units were inhibited (43%) and 51 (57%) were facilitated. The efferent system was activated with several stimulation frequencies in the 10-200 Hz range applied for different times (250 ms-10 s). By changing the stimulus parameters, inhibition did not reverse to facilitation or vice versa. Facilitation appeared within the train above a threshold frequency of about 10 Hz. The peak response was readily reached within the first second and then, with long lasting stimulation, a marked adaptation ensued. The increase in firing rate was independent of previous resting activity. The relationship between frequency and facilitatory response is described by a logarithmic function over the 30-200 Hz range tested. At the end of short trains a consistent post-stimulation after-discharge appeared, whose intensity is positively related to stimulation frequency and time. Inhibition was achieved at stimulation rates above 10 Hz, and a post-stimulation rebound discharge was evident, which was linearly dependent on previous stimulation rate. The latency values of both inhibitory and facilitatory effects were measured by taking into account either the EPSP release rate or the spike discharge modifications at all the frequencies tested. Latency proved to decrease exponentially with increasing stimulation time from a minimal value of 3 ms to a maximum of 200 ms, with minor differences between inhibition or facilitation. These long latency values, the presence of a threshold frequency and the stimulus- and frequency dependence indicate that the efferent synapses must be activated repetitively to produce detectable effects on the afferent discharge; this is in line with the discharge pattern of the efferent system fibres physiologically measured in some systems. The present results show that the dual central control of the crista ampullaris of frog posterior canal is potentially capable of setting the receptor population at a variable level of sensitivity to mechanical stimuli, with profound modifications in the canal transfer function and the spike encoding mechanism. PMID- 1933325 TI - Long-lasting potentiations evoked by a brief heterosynaptic tetanus in the guinea pig dentate gyrus in vitro. AB - The heterosynaptic effects induced by a brief afferent tetanization in the molecular layer of the dentate gyrus were investigated in the guinea pig hippocampal slice preparation using extracellular recording technique. At a brief interval (5 ms) between a single stimulation of the test afferents and the tetanus evoked in the conditioning afferents, a long-lasting (greater than 1 h) potentiation of the test field excitatory postsynaptic potential (EPSP) initial slope and amplitude was observed. This potentiation was occluded by prior homosynaptic tetanization of the test afferents, suggesting that it represents long-term potentiation (LTP). Thus, in the dentate gyrus, a single activation of a single test EPSP suffices to induce LTP when coinciding in time with a brief tetanus to other afferents. When not temporally paired with the test stimulation, i.e. at longer test-conditioning intervals (greater than 50 ms), the conditioning tetanus also elicited a long-lasting potentiation of the test field EPSP. This potentiation was, however, seen as a prolongation of the rising phase with no change in the field EPSP initial slope, and may represent a potentiation distinct from LTP. PMID- 1933326 TI - Correlation of MPTP neurotoxicity in vivo with oxidation of MPTP by the brain and blood-brain barrier in vitro in five rat strains. AB - We studied 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in 5 strains of rats by assessing mortality and brain monoamine changes after MPTP injections into the internal carotid artery. We then attempted to correlate the differences among rat strains in their susceptibility to MPTP neurotoxicity in vivo with MPTP oxidation by monoamine oxidase (MAO) of the cerebral cortex, striatum, and brain microvessels in vitro. Despite the fact that the carotid route delivers much higher amounts of MPTP to the ipsilateral cerebrum than can be achieved by systemic injections, no significant dopamine depletion occurred in ipsilateral striata of Sprague-Dawley rats (the most resistant strain), but significant reductions of about 40% in striatal dopamine were evident in the more sensitive strains. Decreased striatal dopamine levels in these latter rat strains were associated with increased dopamine turnover. Higher doses of MPTP resulted in acute death. MPTP-induced mortality was not affected, but striatal dopamine depletion was prevented, by MAO inhibition. Differences among rat strains in their susceptibility to MPTP neurotoxicity correlated best with MAO activity in their isolated brain microvessels, but not with MAO activity in their striata or cerebral cortices. These results are consistent with the hypothesis that the rats' resistance to MPTP neurotoxicity is to some extent a property of their unique brain endothelium which has high MAO activity. PMID- 1933327 TI - Activation of noradrenergic locus coeruleus neurons by hemodynamic stress is due to local release of corticotropin-releasing factor. AB - The present study was designed to determine whether activation of locus coeruleus (LC) neurons by hemodynamic stress is mediated by local release of corticotropin releasing factor (CRF) within the LC. The ability of local LC injection of the CRF antagonist, alpha helical CRF9-41, to prevent LC activation elicited by i.v. nitroprusside infusion was investigated in halothane-anesthetized rats. Nitroprusside infusion (10 micrograms/30 microliters/min for 15 min) consistently increased LC spontaneous discharge rate with the mean maximum increase of 32 +/- 5% (n = 8) occurring between 3 and 9 min after the initiation of the infusion. Prior local LC injection of alpha helical CRF9-41 (150 ng), but not of saline (150 nl), prevented LC activation by nitroprusside. Alpha helical CRF9-41 did not alter LC spontaneous discharge rate or LC discharge evoked by repeated sciatic nerve stimulation suggesting that the CRF antagonist selectively attenuates stress-elicited LC activation. In contrast to alpha helical CRF9-41, the excitatory amino acid antagonist, kynurenic acid, did not attenuated LC activation by nitroprusside at a dose (0.5 mumol in 5 microliters, i.c.v.) that prevented LC activation by sciatic nerve stimulation. Taken together, these findings suggest that hemodynamic stress elicited by nitroprusside infusion activates LC neurons by releasing CRF within the LC region. The onset of LC activation by nitroprusside was temporally correlated with electroencephalographic (EEG) activation recorded from the frontal cortex and hippocampus. EEG activation was characterized by a change from low frequency, high amplitude activity to high frequency low amplitude activity recorded from the cortex and theta rhythm recorded from the hippocampus. LC activation usually outlasted the EEG activation. Nitroprusside infusion following local LC injection of alpha helical CRF9-41 was also associated with EEG activation in most rats. However, the duration of hippocampal theta rhythm was shorter in rats administered alpha helical CRF9-41. Thus, LC activation during cardiovascular challenge may play some role in EEG activation but is not necessary for this effect. PMID- 1933328 TI - Intrathecal coadministration of clonidine with serotonin receptor agonists produces supra-additive visceral antinociception in the rat. AB - The intrathecal (i.t.) coadministration of sub-antinociceptive doses of clonidine, an alpha 2-adrenoceptor agonist, with DOI or RU-24969 (5-HT2 or 5-HT1B receptor agonists, respectively) produced dose-dependent supra-additive antinociceptive effects in a model of visceral pain. The enhanced attenuation of responses to noxious colorectal distension produced by the coadministration of these drugs is evidenced by significant leftward shifts in the dose-response curves as compared to those of each drug alone and by isobolographic analysis. The supra-additive antinociceptive effects produced following the i.t. coadministration of clonidine with RU-24969 were antagonized by i.t. pretreatment with phentolamine; the coadministration of phentolamine with methysergide produced no greater antagonism of effects. The supra-additive antinociceptive effects produced by i.t. coadministration of clonidine with DOI were antagonized by i.t. pretreatment with methysergide; the coadministration of methysergide with yohimbine produced no greater antagonism of effects. These data suggest that receptors acted upon by descending bulbospinal neurons interact to modulate the rostrad transmission of visceral nociceptive transmission. PMID- 1933329 TI - Genetic and phenotypic heterogeneity of inherited spike-wave epilepsy: two mutant gene loci with independent cerebral excitability defects. AB - Two recessive gene loci controlling cerebral excitability in the mouse (tg, chr 8 and stg, chr 15) share generalized neocortical spike-wave seizures as a common mutant phenotype. Although the primary molecular defects are unknown, homozygous tg mutants display a gene-linked hyperplasia of central noradrenergic axons originating in the locus ceruleus, and early selective lesions of these fibers correct the epileptic phenotype in the adult. In contrast, we find that stg homozygotes, despite a more severe seizure disorder, show no alterations in regional noradrenergic fiber innervation, and seizure frequency is unaffected by neonatal noradrenergic depletion. These mutations demonstrate that excessive synchronous neuronal discharges alone are insufficient to trigger abnormal growth of locus ceruleus fibers, and reveal the existence of two distinct intervening brain neuromodulatory mechanisms, norepinephrine (NE)-dependent and NE independent, underlying the inheritance of this common pattern of epilepsy. PMID- 1933330 TI - Glucose concentration inversely alters neocortical slice excitability through an osmotic effect. AB - Neurological problems can develop when blood glucose levels rapidly rise or fall yet there has been little experimentation at a cellular level to assess how neurophysiological change may be induced. Using intracellular recording in the rat neocortical slice preparation, we examined pyramidal neurons of layers II-III as saline D-glucose concentration was altered. Single cell properties, synaptic transmission and epileptiform discharges were studied in control saline and compared with corresponding data when osmolality was raised with D-glucose by 20 80 mOsm. Although single cell properties were not significantly altered, the amplitude of evoked early and late EPSPs were proportionally reduced within 5 min. A similar but more pronounced effect was observed with mannitol, whereas freely permeable dimethylsulfoxide (DMSO) was without effect. Hyposmolality increased the amplitude of evoked early and late EPSPs. Therefore the dampening of synaptic transmission by D-glucose appears osmotic in origin. D-glucose was osmotically effective only above 30 mM probably because it is cell-permeable at lower concentrations. In slices made epileptogenic by Mg(2+)-free saline, increasing D-glucose decreased the frequency and increased the duration of interictal bursts. Again mannitol mimicked the glucose effects and hyposmotic change gave opposing responses. The inverse relation between glucose concentration and neocortical excitability correlates well with clinical observations that an acute reduction in blood glucose from hyperglycemic levels (as follows insulin over-administration) can evoke generalized seizure. PMID- 1933331 TI - Monosynaptic connection from caudal to rostral ventrolateral medulla in the baroreceptor reflex pathway. AB - Experiments were done to test the hypothesis that caudal ventrolateral medulla (CVLM) neurons excited by activation of arterial baroreceptors and by stimulation of depressor sites in the nucleus tractus solitarii (NTS) project monosynaptically to the rostral ventrolateral medulla (RVLM). In urethan anaesthetized and artificially ventilated rats we recorded extracellular activity from 46 spontaneously firing units in the CVLM. Twenty of these units were excited by baroreceptor activation (1-3 micrograms phenylephrine i.v.) and of these 6 were excited (mean latency of 9.8 +/- 2.3 ms) by single pulses (0.1 ms, 30 +/- 8.3 microA) delivered once per second to a depressor site in the ipsilateral NTS. These 6 units were also antidromically activated with a latency of 4.1 +/- 0.12 ms by stimulation of a pressor region in the ipsilateral RVLM. These results provide evidence for the existence of an excitatory projection from the NTS to the CVLM which, in turn, projects monosynaptically to sympathoexcitatory neurons in the RVLM. PMID- 1933332 TI - Responses of cat C1 spinal cord dorsal and ventral horn neurons to noxious and non-noxious stimulation of the head and face. AB - Previous anatomical studies have shown that trigeminal and cervical afferent nerve fibers project to the upper cervical segments of the spinal cord. To determine the response properties of neurons in the upper cervical spinal cord, we studied the response of C1 dorsal and ventral horn cells to electrical and graded mechanical stimulation of the face, head and neck in anesthetized cats. Neurons were classified as low-threshold-mechanoreceptive (LTM), wide-dynamic range (WDR), nociceptive-specific (NS) or unresponsive, based on their responsiveness to graded mechanical stimulation. Extracellular single unit recordings were obtained from 118 neurons excited by cervical (24), trigeminal (39) or both cervical and trigeminal (55) stimulation and from 24 neurons unresponsive to peripheral stimulation. Based on neuronal mechanical response properties, 52.2% of the responsive neurons were classified as LTM, 35.9% as WDR and 11.9% as NS. WDR neurons exhibited more convergence and had larger receptive fields than either NS or LTM neurons. WDR and NS neurons had longer first spike latencies than LTM neurons at all tested sites. Only WDR neurons were found to project to the contralateral caudal thalamus. Within C1, LTM neurons were located primarily in laminae III and IV, WDR neurons in lamina V and NS neurons in laminae VII and VIII. These data suggest that some neurons in the first cervical segment of the spinal cord receive convergent input from trigeminal and cervical pathways and may be involved in mediating orofacial and cranial pain. PMID- 1933333 TI - Insulin and the paraventricular hypothalamus: modulation of energy balance. AB - The effects of insulin injections (0.1, 1, 10 and 40 mU) into the paraventricular hypothalamus (PVN) were investigated in an open-circuit calorimeter. Wistar rats were tested, with no food available during the tests. The 0.1 and 1 mU doses had no effects on either respiratory quotient or energy expenditure. The 10 mU dose increased respiratory quotient which indicates increased dependency on carbohydrates as an energy substrate. The same dose had no effects on thermogenesis. In contrast, the 40 mU dose decreased respiratory quotient which indicates increased dependency on fats as an energy substrate. The higher dose also increased thermogenesis. Since neither dose significantly affected locomotor activity, the metabolic data are not confounded with activity effects. These data indicate that insulin in the PVN produces a primary modulation of the metabolic parameters central to maintaining energy balance. In separate experiments, the 4 doses of insulin reduced food intake and body weight over a 24 h period. They also produced a dose-related increase in blood glucose concentration over a one hour period. Taken together, these findings are interpreted in a model in which insulin in the PVN acts as a signal indicating increased body fat. This increases thermogenesis, fat utilization and glycemic levels, and inhibits feeding. The net effect of this integrated metabolic-behavioural response is a regulatory reduction in body fat. PMID- 1933334 TI - Coordination of motor pools controlling the ankle musculature in adult spinal cats during treadmill walking. AB - The coordination of the motor pools of two ankle plantar-flexor, i.e. the soleus (Sol) and medial gastrocnemius (MG), and an ankle dorsiflexor, i.e. the tibialis anterior (TA) was quantified by comparing the EMG amplitude relationships in muscle pairs in normal and trained adult spinalized cats during treadmill walking across a range of relatively slow speeds (0.1 to 1.0 m/s). The effects of increased tactile stimulation or loading on locomotor performance were also studied in the spinal cats. Joint probability density distributions in the spinalized cats showed a low level of MG activation relative to Sol which did not change as speed increased. In general, the coordination between Sol and MG was similar in normal and spinal cats. However, towards the final phase of the extensor burst, the MG EMG amplitude decayed prematurely in spinal cats, particularly at higher speeds. Preferential elevation of MG relative to Sol activity was seen as a result of tactile stimulation. An elevated load resulted in a higher level of MG activation relative to Sol, prolonged MG activity at the end of the extensor burst, and the reduction in the clonic pattern of EMG typical of spinal cats. Spinalized cats showed an increased incidence of Sol-TA coactivation, especially at the higher speeds, due in part to the tonic activity in the TA. However, the overall reciprocal relationship between these antagonists was maintained. This reciprocity was preserved, but the high level of coactivation was unaffected by tactile stimulation. An elevated load, however, resulted in less Sol-TA coactivation. These results suggest that the coordination between synergists (Sol-MG) and between antagonists (Sol-TA and MG-TA), as well as the level of activation are modulated in the adult spinal cat similar to that observed in the normal cat. Further, there are specific types of proprioceptive cutaneous information that can affect selected phases of the step cycle such that full weight-supporting stepping is significantly improved. PMID- 1933335 TI - Protection and potentiation of MPTP-induced toxicity by cytochrome P-450 inhibitors and inducer: in vitro studies with brain slices. AB - Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes loss of dopaminergic neurons in humans, primates and mice. Exposure of sagittal slices of mouse brain to MPTP (100 pM) caused inhibition of mitochondrial NADH dehydrogenase activity. Leakage of lactate dehydrogenase from the slice into the medium was observed following incubation of slices with 1 nM MPTP. Neurotoxicity induced by MPTP was prevented by prior exposure of the slices to the dopamine uptake inhibitor GBR 12935. Deprenyl and pargyline (inhibitors of monoamine oxidase), also protected the slices from MPTP-induced toxicity. However, both pargyline and deprenyl also inhibited cytochrome P-450 mediated aminopyrine N demethylase activity in brain slices. Pargyline, when administered in vivo to mice, decreased brain cytochrome P-450 levels significantly. Other cytochrome P 450 inhibitors, namely, piperonyl butoxide and SKF 525A were found to offer protection against MPTP induced neurotoxicity in slices without affecting monoamine oxidase activity. MPTP toxicity was potentiated significantly in brain slices prepared from mice pretreated with phenobarbital, an inducer of cytochrome P-450. The present study suggests the possible involvement of cytochrome P-450 in MPTP-induced neurotoxicity, in vitro, in brain slices. PMID- 1933336 TI - Involvement of corticotrophin releasing factor (CRF) in the thermogenic and anorexic actions of serotonin (5-HT) and related compounds. AB - The present study investigated the involvement of corticotrophin-releasing factor (CRF) in the thermogenic and anorexic actions of serotonin (5-HT) in the rat. Serotonergic compounds and CRF antibody were injected directly into the third ventricle of conscious, male Sprague-Dawley rats. Thermogenesis was measured as changes in whole body oxygen consumption by indirect calorimetry. Central injections of 5-HT (0.5-50 micrograms, i.c.v.) significantly increased resting oxygen consumption (VO2; maximum 12.5% increase), without obvious effects on behaviour. Similar increases in VO2 (12-17%) were observed following central injections of the 5-HT precursors, tryptophan (14 micrograms, i.c.v.) or 5 hydroxytryptophan (5-HTP, 20 micrograms, i.c.v.), and peripheral (10 mg/kg, i.p.) or central (30 micrograms, i.c.v.) injections of the 5-HT reuptake inhibitor, DL fenfluramine. Administration of a polyclonal CRF antibody (3 microliters, i.c.v.) 10 min prior to serotonergic compounds, significantly reduced (77-106%) the increases in VO2 observed in response to central injections of 5-HTP (20 micrograms), 5-HT (50 micrograms) or peripheral injections of fenfluramine, but not those observed in response to either 30 micrograms fenfluramine (i.c.v.) or 20 micrograms 5-HT. Voluntary food intake was measured for 6 h in rats following 16 h starvation. Six-hour food intake was significantly reduced (30-60%) in rats given central injections of 5-HT or 5-HTP, and central or peripheral injections of fenfluramine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933337 TI - Spinal transection reduces both spinal antinociception and CNS concentration of systemically administered morphine in rats. AB - Within one day after spinal transection, the antinociceptive effect of systemically administered morphine on the spinal withdrawal reflex is significantly reduced. This observation has provided important empirical support for the present model of opiate-induced analgesia. One prediction from this model is that the antinociceptive effect of intrathecal (spinal) morphine injections should not be reduced by spinalization. When examined experimentally, this prediction was not supported; the antinociceptive effect of intrathecally administered morphine was significantly enhanced after acute spinalization. This result suggested an alternate hypothesis of morphine-induced analgesia. One prediction from this new hypothesis is that the decreased behavioral response to systemic morphine in spinal rats is due to a decrease in the spinal concentration of morphine produced by spinal transection. To test this prediction separate groups of intact rats and acute (one day) spinal rats, were assessed with the tail-flick (TF) procedure 60 min after subcutaneous injection of various doses of morphine (0.75, 1.5, 3.0, 4.5, 6.0 or 9.0 mg/kg) or at different time points (30, 60, 90, 150 or 240 min) after a single injection of 9.0 mg/kg. Immediately after behavioral testing, the rats were killed and brains, spinal cords and blood samples were collected and subsequently analyzed with a morphine radioimmunoassay. The results show that the concentration of morphine in the brain and spinal cords of acute spinal rats is significantly lower than that of intact rats, whereas morphine levels in the blood do not differ. These data suggest that the decreased antinociceptive effect of subcutaneous morphine in acute rats is due to a decrease in the concentration of the opiate in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933338 TI - Differences among effects of sedative-hypnotic drugs on GABA-mediated chloride flux: quench flow studies. AB - The effects of 40 microM pentobarbital (PB), 1 microM diazepam (DZ) and 50 mM ethanol (EtOH) on gamma-aminobutyric acid (GABA)-mediated chloride flux into rat cerebral cortical microsacs were studied during 50 ms incubations with 36Cl. A quench-flow machine was used, allowing for preincubations and incubation of precise duration. A 1 s preincubation with PB did not increase the already significant effect of PB on GABA-mediated flux during the 50 ms incubation, but the 1 s preincubation was necessary for showing the effect of diazepam. EtOH had no effect, whether or not it was added in the preincubation. When microsacs were preincubated with 32 microM GABA for 1 s, far greater potentiation of the GABA effect was seen when the PB was also present during the preincubation than when it was only introduced in the incubation. Preincubation with both DZ and GABA also had a greater effect than merely adding DZ into the incubation, after the preincubation with GABA. Ethanol had no effect when added either during or after the 1 s preincubation with GABA. The different effects of these sedatives on GABA mediated chloride flux are strongly suggestive of different loci or mechanisms of action. PMID- 1933339 TI - The effects of serotonergic stimulation on hippocampal and neocortical slow waves and behavior. AB - The effect of central serotonergic stimulation on hippocampal and neocortical electrical activity and behavior was studied in freely moving rats by administering: (a) tranylcypromine followed by tryptophan, (b) fluoxetine followed by 5-hydroxytryptophan, or (c) p-chloroamphetamine alone. In all rats, scopolamine-resistant hippocampal rhythmical slow activity (RSA), thought to be dependent on brain serotonin, maintained its normal relation to behavior, occurring in close correlation with Type 1 behaviors (postural changes, turning of the head, walking). This RSA was generally absent during stereotyped behavior (head weaving, forepaw treading, hindlimb splaying and tremor). Scopolamine resistant neocortical low-voltage fast activity (LVFA), also though to be dependent on brain serotonin, was present during Type 1 behaviors and also during stereotyped behavior. Most rats that developed a full stereotyped behavior syndrome had behavioral and electrocortical seizures which were associated with a reduction in the amplitude of hippocampal activity. These seizures were suppressed by methysergide or benserazide. Metergoline (and methysergide to a lesser extent) suppressed the stereotypic behaviors of the serotonin syndrome, resulting in a striking increase in the locomotion caused by central serotonergic stimulation. Such locomotion was accompanied by RSA and LVFA. It was concluded that increased serotonergic activity in the CNS causes an increase in motor activity and a correlated increase in scopolamine-resistant hippocampal RSA and scopolamine-resistant neocortical LVFA and suggested that metergoline blocks serotonin receptors mediating stereotyped behaviors, thereby permitting the expression of serotonin-mediated locomotion. PMID- 1933341 TI - Retinal distribution of ganglion cells which project to the ipsilateral optic tectum in Bufo marinus. AB - The retinotectal projection in anura is mainly crossed, although a small proportion of optic axons projects to the ipsilateral tectum. Using the fluorescent carbocyanide dye, DiI, we mapped the retinal topography of ganglion cells which project to the ipsilateral tectum in adult Bufo marinus. DiI was injected into particular locations in the right tectum. After 10 days survival both the right and the left retinals were wholemounted and the number and retinal position of retrogradely filled ganglion cells were determined. The contralateral and ipsilateral cells were visuotopically distributed in the retina in the majority of experiments. However, in two cases cells were located in visuotopically disparate parts of the retina. The ipsilateral cells represented 3.7% of contralaterally projecting cells in the temporal retina, 0.1% in the nasal and dorsal retina and 0.6% of the ventral retina. The density of ipsilaterally projecting ganglion cells varied from a top of 25 cells/mm2 in the temporal retina, 9 cells/mm2 in the nasal, 3 cells/mm2 in the dorsal to 11 cells/mm2 in the ventral retina. The diversity of size and shape of retrogradely filled ganglion cells indicated that the ipsilateral population corresponded to a heterogeneous class of ganglion cell types. The functional significance of the direct ipsilateral retinotectal projection of the anuran visual system has yet to be elucidated. However, in light of the involvement of the indirect ipsilateral retinotectal projection in binocular vision, the direct pathway is likely to be associated with a retino-tecto-spinal circuit subserving postural adjustment to visually derived stimulation. PMID- 1933340 TI - A brief period of hypoxia causes proteolysis of cytoskeletal proteins in hippocampal slices. AB - Breakdown products (BDPs) resulting from the partial proteolysis of spectrin were examined in hippocampal slices after periods of hypoxia lasting for 5 or 10 min. The concentration of a approximately 155 kDa BDP increased nearly twofold after 5 min of hypoxia; further increases were not seen with 10 min episodes or 10 min of hypoxia followed by reoxygenation. The hypoxia-induced proteolysis was blocked by prior infusion of a newly introduced inhibitor of calpain (calpain inhibitor I, 200 microM). Together with previously published data showing improved recovery of hippocampal slices from hypoxia in the presence of calpain inhibitors, these data suggest that activation of calpain may contribute significantly to the pathophysiology of ischemia. PMID- 1933342 TI - Decrease of GABA-immunoreactive neurons in the amygdala after electrical kindling in the rat. AB - The present study was designed to investigate the effects of electrical kindling in vivo on GABA immunoreactivity (GABA-IR) of the lateral and basolateral amygdaloid nuclei 2-6 months post-stimulation. Male Sprague-Dawley rats were implanted with bipolar electrodes in the basolateral nucleus and stimulated once per day until 3-5 stage 5 seizures were observed. Coronal sections containing the amygdala were processed for GABA-IR using the contralateral side of the brain. Results indicate that, in comparison to controls, fully kindled animals showed a significant decrease in total number of GABA-IR amygdala neurons. Decreases in GABA-positive punctate structures surrounding unlabeled pyramidal cells were also observed, but not quantified. The present data suggest that epileptogenesis of the amygdala is associated with a significant reduction of GABA-IR in the lateral and basolateral areas throughout the contralateral amygdaloid nucleus. PMID- 1933343 TI - Hippocampal CA1 evoked response and radial 8-arm maze performance after hippocampal kindling. AB - Rats with chronically implanted electrodes in the hippocampal CA1 region were trained in the open radial 8-arm maze and then subjected to kindling (afterdischarges, ADs) or 0.17 Hz low-frequency stimulations (LFSs) as controls. Partial kindling (21 ADs) induced a general increase of AD threshold but no motor convulsions. The commissurally evoked average evoked potentials (AEPs) in CA1 were enhanced above the pre-AD baseline or the AEPs in LFS control rats at 1 day after the 1st, 6th, 11th and 16th AD and for at least 25 days after 21 ADs. Similarly, maze performance was significantly worse in kindled than LFS rats for about 4 weeks after 21 ADs/LFSs. The study confirms the long-lasting behavioral effect of partial kindling and suggests that synaptic enhancement may underlie the behavioral disruption. PMID- 1933344 TI - Effects of reuptake inhibitors on dopamine release from the stalk-median eminence and posterior pituitary in vitro. AB - Similar to other dopaminergic systems, the dopaminergic neurons innervating the stalk-median eminence (SME) and posterior pituitary (PP) possess an uptake mechanism for dopamine (DA). However, the extent of DA reuptake in these tissues and its physiological significance are debated since much of the released DA is removed by the hypophysial portal vasculature before recapture. The objectives of this study were: (1) to establish in vitro conditions for examining the effects of reuptake inhibitors on DA release from the PP and SME; (2) to compare the effects of nomifensine, diclofensine and amphetamine on DA release from the SME and PP; and (3) to distinguish between reuptake and releasing properties of these drugs. Individual SME and PP were dissected from ovariectomized rats and incubated in either a static or perifusion system. Media DA was extracted with alumina and quantitated by high performance liquid chromatography with electrochemical detection. The reuptake inhibitors, nomifensine, dichlofensine and amphetamine, in the presence of pargyline, a monoamine oxidase inhibitor, stimulated both basal and K(+)-evoked release of DA from the SME and PP under static incubation conditions. The drugs elicited a 2-3-fold higher increase in basal DA release from the SME as compared to the PP. Only amphetamine stimulated DA release in the perifusion system whereas nomifensine and diclofensine were without effects. We concluded that: (1) a mechanism for the reuptake of DA is operable in both the SME and PP; (2) the reuptake of DA appears to be more active in the SME than the PP; and (3) unlike amphetamine, nomifensine and diclofensine are pure reuptake inhibitors devoid of direct DA releasing activities. PMID- 1933345 TI - High power, low frequency components of cardiac, renal, splenic and vertebral sympathetic nerve activities are uniformly reduced by spinal cord transection. AB - Others have reported that spinal cord transection non-uniformly affects the activities of the cardiac, renal and splenic nerves. We were unable to confirm this finding while recording the wide band (1-1000 Hz) discharges of these sympathetic nerves in baroreceptor-denervated, chloralose-anesthetized cats. Most of the power in nerve discharges was below 6 Hz. There was high coherence between the low frequency discharges of different nerves, and power below 15 Hz was essentially eliminated by spinal transection. Evidence is presented that the disparities between this and past studies are, in part, due to the use of a 30-Hz high-pass filter in the earlier studies. PMID- 1933346 TI - The chick chorioallantoic membrane promotes survival of co-transplanted rat carotid bodies and nodose ganglia. AB - Carotid bodies and nodose ganglia, removed from adult rats, were co-implanted onto the chorioallantois of 6- to 12-day chick embryos. Implants were rapidly vascularized and incorporated into the chorioallantoic membrane, where they survived and grew for up to 12 days. The morphological characteristics of grafted tissues were largely preserved. Regenerating axons from nodose neurons invaded the carotid body and contacted some glomus cells through morphologically immature synapses. Thus, the chick chorioallantoic membrane may be a useful substrate to study carotid chemoreceptor-sensory neuron interactions. PMID- 1933347 TI - Responses of cardiovascular neurons in the rostral ventrolateral medulla of the normotensive Wistar Kyoto and spontaneously hypertensive rats to iontophoretic application of angiotensin II. AB - In female pentobarbital-anesthetized Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), changes in spontaneous discharges of cardiovascular neurons in the rostral ventrolateral medulla (RVL) in response to iontophoretic application of angiotensin II (Ang II) were studied and compared. It was found that iontophoretic application of Ang II to RVL increased the spontaneous neuronal activities of 30% of the cardiovascular neurons in both types of rats and that the increase was significantly greater in SHR than in WKY. In both types of rats, there was an increase in arterial blood pressure in response to iontophoretic release of Ang II to RVL. The pressor response was accompanied by tachycardia, which was significantly greater in SHR than in WKY. The present study provides evidence that Ang II acts directly on cardiovascular neurons in RVL, and in SHR, an enhanced sensitivity and responsiveness of the RVL cardiovascular neurons to Ang II may augment the sympathetic outflow from RVL and contribute to the genesis of hypertension. PMID- 1933348 TI - NG-monomethyl-L-arginine co-injection attenuates the thermogenic and hyperthermic effects of E2 prostaglandin microinjection into the anterior hypothalamic preoptic area in rats. AB - Prostaglandin E2 (PGE2) microinjection (25 ng, 250 nl) into the preoptic area of the anterior hypothalamus (POAH) stimulated heat production in brown adipose tissue (BAT) and increased core temperature in urethane-anesthetized rats. These thermogenic and hyperthermic effects were attenuated by co-injection of NG monomethyl-L-arginine (NMMA, 25 micrograms), a competitive inhibitor of nitric oxide (NO) production from L-arginine. Inclusion of L-arginine (50 micrograms), though not D-arginine (50 micrograms) reversed the inhibitory effect of NMMA (25 micrograms) on intra-POAH PGE2-induced increases in interscapular BAT (IBAT) and core temperatures. Intra-POAH injection of NMMA (25 micrograms) or L-arginine (50 micrograms) alone had no effect on IBAT and core temperatures. The results suggest that the effect on thermoregulation induced by action of PGE2 in the POAH is modulated by a local L-arginine-dependent and NMMA-sensitive NO-generating system. PMID- 1933349 TI - Excitatory effects of cholecystokinin octapeptide on rat nodose ganglion cells in vitro. AB - Cholecystokinin octapeptide (CCK-8) applied by pressure evoked in the majority of rat nodose ganglion cells a rapid depolarization associated with a fall of membrane resistance and in a few cells a slow depolarization accompanied by an increase of membrane resistance. The fast depolarizations were increased and decreased by membrane hyperpolarization and depolarization; the extrapolated reversal potential was about -10 mV. The response was depressed in a Na-free solution and by d-tubocurarine (10-100 microM) but not in a Cl-deficient solution. It is concluded that CCK-8 depolarized the nodose ganglion cells by increasing cation conductances and in a few cells it also produced a slow excitation, the mechanism of which remains to be established. PMID- 1933350 TI - GABAergic-serotonergic interactions in regulating lordosis. AB - The GABAB agonist, baclofen, causes a dose-dependent decrease in lordosis, and this effect is attenuated following hypothalamic serotonin, (5-HT) lesions. Baclofen administration is associated with decreased 5-HT activity in the medial preoptic (mPOA) and ventromedial nuclei and enhanced 5-HT activity in the midbrain central gray, and with enhanced norepinephrine activity in the mPOA. Interactions between gamma-aminobutyric acid (GABA) and 5-HT may, therefore, be important for the activation of lordosis. PMID- 1933351 TI - Ultrastructure and retinal innervation of deafferentation-induced enkephalin immunoreactive elements in the superficial layers of the rat superior colliculus. AB - Leu-enkephalin-like immunoreactive (ENK-I) elements appearing in the superficial layers of the rat superior colliculus (SC) after eye-enucleation were examined by means of immunoelectronmicroscopy. ENK-I somata were of a single type and formed symmetric and asymmetric synapses with non-immunoreactive axon terminals. Some degenerating retinal terminals made synaptic contacts only with small ENK-I dendrites, suggesting that deafferentation-induced ENK-I neurons in the rat SC receive retinal input onto the distal portions of their dendrites. PMID- 1933352 TI - Characterization of voltage-gated and calcium-activated potassium currents in toadfish saccular hair cells. AB - Patch clamp methods were used to study calcium activated (IKCa) and voltage-gated (IK) potassium currents in enzymatically disassociated hair cells from the saccule of the toadfish Opsanus tau. In one population of hair cells, tetraethylammonium bromide (TEA) blocked all outward current, leaving only an inward calcium current (ICa). This current blocked by TEA was also blocked by barium (5 mM) and cadmium (0.2 mM) but only partially blocked by zero external calcium. In the majority of the cells, after TEA (25 mM) was used to block IKCa, a second outward current remained. This current was resistant to block by apamin, barium (5 mM) and cadmium (0.2 mM). Its kinetics of activation and deactivation were considerably slower than those of IKCa. Because of the current/voltage characteristics, its resistance to block by the above agents and voltage-gated activation, this current was termed IK. Study of the rates of activation and deactivation of the two currents in hair cells exhibiting either fast or slow total outward current activation showed that these two kinetic parameters were linked in a cell, i.e., cells with fast IKCa kinetics exhibit faster IKCa kinetics than cells with slower IKCa kinetics. Cell attached and inside out recordings showed a high conductance channel with short open times and a lower conductance channel with longer open times active over the same voltage ranges as those seen in whole cell recordings. Since these two currents with quite different but linked kinetics are active over the same voltage range, their co existence may be of some importance to sensory coding in the hair cells. PMID- 1933353 TI - In vivo acetylcholine release as measured by microdialysis is unaltered in the hippocampus of cognitively impaired aged rats with degenerative changes in the basal forebrain. AB - Acetylcholine (ACh) release was studied in awake, freely moving animals using in vivo microdialysis in the hippocampus of young (3-month-old) and aged (24-month old) female Sprague-Dawley rats. Two groups of aged rats were selected on basis of their spatial learning performance in the Morris water maze: non-impaired aged rats which performed as well as the young control animals, and impaired aged rats which learnt the task very poorly. Baseline ACh overflow (in the presence of 5 microM neostigmine) was 1.9 +/- 0.3 +/- pmol/15 min in the young animals and 1.6 +/- 0.4 pmol/15 min in both the impaired and the non-impaired aged rats; these levels did not differ from each other. Depolarization by KCl (100 mM) or muscarinic receptor blockade by atropine (3 microM) added to the perfusion fluid produced dramatic, 4-6-fold, increases in ACh overflow that was similar in magnitude in both the young and the aged impaired and non-impaired rats. Behavioral activation by either handling or electrical stimulation of the lateral habenula produced 2-3-fold increases in extracellular ACh-levels in the hippocampus similarly in all three groups. The results indicate that hippocampal ACh release is maintained in aged rats that exhibit severe spatial learning and memory impairments and that the septo-hippocampal cholinergic system retains its capacity to increase its ACh release in response to both K(+)-induced depolarization and behavioral activation in the aged rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933354 TI - Properties of the descending limb of the spinobulbospinal micturition reflex pathway in the cat. AB - The micturition reflex is thought to be mediated by a spinobulbospinal reflex pathway passing through the rostral pons. This study examined the properties of the descending limb of the reflex pathway by monitoring the responses of the lower urinary tract to stimulation of the pons in the decerebrate cat. Electrical stimulation (300 microseconds pulses at 50 Hz intratrain frequencies, 300-500 ms trains, 0.5-15 V) in the region of the locus coeruleus (P 0.5-3.1/L 2-4/H to 2.75) was used to activate the descending excitatory pathway to the sacral parasympathetic nucleus. Low intensity stimulation induced small amplitude, short duration (14 +/- 11 cm H2O, 10 +/- 3 s) bladder contractions in a partially full bladder, whereas higher intensity stimulation induced large amplitude, long duration (69 +/- 29 cm H2O, 70 +/- 44 s) contractions which were similar to distension-induced reflex micturition contractions. The evoked bladder contractions coincided with a reduction in external urethral sphincter (EUS) EMG activity. Following bilateral L7-S3 dorsal root transection, electrical stimulation of the pons still elicited the small amplitude bladder contractions, but the larger amplitude, long duration micturition contractions were abolished. During these small evoked bladder contractions, a suppression of EUS activity still occurred following deafferentation, indicating a pontine mediated bladder/EUS synergy. It is concluded that the pons can initiate bladder contractions and coordinated bladder-sphincter activity, but that afferent feedback (via the dorsal roots) is needed to maintain the large amplitude micturition contractions. PMID- 1933355 TI - Elevation and clearance of extracellular K+ following contusion of the rat spinal cord. AB - The elevation and clearance of extracellular potassium following a standard contusion injury was studied in the thoracic spinal cord of rats. Animals were anesthetized, paralyzed, laminectomized at T9-T11, then artificially ventilated. A 10-g rod was released 5.0 cm above the cord with the dura intact. After impact, the dura-arachnoid and pial membranes were incised to allow penetration of K(+) selective microelectrodes. Electrodes utilized a valinomycin ionophore and were double-barreled, with tip diameters of 3-5 microns. Extracellular potassium activity ([K+]o) increased with the depth of penetration. The maximum values of [K+]o occurred at depths greater than 500 microns, and remained so with time after injury. These data indicate that a dorsal-ventral gradient of [K+]o develops in spinal cords contused from the dorsal surface, with the greatest elevation of [K+]o in the gray matter. In 8 preparations, the maximum [K+]o was 65 +/- 8 mM (mean +/- S.E.M.) at 5 +/- 1 min after injury. The [K+]o peak values decayed with a half-time of 11.0 +/- 3.4 min. Compared with data available for the injured cat spinal cord, the peak [K+]o recovered relatively rapidly. Although a simple diffusion model could account for the rapid clearance of [K+]o, the persistence of dorsal-ventral [K+]o gradients could not be explained by such a model. It is postulated that secondary injury processes contributed to the persistent [K+]o gradients. PMID- 1933356 TI - Nociceptive quality of the orbicularis oculi reflexes as evaluated by distinct opiate- and benzodiazepine-induced changes in man. AB - The corneal reflex and the three components of the blink reflex (R1, R2, and R3) were recorded electromyographically in volunteers. The area of these responses was measured before and after administration of the narcotic-analgesic fentanyl (1.5 mg i.m.) and its antagonist naloxone, and after administration of the benzodiazepine diazepam (10 mg i.v.) and its antagonist flumazenil. Saline was given as a control placebo. The corneal reflex was 71% reduced by fentanyl, 43% by diazepam. R1 was 35% reduced and R2 was 60% reduced by diazepam. R3 was abolished by both drugs. Whereas the fentanyl-induced changes were completely reversed by naloxone, the diazepam-induced changes were only partly reversed by flumazenil. The corneal reflex appears to be a 'nociceptive' reflex under all points of view. Recording of the orbicularis oculi reflexes in man may be valuable in the evaluation of central-acting neurotropic drugs. PMID- 1933357 TI - Kindling-induced potentiation in the piriform cortex. AB - At intensities sufficient to induce epileptiform afterdischarges, repeated electrical stimulation of limbic structures can lead to the development of permanent increases in the strength of the epileptiform response (kindling). Field potentials evoked by pulse stimulation are also increased in amplitude in a number of forebrain pathways following kindling. This kindling-induced potentiation effect is similar in many respects to the 'long-term potentiation' (LTP) effect which is produced by non-epileptogenic stimulation. There are, however, some interesting differences. For example, kindling-induced potentiation can far outlast LTP. In these experiments, we attempted to determine the longevity of the kindling-induced potentiation of the response evoked in the piriform cortex by olfactory bulb stimulation, following olfactory bulb kindling. This system was targeted because both the olfactory bulb and the piriform cortex are highly reactive kindling sites. In addition, we used the paired pulse technique to monitor facilitation and inhibition in this system. Kindling was found to induce a potentiation in the piriform field potential that lasted for at least 3 months (the period of the experiment) with little or no decay. Kindling also produced a decrease in paired pulse facilitation. In some animals the net facilitation was changed to a net depression. These results are consistent with the interpretation that kindling produces an increase in recurrent inhibition in the piriform cortex. The paired pulse measures, however, returned to near baseline levels over the 3-month test period. PMID- 1933358 TI - Different effects of chronic K+ depletion on forebrain and peripheral angiotensin II receptors in young rats. AB - K+ depletion stimulates the circulating renin-angiotensin system and affects the regulation of peripheral angiotensin II receptors. The effects of K+ depletion on the regulation of central angiotensin II receptors are unknown. We studied the effects of selective K+ depletion (less than 0.05% in diet for 16 days) on angiotensin II receptor number in kidneys, adrenal glands, and selected brain areas of young rats. K+ depletion caused a significant increase in plasma renin activity and significantly decreased angiotensin II receptor number in the kidney glomeruli and medulla, and in the adrenal zona glomerulosa and adrenal medulla. In the brain, the angiotensin II receptor number was unchanged in the subfornical organ and the hypothalamic paraventricular nucleus after 16 days of K+ depletion. An additional NaCl supplementation (0.02% in the drinking water) to K(+)-depleted rats produced a decrease in plasma renin activity but failed to affect subfornical organ or paraventricular angiotensin II receptor number. Our results suggest that in young animals, K+ depletion has a significant impact on the peripheral renin-angiotensin system without affecting the density of forebrain angiotensin II receptors. PMID- 1933359 TI - Perforated and non-perforated synapses in rat neocortex: three-dimensional reconstructions. AB - Perforated and non-perforated synapses in the molecular layer of rat parietal cortex have been assessed morphologically and quantitatively using three dimensional reconstructions of the postsynaptic terminal. Perforated synapses were analyzed at nine ages, ranging from 0.5 to 22 months of age, and non perforated synapses at three ages--0.5, 12, and 22 months. Examination of the reconstructions shows that perforated synapses increase in size and complexity with increasing age. This increasing complexity is reflected in a break-up of the postsynaptic density, which is punctuated by larger, branched perforations. In the most extreme cases the result is the appearance of isolated islands of postsynaptic density separated by, and also surrounded by, a synaptic contact zone. Spinules are especially prominent at around 12 months of age in perforated synapses, and the overall negative curvature of the young junctions is replaced by positively curved junctions from 4 months onwards. The non-perforated synapses are relatively small and show few changes with increasing age. Using the measurement option in the reconstruction program, the following trends emerged. All parameters of perforated synapses increased in size with increasing age, whereas the corresponding parameters of non-perforated synapses remained relatively unchanged over this age range. In addition, the percentage of the synaptic contact zone surface area occupied by the postsynaptic density decreased with increasing age in perforated synapses, but increased in non-perforated synapses. The total postsynaptic density surface area of non-perforated synapses per unit volume of molecular layer was double that of perforated synapses at 0.5 months, but the situation was reversed at 12 months. This parameter was similar in the 2 populations at 22 months. This suggests that perforated synapses contribute more to the total surface area of the postsynaptic density in mid- to late-adulthood than do non-perforated synapses, despite non-perforated synapses outnumbering perforated by 2-3:1 at these ages. These data provide more specific evidence that perforated and non-perforated synapses constitute separate synaptic populations from early in development, and that perforated synapses are responsible for the maintenance of neuronal postsynaptic density surface area from mid-adulthood onwards. PMID- 1933360 TI - Developmental immunohistochemistry of catalase in the human brain. AB - The immunohistochemical studies on a peroxisomal enzyme, catalase, were done on brains from human fetuses to adults. The catalase-positive neurons appeared in the basal ganglia, thalamus and cerebellum at 27-28 weeks of gestation, and in the frontal cortex at 35 weeks. They then increased in number with gestational age. The extent of immunopositive staining increased with enlargement of perikaryonal size. However, the extent gradually decreased with postnatal age. On the other hand, catalase-positive glia appeared in the deep white matter at 31-32 weeks of gestation, their appearance shifting from the deep to the superficial white matter with increasing age. These results suggest that peroxisomes are closely related to neuronal growth and myelinogenesis in the human brain during development. PMID- 1933362 TI - Response properties of gerbil otolith afferents to small angle pitch and roll tilts. AB - The responses from isolated single otolith afferent fibers were obtained to small angle sinusoidal pitch and roll tilts in anesthetized gerbils. The stimulus directions that produced the maximum (response vector) and minimum response sensitivities were determined for each otolith afferent, with response vectors for the units being spread throughout the horizontal plane, similar to those reported for other species. A breadth of tuning measure was derived, with narrowly tuned neurons responding maximally to stimulation in one direction and minimally along an orthogonal ('null') direction. Most (approximately 80%) otolith afferents are narrowly tuned, however, some fibers were broadly tuned responding significantly to stimulations in any direction in the horizontal plane. The number of broadly tuned otolith afferents (approximately 20%) differs significantly from the more substantial number of broadly tuned vestibular nuclei neurons (88%) recently reported in rats. PMID- 1933361 TI - Long-lasting effect of ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile. AB - In a model of dyskinesia induced by the administration of iminodipropionitrile (IDPN) in the rat, we evaluated the effects of ceruletide, an analogue of cholecystokinin, on behavioral abnormalities and monoaminergic neuronal function. Vertical head twitching in the IDPN-treated animals was inhibited for over 5 h following a single subcutaneous dose of 160 micrograms/kg ceruletide. In animals dosed daily for 2 or 3 days, the number of head twitches at 24 h after the last dose was about one-third of the number before treatment. After repeated daily doses of ceruletide for 6 days, the number of head twitches was reduced to low levels and remained significantly below pretreatment levels until the 4th posttreatment day. These results indicate that the inhibition of dyskinesia by ceruletide was long-lasting. Assays of monoaminergic neurotransmitters and their metabolites in various brain regions indicate that an imbalance between dopaminergic and serotonergic neuronal systems plays a major role in the pathogenesis of the IDPN-induced dyskinesia, i.e. the ratio of (DOPAC+HVA)/5-HIAA was significantly greater in the striatum but significantly smaller in the hippocampus of the IDPN-treated vs normal animals. This initially abnormal ratio of (DOPAC+HVA)/5-HIAA in the striatum and hippocampus of IDPN-treated animals returned to normal following treatment with ceruletide, corresponding with the reduction of the head twitching. The alterations in monoaminergic neuronal function induced by repeated administration of ceruletide persisted for at least 3 days, even though its plasma half-life is several minutes. Ceruletide also exerted a marked effect on monoaminergic neuronal function in the IDPN-treated rats, in contrast to only a slight effect in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933363 TI - Selective involvement of the spinal trigeminal nucleus in the conditioned nictitating membrane reflex of the rabbit. AB - These experiments were performed to test the hypothesis that a region associated with the trigeminal nuclear complex is selectively involved in mediating the classically conditioned nictitating membrane reflex in the rabbit. Microinjections of Lidocaine were used to produce a temporary, localized block of neural activity following the conditioning of the reflex using a standard tone/air puff-paired stimulus paradigm. Data indicate that the injection of Lidocaine at the medial pars oralis/reticular formation junction results in a selective suppression of the conditioned reflex. PMID- 1933364 TI - Ovarian steroid modulation of [3H]muscimol binding in the spinal cord of the rat. AB - [3H]Muscimol binding was measured in the lumbar spinal cord of female rats by in vitro quantitative autoradiography. Ovariectomized rats were treated subcutaneously with either oil, estradiol benzoate (EB) or EB plus progesterone (P) in a regime known to reliably induce sexual receptivity. The level of [3H]muscimol binding was highest in laminae I-III and in the region around the central canal. Binding was lower in laminae IV-VI and was frequently undetectable in the ventral horn. There was a significant increase in the level of binding in laminae I-III after EB treatment. There was also a significant increase after treatment with EB+P in comparison to both the ovariectomized and EB-treated groups in this same region of the spinal cord. PMID- 1933365 TI - The role of pacemaker properties and synaptic input in generation and modulation of spiking activity in a pair of electrically coupled peptidergic neurons. AB - The origin of patterned electrical activity in two electronically coupled peptidergic neurons, VD1 and RPD2, in the CNS of Lymnaea stagnalis was investigated. VD1 proved to have intrinsic beating pacemaker properties. Hybrid current/voltage clamp experiments demonstrated that in the intact CNS generation of spike activity in the coupled cell system is dominated by VD1. Modulation of spiking activity of VD1/RPD2 appears to originate mainly from chemical synaptic input. The electrical coupling of VD1 and RPD2 proved essential for spike synchronization between the cells. PMID- 1933366 TI - Collateral sprouting of serotonergic fibers in the cingulate cortex and the septum following cortical-hippocampal lesions. AB - The parietal cortex and dorsal hippocampus of adult rats were unilaterally ablated. One and 3 months after this operation, changes in serotonergic fiber distribution in the forebrain were studied immunohistochemically. At 1 month, increased numbers of serotonergic fibers were seen in the cingulate cortex and the medial and lateral septal nuclei of the lesioned side. This increase continued to 3 months in the ipsilateral cingulate cortex. In the present study, two different processes of serotonergic fiber collateral sprouting were noted. Plastic changes in serotonergic fibers in the ipsilateral septal nuclei and cingulate cortex may be attributable to the collateral sprouting underlying reactive synaptogenesis and the pruning effect, respectively. PMID- 1933367 TI - Effects of relative hypoxia and hypercapnia on intracellular pH and membrane potential of cultured carotid body glomus cells. AB - Clusters of glomus cells, isolated from rat carotid bodies, were cultured for up to 2 weeks. Afterwards, we simultaneously measured the intracellular pH (pHi) and membrane potentials (Em) of single cells with pH-sensitive and KCl-filled microelectrodes. In 89 control cells (bathed in saline equilibrated with 50% O2 in N2) pHi was 6.87 +/- 0.014 (SE) and Em -36.3 +/- 0.45 mV. In 42 cells, switching to air (about 20% O2) lowered pHi in 60% of them by as much as 0.14 unit (mean decrease, 0.05). In the remaining cells, pHi increased by as much as 0.18 unit (mean increase, 0.06). Application of 2.5% CO2 in 50% O2 (balance N2) reduced the pHi in 90% of 47 cells by as much as 0.44 unit (mean decrease, 0.14). pHi increased to a maximum of 0.05 unit (mean increase, 0.04) in the others. Either stimulus depolarized or hyperpolarized glomus cells (-5 to 8 mV) in approximately equal proportions. There was a significant and positive correlation between delta Em and delta pHi. This observation confirms the idea that the Em of glomus cell is H(+)-dependent. Results do not agree with the acidic hypothesis for chemoreception. PMID- 1933368 TI - von Recklinghausen neurofibroma produces neuronal and glial growth-modulating factors. AB - Two kinds of novel neural trophic factors were currently detected in von Recklinghausen neurofibroma (NF1) extracts. One of the two was a growth factor, neuroblastoma growth factor (Mr less than 5 kDa), which promotes the proliferation of human neuroblastoma cell and survival and neurite-extension of rat cortical neurons, but differently from nerve growth factor (NGF) or NGF-like factors. The other one was a glial growth inhibitor (Mr = 100 kDa), which suppresses the growth of glioma cell lines, astrocytoma, glioblastoma, oligodendroglioma and Schwannoma. These factors do not appear to be previously identified cytokines or growth factors such as interleukins, granulocyte colony stimulating factor, NGF and fibroblast growth factor. There was also detectable ciliary neurotrophic factor-like activity in the extracts. The primary cause of high contents of these factors in NF1 is not known, but may relate to fundamental mechanisms controlling growth and differentiation of neurons and glias during development of nervous system. PMID- 1933369 TI - Neostriatal dopaminergic terminals prevent the GABAergic involvement in the mu- and delta-opioid inhibition of KCl-evoked endogenous acetylcholine release. AB - Endogenous acetylcholine (ACh) release from rat neostriatal slices was inhibited by the mu-opioid agonist [D-Ala2,Gly(ol)5]-enkephalin (DAGO) both in 6 hydroxydopamine (6-OHDA)-lesioned and non-lesioned neostriatum. However, the delta-opioid agonist [D-Pen2,D-Pen5]-enkephalin (DPDPE) could not inhibit KCl evoked ACh release in the 6-OHDA-lesioned striatum. This result suggests that delta-opioid agonists act on dopaminergic terminals to inhibit the cholinergic neurons. In unlesioned rats, GABAA or GABAB) antagonists (bicuculline or phaclofen, respectively) prevented mu- or delta-opioid inhibition of endogenous ACh release evoked by glutamate, but not by potassium. However, in the 6-OHDA lesioned side, DAGO inhibition of KCl-evoked ACh release was antagonized by either of the GABA antagonists. Our results suggest that the dopaminergic neurotransmission, favored by KCl, blocks the GABAergic involvement in the mu- and delta-opioid inhibition of endogenous ACh release. PMID- 1933370 TI - Chronic exposure to alcohol during development alters the membrane properties of cerebellar Purkinje neurons in culture. AB - The active and passive membrane properties of developing Purkinje neurons in control cultures and cultures chronically treated with 20 or 40 mM ethanol for 1 or 2 weeks were examined using whole-cell current-clamp techniques. The membrane properties were characterized by the features of the voltage responses evoked by intracellular current injection of a series of depolarizing and hyperpolarizing current pulses. Analysis of these responses and background spontaneous activity showed several differences between the control and ethanol-treated Purkinje neurons: (1) membrane input resistance was significantly larger in the ethanol treated neurons; (2) the percentage of neurons exhibiting immature firing patterns was significantly higher in the ethanol-treated neurons; (3) the afterhyperpolarization following a current-evoked train of action potentials was significantly larger in the ethanol-treated neurons; (4) spontaneous activity (synaptic potentials and synaptically evoked spike events) was significantly reduced in neurons treated with 40 mM ethanol for 1 week; spontaneous activity in neurons treated with 20 mM ethanol for 1 or 2 weeks was similar to that observed in the control group. These differences indicate that ethanol exposure during development directly alters the physiological properties of this CNS neuronal type. These neuronal actions of ethanol may contribute to the behavioral deficits observed in animals models of fetal alcohol syndrome. Similar target sites of ethanol action are likely to be present in the human CNS neurons and may be involved in human fetal alcohol syndrome. PMID- 1933371 TI - Differential isolation of eosinophils and myelin phagocytes from mouse peripheral nerves during Wallerian degeneration by uncoated and immunoglobulin-coated sheep red blood cells. AB - Highly purified (less than 95%) eosinophilic granulocytes and myelin phagocytosing macrophages were isolated from enzyme digested mouse peripheral nervous tissue undergoing Wallerian degeneration by sequential centrifugation on Ficoll-Hypaque together with uncoated and immunoglobulin-coated sheep red blood cells. Isolation of eosinophils is a first step for further investigation of the role of these cells during Wallerian degeneration. Myelin phagocytes were found in the Fc receptor positive cell population, while undigested myelin and Schwann cells remained in the interphase. PMID- 1933372 TI - Dextromethorphan protects against the neurotoxic effects of p-chloroamphetamine in rats. AB - Dextromethorphan, an agent that blocks the neuronal-damaging effects of hypoxemia in vitro, was tested for its ability to prevent the neurotoxic effects of p chloroamphetamine (PCA). Rats were treated with either saline, PCA, dextromethorphan, or the combination of PCA and increasing doses of dextromethorphan. Dextromethorphan provided a dose-related protection against the serotonin (5-HT)-depleting effects of PCA. These observations may offer a clue as to the mechanism responsible for PCA-induced neurotoxicity. PMID- 1933373 TI - The effects of central norepinephrine infusions on drinking behavior induced by angiotensin after 6-hydroxydopamine injections into the anteroventral region of the third ventricle (AV3V). AB - Adult male Sprague-Dawley rats were injected with either 6-hydroxydopamine (6 OHDA) or vehicle in the median preoptic nucleus and the organum vasculosum of the lamina terminalis. The subjects were tested for drinking responses to intraventricular angiotensin II (ANG II) or saline during either saline or norepinephrine intraventricular infusions. Rats injected with 6-OHDA into the ventral lamina terminalis initially failed to show drinking responses to ANG II injections. However, norepinephrine infusion in combination with ANG II injection restored the drinking response to ANG II in rats with catecholamine depletions of the lamina terminalis region. PMID- 1933374 TI - Establishment of a monoclonal antibody directed to the minor novel gangliosides in bovine brain and cultured neural cell lines. AB - We established a MAb N-25 reacted with a minor unknown antigen (AgX) in a commercially available GQ1b sample. It also recognized minor antigens in bovine brain (X-1, 2, 3, 4 and 5) and cultured neural cell lines (X-1). AgX is identical to X-5. X-5 is sialidase sensitive and has the common structure as X-1, which is resorcinol positive. These results suggested that novel gangliosides exist in bovine brain and neural cell lines. PMID- 1933376 TI - Acute amphetamine-induced subsensitivity of A10 dopamine autoreceptors in vitro. AB - Extracellular recordings were obtained from spontaneously active, presumed dopamine (DA) neurons of the ventral tegmental area (VTA) of the rat in a slice preparation. Bath-applied (+)-amphetamine (AMPH) (1-30 microM) induced a concentration-dependent decrease in the firing rate of these neurons, which tended to saturate with the highest concentrations used (n = 11). This inhibitory effect was dependent on the activation of D2 receptors since it was reversed by the D2 antagonist sulpiride (n = 8). However, the most striking effect of AMPH was the induction of a prominent subsensitivity of DA autoreceptors: whereas in 18 out of 20 control neurons, the D2 agonist BHT 920 (100 nM) produced a rapid and complete inhibition of the firing, this was observed in none out of 11 neurons 10 min after the end of the application of AMPH (1-30 microM) (P less than 0.001). In these cells, the mean percent inhibition produced by BHT 920 was only 47 +/- 8%. This subsensitivity remained unchanged after 20 min and declined after one hour. This effect was specific, since the sensitivity of GABAB receptors to baclofen (500 nM-1 microM) was not modified by the application of AMPH (n = 12). These results suggest that AMPH-induced DA autoreceptor subsensitivity can be produced acutely and may be the first step in a cascade of events leading to behavioral sensitization to this compound. PMID- 1933375 TI - Power spectral analysis of the baroreflex in neonatal swine. AB - The baroreflex was observed in neonatal swine as young as 4 h of age. Bolus injections of Na nitroprusside (NP) and phenylephrine (PE), induced changes in blood pressure and elicited changes in both heart rate and in cervical sympathetic and splanchnic discharge; changes in sympathetic discharge were reflected in altered power spectral magnitude. Measures of heart rate showed that the magnitude of the PE-induced decreases was positively correlated with increasing postnatal age. The results indicate that the baroreflex, as indicated by changes in sympathetic discharge and heart rate, is present in early neonatal swine. PMID- 1933377 TI - Synaptic potentiation in the hippocampal CA1 region induced by application of N methyl-D-aspartate. AB - The effect of local pressure application of N-methyl-D-aspartate (NMDA) in the synaptic layer of CA1 pyramidal cells was investigated in the guinea pig hippocampal slice preparation using extracellular recording technique. Application of NMDA produced a transient depression and a subsequent 30-60 min potentiation of the field excitatory postsynaptic potential (EPSP) seen as an increase of the initial slope and amplitude of the EPSP. The increase in amplitude was consistently greater than that of the initial slope. Prior tetanization that caused saturation of long-term potentiation prevented the generation of an NMDA-induced potentiation of the initial slope for more than 1-2 h, but not the generation of an increase of the amplitude. PMID- 1933378 TI - Lithium reduces ocular dominance plasticity in kitten visual cortex. AB - Activity-dependent processes within the visual pathway play a crucial role in the expression of ocular dominance plasticity in immature visual cortex. The necessity of non-retinal, modulatory afferents to the regulation of ocular dominance plasticity has been recognized. Among a few chemically defined signaling systems, the noradrenaline-activated beta-adrenoreceptors seem to have a prime role in this matter. The involvement of acetylcholine afferents was also proven. We looked for plausible molecular mechanisms which integrate the contribution of the two neuromodulator systems to ocular dominance plasticity. At the first step, based on the rich literature on psychotropic action of lithium and the recent advancement in understanding of its molecular mechanisms, we physiologically studied visual cortex of kittens which had been repeatedly injected with the lithium solution intraperitoneally or the cortex directly infused with it. We found (1) that ocular dominance plasticity was significantly reduced in lithium-injected kittens, (2) that the decrease was directly correlated with plasma concentrations of lithium (i.e. the higher the lithium concentration, the lower the plasticity), and (3) that the comparable decrease in the plasticity was obtained from kitten visual cortex which had been directly infused with the lithium solution. The present results suggest that lithium sensitive processes, through most likely reduced production of second messengers, underlie the regulation of ocular dominance plasticity. PMID- 1933379 TI - Delayed application of MK-801 attenuates development of morphine tolerance in rats. AB - To investigate the possible involvement of enduring or delayed changes at the N methyl-D-aspartic acid (NMDA) receptor in the mechanisms of morphine tolerance, rats were treated with the specific NMDA receptor antagonist, MK-801 (0.15 mg/kg) 2 h after morphine injection (20 mg/kg) during a 4-day induction period of tolerance. On the fifth day rats were injected only with morphine (15 mg/kg), and analgesia was assessed using the hot-plate test. Morphine tolerance was significantly reduced by MK-801. These findings suggest that long-lasting or delayed changes at the NMDA receptor underlie the development of morphine tolerance. Moreover, because MK-801 was delivered 2 h after morphine and therefore could not serve as a cue for morphine administration, these findings indicate that the attenuating effect of MK-801 on the development of morphine tolerance is not attributable to state-dependent learning. PMID- 1933380 TI - Electrophysiological evidence for hypothalamic defense area input to cells in the lateral tegmental field of the medulla of rabbits. AB - Single cell recordings were made from neurons in the lateral tegmental field of the medulla (LTFM) during electrical stimulation of the hypothalamic defense area (HDA) of the rabbit. Fifty-four cells were inhibited by HDA stimulation; 23 of these cells received barosensory input. Twenty-two LTFM cells showed an increase in firing rate during HDA stimulation; 10 of these cells received barosensory input. The results of this study provide evidence that the hypothalamic defense area makes functional connections with cardiovascular-influenced neurons in the LTFM. PMID- 1933381 TI - Neurochemical changes associated with the persistence of spontaneous oral dyskinesia in rats following chronic reserpine treatment. AB - Rats treated chronically with reserpine develop spontaneous oral dyskinesia. The present study examined the development of the oral dyskinesia during the course of reserpine treatment, and its persistence after termination of treatment. Rats were injected with either reserpine (1 mg/kg, s.c.) or vehicle once daily for 4 days and then every other day for 6 weeks. Oral dyskinesia developed rapidly, reaching a maximal level after 3 days. It persisted at a maximal level for up to 20 days after termination of reserpine treatment, and continued to persist above control level for at least 60 days. The reserpine-treated rats also exhibited stereotypy in response to acute injection of the D1-selective agonist SKF-38393 (10 mg/kg), which was not observed in control rats. In contrast to the oral dyskinesia, this altered sensitivity to SKF-38393 returned to normal within 20 days after terminating the reserpine treatment, suggesting that these two behavioral responses involve different neural mechanisms. Quantitative autoradiographic measurement of dopamine receptor subtypes revealed that both D1 and D2 receptors were increased in the caudate-putamen (Cpu) and nucleus accumbens. Only the increase in D2 receptor density in the CPu correlated with the persistence of the oral dyskinesia; both changes persisted following termination of the reserpine treatment, and their magnitude was less at 60 days than at 1 and 20 days post-treatment. These results may have important implications for tardive dyskinesia. PMID- 1933382 TI - Modification by focused ultrasound pulses of electrically evoked responses from an in vitro hippocampal preparation. AB - The application of short pulses of focused ultrasound was studied as a method of modifying electrically evoked responses in the mammalian brain. The in vitro hippocampal preparation was employed to facilitate delivery and dosimetry of ultrasound, and assessment of mechanisms of ultrasound effects. Cellular and dendritic field potential responses evoked by electrical stimulation of the Schaffer/Commissural afferents were examined before, during and after exposure of a portion of the CA1 region to focused ultrasound pulses for periods ranging from 2 to 15 min. Focused ultrasound with a repetition rate of 150 kHz was delivered in pulses comparable in duration to an electrical pulse that could initiate activity in the nervous system. The pulses had a center frequency of 750 kHz, durations of about 6 microseconds, and spatial-peak-temporal-averaged intensities of about 80 W/cm2. These parameters are markedly different from those employed in conventional diagnostic ultrasound. Temperatures in the bath and tissue were monitored. Extracellular field potentials reflecting the presynaptic fiber volley, dendritic response and cellular discharge were significantly reduced by exposure to ultrasound. Recovery occurred to varying degrees, and in one experiment was complete. Average temperature changes observed were less than 1 degree C. The present study demonstrates that the electrically evoked response in mammalian brain can be altered by ultrasound in a non-thermal, non-cavitational mode, and that such effects are potentially reversible. PMID- 1933383 TI - Effects of visceral distension on the activities of neurones receiving cutaneous inputs in the rat lumbar dorsal horn; comparison with effects of remote noxious somatic stimuli. AB - (1) Unitary extracellular recordings were made from 92 lumbar dorsal horn neurones in urethane-anaesthetised rats. These neurones were classed as 'noxious only' (4), 'non-noxious-only' (33) or 'convergent' (55) by their responses to stimulation of their cutaneous receptive fields on the ipsilateral hindpaw. (2) Distension of abdominal viscera (colon, urinary bladder) depressed the activities of the vast majority (93%) of the convergent neurones but of only one other cell (a non-noxious-only neurone). Similarly, noxious stimulation of widespread somatic structures depressed activity in all but one of the convergent neurones but in only 3 other cells (one non-noxious- and two noxious-only neurones). One or other of these procedures also excited 3 cells--one convergent neurone responding to distension of the colon, another to stimulation of widespread somatic structures and one non-noxious-only neurone being excited by stimulation on the contralateral hindpaw. (3) The inhibitory effects of the noxious somatic stimuli were very like those described previously and termed 'diffuse noxious inhibitory controls' (DNIC) and it seems likely that the effects of the visceral stimuli were also manifestations of DNIC, particularly in view of their similar, nearly total, specificity to convergent neurones. There were however, some small differences in the extent and temporal evolution of the inhibitory effects of the visceral and of the somatic stimuli--the visceral stimuli generally producing weaker inhibitions with slower rates of onset and recovery. It is proposed that these differences may have reflected different amounts and patterns of activity in the relevant primary afferent fibres rather than being due to different central neural mechanisms. (4) These results and the likely explanation that the effects of the visceral stimuli were mediated by a diffuse mechanism should be taken into account when interpreting the results of other studies in which inhibitory effects are produced by visceral stimulation. PMID- 1933384 TI - Transection of the superior cerebellar peduncle interferes with the onset and duration of generalized seizures induced by amygdaloid kindling. AB - We studied the effect of transections at the superior cerebellar peduncle during the evolution of amygdaloid kindling. Dentato- and interposito-thalamic pathways, including the ascending fastigial fibers, were transected in 10 rats at the contralateral side of the stimulated amygdala, and in other 8 at the ipsilateral side. A group of 18 rats was used as control. Contralateral lesion significantly slowed amygdala kindling, while ipsilateral lesion decreased kindled seizure duration. Furthermore, when kindled seizures were reached by 6 control rats, transection of the ipsilateral superior cerebellar peduncle led to reduction of subsequent seizures. These specific effects produced by transection of the superior cerebellar peduncle suggest that the cerebellum could exert a tonic effect over the participating circuitry used by the kindling process. PMID- 1933385 TI - Morphine enhances the activity of thermoreceptive cold-specific lamina I spinothalamic neurons in the cat. AB - The possibility that morphine might differentially affect spinal neurons responsive to small-diameter thermoreceptive-specific afferents was tested. Systemic morphine enhanced a portion or all of the stimulus-response function of 7 of 9 lamina I spinothalamic tract cells specifically sensitive to cold applied to the glabrous hindpaw in the cat. This result contrasts strongly with the predominant inhibition of nociceptive lamina I neurons by morphine. PMID- 1933386 TI - Response of brain protein kinase C isozymes to ethyl oleate, an alcohol metabolite. AB - Rat brain protein kinase C (PKC) isozymes I, II and III were stimulated by fatty acids in the absence and presence of calcium. Ethyl oleate, which by itself has no effect on PKC activity, had a potentiating effect on fatty acid-induced activation of all 3 isozymes. Potentiation was observed predominantly in the presence of calcium. Interaction of ethyl oleate with a signalling mechanism involving PKC may underlie the cognitive disturbances noted after alcohol consumption. PMID- 1933387 TI - Effect of different restraint schedules on the immobility in the forced swim test: modulation by an opiate mechanism. AB - The present research was conducted to evaluate the influence of different stress schedules on behaviors displayed during both phases of the forced swim test (FST). In addition, the involvement of an opiate mechanism in the behavioral consequences of chronic restraint was investigated. Exposure to a single, but not to chronic, restraint event induced an increase in the immobility score obtained during the 10-min initial swimming exposure (initial test) of the FST. Animals submitted to a previous regime of repeated restraint showed a significant increase in immobility during the 5-min second swimming exposure (retest period) of this behavioral task. However, naloxone (NAL) administered before each of the seven restraint events, blocked the higher immobility observed in chronically stressed rats during the retest period suggesting the involvement of an opiate mechanism. Results concerning the effect of chronic stress on the behavior displayed during the FST were discussed with reference to previous reports which have proposed that immobility performed during the retest period of the FST represents an efficient adaptive response in this inescapable aversive experience. PMID- 1933388 TI - Effects of tetrodotoxin on the circadian pacemaker mechanism in suprachiasmatic explants in vitro. AB - Using perifused explants of the rat suprachiasmatic nucleus (SCN), the effects of tetrodotoxin (TTX) on vasopressin (VP) release and its circadian profile were studied at various times throughout the circadian cycle. VP release from SCN explants was consistently attenuated during TTX treatment, with the amplitude of this effect depending on the time of administration. In addition, the effect of TTX on the circadian pattern of VP release was also time-dependent, such that treatment during the late subjective day was followed by a disruption of circadian rhythmicity in which peptide output remained at basal levels without notable variation whereas treatment at all other times caused no measurable perturbation in the circadian VP rhythm in succeeding cycles. In SCN explants experiencing this TTX-induced arrest of circadian VP output, subsequent exposure to KCl induced acute increases in VP release, suggesting that VP neurons retain the capacity to actively release peptide in spite of this effect of TTX. These results indicate that the interruption of electrical impulses at a critical phase may compromise the circadian function or output of the pacemaker in the SCN. In addition, the present observations provide further evidence that the overt expression of circadian rhythmicity is dependent on sodium-generated action potentials and that disruption of these electrical signals does not alter the precision of the SCN pacemaker, at least in instances where the phase of the VP rhythm can be determined after treatment. PMID- 1933389 TI - Bicuculline-induced neocortical epileptiform foci and the effects of 6 hydroxydopamine in developing rats. AB - Catecholamines (dopamine and norepinephrine) are considered to be predominantly inhibitory neurotransmitters in the brain and their depletion produced by 6 hydroxydopamine may result in proconvulsant effects. In our experiments on rats aged 5, 7, 9, 12, 15, 18, 25 and 90 days under urethane anesthesia we demonstrated the development of neocortical epileptic focus evoked by topical application of bicuculline methiodide. In experimental groups aged 7, 12, 18, 25 and 90 days a chronic depletion of catecholamines was induced using pretreatment with 6-hydroxydopamine early postnatally. An epileptogenic focus was induced in all age groups; duration of a single discharge decreased with age in both control and experimental animals. The spread of activity from the primary focus to contralateral frontal cortex via callosal connections was as rapid as in controls. However, the transfer of discharge to occipital regions was delayed and the number of discharges decreased in experimental rats. Our study demonstrated a substantial role of catecholamines for synchronization of focal discharges in neocortex and a promoting role of catecholamines in association pathways within neocortex. PMID- 1933390 TI - Morphine and GABA: effects on perception, escape response and long-term habituation to a danger stimulus in the crab Chasmagnathus. AB - Prior results (37) showed that morphine pretreatment reduces the escape response of the crab Chasmagnathus to a shadow passing overhead and prevents the acquisition of a long-term habituation. These results were explained by a reduction in the danger signalled by the stimulus, and to test this hypothesis methods other than morphine injection were used herein to abolish response during training. GABA pretreatment induced a dose-dependent reduction in responsiveness to the danger stimulus, and instances of autotomy were shown with doses larger than 12 micrograms/g. A response was rarely displayed with a 9 micrograms GABA/g dose given 5 min before training, but long-term memory was acquired. In one experiment, both morphine and GABA pretreatment produced similar mild response inhibition during training, but morphine, not GABA impaired long-term habituation. Morphine administered immediately after training had no amnesic effect. These results support the hypothesis that morphine effects may be explained by transient disruption between the stimulus and its danger meaning, ruling out alternative explanations such as response inhibition or amnesia due to either storage or retrieval failure. PMID- 1933391 TI - Long-term behavioral and biochemical effects of 6-hydroxydopamine injections in rat caudate-putamen. AB - Unilateral injections of 6-hydroxydopamine into the rat striatum result in amphetamine-induced circling behavior. This rotational behavior was associated with an almost complete disappearance of desmethylimipramine-insensitive [3H]mazindol binding sites--which represent dopamine uptake sites-in the ipsilateral caudate-putamen (CPu), the substantia nigra pars compacta (SNpc), and in the ventral tegmental area (VTA). There were significant increases in [3H]spiperone-labeled dopamine (DA) D2 receptors in specific subdivisions of the ipsilateral CPu, with the dorsolateral (DL) and ventrolateral (VL) regions showing significant increases in DA D2 receptors. There were nonsignificant increases in the dorsomedial (DM) aspects of the ipsilateral CPu whereas there were no changes in the ventromedial (VM) aspects of that structure. In contrast, there were no significant changes in [3H]SCH 23390-labeled DA D1 receptors in any of the subdivisions of the CPu ipsilateral to the 6-OHDA-induced lesions. These results provide evidence that intrastriatal injections of 6-OHDA result in biochemical changes in rat brain which are almost identical to those observed after 6-OHDA-induced lesions of the substantia nigra. These long-term biochemical effects caused by intrastriatal 6-OHDA injections provide further support for the idea that the nigral DA cell loss observed in the brains of parkinsonian patients could be secondary to retrograde changes due to oxyradicals generated during the metabolism of catecholamines within the caudate-putamen. PMID- 1933392 TI - Estimation of haloperidol concentrations in rat striatum after chronic treatment. AB - 3H-Spiroperidol association and dissociation rate constants were determined in rat striatal homogenates in the presence of known concentrations of unlabelled haloperidol. The rate of 3H-spiroperidol association was progressively decreased in the presence of increasing concentrations of haloperidol and no changes were seen in 3H-spiroperidol dissociation rate constants. Measuring changes in 3H spiroperidol association rate constants permitted detection of 0.1 pmol/ml unlabelled haloperidol in assay homogenates. Then, male Sprague-Dawley rats received daily injections of haloperidol (1.5 mg/kg) for 1-21 days. Twenty-four hours after the last injection, 3H-spiroperidol kinetic rate constants and Kd values were measured and found to be unchanged in all treatment groups. These findings suggest that, under these conditions of drug withdrawal and tissue preparation, which are widely employed in studies of chronic neuroleptic administration, residual haloperidol does not interfere with the estimation of 3H spiroperidol binding parameters. PMID- 1933393 TI - Neural structures associated with reproductive development and photoperiodic effects in male chicks (Gallus domesticus). AB - White Leghorn chicks given parasagittal knife cuts that isolated the hypothalamus from lateral connections displayed early maturation of the testes. When the operated chicks were subsequently exposed to a long-day photoperiod known to stimulate gonadal development, no additional increase in the size of the testes occurred. In contrast, controls demonstrated a marked development of the gonads that surpassed testes size of experimentals. An additional study was designed to determine whether the archistriatum, a telencephalic structure that has significant projections to the hypothalamus, may be involved in the earlier onset of puberty shown by knife-cut chicks. Three different sets of brain cuts were made that severed projections from the archistriatum to the hypothalamus. None of the knife cuts affected development of the gonads when the birds were examined six weeks after surgery. Two of the three sets of knife cuts, however, effected a significant reduction in food intake, and operated chicks also displayed a significantly lower body weight compared to controls (p less than 0.05). PMID- 1933394 TI - Magnetic auditory M100 source location in normal females. AB - We recorded magnetoencephalographic auditory evoked fields from the left and right hemispheres of six normal adult female subjects, in response to unattended tone pips. Magnetic field data was used to estimate location, orientation, depth, and strength of the 100-ms latency evoked field component (M100). M100 source locations did not significantly differ in left and right hemispheres. Previous studies in six normal males demonstrated M100 sources to be significantly further anterior in the right hemisphere. Compared to the previously reported male subjects, M100 sources in the right hemisphere of these females were significantly further posteriorly, by a mean value of 2.1 cm. These findings, while preliminary, support sex-related functional and/or structural differences in the superior temporal lobe, and would be compatible with the female right temporal planum extending further posteriorly. They suggest MEG recordings may be a useful addition to studies of sex-related difference in brain function and/or structure. PMID- 1933395 TI - Evidence against parenchymal metabolites directly promoting pial arteriolar dilation during cortical spreading depression in rabbits. AB - The role of parenchymal metabolic factors in directly promoting pial arteriolar dilation during cortical spreading depression (CSD) in anesthetized rabbits was examined by direct measurement of periarachnoid cerebrospinal fluid (CSF) levels of a representative metabolite (i.e., K+) or superfusion of the cerebral cortical surface with artificial CSF. CSD was induced by KCl microinjection or tissue puncture and its movement was monitored electrophysiologically. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. CSD propagated across the cortex under the window with a velocity of 2.9 +/- 0.2 mm/min, and caused pial arteriolar diameter to increase from 87 +/- 9 microns to 133 +/- 11 microns (53%, n = 23) for 1.6 +/- 0.1 min. At the same time, K+ concentration increased from 3.0 +/- 0.2 mM to a maximum of 4.6 +/- 0.3 mM. Topical application of 6 mM K+ increased pial arteriolar diameter by only 8%. Continuous superfusion of the cortical surface with aCSF at a rate of 3.0-4.5 ml/min (window volume = 0.5 ml) did not affect pial arteriolar dilation during CSD, but virtually abolished pial arteriolar dilation during inhalation of 10.2% CO2. These results suggest that pial arterioles dilate via a mechanism which does not involve diffusion of vasoactive metabolites released from the parenchyma during CSD. PMID- 1933396 TI - Electrophysiological evidence for axonal degeneration of locus coeruleus neurons following long-term forced running stress. AB - Using electrophysiological methods, a change in the density of axon terminals of locus coeruleus (LC) neurons in the cerebral cortex of rats following long-term forced running stress was examined. The stressed animals were classified into two groups based on spontaneous running activity (SRA) measured for 2 weeks after the stress treatment: 1) animals showing early restoration of SRA (poststress active rat) and 2) animals showing little or no SRA (poststress inactive rat). To quantify the density of LC axon terminals in the cerebral cortex, the percentage of LC neurons antidromically activated by cortical stimulation (projection index, P-index) was assessed. The P-indices for the cortex decreased in the poststress inactive rats. Since the threshold currents for antidromic activation were not altered by the stress treatment, the observed change was considered to reflect a change of the density of LC axon terminals rather than physiological consequences. Therefore, when animals receive a prolonged, severe stress, LC neurons in a certain group of the animals may cause axonal retraction or degeneration in the cerebral cortex. PMID- 1933397 TI - Convergence from the preoptic area and arcuate nucleus to the median eminence in acupuncture and nonacupuncture point stimulation analgesia. AB - Lesion of the preoptic area (POA) or medial arcuate nucleus (M-HARN) abolished acupuncture analgesia (AA). Potentials in the median eminence (ME) evoked by stimulation of the acupuncture point (AP) were not affected by lesion of either the POA or M-HARN alone, but were abolished by concurrent lesion of both. No analgesia was produced by stimulation of the POA. Analgesia produced by stimulation of the M-HARN was abolished by lesion of the POA, and the abolished analgesia was restored by concurrent stimulation of the POA and M-HARN, hence POA and M-HARN outputs might converge in the ME to produce AA. Similar convergence from the anterior arcuate nucleus (A-HARN) and POA to the ME was observed in analgesia (NAA) produced by stimulation of a nonacupuncture point (NAP). Two pathways diverged from the lateral hypothalamus in the AA afferent pathway and two from the lateral periaqueductal central gray (L-PAG) in the NAA afferent pathway. POA potentials evoked by stimulation of the AP were reversed by naloxone, and those evoked by stimulation of the AP were reversed by dexamethasone. ACTH sensitive sites were found in both the L-PAG and the anterior hypothalamus. PMID- 1933398 TI - Organization and development of the cingulum: laminar arrangement of acetylcholinesterase-rich components in rat. AB - The cingulum of the rat is seen to be composed of several distinct fiber and neuronal somal components. In histochemical preparations, three acetylcholinesterase (AChE)-rich fiber zones are noted. The most dorsal originates in the cholinergic cell groups of the basal forebrain, (BF). There is a second, poorly reactive region subjacent to the BF afferent zone. The third, and most ventral zone, has not been described previously. It is operationally dubbed the entocingular fasciculus, ECF. It consists of a moderately dense plexus of AChE-reactive axons and dendrites. In contrast to the regularity and coherence of BF afferents, ECF fibers run in all directions in relation to adjacent cortical (cingulate, sensory-motor), subcortical and transcallosal sites. Knife cut lesions indicate the presence of a substantial proportion of fibers that travel either rostrally or caudally within the ECF itself. The small number of neuronal somata within the cingulum are mostly localized to the ECF. Ultrastructurally, these cells appear to synthesize AChE and form a single type of axo-somatic synapse; synapses are not common in the ECF. Altogether, these observations suggest that the ECF is a conduit for AChE-rich fibers directed towards targets outside of this structure. The AChE reactivity within the ECF first becomes apparent in the second postnatal week, lagging somewhat behind the enzymological maturation of BF afferents. It is concluded that in addition to BF afferents, other AChE-rich fibers travel in the cingulum. A distinctive population of fibers appears to bridge between various cerebral sites via the ECF. These latter observations raise the speculative possibility of a role for the ECF in limbic and sensorimotor cortical interactions. PMID- 1933399 TI - Effects of trazodone and m-chlorophenylpiperazine (m-CPP) on acute dependence in mice. AB - The antidepressant trazodone and its main metabolite, m-CPP, having an antiserotoninergic and serotoninergic activity respectively, were studied in an acute dependence model in mice, to establish whether 5-hydroxytryptaminergic systems are involved in the manifestations of acute opiate dependence and in its development. When drugs were administered 15 min before naloxone, all signs of abstinence decreased, with the exception of teeth chattering that was increased by m-CPP and unaffected by trazodone. When injected 15 min before morphine, jump episodes were decreased by the highest doses of both drugs, while teeth chattering was decreased by m-CPP only. When administered 1 h before morphine, trazodone increased paw and head shakes and mCPP decreased teeth chattering and both left the other signs unaffected. Serotoninergic systems seem to have a significant role in events involved in the withdrawal syndrome and a minor one in those leading to the development of dependence. PMID- 1933401 TI - Protection against hypoxia-induced passive avoidance deficits: interactions between DuP 996 and ketanserin. AB - DuP 996 and ketanserin have previously been shown to protect against experimentally induced passive avoidance (PA) deficits. In the present experiment the potential interaction between DuP 996 and ketanserin on hypoxia-induced amnesia was evaluated. Exposure to hypoxia (6.5% oxygen) produced a reliable deficit in PA retention which was attenuated by posthypoxia treatment with DuP 996 (0.01-0.1 mg/kg SC). Similar effects were found with ketanserin at 1.0 and 3.0 mg/kg SC. Coadministration of ketanserin, at a dose that did not protect against hypoxia (0.3 mg/kg SC), and DuP 996 (at doses of 0.005, 0.1, 0.03, 0.1, 0.3 and 1.0 mg/kg SC) revealed a potentiation of both previously inactive doses of DuP 996 (e.g., 0.005, 0.3, and 1.0 mg/kg SC) and an increase in the protective effect of previously active doses of DuP 996 (0.01, 0.03, 0.1 mg/kg SC). These results suggest that combined administration of DuP 996, a neurotransmitter release enhancer, with ketanserin, a serotonin (5HT) antagonist, may provide a useful treatment for dementia. PMID- 1933400 TI - Cerebrospinal fluid and plasma concentrations of oxytocin and vasopressin during parturition and vaginocervical stimulation in the sheep. AB - Simultaneous blood and cerebrospinal fluid (CSF) samples were taken from conscious sheep before, during and after parturition. Concentrations of plasma and CSF oxytocin were significantly elevated during contractions and particularly at birth. Mean prepartum CSF concentrations of oxytocin were around 55% of those found in plasma but postpartum they were up to 2-fold higher than those in plasma. Plasma concentrations of oxytocin were only significantly elevated, compared to prepartum levels, for 15 min postpartum whereas those in CSF were increased for the whole of the 120 min postpartum sampling period. Plasma, but not CSF, concentrations of arginine-vasopressin (AVP) were significantly raised during contractions and birth, and for 15 min postpartum. During the prepartum period CSF AVP concentrations were 67% of those found in plasma whereas at birth plasma levels were 10-fold higher than in CSF. In a separate experiment it was shown that 5 min of mechanical vaginocervical stimulation also stimulated significant increases in CSF and plasma oxytocin concentrations and in plasma vasopressin. Results support previous work suggesting an important role for central oxytocin release in the postpartum induction of maternal behavior and demonstrate that elevated concentrations of oxytocin in the CSF are present for a greater period than in blood. Elevated plasma AVP concentrations during contractions, birth or vaginocervical stimulation may be stimulated by stress associated with these stimuli. PMID- 1933402 TI - A method for culturing rat oviduct gamma-aminobutyric acid cells. AB - A technique for the culture of rat oviduct gamma-aminobutyric acid (GABA) cells is described. The technique involves first explaining the fimbria and preampulla, which are the oviduct divisions with the highest density of GABA cells. The explanted tissue is cultured in a serum-free medium, to propagate the outgrowing cells. Under the experimental conditions we describe, the majority of the cells maintain GABA expression, as determined by immunostaining with a GABA antiserum. PMID- 1933403 TI - Cytochemical relationships and central terminations of a unique population of primary afferent neurons in rat. AB - Light and electron microscopic immunohistochemical techniques were used to investigate the central projections and colocalization relationships of a subpopulation of primary afferent neurons that were immunolabelled with an antibody (AB893) against rat liver gap junctions. In lumbar dorsal root ganglia AB893-immunoreactivity was seen in 14.5% of all cells and in both small and large size neurons. Colocalization analysis showed that 78% of all AB893-immunoreactive (AB893-IR) neurons contained calcitonin gene-related peptide, while only 7 to 10% contained the calcium binding proteins parvalbumin or calbindin D28k. Among small type B AB893-IR ganglion cells, it was calculated that over 90% contained fluoride-resistant acid phosphatase, while only 1 to 2% contained substance P or somatostatin. Cytochrome oxidase histochemistry revealed light staining in the vast majority of AB893-IR cells. In the dorsal horn of the spinal cord the antibody labelled fibers in the dorsal root, Lissauer's tract, lamina I and lamina II. Isolated immunoreactive fiber bundles were arranged in sheets spanning most of lamina II. Immunoreactive fibers were depleted from the dorsal horn after dorsal rhizotomy or neonatal capsaicin treatment. Ultrastructural examination showed that AB893-IR fibers were composed of closely associated clusters of 2 to 5 unmyelinated fibers each ranging from 0.1-0.4 microns in diameter. Immunoreactivity was distributed intermittently along the cytoplasmic membrane of axons and en passant sinusoid terminals located centrally within the fiber clusters, as well as along axonal membranes adjacent to the central axon or terminal. The results suggest that the immunoreactive fibers in lamina II of the dorsal horn originate from a subpopulation of AB893-IR neurons that contain FRAP and give rise to unmyelinated axons. PMID- 1933404 TI - 1(2-benzoylethyl)pyridinium chloride: a new potent and selective inhibitor of bovine brain and human placental choline acetyltransferase. AB - A newly synthesized 1(2-benzoylethyl)pyridinium (BEP), an analog of the choline acetyltransferase (ChA) inhibitor (2-benzoylethyl)trimethylammonium (BETA), was evaluated for its ability to inhibit ChA from bovine brain and human placenta. Its ChA inhibitory properties were compared with that of BETA. BEP was found to be an effective inhibitor of ChA (I50: 10-18 microM). BEP, as well as BETA, was a linear noncompetitive inhibitor of ChA with respect to both substrates, acetylcoenzyme A and choline. BEP and BETA were poor inhibitors of electric eel acetylcholinesterase. These observations indicate that BEP is a potent and selective inhibitor of ChA. Furthermore, because of the possible delocalization of the positive charge at the N atom of the BEP molecule throughout the pyridine ring, it is anticipated that BEP would have a higher potential for lipid solubility, stability and selectivity than BETA. PMID- 1933405 TI - Amniotic-fluid ingestion enhances the central analgesic effect of morphine. AB - Amniotic fluid and placenta contain a substance (POEF) that when ingested enhances opioid-mediated analgesia produced by several agents (morphine injection, vaginal/cervical stimulation, late pregnancy, footshock), but not that produced by aspirin injection. The present series of experiments employed quaternary naltrexone, an opioid antagonist that does not readily cross the blood brain barrier, in conjunction with either peripheral or central administration of morphine, to determine whether amniotic-fluid ingestion (and therefore POEF ingestion) enhances opioid-mediated analgesia by affecting the central and/or peripheral actions of morphine. The results suggest that POEF affects only the central analgesic effects of morphine. PMID- 1933406 TI - Developmental effects of vitamin B-6 restriction on the locomotor behavior of rats. AB - The nocturnal spontaneous locomotor behavior of vitamin B-6 restricted and control rats was measured using activity chambers. The results show a generalized hypoactivity in indices of horizontal and vertical activity in neonatal rats fed vitamin B-6 restricted diets during gestation and lactation. This pattern of locomotor behavior changed in the postweaning period to a gradual increase in indices of locomotor activity to a pronounced hyperkinesis in vitamin B-6 restricted young adult rats. This study suggests that long-term vitamin B-6 restriction results in damage and/or abnormal development of neuronal system(s) associated with locomotor behavior. PMID- 1933407 TI - Characterization of a synaptosomal ATP diphosphohydrolase from the electric organ of Torpedo marmorata. AB - A true ecto-apyrase (ATP diphosphohydrolase, EC 3.6.1.5) enzyme was found in the synaptosomal fraction from the electric organ of the electric ray Torpedo marmorata. The activity could not be attributed to the combined action of different enzymes. The pH requirement and calcium dependence were the same for hydrolysis of both substrates ADP and ATP. The enzyme had an apparent Km value of 117 microM for ATP and of 123 microM for ADP. The involvement of nonspecific phosphatases in the hydrolysis of both substrates was excluded. The enzyme hydrolyses almost equally well different nucleoside di- and triphosphates. ATP and ADP hydrolysis was not inhibited by seven ATPase inhibitors, i.e., sodium azide, dinitrophenol, ruthenium red, oligomycin, ouabain, sodium orthovanadate and lanthanum. PMID- 1933409 TI - Distribution of GABA immunoreactive systems in the forebrain and midbrain of the chameleon. AB - An immunocytochemical method, using glutaraldehyde fixation and an antiserum developed against a GABA-glutaraldehyde protein conjugate, permitted direct visualization of GABAergic structures in the brain of a reptile (chameleon). GABA immunoreactive cell bodies and nerve terminals were observed to be evenly distributed throughout the forebrain and midbrain. In the forebrain, GABA positive perikarya were shown in all cortical areas, the septal area, the striatum, the dorsal ventricular ridge, and in the nucleus accumbens. In the midbrain, the optic tectum contained a dense and laminar distribution of GABA neurons. These neurons were also observed in the lateral geniculate nucleus, nucleus profundus mesencephali, nucleus opticus tegmenti and substantia nigra. Immunoreactive nerve fibers and terminals were observed in the same structures and, additionally, in the tractus septo-hypothalamicus, habenula complex, median eminence, intermediate lobe of the pituitary, basal part of the subcommissural organ, torus semicircularis and nucleus reticularis isthmi. These results provide a framework for a further electron microscopic analysis of the GABAergic innervation of some encephalic areas involved in physiological regulations particular to this species especially the visual system. PMID- 1933408 TI - Ventral tegmental lesions impair sexual receptivity in female hamsters. AB - The ventral mesencephalon appears to be one of the sites of progesterone action in the control of sexual receptivity in female hamsters. The behavioral response to systemic progesterone was assessed in female hamsters following electrolytic lesions of portions of the ventral mesencephalon. Adult female hamsters were ovariectomized and pretested for sexual receptivity, then were given bilateral lesions aimed at the region of the ventral mesencephalon where progesterone implants have been shown to facilitate receptivity. Lesions were produced by stereotaxically lowering an electrode and applying anodal direct current of 1-2 mA for 5-20 seconds. One week later the hamsters were injected with estrogen followed 44 h later by progesterone. They were then tested for sexual receptivity. After this test, their brains were removed and histologically prepared. Lesion location was determined and lesion size was quantified with a digitizing pad. Lesions which were centered in and destroyed much of the ventral tegmental area produced the greatest lordosis impairments. Mesencephalic lesions which did not bilaterally damage the ventral tegmental area had little effect. These results support the hypothesis that the ventral mesencephalon, particularly the ventral tegmental area, is an important site for the facilitative action of progesterone on sexual receptivity in estrogen-primed female hamsters. PMID- 1933410 TI - Early postnatal diazepam exposure alters sex differences in the rat brain. AB - The volume and neuron number of the sexually dimorphic accessory olfactory bulb and locus coeruleus are altered by early postnatal exposure (from the day of birth to postnatal day 16) to diazepam. After diazepam treatment, both volume and neuron number were decreased in the male accessory olfactory bulb and in the female locus coeruleus. These results indicate that early postnatal diazepam administration can bear gender-dependent teratogenic effects upon sexually dimorphic nuclei and suggest that endogenous benzodiazepines may be involved in the sexual differentiation of the brain. PMID- 1933411 TI - Role of neostriatum and nucleus accumbens in stepping induced by apomorphine and dexamphetamine. AB - Systemic administration of apomorphine and dexamphetamine are known to produce circling in rats by changing the functioning of hindlimb stepping and forelimb stepping, respectively. In the present study intracranial injections of the dopamine antagonist sulpiride were used to study the involvement of the neostriatum and nucleus accumbens in these effects. It was found that injections of sulpiride into the neostriatum, but not the nucleus accumbens, dose dependently (1-20 ng) reduced the number of apomorphine-induced hindlimb doublets without affecting the dexamphetamine-induced forelimb crossing steps. On the other hand, it was found that injections into the nucleus accumbens, but not the neostriatum, reduced the number of dexamphetamine-induced forelimb crossing steps without affecting the apomorphine-induced hindlimb doublets. This effect was not dose-dependent. The data suggest that the neostriatum, but not the nucleus accumbens, is primarily involved in the apomorphine-induced changes in hindlimb stepping, and that the nucleus accumbens, but not the neostriatum, is primarily involved in the dexamphetamine-induced changes in forelimb stepping. PMID- 1933412 TI - Response of neurons of the rat anterior hypothalamic-preoptic area to carbachol. AB - Behavioural effects of carbachol given into the hypothalamic/preoptic area have been demonstrated but there is a paucity of information about the response of single neurons to carbachol. The aim of the present study was to determine the response of spontaneously firing neurons in the rat hypothalamic/preoptic area to application of carbachol by iontophoresis or by pressure injection in a dose and volume comparable with that used in behavioural studies. Extracellular single unit recordings showed a significant decrease in mean firing rate in 82% of neurons responding to iontophoretic carbachol and in 75.5% of neurons responding to carbachol injected about 600 microns away. An increase in firing rate occurred in only 15 and 17.6% of neurons, respectively. Application of saline did not alter the mean firing rate while application of glutamate into the same areas or ejection into the vicinity of the same neurons caused an increase in mean firing rate in 94% of responding neurons. The results indicate that a decrease in mean firing rate is the predominant neuronal response to carbachol in the anteromedial hypothalamic/preoptic area of the rat and we suggest that this decrease may be associated with behavioural responses to carbachol. PMID- 1933413 TI - Maturational changes in expression of enkephalin peptides in adrenal and extra adrenal tissue of fetal and adult rabbits. AB - Met-enkephalin immunoreactivity (MET-ENKi), total enkephalin immunoreactivity (TOTAL MET-ENKi) and catecholamines were measured in adrenal and extra-adrenal tissue of fetal, newborn and adult rabbits. Met-enkephalin peptides were detected in adrenal and extra-adrenal tissue by 29 days of gestation. There were progressive increases in TOTAL MET-ENKi in both the adrenal and extra-adrenal tissue during development. In 29-day-old fetuses, MET-ENKi represented 43 and 50% of the peptide content in adrenal and extra-adrenal tissues respectively. By 3 days after birth, MET-ENKi represented only 15 and 7% of the peptide content in the same tissues. In the adult adrenals, 10% of enkephalin peptides were found as MET-ENKi. There were progressive increases in adrenal and extra-adrenal catecholamine content in the fetal and newborn rabbits throughout development. The changes in the ratio of MET-ENKi to TOTAL MET-ENKi peptides suggest differences in posttranslational processing of proenkephalin peptide during maturation. We speculate that enkephalin peptides derived from proenkephalin A are important during fetal and early newborn life and that extra-adrenal tissue may be an important source of these peptides during development. PMID- 1933414 TI - Vasoactive intestinal polypeptide (VIP) immunoreactive elements in the caudal ventral striatum of the rat: a light and electron microscopic study. AB - Under the posterior limb of the anterior commissure, a brain region intercalated between the ventral striatum and the ventral pallidum was previously identified as the interstitial nucleus of the posterior limb of the anterior commissure by de Olmos. This region, referred here as the caudal ventral stratum (VSc), is characterized by a dense plexus of vasoactive intestinal peptide immunoreactive (VIP+) axons. Double-fluorescence immunocytochemical reactions reveal that the dense VIP+ plexus is found in a region also rich in dopaminergic (i.e., tyrosine hydroxylase immunoreactive) fibers but poor in enkephalinergic terminals. The dense plexuses of VIP+ axons in VSc appear to be contiguous with those in the bed nucleus of stria terminalis (BNST) and the central nucleus of amygdala (CNA). These results support the notion that this VSc region is a part of the "extended amygdala" as proposed recently by Alheid and Heimer, and confirms that its anatomical properties are closer related to the ventral striatum than the ventral pallidum. Electron microscopic analysis reveals that the VIP+ boutons form asymmetrical synapses with dendrites and spines, and symmetrical synapses with somata of unlabeled VSc neurons. The few VIP+ neurons within this area form synapses with many unlabeled axon terminals on both their somata and dendrites. Some VIP+ neurons, however, also form axosomatic and axodendritic synapses with VIP+ boutons. PMID- 1933416 TI - Free D-aspartate and D-alanine in normal and Alzheimer brain. AB - In this report we present evidence for the presence of free D-aspartic acid (D Asp) and D-alanine (D-Ala) in the white and gray matter of normal human brains and brains of individuals with Alzheimer's disease. D-Asp occurs at about the same concentration in the gray matter of both normal (18.6 nmol/g) and Alzheimer (14.8 nmol/g) brains, whereas in white matter its concentration is more than two times higher in normal than Alzheimer brains (22.4 and 10.5 nmol/g, respectively). D-Ala occurs in white matter at approximately the same concentration in both normal and Alzheimer brains (12.3 and 13.8 nmol/g, respectively), whereas in Alzheimer gray matter the D-Ala concentration is more than twice that found in normal gray matter (20.8 and 9.5 nmol/g, respectively). However, when the results are expressed as a percentage of D-amino acid/D+L, only small differences occur in all tissues examined. PMID- 1933415 TI - Septal choline acetyltransferase immunoreactive neurons: dose-dependent effects of AF64A. AB - Two experiments were performed. In the first, the cholinotoxin, AF64A (0.5, 1.0 or 1.5 nmol/ventricle), or vehicle (3.0 microliters) was injected (ICV) bilaterally into male rats (n = 23). Choline acetyltransferase (ChAT) immunoreactive (IR) perikarya in the four subgroups of the septal complex were visualized by immunocytochemistry (PAP method) 28 days postinjection, and counted using a microprojector (x40). The 0.5 nmol/ventricle dose of AF64A significantly reduced (31%) the number of ChAT-IR cell bodies in the intermediate subgroup (rostral extension of the nucleus basalis/substantia innominata). Higher doses did not produce additional reductions. The highest dose (1.5 nmol/ventricle) of AF64A resulted in significant decreases in ChAT-IR cell bodies in the dorsal (51%) and midline (35%) subgroups (medial septum), but did not affect the number of ventral subgroup (diagonal band of Broca) ChAT-IR neurons. In the second experiment, electrolytic lesions were placed in the corpus callosum, cingulum and overlying cingulate gyrus, in order to simulate the nonselective damage seen following the 1.5 nmol/ventricle dose of AF64A. In comparison to the surgical controls (n = 3), the electrolytic lesions (n = 6) failed to significantly affect the number of ChAT-IR perikarya in any of the septal subdivisions. Thus the distinct subgroups of septal ChAT-IR neurons are differentially sensitive to the toxic effects of ICV administered AF64A: intermediate much greater than dorsal greater than midline much greater than ventral subgroup. PMID- 1933417 TI - Quantitative autoradiographic distribution of [3H]-MPTP binding in the brains of superoxide dismutase transgenic mice. AB - Recently, we have shown that transgenic mice which exhibit increased superoxide dismutase (SOD) activity are resistant to N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced neurotoxicity. Increased SOD activity has been related to impairment of cell membrane characteristics and enhanced lipid peroxidation. Thus it was thought that resistance to MPTP might possibly be attributable to alteration in the distribution of MPTP which is a highly lipophilic compound. This idea was stimulated by a previous suggestion that the resistance manifested by rats to MPTP might be due to a low level of [3H]-MPTP binding sites in brain regions which are critical to MPTP-induced toxicity. The comparison of the binding of [3H]-MPTP in the brain of SOD-transgenic mice and their nontransgenic littermates did not reveal any significant difference in either brain distribution or in concentrations of [3H]-MPTP binding between the two groups. Our data indicate that the observed lack of MPTP-induced toxicity of SOD-transgenic mice is not related to abnormal binding of the toxin in the brain of these transgenic animals which exhibit 2.07 to 3.48 higher SOD activity than their nontransgenic littermates. In addition, this study provides a normative description of the regional distribution of [3H]-MPTP binding in the brain of normal mice. PMID- 1933418 TI - Partial hippocampal pyramidal cell loss alters behavior in rats: implications for an animal model of schizophrenia. AB - A putative biological substrate of schizophrenia involves cellular pathology within the hippocampus. While hippocampal dysfunction is associated with impaired learning and memory, schizophrenics have been observed to acquire simple conditioned reflexes at rates superior to controls. The present study evaluates the acquisition of shuttlebox avoidance responses in animals with partial damage to hippocampus. Intraventricular microinjections of kainic acid (0.5 or 1.5 nM) were utilized to partially destroy the pyramidal cell population. Animals in the high dosage group acquired the response at rates superior to controls; the low dosage group performed at an intermediate level. Consequently, partial loss of pyramidal neurons may be sufficient to significantly alter simple acquisition. Results are discussed in reference to the "embryological hypothesis" of schizophrenia and mechanisms for induction of schizophrenic behavior in intractable seizure disorders are considered. PMID- 1933419 TI - Computer-aided extraction of the features of the EMG of single motor units. AB - A software-based system is presented for feature extraction of compound, action potential (EMG) recordings from single motor units. It simplifies and automates the measurement and analysis of several parameters of the action potential: peak to-peak amplitude, total duration, peak-to-peak duration, and total area. The software is based on a simple algorithm that first finds the baseline (isoelectric line; including a noise level) of each single EMG potential (waveform) and then searches for the minimum and maximum values in the array of data points representing it. The algorithm searches in both directions starting from the minimum and maximum data points (the waveform peaks) to find the beginning and ending points of the waveform. Using the indices (i.e., array-point numbers) of the four data points provided by the algorithm, the desired features are extracted and/or calculated and saved in a standard-format spreadsheet. The algorithm has a potentially widespread usefulness in a broad array of electrophysiological studies. PMID- 1933420 TI - Recovery of function in spinalized, neonatal rats. AB - Neonatal rats, when spinalized on the fourteenth postnatal day, showed minimal recovery of function in their hindlimbs. Bridging the cut spinal cord with E16 fetal spinal cord tissue did not improve functional recovery. Bridging, plus treatment with GM1 ganglioside, caused a significant (p less than 0.05) improvement in function, versus the bridged animals treated with saline. The E16 spinal cord transplants survived poorly, or not at all. Contact of the hindlimbs with a surface is necessary to elicit function. Regrowth of descending fibers into the caudal region of the cord is probably not involved in functional recovery. It is suggested that functional recovery is mediated by hindlimb proprioceptive afferents, which activate the lumbosacral motor central pattern generator. PMID- 1933422 TI - The hearing loss associated with exposure to toluene is not caused by a metabolite. AB - Exposure to toluene causes a marked hearing loss in rats, and this effect has been observed in some human solvent abusers. The issue of whether toluene or one of its metabolites is responsible for this effect has not been examined. To attempt to resolve this issue, we manipulated the metabolism, and thus the circulating levels, of toluene as follows. Two groups of rats were exposed to phenobarbital (PB) in their drinking water (0.1%) for seven days to induce detoxifying liver enzymes; two other groups had access to PB-free water. Then half of the rats exposed to PB or water were exposed to filtered air or a concentration of toluene expected to cause hearing loss. Levels of toluene in blood were markedly reduced by the PB and the excretion of hippuric acid was increased. All rats were tested for auditory sensitivity by brainstem auditory evoked response (BAER) audiometry using a 16-kHz tone pip. The rats exposed to toluene alone showed a marked reduction in the integrated BAER waveform, indicative of the expected hearing deficit. None of the other treated rats showed any deviation from controls (i.e., water and air). These results provide strong evidence that toluene itself is responsible for the auditory dysfunction. Toluene also caused the rats to increase their fluid consumption and urine output; these effects were not altered by PB. Identification of toluene as the proximal ototoxicant should facilitate the search for the mechanism of this effect. PMID- 1933421 TI - N6-cyclopentyladenosine impairs passive avoidance retention by selective action at A1 receptors. AB - The effects of N6-cyclopentyladenosine (CPA), a highly selective agonist for adenosine A1 receptors, on retention of one-trial inhibitory avoidance behavior were examined in mice. Water-deprived animals were trained to avoid drinking by pairing foot-shock with licks from a water spout. Retention was measured as the suppression of drinking (latency to drink) 48 h following training. Administration of CPA (0.15-2.25 mumol/kg) 30 min prior to training produced a dose-dependent impairment in memory of the original avoidance task. The CPA elicited deficits in retention performance were blocked by pretreatment with 8 cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A1 receptor antagonist; DPCPX (15 mumol/kg) administration alone had no effect on retention performance. These findings suggest that selective activation of a presumably central population of A1 receptors may impair retention performance and influence information processing. PMID- 1933423 TI - Comparison of quisqualic and ibotenic acid nucleus basalis magnocellularis lesions on water-maze and passive avoidance performance. AB - The present study compares water-maze (WM) (reference and working memory) and passive avoidance (PA) (acquisition and retention) deficits induced by ibotenic (ibo) and quisqualic (quis) acid nucleus basalis magnocellularis (NBM) lesions. Ibo lesions produced a large subcortical cell loss and a decrease in frontal cortex (FR) choline acetyltransferase (ChAT) activity. Ibo lesions impaired WM acquisition and PA acquisition and retention performance. Quis NBM lesions were restricted to the ventromedial pallidum, but ChAT activity was decreased in FR. Quis NBM lesions impaired PA acquisition and retention, but had no effect on the reference or working memory WM performance. PMID- 1933424 TI - Nicotinic and muscarinic interactions and choice accuracy in the radial-arm maze. AB - Muscarinic acetylcholine (ACh) systems have long been known to be necessary for accurate performance in cognitive tests. Nicotinic ACh systems have been shown to be involved as well. However, there is only a limited amount of information concerning the interactions of these two branches of the ACh transmitter system. The current study was conducted to investigate the improvement in choice accuracy caused by muscarinic and nicotinic agonists and how it is affected by antagonists of these systems. Adult female Sprague-Dawley strain rats (N = 11) were trained on a working memory task in an 8-arm radial maze. Acute injections of the muscarinic and nicotinic agonists, pilocarpine (PILO, 1.0 mg/kg) and nicotine (NIC, 0.2 mg/kg), were made alone or in combination with the muscarinic and nicotinic antagonists, scopolamine (SCOP, 0.1 mg/kg) and mecamylamine (MEC, 10 mg/kg). NIC administration caused a significant improvement in choice accuracy compared with saline (p less than 0.01) and PILO caused a marginally significant improvement in choice accuracy (p less than 0.06). The combination of these nicotinic and muscarinic agonists did not cause an additive improvement. However, the improvement caused by either agonist was reversed by both nicotinic or muscarinic antagonists. This reversal was more complete for NIC than PILO despite the fact that NIC caused a greater improvement than PILO. These results suggest that muscarinic and nicotinic components of the ACh system, which are both important for cognitive function, interact in important ways. These interactions may be critical to consider when devising treatments for cognitive dysfunction associated with cholinergic hypofunction such as with Alzheimer's disease. PMID- 1933425 TI - Cyclo (His-Pro), d-amphetamine and striatal dopamine: a microdialysis study. AB - Extracellular levels of dopamine (DA) and its metabolites (DOPAC and HVA) were monitored in the striatum of rats using in vivo microdialysis, in an attempt to elucidate the mechanism of cyclo (His-Pro) (histidyl-proline-diketopiperazine, CHP) on dopaminergic activity. Pretreatment with CHP (0.5 mg/kg SC) (n = 5) or the equivalent volume of saline (n = 5) was followed 30 min later by 5 mg/kg IP of d-amphetamine. Dialysate samples were collected and analyzed by high performance liquid chromatography with electrochemical detection (HPLC-EC). Following the initial increase in DA caused by d-amphetamine, DA levels of CHP treated rats were significantly lower than saline-treated rats across time (p less than 0.05). No difference was observed for DOPAC or HVA. It is therefore unlikely that CHP interferes with the d-amphetamine-induced inhibition of DA reuptake. Other neurotransmitter systems may be involved in the CHP-induced augmentation of amphetamine's behavioral effects. Our data, as well as previous findings, suggest that attenuation of the dopaminergic response to d-amphetamine might be best explained on the basis of striatal DA depletion, possibly via tyrosine hydroxylase (TH) inhibition. This study also indicates that a dissociation may exist between the behavioral and the striatal DA response to acute amphetamine. The data support the hypothesis that amphetamine releases DA from a newly synthesized, extravesicular cytoplasmic pool, and that intracellular striatal DA is present in considerable excess relative to the extracellular DA. PMID- 1933426 TI - Ro 5-4864, like picrotoxin, enhances EPSP-spike coupling in the freely behaving rat. AB - To help determine its mechanism of action, the convulsant benzodiazepine Ro 5 4864 was administered (15-20 mg/kg) intraperitoneally (IP) and electrophysiological and behavioral effects were compared; parallel studies were conducted with picrotoxin (PTX; 1 mg/kg). Both PTX and Ro 5-4864 produced myoclonic seizures, primarily between 15-40 min after administration; myoclonus was followed by more severe seizures after PTX. Both Ro 5-4864 and PTX produced a maximal increase in amplitude and decrease in threshold of the population spike (PS) evoked in the dentate gyrus (DG) by stimulation of the dorsal perforant path prior to peak seizure activity; start latency of the PS and initial slope and amplitude of the population slow wave (SW) were not changed. Amplitude of the PS was already increased by 5 min after administration of Ro 5-4864 and was maximally increased 1.8- to 3-fold, depending on stimulus intensity, usually by 10 min. Similarly, by 20 min after administration, PTX had also increased PS amplitude in the absence of an effect on PS latency or the SW. The increase in PS amplitude without concomitant changes in the SW suggests that Ro 5-4864 enhanced coupling between the excitatory postsynaptic potential (EPSP) and firing of the postsynaptic neurons, i.e., it enhanced E-S coupling, as has also been suggested for PTX. The similarity in the effects of Ro 5-4864 and PTX suggests that antiGABAergic effects, perhaps along feedforward inhibitory pathways, are involved in both the seizures and enhanced E-S coupling. PMID- 1933427 TI - A possible thalamic component of the auditory evoked potential in the rat. AB - An attempt is described to identify a thalamic component of the auditory evoked potential in the rat. Auditory potentials were recorded simultaneously from skull locations over the thalamus and the primary auditory cortex. From over the thalamus a slow positive response was recorded with a mean peak latency of 7.3 ms. This preceded the primary cortical response by 1.2 ms. It is concluded that this potential is a more likely candidate for a thalamic response than either a late high frequency component of the brainstem auditory evoked potential or else one of the early components of the middle latency auditory evoked potential. PMID- 1933428 TI - Joint modulation of neocortical electrical activity by nicotinic and muscarinic receptors. AB - A combination of subthreshold doses of nicotinic and muscarinic antagonist induced an increase in all the spectral components. The spectral amplitude change induced by a large scopolamine dose could not be augmented by either mecamylamine or an additional injection of scopolamine. NB lesions increased frontal slow wave activity (delta and theta amplitudes). Single or combined injections of scopolamine and mecamylamine produced a significantly smaller change in the frontal EEG amplitude values of NB-lesioned rats than in controls. PMID- 1933429 TI - Triggering module for waveform digitization. AB - A full circuit description is provided for a triggering module used to assist a small laboratory computer in digitizing muscle force- and EMG waveforms. During the stimulation of individual motor units using a standard fatigue test, a train of 13 pulses are delivered at a rate of 40 pps either intracellularly to a motor neuron, or extracellularly to functionally isolated single motor axons from among divided ventral-root nerve filaments. Trains are delivered at a rate of 1/s for the duration of the test, which may range from 120 to 3600 s. Both the force and EMG profiles undergo changes during such tests and the quantification of parameters associated with their waveforms are of interest to neurobiologists. The triggering module allows a typical small laboratory computer to capture user selected waveforms and thereby reduces the programming problems, timing constraints, storage requirements and analysis time associated with obtaining these parameters. The versatile circuit may be easily adapted to solve similar data-acquisition problems. The method was implemented on an Apple Macintosh II computer but can also be applied to other systems equipped with appropriate software and a data-acquisition card. PMID- 1933430 TI - Enkephalin-containing nerve cell bodies in the substantia nigra of the rat: demonstration by immunohistochemistry and in situ hybridization. AB - The use of a new and very sensitive immunohistochemical method, combined with intracerebral injections of colchicine, has allowed us to show that a number of nerve cell bodies immunoreactive for Met-enkephalin are present in several mesencephalic nuclei of the rat, including the different subdivisions of the substantia nigra (SN). The existence of numerous neuronal somata of this kind in the medial part of the SN pars compacta and in the lateral half of the pars reticulata is rather new. The latter has been ascertained by demonstrating a perikaryal immunoreactivity for synenkephalin in the same regions of the SN. In addition, by in situ hybridization, we have shown that neuronal cell bodies expressing the preproenkephalin A (PPA) gene are also present in the same regions of the SN. However, the fact that a strong radioautographic reaction was found only in rats which received an intranigral injection of 6-hydroxydopamine indicates that these neurons are probably not dopaminergic and that an induction of the PPA gene occurs in these animals. PMID- 1933431 TI - Effects of periodontal stimulation on VHM neurones in anesthetized rats. AB - In anesthetized rats, mechanical stimulations, the direction and intensity of which could be modified, were applied to the superior incisive while single neurone activities were recorded within the VHM region by means of extracellular glass microelectrodes. The great sensitivity of periodontal receptors to the direction and the intensity of the stimulations was demonstrated at this level. This finding, which is reported here in detail for the first time, suggests that the periodontal afferents might be involved in physiological mechanisms including food intake regulation and osteomorphogenesis. PMID- 1933432 TI - Differential actions of central alloxan upon opioid and nonopioid antinociception in rats: a further examination. AB - Previous work demonstrated that central pretreatment with alloxan significantly reduced antinociception induced by morphine and 2-deoxy-D-glucose (2DG), an opioid-mediated stressor, but not induced by continuous cold-water swims (CCWS), a nonopioid-mediated stressor. The alloxan-induced deficits in 2DG antinociception were ameliorated by coadministration of D-glucose (3 M, 3M-DG). The present study evaluated this relationship further by: a) examining whether central alloxan reduced morphine antinociception following either simultaneous 3M DG and alloxan coadministration, alloxan followed 10 days later by 3M-DG and 3M DG alone, and b) determining whether central alloxan pretreatment altered nonopioid antinociception induced by the muscarinic cholinergic agonist, pilocarpine. Morphine (2.5-5 mg/kg, SC) antinociception on the tail-flick and jump tests was significantly reduced by central alloxan. In contrast, simultaneous coadministration of 3M-DG and alloxan failed to alter morphine antinociception. This ameliorative effect of 3M-DG was not due to its ability to affect morphine antinociception, and was time-dependent in that delays in 3M-DG administration failed to affect the alloxan-induced deficit. Central alloxan pretreatment failed to alter pilocarpine antinociception on the tail-flick test, and increased pilocarpine antinociception on the jump test. That central alloxan reduced opioid (e.g., morphine and 2DG), but not nonopioid (e.g., CCWS, pilocarpine) forms of antinociception suggests a specific mode of action, possibly through disruptions of glucoprivic control mechanisms which is in keeping with the suggestion that opioid systems are sensitive to changes in central glucose function. PMID- 1933433 TI - Effects of MK-801 on rat primary afferent neurons and fibers. AB - Recent evidence suggests that glutamate and its N-methyl-D-aspartate (NMDA) receptor may participate in regulating neurite morphology and peptide expression. A previous study from this laboratory showed that treatment with the NMDA receptor antagonist, MK-801, induced an apparent increase in the density of calcitonin gene-related peptide (CGRP)-immunoreactive primary afferent fibers in the dorsal spinal cord of the rat. The present study was undertaken to extend this work by: 1) quantifying the MK-801-induced increase in CGRP immunostaining in the dorsal grey commissure/medial dorsal horn region and 2) examining the effect of MK-801 on the number of CGRP-immunoreactive primary afferent cell bodies in lumbar dorsal root ganglia. Following 7 days of MK-801 treatment, a significant increase (p less than 0.001) in CGRP immunostaining was observed in the dorsal grey commissure/medial dorsal horn. However, after MK-801 treatment, no significant difference was noted in the numbers of CGRP-immunoreactive primary afferent cell bodies in dorsal root ganglia. These data suggest that MK-801 produces significant alterations in the intraspinal projection of CGRP immunoreactive fibers without inducing immunocytochemically detectable CGRP within a new population of primary afferent neurons. PMID- 1933434 TI - Spinal cholinergic modulation of cardiovascular tone and a somatosympathetic reflex response. AB - The purpose of this study was to examine the relationship between spinal cholinergic pressor neurons and a somatosympathetic reflex response in rats. Intrathecal (IT) injection of the cholinesterase inhibitor, neostigmine (NEO), produced marked pressor and tachycardic responses without any changes in respiratory parameters. On the other hand, stimulation of the sciatic nerve produced increases in both cardiovascular and respiratory (tidal volume, minute volume, respiratory rate) responses. These cardiorespiratory responses to nerve stimulation were inhibited by IT NEO. A pressor response could also be induced by topical application of NEO to the surface of lower spinal cord, which was not altered by prior dorsal rhizotomy. These results indicate that two independent cholinergic systems exist in the spinal cord, one of which participates in the inhibitory modulation of the somatosympathetic reflex, and the other which mediates a sympathoexcitatory response. It is unlikely that the pressor response to spinal administration of NEO is mediated through this somatosympathetic response. PMID- 1933435 TI - Local infusion of calcium-free solutions in vivo activates locus coeruleus neurons. AB - Microinfusion of calcium (Ca++)-free artificial cerebrospinal fluid onto locus coeruleus (LC) neurons in vivo potently increased their discharge rate, while response of these cells to a sensory stimulus was significantly reduced. These effects resulted in part from interference with the calcium-dependent potassium conductance in these neurons, as microinfusions of solutions having barium substituted for calcium partially mimicked the effects of Ca(++)-free infusions. In addition, microinfusion of control medium containing the Ca++ channel blocker, cadmium (2-20 mM), also mimicked the effect of the Ca(++)-free solution. This study presents an effective means by which extracellular concentrations of neuromodulatory ions can be manipulated in vivo. In addition, these results indicate that extracellular Ca++ potently modulates the spontaneous as well as evoked activity of central noradrenergic neurons in vivo. PMID- 1933436 TI - Induction of temporally dissociated morphological and physiological differentiation of N1E-115 cells. AB - Clonal cells derived from neural tumors have been widely used to study the processes of neuronal differentiation in vitro. The murine neuroblastoma clone N1E-115 has recently been shown to differentiate morphologically in response to removal of serum from the culture medium. In the present study, the nature and time course of electrophysiological differentiation of N1E-115 cells maintained in serum-free medium was examined. Differentiated cells had a higher resting potential and lower input conductance than nondifferentiated cells. Differentiated but not nondifferentiated cells generated current evoked action potentials, and differentiated cells fired spontaneous, repetitive action potentials after 13 days in serum-free medium. The rate of potential change during the depolarizing and repolarizing phases of the action potential became faster as the duration of maintenance of cells in serum-free medium increased. Remarkably, morphological differentiation appeared to be complete after exposure to serum-free medium for 5 days but electrophysiological differentiation was not complete until 13 days in this medium. PMID- 1933437 TI - Role of cholinergic fibers in a center essential to animal hypnosis. AB - We previously found that the center from which animal hypnosis is controlled in the rabbit is located in the area that includes the brachium conjunctivum and locus coeruleus (LC-BC) of the brainstem. Microinjection was used to investigate functions of cholinergic fibers in this area in relation to animal hypnosis. The duration of animal hypnosis (DAH) induced by inversion was diminished to about 60% of the controls by microinjecting atropine into the LC-BC, whereas microinjection of carbachol prolonged the DAH to 3.5 times that of the controls. Flexor muscle contraction of the upper extremities, induced by electrical stimulation of the motor cortex (CFM), was enhanced by atropine and suppressed by carbachol. In normal rabbits; hard pressing on the ear base or the lumbar paravertebral area reduced CFM (pressing effect), and this effect was partially antagonized by atropine microinjected into the LC-BC. The results suggest that cholinergic fibers in the LC-BC modulate functions involved in animal hypnosis. PMID- 1933438 TI - The ascending gustatory pathway: a Golgi analysis of the medial and lateral parabrachial complex in the adult hamster. AB - This study examined the somal areas, dendritic features and orientations of neurons within taste responsive regions of the parabrachial complex, including the "waist" area that spans the brachium conjunctivum. The data were compared with those of a Golgi study of the gustatory zone of the nucleus of the solitary tract. Both fusiform and multipolar neurons were identified. Fusiform neurons had elongated somata that average 205 microns2 (range: 128-281 microns2) and generally possessed bipolar primary dendrites. Multipolar neurons had a stellate appearance and somal areas that averaged 230 microns2 (range: 109-443 microns2). These multipolar neurons possessed significantly more primary dendrites than fusiform neurons (4.0 versus 2.9 primary dendrites). Fusiform neurons were uncommon in the medial and lateral regions of the parabrachial complex but predominated in the solitary nucleus. Parabrachial neurons were usually larger and possessed more complex higher-order dendritic arborizations than solitary neurons. Computer-generated three-dimensional rotational analyses failed to demonstrate the strong orientation specificity in parabrachial neurons that characterizes gustatory solitary neurons. These Golgi studies described for the first time the morphological features of pontine neurons that could possibly receive ascending gustatory projections, and the morphological differences between neurons that receive direct peripheral input from taste receptors and the pontine targets of such neurons. PMID- 1933440 TI - Sigma (12-15 Hz) and delta (0.3-3 Hz) EEG oscillate reciprocally within NREM sleep. AB - Sleep EEG in the sigma and delta frequency bands was subjected to spectral analysis in 8 normal young adults. In each subject, power density of sigma and delta oscillated reciprocally during NREM sleep, confirming an observation made initially with period/amplitude analysis. In REM sleep, power density for both frequency bands was at its lowest levels. Correlation coefficients between power density of delta vs. 1/sigma for all artifact-free 20-s epochs of NREM sleep/night were highly significant for each subject. These results show that cyclic oscillation of EEG within sleep is not limited to delta frequencies. The reciprocal relation of sigma to delta holds implications for the EEG mechanisms of NREM sleep. This dynamic pattern may also prove useful for sleep stage scoring and for a finer empirical analysis of sleep in psychiatric and neurological disorders. PMID- 1933439 TI - Inhibition of brain MAO-A and animal behaviour induced by p-hydroxyamphetamine. AB - Intra- and extra-synaptosomal activity of monoamine oxidase-A (MAO-A) and -B (MAO B), dopamine (DA) and its main metabolites were examined to clarify the mechanism of action(s) of p-hydroxyamphetamine (p-OHA) in animal behaviour mediated by central dopaminergic systems. Intrasynaptosomal DA was oxidized by MAO-A and MAO B and this oxidation is inhibited by p-OHA. The inhibition is due to two effects: 1) uptake of DA is inhibited by p-OHA, and 2) p-OHA also inhibits intrasynaptosomal oxidation of DA by MAO-A and MAO-B. The inhibition of oxidation by MAO-A is predominant. Administration (ICV) of 80 and 160 micrograms p-OHA to mice, doses that cause various behavioural, significantly reduced striatal DA and 3,4-dihydroxyphenylacetic acid (DOPAC) levels, but greatly increased 3 methoxytyramine, without significantly changing homovanillic acid (HVA). The release of DA and blockade of DA uptake into dopaminergic neurons by p-OHA, together with preferential inhibition of the DA metabolizing enzyme, MAO-A, may contribute to p-OHA-induced behaviour mediated by the central dopaminergic systems. PMID- 1933442 TI - Morphological study of the caecal epithelium of the chicken (Gallus gallus domesticus L.). AB - 1. The structure of the chicken caecal epithelium has been investigated at macroscopic and microscopic levels (scanning and transmission electron microscopy). 2. Morphological data distinguish three regions in the caecum: proximal, with well developed villi, but smaller and less numerous than those present at mid-jejunum; medial, with longitudinal folds and small villi, and distal, with longitudinal and transverse folds and small villi similar to those of the medial region. 3. Microvilli of enterocytes from the tip of the villus of the proximal caecum are shorter and thinner than jejunal microvilli; microvilli of medial and distal regions are poorly developed. 4. There is a decrease in microvillus surface area along the villus axis as a result of the progressive decrease of microvillus length from the tip of the villus to the crypt, both in the proximal caecum and jejunum. In tip of the villus, the amplification of apical surface due to microvilli is 24, 12.7 and 14 times in proximal, medial and distal caecum, respectively, while in the jejunum the amplification factor is 33.1. 5. The higher development of proximal caecal apical surface supports the view that this region is better adapted for the absorption of nutrients that the other caecal regions. PMID- 1933441 TI - Effect of a nonpeptide angiotensin II receptor antagonist, DuP 753, on angiotensin-related water intake in rats. AB - The effect of peripheral administration of the nonpeptide angiotensin II-1 (AII) receptor blocker, DuP 753, on the dipsogenic responses to peripherally administered angiotensins I, II, and III was tested. In all cases, DuP 753 significantly inhibited the drinking response, whether administered 15 or 45 minutes prior to administration of the dipsogen. These results suggest that the drinking responses to angiotensins I, II, and III are mediated by AII-1 receptors. They also suggest that either AIII acts via the AII-1 receptor or that DuP 753 competes at an AIII-sensitive receptor. These studies also showed that when both AII and DuP 753 were given cerebroventricularly (ICV), potent inhibition of the drinking response occurred. Further, when DuP 753 was administered peripherally and AII ICV, drinking was also inhibited. Hence, DuP 753 must penetrate the brain, at least at the circumventricular sites implicated in angiotensin-related drinking. However, centrally administered DuP 753 failed to inhibit the drinking response to peripherally administered AII. This observation is presently unexplained, but may be related to the possibility that centrally administered DuP 753 is inactivated more quickly than when it is administered peripherally. Additional studies will be required to assess this. PMID- 1933443 TI - Histological and histochemical studies on the chicken lingual glands. AB - 1. Morphological and histochemical observations were done on the chicken anterior and posterior lingual glands. Histology, ultrastructure and glycoconjugate histochemistry were investigated by means of light and electron microscopy using staining specific for complex carbohydrates. 2. In the anterior lingual glands there are lateral and medial zones showing different morphological and tinctorial features. The secretory cells are typical mucous cells. 3. Histochemical reactions revealed the presence of acidic glycoconjugates with terminal sialic acid residues, and glycoconjugates vicinal diol and sulphate groupings in the secretory granules. 4. It is suggested that the main functions of lingual glands are the lubrication of boli and protection from micro-organisms. PMID- 1933444 TI - Long-term goose breeding for egg production and crammed liver weight. AB - 1. Results of an 8-year (1981 to 1988) period of breeding geese for egg production and crammed liver weight, including phenotypic and/or genetic parameters for various traits (1982 to 1985), as well as line tests (1987 to 1988), are summarised for two lines. 2. The regressed annual genetic gains over years were 2.7 eggs and 30.8 g crammed liver. However, there was a decline in the rate of genetic progress after 4 years of selection. 3. Heritability estimates were found to be relatively high for most traits, whereas phenotypic and genetic correlation coefficients between traits were rather low, as would be expected from lines not previously subjected to an intense selection programme. 4. Phenotypic correlation coefficients between part-period records and full-period egg production, suggest that 3-month (October to December) records may be adequate to identify most of the best first-year layers. However, sexual maturity should be treated as a separate trait. 5. The cross between the 'Grey' (male) line, superior in crammed liver weight, and the 'White' (female) line, excelling in egg production, seems to be superior to the pure lines, in a fully-integrated enterprise. PMID- 1933445 TI - Chromosome analysis of early embryonic mortality in layer and broiler chickens. AB - 1. Twenty-three lines of chickens, obtained from grandparent stocks of 4 Australian breeding companies, were analysed to determine the incidence of early embryonic mortality attributable to chromosome abnormalities. The lines included 10 layer strains, consisting of 6 White Leghorn, 2 New Hampshire and 2 Australorp lines, and 13 broiler lines. 2. A total of 10,730 eggs was examined after 3 d incubation; of these 9746 (90.8%) were fertile. Abortive embryonic development was observed in 1379 (14.1%) of the fertile eggs. This consisted of 952 (69.0%) dead and dying embryos, including 646 malformed and 427 (31.0%) membranes without embryos. 3. Early embryonic mortality was found to vary from 9.8 to 26.8% (average 16.4%) in broiler lines and from 8.0 to 27.9% (average 11.9%) in layer lines. 4. Among 898 abortive embryos analysed, 112 had abnormal chromosomes consisting of 27 haploids, 38 haploid-euploids, 24 triploids, 16 diploid polyploids, 4 aneuploids, 2 tetraploids and 1 translocation. 5. In broilers and layers respectively, chromosome abnormalities were responsible for 4.4 to 28.1% (average 11.8%) and 7.4 to 25.0% (average 13.4%) of the early embryonic mortality. 6. The overall frequency of chromosome abnormalities in all fertile eggs varied from 0.7 to 3.7% for the broiler lines and 0.7 to 3.4% for the layer lines. PMID- 1933447 TI - Metabolic differences between White Leghorns selected for high and low residual food consumption. AB - 1. From each of two populations of White Leghorn laying hens, 6 'efficient' and 6 'inefficient' hens were used in energy metabolism studies involving indirect calorimetry with activity measurement. 2. Hens classified as efficient or inefficient with respect to residual food consumption had comparable body weight and production. 3. Efficient and inefficient hens showed similar energy metabolisability, cloacal temperature, shank dimension and egg composition. 4. However, efficient hens produced less heat; activity-related heat production accounted for 29 to 54% of the difference in total heat production between efficient and inefficient hens. 5. Plumage quality also explained some of the difference in heat production, but to a lesser extent (14 to 19%). 6. Adjustment for heat increment of production changed the heat production difference slightly (-5 to 1%). 7. What was finally left unexplained (100 - 54 - 14 + 5 = 37% to 100 29 - 19 - 1 = 51%) was of the same magnitude as activity-related HP and is discussed in relation to basal metabolic rate. PMID- 1933446 TI - Effect of method and phase of nutrient restriction during rearing on productive performance of light hybrid pullets and hens. AB - 1. An experiment was conducted to study the effect of method (low-lysine or quantity of food) and phase (starter or grower) of restriction during rearing on growth and laying performance in Leghorn hybrids. 2. A reduction in body weight gain was achieved by feeding pullets a low-lysine diet in either the starter phase (0-6 weeks of age: 4.0 g/kg digestible lysine) or the grower phase (7-18 weeks of age: 3.0 g/kg digestible lysine). 3. In each phase, the lysine restriction was compared with a daily food restriction, in which pullets received a quantity of food sufficient to pair-gain with their lysine-restricted counterparts. 4. The delay in onset of production was greatest in the lysine restricted birds, for both phases of restriction. 5. Hens restricted during the grower phase laid heavier eggs than those restricted during the starter phase, despite having similar body weights at end of rearing. This effect was not influenced by the restriction method. 6. Production traits varied between pullets reared on different feeding strategies up to similar body weights at 18 weeks and onwards. It is concluded that body weight is not the only factor determining laying performance. PMID- 1933448 TI - The possible prediction of fatness in broiler chickens by biochemical measurements on adipose tissue. AB - 1. The possible prediction of fatness in 6-week-old broiler chickens was examined by measuring lipoprotein lipase (LPL) activity and lipid content in the abdominal adipose tissue. 2. Fat pad weight, as representing the degree of fatness in broiler chickens, was moderately well correlated (r = 0.54) with lipid content (g/100 g pad) and negatively correlated with LPL activity (r = 0.13). 3. It was concluded that the measurement of lipid content in samples from adipose tissue can be indicative of fatness of birds, while enzymic measurements are less valuable. PMID- 1933449 TI - Further investigations on protein requirement of genetically lean and fat chickens. AB - 1. Genetically lean (LL) or fat (FL) chickens were fed from 28 to 42 d of age on one of 6 diets with different protein contents (from 73 to 208 g/kg). In order to keep a constant amino acid balance the experimental diets were made by diluting a well-balanced protein-rich diet with a protein-free diet. 2. Dietary protein influenced the growth rate of both genotypes similarly. However, maximum weight gain was reached in LL at a lower protein intake than in FL. 3. Regression between total protein gain (body protein + feather protein) or body protein gain and protein intake exhibited significantly different slopes, that of LL being superior to that of FL. 4. At a given protein intake, feather protein gain was also superior in LL to FL. Moreover feather protein, as a percentage of total protein gain, was superior in LL to FL. When the dietary protein fell below 126 g/kg, feather protein represented a higher proportion of total protein gain. 5. Multiple linear regressions of protein intake (as the dependent variable), and body weight and protein gain or weight gain (as the independent variables) suggest that the maintenance requirement for protein is similar in both lines but that the protein efficiency for growth is significantly superior in LL. 6. In a second experiment both genotypes were offered either a single high protein diet (232 g/kg) or a single medium protein diet (186 g/kg) or had free-choice between a high (269 g/kg) and a low protein (145 g/kg) diet. In free-choice feeding, FL chickens selected an overall dietary protein content which was significantly lower (179 v. 200 g/kg) to that of LL. In both genotypes, free-choice feeding led to fatter and less efficient chickens than predicted by the linear regression between adiposity or food conversion and protein content. PMID- 1933450 TI - Plasma concentrations of luteinising hormone and body weights during somatic maturation in intact and castrated Australorp cockerels from a line of hens selected for increased ovulation rate. AB - 1. Plasma concentrations of luteinising hormone (LH), comb size and body weight were measured between 46 and 208 d of age in intact and castrated cockerels from lines of selected and control Australorp domestic chickens. The selected line had been selected for increased rate of lay by reducing oviposition intervals within sequences. The cockerels were reared and maintained on 15.25 h light/d. 2. Concentrations of plasma LH in the intact control cockerels were low in the 'immature' phase (less than 100 d old) and increased during the 'mature' phase (older than 175 d) with a peak occurring when the testes are beginning to grow at the onset of the 'mature' phase. In comparison with the control line of cockerels, the selected line had significantly higher plasma LH concentrations at the onset of the 'mature' phase. Selection had no effect on the mean concentration of plasma LH in either the immature phase or a few weeks after the onset of the mature phase. 3. There was no effect of selection in sibling females for higher rates of lay on changes in comb size or body weight during sexual maturation in the intact cockerels. 4. Castration at 45-46 d of age resulted in increased plasma LH concentrations and no comb growth. Plasma LH concentration increased progressively between 40-208 d. There was no difference between the two lines of cockerels in plasma LH concentration or rate of body growth after castration. 5. It is concluded that selection of females for a change in the rate of egg production has resulted in increased plasma LH concentrations in sibling males around the onset of sexual maturation. Selection appears to have caused this effect by altering an unidentified component of the inhibitory feedback mechanism which controls the tonic secretion of LH. PMID- 1933451 TI - Effect of metyrapone on the timing of oviposition and ovarian steroidogenesis in the laying hen. AB - 1. The purpose of this study was to observe the effects of metyrapone on the time of oviposition and LH-stimulated steroidogenesis by granulosa cells and small yellow follicles. 2. In experiment 1, White Leghorn hens were injected for 11 d with 240 mg metyrapone 5 h before 'lights off'. Control hens were injected with 1 ml of vehicle (PEG-400). Metyrapone treatment resulted in a 28% decrease in the rate of lay and the modal frequency of the time of oviposition was phase-shifted by 15 h. 3. In experiment 2, hens were injected with 240 mg metyrapone 5 h before 'lights off' or at 'lights on'. While metyrapone treatment reduced the rate of lay, a clear phase-shift in the distribution of oviposition was not observed. Basal and LH-stimulated progesterone synthesis by the granulosa cells of the largest follicle and oestradiol synthesis by small yellow follicles was significantly reduced. 4. Metyrapone treatment significantly reduced basal, but not LH-stimulated output of androstenedione by whole small yellow follicles compared to that observed in control hens. 5. The addition of metyrapone in vitro to isolated granulosa cells from the three largest preovulatory follicles inhibited LH-stimulated progesterone production in a dose-specific manner. 6. The results of this study suggest that the ability of metyrapone to perturb the open period is a pharmacological effect mediated through inhibition of ovarian and adrenal steroidogenesis. PMID- 1933452 TI - Diurnal variation in heat production related to some physical activities in laying hens. AB - 1. Heat production, standing and eating activities, and hourly food intake of 4 laying hens were observed simultaneously and the effects of activity and food intake on heat production were studied. 2. Average heat production during the dark period (20.00 to 06.00 h) was 18.9 kJ/kgW0.75 h which was 33% lower than that during the light period. About 76% of the light-dark difference in the rate of heat production was probably associated with activity and posture. 3. Standing time, which included a range of behavioural activities, occupied 90% of the light period and the increased rate of heat production associated with standing was estimated to be about 18% of daily heat production. 4. Eating time occupied 40% of the light period; the heat production associated with eating activity represented about 5% of daily heat production or 3% of ME intake. 5. Because the regression of heat production on time spent eating agreed with the regression of heat production on hourly food intake, it is suggested that the energy expenditure associated with ad libitum feeding can be estimated for hens from the regression of heat production on hourly food intake. PMID- 1933453 TI - Use of limited daily access to food in measuring the heat production associated with food intake in laying hens. AB - 1. Two experiments were carried out to determine the heat production associated with food intake in laying hens allowed access to food for one (experiment 2) or two hours (experiment 1) daily. 2. In experiment 1, heat production in the fed state was measured for two successive days after 46 h of food deprivation. The rate of heat production in the fasting state was measured from 47 to 69 h after feeding. 3. In experiment 2, heat production was measured at 4 fixed food intakes: 100, 70, 40 and 0 g/bird. Heat production associated with food intake, eating activity, net availability of ME and maintenance ME requirement was estimated. 4. Heat production after 46 h of food deprivation did not differ from that after 22 h of deprivation. In the hens receiving 100 g of food, heat production reached the pre-feeding level by 20 h after eating; the hens with lower food intakes reached the pre-feeding level more rapidly. It is suggested that the heat production associated with feeding had been eliminated by 22 h after eating. 5. Heat production associated with feeding was 16% of ME intake. Because the total energy cost of eating activity was only 0.8% of ME intake, the heat production associated with food intake in the limited-access hens came mainly from the effects of digestion, absorption and metabolism of the ingesta. 6. The net availability of ME was estimated to be 0.84. The estimated maintenance ME requirement was 569.6 kJ/kgW0.75 d. PMID- 1933454 TI - Hepatic 5'-deiodination in chickens from lines selected for high and low body weight and their F1 cross. AB - 1. Assay conditions for measuring hepatic 5'-deiodinase (5'D) activity at initial velocity, using reverse T3 as substrate, have been validated for adult chicken liver. 2. The characteristics of hepatic 5'D activity in adult chickens from lines selected for high (HW) and low (LW) juvenile body weight are similar to those in mammals and in the other birds that have been investigated. 3. Chickens from the HW line have significantly higher specific activity of hepatic 5'D, and thus potentially higher T3 production, than those from either the LW line or the F1 cross (HL) between the HW and LW lines. PMID- 1933455 TI - Role of magnesium in egg shell formation in the domestic hen. AB - 1. The effects of feeding diets containing various amounts of magnesium on plasma concentration of calcium and magnesium in the domestic hen were investigated. 2. Plasma concentrations of calcium and magnesium decreased during shell formation in all birds. 3. Plasma magnesium content and egg shell thickness were severely reduced in birds given diets containing either 207 or 132 mg Mg++/kg. 4. Using electron microscopy, a precise correlation was observed between the normal distributions of magnesium and organic material across the egg shell of the domestic hen. PMID- 1933456 TI - Histamine in egg yolk: heat resistance and relation to production status. AB - 1. The presence of histamine in egg yolk, its losses during storage, incubation and heating, and its relationship to cage density stress and the egg production status of hens are described. 2. A significant (P less than 0.05) reduction in the histamine concentration of egg yolk was noted after incubating or heating egg yolks or on storage eggs. 3. Histamine concentration was greater in the yolks of high egg producing hens. 4. The concentrations of histamine in egg yolks did not change significantly (P less than 0.05) on keeping the hens individually in a cage, pairing them in the same size cage or after separating them again to individual cages. PMID- 1933457 TI - Heritability estimates of components of incubation mortality in White Leghorns. AB - 1. A total of 39,280 eggs obtained from two selected White Leghorn strains over 4 generations representing 290 sires were incubated. 2. The unhatched eggs were broken open for examination of embryonic developments and classified as early dead (0-11 d), late-dead (12-22 d) and pips. 3. The sire-component heritability estimates (%) pooled over years in the two strains, respectively were 8.5 +/- 1.5 and 7.6 +/- 1.4 for total mortality; 0.5 +/- 0.5 and 6.3 +/- 1.2 for early-dead; 5.8 +/- 1.2 and 5.5 +/- 1.1 for late-dead and 5.0 +/- 1.1 and 3.1 +/- 0.9 for pips. PMID- 1933458 TI - Effect of dietary sorbitol on the performance of broilers. AB - 1. The effect of dietary sorbitol on the performance of broilers was investigated. Male and female broilers were given a control diet or a sorbitol diet (100 g/kg diet) ad libitum from 29 to 57 d of age. 2. Body weight gain, food intake, food efficiency and the ME values of the diets were not significantly different. Absolute and relative weights of abdominal fat were significantly reduced in birds given the sorbitol diet. 3. Compared to the control diet, the diet containing sorbitol lowered the serum glucose, total cholesterol and very low density lipoprotein concentrations. PMID- 1933459 TI - Pilot-scale testing of the competitive exclusion method in chickens. AB - 1. The efficacy of a commercial competitive exclusion (CE) product, BROILACT, was tested in pilot-scale trials involving groups of 100 broiler chicks. 2. Each group was challenged with Salmonella infantis through contact with infected seeder birds and numbers of salmonellae in the caecal contents were determined weekly. 3. The performance of the birds was also monitored over a 5-week period. 4. The results showed a gradual decline of the infection, even in the untreated groups, and a dose-dependent response to treatment. 5. The treatment had no significant effect on the performance of the birds. PMID- 1933460 TI - [Outpatient emergency services]. AB - Emergency is felt very differently according to the level of education, and the sensitivity of the patient and his family circle. Pain is often the alarm but a physician only is able to appreciate the seriousness and the development of a seriously threatening emergency, which slowly evolves in their beginning but becomes degraded afterwards. The only victims who are operated on the first hour, the golden hour, take chance to survive. But there are only 2 or 3 golden minutes to rescue a cardiac arrest. Quicker an effective treatment is done, better the results are. If time is lost, a tissular hypoxia settle and lead to multiple organ failure especially in the brain. Then the dead come in more or less longer time whatever it is done: it's the irreversible shock which drive to the brain death. In the beginning the only patient and his family circle are able to do something. From that you can understand the importance of public education and alert organization for getting suited and early aid. The attending physician have to educate his patients as they are able to recognize the signs of a real seriousness. Telephone play an essential role especially because the dial 15 for health free call is now put in service in France. The phone questioning allows medical regulation of "SAMU-15" (EMS-dial 15 Centre) to dismiss most of the ill founded calls and to carry the patient in an hospital able to immediately treat him efficiently. The emergencies organization is inspired by two principles: 1. without any loss of time all patient shall fully treated, possibly on the spot. 2. effective intensive care shall be done to avoid tissular hypoxia. Hence the rescue medicalization and the emergency medical system. These principles are the basis of organization of french SAMU whom control role is also to inform the receiving hospital for preparing the reception. The 6.1.1986 french law had defined the emergency medical system, legalizing the SAMU, and fixing their role in connection with policy and firemen. The equipment of ambulances is well standardized and they should radio connected with SAMU. Helicopters may give inestimable service to carry patients in well equipped center as U.S. trauma centres. Small hospitals should only treat small emergency according their means in personnel and equipment. PMID- 1933461 TI - [Emergency care at the hospital]. AB - Emergencies are very diversified: clinical setting, age, sex, circumstances, medicine, surgery, psychiatry, specialties. The admission into the specific departments depends on geographical, demographical features (distances to be covered...). They are theoretically unscheduled but sometimes out-hospital messages can be sent to improve the reception or to decide a very short circuit. Emergency rooms exist in most hospitals and are not so often appropriate. Emergency reception requires a place and a technical assistance where to get in touch with and to perform as quick as possible the formalities, first diagnosis and first aid procedures and orientation to the appropriate department. As a main frame in the network of assistance and care, emergency department ought to be a unique place with multiple disciplines (medicine, surgery, psychiatry), where universal first aid technical assistance and unified working would open to al hospital departments or a piece of hospitals. This structure relies on well dispatched areas, with easy ways, many examinations, simultaneous actions, urgent complementary tests and families reception. A hospital, practitioner must be in charge, whom speciality deals with emergency. Staff must include on-call doctors who can be helped by at-home physicians and many competent paramedics: nurses, health workers, stretcher-bearers, X-ray handlers, drivers, operators, secretaries, social workers, hostesses... Specific arrangements must be taken for special X-rays, biology and hospital reception of medico-surgical, obstetrical, psychiatric, social, medico-legal and medico-judicial emergencies. Running of that structure, mainly facing severe emergencies, must go together with out hospital medical advises, patients admission for some time or a brief relief (control and social cases). In all cases, connection between out-hospital set ups, various medical sittings and hospitals in the main goal which must be achieved with the S.A.M.U. Emergency medicine is universal, sequential, discontinuous with a social aspect open to a town or a district. If someone wants to be technically irreproachable, he needs to get together most of the existent structures to have a performant material and as much and efficient staff as possible. PMID- 1933462 TI - [Trauma emergency care]. AB - The organization of trauma care within the country is essential. Hospitals able to provide optimal care for the injured patient must be selected. Every hospital have to evaluate its capabilities and resources and its places in the emergency medical services system. The number of hospitals defined to take care of severely injured patient should be defined by many factors: geography and population density, capable personnel immediately available priority of access to sophisticated laboratory and radiologic services, operative rooms and intensive care units. University Hospitals should have a trauma service connected with the department of surgery to take care of severely injured patients. General hospitals are an important resource to take care of others trauma patients. PMID- 1933463 TI - [The modern treatment of myocardial infarction by coronary reperfusion: impact on the organization of care]. AB - The new treatment of myocardial infarction in the acute phase is effective if it is applied as early as possible after the onset of ischemia. The concept of extreme emergency implies a change in the overall management of the patients, a reorganization of medical care and major increase in expenditures. Price disparities of thrombolytic agents and variability in complementary reperfusion therapies have a impact on hospital cost of thrombolysis. While individual patients unquestionably benefit from this new methods, further studies are needed to evaluate the increase in health expenditures involved and the economic repercussions of avoidance or limitation of myocardial infarctions. PMID- 1933464 TI - [A new mode of pediatric emergency care: the emergency and rapid diagnosis center of the Enfants-Malades Hospital, Paris]. AB - Daily approach and management of routine emergencies at public hospital is often inconvenient. A new mode of welcome and management of surgical and medical pediatric emergencies undergone at the Enfants-Malades hospital, Paris. The concept of rapid diagnosis requires the permanent presence and competence of full responsible senior. Psychological consequences of urgent medical event is diminished. The rate of hospitalisation is dramatically reduced. Using computer and original adequate software increase the quality of services and supply many precise epidemiological informations previously bad known about routine pathology. 21162 patients were registered during the first year of functioning. Only 18% of medical pediatric emergencies and 12% of surgical and traumatological pediatric emergencies required hospitalisation. Those new concept and management of such pediatric emergency unit require special psychological and the technical training of nurses and determined medical staff. PMID- 1933466 TI - [Hospital emergency care: socioeconomic problems]. PMID- 1933465 TI - [Teaching emergency medicine]. AB - In France, emergencies are taught: to all medical students in the course of their studies; a specific emergency course being rarely given as such; to physicians who want to practice in emergency system: transport, emergency rooms, in association with intensive care medicine. The head of the emergency service should have a full time position, and whatever his original specialty, should receive a specific education in critical care medicine. Nurses who attend different congresses to complete their formation are not yet rewarded with a specific status. In addition, first aid measures should be thought to the general public, so it can help injured persons. PMID- 1933467 TI - [Reflections on the law relating to the protection of persons in biomedical research--concerning trials and experiments not about drugs]. AB - This law, called the law of Huriet, was initially meant to control clinical trials of new medications and to protect "normal volunteers". It has been extended to all trials and all human experimentation, including those undertaken as a last resort and those used for research. It also concerns all new interventions or techniques in which experimentation is included in the therapeutic act, and which are the origin of real progress, day after day, in all manual activities. The example of interventional neuroradiology allows us to understand the consequences/risk of this law on the progress of this technique. Because of the lack of structure defining the acquisition of scientific knowledge in this field, this law will not be able to be applied, and the penalties proposed for not applying the law will result in many law suits. PMID- 1933468 TI - [Plants as a source of research in antiviral activity. Example of the Haemanthus albiflos bulb]. AB - The antiviral potency of an hydroalcoholic extract from Haemanthus albiflos (AMARYLLIDACEAE) bulb was investigated. Experimentations were conducted on continuous cell lines (BGM, MA 104, Hep 2) seeded in microplates. Three viruses from the RNA group (Poliovirus type I, Vesicular Stomatitis Virus type 11 and Simian Rotavirus SA 11) and two from the DNA group (Adenovirus type 5, Herpes Simplex Virus type 1) were tested. Important reduction in yield of viral infectivity was observed with the RNA group (respectively 6,4 and 4,5 logarithmic units order of magnitude). PMID- 1933470 TI - [Prostitution and public health]. AB - The attitude of public services concerning prostitution was inspired by the fear of venereal diseases. In regimenting prostitution, the state recognised that they were trying to control it. This law was a total failure and was abolished in 1946. The worrying development of sexually contagious diseases (AIDS) will start again the that was dormant with the victory of antibiotherapy on venereal diseases. The proposition to return to regimentation with there opening of "maisons closes" will also restart the debate. These measures will be inefficient against illicit prostitution and are in contradiction with our convictions and morals, and of course with our international obligations. Prostitution is now part of our society and is longer illegal, but soliciting in a public place is still an offence. The prostitute is judged as being permanently in breach of the law, contrary to the opposite sex where no responsibility is acknowledged. We proposed to associate judges, doctors, police force and prostitutes to give some consideration and think of this problem so that this part of the population do not stay on the fringe of our society and that they can have the same rights, particularly the right for housing and health services, as, unfortunately the majority of prostitutes do not have "social security". PMID- 1933469 TI - [Sensory syndrome of the cheiro-oral area due to a local lesion of the thalamus: contribution to the knowledge of the nervous system in humans]. AB - A cheiro-oral syndrome with sensory disturbances of the hand or fingers and the corner of the mouth on the same side may be due to a contralateral thalamic lesion as demonstrated by carefully studied anatomoclinical cases. The lesion is situated in the inferior and internal part of the ventral posterolateral (VPL) nucleus and the most external part of the ventral posteromedial (VPM) nucleus. These data show that, on the thalamic homonculus, the representation of the hand (in the VPL nucleus) is in close contact by its radial edge with that of the corner of the mouth (in the VPM nucleus). They illustrate the interest of the anatomoclinical method for the knowledge of the CNS in man. Such contributions provide modern neurologic imaging technics with the necessary anatomical basis. PMID- 1933471 TI - [A cursed duo: HIV infection and tuberculosis]. AB - Tuberculosis remains a health problem of extraordinary magnitude, especially in developing countries. Unfortunately, many of the same countries have the additional burden of a remarkably high prevalence of HIV infection. Because of the inherent capacity of tubercle bacilli to take advantage of deficiencies in cell-mediated immunity, tuberculosis has become an extremely important infectious complication of HIV disease in those developing countries in which the two infections coexist; the same is true, although to a lesser extent, in developed countries among those groups of patients with HIV infection, in which there is also a high prevalence of remotely acquired tuberculosis. PMID- 1933472 TI - [Bronchial asthma: hypodense macrophages of the airway]. AB - Alveolar macrophages (AM), together with other cells such as eosinophils, have been implicated in the bronchial inflammation associated with asthma. Examination of bronchoalveolar lavage (BAL) fluid has shown that these cells are activated and that the degree of activation is correlated with both the clinical severity of asthma and with the level of bronchial hyperreactivity. The cell population recovered by BAL is normally heterogeneous with regard to AM and this study was designed to investigate whether the proportion of hypodense AM is greater in asthmatics (n = 12) compared to normal subjects (n = 10). Our results show that AM from asthmatic donors are mainly found in the fractions corresponding to low densities (1.03 to 1.04 g/ml) whilst those from normal donors are found at higher densities (1.07 g/ml). Examination of the cells by electron microscopy showed that the hypodense AM displayed the morphological characteristics of activated cells in contrast to the normodense AM which had the characteristics of quiescent cells. In order to determine whether this increased activation was a result of an expansion in the AM population following recruitment of monocytes from the medulla, we studied the functional characteristics of cells recovered from each of five fractions as assessed by their ability to release oxygen-derived free radicals. No differences were observed between AM recovered from the five different density fractions in either asthmatics or in normal subjects. In conclusion, if there is a difference in the density of AM from asthmatics as compared to normal subjects, it is unliked to be due to the recruitment of new cells, but rather a result of an accelerated progression from a mature but resting state to an hyperactivated state. PMID- 1933473 TI - [Heart transplantations: impact on female fertility]. AB - Improvements in the management of patients with cardiac transplantation make it possible for these patients in the child-bearing age to expect a pregnancy. In fact, since 1987, several cases of pregnancy after cardiac transplantation have been reported. We report here two cases of successful pregnancy two years after cardiac transplantation. First Case. Pregnancy was uneventful until 36 weeks of gestation with no evidence of transplant rejection. At 38 weeks of gestation, a cesarean section was performed for increasing blood pressure, cholestatic pruritus and cephalopelvic disproportion. Cesarean section was performed under regional anesthesia and a healthy baby boy of 2680 gr was delivered. The patient was discharged one week after. Eighteen months after, both the mother and the baby are in good condition. Second case. Pregnancy was complicated by severe maternal anemia and fetal hypotrophia. Because of increasing renal insufficiency and pre eclampsia, a cesarean section was performed under regional anesthesia at 36 weeks of gestation. Delivery of a healthy baby girl of 1700 g. Five other cases have been reported. Cesarean section performed in september 1984 for a patient who underwent cardiac transplantation in 1980. Delivery of a healthy baby of 3280 gr. Death of the mother five months after following heart transplant rejection. Vaginal delivery performed in august 1986 for a patient who underwent cardiac transplantation in 1984. Delivery of a preterm baby at 31 weeks of gestation who survived without any sequelae. Vaginal delivery performed in august 1987 for a patient who underwent cardiac transplantation in april 1985. Delivery of a healthy baby of 2550 gr at 38 weeks of gestation. Vaginal delivery of twins (baby girl of 1200 and 1100 gr) in april 1988 of a patient who underwent cardiac transplantation in 1986. Vaginal delivery at 38 weeks of gestation performed in november 1990 for a patient who underwent cardiac transplantation in 1986. All the cases reported showed that: The foetus is not affected by the immuno suppressive treatment of the mother. This was already known for pregnant patients with renal transplant. The cardiovascular changes associated with pregnancy are well tolerated by the heart transplant. Preexisting hypertension is increased, particularly during the third trimester of pregnancy and during labour. The incidence of preterm labor is increased in patients with heart transplant. Transplant rejection never occurred during pregnancy. PMID- 1933474 TI - [Dietary importance of vitamin A: risks for the consumer]. PMID- 1933475 TI - [Eulogy on Jean Bretey (1903-1989)]. PMID- 1933476 TI - [Salvage surgery in cancers of the larynx after curative dose radiotherapy]. AB - Surgery catch up radiotherapy failures. Oncologic results are satisfactory. Rescue surgery can be to underline, doesn't synonymous of total laryngectomy. PMID- 1933477 TI - [The scientific value and applications of magnetotherapy]. PMID- 1933478 TI - [Collagens of the internal saphenous vein, normal and varicose, as a function of age]. AB - The normal venous vein contains more collagen in the young subject than in the ageing subject. This is confirmed by the decrease of thickness of aged venous wall indicating that the fibrosis present in the aged subject is atrophic in nature. Collagen content of the varicose vein wall remains practically unchanged with age: the varicose vein is a dysplasic vein. PMID- 1933479 TI - [The history of mitochondrial encephalomyopathies]. AB - At the end of the XIXth century, the first cases of primary progressive ophthalmoplegia reported were related to a primary degeneration of the oculomotor nuclei; and this concept was accepted until there were considered of purely muscular origin in the 1950's. From this time and during twenty years these cases were reported as ocular myopathies. However the coexistence of neurological abnormalities and above all, the presence of mitochondrial abnormalities in the muscles, the brain and the tissues rich in energy, gave ground to the concept of mitochondrial encephalomyopathies. Then the nature of the dysfunctioning was assessed through biochemical studies, mainly the enzyme deficits of the respiratory chain mitochondria. But correlations between clinical and biochemical data were still difficult as these cases corresponded either to muscular damage (myalgia, exercise intolerance), either to various neurological alterations (epilepsy, cerebellar syndrome) or to multisystemic manifestations. Molecular biology technics introduced the notion of mitochondrial inheritance which contributed to underline the identity of certain varieties, mainly the Kearns and Sayre Syndrome. The increasing number of cases with mitochondrial abnormalities leads to the inverse approach: in central or peripheral damage of the nervous system or in very variable muscular alterations, the investigation of a mitochondrial dysfunctioning is justified and shows the way to possible therapies. This evolution of concept is remarkable in the history of medicine. An abnormality which, at first, was considered as an esthetic alteration, became the subject of the study which, through the advances of the clinical data, of the pathological anatomy, biochemistry and genetics, explained the mechanism of several alterations of the muscles and of the nervous system. PMID- 1933480 TI - [Treatment of ilio-femoral venous thromboses with surgical thrombectomy]. AB - Surgical thrombectomy which has been commonly performed in the past is now abandoned by most teams. Nevertheless some surgeons have gone on performing venous thrombectomies with good results. We have performed venous thrombectomy in 91 acute ilio-femoral vein thrombosis associated with inferior vena cava or superficial vein involvement in respectively 35% and 86% of the cases. The mean estimated age of the clot was 5 days. Ilio-femoral thrombectomy was carried out under general anesthesia using a Fogarty catheter introduced through a common femoral venotomy and the removal of the distal clots by mean of massages maneuver. In case of vena cava involvement, direct caval venotomy was carried out by a right sub-costal approach. A temporary arterio-venous fistula in the groin was associated in 89% and a partial interruption of the vena cava in 55% of the cases. No operative death and no peri-operative pulmonary embolism were observed. Post-operative ilio-femoral vein patency rate was 85% without recurrence after closure of the arterio-venous fistula. A venous thrombectomy in selected cases appears to be more efficient than intra-venous heparin or thrombolytic therapy. Indications of venous thrombectomy are ilio-femoral or ilio-caval vein thrombosis of less than 7 days duration. Patients who are non ambulatory or with limited life expectancy are not likely to benefit from surgery. Venous thrombectomy is not recommended in patients with inflammatory or tumoral pelvic or retroperitoneal lesions, coagulopathies, peripheral arterial or significant heart diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933481 TI - [Nitrates in drinking water and cancer]. AB - Nitrates originating from food and particularly from water are supposedly precursors of carcinogenic N-nitroso compound (NOC) formed within the organism. According to Correa and al. these transformations could be a consequence of bacterial gastric pollution resulting from certain hypochlorhydric conditions. Much epidemiological research has tried to establish a relationship between exposure to nitrates in drinking water and cases of gastric cancer. The present article deals with research into this relationship in France, in a region where the rate of nitrates in water supplies is among the highest. Death statistics (from cancers of the digestive and urinal tracts) are issued by INSERM and these of the population by INSEE. Towns are classified according to nitrate concentration and the number of deaths is established according to tumour detection by sex and age. Research into death rate divergencies is found by chi 2 and the correlated coefficient. The average relative risk for any age group is calculated for all types of cancer. Research on frequency is carried out from tumour records. Comparative frequency rates are established by direct standardisation according to the structural age of any one European population. Results are analysed in relation to (1) mortality rates and (2) incidence rates. (1) None of the cancers studied, be they of the digestive or urinary systems, whatever the age on sex, is significantly linked to the quantity of nitrates in water supplies. When all these cancers are taken into account, the death rate does not vary significantly for increasing concentration of nitrates. Towns exceeding the maximum concentration permitted by law do not have a higher mortality rate than other towns. The overall can incidence rate in the Nord-Pas de-Calais regions of France is 11.8 per 100,000 inhabitants. The average European rate is 18.3 per 100,000 for men in the Nord region and 20.5 in the Pas-de Calais; for women, 5.9 and 7.2 respectively. These rates are comparable to those in other French regions. The incidence rate for gastric cancer is not significantly different for inhabitants of towns exposed to water containing more or less than 50 mg/l. The absence of links between cancer and nitrates water research into possible methodological expedients necessary. A certain number of factors (consumer habits, diet, population mobility) can, for the same concentration of nitrates, modify the actual quantity consumed, and so the corresponding long-term risk. However, no inverse effect of these factors which would be susceptible to counter the link to the extent of concealing it, is know for the moment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1933482 TI - Predictive value of the fluorescent cytoprint assay (FCA): a retrospective correlation study of in vitro chemosensitivity and individual responses to chemotherapy. AB - The potential clinical usefulness of the fluorescent cytoprint assay (FCA) was assessed retrospectively in 73 cancer patients by correlating individual tumor chemosensitivity in vitro with responses to chemotherapy. The data show that the FCA has a sensitivity of 98%, specificity of 81%, and predictive accuracies of 85% and 97% for positive and negative clinical responses, respectively. PMID- 1933483 TI - Measurement of sensitivity to adriamycin in hybrid spheroids. AB - Using the newly developed hybrid spheroid system, we have been able to measure sensitivities to adriamycin in two sublines of LoVo cells (a human colon adenocarcinoma line). Hybrid spheroids are composed of coagglomerated LoVo cells, and nonproliferating HeLa "feeder" cells, mimicking a population of minitumors. Spheroids of uniform size, but containing different numbers of LoVo cells, were incubated with various concentrations of adriamycin and after washing, plated for colony formation. Binomial counting statistics were achieved by marking surface attached spheroids soon after plating, and scoring colonies one week later. From the fraction of noncolony formers, the average number of clonogens per spheroid (clonogenicity) was calculated using the zero term of the Poisson distribution. The effect of treatment with adriamycin was evaluated from the decrease in clonogenicity in parallel series of hybrid spheroids. Response to treatment was found to be independent of cellular clonogenicity in the control, untreated series. Dose-response curves were obtained for each of the two sublines after treatment for 1.5 h with various concentrations of adriamycin. The difference in the response to adriamycin between the two sublines amounted to a factor of 27 (deduced from D0 ratios; these are the same as isosurvival dose ratios). PMID- 1933484 TI - A mathematical model describing consequences of abnormally high levels of epidermal growth factor receptor on the proliferation of neoplastic cells. AB - Recent laboratory and clinical data suggest that some human neoplasms exhibit unusually high levels of cell-surface receptors for epidermal growth factor, and that this abnormality is associated with rapid cellular proliferation and poor prognosis. We propose that the existence of an abnormally high number of mitogen receptors is not merely correlated with rapid proliferation but is pathophysiologically responsible for such behavior. Cells with high levels of mitogen receptors may be rendered 'hypersensitive' to mitogenic stimuli, and hence may be stimulated to divide even when ambient mitogen concentrations are at a low 'background' level, insufficient to prompt the division of cells with a normal number of receptors. To investigate this hypothesis further, we have developed a mathematical model that describes proliferative behavior of cells as a function of mitogen concentration and receptor number. The model enables us to simulate the proliferative behavior of cells with various receptor levels at various mitogen concentrations and predicts a growth advantage associated with excess mitogen receptors. Computer simulations based on the model are consistent with previously published experimental data. This work provides support for the view that overexpression of genes encoding normal growth factor receptors can contribute to the inappropriate proliferation of neoplastic cells. PMID- 1933485 TI - Intraosseous infusions: an important but forgotten method of vascular access. AB - Patients with malignancies or other prolonged illnesses such as acquired immune deficiency syndrome, require long-term vascular access. Unfortunately, currently available technologies which access the vascular system, such as intravenous catheters (external or implanted ports), have frequent complications including clotting and infection which limit their long-term usefulness. An important but forgotten method to access the central venous system is through the intraosseous route. This review summarizes past experience with the intraosseous route of access to the central venous system as well as describes a new device which might eventually make intraosseous access more convenient for the patient. It is anticipated this forgotten method of vascular access will be used more frequently in patients who have exhausted conventional venous access systems. PMID- 1933486 TI - The immunotherapy of human cancer with interleukin 2: present status and future directions. AB - Interleukin-2 (IL-2) is the principal soluble factor responsible for the proliferation of activated T cells. In animal models and humans, administration of IL-2 can induce regressions of established cancers. These antitumor effects may be partially mediated by cytotoxic effector cells activated by IL-2, including lymphokine-activated killer (LAK) cells and cytotoxic T lymphocytes. IL 2 has additional effects on other components of the cellular immune system, including B cells and macrophages, and induces secretion of other soluble mediators, including tumor necrosis factors (TNF) alpha and beta, and interferon gamma. These effects may contribute to the antitumor activity of IL-2 as well as its dose-related toxicity. Multiple Phase I and II trials have been completed or are ongoing evaluating the clinical and biological effects of IL-2 given by diverse routes and schedules, both alone and in combination with infusions of ex vivo IL-2-activated autologous LAK cells. Other studies have begun to explore the potential for antitumor synergy when IL-2 is combined with the different interferons, TNF, monoclonal antibodies, and cytotoxic drugs. The biology, toxicity, and clinical activity documented in IL-2 clinical trials to date are reviewed, and prospects for future directions outlined. PMID- 1933487 TI - Cancer invasion and metastasis: positive and negative regulatory elements. PMID- 1933488 TI - The EGF receptor system as a target for antitumor therapy. AB - Monoclonal anti-EGF receptor antibodies, EGF receptor antibodies coupled to toxins, TGF alpha-toxin conjugates and tyrosine kinase inhibitors show great potential as antitumor agents. These compounds are effective inhibitors of the EGF receptor system as it functions in the mitogenic stimulation of malignant cells. The effectiveness of cell growth inhibition mediated by anti-EGF receptor antibody and tyrosine kinase inhibitors may prove to be limited and selective. This is in view of the possibility that malignant cell proliferation may be controlled by various mechanisms instead of that which involves the EGF receptor system, despite the expression of both EGF receptor and TGF alpha in the same cell. Other growth control mechanisms could involve hormone receptor systems such as estradiol and the estrogen receptor, oncogene activation or other growth factor-receptor systems. In those malignancies in which growth control resides in the EGF-receptor system, antitumor therapy using monoclonal anti-EGF receptor antibodies and tyrosine kinase inhibitors is a possibility worth pursuing. The effectiveness of immunotoxins and TGF alpha-toxin conjugates may only require the presence of EGF receptor and not be limited to those cells whose growth is controlled exclusively by the EGF receptor system. Nonspecific toxicity may, however, limit the use of these compounds. Further studies assessing the extent of such a toxicity are in order. In the face of the preceding reservations, however, one must not overlook the potential for great achievement as this novel therapeutic avenue is traversed. PMID- 1933489 TI - The cancer survivorship movement. PMID- 1933490 TI - Alterations in self-perceptions among adolescent cancer survivors. AB - Psychosocial adjustment in adolescent cancer survivors has been documented to be quite variable. Factors mediating adjustment need to be identified. The current study is an exploration of the impact that cancer diagnosis and treatment has on adolescent's self-perceptions and the role this has in mediating adjustment in this group. Fifty-eight adolescent survivors of hematologic malignancies were interviewed about alterations in self-perceptions related to their cancer experience and completed a cancer-specific social problem-solving task. Initial findings suggest that cancer universally alters the way adolescent survivors view themselves, but that the alteration can be both positive or negative depending on the meaning ascribed to it. PMID- 1933491 TI - Employment discrimination: another hurdle for cancer survivors. AB - Approximately 25% of the six million persons 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 1991 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 a cancer survivor that are based on misconceptions about cancer, instead of the individual's ability to perform the job, may violate the survivor's legal rights. Employment discrimination against individuals who are qualified for jobs, but are treated differently solely because of their cancer histories, 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- 1933493 TI - Patients or partners? Public health policy versus the public. PMID- 1933492 TI - The off-label debate: a threat to the future of cancer care. PMID- 1933494 TI - Survivorship: beyond just a movement. PMID- 1933495 TI - Advocacy: a new role for cancer patients. PMID- 1933496 TI - Is that a bulging disk, a small herniation or a moderate protrusion? PMID- 1933497 TI - A simplified terminology for abnormalities of the lumbar disk. AB - The terminology for abnormalities of the lumbar disk has always been a source of confusion. Recent advances in pathological studies have inspired the authors to propose a simple classification of common disk anomalies suitable not only for diagnostic radiologists but also for referring clinicians. Although the diagnosis of a few pathological entities will only be possible with specific imaging techniques, the proposed classification is appropriate for reporting observations from plain films, conventional tomograms, myelograms, diskograms, computed tomography scans and magnetic resonance images. All lumbar disks can thus be classified into one or more of the following categories: normal, aging, scarred, ruptured and herniated. A disk herniation is defined as a localized exit of disk material beyond the limits of the original intervertebral space. PMID- 1933498 TI - Emergency excretory urography in blunt abdominal trauma. AB - In a prospective study the authors correlated the degree of hematuria and of blunt abdominal trauma with the results of emergency excretory urography. Urograms were obtained for 37 patients who presented with blunt abdominal trauma, no gross hematuria and at least five erythrocytes per high-power field (hpf) on microscopic urinalysis. Microscopic hematuria was defined as an erythrocyte count of more than 5 and fewer than 50 per hpf. Major trauma was defined as shock (systolic blood pressure of less than 90 mm Hg), fracture of the lumbar spine, the pelvis or the lower ribs, ecchymosis in the flank or acute abdominal injury. Contusions and small subcapsular hematomas were defined as nonsignificant renal injuries; all other renal injuries were defined as significant. Of 17 patients with minor blunt abdominal trauma 14 had fewer than 50 erythrocytes per hpf; none of these had a significant renal injury, whereas 1 of the 3 with more than 50 erythrocytes per hpf did have a significant injury. Of 20 patients with major trauma 5 had a significant renal injury. The authors conclude that microscopic hematuria associated with blunt abdominal trauma but without shock or major nongenitourinary injury does not warrant routine excretory urography. PMID- 1933499 TI - Multiple intracerebral cavernous angiomas. AB - Eight patients (seven women and one man) with multiple intracerebral cavernous angiomas (cavernomas), also known as angiomatosis cerebri, were examined with high-field magnetic resonance imaging (MRI). Although previous articles have referred to such cases, a series similar to the one reported here has apparently not been described in the radiology literature. The patients presented with seizures, progressive neurologic deficit or cerebral hemorrhage. In all eight cases the multiplicity of the lesions was an incidental finding in the magnetic resonance images. The MRI appearance of the cavernomas, although characteristic, is similar to that of other angiographically occult intracranial vascular malformations, in particular thrombosed arteriovenous malformations and mixed vascular malformations, as well as that of hemorrhagic metastases. Additional criteria, such as the absence of edema, the presence of calcifications and the temporal evolution of the cavernomas on serial scans, should allow cavernomas to be differentiated from hemorrhagic metastases. The exquisite sensitivity in detecting angiomatosis cerebri and the ability to show the evolution of internal hemorrhage in individual lesions make MRI the method of choice for diagnosing and following this condition. PMID- 1933500 TI - Magnetic resonance imaging of hypothalamic hamartomas causing gelastic epilepsy. AB - Hypothalamic hamartomas may cause a peculiar epileptic syndrome characterized by seizures of laughter and precocious puberty. Four mentally handicapped patients suffering from gelastic epilepsy were referred to our institution for investigation; three of them also presented with precocious puberty. In all four cases magnetic resonance imaging (MRI) revealed a space-occupying lesion of the hypothalamus that was considered to be a hamartoma. Biopsies were not performed. Hamartomas appear isodense in plain computed tomography scans, and they do not enhance. Such lesions display an isointense signal in T1-weighted magnetic resonance images and a hyperintense signal in proton density and T2-weighted images. MRI is the procedure of choice for detecting such lesions at the base of the brain. PMID- 1933502 TI - Radiologic features of congenital transverse deficiency of the forearm. AB - The records of fifteen patients (11 girls and 4 boys) with a congenital transverse deficiency of the forearm were studied. In 11 patients the lesion was on the left. The deficiency occurred in the proximal third of the forearm in 13 patients. The radius and the ulna were usually bowed, and their shafts were sometimes irregular. The radial head was dislocated in six patients, and minor abnormalities occurred in the distal humerus in five and the proximal ulna in five. PMID- 1933501 TI - Fracture and posterior dislocation of the os peroneum associated with rupture of the peroneus longus tendon. AB - Subcutaneous rupture of the peroneus longus tendon occurring through a fracture of the os peroneum (OP) or secondary to posterior dislocation of this uncommon sesamoid bone is rare. The authors report three incidents of this injury, which presented either as fracture of the OP with diastasis of the fragments or as posterior dislocation of the whole OP without fracture. In all cases conservative treatment yielded satisfactory results. It is emphasized that, in all cases of ankle injury, radiologists should carefully examine the plain radiographs because most OP injuries are not seen in images obtained at the time of injury and are discovered retrospectively when the fragments separate. Not treating the problem at an early stage may lead to instability of the ankle or to peroneal compartment syndrome. PMID- 1933503 TI - Comparison of transvaginal and transabdominal ultrasonography in ectopic pregnancy. AB - The authors retrospectively reviewed 45 consecutive cases of proven ectopic pregnancy for which both transvaginal (TV) and transabdominal (TA) ultrasonography had been performed to compare the diagnostic efficacy of the two imaging techniques. The criteria for a diagnosis of ectopic gestation included an extrauterine gestational sac containing a fetus or a fetal pole, or an empty extrauterine sac. Solid or complex adnexal masses with evidence of hemoperitoneum were considered suggestive but nondiagnostic. TV ultrasonography was superior to TA ultrasonography in 22 cases (49%) and inferior in 3 (7%). In the remaining 20 cases (44%) the two methods yielded similar information. For cases in which TV ultrasonography was superior, this method provided clear evidence of ectopic pregnancy in 11 cases in which TA ultrasonography demonstrated nonspecific masses or normal adnexa; in the other 11 cases both methods led to the correct diagnosis, but TV ultrasonography provided additional useful information. The authors conclude that TV ultrasonography has a definite role in improving the diagnosis of ectopic pregnancy. PMID- 1933504 TI - Diffuse metastatic involvement of the breast. AB - Metastases to the breast are not very common and, according to the recent literature, usually present as nodules, most often single but sometimes multiple, generally without retraction or thickening of the skin. The authors reviewed 21 such cases from the last 15 years. In six patients the metastatic infiltration presented as diffuse thickening of the skin and increased density of the breast, as can be seen in inflammatory diseases or after radiotherapy. In five of these six women lymphangitic spread of the carcinoma was demonstrated by microscopy. PMID- 1933505 TI - Prenatal ultrasonographic diagnosis of dicephalus conjoined twins. AB - The authors report the prenatal diagnosis by ultrasonography of dicephalus dipus dibrachius conjoined twins (with two heads, one body, two legs and two arms) at 31 weeks' gestation. They discuss the types of conjoined twinning and their frequency of occurrence and the criteria for prenatal diagnosis, and they offer recommendations for management. PMID- 1933506 TI - Osteolysis of the calcaneus in a child with localized scleroderma. AB - In a young girl with localized scleroderma a circumscribed area of lysis developed in the calcaneus beneath the involved skin and soft tissues of the foot. A biopsy revealed vascular changes characteristic of scleroderma associated with infarction and severe resorption of the bone. A geographic pattern of bone destruction in a child with localized scleroderma has not previously been reported. PMID- 1933508 TI - Answer to case of the month #9. Histiocytosis X. PMID- 1933507 TI - Patient with miliary nodules and diarrhea. PMID- 1933509 TI - [Effects of neutron-gamma or gamma irradiation on plasma coagulation factors. Effect of a substitution treatment]. AB - Neutron-gamma irradiation of the baboon at lethal dose altered the plasma clotting factors and induced a fibrinoformation alteration which occurred shortly before death. These disturbances, which were not found after gamma irradiation, could explain the importance of the haemorrhagic syndrome. Treatment by P.P.S.B. (factors II, VII, X and IX) counteracted the alterations of the plasma clotting factors, but had no influence on the lethality nor on the fibrinoformation alteration which seems to be an important cause of death. PMID- 1933510 TI - [Nutritional regulation of serum osteocalcin: study in kwashiorkor]. AB - The serum levels of osteocalcin (bone gla protein) in two groups of Senegalese children, healthy controls and severely malnourished (kwashiorkor) children during nutritional rehabilitation, were measured. The serum osteocalcin of all kwashiorkor children was dramatically decreased on admission to hospital, but increased fourfold during rehabilitation. Serum osteocalcin was low in the control group. In both groups these low levels seemed to be independent of those of 1,25-dihydroxyvitamine D3 which were in the normal range. The results suggest that serum osteocalcin levels might be related to protein-energy status. PMID- 1933511 TI - [Purification and characterization of presumed thyrotropic hormone subunits of a teleost fish, the eel (Anguilla anguilla)]. AB - We have only a partial knowledge of fish thyrotropins (TSH) and no data about peptide sequence are available. Various HPLC techniques allowed us to purify a 31.4 kDa, heterodimeric protein from saline eel pituitary extracts containing TSH activity. Partial N-terminal sequence (24 amino acids) from one subunit was strictly identical to that of eel gonadotropin II (GTH II) alpha subunit. With regard to the second subunit, 41% of the 22 amino acids identified at the N terminus were homologous to those of bovine beta TSH and 36% were homologous to those of eel beta GTH II. Thus, the purified protein exhibits biochemical characteristics similar to those of mammalian TSH, in particular an alpha subunit common with GTH. PMID- 1933512 TI - Effect of magnesium on the growth and cell cycle of transformed and non transformed epithelial rat liver cells in vitro. AB - The effects of magnesium (Mg) restriction on cell growth and the cell cycle were determined in transformed (TRL-8) and non-transformed (TRL-12-15) epithelial-like rat liver cells. Cells were cultured in RPMI 1640 medium in which the Mg concentration was reduced to 0.5, 0.1, and 0 x the concentration in the regular RPMI 1640 media (100mg/l). Cell growth in the transformed cells was not influenced by the Mg restriction as greatly as in the non-transformed cell line. Transit through the cell cycle also exhibited an independence of the Mg in the medium in the transformed cells. When transformed cells were grown for two generations in Mg-limited medium, the growth rate slowed to a rate similar to that demonstrated by the non-transformed cells. Analysis by flow cytometry showed that transit through the cell cycle was minimally slowed in Mg deficient transformed cells; however, transit through the G1 and S phases in the non transformed cells was slowed. The TRL-8 cells in Mg-limited medium resulted in fewer nuclei in G1 with subsequent increases in the percentages of S-phase nuclei. The TRL 12-15 cells reacted oppositely with the number of G1 nuclei increased and the number of S-phase nuclei decreased. In respect to growth, these results show that epithelial cells respond in a similar manner to Mg-limitation as do fibroblast cells. The transformed cells exhibited a level of independence from Mg in respect to growth, reproduction, and cell-cycle kinetics. PMID- 1933514 TI - Regeneration of acetylcholinesterase in clonal neuroblastoma-glioma hybrid NG108 15 cells after soman inhibition: effect of glycyl-L-glutamine. AB - Acetylcholinesterase (AChE) in the clonal NG108-15 cell line has been previously characterized. This cell line represents an in vitro system to study AChE regulation and effects of chemical compounds that may alter AChE activity. Recently, glycyl-L-glutamine (GLG) was demonstrated to function as a neurotrophic factor for maintenance of AChE content in cat denervated superior cervical ganglion cells. In the present study, regeneration of AChE activity in cultures of undifferentiated NG108-15 cells after soman inhibition was investigated in the presence and absence of GLG. Cells were treated with soman (5.5 x 10(-6) M) for 15 min and then washed to remove excess soman. Culture medium containing either GLG (10(-6), 10(-5), or 10(-4) M) or glycyl-L-glutamic acid (10(-6) M) was added to cultures after soman treatment and remained in the medium until cell harvest. Cells were physically detached at various times after soman treatment and specific AChE activity was determined. After soman, AChE activity dramatically decreased to less than 1% of untreated cellular activity at 1 hr. AChE activity gradually increased after 5 hr, while untreated cell AChE activity was regained 20 hr after soman. The t1/2 for AChE regeneration was approximately 10 hr. GLG did not increase the rate of AChE regeneration after soman inhibition. These results indicate that GLG is not a directly acting neurotrophic factor for AChE synthesis in NG108-15 cells after chemical AChE inactivation. PMID- 1933513 TI - Comparative study of intracellular glutathione content in rat lymphocyte cultures treated with 2-mercaptoethanol and interleukin-2. AB - The level of intracellular glutathione (GSH) in mitogen-stimulated mouse lymphocytes is increased in the presence of 2-mercaptoethanol (2-ME), an enhancer of lymphocyte activation and proliferation. Since proliferation of lymphocytes in response to mitogens involves direct activation by a mitogen followed by continued proliferation in response to interleukin-2 (IL-2), we have investigated the effect of 2-ME and exogenous IL-2 on the GSH content and cell proliferation of rat lymphocytes stimulated with phytohemagglutinin (PHA). PHA stimulation increased both GSH content and the magnitude of the proliferative response, as measured by thymidine incorporation into cellular DNA. However, incubation of stimulated lymphocytes with 2-ME or IL-2 for 72 hr produced a significant further elevation of GSH levels and thymidine incorporation. 2-ME also increased the GSH content in unstimulated cultures, but it had little effect on thymidine incorporation. IL-2 increased GSH content and decreased thymidine incorporation in unstimulated lymphocytes. Exposure of cells to DL-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of GSH biosynthesis, significantly depleted GSH and lowered the proliferative response, suggesting a crucial role of de novo GSH synthesis for lymphocyte activation. The data suggest that both 2-ME and IL-2 promote lymphocyte proliferation, although the mechanisms by which intracellular GSH levels are increased by the agents are apparently different. PMID- 1933515 TI - Effect of sulfur exposure on protease activity in human peripheral blood lymphocytes. AB - Sulfur mustard is a chemical warfare blistering agent for which neither the mechanism of action nor an antidote is known. Papirmeister et al. (1985) have postulated a biochemical hypothesis for mustard-induced cutaneous injury involving a sequelae of DNA alkylation, metabolic disruption and activation of protease. Human peripheral blood lymphocytes in cell cultures were employed as an in vitro model for alkylating agent toxicity. A chromogenic peptide substrate assay was used for detection of protease in lymphocytes treated with sulfur mustard or chloroethyl ethyl sulfide. Exposure of human peripheral blood lymphocytes from normal donors to these alkylating agents resulted in an increase in cell associated protease activity. This increase in protease activity may contribute to the pathology or act as an indicator to predict methods of therapeutic intervention for sulfur mustard toxicity. PMID- 1933516 TI - Buthionine sulfoximine induced growth inhibition in human lung carcinoma cells does not correlate with glutathione depletion. AB - Treatment of A549 human lung carcinoma cells with L-buthionine-[S,R]-sulfoximine (BSO) results concomitantly in cellular glutathione (GSH) depletion and growth inhibition. The nature of BSO effects on cell growth and the relationships between BSO inhibition of cell growth and BSO effects on cellular GSH levels were determined in this study. A dose dependent effect of BSO on cell growth was observed, but this effect was found not to correlate with BSO effects on cellular GSH levels. Treatment with BSO for 60 h at concentrations of 5 and 10 mM was found to deplete cellular GSH at similar rates and to an undetectable level (below 0.5 nmol/mg protein). However, cessation of growth occurred in 10 mM BSO whereas growth continued at better than one half the control rate in 5 mM BSO. The results suggest there may be a distinct threshold level of intracellular GSH (on the order of or less than 0.5 nmol/mg protein) required for cell growth and for cells to protect themselves from the antiproliferative effects of BSO. At a concentration of 10 mM, BSO inhibited both DNA and protein synthesis and arrested growth of A549 cells throughout rather than at a specific phase of the cell cycle. BSO inhibition of growth was not, as indicated by colony-forming efficiency (CFE) and electron microscopy studies, accompanied by indications of cytotoxic effects. A stimulatory effect of 0.1 mM BSO on the growth of A549 cells was found also. PMID- 1933518 TI - 1986 survey of genetic toxicology testing in industry, government contract, and academic laboratories. AB - Results of the 1986 Genetic Toxicology Association's survey of industrial, government, contract, and academic laboratories on the status of several assays in genetic toxicology are presented below. 1. The most commonly used assay was the Salmonella typhimurium/mammalian microsomal (Ames) assay, which was used by 83% of all respondents. 2. The next five (5) most commonly used assays were in vitro cytogenetics (72%), in vivo cytogenetics (59%), CHO HGPRT gene mutation (55%), the micronucleus assay (53%), and L517BY gene mutation (45%). 3. The assay showing the greatest percentage increase in routine use was the micronucleus assay which went from 14% in 1984 to 34% in 1986, an increase of 20%. 4. Other assays which increased in routine use were CHO HGPRT mutation (+18%); in vitro cytogenetics (+14%); L5178Y gene mutation (+9%), and the Ames assay (+5%). 5. Routine use of in vitro UDS assays declined by 6%; use of in vitro SCE assays declined by 12%. 6. There was no change in the rate of routine use of in vivo cytogenetics or in vivo SCE assays. 7. Assays routinely performed on contract included the Salmonella assay, CHO HGPRT gene mutation, in vitro cytogenetics, in vitro UDS, in vivo cytogenetics, the micronucleus assay, L5178Y gene mutation, and the Drosophila sex-linked recessive lethal assay. 8. Four assays were being developed by five or more laboratories. These included in vitro SCE (8); the micronucleus assay (7); in vivo SCE (6); and DNA adduct formation (5). 9. A total of 17 assays had been abandoned by one or more laboratories. However, since no assay had been given up by more than three laboratories no conclusions can be drawn about the overall robustness of any of the assays on the survey form. PMID- 1933519 TI - [The effects of administering surfactant to two adolescents with leukemia suffering from respiratory distress]. AB - Two adolescents (12 years old, suffering from acute lymphoid leukaemia (LLA) and 16 years old with acute myeloid leukaemia (LMA)) were treated with porcine surfactant (Curosurf). The indication for this treatment was a severe Respiratory Distress Syndrome (RDS) which appeared during leukaemia treatment. Pulmonary thrombo-embolism was suspected. The surfactant administered improved ventilation and oxygenation, enabling confirmation of the diagnosis which would otherwise have been impossible due to the seriousness of their condition. PMID- 1933520 TI - [Comparative trials of fluid gelatins on hemostasis in heart surgery in adults]. AB - The purpose of this study was to compare, in adult cardiac surgery, the results of two gelatin substitutes (Plasmion and Haemaccel) especially for haemostasis and coagulation factors. Patients showing before operation any perturbation of blood parameters (anaemia, coagulation troubles) as well as patients suffering from serious complications or deceased in the postoperative period have been excluded. This study was realised with 54 patients randomised in two groups: group P (Plasmion); group H (Haemaccel). Anaesthesia was a diazanalgesia. Hemodilution was used in combination with autologous peroperative blood transfusion and reinfusion of residual blood from ECC after ultrafiltration. The two groups were statistically similar. In average, patients received the same gelatins quantity. The only remarkable findings were: a lesser decrease of platelets number per-ECC: a lesser fibrinogen level in postoperative period with Haemaccel. PMID- 1933517 TI - HgCl2-induced alteration of actin filaments in cultured primary rat proximal tubule epithelial cells labelled with fluorescein phalloidin. AB - When proximal tubule epithelial cells are exposed to HgCl2, cytoplasmic blebs are formed. These represent an early, potentially reversible response to injury. These blebs are accompanied by reorganization of cytoskeletal proteins, and presumably by alternations in cytoskeletal-plasma membrane interactions. Ca(2+) activated proteinases, such as calpain, are known to affect cytoskeletal proteins and to be involved in diverse cellular processes. However, the role of calpains in cytotoxicity due to HgCl2 is unknown. To determine the relationship between F actin, calpain, and HgCl2 toxicity, cells were stained with fluorescein phalloidin before and after treatment with HgCl2. Cells were grown on coverslips and exposed to HgCl2 (10 or 25 microM) in the presence or absence of the calpain inhibitor, leupeptin. Untreated cells were flat, polygonal, and contained many fluorescent-stained cables of actin filaments. Generally, cells exposed to HgCl2 became pleomorphic and contracted as the blebs formed. These cells showed fewer actin cables and fluorescence was seen mostly as either compact areas of dense stain or as peripheral rings. In many cells, actin cables and filaments were completely absent. Disappearance of F-actin was initially seen by 2 min after exposure to HgCl2. Thus, disruption of the actin cytoskeleton and blebbing were found to be early events in HgCl2 toxicity. When leupeptin was used with HgCl2 treatment, the actin staining appeared similar to that of untreated cells. PMID- 1933521 TI - [Complications of local and regional anesthesia. An analysis of closed files of insurance companies]. AB - We report a review of closed insurance claims for local and regional anaesthesia mishaps in the main private professional insurance companies. Twenty eight cases with extensive written documentation were discovered, spanning a 6 years interval between 1983 and 1989, involving 21 epidural, 6 spinal and 1 caudal anaesthesias, half with surgical and half obstetrical indication, and excluding all other blocks. Twenty four out of the 28 patients were relatively healthy. ASA I or II, only 4 ASA III. They fitted 4 items of our taxonomy of known complications: 15 cardiac arrests, 10 neurological damages, 1 systemic toxic reaction to local anaesthetic drug and 1 allergic reaction to dextran. The cardiac arrests resulted primarily from the 3 following or contributing factors: hypovolemia (in 3 cases), added sedation (7) and high or total spinal block following reinforcing doses (8). Twenty two had a poor outcome: 8 deaths, 7 severe neurological injuries, a baby was dead and another child had severe neurobehavioral sequellae. The author points out the limitation of this study--a biased sample of all adverse events and inability to derive an incidence. However some of these events reveal patterns of anaesthetic management which lead to poor outcomes. PMID- 1933522 TI - [Spinal anesthesia in ambulatory anesthesia of the infant]. AB - Two hundred spinal anesthesias have been performed in infants for abdominal surgery, thirty of which for day surgery. Intrathecal injection of 0.5% bupivacaine solution is realised in good conditions, sometimes with narcosis complementation (ketamine or halothane). Motor block takes place without delay and lasts for an average of 95 +/- 25 minutes. There is no hemodynamic disturbance. This technic could be used in day surgery by reason of quick recovery. PMID- 1933523 TI - [The importance of the preoperative measurement of hemoglobin concentration. Evaluation of a colorimetric method (Hemocue)]. AB - The present study compares two methods of haemoglobin measurement during surgery in 40 patients aged 1 to 85 years. The reference method is the Coulter STKS based on red cell count and mean cellular content in haemoglobin measurement. The method tested (Hemocue-Diagnostics Transfusion) allows instantaneous determination of haemoglobin on a 10 mu sample by measuring infrared absorption by haemoglobin in the 565 and 880 nm wavelengths. These methods have been compared using the method of assessment of agreement described by Bland and Altman. As previous reports suggested that the precision of haemoglobin measurement by Hemocue could depend on the capillary or venous site of sampling, we assessed agreement of the two methods of measurement of haemoglobin at both sites. In addition, the relationship between hematocrit and haemoglobin measured by either method has been assessed. On venous samples, there was a good agreement between the two methods of measurement of haemoglobin (n = 47), with a mean difference of -0.166 g/dl-1 and agreement limits of -1.041 g/dl-1 and +0.195 g/dl 1. Ninety six percent of the observed differences to two methods were within the 95% confidence interval. On capillary samples, there was a poor agreement between Hemocue and Coulter since the mean difference was -0.272 g/dl-1 with the following limits of agreement: -2.356 g/dl-1 and +1.812 g/dl-1. Only 92% of the observed differences were within the 95% confidence interval, with 17% of these being greater than the clinically accepted limit of 1 g/dl-1. The precision of Hemocue measurement of capillary blood haemoglobin was only +/- 16%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933524 TI - [Pollution of operating rooms. Measurements made during five anesthesias]. AB - The purpose of this study is to measure amounts of anaesthetic vapours present in operating rooms and anaesthetic places without any gas scavenging system except air conditioning with fifteen air changes per hour. Nitrous oxide, halothane and isoflurane were measured. Halothane and isoflurane concentration is slightly higher than the French standard for anaesthetic places and lower for operating rooms. Nitrous oxide concentration is five to eight times greater than recommended standard. Although no international agreement exists concerning an acceptable pollution standard, it seems that only nitrous oxide pollution is disquieting. It would seem sensible to avoid needles contamination by use of waste gas scavenging devices. PMID- 1933525 TI - [Anaphylactoid shock due to metabisulfites during cesarean section under peridural anesthesia]. AB - Sulfiting agents are antioxidants widely used in both food and pharmaceutical industries. They have been identified as responsible for adverse severe reactions. A case is reported of anaphylactoid shock during epidural anaesthesia for caesarean section. The responsible agent was metabisulfite, additive agent of local anesthetics containing epinephrine. PMID- 1933527 TI - [The value of preanesthetic consultation. Apropos of a case]. PMID- 1933526 TI - [Nitrate derivatives and anesthesia-resuscitation: physiopathologic bases and therapeutic indications]. AB - This review briefly describes the cellular mechanisms of nitrates and the tolerance. Nitrates activate NO production thus GMPc in the smooth muscle cell explaining their vasodilating properties even in absence of an intact endothelium. The biologic pathway of AMPc is stimulated by prostaglandin activated by nitrates. Tolerance to these agents could result from depletion of sulfhydryl radical but also from reflex cardiovascular adaptation. After a brief recall of pharmacokinetic, pharmacodynamic properties are detailed. Therapeutic use in cardiac surgery, non-cardiac surgery, controlled hypotension, aortic surgery, heart failure, unstable angina, myocardial infarction and systolic hypertension in the elderly are discussed. PMID- 1933528 TI - [Formation of a knot in a J spiral metallic guide: a complication of the Seldinger method]. AB - Central venous catheter insertion by Seldinger's technique uses a wire guide which could be cause of complications. This case reports a blocked wire guide of which J tip was responsible for knotting. Utilization of vessel dilator of central venous catheterization set (Arrow) permitted to liberate and withdraw the wire guide without surgical operation. A larger use of this wire guide could increase the frequency of such complications. PMID- 1933529 TI - [Spinal cord injury and secondary autonomic function disorders]. AB - Autonomic dysfunction is frequently reported after high level spinal cord injury. These disorders usually occur in the first days and resolve spontaneously within 3 to 6 weeks. Usual clinical aspects are hemodynamic abnormalities and often bradycardia which can lead to death. These dysfunctions rarely reappear during neurological status recovery. In this case report, usual autonomic disorders were noted after a T5 level spinal injury with partial motor lesions. However during motor recovery periods, arrhythmias occurred, including ventricular extrasystoles and bursts of ventricular tachycardia. Physiopathological mechanisms are discussed and regulation changes of sympathetic and parasympathetic autonomic nervous system are evoked. PMID- 1933530 TI - [Acute adult respiratory distress syndrome in leptospirosis]. AB - The respiratory manifestations of leptospirosis are usually benign. A case is reported of leptospirosis with serious pulmonary affection. Pulmonary involvement in leptospirosis is infrequently predominant and usually without bearing on prognosis. Clinical and roentgenological features are reviewed. Severe forms with massive hemoptysis or acute respiratory failure occur occasionally. The clinical symptoms, the radiological manifestations and haemodynamic investigation were suggestive of an acute respiratory distress by non haemodynamic pulmonary oedema. In accordance with other authors, one could be justified in including this acute respiratory failure as part of the adult respiratory distress syndrome. Since leptospirosis has extremely diverse clinical features, physicians should have this diagnosis in mind in many circumstances and should request the appropriate examinations at the right moment. Carefully performed microbiological techniques may reduce the problems encountered in isolating leptospires. Serological tests requested after the 12th day of the disease and repeated several times should improve the diagnosis confirmation. The potential severity of certain forms justifies curative antibiotic therapy. PMID- 1933531 TI - [Acute pancreatitis: evaluation of two years of a diagnostic and therapeutic protocol]. PMID- 1933532 TI - Nutrition and cancer: current status. PMID- 1933533 TI - American Cancer Society guidelines on diet, nutrition, and cancer. The Work Study Group on Diet, Nutrition, and Cancer. PMID- 1933534 TI - Cancer of the breast in men. AB - As knowledge grows about breast cancer in men, it becomes apparent that the disease is strikingly similar to that seen in women. Although rare, as is cancer in most vestigial organs, all indications are that it shares a common etiology and a similar natural history with breast cancer in females and that apparent differences between the diseases in the two sexes are minor or illusory. The poor prognosis of men in the past promises to yield to better public and professional education about the value of prompt recognition and treatment. Fortunately, the lessons learned from treatment of women are also applicable to men, and in comparable stages men prove equally curable. PMID- 1933535 TI - Questionable methods of cancer management. Immuno-augmentative therapy (IAT). AB - "Immuno-augmentative therapy" is a method of cancer management developed by Lawrence Burton, PhD. Dr. Burton states that IAT can control all forms of cancer by restoring natural immune defenses. He claims to accomplish this by injecting protein extracts isolated with processes that he has patented. However, experts believe that the substances he claims to use cannot be produced by these procedures and have not been demonstrated to exist in the human body. He has not published detailed clinical reports, divulged the details of his methods, published meaningful statistics, conducted a controlled trial, nor provided independent investigators with specimens of his treatment materials for analysis. During the mid-1980s, several cases were reported where patients of Dr. Burton developed serious infections following IAT. PMID- 1933536 TI - Cancer of the larynx. PMID- 1933537 TI - Mammography. PMID- 1933538 TI - Surgical management of breast cancer. PMID- 1933539 TI - Lung cancer and smoking. PMID- 1933540 TI - Microcirculation: an open area for nursing research. PMID- 1933541 TI - Needs of family members of patients in the intensive care unit over time. PMID- 1933542 TI - Nursing care of the patient undergoing combined kidney-pancreas transplantation. PMID- 1933543 TI - Planning and operation of a critical care pharmacy satellite. PMID- 1933544 TI - Steroid psychosis and hepatic encephalopathy in liver transplant patients: which is which and what do you do? PMID- 1933545 TI - Communication, decision making, and perception of nursing roles in a pediatric intensive care unit. PMID- 1933546 TI - Forensic nursing in the emergency department: a new role for the 1990s. PMID- 1933547 TI - Pharmacologic management of ventricular arrhythmias. PMID- 1933548 TI - The effect of supplier inducement on Norwegian dental services; some empirical findings based on a theoretical model. AB - The aim of the present study was to ascertain whether the amount of dental care demanded and the amount of dental care received in Norway were influenced by supplier inducement. There is a fixed price schedule for dental care in Norway, which establishes the framework for the theoretical model on which the empirical studies were based. The model has been developed by Birch (1988), and it describes how the utilisation of dental services may be influenced both by supplier inducement and reduced shadow prices (access costs) when the population to dentist ratio decreases. The sample of 1200 individuals was representative of the non-institutionalised Norwegian population aged 20 years and over. Variables measuring access costs, rationing of care, oral health, unmet need, family income and socio-demographic characteristics of the population were included as control variables. Supplier inducement effects were found on dentist-initiated visits, and on the cost per visit. It was concluded that dentists in areas of excess supply were able to maintain their workload by increasing the demand for and the utilisation of their services. Also, that the existing maldistribution of dentists between the northern and southern parts of Norway is not likely to be altered by allowing market mechanisms to operate on the dental care market. PMID- 1933549 TI - Tooth surface loss among people exposed to cement and stone dust in the work environment in Tanzania. AB - The effect of cement and stone dust on teeth was explored in a cross-sectional study, using blind dental examinations. The sample consisted of 36 workers who had been exposed to to the dust and 62 control workers. Tooth surface loss was observed in 72.2 per cent of the exposed workers and in 48.4 per cent of the controls (P less than 0.03). In both the maxillae (P less than 0.001) and the mandible (P less than 0.02) the amount of tooth surface loss was greater in the exposed workers than in the controls. Both anterior and posterior teeth were affected. These findings indicate that tooth surface loss caused by work-related dust should be considered an occupational hazard. PMID- 1933550 TI - CPITN assessments in institutionalised elderly people in Kitakyushu, Japan. AB - A CPITN survey was conducted on 1958 institutionalised elderly people aged 59 years and older at 29 of the 30 public and private institutions in the city of Kitakyushu, Japan. About 60 per cent of the sample was edentulous, and the prevalence of periodontal conditions was high. The percentages of dentate subjects with healthy gingivae, bleeding on probing, calculus, shallow pockets, and deep pockets were 3, 4, 32, 52, and 9 per cent respectively. Half the sextants in the dentate subjects were scored as excluded (less than two teeth), indicating that many teeth were missing. Only very few sextants were healthy. These findings indicate the importance of preventive programmes for periodontal diseases in the younger generations, because (a) dental care for the elderly population becomes more difficult with increasing age and (b) periodontal care, if it is available at all, is provided too late for most people. PMID- 1933551 TI - The World Health Organisation goals for oral health: a progress report. AB - Global oral health goals for the year 2000 were adopted in 1981 by the World Health Organisation. A literature review and collation of available data relating to progress towards these goals have been carried out. Their appropriateness and value as measures of oral health and disease trends are discussed. The general conclusions of the study were that the concept of global goals was valuable but that the lack of standardised data collection and publication made it difficult to evaluate progress towards attainment of the goals. PMID- 1933552 TI - Advocacy; the Leeds experience. AB - The full version of this paper was first presented at the Spring Scientific Meeting of the British Association of Community Dentistry. This short communication concerns only that part of it that dealt with the recent interpretation of the 'advocacy' concept in Britain, with the establishment of Leeds City Council Patient's Advocacy Service as its unique manifestation. A case history is presented to illustrate the confusion between the functions of the advocate and those of the traditional interpreter/link worker. Issues which arose from the development of the service are also discussed. PMID- 1933553 TI - [Analysis of occlusion and stability in complete dentures]. AB - The prosthetic treatment of edentulous patients must be carried out with the dual objective of preserving the residual ridges and re-establishing the functional activities of the masticatory system. The authors propose to investigate the subjective efficiency of the prosthesis by an interview of the patients, and the objective efficiency by clinical testing, after one year of use. In this study, a group of 41 patients, males and females, are supplied with bimaxillary full dentures according to GERBER's technique. Special attention is given to the teeth position in relation to the base stabilisation surface. The teeth likely to unbalance the prostheses were not mounted. The inter-maxillary relationship at the horizontal level was obtained by using a gothic arch recording. After one year of use, the following results were obtained: patients very satisfied with their upper denture: 43.9%; patients very satisfied with their lower denture: 39%; satisfied: 51% for the upper denture; satisfied: 56.1% for the lower denture; not satisfied: 4.9% for the two dentures. Only 12 patients (29.2%) had all of their posterior teeth put in. The decrease in the number of teeth did not reveal any significant decrease in the mastication efficiency, according to the patients opinion (2.4%). The original occlusion was restored in 78% of the cases. The authors emphasized the importance of the occlusal relationship and of the posterior teeth for stability and efficiency in the treatment of edentulous patients. PMID- 1933554 TI - [Removal of an anatomic post]. AB - Removing an anatomical cast post requires many precaution and, in most situation, gives very good results. Nevertheless, this procedure can be dangerous for the tooth or the surrounding tissues and must be considered only in case of absolute necessity. Two techniques are described using a little hole made in the coronal part of the core. A threaded wire is driven through this hole making possible the use of a crown remover. For the second technique the use of an original appliance, the ATD bridge remover, is demonstrated with very good results too. PMID- 1933555 TI - [Elastomers and peripheral seal in complete maxillary dentures]. AB - First the various physical factors involved in retention are discussed. Adhesion is designed by the Gibert formula: [formula: see text] bringing the notion of interfacial surface delimited by the fluid meniscus (epsilon) and the thickness of the salivary film at the site of formation of the meniscus (h). Atmospheric pressure plays a role by the formation of a periphery seal ensuring the creation of a depression of the interfacial fluid in order to oppose the forces of pulling. As a summary, it is important to achieve the formation of a salivary meniscus: with the smallest curvature; continuous despite the mobility of the mucosa; beyond the limit between the free mucosa and the attached mucosa and the "farthest" possible from this area. The purpose of recording the periphery borders is to obtain the highest and widest possible denture flanges without any over-extension or over-thickness. The authors then propose performing a comparative study of the various materials available for recording the periphery of maxillary full dentures, in order to determine which best responds to the criteria of quality mentioned. Several recording techniques are possible, depending on the material used: either a segmented border recording (widely described); or a recording of the periphery seal in one or several stages which is then illustrated by the use of Impregum. For each patient, recordings of the periphery was made according to a protocol always identical and precise; only the material used for this purpose (Kerr compound, regular Neo-Plex and Impregum) varied. The measure taken from these recordings showed that Impregum demonstrates the highest and thickness borders as opposed to Neo-Plex and Kerr compound which provided intermediary results. Thus, Impregum appears to be the material of choice for the optimal recording of the functional periphery seal in maxillary full dentures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1933556 TI - [An original rehabilitation method for the totally edentulous based on Ludwig's technique. 4. Articulator transfer. Mounting of artificial teeth]. AB - Balanced occlusion is the occlusal concept used in full dentures. In this article, which describes the technique for mounting teeth according to LUDWIGS, the authors present a very typical equipment (guide punch, tooth guide, positioning and mounting plates...). This provides the dental technician with all the possibilities to create occlusal curves which are individualised for each case in order to achieve a balanced and rational mounting of artificial teeth. PMID- 1933557 TI - [Preprosthetic orthodontic preparation and Branemark implants]. AB - The patient presented an important bone loss in the edentulous area 21 to 23. The 11 had a temporary crown and a removable prosthesis has replaced the anterior missing teeth. The orthodontic treatment of this class II division 1 was to be undertaken in order to reduce the maxillary proalveolie and to line up the mandibular incisors. The difficulty of the orthodontic treatment was due to the importance of the anterior edentulous area which did not allow a continuous multiring treatment but a bilateral one and a succession of anterior removable prosthesis as anchoring points. The temporary crowns on osseointegrated fixtures replacing 22 and 23 were used to obtain the final orthodontic movements needed in the orthodontic preprosthetic treatment. However, if the fixtures had been placed at the beginning of the treatment in order to use them among other anchoring points, the complete orthodontic treatment would have been faster and much easier. At that time, our major handicap was to determine the ideal position of the fixtures which would allow the orthodontic application as well as a successful cosmetic fixed prosthesis. The use of scanner, three dimensional reconstruction Scanlam, surgical stents and fixed prosthesis with inlay cores would have brought the solution to this problem. Today, the use of osseointegrated fixtures can be applied in much more complex orthodontic movements. PMID- 1933558 TI - [Surface properties of resins used for removable dentures]. AB - The comparative study of the gingival aspect of dentures made from different flasking procedures, using scanning electronic microscopy, permits the differences in the surface texture of the resins to be assessed. This surface texture will show specific aspects for each technique. The Futurajet resin presents a surface texture with cracks of 100 microns to 200 microns long and 5 microns wide. The appearance of the polymer pellets reveals a good cohesion amongst them. The Futuracryl 2000 resin has an overall surface like an orange peel, with a hills and valleys revealing a rather weak attack of the monomer on the polymer. The palatal surface of the SR-Ivocap resin shows pleats and perpendicular fractures. The surface of the buccal aspect of the ridge is relatively smooth. The Lucitone resin shows a surface with very few irregularities, in which the polymer pellets are well dissolved. In conclusion, no porosities are found on the surface of the various resins. We think that the chemical composition of the resin influences this surface texture and the flasking technique being able to disturb the surface of the resin. PMID- 1933559 TI - [Single tooth loss and osseointegrated implants. Replacement of a maxillary incisor]. AB - The loss of a maxillary incisor is traditionally treated with a three-unit bridge. The progress made in dental implantology since the demonstration of osseointegration by Branemark and al. allows the overall replacement of the missing tooth. Furthermore, the use of osseointegrated implants makes the replacement of a single maxillary incisor reliable and aesthetic, even in cases of moderate gingival and bone recession. In respect of the rules set forth by Branemark and al., it is essential to make a wax-up and a surgical stents. For anterior teeth, the single tooth abutment marketed by Nobelpharma allows the aesthetic margins of the prosthesis to be placed in a sub-gingival position. Once this component is positioned on the fixture, the achievement of the prosthesis is practically identical to traditional metal ceramic crown. The abutment is maintained on the fixture by a screw which can be easily removed and avoids an excess of subgingival cement. Nonetheless, its diameter means that it is reserved for relatively wide teeth. This type of treatment involves the development of a reliable and proven surgical planning for bone grafts, especially in cases of facial traumatism. PMID- 1933560 TI - [Preprosthetic orthodontics: technical aspects of mechanotherapy]. AB - This paper describes the rationale as well as some of the therapeutic tools which may be used during simple preprosthetic orthodontic movements. First a typical bracket is examined: the overall design, the base, the slot and the tie-wings. All those components allow mechanical force transmission from the archwire to the tooth in all three orders of movement. In the classic "edgewise" form of treatment, final placement of the teeth is determined by the bends incorporated into the archwire. Conversely, in the more recent "straight-wire" approach, the angulation of the slot relative to the bracket base provides for an optimal positioning of each individual tooth on the dental arch. Mesio-distal angulation of the roots being referred to as "tip" and bucco-lingual angulation as "torque". The bracket also allows bodily bucco-lingual tooth placement relative to the dental arch as a whole (in-out). Prior to a comprehensive treatment, brackets are placed on teeth according to a standard set of criteria. They must be located midway mesio-distally on the buccal aspect in accordance with the true anatomic longitudinal axis of the root. Its occluso-gingival position however can be slightly adjusted according to the individual needs of the case. In more limited situations, where only a few teeth are moved, those rules have to be adapted since the anchorage teeth are kept stable. Examples are presented which illustrate the key features of limited orthodontic movements. Archwires present themselves in various sections and alloys. The most commonly used metals are stainless steels and the more recently introduced nickel-titanium superelastic alloys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933561 TI - The role of scintigraphy in the lameness evaluation. AB - Bone scanning to help diagnose orthopedic disease has been used in human patients for over two decades. The value of this diagnostic tool has been well established in helping to identify a variety of musculoskeletal conditions. It has only recently been used by veterinarians for more accurate characterization of equine musculoskeletal disease. The technique offers the major advantage of increased sensitivity over standard radiographic imaging. The case material illustrated here shows that except for consistent identification of bone cysts, most of the pathologic changes to the horse's musculoskeletal system that might cause lameness are detected on bone scans. Many acute bone diseases can be diagnosed by scintigraphy that cannot be discerned by radiographs until the condition has become chronic: Because of their body size, these conditions may not be diagnosed at all in horses. Scintigraphy in horses offers the other major advantage of affording accurate imaging of the upper limbs, pelvis, and vertebral column without general anesthesia. Therefore, it has a final advantage of increased safety over conventional radiography because it eliminates the need to perform general anesthesia to study these areas. In the author's experience, if abnormal uptake of isotope in the upper limbs, pelvis or spine is not observed, general anesthesia to radiograph those areas is not warranted. A second major benefit of scintigraphic imaging is to differentiate mixed lameness conditions in which the component of bone disease must be separated from that of soft tissues to arrive at a rational course of treatment or prognosis. Finally, for athletic horses suspected of having lameness due to localized myositis, scintigraphy not only allows confirmation of muscle inflammation but also identifies the muscle bellies injured reasonably accurately so that specific local treatment may be given. Nuclear imaging of equine skeletal disease is an option that should be employed more frequently by equine practitioners for diagnosis of difficult lameness cases. The technique is safe and comparatively inexpensive when one considers the total expense of multiple examinations or radiographic surveys of patients without conclusively diagnosing the source or sources of skeletal pain. This is particularly true when a horse owner becomes dissatisfied and enlists the services of one or more other veterinarians. The equine specialist will maintain better client rapport if he or she suggests referral of the horse to a veterinary medical teaching center or private clinic where scintigraphic imaging can be done rather than having the client become frustrated and seek another opinion elsewhere.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1933562 TI - Equine practice. Advanced diagnostic methods. PMID- 1933563 TI - Contrast radiography of equine joints, tendon sheaths, and draining tracts. AB - Arthrography, tenography, and fistulography (or sinography) can provide additional information about the soft-tissue components of joints, tendon sheaths, and draining tracts, respectively. Arthrography is a valuable aid in the diagnosis of synovial masses, such as villonodular synovitis, and osteochondrosis. Tenography is particularly useful in evaluating chronic tendon sheath distention. Fistulography is an effective means of identifying acute traumatic damage to synovial structures and determining the cause and extent of draining tracts. PMID- 1933564 TI - Treadmill exercise testing. Treadmill installation and training protocols used for clinical evaluations of equine athletes. AB - The use of motorized treadmills has made it possible to evaluate equine poor performance with sophisticated diagnostic techniques during peak exercise. Treadmill exercise tests currently being used for clinical evaluations include treadmill gait analysis, dynamic hoof balancing, endoscopic evaluation of upper airway function, and exercise performance profiling. Large motorized treadmills (1 to 1.5 m in width and 4 to 5 m in length) are best suited for clinical evaluations. Ideally, the treadmill should be installed in-ground using a pit. This type of installation results in the tread surface being at the same level as the surrounding floor. A standard protocol should always be used to train horses to exercise on a treadmill. Training should be designed to introduce the horse to procedures required for a specific clinical evaluation gradually. PMID- 1933565 TI - The use of high-speed treadmills for lameness and hoof balance evaluations in the horse. AB - Examination for lameness remains the most important component of the clinical evaluation for poor performance. Although conventional examinations can be used to diagnose many causes of lameness, treadmill video gait analysis and dynamic hoof balance evaluations have proved to be useful not only for evaluating lameness but also for maintenance of long-term soundness. Treadmill lameness evaluations offer a major advantage compared to conventional evaluations because of the stationary position of the exercising horse relative to the people performing the examination. Lameness is suspected if asymmetric motion is observed or asymmetric sounds of the feet contacting the tread surface are heard during the treadmill evaluation. Localization of lameness to the front or hind legs is the first step in the treadmill gait analysis protocol. In trotting and pacing horses, asymmetric movements associated with foreleg lameness generally are confined to the front end. In contrast to the pacing gait, asymmetric movements associated with hindlimb lameness can involve both the front and rear of the horse at the trot. The evaluation is continued to determine which side of the horse is abnormal. Viewed from the front, horses with primary forelimb lameness appear to have an asymmetric downward rotation of the torso, head, and neck away from the stiffer lame front leg toward the flexed normal leg as it contacts the tread surface. The lame hind leg can appear to be stiff relative to the opposite normal leg. This results in uneven side-to-side oscillations of the pelvis rotating away from the abnormal stiff-appearing hind leg toward the normal, flexed hind leg as it contacts the tread surface. Both front- and hind leg lamenesses cause dissociation of the normal foot-fall sequence, resulting in the alteration of the normal two beat gait at the trot or the pace to a three beat gait. The final step of the lameness examination involves the use of diagnostic regional anesthesia to determine the anatomic location of the lameness. Treadmill video gait analysis can be used to evaluate differences in the horse's gait before and after each anesthetic block. Optimal foot balance during exercise is critical for long-term maintenance of musculoskeletal soundness. Combining slow-motion video gait analysis with treadmill exercise provides an excellent method for evaluating hoof balance at a variety of speeds. Optimal hoof balance can be achieved by using the technique of successive trimming and re-evaluation. The principles of hoof balancing include establishing dorsopalmar or dorsoplantar hoof balance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1933566 TI - Thermography as an aid to the clinical lameness evaluation. AB - Thermography has been shown to be a practical aid in the clinical evaluation of lameness. This modality specifically increases the accuracy of diagnosis. Thermography represents skin temperature, usually pictorially. The techniques involve contacting and noncontacting modalities. Noncontacting thermography, which detects infrared radiation, is the most accurate. In order to be accurate, thermography must be performed in a temperature-controlled, draft-free area. The area should be protected from sunlight to avoid erroneous heating of the skin, and the hair length should be uniform. Thermography detects heat before it is perceptible during routine physical examination; therefore, it is useful for early detection of laminitis, stress fractures, and tendinitis. It offers a noninvasive means of evaluating the blood supply to an injured part and offers one of the only reliable means to evaluate blood flow to the foot of horses with navicular syndrome. Thermography also is useful for the early identification of stress injuries to the contralateral limb of convalescing orthopedic patients. Thermography is an excellent adjunct to clinical and radiographic examination. It is complementary to other imaging techniques such as ultrasonography and scintigraphy. PMID- 1933567 TI - The integration of radiography and alternative imaging methods in the diagnosis of equine orthopedic disease. AB - There is increasing demand on equine practitioners to provide confirmation of their diagnoses. For obscure lameness and for many of the more difficult locomotory problems presented in referral hospitals, the question to be answered is not only how to make the most accurate diagnosis but also how to document the findings so that there is less doubt in the mind of the client. This article describes a quasi algorithmic approach to choosing the best combinations of the increasingly sophisticated imaging methods available for evaluation of orthopedic disease. PMID- 1933568 TI - Advances in motion analysis. AB - Time magnification in motion photography allows the observation of events in the stride cycle that normally are beyond the resolution of the human eye. Quantitative analysis goes a stage further by measuring the stride in terms of timing, distance, and angular variables. Motion analysis is a good technique for detecting left-right asymmetries of gait, and the nature of the asymmetries has some value in locating the site of a lameness. Repeated analyses of the same horse allow an objective assessment of the effects of local anesthesia, surgical treatment, or medication. It is anticipated that this will be one of the most useful clinical applications of motion analysis in the clinical setting. This article reviews the hardware and software available for cinematographic and videographic gait analysis. Manual digitization is tedious and time consuming, but these drawbacks are partially overcome by semi-automated systems, which use point prediction to estimate the location of the markers. Fully automated systems rely on the use of contrasting markers attached to the horse's skin overlying the anatomic landmarks. In some joints, skin motion relative to the underlying bones is sufficient to introduce significant errors in joint angle calculations unless appropriate correction algorithms are applied. PMID- 1933569 TI - Application of clinical exercise testing for identification of respiratory fitness and disease in the equine athlete. AB - Maximal exercise testing is a valuable diagnostic tool for the evaluation of exercise intolerance and level of fitness in the equine athlete. A description of the standardized incremental exercise testing protocol and interpretation of the results of the test is followed by a discussion of more specific diagnostic techniques aimed at identifying pulmonary dysfunction as a cause of suboptimal performance. PMID- 1933570 TI - Dynamic evaluation of the equine upper respiratory tract. AB - Each case of suboptimal equine athletic performance should be evaluated in a comprehensive manner, including physical examination; clinical pathologic analysis; and evaluation of the neurologic system, the musculoskeletal system, and the upper and lower respiratory system. A vital part of this examination is the clinical evaluation of dynamic upper respiratory tract function of the horse during treadmill exercise, which allows the observation of upper respiratory tract function during conditions simulating competitive racing. It generally is agreed that the endoscopic identification of an upper respiratory tract abnormality in the resting horse does not necessarily indicate a clinical problem. It is equally certain that the absence of an upper respiratory abnormality at rest does not rule out the presence of an intermittent obstruction during strenuous exercise. Although many upper respiratory abnormalities may be diagnosed at rest (specifically, most cases of continual epiglottic entrapment and total laryngeal paralysis) the diagnosis of intermittent DDSP, intermittent EE, and some cases of idiopathic laryngeal neuropathy necessitates the observation of the upper respiratory tract during strenuous exercise. This diagnostic technique allows absolute documentation of whether upper airway dysfunction is a contributing factor to inadequate athletic performance in each individual horse. In the decade to come, it is clear that the evaluation of potential upper respiratory tract dysfunction as a cause of exercise intolerance should be performed before specific recommendations are made for treatment in each equine athlete. In many cases, this evaluation has circumvented the unnecessary attempt at correction of suspected but nonexistent respiratory dysfunction. Thus, these horses benefit from a continuation of a comprehensive performance evaluation, enabling an elucidation of the true cause of inadequate performance. The routine use of this diagnostic technique at Tufts University School of Veterinary Medicine's Equine Sports Medicine Center has greatly expanded the documentation of the diversity of upper respiratory dysfunctions that can occur. It also has enabled a precise description of the anatomic abnormalities resulting in each case of upper airway obstruction. In addition, this new knowledge has made us cautious regarding conventional treatment regimens and allowed the capability to individualize attempts at surgical and managemental correction of each dysfunction to optimize the success of the treatment for each horse. PMID- 1933571 TI - Nuclear imaging techniques for equine respiratory disease. AB - When performed on selected clinical cases, ventilation/perfusion scintigraphy provides valuable additional information on regional lung function that is not obtainable from conventional thoracic radiographs. This is particularly true of horses with EIPH, COPD, and those suspected of having some form of small-airway disease. For horses with EIPH, the presence of a perfusion deficit on the scan is considered a key prognostic sign, because it is likely in these cases that irreversible bronchial arterial takeover has occurred in the affected areas of lung. Findings from horses with COPD have improved our understanding of the radiographic patterns of airtrapping and vascular distribution and provided us with a sensitive means of detecting residual bronchial changes in the absence of clinical signs of the disease. Several other scintigraphic parameters such as mucociliary clearance and abscess-avid labeling show promise for future lung imaging on clinical cases but still require further research to develop appropriate techniques for delivery and image analysis. PMID- 1933572 TI - Advances in echocardiography. AB - Before the development of echocardiography, cardiac disease in the horse was diagnosed if a loud heart murmur (grade III-IV/VI or louder) and clinical signs of congestive heart failure (coughing, edema, venous distention, jugular pulsations) were detected on physical examination. Arrhythmias that persisted during and after exercise also indicated cardiac disease, which could be characterized electrocardiographically. Electrocardiography, thoracic radiography, angiography, cardiac catheterization, and oximetry could add only small pieces of information about the heart. M-mode echocardiography provided the first "window" with which to evaluate the heart and its intracardiac structures, albeit an ice-pick one-dimensional view. With M-mode echocardiography, the diameter of the aorta at the valves, the left ventricle, right ventricle, and left atrial appendage, as well as the thickness of the interventricular septum and left ventricular free wall, could be measured. Motion and thickness of the tricuspid, mitral, and aortic valves could be assessed, but only in a one dimensional plane. Two-dimensional echocardiography provided an added dimension, resulting in visualization of all the intracardiac structures, aorta, and pulmonary artery. Two-dimensional echocardiography became the diagnostic technique of choice for the evaluation and characterization of congenital cardiac disease in critically ill neonates, as well as in adult horses. Two-dimensional echocardiography also improved the ability to diagnose valvular regurgitations, characterize valvular lesions (bacterial endocarditis, ruptured chorda tendineae), myocardial function (segmental wall motion abnormalities), atrial size, mass lesions (endocarditis, neoplasia, and thrombi), and pericardial effusion. Information about blood flow was obtained using contrast echocardiography but was limited to certain cardiac abnormalities (congenital cardiac defects and tricuspid regurgitation). This information about blood flow was limited to the detection of positive or negative contrast jets. Comprehensive information about blood flow was lacking until the application of Doppler echocardiography to equine cardiology. Pulsed-wave and color flow Doppler echocardiography resulted in precise localization of the abnormal blood flow and semiquantitation of the shunt flow or regurgitant jet. Color flow Doppler echocardiography sped up the localization and semiquantitation of the jet in many instances and provided some information about blood flow velocity in the enhanced and variance modes. The peak velocity of jets can be determined using continuous wave Doppler echocardiography. This value then can be used to estimate pressure difference between cardiac chambers or to calculate cardiac output noninvasively if angles parallel to flow can be obtained. Thus, information about cardiac size, function, and blood flow can be combined to diagnose cardiac disease in horses and to formulate a prognosis for life and performance. PMID- 1933573 TI - Advances in diagnostic ultrasonography. AB - A wide variety of ultrasonographic equipment currently is available for use in equine practice, but no one machine is optimal for every type of imaging. Image quality is the most important factor in equipment selection once the needs of the practitioner are ascertained. The transducer frequencies available, transducer footprints, depth of field displayed, frame rate, gray scale, simultaneous electrocardiography, Doppler, and functions to modify the image are all important considerations. The ability to make measurements off of videocassette recorder playback and future upgradability should be evaluated. Linear array and sector technology are the backbone of equine ultrasonography today. Linear array technology is most useful for a high-volume broodmare practice, whereas sector technology is ideal for a more general equine practice. The curved or convex linear scanner has more applications than the standard linear array and is equipped with the linear array rectal probe, which provides the equine practitioner with a more versatile unit for equine ultrasonographic evaluations. The annular array and phased array systems have improved image quality, but each has its own limitations. The new sector scanners still provide the most versatile affordable equipment for equine general practice. PMID- 1933574 TI - Future diagnostic methods. A brief look at new technologies and their potential application to equine diagnosis. AB - We live in an age in which highly sophisticated computerized equipment and imaging methods are becoming increasingly available. Demand from clients requires that we as veterinary professionals keep our eyes on the future potential of these technologies for diagnosis and treatment. This article briefly reviews some of the techniques that are just around the corner for the progressive equine practitioner. PMID- 1933575 TI - National Nurses Day: launch your own PR campaign. PMID- 1933577 TI - ANA and CNA to conduct child immunization program. PMID- 1933576 TI - Indigent health care decisions now in local hands. PMID- 1933578 TI - Diabetic bone disease. PMID- 1933579 TI - Fracture rates as a function of forearm mineral density in normal postmenopausal women: retrospective and prospective data. AB - Fracture histories were obtained from 492 normal postmenopausal women in 1983 and again in 1988, and related to forearm mineral content and density determined in 1983. All peripheral fractures, except those attributable to road traffic accidents, were included. There was only one hip fracture in the series. The total number of postmenopausal fractures was 183 in 149 subjects. In both the retrospective and prospective studies, fracture rates were inversely related to bone status and more significantly to bone density than to bone mass. In the pooled data, the fracture rate was three times as high in women with bone densities more than 4 standard deviations below the young normal mean as in those with bone densities above the mean. On logistic regression, the adjusted relative risk of fracture (odds ratio) in subjects more than 4 standard deviations below the young mean compared with those above the mean was 5.5 (2.7-11.4). PMID- 1933580 TI - Treatment of Paget's disease of bone with a combination of intranasal salmon calcitonin and oral calcium and thiazide. AB - The purpose of this study was to establish the smallest dose of nasally administered salmon calcitonin (SCT) which, if given in conjunction with a previously published calcium/thiazide treatment, would be as effective as parenteral SCT in the treatment of Paget's disease of bone. Forty patients suffering from symptomatic Paget's disease were treated with 0.5 g calcium three times daily, 10 mg/day clopamide, and 400 IU nasally administered salmon calcitonin given once or twice weekly. This regimen was given for 5 months, after which all treatment was ceased for 4 months. Parenteral SCT (100 IU) was then given three times weekly for 5 months to 25 of the patients. With the oral/nasal treatment, the plasma alkaline phosphatase level (AP) decreased by 30 +/- 15 (SD)% when the SCT was given once weekly and by 39 +/- 11% (P less than 0.05) when the SCT was given twice weekly. There were similar decreases in the fasting urinary hydroxyproline:creatinine ratios. The parenteral SCT reduced the AP by 33 +/- 23%. Though reduction in bone pain was similar with both treatments, most patients preferred the oral/nasal treatment. It is concluded that the oral/nasal treatment, when the SCT is given twice weekly, has similar efficacy to parenteral SCT, and is a well tolerated, effective initial treatment for Paget's disease of bone. PMID- 1933582 TI - Precision and stability of dual-energy X-ray absorptiometry measurements. AB - This study was performed to determine the precision and stability of dual-energy X-ray absorptiometry (DEXA) measurements, to compare bone mineral density (BMD) of subjects measured by DEXA and radionuclide dual-photon absorptiometry (DPA), and to evaluate different absorber materials for use with an external standard. Short-term precision (% coefficient of variation, CV) was determined in 6 subjects scanned six times each with repositioning, initially and 9 months later. Mean CV was 1.04% for spine and 2.13% for femoral neck BMD; for whole-body measurements in 5 subjects, mean CV was 0.64% for BMD, 2.2% for fat, and 1.05% for lean body mass. Precision of aluminum phantom measurements made over a 9 month period was 0.89% with the phantom in 15.2 cm, 0.88% in 20.3 cm, and 1.42% in 27.9 cm of water. In 51 subjects, BMD by DEXA and DPA was correlated for the spine (r = 0.98, P = 0.000) and femoral neck (r = 0.91, P = 0.000). Spine BMD was 4.5% lower and femoral neck BMD 3.1% higher by DEXA than by DPA. An aluminum phantom was scanned repeatedly, in both water and in an oil/water (30:70) mixture at thickness ranging from 15.2 through 27.9 cm. Phantom BMD was lower at 15.2 cm than at higher thicknesses of both water and oil/water (P = 0.05, ANOVA). The phantom was scanned repeatedly in 15.2, 20.3, and 27.9 cm of water over a 9 month period. In 15.2 and 20.3 cm of water, phantom BMD did not vary significantly whereas in 27.9 cm of water (equivalent to a human over 30 cm thick), phantom BMD increased 2.3% (P = 0.01) over the 9 months. PMID- 1933581 TI - Short-term course of 1,25(OH)2D3 stimulates osteoblasts but not osteoclasts in osteoporosis and osteoarthritis. AB - We investigated the effect of short-term, 1,25-dihydroxyvitamin D3 therapy (4 micrograms/day for 4 days) on calcium metabolism in 27 postmenopausal women (11 cases with osteoporosis and 16 cases with osteoarthritis). Bone mass at the axial and appendicular skeleton was higher in osteoarthritis than in osteoporosis. Initial values of calcium metabolism were similar. Osteoporotic and osteoarthritic patients responded with a similar significant increase in serum osteocalcin (+61% and +54%, respectively), fasting urinary calcium excretion (+178% and +124%, respectively) and 24 hour calcium excretion (+148% and +142%, respectively). Parathyroid hormone (PTH) levels decreased significantly in both groups (-30% and -18%, respectively). Osteoclastic bone resorption, evaluated by urinary hydroxyproline excretion, was not stimulated in either group. We conclude that in osteoporosis and also in osteoarthritis (1) 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) stimulation of osteoblast function is similar in production of osteocalcin; (2) the vitamin D target tissues react adequately to 1,25(OH)2D3 stimulation; (3) short-term high dose of 1,25(OH)2D3 does not stimulate bone resorption; and (4) the differences in bone mass between osteoarthritis and osteoporosis are not related to an alteration of the responsiveness to stimulation by 1,25 (OH)2D3. PMID- 1933583 TI - Infusion of zinc inhibits serum calcitonin levels in patients with various zinc status. AB - Serum concentrations of ionized calcium, parathyroid hormone, and calcitonin were measured during zinc infusion in patients of short stature (n = 15); those with insulin-dependent diabetes mellitus (n = 13); and age-matched controls (n = 10). The increase in serum zinc concentrations after zinc infusion resulted in a decrease in the serum calcitonin concentrations but not in concentrations of ionized calcium and parathyroid hormone. A significant negative correlation was obtained between body zinc clearances and decreases in serum calcitonin levels at 60 minutes after the infusion of zinc. Thus, we found a relationship between infusion of zinc and the regulation of calcitonin secretion. We propose that an increase in the serum zinc pool plays a definite role in inhibiting calcitonin secretion from thyroid tissue. PMID- 1933584 TI - Androgen receptors in osteoblast-like cell lines. AB - Although androgens exert major effects on bone remodeling, the mechanisms by which they exert their effects remain unclear. Recently, it has become apparent that receptors for sex steroids may be present in osteoblastic cells. We have examined several cell lines with osteoblastic phenotypes to determine if specific, high affinity androgen receptors are present. Two cell lines of human origin (Saos-2 and U2-OS) and one of rat origin (UMR-106.01) were studied. Androgen binding sites were present in all cell lines. Binding affinities were high (KD = 1.6 - 2.5 x 10(-10) M), and similar to those in classical androgen target tissues (prostate, kidney). Concentrations were greater in the human cell lines (1277 and 1605 sites/cell) than in the rodent line (74 sites/cell). In the human cell lines androgen binding was also specific and typical of androgen receptors in other tissues. Specific estrogen binding was not present in the UMR 106.01 cells, and no estrogen receptors were detectable in the human cell lines using an enzyme-linked receptor immunoassay. Specific binding for progesterone was also absent in the UMR-106.01 cells, but progesterone receptors were detected immunologically in the Saos-2 (119 sites/cell) and U2-OS (118 sites/cell) lines. These findings indicate the presence of androgen receptors that are of similar character to those in classical androgen target tissues, and suggest that the study of these cell lines may be useful in the study of the regulation of androgen effects in osteoblasts. PMID- 1933585 TI - Distribution of type X collagen in tibiotarsi of broiler chickens with vitamin D deficiency. AB - Type X collagen is a significant component of the extracellular matrix of the hypertrophic zone of physeal cartilage, but its precise role in endochondral ossification has not been determined. The concentration of type X collagen increases in physeal cartilage in chicks with vitamin D deficiency. The purpose of our study was to determine whether defective endochondral ossification due to vitamin D deficiency was associated with abnormalities in the distribution of type X collagen in the proximal tibiotarsus of chicks. To accomplish this, we induced vitamin D deficiency in broiler chicks and sequentially evaluated the pattern of type X collagen immunoreactivity in the proximal tibiotarsus using a monoclonal antibody specific for chicken type X collagen. Type X collagen immunoreactivity was present in the matrix of the prehypertrophic zone, hypertrophic zone, cartilage cores of the primary spongiosa, and within the chondrocytes of the prehypertrophic and early hypertrophic zones in vitamin D deficient and D-replete chicks. However, rachitic chicks exhibited two consistent differences in type X collagen immunoreactivity: hypertrophic chondrocytes in the late hypertrophic zone and primary spongiosa contained intracellular type X collagen; and type X collagen was concentrated into laminated aggregates in the pericellular and territorial matrices in the late hypertrophic zone and primary spongiosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933588 TI - Calcitonin and bone mass status in congenital hypothyroidism. PMID- 1933586 TI - Heterotopic ossification: clinical and cellular aspects. PMID- 1933587 TI - Long-term pulsed electromagnetic field (PEMF) results in congenital pseudarthrosis. AB - Ninety-one patients with congenital pseudarthrosis of the tibia have been treated with pulsed electromagnetic fields (PEMFs) since 1973 and all except 4 followed to puberty. Lesions were stratified by roentgenographic appearance. Type I and type II had gaps less than 5 mm in width. Type III were atrophic, spindled, and had gaps in excess of 5 mm. Overall success in type I and II lesions was 43 of 60 (72%). Of those 28 patients seen before operative repair had been attempted, 7 of 8 type I lesions healed (88%), whereas 16 of 20 type II lesions healed (80%) on PEMFs and immobilization alone. Only 19% (6 of 31) type III lesions united, only one of which did not require surgery. Sixteen of 91 limbs (18%) were ultimately amputed, most before treatment principles were fully defined in 1980. Fourteen of these 16 patients (88%) had type III lesions. Refracture occurred in 22 patients, most as the result of significant trauma, in the absence of external brace support. Twelve of the 19 refractures, retreated with PEMFs and casts, healed on this regime. Episodic use of PEMFs proved effective in controlling stress fractures in several patients until they reached puberty. PEMFs, which are associated with no known risk, appear to be an effective, conservative adjunct in the management of this therapeutically challenging, congenital lesions. PMID- 1933589 TI - Pathogenesis of osteoporosis. AB - The final clinical outcome of the osteoporotic process is a fracture, which can occur as a result of minimal trauma or even spontaneously. At present low bone mass is regarded as the main contributor to bone fragility, but possible qualitative changes in the bone matrix must also be considered. Two factors which determine the level of bone mass at any age are the obtained peak bone mass and duration and rate of bone loss. Peak bone mass is achieved during the first three decades of life. Genetic and nutritional factors as well as mechanical stress on the skeleton obviously play crucial roles in determining peak bone mass. Two phases of bone loss--age-related and menopause-related--dictate the final bone mass at old age. Postmenopausal osteoporosis is a particular example of unbalanced bone resorption leading to net bone loss. An increasing number of systemic and local factors have been found to participate in the regulation of bone remodeling. PMID- 1933590 TI - Epidemiologic studies of osteoporotic fractures: methodologic issues. AB - Cross-sectional and case-control studies are efficient and inexpensive approaches to the study of osteoporosis; their validity depends primarily on how the subjects are sampled. Retrospective studies of fractures may be biased if measurements change as a result of the fracture. Prospective cohort studies are less prone to such biases but are expensive. Randomized blinded trials are ideal for assessing studying single factors but trials are sometimes flawed by avoidable problems. Patient reports about risk factors are imperfect but sufficiently accurate to detect most strong associations between risk factors and osteoporosis. Noise in the measurement of risk factors will cause studies to underestimate the effect of these factors. About one-sixth of recalls of falls and fractures are incorrect. Self-report of vertebral fractures is unreliable and biased and there is controversy about how to define vertebral fractures on lateral X-ray film. Clinical and epidemiological research in osteoporosis would be advanced by greater care in the design of studies and methods of measurement. PMID- 1933591 TI - Bone density measurements. AB - Early diagnosis of osteoporosis is difficult. Bone density measurements, however, are helpful in screening patients at risk. Technology now provides means of measuring densities of both peripheral and central bones. The most practical method is dual X-ray densitometry, which is of good sensitivity and accuracy. Single photon absorptiometry on peripheral bones can be used to screen populations at risk. Computed tomography is also useful but the radiation dose is relatively high. In dual X-ray densitometry, calibration methods and comparisons with reference values are fairly reliable. The best sites for measurements are the lumbar spine and proximal femur, in which osteoporotic fractures are common. In general, however, one measurement is not enough. Biological variation is great. Repeated measurements will allow estimation of the rate of bone loss. Precise location of a previous site is sometimes difficult on reexamination and extraskeletal calcifications can be sources of error. Bone densitometry in connection with the prevention and treatment of osteoporosis is fairly easily performed with a single patient. Knowledge about the correlation between bone density and fracture risk is not yet adequate. The results of measurement of bone mineral density relate only to mineral content, not bone quality, i.e., differential diagnosis of osteoporosis and osteomalacia is not possible. PMID- 1933592 TI - Use of a marker of collagen formation in osteoporosis studies. AB - Type I collagen accounts for most of the organic matrix of bones, but it is also an important constituent of soft connective tissue. Assessment of the turnover of such collagen is particularly relevant to bone metabolism. Determination of the carboxyterminal propeptide of type I procollagen (PICP) is a means of estimating the rate of type I collagen synthesis in the body. Serum concentrations of PICP have been shown to correlate with the rate of bone formation. PMID- 1933594 TI - Use of histological methods in studies of osteoporosis. AB - The diagnosis of osteoporosis is usually based on using noninvasive methods. However, often bone histomorphometry is needed for the exclusion of other metabolic bone diseases and the evaluation of cellular mechanisms of osteoporosis. A combination of determination of serum biochemical parameters, measurement of bone mineral density, and quantitative dynamic evaluation of bone histology is an ideal tool for the evaluation of a patient with osteoporosis. PMID- 1933593 TI - Use of non-collagen markers in osteoporosis studies. AB - Clinical and research laboratories routinely measure various hormonal and nonhormonal parameters of calcium and phosphorus metabolism, and markers of bone turnover. Such measurements may help clinical decision-making relating to metabolic bone disease and osteoporosis. Molecular biological and cell-culture techniques are being used in basic biochemical research on bone-cell metabolism. Results may aid understanding of normal and abnormal regulation of the bone-cell metabolism, and thus provide further insights relating to the diagnosis and prevention of osteoporosis. PMID- 1933595 TI - Calcium requirements for optimal skeletal health in women. AB - There is a great deal of uncertainty concerning the requirements of calcium for skeletal health. Some argue that all mixed diets contain sufficient calcium whereas others suggest that most of the world's population is calcium deficient. This paper reviews the sources of these conflicting views and the assumptions on which both are based. PMID- 1933596 TI - Lifelong calcium intake and prevention of bone fragility in the aged. AB - Primary prevention of osteoporosis involves achieving the full genetic potential for bone mass. Secondary prevention is concerned with protecting what bone mass a woman may have at her current age. Calcium plays an important role in both. Calcium requirement varies with stage of growth, with physiological drains (e.g., pregnancy and lactation), and with factors that influence absorption and excretory loss (e.g., gonadal hormone status and sodium and protein intakes). The evidence is strong that prevailing calcium intakes contribute to the low bone mass component of osteoporotic fragility and that increases in intake would reduce the osteoporotic fracture burden. At the same time it needs to be emphasized that bone health is a multifactorial affair and that meeting calcium requirements alone will neither guarantee optimal bone growth nor protect against bone loss if other critical factors are missing. For example, calcium affords only minimal protection against either immobilization or estrogen withdrawal bone loss. Thus, while assuring an adequate calcium intake remains a sound strategy, it cannot be considered a total preventive for osteoporosis. PMID- 1933597 TI - Is there a role for vitamin D in osteoporosis? AB - Vitamin D has certain clearly defined effects on bone: vitamin D deficiency results in defective bone mineralization, whereas 1,25-dihydroxy-vitamin D3 (1,25 (OH)2D3) stimulates bone resorption. Studies of the use of 1,25-(OH)2D3 to prevent or treat osteoporosis have given conflicting results concerning bone remodeling. However, 1,25-(OH)2D3 or other vitamin D metabolites seem to play a role in the correction of calcium malabsorption, which is a common feature in osteoporosis. PMID- 1933598 TI - Significance of osteoporosis: a growing international health care problem. AB - The international incidences of osteoporosis and the hip fracture syndrome are increasing at alarming rates. The estimated increases in rates of fracture over the next decade may also prove to be conservative, because of progressive increases in numbers of elderly people who will fall because of muscular degeneration, failing vision, postural hypotension, and loss of cognitive function resulting from the ever-increasing abuse of mixtures of drugs. Changing patterns of hip fracture care, including extended use of hospital beds and of rehabilitation and nursing-home beds could lead to substantial and escalating annual costs in national health care budgets. Such a budget currently approximates 10 billion dollars in the United States alone. PMID- 1933599 TI - Physical activity effects on bone metabolism. AB - The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows. PMID- 1933601 TI - Long-term treatment of established osteoporosis with intranasal calcitonin. AB - We examined the long-term effects of intranasal administration of salmon calcitonin on bone and calcium metabolism in women with established osteoporosis (forearm fracture). Over a period of 5 years, 14 women received discontinuous calcitonin (200 IU) plus calcium (500 mg) daily for 3 years or 4 years. To allow assessment of the optimum duration of therapy, patients in whom treatment had been for shorter intervals were also included. At the end of the first 2 years, a group receiving placebo had lost significantly more bone from their spines and forearms than the group receiving calcitonin in the first year (P less than 0.01). In the 14 women who completed a further 3 years on calcitonin, the bone mineral contents of the spines increased continually. Bone loss in the forearm was arrested for 1 year. Treatment lasting for about 2 years prevented bone loss in both areas. Treatment for 3 years resulted in net gains in spinal bone but no further benefits in relation to forearms. Biochemical parameters of bone turnover (serum alkaline phosphatase levels, plasma bone Gla protein levels, and fasting urinary hydroxyproline/creatinine levels) exhibited similar declines irrespective of the duration of treatment. It is concluded that long-term intranasal treatment with calcitonin produced net gains in spinal bone and that optimum response in forearms was achieved using discontinuous therapy. The ratio between periods with and without treatment was between 1:2 and 2:3. PMID- 1933600 TI - Role of oestrogen in the development of osteoporosis. AB - The evidence now strongly supports a central role for oestrogen in the maintenance of the normal female skeleton. Loss of endogenous oestrogen leads to a period of accelerated bone loss which can be prevented with appropriate oestrogen replacement. The route of administration is not important provided adequate dosages are prescribed. Oestrogens may exert their actions by a direct steroid receptor mechanism or via local and/or systemic factors such as cytokines, prostaglandins or calcitonin. As the requirement for osteoporosis prevention grows, it is essential that the extent of the involvement oestrogen has in skeletal homeostasis is fully recognized. PMID- 1933602 TI - Fluoride therapy for osteoporosis: a review of dose response, duration of treatment, and skeletal sites of action. AB - Osteoporosis is a disease characterized by a reduction in bone density which predisposes to fracture after even minimal trauma. Fluoride, because it has consistently been shown to stimulate bone formation and increase trabecular bone density, has been widely studied for the treatment of osteoporosis. The article focuses on the dose response, duration of treatment, and skeletal sites of action of fluoride; we also include comments on the effect of fluoride on vertebral and appendicular fracture rates. The skeletal response to fluoride doses, ranging from 15 to 43 mg elemental fluoride per day, included a linear increase in spinal bone density at an average rate of 1.25 +/- 0.91 mg/cm3 per month. The rate of increase in spinal bone density was related to the dose of fluoride (r = 0.34, P less than 0.03). Spinal bone density had increased above the fracture threshold in 44% of patients treated with fluoride for 32 +/- 10 months. The time required to achieve this goal was, however, influenced by the pretreatment spinal bone density and interpatient variation in response to fluoride treatment. Patients whose spinal bone density remained below the fracture threshold had lower pretreatment bone densities and/or slower rates of increase in spinal bone density (P less than 0.001). The osteogenic effect of fluoride was not limited to the spine. After 2 years of fluoride therapy, we found bone density in the femoral condyle (measured by QCT) to have increased by 13 +/- 2.6 mg/cm3 (n = 38, P less than 0.001); bone density in the hip (measured by DPA) was increased by 0.0261 +/- 0.015 g/cm2 (n = 55, P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933603 TI - Is fluoride treatment justified today? AB - Fluoride has been used for the treatment of osteoporosis since 1961, because it increases trabecular bone mass in the spine and may be effective in the treatment of spinal osteoporosis. Fluoride treatment is still controversial because of its side effects, the high rate of non-responders, possible osteomalacic effect on bone, deleterious effects on cortical bone, and especially because of its uncertain effect on fracture rate. At present, fluoride therapy is highly questionable in the prophylaxis and treatment of osteoporosis. PMID- 1933605 TI - Osteoporosis risk factors in perimenopausal women. PMID- 1933604 TI - Alcohol and bone. AB - Abuse of alcohol is considered to be an important risk factor for fractures and osteoporosis. Alcohol abuse is associated with deleterious changes in bone structure detected by histomorphometry, and with a decrease in bone mineral density. These changes may also be produced by factors commonly associated with alcohol abuse, e.g., nutritional deficiencies, liver damage, and hypogonadism. Thus the etiology of alcohol-associated bone disease is multifactorial. Alcohol has, however, clear-cut direct effects on bone and mineral metabolism. Acute alcohol intoxication causes transitory hypoparathyroidism with resultant hypocalcemia and hypercalciuria. Prolonged moderate drinking elevates serum parathyroid hormone (PTH) levels, whereas chronic alcoholics are characterized by low serum levels of vitamin D metabolites with resultant malabsorption of calcium, hypocalcemia, and hypocalciuria. Independently of whether alcohol consumption is of short duration, social, or heavy and chronic, it seems to suppress the function of osteoblasts, as evidenced by low serum levels of osteocalcin. It has recently been reported, however, that alcohol can also have a beneficial effect on bone. Among postmenopausal women, moderate alcohol consumption correlates positively with central and peripheral bone mineral density, and with serum estradiol levels. PMID- 1933606 TI - Factors related to risk of osteoporosis in 50-year-old women. PMID- 1933607 TI - Senile osteoporosis and femoral neck fractures in long-stay institutions. AB - The incidence rates of femoral neck fractures, one of the most serious complications of senile osteoporosis, were 8.7-9.4 times greater in old people in long-stay institutions than among old people living at home. The relative proportion of fracture patients admitted from long-stay institutions was four times greater than expected. Operative intervention of femoral neck fracture patients seemed to be successful: 85.4%-88.5% of patients were discharged to the environments from which they had been admitted. PMID- 1933608 TI - Incidence of femoral neck fractures: senile osteoporosis in Finland in the years 1970-1985. AB - The number of new femoral neck fractures in Finland doubled between 1970 and 1985. This is a result of the progressive increase in the age of the population as well as of an increase in incidence rates. The former factor predominated in women, while the latter was more characteristic among men. The increase in incidence rates seemed to be based on a cohort effect. PMID- 1933609 TI - Effect of exercise on osteoporosis induced by ovariectomy in rats. PMID- 1933610 TI - Effects of long-term running on spinal mineral content in dogs. AB - The effects of long-term running were studied in 20 beagle dogs. Ten dogs ran from the age of 15 weeks to the age of 70 weeks in a progressive program for up to 40 km/day. Ten sister dogs spent the same time in individual cages. At the age of 70 weeks the spines of the dogs were studied with regard to mineral density using dual-energy X-ray absorptiometry and quantitative computed tomography. Mineral density was lower in the running dogs than in the controls. PMID- 1933611 TI - Serum vitamin D level after an annual intramuscular injection of ergocalciferol. AB - An annual intramuscular injection of ergocalciferol (150,000 IU) normalized low serum (25(OH)D concentrations in elderly people for 1 year. The treatment had a slight effect on serum 24,25(OH)2D levels but no effect on 1,25(OH)2D levels. PMID- 1933612 TI - Effects of vitamin D and calcium on markers of bone metabolism in geriatric patients with low serum 25-hydroxyvitamin D levels. PMID- 1933613 TI - Bone remodeling in osteoporosis associated with rheumatoid arthritis. PMID- 1933614 TI - Use of nasally administered salmon calcitonin in preventing bone loss. AB - This article reviews several of our studies in which we evaluated the effect of nasal salmon calcitonin in preventing bone loss in normal women just after menopause. In the first study, after treatment with nasal salmon calcitonin, bone loss stopped and, in fact, actually increased slightly. In contrast, the placebo group continued to lose bone mass. On the other hand, bone mass in the forearm, which has more cortical bone, showed no change in response to nasal salmon calcitonin. The effect of salmon calcitonin nasal spray in women with established osteoporosis has also been studied. In one study, bone mass in the forearm was constant in the group receiving nasal salmon calcitonin plus calcium, whereas bone mass in the placebo plus calcium group decreased by roughly 2%. Similarly, patients in the group without any treatment also lost 2%. The effect of nasal salmon calcitonin is probably the result of a reduction in the bone resorption to a level seen in premenopausal females. When women were divided according to their baseline bone turnover or initial bone mass, the women with the highest turnover level (assessed by alkaline phosphatase or fasting urinary hydroxyproline) or the lowest bone mass were the group with the greatest increase in bone mass. In conclusion, treatment with salmon calcitonin nasal spray in patients with established osteoporosis stops bone loss, normalizes bone turnover, and causes no subjective or objective side effects. PMID- 1933615 TI - Heterogeneity of osteoporotic syndromes and the response to calcitonin therapy. AB - In the past, the osteoporotic syndrome has been variably classified as "senile," "postmenopausal," "involutional," "Type I," and "Type II," primarily on the basis of age, fracture incidence patterns, and/or fracture sites. Histological analyses of bone biopsy specimens from osteoporotic individuals also reveal a wide spectrum of cellular activity and rates of bone formation and resorption. These range from those that show an abundance of osteoblasts and osteoclasts with increments in both bone formation and bone turnover (i.e., "active" or "high turnover" osteoporosis) to others demonstrating minimal cellular activity and relatively little active bone formation or resorption ("inactive" or "low turnover" osteoporosis). The varied states of bone activity are reflected in associated changes in noninvasive biochemical markers of bone turnover such as circulating bone-gla-protein (BGP) or the urinary hydroxyproline/creatinine ratio (OH-Pr/Cr). Both BGP and OH-Pr/Cr are elevated in patients with high-turnover osteoporotic syndromes. The significance of this mode of categorizing osteoporotic patients is exemplified by the response to remedial therapy such as salmon calcitonin. Recent studies demonstrate a striking sensitivity of patients with high-turnover osteoporosis to calcitonin, with as much as 22% increments in vertebral bone mass recorded during a 12-month therapeutic interval. These promising results should also be compared with other forms of therapy in which an increase in vertebral bone mass of only 7-8% was sufficient to cause a significant decrease in the incidence of vertebral fracture rates. PMID- 1933616 TI - Future horizons for calcitonin: a U.S. perspective. AB - Injectable salmon calcitonin has been in use in the United States for more than a decade for the treatment of patients with postmenopausal osteoporosis, Paget's disease, and hypercalcemia. Sandoz Pharmaceuticals Corp. is currently in the process of developing a nasal formulation of salmon calcitonin. Studies are in progress to compare the efficacy of this nasal formulation with that of the injectable hormone in preventing bone loss and restoring bone, as well as in reducing pain associated with bone diseases. The rationale for development of a nasal formulation is to attempt to reduce the incidence of systemic side effects, inconvenience, and resulting noncompliance associated with the injectable product. In studies to date, the nasal form of calcitonin has been well tolerated by most subjects and was not notably associated with nasal irritation. The tolerability seen within the context of clinical trials suggests that a nasal formulation might be well accepted, even among asymptomatic osteoporotic patients. Asymptomatic patients with secondary osteoporosis due to steroid administration or solid organ transplantation may also be studied as possible candidates for the prophylactic use of this drug. Additional future research includes the development of an oral calcitonin agent. PMID- 1933617 TI - Clinical efficacy of salmon calcitonin in Paget's disease of bone. AB - Clinical interest in salmon calcitonin began in 1972 when this peptide was shown to be effective in the treatment of Paget's disease. Salmon calcitonin is more potent than porcine calcitonin, with human calcitonin intermediate in potency. Salmon calcitonin is a highly effective therapeutic agent in the treatment of Paget's disease. During chronic treatment with salmon calcitonin, alkaline phosphatase activity and urinary hydroxyproline excretion decrease on an average of 50% in patients with Paget's disease. Patients may experience a variety of clinical benefits during chronic treatment, including relief of bone pain, a reversal of neurological deficits, stabilization or improvement of hearing loss, and improvement of vascularity of bone. Radiologic healing of osteolytic lesions in particularly striking with calcitonin treatment. Paget's disease patients prefer treatment with salmon calcitonin administered by means of a nasal spray. Salmon calcitonin has an excellent safety profile and produces mild side effects in a small percentage of patients. The most common side effects associated with salmon calcitonin administration are nausea and facial flushing. It is unusual to observe severe side effects. In about 20% of patients, production of antibodies may neutralize the effects of the exogenously administered calcitonin; these patients respond to human calcitonin. At this time salmon calcitonin should still be considered a valuable therapeutic agent in the treatment of Paget's disease, particularly in patients with osteolytic lesions. PMID- 1933618 TI - Use of calcitonin in the treatment of bone pain associated with osteoporosis. AB - In osteoporosis, calcitonin exerts an analgesic effect that is unrelated to its effect on bone. Although the precise mechanism has yet to be clarified, there is some evidence that the analgesic effect of calcitonin may be mediated through the endogenous opioid system. The intranasal administration of calcitonin seems to be more effective in producing analgesia than parenteral administration. PMID- 1933619 TI - Patients in shock: some questions about resource allocation. PMID- 1933620 TI - New perspectives in shock: expanding our horizons. AB - With the introduction of exciting new shock-related research into clinical practice, coupled with the development of advanced physiologic monitoring, we have expanded our horizons considerably. Our approach to shock is moving beyond single-organ support to a more conceptual and global approach. We now stand a chance at making a difference in patient's experiencing shock, rather than just defining separate etiologies. PMID- 1933621 TI - Vasoconstriction to hypoxia of the human internal mammary artery. AB - Experiments were designed to determine the role of the endothelium in response to hypoxia in the human internal mammary artery (IMA). Segments of IMA were harvested during coronary artery bypass surgery. Rings (4 mm in length) of IMA, with and without endothelium, were suspended to force transducers in organ baths containing a physiologic salt solution (37 degrees C, 95% O2/5% CO2, and pH = 7.4). The rings were contracted with norepinephrine (NE, 1 x 10(-7) M, initial tension), and then exposed to hypoxia (95% N2/5% CO2, PO2 = 35 +/- 5 mmHg). In IMA segments with endothelium, hypoxia caused an initial, transient relaxation (hypoxic inhibition) to 52 +/- 9% of the initial tension, followed by contraction of the blood vessel (hypoxic potentiation; 178 +/- 10% of initial tension). In vessels without endothelium, hypoxia only induced relaxation (to 10 +/- 2% of initial tension). In vessels with endothelium, reoxygenation induced transient rapid relaxation (to 31 +/- 12%; post-hypoxic inhibition) which then stabilized to 50 +/- 14% of the initial tension. However, segments without endothelium returned to their initial tension. Indomethacin (1 x 10(-5) M) reduced the endothelium-dependent hypoxic contraction and abolished the hypoxic and post hypoxic inhibition. Free radical scavengers (superoxide dismutase plus catalase and deferoxamine) did not modify the responses to hypoxia and reoxygenation. These experiments indicate that hypoxia induces the release of an endothelium derived constricting cyclooxygenase product from the human IMA endothelium, and that reoxygenation causes release of a cyclooxygenase-dependent endothelium derived relaxing factor. The release of endothelium-derived constricting factor(s) could induce vasospasm and cause cardiovascular collapse if IMA grafts are exposed to hypoxia perioperatively. PMID- 1933622 TI - Aneurysmal subarachnoid hemorrhage. Report of 219 cases in Chang Gung Memorial Hospital. AB - Two hundred and nineteen cases with aneurysmal subarachnoid hemorrhage treated at Chang Gung Memorial Hospital from January 1986 to December 1989 were studied. Their ages ranged from 19 to 76, with a mean of 55 +/- 16 years. About one third of the cases occurred in the age group of 50 to 59 years. Females were predominant with a female to male ratio of 2:1, but there was a male predominance below age 40. The most common site of aneurysm was the anterior communicating artery. Rebleeding, delayed vasospasm with cerebral infarction, and hydrocephalus were the main causes of death or disability. The mean follow-up of 6 months for the whole group showed a 59% favorable outcome, 13% severe disability and a 28% mortality. For those 166 patients who underwent surgical treatment, there was 8% mortality. PMID- 1933623 TI - Mycoplasma pneumoniae pneumonia: clinical analysis of 45 cases. AB - Mycoplasma pneumoniae (M. Pneumoniae) is a primarily pathogen of the respiratory tract. The clinical characteristics, laboratory findings, and roentgenographic patterns of 45 patients with serologically proven M. pneumoniae pneumonia admitted to Chang Gung Hospital from 1981 to 1989 have been reviewed. There were 23 males and 22 females. Forty-one (91%) were below 40 years old and 13 patients (29%) were below 5 years old. Fever, cough and chest rales were the most common symptoms and signs. A transient mild elevation of liver enzymes was seen in 33% of the patients, most of whom were below the age of ten (73%). A leukocyte count over 15,000/cu mm was not rare (16%). Roentgenographic features included unilateral infiltration (84%), lower lobe predominance (60%), and either confluent (56%) or patchy (33%) consolidation. Pleural effusion occurred in 24% of the patients. Complete resolution of chest roentgenography took from 8 to 42 days with a mean of 20 days. The response of fever to treatment with erythromycin took from 1 to 6 days with a mean of 3 days. There were no life threatening pulmonic or extrapulmonic complications. PMID- 1933625 TI - In vivo study of fluoride chewing gum for the remineralization of human root lesions. AB - The purpose of this study was to study the efficacy of a fluoride-containing chewing gum (0.1 mg F/stick chewed 5 x/day) in the remineralization of artificial caries lesions in abraded root surfaces compared to sorbitol-containing chewing gum and a no gum control group in vivo. Root specimens were cut from human root surfaces and polished. The specimens were demineralized in a buffered lactate solution with low concentration of fluoride in order to preserve an intact surface layer. Six healthy subjects wore mandibular Hawley-type appliances containing up to fourteen slabs for each of one control and two experimental periods. The experimental protocol included chewing five pieces of gums per day and brushing with fluoride-free dentifrice for each 21 days period. All three regimens were analyzed for fluoride uptake and microradiography. The results indicate that fluoride-containing chewing gum has a highly significant fluoride uptake and remineralization compared to sorbitol gum and control regimens, suggesting that fluoride chewing gum may provide another vehicle for fluoride delivery. PMID- 1933624 TI - Multifocal atrial tachycardia as a prognostic indicator in patients with severe chronic obstructive pulmonary disease requiring mechanical ventilation. AB - The records of 121 patients admitted to the Medical Intensive Care Unit (MICU) of Chang Gung Memorial Hospital with severe chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation were reviewed retrospectively. Eighty seven percent (20/23) of the patients with multifocal atrial tachycardia (MAT) expired during their ICU admission in contrast to 23.5% (23/98) of those without MAT. The only differences between these two groups were incidence of cor pulmonale, and right axis deviation, right bundle branch block, pulmonale P in electrocardiogram. MAT might be considered as a grave prognostic sign in patients with COPD severe enough to require mechanical ventilation. PMID- 1933626 TI - [Significant risk factors of attempted suicide in Chang Gung Memorial Hospital Keelung]. AB - From September 1988 to December 1989, 50 patients who had attempted suicide were admitted to the Division of General Internal Medicine in Keelung Chang Gung Memorial Hospital. Thirty-seven of the patients were female; the average age was 39.6 years. Thirty-three were married. Thirty-six had children, the average educational level was 7.1 years. The mean monthly income per family member was close to that of the corresponding population. Nine patients had pre-existing chronic medical diseases. Five patients had pre-existing confirmed diagnosis of psychosis. Thirty-nine patients had abnormal personality disorders or certain personality traits. Statistically, age between 30-39, female, low educational level, pre-existing psychosis, and abnormal personality disorders or personality traits are probable significant risk factors of attempted suicide. PMID- 1933627 TI - [Evaluation of commercially available fluoride containing toothpastes]. AB - The role of fluorides in caries prevention has been well established in the epidemiological studies of fluoridated areas. Without water fluoridation, dentists in Taiwan face the challenge to optimize the use of other forms of fluoride products to reduce caries incidence. Toothpaste containing fluoride constitutes an effective and practical way of exposing teeth to fluoride on a regular basis. The present study evaluated 62 commercially available toothpaste products, of which 35 lacked a proper Chinese label and product information. Forty-one products contained fluorides which were sodium fluoride and/or sodium monofluorophosphate. Half of the children's toothpastes did not contain fluoride. The statement of CNS 439 only indicated that the fluoride concentration of the toothpaste was below 1000 ppm. More information about type of fluoride and its concentration must be provided for the user or dental professionals to make a proper selection. Parental supervision of their children's toothbrushing needs to be reinforced. Certain products used for dental hypersensitivity contained high concentrations of fluoride. Young children must be guarded from accidentally ingesting an overdose of fluoride. PMID- 1933628 TI - Simultaneous ectopic pregnancy with intrauterine gestation after in vitro fertilization and embryo transfer. AB - A case of combined intrauterine and tubal ectopic pregnancy is described following in vitro fertilization and the transfer of two four-cell and one two cell embryos. This phenomenon is known to be related to ovarian stimulation by gonadotropin therapy, and there is an increased risk with tubal disease. Techniques applied at the time of embryo transfer, the use of culture medium with 50% fetal cord serum to convey the embryos to the uterus, the catheterization method, and the position of the patient during transfer are presented. The risk of multiple pregnancies and combined intrauterine and ectopic gestations increases with increasing numbers of transfers and large volume of transfer medium. We would therefore recommend that after IVF-ET treatment in women with tubal disease, intensive care should be taken in the early follow-up period to rule out the possibility of ectopic pregnancy. In this case, a viable ongoing intrauterine pregnancy was confirmed after surgery for right ampullary ectopic pregnancy. And a 2925gm male in excellent condition was delivered by cesarean section without complications. PMID- 1933629 TI - Multiple brain abscesses as a complication of pulmonary arteriovenous fistula. A case report. AB - A case of pulmonary arteriovenous fistula (PAVF) complicated by brain abscess is presented. The incidence of this complication has been quoted to be 1-5%. After reviewing all inpatients in Chang Gung Memorial Hospital from 1977 to 1988, we found a total of 9 cases of PAVF; only one case of PAVF complicated by brain abscess was noted. PAVF is often asymptomatic in the early stage, and its diagnosis may sometimes be quite difficult. However, untreated PAVF tends to enlarge and become symptomatic. There is also a continuing risk of severe neurologic complications. For these reasons, early diagnosis and treatment are essential. In a case of brain abscess associated with unexplained hypoxemia and extra-cardiac murmur on auscultation, PAVF should be considered. PMID- 1933630 TI - [Occult neuroblastoma presenting with opsomyoclonus. A case report]. AB - The combination of opsoclonus, myoclonus, and ataxia in small children suggests the presence of an occult neuroblastoma, and simple laboratory tests rather than sophisticated neuroradiological procedures may point directly to that diagnosis. We described an 18-month-old boy who presented with opsomyoclonus. A small neuroblastoma arising from the left adrenal gland was found by abdominal CT scan and I-131 M. I. B. G. (Metaiodobenzylguanidine) scan. Three and a half years after tumor removal, moderate mental retardation and ataxia persisted without tumor recurrence. PMID- 1933631 TI - Finding the magic pill: INTACT revisited. PMID- 1933632 TI - Preventing progression of coronary atherosclerosis: beyond cholesterol lowering. PMID- 1933633 TI - Hypertriglyceridemia as vascular risk factor: findings of the international evaluation. PMID- 1933634 TI - Patterns of myocardial fibrosis in idiopathic cardiomyopathies and chronic Chagasic cardiopathy. AB - OBJECTIVE: To study the fibrillar nature and structural features of the collagenous interstitium of the myocardium in normal and cardiomyopathic human hearts, employing the picrosirius red technique and polarization microscopy. DESIGN: A survey, case series study. SETTING: Referral autopsy service at a university medical centre (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto). CASES AND METHODS: A total of 46 adult hearts obtained at autopsy were used: five control hearts without evidence of cardiac disease, nine hearts with dilated cardiomyopathy, five with hypertrophic cardiomyopathy, four with endomyocardial fibrosis affecting the left ventricle, and 23 with chronic Chagasic cardiopathy. Fragments of myocardial tissue were obtained from the equator of the left ventricular free wall, fixed in formalin, dehydrated, and embedded in paraffin. Sections were stained with a modification of the picrosirius red technique and examined using direct light and polarization microscopy. RESULTS: The findings in the control myocardium did not differ from those reported in the literature. The myocardium in both dilated and hypertrophic cardiomyopathies showed diffuse fibrosis varying in degree from one case to another, but present in all cases. The basic pattern was characterized by a diffuse increase in both endomysial and perimysial collagen thick fibres, particularly surrounding individual myocytes (endomysial sheath). The microscopic study of the cases of endomyocardial fibrosis showed a thickened fibrotic endocardium consisting predominantly of thick collagen fibres extending as a septum, corresponding to broad perimysial sheaths, into the myocardium. In the superficial muscle fibre bundles usually composed of atrophic fibres, there was an increase in thickness of collagen fibres in both the perimysial and endomysial connective tissue matrix. To a variable degree (but present in all cases) interstitial and diffuse fibrosis could be observed in the chronic myocarditis of Chagas's disease. This was manifested by a diffuse increase in the amount of thick collagen fibres surrounding muscle fibre bundles (perimysial matrix), varying in intensity from one area to another, and around intramural coronary vessels, combined with a less pronounced increase in the endomysial collagen matrix. CONCLUSIONS: These findings extend knowledge of the various expressions of interstitial myocardial fibrosis in the idiopathic cardiomyopathies and chronic Chagasic cardiopathy and perhaps provide insight into pathogenesis. Further research into the patterns and pathogenesis of myocardial fibrosis are needed in order to offer prevention and corrective forms of therapy of the fibrotic process. PMID- 1933635 TI - Dipyridamole-thallium imaging: minimum dose requirements. AB - A total of 372 consecutive dipyridamole-thallium studies were reviewed to determine if a relationship existed between the dose of dipyridamole administered and the likelihood that thallium images would show reversible defects. Men who received a dose of less than 31 mg were less likely to have thallium redistribution (P = 0.0001). Until the ideal study involving repeat testing with incremental dipyridamole doses on different days is carried out, the authors recommend that a minimal dose of 31 mg be administered for dipyridamole-thallium imaging. PMID- 1933636 TI - Anaphylactoid reaction during an infusion of recombinant tissue-type plasminogen activator for acute myocardial infarction. AB - Potentially life-threatening immediate hypersensitivity reactions are extremely rare among patients treated with thrombolytic agents for suspected acute myocardial infarction. A patient who developed a severe reaction during an infusion of recombinant tissue-type plasminogen activator is described. Potential causal mechanisms for the reaction could be related either to nonmedicinal additives or complement activation. Implications for treatment in the setting of acute myocardial infarction are discussed. PMID- 1933638 TI - The use of two-dimensional echocardiography during catheter ablation of the atrioventricular node. AB - Atrioventricular nodal catheter ablation has proved an effective option in patients with drug-refractory, uncontrolled, supraventricular tachyarrhythmias; however, many complications in the immediate post ablative period relate to direct myocardial damage due to the electrical current generated by the catheter. The authors used two-dimensional echocardiography in a 57-year-old female patient with recurrent uncontrolled rapid ventricular rates despite multiple antiarrhythmic medications, in an attempt to identify the sequence of events responsible for complications of the ablation procedure. The echocardiographic images showed evidence of an explosion: microbubbles outlining an expanding force were seen which, if contained in a confined space such as the coronary sinus, might explain previously observed mechanical damage. Two-dimensional echocardiography may be useful for continual monitoring of catheter position during ablation. PMID- 1933637 TI - Arrhythmogenic right ventricular dysplasia with massive involvement of the left ventricle. AB - A 30-year-old male died suddenly after two years of clinically progressive episodes of recurrent ventricular tachycardia. In spite of recurrent episodes of palpitation, the patient had never shown signs or symptoms of heart failure before death. Post mortem examination revealed massive left ventricular involvement in addition to complete absence of myocardial tissue in the right ventricle, replaced by adipose tissue. This case illustrates that patients with arrhythmogenic right ventricular dysplasia may die of arrhythmia before failure of the left ventricle. PMID- 1933639 TI - Balloon expandable stents for acute closure post failed coronary angioplasty: case report and review of the literature. AB - Abrupt closure of a dominant right coronary artery occurred in a patient 1 h post coronary angioplasty. Angiography revealed a long spiral dissection involving the mid to distal segment of the right coronary artery. Four intracoronary balloon expandable stents were deployed to 'tack up' the dissection and recanalize the occluded artery. Six month follow-up angiography revealed continued patency of the stented segment. Balloon expandable stents may be an effective alternative to coronary bypass surgery in the treatment of acute closure following coronary angioplasty. PMID- 1933640 TI - Characteristics of the fast and slow components of the response to noradrenaline in rat aorta. AB - The fast and slow components of the response to noradrenaline in rat aorta were studied to assess their relative contribution to the total mechanical response. The fast component, the magnitude of which varied with the concentration of noradrenaline in a dose-dependent manner, was shown to be dependent on release of calcium from intracellular stores. In calcium-free medium with ethylene glycol bis-(beta-aminoethylether) N,N,N',N-tetra-acetic acid (EGTA) a noradrenaline challenge (1 microM) produced a transient increase in force which faded in about 10 mins. Addition of calcium at this point produces a slow component of similar amplitude to the total response to noradrenaline. Recycling of calcium through the intracellular store does not appear to play an important role under these experimental conditions, since the presence of noradrenaline in the bath prevented its refilling. It is concluded that extracellular calcium by itself (ie, the slow component) can account for the total contractile response to noradrenaline in rat aorta. PMID- 1933641 TI - Inotropic interventions and myocardial force-interval relation: a quantitative approach. AB - OBJECTIVES: To analyze inotropic influence on the early and late phases of cardiac sarcoplasmic reticulum calcium loading. DESIGN: Papillary muscles with parallel edges and no evidence of tissue branching were selected from the heart. Only muscle preparations that maintained stable passive diastolic and developed forces were used for analysis. Muscles were stretched to their maximum length and stimulated at 0.2 Hz. The early and late phases of sarcoplasmic reticulum calcium loading were evaluated quantitatively by mathematical fitting of the force interval relation. Increasing the extracellular calcium or decreasing the extracellular sodium was used to increase the inotropic state. ANIMALS: Right ventricular papillary muscles were isolated from female Wistar rats weighing 200 to 220 g. Electrical stimulation and data acquisition were controlled through a microcomputer. MAIN RESULTS: Increasing the extracellular calcium concentration from 0.5 to 1.0 mM produced a 90% increase in developed tension. This was accounted for by a 41% increase in the early phase of sarcoplasmic reticulum loading and a 29% increase in the late phase. A 20% reduction in the extracellular sodium concentration increased contractile force 100% and shifted the force-interval curve to the left. This was accounted for through an increase in both early and late phases of sarcoplasmic reticulum loading. CONCLUSION: These results are consistent with the current model of excitation-contraction coupling and clearly indicate that various positive inotropic interventions have selective effects on each process of the force-interval relation that cooperatively interact with each other. Mathematical fitting of data clearly improves the quantitative aspect of the force-interval response. PMID- 1933642 TI - Gadolinium-enhanced MRI of intracranial lesions. A review of indications and results. PMID- 1933643 TI - Distribution of metastases in breast carcinoma: CT evaluation of the abdomen. AB - To determine the frequency and distribution of extrahepatic and extraskeletal metastases in patients with breast carcinoma, the abdominal CT scans of 260 consecutive patients were systematically evaluated. Extrahepatic and extraskeletal metastases were demonstrated in 26 patients (10%). Confirmation of findings was made by biopsy, autopsy, or by demonstration of progression or regression of disease. Twelve patients (4.6%) demonstrated metastases to the stomach, eleven of whom presented with a linitis plastica pattern. Retroperitoneal and/or mesenteric adenopathy was noted in 10 patients (3.8%), of whom three demonstrated associated hydronephrosis and one demonstrated associated biliary obstruction. Ascites was seen in 14 (5.4%) and peritoneal carcinomatosis in 7 (2.6%). Genitourinary involvement included metastases to the kidney (one case), ureter (one), and uterus (one). Direct invasion of the diaphragm by adjacent pleural metastases (two cases) as well as a soft tissue metastasis (one case) was also demonstrated. Metastases to the ovaries, adrenals, or pancreas could not be identified. Although lesions to the liver and skeleton account for the largest group of metastases from breast carcinoma seen in the abdomen, one should be aware of the potential for other locations of metastatic disease. PMID- 1933644 TI - Perineural extension of nasopharyngeal carcinoma into the posterior cranial fossa detected by magnetic resonance imaging. AB - We report a case with perineural extension of carcinoma arising from the nasopharynx. Magnetic resonance (MR) imaging with gadolinium-DTPA enhancement detected subtle but evident findings of perineural tumor extension through the jugulare foramen into the posterior cranial fossa. PMID- 1933645 TI - MR imaging of middle cerebral artery occlusion without cerebral infarction. AB - Magnetic resonance (MR) images of 12 patients with angiographically proven middle cerebral artery (MCA) occlusion were analyzed, retrospectively. In three of the 12 patients, cerebral infarctions related to the MCA occlusions were not evident. Two of the three patients were cases of atherosclerotic occlusion and the remaining patient had an acute thromboembolism. In all of the occluded M1 portions of the MCA the flow void was absent and there were isointense linear structures, with or without a hyperintense component in the Sylvian vallecula, on T1-weighted images. For nine of the 12 patients, the absence of flow void in the ipsilateral Sylvian fissure was evident on the T2-weighted images. Therefore, even in cases with no evidence of a cerebral infarction, the presence of flow void in the Sylvian vallecula and Sylvian fissure must be searched for in routine reviews of MR images. If MR imaging can be obtained on an emergency basis, appropriate interventional therapy may be immediately initiated. PMID- 1933646 TI - Infarcted appendiceal carcinoid. CT appearance mimicking appendiceal abscess. AB - A unique case of an infarcted carcinoid of the appendix is presented in which the computed tomography (CT) and clinical findings mimicked an appendiceal abscess. Though unusual, this possibility and appearance should be familiar to the radiologist particularly if percutaneous drainage is considered. PMID- 1933647 TI - High-resolution computed tomography of Japanese summer-type hypersensitivity pneumonitis. AB - The high-resolution computed tomographic (CT) manifestations of Japanese summer type hypersensitivity pneumonitis in eight patients were correlated with those of their chest radiography and with their histological findings. Histologically proven small granulomas were clearly demonstrated on CT as miliary opacities in five patients whose chest radiographic findings were normal. In two patients, these abnormalities were observed both by CT and chest radiography. High resolution CT provides detailed morphological information about the lung parenchyma; it is an excellent means of following the clinical courses of hypersensitivity pneumonitis. CT is particularly useful for detecting persistent granulomas when symptoms subside and chest radiography becomes normal or nearly so. PMID- 1933648 TI - Computed tomography of congenital spondylolisthesis of the sixth cervical vertebra. AB - Congenital anomalies of the cervical spine occur relatively commonly. An interesting anomaly is congenital spondylolisthesis of the sixth cervical vertebra. We are presenting a case of this anomaly as imaged with plain radiography and computed tomography. We have also reviewed the previous literature and attempted to clarify distinctions between bilateral cervical spondylolysis with spondylolisthesis and other cervical spine lesions. PMID- 1933649 TI - Respiratory gating in magnetic resonance imaging: improved image quality over non gated images for equal scan time. AB - Magnetic resonance image quality is adversely affected by respiratory (RESP) motion during the scan. Respiratory gating improves magnetic resonance image (MRI) quality and removes artifacts, but has not been widely used, as RESP gating increases scan time. Our RESP-gating device was used to study scan time versus improvement in image quality using various gating modes; with and without combined electrocardiographic (ECG) gating. When RESP scans were acquired for the same time as non-gated scans, by using a wide RESP-gating window bracketing end expiration and a reduced number of pulse sequence repetitions, substantial improvement in image quality (over non-gated scans) resulted, despite the inferior statistical content of the acquisition. PMID- 1933651 TI - Radiographic imaging in assessment of combined manubriosternal and spinal fracture. AB - Deceleration injuries combined with hyperflexion of the torso as seen in motor vehicle accidents can result in combination of sternal and spinal fractures. This type of injury is associated with abnormalities of the soft tissue structures of the thorax. This publication reviews a case report of a deceleration injury and emphasizes the imaging modalities necessary to evaluate this constellation of abnormalities. PMID- 1933650 TI - MR imaging of pituitary hypertrophy due to juvenile primary hypothyroidism: a case report. AB - We present a case of pituitary hypertrophy due to juvenile primary hypothyroidism with subsequent return to normal size after therapy. This clinical entity is well known, but there are few reports on its magnetic resonance (MR) findings. We stress the usefulness of Gadolinium-DTPA-enhanced (Gd-DTPA-enhanced) MRI in the differential diagnosis of pituitary hypertrophy and pituitary adenoma. PMID- 1933652 TI - MRI in hyperparathyroidism requiring reoperation. AB - A 34-year-old woman presented with persistent hyperparathyroidism (HPT) following primary surgical removal of a hypertrophied parathyroid gland. Reevaluation ultrasound (US), computed tomography (CT), and parathyroid scintigraphy studies were negative for parathyroid adenoma. Magnetic resonance imaging (MRI) clearly identified an ectopic parathyroid adenoma within the lateral carotid sheath. Uncomplicated surgical extirpation of the adenoma was accomplished. We discuss the role of US, CT, parathyroid scintigraphy, and MRI in recurrent HPT. PMID- 1933653 TI - CT appearance of mesenteric saponification. AB - Although saponification of the pancreas is a frequent finding on computed tomography, saponification of extrapancreatic mesenteric sites has not been previously recognized. A case is presented of acute pancreatitis in which serial scans over a four-year period documented calcifications in old extrapancreatic phlegmons. Saponification from pancreatitis should be considered in the differential diagnosis of mesenteric calcifications. PMID- 1933654 TI - Coexistent adenocarcinoma and microcystic adenoma of the pancreas. AB - A case with coexistent pancreatic adenocarcinoma and microcystic adenoma is presented. These diagnoses were suspected on the basis of their computed tomography (CT) appearances and confirmed with CT-guided fine-needle aspiration. PMID- 1933655 TI - Uterine perforation by an intracavitary tandem: CT demonstration. AB - Perforation of the uterus by a tandem device is an important complication of intracavitary radiotherapy for cervical carcinoma. Although the sonographic appearance of this complication is well recognized, its demonstration by computed tomography (CT) has been reported in only a single case. We report a second case and discuss the CT findings. PMID- 1933656 TI - A 31-year-old white man with a sclerotic lesion of L1. PMID- 1933657 TI - Computer assisted patient education in the ambulatory care setting. PMID- 1933658 TI - Knowledge acquisition and knowledge representation in a rule-based expert system. AB - It is important to understand and describe how nurses make diagnostic decisions. This article describes the process by which knowledge is acquired and represented in a rule-based expert system for nursing diagnosis. Knowledge acquisition was obtained by tapping the expertise of clinical nurse specialists who were able to articulate the elements present in their diagnostic decisions. Knowledge representation was achieved using a commercially-available software package. VP Expert (Berkeley, CA). The clinical nurse specialists contributed many of the heuristics in the determination of self-care deficit as a nursing diagnosis. Three models of rules for the determination of self-care deficit, bathing are provided. These models represent a method for discriminating between levels of patient dependence. A description of rules that define specific causes, such as immobility are also included. They will be tested in the clinical setting. PMID- 1933659 TI - Preparing nurses to use microcomputers for the work of management. AB - Communications and information systems are expanding rapidly in health care organizations today. That nurses must not only be computer literate but also consumers of information technologies emerges as a professional imperative. This is especially true for nurses in management and administration. Therefore, exposing them to current technologies becomes crucial in their academic experience. Educating students to use business software applications and to understand their output will yield a leading edge to those preparing for management decision-making. PMID- 1933660 TI - Establishing a nursing informatics program. AB - Nursing informatics is the synthesis of nursing science, information management science, and computer science to enhance the input, retrieval, manipulation, and/or distribution of nursing data. The literature abounds with articles stressing the unmet computer needs of nurses. Nurses must go beyond knowing computer terms and following basic program commands; they must be informatics competent. This article proposes five courses in nursing informatics to enhance all areas of nursing: practice, administration, education, and research. PMID- 1933661 TI - Identifying and relating nurses' attitudes toward computer use. AB - The purpose of this study was to measure nurses' attitudes toward computer use based on an adaptation of Vroom's expectancy theory, and identify variables that may correlate with these attitudes. Content validity and reliability for internal consistency were determined for the developed attitude questionnaire. Nurses' individual characteristics and computer-use satisfaction, beliefs, and motivation were correlated. Data analysis revealed that nurses' attitudes were significantly related (satisfaction to beliefs, r = 0.783, p less than 0.001; satisfaction to motivation, r = 0.598, p less than 0.001; and beliefs to motivation r = 0.651, p less than 0.001), supporting the model based on Vroom's expectancy theory. Computer knowledge significantly related to computer-use beliefs (r = 0.229, p less than 0.05). Length of computer experience (r = -0.265, p less than 0.05) and nursing experience (r = -0.239, p less than 0.05) related negatively to nurses' computer-use satisfaction. PMID- 1933662 TI - Ocular pharmacokinetics of dacarbazine following subconjunctival versus intravenous administration in the rabbit. AB - The authors assessed the ocular toxicity and pharmacokinetics of subconjunctivally and intravenously administered dacarbazine in New Zealand white rabbits. Nine rabbits received a subconjunctival injection of 5 mg (three animals), 10 mg (three animals) or 25 mg (three animals) of dacarbazine in 0.5 mL of sterile water; 10 mg was found to be a well-tolerated dose. This dose was given as a bolus to 42 other rabbits either subconjunctivally (21 animals) or intravenously (21 animals). In both groups the dacarbazine concentrations in the ocular humours, serum and urine were measured by means of high-pressure liquid chromatography at 0.5, 1, 2, 4, 8, 12 and 24 hours, three animals being assessed at each interval. The peak serum levels of the drug were similar with the two routes of administration. The mean peak dacarbazine levels in the aqueous humour and vitreous humour after subconjunctival administration were 250 to 380 times those achieved after intravenous administration. The bioavailability of the drug over 24 hours was 107 micrograms/h.mL in the aqueous and 34 micrograms/h.mL in the vitreous after subconjunctival administration, compared with 0.65 and 0.14 micrograms/h.mL respectively after intravenous administration. Our results provide a solid pharmacokinetic basis for considering subconjunctivally administered dacarbazine in the treatment of human ocular melanoma. PMID- 1933663 TI - Homonymous hemianopic field defects and driving in Canada. AB - Significant functional impairment due to loss of visual field may seriously compromise the safe operation of a motor vehicle. The variable degree of recovery from homonymous hemianopic field defects and the lack of standardized provincial licensing guidelines on visual field defects further compound the difficulty in managing such patients. We reviewed the records of 60 patients with homonymous hemianopic field defects who were followed for an average of 27 months. The ability of the patients to meet the current provincial licensing standards was evaluated on presentation and over the follow-up period. On presentation 34 patients (57%) did not meet the minimum field requirements for an unrestricted license in any province or territory. At the most recent follow-up visit 20 patients (33%) had functional improvement, as measured by their ability to meet the requirements of more regions than they could initially. Four patients (7%) became functionally worse. Patients with homonymous hemianopic field defects should be followed for at least 2 years. The physician should inform the patient that a significant visual disability exists and advise him or her to cease driving when minimum standards are not met. PMID- 1933664 TI - Ocular anomalies in anencephaly: a clinicopathological study of 11 globes. AB - Eleven globes of seven anencephalic infants with a gestational age of 36 to 41 weeks were examined pathologically. Atrophy of the ganglion cell and nerve fibre layers of the retina was found in all cases; optic nerve atrophy was noted in all 10 specimens in which the optic nerve was identified. In addition to findings attributable to immaturity, including persistent pupillary membrane (in 10 globes) and incomplete formation of the anterior chamber angle (in 5), we noted retinal dysplasia (in 4), colobomata (in 2) and proliferative retinopathy (in 1). Uncommon or previously undescribed abnormalities in association with anencephaly included cystic malformations of the meninges, sclera and globe (in one case each). PMID- 1933665 TI - Glaucomatous optic nerve atrophy: the circumlinear vessel revisited. AB - Baring of a circumlinear vessel, or gap sign, is a sign of glaucomatous optic neuropathy that can be rapidly assessed during direct ophthalmoscopy. We previously found a significant association between the presence of this sign and the diagnosis and status of visual field defects. In the current study we followed this same group of patients for a mean of 78 months. The rate of agreement between two independent observers for the presence or absence of a circumlinear vessel was 79%, and the intraobserver rate was 71%. The corresponding rates for the presence of a gap sign were 84% and 90%. The presence of baring was significantly associated with development of a visual field defect in the glaucoma suspect group (p = 0.0105). The development of a gap sign in photographs taken approximately 6 years later was significantly associated with clinical progression of the appearance of the disc or the visual field defect (p = 0.0142). We conclude that patients with baring of a circumlinear vessel should be closely monitored for the development or progression of the glaucomatous process. PMID- 1933666 TI - Visual prognosis in central serous choroidopathy: residual Amsler grid changes. AB - To assess residual changes on Amsler grid charting in central serous choroidopathy, 30 patients (34 eyes) with the disorder were followed from the time of onset of symptoms to the time of resolution of the disease. A total of 28 eyes, including all 3 with an acuity of 6/6 or better, had Amsler grid changes at presentation, compared with 13 eyes at the last follow-up visit. Significantly more patients with a disease duration of more than 8 weeks than those whose disease lasted 8 weeks or less had residual changes (p less than 0.01). Overall, 41% of the eyes had a final acuity of less than 6/6 or a residual change or both. PMID- 1933667 TI - Schnyder's crystalline corneal dystrophy in association with hyperlipoproteinemia: histopathological and ultrastructural findings. AB - A 61-year-old man with Schnyder's crystalline corneal dystrophy showed a slight reduction in vision during 16 years of observation. Plasma lipoprotein analysis done 10 years after presentation showed type IIA hyperlipoproteinemia, which was also detected in one of four siblings examined, none of whom showed the characteristic corneal dystrophy. Electron microscopic studies on corneal biopsy specimens from the patient showed abundant crystalline material and vacuoles predominantly in the superficial corneal stroma, with occasional keratocytes and rare basal epithelial cells containing laminated structures. The findings of a focal continuity between the trilaminar membrane around some of the stromal vacuoles and the plasmalemma of the keratocytes as well as dissolution of the plasmalemma in other keratocytes are consistent with the hypothesis of a local cellular role in the development of this corneal disorder. PMID- 1933668 TI - Serous macular detachment in lymphoproliferative disorders. AB - Two patients, one with Hodgkin's disease and the other with non-Hodgkin's lymphoma, presented with bilateral diminution of vision. Examination showed bilateral serous detachment of the macula. To our knowledge, this is only the second report in the literature of serous detachment of the macula in lymphomatous disorders. PMID- 1933669 TI - Anterior segment necrosis associated with endogenous endophthalmitis secondary to group C streptococcal septicemia. AB - Anterior segment necrosis following ocular infections and endophthalmitis secondary to group C streptococcal infection are both rare. We report a case of unilateral anterior segment necrosis associated with bilateral metastatic group C streptococcal endophthalmitis in a 68-year-old black man with multiple systemic disorders complicated by culture-confirmed group C streptococcal septicemia and endocarditis. Pathological examination of the left eye at autopsy demonstrated necrosis of the anterior segment involving the cornea, iris, lens and ciliary body. The right eye showed signs of mild residual inflammation. To our knowledge anterior segment necrosis has not previously been described in association with group C streptococcal endophthalmitis. PMID- 1933670 TI - Learning the invariants of a perceptual motor skill. AB - The concept of invariant relative timing has typically been associated with the concept of a generalized motor programme. The present study approaches the phenomenon of invariant relative timing from the perspective of learning. The underlying question of concern for this study was, "What is learned." The specific question was whether relative timing is one of the essential properties of movement that is learned during skill acquisition. In the present experiment, subjects were given extensive practice in learning to track and reproduce a criterion waveform using a joystick control for their response. In order to test whether subjects learn the relative timing of a movement, they were transferred to tracking waveforms that were identical to the criterion in terms of relative timing, but different in terms of absolute timing. Measurements were taken on all waveforms in two conditions: (a) in a pursuit tracking condition where subjects were temporally constrained by the stimulus, and (b) in a reproduction condition where subjects' timing was not constrained. The outcome from both conditions gives support to the idea that humans learn invariant relative timing during the acquisition of a motor skill. PMID- 1933671 TI - Concurrent task interference in stutterers: dissociating hemispheric specialization and activation. AB - Using all four combinations of hand and foot, adult stutterers and nonstutterers performed a unimanual sequential finger tapping task together with a stimulus contingent foot responding task. The two groups were similar in that both demonstrated more dual-task interference when using the ipsilateral than contralateral limb pairs. Contrary to a prediction based on a hypothesis that attributes stuttering to neural interference due to an ungated or unregulated activity flow between the hemispheres, stutterers did not show more interference than nonstutterers when using the contralateral limb pairs. The groups did differ, however, in terms of finger tapping interference associated with right- versus left-foot concurrent task responding. Nonstutterers showed more interference when using the left than right foot. This was interpreted in terms of the attentional demands that the foot responding task placed on a system with an inherent left-hemisphere attentional bias. The lack of a reliable difference in stutterers with respect to interference by the two feet is consistent with indications from other research that stutterers have a relatively labile system of hemispheric attention or activation. The results of the study are placed into the context of a general model of the brain mechanisms associated with stuttering. PMID- 1933672 TI - Neither pictures nor propositions: what can we learn from a mental image? AB - In an earlier paper, we reported that subjects have great difficulty in finding alternative construals of their own mental images. In the present paper, we examine how subjects can nonetheless learn from their mental images. We argue that mental images, like percepts, are meaningful depictions. As such, mental images do depict appearance but are also inherently understood in a certain way, and this understanding influences the phenomenal appearance of the represented form. This, in turn, governs what the form will be seen to resemble and what the form is likely to call from memory. We report four experiments in support of this view. In each experiment, subjects are briefly shown outline shapes and asked to form a mental image of each shape. Subjects are then asked what familiar form the imaged shape resembles. Subjects routinely find target shapes in their images when the target is compatible both with the imaged geometry and with how that geometry is organized and understood. When the sought-for target is compatible with image geometry but not with how the image is understood, subjects reliably fail to find the target shape in their images. PMID- 1933673 TI - Binocular unmasking with vertical disparity. AB - We recently found (Schneider, Moraglia, & Jepson, 1989) that the contrast threshold for the detection of a visual signal in a noisy background can be considerably lower when binocular cues are available then when monocular cues only are present. Here, we investigated the occurrence of binocular unmasking with vertical interocular disparities. Subjects reported about the presence of Gabor signals in fields of two-dimensional broadband Gaussian noise surrounded by a frame of uniform noise. They saw these stimuli through a stereoscope; in all cases, the right-eye noise field was vertically displaced relative to the left one in either an upward or a downward direction, by up to 67.6'. In one condition, the right-eye signal was displaced by an amount equal to that of the noise, so that no opportunities for binocular unmasking existed; in the other, it appeared in exactly corresponding locations in the two fields--here, binocular disparities could be used to unmask the signal. Enhanced signal detectability, by up to 12.7 dB, was observed in the latter case for both directions of displacement, but only for displacements of 13.52' and only when the signal's orientation was horizontal. We argue that these effects result from the summation of monocular inputs carried out by linear binocular mechanisms. PMID- 1933674 TI - Occupation and handedness: an examination of architects and mail survey biases. AB - Handedness among architects was determined by mail survey. Contrary to previous reports, no evidence was found of an excess of left-handers among a sample of 236 fully qualified male architects and 78 male architectural students. A second study examined whether the use of mail surveys systematically biases the returns of handedness questionnaires. For this, questionnaires were sent to 1,017 university students. No evidence was found for a bias amongst those who did and did not reply to the initial questionnaire. These results strengthen the findings of the first study. PMID- 1933675 TI - [Spatial representation of a two-dimensional pattern]. AB - The purpose of this study was (a) to determine if vision and kinesthesis contribute differentially to the coding of a specific two-dimensional pattern and (b) to identify the effect of repetition on the spatial representation of this pattern. The reproductions of a specific pattern presented visually were compared with those of a pattern presented kinesthetically. The results showed that vision and kinesthesis had contributed equally to the coding of the directional components of the pattern. However, there was dominance of visual information over kinesthetic information when coding the distance between the intersecting points of the pattern, especially at the beginning of the process. Generally speaking, the visual or kinesthetic repetition, or both, have increased favourably the precision with which a specific pattern was reproduced in distance and direction. PMID- 1933676 TI - Sex, handedness, mathematical ability, and biological causation. AB - An important part of Benbow's (1988) assertion that sex differences in mathematical ability are primarily due to biological factors is the link between a trait that is assumed to reflect differences in brain organization (left handedness) and mathematical giftedness. It is shown that the link between mathematical giftedness and an increased prevalence of left-handedness is not convincing. However, Benbow's (1986) data do show a convincing link between strong right-handedness and the lack of mathematical giftedness, in agreement with Annett and Manning's (1990a, 1990b) recent work. PMID- 1933677 TI - Atrial myxoma--a dramatic tale! PMID- 1933678 TI - A cardiac arrest policy. AB - The following article describes the process in the development and implementation of an Operating Room's Cardiac Arrest Policy. The actual guidelines and forms developed are presented. PMID- 1933679 TI - The surgeon and the nurse share the blame: a case of a retained sponge. PMID- 1933680 TI - Projecting ourselves as professionals. PMID- 1933682 TI - Neuronal degeneration in aging and disease. Proceedings of a symposium. London, Ontario, October 4-5, 1990. PMID- 1933681 TI - Angioscopy. AB - Over the past three to four decades vascular surgery has experienced increasing interest and rapid growth. This surgical specialty continues to show an annual increase in the number of procedures performed, and demonstrates increasing use of innovative technology. The author explains how the angioscope has emerged as a potentially powerful diagnostic tool for today's vascular surgeon. Its implications, complications and the post operative nursing care for the patient undergoing angioscopy will be discussed. PMID- 1933683 TI - Effects of dopamine denervation on striatal peptide expression in parkinsonian monkeys. AB - In cynomolgus monkeys rendered parkinsonian by systemic injection of MPTP, severe cell losses were noted in the ventrolateral portion of the substantia nigra pars compacta (SNc), compared to a relative sparing of neurons in the ventral tegmental area (VTA) and dorsomedial portion of SNc. Most spared neurons in the SNc-VTA complex were found to contain the calcium binding protein calbindin (CaBP). At striatal levels the dopaminergic (DA) innervation, as visualized by tyrosine hydroxylase immunoreactivity, was markedly reduced in the 'sensorimotor' territory, variably affected in the 'associative' territory, and relatively well preserved in the 'limbic' territory. The immunoreactivity for enkephalin was enhanced and that for substance P was decreased in the sensorimotor territory, whereas the inverse was observed in the limbic territory. The distribution of the two peptides was highly heterogeneous in the associative territory. These findings suggest that the influence of the DA input on peptide expression varies from one striatal territory to the other, and that CaBP may protect midbrain DA neurons from MPTP toxicity. PMID- 1933684 TI - Reactions of the immune system in chronic degenerative neurological diseases. AB - Elements consistent with a cell mediated immune response were identified immunohistochemically in amyotrophic lateral sclerosis (ALS) spinal cord and Alzheimer disease (AD) hippocampus. T helper/inducer and cytotoxic/suppressor lymphocytes were detected in affected tissues in both diseases. In addition, abundant reactive microglia were found expressing the major histocompatibility glycoproteins HLA-A,B,C and HLA-DR, as well as receptors for the Fc chain (Fc gamma R1), for complement 3 and 4, and for vitronectin. In AD, the complement proteins C1q, C4d, C3d and C5b-9 were found on dystrophic neurites, neuropile threads and some neurofibrillary tangles. In ALS, the only complement proteins identified were C4d and C3d. The integrin ligands vitronectin and ICAM-1 were also identified in affected tissues in both diseases. PMID- 1933686 TI - Amyotrophic lateral sclerosis/parkinsonism/dementia: clinico-pathological correlations relevant to Guamanian ALS/PD. AB - In a recent report on the clinical and pathological features of Guamanian ALS/PD and post-encephalitic parkinsonism/ALS a number of similarities were described, notably in the distribution of neurofibrillary tangles throughout the nervous system. In this account additional pathological features which these disorders share (and which differ from classical ALS, Parkinson's and Alzheimer's diseases) are described. These include atrophy of the globus pallidus and the entire substantia nigra, viz. pars compacta and pars reticulata. Moreover, neither Lewy bodies nor senile plaques are features of the Guamanian and post-encephalitic disorders. The significance of these observations and their relationship, more generally, to parkinsonism, ALS and dementia are discussed. PMID- 1933685 TI - New approaches to the treatment of age-related brain disorders. AB - Two novel reversible enzyme inhibitors involved in monoamine metabolism are described. The novel and reversible inhibitors are the catechol-O-methyl transferase (COMT) inhibitors, Ro 40-7592 (3,4-dihydroxy-4'-methyl-5 nitrobenzophenone), and the monoamine oxidase type-B (MAO-B) inhibitor, Ro 19 6327 (N-(2-aminoethyl)-5-chloro-2-pyridine carboxamide HC1). These may be of special therapeutic benefit in Parkinson's and Alzheimer's diseases. PMID- 1933688 TI - Molecular interactions modulating neuronal survival and growth. AB - The extracellular environment of the neuron provides a heterogeneous milieu of survival and growth modulating molecular species subserving regulatory signals that operate in development, mediate activity-dependent enduring changes in synaptic connectivity, and promote or inhibit survival and axonal regeneration following insult. Parallel distributed processing networks in neurons, activated by these molecular species, can likely be recruited selectively to serve specific needs of the organism. PMID- 1933687 TI - Growth factors and lymphokines: modulators of cholinergic neuronal activity. AB - It is well known that various markers of the cholinergic synapse are altered in Alzheimer's Disease. Much interest is currently focussing on the evaluation of the possible efficacy of certain growth factors, especially nerve growth factor (NGF), to reduce or reverse cholinergic neuronal losses. Here we report that other growth factors (epidermal growth factor and insulin-like growth factor I) and a lymphokine, interleukin-2, are able to block acetylcholine release in the rat hippocampus. This suggests that while certain growth factors like NGF may have positive effects on the cholinergic neuron, others may act as "negative" factors on this neuronal population. PMID- 1933689 TI - Exogenous NGF affects cholinergic transmitter function and Y-maze behavior in aged Fischer 344 male rats. AB - Chronic ICV administration of NGF stimulates the activity of the cholinergic neuronal markers, HACU and ChAT, as well as the evoked release of both endogenous and newly synthesized acetylcholine in the brain of aging Fischer 344 male rats. However, the pattern of cholinergic phenotype stimulation indicates an age related differential regulation of ChAT, HACU, and ACh release between specific brain areas, with the largest effects found in the striatum. NGF treatment also increases the effectiveness of neurotransmission between basal forebrain cholinergic neurons and postsynaptic amygdaloid target neurons. The stimulation of central cholinergic transmitter function after NGF treatment affects behavior in a Y-maze brightness discrimination paradigm. NGF treatment does not affect the cognitive measure of brightness discrimination, but reduces the number of avoidance attempts, a measure of motor function. PMID- 1933690 TI - New biochemical insights to unravel the pathogenesis of Alzheimer's lesions. AB - Purification of amyloid plaque core proteins (APCP) from Alzheimer's disease brains to complete homogeneity and in high yield permitted its chemical fractionation and characterization of its components. APCP is mainly made of beta amyloid (beta A) and an assortment of glycoproteins (accounting for 20%) rich in carbohydrates compatible with N- and O-linked saccharides. When added to tissue culture of sympathetic and sensory neurons APCP and beta A inhibited neuritic sprouting, a reversible phenomenon at low doses. Higher concentrations of both substances kill the neurons in culture. APCP is significantly more toxic than beta A, suggesting the minor components may play an important role in increasing the toxicity of beta A. If the observed toxic effects of APCP in situ are occurring in vivo during the course of AD, then the accumulation of these extracellular proteins could be largely responsible for some of the neuronal death observed in this neuropathology. PMID- 1933691 TI - Anomalous gene expression in Alzheimer disease: cause or effect. AB - Altered chromatin conformation and increased amounts of aluminum have been observed in the brains of patients with Alzheimer disease. These factors have been shown to affect gene regulation. In this report, we describe how these changes may selectively alter the pool size of the human light chain neurofilament gene and play a fundamental role in the expression of this disease. PMID- 1933692 TI - Beta-amyloid protein in Alzheimer's disease. AB - Beta-amyloid protein, a 42-43 amino acid polypeptide, accumulates abnormally in senile plaques and the cerebral vasculature in Alzheimer's disease. This polypeptide is derived from a membrane-associated precursor which has several isoforms expressed in many tissues. The precursor protein is processed constitutively within the beta-amyloid domain, leading to the release of the large N-terminal portion into the extracellular medium. beta-amyloid protein may be toxic to certain neuronal cell types and its early deposition may be an important event in the pathogenesis of Alzheimer's disease. PMID- 1933693 TI - Chronic aluminum-induced motor neuron degeneration: clinical, neuropathological and molecular biological aspects. AB - The monthly intracisternal inoculation of young adult New Zealand white rabbits with low-dose (100 micrograms) aluminum chloride induces aggregates of phosphorylated neurofilament that mimics the intraneuronal inclusions of amyotrophic lateral sclerosis. The chronic progressive myelopathy and topographically-specific motor neuron degeneration that occurs in the absence of suppressions of neurofilament messenger RNA levels in this model contrasts with the acute fulminant encephalomyelopathy and nonspecific gene suppressions that occur subsequent to high-dose (1000 micrograms) aluminum chloride inoculations. Further analysis of this unique model of chronic motor system degeneration can be expected to provide additional insights into the pathogenesis of amyotrophic lateral sclerosis. PMID- 1933694 TI - Hereditary canine spinal muscular atrophy: an animal model of motor neuron disease. AB - Motor neuron diseases selectively produce degeneration and death of motor neurons; the pathogenesis of these disorders and the specificity for this population of neurons are unknown. Hereditary Canine Spinal Muscular Atrophy produces a lower motor neuron disease which is clinically and pathologically similar to human motor neuron disease: motor neurons dysfunction and degenerate. The canine model provides an opportunity to investigate early stages of disease when there are viable motor neurons still present and might be responsive to a variety of therapeutic interventions. The canine disease, like the human disease, is inherited as an autosomal dominant. The extensive canine pedigree of more than 200 characterized individuals permits genetic analysis using syntenic linkage techniques which may identify a marker for the canine trait and provide insights into homologous regions for study in human kindreds. PMID- 1933695 TI - Treatment of Alzheimer's disease: hopes and reality. AB - The relative failure of symptomatic therapeutic trials for Alzheimer's disease using non-selective cholinergic agonists brings about the need for longitudinal studies with parallel designs aimed at disease stabilization, using trophic substances or amyloid suppressors. PMID- 1933696 TI - Screening for cancer of the cervix. PMID- 1933697 TI - Physical inactivity among physicians. PMID- 1933698 TI - HIV infection among Quebec women giving birth to live infants. PMID- 1933699 TI - Canadian medicare: view from Utopia. PMID- 1933700 TI - Cognitive impairment in the elderly. PMID- 1933701 TI - Serious childhood injuries caused by air guns. PMID- 1933702 TI - Nintendo neck. PMID- 1933703 TI - Prevention of firearm-related injuries in Canada. PMID- 1933704 TI - Firearm-related injuries in Canada: issues for prevention. AB - We reviewed the available data on firearm-related injuries in Canada to suggest strategies for prevention in the context of the proposed amendments to the Criminal Code (Bill C-17) currently before Parliament. The risk of death from a firearm in Canada is equivalent to the risk of death from a motor vehicle crash. We discuss the risks associated with firearms with regard to suicides, homicides and "accidents." We also discuss the accessibility of firearms. This article builds upon a recently published update on the epidemiologic basis of the public health approach for the prevention of firearm-related injuries and deaths. The key to the etiologic approach to preventing such injuries and deaths is to view the incidents, regardless of their medicolegal circumstances, as having one factor in common: the discharge of a firearm. PMID- 1933705 TI - Insulin-dependent (type I) diabetes mellitus. AB - Insulin-dependent (type I) diabetes mellitus is a chronic disease characterized by hyperglycemia, impaired metabolism and storage of important nutrients, evidence of autoimmunity, and long-term vascular and neurologic complications. Insulin secretory function is limited. Cell membrane binding is not primarily involved. The goal of treatment is to relieve symptoms and to achieve blood glucose levels as close to normal as possible without severe hypoglycemia. However, even with education and self-monitoring of the blood glucose level, attaining recommended target values (plasma glucose level less than 8.0 mmol/L before main meals for adults) remains difficult. Human insulin offers no advantage in glycemic control but is important in the management and prevention of immune-related clinical problems (e.g., injection-site lipoatrophy, insulin resistance and allergy) associated with the use of beef or pork insulin. Therapy with one or two injections per day of mixed short-acting or intermediate-acting insulin preparations is a compromise between convenience and the potential for achieving target plasma glucose levels. Intensive insulin therapy with multiple daily injections or continuous infusion with an insulin pump improves mean glycated hemoglobin levels; however, it increases rates of severe hypoglycemia and has not been shown to decrease the incidence of clinically significant renal, retinal or neurologic dysfunction. Future prospects include automated techniques of insulin delivery, immunosuppression to preserve endogenous insulin secretion and islet transplantation. PMID- 1933706 TI - [Temporary incapacity and emotional problems]. AB - The author deals with temporary incapacity, as currently expressed by "sick leave." Minor psychiatric problems are involved more and more as a cause of temporary incapacity, and sometimes the duration of such leaves of absence is much longer than might be warranted by the nature of the problem. Challenges by paying agents and employers are more and more frequent. On the basis of literature of a very general nature the author distinguishes between a difficult personal situation, a symptom, an illness, functional limitations and invalidity, the last one being at the crossroads between medical, personal and social reasons. The author emphasizes the particular difficulties experienced by physicians faced with that kind of problem and describes the rapid intervention needed to deal with the underlying reasons for an obvious request for a leave of absence. PMID- 1933707 TI - Prostaglandin E2 gel for cervical ripening and labour induction: a multicentre placebo-controlled trial. AB - OBJECTIVE: To determine the effect of a single intracervical dose of prostaglandin E2 (PGE2) gel on cervical ripening and the need for subsequent labour induction with oxytocin. DESIGN: Multicentre randomized, double-blind, placebo-controlled study. SETTING: Tertiary care hospitals. PATIENTS: A total of 397 women met the inclusion criteria: gestational age of at least 36 weeks, parity of 3 or less, a Bishop score of 4 or less, intact membranes, an indication for induction, no contraindication to vaginal delivery, no history of cesarean section or major uterine surgery, no hypersensitivity to prostaglandins, no previous attempt at cervical ripening or induction, no vaginal bleeding and no fetal abnormalities. INTERVENTION: The experimental group (203 women) received a low dose (0.5 mg) of PGE2 in 2.5 mL of gel and the control group (194) 2.5 mL of a placebo gel intracervically. The observation period was 12 hours before further induction (with oxytocin) was attempted. OUTCOME MEASURES: Ripening effect of gel, need for induction with oxytocin, rate of labour induction, time from gel administration to delivery. RESULTS: Seventeen women could not be evaluated because induction was not attempted after the first 12 hours (in nine cases) or the induction attempt was delayed for 24 hours (in six); in the other two cases the gel was in place for only 2 1/2 and 4 hours respectively before cesarean section was required. The Bishop score 12 hours after the gel administration and the difference in the score from the time of admission to the end of the 12-hour observation period were significantly higher in the experimental group than in the control group (p less than 0.001). In all, 91 (46%) of the 196 patients in the experimental group went into labour within the 12-hour observation period, as compared with 21 (11%) of the 184 in the control group (p less than 0.001). When the women who required further induction were included the rate of successful induction was 85% (166 women) and 72% (132) respectively (p less than 0.004). The mean interval from the time of gel administration to delivery was smaller in the experimental group than in the control group (19.8 v. 24.1 hours respectively) (p less than 0.001). CONCLUSIONS: A single, low dose of PGE2 gel administered intracervically is a safe and reliable method of dealing with indicated but potentially difficult inductions. PMID- 1933708 TI - Chronic status patients in a university hospital: bed-day utilization and length of stay. AB - OBJECTIVE: To examine the lengths of stay of chronic status patients in an acute care hospital, to identify discharge stages that contribute to excessive stays, to estimate the length of stay at each discharge stage and to link hospital bed day utilization by the discharge stage to the experience of the patient. DESIGN: Two-year prospective cohort study. The number of hospital days retrospective to the date of the current admission were included in the analysis. SETTING: University hospital. PATIENTS: All 115 inpatients formally declared as achieving chronic status by July 31, 1987. OUTCOME MEASURES: Lengths of stay (total days and days at acute and chronic status) for chronic status patients, including those still in hospital at the end of the study period. Each bed-day was assigned to a discharge stage that corresponded to the patient's status. The disposition of each patient by the end of the study period was reviewed. RESULTS: The study population spent a total of 101 585 days in hospital. The total length of stay per patient was nearly four times that stated in the hospital's annual report, in which the figure was calculated only on the basis of discharge data. On average only 77.2 (8.7%) of the days were spent in acute care. The remaining days were at the chronic level: 24.1% were spent waiting for completion of an application to a long-term care facility, 25.3% for application approval and 41.9% for an available bed in the assigned long-term care institution. For 30 patients no initiation of the discharge process was ever undertaken. As the number of patients in each progressive discharge stage decreased, the wait per patient increased. By the end of the study period only 32 patients had been transferred to a public long-term care facility; 22 were still in hospital, and 35 had died waiting for placement. CONCLUSIONS: Although considered to be a useful measure of hospital efficiency, length of stay determined from discharge data creates an iceberg effect when applied to chronic status patients in acute care hospitals. Lack of access to the assigned resource is the most important reason for a delay in discharge. Interventions, whether undertaken at the patient, hospital or provincial level, must to some degree address this issue. Further study is required to determine which risk factors will predict lags at each discharge stage. Since our discharge staging reflects not only the experience of the patient but also the utilization of hospital bed-days and access to provincial resources, it provides a common language for clinicians, hospital administrators and systems planners. PMID- 1933709 TI - Adverse events temporally associated with immunizing agents: 1989 report. PMID- 1933710 TI - The molecular basis of hepatic lipase deficiency. PMID- 1933711 TI - Pancreatic extracts in the treatment of diabetes mellitus: preliminary report. 1922. PMID- 1933713 TI - The medical profession sets its sights on the gun-control issue. PMID- 1933712 TI - Report of a National Workshop on Screening for Cancer of the Cervix. PMID- 1933714 TI - About 2000 Dutch patients choose euthanasia annually, forum told. PMID- 1933716 TI - The Cree of northern Quebec: a different culture means a different type of practice. PMID- 1933717 TI - Practising in Chisasibi: the money is good, the experience is better. PMID- 1933715 TI - Separation will hurt Quebec health care system, Ottawa physician warns. PMID- 1933718 TI - Life on Aitutaki. PMID- 1933719 TI - Atlas. Skin lesions in HIV infected patients. PMID- 1933720 TI - HIV-associated pruritus. PMID- 1933721 TI - Antiretroviral therapy. PMID- 1933722 TI - HIV and safety: universal precautions. PMID- 1933723 TI - Kaposi's sarcoma. PMID- 1933724 TI - Psoriasis and Reiter's syndrome. PMID- 1933725 TI - Skin manifestations of HIV-1 infection in children. PMID- 1933726 TI - Fungal and mycobacterial skin infections. PMID- 1933727 TI - Clinical problems of syphilis in the presence of HIV. PMID- 1933728 TI - Bacillary (epithelioid) angiomatosis. PMID- 1933730 TI - Pathology of HIV-related skin disease. PMID- 1933729 TI - Warts and molluscum contagiosum. PMID- 1933731 TI - Cellular and biochemical dynamics of wound repair. Wound environment in collagen regeneration. PMID- 1933732 TI - Complications of wound repair. AB - In the consideration of wound healing and complications that impede its progress, one should keep in mind that detrimental factors generally affect more than one aspect of the repair process. Wound healing considerations should begin with a thorough history and physical examination upon a patient's first office visit. Factors that affect a patient's ability to heal successfully are listed in Tables 3 and 4. PMID- 1933733 TI - Wound healing in the elderly. AB - Wound healing in the elderly depends on the aforementioned risk factors and fundamental principles of wound management. Good results can be obtained through the realization that the elderly patient is an immunocompromised host requiring a prompt, definitive treatment based on a thorough history, physical examination and appropriate consultations with other health care professionals. PMID- 1933734 TI - Electrical stimulation for dermal wound healing. AB - The investigations of biologic actions (in vitro, animal, and human) demonstrated several effects that help explain why electrical stimulation works. Based on the latest scientific understanding of the wound healing process, one would expect that a therapy that decreases edema, debrides necrotic tissue, attracts neutrophils and macrophages, stimulates receptor sites for growth factors, stimulates growth of fibroblasts and granulation tissue, increases blood flow, stimulates neurite growth, induces epidermal cell migration, prevents postischemic oxygen radical-mediated damage, inhibits bacteria, and reduces numbers of mast cells ought to be beneficial for wound healing. Numerous human and animal efficacy studies confirm that electrical stimulation of the proper charge, density, and total energy causes dramatically improved healing of dermal wounds. As of this writing, no devices have yet been approved by the FDA for use in wound healing, although several devices approved for other indications are being used for this purpose. One device (the Staodyn Dermapulse) has undergone controlled animal and human testing, and an application requesting approval for treating dermal ulcers has been submitted to FDA. Taken together, the efficacy studies and the "mechanism of action" studies provide compelling, scientific evidence that electrical stimulation is safe and effective for promoting the healing of dermal wounds. PMID- 1933735 TI - Pathophysiology and treatment of diabetic foot ulcer. AB - The etiology of diabetic foot ulcers is reviewed. A combination of neuropathy, angiopathy, and biomechanical forces are shown to cause foot ulcers in the diabetic patient. A treatment regimen for the resolution of these ulcers is proposed. Early detection with meticulous care and a high level of suspicion for infection expedites patient care. Metabolic control of diabetes mellitus will also encourage more rapid resolution of the diabetic foot ulcer. Patient education and compliance provides significant results and decreases the incidence of ulceration. PMID- 1933736 TI - Pressure ulcers. AB - Progress in treatment of pressure ulcers over the past decade has contributed to our ability to more effectively treat problem ulcers. Through choice of the proper dressing, wound environment and cellular activity may be positively influenced and wound repair accelerated. Electrical stimulation, biologic implants, and growth factors are advanced forms of treatment that will become more accessible during the 1990s. Despite all the progress made, one must remember that these modalities are not substitutions for the care necessary to prevent the occurrence of pressure ulcers. Appropriate care and knowledge of available products are necessary to ensure the most effective treatment. PMID- 1933737 TI - Pressure ulcers. Physical, supportive, and local aspects of management. AB - Pressure ulcers are a common and serious problem predominately among elderly persons who are confined to bed or chair. Additional factors associated with pressure ulcer development include cerebrovascular accident, impaired nutritional intake, urinary or fecal incontinence, hypoalbuminemia, and previous fracture. Implementation of preventive measures, such as an in-depth assessment for mobility, a pressure-relieving device combined with adequate repositioning, and thorough evaluation for nutritional status and urinary incontinence, significantly reduce pressure ulcer incidence. If the pressure ulcer is a partial thickness (stage II) wound, the causative factors are probably friction or moisture. If the ulcer is full thickness (stage III and IV), it is secondary to pressure or shearing forces. The development of wound infection is the most common complication in the management approach. Osteomyelitis is not an uncommon occurrence and must be initially ruled out in all full thickness pressure ulcers. Surgical debridement of necrotic tissue is necessary prior to further treatment and assessments. Antibiotic therapy is indicated only upon evidence of infection (cellulitis, osteomyelitis, leukocytosis, bandemia, or fever). Topical pharmacologic agents may be used to prevent or treat infection but must be carefully controlled to avoid such adverse effects as toxicity to the wound, allergic reaction, and development of resistant pathogens. Proper use of occlusive dressings increase patient comfort, enhance healing, decrease the possibility of infection, save time, and reduce costs. A patient presenting an ulcer that fails to improve or, because of its size, will take a great deal of time to heal should be evaluated for surgical closure. PMID- 1933738 TI - Peripheral vascular assessment and its role in predicting wound healing potential. AB - Local perfusion is a critical factor in wound healing with substantially greater perfusion levels necessary to support healing than those required to maintain viable intact tissues. Clinical observations alone are not sufficiently reliable to assess healing potential particularly in the patient with known vascular compromise. This article reviews the more common noninvasive techniques for evaluating peripheral circulation and wound healing potential in the distal lower extremity. PMID- 1933740 TI - Child and adolescent psychiatry. PMID- 1933739 TI - Growth factor impact on wound healing. AB - Sixty thousand to 118,000 lower extremity amputations are performed each year in the United States. The combination of peripheral vascular disease and diabetes mellitus accounts for most cases, with diabetic patients representing 45% to 70% of all nontraumatic, lower extremity amputations. The 3-year survival rate after amputation is only 50%. As podiatric physicians, we are directly involved in limb preservation. Progress has occurred in both the diagnosis and treatment of lower extremity, chronic, nonhealing ulcers. An aggressive, comprehensive amputation intervention program is critical to those patients with refractory wounds to prevent the emotional, functional, and economic costs of limb loss. Recent developments in recombinant growth factors are making it possible to decrease the morbidity and mortality associated with defective angiogenesis, fibroblastic proliferation, collagen remodeling, and epithelial regeneration. Widespread use of growth factors will first occur in topical applications. Absorbable sutures, as well as impregnated bandages, are a likely method of delivering the growth factors to the wound site. Biotechnology companies are developing a stable formulation for bFGF topical application. Clinical trials have begun at various teaching hospitals across the United States for treatment of venous stasis ulcers. U.S. and European firms are collaborating to conduct the clinical studies required to obtain regulatory approvals leading to the sale of topical recombinant bFGF. Although U.S. approval is pending, European use of EFG in the healing of corneal incisions began several years ago. In the future, use of recombinant EGF topically with burn patients may permit earlier reharvesting of healed donor sites as well as coverage of larger graft areas. As some growth factors affect specific processes of healing and cell types, it may be necessary to combine growth factors for complex wounds. PDGF application in combination with other growth factors to incisional wounds may decrease postoperative complications with wound dehiscence while mediating inflammation and repair. In vivo experimental findings suggest that combinations of PDGF and insulin applied topically to wounds may increase the rate of wound repair in diabetics. It is also possible that even the normal healing process may be accelerated, thereby shortening postsurgical convalescence. Approval for internal administration of growth factors will require additional research and thorough clinical trials. The ability of TGF-beta to promote collagen formation may also relate to a metabolic condition such as osteoporosis, in which inadequate formation of collagen or other components of the bone matrix may contribute to pathogenesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1933741 TI - Recent developments in attachment theory and research. AB - The history and development of attachment theory are reviewed. Research has focused on four major patterns of attachment in infancy: one pattern of secure attachment and three patterns of insecure attachment (avoidant, resistant, and disorganized). These patterns have been shown to reflect different histories of parent-child interaction and affected subsequent development up to age eight. More recently, methods have been developed for identifying similar patterns of attachment in preschoolers, five to seven year olds and adults. Future research is likely to focus on the development of attachment patterns and their transmission from one generation to another. New data on the relationship between attachment and behaviour problems has generated mutual respect and collaboration between clinicians and researchers. PMID- 1933743 TI - Youth with conduct disorder: a challenge to be met. AB - Conduct disorder is one of the most common psychiatric disorders in children and adolescents between the ages of four and 16. This paper summarizes the literature on conduct disorder, from definition and diagnosis to treatment and prevention. In addition, it reports on the deliberations and recommendations of a group of clinicians and researchers who met at a retreat to discuss ways to improve the quality of treatment and develop prevention strategies for youth with conduct disorder. This retreat was held under the auspices of the Institute for the Study of Antisocial Behaviour in Youth. PMID- 1933742 TI - Adolescent female firesetters. AB - A retrospective study of the charts of 13 female adolescent firesetters revealed severe family and individual pathology. The parents had a history of separation, violence, alcohol and/or drug abuse, and inability to take care of the children. The girls had a long history of serious behavioural problems. Four girls had set one fire, six had set several fires within a period of a few days, three had a long-standing history of setting fires. The girls showed a lack of remorse or concern for their behaviours. PMID- 1933744 TI - Resilience and vulnerability in long term outcome of attention deficit hyperactive disorder. AB - Follow-up studies of children with attention deficit hyperactive disorder show that they continue to have problems with restlessness, over-activity, impulsive behaviour and inattention, often resulting in serious academic, social and emotional problems in adolescence. Outcome in adulthood generally falls into three groups: fairly normal outcome, persistent attentional, social, emotional and impulse problems, and serious psychiatric and/or social pathology. Factors affecting outcome include characteristics related to the child (for example, health, temperament, IQ) and characteristics of the family (for example, socioeconomic status, emotional and psychological aspects of the family, family composition and structure, and the larger social and physical environment. PMID- 1933745 TI - [Preliminary study of early sexual abuse]. AB - The long term effects of sexual abuse are often measured by measuring behaviours such as social adjustment, job stability and marriage. This study was conducted to add to these internal measures. Using a semi-prospective instrument adapted from G. Kelly's repertory grid, the adolescents' perceptions of themselves and significant others are measured. Three hundred and twelve female adolescents between the ages of 13 and 19 (average age = 16) participated in the study; 79 presented with non sexual behaviour disorders (delinquency, stealing, etc.), 56 presented with serious sexual behaviour disorders (prostitution, persistent sexual promiscuity) and 177 presented with no problems requiring psychosocial intervention. Various analyses (descriptive, multiple variance, regression analysis) showed that sexual abuse significantly affects many of the adolescents' perceptions. Sexually abused adolescents perceived their two real parents as less competent and their ideal mother and father as less protective than adolescents who had not been abused. In contrast, their perception of self and the ideal self was not affected by the sexual abuse, a finding which will spark discussion. PMID- 1933746 TI - Diagnostic utility of the Beck Depression Inventory with adolescent psychiatric outpatients and inpatients. AB - The utility of the Beck Depression Inventory (BDI) for differentiating adolescents with depressive disorders from adolescents with non affective psychiatric disorders was examined using a sample of 93 psychiatric outpatients and 26 inpatients. The Diagnostic Interview for Children and Adolescents (DICA) was administered to establish the patients' diagnosis. Psychiatric diagnoses were made by experienced clinicians who used all available information on the patient. The BDI scores discriminated between patients with depressive disorders and patients with non affective psychiatric disorders. This differentiation was true for boys and girls, outpatients and inpatients. The classification accuracy of the instrument was 75% at thresholds of 11 and 16 on the scale. The results indicate that the BDI is a useful instrument for screening for depression in adolescents, and can also be used in conjunction with other tests. However, the BDI by itself is inadequate to establish a diagnosis of depression. PMID- 1933747 TI - Adolescent and pre-adolescent suicide in Newfoundland and Labrador. AB - This study investigated suicides by people aged ten to 19 in Newfoundland and Labrador from 1977 to 1988. It is the first study of suicide in the province to use the records of death from all eight hospital pathology departments in the province and from the office of the Chief Forensic Pathologist. Cases were selected for the study using standardized criteria, independent of the manner of death recorded on the death certificate. A suicide rate of 4.37 per 100,000 was found. This rate and the age- and sex-specific suicide rates are lower than the official figures for Canada but higher than those reported in earlier Newfoundland studies. The rate for males was nearly five times the female rate, and the rate for people aged 15 to 19 was nearly six times that of people aged ten to 14. Suicide rates for Labrador were higher than for the island portion of the province for both Native and for non Native adolescents. Extremely high rates of suicide were found only among the Native population living in Northern Labrador, while none were recorded for Native people elsewhere. Firearms accounted for 54% and hanging for 33% of all suicides. Thirty percent of suicides occurred on a Saturday. Only 36 of the 63 deaths included in this study were designated as suicide on death certificates. The higher rate of under-reporting of suicide than in other jurisdictions suggests that official rates may not be useful for comparisons. The reasons for the high rate of under-reporting are discussed. PMID- 1933748 TI - Children, families and the cycle of disadvantage. AB - It is possible to reduce rates of school dropout, teenage pregnancy, arrests for violent crime, and long term dependence on welfare. Programs that have improved outcomes among children in disadvantaged families provide access to an array of services cross professional and bureaucratic boundaries, emphasize relationships of trust and respect, are deeply rooted in the community, are family focused, and recognize the distinctive needs of those most at risk. If health, mental health, social service and education programs with these attributes are to reach the large numbers who need them, the systems within which these programs operate must be restructured. PMID- 1933749 TI - The infant psychiatrist and the transplant team. AB - This case presentation delineates one possible role the infant psychiatrist can play in the care of infants suffering from severe medical illnesses who are hospitalized for long periods. It describes the process of liaison with many professional groups who treat such children, highlights some of the difficulties inherent in this work and provides some possible answers to such problems. PMID- 1933750 TI - Guilt loops. AB - Overlooking the role of parental guilt in recurrent parent-child conflict may limit effective interventions in family therapy. This paper presents a conceptual model of the role of parental guilt in the maintenance of recurrent dysfunctional sequences of parent-child conflict. The cybernetic model of guilt loops provides a framework for understanding and intervening in recurrent escalating parent child conflict which is characterized by ambiguous, inconsistent limit-setting and consequences. Interventions based on guilt loops address the interaction between parental guilt and dysfunctional behavior sequences and broaden the scope of possible interventions for the therapist. A clinical example illustrates the use of this model. PMID- 1933751 TI - Minors' right to psychiatric treatment. AB - This article provides a selected overview of the rights of minors under the Mental Health Act (Ministry of Health) and the Child and Family Services Act (Ministry of Community and Social Services) in the province of Ontario. Although the paper addresses specific issues related to mental health regulations as they apply to children and adolescents in Ontario, similar arguments apply to the regulations in most provinces. Specifically the paper raises some legal and ethical questions regarding minors' right to treatment. It is suggested that the legislation may impede access to treatment in some instances. PMID- 1933752 TI - Psychiatric consultation with children in underserviced areas: lessons from experiences in northern Ontario. AB - There are only 350 child psychiatrists in Canada. It is therefore unrealistic to expect them to be able to provide sufficient direct treatment, even in small densely populated communities with abundant resources. Such expectations are even more unrealistic in underserviced, sparsely populated areas. A review of the literature on psychiatric consultation in underserviced areas is presented along with a description of the consultation process, taking advantage of the "multiplier effect." Some of the realities of mental health consultation in underserviced areas are discussed, stressing the importance of consultation as a way of professional life. Some guidelines for the psychiatric consultant are outlined which would enhance the "multiplier effect". It is maintained that the training of psychiatric residents should include a supervised experience consulting in underserviced areas. Finally, it is hoped that psychiatric training programs, funding bodies, hospitals, and agencies, will recognize the value of this use of psychiatric expertise. PMID- 1933753 TI - An unusual approach to psychotherapy. PMID- 1933754 TI - Mandatory treatment of bipolar illness? PMID- 1933755 TI - Adolescent residential treatment: a one to three year follow-up. AB - Considerable difficulties have been encountered in the residential treatment of adolescents with psychiatric disorders. Few of these programs have been successful. This study describes the long term effectiveness of a residential treatment program for disturbed adolescents. This program was particularly successful in returning severely disturbed adolescents to the community. None of the adolescents needed intensive residential treatment during the follow-up period. Three objective measures (Global Assessment Scale, Level of Functioning Scale, Adolescent Functioning Scale) were used at three specific times (admission, discharge and long term follow-up) to determine the level of psychosocial functioning of each adolescent. A significant improvement was found in the adolescents' level of functioning. These treatment gains were maintained at the time of long term follow-up (one to three years). PMID- 1933756 TI - Reliability, validity and utility of the Fitness Interview Test. AB - Psychiatrists are being asked more and more often by the courts to determine whether or not criminal defendants are fit to stand trial. However, the Criminal Code provides few statutory guidelines on what constitutes fitness to stand trial. Perhaps as a result of the lack of standards, psychiatrists have typically relied on traditional clinical assessment procedures in determining whether or not an individual is fit to stand trial. In an effort to improve the quality and consistency of forensic assessments, researchers have designed instruments to assess fitness to stand trial. In Canada, the Fitness Interview Test (FIT) was developed for this purpose. This study evaluated the FIT for its validity, reliability and utility in the assessment of fitness. The FIT was found to have excellent interrater reliability and scale homogeneity. In addition, it was able to discriminate between groups of defendants rates as being fit and or unfit to stand trial. The scale did not seem to be differentially sensitive to the diverse facets of fitness, which may be attributed to the format and content of the scale items. Caution is advised in the use of the FIT pending revision of the scale. PMID- 1933758 TI - Relapse prevention in manic depressive illness: important and unimportant factors. AB - Many factors play a role in the safe and effective prevention of relapses. These include: selection of patients; organization of treatment; choice of drug; dosage and treatment regimen; clinical and laboratory monitoring; information and instruction given to patients and relatives; and psychotherapeutic and social support. Some of these factors have received much attention in the past, although perhaps not always the most important ones. This paper, a brief refresher course, discusses the priorities and precautions which must be considered when treating patients with manic depressive illnesses. PMID- 1933757 TI - Homebound aged: the dilemma of psychiatric intervention. AB - This study reports the 12 month experience of a hospital-based, multidisciplinary psychogeriatric community team. The patients evaluated were unable to come to the hospital clinics because of a psychiatric and/or physical disability. The group included some patients rarely seen in psychiatric office practice and outpatient facilities, but who posed problems for their families and the community. Some required referral to a clinic, crisis management or emergency hospitalization. Others however, required only minimal intervention. A total of 151 patients (119 females and 32 males) whose average age was 78.2, were seen. Seventy percent were widowed, single, divorced or separated; 43% lived alone. The patients were grouped according to the method of intervention used: psychiatric and social intervention--55%; social and nursing intervention--28%; no follow-up--11% and; emergency hospitalization--6%. Seventeen patients were left "untreated". These patients usually had more adequate family or community support than was initially apparent. They were referred for a crisis which was resolved quickly. An attempt is made to explain our approach, and several case examples are given. PMID- 1933759 TI - Evaluation of the Modified Mini-Mental State Examination in a general psychiatric population. AB - Studies of clinical cognitive screening tests began in the 1960s, and ten instruments have been reported in the English literature. In this study, we have compared the widely used Mini-Mental State Examination developed by Folstein with a reportedly enhanced version, the Modified Mini-Mental State Examination devised by Teng, using a sample of 250 patients (inpatients, outpatients, emergency). We have come to the conclusion that the modifications brought about by Teng result in a minor improvement of the validity of the Mini-Mental State Examination in a psychiatric patients in a general hospital. PMID- 1933760 TI - Long term psychotherapy training in residency: influences on therapy and training. AB - The authors discuss the changing role of psychotherapy training and the impact of rotations on long term psychotherapy in psychiatric residency. A conceptual model for a long term psychotherapy program for residents is presented, and a case example illustrates the influence of changes in setting, supervisors and in the resident-therapist's way of thinking have on the process of psychotherapy. The educational value of long term patient contact and the opportunity to use apparent obstacles in residency training as catalysts for growth and the opportunity to learn about psychotherapy are emphasized. PMID- 1933761 TI - The incidence and significance of perceptual qualities in the reported dreams of patients with anorexia nervosa. AB - The dreams of anorexic patients' were recorded using a standardized sleep questionnaire concerning the perceptual qualities and affects remembered from their dreams. The anorexic subjects consistently had less frequent dream recall, fewer dreams in colour and fewer pleasurable themes than was noted in the normal controls. Anorexics frequently saw themselves in their dreams as having a distorted body (especially an enlarged belly), a younger appearance, and experienced food and hunger dysphoria. The evaluation of an anorexic patient's dreams and their subsequent changes in both sensations and the frequency of reported dreaming may have diagnostic and as well as prognostic importance for the therapeutic assessment of anorexia nervosa. PMID- 1933762 TI - Intravenous clomipramine and obsessive-compulsive disorder. AB - A 62 year old woman presented with a long history of obsessive-compulsive disorder, the symptoms of which were not adequately controlled by oral clomipramine. The patient was started on intravenous clomipramine. Drug levels of both clomipramine and its active metabolite desmethylclomipramine were measured. Symptoms were controlled during her hospital stay. A three year follow-up report indicated the patient is doing well with no evidence of obsessive-compulsive or depressive symptoms. A discussion of the blood levels obtained and the caution to be exercised during intravenous administration is presented. PMID- 1933763 TI - Haloperidol-induced bronchospasm. AB - A case of haloperidol-induced bronchospasm is described, and possible etiologies are suggested. Since haloperidol is commonly used in the treatment of psychoses, it is important for clinicians to be aware of this potentially lethal yet treatable side-effect. PMID- 1933764 TI - Severe paternal sexual abuse in early childhood and systematic aggression against the family and the institution. AB - This report examines incest and its sequela in individuals suffering from severe chronic mental illness. Descriptive data drawn from 11 cases paints a clinical picture characterized by severe chronic psychotic symptoms and aggressive behaviour that are often precipitated by the family's rejection. In all patients, the incest for occurred over a long period of time, was violent, and was perpetrated by the male parental figure. Health care professionals need to increase their knowledge of and skills in the identification and treatment of sexual abuse. PMID- 1933766 TI - The role of the psychiatrist in dangerous offender hearings. AB - The current Canadian legislation regarding dangerous offenders is reviewed, with specific emphasis on the role of the required psychiatric testimony. It is suggested that, although this legislation as it is currently formulated could be viewed as an attempt to broaden the insanity defence, and permit the diversion of mentally ill offenders from a punitive to a therapeutic milieu, it enables the preventive detention of recidivist offenders. Some fundamental ethical issues which follow from this are identified, together with the issues which have dominated expert testimony in hearings held in British Columbia during the past 13 years. PMID- 1933767 TI - Akathisia, porphyria and low iron. PMID- 1933768 TI - Training residents in human sexuality. PMID- 1933765 TI - Psychogenic catatonia with elevated creatine kinase and autonomic hyperactivity. AB - A case is presented in which a young man with no psychiatric history and no previous exposure to psychotropic medication rapidly developed severe catatonia and autonomic hyperactivity, and an elevated creatine kinase level. He was treated with electroconvulsive therapy and recovered completely. This case suggests that a subgroup of patients who presented with symptoms resembling those of neuroleptic malignant syndrome and who have been treated with neuroleptics may suffer from severe psychogenic catatonia. PMID- 1933769 TI - Law, psychiatry and the survival of patients in the community. PMID- 1933770 TI - Does histologic grade in soft tissue sarcoma influence response rate to systemic chemotherapy? AB - To assess whether chemosensitivity in metastatic soft tissue sarcoma (STS) is influenced by the histologic grade of the tumor, the authors retrospectively analyzed tumor responses to doxorubicin-based chemotherapy in four prospective studies conducted at the Mayo Clinic, Rochester, Minnesota, between 1976 and 1984. A total of 131 patients with metastatic STS were included in these trials. All pathologic material was reviewed by one pathologist (H.M.R.) and graded according to the four-tier grading system of Broders. One hundred and sixteen patients were accepted for analysis. Objective regression rates according to grade were as follows: Grade 4, 55% (22 of 40 patients); Grade 3, 23% (7 of 31 patients); Grade 2, 19% (5 of 27 patients); and Grade 1, 0% (0 of 3 patients). Fifteen nongradable sarcomas were analyzed separately (27% [4 of 15]). In contrast to several reports suggesting that grade does not effect response, the authors found differences in response rates to be statistically significant for Grade 2 versus Grade 4 (P = 0.003) and Grade 3 versus Grade 4 (P = 0.006), but not for Grade 2 versus Grade 3 (P = 0.7). Additional comparisons adjusted for the histologic type of STS, chemotherapeutic regimen, performance status, age, and prior treatment confirmed these results. These results suggested that, in addition to being an important prognostic factor for survival in newly diagnosed STS, histologic grade may correlate with the probability of response and should be considered a stratification factor in future studies. PMID- 1933771 TI - Continuous infusion 5-fluorouracil with escalating doses of intermittent cisplatin and etoposide. A phase I study. AB - Continuous infusion 5-fluorouracil (CI 5-FU) and the combination of cisplatin (CDDP) plus etoposide (VP-16) have emerged as salvage regimens for metastatic breast carcinoma (MBC). In this study, 18 patients (15 with MBC) were entered into a Phase I study to determine the maximum intermittent doses of CDDP and VP 16 that could be added to 200 mg/m2/d CI 5-FU. The maximum tolerated dose of the combination was 40 mg/m2 of CDDP and 60 mg/m2 of VP-16 weekly for the first 8 weeks and every other week thereafter. The dose-limiting toxicities of the regimen were myelosuppression and thrombocytopenia. Two complete responses (both patients had received no previous chemotherapy) and one partial response were noticed. This regimen at the doses described here is appropriate for Phase II trials as an alternative to doxorubicin-based regimens for MBC. PMID- 1933772 TI - Characterization of cytochrome P450-dependent dimethylhydrazine metabolism in human colon microsomes. AB - Polyclonal antibodies to components of the rat liver cytochrome P450 system were used to examine the composition and function of the microsomal cytochrome P450 dependent monooxygenase system of human colonic mucosal cells. Anticytochrome P450 reductase antibody gave a strong band of immunocross-reactivity in human colon microsomes at the same molecular weight level as purified cytochrome P450 reductase from rat liver, as well as hepatic microsomes isolated from untreated or phenobarbital-treated rats. These results demonstrate the presence of cytochrome P450 reductase in human colon cells. Similarly, cytochromes P450 IIB1 and IIA1 also appear to be present in Western blots of human colon microsomes. These antibodies, as well as antibodies to reductase and cytochrome b5, inhibit dimethylhydrazine metabolism in human colon microsomes to varying degrees. These data argue for a functional P450-dependent drug metabolism system in colon capable of activating/metabolizing the colon-specific model carcinogen, 1,2 dimethylhydrazine. PMID- 1933773 TI - The influence of local control on metastatic dissemination of prostate cancer treated by external beam megavoltage radiation therapy. AB - The influence of local control on metastatic dissemination was analyzed in 601 patients with clinically staged A2 to C prostate cancer treated by high-energy external beam radiation therapy who did not undergo hormonal manipulation before disease progression. Median follow-up for surviving patients was 7.7 years. Ninety-three patients had locally recurrent disease. The actuarial incidence of metastases in these patients (70% at 13 years) was significantly higher than in the 508 patients without local failure (40% at 13 years, P less than 0.001). High stage, high grade, prior transurethral resection, elevated acid phosphatase, disease fixation to the pelvic sidewall, and failure to perform a baseline bone scan correlated positively with the occurrence of metastases. However, except for a slight excess of Stage C, none of the metastatic predictors were more common in patients who failed locally than in those who did not. The Stage C preponderance does not account for the difference in incidence of metastases between the two groups, in as much as metastases were significantly more common in Stage C when disease recurred locally than when it did not. Thus, local control of prostate cancer does decrease the likelihood of metastatic disease. Moreover, patients with local control experienced a significantly better disease-specific survival than patients who failed locally. PMID- 1933774 TI - Potential of human lymph node cells for antitumor activity mediated by interferon gamma. AB - The soluble antitumor activity of regional lymph node cells obtained from patients with cervical cancer was investigated by using a human tumor clonogenic assay (HTCA). A significant antiproliferative activity of the lymph node cells (LNCs) against a cervical cancer cell line, HeLa cells, was demonstrated by stimulation with either phytohemagglutinin (PHA) or concanavalin A (Con A), but not with interleukin-2 (IL-2). This antiproliferative activity of LNC was found in nonadherent cells, possibly T-cells. By using neutralizing antibody experiments, this activity was found to be attributed to interferon gamma (IFN gamma), but not to tumor necrosis factor (TNF), although both cytokines were produced from LNC. These results indicate that human LNC was able to exert an antiproliferative activity mediated through the cytokines by appropriate stimulation. PMID- 1933775 TI - Thyroid dysfunction associated with immunotherapy for patients with cancer. AB - The authors performed a prospective study to evaluate thyroid dysfunction in 130 patients with cancer who were receiving interleukin-2 (IL-2)-based immunotherapy. Primary hypothyroidism was the most common abnormality, occurring in 12% of patients before, 38% during, and 23% after immunotherapy. Hyperthyroidism occurred in 1%, 4%, and 7% of patients at those time intervals. Among patients initially euthyroid (n = 111), primary hypothyroidism developed in 32% during and 14% after immunotherapy, persisting a median of 54 days. Three patients required levothyroxine. Hyperthyroidism developed in 2% of patients during immunotherapy and 6% after. Thyroid dysfunction was not a function of sex, diagnosis, type of treatment, or response to immunotherapy. Elevated titers of antithyroglobulin and antithyroid microsomal antibodies were detected after treatment in 9% and 7%, respectively, of all patients without prior antibody abnormalities and did not correlate with response to therapy. The high incidence of therapy-induced thyroid dysfunction suggests that thyroid function should be carefully monitored in all patients receiving IL-2-based immunotherapy. PMID- 1933776 TI - Tumor-infiltrating lymphoreticular cells. Histologic and immunohistologic investigations performed on metastasizing squamous cell carcinomas of the head and neck. AB - Ten squamous cell carcinomas of the head and neck region and metastatic deposits in 41 cervical lymph nodes were investigated histologically and immunohistologically to determine the cellular immune response to the tumors, particularly the localization and phenotype of the tumor-infiltrating lymphoreticular cells. The lymphoreticular cells were accumulated preferentially in the stroma in and around the tumor. The foci of neoplastic cells usually contained smaller numbers of lymphoreticular cells. Lymphocytes and macrophages that lay in close contact with malignant cells did not exert histologically apparent signs of toxic effects on these cells. Macrophages (Ki-M6+) nearly always constituted the largest fraction of the lymphoreticular cells, but T lymphocytes (Leu-1+), T4-cells (Leu-3a+), and plasma cells were also often observed in large numbers. T8-lymphocytes (Leu-2a+) and T-accessory cells (Leu 6+) most often occurred in moderate numbers. Leu-6+ cells represented the only cell type found predominantly in the atypical epithelial complexes. All other cells investigated, i.e., B-lymphocytes (To15+), B-accessory cells (Ki-M4+), natural killer cells (Leu-7+), eosinophils, and tissue mast cells were usually encountered only in very small numbers of were virtually absent from the lymphoreticular infiltrates. A comparison of the cellular reaction in the primary tumors and their corresponding cervical lymph node metastases revealed differences for T8-lymphocytes, T4-cells, and T-accessory cells. Although T8 lymphocytes were more numerous in both the stroma and tumor foci of the metastases than in the primary tumors, T4-cells and T-accessory cells were present in greater numbers only in the tumor foci of the metastases. The preferential localization of tumor-infiltrating lymphoreticular cells in the tumor stroma and the absence of a visible cytotoxic effect of lymphocytes and macrophages in direct contact with tumor cells support the hypothesis of a deficient immune response to clinically detectable squamous cell carcinomas of the head and neck region. PMID- 1933777 TI - Intratumoral heterogeneity in DNA ploidy of esophageal squamous cell carcinomas. AB - Intratumoral heterogeneity in DNA ploidy was investigated in 23 cases of squamous cell carcinoma of the esophagus. Nuclear DNA content was determined for multiple samples taken from the same tumor, using a flow cytometric technique. The incidence of DNA aneuploidy was 87% in this series, and DNA indices ranged from 0.78 to 2.64 but most of them fell within values between 1 and 2. Of these cases ten (43.5%) showed intratumoral heterogeneity in DNA ploidy; in addition to a diploid population, one to four heterogeneous aneuploid subpopulations were discernible in the same tumor. However, morphologic variation was minimal within the same tumor. DNA index seen in metastatic lesions was identical with one of those in the primary lesion. Mechanisms responsible for intratumoral difference in DNA ploidy are also discussed from the aspect of tumor progression. PMID- 1933778 TI - Stimulatory effects of growth hormone on rat bladder carcinogenesis. AB - The authors investigated the influences of recombinant human growth hormone (rh GH) on rat urinary bladder carcinogenesis induced with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Rats belonging to the control group (Group I, n = 19) were given 0.05% BBN in drinking water for 9 weeks, and the bladder was excised on the 22nd week after the initiation of BBN administration and inspected. All animals developed visible tumors in the bladder. The mean number of tumors per bladder was 11.26 +/- 5.21, and the mean total volume of tumors per bladder was 126.1 +/- 212.7 microliters. In all but one of the experimental groups (Group V) and in the control group, all animals developed visible tumors in the bladder. When 0.5 units of rh-GH was injected subcutaneously once a week from the week 1 through the week 6 (Group II; n = 20), the mean number of tumors and mean total volume of the tumors were 12.15 +/- 6.59 and 206.6 +/- 318.0 microliters, respectively. When the administration period of rh-GH was changed to between week 7 through the week 12 (Group III; n = 19), the mean number of tumors and mean total volume of the tumors were 16.95 +/- 7.07 and 204.5 +/- 317.7 microliters, respectively. When rh-GH was administered from the week 13 through the week 18 (Group IV; n = 19), the respective values were 16.79 +/- 10.75 and 213.4 +/- 274.6 microliters. In Group V (n = 19), which received only rh-GH from week 1 through the week 6, no tumors were detected. There were statistically significant differences in the mean tumor numbers between Groups I and III, Groups I and IV, and Groups II and III. The mean volume of individual tumor was the greatest in Group II, although the differences were not statistically significant in comparison with the other groups. Histologically, all tumors were transitional cell carcinoma in every group. There were no statistically significant differences in distributions of tumor stage and tumor grade between any groups. These findings suggest that rh-GH enhances the promotion of carcinogenesis of chemically induced rat urinary bladder cancer. It will be necessary to elucidate whether this effect of rh-GH is expressed by the somatostatin hypothesis of GH action, its direct action, or some other mechanisms. PMID- 1933779 TI - Molecular studies of chronic myelogenous leukemia using the polymerase chain reaction. AB - Thirty-two cases of chronic myelogenous leukemia (CML) were studied to determine whether there was a correlation between the position of the chromosome breakpoint within the breakpoint cluster region (bcr) on chromosome 22 and the type of chimeric mRNA expression. One case with the chromosome breakpoint in zone 2 of the major bcr (Mbcr) and six cases with breakpoints in zone 3 expressed Mbcr exon 2-abl (b2-a) mRNA, and they were in distinguishable at the level of mRNA expression. The remaining ten cases with breakpoints in zone 3 and all ten cases with breakpoints in zone 4 expressed Mbcr exon 3-abl (b3-a) mRNA with or without b2-a mRNA. Three cases with breakpoints in zone 5 expressed b3-a mRNA, and none of these expressed Mbcr exon 4-abl(b4-a) mRNA. The cases with breakpoints in zones 4 or 5 had b3-a mRNA expression indistinguishable from those with breakpoints in zone 3. In two patients, the breakpoint in the bcr could not be determined by Southern hybridization using the 3' bcr probe or the large bcr probe. However, when analyzed for chimeric mRNA expression, both of them exhibited b3-a chimeric mRNA, suggesting the possibility that the entire Mbcr is deleted in the majority of leukemic cells in these patients. These studies indicate that Southern hybridization analysis combined with the polymerase chain reaction assay is a useful approach to understanding the pathologic role of bcr abl gene recombination and expression in the development of CML. PMID- 1933780 TI - Malignant epithelial tumors in the minor salivary glands, the submandibular gland, and the sublingual gland. Prognostic factors and treatment results. AB - Ninety-five malignant tumors in the submandibular gland, the sublingual gland, and the minor salivary glands seen in a 25-year period were reviewed. The patients were retrospectively staged using the Union Internationale Contre le Cancer (UICC) classification. The most frequent tumor was adenoid cystic carcinoma, followed by adenocarcinoma. The submandibular gland was the most frequent location. Five-year and 10-year crude survival rates were 62% and 43%, respectively. Clinical stage was the most important prognostic factor. Survival was not correlated with location of tumor, although recurrence and metastases occurred more frequently in patients with cancer of the submandibular gland. Histologically, the 5-year and 10-year survival was significantly better for patients with adenoid cystic carcinoma compared with the other types; however, although still significant, this difference diminished at 10 years, confirming the need for a long observation time for patients with this tumor. PMID- 1933781 TI - Tumor-associated glycoprotein-72 serum levels complement carcinoembryonic antigen levels in monitoring patients with gastrointestinal carcinoma. A longitudinal study. AB - Eighty-two patients diagnosed with gastrointestinal (GI) adenocarcinoma were evaluated before and for 26 months after primary tumor resection for the presence of two serum tumor markers: tumor-associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA). Elevated TAG-72 and CEA serum levels were found preoperatively in 32 (39%) and 34 (41.5%) of the 82 patients, respectively. The percentage of patients with elevated serum levels of either TAG-72 or CEA was 56.1% (46 of 82). Twelve (15%) patients who had normal CEA serum levels had elevated TAG-72 serum levels, and conversely, serum from 14 (17%) patients who were TAG-72 negative were CEA positive. Forty-five of the 82 patients were diagnosed with advanced disease (i.e., Stages C and D for colorectal, Stages III and IV for stomach), and 29 (64.4%) and 26 (57.8%) of those patients had elevated serum levels of TAG-72 or CEA, respectively. Elevated levels of either TAG-72 or CEA, however, were found in sera of 82.2% of patients with advanced GI cancer, which is an increase of 24.4% over the use of CEA antigen alone as a marker of disease. The measurement of both TAG-72 and CEA may improve the diagnosis of patients with GI malignant disease due to the apparent complementary association which exists between these tumor markers. Serum TAG-72 and CEA levels were monitored in 31 patients for varying lengths of time after resection of the carcinoma; 11 patients developed recurrent disease. Sera from nine of 11 (81.8%) of these patients had elevated TAG-72 levels and six of 11 (54.5%) had elevated CEA levels. Tumor marker elevations were observed either before (35 to 166 days) or at the time of diagnosis of recurrence. The elevation of one or both markers correlated with the clinical status in ten of 11 (90.9%) patients with recurrence. In addition, 20 patients who were clinically free of disease after more than 700 days' follow-up had normal serum levels of both TAG-72 and CEA. These findings suggest that the combined use of serum TAG-72 and CEA measurements may improve detection of recurrence in patients with GI cancer and may be useful in the postsurgical management of GI adenocarcinoma patients. PMID- 1933782 TI - Rectal cell proliferation and colorectal cancer risk level in patients with nonfamilial adenomatous polyps of the large bowel. AB - The authors evaluated cell kinetics of apparently normal rectal mucosa in the following subjects: 25 with single small adenoma (smaller than 10 mm) of the large bowel, 12 with multiple small adenomas, 28 with a single large adenoma (larger than 10 mm), 22 bearing multiple adenomas among which at least one was larger than 10 mm, 32 with cancer of the large intestine, and 32 controls without colorectal diseases. The study was performed by means of incubation of biopsy specimens with tritiated thymidine and autoradiography. The labeling index was similar in all of the groups. However, patients with one or more large adenomas showed a shift of the proliferative compartment toward the top of the crypts similar to that observed in patients with cancer. This abnormal proliferative pattern was not noticed in patients with one or more small adenomas and was not related to the number of adenomas of each subject. The presence of defects of cell growth in the normal rectal mucosa of patients with large adenomas may indicate that subjects with this abnormality are at high risk of adenoma growth and progression to cancer. PMID- 1933783 TI - Simultaneous carcinoma involving the endometrium and the ovary. A clinicopathologic, immunohistochemical, and DNA flow cytometric study of 18 cases. AB - Eighteen carcinomas involving both the endometrium and the ovary were studied. Stage, size, bilaterality and pattern of ovarian involvement, histologic types and grades, presence of endometrial hyperplasia or ovarian endometriosis, myometrial, tubal, lymphatic and blood vessel invasion, and follow-up of the patients were all evaluated. Accordingly, the cases were classified as follows: Group A (nine cases), two separate primary tumors; and Group B (nine cases), uterine primaries with ovarian metastasis or ovarian primaries with uterine metastasis. Immunohistochemical stains (CAM 5.2, wide-spectrum keratin, vimentin, carcinoembryonic antigen (CEA), CA 12.5, CA 19.9) were performed in all cases. Flow cytometric determination of nuclear DNA was done in 13 (seven Group A and six Group B tumors). Of the nine cases with independent primary tumors, seven showed different immunohistochemical profiles in the ovarian and uterine tumors, whereas only four of the nine metastatic ones had similar staining characteristics. Five cases with independent primary tumors, but only one of the metastatic group, exhibited different aneuploid stemlines in the endometrial and ovarian tumors. The other seven (two independent and five metastatic) cases had similar DNA indexes in both tumors. Immunohistochemical and DNA flow cytometric study may be of some value for the distinction between metastatic and independent tumors, but differential diagnosis must presently rely largely upon conventional clinicopathologic criteria. PMID- 1933784 TI - Human immunodeficiency virus-related lymphoma. Prognostic factors predictive of survival. AB - In an attempt to determine factors predictive of survival in patients seropositive for human immunodeficiency virus (HIV) with acquired immune deficiency syndrome (AIDS)-related lymphoma, the authors studied 60 such patients, all of whom were treated with curative intent. Eleven patients presented with lymphoma primary to the brain (P-CNS); the remaining 49 had systemic AIDS-related lymphoma. Patients with P-CNS lymphoma had more severe underlying HIV-related disease than did patients with systemic lymphoma as evidenced by a higher incidence of AIDS before the diagnosis of lymphoma (73% versus 37%; P = 0.04), and lower median number of CD-4-positive lymphocytes in peripheral blood at diagnosis of lymphoma (30/dl versus 189/dl; P = 0.005). Median survival of such patients was 2.5 months versus 6.0 months for patients with systemic lymphoma (P = 0.04). Forty patients with systemic AIDS-related lymphoma have died; three factors were strongly associated with shorter survival: (1) Karnofsky performance status (KPS) of less than 70% (multivariate relative survival risk [RSR] = 3.1); (2) history of AIDS before the diagnosis of lymphoma (multivariate RSR = 3.0 for opportunistic infection plus Kaposi's sarcoma); and (3) bone marrow involvement (RSR = 3.1)). All three factors (KPS of less than 70%, prior AIDS diagnosis, and marrow involvement) were associated with early demise attributed to AIDS, whereas death attributed to lymphoma per se was associated with only two factors (KPS of less than 70% and marrow involvement). In the absence of all three risk factors, a "good prognosis" group of 17 patients was defined, with a median survival of 11.3 months; the median survival of the remaining patients ("poor prognosis") was 4.0 months (P = 0.0002). Attainment of complete response to therapy (CR) was strongly related to prolonged survival in the patients in the good prognosis group (17.8 months in patients with CR versus 5.0 months in those with less than CR); however, such meaningful prolongation of survival was not seen in patients with poor prognosis who attained CR (6.3 months versus 3.4 months). The patients with poor prognosis may be unable to tolerate the insult of multiagent chemotherapy, experiencing low CR rates (25%) and death caused by lymphoma and AIDS. However, patients in either prognostic category who attained CR remained at risk for dying of AIDS while the lymphoma was in remission. Thus, it is apparent that meaningful prolongation of survival in the patient with AIDS-related lymphoma will require not only effective antineoplastic intervention, but also control of the underlying HIV infection. In addition, future therapeutic trials should stratify patients based upon the prognostic factors defined here in an attempt to clarify the results obtained. PMID- 1933786 TI - Age as a prognostic factor in patients with squamous cell carcinoma of the uterine cervix. AB - Correlations between age and several prognostic factors, such as histologic cell type, depth of invasion, intravascular invasion, and lymph node metastases (LNM), were analyzed in squamous cell carcinoma of the cervix (SCC). A total of 380 patients with Stage IB or more advanced SCC underwent radical hysterectomy at the authors' institution from 1971 to 1987. The cases were divided into four age groups: 30 to 39 years, 40 to 49 years, 50 to 59 years, and 60 to 69 years. The depth of invasion was classified in four categories according to pathologic examination of surgical specimens. The only significant factor was the frequency of LNM with deeper invasion, which was less in the 60-to-69-year age group than in the younger age groups. The 5-year survival rates of the patients with LNM also were higher in the 60-to-69-year group. Thus, age 60 or older can be considered a prognostic factor correlating to LNM in squamous cell carcinoma of the cervix. PMID- 1933785 TI - Gallium-67 scans as an adjunct to computed tomography scans for the assessment of a residual mediastinal mass in pediatric patients with Hodgkin's disease. A Pediatric Oncology Group study. AB - This study determines the utility of gallium-67 (Ga-67) scintigraphs as an adjunct to computed tomography (CT) scans for the assessment of residual mediastinal masses in children and adolescents with advanced-stage Hodgkin's disease. At diagnosis 42 patients with CT scan-documented mediastinal disease had a Ga-67 scan performed. Thirty-four of 42 patients (81%) had gallium-avid mediastinal lesions, whereas in eight (19%), the Ga-67 scan was negative. At the completion of eight cycles of therapy of Mustargen (mechlorethamine), Oncovin (vincristine), procarbazine, prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), 21 of 34 patients with initially positive Ga-67 scans had them repeated; 18 of 21 converted to negative results, and three remained positive. In 11 of 18 patients, the loss of gallium avidity was consistent with a negative mediastinal CT scan. In seven, although the gallium scan was negative, the CT scan remained positive; all seven patients had a mediastinal biopsy of suspected residual disease and in all seven the biopsy results were negative for Hodgkin's disease. These preliminary results in a small cohort of patients demonstrate that Ga-67 scans may be of benefit in evaluating residual mediastinal masses in patients with Hodgkin's disease. PMID- 1933787 TI - Association of increased body mass index with diminished tumor estrogen receptor (ER) level in breast cancer patients younger than 50 years of age with ER positive tumors. PMID- 1933788 TI - Plasma cell granuloma in the nasal cavity. PMID- 1933789 TI - Pregnancy-associated cancer. PMID- 1933790 TI - Diffuse bony metastases. PMID- 1933791 TI - Cancer control and the older person. An overview. AB - Cancer is essentially a disease of older persons, yet the efforts made toward prevention and detection in this age group are seldom as energetic as those expended on younger individuals. It is apparent that age in itself is not a reason for benign neglect of neoplastic disease in older persons. The underlying factors that affect the behavior of cancer in older patients require intensive study. Comprehensive cancer prevention and detection services are economically sound in this age group. PMID- 1933792 TI - Gerontology as oncology. Research on aging as the key to the understanding of cancer. AB - It is widely appreciated that age is a powerful risk factor for cancer. This review considers two possible explanations for the exponential increase in most neoplasms in the elderly, arguing in favor of the idea that tumor progression proceeds at faster rates in older mice and older persons than in younger mice and younger persons. Three processes that alter the rate of aging, i.e., speciation, food restriction, and selective breeding, have parallel effects on cancer incidence. This suggests that the two processes are intimately connected. Elucidation of the mechanism(s) by which the aging process controls the rate of tumor development deserves high priority in experimental oncology. One such possible mechanism, the age-associated decline in immunologic defenses, is discussed at length in an attempt to rehabilitate the idea that a loss of immune function may contribute to the vulnerability of the elderly to cancer. PMID- 1933793 TI - Cancer in the aged. An epidemiologic perspective on treatment issues. AB - Persons 65 years of age and older bear the greatest burden of cancer; 55% of all malignancies occur in this age group. Sixty-seven percent of all cancer deaths occurred in this population in 1988. This article describes the magnitude of the cancer problem for this age group according to major cancers (colon, rectum, lung/bronchus, pancreas, stomach, urinary bladder, breast, and prostate). Data are cast against the demographics of aging in the United States. These facts emphasize an urgent need to concentrate more attention on problems unique to the elderly for early detection, diagnosis, and treatment. Information gaps are also identified. PMID- 1933794 TI - Psychosocial issues. Psychological and social issues for older people with cancer. AB - Elderly people vary from one another and from earlier generations, making generalizations about psychosocial issues for older patients with cancer risky. Social issues for older people with cancer include multiple losses, the reactions of others, arranging for their own care, and meeting responsibilities for others. Older persons with cancer may be primary family caregivers for other relatives. Psychological issues include learned helplessness and loss of control. Routine assessment of psychological and social factors, including patients' preferences, should be done through direct queries to patients. A detailed psychosocial research agenda is proposed. When possible, psychosocial studies should be linked to studies of the disease and its treatment. PMID- 1933795 TI - Targeting health advocacy efforts toward the older population. AB - Three American Association of Retired Persons health education programs addressing the prevention, detection, and treatment of cancer illustrate successful strategies for mobilizing older adults to be advocates for their own health. Programs include a national initiative to decrease smoking among adults older than 50 years of age, community education efforts to increase mammography use among older women, and peer education workshops designed to teach older patients consumer skills that will enable them to make informed treatment decisions. PMID- 1933796 TI - Biology of cancer and aging. AB - The greatest risk factor for cancer is aging. Human cancer incidence increases exponentially with advancing age. Cancer growth rate and potential for metastatic spread may be influenced by age-specific change in host response. Because cancer and aging are, thus, inextricably linked, the American Cancer Society should encourage submission of research proposals that address the mechanisms of aging and how aging alters cancer development. PMID- 1933797 TI - Cancer control and the older person. Issues in treatment. AB - The Committee on Treatment acknowledged the paucity of information related to the management of cancer in older patients and identified short-term and long-term efforts to study these issues. Short-term efforts should focus on effects of cancer and cancer treatment on survival and quality of life, efficacy and toxicity of antineoplastic therapy, barriers to adequate treatment, alternative settings of cancer care, and special supportive care needs. Long-term efforts should focus on unique features of cancer in older patients, long-term effects of cancer and cancer treatment, and prevention and detection of new primary malignancies. The Committee recognized that our recent advances in cancer treatment including palliative surgery, limited surgery, radiosurgery, and antidotes to drug toxicity may improve the tolerance of antineoplastic therapy by older patients and be beneficial in terms of survival and quality of life. PMID- 1933798 TI - Cancer control and the older person. Prevention and detection in older persons. AB - Older persons are appropriate targets for a range of prevention and early detection interventions, however, greater emphasis should be given to structuring the delivery of prevention and detection services to the special needs of this population. This may require research and program development to reach older persons in the most effective and cost-effective manner. The American Cancer Society and other program efforts must accommodate the heterogeneity and special needs of segments of the older population. Racial and cultural minorities, impoverished persons, the cognitively impaired, and the physically impaired are four groups requiring special attention. Early detection guidelines specific to older persons should be developed. PMID- 1933799 TI - Cancer control and the older person. Psychosocial issues. AB - Three major areas related to psychosocial issues pertinent to the provision of cancer control services to older people have been delineated. These are values and medical decision making, psychosocial barriers to screening and access to care and services, and quality of life, including rehabilitation. These areas are explored, salient issues are defined, and specific questions and areas for consideration in future research are identified at the macro and micro levels. PMID- 1933800 TI - Advocacy. Necessary to achieve cancer control goals. AB - As resources become increasingly scarce, oncology professionals and consumers of oncology services are increasingly engaging in advocacy efforts to achieve goals in cancer control. Effective advocacy includes both legislative and direct educational efforts. PMID- 1933801 TI - A phase I clinical trial of didemnin B. AB - Didemnin B is a depsipeptide extracted from the marine tunicate Trididemnin cyanophorum. This agent is a potent inhibitor of L1210 growth in vitro and has activity against murine B16 melanoma, P388 leukemia, and M5076 sarcoma in vivo. The results of preclinical toxicologic tests demonstrated abnormalities in clotting parameters thought to be secondary to drug-induced liver dysfunction. Thirty-five patients with advanced cancer received didemnin B according to a 5 day bolus schedule with dose levels ranging from 0.03 to 2.00 mg/m2/d. The dose limiting toxicity was nausea and vomiting. Sporadic elevation of the hepatic enzyme level occurred but was not dose limiting. Two patients had anaphylactic symptoms possibly related to the 5% polyoxyethylated castor oil (Cremophor EL, BASF, Ludwigshafen, Germany) vehicle during the drug infusion. Clinical bleeding was not observed and myelosuppression was not significant. No partial or complete tumor responses were seen. The recommended Phase II dose for the 5-day schedule is 1.6 mg/m2/d. PMID- 1933802 TI - Continuous infusion gallium nitrate for patients with advanced refractory urothelial tract tumors. AB - A Phase I-II trial of gallium nitrate was conducted in 40 patients with bidimensionally measurable urothelial tract tumors who had failed to respond to combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin. Partial responses were observed in 4 of 23 patients (17.4%) who received 350 mg/m2/d or more for 5 days by continuous intravenous infusion. In two additional patients who received 350 mg/m2/d or more, a minor response and a mixed response were observed. The median duration of response was 4 months (range, 2 to 8 months). A dose-response relationship was suggested because no responses were observed in 17 patients who received less than 350 mg/m2/d. Myelosuppression was minimal. The dose-limiting toxic reaction was a reversible optic neuropathy that occurred in 3 of 11 patients who received 400 mg/m2/d. Further evaluation of infusional gallium nitrate is warranted in patients with urothelial tract malignant tumors. PMID- 1933803 TI - Diagnosis of paraaortic and pelvic lymph node metastasis of gynecologic malignant tumors by ultrasound-guided percutaneous fine-needle aspiration biopsy. AB - Transabdominal ultrasonography was done in patients with gynecologic malignancies to detect paraaortic and pelvic lymphadenopathy. Of the 78 patients who underwent ultrasonic examination of pelvic lymph nodes, pelvic lymphadenopathy was detected in 24, of whom ultrasound-guided percutaneous fine-needle aspiration biopsies (FNAB) were done in 16. Of these 16 patients, the results of 13 biopsies were positive. Of the 41 patients who underwent ultrasonographic examination of the paraaortic lymph nodes, 27 had paraaortic lymphadenopathy. Ultrasound-guided percutaneous FNAB were done in 26 of these 27 patients, with positive findings in 21 of the 26. It was concluded that ultrasound-guided percutaneous FNAB is useful in detecting metastatic lymph nodes in gynecologic malignancies. PMID- 1933804 TI - Treatment of primary squamous cell carcinoma of the upper urinary tract. AB - Forty-six patients with primary squamous cell carcinoma of the upper urinary tract treated over a 44-year period were studied. The lack of characteristic presentation caused delay in diagnosis. Associated urinary calculi were found in only five (11%) of the patients. Almost all of the tumors were histologically high grade; at surgery, 84% of the tumors were locally advanced or metastatic. Prognosis is poor independent of treatment; the overall 24-month survival rate was 22%. Comparison with a previous study of renal pelvic transitional cell carcinoma indicates that these two forms of urothelial neoplasm are biologically different. PMID- 1933805 TI - Treatment of unknown primary melanoma. AB - Sixty-four patients with unknown primary melanoma were identified among 1045 new patients with melanoma (6%) seen during an 11-year period. Their mean age was 44.5 years (median age, 42.7 years). Of these, 39 (59%) were men, and 25 (38%) were women. In 34, only one site was involved. Common single sites were the axilla (29%), groin (24%), and neck (32%). Most of the melanomas (88%) were melanotic. Patients with localized melanoma surgically treated (n = 34) had a median survival of 53 months, and a 5-year survival rate of 45%. The respective rates for disseminated melanoma were 7 months and 10% (P = 0.00001). Localized, unknown primary melanoma should be treated with radical excision because a substantial proportion of patients so treated survive 5 years. PMID- 1933806 TI - Recombinant alpha-2b-interferon dynamic test as a potential tool in predicting disease status during second look in ovarian cancer. A preliminary report. AB - The circulating levels of a 90-kilodalton (KD) tumor-associated antigen were measured in the blood of 26 patients with ovarian cancer in clinical remission who received a short course of recombinant alpha-2b-interferon (rIFN-alpha-2b, 3 million U/m2/d intramuscularly for 3 days) before second-look procedures. The administration of rIFN-alpha-2b to 90-KD antigen-positive patients produced a slight increase of the marker. However, in patients without the marker but with evidence of disease, a remarkable increase above the cutoff level was observed. Less pronounced modifications of 90-KD antigen serum levels were found in patients with no disease at second look. Moreover, considering the 90-KD antigen mean percentage increase, the dynamic test with rIFN-alpha-2b was able to eliminate five of six false-negative results obtained with the 90-KD antigen basal assay alone. The sensitivity of the assay increased to 92% after IFN compared with 54% for the 90-KD antigen assay alone. An increase (greater than 100% above pretreatment titer) of 90-KD antigen levels during the test also was observed in four patients with no evidence of disease at second look. In two of these false-positive cases, recurrence of disease was observed 13 and 24 months later. At the time of this analysis, none of the patients with a negative second look and negative dynamic test had relapsed. These results suggest that the dynamic test with rIFN-alpha-2b might be a new tool to assess disease status in patients with ovarian cancer before second-look procedures. PMID- 1933807 TI - Expression of class I histocompatibility antigens in transitional cell carcinoma of the urinary bladder in relation to survival. AB - The expression of class I histocompatibility antigens (HLA) in transitional cell carcinoma of the bladder was studied by the immunoperoxidase technique and correlated with tumor differentiation and survival. Tumors of 33 patients who underwent cystectomy were examined; 57% of the tumors expressed HLA class I antigens. Positive expression was observed in 5 of 6 cases with Grade 1 tumors, 8 of 13 with Grade 2, and 6 of 14 with Grade 3. The 5-year survival was significantly better in patients with HLA class I-positive tumors (74%) compared with those with negative tumors (36%, P less than 0.05). The expression of HLA class I on tumor cells may serve as a target for the immune response and control the metastatic potential of the tumor. These results suggest that HLA class I expression in bladder carcinoma is a prognostic indicator that should be considered in treatment planning. PMID- 1933808 TI - Cellular expression of K-type pyruvate kinase in normal and neoplastic human tissues. AB - The cellular expression of K-type pyruvate kinase was studied immunohistochemically in several normal and neoplastic tissues of human origin. The authors used the monoclonal antibody, designated as ES1, which was raised against human K-type pyruvate kinase. In contrast to the normal counterparts, a strong immunoreactivity was found in a rhabdomyosarcoma (n = 1), in a carcinoma of the pancreas (n = 1), and in neurofibromas (n = 2). Furthermore, the staining in leiomyosarcomas (n = 2) was shown to be more intense when compared with both normal smooth muscle cells and leiomyomas (n = 2). These findings show that knowledge about the cellular expression of the K-type pyruvate kinase identifies cell types for which its expression serves as oncodevelopmental marker. In addition, these immunohistochemical studies give information whether shifts toward K-type containing isozymes of pyruvate kinase, which are determined by electrophoresis in whole cytosolic extracts of various tumors, are due to an altered gene expression or due to proliferation of cells which normally express already the K-type pyruvate kinase. The first possibility probably occurs in rhabdomyosarcomas. The latter possibility seems to be valid for astrocytomas because astrocytes express the K-type pyruvate kinase in normal brain. PMID- 1933809 TI - DNA ploidy is associated with growth potential in gastric carcinoma. AB - To correlate growth potential with DNA ploidy 109 patients with early gastric carcinoma and 132 patients with advanced gastric carcinoma were studied. Early gastric carcinomas were classified by growth potential into the small mucosal type, the superficially spreading (super) type, or the expansively penetrating (Pen A)/infiltratively penetrating (Pen B) types. Advanced gastric carcinomas were classified into funnel, column, or mountain types, each of which was divided further into expanding and infiltrative types. Cell nuclear DNA content was measured by microspectrophotometric study and classified as either low or high ploidy according to the degree of dispersion on the DNA histogram. Super type early and funnel type advanced carcinomas, characterized by superficially spreading growth, were more likely to have low DNA ploidy. In contrast, Pen A type early and column-expanding type advanced carcinomas, characterized by expansively penetrating growth, were more likely to have high DNA ploidy. PMID- 1933810 TI - The prognostic significance of ploidy analysis in operable breast cancer. AB - The nuclear DNA content of 98 operable breast cancers was determined by flow cytometric analysis using paraffin-embedded tissue. All patients were on follow up and failure of treatment or recurrences were identified. DNA ploidy data in the form of ploidy status and DNA index (DI) has been correlated with various clinical and histopathologic factors. The only significant correlation using univariate analysis exists between the histologic grade and DI (P less than 0.025), recurrence of the disease and ploidy status (P less than 0.005), and recurrence of the disease and DI (P less than 0.005). The absence of correlation of ploidy status with other tumor derived factors indicates the independent nature of ploidy as a prognostic factor. Multivariate analysis showed that in the whole-group ploidy (P less than 0.01), tumor margin (P less than 0.01), and menopausal status (P less than 0.01) were significant factors in the order mentioned. DI with a cut of at 1.29 is not found to be a significant factor in the multivariate analysis. The maximum prognostic value of ploidy status was observed in the postmenopausal group (P less than 0.0005). In the node-negative group ploidy status (P less than 0.05) is the only independent significant factor predicting for early relapse. It is concluded that ploidy status is an independent prognostic factor predicting for recurrence of the disease. In the node-negative subgroup this could be used to identify the subset of patients who may benefit from adjuvant treatment. PMID- 1933811 TI - Histopathologic findings of minute foci of squamous cell carcinoma in the human esophagus. AB - To examine the histogenesis and progression of esophageal squamous cell carcinoma, 76 cases of a primary squamous cell carcinoma were reviewed retrospectively, and 16 lesions of squamous cell carcinoma of the esophagus less than 1.0 cm in diameter were studied histopathologically. None of the patients had received radiation therapy preoperatively. Among 16 foci, 13 were intraepithelial carcinomas, and three were restricted to within the mucosa. In two patients with a solitary, minute cancer, there were no associated areas of dysplasia. In 11 patients with multiple primary minute foci, seven contained 14 areas of dysplasia in the esophagus. There was no continuity between the minute foci of carcinoma and areas of dysplasia. These findings are interpreted to mean that dysplasia is a "subcancerous" lesion rather than a "precancerous" one and that various degrees of lesions such as dysplasia and carcinoma occur multicentrically in the same esophagus. The sequence of dysplasia to carcinoma must be examined using the techniques of molecular biology. PMID- 1933812 TI - The incidence and significance of thromboembolic complications in patients with high-grade gliomas. AB - Coagulation system abnormalities in patients with malignancy ranges from asymptomatic laboratory abnormalities to overt clinical manifestations. To determine the incidence and significance of clinically manifest thromboembolic phenomena in patients with high-grade gliomas, the records were analyzed of 77 patients that presented between January 1985 and June 1988. Fifteen patients (19%) had clinically manifest deep venous thrombosis and/or pulmonary emboli during the course of their disease. All these patients were ambulatory before and at the time of diagnosis of the event. The thromboembolic episodes occurred at the time of initial management of the primary tumor while there was documented clinical improvement in the functional status of the patient or at the time of progression of the disease. One patient died as a result of a pulmonary embolism; in two others, an embolism was a significant contributor to the patient's death. Anticoagulation resulted in complications in two of eight patients treated. Thromboembolic events occur with high frequency in patients with high-grade gliomas and contribute to the high morbidity and mortality seen in these patients. The optimum approach to screening and the treatment of these events has not been determined. PMID- 1933813 TI - Hypercalcemia in patients with esophageal carcinoma. The pathophysiologic role of parathyroid hormone-related protein. AB - To elucidate the actual incidence of hypercalcemia in patients with esophageal carcinoma, 382 consecutive cases admitted to the National Cancer Center Hospital (Tokyo, Japan) from 1983 to 1988 were investigated. Hypercalcemia was detected in 5 patients of 376 (1.3%) at the time of primary detection of cancer, and in 45 patients of 120 (38%) patients with recurrent or unresectable cancer who were monitored within 2 months of death. These observations demonstrated that this electrolyte imbalance is a frequent paraneoplastic syndrome observed in patients with advanced esophageal carcinoma. With regard to the etiology, bone metastases were detected in 13 of 49 patients with hypercalcemia; the remaining 36 patients were assumed to be induced by the production of hypercalcemic substance(s) by tumor tissues. Parathyroid hormone-related protein (PTHrP) is a newly discovered factor which increases serum calcium in vivo. The detection of PTHrP mRNA in tumor tissues as well as the production of PTHrP-like immunoreactivity by tumor tissues were closely associated with the development of hypercalcemia, suggesting that PTHrP is the major cause of hypercalcemia in patients with esophageal carcinoma. PMID- 1933814 TI - Gene mapping in cancer. AB - Observation of genetic alterations that appear consistently in specific types and stages of cancer provides a strong impetus to cancer geneticists to focus their investigations on the exploration of such volatile regions of the human genome. Introduction of powerful molecular cytogenetic and molecular genetic methods in recent years permits more detailed analysis, which will help researchers in their efforts to determine if such areas of the human genome have a functional role in the initiation and progressive development of leukemias and solid tumors. This discussion will focus on several provocative molecular cytogenetic tools that are currently available to localize potential cancer-associated genes and on how these methods are being used in conjunction with the current modes of analysis, including cytogenetics and somatic cell genetics. In addition, we will explore how these methods will help to isolate and dissect recently discovered cancer associated genes within the human genome. All of these methods used in combination with each other will provide essential DNA markers for future diagnostic and prognostic evaluation of cancer. PMID- 1933815 TI - Involvement of chromosome 13 in myelodysplastic syndromes. AB - We report 2 of 80 cases of myelodysplastic syndromes (MDS) cytogenetically studied, with involvement of chromosome 13. The first case had a t(6;13), and the second had a t(1;13). Abnormalities of chromosome 13 mainly involving loss of band 13q14 have been described in hematologic malignancies. In both our cases band 13q14 did not participate in the deleted segment. PMID- 1933816 TI - Chromosome changes in a squamous cell carcinoma of the vagina. AB - The findings on direct chromosome preparations of a moderately differentiated squamous cell carcinoma of the vagina are described. Most counts were in the range 82-86. Eight markers were present in at least five of six metaphases karyotyped: 3p- (1-2 copies); i(5p) or possibly 5q- (2-3 copies); i(8q) (2 copies); 11q- (2-4 copies); 15p+ (1-2 copies), a probable 18q- (1 copy), 22p+ (1 copy), and minute acrocentric (2-4 copies). Numerical changes included extra copies of chromosomes 7 and 13, but only one copy of chromosome 11 was present. PMID- 1933818 TI - An endometrial stromal sarcoma with clonal cytogenetic abnormalities. AB - Cytogenetic analysis of a low-grade metastatic endometrial stromal sarcoma in a 58-year-old woman revealed translocations involving both homologues of chromosome 7 with chromosomes 13 and 17, respectively, and an interstitial deletion of the long arm of chromosome 11. The karyotype of the tumor was 46,XX,t(7;13)(q11.1;p13),t(7;17)(p21;q12),del(11)(q13q21). PMID- 1933817 TI - Ewing's sarcoma t(11;22) in a case of acute nonlymphocytic leukemia. AB - Chromosome analysis of bone marrow cells from a patient with acute nonlymphocytic leukemia M2 revealed the translocation t(11;22)(q24;q12) usually associated with Ewing's sarcoma. Molecular investigations ruled out the possibility that this was a variant Philadelphia translocation with breakpoints in the major breakpoint cluster region. Although cytogenetic analysis was not available at diagnosis, this abnormality was found both pre- and postallogeneic bone marrow transplant. PMID- 1933820 TI - Cytogenetic studies in patients with multiple myeloma. AB - Fourteen patients diagnosed as having multiple myeloma were studied cytogenetically. In eight patients a sufficient number of metaphases was obtained and four of them showed abnormal karyotypes of bone marrow cells. Hypodiploidy was a consistent finding, as was the involvement of chromosome 9. PMID- 1933819 TI - Multiple and complex abnormalities in a case of alveolar soft-part sarcoma. AB - Chromosomal analysis of two pulmonary metastases from a 25-year-old male with alveolar soft-part sarcoma of the right lower extremity revealed multiple and complex chromosomal abnormalities. The rearrangements included deletions and translocations affecting chromosomes 1, 2, 3, 10, 11, 14, 15, and 16. Trisomy of chromosome 12 and loss of chromosome 17 was also observed. PMID- 1933821 TI - A variant (2;13) translocation in rhabdomyosarcoma. AB - Cytogenetic analysis of a right buttock mass from a 5-year-old boy showed translocation between an inverted chromosome 1 and a chromosome 13 as the sole cytogenetic abnormality. The breakpoint 13q14 appears to be the same as in previously reported cases of rhabdomyosarcoma (mostly of the alveolar type), but does not show involvement of 2q37. We suggest that this translocation may be a variant of the classical t(2;13)(q37;q14) found in rhabdomyosarcoma. PMID- 1933822 TI - Cytogenetic studies of five primary esophageal cancers. AB - In direct preparation of five primary esophageal cancers, chromosomes 1, 3, and 12 were most frequently involved in structural abnormalities; 12p- was consistently seen in all five cases and, thus, could be considered as one of the characteristic chromosome changes in esophageal cancer. Moreover, 2p-, 4p-, and 7q- were seen in three cases. PMID- 1933824 TI - Cytogenetic findings in a pleomorphic xanthoastrocytoma. AB - We report a pleomorphic xanthoastrocytoma with an abnormal clonal cell line of 48,XY, +3, +5, -20, -22, +der(7)t(7;?)(p22;?), +der(20)t(15;20)(q11;q13). PMID- 1933823 TI - Chronic myelogenous leukemia after treatment with 131I for thyroid carcinoma. Report of a case and review of the literature. AB - A patient who developed Philadelphia chromosome-positive chronic myelogenous leukemia (CML) 5 years after successful treatment for thyroid carcinoma, is reported. The Philadelphia chromosome was the typical 9;22 translocation. Southern blot analysis showed breakpoint cluster region rearrangement as observed in classical CML. Up to now, only two cases of CML have been reported following treatment for thyroid carcinoma. This rare complication has also been described after therapy for other malignancies. At present, it is not clear whether the development of CML after thyroid carcinoma represents a therapy-induced complication, a coincidence, or an increased susceptibility to secondary malignancies due to the malignant process itself. PMID- 1933825 TI - Cytogenetic analysis of primary neuroblastoma with del(1), del(14), hsr, and dmin chromosomes. AB - The results of a direct cytogenetic tumor analysis in a 2 1/2-year-old girl with metastatic neuroblastoma are presented in this paper. Investigations established a modal karyotype of 46 chromosomes with several marker chromosomes. Besides del(1)(p31), hsr, and dmin chromosomes in all the cells analyzed, terminal deletion of the long arm of chromosome 14 was also identified. Malignant cells were thus monosomic for segment 14q24----qter. PMID- 1933826 TI - Effect of recombinant human IL-3 on the mitotic index and karyotype of hemopoietic cells. AB - The proliferative induction by hemopoietic growth factors may provide a useful tool to improve the mitotic yield of hemopoietic cells, allowing a more accurate cytogenetic analysis in hematologic malignancies. For such a purpose, we studied the effects of the recombinant human IL-3 (rhIL-3) on the mitotic index and the karyotype of bone marrow cells from 14 patients with myelodysplastic (MDS) and myeloproliferative syndromes (MPS). The mitotic response to IL-3 of normal bone marrow samples was also evaluated. Total bone marrow cells were cultured for 24 to 72 hours either in presence or absence of rhIL-3. In most cases, IL-3- stimulated samples showed a considerably higher (4-70 times) mitotic index than unstimulated controls. Although a great patient-to-patient variability was observed, a common pattern of mitogenic response to IL-3 emerged among MPS, MDS, and normal cases. At 48 hours of incubation, the mean mitotic index from MPS and MDS cases stimulated with IL-3 was significantly higher (p less than 0.01) than unstimulated controls, whereas the mean mitotic increase from normal samples did not reach statistical significance (p greater than 0.1). Even though not statistically evaluable, a similar trend of response was observed at 24 and 72 hours of culture. Chromosome studies of MPS and MDS cases showed the same karyotype either in stimulated and unstimulated samples. PMID- 1933827 TI - Interphase cytogenetics of a male breast cancer. AB - Direct interphase cytogenetic analysis was performed on nuclei from a male breast tumor using fluorescence in situ hybridization (FISH). DNA probes specific for repetitive pericentromeric regions on chromosomes 1, 7, 9, 11, 15, 17, 18, X, and Y were used to determine chromosome copy numbers in interphase tumor cells. Copy number distributions varied greatly between chromosomes, showing major tumor populations with on (Y), two (X,9), three (11, 15, 18), and four (1, 7, 17) copies of the pericentromeric targets. The X chromosome was present in two copies in 84.7% of tumor nuclei, with the balance being primarily monosomic. Normal skin fibroblasts cultured from the same patient showed 99% monosomy X. The Y chromosome showed a minor population (12%) with two copies. The DNA index of the tumor was 2.0 as determined by flow cytometry. The proliferative activity of the tumor cells was simultaneously analyzed using detection of in vivo bromodeoxyuridine (BrdU) incorporation. The BrdU labeling index was 13.2%. PMID- 1933828 TI - Cytogenetic features of childhood acute lymphoblastic leukemia. A concordance study and a Pediatric Oncology Group study. AB - Cytogenetic analysis yields important objective information that has been shown to correlate with both patient response to therapeutic intervention and patient survival. Bone marrow samples are submitted to a common reference laboratory for cytogenetic analysis from children with newly diagnosed acute lymphoblastic leukemia (ALL) registered on frontline Pediatric Oncology Group (POG) therapeutic studies (classification 8600 series). A portion of the sample from the Texas Children's Hospital (Houston, TX) a POG affiliate, was also submitted to a local cytogenetics laboratory for analysis. This study retrospectively compares karyotypic data and methods from the Laboratory of Medical Genetics, University of Alabama at Birmingham (reference laboratory) with those of the Kleberg Cytogenetics Laboratory at the Baylor College of Medicine (local laboratory) over a 35-month period to evaluate the effect of differences in specimen procurement, handling, and laboratory methodology on yield of cytogenetic information. Each laboratory was able to identify clonal abnormalities in 72% of cases examined during the last year of the study. When these data were combined, the overall detection rate of clonal abnormalities was 87.5%. Utilizing the same bone marrow aspirate from 73 children, this study demonstrates that cytogenetic methodology significantly affects the yield of identifiable clonal abnormalities, while variables such as overnight shipping have no discernable effect. This study also supports the contention that central laboratory testing effectively yields information critical to ongoing large-scale research endeavors. PMID- 1933829 TI - Alveolar rhabdomyosarcoma with del(13q14). AB - We report a case of disseminated alveolar rhabdomyosarcoma, where chromosome analysis showed a deletion of chromosome 13(q14). This breakpoint is involved in the t(2;13)(q37;q14) previously reported in cases of rhabdomyosarcoma, but this is the first reported case in whom this deletion occurs without involvement of chromosome 2. The possible oncogenic role of the retinoblastoma (RB1) gene located at the breakpoint is discussed. PMID- 1933830 TI - Unusual t(3;12)(q28;q13) in childhood acute lymphoblastic leukemia. AB - In this article we report a case of a 7-year-old boy affected by acute lymphoblastic leukemia of the common type. Bone marrow examination at diagnosis showed a reciprocal translocation between the long arm of chromosome 3 and the long arm of chromosome 12. This previously unpublished translocation is discussed and compared to the findings in the current literature. PMID- 1933831 TI - Variant translocation (3;inv(16)) in acute myelomonocytic leukemia with eosinophilia. PMID- 1933832 TI - Trisomy 4 and 9 in a case of AML-M2 type. PMID- 1933833 TI - Hodgkin's disease and secondary Philadelphia chromosome positive chronic myelogenous leukemia. PMID- 1933834 TI - Endogenous secretion of epidermal growth factor peptides stimulates growth of DU145 prostate cancer cells. AB - The growth rate of DU145 prostate cancer cells in vitro is slowed considerably by changing the growth medium every 24 h, suggesting dependence upon endogenously secreted growth factors. Because previous studies have identified epidermal growth factor (EGF) in the conditioned medium from DU145 cells, [35S]labeled EGF was selectively immunoprecipitated from the culture medium at 24-h intervals for quantitation. Under the culture conditions used, there was an initial phase of slow growth, the EGF level secreted per cell was highest on day 3 after plating, and an increase in cell number was most evident between days 3 and 4. Finally, growth was assayed under culture conditions where the medium was replaced every 24 h with fresh medium in the absence or presence of 10 ng/ml added EGF. The EGF was able to increase the cell growth up to the levels seen in cultures where the medium was unchanged during the entire period. We interpret these results as evidence that endogenously secreted EGF-like growth factors participate in an autocrine growth stimulation of DU145 cells. PMID- 1933835 TI - Cell growth simulations predicting polyclonal origins for 'monoclonal' tumors. AB - Studies showing the clonal identity of various tumors have led to the belief that most tumors originate from a single cell. It is shown by Monte Carlo computer simulations that monoclonality can evolve from minor differences either in cell cycle time or in the probability of cell death in a polyclonal 'founder' population. If cells divide continuously without cell death (exponential clonal growth), a triclonal population with three starting cells (cell cycle times 0.9 days, 1 day and 1.1 days) converges to near-monoclonality in 100 generations. For cell cycle times of 0.9 days, 1.1 days and 1.1 days, and cell death probabilities of 0.45 and 0.46, populations tend toward monoclonality while the tumor is still small (less than 3 mm3). PMID- 1933836 TI - The anomalous biological activity of nitroso-2-oxopropyl compounds. AB - The carcinogenic action of a set of N-nitroso compounds containing the 2 oxopropyl group was considered in relation to their metabolism and their activity as alkylating agents for DNA. In contrast with the great carcinogenic potency of methylnitrosourea and ethylnitrosourea, comparable with the corresponding dialkylnitrosamines, 2-oxopropylnitrosourea is a weak carcinogen with a limited range of target organs in rats and hamsters. 2-Oxopropylnitrosochloroethylurea was somewhat weaker than 2-oxopropylnitrosourea and similarly induced spleen hemangiosarcomas in hamsters, but few tumors of any kind in rats. The relatively much more potent carcinogenicity of nitrosobis-(2-oxopropyl)amine, nitroso-(2 hydroxypropyl) (2-oxopropyl) amine and methylnitroso-2-oxopropylamine suggests that the activity of an oxopropylating agent is not involved in carcinogenesis by nitroso-2-oxopropylamines. The nitrosamines are likely to undergo extensive metabolism to form proximate carcinogenic moieties, probably including the methyldiazonium ion, which are responsible for the induction of a broad range of tumors in rats and hamsters. These include tumors of the liver, pancreas ducts, lung and nasal mucosa in hamsters, and esophagus, liver, lung, thyroid, kidney, trachea, bladder and nasal mucosa in rats. PMID- 1933837 TI - The thalidomide analog, EM 12, enhances 1,2-dimethylhydrazine-induction of rat colon adenocarcinomas. AB - Young male Sprague-Dawley rats in 3 groups were fed a basal diet supplemented with 0.10 wt. % each of thalidomide and its imide-analog of much higher teratogenicity, EM 12. Following an induction period of 17 days on the diets, all animals were injected subcutaneously with 1,2-dimethylhydrazine at 20 mg/kg for a total of 20 weekly doses and killed on week 18 after the 20th injection. The total number of colon adenocarcinomas and their occurrence in the proximal and distal portions for the thalidomide-treated rats were similar to those of the respective controls. However, the EM 12-fed group elicited statistically significant increases both in the total and ascending colon-based adenocarcinomas as compared with the control findings, in keeping with its greater teratogenicity and embryotoxicity. The numbers of small intestinal adenocarcinomas were equally higher in the imide-fed groups in contrast to the control frequency. PMID- 1933838 TI - A study of betel quid carcinogenesis. IX. Comparative carcinogenicity of 3 (methylnitrosamino)propionitrile and 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone upon local application to mouse skin and rat oral mucosa. AB - The Areca-derived 3-(methylnitrosamino)propionitrile (MNPN) was tested for its tumor initiating activity on mouse skin and for its tumorigenic potential in the oral mucosa of rats. On mouse skin, like the otherwise strongly carcinogenic, tobacco-specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), MNPN showed only weak local tumor initiator activity. However, the application of MNPN to mouse skin led also to multiple distant tumors in the lungs of the animals. Twice daily swabbing of the oral cavity of rats with aqueous solutions of MNPN or NNK for up to 61 weeks led only to one oral tumor in each group of 30 animals. Yet, these N-nitrosamines proved again to be strong organ-specific carcinogens. Thus, MNPN induced nasal tumors in 80% of the rats and lung adenomas in 13%, liver tumors in 10% and papillomas of the esophagus in 7%. NNK induced lung adenoma and/or adenocarcinoma in 90%, nasal tumors in 43% and liver adenomas/adenocarcinomas in 30% of the rats. These results confirm previous observations that, independent of the site and mode of application, MNPN and NNK remain strong organ-specific carcinogens in laboratory animals. PMID- 1933839 TI - Hyperthermic sensitivity and cholesterol levels of mammalian cell lines in culture. AB - In this study, we asked whether cholesterol contents were specifically correlated with cellular sensitivity to hyperthermia. To examine this possibility, we employed two isogenic mammalian cell lines, Chinese hamster V79 cell line and its amphotericin B-resistant (AMBr) cell line. AMBr cells had a decreased content of membrane sterols in comparison with V79 cells. Clonogenic assays showed that AMBr cells were more sensitive to hyperthermic treatment at 45 degrees C than V79 cells. Cholesterol contents were increased in AMBr cells by exposure to liposomes containing 1:1 lecithin-cholesterol, and the sterol level was comparable to that of V79 cells. In comparison with untreated AMBr cells, AMBr cells were more resistant to hyperthermia at 45 degrees C when incubated with liposomes containing cholesterol. Treatment of V79 cells with oxygenated sterol, a potent inhibitor of endogeneous sterol synthesis, sensitized the hyperthermic cytotoxicity. Our present data present the hypothesis that cellular cholesterol contents are closely correlated with cellular heat toxicity. PMID- 1933840 TI - Inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis and of in vivo formation of mammary DMBA-DNA adducts by rosemary extract. AB - The effect of dietary intake of an extract of the spice plant Rosmarinus officinalis L. on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis and on the in vivo formation of mammary DMBA-DNA adducts was evaluated. Supplementation of a semi-purified diet with 1.0% (by wt.) rosemary extract resulted in a significant (47%) decrease in mammary tumor incidence compared to controls. In subsequent studies, dietary supplementation with 0.5% and 1.0% rosemary extract inhibited total in vivo binding of DMBA to mammary epithelial cell DNA by an average of 42%. This decrease in total binding was not due to a uniform decrease in the formation of all mammary DMBA-DNA adducts. The formation of two major adducts derived from the anti-diastereomer of DMBA and bound to deoxyguanosine (anti-dGuo) was significantly decreased at both dietary rosemary concentrations. The formation of the syn-dGuo adduct also was inhibited, whereas formation of the syn-dAdo adduct was unaffected by consumption of the rosemary extract. These studies suggest that use of rosemary extract and its individual antioxidative constituents as chemopreventative agents for experimental mammary tumorigenesis warrant further investigation. PMID- 1933841 TI - Intervention strategies for smoking cessation. The role of oncology nursing. AB - The role of oncology nurses concerned with the health effects of cigarette smoking may often be defined as dealing with the morbidity and mortality associated with tobacco use--caring for individuals diagnosed with tobacco related malignancies. As current treatment methods of many of these malignancies offer little hope of cure, oncology nurses need to diverge from these traditional roles and include a focus on primary prevention activities. An essential component of these activities is a knowledge of smoking cessation education strategies and an understanding of the methods that motivate and assist individuals to quit smoking. PMID- 1933842 TI - Identification of stressors, level of stress, coping strategies, and coping effectiveness among Egyptian mastectomy patients. AB - The purpose of this study was to identify stressors, level of stress, coping strategies, and coping effectiveness in Egyptian female mastectomy patients. A total of 64 women who had had mastectomies participated in the study. Coping effectiveness was measured by McNett's Coping Effectiveness Questionnaire (MCEQ). Factor analysis and reliability measures were established on MCEQ using the study sample. Data were collected using a structured interview method. Participants were also asked about age, education, and time since mastectomy. These data were examined in an effort to predict coping effectiveness. The participants reported five stressors: hope for cure, treatment effectiveness, fear of the unknown, progression of the disease, and pain. The treatment effectiveness stressor had the highest mean level of stress. There was a significant difference in the level of stress among the five stressors. Coping strategies reported were categorized into four groups: faith, compliance with the medical regimen, seeking information and social support, and self-distraction. Coping effectiveness was significantly and positively correlated with age and time since mastectomy, which accounted for 35% of the variance in coping effectiveness. Findings suggest that continuing assessments of Egyptian mastectomy patients' needs, further research studies, and an intervention program to ameliorate cancer-related anxiety and to help cancer patients cope effectively may be helpful. PMID- 1933843 TI - Contracting cancer and coping with it. Patients' experiences. AB - The aim of this exploratory study was to provide information for use in improving the nursing care of cancer patients in Finland. This was done by describing the adaptation demands and the means used for coping with the situation. Material was assembled by open-ended questions in a questionnaire and by a semistructured interview centered on four themes. The material comprised 123 patients who had different types of cancer, were at various stages in the disease, and were living in or around a city in Finland. Interviews were conducted with 43 of these patients. The adaptation demands imposed by cancer were apparent at the time of observation of the first symptoms and reporting for treatment. Contracting cancer had come as a shock to 68% of the patients, and they had reacted by employing various defense mechanisms such as denial and rejection to cope with this stage. The results of the early feelings of the patients when they first heard that they had cancer were coded into three conceptual categories that followed each other: use of defense mechanisms, realization of feelings, and action aimed at management of the feelings caused by cancer. The subsequent methods of coping included emotional evaluation of their situation in life, comparison with earlier experiences and those of other cancer patients, and appeals for social welfare assistance. PMID- 1933844 TI - Critical nursing behaviors in care for the dying. AB - A beginning list of seven critical nursing behaviors in care for the dying was identified in a qualitative study. Ten experienced palliative care nurses and 10 nurse educators were asked to describe situations in which a student or graduate nurse had displayed very positive or very negative attitudes to care for the dying. Behaviors identified after content analysis of transcribed interviews were responding during death scene, providing comfort, responding to anger, enhancing personal growth, responding to colleagues, enhancing quality of life during dying, and responding to the family. Three of these behaviors were not well described in the nursing literature. PMID- 1933845 TI - Development of the inventory of functional status-cancer. AB - The purpose of this article is to report the development and psychometric testing of the Inventory of Functional Status-Cancer (IFS-CA). The IFS-CA was developed to measure functional status in women with cancer. The questionnaire includes four subscales measuring the extent to which the woman continues her usual household and family, social and community, personal care, and occupational activities. Content validity was established at 98.5%. Internal consistency reliability testing used a sample of 100 women receiving treatment for cancer. Internal consistency reliability using average correlations for the subscale item to subscale total scores ranged from 0.56 to 0.82. Subscale to total IFS-CA score correlations ranged from 0.73 to 0.92. Test-retest reliability used a sample of 17 women who had completed treatment for cancer. The coefficients ranged from 0.43 to 0.96 for the four subscales. Initial construct validity testing was accomplished by examination of subscale correlations and by comparing the functional status of women in active treatment for cancer with those who had completed treatment. The study's findings reveal content validity, internal consistency, test-retest reliability, and beginning construct validity; thus, they demonstrate strong evidence for further development and testing of the IFS CA's construct validity. PMID- 1933846 TI - Nutrition support. Making the difficult decisions. AB - Weight loss and cachexia are common characteristics associated with the cancer patient. Although the wasted appearance seems the same in each person, the causes are varied. Studying a patient's history and identifying surgical causes to weight loss or weight loss as a result of treatment complications assists in the consideration of nutritional support. Nutritional parameters combined with the oncology nurse's knowledge of the patient, disease process, and treatment side effects place the nurse in the position to help identify options for nutritional support. The oncology nurse's expertise assists in the decision making process, since it is often not appropriate to institute nutritional support in the inpatient setting nor extend it to the home situation. Objective assessment parameters for home parenteral nutrition assist the nurse in making some of these decisions. The conflicts that arise within the decision making process are usually not clearcut nor easily resolvable. Home parenteral nutrition brings to the forefront requirements and variables that are often not consciously addressed when hyperalimentation is instituted in the inpatient setting. PMID- 1933847 TI - Walking program for people with cancer. Getting started. AB - Having the energy to maintain functional independence and social roles is an important component of quality of life in cancer patients. Unnecessary bedrest and prolonged sedentarism can contribute significantly to the development of fatigue and may result in rapid and potentially irreversible losses in energy and functioning. Walking is an important self-care activity that can counter some of the debilitating effects of disease, treatment, and inactivity. Research on exercise for ambulatory cancer patients has been limited to moderate intensity, interval, supervised exercise programs on cycle ergometers. However, lower intensity walking can be used as a self-care intervention for individuals or groups. Cancer patients often ask questions about what kind, frequency, duration, and intensity of exercise they should perform. By teaching self-care techniques, such as keeping a walking diary and pulse monitoring to regulate activity, nurses can help patients develop safe activity practices. I also present guidelines and precautions related to safe exercising by ambulatory patients during and after treatment for cancer. PMID- 1933848 TI - Phase I and pharmacokinetic study of hepsulfam (NSC 329680). AB - Hepsulfam (NSC 329680), a bifunctional alkylating agent structurally related to busulfan, has entered clinical trial based on its broader preclinical antitumor activity compared with that of busulfan and its i.v. formulation which may circumvent the many problems arising from the p.o. administration of busulfan, such as significant individual differences in bioavailability. In this Phase I study, 53 patients received 95 courses of hepsulfam at doses ranging from 30 to 480 mg/m2 administered i.v. over 30 min every 28 days. Hematological toxicity was dose limiting. Leukopenia and thrombocytopenia were dose related, delayed in onset, and sustained for long durations. Toxicity was cumulative in most patients receiving more than one course. This pattern of myelosuppression suggests that hepsulfam is cytotoxic to hematopoietic stem cells. Although hematological toxicity was not particularly severe during most courses, its lengthly duration precluded the prompt administration of subsequent courses. Minimal nonhematological effects were observed. Pharmacokinetic studies revealed that the clearance rate of hepsulfam is linear over the dose range studied and that its plasma disposition is biphasic with mean alpha and beta half-lives of 19 +/- 18 (SE) min and 337 +/- 248 (SE) min, respectively. The area under the plasma clearance curve correlated with the percentage of change in WBC using a sigmoidal Emax model and with the duration of thrombocytopenia in patients with hematological toxicity. Based on the protracted duration of the toxicity of multiple doses that were greater than 210 mg/m2, the recommended starting dose for Phase II trials is 210 mg/m2. However, these trials should be pursued with caution because of the protracted nature of hepsulfam's myelosuppression. Because hepsulfam produced minimal nonhematological toxicity, substantial dose escalation above 480 mg/m2 may be possible with hematopoietic stem cell support. PMID- 1933849 TI - Development and field-test validation of an assay for DNA repair in circulating human lymphocytes. AB - A method for measuring nucleotide excision repair in response to UV irradiation and chemical-induced DNA damage has been developed, validated, and field tested in cultured human lymphocytes. The methodology is amenable to population-based screening and should facilitate future epidemiological studies seeking to investigate associations between DNA repair proficiency and cancer susceptibility. The impetus for such endeavors derives from the suggestion that the high incidence of skin cancer in the genetic disorder xeroderma pigmentosum is manifested as a result of the reduced capacity of patients' cells to repair DNA damaged by UV-mimetic agents. For the assay, damaged, nonreplicating, recombinant plasmid DNA harboring a chloramphenicol acetyltransferase (cat) reporter gene is introduced into lymphocytes by using a DEAE-dextran/DNA complex short-term transfection conditions. Excision repair of the damaged bacterial cat gene is monitored proportionately as a function of reactivated CAT enzyme activity following a 40-h repair/expression incubation period. The validity of the approach was indicated by the ability of the assay to discriminate xeroderma pigmentosum virus-transformed lymphocyte cell lines of both severe (complementation groups A and D) and moderate (complementation group C) excision repair deficiencies from repair-proficient cell lines. Similar results were observed when a mitogen-stimulated peripheral blood lymphocyte culture from an xeroderma pigmentosum A patient was assayed concurrently with mitogen-stimulated peripheral blood lymphocytes obtained from healthy individuals. Adaptation of this DNA repair assay as a field test in a pilot-tested select group of basal cell carcinoma patients and cancer-free controls led to the preliminary identification of a specific subset at risk for this disease as a consequence of significant reduction to the repair of photochemically (UV)-damaged plasmid DNA. PMID- 1933851 TI - In vivo measurements of intratumoral metabolism, modulation, and pharmacokinetics of 5-fluorouracil, using 19F nuclear magnetic resonance spectroscopy. AB - In vivo 19F nuclear magnetic resonance spectroscopy was used to monitor and measure 5-fluorouracil and some of its cytotoxic anabolites directly in rats bearing the Walker 256 adenocarcinoma by using a 4.7-T horizontal bore magnet. A two-compartment subsystem model was used to estimate intratumoral transfer parameters. The apparent rate of formation of the nucleosides/tides in the tumor, K21, changed following methotrexate pretreatment, from a value of 6.4 +/- 2.4 to 15.5 +/- 5.0. These values were statistically significant to P less than 0.01. This 2-compartment model was validated by excising the tumors and measuring the 19F content of the acid soluble and the RNA fractions. The increase of the mean K21 value (2.4) estimated in vivo correlated favorably with the increase of the levels of the fluorinated nucleosides/nucleotides (2.2) observed by in vitro analysis. The in vitro measurements also revealed that the increase in the fluorinated nucleosides was accompanied with a similar increase in 5-fluorouracil incorporation into the RNA fraction, which suggests that increases or decreases in the relative intensity of the fluorinated nucleoside/nucleotide signals observed in vivo could be indicative of similar changes of the nuclear magnetic resonance invisible fluorinated RNA. The present study documents that it is now possible to estimate the pharmacokinetic behavior of 5-fluorouracil and of its active metabolites at its target site, tumor tissue, by using noninvasive measurements. Such measurements may provide useful means of assessing, during treatment, the possible effect of 5-fluorouracil on the tumor, and its response to treatment, both when used by itself as well as a function of biochemical modulation. PMID- 1933850 TI - p53 gene mutations in gastric cancer metastases and in gastric cancer cell lines derived from metastases. AB - Structural alterations of the p53 gene were investigated in tissue specimens of gastric and cervical cancers and in cell lines of gastric, esophageal, and cervical cancers, by polymerase chain reaction-single-strand conformation polymorphism analysis. Two of the four gastric cancer metastases and four of the eight cell lines originally established from gastric cancer metastases were found to have p53 gene alterations in the exon 5 to 11 region; point mutations and amino acid replacements were detected in a liver and an ovary metastasis at exon 7, in the TMK1 and MKN1 cell lines at exon 5, and in the OKAJIMA cell line at exon 10. The normal allele was not found in these cell lines. In the KATO-III cell line, gross deletion and rearrangement of the p53 gene were noted. However, no p53 mutations were identified in 19 primary lesions of gastric cancer, suggesting that the p53 gene abnormality preferentially occurs in the advanced stages of gastric cancer. In contrast to the gastric cancer, none of the 13 esophageal cancer cell lines, including two cell lines established from metastases, and none of the four cervical cancer cell lines showed any aberration in exons 5 to 11 of the p53 gene. During the course of the study, a novel polymorphism in intron 7 of the p53 gene was found, which can be recognized by restriction enzyme digestions of the polymerase chain reaction product. PMID- 1933852 TI - Nickel(II)- and cobalt(II)-dependent damage by hydrogen peroxide to the DNA bases in isolated human chromatin. AB - Nickel compounds are known to be carcinogenic to humans and animals. Cobalt compounds produce tumors in animals and are probably carcinogenic to humans. The mechanisms of the carcinogenicity of these metal compounds, however, have remained elusive. In the present work, we have investigated the ability of Ni(II) and Co(II) ions in the presence of H2O2 to cause chemical changes in DNA bases in chromatin extracted from cultured cells of human origin. Eleven modified DNA bases in chromatin were identified and quantitated by the use of gas chromatography-mass spectrometry. 2-Hydroxyadenine (isoguanine), which has not previously been shown to occur DNA or chromatin, was also identified. Products identified were typical hydroxyl radical-induced products of DNA bases, suggesting that the hydroxyl radical was involved in their formation. This idea was supported by partial inhibition of product formation by typical scavengers of hydroxyl radical. Partial inhibition of product formation indicated a possible "site-specific" formation of hydroxyl radical by unchelated Ni(II) and Co(II) ions bound to chromatin. Although treatment of chromatin for 1 h with Co(II)/H2O2 caused formation of significant amounts of products, treatment with Ni(II)/H2O2 required incubation times of more than 5 h and an increase in Ni(II) concentration before increases in product amounts above background levels became detectable. In both cases, ascorbic acid did not increase product yields. Glutathione at a physiologically relevant concentration had little overall effect on DNA base modification. Superoxide dismutase increased the yields of most products. Chelation of Ni(II) and Co(II) ions with EDTA almost completely inhibited product formation. Ni(II) in the presence of H2O2 produced greater base damage to the DNA in chromatin than to isolated DNA, unlike other metal ions tested. DNA damage in chromatin caused by Ni(II) and Co(II) ions in the presence of H2O2 may contribute to the established genotoxicity and carcinogenicity of these metal ions. PMID- 1933854 TI - Pyrrolidino-4-iodotamoxifen and 4-iodotamoxifen, new analogues of the antiestrogen tamoxifen for the treatment of breast cancer. AB - New tamoxifen analogues were tested for their antiproliferative activity both in vitro and in vivo. Binding studies showed that both 4-iodotamoxifen and pyrrolidino-4-iodotamoxifen and 2.5-fold higher affinities for the estrogen receptor compared with tamoxifen. Pyrrolidino-4-iodotamoxifen was also 1.5-fold more effective in causing inhibition of estrogen-induced growth of MCF-7 cells compared with tamoxifen at 10(-6) M. The 4-iodotamoxifen analogue was similar to tamoxifen in its inhibitory action at 10(-6) M. Antiproliferative activities of these drugs were tested using the nitrosomethylurea-induced rat mammary tumor model. Pyrrolidino-4-iodotamoxifen caused regression in 92% of rats, whereas tamoxifen caused regression in 75% of rats. The agonist activity of the analogues was determined using the immature rat and mouse uterotrophic assays. Both tamoxifen and 4-iodotamoxifen had similar partial agonist activity, and this was greater than that seen with pyrrolidino-4-iodotamoxifen. Furthermore, pyrrolidino 4-iodotamoxifen caused a dose-dependent inhibition of estrogen-induced vaginal cornification, whereas tamoxifen and 4-iodotamoxifen did not. These studies demonstrate that pyrrolidino-4-iodotamoxifen is more effective than tamoxifen in inhibiting tumor regression and that its reduced uterotrophic activity and increased estrogen receptor binding may give it significant clinical advantages over the parent compound. PMID- 1933853 TI - Nitrosamine-induced cancer: selective repair and conformational differences between O6-methylguanine residues in different positions in and around codon 12 of rat H-ras. AB - Mammary and skin tumors induced in rodents by N-methyl-N-nitrosourea treatment have a G:C to A:T transition mutation in codon 12 of H-ras, probably resulting from alkylation of O6 of guanine by the carcinogen. This codon contains two guanines (5'-GGA-3'), but mutations are observed only in the central base pair of this codon. The same selectivity for mutations of -GGA-sequences has also been observed in Escherichia coli. It is known that the central G in the sequence GGA is a preferred site for alkylation, but the magnitude of chemical selectivity is insufficient to provide a complete explanation for the biological observation which is still unexplained. We have measured accurate rates of repair by the E. coli and gene O6-alkylguanine-DNA-alkyltransferase of an O6-methylguanine in various positions in chemically synthesized 15-base pair DNA duplexes having the H-ras sequence. The rate of repair varied 25-fold, depending on the sequence flanking the methylguanine. An O6-methylguanine in position 2 of codon 12 was the least well repaired. The combination of this slow repair and sequence selectivity in alkylation appears to be the explanation for the selective mutation of this position. Using an antibody to probe the accessibility of the O6 methyldeoxyguanosine, it was shown that the rate of repair is a reflection of the conformation of the sequence containing the alkylated base, because the avidity constants between antibody and O6-methylguanine were also dependent on the sequence flanking the methylguanine, with the most rapidly repaired O6 methylguanines being those most easily bound by the antibody. PMID- 1933855 TI - Antitumor activity of Fab' and IgG-anti-CD22 immunotoxins in disseminated human B lymphoma grown in mice with severe combined immunodeficiency disease: effect on tumor cells in extranodal sites. AB - The antitumor effects of two anti-CD22 ricin A chain-containing immunotoxin (IT) constructs were compared in mice with severe combined immunodeficiency disease with human Daudi cell tumors (SCID-Daudi mice). SCID-Daudi mice develop disseminated lymphoma that clinically resembles African Burkitt's lymphoma, i.e., extranodal disease including infiltration of the vertebral column and spinal canal. In the absence of treatment, the mean survival time of SCID-Daudi mice was 45.9 +/- 4.3 days. The mice was given injections of a dose of IT equal to 40% of the 50% lethal dose. The ITs consisted of either IgG or Fab' fragments of mouse anti-CD22 antibody coupled to deglycosylated ricin A chain (dgA). Both ITs were potent and specific and inhibited protein synthesis in Daudi cells in vitro by 50% at concentrations of 1.2 x 10(-12) (IgG-dgA) and 1.3 x 10(-11) M (Fab'-dgA). When administered to mice beginning 1 day after inoculation with tumor cells, both ITs extended the mean survival time, to 87.2 +/- 18.9 days (IgG-dgA) or 57.9 +/- 3.8 days (Fab'-dgA). The latter represented the killing of 2 logs of Daudi cells, and the former 4 logs. IgG antibody alone killed 1 log of tumor cells. The IgG-dgA had an antitumor effect even when administered 20-23 days after tumor inoculation. Gross and histological examinations of IT-treated tumor-bearing mice showed a marked decrease in the number and size of neoplastic foci in both lymphoid organs and extranodal sites. PMID- 1933856 TI - Glycosylation at the Fab portion of myeloma immunoglobulin G and increased fucosylated biantennary sugar chains: structural analysis by high-performance liquid chromatography and antibody-lectin enzyme immunoassay using Lens culinaris agglutinin. AB - An antibody-lectin enzyme immunoassay technique which had been developed for the analysis of sugar chains of alpha-fetoprotein (N. Kinoshita et al., Clin. Chim. Acta, 179: 143-152, 1989) was used for analysis of sugar chains of myeloma immunoglobulin G (IgG). The IgG sugar chains of four of nine patients with myeloma were found to be highly reactive to Lens culinaris agglutinin as compared with those of six normal controls and 177 patients without myeloma. This reflected a high L. culinaris agglutinin/concanavalin A ratio. The IgGs of these patients were found to have highly sialylated, fucosylated, and bisected biantennary sugar chains at Fab portions as judged by the lectin-blotting technique as well as by high-performance liquid chromatography analysis. These results indicate that some of the myeloma IgG proteins undergo unusual glycosylation processes. PMID- 1933857 TI - Effect of psoralen plus ultraviolet A radiation on in vivo growth of melanoma cells. AB - Exposure of murine skin to UVB (280-320 nm) radiation accelerates the outgrowth of melanoma cells implanted into the irradiated site. Because many of the biological effects of psoralen plus UVA (320-400 nm) radiation (PUVA) resemble those of UVB radiation and because PUVA therapy is used extensively in the treatment of cutaneous diseases in humans, we determined the effect of PUVA on the growth of transplanted murine melanoma cells. Unshaved C3H/HeN(MTV-) mice were treated twice each week for 3 weeks with 0.4 mg 8-methoxypsoralen i.p. plus 4.25 kJ/m2 UVA radiation; syngeneic K1735 melanoma cells were then injected s.c. into the external ear. This treatment stimulated the outgrowth of the melanomas compared to that in untreated mice and mice treated with 8-methoxypsoralen or UVA alone. The use of a nonphototoxic, monofunctional psoralen plus UVA was equally effective, indicating that neither phototoxicity nor the ability to form DNA crosslinks was required for this effect. In vitro treatment of a murine keratinocyte cell line PAM 212 with PUVA caused the release of soluble factors that, when mixed with K1735 melanoma cells prior to injection, stimulated their outgrowth in vivo. These studies demonstrate that PUVA treatment can contribute to the pathogenesis of melanoma by exerting a stimulatory effect on the outgrowth of melanoma cells. Furthermore, they suggest that this effect may result from the ability of PUVA to cause the release of stimulatory factors from keratinocytes. PMID- 1933858 TI - Effects of transforming growth factor beta on the anchorage-independent growth of murine epithelial JB6 cells. AB - The work described in this paper demonstrates that transforming growth factor beta (TGF-beta) induces the soft agar growth of murine epidermal JB6 clone 41 (Cl 41) cells. In this regard, TGF-beta is more effective than either 12-O tetradecanoylphorbol-13-acetate or epidermal growth factor. Together, TGF-beta 1 and epidermal growth factor produce a greater stimulation of soft agar growth than either growth factor alone. In contrast, addition of TGF-beta 1 and 12-O tetradecanoylphorbol-13-acetate together does not stimulate soft agar growth beyond that produced by TGF-beta 1 alone. Interestingly, retinoic acid inhibits the ability of all three factors to induce the anchorage-independent growth of Cl 40 cells. TGF-beta also exerts long-term effects on Cl 41 cells. This was determined by isolating TGF-beta-induced soft agar colonies and examining their dependence on TGF-beta. Five of the six anchorage-independent clones isolated after TGF-beta 1 treatment were found to exhibit anchorage-independent growth in the absence of TGF-beta. In addition, these clones respond far more strongly to TGF-beta 1 than do the parental Cl 41 cells in terms of both the numbers and the sizes of colonies formed in soft agar. The findings reported here are compatible with the proposal that TGF-beta mediates some effects of 12-O tetradecanoylphorbol-13-acetate. PMID- 1933859 TI - Importance of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vivo. AB - We have elucidated the importance of a transforming growth factor (TGF) alpha and epidermal growth factor receptor autocrine mechanism on the growth of a human ovarian serous cystadenocarcinoma-derived cell line (SHIN-3) in vitro. In this study, we studied the biological significance of this autocrine mechanism in vivo using female athymic nude (nu/nu) mice. We measured the mouse plasma epidermal growth factor and TGF alpha levels by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Plasma epidermal growth factor concentrations were remarkably decreased by sialoadenectomy (Sx): 410 +/- 65 (SE) pg/ml (n = 10) in intact animals; and undetectable in Sx mice (n = 5). Plasma TGF alpha levels were 90 and 40 pg/ml in intact and in Sx animals, respectively. Ten million SHIN 3 cells inoculated into nu/nu mice formed tumors in 100% of mice, and tumors grew progressively. Implantabilities and tumor growth rates of inoculated cells were not affected by Sx and even by Sx and anti-mouse epidermal growth factor antibody treatment. However, anti-TGF alpha monoclonal antibody (mAb) administered to SHIN 3 cell-inoculated Sx animals drastically reduced the tumor growth. Although 10(7) SHIN-3 cells formed tumors in this group, tumor growth was significantly inhibited by 10 micrograms of anti-TGF alpha mAb given 3 times a week, and growth inhibitions were more by 20 micrograms of anti-TGF alpha mAb. Moreover, as aggressive tumor growth as that in Sx animals was resumed by the cessation of anti-TGF alpha mAb treatments. All these data suggested the biological importance of a TGF alpha/epidermal growth factor receptor autocrine mechanism on the growth of this cell line in vivo. PMID- 1933860 TI - Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen positive patients. AB - We describe a method to postlabel, in vivo, biotinylated monoclonal antibodies pretargeted onto tumor deposits when most of the non-tumor-bound antibodies have already been cleared as avidin-bound complexes. The application of this principle to tumor detection by immunoscintigraphy was tested in 20 patients with histologically documented cancer and increased circulating carcinoembryonic antigen levels. One mg of biotinylated anti-carcinoembryonic antigen monoclonal antibody (FO23C5) was administered i.v. (first step). After 3 days, 4-6 mg of cold avidin were injected i.v. (second step), followed 48 h later by 0.2-0.3 mg of a biotin derivative labeled with 111In (2-3 mCi) (third step). No evidence of toxicity was observed. Whole body radioactivity distribution was measured in five patients at various intervals postinjection by the conjugate counting technique. Tumors and metastases were detected in 18 of 19 patients (the remaining patient was a true negative) within 3 h after administration of 111In-biotin by planar or single photon emission tomography imaging. At the time of imaging, tumor/blood pool ratio was 5.5 +/- 3.2, and tumor/liver ratio was 6.7 +/- 3.9. Blood clearance of 111In-biotin was multiexponential, with the fast component having a t1/2 of 5 +/- 3 min. Urinary excretion of radioactivity over 3 h was 63.5 +/- 4.9% of the injected dose. Radioactivity at 3 h was 6.5 +/- 1.8% in blood, 1.6 +/ 0.3% in the kidney, and 2.4 +/- 0.6% in the liver. This approach represents an improvement in immunoscintigraphic techniques for tumor localization. The potential use for radioimmunotherapy is discussed. PMID- 1933861 TI - Expression of mutant p53 in melanoma. AB - Mutant p53 has been noted in a variety of human malignancies including carcinomas of lung, breast, and colon, which have also been reported to have frequent karyotype anomalies involving the locus of the p53 gene (17p13). Whereas chromosomal abnormalities of chromosomes 1, 6, and 7 have been noted previously in melanoma, frequent aberrations in chromosome 17 have not been reported previously. Due to the common mutation of this locus in so many types of neoplasms, a range of melanomas from different stages of tumor progression were examined immunohistochemically for expression of mutant p53, in order to assess its prevalence and consider the role of this oncogene in the biological progression of melanoma. Forty-five of 53 (85%) specimens from a range of primary and metastatic melanomas were found to have detectable evidence of p53 gene mutation, by virtue of the immunohistochemical detection of mutant p53 protein. Significantly increased prevalence of mutant p53 was found in metastatic melanoma, compared with primary tumors (P less than 0.05). These findings represent one of the highest incidences of this oncogenic mutation yet recorded in a human malignancy and support the concept that p53 may have a functional role in development of the metastatic tumor phenotype. PMID- 1933862 TI - Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells. AB - The mode of cell death of two strains of mouse lymphoma L5178Y cells was studied following photodynamic therapy (PDT) sensitized by chloroaluminum phthalocyanine. Strains LY-R and LY-S differ in their relative sensitivities to UVC radiation, X radiation, and PDT; both responded to PDT by undergoing apoptosis. The DNA was degraded into fragments with lengths which are multiples of approximately 180-190 base pairs (i.e., oligonucleosome size), a biochemical marker of apoptosis. The DNA fragmentation was dose and time dependent which indicates this response to be an enzymic process related to cell killing. Cycloheximide, a protein synthesis inhibitor, and actinomycin D, an RNA synthesis inhibitor, enhanced the endonucleolytic DNA fragmentation. Transmission electron microscopy revealed chromatin condensation around the periphery of the nucleus, which is also characteristic of apoptosis. The induction of apoptosis in L5178Y cells by PDT was rapid, with marked degradation of DNA occurring in as little as 30 min. The rapidity of the response to PDT suggests that cellular damage produced by PDT can directly activate endonucleolysis and chromatin condensation, thereby by-passing many of the early steps in the signal transduction program which are acted upon by other agents causing apoptosis. PMID- 1933863 TI - V(D)J recombinase-like activity mediates hprt gene deletion in human fetal T lymphocytes. AB - Studies from several laboratories worldwide have developed a large database for in vivo hypoxanthine-guanine phosphoribosyltransferase gene mutations in human T lymphocytes. Sufficient differences have been found thus far between the spectrum for spontaneous mutations in adults and that observed in the fetus to suggest fundamental differences in in vivo mutagenic mechanisms at these two life stages. In adults, only approximately 15% of hypoxanthine-guanine phosphoribosyltransferase mutations have structural alterations on Southern blots, while in the fetus 75% of mutations show alterations of which one-half are deletions of exons 2 and 3. We have now sequenced the breakpoint sites for these specific deletions in 18 mutant lymphocyte clones isolated from 13 normal newborns. Three classes of deletions were found. Each class had the same intron 1 breakpoint but a different intron 3 breakpoint. These mutations have all the signatures of a V(D)J recombinase-mediated event (a 5' consensus heptamer, 3' consensus heptamer and nonamer, nibbling, non-germline-encoded nucleotides, P nucleotides). At the 3' breakpoint of the most common class (comprising 83% of the mutants) a perfect heptamer can be created by postulating a hairpin loop which could attain a Z-DNA configuration. This feature may indicate recombinase preference for certain DNA structures. These results implicate the V(D)J recombinase in illegitimate events causing mutation in this housekeeping gene during T-cell development. Inactivation of genes involved in the control of growth and differentiation (e.g., tumor suppressor genes) by this mechanism may have important implications for cancer development. PMID- 1933864 TI - Down-regulation of cdc2 in senescent human and hamster cells. AB - Senescent cells fail to respond to serum-induced signals for DNA synthesis. Because a central role for the p34cdc2 protein kinase is postulated in control of the cell cycle, we examined the status of this kinase in senescent cells and other growth-arrested cells. In growing human and Syrian hamster fibroblasts, three 35S-labeled proteins of 34-36 kDa were immunoprecipitated with p34cdc2 antiserum. Only the two slower migrating forms were phosphorylated as determined by 32P labelling. In senescent cells, which failed to incorporate [3H]thymidine, no p34cdc2 protein was synthesized and very little or no cdc2 mRNA was observed. When maintained for 48 h in 0.5% serum, young cells also retained only marginal cdc2 expression. After stimulation of low serum-arrested cells by addition of 10% serum, a time-dependent increase of cdc2 mRNA was observed, whereas serum stimulation of senescent cells did not increase cdc2 mRNA. In contrast to senescent and low serum-arrested cells, cdc2 mRNA was expressed at normal levels in cells partially growth arrested by isoleucine deficiency in G1, by aphidicolin at G1-S, by etoposide in G2, or by Colcemid in the M phase of the cell cycle, indicating that cdc2 down-regulation does not always occur upon growth arrest. Following transfection of a plasmid containing the human CDC2 gene into hamster cells, expression of human cdc2 failed to overcome the block to DNA synthesis in senescent cells. Although p34cdc2 was synthesized in the transfected cells, the multiple phosphorylated forms of the proteins were not observed. Taken together, these data support the concept that a chain of events leads to senescence. While p34cdc2 kinase may be one of the critical elements, other cell cycle controls are also involved. PMID- 1933865 TI - Cytotoxic effect of cis-parinaric acid in cultured malignant cells. AB - Parinaric acid, a naturally occurring 18-carbon fatty acid containing 4 conjugated double bonds, is toxic to human monocytic leukemia cells at concentrations of 5 microM or less. Conditioning of the medium reduces the cytotoxic effect, suggesting that parinaric acid and not a metabolite is the active agent. The mechanism of parinaric acid toxicity appears to involve lipid peroxidation because the toxic action can be blocked by the addition of butylated hydroxytoluene. When U-937 cells are differentiated to the monocytic form, they become resistant to as much as 30 microM parinaric acid. This difference in sensitivity may be explained in part by the fact that the undifferentiated cells take up 3 to 4 times more parinaric acid. Concentrations of parinaric acid less than 5 microM are also toxic to human THP-1 monocytic leukemia, HL-60 human promyelocytic leukemia, and Y-79 human retinoblastoma cells. Measurements of protein synthesis indicate that differentiated U-937 cells, confluent cultures of human fibroblasts, bovine aortic endothelial cells, and CaCo-2 colonic mucosal cells are much less sensitive to parinaric acid than the malignant cell lines tested, suggesting that the cytotoxic action may be selective for rapidly growing malignant tumors. Thus, parinaric acid may be the prototype of a new class of lipid chemotherapeutic agents that contain a conjugated system of double bonds and act by sensitizing tumor cells to peroxidation. PMID- 1933866 TI - Glucocorticoid growth suppression response in 13762NF adenocarcinoma-derived Con8 rat mammary tumor cells is mediated by dominant trans-acting factors. AB - The in vitro and in vivo growth of Con8 cells, a single cell-derived subclone of the 13762NF-transplantable rat mammary adenocarcinoma, is strongly suppressed by glucocorticoid hormones. Hybrids were formed between glucocorticoid-suppressible Con8.hD6 mammary tumor cells (Con8 transfected with the histidinol dehydrogenase selectable marker) and either glucocorticoid-resistant 8RUV7 mammary tumor cells (derived from Con8) or MCT-HTC rat hepatoma cells. Both of the glucocorticoid resistant 8RUV7 and MCT-HTC fusion partners express functional glucocorticoid receptors, since hormone-responsive genes such as plasminogen activator inhibitor are fully dexamethasone inducible. Karyotypic analyses revealed that the hybrid cell populations possessed the appropriate number of chromosomes for a fusion between the glucocorticoid-suppressible and either of the two resistant cell types. Moreover, Northern blots showed that the intertissue hybrids expressed transcripts for both the milk fat globule membrane protein gene originating from the parental Con8.hD6 mammary tumor cells as well as mouse mammary tumor virus glycoprotein sequences which had been transfected into the MCT-HTC hepatoma cells as a molecular tag. Analysis of DNA content and [3H]thymidine incorporation demonstrated that growth of both the intratissue (Con8.hD6 x 8RUV7) and intertissue (Con8.hD6 x MCT-HTC) hybrids was glucocorticoid suppressible, even though the absolute rates of proliferation differed depending on the parental cells. Analysis of conditioned medium isolated from glucocorticoid-treated and untreated Con8.hD6 cells indicated that the growth suppression response is not mediated through the elaboration of an extracellular growth inhibitor. Taken together, our results demonstrate that the glucocorticoid-suppressible phenotype of Con8 rat mammary tumor cells is dominant, suggesting the existence of intracellular regulatory factors under glucocorticoid control that may function as trans-acting suppressors of tumor cell growth. PMID- 1933867 TI - Human high molecular weight-melanoma associated antigen mimicry by an anti idiotypic antibody: characterization of the immunogenicity and the immune response to the mouse monoclonal antibody IMel-1. AB - The mouse anti-idiotype (anti-id) monoclonal antibody (mAb) IMel-1 recognizes an idiotope in the antigen combining site of the immunizing anti-human high molecular weight melanoma-associated antigen (HMW-MAA) mAb 225.28. The mAb IMel-1 is able to induce an immune response against self cross-reacting HMW-MAA in rabbits that express HMW-MAA in normal tissues. Most of the rabbit anti-anti-id antibodies recognize a spatially distant determinant(s) from that defined by anti HMW-MAA mAb 225.28. The immunogenicity of mAb IMel-1 is enhanced by its administration with the muramyl dipeptide-derived adjuvant. Anti-HMW-MAA antibodies were not detected in sera from rabbits immunized with HMW-MAA bearing cultured human melanoma cells. The differential immunogenicity of mAb IMel-1 and cell membrane bound HMW-MAA may account for the ability of anti-id mAb to induce anti-HMW-MAA immunity in patients who have not mounted such a response to HMW-MAA present in their lesions. Rabbit anti-HMW-MAA antibodies induced by anti-id mAb IMel-1 inhibited interactions of melanoma cells with elements of extracellular matrix. This may represent an additional mechanism by which anti-HMW-MAA immunity may affect the biology of melanoma cells in patients with melanoma immunized with anti-id mAb IMel-1. PMID- 1933868 TI - Cytochrome P-450-mediated activation and irreversible binding of the antiestrogen tamoxifen to proteins in rat and human liver: possible involvement of flavin containing monooxygenases in tamoxifen activation. AB - Tamoxifen (TXF), a triphenylethylene antiestrogen, is the major therapeutic agent for breast cancer. In rare cases, TXF treatment appears to increase incidence of endometrial cancer. Also in rats, TXF was found to induce hepatocellular carcinoma. Previous studies suggested that metabolism of TXF may contribute to its antiestrogenic and anticancer activity. The current study demonstrates a novel route of TXF metabolism. TXF is metabolized by rat and human liver microsomes into a reactive intermediate (txf*) which binds irreversibly to microsomal proteins. The binding requires NADPH and O2 and is inhibited by CO, inhibitors of P-450, and antibodies to rat NADPH-P450 reductase, indicating catalysis by P450. Phenobarbital treatment of rats markedly increases binding, suggesting the involvement of induced P450s. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of proteins from incubation of [14C] TXF with phenobarbital-treated microsomes exhibits a major radiolabeled zone which corresponds to a molecular weight of approximately 54,000, suggesting binding to a P-450. Cysteine and glutathione inhibited the binding of TXF without significantly affecting P-450-mediated metabolism of TXF, possibly by reacting with txf* or by competing for the same binding sites. Exposure of phenobarbital treated microsomes and control-microsomes to 50 degrees C for 90 s, which inactivates the flavin-containing monooxygenase (FMO), diminished binding and pH 8.6 enhanced binding. Also, alternate FMO substrates inhibited binding. These findings indicate that P-450 and possibly FMO catalyze the reactions leading to the formation of txf*. However, incubations with single-labeled and dual radiolabeled tamoxifen or with [14C]TXF-N-oxide demonstrated that monodesmethyl TXF and TXF-N-oxide, the principal P-450 and FMO-mediated metabolites, respectively, are not on the major route of txf* formation, indicating that txf* could not be an aldehyde derived from tamoxifen nitrone. Thus, though the structure of txf* was not characterized, certain possibilities were excluded. Speculations on the structure of txf* and on its possible pharmacological and toxicological activity are presented. PMID- 1933869 TI - Phase I study of thiotepa in combination with the glutathione transferase inhibitor ethacrynic acid. AB - The glutathione transferases comprise a family of isoenzymes, one or more of which are involved in the conjugation of alkylating agents to glutathione (GSH). Increased GSH transferase activity has been shown to underlie acquired resistance to several alkylating agents. Ethacrynic acid inhibits the isoenzymes of GSH transferase with 50% inhibitory concentration values ranging from 0.3 to 6.0 microM and has been shown to restore sensitivity to alkylating agents in drug resistant animal tumor models. We entered 27 previously treated patients with advanced cancer on a study of ethacrynic acid (25 to 75 mg/m2 p.o. every 6 h for 3 doses) and thiotepa (30 to 55 mg/m2 i.v. 1 h after the second dose of ethacrynic acid). The major toxicity of ethacrynic acid was diuresis, which was observed at every dose level; in addition, severe metabolic abnormalities occurred at 75 mg/m2. At 50 mg/m2, the diuretic effects were manageable. Myelosuppression was the most important effect of the combination. Two of seven courses of ethacrynic acid, 50 mg/m2, and thiotepa, 55 mg/m2, were associated with grade 3 or 4 neutropenia and/or thrombocytopenia. Nausea/vomiting greater than or equal to grade 2 was observed in 16% of courses. GSH transferase activity was assayed spectrophotometrically in the peripheral mononuclear cells of all patients. At each dose level, activity decreased following ethacrynic acid administration, with recovery by 6 h. Administration of ethacrynic acid, 50 mg/m2, resulted in a mean nadir of transferase activity of 37% of control. The pharmacokinetics of thiotepa and its principal metabolite TEPA were studied in 23 patients. The plasma disappearance of thiotepa fit a two-compartment open model with a terminal half-life of approximately 2 h. Plasma TEPA levels peaked at a mean of 2.16 h following thiotepa administration. The harmonic mean terminal half life of TEPA was 10.4 h, and the TEPA area under the curve (AUC) did not increase with increasing thiotepa dose. The AUC of thiotepa was approximately twice, and the clearance about one-half, of the values obtained in a previous study of single agent thiotepa. The AUC of TEPA was lower than that previously observed. The data suggest that ethacrynic acid inhibits enzymes involved in the metabolic disposition of thiotepa, including its oxidative desulfuration to TEPA. The severity of the platelet toxicity was correlated with the AUC of thiotepa, but not with that of TEPA. This combination of thiotepa and ethacrynic acid will be tested further in Phase II trials. PMID- 1933870 TI - Ascorbic acid enhances the effects of 6-hydroxydopamine and H2O2 on iron dependent DNA strand breaks and related processes in the neuroblastoma cell line SK-N-SH. AB - Neuroblastoma cells accumulate ascorbic acid and iron. It was hypothesized that these features could be exploited for sensitizing neuroblastoma cells for therapy in combination with reactive oxygen intermediates. In the present study the effects of 6-hydroxydopamine (6-OHDA) and H2O2 on metabolic parameters critical for cell survival were investigated in cells with low and high ferritin content in the presence and absence of ascorbate. Human neuroblastoma SK-N-SH cells were pretreated with 100 microM FeSO4 and 10 microM desferrioxamine, respectively, for 24 h yielding cells with different ferritin contents. The effects of 6-OHDA and H2O2 (25 microM-250 microM) in the absence and presence of 1 mM ascorbic acid on DNA strand break formation, activation of poly(ADP-ribose) polymerase, and finally decrease in NAD+ and ATP concentration were investigated. All these parameters were influenced by 6-OHDA and H2O2 in a concentration-dependent manner in a similar way. The effects were most pronounced in ferritin-rich cells and in the presence of ascorbic acid. Using isolated CCC PM2 DNA, 6-OHDA and ascorbic acid caused strand breaks that were prevented in the presence of mannitol or desferrithiocine. H2O2-mediated strand breaks were observed only in the presence of ascorbic acid. Based on these data and data published by others a model explaining the deleterious effects of ascorbic acid on neuroblastoma cells is presented. It is suggested that continuous application of a high dosage of ascorbic acid might be a useful approach in neuroblastoma therapy. PMID- 1933871 TI - Intrathecal 6-mercaptopurine: preclinical pharmacology, phase I/II trial, and pharmacokinetic study. AB - For over 30 years, oral 6-mercaptopurine (6-MP) has been a mainstay of systemic maintenance therapy for acute lymphoblastic leukemia. Despite its efficacy as an antileukemic agent, 6-MP has not been previously administered by the intrathecal (IT) route. In anticipation of a clinical trial of IT 6-MP, preclinical cytotoxicity and pharmacology studies were performed to define a safe, effective dose. The optimal concentration (greater than 1 microM) and duration of exposure (greater than 12 h) to 6-MP required for cytotoxicity were determined in vitro using human leukemia cell lines. The dose required to achieve the desired cerebrospinal fluid concentrations in humans was derived from pharmacokinetic parameters determined in rhesus monkeys. A phase I/II study was then performed in pediatric patients with refractory meningeal leukemia. Nine patients (aged 3.5 to 16 years) with chronic meningeal leukemia (2 to 6 central nervous system relapses) were entered onto the study. All had previously failed, at a minimum, IT methotrexate, IT cytarabine, and cranial (+/- spinal) radiation. A 10-mg IT dose of 6-MP (calculated to produce cytotoxic cerebrospinal fluid levels for 12 h) was administered twice weekly for 4 weeks. There were four complete responses and three partial responses. The duration of complete responses ranged from 7 to 22 weeks. Observed toxicities were not dose limiting and included mild headache (three patients) and minimal nausea (two patients). Pharmacokinetic studies performed in patients confirmed that cerebrospinal fluid concentrations of 6-MP were greater than 1 microM for 12 h. These results indicate that the IT administration of 6-MP is feasible, is not associated with significant toxicity, and has definite activity in patients with refractory meningeal leukemia. PMID- 1933872 TI - Follow-up study of twenty-four families with Li-Fraumeni syndrome. AB - The Li-Fraumeni cancer family syndrome is manifested by susceptibility to breast cancer, sarcomas, and other neoplasms in children and young adults. The present study utilized clinical follow-up data on 545 members of 24 Li-Fraumeni kindreds living and cancer-free at family ascertainment. Two hypotheses were tested based on a model of autosomal dominant genetic predisposition: (a) that syndrome cancers would continue to occur excessively during follow-up compared to the general population, and (b) that the tumors would occur primarily among those family members likely to carry the gene. Population cancer rates were compared with cancer rates in follow-up of the cohort from ascertainment to 1988. Risk of carrying the gene for the syndrome at the time of ascertainment was calculated for each family member under two models with somewhat different definitions of affection with the syndrome. Cancer occurrence after ascertainment was then analyzed according to the risks. Cancer did continue to occur excessively among the entire cohort during follow-up [relative risk (RR 2.1)]. The excess was greatest below age 20 (RR 21.1), declined with increasing age, and was most pronounced for neoplasms featured in the syndrome (RR 18.2). Among persons less than age 45, at least 87% of cancers occurred in those at higher risk of carrying the gene under both genetic models (RR 22.9 and 21.3). The clinical data, therefore, reliably identify individuals likely to carry a dominantly inherited gene conferring susceptibility to a specific constellation of neoplasms. Recent identification of a germ line mutation in the tumor suppressor gene p53 in persons with the syndrome may, if confirmed, have implications for ultimately defining the component tumors of the syndrome and for the causes and prevention of those tumors arising outside these families. PMID- 1933873 TI - Oxygenation of carcinomas of the uterine cervix: evaluation by computerized O2 tension measurements. AB - Direct oxygen partial pressure (pO2) readings in cancers of the cervix and in the normal cervix of nulliparous or parous women were obtained using a computerized pO2 histography system. The oxygenation status of the tumors was evaluated as a function of clinical staging and histological grading. pO2 measurements were performed with a customized electrode system in conscious pre- and postmenopausal, untreated patients with well-defined arterial blood gas status. With this technique, pO2 measurements in the normal cervix of nulliparous women resulted in oxygenation patterns which were characteristic for normal, adequately supplied tissues (median pO2, 48 mm Hg) with approximately 1% of the pO2 values grouped between zero and 2.5 mm Hg, i.e., in a range with less than half-maximum radiosensitivity. As a rule, the mean (and median) pO2 values were distinctly lower in the normal cervix of parous women (most probably due to scar formation following vaginal delivery) and in malignancies. In the normal cervix of parous women the median pO2 value was 13 mm Hg (with approximately 14% of the pO2 readings in the lowest class), 14 mm Hg in International Federation of Gynecologists and Obstetricians I/II tumors (2% of the readings in the lowest pO2 class), and 11 mm Hg in International Federation of Gynecologists and Obstetricians III/IV cancers (1% of the pO2 data in the lowest class). To date, 5 of 18 cervical cancers exhibited pO2 values between zero and 2.5 mm Hg. The oxygenation pattern in cervical cancers and the occurrence of hypoxia and/or anoxia did not correlate with either the clinical stages and histological grades or with a series of clinically relevant parameters (e.g., tumor size). No significant differences were found between pre- and postmenopausal tumors, between squamous cell carcinomas and adenocarcinomas, and between endophytic or exophytic tumors. From these studies there is clear indication that the oxygenation status of individual tumors cannot be predicted on the basis of staging and/or grading, predominantly because of the pronounced tumor-to-tumor variabilities. Evaluation of the tissue oxygenation of individual tumors is thus mandatory to prove that tumor oxygenation can predict the overall prognosis and/or treatment outcome. PMID- 1933874 TI - Mammary cancer prevention by conjugated dienoic derivative of linoleic acid. AB - Conjugated dienoic derivative of linoleic acid (CLA) is a collective term which refers to a mixture of positional and geometric isomers of linoleic acid. It is a naturally occurring substance in food and is present at higher concentrations in products from animal sources. The present study reports that synthetically prepared CLA is an effective agent in inhibiting the development of mammary tumors induced by dimethylbenz(a)anthracene. Rats were fed either the AIN-76A basal diet or the same diet supplemented with 0.5, 1, or 1.5% CLA by weight. These diets were started 2 weeks before carcinogen administration and continued until the end of the experiment. The total number of mammary adenocarcinomas in the 0.5, 1, and 1.5% CLA groups was reduced by 32, 56, and 60%, respectively. The final tumor incidence and cumulative tumor weight were similarly diminished in rats fed the CLA-containing diets. In general, there appeared to be a dose dependent protection at levels of 1% CLA and below, but no further beneficial effect was evident at levels above 1%. Chronic feeding of up to 1.5% CLA produced no adverse consequences in the animals. Analysis of the phospholipid fraction from liver and mammary tumor extracts showed that only the c9,t11 isomer of CLA was incorporated and that the level of incorporation increased with dietary intake. An interesting property of CLA is its ability to suppress peroxide formation from unsaturated fatty acid in a test-tube model (Cancer Res., Ha et al. 50: 1097-1101, 1990). In view of this information, the amount of thiobarbituric acid-reactive substances (lipid peroxidation products) present endogenously in liver and mammary gland was quantitated. The feeding of CLA (for either 1 or 6 months) resulted in a decrease in the extent of lipid peroxidation in the mammary gland, but such a suppressive effect was not detected in the liver. It should be noted that maximal antioxidant activity was observed with only 0.25% CLA in the diet, whereas maximal tumor inhibition was achieved at about 1% CLA. Hence there is a discrepancy between the antioxidant efficacy of CLA and its anticarcinogenic potency, suggesting that some other mechanisms might be involved in cancer protection. Unlike the stimulatory effect of linoleic acid in carcinogenesis (Cancer Res., Ip et al., 45: 1997-2001, 1985), the reaction of CLA in cancer prevention is specific, and CLA is more powerful than any other fatty acid in modulating tumor development. PMID- 1933875 TI - Morphological transformation and DNA adduct formation by benz[j]aceanthrylene and its metabolites in C3H10T1/2CL8 cells: evidence for both cyclopenta-ring and bay region metabolic activation pathways. AB - Benz[j]aceanthrylene (B[j]A), a cyclopenta-fused polycyclic aromatic hydrocarbon related to 3-methylcholanthrene, has been studied to identify the major routes of metabolic activation in transformable C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts in culture. Previous studies have reported that the major (55% of total) B[j]A metabolite formed by C3H10T1/2 cells was (+/-)-trans-9,10-dihydro 9,10-dihydroxy-B[j]A (B[j]A-9,10-diol), the dihydrodiol in the bay-region ring, with moderate amounts (14% of total) of (+/-)-trans-1,2-dihydro-1,2-dihydroxy B[j]A (B[j]A-1,2-diol), the cyclopenta-ring dihydrodiol. The morphological transforming activities of three potential intermediates formed by metabolism of B[j]A by C3H10T1/2 cells, (+/-)-anti-trans-9,10-dihydro-9,10-dihydroxy-B[j]A-7,8 oxide (B[j]A-diol-epoxide), B[j]A-9,10-oxide, and B[j]A-1,2-oxide as well as the two B[j]A-dihydrodiols were examined. B[j]A, B[j]A-diol-epoxide, B[j]A-1,2-oxide, and B[j]A-9,10-diol were found to have moderate to strong activities with B[j]A diol-epoxide the most active compared to B[j]A, while B[j]A-1,2-diol was inactive. B[j]A-9,10-oxide was found to be a weak transforming agent. At 0.5 microgram/ml, the following percentage of dishes with type II or III foci were observed: B[j]A, 59%; B[j]A-diol-epoxide, 75%; B[j]A-1,2-oxide, 25%; and B[j]A 9,10-diol, 17%. DNA adducts of B[j]A, B[j]A-9,10-diol, B[j]A-diol-epoxide, B[j]A 9,10-oxide, and B[j]A-1,2-oxide in C3H10T1/2 cells were isolated, separated, identified, and quantitated using the 32P-postlabeling method. B[j]A forms two major groups of adducts: one group of adducts is the result of the interaction of B[j]A-1,2-oxide with 2'-deoxyguanosine and 2'-deoxyadenosine; the second group of adducts is a result of the interaction of B[j]A-diol-epoxide with 2' deoxyguanosine and 2'-deoxyadenosine. Qualitative and quantitative analysis of the postlabeling data suggests that B[j]A is metabolically activated by two distinct routes, the bay-region diol-epoxide route and the cyclopenta-ring oxide route, the former being the most significant. PMID- 1933876 TI - Enhanced tumorigenesis of NR6 cells which express non-down-regulating epidermal growth factor receptors. AB - Sequences in the regulatory carboxyl terminus of the epidermal growth factor (EGF) receptor are required for ligand-induced internalization via a high affinity saturable endocytic pathway and for receptor down-regulation. To investigate the role of down-regulation in attenuating mitogenic signals, we compared the ability of NR6 cells expressing holo and mutant down-regulation defective EGF receptors to form tumors in athymic mice. NR6 cells expressing mutant EGF receptors reproducibly formed rapidly growing tumors, whereas cells expressing holo EGF receptors had a low tumorigenic potential. Serial passage of tumors of NR6 cells expressing mutant EGF receptors resulted in an enhanced rate of tumor formation that directly correlated with increased expression of mutant receptors. Tumor growth was inhibited by a competitive antagonist anti-EGF receptor monoclonal antibody. Excessive signaling from the cell surface can result from lack of sequences required for endocytosis and from saturation of endocytic mechanisms. Non-down-regulating kinase-active EGF receptors provide an especially strong growth signal, manifested as rapid tumor growth in athymic mice. PMID- 1933877 TI - Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens. AB - In lung and liver cancers, p53 mutations are mostly G:C to T:A transversions. This type of mutation is known to be induced by benzo(a)pyrene and aflatoxin B1 which are associated with the etiology of lung and liver cancers, respectively. Using a novel assay based on DNA polymerase fingerprint analysis, we identified p53 nucleotides targeted by these carcinogens. Thirteen of 14 nucleotide residues of the p53 gene which underwent G:C to T:A mutations in lung cancers were targeted by benzo(a)pyrene. Similarly, aflatoxin B1 formed adducts at a mutational hotspot specific for liver cancer. The same nucleotide (third base of codon 249), which mutates rarely in lung cancers, was not a target for benzo(a)pyrene. These in vitro observations indicate that p53 mutational hotspots identified in different tumors are selected targets specifically for the etiologically defined environmental carcinogens. PMID- 1933878 TI - Inhibition of ribonucleotide reductase by gallium in murine leukemic L1210 cells. AB - Our previous studies of the mechanism of cell growth inhibition by gallium have suggested that the block in cellular iron uptake induced by transferrin-gallium results in an inhibition of the iron-dependent M2 subunit of ribonucleotide reductase. However, it is not known whether the inhibitory effect of gallium on ribonucleotide reductase is solely the result of limiting iron availability for enzyme activity or whether a direct effect of intracellular gallium on the enzyme is also involved. In the present study, utilizing a cell-free assay, we show that gallium nitrate directly inhibits CDP and ADP reductase activity. Inhibition of DNA synthesis by gallium nitrate thus appears to be due to a combination of a block in iron availability to ribonucleotide reductase and a direct inhibition of the enzyme by gallium. PMID- 1933880 TI - Correspondence Re: Michiel M. Van Lookeren Campagne et al., 8-chloroadenosine 3',5'-monophosphate inhibits the growth of Chinese hamster ovary and molt-4 cells through its adenosine metabolite. Cancer Res., 51: 1600-1605, 1991. PMID- 1933879 TI - p53 mutations in nonastrocytic human brain tumors. AB - Genomic DNA from 51 primary human brain tumors was screened for the presence of mutations in the tumor suppressor gene, p53, using the polymerase chain reaction and single strand conformation polymorphism analysis, followed by direct DNA sequencing. Mutations leading to an amino acid change were found in 2 of 17 (12%) oligodendrogliomas and 2 of 19 (11%) medulloblastomas but none of 15 ependymomas. Sites of mutations were in exon 5 (codon 141), exon 6 (codon 193 and 213), and exon 7 (codon 246). In addition, there were silent mutations in exon 6 (codon 213) in one oligodendroglioma and in one ependymoma. This study points to the possible role of the p53 tumor suppressor gene in some central nervous system neoplasms of divergent histogenesis. PMID- 1933881 TI - Carcinogenesis and cancer: different perspectives on the same disease. PMID- 1933882 TI - Modulation by butylated hydroxytoluene of liver and bladder carcinogenesis induced by chronic low-level exposure to 2-acetylaminofluorene. AB - The modulating effect of five dose levels of butylated hydroxytoluene (BHT) on liver and bladder carcinogenesis induced in rats by concurrent exposure to 2 acetylaminofluorene (AAF) was investigated. AAF at a low dose of 50 ppm was fed simultaneously with concentrations of 100, 300, 1000, 3000, or 6000 ppm BHT in the diet to male F344 rats for up to 76 weeks. By 12 weeks, AAF alone induced altered hepatocellular foci, identified by iron storage deficiency and gamma glutamyltranspeptidase activity. At subsequent time points of 24, 36, and 48 weeks, the number of foci progressively increased, and at the end of the study, the incidence of liver neoplasms was 100%, a new finding with such a low dose of AAF. Simultaneous feeding of BHT inhibited the induction of liver altered foci by AAF in a dose-related manner and reduced the incidence of hepatocellular carcinomas and the number of liver neoplasms per animal. Feeding of 6000 ppm BHT, but not of lower doses, together with AAF resulted in an increase in the incidence and multiplicity of bladder neoplasms, and 3000 ppm increased nodular hyperplasia of the bladder. These results suggest that the chemoprevention by BHT of cancer resulting from low-level long-term carcinogen exposure may be achieved at doses that do not produce adverse effects. PMID- 1933883 TI - Immunological quantitation of levels of tissue inhibitor of metalloproteinase-1 in human colon cancer. AB - Treatment of rodent cells with the tumor promoter 12-O-tetradecanoylphorbol-13 acetate activates protein kinase C, leading to increased expression of several genes, including a gene originally designated TPA-S1 or phorbin (M. D. Johnson, G. M. Housey, P. T. Kirschmeier, and I. B. Weinstein, Mol. Cell Biol., 7: 2821 2829, 1987). Sequence analysis of this cloned gene indicated homology with human erythroid-potentiating activity and tissue inhibitor of metalloproteinase (TIMP 1). Elevated levels of phorbin mRNA have been observed in human colon tumors (J. G. Guillem, M. F. Levey, L. L. Hsieh, M. D. Johnson, P. LoGerfo, K. A. Forde, and I. B. Weinstein, Mol. Carcinogen., 3: 68-74, 1990) and this increase correlated with the extent of invasion. To further investigate this phenomenon at the protein level, monoclonal antibodies were developed against the recombinant form of TIMP-1. A competitive enzyme-linked immunosorbent assay was developed for quantitation of the TIMP-1 protein in tissue extracts. Elevated levels of TIMP-1 protein were found in 31 human colon tumors, compared to paired samples of adjacent normal mucosa. In a subset of samples, previously analyzed for phorbin mRNA levels (n = 25), there was a good correlation between the abundance of TIMP 1 protein and phorbin mRNA. Immunoaffinity column purification of tumor extracts followed by Western blot analysis was used to confirm the enzyme-linked immunosorbent assay data. These results provide evidence that phorbin and TIMP-1 represent the same gene. In addition, the immunoassays we have developed may be useful in further studies on the role of TIMP-1 in human colon cancer. PMID- 1933884 TI - Differential binding and biological activities of epidermal growth factor and transforming growth factor alpha in a human pancreatic cancer cell line. AB - The binding characteristics and biological activities of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) were studied in T3M4 human pancreatic cancer cells. Scatchard analysis of 125I-EGF binding data at pH 7.4 indicated the presence of two orders of binding sites: a high-affinity site (Kd = 0.58 nM; 25,300 sites/cell) and a low-affinity site (Kd = 7.0 nM; 484,000 sites/cell). At pH 8.5, there was a decrease in the number of high-affinity sites. In contrast, only a single order of high-affinity sites was detected with 125I-TGF-alpha at either pH 7.4 (Kd = 0.57 nM; 100,200 sites/cell) or pH 8.5 (Kd = 0.70 nM; 230,400 sites/cell). The two ligands bound to the same receptor, as determined in cross-linking experiments and in competitive binding assays performed in the presence of an anti-EGF receptor antibody that allows for EGF binding. Phosphoamino acid analysis of the immunoprecipitated EGF receptor indicated that EGF exerted a greater effect than TGF-alpha on tyrosine phosphorylation of the receptor. EGF and TGF-alpha also exhibited different potencies with respect to their effects on inositol 1,4,5-trisphosphate generation and exerted divergent effects on the kinetics of inositol 1,4,5 trisphosphate formation. These findings point to dissimilar interactions of EGF and TGF-alpha with the EGF receptor in T3M4 cells, which may lead to differential activation of signal transduction pathways by these ligands. PMID- 1933885 TI - Predictive value of interleukin-6 and neopterin in patients with multiple myeloma. AB - Concentrations of interleukin-6 and neopterin were measured in sera from 44 patients with multiple myeloma. To judge the relative prognostic value of these analyses, other clinical and laboratory variables were concomitantly determined. The patients were followed up to 9 years, and the abilities of all variables to predict outcome were assessed. Both neopterin (P = 0.0008) and interleukin-6 (P = 0.033) were significantly higher in patients with higher stages of the disease. The correlation between interleukin-6 and neopterin was weak but significant (Spearman's rank correlation coefficient, 0.38; P = 0.019). By univariate survival analysis using the product-limit approach, both neopterin (P = 0.0001) and interleukin-6 (P = 0.025) were identified as significant predictors of survival. Multivariate survival analyses by the proportional hazards technique demonstrated that either stage and neopterin or neopterin and interleukin-6 are useful combinations of predictor variables. Thus, interleukin-6, which is supposed to influence progression of multiple myeloma in an autocrine or paracrine manner, failed to contribute to prediction if stage was included in a model. In contrast, neopterin remained significant in all multivariate models. PMID- 1933886 TI - Activation of the autocrine transforming growth factor alpha pathway in human squamous carcinoma cells. AB - Transforming growth factor alpha is an autocrine mitogen for nonneoplastic keratinocytes, which exerts its function by binding to the receptor for epidermal growth factor. In order to determine whether this autocrine pathway is activated in squamous carcinoma cells, we analyzed the production of transforming growth factor alpha as well as the expression and regulation of epidermal growth factor receptors in a panel of human squamous carcinoma cell lines. Immunoreactive transforming growth factor alpha was detectable in squamous carcinoma cells as well as in quiescent nonneoplastic keratinocytes. However, in the absence of exogenous mitogens, only the squamous carcinoma cells secreted the growth factor into the medium, whereas untransformed keratinocytes did not. Each of the squamous carcinoma cell lines expressed significantly greater numbers of cell surface epidermal growth factor receptors than normal keratinocytes. The epidermal growth factor receptor gene was amplified and overexpressed in three of the squamous carcinoma cell lines (A431, CaSki, SqCC/Y1). Two of the squamous carcinoma cell lines (C4-1 and CE-48) displayed a relative inability to down regulate epidermal growth factor receptors in response to epidermal growth factor. The mechanism of receptor overexpression in the remaining three cell lines (A253, CaLu-1, FaDu) is unexplained. Thus, human squamous carcinoma cell lines frequently exhibit a combination of the constitutive secretion of transforming growth factor alpha and the overexpression of epidermal growth factor receptors. Treatment of these tumor cells with an antibody directed against the ligand-binding domain of the epidermal growth factor receptor inhibited their growth by approximately 50%. These findings suggest that designing strategies to interrupt the transforming growth factor alpha autocrine pathway might lead to new modalities to treat this class of malignant tumors. PMID- 1933887 TI - A phase I clinical and pharmacokinetic trial of hepsulfam. AB - Hepsulfam (1,7-heptanediol-bis-sulfamate) is one of a series of bis-sulfamate acid esters that was synthesized in an attempt to improve the antitumor efficacy of busulfan. Hepsulfam has shown broad antineoplastic activity in preclinical studies. This Phase I trial evaluated hepsulfam given as a single i.v. dose every 21-35 days. Twenty-nine patients with refractory solid tumors participated in this study. Twenty-six of these patients had had either prior chemotherapy or radiation therapy. Fifty-two courses of treatment were given at doses ranging from 30 to 360 mg/m2/day. The dose limiting toxicity was prolonged thrombocytopenia and granulocytopenia. This toxicity was cumulative with Grade 3 or 4 thrombocytopenia occurring in 3 of 15, 4 of 9, and 2 of 2 patients in the first, second, and third courses of greater than or equal to 210 mg/m2, respectively. This toxicity was noted in patients with less than or equal to 1 prior chemotherapeutic regimen, as well as in patients with greater than 1 prior chemotherapeutic regimens. Nonhematological toxicities included Grade 1 or 2 nausea and vomiting and fatigue. There was no evidence of pulmonary toxicity. Plasma levels of hepsulfam were quantified by gas chromatography in 12 patients. The plasma and blood half-lives were 15.9 +/- 4.6 and 90 +/- 13 h, respectively. No objective tumor responses were seen. We conclude that the maximally tolerated dose when hepsulfam is given as a single dose every 35 days is 210 mg/m2, but that there is significant risk of cumulative hematological toxicity at this level. PMID- 1933888 TI - Differential induction of secondary DNA fragmentation by topoisomerase II inhibitors in human tumor cell lines with amplified c-myc expression. AB - In order to understand the cellular events associated with cell death after the formation of topoisomerase II-DNA cleavable complexes, we compared the induction of endonucleolytic DNA fragmentation by etoposide and its more potent analog, teniposide (VM-26) in the human cell lines HT-29 and HL-60. A new filter-binding assay is described, which allows rapid quantification of nonprotein-linked DNA fragmentation involved in apoptosis. Both cell lines showed similar loss of colony formation ability following 30 min of treatment with various VM-26 concentrations even though the initial topoisomerase II-mediated DNA single strand break frequency was higher in HL-60 cells. DNA repair studies following drug removal indicated that VM-26-induced DNA breaks reversed rapidly and completely in HT-29 cells, while in HL-60 cells, the initial lesions persisted at and above 5 microM VM-26. In both cell lines, topoisomerase II cleavage complexes, as measured by DNA-protein cross-links by alkaline elution, reversed rapidly and completely within 2-3 h. Secondary DNA fragmentation resembling chromatin endonucleolytic cleavage by apoptosis could be detected in HL-60 cells 3 h after VM-26 or etoposide treatment but not in HT-29 cells. Secondary DNA fragmentation was also induced in the human colon cancer cell lines COLO 320, which have c-myc amplification. Since HL-60 cells also have c-myc amplification and HT-29 do not, it is possible that c-myc overexpression may be involved in secondary DNA fragmentation. Finally, our results indicate heterogeneity of cell death mechanisms after exposure to topoisomerase II inhibitors among human cancer cell lines. PMID- 1933889 TI - Effect of antitumor diarylsulfonylureas on in vivo and in vitro mitochondrial structure and functions. AB - Diarylsulfonylureas are novel oncolytic agents shown to have therapeutic activity against both rodent solid tumors and xenografts of human tumors in mice. Previous studies have shown that diarylsulfonylureas localize in mitochondria and cause morphological changes in these organelles. We have investigated the mechanism of action of diarylsulfonylureas, namely, N-(5-indanylsulfonyl)-N'-(4 chlorophenyl)urea (ISCU) and the N-4-methyl analogue (MPCU), by studying their effect on mitochondrial morphology and uptake of rhodamine 123 in GC3/c1 cells in culture and the oxidative phosphorylation in isolated mitochondria from mouse liver, using pyruvate-malate and succinate as substrates. Morphometric analysis of mitochondria in GC3/c1 cells exposed to ISCU showed that ISCU (165 microM) doubled the mitochondrial size after 24-h exposure in culture. Also, ISCU (100 microM), like 40 microM carbonylcyanide p-trifluoromethoxyphenylhydrazone, significantly reduced the rhodamine 123 uptake by GC3/c1 cells studied by flow cytometry. In isolated mitochondria both ISCU and MPCU uncoupled oxidative phosphorylation at 50 microM, with pyruvate-malate as substrate, as was indicated by a significant increase in the State 4 oxygen consumption. This resulted in the loss of ADP phosphorylation and, therefore, the ADP/oxygen ratio was reduced to zero and the respiratory control ratio to one. The succinate oxidation was also significantly impaired by ISCU, causing some decrease in ADP phosphorylation. On the other hand, MPCU did not exhibit any significant effect on the oxidation of succinate. At concentrations of lower than 50 microM, both of these compounds exhibited a deleterious effect, causing damage to mitochondrial functions in the presence of pyruvate-malate as substrates. These data confirm, through morphometric analysis, our previous qualitative observations of abnormal mitochondrial morphology observed in GC3/c1 cells grown in the presence of high concentrations of ISCU and MPCU and further suggest that diarylsulfonylureas, by uncoupling mitochondrial oxidative phosphorylation, may lower cellular ATP. It is probable that this mechanism contributes, at least partially, to cytotoxicity in GC3/c1 cells exposed to high concentrations of ISCU for relatively brief periods (2 to 4 h) and possibly contributes to cytotoxicity at drug concentrations that can be achieved in rodents. PMID- 1933890 TI - Quantitative analysis of genetic susceptibility to liver and lung carcinogenesis in mice. AB - One-week-old male and female mice of the A, BALB/c (C), and C3H/He (C3) strains and of the AC3 and CC3 F1 hybrids were treated with a single dose (300 mg/kg s.c.) of urethan and then kept without further treatment until 30 and 40 weeks (males) or 30 and 65 weeks (females). The degree of difference in susceptibility to hepatocarcinogenesis between the susceptible C3 and the resistant A and C mice, in the different age and sex groups, was 4-12-fold by the analysis of the number of nodules/cm3 (N/cm3), which represents an estimation of tumor frequency and was more than 400-fold as indicated by the percentage of liver volume occupied by nodules (V%), an estimation of tumor size. With regard to lung carcinogenesis, mice of the A strain proved 5-10- and 20-70-fold more susceptible than the C and the C3 mice, respectively, as indicated by the number of microscopically identified lung tumors/mouse (N), an estimation of tumor frequency. The lung tumor size, as estimated by the mean tumor volume (V), was similar in A and C mice but much higher in the A than in the C3 groups (13- approximately 1000-fold difference). The AC3 hybrid was highly susceptible to both liver and lung carcinogenesis. The CC3 hybrid was as susceptible to lung carcinogenesis as its C parent and had an intermediate susceptibility to hepatocarcinogenesis. Our results indicate that a major determinant in the genetic susceptibility to hepatocarcinogenesis, and perhaps to lung carcinogenesis too, is tumor growth, as evidenced by a much greater tumor size in genetically susceptible than resistant mice. PMID- 1933891 TI - Participation of p53 protein in the cellular response to DNA damage. AB - The inhibition of replicative DNA synthesis that follows DNA damage may be critical for avoiding genetic lesions that could contribute to cellular transformation. Exposure of ML-1 myeloblastic leukemia cells to nonlethal doses of the DNA damaging agents, gamma-irradiation or actinomycin D, causes a transient inhibition of replicative DNA synthesis via both G1 and G2 arrests. Levels of p53 protein in ML-1 cells and in proliferating normal bone marrow myeloid progenitor cells increase and decrease in temporal association with the G1 arrest. In contrast, the S-phase arrest of ML-1 cells caused by exposure to the anti-metabolite, cytosine arabinoside, which does not directly damage DNA, is not associated with a significant change in p53 protein levels. Caffeine treatment blocks both the G1 arrest and the induction of p53 protein after gamma irradiation, thus suggesting that blocking the induction of p53 protein may contribute to the previously observed effects of caffeine on cell cycle changes after DNA damage. Unlike ML-1 cells and normal bone marrow myeloid progenitor cells, hematopoietic cells that either lack p53 gene expression or overexpress a mutant form of the p53 gene do not exhibit a G1 arrest after gamma-irradiation; however, the G2 arrest is unaffected by the status of the p53 gene. These results suggest a role for the wild-type p53 protein in the inhibition of DNA synthesis that follows DNA damage and thus suggest a new mechanism for how the loss of wild type p53 might contribute to tumorigenesis. PMID- 1933892 TI - Biological monitoring of low-dose interleukin 2 in humans: soluble interleukin 2 receptors, cytokines, and cell surface phenotypes. AB - Different immunotherapy regimens using s.c. recombinant interleukin-2 (rIL-2) were studied in 76 patients with progressive metastatic renal carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, or Hodgkin's disease. To assess the immunomodulatory capacity of rIL-2, we measured serum levels of soluble interleukin-2 (sIL-2) receptors, gamma-interferon, tumor necrosis factor alpha, and various lymphocyte subsets expressing the CD25 Tac IL-2 receptor and the CD56 natural killer (NK) associated antigen. Additionally, we measured serum antibodies specific to rIL-2 in order to evaluate immunogenicity of rIL-2. In all patients, a significant increase in sIL-2 receptor levels could be observed when comparing values on day 0 and after one treatment course. Patients developing a neutralizing anti-rIL-2 antibody exhibited significantly lower serum sIL-2 receptor levels than patients without antibody. Soluble IL-2 receptors correlated with the percentage of CD25 IL-2 receptor-positive peripheral blood lymphocytes. Both soluble and cell surface IL-2 receptors exhibited a significant increase during rIL-2 therapy but did not correlate with the percentage of CD56-positive peripheral blood lymphocytes. Measurement of treatment-induced secondary cytokines showed significant increases in gamma-interferon serum levels in a proportion of patients tested, although with considerable interindividual variability. No significant increase in mean tumor necrosis factor-alpha levels was observed during rIL-2 treatment in vivo. The percentage of CD56-positive NK cells correlated with the clinical outcome of rIL-2 therapy. Thus, partial or complete responders had an increase from a mean of 20% NK cells prior to therapy up to a mean of 40% after the first treatment course. In contrast, patients with progressive disease had a mean of 22 and 24% NK cells before and after treatment, respectively. PMID- 1933893 TI - Phase I pharmacokinetic and pharmacodynamic study of a new anthrapyrazole, CI-937 (DUP937). AB - We performed a phase I trial of CI-937 (DUP937), an anthrapyrazole, with the following objectives: (a) to determine the maximally tolerated dose in humans; (b) to define the toxicity spectrum of this agent; (c) to describe the pharmacokinetics of the drug; (d) to test a pharmacokinetics based hypothesis of dose escalation; and (e) to relate drug pharmacokinetics to pharmacodynamics. CI 937 was administered as a single bolus injection every 3-4 weeks at doses ranging from 3.6 to 25.2 mg/m2. Thirty-two patients and 57 courses were evaluable for toxicity. Pharmacokinetic analysis was performed in 30 patients on the first course using a sensitive and selective radioimmunoassay. The maximally tolerated dose in patients with no prior therapy was 25.2 mg/m2 and dose-limiting toxicity was neutropenia. Thrombocytopenia, nausea, vomiting, stomatitis, and alopecia were mild. A partial response was recorded in a patient with mesothelioma. The area under the curve increased linearly with dose, and total body clearance of CI 937 was independent of dose. The mean total body clearance was 107 +/- 55.8 ml/min/m2, mean steady state volume of distribution was 492 +/- 469 liters/m2, and terminal half-life was 3.78 +/- 2.86 days. The extended factors of 2 methods of pharmacologically guided dose escalation were intended for use but ultimately were equivalent to that of the modified Fibonacci dose escalation method. Dose and the area under the curve were significant predictors of a percentage change in WBC and neutrophil count in a univariate analysis. Only dose and baseline neutrophil count predicted a percentage change in WBCs in a multifactor analysis. Dose and prior chemotherapy predicted percentage change in neutrophil count in a multifactor analysis. We conclude that the dose-limiting toxicity of CI-937 is neutropenia and that the recommended phase II starting dose is 22 mg/m2. PMID- 1933894 TI - Experimental and clinical observations on hepatic cryosurgery for colorectal metastases. AB - Cryosurgery, using liquid nitrogen at -196 degrees C, was explored for treating colorectal liver metastases in an experimental study of rat colon cancer and in a clinical investigation of patients with unresectable liver tumors. The viability of rat colon cancer isografts showed that while two or three freeze-thaw cycles were 100% effective in controlling established isografts and preventing isograft take, one freeze-thaw cycle was suboptimal. In these animals cryosurgery was as effective as surgical resection in controlling established experimental liver metastases. Cryosurgery by operative liver exposure and intraoperative ultrasound monitoring were used to treat liver metastases from colorectal cancer in 24 patients. At a median follow-up of 2 years (range, 5 months to 5 years), seven patients (29%) are disease free, eight (33.5%) are alive with recurrent tumors, and nine (37.5%) have died. The patterns of failure were: remaining liver and extrahepatic sites, ten patients (59%); remaining liver only, six patients (35%); and extrahepatic only, one patient (6%). These data demonstrate that cryosurgery is a useful modality for treating unresectable primary and metastatic liver cancers. Addition of systemic adjuvant therapy may improve the tertiary failure following the control of liver metastases. PMID- 1933895 TI - E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. AB - Tissue sections of 32 squamous cell carcinomas (SCCs) of the head and neck were investigated for the expression of the epithelium-specific cell adhesion molecule E-cadherin. We found that E-cadherin expression is inversely correlated both with the loss of differentiation of the tumor and with lymph node metastasis. The well differentiated SCCs expressed E-cadherin, often as strongly as the normal stratified epithelium (12 cases were tested); the moderately differentiated SCCs expressed intermediate amounts of E-cadherin or were heterogeneous (15 cases were analyzed); whereas the poorly differentiated SCCs were all E-cadherin-negative (five cases were investigated). Furthermore, seven of eight infiltrated lymph nodes of SCCs were E-cadherin-negative. These data indicate that the loss of the cell adhesion molecule E-cadherin in fact plays an important role in the progression of human squamous cell carcinomas, i.e., that down-regulation of expression is associated with dedifferentiation and metastasis of the tumor cells in vivo. PMID- 1933897 TI - Immunocytochemical localization of parathyroid hormone-like peptide in the rat fetus. AB - Studies of parathyroid hormone-like peptide (PLP) have demonstrated that PLP gene expression is inducible by serum, growth factors, and cycloheximide. Rapid induction of PLP gene expression has also been observed following the induction of cell differentiation. These features of PLP gene expression are consistent with a role for PLP in the regulation of cell growth and differentiation. To understand the biology of PLP in developing cells and tissues, we have studied the distribution of PLP gene expression in the fetal and neonatal rat. PLP was localized by immunocytochemistry to skin, vascular smooth muscle, skeletal muscle, heart, liver, kidney, lung, and gastrointestinal tract in Day 14 fetal rat. By Day 18 PLP immunopositivity was also detected in both fetal pituitary and adrenal medulla, as well as in endocrine pancreas. Whereas few PLP-immunopositive cells were detected in Day 14 brain, scattered areas of PLP immunopositivity were evident in Day 18 brain, in regions such as the choroid plexus. Immunostaining for PLP was also detected in Day 18 tissues that were positive on Day 14. The pattern of staining in fetal testis, where PLP was strongly localized to seminiferous tubules, differed from adult testis, where PLP was localized predominantly in Leydig cells. PLP was localized to the hepatocytes but not to the hematopoietic elements in fetal liver. Neonatal hepatocytes were weakly PLP immunopositive, and PLP was not detected in adult rat liver. Northern blot analysis demonstrated the presence of a single 1.4-kilobase PLP mRNA transcript in fetal brain, liver, heart, lung, and intestine. The results of these studies demonstrate that the PLP gene is widely expressed in a diverse number of fetal rat tissues. The cellular and tissue localization of PLP immunopositivity remains fairly constant in the transition from fetal to neonatal and adult tissues except in the testis, where a cellular switch in PLP-producing cells occurs, and the liver, where PLP gene expression is progressively extinguished postnatally. PMID- 1933896 TI - Differential expression of N-myc in phenotypically distinct subclones of a human neuroblastoma cell line. AB - Neuroblastomas are malignant childhood neoplasms that arise from derivatives of the neural crest. We report the characterization of a new neuroblastoma cell line, designated NBL-W, derived from the primary tumor of a patient with stage IVS disease (S. L. Cohn, C. V. Herst, H. S. Maurer, and S. T. Rosen, J. Clin. Oncol., 5: 1441-1444, 1987) according to the criteria of Evans [A. E. Evans, G. J. D'Angio, and J. Randolf, Cancer (Phila.), 27: 374-378, 1971]. Neurite-bearing (N) and substrate-adherent (S) cell lines have been subcloned from the parent line. N and S cells can interconvert, and both cell types label with the neural crest cell surface marker antibody, HNK-1. Cells in the subcloned lines and in the parent line have been shown by Southern blot analysis to contain approximately 100 copies of the N-myc gene. Cytogenetic analysis shows a homogeneously staining region present on chromosome 19. Although these subclones are of identical genotype, the S cells express lower amounts of N-myc mRNA and protein as compared to the N cells. N cells express several neuronal proteins including the neurotransmitter-processing enzymes tyrosine hydroxylase and dopamine beta-hydroxylase, the neuronal intermediate filament proteins peripherin and NF66/alpha-internexin, and the neural cell adhesion molecule. S cells generally lack neuronal markers but express the mesenchymal intermediate filament protein vimentin, and a small subset of the S cells express glial fibrillary acidic protein. Some S cells were labeled weakly with neural cell adhesion molecule antibody; others were negative. S cells did not express the glial marker S-100 or a melanocyte marker, tyrosinase. Thus, S cells express the neural crest marker HNK-1 but do not express a set of antigens characteristic of any known cell type derived from the neural crest. These results are consistent with the suggestion that differential N-myc expression may be involved in the interconversion of N and S cells but indicate that the S cell phenotype need not represent a highly differentiated neural crest derivative. PMID- 1933898 TI - Malignant behavior and resistance to cisplatin of human ovarian carcinoma xenografts established from the same patient at different stages of the disease. AB - Three human ovarian carcinoma lines (HOC8) derived from the same patient before (P-HOC8) and after (R-HOC8 and Y-HOC8) cycles of chemotherapy were established i.p. in nude mice. The biological characterization showed that these tumor lines had various features in common. Cytological and histopathological characteristics and the expression of tumor-associated antigens OC125 and MOV18 were maintained in the three variants and were comparable to the patient's primary tumor. The HOC8 variants were aneuploid with a chromosome mode number of 80-81. All three tumor lines grew better i.p. than s.c. in nude mice. After i.p. injection the HOC8 lines produced ascites in all the mice, infiltration of pancreas, liver, diaphragm, and lung metastases. The sensitivity to cisplatin was evaluated for HOC8 lines growing in nude mice and mirrored the clinical development of resistance. Treatment with cisplatin of mice transplanted i.p. with P-HOC8 (obtained before the patient received chemotherapy) resulted in a significant increase in survival time; the R-HOC8 and Y-HOC8 lines (obtained after chemotherapy) were less sensitive. HOC8 xenografts, which represent the course of a single patient's disease, are a useful model for investigating the development of drug resistance in ovarian carcinoma. PMID- 1933899 TI - Construction, binding properties, metabolism, and tumor targeting of a single chain Fv derived from the pancarcinoma monoclonal antibody CC49. AB - CC49 is a "second generation" monoclonal antibody to B72.3, which reacts with the pancarcinoma antigen TAG-72. CC49 has been shown to efficiently target human colon carcinoma xenografts and is currently being evaluated in both diagnostic and therapeutic clinical trials. We describe here the construction and characterization of a recombinant single-chain Fv (sFv) of CC49. The sFv was shown to be a Mr 27,000 homogeneous entity which could be efficiently radiolabeled with 125I or 131I. Comparative direct binding studies and competition radioimmunoassays using CC49 intact IgG, F(ab')2, Fab', and sFv revealed that the monomeric CC49 Fab' and sFv had relative binding affinities 8 fold lower than the dimeric F(ab')2 and intact IgG. Nonetheless, the 131I-labeled sFv was shown to bind biopsies of TAG-72-expressing tumors. Metabolism studies in mice, using radiolabeled CC49 IgG, F(ab')2, Fab', and sFv, demonstrated an extremely rapid plasma and whole body clearance for the sFv. CC49 sFv plasma pharmacokinetic studies in rhesus monkeys also showed a very rapid plasma clearance (T1/2 alpha of 3.9 min and T1/2 beta of 4.2 h). Tumor targeting studies with all four radiolabeled Ig CC49 forms, using the LS-174T human colon carcinoma xenograft model, revealed a much lower percentage injected dose/g tumor binding for the CC49 monomeric sFv and Fab' as compared to the dimeric F(ab')2 and intact IgG. However, tumor:normal tissue ratios (radiolocalization indices) for the sFv were comparable to or greater than those of the other Ig forms. High kidney uptake with 125I-labeled Fab' and F(ab')2 was not seen with 125I-sFv. Gamma scanning studies also showed that 131I-CC49 sFv could efficiently localize tumors. The CC49 sFv may thus have utility in diagnostic and perhaps therapeutic applications for a range of human carcinomas. PMID- 1933900 TI - Expression of HLA-A,B,C antigens on primary and metastatic tumor cell populations of human carcinomas. AB - The expression of monomorphic determinants of the histocompatibility leukocyte antigens (HLA) class I antigens by human malignant tumor cells was studied in tissue specimens of 70 primary tumor lesions obtained from patients with carcinoma of the breast (41 patients), colon (8 patients), urinary bladder (8 patients), and kidney (13 patients), and in samples of either synchronous or metachronous lymph node, lung, or liver metastases available in 44 of the patients. The frequencies of HLA class I expressor and nonexpressor tumor cells were determined by immunohistochemical staining of histological sections of fresh frozen tissue samples with the W6/32 monoclonal antibody. The tumor cell populations in the majority of the primary lesions consisted predominantly of HLA immunoreactive cells (observed in 38 of 70 patients; 54%), especially in those patients who did not have clinical evidence of metastatic disease (8 of 11 patients; 73%). Various degrees of loss of reactivity were observed in other primary lesions, although in only 8 (12%) tumors (7 of which were obtained from patients with metastatic disease), the neoplastic cells were nearly exclusively HLA-nonreactive. In contrast, the majority of metastatic lesions consisted of either predominantly HLA-negative cells (33 of 44 specimens; 75%) or mixed populations (10 of 44 specimens; 23%), whereas only one metastatic lesion manifested HLA class I antigen staining in more than 70% of its tumor cells (P = 0.0005). Intravascular clusters of tumor cells consisted predominantly of HLA class I nonexpressors. The observed patterns of distribution of HLA expressors and nonexpressor tumor cells are compatible with the notion that HLA-negative cells in human carcinomas manifest a selective advantage with regard to metastatic progression and growth. The suppressed expression of major histocompatibility complex class I antigens on metastatic cells may lead to failure of presentation of cell surface tumor specific epitopes to host cytotoxic T-lymphocytes. Such a process would enable tumor cells to evade host immune responses and would promote and enhance cell dissemination and metastatic growth. PMID- 1933901 TI - Intraocular tumor suppression of retinoblastoma gene-reconstituted retinoblastoma cells. AB - Human retinoblastoma is caused by mutational inactivation of the retinoblastoma suppressor gene (RB). We have examined intraocular tumorigenicity of retinoblastoma cells in which RB expression was achieved by retroviral transduction. Retinoblastoma cells were injected into the anterior chambers of severe combined immunodeficient mouse eyes, and tumorigenicity was assessed. RB expressing retinoblastoma cells usually failed to form progressive tumors in the anterior chamber, whereas the parental, RB-negative line, WERI-Rb27, was rapidly tumorigenic. These results support the hypothesis that inactivation of the RB gene is critical for the growth of retinoblastoma tumors. The potential use of RB reconstitution for treating human retinoblastoma is suggested by our finding that intraocular tumor growth can be suppressed by RB expression. PMID- 1933902 TI - A germ line mutation in exon 5 of the p53 gene in an extended cancer family. AB - Germ line p53 point mutations have been reported for some families with Li Fraumeni syndrome, a syndrome characterized by a dominantly inherited increased susceptibility for the development of early age of onset neoplasms of diverse origin in multiple family members. All of the initially reported p53 germ line mutations have been found exclusively within a single conserved, nonpolymorphic region of the gene between condons 245 and 258. The restricted distribution of these inherited mutations has led to speculation that germ line p53 mutations have unique properties [B. Vogelstein, Nature (Lond.), 348: 681-682, 1990]. We report here on the identification of a p53 germ line mutation at codon 133 (ATG-- -ACG) in nine members of an extended Li-Fraumeni syndrome family. This mutation leads to an amino acid substitution in the protein and is shown to completely cosegregate with Li-Fraumeni syndrome associated cancer in this family. Its location extends the region of the p53 gene where inherited mutations predisposing to cancer are observed and suggests that their distribution may be diverse. PMID- 1933903 TI - Demonstration of the need for end point validation of putative biomarkers: failure of aberrant crypt foci to predict colon cancer incidence. AB - Seven-week-old Sprague-Dawley rats were fed a semipurified AIN76 diet and were given a weekly injection of the colon carcinogen 1,2-dimethylhydrazine for 8 weeks (initiation stage of carcinogenesis). The rats were divided into seven groups and each group of rats was placed on one of seven different modifications of the AIN76 diet for the next 24 weeks (promotional stage of carcinogenesis). The mean numbers of aberrant crypt foci/rat and the incidence of adenocarcinomas from some of the seven dietary groups were found to be significantly different. However, all attempts to show a significant correlation between the mean number of aberrant crypt foci/rat and the incidence of adenocarcinomas failed. Therefore, the number of aberrant crypt foci/rat cannot by itself be used as a reliable quantitative predictor (biomarker) of the efficacy of dietary intervention or of chemopreventive procedures on modulating the risk of developing colon cancer. This conclusion emphasizes the need for end point validation of potential cancer biomarkers before the biomarkers can be considered predictive of modulation of the risk for colon cancer. PMID- 1933904 TI - p53 gene mutations and abnormal retinoblastoma protein in radiation-induced human sarcomas. AB - The potentially carcinogenic effect of therapeutic irradiation has been recognized for many years. Second malignancies, usually sarcomas, are known to arise within or at the edge of radiation fields after a period of several years after the initial radiation exposure. We analyzed tumor cells derived from seven radiation-induced tumors for abnormalities in tumor suppressor genes p53 and retinoblastoma at the DNA sequence and/or protein level. p53 mutations were detected by exon-specific polymerase chain reaction amplification and single strand conformation polymorphism analysis of exons 5-8 followed by direct genomic sequencing of those tumors exhibiting a variant pattern. The p53 gene was abnormal in three of six sarcomas studied. Retinoblastoma gene analysis was performed by Western immunoblot; retinoblastoma protein was under-phosphorylated in three of seven tumors and absent in one other. In all, six of seven radiation induced human tumors have abnormalities of one or both suppressor genes. Inactivation of tumor suppressor genes by ionizing radiation may contribute to radiation carcinogenesis. PMID- 1933905 TI - Mechanistic and statistical insight into the large carcinogenesis bioassays on N nitrosodiethylamine and N-nitrosodimethylamine. PMID- 1933906 TI - Effects on 4080 rats of chronic ingestion of N-nitrosodiethylamine or N nitrosodimethylamine: a detailed dose-response study. AB - Four thousand eighty inbred rats were maintained from weaning on various different concentrations of N-nitrosodiethylamine (NDEA) or N nitrosodimethylamine (NDMA). The principal aim was to characterize the dose response relationship for the effects of these agents on esophageal cancer (NDEA) or on various types of liver cancer (NDEA and NDMA), although NDEA also caused a few tumors of the nasopharynx and NDMA also caused a few tumors of the lung. The numbers of tumors of mesenchymal and Kupffer cells in the liver were too few to allow easy characterization of the dose-response relationships, and although NDMA induced large numbers of bile duct neoplasms, NDEA did not. Thus, the four principal dose-response relationships studied were of NDEA on esophageal or liver cells and of NDMA on bile duct or liver cells. At doses sufficiently high for the median time to death from the disease of interest to be estimated, relationships were observed of the general form (Dose rate) x (median)n = constant where n was about 2.3 for the first three relationships and about 1 for the last one (NDMA on liver cell tumors). By contrast, at doses sufficiently low for longevity to be nearly normal (median survival about 2.5 years), there remained no material dependence on the dose rate of the age distribution of the induced neoplasms. At these low dose rates, the number of liver (but not of esophageal) neoplasms induced by treatment was simply proportional to the dose rate. This finding is not surprising, since the background incidence of liver (but not of esophageal) neoplasms was appreciable. The linear relationship observed at low dose rates (below 1 ppm) suggests that under these experimental conditions, among rats allowed to liver their natural life span, a dose of 1 ppm of NDEA or NDMA in the drinking water will cause about 25% to develop a liver neoplasm, a dose of 0.1 ppm will cause about 2.5% to do so, and a dose of 0.01 ppm will cause about 0.25% to do so, etc., with no indication of any "threshold." (At these low dose rates, the incidence of liver neoplasms appears likely to exceed greatly that of esophageal neoplasms.) In addition, even quite low dose rates of the test agents caused a variety of nonneoplastic liver abnormalities (e.g., hyperplastic nodules, or shrinkage of hepatocytes) at a frequency roughly proportional to the dose rate. PMID- 1933907 TI - Dose and time relationships for tumor induction in the liver and esophagus of 4080 inbred rats by chronic ingestion of N-nitrosodiethylamine or N nitrosodimethylamine. AB - A Weibull analysis is presented of the dose and time relationships for the effects on 4080 inbred rats of chronic ingestion in the drinking water of 16 different doses of N-nitrosodimethylamine (NDMA) or N-nitrosodiethylamine (NDEA). The sites chiefly affected were the liver (by both agents) and the esophagus (by NDEA only). Since the experiment continued on into extreme old age, effects became measurable at doses of only 0.01 to 0.02 mg/kg/day, which is an order of magnitude lower than previously achieved. (After only 2 years of treatment, however, the TD50 doses needed to halve the proportion of tumorless survivors would have been about 0.06 mg/kg/day of NDEA, or about 0.12 mg/kg/day of NDMA.) The general pattern of response was that the natural logarithm of the probability of remaining tumorless was given by the product of two terms, the first (the "Weibull b value") depending on the dose rate but not on the duration of exposure and the second depending not on dose at all but only on duration. For all types of tumor the dependence on duration was fairly similar (and for each the second term was taken to be -t7, where t = years of treatment), but for different types of tumor the dependence on dose rate was quite different. For esophageal tumors, the "Weibull b value" was approximately proportional to the cube of the dose rate of NDEA (males 21 d3, females 11 d3, where d = dose rate in mg/kg adult body weight/day), and the background incidence was unmeasurably low. For liver tumors induced by NDEA, the b value was approximately proportional to the fourth power of dose rate + 0.04 mg/kg/day [males, 19 (d + 0.04)4; females, 32 (d + 0.04)4], although the relationships were somewhat different for the different cell types of liver tumor. This one formula implies both approximate linearity at low doses and an approximately cubic relationship within the higher range of doses that was studied. For liver tumors induced by NDMA, the Weibull b value was approximately proportional to the sixth power of dose rate + 0.1 mg/kg/day [males, 37 (d + 0.1)6; females, 51 (d + 0.1)6], again with some variation between liver cell types, and again implying approximate linearity at low doses. These algebraic formulae should, of course, be trusted only in the range of doses where they were derived, and particularly not above it.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1933908 TI - Chronic nitrosamine ingestion in 1040 rodents: the effect of the choice of nitrosamine, the species studied, and the age of starting exposure. AB - In parallel with a larger experiment on 4080 rats fed 16 different concentrations of N-nitrosodiethylamine (NDEA) or N-nitrosodimethylamine (NDMA) from 6 weeks of age, a variety of smaller experiments on a total of 1040 rodents were undertaken and are the subject of the present report. Three separate subjects were addressed. Studies of 16 different concentrations of N-nitrosopyrrolidine and N nitrosopiperidine given from age 6 weeks onwards to small groups of rats yielded dose-response relationships for the effects of N-nitrosopyrrolidine on liver tumors and for those of N-nitrosopiperidine on tumors of the liver and upper gastrointestinal tract that resembled those seen for NDMA and NDEA, respectively, except that N-nitrosopyrrolidine and N-nitrosopiperidine were less potent [the respective dose rates needed to halve the proportion of tumorless survivors after 2 years of treatment being approximately 0.4 (males) and 0.6 (females) mg/kg adult body weight/day for each agent]. Alternatively, it was estimated that the risks to rats from lifelong exposure to 1 microgram/kg adult body weight/day of each agent might be about 0.1%, and that the risks to rats from lower doses would be proportionately less. Studies of 16 different concentrations of NDEA on small groups of female mice and female hamsters yielded the types of dose response that would be expected for upper gastrointestinal tumors, liver cell tumors, and Kupffer cell tumors in mice (no other types of liver tumor being produced, in contrast with previous reports) and for tracheal and liver cell tumors in hamsters (no clear effect on upper gastrointestinal tumors being apparent in hamsters). The dose rates needed to halve the proportion of tumorless survivors after 2 years of treatment were approximately 0.3 mg/kg adult body weight/day, i.e., 5 times that for the same agent in rats. In part, however, this may be because treatment started at an older age in these species. Studies were undertaken of the effects on esophageal and liver tumorigenesis of starting the treatment of rats with NDEA at 3 or at 20 weeks of age instead of at 6 weeks of age (as in the main experiment). Earlier treatment resulted in slightly greater dosage rates, if dosage was measured in mg/kg/day, and hence in a correspondingly more rapid yield of esophageal tumors, but the effect was not large. By contrast, an earlier start to treatment resulted, after a fixed duration of treatment, in animals having a 3-fold higher incidence rate of liver tumors, while a later start resulted in a 2-fold decrease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1933909 TI - Cardioxane--ICRF-187 towards anticancer drug specificity through selective toxicity reduction. PMID- 1933910 TI - Prognostic factors in Hodgkin's disease. PMID- 1933911 TI - Epidural spinal cord compression from metastatic tumor: diagnosis and guidelines for management. PMID- 1933912 TI - Carbetimer: a re-evaluation of a drug with a novel mechanism of action. PMID- 1933913 TI - Histologic prognostic factors in ependymoma. AB - The prognostic value of a series of histologic signs and clinical features was studied in a series of 298 ependymomas, collected from different institutions. The distribution of tumor sites varied in relation to patient age, with infratentorial cases prevailing under 4 years. Life table univariate analysis demonstrated as highly significant prognostic factors: (1) the number of mitoses; (2) endothelial hyperplasia; (3) necrosis; (4) intracranial site; (5) age less than 4 years. Multivariate analysis by tumor site revealed mitoses cell density, age greater than 16 years in supratentorial cases, and subependymoma in infratentorial cases to be prognostically important. Comparison of the anaplastic variant with the other tumor types in intracranial cases did not show a significant difference in survival even though the median survival time of anaplastic cases was shorter. The main conclusion is that the histological criteria employed to diagnose anaplasia in ependymomas. The number of mitoses is a very important prognostic factor in supratentorial cases, whereas endothelial proliferations and necroses are much less important as prognostic factors than in gliomas. PMID- 1933915 TI - Ventriculojugular shunt against the direction of blood flow. IV. Technical modifications and policy for treatment. AB - During evolution of the surgical procedure to implant ventriculojugular (VJ) shunts against the direction of blood flow for the treatment of hydrocephalus, various modifications were made in the shunting catheter and in the implantation technique with the aim of improving the results. Shunt implantation was difficult in infants and young children with compressible craniums and the modifications failed to improve the results. Accordingly, they were not considered suitable for this method of cerebrospinal fluid (CSF) shunting. Our present policy is to implant VJ shunts in hydrocephalic patients with rigid craniums and ventriculoperitoneal (VP) shunts in infants and young children to tide them over a period until they become suitable for VJ shunting. During the past 5 years, 110 hydrocephalic patients with rigid craniums were treated by implanting VJ shunts without need for further modifications. The shunt was revised in one patient during the early postoperative period due to CSF leakage under the scalp. There were no complications related to CSF overdrainage in any of the cases. PMID- 1933914 TI - Head injuries in infants and young children: the value of the Paediatric Coma Scale. Review of literature and report on a study. AB - The normal verbal and motor responses embodied in the standard Glasgow Coma Scale (GCS) are not achievable during the first few years of life. The recent literature contains numerous reports of attempts to devise scales of responses quantitating the conscious level in infants and young children, both for research purposes and as clinical guides; some of these scales incorporate items, e.g. brainstem reflexes, that are not included in the GCS. We have reported on a simple paediatric version of the GCS, which uses the standard scale with minor modifications in the verbal component, and sets realistic age-related normal responses. This has been tested prospectively in a series of 60 head-injured infants and children (age range 0-72 months). Of 6 cases recorded as comatose 6 h after injury, 4 have confirmed or suspected residual disabilities. Of 35 cases considered to be fully conscious at 6 h, 31 have made good recoveries and only 1 has suspected residual disabilities. The study suggests that the scale accords with the realities of neurological immaturity, and confirms that it can be used in routine paediatric practice. For comparative therapeutic trials, the conscious level in infants has limited value as an index of brain injury, and should be complemented by other indices, such as brainstem reflexes. PMID- 1933916 TI - Infantile hydrocephalus: brain sonography as an effective tool for diagnosis and follow-up. AB - Infantile hydrocephalus is a common disease. In most affected children the process starts before the age of 2 when the bregmatic fontanel is still open. Brain sonography has emerged as an effective tool in diagnosing progressive ventricle dilation and may be used for continuous follow-up. It gives such important information as: (a) cortical thickness, an expression of proper shunt function and of prognostic value concerning neuropsychological development; (b) position of the tip of the catheter, which is considered by some to be a predictive factor of shunt failure; (c) other complications such as subdural collections, isolated IV ventricle, and slit ventricles. This methodology permits frequent examinations and allows better comprehension of the pathological process by the parents and medical staff. PMID- 1933917 TI - Distribution of bacteria in the operating room environment and its relation to ventricular shunt infections: a prospective study. AB - In order to study the distribution of bacteria in the operating room environment, cultures were obtained during 111 unselected shunt operations throughout a 10 month period. After routine skin preparation, bacteria were collected by placing Millipore filters on the patient's prepped skin underneath the drapes, on top of the drapes in the operative field, and/or on the sterile instrument table, and left in place for the duration of the case. In 48 patients, full-thickness skin biopsies taken at the initial incision were cultured in lieu of skin surface cultures. Perioperative cerebrospinal fluid cultures and subsequent shunt infections were monitored. Of the 288 environmental (skin and surfaces) cultures, 24 were positive (20 coagulase-negative Staphylococcus and 4 Staphylococcus aureus). Positive cultures were found in 15 of 111 drape cultures (13.5%), 7 of 77 instrument table cultures (9.1%), and 2 of 97 skin cultures (2.1%). Positive environmental cultures were not correlated with the surgeon, length of case, time of day, or type of shunt operation, but were more likely to occur in a room other than the designated neurosurgical operating room. There was a correlation between the occurrence of positive environmental cultures and positive cerebrospinal fluid cultures, although the organisms were not always the same. Coagulase negative Staphylococcus was the most common organism isolated from all sites. We conclude that bacteria most often associated with shunt infections are airborne in the operating room, rather than originating from the patient's skin, and are distributed in the highest concentration near the surgical team.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933918 TI - Fatal cardiopulmonary complications in children treated with ventriculoatrial shunts. AB - During the years from 1965 to 1986, 716 children underwent a total of 2065 shunt procedures in our department. Of these, 1298 were ventriculoatrial (VA). Until 1979, Pudenz VA shunts were almost exclusively used as the primary procedure as well as in revisions. Since 1980, mini-Holter VA shunts have been implanted as a second choice, usually in cases with repeated distal failure in ventriculoperitoneal (VP) shunts. Observation time for children with VA shunts is therefore from 10 to 23 years for the great majority. The cumulative death rate for all patients is 24% (175/716), 9% (64/716) being tumor patients who eventually died as a result of their neoplasm. Most of the other deaths were caused by shunt infection or occurred in a group of children where shunts had been implanted for palliative reasons and where follow-up was only sporadic. Among the 450 children with VA shunts, 15 fatal complications occurred that were directly related to the atrial catheter, resulting in an accumulated incidence of 3% of such serious side effects from VA shunting. Three of these 15 fatal cases presented with nonspecific signs of cardiopulmonary failure following 10-21 years' shunting, and they died from irreversible pulmonary hypertension within a few months. A fourth case of late cor pulmonale has done unexpectedly well and has improved considerably while receiving anticoagulant therapy for over a period of 3 years. PMID- 1933919 TI - Prenatal aqueductal stenosis as a cause of congenital hydrocephalus in the inbred rat LEW/Jms. AB - We studied the microscopic morphological changes in congenital hydrocephalus in the inbred rat, LEW/Jms, on gestational days 17, 18, and 20 and during the neonatal period to clarify the etiopathogenesis, focusing particularly on the aqueductal changes. At 1 day of age, ventriculomegaly was limited to the lateral and III ventricles, and the aqueduct was obstructed, with the appearance of simple stenosis. On gestational days 20 and 18, the hydrocephalic rats showed occluded aqueducts, which paralleled the finding of hydrocephalus in the newborn rats. On gestational day 17, all eight models examined showed the same size ventricles. However, an aqueductal obstruction was observed in one of them. The other seven rats showed the aqueduct patent. From these observations, it can be concluded that the rat shows an aqueductal obstruction on gestational day 17 and appears to develop hydrocephalus with age. The aqueductal obstruction was considered to be the primary change and not a secondary phenomenon. The site of obstruction was the anterior part of the aqueduct (level of anterior colliculus) at every stage. Aqueductal obstruction following the developmental anomaly of the midbrain in the embryonic stage might thus be the primary cause of congenital hydrocephalus in rats LEW/Jms. PMID- 1933921 TI - Apert's syndrome with occipital encephalocele and absence of corpus callosum. AB - A case of Apert's syndrome with posterior (occipital) encephalocele and absence of corpus callosum is described. This is a rare combination. The mechanisms involved are discussed. PMID- 1933920 TI - Spinal extradural hematopoiesis in adolescents with thalassemia. Report of two cases and a review of the literature. AB - Extramedullary hematopoietic tissue occurring within the extramedullary space and causing cord compression is an unusual occurrence in childhood and adolescence, and only four cases have been reported during the first two decades of life. We had the opportunity to treat a 16-year-old girl and a 14-year-old boy with paraparesis secondary to extradural extramedullary hematopoiesis. Findings in these cases are discussed, and an attempt is made to stress once more the possibility of congenital hematopoietic rests as the origin of such hyperplastic tissue. The various modes of therapy are discussed and related literature is reviewed. PMID- 1933922 TI - Intracranial pressure monitoring using a programmable pressure valve and a telemetric intracranial pressure sensor in a case of slit ventricle syndrome after multiple shunt revisions. AB - A case of hydrocephalus showing slit ventricle syndrome after multiple shunt revisions was treated with a programmable pressure valve, and intracranial pressure was monitored with a telemetric sensor. High pressure setting produced positive and normal values of intracranial pressure in this patient. We report our experiences. PMID- 1933923 TI - Fred J. Epstein. PMID- 1933924 TI - Misguided concepts: the bases of scientific advancement. PMID- 1933925 TI - Duplex color ultrasound study of infantile progressive ventriculomegaly. AB - Sequential measurements of ventricular sizes and Doppler variables of anterior cerebral artery (ACA) by duplex color ultrasound were performed on 14 ventriculomegalic infants (mean age: 3.4 months): 9 were postmeningitic, 3 posthemorrhagic, and 2 congenital. According to changes of the frontal horn radius (FHR) after shunts, the FHR was decreased greater than 30% (n = 9) in group I and less than or equal to 10% (n = 5) in group II. Before shunting, Pourcelot index (PI) in group I was greater than in group II (P less than 0.01), but FHR in group II was higher than in group I (P less than 0.01). The intracranial pressure did not vary between groups. Serial preshunt examinations showed a significant correlation between the degree of cerebrovascular resistance and the degree of ventricular dilation only in group I. After surgery, significant changes of end-diastolic velocity, the area under the velocity curve, and PI were found only in group I. The reservoir pumping test performed on 2 cases of recurrent ventriculomegaly in group I and 3 cases in group II showed a decreased PI only in group I, in which the outcome was better. PI is useful in differentiating between hydrocephalic and atrophic ventriculomegaly. These data suggest that a ventriculomegalic infant with an unelevated PI value hardly benefits from a ventricular shunt. PMID- 1933927 TI - Advancement-onlay: an improved technique of fronto-orbital remodeling in craniosynostosis. AB - Eighteen patients with nonsyndromic craniosynostosis underwent fronto-orbital remodeling with an advancement-onlay technique. The mean age of the infants was 5 months (range = 2-11 months) when the procedure was performed for the following indications: unilateral coronal synostosis (n = 10); bilateral coronal synostosis (n = 3); metopic synostosis (n = 2); and multiple craniosynostoses (n = 3). The technique consists of (1) unilateral or bifrontal craniotomy, (2) superior orbital rim recontouring and advancement, and (3) frontal bone graft rotation and onlay. Posteriorly, the frontal bone graft is left "floating," while anteriorly, rigid fixation with microplates and screws has supplanted wire osteosynthesis. The use of rigid fixation prevents uncontrolled "float" of the forehead and eliminates the need for temporal struts. Follow-up time ranged from 6 to 60 months (mean = 2.6 years). There were no serious postoperative complications. Surgical results were good to excellent in 94% of cases and poor to fair in 6%. Only 1 patient with a Kleeblattschadel deformity required major revision, while another patient with trigonocephaly underwent a minor, extracranial recontouring procedure. Supraorbital rim and/or forehead recession suggestive of relapse or initial inadequacy of anterior projection occurred in 3 patients (17%). Residual, mild contour abnormalities of the forehead and/or temporal regions were found in 5 cases. To date, no gross disturbances in craniofacial growth related to our method of rigid fixation have been observed and no clinically detectable resynostosis has occurred. PMID- 1933928 TI - Ultrasound-guided aspiration of a neonatal brain abscess. AB - The authors successfully treated a Serratia marcescens brain abscess in the right parieto-occipital region of a newborn infant born at 27 weeks' gestation and weighing 800 g. Bedside ultrasound-guided aspiration techniques and local anesthesia were used to treat the abscess. PMID- 1933926 TI - Primary intracranial arachnoidal cysts. A study of 67 childhood cases. AB - Sixty-seven cases (41 males and 26 females) of arachnoidal cysts in children under 11 years are reported. About 53% of cases were diagnosed before 1 year of life. Thirty-one (42.2%) were supratentorial (interhemispheric 9, temporal fossa 10, convexity 5, sylvian fissure 3, supra- and/or retrosellar 4); 31 (46.2%) infratentorial (supra- and/or retrocerebellar 22, foramen of Magendie 3, quadrigeminal cistern 5, pontocerebellar 1); 5 (7.5%) supra- and infratentorial. Macrocephaly was the presenting symptom in 48 cases (71.5%). Associated features were frequent: cranial asymmetry in 24; aqueductal stenosis in 10; agenesis of corpus callosum in 8; deficient cerebellar lobullation in 4; Chiari I malformation in 2; neurofibromatosis type 1 with dysgenetic zones of the brain in 1; arteriovenous malformation in 1. Diagnosis was made at autopsy in six cases in the days before computed tomography and magnetic resonance: three patients had a cyst in the supra- and retrocerebellar midline; two had a cyst in the quadrigeminal cistern and the sixth was a rare case with the cyst passing from the posterior fossa to the left lateral ventricle through a hole in the basal surface of the brain. Small and some middle-sized cysts were not treated. Big and some middle-sized cysts were usually treated by cysto- and/or ventriculoperitoneal shunts. Arachnoidal cysts of the quadrigeminal cistern usually present with aqueductal stenosis and have to be treated with ventriculoperitoneal shunt. Craniotomy and fenestration of the cysts were performed in some cases with good results. The average mental level of these children is usually moderately low. PMID- 1933930 TI - Professor Nathan Sharon. PMID- 1933929 TI - Professor Toshiaki Osawa. PMID- 1933931 TI - From soybeans to lectins: a trail of research revisited. PMID- 1933932 TI - Interactions of five D-mannose-specific lectins with a series of synthetic branched trisaccharides. AB - The interaction of a series of synthetic, branched trisaccharides with five D mannose-specific lectins was studied by precipitation-inhibition assay. The branched methyl alpha-D-mannotrioside, alpha-D-Manp-(1----3)-[alpha-D-Manp-(1--- 6)]-alpha-D-Man pOMe, the best inhibitor of the Con A-Dextran interaction, was 42 times more potent than alpha-D-ManpOMe, and 3-6 times more potent than the two trisaccharides substituted with D-glucosyl groups, and 8-15 times those with D galactosyl groups. Surprisingly, methyl O-alpha-D-mannopyranosyl-(1----3)-alpha-D mannopyranoside was bound to Con A 8-fold more avidly than methyl alpha-D mannopyranoside. However, the related pea lectin (PSA) was singularly different from Con A in its carbohydrate-binding activity, showing no significantly enhanced binding to any of the sugars examined. The trisacchrides containing terminal, nonreducing, (1----3)-linked alpha-D-mannopyranosyl groups, i.e., alpha D-Manp-(1----3)-[alpha-D-Glep-(1----6)]alpha-D-Manp OMe, alpha-D-Manp-(1----3)] alpha-D-Galp-(1----6)]-alpha-D-ManpOMe++ +, and alpha-D-Manp-(1----3)-[alpha-D Manp-(1----6)]-alpha-D-Man pOMe, were the best inhibitors of the snowdrop lectin (GNA)-D-mannan precipitation system. On the other hand, all branched trisaccharides exhibited very similar inhibitory potencies toward the daffodil lectin (NPA)-D-mannan interaction, whereas alpha-D-Manp-(1----3)-[alpha-D-Galp-(1 ---6)]-alpha-D-ManpOMe++ + and alpha-D-Manp-(1----3)-[alpha-D-Manp-(1----6)] alpha-D-Man pOMe were somewhat better inhibitors than the other branched trisaccharides of the amaryllis lectin (HHA)-D-mannan precipitation reaction. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933933 TI - Malignant transformation in hepatocytes is associated with the general increase of glycoprotein ligands specifically binding to the endogenous lectin CSL. AB - Several hepatoma cell lines and hepatic ascite tumour cells were studied for the presence of glycoprotein ligands of an endogenous lectin, the "Cerebellar Soluble Lectin" (CSL). This lectin is also present in hepatocytes in vivo and in vitro and can be detected biochemically and immunologically. In transformed cells, the level of CSL glycoprotein ligands is increased 50-fold as compared to the control cells. Such an increase is not observed for the ligands of the plant lectin, concanavalin A, which is, as CSL, a D-mannose-binding lectin. These results indicated that the changes in glycans during malignant transformation, in these cells, is specifically important for minor glycans binding to CSL. PMID- 1933934 TI - Purification and characterization of the D-mannose receptor from J774 mouse macrophage cells. AB - Macrophages display on their cell surface a D-mannose-specific receptor which facilitates the scavenging of certain pathogens and deleterious macromolecules from the extracellular fluid as part of the host defense mechanism. The mouse D mannose receptor was purified from J774 E macrophages and an antiserum was generated against the receptor protein. In mouse macrophages, the newly synthesized receptor has an Mr of 157,000 Da and rapidly matures to a protein with an Mr of 172,000 Da. Both forms of the receptor protein are tightly associated with cell membranes. The receptor is found in a number of mouse macrophage cell types but is not present in mouse fibroblasts. An assay was developed to characterize D-mannose receptor-ligand binding based on immunoprecipitation of the detergent-solubilized receptor protein. The dissociation constant, determined for receptor and the neoglycoprotein D-mannose BSA, was 1.67nM. Receptor-ligand binding was calcium and pH dependent. Monosaccharides, such as D-mannose and L-fucose, partially inhibited receptor binding to the ligand D-mannose-BSA. PMID- 1933935 TI - Decreased biosynthesis of Forssman glycolipid after retinoic acid-induced differentiation of mouse F9 teratocarcinoma cells. Lectin-affinity chromatography of the glycolipid-derived oligosaccharide. AB - Glycolipids synthesized by the mouse teratocarcinoma F9 cells and F9 cells (RA/F9 cells) induced to differentiate by a 3-day treatment with 0.1 microM all-trans retinoic acid were analyzed. Both F9 cells and RA/F9 cells were incubated in media containing either D-[6-3H]galactose or D-[6-3H]glucosamine; the metabolically-radiolabeled glycolipids were isolated and the oligosaccharides were released from the glycolipids by ozonolysis and alkali fragmentation. From both cells, a single major pentasaccharide was isolated from the mixture of neutral [3H]oligosaccharides by affinity chromatography on a column of immobilized Helix pomatia agglutinin. The structure of this oligosaccharide was analyzed by methylation analysis and specific exoglycosidase treatments and identified as the Forssman pentasaccharide alpha-D-GalpNAc-(1----3)-beta-D GalpNAc-(1----4)-alpha-D-Galp-(1----4)-b eta-D- Galp-(1----4)-D-Glc. There was a 3-4-fold decreased amount of the Forssman pentasaccharide from RA/F9 cells relative to F9 cells. In contrast, there were no major differences between these cells in the levels of globoside, the precursor to Forssman glycolipid. To investigate the basis for the decline in Forssman glycolipid synthesis upon differentiation, the activity of UDP-D-Gal-NAc:GbOse4Cer alpha-(1----3)-N-acetyl D-galactosaminyltransferase (Forssman synthase) was determined in extracts of both the F9 and RA/F9 cells. The specific activity of Forssman synthase was approximately 70% lower in differentiated relative to the nondifferentiated cells. These data demonstrated that F9 cells synthesize authentic Forssman glycolipid, and that its expression and the activity of Forssman synthase were decreased following induced cellular differentiation. PMID- 1933936 TI - N-acetyllactosaminooligosaccharides that contain the beta-D-GlcpNAc-(1----6)-D Gal or beta-D-GlcpNAc-(1----6)-D-GalNAc sequences reveal reduction-sensitive affinities for wheat germ agglutinin. AB - Affinity chromatography of unreduced oligosaccharides on a small column of immobilized wheat germ agglutinin (WGA) revealed high-binding affinities for several radiolabeled molecules containing at the reducing end either beta-D GlcpNAc-(1----6)-D-Gal, beta-D-GlcpNAc-(1----6)-beta- D-Galp-(1----4)-D-GlcNAc, beta-D-GlcpNAc-(1----6)-beta-D-Galp-(1----4)DGlc, D-GlcpNAc-(1----3)-[beta-D GlcpNAc-(1----6)]-D-Gal, beta-D-GlcpNAc-(1----6)- D-GalNAc, or beta-D-Galp-(1--- 3)-[beta-D-GlcpNAc-(1----6)]-D-GalNAc sequences. Reduction changed the binding affinities remarkably: The sequences carrying a D-galactose or 2-acetamido-2 deoxy-D-galactose residue at the reducing end lost most of their affinities, but the sequences containing a D-glucose or 2-acetamido-2-deoxy-D-glucose residue at the reducing end gained additional affinity upon reduction. These findings emphasize the role of the unreduced, 6-o-substituted D-galactose and 2-acetamido 2-deoxy-D-galactose residues for the binding of saccharides to WGA, which has been recognized previously as a lectin specific for oligosaccharides containing a 2-acetamido-2-deoxy-D-glucose or sialic acid unit. The results suggested also that WGA-agarose chromatography of alditols may become a valuable method for the fractionation of oligo-N-acetyllactosaminoglycans and related saccharides. PMID- 1933937 TI - Intracellular pathway of a mucin-type membrane glycoprotein in mouse mammary tumor cells. AB - Epiglycanin, a mucin-type glycoprotein, was found by immunoelectron microscopy to be located in cytoplasmic compartments, as well as at the surface of the TA3-Ha mammary carcinoma ascites cell. The glycoprotein was identified by means of gold labeled secondary antibody bound to a primary anti-epiglycanin monoclonal antibody or by lectins specific for carbohydrate structures in epiglycanin. The primary antibody recognized a glycopeptide component containing a beta-D-(1----3) D-GalNAc chain attached to a serine or threonine residue. Two routes to the cell surface from epiglycanins's first-recognized location in the trans-Golgi reticulum were suggested. Its presence in vesicles, which fuse with the cell surface, would explain the presence of epiglycanin as an integral membrane protein. Some of these observed vesicles, however, may be endocytotic in character. Epiglycanin was also found in large multivesiculate sacs which were observed on occasion to be open to the extracellular milieu. This finding, as well as the observed fusion of small vesicles from the trans-Golgi network with the sacs, strongly suggested exocytotic migration for the large sacs. Endocytotic migration may also be possible, although incubation of viable cells with gold labeled antiepiglycanin antibody resulted in minimal uptake within the intracellular sacs, and incubation with [125I]-epiglycanin under metabolic conditions resulted in no detectable uptake of radiolabel by the cells. PMID- 1933938 TI - The glycosylation of glycoprotein lectins. Intra- and inter-genus variation in N linked oligosaccharide expression. AB - Glycosylated lectins represent a series of glycoproteins with related activities and, in the case of the Leguminosae, related amino acid sequences. Therefore, they offer a model system in which to study the diversity of N-linked oligosaccharide structures of plant glycoproteins. The influence of the polypeptide on the type of oligosaccharide substitution and the problem of inter- and intra-genus variation in glycosylation can also be addressed. Analysis of the glycosylation of 18 lectins has shown that they can be classified into four qualitatively similar groups on the basis of the Bio-Gel P-4 elution profiles of the oligosaccharides released by hydrazinolysis: (a) The Erythrina cristagalli profile, with a major component at 8.8 glucose units (gu) and minor components at 8.0, 7.2, and 5.8 gu. The major component is the heptasaccharide, alpha-D-Manp-(1 ---3)-[alpha-D-Manp-(1----6)]-[beta-D-Xyl p-(1----2)]- beta-D-Manp-beta-D-GlcpNAc (1----4)-[alpha-L-Fucp-(1----3)]- D-GlcNAc. (b) The Phaseolus vulgaris profile, which was characterized by peaks at 12.5, 11.7, 10.8, and 9.9 gu, in addition to the peaks at 8.8, 8.0, 7.2, and 5.8 gu mentioned above. These higher-mol.-wt. components were oligo-D-mannose oligosaccharides containing 9, 8, 7, and 6 D mannose residues, respectively. (c) The Lonchocarpas capassa profile, which had a major peak at approximately 8 gu. (d) The soybean agglutinin profile, which has a single peak at 12.5 gu. This peak consisted solely of an oligomannose undecasaccharide containing 9 D-mannose residues. This lectin is unique in that it shows no microheterogeneity. PMID- 1933939 TI - Application of lectin histochemistry and carbohydrate analysis to the characterization of lysosomal storage diseases. AB - In lysosomal storage diseases that involve a defect in the catabolism of glycoconjugates, lectin histochemistry adds a new dimension to the characterization of stored carbohydrates as it identifies sugar residues in situ in the affected cells and, thus, determines which cell types are affected by storage. It may be combined with chemical and biochemical analysis by h.p.l.c. The present review summarizes recent results for a variety of storage diseases and presents new data for GM1-gangliosidosis. PMID- 1933940 TI - A T-antigen-binding lectin from Channa leucopunctatus (Murrel) plasma. AB - The plasma of Channa leucopunctatus, which agglutinates human A,B,O blood-group erythrocytes nonspecifically, contains three separate agglutinating activities that are distinguishable by hemagglutination with specific blood-group erythrocytes. Blood group A agglutinating activity of the plasma was separated from the other two hemagglutinating activities by DEAE-cellulose column chromatography and further purified to homogeneity by affinity chromatography on 2-acetamido-2-deoxy-D-galactose coupled to epoxy-activated Sepharose 6B. The apparent homogeneity of the lectin was established by poly(acrylamide) gel electrophoresis, isoelectric focusing, immunodiffusion, and cross immunoelectrophoresis. The native protein has a mol. wt. of 140,000 and two identical subunits. The isoelectric point of the affinity-purified lectin is 4.6. Amino acid analysis indicated high proportions of glycine, alanine, and aspartic acid. The lectin is a glycoprotein and it has a requirement for divalent cations, Ca2+ and Mg2+ or Mn2+, for hemagglutinating activity. 2-Acetamido-2-deoxy-D galactose, 4-nitrophenyl 2-acetamido-2-deoxy-alpha-D-galactopyranoside, T antigenic disaccharide, and Forssman glycolipid are potent inhibitors. PMID- 1933941 TI - The (1----3)-linked alpha-L-fucosyl group of the N-glycans of the Wistaria floribunda lectins is recognized by a rabbit anti-serum. AB - An increasing number of plant glycoproteins have been shown to possess a characteristic N-glycan component containing a beta-(1----2)-linked D-xylose unit on the core beta-D-mannose unit, and an alpha-(1----3)-linked L-fucose unit on the asparagine-linked 2-acetamido-2-deoxy-D-glucose unit. Wistaria floribunda seeds have two distinct lectins; the erythroagglutinin, WFA, and the lymphocyte mitogen, WFM. Earlier studies indicated that both lectins belong to such a class of glycoproteins. We now report the complete structural analysis of Pronase glycopeptides derived from WFA. On the basis of chemical treatment of the glycopeptides, carbohydrate composition and methylation analysis of fluorescein labeled glycopeptides, and their susceptibility to specific exoglycosidases, the structure of the WFA glycan was found to be, alpha-D-Manp-(1----6)-[beta-D-Xylp (1----2)]- [alpha-D-Manp(1----3)]-beta-D-Manp-(1----4)-beta-D-GlcpNAc-[ alpha-L- Fucp-(1----3)]-beta-D-Glcp-NAc-(1----N). Quantitative studies on the interaction of the original fluorescein-labeled glycopeptide and its specific degradation products with a rabbit anti-glycan antibody, developed against WFM, showed that the (1----3)-linked alpha-L-fucose unit is essential for interaction. Loss of the terminal alpha-D-mannosyl groups resulted in decreased, though detectable binding. PMID- 1933943 TI - Changes in the expression of lectins in human T lymphocyte membrane upon mitogenic stimulation. AB - Surface lectins, specific for given sugar structures, are expressed on human T cells, as shown by flow cytofluorometry using F-neoglycoproteins bearing either beta- and alpha-D-galactosyl, beta-D-galactosyl 6-phosphate, or alpha-L-rhamnosyl groups, but not by F-neoglycoproteins bearing other sugar groups (such as alpha-D mannosyl groups). After stimulation with Phaseolus vulgaris mitogen, the number of cells that bind beta-D-galactosyl 6-phosphate groups (6-P-beta-D-Galp lec+ cells) increased fourfold during the first five days; these cells are helper (CD4+) T cells. Conversely, cells that bind alpha-L-Rha groups belong to the T suppressor (CD8+) family and their number moderately increased. Upon stimulation by concanavalin A, the number of cells expressing the lectin recognizing alpha-L Rha groups increased during the first two days and then decreased within the next two days. These results are discussed with regard to the implication of lymphocyte membrane lectins in the suppressor mechanism and in the homing process. PMID- 1933942 TI - Purification and characterization of Canavalia gladiata agglutinin. AB - A lectin from Japanese jack bean (Canavalia gladiata agglutinin, CGA) was purified by affinity chromatography on a maltamyl-Sepharose column. On sodium dodecyl sulfate-poly(acrylamide) gel electrophoresis, CGA was shown to have a protein subunit with a mol. wt. of 30,000. CGA has an amino acid composition similar to that of Concanavalin A. The lectin activity of CGA could be detected not only by hemagglutination assay with trypsinized human erythrocytes but also by the binding assay with intact horseradish peroxidase. The binding method could determine CGA in a concentration ranging from 50 to 500 ng/mL. The quantitative inhibition studies of the binding indicated that CGA has sugar-binding specificities similar to those of concanavalin A. PMID- 1933945 TI - Synthesis and carbohydrate-binding activity of poly(ethyleneglycol)-Ricinus communis agglutinin I conjugates. AB - The synthesis of poly(ethyleneglycol) (PEG)-lectin conjugates was investigated to provide new reagents for evaluation as biological response modifiers. PEG was activated with 1,1'-carbonyldiimidazole (CDI), followed by conjugation with Ricinus communis I (RCAI) lectin. The resulting conjugates were heterodisperse with respect to molecular weight. Carbohydrate-binding activity was retained. The conjugates were separated by affinity chromatography into fractions differing in apparent carbohydrate-binding affinity. Conjugation of RCAI with PEG 4 (mol.wt. 3350) or PEG 6 (mol.wt. 8000) appeared to provide less hindrance of the lectin binding site compared to conjugates prepared with PEG 20 (mol.wt. 20,000). Results of free amine assays indicated that higher ratios of PEG to RCAI in conjugates correlated with loss of low-affinity binding and retention of high affinity binding. The data showed the feasibility of preparing PEG-lectin conjugates for in vivo use. PMID- 1933944 TI - Studies of the binding specificity of the soluble 14,000-dalton bovine heart muscle lectin using immobilised glycolipids and neoglycolipids. AB - The aim of the present study has been to investigate the binding specificity of the soluble 14,000-dalton lectin of bovine heart muscle towards immobilised oligosaccharides in clustered form. To this end, chromatogram overlay assays and quantitative plastic-microwell-binding assays have been performed using several natural glycolipids and neoglycolipids containing one or more of the disaccharide units, beta-D-Galp-(1----4 or 3)-D-GlcNAc or beta-D-Galp-(1----4)-D-Glc and related structures. The microwell assay gave the most consistent results. It was observed that for binding by the soluble lectin the optimal sequence, which is beta-D-Galp-(1----4 or 3)-D-GlcNAc, must occur at the nonreducing end of longer oligosaccharides when linked to lipid. These oligosaccharides may be of poly(N acetyllactosamine) type or they may be mono- or multi-antennary, complex-type chains in which the disaccharide is joined directly to a trimannosyl core. The lectin bound to such immobilised lipid-linked oligosaccharides on which the terminal D-galactosyl groups are substituted with alpha-L-Fucp-(1----2), alpha-D Galp-(1----3), or alpha-NeuAc-(2----3) groups. However, no binding was detected if the terminal D-galactosyl groups were substituted with an alpha-NeuAc-(2----6) group or the subterminal N-acetylglucosamine units with an alpha-L-Fucp-(1----3 or -4) group. Internally located N-acetyllactosamine units where the D-galactose units are disubstituted by beta-D-GlcNacp-(1----3) and -(1----6) units, as in branched poly(N-acetyllactosamine) backbones were not bound by the bovine lectin. These results are in accord with previous observations on the bovine lectin and the corresponding human and rat lectins, using structurally defined oligosaccharides as inhibitors of binding. The results of comparative binding experiments using paragloboside and ceramide hexasaccharide which contain one and two N-acetyllactosamine units, respectively, joined in linear sequence to the lactosylceramide core, were equivocal with respect to the availability of the internal N-acetyllactosamine units for binding by the bovine lectin. PMID- 1933946 TI - Binding of hydroxylysine-linked saccharides by galaptin, a galactoside-binding animal tissue lectin. PMID- 1933947 TI - Sandwich enzyme-linked immunosorbent assay of D-mannans of Candida albicans NIH A 207 and NIH B-792 strains using concanavalin A and polyclonal rabbit anti-C. albicans antisera. PMID- 1933948 TI - The D-galactose-inhibitable lectin of Entamoeba histolytica. PMID- 1933949 TI - Fluorescein-labeled O-glycosyloxyalkenyl-aminoalkenyl-acrylamide copolymers in lectin-saccharide binding studies. PMID- 1933950 TI - Purification in large amounts of beta-D-galactoside-binding lectins from a murine thymic epithelial cell line. PMID- 1933951 TI - Differences in the amount of N-acetyl- and N-glycoloyl-neuraminic acid, as well as O-acylated sialic acids, of fetal and adult bovine tissues. PMID- 1933952 TI - Lactose-binding lectin expression in human colorectal carcinomas. Relation to tumor progression. AB - Lactose-binding lectins having Mr values of approximately 14,000 (L-14.5) and approximately 35,000 Da have been found in a variety of vertebrate tissues, including normal intestine and colon, and in several types of tumors such as colon carcinomas. To determine the clinical relevance of such lectins in human colon cancer, specimens from 46 patients with colorectal carcinoma of identified Dukes' stages were selected and analyzed for the presence and amount of lactose binding lectins by immunoblotting using a polyclonal, rabbit anti-lectin antibody followed by binding of 125I-labeled anti-rabbit IgG. The amount of a lectin having an Mr value of approximately 31,000 Da (L-31) varied among the specimens. The levels of L-31 lectin in colorectal cancer specimens from primary tumors of patients with distant metastases (Dukes' stage D) were significantly higher than were those from patients without detectable metastases (Dukes' stages B1 and B2). In contrast, among the various specimens the variation in the level of the L-14.5 lectin was smaller, and there was no correlation between the amount of this lectin and cancer stage. Immunohistochemical staining of thin sections of colorectal tumor specimens using antibodies specific for either L-31 or L-14.5 lectin revealed that the two were located at different places, the L-31 lectin primarily within the cytoplasm of carcinoma cells, and the L-14.5 lectin associated with secreted material. These results indicated that the relative amount of the L-31 lectin increases as the colorectal cancer progresses to a more malignant stage. PMID- 1933953 TI - Further characterization of the saccharide specificity of peanut (Arachis hypogaea) agglutinin. AB - 2-Dansylamino-2-deoxy-D-galactose (GalNDns) has been shown to bind to peanut (Arachis hypogaea) agglutinin (PNA) in a saccharide-specific manner. This binding was accompanied by a five-fold increase in the fluorescence of GalNDns. The interaction was characterized by an association constant of 0.15 mM at 15 degrees and delta H and delta S values of -57.04 kJ.mol-1 and -118.1J.mol-1.K-1, respectively. Binding of a variety of other mono-, di- and oligo-saccharides to PNA, studied by monitoring their ability to dissociate the PNA GalNDns complex, revealed that PNA interacts with several T-antigen-related structures, such as beta-D-Galp-(1----3)-D-GalNAc, beta-D-Galp-(1----3)-alpha-D-GalpNAcOMe, and beta D-Galp-(1----3)-alpha-D-GalpNAc-(1----3)-Ser, as well as the asialo-GM1 tetrasaccharide, with comparable affinity, thus showing that this lectin does not discriminate between saccharides in which the penultimate sugar of the beta-D Galp-(1----3)-D-GalNAc unit is the alpha or beta anomer, in contrast to jacalin (Artocarpus integrifolia agglutinin), another anti T-lectin which preferentially binds to beta-D-Galp-(1----3)-alpha-D-GalNAc and does not recognize beta-D-Galp (1----3)-beta-D-GalNAc or the related asialo-GM1 oligosaccharide. These studies also indicated that, in the extended combining region of PNA which accommodates a disaccharide, the primary subsite (subsite A) is highly specific for D-galactose, whereas the secondary subsite (subsite B) is less specific and can accommodate various structures, such as D-galactose, 2-acetamido-2-deoxy-D-galactose, D glucose, and 2-acetamido-2-deoxy-D-glucose. PMID- 1933954 TI - Interactions of concanavalin A with glycoproteins. A quantitative precipitation study of concanavalin A with the soybean agglutinin. AB - Certain oligomannose-type glycopeptides have been previously shown to be bivalent for binding to concanavalin A and capable of precipitating the lectin by forming homogeneous cross-linked lattices [L. Bhattacharyya, M. I. Khan, and C.F. Brewer, Biochemistry, 27 (1988) 8762-8767]. In the present study, the effect of protein environment on the binding properties of an oligomannose-type oligosaccharide has been examined through quantitative precipitation analysis of the interactions of concanavalin A (Con A) with the soybean (Glycine max) agglutinin (SBA), which is a tetrameric glycoprotein possessing a single Man9-oligomannose chain per monomer. The results showed that SBA forms two different types of cross-linked complexes with tetrameric Con A, depending on the relative ratio of the two molecules in solution. At a concentration of one equivalent or less, SBA forms a 1:1 complex with Con A. At concentrations exceeding one equivalent, SBA forms a 2:1 complex with Con A. However, SBA forms only 1:1 cross-linked complexes with dimeric forms of Con A, such as acetyl- and succinyl-Con A. The results demonstrated that the total valency of the carbohydrate of SBA is a function of both the quaternary structure of Con A, as well as the relative ratio of SBA to Con A. In addition, the individual Man9-oligosaccharide, which as a glycopeptide is bivalent for binding to Con A, expresses univalency when present on the protein matrix of SBA. PMID- 1933955 TI - Isolation and characterization of a seed lectin from elderberry (Sambucus nigra L.) and its relationship to the bark lectins. AB - A third elderberry (Sambucus nigra L.) lectin (SNA-III) has been isolated from dry seeds by affinity chromatography on immobilized 2-acetamido-2-deoxy-D galactose. This lectin is a blood-group, nonspecific glycoprotein containing 21% of carbohydrate, and is rich in asparagine (or aspartic acid), serine, glutamine (or glutamic acid), and glycine. Gel filtration on Superose 12 yielded a single symmetrical peak corresponding to mol. wt. 50,000, SDS-poly(acrylamide) gel (SDS PAGE) electrophoresis showed a single polypeptide band of 33 kDa, indicating that the native protein is a dimer of identical subunits. Hapten-inhibition assays of the agglutination of red blood cells showed that 2-acetamido-2-deoxy-D-galactose is the best inhibitor, being twice as potent as D-galactose, melibiose, and 2 amino-2-deoxy-D-galactose. A comparison of SNA-III to the previously described elderberry-bark lectins, SNA-I and SNA-II, indicated that the seed lectin is well distinct from them. PMID- 1933956 TI - Characterization and isolation of an intracellular D-mannose-specific receptor from human promyelocytic HL60 cells. AB - Most mammalian macrophages express D-mannose-specific receptor (membrane lectin, Mr 175,000) allowing endocytosis of their ligands, but cells of the monocytic lineage (HL60, U937, monocyte) lack this receptor. However, after permeabilization, promyelocytic, promonocytic cells and monocytes bound fluoresceinylated D-mannose-terminated neoglycoproteins as evidenced by flow cytometry. Under these conditions, confocal analysis confirmed the intracellular membrane localization of the labeling and the absence of nuclear binding. An intracellular D-mannose-specific receptor was isolated from the human promyelocytic cell line HL60, by affinity chromatography on 4 isothiocyanatophenyl alpha-D-mannopyranoside-substituted Affi-gel as a 60,000-Mr membrane protein requiring divalent cations for the ligand binding. Under the same conditions, mouse macrophages were shown to express a 175,000-Mr D-mannose specific receptor but not the 60,000-Mr receptor. PMID- 1933957 TI - [From the viewpoint of fathers. From paternalism to paternity in service, organizational and pedagogical relations]. PMID- 1933958 TI - [Cardiac metabolism in patients with insulin-dependent diabetes without coronary atherosclerosis]. AB - Eleven insulin-dependent diabetic patients (IDDM) with angiographically normal coronary arteries and normal echocardiographic dipyridamole test, and 12 normal controls were studied at rest and after atrial pacing. Simultaneous sampling from arterial and coronary sinus blood was performed. In IDDM patients, despite hyperglycemia, myocardial glucose uptake was slightly lower than in controls. This process was significantly activated in both groups by atrial pacing. The isotopically calculated net flux of lactate across myocardium, in agreement with the net balance value based on unlabeled lactate-pyruvate arterio-venous differences, showed a net uptake in controls (3.5 +/- 0.6 mumol/min/1.73 m2) and a net release in IDDM (12.4 +/- 2.6; p less than 0.01). Atrial pacing stimulated lactate uptake in both groups. Myocardial uptake of ketone bodies was significantly higher in IDDM than in controls (37.0 +/- 6.3 mumols/min/1.73 m2 vs 10.1 +/- 3.4; p less than 0.01). Free fatty acid uptake was also significantly greater in IDDM than in controls (44.1 +/- 7.0 mumols/min/1.73 m2 vs 24.1 +/- 5.1; p less than 0.01). Alanine and branched chain amino-acids were released by diabetics but not by control hearts at rest. The normalization of blood glucose concentrations restored normal patterns of lactate and ketone body kinetics across diabetic myocardium. IN CONCLUSION: at rest, myocardial lactate and aminoacids uptake is markedly impaired in IDDM without coronary artery disease; the metabolic abnormalities of the diabetic myocardium is not a primary phenomenon but rather a consequence of hypoinsulinemia and hyperglycemia because insulin administration, resulting in normoglycemia, restored normal patterns of cardiac metabolism. PMID- 1933959 TI - [Identification of viable myocardium in patients with chronic ischemic disease and left ventricular dysfunction: correlations between blood flow, metabolic activity and regional function]. AB - To identify the presence of viable myocardium in areas of severe systolic dysfunction, we studied 22 patients (age 45 to 78 years) with chronic coronary artery disease and left ventricular dysfunction (mean ejection fraction 29 +/- 9%). All subjects underwent thallium-201 single photon emission computed tomography (SPECT), using the reinjection technique, positron emission tomography (PET) with H2(15)O and 18-fluorodeoxyglucose (FDG) to measure regional blood flow and exogenous glucose uptake, respectively, and nuclear magnetic resonance imaging (MRI). From matched transaxial PET, SPECT and MRI tomograms, a total of 290 left ventricular myocardial regions were analyzed. According to the regional wall thickening, measured from MRI, 3 groups of myocardial regions were identified: akinetic-dyskinetic (n = 60), showing either absence of systolic thickening or systolic thinning; hypokinetic (n = 97), showing an absolute wall thickening less than or equal to 2 mm; normal (n = 133), showing an absolute wall thickening greater than 2 mm. Of the 60 akinetic or dyskinetic regions, 3 were normal by SPECT and 37 corresponded to either a total or partially reversible thallium defect: 34 of these 40 regions also showed presence of FDG uptake by PET. The remaining 20 akinetic or dyskinetic regions showed a thallium defect that remained irreversible after reinjection: in 7 of these 20 regions, however, there was evidence of metabolic activity, as expressed by FDG uptake. Thus, 47 (78%) of the myocardial akinetic or dyskinetic regions showed presence of viable tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933960 TI - [Syndrome X: a long story so far without end]. PMID- 1933961 TI - [Isolated cardiac myocytes: preparation and use in experimental cardiology]. PMID- 1933962 TI - Ventricular late potentials in the assessment of mitoxantrone cardiotoxicity. AB - Sixteen female patients underwent signal-averaged electrocardiography and radionuclide angiography for the assessment of the resting left ventricular ejection fraction in the course of chemotherapy with mitoxantrone (MTX) for advanced breast cancer. Nine patients had received prior cardiotoxic treatments. Our findings indicate that patients treated with MTX may develop late potentials. PMID- 1933963 TI - Right ventricular aneurysm: a new prognostic indicator after a first acute myocardial infarction. AB - The prognostic implication of a right ventricular aneurysm after a first acute myocardial infarction (AMI) was assessed on a series of 137 AMI patients 12 of whom had a right ventricular aneurysm detected at radionuclide angiocardiography. The follow-up lasted 36 months. Mortality was 50 and 18.4% in patients with and without right ventricular aneurysm, respectively (p less than 0.02). Groups did not differ in age, male-to-female ratio, AMI site, left ventricular ejection fraction (LVEF), peak filling rate (PFR), left ventricular size. A multivariate logistic analysis showed that only three out of ten clinical and functional variables qualified to be independent predictors of death: right ventricular aneurysm (odd ratio = 2.48, confidence limits = 1.21-4.98), LVEF less than 52% (odd ratio = 1.91, confidence limits = 1.03-3.48), abnormal terminal P wave forces (odd ratio = 1.72, confidence limits = 1.07-2.75). The analysis of single case histories did not provide a clue to clarify the reasons accounting for the negative prognostic implication of a right ventricular aneurysm. In conclusion, a significant positive relationship between right ventricular aneurysm and mortality after AMI has been demonstrated; further study is needed to clarify the relevant mechanisms. PMID- 1933964 TI - Effect of a media campaign to reduce delay times for acute myocardial infarction on the burden of chest pain patients in the emergency department. AB - We evaluated the effect of a media campaign aimed at reducing delay times in suspected acute myocardial infarction (AMI) on the volume of chest pain patients seen in the emergency department. During the 1st week of the campaign, the mean number of chest pain patients increased from 10.5 per day prior to the start to 25.4. However, the number declined rapidly in subsequent months. The greatest increase was observed in patients with chest pain in whom AMI was not suspected on examination. During the campaign, 4,805 patients with chest pain appeared in the emergency department as compared with 4,407 patients during the same time period prior to its start, an increase of 9%. The number of patients with confirmed AMI increased from 595 to 629 (6%). PMID- 1933965 TI - Left ventricular intramyocardial rhabdomyoma suggested by coronary angiography. AB - Coronary angiography, left ventriculography, and magnetic resonance imaging (MRI) indicated that a 45-year-old male with a left ventricular intramyocardial tumor had adult type rhabdomyoma. The tumor was in the lateral wall of the left ventricle, making catheter biopsy unfeasible. Because the undeveloped tumor does not project into the cavity of his left ventricle, the patient had no symptoms. Angiography and MRI are beneficial in diagnosing intramyocardial tumors which other methods do not confirm. PMID- 1933966 TI - Diagnosis of an aorto-caval fistula by echo 2D color Doppler flow imaging and echocardiographic probe. AB - We describe a clinical case presenting two unusual features. The first was a spontaneous aorto-caval fistula which had developed from rupture of an atherosclerotic aortic aneurysm into the inferior vena cava. The second uncommon feature depended on the unusual method by which the diagnosis was performed. In fact, using an echo-Doppler color flow (HP 77020A ultrasound system) with a 2.5 MHz echocardiographic probe abdominal examination revealed an aneurysm of the abdominal aorta that communicated with a dilated inferior vena cava. Furthermore, flow study with pulsed color Doppler revealed a continuous turbolent, mixed (arterial and venous) blood flow into the vena cava. PMID- 1933967 TI - Diffuse aortitis complicating Behcet's disease leading to severe aortic regurgitation. AB - Cardiovascular complications are uncommon in Behcet's disease, but are frequently the cause of morbidity and mortality. Venous and peripheral arterial involvement have been well documented, but involvement of the proximal aorta has rarely been described. This report details a Chinese patient with Behcet's disease. Diffuse aortitis led to proximal aortic dilatation and severe aortic regurgitation necessitating aortic valve replacement. Histopathology of the aorta revealed features similar to those observed in other systemic diseases with aortic involvement. PMID- 1933968 TI - Successful emergency percutaneous balloon mitral valvotomy in a patient with massive left atrial thrombosis: utility of transesophageal echocardiographic monitoring. AB - Emergency percutaneous balloon mitral valvotomy was carried out successfully in a 65-year-old woman with severe mitral stenosis and massive left atrial thrombosis. Transesophageal echocardiography was of great value in monitoring each step of the procedure in order to avoid systemic embolization due to improper manipulation of the dilating apparatus within the left atrium. PMID- 1933969 TI - Educating the population at risk. PMID- 1933970 TI - Blood pressure and sleep apnea: results of long-term nasal continuous positive airway pressure therapy. AB - Arterial blood pressure patterns in 12 men with sleep apnea and arterial hypertension were studied at baseline and after 6 months' therapy with nasal continuous positive airway pressure (nCPAP). Preexisting antihypertensive medication was discontinued 1 week before baseline measurements. Weight did not change during the study period; body mass index was 29.3 (range, 25.4-38.5) vs. 29.3 (25.0-38.5). During therapy the apnea index decreased from 58 (range 30-73) to 2 (range 0-7) apneic episodes per hour (p less than 0.01). Intra-arterial systolic (BP sys.) and diastolic (BP dias.) blood pressure and heart rate decreased during therapy (p less than 0.001). Mean values +/- 95% confidence intervals were as follows: BP sys., 147.1 (+/- 1.6) mm Hg vs. 126.4 (+/- 1.5) mm Hg; BP dias., 81.6 (+/- 0.8) mm Hg vs. 69.4 (+/- 0.6) mm Hg; heart rate, 68.8 (+/ 0.7) beats/min vs. 65.4 (+/- 0.7) beats/min. Furthermore, the variability of these parameters decreased during therapy: variability BP sys., 53.8 (+/- 1.1) mm Hg vs. 25.6 (+/- 1.1) mm Hg; variability BP dias., 35.6 (+/- 0.7) mm Hg vs. 17.9 (+/- 0.7) mm Hg; variability of heart rate, 28.1 (+/- 0.7) beats/min vs. 14.9 (+/ 0.7) beats/min (p less than 0.001). During treatment we found that blood pressure scores already dropped during the awake phase, with a further decrease during non-REM and REM sleep (p less than 0.001). Our results, which demonstrate the reversibility of high blood pressure upon treatment of sleep apnea, indicate that sleep apnea can be an etiological factor in hypertension. Sleep apnea should therefore be considered in the differential diagnosis of arterial hypertension. PMID- 1933971 TI - The natural course of cardiac conduction disturbances in myotonic dystrophy. AB - In this study we noninvasively followed for a mean period of 46 months 21 patients with different grades of myotonic dystrophy to evaluate the course of the involvement of the cardiac conducting system. Six patients (28.6%), 1 affected by a mild and 5 by a severe form of the neuromuscular disorder, showed appearance or deterioration of conduction disturbances suggesting a serious derangement of the specialized tissue; in 3 of them a permanent demand pacemaker was implanted. Conduction defects are the most frequent cardiac manifestations in myotonic dystrophy and become worse with time, mainly in patients with higher degrees of the disease. Furthermore, first-degree atrioventricular block may represent an early sign of developing of more advanced conduction defects. PMID- 1933972 TI - Anticardiolipin antibody and stroke: possible relation of valvular heart disease and embolic events. AB - To establish the etiology of strokes related to the anticardiolipin antibody (Acla) syndrome and to determine the relationship of valvular heart disease and stroke in the presence of the Acla, clinical and objective characteristics of 21 patients with Acla, focal cerebral ischemic events were retrospectively analyzed. Twelve (86%) of 14 patients with stroke and 3 (42%) of 7 patients with non-stroke cerebral ischemic events had echocardiographic evidence of left-sided valvular abnormalities. Features characteristic of cardioembolic stroke were present in 12 (86%) of the 14 patients with stroke. The strength of the association between valvular disease and stroke, combined with the clinical and radiologic features noted, suggest that strokes related to the Acla syndrome typically are embolic, from a cardiac source. PMID- 1933973 TI - The interventional radiologist--fellowship training. PMID- 1933975 TI - Use of an intravascular endoprosthesis (stent) to establish and maintain short term patency of the ductus arteriosus in newborn lambs. AB - The feasibility of stenting the ductus arteriosus with a balloon-expandable vascular endoprosthesis was tested in 8 newborn lambs. Tantalum wire and stainless steel mesh coronary stents were implanted antegrade or retrograde by percutaneous transfemoral catheterization. One lamb died during the procedure from perforation of the aorta. In 7 lambs, the ductus arteriosus was crossed using endhole catheters and wires, and stents mounted on angioplasty catheters were expanded in the ductus arteriosus. Six lambs had successful implantation and had maintained a sizeable patent ductus arteriosus at 2 h. We conclude that the feasibility of percutaneous stenting of the newborn ductus was demonstrated. By providing patency of the ductus arteriosus, stents may offer nonsurgical alternatives for palliation of cyanotic congenital heart disease and hypoplastic left heart syndrome. PMID- 1933974 TI - Interventional procedures in the upper urinary tract. AB - The introduction and acceptance of percutaneous nephrostomy as a safe and effective alternative to surgical nephrostomy served as the impetus for the development and expansion of an ever-increasing number of techniques that are encompassed by the term "interventional uroradiology." This article reviews many of the nonvascular interventional techniques that have proliferated during the past decade and that are currently used in the kidney, ureter, and perinephric space. The authors emphasize those procedures that are most frequently employed, as well as their own preferences and perspectives on these procedures. PMID- 1933976 TI - Myocardial abscess resulting in a pseudoaneurysm: case report. AB - This report describes the diagnostic workup of a case of a pseudoaneurysm of the heart resulting from Staphylococcal pericarditis and/or abscesses of the myocardium. The pericardial effusion and myocardial abscesses were detected on 2D echocardiography and computed tomography. The resulting pseudoaneurysm could be demonstrated on magnetic resonance imaging and color Doppler ultrasound, and confirmed by left ventriculography. Color-encoded Doppler ultrasound alone would have provided the definitive diagnosis of the aneurysm. PMID- 1933977 TI - Embolotherapy for small bowel hemorrhage from metastatic renal cell carcinoma: case report. AB - Embolization for control of hemorrhage in the small bowel carries a significant risk of bowel infarction. A case is presented where severe gastrointestinal hemorrhage from a hypervascular renal cell carcinoma metastasis to the jejunum was effectively controlled by superselective embolization of mesenteric tumor supply arteries with Gelfoam particles. Adjacent normal mesenteric arteries remained open. It is concluded that in specific instances where direct mesenteric feeders to a tumor can be catheterized, such embolization can be performed safely. PMID- 1933978 TI - Milk of calcium pericardial effusion: case report. AB - A patient with milk of calcium (MOC) pericardial fluid secondary to radiation therapy is presented. We have been unable to identify a previous report of MOC pericardial fluid. PMID- 1933980 TI - Mainframing dentistry. The marginal care risk and reevaluation model. PMID- 1933979 TI - Women with coronary heart disease: an application of Roy's Adaptation Model. PMID- 1933981 TI - An alginate pick-up alternative to the altered cast technique. AB - The altered cast technique for distal extension removable partial dentures involves such cumbersome laboratory procedures that many dentists avoid using it. This article presents a simple and easy clinical technique that accomplishes the same objective, but involves no additional laboratory work. In addition, the technique provides superior accuracy when compared with the altered cast technique. PMID- 1933982 TI - Rational tooth preparation for porcelain laminate veneers. PMID- 1933983 TI - Diabetes mellitus and periodontal disease. AB - One of the most commonly reported oral manifestations of diabetes mellitus is the increased prevalence and severity of periodontal disease. Whereas the periodontal disease of the diabetic patient is clinically similar to that found in nondiabetic individuals, the condition appears to be more severe and poses very serious health problems for the diabetic patient. This article will review the current state of knowledge concerning the relationship of diabetes mellitus to periodontal disease, and will examine the reported incidence and etiology of periodontal disease in the diabetic patient. PMID- 1933984 TI - Amyloidosis of the oral cavity: report of five cases. AB - Five cases of amyloidosis involving structures in the oral cavity are reported. Three cases appeared to be secondary systemic amyloidosis, one case was the systemic form associated with multiple myeloma, and one case appeared to represent nodular or localized amyloidosis. All cases appeared in persons over 63 years of age, and the most common area of involvement was the tongue. The nature of so-called amyloid deposits in certain odontogenic tumors is discussed in light of recent knowledge of amelogenins and enamelins. PMID- 1933985 TI - Galvanic action: a case report. AB - The presence of two dissimilar metals in the mouth acting as electrodes, with saliva serving as an electrolyte, can generate an intraoral electric current known as galvanic action. The result of these circuits is usually a transient, unpleasant feeling in the mouth, but occasionally other tissues in the body can be affected. This article presents a report of a patient with a presumable galvanic action that began with the insertion of orthodontic appliances and developed into a serious, debilitating illness. PMID- 1933986 TI - An added treatment modality for pyogenic granuloma. AB - This article presents the history of a case of pyogenic granuloma. The authors describe the lesion, its excision, and an additional treatment modality of doxycycline 100 mg daily for 20 days. PMID- 1933987 TI - Tooth preparation for full-coverage restorations using the enamel milling technique. AB - There are many acceptable methods of tooth preparation for full-coverage restorations. The technique used should be systematic, with step-by-step procedures to produce an easily followed routine. This will minimize undesirable, haphazard tooth reduction. The technique presented in this paper is a simple, exacting, and conservative method of tooth reduction, requiring a minimum of instrumentation. PMID- 1933988 TI - Comprehensive treatment for a subcrestal fractured incisor in the mixed dentition. AB - This case report describes the treatment of a transversely fractured developing permanent central incisor in the mixed dentition of a 9-year-old patient. A comprehensive approach was followed combining endodontics, orthodontics, prosthodontics, and periodontics to maintain arch integrity and alleviate the need for tooth replacement by a fixed or removable prosthesis. PMID- 1933989 TI - Osseointegrated implants with an intramobile element in the treatment of edentulous jaws. AB - Edentulous patients have demonstrated impaired masticatory ability with conventional dentures. The masticatory deficiency is due, in part, to the instability of the mandibular denture and the lack of proprioception of conventional dentures. The Interpore IMZ implant offers an intramobile element in the design that may enhance proprioception of screw-retained dentures. The following case reports evaluated the stability and patient response of 10 edentulous patients who received a screw-retained denture with the intramobile element. The results indicated that the IMZ system can be successfully incorporated in this design. PMID- 1933990 TI - Differential diagnosis of oral mucosal petechial hemorrhages. AB - Petechiae are pinpoint hemorrhages that occur in subcutaneous or submucosal tissues in a wide variety of conditions. Because of their diversity, the differential diagnosis of oral mucosal petechial hemorrhages is complex. The authors report a case of palatal petechial hemorrhages secondary to episodes of intense vomiting. A review of the many disorders underlying petechial hemorrhages is based on etiologic factors including trauma, platelet abnormalities, clotting factor deficiencies, and defects in vascular integrity. PMID- 1933991 TI - Liability in the failure to recognize TMJ disorders. PMID- 1933992 TI - Your curriculum vitae, your resume, and you. PMID- 1933993 TI - Improving medication compliance: a review of selected issues. AB - The impact of various factors on patient compliance with prescribed therapy was determined from a review of the relevant literature. Complexity of treatment regimen was found to be directly related to noncompliance as well as to increased use of health-care services. Accordingly, physicians, pharmacists, and health care administrators are urged to develop formulary recommendations in light of potential effects on patient well-being and aggregate health-care expenditures. The development of institutional initiatives (clinical protocols) for pharmaceuticals are also urged, to give physicians greater access to therapeutic options with which to reduce patients' regimen complexity. Finally, the adoption of a team-management approach in the treatment of chronic disease and the implementation of interactive health-education programs, such as pharmacy-based medication utilization review, are advocated, as measures that have been shown to increase both the continuity and quality of patient care. PMID- 1933994 TI - Ofloxacin in the treatment of uncomplicated gonorrhea and chlamydial genital infection. AB - The subjects were 149 patients (96 men, 53 women) with gonorrhea only (n = 66), chlamydial infection only (n = 48), or both gonorrhea and chlamydial infection (n = 35). All patients with gonorrhea were culture positive; all isolates cultured before treatment were sensitive to ofloxacin. Chlamydial infection was diagnosed by culture, inclusions being identified by indirect immunofluorescence. The patients with gonorrhea received a single dose of 400 mg of ofloxacin. Clinical and microbiologic cure was evident in 86 of 88 patients evaluated at seven days after treatment and in 71 of 72 patients at 14 days. Three patients developed postgonococcal urethritis; the cause was chlamydial in two. The patients with chlamydial infection received 200 mg of ofloxacin twice daily for seven days. Clinical and microbiologic cure was evident in all 78 patients evaluated one day after treatment and in 73 of 74 patients at 14 days. Side effects were reported by 11 patients. It is concluded that ofloxacin is a safe and effective treatment for uncomplicated gonorrhea in patients with and without concurrent chlamydial infections. PMID- 1933995 TI - Imipenem/cilastatin as secondary therapy for bacterial infections. AB - Imipenem/cilastatin (IPM/CS) was used to treat 39 documented infections in patients who had failed to respond to other antibiotic regimens. The overall response rating was 76.9%. Respiratory infections responded less frequently (efficacy rating, 55.6%) to IPM/CS than abdominal infections, urinary tract infections, or sepsis. Methicillin-resistant Staphylococcus aureus, Xanthomonas maltophilia, and Acinetobacter calcoaceticus were less sensitive to IPM/CS therapy than the other bacterial strains encountered. Respiratory tract infections were though to be less responsive to IPM/CS, probably because imipenem resistant strains of S aureus were present in most of those cases. It is concluded that IPM/CS is well tolerated and effective in the treatment of various bacterial infections. PMID- 1933996 TI - Treatment of posttraumatic osteitis with intravenous ofloxacin. AB - The subjects were 25 patients with osteomyelitis (n = 17) or other bone or joint infections, scheduled for surgical procedures, including debridement, sequestrectomy, and bone resection and reconstruction. Staphylococcus aureus was isolated in 22 patients, Staphylococcus epidermidis in one, Streptococcus haemolyticus in one, Pseudomonas aeruginosa in one, and a Pasteurella species in one. During surgery and for a mean of four days after surgery, each patient received 200 mg of ofloxacin intravenously twice daily (one patient received 300 mg and another received 400 mg twice daily). The patients were then given 200 mg of ofloxacin orally twice daily until the wound was healed (after a mean of 18 days). The wound was healed in all patients and no cases of reinfection occurred. It is concluded that intravenous ofloxacin given perioperatively may be more effective than oral ofloxacin in the management of osteomyelitis. PMID- 1933998 TI - Effects of dilevalol and propranolol on hemodynamics in patients with essential hypertension. AB - Eighteen patients with essential hypertension received 50 to 200 mg of dilevalol or 60 to 90 mg of propranolol daily for six weeks. Mean arterial blood pressure and venous pressure were significantly reduced in the dilevalol-treated patients at six weeks but were unchanged in the propranolol-treated patients. The cardiac index and systemic vascular resistance remained unchanged in the dilevalol group, but were significantly reduced (cardiac index) or increased (systemic vascular resistance) in the propranolol group. No changes in heart rate were noted in either treatment group. It is concluded that dilevalol has some ideal features for the treatment of hypertension, but further research is needed to determine the causes of fatal hepatotoxicity reported in a few cases. PMID- 1933997 TI - Ofloxacin in the treatment of lower respiratory tract infections: report of a prospective, comparative trial. AB - The subjects were 241 patients with lower respiratory tract infections treated at two medical centers in Austria; 161 of the patients were evaluated clinically and, of these, 69 were evaluated bacteriologically. The patients were randomly assigned to receive ofloxacin (n = 101) or a comparison drug (doxycycline [n = 27] or amoxicillin-clavulanate [n = 33]). The mean age of patients in the ofloxacin group was 61 years; that of patients in the comparison groups was 64 years. The mean duration of treatment was nine days; most patients received the study drug intravenously for three days and then orally for four to seven days. In most patients, the doses were 200 mg of ofloxacin twice daily; 100 mg of doxycycline twice daily; or 2,200 mg of amoxicillin-clavulanate intravenously two or three times daily, followed by 625 mg orally two to four times daily. The clinical response was rated satisfactory (all pretreatment symptoms disappeared) in 28% of the ofloxacin-treated patients and in 22% of the other two groups; improved (all except one symptom improved) in 70% and 65%, respectively; and unsatisfactory in 2% and 13%, respectively. The bacteriologic response was rated satisfactory in 59% of the 39 evaluable ofloxacin-treated patients and in 50% of the 30 patients in the other two groups. Most of the unsatisfactory responses were associated with persistent strains of Streptococcus pneumoniae. Transient side effects of mild to moderate severity were noted in nine of the 101 ofloxacin treated patients and in seven of the 60 patients in the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1933999 TI - Transdermal clonidine as an adjunct to sustained-release diltiazem in the treatment of mild-to-moderate hypertension. AB - An open-label study was conducted to evaluate the clinical safety and efficacy of transdermal clonidine as an adjunct to sustained-release (SR) diltiazem (90 mg twice daily) in mild-to-moderate hypertension. Ninety patients with a mean baseline sitting blood pressure of 154/102 mmHg were given 90 mg of diltiazem SR twice daily and transdermal placebo. After four weeks of therapy, 21 patients (23%) had trough sitting diastolic blood pressures (DBP) less than 90 mmHg and were withdrawn. Of the remaining 69 patients (DBP greater than or equal to 90 mmHg), 60 (mean blood pressure 149/98 mmHg) continued to receive 90 mg of diltiazem SR twice daily, to which was added transdermal clonidine, titrated as needed (3.5 cm2, 7.0 cm2, or 10.5 cm2) to achieve blood pressure control. During titration, 58 patients achieved DBP less than 90 mmHg, with a mean blood pressure of 133/84 mmHg. Of these patients, 54 completed an eight-week maintenance period, during which their mean blood pressure was 137/84 mmHg. No significant decrease in pulse or change from baseline in lipid profiles (high-density lipoprotein, low density lipoprotein, apolipoprotein A-I, apolipoprotein B) was observed with combination therapy. The most frequently reported side effect during maintenance therapy was mild skin irritation at the transdermal application site. One patient was withdrawn because of contact dermatitis. Compliance with the oral twice-daily regimen was variable, with 83% of patients failing to take diltiazem SR at the prescribed dosing intervals 80% to 100% of the time. Transdermal clonidine was worn as directed by 97% of patients. It is concluded that transdermal clonidine in combination with diltiazem SR is safe and effective in the treatment of mild to-moderate hypertension. PMID- 1934000 TI - Comparison of the pharmacokinetic profiles of two oral controlled-release morphine formulations in healthy young adults. AB - The pharmacokinetic profiles of two oral controlled-release morphine formulations, MS Contin tablets and Roxanol SR tablets, were compared to evaluate their bioequivalence. In a sequential, crossover study, 18 healthy young male volunteers received single 60-mg doses (two 30-mg tablets) of each formulation and provided 15 serial blood samples over 24 hours, which were assayed to determine their morphine concentrations by high-performance liquid chromatography. Analysis of variance revealed significant differences between the treatments for maximum plasma concentration (P less than 0.001), area under the plasma concentration curve from zero to 12 hours (P less than 0.01), and apparent elimination half-life (P less than 0.001). No significant differences were found for time required to reach maximum plasma concentration and area under the plasma concentration-time curve from zero to 24 hours. The results show that the two morphine preparations are not bioequivalent. PMID- 1934001 TI - Effect of health education in promoting prescription refill compliance among patients with hypertension. AB - A multifactorial health-education program designed to enhance compliance with a once-daily regimen of atenolol was evaluated among 453 patients enrolled in health maintenance organizations (HMOs). The initiation of the 180-day study period was used to classify patients as either new or existing cases of hypertension. In turn, patients in these two categories were randomly assigned to a control or an experimental group. Patients assigned to the experimental groups received an enrollment kit upon exercising their initial prescription (new patients) or their first refill request (existing patients). The kit contained: a 30-day supply of atenolol; an educational newsletter about hypertension; information on nutrition and life-style changes; and an explanation of the intent and content of the program. Before the next scheduled prescription-refill date, each patient was contacted by telephone to inquire about his or her experience with the therapy and to stress the importance of adherence to the regimen. Each month thereafter, the newsletter and an enclosed prescription-refill reminder were mailed to each patient. The medication possession ratio, defined as the number of days' supply of atenolol obtained by a patient during the 180-day study period, was significantly (P less than or equal to 0.001) enhanced for the new and existing experimental groups relative to the control groups. Multiple regression analyses revealed that enrollment in the health-education program increased the number of days' supply of atenolol obtained by existing patients by 27 (P less than or equal to 0.001), and by new patients by 40 (P less than or equal to 0.001). PMID- 1934002 TI - Nicardipine in the treatment of outpatients with cerebrovascular disorders. AB - A drug surveillance study was conducted, aimed at evaluating the efficacy and safety of nicardipine in outpatients with cerebrovascular diseases and at assessing the changes in nonfocal symptoms in the treated patients. The 3,150 outpatients (mean age, 68.9 years) were being treated by general practitioners and neurologists in Barcelona, Spain. Cerebral embolism was diagnosed in 4.0%, cerebral thrombosis in 13.0%, transitory ischemic attack in 28.0%, and chronic cerebral ischemia in 55.0%. The daily dose of nicardipine ranged from 20 to 180 mg; 87.7% of the patients received 60 mg of nicardipine daily. Concomitant medications were being taken by 89.1% of the patients. Treatment was evaluated in 2,913 patients. After 60 days of treatment, marked improvement was noted in 31.0% of the patients, moderate improvement in 39.0%, slight improvement in 20.0%, and no change in 10.0%. Marked or moderate improvement was noted in 69.6% of the patients who received nicardipine alone and in 66.9% of the patients who received concomitant medications. Clinically significant drops in blood pressure during treatment were found in the hypertensive patients. Side effects were reported by 14.5% of all patients and by 4.6% of the patients who received nicardipine alone. It is concluded that the daily administration of nicardipine is safe and effective in outpatients with cerebrovascular disorders. PMID- 1934004 TI - Milestones in clinical pharmacology. Psychopharmacology--depression and anxiety. PMID- 1934003 TI - Simvastatin versus pravastatin: efficacy and tolerability in patients with primary hypercholesterolemia. AB - One hundred patients with primary hypercholesterolemia (total plasma cholesterol greater than or equal to 6.2 mmol/L [240 mg/dl]) were enrolled in an open, randomized, parallel comparative study of simvastatin and pravastatin. All patients started or continued a standard lipid-lowering diet for at least six weeks prior to entry into the four-week placebo baseline period. Fifty patients received simvastatin and 50 patients received pravastatin, both at the recommended starting dose of 10 mg/day, for a treatment period of six weeks. Total cholesterol levels were reduced by 24% (from 7.59 mmol/L to 5.80 mmol/L) with simvastatin, and by 15% (from 7.48 mmol/L to 6.35 mmol/L) with pravastatin. Low-density-lipoprotein cholesterol levels were reduced by 33% and 22% and high density-lipoprotein cholesterol levels were increased by 10% and 7% with simvastatin and pravastatin, respectively. Plasma total triglyceride levels were reduced by 12% with simvastatin and by 6% with pravastatin. Adverse experiences were similar between treatment groups and both drugs were well tolerated. No patients were withdrawn from the study due to clinical adverse experiences; one patient in the pravastatin group required a reduction in dose to 5 mg/day due to insomnia. At the recommended starting dose, simvastatin had a significantly greater lipid-lowering effect than pravastatin. These results may have implications for the appropriate lipid-reduction therapy for patients at risk of coronary heart disease. PMID- 1934005 TI - Interferon-gamma C-terminal function: new working hypothesis. Heparan sulfate and heparin, new targets for IFN-gamma, protect, relax the cytokine and regulate its activity. AB - Structure and function of the interferon-gamma C-terminal extremity has been widely studied. A basic amino acid cluster located in this domain is involved in the tridimentional structure of the protein and is essential for the biological activity. This specific group of amino acid is also involved in the binding of interferon-gamma to basement membrane or cell surface heparan sulfate. Once bound to heparan sulfate, interferon-gamma is protected from proteolytic cleavage and it is suggested that the protein folds in a new relaxed conformation, with increased stability. PMID- 1934006 TI - Erythropoietin expressed in granular convoluted tubule cells of mice submandibular glands under hypoxia, anemia, and nephrectomy. AB - Immunohistochemically detectable erythropoietin-like substance(Epo) in granular convoluted tubule(GCT) cells of submandibular glands (SMG's) was examined in mice in which hemolytic anemia had been induced by phenylhydrazine (ph), and in mice subjected to hypoxia, nephrectomy, or testosterone (TP) injections. Staining for Epo was negative in GCT cells of SMG's in normal mice, while positive staining occurred in GCT cells of the anemic mice and mice subjected to hypoxia or nephrectomy. A positive Epo reaction was also revealed at the luminal borders of distal tubules, and in cells of proximal and distal tubules in the kidney, and in some hepatic and spleen cells, of mice that had received combination regimens producing anemia and hypoxia, or had been nephrectomized. Increased staining of Epo was found in GCT cells of SMG's, and in proximal and distal kidney tubules of mice given the combination treatment plus TP injections. The detection of Epo in GCT cells suggests these extrarenal cells to be sites of accumulation or biosynthesis of the protein under certain specific conditions such as hemolytic anemia and hypoxia. PMID- 1934007 TI - Cerium as amplifying agent--an improved cerium-perhydroxide-DAB-nickel (Ce/Ce H2O2-DAB-Ni) method for the visualization of cerium phosphate in resin sections. AB - A new visualization (Ce/Ce-H2O2-DAB-Ni) procedure for cerium (Ce III) phosphate in semithin and ultrathin plastic sections (Epon 812, Lowicryl K4M, glycol methacrylate) of rat kidney tissues that had been incubated before embedding for the demonstration of phosphatases (alkaline and acid phosphatase, 5(1) nucleotidase, Mg-dependent ATPase) is described. For this purpose the hydrophobic Epon resin was removed in NaOH-ethanol solution, whereas the hydrophilic Lowicryl and methacrylate sections did not required any etching. The primary reaction product Ce III-phosphate was amplified in a Ce III-citrate solution, subsequently oxidized with H2O2 and then visualized in a H2O2 containing DAB-nickel medium (Ce IV-perhydroxy induced DAB polymerization principle). The method yielded a very clear localization of enzyme activity. The final reaction product (DAB-nickel polymers) in 0.5 - 2.0 microns semithin sections is blue-black; the background staining is completely prevented. An increase of the staining contrast was obtained by posttreatment with OsO4 (osmium black formation). Furthermore, the enzyme reaction product could be demonstrated in 40 nm thick ultrathin sections by silver intensification, which utilized the high argyrophilia of the polymerized DAB-nickel complexes. This procedure replaces the earlier published technique. PMID- 1934008 TI - Electron microscopic radioautographic study on the incorporation of 3H-proline by mouse decidual cells. AB - A qualitative radioautographic analysis showed that mature decidual cells of the mouse are able to incorporate 3H-proline. After 1 hour silver grains are concentrated mainly over these cells although some of them can be found over collagen fibrils. After 2,6 and 24 hours there is a progressive increase of silver grains on the extracellular space most of them concentrated over thick collagen fibrils. These results strongly indicate that mature decidual cells of the mouse produce collagen and that they conserve a behavior of the fibroblast from which they originated. PMID- 1934009 TI - Cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase activity in the somatic cells of the seminiferous tubules. I. Isoform analysis. AB - In this work firstly are reported the chromatographic analysis of cAMP dependent protein kinases present in the cytosols obtained from rat Sertoli cells and peritubular cells. In both cell types two different isoenzymes have been detected, one eluting at 40-80 mM KC1 (type I) and a second one eluting at 150 200 mM KC1 (type II). Only the type I was strongly stimulated by cAMP whereas the type II was slightly cAMP dependent both in the Sertoli cells and in the peritubular cells. PMID- 1934010 TI - Cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase activity in the somatic cells of the seminiferous tubules. II. Effect of retinol. AB - The effect of retinol on cyclic AMP dependent protein kinase activity of Sertoli cells and peritubular cells isolated from prepubertal rats has been investigated. Treatments longer than six hours induced a significant inhibition of type I protein kinase activity of Sertoli cells without appreciable variation of type II protein kinase. Short time treatments with the vitamin did not affect the Sertoli cell protein kinase activity. The vitamin A addition did not induce any appreciable variation of peritubular cell protein kinase activity. PMID- 1934011 TI - Thermogravimetry study on the water in secretory tissues of rabbit. AB - Isothermic and dynamic thermogravimetry was applied to rabbit parotid and submandibular glands to quantitate and characterize the water present inside them. Isothermic thermogravimetry demonstrated that at 95 degrees C a quota of water is still present in the samples. Dynamic thermogravimetry evidenced that temperatures higher than 200 degrees C are required for the release of the highest energy bound water from both glands. In addition during present research it was found that submandibular gland, an organ considered histologically homogenenous, reveals an heterogeneous distribution of water. PMID- 1934012 TI - Cell separation system studied by mixed culture of single wild strain with tetrads-forming mutant strain of Micrococcus luteus. AB - Mixed culture study of singly occurring wild strain IFO 3333 of Micrococcus luteus and a tetrads-forming mutant strain MT, in the absence or presence of trypsin, supported our previous assumption that at least two kinds of separation systems were involved in cell separation of M. luteus, the one having a physiological role in cutting off the outermost layer of the cell wall (separation system-Om) and the other in cutting off the inner layer of the "proper" cell wall or the septum (separation system-In). The separation system-Om of IFO 3333 insensitive to trypsin substituted, freely from the cells, for that of MT sensitive to trypsin. PMID- 1934013 TI - Variation of transaminases and lactate dehydrogenase in irradiated Biomphalaria alexandrina snails. AB - Effect of ultraviolet and gamma radiations on the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LD) in Biomphalaria alexandrina snails, the specific intermediate host of schistosomiasis, was investigated. Changes in the electrophoretic pattern of LD in the species under study were also taken as a measured parameter and the effect of gamma-irradiation on the glutathione content in the haemolymph of the snails have been included. PMID- 1934014 TI - Transient accumulations of glycosaminoglycans in rat and chicken cerebellar cortex during development. AB - Modifications of glycosaminoglycans at neuropile of rat and chicken cerebellum during development were histochemically studied. The application of Alcian Blue staining techniques and enzymatic degradations permitted to reveal in both species that in earlier stages of cerebellar development hyaluronic acid is present throughout neuropile of entire cerebellum but it accumulated preferentially at the medullary region and around precursory Purkinje cells where it showed a mucoid-like appearance. This substance was related with cell migration and aligning processes. At the middle of cerebellar development, around 2nd postnatal week in rat and 12-16 embryonary days in chick, a new polyanionic transient accumulation, presumably chondroitinsulphate, became present at the medullary region following the longitudinal axis of folium and limiting the forming granular layer, being this substance mainly related with polarity processes by controlling or guiding the growing cones of afferent fibers, which enter massively to cerebellar cortex. It disappeared as myelination progressed. Also from the middle stage of development onward, beside glycosaminoglycans, other polyanionic substances were present at the molecular and granular layer neuropile and at the cytoplasm of some nerve cells. These macromolecules were rather related with nerve cell differentiation and maturation. PMID- 1934015 TI - Recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) induces human macrophage production of transforming growth factor-alpha. AB - Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is known as an inducer of proliferation and functional activation of myeloid cells. This study was carried out to characterize the effect of purified recombinant human GM-CSF (rhGM CSF) on induction of TGF-alpha in macrophages. Using Northern blot analysis and immunoassays, we show here that rhGM-CSF markedly stimulates production of TGF alpha messenger RNA and protein in normal tonsil macrophages. The findings are consistent with macrophages being a normal inducible source of TGF-alpha which may be an important mediator of various activities of GM-CSF both in hematopoietic and non-hematopoietic cells. PMID- 1934016 TI - A new enzymatic activity participating in the initiation of glycogen biosynthesis in rat brain. AB - A rat brain extract, able to synthesize from UDP-Glc an alpha-1,4-glucan covalently bound to a protein in the absence of added primer is described. The compound formed is precipitable by dilute trichloroacetic acid (TCA). In the presence of glycogen, added as primer, this molecule is enlarged and is not precipitable by TCA. Unprimed and primed activities differ in several aspects, such as the behavior in the presence of some effectors, and the optimum pH. Umprimed and primed activities presented two pHs optima, both sharing only one. The proteoglucans synthesized under the different pHs gave different patterns after analysis under denaturing PAGE and the oligosaccharides synthesized on the protein backbone differ in the glucosyl length. It is concluded that also in rat brain, the initiation process of glycogen biosynthesis is mediated through the formation of a glycoprotein. Our present results showed that the step of the putative "Glycogen Initiator" proposed by use before, requires two enzymes UDPGlc transglucosylating activities, Glycogen Initiator 1 and Glycogen Initiator 2, before Glycogen Synthase in the alpha-1,4-glucosidic linkages formation. PMID- 1934017 TI - Some molecular properties of human seminal transferrin (HSmT) in comparison with human serum transferrin (HSrT). AB - In this paper we report some structural features of human seminal transferrin (HSmT) in comparison with the homologous protein purified from human serum (HSrT). In particular, the sequence of the first 13 N-terminal amino acids of HSmT shows 12/13 of identity with the first 13 N-terminal amino acids of HSrT, the ninth residue of the former protein being not definitely determined. Moreover, HSrT and HSmT analysed under the same conditions, by means of reversed phase HPLC, thiol groups determination and second derivative spectroscopy, show a different content of amino acids. In particular, HSmT exhibits mainly: i) a lower Asx/Glx ratio; ii) a reduction of about 50% in Cys residues; iii) a decrease of Tyr and Trp residues. Eventually oligosaccharide parallel analyses of HSmT and HSrT show the same glycosidic bond and almost the same sugar content (around 5.5% w/w); conversely, HSmT lacks of sialic acid residues and probably it contains fucose. These results, taken all together, could be sound of interest to a better understanding of the possible physiological roles of HSmT. PMID- 1934018 TI - Rat lactase activity and mRNA expression in relation to the thyroid and corticoid status. AB - The effect of glucocorticoids and thyroid hormones on lactase expression was investigated along the small intestine of rats. In sucklings thyroxine injections promoted a precocious drop of enzyme activity but not of mRNA. Hydrocortisone did neither modify lactase activity nor its mRNA expression. In adults decreasing the amount of thyroid hormones led to a slight and reversible increase of the lactase mRNA content whereas lactase activity rised more dramatically. Thus, thyroid hormones in contrast to corticoids, are involved in the posttranscriptional control of lactase during the suckling period. Yet, none of these hormones might induced the modification of the longitudinal distribution of the lactase mRNA that occurred at weaning. PMID- 1934019 TI - Pulmonary surfactant obtained from starved rats enhances phagocytosis of alveolar macrophages. AB - Phagocytic activity of alveolar macrophages (AM) was enhanced by pulmonary surfactant obtained from bronchoalveolar lavage fluid of rats starved for 2 days, as compared to fed. The enhanced activity of phagocytosis was dependent on the dose of surfactant. The prepared surfactant showed a different protein to phospholipid ratio of 0.108 in fed and 0.234 in 2 days starved, because of an increased ratio of protein in surfactant from 2 days starved rats. F(ab')2 anti surfactant protein inhibited the enhanced AM phagocytosis by surfactant. These results suggested that the enhancement of AM phagocytosis in 2 days starved rats was on account of an increase of protein in their surfactant compared to fed. PMID- 1934020 TI - Further studies on the lethal and mutagenic effects of 8-methoxypsoralen-induced lesions on plasmid DNA. AB - Our previous results on the genotoxic effect of 8-methoxypsoralen-induced lesions on pBR322 suggested an important involvement of an inducible error-free repair pathway in the repair of plasmid lesions. We present herein further results obtained in order to explore that possibility, together with a more general report on the subject. pBR322 treated with increasing concentrations of 8-MOP plus fixed UVA light irradiation was used to transform several E. coli strains differing in their repair capacities, and plasmid survival and mutagenesis were determined. Survival results suggested that crosslinks were completely lethal in pBR322 whereas monoadducts were partially removed from plasmid DNA mainly through an error-free excision pathway. A mutagenic repair pathway did not show a significant contribution to the total repair process. Cell preirradiation stimulated plasmid recovery in recA+ strains, including the umuC strain, thus confirming our previous results indicating that an inducible error-free repair had occurred. Globally, our results showed a strong requirement on the excision pathway for the repair of psoralen-damaged plasmid DNA. In contrast, the recA dependent pathway was needed only for SOS induction. After a theoretical correction of the data for estimating the effect only due to 8-MOP adducts, a different pattern of repair mechanisms appeared to be involved. PMID- 1934021 TI - Correlation between secretion pattern and metastatic potential from drug-treated 3LL tumor cell line. AB - In the present study, we described the effects of three different drugs, A23187 calcium ionophore (A23187), indomethacin (IND) and phorbol myristate acetate (PMA), on the secretion pattern and the metastatic potential in the low metastatic 3LL tumor cell line. The results evidence that a low molecular weight protein fraction is always secreted in an higher amount in drug treated cells than in untreated cells independently of the drug used. In addition to their effects on secretion pattern, the three drugs assayed enhance noticeably the metastatic rate in vivo of the 3LL cells. The data confirm our earlier observations showing that our high performance gel permeation chromatography (HPGPC) method is suitable for discriminating even between cells with a different degree (low and high) of metastatic potential by its chromatographic secretion pattern and that alterations in the secretion pattern from treated cells are related with changes in the degree of metastatic potential of these cells. PMID- 1934022 TI - Enzyme histochemical expressions of smooth muscle cell modulation in arterial development, hypertension and remodeling. AB - In order to define metabolic profiles of smooth muscle cell (SMC) modulation, 16 enzyme activities linked to nucleotide hydrolysis, lipolysis, lysosomal reactivity and intermediate glucose catabolism were compared in four rat arterial models, exhibiting four metabolic phenotypes of modulated smooth muscle cells: (i) "primary synthetic" statein immature aorta; (ii) "contractile" state in adult aorta; (iii) "hypertensive" state in aorta of hypertensive rat, SHR; (iiii) "secondary synthetic" state in diffuse intimal thickening of ligated carotid artery. Contractile SMC presented strong activities of enzymes linked to nucleotide ester hydrolysis and contractility (ATP-A-Ca, ATP-A-Mg, ATP-A-Ca/Mg, 5'nucleotidase) and to lipolytic process (butyryl cholinesterase, acid esterase). These enzyme activities were more pronounced in "hypertensive SMC". Incontrast, the same enzymes were weakly active or not expressed in "synthetic SMC". Increased lysosomal enzyme reactivity was a particular expression of "secondary synthetic SMC". The observed enzyme abnormalities in reactively modulated SMC (proliferative-synthetic phenotype) might be related to the loss of contractility and to the enhanced cell proliferation and lipid accumulation, characteristic features of modulated SMC in atherogenesis. PMID- 1934023 TI - Rheumatoid arthritis modifies basal and insulin-mediated glucose uptake by human synoviocytes. AB - Basal and insulin-mediated glucose uptake were studied in human synovial cells. Cell cultures were established from samples of synovium obtained at synovectomy from patients with osteoarthritis (non-rheumatoid synovial cells, NRSC) or rheumatoid arthritis (rheumatoid synovial cells, RSC). Basal glucose uptake was significantly higher in RSC than in NRSC. NRSC were sensitive to insulin at near physiological concentrations (10(-8)M), with maximal transport occurring after a 30-min. association time (27.2 +/- 2.0%, mean +/- SEM). Insulin did not stimulate significantly 2-deoxy-D-glucose uptake in RSC, regardless of the association time (up to 120 min.) or the insulin concentration (10(-10) to 10(-6) M). Treatment of NRSC with human recombinant interleukin-1 beta (IL-1 beta) enhanced glucose uptake to a level similar to basal uptake by RSC. These results suggest that autocrine production of IL-1 beta by RSC could be responsible for the higher basal glucose uptake by these cells. PMID- 1934024 TI - Beta-D-xyloside induced modulations of glycosaminoglycans, proliferation, and cytoskeletal organization of rat liver myofibroblast-like cells (transformed fat storing cells). AB - Transformed fat storing cells, i.e. myofibroblast-like cells are the major source of proteoglycans in injured liver. In the present study p-nitrophenyl-beta-D xylopyranoside (PNP-Xyl), a specific metabolic inhibitor of proteoglycan synthesis, was used to analyze some details of altered glycosaminoglycan metabolism, proliferation, morphology and cytoskeletal organization of myofibroblast-like cells (secondary cultures of fat storing cells) under conditions of abrogated proteoglycan synthesis. PNP-Xyl increased dose dependently the synthesis of [35S] sulfate-labelled medium glycosaminoglycans, among which chondroitin sulfate formation was stimulated predominantly. The distribution and composition of glycosaminoglycans in the cellular and cell surface compartments were affected differently. Production of medium hyaluronan was reduced by more than 40% at 5 mM PNP-Xyl. The compound inhibited dose dependently the mitotic activity of myofibroblast-like cells without affecting viability. The morphologic appearance was changed at 5 mM PNP-Xyl and the organization and expression of desmin and smooth muscle iso-alpha-actin, both important markers of myofibroblast-like cells, were also modified by PNP-Xyl. Inhibition of proliferation, morphologic changes, and cytoskeletal disorganization were fully and rapidly reversible upon removal of the drug. The results support the notion of a direct or indirect role of proteoglycans in maintaining important functions of myofibroblast-like cells in culture. PMID- 1934025 TI - Inhibin-like and gonadotropin-like immunoreactivity in pituitary cells of male monkeys (Macaca fascicularis, Macaca mulatta). AB - Inhibin-like immunoreactivity was detected by immunocytochemistry in the pituitaries of untreated male crab-eating macaques (cynomolgus monkey) and rhesus monkeys, in rhesus monkeys actively immunized against FSH, and in one orchidectomized crab-eating macaque. Localizations were performed by the immunogold-silver staining with 5-nm colloidal gold-conjugated second or third antibodies and by the alkaline phosphatase-anti-alkaline-phosphatase technique. Two different inhibin-specific antisera, raised against the alpha-subunit or the entire inhibin molecule, provided identical staining patterns. Positive label was confined to the pars distalis of the pituitary and occurred exclusively in the cytoplasm of morphologically different cell types throughout the pars distalis in all pituitaries. Staining was most prominent in clusters of chromophobic cells. The presence of inhibin-like activity in the pituitary of an orchidectomized monkey with undetectable serum inhibin levels suggests that inhibin is produced within the pituitary gland. Co-localization studies for the beta-subunits of the gonadotropic hormones revealed that on average 82% of the gonadotropes were bihormonal. Using the same protocol, co-localization of inhibin-like activity with gonadotropin-like immunoreactivity revealed only a small degree of common distribution (less than 15%). Inhibin-positive cells were frequently in close proximity to gonadotropic cells and, thus, paracrine effects of inhibin on gonadotropin-synthesizing cells are conceivable. PMID- 1934026 TI - Immunoreactivities for epidermal growth factor (EGF) and for EGF receptors in rats with gastric ulcers. AB - The present study was aimed at assessing whether epidermal growth factor (EGF) and its receptors are present in the gastric mucosa during the healing of gastric ulcers. Immunohistochemical, immunochemical and functional studies were performed in rats after induction of ulcers in the oxyntic mucosa. Controls, which included non-operated and sham-operated animals, displayed only rare cells in the bottom of the oxyntic glands showing EGF-like immunoreactivity. Within one day after ulcer induction, a markedly increased number of chief cells in undamaged mucosa showed intense staining. Concomitantly, there was an increased immunoreactivity for EGF receptors in the mucous neck cells. Maximal immunostaining for both compounds was observed at 3 days after ulcer induction; augmented staining was still demonstrable after 3 weeks. RIA revealed significantly increased EGF concentration in the oxyntic mucosa three days after ulcer induction, and at this stage stimulated gastric acid secretion, measured in a parallel group of chronic fistula rats, indicated significant inhibition. The transient increases in EGF like and EGF receptor immunoreactivities may stimulate gland cell proliferation. The local release of EGF-like substances may also serve to reduce gastric acidity and thereby promote ulcer healing. PMID- 1934027 TI - Localization of neuropeptide Y-immunoreactive cells and fibres in the brain of the Japanese quail. AB - In the present study, we have demonstrated, by means of the biotin-avidin method, the widespread distribution of neuropeptide Y (NPY)-immunoreactive structures throughout the whole brain of the Japanese quail (Coturnix coturnix japonica). The prosencephalic region contained the highest concentration of both NPY containing fibres and perikarya. Immunoreactive fibres were observed throughout, particularly within the paraolfactory lobe, the lateral septum, the nucleus taeniae, the preoptic area, the periventricular hypothalamic regions, the tuberal complex, and the ventrolateral thalamus. NPY-immunoreactive cells were represented by: a) small scattered perikarya in the telencephalic portion (i.e. archistriatal, neostriatal and hyperstriatal regions, hippocampus, piriform cortex); b) medium-sized cell bodies located around the nucleus rotundus, ventrolateral, and lateral anterior thalamic nuclei; c) small clustered cells within the periventricular and medial preoptic nuclei. The brainstem showed a less diffuse innervation, although a dense network of immunopositive fibres was observed within the optic tectum, the periaqueductal region, and the Edinger Westphal, linearis caudalis and raphes nuclei. Two populations of large NPY containing perikarya were detected: one located in the isthmic region, the other at the boundaries of the pons with the medulla. The wide distribution of NPY immunoreactive structures within regions that have been demonstrated to play a role in the control of vegetative, endocrine and sensory activities suggests that, in birds, this neuropeptide is involved in the regulation of several aspects of cerebral functions. PMID- 1934028 TI - Age-related accumulation of lysosomes and other cytological features in active thyroid follicles of the CBA mouse. AB - This study attempts to elucidate the mechanism through which lysosomal accumulation occurs with age in the epithelial cells of the thyroid gland and especially in the "active" follicles of the aging mouse thyroid. Thyroid morphology and function in old CBA (at least 24 months of age) male mice were compared with those in young (2 months of age) animals. The effects of different intake of iodine were tested and compared in both cohorts, each of which was divided into three groups: (i) low iodine group, (ii) moderate iodine group, and (iii) high iodine group. As expected, the present work confirmed the well-known accumulation with age of "cold" follicles coexisting with "active" follicles in the old mouse thyroid. Attention has been focused on the active follicles whose follicular cells contained in their cytoplasm a large number of pleomorphic dense bodies. The lysosomal nature of these bodies, referred to as secondary lysosomes, was confirmed by histochemistry; however, they displayed variability in acid phosphatase staining. In old animals, regardless of the type of iodine regimen, the ratio between relative follicular volume and relative colloid volume as determined by morphometry remained unchanged. Ultrastructurally, the relative volume occupied by secondary lysosomes in "active" follicles was always higher than in the young groups. Autoradiographic studies with 125I revealed that a large part of the radioactivity was located in secondary lysosomes of thyroid cells in "active" follicles of old mice when radioiodine was injected 3 weeks before death. Two different types of vacuoles were present in a non-negligible number of thyrocytes of the "active" follicles in aged cohorts. The first type was made up of grossly dilated rough endoplasmic cisternae, the second corresponded to intracytoplasmic microfollicular vacuoles. Both aspects have been described in conditions of chronic stimulation. It is concluded (1) that different intake of iodine for 6 weeks does not modulate the thyroid morphology in old mice; (2) that in the thyrocytes of the "active" follicles in old mice accumulation of secondary lysosomes occurs due to a slowdown of turnover; and (3) that the follicular cells of "active" follicles feature morphological aspects suggesting a hyperactive state compensating the lack of hormone production in the "cold" follicles. PMID- 1934029 TI - Differences in the immunoreactivity to phenylethanolamine-N-methyltransferase in the central adrenergic neurons of four strains of rats. AB - Immunocytochemistry was used to compare the immunoreactivity of adrenergic neurons to a well characterized specific immunoserum to phenylethanolamine-N methyltransferase (PNMT) in different strains of rats commonly used in research studies. In adult animals, marked differences were found in the PNMT immunoreactivity of neurons between Wistar rats and other strains, resulting in a lower PNMT-immunostaining intensity (i) within neuronal perikarya of the medulla oblongata, and (ii) more strikingly, within nerve fibers and terminals located in various brain regions. This low PNMT-immunoreactivity of nerve fibers was detected both in 14- and 35-day-old Wistar rats. On the other hand, the HPLC measurement of catecholamines, in particular of adrenaline in the hypothalamus and the medulla oblongata, did not show any difference between adult Wistar and Sprague-Dawley rats. These data suggest that the low PNMT-immunoreactivity observed in central adrenergic neurons of the Wistar rats is related to the poor recognition of the antigen by the PNMT-antibody used. Possibly, these nerve cells mainly display an isoform of the enzyme that is immunologically different from the PNMT contained within the adrenergic neurons of other rat strains. PMID- 1934030 TI - An electron-microscope and freeze-fracture study of the egg cortex of Brachydanio rerio. AB - We have examined the cortex of the teleost (Brachydanio rerio) egg before and during exocytosis of cortical granules by scanning, transmission, and freeze fracture electron microscopy. In the unactivated egg, the P-face of the plasma membrane exhibits a random distribution of intramembranous particles, showing a density of 959/micron2 and an average diameter of 8 nm. Particles over P- and E faces of the membranes of cortical granules are substantially larger and display a significantly lower density. An anastomosing cortical endoplasmic reticulum forms close associations with both the plasma membrane of the egg and the membranes of cortical granules. Exocytosis begins with cortical granules pushing up beneath the plasma membrane to form dome-shaped swellings, coupled with an apparent clearing of particles from the site of contact between the apposed membranes. A depression in the particle-free plasma membrane appears to mark sites of fusion and pore formation between cortical granules and plasma membranes. Profiles of exocytotic vesicles undergo a predictable sequence of morphological change, but maintain their identity in the egg surface during this transformation. Coated vesicles form at sites of cortical granule breakdown. Differences in particle density between cortical granules and egg plasma membranes persist during transformation of the exocytotic profiles. This suggests that constituents of the 2 membrane domains remain segregated and do not intermix rapidly, lending support to the view that the process of membrane retrieval is selective (i.e., cortical granule membrane is removed). PMID- 1934031 TI - Mast cells in rat dermis and jejunal lamina propria show a five-fold difference in unit granule volume. AB - The cytoplasmic granules of mast cells have a periodic multimodal size distribution in which the volumes of individual granules are integral multiples of the intermodal distance, a volume defined as the "unit granule" or v1. In this study, we used two 3-month-old male rats to analyze two classical mast cell subpopulations, dermal "connective tissue-type mast cells" and jejunal lamina propria "mucosal mast cells", for the morphometric characteristics of their cytoplasmic granules. Both v1 and the mean volume of individual cytoplasmic granules were much smaller in dermal than in jejunal mast cells (ratios of 1:5.5 and 1:4.2, respectively), but dermal mast cells contained 150% more granules per cell than did jejunal mast cells. The two types of mast cells did not differ significantly in total cell volume, nucleus volume, aggregate volume of cytoplasmic granules per cell or numbers of unit granules comprising a granule of mean volume. These findings add unit granule volume to the list of phenotypic characteristics which express significant variation in anatomically distinct populations of mast cells. PMID- 1934032 TI - Domains of neuronal heparan sulphate proteoglycans involved in neurite growth on laminin. AB - A single neuronal cell assay of neurite growth was utilized to determine types and domains of neuronal proteoglycans involved in neurite growth on laminin. Perturbations of biosynthesis and processing, enzymatic digestion with specific lyases, and competition with glycosaminoglycan side chains produced complementary data consistent with a molecular model implicating glycosaminoglycan (GAG) residues of heparan sulphate proteoglycans (HSPGs) in neurite growth. The observations suggest that HSPGs promote neurite growth on laminin by bridging between binding domains for HSPGs on laminin and on the neuronal cell surface, and that the bridge is tethered at both ends by non-covalent interactions between the binding domains and GAG side chains. Sulphation of the GAGs of HSPGs appears to be critical to the tethering and/or neurite growth-promoting activity of neuronal HSPGs. PMID- 1934033 TI - Properties of heart fibroblasts of adult rats in culture. AB - In the heart of the adult rat, fibroblasts are mainly responsible for the synthesis and deposition of the collagenous matrix. Because these cells in vitro may serve as an important model system for studies of collagen metabolism in heart tissue, we have cultured and characterized rat-heart fibroblasts from young adult and old animals. Conditions included use of media of different compositions with and without addition of ascorbate. Cells used were either cultured directly from fresh tissues or thawed previously frozen cells. Cultured cells were studied with respect to growth properties, morphology and ultrastructure and patterns of collagen. Heart fibroblasts generally resembled fibroblasts cultured from other tissues, but were more like skeletal muscle fibroblasts in that they deposited, in addition to type I collagen, type IV collagen and laminin. The fibroblasts showed a typical appearance in phase-contrast microscopy and electron microscopy. In the case of cells grown with added ascorbate, aligned collagen fibrils in the extracellular matrix showed a periodicity typical of type I collagen. The deposition of type I collagen occurred only in medium supplemented with ascorbate, and in that circumstance increased as a function of time past confluence; this was independent of the age of the animal from which the cells were obtained or of other changes of medium composition studied. Immunofluorescence studies with specific antibodies revealed that the cells deposited types I and IV collagens, laminin and fibronectin. In contrast to the case of type I collagen, the deposition of type IV collagen occurred in cells grown either with or without ascorbate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934034 TI - NADPH-diaphorase reactivity in adult and developing cat retinae. AB - We have examined the distribution and size of nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase reactivity in adult and developing cat retinae. From late gestation E (embryonic day) 58 to adulthood, NADPH-diaphorase reactivity was detected in amacrine cells with somata located in the inner nuclear layer (INL) and ganglion cell layer (GCL) and in processes spreading in the middle strata of the inner plexiform layer (IPL). Reactivity was also present in small rounded profiles located in the outer plexiform layer (OPL) and thought to be cone pedicles. The number of NADPH-diaphorase reactive cells present in adult retinae was about 40,000, 75% of these somata were located in the GCL, the remainder in the INL. At birth, however, there was more than double this number of labelled somata (85,000), the total gradually declining to reach adult values by P (postnatal day) 25. This loss of NADPH-diaphorase reactive somata may be partly explained by natural cell death (apoptosis) or by loss of the active diaphorase from the cells. The density distributions of NADPH-diaphorase reactive cells in the INL and GCL of retinal wholemounts reached maxima in regions slightly inferior to the area centralis at all ages studied. The principal topographical difference between adult and developing retinae was that the density gradient of NADPH-diaphorase reactive cells was steeper in adults than at younger ages. During early development, the somal and dendritic field diameters of NADPH diaphorase reactive cells at the area centralis were about the same size as those in the periphery; by adulthood, cells in the periphery were larger. The change in the somal diameter gradient apparently emerged because of a reduction in somal size of the centrally located cells. The change in the dendritic diameter gradient emerged because of a greater growth of peripheral cells as compared to central cells. We suggest that NADPH-diaphorase may have a role in the formation of synapses in the developing IPL. PMID- 1934035 TI - Current bibliography of cell calcium prepared by the University of Sheffield Biomedical Information Service. PMID- 1934036 TI - Characterization of Ca2+ transients induced by intracellular photorelease of InsP3 in mouse ovarian oocytes. AB - Ca2+ transients (measured with Fluo-3) were induced in single mouse ovarian oocytes by photolytic liberation of InsP3. The time course of cytosolic Ca2+ changes induced in this way is composed of distinct phases: upstroke, fast decline, slow declining plateau and fast decline to rest level. All the phases reflect mainly intracellular redistributions of the ion and not influx, since they are not strongly dependent on external Ca2+ or on changes in transmembrane potential. Often sustained Ca2+ oscillations followed the first InsP3-induced Ca2+ transient. These persisted for several minutes in the absence of external Ca2+. The initial rate of Ca2+ rise and the delay between the InsP3 stimulus and Ca2+ upstroke are correlated with the amount of liberated InsP3. A second InsP3 stimulation, applied during the plateau, causes only small Ca2+ elevations, lacking the upstroke phase. A second, full sized, transient could be elicited only after a complete return to the basal level. Vanadate, applied intracellularly, appeared to inhibit the re-uptake phase into the stores, stabilizing the plateau level. The present observations suggest that in mouse oocytes the InsP3-sensitive stores provide only a small and graded Ca2+ release which may then act as a trigger for a more substantial Ca(2+)-induced Ca2+ release (CICR) process. PMID- 1934037 TI - Calcium export by sodium-calcium exchange in bovine chromaffin cells. AB - Calcium efflux from bovine chromaffin cells in tissue culture has been examined after loading them with small amounts of Ca2+ by brief depolarization in media containing 20 mumol/l to 1 mmol/l Ca2+ and 45Ca2+ in trace amounts. In the presence of normal external Na+ and Ca2+ concentrations cells depolarized in media containing up to 200 mumol/l Ca2+ exported nearly 100% of their accumulated Ca2+ loads within 10 min and 20% within the first 5 s. In the absence of external Na+ and Ca2+ the proportion of a small (i.e., depolarization in 20 mumol/l calcium) Ca2+ load exported at any time point in the range to 10 min was approximately two thirds of the total efflux measured in their presence indicating that under these conditions the external Na+/Ca(2+)-dependent and Na+/Ca(2+)-independent mechanisms both contribute significantly to the export of calcium. At higher cellular loads of calcium (i.e., depolarization in 200 mumol/l to 1 mmol/l calcium) the Na+/Ca(2+)-dependent mechanism exported a progressively greater proportion of the accumulated Ca2+. Both sodium and calcium alone promoted a component of Ca2+ efflux; Ca2+ (i.e. calcium-calcium exchange) was as effective as Na+ (i.e. sodium-calcium exchange). The Km for Na+ stimulation of Ca(2+)-efflux (KNa) was approximately 65 mM. Increased external Mg2+ (from 1.2 to 10 mmol/l) increased the apparent KNa to 90 mM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934038 TI - Digitonin-aided loading of Fluo-3 into embryogenic plant cells. AB - This paper describes a method to load embryogenic plant cells with Fluo-3 in its cell impermeant form with the aid of digitonin. Attempts to load cells with Fluo 3/AM were all unsuccessful. Presumably the indicator is cleaved outside the cells and cannot penetrate in its acidic form. At a low pH, Fluo-3 enters the plant cells but normal Ca2+ homeostasis seems to be disturbed. Successful loading of Fluo-3 was achieved by adding 0.1% digitonin during incubation with the Ca(2+) indicator. A bright fluorescence was observed in the epidermal layer of heart and torpedo shaped somatic embryos of carrot with confocal scanning laser microscopy. Vacuoles were always without fluorescence which indicates that the dye, after loading, remains in the cytosol and does not leak out. The fluorescence intensity was sensitive to treatments with A23187 and EGTA. We conclude that Fluo-3 can be effectively loaded, with the aid of digitonin, into plant embryogenic cells in liquid culture. Therefore, we expect this technique to be very useful for the study of changes in cytosolic free Ca2+ levels during plant growth and development. PMID- 1934039 TI - [Study of exercise and serum lipids in puberty]. AB - For determining the relationship between serum lipids and exercise, an investigation was carried out, 275 students (mean age, 16.33 years) acted as an exercise group from Anhui province physical training school and Hefei physical training middle school exercise classes, and 309 students (mean age, 16.96 years) as a control group from Hefei normal school and Hefei physical training middle school general classes. The variables were studied which included age, height, body weight, Quetlete index, energy expenditure, TC, TG, and HDL-C. The survey shows that exercise may lower serum TG, increase TC and HDL-C levels. Energy expenditure, age, and height were identified as the most important predictors by the multiple linear regression analyses. These findings suggest that exercise may play significant role in primary prevention of the cardiovascular diseases. PMID- 1934040 TI - [A case-control study on risk factors of female hypertension in Tianjin City]. AB - A pair matched case-control study was conducted in 301 pairs female patients with essential hypertension and their controls. The data was analysed by the multiple conditional Logistic regression. The results showed the risk factors associated with hypertension were: body weight (OR = 1.17, 95% CI: 1.12-1.23), the family history of hypertension (OR = 2.18, 95% CI: 1.49-3.21) the family income (OR = 0.73, 95% CI: 0.56-0.94), heart rate (OR = 2.30, 95% CI: 1.41-3.76). OR for the age of menarche was significantly different before and after being adjusted by body weight. There were no relationship between the age of menopause, the age of the first birth, parties, oral contraceptive use or smoking status and hypertension. The paper suggested that the difference of prevalence of hypertension in male and female over 45 years old cannot be explained by menopause or the factors on birth in women. PMID- 1934041 TI - [Dietary factors and esophageal cancer: a case-control study]. AB - A hospital-based case-control study of 112 patients with esophageal cancer was conducted to explore the association of dietary factors with cancer of the esophagus. Each case was matched to one non-cancerous patient from surgical department in the hospital of the same sex, age (+/- 5 years), occupation (farmer or nonfarmer), and residence as control. Multivariate conditional logistic regression analysis showed that the consumption of moldy grains (odds ratio (OR), 4.08), pickled vegetables (OR, 2.57), tea drinking habit (OR, 5.65), and hot food consumption (OR, 2.53) were significant risk factors for esophageal cancer. Intake of eggs (OR, 0.30) and higher proportion of flour and rice in the grain ration (greater than 30% vs. less than or equal to 30%) (OR, 0.43) were protective factors. Relations between factors were also discussed in the paper. PMID- 1934042 TI - [An analysis of incidence mortality and survival rates of lung cancer in Beijing]. AB - In the past 30 years the lung cancer incidence rate in the countries all over the world has been on increase. A population-based cancer registry has been set up since 1976 in Beijing. The epidemiological features of lung cancer in Beijing during 1977-1986 were analysed. The data collected show that the lung cancer incidence and mortality ranked first among cancers at all sites and had been on increase from year to year. The annual average crude incidence rate of cancer was 31.3/100000 in male during 1982-1984, the world standard rate was 33.0/100000. Incidence due to lung cancer accounted for 20.3% of all male cancer cases. The crude incidence rate was 22.8/100000. Incidence due to lung cancer accounted for 16.1% among all female cancer cases. The sex ratio of the world standard incidence rates was 1.56. The lung cancer is one of the lesser prevised cancer and the five year relative survival rate is 6.5% for both sexes in 1982-1983. The lung cancer mortality rate in Beijing urban area is compared with other countries in the world, and it is found that the female mortality rate of lung cancer in Beijing is the highest. PMID- 1934043 TI - [Studies on the influencing factors of the infertility rate in the rural area of Jiangsu Province]. AB - This paper analyzed the influencing factors of the infertility rate in the rural area of Jiangsu province by means of chi 2 test and multiple regression model. The overall infertility rate was 5%. The results showed that the infertility rate was higher in older women, smokers, couples in the lower socioeconomic groups, much early or later married women. It is worth mentioning that the effect of variables affecting the fertility rate was difference between Southern Jiangsu area and Northern area. Women's habits of smoking and education level have a greater effect on the infertility rate in Southern Jiangsu area, whereas economic condition and women's marriage play a more prominent role in the North. PMID- 1934044 TI - [A case-control study of dangerous factors related to infertility]. AB - This paper reports the case-control study of dangerous factors related to infertility in Henan province during 1987-1988. There were two groups. One was a primary infertility group with 319 couples. The other was a normal fertility group with 714 couples, who were neighbours of the first group, among whom the women's age range was within 6 years old. The survey materials were analyzed by SAS programmes in the computer. The methods of analysis were single factor and logistic regression analysis of factors. The results of single factor analysis showed that in male, infertility had a close relationship with eating edible rude cotton seed oil; suffering from Varicocele; hydrocele of tunica vaginalis; sex dysplasia; breast dysplasia; puberty enuresis; parotitis after puberty; familial infertility and working under high temperature conditions. In female, menstrual disorder; a sexuality or pain during coitus; familial infertility; TB and other chronic diseases might be major contributors to the incidence of infertility. The results of logistic regression analysis of the factors related to infertility suggested that in male, eating edible rude cotton seed oil, suffering form varicocele; sex dysplasia; puberty enuresis; and in female, menstrual disorder; TB; consanguineous marriage, lower rate of coitus, frequent contact with pernicious substances might be major dangerous factors causing infertility. The results of the logistic regression analysis were different from those of the single factor analysis because the former not only analyzed the major influence of each factor but also considered the comprehensive effects of the relevant factors. PMID- 1934045 TI - [Observation on prevention of hepatitis B virus transmission between newly married couples by HBsAg vaccine]. AB - Sixty-one young men and women, whose finances were found to be HBsAg (+) or partly HBeAg (+), had undergone medical examination before marriage. They were divided into two groups and given HBV vaccine or placebo before marriage. Six months later, the seroconversion rates of anti-HBs in these two groups were 93.33% (28/30) and 6.45% (2/31), respectively. The difference was statistically significant (P less than 0.01). Six-twelve months after marriage, the HBsAg positive rates were 6.67% (2/30) and 61.29% (9/31), respectively. This difference was highly significant (P less than 0.001). The protective rate of HB vaccine reached 89.12%. The results suggested that it is important to vaccinate the susceptible persons to be married to enhance their immunity against HBV, especially when the finances were found to be HBsAg positive (+) before marriage. PMID- 1934046 TI - [The serogroup and serotype distribution of Leptospira in Sichuan Province from 1958-1987]. AB - This paper summarized the serogroup and serotype distribution of 7,560 strains Leptospira in Sichuan province from 1958 to 1987. At present, Leptospira 16 serogroup and 35 serotype have been found. The Icterohaemorrhagiae group Lai type is the major and stable serogroup and serotype in patients. We have proved that Rodents insectivores and domestic animals are the main reservoir host. The former carries Icterohaemorrhagiae group and the latter carries Pomona group. The serotype carried on the reservoir animal Apodemus agrarius is mostly Icterohaemorrhagiae Lai and is the principal infection source of Leptospirosis in Sichuan province. In addition, this paper discussed the reason of main serogroup change, the possible role of frog as an infection source of Hebdomadis Leptospirosis. PMID- 1934047 TI - [Quality evaluation of the immunoenzymatic reagent for detection of antibody to HIV]. AB - Comparing with foreign ELISA reagent and Western blot, evaluation of the quality of the immunoenzymatic reagent was done by testing four set of sera from residents in the border of Yunnan province and other provinces results suggested that the sensitivity of IE was 100% and its specificity was 99.4%. Other indexes were similar to imported ELISA reagent. So IE reagent can be used in national HIV surveillance. The quality evaluation is credible because of the great number of tested sera. PMID- 1934048 TI - [Uses of computers in epidemiology]. PMID- 1934049 TI - [Epidemiological characteristics and risk factors of cervix cancers in China]. PMID- 1934050 TI - Identifying people in need of rehabilitation in rural Zimbabwe. AB - The Ministry of Health of Zimbabwe has initiated eight Community-based Rehabilitation projects in rural areas. Within each project, a survey was undertaken to identify people with a disability who could benefit from these projects. This article discusses the set-up, outcome and shortcomings of the surveys. The results of the surveys are compared with previous studies on people in need of rehabilitation in Zimbabwe. The surveys led to three major findings: 1. The majority of the people in need of rehabilitation in the rural areas have not been in contact with rehabilitation services before; 2. The results of the surveys differ from previous studies in terms of the numbers of clients in the different diagnostic categories; 3. Community-based rehabilitation deals with a different group of clients compared with hospital-based Rehabilitation. The use of the ICIDH is recommended to standardise future surveys. Implications for the development of rehabilitation services are discussed in the article. PMID- 1934051 TI - The forgotten: the Zimbabwean elderly in hospital. PMID- 1934052 TI - Renal ectopia in Nairobi. AB - Forty-six patients with renal ectopia were investigated over a 5 1/4 years period. The male to female ratio was 15:31. Their ages ranged from 3 1/2 to 50 years. The commonest presentation was abdominal mass. The right kidney was involved in 50pc, the left in 28pc and both kidneys in 22pc of cases. Malrotation, hydronephrosis and fusion were the most frequent anomalies associated with the ectopia. One patient developed neoplastic change. PMID- 1934053 TI - The effect of prolonged exposure of rats to sub-lethal dose of acetaminophen. AB - In this report, we studied the effect of sub-lethal doses (20mg, 30mg, 100mg, 200mg and 300mg/Kg body weight) and duration of acetaminophen given intraperitoneally (i.p) to male albino rats; on the level of pc methaemoglobin and some liver function tests: Alkaline phosphatase, free and conjugated bilirubin. The study showed that the increase in pc methaemoglobin, free and conjugated bilirubin in rats treated with acetaminophen are significantly (P less than 0.05) greater than those for the control rats and that the measured parameters increase with acetaminophen concentrations. The results also show that the free bilirubin is probably displaced from plasma albumin. PMID- 1934054 TI - Quadriplegia prolonged unconsciousness and transient blindness after eclampsia- case report. AB - In eclampsia neurological complications carry a high maternal mortality and morbidity. The case of an unbooked 15-year-old primiparous teenager who presented in shock, unconscious, quadriplegic and transiently blind one day after home delivery is reported. Co-operative inter-departmental management was undertaken and the patient was discharged, satisfactorily recovered. PMID- 1934055 TI - Multiple targets for brefeldin A. PMID- 1934056 TI - A myb gene required for leaf trichome differentiation in Arabidopsis is expressed in stipules. AB - The GL1 gene is required for the initiation of differentiation of hair cells (trichomes) on the crucifer, Arabidopsis thaliana. This gene has been localized to a 4.5 kb DNA fragment by molecular complementation of gl1 mutants. DNA sequence analysis has shown that the protein encoded by GL1 contains a Myb DNA binding motif. Southern analysis and subsequence analysis of isolated lambda clones has established that GL1 is a member of an extensive myb gene family in Arabidopsis. The putative GL1 promoter directs the expression of the GUS reporter gene in non-trichome-bearing structures that appear to be stipules. This pattern of expression suggests that GL1 may control the synthesis of a diffusible signal that activates the developmental pathway for trichome differentiation. PMID- 1934057 TI - Microsurgical removal of centrosomes blocks cell reproduction and centriole generation in BSC-1 cells. AB - We have removed the centrosome from cultured BSC-1 cells by microsurgery, leaving enough cytoplasm with the nucleated cell fragment (karyoplast) to ensure survival and growth. In each experiment, we followed the fate of the karyoplast as well as the anucleate cell fragment (cytoplast) containing the original pair of centrioles. Experimental karyoplasts reestablish a juxtanuclear microtubule organizing center, an astral array of microtubules, and a compact Golgi apparatus. They enter and presumably complete S phase, and they grow beyond the size of an average BSC-1 cell. However, they do not regenerate centrioles in time periods equivalent to more than 10 cell cycles and do not undergo cell division. Control-operated cells with centrosomes left in the karyoplast progress through the cell cycle, duplicate the centrosome, and form clonal cell colonies. We conclude that the removal of centrioles uncouples cell growth from cell reproduction and impedes centriole biogenesis and centrosome duplication. PMID- 1934058 TI - Short inverted repeats at a free end signal large palindromic DNA formation in Tetrahymena. AB - Large palindromic DNAs are formed in many cell types, but their molecular mechanism is unknown. During nuclear differentiation in Tetrahymena, the ribosomal RNA genes (rDNA) are converted from a single integrated copy to an extrachromosomal head-to-head palindrome. Using in vitro mutagenesis and Tetrahymena transformation, we show that two properties of the rDNA are necessary and sufficient for palindrome formation. The first is a pair of 42 bp inverted repeats found at the rDNA's 5' end. Its inverted symmetry, but not specific sequence, is important. The second is a free end next to the repeats. It is normally created by chromosome breakage in vivo, but can also be provided by restriction endonuclease cutting before transformation. We also demonstrate that the ability to form palindromes is not restricted to developing nuclei, but is present in vegetative cells as well. This process may represent a general mechanism for palindrome formation in eukaryotes. PMID- 1934059 TI - HIV-1 Rev regulation involves recognition of non-Watson-Crick base pairs in viral RNA. AB - We have used an iterative in vitro genetic selection to identify the important structural features of the viral RNA element bound by the Rev protein of human immunodeficiency virus type 1 (HIV-1). Functional Rev-binding RNAs were selected from a pool of 10(13) variants of the wild-type Rev-binding domain. Bases conserved among the binding species define a 20 nucleotide core binding element. Covariation of some of these conserved bases indicates that the Rev-binding element is a stem-bulge-stem with a G:G base pair in the bulge. Mutational studies show that this non-Watson-Crick base pair is required for Rev binding in vitro and Rev responsiveness in vivo. We propose that the G:G base pair distorts the sugar-phosphate backbone of viral RNA and that this distortion is a critical determinant of recognition by Rev. PMID- 1934060 TI - Family of proteins that interact with TFIID and regulate promoter activity. AB - A family of proteins was shown to bind cooperatively with TFIID to core promoters, as previously demonstrated for the general initiation factor TFIIA. These factors form distinct complexes with TFIID, fail to bind DNA in the absence of TFIID, differ chromatographically from TFIIA, and compete with TFIIA for binding to TFIID. Our results suggest the formation of heterogeneous preinitiation complexes at the step involving TFIIA interactions. This establishes a molecular switch that regulates basal level transcription in vitro and has consequences for transcriptional activation by gene-specific activators. PMID- 1934061 TI - A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA. AB - LAP, a transcriptional activator, and LIP, a transcriptional repressor, are translated from a single mRNA species by using two AUGs within the same reading frame. These two proteins share the 145 C-terminal amino acids that contain the basic DNA-binding domain and the leucine zipper dimerization helix. Probably owing to its higher affinity for its DNA cognate sequences, LIP can attenuate the transcriptional stimulation by LAP in substoichiometric amounts. As revealed by transient transfection experiments, a moderate increase in the LAP/LIP ratio results in a significantly higher transcriptional activation of an appropriate target gene. The LAP/LIP ratio increases about 5-fold during terminal rat liver differentiation and is thus likely to modulate the activity of LAP in the intact animal. PMID- 1934062 TI - Identification of a protein required for disulfide bond formation in vivo. AB - We describe a mutation (dsbA) that renders Escherichia coli severely defective in disulfide bond formation. In dsbA mutant cells, pulse-labeled beta-lactamase, alkaline phosphatase, and OmpA are secreted but largely lack disulfide bonds. These disulfideless proteins may represent in vivo folding intermediates, since they are protease sensitive and chase slowly into stable oxidized forms. The dsbA gene codes for a 21,000 Mr periplasmic protein containing the sequence cys-pro his-cys, which resembles the active sites of certain disulfide oxidoreductases. The purified DsbA protein is capable of reducing the disulfide bonds of insulin, an activity that it shares with these disulfide oxidoreductases. Our results suggest that disulfide bond formation is facilitated by DsbA in vivo. PMID- 1934063 TI - Selective inhibition of transcytosis by brefeldin A in MDCK cells. AB - Treatment of most cells with brefeldin A (BFA) leads to the retrieval of the Golgi complex to the endoplasmic reticulum, presumably reflecting an inhibition of cytoplasmic coat protein binding to Golgi membranes. Although BFA has been thought to act only on biosynthetic organelles, we now show that this drug also reversibly blocks polymeric immunoglobulin receptor-mediated transcytosis in MDCK cells. The action of BFA on transcytosis was selective, since internalization, recycling, and intracellular degradation were unaffected. The block occurred early on the transcytotic pathway, probably before the translocation of IgA containing vesicles from the basal to the apical cytoplasm. Although BFA caused MDCK cell endosomes to become more tubular, the organization of the Golgi and binding of the 110 kd Golgi coat protein beta-COP was surprisingly unaffected. These results suggest that in MDCK cells, endocytic organelles contain a BFA sensitive coat that regulates their organization and function even though the Golgi coat is BFA resistant. PMID- 1934064 TI - A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells. AB - Cytolytic lymphocytes (CTLs) are characterized by their inclusion of cytoplasmic granules containing effector molecules such as perforin and the serine proteases. Here we describe the cDNA cloning and functional characterization of two related isoforms of a cytolytic granule protein designated TIA-1. Sequence analysis reveals that the 40 kd TIA-1 isoform (rp40-TIA-1) is structurally related to the poly(A)-binding proteins, possessing three RNA-binding domains and a carboxy terminal, glutamine-rich auxiliary domain. The 15 kd TIA-1 isoform, the major species present in cytolytic granules, appears to be derived from the carboxy terminal auxiliary domain of rp40-TIA-1 by proteolytic processing. Both natural and recombinant TIA-1 were found to induce DNA fragmentation in digitonin permeabilized thymocytes, suggesting that these molecules may be the granule components responsible for inducing apoptosis in CTL targets. PMID- 1934065 TI - Translocations, master genes, and differences between the origins of acute and chronic leukemias. PMID- 1934066 TI - Chromosome first aid. PMID- 1934067 TI - Molecular cross talk between epithelial cells and pathogenic microorganisms. AB - The conference brought together epithelial cell biologists and molecular microbiologists and emphasized that these seemingly diverse disciplines are intricately intertwined. The model systems discussed throughout the meeting emphasized the novel approaches available to address key issues and begin to understand the molecular details of responses triggered at the microbial epithelial interface. For example, co-crystallization of native ligand-receptor complexes as well as biologically or chemically altered forms of these complexes will allow fine details of receptor-ligand interactions to be determined. This approach is critical in development of new generation antimicrobial agents. Furthermore, transfection techniques that allow receptor expression in model epithelia, development of representative animal model systems, and development of transgenic mouse strains will aid in dissecting microbial-epithelial interactions and will provide further advances in studies on pathogenesis and tissue and host tropism. We are only beginning to uncover the nature of the bidirectional regulatory signals that occur between microbes and hosts. We know little about how these signals relate to the disease state, to microbial virulence, or to immune function. Clearly the cross talk between cell biologists and microbiologists is an important step in unraveling the events occurring between microbes and eukaryotic cells. PMID- 1934068 TI - Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. AB - We have conducted a genetic screen for mutations that decrease the effectiveness of signaling by a protein tyrosine kinase, the product of the Drosophila melanogaster sevenless gene. These mutations define seven genes whose wild-type products may be required for signaling by sevenless. Four of the seven genes also appear to be essential for signaling by a second protein tyrosine kinase, the product of the Ellipse gene. The putative products of two of these seven genes have been identified. One encodes a ras protein. The other locus encodes a protein that is homologous to the S. cerevisiae CDC25 protein, an activator of guanine nucleotide exchange by ras proteins. These results suggest that the stimulation of ras protein activity is a key element in the signaling by sevenless and Ellipse and that this stimulation may be achieved by activating the exchange of GTP for bound GDP by the ras protein. PMID- 1934069 TI - The Drosophila roughened mutation: activation of a rap homolog disrupts eye development and interferes with cell determination. AB - Roughened is a dominant mutation of D. melanogaster that disrupts eye development. The majority of the ommatidia in the adult eye lack a single photoreceptor cell, which is most commonly the R7 cell. The Roughened mutation disrupts the early stages of photoreceptor cell determination. Roughened is a dominant gain-of-function mutation that results from a single amino acid change (Phe157 to Leu) in the Drosophila Rap1 protein. Loss of function Rap1 mutations are lethal. Drosophila Rap1 protein is 88% identical to human rap1A/K-rev1 protein, a putative antagonist of ras action. PMID- 1934070 TI - New telomere formation after developmentally regulated chromosomal breakage during the process of chromatin diminution in Ascaris lumbricoides. AB - During the process of chromatin diminution, which takes place in all presomatic cells of the early Ascaris embryo, the heterochromatic termini of the chromosomes are lost. Here we show that the newly formed ends of the reduced somatic chromosomes carry tandem repeats of the telomeric sequence TTAGGC. Comparison of a cloned somatic telomere with the corresponding germline chromosomal region revealed that these telomeric repeats are not present at or near the chromosomal breakage site. They are most likely added by a telomerase-mediated event. Chromosomal breakage, which precedes the telomere addition process, takes place within a short, specific chromosomal region (CBR); however, it does not occur at a single locus, but rather at many different sites. Altogether, our data show that chromatin diminution in Ascaris is a complex molecular process that includes site-specific chromosomal breakage, new telomere formation, and DNA degradation. PMID- 1934071 TI - Developmentally programmed healing of chromosomes by telomerase in Tetrahymena. AB - Healing of a broken chromosome and in eukaryotes involves acquisition of a telomere. During macronuclear development in ciliated protozoans, germline chromosomes are fragmented into linear subchromosomes, whose ends are healed by de novo addition of telomeres. We showed previously that the ribonucleoprotein enzyme telomerase elongates preexisting telomeres by synthesizing one telomeric DNA strand, using a template sequence in the RNA moiety of the enzyme. By marking telomerase with a mutation in the telomerase RNA template, which causes synthesis of novel telomeric sequences, we now show that in the ciliate Tetrahymena, telomerase directly adds telomeric DNA onto nontelomeric sequences during developmentally controlled chromosome healing. Unexpectedly, one telomerase RNA template mutation converted telomerase from an enzyme that normally synthesizes precisely templated sequences to a less precise polymerase that sometimes synthesizes irregular telomeric repeats in vivo. PMID- 1934072 TI - Transduction of the IFN-gamma signal for HLA-DR expression in the promonocytic line THP-1 involves a late-acting PKC activity. AB - Interferon gamma (IFN-gamma) is the most potent known lymphokine for activating macrophages and has been shown to induce expression of HLA-DR in THP-1 cells, a monocytic tumor cell line which expresses many of the properties of monocytes, in a dose- and time-dependent manner. Experiments were designed to examine, by FACS analysis and by measurement of messenger RNA levels, the molecular mechanism regulating the expression of HLA-DR molecules. The expression of HLA-DR molecules induced by IFN-gamma was blocked by the protein kinase C (PKC) inhibitors sphingosine, staurosporine, and H7. H7 when added up to 20 hr after the initial stimulation with IFN-gamma prevented the further expression of HLA-DR. The general kinase inhibitors H8, H9, and HA1004, all less potent PKC inhibitors than H7, did not block the IFN-gamma-induced expression of HLA-DR at the concentrations employed. W7, a calmodulin antagonist, but not a PKC inhibitor, was also unable to prevent the IFN-gamma-induced expression of HLA-DR. Treatment of THP-1 with phorbol 12-myristate 13-acetate (PMA), a direct activator of PKC, alone or with Ca2+ ionophore A23187, was unable to induce HLA-DR expression. However, pretreatment with PMA for 24 hr prior to IFN-gamma stimulation decreased the IFN-gamma-induced expression of HLA-DR without decreasing IFN-gamma receptor levels. These results suggest that PKC plays a significant role in the IFN-gamma induced signal transduction pathway leading to the expression of HLA-DR in cells of the mononuclear phagocytic lineage, and that PKC activity is required throughout the course of events leading to the actual expression of HLA-DR. PMID- 1934073 TI - Interactions of bone marrow cells from young and old mice with syngeneic and allogeneic thymic tissue. AB - Age-related changes manifested in MHC-linked recognition of bone marrow (BM) cells by the thymic stroma were studied in vitro model of thymus-BM chimeras. Fetal thymuses (FT) depleted of self-lymphocytes were colonized with BM cells from syngeneic and allogeneic donor mice. When cells from young (3-month-old) or old (24-month-old) donors syngeneic to the stroma were seeded in a mixture with cells of allogeneic young origins (C57BL/6J-Thy1.2 and ARK/J-Thy1.1 seeded onto C57BL/6J FT), the syngeneic cells showed an age-related developmental advantage. Accordingly, cells from the old syngeneic mice manifested a significantly reduced capacity to compete with allogeneic cells when compared with the young syngeneic cells. When allogeneic BM cells from young or old mice were seeded onto the thymic stroma in a mixture with BM cells from young donors syngeneic to that stroma (BALB/c-Thy1.2 mixed with C57BL/Ka-Thy1.1 seeded onto C57BL/6J or C57BL/Ka FT), the Thy1+ cells which developed were mainly of syngeneic origin. The age of the allogeneic cells had no significant effect on the results. However, when old allogeneic cells were mixed with old syngeneic cells, the developmental advantage of the syngeneic cells was not manifested. When seeding of allogeneic cells was followed 1 day later by seeding of syngeneic cells, the syngeneic advantage was eliminated, suggesting that the MHC-linked competition began during the first 24 hr of contact with the thymic tissue. When BM-derived thmocytes grown in FT explants were transferred onto second FT recipient explants of the same genotype as the first ones, the syngeneic advantage was abolished, suggesting either that the thymic microenvironment was modified as a result of colonization or that it induced a change in the BM cells. In this respect, the young allogeneic BM derived thymocytes showed a significant advantage when compared with the old cells. Thus, the MHC-linked syngeneic preference in the early development of BM cells is also manifested in aging mice, yet at a level that is significantly reduced compared with that seen in the young mice. PMID- 1934074 TI - Theiler's virus infection induces a specific cytotoxic T lymphocyte response. AB - Theiler's virus, a murine picornavirus, persists in the central nervous system of susceptible mouse strains and causes chronic inflammation and primary demyelination. One of the current hypotheses is that demyelination is, at least in part, mediated by virus-specific cytotoxic T lymphocytes (CTL). However, it is generally assumed that picornaviruses do not induce CTL. In point of fact, their existence has only been demonstrated for Coxsackievirus B-3. To determine whether Theiler's virus induces a CTL response, we generated a murine mastocytoma cell line stably transfected with the coding region of the genome of Theiler's virus strain DA. Using these cells as targets we showed that infected DBA/2 mice, a susceptible strain, produce cytotoxic T lymphocytes. The cytotoxic activity was Theiler's-virus specific. It was for the most part mediated by CD8+ T lymphocytes and H-2 restricted. This is the first demonstration that a specific CTL response is generated during Theiler's virus infection. PMID- 1934075 TI - Ultraviolet light-induced increase in tumor cell susceptibility to TNF-dependent and TNF-independent natural cell-mediated cytotoxicity. AB - Previously we demonstrated that two consecutive in vitro irradiations of MCA 102 cells with high doses of UVC light (610 and 457 J/m2) resulted in a selection of a permanent line MCA 102UV that manifested high sensitivity to natural cell mediated cytotoxicity (NCMC). In the present study analysis of the effector cells involved in lysis of these tumor cells was performed by comparing the cytotoxicity of normal spleen cells which mediated both NK and NC cell activity with (a) normal spleen cells in which NC activity was neutralized by anti-TNF Abs (NK+,NC-), (b) NK-depleted or NK-deficient spleen cells (NK-,NC+), and (c) NK deficient or -depleted spleen cells with NC activity neutralized by anti-TNF Abs (NK-,NC-). Results of these studies indicate that lysis of the original MCA 102 tumor cells was relatively low and was mediated by NC cells. UV irradiation significantly increased MCA 102 tumor cell sensitivity to lysis by both NK and NC cells. Analysis of the mechanisms involved in UV-induced NK sensitivity revealed that UV irradiation increased tumor cell susceptibility to lytic NK-derived granules. NC sensitivity of MCA 102UV tumor cells was associated with their increase in sensitivity to TNF and selection of MCA 102UV cells for resistance to rTNF resulted in a decrease in their susceptibility to NC cells. To determine how fast UV-induced sensitivity to NCMC and rTNF can be established, 51Cr-labeled MCA 102 cells were irradiated in vitro with 38-304 J/m2 of UVC light and their sensitivity to lysis by spleen cells and rTNF was tested immediately in an 18-hr cytotoxicity assay. UV treatment with the same doses was repeated 12 days later. The data obtained showed that tumor cell sensitivity to NCMC and TNF appeared shortly after UV irradiation, was stable, and was further substantially augmented by the second round of UV treatment. Thus, in vitro UV irradiation of tumor cells could be an effective modulator of tumor cell sensitivity to TNF-dependent and TNF-independent cell-mediated cytotoxicity. PMID- 1934076 TI - Altered lymphocyte populations in sphha/sphha mice with chronic hemolytic anemia. AB - Lymphocyte kinetics and phenotype were examined in mutant anemic sphha/sphha mice that manifest a lifelong lymphocytosis which accompanies their chronic hemolytic anemia. Anemic mice have significant increases in CD4+, CD8+, and sIgM+ lymphocytes in peripheral blood. Pulse and continuous infusion studies with [3H]TdR suggest that this apparent lymphoid expansion is not due to increased production of lymphocytes in bone marrow or thymus but rather to a redistribution of lymphocytes from the spleen to other peripheral lymphoid tissue sites as well as increased proliferation of T and B lymphocytes in lymph nodes. This murine model could be useful to examine lymphocyte perturbations that may accompany chronic hemolytic anemia in humans. PMID- 1934077 TI - Serum IgG from CBA/K1Jms-lprcg/lprcg mice induces interleukin 3 in an interleukin 3-dependent cell line--possible correlation with lymphadenopathy. AB - Serum IgG of CBA-K1Jms-lprcg/lprcg (lprcg/lprcg) mice with spontaneous systemic lymphadenopathy supported the proliferation of an IL-3-dependent cell line, FDC P2/185-4. The lprcg/lprcg IgG induced IL-3 synthesis in FDC-P2/185-4 cells, and cells grew by an autocrine mechanism. There was virtually no time lag between the appearance of lymphadenopathy and an increase of IL-3-inducing activity in the sera. We have previously shown that serum IgG from other autoimmune mice with lymphadenopathy, MRL/Mp-lpr/lpr(MRL/lpr) and C3H/HeJ-gld/gld(C3H/gld), also induces IL-3 synthesis and cell growth in FDC-P2/185-4 cells. Furthermore, neither F1 (lprcg/+) mice between lprcg/lprcg and CBA(-)+/+ nor those (lpr-gld) between C3H-lpr/lpr and C3H/gld showed such IL-3-inducing activity, while those (lprcg-gld) between lprcg/lprcg and C3H/gld showed activity much lower than that of their parental strains but significantly higher than that of normal CBA(-)+/+ mice. This result is consistent with the incidence and degree of lymphadenopathy in these F1 mice. Our results suggest that expression of IgG(s) with cytokine inducing activity might be controlled by these mutant genes, lpr, gld, and lprcg, and might be related to lymphadenopathy in these mice. PMID- 1934078 TI - Control of DNA replication in a transformed lymphoid cell line: coexistence of activator and inhibitor activities. AB - Proliferating lymphocytes contain an intracellular factor, ADR (activator of DNA replication), which can initiate DNA synthesis in isolated quiescent nuclei. Resting lymphocytes lack ADR activity and contain an intracellular inhibitory factor that suppresses DNA synthesis in normal but not transformed nuclei. In this study we describe a MOLT-4 subline that produces both the activator and inhibitory activities which can be separated by ammonium sulfate fractionation. The inhibitor is heat stable and inhibits ADR-mediated DNA replication in a dose dependent manner. It does not inhibit DNA polymerase alpha activity. The inhibitor must be present at the initiation of DNA replication to be effective, as it loses most of its effectiveness if it is added after replication has begun. The presence of inhibitory activity in proliferating MOLT-4 cells, taken with the previous observation that inhibitor derived from normal resting cells does not affect DNA synthesis by MOLT-4 nuclei, suggests that failure of a down-regulating signal may play an important role in proliferative disorder. PMID- 1934079 TI - Analysis of class II MHC structure in thymic nurse cells. AB - During the course of thymocyte maturation, the processes of positive selection and tolerance induction are mediated by interactions between thymocyte T-cell receptors and MHC molecules on thymic stromal cells. The means by which these seemingly contrary processes can be mediated by interactions between the same molecules has long been a source of controversy. One idea which has been put forward is that the MHC molecules in different microenvironments of the thymus are not the same. We have tested this hypothesis by examining class II transcripts derived from thymic cortical epithelial cells known as thymic nurse cells, reasoning that alternative splicing of primary transcripts might give rise to a positively selecting MHC molecule. However, we found no evidence for alternative splicing of these transcripts. These results are presented and discussed with regard to implications for possible mechanisms of positive selection. PMID- 1934080 TI - Tumourigenesis: a malignant scenario. PMID- 1934081 TI - Involvement of carbohydrates in the hardening of the zona pellucida of mouse oocytes. AB - The effect of lectins with different saccharide specificity (ConA, LCA, DBA, WGA and PNA) on enzymatic digestion of the zona pellucida (ZP) of mouse oocytes was studied. All lectins tested, except PNA, induced ZP hardening with different degrees of efficiency. Moreover, extensive ZP digestion with mixed exoglycosidase prevented "spontaneous" ZP hardening. These observations suggest that changes of the carbohydrate moieties can be involved in the hardening of the zona pellucida of mouse oocytes. PMID- 1934083 TI - F-actin contractile rings in protoplasts of the yeast Schizosaccharomyces. AB - By rhodamine-phalloidin fluorescence, distinct continuous F-actin rings were visualized in 18-20% of the protoplasts of Schizosaccharomyces pombe and S. japonicus var. versatilis, in addition to randomly distributed F-actin dots. Whereas the reversion of ring-lacking protoplasts coincided with the polarization of the dotted F-actin pattern, the ring-containing protoplasts became furrowed as the F-actin rings constricted. The furrowing was more conspicuous in S. japonicus var. versatilis than in S. pombe protoplasts and it was blocked when the reversion was inhibited by Novozyme 234 indicating that the cell wall formation is essential for the F-actin ring constriction. PMID- 1934082 TI - Effect of canatoxin on cell cultures. AB - Canatoxin, a toxic protein isolated from Canavalia ensiformis, was shown to inhibit DNA synthesis and to produce a cytolytic effect when added in vitro to various cells, in doses ranging from 50 to 500 nM. In this case no selectivity was found for a certain cell type, as both normal and transformed cells could be affected by the toxic protein. The cytostatic effect was irreversible upon removal of the toxic protein from the medium and could be fully attained after exposing the cells to canatoxin for only 30 min. The use of an in vitro cell culture system may allow for a better insight on the mode of action of canatoxin. PMID- 1934085 TI - F-actin bundling protein from Physarum polycephalum: purification and its capacity for co-bundling of actin filaments and microtubules. AB - An F-actin bundling protein was isolated and purified from plasmodium of Physarum polycephalum. The F-actin bundling protein in Physarum extract was passed through a DEAE-cellulose column. After the protein in the fraction was treated with 6 M urea, it was purified by gel filtration on Sephacryl S-300 HR followed by chromatography on CM-Toyopearl (cation exchange) in the presence of 6 M urea. The purified protein gave a single band on SDS-PAGE, and the molecular weight was estimated to be 52,000. This F-actin bundling protein is referred to as the 52 kDa protein. Interestingly, the 52 kDa protein also induced bundling of microtubules. The formation of F-actin and microtubule bundles was Ca(2+) insensitive, but depended on the salt concentration. Each bundle formed at NaCl concentrations less than 0.1 M. The 52 kDa protein cross-reacted with monoclonal antibody raised against a HeLa 55 kDa protein (an F-actin bundling protein from HeLa cells) (Yamashiro-Matsumura and Matsumura: J. Biol. Chem. 260:5087-5097, 1985). When the 52 kDa protein was added to a mixture of actin filaments and microtubules, co-bundles composed of both filaments formed. This is the first reported example in which an F-actin bundling protein induced co-bundling of actin filaments and microtubules. PMID- 1934084 TI - Ultrastructure of the human erythrocyte cytoskeleton and its attachment to the membrane. AB - We attached paraformaldehyde-fixed human erythrocyte ghosts to coated coverslips and sheared them to expose the cytoskeleton. Quick-freeze, deep-etch, rotary replication, or tannic acid/osmium fixation and plastic embedding revealed the cytoskeleton as a dense network of intersecting straight filaments. Previous negative stain studies on spread skeletons found 5-6 spectrin tetramers intersecting at each actin oligomer, with an estimated 250 such intersections/microns 2 of membrane. In contrast, we found 3-4 filaments at each intersection and approximately 400 intersections/microns 2 of membrane. Immunogold labeling verified that the filaments were spectrin, but their lengths (29-37 nm) were approximately one-third that of extended spectrin dimers. The length and diameter of the filaments were sufficient to accommodate spectrin dimers, but not spectrin tetramers. Our results suggest that, in situ, spectrin dimers may associate as hexamers and octamers, rather than tetramers. We present several explanations that can reconcile our observations on intact cytoskeletons with previous reports on spread material. Extracting sheared ghosts with solutions of low ionic strength removed the cytoskeleton to reveal projections from the cytoplasmic surface of the membrane. These projections contained band 3, as shown by immunogold labeling, and they aggregated to a similar extent as intramembrane particles (IMP) when the cytoskeleton was removed, suggesting a direct relationship between these structures. Quantification indicated a stoichiometry of 2 IMP for each cytoplasmic projection. Cytoplasmic projections presumably contain other proteins besides band 3 since further treatment with high ionic strength solutions extracts peripheral proteins and reduces the diameter of projections by approximately 3 nm. PMID- 1934086 TI - Comparative kinetics of short and long sperm in sperm dimorphic Drosophila species. AB - All species of the Drosophila obscura group exhibit within-ejaculate sperm length dimorphism. The present work is a contribution to the understanding of sperm competition through a comparative study of sperm kinetic parameters in four of these species. Videomicrographic observations at 200 frames per second of sperm from males and females, out of the storage organ, prior or after storage were made. Drosophila sperm display both major and minor waves. The former is analysed by measuring coiling diameter (micron) and the latter by recording both beat frequency (s-1) and wave propagation velocity (micron.s-1). Results show that the 'behaviour' of short and long spermatozoa noticeably differ: short sperm kinetics remains unaltered after storage while both major and minor waves of long spermatozoa are markedly modified. Thus, evidence is provided here of a sort of "differential activation" which is assumed to result in different survival abilities of short and long sperm within the storage organ of females. PMID- 1934087 TI - Mucosal penetration enhancers for facilitation of peptide and protein drug absorption. PMID- 1934089 TI - Functional aspects of mammalian neural transplantation. AB - Although initially perceived as a method to study neural development and regeneration, neural transplantation has recently become a very promising approach in its own right as a therapeutic tool to treat neurodegenerative disorders. The development of several animal models which mimic aspects of clinical disorders such as Parkinson's disease, Alzheimer's disease, and Huntington's chorea, provides systems in which to study the potential benefits of grafts derived from different sources. Both fetal and adult donor tissues presently are under investigation. Additionally, cell lines and genetically engineered cells also are being developed as suitable graft material. Important aspects of graft-host interaction, including cell survival, host regeneration, immune interactions, improved behavior, and blood-brain barrier phenomena, may be studied in these transplant models. Advances in this field of biomedical research have led to clinical trials in patients afflicted with Parkinson's disease who now are undergoing transplantation therapy. Thus far, the results have been equivocal, raising important ethical questions about continued clinical studies until more is understood about how neural transplants function and interact with the host. Nevertheless, neural transplantation holds tremendous promise as a future therapeutic tool to treat progressive and irreversible neural disorders. PMID- 1934088 TI - Patterns of antigenic expression of human glioma cells. AB - Gliomas are known to express over a hundred antigens, and no doubt make many more unknown antigens. Major categories of glioma cell antigens include glial antigens, ECM antigens, muscle antigens, melanoma antigens, "tumor-specific" antigens, and cellular proliferation antigens. A strikingly low number of cultured gliomas express glial antigens. They commonly express not only ectodermal, but also mesenchymal ECM antigens. Tumor-specific antigens have been an elusive goal of neuro-oncologists, but there are bright new prospects in need of further study. These include direct screening of hybridoma supernatants on glioma tissue and targeting glycolipids, glycoproteins, and oncogene products. Cellular proliferation antigens will become increasingly important in predicting prognosis of gliomas. Proliferation antigens of cultured gliomas are under intense scrutiny at present. The extent and evolution of antigenic heterogeneity of neoplastic cells in gliomas raise basic biologic questions with profound clinical ramifications. Individual glioma cell lines may generate more than 30 subtypes of cells with minor to major differences in antigen expression. These include expression of antigens representing multiple different cell lineages. Mesenchymal drift is the tendency of gliomas to progressively lose glial and gain mesenchymal features. Models of in vivo mesenchymal drift occur in glioma cell culture where mechanisms are more easily investigated than in situ. Neither exogenous protein absorption nor fibroblast overgrowth explain the phenomenon. Cells with the mesenchymal marker, fibronectin, overgrow GFAP-positive cells during explanation of gliomas. Many of these fibronectin-positive cells express cytologic and growth characteristics of neoplasia. The source of these cells is unknown. A leading candidate for the source of these neoplastic fibronectin positive cells is the proliferation of vascular and mesenchymal cell elements of glioma tissue commonly called "endothelial proliferations". However, these elements in tissue do not display the same abnormalities of neoplasia as the fibronectin-positive cells in culture. Understanding this "tissue/explant paradox" may solve the conundrum of mesenchymal drift. In the absence of a counterpart in tissue of these neoplastic fibronectin-positive cells so abundant in glioma cell cultures, mechanisms of mesenchymal drift other than overgrowth of neoplastic mesenchyme must be considered. The occurrence of "dual cells" which express antigenic markers of entirely different cellular lineages suggests the possibility that neoplastic glia generate mesenchymal drift by altered gene expression. Various studies which suggest the capacity of cultured gliomas to alter phenotypic expression of their genes are critically examined and their relevance to mesenchymal drift discussed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1934090 TI - Neurological consequences of protein and protein-calorie undernutrition. AB - Malnutrition is a worldwide problem of enormous magnitude. The growth of the central nervous system in human beings is retarded in case of malnutrition in the very early part of life. Likewise, the peripheral nerves in infants and children and young growing animals appear susceptible to nutritional deprivation including protein as well as protein-calorie deficiency. Motor weakness, hypotonia, and hyporeflexia in infants and children are the essential clinical neurological signs in protein-calorie malnutrition (PCM). Motor and sensory nerve conduction are significantly impaired in children with PCM as well as in animals subjected to protein or protein-calorie deficiency. Histological studies have revealed reduced diameter of myelinated nerve fibers, retardation of myelination, segmental demyelination and remyelination, axonal degeneration, and shortened longitudinal growth of internodes. Diffusion barrier by perineurium may be broken. There is reduction in myelin lipids and impaired synthesis of myelin as shown by the biochemical and radioisotope incorporation studies. Presence of cholesterol esters in the biochemical synthesis of nerves suggests degeneration changes. Experimental studies have revealed that most effects of PCM on peripheral nerves can be reversed by nutritional rehabilitation, although complete recovery in the sensory nerve action potential, fiber size of dorsal nerve roots, and myelin-specific lipids does not occur. Skeletal muscle also shows many changes including muscle fiber atrophy, reduction in duration and amplitude of motor unit potentials, and/or fibrillation on electromyography (EMG) and biochemical estimation of muscle enzymes. These changes may be the reflection of a direct effect of PCM on muscles or secondary to the abnormal structural or biochemical changes in the peripheral nerves. PCM affects the central nervous system, especially the neuropsychological functions, in a lasting manner. Learning deficits and impairment of manual dexterity are the most obtrusive features. Neurotransmitter abnormalities and maturation lag in electroencephalogram have been demonstrated in experimental animals. Spinal cord dysfunction sometimes manifests overtly as clinical myelopathy. Degenerative changes in the cerebellum have been noted. PMID- 1934091 TI - Current concepts and recent advances in the athlete's shoulder. AB - The demands placed on the shoulder girdle during athletics can often exceed its physiologic limits and result in significant injury. The goal of orthopedists, therapists, trainers, and ancillary personnel who care for athletes involved in sports which require extreme demands of the shoulder is to enhance athletic performance, extend their longevity, and prevent injury. With the new concepts available from basic science and clinical research, a clear understanding of normal architecture and biomechanical function of the shoulder girdle is better appreciated. A greater understanding of sporting activities and their physiologic demands on the shoulder are also more clear. The future of all this research seems to be pointing toward maintenance and restoration of normal anatomy and physiology about the shoulder girdle. PMID- 1934092 TI - Basic science and clinical application in the athlete's shoulder. PMID- 1934093 TI - Classification and definition of tendinopathies. AB - The authors have classified tendinopathies into two categories. The majority of the tendinopathies are in the primary category in which lesions arise in the substance of the tendon. The authors emphasize that not all tendinopathies are degenerative in nature. Some primary tendinopathies are reactive, such as calcifying tendinitis. PMID- 1934095 TI - Ligamentous control of shoulder stability based on selective cutting and static translation experiments. AB - The glenohumeral joint is a complex articulation with little inherent stability, capable of significant rotations. The capsuloligamentous structures play a critical static role in maintaining joint stability. Various components have been identified both anatomically and functionally, with their contributions varying depending on joint position and the direction of applied forces. PMID- 1934094 TI - Imaging techniques of the shoulder: present perspectives. AB - Through its ability to evaluate the individual components of the rotator cuff, the labral-capsular complex, the subacromial and subdeltoid spaces, and the glenoid, humerus, clavicle, and acromion, MRI provides a means of comprehensively evaluating the shoulder. Further advances in the use of intra-articular MRI contrast agents will undoubtedly enhance the role of MRI in the evaluation of subtle labralcapsular pathology. Although they are experimental, kinematic studies of the shoulder may provide valuable insight into the pathogenesis of disorders such as impingement syndrome. The ability of MRI to provide detailed pathologic information about individual components of the shoulder, particularly the rotator cuff, presents a challenge to shoulder surgeons. Patient symptomatology should be correlated with MRI findings and the clinical significance attached to different pathologies reevaluated. Through rigorous confirmation of MRI findings, dedicated therapeutic algorithms can be established based on detailed clinicopathologic data. Present and future surgical and nonsurgical management of the shoulder will undoubtedly be shaped by MRI. PMID- 1934096 TI - Mechanics of glenohumeral instability. AB - The glenohumeral joint is designed for mobility and is normally lax. It is stabilized in its midrange by its limited joint volume and concavity-compression. It is stabilized at the extremes of motion by its ligaments. An enhanced understanding of these stabilizing mechanisms helps us in the diagnosis and management of glenohumeral instability. PMID- 1934097 TI - Electromyographic analysis of muscle action about the shoulder. AB - The application of dynamic integrated EMG and motion analysis to the shoulder has improved the understanding of dynamic shoulder biomechanics during athletic activities and rehabilitation protocols. These studies exemplify a symbiotic merger of basic science research and clinical application. EMG and motion analysis has produced specific objective quantifiable data concerning the muscles in and about the shoulder during normal planar motion, athletic motions, and rehabilitation exercises. This expanded understanding of intricate muscular interrelationships during athletic activities and rehabilitative exercises has not only complemented clinical awareness of subtle shoulder anomalies but helped to develop logical preventative exercises, surgical procedures, and rehabilitation protocols, all of which are based on sound scientific principles. Comprehension of the normal intermuscular interdependence during the previously mentioned activities has led us to investigate common athletic shoulder disorders. It is hoped that application of the normal EMG and motion analysis to the pathologic state will enable us to suggest new ideas concerning the pathomechanics of these disorders, as well as propose future treatment and rehabilitation of these maladies. The specific emphasis in this article has been the role of integrated EMG and motion analysis in the evaluation of athletic activities and rehabilitation exercises. It is hoped that knowledge of these investigations will increase the clinician's basic understanding of the biomechanics of the shoulder and aid in his or her clinical evaluation, treatment, and subsequent rehabilitation of the shoulder. PMID- 1934098 TI - The vascularity of the rotator cuff. AB - The major arterial supply to the rotator cuff is derived from the ascending branch of the anterior humeral circumflex artery, the acromial branch of the thoracoacromial artery, as well as the suprascapular and posterior humeral circumflex arteries. The pathogenesis of rotator cuff tears has been considered to be influenced by the microvascular supply of the rotator cuff tendons. Most cadaver studies have demonstrated a hypovascular area within the critical zone of the supraspinatus tendon. It has been suggested that this area of hypovascularity has a significant role in the attritional degeneration of the aging tendon. More recent studies of the microvascular supply to the supraspinatus tendon in symptomatic patients with impingement syndrome suggest that in the area of greatest impingement, i.e., the critical zone, there is actually hypervascularity. In contrast to the cadaver investigations, these studies seem to imply that hypervascularity or neovascularization is associated with symptomatic rotator cuff disease secondary to mechanical impingement. PMID- 1934099 TI - The relationship of acromial architecture to rotator cuff disease. AB - Variations in the architecture of the coracoacromial arch can lead to a clinically symptomatic rotator cuff lesion. Differences in the development and morphology of the acromion, and the presence of anterior acromial spurs and inferior acromioclavicular osteophytes decrease the volume of the subacromial space, leading to impingement. Recent anatomic, radiographic, biomechanical, and SPG studies have confirmed these architectural variations and their effects on the contents of the subacromial space. Abnormal contact between the acromion and these soft tissues can lead to pathologic lesions. Surgical procedures should be directed at increasing the space beneath the coracoacromial arch to reduce wear on the rotator cuff. PMID- 1934100 TI - Special shoulder problems in the throwing athlete: pathology, diagnosis, and nonoperative management. AB - Shoulder problems in the overhead and throwing athlete can result in rotator cuff tendinitis. Biomechanically, there is a delicate balance between mobility and stability of the shoulder complex. Repetitive overhead stressful motion can lead to overuse tendinitis, subtle instability, labral changes, and eventual fiber failure of the rotator cuff. Secondary impingement symptoms are commonly present. An accurate diagnosis along with an early and aggressive rehabilitation program is essential in the treatment of these athletes. PMID- 1934101 TI - Advances in the understanding of anterior instability of the shoulder. AB - Anterior instability involves a spectrum of disease ranging from the obvious acute first-time dislocation to the athlete presenting with shoulder pain and no history suggestive of instability. It is important to recognize the pathophysiology and how it relates to this spectrum of disease. The arthroscope has helped to identify the underlying pathology in both acute and chronic situations. Diagnostically, a history of a painful shoulder, especially in the athlete, should suggest anterior instability. Tests of translation, apprehension, and the use of local anesthetic can be useful. Arthroscopy is used in situations in which the diagnosis is unclear. The management of anterior instability should emphasize strengthening of the rotator cuff and scapular stabilizers. Surgical repair requires correction of the underlying pathology with minimization of damage to other structures. Arthroscopic management of anterior instability includes repair, debridement of intra-articular lesions, and the possibility of acute correction of the pathoanatomic lesions. PMID- 1934102 TI - Recent advances and perspectives on arthroscopic stabilization of the shoulder. AB - The goal of surgical stabilization of the unstable glenohumeral joint is to produce a stable yet mobile joint that can return to preinjury function. Open surgical procedures (in particular, the Bankart procedure) have evolved to a point where stability and mobility are being attained with a low complication rate, but the rate of return to preinjury function, particularly in overhead athletes, has not been ideal. Arthroscopic stabilization is an attractive alternative to open procedures, particularly in those patients who have a history of traumatic and unidirectional recurrent dislocations with a labral detachment. A variety of techniques for reattaching a detached labro-ligamentous complex have been described. Longer follow-up is needed to assess the efficacy of these procedures fully, particularly in light of the good results now being obtained with the open Bankart procedure. Longer-term studies have shown a higher rate of recurrence of dislocation with the arthroscopic technique than with the open technique. Arthroscopic stabilization offers the potential advantages of shorter hospitalization, less traumatic treatment of the soft tissues, more thorough examination of the glenohumeral joint and subacromial bursa, and greater cosmesis. It could also provide a means by which selective stabilization of those initial anterior dislocations that might be prone to recurrence could be performed. Long-term follow-up and randomized studies comparing open and arthroscopic techniques are needed to further define the best role of arthroscopic shoulder stabilization and to determine which of the several techniques described provides the best results with the fewest complications. PMID- 1934103 TI - An appreciation of posterior instability of the shoulder. AB - Fortunately, posterior instability of the shoulder is a relatively uncommon occurrence in the athlete. Acute traumatic posterior dislocations can be readily managed by conservative measures. Recurrent posterior subluxation, however, represents a more challenging problem for the orthopedic surgeon. As has been discussed, most patients with this disorder respond to nonsurgical treatment including physical therapy and modification of the offending activities. Should these modalities fail, operative treatment may be necessary. Careful assessment of the patient to rule out the associated presence of excessive ligamentous laxity or a voluntary component to the instability is mandatory. Pain is clearly the principal indicator for surgical treatment. Painless subluxation, either voluntary or involuntary, should first be treated conservatively. The surgical options discussed in this article range from simple soft-tissue repair to more complex osteotomies with combined capsular plication. It is important that the procedure be appropriate to the pathology. We do not believe that one technique alone can address all variants of posterior instability. Most instances of recurrent posterior subluxation represent unidirectional instability in patients with otherwise normal bony morphology. In these patients, a posterior capsulorrhaphy combined with appropriate immobilization should be effective. In select instances, when either excessive glenoid retroversion or deficiency is encountered, a glenoid osteotomy and posterior capsulorrhaphy have proved successful. This technique, more than any other, carries a number of potential technical pitfalls and should be employed cautiously. Multidirectional posterior instability, now a well-recognized entity, requires a different surgical approach -the capsular shift. Designed to address the inferior redundancy, as well as posterior laxity, this procedure is applicable to the multidirectional posterior subluxator. In conclusion, posterior instability of the athlete's shoulder is an increasingly recognized entity. Most instances are amenable to nonsurgical care. Should surgical treatment be necessary, optimal results may be achieved by careful attention to patient assessment, instability categorization, determination of the presence of ligamentous laxity, and appropriate surgical technique. PMID- 1934104 TI - Labral tears in throwing and racquet sports. AB - Throwing and overhead racquet motion is stressful activity that places great physical demands on the athlete's shoulder. This article focuses on glenoid labral tears as a consequence of this dynamic activity. These labral lesions may be present as an isolated entity or may be in association with glenohumeral instability. PMID- 1934105 TI - Arthroscopic management of the throwing athlete's shoulder: indications, techniques, and results. AB - This article briefly describes the various pathologic lesions seen in the throwing athlete's shoulder. The pathologic conditions discussed include primary and secondary impingement, tensile lesions of the rotator cuff and biceps-labral complex, glenohumeral laxity, labral tears, and AC joint injuries. Mechanism of injury, indications, and arthroscopic management of these lesions are discussed. PMID- 1934106 TI - Open surgical techniques in the athlete's shoulder. AB - Treatment of the athlete's shoulder is one of the greatest challenges facing the orthopedic specialist. Surgical procedures, and in particular, the open surgical techniques presented in this article, are always a last resort of treatment. The primary treatment is always nonoperative with a particular emphasis toward physiotherapy. In selected instances in which patients have failed rehabilitation, the techniques that are presented can achieve a relatively high degree of success if particular attention is paid to the specific indications, approaches, and details of each technique. Open surgical techniques for rotator cuff tendonitis, instability, and unusual problems in the athlete's shoulder are presented. PMID- 1934107 TI - Basic science and clinical application in the athlete's shoulder. A preventative program focusing on the glenohumeral joint. AB - This program can be implemented as either a preventative program or a rehabilitative program for the upper extremity in the throwing athlete or in nonthrowing athletes involved in overhead activities. The authors have found this program to be easily employed in a university setting. The keystone to its effectiveness is the participating individual. For optimal results, it should be performed as specifically outlined. The likelihood that shoulder symptomatology will develop is higher now that more people are participating in recreational and team sports for cardiovascular fitness. It is, therefore, imperative that a preventative program be developed in both the recreational and professional athletic population. PMID- 1934108 TI - Ethanol improves the transformation efficiency of intact yeast cells. AB - A technique is described in which ethanol is used to improve the genetic transformation of intact yeast (Saccharomyces cerevisiae) cells pretreated with LiAc and PEG. Transformation efficiency was increased with increasing concentrations of ethanol with a peak at 10% concentration. The effect varies with different yeast strains and plasmids and up to a maximum of a 15-fold increase was observed. PMID- 1934109 TI - Nuclear factors which bind to Dictyostelium discoideum transfer RNA genes. AB - RNA Polymerase III transcription factors from the cellular slime mold Dictyostelium discoideum were characterized, based on their stable binding to isolated tRNA genes. Different protein complexes are sequestered on DNA fragments containing tRNA genes depending on the conditions by which the nuclei were extracted. Binding specificity was determined through competition assays using competitor tRNA genes from the same gene family, from different gene families and from truncated tRNA genes. The complex with the highest multiformity of interdependent proteins is able to assemble with low affinity on a B-block-free tDNA template, whereas most lower molecular weight complexes require the presence of an intact B-block promoter element in order to assemble. PMID- 1934110 TI - Sequences of three dsRNAs associated with La France disease of the cultivated mushroom (Agaricus bisporus). AB - La France disease of the cultivated mushroom, Agaricus bisporus, is known to be associated with the presence of a number of dsRNA segments. The nucleotide sequences of the dsRNAs M2 (1.3 kb), M1 (1.55 kb) and L3 (2.8 kb), invariably associated with the disease, were determined. Putative coding sequences for proteins with molecular weights of 38, 40 and 87 kDa were found for M2, M1 and L3 dsRNAs, respectively. The average G + C content of these dsRNAs was 43%, close to that of A. bisporus nuclear DNA. The nucleotide sequences, as well as the amino acid sequences, appear to be unique, as no matching sequences could be found among databases. S3 dsRNA (0.39 kb), which is occasionally found in large amounts in diseased mushrooms, is an internally deleted variant of M2 dsRNA and is largely composed of the non-coding ends of that dsRNA. PMID- 1934112 TI - Genome analysis of imperfect fungi: electrophoretic karyotyping and characterization of the nuclear gene coding for glyceraldehyde-3-phosphate dehydrogenase (gpd) of Curvularia lunata. AB - The gene coding for glyceraldehyde-3-phosphate dehydrogenase (gpd) has been isolated from a genomic library of the filamentous fungus Curvularia lunata. The coding region of this gene consists of 1014 nucleotides and is interrupted by four introns. The gpd gene product shows a high degree of sequence identity with the corresponding proteins of various species belonging to both taxonomically related (e.g., Aspergillus nidulans), as well as more divergent, taxa. Using contour-clamped homogeneous electric field (CHEF) gel electrophoresis eight distinct chromosomal bands have been resolved, with two bands migrating as doublets and one as a triplet. Thus, the total number of chromosomes of C. lunata appears to be 12. The size of the chromosomes ranges from about 1.4 Mb to 4.0 Mb allowing an estimation of the genome to be approximately 29.7 Mb. By hybridization of fractionated chromosomes the gpd gene and the rDNA locus have been localized on individual chromosomes. PMID- 1934111 TI - Cloning the REC1 gene of Ustilago maydis. AB - The REC1 gene of Ustilago maydis plays a key role in homologous recombination and the repair of damaged DNA. In order to understand the nature and functions of the gene product, the gene has been cloned by functional complementation. A 3.8 kb cloned fragment complements the pleiotropic mitotic phenotype of different rec1 alleles. It does not complement the UV sensitivity of two other sensitive mutants. Disruption of the chromosomal copy of the 1.566 kb open reading frame within this fragment reproduces the rec1 pleiotropic phenotype. Furthermore, in diploids this disrupted reading frame is unable to complement previously characterised rec1 alleles. PMID- 1934113 TI - Sequences of two rbcS cDNA clones of Batophora oerstedii: structural and evolutionary considerations. AB - Two cDNA clones for the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (SSU) of Batophora oerstedii were isolated and sequenced. One clone contains the coding information for the complete SSU precursor protein. As in two other species of Dasycladaceae (Acetabularia mediterranea and A. cliftonii), the rbcS cDNA sequences of B. oerstedii display the codons TAA or TAG, which seem to code for glutamine, in the reading frame. The amino acid substitution rate for the SSU protein was calculated to be 0.35-0.41 amino acids per 10(9) years per site based on the substitutions observed in the SSU amino acid sequences of Acetabularia and Batophora. PMID- 1934114 TI - Structural similarities between psbA genes from red and brown algae. AB - The single copy psbA genes from the multicellular red alga Antithamnion spec. and the brown alga Ectocarpus siliculosus have been cloned and sequenced and monocistronic transcripts have been detected. Both genes contain an insertion of 21 bp at the 3' end which was also found in cyanobacteria and which is absent in chloroplasts and the chlorophyll b-containing prochlorophyte Prochlorothrix hollandica. These findings are in agreement with the hypothesis of a polyphyletic origin of plastids. Plastids of red and brown algae appear to be closely related. PMID- 1934116 TI - Molecular cloning and characterization of a Candida tsukubaensis alpha glucosidase gene in the yeast Saccharomyces cerevisiae. AB - The molecular cloning of an alpha-glucosidase gene isolated from a Candida tsukubaensis (CBS 6389) genomic library in Saccharomyces cervisiae is reported. The cloned gene is contained within a 6.2 kb Sau3A DNA fragment and directs the synthesis and secretion of an amylolytic enzyme into the extracellular medium of the recombinant host, S. cerevisiae. The cloned enzyme was found to have an unusually broad substrate specificity and is capable of hydrolysing alpha-1,2, alpha-1,3, alpha-1,4 and alpha-1,6 linked, as well as aryl and alkyl, D glucosides. On the basis of its substrate specificity profile, the cloned enzyme was classified as an alpha-glucosidase (E.C. 3.2.1.20). It has a pH optimum in the range 4.2-4.6, a temperature optimum of 58 degrees C and is readily inactivated at pasteurization temperature (60 degrees C). Southern blot analysis failed to reveal any homology between the cloned gene and genomic DNA isolated from other well characterized amylolytic yeasts. A rapid plate-assay, based on the utilization of a chromogenic substrate X-alpha-D-glucoside to detect the expression of the cloned alpha-glucosidase in S. cerevisiae transformants, was developed. PMID- 1934115 TI - Repair of gamma ray-induced S1 nuclease hypersensitive sites in yeast depends on homologous mitotic recombination and a RAD18-dependent function. AB - Repair under non-growth conditions of DNA double-strand breaks (DSB) and chromatin sites sensitive to S1 endonuclease (SSS) induced by 60Cobalt-gamma rays were monitored in repair-competent and deficient strains of Saccharomyces cerevisiae by pulsed field gel-electrophoresis. In stationary-phase cells of a repair-competent RAD diploid, and an excision-deficient rad3-2 diploid, SSS are repaired as efficiently as DSB, whereas in a repair-competent RAD haploid, and a rad 50-1 diploid, neither SSS nor DSB are repaired. The rad18-2 diploid repairs DSB well but is defective in SSS repair. Obviously, SSS repair in yeast chromatin, like DSB repair, depends on recombination, but unlike DSB repair depends additionally on RAD18 function. PMID- 1934117 TI - Construction of a Saccharomyces cerevisiae strain able to ferment cellobiose. AB - The bglA gene, encoding a beta-glucosidase from Bacillus polymyxa, has been expressed in Saccharomyces cerevisiae under control of the CYC-GAL promoter inducible by galactose. The expression of bglA-encoded activity in the strain used as a host was not sufficient to allow its growth with cellobiose as a carbon source. However, a recessive mutation in a gene designated cem1 has been obtained which, combined with the expression of beta-glucosidase activity, allows the growth of S. cerevisiae on cellobiose. The expression of the blgA gene in a cem1 strain confers on S. cerevisiae the capability for an efficient fermentation of cellobiose, as detected by the formation of CO2. PMID- 1934118 TI - Uptake of thiamine by Schizosaccharomyces pombe and its effect as a transcriptional regulator of thiamine-sensitive genes. AB - Wild-type fission yeast, growing in minimal medium, actively synthesizes thiamine and maintains an internal concentration which we have measured to be around 10 pmoles/10(7) cells. If thiamine is added to such cultures it is rapidly sequestered by the cell, and if added in excess (20 microM) the internal concentration of thiamine rises almost 1000-fold to a maximum of around 9000 pmoles/10(7) cells before the transport mechanism is shut down. The kinetics of decay of intracellular thiamine to the basal level are consistent with simple dilution as the cell mass doubles. In parallel with this analysis, we have studied the transcriptional activity of the thiamine-sensitive gene nmt1 as a function of intracellular thiamine concentration. Transcription of this gene is rapidly repressed as the internal thiamine concentration rises and is only reactivated as the concentration falls to below about 50 pmoles/10(7) cells. PMID- 1934119 TI - Sterile UGA nonsense mutants of fission yeast. AB - Eight sterile mutants, which regain their fertility upon reactivation of an inactivated UGA suppressor allele of the serine tRNA gene sup3, are shown to carry UGA nonsense alleles of two established ste genes, ste1 (one mutant) and ste6 (two mutants), and of two novel genes, ste9 (four mutants) and ste10 (one leaky mutant of ras1-/ste5-like cell morphology). The mutant alleles of ste1 and ste9 lead to a defect in both conjugation and meiosis, whereas those of ste6 and ste10 affect mating only. Two of the four genes map to chromosome I, ste1 in the left arm 6 cM distal of ura1, and ste9 in the right arm 3 cM distal of ade2. The ste10 and ste6 genes are located in the right arms of chromosomes II and III, respectively, the former 4 cM distal of trp1 and the latter 1 cM proximal or distal of trp3. PMID- 1934120 TI - Characterization of a partially fertile ras1-like ste10-UGA nonsense mutant of fission yeast. AB - Mutants which carry a leaky UGA nonsense mutation in the fertility gene ste10 are characterized by a deformed cell morphology which resembles that described in the literature for sterile ras1- (ste5) and ral1 to ral4 mutant cells. Although frequent conjugation attempts are observed in combinations of two ste10 mutant strains of opposite heterothallic mating type, zygotes and asci are formed only rarely and the fertility of such crosses remains low (not more than 1% of the fertility of comparable crosses of two ste+ wild-type strains). The fertility is considerably increased, however, in combinations of the ste10 mutant with ste+ wild-type strains (up to 10% if the h- partner, and more than 30% if the h+ partner, carries the ste10 mutation. PMID- 1934121 TI - Pheromone production and response in sterile mutants of fission yeast. AB - Genetically heterothallic strains of various sterile mutants were assayed for residual production of the corresponding mating pheromone as well as responsiveness towards the opposite pheromone. No sexual activities were detected in ste11 strains (previously referred to as aff1 or steX, which we show are allelic), whilst the production of M factor was unaffected by ste1 to ste10 mutations. P factor production was still possible in class I ste mutants (ste5, ste6 and ste10), which also allow meiosis in diploid strains. With the exception of the leaky ste10-F23 mutant, no changes in cell morphology were induced by exposure to the opposite pheromone in the ste mutant strains. PMID- 1934122 TI - The yeast rRNA gene enhancer does not function by recycling RNA polymerase I and cannot act as a UAS. AB - The mechanism of action of the yeast rRNA gene enhancer was investigated by measuring transcription of an rRNA minigene, cloned into a multicopy plasmid, in transformed yeast. Expression of the minigene was increased when the enhancer was cloned either upstream of or downstream from the minigene. When an enhancer was present both upstream and downstream of the minigene, the upstream element was functionally dominant. The upstream enhancer was active in this construct in the absence of detectable read-through by any RNA polymerase. In a construct containing tandem rRNA minigenes, an enhancer element located between the two promoters activated transcription from both independently. Therefore, the enhancer does not appear to activate transcription by recycling RNA polymerase I molecules to the promoter. The enhancer also failed to activate transcription from the intact promoter of the yeast CYC1 gene, and was unable to functionally substitute for the natural upstream activation sequences (UASs) of this gene. Therefore, the enhancer functions differently to UASs of RNA polymerase II genes, and is probably polymerase-specific. PMID- 1934123 TI - Characterization of circular mitochondrial plasmids in three Pythium species. AB - Four circular plasmids, with a monomer size ranging from 3.2 to 4.94 kb, have been identified in isolates of P. aphanidermatum (two different plasmids), P. torulosum, and an unidentified echinulate isolate. The mitochondrial location has been confirmed for three of the plasmids. Each fungal isolate contained a single plasmid, present in both monomeric and oligomeric forms; plasmid monomers were present as open circles and as supercoiled forms. Restriction maps of the plasmids were dissimilar. Hybridization studies using cloned plasmids revealed no DNA sequence similarity among the different plasmids or between the plasmids and the nuclear or mitochondrial genome of the isolates from which they were recovered. Hybridization of labeled plasmid DNA to Northern transfers of mitochondrial RNA for two isolates indicate that what appears to be the predominant RNA transcript is unit length in size. For three isolates, the plasmid was retained following subculturing and was present in all asexual and sexual single-spore progeny evaluated. For one isolate of P. aphanidermatum the plasmid was unstable and was lost during subculturing. PMID- 1934124 TI - A genetic analysis of an alpha-amylase super-secretor in yeast; implications for the regulatory pathway. AB - Extracellular glucoamylase activity was increased by a gene, which is present in super-secretor, but absent in low-secretor, strains of the yeast Saccharomyces cerevisiae. Genetic data indicated that this super-secretor gene is linked to the STA3 structural gene for glucoamylase. This gene appears to act specifically since it increased the secretion of glucoamylase but not of other secreted enzymes like acid phosphatase and invertase. PMID- 1934125 TI - Polymorphism within the nuclear and 2 micron genomes of Saccharomyces cerevisiae. AB - Seven strains of bakers' yeast were obtained as a representative sample of the Spanish baking industry. The nuclear genome was monitored for polymorphism by transverse alternating field electrophoresis (TAFE) and restriction maps of 2 micron DNA were produced. All seven strains were uniquely different when evaluated by their total chromosomal lengths whereas only two 2 micron variants were defined. There was no apparent correlation between chromosomal and plasmid polymorphism. The extensive chromosomal polymorphism within one 2 micron DNA type indicates the rapid and relatively recent evolution of the nuclear genome. The hybrid origin (S. cerevisiae-S. monacensis) of lager yeast was critically evaluated by TAFE analysis of S. cerevisiae and S. carlsbergensis chromosomes. The absence of corresponding S. cerevisiae chromosomes III and XIII in S. carlsbergensis argued against the hybrid origin of lager strains. We discuss limitations of the hybrid origin hypothesis of industrial yeasts and propose that the molecular coevolution observed in 2 micron DNA serves as a useful additional mechanism for rationalization of some of the structural polymorphism of the nuclear genome. PMID- 1934126 TI - Common genes and pathways in the regulation of the mitotic and meiotic cell cycles of Schizosaccharomyces pombe. AB - Cell division cycle mutants defective in G1, DNA replication or nuclear division were tested for sporulation at semi-restrictive temperatures. In cdc1-7, cdc5 120, cdc17-L16 and cdc18-46 no abnormalities were observed; cdc10-129, cdc20-M10, cdc21-M6B, cdc23-M36 and cdc24-M38 formed four-spored asci but with a low efficiency; cdc22-M45 was completely defective in meiosis, but could conjugate and formed zygotes with a single nucleus. Mutants defective in the mitotic initiation genes cdc2, cdc25 and cdc13 were blocked in meiosis II. None of the wee1-50, adh.nim1+ and win1+ alleles had any affect on sporulation, suggesting that their interactions with cdc25 and cdc2 are specific to mitosis. The meiotic function of cdc13 is TBZ-sensitive and probably exerted downstream of cdc2. Single mutants in cut1 or cut2 did not effect sporulation, whereas the double mutant cut1 cut2 formed two-spored asci. The results demonstrate that the cell division cycle and the meiotic developmental pathway share common genes and regulatory cascades. PMID- 1934127 TI - Hygromycin- and paromomycin-resistant mutants of Aspergillus nidulans alter translational fidelity. AB - Mutants of Aspergillus nidulans resistant to the aminoglycoside antibiotics paromomycin and hygromycin B have been isolated and their growth characteristics are described here. Most paromomycin mutants were cross-resistant to hygromycin and geneticin. All the hygromycin-resistant mutants were slightly cross-resistant to geneticin. Out of the 15 mutants tested 14 had drug-resistant ribosomes in vitro and all 12 of those investigated further had reduced levels of translational misreading. Five new loci have been found--parA on linkage group I, hygA on III, hygB on IV, hygC on V, hygD on VI and parB on VIII. This increases, to at least 12, the number of translational fidelity loci in A. nidulans. PMID- 1934128 TI - Cloning, sequencing and expression of the Schwanniomyces occidentalis NADP dependent glutamate dehydrogenase gene. AB - The cloned NADP-specific glutamate dehydrogenase (GDH) genes of Aspergillus nidulans (gdhA) and Neurospora crassa (am) have been shown to hybridize under reduced stringency conditions to genomic sequences of the yeast Schwanniomyces occidentalis. Using 5' and 3' gene-specific probes, a unique 5.1 kb BclI restriction fragment that encompasses the entire Schwanniomyces sequence has been identified. A recombinant clone bearing the unique BclI fragment has been isolated from a pool of enriched clones in the yeast/E. coli shuttle vector pWH5 by colony hybridization. The identity of the plasmid clone was confirmed by functional complementation of the Saccharomyces cerevisiae gdh-1 mutation. The nucleotide sequence of the Schw. occidentalis GDH gene, which consists of 1380 nucleotides in a continuous reading frame of 459 amino acids, has been determined. The predicted amino acid sequence shows considerable homology with GDH proteins from other fungi and significant homology with all other available GDH sequences. PMID- 1934130 TI - The fate of mitochondrial DNAs of mt+ and mt- origin in gametes and zygotes of Chlamydomonas. AB - In order to study the mechanism responsible for the uniparental transmission of the mitochondrial genome in crosses between Chlamydomonas reinhardtii and C. smithii, we have analyzed the fate of mitochondrial DNA during gametogenesis, zygospore differentiation and sporulation by hybridization experiments. Both mt+ and mt- gametes contain the same amount of mitochondrial DNA and the two parental genomes persist for several days in the zygotes. The DNA of mt+ origin is slowly eliminated during the period of zygote maturation. Light is required for total elimination of mt+ mitochondrial DNA in the zygospores. Using appropriate restriction enzymes, we have been unable to detect methylation of the mitochondrial DNA during gametogenesis or zygospore formation. The possibility that the mt+ mitochondria themselves are specifically eliminated in the course of zygote maturation is discussed. PMID- 1934131 TI - Evidence for the presence of hairpin chloroplast DNA molecules in barley cultivars. AB - Total DNA was extracted from young green and etiolated barley leaf shoots and run on 2D neutral/alkaline agarose gels. This technique showed the presence of molecules which behaved as though their single-stranded length was twice their double-stranded length. This behaviour was sensitive to S1 nuclease. Our conclusion is that these DNAs are hairpin molecules. They are homologous to sequences found throughout the barley chloroplast genome. This type of molecule is present in uncut DNA with a continuous range of sizes varying between 0.5 and 15 kbp in our experimental conditions. The origin and possible biological function of these molecules is discussed. PMID- 1934129 TI - The kalilo linear senescence-inducing plasmid of Neurospora is an invertron and encodes DNA and RNA polymerases. AB - The nucleotide sequence of kalilo, a linear plasmid that induces senescence in Neurospora by integrating into the mitochondrial chromosome, reveals structural and genetic features germane to the unique properties of this element. Prominent features include: (1) very long perfect terminal inverted repeats of nucleotide sequences which are devoid of obvious genetic functions, but are unusually GC rich near both ends of the linear DNA; (2) small imperfect palindromes that are situated at the termini of the plasmid and are cognate with the active sites for plasmid integration into mtDNA; (3) two large, non-overlapping open-reading frames, ORF-1 and ORF-2, which are located on opposite strands of the plasmid and potentially encode RNA and DNA polymerases, respectively, and (4) a set of imperfect palindromes that coincide with similar structures that have been detected at more or less identical locations in the nucleotide sequences of other linear mitochondrial plasmids. The nucleotide sequence does not reveal a distinct gene that codes for the protein that is attached to the ends of the plasmid. However, a 335-amino acid, cryptic, N-terminal domain of the putative DNA polymerase might function as the terminal protein. Although the plasmid has been co-purified with nuclei and mitochondria, its nucleotide composition and codon usage indicate that it is a mitochondrial genetic element. PMID- 1934132 TI - Mapping of four ras superfamily genes by physical and genetic means in Schizosaccharomyces pombe. AB - Four ras superfamily genes, namely ypt1, ypt2, ypt3 and ryh1, have been located on the S. pombe linkage map. This was achieved by constructing strains carrying a new NotI cutting site and the S. cerevisiae LEU2 gene integrated next to the respective gene. The physical location of these genes of the chromosomes was then determined by NotI restriction analysis of the DNA prepared from each strain. Fine genetic mapping was carried out by conventional tetrad analysis using the integrated LEU2 gene as a marker. The results indicated that ypt1 is tightly linked to top1 on the right arm of chromosome II; that ypt2 is 2.5 cM apart from ura2 on the right arm of chromosome I; that ypt3 is tightly linked to arg3 on the left arm of chromosome I; and that rhy1 is located approximately 20 cM from ade3 on the left arm of chromosome I. PMID- 1934133 TI - Electrophoretic karyotype of cellulolytic Penicillium janthinellum strains. AB - The genome of the cellulolytic fungus Penicillium janthinellum BIOURGE was resolved completely by rotating field electrophoresis. The gel pattern revealed 8 10 different chromosomes. On the basis of data for yeast chromosome size standards from Schizosaccharomyces pombe and Saccharomyces cerevisiae, chromosome sizes in the range from 2.0 to 8 mb were estimated. By Southern hybridization with heterologous probes, the chromosomal locations of rDNA, the elongation factor EF1, actin and ubiquitin have all been mapped. In addition, first results with heterologous and homologous probes for cellulolytic genes from Trichoderma reesei and P. janthinellum are presented. In contrast to the other probes, signals obtained with cellulase genes are clearly distributed over several chromosomes. PMID- 1934134 TI - Structure of the Aspergillus niger pelA gene and its expression in Aspergillus niger and Aspergillus nidulans. AB - Aspergillus niger pectin lyases are encoded by a multigene family. The complete nucleotide sequence of the pectin lyase PLA-encoding gene pelA has been determined. Comparison of the deduced amino acid sequence with the deduced amino acid sequence of the other characterized pectin lyase, PLD, shows that the proteins share 69% amino acid identity. When grown on media with pectin as the sole carbon source, A. niger transformants containing multiple copies of the pelA gene show raised mRNA levels and overexpression of the gene product PLA compared with the wild-type strain. PLA was purified and characterized. In A. nidulans transformants PLA is also produced in medium containing a high concentration of glucose and no pectin. PMID- 1934136 TI - High efficiency transformation of Tolypocladium geodes conidiospores to phleomycin resistance. AB - A convenient and efficient transformation system has been developed for the filamentous fungus Tolypocladium geodes. In contrast to most of the commonly described techniques requiring prior preparation of protoplasts or spheroplasts, this method leads to high efficiency transformation of T. geodes conidiospores following moderate lytic enzyme treatment. Competent cells so obtained are still resistant to osmotic pressure and can be stored frozen without loss of viability. The highest transformation frequency (3-5 x 10(3) transformants per microgram of DNA) was obtained with plasmid pUT737 containing the Sh ble gene conferring phleomycin resistance under the control of a strong promoter isolated from Trichoderma reesei. Southern hybridization revealed multiple integration sites of plasmid DNA into the T. geodes nuclear DNA despite the absence of homology between the transforming DNA and the recipient genome. Instability could not be detected for the phleomycin phenotype during more than five generations of mitotic growth under non-selective conditions. PMID- 1934137 TI - Plastid genome structure and plastid-related transcript levels in albino barley plants derived from another culture. AB - Southern analysis of DNA from four albino barley plants regenerated from microspores by direct embryogenesis revealed the presence of plastid genomes which had undergone deletion or alteration of specific restriction fragments (delta ptDNAs). In contrast, a fifth plant appeared to contain an intact plastid genome. All the albino plants studied contained reduced amounts of ptDNA, the most abundant restriction fragments being present at levels between 6% and 20% of those found in the leaves of green seedlings. Steady-state levels of transcripts from plastid and nuclear genes encoding plastid components were estimated by Northern analysis of RNA from albino plants. Transcripts from the plastid genes rbcL, psbD-psbC and the 16S and 23S rRNAs were undetectable or were present at greatly reduced levels in albino plants compared to those found in green leaves. Transcripts from the nuclear genes rbcS and cab, which encode chloroplast localised proteins, were also present at reduced levels in albino pollen plants. Levels of the nuclear encoded 25S rRNA, which is not a plastid component, were found to be identical in albino plants and green leaves suggesting that only the expression of plastid-related genes may be affected in albino plants. The general reduction of plastid-related transcripts was independent of the different patterns of ptDNA alteration seen in albino pollen plants. PMID- 1934135 TI - Identification and characterization of a second polygalacturonase gene of Aspergillus niger. AB - The filamentous fungus Aspergillus niger produces several endopolygalacturonases that are involved in the degradation of pectin. PGI, the enzyme representing the second most abundant activity in a commercial enzyme preparation, was further characterized and the corresponding gene was isolated. The nucleotide sequence of the pgaI gene was determined and the protein coding region was found to be interrupted by two short introns, one of which has a unusual donor splice site. The deduced 368 amino acids long protein with a putative prepropeptide of 31 amino acids shows 60% sequence identity to PGII in the mature protein. PGI overproducing A. niger strains were obtained by cotransformation with the cloned gene. PMID- 1934138 TI - Manitoba HIV seroprevalence study. PMID- 1934139 TI - Salmonella poona. PMID- 1934140 TI - Measles--United States, 1990. PMID- 1934141 TI - Invasive streptococcal disease--Prince Edward Island. PMID- 1934142 TI - Severe group A streptococcal disease--southern Ontario. Ontario Streptococcal Study Group. PMID- 1934143 TI - European tick-borne encephalitis. PMID- 1934144 TI - Tropical health and quarantine notes. PMID- 1934145 TI - Butylated hydroxyanisole in perspective. AB - Butylated hydroxyanisole (BHA) is a synthetic food antioxidant used to prevent oils, fats and shortenings from oxidative deterioration and rancidity. This review depicts the current knowledge on BHA. The physical and chemical characteristics of BHA are summarized and its function as a food antioxidant is made clear. The toxicological characteristics of BHA and its metabolic fate in man and animal are briefly reviewed. Special emphasis is laid on the carcinogenicity of BHA in the forestomach of rodents and to related events in the forestomach and other tissues in experimental animals. At present there is sufficient evidence for carcinogenicity of BHA, but there is hardly any indication that BHA is genotoxic. Therefore risk assessment for this epigenetic carcinogen is based on non-stochastic principles. However, the mechanism underlying the tumorigenicity of BHA is not known. In the last part of this review an attempt is made to unravel the unknown mechanism of carcinogenicity. It is hypothesized that BHA gives rise to tumor formation in rodent forestomach by inducing heritable changes in DNA. Evidence is being provided that reactive oxygen species, in particular hydroxylradicals, may play a crucial role. The key question with respect to risk assessment for BHA is whether or not the underlying mechanism is thresholded, which is important for the choice of the appropriate model to assess the risk, if any, for man and to manage any potential risk. PMID- 1934147 TI - Effects of superoxide dismutase on the autoxidation of 1,4-hydroquinone. AB - During autoxidation of 1,4-hydroquinone (H2Q, less than 1 mM) at pH 7.4 and 37 degrees C, stoichiometric amounts of 1,4-benzoquinone (Q) and hydrogen peroxide were formed during the initial reaction. The reaction kinetics showed a significant induction period which was abolished by minute amounts of Q. Hydrogen peroxide and catalase were without effect on the autoxidation process. Transition metals apparently were not involved, since chelators like EDTA, DETAPAC, and desferrioxamine or FeSO4 had no influence on the autoxidation kinetics. Superoxide dismutase (SOD) did not abolish the induction period but dramatically enhanced the autoxidation rate by more than two orders of magnitude. The stimulatory effect was first-order in SOD concentration but showed saturation kinetics. The dependence of Q and hydrogen peroxide formation rates on H2Q concentration shows a biphasic behaviour: dependence on the square at low H2Q, but on the square root at high H2Q concentration. As revealed by calculatory simulations the results can be adequately described by the known reaction rate constants. The reaction starts with the comproportionation of H2Q and Q to yield two semiquinone molecules which autoxidize to give two superoxide radicals and two molecules of Q which enter into a new cycle of comproportionation. Because of unfavourable equilibria the autocatalytic reaction soon comes to steady state, and the further reaction is governed by the rate of superoxide removal. At excess SOD, the comproportionation reaction is rate-limiting, thus explaining the saturation effects of SOD. The experiments do not allow a decision between the two functions of SOD; the conventional action as a superoxide:superoxide oxidoreductase or as a semiquinone:superoxide oxidoreductase. In the latter reaction SOD is thought to be reduced by semiquinone with Q formation. In the second step the reduced enzyme would be re-oxidized by a superoxide radical which is formed during autoxidation of the second semiquinone molecule generated in the comproportionation reaction. From thermodynamic considerations, the latter function of SOD appears to be plausible. PMID- 1934146 TI - A nuclear factor that interacts with metal responsive elements of a human metallothionein gene. AB - Metallothioneins (MTs) are low molecular weight heavy metal-binding proteins which are known to play a major role in heavy metal detoxification and understanding of their regulatory mechanism is toxicologically important. Expression of MT genes is induced by heavy metals and metal responsive elements (MREs) upstream of MT genes are essential for the transcriptional activation. By several types of mobility shift assay with 32P-labeled oligonucleotide probes, we detected HeLa cell nuclear as well as cytoplasmic factors that bind to MRE sequences of human MTIIA (hMTIIA) gene. One of the nuclear factors, which gives stronger signal than others, was further characterized. Competition experiments showed that the nuclear factor (named MREBP) specifically recognizes MREs of hMTIIA gene. EDTA abolished the binding of MREBP to MRE, suggesting that a divalent cation(s) is required for the complex formation. Also in blotting experiments with HeLa nuclear extract and the [32P]MRE probes an EDTA-sensitive 95k protein band, which possibly represents MREBP, was detected. PMID- 1934148 TI - Relationship between mutagenicity and DNA adduct formation in mammalian cells for fjord- and bay-region diol-epoxides of polycyclic aromatic hydrocarbons. AB - Chinese hamster V79 cells were treated with the anti- and syn-diastereomers of the bay- or fjord-region diol-epoxides of four polycyclic aromatic hydrocarbons, namely benzo[a]pyrene (BP), benzo[c]chrysene (BcC), benzo[g]chrysene (BgC) and benzo[c]phenanthrene (BcPh). The frequency of induction of 6-thioguanine resistant mutations was determined, and the extent of formation of DNA adducts was measured by 32P-postlabelling. When expressed as mutation frequency per nanomoles compound per millilitre incubation medium, this group of chemicals expressed a 160-fold range in potency. In agreement with previous experimental studies, the anti-diol-epoxide of BcC was highly mutagenic, inducing in excess of 3 x 10(4) mutations/10(6) cells per nmol compound/ml. The mutagenic activities of the anti- and syn-diol-epoxides of BP were 10- and 100-fold lower, respectively. Both diol-epoxides of BgC, the syn-BcC and the anti-BcPh derivatives were also highly mutagenic, and only the syn-BcPh diol-epoxide was less mutagenic than the anti-diol-epoxide of BP. Determination of the levels of DNA adducts formed by the diol-epoxides indicated that the most mutagenic compounds were the most DNA reactive, although the fjord-region diol-epoxides gave rise to more complex patterns of adducts than those of the BP diol-epoxides. When the mutagenicity results were expressed as mutations per femtomoles total adducts formed, all compounds showed similar activities. Thus the potent mutagenicity of the fjord region diol-epoxides appears to be due to the high frequency with which they form DNA adducts in V79 cells, rather than to formation of adducts with greater mutagenic potential. PMID- 1934149 TI - Investigation of the chemical basis of nitroalkane toxicity: tautomerism and decomposition of propane 1- and 2-nitronate under physiological conditions. AB - Unlike primary nitroalkanes, such as 1-nitropropane, the secondary nitroalkane 2 nitropropane is geno- and hepatotoxic. Nitroalkanes exist in equilibrium with alkane nitronates. In order to investigate the relationship between nitroalkane toxicity and generation and stability of nitronates, propane 1- or 2-nitronate (4 6 mM) were incubated in buffer (pH 3.8 -7.4) in the absence or presence of cysteine. Equilibrium formation and degradation were studied by 1H-NMR spectroscopy and ion pair HPLC chromatography. Propane 1-nitronate generated 1 nitropropane rapidly and almost quantitatively. In the case of propane 2 nitronate equilibrium at pH 7.4 was reached within 8 h, when 48% of initial nitronate had tautomerised to 2-nitropropane. The pKa of the reaction 2 nitropropane less than--greater than propane 2-nitronate measured by HPLC was 7.63. Equilibrium formation, hydrolysis and reduction of nitronates were pH dependent and, in the case of propane 2-nitronate, yielded mainly acetone, nitrite and acetone oxime, apart from 2-nitropropane. Hydrolysis of propane 2 nitronate (4 mM) to nitrite was modulated by cysteine (4 mM) and p-methoxyphenol (0.4 mM). At pH 7.4 they increased nitrite generation by 300 and 28%, respectively, at pH 4.8 they decreased nitrite formation by 91 and 82%, respectively, probably by scavenging radical intermediates. Differences between nitroalkanes in terms of content of nitronate tautomer at equilibrium are probably an important chemical determinant of their toxic potential. PMID- 1934150 TI - Effects of strychnopentamine on cells cultured in vitro. AB - This paper describes the powerful cytotoxic action exerted by strychnopentamine (SP), a dimeric indole alkaloid extracted from Strychnos usambarensis Gilg, on B16 melanoma cells and on non-cancer human fibroblasts cultured in vitro. SP strongly inhibits cell proliferation and induces cell death at a relatively low concentration (less than 1 microgram/ml) after 72 h of treatment in the two lines. Incorporation of [3H]thymidine and [3H]leucine by B16 cells significantly decreases after only 1 h of treatment at 0.5 microgram/ml. SP induces the formation of dense lamellar bodies and vacuolization in the cytoplasm, intense blebbing at the cell surface and various cytological alterations leading to cell death. PMID- 1934151 TI - Cytoskeleton as a target in menadione-induced oxidative stress in cultured mammalian cells: alterations underlying surface bleb formation. AB - Several in vitro and in vivo studies have suggested that surface bleb formation during oxidative cell injury is related to alteration in cytoskeleton organization. Various cell lines different in origin and growth characteristics were exposed to 2-methyl-1,4-naphthoquinone (menadione) which is known to induce bleb formation and cytotoxicity by generating considerable amounts of oxygen reactive species. Treated cells were analyzed by means of immunocytochemistry and electron microscopy in order to investigate the morphological and molecular features underlying bleb generation. The results obtained indicate that menadione induced bleb formation is a widely observed phenomenon present mainly in round or mitotic cells. Surface blebs appear free of organelles and contain only few ribosomes and amorphous material. Occasionally, they undergo detachment from the cell surface as large cytoplasmic vesicles. Bleb surfaces with protein clusters as well as bald blisters with an almost exclusive localization of intramembrane particles on their narrow base were detected using freeze-fracture techniques. Immunocytochemical investigations performed on menadione-exposed cells revealed that some surface proteins (collagen IV, sialo-proteins, beta 2 microglobulin and fibronectin) and adhesion molecules (vinculin) underwent changes in their expression over the bleb surface. Moreover, different behavioural characteristics of actin microfilaments, vimentin and keratin intermediate filaments and microtubules was observed. Alpha-actinin, vimentin and microtubular proteins (tubulin, MAPs and tau) were detected within the blebs. On the other hand, actin and keratin filaments appeared to be absent. The results presented here demonstrate that cytoskeletal structures and the microfilament system in particular, represent important targets in menadione-induced morphological changes in cultured cells. These changes appear to lead to the redistribution of several cytoskeletal and membrane proteins as well as dissociation of the cytoskeleton network from its anchoring domains in the plasma membrane thus generating sites of structural weakness where blebs would arise and progressively grow. Experimental evidence supporting a crucial role of thiol oxidation and elevation of cytoplasmic calcium concentration in bleb formation is also provided. PMID- 1934152 TI - Cytogenetic effect of thioridazine hydrochloride in mice and in human lymphocyte chromosomes. AB - Thioridazine hydrochloride, a drug of the phenothiazine group with a piperidine side chain is widely used in human medicine as a psycho-relaxant and anxiolytic agent. The mutagenic effects of thioridazine hydrochloride were studied in Swiss albino mice. The animals were treated with 4, 6 and 8 mg/kg of thioridazine hydrochloride for the micronucleus test, analysis of chromosomes in germ cells, and for sperm morphology assay. Human lymphocyte cultures were treated in vitro with 0.75, 1.25 and 1.75 mg/culture of thioridazine hydrochloride for 24, 48 and 72 hours. The study showed no significant increase in the frequency of micronuclei, chromosomal aberrations in germ cells and sperm head abnormalities in mice, or chromosomal aberrations in human lymphocyte cultures. PMID- 1934153 TI - Management of mild or moderate hypertension is simple. PMID- 1934154 TI - Rate-pressure product and arterial oxygen saturation during electroconvulsive therapy. AB - The arterial oxygen saturation, heart rate and systolic blood pressure were measured in 100 patients undergoing electroconvulsive therapy under general anaesthesia. All patients were anaesthetised using thiopentone and suxamethonium. In spite of ventilation with oxygen during the procedure a marked degree of hypoxaemia occurred during the convulsion in 80% of the patients. This was associated with a highly significant rise in heart rate and blood pressure (p less than 0.001). During electroconvulsive therapy there is an imbalance between myocardial oxygen supply and consumption. PMID- 1934155 TI - Myiasis due to Cardylobia anthropophaga, the 'Tumbu fly' in a Sri Lankan infant. AB - A case of myiasis due to Cardylobia anthropophaga (Blanchard) (Diptera: Calliphoridae), the 'Tumbu fly', is reported for the first time in Sri Lanka, in a 10 month old infant. The infection was acquired in Zimbabwe. The child had appeared 'unwell' for nearly a week before the detection of the skin lesions. The main clinical features were irritability, restlessness and the appearance of three small lumps on the scalp behind the right ear. Identification of the fly larva and the management of myiasis are discussed. PMID- 1934157 TI - The polycystic ovary syndrome. PMID- 1934156 TI - A glimpse into the history of Arabian medicine. PMID- 1934158 TI - Place of immunohistochemistry in renal pathology. PMID- 1934159 TI - Growth hormone deficiency in Sri Lanka: a preliminary study. AB - Growth hormone deficiency is a recognised cause of severe short stature. A community of 16,001 Sri Lankan children aged between 5 and 6 years was screened for short stature using a simple growth chart, and a sample of 172 identified as short was investigated for the aetiology. Growth hormone deficiency was confirmed in 12 out of the 172 children using the insulin-induced hypoglycaemia test. Another group of 27 out of the 172 children who could potentially benefit from growth hormone therapy were identified using an exercise screening test. Growth hormone deficiency has not been previously documented in Sri Lanka. PMID- 1934160 TI - Lipid patterns and fibrinogen levels of smokers and non-smokers. AB - Hypercholesterolaemia, smoking and elevated levels of fibrinogen are independent risk factors for cardiovascular disease (CVD). The aim of this study was to determine whether smoking indirectly affects the other risk factors, namely cholesterol and fibrinogen levels. Serum lipid patterns and fibrinogen levels were determined in 67 cigarette or beedi smokers and 51 non-smokers in the age group 18 to 50 years. Serum thiocyanate levels were measured as an indirect indicator or smoking exposure. Smokers had significantly higher serum thiocyanate levels than non-smokers. The serum total cholesterol levels in smokers was significantly higher than in non-smokers, but there was no association with the degree of smoking. In contrast, smokers had significantly elevated fibrinogen levels which were positively related to thiocyanate levels, indicating that plasma fibrinogen levels increase in smoking exposure. These results suggest that smoking may increase the risk of CVD by elevating plasma fibrinogen levels. PMID- 1934161 TI - Pharmacological activities of the prenylcoumarins, developed from folk usage as a medicine of Peucedanum japonicum THUNB. AB - In connection with the chemical structure of coumarin 1 (a mixture of acetylangeloylkhellactone and acetyltigloylkhellactone), a compound isolated from Peucedanum japonicum THUNB., we synthesized eight coumarin compounds (3-10) and performed pharmacological studies on these nine compounds, as well as on another coumarin, praeruptorin A (= Pd-Ia) (2), a compound isolated from Peucedanum praeruptorum DUNN. We studied the effects of compounds 1-5 on isolated smooth muscle and of compounds 1-10 on the cardiovascular system. These compounds showed dose-related antagonistic effects on histamine- and Ca(2+)-induced contractions in smooth muscle and the potencies were in the order 2 greater than 1 greater than seselin (3) greater than xanthyletin (4) = 2.2.10-trimethyl-2H,8H-benzo[1,2 b: 3,4-b']dipyran-8-one (5). All the compounds except 7-geranyloxy-4 methylcoumarin (10) produced a dose-related increase in vertebral, carotid and femoral blood flow. Compounds 1, 5, and 4-methyl-7-(3-methyl-2 butenyloxy)coumarin (8) caused an increase in blood pressure, but 3 and 4 caused a slight decrease. Compounds 2, 3, 4, 5, and 8 increased heart rate. Jatamansinone (6) and jatamansinol (7) caused only slight changes in blood pressure. All the compounds except 10 increased heart rate. Compound 1 also increased blood flow in the cerebral cortex. Thus, compound 1 was confirmed to have an inhibitory effect on contraction in isolated smooth muscle and an action increasing arterial blood flow. Among the compounds tested in this study, 3, as well as 6 and 7 synthesized on the basis of 3, showed actions similar to those of Ca2+ blockers and some compounds had papaverine-like activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934162 TI - 2-Oxo-1,3-dioxoles as specific substrates for measurement of arylesterase activity. AB - Various 4-arylthiomethyl-2-oxo-1,3-dioxole derivatives IIIa-o were synthesized. Their hydrolysis rates by arylesterase (EC 3.1.1.2) and cholinesterase (EC 3.1.1.8) in human serum were evaluated. Some of them were not hydrolyzed by cholinesterase, but were hydrolyzed easily by arylesterase. Among the substrates, sodium 4-((5-methyl-2-oxo-1,3-dioxol-4-yl)methylthio)benzenesulfonate (IIIg) was selected for its substrate reactivity toward arylesterase and its good water solubility. In addition, neither aliesterase (EC 3.1.1.1), acetylesterase (EC 3.1.1.6) nor cholesterol esterase (EC 3.1.1.13) hydrolyzed the compound. IIIg is thus concluded to be a specific substrate for arylesterase. Our assay system for serum arylesterase using IIIg can be readily applied to an automatic analyzer in the diagnosis of liver cirrhosis. PMID- 1934163 TI - Antiulcer agents. II. Synthesis and gastric acid antisecretory activity of N-[3 (3-(piperidinomethyl)phenoxy)propyl]-4-(1-methyl-1H- tetrazol-5-ylthio)butanamide and related compounds. AB - N-[3-(3-(Piperidinomethyl)phenoxy)propyl]butanamides having a 1-methyl-1H tetrazol-5-ylthio moiety as a pharmacophore and related compounds were prepared and tested for their antisecretory activity against histamine-induced gastric acid secretion in conscious rats with gastric fistulas. Most of the compounds showed antisecretory activity. Among them, N-[3-(3 (piperidinomethyl)phenoxy)propyl]-4-(1-methyl-1 H-tetrazol-5-ylthio)butanamide (5f) was found to posses the most potent activity, and a possibility of isosteric replacement of the methoxycarbonyl group with 1-methyl-1H-tetrazol-5-yl group was indicated. The structure-activity relationships are also discussed. PMID- 1934164 TI - Studies on antidiabetic agents. X. Synthesis and biological activities of pioglitazone and related compounds. AB - Various analogues of a new antidiabetic agent, pioglitazone (AD-4833, U-72107), were synthesized in order to study in more detail the structure-activity relationships of this class of drug. 5-(4-Pyridylalkylthiobenzyl)-2,4 thiazolidinediones (I), thia-analogues of pioglitazone, were prepared via Meerwein arylation of the alkylthioanilines (IV). 5-(4-Pyridylalkoxybenzylidene) 2,4-thiazolidinediones (IIa) and related heterocyclic analogues (IIb) were synthesized by Knoevenagel condensation of the aldehydes (VIII) with the corresponding azolidinones. Compounds I and II were evaluated for hypoglycemic and hypolipidemic activity in genetically obese and diabetic yellow KK (KKAy) mice. Several 5-[4-[2-(2-pyridyl)ethoxy]-benzylidene]-2,4- thiazolidinediones (IIa) were equipotent to pioglitazone. However, the thia-analogues (I) and the benzylideneheterocycles (IIb) had decreased activity. Catalytic hydrogenation of the 5-benzylidene analogue (14) was found to be a convenient new synthetic method for pioglitazone. The configuration of 14 is also discussed. PMID- 1934165 TI - Synthesis and antitumor activity of 20(S)-camptothecin derivatives: carbamate linked, water-soluble derivatives of 7-ethyl-10-hydroxycamptothecin. AB - Novel 36 derivatives (6), bonding the phenolic hydroxyl group of 7-ethyl-10 hydroxycamptothecin (4) with diamines through a monocarbamate linkage, were synthesized and their antitumor activity was evaluated in vivo. The derivatives were soluble in water as their HCl salts with the E lactone ring intact and exhibited significant antitumor activity. One of the derivatives, 6-27 showed excellent activity against L1210 leukemia and other murine tumors. The structure of its hydrochloride trihydrate (CPT-11) was determined by spectroscopic and crystallographic methods. PMID- 1934166 TI - Relative inhibitory activity of berberine-type alkaloids against 12-O tetradecanoylphorbol-13-acetate-induced inflammation in mice. AB - Forty eight derivatives of berberine-type alkaloids were examined for their inhibition activity against the induction of edema on mouse ear by application of 12-O-tetradecanoylphorbol-13-acetate (TPA). Berberine had an inhibitory effect against TPA-induced ear edema at a grade corresponding to those of quercetin, caffeine and cepharanthine. Berberine derivatives had stronger inhibitory activity than palmatine derivatives. 9-N,N-Diphenylcarbamoyl derivatives of both 9-demethylberberine and 9-demethylpalmatine had rather strong activity. These inhibitory activities are about ten times the activity of the respective mother compounds. Furthermore, 9-N-monophenylcarbamoyl derivatives and N,N diphenylcarbamoyl chloride are found to have no effect. PMID- 1934167 TI - A new enzyme immunoassay for a solid Chinese crude drug, pinellia tuber. AB - A new immunoassay for a solid Chinese crude drug was studied. An antiserum specific for Pinellia tuber was elicited in two rabbits. Using the antiserum and powdered Pinellia tuber-coated microtiter plate as the immunological reagents, and beta-D-galactosidase-labeled goat anti-rabbit immunoglobulin G (IgG) as the tracer, a new enzyme immunoassay for a solid Pinellia tuber with a working range between 0.1 and 1000 micrograms/ml was developed. The assay was specific for a solid Pinellia tuber and showed low cross-reaction values on other Chinese crude drugs and the extract of Pinellia tuber. The specificity of the assay was compared with the selected antibody enzyme immunoassay (SAEIA) for the extract of Pinellia tuber recently developed. Both methods utilized the same immunological reagents such as the serum and the enzyme-labeled goat anti-rabbit IgG, and the only difference between them was the solid-phase antigen used. The assay results of several antigens determined by them were quite different, showing that selective measurements of different antigens, either solid or the extract of Pinellia tuber, were possible using the same antiserum, when the tracing reaction in the immunoassay was adequately selected. PMID- 1934168 TI - New polyphenolic 5'-nucleotidase inhibitors isolated from the wine grape "Koshu" and their biological effects. AB - New 5'-nucleotidase inhibitors designated as NPF-88BU-IA, NPF-88BU-IB, NPF-88BU IIA and NPF-88BU-IIB, respectively, were isolated from the seeds and skin of the wine grape "Koshu". They were purified by solvent extraction, dialysis, and reversed-phase high performance liquid chromatography (HPLC). Their physico chemical properties revealed these compounds to be polyphenolic substances. The average relative molecular masses of the four were estimated by gel permeation chromatography (GPC) analysis to be 7850, 5950, 11900, and 11300, respectively. They strongly inhibited 5'-nucleotidase activities from snake venom and rat liver membrane, and displayed significant therapeutic activity against Ehrlich ascites carcinoma. They also showed inhibitory effects on the growth of Streptococcus mutans MT8148(c), a primary cariogenic bacterium. Furthermore, these 5' nucleotidase inhibitors inhibited the glucan formation from sucrose. These results suggest that the 5'-nucleotidase inhibitors can prevent the cause of caries of tooth. PMID- 1934170 TI - Lipid peroxidation of the erythrocyte membrane caused by stimulated polymorphonuclear leukocytes in the presence of ferritin. AB - Lipid peroxidation of erythrocyte membrane was caused by phorbol myristate acetate (PMA)-stimulated polymorphonuclear leukocytes (PMN) in the presence of ferritin. PMN themselves were not peroxidized. A lag period was observed before the start of the peroxidation reaction. In contrast, ferritin iron was continuously released by PMA-stimulated PMN, suggesting that accumulation of free iron in the reaction system was important for proceeding of the peroxidation reaction. Superoxide dismutase, catalase, hydroxyl radical scavengers and an iron chelator, diethylenetriaminepenta-acetic acid, inhibited the lipid peroxidation, indicating that the lipid peroxidation is initiated by a hydroxyl radical generated from the interaction of H2O2 with ferrous iron released from ferritin. PMID- 1934169 TI - Properties of androsterone-sulfating sulfotransferase in female rat liver. AB - Some properties of androsterone (AD)-sulfating sulfotransferase (ST) present in female rat livers were characterized. Based on the substrate specificities of the enzyme preparation obtained by anion exchange chromatography and 3' phosphoadenosine 5'-phosphate (PAP)-agarose affinity chromatography, AD-ST was supposed to be among isoenzymes of hydroxysteroid STs. The identity of the AD-ST with the isoenzymes of hydroxysteroid ST, however, remains unclear at present. The enzyme preparation revealed a wide range of native molecular weight with a major Mr of some 600000. The AD-ST did not appear to have a homogeneous isoelectric point, because the enzymatic activity was spread over a wide range of the pH gradient, centering around pH 6.6 on chromatofocusing. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the AD-ST showed a subunit with Mr of 30000, which was similar to the hydroxysteroid STs purified previously. Under denaturing conditions the subunit was demonstrated to be composed of three protein species containing distinct pI values (pI 6.1, 6.7 and 7.2). The AD-ST was thus supposed to be an oligomer with high molecular weight, in which the subunits of different pI values are assembled in various association numbers. PMID- 1934171 TI - Some cytotoxicological aspects of ethyl and fluoroethyl alkanesulfonates in Escherichia coli: role of fluorine substitution. AB - Several fluoroethyl derivatives of alkanesulfonates and N-nitrosourea were tested for cytotoxicity and mutagenicity in E. coli K12 AB1157. Cytotoxicity was potentiated by fluorine substitution in the alkyl moiety of the ethylating agents. Mutagenicity was strongly suppressed by fluorine substitution in the alkanesulfonates, but not in the N-nitrosourea. The capacity to induce the SOS repair network was suppressed, as was mutagenicity, in alkanesulfonates, but not in N-nitrosourea. The potentiating effect of fluorine on the cytotoxicity of alkanesulfonates seems to be due to an as yet unknown killing mechanism. An appreciable suppressive effect on the mutagenicity and the SOS induction is worth notice for the biological role of fluorine substitution in alkylating agents. PMID- 1934172 TI - Human pre-interleukin 1 alpha and beta: structural features revealed by limited proteolysis. AB - Both pre-interleukin 1 alpha and beta (pre IL 1 alpha and beta) are proteolytically processed into extracellular mature forms of IL 1 alpha and beta. Since pre IL 1 alpha is shown to be biologically active, there may be other reasons for the proteolytic processing of IL 1 alpha and presumably, for IL 1 beta also. In order to examine the possibility that structural stabilization may be associated with the proteolytic processing of pre IL 1 alpha and beta, we investigated the structural features of pre IL 1 alpha and beta by the combination of limited proteolysis and immunoprecipitation with antibodies to the NH2-terminal halves or COOH-terminal halves of pre IL 1 alpha or beta. Both trypsin and V8 protease digested the NH2-terminal halves of pre IL 1 alpha and beta more easily than the COOH-terminal halves of pre IL 1 alpha and beta, yielding structurally stabilized "mature" forms of IL 1. Both trypsin and V8 protease yielded a fragment similar in size to mature IL 1 alpha from pre IL 1 alpha. In contrast, trypsin digested pre IL 1 beta into fragments smaller in size than mature IL 1 beta, while V8 protease yielded a fragment similar in size to mature IL 1 beta. Furthermore, mature IL 1 beta, once processed and released from cells, was resistant to trypsin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934173 TI - Cisplatin suppository: preparation, release characteristics and clinical evaluation. AB - Cisplatin (CDDP) has attracted attention as a chemotherapeutic agent for the treatment of uterine endometrial carcinoma but causes serious side effects, including renal toxicity. CDDP suppositories containing NaCl at different concentrations were prepared to enhance the efficacy and to reduce the side effects of CDDP. The release characteristics, melting point and viscosity of the suppositories were first studied. The rate of CDDP release increased as the NaCl concentration increased: it was 12% 12 h after administration of suppositories containing no NaCl, but 32% with 0.2% NaCl. The melting point was raised by addition of NaCl: 35.5 degrees C without NaCl and 36.5 degrees C with 0.2% NaCl. Addition of 0.2% NaCl doubled the viscosity. Clinically, the suppository containing 0.06% NaCl was given to 3 patients with endometrial carcinoma twice a week for 3 weeks to examine serum CDDP levels and endometrial absorption. Patients with endometrial carcinoma showed different peak plasma platinum (Pt) levels which were as low as 0.12, 0.06 and 0.22 micrograms Pt/ml with similar patterns of change in the level. Radiographic analysis revealed many Pt particles in sections of necrosed endometria after 21d of the treatment. No side effects of CDDP were found in biochemical testing or subjective symptoms. PMID- 1934174 TI - Interaction of recombinant human interferon-gamma with liposomes. AB - The interaction of recombinant human interferon-gamma (IFN) with egg phosphatidylcholine liposomes was studied. IFN which binds to liposomes was dependent on the liposomal charge and pH, and a preferential binding was observed in negatively charged liposomes at pH 7.4-10. Electron-microscopic observation showed that the increased liposomal turbidity induced by IFN was due to liposomal aggregation, and the increased turbidity could be decreased by the addition of NaCl. Thus, ionic binding may participate in this interaction. But, when the incubation time was longer, the liposomal aggregation was not decreased by the addition of NaCl, and the leakage of the entrapped marker, calcein, was observed. Electron-microscopic analysis showed that this leakage resulted from the morphological change of liposomes. From these findings, ionic binding may participate in the interaction between IFN and liposomes and then develop a morphological change in negatively charged liposomes under the neutral pH condition. PMID- 1934175 TI - Properties of novel aldose reductase inhibitors, M16209 and M16287, in comparison with known inhibitors, ONO-2235 and sorbinil. AB - Properties and efficacies of novel aldose reductase (AR) inhibitors, M16209 (1-(3 bromobenzo[b]furan-2-ylsulfonyl)hydantoin) and M16287 (1-(3-chlorobenzo[b]furan-2 ylsulfonyl)hydantoin), were examined in vitro and in vivo, compared with known AR inhibitors, ONO-2235 and sorbinil. These four compounds inhibited partially purified aldose reductases from various origins, and the potencies of M16209 and M16287 were on the whole similar to ONO-2235, and were greater than that of sorbinil. The IC50 values of the four AR inhibitors did not substantially depend on the substrate used. Kinetic studies of inhibition of partially purified bovine lens (BLAR) revealed that M16209, M16287 and sorbinil were uncompetitive with glyceraldehyde and noncompetitive with nicotineamide adenine dinucleotide phosphate (NADPH), whereas ONO-2235 was noncompetitive with both glyceraldehyde and NADPH. Aldose reductase became less sensitive to the four inhibitors as enzyme purification progressed, although the susceptibility to inhibition was partially reversed by incubation with dithiothreitol. In addition, the four compounds slightly affected those enzymes of carbohydrate and glutathione metabolism which were tested. M16209 and M16287 prevented sorbitol accumulation in isolated rat tissues as potently as ONO-2235 and sorbinil. M16209 and M16287 were effective in the prevention of galactosemic cataracts and amelioration of diabetic neuropathy with almost the same potency, while ONO-2235 was effective only in neuropathy, and sorbinil was effective in galactosemic cataracts and diabetic neuropathy with a different potency. These results indicate that M16209 and M16287 are potent aldose reductase inhibitors, which could be applicable to treatment for diabetic complications. PMID- 1934176 TI - Inhibitory effect of 2-(E-2-alkenoylamino)ethyl alkyl sulfides on gastric ulceration in rats. II. Structure and activity relationships of 2-(E-n or Z-n Decenoylamino)ethyl alkyl sulfides. AB - The analogues of 2-(E-n or Z-n-decenoylamino)ethyl carbamoylmethyl sulfide, including the modifications of sulfide portion, double bond in decenoyl chain and alkyl sulfide moiety, were synthesized and their inhibitory effects on stress induced ulceration in rats were compared. Replacing the sulfura atom by methylene group or oxygen atom reduced the effect of potency. Saturation of the double bond in the decenoyl chain tended to reduce the anti-ulcerogenic activity in rats. There was no relationship between the position of double bond in decenoyl chain and the pharmacological activity. On the other hand, compounds with E configuration showed stronger anti-ulcer activity than the corresponding Z-type of compounds. Among 9 kinds of S substituted alkyl groups for carbamoylmethyl, 2 (E-2-decenoylamino)ethyl 2-cyclohexylethyl sulfide showed the most potent anti ulcerogenic activity in rats and also showed the lowest acute toxicity in mice. PMID- 1934178 TI - Imidazo[1,2-a]pyridines. I. Synthesis and inotropic activity of new 5-imidazo[1,2 a]pyridinyl-2(1H)-pyridinone derivatives. AB - A series of 1,2-dihydro-5-imidazo[1,2-a]pyridinyl-2(1H)-pyridonones was synthesized and evaluated for positive inotropic activity, 1,2-Dihydro-5 imidazo[1,2-a]pyridin-6-yl-6-methyl-2- oxo-3-pyridinecarbonitrile (11a) hydrochloride monohydrate (E-1020) was found to be a potent and selective inhibitor of phosphodiesterase III and a long-acting, potent, orally active positive inotropic agent. Additional imidazo[1,2-a]pyridin-2-yl (3a), -3-yl (16), -7-yl (20) and -8-yl (24a) compounds were also prepared. Altering the pyridine substitution from the 2-position to the 6-position produced a 2-fold increase in the i.v. cardiotonic potency (ED50) from 52 to 23 micrograms/kg, while substitution at the 3-, 7- or 8-position reduced potency. In the 2-positional isomers, introduction of halogen groups enhanced the activity and 3-chloro-1,2 dihydro-5-(6-fluoroimidazo[1,2-a] pyridin-2-yl)-6-methyl-2(1H)-pyridinone (3u) was the most potent (i.v. ED50 11 micrograms/kg) in this series. E-1020 is presently under development for the treatment of congestive heart failure. PMID- 1934179 TI - Synthesis of cobalt(II) and nickel(II) complexes of Ceclor (cefaclor) and preliminary experiments on their antibacterial character. AB - Cobalt(II) and nickel(II) complexes of the antibacterial drug Ceclor have been synthesized and characterized on the basis of their elemental analysis, molar conductance, magnetic moment and electronic and infrared spectral data. These complex have been, then subjected to screening for their antibacterial properties against bacterial species such as Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli. In comparison to uncomplexed Ceclor, the metal complexes have been shown to be more antibacterial. PMID- 1934177 TI - Constituents of the roots of Boerhaavia diffusa L. III. Identification of Ca2+ channel antagonistic compound from the methanol extract. AB - Two known lignans, liriodendrin and syringaresinol mono-beta-D-glucoside, have been isolated from the methanol extract of the roots of Boerhaavia diffusa L. (Nyctaginaceae), and the former compound was found to exhibit a significant calcium (Ca2+) channel antagonistic effect in frog heart single cells using the whole-cell voltage clamp method. Reexamination of the carbon-13 nuclear magnetic resonance (13C-NMR) spectra of these compounds was also carried out by the use of two-dimensional NMR techniques including a 1H-detected heteronuclear multiple bond connectivity (HMBC) experiment, and it was found that the previous signal assignments for C-1' and C-4' have to be revised. PMID- 1934180 TI - Immunohistochemical demonstration of calcium-binding protein regucalcin in the tissues of rats: the protein localizes in liver and brain. AB - A calcium-binding protein, regucalcin, was isolated from rat liver cytosol. Rabbit-anti-regucalcin antiserum, which was raised against regucalcin conjugated by glutaraldehyde to bovine serum albumin, was applied to glutaraldehyde-fixed whole mounts and subsequently visualized using the peroxidase-antiperoxidase methods. Rat hepatic regucalcin immunoreactivity was most pronounced in the liver and brain of rats, while it was not seen in the duodenum, testicle, spleen, lung and smooth muscle (bladder), and appeared only slightly in the kidney and heart. Control experiments using non-immune sera or adsorbed anti-rat liver regucalcin antiserum showed no staining. The present finding suggests that regucalcin localizes in the liver and brain of rats. PMID- 1934181 TI - Antibacterial activity of two chalcones, xanthoangelol and 4-hydroxyderricin, isolated from the root of Angelica keiskei KOIDZUMI. AB - Two chalcones, xanthoangelol (I) and 4-hydroxyderricin (II), isolated from the root of Angelica keiskei KOIDZUMI (Umbelliferae) showed antibacterial activity against gram-positive pathogenic bacteria. The activity of I on Micrococcus luteus IFO-12708 (minimum inhibitory concentration (MIC), 0.76 microgram/ml) was the same potency as that of gentamicin, which is used as a standard. Although the activity of both chalcones on plant-pathogenic bacteria was lower than that of streptomycin sulfate, used as a positive control, they also exhibited growth inhibitory effects. The antibacterial activity of I isolated from Angelica keiskei KOIDZUMI is being reported here for the first time. The growth-inhibitory effect of II on plant-pathogenic bacteria is also reported for the first time in this paper. PMID- 1934182 TI - Inhibition of experimental pulmonary metastasis of Lewis lung carcinoma by orally administered beta-glucan in mice. AB - The inhibitory effect on experimental pulmonary metastasis of Lewis lung carcinoma (3LL) of SSG, a (1----3)-beta-D-glucan obtained from the fungus Sclerotinia sclerotiorum IFO 9395, administered orally was examined in mice. Oral administration of SSG for 10 consecutive days just after the intravenous implantation of tumor cells significantly inhibited the experimental pulmonary metastasis of 3LL at a dose of 2000 micrograms. However, SSG administered orally involving other timings was less effective. In comparison with oral administration, SSG was effective when administered intraperitoneally for 10 consecutive days at a dose of 200 micrograms. These results suggest that SSG given by both parenteral and nonparenteral routes is effective in the inhibition of experimental pulmonary metastasis of tumors. PMID- 1934183 TI - Percutaneous absorption of bromhexine in rats. AB - The percutaneous absorption of bromhexine (BH), an expectorant drug, through rat skin was examined in vitro and in vivo. BH in free base form penetrated better than the hydrochloride through the skin. When the in vitro penetration of BH was compared using Plastibase, macrogol and sucrose ester of fatty acid F-160 (DK ester) formulations, the DK-ester formulation showed the best penetration of BH of the three. The addition of Azone (3%) or lauric acid (BH: lauric acid molar ratio, 1:1) considerably increased BH penetration to a relatively large penetration rate. The plasma levels of BH after in vivo application of the DK ester formulation with Azone or lauric acid (0.6 g/3.8 cm2) were also higher than those after the formulation without an enhancer, and a constant plasma level (20 50 ng/ml) was obtained during the application for 48 h. However, the bioavailability was low, 2.5 and 2.7% respectively. When the amount of BH remaining in DK-ester ointment and the skin after an 18-h application was measured, the BH content in the ointment was 88.6 +/- 8.0% for the formulation without Azone and 93.7 +/- 6.9% for that with Azone. The low penetration and low bioavailability observed will thus be due to the high drug retention of the base. PMID- 1934184 TI - Pharmacokinetics of [6]-gingerol after intravenous administration in rats. AB - A high-performance liquid chromatographic method to determine [6]-gingerol, a pungent constituent of ginger, in rat plasma was developed and a pharmacokinetic study was performed in rats. Quantitative analysis with high reproducibility was achieved for [6]-gingerol over the concentration range of 0.2-40 micrograms/ml. After bolus intravenous administration at a dose of 3 mg/kg, the plasma concentration-time curve was described by a two-compartment open model. [6] Gingerol was rapidly cleared from plasma with a terminal half-life of 7.23 min and a total body clearance of 16.8 ml/min/kg. Serum protein binding of [6] gingerol was 92.4%. PMID- 1934185 TI - Mitogenic and colony-stimulating factor-inducing activities of polysaccharide fractions from the fruit bodies of Dictyophora indusiata Fisch. AB - Biological effects (mitogenic and colony-stimulating factor (CSF)-inducing activities) of five homogeneous polysaccharides and a conjugated polysaccharide fraction isolated from the fruit bodies of Dictyophora indusiata Fisch. were investigated. Fucomammogalactan (T-3-Ad) and conjugated polysaccharide fraction (T-2-A) exhibited significant mitogenic and CSF-inducing activities. Among two beta-(1----6)-branched (1----3)-beta-D-glucans (T-4-N and T-5-N), only T-4-N showed both mitogenic and CSF-inducing effects. Partially O-acetylated (1----3) alpha-D-mannans (T-2-HN and T-3-M') did not show these effects. PMID- 1934186 TI - Conformational studies of cyclo(L-Phe-L-Pro-Gly-L-Pro)2 by 13C nuclear magnetic resonance. AB - The 13C-NMR spectrum (Fig. 2,1) of cyclooctapeptide cyclo(L-phe-L-Pro-Gly-L-Pro)2 (A) in CDC13 suggested that its conformation involved the coexistence of two kinds of C2-symmetric conformation with trans-trans-trans-trans and cis-trans trans-trans forms. Adding 0.5 equivalent of CsSCN or one equivalent of DL-Phe OMe.HCl to the solution of cyclopeptide (A) in CDC13 yielded 13C-NMR spectra (Fig. 2,2 and Table I) which suggested a single C2-symmetric conformation with trans-trans-trans-trans form, resulting from the formation of complexes with CsSCN or DL-Phe-OMe.HCl. The 13C-NMR spectrum of complexes of A with DL-Phe OMe.HCl displayed separate resonances for C(gamma), C(o), C(m), C(alpha), and C(beta) of D-Phe-OMe.HCl and L-Phe-OMe.HCl (Table I). PMID- 1934187 TI - Effect of molecular weight in amphipathic polyethyleneglycol on prolonging the circulation time of large unilamellar liposomes. AB - The effect in mice of the molecular weight of polyethyleneglycol on prolonging the circulation time of large unilamellar liposomes (LUVs) was examined using four different distearoyl N-(monomethoxy polyethyleneglycol succinyl) phosphatidylethanolamines (DSPE-PEGs). The molecular weights tested were 1000, 2000, 5000 and 12000. Incorporation of 6 mol% of DSPE-PEG in LUV composed of distearoylphosphatidylcholine (DSPC) / cholesterol (CH) (1:1 in molar ratio) increased the blood circulation half-life significantly more than those without DSPE-PEG derivatives. DSPE-PEGs with molecular weights of 1000 and 2000 prolonged the circulation time of liposomes more than other DSPE-PEGs with higher molecular weights, such as 5000 and 12000. Their effects are also higher than ganglioside GM1, a well described glycolipid with this effect. DSPC/CH LUV-incorporated DSPE PEG with a molecular weight of 2000 displayed a high concentration in the blood, approximately 40% of the dose, 6 h after the injection. PMID- 1934188 TI - Structures of two new steroidal glycosides, soladulcosides A and B from Solanum dulcamara. AB - The structures of two new steroidal glycosides named soladulcosides A and B, isolated from the aerial parts of Solanum dulcamara including new sapogenols, were elucidated as (22R, 25R)-3 beta, 15 alpha, 23 alpha-trihydroxy-5 alpha spirostan-26-one 3-O-alpha-L-rhamnopyranosyl-(1----2)-beta-D-glucopyranoside and (22R, 25R)-3 beta,23 alpha-dihydroxy-5 alpha-spirostan-26-one 3-O-alpha-L rhamnopyranosyl-(1----2)-[alpha-L-rhamnopyranosyl-(1----4)]- beta-D glucopyranoside, respectively. PMID- 1934190 TI - Estimating tissue permeability and other bioelectrical parameters using membrane voltage and short-circuit current. AB - Evaluating the acute toxic effects of drugs or toxins is based mainly on studies which require the use of light microscopy. Recently, the effects of such substances on biological membranes, such as the nasal membrane, has been studied using the traditional Ussing chambers, which make it possible to study the transepithelial flux of drugs across membranes and to measure some bioelectrical parameters. A model is described, with which the changes in the membrane permeability, for sodium, potassium and chlorine, can be calculated directly, based on values obtained from the Ussing chamber system. Also, an experiment is described for evaluating the toxic effects of the cholera toxin B subunit, by measuring these changes in isolated rabbit nasal mucosa. PMID- 1934189 TI - Synthesis and antitumor activity of 7-(N-glycosylamino)-indolo[3,2-b]quinolines. AB - Novel indolo[3,2-b]quinolines (1d-g), introduced at the 7-position with an N glycosylamino group, were prepared and their antitumor activities against leukemia P388 in mice were examined. The N-Galactopyranosylamino derivative (1e) was a much more potent anti-leukemia compound (optimal dose = 25 mg/kg, T/C greater than 333%, cure 5/6) than lead compound 1a. PMID- 1934191 TI - Antiviral activity of polyoxomolybdoeuropate PM-104 against human immunodeficiency virus type 1. AB - A polyoxomolybdoeuropate PM-104 (NH4)12H2[Eu4(MoO4)(H2O)16(Mo7O24)4].13H2O was found to be a potent inhibitor of the growth of human immunodeficiency virus type 1 (HIV-1), a causative agent of acquired immunodeficiency syndrome (AIDS). On the basis of TI50 [median cytotoxic concentration (CC50)/median effective concentration (EC50)], the in vitro anti-HIV-1 activity of PM-104 is favorably comparable to that of a heteropolyoxotungstate PM-19 K7[PTi2W10O40].6H2O, which is one of the most potent HIV-1 inhibitors among the polyoxometalates so far tested. The heteropolyoxomolybdate with a potent anti-HIV-1 activity is introduced for the first time in this communication. PMID- 1934192 TI - Conformational changes of the phosphatidylcholine headgroup due to membrane dehydration. A 2H-NMR study. AB - The influence of hydration on the orientation of the phosphocholine dipole in bilayer membranes was studied with nuclear magnetic resonance. The phosphocholine headgroup of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) was deuterated at the two methylene segments. Phosphorus-31 and deuterium nuclear magnetic resonance measurements were made as a function of hydration in the range of 10-70 wt.% H2O revealing a distinct change in the alignment of the phosphocholine headgroup. With decreasing hydration the N+ end of the phosphocholine head group dipole moves closer to the hydrocarbon layer. The conformational change induced by the loss of water molecules at the membrane surface is qualitatively similar to that observed upon addition of polyhydroxyl compounds. PMID- 1934193 TI - Effects of fluorophore structure and hydrophobicity on the uptake and metabolism of fluorescent lipid analogs. AB - Cellular transport and metabolism of fatty acids are integral components of lipid metabolism, but the mechanisms and regulation involved are poorly understood. A variety of commercially available fluorescent analogs of fatty acids, are potentially useful probes for the study of lipid metabolism by such techniques as cell sorting and fluorescence microscopy. We have screened a series of fluorescent fatty acids to identify analogs that would reliably simulate the metabolic behavior of natural fatty acids; i.e., similar kinetics of transport, of intracellular movement, and of metabolic fate. The metabolic behavior of these analogs was compared with those of some naturally occurring fatty acids in HepG2 cells, which are a good model of some aspects of hepatic function. Fluorescent analogs containing polar fluorophores yielded the lowest rates of cellular uptake and conversion to acylated lipid products. Similarly, fluorescent analogs with the fluorophore located near the carboxylic acid group were poorly metabolized. Fatty acid analogs containing anthracene or pyrene at the n-terminus of the acyl chain were the most extensively incorporated into cellular lipids. The types and amounts of labeled lipid products formed from these analogs and from natural fatty acids were similar. Pyrene-labeled analogs have spectral properties that can be measured fluorometrically at very low concentrations. Therefore, we compared the cellular metabolism of 12-(1-pyrenyl)dodecanoic acid with those of palmitic and oleic acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934194 TI - Cholesterol-multilipid interactions in bilayers. AB - To extend our knowledge of model membrane systems based upon one lipid component, multi-lamellar bilayers were made of cholesterol with two phospholipids in equimolar ratio, and the enthalpy change delta H of the main phase transition of the temary mixture was measured by differential scanning calorimetry (DSC) as a function of increasing cholesterol concentration c. The lipids were saturated phosphatidylcholines CnPC of acyl chain length n, and as the n of the two lipids became more different (from C13PC/C14PC to C14PC/C15PC to C14PC/C18PC to C14PC/C19PC) distinct breaks in the delta H versus c plots were observed. These mixtures displayed only one broad DSC endotherm. Mixtures of an unsaturated lipid C18: 1PC (dioleoyl) with C16PC or with C18PC showed two peaks, with each peak being associated with its parent lipid. However, the delta H versus c plots for each of these peaks showed an initial independence of cholesterol concentration followed by a dependence on cholesterol concentration. These results indicate that, in lipid mixtures, the type of interaction of cholesterol with each lipid component depends on the concentration of cholesterol present. PMID- 1934195 TI - The effect of lung surfactant apolipoproteins B/C on the chemical shift anisotropy of sn-2-[1-13C]dipalmitoylphosphatidylcholine. AB - Nuclear magnetic resonance spectroscopy has been used to investigate the effect of the lung surfactant apolipoproteins B/C on dipalmitoylphosphatidylcholine to address the mechanism by which the adsorption rate of phospholipids from the bulk to the air/water interface is enhanced. Apolipoproteins B/C were isolated from bovine lung and separated from associated lipids by lipophilic Sephadex column chromatography. Amino acid analysis indicated the presence of both apolipoproteins B and C. The 13C chemical shift anisotropy of DPPC was determined as a function of temperature. Previous workers (Wittebort et al., Biochemistry, 20 (1981) 3487-3502) have concluded that the observed magnitude of the chemical shift anisotropy of the carbonyl group of the sn-2 acyl chain in pure DPPC is a result of rapid rotation about an axis along the length of the phospholipid both in the gel and liquid crystalline state. The orientation of the carbonyl group with respect to the axis of diffusion, however, undergoes an approximately 25-30 degrees shift in passage from the gel to liquid crystalline state, with the intermediate, rippled (P beta') state composed of an exchange between these two orientations. The presence of physiological concentrations SP-B/C reduced the width of the anisotropy of DPPC below but had no effect on lipids above the main phase transition temperature. This suggests that SP-B/C has a general effect on the entire assembly of lipids. The temperature of the onset of the orientational change is lowered indicating a portion of the lipids are affected by the lung surfactant apolipoproteins. PMID- 1934196 TI - Chemical synthesis and surface activity of lung surfactant phospholipid analogs. III. Chiral N-substituted ether-amide phosphonolipids. AB - A homologous series of chiral (R) ether-amide phosphonolipid analogs of naturally occurring (R) glycerophospholipids were synthesized and characterized for their interfacial behaviors. The phosphonolipids possess isoteric ether, amide, and phosphonate functions at positions corresponding to the sn-1, sn-2, and sn-3 ester functions, respectively, of naturally occurring glycerophospholipids. All compounds were synthesized with disaturated C16:0 alkyl/acyl moieties to give structural analogy with dipalmitoyl phosphatidylcholine (DPPC), the major glycerophospholipid component of lung surfactant. Further substitutions at the headgroup nitrogen were also used to generate differences in headgroup size and polarity in the synthetic compounds. The surface activity of the ether-amide phospholipids was investigated in terms of adsorption to the air-water interface, together with studies of dynamic respreading after monolayer collapse and surface tension lowering in dynamically compressed spread films and dispersions. Results showed that several ether-amide phosphonolipids had more rapid adsorption and improved dynamic respreading behavior compared to DPPC, plus the ability to lower surface tension into the range of less than 1 to 4 mN/m in spread films and in dispersions under dynamic conditions. In combination with a series of diether phosphonolipids synthetized in a companion study [1], these ether-amide compounds are useful in the development of molecular structure-surface activity correlates for lung surfactant-related materials, and should assist in investigating the specificity of interactions between phospholipids and other pulmonary biological molecules. PMID- 1934197 TI - High pressure 2H nuclear magnetic resonance study of the gel phases of dipalmitoylphosphatidylcholine. AB - The 2H-NMR lineshapes of dipalmitoylphosphatidylcholine perdeuterated in the acyl chains were studied in a 15% dispersion in water as a function of pressure from 1 bar to 5 kbar over the temperature range from 7 degrees C to 75 degrees C. Increasing pressure in the gel state had the same effect as lowering the temperature: the lineshape gradually changed from a motionally averaged to a rigid lattice type spectrum with much of the intensity in the shoulders at +/- 63 kHz. At very high pressures and low temperatures (7 degrees C, 2.5 kbar; 25 degrees C, 5 kbar) even the methyl portion of the spectrum became a rigid lattice type spectrum at +/- 21 kHz. In addition to the liquid crystalline phase, five gel phases were detected. Using different techniques to determine the phase transitions, a general pressure-temperature phase diagram was constructed. PMID- 1934198 TI - Transferrin receptor expression in oral tumors. AB - Transferrin receptor expression in oral tumors was examined by staining with monoclonal antibody against the human transferrin receptor. The cells with positive reaction were recognized in the basal and parabasal layers of the normal epithelium. The staining was found in all the malignant tumors but not in the benign tumors. These results suggest that the immunohistochemical analysis of the transferrin receptor is useful for the diagnosis of oral malignant tumor in addition to the clinical and pathological examinations. PMID- 1934199 TI - Study on cholesteryl ester transfer activity in coronary heart disease. AB - The net cholesterol transfer activity from high density lipoprotein (HDL) to low density lipoprotein (LDL) was determined in the patients with coronary heart disease (CHD) to examine its effect on the pathogenesis of arteriosclerosis. Furthermore, in the CHD patients with high HDL cholesterolemia (more than 60 mg/dl), the HDL particle size was measured by high performance liquid chromatography. A significant cholesteryl ester transfer activity (P less than 0.02) was noted in the CHD patients with low HDL cholesterolemia (less than 60 mg/dl). The rate of cholesteryl ester transfer activity (cholesteryl ester transfer activity/hour) inversely correlated with the serum HDL cholesterol value (r = -0.483, P = 0.096) in the patients with CHD. These results suggest that an increase of CETA caused a low HDL cholesterol value in the CHD patients with low HDL cholesterolemia and it may have the risk of causing CHD. However, an increase of the CETA was not found in the CHD patients with high HDL cholesterolemia compared to the normal subjects, the HDL particle size being significantly greater than that in the normal subjects. In the CHD patients with high HDL cholesterolemia, the large size of HDL may have the risk of causing CHD. PMID- 1934200 TI - Protective effects of calcium antagonist (nitrendipine) on calcium ionophore A23187-induced liver cell injury. AB - Calcium ionophore A23187-induced liver damage was studied in perfused rat liver and isolated hepatocytes. Two groups of calcium antagonists, dihydropyridine-type and nondihydropyridine-type, were examined for their protective effects on A23187 induced liver damage. The former calcium antagonist inhibited cell damage at pharmacological doses, whereas nondihydropyridine-type calcium antagonists were unable to prevent A23187-induced cytotoxicity. Different inhibitors, such as cAMP phosphodiesterase inhibitor OPC3689, calmodulin inhibitor W-7, and C-kinase inhibitor H-7, were tested in isolated hepatocytes to determine whether intracellular signal transduction systems are involved in the liver cell injury produced by A23187. Calcium ionophore A23187-induced LDH activity of the medium was depressed by W-7 and H-7 to 55 +/- 4% and 63 +/- 4% of controls (p less than 0.01), respectively. However, OPC3689 did not show a protective effect. We conclude that A23187-induced liver cell injury was inhibited by dihydropyridine type calcium antagonists which may interfere with activation of calmodulin and C kinase. PMID- 1934201 TI - Implementing a DNR policy: promise and perils. PMID- 1934202 TI - Evaluation of a "do not resuscitate" policy in intensive care. AB - The decision to withhold cardiopulmonary resuscitation from a patient within an intensive care unit (ICU) may be a difficult but appropriate one for which there are few guidelines. We describe the formulation of a Do Not Resuscitate (DNR) policy in our multidisciplinary ICU. To evaluate the effect of implementation of the DNR policy on physician practice and on communication among physicians, nurses, patients and their families, we interviewed physicians and nurses caring for patients designated DNR before (n = 8) and after (n = 17) implementation of the DNR policy. We found that DNR orders in the ICU were not infrequent (2-3 per week). All patients designated DNR were either irreversibly ill or not responsive to maximal therapy, and 22 of 25 were not competent. The DNR order was not accompanied by withdrawal of other therapy in 50% of cases and one patient recovered and was discharged from hospital. The implementation of the DNR policy encouraged greater physician consultation with other physicians, patients and their families. Although there were differences in perception of communication between physicians and nurses, we believe that the DNR policy influenced physician practice and enhanced overall communication in the ICU. PMID- 1934203 TI - Coronary haemodynamics and myocardial metabolism during weaning from mechanical ventilation in cardiac surgical patients. AB - The present clinical study was undertaken to assess the alterations in myocardial metabolism and coronary haemodynamics during weaning from mechanical ventilation in postoperative cardiac surgical patients. Global and regional myocardial blood flow and metabolism were assessed using a dual port coronary sinus-great cardiac vein thermodilution catheter in 17 patients who had undergone coronary revascularization and who were being weaned from mechanical ventilation. Anaerobic myocardial metabolism, as demonstrated by the production of myocardial lactate, manifested in 8 of 17 patients during at least one of the weaning phases. There were no differences in coronary blood flow between patients who produced myocardial lactate and those who maintained aerobic cardiac metabolism. However, lactate producers exhibited larger changes in systemic vascular resistance and mean arterial pressure than the non-lactate producers. This metabolic manifestation of myocardial ischaemia was not accompanied by electrocardiographic changes of ischaemia, nor presence of chest pain, and may represent another form of silent ischaemia. We conclude that despite coronary revascularization, the myocardium may remain vulnerable to ischaemic anaerobic metabolism in the immediate postoperative period. PMID- 1934204 TI - Indomethacin as a postoperative analgesic for total hip arthroplasty. AB - This prospective, randomized, double-blind trial evaluated the efficacy of rectal indomethacin as an adjunct to morphine for controlling postoperative pain. Fifty healthy patients undergoing elective hip arthroplasty were investigated. Group 1 (n = 25) received placebo suppositories, Group 2(n = 25) received indomethacin suppositories, 100 mg q8hr for five doses, starting at the end of the procedure. Both groups received morphine via a PCA pump, which recorded the amount of morphine delivered each hour. After a standardized general anaesthetic, PCA was begun in the recovery room. Pain was measured with a standard 100 mm VAS at 2, 6, 20, 28, 42 hr after surgery and the morphine consumption recorded. Over the 42-hr study period, patients in Group 2 required less morphine than those in Group 1 (34.8 +/- 21.8 mg vs 89.6 +/- 43.7, P less than 0.01). Pain scores were lower in Group 2 at 20, 28, 42 hr postoperatively. The incidence of side-effects did not differ between groups and no patient had excessive postoperative bleeding. The combination of indomethacin and morphine provided superior pain relief to morphine alone even though the control group had liberal access to morphine. This synergistic effect would make indomethacin a useful adjunct to intramuscular or epidural narcotics. PMID- 1934205 TI - Comparison of epidural and patient-controlled intravenous morphine following joint replacement surgery. AB - The authors conducted a randomized, prospective study comparing epidural morphine with patient-controlled intravenous (iv) morphine in 30 patients recovering from total hip or total knee arthroplasty. Six, 18, and 24 hr postoperatively, patients used a 10 cm visual-analogue scale to indicate both their current degree of discomfort and the maximum discomfort they had experienced since the previous evaluation. Pain at the time of evaluation did not differ between patients receiving epidural (2.6 +/- 0.4 cm, mean +/- SEM) and patient-controlled iv morphine (3.4 +/- 0.3 cm). However, patients who received epidural morphine recalled less pain during the period preceding evaluation (4.2 +/- 0.5 cm) than did those receiving patient-controlled analgesia (5.5 +/- 0.4 cm, P less than 0.05). Patients receiving epidural morphine were more likely to require treatment for pruritus (4 of 15) than patients who received patient-controlled iv morphine (none of 15, P less than 0.05). Minimum respiratory rates were lower in patients receiving epidural morphine (15.0 +/- 0.3) than in those receiving patient controlled analgesia (16.5 +/- 0.4, P less than 0.05), but no patients required treatment for respiratory depression. The authors conclude that epidural morphine may provide more consistent analgesia following joint replacement surgery than patient-controlled morphine; however, there is a higher incidence of side-effects with the epidural technique. PMID- 1934206 TI - Residual curarization in the neonate after caesarean section. AB - The transplacental transfer and the neonatal effects of atracurium 0.3 mg.kg-1 (ED95) were compared with those of d-tubocurarine at the usual clinical dose of 0.3 mg.kg-1 (ED90) in 46 patients undergoing elective Caesarean section. The atracurium group (25 patients) was similar to the d-tubocurarine group (21 patients) as far as age, parity and time intervals between precurarization, induction, skin incision, muscle relaxant administration, hysterotomy and birth. The transplacental transfer of atracurium was lower than that of d-tubocurarine, with a feto-maternal ratio of 9 +/- 3% for atracurium and 12 +/- 5% for d tubocurarine (P less than 0.05). The transplacental transfer of laudanosine was low at 14 +/- 5%, with blood levels of 0.101 +/- 0.032 microM.L-1 in the umbilical vein. Newborns in the two groups were comparable in terms of Apgar scores at one, five and ten minutes, as well as for NACS scores (neurological and adaptive capacity scoring test) at two and 24 hours after birth. However, at 15 min after birth, only 55% of newborns in whom the mothers received atracurium had a normal NACS score (greater than or equal to 35/40) compared with 83% of newborns in whom the mothers received d-tubocurarine (P less than 0.05). Further analysis of the five variables related to active muscle tone revealed that the modal score for active extension of the neck of newborns from the atracurium group was lower than for newborns from the d-tubocurarine group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934207 TI - Pulse oximetry during ketamine anaesthesia in war conditions. AB - Ketamine anaesthesia with spontaneous breathing of air is a common method of anaesthesia in Red Cross hospitals for war wounded. Arterial oxygen saturation of 65 patients was measured with a portable pulse oximeter during the anaesthesia and the first 30 min of recovery. The patients were young (12-47 yr), haemodynamically stable and underwent peripheral surgery. Fifty-seven measurements were free from artefacts and were analyzed. The results showed that during induction six patients (11%) had a brief period (40-420 sec) of oxygen saturation under 90%. Two of these patients showed signs of upper airway obstruction and four breathed normally. During maintenance one patient had short periods (40-80 sec) of saturation under 90%, when he snored. No periods of desaturation occurred during the recovery period. It is concluded that arterial oxygen saturation remained acceptable when patients breathed air during ketamine anaesthesia. PMID- 1934209 TI - Blood product utilization and management in Canada. AB - The utilization of blood for transfusion in Canada has remained at 900,000 950,000 units p.a. for the past six years. Donation has decreased slightly from a peak of 1,200,000 units p.a. in 1989. The use of fresh plasma and cryo precipitate has decreased while the use of platelets has doubled in the past six years. The increased use of albumen cannot be explained. In Vancouver, all anaesthesia residents take a compulsory transfusion medicine rotation which appears to be successful in rationalizing transfusion practice. PMID- 1934208 TI - Methods of reducing blood loss and non-blood substitutes. AB - A variety of techniques can aid the anaesthetist in reducing requirements for perioperative blood products. These include careful preoperative assessment of the patient, and employing techniques during surgery which reduce the blood pressure and help preserve the normal haemostatic mechanism. If the level to which haematocrit will be permitted to decrease is decided, then physiological crystalloid and/or colloid solutions may be used to maintain circulating volume. Where large volumes of fluids are required cardiac filling pressures should be monitored because of the complex nature of the fluid shifts which occur. There is no evidence that any one fluid (physiological crystalloids, colloids) is better than any other in terms of the incidence of perioperative morbidity. PMID- 1934210 TI - Indications for perioperative blood transfusion in 1990. AB - Rational transfusion practices are determined by clinical evaluation and utilization of appropriate laboratory tests. While the trend toward more conservative transfusion practices is laudable, blood transfusions should not be withheld because of fear of transfusion-transmitted disease. The blood supply is safer than ever before and advances in monitoring and laboratory testing are facilitating scientific approaches to blood administration. PMID- 1934211 TI - Perioperative autotransfusion: haemodilution and red cell salvaging. AB - We have treated 129 cases of massive haemorrhage during surgery using our combined autotransfusion technique (HAT and SAT). No adverse reactions or complications have been noted and additional homologous blood transfusion has not been required. In addition, circulatory dynamics have been satisfactorily maintained. Although the red cell recycle rate has been maintained at over 85%, the salvaging rate of blood in the operating field has not yet reached 80%. Approximately 30% of the surgical haemorrhage appears to be discarded with surgical sponges or flow out of the operating field. Clearly the cooperation of surgeons is an important factor for success with SAT. Success in autotransfusion may be accomplished by combinations of autotransfusion techniques. PMID- 1934213 TI - Safety of blood transfusion: the Japanese experience. AB - There are eight million blood donors in Japan. Blood is donated in units of 200 ml or 400 ml and by haemapheresis. The major problems are concerned with the transmission of infection, particularly with HIV and HTL-1 viral infections, and this leads to rejection of about 8% of donated blood. Recent emphasis has been placed on the automated screening of blood at the time of donation and the more widespread use of patient records to eliminate infected blood. PMID- 1934212 TI - Safety of blood transfusion: risks and use of predonation, the Canadian experience. AB - A variety of measures has been introduced in Canada to improve the safety of the blood supply. An autologous blood transfusion pilot study in British Columbia indicated that this form of transfusion is well tolerated and accepted in low risk patients undergoing elective breast reconstructive surgery. While the use of autologous blood in Canada is not common at present, with broad donor criteria and increased concern about the hazards of homologous blood transfusion autologous transfusion is likely to increase in Canada in the future. PMID- 1934214 TI - Spurious hyperkalaemia associated with severe thrombocytosis and leukocytosis. AB - A patient with marked thrombocytosis and leukocytosis associated with myelofibrosis was found to have spurious hyperkalaemia caused by in vitro cell lysis. Initial failure to recognize the cause of the hyperkalaemia led to an inappropriate and potentially harmful intervention in an effort to optimize the patient's preoperative status. PMID- 1934215 TI - Electrocautery-induced pacemaker malfunction during surgery. AB - We report a case of electrocautery-induced pacemaker failure that resulted in asystole in a 15-year-old girl scheduled for cardiac surgery. Her pacemaker was converted to the asynchronous mode the night before surgery. Electromagnetic interference from the unipolar electrocautery caused a reduction in the battery voltage, which allowed the digital circuitry, but not the voltage control oscillator (VCO), to work properly. Eventually the battery current drain caused VCO "lock-out," and pacemaker and battery failure. This report demonstrates that electrocautery-induced pacemaker failure can occur, even after conversion to asynchronous mode. PMID- 1934216 TI - Pulse oximetry and capnography in anaesthetic practice: an epidemiological appraisal. AB - In the evaluation of any medical technology the efficacy, effectiveness, and efficiency must each be considered before routine deployment is recommended. Since the widespread practice of patient monitoring by pulse oximetry and capnography has occurred before the performance of rigorously controlled trials, definitive proof of worth is lacking. The purpose of this review is to appraise critically the effectiveness of this technology. The assessment was performed using concepts developed in epidemiology and community medicine to establish a given factor to be causative to a given outcome. The current literature pertaining to anaesthetic adverse outcomes was reviewed, and the use of monitors evaluated against the criteria of a causal relationship. While the conclusions are based more on the absence of positive data (owing to low frequency of adverse anaesthetic occurrences) rather than negative results, it must be concluded that the effectiveness of such monitoring has yet to be demonstrated. Such a conclusion should not detract from their use, for the role of an individual factor in the complex chain of accident evolution will seldom be demonstrable. Rather, such an appraisal should encourage a clear perspective of the depth of our clinical science, and encourage more rigorous critical evaluation in the future. PMID- 1934218 TI - Myocardial contractility and ischaemia in the isolated perfused rat heart with propofol and thiopentone. AB - The effects of propofol and thiopentone on myocardial contractility and global ischaemia were evaluated using an isolated non-working perfused rat heart preparation. Contractility was assessed using a tension transducer linked to the cardiac apex, and the contractility was expressed as a ratio of the deflection size before and after infusion of the drug. Ischaemia-induced leakage of myocardial proteins and ions (potassium and magnesium) was assessed by comparing the concentrations in the effluent perfusate immediately before and after 60 min of isothermic ischaemia, in the presence of propofol, thiopentone or plain Krebs' buffer solution (control). Mean contractility ratios of 1.15 and 1.3 were obtained with control and propofol groups respectively (NS), but were reduced to 0.5 in the thiopentone group (P less than 0.001). The magnitude of the post ischaemic leakage of proteins and potassium was similar in each group; however, the post-ischaemic leakage of magnesium was greater in the thiopentone group than in the propofol or control groups. These data suggest that, compared with thiopentone, propofol is not a potent negative inotrope, and that it may cause less disturbance of myocardial magnesium homeostasis during myocardial ischaemia. PMID- 1934217 TI - Anaesthesia and the child with HIV infection. AB - The frequency of AIDS in the paediatric population is growing rapidly and is expected to get worse. The anaesthetist will participate in the care of these children in the operating room and the intensive care unit with increasing frequency and must therefore have an understanding of the many manifestations of this syndrome. Children become infected with HIV by transplacental transmission from mother to fetus in over 80% of cases. Early diagnosis in infants can be very difficult. Clinical manifestations of HIV infection in children result from damage to almost every organ system. Considerations for the anaesthetist include: the effects of medications, cardiovascular dysfunction, pulmonary disease, altered metabolism, equipment preparation, choice of anaesthetic, modes of viral transmission and psycho-social issues. PMID- 1934219 TI - Nitrous oxide does not worsen myocardial ischaemia following beta-receptor blockade in isoflurane anaesthetized dogs. AB - The effect of nitrous oxide (N2O) on ischaemic myocardium was investigated in the presence of beta-receptor blockade. Three anaesthetics were compared in each of six dogs: isoflurane 1.8% alone, isoflurane 1.4% with 50% N2O, and isoflurane 1.8% with 50% N2O. Heart rate (HR), systolic aortic blood pressure (SBP), and left atrial pressure (LAP) were held constant during the three treatments. The left anterior descending coronary artery (LAD) was cannulated and perfused with an autoperfusion circuit. Systolic segment length was measured with a sonomicrometer in the LAD and circumflex regions. Regional myocardial blood flow was measured using radioactive microspheres. Propranolol was administered intravenously and then measurements were made during imposition of a stenosis on the perfusion circuit sufficient to decrease systolic shortening by 30%. The substitution of 50% N2O for 0.4% isoflurane had no effect on systolic shortening or transmural myocardial blood flow in the ischaemic or normal region. When N2O was added to 1.8% isoflurane, systolic shortening decreased by 34.6% in the ischaemic and 57.3% in the normally perfused region, while transmural myocardial blood flow distribution did not change significantly. The decrease in shortening was therefore not due to increased ischaemia. These results were similar to those of a previous experiment which was identical except that beta-blockade was absent. It is concluded that beta-receptor blockade does not markedly alter the response of normal or ischaemic myocardium to N2O. PMID- 1934220 TI - In vitro reappraisal of the pulmonary artery catheter balloon volume-pressure relationship: comparison of four different catheters. AB - The most serious risk of the use of the flow-directed pulmonary artery (PA) catheter is PA rupture due to high balloon inflation pressure of the catheter. Previously reported measurements of PA catheter intra-balloon pressure and volume during balloon inflation were performed mostly in a static fashion, that is, measurements were performed after a certain volume of air had been injected into the balloon. In this study, simultaneous measurements of pressure and volume, in addition to a static study, were performed in vitro using four PA catheters (Abbott Opticath, Arrow Hands-Off, Baxter Edwards and Spectramed). The peak intra balloon pressure was recorded immediately before loss of resistance was felt in the inflating syringe. Contrary to previously reported studies, the peak intra balloon pressure was not the pressure exerted on the pulmonary artery wall unless the tip of the catheter was already in the peripheral pulmonary artery. The loss of resistance volume which was constant for each catheter could be used reliably as an indicator of instantaneous balloon inflation. The slower the rate of injection, the lower were the peak pressure and the injection volume at the peak pressure. The Abbott, Edwards and Spectramed catheters had similar characteristics of inflation volume and intra-balloon pressure. The Arrow catheter had higher balloon opening and plateau pressures, and a smaller balloon volume compared with the other three catheters. PMID- 1934221 TI - Intracranial pressure and brain redox balance in rabbits. AB - The effects of elevated intracranial pressure (ICP) on intracellular oxygenation and cerebrocortical blood volume (CBV) were studied in rabbits. Intracellular oxygen (O2) concentration was assessed as the level of pyridine nucleotide concentration ([NADH]) oxidation/reduction balance and relative cerebrocortical blood volume (CBV) were measured with a fibreoptic fluororeflectometer probe placed on the cerebrocortical surface. Experiments were conducted in six urethane anaesthetized, normocarbic animals at different fractions of inspired O2 (FIO2). During gradual increases in ICP, [NADH] began to increase (representing decreased intracellular mitochondrial PO2) for all values of FIO2 as ICP exceeded a threshold of 18 +/- 2.2 cmH2O (P less than 0.05). The decline in intracellular oxygenation with elevated ICP was inversely related to FIO2 (P less than 0.05). With ICP greater than 18 +/- 2.2 cmH2O, intracellular mitochondrial oxygenation showed an improvement between an FIO2 of 0.21 and 0.5 (P less than 0.05) but increasing FIO2 from 0.5 to 1.0 resulted in no statistically significant improvement in tissue redox balance. The CBV, largely representing tissue capillary blood, increased when ICP reached greater 18 +/- 1.2 cmH2O probably reflecting local autoregulation or venous distension (P less than 0.05). However, above 30 +/- 1.1 cmH2O, CBV decreased (P less than 0.05). The results demonstrate the interdependence of inspired oxygen concentration, elevated ICP, and brain intracellular oxygenation, and suggest that brain oxygen utilization deteriorates above an ICP of about 18 cmH2O. PMID- 1934222 TI - Prostanoid production and pulmonary hypertension after fat embolism are not modified by methylprednisolone. AB - Bilateral cemented arthroplasty (BCA) in anaesthetized mongrel dogs produces particulate fat and marrow embolism of the lung. Methylprednisolone sodium succinate (MPSS) has been advocated for post-traumatic fat embolism to prevent acute lung injury. We used the BCA procedure to produce acute fat and marrow embolism, and tested the efficacy of MPSS (30 mg.kg-1) in preventing physiological and pathological markers of acute lung injury. Dogs (n = 6) pre treated with MPSS demonstrated similar acute increases in pulmonary artery pressure (PAP) within one minute of BCA (17.8 +/- 7.3 mmHg) as the untreated (control n = 7) dogs (18.6 +/- 12.6). Pulmonary vascular resistance (PVR) increased to the same degree in both groups (455 +/- 323 and 319 +/- 137 dyne.sec.cm-5) and PaO2 decreased by 18.3 +/- 6.4 mmHg in the control group as opposed to 12.4 +/- 7.7 mmHg in the MPSS group within five minutes of BCA. Circulating arterial and mixed venous plasma concentrations of thromboxane B2 (TxB2) increased within one minute of BCA in both groups with no increase in the transpulmonary gradient. Arterial plasma 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) increased (0.91 +/- 0.29 ng.ml-1 and 0.87 +/- 0.43 ng.ml-1) in both groups one minute after BCA. Mixed venous 6-keto PGF1 alpha plasma concentration also increased, but a significant transpulmonary 6-keto PGF1 alpha gradient was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934223 TI - Pyloric stenosis. AB - Infantile pyloric stenosis is the most frequently encountered infant gastrointestinal obstruction in most general hospitals. Although the primary therapy for pyloric stenosis is surgical, it is essential to realize that pyloric stenosis is a medical and not a surgical emergency. Preoperative preparation is the primary factor contributing to the low perioperative complication rates and the necessity to recognize fluid and electrolyte imbalance is the key to successful anaesthetic management. Careful preoperative therapy to correct severe deficits may require several days to ensure safe anaesthesia and surgery. The anaesthetic records of 100 infants with pyloric stenosis were reviewed. Eighty five per cent of the infants were male (i.e., 5.7:1 male to female ratio) 12% were prematures. Surgical correction was undertaken at an average age of 5.6 wk, and the average weight of the infants at the time of surgery was 4 kg. A clinical diagnosis of pyloric stenosis by history and physical examination alone was made in 73% of the infants presenting to The Hospital for Sick Children. All the infants received general anaesthesia for the surgical procedure and there were no perioperative deaths. PMID- 1934224 TI - ICU admissions from an obstetrical hospital. AB - To ascertain the anaesthetic complications requiring post-anaesthetic respiratory support in a large obstetrical hospital, the hospital records of obstetrical patients admitted to an adjacent general intensive care unit (ICU) were studied. Obstetrical patients who required mechanical ventilation following anaesthetic complications were identified and their hospital records reviewed. In a ten-year period there were 61,435 women delivered at the Mater Mothers Hospital (MMH) in Brisbane, Queensland, Australia. Of these 24,161 had an anaesthetic associated with delivery including 7,452 general anaesthetics (GAs) and 16,709 regional anaesthetics (RAs). There were also 3,708 GAs and 17 RAs for procedures other than delivery. During this period there were 126 obstetrical admissions to the ICU. Sixteen were due to anaesthetic complications, twelve followed GA and four followed RA. Complications included anaphylaxis, high block and failure of tracheal intubation. The incidence of a major complication of a GA causing admission to the ICU was 1 in 932 and for RA was 1 in 4177 when these were given for delivery (P less than 0.01). If a complication requiring ICU admission and mechanical ventilation is used as the criterion of safety it appears that RA is safer than a GA for delivery. PMID- 1934225 TI - W. Easson Brown (1894-1957). PMID- 1934226 TI - Bilateral interpleural block for midline upper abdominal surgery. PMID- 1934227 TI - A nontraumatic induction technique for paediatric patients. PMID- 1934228 TI - Phaeochromocytoma presenting as MH. PMID- 1934229 TI - The laryngeal mask airway in children. PMID- 1934230 TI - Suction at the ready. PMID- 1934231 TI - Amiodarone and anaesthesia: concurrent therapy with ACE inhibitors--an additional cause for concern? PMID- 1934232 TI - M.O.U.T.H.S. PMID- 1934233 TI - Estimation and projection of adult AIDS cases: a simple epidemiological model. AB - Many HIV/AIDS (acquired immunodeficiency syndrome) models have been developed to help our understanding of the dynamics and interrelationships of the determinants of HIV (human immunodeficiency virus) spread and/or to develop reliable estimates of the eventual extent of such spread. These models range from very simple to very complex. WHO has developed a simple model for short-term projections of AIDS, details of which are presented here along with results obtained using the model to estimate and project AIDS cases for the USA, sub-Saharan Africa, and south/south-east Asia. WHO has also developed, based on the model described in this paper, a computer program (Epi Model), which will enable the user to easily change the values of any of the variables required by the WHO model. PMID- 1934234 TI - Strategies to improve immunization services in urban Africa. AB - The urban poor constitute a rapidly increasing proportion of the population in developing countries. Focusing attention on underserved urban slums and squatter settlements will contribute greatly to immunization programme goals, because these areas account for 30-50% of urban populations, usually provide low access to health services, carry a large burden of disease mortality, and act as sources of infection for the city and surrounding rural areas. Improvement of urban immunization programmes requires intersectorial collaboration, use of all opportunities to vaccinate eligible children and mothers, identification of low coverage neighbourhoods and execution of extra activities in these neighbourhoods, and community mobilization to identify and refer persons for vaccination. Improved disease surveillance helps to identify high-risk populations and document programme impact. New developments in vaccines, such as the high-dose Edmonston-Zagreb vaccine, will allow changes in the immunization schedule that facilitate the control of specific diseases. Finally, operational research can assist managers to conduct urban situation assessments, evaluate programme performance at the "micro" level, and design and monitor interventions. PMID- 1934235 TI - Duration of immunity following immunization with live measles vaccine: 15 years of observation in Zhejiang Province, China. AB - The duration of immunity following measles vaccination of 2882 immunized children has been investigated in a closed region of China for 15 years. A total of 1002 of the children were treated as primary immunization subjects, and 1547 as reimmunization subjects. These two cohorts were not in contact with known wild measles virus over the whole observation period, and the results obtained probably reflected the antibody responses to measles vaccine alone. The remaining 333 vaccinees came into contact with wild measles virus, and this permitted evaluation of the protective effect of the measles vaccines tested: 4 children experienced very mild clinical measles, and 329 experienced subclinical infection, including 12 who had had undetectable haemagglutination-inhibition antibodies for 9-10 years. These results indicate that the immunity induced by successful primary immunization may persist for at least 15 years. Within this period, a second dose of vaccine only induces low antibody responses which decrease rapidly to their original levels. This provides strong evidence that the immunity produced by primary immunization is long-lasting. However, there were some indications that reimmunization might produce better effects if live attenuated measles virus were used with a longer interval between doses. PMID- 1934236 TI - Case-control evaluation of a school-age BCG vaccination programme in subtropical Australia. AB - In 1956 a programme was initiated to vaccinate all children aged 12-14 years who were attending schools in Queensland, Australia. In view of the declining incidence of tuberculosis in Australia as a whole, there was a need to evaluate the effectiveness of the programme and its procedures. We therefore carried out a case-control study of Queensland's population, excluding certain known high-risk groups. Cases were Queensland residents with notified tuberculosis and of the appropriate age; two controls per case were chosen from the electoral roll. Information on vaccination status was obtained mainly from questionnaires and school records, where available. The results show that at best BCG vaccination had a modest protective effect, approximately 30% when the patients were diagnosed, which was on average 15 years after they had been vaccinated in the school programme. In the north the climate of Queensland is tropical, while in the more heavily populated south it is subtropical. A substantial proportion of the school records reported weak positive reactions to preliminary tuberculin testing, believed to be due largely to atypical mycobacteria. A similar phenomenon has been observed in other tropical regions, and may help to explain the apparent absence of a strongly protective effect for BCG vaccination. PMID- 1934237 TI - Levels and risk factors for perinatal mortality in Ahmedabad, India. AB - To estimate levels and determinants of perinatal mortality, we conducted a hospital-based surveillance and case-control study, linked with a population survey, in Ahmedabad, India. The perinatal mortality rate was 79.0 per 1000, and was highest for preterm low-birth-weight babies. The case-control study of 451 stillbirths, 160 early neonatal deaths and 1465 controls showed that poor maternal nutritional status, absence of antenatal care, and complications during labour were independently associated with substantially increased risks of perinatal death. Multivariate analyses indicate that socioeconomic factors largely operate through these proximate factors and do not have an independent effect. Estimates of attributable risk derived from the prevalence of exposures in the population survey suggest that improvements in maternal nutrition and antenatal and intrapartum care could result in marked reductions of perinatal mortality. PMID- 1934239 TI - [Control of human African trypanosomiasis in Luba in equatorial Guinea:evaluation of three methods]. AB - The object of this study was to (a) reduce the prevalence of sleeping sickness by serological testing, parasitological examination, and treatment of every infected person; (b) determine the maximum acceptable interval between serological surveys; and (c) define the impact of vector control, using monopyramidal non impregnated traps, on the transmission. For this sero-parasitological survey, the focus in Luba was divided into three zones as follows: Epicentre A (with high prevalence, 27.5%), Epicentre B (with average prevalence, 8.3%), and Peripheral C (with moderate prevalence, 3.0%). Differences in the prevalence rates in the Epicentres and Peripheral zone permitted the use of three different approaches for control and epidemiological follow-up of the disease: (1) Serological examination of the entire population was carried out by the indirect immunofluorescent antibody test (IFAT), with six-month intervals in Epicentres A and B and once a year in the Peripheral zone C. (2) DIAGNOSIS AND TREATMENT: all IFAT seropositives were examined in Luba hospital for parasites, and every parasitologically confirmed patient was treated according to the WHO protocol of 1983. Another serological test (CATT) was applied to cases in which trypanosomes were not present and if this was positive, the CSF was examined. Cases with parasites and abnormal CSF were treated with melarsoprol, and those with a normal CSF received pentamidine. CATT-negative and parasite-negative cases were considered to be false-positives by IFAT and free of the disease. (3) Vector control: 74 monopyramidal traps (18 traps per km2) were set up in Epicentre A. The flies captured were collected once a month and sent to the programme's laboratory where they were identified and counted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934238 TI - [Control of onchocerciasis with ivermectin: results of a mass campaign in northern Cameroon]. AB - A mass chemotherapy campaign to treat onchocerciasis with ivermectin was carried out in northern Cameroon, in the North Vina valley, a savanna area that is part of the extended Vina-Pende-Longone focus. More than 20,000 people aged five years and over were treated at least once and more than 30,000 treatments were distributed. One to four treatments were given at intervals of six months or one year. Clinical and parasitological examinations of representative samples of the treated population and full ophthalmological examinations of males aged 15 to 35 years were carried out before each treatment to assess the efficacy of the different protocols of treatment. Secondary effects were recorded daily during the week after administration of ivermectin in the whole population treated. The evolution of arterial blood pressure was monitored over seven days in about 300 adults living in the hyperendemic region. The impact of mass treatment on natural transmission of the disease was evaluated by daily capture and dissection of blackflies during the month before and the two months after treatment. All levels of onchocerciasis endemicity were represented in the study area (maximum community microfilarial load (CMFL), 300 microfilariae per biopsy). Six months and one year after the first treatment, loads were down by more than 90% and more than 60% respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934240 TI - Susceptibility of Plasmodium falciparum to different doses of quinine in vivo and to quinine and quinidine in vitro in relation to chloroquine in Liberia. AB - Chloroquine-resistant Plasmodium falciparum has been spreading rapidly after its emergence in 1988 in Yekepa. The in vivo and in vitro susceptibilities to quinine and quinidine, compared to chloroquine, were studied by investigating the number of treatment days required for radical cure and estimating the quinine concentrations concomitantly. The minimal inhibitory concentrations (MIC) for schizont maturation in all successful in vitro tests were 5.12 x 10(-6) mol/l for quinine and 1.28 x 10(-6) mol/l for quinidine, indicating that all 50 isolates were sensitive to the two drugs. The IC50 and IC90 values were 0.22 and 0.78 x 10(-6) mol/l for quinine and 0.07 and 0.26 x 10(-6) mol/l for quinidine, respectively. In vitro inhibition of parasites by 1.6 x 10(-6) mol/l of chloroquine was obtained in 31 out of 47 isolates, 16 (34%) being resistant. The IC50, IC90 and geometrical mean MIC for quinine were all about two times higher for the chloroquine-resistant than for the chloroquine-sensitive isolates (P = 0.006). P. falciparum infected children (n = 64) were randomly allocated to four groups and treated with quinine (10 mg/kg body weight twice daily) for 1 day (3 doses), 2, 4 and 7 days, respectively. All cleared their parasitaemias by day 4 but 5 out of 15 of those treated with only three doses showed a recurrence of parasitaemia between days 7 and 14; these were considered to be recrudescences. In the other groups, recurrent parasitaemias only occurred between days 17 and 28 and were considered to be reinfections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934241 TI - Economic analysis of several types of malaria clinics in Thailand. AB - The costs of three types of malaria clinics in Maesot District, north-west Thailand, for a one-year period in 1985-86 were compared from the institutional, community and social (institutional plus community) perspectives. The greatest number of patients at the lowest average institutional cost per smear and per positive case diagnosed (US$ 0.82) were seen at the large central clinic in Maesot town. The peripheral clinic in Popphra, a subdistrict town, had moderate institutional costs per smear and per positive case (US$ 1.58). The periodic mobile clinic, which served five villages on a fixed weekly schedule, had low average institutional costs per smear, but the highest cost per positive case (US$ 3.53). Community costs (those paid by patients and their families) were lowest in the periodic clinic. Addition of a periodic clinic to a system of central and peripheral clinics increased the number of malaria cases treated, particularly those involving women and under-16-year-olds. Although the periodic clinic entailed a modest increase in institutional costs, it minimized social costs. The results of the study suggest that use of a combination of central, peripheral, and periodic clinics, which maximizes access to malaria treatment, minimizes the social costs of malaria. PMID- 1934243 TI - Nomenclature for secreted regulatory proteins of the immune system (interleukins). WHO-IUIS Nomenclature Subcommittee on Interleukin Designation. AB - The recommended procedures and criteria for interleukin designations are described. The officially adopted designations are, in sequence, from interleukin 1 to interleukin-10, including interleukin-1 alpha and interleukin-1 beta. PMID- 1934242 TI - Monitored medico-surgical approach to the treatment of cystic hydatidosis. AB - Significant improvements in the health of patients with chronic multifocal abdominal hydatidosis, leading to recovery, have been observed after combined medico-surgical treatment. The benefits of massive surgical removal of cysts, accompanied by effective doses of albendazole, were assessed by the clinical, radiological, and immunological responses of individual patients. Variations in the levels of specific classes of immunoglobulins and circulating immunocomplexes provided additional measures of the state of host response and the persistence of parasitic activity. PMID- 1934244 TI - Plasma pharmacokinetics of the antitumour agents 5,6-dimethylxanthenone-4-acetic acid, xanthenone-4-acetic acid and flavone-8-acetic acid in mice. AB - Although the antitumour agent flavone-8-acetic acid (FAA) exhibits remarkable activity against murine solid tumours, its clinical use has a number of pharmacological drawbacks, including low dose potency and dose-dependent pharmacokinetics. Xanthenone-4-acetic acid (XAA) and its 5,6-dimethyl derivative (5,6-MeXAA) were synthesised during a search for better analogues of FAA. The maximal tolerated doses (MTDs) of 5,6-MeXAA, XAA and FAA in BDF1 mice were 99, 1,090 and 1,300 mumol/kg, respectively. At the MTD, 5,6-MeXAA displayed the following pharmacokinetic properties: maximal plasma concentration, 600 microM; mean residence time, 4.9 h; AUC, 2,400 mumol h 1-1; and volume of steady-state distribution, 0.2 l/kg. All compounds displayed nonlinear elimination kinetics at the MTD, but when the logarithm of the AUC was plotted against that of the delivered dose, the slope of the regression line for 5,6-MeXAA was found to be 1.2 as opposed to 1.4 for XAA and 1.98 for FAA. 5,6-MeXAA thus showed only a slight deviation from dose-independent kinetics. 5,6-MeXAA bound to plasma proteins in a manner similar to that exhibited by FAA, although the plasma concentration of free drug was lower for the former than for the latter. As a consequence, the calculated maximal free drug concentration for 5,6-MeXAA in plasma was 23 times lower than that for FAA. PMID- 1934245 TI - Haematological effects in mice of the antitumour agents xanthenone-4-acetic acid, 5,6-dimethyl-xanthenone-4-acetic acid [correction of 5,6-methyl-] and flavone acetic acid. AB - Treatment of C57Bl/6 x DBA/2 mice with the maximal tolerated dose of flavone-8 acetic acid (FAA, 1300 mumol/kg), xanthenone-4-acetic acid (XAA, 1090 mumol/kg), or its dose-potent derivative 5,6-dimethyl-xanthenone-4-acetic acid (5,6-MeXAA, 100 mumol/kg) resulted within 24 h in a dramatic reduction in the number of circulating lymphocytes, an elevation in haemoglobin concentrations and a reduction in platelet numbers. Neutrophil counts either remained unchanged or were slightly elevated. All three compounds caused a marked loss of cells in the thymus. Examination of histological sections of thymus at 48 h following treatment with XAA revealed a selective depletion of cortical thymocytes and no effects on the epithelium or other thymic structures. A transient decrease in cell numbers was seen in the spleen and femoral bone marrow, with recovery to normal levels occurring within 3 days. The number of haemopoietic stem cells, colony-forming units in culture (CFU-c), in the femoral bone marrow increased after drug administration despite the occurrence of a decrease in the overall number of cells in the femur. In contrast to the increase in CFU-c numbers seen in vivo, 2 h exposure of bone-marrow cells to FAA, XAA or 5,6-MeXAA in vitro resulted in a decrease in the surviving fraction of CFU-c. The results are consistent with the hypothesis that the in vivo haematological effects of these compounds are indirect, perhaps being mediated through the induction of cytokines, and contrast with the haematological effects of conventional antitumour agents. The biochemical and haematological effects are unlikely to be the cause of the acute toxicity observed for these compounds. PMID- 1934246 TI - Chemosensitivity and cytokine sensitivity of malignant mesothelioma. AB - Malignant mesothelioma arises in serosal tissues, is locally invasive, and is usually resistant to chemotherapeutic agents used clinically. To determine whether resistance to cytotoxic drugs was an inherent characteristic of mesothelioma cells, we performed in vitro chemosensitivity testing on five fully characterised human malignant mesothelioma cell lines and, for comparison, on three lines representative of clinically drug-resistant solid-tissue carcinomas using the MTT (tetrazolium bromide) assay system. Mesothelioma cell lines were intrinsically resistant to eight common antineoplastic drugs, with concentrations that produced a 50% reduction in optical density (IC50 values) for all drugs being equivalent, if not higher, for mesothelioma cell lines as compared with lung and colon carcinoma cell lines. We then investigated the direct anti mesothelioma activity of recombinant human cytokines with their antineoplastic properties. All five mesothelioma cell lines were resistant to tumour necrosis factor, but they displayed varying degrees of sensitivity to interferons (IFNs). IFN gamma directly inhibited the growth of two of five mesothelioma lines. IFN alpha displayed little activity against four of five mesothelioma lines. The mesothelioma cells that were sensitive to IFN alpha were resistant to IFN gamma, indicating that sensitivity to IFNs is not a genetic characteristic of malignant mesothelioma cells. Significant interactions between cytokines in combination were not observed. PMID- 1934247 TI - Iron- and ascorbic acid-induced lipid peroxidation in renal microsomes isolated from rats treated with platinum compounds. AB - Renal microsomes isolated on day 3 from cisplatin (CDDP, single i.p. injection, 4 or 6 mg/kg)-treated rats were monitored for their susceptibility to lipid peroxidation as compared with microsomes from rats treated with carboplatin (CBDCA, 30 mg/kg), transplatin (TDDP, 6 mg/kg) or CDDP hydrolysis products (4 or 6 mg/kg) or from control animals. Cephaloridine (1 g/kg daily for 4 days, i.p. injection) was used as a positive control. The effect of CDDP on renal microsomal glucose-6-phosphatase activity was investigated in vivo and in vitro. Following treatment with CDDP and CDDP hydrolysis products vs CBDCA and TDDP treatment, microsomes revealed an enhanced susceptibility to lipid peroxidation in a Fe2+ and/or ascorbic acid stimulation system. Increased lipid peroxidation, expressed as an increase in malondialdehyde (MDA) generation, paralleled the alterations in body and kidney weight and the elevations of plasma creatinine and blood urea nitrogen concentrations. Injection of the antioxidant N,N'-diphenyl-p phenylenediamine (DPPD, 0.5 g/kg, i.p.) at 24 h prior to CDDP treatment abolished the increased vulnerability of renal microsomes to lipid peroxidation. In vivo, only CDDP hydrolysis products exhibited a significant inhibitory effect on renal glucose-6-phosphatase activity. In vitro, rat renal and hepatic microsomal glucose-6-phosphatase activity was decreased by CDDP both time- and concentration dependently. Nephrotoxicity induced by CDDP and CDDP hydrolysis products might be attributable to iron-dependent lipid peroxidation and microsomes might represent target organelles on a subcellular level. PMID- 1934248 TI - Differential in vitro action of S-12363, a new vinblastine derivative, and of its epimer on microtubule proteins. AB - The action of two epimers of a new vinblastine derivative that differ in their in vivo antitumor activity and their cytotoxicity was studied in vitro in brain microtubule proteins. These two compounds, called S-12363 and S-12362, could not be distinguished from one another or from other active vinca alkaloids by their ability to prevent microtubule assembly. However, they differed strongly both from one another and from vincristine and vinblastine in their ability to induce the formation of tubulin paracrystals and in the stability of the paracrystals following temperature shifts from 0 degree to 37 degrees C and vice versa. The most potent drug, S-12363, induced considerable tubulin aggregation, which was even more pronounced than that observed in the presence of vincristine. Previous results have shown that S-12363, in contrast to vincristine, induces no neurotoxic effects. This observation is in disagreement with a direct relationship between tubulin aggregation and neurotoxicity. PMID- 1934249 TI - Urinary excretion of the enantiomers of ifosfamide and its inactive metabolites in children. AB - The precondition for the antineoplastic effect of ifosfamide (ifo) is the oxidation of the oxazaphosphorine ring system, which contains a chiral centre at the phosphorous atom. This "ring oxidation" leads to the formation of alkylating mustard via several steps. A second metabolic pathway produces the cytostatically inactive metabolites 2- and 3-dechloroethyl-ifosfamide (2-d- and 3-d-ifo). The urinary excretion of the optical isomers of unmetabolised ifo and of 2- and 3-d ifo, which represents the amount of ifo that has not been activated, was investigated by capillary gas chromatography for 18 treatment cycles in 14 children on various therapeutic schedules. The total cumulative excretion in 12 completely sampled cycles ranged from 27% to 50% of the ifo dose. Between 14% and 34% of the dose could be detected as ifo; 9% to 29%, as 3-d-ifo; and 2% to 8%, as 2-d-ifo. At 24 h after the end of therapy, excretion was nearly complete. Without exception, slightly more R-ifo (53%-61%) than S-ifo was excreted. S-2-d-ifo (50% 73%) was the main 2-d-metabolite. S-3-d-ifo (deriving from R-ifo) predominated in 6 of 14 children and R-3-d-ifo, in 8. Enantiomer-specific excretion increased after the end of infusion (up to 73% for R-ifo and 27% for S-ifo). We demonstrated stereospecific metabolism of ifo in children, with two different patterns of side-chain oxidation being observed. There was no evidence of important stereospecific ring oxidation in most children. A benefit should not be expected from the therapeutic application of pure enantiomers. PMID- 1934251 TI - Clinical pharmacokinetics of high-dose DTIC. AB - The pharmacokinetics of 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC, dacarbazine) given at a dose of 850-1,980 mg/m2 as a 10- to 30-min infusion was studied in cancer patients, and the plasma concentration-time curves were adjusted to a two-compartment model, with a mean t1/2 alpha value of 0.17 h (range, 0.1-0.26 h) and a mean t1/2 beta value of 2 h (range, 1.5-2.7 h) being found. The mean volume of the central compartment of (Vc) and the apparent volume of distribution (VB) were 0.42 1 kg-1 (range, 0.24-0.54 1 kg-1) and 1.49 1 kg-1 (range, 0.88-1.74 1 kg-1), respectively. The mean total body clearance of DTIC was 0.58 1 kg-1 h-1 (range, 0.26-0.82 1 kg-1 h-1), and the mean renal clearance was 0.28 1 kg-1 h-1 (range, 0.17-0.49 1 kg-1 h-1). Unchanged DTIC recovered from urine within 24 h varied from 11% to 63% of the delivered dose, with an inverse correlation being found between the DTIC dose and the amount excreted. The metabolite aminoimidazole carboxamide (AICA) was detectable in plasma from the start of DTIC infusion, and its concentration-time curve showed a monophasic decay, exhibiting a mean t1/2 value of 3.25 h (range, 1.77-5.82 h). Mean AICA renal clearance was 0.15 1 kg-1 h-1 (range, 0.05-0.32 1 kg-1 h-1). The amount of AICA excreted in urine increased with increasing DTIC dose and varied from 1.2% to 13.6% of the delivered DTIC dose. Both DTIC distribution and disposition and AICA production and renal excretion seemed to be limited after high DTIC doses as compared with the pharmacokinetics of low-dose DTIC. Nonlinear pharmacokinetics for high-dose DTIC could not be clearly excluded. PMID- 1934250 TI - A randomized study of epirubicin at four different dose levels in advanced breast cancer. Feasibility of myelotoxicity prediction through single blood-sample measurement. AB - Detailed pharmacokinetic analysis and subsequent evaluation of myelotoxicity were performed in 55 patients who had been randomized to 4 different doses of epirubicin (40, 60, 90 or 135 mg/m2 given i.v. every 3 weeks). A significantly positive correlation was demonstrated between the AUC and the myelotoxicity of epirubicin. A similar correlation was observed when the metabolite epirubicinol was also considered. The decrease in leucocyte count as expressed by the logarithmic ratio between nadir WBC and initial WBC was linearly correlated with the AUC of either epirubicin alone (r = -0.55, P less than 0.001) or epirubicin and epirubicinol together (r = -0.63, P less than 0.001). As a relationship between the concentration of epirubicin in a single plasma sample taken at 6 h following i.v. administration and the AUC of the drug has been established, a log linear relationship between the expected decrease in leucocytes and the concentration at 6 h after administration could be calculated. The proposed model is expressed as the equation: log WBCnadir = log WBCinitial -0.0073 x c6 (ng/ml) 0.14. PMID- 1934252 TI - Mitoxantrone and cytarabine versus daunorubicin and cytarabine in previously untreated patients with acute myeloid leukemia. AB - A total of 44 adults aged 18-78 years were allocated to an open randomized study whose aim was to compare the efficacy and toxicity of mitoxantrone with those of daunorubicin in previously untreated patients presenting with acute myeloid leukemia. In one arm, induction treatment consisted of mitoxantrone plus cytarabine given on a 3- plus 7-day schedule. Post-induction treatment consisted of two courses of mitoxantrone plus cytarabine given on a 2- plus 5-day schedule. In the control arm, mitoxantrone was replaced by daunorubicin. In all, 14 of 21 eligible and evaluable patients in the mitoxantrone arm achieved a complete remission (CR). In the control arm, 14 of 20 subjects attained a CR. The median survival was 365 days for patients randomized to mitoxantrone-cytarabine and 401 days for those given daunorubicin-cytarabine. The efficacy and toxicity of mitoxantrone were similar to those of daunorubicin. PMID- 1934253 TI - Modulation of cytosine arabinoside-induced proliferation inhibition by exogenous adenosylmethionine. AB - The effect of cytosine arabinoside on adenosylmethionine synthesis in relation to its proliferation-inhibiting ability was investigated in HT/29 and SW 620 human colon-tumor cell lines. A significant decrease in adenosylmethionine synthetase (E. C.2.4.2.13) activity was found after 2.5 h incubation with the drug, suggesting that depletion of adenosylmethionine pools might occur. Both this possible loss of adenosylmethionine and the cytostatic effect of cytosine arabinoside could partly be reversed by the exogenous administration of the former drug. Our data show that the cytostatic effect of cytosine arabinoside may be due in part to a shortage of adenosylmethionine; this finding is important for the design of combination chemotherapy regimens. PMID- 1934254 TI - High-dose ara-C and etoposide in refractory or relapsing acute leukemia. AB - A total of 32 patients (15 men and 17 women) presenting with relapsing or refractory acute leukemia were treated with a 3-h infusion of 3 g/m2 cytosine arabinoside (ara-C) twice daily on days 1-6 and a 1-h infusion of 100 mg/m2 etoposide on days 1-5. In all, 6 subjects had acute lymphocytic leukemia (ALL); 25 had acute myeloid leukemia (AML) of types M1 (n = 6), M2 (n = 10), M4 (n = 5), and M5 (n = 4); and 1 had mixed-type leukemia. The median age was 35 years (ranges, 16-62 years). Of the patients presenting with AML, 11 were primarily refractory and 3 became refractory after their first relapse. Six subjects had an early first relapse following a complete remission (CR) that lasted less than 6 months and five, a second relapse. Another patient underwent a primary relapse after greater than 6 months but had been heavily pretreated. In all, 5 subjects with refractory AML achieved a CR (36%; 95% confidence interval (CI), 10%-62%) as did 7 patients exhibiting relapsing AML (58%; CI, 30%-86%). Three patients who had relapsing or resistant ALL achieved a CR. Side effects consisted of severe hematotoxicity associated with granulocytopenia of less than 500/mm3 that lasted for a mean of 23.6 days and thrombocytopenia of less than 20,000/mm3 whose mean duration was 20.8 days. Marked gastrointestinal toxicity and infections were also prevalent. Cutaneous and ocular toxicity as well as allergic, pulmonary and cerebellar side effects were observed in a few cases. We conclude that the combination of high-dose ara-C and etoposide is a powerful but toxic induction regimen for refractory or relapsed acute leukemia. PMID- 1934255 TI - Carcinogenic properties of pharmaceutical agents evaluated in the IARC Monographs programme. AB - Almost 200 pharmaceutical chemicals and groups of drugs have been evaluated for their carcinogenic properties by working groups convened by the International Agency for the Research on Cancer. Therapeutic agents are exceptional environmental carcinogens in that humans are exposed to relatively pure substances at well-defined dosages. Of those evaluated, 20 are conclusively carcinogenic to humans and 52 are probably or possibly carcinogenic. The human tissues most often affected are bone marrow, skin, urinary bladder, liver, lymphatic tissue and endometrium. In cases in which there is sufficient evidence for carcinogenicity from both epidemiological and experimental studies, the similarity between humans and animals with regard to the target organs involved is close (85%). Since data on carcinogenicity exist for several groups of pharmaceuticals, risk versus benefit evaluations should be made carefully in relation to possible clinical applications. PMID- 1934256 TI - Effects of butylated hydroxyanisole pretreatment on low dose N-methyl-N'-nitro-N nitrosoguanidine- or N,N-dibutylnitrosamine-induced rat forestomach or esophageal carcinogenesis. AB - The effects of butylated hydroxyanisole (BHA) pretreatment on subsequent low dose N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N,N-dibutylnitrosamine (DBN) treatment on forestomach or esophageal carcinogenesis were investigated in male F344 rats. Groups of animals were pretreated with 2% BHA or basal diet alone for 24 weeks and then were given 20 mg/kg body wt MNNG once every 2 weeks, 0.025% DBN in drinking water continuously or basal diet alone for the subsequent 24 weeks. Further groups of rats were similarly treated with BHA or basal diet alone for 24 weeks, placed on basal diet for the next 24 weeks and then treated with MNNG, DBN or basal diet alone for the subsequent 24 weeks. Animals were killed 48 or 72 weeks after the beginning of the experiment. Histopathological examination showed that the incidence of forestomach tumors was not significantly affected by the BHA pretreatment in the MNNG-treated groups. On the other hand, the incidence of esophageal squamous cell carcinomas was lower in the group pretreated with BHA followed by DBN than in that treated with basal diet followed by DBN (48 week experiment). There was no significant difference in esophageal tumor incidence in the 72 week experiment. The results thus indicate that continuous treatment with 2% BHA for 24 weeks does not exert initiating activity on forestomach and esophageal epithelia. PMID- 1934257 TI - Specific gain of chromosome 19 in preneoplastic mouse liver cells after diethylnitrosamine treatment. AB - Most attempts to elucidate primary cytogenetic events have been made on the basis of chromosome analysis of cells from the later stages of tumor development. Hence it is difficult to decide which, if any, of the observed chromosomal alterations are causative rather than consequential in neoplastic development. One approach to understand the role of chromosomal changes in neoplasia is to examine the chromosomal constitution of cells at early stages in the process of carcinogenesis. We have developed a method for direct preparation of metaphase plates of cells from preneoplastic liver nodules and we present herein the first report of nonrandom chromosome changes in solid tumor precursor cells. The results of the cytogenetic analysis demonstrated trisomies/polysomies for chromosome 11 and chromosome 19. A specific increase in the number of chromosome 19 was found in 43% of the 37 plates karyotyped and 25% of the plates demonstrated increase in the number of chromosome 11. The finding shows that gross chromosomal changes such as polysomies may play an important role in the early development of tumors. They further indicate the presence of a gene on chromosome 19 with an essential role either in the initiation or promotion of the neoplastic transformation of hepatocytes. PMID- 1934259 TI - Cellular levels of O6-methylguanine-DNA methyltransferase in mammary epithelial cells and liver from virgin, pregnant and pituitary grafted mice. AB - O6-Methylguanine-DNA methyltransferase (O6-MT) is a DNA repair protein that reverses alkylation damage at the O6 position of guanine. In the process, O6-MT undergoes suicide inactivation. To determine if this enzyme might be regulated by pregnancy-associated hormones we measured changes in the level of O6-MT in isolated mouse mammary epithelial cell homogenates during different reproductive states. These were pregnancy, ectopic pituitary transplantation, proestrus/estrus and diestrus. O6-MT levels were found to be similar in mice in proestrus/estrus (0.95 fmol/micrograms DNA) as compared to diestrus (0.94 fmol/micrograms DNA) and also mixed populations of virgin mice (1.09 fmol/micrograms DNA). A mean for all virgin mice (0.97 fmol/micrograms DNA) was used as a comparative index. O6-MT decreased 2-fold during pregnancy in mammary epithelial cells to a mean value of 0.45 fmol/micrograms DNA (P less than 0.05). A smaller decrease (0.65 fmol/micrograms DNA; P less than 0.01) in mammary epithelial cells was found at 3 weeks following pituitary isograft. The repair capacity of mammary epithelial cells to liver was compared by measurements made in liver homogenates from the same mice and are approximately 3-fold higher in liver from virgin mice (3.2 fmol/micrograms DNA) than mammary gland. Liver levels of O6-MT increased in pregnant (5.3 fmol/micrograms DNA) and pituitary transplanted (3.9 fmol/micrograms DNA) mice, and were 5- and 4-fold higher than the concentration in virgin mammary epithelial cells respectively. PMID- 1934258 TI - The effect of diacylglycerols on fibronectin release and its reversal by retinoic acid in cell culture. AB - Previous work from our laboratory showed that tumor promoters such as phorbol ester (TPA) stimulated the release of fibronectin (FN) from the surface of several cell types in culture, and that this stimulation was counteracted by retinoic acid. Diacylglycerols (DAGs) are the endogenous ligands of the TPA receptor and can activate and translocate protein kinase C (PKC) in a manner similar to TPA. To show that the release of FN is related to activation of PKC, we tested the action of DAGs on FN release from human lung fibroblasts and its counteraction by retinoic acid. We found that DAGs stimulated the release of FN in a concentration- and time-dependent manner. The stimulation of the release of FN correlated with the translocation-activation of PKC by DAG. Retinoic acid reversed the action of DAG with respect to stimulation of FN release and inhibited this release even in the absence of DAG. These results suggest that the release of FN is in some way related to translocation-activation of PKC. PMID- 1934260 TI - Induction of transformation in NIH3T3 cells by moderate growth constraint: evidence that neoplasia is driven by adaptational change. AB - The NIH3T3 cell line undergoes transformation when the cells are maintained at high densities for extended periods. In an effort to define the physiological status of the cells before and during the transformation process, they were seeded in medium containing 2, 5 or 10% calf serum (CS) and growth was monitored by measurements of cell numbers and by incorporation of [3H]thymidine into DNA. Transformed foci began to appear by 7 days in 2% CS, at least 3 days after the onset of density-dependent growth inhibition, and by 10 days in 5% CS, 6 days after the onset of growth inhibition. The rate of DNA synthesis in both serum concentrations had declined by 7 days to less than 1/15th of the initial rate measured by day 2. Transformation did not occur in cells exposed to 10% CS which, though supporting even higher saturation densities, underwent a 100-fold decline in DNA synthesis after reaching confluence. Transfer and regrowth in 2% CS of cells from all three serum concentration revealed a steep increase in capacity for focus formation of cells previously cultured in 2 and 5% CS after they had reached confluence, but no such increase in cells previously cultured in 10% CS, indicating that the lack of foci in the original 10% CS incubation was due to suppression of transformation and not to masking of foci at very high cell densities. Determination of the fraction of dividing cells by [3H]thymidine autoradiography showed a similar decline prior to the appearance of transformed cells in 2% CS. In addition, a reactivation of mitosis in non-focal cells occurred by day 24, indicating that a much higher proportion of cells escaped the moderate growth constraint than might have been expected by the total number of foci formed on transfer. Our results are consistent with the premise that transformation is an adaptive response to moderate growth constraints, but not with a mutational origin. PMID- 1934261 TI - Suppression of aflatoxin B1-induced hepatotoxic lesions by crocetin (a natural carotenoid). AB - The suppressive effects of crocetin (a natural carotenoid) on the hepatotoxic lesions induced by aflatoxin B1 (AFB1) were investigated in male Wistar rats. Rats were divided into five groups: groups I and II served as normal and solvent control respectively. Group III was given AFB1 (25 micrograms/day/rat) alone; group IV was given crocetin (0.1 mg/day/rat) alone; and group V received both AFB1 and crocetin. Rats received AFB1 and crocetin for 9 and 10 weeks respectively, and were maintained on basal diet for 35 weeks. At the end of the experiment (week 45), the incidence of liver lesions in rats of group V was significantly reduced by approximately 40% compared with group III. There were no liver lesions in rats of groups I, II and IV. A significant protective effect of crocetin on AFB1 hepatotoxicity was shown, as manifested by reduced effects on the activities of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase (P less than 0.01-0.001). From our previous results and present data, we suggest that the suppression of crocetin on AFB1 hepatotoxicity in the rats might be due to the defense mechanisms of hepatic tissues that elevated the GSH S-transferase activity and decreased the formation of hepatic AFB1-DNA adducts. PMID- 1934262 TI - Role of solubilized chromium in the induction of morphological transformation of Syrian hamster embryo (SHE) cells by particulate chromium(VI) compounds. AB - Chromium(VI) compounds--Ca, Sr, Zn and Pb chromates--were studied for cytotoxicity and morphological transformation in Syrian hamster embryo (SHE) cells in relation to their solubilization in cell culture conditions and intracellular Cr concentration. Ca, Sr and Zn chromates were completely solubilized after 1 day of incubation in cell cultures; for Pb chromate, 20-36% Cr was solubilized only after 7 days. In two parallel transformation assays, the SHE cells were treated with suspensions or with corresponding supernatants (containing only solubilized Cr) of these compounds. A statistically significant relationship was observed between the Cr treatment concentration and the amount of Cr per cell, irrespective of the compound (except suspensions of Pb chromate). The cytotoxicity was due to extracellular solubilized chromium because treatments with either supernatants or suspensions of Ca, Sr and Zn chromates gave the same LC50 of 0.31 +/- 0.01 microgram Cr/ml. A clear dose-response relationship was observed for the induction of morphological transformation for each compound, either previously solubilized or in suspension. The expression of the transformation frequencies as a function of the Cr concentration/cell revealed that (i) the transformation frequency is dependent on the Cr concentration/cell irrespective of the Cr compound Ca, Sr or Zn chromate, (ii) the transformation frequency induced by solubilized Pb chromate is higher than that induced by the other compounds at the same concentration of Cr/cell. A double treatment with solutions of Cr and Pb at corresponding concentrations induced the same transformation frequency as the solubilized Pb chromate. The results show that the solubilization of particulate Cr(VI) compounds is a critical step for their cytotoxic and transforming activities; the intracellular soluble Cr is the sole causative agent of the transforming activity of Ca, Sr and Zn chromates, while Pb appears to act synergistically with Cr in inducing the transformation by Pb chromate. PMID- 1934263 TI - Inhibitory effects of beta-carotene on preneoplastic lesions induced in Wistar rats by the resistant hepatocyte model. AB - The inhibitory effects of beta-carotene (BC) on preneoplastic lesions induced in male Wistar rats by the resistant hepatocyte model was investigated. Rats were divided into six groups. Initiation was performed in all animals by a single injection of diethylnitrosamine. During the selection/promotion period five doses of 2-acetylaminofluorene were administered to the rats and a partial hepatectomy was performed. To three different groups BC was given by gavage throughout the experiment, before the initiation or during the selection/promotion period respectively. Three other groups served as controls and received corn oil instead of the carotenoid. At the end of the study (8 weeks), BC administration throughout the experiment reduced the incidence (P less than 0.005), multiplicity as well as the total number and size of hepatocyte nodules. Furthermore, it significantly decreased the number of foci per cm2 (P less than 0.05), the average focal area (P less than 0.01) and the percentage of liver parenchyma occupied (P less than 0.01). Similar results were observed when BC was given only before the initiation. However, the administration of the carotenoid during the selection/promotion period did not result in significant decreases of these parameters. These results suggest that the inhibitory effects of BC are primarily exerted on the initiation phase of the hepatocarcinogenic process. Nevertheless, continuous long-term exposure to the carotenoid would confer a greater degree of protection. In addition, by means of an analysis of correlation a positive relationship was found between the number of hepatocyte nodules and the hepatic concentration of BC. In contrast, an inverse relationship was observed between the number of nodules and the hepatic concentration of total vitamin A. PMID- 1934264 TI - Immunocytochemical localization of DNA adducts induced by a single dose of N nitroso-N-methylbenzylamine in target and non-target tissues of tumor formation in the rat. AB - The formation and short-term persistence of O6-methylguanine (O6-meGua) and 7 methylguanine (7-meGua) in individual cells of various target and non-target tissues for tumor induction in rats were examined after a single dose of N nitroso-N-methylbenzylamine (NMBzA). In the principal target organ, the esophagus, both adducts were observed at 6 h after 0.5, 1.0 and 2.5 mg NMBzA/kg in a dose-dependent manner in nuclei of epithelial cells only. Nuclear staining in this organ had apparently declined by 72 h and modified nuclei were found in the more differentiated cells located closer to the lumen. In epithelial cells of the tongue, another target organ of NMBzA, methylation at 6 h was also dose dependent. At 72 h nuclear staining was lower and again largely located in differentiated cells. In the liver, a non-target organ, O6-meGua was not detectable and 7-meGua-specific staining was weak, being only observed at 6 h after the highest dose. Dose-dependent DNA methylation was seen, both at 6 and 72 h, in other non-target organs such as lung (bronchiolar epithelial cells), trachea (epithelial and glandular cells) and nasal cavity (respiratory epithelial cells, ductal cells of the respiratory lamina propria and cells of Bowman glands of the olfactory lamina propria); the nuclei of the glandular cells were highly methylated. Visual inspection of lung, trachea and nasal cavity indicated no or only minor losses of O6-meGua and 7-meGua between 6 and 72 h. Microdensitometric determination of the nuclear staining at 6 and 72 h indicated that the promutagenic O6-meGua was partially lost from cells of the tongue epithelium but did persist in esophageal epithelial cells; 7-meGua was lost to a substantial extent from both tongue and esophagus. The present results imply that the organotropism of NMBzA is not uniquely determined either by the initial level or the short-term persistence of DNA methylation. PMID- 1934265 TI - Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon. AB - The metabolic activation of the food-borne rodent carcinogens 2-amino-3 methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-6 methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) was compared with that of the known human carcinogen 4-aminobiphenyl (ABP), using human liver microsomes, human and rat liver cytosols, and human colon cytosol. All of these aromatic amines were readily activated by N-hydroxylation with human liver microsomes (2.3-5.3 nmol/min/mg protein), with PhIP and ABP exhibiting the highest rates of cytochrome P450IA2-dependent N-oxidation, followed by MeIQx, IQ and Glu-P-1. In contrast, while ABP and 2-aminofluorene were readily N-acetylated (1.7-2.3 nmol/min/mg protein) by the polymorphic human liver cytosolic N acetyltransferase, none of the heterocyclic amines were detectable as substrates (less than 0.05 nmol/min/mg protein). Likewise, only low activity was observed (0.11 nmol/min/mg protein) for the N-acetylation of p-aminobenzoic acid, a selective substrate for the human monomorphic liver N-acetyltransferase. The radiolabeled N-hydroxy (N-OH) arylamine metabolites were synthesized and their reactivity with DNA was examined. Each derivative bound covalently with DNA at neutral pH (7.0), with highest levels of binding observed for N-OH-IQ and N-OH PhIP. Incubation at acidic pH (5.0) resulted in increased levels of DNA binding, suggesting formation of reactive arylnitrenium ion intermediates. These N-OH arylamines were further activated to DNA-bound products by human hepatic O acetyltransferase. Acetyl coenzyme A (AcCoA)-dependent, cytosol-catalyzed DNA binding was greatest for N-OH-ABP and N-OH-Glu-P-1, followed by N-OH-PhIP, N-OH MeIQx and N-OH-IQ; and both rapid and slow acetylator phenotypes were apparent. Rat liver cytosol also catalyzed AcCoA-dependent DNA binding of the N-OH arylamines; and substrate specificities were comparable to human liver, except that N-OH-MeIQx and N-OH-PhIP gave relatively higher and lower activities respectively. Human colon cytosols likewise displayed AcCoA-dependent DNA binding activity for the N-OH substrates. Metabolic activity was generally lower than that found with the rapid acetylator liver cytosols; however, substrate specificity was variable and phenotypic differences in colon O-acetyltransferase activity could not be readily discerned. This may be due, at least in part, to the varied contribution of the monomorphic acetyltransferase, which would be expected to participate in the enzymatic acetylation of some of these N-OH arylamines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1934266 TI - The effect of dose and cytochrome P450 induction on the metabolism and disposition of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx) in the rat. AB - The effect of dose and cytochrome P450 induction on the metabolism and disposition of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline (MeIQx) was investigated in the male Sprague-Dawley rat. Animals were given MeIQx by gavage at doses of 0.01, 0.2 or 20 mg/kg body wt. The phase II conjugates, MeIQx-N2 sulfamate and MeIQx-N2 glucuronide were the predominant metabolites found in urine of non-induced animals at the highest dose treatment. Animals induced with polychlorinated-biphenyl (PCB) produced greater amounts of metabolites hydroxylated at the 5 position of MeIQx which were excreted as glucuronide or sulfate conjugates. At the lowest dose studied, the urinary excretion profile was nearly identical for both animal groups and cytochrome P450 induction had little influence on metabolism. In contrast to high dose exposure, where sulfamate formation was a major route of detoxification, N2 glucuronide formation was the most important metabolic pathway for elimination of MeIQx at low doses. Liver microsomes transformed MeIQx to the genotoxic metabolite 2 hydroxyamino-3,8-dimethylimidazo[4,5-f]quinoxaline (HNOH-MeIQx) and N-hydroxylase activity was 20-fold greater in microsomes obtained from PCB-treated animals than in untreated control animals. The increase in N-hydroxylase activity was discerned in vivo through formation of the metastable N-glucuronide conjugate of HNOH-MeIQx (MeIQx-[HO-N]-Gl). This metabolite accounted for approximately 3% of the dose in bile of PCB-treated rats. In contrast, in the non-induced rat, MeIQx [HO-N]-Gl was preferentially excreted in urine and accounted for approximately 0.2-1% of the total dose. These results demonstrate that the metabolism of MeIQx in the rat is influenced by both dose and cytochrome P450 induction. The absence of intestinal tumors in the non-induced rat may be partially attributed to the low levels of formation and poor biliary excretion of the N-glucuronide conjugate of the genotoxic metabolite HNOH-MeIQx. PMID- 1934267 TI - No promotion of urinary bladder carcinogenesis by sodium L-ascorbate in male ODS/Shi-od/od rats lacking L-ascorbic acid-synthesizing ability. AB - The promoting effects of sodium L-ascorbate (Na-AsA) on two-stage urinary bladder carcinogenesis were investigated in male ODS/Shi-od/od rats. This strain genetically lacks L-ascorbic acid-synthesizing ability, which is controlled by a single autosomal recessive od gene; heterozygous ODS/Shi(-)+/od, normal ODS/Shi( )+/+ or F344 rats are able to synthesize L-ascorbic acid. In experiment 1, ODS/Shi-od/od and F344 rats were given 0.05% N-butyl-N-(4 hydroxybutyl)nitrosamine (BBN) in their drinking water for 2 weeks and then basal CA-1 diet with or without 5% Na-AsA for 32 weeks. F344 rats were sensitive to the promoting effects of Na-AsA, whereas ODS/Shi-od/od rats were resistant. Administration of Na-AsA increased the urinary pH and the urinary concentrations of Na+ and total ascorbic acid in all strains. In experiment 2, DNA synthesis in the urinary bladder epithelium of F344 rats fed MF diet or CA-1 diet was increased by exposure to 5% Na-AsA for 8 weeks, but not in ODS/Shi-od/od rats fed CA-1 diet. In experiment 3, ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were given 0.05% BBN for 4 weeks and then CA-1 diet with or without 5% Na-AsA for 32 weeks. ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were resistant to the promoting effects of Na-AsA in two-stage urinary bladder carcinogenesis. The urinary pH and the urinary concentrations of Na+ and total ascorbic acid in ODS/Shi-od/od, ODS/Shi(-)+/od and ODS/Shi(-)+/+ rats were increased by the administration of Na-AsA. These results indicate that ODS/Shi-od/od rats are resistant to the promoting effects of Na-AsA in two-stage urinary bladder carcinogenesis, and that the susceptibilities of ODS/Shi-od/od rats are regulated by genes different from the gene at the od locus. PMID- 1934268 TI - Comparison of ras activation during epidermal carcinogenesis in vitro and in vivo. AB - Mouse epidermal cells have frequently been used to study the role of ras oncogenes in transformation in vivo and in vitro. After initiation with dimethylbenzanthracene (DMBA) in vivo, greater than 90% of the papillomas arising show the same A:T----T:A transversion at codon 61 of the H-ras gene, presumed to be the initiating event. On the other hand, initiation of epidermal cells in culture with carcinogens, followed by selection of initiated cells by resistance to calcium-induced differentiation, does not in general lead to the isolation of clones carrying mutant ras genes. Some other aspects of tumour progression in vivo can be reproduced using epidermal cells in culture: a rare DMBA transformant carrying the codon 61 mutation and expressing a 2:1 ratio of normal to mutant ras alleles gave rise upon transplantation to a more aggressive line in which the ratio of normal to mutant H-ras genes (and p21 products) was reversed. Similar alterations in ras gene dosage have been seen during progression of papillomas to carcinomas in vivo. We conclude that the mechanisms of initiation in vitro may differ substantially from in vivo, and depend on the particular culture conditions used. Moreover, the effects of mutant H-ras expression in mouse epidermal cells are variable depending on the genetic background of the cell. PMID- 1934270 TI - Acetylation of 2-aminofluorene derivatives by dog hepatic microsomes. AB - Dog urinary bladder is a target organ of carcinogenic arylamines. However, dog hepatic and urothelial cytosols lack acetylation enzymes that are capable of activating N-hydroxy metabolites of arylamines, suggesting that other enzymes may be involved. In the present study, we found that dog liver microsomes were capable of N-acetylation of 2-aminofluorene and N,O-acetyltransfer of N-hydroxy-2 acetylaminofluorene (N-OH-AAF), and that these activities were inhibited by paraoxon. The 0.25% Triton X-100 extractable fraction of microsomes was resolved on an ion-exchange column into three different proteins that retained these activities. Two of these proteins, designated as enzyme I and enzyme II, were further chromatographed on a Sephacryl S-300 column. As judged from the gel filtration profile, the mol. wt of enzyme I was approximately 180 kDa and that of enzyme II was greater than 700 kDa. SDS-PAGE analysis showed that the subunit weight of enzyme II was approximately 150 kDa. In addition to N-acetylation of 2 aminofluorene and N,O-acetyltransfer of N-OH-AAF, these three enzymes were capable of the deacetylation of 2-acetylaminofluorene, N-OH-AAF and 4-nitrophenyl acetate. The ability of these microsomal enzymes to activate N-hydroxylated aromatic amines and the presence of these enzymes in urothelial cells, reported previously, suggests that they may play an etiological role in the carcinogenicity of these agents in the dog. PMID- 1934269 TI - Quantitative structure-activity studies on indole alkaloid tumor promoter indolactam congeners. AB - Nine indolactam congeners with L-Abu, gamma,delta-delta-Nva, Nva, Phg, tert-Leu, Leu, Ile, allo-Ile, Nle, instead of L-Val in (--)-indolactam-Val, were synthesized by microbial conversion and examined using two biological tests related to tumor promotion. The tests were inhibition of the specific binding of [3H]12-O-tetradecanoylphorbol-13-acetate (TPA) to the mouse epidermal particulate fraction, and stimulation of radioactive inorganic phosphate incorporation into phospholipids of HeLa cells. These two biological activities correlated well for each derivative. (--)-Indolactam-Ile with L-Ile in place of L-Val in (--) indolactam-Val, which we have recently confirmed to occur naturally, was the most active of the ten indolactam congeners tested, suggesting that (--)-indolactam Ile is a more potent tumor promoter than (--)-indolactam-Val in vivo. The effects of the substituents at position 12 on the TPA receptor binding were analyzed quantitatively using physicochemical substituent parameters and regression analysis. The results indicated that both hydrophobicity and bulkiness of the substituents at position 12 increased the binding ability to the TPA receptor, supporting the recent hypothesis that the isopropyl group at position 12 of (--) indolactam-Val is involved in the hydrophobic interaction on the receptor site. PMID- 1934271 TI - Site specificity of N-methyl-N-nitrosourea-induced transition mutations in the hprt gene. AB - The reaction product of N-methyl-N-nitrosourea (MNU) with DNA, O6-methylguanine (O6-MeG), is responsible for the mutagenic and carcinogenic effects of this carcinogen. These involve activation of the H-ras proto-oncogene in rat mammary tumors by MNU, with a high frequency of GC to AT transitions in codon 12 of this gene. The present study aimed to investigate the types and position specificities of mutations induced by MNU in another gene, the hprt gene of V79 Chinese hamster cells. Furthermore, since processes involved in the expression of genetic damage, e.g. the state of the DNA precursor pool, have been suggested to be important factors in carcinogenesis, the mutagenic specificity of MNU was also studied in the presence of an imbalanced nucleotide pool. Isolation of independent hprt mutant clones from three groups treated in different manners was performed. Two different doses of MNU and a low dose of MNU in combination with hydroxyurea (HU) were employed. Comparison of the results with the two doses of MNU did not indicate any shift in mutation specificity. The majority of the mutations induced by MNU were base substitutions, mostly transitions of GC to AT showing high affinity for the middle base in 5'-purine-G-N-3' sequences (15/18) in the nontranscribing strand, suggesting a difference in repair capacity for the two strands. The relatively high frequency of the base substitutions resulting in splicing defects is explained by the presence of a consensus sequence (5'-purine g-N-3') in the splice sites of the hprt gene. The results from the HU/MNU group showed a few more GC to TA transversions, though not statistically significant, which may be caused by a shift from miscoding to non-coding recognition of the O6 MeG lesion. The same reactive decomposition products formed from MNU are also formed from a variety of other carcinogenic compounds, e.g. N-methyl-N'-nitro-N nitrosoguanidine, dimethylnitrosamine, nitrosocimetidine and 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone, suggesting that our findings concerning the mutagenic specificity of MNU in mammalian cells are valid also for these other compounds as well. PMID- 1934272 TI - Dose-dependent enhancing effects of quinacrine on induction of preneoplastic glutathione S-transferase placental form positive liver cell foci in male F344 rats. AB - Dose-dependent modifying effects of quinacrine on induction of preneoplastic liver cell foci were investigated in male F344 rats. Six week old animals were injected i.p. with N-nitrosodiethylamine (DEN) at a dose of 200 mg/kg, and starting 2 weeks later, rats were given quinacrine at dietary levels of 20, 100 and 500 p.p.m. for 6 weeks. Groups without either DEN or quinacrine treatment were used as controls. At week 3 following DEN administration, all animals were subjected to two-thirds partial hepatectomy, and after killing the animals at week 8, development of preneoplastic liver cell foci was investigated using the glutathione S-transferase placental form (GST-P) as a marker. The numbers and unit areas of GST-P-positive foci per cm2 were significantly increased in the DEN/quinacrine (500 p.p.m.) group as compared to DEN-alone group values. An increase in number was also evident in the 100 p.p.m. but not the 20 p.p.m. treated group, no lesions being induced by quinacrine alone (500 p.p.m.). Electron microscopic study confirmed that quinacrine dose-dependently induces lipidosis in hepatocytes, i.e. markedly myeloid lamellar cytoplasmic inclusion bodies were observed. The results thus demonstrated that quinacrine treatment enhances GST-P-positive liver cell foci development in a dose-dependent way, this effect presumably being related to the induction of lipidosis. PMID- 1934273 TI - Local- and systemic-mediated suppression of contact hypersensitivity in mice by several structurally unrelated classes of tumor promoters. AB - Several structurally unrelated classes of chemicals defined as promoters in the murine skin multistage carcinogenesis protocol were surveyed for their abilities to modify contact hypersensitivity (CHS) responses in SENCAR mice. Sensitization of dorsal skin with 2,4-dinitrofluorobenzene (DNFB) and subsequent challenge of ears 5 days later with DNFB resulted within 24 h in ear swelling. Pretreatment of dorsal skin with multiple applications (2 x/week for 2 weeks) of promoting doses of 12-O-tetradecanoylphorbol-13-acetate (TPA), anthralin, butylated hydroxytoluene hydroperoxide, n-dodecane and ethyl phenylpropionate (EPP) prior to sensitization with DNFB inhibited, to a comparable extent, the subsequent induction of CHS by DNFB challenge. Pretreatment of dorsal skin with promoting doses of benzoyl peroxide resulted in reproducible, but diminished suppression of CHS, relative to that mediated by the other chemical promoters. Application of promoting doses of TPA, anthralin and EPP, but not the other chemicals, to ventral skin prior to DNFB sensitization of dorsal skin also significantly inhibited DNFB-induced CHS. However, suppression of CHS mediated by ventral application of these three chemicals was quantitatively less than that occurring when the chemicals were applied to the site of DNFB sensitization. Collectively, these studies demonstrate that various classes of structurally unrelated tumor promoters have in common the ability to suppress CHS, a cell-mediated immune response. Furthermore, some tumor promoters exert their suppressive effects through both local and systemic processes. PMID- 1934275 TI - Detection of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in cigarette smoke condensate. AB - A carcinogenic heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine (PhIP), was measured in condensate of cigarette mainstream smoke by HPLC. PhIP was detected in all brands of filter-tipped cigarettes analyzed. The mean level of PhIP in the cigarette mainstream smoke was 16.4 ng/cig. PMID- 1934274 TI - Comparative dose-response tumorigenicity studies of dibenzo[alpha,l]pyrene versus 7,12-dimethylbenz[alpha]anthracene, benzo[alpha]pyrene and two dibenzo[alpha,l]pyrene dihydrodiols in mouse skin and rat mammary gland. AB - Comparative studies were conducted of the tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of dibenzo[a,l]pyrene (DB[a,l]P) versus 7,12-dimethyl-benz[a]anthracene (DMBA), the most potent recognized carcinogenic polycyclic aromatic hydrocarbon (PAH); benzo[a]pyrene (B[a]P), the most potent recognized carcinogenic environmental PAH; DB[a,l]P 8,9-dihydrodiol, the K-region dihydrodiol; and DB[a,l]P 11,12-dihydrodiol, precursor to the bay-region diolepoxide. The tumor-initiating activity of DB[a,l]P and B[a]P was compared in the skin of female SENCAR mice at doses of 300, 100 and 33.3 nmol. The mice were promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA) twice-weekly for 13 weeks. DB[a,l]P at all doses induced significantly more tumors than B[a]P at the corresponding dose, with a significantly shorter latency. Subsequently, the tumor initiating activity of DB[a,l]P was compared in the skin of female SENCAR mice to that of DMBA, B[a]P, DB[a,l]P 8,9-dihydrodiol and DB[a,l]P 11,12-dihydrodiol at doses of 100, 20 and 4 nmol. The mice were promoted with TPA twice-weekly for 24 weeks. In addition, groups of mice were initiated with 100 nmol of DB[a,l]P, DMBA, B[a]P, DB[a,l]P 8,9-dihydrodiol or DB[a,l]P 11,12-dihydrodiol and kept without promotion. This experiment showed that in the mouse skin, DB[a,l]P and DB[a,l]P 11,12-dihydrodiol displayed similar tumor-initiating activity with a response inversely proportional to the dose, presumably due to the toxicity of the compounds. At the high dose they elicited tumors earlier than DMBA, though DMBA produced a much higher tumor multiplicity. At the low dose, DMBA, DB[a,l]P and DB[a,l]P 11,12-dihydrodiol exhibited similar tumorigenicities. DB[a,l]P 8,9 dihydrodiol was a marginal tumor initiator. Once again, DB[a,l]P was by far a much stronger tumor initiator than B[a]P. Female Sprague-Dawley rats were treated with 1.0 or 0.25 mumol of DB[a,l]P, DMBA or B[a]P by intramammillary injection at eight teats. DB[a,l]P at both doses was a more potent carcinogen than DMBA at the corresponding dose in the rat mammary gland. B[a]P was a marginal mammary carcinogen, eliciting only a few fibrosarcomas. Thus, these data suggest that DB[a,l]P is the strongest PAH carcinogen ever tested. PMID- 1934276 TI - Inhibitory effect of the non-steroidal anti-inflammatory drug, indomethacin on the naturally occurring carcinogen, 1-hydroxyanthraquinone in male ACI/N rats. AB - The effect of the non-steroidal anti-inflammatory drug indomethacin on 1 hydroxyanthraquinone (1-HA)-induced carcinogenesis was investigated in male ACI/N rats. Animals were fed the diet containing 1.5% 1-HA and simultaneously given indomethacin solution (16 p.p.m.) as drinking water for 48 weeks. The incidences of large bowel neoplasms (adenomas and adenocarcinomas) and forestomach (papillomas) in rats given 1-HA and indomethacin (large intestinal tumors: 0/14, 0%; forestomach tumors: 2/14, 14%) were significantly lower than those in rats given 1-HA alone (large intestinal tumors: 12/27, 44%; forestomach tumors: 14/27, 52%) (P = 0.002 and P = 0.01 respectively). Liver cell adenomas were developed in a rat given 1-HA and no liver tumors in rats treated with 1-HA and indomethacin. Altered liver cell foci were present in rats given 1-HA alone (18/27, 67%) and those given 1-HA and indomethacin (8/14, 57%), but no significant difference in the incidence between the two groups was found. Untreated animals and rats given indomethacin alone had no neoplasms in the large bowel, forestomach and liver. Thus, the non-steroidal anti-inflammatory drug indomethacin significantly inhibited carcinogenesis induced by the naturally occurring carcinogen, 1-HA. PMID- 1934277 TI - DNA adducts in rat lung, liver and peripheral blood lymphocytes produced by i.p. administration of benzo[a]pyrene metabolites and derivatives. AB - DNA adducts produced in vivo in rat lung, liver and peripheral blood lymphocytes following the i.p. administration of several synthetic benzo[a]pyrene (B[a]P) metabolites and ring-substituted derivatives have been analyzed by the nuclease P1 version of the 32P-postlabeling assay. These include 1-, 2-, 3-, 4-, 5-, 6-, 7 , 8-, 9-, 10-, 11- and 12-hydroxy-B[a]P, (+/-)-B[a]P-trans-4,5-dihydrodiol, (+/-) B[a]P-trans-7,8-dihydrodiol, (+/-)-B[a]P-trans-9,10-dihydrodiol and B[a]P-7,8 dione. Among the monohydroxy derivatives, only 2-, 9- and 12-hydroxy-B[a]P produced detectable adducts. The only disubstituted derivative studied that produced adducts was the trans-7,8-dihydrodiol. The resulting DNA adducts were compared to those produced in each tissue by administration of B[a]P. 9-Hydroxy B[a]P and B[a]P-trans-7,8-dihydrodiol each lead to the formation of major B[a]P adducts seen in lung and liver respectively. None of the adducts derived from either 2-hydroxy-B[a]P or 12-hydroxy-B[a]P were observed following administration of B[a]P alone. PMID- 1934278 TI - Contribution of patient history to the glutathione S-transferase activity of human lung, breast and colon tissue. AB - Overexpression of the glutathione S-transferases (GSTs) and their involvement in the detoxification of anticancer agents has prompted numerous investigations of the enzyme activity of human tumor tissue. This study represents an in-depth evaluation of the contribution of patient history and pathological status to the GST activity of various human tissues. GST activity was elevated significantly in tumors of the lung, breast and colon as compared to unmatched and matched normal tissue from the same organ. The GST activity of primary breast tumors varied significantly with the stage of the tumor. Breast tumors previously treated with both radiation and chemotherapy had significantly lower levels of GST activity than untreated tumors. Neither progesterone nor estrogen receptor content was associated with the GST activity in primary breast tumors. Colon metastases possessed higher levels of GST activity than primary colon tumors but enzyme activity was independent of the Duke's classification of the tumor. Only tumors of the left colon had levels of GST activity that were higher than those of adjacent normal mucosa. No relationship was evident between either age or sex and the GST activity of any of the tissues examined. GST activity levels may reflect the site-specific ability of tissues to provide cellular protection against xenobiotics. PMID- 1934279 TI - Metabolism of benzo[a]pyrene by human melanocytes in culture. AB - Benzo[a]pyrene (B[a]P) is a ubiquitous environmental pollutant and known skin carcinogen. In the present study, in vitro addition of [3H]B[a]P to normal human melanocytes in culture, isolated from adult human skin, resulted in the metabolism of [3H]B[a]P both intracellularly and extracellularly. HPLC analysis showed that [3H]B[a]P-9,10- and 7,8-diol were the major intracellular and extracellular metabolites followed by 3,6-quinone, 9-hydroxy and 3-hydroxy metabolites. Significant amounts of the [3H]B[a]P metabolites were found to be present in the sonicated cell suspension and culture medium as the glucuronide and sulfate conjugates. In total 37.3% of the [3H]B[a]P added in the culture medium was metabolized by melanocytes, of which 21.1% was quantified as the intracellular and 16.2% as the extracellular metabolites. Our data show that human melanocytes are capable of metabolizing B[a]P. PMID- 1934280 TI - Selective in vivo inhibition of rat mammary 7,12-dimethylbenz[a]anthracene-DNA adduct formation by dietary butylated hydroxytoluene. AB - The in vivo formation of specific 7,12-dimethylbenz[a]-anthracene (DMBA)-DNA adducts in the mammary gland of the female Sprague-Dawley rat was studied in response to dietary butylated hydroxytoluene (BHT). Dietary BHT concentrations of 0.4 and 0.8% significantly inhibited total DMBA-DNA binding by 41.5 and 35.6% respectively, as compared to controls. However, the decrease in total binding associated with intake of BHT was not due to a uniform inhibition in the formation of all individual adducts. The formation of two adducts resulting from the binding of the anti-dihydrodiolepoxide of DMBA to deoxyguanosine (anti-dGuo) was significantly decreased by a combined average of 51.5% for rats fed BHT supplemented diets as compared to controls. However, syn-derived DMBA-DNA adducts were not consistently inhibited by dietary BHT. Adduct formation resulting from the binding of the syn-dihydrodiolepoxide of DMBA to deoxyadenosine (syn-dAdo) was significantly inhibited only for rats fed a diet supplemented with 0.4% BHT. The formation of the syn-dGuo adduct was not affected by the feeding of BHT supplemented diets. These results suggest that in vivo inhibition by BHT of mammary DNA adducts formed from the anti-diastereomer of DMBA may be an important contribution to the inhibitory effect of BHT on the initiation stage of DMBA induced mammary carcinogenesis. PMID- 1934282 TI - Gene specific DNA repair. PMID- 1934281 TI - Release of N2,3-ethanoguanine from haloethylnitrosourea-treated DNA by Escherichia coli 3-methyladenine DNA glycosylase II. AB - 3-Methyladenine DNA glycosylase II (Gly II), purified from Escherichia coli cells which carry the plasmid PYN1000, has been tested for its ability to release N2,3 ethanoguanine from DNA modified by the antitumor agent N-[2-chloroethyl-1,2-14C] N'-cyclohexyl-N-nitrosourea ([14C]CCNU). Gly II has been shown to release N2,3 ethanoguanine in a protein- and time-dependent manner at a rate that exceeds the rate at which this enzyme releases other alkylated bases from [14C]CCNU-modified DNA. This finding widens the known substrate specificity for Gly II to include a modified base which bears an exocyclic ring structure, a class of modifications caused by a variety of chemical carcinogens. PMID- 1934283 TI - Cell-to-cell communication: a differential response to TGF-beta in normal and transformed (BEAS-2B) human bronchial epithelial cells. AB - The effects of transforming growth factor beta (TGF-beta) on cell-to-cell communication were investigated in the log phase of growth in normal BE and in adenovirus-12 SV40 hybrid virus transformed BE cells (strain BEAS-2B). Gap junctions in these cells were identified immunocytochemically. Exposure of BE cells to exogenous TGF-beta (0.04-4.0 pM) in serum-free keratinocyte growth medium (KGM) for 1 or 24 h reduced the rate of fluorescent dye transfer (i.e. cell-to-cell communication) by 30-50% in BE cells. Inversely, in BEAS-2B cells, TGF-beta after 1 h induced a 2- to 10-fold increase in the rate of dye transfer. After 24 h of TGF-beta, communication among BEAS-2B cells was not significantly different from controls (no exogenous TGF-beta). The protein kinase C (PKC) inhibitor H-7 induced a dose-dependent enhancement in communication, which was even higher in the presence of TGF-beta (4 pM X 24 h). The calmodulin antagonist W-7 enhanced communication in BEAS-2B cells independently of the presence of TGF beta. In keratinocyte basal medium (KBM) supplemented with EGF (5 ng/ml) or with TGF-beta (4.0 pM) dye transfer was reduced or enhanced respectively. The combination of EGF and TGF-beta in KBM antagonized the stimulatory effect of the latter on communication in BEAS-2B cells. In BE cells, continuous exposure (4 days) to TGF-beta in KGM induced a dose-dependent inhibition of proliferation and an increased expression of a keratinized, epidermoid phenotype. This correlated with a reduction in the expression of a mucous secretory phenotype. Increased exposure to TGF-beta (0.04-4.0 pM) decreased the labeling index in BEAS-2B cells, but the cells retained a growth advantage over normal BE cells, and did not express a keratinized epidermoid morphology. With respect to dye transfer as an index of cell-to-cell communication, we conclude (i) that an inhibition or enhancement of communication is involved in the response of bronchial epithelial cells to mitogens (e.g. epidermal growth factor) or growth inhibitors (e.g. TGF beta), (ii) that PKC and Ca(2+)-calmodulin-dependent processes regulate dye transfer, and (iii) the effects of TGF-beta are mediated by PKC. PMID- 1934285 TI - Effects of gastrointestinal peptides on azoxymethane-treated colonic mucosa in vitro. AB - An organ-culture system has been used to investigate the effect of certain gastrointestinal peptides on the morphology and cell proliferation of explants of azoxymethane (AOM)-treated colonic mucosa. Our aim was to ascertain whether such factors play a direct part in the maintenance of hyperplastic changes in the large intestine. Explants of AOM-treated colonic mucosa from 15 animals were maintained in a serum-free medium in the presence of either gastrin-17 (250 pg/ml and 250 ng/ml), peptide YY (80 pmol/l and 160 pmol/l) epidermal growth factor (EGF) (10 ng/ml and 100 ng/ml) or the C-terminal fragment of glucagon-37 (30 pmol/l) for a period of up to 7 days. Other explants (controls) received fresh medium only each day. After 1, 2, 3, 5 and 7 days of culture both experimental and control explants received vincristine (4 micrograms/ml) for 3 h prior to fixation. The proportion of vincristine-arrested metaphases within the explants was determined together with crypt length. Neither gastrin nor peptide YY was found to influence cell division at either concentration. Despite an initial inhibitory effect, both concentrations of EGF exerted a trophic effect which increased with time. The glucagon-37 fragment caused an immediate increase in proliferation which then declined as time progressed. None of these factors, however, were able to maintain the hyperplastic changes seen in the pre-culture samples of AOM-treated mucosae. PMID- 1934284 TI - Effects of biochanin A on metabolism, DNA binding and mutagenicity of benzo[a]pyrene in mammalian cell cultures. AB - The search for potential chemopreventive agents from higher plants based upon alteration of benzo[a]pyrene (B[a]P) metabolism in cell cultures resulted in isolation of the isoflavone biochanin A. The mechanisms by which biochanin A inhibits the metabolic activation of B[a]P were investigated in hamster embryo cell cultures. Biochanin A treatment inhibited the metabolism of B[a]P to water soluble metabolites. B[a]P-9,10-diol and B[a]P-7,8-diol by 44, 60 and 52% respectively. Biochanin A inhibited the formation of glucuronide conjugates from 3-OH-B[a]P and 9-OH-B[a]P. Biochanin A also inhibited, in a dose-dependent manner, oxidation of B[a]P by homogenate (S-9) of Aroclor 1254-induced rat liver. Exposure of hamster embryo cells to biochanin A and [3H]B[a]P resulted in a decrease in the total level of [3H]B[a]P bound to DNA compared with the control groups at all time points studied between 24 and 120 h. This decrease was due to reduction in the formation of DNA adducts from both (+)-anti-B[a]P-diolepoxide and (+)-syn-B[a]P-diolepoxide. In a hamster embryo cell-mediated V79 cell mutation assay, biochanin A treatment resulted in a dose-dependent reduction in the number of B[a]P-induced mutants. These results indicate that biochanin A inhibits metabolic activation of B[a]P to mutagenic intermediates and warrants further investigation as a potential chemopreventive agent. PMID- 1934287 TI - Effect of proliferative state on glutathione S-transferase isoenzyme expression in cultured rat liver epithelial cells. AB - A specific biochemical phenotype is expressed during chemical hepatocarcinogenesis, which includes increased activity of the various isoenzyme forms of glutathione S-transferase (GST) composed of class alpha (Ya/Yc), class mu (Yb) and class pi (Yp) gene products. In vitro cell lines of normal and chemically transformed rat liver epithelial cells provide an opportunity to examine the regulation of expression of GST isoenzymes. We have studied the effect of the state of proliferation in culture on both the enzymic activity and the isoenzyme-specific mRNA expression. In normal rat liver epithelial cells (WB F344), basal expression of the Yp subunit decreases, and of the Yb subunit increases, in cells at confluence compared with those in logarithmic-phase growth. In a subline of WB-F344 cells that has been chemically treated in vitro (GN6), there was greater Yp expression; however, the effect of growth status on both subunits was the same as in the nontransformed WB-344 cells, and the Ya subunit was not expressed. Inhibition of RNA synthesis with actinomycin D was limited, demonstrating pronged half-lives of the GST mRNAs, and shows a slightly greater decrease in GST-Yp specific mRNA levels in the confluent cells. Also nuclear run-off experiments demonstrate identical transcription rate in confluent and pre-confluent cells. These data suggest that the increase in Yp steady-state RNA in preconfluent cells is due to increased stability of the GST-Yp mRNA. In tumor cells derived from GN6 cells, the regulatory effects of growth status on the Yb and Yp expressions were absent. However, in these cells Ya subunit was expressed and this was subject to the effects of cell proliferation. We conclude that the growth status of cells in culture exerts a significant regulatory control on the GST isoenzyme gene expression. The effects are probably mediated at independent regulatory sites in each gene. The state of transformation of rat liver epithelial cells may determine responsiveness to this effect. PMID- 1934286 TI - Preneoplastic changes of xenotransplanted human distal airway epithelium induced by systemic administration of 4-nitroquinoline-1-oxide to host nude mice. AB - To elucidate a possible role of hematogenously transported carcinogens in pathogenesis of peripheral lung carcinoma in humans, we investigated whether the bronchiolar and alveolar epithelial cells of adult human lung xenografts in nude mice could be a target for the chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) after its systemic administration to the host mice. Peripheral lung tissues from adult humans were transplanted s.c. into nude mice, and 4NQO (15 mg/kg) was administered s.c. to the host mice at a site distant from the xenografts at 2 and 3 weeks after transplantation. The human lung xenografts were maintained for from 20 to 52 weeks, and then serial sections were examined histologically and immunohistochemically. Three types of epithelial changes, i.e. epidermoid metaplasia, papillary hyperplasia of columnar and epidermoid cells, and atypical adenomatous hyperplasia, were induced in the 4NQO group, with a statistically significant difference for these combined epithelial lesions (P less than 0.01) and for epidermoid metaplasia (P less than 0.05) compared to the control group. Some epidermoid metaplasias showed significant nuclear atypia. In addition, almost all foci of epidermoid metaplasia and papillary hyperplasia contained cells positive for carcinoembryonic antigen, suggesting both types of the lesions were preneoplastic. The morphologic characteristics of the atypical adenomatous hyperplasia were very closely similar to those of the hitherto reported preneoplastic or putative neoplastic lesions in the human peripheral lung. Our results indicated that the alveolar and bronchiolar epithelial cells of human lung xenografts were affected by systemically applied 4NQO, and subsequently underwent transformation to a preneoplastic state. PMID- 1934288 TI - Sex-differentiated deoxycholic acid promotion of rat liver carcinogenesis is under pituitary control. AB - The influence of continuous growth hormone (GH) infusion and of implantation of ectopic pituitary grafts (PG) to male rats on the sex differences (male greater than female) in efficiency of promotion with dietary deoxycholic acid (DCA; 0.5% w/w) was studied in the livers of diethylnitrosamine (DEN)-initiated Wistar rats. For comparison, liver regeneration after partial hepatectomy (PH) was examined in differently treated animals. The endpoints examined included the number and size of enzyme-altered foci, hepatic c-myc expression and liver weight gain. The area per focus was 2- to 3-fold larger in initiated, DCA-treated males than in the corresponding PG-bearing males, GH-treated males and in females. The expression of the c-myc gene was increased approximately 2-fold in initiated and promoted males, while the increase in females was very small. In both groups of hormone treated males the expression was at the same level as in females, significantly lower than in the corresponding DEN/DCA-treated males. Liver weight gain in response to PH in initiated as well as uninitiated rats of both sexes was significantly stimulated by DCA. No sex differences or effects of PG on regeneration could be discerned. In conclusion, a sex difference, regulated by a pituitary influence, in focal growth and in c-myc expression was observed during DCA promotion of DEN-initiated rats. This might indicate a correlation between the GH-regulated, proliferation-associated c-myc gene and focal growth during sex differentiated promotion in rat liver. Furthermore, the lack of sex differences in liver weight gain in response to PH during DCA treatment suggests that selective mitoinhibition is not involved, and might in this model indicate hormone-dependent selective stimulation of focal growth as a mechanism for tumor promotion. PMID- 1934289 TI - Phytic acid and minerals: effect on early markers of risk for mammary and colon carcinogenesis. AB - This study determined the effect of inositol hexaphosphate or phytic acid (PA; 1.2%), Ca (1.5%) and Fe (535 p.p.m.) alone, and PA in combination with Ca or Fe in a high-fat diet (25%) on the labeling (LI) and mitotic (MI) cell proliferation indices, nuclear aberration (NA) and intraductal proliferation (IDP) in the mammary gland, as well as the LI in colonic epithelial cells. Diet supplementation with PA alone caused reductions (P less than 0.05) in the colon LI by 18%, and in the LI and NA in the total mammary gland structures of mice by 29 and 30% respectively. Supplementation with Fe or particularly Ca caused increases in the colon LI and in the mammary LI, MI, NA and IDP but these were reduced by 25-53% (P less than 0.05) in the presence of PA. These results support the hypothesis that PA may reduce the risk for both colon and mammary cancer and its effect is related to its mineral binding ability. Furthermore, significant relationships (P less than 0.01) were observed between the LI and MI or NA in the total structures of the mammary gland. The number of IDPs also related (P less than 0.05) to LI or NA in the terminal end bud structure of the mammary gland, suggesting that highly proliferating mammary cells, particularly in the terminal end bud structure, are of greater risk for nuclear damage and development to IDP. A significant relationship (P less than 0.01) was observed between the cell proliferation in the mammary gland and that in the colon, indicating that both tissues can be influenced similarly by dietary constituents. PMID- 1934290 TI - Differential oxidative stress induced by two different types of skin tumor promoters, benzoyl peroxide and 12-O-tetradecanoylphorbol-13-acetate. AB - The oxidative stress induced in vivo by benzoyl peroxide (BzPo) or 12-O tetradecanoylphorbol-13-acetate (TPA) was evaluated in terms of chemiluminescence (CL) emitted by SENCAR mouse skin, a non-invasive method that allows an estimation of overall oxidative stress. The ability of a biomimetic superoxide dismutase, copper(II)(3,5-diisopropylsalicylate)2 (CuDIPS), to inhibit that response was also evaluated. A single application of BzPo to mouse skin resulted in a dose-dependent increase in CL up to 0.083 mumol. Sequential treatment with BzPo in a dose used for tumor promotion resulted in a fall in CL induced by the second topical application. There were no differences between initiated and non initiated mice in their responses to BzPo-induced CL. CuDIPS, an inhibitor of tumor promotion, was an effective inhibitor of CL in all the protocols evaluated. Conversely, ZnDIPS and DIPS did not inhibit CL. Phenolic antioxidants induced partial inhibition of CL. Unlike BzPo treatment, a single application of TPA up to 105 nmol did not induce an increase in CL, but the second topical application with TPA in a dose used for tumor promotion resulted in a small but significant increase in CL. However, these values of CL were much smaller than the CL induced by BzPo. Our results show a differential response of the skin in terms of the oxidative stress induced by BzPo or TPA. PMID- 1934291 TI - In vivo and in vitro persistence of pyridyloxobutyl DNA adducts from 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone. AB - The persistence of pyridyloxobutyl DNA adducts in lung and liver of F-344 rats treated with the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl) 1-butanone (NNK) was investigated. The levels of these adducts were determined at various time points up to 4 weeks post s.c. injection of [5-3H]NNK (0.8 mg/kg body wt). Maximal levels of the adducts were observed between 4 and 24 h in both tissues. The disappearance of the adducts from lung and liver DNA was multiphasic with initial half-lives of 50 and 38 h respectively. In both cases, detectable levels of the pyridyloxobutyl adducts were observed at 4 weeks post injection. The in vitro rate of adduct disappearance was studied using calf thymus DNA reacted with 4-(acetoxymethylnitrosamino)-1-(3-[5-3H]pyridyl)-1-butanone in the presence of esterase. Adduct levels were measured for up to 2 weeks after the initiation of the experiment. The decomposition of these adducts was triphasic with half-lives of 6, 120 and 430 h. The multiphasic disappearance of the pyridyloxobutyl adducts suggests that there is more than a single adduct generated upon pyridyloxobutylation of DNA and that at least one of these adducts has a significant lifetime in DNA. PMID- 1934292 TI - Suppression of benzo[a]pyrene metabolism by accumulation of triacylglycerols in rat hepatocytes: effect of high-fat and food-restricted diets. AB - Diet has been implicated as a major determinant of chemical carcinogenesis. Accordingly, rates of benzo[a]pyrene (B[a]P) metabolism were compared in hepatocytes isolated from rats maintained on control, high-fat or food-restricted AIN-76A diets. Rats maintained on the food-restricted diet were given 65% of food consumed by the control group fed ad libitum. The high-fat diet group had free access to a modified AIN-76A diet in which the amount of corn oil was increased 4 fold at the expense of digestible carbohydrates. The triacylglycerol content in hepatocytes varied in direct proportion to dietary fat and calories and was 66 +/ 5, 105 +/- 7 and 192 +/- 16 nmol/mg dry wt in cells isolated from rats fed food restricted, control and high-fat diets respectively. In contrast, the rate of B[a]P metabolism was highest in hepatocytes from rats maintained on the food restricted diet and lowest in cells from animals given the high-fat diet (i.e. food-restricted greater than control greater than high-fat). Thus, an inverse correlation existed between the rate of B[a]P metabolism and the content of triacylglycerols in hepatocytes. At a cell density of approximately 2 mg dry wt/ml, rates of B[a]P (40 microM) metabolism were 1324 +/- 186, 1150 +/- 198 and 829 +/- 76 pmol/mg dry wt/h, respectively, in hepatocytes isolated from rats fed food-restricted, control and high-fat diets. When cells were incubated with a lower concentration of B[a]P (10 microM), the rate of B[a]P metabolism was greater than 2-fold higher in hepatocytes from rats fed the food-restricted diet compared to the rate measured in cells from the high-fat group. Glucuronidation of B[a]P metabolites in hepatocytes from rats fed high-fat diet was also approximately 30% lower than rates determined for control and food-restricted groups. These diet-induced alterations in rates of B[a]P metabolism occurred in the absence of changes in specific activity of arylhydrocarbon hydroxylase or UDP glucuronosyltransferase in liver microsomes. Further, the rate of 7 ethoxycoumarin metabolism, a more hydrophilic substrate, was not affected by diet and B[a]P but not 7-ethoxycoumarin accumulated in hepatic lipid droplets. Thus, diet-induced changes in intracellular triacylglycerol, particularly in lipid droplets, may alter access of B[a]P to binding sites on arylhydrocarbon hydroxylase and thereby modulate B[a]P metabolism in intact hepatocytes. PMID- 1934293 TI - Effects of monoterpenoids on in vivo DMBA-DNA adduct formation and on phase I hepatic metabolizing enzymes. AB - We have previously demonstrated the anticarcinogenic effects of monocyclic monoterpenes such as limonene when given during the initiation phase of 7,12 dimethylbenz[a]anthracene (DMBA)-induced mammary cancer in Wistar-Furth (WF) rats. Here we investigated the possible mechanisms for this chemoprevention activity including limonene's effects on DMBA-DNA adduct formation and hepatic metabolism of DMBA. Twenty-four hours after carcinogen administration, there were approximately 50% of the total DMBA-DNA adducts found in control animals formed in the liver, spleen, kidney and lung of limonene-fed animals. While circulating levels of DMBA and/or its metabolites were not different in control and limonene fed rats, there was a 2.3-fold increase in DMBA and/or DMBA-derived metabolites in the urine of the limonene-fed animals. Studies of the effects of limonene and sobrerol, a hydroxylated monocyclic monoterpenoid with increased chemoprevention activity, on phase I metabolizing enzymes revealed that these terpenoids modulated cytochrome P450 (CYP) and epoxide hydratase (EH) activity. The 5% limonene diet increased total CYP to the same extent as phenobarbital (PB) treatment when compared to control, while 1% sobrerol (isoeffective in chemoprevention to 5% limonene) did not. However, both 5% limonene and 1% sobrerol diets greatly increased the levels of microsomal EH protein and associated hydrating activities towards benzo[a]pyrene 4,5-oxide when compared to control and PB treatment. These changes also modified the rate and regioselectivity of in vitro microsomal DMBA metabolism when compared to PB treatment or control. Identification of the specific isoforms of CYP induced by these terpenoids was performed using antibodies to CYP isozymes in Western blot analysis and inhibition studies of microsomal DMBA metabolism. Five per cent limonene was more effective than 1% sobrerol at increasing the levels of members of the CYP2B and 2C families but was equally effective at increasing EH. Furthermore, both terpenoid diets caused increased formation of the proximate carcinogen, DMBA 3,4-dihydrodiol. While these terpene-induced changes in hepatic CYP and EH do not explain the anticarcinogenic mechanism of these chemopreventive agents, or the ability of limonene systemically to reduce DMBA-DNA binding, they do reveal novel and selective induction mechanisms of hepatic enzymes. PMID- 1934294 TI - Dose response and proliferative characteristics of aberrant crypt foci: putative preneoplastic lesions in rat colon. AB - Foci of aberrant crypts (ACF) have been identified in the unsectioned methylene blue stained rodent colons and hypothesized to represent precursor lesions of colon cancer. In the present study, induction and growth characteristics of ACF were investigated in response to a single injection of varying dosages of 1,2 dimethylhydrazine-2HCl (DMH), a colon carcinogen. Female Sprague-Dawley rats were given a single injection of DMH (5-150 mg/kg). Two and 19 weeks after the injection, animals were killed and their distal 10 cm of colons were enumerated for the number and crypt multiplicity of ACF. Number of ACF increased with increasing dosages of DMH plateauing at 100 mg/kg. However, percentage of ACF exhibiting different crypt multiplicity (1 to greater than 4) were similar among different dose groups. Aberrant crypts and normal crypts were enumerated for total number of cells and number and distribution of S-phase cells along the crypt height 19 weeks after DMH injection after autoradiography. The labeling index (LI) (percentage of S-phase cells) and LI along the crypt height were determined. Compared to the surrounding normal crypts, aberrant crypts exhibited significantly higher (P less than 0.05) number of cells (1122 +/- 81 versus 411 +/- 28) and higher (P less than 0.05) LI (21 +/- 1 versus 12 +/- 1). For the eight ACF analysed in the present study, the distribution of S-phase cells in the aberrant crypts were similar to that of normal crypts in that S-phase cells were restricted to the lower two-thirds of the crypts rather than distributed throughout the height of the crypts as reported for adenomatous epithelium. PMID- 1934295 TI - Spectroscopic characteristics and site I/site II classification of cis and trans benzo[a]pyrene diolepoxide enantiomer-guanosine adducts in oligonucleotides and polynucleotides. AB - The highly tumorigenic isomer (+)-7,8-dihydroxy-anti-9, 10-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] and its non-tumorigenic enantiomer (-) anti-BPDE are known to react predominantly with the exocyclic amino group (N2) of deoxyguanine in DNA and to form adducts of different conformations. The spectroscopic characteristics (UV absorbance, fluorescence and circular dichroism) of stereochemically defined (+)-trans, (-)-trans, (+)-cis and (-)-cis d(5'-CACATGBPDETACAC) adducts in the single-stranded form, or complexed with the complementary strand d(5'-GTGTACATGTG) in aqueous solution, were investigated. The spectroscopic characteristics of the double-stranded d(5' CACATGBPDETACAC).d(5'-GTGTACATGTG) adducts can be interpreted in terms of two types of conformations. In site I-type conformations, there is an approximately 10 nm red shift in the absorption maxima, which is attributed to significant pyrenyl residue-base interactions; in site II-type adducts, the red shift is only approximately 2-3 nm, and the pyrene ring system is located at external, solvent exposed binding sites. The spectroscopic characteristics of the BPDE-modified duplexes are of the site II type for the (+)- and (-)-trans, and of the site I type for the (+)- and (-)-cis adducts. In adducts derived from the binding of (+) anti-BPDE to poly(dG-dC).(dG-dC) and poly(dG).(dC), the trans/cis BPDE-N2-dG adduct ratio is 6 +/- 1; in the case of (-)-anti-BPDE this ratio is only 0.4 +/- 0.1 and 0.6 +/- 0.15 in poly(dG-dC).(dG-dC) and poly(dG).(dC) respectively. The spectroscopic properties of these BPDE-modified polynucleotide adducts are consistent with those of the BPDE-modified oligonucleotide complexes; the cis adducts are correlated with site I adduct conformations, while the trans adducts are of the site II type. The correlations between adduct characteristics and biological activities of the two BPDE enantiomers are discussed. PMID- 1934296 TI - Carotenoids enhance gap junctional communication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to their cancer chemopreventive action. AB - We have previously demonstrated that diverse carotenoids inhibit chemically induced neoplastic transformation in 10T1/2 cells. To address their mechanism of action, the effects of six diverse carotenoids, with or without provitamin A activity, on gap junctional communication and lipid peroxidation have been investigated. beta-Carotene, canthaxanthin, lutein, lycopene and alpha-carotene increased gap junctional intercellular communication in a dose-dependent manner in the above order of potency, whereas m-bixin was inactive at concentrations up to 10(-5) M. alpha-Tocopherol, a potent chain-breaking antioxidant, caused a marginal enhancement of junctional communication. The enhancement of junctional communication by diverse carotenoids showed a strong statistical correlation with their previously determined ability to inhibit methylcholanthrene-induced neoplastic transformation (r = -0.75). All carotenoids tested inhibited lipid peroxidation, but with differing potencies. alpha-Tocopherol was the most active inhibitor followed by m-bixin. The capacity of carotenoids or alpha-tocopherol to inhibit lipid peroxidation was neither consistent with their ability to inhibit neoplastic transformation (r = 0.30) nor to increase junctional communication (r = 0.12). Since junctional communication appears to play an important role in cell growth control and carcinogenesis, we propose that in this system carotenoid enhanced intercellular communication provides a mechanistic basis for the cancer chemopreventive action of carotenoids. These data also imply that carotenoids function in a manner analogous to retinoids in the 10T1/2 assay system. Interestingly this activity appears independent of their provitamin A status. PMID- 1934298 TI - Inhibitory effects of soybean trypsin inhibitor on induction of pancreatic neoplastic lesions in hamsters by N-nitrosobis(2-oxopropyl)amine. AB - The effects of simultaneous soybean trypsin inhibitor (SBTI) treatment on initiation of pancreatic carcinogenesis by N-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Female Syrian golden hamsters were given five weekly s.c. injections of BOP at a dose of 10 mg/kg while being administered a diet containing 5% SBTI for 5 weeks (BOP + SBTI group). Two other groups of 30 animals each received the s.c. injections of BOP or the 5% SBTI diet for the same period, alone (BOP and SBTI groups respectively). Total numbers of pancreatic dysplastic lesions in hamsters of the BOP+SBTI group were significantly decreased as compared to the BOP group values, though the incidences of pancreatic adenocarcinomas were not significantly different. Atrophic changes were, however, more severe in the BOP group than in the BOP+SBTI group pancreatic exocrine tissue, showing that treatment with SBTI was effective for protection of acinar cells from carcinogen toxicity. PMID- 1934297 TI - Increase of CYP1A1 mRNA and AHH activity by inhibitors of either protein or RNA synthesis in mouse hepatocytes in primary culture. AB - Regulation of CYP1A1 gene expression in mouse hepatocytes from C57/BL6 strain in primary culture was investigated with respect to aryl hydrocarbon hydroxylase (AHH) activity and mRNA levels. Small amounts of the CYP1A1 gene transcripts were detected without the presence of any known AHH inducers but after medium change. Maximal level of expression was approximately 6-9 h after the procedure, followed by a decrease to an undetectable level 24 h later. After temporary treatment of hepatocytes for 10 h with cycloheximide, an inhibitor of protein synthesis, AHH activity measured 14 h later was at a normal low level, although medium-change associated CYP1A1 mRNA were increased by cycloheximide treatment. However, if cells were treated with either actinomycin D, alpha-amanitin or cordycepin, which are inhibitors of RNA synthesis, after exposure to cycloheximide, prominent induction of AHH activity was observed, the levels being almost equal to those for hepatocytes treated with benz[a]anthracene, a potent AHH inducer. With the same experimental protocol benz[a]anthracene-induced AHH activity was enhanced approximately 4-fold. After washing out cycloheximide and/or benz[a]anthracene, the decrease in the mRNA amounts was delayed in the presence of actinomycin D and half amounts were found even 12 h later; while without actinomycin D they reduced with a half-life of 3-4 h. The observations indicate that CYP1A1 gene expression might be regulated at the post-transcriptional level with compensatory mRNA stabilization under conditions of blocked further production, resulting in elevation of AHH activity. PMID- 1934299 TI - Recovery of hyperplastic responsiveness in rat liver after dosing with the peroxisome proliferator methylclofenapate. AB - Methylclofenapate (MCP) was administered daily by gavage (25 mg/kg) for 7 days to groups of adult male rats. Dosing was interrupted for 28, 35, 56, 70 or 84 days and then resumed (25 mg/kg by gavage at 0 and 24 h). During the second period of dosing animals were killed in groups of three at 6, 12, 18, 24, 30, 36, 42 and 48 h after the resumption of dosing. Hepatocytes in S-phase, labelled with bromodeoxy-uridine, were analysed by flow cytometry, cell sorting and microscopy. It was observed that total S-phase activity was just significantly elevated (approximately 20% of maximum) over corn oil controls after an interval of 28 days between initial and subsequent dosing periods. After an interval of 35 days total S-phase activity was approximately 65% of maximum, and full hyperplastic responsiveness, equal to that observed in naive animals given MCP, was detected after interruptions in dosing of 56, 70 and 84 days. The recovery of S-phase responsiveness during the interruptions in dosing was accompanied by an increase in the proportion of 2 X 2N hepatocytes from approximately 10% in animals dosed continuously with MCP, to approximately 11.4% after 28 days interruption, 17% after 35 days and control levels (approximately 20%) after 56, 70 and 84 days. Irrespective of the magnitude of the hyperplasia elicited by the second period of dosing with MCP, the proportion of 2 X 2N cells was reduced to the same levels as those observed in animals dosed continuously with MCP (approximately 10%). Very low S-phase activity (0.05%) was observed in animals dosed continuously with MCP, this level of activity being similar to that in animals given corn oil continuously. PMID- 1934300 TI - Comparison of DNA alkali-labile sites induced by 4-(methylnitrosamino)-1(3 pyridyl)-1-butanone and 4-oxo-4-(3-pyridyl)butanal in rat hepatocytes. AB - 4-Oxo-4-(3-pyridyl)butanal (OPB) is an aldehyde formed during the activation of the tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Using the DNA alkaline elution technique, the properties of DNA alkali labile sites induced in the isolated rat hepatocytes by NNK and OPB were compared. The DNA single-strand break (SSB) frequencies in vitro, as measured by the elution rate (ER), ranged from 0.015 to 0.479 and were proportional (r2 = 0.991) to the dose (0-2 mM) of OPB. These concentrations, however, were slightly cytotoxic. For example, the LC50 after 4 h of exposure was 2.8 mM. This suggests that OPB-induced DNA SSB result from additive effects of OPB-DNA interaction and the indirect DNA damage associated with OPB cytotoxicity. NNK induced a significant and dose-dependent increase of DNA fragmentation at concentrations ranging from 0.5 to 5.0 mM with ER values ranging from 0.012 to 0.274 (r2 = 0.951). Genotoxicity as measured by the DNA-damaging potency coefficient (DDP) was 810, 345, 131 and 75 for N-methyl-N-nitrosourea (MNU), N-nitrosodimethylamine (NDMA), OPB and NNK respectively. Both MNU- and NNK-induced DNA lesions showed increased lability with increased pH (from 12.1 to 12.5) of the eluting buffer (r2 = 0.979 and 0.967 respectively). In contrast, the number of OPB-induced labile sites were not affected by increases in the pH. These results indicate that OPB is not the metabolite contributing the majority of alkali-labile sites generated by NNK. The filter elution procedure was used to study the in vitro rejoining of SSB in DNA induced by NNK. The extent of DNA SSB rejoining after 18 h of culture of hepatocytes in NNK-free medium were dependent on the concentration of NNK (0.5, 2.0 and 5.0 mM) and ranged from 50 to 90%. Rats were injected s.c. with NNK (0.39 mmol/kg). SSB frequency in liver DNA increased rapidly and reached a maximum 12 h after injection. DNA SSB frequency declined during the next 2 weeks with biphasic kinetics. The fast phase (75% rejoining of DNA SSB between 12 h and 2 days) was followed by a slow one (25% of DNA SSB maintained during the next 5 days but not present after 2 weeks). The results of this study better define the role of OPB-induced DNA damage. The persistence of DNA SSB in the liver of NNK-treated rats reflects the inability of this tissue to repair all DNA lesions. PMID- 1934301 TI - Sister chromatid exchange frequency in Hodgkin's disease patients with elevated in vivo hprt mutant frequencies. AB - The frequency of sister chromatid exchanges (SCEs) was determined in Hodgkin's disease (HD) patients prior to therapy, following radiotherapy, and following combined radiotherapy and chemotherapy. The frequency of hprt- mutants in these patients has been reported previously. The frequency of SCEs and hprt- mutants in the same individuals were compared. In non-HD controls the mean SCE frequency and the mean of high SCE frequency cells (HFCs) were significantly increased by smoking, while mutant frequency (MF) showed no effect. Untreated HD patients had mean SCEs, mean HFCs and mean MFs that were higher than non-MD controls. In treated patients, mean SCE and HFC frequencies were lower than untreated patients and non-HD controls, while their MFs were significantly elevated. Overall, SCE frequency was not correlated with MF in control or HD patient groups, suggesting that these biomarkers may reflect, in this case, fundamental biological differences between these processes. PMID- 1934302 TI - Inhibition of N-nitrosomethylbenzylamine-induced esophageal neoplasms by the Bowman-Birk protease inhibitor. AB - Model systems in which carcinogenesis by given agents can be prevented or reduced offer a means of gaining insight into the mechanism(s) of action of carcinogens and the feasibility of chemoprevention in humans. In the current study, the ability of the soy-bean derived Bowman-Birk protease (BBI) to suppress esophageal carcinogenesis induced by N-nitrosomethylbenylamine (NMBzA) was examined. Esophageal lesions were produced in male Sprague-Dawley rats by i.p. injection of 2 mg/kg NMBzA twice weekly for 3 weeks. Groups receiving BBI were fed three tablets a week containing 180 mg BBI each in a mixture of Witepsol H15 and peanut butter for the duration of the experiment. The frequency of papillomas and carcinomas was reduced 45% in groups receiving BBI. Furthermore, the frequency of appearance of five separate characteristics of preneoplastic lesions was significantly reduced in the esophagi of BBI-treated animals. The most significant reduction was in the total number of lesions with simple hyperplasia. Groups receiving NMBzA and placebo tablets, containing only Witepsol H15 and peanut butter, did not display statistically significant differences in the frequency of esophageal lesions as compared to animals receiving NMBzA alone. These results demonstrate that BBI can effectively inhibit NMBzA-induced esophageal tumors when given in tablet form separate from the regular diet. PMID- 1934303 TI - Expression and induction of cytochrome P450 isozymes in hyperplastic nodules of rat liver. AB - The change of cytochrome P450 (P450) isozymes in a early stage of hepatocarcinogenesis in male F344 rats has been studied. Liver microsomes were prepared from normal rats (group 1), rats treated with diethylnitrosamine (DEN) alone, which developed no hyperplastic nodules (group 2), and rats treated with DEN plus 2-acetylaminofluorene, which developed many hyperplastic nodules (group 3). The amount and activity of P450IA1 and P450IA2 expressed in the liver were analyzed by several immunological methods using monoclonal antibodies against the P450 isozymes and a mutagenicity test. In the group 2 and 3 rats, the total amount of P450 and the amount of P450IA2 were much smaller than those in the group 1 rats, and P450IA1 was detected only from the group 3 rats. As observed by immunohistochemistry, P450IA1 was prominent in hyperplastic nodules developed in the group 3 rats, and the distribution of P450IA1+ cells in individual nodules was heterogeneous. When the rats were treated with a P450 inducer, 3-methoxy-4 aminoazobenzene or 3-methylcholanthrene, both P450IA1 and P450IA2 were induced in all groups of rats; however, the induction rates of the P450 isozymes, especially that of P450IA2, in the group 3 rats were smaller than those in the group 1 and 2 rats. The present work demonstrated that P450IA1, which is responsible mainly for detoxication of aromatic amine carcinogens, increased in level along with the development of hyperplastic nodules, whereas P450IA2, which is responsible for mutagenic or carcinogenic activation of these carcinogens, decreased in its amount and inducibility. PMID- 1934304 TI - Inhibitory effects of micronutrients on pancreatic carcinogenesis in azaserine treated rats. AB - A study was made on the effects of long-term dietary administration of beta carotene, vitamin C, vitamin E and selenium, either alone or in combination, on azaserine-induced pancreatic carcinogenesis in rats. Male Wistar rats were given two i.p. injections of 30 mg azaserine per kg body weight at 19 and 26 days of age. The rats were allocated to eight groups of 40 animals each and were fed an AIN-76 diet rich in saturated fat (20% lard), either as such or after supplementation with beta-carotene, vitamin C, beta-carotene + vitamin C, vitamin E, selenium, vitamin E + selenium, or the combination of all micronutrients investigated. Fifteen months after the last treatment with azaserine the survivors were killed. The pancreata were examined for the number and size of advanced putative preneoplastic lesions and the number of neoplasms as well. Rats maintained on a diet high in either beta-carotene, vitamin C or selenium developed significantly less atypical acinar cells nodules, adenomas and carcinomas as compared to controls. The number of tumour-bearing animals was significantly lower in the groups fed the diet high in beta-carotene or selenium. In animals of the group given a diet high in all micronutrients investigated, both the number and incidence of pancreatic tumours was lower than in all other groups. It was concluded that selenium, beta-carotene and vitamin C, alone as well as in combination, have an inhibitory effect on pancreatic carcinogenesis induced in rats by azaserine. PMID- 1934305 TI - Sex differences in the formation and persistence of DNA adducts of 2-amino-3 methylimidazo[4,5-f]quinoline (IQ) in CDF1 mice. AB - The potent food mutagen 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) is carcinogenic in the CDF1 mouse, affecting the liver, lungs and forestomach. Females are approximately twice as sensitive as males to liver tumor induction. Using 32P-postlabeling assays, the dose-response of IQ-DNA adduct formation was determined in various organs of male and female CDF1 mice after single p.o. doses of IQ. To determine the possible correlation between IQ-DNA adduct formation, persistence and tumorigenicity in target organs, young adult male and female CDF1 mice were treated with a single p.o. dose (50 mg/kg) of IQ, and IQ-DNA adducts were isolated and quantitated in liver, lungs, forestomach, small intestine and large intestine over a 24 day period. In the range of 5-50 mg IQ/kg, IQ-DNA adduct formation was related to dose in all organs examined (liver, lungs, stomach, small intestine, large intestine). Total adduct formation (expressed as relative adduct labeling, RAL) 24 h after administration was highest in the liver (6.4-6.9 x 10(-7)) with lower levels, in decreasing order, in the large intestine, small intestine (non-target organs), forestomach and lungs (target organs). In all cases the major adduct, comprising 68-79% of the total, co chromatographed with standard N-(deoxyguanosin-8-yl)-IQ. Up to three additional IQ-specific adducts could be detected. Except in the liver, adduct levels 24 h after administration of IQ were 2- to 3-fold higher in females than in males. There was no preferential retention of any one of the four adducts 1-24 days after administration of IQ. Beyond day 4 after administration, total adducts in the liver of females were approximately 2-fold higher than those in males, and the rate of removal from female lung was approximately 2-fold faster than that from male lung during the 1-24 day time period. Both these findings correspond to the known sex differences in IQ-induced tumor incidences in these organs. The higher adduct levels in non-target organs (intestines) as compared to target organs (lungs and stomach), combined with the absence of differential persistence of any individual adduct indicates that, in addition to adduct formation and persistence, other factors contribute to the target organ specificity of IQ in CDF1 mice. PMID- 1934306 TI - Induction of invasive carcinomas of the seminal vesicles and coagulating glands of F344 rats by administration of N-methylnitrosourea or N-nitrosobis(2 oxopropyl)amine and followed by testosterone propionate with or without high-fat diet. AB - The potential modifying effects of testosterone propionate (TP) and high-caloric high-fat diet (20% corn oil, HF) on rat accessory sex gland carcinogenesis were investigated. Male F344 rats were treated five times at 4-week intervals with N methylnitrosourea (MNU) i.v. or N-nitrosobis(2-oxopropyl)amine (BOP) s.c., each injection following 2 weeks pretreatment with dietary ethinyl estradiol. After completion of this carcinogen administration stage, animal groups received subcutaneous implantation of Silastic tubes filled with 40 mg TP with or without HF for 40 weeks. Carcinomas of the seminal vesicles and/or coagulating glands were induced in 5, 39 and 56% of rats given MNU alone, MNU and TP, and MNU and HF plus TP respectively. No equivalent tumors were found in rats given MNU and HF. In the BOP-treated groups, 11% of animals receiving TP but no HF diet demonstrated seminal vesicle carcinomas and 6% of rats receiving TP plus HF diet had coagulating gland carcinoma. Thus while TP exerted a strong enhancing effect on tumor growth in the seminal vesicles and coagulating glands, high caloric HF did not manifest any significant influence. PMID- 1934308 TI - Differences in DNA adduct formation between monocytes and lymphocytes after in vivo incubation with benzo[a]pyrene. AB - It was the aim of this study to compare the formation of DNA adducts in different human white blood cells. Lymphocytes and monocytes were isolated from peripheral blood by density centrifugation and by a monocyte-specific antibody linked to magnetic beads. DNA adducts were determined by 32P-postlabelling. After in vitro incubation with benzo[a]-pyrene (B[a]P) we found DNA adducts in monocytes, but not in unstimulated blood lymphocytes. Only after growth stimulation by phytohaemagglutinin did lymphocytes show an adduct pattern similar to monocytes. In contrast, B[a]P-7,8-dihydro-9,10-diolepoxide, an activated intermediate of B[a]P metabolism leads to similar DNA adducts in both cell types. When lymphocytes were incubated in the presence of B[a]P together with monocytes, then after subsequent separation lymphocytes exhibited most of the adducts found in monocytes, though to a lower extent. Our results suggest that unstimulated blood lymphocytes--which are unable to activate metabolically promutagens like B[a]P- receive the genotoxic material to form DNA adducts from other blood cells or from cells in the vessel lining. We conclude that the amount and the pattern of DNA adducts formed in whole white blood cells may be influenced considerably by a variable proportion of monocytes. PMID- 1934307 TI - Effect of deficiencies of selenium and vitamin E alone or in combination on the induction of mammary carcinogenesis by 1-methyl-1-nitrosourea. AB - Experiments were conducted to determine the dietary levels of selenium and vitamin E that could be fed chronically to induce a deficiency of one or both nutrients. It was observed that diets containing less than 0.02 mg Se/kg and 3 IU vitamin E/kg induced a deficiency without drastically altering growth performance or survival. Once established, these dietary conditions were used to investigate the effect of single or combined deficiencies of selenium and vitamin E on the promotion phase of mammary carcinogenesis induced by 1-methyl-1-nitrosourea (MNU). In the carcinogenesis experiment, 21 day old female Sprague-Dawley rats were fed a torula yeast formulated diet deficient in selenium and vitamin E until they were 50 days of age. At that time, each rat was injected i.p. with 12.5 mg MNU/kg body weight. Seven days thereafter, rats were randomly assigned to one of four treatment groups that were deficient or adequate in selenium and/or vitamin E. The experiment was terminated 30 weeks after carcinogen treatment. In comparison to rats fed the adequate diet, final cancer incidence and number were higher and cancer latency shortened in rats consuming the diet deficient in both selenium and vitamin E. Single deficiencies of either nutrient failed to significantly alter the tumorigenic response. PMID- 1934309 TI - Inhibition of 12-O-tetradecanoylphorbol-13-acetate-promoted skin tumor formation in mice by 16 alpha-fluoro-5-androsten-17-one and its reversal by deoxyribonucleosides. AB - The work of ourselves and others has demonstrated that dehydroepiandrosterone (DHEA) dispalys a broad spectrum of cancer preventive action in laboratory rodents, with little toxicity. In the two-stage skin tumorigenesis model in mice, topical application of the synthetic DHEA analog 16 alpha-fluoro-5-androsten-17 one, a more potent preventive agent than DHEA without the sex-hormonal side effects of the parent steroid, markedly inhibited promotion of 7,12 dimethylbenz[a]anthracene (DMBA)-initiated tumor development by 12-O tetradecanoylphorbol-13-acetate (TPA). DHEA is a powerful inhibitor of glucose-6 phosphate dehydrogenase (G6PDH), suggesting that its inhibiting effect in carcinogenesis may be due to a lack of NADPH and ribose-5-phosphate production for deoxyribonucleotide synthesis and subsequent DNA replication. Further evidence of a reduced NADPH and ribose-5-phosphate pool on the lowering of intracellular deoxyribonucleotide levels has been demonstrated in this paper by completely reversing the 16 alpha-fluoro-5-androsten-17-one-induced inhibition of tumor promotion by the addition of the four deoxyribonucleosides-deoxyadenosine, deoxycytidine, deoxyguanosine and thymidine--to the drinking water during the promotion period of tumorigenesis. PMID- 1934310 TI - The assay of uridine diphosphoglucose dehydrogenase activity: discrimination from xanthine dehydrogenase activity. AB - The biochemical and quantitative cytochemical assays of the activity of uridine diphosphoglucose dehydrogenase (UDPG-D) have produced perplexing results. It is now shown that the perplexity may be due to the possibility that the coenzyme (NAD) required for UDPG-D activity, may be acting as a substrate for a second dehydrogenase, namely xanthine dehydrogenase, which may utilize NAD as its substrate. The activity of UDPG-D can be distinguished selectively by the pH of its optimal activity and by decreasing the concentration of the coenzyme used in the assay. PMID- 1934311 TI - In vivo and in vitro evidence concerning the role of lipid peroxidation in the mechanism of hepatocyte death due to carbon tetrachloride. AB - Isolated rat hepatocytes exposed to CCl4 showed a stimulated formation of malonaldehyde after only 30-60 min incubation. Conversely, the onset of hepatocyte death was a relatively late event, being significant only after 2-3 h of treatment. A cause-effect relationship between the two phenomena has been demonstrated by using hepatocytes isolated from rats pretreated with alpha tocopherol. Comparable results were obtained in vivo where supplementation with alpha-tocopherol 15 h before CCl4 dosing induced a partial or complete protection against the drug's necrogenic effect, depending on the concentration of the haloalkane used. Moreover, the vitamin supplementation prevented the CCl4-induced increase of liver total calcium content, probably by blocking alterations in the liver cell plasma membranes due to lipid peroxidation. PMID- 1934313 TI - Cellular thiols in rat liver cell lines possessing different growth characteristics. AB - Thiol levels were measured in three cell lines derived from rat hepatocytes with different growth rates and degrees of tumorigenicity: IAR20 having normal epithelial morphology and no tumour forming ability; IAR6.1 being a chemically transformed malignant cell line; and IAR6.1RT7 derived from an epithelial tumour obtained after injection of IAR6.1 cells into a syngenic animal. The mean levels of GSH, GSSG, low molecular weight thiols (LMWT), macromolecular thiols (MT) and total reactive protein sulphur (TRPS), expressed as nmoles-SH mg-1 protein, were found to be 25.5, 7.5, 50.1, 114.5 and 143.6 respectively for IAR20; 37.6, 3.9, 65.4, 126.8 and 148.4 for IAR6.1; 17.2, 4.4, 52.3, 141.0 and 168.2 for IAR6.1RT7. Cultures were treated with D,L-buthionine-S,R-sulphoximine (BSO) to cause greater than 70 per cent depletion of GSH and the measurements of cellular thiols repeated. Although treatment with BSO caused a substantive decrease in the LMWT fraction, there were no major changes in macromolecular thiols or in total reactive protein sulphur. The respective mean values for LMWT, MT and TRPS (expressed as nmoles-SH mg-1 protein) were 19.4, 109.8, 136.3 for IAR20; 17.2, 119.3, 143.6 for IAR6.1; 21.6, 150.7 and 163.5 for IAR6.1RT7. It is concluded that significant differences in thiol levels exist between the three rat liver cell lines studied. However, severe acute depletion of GSH is not reflected by changes in the levels of macromolecular thiols which suggests that there is only a slow equilibrium between these two major thiol pools. PMID- 1934312 TI - Chromatin phospholipid changes during rat liver development. AB - The chromatin extracted from rat hepatocytes of different ages has been shown to contain a phospholipid fraction representing 0.47-0.59 per cent of total chromatin in newborn animals and 0.22 per cent in 45-day-old animals. No such age related differences are observed in the nuclei. The phospholipid composition of the nuclei at different ages shows a higher level of sphingomyelin and a lower level of phosphatidylserine in newborn than in adult animals. Chromatin phospholipids have a completely different composition from that of nuclei with respect to age, particularly in newborn rats, where there is a decrease in phosphatidylcholine and an increase in phosphatidylserine. PMID- 1934314 TI - A 33 kDa protein band is enhanced during long-term adaptation of EUE cells to a hypertonic medium. AB - A cell line derived from human embryonic epithelium (EUE cells) shows an enhanced expression of a 33 kDa protein when adapted to grow in a hypertonic medium containing 0.246 M NaCl (1.8 x the isotonic concentration). The maximum amount of this protein, followed by SDS-PAGE electrophoresis, was found after 4 days of adaptation; thereafter, the protein band remained fairly constant up to 30 days. When the cells were transferred back to a medium containing 0.137 M NaCl (isotonic medium), the protein pattern reverted to that of control cells. This protein is mainly localized in the cytosol, although a small part is associated with the 150,000 g pellet and needs detergents to be extracted. The molecular weight and the cellular location suggest a possible analogy with the so-called amphitropic proteins, that are known to interact with both the epidermal growth factor receptor and hydrophobic structures, such as the membrane phospholipids and the cytoskeletal components. PMID- 1934315 TI - Mitoxantrone toxicity on Ehrlich ascites tumour cells: inhibition of the transplasma membrane redox activity. AB - This study focused on the potent cytotoxic effect that mitoxantrone produces on Ehrlich ascites tumour cells. Host mice treated with mitoxantrone showed a life span three times higher than control non-treated host mice. Mitoxantrone also showed a potent cytotoxic effect on Ehrlich cells incubated in vitro for only a few hours. Studies on the effect of mitoxantrone on a plasma membrane redox system showed that mitoxantrone inhibits this activity, which is apparently related to cell proliferation. PMID- 1934316 TI - The sensitivity of synthesis of human cartilage matrix to inhibition by IL-1 suggests a mechanism for the development of osteoarthritis. AB - The damage to articular cartilage, characteristic of arthritic disease, is usually ascribed to increased degradative activity by enzymes or free radicals from locally activated cells. We propose that inhibition of matrix synthesis, and consequential impairment of the natural repair process, may be at least as important in chronic joint disease. PMID- 1934317 TI - Abnormal clumsiness in children: a defect of motor programming? AB - Abnormal clumsiness in otherwise normal children has often been associated with both perceptual and motor defects, but the cause of this problem remains unclear. This study investigated the ability of clumsy children to programme movement and to use feedback, in both the visual and kinaesthetic modalities, for movement control. Clumsy and normal children performed simple and complex movements with vision either available, or precluded. The reaction time of the clumsy children was found to be longer than that of the normal children and the movement time for the complex, but not the simple response, was found to be longer for the clumsy group. These findings were interpreted as suggesting that clumsy children experience difficulty with the programming of movement and that, as a result, they depend more heavily on feedback for movement control than do normal children. PMID- 1934318 TI - A longitudinal study of night waking in the first year. AB - A longitudinal study of the development of sleep patterns addressed the issue of continuity and change in night waking in the course of the first year. Mothers of 118 infants, who took part in a follow-up study of normal babies, completed a sleep questionnaire at 3, 6, 9 and 12 months. Regular night waking was a common characteristic throughout the first year (46% at 3 months, 39%, 58% and 55% respectively at 6, 9 and 12 months). The number of awakenings per night was a function of age. Following a decline in the number of interruptions from 3 to 6 months, an increase in night waking at age 9 months was recorded. Although the methodology does not lend itself to an objective validation of the changes in sleep-wake states, nor is it suitable for causal explanations, it is, nevertheless, important to note this profile. The increase in night waking towards the end of the first year coincides with significant socio-emotional advances which characterize this developmental stage. PMID- 1934319 TI - Two hundred school injuries presenting to an accident and emergency department. AB - Two hundred children who had been injured at school and sought hospital treatment were studied. Younger children tended to be brought to the Accident and Emergency Department later after the injuries than the older children, and one in seven of those under 15 years attended alone or without a legally acceptable guardian. Sixteen per cent of the 204 injuries were fractures, of which 70% were to the upper limbs, and 18% facial. Eighteen per cent of the injuries were lacerations requiring sutures. Younger children sustained proportionately more lacerations and fewer minor injuries such as bruises, abrasions and sprains than older children. Over half of the injuries occurred in patients' free time at school, which had been unsupervised in 51% of cases. PMID- 1934320 TI - Do 'minority' groups have special needs? Speech therapy and the Chasidic Jewish community in north London. AB - The paper addresses the issue of whether a paediatric speech therapy service can offer an adequately sensitive service to a specific community, notably the Chasidic Jewish community of north London. Fifteen parents of Jewish children were compared with 20 parents of non-Jewish children attending the same speech therapy clinic. A questionnaire was administered to both groups. The results indicate that the groups differed in the extent to which they required therapy in their own language, the Jewish group being less concerned than the non-Jewish group. The groups did not differ in the extent to which they would object to therapists on the grounds of sex or religion. When a test of significance was used, a number of differences were identified in relation to specific responses. The results are discussed in terms of the need for a culturally sensitized service. PMID- 1934321 TI - Hypotension- and endotoxin-induced alterations in calcitonin gene-related peptide: modulation by dexamethasone. AB - Plasma levels of calcitonin gene-related peptide (CGRP) were studied in anesthetized rats during and after recovery from hemorrhagic hypotension as well as following administration of bacterial endotoxin. Hypotension of 35-40 mmHg maintained for 2 hr resulted in significant (P less than .05) elevation of plasma CGRP levels. Plasma levels at 120 min of hypotension were 49.5 +/- 5.9 pg/ml, over 4-fold above average control levels (11.1 +/- 1.1 pg/ml). Plasma CGRP levels at 90 min of hypotension (20.2 +/- 2.4 pg/ml) or before were not more than 2.5 fold above control levels. Ninety minutes after the return of shed blood in the 30 min group, blood pressure (83 +/- 3 mmHg) and CGRP (17.2 +/- 2.2 pg/ml) were not different from saline controls (88 +/- 3 mmHg and 15.1 +/- 1.7 pg/ml CGRP). However, if hypotension was maintained for 120 min before the return of shed blood, blood pressure following 90 min recovery was significantly lower (59 +/- 5 mmHg) and CGRP levels significantly higher (39.2 +/- 5.6 pg/ml) than saline control values (82 +/- 5 mmHg and 19.5 +/- 2.7 pg/ml). Dexamethasone treatment of the 120 min hypotension group when shed blood was returned resulted in CGRP values not different from saline treated, but hypotension persisted. Administration of bacterial endotoxin (16.7 mg/kg) to anesthetized rats caused significant elevations (P less than .05 vs. saline treatment at 3 hr) in plasma CGRP levels from aorta (82.2 +/- 5.0 pg/ml), vena cava (79.4 +/- 12.9), and portal vein (117.7 +/- 29 pg/ml) compared to levels in saline-treated control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934322 TI - Role of bradykinin in ovine endotoxemia. AB - We determined if the cardiopulmonary response to endotoxin (LPS) is mediated by bradykinin (BK). Sheep (n = 30) were prepared for chronic study with cardiopulmonary catheters, and chronic lung lymph fistulae. They were divided into the following study groups: A) BK infusion; B) LPS; C) LPS with angiotensin converting enzyme inhibitor (ACEI); D) ACEI alone; E) LPS with BK antagonist. Cardiac index and mean arterial pressure fell (6.9 +/- 0.4 to 5.3 +/- 0.3 L/min/m2 and 93 +/- 4 to 72 +/- 3 mmHg, respectively), and pulmonary lymph flow increased (10.5 +/- 3.0 to 17.8 +/- 4.3 ml/hr) during BK infusion. Addition of ACEI during BK infusion reduced the amount of BK necessary to induce a comparable response (125 to 2 micrograms/kg/hr). Administration of ACEI to LPS animals did not significantly alter their cardiopulmonary responses. BK antagonist did not change the response to LPS. Although the kallikrein-kinin pathway is believed to be activated during the septic response, our data do not lend support for the hypothesis that bradykinin is an important mediator of the cardiopulmonary changes. PMID- 1934323 TI - In vitro phosphatidylcholine peroxidation mediated by activated human neutrophils. AB - Activated human polymorphonuclear leukocytes (PMNs) mediated peroxidation of dilinoleoyl phosphatidylcholine (DPLC) liposomes. Concentration-response effects were demonstrated for both PMNs and DLPC in the system studied. Chelated iron facilitated peroxidation threefold. Superoxide dismutase variably inhibited peroxidation, but never completely. Although O2-. synthesis ceased 30-40 min after PMN stimulation, lipid peroxidation continued for an additional 30-60 min, suggesting that PMNs may initiate peroxidation which subsequently becomes autocatalytic. Enhanced PMN-mediated DLPC peroxidation was noted in acidic media. Separation of DLPC reaction products by high pressure liquid chromatography demonstrated the de novo appearance of conjugated diene species. Preliminary specific ion monitoring mass spectroscopy analysis of gas chromatography fractions of reaction products (derivatized to fatty acid methyl esters/trimethylsilane hydroxyl ethers) indicated that PMN-generated oxyradicals resulted in production of conjugated 9- and 13-hydroperoxy DLPC derivatives. These results illustrate directly how activated PMNs may participate in host autoinjury by mediating phospholipid peroxidation. PMID- 1934325 TI - Amrinone during porcine intraperitoneal sepsis. AB - Seven Yucatan minipigs with chronic, severe intraperitoneal sepsis were given amrinone i.v. (loading dose of 0.75 mg/kg, followed by continuous infusion of 10, 20, 40, and 80 micrograms/kg/min) during the hyperdynamic phase of sepsis. Hemodynamic variables and oxygen utilization, delivery, and extraction were recorded throughout the study. Pulmonary capillary wedge pressure was kept constant to ensure a fixed ventricular filling pressure. Intravenous amrinone modestly augmented cardiac index without altering heart rate. Mean systemic and pulmonary arterial pressures decreased. Systemic and pulmonary vascular resistance fell significantly (P less than 0.05). Amrinone did not significantly alter oxygen utilization or oxygen extraction, although oxygen delivery increased (P less than .05). During the hyperdynamic phase of sepsis in this animal model, amrinone elicits vasodilatation with a modest improvement in stroke volume index. Consequently, cardiac output and oxygen delivery increased modestly. Because of its vasodilating properties and small salutary effects, amrinone is not an optimal first-line medication for hemodynamic stabilization during hyperdynamic sepsis. PMID- 1934324 TI - Effects of RA642, a new central pressor agent, on renal sympathetic nerve activity and blood pressure during hemorrhagic shock in rabbits. AB - This experiment was designed to evaluate effects of RA642, a pyrimido-pyrimidine derivative, on renal nerve activity (RNA), mean blood pressure (MBP), central venous pressure (CVP), and heart rate (HR) during hemorrhagic shock in anesthetized rabbits. Hemorrhagic hypotension of 30 mmHg was induced by rapid bleeding and was controlled by a servocontrolled pump. Following the onset of hemorrhagic hypotension, RNA response showed a triphagic pattern: an initial increase in RNA and a secondary increase followed by a profound decline in RNA. In all animals, decreases in RNA occurred within approximately 30 min after bleeding in association with significant decreases in heart rate. When RNA fell to near noise level, the effects of RA642 (0.25 mg/kg, iv, N = 10), physiological saline (N = 7), epinephrine (10 micrograms/kg, iv, N = 6), and dopamine (10 micrograms/kg, iv, N = 5) were then tested. Intravenous injection of saline produced no significant improvements of hypotension nor of reduction in RNA. However, treatment with RA642 produced a significant increase in MBP simultaneously with an increase in RNA. During the hypovolemic hypotensive phase, tachycardia did not occur after the treatment with RA642. Twenty-five minutes after the retransfusion, MBP and RNA in the RA642-treated group were at significantly higher levels than in the saline group. HR did not significantly change with the RA642 treatment after the retransfusion. In another six animals, when RNA fell to near noise level, epinephrine caused a transient increase in MBP and HR. Ventricular arrythmias occurred in 50% of epinephrine-treated animals. However, the level of MBP as improved by epinephrine was significantly lower than that by RA642 at 25 min after the retransfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934326 TI - Awake porcine model of intraperitoneal sepsis and altered oxygen utilization. AB - We have characterized an awake swine model of septic shock. Hemodynamic, serum chemistry, and oxygen metabolism parameters were compared between eight septic and five sham animals. Eight male Yucatan miniature swine, weighing 20-28 kg, were anesthetized and catheters were placed in the pulmonary artery, external jugular, and the carotid artery. On day 2, 1.1-4.0 x 10(10) cfu Escherichia coli/kg were administered via an intraperitoneal catheter. Hemodynamic parameters were monitored hourly for 6 hours in awake animals. The animals were then placed back into the animal holding facility for clinical observation until the 24 hour post infusion measurements were taken. Septic animals were initially hypodynamic, with a decrease in cardiac index (CI) from a baseline value of 152.8 +/- 24.8 to 87.9 +/- 17.8 ml/kg/min (P less than .05) and an increased systemic vascular resistance index (SVRI) from a control value of 48.1 +/- 9.5 to 65.0 +/- 16.7 dynes*sec*cm-5/kg. At 24 hours post infusion, the animals were hyperdynamic with the CI increased to 211.0 +/- 27.2 ml/kg/min (P less than .05) and a decreased SVRI to 30.64 +/- 3.9 dynes*sec*cm-5/kg (P less than .05). Oxygen utilization (VO2) increased during sepsis from 6.6 +/- 0.8 to 8.1 +/- 0.8 ml/kg/min at 6 hours (P less than .05) and remained elevated at 24 hours at 7.7 +/- 0.4 (P less than .05). Increased oxygen consumption was attained with an increase in oxygen extraction (O2 ext) from 0.34 +/- 0.03 to 0.56 +/- 0.07 (P less than .05) during the first 6 hours of sepsis. At 24 hours, increased oxygen utilization was maintained by high oxygen delivery state. Significant alterations in serum chemistries in conjunction with post mortem evidence of multiple organ system failure were observed. Mortality on or before 4 days post infusion was 50% and positive blood cultures were obtained in 38% of the animals studied. This awake swine model serves as an excellent model to study metabolic pathophysiology and the treatment of septic shock. PMID- 1934327 TI - Therapeutic intervention in a rat model of adult respiratory distress syndrome: II. Lipoxygenase pathway inhibition. AB - The present study was designed to investigate the role of 5-lipoxygenase (5LO) metabolites in an endotoxin (LPS)-induced model of the adult respiratory distress syndrome (ARDS) in the rat. The therapeutic value of two 5LO inhibitors and a specific LTB4 and a LTD4 receptor antagonist were examined. Rats were treated 1 hr prior to administration of aerosolized LPS. Rats were either unexposed (n = 11), or pretreated with vehicle sham (n = 63), 50 mg/kg phenidone t.i.d. (n = 7, n = 10 for assessment of mortality), 30 mg/kg SK&F 103842 b.i.d. (n = 6), 50 mg/kg SK&F 106203 t.i.d. (n = 11), or 5 mg/kg SK&F 107324 b.i.d. (n = 6) 1 hr prior to the administration of aerosolized endotoxin (LPS, 7 mg/kg) or phosphate buffered saline (PBS, n = 22). Twenty-four hours later, blood samples were collected for hematologic evaluation and after wet lung weight was determined, broncho-alveolar lavage (BAL) was performed to measure cells counts and total protein (TP). 5LO inhibition and LTD4 receptor antagonism reduced LPS-induced mortality to zero compared to 35% in rats pretreated with vehicle sham. Pretreatment with the LTD4 receptor antagonist attenuated the LPS-induced increased in wet/dry lung weight (W/D) whereas 5LO inhibition reduced TP increases. Both 5LO inhibition and LTD4 receptor antagonism attenuated the LPS induced BAL erythrocyte increase. The LPS-induced thrombocytopenia was attenuated by phenidone, the 5LO receptor antagonist. We conclude that the increased microvascular permeability was associated with the formation of 5LO products since 5LO inhibition lessened the severity of the LPS-induced increase in W/D and TP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934328 TI - Therapeutic intervention in a rat model of adult respiratory distress syndrome: III. Cyclooxygenase pathway inhibition. AB - Current strategies for the treatment of ARDS have been unsuccessful in reducing mortality. In the present study, we have evaluated the role of cyclooxygenase (CO) products in a rat model of ARDS by testing naproxen, indomethacin, ibuprofen, and a thromboxane A2 (TXA2) receptor antagonist (SK&F 96148). Rats were treated 1 hr prior to endotoxin (LPS) exposure and 24 hr later, survival, body weight changes, wet/dry lung weight (W/D), total protein content (TP) of the bronchoalveolar lavage (BAL) fluid, and total erythrocyte and differential leukocyte counts of the BAL fluid were measured. In addition, the following hematologic measurements were taken: hemoglobin (Hb), hematocrit (Hct), circulating erythrocyte, differential leukocyte, and platelet counts. Treatment with the TXA2 receptor antagonist reduced mortality to zero after 24 hr after LPS administration. Other compounds had no significant effect on LPS-induced mortality. Pretreatment with CO inhibitors or the TXA2 receptor antagonist attenuated the LPS-induced increase in TP and W/D. Although all compounds tended to reduce the LPS-induced increase in BAL erythrocytes, only the TXA2 receptor antagonist did so significantly. The LPS-induced increase in BAL neutrophil counts was significantly reduced by 30 mg/kg ibuprofen, but not by the other compounds. In fact, the TXA2 receptor antagonist actually exacerbated BAL neutrophil counts, but diminished the peripheral neutrophilia and lymphopenia induced by LPS. None of the CO inhibitors tested significantly affected LPS induced hematologic responses. We conclude that by virtue of its protection against LPS-induced mortality, the TXA2 receptor antagonist was the most effective compound in this model. However, it did cause certain negative side effects such as increased pulmonary inflammation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934330 TI - Evolution of rhythms during periodic stimulation of embryonic chick heart cell aggregates. AB - During periodic stimulation of spontaneously beating chick heart cell aggregates, there is often an evolution of coupling patterns between the stimulator and the aggregate action potential. For example, at rapid stimulation frequencies, a rhythm that is initially 1:1 (stimulus frequency:aggregate frequency) can evolve to other rhythms such as 5:4 and 4:3. Time-dependent effects generated during periodic stimulation are characterized by three types of experiments to determine 1) the effect of periodic stimulation on the intrinsic cardiac beat rate (overdrive suppression), 2) the effect of periodic stimulation on the phase resetting properties of the aggregate, and 3) the time-dependent changes in the coupling patterns between the stimulator and the aggregate during periodic stimulation. The protocols involved variations in the duration and rate of periodic stimulation. A mathematical model is developed in the form of a two dimensional finite difference equation based on the data from experiments 1 and 2. The model is used to predict the data generated by experiment 3. There is good correspondence with the experiments in that the theory reproduces complex transitions between various rhythms and displays irregular rhythms similar to those observed experimentally. These results have implications for the evolution of cardiac arrhythmias such as atrioventricular heart block and modulated parasystole. PMID- 1934329 TI - Conjugated desferoxamine attenuates hepatic microvascular injury following ischemia/reperfusion. AB - Iron-dependent oxy radicals have been implicated in reperfusion injury. Although the iron chelator desferoxamine (DFO) is beneficial, its hemodynamic effects and short vascular retention limit its use in vivo. We tested whether DFO conjugated to a high-molecular-weight starch might ameliorate in vivo hepatic microvascular injury without adverse side effects following 120 min of ischemia. Prior to reperfusion, conjugated DFO (100 mg/kg), vehicle (Veh), or saline (I/R) was administered. After 90 min of reperfusion, blood was collected for serum transaminase determination (ALT; U/liter), and fluorescein-albumin was injected to label perfused microvessels, which were quantified in frozen sections by a point-count technique. Tissue edema was estimated by wet to dry weight ratios (W/D). Reperfusion results in hepatocyte injury (rise in ALT and W/D) and a 30% loss of perfused microvessels. Intravenous administration of conjugated DFO produces no significant change in systemic hemodynamics, whereas both ALT and tissue edema were decreased by approximately 50%. Moreover, perfused microvessels were restored virtually to nonischemic control levels. Enhanced perfusion and attenuated cell injury with DFO suggest that microvascular failure and resultant cell death are mediated, at least in part, by iron-dependent mechanisms in reperfusion. PMID- 1934331 TI - Endothelial, not hemodynamic, differences are responsible for preferential leukocyte rolling in rat mesenteric venules. AB - At the onset of the inflammatory process, leukocytes roll along venular but not arteriolar walls before they firmly attach and emigrate. To test whether differences in hydrodynamic flow conditions are responsible for the preferential occurrence of leukocyte rolling in venules, we varied wall shear rate, gamma w, between 30 and 2,000 sec-1 by selective micro-occlusion of side branches in venules and arterioles (diameter, 20-37 microns) of the exposed mesentery of anesthetized rats. In venules, 39% (range, 6-77%) of all passing leukocytes were found interacting with the endothelium (rolling), whereas this fraction was only 0.6% in arterioles. The fraction of rolling leukocytes in venules decreased from 49 +/- 13% at gamma w less than 100 sec-1 (N = 12) to 24 +/- 13% at gamma w greater than 400 sec-1 (N = 12). Mean leukocyte rolling velocity in venules increased with gamma w, but the most frequent rolling velocity class was 20-40 microns/sec at all shear rates. In arterioles, even prolonged (up to 90 minutes) conditions of reduced flow (gamma w less than 150 sec-1) did not induce leukocyte rolling. Radial distribution of freely flowing leukocytes not different in arterioles and venules. The data indicate that hemodynamic factors are not responsible for the difference of leukocyte adhesion between arterioles and venules. The venular endothelium appears to be specialized to support leukocyte adhesion during inflammation. This finding correlates with reports on preferential expression of various endothelial-leukocyte adhesion molecules on venular endothelial cells. PMID- 1934332 TI - Characteristics of giant cells and factors related to the formation of giant cells in myocarditis. AB - Giant cell myocarditis is a serious and frequently fatal inflammatory heart disease of which the etiology remains unknown. In the present study, we investigated the origin of multinucleated giant cells in myocarditis with the use of an experimental model. We also examined the factors relating to the formation of giant cells in myocarditis. Severe myocarditis characterized by the appearance of multinucleated giant cells was induced in Lewis rats by immunization with cardiac myosin in complete Freund's adjuvant. Two types of giant cells, foreign body giant cell-like and myocytelike, were observed in this myocarditis. Immunohistochemical studies revealed that both types of multinucleated giant cells were stained with OX42 and ED1 (macrophage markers) and were not stained with anti-desmin antibody and HHF35 (markers for muscle fibers). Therefore, it is likely that multinucleated giant cells in this myocarditis are derived from macrophages. During the course of the disease, the appearance of multinucleated giant cells was restricted to a period corresponding with the fulminant phase of inflammation. When the severity of the disease was modulated by immunization with various doses of the antigen, multinucleated giant cells appeared only in severe myocarditis after inoculation of a large dose of the antigen. Administration of immunoadjuvants also affected the formation of giant cells. Most of the rats injected with cardiac myosin in complete Freund's adjuvant developed giant cell myocarditis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934333 TI - Left ventricular function depends on previous beat ejection but not previous beat pressure load. AB - Previous beat contraction history, in which the performance of the left ventricle on any one beat is influenced by the mechanical events of the previous beat, may be important in the beat-to-beat regulation of left ventricular performance in the intact cardiovascular system. Prior studies of this phenomenon have established that mechanical events of the previous beat influence the function of the current beat, but it is not known whether the important mechanical influence is exerted by previous beat ejection or previous beat pressure. In addition, the magnitude of the effect of previous beat contraction history on left ventricular performance is unknown. To make these determinations, we performed experiments in six isolated rabbit left ventricle preparations buffer perfused at 30 degrees C. Left ventricular pressure and volume were controlled precisely with a servo controlled linear motor system. After steady-state ejecting conditions were established by clamping left ventricular ejection pressure at 60% of peak isovolumic pressure, single test beats, which were pressure clamped at 40%, 60%, 80%, and 100% of peak isovolumic pressure, were introduced and followed by an isovolumic reference beat. As the level of pressure clamp decreased from 100% to 40%, developed pressure on the isovolumic beat following the single test beats increased from 139 +/- 15 (mean +/- SD) to 151 +/- 13 mm Hg. Similarly, peak positive left ventricular dP/dt increased from 1,718 +/- 209 to 1,864 +/- 181 mm Hg.sec-1 (both p less than 0.01). Multiple regression analysis showed that this increase in left ventricular function was related to previous beat ejection but not to previous beat pressure load or relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934334 TI - Relation between ventricular and myocyte remodeling with the development and regression of supraventricular tachycardia-induced cardiomyopathy. AB - Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction. Termination of SVT appears to reduce LV size and improve function. However, changes in myocyte structure and morphology that accompany the development and regression of SVT-induced cardiomyopathy have not been studied. Accordingly, we measured LV function using echocardiography and catheterization in three groups of six pigs each: 3 weeks of atrial pacing (SVT; 240 beats/min), 4-week recovery from SVT (PST), and sham-operated controls. At each of these three end points, isolated myocyte dimensions and nuclear number were measured using fluorescence, and the volume percent of myocytes and myofibrils was computed from tissue sections using stereological techniques. SVT resulted in reduced LV fractional shortening (15 +/- 3% versus 31 +/- 2%, p less than 0.05), increased end-diastolic dimension (5.6 +/- 0.8 versus 3.8 +/- 0.2 cm, p less than 0.05), and no change in mass (2.6 +/- 0.1 versus 2.6 +/- 0.2 g/kg, p = NS) compared with controls. Myocyte length significantly increased with SVT (171 +/- 9 versus 109 +/- 11 microns, p less than 0.05), without significant changes in cell width (28 +/- 2 versus 26 +/- 2 microns). Nuclear number did not change with SVT; however, nuclear area/myocyte area significantly increased compared with controls (9.5 +/- 0.8 versus 8.7 +/- 0.8 x 10(-2), p less than 0.05). The volume percent of myocytes within the ventricular wall and the volume percent of myofibrils within myocytes decreased with SVT compared with controls (72 +/- 3% versus 80 +/- 3% and 45 +/- 5% versus 63 +/- 4%, respectively, p less than 0.05), with no change in total myocyte volume (54.2 +/- 2.7 versus 54.3 +/- 1.8 microns3 x 10(12)). In the PST group, LV fractional shortening returned to control values; however, there was persistent dilatation (end-diastolic dimension: 4.2 +/- 0.1 cm, p less than 0.05), and LV hypertrophy developed (3.3 +/- 0.3 g/kg, p less than 0.05). Increased myocyte length (158 +/- 5 microns, p less than 0.05) and width (33 +/- 2 microns, p less than 0.05) were observed in the PST group. The volume percent of myocytes and myofibrils returned to control values, with total myocyte volume significantly increased in the PST group compared with the control and SVT groups (74.5 +/- 2.6 microns3 x 10(12), p less than 0.05). In addition, the number of nuclei per myocyte in the PST group significantly increased from control values (5.1 +/- 0.1 versus 4.0 +/- 0.1, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1934335 TI - Remodeling of coronary vessels during aging in purebred beagles. AB - We compared six young (1 year) and six senescent (11 years) purebred beagles to determine the effects of aging on the coronary microvasculature. The hearts were perfusion-fixed in vitro, and myocardial specimens were subjected to microscopic image analysis. Absolute left ventricular mass increased by 55% with age, while cardiocyte cross-sectional area increased by 10% and 30% in the midmyocardium and endomyocardium, respectively. Although capillary numerical density was lower in the senescent dogs (16% in midmyocardium and 19% in endomyocardium), volume density was similar in the two groups because capillary diameter increased significantly with age in both regions. Capillary length density was reduced by 27% with age in the endomyocardium of the old beagles. Wall/lumen ratios of arterioles of three size classes (less than or equal to 15, 16-25, and 26-50 microns) were found to be nearly identical for the two age groups. Mean arteriolar diameter increased within the smallest size class in both ventricular regions. In contrast, a twofold or greater increase in wall thickness with age occurred in the left anterior descending coronary artery and its first branch, which was mainly due to expansion of the medial interstitium. The connective tissue fraction of the myocardium was significantly higher in the senescent than in the young in the epimyocardium and midmyocardium but not in the endomyocardium. These data provide evidence for three conclusions regarding aging of coronary vessels in beagles. First, a decline in capillary length density is limited to the endomyocardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934336 TI - Spontaneous tachyarrhythmias after cholinergic suppression in the isolated perfused canine right atrium. AB - Atrial fibrillation occurs spontaneously after bradycardia induced by acetylcholine infusion or vagal stimulation. To determine the mechanism of initiation of this tachyarrhythmia, we infused acetylcholine (5 ml, 10(-3.5) M) into Krebs-Henseleit-perfused isolated canine right atria (n = 10). Unipolar electrograms were recorded from 250 sites simultaneously during control rhythms, pacing (cycle length = 300 msec) with and without acetylcholine, and recovery of spontaneous activity. Activation sequence maps were constructed from each recording. Stable spontaneous rhythm was present in all preparations during control conditions. Activation sequence maps, recorded during continuous pacing with and without acetylcholine, demonstrated no dromotropic changes due to the acetylcholine. Focal asynchronous recovery of spontaneous activity was initiated from different sites, resulting in bigeminal or trigeminal premature depolarizations in 41 of 73 cases after infusion of acetylcholine. A reentrant tachyarrhythmia was initiated in 24 of 41 cases by the closely coupled recovery beats (A1A2 = 100 +/- 37 msec; A2A3 = 97 +/- 27 msec). The reentry was initiated by interaction of the premature impulse with regions of functional block that were a result of the cholinergically induced dispersion of refractoriness. All the tachyarrhythmias terminated spontaneously, and stable spontaneous control rhythms returned. In conclusion, the data suggest that the premature depolarizations that initiate the reentrant tachyarrhythmia are caused by the asynchronous recovery of multiple right atrial pacemakers accompanied by variable entrance block at the later depolarizing sites. PMID- 1934337 TI - Diminished endothelium-derived relaxing factor activity in an experimental model of chronic heart failure. AB - Abnormalities in vasomotor tone, including enhanced vasoconstriction at rest and diminished vasodilation in response to various stimuli, develop as a consequence of chronic heart failure. This study was undertaken to evaluate whether a specific local mechanism, namely endothelium-derived relaxing factor (EDRF) activity, might be impaired in an experimental model of chronic heart failure. Segments of thoracic aorta (TA) and pulmonary artery (PA) were isolated from a group of rats that had hemodynamic evidence of heart failure 10 weeks after ligation of the left coronary artery (n = 25) and from a group of sham-operated control rats (n = 18). Both endothelium-dependent and endothelium-independent vascular responses were assessed by exposing arterial segments to increasing concentrations of agonists. All studies were performed in the presence of 10 microM indomethacin to avoid the influence of vasoactive prostanoids. The dose response curve for EDRF-mediated relaxation to acetylcholine was shifted rightward in rats with heart failure, and the concentrations of acetylcholine required to achieve 50% maximal relaxation (EC50) were increased compared with those of control rats in both TA and PA segments. Additionally, the dose-response curve for relaxation to ADP was shifted rightward with significantly increased EC50 in PA segments from rats with heart failure. In contrast, EDRF-mediated relaxation to the calcium ionophore A23187 was similar in the groups. Endothelium independent relaxation to nitroglycerin was slightly increased in TA but not PA segments in the heart-failure group. Basal EDRF activity, as assessed by the increase in force after exposure to hemoglobin, was diminished in PA segments from rats with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934338 TI - Effects of epinephrine on firing characteristics of two functionally different types of carotid baroreceptors. AB - Sympathetic stimulation and catecholamine exposure have been shown to sensitize the arterial baroreceptors, but the extent or importance of this effect is not known. We performed this study to investigate the effects of sympathetic feedback on the carotid sinus baroreceptors, specifically examining the effect of the stimulation on the two different functional types of baroreceptors characterized in an earlier study. The existence of two baroreceptor function-response curves has suggested that the roles of the two functionally different baroreceptors may not be the same. If true, the effects of epinephrine exposure on baroreceptor firing characteristics may contribute to differential roles played by each baroreceptor type in the control of blood pressure. Single-fiber baroreceptor activity from a vascularly isolated carotid sinus was recorded during slow increases in carotid sinus pressure before and during exposure to epinephrine (10(-8) to 10(-6) M). Baroreceptor firing characteristics were determined from function curves plotting carotid sinus pressure versus nerve activity, with curve fitting analysis of the hyperbolic type I and sigmoidal type II baroreceptor curves used to obtain threshold (Pth) and saturation (Psat) pressures, threshold (Fth) and saturation (Fsat) firing rates, and sensitivity (slope) for each baroreceptor before and during epinephrine exposure. The possible mechanisms of observed changes were examined using our previously published baroreceptor computer model. Epinephrine exposure was found to significantly increase sensitivity, Fth, and Fsat of both types of baroreceptors, with a relatively greater effect on type I sensitivity and on type II Fth and Fsat. Epinephrine also was found to increase the level of spontaneous discharge for type II baroreceptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934339 TI - Effects of neuropeptide Y on cell length and membrane currents in isolated guinea pig ventricular myocytes. AB - Direct effects of neuropeptide Y were studied in left ventricular myocytes isolated from guinea pigs. Contraction was measured as the change in unloaded cell length using a photodiode array. Action potentials were elicited at 1 Hz in current-clamp mode, and membrane currents were measured using a switch-clamp amplifier with 2 M-KCl microelectrodes. At concentrations of 10(-6) M and above, neuropeptide Y reduced contraction in a concentration-dependent fashion. The reduction in contraction by the peptide was proportionately greater in the presence of isoproterenol, and the increase in contraction caused by isoproterenol was completely inhibited by 10(-6) M neuropeptide Y. In response to neuropeptide Y, action potential duration was shortened, and the time course of the shortening was similar to that of the reduction in contraction. Under voltage clamp, 1 x 10(-5) M neuropeptide Y reduced peak L-type calcium current by 32% and shifted the myocyte current-voltage relation during a slow ramp in a manner that suggested a reduction in the background rectifier K+ current. The effects of the peptide on membrane currents were greatly attenuated by preincubation of the cells with pertussis toxin (100 ng/ml). We conclude that neuropeptide Y reduces developed shortening, action potential duration, L-type calcium current, and background rectifier current in single guinea pig ventricular myocytes and that these effects are mediated, at least in part, via membrane G proteins. PMID- 1934340 TI - Concentration-dependent effects of protein kinase C-activating and -nonactivating phorbol esters on myocardial contractility, coronary resistance, energy metabolism, prostacyclin synthesis, and ultrastructure in isolated rat hearts. Effects of amiloride. AB - An extensive investigation of the cardiac actions of phorbol esters and the potential role of the Na(+)-H+ exchanger in those actions was carried out using isolated rat hearts. Sixty minutes of perfusion with 10(-9) M phorbol 12 myristate 13-acetate (PMA) or 10(-8) M phorbol 12,13-dibutyrate (PDBu) produced marked cardiac dysfunction associated with depressed contractility, coronary constriction, and elevated resting tension, the latter being particularly evident with PMA. These effects were also associated with disturbances in tissue levels of energy metabolites manifested primarily by a reduction in ATP and an elevation in lactate. Furthermore, both phorbols produced a sustained stimulation of the release of 6-ketoprostaglandin F1 alpha (6-keto PGF1 alpha), the hydrolysis product of prostacyclin (prostaglandin I2). Amiloride, an inhibitor of the Na(+) H+ exchanger, significantly attenuated the loss in contractility and elevation in coronary pressure as well as the stimulated release of 6-keto PGF1 alpha but was without effect on elevations in resting tension or on changes in energy metabolites. Increasing concentrations of PMA or PDBu 10-fold resulted in a much more rapid and severe (greater than 80% loss in contractile function after 30 minutes) effect that was nonetheless qualitatively identical to that seen with the lower concentrations of phorbol. However, the effects were not prevented by amiloride. Surprisingly, 4 alpha-phorbol 12,13-didecanoate (alpha-PDD, 10(-6) M), which does not activate protein kinase C, was found to be a potent inhibitor of cardiac function (greater than 80% loss in contractility and 50% increase in resting tension) after 30 minutes of perfusion, although these effects were not associated with changes in levels of energy metabolites or with elevations in coronary pressure. Similarly, none of the actions of this compound were attenuated by amiloride. In contrast to the sustained effects of other phorbols on 6-keto PGF1 alpha release, the effect of alpha-PDD was transient (less than 10 minutes). In all hearts studied, the marked depression in contractile function caused by all phorbol esters occurred in the absence of any ultrastructural changes. 4 alpha-Phorbol (10(-6) M), which does not activate protein kinase C, was without effect on any parameter studied. Our results demonstrate very complex effects of phorbol esters on numerous parameters of cardiac function, including an amiloride-sensitive component that occurs at low concentrations. The latter observation suggests the involvement of Na(+)-H+ exchange activation, possibly occurring as a consequence of protein kinase C stimulation, in mediation of the effects of phorbol esters at low concentrations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1934341 TI - Role of ATP-sensitive potassium channels in coronary microvascular autoregulatory responses. AB - The purpose of the present study was to test the hypothesis that ATP-sensitive potassium channels mediate autoregulatory vasodilatation of coronary arterioles in vivo. Experiments were performed in 23 open-chest anesthetized dogs. Coronary arterial microvascular diameters were directly measured with fluorescence microangiography using an intravital microscope and stroboscopic epi-illumination synchronized to the cardiac cycle. A mild coronary stenosis (perfusion pressure = 60 mm Hg), a critical coronary stenosis (perfusion pressure = 40 mm Hg), and complete coronary artery occlusion were produced with an occluder around the left anterior descending coronary artery in the presence or absence of glibenclamide (10(-5) M, topically), which inhibits ATP-sensitive potassium channels, or of vehicle. During topical application of vehicle (0.01% dimethyl sulfoxide), there was dilatation of small (less than 100 microns diameter) arterioles during reductions in perfusion pressure (percent change in diameter: 6.7 +/- 1.5%, 11.7 +/- 3.5%, and 10.4 +/- 5.1% during mild stenosis, critical stenosis, and complete occlusion, respectively). In the presence of glibenclamide, arteriolar dilatations during coronary stenoses and occlusions were abolished. Glibenclamide did not affect responses of arterioles greater than 100 microns. Glibenclamide did not alter microvascular responses to nitroprusside. These data suggest that ATP-sensitive potassium channels play an important role in determining the coronary microvascular response to reductions in perfusion pressure. PMID- 1934342 TI - Myocyte mitotic division in the aging mammalian rat heart. AB - To determine whether myocyte mitotic division occurs in the adult mammalian heart and whether this cellular process is affected by aging, we measured the percentage of myocyte nuclei showing metaphase chromosomes in myocytes isolated from the left and right ventricles of rats at 8-12, 19-24, and 28-32 months after birth. Metaphase chromosomes were found at all ages in both ventricles. However, from 8-12 to 28-32 months, the fraction of nuclei exhibiting metaphase chromosomes increased 6.3-fold and 2.3-fold in the left and right ventricles, respectively. Thus, myocyte cellular hyperplasia is present in the adult and aging myocardium as a compensatory mechanism to regenerate tissue mass and recover function, which are lost with the progression of life and senescence. PMID- 1934343 TI - Rapid accumulation of elastin and collagen in the aortas of sheep in the immediate perinatal period. AB - While characterizing developmental changes in aortic wall composition in sheep, we observed very rapid accumulation of elastin and collagen in the immediate perinatal period. Thoracic aortic elastin content increased by 41%, and collagen content increased by 49% in approximately 1 week, between 140 days gestation and 3 days postpartum (term = 145 days). Even larger changes were observed in the abdominal aorta. Elastin content increased by 66%, and collagen increased by 57%. The pronounced increase in wall tissue accumulation near birth preceded a marked postnatal increase in arterial pressure. We propose that this elastin and collagen accumulation is a preadaptive response in preparation for the later increase in pressure. The prenatal and postnatal events that initiate this synthesis and accumulation are not known. We also found that, in the 3 weeks after this initial rapid increase, accumulation of elastin and collagen was markedly reduced in the abdominal, but not the thoracic, aorta. This latter finding may be linked to the dramatic decrease in flow through this vessel that results from the loss of the placental circulation. Finally, we observed that relatively high smooth muscle cell replication rates in the abdominal aorta postpartum resulted in no net DNA accumulation. This finding indicates that cell turnover plays an important role in postnatal arterial growth and development. PMID- 1934344 TI - Determination of local myocardial electrical activation for activation sequence mapping. A statistical approach. AB - Electrical activation sequence mapping requires accurate identification of local activation, but because extracellular recordings do not exclusively reflect local events, complex electrograms may be difficult to interpret. In such cases, the assignment of local activation is subject to error that could affect interpretation of the resulting activation maps. The purpose of this investigation was to develop an approach that would provide quantitative indexes of error in the determination of local activation. An electrode array with 64 closely spaced unipolar electrodes was used to record from the left ventricular surface during open heart surgery. Electrograms with multiple deflections were recorded from four patients with scarred myocardium; two other patients with normal myocardial function served as controls. Each of 784 deflections was scored on the basis of three features: evidence for propagation, the configuration of the bipolar signal, and the effect of changing from the chest to an average reference. Local activation was considered probable if evidence for all three features was present and improbable if none of the three features was present. Deflections that were ambiguous with respect to this standard were excluded. Of over 30 test variables analyzed, the three with the greatest power to discriminate signals due to local activation from those due to distant activity were 1) a linear combination of the extracellular potential plus the ratio of the second derivative and the extracellular potential, 2) the second derivative, and 3) the minimum (greatest negative) first derivative. For each of these variables, the threshold value providing the greatest performance was identified by the maximum quality of efficiency, an index of agreement. This statistical approach provides an objective basis for determining local activation and provides a quantitative assessment of error that could enhance interpretation of electrical activation sequence maps. PMID- 1934345 TI - EMD 53998 sensitizes the contractile proteins to calcium in intact ferret ventricular muscle. AB - EMD 53998 (a thiadiazinone) is an inotropic drug that produces a pronounced increase in the Ca2+ sensitivity of the contractile proteins in skinned cardiac fibers. The present study was undertaken to determine whether this effect on Ca2+ sensitivity could explain the increase in tension observed in intact ventricular muscle. The experiments were performed on isolated ferret papillary muscles that had been microinjected with aequorin to measure the intracellular Ca2+ concentration. Force and intracellular Ca2+ concentration were monitored before, during, and after application of EMD 53998. EMD 53998 (5 microM) increased developed tension by 230%; aequorin light transients increased by only 85%, and this increase was reduced and became insignificant in the presence of agents that prevent catecholamine release. When a similar increase in developed tension was produced by elevation of extracellular calcium, the aequorin light transients increased by 240%. Thus, EMD 53998 produces a substantial Ca2+ sensitization in intact ventricular muscle, and this can explain most of its inotropic effect. In addition, EMD 53998 caused a small prolongation of the time course of contraction and a small reduction of the time course of the aequorin light transient. A computer model is described that shows that both these effects can be explained by the effect of EMD 53998 on Ca2+ sensitivity. At much higher concentrations, EMD 53998 also caused an increase in resting tension. EMD 53998 is the first agent for which much of the inotropic effect in intact cardiac muscle can be accounted for by increased Ca2+ sensitivity of the contractile proteins. Inotropic agents with this mechanism of action cause increased force production with much less increase in the intracellular Ca2+ transients than conventional agents and, therefore, increase the energy efficiency of the myocardium and are less likely to cause Ca(2+)-activated arrhythmias. PMID- 1934346 TI - Specific block of the anti-ischemic actions of cromakalim by sodium 5 hydroxydecanoate. AB - The potassium channel activators cromakalim and pinacidil were recently shown to have anti-ischemic properties in isolated globally ischemic rat hearts. The effects of two reported blockers of ATP-sensitive potassium channels, glibenclamide (glyburide) and sodium 5-hydroxydecanoate, on the anti-ischemic efficacy of cromakalim were determined in this model. Buffer-perfused rat hearts were subjected to 25 minutes of ischemia followed by 30 minutes of reperfusion. Pretreatment of these hearts with 60 microM cromakalim significantly decreased indexes of contractile function but caused a significant improvement of postreperfusion function and a significant decrease in release of lactate dehydroxygenase and in end-diastolic pressure. Pretreatment with glibenclamide at concentrations that reversed the preischemic effects of cromakalim (0.05 and 1.0 microM) also significantly reversed its postischemic protective effects. Sodium 5 hydroxydecanoate (100 and 300 microM) had no effect on the preischemic (negative inotropic) effects of cromakalim but completely reversed its cardioprotective effects. Sodium 5-hydroxydecanoate did not reverse the cardioprotective effects of the calcium entry blocker diltiazem. In phenylephrine-contracted rat aorta, glibenclamide (0.1-10 microM) inhibited cromakalim-induced relaxation, whereas sodium 5-hydroxydecanoate (10-1,000 microM) had no effect. Similarly, the ability of cromakalim to shorten cardiac action potential duration in guinea pig papillary muscle and to increase outward whole-cell potassium currents in isolated myocytes was inhibited by glibenclamide, whereas sodium 5 hydroxydecanoate was without effect. Thus, both glibenclamide and sodium 5 hydroxydecanoate inhibited the effects of cromakalim after reperfusion; however, sodium 5-hydroxydecanoate, unlike glibenclamide, had no effect in nonischemic preparations. These results suggest that sodium 5-hydroxydecanoate is an ischemia selective inhibitor of ATP-sensitive potassium channels. PMID- 1934347 TI - Experimental model of effects on normal tissue of injury current from ischemic region. AB - An ischemic myocardial region contains cells with a depolarized resting membrane potential. This depolarization leads to an intercellular current flow between the ischemic region and the surrounding normal myocardial cells, which has been termed an "injury current." We have devised an experimental model system in which an isolated rabbit ventricular cell is electrically coupled to a model depolarized cell to evaluate the effects of this injury current on the electrical properties of a normal ventricular cell. We found that the action potential duration of the isolated cell could be reversibly altered by varying the coupling resistance such that the action potential duration was shortened by high values of coupling resistance but could be considerably prolonged by lower resistance coupling. We did not observe automaticity in the isolated cell as a consequence of coupling to the depolarized model. The changes in action potential duration were accompanied by alterations in the frequency at which the isolated cell could respond to repetitive stimuli. In addition, the depolarization of the isolated cell produced by the electrical coupling led to a significant increase in the cellular excitability. This last effect may be of particular importance in understanding the mechanisms for origination of arrhythmias in the border zone of myocardial ischemia. PMID- 1934348 TI - Increased oxygen cost of contractility in stunned myocardium of dog. AB - Recent studies have shown that myocardial oxygen consumption does not proportionally decrease with the deterioration of contractile function in stunned myocardium. To investigate this disproportion, we studied the end-systolic pressure-volume relation and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA, a measure of total mechanical energy) in stunned hearts. In the VO2-PVA relation, VO2 can be divided into PVA dependent and PVA-independent fractions. In excised cross-circulated dog left ventricles, a 15-minute normothermic global ischemia followed by 60-120 minutes of reperfusion significantly decreased the ventricular contractility index (Emax) by approximately 40%, but the PVA-independent VO2 did not significantly decrease. Oxygen cost of PVA, defined as the slope of the VO2-PVA relation, was slightly decreased in stunned hearts. Restoration of the depressed Emax to the preischemic control level by calcium infusion increased the PVA-independent VO2 to 137 +/- 27% of control level (p less than 0.01). Oxygen cost of contractility, defined as the slope of the relation between PVA-independent VO2 and Emax, increased from 0.0011 +/- 0.0003 to 0.0023 +/- 0.0005 ml O2.ml.mm Hg-1.beat-1 per 100 g myocardium in control and stunned hearts, respectively (p less than 0.01). From these new finding, we conclude that the unchanged VO2, despite the depressed contractility in stunned myocardium, is mainly due to the increased oxygen cost of contractility. PMID- 1934349 TI - Preservation of endothelial cells in excised rat carotid arteries. Effects of transmural pressure and segment length. AB - When arteries are excised, they collapse and shorten spontaneously, which can result in damage to the endothelium. To determine if an intact endothelial cell layer could be preserved in excised vessels, we isolated and cannulated rat carotid artery segments (in situ length, Lis, 10-20 mm) at both ends while maintaining both transmural pressure (70 mm Hg) and Lis, while either transmural pressure or Lis, or after allowing vessel collapse and shortening (n = 4 vessels per treatment). After each treatment, vessel segments were perfused with fixative and stained with AgNO3 to visualize endothelial cells. The amount of endothelial cell loss was quantified using stereological analysis of video microscopic images of the luminal surface. Results demonstrated that maintenance of both Lis and transmural pressure minimized endothelial cell denudation (1.6 +/- 0.9%); permitting the vessel to collapse and shorten resulted in the greatest loss of endothelial cells (59.4 +/- 13.2%); and maintenance of either pressure or Lis resulted in intermediate endothelial cell loss (13-30%). We conclude that the spontaneous collapse and shortening that normally accompany the excision of arterial segments result in substantial endothelial cell loss, which can be virtually eliminated with the maintenance of transmural pressure and vessel segment length. These findings have implications for surgical and experimental procedures requiring intact endothelium. PMID- 1934350 TI - Cooperative effects due to calcium binding by troponin and their consequences for contraction and relaxation of cardiac muscle under various conditions of mechanical loading. AB - A mathematical model for the regulation of mechanical activity in cardiac muscle has been developed based on a three-element rheological model of this muscle. The contractile element has been modeled taking into account the results of extensive mechanical tests that involved the recording of length-force and force-velocity relations and muscle responses to short-time deformations during various phases of the contraction-relaxation cycle. The best agreement between the experimental and the mathematical modeling results was obtained when a postulate stating two types of cooperativity to regulate the calcium binding by troponin was introduced into the model. Cooperativity of the first type is due to the dependence of the affinity of troponin C for Ca2+ on the concentration of myosin crossbridges in the vicinity of a given troponin C. Cooperativity of the second type assumes an increase in the affinity of a given troponin C for Ca2+ when the latter is bound by molecules neighboring troponin. PMID- 1934351 TI - Polymorphonuclear neutrophil contribution to induced tolerance to bacterial lipopolysaccharide. AB - The objective of this study was to investigate mechanisms by which polymorphonuclear neutrophils (PMNs) contribute to the tolerance induced by repeated lipopolysaccharide (LPS) injections. Tolerance was developed by daily intraperitoneal injections of sublethal doses of LPS for 4 days (LPS-tolerant group); controls were not pretreated (LPS-control group). Both groups were challenged with 9 mg/kg i.v. Escherichia coli LPS, a dose that resulted in 25% survival in LPS-control rats compared with 100% survival in LPS-tolerant rats. LPS injection caused an initial neutropenia in both groups. The neutropenia persisted throughout the experiment in LPS-control rats, whereas in LPS-tolerant rats the circulating PMN count increased dramatically; after 6 hours, the PMN count was 16-fold higher than that in LPS-control rats. Activation of circulating PMNs, PMN adhesion to nylon fibers, and tumor necrosis factor/cachectin activity were all increased in control rats given LPS. In contrast, LPS-tolerant rats had low activation of circulating PMNs, no trend for PMN adhesion to nylon fibers, and markedly reduced tumor necrosis factor activity. To determine whether neutropenia was associated with a trapping of PMNs in the microcirculation, we used a carbon perfusion technique 6 hours after LPS injection and examined histological sections of the myocardium. All of the arterioles and venules in both groups contained carbon; only capillaries showed evidence of obstruction. A significantly higher percentage of obstructed capillaries was observed in LPS control rats than in LPS-tolerant rats. Obstruction of capillaries was consistently associated with trapped leukocytes. We conclude that PMN cytotoxicity induced by LPS involves microcirculatory entrapment and activation of PMNs. Repeated LPS pretreatment reduces dramatically circulating PMN activation and adhesion and is associated with an elevated circulating PMN count, a low degree of microvascular plugging, and survival after a normally lethal dose of LPS. PMID- 1934352 TI - Force-velocity relation and myosin light chain phosphorylation in bovine coronary arterial smooth muscle. AB - We have investigated in bovine left ventricular coronary arteries the relation between the biochemical regulatory event of myosin light chain phosphorylation and the mechanical events of isometric stress and isotonic shortening, under conditions of stimulation by depolarization (65 mM KCl) or receptor occupancy (2 microM 5-hydroxytryptamine [5-HT]). At rest, levels of light chain phosphorylation were 0.07 +/- 0.01 mol phosphate/mol light chain. Maximal values were significantly different for KCl (0.42 +/- 0.02 mol phosphate/mol light chain at 1 minute) and 5-HT stimulation (0.58 +/- 0.01 mol phosphate/mol light chain at 30 seconds). Increases in light chain phosphorylation preceded isometric stress development, and values remained elevated at approximately 0.35 mol phosphate/mol light chain for up to 2 hours with both KCl and 5-HT. The sites of phosphorylation were identical for KCl and 5-HT at 2 hours. Maximal stresses for each stimulus were also maintained for 2 hours. Values of maximum velocity of shortening (Vo in muscle lengths [ML]/sec), obtained from the force-velocity relation, did not change significantly between 1 minute and 2 hours with KCl (0.070 +/- 0.008 ML/sec at 1 minute and 0.056 +/- 0.007 ML/sec at 2 hours, p greater than 0.2). However, during 5-HT stimulation, Vo declined significantly (0.053 +/- 0.006 ML/sec at 1 minute and 0.032 +/- 0.003 ML/sec at 2 hours, p less than 0.025). The relation between Vo and light chain phosphorylation was different for KCl and 5-HT, indicating that factors in addition to myosin light chain phosphorylation may modulate smooth muscle shortening velocity. PMID- 1934353 TI - Troponin T isoform expression in humans. A comparison among normal and failing adult heart, fetal heart, and adult and fetal skeletal muscle. AB - The expression of troponin (Tn) T, a thin-filament regulatory protein, was examined in left ventricular myocardium from normal and from failing adult human hearts. The differences in isoform expression between normal and failing myocardium led us to examine the ontogenic expression of TnT in human striated muscle. Left ventricular samples were obtained from patients with severe heart failure undergoing cardiac transplantation and normal adult organ donors. Fetal muscle was obtained from aborted fetuses after 14-15 weeks of gestation, and adult skeletal muscle was obtained from surgical biopsies. Western blots of normal and failing adult heart proteins demonstrated that two isoforms, TnT1 and TnT2, are expressed in different amounts, with TnT2 being significantly greater in failing hearts (p less than 0.004). Western blots of two-dimensional gels of these proteins resolved two predominant spots of both TnT1 and TnT2 and several minor TnT species. Alkaline phosphatase treatment converted the two major spots of each isoform into the single more basic spots. A comparison of the ATPase activities and the TnT2 percentage of total TnT in individual failing and normal adult hearts demonstrated an inverse and negative relation (r = 0.7, p less than 0.02). In the fetal heart, four TnT isoforms were found, two of which had the same electrophoretic mobilities as the adult cardiac isoforms TnT1 and TnT2. Fetal skeletal muscle expressed two of the four fetal cardiac TnT isoforms, one of which comigrated with adult cardiac TnT1. These cardiac isoforms were expressed in low abundance in fetal skeletal muscle relative to seven fast skeletal muscle TnT isoforms. No cardiac isoforms were present in adult skeletal muscle. Because many etiologies caused heart failure in the transplant patients, we propose that the disease-associated increased expression of the TnT isoform TnT2 is an adaptation to the heart failure state and a partial recapitulation of the fetal expression of cardiac TnT isoforms. PMID- 1934354 TI - Identification and functional significance of troponin I isoforms in neonatal rat heart myofibrils. AB - We investigated the mechanism(s) responsible for differences in the effects of acidic pH on Ca2+ activation of the activity of adult and neonatal rat heart myofilaments. Studies on preparations of myofilaments reconstituted with adult troponin-tropomyosin (Tn-Tm) and either adult or neonatal thick filaments indicated that the difference in effect of acidic pH is related to differences in Tn-Tm and not other myofilament proteins. Immunoblotting analysis showed that development of the rat heart myofibrils is associated with isoform switching from slow skeletal TnI to cardiac TnI and from a slow mobility isoform of TnT (TnT1) to a faster Mr isoform (TnT2. Expression of slow skeletal TnI was associated with a relative insensitivity of myofilament Ca2+ activation to deactivation by acidic pH. Moreover, the effect of acidic pH on Ca2+ activation of ATPase activity of soleus myofibrils, which contain cardiac TnC and slow skeletal TnI, was essentially the same as the effect of acidic pH on rat cardiac myofibrils in the early neonatal period. Neonatal myofilaments also contained a relative abundance of a set of polypeptides copurifying with the thin filaments. We have identified these proteins as histones. The relative amount of histones among a variety of preparations from different species was not correlated with the pH sensitivity of myofibrillar Ca2+ activation. Shifts in TnT isoforms among these species were also not correlated with an altered response to acidic pH. Our data provide evidence in support of the hypothesis that the relative insensitivity of neonatal myofilament activity to acidic pH is due to the presence of slow skeletal TnI in the thin-filament regulatory complex. PMID- 1934355 TI - Effects of phorbol esters on pial arteriolar diameter and brain production of prostanoids in piglets. AB - We determined the effects of phorbol 12,13-dibutyrate (PDB), which activates protein kinase C, on pial arteriolar diameter and cerebrospinal fluid (CSF) prostanoid levels in newborn pigs. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy. In addition, CSF was sampled from under the window, and prostanoid levels (prostaglandin [PG] E2, 6-keto-PGF1 alpha, PGF2 alpha, and thromboxane B2) were determined by radioimmunoassay. Diameter and CSF prostanoid levels were determined during application of artificial CSF containing no drugs and during application of 10(-8), 10(-7), and 10(-6) M PDB. We also determined effects of 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), a phorbol ester that does not activate protein kinase C, and dimethyl sulfoxide, the vehicle for the phorbol esters, on pial arteriolar diameter and CSF prostanoid levels. Initial diameters were 100-200 microns. At 10(-8)-10(-6) M, PDB progressively constricted pial arterioles and increased CSF levels of prostanoids; the other phorbol ester and dimethyl sulfoxide had no such effects. Baseline arteriolar diameter was 147 +/- 17 microns (mean +/- SEM), and diameter was 140 +/- 17 microns at 10(-8) M PDB, 120 +/- 18 microns at 10(-7) M PDB (p less than 0.05), and 108 +/- 14 microns at 10(-6) M PDB (p less than 0.05) (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934356 TI - Structural and functional origins of suppressed acetylcholine vasodilation in diabetic rat intestinal arterioles. AB - This study evaluated the possible impairments to endothelium-mediated vasodilation by structural and functional properties of the intestinal arterioles in adult (20-21-week-old) rats after 8-11 days or 7-8 weeks of streptozotocin induced diabetes. Arteriolar intravascular pressures and luminal diameters were simultaneously measured during iontophoretic application of acetylcholine, bradykinin, and nitroprusside to the outer vessel wall, and passive diameter pressure relations were obtained during maximal vasodilation. Microvascular pressures and circumference-passive wall tension relations were similar between all diabetic and normal rats and did not appear to significantly influence vasodilation. Both acute and chronic hyperglycemia were associated with near complete suppression of acetylcholine-induced vasodilation in large arterioles, and the threshold dose for vasodilation of intermediate arterioles was approximately 10-fold higher in diabetic rats. In both diabetic groups, dilatory responses to nitroprusside were normal, and in chronically diabetic rats, the relative vasodilation in response to various doses of bradykinin was equivalent to that found in normal rats. These observations indicate that a very specific deficit of acetylcholine-induced endothelium-derived relaxing factor action rapidly develops in intestinal arterioles of diabetic rats, but the arteriolar wall mechanical properties, cGMP-mediated muscle relaxation, and endothelial release of the bradykinin-stimulated relaxing factor are not compromised after 7 8 weeks of chronic hyperglycemia. PMID- 1934357 TI - Signal requirements for the generation of CD4+ and CD8+ T-cell responses to human allogeneic microvascular endothelium. AB - Microvascular endothelium has been implicated as a major target in the rejection of vascularized allografts. In an attempt to dissect the stepwise generation of the T-cell-mediated immune response to microvascular endothelial cells (ECs), we analyzed the requirements for the two major T-cell subsets, CD4+ and CD8+, in the triggering of proliferative and cytotoxic responses to allogeneic ECs in vitro. Results demonstrate that resting ECs are unable to stimulate a functional response by purified T, CD4+, and CD8+ cells in the absence of costimulatory signals. T cells and CD8+ cells develop both proliferative and cytotoxic anti-EC responses by the addition of as little as 2 units/ml interleukin-2, 10 units/ml interleukin-1, or irradiated monocytes autologous to the responder lymphocytes, whereas only autologous monocytes are capable of triggering CD4+ T-cell precursors to proliferate and become anti-EC-specific effector cytotoxic T lymphocytes. CD8+ cell-mediated anti-EC cytotoxicity is directed toward allogeneic major histocompatibility complex (MHC) class I determinants on ECs and involves recognition by the CD3/T-cell receptor complex and the CD8 molecule on the effector T cells. CD4+ cells can be driven to proliferate, produce interleukin-2, and become anti-EC-specific cytotoxic T lymphocytes despite the lack of detectable membrane MHC class II determinants on the target cells. Chloroquine inhibition experiments demonstrate that autologous monocytes/macrophages are required by CD4+ T-cell precursors for the processing of EC-derived alloantigens and their subsequent presentation in the context of self-MHC molecules. These results are in agreement with the adoptive transfer experiments in experimental allograft models and suggest that the coordinate engagement of cells of the CD4, CD8, and monocyte/macrophage series is more effective than the individual cell subsets in the PMID- 1934358 TI - Contractile deactivation and uncoupling of crossbridges. Effects of 2,3 butanedione monoxime on mammalian myocardium. AB - We investigated the effects of 1 and 3 mM 2,3-butanedione monoxime (BDM, diacetyl monoxime) on excitation and contraction of cardiac muscle in several types of preparations at various levels of organization. We selected a concentration of BDM that was not expected to affect sarcolemmal calcium flux and action potential duration in cardiac tissue. Two indicators were used to record intracellular calcium. Aequorin, a bioluminescent calcium indicator, was used in studies with ferret papillary muscle preparations, and fura-2, a fluorescent calcium indicator, was used in studies with guinea pig cardiac myocytes. In both cases, addition of BDM resulted in a reduction of peak intracellular calcium released from the sarcoplasmic reticulum and a reduction of peak twitch force. The duration of the action potential of isolated myocytes was slightly abbreviated in the presence of BDM. In studies on the calcium current in the myocytes, addition of BDM was associated with reduced calcium current at any potential. Peak calcium current was reduced by 7.9 +/- 1% in the presence of BDM. In tetanized ferret papillary muscles, BDM reduced maximal calcium-activated force by 30 +/- 5% and increased the calcium ion concentration required for half-maximal force by 0.1 +/ 0.01 microM. The Hill coefficient was reduced from 5.00 +/- 0.11 to 3.40 +/- 0.20. Maximal shortening velocity of ferret papillary muscles was increased in the presence of BDM from 1.55 +/- 0.24 to 2.04 +/- 0.33 mm/sec. Ca2+ binding to troponin C in skinned fiber preparations from guinea pig, bovine, and canine hearts was unaffected by addition of up to 10 mM BDM. Our results indicate that BDM affects both calcium availability and responsiveness of the myofilaments to Ca2+. Uncoupling of contractile activation from excitation may also result from altered crossbridge kinetics. PMID- 1934359 TI - Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits. AB - The endothelium-derived relaxing factor is rapidly inactivated by superoxide radicals, and atherosclerotic vessels generate excess radical species. We tested the hypothesis that an imbalance between intrinsic superoxide dismutase (SOD) activity and the generation of superoxide radicals in atherosclerotic arteries may result in augmented inactivation of endothelium-derived relaxing factor. Vascular SOD was increased in normal and cholesterol-fed (1% cholesterol for 4 months) rabbits approximately twofold by treatment with polyethylene-glycolated SOD (PEG-SOD; 41,000 units/kg/day i.m.) for 1 week. Aortic rings from these animals and nontreated control and atherosclerotic rabbits subsequently were studied in organ chambers. Endothelium-dependent relaxations to acetylcholine and the calcium ionophore A23187 were improved by PEG-SOD in atherosclerotic but not in normal rabbits. PEG-SOD pretreatment did not alter endothelium-independent relaxations to nitroprusside. Thus, treatment with PEG-SOD can partially restore impaired endothelium-dependent relaxation of atherosclerotic arteries. We conclude that generation of oxygen-derived radicals likely contributes to endothelial dysfunction of atherosclerotic arteries. PMID- 1934360 TI - Dynamics of the background outward current of single guinea pig ventricular myocytes. Ionic mechanisms of hysteresis in cardiac cells. AB - Subthreshold potentials are thought to be mediated by time-independent, "passive" background currents. In this study, we show that the background current-voltage (I-V) relation of guinea pig ventricular myocytes is changed significantly by repetitive stimulation, in such a way that cell excitability becomes enhanced. Myocytes were used for whole-cell voltage-clamp experiments. A voltage-clamp ramp (100 mV/sec) to -50 mV was applied from a holding potential of -100 mV. Subsequently, a train of square voltage-clamp pulses to +10 mV (duration, 300 msec; interpulse interval, 300 msec) was delivered from a holding potential of 85 mV. A new ramp was applied again immediately after the train, and the resulting I-V curve was compared with that obtained before the train. Pulsing displaced the I-V relation to the right, the zero-current point becoming 1-2 mV less negative, and increased the degree of inward-going rectification. These changes were insensitive to tetrodotoxin (30 microM); disappeared during superfusion with cobalt (2 mM), verapamil (22 microM), or ryanodine (5 microM); and could not be mimicked by agonists of the protein kinase C system. In the presence of cesium (8 mM), pulsing still displaced the I-V curve to the right. However, the linear portion of the curve became steeper after the train. Subtraction of the cesium-sensitive current from control revealed that, although the zero-current point remained constant, the I-V relation showed a stronger inward-going rectification after pulsing. In accordance with these results, we have demonstrated hysteresis of excitability in ventricular myocytes. We conclude that the observed changes are mediated by an increase in intracellular calcium, which leads to an increase in rectification of IK1, as well as to activation of another membrane-conductance system, perhaps the Na-Ca exchange or the Ca(2+) activated, nonselective current. PMID- 1934361 TI - Reactivity of canine isolated epicardial collateral coronary arteries. Relation to vessel structure. AB - To study the relation between structure and vascular reactivity in mature coronary collateral arteries, we prepared 17 dogs with a casein occluder near the origin of the circumflex coronary artery. At least 24 weeks later, we examined the reactivity of surface collateral arteries (approximately 500 micron i.d.) to a range of constrictor and dilator agents and compared them with normal left anterior descending coronary arteries of similar size branching away from the collateral zone. Pairs of normal and collateral arteries 2 mm long were mounted in a double-vessel myograph for isometric force recording. Arteries were contracted by K+ (124 mM) or by cumulative addition of endothelin-1 (1-100 nM) or U46619 (1-300 nM), a thromboxane A2 mimetic drug. In each case, the collateral vessels contracted to approximately half the force generated by the normal arteries. When partially contracted by K+ (25-30 mM), the collateral vessels had a greater range of relaxation and similar sensitivity to acetylcholine, sodium nitroprusside, and cromakalim compared with normal arteries. Morphological and morphometric analyses revealed that the collateral arteries had thickened adventitia, thinner media, ruptured internal elastic laminae, and a thick neointima lined by endothelium. Theoretical calculations of luminal area were made for isotonic conditions in response to constrictor stimuli. Despite the poor contractility of the collateral arteries, the neointimal luminal encroachment further reduced the lumen to zero, an exaggerated response compared with normal arteries. Coronary collateral arteries are thus compromised flow conduits that may play a role in vasospastic angina. PMID- 1934362 TI - Single cardiac vagal fiber activity, acute myocardial ischemia, and risk for sudden death. AB - Experimental and clinical evidence indicates that high risk for sudden death is significantly correlated with post-myocardial infarction depression in two "markers" of vagal activity, heart rate variability and baroreflex sensitivity. The present experiments were designed to answer some of the questions generated by those findings. In 33 anesthetized cats, the neural activity of single cardiac vagal efferent fibers was recorded in control conditions and after injection of phenylephrine (n = 33), before and during a 1-hour coronary artery occlusion (CAO) (n = 17), and before and after removal of the left stellate ganglion (n = 16). In the first minute after CAO, vagal activity increased by 35% from 1.66 +/- 0.37 to 2.57 +/- 0.62 impulses/sec (p less than 0.01); despite a slight decline, it remained for the entire CAO above the control values, to which it returned after CAO release. Of 17 cats, ventricular fibrillation occurred in nine (susceptible) and eight survived (resistant). Resistant and susceptible cats had different reflex vagal responses to CAO. Whereas the resistant cats had a 48% (p less than 0.01) increase by the second minute of CAO, susceptible cats had no change (-18%, p = NS) in vagal activity. These differences were independent of blood pressure changes. The increase in vagal efferent activity in response to the blood pressure rise induced by phenylephrine (baroreceptive reflex) was more marked in the resistant cats compared with the susceptible cats (+246 +/- 66% versus +80 +/- 14%, p less than 0.025). Just before the injection of phenylephrine, vagal activity was not different between resistant and susceptible cats (1.58 +/- 0.35 versus 1.48 +/- 0.30 impulses/sec, p = NS). In 16 cats, left stellectomy increased cardiac vagal efferent activity by 75% (p less than 0.01), and the reflex vagal activation secondary to phenylephrine was further enhanced (from 2.2 +/- 0.4 to 4.7 +/- 0.7 impulses/sec, p less than 0.001). These data demonstrate that 1) cardiac vagal efferent activity increases in response to acute myocardial ischemia--much more so among the animals destined to survive, 2) before CAO, susceptible and resistant animals can be identified by the vagal response to blood pressure increase (assessed clinically by baroreflex sensitivity) and not by tonic vagal activity (assessed clinically by heart rate variability), and 3) the findings with left stellectomy support the hypothesis that vagal activity decreases after myocardial infarction because of an increase, secondary to abnormal stretch of the cardiac mechanoreceptors, in cardiac sympathetic afferent traffic, which exerts a tonic restraint on vagal outflow. PMID- 1934363 TI - Troponin I isoform expression in human heart. AB - Troponin I is the inhibitory component of troponin, the thin filament regulatory complex in striated muscle. Separate genes encode cardiac-specific fast and slow skeletal-specific isoforms of this protein. We have previously described gene switching from the slow skeletal to the cardiac troponin I mRNA expression in developing rat heart. The purpose of this work was to characterize the expression of the different troponin isoforms in the human heart. Human cardiac and slow skeletal troponin I cDNA probes were obtained by screening an adult cardiac cDNA library and by Taq polymerase amplification of RNA from an infant's heart, respectively. We found that the cardiac troponin I isoform is tissue-specific in its expression in normal adult tissues. RNA blot analysis of cardiac ventricular RNA from infants with congenital heart disease and from an adult with cardiomyopathy revealed expression of human cardiac troponin I in all analyzed specimens. In addition, we found expression of slow skeletal troponin I mRNA and protein in infant hearts but no detectable mRNA expression in the adult heart. We conclude that troponin I isoforms are developmentally regulated in the human heart by a mechanism similar to that in the rat heart. PMID- 1934364 TI - Hyperpolarization and relaxation of resistance arteries in response to adenosine diphosphate. Distribution and mechanism of action. AB - Membrane hyperpolarization appears to be an important mechanism of vasodilation induced by many pharmacological and endogenous vasodilators. The objective of the present study was to determine the mechanisms of vasodilation induced by ADP, and endogenous vasodilator, in various resistance arteries isolated from the rabbit. ADP hyperpolarized (12-15 mV) and relaxed mesenteric and skeletal muscle resistance arteries. The hyperpolarization was abolished by glibenclamide, an inhibitor of ATP-sensitive potassium channels. Glibenclamide inhibited part of the ADP-induced relaxations of these arteries; thus, a portion of the relaxation appears to result directly from the change in membrane potential. Hyperpolarizations and relaxations to low concentrations of ADP (less than 0.3 microM) were abolished by removal of the endothelium, but responses to higher concentrations of ADP were partially independent of the endothelium. ADP did not hyperpolarize but did relax small-diameter middle cerebral arteries, and glibenclamide had no effect on these ADP-induced relaxations. Relaxations of small cerebral arteries to all concentrations of ADP were endothelium dependent. These studies support the hypothesis that activation of ATP-sensitive potassium channels is an important general mechanism of vasodilation, including responses of resistance arteries. However, this generalization may not apply to small pial arteries of the rabbit. PMID- 1934365 TI - Congenital heart disease in adults. A new cardiovascular subspecialty. PMID- 1934366 TI - G proteins in the heart. A redundant and diverse transmembrane signaling network. PMID- 1934367 TI - Usefulness of transesophageal echocardiography in assessment of aortic dissection. AB - BACKGROUND: The value of transesophageal echocardiography in the assessment of patients with aortic dissection was studied. METHODS AND RESULTS: Group 1 (34 patients) represented all patients studied at our institution with this technique in whom aortic dissection was proven by aortography, surgery, or autopsy. Group 2 (27 patients) represented all patients studied with this technique at our institution in whom aortic dissection was excluded by aortography. Transesophageal echocardiography made a correct diagnosis of aortic dissection in 33 of 34 patients (sensitivity, 97%; specificity, 100%). It also correctly demonstrated the type of dissection in all 29 patients with aortographic or surgical proof. On the other hand, computed tomography scanning, performed in 24 of 34 patients in group 1, made a correct diagnosis in only 67% of patients and misclassified the type of dissection in 33%. Transesophageal echocardiography correctly identified involvement of the coronary arteries by aortic dissection in six of seven patients as well as absence of both left and right coronary artery involvement in 10 patients with aortic dissection. This technique was also useful in detecting communications between the true and false lumens, presence of thrombi in the false lumen, and, in two patients, localized dissection rupture with formation of a false aneurysm. In both groups 1 and 2, transesophageal echocardiography correctly identified patients with moderate to severe aortic regurgitation. CONCLUSIONS: Transesophageal echocardiography is very useful in the assessment of aortic dissection. PMID- 1934368 TI - Predictors of in-hospital mortality after DC catheter ablation of atrioventricular junction. Results of a prospective, international, multicenter study. AB - BACKGROUND: The Catheter Ablation Registry was the first international, multicenter, prospective study of the safety and efficacy of catheter ablation. METHODS AND RESULTS: From August 1987 through March 1990, the study comprised 136 patients in whom only DC energy was used in attempted production of third-degree atrioventricular block to treat uncontrollable supraventricular tachycardias. Eight patients died during hospitalization for ablation. In seven (5.1%), the ablation may have contributed to their deaths. Causes of death included ventricular fibrillation (five patients, three with polymorphic ventricular tachycardia), progressive heart failure (one patient), and respiratory failure (two patients, one dying after resuscitation from ventricular fibrillation). Compared with survivors, patients who died were more likely to have had prior aborted sudden death (38% versus 2%, p less than 0.05), congestive heart failure (88% versus 22%, p less than 0.001), cardiomyopathy (50% versus 16%, p less than 0.05), lower baseline systolic blood pressure (106 versus 138 mm Hg, p less than 0.001), prolonged baseline and postablation corrected QT interval (p less than 0.01), and markedly reduced ejection fraction (27% versus 52%, p less than 0.001). Ablation successfully produced third-degree atrioventricular block in 88% of the patients who died and in 83% of survivors. CONCLUSIONS: Catheter ablation of the atrioventricular junction with DC energy carries a significant, previously unrecognized risk of death (5.1%), particularly from lethal arrhythmias, when applied to patients with severe left ventricular dysfunction. Great care should be taken in these seriously ill patients to guard against postablation ventricular arrhythmias. PMID- 1934370 TI - Transvenous coronary ultrasound imaging. A novel approach to visualization of the coronary arteries. AB - BACKGROUND: Catheter-based ultrasound is a new imaging modality to examine endovascular detail in the coronary circulation. This technique requires direct placement of the catheter in the arterial segment of interest. METHODS AND RESULTS: We examined the feasibility of a less invasive approach by imaging the coronary arterial circulation by using a 5F (30 MHz) imaging catheter placed in the cardiac venous system. Using simultaneous fluoroscopy, we studied anesthetized closed-chest dogs (n = 6) and human subjects undergoing right heart catheterization (n = 11). After cannulation of the coronary sinus, the circumflex coronary artery (Cx) was visualized from the great cardiac vein (GCV), and on advancing the catheter into the anterior interventricular vein (AIV), the left anterior descending artery (LAD) was identified. Where artery and vein were parallel to each other, circular cross-sectional images of the coronary artery were obtained, whereas oblique and transverse orientation of artery to vein produced ellipsoid images or long-axis images. In the dogs, ultrasound-determined cross-sectional area of the coronary arteries (4.81 +/- 0.18 mm2) correlated closely with angiography (4.77 +/- 0.21 mm2) (r = 0.91, p less than 0.001). In humans, the Cx was readily visualized from the GCV in all subjects but because of anatomic variability, the LAD was seen less consistently from the AIV (73%). There was significant correlation between ultrasound-determined cross-sectional areas of the coronary arteries (8.25 +/- 0.34 mm2) with those from angiography (8.59 +/- 0.3 mm2) (r = 0.82, p = 0.001) in humans. In all subjects, the ultrasound transducer could be safely advanced into the AIV to the cardiac apex. Limitations of the technique include ultrasonic penetration problems, caused in part by the large size of human coronary veins and variability in artery-vein relations. CONCLUSIONS: We conclude that transvenous imaging of coronary arteries with intravascular ultrasound is a less invasive, promising new approach to the study of structure and morphology in the coronary vasculature. PMID- 1934369 TI - Three-dimensional reconstruction of human coronary and peripheral arteries from images recorded during two-dimensional intravascular ultrasound examination. AB - BACKGROUND: Intravascular ultrasound provides high-resolution images of vascular lumen, plaque, and subjacent structures in the vessel wall; current instrumentation, however, limits the operator to viewing a single, tomographic, two-dimensional image at any one time. Comparative analysis of serial two dimensional images requires repeated review of the video playback recorded during the two-dimensional examination, followed by a "mind's eye" type of imagined reconstruction. METHODS AND RESULTS: Computer-based, automated three-dimensional reconstruction was used to generate a tangible format with which to assess and compare a "stacked" series of two-dimensional images. Three-dimensional representations were prepared from sequential images obtained during intravascular ultrasound examination in 52 patients, 50 of whom were studied before and/or after percutaneous revascularization. Conventional two-dimensional ultrasound images were acquired by means of a systematic, timed pullback of the ultrasound catheter through the respective vascular segments. Images were then assembled in automated fashion to create a three-dimensional depiction of the vessel lumen and wall. Computer-enhanced three-dimensional reconstructions were generated in both sagittal and cylindrical formats. The sagittal format resulted in a longitudinal profile similar to that obtained during angiographic examination; in contrast to angiography, however, the sagittal reconstruction offered 360 degrees of limitless orthogonal views of the plaque and arterial wall as well as the vascular lumen. The cylindrical format yielded a composite view of a given vascular segment, and a hemisected version of the cylindrical reconstruction enabled en face inspection of the reconstructed luminal surface. Sagittal reconstructions facilitated analysis of dissections and plaque fractures resulting from percutaneous revascularization, and the hemisected cylindrical reconstructions enhanced analysis of endovascular prostheses. CONCLUSIONS: This preliminary experience demonstrates that computer-based three-dimensional reconstruction may further augment the use of intravascular ultrasound in assessing vascular pathology and guiding interventional therapy. PMID- 1934371 TI - Effects of intravenous adenosine on antegrade refractoriness of accessory atrioventricular connections. AB - BACKGROUND: Several groups have suggested the use of intravenous adenosine or adenosine triphosphate in the diagnosis of regular broad complex tachycardias. However, the short half-life of these agents has precluded assessment of their effects on refractoriness of accessory connections, and their safety in preexcited arrhythmias has not been demonstrated. METHODS AND RESULTS: We examined the effects of intravenous adenosine on accessory atrioventricular (AV) connections in 30 patients with the Wolff-Parkinson-White syndrome. Intravenous adenosine (12 mg, rapid bolus) was administered to 14 patients (group 1) during continuous atrial pacing at a cycle length 20 msec below that required to cause 2:1 conduction block in the accessory connection (mean pacing cycle length 261 +/ 41 msec). After adenosine, transient 1:1 conduction occurred via the accessory connection in 12 of 14 patients, indicating a shortening of antegrade refractoriness. In three of seven patients, this effect was abolished after intravenous propranolol (0.2 mg/kg). Nineteen patients (group 2) received adenosine (0.17 +/- 0.04 mg/kg) during induced, preexcited atrial arrhythmias. The minimum RR interval during preexcited atrial fibrillation transiently decreased (252 +/- 44 msec to 224 +/- 35 msec, p less than 0.01) after adenosine, but no change in average RR interval was observed (360 +/- 59 msec to 357 +/- 60 msec, NS). The preexcited ventricular response to atrial flutter was transiently accelerated in five of eight patients (415 +/- 21 msec to 360 +/- 49 msec, p less than 0.05) due to shortening of flutter cycle length (207 +/- 10 msec to 180 +/- 24 msec, p less than 0.05). However, 2:1 accessory connection conduction was maintained in all eight patients. All effects were short lived, with the decrease in RR interval during atrial fibrillation occurring for a maximum of two RR intervals only. No patient suffered ventricular arrhythmias or hemodynamic deterioration. CONCLUSIONS: Adenosine shortens antegrade refractoriness of accessory AV connections, and in some patients this action is mediated by beta adrenergic stimulation. Adenosine may cause acceleration of preexcited atrial arrhythmias, but these effects are transient and should not discourage the use of adenosine as a diagnostic agent in broad complex, regular tachycardias of uncertain origin. PMID- 1934372 TI - Psychological factors related to prehospital delay during acute myocardial infarction. AB - BACKGROUND: Prior studies have had difficulty identifying factors that significantly explain patients' delay in responding to symptoms of acute myocardial infarction (AMI). METHODS AND RESULTS: We therefore examined factors affecting the time between symptom onset and hospital arrival for 103 AMI patients admitted to a Detroit metropolitan hospital between October 1989 and January 1990. Variables evaluated included demographic and medical history factors, psychological characteristics of somatic and emotional awareness, and type A behavior. The mean prehospital delay time was 9.0 +/- 10.8 hours (median, 5.0 hours; range, 0.25-62.0 hours). Delay time was not significantly associated with demographic or medical history categories or with type A behavior. Of study variables that can be identified prior to evolution of an AMI, somatic and emotional awareness were the only factors significantly predictive of delay time. Patients who were more capable of identifying inner experiences of emotions and/or bodily sensations sought treatment significantly earlier than patients with low emotional or somatic awareness (low emotional awareness median delay, 12.8 hours; high emotional awareness median delay, 3.8 hours; low somatic awareness median delay, 7 hours; high somatic awareness median delay, 4 hours). CONCLUSIONS: Variations in sensitivity to bodily sensations and emotions appear to play an important role in treatment seeking and thus potentially in treatment outcome for AMI patients. Assessment of these characteristics in patients with coronary risk factors could allow early identification of persons at risk of excessive delay in responding to symptoms of AMI. PMID- 1934373 TI - Endothelial dysfunction of the coronary microvasculature is associated with coronary blood flow regulation in patients with early atherosclerosis. AB - BACKGROUND: The vascular endothelium is capable of regulating tissue perfusion by the release of endothelium-derived relaxing factor to modulate vasomotor tone of the resistance vasculature. METHODS AND RESULTS: To test whether atherosclerosis is associated with a functional abnormality of endothelium-mediated microvascular relaxation affecting coronary blood flow regulation, we compared coronary blood flow responses with cold pressor testing with the response of the coronary vasculature to acetylcholine (an endothelium-dependent vasodilator) and to papaverin (a direct dilator of vascular smooth muscle) in 12 normal control patients and in 19 patients with non-flow-limiting epicardial atherosclerosis (CAD). The drugs were subselectively infused into the left anterior descending coronary artery via a Doppler catheter, and the response in coronary blood flow was assessed by measuring intracoronary blood flow velocity and cross-sectional arterial area (quantitative angiography). Coronary vascular resistance decreased in all normal control patients by -24.1 +/- 5.5% (mean +/- SD) during the cold pressor test, whereas the CAD patients demonstrated a variable coronary vascular resistance response to cold pressor testing despite comparable changes in the rate-pressure product. The slopes of the acetylcholine dose-blood flow response (percent change in coronary blood flow/dosage of acetylcholine) were significantly reduced in the CAD patients with 38.5 +/- 24.8 compared with the normal patients (80.8 +/- 28.1; p less than 0.001). Although coronary blood flow responses to papaverin were slightly but significantly (p less than 0.05) reduced in the CAD patients, the response to the endothelium-dependent dilator acetylcholine was considerably out of proportion to the papaverin response in these patients compared with the normal patients. The capacity of the coronary system to increase blood flow in response to acetylcholine expressed as relative proportion of the maximal papaverin response was 52.5 +/- 18.2% in the normal control patients but only 33.6 +/- 23.6% in the CAD patients (p less than 0.025 versus normals). There was a significant negative correlation (r = -0.69; p less than 0.0001) between cold pressor test-induced changes in coronary vascular resistance and the capacity of the coronary system to increase blood flow in response to acetylcholine. CONCLUSIONS: Early stages of epicardial atherosclerosis are associated with an impairment in endothelium-dependent dilation of the coronary microvasculature, indicating that the pathophysiological consequences of atherosclerosis may extend into the human coronary microcirculation. The correlation between cold pressor test-induced coronary vascular resistance changes and the extent of endothelial dysfunction suggests a relation between endothelial function of the microvasculature and coronary blood flow regulation during sympathetic stimulation associated with increased myocardial work. PMID- 1934374 TI - Effects of calcitonin gene-related peptide on normal and atheromatous vessels and on resistance vessels in the coronary circulation in humans. AB - BACKGROUND: Calcitonin gene-related peptide (CGRP) is a potent dilator of normal epicardial coronary vessels in humans, but its effects on myocardial blood flow and atheromatous coronary vessel diameter are unknown. METHODS AND RESULTS: Seven patients were entered for study of the effects of CGRP on coronary blood flow and 13 for the comparison of its effects on normal and atheromatous coronary arteries. In the first seven patients, left anterior descending artery (LAD) diameter at an angiographically normal site, coronary sinus oxygen saturation (CSO2S), systemic blood pressure, and heart rate were measured during intracoronary infusion of increasing concentrations of CGRP (up to 200 ng/ml at 2 ml/min) followed by intracoronary adenosine (0.267 micrograms/ml at 2 ml/min) and finally intracoronary glyceryl trinitrate (GTN) (5 micrograms/ml at 2 ml/min). CGRP dilated the normal segment of the LAD by 22.6 +/- 8% (mean +/- 95% confidence interval), p less than 0.001, with only a small increase in CSO2S from 40.1 +/- 2.7% to 47.3 +/- 2.7%, p less than 0.001. Adenosine, a potent dilator of myocardial resistance vessels, caused no further increase in LAD diameter but caused a rise in CSO2S from 47.3 +/- 2.7% to 76.0 +/- 2.7%, p less than 0.001. GTN caused no further increase in LAD diameter. As heart rate-blood pressure product remained unchanged throughout the study, the increase of CSO2S indicated only a small increase in myocardial blood flow after CGRP infusion. In 13 patients with atheromatous coronary artery disease, the effects of intracoronary CGRP at angiographically normal sites, stenoses, angiographically normal sites immediately adjacent to stenoses, and sites of coronary artery wall irregularity were compared after intracoronary infusion of a single dose of CGRP (200 ng/ml at 2 ml/min) followed by intracoronary GTN (5 micrograms/ml at 2 ml/min). At these four sites, CGRP resulted in dilatation by 17.0 +/- 5.6%, 15.3 +/- 12.1% (NS), 7.6 +/- 5.4% (NS), and 15.9 +/- 7.8%, respectively. There was no significant further dilatation after GTN at any of the four sites. CONCLUSIONS: These data indicate that CGRP has little effect in humans at rest on coronary resistance vessels in nonischemic myocardium but causes marked dilatation of normal arteries and variable dilatation of atheromatous epicardial arteries. PMID- 1934375 TI - Correlates of sodium-lithium countertransport. Findings from the Gubbio Epidemiological Study. The Gubbio Collaborative Study Group. AB - BACKGROUND: Numerous reports have presented evidence for a positive association between the maximal velocity of the sodium-lithium countertransport (Na-Li CT) in erythrocytes and hypertension. The nature of this association remains to be clarified. METHODS AND RESULTS: This report presents correlates of Na-Li CT in a population sample of 3,591 people aged 5-74 years. Males had higher mean age specific levels of Na-Li CT than females except for the 5-14-year age stratum. In adults aged 25-74, for both men (n = 1,044) and women (n = 1,192), body mass index, plasma uric acid and glucose, alcohol consumption, and red blood cell mean corpuscular volume were positively related to countertransport in multivariate analyses; plasma high-density lipoprotein (HDL) cholesterol and plasma potassium were inversely related. Plasma non-HDL cholesterol was independently and directly related to Na-Li CT in women, and plasma sodium was inversely associated with Na Li CT in men. These relations prevailed for men when persons with hypertension were excluded from the analyses and prevailed in part for women. When stepwise regression analyses were done for all men and women combined (n = 2,236), sex ceased to be significantly related to countertransport with plasma uric acid and alcohol intake in the model. In adults of either sex, no independent association was detected between Na-Li CT and age, heart rate, or the ratios of sodium to potassium or of sodium to creatinine in overnight untimed urine. CONCLUSIONS: In both sexes, Na-Li CT is significantly and independently associated with a number of metabolic variables (plasma uric acid, plasma glucose, body mass index, plasma potassium, and life-style habits [e.g., alcohol intake]). Further research is needed to elucidate the meaning of the significant associations between Na-Li CT and the foregoing variables (all of them also related to blood pressure). PMID- 1934376 TI - Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project Investigators and Staff. AB - BACKGROUND: To determine whether there is an association between diet and plasma insulin concentration that is independent of obesity, we studied the relation of dietary composition and caloric intake to obesity and plasma insulin concentrations in 215 nondiabetic men aged 32-74 years with angiographically proven coronary artery disease. METHODS AND RESULTS: After adjusting for age, the intake of saturated fatty acids and cholesterol were positively correlated (p less than 0.05) with body mass index (r = 0.18, r = 0.16), waist-to-hip circumference ratio (r = 0.21, r = 0.22), and fasting insulin (r = 0.26, r = 0.23). Carbohydrate intake was negatively correlated with body mass index (r = 0.21), waist-to-hip ratio (r = -0.21), and fasting insulin (r = -0.16). Intake of monounsaturated fatty acids did not correlate significantly with body mass index or waist-to-hip circumference ratio but did correlate positively with fasting insulin (r = 0.24). Intake of dietary calories was negatively correlated with body mass index (r = -0.15). In multivariate analysis, intake of saturated fatty acids was significantly related to elevated fasting insulin concentration independently of body mass index. CONCLUSIONS: These cross-sectional findings in nondiabetic men with coronary artery disease suggest that increased consumption of saturated fatty acids is associated independently with higher fasting insulin concentrations. PMID- 1934377 TI - Growth of the great vessels in the normal human fetus and in the fetus with cardiac defects. AB - BACKGROUND: There is a paucity of quantitative anatomic data regarding human great vessel development that could be useful as a reference for fetal echocardiographers who must distinguish abnormal from normal cardiac development at early stages. METHODS AND RESULTS: To determine normal growth patterns, we plotted the diameters of the aortic and pulmonary valves, ductus arteriosus, aortic isthmus, and descending aorta in 274 autopsy specimens from nonselected spontaneous abortuses of normal karyotype. There was a linear increase in the diameters of these structures within the developmental period studied (10-26 weeks). A relative narrowing of the aorta at the isthmus compared with the aortic valve and descending aorta probably indicates that the majority of fetal left heart output goes to the developing heart and brain. In contrast to previous studies of late gestation and neonatal animals, however, we found that the diameter of the aortic isthmus was larger than that of the ductus arteriosus, suggesting substantial isthmic blood flow in these midtrimester fetuses. Among nineteen other hearts with diverse defects, both of two hearts with a narrow isthmus had an enlarged ductus arteriosus and one heart with pulmonary atresia/intact septum had a narrow ductus and increased aortic valve diameter. CONCLUSIONS: During midgestation, the normal heart may have substantial aortic isthmic blood flow that diminishes due to rerouting in late gestation when increased requirements of the fetal brain and other organs prevail. Although fetal shunts may explain some vessel abnormalities, the majority of cardiac defects in this study were not associated with abnormal growth of the great vessels within this developmental age range. PMID- 1934378 TI - Skeletal muscle metaboreceptor exercise responses are attenuated in heart failure. AB - BACKGROUND: Resting sympathetic nervous system activity is increased in heart failure. Whether sympathetic nervous system responses during exercise are increased is controversial. Furthermore, the role of muscle metaboreceptors and central command in regulating sympathetic outflow has been largely unexplored. METHODS AND RESULTS: Muscle sympathetic nerve activity (MSNA, peroneal nerve) was measured in nine heart failure subjects and eight age-matched control subjects during static exercise (30% maximal voluntary contraction) for 2 minutes and during a period of posthandgrip regional circulatory arrest. This maneuver isolates the metaboreceptor contribution to sympathetic nervous system responses. MSNA responses were similar during static exercise in the two groups. During posthandgrip regional circulatory arrest we observed a marked attenuation in MSNA responses in the heart failure subjects (15% increase in heart failure versus 57% increase in control subjects). A cold pressor test demonstrated a normal MSNA response to a potent nonspecific stimulus in the heart failure subjects (heart failure subjects, 141% increase; control subjects, 215% increase; NS). Nuclear magnetic resonance spectroscopy studies in five separate heart failure subjects and five control subjects suggested that the attenuated metaboreceptor response in heart failure was not due to reduced H+ production. CONCLUSIONS: Skeletal muscle metaboreceptor responses are impaired in heart failure. Because MSNA responses during static exercise are similar in the two groups, mechanisms aside from metaboreceptor stimulation must be important in increasing sympathetic nervous system activity. PMID- 1934379 TI - Randomized study to evaluate the relation between oral isosorbide dinitrate dosing interval and the development of early tolerance to its effect on left ventricular filling pressure in patients with chronic heart failure. AB - BACKGROUND: Early development of nitrate tolerance has been shown in patients with chronic congestive heart failure (CHF) receiving continuous nitroglycerin therapy. The influence of dosing interval of oral isosorbide dinitrate (ISDN), the nitrate preparation most widely used for the treatment of CHF, has not been investigated. METHODS AND RESULTS: We performed a prospective, randomized study to evaluate the effect of various regimens of oral ISDN on the development of early tolerance to its effect on left ventricular filling pressure in patients with moderate to severe CHF. Forty-four responders (20% or greater reduction in mean pulmonary artery wedge pressure lasting 1 hour or longer) were divided into four groups of 11 patients each, and randomized to receive their effective ISDN dose (40-120 mg) Q 4 hours, Q 6 hours, Q 8 hours, or t.i.d. (drug given at 0, 6, 12, and 24 hours allowing 12 hours of ISDN washout interval between the third and fourth doses). All groups demonstrated a significant and comparable reduction in LV filling pressure following administration of the first ISDN dose. Early attenuation of hemodynamic response was demonstrated with frequent dosing (Q 4 hours and Q 6 hours) ISDN. Tolerance was with a Q 8-hour regimen as demonstrated by preserved hemodynamic response to each dose. The effect of each dose, however, was short-term, with return of pulmonary artery wedge pressure to baseline level at 2 to 4 hours, resulting in an intermittent effect totaling no longer than 12 hours of the 30-hour study period. The use of a t.i.d. regimen resulted in marked attenuation of response after the third dose with complete restoration of nitrate effect following a 12-hour washout period between the third and fourth doses. ISDN plasma concentration was measured in five patients in each of the Q 4- and Q 8-hour groups. In the Q 4-hour group, plasma levels were significantly higher after administration of the last dose than after the first dose (area under the curve, 242 +/- 216 versus 123 +/- 130 ng/ml, p less than 0.05), and trough levels before administration of the second and the fifth dose (15 +/- 17 and 27 +/- 27 ng/ml, respectively) were both markedly higher than the baseline value of 2 +/- 4 ng/ml. CONCLUSIONS: Our data demonstrate the development of tolerance and early attenuation of effect on left ventricular filling pressure with frequent oral dosing (Q 4 and Q 6 hours) with ISDN in patients with chronic CHF, which may be related to persistently elevated trough blood levels of ISDN. The development of tolerance can be reversed after a washout period of 12 hours and can be prevented with a Q 8-hour administration. These regimens, however, are limited by an inconsistent effect. Although long-term implications of these findings need further evaluation, the present study demonstrates the difficulty of maintaining a persistent ISDN-mediated reduction in left ventricular filling pressure in patients with chronic, moderate to severe CHF. These results suggest the need to use intermittent ISDN therapy allowing a daily nitrate washout interval and the rationale for combined vasodilator therapy in patients with CHF. PMID- 1934380 TI - Short-term vasodilator effect of captopril in patients with severe mitral regurgitation is parasympathetically mediated. AB - BACKGROUND: Few data exist regarding the effects of angiotensin converting enzyme inhibitors in patients with regurgitant valvular lesions. We postulated an immediate improvement in cardiac performance with captopril in mitral regurgitation, which, in a hemodynamically compensated group of patients, might be mediated through parasympathetic vasodilation rather than through blockade of angiotension converting enzyme. METHODS AND RESULTS: Hemodynamics were examined before and 90 minutes after oral captopril (25-50 mg) in 18 patients (mean age, 31 years) with chronic, severe mitral regurgitation in New York Heart Association functional class II and III. One group of patients was given captopril alone (group 1, n = 9) and a second group was given captopril plus atropine 0.04 mg/kg i.v. (group 2, n = 9). Captopril alone (group 1) produced decreases in heart rate (90-81 beats/min, p less than 0.001), mean arterial pressure (90-73 mm Hg, p less than 0.001), systemic resistance (28-23 Wood units, p = 0.068), and pulmonary wedge pressure (19-14 mm Hg, p less than 0.001). There was no improvement in either arteriovenous oxygen difference or thermodilution cardiac output; in fact, the latter slightly declined (3.45-3.35 l/min, p = 0.002). Pretreatment with atropine (group 2) diminished the effects of captopril on heart rate (107-103 beats/min, p = 0.065 for atropine effect by two-way ANOVA), mean arterial pressure (88-82 mm Hg, p = 0.01 for atropine effect), and systemic resistance (26 27 Wood units, p = 0.04 for atropine effect). CONCLUSIONS: In patients with chronic, severe mitral regurgitation, captopril reduced systemic arterial and left ventricular filling pressures but did not immediately augment cardiac output as expected. Furthermore, the modest systemic vasodilator effect of captopril was parasympathetically mediated. PMID- 1934381 TI - Evaluation of thromboxane production and complement activation during myocardial ischemia in patients with angina pectoris. AB - BACKGROUND: The complement system and arachidonic acid metabolites are involved in severe myocardial ischemia such as myocardial infarction. Furthermore, there is experimental evidence for C5a participation in thromboxane production. METHODS AND RESULTS: We examined whether C5a and thromboxane are produced during brief and reversible episodes of myocardial ischemia induced in patients with stable angina. Twenty-five patients underwent either atrial pacing or percutaneous transluminal coronary angioplasty associated with arterial and coronary sinus blood sampling. Rapid atrial stimulation of patients with effort angina caused significant ST segment depression (delta ST = -1.7 +/- 0.2 mm), decreased fractional lactate extraction (from +12.8 +/- 2.5% baseline to -13.7 +/- 4.6% at peak ischemia, n = 13, p less than 0.001), and increased coronary sinus plasma thromboxane B2 levels (from 345 +/- 85 pg/ml baseline to 1,684 +/- 64 pg/ml at peak ischemia, p less than 0.01). Changes of fractional lactate extraction correlated significantly with changes of coronary sinus plasma levels of thromboxane B2. There was no change of coronary sinus 6-keto-PGF1 alpha levels. Similar pacing of control subjects (n = 6) did not cause release of lactate or thromboxane. Seventeen other patients underwent exercise testing with noninvasive measurements of thromboxane and prostacyclin metabolites in urinary samples collected before and after the test. No detectable increase of urinary 11 dehydrothromboxane B2 was measured in patients with stable angina after exercise induced myocardial ischemia. However, basal 11-dehydrothromboxane B2 levels were significantly higher in patients with angina (105 +/- 25 pg/mmol creatinine, n = 9) than in control patients (45 +/- 8 pg/mmol creatinine, n = 8, p less than 0.05 between groups). Coronary sinus plasma levels of the anaphylatoxin C5a always remained below 4 ng/ml in patients undergoing pacing. More severe myocardial ischemia after coronary angioplasty (percent lactate extraction decreased from +24.8 +/- 2.7% baseline to -41.6 +/- 22.4% at peak ischemia, p less than 0.05) was not associated with C3a or C5b-9 generation. In all patients, there was neither platelet sequestration nor platelet alpha-granule release (no changes of beta-thromboglobulin/platelet factor 4 levels) into the coronary sinus plasma. CONCLUSIONS: Patients with stable angina have chronically increased thromboxane synthesis as assessed by excretion of urinary metabolites. Thromboxane is acutely released into the coronary sinus during pacing-induced ischemia without significant intracoronary platelet aggregation. Complement does not appear to be activated in stable angina during brief and reversible episodes of myocardial ischemia and does not contribute to thromboxane production. PMID- 1934382 TI - Hemostatic effects of tranexamic acid and desmopressin during cardiac surgery. AB - BACKGROUND: Desmopressin-induced release of tissue plasminogen activator from endothelial cells may explain the absence of its hemostatic effect in patients undergoing cardiac surgery. Prior administration of the antifibrinolytic drug tranexamic acid might unmask such an effect, and combination therapy might thereby improve postoperative hemostasis. METHODS AND RESULTS: A double-blinded design randomly allocated 163 adult patients undergoing coronary revascularization, valve replacement, both procedures, or repair of atrial septal defect to four treatment groups: placebo, tranexamic acid given as 10 mg/kg over 30 minutes followed by 1 mg.kg-1.hr-1 for 12 hours initiated before skin incision, desmopressin given as 0.3 micrograms/kg over 20 minutes after protamine infusion, and both drugs. One surgeon performed all operations. Blood loss consisted of mediastinal tube drainage over 12 hours. Follow-up visits sought evidence of myocardial infarction and stroke. Desmopressin decreased neither the 12-hour blood loss nor the amount of homologous red cells transfused. Tranexamic acid alone significantly reduced 12-hour blood loss, by 30% (mean, 318 versus 453 ml; p less than 0.0001), without enhancement by desmopressin. Tranexamic acid also decreased the proportion of patients receiving homologous blood within 12 hours of operation (8% versus 21%, p = 0.024) and within 5 days of operation (22% versus 41%, p = 0.011). CONCLUSIONS: Desmopressin exerts no hemostatic effect, with or without prior administration of antifibrinolytic drug. Prophylactic tranexamic acid alone appears economical and safe in decreasing blood loss and transfusion requirement after cardiac surgery. PMID- 1934383 TI - Role of collagen in acute myocardial infarct expansion. AB - BACKGROUND: We sought to determine if damage to the myocardial collagen network was the cause of infarct expansion. METHODS AND RESULTS: Using polarized light microscopy, we examined sections from rat hearts obtained at 1, 2, 3, and 4 days after permanent coronary artery occlusion. Three features of the collagen network likely to be important in resisting infarct expansion were assessed: collagen quality, collagen quantity, and collagen organization. We observed a decrease in the number of normally birefringent collagen fibers in the infarct as early as 1 day after infarction. This decrease correlated significantly with time (r = 0.989, p less than 0.001). In addition, we found that the fewer normally birefringent collagen fibers present, the greater the degree of infarct expansion (assessed by measurement of total left ventricular cross-sectional area). At 4 days after infarction, we noted a loss of intermyocyte collagen struts and loss of interstitial space. These changes coincided with the onset of pronounced infarct expansion. The loss of collagen struts is consistent with the concept that expansion proceeds via slippage of myocytes previously tethered by the struts. The loss of interstitial space may represent the resolution of interstitial edema, which could further weaken the ventricular wall. CONCLUSIONS: The correlation of infarct expansion with collagen damage and the loss of support provided by collagen struts suggest that collagen is important in maintaining structural integrity after acute myocardial infarction. PMID- 1934384 TI - Psychosocial factors impair vascular responses of coronary arteries. AB - BACKGROUND: Four sets of monkeys were used to examine the effect of chronic psychosocial disruption and diet on dilator responses of coronary arteries. METHODS AND RESULTS: One set consisted of monkeys consuming monkey chow and living in a stable social setting (nonatherosclerotic controls, n = 6). Three sets consumed an atherogenic diet for 14 months followed by one of three treatments for the next 16 months: 1) a high-cholesterol diet and housed in unstable social groups (n = 9); 2) a low-cholesterol diet and housed in unstable (n = 8); or 3) stable groups (n = 10). Quantitative coronary angiography revealed that intracoronary infusion of acetylcholine resulted in a change of diameter (versus infusion of 5% dextrose in water) of +4 +/- 1% in control monkeys and -11 +/- 4% in unstable monkeys consuming a high-cholesterol diet (p less than 0.05). In monkeys consuming the cholesterol-lowering diet, the change in artery diameter was +2 +/- 4% in stable and -10 +/- 4% in unstable social conditions (p less than 0.05) despite a similar plaque size (0.4 +/- 0.2 and 0.5 +/- 0.1 mm2) and total plasma cholesterol concentrations (179 +/- 9 and 172 +/- 6 mg/dl), respectively. The arterial response to nitroglycerin was similar among all groups of monkeys. CONCLUSIONS: We conclude that chronic social disruption is associated with relative arterial constriction in response to acetylcholine in atherosclerotic monkeys consuming a cholesterol-lowering diet. PMID- 1934385 TI - Mechanism of ischemic mitral regurgitation. An experimental evaluation. AB - BACKGROUND: Papillary muscle dysfunction (PMD) has been implicated in the pathogenesis of ischemic mitral regurgitation (MR). We hypothesized that ischemic MR is not caused by PMD and/or dysfunction of the myocardial regions from where the papillary muscles arise but is related to reduction in global left ventricular (LV) function. To test this hypothesis, three groups of dogs were studied. METHODS AND RESULTS: In group 1 dogs (n = 8), varying degrees of regional and global LV dysfunction were produced. In group 2 dogs (n = 7), the circulation to the papillary muscles was isolated from that of the rest of the LV. Dysfunction of one or both papillary muscles was produced without producing global LV dysfunction. Global LV dysfunction was also produced while keeping papillary muscle function intact. The degree of MR (assessed using contrast echocardiography) was correlated in both groups of dogs with thickening of the papillary muscles and regional and global LV function. In the group 3 dogs (n = 6), the spatial distribution of blood flow within each papillary muscle was determined during ischemia by using radiolabeled microspheres. Thickening of the papillary muscles was assessed at three different levels along their lengths and was correlated with average blood flow at these levels. In group 1 dogs, MR was noted only when global LV function was affected and its severity correlated inversely with global LV function (r = -0.84 with peak positive LV dP/dt and r = 0.95 with global LV thickening, respectively). In comparison, there was poor correlation between MR and anterior and posterior papillary muscle thickening (r = -0.38 and r = -0.49, respectively). In group 2 dogs, MR did not occur in the presence of either PMD or akinesia of the immediately adjacent LV myocardium. MR occurred only when global LV dysfunction was produced (with the papillary muscle function intact), and its severity correlated inversely with global LV function (r = -0.92 with LV dP/dt and r = -0.86 with global LV thickening, respectively). There was poor correlation between the degree of MR and thickening of the anterior and posterior papillary muscles (r = -0.24 and r = -0.38, respectively). In both groups of dogs, MR was associated with incomplete mitral leaflet closure (IMLC), and the severity of MR correlated linearly with the degree of IMLC (r = 0.98). MR was never associated with mitral valve prolapse. In the group 3 dogs, despite more inhomogeneous flow during ischemia to the anterior compared with the posterior papillary muscle, mean thickening of these muscles was similar (3 +/- 10% and 3 +/- 4%, respectively). Furthermore, there was minimal variability in thickening between different parts of the muscles (3 +/- 2% and 5 +/- 3%, respectively). CONCLUSIONS: It is concluded that PMD and/or dysfunction of the immediately adjacent LV myocardium does not result in MR. MR occurs during ischemia only when global LV function is affected, even when thickening of the papillary muscles and the immediately adjacent LV remains intact. MR in this situation is related to IMLC; the greater the degree of IMLC, the greater the MR. These findings suggest that the mechanism of ischemic MR is not related to PMD. There may also be important therapeutic implications of these findings. PMID- 1934386 TI - High-energy His bundle ablation. A treatment of last resort. PMID- 1934387 TI - Intravascular ultrasound. A fantastic voyage. PMID- 1934388 TI - Understanding delay in response to symptoms of acute myocardial infarction. A compelling agenda. PMID- 1934389 TI - Cardiopulmonary interactions during CPR. PMID- 1934390 TI - A new mechanism linking stress to coronary pathophysiology? PMID- 1934391 TI - Prognostic value of 201Tl myocardial scintigraphy. PMID- 1934392 TI - Fibrinolytic activity and response to t-PA in blacks and whites. PMID- 1934393 TI - Third World profile of racial differences in thrombolytic effects of streptokinase. PMID- 1934394 TI - ATP derangement versus free radical-mediated injury. PMID- 1934395 TI - ACC/AHA guidelines for cardiac catheterization and cardiac catheterization laboratories. American College of Cardiology/American Heart Association Ad Hoc Task Force on Cardiac Catheterization. AB - It is evident that the practice of cardiac catheterization has undergone, and continues to undergo, marked change. Most prominent are the recent very rapid proliferation of catheterization laboratories in general and the development of newer types of catheterization laboratory. No uniform definitions exist for these newer laboratories, so meaningful communication is difficult. The new settings are of particular concern because their location, mobility, organization, and ownership raise questions about the quality of patient care. Most difficult to address are the questions about patient safety and physician conflict of interest. There are no objective data in peer-reviewed literature to support the reported safety and cost savings of these newer settings. Through deliberations, surveys, interviews, and correspondence with the cardiology community embraced by the ACC and the AHA, the task force generally found that in freestanding catheterization laboratories, access to emergency hospitalization may be delayed, and appropriate oversight may be lacking. Additionally, opportunities for self referral may be fostered and the perception of commercialism and entrepreneurial excess in practice created. All of these problems must be avoided. The growth and development of some freestanding facilities, particularly the mobile laboratories, do not seem to have been driven by an increased need in remote communities or for temporary support but rather almost exclusively by a desire to capture market share. Accordingly, a series of definitions, guidelines, and recommendations for the laboratories as well as for patient selection has been developed. The consensus was that a very restrictive and cautious attitude to the newer settings is appropriate at this time. The justification for development or expansion of cardiac catheterization services must be patient need. Documentation of this need must be based on objective estimates of the number of patients with known or suspected cardiac disease who meet generally accepted indications for laboratory study. Concerns about the lack of data from prospective clinical trials of patient safety in such a group necessitate a very cautious attitude toward any new catheterization services, in particular those without in-house cardiac surgical support. In view of the lack of appropriately controlled safety and need data for hospital-based, mobile, or freestanding laboratories operating without on-site (accessible by gurney) cardiac surgery facilities, the task force reaffirms the position that further development of these services cannot be endorsed at this time. In addition, there is reason for major concern that such proliferation in catheterization services may contribute to increasing costs and troubling ethical questions. PMID- 1934396 TI - Guidelines for pediatric therapeutic cardiac catheterization. A statement for health professionals from the Committee on Congenital Cardiac Defects of the Council on Cardiovascular Disease in the Young, the American Heart Association. PMID- 1934397 TI - Thoracic aortic surgery. AB - Between 1982 and 1989, 119 patients had repair of thoracic aortic pathology. Thirty-seven had repair of ascending aortic aneurysms, with an 11% hospital mortality. Forty-one patients had urgent repair of acute type A aortic dissections, with a 32% hospital mortality. The independent predictors of mortality were the use of crystalloid cardioplegia, aortic dissection, and the use of an intraluminal prosthesis or the inclusion surgical technique. Better grafts and the resection technique has reduced mortality since 1986. Seventeen patients had their primary pathology in the aortic arch, with a 47% hospital mortality. The urgency of the procedure and crystalloid cardioplegia predicted an unsuccessful outcome. Seventeen patients had descending aortic aneurysms repaired, with an 18% mortality. The urgency of surgery was the predictor of mortality. Seven patients had a descending thoracic aortic disruption repaired, with one death (14%). Better graft materials, surgical techniques, and methods of myocardial protection have contributed to the improved results of thoracic aortic surgery in recent years. PMID- 1934398 TI - Influence of time from donor death to graft harvest on conduit function of cryopreserved aortic allografts in lambs. AB - We examined the influence of time from donor death to graft harvest on conduit function of aortic allografts in the thoracic aortic position in 18 lambs (mean weight, 11.4 kg). Five grafts were harvested immediately after donor death (fresh), seven at 24 hours, and six at 48 hours following cadaver storage at 4 degrees C. All grafts were treated with antibiotics and were stored by cryopreservation. All animals were catheterized postoperatively and at 3, 6, 9, and 12 months. One animal in the 24-hour group developed an allograft aneurysm, and another one died from a ruptured allograft; one graft in the fresh group occluded by nine months. No animal, however, in the 48-hour group either developed an aneurysm or occluded. There was in fact minimal change in graft diameter over time (p greater than 0.05), while the native aorta grew appropriately (greater than 50%, p less than 0.01). Forty-eight hour delay from donor death to graft harvest did not have significant effect on conduit function. This information may expand the donor pool for allografts. PMID- 1934399 TI - Mitral valve replacement in dilated canine hearts with chronic mitral regurgitation. Importance of the mitral subvalvular apparatus. AB - The importance of the mitral subvalvular apparatus in terms of left ventricular (LV) mechanics and energetic efficiency in the chronically dilated canine heart was assessed in nine dogs with surgically induced mitral regurgitation. Miniature radiopaque tantalum markers were implanted into the myocardium to measure LV volume. Biplane cinefluoroscopic images obtained 1 week and 3 months after creation of mitral regurgitation confirmed the presence of LV dilatation. Mitral valve replacement with preservation of all chordae tendineae was then performed. LV systolic function and derived energetics were then assessed during transient caval occlusion both before and after chordal division by using exteriorized snares. Global LV systolic mechanics, as assessed by the slopes of the end systolic pressure volume (Ees) and end-systolic stress volume (Ms) relations, fell by 46% (11.7 +/- 2.8 versus 6.3 +/- 1.4 mm Hg/ml, p less than 0.001) and 33% (17.8 +/- 4.0 versus 12.0 +/- 5.1 kdyne/cm5, p = 0.0001), respectively, when the chordae were divided. Chordal severing also increased systolic LV wall stress or LV afterload. In terms of calculated myocardial energetics, the slopes of the stroke work-end-diastolic volume and pressure volume area-end-diastolic volume relations declined significantly by 20% (85 +/- 14 versus 68 +/- 16 mm Hg) and 11% (116 +/- 20 versus 104 +/- 20 mm Hg) after cutting the chordae, thereby indicating reduced external stroke work and mechanical energy generated at any given level of preload. Moreover, the efficiency of energy transfer from pressure volume area to external stroke work fell by 19% (p less than 0.001). Since effective systemic arterial elastance (Ea) did not change, the Ea/Ees ratio (index of ventriculoarterial [V-A] coupling) increased from 0.93 +/- 0.27 to 1.67 +/- 0.62 (p = 0.006). Therefore, chordal division in dilated dog hearts due to chronic mitral regurgitation resulted not only in deterioration of systolic LV mechanics but also deleterious changes in calculated LV energetics and efficiency due to exacerbated mismatch in V-A coupling between the left ventricle and the systemic arterial bed, unfavorable loading conditions, and exhaustion of preload reserve. These observations in the low-pressure, volume-overloaded heart due to chronic mitral regurgitation underscore the importance of the mitral subvalvular apparatus for optimal LV systolic performance and energetic efficiency. PMID- 1934401 TI - Natural history of left ventricular performance at rest and during exercise after aortic valve replacement for aortic regurgitation. AB - Previous studies of left ventricular performance in aortic regurgitation uniformly indicate improvement within the year after aortic valve replacement but differ regarding the likelihood of additional later improvement. To resolve this difference, to more precisely define the pattern of postoperative left ventricular performance variation, and to assess the impact of valve replacement on ejection fraction during exercise, we evaluated radionuclide cineangiograms obtained annually or nearly annually for approximately 5 years in 21 prospectively studied patients who had undergone valve replacement for aortic regurgitation. Ejection fraction rose from less than 8 months before operation to 5-11 (average 7) months after operation and continued to rise for 1 additional year (rest) and 2 additional years (exercise) before reaching a stable plateau until the final study 54-72 (average 63) months postoperatively. Mean ejection fractions at rest were 45% preoperatively, 50% less than 1 year postoperatively (p = 0.12), 54% at year 1-2 (p = 0.01 versus less than 1 year), 56% at year 2-3 (NS versus year 1-2) and year 4-6 (NS versus year 1-2 or 2-3), and during exercise were 39% preoperatively, 49% less than 1 year postoperatively (p less than 0.01), 54% at year 1-2 (p less than 0.01 versus less than 1 year, NS versus year 2-3, p less than 0.05 versus year 4-6), 60% at year 2-3, and 61% at year 4-6 (NS versus year 2-3). Late improvement was found most consistently among patients with relatively depressed performance before operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934400 TI - Valve repair in rheumatic mitral disease. AB - Emerging evidence indicates that etiology plays an essential role in the results of mitral valve repair. In an attempt to evaluate the possibilities and problems of repair in a rheumatic population, all consecutive patients treated between July 1988 and July 1990 were reviewed. Three hundred and four patients at risk of undergoing a repair were studied. The mean age was 31.3 years. In 78 patients (25.6%) the valve was considered beyond repair and immediately replaced (MVR). In 26 patients (8.5%) an unsuccessful attempt at repair was followed by replacement (attempts), and 200 (65.7%) underwent a successful repair (repair). The repair group was younger (p less than 0.001) and had less tricuspid involvement (p less than 0.005). The repair rate was highest in regurgitant lesions (79.4% repaired, p less than 0.005). The attempts group was very similar to the MVR group. The total hospital mortality was 3.2%. For MVR it was 3.8%, for attempts 19.2%, and for repairs 1.0%. The incidence of embolism was 3.34%/patient/yr for the mechanical, 3.06%/patient/yr for bioprosthesis, and 2.19%/patient/yr for repairs. Only 7.5% of repairs were anticoagulated. A reoperation was needed in 26 patients: one for bioprosthesis, one for aortic repair failure, and 24 for mitral repair dysfunction (12.1% of all surviving repairs). The reoperation incidence after repair was 26.8% in patients with an age under 20 years and 4.5% in those over 20. Eight patients had active carditis and 10 severe hemolysis. There were eight late deaths (six prosthesis and two repairs), with an actuarial total survival at 30 months of 72.46 +/- 8.45% for prosthesis and 94.41 +/- 3.74% for repairs (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934402 TI - Emergency surgical intervention of acute aortic dissection with the rapid diagnosis by transesophageal echocardiography. AB - Forty-five serial patients with acute aortic dissection were examined by transesophageal color Doppler echocardiography (TEE), and the diagnosis was made without aortography. No complications related to TEE occurred. Sufficient information for surgery was immediately obtained at the bedside by the TEE examination. Forty-four of 45 patients (98%) were diagnosed accurately, and 20 emergency operations for patients with type A aortic dissection and six emergency operations for patients with type B aortic dissection were performed. In only one patient, a small intimal flap in the ascending aorta was not detected by TEE. The operative mortality rate was 20% and 50% for types A and B aortic dissections, respectively. As a result of the progress of biplanar TEE technology, an easier and more accurate diagnosis of patients with acute aortic dissection can be achieved. The immediate and accurate diagnosis of acute aortic dissection can be achieved by TEE at the bedside, and treatment strategy can be more precisely determined. PMID- 1934403 TI - Serial follow-up of an experimental bovine pericardial aortic bioprosthesis. Usefulness of pulsed Doppler echocardiography. AB - Echocardiography was used in the serial evaluation of 50 patients at 1, 3, and 7 years after aortic valve replacement with a new bovine pericardial aortic bioprosthesis. For valve sizes of 19-27 mm, at 7 years of follow-up mean transvalvular gradients (xGrad) ranged from 15.2 to 8.0 mm Hg, and calculated mean valve areas (AVA) ranged from 1.06 to 1.79 cm2. Acceptable xGrad and AVA were directly related to valve size and did not change in 48 asymptomatic patients. One patient at 7 years had marked calcific stenosis and degeneration requiring explanation. Echocardiography is useful in the long-term evaluation of bioprosthetic function, yielding information equivalent to cardiac catheterization data. This bovine pericardial valve offers good clinical and hemodynamic results at 7 years and is a suitable alternative when a bioprosthesis is indicated. PMID- 1934404 TI - Carpentier-Edwards porcine bioprostheses. Comparison of standard and supra annular prostheses at 7 years. AB - The performance of the Carpentier-Edwards supra-annular (CE-SAV) porcine bioprosthesis is compared with the Carpentier-Edwards standard (CE-S) porcine bioprosthesis at 7 years. The standard prosthesis was implanted in 1,195 patients between 1975 and 1987, while the supra-annular prosthesis was implanted in 1,956 patients between 1982 and 1989. The total follow-up for the standard prosthesis was 8,850 patient-years with a mean follow-up of 7.4 years, while for the supra annular prosthesis it was 7,317 years with a mean of 3.7 years. The follow-up for the standard prosthesis was 96.7% and for the supra-annular prosthesis was 97.6%. The freedom from structural valve deterioration (SVD) for aortic replacements is 96.1 +/- 0.9% for CE-S and 97.6 +/- 1.4% for CE-SAV at 7 years (p = NS). The freedom for mitral replacements from SVD is 89.1 +/- 1.7% and 88.6 +/- 2.8%, respectively, for CE-S and CE-SAV (p = NS). The freedom for multiple replacements at 7 years was 80.0 +/- 4.5% for CE-S and 97.8 +/- 1.5% for CE-SAV (p less than or equal to 0.05). The freedom from SVD for the age group equal to or less than 35 years is 79.0 +/- 4.7% for CE-S and 85.0 +/- 9.4% for CE-SAV (p = NS). The freedom for the age group 36-50 years is 85.2 +/- 2.8% and 90.4 +/- 4.5%, respectively, at seven years for the CE-S and CE-SAV prostheses (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934405 TI - Doppler color flow mapping assessment of residual shunt after closure of large ventricular septal defects. AB - Of 179 consecutive patients who underwent closure of a large ventricular septal defect (VSD) as part of reparative surgery under 2 years of age, 19 died early and 160 had echocardiographic evaluation that included Doppler color flow mapping at 8 +/- 7 days after repair. Sixty-one (38%) of patients had evidence of residual shunting in the peripatch area. Two independent observers measured the Doppler color jet width at the left septal surface; jet width was correlated with subsequent reoperation for residual VSD. Patients were divided into two groups by jet width measurement: group 1 measured 4 mm or greater (n = 4), and group 2 measured less than 4 mm (n = 57). Of the group 1 patients, three returned to the operating room for a large residual defect; one patient died without reoperation but was confirmed to have had a large defect by angiography. Four patients in group 2 underwent surgery for a residual VSD; two underwent reoperation for reasons other than a residual VSD and had closure of a small residual VSD; one patient thought to have a large residual VSD at reoperation was noted to have multiple muscular VSD and only a small residual VSD; and one patient had a small defect initially but returned 2 years later with late patch dehiscence. Sixty five percent of 23 group 2 patients reevaluated at a mean of 10 +/- 8 months after initial study no longer showed evidence of residual shunting. Residual Doppler color jets are frequently noted after repair of a large VSD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934406 TI - Arrhythmias after the Fontan procedure. Comparison of total cavopulmonary connection and atriopulmonary connection. AB - Arrhythmia was compared between 40 consecutive patients (pts) undergoing atriopulmonary connection (APC) and 40 undergoing total cavopulmonary connection (TCPC), between 1986 and 1990. Patients were not randomized, and those undergoing APC predominantly had tricuspid atresia (57.5% versus 15%) compared with pts undergoing TCPC who had more varied and complex cardiac defects. Before surgery there was no significant arrhythmia in either group. Hospital mortality was 15/40 and 6/40 for APC and TCPC, respectively (p less than 0.05). Early after APC nine pts developed atrial flutter (AFL) and eight died, while after TCPC only two developed AFL, and neither died (p less than 0.01). Fatal junctional ectopic tachycardia occurred in one pt in each group. During follow-up (38 +/- 8.5 months after APC versus 20 +/- 10 months after TCPC), new arrhythmia was uncommon (two AFL after APC with one death versus two AFL and one supraventricular tachycardia after TCPC with no deaths). Ambulatory ECG during follow-up showed arrhythmia in two APC and six TCPC pts (p = NS). The incidence of early arrhythmia and mortality associated with early arrhythmia appears to be less after TCPC compared with APC. PMID- 1934407 TI - Extracorporeal life support for cardiac assist in pediatric patients. Review of ELSO Registry data. AB - The collected data on extracorporeal membrane oxygenation (ECMO), now referred to as extracorporeal life support (ECLS), for pediatric cardiac support has not been analyzed. The purpose of this study was to review the Extracorporeal Life Support (ELSO) Registry data to evaluate the results, identify possible predictors of outcome, and attempt to establish criteria. From 1981 to June of 1990, 189 patients were placed on ECLS for cardiac assist. The age range was 0-204 months (median, 7 months). Mean time on ECLS was 115 +/- 75 hours. Fourteen patients were placed on ECLS as a bridge to transplant or for management of transplant rejection. All of the remaining 175 patients were treated in the postoperative period. The causes of mortality included lack of improvement in cardiovascular function in 69 (37%) of the patients, major central nervous system damage in 28 (15%), uncontrollable hemorrhage in three (2%), sepsis in three (2%), and pulmonary interstitial disease in two (1%). The Registry data were examined for predictors of outcome. There was no significant difference between survivors and nonsurvivors when compared for duration of ECLS, mechanical complications, arterial or venous blood gases, ventilation settings, or hemodynamics. Forty three percent of 189 pediatric patients treated with ECLS for cardiac failure survived. The highest survival, 61%, occurred in right-sided lesions and the lowest, 18%, in post-Fontan. Mediastinal bleeding, cardiac arrest, renal failure, and prolonged intubation were all associated with a poor outcome. Most deaths were attributed to irreversible cardiac or brain injury, suggesting that results could be improved by earlier identification of high-risk patients and earlier institution of ECLS. PMID- 1934408 TI - Risk factors for arrhythmia and death after Mustard operation for simple transposition of the great arteries. AB - From 1965 to 1980, 249 consecutive patients underwent a Mustard procedure for simple transposition of the great arteries. Hospital mortality was 23 of 249 (9.2%); follow-up for 24 years (mean, 11.7 +/- 6.1 yr) revealed 50 of 249 (20%) late deaths, of which seven were noncardiac, six were in the hospital, and 37 were sudden (27 patients with poor hemodynamics and 10 unexplained). Actuarial survival after 1, 10, and 20 years was 85, 75, and 67%. The instantaneous risk of death decreased rapidly after surgery but showed a second peak from 8 to 15 years postoperation. When last seen 87% were in New York Heart Association (NYHA) class I; 69% had sinus rhythm, 20% nodal rhythm, 10% atrial flutter, and 1% paced. Survival in uninterrupted sinus rhythm after 5, 10, and 20 years was 75, 62, and 47%. Nodal rhythm detected by annual ECG occurred in 69 patients. Excluding the early experience, the risk of loss of sinus rhythm was constant in time and constant throughout the experience (2.4%/yr). Atrial flutter was observed in 36 patients. Occurrence of atrial flutter was limited to two discrete surgical periods: the first operations (26 with atrial flutter of the first 50) and an ill defined period in the middle of the experience. Patients not operated on during these two periods were very unlikely to develop atrial flutter (one of 104, p less than 0.001). As for death, the hazard function showed a bimodal curve, the second peak appearing earlier from 5 to 11 years. If nodal rhythm was noted on the yearly routine ECG, the risk for developing subsequent atrial flutter increased by a factor of 2.1 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934409 TI - Corrected transposition in situs inversus. Biventricular repair of associated cardiac anomalies. AB - Corrected transposition of the great arteries (C-TGA) in situs inversus [I,D,D] is a rare variant of C-TGA (5-8% of the cases). Few anatomic and surgical data on this anomaly have been published. Between 1974 and 1990, 13 such patients (mean age, 12.7 +/- 8.6 yr) underwent repair of associated cardiac anomalies, including ventricular septal defect (VSD) and pulmonary outflow tract obstruction (POTO) in all 13 patients and atrial septal defect (ASD) in 11. Systemic venous anomalies were present in four. Nine patients also had dextrocardia. Patches to close the VSD were placed on the right side of the ventricular septum (through a right [systemic] ventriculotomy) in two patients and on the left side of the ventricular septum in the other 11 via a left ventriculotomy in one or a morphological right (left-sided) atriotomy in 10. The POTO was relieved directly in five patients and bypassed by a left ventricle-pulmonary artery conduit in the other eight. There was one early death due to cerebral hemorrhage. Two patients required a pacemaker for permanent heart block. Other rhythm disturbances included transient heart block in three patients and late atrial fibrillation in one. All the survivors are asymptomatic as late as 15.5 years after the repair. One patient had conduit revision 10.5 years after the initial operation, two had residual POTO of greater than 40 mm Hg, and none had residual VSD. In conclusion, patients with [I,D,D] C-TGA present with a relatively uniform subset of anatomic lesions, including predominantly ASD, VSD, and POTO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934410 TI - Management of thoracoabdominal malperfusion in aortic dissection. AB - Malperfusion of the thoracoabdominal aorta or its branches is a common complication of aortic dissection, often with a fatal outcome. Since 1985 we saw thoracoabdominal malperfusion in 13 patients with aortic dissection. During repair of an acute type A aortic dissection, the intimal flap was fenestrated in three cases in the abdominal aorta and one within the superior mesenteric artery. In two cases with acute type B aortic dissection fenestration was performed at the level of the aortic bifurcation, and in one the descending aorta was replaced. Six patients had chronic dilatation of a false lumen without distal reentry, compromising the true lumen, with malperfusion of viscera, kidneys, and lower extremities. Three patients underwent replacement of the descending aorta, two of them subsequent abdominal aortic replacement with revascularization of the kidneys. One patient had thoracoabdominal replacement, and in two an extra anatomic bypass was implanted. Five patients with acute dissection died: two from sequelae of malperfusion, two of myocardial failure, and one late after stroke. Eight patients are alive 1 month to 5 years after operation. In acute aortic dissection fenestration of the intimal flap may relieve thoracoabdominal malperfusion. In chronic aortic dissection, pseudocoarctation is most likely to occur at the diaphragmatic hiatus. This is treated by replacement of the affected aortic segment. In high-risk patients an extra-anatomic bypass is also feasible. PMID- 1934411 TI - Anatomic repair of Taussig-Bing hearts. AB - From 1978 through 1990, 27 consecutive patients underwent anatomic repair of Taussig-Bing heart (TBH) malformation. Group 1 (seven patients) underwent intraventricular repair by rerouting of the left ventricular blood stream through a tunnel patch from the ventricular septal defect (VSD) to the aorta. Group 2 (20 patients) underwent an arterial switch with VSD closure. Indications for each type of repair were based on the following criteria: when the great vessel relation is more or less anteroposterior, repair is performed at the arterial level; when side by side, the minimal tricuspid pulmonary valve distance is evaluated; if less than aortic valve diameter or if there are abnormal tricuspid chordae, repair is performed at the arterial level; if greater, pulmonary artery banding is performed in order to wait until suitable weight for intraventricular repair. The mean age at operation was 13.2 months. Coarctation of the aorta was present in 12 patients, abnormal tricuspid chords in eight, and subaortic stenosis in seven. The great vessels were in D-transposition in 12 patients, and they were side by side in 15. Seventeen patients underwent previous palliative surgery. Early (two patients, 7.4%) and late (two patients, 8%) mortality rates were related in group 1 to subaortic stenosis and in group 2 to myocardial infarction. Mean follow-up of 40 +/- 24 months was achieved in 22 survivors. They were all in New York Heart Association (NYHA) class I, without medication. Actuarial survival and freedom from reoperation rates were, respectively, at 5 years 73 +/- 14.6% and 58 +/- 13% (70% confidence limits [CL]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934412 TI - Repair of tetralogy of Fallot in infancy. Effect of pulmonary artery size on outcome. AB - The possible influence of small pulmonary artery size on the results following complete repair of tetralogy of Fallot has not been investigated in patients less than 1 year of age. We, therefore, reviewed our recent experience with infant repair to assess this. Between January 87 and October 90, repair was performed in 58 infants less than 1 year old (median, 6 months) with tetralogy of Fallot and pulmonary stenosis (n = 53) or pulmonary atresia without important aortopulmonary collaterals (n = 5). The McGoon ratio (diameter of the right pulmonary artery at the prebranching point plus that of the left divided by the diameter of the aorta at the diaphragm) by cineangiography (n = 48) was between 1.2 and 1.5 in 15 patients, 1.6 and 2.0 in 20, and greater than 2.0 in 13. Transannular patching was performed in 19 of the patients with pulmonary stenosis (36%). Muscle resection was avoided in 29 infants and was minimal in the remaining 29. A weak correlation, with considerable scatter, was found between the McGoon ratio and postrepair right ventricular/left ventricular pressure measured in the operating room (r = 0.4), and the relations were similar to those previously reported for children. Right ventricular/left ventricular pressure was 0.55 +/- 0.03 in infants with McGoon ratios of 1.2-1.5, 0.46 +/- 0.03 with ratios of 1.6-2.0, and 0.47 +/- 0.03 with ratios greater than 2.0 (p = 0.01). There were no hospital deaths, and the 3-year survivorship was 94%. Two infants underwent successful reoperation for residual right ventricular outflow tract obstruction. All other patients are free of significant hemodynamic residua.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934413 TI - Hemodynamic effects of bidirectional cavopulmonary shunt with pulsatile pulmonary flow. AB - The effects of "pulsatile" bidirectional cavopulmonary shunt (BCPS) produced by the flow from the ventricle or Blalock-Taussig (B-T) shunt on ventricular function and pulmonary circulation were evaluated in 10 patients with univentricular heart from 3 to 37 months (mean, 16.6 +/- 9.5 months) after surgery. Age at operation ranged from 7 months to 15 years (mean, 5.5 +/- 4.5 years). In addition to the BCPS, pulmonary flow was supplied from a B-T shunt on the contralateral side of the BCPS in five patients, from the ventricle through the stenotic pulmonary valve in four patients, and from both the ventricle and a B-T shunt in one patient. There were no operative deaths; however, there were two late deaths from acute respiratory infection 10 and 13 months after operation. Mean pulmonary arterial pressure measured the first day after operation ranged from 10 to 19 mm Hg (mean, 14 +/- 3 mm Hg). Mean pulmonary arterial pressure at postoperative cardiac catheterization was less than 15 mm Hg (mean, 12 +/- 4 mm Hg). Pulse pressure ranged from 3 to 12 mm Hg (mean, 7 +/- 4 mm Hg). Arterial oxygen saturation increased significantly from 77 +/- 5% before BCPS to 86 +/- 4% immediately after discharge from the intensive care unit (p less than 0.005) and 85 +/- 3% (p less than 0.025) at late cardiac catheterization. Pulmonary arteriovenous fistula was not detected in contrast echocardiography and pulmonary arteriography. Systemic ventricular end-diastolic volume index decreased significantly (p less than 0.01) from 141 +/- 54 ml/m2 before BCPS to 98 +/- 35 ml/m2 1 month after BCPS by echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934414 TI - Influence of age on results of coronary artery surgery. AB - Coronary surgery is being used increasingly in older and more seriously ill patients. To evaluate the importance of age in predicting complications and mortality after coronary surgery, the results in 13,625 patients undergoing coronary surgery were evaluated. There were 321 patients under the age of 40, 1,758 were 40-49, 4,167 were 50-59, 5,049 were 60-69, 2,184 were 70-79, and 146 were over 80. As patients aged the proportion of women increased, the prevalence of severe angina and congestive heart failure increased, and the severity of the distributions of the coronary stenoses increased. The incidence of the complications of neurological events, wound infections, and death rose in every decade after the age of 40 years. The incidence of death was 0.6% for patients aged 40-49, 1.5% for those aged 50-59, 1.9% for those aged 60-69, 5.0% for those aged 70-79, and 8.3% for those aged 80-89. Advanced age was the most significant independent correlate of neurological events, wound infections, and death. The other multivariate correlates of neurological events were diabetes, hypertension, and, surprisingly, angina class. Again surprisingly, the only other multivariate correlate of wound infections was angina class. The other multivariate correlates of death were emergent surgery, female gender, ejection fraction, severity of coronary disease, diabetes, and a history of congestive heart failure. Of interest, periprocedural Q wave myocardial infarction was independent of age. The most predictive and significant correlate of periprocedural myocardial infarction was emergent surgery; hypertension, absence of a previous myocardial infarction, and a normal ejection fraction were weaker correlates. The ability to predict any complication was relatively weak compared with the ability to predict death. The relative infrequency of coronary surgery over the age of 80 years suggests that there is already strong selection against surgery in octogenarians. In addition, the risk of death, and to some extent other complications, may be predicted in advance based on extensive patient experience. PMID- 1934415 TI - Determinants of early versus late cardiac death in patients undergoing coronary artery bypass graft surgery. AB - Most analyses of risk factors affecting survival after coronary artery bypass graft surgery have not differentiated among factors that influence early and late survival. For this reason, a multiphase model was applied to survival data from 2,967 patients undergoing a first coronary artery bypass graft at the Duke University Medical Center between 1969 and 1984. There were 709 deaths during follow-up to 19.6 years. The data were analyzed using a multivariable survival model that separates the underlying hazard function into as much as three different phases, each incorporating separate risk factors. Two distinct phases were detected. One phase dominated early survival (0-1 year), and the second phase dominated late survival (greater than 1 year). Surgery performed earlier in our experience was associated with elevated risk of dying in both phases but with different magnitudes, whereas lower ejection fraction, greater extent of coronary disease, older age, conduction abnormality, and history of hypertension were associated with elevated risk of dying similarly in both phases (p less than 0.05). Severity of angina symptoms and lower weight were associated with an elevated risk of dying only in the early phase (p less than 0.05; because few of the patients were obese, estimates of the relative risk of morbid obesity could not be estimated), whereas vascular disease, diabetes, and extent of myocardial damage were associated with an elevated risk of dying only in the late phase (p less than 0.05). These data illustrate both the differential influence of risk factors over time and the importance of multiphase models. PMID- 1934416 TI - Surgery extended into the aortic arch in acute type A dissection. Indications, techniques, and results. AB - From May of 1979 to September of 1990, 106 patients underwent emergency surgery for acute type A aortic dissection. In 29 patients (27.3% of total; mean age, 53 years) surgery was extended into the aortic arch. In 19 cases the proximal entry reached or began beyond the aortic cross-clamping site, which prevented proper reconstruction of the distal aorta. In six cases an aortic perforation was located in the arch. In four others the dissection occurred within a preexistent arch aneurysm. Operative techniques consisted of eight arch reconstructions, 17 proximal arch replacements, and four total arch replacements. Repair was performed during deep hypothermia (mean nasopharyngeal temperature, 17.8 degrees C) and circulatory arrest (mean, 24.2 minutes). Operative mortality was 20.6% (six of 29), dropping to 10.5% (two of 19) during the past 4 years. There were no late deaths in the 23 survivors, with one patient suffering from neurological sequelae. Nineteen underwent either computed tomography and digital subtraction angiography or magnetic resonance imaging without pathological findings in the ascending aorta or arch. In acute type A aortic dissection the site of the intimal tear and/or perforation, as well as preexistent aneurysmatic disease, may require primary aortic arch repair. This can be accomplished during deep hypothermia and circulatory arrest, with acceptable early and satisfactory late results. PMID- 1934417 TI - Early and long-term outcome after emergency coronary artery bypass surgery after failed coronary angioplasty. AB - From April 1980 to January 1990, among 2,576 percutaneous transluminal coronary angioplasty (PTCA) procedures, 100 patients (82 men and 18 women; mean age, 54 +/ 10 years [3.9%]) underwent emergency coronary artery bypass graft surgery. Before PTCA 56 had unstable angina, 34 had prior myocardial infarction, and 60 had single-vessel coronary artery disease. The mean time period from the onset of ischemia to surgical reperfusion was 147 +/- 16 minutes; 155 grafts were placed (1.5 grafts per patient). In-hospital mortality was 19%; operative mortality was significantly related to older age (59 +/- 9 versus 53 +/- 10 years, p less than 0.05), presence of unstable angina (74% versus 53%, p less than 0.05), and development of cardiogenic shock or necessity of cardiac massage before surgery (53% versus 16%, p less than 0.0001). In addition, 57 patients developed a Q wave myocardial infarction. For hospital survivors, overall survival at 7 years was 94% (Kaplan-Meier method), with three cardiac deaths during follow-up; two additional patients had late myocardial infarction, and four had late PTCA. At a mean follow-up of 55 +/- 38 months, 78% of the patients had no chest pain, and 80% reported no dyspnea. All patients received antiplatelet agents or oral anticoagulants; 34% had no antianginal medications. Among the 40 previously employed patients, 73% resumed work after surgery. All patients with cardiogenic shock or cardiac massage who survived the initial hospital period were alive at follow-up. After an initial critical period, the long-term clinical outcome of patients with emergency coronary bypass surgery after failed PTCA is satisfactory. PMID- 1934418 TI - Coronary bypass surgery improves survival in high-risk unstable angina. Results of a Veterans Administration Cooperative study with an 8-year follow-up. Veterans Administration Unstable Angina Cooperative Study Group. AB - To identify high-risk subgroups, 468 patients with unstable angina were prospectively stratified according to the clinical presentation of unstable angina (type I or type II) and left ventricular function (normal or abnormal) and were randomized to conventional medical therapy or surgical treatment with coronary bypass surgery. Type I patients (n = 374) were those who had progressive effort angina or recent angina at rest. Type II patients (n = 94) were those who had severe rest angina associated with ST-T changes on the electrocardiogram. Follow-up for 8 years showed that the cumulative mortality rates for type II patients with abnormal left ventricular function were significantly lower in the surgical patients compared with the medical cohorts (13% versus 46%, p less than 0.04). In the other subgroups, cumulative medical and surgical mortality rates were not different. Thus, type II patients with abnormal left ventricular function appear to be the subgroup of patients who are at the highest risk with medical therapy. Coronary bypass surgery significantly reduces the mortality in this high-risk subgroup of patients with unstable angina. PMID- 1934419 TI - Flow-induced vasomotor response to tachycardia of the human internal mammary artery and saphenous vein grafts late following bypass surgery. AB - Increasing blood flow results in endothelium-dependent vasodilation of angiographically normal epicardial coronary arteries in humans. To compare the ability of internal mammary artery (IMA) and saphenous vein (SV) used as coronary artery bypass grafts to adapt their vasomotor tone to an increase in myocardial blood flow demand induced by tachycardia, 10 IMA and seven SV grafts were studied by quantitative angiography more than 6 months (range, 6-82 months) after surgery in 17 patients. All grafts were angiographically smooth and implanted to large nonakinetic perfusion zones. Angiograms were obtained in basal sinus rhythm (71 +/- 10 beats/min), during atrial pacing (129 +/- 9 beats/min), and after intragraft infusion of 1 mg isosorbide dinitrate (ISDN). In basal sinus rhythm, the cross-sectional area of SV was superior to that of IMA (10.7 +/- 3.6 versus 5.4 +/- 1.7 mm2; p less than 0.01). All IMA dilated during pacing (+14.8 +/- 11.5%; p less than 0.005) and a further increase in IMA cross-sectional area occurred after ISDN (+27.4 +/- 20.1% versus basal; p less than 0.005). In contrast, SV failed to dilate during pacing (+0.3 +/- 5.4%; p = NS) and after ISDN (+0.7 +/- 6.0% versus basal; p = NS). Thus, an increase in myocardial blood flow demand induced by tachycardia results in dilation of IMA but not of SV grafted on coronary vessels. The ability of the endothelium to modulate the vasomotor tone of IMA grafts in response to changes in blood flow could contribute to their excellent long-term functional results after coronary artery bypass surgery. PMID- 1934421 TI - Internal mammary artery use. Sternal revascularization and experimental infection patterns. AB - We have described previously the acute sternal devascularization produced by mobilization of one or both internal mammary arteries (IMAs). The present experiments were conducted to examine the time course of sternal revascularization and infection patterns after IMA use. Twenty-four 8-week-old domestic pigs were obtained from a herd in which active Streptococcus faecalis had been detected in recent litters. After control blood flow procedures (microspheres) were completed, each pig underwent a median sternotomy; one or both IMAs were mobilized as a pedicle, and the sternotomy was repaired. Repeat blood flow determinations were made in half the pigs at 1 week and in the remainder after 2 weeks. The pigs were killed, the wound was examined, cultures were taken as indicated, and tissue was harvested for blood flow analysis. Despite the retention of an intact IMA on the contralateral side, persistent, significant sternal ischemia existed 2 weeks after repair. However, when both IMAs were used, the extent of devascularization was exaggerated, and revascularization was impaired further. Revascularization of intercostal muscle occurred more rapidly and was essentially returned to normal 2 weeks after sternotomy and IMA harvest. Active mediastinitis with erosion of the sternum was found in one (17%) of six pigs at 1 week and in four (67%) of six pigs at 2 weeks when the IMAs had been rotated bilaterally. No wound infections were detected in the single IMA resection group. These data suggest that bilateral IMA mobilization may delay an already slow revascularization process and predispose to infectious complications. PMID- 1934420 TI - Influence of diabetes and mammary artery grafting on survival after coronary bypass. AB - The effect of diabetes on survival after coronary bypass surgery is uncertain. Also, although the overall clinical benefits of internal mammary artery (IMA) grafting are well established, the survival benefit attributable to IMA grafting in diabetics is not well characterized. To determine the influence of diabetes and IMA grafting on survival after bypass surgery in the current surgical era, characteristics related to subsequent outcome were analyzed in 5,654 consecutive patients undergoing surgery in the decade of the 1980s. The 1,132 diabetic patients (20%) had more extensive coronary disease, had more left ventricular dysfunction, were older, were more frequently female, received a greater number of grafts (mean, 3.5 versus 3.1), and received more IMA grafts (67% versus 58%) than the 4,522 nondiabetic patients (all p less than 0.001). Overall 5-year survival probability was 0.91 in nondiabetic and 0.80 in diabetic patients (p less than 0.0001). Nondiabetic survival exceeded diabetic survival even in high risk subgroups such as ejection fraction less than or equal to 0.40 (0.80 versus 0.66, p less than 0.02), age greater than or equal to 65 years (0.85 versus 0.73, p less than 0.0003), and, urgent surgery (0.89 versus 0.76, p less than 0.0001). By multivariate analysis, impairment of left ventricular function, advanced age, failure to use an IMA graft, diabetes, female sex, urgent surgery, number of diseased vessels, and mitral insufficiency were incremental risk factors for cardiac mortality (all p less than 0.006). Failure to use an IMA graft and diabetes were equally strong predictors of outcome. Use of an IMA graft conveyed an independent survival benefit to both nondiabetic (p less than 0.0001) and diabetic (p less than 0.02) patients. The magnitude of the survival benefit attributable to IMA grafting in the two groups did not differ (p = 0.4). Diabetes is an important risk factor for late cardiac mortality after bypass surgery and should be included in analyses of the efficacy of therapies for coronary artery disease. IMA grafting conveys a similar benefit to diabetic and nondiabetic patients but does not negate the adverse effect of diabetes on survival. PMID- 1934422 TI - Ischemic cardiomyopathy. Criteria for coronary revascularization and cardiac transplantation. AB - Because of the shortage of donor hearts, 16 (33%) of 48 patients with ischemic cardiomyopathy died awaiting transplantation. Determining factors that predict effective coronary revascularization and identifying patients who may benefit from revascularization is crucial. From 1984 to 1990, 207 ischemic cardiomyopathy patients were evaluated for heart transplantation; 131 were accepted (83 transplanted), 54 were not accepted, and 22 were revascularized (19 underwent bypass graft surgery and three underwent percutaneous transluminal coronary angioplasty). Four bypass patients failed early (less than or equal to 30 days, three deaths and one urgent heart transplant) and two late deaths (greater than or equal to 1 year) occurred. Overall mortality was 27%. Three-year survival of revascularized and transplanted patients was 72 +/- 10% and 73 +/- 6%, respectively. Successfully revascularized patients had preoperative ejection fraction, left ventricular end-diastolic dimension, and New York Heart Association functional class of 26 +/- 9%, 68 +/- 3 mm, and 3.9 +/- 0.4, respectively, compared with 36 +/- 9% (p less than 0.05), 64 +/- 6 mm (p = NS), and 1.2 +/- 0.4 (p less than 0.05) after revascularization. Preoperative ejection fraction of patients failing revascularization was 15 +/- 4% (p = NS compared with successful revascularization), and left ventricular end-diastolic dimension was 81 +/- 4 mm (p less than 0.05). Preoperative positron emission tomography imaging myocardial blood flow and glucose metabolism was performed in 12 patients: 10 patients with scans predicting reversible ischemia were successfully revascularized, and two patients with negative scans had failed revascularization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934423 TI - Survival improvement with dynamic cardiomyoplasty in patients with dilated cardiomyopathy. AB - Surgical support to the failing heart has been investigated in the treatment of severe myocardial failure. Dynamic cardiomyoplasty was indicated in 32 patients with dilated or chagasic cardiomyopathy who were in New York Heart Association (NYHA) class III or IV despite maximum medical therapy. Fifteen patients were operated on, and 17 refused the surgical treatment and were maintained by clinical means. With an average follow-up period of 12.3 months, actuarial survival rates for cardiomyoplasty patients were 86.6% at 6 months, 78.7% at 1 year, and 65.6% at 2 years of follow-up, whereas patients under medical therapy presented survival rates of 58.8%, 41.1%, and 27.4% at the same periods, respectively (p = 0.03). Furthermore, five of the 11 surviving patients of the cardiomyoplasty group are in NYHA class I, five in class II, and one in class III. At 6 months of cardiomyoplasty follow-up, rest radioisotopic left ventricular ejection fraction increased from 20.1 +/- 3.9% to 26.8 +/- 7.5% (p less than 0.01). Cardiopulmonary exercise testing showed that maximum oxygen consumption during treadmill testing improved from 14.7 +/- 3.9 to 18.3 +/- 3.9 ml/kg/min (p = 0.01). At 1 year of follow-up, these data remained essentially unchanged. In conclusion, dynamic cardiomyoplasty reverses congestive heart failure and improves the long-term survival of patients with severe cardiomyopathies. PMID- 1934424 TI - Long-term survival and complications after composite graft replacement for ascending aortic aneurysm associated with aortic regurgitation. AB - The Bentall operation was performed in 44 patients between March 1972 and December 1988. Twenty patients had stigmata of Marfan's syndrome, and 15 had aortic dissection. All showed annuloaortic ectasia. Follow-up ranged from 1 to 16 years (mean, 5.8 years). There were six early deaths (14%) and seven late deaths (16%), with actuarial survival at 10 years of 65 +/- 8%. The late deaths were mostly related to aneurysms occurring in the remainder of the aorta. No patient has undergone reoperation related to the composite graft, but six patients required seven subsequent operations on the remaining aorta. The actuarial probability of freedom from late death and subsequent operation at 8 years was 64 +/- 9% for the operative survivors, but it was 44 +/- 17% for the patients with aortic dissection and 37 +/- 19% for those with Marfan's syndrome. Postoperative angiography performed 3-168 months (mean, 42 months) postoperatively in 23 nonselective patients demonstrated recurrent true aneurysms at both or one of the coronary ostia (seven), persistent dissection distal to the distal aortic anastomosis (five), pseudoaneurysm at the left coronary ostium (one), pseudoaneurysm due to a small leak at the proximal aortic anastomosis (one), and partial dehiscence of the distal aortic suture line (one). Composite graft replacement carries a potential risk of various late complications. Our data support the concept that earlier detection and aggressive treatment of the late complications occurring in the remainder of the diseased aorta is necessary to improve long-term survival after the Bentall operation. PMID- 1934425 TI - Surveillance for rejection by echocardiographically guided endomyocardial biopsy in the infant heart transplant recipient. AB - Echocardiographically guided endomyocardial biopsy via percutaneous right internal jugular vein puncture has been performed 98 times in six patients 5-16 years of age at our institutions. The use of this approach was extended for rejection surveillance in seven infants transplanted at 2 weeks to 15 months of age (median, 2 months; mode, 2 weeks). A total of 35 consecutive biopsies were performed under heavy sedation in these infants (lowest weight, 3.0 kg) with the use of a 5F semirigid bioptome through a 5.0-cm 5F sheath. There was no case of entrance failure. A median of four biopsies was performed on each child (range, one to 14). Four to seven tissue pieces per biopsy were obtained using an apical four-chamber view for bioptome guidance. Ten instances of clinically suspected rejection were not confirmed by biopsy, and two cases of unsuspected rejection were found. The only complication was one instance of new mild tricuspid regurgitation in this group compared with one instance of increased tricuspid regurgitation after biopsy in the older child group. These preliminary results suggest that echocardiographically guided endomyocardial biopsy from the right internal jugular approach is a reliable and safe means for rejection surveillance in the infant and young child. PMID- 1934426 TI - Improved heart preservation with University of Wisconsin solution: experimental and preliminary human experience. AB - We tested the ability of University of Wisconsin solution (UWS) to extend hypothermic nonperfused heart preservation in baboons and then proceeded to human transplantation. Orthotopic transplantation was performed in five baboons (UWS cardioplegia and storage [4 degrees C]; preservation time 10.3 +/- 0.6 hours). Four survivors were immunosuppressed for 45 days and killed. One animal died from disruption of the aortic anastomosis due to technical error. Preservation did not alter histology under light and electron microscopy or heart weight (at harvest, 51.4 +/- 11.6 g; before implant, 52.5 +/- 11.1 g). Animals were weaned from bypass (mean, 23 +/- 12 minutes) and returned to their cages without intravenous support within 3.6 +/- 0.6 hours. Weekly biopsy, electrocardiogram, enzyme analysis, echocardiogram, and right heart catheterization demonstrated excellent cardiac function. Following success in baboons, UWS was applied to human transplantation (n = 2, UWS cardioplegia and storage [4 degrees C]; preservation time 4.2 and 2.1 hours). The hearts returned to sinus rhythm within 4 minutes of reperfusion without defibrillation, and enzymatic and hemodynamic data reveal excellent heart preservation. Preliminary data suggest the ability of UWS to prolong heart preservation in baboons and be used safely in humans. Further studies are required to compare UWS with crystalloid cardioplegia and saline storage and to prolong donor heart preservation in humans. PMID- 1934427 TI - The influence of preoperative patient characteristics on early and late survival following cardiac transplantation. AB - In an attempt to identify the preoperative factors that influence survival following cardiac transplantation, we retrospectively analyzed multiple demographic, clinical, and hemodynamic data of 301 consecutive patients who underwent cardiac transplantation between December 1980 and July 1988 (cyclosporine era). Univariate and multivariate regression analyses revealed that the two most deleterious risk factors for premature death following transplantation were pulmonary hypertension not responsive to vasodilator challenge and preoperative requirement of hemodynamic support (intravenous inotropes or mechanical assistance). The combination of these two independent risk factors was an even stronger predictor of mortality (relative risk, 6:1; p less than 0.0001): the 3-month actuarial survival rate of the 20 patients with this combination was 30.3% versus 78.4% of the 47 patients with only pulmonary hypertension, 87.9% of the 42 patients with only the requirement of hemodynamic support, and 95.3% of the 172 patients with neither of these two risk factors. The difference in postoperative mortality between patients with versus those without these two risk factors is due to a higher rate of fatal infectious complications: six of 20 patients (30%) with both risk factors died from infection within 3 months after transplant compared with three deaths among 172 patients (1.7%) with neither of these risk factors. The majority of fatal infections were pulmonary. There were significantly more fatal and nonfatal infectious episodes in patients with one or both of these risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934428 TI - Progression of systemic disease and reduced long-term survival in patients with cardiac amyloidosis undergoing heart transplantation. Follow-up results of a multicenter survey. AB - Amyloid heart disease has been considered a contraindication for cardiac transplant based on the hypothesis that it is a systemic disease and that amyloid deposition would occur in the cardiac allograft. A survey was sent to all of the US centers and a limited number of Canadian and European centers listed with the International Registry. Twenty-four centers responded, and data were ultimately provided for a total of 10 patients (3 men, 7 women, mean age 48 years, range 30 60 years) who were transplanted for cardiac amyloid. The diagnosis of cardiac amyloidosis was made histologically on endomyocardial biopsy and/or examination of the explanted heart. Additional documented organ involvement included liver (two of 10), rectal (three of 10), renal (two of 10), gingiva (two of 10), and tongue (one of 10), although invasive biopsies were not performed in a majority of patients. A specific amyloid protein was identified in eight patients (seven lambda, one kappa immunoglobulin light chain). Although four of the surviving nine patients (one perioperative death) developed recurrent amyloid deposition in the allograft, it was detected solely by electron microscopy in two of these and had no clinical significance. There was, however, a progressive risk of major organ involvement with organ function impairment in this group (22% at 12 months, 50% at 24 months, 66% at 48 months). Although the immediate and early postoperative outcomes were not dissimilar between this group and patients undergoing transplantation for other cardiac diseases, late survival was reduced (39% at 48 months) compared with the larger population, but differences were not statistically significant due to the small amyloid sample size (p = 0.16).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934429 TI - Influence of activation origin, lead number, and lead configuration on the noninvasive electrophysiologic detection of cardiac allograft rejection. AB - An improved method of cardiac allograft surveillance, less invasive than endomyocardial biopsy (EMB), is required as the scope of cardiac transplantation increases. The correlation between changes in telemetrically recorded intramyocardial electrograms and the degree of rejection was examined. The electrophysiological parameter assessed was the unipolar peak-to-peak amplitude (UPPA), defined as the magnitude of the first, fast negative deflection of the QRS complex in unipolar electrograms. A canine model of intrathoracic heterotopic cardiac transplantation was employed in which each graft was instrumented with four unipolar intramyocardial electrodes (two left ventricle [LV] and two right ventricle [RV]) connected to two telemetric pacemakers. Immunosuppression was begun at operation and continued for a variable period of time following the acquisition of control data (postoperative days 6-10). Graft status was monitored via biweekly EMB. Intramyocardial electrograms were recorded from each lead during sinus rhythm and 36 atrial and ventricular pacing protocols on a daily basis. The daily UPPA was calculated for each rhythm sequence and expressed as percent of control UPPA. EMBs were qualitatively graded and assigned a quantitative rejection score (0 = none; 3 = severe). Criteria for rejection were rejection score (RS) greater than or equal to 0.66 or daily UPPA less than 85% control. Eight animals were included for study and, in all animals, rejection was documented. A total of 30 EMBs were obtained; in 11 EMBs rejection was present by histological criteria. Analysis of grouped UPPA data from all four leads revealed a sensitivity and specificity of 91% and 84%, respectively, in the detection of rejection. Analysis of grouped sinus UPPA data from the two LV leads revealed a sensitivity of 94% and 91%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934430 TI - Detection of lung rejection with indium-111-labeled lymphocytes in heterotopic rat heart-lung transplantation. AB - To determine if acute lung rejection after heart-lung transplantation can be detected noninvasively with indium-111-labeled (111In) lymphocytes, we studied 33 allogeneic and 18 isogeneic heterotopic heart-lung transplants in rats. Twenty four hours after injection of isogeneic splenic 111In-lymphocytes (75 +/- 2 microCi/100 million cells), animals were scanned at 2 to 8 days after transplant (Tx). Also, percent indium uptake of the graft was determined and compared with pathologic lung changes. Between the vascular and destructive phases of lung rejection, 111In-lymphocyte uptake of lung allografts was significantly greater than isografts (p less than 0.001). Lung allografts in the alveolar phase (4-6 days after Tx) showed the most intense uptake (2.7 +/- 0.1%) of injected 111In lymphocytes. All scintigrams of allografts from the late vascular to the early destructive phase (3-7 days after Tx) showed visualization of the lung graft (27/27 true positive, sensitivity = 100%). In contrast, lung isografts of the same period showed no pathological sign of rejection and were only rarely visualized (12/14 true negative, specificity = 86%). Lung rejection may be accurately assessed noninvasively by gamma scintigraphy with 111In-lymphocytes. This technique may prove useful in the detection of acute lung rejection in human heart-lung transplant recipients. Modification of the labeling dose chosen may further improve scan accuracy. PMID- 1934431 TI - High-frequency jet ventilation improves cardiac function after the Fontan procedure. AB - Pulmonary vascular resistance is an important determinant of cardiac output after the Fontan procedure and is adversely affected by elevated mean airway pressure. High-frequency jet ventilation (HFJV) is an alternate form of mechanical ventilation which supports gas exchange at lower mean airway pressure. This study was performed to determine if HFJV could lower mean airway pressure and pulmonary vascular resistance and result in an increase in cardiac output after the Fontan procedure. We prospectively evaluated 13 patients ranging in age from 0.9 to 8.5 years (mean, 3.9 years) and in weight from 6.2 to 20.1 kg (mean, 13.9 kg). Right atrial, left atrial and pulmonary artery catheters were used to measure hemodynamic parameters. Cardiac index was measured by dye dilution technique, and pulmonary vascular resistance was calculated. The patients were stabilized on mechanical ventilation to achieve a PaCO2 = 30 +/- 5 mm Hg, and baseline hemodynamic and respiratory measurements were made. HFJV was begun at settings adjusted to achieve similar gas exchange. Respiratory and hemodynamic measurements were repeated after 30-60 minutes of HFJV. Mechanical ventilation was then resumed at baseline settings, and measurements were repeated 0.5-1 hour later. There was no significant change in gas exchange. HFJV resulted in a 50% reduction in mean airway pressure (9.2 +/- 0.2 cm H2O to 4.6 +/- 0.1 cm H2O, p less than 0.001), a 59% reduction in pulmonary vascular resistance (3.82 +/- 0.36 to 1.52 +/- 0.16 Woods units, p less than 0.001), and a 25% increase in cardiac index (2.32 +/- 0.12 l/min/m2 to 2.91 +/- 0.12 l/min/m2, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934432 TI - Preconditioning the heart by repeated stunning improves myocardial salvage. AB - Repeated regional ischemia of short duration followed by reperfusion leads to preconditioning of the myocardium. Left anterior descending coronary artery (LAD) occlusion was applied for 5 minutes and then released for 10 minutes. This was repeated four times by using an intact pig model. LAD occlusion was then continuously applied for 1 hour. Myocardial function, high energy phosphates, and membrane phospholipids were compared with a control (nonstunned) group over a 6 hour reperfusion period. Stunning itself produced no significant change in regional function, total phospholipids, or free fatty acids (FFA). However, regional function, adenosine triphosphate, and creatine phosphate were significantly (p less than 0.05) reduced over control. After 60 minutes of ischemia, regional function was significantly improved by preconditioning that persisted throughout reperfusion (p less than 0.01). This was associated with an 11% mean decrease in infarct size (p less than 0.05). Adenosine triphosphate was significantly preserved during ischemia in the preconditioned hearts, and this preservation persisted throughout reperfusion (p less than 0.05). Total phospholipids were not affected by ischemia in either group. However, during reperfusion both groups demonstrated a 15-20% decrease in phospholipid levels at 1 hour, with only the stunned group showing a progressive increase at 3 and 6 hours (p less than 0.05). Examination of FFA during reperfusion demonstrated a profound increase in only the unstunned animals (p less than 0.05), correlating with the decreased level of membrane phospholipids noted in this group. In conclusion, repeated stunning predisposes the heart to recovery after regional ischemia. This results in improved mechanical function, increased high-energy phosphate stores, and decreased infarct size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934433 TI - Comparison of different types of cardioplegia and reperfusion on myocardial metabolism and free radical activity. AB - Current techniques of myocardial protection during global ischemia include hypothermia, cardioplegic arrest and controlled reperfusion. To compare different types of cardioplegia and reperfusion techniques we measured the levels of adenine nucleotides and malondialdehyde (MDA, as free radical activity) in 33 patients undergoing heart surgery. The patients were randomized in three groups according to the characteristics of cardioplegia and reperfusion: cold blood cardioplegia with unmodified blood reperfusion (control group, 11 patients), crystalloid cardioplegia and reperfusion (Hopital Lariboisiere protocol, 11 patients) and crystalloid cardioplegia with allopurinol enriched blood reperfusion (Hopital Broussais protocol, 11 patients). Myocardial biopsy specimens were obtained before cardioplegic arrest (preischemic values), at the end of ischemia and after 30 minutes of reperfusion. Biopsy specimens were analyzed by high performance liquid chromatography for levels of adenine nucleotides and MDA. In the three groups, the preischemic values of adenine nucleotides and MDA were not significantly different. For AMP and ADP concentrations neither treatment nor biopsy-time effects appeared. ATP concentration decreased significantly with biopsy-time without specific treatment effect. For MDA concentration neither treatment nor biopsy-time effects were observed. This study suggests that there is no statistically significant difference between any of the three cardioplegia and reperfusion techniques for either ATP or MDA; the three reperfusion techniques limit the free radical activity but do not prevent the fall in high energy phosphates. PMID- 1934435 TI - Effect of rapid cooling contracture on ischemic tolerance in immature myocardium. AB - Hypothermic perfusion before cardioplegic ischemic arrest is commonly used in neonatal cardiac surgery. However, perfusion cooling of the heart in the nonarrested state results in an inotropic response and may induce myocardial contracture secondary to a sustained elevation of intracellular calcium levels. The effect of prearrest cardiac cooling was examined in two groups of isolated parabiotic, blood-perfused neonatal rabbit hearts. Group C (cooling group, n = 12) was exposed to 15 minutes of cold perfusion to 12 degrees C before 1 hour of cardioplegic arrest. Group N (normothermia group, n = 11) underwent identical arrest conditions but without prearrest cold perfusion. Developed pressure at constant volume in group C fell from 109 +/- 8.7 mm Hg at baseline to 55.2 +/- 5.5 mm Hg after 30 minutes of reperfusion versus no significant change in group N. Diastolic compliance showed significant deterioration in group C, with marked elevation of diastolic pressure from 9.8 +/- 0.4 mm Hg at baseline to 22.0 +/- 4.4 mm Hg after ischemia and reperfusion. This experimental data demonstrates that profound hypothermic perfusion of the myocardium in the nonarrested state may induce a rise in resting myocardial tension and that cardioplegic ischemic arrest in the presence of cooling contracture may result in important myocardial injury. PMID- 1934434 TI - Optimal delivery of blood cardioplegia. AB - A prospective randomized controlled trial was performed to determine optimal flow rates and hemoglobin concentrations for continuous normothermic blood cardioplegia and to compare warm heart surgery with standard intermittent cold blood cardioplegia. Thirty-five patients received intermittent cold blood cardioplegia, low hemoglobin low flow, low hemoglobin high flow, high hemoglobin low flow, or high hemoglobin high flow warm blood cardioplegia (seven patients per group: low hemoglobin, 50 g/l; high hemoglobin, 80 g/l; low flow, less than 80 ml/min; high flow, greater than 80 ml/min). Hypothermia resulted in a significantly greater accumulation of ADP and AMP during cross clamp, consistent with impaired mitochondrial function. Low hemoglobin low flow warm blood cardioplegia increased myocardial oxygen consumption and coronary sinus blood flow after cross clamp release, and also decreased lactate consumption. Postoperative myocardial performance and diastolic compliance were reduced in low hemoglobin low flow warm patients, and diastolic compliance was increased with high hemoglobin high flow warm blood cardioplegia when compared with cold patients. In this study, continuous normothermic cardioplegia was safe when delivered at 80 ml/min or greater, with a hemoglobin concentration of at least 80 g/l, affording myocardial metabolic and functional recovery comparable to that found after intermittent cold blood cardioplegia. PMID- 1934436 TI - Age-related response to epinephrine-induced myocardial stress. A functional and ultrastructural study. AB - Left ventricular systolic and diastolic function before, during, and after a 2 hour intravenous infusion of epinephrine at either 0.5 micrograms/kg/min or 2 micrograms/kg/min were assessed by pressure-volume data obtained by conductance catheter micromanometer technique and correlated with cardiac ultrastructure and plasma levels of epinephrine in neonatal (3-5 days old, n = 12) versus adult (3-4 months old, n = 11) pigs. Administration of epinephrine at 0.5 micrograms/kg/min resulted in an increase in end-systolic elastance (Ees) only in adults, whereas at 2.0 micrograms/kg/min Ees increased in both groups. After 2-hour administration of epinephrine at 2.0 micrograms/kg/min, Ees decreased significantly (p less than 0.05) from the preinfusion baseline value of 8.9 +/- 2 (mean +/- SD) to 5 +/- 1.7 mm Hg/ml, and a significant (p less than 0.05) increase in left ventricular volume elasticity (VdP/dV) from 0.4 +/- 0.02 to 1.4 +/- 0.2 mm Hg occurred in neonates versus no change from baseline in either Ees or VdP/dV in the adults. These changes in the neonates were associated with sarcolemmal rupture and mitochondrial Ca2+ granule deposition versus normal cardiac ultrastructure in the adults. We conclude that the neonatal myocardium is more susceptible to cardiotoxicity from circulating epinephrine. PMID- 1934437 TI - Traumatic rupture of the thoracic aorta. A 20-year review: 1969-1989. AB - Acute traumatic injury of the thoracic aorta is a relatively common injury of deceleration accidents, usually high-speed motor vehicle accidents. The limiting factor to successful hospital management of these victims is early diagnosis and prompt treatment. Between the years 1969 and 1989, 116 patients (87 men and 29 women) were diagnosed with acute traumatic injury of the aorta. The mean age was 38.8 years, and the range was from 11 to 82 years. All patients who presented to the hospital emergency departments were included in the evaluation. The diagnosis of aortic rupture was firmly established by either aortography, surgery, or autopsy. The site of injury in 105 (90.5%) was the aortic isthmus, that is, distal to the origin of the left subclavian artery. In nine patients (7.7%) the injury was in the distal thoracic aorta. Two patients had injuries of the aortic arch. Associated injuries were present in 110 patients (95%); 16 patients (14%) had no external evidence of chest injury. Only 50 patients (43%) had the opportunity for definitive surgical management. The nonsurgical group comprised 66 patients (57%), and all of these died; the cause of death was unsuspected, suspected, or diagnosed after hospital admission from the emergency department. Of the surgical group, 36 patients (72%) survived, whereas 14 patients (28%) died. The surgical management comprised partial cardiopulmonary bypass in 31 patients that included seven deaths, simple aortic cross-clamping in 14 that included six deaths, and nonheparinized bypass in four that included one death. The incidence of paraplegia was 3.2% (one patient) with cardiopulmonary bypass, 28.5% (four patients) with simple aortic cross-clamping and none with nonheparinized bypass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934439 TI - Role of percutaneous bypass in reducing infarct size after revascularization for acute coronary insufficiency. AB - This study compares the effectiveness of percutaneous bypass (PB) with that of the intra-aortic balloon pump (IABP) in reducing infarct size and ischemic damage after revascularization for acute coronary occlusion. In 30 adult pigs, the second and third diagonal vessels were occluded with snares for 1 1/2 hours, followed by 1/2 hour of cardioplegic arrest and 3 hours of reperfusion with the snares released. During the period of coronary occlusion before the institution of cardiopulmonary bypass, 10 pigs were placed on PB, 10 pigs received IABP, and 10 others received no intervention (unmodified). Ischemic damage in the area at risk was assessed by echo wall motion scores (ranging from 4 indicating normal to -1 indicating dyskinesia), changes in myocardial tissue pH (delta pH) from preischemia, and the area of necrosis/area of risk (AN/AR) ratio. Hearts treated with the IABP had the highest wall motion scores (1.27 +/- 0.33 for unmodified versus 1.40 +/- 0.30 for PB versus 2.04 +/- 0.30 for IABP), the least change in pH values from preischemia (delta pH: 0.41 +/- 0.13 for unmodified versus 0.60 +/ 0.10 for PB versus 0.25 +/- 0.09 for IABP, p less than 0.05 for IABP versus PB), and the least amount of myocardial necrosis (AN/AR ratio: 73 +/- 4% for unmodified versus 43 +/- 2 for PB versus 27 +/- 4 for IABP, p less than 0.05 for PB and IABP versus unmodified and for IABP versus PB). Although the PB group experienced less myocardial necrosis than did the unmodified group, the most optimal recovery occurred in the IABP group. PMID- 1934438 TI - Amiodarone-related postoperative adult respiratory distress syndrome. AB - Directed surgical intervention in patients with ventricular tachyarrhythmias who have experienced failure of amiodarone therapy is a common clinical scenario. Sixty-seven patients with malignant ventricular tachyarrhythmias received either an automatic implantable cardioverter-defibrillator (n = 43) or subendocardial resection (n = 24). Nineteen cardiothoracic procedures (automatic implantable cardioverter-defibrillator in six, endocardial resection in 13) were performed in 17 patients who received amiodarone before surgery. Eight received the drug acutely as a loading dose of 1,200 mg/day for 7-14 days; 11 patients were on chronic oral amiodarone at a mean dose of 362 +/- 74 mg/day. Eight patients were removed from amiodarone therapy a mean of 6.6 days before surgery. Adult respiratory distress syndrome (ARDS) developed after surgery in nine (50%) of 18 surgical survivors. ARDS was manifested by hypoxemia, pulmonary infiltrates, and prolonged intubation. Pulmonary capillary wedge pressure and cardiac output were measured before and after surgery and during ARDS. Pulmonary capillary wedge pressure and cardiac output remained constant after surgery at a time that the PaO2/FIO2 ratio fell significantly. By contrast, none of the remaining 44 patients who did not receive amiodarone developed ARDS despite similar preoperative and intraoperative clinical parameters. Patients with ventricular tachyarrhythmias who receive even a short course of amiodarone are at risk for postoperative ARDS. PMID- 1934440 TI - A prospective randomized study of a modified technique of ultrafiltration during pediatric open-heart surgery. AB - Conventional ultrafiltration (UF) fails to reverse satisfactorily hemodilution and the rise in total body water (TBW) seen after cardiopulmonary bypass (CPB). We have modified the technique, timing, and placement of UF in the CPB circuit and in pilot studies observed controlled elevation of hematocrit and a significantly reduced rise in TBW. We have carried out a prospective randomized study in 50 children undergoing open-heart surgery, comparing modified UF (MUF) with nonfiltered controls. MUF was carried out for 10 minutes after completion of CPB to a hematocrit of 36-42. Fluid balance, TBW (by bioimpedance), and hemodynamics were recorded for 24 hours postoperatively. The results were analyzed using Mann-Whitney U test, comparing controls (n = 24) to ultrafiltered (n = 24). There was one death in each group. Blood loss (ml/kg/24 hr) was 19.5 median (range, 9-30) in the controls versus 12.5 (8-22) in MUF (p = 0.0002); blood transfused (ml/kg/24 hr) 15.5 (3-35) in controls versus 3 (0-11) in MUF (p = 0.0001); colloid transfused (ml/kg/24 hr) 12 (6-56) in controls versus 12 (0 28) in MUF (p = 0.18); percent rise in TBW 11.1 (4.3-16.8) in controls versus 4.0 (1.6-7.9) in MUF (p = 0.0001). There was rise in arterial blood pressure during MUF. Percent rise of systolic blood pressure was 1 (-4 to +9) in controls versus 49 (5-81) in MUF (p = 0.0001); percent rise in diastolic blood pressure 0 (-5 to +8) in controls versus 28 (3-47) in MUF (p = 0.0001). UF reduced the rise in TBW and donor blood requirement associated with CPB in children. The blood pressure rise observed during UF is as yet unexplained, but if proven safe the technique may permit donor blood-free cardiac surgery and prevent the accumulation of potentially dangerous excess tissue fluid. PMID- 1934441 TI - Intraoperative ultrasonographic evaluation of the ascending aorta in 100 consecutive patients undergoing cardiac surgery. AB - Dislodgement of atheromatous plaque from the ascending aorta following manipulation is one of the principal causes of stroke following cardiac surgery. To define clinical correlates that predict the presence of severe atherosclerosis, we performed ultrasonographic evaluation of the ascending aorta at the time of cardiac surgery in 100 consecutive patients. The ascending aorta was divided into three equal segments for analysis, and the severity of atherosclerosis was determined as mild when intimal thickening (less than 3 mm) was localized to one segment, moderate when intimal thickening (greater than 3 mm) was present in one or two segments, and severe when intimal thickening (greater than 3 mm) was present throughout the entire circumference in all three segments. Thirty-eight percent of the studies were normal, mild atherosclerosis was present in 33%, moderate atherosclerosis in 19%, and severe atherosclerosis in 10% of the patients. Palpation of the ascending aorta to detect atherosclerosis significantly underestimated the presence (p less than 0.001) and severity (p less than 0.001) of atherosclerosis when compared with ultrasonography. Age, carotid artery disease, diabetes, gender, smoking, and hypertension were evaluated for their ability to discriminate between normal and severely atherosclerotic aortas. Stepwise logistic regression analysis showed age (p less than 0.02) and diabetes (p less than 0.04) to be significant independent predictors of the presence of severe atherosclerosis in the ascending aorta. Based on the ultrasonographic findings, the operative procedure was altered to reduce the risk of embolization in 17% of the patients. We conclude that high resolution images of the ascending aorta for identification of atherosclerosis can be obtained by ultrasonography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934442 TI - Dobutamine-201Tl imaging. Assessing cardiac risks associated with vascular surgery. AB - The prevalence of coronary artery disease among patients considered for vascular surgical reconstructive procedures is appreciable though often clinically not apparent. One hundred and twenty-six patients underwent dobutamine-201Tl imaging (DTI) in preparation for vascular reconstruction. Fifty-four patients (43%) had a normal study and underwent vascular reconstruction, with one postoperative myocardial ischemic event (1.8%). 30 patients (24%) had a fixed defect present on DTI, which was indicative of prior infarction. Twenty-eight of these 30 patients underwent vascular reconstruction, with three postoperative myocardial ischemic events (11%, p = NS). The presence of a fixed defect on DTI did not significantly increase the risk of ischemic events in patients undergoing vascular procedures. Forty-two (33%) patients had reperfusion of their defects on DTI, which was indicative of myocardial ischemia. Fifteen of these 42 (36%) were denied vascular reconstruction. Nine of the 42 (21%) had either coronary artery bypass graft surgery or coronary angioplasty performed before vascular reconstruction without any postoperative myocardial ischemic events. The remaining 18 patients with reversible ischemia identified by DTI underwent vascular reconstruction without preoperative cardiac intervention, and nine of these 18 (50%) suffered a postoperative myocardial ischemic event (p less than 0.0001). Although there was a difference in the incidence of ischemic events among patients undergoing peripheral vascular compared with aortic reconstruction (71% versus 36%), if there was reversible ischemia identified on DTI this did not reach statistical significance. DTI is a reliable screening test that allows for an accurate means of predicting cardiac risks associated with vascular reconstruction, as well as identifying patients that might benefit from further cardiac evaluation and preoperative intervention. PMID- 1934443 TI - Adjusting anticoagulation to prosthesis thrombogenicity and patient risk factors. Recommendations for the Medtronic Hall valve. AB - In order to determine optimum anticoagulation levels for the Medtronic Hall valve, the effect of low anticoagulation (mean International Normalized Ratio [INR] 2.5, 1979-1984) and moderate anticoagulation (mean INR 3.0, 1985-1989) was determined in 345 patients (183 low, 162 moderate) undergoing isolated mitral valve replacement (MVR) and 241 patients (91 low, 150 moderate) undergoing isolated aortic valve replacement (AVR). There were no cases of valve thrombosis. Embolic events and bleeding events were graded in severity and multiple decrement event-free survival calculated according to valve site and anticoagulation level: MVR low, MVR moderate, AVR low, and AVR moderate. In the MVR low group, 80% were free of all events and 93% free of serious events at 3 years compared with 89% and 98%, respectively, in the MVR moderate group. The AVR low group experienced a very small incidence of embolic events (one only) and no bleeding events. The AVR moderate group suffered more bleeding and more embolic events and at 3 years only 87% were event-free compared with 99% in the AVR low group. In both AVR groups, all embolic events were associated with one or more known stroke risk factors. Patients under 70, in sinus rhythm who were normotensive and were nonsmokers suffered no embolic events irrespective of their anticoagulation level. We conclude that the optimum INR for the average Medtronic Hall patient is 3.0 after MVR and 2.5 after AVR but some adjustments may be required in relation to stroke risk factor analysis. PMID- 1934444 TI - Prognosis of patients with medically treated aortic dissections. AB - The purpose of this study is to evaluate the long-term results of medical treatment for a dissecting aorta and to detect the risk factors that determine the prognosis of medically treated patients. During the past 10 years, 228 patients with aortic dissections were admitted to our hospital and affiliated hospitals. One hundred thirty-four patients, including 60 with proximal type (Stanford, type A) and 74 with peripheral type (Stanford, type B) dissections, were treated by medical means alone. The survival rates of medically treated patients with type A dissections at 24 hours, 2 weeks, and 5 and 10 years after the onset of the disease were 72, 43, 34, and 28%, respectively, and the survival rates in type B dissections were 100, 92, 76, and 56%, respectively. The risk factors that determine poor prognosis in the acute phase of dissections were type A dissection and serious complications (rupture of the aorta, shock, cerebral accident, myocardial infarction, severe aortic regurgitation, renal failure, mesenteric infarction, and arterial occlusion in the extremities). The risk factors in the chronic phase were serious complications, excluding shock and rupture in the acute phase, the large diameter of the dissecting aorta, and increasing age. These results show that emergency surgical intervention is indicated in the patients with acute type A dissections and in those who had acute type B dissections with these serious complications. Medical treatment may be tentatively recommended for the patients with uncomplicated type B dissections until the operative death rate in these patients becomes less than presently identified. PMID- 1934445 TI - Mechanical cardiac valve thrombosis. Is thrombectomy justified? AB - To determine the incidence and results of the treatment offered to acute thrombotic obstructions of mechanical valvular prostheses, we have reviewed a series of 3,637 consecutive hospital survivors who, between January 1970 and September 1990, underwent single mitral or aortic and double mitroaortic valve replacements (MVR, AVR, and DVR, respectively). The cumulative follow-up in these patients was 22,783 years (mean, 7.2 years; range, 0.6-19 years). Sixty-five patients (24 MVR, 13 AVR, and 28 DVR) experienced 72 thrombotic prosthetic obstructions (42 mitral and 41 aortic prostheses) at a mean interval of 3.4 years (range, 0.6-14 years) after the operation. The actuarial prosthetic thrombosis free estimates were 96 +/- 0.9% for MVR, 97 +/- 0.9% for AVR, and 96 +/- 0.8% for DVR (all NS). Mortality associated with prosthetic thrombosis was 25% (four in the MVR group, five in the AVR group, and seven in the DVR group). Fifty-seven patients (22 MVR, 12 AVR, and 23 DVR) underwent a total of 62 reoperations, with a hospital mortality of 17% (two MVR, four AVR, and four DVR). In 37 of the latter patients (20 MVR, three AVR, and 14 DVR), we performed valve replacement (31 mitral prostheses and 14 aortic prostheses), with a hospital mortality of 16% (six of 37) and only one case of subsequent rethrombosis (actuarial rethrombosis free estimate, 96 +/- 3.6%). Conversely, five of the 27 patients (actuarial rethrombosis free estimate, 41 +/- 20%) (two MVR, 11 AVR, and 14 DVR) (seven mitral prostheses and 21 aortic prostheses) whose prosthetic valves were debrided developed rethrombosis during follow-up (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934446 TI - Prediction of aortic annulus diameter by two-dimensional echocardiography. Application in the preoperative selection and preparation of homograft aortic valves. AB - The preoperative selection and preparation of an appropriately sized homograft aortic valve would allow delay of surgery if a suitable valve were unavailable, thus pre-emptying inventory limitations, and a decrease of ischemic time in cases of isolated aortic valve replacement. An accurate preoperative measurement of the aortic annulus diameter is the prerequisite for such selection. The aortic annulus diameter was measured retrospectively in a blinded fashion from the two dimensional echocardiograms of 62 patients who underwent aortic valve replacement with mechanical or bioprosthetic valves. Measurements were obtained with electronic calipers by two observers. Confidence in the accuracy of the measurement obtained was ranked on a scale from 1 to 5. The mean difference between echocardiographic measurements and prosthetic valve sizes was 0.39 +/- 0.46 mm (mean +/- 2SD) for observer 1 and -0.26 +/- 1.44 mm for observer 2. Ninety-eight percent of observer 1 measurements and 80% of observer 2 measurements were within 1.5 mm of the prosthetic valve size (p less than 0.01 for differences between observers). Confidence scores were higher for observer 1 and for both observers were related to accuracy. The aortic annulus diameter of eight patients scheduled for homograft aortic valve replacement was measured prospectively with the same technique. There was an excellent agreement between the two-dimensional echocardiographic measurements and the surgical measurements. In the last 5 consecutive patients, the echocardiographic measurement was used for the preoperative selection and preparation of the appropriate valve. In conclusion, measurement of the aortic annulus diameter by two-dimensional echocardiography is feasible and clinically useful for the preoperative selection and preparation of homograft aortic valves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934447 TI - Long-term results of aortic valve replacement with nonviable homografts. AB - Between 1965 and 1972, 250 patients (186 men and 64 women; median age, 48 years) underwent aortic valve replacement with homografts preserved with beta propiolactone (98 patients) or irradiation (152 patients); operative mortality was 6% (15 patients). Follow-up to death, reoperation, or recent evaluation was completed in 95% of patients, and median follow-up time was 11.4 years. Thromboembolic events occurred in two patients (0.21 events/100 patients/yr). Risk of reoperation was 22% at 5 years, 62% at 10 years, 85% at 15 years, and 95% at 20 years. Factors associated with increased risk of reoperation were young age, male sex, native aortic valve insufficiency, previous aortic valve surgery, history of endocarditis, and larger homograft size. Survival at 5, 10, 15, and 20 years was 85%, 66%, 53%, and 38%, respectively. Late survival was diminished in older patients and those with native aortic valve insufficiency and coronary artery disease. Aortic valve replacement with nonviable homografts has a high risk of late tissue degeneration and need for reoperation. However, the incidence of thromboemboli is minimal, and grafts can be replaced with low risk (4.5%) so that overall patient survival is similar to that observed with other bioprosthetic or mechanical heart valves. PMID- 1934448 TI - Aortic valve replacement with pulmonary or aortic allografts. AB - Limited availability of aortic valve allografts suggests consideration of pulmonary valve allografts for aortic valve replacement (AVR). From 1987 through 1990, 20 patients underwent AVR with cryopreserved aortic allografts (group 1). Five patients underwent AVR with pulmonary allografts (group 2) because no aortic allografts of the appropriate size were available. Indications for AVR in group 1 were endocarditis in five patients, aortic insufficiency in six, and aortic stenosis in nine. Indications for AVR in group 2 were endocarditis in two patients and aortic insufficiency in three. In group 1 there was one operative death and two late deaths resulting from noncardiac causes. There were no operative or late deaths in group 2. Follow-up was complete (group 1: 1-32 months [mean, 14 months]; group 2: 1-24 months [mean, 13 months]). All surviving patients remain in New York Heart Association (NYHA) class I or II. Postoperative catheterization was performed in 21 of 24 surviving patients. All patients have been followed since hospitalization with serial studies that included computerized cine tomography of the chest and echocardiograms. No false aneurysms, stenoses, or clinically significant regurgitation have occurred, although one patient in group 2 showed 2+ insufficiency at catheterization. One group 1 patient required repeat AVR for recurrent endocarditis. There were no reoperations in group 2. Although longer-term follow-up with larger numbers of patients is necessary, it seems that operative and early postoperative results for AVR have been similar with aortic and pulmonary valve allografts. In selected patients AVR with pulmonary allografts may be appropriate to consider when properly sized aortic allografts are unavailable. PMID- 1934449 TI - Growth and cell viability of aortic versus pulmonic homografts in the systemic circulation. AB - Growth characteristics and cell viability of aortic and pulmonic valve homografts in the systemic circulation were compared in a growing sheep model. Seven aortic and seven pulmonic cryopreserved homografts were implanted in the descending aortae of recipient female lambs. Of seven sheep per group, three were killed at 8 months, three at 12 months, and one at 15 months. Tissue cultures were obtained on homograft valve and root wall specimens. Male donor cells were identified by chromosome analysis. Preimplant to explant changes in pulmonic homograft external diameters at the valve annulus and sinotubular junction increased significantly more than in aortic roots. The postoperative dimensions of the distal anastomotic diameter and length of the graft increased significantly more in pulmonic than in aortic roots by time of explant. Leaflet calcification and valvular stenosis did not develop in either pulmonic or aortic homografts over the period of observation. Calcification in the root wall was significantly less in pulmonic than aortic homografts. Growth on tissue culture was obtained from over 70% of homograft specimens. Viable donor cells were demonstrated in none and 43% of aortic and pulmonic leaflets, respectively, and 71% and 57% of aortic and pulmonary arterial homograft walls, respectively. In conclusion, both aortic and pulmonic homograft valves provide freedom from calcification and stenosis in this model. Continuing expansion of pulmonic root diameters under systemic pressure might lead to late aneurysm formation. Although host cell repopulation of grafts may be advantageous, the presence of viable donor cells in leaflet tissue does not seem necessary to prevent calcific degeneration. PMID- 1934450 TI - Unresolved questions in breast cancer therapy. PMID- 1934451 TI - Improved laboratory diagnosis of septicemia. PMID- 1934453 TI - Cardiac rhythm and conduction disturbances in patients undergoing mitral valve surgery. AB - The occurrence and course of supraventricular rhythm and atrioventricular conduction disturbances were retrospectively compared in 206 patients with isolated mitral valve disease undergoing either valve replacement or ring annuloplasty (mitral repair) between January 1, 1985 and December 31, 1986. The replacement and repair groups were the same size and had approximately equal numbers of patients in sinus rhythm and atrial fibrillation preoperatively. The type of mitral valve operation did not affect the short-term outcome in terms of cardiac rhythm. For both groups, the incidence of patients crossing from sinus rhythm to atrial fibrillation and vice versa on the pre-discharge electrocardiography was equal, and both groups had a low incidence of clinically significant atrioventricular block. PMID- 1934455 TI - Disorders of platelet function: evaluation and treatment. AB - Platelet function involves adhesion, aggregation, secretion, and elaboration of procoagulant activity. Compromise of any of these functions due to an inherited or acquired defect in primary hemostasis can result in bleeding diatheses. Acquired disorders are related to drugs, systemic disease, or hematologic disease. Although laboratory tests are available to evaluate platelet function, the history is of prime importance in the diagnostic workup. Plasmapheresis, dialysis, transfusion of normal platelets, administration of cryoprecipitate, and administration of corticosteroids are all acceptable treatment protocols in specific situations. The drug of choice for treating mild hemostatic abnormalities due to platelet function defects is desmopressin acetate, which may be administered by several routes, produces few, if any, side effects, and carries no risk of infectious disease transmission. PMID- 1934452 TI - Headache and hypertension in a 15-year-old. PMID- 1934454 TI - Eosinophilia-myalgia syndrome: the Cleveland Clinic experience. AB - Eosinophilia-myalgia syndrome is a recently described clinical syndrome caused by a suspected contaminant of L-tryptophan, an essential amino acid that was manufactured and sold as a nutritional supplement. This study reports the clinical and pathological findings of 22 cases of eosinophilia-myalgia syndrome evaluated at the Cleveland Clinic and includes data for up to 1 year of follow-up (for the epidemic cases). Nineteen of the 22 cases were evaluated and followed prospectively in the time period from November 1989 to November 1990. Two of the 22 represented nonepidemic forms of the syndrome which occurred prior to the 1989 epidemic. During a review of all cases of biopsy-proven diffuse fasciitis with eosinophilia at the Cleveland Clinic since 1978, one of the 22 was retrospectively identified as having an epidemic form of the syndrome, with onset in July 1989. In this study, adverse prognosticating factors in eosinophilia myalgia syndrome included nerve and muscle involvement, fasciitis, and weight loss. Eosinophilia-myalgia syndrome is striking in its severity and diversity, and its features are similar to those of two other unusual illnesses--toxic oil syndrome and diffuse fasciitis with eosinophilia. With the recent purification of the suspected contaminant, it is hoped that further clues to the etiology of this syndrome and similar syndromes will be uncovered. PMID- 1934456 TI - Omeprazole: a new drug for the treatment of acid-peptic diseases. AB - Omeprazole is the first of a new class of gastric antisecretory drugs, proton pump inhibitors. It inhibits the H+,K(+)-adenosinetriphosphatase enzyme of the gastric parietal cell, resulting in potent, long-lasting suppression of basal and stimulated acid secretion. The drug is currently approved for treatment of gastroesophageal reflux disease and Zollinger-Ellison syndrome. In clinical trials, treatment with omeprazole results in rapid healing of duodenal ulcers; it is also effective in treating gastric ulcer disease. It is uniformly well tolerated without significant adverse effects, although animal studies linked profound long-term suppression of gastric acid secretion with the development of gastric carcinoids. Potential future uses include the prophylaxis of ulceration secondary to stress or use of nonsteroidal anti-inflammatory drugs, and the prophylaxis of recurrent peptic ulcer disease. PMID- 1934457 TI - Managing the hypertensive patient: reasonable goals. PMID- 1934459 TI - Therapeutic monitoring of cyclosporine by using pharmacokinetic studies. PMID- 1934458 TI - Treating hypertension to prevent coronary disease. AB - Because most patients with mild to moderate hypertension will not suffer a cardiovascular event due to elevated blood pressure, the presence of other risk factors must be assessed. Many of these are alterable with nondrug therapies, which cost little and carry no risks if applied sensibly. Drug therapies have costs, discomforts, and risks and should be used only for those at high risk or those who fail to respond adequately to nondrug therapies. When drug therapy is necessary, start with low doses and aim for a slow reduction of blood pressure, avoiding hypoperfusion and reducing as many risk factors as possible. Alpha blockers, angiotensin-converting enzyme inhibitors, and calcium-channel blockers may avoid metabolic risks associated with high-dose diuretic and beta-blocker therapy. The establishment of therapeutic goals, individualized assessment of status, and a conservative approach to treatment are the basis for optimal management of patients with hypertension. PMID- 1934460 TI - Optimizing polymerase chain reaction technology for clinical diagnosis. PMID- 1934461 TI - Understanding life as chemistry. PMID- 1934462 TI - Abbreviated kinetic profiles in area-under-the-curve monitoring of cyclosporine therapy. AB - Abbreviated kinetic profiles can reduce the number of phlebotomies and drug assays, and thereby the cost of area-under-the-curve (AUC) monitoring. In the present investigation, we used two independent data sets: group 1, 101 AUC profiles from 77 stable renal-transplant patients, which included a 5-h sample in addition to the usual 0-, 2-, 4-, 6-, 10-, 14-, and 24-h samples; and group 2, 100 profiles from 50 stable renal-transplant patients before and after a change in their daily oral dose of cyclosporine. Group I demonstrated a fair correlation between cyclosporine trough concentrations and the AUC calculated from a complete set of seven concentrations (r2 = 0.820 and 0.758 for the 24- and 0-h samples, respectively). Stepwise multiple linear-regression analysis revealed that the abbreviated set of three time points (2, 6, and 14 h) explained 96% of the variance in AUC values calculated from the full set of seven samples; additional time points increased the accuracy only slightly. For group 2, we examined the difference between the observed and the predicted concentrations by linear extrapolation; the error in the observed AUC value, compared with the predicted value calculated from seven time points (-13.2% to -1.2%), was similar to the error from just three time points (-11.5% to 4.5%). Abbreviated AUC profiles involving three time points used with a model equation seem to provide a reliable alternative to full seven-point profiles. PMID- 1934463 TI - Lactate dehydrogenase, creatine kinase, and their isoenzymes in pleural effusions. AB - Lactate dehydrogenase (LD; EC 1.1.1.27) and creatine kinase (CK; EC 2.7.3.2) are widely distributed cytoplasmic enzymes. LD has five and CK has three isoenzymes distributed in different proportions in various tissues. The amounts of LD and CK and the distribution of isoenzymes in different body fluids are not thoroughly characterized. We have measured the total LD and CK concentrations and their isoenzyme distribution in pleural aspirates and in serum from 22 patients with benign conditions and from 14 patients with malignant effusions. In malignant pleural fluid, the mean total LD was 662 U/L; in benign conditions, it was nearly 5840 U/L with large variations (91-43 400 U/L) according to clinical diagnosis, the highest values being reached in inflammatory lesions. The mean total CK concentration in pleural fluid was close to the serum value in both groups of patients, as was the pleural CK isoenzyme distribution. The LD isoenzyme distribution in pleural effusions differed from that in serum in both groups, with LD-4 and -5 being the main isoenzymes in their pleural fluid specimens (greater than 42% of total LD). The total LD concentration correlated somewhat (r = 0.57) with the total pleural protein content. In conclusion, the pleural LD isoenzyme distribution, both in benign and malignant conditions, differs from that in serum, having shifted towards more anaerobic and embryonic isoenzymes (LD 4 and -5). Moreover, the greater the concentration of pleural total LD, the greater the proportion of LD-4 and -5. These data suggest that visceral or parietal pleural cells are rich in LD isoenzymes 4 and 5. PMID- 1934464 TI - New method for isolating and quantifying intermediate and beta-very-low-density lipoprotein cholesterol. AB - We describe a new method, useful to clinical laboratories, for assessing intermediate density (IDL) or beta-very-low-density (beta-VLDL) lipoprotein cholesterol. The technique involves selective precipitation properties of the qualitative Wieland and Seidel post-electrophoretic method that immobilizes IDL and beta-VLDL in the beta-zone of an agarose slide (Clin Chem 1973;19:1139-41). In our method, we separate low-density lipoprotein (LDL) in a second electrophoretic step, in which LDL moves toward the anode, and then quantify the cholesterol of the above lipoproteins remaining in the precipitate band at the beta-zone. Replicate within-run precision (CV) of 15 aliquots of a sera pool was 10.1%. The correlation with sequential ultracentrifugation of 30 samples was r = 0.96 (P less than 0.001). Serum reference values for 30 normal individuals are 57 +/- 7.0 mg/L. Seven phenotype III hyperlipoproteinemic patients had the highest concentrations of IDL or beta-VLDL cholesterol in serum, 1620 +/- 346 mg/L. PMID- 1934465 TI - Use of immunoglobulin heavy-chain and light-chain measurements in a multicenter trial to investigate monoclonal components: I. Detection. AB - We assessed the combined use of serum protein electrophoresis (SPE) and nephelometric measurement of immunoglobulin heavy- and light-chain components for detecting serum monoclonal immunoglobulins (monoclonal components, MC) in 4788 unselected samples from 4173 patients. MC were detected in 514 samples from 390 patients. In 356 these were detected by SPE; the other 34 had a normal SPE pattern but an abnormal kappa:lambda light-chain ratio (KLR). Only 208 of the 356 (58%) samples with bands by SPE had abnormal KLRs. Samples with MC concentrations greater than 5 g/L had a higher proportion of abnormal KLRs (75%) than those with concentrations less than 5 g/L (42%). The KLR was abnormal in 13% of samples in which no MC were visible by SPE or immunofixation electrophoresis (IFE). Compared with quantitative measurements of immunoglobulin heavy and light chains, high quality SPE remains the method of choice for the detection of MC. Quantitative methods, however, are able to detect additional MC, especially those containing free light chains, and in the absence of SPE and IFE will detect about 75% of MC present at greater than 5 g/L. PMID- 1934466 TI - Use of immunoglobulin heavy-chain and light-chain measurements in a multicenter trial to investigate monoclonal components: II. Classification by use of computer based algorithms. AB - We describe a computer algorithm for classifying serum monoclonal proteins (MC) based on serum protein electrophoresis (SPE) and the automated measurement of kappa and lambda light chains and IgG, IgA, and IgM. We developed the algorithm by using a large database of unselected samples containing MC collected in a multicenter study. The performance of the algorithm was optimized by using iterative computational procedures and was tested on both the development database and on an independent set of MC-containing samples. With the development database, the algorithm correctly classified 50% and misassigned 2.5% of the MC. Where the MC were present in concentrations greater than 10 g/L, the rate of successful classification increased to 72% with 3% misclassification. When the algorithm was tested on a group of 101 MC-containing samples from an independent source, 67% were correctly classified and 8% misclassified, half of the latter being unusual IgD myelomas. We discuss the scope for the application of the algorithm in routine laboratory practice involving personal computer software. PMID- 1934467 TI - Importance of creatinine analyses of urine when screening for abused drugs. AB - We report here a simple method involving urine creatine measurements for testing authenticity and reducing false-negative results in urine testing for drugs of abuse. Urinary creatinine in consecutive patient samples (n = 176) ranged between 0.1 and 31.9 mmol/L (mean 9.8 +/- SD 6.2) and the osmolality in these urines ranged between 49 and 1183 mOsm/kg (mean 595 +/- SD 276). With other consecutive samples in which creatinine was (arbitrarily chosen) less than 4.3 mmol/L (n = 85), the correlation with osmolality was lower. In 10 randomly selected urine samples from different patients, all "clean" for all drugs of abuse in initial immunological drug testing with approved methodology (in which creatinine was less than 4.3 mmol/L and osmolality was less than 200 mOsm/kg), five patients turned out to be drug positive after a simple concentration by volume. In a formerly heavy smoker of cannabis, the excretion of cannabinoids and creatinine was monitored for 93 days. The substances showed very good correlation throughout this period (r = 0.93, P less than 0.001), whereas simple measurements of cannabinoid concentrations would have falsely indicated several relapses of cannabis abuse. Urine samples used in drug-abuse testing should be tested for creatinine; if creatinine is less than 4.0 mmol/L, negative results for drugs may not be valid. PMID- 1934468 TI - Biological variability of superoxide dismutase, glutathione peroxidase, and catalase in blood. AB - We studied the biological variability of blood superoxide dismutase (SOD; EC 1.15.1.1), glutathione peroxidase (GPX; EC 1.11.1.9), and catalase (CAT; EC 1.11.1.6) in a sample of 1836 apparently health subjects, ages 4-97 years. SOD and GPX activities were assayed in plasma (P) and erythrocytes (E) by automated methods, and CAT was measured in erythrocytes by a manual technique. No statistically significant variation of these antioxidant enzyme activities according to gender was demonstrated, except for E-GPX, which was slightly but significantly higher in women than in men (P less than 0.001). Activities appear rather stable in adults less than 65 years old, but decrease for most enzymes in the elderly. There is no evidence that weight, blood pressure, or menopause influences the antioxidant enzymes' activities. In girls ages 10-14 years, E-SOD activity is reduced by 16% (P less than 0.05) after menarche. Variations related to smoking and alcohol consumption are slight and concern only P-SOD and P-GPX, respectively. Conversely, intake of some drugs (e.g., anti-inflammatory agents, antidepressants, and thyroid hormones) modifies activity of some of the three enzymes. E-SOD positively correlates with P-SOD (r = 0.216, P less than 0.001) and E-CAT (r = 0.123, P less than 0.001), and E-GPX with P-GPX (r = 0.218, P less than 0.001). Finally, we propose reference intervals for activities of the three antioxidant enzymes in blood in individuals less than 65 years old. PMID- 1934469 TI - Cholesterol operational process specifications for assuring the quality required by CLIA proficiency testing. AB - Current U.S. governmental regulations and requirements for the quality of laboratory tests do not provide a consistent form, comparable numbers, or practical specifications for the routine operation of laboratory testing processes. For cholesterol, as an example, the Health Care Financing Administration provides an analytical performance criterion for proficiency testing to enforce the Clinical Laboratory Improvement Act (CLIA), whereas the U.S. National Cholesterol Education Program (NCEP) provides clinical guidelines for test interpretation, as well as analytical goals for imprecision and inaccuracy. Routine operating process specifications for imprecision, inaccuracy, and quality control can be derived from the analytical and clinical requirements for quality. Use of an analytical "total error" model and a clinical "decision interval" model provides logically consistent and numerically comparable specifications. Studies with these coherent models indicate that a cholesterol testing process properly planned to satisfy the CLIA analytical requirement will also satisfy the NCEP clinical requirement. To provide 90% assurance of detecting systematic shifts of a magnitude that would cause the CLIA analytical requirement to be exceeded, the operational specifications for a cholesterol testing process are an allowable CV of less than or equal to 2%, an allowable bias of less than or equal to 1%, and a control procedure with two measurements per run interpreted by 1(3)s, 1(2.5)s, or 1(3)s/2(2)s/R4s control rules. PMID- 1934470 TI - Multianalyte microspot immunoassay--microanalytical "compact disk" of the future. AB - Throughout the 1970s, controversy centered both on immunoassay "sensitivity" per se and on the relative sensitivities of labeled antibody (Ab) and labeled analyte methods. Our theoretical studies revealed that RIA sensitivities could be surpassed only by the use of very high-specificity nonisotopic labels in "noncompetitive" designs, preferably with monoclonal antibodies. The time resolved fluorescence methodology known as DELFIA--developed in collaboration with LKB/Wallac--represented the first commercial "ultrasensitive" nonisotopic technique based on these theoretical insights, the same concepts being subsequently adopted in comparable methodologies relying on the use of chemiluminescent and enzyme labels. However, high-specific-activity labels also permit the development of "multianalyte" immunoassay systems combining ultrasensitivity with the simultaneous measurement of tens, hundreds, or thousands of analytes in a small biological sample. This possibility relies on simple, albeit hitherto-unexploited, physicochemical concepts. The first is that all immunoassays rely on the measurement of Ab occupancy by analyte. The second is that, provided the Ab concentration used is "vanishingly small," fractional Ab occupancy is independent of both Ab concentration and sample volume. This leads to the notion of "ratiometric" immunoassay, involving measurement of the ratio of signals (e.g., fluorescent signals) emitted by two labeled Abs, the first (a "sensor" Ab) deposited as a microspot on a solid support, the second (a "developing" Ab) directed against either occupied or unoccupied binding sites of the sensor Ab. Our preliminary studies of this approach have relied on a dual channel scanning-laser confocal microscope, permitting microspots of area 100 microns 2 or less to be analyzed, and implying that an array of 10(6) Ab containing microspots, each directed against a different analyte, could, in principle, be accommodated on an area of 1 cm2. Although measurement of such analyte numbers is unlikely ever to be required, the ability to analyze biological fluids for a wide spectrum of analystes is likely to transform immunodiagnostics in the next decade. PMID- 1934471 TI - CA-125 concentrations in malignant and nonmalignant disease. AB - CA-125 is a high-molecular-mass glycoprotein expressed on the cell surface of some derivatives of embryonic coelomic epithelium. This tumor-associated antigen widely used to monitor ovarian carcinomas has been suggested as a promising noninvasive test that could differentiate benign from malignant conditions. Based on results of various studies, CA-125 measurement appears to be very useful in monitoring the response to therapy of ovarian carcinoma and for detecting tumor recurrence as exemplified in Case 1. However, because of the high frequency of false-positive results associated with many benign conditions, CA-125 is of little value as a screening test for ovarian carcinoma. A brief list of the most common benign conditions associated with CA-125 increase includes menstruation, pregnancy, benign pelvic tumors, pelvic inflammatory diseases, ovarian hyperstimulation syndrome, peritonitis, and many diseases leading to pleural effusion or ascites. According to several studies, a marked increase in CA-125 of greater than 1000 units/mL, as seen in Case 2, and even up to 5000 units/mL, could be seen in some benign conditions. This finding further limits the value of CA-125 as a potential noninvasive procedure to differentiate benign from malignant diseases. Although values up to 10,000 units/mL are occasionally seen in patients with ovarian carcinoma, we are reluctant to state that any concentration of CA-125 can be clearly diagnostic of malignancy. PMID- 1934472 TI - Efficient extraction of basic, neutral, and weakly acidic drugs from plasma for analysis by gas chromatography-mass spectrometry. AB - We describe a method for efficiently extracting basic, neutral, and weakly acidic drugs from plasma for toxicological analysis by gas chromatography-mass spectrometry (GC/MS). The 2-mL plasma sample is diluted with an equal volume of saturated NaCl containing triethylamine, 10 mmol/L, and then extracted twice with 4 mL of an equivolume solution of dichloromethane/acetone. The organic (top) phases are combined, then mixed with 1 mL of water, 200 mg of NaHCO3, and 100 microliters of acetic anhydride. This mixture is then heated at 75 degrees C until the solvents have boiled off and aqueous acetylation is complete (less than 30 min). After addition of 1 mL of water and 2 g of NaCl, the sample is extracted twice with 2 mL of dichloromethane/acetone (2/1 by vol). The combined extracts are dried and then subjected to thin-layer chromatography on a blank Toxi-Lab Toxi-A chromatogram with 1-chlorobutane as the developing solvent (about 6 min). After the lipids have migrated with the mobile phase, the drugs are eluted from the origin with acetone/triethylamine (29/1 by vol), evaporated, and reconstituted in injection solvent. With this procedure drugs are recovered relatively quickly (less than 2 h) and the GC/MS total ion chromatograms are very clean. Studies with 13 basic, neutral, and weakly acidic drugs showed that all except theophylline were extracted with recoveries of at least 75%. PMID- 1934473 TI - Lactate analyzer with continuous blood sampling for monitoring blood lactate during physical exercise. AB - To monitor changes in the concentration of blood lactate during physical exercise, we used an automated lactate analyzer based on an electro-enzymatic method with continuous blood sampling through a catheter. The lactate concentration was measured every 2 min; between measurements, the instrument was calibrated with a lactate standard. Ascorbic acid, bilirubin, hemoglobin, creatinine, uric acid, and glucose did not interfere with the measurements. The lactate concentrations in blood samples from apparently healthy subjects before and after exercise correlated well (r = 0.993) with results by the conventional enzymatic method. We measured the blood lactate concentrations in nine apparently healthy volunteers during exercise on a treadmill with an increasing workload. The point at which lactate concentrations started to increase was detected easily. Thus, the lactate analyzer is suitable for monitoring changes in blood lactate concentrations during exercise. PMID- 1934474 TI - Rapid, semi-quantitative assay of C-reactive protein evaluated. AB - We evaluated a new rapid semi-quantitative immunometric assay of C-reactive protein (CRP) as a screening test for sepsis by comparison with an automated nephelometric method. Plasma samples (n = 101) from preterm infants during the first week of life were saved for CRP analyses. We measured CRP by the Nycocard semiquantitative method and compared the results with those obtained with a Behring Nephelometer. A CRP value less than 10 mg/L was considered to be negative for infection. All CRP results read as less than 10 mg/L (negative) by the Nycocard method were also less than 10 mg/L by the comparison method, and all CRP values found to be greater than 20 mg/L (positive) by the Nycocard method were also positive by the comparison method. Results in the 10-20 mg/L range were considered equivocal. We conclude that the Nycocard CRP semi-quantitative method is a rapid and useful screening test for sepsis in preterm infants. PMID- 1934475 TI - Rapid diagnosis of familial defective apolipoprotein B-100 by Amplification Refractory Mutation System. AB - We report a method for the diagnosis of familial defective apolipoprotein (apo) B 100, using the Amplification Refractory Mutation System (ARMS) and either whole blood or extracted DNA in the polymerase chain reaction. Normal and mutant alleles are identified by using two allele-specific oligonucleotide primers, each with the same common primer, to amplify a 187-bp fragment of the apo B-100 gene. Fragment amplification occurs only when the allele-specific primer matches the nucleotide sequence of the template DNA. The amplification product is detected by agarose gel electrophoresis, followed by staining with ethidium bromide. The technique is simple, reliable, and robust. It avoids the use of radiation or hybridization with allele-specific oligonucleotide probes, and is well suited for use in the routine clinical chemistry department. PMID- 1934476 TI - Chemiluminescence immunoassay of aldosterone in serum. AB - A chemiluminescence immunoassay (CLI) for the direct measurement of aldosterone in serum was developed with aminobutylethyl isoluminol (ABEI) as the label. In this competitive assay the samples are incubated with sample, antibody, aldosterone-carboxymethyl oxime-ABEI, and paramagnetic particles coated with second antibody. After magnetic separation and washing, the samples are incubated with 200 microL of NaOH (2 mol/L) at 60 degrees C for 30 min. In the luminometer the chemiluminescence is produced by the serial injection of 150 microL each of microperoxidase and H2O2 solutions. Comparison of results with an RIA method showed excellent agreement: CLI = 1.001 RIA + 0.020 (r = 0.99, n = 93). The method is simple and avoids the hazards and costs associated with isotopic waste. The label has a shelf life of at least two years. PMID- 1934477 TI - High-performance liquid-chromatographic method compared with a modified radioimmunoassay of cotinine in plasma. AB - Cotinine is a sensitive and specific biochemical marker of exposure to cigarette smoke. We describe a simple solid-phase extraction of cotinine from plasma before quantification by HPLC. Extraction recovery was 97.9% +/- 11.0% for plasma concentrations of 5-400 micrograms/L. Baseline separation of cotinine and caffeine was achieved within 11 min of injection onto a C18 reversed-phase column. The mobile phase was citric acid/dibasic potassium phosphate (30 mmol/L each, pH 6.0) containing 100 mL of acetonitrile per liter. Within-day and day-to day precision (CV) were 4.7% and 8.4%, respectively. We also describe a modification of the Nicotine Metabolite RIA kit (Diagnostic Products Corp.) for quantifying cotinine in plasma. Recovery of cotinine from supplemented plasma was within 10% of the expected value with this RIA kit. Interassay precision averaged 8.1% for samples in the range 50-400 micrograms/L; intra-assay precision averaged 3.6% at 230 micrograms/L and 8.7% at 53 micrograms/L. Correlation between the two methods was RIA = 1.13 HPLC + 14.8 (n = 128, r = 0.957, P less than 0.001). Both methods are technically simple to perform. PMID- 1934478 TI - Determination of intact parathyrin by immunoradiometric assay evaluated in normal children and in patients with various disorders of calcium metabolism. AB - We report the reference values for intact parathyrin (PTH) measured by a two-site immunoradiometric assay (IRMA) during childhood. The study has been carried out in 215 healthy children and adolescents, ages 2.0 to 18.7 years. Some patients with altered mineral homeostasis were also studied to assess the sensitivity of the method in a clinical setting. Mean intact PTH concentrations were 30.8 (SD 9.6) ng/L; the median was 28.5 ng/L. Normal reference values were 16.0-59.0 ng/L (95% confidence interval). The distribution of intact PTH values was nongaussian. We found no significant variations between males and females and no age-related variations. The IRMA used was sufficiently sensitive to detect differences in PTH concentrations between healthy children and patients with hypocalcemia or hypercalcemia. PMID- 1934479 TI - American Thyroid Association assessment of current free thyroid hormone and thyrotropin measurements and guidelines for future clinical assays. The Committee on Nomenclature of the American Thyroid Association. PMID- 1934480 TI - Cross-reactivity of a vancomycin degradation product in three immunoassays of vancomycin. PMID- 1934481 TI - Ultrafiltration of serum to eliminate bilirubin interference in the kinetic Jaffe determination of creatinine. PMID- 1934482 TI - Effect of diluent volume on determinations of enzyme activities with the Cobas Bio analyzer. PMID- 1934484 TI - Possible explanation for decrease in albumin content during storage of urine samples. PMID- 1934483 TI - Significant differences between arterial and venous endothelin-like immunoreactivity in human plasma. PMID- 1934485 TI - Modified analysis for C1q as protein-bound hydroxyproline in the euglobulin fraction of serum. PMID- 1934486 TI - Serum index identifies lipemic samples causing interference with bilirubin assay on Hitachi 717. PMID- 1934487 TI - Cyclosporine monoclonal immunoassays: fluorescence polarization immunoassay vs RIA. PMID- 1934488 TI - Synthetic sweetener cyclamate as a potential source of false-positive amphetamine results in the TDx system. PMID- 1934489 TI - Elimination of glucose interference in enzymatic determination of inulin. PMID- 1934490 TI - Increase in CA-125 concentrations in children. PMID- 1934491 TI - Contamination of breath methane samples in sterilized Vacutainer Tubes. PMID- 1934493 TI - Serum fructosamine and obesity. PMID- 1934492 TI - Two specific immunoassays of cyclosporine compared in liver transplant recipients. PMID- 1934494 TI - Adenosine deaminase increased in serum in toxoplasmosis. PMID- 1934495 TI - Simple, quantitative enzymic assay of galactose in urine. PMID- 1934496 TI - Elevated serum bile acids in hepatic vein occlusion and idiopathic portal hypertension. PMID- 1934497 TI - The effective inhibition of the Maillard reaction by guanabenz acetate, and its relevance to the prevention of diabetic complications. PMID- 1934498 TI - Screening for disorders of pyruvate metabolism by measuring the ratio of the rates of lactate production and pyruvate decarboxylation in cultured skin fibroblasts. AB - We assayed the rates of lactate production from [1-14C]pyruvate and decarboxylation of [1-14C]pyruvate in cultured skin fibroblasts from 8 patients with disorders of pyruvate metabolism and 16 control subjects. The disorders of pyruvate metabolism could be more readily detected by measuring the ratio between the rates of lactate production and pyruvate decarboxylation by cultured skin fibroblasts than by measuring either the rate in isolation. PMID- 1934499 TI - Determination of alpha-amylase using a new blocked substrate (3-ketobutylidene beta-2-chloro-4-nitrophenyl-maltopentaoside). AB - A new substrate, 3-ketobutylidene beta-2-chloro-4-nitrophenylmaltopentaoside (3KB CNPG5), was used for the determination of alpha-amylase (EC 3.2.1.1) in serum and urine. Under this alpha-amylase assay condition, 3KB-CNPG5 is resistant to glucoamylase and alpha-glucosidase, which are auxiliary enzymes, because the 4- and 6-positions of the non-reducing-end glucose residue are modified by the 3 ketobutylidene group. The assay using 3KB-CNPG5 for alpha-amylase activity is a highly sensitive method that uses 2-chloro-4-nitrophenol (CNP) as an aglycone, and is a stable method for determination of alpha-amylase activity in biological fluids. PMID- 1934500 TI - High-performance liquid chromatographic determination of urinary cysteine and cystine. AB - A method for quantitative determination of cystine and its monomer, cysteine, is presented using reversed phase HPLC with precolumn derivatization by ophthaldialdehyde (OPA). The new application exhibits a two step procedure for overcoming the minimal fluorescence of the OPA-derivatives of cysteine and cystine: after reduction of cystine to cysteine by dithiothreitol the sulfhydryl group of cysteine is blocked with iodoacetic acid. Optimum reaction conditions of this derivatization procedure are described. Special precautions relating to the rather fast oxidation of cysteine are necessary. Collecting urine directly into sulphosalicylic acid prevents oxidation of cysteine up to 5 days. Initial results of urinary concentration of cysteine and cystine of healthy control persons and patients suffering from cystinuria are presented. PMID- 1934501 TI - Clinical evaluation of high-performance affinity chromatography for the separation of bone and liver alkaline phosphatase isoenzymes. AB - The newly described high-performance (HPLC) affinity chromatography method for the separation of human bone and liver alkaline phosphatase (ALP, EC 3.1.3.1) isoenzymes was clinically evaluated. The improved resolution of bone from liver isoenzyme and lower detection limit was achieved by conjugation of wheat-germ lectin (WGL) to a diol-bonded silica gel column, stepwise elution with N acetylglucosamine (NAG) and post column derivatization using para-nitrophenyl phosphate substrate. To establish a reference interval, we measured bone ALP in 86 healthy women, ages 33 to 95 years. The normal reference interval is described by a piecewise linear regression on age (R2 = 0.20, P less than 0.01). For women less than or equal to 45 years, bone ALP, U/l = 8.495. For normal women between ages of 45 to 55 years, bone ALP, U/l = -12.765 + 0.472* age. If age greater than or equal to 55 years, then bone ALP, U/l 13.219. In all 10 patients with primary biliary cirrhosis, serum bone ALP levels were elevated. In addition, sera from 43 patients with diverse metabolic bone diseases were evaluated. As expected, the sera from all 6 patients with Paget's disease and 2 with osteolytic metastasis had bone ALP activity which was greater than 3 standard deviations (SD) from the mean. In all 10 patients with hypoparathyroidism, bone ALP levels were depressed. Only 1 of the 9 patients with glucocorticoid excess and 2 of the 7 patients with primary hyperparathyroidism had elevated bone ALP when compared to the 95% confidence interval for the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934502 TI - Serum fructosamine/haemoglobin A1 ratio predicts the future changes in haemoglobin A1 in type 2 (non-insulin dependent) diabetic patients. AB - The aim of the study was to define clinical interpretation of the parallel measurements of serum fructosamine and HbA1 in diabetic patients. We studied 14 type 2 diabetic patients over a 16-wk period. The cross-sectional analysis showed no correlation between serum fructosamine and HbA1 concentrations during the period of changing glycaemic control. The correlations, however, became significant (P less than 0.05) at 12 (r = 0.60) and 16 (r = 0.87) weeks, i.e. after glycaemia had stabilised. Longitudinal analysis of individual patients' data over the 16-wk period showed a significant correlation between serum fructosamine and HbA1 (r = 0.55 to r = 0.94) which was present in 8 out of 14 patients. The changes in fructosamine concentration preceded those observed in HbA1. The ratio of fructosamine/HbA1 predicted the changes in HbA1 over the following month (r = 0.54, P less than 0.001). Thus, we demonstrated that the parallel measurement of fructosamine and HbA1 provides information on future trends in HbA1 concentration in diabetic patients. PMID- 1934503 TI - Determination of membrane cholesterol in normal and pathological red blood cells. PMID- 1934504 TI - Stable isotope dilution assay for 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25 tetrol and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,23,25-pentol in human serum using [26,27-D6] labeled internal standards; a highly accurate approach to the serological diagnosis of cerebrotendinous xanthomatosis. PMID- 1934505 TI - Simultaneous analysis of plasma phenethylamine, phenylethanolamine, tyramine and octopamine in patients with hepatic encephalopathy. PMID- 1934506 TI - Atherogenic risk factors in cerebrotendinous xanthomatosis. AB - In a study of coronary artery disease in patients with cerebrotendinous xanthomatosis (CTX), we documented the presence or absence of atherogenic risk factors and performed detailed analyses of serum lipid and lipoprotein profiles. Four of the seven patients examined had coronary arterial narrowing and/or obstruction, but multiple atherogenic risk factors were not found in any of these patients. Total cholesterol (T.ch) levels and low density lipoprotein-cholesterol (LDL-ch) levels were lower, and high density lipoprotein2-cholesterol (HDL2-ch) levels were higher in CTX patients than in controls. Triglyceride and very low density lipoprotein (VLDL) levels were significantly lower in the former. Indices correlating with the risk of atherosclerosis, such as the atherogenic index, and the ratios of apolipoprotein B/apolipoprotein AI, HDL2-ch/LDL-ch, HDL2-ch/HDL3 ch, indicated that CTX serum was, in fact, 'anti-atherogenic'. However, coronary artery disease is frequently seen in patients with CTX. This discrepancy suggests the existence of a unique mechanism by which atherosclerosis is induced in patients with CTX. We discuss a mechanism of disturbed lipoprotein metabolism which might be responsible for the deposition of sterols in the tissues of patients with CTX. PMID- 1934508 TI - Serum release of the creatine kinase tissue-specific isoforms MM3 and MB2 is simultaneous during myocardial reperfusion. AB - The release sequence of the creatine kinase MM and MB tissue-specific subforms after myocardial reperfusion was elucidated by computer-fitting serial enzyme data from 6 humans in whom coronary flow in the infarct-related artery was angiographically documented as initially zero, opening to normal after angioplasty. The model equation used demonstrated acceptable performance according to standard criteria including visual examination and statistical parameters. The model successfully described the sequential conversion of the MM3 and MB2 tissue isoforms to their respective MM2 and MM1, and MB1 isoforms. Release of MM3 and MB2 was simultaneous, differing in calculated release times by 0.2 to 10%, median 3%. Since MB2 release is not retarded after myocardial reperfusion compared to the more clinically established CK-MM3 isoform, assays for sensitive and rapid measurement of MB2 should be the focus for the non invasive assessment of myocardial reperfusion due to its higher cardiospecificity. PMID- 1934507 TI - Measurement of plasma free steroids by direct radioimmunoassay of ultrafiltrate in association with the monitoring of free components with [14C]glucose. AB - We describe a modified method of centrifugal ultrafiltration using the Grace MPS 3 device for the measurement of plasma free (unbound) steroids (cortisol, testosterone, estradiol, and prednisolone). Plasma was incubated with [14C]glucose to monitor the movement of free components, applied to the MPS-3 and centrifuged. Steroid concentration of ultrafiltrate was directly measured by radioimmunoassay, and multiplied by the ratio of [14C]glucose count (dpm) in plasma to [14C]glucose count (dpm) in ultrafiltrate. The data by this method correlated well with those obtained by equilibrium dialysis. Our results of free steroid in healthy volunteers and patients with various diseases were comparable with the previously reported values. This procedure showed the advantages of small sample volume, rapid separation and the ability to process a large number of samples in a single run. PMID- 1934509 TI - A new sensitive method for determining endotoxin in whole blood. AB - We developed a microplate method for determining endotoxin in whole blood with Endospecy, an endotoxin-specific chromogenic limulus test reagent. The factors in blood that would interfere with the test were successfully removed by exposing samples to 0.66 mol/l HNO3 containing 0.25% Triton X-100. Recoveries of various endotoxins spiked into whole blood of humans and experimental animals were almost complete, and were not enhanced by sample dilution. Normal endotoxin concentration in human whole blood was less than 10 pg/ml in reference to Escherichia coli 0111:B4 endotoxin. Measurements on paired whole blood and platelet-rich plasma (PRP) samples from 50 normal and 132 diseased subjects showed a good correlation (r = 0.901, P less than 0.01). This microplate whole blood method has advantages over the conventional PRP method in that it requires less time, less amount of sample and limulus reagent, and less risk of contamination during the procedure. PMID- 1934510 TI - A new mutant erythrocyte pyrimidine 5'-nucleotidase characterized by fast electrophoretic mobility in a Chinese boy with chronic hemolytic anemia. PMID- 1934511 TI - A universal eluent system for free amino acid analysis in biological fluids. PMID- 1934512 TI - Macro creatine kinase type 2 in a patient with prostatic carcinoma. PMID- 1934514 TI - Suppression/stimulation of chemiluminescence by human seminal plasma. PMID- 1934513 TI - Measurement of total fasting-state serum bile acids: comparison of a solid-phase bioluminescence enzymatic assay, a homogeneous fluorescence enzymatic assay and isotope dilution gas chromatography-mass spectrometry. PMID- 1934515 TI - Re: EEG in coma. PMID- 1934516 TI - Short and long latency auditory evoked potentials in traumatic brain injury patients. AB - Short latency auditory nerve and brainstem evoked responses (BAERs) and long latency cortical auditory evoked responses (CAERs) in 75 long-term traumatic brain injury (TBI) cases were compared. CAERs were found to be significantly correlated with clinical disability as measured by the Disability Rating Scale, while BAERs were not. Also, BAER patterns were consistently and significantly less abnormal and less sensitive to overall dysfunction than CAER patterns. Findings support previous observations that BAERs have relatively little utility for evaluating in surviving TBI patients the degree of overall brain impairment. In general, long latency AEP patterns are better able to reflect the extent and severity of brain dysfunction and overall clinical condition than are short latency AEP patterns in long-term severe TBI patients, and these patterns should be obtained routinely in the evaluation of such patients. PMID- 1934517 TI - Neurodiagnostic testing in patients with closed head injury. AB - This brief review summarizes the current understanding of mild closed head injury with postconcussion syndrome. It is to be emphasized that objective evaluation be performed because it is critical to the assessment of the patient. Increased awareness of patients with symptoms in association with heightened sensitivity and caring will go a long way in helping the millions of patients yearly with mild to moderate head injury. Only with objective scientific data will the understanding of the causes of the varied symptomatology of the postconcussion syndrome be thoroughly understood. PMID- 1934519 TI - Longitudinal quantitative EEG findings after acute carbon monoxide exposure: two case studies. PMID- 1934518 TI - Possible relationship of periodic lateralized epileptiform discharges to thalamic stroke. AB - A patient with a unilateral thalamic infarct and associated periodic lateralized epileptiform discharges is described. The implications of this for the pathophysiology of PLEDs is discussed. PMID- 1934520 TI - Physiological classification of sleep-wake states: based on tri-vesicular (3V) model of the brain. AB - A new physiological classification of sleep-wake states, based on a novel Tri Vesicular (3V) model of the brain is proposed. The 3V model consists of an interconnected network of three primal brain vesicles, namely, right and left Arch-Encephalon (Mesencephalon + Diencephalon + Telencephalon) and one DeuterEncephalon (Metencephalon + Myelencephalon). Nine sleep-wake states are defined on the basis of the central activational index (activation and/or inhibition of the 3 brain vesicles), and the level of global arousal. Four sleep states I-IV, four wake states I-IV, and one transitional sleep-wake state, are characterized. The four sleep states correspond with the four non-REM sleep stages, the transitional sleep-wake state correlates with REM sleep, and four wake states are defined in terms of minimal, low, moderate, and high, global behavioral arousal. Three sets of data in the form of polysomnographic and aerobic exercise studies in five adult subjects, and 30 days' data of self monitored arousal and oro-nasal breathing patterns, are provided in support of this physiological classification of sleep-wake states and the 3V brain model. PMID- 1934521 TI - Dermatomal somatosensory evoked potentials in brachial plexus injuries. AB - The dermatomally stimulated somatosensory evoked potential is an essentially painless, noninvasive procedure that can add useful information to the diagnosis of the site and extent of brachial plexus injuries. In this study, 13 patients with unilateral brachial plexus injuries who had previously undergone conventional electromyographic testing underwent somatosensory evoked potential recording with median, ulnar, radial, musculocutaneous nerve and C5, C6, C7, C8 and T1 dermatomal stimulation. There was no significant difference in the peak latencies, interpeak latencies, or amplitudes of the major peaks between the normal values and the values from the affected levels. However, analysis for absence or presence of major peaks from side-to-side was useful in supporting the data from electromyographic and radiologic studies, as well as in providing more specific information as to the level of injury and extent of injury in two of the cases. The accurate diagnosis can provide the information needed to determine patient treatment as well as plan the rehabilitation program of the patient. The dermatomal somatosensory evoked potential can be a useful supplement to the assessment of the patient with a brachial plexus injury. PMID- 1934522 TI - Computerized EEG frequency analysis in Gilles de la Tourette syndrome. AB - EEG abnormality has been reported in Gilles de la Tourette Syndrome but not confirmed in later studies. We carried out computerized EEG frequency analysis in 30 patients with the disorder, using Nicolet Pathfinder II frequency analysis software, versions 1.2 and 3.1 EEG was recorded from 01-A1+A2, 02-A1+A2, Fz A1+A2, F7-C3, F8-C4, T5-01, and T6-02 in Tourette Syndrome patients and controls. Controls were taking no medications, and drug therapy for Tourette Syndrome had been stopped or not yet initiated in the patient group. Modal alpha frequency (MAF), maximal alpha frequency (MxAF), and spectral edge frequency (SEF) was measured in occipital and frontal derivations in 24 patients and controls. Left frontal (MOLF) and right frontal (MORF) mobility was calculated in F7-C3 and F8 C4 in 21 patients and controls. No significant differences were found between Tourette Syndrome patients and controls by two-tailed t-test. These findings are in accord with recent evidence of little or no EEG abnormality in Tourette Syndrome patients as compared to normals. PMID- 1934523 TI - Cytokines and endocrine function: an interaction between the immune and neuroendocrine systems. PMID- 1934524 TI - Ovarian response to gonadotrophins: effects of growth hormone. PMID- 1934525 TI - Ovarian sensitization to gonadotrophins by human growth hormone. Persistence of the effect beyond the treated cycle. AB - OBJECTIVE: To document the persistence of a sensitizing effect of human growth hormone on the ovarian responsiveness to human menopausal gonadotrophin in anovulatory patients resistant to standard gonadotrophin doses. DESIGN: We performed an open study of three patients given 4, 12 or 24 IU recombinant growth hormone on alternate days for 5-7 doses, concomitantly with gonadotrophin, and assessed gonadotrophin dose requirements before, during and after the cycle of growth hormone therapy. PATIENTS: We studied two with isolated gonadotrophin deficiency and primary amenorrhoea and one with a pituitary tumour and hyperprolactinaemia which normalized with bromocriptine but in whom there was persisting secondary amenorrhoea. MEASUREMENTS: We measured body mass index, FSH, LH, prolactin, growth hormone, insulin-like growth factor I (IGF-I), oestradiol and inhibin at baseline and growth hormone, IGF-I, oestradiol and inhibin during treatment. In addition we noted the numbers of ampoules (75 IU) and the last pre hCG dose of gonadotrophin used before, during and after growth hormone therapy. RESULTS: Baseline growth hormone levels were low but IGF-I levels were normal. IGF-I increased by 20% in the subject given 4 IU growth hormone, and by 50-100% in the other two. Pretreatment daily gonadotrophin dosage of 8-11 ampoules pre hCG was reduced to 3-6 ampoules during growth hormone and 3-4 post growth hormone. This effect persisted for 4 cycles over 7 months in one subject. CONCLUSION: Growth hormone causes persisting ovarian sensitization to gonadotrophin and may produce a substantial lowering of gonadotrophin requirement for ovulation induction in patients with large dosage needs. PMID- 1934526 TI - TRIAC (3,5,3'-triiodothyroacetic acid) has parallel effects at the pituitary and peripheral tissue levels in thyroid cancer patients treated with L-thyroxine. AB - OBJECTIVE: To investigate whether the addition of 3,5,3'-triiodothyroacetic acid (TRIAC) to thyroxine (T4) treatment can suppress TSH secretion without inducing thyrotoxicosis at the periphery. DESIGN: Thyroid cancer patients were studied with different treatment modalities: T4 at supraphysiologic dose (2.5 +/- 0.3 micrograms/kg/day) and after reduction to a physiologic dose (1.8 +/- 0.3 micrograms/kg/day); then with the addition of TRIAC 500 or 1000 micrograms/day to the physiologic T4 treatment dose. PATIENTS: Twenty-two patients who had total thyroid ablation for differentiated thyroid carcinoma. MEASUREMENTS: Clinical and biological parameters of thyroid hormone action studied included heart rate, serum creatine phosphokinase, testosterone-oestradiol binding globulin, procollagen III and osteocalcin levels. RESULTS: The addition of TRIAC induced a significant and dose-dependent decrease in serum TSH levels and parallel effects on peripheral tissues. Compared to the suppressive T4 treatment dose, the addition of TRIAC to the physiologic T4 dose resulted in greater inhibition of TSH secretion in only 50% of the patients. The effects at the periphery of both treatment modalities were similar for a comparable level of TSH suppression. CONCLUSIONS: Even at low dose and when combined with T4, TRIAC has parallel effects on the pituitary and peripheral tissues. There is no justification for the use of TRIAC as suppressive treatment in thyroid cancer patients. PMID- 1934527 TI - Clonidine pretreatment modifies the growth hormone secretory pattern induced by short-term continuous GRF infusion in normal man. AB - OBJECTIVE: The aim of this study was to investigate the effect of a single dose of clonidine on the pattern of GH release in response to a 10-hour continuous GRF infusion in normal man. DESIGN: Plasma GH was analysed in samples withdrawn at 20 minute intervals, from 0900 to 1900 h, according to the following protocols: in a control study, a placebo was given at 1000 h; in other experiments, clonidine (300 micrograms, orally) was given at 1000 h, alone or together with a continuous intravenous infusion of GRF 1-29 (0.3 micrograms/kg/h) starting at this time. In another experiment, the continuous infusion of GRF 1-29 was preceded by placebo administration at 1000 h. PATIENTS: Eight normal volunteers (four women and four men), aged 19-24 years were studied. MEASUREMENTS: Plasma GH levels were measured by RIA. Analysis of the pattern of GH secretion was performed using cluster analysis. RESULTS: Clonidine induced a slight but significant increase in plasma GH values, peaking 60 to 120 minutes later; however, no significant changes were observed in indices of total and pulsatile GH release for the whole sampling period in this study. Continuous GRF administration led to increased episodic GH secretion, by augmenting GH peak amplitude, although peak frequency was not modified. An increase in interpulse GH values was also observed during GRF infusion. Pretreatment with clonidine clearly changed the pattern of GH release during GRF infusion: the amount of GH secreted was significantly higher, the number of GH peaks significantly increased, and almost all the GH was secreted within them. CONCLUSIONS: These data concord with our previous demonstration that clonidine disrupts the hypothalamic-somatotroph rhythm by inhibiting the hypothalamic release of somatostatin. Given that clonidine pretreatment induced a more physiological episodic pattern of GRF-induced GH release, the possibility of combining clonidine and GRF therapy for short stature in children is envisaged. PMID- 1934528 TI - GH response to growth hormone releasing hormone and hypoglycaemia is unaltered by high endogenous plasma calcitonin levels in patients with medullary thyroid carcinoma. AB - OBJECTIVE: As it has previously been reported that calcitonin suppresses stimulated growth hormone release, we have studied the serum growth hormone response to growth hormone releasing hormone and insulin-induced hypoglycaemia in patients with high calcitonin levels due to medullary carcinoma of the thyroid. DESIGN: Growth hormone releasing hormone (100 micrograms i.v.) and insulin (0.15 units/kg i.v.) were given and the growth hormone responses in the patients with medullary carcinoma of the thyroid and normal healthy controls were compared. PATIENTS: Eight with histologically confirmed medullary thyroid carcinoma, two females and six males, aged 21-77 years, were studied and compared with seven healthy age and sex matched controls. MEASUREMENTS: Growth hormone and calcitonin were measured. RESULTS: No significant difference was found between the growth hormone responses observed in patients with medullary carcinoma when compared with normal controls either after GHRH or during insulin-induced hypoglycaemia. CONCLUSION: We conclude that calcitonin does not alter the pituitary response to GHRH in medullary thyroid carcinoma and is unlikely to play an important role in regulating growth hormone secretion because calcitonin did not modify the release of growth hormone after insulin-induced hypoglycaemia. PMID- 1934529 TI - Effect of pyridostigmine and pirenzepine on GH responses to GHRH in hyperthyroid patients. AB - OBJECTIVE: We wished to investigate whether thyrotoxicosis can influence the cholinergic modulation of GH secretion. DESIGN: Pyridostigmine was given orally, then GHRH injected i.v., and levels were measured. In a separate study, pirenzepine was injected i.v., then GHRH, and growth hormone levels were measured. PATIENTS: Thyrotoxic patients were compared with normal subjects. MEASUREMENTS: GH was measured from -30 to +120 minutes at intervals of 15 minutes. RESULTS: Pyridostigmine markedly increased GH responses to GHRH in normal subjects, but not in thyrotoxic patients. Pirenzepine abolished the GH response to GHRH in thyrotoxic patients. CONCLUSIONS: GH responses to GHRH in hyperthyroid patients were suppressed by cholinergic muscarinic receptor blockade with pirenzepine. Activation of cholinergic pathways with pyridostigmine did not increase GH responses to GHRH in these patients. This may be a consequence of increased hypothalamic cholinergic function or reduced hypothalamic GHRH activity in hyperthyroidism. Our findings demonstrate a further mechanism by means of which thyroid status may affect the secretory activity of the somatotroph. PMID- 1934530 TI - Biochemical and hormonal changes induced by one week of administration of rIGF-I to patients with Laron type dwarfism. AB - OBJECTIVE: The purpose of this investigation was to evaluate the effectiveness of short-term administration of recombinant biosynthetic IGF-I on patients with an hereditary inability to generate this hormone. DESIGN AND PATIENTS: Ten patients with Laron type dwarfism (LTD) (4 males, six females) aged 3 1/2 to 37 3/4 years were submitted to seven daily s.c. injections of recombinant IGF-I in doses of 120 or 150 micrograms/kg/day. MEASUREMENTS: Blood samples were drawn before, after three and seven injections, and one week after stopping the trial. RESULTS: The main biochemical and hormonal changes registered were (mean +/- SD): a marked rise in serum type III procollagen (PIIINP) from 4.2 +/- 0.9 to 7.3 +/- 2 micrograms/l (P less than 0.0003) and decrease in the following blood components: plasma hGH from 32.51 +/- 43.77 to 4.02 +/- 2.48 mU/l (P less than 0.001), serum cholesterol from 5.9 +/- 1 to 5.7 +/- 0.8 mmol/l (P less than 0.04), serum SGOT from 28.9 +/- 11.6 to 15.5 +/- 7.6 U/l (P less than 0.01) and serum LDH from 286 +/- 88 to 222 +/- 37 U/l (P less than 0.0005). The response of plasma insulin was variable, decreasing in seven of ten and increasing in three. Some of these effects were transitory, and were found after 3 days therapy but afterwards decreased (insulin, cholesterol and liver tests), others persisted throughout the whole treatment period (hGH, PIINP). CONCLUSIONS: IGF-I mimics the biochemical and hormonal changes described after administration of hGH. The administration of IGF-I in patients with Laron type dwarfism is devoid of side-effects and warrants assessment in long-term studies. PMID- 1934531 TI - Cell kinetics in parathyroid adenomas: evidence for decline in rates of cell birth and tumour growth, assuming clonal origin. AB - OBJECTIVE: We aimed to provide a cell kinetic explanation for the demonstrated lack of disease progression in most patients with mild, asymptomatic primary hyperparathyroidism. DESIGN: We compared cell birth rates, estimated at the time of adenoma excision, with the lowest birth rates needed to grow tumours of the observed size. PATIENTS: Sixty-three patients with primary hyperparathyroidism due to a single chief cell adenoma who had normal renal function were followed up for long enough to demonstrate cure after surgical excision. MEASUREMENTS: Fresh adenoma tissue was incubated with tritiated thymidine. The proportion of cells synthesizing DNA was determined directly by radioautography in 18 cases, and indirectly from the regression of label index on rate of DNA synthesis in 45 cases. The birth rate of new cells was calculated assuming the duration of S phase to be 12 hours. The number of cells in each adenoma was estimated both from parenchymal weight and from total DNA content, and the minimum birth rate needed to produce this number of cells from a single cell, beginning in utero, was calculated on an exponential model. RESULTS: The mean observed birth rate of new cells (mean (SD)) was 17.3 (11.1)%/year, and the minimum needed birth rate was 42.8 (21.6)%/year, significantly, (P less than 0.001) higher than the observed birth rate. CONCLUSIONS: The rate of mitosis had fallen substantially during the life span of most parathyroid adenomas. To account for this, we propose that the mutation implied by a clonal origin increases the secretory setpoint. Because proliferation, as well as hormone secretion, is influenced by calcium in parathyroid cells, the expected result would be rapid initial growth, slowing down as tumour size reached an asymptotic value corresponding to the total rate of hormone secretion needed to raise the plasma calcium to the new setpoint. PMID- 1934532 TI - Effects of hypo or hyper-thyroidism on growth hormone-binding protein. AB - OBJECTIVE: Growth hormone (GH) receptors are influenced by the thyroidal state of experimental animals. It has been suggested that GH-binding protein (BP) might serve as an indirect measure of the GH receptors. The present study was undertaken to investigate the growth hormone binding protein in patients with hypo or hyperthyroidism. PATIENTS: Patients included 42 adults with untreated hyperthyroidism (FT4 greater than 25 pmol/l; TSH less than 0.15 mU/l) and 29 adults and three children with untreated hypothyroidism (FT4 less than 10 pmol/l; TSH greater than 15 mU/l). MEASUREMENTS: Growth hormone binding protein was measured by a binding assay with dextran-coated charcoal separation. The specific binding of 125I-human GH (1 ng) obtained with 50 microliters serum was expressed as a percentage of the total c.p.m. RESULTS: Growth hormone binding protein specific binding in hypothyroid adults and children was significantly lower than in their respective controls in both adults and children (P less than 0.001). In patients with FT4 levels greater than 40 pmol/l, the mean (+/- SEM) growth hormone specific binding (12.89 +/- 0.59%) was higher than in controls (P less than 0.05). However, in 15 hyperthyroid patients with levels of FT4 of 25-40 pmol/l, the mean growth hormone binding protein specific binding (11.22 +/- 0.76%) was not different from that in normal human subjects. The affinity constants (Ka) obtained by Scatchard analysis for the hypothyroid and hyperthyroid patients' sera were not significantly different from that for normal human sera. Binding capacity for the hypothyroid sera was significantly lower (P less than 0.02), while that of hyperthyroid sera was increased (P less than 0.001). CONCLUSIONS: Growth hormone binding protein correlates positively with the thyroid status. It can be indirectly deduced that this reflects a similar relationship with the human GH receptor. PMID- 1934533 TI - The influence of ketoconazole on human adrenal steroidogenesis: incubation studies with tissue slices. AB - OBJECTIVE: The influence of ketoconazole on the various enzymes of human adrenal steroid biosynthesis was examined in vitro. MEASUREMENTS: After incubation of human adrenal tissue slices with labelled precursors and ketoconazole (0-2000 microM), radioactive metabolites were separated by thin-layer chromatography and quantified by liquid scintillation counting. Enzyme activity was assessed by measuring conversion of tritium-labelled precursors to products. RESULTS: In vitro, ketoconazole showed a significant inhibition on the following adrenal enzyme systems (with decreasing activity): C17,20-desmolase (IC50 2 microM), 16 alpha-hydroxylase (IC50 9 microM), 17 alpha-hydroxylase (IC50 18 microM), 18 hydroxylase (IC50 28 microM), and 11 beta-hydroxylase (IC50 35 microM). In the tested concentrations ketoconazole had no inhibitory effect on the 21 hydroxylase, the 3 beta-hydroxysteroid dehydrogenase and the 20-hydroxysteroid dehydrogenase component of the C17,20-desmolase enzyme system. CONCLUSIONS: The data are in accordance with clinical findings where a strong suppression of serum androgen levels by relatively selective inhibition of C17, 20-desmolase has been assumed. The predominant blocking effect of ketoconazole on adrenal as well as on gonadal androgen biosynthesis might be of clinical benefit in the management of hyperandrogenic states. PMID- 1934534 TI - Laron-type dwarfism with apparently normal high affinity serum growth hormone binding protein. AB - OBJECTIVE: Normal serum contains a high affinity GH-binding protein, which appears to be identical with the extracellular domain of the GH receptor. It is normally absent from the serum of patients with Laron-type dwarfism. We wished in this study to define the serum GH-binding protein status of a family with Laron type dwarfism. DESIGN AND PATIENTS: We performed an open case study of an Asian family in which three sisters (aged 3 to 15 years) had the phenotype of Laron type dwarfism. Sera from a fourth, unrelated girl with Laron-type dwarfism and subjects without endocrine disorders were used as control samples. MEASUREMENTS: Laron-type dwarfism was confirmed by demonstration of elevated serum GH levels and low serum IGF-I levels on immunoassay, with serum IGF-I levels failing to rise during treatment with GH. Serum GH-binding proteins were characterized using gel chromatography on Sephacryl S-100HR following incubation of serum with 125I GH, Scatchard analysis of ligand binding, and by polyacrylamide gel electrophoresis after covalent cross-linking to 125I-GH. RESULTS: All members of the family had high affinity serum GH-binding protein activity similar in size, circulating levels and apparent affinity for GH to that of normal subjects. This contrasted with the very low serum GH-binding protein activity in the unrelated child with Laron-type dwarfism and previous reports of serum GH-binding protein levels in this disorder. CONCLUSIONS: The affected patients may possess a novel biochemical defect which results in GH-resistance and reduced production of IGF-I in the presence of normal serum GH-binding protein levels. PMID- 1934535 TI - Effects of consecutive doses of GHRH on GH secretion. PMID- 1934536 TI - Increased sensitivity to arousal in spontaneously hypertensive rats is partially dependent upon the amygdala. AB - This study was designed to determine the effects of behavioral arousal on baroreflex regulation of heart rate in stroke-prone SHR (spSHR) and to ascertain whether the integrity of the amygdala is necessary to mediate these effects. Heart rate responses to phenylephrine-induced increases in arterial pressure were used as an index of baroreflex sensitivity (BRS). spSHR had reduced BRS compared to WKR. Electrical stimulation of the amygdala suppressed BRS in conscious rats only at intensities that elicited behavioral arousal. When normalized for control bradycardiac responses, the spSHR demonstrated a greater suppression of BRS upon amygdalar stimulation than Wistar-Kyoto rats (WKR). Confrontation with a mouse, used to elicit behavioral arousal, attenuated BRS in both spSHR and WKR. Ablation of the central nucleus of the amygdala and adjacent tissue prevented confrontation-induced suppression of BRS both in WKR and spSHR. These data suggest that spSHR are more sensitive to suppression of BRS due to arousal elicited by stimulation of the amygdala. Furthermore, the amygdala is necessary for arousal-induced suppression of BRS in WKR and spSHR. PMID- 1934537 TI - Differential modulation of norepinephrine-induced contractile response by ryanodine and verapamil in the isolated aortic ring of spontaneously hypertensive and Wistar-Kyoto rats. AB - Using ryanodine and verapamil, we compared the relative contributions of SR Ca2+ release and gated Ca2+ entry in arterial contractions induced by norepinephrine (NE) between spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Aortic rings of 10 SHR and 10 WKY aged 10-12 weeks were superfused in small water jacketed tissue chambers with physiological salt solution and isometric tension was measured. The inhibition of the NE (3 x 10(-8) M)-induced contraction of aortic rings by ryanodine (10 microM) was significantly greater in WKY (40.1 +/- 6.9%) than in SHR (2.2 +/- 9.0%) (p less than 0.01). The inhibition of the NE induced contraction by verapamil (10 microM) in the presence or absence of ryanodine (10 microM) was significantly greater in SHR than in WKY. The residual ryanodine and verapamil-insensitive component of NE-induced contraction was significantly greater in WKY than in SHR. Caffeine (5 mM)-induced contraction in the presence of verapamil and phentolamine was significantly smaller in SHR than in WKY. These results suggest that gated Ca2+ entry plays a more important role in Ca2+ control and that ryanodine-sensitive Ca2+ store is smaller, or the ryanodine receptor is altered in these tissues of SHR compared with those of WKY. PMID- 1934538 TI - Ketanserin in the treatment of hypertension: a multicentre dose-finding study in China. AB - The effect of ketanserin at 5 mg, 10 mg and 20 mg twice daily for 3 months was studied in Chinese patients with hypertension. Both 10 mg and 20 mg doses twice daily effectively reduced systolic and diastolic pressures, while 5 mg twice daily was not effective. The 20 mg regimen was more effective than 10 mg in reducing diastolic, but not systolic pressures. Blood pressure reduction was progressive up to 1 month of treatment but not thereafter. Neither first-dose hypotension nor postural hypotension were seen. There were no effects on body weight or heart rate. A nominally significant 6 msec increase in QTc was seen with 10 mg, but not with 5 or 20 mg twice daily; this could be a chance finding. The side-effect burden was light, and decreased with time. PMID- 1934539 TI - Age-dependent salt-induced hypertension in the rat: prevention with DSP-4, a selective noradrenergic neurotoxin. AB - The present study was performed to determine if chronic administration of a high salt diet induces hypertension similarly in young and adult rats and if treatment with DSP-4 alters the development of the hypertension. Three- (young) and ten- (adult) week-old male Sprague-Dawley rats were fed either a standard rat chow diet (0.71% NaCl), a 4% NaCl diet or an 8% NaCl diet for 12 weeks. Systolic blood pressure, using a standard tail-cuff technique, and body weight were recorded weekly during the dietary treatment period. Direct mean arterial pressure, heart rate, heart weight and kidney weight were determined after 12 weeks. Body weight was slightly reduced in young rats on the 8% NaCl diet. A significant increase in blood pressure as well as heart weight was observed only in young rats on the 8% NaCl diet. An increase in kidney weight was observed in both young and adult rats on the 8% NaCl diet. DSP-4 treatment prevented the development of hypertension as well as cardiac hypertrophy in rats fed the high salt diet but had no effect on rats receiving the normal diet. Body and kidney weights were similar in vehicle- and DSP-4-treated rats on the 8% NaCl diet. These results demonstrate that a critical developmental/maturational period exists during which the young rat is susceptible to the hypertensinogenic effects of a high salt diet. An intact central noradrenergic system appears to be necessary for the expression of this enhanced susceptibility and the subsequent development of hypertension. PMID- 1934540 TI - Blood pressure development in F2 rats derived from SHR and WKY progenitors. AB - In adult humans blood pressure measurements taken at one point in time are significantly correlated with subsequent measurements. However, during development, 'tracking' of blood pressures is relatively poor thus, accurate prediction of hypertension can only be made much later in life. To find better early life predictors of adult hypertension, studies using the F2 generation of rats derived from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) grandparents have been initiated. Characteristics of blood pressure development in the F2 population suggest they will be a suitable model for this goal. F2s express a wide range of adult blood pressures but, as is the case in humans, stability of individual ranking within the population, is not present until after puberty. Other results indicate that adult body weight, heart rate, and temperature are not genetically linked to SHR hypertension, and that measurement of these variables early in life, with the possible exception of body weight early in life, can not be used to predict adult hypertension. PMID- 1934541 TI - Characterization of alterations of hemodynamics and neuroendocrine hormones in dexamethasone induced hypertension in dogs. AB - The serial changes in systemic and renal hemodynamics, water and electrolyte balances and various vasoactive hormones were examined in 12 conscious dogs before, during (10 days) the administration of dexamethasone (DEX: 0.5 mg/kg/day) and after the cessation of DEX. In addition, during the administration of DEX, pressor responses to angiotensin II, norepinephrine, an angiotensin II analogue, saralasin, and an alpha-1-blocker, prazosin, were studied. Abrupt elevation of blood pressure to 106 +/- 5 mmHg on Day 1 (vs. 91 +/- 6 mmHg control: P less than 0.05) associated with marked increases in total peripheral resistance (P less than 0.01) was shown in DEX treated animals. Accompanied with these changes, renal blood flow increased to 146 +/- 12 ml/min (vs. 103 +/- 8 ml/min control: P less than 0.05) on Day 1 and maintained. In contrast, the results of serial alterations in hormones could not show any significant changes except significant elevations in atrial natriuretic peptide and reductions of cortisol and arginine vasopressin. Also, marked natriuresis and diuresis were observed in DEX administration dogs. Pressor response to norepinephrine was significantly increased and administration of either saralasin and prazosin significantly reduced the blood pressure of DEX treated animals. These results in DEX-treated conscious dogs confirmed our previous findings in human and rats. Glucocorticoid induced hypertension mainly depends on the increases in total peripheral resistance but not volume factors. PMID- 1934542 TI - A new approach to quantify cardiovascular response in dentistry. AB - Essential hypertension, which is common in dentists, has been attributed to mental stress but the importance of working conditions has not been evaluated. The pressor and forearm circulatory response to correct and incorrect working position during dental practice has been evaluated in 10 normotensive dentists and compared with the effects of mental stress. Mental stress elicited a significant increase in blood pressure not observed during correct dental practice despite a comparable forearm vasodilatation during both tests. Conversely incorrect working position, significantly raised blood pressure to an extent comparable to what observed during mental stress but with only a transitory and rapidly abolished forearm vasodilatation. The recordings of blood pressure or peripheral hemodynamic changes per se did not allow to discriminate between a specific response to mental stress and dental practice which, were clearly differentiated by the analysis of combined pressor and hemodynamic measurements. We conclude that odontoiatric practice carried out in an incorrect working position is able to elicit either an increase in blood pressure or abnormalities in peripheral vascular response which may contribute to the high occurrence of systemic hypertension in dentists. The evaluation of peripheral hemodynamic profile during working conditions seems to provide a useful method for a better understanding of the pattern of cardiovascular involvement in dentistry. PMID- 1934543 TI - Facial palsy. PMID- 1934544 TI - The use of ventilation tubes in secretory otitis media: a review of consultant otolaryngologists. AB - A questionnaire concerning various aspects of secretory otitis media was completed by a random sample of Consultant Otolaryngologists in the United Kingdom. The replies to questions associated with the use of ventilation tubes are presented. The results suggest a wide disparity associated with their use and these findings are discussed with reference to current research. PMID- 1934545 TI - Adult epiglottitis: is there a consensus on diagnosis and treatment? AB - Adult epiglottitis is a different disease from that seen in paediatric patients both in the clinical picture and management. This paper presents 6 cases of adult epiglottitis which resulted in 2 deaths despite 3 patients having airway intervention. After reviewing some of the larger published series of adult epiglottitis in an attempt to find a consensus on management, a number of recommendations can be made: (1) indirect laryngoscopy is an essential diagnostic step which is safe in the adult and is more reliable than a lateral neck radiograph; (2) bacteriology specimens play no part in acute management and antibiotics must be given empirically; (3) adrenaline may be of value in avoiding airway intervention; (4) airway intervention must be a clinical decision and the conditions for its successful outcome made as favourable as possible by realizing that all patients can rapidly develop life threatening respiratory obstruction. An 'intensive care' level of clinical monitoring and early involvement of experienced ENT and anaesthetic staff is recommended. PMID- 1934547 TI - Free flaps in head and neck reconstructive surgery: a review of 77 cases. AB - Recent advances in surgical technique and instrumentation have ensured that success rates for microvascular free transfer can now exceed 90%. This paper reviews a prospective study of 77 free flaps performed at the Royal Marsden Hospital under the care of one surgeon (NMB) over a 2-year period. 76 patients who underwent 77 free flaps were studied. 68 patients had malignant tumours and 8 had benign lesions. The flap success rate was 95% and the mortality rate 0%. The major complication rate was 20% and the most common complication was a salivary fistula (12%). Microvascular free transfer to the head and neck is not associated with increased morbidity and mortality. It offers single stage, reliable, effective reconstruction using a wide variety of donor sites and tissues. PMID- 1934546 TI - Pain relief after tonsillectomy in adults: intramuscular diclofenac and papaveretum compared. AB - A wide variety of surgical and pharmacological methods have been described in an attempt to reduce pain after tonsillectomy, with conflicting results. Opiates are still widely used, despite unwanted side-effects. Recently the non-steroidal anti inflammatory drugs have been shown to be effective against a variety of post operative pains. Diclofenac is effective in both children and adults in the relief of pain after tonsillectomy when administered rectally, but absorption is variable, and suppositories are not widely accepted in the UK. The present double blind study compared a single intramuscular dose of diclofenac with papaveretum in adults undergoing tonsillectomy. Post-operatively, the patients who received diclofenac had less pain and started drinking significantly sooner than the control group. There were no undesirable side-effects. Intramuscular diclofenac is superior to papaveretum in the relief of pain in adults undergoing tonsillectomy. PMID- 1934548 TI - Otitis media with effusion in children shows a progressive resolution with time. AB - The course of chronic otitis media with effusion (OME) was studied in 117 children (207 ears). Diagnosis was based on otoscopy and a flat (type B) tympanogram. This was compared with the presence or absence of middle ear effusion at myringotomy carried out 0-3, 3-6, 6-9 and more than 9 months after diagnosis. There was a highly significant reduction in the number of effusions diagnosed at myringotomy in those patients who had waited longer for operation. The effects of previous ventilation tube insertion, adenoidectomy, medical treatment between diagnosis and operation, month of diagnosis and month of admission on the results were examined. Tympanosclerosis and atelectasis occurred in 7.3 and 6.3% of ears respectively and in most cases were associated with previous grommet insertion. PMID- 1934549 TI - Carcinoma in situ of the larynx: an evaluation of its natural clinical course. AB - The outcome of 75 patients with severe dysplasia or carcinoma in situ of the larynx has been reviewed. The patients were divided into three groups according to treatment; Group A (16 patients) had received irradiation. Group B (24 patients) had developed invasive carcinoma less than 1 year after the diagnosis of carcinoma in situ and Group C (41 patients) had been observed for more than 1 year, receiving no treatment other than repeat biopsies. Of the latter group, 46% developed invasive carcinoma of the vocal cords, with a mean observation time of 51 months. Mean age at the onset of the disease was 66 years in patients where the epithelium returned macroscopically to normal during observation compared to 59 years in patients who developed carcinoma (P less than 0.05). This may indicate that subgroups of carcinoma in situ exist with different biological behaviour. No extra benefit was seen for the patients who received irradiation for carcinoma in situ, and close follow-up with, eventually, stripping of the epithelium is therefore advocated. Both altered anatomical site during observation and an increase in area of the lesion should be regarded as a warning signal. PMID- 1934551 TI - The clinical management of otorrhoea following grommet insertion: a survey of otolaryngologists and general practitioners. AB - A postal questionnaire of all Consultant Otolaryngologists in the British Isles, and of General Practitioners within the local family practitioner committee area, was designed to compare the current practice in the management of discharge from the ear following grommet insertion. 76% of the Otolaryngologists and 52% of the General Practitioners completed the questionnaire. Between the two groups, statistically significant differences were apparent in the management of this common complication of grommet surgery. A higher proportion of Consultants took a bacteriology swab of the ear as part of their treatment, which was significantly more frequently treated by antibiotic ear drops. Within the Consultant group, significant regional variations in choice of drugs and therefore the cost of treatment were apparent. The General Practitioners more commonly prescribed oral antibiotics. This common complication of grommet surgery is managed differently by General Practitioners and Otolaryngologists without a firm rational basis. Treatment based on current knowledge is discussed. Further evaluation of the efficacy of different treatment regimens by controlled prospective trials is required. PMID- 1934550 TI - Chronic otitis media and ankylosing spondylitis: an HLA association? AB - A prospective study was undertaken to investigate an apparent correlation between ankylosing spondylitis (AS) and the incidence of otological conditions. 42 consecutive patients attending the ankylosing spondylitis clinic were examined otoscopically and had audiometric assessment. 19% of the patients (8/42) had active or inactive chronic otitis media. The prevalence of chronic otitis media in this group was significantly greater (P less than 0.01) than a stratified sample of the general population from the Medical Research Council Institute of Hearing Research National Study of Hearing, controlled for age, sex and socio economic group, where the expected incidence was 5%. A hypothetical explanation for the association is given and the need for HLA studies into chronic otitis media is discussed. PMID- 1934552 TI - A trial of tinnitus therapy with ear-canal magnets. AB - A double-blind trial of Takeda's treatment of tinnitus by placing rare-earth magnets close to the tympanic membrane was carried out on 50 patients. The trial failed to show significant benefit from this line of therapy. PMID- 1934553 TI - Auditing the reliability of recall of patients for minor surgical procedures. AB - The aim of this study was to document the reliability of patients in an ENT clinic for the history of previous operations and to investigate the effect of asking more detailed questions. 162 Patients were questioned using one of two questionnaires, followed by examination. The results of the survey call in question the reliability of the history of previous surgery, particularly of procedures performed in childhood or regarded as minor. Thirty-eight patients did not admit to having undergone dental extraction under general anaesthetic until directly questioned. No male patients admitted to genitourinary surgery unless directly questioned. Four out of 84 patients did not admit to tonsillectomy until directly questioned and a further 5 patients were discovered to have undergone tonsillectomy only by examination, despite direct questions. In conclusion, this study illustrates the importance of direct questioning and highlights the poor reliability of some patients in revealing surgical procedures under general anesthetic which may be regarded as trivial. PMID- 1934554 TI - Vagal paragangliomas: a clinical, pathological, and DNA assessment. AB - Ten vagal paragangliomas were studied by image analysis and the results correlated with clinicopathologic features to determine if the DNA ploidy pattern could be used to separate benign from malignant paragangliomas. The tumours occurred in 8 women and 2 men ranging in age from 23 to 75 years (average 54 years). Follow-up was available in all 10 patients and ranged from 3 months to 27 years (average 7.8 years). Of the 10 tumours examined for DNA, 5 were diploid, 4 diploid-tetraploid, and 1 aneuploid. Two patients experienced local recurrences. One of these had a diploid tumour that recurred 22 years after excision and the other had an aneuploid tumour which recurred 4 years 4 months later and was associated with cervical lymph node metastasis. Two patients had malignant tumours with histologically confirmed metastases to noncontiguous cervical lymph nodes. One of the malignant tumours was diploid and the other aneuploid. This study concludes that DNA abnormalities are common in vagal paragangliomas and that tumour ploidy can not be used to assess malignant potential. PMID- 1934555 TI - Evaluation of a new method of neural anastomosis using nitrocellulose paper. AB - Nerve regeneration was examined in 108 mouse sciatic nerves in a prospective morphometric study in which a new anastomotic technique using nitrocellulose paper was compared with conventional suturing and simple sectioning. Mice were randomly allocated to one of the three arms of the trial and sciatic nerves were examined following surgery at time intervals up to 8 weeks. Serial sections were taken for qualitative and quantitative morphometric analyses. Counts demonstrated that the rate of regeneration was faster in the nitrocellulose group than following nerve section alone, but that the suture group was even better. However, 8 weeks after surgery, there were no significant differences in myelinated axon counts 4mm distal to the site of section between any of the experimental groups. The superlative regenerative capacity of rodent axons may limit the applicability of this model to human nerve tissue. PMID- 1934556 TI - Intranasal balloon catheters: how do they work? AB - Despite there being a wide range of different epistaxis balloons their mode of action is unknown. Manufacturers' drawings depict balloons neatly filling the nasal cavity or precisely occluding the anterior and posterior nasal apertures. In view of the complexity of nasal internal anatomy these explanations seem unlikely. A better understanding of the configuration of these devices within the human nasal cavity may explain their mode of action and complications. This study aimed to delineate radiographically the configuration of 3 commonly used balloons within the noses of 4 human cadavers and to observe the effects of alterations in inflation volumes. The results showed that devices designed to fill the nasal cavity do not achieve this aim. Balloons do not conform to the contours of the nasal cavity but expand along pathways of least resistance and prolapse into the nasopharynx. The findings may explain the occurrence of complications such as headache and Eustachian tube obstruction. Accurate nasal tamponade is unlikely to be their true mode of action. These devices probably work by a combination of factors rather than as a result of specific design features. The possibility of rational design modifications is discussed. PMID- 1934557 TI - Workload trends in otolaryngology: some statistical observations from medical record linkage. AB - Trends in admission rates, lengths of stay, and clinical case mix (adjusted for multiple admissions per person) for Otolaryngology from 1975 to 1985 are described using the Oxford Record Linkage Study. Person-based admission rates increased generally, most strikingly amongst children and adolescents. Both length of stay per episode and total number of days an individual stayed in hospital each year decreased. Operations on tonsils and adenoids decreased averaging 2.2% per annum; admissions for diagnoses for otitis media with effusion increased averaging 8.2% per annum; for the operations of myringotomy and tympanostomy tube insertion increased averaging 9.2% per annum; for other diagnoses related to the ear increased averaging 5.7% per annum; and admissions for malignant neoplasms decreased averaging 2.0% per annum. Clearly more people are being treated for a changing case mix. The largest increases are occurring with children and adolescents. PMID- 1934558 TI - The effect of intensity on combined glottography. AB - This study investigates the relationship between intensity and the open quotient (OQ) and speed quotient (SQ) values of combined glottography. Simultaneous electroglottography and photoglottography were performed on 20 healthy male subjects at intensities of 55 and 65 dB. Paired t-test statistical analysis showed that the open quotient varies inversely and the speed quotient directly with the intensity. When reporting findings it is therefore necessary to state the intensity at which the results were obtained. PMID- 1934559 TI - Obstructive sleep apnoea in adults presenting with snoring. AB - Snoring is a common disorder, and may be associated with obstructive sleep apnoea, although there is little published information on the incidence of apnoea in snorers. This study aimed to assess the upper airway and to relate the findings to sleep study data in a population of patients referred by their general practitioners with loud snoring. Each patient had a full history, weight and height measurements, nasal examination, rhinomanometry, peroral grading of the oropharyngeal features, and fibreoptic pharyngoscopy with a modified Muller manoeuvre, followed by a sleep study. The results in our group of 35 patients demonstrate a high incidence of obstructive sleep apnoea (46%). Factors which correlated well with apnoea were excessively loud snoring, a narrow oropharynx, and marked obesity; 94% of patients with one or more of these features had evidence of sleep apnoea. PMID- 1934560 TI - Occupational factors in the aetiology of head and neck cancer. PMID- 1934561 TI - The Edinburgh FESS Trainer: a cadaver-based bench-top practice system for endoscopic ethmoidal surgery. AB - Functional endoscopic sinus surgery (FESS) requires cadaver-based practice to acquire the necessary technical expertise. To enable this to be undertaken as a bench-top activity the Edinburgh FESS Training system has been developed. This involves the en-bloc removal of the relevant parts of the nasal cavity and sinuses from cadavers and their embedding and mounting in a simulated head. PMID- 1934562 TI - Immediate-pressure urticaria--a distinct disorder. AB - We report a patient who has an immediate wealing response to pressure in the absence of symptomatic dermographism, which we designate 'immediate-pressure urticaria'. Our patient also suffered from cholinergic urticaria and chronic idiopathic urticaria in the past, demonstrating the clustering of urticarias which frequently occurs. PMID- 1934563 TI - Familial acquired pigmented streaks in the nail. AB - A 40-year-old man developed multiple longitudinal pigmented streaks in his nails. His sister was also found to have a single streak on a fingernail. Neither had any history of drug ingestion or recent illness and examination failed to reveal any other signs in the skin or mucosal surfaces. A biopsy of the nail matrix at the base of one streak showed no evidence of a naevus or lentigo, the principal finding being pigmentary incontinence and excess macrophages. PMID- 1934564 TI - Chronic bullous dermatosis of childhood--clinical and immunological features seen in African patients. AB - During the period 1985-88, 30 children with a chronic blistering dermatosis were studied. Of these 25 were found to have chronic bullous dermatosis of childhood (CBDC) and five had bullous pemphigoid (BP). No case of dermatitis herpetiformis (DH) was seen in the same period. Except for the difference in immunofluorescence (IMF) there were no definite clinical, histological or therapeutic differences between the two groups. All the children were Africans with the exception of one Indian girl. Their ages ranged from 1 year to 12 years with a mean of 5 years. The females outnumbered the males in a ratio of 3:2. All children had a generalized eruption consisting of large tense blisters arising on normal skin. The blisters were more profuse on the lower trunk, pelvic region and limbs. Face and scalp were also affected. Histological features of BP and DH were seen. Direct IMF in the CBDC patients showed linear deposits of IgA at the basement membrane zone (BMZ) while linear deposits of IgG were seen in the BP group. Complement and IgM were also seen in some cases in both groups. Sixty per cent of the CBDC patients showed IgA BMZ antibodies by indirect IMF. There were no symptoms or signs of malabsorption. Serum vitamin B12 and folate levels were normal. HLA studies showed the B-8 antigen in five of the 20 patients studied. Therapy was difficult in most cases. All patients haemolysed on therapeutic doses of dapsone, sulphapyridine and/or prednisone had to be added. Follow-up was generally poor as six patients failed to return after discharge from hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934565 TI - Bath-water delivery of 8-methoxypsoralen therapy for psoriasis. AB - Twenty-one patients with chronic plaque psoriasis were treated with bath 8 methoxypsoralen (8-MOP) and ultraviolet A (UVA). Clearing was achieved in sixty per cent of patients which was less than would be expected with oral 8-MOP. The treatment was well tolerated and was preferred by those who had previously been treated with oral psoralen. The cumulative dose of UVA was only one-fifth that expected with oral 8-MOP. PMID- 1934566 TI - Bioavailability of fluconazole and ketoconazole in human stratum corneum and oral mucosa. AB - In this study, the bioavailability of fluconazole and ketoconazole in the stratum corneum and oral mucosa after multiple oral dosages were compared. It is well recognized that such evaluation is heavily dependent on the test methods employed. A method of culture of fungi on human stratum corneum and superficial mucosal cells, a model close to the in-vivo situation, was used. A significant difference in the bioavailability of the two antifungals in stratum corneum and superficial cells of oral mucosa was found. The activity of ketoconazole proved to be more rapid against T. mentagrophytes while fluconazole appeared slightly more active against C. albicans. PMID- 1934567 TI - Increased HLA-DR+ T-lymphocyte population in peripheral blood of alopecia areata. AB - The populations of activated T-cell subsets [HLA-DR(+)-Leu 4+ cells, interleukin 2 receptor positive (IL-2R+)-Leu 4+ cells] in the peripheral blood of patients with alopecia areata (AA) were investigated using double direct immunofluorescence staining. Fifty-eight patients with AA were classified into one of three types: those with inactive single AA (type 1) lesions, active multiple alopecia areata (MAA) lesions and active alopecia totalis (AT) (type 2) and chronic alopecia universalis (AU) (type 3). Compared to normal controls, high percentages of HLA-DR(+)-Leu4+ cells were detected in types 2 and 3 AA patients, but not in type 1 AA patients. These findings suggest that T cells are activated in the peripheral blood of active MAA, AT and chronic AU. PMID- 1934568 TI - Pityriasis rubra pilaris in Singapore. AB - Fourteen patients with pityriasis rubra pilaris seen between 1981 and 1989 were evaluated retrospectively. There were nine male and five female patients. There was a bimodal age of onset in early childhood and in adulthood. All the patients had either follicular hyperkeratosis or hyperkeratosis of the palms and soles. Nine patients had erythroderma. The classical forms, either in the children or in the adult patients, were more likely to recover. Several treatment modalities were used and these included steroids, Vitamin A, etretinate, retinoic acid and ultraviolet light (UBV). Nine patients had complete recovery. Four of these patients received only steroids, two cleared while on vitamin A, two cleared while on etretinate and one cleared with methotrexate. PMID- 1934569 TI - Predictable and unpredictable hazards of erythropoietic protoporphyria. AB - A female patient with a long history of erythropoietic protoporphyria developed progressive rapid derangement of hepatic function requiring urgent orthotopic liver transplantation. In the immediate post-operative period the patient developed unusual and serious complications, including a generalized axonal neuropathy, intestinal ulceration and a large second-degree phototoxic burn of the abdominal wall. Recovery was achieved only after prolonged intensive hospital care and rehabilitation. Attention is drawn to the need for protecting such patients from phototoxic injury during prolonged surgery and the importance of rapid transfer to a specialized unit at the earliest sign of hepatic failure. PMID- 1934570 TI - Natural progression of male pattern baldness in young men. AB - Twenty-six men who presented with male pattern baldness (androgen-dependent alopecia), were quantitatively evaluated for scalp hair variables and compared with 13 age-matched controls. Compared to controls, significant mean differences for hair variables were found in the frontal-vertex area, while in the occipital area, a reduction in total hair density (hairs/cm2) was the only significant (P less than 0.05) finding. A large proportion (48.5%) of meaningful hair (non vellus hair) was less than or equal to 40 mm in length, yet had diameters similar to hairs growing much longer. In controls, these hairs accounted for only 12.2% of the total population. Compared to baseline, mean values from the frontal vertex area of subjects with androgen-dependent alopecia were significantly lower for total hair density, meaningful hair density (non-vellus hairs/cm2) and percentage of hair in the anagen growth phase, 12 and 24 months later. During this time, total hair density decreased by 6.5% after 12 months and by 11.9% after 24 months. Similarly, meaningful hair density declined at 12 months by 10.8% and by 22.7% after 24 months. No change in any hair variable was detected in controls after 12 or 24 months. Our findings suggest that medications capable of maintaining the existing hair population should be regarded as effective treatments for this condition. Left untreated androgen-dependent alopecia progressively deteriorates. The induction of non-vellus hairs less than or equal to 40 mm in length to grow longer, would substantially improve the aesthetic profile without the need to generate new hair. PMID- 1934571 TI - Autonomic and sensory nerve function in diabetic foot ulceration. AB - Peripheral sensory and autonomic nerve dysfunction are thought to be crucial factors in the pathogenesis of diabetic foot ulceration. However, their relative importance is not known. In this study we have compared peripheral sensory nerve function and cardiac autonomic reflexes in 51 diabetics with a history of foot ulceration and 480 diabetic control subjects. In the diabetics with ulceration ankle reflexes were absent or impaired and vibration perception threshold reduced in 96.1% and 82.4%, respectively, compared with 40.8% and 25.8%, respectively, in control subjects (P less than 0.001). Cardiac autonomic tests were abnormal more frequently in the diabetics with ulceration and an autonomic score derived from four tests was abnormal in 62.8% of those with ulceration compared with 13.5% of those without ulceration (P less than 0.001). Discriminant analysis of the two groups of diabetes showed that an abnormal autonomic score was the best predictor of foot ulceration in diabetic patients. PMID- 1934573 TI - Tufted-hair folliculitis. AB - A 21-year-old man presented with an erythematous pruritic plaque on the right parietal scalp of 2 years' evolution. Physical examination disclosed multiple bundles of hairs emerging from single dilated follicular openings. The disorder followed a relapsing and progressive course, in spite of several topical and systemic treatments. New tufts of hairs appeared in previously non-involved areas only after inflammatory changes occurred. The clinicopathological features, aetiological mechanisms and management of tufted-hair folliculitis are discussed. Tufted-hair folliculitis (THF) is a localized, inflammatory and exudative disease of the scalp characterized by a tufted appearance of the scalp hair, that may result in permanent and irreversible scarring alopecia. This condition was initially described by Smith and Sanderson in 1978 who coined the term THF to illustrate the phenomenon of multiple hairs emerging from single follicular openings. Only nine additional cases of THF have been reported elsewhere. We present herein a patient with recurrent and progressive THF resistant to several therapeutic strategies. PMID- 1934572 TI - Notalgia paraesthetica--report of three cases and their treatment. AB - Notalgia paraesthetica is a rare entity which involves the posterior primary rami of thoracic nerves T2-T6. Patients present with a localized discomfort or pruritus on the back. The condition runs a benign course and usually resolves spontaneously. However, whilst present the symptoms can be relentless and disturbing to patients. We report three patients with notalgia paraesthetica, all of whom were helped symptomatically by the topical application of the local anaesthetic cream, EMLA (2.5% lignocaine and 2.5% prilocaine). PMID- 1934574 TI - T-cell lymphoma presenting with severe digital ischaemia. PMID- 1934575 TI - Erythema elevatum diutinum--an unusual association with ulcerative colitis. AB - We report the association of erythema elevatum diutinum (EED) with ulcerative colitis (UC). The patient, whose history included rheumatoid disease, diabetes mellitus (type I) and hypothyroidism developed EED during a severe acute exacerbation of UC which resolved following colectomy. To our knowledge this is the first report of such an association. Also of interest was the observation of Koebner phenomenon occurring at the sites where blood vessels were damaged. PMID- 1934576 TI - Transient leukaemia cutis in hairy-cell leukaemia. AB - Leukaemic skin infiltration is uncommon in hairy-cell leukaemia (HCL), a neoplasm characterized by the presence of uniform mononuclear cells with cytoplasmic projections in the blood, bone marrow and spleen. A case is reported in which leukaemia cutis was a transient phenomenon, appearing soon after the onset of a continuous pyrexia associated with marked systemic upset which was subsequently shown to be due to pulmonary tuberculosis. PMID- 1934577 TI - Skin ulceration as sole manifestation of Langerhans-cell histiocytosis. AB - A 65-year-old black woman presented with skin ulceration of 5 years' duration which affected the left axilla, left groin, intergluteal folds and ano-perineal region. The diagnosis of Langerhans-cell histiocytosis (LCH) was confirmed by light and electron-microscopic findings and a positive S-100 stain. Extensive investigations failed to reveal any evidence of systemic involvement. A review of the literature suggests that this clinical picture as the sole manifestation of the disease is rare. PMID- 1934578 TI - Destructive granuloma annulare of the skin and underlying soft tissues--report of two cases. AB - Two cases of extensive cutaneous granuloma annulare (GA) associated with severe deformity and impairment of function in the involved extremity are described. In the first patient a mutilating, destructive arthritic condition and infiltrative oedema of upper extremities developed over the years along with florid disseminated GA of the tendons and overlying skin. In the second patient disseminated GA of one lower extremity resulted in diffuse induration and chronic lymphoedema. In both cases, histology showed palisading granulomas typical of GA at all levels of the dermis, subcutaneous tissues, fascia, and synovium. The unique clinical features of GA in both presented cases emphasize the local destructive potential and, as yet, poorly understood progression of GA to a soft tissue disease. PMID- 1934579 TI - Acromegaly and psoriasis. AB - A 56-year-old man with long-standing chronic plaque psoriasis was noted to be acromegalic. Investigations confirmed the presence of a large pituitary adenoma and following treatment of this by hypophysectomy his psoriasis cleared dramatically within 3 weeks. PMID- 1934580 TI - White fibrous papulosis of the neck. AB - We report a case of white fibrous papulosis of the neck in a 70-year-old Iranian woman. To date this recently reported entity has only been described in Japanese patients. This asymptomatic eruption characteristically affects the posterior neck. The pale papules are round to oval 2-3 mm in diameter, and not follicular. Histology shows thickened collagen bundles in the superficial and mid-dermis with a normal elastic pattern. PMID- 1934581 TI - Monilethrix treated with oral retinoids. AB - We report a childhood case of monilethrix in which oral etretinate was given. Clinically, the cosmetic benefit was marginal. However, of note was that there was an increase in hair length with loss of beading along the shaft of these hairs. The background scalp appearance of keratosis pilaris persisted in these areas. This suggests that the beading alone is influenced by etretinate and is not solely an artefact secondary to the hyperkeratotic condition at the follicular opening. PMID- 1934582 TI - Childhood pemphigus foliaceus. AB - We describe a girl who presented at the age of 12 years with a blistering eruption on the lower limbs. One week later, numerous new bullae and blisters were present. Skin biopsy for histology and immunofluorescent studies established the diagnosis of pemphigus foliaceus. PMID- 1934584 TI - Traumatic alopecia with discoid lupus erythematosus. PMID- 1934583 TI - Methotrexate and trimethoprim-sulphamethoxazole. PMID- 1934585 TI - Cryosurgery of hand warts. PMID- 1934586 TI - Venous hypertension complicating arterio-venous fistula construction. PMID- 1934587 TI - Childhood lichen planus. PMID- 1934589 TI - The H3 anti-phospholipid idiotype is found in patients with systemic lupus erythematosus (SLE) but not in patients with syphilis. AB - The human H3 idiotype, defined by a mouse monoclonal antibody S2.9, is commonly found in patients with SLE where it is correlated with the amount of anti cardiolipin antibodies. No correlation between the amount of anti-cardiolipin antibody and the H3 idiotype is found in patients with syphilis. Using the S2.9 antibody, serum from each of 10 patients with SLE and eight patients with syphilis was separated into H3-bearing and H3-negative fractions. Comparison of the partition of anti-cardiolipin antibody in these two groups of patients revealed that much of the anti-cardiolipin antibody (44-91%) was found in the H3+ fraction in patients with SLE; in patients with syphilis, virtually none of the anti-cardiolipin antibody was H3+. In patients with SLE, the H3+ fraction contained both IgG and IgM and antibodies of both kappa and lambda light chains. The H3+ fraction was polyspecific and frequently reacted with dsDNA. PMID- 1934588 TI - Intravenous immunoglobulins (IVIg) in the treatment of autoimmune diseases. AB - Intravenous immunoglobulin (IVIg) therapy is increasingly used in autoimmune diseases. Although its efficacy has only been established in a few specific antibody-mediated autoimmune conditions, accumulating evidence on the regulatory role of circulating immunoglobulins in the selection of peripheral B cell repertoires makes it an attractive potential therapeutic option to clinical immunologists. This overview briefly discusses the current use of IVIg in human autoimmune diseases with a particular emphasis on the possible mechanisms by which IVIg could suppress pathological autoimmune responses. PMID- 1934590 TI - Acquired resistance to type II collagen-induced arthritis in rhesus monkeys is reflected by a T cell low-responsiveness to the antigen. AB - Ten out of 14 rhesus monkeys developed arthritis after a single immunization with bovine type II collagen (B-CII). In contrast to primary resistant monkeys, arthritic animals showed a B-CII specific T cell proliferation during the induction phase of the disease. All surviving animals showed a full remission of the disease. Two monkeys acquired resistance to collagen-induced arthritis (CIA) after one period of disease, but in three animals a booster immunization with B CII induced a slight flare-up. It is demonstrated that B-CII immunized rhesus monkeys have the capacity to restore resistance to CIA. The development of resistance to CIA is reflected by a decreased T cell responsiveness to B-CII. It is shown that the lack of IL-2 plays a role in B-CII-induced T cell low responsiveness. A potential role of CD8+ T cells in the down regulation of the T cell response to B-CII is discussed. PMID- 1934591 TI - Enhanced serum levels of soluble HLA class I molecules are induced by treatment with recombinant interferon-gamma (IFN-gamma). AB - In order to investigate serum levels of soluble HLA class I antigens after single injection of various doses of recombinant IFN-gamma (rIFN-gamma) and to correlate the changes observed to beta-2-microglobulin serum levels, we studied five patients with metastasizing renal cell carcinoma. Each patient received three treatment cycles of 10, 100 and 500 micrograms rIFN-gamma three times at weekly intervals. The treatment cycles were separated by a therapy-free interval of 2 weeks. The order of dose levels was randomly assigned to each patient. Serum levels of soluble HLA class I proteins were measured by an ELISA in samples drawn immediately before and 4, 24, 48, 72 and 168 h after each administration of rIFN gamma. Beta-2-microglobulin was assessed in parallel using a commercially available radioimmunoassay. Significant induction of soluble HLA class I protein serum levels was observed after treatment with 100 and 500 micrograms rIFN-gamma. The increments peaked after 2-4 days and remained elevated for up to more than 7 days. A significant correlation between increments of soluble HLA class I proteins and beta-2-microglobulin was observed. We conclude that measurement of soluble HLA serum levels is practical for monitoring induction of HLA class I synthesis in patients treated with rIFN-gamma. The correlation observed between induction of beta-2-microglobulin and soluble HLA class I proteins indicates that measurement of beta-2-microglobulin might be sufficient for the biological response monitoring in clinical studies. PMID- 1934592 TI - Lactate dehydrogenase (LDH) isoenzymes and proliferative activity of lymphoid cells--an immunocytochemical study. AB - In a recent immunohistochemical study, we suggested that elevation of LDH isoenzymes is generally related to cell proliferation. To explore this relationship further, we have now examined the expression of H- and M-type LDH isoenzymes immunocytochemically in human resting and mitogen-activated B and T lymphocytes. In the resting state, T lymphocytes showed strong staining for H type LDH but showed little or no staining for M-type LDH, while B lymphocytes showed only weak staining for M-type LDH. During activation of T cells, M-type LDH started to increase when cells entered the early stages of the cell cycle. The staining intensity increased to a maximum when the percentage of the T cells at the S/G2/M phases of the cell cycle reached its peak. M-type LDH expression declined when the activated T cells returned to their resting state. Staining for H-type LDH remained strong in T cells during activation. In B lymphocytes, both H and M-type LDH isoenzymes increased concomitantly following activation and the staining intensity also correlated well with the percentage of the S/G2/M fraction. The expression of H- and M-type LDH was also determined in fresh leukaemia and a variety of lymphoid cell lines. It was noted that cells of chronic lymphocytic leukaemia (CLL) and pro-lymphocytic leukaemia (PLL), morphologically similar to normal lymphocytes, showed a LDH staining pattern resembling that of resting B lymphocytes, while lymphoblasts in T cell acute lymphoblastic leukaemia (T-ALL), high grade B cell lymphoma and Epstein-Barr virus (EBV) transformed cell lines showed a LDH staining pattern similar to that in activated T or B lymphocytes. Taken together, our results have demonstrated a significant correlation between expression of LDH and proliferative activity of cells. Immunostaining with the MoAbs to H- and M-type LDH can, therefore, provide a useful means not only for identification of T and B lymphocytes but also for rapid evaluation of the proliferating fraction of normal and neoplastic human cell populations. PMID- 1934593 TI - Raised serum levels of CD8, CD25 and beta 2-microglobulin in common variable immunodeficiency. AB - Soluble CD8, soluble CD4, soluble CD25 (IL-2 receptor), beta 2-microglobulin and the cytokine tumour necrosis factor-alpha (TNF-alpha) were measured in sera from patients with common variable immunodeficiency (CVI). Levels of soluble CD8, soluble CD25 and beta 2-microglobulin but not of soluble CD4 and TNF-alpha were raised significantly above levels in normal sera. Sera from patients with X linked agammaglobulinaemia, who are also antibody deficient, did not show this marked elevation. The raised levels of soluble CD8, soluble CD25 and beta 2 microglobulin in CVI, correlated with the extent of the defects in the B lymphocytes assessed in vitro, as well as with the clinical severity of the disease. The selective release of these molecules into sera may indicate that abnormal cellular activation occurs in most CVI patients. It is also possible that the raised levels of these soluble molecules play a part in the immunodeficiency. PMID- 1934594 TI - Cytokines in sera from insulin-dependent diabetic patients at diagnosis. AB - Cytokines are known to play an important role in autoimmunity and have been suggested to be involved in the pathogenesis of insulin-dependent diabetes (IDDM). In the present study we have measured IL-1, IL-2, IL-4, IL-6, interferon gamma (IFN-gamma) and tumour necrosis factor (TNF) (using both immunoassays and bioassays) in sera from 50 patients affected by IDDM at the time of clinical diagnosis and 51 age and sex matched controls. Detectable levels of IL-1, IL-2, IL-6 and IFN-gamma were found in the serum of a small percentage of subjects and were not significantly different between patients and controls. IL-4 was detectable in a higher number of both patients and controls and circulating TNF alpha (greater than 1 U/ml) was found in a percentage of patients (24%) significantly higher than controls (P less than 0.01). Raised levels of TNF-alpha were detectable using an immunoenzymatic assay whereas TNF bioactivity in these samples was negligible. We conclude that the presence of immunoreactive TNF-alpha in the patient's sera may reflect an increased localized production of this cytokine at pancreatic level. However, the measurement in serum of other cytokines does not add information on the role that they may play in the pathogenesis of IDDM. PMID- 1934595 TI - Immunoglobulin and antibody levels in bronchoalveolar lavage fluid from symptomatic and asymptomatic pigeon breeders. AB - Twenty-one symptomatic subjects with pigeon breeders' lung (PBL) and 10 asymptomatic pigeon breeders, with a similar exposure to pigeon antigens, underwent bronchoalveolar lavage. Total IgG, IgM and IgA in lavage fluid were determined as were specific antibody levels against antigens in pigeon serum and droppings. Results were converted to levels in epithelial lining fluid (ELF) using lavage and serum urea ratios. It was found that symptomatics represent a group that is hyperreactive to pigeon antigens compared with the asymptomatic group with significantly higher IgG, IgM, IgA levels as well as specific antibody levels against pigeon serum and droppings. Paired serum and ELF samples from 12 symptomatic subjects showed significantly elevated IgG, IgM and IgA levels in ELF compared with serum when values were expressed in terms of albumin. This strongly supports the concept of local production of immunoglobulins within the lung after inhaling immunogens as opposed to their diffusion from the vasculature. Results for IgA indicate that any putative protective role for this immunoglobulin is not valid in relation to the prevention of extrinsic allergic alveolitis. Analysis of smoking habits, lung immunoglobulins and response to inhalation challenge confirm the negative influence of smoking on total and functional lung immunoglobulins; however, levels in the ELF of ex-smokers suggest that the effect of smoking is not permanent. Smoking did not prevent responses to inhalation challenge. PMID- 1934596 TI - T cell response to purified filtrate antigen 85 from Mycobacterium bovis Bacilli Calmette-Guerin (BCG) in leprosy patients. AB - T cell proliferation and IFN-gamma production of peripheral blood mononuclear cells from 25 healthy controls and 39 leprosy patients were tested against BCG bacilli and culture filtrate. Mycobacterium leprae and purified antigen 85 (the major secreted 30-32 kD protein antigen) from M. bovis strain BCG. In lepromin negative healthy controls, blastogenesis was low to M. leprae and completely negative to antigen 85. IFN-gamma levels were very low, close to detection limits. In all lepromin positive controls, significant proliferation and IFN gamma secretion was found in response to M. leprae and antigen 85. In the group of lepromatous leprosy (LL) patients, 25/29 of patients (with either positive (13) or negative (12) lymphoproliferative response to BCG) were unreactive to M. leprae or to antigen 85. Four LL patients with positive T cell response to BCG responded with detectable lymphoproliferative response and IFN-gamma secretion to antigen 85. All tuberculoid (TT) leprosy patients responded to BCG, M. leprae and antigen 85. Hence, T cells from leprosy patients and controls demonstrate a marked parallelism of responsiveness towards whole M. leprae and purified antigen 85 from M. bovis BCG, suggesting strong cross-reactivity between the two species and underlining the biological importance of such secreted antigens. PMID- 1934597 TI - Actinomycin D upregulates lipopolysaccharide induction of macrophage procoagulant expression and tumour necrosis factor-alpha production. AB - The antitumour antibiotic actinomycin D (Act D) and the aminosugar D galactosamine both enhance the sensitivity of animals to bacterial lipopolysaccharide (LPS). Lipopolysaccharide stimulates macrophage membrane-bound procoagulant activity (MPCA) and tumour necrosis factor-alpha (TNF-alpha) production in vitro. We investigated the effects of LPS combined with either Act D or D-galactosamine on procoagulant and TNF-alpha production in vitro. Actinomycin D directly induced procoagulant on the malignant monocytoid cell line WEHI 265, and synergized with LPS to enhance MPCA on both WEHI 265 cells and thioglycollate-induced peritoneal exudate macrophages. In the presence of Act D, exudate macrophages expressed procoagulant in response to concentrations of LPS 100,000-fold lower than normally required. Pulsing experiments demonstrated that LPS primed these cells within 4 h to respond to Act D, whereas 4 h priming with Act D inhibited subsequent procoagulant induction by LPS. Although its effects on TNF-alpha production were less intense, low levels of Act D more than doubled TNF alpha produced by LPS-stimulated exudate macrophages. Procoagulant expression and TNF-alpha production were not always co-ordinately expressed; interferon-gamma (IFN-gamma) synergized with LPS to enhance both responses but when IFN-gamma was combined with Act D only procoagulant was upregulated. D-galactosamine failed to affect these macrophage responses. Results indicate different in vivo mechanisms of enhancement of LPS toxicity by these two agents. PMID- 1934598 TI - Inhibitory effect of 11 beta-hydroxypregna-1,4-diene-3,20-dione (delta HOP) on lymphocyte proliferation. AB - We have compared the immunosuppressive effect of delta HOP and glucocorticoids on lymphocyte proliferation and IL-1 secretion. The new synthetic steroid only inhibited proliferation of phytohaemagglutinin (PHA)-stimulated human lymphocyte at high concentrations and the effect did not persist after washing out the steroid. In contrast, glucocorticoids produced the classical dose-response inhibition and the effect persisted when they were removed from the cultured medium. Although both steroids decreased IL-1 secretion from human monocytes stimulated with lipopolysaccharide (LPS), they exert the same effect through a different mechanism. The experiments we report suggest that the decrease of IL-1 synthesis produced by delta HOP could be caused by inhibition of LPS phagocytosis. These results support our hypothesis that delta HOP exerts its immunosuppressive and anti-inflammatory effect by a non-genomic mechanism. PMID- 1934599 TI - Suppressive effect of hyperbaric oxygenation on immune responses of normal and autoimmune mice. AB - We studied the effect of hyperbaric oxygenation (HBO) on immune responses in normal and autoimmune mice. Mice were exposed to HBO in an animal chamber at a pressure of 252.5 kPa for 1 h and once a day for 5 days. The immunization of C3H/He mice with sheep erythrocytes induced marked anti-sheep erythrocyte antibody response on day 7. However, this response was markedly suppressed in HBO treated mice. The suppression is dependent on the duration of HBO and it works on the early and the late stage of antibody responses. HBO suppresses the development of both sheep erythrocyte-specific B cells and helper T cells after the immunization. Then, we tried to expose autoimmune mice to HBO. Spontaneous immunoglobulin production of NZB and MRL/lpr spleen cells was also significantly suppressed by HBO. Furthermore, long term HBO exposure results in the suppression of the development of autoimmune symptoms such as proteinuria, facial erythema and lymphadenopathy in MRL/lpr mice. All these results suggest that HBO is applicable for the treatment of autoimmune diseases. PMID- 1934600 TI - Kupffer cell depletion in vivo results in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells. AB - In the present study we have investigated the clearance kinetics and tissue distribution of monomeric (m) IgG and soluble aggregates of IgG (AIgG) and immune complexes (IC) in normal and Kupffer cell (KC) depleted rats. In normal rats, clearance of mIgG occurred in a biphasic manner with a first half-life (T1/2) (T1) of 36.3 +/- 6.3 min and a second T1/2 (T2) of 168.4 +/- 4.7 min. AIgG composed of 20-27 IgG molecules per aggregate were cleared significantly faster than mIgG with a T1 of 2.5 +/- 0.1 min and a T2 of 32.5 +/- 5.6 min. KC depletion did not have a significant effect on the clearance rate of mIgG (T1: 33.4 +/- 8.9 min; T2; 159.5 +/- 12.5 min), while clearance of AIgG was delayed significantly with T1 4.8 +/- 0.7 min and T2 41.2 +/- 3.2 min. Eight minutes after injection, 77% of AIgG was found in the liver in normal rats while 62% was found in the liver of KC-depleted rats. Double immunofluorescence studies indicated that AIgG in the liver was associated with KC and endothelial cells (EC) in normal rats. In KC-depleted rats, AIgG was strongly associated with EC. A similar staining pattern was observed when IgG-immune IC were administered. The clearance of AIgG in KC-depleted rats was inhibited fully by pre-administration of high concentrations of IgG but not by pretreatment with IgA. asialofetuin (ASFe) or ovalbumin (OVA). Aggregated F(ab')2IgG was cleared with a comparable rate to mIgG from the circulation, again suggesting Fc gamma receptor-mediated elimination of AIgG by EC. There was a reduced degradation of AIgG in rats depleted of KC as compared with normal rats. These data suggest binding and degradation of AIgG by EC in vivo. PMID- 1934601 TI - Ontogenesis of the secretory immune system and innate defence factors in human parotid glands. AB - Immunoglobulin-producing cells and epithelial expression of secretory component (SC), amylase, lysozyme (Ly) and lactoferrin (Lf) were studied by immunohistochemistry to obtain information about the development of mucosal immunity. Tissue specimens were obtained from 20 fetal and 40 postnatal parotid glands. (1) Fetal specimens. Occasional IgM- and IgA- but no IgD-, IgG- or IgE- producing cells were seen (ratios, IgM:IgA:IgD:IgG:IgE approximately 4:1:0:0:0). The IgAl subclass dominated (median 90%, range 50-95%) and these cells were mostly J-chain-positive (median 97%, range 94-98%). Only few IgA2-producing cells were seen (median 10%, range 5-50%) and they were also mostly J-chain-positive (median 99%, range 98-100%). Amylase, Ly and Lf were most prominent in early fetal life, while only small amounts of SC were present. (2) Postnatal specimens. Secretory component increased markedly along with a growing number of IgA- and IgD-producing cells (IgA:IgM:IgD:IgG:IgE approximately 4:2:1:1:0). The IgAl subclass remained predominant (median 65%, range 50-90%) although the proportion of IgA2-positive cells tended to be raised (median 35%, range 10-50%). Most IgAl (median 97%, range 67-100%) and IgA2 (median 94%, range 75-100%) cells were J chain-positive. These features probably reflected local activation of the immune system in response to environmental factors. The amount of amylase, Ly and Lf decreased shortly after delivery, perhaps because the cellular stores were emptied by postnatal increase in secretory activity. PMID- 1934602 TI - Complement activation and bioincompatibility. The terminal complement complex for evaluation and surface modification with heparin for improvement of biomaterials. AB - The degree of biocompatibility of biomaterials can be evaluated using various assay systems detecting activation of the blood cascade systems, leukocytes or platelets. Activation of complement is one mechanism associated with adverse effects observed when bioincompatible materials are used. We present data showing that the terminal complement complex, an indicator of terminal pathway activation, is suitable for evaluation of biocompatibility of biomaterials such as cardiopulmonary bypass devices. Furthermore, our results suggest that bioincompatibility is improved when artificial surfaces are modified with end point attached functionally active heparin. PMID- 1934603 TI - Complement evasion by parasites: search for "Achilles' heel". PMID- 1934605 TI - Complement deficiencies and meningococcal disease. PMID- 1934604 TI - Deficiency of mannan binding protein--a new complement deficiency syndrome. PMID- 1934606 TI - The ionic and biochemical basis for T-cell activation and proliferation. Potential causes of impaired T-cell function. AB - The binding of mitogens to cells of different lineages triggers a series of ionic and biochemical events that are thought to be important for cell differentiation and growth. Lymphocytes share many of these pathways but may be deprived of others. Changes in cytosolic Ca2+ levels are pivotal in receptor-initiated signal transduction, especially for signaling IL2 gene transcription and IL2 synthesis/secretion. Antigen-presenting cells play a major role in triggering this Ca2+ response of T cells. The major component of the Ca2+ response appears to be transmembrane Ca2+ uptake, presumably through Ca2+ channels. Such ligand gated Ca2+ channels are regulated differently from the Ca2+ channels of excitable cells. In addition to increases in Ca2+, there are other ion fluxes and biochemical events which are observed following ligand binding to specific receptors. Many of these events appear to be the consequence of cell activation but do not appear to be essential for the T-cell proliferative response. Further characterization of these pathways may explain the T-cell immunodeficiencies which appear in the presence of phenotypically normal T cells in the periphery. PMID- 1934607 TI - Interferon-gamma in the treatment of the chronic granulomatous diseases of childhood. AB - The bactericidal activity of phagocytic cells depends largely on the production of highly reactive metabolites from the metabolism of oxygen. A lesion anywhere in the biochemical pathway of hydrogen peroxide production has the potential to cause chronic granulomatous disease (CGD). Recent findings have shown that CGD results from distinct abnormalities in the NADPH oxidase system, which includes the membrane-associated proteins, NADPH oxidase, cytochrome b-558, and several cytosolic proteins. Specific genetic markers have been identified for the most common biochemical variants of CGD. Pharmacologic alteration of phagocyte oxidative metabolism is now possible through the use of recombinant interferon gamma. In vitro studies have shown that neutrophils and monocytes derived from patients with autosomal recessive cytochrome b-positive CGD respond to interferon gamma with an enhanced respiratory burst (superoxide production) and increased bactericidal activity. Furthermore, subcutaneous interferon-gamma administration improves bactericidal activity in neutrophils and monocytes derived from patients with X-linked, cytochrome b-negative CGD, despite the lack of effect on superoxide production. This suggests that interferon-gamma also stimulates nonoxidative bactericidal pathways. Data from a multicenter clinical trial indicate sustained administration of interferon-gamma is effective in the management of CGD. In addition, related studies indicate that modern molecular and genetic technologies offer the possibility of improved management or cure for CGD. PMID- 1934608 TI - Combined immunodeficiency with defective expression in major histocompatibility complex class II genes. AB - There are many examples of inherited immunodeficiencies characterized by normal differentiation of T and B lymphocytes but abnormal functions of these cells. Among them, combined immunodeficiency with defective expression in MHC class II genes was the first to be individualized. It is called MHC class deficient SCID by the WHO committee for the classification of immunodeficiency. It is an autosomal recessive disease with a severe evolution. Most of the 30 patients described died unless they were transplanted with HLA identical or HLA mismatched bone marrow. All HLA class II molecules (DR, DQ, and DP specificities) are absent on the cell surface in all tissues while HLA class I molecules are detectable. T and B cell abnormalities are characterized by defective in vivo and in vitro responses to antigens, although in vitro reactivity to mitogens is normal. These anomalies are considered as a direct consequence of the absence of HLA class II molecules on the surface of antigen-presenting cells incapable of sensitizing T cells. It was strongly suggested that MHC class II deficient SCID is due to a mutation that affects the regulation of the expression of all genes involved in the synthesis of MHC class II molecules. PMID- 1934609 TI - Novel immune deficiencies: defective transcription of lymphokine genes. AB - A 4-year-old female with severe combined immunodeficiency (SCID) had normal numbers of T cells in circulation and normal T cell subsets. However, her T cells proliferated poorly to mitogens and did not proliferate to antigens or to anti CD3 mAb. Interleukin-2 (IL-2) receptor expression was normal but IL-2 synthesis was undetectable. The addition of recombinant IL-2 to a mitogen-stimulated culture resulted in normalization of the proliferative response. Northern blot analysis of total RNA derived from the patient's T cells revealed a weak or absent expression of mRNA coding for IL-2, IL-3, IL-4, and IL-5. In contrast, there were normal amounts of mRNA coding for granulocyte-macrophage colony stimulating factor (GM-CSF). Tumor necrosis factor and IL-6 production was also normal. Nuclear run on transcriptional assays revealed markedly decreased levels of newly initiated nuclear transcripts coding for IL-2, IL-3, IL-4, and IL-5 and normal levels of GM-CSF transcripts in patient relative to control lymphocytes. These results indicate that the patient's T cells suffered from a defect affecting the transcription of multiple T cell lymphokines and suggest that abnormalities affecting the production of T cell lymphokines may underlie some of the primary immunodeficiency diseases. PMID- 1934610 TI - Substituted guanine ribonucleosides as B cell activators. AB - Monosubstituted (at C8) and disubstituted (at C8 and N7) guanine ribonucleosides activate human and murine B lymphocytes. A newly developed disubstituted analog, 7-allyl 8-oxoguanosine (7ally18oGuo), in a dose-dependent manner induced anti tetanus-specific IgG antibody response in peripheral blood mononuclear cells in humans. In addition, 7ally18oGuo activated monocytes from healthy subjects and patients with common variable immunodeficiency to produce interleukin 1. Furthermore, 7ally18oGuo induced changes in plasma membrane potentials and intracellular pH in human peripheral blood mononuclear cells. The role of monosubstituted and disubstituted compounds in restoring immunodeficient states in mice and humans, both in vivo and in vitro, is reviewed. PMID- 1934612 TI - Lymphokine receptor-directed therapy: a model for immune intervention in leukemia, autoimmunity, and immunodeficiency. AB - Activation of resting T cells induces the synthesis of interleukin-2 (IL-2) and expression of its high-affinity receptor that involves both a 55-kDa IL-2 binding peptide identified by the anti-Tac monoclonal antibody and a 75-kDa IL-2 binding peptide associated in a receptor complex. The IL-2 receptor is proving to be an extraordinarily important therapeutic target since it is expressed by the abnormal T cells in patients with certain lymphoid malignancies or autoimmune disorders and in individuals rejecting allografts whereas it is not expressed by normal resting cells. IL-2 receptor directed monoclonal antibodies, genetically engineered humanized antibodies, and antibodies armed with toxins or radionuclides represent novel therapeutic agents for these clinical conditions. PMID- 1934611 TI - Cytokines regulating human B cell growth and differentiation. AB - Utilizing a model system of anti-CD3-stimulated T cells, we have identified a potent B cell differentiation factor (BCDF) in the supernatant of these cells. This factor, 446-BCDF, appears to act on SAC-activated B cells inducing a 10- to 100-fold increase in Ig secretion. 446-BCDF has an apparent MW of 32 kDa and a pI of 6.0. Its activity cannot be inhibited by an anti-IL-6 antiserum, and activity is enhanced after passage over an anti-IL-6 affinity column. 446-BCDF activity is detected in the 50 mM salt fraction eluted from a Mono Q column. This 50 mM fraction has the only activity detected after passage over an anti-IL-6 affinity column and migrates with an apparent pI of 6.0. Taken together these data suggest that 446-BCDF is a unique potent polyclonal human BCDF which may be a predominant factor regulating terminal B cell differentiation. PMID- 1934613 TI - Progress toward gene therapy. AB - The prospect of treating human disease at its most fundamental (i.e., genetic) level has been the dream of clinicians for decades. There are over 4000 distinct genetic diseases, many of which are debilitating or fatal and most of which are incurable by standard medical approaches. Initial research was directed toward gene replacement treatment of genetic diseases involving the bone marrow, such as sickle cell anemia. Efficient methods for gene transfer were developed, but as this research progressed it became apparent that the biology of the bone marrow stem cell and the regulation of hemoglobin synthesis were not understood well enough to realistically permit an attempt at gene therapy for these diseases. These difficulties spurred research on alternative approaches which has unexpectedly led to the development of techniques to use gene therapy for the treatment of both rare genetic disorders as well as more common "nongenetic" diseases such as cancer. Our research has focused on one of the most promising cellular alternatives to the bone marrow stem cell, the T lymphocyte. This paper summarizes the historical background and evolution of thinking which led to the initial clinical applications of gene transfer and gene therapy in man. PMID- 1934614 TI - Selective IgA deficiency, IgG subclass deficiency, and the major histocompatibility complex. AB - Here we have examined the connection between IgA deficiency, IgG subclass deficiency, and the absence of alleles of complement C4, and show that IgA deficient subjects who have IgG subclass deficiencies may also have an increased frequency of C4 null alleles. In our group, we found an increased incidence of HLA B38 which might reflect the ethnic composition of the patients tested. While family studies are of primary importance to assess the relationships between histocompatibility antigens and immune deficiency, these studies are complicated by the observation that C4 null alleles are not always inherited with the humoral defect. PMID- 1934616 TI - Genetic defects of the complement system. PMID- 1934615 TI - IgG subclass deficiency with or without IgA deficiency. AB - IgG subclass deficiency (IgGSD) is difficult to define since reference materials vary between laboratories and the clinically relevant cut off levels for the various subclasses are not well known. The diagnosis of IgGSD should be based on more than one determination since the levels vary, due to various factors such as infections, operations, etc. There is a relation between IgGSD and occurrence of frequent infections, but at the same time even total lack of a subclass can be seen in healthy individuals. Infections in the upper and lower respiratory tract predominate. Gm allotypes influence IgG subclass levels. Most IgGSD patients are homozygous in the Gm system. Immunocytes producing IgG3 in the nasal mucosa correlate with serum IgG3 levels, whereas rectal IgG1 producing cells relate to serum IgG1 levels. This may reflect differences in antigen and/or mitogen exposure at the two mucosal sites. IgG2SD is the predominant form of IgGSD among children, whereas after puberty IgG3SD is most common. At the same age period there is a switch in sex distribution from three boys/one girl to one male/three females. Various abnormalities in B and T lymphocyte numbers and function are often found. In a double blind crossover study of Ig prophylaxis over 2 years in 43 IgGSD adult patients a significant decrease in the number of days with infections was seen both in the whole group and among the IgG1 deficient. Days with bronchial constriction were also significantly decreased among the 22 patients who had asthma as well. Acute bronchitis became significantly less frequent in the IgG3 deficient patients during Ig prophylaxis. This was seen in those under the lower range of 0.41 g/liter of Oxelius' early normal material, although many recent reference materials suggest 0.14-0.15 g/liter of IgG3 as the cut off. In a group of 25 consecutive patients with IgGSD + IgA deficiency recurrent respiratory infections were the major problem and lung function impairment was found in 12, and bronchiectasies in 5. Still many individuals with this combined deficiency have been reported to be healthy, again illustrating our limited understanding of these conditions. PMID- 1934617 TI - X-linked agammaglobulinemia. AB - X-linked agammaglobulinemia (XLA) patients manifest a very low production of immunoglobulins (Ig) of all classes and plasma cells are virtually absent. The XLA gene plays a crucial role in the transition of pre-B cells to later B cell stages, as hardly any slg-positive B lymphocytes can be detected. In the bone marrow almost normal numbers of pre-B lymphocytes are present. These cytoplasmatic C mu+ pre-B lymphocytes appear to express truncated M heavy chain molecules lacking the variable region segment. The T lymphocyte compartment is intact: the numbers of mature T cell receptor (TcR) alpha beta expressing T lymphocyte populations and their proliferative responses to antigens are normal. That the B cells are primary and exclusively affected was proven by X-chromosome inactivation studies. There is no evidence that the XLA gene is directly involved in the Ig gene rearrangements since B lymphoblastoid cell lines (BLCLs) established from peripheral blood of XLA patients were found to produce IgM molecules composed of complete Ig heavy and light chains and were shown to contain normal VHDJH recombinations. The data do not exclude the involvement of the XLA gene in a B cell specific process that makes the Ig loci accessible for recombination. Investigations on the degree of diversity of immunoglobulins generated by XLA patients exposed no limitations in the VH family usage. Sequence analysis of expressed VH3 and VH4 rearrangements however revealed that some genetic elements of the Ig locus might be over-represented and that a high portion of rearrangements was generated by unconventional mechanisms. By restriction length polymorphism (RFLP) and pulsed field gel electrophoreses analyses the XLA gene was mapped to an 8- to 12-Mb DNA fragment located in the Xq22 region. The known location of the XLA gene on the X-chromosome with closely linked RFLP markers and the availability of X-chromosome inactivation assays provides methods for carrier detection and prenatal diagnosis. PMID- 1934618 TI - X-linked severe combined immunodeficiency. AB - Between a third and half of all males with SCID and no family history of immunodeficiency represent the first manifestation in their family of a new mutation of the gene that causes X-linked SCID. These patients, like boys with a positive family history of X-linked SCID, have markedly reduced numbers of T cells, elevated numbers of B cells, and hypogammaglobulinemia. The hypogammaglobulinemia is due, at least in part, to the expression of the gene defect in B cells as well as in T cells. Patients with X-linked SCID who are treated with bone marrow transplant tend to engraft T cells readily but they do not engraft B cells unless they are treated with cytoreductive therapy prior to transplant. B-cell function after transplant tends to be poor, even in patients who have received transplants from HLA matched siblings. Better transplant strategies are required to achieve optimum long-term results in patients with X linked SCID. PMID- 1934619 TI - Cytokines and autoimmune disease. AB - A wide array of cytokines are locally present in autoimmune lesions where they are produced by inflammatory cells or by the target cell of the autoimmune attack. The presence of cytokines at the site of autoaggression reflects ongoing inflammatory and activation processes. These mediators exert proinflammatory effects, contribute to the activation and stimulation of the effector function of T or B lymphocytes, directly participate in target cell destruction, and mediate accompanying local reactions, including fibrotic processes. The release of cytokines into the circulation may explain certain systemic reactions, including fever or changes in the profile of plasma proteins. Many, especially systemic, autoimmune diseases are accompanied by a dysregulation of lymphokine secretion at the level of circulating leukocytes or cells situated outside of the local inflammatory event, thus reflecting regulatory disorders that may either have a genetic or an acquired basis. Decreased production of lymphokines in vitro in response to nonspecific stimuli may be accompanied by an elevated spontaneous release in vivo resulting in an increase of circulating cytokine levels (interleukin 2, tumor necrosis factor-alpha). Secretion of interleukin 1, interleukin 2, and tumor necrosis factors-alpha or -beta, in part, is determined by genetic factors and it is possible that a particular secretor phenotype may predispose to the development of autoimmune lesions. Probably due to their pleiotropic nature, systemic administration of cytokines such as interleukin 1, interleukin 2, tumor necrosis factor, and interferon-gamma may exert either accelerating or suppressive effects on autoimmune diseases. Conversely, agents that block the function of the lymphokine interleukin 2 exert an unequivocal autoimmune disease-inhibiting effect. PMID- 1934620 TI - Composition of immune deposits present in glomeruli of NZB/W F1 mice. AB - This paper describes the results of experiments designed to investigate the composition of immune complexes present, in the form of immune deposits, in glomeruli of NZB/NZW F1 mice. Granular deposits of mouse IgG were present along the glomerular capillary walls of 6- to 12-month-old mice. Disappearance of mouse IgG from glomerular deposits, indicating a dissociation of immune complexes, was observed following incubation of kidney sections with an excess of mouse IgG, mouse Fc fragments, rat IgG, and rat Fc fragments, but not with human and rabbit Cohn fraction-II (FII), DNA, nucleohistone, and PBS. Antinuclear antibody activity in mouse sera or in glomerular eluates was removed by absorption with mouse IgG or mouse Fc fragments, rat IgG or rat Fc fragments, DNA, and nucleo histone, but not by absorption with human or rabbit FII. These results suggest that the IgG antinuclear antibodies present in the sera and in glomerular deposits possess rheumatoid factor (RF) activity. In other experiments, kidney sections were incubated with various concentrations of pepsin, which digests the Fc portion of the IgG. After digestion, the sections were washed and stained for mouse IgG, IgG F(ab')2, and IgG Fc. At concentration of 10 micrograms/ml, pepsin completely removed IgG and IgG Fc, whereas faint IgG F(ab')2 deposits persisted in glomerular deposits. At the concentration of 1 microgram/ml, deposits of mouse IgG, F(ab')2, and Fc persisted, while F(ab')2 was observed bound to nuclei of glomerular cells. At the pepsin concentration of 0.1 microgram/ml or 0.01 microgram/ml, IgG F(ab')2 was bound to the nuclei of glomerular and tubular cells, indicating that the digestion of the Fc portion of IgG had released F(ab')2 with nuclear reactivity from glomerular deposits. The solubilization of mouse IgG from glomerular immune deposits with mouse IgG and the demonstration that pepsin digestion releases mouse F(ab')2 with nuclear reactivity are consistent with the interpretation that the immune deposits present in glomeruli of NZB/NZW F1 mice contain complexes formed by antinuclear IgG and IgG RF. These two antibodies probably cross-react and form multilayer aggregates which contribute to the formation of immune deposits. PMID- 1934621 TI - Progressive glomerular injury after recovery from acute glomerulonephritis in rats. AB - To determine if an acute immunologic injury resembling poststreptococcal nephritis could lead to chronic renal injury, rats with immune-complex glomerulonephritis produced with cationic human gammaglobulin were followed for 48 weeks. During Week 1, animals developed severe proteinuria, hypoalbuminemia, and a diffuse proliferative/exudative glomerulitis. Substantial recovery, characterized by a significant decline in urinary protein excretion and normalization of plasma albumin concentration, occurred by Week 4. Subsequently, rats developed significantly elevated blood pressures and increasing proteinuria. Glomerular histology at Week 48 revealed minimal inflammation, significant hypertrophy, and considerable sclerosis. We conclude that chronic, progressive renal disease can evolve after apparent recovery from an acute immunologic insult. Further study of this model should provide clinically relevant information about the mechanisms underlying this process. PMID- 1934622 TI - Idiotypic and immunochemical differences of anti-DNA antibodies of a lupus patient during active and inactive disease. AB - IgG anti-DNA antibodies of a lupus patient during active and inactive stages of her disease were studied. There were no significant differences in the amounts, in double-stranded DNA-binding activity, or in complement-fixing ability between purified IgG anti-DNA antibodies of both stages. However, their idiotype (Id) expressions were different as revealed by binding to rabbit anti-Ids raised against each of the anti-DNA antibodies. Moreover, the active stage anti-DNA antibodies had higher activity and less cross-reactivity with polynucleotides. Dominant anti-DNA populations during the active and inactive stages of systemic lupus erythematosus are clonally and qualitatively different. PMID- 1934623 TI - Response of huSCID mice reconstituted with lymphocytes from anti-idiotype-treated melanoma patients. AB - Severe combined immune deficient (SCID) mice were reconstituted with peripheral blood mononuclear cells (PBMC) from normal and melanoma patients. The melanoma patients were part of a clinical trial of active immunotherapy with the murine monoclonal anti-idiotypic antibody, IMelpgl. IMelpgl represents an idiotypic mimic of the high-molecular-weight melanoma-associated antigen, HMW-MAA. All of the huSCID mice reconstituted fully as evidenced by their production of human immunoglobulins. Furthermore, approximately half of the huSCID mice reconstituted with PBMC from either normal or melanoma patients were able to mount a secondary response to tetanus toxoid. While all of the huSCID mice reconstituted with PBMC from patients undergoing immunotherapy produced strong HAMA responses, only one huSCID mouse responded idiotypically to IMelpgl immunization. These results demonstrate tht the huSCID mouse can be used as an experimental model to monitor and study the response of human B cells derived from patients undergoing active immunotherapy. PMID- 1934624 TI - Cytokine secretion by peripheral blood monocytes from human immunodeficiency virus-infected patients is normal. AB - We have measured the production of interleukin 1 (IL 1), interleukin 6 (IL 6), and tumor necrosis factor alpha (TNF alpha) by unstimulated monocytes and monocytes stimulated with lipopolysaccharide (LPS) isolated from the peripheral blood of patients infected with human immunodeficiency virus 1 (HIV-1) and healthy controls. Spontaneous and LPS-induced cytokine production were not significantly different between patients and controls. Median lipopolysaccharide stimulated cytokine secretion for patients and controls was 1.7 and 4.3 U/ml for IL 1, 475 and 625 U/ml for IL 6, and 468 and 580 pg/ml for TNF alpha. Cytokine levels were not related to stage of disease. We conclude that in vivo HIV infection itself does not alter peripheral blood monocyte cytokine secretion. PMID- 1934625 TI - Influence of IgG1 and IgG2 antibodies to streptococcal group A carbohydrate on neutrophil chemiluminescence. AB - IgG antibodies to streptococcal group A carbohydrate (A-CHO) were isolated from normal human serum and from pooled Cohn fraction II using N-acetyl-D-glucosamine affinity chromatography columns. They consisted of the subclasses IgG1 and IgG2 in variable proportions depending on the pH of the elution buffer and on the subclass composition of anti-A-CHO in the starting material. Streptococcal group A particles exposing the antigen A-CHO were opsonized with various concentrations of these antibodies and incubated with normal human polymorphonuclear leukocytes (PMN). The luminol-enhanced chemiluminescence (CL) elicited with these particles was recorded over a 60-min period. With 12 of the 14 antibody preparations tested, the observed CL signal was dose-dependent. When used at comparable concentrations for opsonization, the antibodies enriched in IgG1 induced markedly stronger CL signals than those consisting predominantly of IgG2. It was concluded that the observed CL differences reflect mainly the preferential recognition of IgG1 molecules by Fc gamma receptors of PMN. PMID- 1934626 TI - The anti Mac-1 monoclonal antibody inhibits neutrophil sequestration in lung and liver in a septic murine model. AB - We investigated the mechanism by which leukocytes adhere to the pulmonary and liver microvascular endothelium in a septic murine model. After C57BL/6 mice were intraperitoneally (ip) injected with lipopolysaccharide (LPS), a striking peripheral leukocytopenia occurred as neutrophils accumulated rapidly in the lung and liver. When the anti-Mac-1 monoclonal antibody (mAb) was administered intravenously (iv) 2 hr before the ip administrated LPS, leukocytopenia and neutrophil accumulation in the lung and liver were inhibited significantly at 3 hr after the LPS injection. An immunofluorescence study revealed that Mac-1 expression on leukocytes from LPS-injected mice were greatly increased when compared to that of controls. Additionally, an in vitro assay demonstrated that LPS-activated serum increased neutrophil Mac-1 expression and neutrophil adhesion to the endothelial monolayer and that these phenomena are inhibited by pretreatment of neutrophils with anti-Mac-1 mAb. These results indicate that a marked increase in Mac-1 antigen expression by leukocytes plays a crucial role in striking neutrophil attachment to the vascular endothelium and is likely to be the cause of neutrophil accumulation in the lung and liver during endotoxemia. PMID- 1934627 TI - Sequential changes in lung injury induced by preformed immune complexes. AB - Immune complexes formed in the airside may be involved in the early parenchymal changes in hypersensitivity pneumonitis. The present study was undertaken to compare the responses of animals after an intratracheal injection with preformed immune complexes to those of patients with acute hypersensitivity pneumonitis, with special emphasis on sequential bronchoalveolar lavage findings and the possible role of chemotactic factors in the immune complex-induced lung injury. An increased number and percentage of polymorphonuclear cells could be detected in bronchoalveolar lavage fluids of guinea pigs within 48 hr following an intratracheal injection of preformed immune complexes. Chemotactic factor activity preceded the observed increase of polymorphonuclear cells in bronchoalveolar lavage fluids, suggesting a role for chemotactic factors in the sequestration of these cells in the lung. In addition, this study confirmed the usefulness of bronchoalveolar lavage in evaluating the pulmonary findings because the changes in bronchoalveolar lavage cell populations correlated with sequential histological findings. The sequential characteristics of the involved areas were noted to be of a peribronchial or bronchiolar infiltration with polymorphonuclear cells at early stages, then alveolar sac infiltration, followed by mild infiltration of mononuclear cells into the alveolar walls. The findings suggest a possible role for chemotactic factors in the accumulation of polymorphonuclear cells, and the sequential changes of bronchoalveolar lavage and histological findings in animals are comparable to those in patients with acute hypersensitivity pneumonitis. PMID- 1934628 TI - MHC II-restricted, CD4+ cytotoxic T lymphocytes specific for herpes simplex virus 1: implications for the development of herpetic stromal keratitis in mice. AB - Herpetic stromal keratitis (HSK) appears to represent an immunopathological reaction in which CD4+ T cells play a prominent role. However, the exact immunopathological mechanism(s) utilized by CD4+ T cells during HSK remains to be elucidated. In this study, the presence of cytotoxic CD4+ T lymphocytes in the cervical and retropharyngeal lymph nodes of Balb/c mice experiencing HSK was investigated. After in vitro depletion of CD4+ or CD8+ T cells with specific monoclonal antibodies and complement treatment, the cytotoxic functions of the remaining T cell populations were assayed by using target cells expressing either MHC Class I or both Class I and Class II. Our results showed the presence of a distinct cytotoxic T lymphocyte (CTL) population which was CD4+ and demonstrated lytic activity in a Class II-restricted fashion. Furthermore, these cells were able to develop into efficient effector CTL in the absence of CD8+ T lymphocytes as assessed by in vivo depletion experiments. Immunohistochemical methods were also utilized to show the presence of both CD4+ lymphocytes and I-A+ cells in the corneal tissues during HSK. These findings support the notion that direct lysis of infected Class II-bearing corneal cells by CD4+ CTL might be one of the mechanisms leading to stromal immunopathology in herpetic infections. PMID- 1934629 TI - In vitro IgE production by interleukin 4-stimulated human peripheral blood mononuclear cells is suppressed by rapamycin. AB - Rapamycin (RAPA) is a new immunosuppressant which is 50-fold to 100-fold more potent than cyclosporin A (CyA) in inhibiting cellular immune responses and allograft rejection in animal models of organ transplantation. The drug's effect on in vitro IgE synthesis by interleukin (IL)4-stimulated human peripheral blood mononuclear cells was examined and compared with CyA's effect in this study. RAPA was found to be about 100-fold more potent than CyA in inhibiting IgE synthesis. Its inhibitory effect on IgE production was significant if it was added to the culture before Day 6 of a 14-day culture. The suppression was accompanied by the inhibitory effect on cell proliferation and on IgE-binding factor (IgE-BF) production. IL2 was able to partially reverse CyA- but not RAPA-induced inhibition of IgE production. Commercial B cell growth factor (cBCGF) was not able to reverse either RAPA- or CyA-induced suppression of IgE synthesis. The strong inhibitory effect of RAPA in IgE synthesis may be useful in certain clinical applications where overproduction of pathogenic IgE is a key issue. RAPA can also be used as a tool to dissect the regulation of IgE production. PMID- 1934630 TI - Long-term anti-CD4 treatment of MRL/lpr mice ameliorates immunopathology and lymphoproliferation but fails to suppress rheumatoid factor production. AB - MRL/lpr mice were treated with anti-CD4 mAb to define the role of CD4+ T cells in the pathogenesis of autoimmune disease and the lymphoproliferation characteristic of the strain. Anti-CD4 treatment was not associated with adverse effects, and survival of treated mice was increased over that of rat IgG-treated controls. Renal function was preserved, and the histologic severity of glomerulonephritis was minimal in treated mice. Lymphoid tissues of mice receiving anti-CD4 were effectively depleted of CD4+ T cells, and lymphoproliferation was markedly reduced. Serum IgG, anti-Sm, and anti-dsDNA levels were reduced significantly, while serum IgM and IgM rheumatoid factor levels were unaffected by anti-CD4 treatment. These data show that in MRL/lpr mice lymphoproliferation, renal disease, anti-Sm and anti-dsDNA antibody production, and elevated IgG levels are all linked to CD4+ T cell function. In contrast, both total IgM and IgM rheumatoid factor production appear to be the result of B-cell activity that is not regulated by CD4+ T cells. PMID- 1934631 TI - T lymphocyte migration to arthritic joints and dermal inflammation in the rat: differing migration patterns and the involvement of VLA-4. AB - The migration of T lymphocytes into arthritic joints of rats with adjuvant arthritis was examined and compared to the accumulation of the same cells in cutaneous inflammation, since previous studies had shown that only a subpopulation of T lymphocytes, found enriched in peritoneal exudates (sPEL), migrated efficiently to cutaneous inflammatory sites. Surprisingly, lymphocyte migration to the inflamed joint included T cells from most of the recirculating lymphocyte pool, including sPEL, spleen, peripheral lymph node (PLN), and Peyer's patches, and was much more rapid than migration through either cutaneous sites or PLNs. Treatment of sPEL with antibody to VLA-4 inhibited sPEL accumulation in the joints, while anti-VLA-4 treatment did not affect the accumulation of PLN T cells. It is concluded that the arthritic joint not only attracts inflammation seeking lymphocytes (sPEL), through at least a partially VLA-4 dependent interaction, but also large numbers of lymphocytes which normally migrate to PLNs through a VLA-4-independent mechanism. PMID- 1934633 TI - Cellular morphogenesis in the Saccharomyces cerevisiae cell cycle: localization of the CDC11 gene product and the timing of events at the budding site. AB - The Saccharomyces cerevisiae CDC3, CDC10, CDC11, and CDC12 genes encode a family of homologous proteins that are not closely related to other known proteins [Haarer BK, Ketcham SR, Ford SK, Ashcroft DJ, and Pringle JR (submitted)]. Temperature-sensitive mutants defective in any of these four genes display essentially identical pleiotropic phenotypes that include abnormal cell-wall deposition and bud growth, an inability to complete cytokinesis, and a failure to form the ring of 10 nm filaments that normally lies directly subjacent to the plasma membrane in the neck region of budding cells. We showed previously that the CDC3 and CDC12 gene products localize to the region of the mother-bud neck and are probably constituents of the ring of 10 nm filaments. We now report the generation of polyclonal antibodies specific for the CDC11 product (Cdc11p) and the use of these antibodies in immunofluorescence experiments with wild-type and mutant cells. The results suggest that Cdc11p is also a constituent of the filament ring, and thus support the hypothesis that the S. cerevisiae 10 nm filaments represent a novel type of eukaryotic cytoskeletal element. Cdc11p and actin both localize to the budding site well in advance of bud emergence and at approximately the same time, and both proteins also remain localized at the old budding site for some time after cytokinesis. Cdc11p also localizes to regions of cell-wall reorganization in mating cells and in cells responding to purified mating pheromone. Surprisingly, most preparations of affinity purified Cdc11p specific antibodies also stained the nuclear and cytoplasmic microtubules. Although this staining probably reflects the existence of an epitope shared by Cdc11p and some microtubule-associated protein, the possibility that a fraction of the Cdc11p is associated with the microtubules could not be eliminated. PMID- 1934634 TI - [Bonefit implant: an example of Swiss precision. Response to the maximum indications with the minimum of instruments]. PMID- 1934635 TI - [Hypnosis in dentistry]. PMID- 1934632 TI - Changes of soluble interleukin-2, interleukin-2 receptor, T8 antigen, and interleukin-1 in the serum of autistic children. AB - Immune abnormalities in autistic children led us to study for indirect evidence of immune activation as measured by the serum analysis of soluble interleukin-2 (sIL-2), interleukin-2 receptor (sIL-2R), T8 antigen (sT8), and interleukin-1 (sIL-1). The serum concentration of these soluble antigens was quantitated by enzyme-linked immunosorbent assays. The concentration of sIL-2 and sT8, but not of sIL-2R and sIL-1, antigens was significantly (P less than 0.05) increased in the sera of autistic children over that in the control healthy children or children with mental retardation (non-Down's syndrome). This finding indirectly indicates that the activation of a subpopulation of T cells occurs in some children with autism. PMID- 1934637 TI - Melanoma/skin cancer update 1991. PMID- 1934636 TI - Epidemiology of cutaneous melanoma. An update. AB - Dramatic increases in melanoma incidence and more moderate increases in the death rate have been observed. Although paradoxes exist, most, but not all, melanomas appear to be related in some way to solar exposure and genetic factors. No other exogenous factor has been strongly implicated. PMID- 1934638 TI - Factors influencing survival in melanoma. AB - Multiple factors appear to influence survival of patients with MM. As computer and mathematic analysis techniques advance, the specific effects of these variables, in terms of their impact on survival rates, will be delineated better. PMID- 1934639 TI - Volume of malignant melanoma is superior to thickness as a prognostic indicator. Preliminary observation. AB - There are many clinical and histologic factors that are known to be valuable in predicting survival rates for patients with cutaneous malignant melanomas. Breslow thickness is considered to be the most reliable prognostic factor; however, thickness is a unidimensional measurement. A more accurate mensuration to predict biologic behavior might be one that takes into account the three dimensional volume of the neoplasm. In a study of 35 primary malignant melanomas, the volumes of the dermal components of the tumors were calculated. Those patients with tumor volumes of 200 mm3 or less had a 91.4% 5-year disease-free survival rate, compared with survival rate of only 16.7% for those patients whose lesions had tumor volumes exceeding 200 mm3. On multivariate analysis, tumor volume exceeded thickness as a prognostic indicator. Thus, measurement of tumor volume proved to be of greater significance than thickness in predicting the outcome for patients with malignant melanomas. PMID- 1934640 TI - Surgical management of stage I malignant melanoma. AB - In part because of the increased public awareness regarding skin cancer, patients are presenting to their physician with thinner melanomas. Many lesions are now found in the in situ phase. The vast majority of melanomas referred to or diagnosed in the Skin Oncology Program at Boston University are less than 2 mm in thickness. In the increasingly uncommon situation of thicker lesions, the standard 3-cm margin excision continues to be performed until clinical trials indicate that lesser margins are safe. Definitive surgery is only part of the physician's responsibility in caring for the patient with melanoma. These patients need to be followed up on a regular basis for life, because of the long latent period for risk of metastasis and to facilitate early detection of new primary melanomas. PMID- 1934641 TI - Changing trends in melanoma treatment and the expanding role of the dermatologist. AB - As the incidence of melanoma continues to increase, so does the role of the dermatologist as both medical and surgical oncologist for these patients, especially those with stage I disease. The dermatologist holds a key role in all phases of care, including prevention, diagnosis, treatment, and follow-up. The dermatologist is best trained to complete a full and thorough skin examination and is best able to recognize a melanoma at its earliest stages of radial growth. In large part because of advances in dermatology, the dysplastic nevus syndrome has been identified as an important marker and precursor lesion for melanoma; the dermatologist has the best knowledge base for the recognition and management of both sporadic and familial dysplastic nevi. Dermatologists also have the unique opportunity (by virtue of their patient population concerned with skin problems) to prevent melanoma through patient education concerning sun protection, self examinations, and the ABCDs of melanoma recognition. The dermatologist is well trained to obtain an appropriate, full-thickness skin biopsy specimen and is also knowledgeable to interpret the pathologist's report, understanding the significance of the various histologic prognostic indices. Because of the changing trends in excisional margin size and fewer recommendations for ELND, the dermatologist is becoming more active in the surgical management of melanoma patients. In the MDMC, the dermatologist was clearly recognized as a capable surgeon to perform the wide local excisions for stage I patients. Almost one half of the patients seen (49%) were surgically treated in the department of dermatology. Of group I patients, 78% were treated by dermatologists. The dermatologist as surgeon should be capable of performing a wide local excision to the level of deep subcutaneous tissue or muscle fascia with an appropriate primary layered closure, local flap, or graft. Our experience confirms that the majority of patients present with local disease and a thin Breslow depth and thus can be skillfully treated in an outpatient setting under local anesthesia by a dermatologic surgeon. In follow-up, the dermatologist should provide continuity of care and should be knowledgeable in appropriate interval examinations and tests. The dermatologist is thoroughly skilled at the cutaneous examination and has the knowledge base to perform a careful and competent lymph node examination. As primary medical oncologist to these patients, the dermatologist needs to recognize stage II and stage III disease and be able to comprehensively discuss with the patient the options for treatment and how they affect their prognosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1934642 TI - Radiation therapy for cancers of the skin. AB - Although radiation therapy has been used in the treatment of skin tumors for many years, there has recently been considerable progress in the field. Improvements in available equipment, as well as a greater understanding of the radiobiologic behavior of tumors, have changed the nature of practice and its outcome. These changes and their impact are described in this article. Now more than ever, the practicing dermatologist needs a working knowledge of radiotherapy to manage patients' tumors in an optimal fashion. PMID- 1934643 TI - Distinguishing benign and malignant melanocytic lesions with the AgNOR method. AB - A silver staining technique has recently been devised to aid in the differentiation between benign and malignant melanocytic lesions. This study showed a statistically significant difference between the staining of silver nucleolar organizer regions (AgNORs) in melanocytic nevi and that of AgNORs in malignant melanomas. PMID- 1934645 TI - Longitudinal pigmented nail bands. AB - In this article, we have discussed the possible causes of a longitudinal pigmented nail band. A thorough history, physical examination, and, when indicated, biopsy of the origin of the band should reassure the patient with a benign lesion and direct further treatment of a patient with a malignant or potentially malignant lesion. PMID- 1934644 TI - Computer applications in the diagnosis and prognosis of malignant melanoma. AB - Recent advances in computer technology have begun to make computers a more effective tool in the diagnosis and evaluation of malignant melanoma. Preliminary computer-aided diagnosis programs have been developed. Histologic evaluation applications in both diagnosis and prognosis are also evolving. Further advances in computers may make them an integral part of the diagnosis and prognosis of melanoma in the future. PMID- 1934646 TI - Clinical features of dysplastic nevi. AB - The clinical features of 100 dysplastic nevi were tabulated. Although certain characteristics were present in most or all of these melanocytic nevi, there was a marked heterogeneity of other clinical features. The preponderant type of large (greater than or equal to 8 mm) melanocytic nevus in patients with classic dysplastic nevi is a papule or plaque with the following characteristics: multicoloration (various shades of tans, browns, reds, or black); slightly raised height for its broad diameter; mamillated surface; and lack of hypertrichosis. An atlas illustrates some of the clinical varieties of melanocytic nevi in this syndrome. PMID- 1934647 TI - Ocular findings in patients with dysplastic nevus syndrome. An update. AB - Two hundred fifty-seven patients with biopsy-proven dysplastic nevus syndrome (DNS) were evaluated ophthalmologically and compared with 264 non-DNS patients, who acted as a control population. A statistically significant increase in the percentage of the DNS patients versus controls harboring conjunctival nevi (8.56% vs. 1.14%), iris nevi (24.90% vs. 9.47%), and choroidal nevi (14.40% vs. 5.30%) was encountered. The number of iris nevi found per patient was also greater statistically for the DNS group. Also encountered in the DNS group was presence of multiple nevus types in the same patient (iris and choroidal, iris and conjunctival, conjunctival and choroidal); 3 patients had all three nevus types present, and 4 patients had two choroidal nevi per eye. No patient in the control group had more than one nevus type present per eye. PMID- 1934648 TI - Poorly differentiated skin tumors. Beyond hematoxylin-and-eosin staining. AB - Although many tumors may be diagnosed by light microscopy alone, a few require further investigation. Selective use of antibodies by immunohistochemical techniques solves most diagnostic problems. The explosive discovery of many new antibodies often raises more questions than it answers, and electron microscopy still plays a significant role when used judiciously. It is important to recognize that every new antibody must be adequately assessed in the clinical situation and that its specificity, or lack thereof, is appreciated by both clinician and pathologist. With every new antibody, we increase our knowledge of basic disease processes. In the future, antibodies will be part of the pathologist's armamentarium for predicting disease outcomes. Not only will the cell of origin be identified but proliferation rates and production of various factors that influence metastatic potential will be delineated. PMID- 1934649 TI - Incidence of nonmelanoma skin cancer. AB - Nonmelanoma skin cancers are the most common malignant neoplasms of fair-skinned people, in many sunny countries exceeding the total of all other neoplasms. The evidence that the primary causal agent is chronic repeated exposure to solar ultraviolet radiation is overwhelming. The incidence of basal cell carcinoma is always greater than that of squamous cell carcinoma, varying by latitude from 10:1 to 2.5:1. The incidence of nonmelanoma skin cancer has been increasing by 2% to 3% per year, at least in the United States. Most likely, this is caused by greater outdoor exposure for leisure and social reasons. PMID- 1934650 TI - Lasers in the treatment of skin cancer. AB - The development and use of various laser systems for the treatment of carcinomas of the skin constitute a relatively new therapeutic approach. Because the skin is a readily accessible organ, it is an excellent site at which to attempt different therapeutic modalities. What is truly astounding has been the development of specific lasers designed to treat certain dermatologic problems. Because the field of laser biotechnology is still rapidly emerging, it is very likely that new lasers and modifications of existing ones will improve our ability to treat skin cancer and precancerous conditions. PMID- 1934651 TI - Current concepts in Mohs micrographic surgery. AB - The evolution of fresh-tissue Mohs micrographic surgery is presented in this article. Special emphasis is given to accepted indications for Mohs micrographic surgery. Reconstructive techniques and certification in Mohs micrographic surgery are discussed. PMID- 1934652 TI - Sunscreen: one weapon against melanoma. AB - It is hoped that this review has given some information to direct the clinician in his approach to his patients. Certainly, we would desire that the incidence of malignant melanoma as well as other skin cancers would start to decrease. PMID- 1934653 TI - Can screening for melanoma and skin cancer save lives? AB - Although screening for melanoma and skin cancer is theoretically appealing, too few data exist to evaluate its effectiveness. The rising incidence and mortality rates of melanoma and the continued incurability of metastatic disease underscore the desperate need for effective screening. The extraordinary incidence of NMSC is a public health problem, but the value of screening for NMSC has not been established. The AAD screening program offers an opportunity to obtain critical data. Further research must make our screenings more effective and efficient. We need rigorous design and evaluation of all screening efforts. In the absence of a randomized controlled trial, other design measures, with careful tracking of incidence and mortality, are critical to assessing whether screening for melanoma and skin cancer can reduce morbidity and save lives. PMID- 1934654 TI - A review and update of the clinical uses of cyclosporine in dermatology. AB - Cyclosporine is a hitherto unique immunosuppressive agent that has provided a new approach to therapy in autoimmune diseases and has been increasingly used as a molecular tool for the investigation of immune regulation. It has produced excellent therapeutic responses in the treatment of psoriasis, acrodermatitis continua of Hallopeau, pyoderma gangrenosum, lichen planus, pityriasis lichenoides chronica, Behcets disease, and alopecia areata. Cyclosporine's mechanism of action, side effects, pharmacokinetics, and guidelines for patient monitoring, are discussed in this article. PMID- 1934655 TI - Increased plasma interleukin 6 and renin substrate levels during bacterial peritonitis in CAPD patients. PMID- 1934656 TI - Comment on "The clinical significance of the glomerular location of segmental lesions in focal glomerulosclerosis". PMID- 1934657 TI - Parahilar hyaline deposits and focal segmental glomerulosclerosis. PMID- 1934658 TI - Transplantation and nephrectomy in autosomal dominant polycystic disease. PMID- 1934659 TI - Growth-related changes in echocardiographic measurements. PMID- 1934660 TI - The impact of prolonged immunosuppression on the outcome of idiopathic focal segmental glomerulosclerosis with nephrotic syndrome in adults. A collaborative retrospective study. AB - In this retrospective study we report the outcome of 59 adults with idiopathic focal-segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS) treated with corticosteroids and/or immunosuppressive drugs. Twenty-seven patients were initially treated with corticosteroids alone for 9.3 +/- 8 months; nineteen patients received corticosteroids and immunosuppressive agents associated or every other month for 5.5 +/- 4 months; thirteen patients received either azathioprine or cyclophosphamide alone for 25 +/- 27 months. At the end of a mean follow-up of 75 +/- 51 months, 35 patients (60%) were in complete (CR) or partial (PR) remission, 6 (10%) were stable and 18 (30%) had either chronic renal failure (CRF) or end-stage renal failure (ESRF). Out of 36 patients (61%) initially responsive to therapy, 30 (83%) obtained CR, 4 (11%) PR, one (2.7%) developed CRF and one (2.7%) ESRF. Only 10 of the responders (28%) attained remission within 8 weeks of treatment. Out of the 23 (39%) patients originally resistant to therapy, only one (4%) had CR, 6 (26%) remained unchanged, 6 (26%) developed CRF and 10 (43%) ESRF. The presence at initial renal biopsy of interstitial fibrosis was the only feature which could predict a poor renal outcome. These data show that prolonged treatment of FSGS can obtain sustained remission of the disease and improved renal survival in a consistent proportion of adult patients which would be considered refractory to a two-month course with corticosteroids. PMID- 1934661 TI - Effects of triple therapy in IgA nephritis: a follow-up study 5 years later. AB - This study is a 5-year post trial assessment of patients with IgA nephritis who entered a 3-year prospective controlled trial of cyclophosphamide, dipyridamole (D) and low-dose warfarin (W). Patients entered the trial from 1979 to 1981 and the trial ended in 1984 with those in the treatment group having more stable renal function and less proteinuria compared to the control group. Present reassessment of the patients in 1989 showed no difference in the renal function between those in the treatment group (n = 27) and the control group (n = 21). 6 patients in the treatment group and 7 in the control group were in ESRF. At the conclusion of the trial in 1984, among the 27 patients in the original treatment group, 13 patients elected to continue with D + W while the other 14 patients chose to cease therapy and therefore served as the new control group. 5 years later, renal function in the new treatment group (n = 13) was significantly stable compared to the new control group (n = 14), (serum creatinine 1.4 +/- 0.7 versus 4.4 +/- 3.2 mg/dl, p less than 0.01). Furthermore, all the 6 patients with ESRF in the original treatment group of 27 patients were from the new control group (n = 14) where treatment with D + W had been ceased. None of the patients still on D + W are in ESRF. PMID- 1934662 TI - Intraglomerular lipid deposition in routine biopsies. AB - Studies have suggested that lipids participate in the pathogenesis of chronic progressive glomerulosclerosis. To examine the frequency of intraglomerular lipid deposition in routine biopsies, renal biopsy material from 631 consecutive patients with glomerular lesions was studied by light, electron, and immunofluorescence microscopy. Fifty-three patients (8.4%) revealed ultrastructurally detectable lipid deposits in nonsclerotic glomeruli. Seven had minimal lesion, 13 focal-segmental glomerulonephritis, two membranous nephropathy, nine membranoproliferative glomerulosclerosis, 11 IgA nephropathy, and 11 other diseases. Ultrastructurally, the lesion affected small segments of glomeruli, with clusters of lipids which exhibited a heterogenous pattern. A subendothelial accumulation of lipids was observed in 60%, storage of lipids on mesangial matrix in 68%, and intramembranous deposition in 21%. Intracellular accumulation of fat was noted in 23%. Indirect immunofluorescence testing for apolipoprotein B (apo B) and oil red O (ORO) staining were performed in 94 cases. Positive results for apo B and ORO staining in nonsclerotic glomeruli were obtained in 24 patients (26%) and 16 cases (17%), respectively. The distribution of lipids seen in these patients was either in diffuse or focal segmental patterns. The clinical data of 40 patients with glomerular lipid deposition were compared with 80 controls from the residual group of patients matched for age, sex, and disease. Serum creatinine and cholesterol levels, and daily excretion of urinary protein were not significantly different between the two groups. These results suggest that an abnormal accumulation of lipids, mainly of apo B containing lipoprotein, in nonsclerotic glomeruli from routine biopsies is not as rare as previously thought. In addition, factors other than hypercholesterolemia seem to be operative for the glomerular lipid deposition observed in our patients. PMID- 1934663 TI - The kidney disease of Crow-Fukase (POEMS) syndrome: a clinico-pathological study of four cases. AB - We studied four cases of Crow-Fukase syndrome with renal dysfunction. Kidney specimens obtained by needle biopsy showed glomerular lesions resembling those seen in conditions characterized by microangiopathy. Common glomerular findings by light microscopy were mesangial expansion and narrowing of the capillary lumina. An enlarged subendothelial space and mesangial area with deposition of amorphous material as well as swelling and vacuolization of endothelial cells were observed by electron microscopy. In an active phase, severe mesangial edema and segmental mesangiolysis, and in a late stage, mesangial cell interposition and sclerosis were seen. Tests by immunofluorescence microscopy for the presence of immunoglobulins A, M, G, lambda and kappa light chains, C3, and C4 were negative. Decay accelerating factor was found in glomeruli and in the vascular pole. Other findings included lymph node angiosclerosis, peripheral nerve microangiopathy and hemangioma formation with endothelial cell proliferation. These observations suggest that chronic endothelial injury constitutes the basic pathology of Crow-Fukase syndrome. Hemodialysis was required to manage anasarca in three of the patients although serum creatinine levels were below 5.0 mg/dl. Urinalysis revealed mild abnormalities and did not reflect the severity of the glomerular lesion. Corticosteroids given to three of the patients were effective in controlling fever and the lymphadenopathy; in two cases the corticosteroids induced a recovery of renal function. Thus Crow-Fukase syndrome may be due to chronic endothelial injury; the clinical symptoms and renal involvement respond to corticosteroid therapy. PMID- 1934664 TI - Pulmonary and renal toxicity of intravenous immunoglobulin. AB - Three patients treated with intravenous immunoglobulin developed respiratory difficulty and decreased renal function. Previously reported adverse reactions to this class of drugs have included pulmonary toxicity but not, to the best of our knowledge, renal toxicity. Renal dysfunction was mild in one patient but severe in two patients, one of whom required temporary hemodialysis. In all three patients, renal function returned to the pretreatment level after stopping the drug. Urinalysis and urine sodium concentration at the onset of renal failure were consistent with pre renal azotemia although renal biopsy performed later in one patient showed acute tubular necrosis. The exact mechanism of toxicity is unknown, but the fact that all three cases occurred with a particular immunoglobulin preparation would suggest that a contaminant, possibly aggregated IgG might be responsible. PMID- 1934665 TI - Renal vasoconstriction after low and high osmolar contrast agents in ischemic and non ischemic canine kidney. AB - We have assessed the effect of contrast media on renal blood flow before and after inducing renal ischemia. Diatrizoate, iopamidol and ioxaglate were injected within 15 seconds at 20 min intervals, at the dose of 1 ml/kg during a control period and 15 min after applying an aortic clamp to reduce the renal perfusion pressure to 70 mmHg. During the control period iopamidol, ioxaglate (17 +/- 13%) and diatrizoate (16 +/- 2%) induced a comparable decrease in renal blood flow (RBF). During the ischemic period the effects of diatrizoate on renal hemodynamic were dramatically enhanced. Ioxaglate andiopamidol induced a 20 +/- 12 and a 32 +/- 9% decrease in RBF at 1 minute, respectively. Iopamidol induced an increase in renal vascular resistance (RVR) from 0.8 +/- 0.08 to 1.46 +/- 0.26 mmHg min/ml (p less than 0.05). Ioxaglate induced an increase in RVR from 0.8 +/- 0.09 to 1.36 +/- 0.38 (p less than 0.05). Diatrizoate induced a 77 +/- 10% decrease in RBF and a maximum increase in RVR at 1 minute from 0.9 +/- 0.09 to 26 +/- 12 mmHg min/ml. There was still a 36 +/- 14% and a 23 +/- 13% decrease in RBF 10 and 20 min after diatrizoate administration. These changes were significantly higher than those observed with all contrast media during the control period and low osmolar contrast media during the ischemic period. We have thus shown that ischemia potentiates the renal vascular effect of contrast media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934666 TI - Intragastric long-term pH-metry in hemodialysis patients. A study with famotidine. AB - The onset and duration of famotidine action were studied in 14 hemodialysis (HD) patients and 16 healthy controls (control group: CG) who were examined by ambulatory intragastric 24-hour pH-metry. 20 mg famotidine was administered i.v. 90 min after HD in the afternoon (AN; 2 p.m.; n = 8) or evening (E; 8 p.m.; n = 6), followed by a standard meal. Mean onset of action in the AN and E groups of the HD patients was 90.3 +/- 28.2 min and 98.8 +/- 29.8 min, and in CG patients 36.3 +/- 11.9 min and 53.6 +/- 22.3 min, respectively (p less than 0.05). Duration of action in the AN and E groups of the HD patients was 22.7 +/- 2.1 h and 21.6 +/- 2.6 h, and in CG patients 6.0 +/- 1.1 h and 11.4 +/- 1.6 h, respectively (p less than 0.05). Our study showed a retarded and prolonged action of famotidine in HD patients. The time of administration of famotidine had no effect on its action in HD patients. This is in contrast to normal subjects in whom evening administration delays the onset and prolongs the duration of famotidine action in comparison to afternoon administration. PMID- 1934668 TI - Immunohistological localization of apolipoproteins in the glomeruli in renal disease: specifically apoB and apoE. AB - Recently it has become clear that abnormalities of the lipid metabolism may play a large role in the progression of renal diseases. To investigate the relationship between lipids and kidney tissues, the authors employed an immunofluorescent technique to determine the presence of apolipoprotein (apo) B and E in kidney tissue, particularly the glomeruli, and analyzed the relationship between their deposition and the clinical and histological findings of a total of 49 patients with persistent proteinuria and/or hematuria (age range: 10 to 62 years). The patients were divided into 4 groups, as follows: both apoB and apoE negative cases (Group 1; 17 cases), apoB alone positive (Group 2; 7 cases), apoE alone positive (Group 3; 10 cases) and both apoB and apoE positive cases (Group 4; 15 cases). Group 2 had more severe proteinuria and a higher level of total cholesterol than Group 1. Group 3 exhibited a higher incidence of glomerular adhesion and interstitial changes than Group 1. Group 4, on the other hand, exhibited more severe mesangial hypercellularity and a higher incidence of glomerular sclerosis and interstitial scarrings than Group 1, a higher incidence of glomerular sclerosis than Group 2, more severe proteinuria, higher serum levels of total cholesterol, and lower serum levels of total protein than Groups 1 and 3 and higher level of uric acid than Group 1. These results suggest that the deposition of apoB and apoE accelerates the progression of mesangial lesions, resulting in greater proteinuria and glomerular sclerosis. PMID- 1934667 TI - Immune material processing by phagocyte cell system in cryoglobulinemia. AB - An impaired function of splenic macrophages, measured as the clearance rate of erythrocytes coated with IgG (E-IgG), was observed in 7 out of 8 cryoglobulinemic patients with severe urinary abnormalities and systemic symptoms, and in 0 out of 6 patients without urinary symptoms and only mild systemic signs of disease. The E-IgG clearance rate was not related to HLA or Rh phenotype, patients' age or disease duration. Moreover, longitudinal studies showed this parameter to be strictly related to disease activity. To investigate the nature of the defect, five series of analyses were planned using peripheral blood phagocytes (PBP) from 8 patients: a) detection of cell-bound immune material by using the antibody CE59 directed to the Fc fragment of IgG modified by the antibody-antigen reaction; b) cytofluorometric and/or radiometric analyses of the cell surface expression of HLA II, CR1 and FcR structures by means of specific monoclonal antibodies (MoAbs); c) electron microscopy (EM) examination of diverse combinations of cryoglobulins incubated with PBP from patients and normals; d) analysis of cryoglobulin-induced inhibition of E-IgG phagocytosis; e) measurement of the generation of chemiluminescence (CL) in response to Zymosan, Phorbol Myristate Acetate and n-Formyl-Methyonine-Leucine-Phenilalanine (n-FMLP). Patients' PBP were found to have a higher amount of cell-bound immune material as compared to normals (p less than 0.01). CR1 and FcR expression was not different from controls, whereas a slight increase in percentage of monocytes bearing HLA II structures was found in patients (p less than 0.05). Upon EM examination no obvious differences were found in the internalization capacity of cryoglobulins between patients and controls. The CL production was lower than normal (p less than 0.02), whatever stimulus used, with a maximal impairment for n-FLMP (p less than 0.005), the most specific test probe for cytoskeleton integrity. Finally, a remarkable cryoglobulin-induced inhibition of E-IgG phagocytosis was shown. A combination of saturation mechanisms and intracellular abnormalities could underlie the apparent discrepancy between E-IgG clearance defect and preserved potential of cryoglobulin internalization in cryoglobulinemia. PMID- 1934669 TI - FSGS-like lesions in pre-eclampsia. AB - Renal-biopsy specimens taken from pre-eclamptic patients are associated sometimes with focal-segmental glomerular sclerotic lesions (FSGS-like lesions) that closely resemble those of primary focal-segmental glomerulosclerosis. We studied a series of 60 sections from each of 19 cases of "pure" pre-eclampsia by light microscopy. Group I comprised 13 patients with FSGS-like lesions in their glomeruli, group II comprised 6 patients without such lesions. FSGS-like lesions were observed in 20.7 +/- 4.6% of glomeruli in group I. Epithelial droplets were observed in 12 of 13 cases in group I, but only one of 6 cases in group II. The incidence of granulated glomerular epithelial cells was significantly higher in group I (p less than 0.0005). The double contour of the basement membrane was more severe in group I than in group II (p less than 0.03). The percentage of glomeruli with FSGS and the number of weeks during which proteinuria of greater than or equal to g/day continued after delivery were positively correlated (r = 0.76, p less than 0.0002). We also found a significant positive correlation between the percentage of glomeruli with FSGS and the amount of proteinuria at delivery and biopsy (r = 0.66, p less than 0.003; r = 0.51, p less than 0.03). However, proteinuria disappeared in all patients. Three of them had successful second pregnancies. We consider that FSGS-like lesions can occur during pregnancy in "pure" pre-eclamptic patients but the lesions may not be progressive. We also suggest that proteinuria and epithelial cell change may be closely related with such lesions. PMID- 1934670 TI - Clinical significance of serum and urinary neopterins in patients with chronic renal disease. AB - To determine the clinical significance of serum and urinary neopterins in patients with chronic renal disease, we measured these values using IMMUtest Neopterin RIA kits. Serum neopterin levels in patients with chronic glomerulonephritis (CGN) (10.2 +/- 8.1 nmol/l) and in those with chronic renal failure (CRF) (109 +/- 90) were significantly increased compared with the control subjects (C) (4.2 +/- 2.4) (p less than 0.001). The levels of serum neopterins in patients on chronic hemodialysis (HD) (212 +/- 106) were increased almost twofold compared with CRF (p less than 0.001). In CGN and CRF, a strong positive correlation was demonstrated between serum neopterin levels and serum creatinine concentrations (r = 0.95, p less than 0.001). In HD patients, neopterin levels and serum were not correlated with the length of time on dialysis. The urinary neopterin excretion ratios (urinary neopterin/urinary creatinine level) in CRF (227 +/- 114 mumols/molCr) were significantly increased compared with C (116 +/- 43) (p less than 0.01). A significantly negative correlation was observed between the urinary neopterin levels and the creatinine clearance in CGN and CRF (p less than 0.01). These data suggest that, in patients with chronic renal disease, the neopterin levels in serum are closely linked with glomerular filtration rate and yet the urinary neopterin/creatinine ratios may reflect the predominance of increased tubular secretion of neopterin over the renal injury per se. PMID- 1934671 TI - Myocardial revascularization in patients on renal replacement therapy. AB - Coronary disease is the main cause of mortality and morbidity among long-term survivors on renal replacement therapy (RRT). Despite the additional risk factors, myocardial revascularization has been recently attempted with various success in some patients on RRT. We report on 26 patients (13 dialyzed and 13 transplanted, mean age: 50 years [range 38-66]) who have undergone either surgical aorto-coronary bypass (CABG) (n = 16) with mammary artery grafts, or percutaneous coronary angioplasty (PTCA) (n = 9), or both procedures (n = 2). Indication was angina pectoris in all but three patients with painless ischemia. Eight patients had unstable angina (NYHA class IV). A previous myocardial infarction was documented in 11 cases. Coronary angiography disclosed mainly multiple vessel disease (81%). Post CABG complications consisted of severe intrathoracic bleeding (n = 3) resulting in death in 2 cases. PTCA entailed no major complication. After the critical postoperative period, the long-term survival was the same as that of non-uremic patients and the clinical improvement, according to the NYHA classification, was highly satisfactory at 6 months and persists up to 2 years. We conclude that coronary angiography and myocardial revascularization should be considered in patients on long-term RRT developing coronary disease. PMID- 1934672 TI - Pregnancy in women with focal hyalinosis and sclerosis. PMID- 1934673 TI - Comment on "Red blood cell destruction in single-needle dialysis" by Dhaene et al. PMID- 1934674 TI - Comment on "Irreversible ocular toxicity from single challenge dose of desferrioxamine" by C. Bene et al. PMID- 1934675 TI - Comment on "Long-term prognosis of chronic idiopathic membranous glomerulonephritis" by M. Wehrmann et al. PMID- 1934676 TI - Acute renal failure induced by oral acyclovir. PMID- 1934677 TI - Turbid dialysate effluent and bacterial peritonitis. PMID- 1934678 TI - Erythropoietin and improvement in the erythropoiesis of chronic hemodialysis patients treated with desferrioxamine. PMID- 1934679 TI - Aggravation of palmar erythema by an arteriovenous fistula. PMID- 1934680 TI - The hepatic complications of the antiphospholipid antibodies. PMID- 1934681 TI - Lupus nephritis: the significance of serological tests at the time of biopsy. AB - We reviewed the initial serological data of 50 patients with biopsy-proven lupus nephritis. As compared with a group of lupus patients without nephritis, patients with nephritis had lower serum complement C3 (p less than 0.05) and C4 (p less than 0.005) levels and higher serum DNA binding activity (p less than 0.001). The frequency of rheumatoid factor, antiphospholipid, anti-ENA, and fluorescent antinuclear antibodies was similar in both groups. We correlated the serological data of the patients with nephritis with the clinical severity of their disease. Using a functional staging system based on the serum albumin and creatinine levels at the time of biopsy, we found that patients with functionally milder disease (proteinuria without nephrotic syndrome or renal failure) had higher C3 (p less than 0.05) and lower DNA binding (p less than 0.005) than patients in the more severe functional classes (nephrotic syndrome with or without renal failure). In contrast, C4 levels were always very low, irrespective of functional severity. We also correlated the serological data with the pathological findings. Patients suffering from diffuse proliferative nephritis had higher DNA binding values than patients with focal proliferative (p less than 0.01) or membranous (p less than 0.001) nephritis. By contrast, complement levels were not correlated with the severity of biopsy changes. Taken together, the data presented here suggest that C3 and DNA binding, but not C4, correlate with the clinical severity of lupus nephritis at presentation whereas DNA binding, but not complement levels, correlates with the severity of pathological changes. PMID- 1934682 TI - High incidence of polymyalgia rheumatica and giant cell arteritis in a Swedish community. AB - The minimum incidence of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) was studied during one year in a stable Caucasian population in southern Sweden. The data obtained show an incidence rate higher than that previously found in Sweden and almost as high as the rate recently found in Denmark. In addition, the finding of a low incidence of ocular complications during 3 years of follow-up suggests the positive influence of training primary health care physicians to identify and treat these patients early. Furthermore, the previously described transition from pure PMR into GCA was not seen which might imply a further effect of early treatment. PMID- 1934683 TI - Sneddon's syndrome: cardiac pathology and antiphospholipid antibodies. AB - Forty-one patients (31 women, 10 men) aged 15-56 (mean age, 38) with Sneddon's syndrome characterised by cerebrovascular disease and widespread livedo reticularis in the absence of typical lupus features were studied. 16 patients (39%) had clinical and/or electrocardiographic signs of ischemic heart disease, with 2 of them having survived myocardial infarction. Cardiac murmurs (usually mitral systolic) were heard in 15 patients (37%). Echocardiography revealed mitral valve thickening in 13 of 32 tested patients (41%). Anticardiolipin antibodies were found in 22 patients (54%) and lupus anticoagulant in 25 of 38 tested patients (66%). In 6 patients (15%) neither anticardiolipin antibodies nor lupus anticoagulant were observed. Anticardiolipin antibodies were more often present in patients with ischemic heart disease (12 of 16), than in those without (10 of 25) (p less than 0.05). Mitral valve thickening was revealed more often in patients with antiphospholipid antibodies (12 of 26 patients) than in those without (1 of 6); however, a statistically significant difference was not observed. PMID- 1934684 TI - Correlation between rheumatoid factor and IL-6 activity in synovial fluids from patients with rheumatoid arthritis. AB - Synovial fluids (SF) and sera (S) from patients with rheumatoid arthritis (RA) were examined for IgM, IgM-rheumatoid factor (IgM-RF), albumin and interleukin-6 (IL-6) activity. The quotient of SF/S IgM-RF was elevated compared with that of SF/S albumin in 7 patients with seropositive RA, although the quotient of SF/S IgM was lower than that of SF/S albumin. SF IL-6 activity was much higher than serum IL-6 activity in all the 7 RA patients. In synovial fluids from 22 seropositive RA patients, SF IL-6 activity was significantly correlated with the SF IgM-RF, IgG-RF and IgA- less than RF, but not with SF IgM, IgG or IgA. Moreover, SF IgM-RF as well as SF IL-6 activity was significantly correlated with the Westergren erythrocyte sedimentation rate (ESR) or the Lansbury articular index. These results indicate that IL-6 and RF might be produced within the rheumatoid joints as a result of abnormal immune system activation, which is associated with the disease activity of RA. Three of the 4 seronegative RA patients, however, showed high SF IL-6 without detectable levels of SF IgM-RF, indicating that IL-6 alone is not sufficient for IgM-RF production. PMID- 1934685 TI - The in vitro effect of six NSAIDs on the glycosaminoglycan metabolism of rabbit chondrocytes. AB - The effects of NSAIDs on glycosaminoglycan (GAG) metabolism in vitro were studied in isolated chondrocytes from the weight-bearing cartilage of the hindleg knees of five mature rabbits separately. After confluence, secondary cultures were incubated for three days with six different NSAIDs at various concentrations: diclofenac sodium and indomethacin (0.4-50 micrograms/ml), piroxicam, naproxen and ibuprofen (4-100 micrograms/ml) and salicylic acid (8-1000 micrograms/ml). All NSAIDs significantly inhibited total 35S uptake in GAGs both in matrix and in medium in high concentrations. At low concentrations none of the NSAIDs significantly influenced the chondrocyte metabolism of GAG. The NSAID influence on keratan sulphate metabolism was variable. PMID- 1934686 TI - Intra-articular treatment of knee osteoarthritis. A comparative study between hyaluronic acid and 6-methyl prednisolone acetate. AB - The efficacy and tolerability of 20 mg of hyaluronic acid were compared in an open, randomized trial with that of 40 mg of 6-methylprednisolone acetate, administering them both by an intra-articular route once a week for 3 weeks to patients suffering from inflammatory knee osteoarthritis. The results of the study showed that for up to one week after the end of treatment hyaluronic acid's analgesic activity was comparable to that of the steroid, while at the end of the follow-up (45 days after the end of treatment) all the pain monitoring parameters presented significant differences in favour of the HA-treated group. Both treatments were well tolerated, since no local or systemic adverse reactions were observed. PMID- 1934687 TI - Efficacy of cyclosporin A in systemic sclerosis. AB - In this open pilot study, the potential therapeutic efficacy of Cyclosporin A (CsA) in systemic sclerosis (scleroderma) was investigated. Eight patients with severe scleroderma (skin manifestation and at least three organ manifestations such as pulmonary, intestinal, cardiac, renal, and severe hypertension) were included in the study. CsA administration was started at a dose of 5 mg per kg body weight per day and then, to obtain whole blood levels of 300-500 ng/ml, adjusted to a mean dosage of 4.3 mg/kg/day. Therapeutic effects were evaluated by monitoring the measures of cutaneous, pulmonary, cardiac, gastrointestinal, and renal involvement as well as laboratory parameters. After 6 to 12 months of CsA administration, cutaneous abnormalities improved in seven, arterial oxygen tension slightly increased in four, pulmonary hypertension decreased in five, and smooth muscle esophageal contraction amplitudes improved in three patients. However, the disease progressed in one patient. No serious side effects were observed, and occurring renal side effects were mild. Taken together, these observations indicate that CsA administration may be effective mainly in the skin involvement, but also in some organ manifestations of scleroderma. The results of this pilot investigation therefore indicate that a controlled study of the efficacy of CsA in scleroderma is needed and ought to be performed. PMID- 1934688 TI - Human monocyte elastolytic activity, the propeptides of types I and III procollagen, proteoglycans, and interleukin-6 in synovial fluid from patients with arthritis. AB - Elastolytic activity by live human monocytes (M phi) is mainly caused by cell surface related leucocyte elastase, capable of degrading matrix components. In order to examine the possible correlation between enzyme activity and tissue turnover in the joint, we examined 24 synovial fluids for M phi elastolytic activity, using the levels of synovial fluid interleukin-6 and serum C reactive protein as additional markers of cell activation. Proteoglycan levels were measured as an indication of cartilage degradation and the types I and III procollagen propeptides as markers of synovial membrane turnover. We found that elastolysis by live M phi and the levels of interleukin-6 and C reactive protein correlated significantly with proteoglycan concentrations but not with the procollagen propeptides. These findings suggest that human M phi elastolytic activation is a biologically relevant factor in cartilage degradation, but is unrelated to the collagen metabolism of the synovial membrane. PMID- 1934689 TI - von Willebrand factor in synovial fluid. AB - Von Willebrand factor (vWf), an endothelial product that arises in plasma in conditions associated with vascular damage and acute phase reaction, was evaluated in paired samples of plasma and synovial fluid obtained from 54 patients with inflammatory joint effusion, 19 patients with osteoarthritis, and from the plasma of 19 controls. Synovial fluid levels of vWf were detected in 36 of the patients. The mean value of vWf in the inflammatory joint effusion group was 18.27 +/- 3.03%, significantly higher than the mean value of 7.7 +/- 4.4% found in the osteoarthritis group (p less than 0.01). The significant difference between these groups was maintained when vWf was expressed as a ratio of albumin. vWf was correlated with synovial fluid levels of alpha-1-antitrypsin (r = 0.83, p less than 0.01) and with the white cell count (r = 0.74, p less than 0.01), but not with the levels of immunoglobulins or C3. vWf in the synovial fluid may reflect the local degree of inflammation. PMID- 1934690 TI - Immunochemical characteristics of a particular cryoglobulin. A new cryoglobulin subgroup? AB - In a patient (BAR) affected by chronic active hepatitis we isolated a cryoglobulin constituted of polyclonal IgM (k and lambda) and a monoclonal IgG3 lambda. The IgM represented the antibody of the cryoglobulin complex. This type of cryoglobulin, where the monoclonal component is the antigen and not the antibody, cannot be correctly classified using the nomenclature of Brouet et al. (1) currently in use. In this patient a two-year follow-up excluded any clinical signs of cryoglobulin toxicity. The immunochemical and clinical characterization of other cryoglobulins similar to BAR could establish a new homogeneous group. PMID- 1934691 TI - Diet and fatty acids: can fish substitute for fish oil? AB - As fish oil has been shown to be beneficial in rheumatoid arthritis and in psoriasis, we examined whether a diet rich in fish has a similar effect on membrane and plasma lipids as a dietary fish oil supplement. Volunteers recruited by 2 rheumatology units in Switzerland formed three parallel groups eating respective diets during 2 months: a normal diet without fish; a normal diet including 700 g fish per week; a normal diet without fish but with additional fish oil (7.5 g daily). As outcome measures we determined the lipid composition of platelet-rich plasma, the serum cholesterol and triglycerides before the study and after 1 and 2 months of the designated diet. The relative amounts of both eicosapentaenoic acid and docosahexaenoic acid increased significantly in the fish oil group and in the group with the fish diet; no change was seen in the control group. The effect on triglycerides, which were low at the beginning of the study, was minor and no change in cholesterol was seen. In conclusion, 4 to 6 meals with fish per week without any other dietary changes can induce similar changes in lipids as a supplement of fish oil. PMID- 1934693 TI - Isolated septic meningococcal arthritis. AB - Among the different types of arthritis associated with meningococcal disease, isolated primary meningococcal arthritis is unusual. A case of isolated group C meningococcal septic arthritis in an HIV negative homosexual male is described and its possible implication discussed. PMID- 1934692 TI - SLE and acute Addisonian crisis due to bilateral adrenal hemorrhage: association with the antiphospholipid syndrome. AB - This report describes a 68-year-old woman with SLE and positive antiphospholipid antibodies who developed an acute Addisonian crisis due to bilateral adrenal hemorrhage. We suggest that adrenal bleeding can be part of the thrombo-embolic complications seen in the secondary antiphospholipid syndrome. PMID- 1934694 TI - Glucocorticosteroid action on the immune system: molecular and cellular aspects. AB - The history of glucocorticosteroid therapy and modern rheumatology are inseparable. Glucocorticosteroids exert profound effects on the inflammatory and immune responses. They affect the growth, differentiation and function of monocytes and lymphocytes, the distribution of cellular subsets, and the production of cytokines. Glucocorticosteroid-induced lipocortins inhibit eicosanoid production and release by suppressing phospholipase A2. The principal mechanism whereby they exert their powerful effects is through modulation of the transcription of specific sets of genes. Recently, post-transcriptional mechanisms have also been recognized to be affected by glucocorticosteroids. In this review we discuss the molecular and cellular aspects of glucocorticosteroid action on the immune system. PMID- 1934696 TI - Juvenile chronic arthritis in a Turkish population. AB - The clinical characteristics of 147 Turkish patients with juvenile chronic arthritis seen between 1980 and 1988 were analyzed retrospectively. There was a male predominance (1.3:1), and a relatively low occurrence of early onset pauciarticular disease (16%), chronic anterior uveitis (7%) and positive antinuclear antigens (6%), but a high incidence of secondary amyloidosis (10%) was seen. PMID- 1934697 TI - Sjogren's syndrome in human immunodeficiency virus (HIV) infection: association with HLA-DR3 and CD8 lymphocytosis in an Italian patient. PMID- 1934695 TI - Childhood systemic lupus erythematosus: a review of 30 cases. AB - We review 30 cases of pediatric systemic lupus erythematosus followed over an 8 year period at our institution. The female to male ratio was 3.3:1; the age at diagnosis ranged between 3.5 and 16 years. On first admission, renal involvement was detected in the majority of the patients, as assessed by laboratory findings and/or clinical manifestations. Other frequently observed symptoms were fever, skin rashes, arthralgias and/or arthritis and serositis. All of the patients were treated with corticosteroids and most of them also received immunosuppressive drugs in order to control disease activity. Two patients were lost to the follow up, five died and only one of the 23 evaluable patients is off therapy after a median follow-up of 5 years. This study confirms that pediatric systemic lupus erythematosus is a very aggressive disease. PMID- 1934698 TI - Hyperthyroidism and systemic lupus erythematosus: chance or genetic predisposition? PMID- 1934699 TI - Familial segregation of antiphospholipid serology from clinical features. PMID- 1934700 TI - Etiology and prevention of congenital anomalies among infants of overt diabetic women. PMID- 1934701 TI - Insulin management of type I and type II diabetes in pregnancy. PMID- 1934702 TI - Diabetic nephropathy and pregnancy. PMID- 1934703 TI - Diabetic retinopathy. AB - This review suggests the following risk factors which accelerate the natural progression of retinopathy during pregnancy: 1. Pregnancy per se is an independent risk factor which accelerates retinopathy. 2. Hypertension potentiates this acceleration. 3. Hyperglycemia also potentiates this acceleration. 4. The duration of diabetes and state of the retina at the beginning of the pregnancy influences the rate of acceleration. 5. Rapid normalization of blood glucose accelerates the progression of retinopathy. Prudent therapy would suggest that a pregnancy be planned to be able to normalize the blood glucose slowly (over 6-8 months) before conception. In addition, although there are no clinical trials, photocoagulation treatment should be according to the recommendations of the Diabetic Retinopathy Study despite the possibility that retinopathy may regress spontaneously postpartum. Unfortunately, clinicians often are faced with a fait accompli--the diabetic woman with retinopathy presents already pregnant. In this circumstance, we would recommend acute normalization of blood glucose with intensive surveillance of the retinal status and aggressive retinal treatment as necessary. PMID- 1934704 TI - The role of ultrasonography in the management of diabetic pregnancy. PMID- 1934705 TI - Fetal surveillance in the pregnancy complicated by diabetes mellitus. AB - During the last decade, outpatient protocols have been developed for antepartum fetal assessment in pregnancies complicated by diabetes mellitus. This approach has been associated with a markedly reduced cost of health care and emotional stress for patients and their families attributable to lengthy hospitalization. These programs have used primarily biophysical testing, with twice weekly NSTs followed by a CST or biophysical profile when necessary. Most recently, Doppler studies have been investigated as a method for identifying fetal compromise. Maternal assessment of fetal activity can be used as a screening test in most surveillance programs. Essential to the success of these protocols has been our ability to monitor maternal glycemia and to maintain glucose levels in the physiologic range through aggressive therapy with insulin and diet. Reassuring tests of fetal condition are present in most diabetic women and therefore permit fetal maturation to take place before delivery. PMID- 1934707 TI - Management of gestational diabetes. AB - The treatment of gestational diabetes is based on maintaining near-normal maternal glucose levels. To accomplish this goal, dietary counseling is used. circulating glucose is measured regularly, and exogenous insulin is sometimes necessary. Early delivery is not routine. Cesarean section is reserved for obstetric indications, but the presence of fetal macrosomia may be responsible for increasing the overall cesarean section rate in individuals with this disorder. The most important component of the treatment of gestational diabetes is probably the identification of the individual with this condition. PMID- 1934706 TI - Rationale and performance of tests for gestational diabetes. PMID- 1934708 TI - Contraception in diabetic women. PMID- 1934709 TI - Inheritance of type I diabetes mellitus. PMID- 1934710 TI - Bacterial vaginitis. AB - Bacterial vaginitis is responsible for approximately 10 million office visits per year. This condition may disrupt marriages and cause psychologic stress that may be reflected in the individual's work and social life. Bacterial vaginitis also has been thought to lead to postpartum endometritis, pelvic cellulitis, pelvic inflammatory disease, and chorioamnionitis. PMID- 1934711 TI - Current concepts in the treatment of invasive vulvar carcinoma. PMID- 1934712 TI - Gynecologic care of the human immunodeficiency virus-positive woman. PMID- 1934713 TI - Erosive lichen planus of the vulva. PMID- 1934714 TI - Vulvar dermatoses. AB - Benign and malignant vulvar disorders may look alike, making diagnosis difficult for even experienced vulvologists. Understanding basic principles of differential diagnosis and diagnostic testing is necessary for good medical or surgical management. Skin diseases do not respond quickly even when treatment is appropriate. Therefore it is especially important to establish the correct diagnosis as early as possible. This group of dermatoses demands careful distinction of sometimes subtle differences, but the physician and patient will be rewarded by a sure response to correct therapy. PMID- 1934715 TI - Superficially invasive carcinoma of the vulva. PMID- 1934717 TI - Carcinoma in situ of the vulva. PMID- 1934716 TI - Immunologic factors influencing susceptibility to recurrent candidal vaginitis. PMID- 1934718 TI - The frequency of occurrence of congenital dysplasia of the hip in Poland. AB - In Poland, the number of newborn infants suffering from congenital dysplasia of the hip (CDH) is high. Its percentage has not changed during the past 30 years. The aim of this paper was (1) to find the frequency of occurrence of CDH based on the highest possible number of cases and to obtain the most objective data from examination performed by orthopedic surgeons; (2) to gather information about methods of treatment used; (3) to establish time of treatment (depending on how advanced the dysplastic process was); and (4) to determine the number of complications. The data are based on 17,094,000 inhabitants, or 46.2% of the Polish population. During the years 1980 to 1984, about 350,000 deliveries were annually registered. On the basis of the data, the following were concluded: (1) The frequency of CDH among children in Poland comes to 6.8%. (2) Cases of dysplasia with dislocation are 1.06%. (3) Almost half the number of children (46.2%) are being treated in outpatient departments run by orthopedic surgeons. The remainder are being cared by pediatric and general surgeons, or pediatricians. (4) Necrosis of the femoral head occurred in 10.4% of patients. (5) The most satisfactory therapeutic results (almost 100% cured) are obtained when treatment begins during the first week of the child's life. PMID- 1934719 TI - Coxa vara infantum, hip growth disturbances, etiopathogenesis, and long-term results of treatment. AB - The literature concerning coxa vara infantum (CVI) contains only a few long-term follow-up reports of the treatment. This study was performed to define the clinical and roentgenographic features of coxa vara infantum (CVI) in children and skeletally mature patients. Special attention was given in follow-up evaluations to the growth and impairment of the hip joint (acetabulum, femoral head, and neck) before and after operative treatment in different age groups. Because in difficult cases the results of subtrochanteric osteotomy have not been satisfactory and have led to recurrences, the use of overcorrecting of the neck shaft angle value into valgus position has been adopted. To gain further insight into etiopathogenesis of CVI, histologic investigations were carried out. These investigations revealed growth and endochondral ossification disorders. Similar changes found in the growth zone of the iliac bone seem to indicate that the ossification disturbances are multifocal. Expansion of the fibrous connective and calluslike tissues is evidence of the overload syndrome in CVI. PMID- 1934720 TI - Long-term results of functional treatment in intraarticular knee fractures and multifragment fractures of the shaft of femurs. AB - Functional treatment of fractures is a nonoperative technique used in intraarticular knee fractures and multifragment and multilevel fractures of the shaft of femurs since 1974. The basic principle of this technique is placement of the fractured extremity in the specially designed rehabilitation splint, with skeletal traction fixed above the ankle joint through both tibia and fibula. Traction reduces the fracture while stretching of muscles provides conditions favorable for callus formation. Exercises are first isometric and then isotonic. During exercises, muscle tone and moments of force in each muscle group are measured to evaluate effects of exercises. Exercises in traction and rehabilitation splints are continued until clinical signs of healing are observed (i.e., for six to eight weeks with intraarticular knee fractures and ten to 12 weeks with fractures of the shaft of femur). Alternative flexion of bone fragments with their compression by the contracted muscles facilitate absorption of hemorrhage, reduces swelling, and accelerates osteogenesis by replacing passive-tissue congestion with the active-tissue metabolism. Seven hundred fifty seven intraarticular knee fractures with 76% excellent and good results, 20% average, and 4% poor were observed with this treatment. Functional treatment was also used in 320 multifragment and multilevel fractures of the shaft of femurs, with approximately 81% excellent and good results, 17% average, and 2% poor. Functional treatment of fractures is simple and safe, promotes healing, prevents muscle atrophy, reduces contracture formation, and minimizes functional loss. PMID- 1934721 TI - Limitations of radiography and computed tomography in the diagnosis of transverse sacral fracture from a high fall. A case report. AB - Transverse sacral fractures with sacral canal compression and neurologic deficit are rare sequelae of high falls. Nevertheless, a high index of suspicion is necessary as such an injury may present significant complications and may be missed on standard anteroposterior pelvic roentgenograms and pelvic computed tomography (CT) examinations obtained during the evaluation of multiple traumas. The saddle anesthesia, loss of bladder and sphincter function, and sexual dysfunction may be masked or unrecognized during the acute phase of polytrauma. Special attention must be directed to obtaining a lateral profile view of the sacrum, as this deformity may not be seen in any other view. Sagittal reconstruction images of the sacrum can be obtained during a pelvic CT examination if the initial lateral roentgenograms are technically inadequate because of the patient's obesity or limitations of portable radiographic equipment in the emergency department. The CT scoutview itself may show the acute sacral angulation if sufficient technique factors are employed. The roentgenographic suspicions can be confirmed with lateral multidirectional tomography or even with sagittal magnetic resonance imaging (MRI). Because this transverse sacral fracture is unstable in flexion, additional neurologic injury may result if the spine or hips are unwittingly manipulated in flexion. PMID- 1934722 TI - Cervical spine instability in rheumatoid patients having total hip or knee arthroplasty. AB - The records and roentgenographs of 113 rheumatoid patients treated by total hip or knee arthroplasty were analyzed retrospectively. The cervical spine roentgenographs were evaluated for significant atlantoaxial subluxation, atlantoaxial impaction, and subaxial subluxation. One or more of these findings were present in 69 (61%) of the patients. Thirty-five of the 69 (50%) with roentgenographically documented cervical spine instability had no signs or symptoms of instability at the time of admission for joint replacement. This high incidence of cervical spine instability in a select population of rheumatoid patients emphasizes the importance of preoperative evaluation of the cervical spine including flexion and extension lateral roentgenographs. PMID- 1934723 TI - Aortic rupture complicating a fracture of an ankylosed thoracic spine. A case report. AB - A 34-year-old man was injured in a motorcycle accident and suffered both aortic rupture and thoracic spinal fracture, complicated by an underlying undetected ankylosing spondylitis. The latter disease can affect the integrity of vascular and spinal structure. Aortography is recommended as a high priority for the patient in an unstable cardiovascular condition requiring a definitive diagnosis. Aortic rupture and thoracic spine fracture may occur from high energy deceleration trauma. Motor vehicle passenger and pedestrian injuries are most commonly involved, although airline accidents and high falls also generate some cases. Mediastinal widening, displacement of esophagus and trachea, apical dissection of blood, and, especially, paravertebral pleural space widening are common to both injuries. Whereas most mediastinal hematomas are nonaortic in origin, a combined injury must be considered because clinical features may also overlap. These include hypotension (hypovolemic or spinal shock), paraplegia, and severe back pain. In light of the high mortality and time constraints associated with aortic rupture, immediate diagnostic resolution is necessary for appropriate management and priority of investigation. PMID- 1934724 TI - Shoulder pain and functional disability in spinal cord injury patients. AB - Sixty spinal cord injured patients were examined to determine the incidence of nontraumatic shoulder pain and associated functional disability during the first 18 months after spinal cord injury (SCI). Seventy-eight percent of quadriplegics and 35% of paraplegics had pain in the first six months. When reexamined six to 18 months after SCI, 33% of the quadriplegics and 35% of the paraplegics continued to have pain. The functional disability resulting from shoulder pain was not a significant problem for the paraplegics; however, 84% of the quadriplegics having pain had either moderate or severe functional disability during the first six months after SCI, and this impairment persisted in patients with shoulder spasticity at follow-up evaluation between six and 18 months postinjury. PMID- 1934725 TI - Fate of frozen intercalary allograft at one year after implantation with adjuvant chemotherapy treatment. A case report. AB - The proximal humerus of a 21-year-old man was reconstructed with a frozen allograft combined with a Neer shoulder prosthesis. At graft retrieval one year later, the proximal end of the allograft had revascularized with some osteogenic activity, but distally neither vascular ingrowth nor osteogenic activity was seen. Allografts should not be used unsupported because of their potential weakness with time. Intramedullary stems should be used to support functional allografts which primarily facilitate soft-tissue reattachment. PMID- 1934726 TI - Controversy in anterior shoulder instability. AB - The main areas of controversy in anterior shoulder instability are acute dislocation, recurrent instability, pain and instability in the "throwing athlete", and the role of arthroscopy. Treatment of the acute dislocation involves rest initially, followed by aggressive rehabilitation with protection of the shoulder until strength and motion have returned and pain and apprehension have resolved. Patients with recurrent instability may be seen with a variety of clinical scenarios. The surgical indications, pathology, and two methods of soft tissue reconstruction are described along with an approach to postoperative rehabilitation. Return to sporting activity may be feasible by three months. The current thinking on the painful shoulder in the "throwing athlete" is outlined. Management must be based on an accurate diagnosis. Strengthening of the rotator cuff and scapular stabilizers is recommended with surgery to correct the pathology in those who fail this program. Arthroscopy is a valid tool in the diagnosis of anterior shoulder instability. The clinical significance of some intraarticular findings has not yet been clarified. Therapeutic use should be undertaken only in experienced hands, appreciating that failure of arthroscopic repair is higher than comparable open surgical techniques. The open approach to anterior stabilization is preferred. PMID- 1934727 TI - Transplantation of isolated chondrocytes. AB - Intramuscular transplantation of isolated syngeneic chondrocytes from hyaline and elastic cartilage results in formation of cartilage with various degrees of similarity to the original tissue. Cells from cartilage with a simple structure, such as nasal septal cartilage, form islands of tissue with flattened chondrocytes at the periphery and more rounded ones in the center. Chondrocytes from auricular (elastic) cartilage taken from young animals produce islands of tissue with an arrangement of cells and fibers similar to that of the material used for isolation of chondrocytes. Cartilage produced by elastic chondrocytes from older animals has an irregular arrangement of cells and contains fewer elastic fibers than cartilage produced by chondrocytes of corresponding age in situ. Chondrocytes from epiphyseal cartilage produce tissue with an irregular arrangement of cells, but nevertheless, are treated with endochondral ossification. Transplants of allogeneic chondrocytes evoke a strong immune response in the recipient. Such chondrocytes produce cartilage that is surrounded and slowly resorbed by infiltrating cells and does not ossify. Short-term immunosuppression (procarbazine and antithymocyte serum) prevents rejection of such cartilage and allows endochondral ossification. PMID- 1934728 TI - Varus rotational femoral osteotomies in adults with hip dysplasia. AB - Fifty-six hips in 48 consecutive patients operated on for congenital dysplasia of the hip during the years 1971 through 1986 were evaluated for an average follow up period of nine years (range, two-21 years). Twenty-three percent of the patients were treated with revision to total hip arthroplasty by the time of follow-up examination. The average time before revision was 8.6 years. All but three of the remaining hips were rated good or excellent (72%). These patients tended to have minimal or no preoperative degenerative joint disease. Complications included one subtrochanteric fracture, two cases of loss of fixation, and one superficial wound infection. The authors conclude that the operation provides predictable, high-quality results in those patients with minimal or no degenerative changes preoperatively. In those patients with mild or moderate degenerative changes, it may forestall the onset of severe symptoms by several years. PMID- 1934729 TI - Vibration arthrometry in congenital dislocation of the hip. AB - Three hundred six neonates referred to a research clinic for vibration arthrometry were studied to determine whether the application of objective methods could enhance the accuracy of hip examinations. A total of 629 vibration episodes (hip "clicks" and "clunks") were detected using miniature accelerometers and recorded during testing for congenital dislocation of the hip. Five categories of congenital dislocations of the hip (CDH) were defined: normal (53 cases), safe click (201 cases), click associated with later CDH (16 cases), unstable (14 cases), and late CDH (22 cases). Follow-up examinations were performed over a four-year period. Detailed measurement of vibration signals was possible and resulted in the resolution of eight variables for each episode. Two variables, pulse area and peak frequency, were selected for their power to discriminate between the five clinical groups. The pulse area values were higher for the late and unstable groups. In addition, the vibrations were examined using Fourier analysis, and the safe click group demonstrated higher frequency components than any other group. Vibration arthrometry is proposed as a possible adjunct in screening for CDH, as it may pick up cases that would be missed by an average examiner and it could monitor clicks, thus avoiding nonessential splintage. PMID- 1934730 TI - Longitudinal crack propagation in bone around femoral prosthesis. AB - Intraoperative femoral fracture is a well-recognized technical complication of cementless total hip arthroplasty. This study was designed to establish an in vitro model for initiation and propagation of fractures of the proximal femur in cementless THA and to assess the effect of fracture fixation in the form of cerclage wiring and drilling a hole in the distal extent of the fracture line. Fourteen human anatomic femur specimens were studied. Longitudinal cracks were made and propagation was performed on a materials testing system machine. A drill hole at the tip of a longitudinal crack does not prevent crack propagation. However, cerclage wiring has a statistically significant effect (p less than 0.025) on the ability of the fractured femur to withstand increased load. PMID- 1934731 TI - Resection arthroplasty for septic arthritis of the hip in ambulatory and nonambulatory adult patients. AB - Twenty-three patients who required resection arthroplasty because of pyogenic infection of a hip joint were reviewed. Nine of the patients were ambulatory, and the others were either paraplegic or bed-ridden because of chronic neurologic disease. The average duration of symptoms was more than two months. The only consistently abnormal laboratory test was the erythrocyte sedimentation rate (ESR). Joint-space narrowing and bone erosion due to osteomyelitis were the most common roentgenographic findings. Different microorganisms were isolated from the different cases, but Staphylococcus aureus was documented in eight hips. Femoral head dislocation of subluxation was documented in 11 of 24 hips. Osteoarthrosis or osteonecrosis was a preexisting condition in only four hips, all in ambulatory patients. Pathologic findings included loss of articular cartilage by surface erosion and by subchondral bone resorption, resulting in the separation of the cartilage from the underlying bone, bone erosion, osteomyelitis, and segmental osteonecrosis. PMID- 1934732 TI - Factors influencing long-term results in high tibial osteotomy. AB - Recorded here is a comprehensive review of the current literature on high tibial osteotomy with emphasis on postponing an inevitable total knee arthroplasty (TKA). Accompanying this review is a confirmatory, retrospective study of 35 patients with 39 high tibial osteotomies with an average follow-up study of 8.5 years (range, 3.8-15.1 years). Twenty-two of the patients (57%) had good results, seven (18%) fair, and ten (25%) poor at final follow-up examination. Nine of the 35 patients required TKA at an average of 4.7 years post-osteotomy. The percentage of good results diminished with time of follow-up study, starting at two years with 87% good results and ending at 15 years with only 57% of the patients remaining in that category. Patients lost an average of 8 degrees of flexion post-osteotomy, regardless of good, fair, or poor result. Patients with favorable results were usually younger than 60 years of age, and had less than 12 degrees of angular deformity, pure unicompartmental disease, ligamentous stability, and a preoperative range of motion are of at least 90 degrees. PMID- 1934733 TI - Dissociation of the tibial component in total knee replacements. AB - Dissociation of the polyethylene component from its metal backing in total knee arthroplasty is a recognized problem regarding the patella. Two cases of dissociation of the metal-backed tibial component from its polyethylene articulating surface presented symptoms of prosthesis failure: persistent pain, swelling, sensations of instability, and gait difficulty. Investigations ruled out prosthesis malalignment, loosening, and sepsis. Precise diagnosis of dissociation of the tibial component was made by diagnostic arthroscopy. PMID- 1934734 TI - Acute osteomyelitis of the patella 50 years after a knee fusion for septic arthritis. A case report. AB - Nontraumatic, hematogenous osteomyelitis of an unfused patella occurred in a 62 year-old female patient, 50 years after septic arthritis of the knee was treated in childhood by femorotibial fusion. This extremely rare condition was successfully treated by a patellectomy, continuous irrigation, and antibiotics. This occurrence seems not to have been reported previously in English literature. PMID- 1934735 TI - Measurement of tibial torsion and thigh-foot angle using goniometry and computed tomography. AB - Three therapists measured tibiofibular torsion and thigh-foot angle (TFA) goniometrically in 17 normal subjects, aged three to 24 years. Tibiofibular torsion was also measured using computed tomography (CT). Differences between testers for the goniometric measures were analyzed using a nonparametric analysis of variance. Wilcoxon's rank sum test was used to determine differences between goniometric and CT measures for tibiofibular torsion. No significant difference for goniometric measures was found between testers for tibiofibular torsion or TFA. A significant difference averaging 5 degrees between goniometric and CT torsion measures was found between testers. Although a significant difference was found between the two measurement methods, the degree of difference may not represent a significant clinical difference, as a range at 5 degrees is commonly reported as the margin of error for goniometric measurements. PMID- 1934737 TI - Peroneal muscle function in chronically unstable ankles. A prospective preoperative and postoperative electromyographic study. AB - In 33 patients with unilateral chronic ankle instability, peroneal muscle function was evaluated by surface electromyography (EMG) pre- and postoperatively. Twenty-six patients had a static reconstruction using the whole peroneus brevis tendon and seven patients had a dynamic one using only the anterior half of the tendon. At plantar flexion the peroneal EMG activity was markedly higher in men than in women, otherwise there were no differences between the sexes. Neither pre- nor postoperatively were there any significant differences between the patients' healthy and diseased legs. Postoperatively and after physiotherapy, there was a significant increased peroneal activity in both legs of the patients. The peroneal EMG activity was increased after operation, although the type of operation seemed to make no difference. A difference between the two types of reconstructions could only be shown at dorsal flexion, with the higher response in the dynamic reconstructed patients, because of the existing tension elicited of the remaining intact half tendon. This difference is probably not important for peroneal muscle function. Peroneal neuromuscular integrity was intact and independent of preoperative instability and the method of reconstruction. PMID- 1934736 TI - Hallux valgus repair. DuVries modified McBride procedure. AB - The DuVries modification of the McBride procedure was investigated in 72 feet in 47 patients with hallux valgus deformity. Overall, the patient satisfaction rate was 92%. The hallux valgus averaged 32 degrees preoperatively, and 16 degrees postoperatively. The intermetatarsal angle averaged 14 degrees preoperatively and 9 degrees postoperatively. Anatomic realignment of the remaining tibial sesamoid was achieved in 28% of the feet. As a result of realignment of the first metatarsophalangeal joint, the intractable plantar keratosis beneath the second metatarsal head was resolved in 19 of 20 feet. Six patients developed a hallux varus deformity that averaged 7.5 degrees. All cases of hallux varus had medial displacement of the tibial sesamoid. The number of patients who could withstand unrestricted shoe wear increased from ten patients preoperatively to 30 patients postoperatively. The patient activity level increased in two thirds of the cases. The distal soft-tissue procedure produces the most predictable correction in patients with a hallux valgus deformity measuring less than 30 degrees. In more severe deformities, a proximal metatarsal osteotomy should be added to the procedure. PMID- 1934738 TI - Hinged silastic implants of the great toe. AB - Since 1982, hinged silastic implants have been used in the treatment of hallux valgus and hallux rigidus in preference to excision arthroplasty or metatarsophalangeal joint fusion. The results of this treatment in 106 feet in 89 patients are satisfactory to subjective and objective assessment over an average follow-up period of 27.7 months (range, 12-60 months). Hinged prosthesis overcomes the problems associated with resection arthroplasty. PMID- 1934739 TI - Lower limb-length discrepancy. An epidemiologic study. AB - Two retrospective epidemiologic studies have examined the incidence and prevalence of significant lower limb-length discrepancy and the number of surgical corrections by lengthening in 1987 in France. The incidence of apparatus prescriptions for asymmetry correction filled was 2.16 per 100,000 population. The prevalence of people using a corrective apparatus was one per 1000 population. The male-to-female ratio was 1.95:1. Because of biases in the study population, the actual incidence and prevalence of significant limb-length discrepancies is likely to be considerably higher. A questionnaire administered to surgeons of the French Orthopedic Society revealed that the majority of surgical lengthenings were performed by large orthopedic teams. In the 418 procedures reported, the tibia was lengthened more often than the femur (ratio 1.1:1). Gradual distraction techniques were used in 89.4% of cases, with the Ilizarov apparatus used in 57.4%, the Wagner apparatus in 20.6%, and the Orthofix fixator in 11.2%. Immediate distraction techniques were used in 7.9% of cases, 85% of which were done on the femur. Average total lengthening was 51 mm for tibia and femur. Average lengthening was greater for methods of gradual distraction (53.5 mm) than for immediate distraction (31.4 mm). PMID- 1934740 TI - Premature partial physeal arrest. Diagnosis by magnetic resonance imaging in two cases. AB - The management of premature physeal arrest requires accurate assessment of not only the location but also the extent of the bar. Numerous imaging techniques are available to evaluate the physis. Multiplanar tomography has proven to be the most precise method. The utility of magnetic resonance imaging (MRI) of physeal bars has not been demonstrated. This article presents MRI results in two cases of physeal bars. MRI provides a means of assessing physeal bar formation with an accuracy approaching that of multiplanar tomography. In certain instances, its efficacy may exceed that of tomography, specifically when the physis cannot be properly oriented for tomographic evaluation, when more planes are desired, and when radiation exposure is thought to be excessive. With improvement of its capabilities and availability (which may also reduce cost), it may become the diagnostic imaging technique of choice. PMID- 1934741 TI - Extravasation injuries in the upper extremity. AB - Fourteen patients with intravenous extravasations of chemotherapeutic medications, radiographic contrast agents, vasopressors, fluorescein, or albumin/potassium phosphate were evaluated with regard to function and cosmesis. The average follow-up period was 8.4 months (range, one-24 months). Five patients initially were managed conservatively and, after demarcation of the necrotic area, had surgical procedures for skin coverage. Four of these patients had poor functional and cosmetic results. The remaining patient had an excellent final result. Because of the generally poor results observed in the aforementioned patients, a program of early recognition and surgical intervention in selected extravasation cases was instituted. Following this change, eight of nine patients had good or excellent results. Early surgical involvement in the evaluation of extravasations, with and early surgical drainage and irrigation in selected severe cases, appears to improve the outcome of these iatrogenic injuries. PMID- 1934742 TI - The effect of biphosphonate on induced heterotopic bone. AB - HEBP (1-hydroxy, ethylidene-1, 1-biphosphonate) inhibited mineralization and was observed in matrix-induced heterotopic bone in rabbits. In one group of rabbits, HEBP was administered continuously until sacrifice 20 weeks after the operation. Another group of animals received HEBP for the first four weeks only. The effect of HEBP on de novo bone formation was determined by histologic and biochemical analyses. Implant alkaline and acid phosphatase levels and implant calcium and phosphate contents were measured. The implants of HEBP-treated animals showed diminished implant resorption and, at the same time, formation of atypical osteoid tissue. Quantitative measurements revealed a decrease of acid phosphatase activity, whereas implant alkaline phosphatase activity was unaffected. The mineralization, as depicted by the implant calcium and phosphate content, was almost completely inhibited during HEBP-administration. These effects were completely reversible after the withdrawal of the drug. Remineralization began directly after discontinuation, and recovered only 12 weeks later. The results of this study confirm reports that HEBP cannot prevent the formation of heterotopic ossification. The only effect would be a delay of mineralization during its administration. PMID- 1934743 TI - A comparison of the healing properties of rabbit Achilles tendon injuries at different levels. AB - Rabbit Achilles tendons were transsected at the muscle-tendon junction (Group 1), midtendon (Group 2), or at the calcaneus insertion (Group 3). Treatment consisted of immobilization in a long leg cast without surgical repair. The contralateral leg served as a control. Tensile testing was performed at four weeks. Groups 1 and 2 failed most often in the proximal muscle rather than at the healing site. In contrast, Group 3 failed more often at the healing site than in the muscle and was statistically superior to Groups 1 and 2 with respect to strength and stiffness. Statistically, control specimens showed failure at the musculotendinous junction at greater loads and were stiff compared to the experimental groups. PMID- 1934744 TI - Mechanical properties of bone cement. Importance of the mixing technique. AB - The compressive and shear strength and the modulus of elasticity were studied in three different bone cements (CMW, Simplex P, and Zimmer low-viscosity cement). One hundred four specimens were prepared by either a conventional manual mixing technique or mechanical vibration. Mechanical mixing gave a significant increase in shear strength for CMW and Simplex P. The compressive strength of Simplex P and Zimmer low-viscosity cement was significantly improved by mechanical mixing. The scatter of the results was significantly reduced by mechanical mixing. The modulus of elasticity was significantly increased by mechanical mixing for the three cements. The uniformity of the bone cement mass seems to be increased by a standardized mechanical mixing technique. PMID- 1934745 TI - Ultrastructural differences between the cells of the medical collateral and the anterior cruciate ligaments. AB - The anterior cruciate ligament (ACL) does not heal after an interstitial tear, in contrast to the medial collateral ligament (MCL), whose interstitial tears heal readily. The light microscopic and ultrastructural differences between the cells of the two ligaments were studied in rabbit knees to observe the healing characteristics of the two ligaments. A rabbit knee was chosen because the rabbit ACL, like that of humans, does not heal following interstitial injury. The cells populating the MCL have the characteristics of fibroblasts. The cells of the ACL resemble fibrocartilage cells. The phenotypic differences in the cells of the two ligaments may be important determinants of the differences in healing. PMID- 1934746 TI - Nucleolar organizer regions in bone tumors. AB - Silver-stained nucleolar proteins (AgNORs) were counted in a variety of bone tumors. In osteosarcomas, the number of AgNORs was also quantified before and after chemotherapy. Malignant bone tumor cells possessed more than five small AgNORs (5.85 +/- 1.39). Nuclei of benign bone tumor cells had less than three (2.61 +/- 0.51). A significant difference in the number of AgNORs between osteosarcomas before chemotherapy (6.10 +/- 1.22) and after chemotherapy (4.20 +/ 1.07) was observed. (p less than 0.001). The number of AgNORs in osteosarcoma patients with better prognoses was smaller than that of osteosarcoma patients showing poor prognoses, but without significant difference. The results of the present study indicate that the AgNOR count might help in determining malignancy, evaluating the effect of chemotherapy, and deciding the prognosis. PMID- 1934747 TI - Interaction of allogeneic demineralized bone matrix and porous hydroxyapatite bioceramics in lumbar interbody fusion in rabbits. AB - Bone repair by autograft is effective in clinical practice. However, serious problems arise when a considerable volume of transplant is needed, as with spinal fusion procedures. The use of bone substitutes combined with osteoinductive agents may contribute to the solution of such problems. In this study, the effectiveness of such a procedure was tested in an experimental model of interbody fusion in rabbits in which the incorporation of a porous hydroxyapatite block (HA) was enhanced by the addition of allogeneic demineralized bone matrix (DBM). The latter was used as a delivery system for the osteoinductive activity of the bone morphogenetic protein contained in the matrix. A group implanted with combined HA + DBM showed significantly earlier stabilization of the fusion when compared to groups implanted with DBM alone, HA alone, and bone autografts. On the other hand, the general results of the fusion with HA + DBM were superimposable on those of autografts. With further research, the combination of a bone substitute and an osteoinductive agent may constitute an alternative to the use of bone autografts. PMID- 1934748 TI - Dynamic spine alloplasty (spring-loading corrective devices) after fracture and spinal cord injury. 1977. PMID- 1934749 TI - The effect of indomethacin on Achilles tendon healing in rabbits. AB - In a randomized, blind study, percutaneous tenotomy was performed on the right Achilles tendon complex of 32 male, New Zealand rabbits. The rabbits were placed in long-leg casts to approximate the tendon. Sixteen rabbits received oral therapeutic doses (1.5 mg/kg/day) of indomethacin elixir; the remaining 16 rabbits received no medication and comprised the control group. At two and six weeks following tenotomy, eight rabbits in each group were sacrificed and the Achilles tendon complexes were resected. Each tendon was evaluated for tensile force-to-failure by uniaxial tensile loading using an Instron Materials Testing Machine at a velocity of 0.85 cm/second. Histologic evaluation assigned the specimens to categories of either "relatively mature" or "relatively immature," based on the degree of cellularity, neovascularity, and collagen orientation that had occurred in the healing process. The mean force-to-failure two weeks post tenotomy for the experimental group was 75.7 +/- 42.3 Newtons (N), and 96.6 +/- 35.2 N for the control group; at six weeks post-tenotomy, the mean force-to failure for the experimental group was 165.5 +/- 34.3 N and 160.2 +/- 31.6 N for the control group. Statistical analysis revealed no significant differences in tensile force-to-failure or histologic appearance between the experimental and control groups at either time interval. These results suggest that indomethacin, and potentially other nonsteroidal antiinflammatory drugs, may be used in conjunction with a tendon injury without significantly affecting the early healing process. PMID- 1934750 TI - Therapeutic effects of transplantation of lyophilized and radiation-sterilized, allogeneic bone. AB - Lyophilized radiation-sterilized bone graft operations were analyzed according to 27 variables in 1014 patients with two-year follow-up results. In 91.3% of patients, the result of treatment was "very good" (full-health restoration) or "satisfactory" (restoration with some small disorders). In 5.1%, the results were unsatisfactory. There was no clear association between the results of treatment and the patient's age. A definite correlation was found in preoperative diagnosis and end results. Better results were achieved in benign tumors and congenital malformations than in post-traumatic and degenerative conditions. Preferred anatomic host beds for transplantation were the coxa, arm, and vertebral column. Less satisfactory results were found in the leg and forearm. The number of good results of treatment declined with increasing duration of preoperative or chronic illness and with increasing postoperation time. Supplementary autogeneic bone did not seem to improve the end result. Concomitant disease was not always a contraindication for bone graft surgery. The significance of various traits in analysis of the final "result of treatment," "fitness for work," and "role of the graft" was evaluated with the aid of Pearson's indices of coincidence. PMID- 1934751 TI - The results of surgical treatment of primary spinal tumors. AB - A series of 72 primary spinal tumors including 57 malignant and 15 benign ones were treated surgically from the years 1961 to 1987. Neurologic complications developed in 52 patients, with paraplegia in 20, spastic paraparesis in 19, cauda damage in 11, and brachial plexus injury in two cases. The principles of the treatment were excision of the tumor, decompression of nervous elements, and stabilization of the spine. Surgical treatment was supplemented with radiotherapy or chemotherapy, or both. In the group of benign tumors, no deaths occurred and the clinical results were good. The results obtained in the group of malignant neoplasms were evaluated according to survival time and were analyzed separately for the dying and the surviving patients. In this group of 57 patients, 42 died, 17 dying within one year (three died from postoperative complications). In the remaining 25 patients surviving over one year, the mean survival time was four years and four months. Fifteen patients are alive, and their mean survival is five years and three months. The neurologic results in 39 patients surviving over six months were good in 92.3% of cases. Regression, or significant improvement of neurologic disturbances, was of considerable importance for the survival time. At the present time, surgical treatment combined with radiotherapy and chemotherapy is the most favorable method for the treatment of primary spinal tumors. PMID- 1934753 TI - Zespol. An original method of stable osteosynthesis. AB - Poor clinical results with autocompression plates and six years of biochemical investigations, have led to the conclusion that a plate should not be tightened directly to a bone. Consequently, in 1979, platform screws and special autocompression plates were invented. These were later developed into the original system of stable osteosynthesis called Zespol. The system consists of a plate, platform screws, and nuts that together form a small clamp fixator. The Zespol system enables a surgeon to perform compression, neutralization (protecting) contact, and bridging osteosynthesis. In all types of osteosynthesis, the Zespol fixator can be used either internally or externally. From June 1982 through December 1988, Zespol was applied in 1295 osteosyntheses (850 fractures and 445 pseudoarthroses). The average healing time of fractures was 18 weeks, and in cases of nonunions, 21 weeks. Second operations were required in 5.1% of cases, generally with good or fair results. The overall final results were 97.9% good and fair, and 2.1% poor. PMID- 1934752 TI - Pyogenic infection of the spine. AB - In a review of 442 patients in all age groups with pyogenic infection of the spine, the disease seldom involved one vertebra, as usually two or more vertebral bodies were affected. Most frequently the lumbar spine was involved, next most frequently thoracic, then cervical spine. The sacrum rarely was involved. In 219 patients the onset of the disease was acute, in 147 subacute, and in 76 mild. In the initial period of the majority of cases, the disease was misdiagnosed. Consequently, only a small proportion of these patients were referred to the authors' department in the early stage. The patients presented a great diversity of pathologic features, clinical manifestations, and various complications. There were 53 cases of fistulae, 25 cases of hypostatic abscess, eight cases of meningitis, five cases of flaccid paralysis, 12 cases of spastic paresis, three patients with paresis of the upper extremities, and three with paresis caused by cauda damage. There were 295 cases treated conservatively and 147 by operation. Conservative treatment was applied in mild cases, which were cases diagnosed with certainty and without complications. Surgical treatment was applied in severe, rapidly progressive, complicated cases, and in patients with involvement of the nervous system. The good and satisfactory results in both groups were very similar, consisting of about 98%. The percent of good results was 4.3% higher in the surgically treated patients. Also, neurologic results after operative treatment were very favorable. These results show that when the indications are properly established, both conservative and operative methods will give good and satisfactory results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934754 TI - Late results of treatment in Perthes' disease by a functional method. AB - Two hundred ninety-six cases of Perthes' disease with 334 affected hips (38 children had bilateral involvement) were treated by the principle of containment in a "broomstick cast" in abduction and internal rotation, preserved motion in the hip, and continuous traction. Prognostic indicators were recorded, including the age at the onset of the disease, Catterall Group, and risk factors. The mean follow-up period was 8.6 years. The average age at the last examination was 14.1 years (range, six to 25 years). The end results of the treatment were evaluated roentgenographically by the Heyman and Herndon method of quotients. In these 334 treated hips, the results were very good in 216 cases and good in 92 cases (92% very good and good combined), whereas in 23 cases, results were fair and in three, poor (8% fair and poor combined). The results were dependent on the age at the time of diagnosis, the degree of femoral head involvement, and presence of "head at risk," particularly femoral subluxation. The fair and poor results were found in children older than nine years of age, with total head involvement, crushing epiphysis, and presence of risk factors. The results in this study suggest the superiority of treatment in Perthes' disease by a functional method in comparison with the results of treatment by orthosis or femoral osteotomy. This method shortened considerably the time of treatment; the average time was 13 months. PMID- 1934755 TI - Bone histogenesis mediated by nonosteogenic cells. AB - Intramuscular implantation of several established, nonfibroblastic epithelial cell lines of various origin causes endochondral ossification at the site of cell graft. Heterotopically-induced bone is also a site of myelopoiesis. Myelohistograms of ectopic bone marrow do not differ substantially from that of marrow present in orthotopic (skeletal) bones. Heterotopically-induced bones are not covered by a periosteal membrane with a functioning cambium layer. The nature of the bone-inducing principle of epithelial cells is not known as yet, although it was established that cells able to induce heterotopic bone formation are characterized by a high alkaline-phosphatase activity and have an epithelial status. Cells responding to the osteoinducing principle are distributed among skeletal muscles and are absent in the peritoneal cavity or in the kidney parenchyma. Periosteal membranes of skeletal bones are activated by a variety of agents (Moloney sarcoma virus-induced tumors, numerous nonvirus-induced neoplasms, T-lymphocyte mitogens, and activated lymphocytes) to proliferate and lay down new bone. The same agents can also activate in vivo perichondral membranes. It is theorized that cells involved in antitumor reaction produce a chondroblast/osteoblast activating factor(s), in addition to the osteoclast activating one. PMID- 1934756 TI - The efficacy of application of lyophilized, radiation-sterilized bone graft in orthopedic surgery. AB - The purpose of this study is retrospective analysis of clinical application of lyophilized (freeze-dried), radiation-sterilized allografts in various orthopedic disorders. Grafts of this type have been produced by Polish tissue banks for many years, even before the production of deep-frozen grafts was started. This type of graft is still produced because of their easy storage, transportation, and distribution. Their application is successful in selected cases. Freeze-dried, radiation-sterilized cancellous or cortical-cancellous blocks, cancellous chips, or diaphyseal cortical struts were applied in 435 patients ranging from three to 74 years old. There were five main groups of procedures: posterior or anterior spine fusion, 224 cases; joint arthrodeses, 36 cases; reconstructive operations, 83 cases; filling of bone lesions, 59 cases; and posttraumatic reconstructive operations, 33 cases. The efficacy of application of lyophilized, radiation sterilized allografts was estimated retrospectively on the basis of physical examination data and roentgenographic assessment collected during postoperative visits. Incorporation and rebuilding of the grafts as well as a satisfactory therapeutic effect were achieved in 394 (91%) patients. Excluding the cases of congenital and hypovascular pseudoarthroses, post-osteomyelitis gap and focuses, as well as Stage 2 bone lesions, it is suggested that lyophilized, radiation sterilized allografts can be applied on the condition that intimate contact between the donor bone and host bed is complete and sustained. PMID- 1934757 TI - Porous and porous-compact ceramics in orthopedics. AB - A bioceramic material has been obtained by a group of researchers with the collaboration of bone surgeons and veterinary doctors. This material has the following properties: chemical composition, 97% Al2O3, 2.5% MgO, and 0.5% CaO; mineral composition, alpha-Al2O3 corundum, MgAl2O4 spinel; open porosity, 70-80%; pore diameter, more than 90% of pores between 100 and 800 microns; bending strength, approximately 15 MPa. Experiments performed on rats, rabbits, and sheep demonstrated good biocompatibility with the material implanted in their bone tissue. The outer and the inner pores were filled with the healthy bone tissue adherent to the ceramic material, and a strong biologic bond was created. The material penetrated by this mineralized bone tissue increased its mechanical strength by about 70%. These properties of the material may encourage its application to bone surgery. The porous ceramics were implanted in the bones of more than 200 patients. Observations revealed that the process of bone tissue ingrowth into the pores of material had been accomplished in two to three months. The application of the material included filling the bone cysts, postsurgical or trauma-related bone defects, destroyed vertebra caused by the removal of bone tumors, and in the alloplasty of the hip joint. A modification of the ceramic material described above has been developed: a porous-compact ceramic material that is integrally bonded and has mechanical strength several times greater than the porous one. It also enables the biologic connection with the bone. This type of material has been used for filling the dome of the acetabulum in the "coxa protrusa" and in the alloplasties of the hip joint. PMID- 1934758 TI - Anterior operations in cervicarthrosis and vertebral artery compression. AB - Pain in the cervical spine in the course of degenerative changes is a frequent complaint reported by patients seeking the help of various specialists. Depending on the location of pathologic changes, the pain in the spine may be accompanied by a whole array of signs and symptoms, which are sometimes more troublesome for the patient than the back pain itself. The symptoms are sometimes so persistent and difficult to treat that they lead the patient to apathy and depression, even to the point of suicidal attempts. Should serious aggravation of symptoms develop despite all efforts at successful conservative therapy, surgical treatment is employed to remove the osteophytes protruding into the lumen of the vertebral canal and compressing the spinal roots. An analysis from 1969 to 1988 of treatment in 237 patients with neurologic disorders and concomitant or dominant disturbances of blood flow in vertebral arteries showed that there are specific indications for surgical decompression of the arteries, i.e., when lumen is constricted by the osteophytes at the level of uncovertebral joints. In a series of 47 patients, 42 cases were found to be pain free. PMID- 1934759 TI - [Clinico-pathological comparative study between brainstem encephalitis of Iizuka type and neuro-Behcet's disease]. AB - We experienced one necropsy case of brainstem encephalitis of Iizuka type (BSE) and one necropsy case of the brain-stem syndrome (BSS) of typical neuro-Behcet's disease, and compared them clinically and neuropathologically. Clinically both of these cases showed chronic progressive mental disturbance, pseudobulbar paresis, spastic tetraparesis, cerebrospinal fluid pleocytosis, increased protein, and brainstem atrophy observed by X-CT. Neuropathologically, irregular, boundary indistinct demyelinating lesions and obsolete softening lesions were sporadically found, associated with perivascular lymphocytic infiltration and gliosis centering on the brainstem. In this way, both cases were similar in many points except for the presence or absence of cutaneo-muco-ocular signs specific for Behcet's disease. Also BSE and BSS reports in the literature showed that both diseases were similar not only in clinical findings consisting of mental disturbance and brainstem signs but also in neuropathological findings with similar topographical distribution of the same histopathological changes, including the variations and diversity of these characteristics. Especially of much interest is their similarity in characteristic mental disturbance. In discriminating BSE from multiple sclerosis and other diseases with exclusive involvement of the brainstem, it is important to understand their clinical characteristics. The characteristic mental disturbance includes damage to memory and sentiment, a change in personality, and lowering in spontaneity, but calculation ability and orientation are comparatively preserved. Of course the similarity in clinical and neuropathological findings does not necessarily mean the identical etiopathogenesis. However, it is possible to consider that neuro Behcet's disease (syndrome) may form a wide spectrum with BSE and typical neuro Behcet's disease at the both ends, regarding the time and spatial diversity of the appearance of cutaneo-muco-ocular signs. PMID- 1934760 TI - [Releasing phenomenon of well learned praxis with right hand]. AB - We report a case with "releasing phenomenon of well learned praxis" with right hand caused by cerebral infarction in the territory of left anterior cerebral artery. A 71-year-old right-handed woman suddenly developed motor paralysis in right lower and upper limbs associated with mutism. Motor paralysis of the right upper limb and speech disturbance improved gradually. At this period it was noted that she grasped and used an object in front of her with right hand against her own will. The neurological findings about one month after the onset of the disease revealed very mild weakness of the right upper extremity and severe motor paralysis of the right lower limb. In addition, tendon reflex was exaggerated in the right lower limb and sensory disturbance was noted in the region distal from the right knee. Neuropsychologically, ideomotor apraxia was observed in the left hand. Pathological gasping of the right hand was also noted. When the patient saw and touched an object, she used it with her right hand against her own will, and her left hand voluntarily hindered the right hand. This behavior is apparently similar with the "compulsive manipulation of tools" reported previously. However, the following hitherto unknown phenomena were observed in the present patient: Her right hand performed pantomimic movement for the use of objects orally described by the examiner without visually presenting them. The right hand also tended to imitate the gestures of the examiner automatically, even if the patient was not asked for imitating the gestures. These behavioral abnormalities of the right hand was thought to be liberated from the inhibition system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934761 TI - [Neuroradiological analysis of small infarcts in deep subcortical structure detected by CT]. AB - We studied angiographic findings of 56 patients who were diagnosed as lacunar infarcts in the basal ganglia or deep subcortical white matter based on clinical symptomatology and brain computed tomography. In 26 patients with CT lesions less than 15 mm in diameter, only eight (31%) showed minor angiographic findings. In 30 patients with lesion of 15 mm or more, however, 22 (73%) had abnormal angiographic findings. Fourteen of the 22 patients had minor irregularities, three had 25-75% stenosis, five had 75% less than stenosis at the bifurcation of the common carotid artery or the horizontal portion of the middle cerebral artery. Our findings support the notion that a small lesion on CT can result from an occlusion of the perforating artery itself and a larger lesion is much related to the major vessel or heart diseases, i.e., emboli from the parent artery or heart, obstruction of perforators at their origin by an atheromatous plaque of the horizontal portion of the middle cerebral artery, or terminal zone infarct due to hemodynamically significant stenotic lesion. In patients with a larger deep infarct on CT, further investigation of the arteries in the carotid-axis and heart is important for determination of therapeutic indication. PMID- 1934763 TI - [Slowly progressive fluent aphasia--clinical features and an imaging study including MRI, SPECT and PET]. AB - Three cases of slowly progressive fluent aphasia were presented. In all it began with word amnesia or stuttering, and in one to five years impairment of auditory comprehension, and reading and writing difficulties with kanji (Japanese morphograms) appeared. The neuropsychological and radiological findings were as follows: Case 1: a right-handed 65-year-old man showed severe fluent aphasia (the Western Aphasia Battery profile was rated as corresponding to Wernicke's aphasia but his score on the Token test was too high for Wernicke's aphasia) and memory disturbance. Cortical atrophy was prominent in the left temporal and parietal lobes. Hypoperfusion was evident in the bilateral anterior temporal region, suggesting the diagnosis of Pick's disease. Case 2: a right-handed 42-year-old man presented amnesic aphasia with buccofacial and ideomotor apraxia. The left frontal, temporal and parietal lobes were all atrophic. Hypoperfusion was marked in the left perisylvian and temporo-parietal regions, being similar to the pattern of Mesulam's slowly progressive aphasia. Case 3: a right-handed 55-year old man with amnesic aphasia. Left-side dominant cortical atrophy involved the frontal, temporal and parietal lobes. The metabolic rate was lower in the left anterior temporal lobe, compatible with the finding in Pick's disease. The common clinical features of these patients were selective deficits in vocabulary, resulting in impairment of confrontation naming, and auditory comprehension. They sometimes could not recognize things even when they were told their names; case 1 could not even point to objects on command, while their syntactic comprehension was well preserved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934762 TI - [Study of antibodies to motor end-plate in ocular myasthenia gravis]. AB - This study was undertaken to investigate whether serum obtained from ocular MG with undetectable antibodies contains antibodies which bind to normal motor end plates immunohistochemically. Nineteen patients with ocular MG were studied. Anti AChR antibodies in serum were assayed by an immunoprecipitation method using human junctional AChR as the antigen. Anti-AChR antibodies in serum which bind to the junctional AChR at the motor end-plates were detected immunohistochemically by incubating the muscle with each serum. Bound IgG was detected by peroxidase labeled protein A (P-PA). IgG deposit at the own limb muscle motor end-plates (biceps brachii) was also detected by P-PA. Anti-AChR antibodies in serum were positive in 9 out of 19 patients and IgG antibodies bound to the junctional AChR were demonstrated in 16 of 19 patients. IgG bound to own end-plates was observed in 13 of 14 patients studied. In 2 patients IgG was detected at the own end plates, but not at the not-self end-plates. These findings indicate that detection of IgG at the limb muscle end-plates serves for the diagnosis of ocular MG with undetectable antibodies in serum and anti-AChR antibodies in some patients may react exclusively with the autologous AChR. PMID- 1934764 TI - [Nationwide survey of necrotizing myelopathy associated with malignancy in Japan]. AB - Twenty-two cases of transverse myelopathy associated with malignancy were collected in nationwide survey in Japan. Paraneoplastic necrotizing myelopathy (PNM) was suspected in 9 of them and 8 cases were diagnosed as radiation myelopathy (RM), clinically and pathologically. Other 5 cases had different causes of transverse myelopathy. In comparison with PNM and RM, malignant lymphoma, flaccid paraplegia and sphincter dysfunction were highly associated in the patients with PNM. On the other hand, lung cancer, spastic paraplegia, abnormality in spinal MRI and dysesthesia in legs as an initial symptom were prevalent in the cases of RM. Six cases of them were compared pathologically. Although all cases had no metastasis of malignant cells, five cases of PMN showed acute and chronic necrosis and rarefaction of spinal cord with or without perivascular cuffing. One case of RM had focal spinal cord atrophy and no lymphocytes infiltration. Immunohistochemically, herpes simplex virus type 2 (HSV2) infection in spinal cord was shown in the 2 cases of the necrotizing myelopathy. Virus infection such as HSV2 could be one of causes of PNM and virological study must be done in the cases of necrotizing myelopathy associated with malignancy. PMID- 1934765 TI - [A case of acute water intoxication showing triphasic waves on EEG]. AB - We reported a case of acute water intoxication from compulsive water-drinking, who showed triphasic waves on EEG. The patient was a 50-year-old man who had been undergoing medical treatment in a mental hospital since he was suffering from schizophrenia diagnosed at the age of 35. He had sometimes had a tendency to drink a large amount of water since 45 years old. He began to drink water compulsively since three days ago. He vomited just after he drank excessive water with his mouth directly to the tap for several minutes, and soon fell into loss of consciousness. He was transmitted to our hospital because of acute consciousness disturbance on the next day. On neurological examination, he was profoundly comatose with miosis and conjugate deviation to the right side. His extremities showed decorticate posturing. On admission, serum sodium level was 101 mEq/l, and plasma osmolality was 208 mOsm/l. Serum enzymes derived from muscle and myoglobin were markedly elevated. But there was no laboratory evidence of the other metabolic disorders such as hepatic or renal disease. Computed tomography of the brain disclosed severely diffuse swelling with largely obliterated sulci and narrowed ventricles. EEG showed triphasic waves predominantly over centro-parieto-occipital portion, behind which there was slow wave activity with a loss of normal alpha wave activity. Immediately, treatment began by a combination of saline and glyceol infusion for the purpose of correcting severe hyponatremia, subsequently removing brain edema. As serum sodium level gradually returned to normal, the brain CT findings were getting better.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934766 TI - [A case of phenytoin intoxication induced by hypothyroidism]. AB - A 42-year-old woman who presented phenytoin intoxication induced by acute hypothyroidism was reported. She had a 29-year history of hypothyroidism and a 18 year history of epilepsy. She was treated with phenytoin (PHT) 100 mg, mephobarbital (MPB) 200 mg, valproic acid (VPA) 400 mg and thyroid powder 100 mg daily for 2 years. She had no medical problem until she noticed gait disturbance and diplopia which appeared 1 month after sudden withdrawal of thyroid powder. On admission, she was somnolent and somewhat disoriented. She had nystagmus in horizontal direction of gaze. Her speech was slurred and she could not sit nor stand due to trunkal ataxia. There was prominent intentional tremor in finger nose test and heel-shin test showed severe ataxia. Blood cell count and blood chemistry examinations were normal. Serum PHT, phenobarbital (PB) levels were elevated as to 26.4, 36.4 micrograms/ml, respectively. VPA level was low. The endocrinological examinations revealed primary hypothyroidism. EEG showed generalized slow background, but cranial MRI, EMG, SEP and ECG were normal. Thyroxine (T4) administration was started soon, and in the course of thyroid hormone replacement, her cerebellar symptoms gradually improved and serum PHT level decreased even to the subtherapeutical level with the same amount of antiepileptic drugs treatment. By the 40th day of admission, thyroid function became normal and cerebellar signs disappeared, however, she needed 200 mg PHT daily to obtain good control of epilepsy. Cerebellar symptoms of this patient were thought to be PHT intoxication rather than ataxia caused by hypothyroidism itself from the viewpoint of clinical manifestations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934767 TI - [A case of Kearns-Sayre-Shy syndrome with abnormal signal intensity on MRI in cerebral white matter and brainstem]. AB - A 42-year-old woman was admitted for complaining of gait disturbance lasting for 2 years. She had a past history of hearing loss and bilateral ocular ptosis since her age of 21 years. Neurological examinations revealed severe external ophthalmoplegia, ptosis and muscular weakness of neck and extremities, but no dementia. Laboratory examinations showed high level of serum CK and slight elevations of CSF protein, lactate and pyruvate. The QT interval on ECG was prolonged. The EEG finding was slightly abnormal. The neurogenic pattern on EMG was noted. Muscle biopsy was performed at the quadriceps muscle. Its specimens demonstrated mixed changes of muscular atrophy and ragged red fibers. From these findings, Kearns-Sayre-Shy syndrome was diagnosed. It was noted in this case that brain MRI (T2-weighted image) revealed bilateral diffuse high signal intensity areas on cerebral white matter and brainstem. It seems that the lesions of central nervous system may progress subclinically for many years in cases of KSS, as our case shows. PMID- 1934768 TI - [A child case of atypical chronic fasciitis--diagnostic usefulness of muscle CT scan]. AB - Eosinophilic fasciitis is an uncommon disorder characterized by peripheral blood eosinophilia, hypergamma-globulinemia, and inflammation of fascia and skin. Its typical symptom in the acute stage includes muscle pain and swelling, followed by slowly progressive joint contractures. We report an 11-year-old girl with pathological diagnosis of chronic fasciitis, probable eosinophillic fasciitis. Her first symptom was chronic symmetrical joint contractures, which developed when she was 4 years old. She had atypical course as compared with patients described in literature, lack of acute symptom and very early onset of the disease. Her muscle CT scan revealed very fibrotic fascia, which might be responsible for joint contractures. Muscle and fascia biopsies were performed to confirm the diagnosis. The fascia was very fibrotic containing mononuclear cell infiltration, compatible with a chronic stage of eosinophilic fasciitis. In conclusion muscle CT scan is useful for differential diagnosis of this disorder in patients presenting with chronic symmetrical joint contractures, but without acute inflammatory symptom. PMID- 1934769 TI - [A mechanism of cheiro-oral syndrome due to brainstem lesions, a case of a dissecting aneurysm of the basilar artery]. AB - A 42-year-old woman developed an abrupt onset of severe headache, nausea, vomiting, unstable gait and numbness around the right side of her mouth and in her right hand. Neurological examination revealed bilateral pyramidal tract signs and hypesthesia of her right palmar tip and the right side of her mouth. However, pain and temperature sensibility was preserved. Cerebrospinal fluid was clear and colorless. CT scan showed an enhancing mass in the prepontine cistern compressing the pontine base. Vertebral angiography revealed irregular narrowing of bilateral vertebral arteries (string sign) proximal to a fusiform aneurysm on the entire length of the basilar artery. MRI showed double lumina in the wall of the aneurysm. The medial lemniscus conducts the discriminatory tactile and the deep sensory impulses from the extremities. The ventral ascending tract of the trigeminal nerve conducts the discriminatory tactile sensory impulses from the face. These two tracts lie close together in the pontine tegmentum, which is also a watershed area of the paramedian branches and circumferential branches of the basilar artery. We suggest that in this case the dissecting aneurysm caused ischemia of these two tracts in the left pontine tegmentum, presenting right cheiro-oral syndrome. PMID- 1934770 TI - [A case of SSPE that showed watershed infarction like image on MRI initially, and progressed to whole brain atrophy]. AB - We reported a 15-year-old male patient of subacute sclerosing panencephalitis (SSPE), progressed from stage I to stage IV. On his admission, his clinical state was stage I with disturbance of generalized attention, myoclonus of upper limbs and no focal cortical signs. After rapid progression to stage III in a month, his clinical state became fairly stable and gradually advanced to stage IV. We followed him with serial CT and MR images. On imagings we found initial lesion in left parietoocipital lobe and spread in right parietoocipital lobe, anterior lobe and then brain stem, showing low density on plain CT scans and high intensity of T2 weighed MR images. This initial lesion situated in watershed area was hardly distinguishable from watershed infarction. In addition, we found blood flow decrease in vertebral artery system with SPECT and Doppler flowmetry. These findings suggested vascular pathogenesis of SSPE. We showed the imaging processes of SSPE progression from formation of initial lesion to demyelination and gliosis of total brain. PMID- 1934771 TI - [Lyme disease with the triad of neurologic manifestations]. AB - A 40-year-old man developed progressive neurologic manifestations following a tick bite with subsequent localized erythema migrans. These manifestations included bilateral sensory radiculoneuritis (T7-12), rectovesical dysfunction, paraparesis, right facial palsy and nuchal rigidity. Both serum and cerebrospinal fluid titers of IgG antibody against Borrelia burgdorferi were 1:8,192 using indirect immunofluorescence assay. No IgM antibody was detected. With high-dose intravenous penicillin and corticosteroid treatment the neurologic symptoms and signs gradually subsided, with a corresponding decrease in the IgG antibody titers. Among the cases of Lyme disease reported so far in Japan, the present case seems to be typical and serious in terms of the severity of nervous system involvement and the intensity of the antibody response. PMID- 1934772 TI - [Local effect of calcitonin gene-related peptide on human sweat gland function]. AB - The effect of local administration of calcitonin gene-related peptide (CGRP) on sweating activity was evaluated on normal human volunteers. CGRP and methacholine chloride (MCH) was dissolved in 0.1 ml of 0.9% NaCl solution to a specified concentration, and was injected intradermally at the center of a 1.3 cm2 forearm test area. The sweat rate was recorded continuously by capacitance hygrometry in a relatively cool environment (Ta, 23 degrees C). CGRP did not elicit any sweat secretion when administrated by alone, but significantly increased the sweat rate when it was administrated with MCH. The maximum enhancement of MCH-induced sweating by CGRP was observed at a concentration of 10(-5) g/ml of CGRP. There was clear dose-dependent relationship between the dose of CGRP and its enhancement. Recently, CGRP-like immunoreactivity is demonstrated to be present in cholinergic nerve terminals around the human sweat glands. These observations have strongly suggested that CGRP enhances the cholinergic sweating activity. Although the underlying mechanism is still obscure, CGRP may enhance the sweating as a consequence of vasodilation which has been known to be a major activity of CGRP. As for the evaluation of human sweat gland function, CGRP-induced peptidergic regulation should be considered as well as cholinergic regulation. PMID- 1934773 TI - [Cerebral blood flow pattern in progressive supranuclear palsy]. AB - It is known that progressive supranuclear palsy (PSP) shows subcortical dementia. The diagnosis of PSP is sometimes difficult because this disorder mimics the clinical features of parkinsonian syndrome. Several PET studies demonstrated frontal hypo-metabolism in PSP patients. We studied the cerebral blood flow (CBF) pattern by single-photon-emission-computed tomography (SPECT) using 123I isopropyl-iodoamphetamine (IMP) in 5 patients of PSP including one autopsy case. Five PSP patients were 3 men and 2 women, mean age of 67.6 years old. Control groups were 3 normal controls (Normal), 7 patients of Parkinson's disease (PD), 5 patients of olive-pontocerebellar atrophy (OPCA), and 4 patients of dementia of Alzheimer's type (DAT). CBF was measured by 123I-IMP SPECT using 400 AC/T Starcam (GE). CBF was measured by semi-quantitative methods. Regions of Interest (ROI's) were located at cerebellar, basal ganglion, and lateral ventricle levels. Each count of ROI was divided by the count of occipital ROI. In all PSP patients, the ratio of relative blood flow to occipital lobe in the frontal and fronto-temporal regions were most markedly affected, showing average reduction rates of 66.6% and 65.5%. These rates showed statistically significant differences to other control degenerative neurological diseases. Our these results correspond to the former PET studies. Moreover, frontal hypoperfusion progressed with advancing clinical stage. The results indicate that CBF study with SPECT is useful to confirm the diagnosis of PSP. It is necessary to clarify the role of the damage in basal ganglia for frontal hypometabolic pattern. PMID- 1934774 TI - [Topographic correlation between basilar artery occlusion and cerebellar involvement--a clinicopathological study]. AB - Nineteen patients (15 men, 4 women) with occlusion of the vertebrobasilar artery were studied in order to identify possible pathomechanism and to define the site of arterial occlusion and the topography of ischemic lesion of the cerebellum. Their mean age at onset was 66.7 years and the final clinicopathological diagnosis were thrombosis of the basilar artery (BA) in 15 patients and embolism in 4. The occlusion of the BA was contiguous to that of the vertebral artery in ten patients. Of these, the occlusion was localized to the caudal portion of the BA in two, to the middle portion in six, and extended to the rostral portion in two. In eight patients, the arterial occlusion was restricted to the BA. Occlusions of the middle portion were observed in four and that of rostral portion in two; in the other two patients, the whole BA was occluded. In one patient, there was no occlusion in the vertebro-basilar artery at the postmortem examination, but infarctions of the base of pons, bilateral cerebellar hemispheres and occipital lobes were confirmed, suggesting recanalization of the occluded BA. Cerebellar lesions were observed in all nineteen patients. Involvements of the area supplied by the superior cerebellar artery (SCA) were found in seventeen, while that of the posterior inferior cerebellar artery (PICA) only in ten. Eight patients had cerebellar lesions supplied by both SCA and PICA. These facts suggest that cerebellar lesions are rather frequent and the SCA areas are more involved than those of the PICA in fatal patients with occlusion of the BA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934775 TI - [Clinical aspects of silent cerebral infarction--MRI findings and its distribution]. AB - High-field MR scans have often showed patchy incidental findings especially in the elderly. We examined 91 patients, without episodes of cerebrovascular disorders previously, who had silent cerebral lesions noted by the 1.5 tesla superconductive system T2 weighted magnetic resonance imaging. They were divided into three subtypes by the localization of foci. The 23 subjects (25%) showed confined lesions to thalamus and/or internal capsule and/or basal ganglia (the basal ganglia type). The 39 subjects (43%) had lesions predominantly in cerebral cortex and/or subcortical white matter and/or cerebellum (the diffuse subcortical type). Finally, the 29 subjects (32%) had both features of above-mentioned two groups (the mixed type). These subtypes were correlated with age, sex and some of the other risk factors, such as systolic blood pressure, diastolic blood pressure, serum total cholesterol and uric acid, for stroke. The mean age of the basal ganglia type was significantly younger than that of the diffuse subcortical type (p less than 0.001) and than that of the mixed type (p less than 0.001). The diffuse subcortical type consisted of 11 men and 28 women. In the mixed type, it was composed of 21 men and 8 women. These two subtypes had the significant sex differences (the diffuse subcortical type, p less than 0.05 and the mixed type, p less than 0.025). Systolic and diastolic pressures of the basal ganglia type were lower than those of the diffuse subcortical type (systolic, p less than 0.001 and diastolic, p less than 0.025) and than those of the mixed type (systolic, p less than 0.001 and diastolic, p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934776 TI - [MRI in Parkinson's disease and vascular parkinsonism--study on the lesion of substantia nigra]. AB - We examined the magnetic resonance (MR) image of midbrain and striatum in 30 patients with Parkinson's disease (PD), 10 patients with vascular parkinsonism (VP) and 10 age-matched control subjects. Studies were performed on a high field strength (1.5 tesla) MRI unit. T2 weighted spin echo pulse sequence (TR2500ms/TE40ms) was used. We measured the width of the pars compacta signal in patients and controls on the basis of the method described by Duguid et al. Intensity profiles of a straight line perpendicular to the pars compacta through the center of the red nucleus were made on an image of the midbrain. We measured the width of the valley at half-height between the peaks of intensity representing the red nucleus and the crus cerebri-pars reticulata complex and used this as an index of the width of the pars compacta signal. The results were as follows: 1. The mean width of the pars compacta signal was 2.7 mm (SD = 0.3) in the PD group and 4.3 mm (SD = 0.6) in controls. The difference between the means was highly significant (p less than 0.01). While not significant statistically, there was a trend toward narrowing of the width of pars compacta signal of substantia nigra in the PD group as the Yahr's grade or disease duration progressed. In hemiparkinsonism, MRI revealed significant narrowing of the pars compacta signal on the contra-lateral side to the clinical predominant side compared with the ipsi-lateral side. 2. The mean width of the pars compacta signal was 3.9 mm (SD = 0.4) in the VP group, but the decrease was not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934778 TI - [Marchiafava-Bignami disease with symptoms of the motor impersistence and unilateral hemispatial neglect]. AB - Machiafava-Bignami disease (MBD) occurs in the alcoholic patients. It is characterized clinically by interhemispheric disconnection syndrome, resulting from demyelination and necrosis of the corpus callosum. We performed a neuropsychological study of an alcoholic patient, diagnosed as MBD by X-ray computed tomography (CT) and magnetic resonance imaging (MRI). 123I IMP-SPECT of the patient revealed the reduction of the blood flow in both cerebral hemispheres without laterality though both the X-ray CT and MRI showed no abnormality in the cerebral hemispheres. In neuropsychological studies, we observed not only interhemispheric disconnection syndrome such as an unilateral left agraphia and left apraxia but also left hemispatial neglect demonstrated in right-hand performance and motor impersistence. Because there were no abnormal lesions in the right hemisphere, these symptoms might be attributable to the lesions of corpus callosum. PMID- 1934777 TI - [Chronic dementia in Parkinson disease treated by long-term administration of anticholinergic drug--evaluation of neuropsychological test, PET, and SPECT]. AB - It is known that the anticholinergic drug causes acute psychosis and memory disturbance, which may be due to cholinergic dysfunction. But it has not been well described that the anticholinergic drug causes chronic dementia after long administration. We describe six cases of chronic dementia, which is thought to be induced by anticholinergic drug. We conducted detailed neuropsychological and neuroradiological examination in these six cases. All of them were Parkinson's disease, and had used anticholinergic drug for more than six months without any side effect, and then their initial symptom of dementia appeared, followed by chronic dementia. All cases recovered reversibly from dementia within a few weeks after stoppage of taking anticholinergic drug. And any of our cases had no possibility in the cause of chronic dementia other than the side effect of anticholinergic drug. Detailed neuropsychological examinations (WAIS, WMSR, and so on) were conducted in all cases, SPECT was in two cases, and PET was in one case, before and after stoppage of the anticholinergic drug. And in all cases, brain MRI was conducted. The indices of attention, verbal memory, visual memory, and delayed recall were significantly elevated after stoppage of drug. And both verbal IQ and performance IQ were increased after stoppage of drug, too. SPECT and PET revealed significant improvement, which showed diffuse and generalized change, not localized change. PMID- 1934779 TI - [A case of midbrain and thalamic infarction showing Collier's sign in one side and blepharoptosis in the other side]. AB - A 68-year-old man was admitted to the hospital complaining of aphasia and right hemiparesis. Neurological examination revealed aphasia, right hemiparesis and ataxia in the left upper extremity. He showed striking ocular symptoms: intense retraction of the right eyelid (Collier's sign), complete ptosis of the left eyelid which might conceal Collier's sign, marked upward gaze palsy and slight downward gaze palsy. Vertebral angiography and MRI revealed an infarction in the left medial area and the left crus cerebri in the upper midbrain, the left subthalamic area inferomedially extending from the adjacent area to the posterior commissure and the medial area in the left thalamus resulting from occlusion of the left mesencephalic artery. From these MRI findings and the reports on pathological findings of patients with Collier's sign, we suggest that damage in the posterior commissure or its adjacent area may be responsible for the sign. Upward gaze palsy is often associated with Collier's sign because fibers mediating upward gaze may decussate in the posterior commissure. Third nerve palsy is also associated with the Collier's sign in some patients. The mechanism creating Collier's sign may be a disturbance of inhibitory fibers leading to the motoneuron pool of the levator muscle in the posterior commissure or its adjacent area. PMID- 1934780 TI - [Electrophysiological studies of a case of startle disease]. AB - A 53-year-old female with startle disease (major form) was reported. An abnormal startle response was the most prominent clinical feature. Physical examination revealed left lateral gaze palsy and left extensor plantar response. The caloric test evoked no responses bilaterally. Blood examinations including lysozomal enzymes and radiological examinations including MRI of the brain were all normal. A pathological startle reflex was elicited by the tap on the upper lip, causing the marked extension of the head with the elbow, hip, and knee joints slightly flexing. The earliest reflex activity in a surface-EMG study was recorded in the masseter muscle and the reflex then spread down the brain stem and the spinal cord. The duration of the discharge varied from 16 to 30 ms. The onset latencies of these responses from the tap were 11.2 ms, 12.7 ms, 14.5 ms, 25.7 ms, 38.5 ms, and 47.5 ms in the masseter, sternocleidomastoid, posterior-neck, biceps brachii, quadriceps femoris, and tibialis anterior muscle, respectively. An averaged electroencephalogram triggered by the taps showed no abnormal EEG activity preceding the pathological startle response, although a negative peak, which was thought as a normal early component of the trigeminal somatosensory evoked potentials, was followed by the reflex. High amplitude SEPs and long loop reflexes were observed following stimulation of the posterior tibial nerve but not of the median nerve. Blink reflexes and auditory evoked potentials were normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934781 TI - [HTLV-I associated myelopathy with Hashimoto's thyroiditis--a report of two cases]. AB - We reported two cases of HTLV-I associated myelopathy with Hashimoto's thyroiditis. Case 1 is a 47-year-old female, who has had Hashimoto's thyroiditis since the age of 29. At the age of 38, she first noticed difficulty in walking which progressed gradually. At the time of examination, she showed a spastic gait, increased deep tendon reflexes in four extremities, hypesthesia of the feet, mild bowel and bladder disturbances. Anti-HTLV-I antibody was increased to the titer of 16,834 in the serum and of 32 in the cerebrospinal fluid by PA method. Hypothyroidism was present and the titers of microsome test and thyroid test were elevated to 102,400. Anti-T4, and anti-T3, and anti-thyroglobulin antibodies were found. Ultrasonography of the thyroid revealed its enlargement and decreased echo signals. Thyroid scintigram showed inhomogeneous 123I uptake and some defective areas of the uptake. Histological examination of the biopsy specimen of the thyroid demonstrated marked lymphocytic infiltration, germinal centers, hypertrophy of follicular epithelium, and interstitial fibrosis, which were consistent with Hashimoto's thyroiditis. Case 2 is a 60-year-old female who has had slowly progressive gait disturbance since her childhood. She became unable to walk at the age of 35. At the time of examination, she had a spastic gait, increased deep tendon reflexes bilaterally, and positive Babinski signs. Anti-HTLV-I antibodies were increased to a titer of 8,192 in the serum and of 32 in the cerebrospinal fluid. Thyroid function was normal. However, anti-thyroid antibodies were positive and histology of the thyroid showed lymphocytic thyroiditis, which were consistent with mild grade of Hashimoto's thyroiditis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934782 TI - [A case of spinal arteriovenous malformation associated with syringomyelia extended over the entire spinal cord that presented mainly as spastic paraparesis]. AB - A 48-year-old housewife was hospitalized because of spastic paraparesis accompanied by dysesthesia and amyotrophy in her lower extremities, and by urinary disturbances. At the age of 35 years she noticed tingling sensations in her right foot and gradually her gait became spastic. In a few years lumbago and the spinal form of intermittent claudication developed. When she was 41 years old muscle wasting was noticed in her right leg, and in four years the same feature was also seen in her lower left limb. Plain X-ray films showed a wide cervical canal with no signs of basilar impression. On MRI we could see a polycyst-like syrinx that extended over the entire spinal cord. In addition the surfaces of the lower thoracic cord seemed irregular, but arteriovenous malformation itself was not visualized. Neither hydrocephalus nor Chiari malformation was accompanied. Needle EMG examination revealed some neurogenic changes in the muscles of both lower limbs. Cystometry proved uninhibited contractions of the detrusor muscle and the existence of detrusor-sphincter dyssynergia. Myelography showed an enlarged spinal cord above the D11-12 level with a shadow of worm-like appearance between the D7-12 level. CSF protein was elevated. Spinal angiography confirmed the presence of single coiled vessels with a nidus at D8-10 that were fed by bilateral D10 intercostal arteries and drained to D7, D9 or D12. Embolization of these abnormal vessels was conducted, and since then the patient's condition has remained stable. Vascular malformation is a rare cause of secondary syringomyelia. Clinical manifestations are determined mainly by the level of vascular malformation and are not reflective of the level of syrinx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934783 TI - [A case of acute cerebellar encephalitis due to Cryptococcus neoformans]. AB - A case of acute cryptococcal cerebellar encephalitis with CT enhancement confined to the cerebellum is reported. A 46-year-old man with hepatoma was admitted with chief complaints of headache, fever and dizziness. On admission, cerebellar signs (disturbance of finger-to-nose test and of heel-to-knee test, intention tremor, and truncal ataxia) were neurologically noted. However, there were no brainstem signs. Head CT showed swelling and enhancement of the cerebellar cortex and dilatation of the cerebral ventriculi. Cryptococcus neoformans was detected in a culture of the patient's CSF. Clinical symptoms and signs, and enhancement of the cerebellum on CT gradually diminished after administration of anti-fungal drugs, and CSF became negative for cryptococcal antigen 6 months after admission. PMID- 1934784 TI - [Post-hemiplegic dystonia with a discrete lesion in the postero-lateral part of the contralateral putamen]. AB - We report a 56-year-old man with so-called post-hemiplegic dystonia in the right lower extremity. His cranial CT scans and MRI revealed a small discrete lesion in the postero-lateral part of the contra-lateral putamen. The location of his putaminal lesion did not seem to correspond exactly to the leg area according to the topographical mapping of the monkey putamen. The mechanism of his focal dystonia is discussed including the possibility of the development of dopaminergic hyperactivity in the remaining area of the putamen as an account for his dystonic movement. PMID- 1934785 TI - [A case of herpes simplex encephalitis with periodic lateralized epileptiform discharges]. AB - A case of a 50-year-old male with herpes simplex encephalitis was reported. An EEG examination revealed periodic lateralized epileptiform discharges (PLEDs) on the right hemisphere on April 17, 1990. Another EEG performed on April 26 showed PLEDs on the left hemisphere, dominantly on the temporal lobe. On and after May 2, PLEDs have not been detected. SPECT showed hyperperfusion in the right temporal and occipital lobe son April 26. T1 weighted MRI examined on April 18 showed low signal intensity and T2 and proton weighted imagings revealed high signal intensity in the greater part of the right temporal lobe and a similar abnormality in a part of the left temporal lobe. Although the origin of PLEDs is still controversial, these findings suggest that, at least in the case of herpes simplex encephalitis, PLEDs appear in the early progressive stage of the inflammatory lesion. PMID- 1934786 TI - [A case of distal lower motor neuron syndrome associated with IgM anti-GM1 antibodies]. AB - A 34-year-old man had noted progressive weakness in his right hand. On admission at age 39, cranial nerves were not involved. Fasciculations were observed in his upper limb girdles. Neurological examination revealed severe wasting and weakness of arms and the right hand, whereas mild in the left hand. The deep tendon reflexes were absent in the upper extremities, but normal in the lower extremities. No sensory disturbances were observed. Motor and sensory nerve conduction velocities were normal, and multifocal conduction block was not observed. EMG showed neuropathic changes in all 4 limbs and sternocleidomastoideus muscles. Serum immunoelectrophoresis failed to detect an M protein. High-performance thin-layer chromatography with immunostaining revealed that his serum IgM reacted with GM1, but not reacted with GM2, GD1a, GD1b, and asialo-GM1. PMID- 1934787 TI - [A case of cerebrotendinous xanthomatosis with spastic paraparesis, epilepsy, and bradykinesia]. AB - A 26-year-old female developed mental deterioration, general convulsion, cataract and spastic gait in order since her entrance into elementary school. A diagnosis of cerebrotendinous xanthomatosis (CTX) was made because of hypercholestanolemia. At the time of admission, cataract, a mild thickening of Achilles tendons, mental deterioration, spastic paraparesis, truncal ataxia, and bradykinesia were noted. Bilateral slowing of 2 to 7 Hz was recorded in EEG, and brain CT and MRI revealed mild cerebellar atrophy. HVA and 5-HIAA levels in CSF were low. Oral administration of chenodeoxycholic acid, 300 mg per day, resulted in improvement of bradykinesia and EEG abnormality, increase of HVA and 5-HIAA levels in CSF, and decrease of serum cholesterol level in two weeks. Bradykinesia observed in the present case is a rare clinical finding of CTX, and the improvement of bradykinesia soon after the treatment with chenodeoxycholic acid has not been reported yet. This case is important for elucidating the mechanism of neurological disorders in CTX. PMID- 1934788 TI - [Oculomotor nucleus syndrome: crossed innervation of the superior rectus muscle]. PMID- 1934789 TI - Diagnostic significance of apparent abnormal bowel activity on Ga-67 scans in AIDS patients. AB - Twenty-one Ga-67 studies on 19 AIDS patients were analyzed to investigate the relationship between clinically acute gastrointestinal disease and abnormal scintigraphic bowel activity. Whole body images were obtained at times ranging from 4 to 192 hours, with most exams imaged at 48 and 72 hours. Abnormal bowel activity was observed in eight of 21 exams. Patients experienced acute GI disease during seven studies. Gallium scan results and clinical presentation agreed in 14 cases; both were abnormal in four and normal in 10. However, four exams showed abnormal activity in asymptomatic patients, while three normal studies were obtained in patients with clinically evident GI disease. Sensitivity was 57% and specificity 71%. Positive predictive value was .50 and negative predictive value .77. All true-positive cases were associated with Mycobacterium avium intracellulare (MAI) infection. This study implies that gallium imaging is unreliable for diagnosing acute bowel disease in AIDS patients, but may suggest a particular pathogen (MAI) in the symptomatic individual. PMID- 1934790 TI - Reverse oblique reconstruction for SPECT of the spine. AB - Anatomic localization of spine lesions, shown by Tc-99m phosphonate SPECT, to facet joint or pedicle is often difficult due to limitations in resolution. Indirect localization, relating lesion position on sagittal reconstruction to the adjacent visible vertebral bodies and also to patient spine radiographs, might be required. Some laterally placed lesions, however, cannot be visualized in the more midline slices showing the vertebral bodies. Oblique tomographic reconstruction overcomes this limitation. PMID- 1934791 TI - A technique for intraoperative bone scintigraphy. A report of 17 cases. AB - Since 1981, intraoperative bone scanning has been used at Stanford University Hospital to assist in the localization and excision of skeletal lesions in the surgical suite. The utility of bone scans to detect lesions not otherwise "visible" is valuable in guiding the surgeon to the pathological site. In addition, intraoperative scanning can define the exact amount of tissue to be excised, averting excessive surgery near joints or along weight-bearing bones. Seventeen cases are presented. PMID- 1934792 TI - Diagnosing osteomyelitis in Gaucher's disease. Observations on two cases. AB - Bone scans in two patients with Gaucher's disease were reported as consistent with Gaucher's-associated osseous crises. A bone-radiogallium subtraction study was also initially negative in each individual (although it later became positive in one). At surgery both patients were seen to have osteomyelitis. These two cases point out the difficulty in attempting to diagnose osteomyelitis in the presence of Gaucher's bone disease. A possible role for MRI in such instances was mentioned. Also noted was clinical reluctance to accept a diagnosis of osteomyelitis (positive bone-radiogallium subtraction study) in an afebrile Gaucher's patient. PMID- 1934794 TI - Tc-99m HMPAO labeled donor leukocyte scan in liver transplant. AB - Tc-99m HMPAO labeled donor leukocytes were used to image the focus of an hepatic infection in a 32-year-old liver transplant patient. Six hours after the administration of labeled leukocytes, radioactivity accumulation was detected in the liver suggesting an intrahepatic infection focus. Diagnosis of infection was confirmed at surgery. PMID- 1934793 TI - Duodenal hematoma. A mechanical cause for enterogastric reflux in cholescintigraphy. AB - Enterogastric reflux occurs in normal and abnormal conditions. When pronounced, it is a nonspecific indicator of pathology. There are relatively few published reports discussing enterogastric reflux as a prominent finding on cholescintigraphy. A unique case of pronounced enterogastric reflux from an obstructing duodenal hematoma is presented. PMID- 1934795 TI - Renal trapping of In-111 troponolate labeled platelets in thrombotic thrombocytopenic purpura. AB - A patient with active thrombotic thrombocytopenic purpura underwent examination with In-111 troponolate labeled autologous platelets. A mean platelet survival of 1.2 days was found, comparable to formerly described studies using other methods. Furthermore, remarkable renal uptake of radioactivity consistent with abnormal platelet trapping was demonstrated. In the absence of any other signs of renal involvement, the conclusion was reached that the platelet scan is a sensitive and direct method for showing renal involvement in thrombotic thrombocytopenic purpura. PMID- 1934796 TI - Pheochromocytoma associated with prior carotid body tumors (chemodectomas). Detection with I-131 MIBG. AB - Chemodectomas (carotid body tumors) were surgically removed on two occasions, first 10 years and then 3 months prior to detection with I-131 MIBG of an adrenal pheochromocytoma in a 32-year-old man with a family history of chemodectoma. Recent reports suggest patients with multiple and/or familial instances of chemodectoma frequently have associated catecholamine-secreting tumors detectable with I-131 or I-123 MIBG. This case documents the above association and suggests that any patient with proven carotid body tumor(s) be screened for catecholamine secreting tumors via urinary/plasma catecholamine determinations. PMID- 1934797 TI - Right ventricle wall motion abnormalities in patients treated with chemotherapy. AB - Doxorubicin is a cytotoxic agent used in the treatment of patients with various malignancies. Its clinical value is limited by a dose-related cardiotoxicity. Wall motion was analyzed in 52 patients during different stages of treatment. Eleven patients were studied once, and in 41 patients serial radionuclide ventriculography was performed from 2 to 5 times. Abnormal wall motion was found in 96 out of 1,062 segments (9.0%), of which 33 out of 735 (4.5%) were in the left ventricle (LV) and 65 out of 327 (19.9%) were in the right ventricle (RV). The number of abnormalities in the RV was significantly higher than in the LV (P less than 0.001). Regional analysis of LV and RV in 109 40 degrees LAO studies and in 102 75 degrees LAO studies showed abnormal wall motion in the following segments: LV--posterobasal 6 (5.9%), inferior 2 (2.0%), anterior 5 (4.9%), anteroseptal 11 (10.1%), apical 5 (4.6%), posterolateral 4 (3.7%); RV--septal 44 (40.4%), apex 15 (13.8%), and the free wall 6 (5.5%). The left ventricular ejection fraction decreased from 74% median (M) in baseline studies to 54% (M) in the highest dose group (greater than 650 mg/m2). The present data show an increased number of wall motion abnormalities in the RV compared with the LV, particularly in the RV septum (P less than 0.001). PMID- 1934798 TI - Visualization of a recanalized umbilical vein on hepatobiliary imaging with CT correlation. PMID- 1934799 TI - Detection of clinically occult axillary metastases from breast cancer during stress TI-201 scintigraphy. PMID- 1934800 TI - Alterations of the dynamics in the arterial mesenteric circulation secondary to atherosclerosis. A new pitfall of GI bleeding studies with Tc-99m tagged RBCs. PMID- 1934801 TI - Serendipitous diagnosis of hyperthyroidism with Tc-99m bone scan. PMID- 1934802 TI - Diffuse jaw uptake. An unusual finding in neurofibromatosis. PMID- 1934803 TI - Intra-abdominal retained surgical sponges presenting as a photopenic mass on scintigraphy. PMID- 1934804 TI - Absent or faint renal uptake on bone scan. Etiology and significance in metastatic bone disease. AB - A review of 14,296 unselected bone scans identified 889 scans showing absent or faint renal uptake. The majority of cases were associated with renal insufficiency (816/889; 91.8%), while widespread metastatic bone disease was the most common cause in a group of patients without renal disease (53/889; 6.0%). Of the 140 patients with prostate cancer, 108 (77.1%) had evidence of bone metastasis, 19 of whom (17.6%) revealed absent or faint renal uptake, demonstrating that poor renal uptake is more frequently associated with prostate cancer than with any other malignancy. Of note was that 162 out of 328 (49.4%) patients with stomach cancer at varying stages showed evidence of bone metastasis, and 14 of them (8.6%) showed poor renal images on bone scan. Interestingly, ankylosing spondylitis and rheumatoid arthritis were occasional causes of lack of renal activity (4 and 3 cases, respectively). A case of adult form osteopetrosis, showing strikingly increased uptake mainly in the long bones with markedly diminished renal uptake, was also included in this study. Of the 53 bone scans with metastatic disease showing poor renal uptake, 44 (83.0%) revealed evidence of diffuse or multiple metastases in both spine and ribs, while 49 (92.5%) showed malignant involvement in three or more regions and 35 (66.0%) in four or more regions, suggesting widespread bone involvement in most cases. PMID- 1934805 TI - Concentration of Tc-99m MDP in ovarian carcinoma and its soft tissue metastases. AB - A patient with ovarian carcinoma was evaluated for skeletal metastasis with a routine whole body bone scan. Although no bone metastases were visualized, there was dramatic accumulation of tracer in the soft tissues of the abdomen. CT revealed calcifying soft tissue metastases on the liver surface, the bowel serosa, and in the pelvis corresponding to the abnormal areas of Tc-99m MDP uptake. Tumor necrosis and ongoing calcification within the metastatic sites are possible explanations for this unusual soft tissue concentration of the bone seeking radiopharmaceutical. In patients with metastatic ovarian carcinoma, careful review of extraosseous regions on bone scan images may provide valuable diagnostic information. PMID- 1934806 TI - The 'cold hip' sign on bone scan. A retrospective review. AB - The "cold hip" sign on bone scan is often seen in patients referred with irritable hip. This sign is due to fluid in the hip joint under pressure causing impaired perfusion of the structures within the joint capsule. In a retrospective review, 22% of patients with this sign on bone scan were found to have septic arthritis at surgery. This fact would appear to justify surgical drainage or aspiration of any hip showing this sign on scan. An attempted follow-up study through the medical records was incomplete because of the short follow-up on most patients. The possibility that temporary impairment of blood supply to the head of the femur causes long-term damage to the hip is unanswered on this study, and a long-term recall follow-up study is underway. PMID- 1934807 TI - Cerebral perfusion abnormalities in therapy-resistant epilepsy in mentally retarded pediatric patients. Comparison between EEG, X-ray CT, and Tc-99m HMPAO. AB - Thirteen mentally retarded pediatric patients aged 4 to 13 years with therapy resistant epilepsy underwent Tc-99m HMPAO brain perfusion SPECT studies. The results (abnormal in 12 of the 13 patients) were compared with EEG results in 12 of the 13 patients (abnormal in all 12) and x-ray CT in 11 of the 13 patients (normal in 9). Patients with spikes on EEG had foci of increased uptake on HMPAO. This study confirms that HMPAO is sensitive in detecting perfusion abnormalities and localizing epileptic foci in this group of patients. PMID- 1934808 TI - Clinical SPRINT imaging. Preliminary results compared to conventional SPECT brain scanning using Tc-99m HMPAO. AB - We have performed initial clinical studies using the high resolution single photon ring tomograph (SPRINT) and Tc-99m HMPAO. To determine what additional anatomic detail can be depicted using this high resolution, dedicated head, multidetector SPECT device compared to conventional SPECT, six patients with stroke and one normal volunteer were imaged after the injection of 20 mCi Tc-99m HMPAO on a conventional rotating Anger gamma camera (GE-400AC), followed immediately by imaging on SPRINT. Imaging acquisition on the GE-400AC gamma camera was performed using 360 degrees rotation, 64 stops, at 30 sec/stop, yielding an average of 985,714 counts for a 10.0 mm thick slice. GE-400AC images were of good quality, having in-plane full width half maximum (FWHM) resolution of approximately 15 mm. SPRINT acquisition of image data was performed using both the high resolution and high sensitivity apertures, with data collection over 15 or 20 minutes of imaging time accumulating approximately 500,000 counts and 1,000,000 counts, respectively, from patients in a 10.0 mm thick slice, achieving an in-plane FWHM resolution of approximately 8 mm and 10 mm for the two apertures, respectively. Both image resolution and contrast for visualization of gray, white, and cerebral spinal fluid filled brain structures were improved using SPRINT compared with the GE-400AC. We conclude that SPRINT is well suited for brain imaging with Tc-99m HMPAO and is of particular value for applications demanding high resolution. PMID- 1934809 TI - Increased brain retention of Tc-99m HMPAO following acetazolamide administration. AB - Sixty-five patients referred for Tc-99m HMPAO SPECT brain perfusion studies had measurements of global Tc-99m HMPAO retention after injection at rest and after acetazolamide pretreatment. Acetazolamide produced relative changes in Tc-99m HMPAO retention similar to those previously reported with Xe-133 regional cerebral blood flow (rCBF) measurements. This addition to imaging protocols allows another objective evaluation of the cerebral vascular reserve. PMID- 1934810 TI - SPECT evaluation of brain perfusion reserve by the acetazolamide test using Tc 99m HMPAO. AB - This report describes a new approach to the evaluation of brain perfusion reserve using Tc-99m HMPAO SPECT. Consecutive brain Tc-99m HMPAO SPECT studies before and after acetazolamide (Diamox) administration were performed within 30 minutes on 19 patients with significant vascular occlusive lesions. Thirteen patients showed decreased perfusion reserve and four patients maintained perfusion reserve in the affected vascular territories after Diamox administration, providing additional information to baseline Tc-99m HMPAO SPECT in 17 (89%) patients. Although flow augmentation post-Diamox was underestimated, possibly due to the nonproportionality of Tc-99m HMPAO activity to true blood flow, significant changes in the brain perfusion pattern were both visually and quantitatively determined using an image subtraction technique. This consecutive Tc-99m HMPAO SPECT technique seems to be of practical use for the evaluation of brain perfusion reserve and for the improvement of the sensitivity of detecting pathologic areas. PMID- 1934811 TI - Embolic stroke following carotid radiation angiopathy demonstrated with I-123 IMP brain SPECT. AB - Radiation angiopathy was developed by the process of accelerated atherosclerosis at the site of irradiation. The case of a 44-year-old man with right hemiparesis showing a high signal intensity in the left semioval center on MRI and a defect in the left temporo-parietal area with subsequent filling-in with I-123 IMP brain SPECT is reported. Digital subtraction angiography showed typical radiation angiopathy with ulceration in the left common carotid artery. Twenty-four years previously, he underwent curative irradiation of a neck mass that revealed Hodgkin's disease by biopsy. The emboli formed at the site of radiation-induced angiopathy and caused cerebral infarction. The perfusion abnormality in the territory of the embolic artery was detected by I-123 IMP SPECT. Long-term survivors of neck irradiation are at high risk for the development of carotid arterial disease and should be watched carefully. PMID- 1934813 TI - Bone imaging in unusually massive breast carcinoma with chest wall invasion. PMID- 1934812 TI - Anti-platelet monoclonal antibody P256 in the diagnosis of renal transplant rejection. AB - Platelets labeled in vitro with In-111 have a recognized place in the diagnosis of renal transplant rejection. Following their introduction for imaging thrombi, radio-labeled anti-platelet antibodies may also have a role in the diagnosis of transplant rejection. Four of 11 patients with recently donated transplants had biopsy-proven acute rejection episodes close to the time of administration of In 111 P256 Fab' fragment, which recognizes the IIb-IIIa fibrinogen receptor on primate platelets. The transplant-to-background count rate at 3 and 24 hours after these injections were 2.2 (SE 0.14) and 2.3 (0.23), respectively, almost identical to the ratios, 2.0 (0.1) and 2.2 (0.11), recorded at the corresponding times after 19 injections of P256 Fab' that were remote in timing from rejection episodes. P256 Fab' may have value in the detection of postoperative venous thrombosis, but it has no value for the detection of transplant rejection. PMID- 1934814 TI - Extracardiac activity with Tl-201 in a pleural mesothelioma recurrence. PMID- 1934815 TI - Totem pole sign. Bone densitometry study with retained barium. PMID- 1934816 TI - A false-positive artifact in the investigation of osteitis pubis. PMID- 1934817 TI - Cholescintigraphic demonstration of biliary fistula and of normalization after choledochoduodenostomy and correction of common bile duct obstruction. PMID- 1934818 TI - Scintigraphic findings in transplanted crossed fused renal ectopia. PMID- 1934819 TI - Pseudobullseye sign of the testicle. A window to the peritoneum. PMID- 1934820 TI - Potential pitfall in bone scanning by transcutaneous nitroglycerin. PMID- 1934821 TI - Cholescintigraphy in the diagnosis of intrahepatic cholestasis. How specific is it? AB - Previous results from tests on a limited number of patients suggested that the combination of relatively normal hepatocyte clearance, prolonged parenchymal transit time, and eventual passage of radiotracer into the intestine or gallbladder without evidence of biliary tract dilatation were relatively specific for intrahepatic cholestasis. We reevaluated the specificity of cholescintigraphy for the diagnosis of intrahepatic cholestasis in an unselected group of patients from a general hospital. Sixteen patients had the cholescintigraphic findings of intrahepatic cholestasis and an established diagnosis of biliary tract dilatation or nondilatation by ultrasound, ERCP, or intraoperative cholangiography. Using 6 mm as the upper limits of normal for the diameter of the common hepatic duct by ultrasonography resulted in a specificity of 63% (10 correct out of 16); using 6 mm plus 1 mm for for every decade over 60 years of age gave a specificity of 75% (12 correct out of 16); and using the more liberal criterion of 8 mm as the upper limits of normal increased the specificity to 81% (13 out of 16). The data suggest that cholescintigraphy alone is unreliable in differentiating intrahepatic cholestasis from extrahepatic obstruction, even when the obstruction is partial and radiotracer eventually passes through the extrahepatic biliary tract. PMID- 1934822 TI - The cystic duct sign during morphine-augmented cholescintigraphy. AB - Visualization of a "dilated cystic duct" during standard hepatobiliary imaging represents a potential source of false-negative cholescintigraphy. Intravenous morphine, commonly used to shorten study time and improve the specificity of hepatobiliary imaging, may, by virtue of its pharmacologic/physiologic actions, accentuate the appearance of a "dilated cystic duct." We present a case of transient cystic duct visualization following morphine administration in a patient with an obstructing cystic duct calculus. PMID- 1934823 TI - False-positive hepatic blood pool scintigraphy in metastatic colon carcinoma. AB - A rare false-positive red blood cell scintigram occurred in a 49-year-old woman with two metastases from a primary adenocarcinoma of the sigmoid colon. Although the blood flow and static planar images were unremarkable, a 1-hour postinjection SPECT study showed a focus of increased activity in the inferior right lobe and a second photopenic focus in the dome. Following a trisegmentectomy, pathologic examination revealed the two metastases with no evidence of a hepatic hemangioma. Microscopy, however, showed a discrete area of nonspecific reactive changes (focal sinusoidal dilation and congestion) immediately adjacent to teh metastasis in the inferior right lobe. It is postulated that the SPECT focus of increased activity occurred secondary to the labeled blood pool within the area of sinusoidal dilation, rather than within the adjacent metastasis. PMID- 1934824 TI - 'Cold lesions' on bone scan. A case of metastatic squamous cell carcinoma of the penis. AB - Photopenic osseous lesions are a well-recognized but unusual manifestation of metastatic disease on bone scintigraphy. Common primary tumors giving rise to such lesions include lung, breast, renal, and thyroid. This case report illustrates multiple "cold" osseous metastases from aggressive penile squamous cell carcinoma without radiographic destruction. PMID- 1934825 TI - Radionuclide imaging of soft tissue masses with Tc-99m DTPA. AB - A scintigraphic study was carried out on 48 patients presenting with palpable soft tissue masses. Imaging was carried out using Tc-99m DTPA in three phases (dynamic, blood pool after 5 minutes, followed by late scans after 2 hours). The resultant uptake of the agent was categorized as consistently positive (14 cases), initially positive but progressively negative (7 cases), initially negative but progressively positive (7 cases), and consistently negative (20 cases). Histopathologic examinations were carried out for all cases following biopsy. A variety of malignant and benign masses were found to localize DTPA, whereas all masses that did not concentrate the agent were proven to be lipomas. In order to determine whether the uptake of DTPA bore any relationship to blood flow, additional studies using Tc-99m labeled red cells were carried out on 15 patients with soft tissue tumors. There was no correlation between blood flow or pooling and the degree of Tc-99m DTPA uptake by the palpable masses. The sensitivity of DTPA uptake as indicative of nonlipomatous tissue was 100%, and its specificity was 91%. The predictive probability that a lesion was a liopoma if there was no DTPA uptake at any phase was 100%. PMID- 1934827 TI - Cerebral blood flow SPECT with Tc-99m exametazine correlates in AIDS dementia complex stages. A preliminary report. AB - Human immunodeficiency virus (HIV) infection is frequently complicated by a variety of disease processes affecting the central nervous system (CNS). One of them is AIDS dementia complex (ADC), which, in the absence of opportunistic infection, is believed to be caused by HIV itself. ADC is characterized by a constellation of cognitive, motor, and behavioral symptoms that progressively get worse. This study was coined to recruit AIDS patients without any opportunistic CNS infection but with signs of CNS abnormality as evidenced by behavioral and subtle motor changes, then to categorize them into five stages, and finally to perform the cerebral blood flow scan using Ceretec. The aim of this study was to correlate the abnormalities of the brain scan with the different stages of ADC. Five patients were analyzed, with dementias ranging from mild to severe according to Price's classification. After confirming the absence of CNS opportunistic infections and AIDS associated malignancies by CT of the brain, the patients underwent psychiatric evaluation and brain scans. The SPECT scans were very sensitive in showing uptake defects in the brain, even in the early stages of ADC. The blood flow defects were more pronounced in the later stages, while the CT scans remained negative except in patients with the most severe dementia. PMID- 1934826 TI - Quantitation of differential renal function with Tc-99m MDP. AB - This study was designed to evaluate the usefulness of the bone tracer Tc-99m MDP for quantitative assessment of relative renal function as compared with renal imaging radiotracers used for that purpose. Differential renal function, i.e., the percent contribution each kidney makes to global renal function, was determined prospectively in 15 consecutive patients using Tc-99m MDP and a renal radionuclide tracer, either Tc-99m DTPA or Tc-99m GHA. Differential function was computed in all cases from the early (1-3 minutes) renal uptake of the tracers by region-of-interest analysis of the computer-acquired data. There was a high correlation between values of differential function obtained with Tc-99m MDP and those obtained with Tc-99m DTPA or Tc-99m GHA (r = 0.98, P less than 0.0001). Qualitative assessment of the images revealed equivalent scintigraphic patterns in all patients. It is concluded that the early characteristics of renal handling of Tc-MDP are sufficiently similar to those of Tc-DTPA and Tc-GHA so that accurate estimates of differential renal function are possible with this agent, and that Tc-MDP-determined renal differential most likely reflects differential glomerular filtration rate. PMID- 1934828 TI - Tc-99m HMPAO SPECT analysis of neuroleptic effects on regional brain function. AB - This report describes a new approach to the evaluation of neuroleptic effects on regional brain function. Using Tc-99m HMPAO SPECT imaging, consecutive brain perfusion studies before and after acute haloperidol administration were performed on three schizophrenic patients and two normal volunteers. The antipsychotic drug ameliorated the hypoactivity in the frontal lobe and suppressed the hyperactivity in the temporo-occipito-parietal lobe selectively in the dominant hemisphere in the schizophrenic patients. It did not exert a significant influence on the brain perfusion pattern in normal volunteers. This nuclear medicine technique seems to be useful for the evaluation of drug effects in psychiatric diseases. PMID- 1934829 TI - Tc-99m HMPAO SPECT imaging of the central nervous system in tuberous sclerosis. AB - Tc-99m HMPAO was used to evaluate cerebral perfusion in a patient with tuberous sclerosis. The SPECT images demonstrated reduced HMPAO uptake in regions corresponding with MRI-confirmed locations of cortical tubers. These results indicate that the lesions are characterized by vascular perfusion deficits and support the hypothesis that cortical tubers result from developmental abnormalities of the embryonic central nervous system. PMID- 1934830 TI - Tc-99m HMPAO diffuse pulmonary uptake demonstrated in cigarette smokers. AB - Tc-99m HMPAO, a lipophilic radiotracer used as a brain SPECT imaging agent in the diagnosis of strokes and dementias, is normally localized in the brain and the heart and is excreted through the kidneys (50%) and the hepatobiliary system (14% to 30%). There is no pulmonary localization except in the lungs of smokers. To evaluate pulmonary localization of Tc-99m HMPAO in relation to smoking, 23 patients (aged 27 to 76 years) who were referred for brain imaging studies for strokes or dementias also underwent lung imaging studies immediately following the brain imaging. Anterior and/or posterior lung images were obtained 30 to 45 minutes after IV injection of 15 mCi Tc-99m HMPAO. Diffuse pulmonary uptake was graded semiquantitatively: 3+, pulmonary uptake is equal to or higher than hepatic uptake; 2+, pulmonary uptake is less than hepatic uptake but higher than cardiac uptake; 1+, pulmonary uptake is equal to cardiac uptake; 0, pulmonary uptake is less than cardiac uptake. Each patient's smoking history, including duration and daily consumption, was recorded. Four patients' lung images showed 3+ lung uptake; 6 patients, 2+; 1 patient, 1+; and 12 patients, 0 uptake. Eleven patients with lung uptakes of 3+ to 1+ had a history of cigarette smoking. Twelve patients with lung uptake less than cardiac uptake had no smoking history. Pulmonary distribution of Tc-99m HMPAO is usually negligible in the normal lung. Our results indicate that lung uptake correlates significantly (chi-square = 23, d.f. = 1, P = 0.0001) with smoking history. PMID- 1934831 TI - Tc-99m MDP appearance and resolution in a cerebral infarct in a patient with dementia. PMID- 1934832 TI - Bile leak from choledochal cyst in a child. PMID- 1934833 TI - SLE-related choroidopathy depicted by In-111 leukocyte imaging. PMID- 1934834 TI - Primary hyperoxaluria type 1. Bone scintigraphy, X-ray radiography, and gamma-ray quantitative CT. PMID- 1934835 TI - Hepatobiliary scan appearance of heterotopic liver transplantation. PMID- 1934836 TI - Scintigraphic changes in physis in osteomyelitis. PMID- 1934837 TI - Abnormal Tc-99m MDP accumulation in a pyelocaliceal diverticulum. PMID- 1934838 TI - Localization of radionuclide bone agent in a perigastric leiomyomatous tumor. PMID- 1934839 TI - A treatment protocol of the acute asthma patient in a pediatric emergency department. AB - A treatment protocol for pediatric patients with acute asthma from 8 months to 15 years of age was utilized in an urban pediatric emergency department. In a three month period, 682 children were evaluated with acute asthma with 566 (83.0%) initially discharged and 116 (17.0%) admitted. There were no deaths. Treatment included aerosol inhalation in 682 patients (100%) and both intravenous steroids and aminophylline in 247 (36.2%) patients. Medical care was rendered by housestaff physicians supervised by full-time attending physicians. Of the 566 patients discharged, 131 (21.1%) patients had received intravenous aminophylline and steroids. Of those discharged 14 (2.5%) were admitted during the subsequent 48 hours for status asthmaticus. Of the 247 patients who received intravenous medications, chest radiographs consistent with pneumonia were noted in 15 (6.2%). The routine use of this protocol has been effective in the short term emergency department management of pediatric patients with acute asthma and had been accepted by the housestaff and attending physicians. PMID- 1934840 TI - Differential diagnosis and treatment of conversion disorder and Guillain-Barre syndrome. AB - Three cases are presented which illustrate the possible difficulties in differentiating between the diagnoses of Guillain-Barre Syndrome and conversion disorder. Accepted criteria are specified for each condition, as well as some associated features often characteristic of similar cases. Supportive interdisciplinary treatment for Guillain-Barre Syndrome is reviewed, and an interdisciplinary multi-modal approach to treatment of conversion disorder is described. PMID- 1934841 TI - Maternal parenting stress in physicians' families. AB - The families of 16 male staff physicians and 26 male residents were studied. All spouses completed the Abidin Parenting Stress Index (PSI) prior to a well-child visit. Home interviews were conducted to identify factors contributing to stress. PSI scores were similar in both groups. The interviews suggested that physician fathers had limited time and energy for parenting. Resident fathers were twice as likely as staff fathers to participate in child care when home. Parenting stress tended to stay the same in 25% of families or increased in 50% of families after residency training. PMID- 1934842 TI - Endocardial fibroelastosis with coronary artery thromboembolus and myocardial infarction. AB - We report a case of an 18-month-old male, born to a woman with third trimester febrile illness, who had a history of congestive heart failure and respiratory distress, cardiomegaly, and electrocardiographic (ECG) findings suggestive of cardiomyopathy and myocarditis. After gradual improvement in heart size and function with pharmacologic therapy, he developed a terminal episode of respiratory distress and cardiogenic shock, with ECG findings of an anterolateral infarct. At autopsy it was found that endocardial fibroelastosis with mural thrombi in the left ventricle had been complicated by thromboembolism to the left anterior descending coronary artery, resulting in transmural infarction of the anteroseptal region of the left ventricle. Myocardial infarction is a potential but unusual thromboembolic complication of endocardial fibroelastosis. A high index of suspicion for coronary artery thromboemboli should be maintained in pediatric patients with cardiomyopathy and suspected myocardial infarction. PMID- 1934844 TI - Tympanic thermometry. PMID- 1934843 TI - Pseudohypoaldosteronism: successful treatment with home electrolyte monitoring. PMID- 1934845 TI - Response of patients with myelofibrosis to megadose methylprednisolone. PMID- 1934846 TI - Tuberculous iridocyclitis in a three-year-old girl. PMID- 1934847 TI - Biomedical technology: to use or not to use? AB - The past 30 years have seen tremendous advances in biomedical technology that have changed dramatically the practice of medicine in general, of neonatology in particular. All changes have not been for the best, however. The price tag has been especially steep, but there have been adverse effects on the quality of medicine as well. The reasons we rely on high technology, its risks and pitfalls, and our future handling of decisions regarding using or not using biotechnology deserve careful consideration, including financial factors that physicians have been loath traditionally to address. If the medical profession is to avoid becoming enslaved to technology, our future decisions must be better informed, more rational, and based on more scientific facts than they have been in the past. Above all, physicians must avoid becoming mere technicians at the expense of the traditional humanistic approach to patient care. PMID- 1934848 TI - Newer technologies and the neonate. PMID- 1934849 TI - Thermoregulation: incubators, radiant warmers, artificial skins, and body hoods. AB - Keeping babies warm whether using incubator or radiant warmers is important in optimizing their chances of survival. Many design changes have occurred in devices for keeping babies warm, while few controlled studies using clinically important end points have been conducted to assess these changes. Radiant warmers produce larger evaporative heat and water losses and slightly higher basal metabolic rate than incubators. The clinical significance of the higher metabolic rate is uncertain. The water losses create an additional problem in managing infants under radiant warmers. The use of hoods made of thin plastic films to raise local humidity and reduce evaporative water loss helps control this problem. In incubators, humidity may be necessary to provide a warm enough environment for the most immature infants. Artificial skins as yet have not supplanted body hoods for this purpose. Both incubators and radiant warmers produce temperature instability when used as skin servocontrolled devices. There are, however, no data currently available to say how much thermal instability can be well tolerated by a baby. Too much thermal instability produces apnea and increased mortality. Air servocontrolling an incubator reduces environmental temperature instability. PMID- 1934850 TI - Phototherapy for neonatal jaundice. AB - Phototherapy is now the preferred method of treatment for neonatal hyperbilirubinemia by virtue of its noninvasive nature and its relative freedom from major complications. It is also convenient, easy to use, and inexpensive in terms of personnel, equipment, and disposals. Long-term experience with phototherapy has demonstrated its safety as well as efficacy. With high-intensity phototherapy at saturation dose, even severe hemolytic hyperbilirubinemia can be adequately controlled; only pack-cell transfusions are required to correct the resulting anemia. It should be stressed, however, that adequate monitoring of the well-being of the baby together with the bilirubin levels should always be observed carefully. The lamps should be kept cool during phototherapy and be changed regularly after every 2000 hours of use. Observing such precautions will ensure the efficacy and safety of phototherapy. PMID- 1934852 TI - Cardiorespiratory monitoring. AB - Documented monitoring has many actual or potential advantages compared to undocumented monitoring. Due to the occurrence of monitor alarms in virtually all monitored infants and the potential for undue parental concern or noncompliance when excessive false alarms do occur, documented monitoring needs to become the standard for home electronic surveillance. The increased cost should be more than offset by net reductions in total duration of home monitoring and will be minimized by the integration of the home monitor and event recording components. Documented monitoring will quantify the frequency, duration, and type of each true event, whether related to apnea, bradycardia, desaturation, or a combination thereof. The availability of routine documented monitoring including SaO2 will be of dramatic benefit in enhancing our understanding regarding the pathophysiology of apparent life-threatening events and sudden death, providing the clinician with a heretofore unavailable powerful diagnostic and therapeutic modality. PMID- 1934851 TI - Pulse oximetry in neonatal medicine. AB - The safety, accuracy, reliability, noninvasiveness, and ease of use make pulse oximetry a valuable addition to oxygen monitoring of infants in special care nurseries. Such instruments are less sensitive to changes in peripheral circulation or to edema, making them more reliable in sick, physiologically unstable babies and in chronically ill babies with bronchopulmonary dysplasia. In these infants, rapid and accurate measurements of oxygen saturation with such instruments can promote optimal ventilator and oxygen management. In addition, observation of changes in oxygenation during various aspects of care can help optimize care plans for each infant. Although there remains a need for knowing PO2 in preterm infants, pulse oxygen saturation monitoring adds an important degree of control of oxygen management. PMID- 1934853 TI - Evoked potential assessment of auditory system integrity in infants. AB - One child in 750 is born with a handicapping hearing impairment. The methods available to screen and evaluate infants at risk (auditory brainstem responses, middle latency responses, and cortical auditory evoked potentials) are reviewed, explained, and illustrated with case histories. PMID- 1934854 TI - Magnetic resonance spectroscopy. AB - MRS is a noninvasive technique that does not use ionizing radiation and can be used to measure relative metabolite concentrations in human tissues and organs in vivo. Phosphorus MRS can be used to study energy metabolites and intracellular pH. The first neonatal applications were described in 1983 in a study of cerebral metabolism. Since then, the value of cerebral MRS as research tool and an investigative technique has been confirmed, and its prognostic power in asphyxiated infants has been established. Techniques of spatial localization and quantitation have been developed, but studies of other organs and the use of other nuclei remain at a very preliminary stage. Considering the huge potential of MRS and the proliferation of high field magnets primarily designed for imaging, there has been a disappointing lack of progress in the development of clinical and research applications of spectroscopy. The logistic differences of studying sick infants in strong magnetic fields make MRS a time-consuming and labor-intensive investigation, which will inevitably limit its widespread routine use. Research studies are hampered by the diversity of spectroscopic and signal processing techniques, which make comparisons of data from different groups impossible. Some techniques for the assessment of cerebral hemodynamics such as doppler ultrasound and near infrared spectroscopy have the advantage of being available at the cotside, but MRS is unique in providing quantitative information about a wide range of intracellular metabolites. The altricial development of MRS as a clinical investigative tool in neonatology can be ascribed partly to practical difficulties, but these should not detract from the exciting possibilities opened up by a technique that gives a noninvasive insight into intracellular chemistry. The metabolic information from MRS is an invaluable addition to the information provided by other techniques and will certainly play an important role in unraveling the sequence of events between an hypoxic ischemic insult and cell death. A better understanding of these mechanisms is a prerequisite to the development of rational therapeutic maneuvers following asphyxial insults. PMID- 1934855 TI - Positron emission tomography in newborn infants. AB - Positron emission tomography (PET) is a technique that permits the noninvasive in vivo measurement of a variety of cerebral physiologic and biochemical processes. Numerous complex methodologic and technical features must be considered when PET is applied to the study of the newborn's cerebral physiology and neurologic disease. Although the application of PET to newborn infants is still in its formative stages, important information regarding perturbations of cerebral blood flow in neurologic diseases has been obtained and striking developmental changes in cerebral metabolism are apparent. PMID- 1934856 TI - High-frequency ventilation: issues of strategy. AB - Although each high-frequency ventilator has functional characteristics that are design related, it now appears that when used with similar treatment strategies and within their functional limitations, similar clinical outcomes can be realized. Optimized treatment protocols must vary depending on the pulmonary disease to be treated, with strategies during treatment for pulmonary injury different from those used in pulmonary injury prevention. It is still unclear whether any one particular high-frequency ventilator will have specific disadvantages that cannot be overcome by device modification and that are inherent in a particular HFV methodology. Experimental and clinical data suggest that HFV will contribute significantly in reducing neonatal pulmonary morbidity and aid in the prevention of chronic pulmonary disease. PMID- 1934857 TI - Measurement and monitoring of pulmonary function. AB - Several computerized systems that allow the collection of data for measurements of pulmonary function have been developed. Although many of these systems eliminate distorted and incomplete breaths from the analysis, there are still many possibilities for error secondary to the inexperience of the user or to patient-related factors. Training and experience with the use of these instruments is essential to obtain reliable results. A clear understanding of all the principles, the assumptions, and limitations affecting the measurements is also essential. The methodology underlying these systems is reviewed. In addition, the commercially available equipment needs to be standardized from an engineering point of view, to assure that the components used have the proper frequency response, that the signals are collected at proper rates, that calibration is simple and accurate, and that the analysis of the data is correct. Systems should be standardized against a lung model. PMID- 1934858 TI - Total body electrical conductivity measurements in the neonate. AB - TOBEC measurements are based on the premise that a conductive object will interact with an electromagnetic field and result in the dissipation of a small quantity of the field's energy. TOBEC instruments provide a measure of this energy loss, which for a given conductor varies according to its size. The conductive component of the body is that part that contains water with dissolved electrolytes, i.e., essentially the FFM. Fat, by definition, is anhydrous and does not contribute to a TOBEC measurement. To interpret TOBEC readings in terms of the quantity of FFM in the body requires the use of a calibration equation that is generated by measuring the FFM of a reference population using an alternative technique and relating this to each individual's TOBEC value. Because no alternative method exists to estimate the FFM of an infant, a calibration equation is used that was generated from measurements of young miniature piglets. The body composition of infants thus derived is consistent with our general understanding of the changes in fat and FFM in human infants in early life. Whether TOBEC can be used as described in premature or older children has yet to be determined. Variations in the composition of the FFM do not seem to compromise the accuracy of the technique. TOBEC measurements are precise, rapid, noninvasive, and safe and cause the subject no discomfort. These features not only make TOBEC a useful tool for the nutritional assessment of a pediatric patient but they also may be a useful diagnostic tool for the clinician. PMID- 1934859 TI - Detection of prenatal drug exposure in the pregnant women and her newborn infant. AB - Although urine testing remains the standard method for identifying and monitoring drug addicts, recent data suggest that it seriously underdiagnoses the prevalence of fetal exposure to various drugs. Results obtained with other body fluids and tissues (meconium and hair) are reviewed and the laboratory methodologies used to detect drugs are discussed in details. PMID- 1934860 TI - New drug development in the United States from 1963 to 1990. PMID- 1934861 TI - Effect of neurotrauma on hepatic drug clearance. AB - Lorazepam, antipyrine, and indocyanine green were administered to 10 patients with severe head injuries as marker substrates of hepatic glucuronidation, oxidation, and hepatic blood flow, respectively. Pharmacokinetic parameter estimates were determined at baseline (20 to 80 hours after injury) and up to three additional times thereafter (study days 4, 7, and 14). Antipyrine clearance was increased significantly from baseline (0.50 +/- 0.31 ml/min/kg) on study days 4, 7, and 14 (p less than 0.0001). Increases in antipyrine clearance from baseline to the last study day were observed in all study patients ranging from 14% to 207%. A significant increase was also observed in lorazepam clearance on study day 14 relative to baseline (1.39 +/- 0.56 ml/min/kg) (p less than 0.005). Increases in lorazepam clearance occurred in seven of nine patients over time ranging from 9% to 130%. The unbound fraction of lorazepam did not change significantly over the study period. Likewise, no significant change was observed in the clearance of indocyanine green over time. Antipyrine clearance and alpha 1 acid glycoprotein (r = 0.41), and lorazepam clearance and C-reactive protein (r = -0.38) were significantly correlated (p less than 0.05). Similarly, antipyrine and lorazepam clearances were significantly correlated with injury severity based on the Acute Physiologic and Chronic Health Evaluation (APACHE II) score (r = 0.43 and r = -0.37, respectively). These findings suggest that hepatic oxidative and conjugative metabolism increase significantly over time in patients after acute head injury. An awareness of the potential for pharmacokinetic alterations in similarly metabolized drugs used for patients with severe head injuries is recommended. PMID- 1934862 TI - Interference of dairy products with the absorption of ciprofloxacin. AB - The effects of milk and yogurt on the bioavailability of ciprofloxacin were studied in seven healthy volunteers in a randomized crossover trial. After an overnight fast, 500 mg ciprofloxacin was given with 300 ml water, milk, or yogurt. Plasma ciprofloxacin concentrations were significantly (p less than 0.05) lower during the milk and yogurt phases from 1/2 to 10 hours; at 1/2 hour the concentration was reduced by 70% by milk and by 92% by yogurt. Milk reduced the peak plasma concentration by 36% (p less than 0.05) and yogurt by 47% (p less than 0.05). The extent of bioavailability, measured as the total area under the plasma concentration-time curve and 24-hour urinary excretion of ciprofloxacin, was reduced by 30% to 36% by milk and yogurt (p less than 0.05). We conclude that the absorption of ciprofloxacin can be reduced by concomitant ingestion of milk or yogurt. To avoid therapeutic failures in infections where the causative organism is only moderately susceptible, ingestion of large amounts of dairy products in liquid form with ciprofloxacin is not recommended. PMID- 1934863 TI - Food-induced reduction in bioavailability of didanosine. AB - The effect of food on the pharmacokinetics of didanosine was evaluated in an open two-way crossover study in eight male subjects who tested seropositive for the human immunodeficiency virus. Each subject received a single 375 mg oral dose of didanosine in a chewable tablet form with or without food. Serial blood samples and the total urinary output during 12 hours were collected and assayed for intact didanosine by validated HPLC methods. The mean (SD) values for the peak concentration (Cmax) of didanosine in plasma were 2789 (1032) ng/ml and 1291 (536) ng/ml and for the area under the plasma concentration-time curves (AUC0 infinity) were 3902 (1316) and 2083 (922) hr.ng/ml, and the urinary excretion (%UR) accounted for 21% and 11% of dose as intact didanosine when didanosine was given under fasting conditions and with food, respectively. The values of Cmax, AUC0-infinity, and %UR were significantly lower for subjects who received didanosine with food compared with those observed for the fasted subjects. The time to reach Cmax, mean residence time, elimination half-life, and renal clearance remained essentially the same between the two treatments. The results from this study indicated that the rates of absorption and elimination were not affected by the presence of food; however, the extent of absorption, as indicated by AUC0-infinity and %UR, was reduced significantly in the presence of food. It is recommended that didanosine be administered under fasting conditions. PMID- 1934864 TI - Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. AB - Caffeine was used as a metabolic probe to screen healthy subjects for their activities of two enzymes, deduced to be CYP1A2 (an inducible cytochrome P450) and xanthine oxidase. A longitudinal study revealed modest effects of caffeine dose, ethanol intake, and time-of-day on the CYP1A2 index, without any effect on the xanthine oxidase index. The coefficients of intraindividual variation not accounted for were 5.0% for the xanthine oxidase and 17.2% for the CYP1A2 index. In a population study, both indexes showed a log normal distribution, with CYP1A2 values of most subjects covering a 6.3-fold range but only a 1.7-fold range with xanthine oxidase. The CYP1A2 index was 33% decreased in women who used oral contraceptives and substantially increased in cigarette smokers. Neither the CYP1A2 nor the xanthine oxidase index differed between volunteers of Chinese and European extraction. Four of 178 subjects showed unexplained low xanthine oxidase values (i.e., values several standard deviations below the mean). PMID- 1934866 TI - Dose-dependent inhibition of the hemodynamic response to dipyridamole by caffeine. AB - We investigated the effects of the adenosine antagonist caffeine on the hemodynamic response to dipyridamole infusion (0.4 mg/kg for 4 minutes). According to a randomized, placebo-controlled double-blind protocol, eight normotensive volunteers each participated in five tests: placebo after placebo, dipyridamole after placebo, and dipyridamole after 1, 2, and 4 mg/kg caffeine. Infusion of caffeine alone (4 mg/kg) induced an increase in mean arterial pressure of 6.1 +/- 0.5 mm Hg versus 1.5 +/- 0.9 mm Hg after placebo (p less than 0.05). Infusion of dipyridamole alone exerted a characteristic hemodynamic response with an increase in systolic blood pressure (+8.4 +/- 2.4 mm Hg), pulse pressure (+7.0 +/- 2.4 mm Hg), heart rate (+25.7 +/- 3.8 beats/min) and calculated rate-pressure product (+3419 mm Hg x beats per minute), all being significantly different from the changes induced by placebo. Caffeine induced a dose-dependent attenuation of the response to dipyridamole, with a significant negative correlation between the dose of caffeine on the one hand (0, 1, 2, and 4 mg/kg) and the dipyridamole-induced increments in systolic blood pressure (r = 0.53), pulse pressure (r = -0.50), heart rate (r = -0.95), and rate-pressure product (r = -0.93) on the other hand. We conclude that caffeine attenuates the hemodynamic response to dipyridamole infusion in humans in a dose-dependent fashion. Because of the wide-spread use of caffeine, this pharmacologic interaction may be of clinical importance, for example, in the diagnostic use of dipyridamole in thallium-201 myocardial imaging. PMID- 1934865 TI - Differential effects of quinidine on the disposition of nifedipine, sparteine, and mephenytoin in humans. AB - The effects of quinidine on oxidative routes of drug metabolism mediated by different forms of cytochrome P450 were investigated in 10 healthy subjects. Each subject was studied on three different occasions and separately received oral administration of (1) a "cocktail" of nifedipine (5 mg), sparteine sulfate (90 mg), and mephenytoin (100 mg), (2) quinidine sulfate (200 mg), and (3) quinidine sulfate followed by the "cocktail" 1 hour later. Quinidine pretreatment significantly inhibited the aromatization of nifedipine to its major first-pass pyridine metabolite (M-0) and prolonged the elimination half-life of the calcium channel antagonist, both by about 40%. More marked inhibition of metabolism was observed with sparteine, and the formation of dehydrosparteine was abolished. A significant correlation was found between the 0-8-hour urinary ratio and the plasma concentration ratio of sparteine to dehydrosparteine obtained 4 hours after drug administration. No quinidine-induced changes were observed in the 4 hydroxylation of mephenytoin. The interaction between quinidine and nifedipine supports the involvement of a common P450 (P450IIIA4) in the metabolism of the two drugs. PMID- 1934867 TI - Effects of fish oil and endorphins on the cold pressor test in hypertension. AB - The effects of fish oil and naloxone on blood pressure, catecholamines, and endorphins during the cold pressor test were evaluated in a randomized, double blind, placebo-controlled, two-way crossover trial of normotensive and medication free hypertensive men (n = 13 each). Subjects were given 5 gm omega-3 fatty acids per day or placebo for 30 days with a 1-month washout between interventions. The cold pressor test (hand in ice water for 5 minutes) was done at the end of the treatment periods. Intravenous naloxone (10 mg) or placebo was given before the cold pressor test. Fish oil-treated, normotensive, or hypertensive groups had similar changes in blood pressure, plasma catecholamine levels, and beta endorphins during the cold pressor test, but naloxone treatment was associated with fivefold and tenfold increases in plasma epinephrine and cortisol levels, respectively. Naloxone may modulate sympathomedullary discharge through blockade of endorphin activity. It is unlikely that endorphins are involved in the blood pressure increase during the cold pressor test or that fish oil alters this response. PMID- 1934868 TI - Homocysteine levels in patients with rheumatoid arthritis treated with low-dose methotrexate. AB - Plasma homocysteine levels were determined in patients who participated in a randomized, double-blind placebo-controlled trial of folate supplementation (1 mg/day) during methotrexate therapy for rheumatoid arthritis. Plasma and red blood cell folate levels before methotrexate therapy were significantly negatively correlated with homocysteine levels. Homocysteine levels were not significantly correlated with the initial C1 index (an assay that measures the folate status of blood mononuclear cells) or the C1 index during methotrexate therapy. There was no significant difference in homocysteine levels between pretreatment and levels drawn at 3 or 6 months. Initial homocysteine levels were predictive of toxicities, such as gastrointestinal intolerance and elevations of liver enzymes in the placebo group. There was no significant correlation between occurrence of toxicity and initial homocysteine levels in the folic acid supplemented group. Homocysteine levels were not predictive of the efficacy of methotrexate therapy. We conclude that plasma homocysteine levels are correlated with plasma and red blood cell folate levels before methotrexate therapy but is not correlated with folate status in blood mononuclear cells. PMID- 1934869 TI - Muzolimine: renal site of action and interaction with probenecid in humans. AB - Muzolimine (60 mg, administered orally) was administered to eight healthy volunteers, under conditions of altered fluid load, to elucidate its renal site of action. The duration of action and the effect of probenecid pretreatment on muzolimine response was also investigated. Muzolimine had a rapid onset of action, with the diuresis complete within 4 hours after dosing. At peak natriuresis, under hydrated conditions, fractional excretion of free water remained unaltered (9.72% +/- 0.59% versus 9.07% +/- 0.44%; difference not significant) but was accompanied by a significant increase in the delivery of sodium out of the proximal tubule, as measured by fractional excretion of lithium (22% +/- 2% to 31% +/- 1%; p less than 0.01). The fraction of sodium reabsorbed in the distal tubule also decreased from 94% +/- 1% to 67% +/- 1% (p less than 0.001) of the delivered load. The fractional reabsorption of free water during hydropenia decreased after muzolimine (5.63% +/- 0.26% to 2.00% +/- 0.81%; p less than 0.05). Pretreatment with probenecid resulted in a prominent decrease in urinary sodium excretion (246 +/- 25 mmol/24 hr for muzolimine alone 161 +/- 24 mmol/24 hr for muzolimine and probenecid; p less than 0.01). These findings suggest that muzolimine has a major site of action in the medullary portion of the thick ascending limb of Henle with additional inhibitory activity on the proximal tubule. It is likely that the active secretion of one or more of the acidic metabolites of muzolimine, by way of the probenecid sensitive organic acid pathway, is responsible for mediating the renal actions this basic drug. PMID- 1934870 TI - Paradoxical relationship between acetylator phenotype and amonafide toxicity. AB - Patients receiving the investigational antineoplastic agent amonafide underwent prospective determination of acetylator phenotype with use of caffeine as a test drug. Fast acetylators of caffeine had significantly greater toxicity (myelosuppression) after amonafide treatment than slow acetylators, presumably because of greater conversion of amonafide to the active acetylated metabolite. Furthermore, the estimated area under the plasma concentration-time curve of amonafide was significantly greater in the fast acetylators, indicating that the total plasma clearance was paradoxically lower in this group. It is hypothesized that this paradox is attributable to competition for oxidation of amonafide by its acetylated metabolite (parallel pathway interaction). Pretreatment white blood count and patient age were also independent predictors of leukopenia. In addition, it was noted that the ratio of actual to ideal body weight was significantly higher in the fast acetylators. Studies are in progress to determine the optimal amonafide dose in both acetylator subgroups. PMID- 1934872 TI - Workshop on drug utilization review. Introduction. PMID- 1934871 TI - Facilitating prompt diagnosis and treatment of the neuroleptic malignant syndrome. PMID- 1934873 TI - Workshop on drug utilization review. Rockville, Maryland, November 26-27, 1990. Proceedings. PMID- 1934874 TI - The definition of drug utilization review: statement of issues. PMID- 1934875 TI - Development of criteria for drug utilization review. PMID- 1934876 TI - Workshop on drug utilization review. What the government wants. PMID- 1934877 TI - A congressional perspective on inappropriate drug therapy and drug utilization review. PMID- 1934878 TI - Workshop on drug utilization review. A practitioner's point of view. PMID- 1934879 TI - Drug utilization review in the 1990s. PMID- 1934880 TI - Drug utilization review: state of the art from an academic perspective. PMID- 1934881 TI - A view from the drug utilization review management organization sector. PMID- 1934882 TI - Panel I. Drug utilization review: criteria. PMID- 1934883 TI - Panel III. Intervention: the use of drug utilization review outcomes. PMID- 1934884 TI - Panel IV. Evaluation: the value and cost-effectiveness of drug utilization review programs. PMID- 1934886 TI - Male aesthetic surgery. PMID- 1934885 TI - The male foreheadplasty. Recognizing and treating aging in the upper face. AB - Many surgeons remain mistakenly preoccupied with aging in the jowl and neck and often overlook more objectionable changes in the upper face. These changes produce not only an old or aged appearance but also inappropriate expressions. This article outlines the elements of aging in the upper face and details the planning and execution of the foreheadplasty. Topics discussed include upper facial aesthetics, pseudoblepharochalasis, incisions for bald or balding men, and techniques for minimizing scars. PMID- 1934887 TI - Periorbital aesthetic surgery for men. Eyelids and related structures. AB - This article has provided an overview of recent advances and contemporary philosophy in male blepharoplasty and aesthetic periorbital surgery. It has emphasized the importance of proper brow positioning, invagination procedures on the upper lid with minimal skin excision, restoration of tone in the lower lid without deforming the aperture, designing skin and muscle excisions to prevent deformity, and repair of the deforming tear trough or nasal-jugal ditch through an extremely helpful new tear trough implant. PMID- 1934888 TI - Implants for male aesthetic surgery. AB - Male aesthetic surgery is rapidly becoming more popular. Increasing emphasis is being placed on facial skeletal contour. Prominent cheek bone and jaw line structure are highly desirable male characteristics. Newer anatomic designs for malar and premandible implants now exist and can be utilized with minimal risk. Following zonal principles of facial skeletal anatomy greatly enhances precision and predictability of result and form. PMID- 1934889 TI - Rhinoplasty and the male patient. AB - A review of male patients undergoing rhinoplasty indicates a surprising diversity of anatomy and especially skin coverage. When compared with rhinoplasty in the female adolescent, the goal must be more of a "balanced rhinoplasty" rather than a reductive rhinoplasty, and the techniques required are more diverse. Careful screening of patients is essential to eliminate a subgroup of men with severe psychologic obsessions. PMID- 1934890 TI - Secondary rhinoplasties for men. AB - The result of secondary rhinoplasties in men must be absolutely natural. The dorsum, the tip's elevation, and the diverse angles that the nose forms with the rest of the face--that is, shape, dimension, and proportion--must be correct. Illustrative cases of the most frequent defects are presented along with ways to prevent them. PMID- 1934891 TI - Treatment of male pattern baldness and postoperative temporal baldness in men. AB - The use of plastic surgery techniques such as flaps and reductions has resulted in dramatic progress in the treatment of baldness. The operative indications are difficult because of the variety of baldness and the multiple techniques available. Surgeons place themselves at a disadvantage by refusing a specific technique, and this may harm the patient. Surgeons should establish a careful plan before undertaking the treatment of a patient, to make maximum use of the techniques that are available. We prefer flaps and reductions to grafts because of the decrease in the number of operations and time required to obtain a good result. We have described our personal classification, which takes into account the distribution of the hair, the density in each region, and the position of the frontal and temporal hairlines. This enables us to be more precise as to the indications and limitations of surgery. Different modern techniques have been described, concentrating on major reductions or scalp lifts as described by the author, which results in advancement of the crown 6 cm posteriorly and between 2 and 3 cm laterally. Dramatic results can be obtained if one or two vertical flaps are raised during the same operation. Vertical flaps provide a better result than horizontal flaps because they provide a deep android recession and natural forward hair growth. These techniques have the advantage of providing a rapid and aesthetic result after each operation as compared with punch grafts, which require long periods of time before obtaining a reasonable result. Finally, we propose a rapid, easy, two-stage procedure for extensive baldness that combines a one-stage preauricular flap with a scalp lift. The aesthetic result is good and may be completed by another reduction or by punch grafts. PMID- 1934892 TI - Microsurgical free temporoparietal flaps in surgery for male pattern baldness. AB - A method known as the microsurgical free temporoparietal flap transfer for restoring the anterior hairline has been described. With the use of this technique, the grafted hair should have a natural hair direction, and the grafted hair exhibits a normal appearance after surgery to correct baldness. PMID- 1934893 TI - Male body contouring. AB - Male body contouring is discussed in regard to indications and patient selection. General guidelines are given for anesthesia, positioning, preoperative marking, and operating room preparation. The technique is discussed for facial, chest, and abdominal contouring. Suction lipoplasty, abdominoplasty, flankplasty, and thigh contouring are discussed in detail. PMID- 1934894 TI - Gynecomastia. Liposuction and excision. AB - Lipoplasty has facilitated the correction of gynecomastia and improved the morbidity and end results. The author details his technique of combining lipoplasty with excision for gynecomastia. PMID- 1934895 TI - Male chest correction. Pectoral implants and gynecomastia. AB - Implants have been developed in different sizes and shapes to mimic the pectoralis major muscle and its nipple-areolar complex below it. These soft, solid silicone implants have the approximate dimensions in height, length, and thickness as the muscle the implant is to mimic. Some improvements in the treatment of breast hypertrophy have also allowed a better result in the surgery of gynecomastia. The challenge of obtaining a smooth and flat result has been helped by the technique of liposuction with circum-areolar excision. PMID- 1934896 TI - Alloplastic implants for men. AB - Recent advances in medical grade elastomer technology empower plastic surgeons to enhance specific body parts, thereby performing body sculpting. This article examines alloplastic implants for large body soft-tissue augmentation, namely pectoralis major enlargement, calf augmentation, and buttock enhancement. PMID- 1934897 TI - Calf contour correction with implants. AB - Implants have been developed in a shape allowing mimicking of the muscle while they are placed on top of it, thus giving a natural appearance to the leg. The author presents a satisfactory technique of calf implantation and its potential, although uncommon, problems. PMID- 1934899 TI - Physician-administered office anesthesia. AB - Surgeons who administer office anesthesia accept a serious responsibility for the well-being of their patients. Each must be thoroughly familiar with the agents they employ and prepared to deal with any complications or untoward events that might arise out of their use. Patients who are healthy or have well-controlled mild systemic disease are generally suitable for office procedures. Overly apprehensive patients, those with a history of anesthetic difficulties, or any patient with significant medical problems should be provided an anesthesiologist or competent Certified Registered Nurse Anesthetist (CRNA). It is irresponsible and dangerous to administer anesthesia in a substandard facility or with an inadequate or inexperienced staff. All staff members should be BCLS (Basic Cardiac Life Support) qualified, and key individuals should be encouraged to obtain ACLS (Advanced Cardiac Life Support) certification. Proper pharmacologic preparation of the patient will allay anxiety, increase comfort, and reduce the overall quantity of anesthetic needed. Particularly useful agents include benzodiazepines (Valium and Versed) and diphenhydramine (Benadryl). Medication is not, however, a substitute for human contact, genuine concern, or timely reassurance. All patients receiving anything more than a small quantity of local anesthetic should be monitored by transcutaneous pulse oximetry, noninvasive sphygmomanometry, and real-time electrocardiography. Each provides important information on the patient's physiologic condition. Of these three monitors, the most important information is provided by the pulse oximeter. It is capable of detecting a problem before serious physiologic compromise has occurred and should be considered an indispensible part of each patient's care. A brief period of deep sedation for the administration of local anesthetic can safely be achieved using carefully titrated quantities of the short-acting barbiturate methohexital (Brevital). Gauging the proper end point of methohexital administration is accomplished through skilled observation of the patient. As the proper threshold is reached, a characteristic slackening of the jaw occurs usually in conjunction with a distinctive relaxation of the face. In the majority of cases, no change in the SaO2 will occur.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1934898 TI - Anesthesia for male aesthetic surgery. AB - The male patient for aesthetic plastic surgery should expect to have a good experience, with few, if any complications from anesthesia. Proper planning is essential to the process, from setting up the surgical facility to selection and preparation of patients. Anesthetic techniques should be adapted to the needs of each patient, with his safety and comfort the most important consideration. Anesthesia for plastic surgery has progressed from simple injection of local anesthetics to sophisticated sedation and general endotracheal techniques. Better anesthetic drugs, monitors, and procedures for dealing with complications have made anesthesia a major factor in the advances of the plastic surgery specialty. Male patients frequently have different medical problems than their female counterparts have, including cardiovascular disease, hypertension, and smoking history. Other problems include back discomfort and prostate enlargement, both factors that must be taken into consideration with local sedation anesthesia techniques. The use of basic monitoring equipment has made ambulatory surgery safer for patients and has been instrumental in reduction of medication-related complications. Monitoring standards changed in anesthesia in the late 1980s to include electrocardiogram (EKG), precordial or pretracheal continuous monitoring, blood pressure, and pulse oximetry. In addition, if general anesthesia is used, end-tidal carbon dioxide and temperature monitoring and oxygen analysis of the anesthesia gases are also recommended. General anesthesia is being utilized more frequently in cosmetic surgery procedures and offers many advantages over local and conscious sedation techniques. The modern agents and techniques permit the patient to recover quickly, with minimum postoperative sequelae, and provide obvious comfort during the operative procedure. The traditional anesthesia technique for facial plastic surgery has been local anesthesia supplemented by sedation. This technique requires a combination of skillful local administration, selection of appropriate sedation drugs in proper doses, and a cooperative patient. Ideally, the selection and administration of drugs and monitoring of the patient should be by an anesthetist, who understands drug interactions and synergistic and additive effects of sedation drugs. Facility set-up, professional personnel, and recovery and discharge criteria are essential to good anesthesia care for the male aesthetic patient. PMID- 1934900 TI - New foundations for young investigators. PMID- 1934901 TI - Federal science spending priorities: a senator's perspective. PMID- 1934902 TI - The crisis in biomedical research: real but overstated. PMID- 1934903 TI - Attitudes of Colorado physicians toward breast cancer screening for their patients. PMID- 1934904 TI - Changes in immunization requirements. PMID- 1934905 TI - Guidelines for appropriate treatment of managed care plan subscribers requiring emergency medical care. Emergency Medical Care Physician Advisory Committee of the Colorado Medical Society. PMID- 1934906 TI - Colorado's experience. Spinal cord injuries: five years of support and surveillance. PMID- 1934907 TI - VA nurse breaks ground in AIDS treatment. PMID- 1934908 TI - Fractures. Emergency care and complications. PMID- 1934909 TI - Electroencephalographic monitoring in epilepsy. PMID- 1934910 TI - Optical measurements of physiological patellofemoral crepitus. AB - An optical method to measure directly small displacements of the patella has been developed. Light from a helium-neon laser was reflected from a plane mirror taped to the skin over the patella to a glass plate which generated a set of fringes by interference of light reflected from the front and rear surfaces of the plate. The movement of the fringe system was detected using a photodiode. The optical measurements of displacement were compared with those deduced from an accelerometer attached to the same joint. The method was found to be capable of detecting patellar displacements in the range from 20 microns to 180 microns. PMID- 1934911 TI - The fast flush test: evaluation in radial artery catheter-manometer systems. AB - The 'fast flush test' is commonly used to determine the dynamic response of catheter-manometer systems in vivo. We compared the fast flush test with an established bench top test in vitro. The results of the two tests were compared in fifteen underdamped radical artery catheter-manometer systems. There were significant differences between the results, (P less than 0.001 for both resonant frequency and damping factor), and the variance of estimates within measurement systems was significantly greater in the case of the fast flush test (P less than 0.05 and P less than 0.005 for resonant frequency and damping factor respectively). Nevertheless, the differences between the tests were small by comparison with the errors associated with either test; in addition there was a significant linear correlation between the results of the two tests (r = 0.91, P less than 0.001 and r = 0.85, P less than 0.001 for resonant frequency and damping factor respectively). In the in vitro situation, therefore, the fast flush test provides a crude estimate of the dynamic parameters of underdamped catheter-manometer systems. PMID- 1934912 TI - An in vivo area meter for real-time measurement of cross-sectional area in the cardiovascular system. AB - A direct real-time recording of the cross-sectional area of the heart valve is useful for the fluid dynamic study of the cardiovascular system. Electronic circuitry is described that is capable of driving the transmitter coil assembly placed outside the animal and detecting an area-related signal induced in the one turn coil in vivo. When a piece of fine pliable metal thread encircles the area of interest (e.g. the mitral/aortic valve orifice) so as to form a single loop, the electrical potential between the ends of the loop is linearly related to the size of the area irrespective of its shape. The principle of measurement, construction of transmitter coil assembly, and simple but accurate direct calibration are also described. PMID- 1934913 TI - A computer controlled scanner for the laser treatment of vascular lesions and hyperpigmentation. AB - A computer controlled scanner has been used with a copper vapour laser for the treatment of vascular lesions and hyperpigmented lesions. The computer controls the position and speed of travel of the laser spot during treatment. The illumination time is adjustable with a minimum of 1 ms. The light from the laser is scanned over the lesion so that the lesion is 'painted in' in a raster-like scan of arbitrary shape and produces a series of parallel lines 0.6 mm apart. PMID- 1934914 TI - Simultaneous determination of glomerular filtration rate and effective renal plasma flow. AB - A method is described for the simultaneous determination of GFR and ERPF within the normal range using a single injection of 51Cr-EDTA and 125I-OIH. Reference values of GFR (range 59-176 ml min-1) and ERPF (268-810 ml min-1) were calculated from bi-exponential analysis of curves based on multiple plasma samples. A subset of the samples (44, 120, 180 and 240 min) was used to estimate GFR by fitting a bi-exponential curve. Regression analysis demonstrated that the reference GFR value could be predicted from this four-sample estimate with a standard error of estimate (SEE) of 2.9 ml min-1, which compared favourably with methods based on mono-exponential analysis (minimum SEE = 6.3 ml min-1) or single samples (minimum SEE = 7.7 ml min-1). The effective volume of distribution of 125I-OIH calculated from the 44 min sample was used to estimate ERPF using a published equation with a SEE of 52 ml min-1. The improved precision of this simplified method for the simultaneous measurement of GFR and ERPF in the normal range will facilitate longitudinal studies in large patient groups in the evaluation of the causative factors of renal disease. PMID- 1934915 TI - A simplified method for measuring cerebral blood flow with xenon-enhanced computed tomography. AB - The measurement of cerebral blood flow using the xenon-enhanced computed tomography (XECT) technique requires that the build-up of xenon in both brain tissue and end-tidal expired air be determined as a function of time. Monitoring of the former is carried out using CT scanning and the latter, most often, using a thermoconductivity analyser or mass spectrometer. This paper examines the possibility of greatly simplifying the XECT technique by eliminating the need for either thermoconductivity analyser or mass spectrometer. In the proposed approach, the patient's expired air is channelled through the scan field using a flexible plastic tube and sampled by the CT scanner in conjunction with the build up of xenon in brain tissue. Phantom measurements have demonstrated the ability of the CT scanner to detect variations in the xenon concentration in expired air while computer simulations have shown that errors arising as a result of the proposed methodology are small compared to other inherent sources in the XECT technique. PMID- 1934916 TI - A mathematical model of some aspects of jet nebuliser performance. AB - A simple mathematical model describing the performance of an Acorn jet nebuliser system (Medic-Aid Ltd) has been developed in which nebuliser efficiency E, defined as the volume fraction of solution (water) released as an aerosol or lost by evaporation, and nebulisation time T, are given as functions of the initial volume of solution. The model identifies an initial phase during which the nebuliser output is at a constant, continuous rate of 0.007 ml s-1. This is followed by an intermittent phase of operation during which output is estimated to occur for 0.25 of the total duration of the phase and results from solution deposited on the walls being recycled. The model indicates that increasing the flow of solution to the nebulisation region in the nebuliser or decreasing the fraction of aerosol intercepted by the baffle, will decrease T whilst leaving E unaffected. Two residence times tau 1, tau 2 which are a measure of the time that solution droplets adhere to the inner walls of the nebuliser are also identified; tau 1 (= 1.6 s) is the residence time associated with the rapid recycling of the majority (a fraction eta 1 = 0.992) of the aerosol while tau 2 (= 200 s) the residence time associated with the remaining fraction 1 - eta 1. Increasing eta 1 will increase E for constant tau 1, tau 2 while increasing tau 1, tau 2 will decrease E, T remaining essentially unchanged. It is proposed that the model may be applicable to other jet nebulisers. PMID- 1934917 TI - Guidelines for Pneumocystis carinii pneumonia prophylaxis in children issued. PMID- 1934918 TI - Drug use during breast-feeding. AB - The physicochemical and pharmacokinetic factors involved in transfer of drugs into breast milk are reviewed. Passage of drugs into milk can best be viewed as a two-compartment system. Various ratios of the drug concentration values in the two compartments and ratios of maternal-to-infant intake have been described. Knowledge of the limitations of these methods is necessary to properly interpret and apply the literature on drug excretion into breast milk. Factors involved in choosing a drug for a nursing mother are listed, a stepwise approach to minimizing transfer of drug to the infant is presented, and the literature on the excretion of specific drugs into milk is reviewed. Generally, drugs given to nursing mothers reach infants in much smaller amounts than drugs given to pregnant women. Decisions about nursing during drug therapy and the choice of drug therapy in a nursing mother should be based on the dosage and duration of therapy, age of the infant, quantity of milk consumed, experience with the drug in infants, degree of oral absorption of the drug by the infant, potential long term effects, possible interference with lactation, and non-dose-related toxicities (e.g., potential allergic reactions). Too often, the mother's need for a medication is perceived as a reason to discontinue nursing. By understanding the principles of drug passage into breast milk and systematically evaluating the mother's needs, infant factors, and the data on specific drugs, clinicians can usually devise treatment plans that allow nursing while minimizing the risks to the infant. PMID- 1934919 TI - Determination of sedative and amnestic doses of lorazepam in children. AB - An open-label, dose-escalation study was conducted to determine doses of lorazepam required to induce anterograde amnesia and sedation in children without producing excessive toxicity. Oncology patients 4 to 17 years of age undergoing lumbar puncture or bone marrow aspiration were eligible; a patient could be entered in the study for a second procedure at a different lorazepam dose. A single oral dose of lorazepam was administered 45-60 minutes before the procedure. Starting with 0.02 mg/kg, the same dose was given to three patients; if no dose-limiting effects occurred, dose was increased by 0.01 mg/kg. Before the procedure the patient was shown a toy that he or she was later asked to identify. Immediately after the procedure (usually 60-75 minutes after the lorazepam dose), sedation was assessed on a scale of 0 (alert) to 4 (coma), and the clinician performing the procedure was asked to subjectively evaluate sedation. Patients were rated for amnesia 24 hours after the procedure; a scale of 0 (recalls procedure and toy without prompting) to 4 (recalls nothing since procedure) was used. Twenty patients received 28 doses of lorazepam. The study was terminated when two patients who received 0.10 mg/kg had excessive ataxia. Sedation was subjectively considered adequate for 24 of the procedures. Sedation and amnesia scores were not well correlated with increased dose. Amnesia occurred in some patients with doses as low as 0.03 mg/kg. In children undergoing lumbar puncture or bone marrow aspiration, premedication with oral lorazepam 0.02-0.09 mg/kg generally produced adequate sedation for the procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1934920 TI - Infusion failure caused by phlebitis and extravasation. PMID- 1934921 TI - Blood product support in patients undergoing chemotherapy and autologous or allogeneic bone marrow transplantation for haematological malignancies. AB - Three groups of patients with leukaemia and myelodysplasia were assessed with regard to the blood product support they required during their period of bone marrow hypoplasia following treatment. One group received myelo-ablative remission-induction chemotherapy followed by appropriate consolidation therapy (two courses in patients with acute myeloid leukaemia and one or two intensification courses in patients with acute lymphoblastic leukaemia); whilst the other two had 'conditioning' with chemotherapy and radiotherapy prior to autologous bone marrow transplantation (auto-BMT) or T cell depleted allogeneic bone marrow transplantation (allo-BMT). There was no statistically significant difference in blood product requirements between the three groups. However, platelet requirements during remission-induction chemotherapy alone were significantly less than for allo-BMT or auto-BMT. Platelet requirements for patients undergoing auto-BMT were also significantly higher than for patients receiving consolidation chemotherapy; and were required for a longer period than for patients receiving allogeneic-BMT. There was no difference in blood product support between ABO matched and mismatched transplants within the allogeneic group, but the presence of graft versus host disease and/or cytomegalovirus infection did significantly increase the requirements for blood product support. PMID- 1934922 TI - Prognostic indicators for the development of AIDS in HIV antibody positive haemophiliac patients: results of a three-year longitudinal study. AB - In February 1986, 40 out of 75 adult patients with haemophilia A attending St. James's University Hospital were human immunodeficiency virus (HIV) antibody positive. Over a three-year period these patients were prospectively studied with regard to possible prognostic indicators for the development of the acquired immune deficiency syndrome (AIDS). Using the Centres for Disease Control (CDC) classification of HIV infection, 17 patients (42.5%) developed group 4 disease during this time, giving an actuarial three-year progression rate of 44%, and 5 patients (12.5%) died. The following parameters measured at recruitment were found independently to predict progression to AIDS: a serum beta 2-m level of greater than 3.5 mg/l, (chi 2 = 15.95, P less than 0.001), a serum IgA level of greater than 4.5 milligram(s) (chi 2 = 6.08, P less than 0.02) and p24 antigenaemia (chi 2 = 5.7, P less than 0.05). The actuarial three-year progression rate in those patients abnormal by two or more of these parameters was 100% (n = 7), compared to only 7% in patients who were normal by all three values (n = 15). CD4+ lymphocyte counts and CD4+:CD8+ ratios were significantly lower in HIV positive compared with HIV negative patients (P less than 0.01), but did not predict the development of AIDS. PMID- 1934923 TI - Inter-relationships between platelet count, platelet IgG, serum IgG, immune complexes and severity of liver disease. AB - Thrombocytopenia is a common finding in subjects with chronic liver diseases. A variety of mechanisms may underlie this. Immunological disturbances are commonly a feature in chronic liver disease, including hyperglobulinaemia and the presence of autoantibodies and circulating immune complexes and immune mechanisms could therefore contribute to thrombocytopenia. We have investigated the relationships between blood platelet count, serum IgG and IgG immune complexes and IgG associated with platelets in 92 subjects with chronic liver disease (27 with chronic active hepatitis, 38 with primary biliary cirrhosis and 27 with alcoholic liver disease). Severity of liver impairment was a major determinant of degree of thrombocytopenia. Also, an inverse relationship was demonstrated between platelet count and platelet-associated IgG. In subjects with chronic active hepatitis the relationships between platelet count, serum IgG immune complexes and platelet associated IgG were consistent with a role for immune mechanisms in general and immune complexes in particular as mediators of the thrombocytopenia. PMID- 1934924 TI - Mesenteric venous thrombosis due to protein C deficiency. AB - Protein C deficiency is a known underlying risk factor for thromboembolic disease. Most commonly it presents as thrombophlebitis, deep venous thrombosis or pulmonary embolism. Less common presentations are becoming increasingly recognized now that assays for protein C are more widely available. We present two cases of mesenteric venous thrombosis who were found to have protein C deficiency. PMID- 1934925 TI - Relevance of red cell distribution width (RDW) in the differential diagnosis of microcytic anaemias. AB - The authors studied the red cell distribution width (RDW) index (obtained by Coulter Counter S Plus IV) in normal subjects and in patients with beta thalassaemia trait and iron deficiency anaemia. Statistics and reference limits for the above three conditions are given. In order to make a differential diagnosis between beta-thalassaemia trait and iron deficiency anaemia, linear discriminant analysis was carried out. Global correct classification was 91.5% on our first sample of patients and 88.8% on a subsequent validation sample of microcytic patients. The percent of correct beta-thalassaemia trait diagnoses was 94.4% and 86.7% for the first and validation samples respectively. For iron deficiency anaemia correct diagnoses of 86.2% and 90.9% were achieved. PMID- 1934926 TI - A study of changes in red cell volume and haemoglobin concentration during phlebotomy induced iron deficiency and iron repletion using the Technicon H1. AB - The recently introduced Technicon H1 analyser uses an improved optical principle to measure the size and haemoglobin concentration of erythrocytes. We have made a serial study of ten patients undergoing phlebotomy to induce mild iron deficiency. The instrument showed the early development of anisohypochromia with subsequent fall in the mean cell haemoglobin concentration (MCHC). Cell volume was preserved until relatively late and during early iron deficient erythropoiesis cell volume would appear to be maintained at the expense of haemoglobin concentration. The Technicon H6000 (conventional technology) used in parallel produced contrasting results indicating anisomicrocytosis with preservation of cell haemoglobin concentration until relatively late. Five cases of severe iron deficiency treated with iron were similarly studied and showed comparable changes on both instruments, with characteristically bimodal cell volume histograms and large increases in red cell distribution width. Our results indicate that the new generation of instruments will generate red cell data of additional clinical value. PMID- 1934927 TI - Bone marrow necrosis complicating chronic myeloid leukaemia. AB - Two women with chronic myeloid leukaemia in chronic phase were found to have bone marrow necrosis when severe bone pains and falling blood counts prompted a marrow examination to exclude blast transformation. One patient survived for 12 months following the event without transforming. The second patient died soon after and was found to have widespread extramedullary disease. PMID- 1934928 TI - Storage and preparation of samples for erythropoietin radioimmunoassay. AB - The evaluation of a radioimmunoassay for erythropoietin developed using recombinant material as immunogen and radiotracer is presented. A series of serum samples prepared and stored under varying conditions showed that immunoreactive erythropoietin levels were stable at room temperature for at least 10 days and at -20 degrees C for 5 months. The optimum time for separating sera from samples was between 6 and 24 h after venepuncture. Serum EPO values were significantly higher than those measured in heparin or potassium EDTA plasma. PMID- 1934929 TI - Quick cytochemical staining of blood and bone marrow cells in a microwave oven. PMID- 1934930 TI - Therapy-related leukaemia in Wegener's granulomatosis. PMID- 1934932 TI - Retinal detachments due to chronic lymphocytic leukaemia. PMID- 1934931 TI - Eosinophilic leukaemia with an abnormality of 5q31, the site of the IL-5 gene. PMID- 1934933 TI - Discrepant INR values strike again. PMID- 1934934 TI - The correlation between red cell distribution width and serum erythropoietin titres. PMID- 1934935 TI - Red cell aplasia in mother and son. PMID- 1934936 TI - Involvement of feedforward stimulation in cardiorespiratory and metabolic control during exercise. PMID- 1934937 TI - Blood volume distribution during head-up tilt induced central hypovolaemia in man. AB - We evaluated regional electrical impedance (Z degree) at 2.5 and 100 kHz to separate intra- and extracellular fluid changes and correlated Z degree over the thorax (TI) to relative changes in the central blood volume (CBV) induced by head up tilt. In nine experiments head-up tilt resulted in normotensive central hypovolaemia associated with a 3.7 +/- 0.4 Ohm (mean +/- SE) increase in TI100 kHz after 60 min. In 24 experiments pre-syncopal symptoms were induced after 43 +/- 2 min, when TI100 kHz had increased 4.2 +/- 0.2 Ohm. Head-up tilt instantly decreased the activity of technetium labelled erythrocytes (99Tcm) over the thorax by 24 +/- 2%, and increased 99Tcm over the thigh by 68 +/- 10% (P less than 0.01, n = 8) with no further changes during the sustained tilt. Haematocrite increased during head-up tilt from 43.1 +/- 0.3 to 47.9 +/- 0.6% (P less than 0.01, n = 8). Accordingly, the increase in TI (6.3 +/- 0.6 vs. 4.5 +/- 0.4 Ohm, n = 6) and the decrease in Z degree through one leg (7.2 +/- 1.2 vs. 2.8 +/- 0.5 Ohm, n = 6) at 2.5 kHz was more pronounced than at 100 kHz. Also the changes in TI were correlated to CBV as calculated from 99Tcm and haematocrite (r = 0.90, P less than 0.01). The results suggest that: (1) Hypovolaemic shock is associated with a faster increase of TI than normotensive head-up tilt. (2) Head-up tilt is characterized by an initial decrease in CBV followed by a further decrease in plasma volume, which eventually leads to hypovolaemic shock. (3) Blood volume changes during head-up tilt are reflected in regional Z degree. PMID- 1934938 TI - QRS scoring with the Mason-Likar lead system at rest and during ischaemia. AB - The stability of the post-infarction simplified 29-point Selvester QRS score during maximal exercise testing was studied using both standard 12 and Mason Likar (modified standard, M-L) ECG lead systems. Thirty-eight patients participated in the standard exercise test (mean interval after single infarction 4 months) and a total of 54 patients underwent exercise 201thallium emission tomography with M-L lead system 2 months later. None had electrocardiographic features complicating the scoring. There were no significant differences between the (paired) mean QRS scores, except between the M-L score at rest (2.3 +/- 2.4) and at exercise (3.2 +/- 2.6, P less than 0.01). The correlation coefficient (r) between resting scores was 0.87, between rest and exercise 0.90 (standard leads) and 0.80 (M-L leads). In 78% nuclear imaging revealed ischaemia, but this had no significant effect on the mean scores or correlation between rest and exercise scores. It is concluded that the QRS score is relatively stable during exercise with standard leads if the limb leads are recorded immediately after the exercise. Scoring with the M-L lead system is somewhat inaccurate, especially during exercise, and is not recommended for stratification of clinical risk. The QRS score is protected against ischaemia, which emphasizes its value as an independent prognostic tool. PMID- 1934939 TI - Recoveries of phosphatidylcholine and alveolar macrophages in lung lavage from healthy light smokers. AB - Twenty-one healthy volunteers, 11 light smokers and 10 non-smokers, were studied by broncho-alveolar lavage. The levels of the phosphatidylcholine (PC) in broncho alveolar lavage were measured and used as an index of surfactant. The PC levels in broncho-alveolar lavage obtained from the smokers were significantly lower than in lavage fluid from the non-smokers. There was an inverse correlation between PC levels and cumulated tobacco smoke exposure, as estimated by the number of pack-years, and to current smoking habits as estimated by the number of cigarettes smoked per day. The number of alveolar macrophages was significantly higher in broncho-alveolar lavage obtained from smokers, and there was a significant inverse correlation between PC levels and numbers of alveolar macrophages in the lavage fluids. The potential role of alveolar macrophages in the elimination of surfactant lipids is discussed. PMID- 1934940 TI - The effect of forced expirations on mucociliary clearance in patients with chronic bronchitis and in healthy subjects. AB - Animal studies have shown that frequent coughing may damage the mucociliary apparatus in flow-limiting segments of the central airways. To determine whether mucociliary clearance in humans is affected by repeated dynamic compression associated with forced expirations, we measured pulmonary deposition and mucociliary clearance for 2 h of inhaled [99Tcm]albumin. The subjects inhaled [99Tcm]albumin on 2 study days (randomized) using (A) slow inspirations and forced expirations, while inhalation using (B) forced inspirations and slow expirations served as control. The study was conducted using 10 patients with chronic hypersecretory/obstructive bronchitis and six normal subjects. We found that inhalation of [99Tcm]albumin by the two manoeuvres (A and B) resulted in similar patterns of aerosol deposition. There was no significant difference in retention of radioactivity in the central lung region at 1 h in the patients with chronic bronchitis after inhalation with manoeuvre A (102%) and with manoeuvre B (91.5%), or in the healthy subjects after manoeuvre A (74%) and manoeuvre B (77%). There was also no difference in the retention at 2 h or in overall mucociliary clearance in any of the groups. We conclude that dynamic compression in the central airways associated with forced expiration does not affect bronchial clearance in the airways of healthy subjects or in patients with chronic bronchitis. PMID- 1934941 TI - Local and central sympathetic reflex control of blood flow in skeletal muscle and subcutaneous tissue in normal man. AB - The effect of age and sex on relative changes in blood flow and vascular resistance in skeletal muscle and subcutaneous tissue during postural changes and during local increase in transmural pressure was studied in 33 healthy subjects. The intra-individual variation was studied in five subjects. Blood flow was measured by the local 133Xenon wash-out method. No relation to age or sex was seen in the centrally elicited sympathetic vasoconstrictor responses in subcutaneous tissue and skeletal muscle and in the locally elicited vasoconstriction in subcutaneous tissue. A small, but statistically significant, correlation to sex and age was found in the local sympathetic vasoconstrictor response in skeletal muscle. The age correlation was caused only by an attenuated response in the young subjects below 40 years of age and may be fortuitous. The intra-individual variation was acceptably small. Based on the present results, a reduction in blood flow in skeletal muscle and subcutaneous tissue during centrally or locally elicited sympathetic vasoconstriction of 10% or less should be considered abnormal. The local 133Xenon wash-out method is of value in examining patients suspected of dysfunction in the sympathetic part of the autonomic nervous system. PMID- 1934942 TI - Metabolism in exercising arm vs. leg muscle. AB - Arm and leg metabolism were compared by arterial and venous catheterization and blood flow measurements (by dye dilution techniques) in two groups of subjects performing 30-min continuous arm or leg exercise of increasing intensity corresponding to approximately 30, 50 and 80% of max oxygen uptake for arm or leg exercise. The absolute work-loads were 2.5-3 times higher during leg compared to arm exercise. Heart rates were the same in both types of exercise. r-Values were 0.97-1.07 during arm exercise. Arterial noradrenaline and adrenaline levels became higher during leg compared to arm exercise (P less than 0.05-0.01). Arterial lactate concentration was 50% higher for arm exercise at the two lower intensities (P less than 0.001) and the same at the highest intensity compared to leg exercise. Arm lactate release was three times higher (P less than 0.01) or the same as leg lactate output at corresponding exercise intensities. Arm and leg glucose uptake during exercise were of the same magnitude at the lower intensities. In contrast to the leg substrate exchange, arm lactate output was higher than the simultaneous glucose uptake (P less than 0.05-0.001), indicating a relatively higher rate of glycogen degradation. In conclusion, exercising arm compared to leg muscles working at the same relative intensities utilize more carbohydrate, mainly muscle glycogen resulting in higher lactate release by the exercising extremity. This cannot solely be explained on the basis of differences in the degree of training and occurs with lower catecholamine levels compared to leg exercise. PMID- 1934943 TI - Arterial and venous measurement in resting forearm of metabolic indicators during rest and leg exercise. AB - We compared the levels of various metabolic indicators in arterial and venous forearm blood during maximal treadmill leg exercise, and the subsequent 9 min in nine volunteers aged 31-56 years. At maximal exercise plasma lactate was 13.2 +/- 3.1 mmol l-1 arterially, while venous was 41% lower, but increased more than arterial after exercise. There was a linear relationship between arterial and venous samples during and after exercise, but not at baseline. Plasma pyruvate increased on the arterial side from 49 +/- 8 to 172 +/- 30 mumol l-1 at maximal exercise, maximal venous was 21% lower. Free fatty acids were not different at rest, but decreased during exercise by 52 and 38% on the arterial and venous side. There was no relationship between arterial and venous levels. Changes in these three variables occurred significantly earlier on the arterial side. Arterial cyclic AMP rose from 97.3 +/- 28.4 to 262.7 +/- 67.5 nmol l-1 from rest to exercise, and was linearly inversely related to the decrease in free fatty acids. The mean venous pH was lower than arterial at rest, but was the same as arterial at maximal exercise and after. Thus, venous plasma lactate and pyruvate, but not free fatty acids, are linearly related to arterial measurements during maximal exercise, while pH is identical. Non-working muscle modifies exercise induced changes, and therefore venous and arterial forearm blood sampling give more information than either alone. PMID- 1934944 TI - Adenosine infusion to patients with ischaemic heart disease may provoke left ventricular dysfunction detected by echocardiography. AB - Infusion of the endogenous vasodilator adenosine to patients with ischaemic heart disease (IHD) frequently provokes myocardial ischaemia, possibly caused by a coronary steal. The aim of this study was to detect the occurrence and incidence of disturbances in left ventricular (LV) wall motion and Doppler indices of altered LV function during infusion of adenosine. Thirty-seven patients (six female) aged 37-74 years with IHD, verified by coronary angiography, were given up to 200 micrograms kg-1 min-1 (mean 155 +/- 5) adenosine i.v. for 18 +/- 1 min. LV wall motion was monitored by two-dimensional echocardiography (2D-echo). Doppler spectral signal was obtained from the mitral blood flow. All but six of the patients experienced angina pectoris of habitual character in connection with the adenosine infusion. Heart rate increased by 22 +/- 1 beats min-1, systolic blood pressure was unchanged, but diastolic blood pressure decreased slightly. 2D echo revealed severe regional LV wall motion disturbances already in the basal state in 17 patients. During infusion of adenosine, these abnormalities were aggravated and disturbances also occurred in another 15 patients. Thus, adenosine increased the sensitivity for IHD in this selected material from 49 to 89%. In all, the mean index of wall motion abnormalities increased from 5.1 +/- 1.1 to 10.1 +/- 1.4 (P less than 0.001). The diastolic LV filling characteristics, as evaluated by the Doppler A/E ratios, were of limited value for determination of IHD grade. It is concluded that infusion of adenosine to patients with IHD frequently elicits myocardial ischaemia with disturbances in LV function, and offers an alternative to exercise for stress echocardiography. PMID- 1934945 TI - Laryngeal anatomy and physiology. AB - Much has been learned about the normal function of the larynx. As is perhaps obvious from our article, much, much more needs to be learned about its function in altered and disease states. PMID- 1934946 TI - Airway management in the critically ill patient. PMID- 1934947 TI - Physiologic consequences of tracheal intubation. AB - Many principles that originate in the operating room and in fluid mechanics modeling are relevant to endotracheal intubation in the pulmonary and critical care setting. These factors should be appreciated by pulmonologists and intensivists, as they may contribute to improved safety during the process of airway access. The usual reflex responses to stimulation of oropharyngeal and upper airway receptors include glottic closure, hypertension, tachycardia, and reflex bronchoconstriction. These reflexes can be modified by technical or pharmacologic reduction of sensory receptor stimulation or by parenteral agents, which diminish efferent responses, including anesthetics, vasoactive drugs, and adrenergic blockers. Topical anesthesia and parenteral sedatives may be the preferred agents when overall risk and benefit are considered. Intubation also has consequences related to a reduction in airway caliber, to changes in respiratory mechanics, and to the creation of turbulent airflow in the endotracheal tube. PMID- 1934948 TI - Technical standards for tracheal tubes. AB - To provide an appropriate context for understanding the standards for tracheal tubes, this article first summarizes some of the historical highlights leading to the development of present-day tracheal tubes. It also describes the current manufacturing guidelines for tracheal tubes and the rationale for these standards. PMID- 1934949 TI - Medical management of the airway. AB - All critical care physicians should be adept at medical management of the airway, including basic and advanced life support measures. Proper head and neck positioning, use of non-definitive airways, and ability to oxygenate and ventilate the patient with bag-valve-mask should be part of the armamentarium of every critical care physician. Training, skill, and experience are fundamental to successful translaryngeal intubation. The nasal and oral routes of such intubation each have distinct advantages and disadvantages. Oral intubation is preferred for emergency establishment of a definitive airway in most situations. Skillful intubation technique and meticulous daily management of the upper airway should diminish the risk of complications of translaryngeal intubation. PMID- 1934950 TI - Management of the difficult airway. AB - For clinicians involved in airway management, a plan of action for dealing with the difficult airway or a failed intubation should be developed well in advance of encountering a patient in whom intubation is not routine. When difficulty is anticipated, the equipment necessary for performing a difficult intubation should be immediately available. It also is prudent to have a surgeon skilled in performing a tracheotomy and a criothyroidotomy stand by. The intubation should be attempted in the awake state, preferably using the fiberoptic bronchoscope. The more challenging situation is when the difficult airway is confronted unexpectedly. After the first failed attempt at laryngoscopy, head position should be checked and the patient ventilated with oxygen by mask. A smaller styletted tube and possibly a different laryngoscope blade should be selected for a second attempt at intubation. The fiberoptic bronchoscope and other equipment for difficult intubation should be obtained. A second attempt should then be made. If this is unsuccessful, the patient should be reoxygenated, and assistance including a skilled anesthesiologist and surgeon should be summoned. On a third attempt, traction to the tongue can be applied by an assistant, a tube changer could be used to enter the larynx, or one of the other special techniques previously described can be used. If this third attempt fails, it may be helpful to have a physician more experienced in airway management attempt intubation after oxygen has been administered to the patient. If all attempts are unsuccessful, then invasive techniques to secure the airway will have to be performed. PMID- 1934951 TI - Double-lumen endotracheal tubes. AB - Double-lumen endotracheal tubes have revolutionized the anesthetic management of patients undergoing thoracic surgery. As experience with the techniques of DLT placement and monitoring progress, an increasing number of uses in the intensive care unit will evolve. Benefit from differential lung ventilation in patients with respiratory failure from unilateral lung diseases and bronchopleural fistulae has been documented in selected instances. Isolation of the lungs to prevent contralateral spread of hemoptysis is occasionally of assistance. Frequent monitoring of DLT position while understanding the physiology of differential lung ventilation will minimize complications with these tubes. PMID- 1934952 TI - Complications of translaryngeal intubation. AB - The human larynx is complex and serves multiple functions. Unfortunately, endotracheal tubes do not reproduce all these functions. They serve well as air passages but cannot do so without damaging the mucosa of the posterior larynx. It appears that complications secondary to airway problems in the operating room are decreasing as the use of oximetry and capnometry becomes routine. It is hoped that this reduction in complications will carry over into the chronic care setting as such monitoring becomes the standard after intubations. Compared with malposition of the tube, most of the other complications of intubation are minor. However, knowledge of the various complications can ensure avoidance of many and early detection and correction of others. PMID- 1934953 TI - The impact of tracheal intubation on host defenses and risks for nosocomial pneumonia. AB - Nosocomial pneumonia remains a common complication in patients treated with endotracheal intubation and mechanical ventilation and continues to have a significant impact on the mortality rate of these patients. Epidemiologic studies have shown that the risk of pneumonia increases with the duration of intubation but that the period of highest risk is the first 2 weeks of therapy. Gram negative bacteria account for most nosocomial pneumonias in intubated patients, but Staphylococcus aureus may also play a role in what may be a polymicrobial infection. In the most seriously ill individuals, and in those treated with long term mechanical ventilation, Pseudomonas aeruginosa is a common pathogen. Endotracheal intubation and mechanical ventilation predispose to pneumonia for a variety of reasons (see Fig. 1). The endotracheal tube can have direct effects on the airway that result in a reduction in local host defenses. Thus, mucosal injury can reduce mucociliary function, while upper airway defenses are bypassed and the effectiveness of cough is reduced. Indirectly, intubation can result in an enhanced capacity of tracheobronchial cells to bind gram-negative bacteria, an effect that favors airway colonization and pneumonia. The injury to the airway can create binding sites for bacteria in the basement membrane of the bronchial tree and the stimulation of the secretion of mucus, which then stagnates and can create potential sites for bacterial adherence. The endotracheal tube also enhances bacterial entry to the lung by serving as a reservoir for bacteria to remain sequestered, safe from host defenses. Respiratory therapy devices can allow bacteria to proliferate and can then introduce them into the patient if not handled properly. Finally, patients who are ill enough to require intubation also have disease-associated impairments in systemic host defense, which add to the impairments caused by the use of an artificial airway. The host defense impairments that occur in mechanically ventilated patients can lead to respiratory tract infection in the form of either febrile tracheobronchitis or pneumonia. The diagnosis of pneumonia in intubated patients is difficult and controversial. It can be made by either clinical criteria or microbiologic criteria, the latter by using a bronchoscopically directed protected specimen brush. Therapy of pneumonia in mechanically ventilated patients is not always successful, and systemic antibiotics may need to be supplemented by topical antimicrobials. No clearly effective prophylactic strategy currently exists, but our understanding of pneumonia pathogenesis has led to some promising directions. As more data are collected, inhaled antibiotics, selective digestive decontamination, and enhancement of host defenses by cytokines and pre-formed antibodies may emerge as useful approaches. PMID- 1934954 TI - Indications for and techniques of tracheotomy. AB - Although the operation has been practiced for centuries, the modern technique of tracheotomy was introduced and popularized in the beginning of the 20th century. The initial indication for tracheotomy was limited to impending airway obstruction resulting from trauma, but current indications are broader. Tracheotomy is one of four methods available to intubate the trachea and is associated with physiologic changes that are dependent on the duration of tracheotomy. Although surgical in nature, it is employed to relieve or prevent airway obstruction and to offer ventilatory support. Tracheotomy may be performed as an elective or an emergency procedure. Ideally, it is done in a controlled situation. However, when performed in an emergency setting, variations of the procedure, such as minitracheotomy or cricothyroidotomy, may be temporarily substituted. Preferably, tracheotomy is performed in an operating room; however, it may be carried out successfully in an intensive care unit as well. PMID- 1934955 TI - Elective tracheotomy for mechanical ventilation by the percutaneous technique. AB - Percutaneous dilatational tracheotomy is a safe, efficient procedure for elective tracheostomy placement. It is not a technique for emergency tracheotomy. It should be performed only by surgeons experienced in conventional tracheotomy. The advantages of placement at the bedside, speed, and relative inexpense make it attractive in the care of critically ill patients. PMID- 1934956 TI - The role of cricothyroidotomy in airway management. AB - Cricothyroidotomy as a method of elective airway management, previously shunned by Jackson, was reintroduced to the medical community in 1976. This article examines available data indicating the utility and complications of elective cricothyroidotomy for long-term airway management and defines its place with respect to tracheotomy. PMID- 1934957 TI - Special critical care considerations in tracheostomy management. AB - The tracheotomized patient undergoing mechanical ventilation presents numerous challenges to the intensive care team. During the initial phase of respiratory failure, patient instability and risks of multiorgan failure focus efforts on an array of critical care management techniques designed to reverse the underlying process and prevent complications. During the stabilization phase, issues of tracheostomy care become equally important in improving patient outcome. These topics include the proper assistance in patient communication, initiation of enteral nutrition, weaning from airway cannulation, and anticipation of adverse reactions after airway decannulation. Failure in promoting a logically conceived and carefully applied treatment plan in any of these areas frequently delays patient recovery and risks serious complications of airway compromise. PMID- 1934958 TI - Airway management in obesity hypoventilation syndrome. AB - The role of tracheostomy is limited in the obesity hypoventilation syndrome unless severe upper airway obstruction exists. If it is performed, special techniques must be applied to overcome the problems associated with tracheostomy in the morbidly obese patient. If attention is paid to these details, however, tracheostomy provides clinically important benefits in this difficult clinical situation. PMID- 1934959 TI - Early complications of tracheotomy. Incidence and management. AB - Tracheotomy is associated with multiple and potentially life-threatening complications even under elective conditions. Minor bleeding, tube displacement or obstruction, subcutaneous emphysema, and pneumothorax are the most commonly encountered complications. Attention to details and the availability of adequate instrumentation, lighting, and trained personnel are essential to minimize morbidity. PMID- 1934960 TI - Late complications of tracheotomy. AB - Complications of tracheotomy are largely preventable. Although some authors cite these complications as indications for prolonged endotracheal intubation to avoid tracheotomy, others believe that the laryngotracheal complications of prolonged endotracheal intubation warrant early tracheotomy. Obviously, unnecessary tracheotomies should not be performed, and the controversy regarding the timing of conversion of endotracheal intubation to tracheotomy is handled in an earlier article in this issue. We feel, however, that a properly performed tracheotomy has a low incidence of complications that are more easily managed than are the complex laryngotracheal complications of prolonged endotracheal intubation. Significant post-tracheotomy tracheal stenosis occurs in 8% of patients and is secondary to an overly large tracheotomy stoma or damage at the tracheostomy tube cuff site. Stoma stenosis can be minimized by not making an overly large tracheal stoma and by prevention of undue leverage on the tracheostomy tube. Cuff stenosis can be minimized by the use of the high-volume low-pressure cuffs with careful prevention of overdistention of the cuff. Bronchoscopic dilatation, laser resection, and Silastic T-tube placement provide control of the airway until definitive surgical resection and reconstruction can be performed safely. Tracheoesophageal fistula is an uncommon but life-threatening complication that can be prevented by avoiding overdistention of the tracheostomy tube cuff and by avoiding the concomitant use of a stiff nasogastric tube. These patients are best managed conservatively until they are able to be weaned from a ventilator. A single-stage repair of both the esophagus and the trachea should then be done. Tracheoinnominate artery fistula can be avoided by correct placement of the tracheostomy stoma through the second and third tracheal rings rather than lower in the trachea and by avoidance of overinflation of tracheostomy tube cuffs. PMID- 1934961 TI - Timing of tracheotomy in ventilator-dependent patients. AB - During the last 20 years, improved critical care techniques have enhanced the probability that the condition of patients with respiratory failure will stabilize sufficiently to allow long-term mechanical ventilation. Patients undergoing the transition to prolonged ventilatory support benefit from a timely application of tracheotomy guided by a clear understanding of its risk and benefits. Although numerous investigations since 1970 compare patient outcome from tracheotomy with that after prolonged translaryngeal intubation, limitations of study design and varying results among institutions prevent absolute recommendations for timing tracheotomy. A critical review of the available data, however, allows individualization of care and an anticipatory approach to institution of the surgical airway. PMID- 1934962 TI - Immunogenetics of the human major histocompatibility complex. AB - The biologic significance of the human major histocompatibility complex (MHC), also referred to as HLA, is well known through its influence on transplant immunity and its association with many diseases. This article attempts to summarize recent progress in the field of HLA polymorphisms. Topics discussed include the genetic basis of HLA, methods to determine HLA polymorphisms, and definitions of HLA Class I and II polymorphisms. PMID- 1934963 TI - Laboratory testing in organ transplantation. Laboratory management: Regulation of clinical laboratories. PMID- 1934964 TI - The influence of HLA and ABO antigens on graft rejection and survival. AB - The major histocompatibility complex (MHC) initially was identified by its strong association with the outcome of transplanted tissues. As in other species, disparity for MHC antigens in humans (especially HLA-A, B, DR) is a good predictor of allograft rejection. Although new immunosuppressive agents have improved graft survival in clinical transplantation, they have not obviated the benefits of avoiding mismatched HLA antigens or incompatible ABO blood group antigens. This article examines the role of HLA and ABO antigens in graft rejection from the perspective of both immunologic mechanisms and clinical outcome. PMID- 1934965 TI - Donor-specific antibodies. Clinical relevance of antibodies detected in lymphocyte crossmatches. AB - Positive donor crossmatches due to lymphocytotoxic antibodies generally have an adverse effect on allograft survival, but with numerous variations. Different laboratory techniques used to characterize lymphocytotoxic antibody, new antibody systems, such as those incited by endothelial/monocyte and epithelial antigens, the variable tempos and histopathologic changes of early rejections caused by these antibodies, and the specific features imposed by each organ, all combine to make the once simple crossmatch test a complex, clinical and laboratory crossroads, that directs the initial and perhaps ultimate course of the allograft. An integrated assessment of these factors is provided in this article. PMID- 1934966 TI - Crossmatch procedures used in organ transplantation. AB - Several lymphocyte crossmatch procedures used in clinical histocompatibility laboratories, including complement dependent (CDC, AHG-CDC) and complement independent (flow cytometric, chromium release) techniques, are used to assess the likelihood of allograft rejection due to preformed donor specific antibody. Crossmatch assays can be extremely sensitive and detect very low levels of donor reactive antibody present in the potential recipient. Since positive crossmatches are usually associated with allograft rejection, a positive crossmatch is generally a contraindication to organ transplantation. Recent data, however, suggests that not all positive crossmatches lead to graft rejection, particularly those due to autoantibodies. This underscores the need to critically evaluate any positive crossmatch to determine if the antibodies involved in the reaction are relevant to allograft rejection. PMID- 1934967 TI - Clinical relevance of antibodies to non-HLA antigens in organ transplantation. AB - This article summarizes work that focuses on alloantibodies that bind to endothelial cells and attempts to provide an evaluation of the apparent role that antigens distinct from classic HLA alleles, and not expressed in lymphocytes, may play in kidney transplant rejection. The most recent experience with the donor skin crossmatch in prediction of early kidney allograft rejection also is described. PMID- 1934968 TI - Anti-idiotypic-like antibodies detected following alloimmunization. Their characterization and relevance to allograft acceptance. AB - Anti-idiotypic-like antibodies (Ab2) develop during the course of HLA alloimmunization. Several reports indicate that their presence in alloimmunized patients is associated with superior allograft survival, and their appearance correlates inversely with specific HLA antibodies. These features suggest that the induced auto-Ab2 may interact with regulatory idiotypes of HLA-specific antibodies, and may be part of an early immune regulatory mechanism that facilitates the induction of donor-specific immunosuppression. The observations have great potential clinical implications for pretransplant manipulations of the immune response to facilitate donor-specific immunosuppression, and to predict the fate of allografts in previously alloimmunized recipients. Further development and general application of Ab2 testing, however, require better documentation that regulatory immune networks between HLA antibodies and T cells exist, and that improved methods of Ab2 detection that could be used routinely and duplicated in the clinical laboratory, can be developed. PMID- 1934969 TI - Laboratory monitoring of nonrenal allograft rejection. AB - A variety of methods have been proposed to monitor organ allograft rejection using blood, urine, or body fluids. None of these methods, however, have fulfilled the expectations. Biopsy histology has remained a gold standard in the evaluation of in situ events in the graft. Fine needle aspiration biopsy, although invasive, is less traumatic than needle or open biopsy, particularly during the immediate postoperative course when the frequency of acute cellular rejection is the highest. These histologic and cytologic methods should always be used in combination with other methods of clinical diagnostic tests, particularly infection diagnostics. PMID- 1934971 TI - Laboratory monitoring of therapy with OKT3 and other murine monoclonal antibodies. AB - The first monoclonal antibody (MAb) approved by the Food and Drug Administration (FDA) for therapeutic use, OKT3, is now a standard treatment for organ allograft rejection. This article reviews the interpretation of laboratory tests used to manage patients treated with MAb. Emphasis is placed on OKT3, with which the experience is also the greatest, although comparisons with other MAbs in clinical trials is also discussed. PMID- 1934970 TI - Considerations for monitoring cyclosporine in transplant recipients. AB - Cyclosporine (CsA) monitoring has remained controversial since the advent of the use of CsA in organ transplantation in the early 1980s. This article attempts to clarify for the clinical laboratory worker many of the vagaries associated with CsA monitoring by considering choice of sample matrix, the nature of metabolites, the technical specifications of the assay techniques used for therapeutic monitoring of CsA, comparison of results assessed by the various assays, and the pharmacokinetic considerations associated with choice of sampling time. Expectations for the degree of clinical usefulness achievable for CsA levels through further improvement in assay methodologies are also discussed. PMID- 1934972 TI - Immunologic heterogeneity among potential transplant recipients. Prospects for predicting immune responses to allografts with in vitro tests. AB - The ability to accurately predict the response of a specific patient to a specific organ allograft has long been a goal of organ transplantation. The role of histocompatibility antigens in determining the acceptance or rejection of an allograft-recipient combination has been thoroughly investigated, but is being reevaluated as improved immunosuppressive agents become available. Early efforts at immunologic monitoring are reviewed in addition to more recent efforts that focus on the cellular and molecular mediators of immunity. The authors' own experience with lymphokine measurements in clinical transplantation is also reviewed, with emphasis on the role of interleukin-2 (IL-2) and its soluble receptor (IL-2R) in various transplant-associated conditions. The authors conclude that information useful in the management of transplant patients may be derived from serial measurements of IL-2 and IL-2R, but that infections, especially CMV, may not be ruled out with certainty by these measurements alone. The available data suggest that study of additional lymphokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) may be useful in discriminating rejection from infections in transplant patients. PMID- 1934973 TI - Conclusions: the maintenance of allograft acceptance. AB - This article summarizes all of the findings of the authors in this issue who examined various laboratory procedures used to implement and monitor transplantation treatment strategies. Histocompatibility matching, crossmatching, monitoring immunosuppression and rejection, and immunologic monitoring of allograft rejection and acceptance are reviewed. PMID- 1934974 TI - The regulation of medical laboratories in Australia. AB - Australia has had a system of compulsory accreditation and inspection of medical laboratories since 1986. This article details the regulations that have evolved over the years and the specific requirements of this system. The importance of separation of powers of various authorities, including standards, accreditation, payment, inspection, quality assurance, and education, is emphasized. PMID- 1934975 TI - The pathology of regulation. AB - Clinical pathology officially began when inquisitive physicians in the nineteenth century sought explanations for the diseases they observed in their patients. The increasing application of the basic sciences to patients required physicians to spend more time and energy in the laboratory than with their patients. Methodology followed new technologic innovations that the profession began to critically review in the late 1940s. Initially, government involvement in laboratories was minimal and supportive. The role of the government evolved over the last decades from a patron of learning to a purchaser of a regulated commodity and paralleled the changing role of the clinical laboratory from medical practice to big business. PMID- 1934977 TI - Understanding the mind as an active information processor: do young children have a "copy theory of mind"? AB - Most 4-, but no 3-year-olds, were able to understand the mind's active role in evaluating the truth of verbal information. They appreciated that a statement, whether true or false, will be disbelieved if the listener has existing beliefs to the contrary and that it will be believed if no such beliefs exist. Four- and 5-year-olds were equally competent in understanding the need for interpretation of pictorial material. They realized that an uninitiated person cannot make sense of a "droodle", which in itself is an uninterpretable section of a larger meaningful drawing. We discuss the impact of our findings on the question of whether children at this age entertain a copy theory of mind. PMID- 1934976 TI - Familial aggregation of a developmental language disorder. AB - This paper investigates the etiology of developmental dysphasia and its linguistic properties. Data are presented that suggest that at least some cases of dysphasia are associated with an abnormality in a single dominant gene. The results of a series of tests on a large three-generation family, in which half of the members have dysphasia, are reported. These results show that abstract morphology is impaired in these subjects. It is argued further that the data are consistent with the hypothesis that the dysphasics learn the feature-marked lexical items of language as unanalyzed lexical items. They do not have the underlying capacity to learn language by constructing paradigms. PMID- 1934978 TI - Can valid inferences be suppressed? PMID- 1934979 TI - Children's early understanding of false belief. AB - We investigated 3-year-olds' understanding of the representational capability of the mind by examining whether they would acknowledge that they had entertained a wrong belief. As in previous studies, children very often judged that they had believed a Smarties tube contained pencils when these were revealed as the true content, even though they had stated "Smarties" before the tube had been opened. Under another condition, when the tube was first presented, children mailed a picture into a postbox of what they thought was inside (Smarties). When asked "When you posted your picture, what did you think was in here (the tube)?" the great majority of children answered correctly with "Smarties". Additionally, children nearly always stated that the posted card displayed a picture of Smarties, and that the tube really contained pencils. On the traditional task, children may give the wrong answer because they are biased to make judgments about belief states on the basis of known physical reality. The posting task made it possible for children simultaneously to focus on physical reality and acknowledge false belief. PMID- 1934980 TI - Understanding covert recognition. AB - An implementation of Bruce and Young's (1986) functional model of face recognition is used to examine patterns of covert face recognition previously reported in a prosopagnosic patient, PH. Although PH is unable to recognize overly the faces of people known to him, he shows normal patterns of face processing when tested indirectly. A simple manipulation of one set of connections in the implemented model induces behaviour consistent with patterns of results from PH obtained in semantic priming and interference tasks. We compare this account with previous explanations of covert recognition and demonstrate that the implemented model provides the most natural and parsimonious account available. Two further patients are discussed who show deficits in person perception. The first (MS) is prosopagnosic but shows no covert recognition. The second (ME) is not prosopagnosic, but cannot access semantic information relating to familiar people. The model provides an account of recognition impairments which is sufficiently general also to be useful in describing these patients. PMID- 1934981 TI - Did two farmers leave or three? Comment on Starkey, Spelke, and Gelman: numerical abstraction by human infants. PMID- 1934982 TI - Social roles and utilities in reasoning with deontic conditionals. AB - A set of experiments is reported in which a new formulation of deontic thinking is tested. This is that people represent subjective utilities inherent in conforming to or violating deontic statements, along with the social dynamics of these statements. The experiments used Wason's selection task and tested people's understanding of conditional permission. In the first two experiments, familiar scenarios referring to family interactions were used. In the third, an imaginary business content was used. In both cases it was apparent that people's thinking depended on their representation of the utilities associated with the agent of a permission statement (the party who lays down the rule) and the actor (the party whose behaviour is its target). The results are discussed as favouring an explanation in terms of mental models, rather than the schema theories which have dominated this field hitherto. PMID- 1934984 TI - Epidemiology, diagnosis, and treatment of polymyalgia rheumatica. PMID- 1934983 TI - Aspirin, salicylates, and nonsteroidal anti-inflammatory drugs: new class labeling and medical practice. PMID- 1934985 TI - Risk factors of anti-inflammatory drugs. PMID- 1934986 TI - Modern management of rheumatoid arthritis. PMID- 1934987 TI - Current topics in the diagnosis and treatment of scleroderma. AB - Scleroderma has been viewed as one of the most discouraging diffuse connective tissue diseases to manage. In the last 10 years, we have seen major advances in our understanding of its pathogenesis. New techniques for earlier diagnosis widen the window of opportunity for therapeutic intervention. A multitude of possible disease-modifying therapies are under study. Advances in molecular biology, including increased understanding of the cellular messages controlling the process of fibrosis, provide additional hope for better treatment. Clinical research in this disease is inhibited by limited numbers of patients and the difficulties encountered in evaluating progression and response to treatment. All patients with suspected or newly diagnosed scleroderma should be evaluated at a medical center actively engaged in the research of this disease. Such research is likely to accelerate the gains made during the last decade. PMID- 1934988 TI - Diagnosis, pathogenesis, and management of reflex sympathetic dystrophy syndrome. PMID- 1934989 TI - Methotrexate in the treatment of inflammatory arthritis. PMID- 1934990 TI - Update: slow acting anti-rheumatic drugs in rheumatoid arthritis. PMID- 1934991 TI - Fibromyalgia: an explanation for the aches and pains of the nineties. AB - Fibromyalgia is a common rheumatologic disorder. Societal costs, based on medical expenses, lost wages, lost tax revenue and compensation expenditures, are significant. Diagnosis, dependent primary on subjective patient reports, can be confirmed by mapping alterations in electrical resistance or temperature. The most effective available medication regimens are only moderately effective in the treatment of fibromyalgia and have undesirable side effects. Hypnotic, injection and electroprobe therapy appear reasonable alternatives. PMID- 1934992 TI - A behavior setting assessment for community programs and residences. AB - Using the concept of person-environment fit to determine the effectiveness of residential and program placements for chronic psychiatric clients requires systematic and concrete information about these community environments in addition to information about the clients themselves. The conceptual and empirical development of the Behavior Setting Assessment (BSA), a measure based on Barker's behavior setting theory, is described. Use of the BSA with 28 residences (117 settings) and 11 programs (176 settings) from two community support systems demonstrated that all 293 settings assessed could be described and analyzed in terms of differences in their demands for self-care skills, food preparation and consumption, verbal/cognitive responses, and solitary or group activities. The BSA is an efficient measure for obtaining specific, concrete information about the behavioral demands of important community environments. PMID- 1934993 TI - Improving client outcomes: the Kansas technical assistance consultation project. AB - A central problem in the design and implementation of mental health services is how to transfer relevant information to the active practitioner. Traditional methods of knowledge transfer, such as professional journals and workshops, appear to have uneven results at best. Outreach consultation services, here described as technical assistance, holds promise as an effective and efficient vehicle for transferring relevant knowledge necessary to improve professional practice. This report describes the technical assistance consultation project jointly sponsored by the University of Kansas, School of Social Welfare and the Kansas State Department of Mental Health and Retardation. It is argued that an important function of this project was symbolic as well as substantive. State departments of mental health and major public universities can work in consort to assist professionals and programs perform at a maximum level. Such an effort re casts the manner in which these institutions are traditionally viewed by those engaged in direct practice. A case example is provided. PMID- 1934994 TI - Barriers to individualized community support services: the impact of some current funding and conceptual models. AB - Methods now used to fund and monitor community support services for long term mentally ill persons work at cross purposes to the goals they are to promote. Commonly, community supports are offered through a limited number of programs selected by systems managers. Often these programs have a primary goal of providing treatment or helping consumers achieve some higher purpose with only a secondary focus on the consumer obtaining wanted goods and services needed to develop and sustain an individualized community support network. Consumer directed vouchers offer a preferred alternative to these approaches. PMID- 1934995 TI - Developing and maintaining a coordinated system of community-based services to children. AB - The Child and Adolescent Service Systems Program (CASSP) encourages the development of "systems of care" for disturbed children and their families, based on interagency collaboration and community involvement. The experience of the South Shore mental health catchment area near Boston points to several principles for promoting effective collaboration: 1) mobilization of concerned and influential community members, 2) respect for the autonomy and interdependence of systems, 3) appreciation of divergent perspectives, and 4) commitment to shared goals. The realization of these principles depends on certain supports: staff training, flexible agency structure, sanction from a strong community and state and federal legislative support. PMID- 1934996 TI - Conjugal violence: changing attitudes in two northern native communities. AB - In recent years, North American society has begun to recognize the tragic extent of conjugal violence in our homes. Family violence knows no social boundaries and tragically our native peoples have suffered its full impact on their homes and communities. This article reports the findings of case studies of two Arctic communities and compares their responses to family violence before oil and gas development and after. The communities are situated in the centre of the recent exploration for hydrocarbon resources in the Beaufort Sea and have experienced the direct social impacts of this industrial activity. Thus, they provided an excellent opportunity to analyze the relationship between industrial development and violence within the home. The research applied a model developed by Blishen et al (1979), developed specifically for northern communities. The model analyzed the community's social processes and functioning on a continuum from "communitarianism" (social integration) to "privatization" (social isolation). This research collected data comparing conjugal violence before and after development and explored how individuals would respond to family violence and where they would go for help in addressing this problem. The analysis revealed that the communities held different levels of communitarianism and privatization before hydrocarbon development accelerated. After development, both communities experienced increased responses to family violence which were both communitarian and privatized in nature. Previous to development, the respondents tended to avoid situations of family violence and when confronted with it they often did not know how to respond. The findings indicated that conjugal violence has been present in native communities for a long time and it was incorrect to suggest that it was a new phenomenon blamed on increased development. The data indicated that native communities can and have successfully taken a community-based action on this problem. The data demonstrated that social work intervention focused on the community at large can have a positive impact on changing attitudes and stimulate community-based action. And there exists a danger that the social/human service worker may "professionalize" the problem, thereby removing the sense of responsibility from the community and "privatizing" the solution. The article's contribution lies in its critical assessment of traditional human service intervention with individuals and the structures of northern society. And, the paper challenges the professional helpers to broaden their strategies to include innovative community-based approaches. PMID- 1934997 TI - The pre-intake drop-out at a community mental health center. AB - Characteristics of patients who failed to appear for their intake interviews at a community mental health center were contrasted with those who did follow through with their appointments. Findings suggest that characteristics associated with dropping out are likely to vary with patient groups. Show rates for adults who were seeking help for themselves were significantly related to parental status and the length of time from the day of scheduling an intake interview until that appointment. Patient-therapist gender matches were related to the probability of children showing for intake interviews. PMID- 1934998 TI - The malignant catarrhal fever complex. AB - Malignant catarrhal fever (MCF) is defined as a clinicopathological syndrome caused by related herpesviruses and acquired from persistently infected wildebeest and sheep. There is convincing epidemiologic and virologic evidence that Alcelaphine herpesvirus 1 (AHV1) causes the wildebeest-derived disease (WD MCF). Present knowledge suggests that a herpesvirus related to AHV1 may be associated with some cases of the non-wildebeest-associated disease (NWA-MCF). However, this virus possibly represents a passenger virus not related with the ultimate cause of the disease. Moreover, evidence for the role played by sheep as the reservoir for the agent of NWA-MCF is not convincing and awaits confirmation. PMID- 1935000 TI - Human and animal herpesviruses. PMID- 1934999 TI - Simian agent 8--a herpes simplex-like monkey virus. AB - This review summarizes the most recent information on Simian Agent 8, a herpes simplex-like monkey virus. The agent has a broad host range and--besides the classical morphogenesis (budding at the internal nuclear membrane)--the virus gets enveloped at all cytoplasmic membranes including the plasma membrane; strikingly it carries a rather prominent tegument. Regarding its sequence arrangement SA8 can be grouped to the E-type genomes. It has a G + C-content of 69% and a total DNA-homology with HSV-1 of 31%. The glycoproteins gC and gE are largely type-specific; whereas gB and gD as well as ICP35, ICP8 and the major capsid protein represent well conserved proteins of the simplexviruses. The type common epitopes of gB and gD induce cross-reacting antibodies, which are even involved in cross-neutralization. PMID- 1935001 TI - The diversity and unity of Herpesviridae. AB - The family herpesviridae contains over 100 viruses endogenous to humans and to a wide variety of eukaryotic organisms. Inclusion in the family is based on architecture of the virion. The viruses differ significantly with respect to base composition and sequence arrangements of their DNAs, but share many biologic properties including the ability to remain latent in their hosts. On the basis of their biologic properties the herpesviruses have been classified into three subfamilies, i.e. alphaherpesvirinae, betaherpesvirinae and gammaherpesvirinae. The members of each subfamily share many properties including greater conservation and colinear arrangements of their genes. As a rule, more than one herpesvirus has been isolated from animals of economic importance and both humans have yielded viruses belong to all three subfamilies of the herpesviridae. PMID- 1935002 TI - The Scala naturae revisited: evolutionary scales and anagenesis in comparative psychology. AB - Recent suggestions that evolutionary scales have a place in theorization about the evolution of behavior have been based on the concept of anagenesis, formerly associated with notions of biological progress. An associated concept is that of grades, often used as units of anagenetic advance. Advocates of anagenetic analysis in comparative psychology cite the writings of biologists Bernard Rensch, Julian Huxley, George Gaylord Simpson, and Stephen Jay Gould to support the usefulness of anagenesis but treat the positions of each of these theorists as if they were the same. In fact, they differ considerably in their definition of anagenesis and in its application to specific issues in evolution. The anagenetic approach is criticized as axiological and frequently anthropocentric. Although the formation of grades can be useful, a sequence of grades must not be assumed to represent historical stages in the evolution of specific structures or behaviors. PMID- 1935003 TI - Behavioral thermoregulation and immobilization: conflicting demands for survival. AB - In three studies, core temperatures of immature chicks rose during immobilization induced by simulated predation and fell rapidly when immobilization terminated. Immobilization termination was predicted by proximity of the core temperature to the daily resting core temperature of adult fowl. Although immobilization duration increased with age and was shorter in cold and hot environments, immobilization terminated at the same core temperature at all ages and ambient temperatures. The common termination temperature and pattern of temperature change across all Ss suggests that immobilization is terminated in response to the demand that the rising core temperature be behaviorally maintained within a vital range. The generality of this finding was confirmed in a fourth study with preweanling kittens during exhibition of the transport response--an immobilization reaction with a different evolutionary history. These findings reveal that when immobilization and behavioral thermoregulation present conflicting survival demands for avian and mammalian young, the control of core temperature assumes behavioral priority. PMID- 1935004 TI - An evolutionary analysis of psychological pain following human (Homo sapiens) rape: IV. The effect of the nature of the sexual assault. AB - Mental pain is hypothesized to manifest an adaptation for analyzing and coping with social problems that would have reduced inclusive fitness in human (Homo sapiens) evolutionary history. We examined this hypothesis in the psychological pain of 790 rape victims. Reproductive-aged and postreproductive-aged victims were more likely than prereproductive-aged victims to have experienced vaginal intercourse and to have had sperm present in the reproductive tract. As predicted, vaginal intercourse constituted the most psychologically devastating form of sexual assault for reproductive-aged women. Nonreproductive-aged victims were not more traumatized by vaginal rapes. When rapes included ejaculation in the victim's reproductive tract, reproductive-aged victims may have been more traumatized. These results suggest that the psychology that regulates mental pain processes information about the nature of the sexual act in the event of a woman's rape. PMID- 1935005 TI - Asymmetrical hand use in rhesus monkeys (Macaca mulatta) in tactually and visually regulated tasks. AB - Asymmetrical hand use by rhesus monkeys (Macaca mulatta) was investigated in a series of tactually and visually guided tasks. The 1st experiment recorded manual preferences of 29 monkeys for solving a haptic discrimination task in a hanging posture. There was a left-hand population bias: 21 monkeys had a left-hand bias, 4 a right-hand bias, and 4 no bias. The 2nd experiment, 4 tasks with 23 to 51 monkeys, investigated the critical components of the 1st experiment by varying the posture (hanging, sitting, or tripedal) and the sensory requirements (tactile or visual). Posture influenced hand bias, with a population-level left-hand bias in hanging and sitting postures, but an almost symmetrical distribution in the tripedal posture. A left-hand bias was found for both sensory modalities, but the bias was stronger in the tactual tasks. Results suggest a possible right hemisphere specialization in the rhesus for tactile, visual, or spatial processing. PMID- 1935006 TI - Analyses of feeding lateralization in the small-eared bushbaby (Otolemur garnettii): a comparison with the ring-tailed lemur (Lemur catta). AB - Feeding related lateralization was examined in a population of 23 small-eared bushbabies (Otolemur garnettii). The three measures used to determine lateralization were food reaching, holding, and manipulation. Sex and age differences were found, with adult females showing a strong right bias and adult males a left bias. Juvenile males were weakly lateralized and less consistent across measures than adult animals. The use of standard scores to assess lateralization allowed species comparisons to be made. The results of this study were compared with results from a previous study on lateralization in the ring tailed lemur (Lemur catta). Species comparisons found sex differences to be a stronger factor in lateralization than species differences. PMID- 1935007 TI - Acquisition of a relative class concept by an African gray parrot (Psittacus erithacus): discriminations based on relative size. AB - We report that an African gray parrot (Psittacus erithacus), Alex, responds to stimuli on a relative basis. Previous laboratory studies with artificial stimuli (such as pure tones) suggest that birds make relational responses as a secondary strategy, only after they have acquired information about the absolute values of the stimuli. Alex, however, after learning to respond to a small set of exemplars on the basis of relative size, transferred this behavior to novel situations that did not provide specific information about the absolute values of the stimuli. He responded to vocal questions about which was the larger or smaller exemplar by vocally labeling its color or material, and he responded "none" if the exemplars did not differ in size. His overall accuracy was 78.7%. PMID- 1935008 TI - Anxiety and maternal aggression in house mice (Mus musculus): a look at interindividual variability. AB - The hypotheses were tested that mouse motherhood is accompanied by decreased reactivity to aversive stimuli and that female anxiety is inversely related to the probability of displaying intense forms of postpartum aggression. Outbred Swiss female mice were tested for anxiety in a light/dark choice test when virgin, pregnant, or lactating, and then tested for maternal aggression (5-min exposure to a male intruder) on postpartum Day 7. Anxiety declined in pregnant and lactating females when compared with virgin animals. Furthermore, females who displayed higher scores of postpartum fighting were less anxious in the previous test regardless of reproductive stage. Part of interindividual variability in postpartum aggression might thus be related to differences in the extent to which individuals perceive and react to anxiogenic situations. In addition, the higher emotionality characterizing the C57BL/6 and DBA/2 inbred strains may be responsible for the lack of a clear-cut exhibition of maternal aggression in these two strains. PMID- 1935009 TI - Cluster analysis of clinical data measured in the surgical intensive care unit. AB - A set of 13 extensively used hemodynamic, ventilatory and gas analysis variables are measured (on-line or off-line) on 200 patients in an intensive care unit (ICU) during the 6 h immediately following cardiac surgery. In order to identify both low- and high-risk patterns, a clustering method is applied to these data at three equidistant observation times. Application of the divergence criterion allows a quantitative evaluation of the diversity between the clusters identified, showing that the two patterns are really distinct in the 13-D space. The same criterion is then used to find possible subsets of variables capable of maintaining, in time, an effective separation power. The latter always include the cardiac index (CI), representative of cardiac performance, and two indices related to respiratory efficiency and metabolic rate, i.e., the carbon dioxide production index (VCO2I) and the arterio-venous oxygen difference (avO2D). PMID- 1935010 TI - Utility of combining two diagnostic tests. AB - Methods for evaluating a single diagnostic test with reference to the disease prevalence in a given population include sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. Patient disease status and, ultimately, the treatment course is determined by the outcome of these diagnostics. The advantage of ordering a single diagnostic test, or series of diagnostic tests is a concern of physicians. How much information is gained from using the results of two diagnostic tests, each designed to detect the same disease? Combining tests may be the optimal methodology for determining the disease status of the patient. We propose a systematic strategy for optimizing (minimizing alpha and/or beta errors) the combination of two diagnostic tests. This strategy is then illustrated by the use of data from Doppler ultrasound and ocular pneumoplethysmography in detecting carotid artery disease. PMID- 1935011 TI - GAMEES: a probabilistic environment for expert systems. AB - This paper describes GAMEES (Graphical Modelling Environment for Expert Systems), an interactive graphical environment for building and processing Belief Networks and Influence Diagrams. We review the existing systems designed for analogous purposes, and, after a brief introduction to Belief Networks and Influence Diagrams, we describe the graphical interface, discuss algorithms for probabilistic inference on these networks and illustrate the current implementation of GAMEES. The system has been designed for being integrated within wider expert systems and actually it is part of the Therapy Advisor module within an expert system for the management of anemic patients. PMID- 1935012 TI - CANEST: a microcomputer program for estimating cancer in a cohort. AB - Certain diseases and symptoms carry an overrepresentation of cancer. To be able to measure the strength of such an association it is necessary to be able to predict cancer development in the group being observed. A computer program for computers running under the MS DOS operating system has been developed for this purpose. The program is written in the CLIPPER programming language. The estimates are based on incidence and prevalence data from the Swedish Cancer Registry for the years 1958 to 1986. The program also computes confidence intervals based on the Poisson distribution. The results can be printed out or exported to other programs for further analysis. PMID- 1935013 TI - Simulation program for estimating statistical power of Cox's proportional hazards model assuming no specific distribution for the survival time. AB - Small sample properties of the maximum partial likelihood estimates for Cox's proportional hazards model depend on the sample size, the true values of regression coefficients, covariate structure, censoring pattern and possibly baseline hazard functions. Therefore, it would be difficult to construct a formula or table to calculate the exact power of a statistical test for the treatment effect in any specific clinical trial. The simulation program, written in SAS/IML, described in this paper uses Monte-Carlo methods to provide estimates of the exact power for Cox's proportional hazards model. For illustrative purposes, the program was applied to real data obtained from a clinical trial performed in Japan. Since the program does not assume any specific function for the baseline hazard, it is, in principle, applicable to any censored survival data as long as they follow Cox's proportional hazards model. PMID- 1935014 TI - A computer filing system for drug use in a pregnancy consultation service. AB - A computerized database for documenting drug use in pregnancy was set up on a personal computer. Summaries of the information available from the literature on more than 700 drugs taken during pregnancy have already been entered and are currently in use. This reliable, cheap, handy, and personal system (the first available on the topic) may be a potentially useful instrument not only for drug consultation services, but for individual physicians, too. PMID- 1935015 TI - VTM--an image-processing system for measuring ocular torsion. AB - This paper reports a new, fast, accurate realization of an image-processing method of measuring ocular torsion (rotation of the eyeball around the visual axis) called Video Torsion Measurement (VTM). The method is to cross-correlate the two grey-level distributions of an arc of the iris from two separate images using a fast image processor card interfaced to an IBM-AT compatible computer. The card (Matrox MVP-AT) is supplied with a library of low-level functions for controlling the hardware operations of the board and the VTM system software, which is written in the C programming language, incorporates these low-level functions to interface with the MVP-AT board as well as carrying out the data acquisition and processing algorithms. These programs: acquire an image of an iris illuminated by a single infrared (IR) light source; threshold this image in order to identify the pupil; calculate the pupil area and locate the centre of the pupil using a centre-of-gravity algorithm; record the grey-level distribution along an arc 256 pixels long at a selected radius from the pupil centre; carry out an FFT on this (interpolated) grey level distribution; store the parameters of this reference FFT and cross-correlate the comparable iral grey-level distribution from other test images of the same eye in order to determine the amount of torsional rotation of the test images relative to the reference image. This system is interactive and is designed for operation in a clinical testing situation with a minimum of operator intervention. The VTM system has a resolution of the order of 0.1 deg depending on the arc radius used and it has been validated in two ways: by using it to measure known torsional rotations of an artificial iris-like pattern and also by direct simultaneous comparison of measures on the same human iris images from VTM and those from the standard 35 mm photographic procedure of measuring torsion. PMID- 1935016 TI - Examination of comorbid anxiety in psychiatric inpatients. AB - Seventy-three percent of 90 psychiatric inpatients had a coexisting anxiety disorder. There were few differences between patients with or without coexisting anxiety on more than 100 clinical and demographic variables that were tested. Patients who had an anxiety syndrome before the onset of their major psychiatric disorder also showed few differences when compared with patients whose anxiety started coincident to or after another DSM-III axis I disorder. The concept of primary/secondary anxiety disorder may not be useful when applied to a cross section of psychiatric inpatients. PMID- 1935017 TI - Personality traits associated with panic disorder: change associated with treatment. AB - Eighty-two subjects with panic disorder completed the Personality Diagnostic Questionnaire (PDQ) before treatment and again after a period of relatively stable improvement 3 years later. At baseline, panic subjects scored higher than normal control subjects, who had been matched for age and sex, on avoidant, dependent, histrionic, and paranoid personality subscales. Improvement in panic symptoms after 3 years was associated with reductions in these same subscale scores. Examination of individual items that distinguished panic from normal subjects showed themes of dependency, lack of self-confidence, emotional instability, and sensitivity to criticism that reflected demoralization in the panic disorder subjects. To a large extent, the findings reveal nonspecific, state-dependent effects of panic and agoraphobic symptoms on the personality functioning and morale of patients with panic disorder. PMID- 1935018 TI - Affective disorder: the new imperium. AB - Eugen Bleuler formulated schizophrenia as a disjunctive category based on universal, dimensional phenomena that were regarded as pathognomonic of the disorder. In consequence, schizophrenia came to dominate diagnostic practice in American psychiatry. This report suggests that affective disorder has been formulated in a similar way, and with a similar result. The nature of disjunctive categories is examined and their replacement by conjunctive categories for schizophrenia and affective disorder is anticipated. PMID- 1935020 TI - Anorexia nervosa associated with Klinefelter's syndrome. AB - A second case of anorexia nervosa associated with Klinefelter's syndrome is described. Gender identity problems were thought to have been significant in this adolescent. PMID- 1935019 TI - Alcohol problems in psychiatric patients: 5-year course. AB - Little is known about the occurrence and course of alcohol problems in patients with affective syndromes treated in psychiatric facilities. We have shown previously that a high proportion of such patients abused alcohol. In a 5-year follow-up of patients in the initial study, a large majority had a remission of their alcohol problems lasting at least 6 months, although many of these patients had subsequent relapses. Using survival analyses, we found that alcohol dependence indicators, previous chronicity of alcohol problems, and a diagnosis of schizoaffective disorder predicted poor outcome (specifically, longer time to remission of the alcohol problems). However, these factors were unrelated to receiving alcohol-specific treatment during the 5 years. Severity of social/occupational alcohol problems did not predict poor outcome, but did predict alcohol-specific treatment (detoxification, rehabilitation, Alcoholics Anonymous [AA], or Antabuse). PMID- 1935021 TI - Auditory hallucinations, posttraumatic stress disorder, and ethnicity. AB - The occurrence of intrusive auditory perceptions has rarely been addressed in the study of posttraumatic stress disorder. This study examined the background of 59 individuals with combat-related posttraumatic stress disorder. Subjects with and without auditory hallucinations were compared on demographic military and symptom variables. The occurrence of hallucinations among veterans with posttraumatic stress disorder appears to be more frequent among subjects of Hispanic ethnicity. This may have been related to higher combat exposure or social stresses. The occurrence of hallucinations was unrelated to drug abuse and did not appear to be associated with any particular war. PMID- 1935022 TI - Time experience in melancholia: a comparison between findings based on phenomenology and experimental psychology. AB - The different modes of time experience are based partly on the subjective and partly on the objective concept of time. Consequently, the phenomenon of time is accessible to both phenomenological analysis and experimental psychology. Based on disturbances in time experience in melancholic patients, this report illustrates the type of connection that exists between (qualitative) changes in the phenomenologically deducible "erlebnisimmanente" ego time or "erlebnistranseunte" universal time and (quantitative) experimental time estimation findings. PMID- 1935023 TI - Correlates of hopelessness in psychiatrically hospitalized children. AB - The importance of hopelessness within the study of childhood psychiatric disorders is becoming increasingly apparent. The present study divides a child inpatient sample (age 7 to 12 years) into two groups based on scores from the Kazdin Hopelessness Scale for Children. Comparisons made between the two groups on various measures showed that children with high hopelessness had lower cognitive ability, "difficult child" temperament characteristics, more anxiety, lower self-esteem, and a higher degree of psychopathology than the low hopelessness group. The role of hopelessness in academic success and future psychopathology are discussed. PMID- 1935024 TI - Characterizing organic hallucinosis. AB - A first comprehensive description of the clinical features of patients with the rare diagnosis of organic hallucinosis (OH) is presented, based on information from 11 OH patients among 14,889 patients who presented for evaluation over a 5 year period at our institution. This characterization is of particular current relevance to diagnosticians and clinicians because of the proposed major changes in the diagnostic system for OH in the upcoming DSM-IV and because of the virtual total lack of published information concerning this syndrome. This description includes a listing of the prevalence and mean severity of each symptom. The severity of the symptoms of OH are then compared with those of its crude "functional" equivalent of schizophrenia to determine which symptoms distinguish between these categories. Associated factors are also presented concerning demographics, modes of treatment, level of functioning, and current physical problems associated with OH. PMID- 1935025 TI - Electroconvulsive therapy in the treatment of depression: the impact on length of stay. AB - It has been reported that one advantage to administering electroconvulsive therapy (ECT) for the treatment of depression is that it results in shorter hospitalizations than alternative treatments. The generality of this finding was assessed in the present study, which comprised a retrospective review of 192 admissions for depression. It was found that the prompt initial decision to administer ECT did not reduce the overall length of hospital stays. In fact, patients who were discharged after an initial medication trial actually had shorter admissions than patients treated promptly with ECT. Nevertheless, one subgroup of patients--those who were started on medications, but who were later switched to ECT--had very long admissions. Whether the prompt initiation of ECT will reduce the average length of stay at any individual institution may depend on the numbers of patients who fall into this latter category. This number, in turn, appears to vary widely across institutions. PMID- 1935026 TI - SCID-PANSS: two-tier diagnostic system for psychotic disorders. AB - The SCID-PANSS was developed as a two-tier diagnostic system for psychotic disorders to supplement categorical diagnosis with functional-dimensional assessment. The procedure combines the DSM-III-R Structured Clinical Interview and Rating Criteria (SCID) with those from the Positive and Negative Syndrome Scale (PANSS). The comprehensive 50- to 60-minute interview yields diagnostic classification, plus a profile of 30 symptoms and 10 dimensional scales, including positive and negative syndromes, depression, thought disturbance, and severity of illness. A study of 34 psychotic inpatients assessed by five psychiatrists showed strong interrater correlations (0.85 to 0.97 for summary scales, P less than .0001), supporting the reliability of the SCID-PANSS for clinical and research applications. PMID- 1935027 TI - Further evidence for the significance of a childhood abuse history in psychiatric inpatients. AB - The high prevalence of histories of childhood sexual and physical abuse in inpatient psychiatric populations is documented. In the present study, 38 female inpatients on a psychiatric unit in a teaching hospital were administered an abuse questionnaire and standard measures of psychological distress. Seventy-six percent of the women reported some history of abuse before the age of 16. As predicted, women who reported a childhood history of physical or sexual abuse scored significantly higher on measures of symptomatology and psychopathology as compared with women who did not report an abuse history. Findings confirm the reports of previous researchers, providing further evidence of the generalizability of these observations. PMID- 1935028 TI - Antisocial personality disorder in primary care patients with somatization disorder. AB - Antisocial personality disorder and somatization disorder (SD) have been associated in previous research conducted primarily in patients from the mental health setting. We tested the hypothesis that patients with SD from the primary care setting had less likelihood of having comorbid antisocial personality disorder in a sample of 118 patients with SD. Two methods for diagnosing antisocial personality disorder were used: the Diagnostic Interview Schedule (DIS) and the Structured Clinical Interview for DSM-III-R, axis II (SCID-II). Eight percent of the women and between 18% and 25% (depending on the method used) of the men had antisocial personality, a prevalence rate that clearly exceeds the rate found in the general population. However, in clinical work, only one in 10 women and one in six men with SD will have antisocial personality disorder. These findings are consistent with the shared biological substrate hypothesized for the two disorders. PMID- 1935029 TI - Recommended patch test concentrations for preservatives, biocides and antimicrobials. PMID- 1935030 TI - Cross-reactivity between sensitivity to thimerosal and photosensitivity to piroxicam in guinea pigs. AB - Piroxicam (PXM) is a nonsteroidal anti-inflammatory drug which may induce a photosensitive eruption shortly after administration. We examined whether animals sensitized to thimerosal developed a photosensitivity to PXM. Male Hartley strain guinea pigs were sensitized to thimerosal, thiosalicylate and PXM separately. The open patch test was used to evaluate sensitization to each drug and cross reactions between the drugs. Animals sensitized to thimerosal exhibited positive patch test reactions to thiosalicylate and positive photopatch test reactions to PXM. Both those sensitized to thiosalicylate and to PXM showed positive patch test reactions to PXM. This study demonstrated that thimerosal induces cross sensitivity to PXM in vivo and that the common active component among these compounds may be thiosalicylate. PMID- 1935031 TI - In vivo transcutaneous penetration of nicotinates and sensitive skin. AB - Proclivity to develop irritant reactions and transcutaneous penetration of nicotinates has been investigated in 20 subjects of both sexes, divided into reactors and nonreactors on the basis of the responses to irritant stimuli. 1% sodium lauryl sulphate (patch application for 24 h) and 5% lactic acid in aqueous solutions were used to detect chemical and sensory (subjective) irritation. The vasodilatation induced was measured using a chromameter for 1 h after topical application of the chemical. The area-under-the-curve response and the peak response was used to assess the in vivo penetration of methyl nicotinate (10 mM in aqueous solution). Significant differences were found between reactors and non reactors. Non-reactors showed a significantly decreased area-under-the-curve response and peak response to methyl nicotinate compared to reactors. Nicotinate induced vasodilatation has been used as a model to study transcutaneous penetration of chemicals; the correlation between increased penetration of nicotinates and skin hyperreactivity to irritant substances may suggest an increased transcutaneous penetration of water-soluble chemicals in individuals with sensitive skin. PMID- 1935032 TI - Experimental study of the potential for contact sensitization and cross-reaction of imidazole antifungals. AB - We examined the potential for contact sensitization of miconazole nitrate and croconazole hydrochloride and the cross-reaction between them in guinea pigs by the maximization test of Magnusson and Kligman. Contact sensitivity was induced by croconazole hydrochloride in 5 out of 7 animals which, after being injected with 5% croconazole hydrochloride, underwent a closed patch with 25% croconazole hydrochloride. Contact sensitivity was not induced by miconazole nitrate. The 5 animals sensitized to croconazole hydrochloride were tested with 8 other imidazole antifungals and positive reactions were observed to oxiconazole nitrate in 2 of the 5 animals. This response may be a cross-reaction. PMID- 1935033 TI - Type IV allergy to amide-type local anesthetics. AB - The case of a 45-year-old woman is reported, who developed intense erythema and itching 1 day after subcutaneous (s.c.) injection of a local anesthetic containing mepivacaine and methylparaben. The reaction was attributed to a delayed-type sensitivity to mepivacaine, since mepivacaine gave a positive patch test response and also elicited a delayed sensitivity reaction after s.c. challenges, whereas prick and patch tests with methylparaben, as well as oral challenges, were negative. Interestingly, the patient also showed sensitization to lidocaine, a compound to which she had previously also been exposed. PMID- 1935034 TI - Footwear dermatitis in northern India. PMID- 1935035 TI - Experimental investigation of skin reaction in contact urticaria. PMID- 1935036 TI - Eyelid dermatitis due to cocamidopropyl betaine in an eye make-up remover. PMID- 1935037 TI - Nickel eyelid dermatitis from an eyelash curler. PMID- 1935038 TI - Isothiazolinones (MCI/MI): 200 ppm versus 100 ppm in the standard series. AB - In an attempt to define the optimal test concentration for isothiazolinones, 200 and 100 ppm of 5-chloro-2-methyl-4-isothiazolin-3-one/2-methyl-4- isothiazolin-3 one (MCI/MI) in aq. solution were tested simultaneously in 918 consecutive eczema patients. 3.4% were positive to 200 ppm and 1.7% to 100 ppm, indicating that up to 50% of the cases might have been missed. Among the 33 cases with positive reactions, 21 showed stronger reactions to 200 than to 100 ppm, while 9 had reactions of the same strength. Use tests were carried out in 7 cases, of which 2 were positive. MCI/MI remains a peculiar allergen and some of the problematic factors are: the morphology of the test reactions, the difficulties in tracking down the exposure (past or current relevance), the multisensitivity (MCI/MI plus other allergens), the outcome of the use tests and the optimal test concentration. Our present strategy is to use 200 ppm as an indicator and then to carry out serial dilution and use tests in each "positive" case. PMID- 1935039 TI - Basal transepidermal water loss, skin thickness, skin blood flow and skin colour in relation to sodium-lauryl-sulphate-induced irritation in normal skin. AB - The influence of basal transepidermal water loss (TEWL), skin thickness, blood flow and skin colour on susceptibility to sodium-lauryl-sulphate(SLS)-induced irritant contact dermatitis was studied in 70 healthy volunteers. SLS 0.5% was applied as a patch test. For assessment of basal values and skin response to SLS, bioengineering methods were used: TEWL was measured by an evaporimeter, skin thickness by ultrasound A-scan, blood flow by laser Doppler flowmetry, and skin colour by a colorimeter, using the L*a*b* system of the Commission Internationale de l'Eclairage (CIE). By use of multiple regression analysis, it was demonstrated that basal TEWL was substantially related to skin susceptibility to SLS, high basal TEWL predicting an increased susceptibility to SLS. Also increased light reflection from the skin, indicating a 'fair' skin, was found to be associated with increased susceptibility to SLS. PMID- 1935040 TI - A comparison of expression of surface-bound immunoglobulin E on antigen presenting cells in cutaneous tissue between patients with allergic, irritant and atopic dermatitis. AB - The expression of surface-bound immunoglobulin E by dendritic cells within cutaneous tissue has been compared in atopic and contact dermatitis. 45 patients were recruited into 4 groups using clinical criteria and patch testing to a standard series of allergens: atopic (12 cases), allergic contact dermatitis (14 cases), irritant contact dermatitis (10 cases) and the control group (9 cases); using clinical criteria and patch testing to a standard series of allergens. Skin biopsies from each patient were analysed by the indirect immunofluorescence technique. This differentiated 3 patterns of cutaneous IgE distribution: (i) no detectable cutaneous IgE; (ii) detection of IgE solely within the dermis; (iii) detection of IgE within both epidermis and dermis. Detection of IgE within the epidermis was always associated with the presence of IgE within the dermis. In each case, IgE was surface-bound by dendritic cells. Immunoglobulin E was detected within both epidermis and dermis in skin biopsies from 8 (66.7%) atopic patients and 2 (20%) patients with irritant contact dermatitis. No other cases demonstrated IgE deposition within both the epidermis and dermis. Atopic patients were significantly more likely to have detectable IgE deposition, within both epidermis and dermis, than patients with contact dermatitis (allergic and irritant groups combined, p = 0.0011) or controls (p = 0.0049). This finding suggests that the demonstration of IgE within both epidermis and dermis supports a diagnosis of atopic dermatitis. It would therefore be of value in differentiating between atopic and contact dermatitis, where clinical diagnosis is in doubt. PMID- 1935041 TI - Contact and photocontact allergy to oxybenzone and mexenone. PMID- 1935042 TI - Frequency of contact sensitization to Euxyl K 400. PMID- 1935043 TI - Airborne contact dermatitis from coleus in a housewife. PMID- 1935044 TI - Allergic contact conjunctivitis due to timolol in eyedrops. PMID- 1935045 TI - Allergic contact dermatitis from brilliantine. PMID- 1935046 TI - Hydrocortisone sensitivity: a prospective study of the value of tixocortol pivalate and hydrocortisone acetate as patch test markers. PMID- 1935047 TI - Pilocarpine allergic contact and photocontact dermatitis. PMID- 1935048 TI - A case of contact allergy to Kathon CG in the United States. PMID- 1935049 TI - Ewe milkers and hand eczema. PMID- 1935050 TI - Nickel content of fingernails from hospital cleaners. PMID- 1935052 TI - Contact dermatitis from MC 903, a topical vitamin D3 analogue. PMID- 1935051 TI - Allergic contact dermatitis from Tektamer 38 (dibromocyanobutane). PMID- 1935053 TI - Euxyl K 400: a new sensitizer in cosmetics. AB - Euxyl K 400 is a preservative for cosmetics and toiletries containing 2 active ingredients, 1,2-dibromo-2,4-dicyanobutan and 2-phenoxyethanol. 2057 consecutive patients with contact dermatitis were patch tested with Euxyl K 400 2.5% pet. and ethanol. A positive patch test occurred in 24 patients (1.2%). The source of sensitization was traced in 8 patients to their cosmetics. Both leave-on and rinse-off products were responsible. Further patch tests with Euxyl K 400 0.5% pet. and phenoxyethanol 5% pet. were performed in 11 patients. A positive patch test to phenoxyethanol was detected in 1 of them. Only 3 patients showed a mild reaction to Euxyl K 400 0.5%. A provocative use test with a lotion preserved with Euxyl K 400 0.1% was positive in 5 of these 11 patients. Patients with Euxyl K 400 sensitivity showed a high prevalence of positive patch tests to other common ingredients of cosmetics. Since the use of Euxyl K 400 in cosmetic products is rapidly increasing, it should be included in the patch test series for patients with suspected cosmetic allergy. PMID- 1935054 TI - Ventilatory support alternatives to tracheostomy and intubation: current status of the application of this technology. AB - Intermittent positive pressure ventilation (IPPV) via tracheostomy has been the most common method of providing long-term ventilatory support since the late 1950s. Likewise, intubation for the delivery of IPPV is standard treatment for acute ventilatory failure. Because of poor patient acceptance of elective tracheostomy, numerous reports of complications by these invasive methods, and the recent development of noninvasive ventilatory assistance by intermittent positive airway pressure (NV-PAP), there has been increasing interest in all forms of noninvasive ventilatory support. This report reviews the current application of noninvasive ventilatory support alternatives in both the acute and long-term settings. Assistive technology for the noninvasive evacuation of airway secretions, which facilitates up to 24-hour, long-term noninvasive ventilatory support is also discussed. We conclude that wider familiarity with and application of these techniques are warranted. PMID- 1935055 TI - Clarification of the role of CT scan in the acute evaluation of blunt abdominal trauma. AB - We reviewed 100 patients sustaining blunt trauma whose initial evaluation included an abdominal computed tomographic scan (CT) to assess the role of this modality in managing these patients. Indications for CT scan were suspicion of abdominal injury based on mechanism of injury (46), tenderness (22), falling hematocrit (9), hematuria (5), pain (4), and hyperamylasemia (1). Thirty-four patients had abdominal injury, and four scans identified non-traumatic pathology; 66 patients had no evidence of abdominal injury. There were no additional abdominal injuries detected during the hospitalizations. Mechanism of injury was the only indication for CT scan in 20 patients, none of whom had evidence of abdominal injury. CT scan charges for these 20 patients accounted for 5.5% of the total hospital bill ($204,070). Hospital costs would have been reduced by $11,270 if these patients had been followed clinically. Fifteen patients with soft tissue contusions and normal CT scans were hospitalized less than 72 hours. Room and other hospital charges accounted for 38.5% of the hospital bill; these are costs that would have been saved if these patients had been discharged from the emergency service. Several conclusions can be made from this study. First, abdominal CT scan is a sensitive test for abdominal injury. Secondly, patients without objective signs of abdominal injury whose other injuries warrant admission allowing further observation should be followed clinically and do not need the additional expense of abdominal CT scan. Finally, mechanism of injury alone is not an indication for CT scan. PMID- 1935056 TI - Consensus conference. Diagnosis and management of asymptomatic primary hyperparathyroidism. National Institutes of Health. PMID- 1935057 TI - Post-op. PMID- 1935058 TI - Addictophobia. PMID- 1935060 TI - Interhospital transport audit criteria for helicopter emergency medical services. AB - A quality assurance audit of all interhospital patient transports from 17 June 1985 through 31 December 1989 by Connecticut's critical care helicopter system was performed to determine the number of medically appropriate and justified flights. There were 1,839 transports reviewed using nationally established criteria. Flights not fulfilling any of these criteria (n = 401) were reviewed in detail by a panel consisting of medical and nursing representatives. During this case by case review, additional acceptable criteria for transport were developed. The audit determined that 1,792 (97%) of interhospital transfers were justified for helicopter emergency medical transport. The use of these national criteria along with the proposed additional criteria is recommended to health care personnel in the decision to transport a patient to a tertiary care hospital by air. In addition, these criteria should be prospectively utilized by aeromedical flight programs for quality assurance review of appropriateness of helicopter interhospital requests. PMID- 1935059 TI - The doctor as fiduciary: the Moore case. PMID- 1935061 TI - Diagnostic potential of contrast MRI in lumbar schwannomas. AB - Contrast enhancement in magnetic resonance imaging (MRI) is fast becoming a valuable means of diagnosing spinal pathology. The paramagnetic contrast agent, gadopentetate dimeglumine, used since 1986, delineates extradural, extramedullary intradural, as well as intramedullary lesions without myelography. However a combination of contrast MRI and water-soluble contrast myelography may prove especially useful in diagnosing mobile lesions in the lumbar region, particularly involving the cauda equina. Nerve root attachment (small spherical areas of void signal) and visualization of both the rounded cephalic and caudal ends were two other features delineated well on MRI. We report four cases of lumbar schwannomas where MRI was used alone or in conjunction with water-soluble contrast myelography to make the diagnosis. PMID- 1935062 TI - Fifty years of psychopharmacology. An interview with Benjamin Wiesel, M.D.. Interview by Alex A. Cardoni. PMID- 1935063 TI - Luck and the president's health. PMID- 1935064 TI - Tobacco smoke and risks for non-smokers. PMID- 1935065 TI - Practices around periodic cancer screening by physicians in primary care specialties. AB - Questionnaires and information packets were distributed to 121 physicians in primary care specialties in central Connecticut to ascertain how periodic cancer screening is performed and monitored. Results of a baseline survey of 52 respondents (51% of active practitioners) are presented here. Only one quarter of respondents noted some formal mechanism in place within their practice to encourage periodic screening of patients. We estimate that only 20-30% of physicians complete cancer screening activities during routine office visits, although respondents noted this to be the most common type of patient encounter. Relatively few physicians reported reliance on either memory aids (17%) or office staff (20%) to prompt screening recommendations. Three of four respondents noted that the sole mechanism they utilize to initiate cancer screening is physician chart review. Likewise, follow-up of scheduled screening activities relies predominantly on chart review or patient review at the time of a subsequent office visit. Use of "tickler files" or scanning of computerized records are considerably less common practices. These data suggest that physicians in primary care practices often function without specific mechanisms to facilitate performance and improve follow-up of health promoting activities. PMID- 1935066 TI - Pathologic stage I and II Hodgkin's disease. Long-term results at three Connecticut hospitals. AB - Three radiation therapy departments in Connecticut (Uncas on Thames Hospital, Norwich; Yale-New Haven Hospital, New Haven; and the Hospital of Saint Raphael, New Haven) have consistently used the strategy of staging laparotomy with splenectomy for clinical stage I and II Hodgkin's disease patients with primary radiation therapy as initial therapy for most pathologic stage (PS) I and II patients. From 1971 through 1986, 239 PS I and II patients were treated at these three institutions and 94% received radiation therapy alone as initial treatment. With a minimum follow-up time of one year and a maximum follow-up time of 18 years (mean: 7.3 years), only 19 (8%) of the 239 patients have ultimately died of Hodgkin's disease. Two factors were responsible for the low death rate due to Hodgkin's disease: 1) 176 patients (74%) went into complete remission following initial therapy and did not experience a relapse; and 2) 63 patients relapsed following initial therapy; however, subsequent salvage therapy was successful in 44 (70%) of these 63 patients. The overall 10-year and 18-year survival rates were 81% and 78%, respectively. Staging laparotomy with initial radiation therapy for most PS I and II patients remains an important and highly successful strategy for Hodgkin's disease. PMID- 1935068 TI - Quality assurance--how did we come to this? PMID- 1935067 TI - Obstructing cancers of the right and left colon: critical analysis of perioperative risk factors, morbidity, and mortality. AB - Significant hospital mortality has been observed in right-sided obstructing colonic cancer patients but remains unexplained. The medical records of 52 patients with obstructing colonic cancer seen between 1980-88 were reviewed to identify prognostic factors influencing mortality when carcinoma involved either the right or the left segments of the colon. The mean age, sex, incidence, and distribution of perioperative risk factors and rate of postoperative complications were comparable between the two groups. Right colonic cancer patients had a higher incidence of advanced disease (16 of 19 had Dukes C and D tumors). Their mortality was higher than that of their counterparts (21% vs 9%), correlating primarily with advanced cancer stage rather than with preoperative risk factors or technical (operative) complications. Though the difference in mortality rates is not statistically significant, patients with obstructing cancers of the right colon, compared to their left counterparts, are hospitalized in more advanced stages of disease and have a worse prognosis. PMID- 1935070 TI - Overturn the gag rule. PMID- 1935069 TI - Consensus conference. Clinical use of botulinum toxin. National Institutes of Health. PMID- 1935071 TI - An unrestrained spending spree. PMID- 1935072 TI - The Moore case and the doctor patient relationship. PMID- 1935073 TI - Wild animals as the source of infection with Yersinia pseudotuberculosis in Shimane Prefecture, Japan. PMID- 1935074 TI - Evaluation of methods for examination of antibody response after infection with Yersinia enterocolitica O:3. PMID- 1935075 TI - Yersinia enterocolitica surveillance in Belgium (1979-1989). PMID- 1935076 TI - Immune response to flagellar antigens in human infections with Yersinia enterocolitica. PMID- 1935077 TI - Immunoglobulin isotypes produced by mice experimentally infected with Yersinia sp. PMID- 1935078 TI - Yersinia enterocolitica: antigenic components with diagnostic potential. PMID- 1935079 TI - The V antigen of yersiniae: an overview. PMID- 1935080 TI - Renal insufficiency in mice experimentally infected with Yersinia pseudotuberculosis. PMID- 1935081 TI - Colonization of Yersinia enterocolitica serovar O3 in the intestines of mice. PMID- 1935082 TI - Experimental infection of mice with Yersinia strains bearing or not bearing the virulence-associated plasmid. PMID- 1935083 TI - Uptake of killed Yersinia enterocolitica cells by epithelial cells in the Peyer's patches of mice. PMID- 1935084 TI - Comparative evaluation of various media for the detection of pathogenic Yersinia enterocolitica. PMID- 1935085 TI - Development of antisera to detect virulent Yersinia enterocolitica, Shigella and Escherichia coli enteroinvasive. PMID- 1935086 TI - The epidemiology of Yersinia enterocolitica infection in the British Isles 1983 1988. PMID- 1935087 TI - Adhesion of yersiniae to rabbit intestinal constituents: role of outer membrane protein YadA and modulation by intestinal mucus. PMID- 1935088 TI - Expression of the virulence plasmid-determined protein YOP1 and HeLa cell invasiveness of Yersinia enterocolitica O:3. PMID- 1935089 TI - Phenotypic characterization and virulence of O8 Yersinia strains isolated in Europe. PMID- 1935091 TI - Molecular cloning of Yersinia enterocolitica O:3 rfb region: evidence that temperature regulates the rfb region at the transcriptional level. PMID- 1935090 TI - Chromosomal marker for the 'high pathogenicity' phenotype in Yersinia. PMID- 1935092 TI - Molecular biology of Yersinia pseudotuberculosis large plasmid pVM82. PMID- 1935093 TI - Plasmid-mediated characteristics of Yersinia pseudotuberculosis strains isolated in Italy from humans, cattle and swine. PMID- 1935094 TI - Preparation of monoclonal antibody to V antigen from Yersinia pestis. PMID- 1935095 TI - Persistent survival of attenuated Yersinia pestis organisms with coexistence of chondroitin sulfate colloidal iron within guinea pig macrophages as an initial step of the induction of potent antiplague immunogenesis. PMID- 1935096 TI - Beta-lactamases of strains of Yersinia enterocolitica biovar 6 isolated from foods. PMID- 1935097 TI - Antimicrobial susceptibility of pathogenic Yersinia enterocolitica strains in the British Isles. PMID- 1935098 TI - Isolation of Yersinia from the resected appendix. PMID- 1935099 TI - Comparative isolation of Yersinia spp. from avian wildlife by different methods. PMID- 1935100 TI - Yersinia enterocolitica bacteremia: an analysis of thirty-six patients in Denmark and a review of the literature. PMID- 1935101 TI - Yersinia enterocolitica and other enteric pathogens in patients with suspected appendicitis. PMID- 1935103 TI - Yersiniosis in children: diagnostics and clinical manifestations. PMID- 1935102 TI - New observations on acute and chronic disease associated with Yersinia enterocolitica infection. A 10-year follow-up study on 458 hospitalized patients. PMID- 1935104 TI - Isolation of Yersinia from appendices of patients with acute appendicitis. PMID- 1935106 TI - Cases of Yersinia pseudotuberculosis infection having diagnostic criteria of Kawasaki disease. PMID- 1935105 TI - Invasive disease due to Yersinia enterocolitica in children with beta-thalassemia major. PMID- 1935107 TI - Several aspects of Yersinia pseudotuberculosis infection in children. PMID- 1935108 TI - Renal complications of Yersinia pseudotuberculosis infection in children. PMID- 1935109 TI - Yersinia pseudotuberculosis infection in the mountain area. PMID- 1935111 TI - Isolation of yersiniae from sewage. PMID- 1935110 TI - Yersinia enterocolitica O:3 antibodies in slaughterhouse employees, veterinarians, and military recruits. Occupational exposure to pigs as a risk factor for yersiniosis. PMID- 1935112 TI - Urease-negative strains of Yersinia enterocolitica and related species isolated from human and nonhuman sources. PMID- 1935113 TI - Yersinia pseudotuberculosis infection in children due to untreated drinking water. PMID- 1935114 TI - Direct isolation of Yersinia enterocolitica from stool specimens of patients with intestinal disorders. PMID- 1935115 TI - Occurrence of Yersinia enterocolitica in pork products from northern Taiwan. PMID- 1935116 TI - Colonization in the tonsils of swine by Yersinia enterocolitica. PMID- 1935117 TI - Comparison of plasmid DNA among different serogroups of Yersinia pseudotuberculosis. PMID- 1935118 TI - Enteropathogenic Yersinia enterocolitica and organ-specific autoimmune diseases in man. PMID- 1935119 TI - A molecular basis for antigen homologies of thyroid epithelial cells and plasmid encoded proteins of enteropathogenic Yersinia enterocolitica. PMID- 1935120 TI - Immunoblot analysis of antibody response to Yersinia enterocolitica in patients with reactive arthritis and enterocolitis. PMID- 1935122 TI - The third age, the Third World and the 21st century. PMID- 1935121 TI - Cross-reacting protein antigen of Yersinia enterocolitica is a heat shock protein. PMID- 1935123 TI - Achievements in gynecology 1989-90. PMID- 1935124 TI - The physiology of human relaxin. PMID- 1935125 TI - Biochemical characteristics of human endometrial cells. PMID- 1935126 TI - Functional and structural recovery of the brain in in utero treated hydrocephalic monkeys: follow-up of neurobehavioral development. PMID- 1935127 TI - The apparent paradox of sexual differentiation of the brain. PMID- 1935128 TI - Induction of ovulation with gonadotropins in patients with polycystic ovarian syndrome. PMID- 1935129 TI - Carcinogenic consequences of DNA alkylation. PMID- 1935130 TI - Improvement of cytodiagnosis of ovarian tumors employing monoclonal antibodies. PMID- 1935131 TI - Computerized method for rotational autokeratoplasty. AB - The aim of our study was to formulate the procedure of rotational autokeratoplasty; that is, design the computer system and software necessary to automatically define the parameters of the problem. To achieve this, we used a CCD camera (Nikon) and a microcomputer with an integrated IMAGENIA (Biocom) interface software card (512 x 512 pixels and 100 gray levels), which permitted acquisition and digitalization of photographs of the lesioned cornea. Digitization of the image allowed us to determine the coordinates (x,y) of the points that lay on the lesion periphery as well as the coordinates of the corneal center; i.e., the geometric center of the cornea. The center of trephination and the optimal diameter of trephination can then be calculated as a function of a point situated on the lesion edge. PMID- 1935132 TI - Atropine in keratoplasty for keratoconus. AB - A prospective study of 83 eyes in 76 consecutive patients undergoing keratoplasty for keratoconus is presented in which 1% atropine was routinely given at the end of surgery. No case of permanent mydriasis was seen. The syndrome described in the literature of fixed, dilated pupil after the use of atropine in keratoplasty no longer seems to exist and the warning against strong mydriatics appears unwarranted. PMID- 1935133 TI - Clinical and immunohistologic studies of corneal rejection in the rat penetrating keratoplasty model. AB - We used immunohistologic techniques with a penetrating keratoplasty model in the rat to study the mechanisms of corneal transplant rejection. Thirteen of 14 syngeneic grafts remained clear in contrast to 24 of 26 allogeneic grafts, which had a rejection reaction. Immunohistochemical studies of syngeneic grafts showed only rare inflammatory cells in the central grafts; however, a focal inflammatory reaction made up of macrophages and T-helper/inducer lymphocytes was seen surrounding the sutures and in the wound. In contrast, immunohistochemical studies of allogeneic grafts showed diffuse inflammation throughout the donor and recipient corneas with T-suppressor/cytotoxic cells, T-helper/inducer cells, and macrophages, resulting in destruction of the donor endothelium, neovascularization, and graft failure. Class II antigen expression was seen extensively on Langerhans cells, donor keratocytes, and both the donor and recipient endothelial cells. These findings emphasize the role of early nonspecific inflammation in the wound and around the sutures, and delineate the cellular immune response and class II antigen expression in corneal allograft rejection. PMID- 1935134 TI - Donor cornea bacterial contamination. AB - The incidence of culture-positive cornea rims from 446 consecutive donor corneas cultured at the Doheny Eye Institute between 1986 and 1988 was determined. Both the identity and antibiotic sensitivities of the contaminating organisms were reviewed. Sixty-three (14.1%) of 446 cornea rims were culture-positive, but none of the 63 patients who received these contaminated donor corneas developed endophthalmitis. Streptococcus (26 of 63), Propionibacterium (15 of 63), Stphylococcus (14 of 63) species and diptheroids (8 of 63) were the most common cornea rim contaminants, and in most cases were resistant to gentamicin (i.e., 21 of 26 or 81%, 9 of 15 or 60%, 10 of 14 or 71%, 4 of 8 or 50%, respectively). Virtually all of the gentamicin-resistant bacteria isolated from cornea rims were found to be sensitive to vancomycin. Eye banks should consider the addition of other antibiotics to storage media to reduce donor cornea contamination. Surgeons performing corneal transplantation should also consider these results when selecting antibiotics for use at the time of surgery and in the postoperative period. PMID- 1935135 TI - The effects of fibronectin on the adherence of bacteria to corneal epithelium. AB - The aim of our experiments was to determine whether treatment with topical fibronectin led to increased adherence of Staphylococcus aureus or Pseudomonas aeruginosa to rabbit corneas with epithelial defects. No significant effect of fibronectin was demonstrated. For all strains of S. aureus tested, the number of recoverable organisms was decreased at 24 h compared to 1 h. None of the rabbits developed infectious keratitis. PMID- 1935136 TI - Electron microscopic findings in corneal epithelial basement membrane degeneration. AB - In an attempt to correlate basement membrane changes with clinical symptoms we examined 29 specimens from 28 patients who had undergone corneal epithelial basement membranectomy for corneal epithelial basement membrane degeneration (CEBMD). Twenty-two of the 28 patients were women. Recurrent erosion was the most frequent symptom and occurred in 24 of the 29 eyes. The most common electron microscopic finding was reduplication of the basement membrane with loculated connective tissue. The electron microscopic finding that predicted clinical symptoms was absence of the basement membrane and hemidesmosomes, which occurred in 4 eyes with severe recurrent erosion. PMID- 1935137 TI - Specular microscopy studies on the corneal endothelium after cessation of contact lens wear. AB - We performed specular microscopy on the corneal endothelium of 22 long-term hard contact lens wearers (15-32 years duration) and 22 age- and sex-matched controls. We found polymegethism in users as shown by a significant difference in the coefficient of variation in cell area (p less than 0.01) and pleomorphism as shown by a significant decrease in the percent of 6-sided cells (hexagonality, p less than 0.01). There was no significant difference in cell density and mean cell area between the 2 groups. Contact lens wear was discontinued in five eyes of three patients after they were entered into the study and switched to eye glasses. Specular micrographs were taken up to 60 months after discontinuation of use of the lenses. Comparison of the above parameters before and after discontinuation of the lenses did not show a significant change. However, there was a trend toward improvement in the coefficient of variation in the eyes that were followed the longest. This finding suggests that the morphological changes induced by long-term use of contact lenses may be slowly reversible after prolonged discontinuation of contact lens wear. PMID- 1935138 TI - Effects of intraocular irrigants on the preserved human corneal endothelium. AB - Either a simple balanced salt solution (BSS) or a bicarbonate-buffered, glutathione-containing commercial irrigant (BSS Plus, Alcon Laboratories, Fort Worth, Texas, U.S.A.) may be used during the vitrectomy portion of a corneal transplant procedure. To simulate the conditions present in the anterior chamber during the first few hours after vitrectomy and grafting, we performed in vitro perfusions of stored human corneas using each irrigant and measured corneal thickness over a 3-hour period. Irrespective of the preservation medium used (McCarey Kaufman, Chondroin Sulfate or Dexsol, all from Chiron Ophthalmics, Irvine, California) or duration of storage (2 or 4 days), corneas irrigated with BSS Plus exhibited significantly (p less than .05) decreased thickness compared with their paired mates irrigated with BSS. In ultrastructural studies performed on postperfusion corneas, there was a tendency toward improved surface morphology in the in vitro BSS Plus-perfused tissue. This study shows that in vitro corneal thickness after preservation is significantly irrigant dependent, with BSS Plus providing the essential ingredients to promote the corneal endothelial pump function. PMID- 1935139 TI - Gentamicin resistance in staphylococcal corneal ulcers. AB - Gentamicin sulfate is frequently included in the initial treatment of suspected bacterial keratitis. We present the gentamicin susceptibility test results for coagulase-negative staphylococci and Staphylococcus aureus isolated from corneal ulcers in nine patients. All were resistant to gentamicin by standard disk diffusion techniques. The minimum inhibitory concentrations were very high, some exceeding the concentration normally achieved by frequent topical application of antibiotics. Clinicians should be aware that strains of staphylococci extremely resistant to gentamicin may cause keratitis. An antibiotic with broad activity against Gram-positive organisms, such as a cephalosporin or vancomycin, should be included as part of the initial therapy for corneal ulcers that might be caused by staphylococci. PMID- 1935140 TI - Toxicity and pharmacokinetics of subconjunctival amphotericin B. An experimental study. AB - The pharmacokinetics and toxicity of subconjunctival (S/C) amphotericin B (AmB) were evaluated in Dutch-belted rabbits. Following the S/C injection of 1,500 micrograms of AmB, corneal and aqueous levels were determined by bioassay. The highest levels were present in the periphery of debrided corneas at 1 h (90.12 +/ 2.4 micrograms/g). The debrided central cornea contained 30.84 micrograms/g, almost double the amount present in the intact central cornea. These levels were transient; in the central intact cornea only 2.08 micrograms/g could be detected at 2 h. Peak aqueous levels were low (0.95 +/- .24 micrograms/mL in debrided corneas at 1 h). The S/C injection of 1,500 micrograms of AmB in sodium deoxycholate produced a severe inflammatory response in the conjunctiva, episclera, iris, anterior chamber, and superior rectus muscle that persisted 10 days. Injection of sodium deoxycholate alone produced a similar but less severe response. PMID- 1935141 TI - Recurrent corneal erosion: pathology of corneal puncture. AB - Recurrent corneal erosion is a difficult disorder to treat. Despite conventional therapy, some patients continue to have episodes of erosion. Recent literature suggests the efficacy of corneal puncture, which is thought to induce adherence of the epithelium and basement membrane to the anterior stroma. We performed multiple corneal punctures with 23-, 25-, 27-, and 30-gauge needles on one patient who underwent penetrating keratoplasty 7 weeks later. We found that an insertion depth of 0.1 mm was sufficient to cause the production of new basement membrane and fibrocytic reaction in the anterior stroma. Analysis of the pathologic specimen supports the use of the larger 23- and 25-gauge needles, and cautions against the use of small gauge needles, especially 30-gauge, for this procedure. PMID- 1935142 TI - Factors responsible for tear ferning. AB - The biochemical agents involved in fern formation on drying tears were investigated by studying the different patterns of ferning of tears from normal and pathological eyes, mucus glycoprotein, saliva, serum, and various salt solutions. We conclude that the ferning phenomenon observed when a drop of tears is allowed to dry at room temperature on a clean microscope slide is to a large extent determined by the electrolyte concentration, especially the ratio of monovalent sodium and potassium ions to divalent calcium and magnesium ions. The presence of a biopolymer is essential, but this need not specifically be mucus as previously thought. The test may therefore be useful clinically in indicating the need for further tear analysis. PMID- 1935143 TI - Fluorescence of blood-stained cornea. AB - Corneal blood staining represents deposition of hemoglobin and its breakdown products within the cornea. Pathologic examination of these corneas typically reveals degenerating endothelial cells and keratocytes. These degenerative changes have typically been attributed to the blunt trauma itself or to toxicity of the erythrocytic debris (a "localized hemosiderosis"). Another possible mechanism for this injury, however, is porphyrin-induced photosensitivity. Examination of frozen sections of an acutely blood-stained human cornea demonstrated fluorescence within all layers of the cornea, similar to that seen with hematoporphyrin derivative. The production of cytotoxic oxygen species within the blood-stained cornea exposed to light may contribute to endothelial and keratocyte degeneration. Limiting light exposure of blood-stained corneas or eyes with hyphemas might theoretically reduce light-induced and porphyrin mediated toxicity. PMID- 1935144 TI - Epikeratoplasty for pellucid marginal corneal degeneration. AB - Two patients with advanced pellucid marginal corneal degeneration (PMCD) received bilateral epikeratoplasty grafts ranging in diameter from 9 to 12 mm. Corneal astigmatism was greatly reduced in every case and the possibility of resuming contact lenses for daily wear, obtained after surgery, provided patients with a satisfactory best corrected visual acuity. Peculiarities of surgical procedure and clinical experience are reported. PMID- 1935145 TI - Collagen shields and perforated corneal ulcers. PMID- 1935146 TI - Ibuprofen in patients with severe sepsis. PMID- 1935147 TI - Lethal catatonia and the neuroleptic malignant syndrome. PMID- 1935148 TI - Derived pulmonary capillary hydrostatic pressure: time for clinical application? PMID- 1935149 TI - Evoked potentials: a decade later. PMID- 1935150 TI - Effect of ibuprofen in patients with severe sepsis: a randomized, double-blind, multicenter study. The Ibuprofen Study Group. AB - OBJECTIVE: To evaluate the safety and physiologic actions of ibuprofen in patients with severe sepsis. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Three university hospital medical ICUs. PATIENTS: Twenty-nine patients with clinical evidence of sepsis and the need for hemodynamic monitoring with a pulmonary artery flotation catheter. INTERVENTIONS: Thirteen patients received placebo and 16 received ibuprofen that consisted of 600 mg (n = 11) or 800 mg (n = 5) iv over 20 mins, followed by three 800-mg doses administered as a rectal solution every 6 hrs. The initial iv dose was given within 4 hrs of the presumptive diagnosis of sepsis. MEASUREMENTS AND MAIN RESULTS: The peak circulating total ibuprofen concentration after the iv dose (49.4 +/- 4.5 micrograms/mL, mean +/- SEM) was higher than peak concentrations after the three rectal doses (17.0 +/- 2.7, 16.4 +/- 3.0, 16.0 +/- 3.1 micrograms/mL). Both routes of ibuprofen administration were well tolerated. Frequent monitoring for gastrointestinal bleeding and assessment of renal and hepatic function failed to demonstrate significant differences between ibuprofen and placebo. Because a trend for reduced creatinine clearance was observed at 8 hrs in the ibuprofen group, nephrotoxicity of this drug in sepsis cannot be excluded. Temperature decreased significantly within 4 hrs of the initial dose of investigational therapy in patients who received ibuprofen (38.5 +/- 0.3 degrees to 37.0 +/- 0.2 degrees C, p less than .001). However, despite this significant change in temperature, we were unable to detect significant differences in hemodynamic and respiratory values or survival when ibuprofen-treated patients were compared with controls. CONCLUSIONS: Ibuprofen was well tolerated when administered iv and rectally to patients with severe sepsis, although drug absorption was poor with the rectal route. Significant antipyretic effects of ibuprofen were demonstrated. Although an excellent safety profile characterized ibuprofen in this study, the absence of ibuprofen-associated toxicity may have been secondary to poor rectal absorption of the drug. Our results support the continued clinical investigation of ibuprofen in sepsis, using an all-intravenous route of administration. PMID- 1935151 TI - Double lumen umbilical venous catheters in critically ill neonates: a randomized prospective study. AB - OBJECTIVES: To compare relative efficacies and complications associated with the use of double lumen vs. single lumen umbilical venous catheters in critically ill neonates. DESIGN: Prospective randomized control trial. SETTING: Neonatal ICU. PATIENTS: Forty-three critically ill neonates. INTERVENTIONS: Group 1 patients (n = 20) received single lumen umbilical venous catheters and group 2 patients (n = 23) received double lumen catheters. A record of the following information was kept: demographic data including diagnosis and indication for umbilical venous catheter insertion, catheter tip location, length of catheterization (days), number of additional iv catheters and complications (sepsis, hepatic necrosis, thrombosis, or mechanical complications). MEASUREMENTS AND MAIN RESULTS: Double lumen umbilical venous catheters were well tolerated and were associated with no significant increased risk of mechanical complications when compared with single lumen umbilical venous catheters. The number of additional iv catheters required (0.8 +/- 0.1 [SD]) was significantly (p less than .05) less in the double lumen umbilical venous catheter group as compared with additional iv catheters required (2.3 +/- 0.8) in the single lumen umbilical venous catheter group. CONCLUSION: Double lumen umbilical venous catheters are well tolerated for short-term use, decrease the need for additional venous catheters in critically ill neonates, and may not significantly increase the risk of mechanical complications when compared with single lumen umbilical venous catheters. PMID- 1935152 TI - Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study. AB - OBJECTIVE: To determine whether correction of acidemia using bicarbonate improves hemodynamic variables and tissue oxygenation in patients with lactic acidosis. DESIGN: Prospective, randomized, blinded, cross over study. Each patient sequentially received sodium bicarbonate and sodium chloride. The order of the infusions was randomized. PATIENTS: Ten patients with metabolic acidosis, increased arterial plasma lactate concentrations (greater than 2.45 mmol/L), and no severe renal failure (creatinine less than 250 mumol/L [less than 2.3 mg/dL]). METHOD: Sodium bicarbonate (1 mmol/kg body weight) or equal volume of sodium chloride was injected iv at the beginning of two successive 1-hr study periods. Period order was randomized. Arterial and venous blood gas measurements, plasma electrolytes (sodium, potassium, chloride), osmolality and lactate, 2,3 diphosphoglycerate (DPG), and oxygen hemoglobin affinity, hemodynamic variables, oxygen delivery, and oxygen consumption measurements were obtained before and repeatedly during the 1-hr period after the injection of bicarbonate or sodium chloride. MEASUREMENTS AND MAIN RESULTS: Sodium bicarbonate administration increased arterial and venous pH, serum bicarbonate, and the partial pressure of CO2 in arterial and venous blood. Hemodynamic responses to sodium bicarbonate and sodium chloride were similar. Tissue oxygenation (as estimated by oxygen delivery, oxygen consumption, oxygen extraction ratio, and transcutaneous oxygen pressure) was not modified. No changes in serum sodium concentration, osmolality, arterial and venous lactate, red cell 2,3-DPG levels, or hemoglobin affinity for oxygen were observed. CONCLUSION: Administration of sodium bicarbonate did not improve hemodynamic variables in patients with lactic acidosis, but did not worsen tissue oxygenation. PMID- 1935153 TI - Effect of short-term muscle relaxation on neonatal plasma volume. AB - OBJECTIVES: To study the effect of pancuronium-induced muscle relaxation on circulating plasma volume. DESIGN: A prospective, controlled study. Consecutive infants who were paralyzed with pancuronium and a comparative group who were not paralyzed during mechanical ventilation were studied. SETTING: Neonatal ICU of a regional referral university-affiliated hospital. PATIENTS: Newborn infants weighing greater than 1700 g who required respiratory assistance within 24 hrs of birth and who were free of congenital heart disease, sepsis, or blood loss were eligible for entry into the study. Infants who received colloid infusions during the study period were excluded. A total of 17 consecutive infants (nine paralyzed and eight nonparalyzed control infants) were studied. Four paralyzed infants and one nonparalyzed infant received colloid infusions before the completion of the study and were excluded from the final analysis. MEASUREMENTS: Plasma volume was measured three times in the paralyzed infants: a) immediately before the first dose of pancuronium, b) after 12 to 24 hrs, and c) greater than or equal to 12 hrs after the return of muscle activity, but before extubation. Plasma volume in the nonparalyzed, control infants was measured at the time of intubation, 12 to 24 hrs after commencing mechanical ventilation, and 12 hrs after extubation. Plasma volume was measured using the Evans blue dye dilution technique. RESULTS: There were no changes in the plasma volume or blood volume in the three measurements among both the paralyzed and nonparalyzed infants. CONCLUSION: Pancuronium-induced muscle relaxation in mechanically ventilated newborn infants weighing greater than 1700 g did not alter circulating plasma volume in 24 hrs. PMID- 1935154 TI - Arterial-venous pH differences and tissue hypoxia in patients with fulminant hepatic failure. AB - OBJECTIVE: A recent report suggested that, for hypotensive patients, tissue acidemia is best monitored by simultaneous estimates of arterial pH, mixed venous pH, and bicarbonate. This method of detecting tissue acidemia may therefore apply to fulminant hepatic failure patients, who are known to have a high frequency of covert tissue hypoxia. In the present study, both arterial pH and mixed venous pH and bicarbonate were compared in 22 patients with fulminant hepatic failure. Blood samples were drawn from the pulmonary artery and radial artery and this blood was analyzed to determine oxygen delivery and consumption. The arterial pH, mixed venous pH, and bicarbonate were compared using an oxygen flux test to determine the optimal method of demonstrating tissue hypoxia in this group of patients. DESIGN: A prospective study. SETTING: The Liver Unit of our institution. PATIENTS: Patients (n = 22) with fulminant hepatic failure admitted between January 1989 and January 1990. INTERVENTIONS: Patients were studied before and after an infusion of prostacyclin. MEASUREMENTS AND RESULTS: The findings of this study suggest that pH and bicarbonate differences in arterial and mixed venous blood samples were not indicative of tissue hypoxia in patients with fulminant hepatic failure. By contrast, measurement of oxygen consumption after the infusion of prostacyclin, with the demonstrated increase in oxygen uptake, provided a more accurate indication of covert tissue hypoxia. CONCLUSIONS: In critically ill patients with a hyperdynamic circulation, such as those patients with fulminant hepatic failure, an oxygen flux test remains the best method of determining the presence of covert tissue hypoxia. PMID- 1935156 TI - Is neonatal inspired gas humidity accurately controlled by humidifier temperature? AB - OBJECTIVE: To investigate: a) the relationship between humidifier temperature and inspired gas humidity and b) the effect of insulating the inspiratory tube on "rainout" (condensate). DESIGN: Observational study. SETTING: Regional neonatal unit in a university hospital. PATIENTS: Forty-eight infants receiving assisted ventilation, of whom 31 infants were nursed in incubators and 17 under radiant heaters. MEASUREMENTS AND MAIN RESULTS: Despite always maintaining humidifier temperature greater than 34.7 degrees C, inspired gas humidity decreased below the American National Standards Institution minimum of 30 mg H2O/L on 35 of 479 occasions. At a humidifier temperature of 36 degrees C, inspired gas humidity varied between 17 and 43 mg H2O/L. In incubators set at a temperature of 34.1 +/- 1.3 (SD) degrees C, inspired gas humidity was linearly related to humidifier temperature, but with wide scatter (p less than .001, r2 = .28). In cooler incubators set at 32.9 +/- 1.8 degrees C, inspired gas humidity varied inversely with humidifier temperature. This variation was attributed to condensate due to inspired gas cooling within the incubator. Insulation of the inspiratory tubing reduced condensate by only 15%. CONCLUSIONS: Inspired gas humidity cannot be predicted reliably from humidifier temperature. Accurate control will require a new generation of humidifiers that measure inspired gas humidity. PMID- 1935155 TI - Effect of vasoactive treatment on the relationship between mixed venous and regional oxygen saturation. AB - OBJECTIVE: To evaluate the relationship between the mixed venous (SvO2), hepatic, and femoral venous oxygen saturations before and during sympathomimetic drug infusions. DESIGN: Case series. SETTING: Tertiary care center. PATIENTS: Twenty four ICU patients: postoperative open-heart surgery patients (n = 12), patients with septic shock (n = 8), and patients with acute respiratory failure (n = 4). INTERVENTIONS: In postoperative open-heart surgery patients and patients with respiratory failure, cardiac output was increased by at least 25% following therapy with either dobutamine or dopamine. Patients with septic shock were treated with either dopamine or norepinephrine to correct hypotension. MEASUREMENTS AND MAIN RESULTS: Vasoactive drug infusions increased cardiac index and oxygen delivery by 34% and oxygen consumption by 8%. SvO2 increased (62.6 +/- 6.7% vs. 69.5 +/- 6.0%, p less than .001). Although cardiac index was the most important determinant of SvO2, the correlation between cardiac index and SvO2 was weak (r2 = .32). The hepatic and femoral venous saturations also increased (49.0 +/- 12.1% vs. 59.4 +/- 9.8%, p less than .01, and 51.9 +/- 16.6% vs. 63.4 +/- 9.8%, p less than .001, respectively) in response to vasoactive treatment. The mean gradient between SvO2 and hepatic venous saturation was 11.9 +/- 8.7% and was independent of the clinical condition and baseline SvO2. The hepatic venous oxygen saturation increased in parallel with SvO2 regardless of the initial SvO2 value. CONCLUSIONS: The individual values of SvO2 have no predictive value concerning regional oxygen transport. The parallel increase in SvO2 and hepatic venous oxygen saturation suggests that the vasoactive treatment did not compromise splanchnic oxygenation. PMID- 1935157 TI - Serial multimodality-evoked potentials in severely head-injured patients: diagnostic and prognostic implications. AB - OBJECTIVES: To assess the prognostic reliability of multimodality-evoked potentials and to evaluate the diagnostic implications and define the limits of these evoked potentials. SETTING: An ICU in a university hospital. DESIGN: Prospective clinical study. PATIENTS: Seventy-three severely head-injured patients aged 10 to 75 yrs. METHODS: Serial recording of brainstem auditory evoked potentials and somatosensory-evoked potentials between days 1 and 21 after trauma. Comparison between evoked potential findings and prognosis, along with clinical data. RESULTS: Considering the single recordings of both brainstem auditory-evoked potentials and somatosensory-evoked potentials, the accuracy of prognostication in predicting a bad outcome was good only for severely abnormal brainstem auditory-evoked potentials. Serial brainstem auditory-evoked potential recordings and simultaneous recordings of brainstem auditory-evoked potentials and somatosensory-evoked potentials proved to be good prognostic indices in predicting a favorable outcome. Brainstem auditory-evoked potentials correlated well with brainstem reflexes and with pupil asymmetries but did not correlate with Glasgow Coma Scale scores. CONCLUSIONS: Serial recording and the use of a multimodality approach provided the best prognostic capabilities. The main diagnostic implications were: a) the possibility of detecting brainstem compression by means of brainstem auditory-evoked potentials before the appearance of pupil abnormalities; b) the usefulness of brainstem auditory-evoked potentials in monitoring brainstem function in patients undergoing high-dose barbiturate therapy. The main limitations of evoked potentials were the occurrence of peripheral acoustic damage, the electromagnetic sources of artifacts in the ICU, and the administration of ototoxic drugs. PMID- 1935158 TI - Systolic and diastolic time intervals in the critically ill patient. AB - OBJECTIVE: The waveform of the first derivative of thoracic electrical bioimpedance was used to calculate systolic time intervals of the cardiac cycle, preejection period/left ventricular ejection time ratio, and diastolic time intervals, isovolumic relaxation period/filling time ratio. DESIGN: Prospective clinical study. Waveforms were examined from 913 normal and abnormal tracings from a thoracic electrical bioimpedance monitor. This monitor was coupled to a two-channel strip-chart recorder that identified preejection period/LV ejection time and isovolumic relaxation period/filling time in 86% of the tracings. SETTING: Two university-affiliated hospitals and one community hospital. PATIENTS: We assessed 100 subjects (ranging in age from 17 to 93 yrs) under various conditions. MEASUREMENTS AND MAIN RESULTS: Data from 15 normal subjects were used as a reference series to define normative values. Preejection period/left ventricular ejection time ratio was 0.35 +/- 0.1 (SD) and was consistent with data from systolic time intervals derived from simultaneous study of the ECG recording, carotid artery tracing, and phonocardiography. The diastolic time ratio (isovolumic relaxation period/filling time) was 0.4 +/- 0.2, in agreement with normal values derived by echocardiography and angiography. In a subgroup of 17 critically ill patients, a correlative study of simultaneously measured thoracic electrical bioimpedance, nuclear stethoscope, and radionuclide ventriculography was conducted. Systolic functions were compared by the ejection fraction derived by preejection period/left ventricular ejection time ratio displayed on the thoracic electrical bioimpedance monitor and by the radionuclide technique, and were found to be 57 +/- 13.8% and 58 +/- 8.6%, respectively (r2 = .49; y = 4.06x + 0.94; p less than .02; n = 17). Increased diastolic time ratios with normal or near-normal systolic time intervals were documented in nine (53%) of 17 critically ill patients with low systolic index. CONCLUSION: Both systolic and diastolic time intervals can be investigated noninvasively at the bedside by the thoracic electrical bioimpedance technique to provide a better understanding of left heart function. PMID- 1935159 TI - Efficacy of continuous arteriovenous hemofiltration with dialysis in patients with renal failure. AB - OBJECTIVE: To document the efficacy of continuous arteriovenous hemofiltration with dialysis following renal failure, without protein restriction, and to explore the magnitude and clinical applications of total daily urea clearance. DESIGN: A noncomparative, descriptive account of a case series. Data were collected prospectively and analyzed retrospectively. SETTING: A tertiary care facility in a statewide emergency medical services system. PATIENTS: Twenty-eight patients with renal failure were supported by continuous arteriovenous hemofiltration with dialysis in a critical care unit during a 14-month period (21 patients with multitrauma; three patients with soft tissue infections; and four patients with multisystem organ failure who had been transferred from other hospitals). Renal failure was most commonly due to multisystem organ failure or associated with adult respiratory distress syndrome. RESULTS: Continuous arteriovenous hemofiltration with dialysis days totaled 308 (mean 10.9). All patients received full protein alimentation (mean protein load 131 g/day). The blood urea nitrogen concentration was controlled, generally to 40 to 75 mg/dL (14.3 to 26.7 mmol/L) within 3 to 5 days. Total daily urea clearance ranged from 15 to 21 g/day. Five (18%) of the 28 patients survived. CONCLUSION: Continuous arteriovenous hemofiltration with dialysis appears to be effective for the control of blood urea nitrogen and clearance of urea. This modality also permits full protein alimentation. Total daily urea clearance can be calculated easily and may have important clinical uses and implications. PMID- 1935160 TI - Experience with phenylephrine as a component of the pharmacologic support of septic shock. AB - OBJECTIVE: To evaluate the use of the selective alpha 1-adrenergic receptor agonist phenylephrine in the hemodynamic support of patients with septic shock. DESIGN: Retrospective analysis of clinical use of phenylephrine. SETTING: Surgical ICU in a university hospital. PATIENTS: Thirteen patients with septic shock (diagnosed by defined criteria) requiring pharmacologic support for the treatment of hypotension. INTERVENTIONS AND MAIN RESULTS: All patients underwent invasive hemodynamic monitoring followed by volume resuscitation and inotropic support to reverse flow-dependent oxygen consumption and lactic acidosis. Patients with persistent hypotension (mean arterial pressure [MAP] less than 65 mm Hg) and vasodilation (systemic vascular resistance index [SVRI] less than 1500 dyne.sec/cm5.m2 received phenylephrine at iv infusion rates of 0.5 to 9 micrograms/kg.min to maintain MAP greater than 70 mm Hg. MAP, SVRI, left ventricular stroke work index, and stroke volume index were significantly (p less than .05) increased after phenylephrine administration and at the time of highest oxygen consumption (VO2). Cardiac index was unchanged initially but increased at the time of highest VO2 (p less than .05). Pulmonary artery occlusion pressure and heart rate were unchanged. Average baseline VO2 increased from 145 to 200 mL/min.m2 and oxygen delivery (DO2) increased from 447 to 597 mL/min.m2 during phenylephrine treatment (p less than .05). Blood lactate concentrations decreased and urine output increased significantly (p less than .05), while serum creatinine concentrations remained unchanged during phenylephrine therapy. CONCLUSIONS: Treatment with phenylephrine was associated with beneficial hemodynamic effects when used to maintain perfusion, while increasing DO2 and VO2 in patients with septic shock. PMID- 1935162 TI - Derived pulmonary capillary pressure changes after smoke inhalation in sheep. AB - BACKGROUND AND METHODS: We determined derived pulmonary capillary pressure and the longitudinal distribution of pulmonary vascular resistance in chronically instrumented sheep with inhalation injury by using analysis of pressure decay curves after pulmonary artery occlusion. RESULTS: There was an increase in derived pulmonary capillary pressure and an increase in the lung lymph flow after smoke inhalation. The pulmonary vascular, arterial, and venous resistances increased significantly in the inhalation group. Pulmonary venous resistance increased proportionately more than pulmonary arterial resistance in the inhalation group. The plasma osmotic pressure-derived pulmonary capillary pressure gradient decreased to a greater extent in the inhalation group than in the control group. CONCLUSIONS: The present experiments suggest that the estimates of derived pulmonary capillary pressure can predict filtration pressure better than pulmonary artery occlusion pressure. The derived pulmonary capillary pressure can be measured easily in man with a pulmonary arterial catheter. PMID- 1935161 TI - Comparison of oxygen consumption measurements: indirect calorimetry versus the reversed Fick method. AB - OBJECTIVE: To compare measurement of oxygen consumption (VO2) by spirometry and the reversed Fick method. DESIGN: Within-patient comparison using simultaneous measurements by the two methods, one previously calibrated on a metabolic simulator. PATIENTS: Twenty sets of observations on eight patients (57 to 83 yrs) requiring mechanical ventilation in a critical care unit. INTERVENTIONS: None during or immediately before the measurements. MEASUREMENTS AND MAIN RESULTS: Duplicate pairs of measurements of VO2 were made with a previously validated spirometric technique and the reversed Fick method (Qt[CaO2 - CVO2]), where Qt is cardiac output, CaO2 is arterial oxygen content, and CVO2 is mixed venous oxygen content. The coefficient of variation of the difference between duplicate measurements by the former technique was only 2.53% compared with 10.4% for the latter. The mean VO2 measurement by the spirometric method was 285.7 +/- 40.7 (SD) mL/min standard temperature and pressure, dry (STPD) and for the reversed Fick method, the mean VO2 measurement was 249.3 +/- 38.5 mL/min STPD. The mean difference was 36.4 +/- 28.5 mL/min STPD (p less than .001). CONCLUSIONS: The repeatability of the spirometric method was four times better than the reversed Fick method. The latter gave a significantly lower value that probably, in part, reflects the VO2 of the lung, which is included in the spirometric method but not in the reversed Fick measurement. PMID- 1935163 TI - Perfusion of the interventricular septum during ventilation with positive end expiratory pressure. AB - OBJECTIVE: To determine whether regional hypoperfusion of the interventricular septum occurs during ventilation with positive end-expiratory pressure. DESIGN: Animal study. ANIMALS: Anesthetized, closed chest dogs (n = 8). INTERVENTIONS: Induction of experimental adult respiratory distress syndrome (ARDS) and then ventilation with 10, 15, and 20 cm H2O of positive end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: Cardiac output and regional interventricular septum blood flow were assessed at control, at induction of experimental ARDS, and at each level of positive end-expiratory pressure. Ventilation with 20 cm H2O of positive end-expiratory pressure decreased cardiac output (-32% vs. control, p less than .05), and did not change absolute, but increased relative (to cardiac output) interventricular septum blood flow. During experimental ARDS and ventilation at 20 cm H2O end-expiratory pressure, there was a redistribution of flow toward the right ventricular free wall (+93%, p less than .001) and the right ventricular part of the interventricular septum (+68%, p less than .01), while flow to the left ventricular interventricular septum and to the left ventricular free wall remained unchanged. Locally hypoperfused interventricular septum areas or findings indicative of interventricular septum ischemia were not observed during positive end-expiratory pressure. CONCLUSIONS: The decrease in cardiac output during positive end-expiratory pressure is not caused by impaired interventricular septum blood supply. The preferential perfusion of the right ventricular interventricular septum indicates increased local right ventricular interventricular septum oxygen-demand and suggests that during positive end expiratory pressure, this part of the interventricular septum functionally dissociates from the left ventricular interventricular septum and the left ventricular free wall to support the stressed right ventricle. PMID- 1935164 TI - Manual resuscitators and spontaneous ventilation--an evaluation. AB - BACKGROUND AND METHODS: Although it is useful in certain clinical situations for manual resuscitator units to be used with spontaneously ventilating patients, there are few data regarding their performance in these settings. We measured the percent-delivered oxygen from 13 adult manual resuscitator units during simulated spontaneous ventilation in the range of respiratory frequency, tidal volume, and oxygen supply in which manual resuscitator units might be used with patients. We also measured the resistive pressure developed during simulated ventilation and at constant inspiratory flow of 50 L/min. RESULTS: Oxygen supply, tidal volume, minute ventilation, and reservoir volume all influenced percent-delivered oxygen, but the most important determinant of percent-delivered oxygen was valve design. Valves incorporating a "disc" element to prevent air entrainment from the expiratory port gave the most efficient oxygen delivery, while "duck-bill" valves did not reliably prevent air entrainment. Only two of the manual resuscitator units tested developed high resistive pressure. CONCLUSION: Reliable administration of high percent-delivered oxygen to spontaneously ventilating patients, while retaining the capability to manually ventilate them, is best achieved by a manual resuscitator unit with a valve of low resistance, incorporating a disc to prevent air entrainment. We recommend that manufacturers indicate on the product information sheet the degree (and confidence limits) to which their manual resuscitator unit presents resistance and delivers oxygen to a spontaneously ventilating subject. PMID- 1935165 TI - Redefining ischemia due to circulatory failure as dual defects of oxygen deficits and of carbon dioxide excesses. PMID- 1935166 TI - Reconsiderations of the routine and preferential use of lidocaine in the emergent treatment of ventricular arrhythmias. AB - OBJECTIVE: Despite a history of widespread use, the utility of lidocaine as an antiarrhythmic and antifibrillatory agent is questionable. The objective of this article is to examine the theoretical basis for the use of lidocaine in light of recent experimental and clinical data. This article reviews the effects of lidocaine on: a) ventricular arrhythmias under ischemic and nonischemic conditions; b) the energy and current requirements for defibrillation; and c) the propensity for asystole during cardiac arrest. DESIGN: A contemporary review of the literature. FINDINGS: There appears to be a theoretical basis for the use of lidocaine in treating ventricular arrhythmias secondary to acute ischemia largely based on voltage- and pH-dependent binding and inactivation of sodium channels by lidocaine under ischemic conditions. However, clinical and experimental data failed to establish enhanced survival following prophylactic treatment for acute ischemic events or when treatment is administered during cardiac arrest. Moreover, there are no data supporting the use of lidocaine in treating sustained and life-threatening ventricular arrhythmias in the absence of acute ischemia. Experimental data demonstrate that lidocaine can reduce countershock efficacy, i.e., increase the current and energy requirements for defibrillation. Experimental and clinical data suggest that the administration of lidocaine increases the propensity for asystole during cardiac arrest. CONCLUSIONS: While lidocaine may possess an antifibrillatory effect under experimental conditions, the clinical relevance of such an effect is questionable. If cardiac arrest occurs, lidocaine has limited utility and may be deleterious secondary to diminished countershock efficacy or lidocaine-induced asystole. Reconsideration of the use of lidocaine should be included in future guidelines for management of cardiac arrest. PMID- 1935167 TI - Lethal catatonia complicated by the development of neuroleptic malignant syndrome in a middle-aged female. PMID- 1935168 TI - Management of lethal catatonia with dantrolene sodium. PMID- 1935169 TI - Improved outcomes from tertiary center pediatric intensive care: a statewide comparison of tertiary and nontertiary care facilities. PMID- 1935170 TI - Enzymology of the acetyl-CoA pathway of CO2 fixation. AB - We know of three routes that organisms have evolved to synthesize complex organic molecules from CO2: the Calvin cycle, the reverse tricarboxylic acid cycle, and the reductive acetyl-CoA pathway. This review describes the enzymatic steps involved in the acetyl-CoA pathway, also called the Wood pathway, which is the major mechanism of CO2 fixation under anaerobic conditions. The acetyl-CoA pathway is also able to form acetyl-CoA from carbon monoxide. There are two parts to the acetyl-CoA pathway: (1) reduction of CO2 to methyltetrahydrofolate (methyl H4folate) and (2) synthesis of acetyl-CoA from methyl-H4folate, a carboxyl donor such as CO or CO2, and CoA. This pathway is unique in that the major intermediates are enzyme-bound and are often organometallic complexes. Our current understanding of the pathway is based on radioactive and stable isotope tracer studies, purification of the component enzymes (some extremely oxygen sensitive), and identification of the enzyme-bound intermediates by chromatographic, spectroscopic, and electrochemical techniques. This review describes the remarkable series of enzymatic steps involved in acetyl-CoA formation by this pathway that is a key component of the global carbon cycle. PMID- 1935171 TI - Parathyroid hormone-related protein: biochemistry and molecular biology. AB - This article critically reviews the current state of knowledge regarding the recently identified and cloned novel hormone parathyroid hormone-related protein (PTHrP). PTHrP is produced by tumors associated with the syndrome of humoral hypercalcemia of malignancy giving rise to the parathyroid hormone (PTH)-like symptoms characteristic of the syndrome. Areas that will be reviewed include identification, purification and cloning, localization, actions, and significance of PTHrP in cancers and normal physiology. The structure and regulation of the PTHrP gene that may be ancestrally related to the PTH gene will also be discussed. Studies in vivo and in vitro with synthetic and recombinant PTHrP sequences and antibodies developed against them have established that the PTH like actions of PTHrP are mediated via the N-terminal sequences, which show some limited sequence homology with PTH. Evidence for PTH and non-PTH-like actions of PTHrP in normal physiology, which implicate a role for PTHrP in fetal and neonatal development, is also presented. PMID- 1935172 TI - In memoriam. Ronald I. N. Greaves (1908-1990). PMID- 1935173 TI - The potential of an equimolar combination of propane-1,2-diol and glycerol as a vitrification solution for corneas. AB - Corneas must first be equilibrated with multimolar concentrations of cryoprotectants if the formation of ice during cryopreservation is to be avoided by vitrification at practicable cooling rates. Rabbit corneas were exposed to equimolar mixtures of the cryoprotectants propane-1,2-diol and glycerol in a Hepes-buffered Ringer's solution containing glutathione, adenosine, 5 mmol/liter sodium bicarbonate, and 6% w/v bovine serum albumin. Endothelial function was assessed by monitoring its ability to control stromal hydration during perfusion of the endothelial surface at 34 degrees C for 6 h. Endothelial morphology was observed by specular microscopy during perfusion and by scanning electron microscopy after perfusion. Endothelial pump activity and structural integrity of the endothelial layer were demonstrated after 20 min exposure at 4 degrees C to a total concentration of 1.4 mol/liter cryoprotectant (i.e., 0.7 mol/liter propane 1,2-diol + 0.7 mol/liter glycerol). Exposure to 2.0 and 3.4 mol/liter cryoprotectant for 20 min at 4 degrees and -5 degrees C, respectively, resulted in initial endothelial damage; but this repaired and a functioning endothelial pump was subsequently demonstrated. Although exposure to 4.1 mol/liter cryoprotectant for 10 min at -10 degrees C caused irreparable damage to 2/4 corneas, reduced dilution temperatures together with increased dilution time allowed exposure to 4.8 and 5.5 mol/liter cryoprotectant with retention of endothelial pump activity. Exposure to 6.1 mol/liter cryoprotectant for 10 min at -15 degrees C caused endothelial damage which was not mitigated by the presence of 2.5% w/v chondroitin sulfate. Endothelial function may be improved by further modification of addition and dilution protocols or by exposure to the cryoprotectants at lower temperatures. PMID- 1935174 TI - The cryoprotective action of synthetic glycolipids. AB - Egg PC vesicles frozen and thawed in the presence of carbohydrate derivatives do not incur damage normally associated with freeze thawing. Treated vesicles maintain membrane integrity as evidenced by the lack of lipid intermixing and maintenance of vesicle size following freezing and thawing. This protection is conferred at a derivative:lipid ratio of 0.4 mol/mol, significantly lower than the amount of carbohydrate required when not attached directly to the vesicle. This result indicates that only the carbohydrate at the vesicle surface is responsible for imparting stability to the membrane. This effect can be modulated by variations in the nature of the surrounding medium or alterations in the structure of the carbohydrate, suggesting that direct interactions between the carbohydrate and membrane occur at the membrane interface which are sensitive to bulk phase properties. PMID- 1935176 TI - Effect of Ca2+ on the cryoprotective action of trehalose. AB - The competitive effect of Ca2+ on the cryoprotective action of carbohydrates has been investigated during freeze-thaw processes of unilamellar egg phosphatidylcholine vesicles. Ca2+ inhibits the cryoprotection achieved by trehalose to a greater extent than other sugars such as galactose, sucrose, and fructose. The cryoprotection by trehalose is also dependent on the Ca2+ concentration in the inside solution of the vesicle, even in the absence of external Ca2+. The competitive effect of Ca2+/trehalose is interpreted as a consequence of the different amount of interfacial water displaced by each compound in their adsorption on the water/lipid interface. PMID- 1935175 TI - Cryosolvents effects on low temperature gel structure of denatured collagen. AB - Water flux and crystallization are major problems for cryopreservation. The gel approach relies on the concept that a biological gel network might sufficiently entrap fluid within its pores, so as to maintain its osmotically inactive under the stresses usually encountered in the course of cryopreservation and limit the extent of crystallization. It could even induce vitrification. The effects of some cryosolvents on the structure of denatured collagen gels were studied as a function of temperature by hydraulic conductivity measurements and electron microscopy observations, so as to explore the porosity and fluid behavior of the gels. Gels formed in the presence of methanol exhibit a large increase in pore size as gelation temperature drops, whereas almost no variation is detected with ethylene glycol, where the porosity is finer. Gels in the presence of ethylene glycol display a larger fluid content, smaller flow rates, and better pressure resistance than those in the presence of methanol. Electron micrographs confirm the variations in gel structures depending on the cryosolvent and the temperature. Rheological measurements also support these observations. Upon rapid cooling, vitrification occurs only in gels with ethylene glycol. Ethylene glycol seems to have a specific interaction with denatured collagen gels which induces a finer network better adapted for trapping fluid osmotically inactive in the course of cryopreservation. PMID- 1935177 TI - Cryomicroscopic determination of the membrane osmotic properties of human monocytes at subfreezing temperatures. AB - Monocytes were isolated from fresh whole human blood and resuspended in Hanks balanced salt solution; a portion of the cells was mixed with an equal volume of 2M dimethyl sulfoxide (DMSO) to form a 1 M solution. Microliter volumes of cell suspension were placed directly onto a computer-controlled cryostage and cooled to a predetermined subzero temperature. Ice was nucleated in the extracellular medium and a continuous video record was made of the subsequent osmotically induced volume changes of individual cells owing to exposure to the concentrated extracellular solutes. Selected micrographs emphasizing the initial transient data were digitized for computer analysis with an interactive boundary tracing algorithm to determine metric parameters of specific cells, and apparent volume changes were measured as a function of elapsed time after nucleation. The Kedem Katchalsky-coupled transport equations were fit to the data using a network thermodynamic model implemented on a microcomputer to determine values for the permeability properties Lp, omega, and sigma. Experiments were performed over the temperature range from -7 degrees to -10 degrees C. Cells pre-equilibrated with DMSO had a lower Lp and a higher activation energy, delta E, than without additive, although the statistical significance of the difference could not be substantiated. It was found that the movement of DMSO across the plasma membrane in response to extracellular freezing was apparently so much smaller than the water flux that values for omega and sigma could not be determined from the data base. PMID- 1935178 TI - Effect of the exposure to chronic-intermittent cold on the thyrotropin and thyroid hormones in the rat. AB - Rats exposed to acute cold (4 degrees C for 2 h), chronic cold (4 degrees C), and chronic-intermittent cold (4 degrees C for 2 h daily) were killed after 1, 2, 3, 4, and 10 days of cold exposure. The control group was maintained at 25 degrees C. In each animal, the plasma concentration of thyrotropine (THS), triiodothyronine (T3), and thyroxine (T4) was determined by radioimmunoassay. At the initial time of exposure, elevations in TSH, T3, and T4 were observed in the rats in each experimental group. However, on the 10th day, in rats exposed to chronic-intermittent cold, TSH, T3, and T4 decreased to values lower than the control values. In animals exposed to acute cold as well as to chronic cold no differences were found, with respect to the controls, in TSH and T4. In rats exposed to acute cold for 10 days, the T3 value was lower than the control value; however, in animals exposed to chronic cold, T3 was same as that in the controls. The results indicate that, in the rat, exposure to chronic-intermittent cold produces an inhibition in the secretion of TSH and thyroid hormones. PMID- 1935179 TI - Abstracts of papers presented at the twenty-eight annual meeting of the Society for Cryobiology, July 7-12, 1991, Leuven, Belgium. PMID- 1935180 TI - Suffering and its professional transformation: toward an ethnography of interpersonal experience. AB - The authors define experience as an intersubjective medium of microcultural and infrapolitical processes in which something is at stake for participants in local worlds. Experience so defined mediates (and transforms) the relationship between context and person, meaning and psychobiology in health and illness and in healing. Building on this theoretical background, an approach to ethnography is illustrated through an analysis of suffering in Chinese society. The embodied memory of a survivor of serious trauma during the Cultural Revolution provides an example. From there, the authors go on to describe a framework of indigenous Chinese categories for the analysis of experience--mianzi (face), quanxi (connections), renqing (situated emotion), bao (reciprocity). The paper concludes with a discussion of the existential limits of this and other anthropological approaches to the study of experience as moral process. PMID- 1935181 TI - Consumption by semen loss in India and elsewhere. AB - Using ethnographical data from a rural site of Oriya culture, the purpose of this article is to show that the Indian obsession regarding the harmful consequences of semen loss does not constitute a specific Indian culture-bound preoccupation, but represents a survival example of a much widespread system of beliefs that can be traced for instance in Western culture to the Hippocratic notion of "back consumption" and the classical concept of gonorrhoea. At the core of this system of beliefs are found ancient conceptions of the nature and functions of semen in human life. These conceptions and their cultural influences incidentally inform us about one of the origins of the reprobation of onanism, as well as one possible way, among many others, for traditional thinking to explain the clinical enigma of depressive syndrome. PMID- 1935182 TI - Women and affliction in Maharashtra: a hydraulic model of health and illness. AB - The anthropological literature on spirit possession cults offers a distinction between voluntary possession or mediumship and involuntary possession or illness. Fieldwork was carried out in a Mahanubhav healing temple. Contradictory interpretations of trance and affliction were found to be held by the different temple inhabitants. Beliefs about the nature of spiritual affliction, its epidemiology and aetiology vary according to gender, family structure and position within the family. One manifestation of affliction is thought to be madness. However, the experience of mental affliction is very varied, for example, the number of family members accompanying an afflicted person, the amount of money made available for treatment, the length of treatment, as well as the less tangible but equally important aspects of treatment such as the degree of empathy and concern felt, all vary according to the afflicted person's gender and status within the family. The inferiority of women's position in society and their precarious belonging in their husband's family comes to the fore in cases of mental illness. The greater shame attaching to women's mental illness means that more women seek temple treatment alone and that the level of family support and involvement is less for women. Recently married women and older childless women fare particularly badly in the division of concern and responsibility for the afflicted. In Maharashtra the recognition and experience of mental affliction varies according to the stage of family development and, most importantly, according to the gender of the patient. PMID- 1935183 TI - Hidden dimensions of power and resistance in the translation process: a south African study. AB - This article examines the social relationships involved in the production of a Xhosa version of the Beck Depression Inventory (BDI). The South African sociopolitical context and the imperatives of the biomedical context are discussed. These play an important role in how the problem of semantic equivalence between translations, and the issue of the imposition of a colonialist, Western psychiatric framework are addressed. After a brief but critical outline of recommended translation techniques, the particular combination of back-translation and committee method employed in this study is presented. An analysis of the social relationships revealed a complex set of interrelated factors affecting the process. The power differential between researcher and back-translators, compounded by their different perceptions of the task, impeded discussion about the instrument. Translators had ostensibly markedly opposed claims to competence to speak for the "true Xhosa language". At a deeper level however, these claims, and indeed the entire translation enterprise, could be seen to be reproducing apartheid structures, regardless of the intention of the participants. The dynamics we describe are particularly salient in the South African context but may also be operative in other contexts. PMID- 1935184 TI - A student nurse's experience in an ICU. PMID- 1935185 TI - Oxygen transport in the blood. AB - Knowledge of how oxygen is dissolved in the blood, transmitted through the bloodstream, and factors that affect oxygen delivery to body cells, is essential to the nursing management of the critically ill patient whose inherent physiologic mechanisms have been compromised by life-threatening illness. This article begins with a simplified review of respiration, progresses through a discussion of oxygen tension in the blood and hemoglobin transport of oxygen, and ends with a discussion of factors that affect the oxyhemoglobin dissociation curve. PMID- 1935186 TI - Quality assurance and the critical care nurse. AB - Care of the critically ill has become increasingly challenging due to demands from external sources to measure the quality and appropriateness of care provided. Quality assurance is the responsibility of every critical care nurse and requires vigilance as well as a knowledge of the principles of standards, monitoring and evaluation. Through quality assurance activities, the contribution of critical care nurses in the achievement of patient outcomes can be measured. Quality assurance challenges us to evaluate the way we practice, and assists us to continuously improve the way we provide care to critically ill patients. PMID- 1935187 TI - Advances in patient care management: the NRCU. AB - The noninvasive respiratory care unit has become an important advance in patient management. The NRCU allows for better use of special-care beds and represents a more cost-effective approach to the care of a number of ventilator-dependent patients or other respiratory patients. This article describes the NRCU, discusses clinical experiences and focuses on practical issues related to patient management in the NRCU. PMID- 1935188 TI - Prolactinoma: a review and case study. AB - Prolactinomas are often characterized by a slow, insidious onset of symptoms. This case study highlights the need for a thorough understanding of the endocrine system and reinforces the importance of history taking and detailed nursing assessment. PMID- 1935190 TI - Heart block post MI. PMID- 1935189 TI - Critical care competency-based orientation. Part 2. PMID- 1935191 TI - The recruitment and retention of critical care nurses: a reader survey. PMID- 1935192 TI - Psychological factors in late-life suicide. AB - A number of psychological factors influence late life suicide, including dysfunctional family and family history of suicide; relational problems throughout life; history of drinking; numerous losses in middle and late life such as the loss of power and control, loss of spouse, and loss of work role; and increasing mental health problems in late life. Depression, the most common mental disorder in later life, is a major precipitating factor in suicide. Alcoholism is another major precipitating factor in late-life suicide. Approximately one-third of all suicides are alcoholics. Many of the same factors which contribute to depression also increase the risk of alcoholism and/or suicide. Loss, stress, loneliness, low self-esteem, and feelings of anxiety, rejection, helplessness, and hopelessness characterize late life alcoholism and depression. Alcoholism, depression, and suicide form a deadly triangle. Family, caregivers, and practitioners need to be aware of the deadly relationship between alcoholism, depression, and suicide in older adults. PMID- 1935193 TI - Suicide in old age: psychotherapeutic intervention. AB - Psychotherapy with suicidal patients can best be planned and conducted after the specific narcissistic incapacities of the patient have been identified through an examination of the clinical history. To which of the suicide-inviting affects (worthlessness, aloneness, murderous rage) is the patient vulnerable? On what exterior sustaining supports has the patient relied in the past to ward them off? What exterior sustaining supports have been lost, and which remain available in the present? What maneuvers must the psychotherapist undertake in order to offset the narcissistic deficiencies of the patient? These questions are addressed as they bear on psychotherapeutic interventions with older patients, and specific problems of countertransference are reviewed. PMID- 1935194 TI - Suicide in the elderly: general characteristics. AB - In this article, general characteristics of suicide in the elderly are discussed. They have the highest suicide rate of any age group, are more determined to die, use "harder" methods, and seem less prone to communicate their suicidal intentions. Furthermore, it seems from recent research that the attitude toward suicide becomes more negative (i.e. no probability of suicide committed by oneself) with increasing age, but at the age of 55 men's attitudes remain negative whereas women's become positive. Approximately at the age of 65 we can see the reverse. The particular factors affecting suicide in old age, such as retirement, relocation, social support, bereavement, depression, hopelessness, mental disorders, and alcohol abuse are described. Physical illness, especially attendant on depression and feelings of hopelessness, also plays an important role. PMID- 1935195 TI - Suicide in the elderly: a report from India. AB - Those aged 60 years and older number 41 million, forming 7% of India's population. The suicide rate among the elderly is higher than the national rate. The data derived from the Government of India Statistics, from suicide prevention centers, suicide autopsies, geropsychiatric clinics, and survey studies indicate that suicide in the elderly is increasing. Depressive disease is the leading cause for suicide, followed by physical diseases and poverty. Family integration and social integration were found to be more important than "living in the family" or "living alone." Certain cultural suicide counters and the currently available prevention services are discussed. PMID- 1935196 TI - Suicide in the elderly: a report from Japan. AB - Immediately after World War II, the suicide rates for all age groups in Japan rose tremendously. Today we find much lower overall suicide rates. In studying suicide rates, one important trend attracts attention, namely that suicide rates are much higher in the elderly than in the younger age groups. Physical diseases seem to be of paramount importance in explaining suicidal behavior in the elderly. Developments in the 1960s and 70s may have led to material satisfaction, but simultaneously to spiritual poverty, loneliness, and depression, especially in males. PMID- 1935197 TI - Covariation of suicides and undetermined deaths among elderly persons: a methodological study. PMID- 1935199 TI - Rational suicide: how can we respond to a request for help? AB - For some persons who are facing terminal illness, severe permanent disability, or extreme old age, suicide may seem to be a rational choice. Suicide prevention services, however, do not provide for suicide as a sane, honorable choice in such circumstances. This paper identifies 17 specific considerations a mental-health professional may use to help such a person explore whether suicide would be rational or irrational. These considerations are formulated without antecedent bias towards prevention and without interpreting interest in suicide as evidence of depression or mental illness. Dying, severely disabled, and aged persons considering suicide on what seem to them to be rational grounds may thus trust and consult mental-health professionals about their plans. PMID- 1935198 TI - The prevention of suicide among older people in The Netherlands: interventions in community mental health care. AB - About one third of all suicides in the Netherlands are committed by elderly people. Yet, until recently no discernible initiatives have been taken to prevent suicide among the elderly. One of the possibilities that has not yet been considered is the use of mass media. In this article some thoughts are presented on the use of television and other media for communicating messages designed to identify depressive symptoms and to counter suicidal tendencies by mobilizing relatives and friends. Epidemiological findings on suicide among elderly persons in the Netherlands are presented, along with data on the role of the general practitioner and the mental health care system in suicide prevention. It is stressed that because of a number of unfortunate circumstances many depressed elderly people do not receive adequate treatment: Because they survived many major life events, their relatives wrongly consider them to be strong enough to cope with yet another major life event, loss or threatening condition. Relatives may think of depressed symptoms as a natural reaction, and may not consider these to be alarming. If they are alarmed, relatives may not know that depression is a treatable condition, or where they may be able to seek psychological assistance. Depressed elderly people might not be willing to share depressed feelings or thoughts concerning death and dying, or admit having suicidal ideation. Symptoms of depression may be confused with the normal aging process, both by the person him- or herself and by his or her relatives and friends. PMID- 1935200 TI - Suicide in the elderly: a frightful awareness. AB - Suicide in the elderly still remains a neglected topic. Our knowledge of basic characteristics of suicide in late life is still very limited. Physical disease, bereavement, isolation, and dependency in elderly people create the aura of rationality frequently and unrightfully attached to suicide in the elderly. Rationality may contribute to a final decision to end one's life. But rationality may also be a very misleading concept for a proper explanation of suicidal behavior. The discussion of the rationality of suicide in late life deserves good and thorough research. A political debate on this matter obscures the true reasons elderly have for committing suicide. Anxiety, fears, or threats of losing core aspects of one's identity are much more promising concepts for the study of late life suicide. The tendency to see many problematic situations as naturally tied to the aging process still exists and is pervasive. We hope that the material collected in this issue will stimulate better thinking and better research on late life suicide. PMID- 1935201 TI - Cell-cell communication: parathyroid hormone-like protein production by squamous carcinoma cells is modulated by fibroblasts. A possible mechanism in the development of humoral hypercalcemia of malignancy. PMID- 1935202 TI - Effect of UVASUN on porphyrin metabolism and P-450 isoenzymes in hexachlorobenzene-induced porphyric rats. PMID- 1935203 TI - The activity of erythrocyte porphobilinogen deaminase in familial and sporadic forms of porphyria cutanea tarda. PMID- 1935204 TI - Erythropoietic protoporphyria: clinical aspects with emphasis on the skin. PMID- 1935205 TI - Heme synthesis in protoporphyria. PMID- 1935206 TI - Point mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria (Gunther's disease). PMID- 1935207 TI - Ultrastructural aspects of the liver in erythrohepatic protoporphyria. PMID- 1935208 TI - Severe liver disease in protoporphyria. PMID- 1935209 TI - The role of diet in dermatitis herpetiformis. PMID- 1935210 TI - Role of elemental diet in dermatitis herpetiformis. PMID- 1935211 TI - Adverse reactions to food. PMID- 1935213 TI - Skin provocation test (SAFT) based on contact urticaria: a marker of dermal food allergy. PMID- 1935212 TI - Restriction of nickel intake in the treatment of nickel-sensitive patients. PMID- 1935214 TI - Analysis of delayed-type immunological responses to spices by patch testing. PMID- 1935216 TI - Glucagonoma syndrome. PMID- 1935217 TI - Thyroid and the skin. PMID- 1935215 TI - Effects of oral exposure to nickel or chromium on cutaneous sensitization. PMID- 1935218 TI - Normal and abnormal metabolism of lipoproteins. PMID- 1935219 TI - Macroscopic and microscopic structure of xanthomatous eruptions. PMID- 1935221 TI - Effects of retinoids on lipoprotein metabolism. PMID- 1935220 TI - New aspects of xanthomatosis and hyperlipoproteinemia. PMID- 1935222 TI - Porphyria cutanea tarda: clinical manifestations. PMID- 1935223 TI - Porphyria cutanea tarda: pathogenesis in relation to therapy. PMID- 1935224 TI - Porphyria cutanea tarda: erythrocyte uroporphyrinogen decarboxylase activity in 471 consecutive patients. PMID- 1935225 TI - Management of adrenal neoplasms. PMID- 1935226 TI - The Bunyaviridae and their genetics--an overview. PMID- 1935227 TI - Bunyavirus protein transport and assembly. PMID- 1935228 TI - Bunyaviridae: Pathogenesis. PMID- 1935229 TI - Bunyaviridae--natural history. AB - Obviously, the family Bunyaviridae is comprised of a large number of epidemiologically diverse viruses. They vary dramatically in their vector and vertebrate host relationships, geographic distributions, and epidemic potential in humans and animals. Public health practitioners, veterinarians, virologists, entomologists, biologists, ecologists, molecular biologists, and other scientists will all benefit from increased study and knowledge of this fascinating group of viruses. PMID- 1935230 TI - Virion structure. PMID- 1935232 TI - Safety of ethylenediamine tetraacetate in the treatment of lead poisoning in persons sensitive to ethylenediamine hydrochloride. PMID- 1935231 TI - Bunyaviridae genome structure and gene expression. PMID- 1935233 TI - A dermatologic diary. Portrait of a practice. PMID- 1935234 TI - Anthrax. PMID- 1935235 TI - Periorbital edema: an important physical finding in dermatomyositis. AB - Periorbital edema is frequently present in dermatomyositis and can be seen in the absence of other skin lesions. Sometimes, as in the two cases reported here, it can be the dominant physical sign. PMID- 1935236 TI - Cutaneous larva migrans due to Pelodera strongyloides. AB - A twenty-year-old landscape worker was evaluated for a widespread cutaneous eruption consisting of papules, pustules, and burrows. Cutaneous scrapings revealed live and dead larvae of a free-living soil nematode, Pelodera strongyloides. This is the third instance of human dermatitis due to this organism, and the first reported in an adult host. PMID- 1935237 TI - Chemotherapy-induced transverse ridging of the nails. AB - A case of Beau's lines secondary to combined chemotherapy for Hodgkin's disease is reported. These transverse nail depressions are interpreted as the result of a transient interruption of the nail matrix activity due to antimitotic drugs. Other causes of Beau's lines are reviewed. PMID- 1935238 TI - Extramedullary cutaneous plasmacytoma. AB - Neoplastic degeneration of plasma cells can show different clinical features, including multiple myeloma and plasma cell leukemia. Skin involvement is not rare in patients with multiple myeloma, and represents a poor prognosis. Appearance of a cutaneous plasmacytoma without the involvement of bone marrow is very rare. We describe a patient who had cutaneous plasmacytoma, with two solitary lesions of the oral cavity. The patient also showed a cerebral involvement, but no evidence of multiple myeloma, with normal-appearing bone marrow. PMID- 1935239 TI - Coexistent lepromatous leprosy and reactive perforating collagenosis. AB - The cases of two young men with coexistent lepromatous leprosy and reactive perforating collagenosis are reported. Although both patients' parents were consanguineous, experimental induction of Koebner's phenomenon by superficial scratching failed to produce the lesions of reactive perforating collagenosis. The lesions of reactive perforating collagenosis showed a satisfactory response to treatment with topical retinoic acid. PMID- 1935240 TI - Purpuric halos around hemangiomas in systemic amyloidosis. AB - A patient with systemic amyloidosis noted purpuric halos around cherry hemangiomas. This unique presentation of systemic amyloidosis has been reported once previously. A possible mechanism is the combination of amyloid deposition and excess plasminogen activator activity. PMID- 1935241 TI - Phytophotodermatitis due to figs. AB - Phytophotodermatitis is an acute skin reaction that may be easily confused with other causes of contact dermatitis. It is characterized by sunburn, blisters, and/or hyperpigmentation. The reaction takes place when certain plant substances known as psoralens, after being activated by ultraviolet light from the sun, come in contact with the skin. The condition is usually mild and self-limited but hyperpigmentation may persist for many weeks. Failure to recognize phytophotodermatitis in a child may lead to a mistaken diagnosis of child abuse. It is also important to be aware of perfumes and grocery products as causes of this phenomenon. PMID- 1935242 TI - The diagnostic dilemma of hyperpigmentation in patients with acquired immunodeficiency syndrome. PMID- 1935244 TI - What's good for the goose ... PMID- 1935243 TI - Zinc deficiency: report of three cases. AB - Acrodermatitis enteropathica has been reported as the skin disorder due to the congenital disturbance of zinc absorption in the intestine. We report on three patients with skin eruptions that resembled acrodermatitis enteropathica. Two were thought to have resulted from intravenous hyperalimentation and the other from artificial feeding. PMID- 1935245 TI - Patch testing for allergic reactions to metals in orthopedic implants. PMID- 1935246 TI - A dermatologic diary. Portrait of a practice. PMID- 1935247 TI - Concurrent infection with sporotrichosis and blastomycosis: an unusual case. AB - Two facial nodules and a pulmonary infiltrate occurred in a twenty-one-year-old man. Tissue cultures from one of the facial lesions showed both Sporothrix schenckii and Blastomyces dermatitidis. Cultures from lung biopsy tissue grew B. dermatitidis. This is the first known reported case of sporotrichosis and blastomycosis occurring concurrently in the same cutaneous lesion. PMID- 1935248 TI - Localized hyperkeratosis lenticularis perstans (Flegel's disease). AB - A case of hyperkeratosis lenticularis perstans involving only the back of a thirty-nine-year-old woman is reported. Histologic examination showed foci of compact and eosinophilic hyperkeratosis overlying a thinned stratum malpighii. In the underlying papillary dermis there was no evidence of inflammatory infiltrate. This case demonstrates that hyperkeratosis lenticularis perstans may appear as a localized disorder, and that the inflammation is not an essential pathogenic process in this disorder. PMID- 1935249 TI - Tegafur-induced acral hyperpigmentation. AB - Four patients with colorectal cancer treated with tegafur (a fluoropyrimidine structurally similar to 5-fluorouracil) noted a macular, spotted hyperpigmentation limited to the palms, soles, nails, and glans penis. Histopathologic examination disclosed epidermal basal hyperpigmentation with a lentiginous pattern. Mucocutaneous lesions resolved spontaneously two months after treatment was discontinued. This peculiar phenomenon seems to represent a previously unreported side effect of this cytotoxic drug. PMID- 1935251 TI - Late-onset nevus of Ota. AB - We report a patient with a type IB nevus of Ota whose lesion did not appear until she was thirty years old. To our knowledge, this represents the oldest age of a patient at clinical onset of nevus of Ota. The diagnosis, implications, and treatment of nevus of Ota are reviewed. PMID- 1935250 TI - Trichostasis spinulosa within an intradermal melanocytic nevus. AB - A thirty-six-year-old man presented with a melanocytic nevus on his left shoulder. The lesion was excised and histopathologic examination showed an intradermal nevus with several infundibular cysts among the nevus cells. These cysts showed a cyst wall with epidermoid keratinization and a lumen filled by many cross-sectioned hair shafts. These findings were consistent with a diagnosis of trichostasis spinulosa within an intradermal melanocytic nevus. We note the relationship between these two disorders in the same lesion. PMID- 1935252 TI - Cutaneous necrosis and pulse oximetry. AB - We report on two patients who developed cutaneous necrosis from the use of pulse oximetry monitoring. One developed digital skin necrosis from a finger sensor, while the other had a lesion of the pinna from an ear probe. Pulse oximetry monitoring is often used in the management of anesthetized and critically ill patients. Recognition of cutaneous necrosis with pulse oximetry may prevent unnecessary evaluation and prompt initiation of simple measures to protect against its occurrence. PMID- 1935253 TI - Superficial x-ray treatment of squamous cell carcinoma of the lower extremity. AB - Superficial x-ray therapy is an excellent modality for the treatment of squamous cell carcinomas of the lower extremity in the elderly. This technique is suitable for treating difficult squamous cell carcinomas and results in minimal morbidity and a short period of convalescence. PMID- 1935254 TI - Topical minoxidil in the treatment of androgenetic alopecia in women. AB - Twenty-eight women with mild to moderate androgenetic alopecia were randomly assigned to apply either 2 percent topical minoxidil or placebo (vehicle) to their involved scalp areas twice daily. At the end of thirty-two weeks, there was a statistically significant increase of nonvellus target area hairs in the minoxidil-treated versus the vehicle-treated group (p = 0.006). Investigator assessment of moderate regrowth showed better results in subjects who used 2 percent topical minoxidil solution than those who used vehicle (p = 0.007), although subjects discerned no difference between treatment groups. Two percent topical minoxidil appears to be effective in the treatment of female androgenetic alopecia. PMID- 1935255 TI - Role of C-heterochromatin in variation of nuclear DNA amount in the genus Chorthippus (Orthoptera, Acrididae). AB - Nuclear DNA amounts of nine species of grasshopper genus Chorthippus were determined in populations of southern Spain. There were significant differences between species, and between populations within certain species, for this character. Measurements of chromosomes in C-banded mitotic metaphase cells enabled the relative amounts of positively and negatively C-banded chromatin to be ascertained. This demonstrated that variations observed in nuclear DNA amount are due to changes in both types of chromatin but those in C-heterochromatin are much more important. PMID- 1935256 TI - Comparative analysis of autosomes in karyotypes from pig and rabbit using RBG banding and in situ hybridization. AB - The chromosomal location of the porcine gene for glucose phosphate isomerase (GPI) was previously mapped to 6p 12----6q21 in the pig karyotype. The replication patterns and morphology of this chromosome are very similar to those of chromosome 14 in the rabbit karyotype. With combined in situ hybridization and RBG-band induction it was demonstrated that the porcine GPI-probe hybridized most frequently to 14p11----14q12 in the rabbit karyotype, indicating a close relationship between morphology, replication pattern and gene location. PMID- 1935257 TI - Cytogenetics of fleas (Siphonaptera: Pulicidae). 1. Rat fleas of the genus Xenopsylla. AB - Five populations of Xenopsylla cheopis exhibit a chromosome complement of 2n = 17, X1X2Y (male), and 2n = 18, X1X1X2X2 (female). A detailed analysis of populations of X. astia from Bombay and Trivandrum led to the identification of two distinct cytotypes which hybridisation studies indicated were sibling species. These are referred to as X. astia with a diploid chromosome number of 2n = 18, X1X2X3Y (male), and 2n = 20, X1X1X2X2X3X3 (female) and X. prasadii with 2n = 10, X1X2Y1Y2 (male), and 2n = 10 X1X1X2X2 (female). It is proposed that X. prasadii is derived from X. astia through translocation/fusion events since the average total chromosome lengths are remarkably similar in all three species. PMID- 1935258 TI - Interpretation of intraluminal manometric measurements in terms of swallowing mechanics. AB - A unified discussion of the mechanics of the swallowing process, and its interpretation through manometric measurements of intraluminal pressure, are presented in this paper. The goals of the discussions are to provide the reader with basic knowledge of pharyngeal, esophageal, and sphincter mechanics; to relate the mechanical processes to intraluminal pressure recordings; and to clarify the relationship between intraluminal pressure and esophageal muscle contractile behavior. The esophageal phase of bolus transport, in particular, is discussed in some detail due to the relatively simple geometry and the straightforward description of peristalsis and muscle mechanics in this region. Several important issues are emphasized in the discussion. For example, pressure variation within a static bolus is fundamentally different from that within a moving bolus. Manometric recordings must be interpreted accordingly. The importance of differentiating between "hydrodynamic pressure," which is pressure measured within a fluid bolus, and "contact pressure," which is the direct squeeze of the luminal wall on the manometric port in a region devoid of bolus fluid, is discussed in some detail. We argue that pressure "amplitude" does not, in principle, give any indication of the forces required to drive the fluid bolus forward. What should be sought is the variation of intrabolus pressure relative to the contact pressure, particularly during periods in which the contractile segment fails to obliterate the esophageal lumen. Examples of intraluminal pressure recording in the esophagus, using manometry and mathematical models, are presented to demonstrate both the possibilities and the difficulties of interpreting manometric recordings in the absence of concurrent radiographic imaging. We discover that in regions of nearly complete luminal closure, the pressure signature and bolus geometry are strongly coupled during peristaltic transport, providing the possibility that in these regions quantitative measures of muscle performance might be developed without the need for radiographic imaging. On the other hand, the ambiguity in the interpretation of manometric recordings that often accompanies dysphagic conditions suggests that as more sophisticated interpretations are sought, manometry concurrent with radiography will play a more prominent role in patient evaluation. PMID- 1935259 TI - Case report: aspiration from delayed radiation fibrosis of the neck. AB - An unusual case of delayed severe fibrosis of the soft tissues of the neck following radiation therapy for squamous cell carcinoma of the oropharynx resulting in dysphagia and recurrent aspiration is reported. The patient's case history, radiographic findings, and speech-language pathologic evaluation are presented. PMID- 1935260 TI - Dysphagia. Management: general principles and guidelines. PMID- 1935263 TI - Managing dysphagia in mentally retarded adults. AB - Mentally retarded adults with dysphagia are a chronically disabled population with high incidence of co-occurring gastrointestinal and respiratory disorders. Their ability to achieve and maintain optimal functional adequacy of swallow is dependent on medical and nutritional management of the disorder, as well as on improving the swallow itself. This paper presents a dysphagia management protocol for this population, which includes screening to identify at risk individuals, diagnostic evaluation of dysphagia, daily management to promote optimal mealtime function, and dysphagia therapy to improve underlying neuromotor competency and eating skills. PMID- 1935262 TI - Surgical solutions for esophageal dysphagia. PMID- 1935261 TI - Surgical approaches to aspiration. AB - Impaired laryngeal protective function can result in intractable aspiration. Surgery to separate the upper digestive tract from the respiratory tract is often necessary in cases of intractable aspiration to prevent recurrent bronchopulmonary contamination and resultant complications, including death. The common surgical techniques for the prevention of intractable aspiration are presented. The results of each procedure for aspiration prevention and reversibility are compared. The advantages and disadvantages of each surgical technique are discussed. PMID- 1935264 TI - Use of the electroglottograph for measurement of temporal aspects of the swallow: preliminary observations. AB - The electroglottograph (EGG) is a non-invasive, electrical impedance device that was developed for observing vocal fold contract during phonation. After a thorough study of the frequency response characteristics of the EGG, we found that the EGG output can be used to identify maximum laryngeal displacement and the duration of laryngeal movement during swallowing. With a small intranasal pressure transducer placed beneath the velum and the EGG electrodes placed externally on the thyroid cartilage, additional information on the temporal aspects of the swallow can be measured. The EGG has direct clinical application when teaching such techniques as the safe swallow and Mendelsohn maneuver and it is useful as a research technique when using repeated measures designed to study the swallow reflex. PMID- 1935265 TI - Using ventilators for speaking and swallowing. AB - An inflated cuff, although commonly thought to be required for the ventilator dependent patient with a tracheostomy cannula, precludes speaking and has adverse implications for swallowing. Clinical trials with five ventilator-dependent, cognitively intact individuals with glottic control document that a deflated cuff is compatible with ventilation, preserves oral communication, and restores safe alimentation by mouth. PMID- 1935266 TI - Clinical diagnosis of acute pulmonary embolism. When should a V/Q scan be ordered? PMID- 1935267 TI - Dyspnea: time to find the facts. PMID- 1935268 TI - Pseudosepsis syndrome, multiple-system organ failure, and chronic salicylate intoxication. Inhibition of regulatory eicosanoids? PMID- 1935269 TI - Aerosolized pentamidine prophylaxis. PMID- 1935270 TI - When life support is futile. PMID- 1935271 TI - Endobronchial suture. A foreign body causing chronic cough. AB - Although rarely considered in series of lower airway foreign bodies, endobronchial sutures can cause chronic cough or hemoptysis years after thoracic surgery. Eight endobronchial sutures were found in six patients who had undergone surgery four to 30 years prior to admission. Symptoms began two to 25 years after surgery and lasted from two to six years prior to diagnosis. Cough had been attributed to chronic bronchitis or bronchiectasis in five patients and to tracheal narrowing secondary to surgical repair of tracheomalacia in the sixth. Bronchoscopy was diagnostic in all cases. Suture removal was performed with either forceps or endoscopic suture scissors to cut the suture followed by extraction with forceps. Symptoms resolved within three days and granulation tissue by two to four weeks after suture removal. This series suggests that endobronchial suture should be considered in patients with a history (even remote) of previous thoracic surgery who present with chronic, persistent cough unresponsive to specific therapy for any underlying pulmonary disease. PMID- 1935272 TI - Mast cells in bronchoalveolar lavage fluid and in transbronchial biopsy specimens of patients with farmer's lung disease. AB - Recently, an increased number of mast cells have been reported in bronchoalveolar lavage fluid (BAL) of patients with farmer's lung disease. Some authors pointed out the pathogenetic importance of mast cells in farmer's lung on the basis of their correlation with the activity of the disease, with the BAL lymphocyte counts, and with the markers of lung fibrosis. To determine whether BAL reflects the histologic aspects of the lung histologic features in patients with farmer's lung disease, mast cells recovered from lavage fluid were compared with tissue sections from transbronchial lung biopsies in 15 patients. Mast cell counts in BAL and lung biopsy specimens were significantly correlated (r = 0.88; p less than 0.01), while no other correlations between BAL inflammatory cells and tissue mast cells were found. In lung tissue, there were four times the increased number of mast cells in respect to the control group (84.4 +/- 28.8 vs 20.4 +/- 13.4 mast cells per square millimeter); 83.2 percent of mast cells were found in the alveolar septa, 14.9 percent within alveoli, 0.7 percent among alveolar lining cells, and 1 percent along blood vessels. No mast cells were located within alveoli in controls. In BAL, only lymphocyte and mast cell counts (56.4 +/- 18.6 percent, p less than 0.001; 3.9 +/- 1.5 5 percent, p less than 0.001, respectively) were significantly increased. Our data suggest that in farmer's lung disease, BAL correctly samples the alveolitis. Mast cells, such as lymphocytes, seem to be primary inflammatory cells involved at the site of the disease activity. PMID- 1935274 TI - Urine pentamidine as an indicator of lung pentamidine in patients receiving aerosol therapy. AB - To determine if urine pentamidine was reflective of lung pentamidine, we compared levels of the drug in bronchoalveolar lavage fluid and simultaneously obtained urine. Thirty-one patients who were receiving aerosolized pentamidine either as treatment or as prophylaxis underwent BAL and submitted urine samples for pentamidine analysis. Pentamidine was analyzed in both phases of BAL fluid (supernatant and cell pellet) and in urine using high performance liquid chromatography. Urine results were normalized for creatinine. Patients were categorized as prophylaxis failures (active Pneumocystis carinii pneumonia on prophylaxis), electives (free from PCP on prophylaxis), treatment (daily AP in treatment doses for active PCP, or miscellaneous (single dose of AP). Levels in BAL fluid and urine varied widely over several orders of magnitude. However, for all patients, we found a highly significant relationship between BAL supernatant and urine (r = 0.97, p less than 0.0001). No statistical differences were found when comparing levels of pentamidine between failures and electives; however, the number of failures was small. We conclude that urine pentamidine is related to lung pentamidine and can be used as a clinical indicator in patients receiving aerosolized therapy. PMID- 1935273 TI - Detection of massive pulmonary embolus-in-transit by transesophageal echocardiography. AB - Pulmonary embolus-in-transit represents an important cause of morbidity and mortality in the critically ill patient. Unexplained shock and acute pulmonary hypertension were evaluated with echocardiography. Standard transthoracic echocardiography failed to identify a large embolism-in-transit that was easily visualized by transesophageal imaging. A review of the literature involving emboli-in-transit suggests that early intervention in these patients may be beneficial. PMID- 1935275 TI - Pneumothorax with Pneumocystis carinii pneumonia in AIDS. Incidence and clinical characteristics. AB - A retrospective review of the charts of patients with the acquired immunodeficiency syndrome (AIDS) was performed at three university-affiliated teaching hospitals in Denver between May 1982 and April 1987. Patients were evaluated for the presence or absence of Pneumocystis carinii pneumonia (PCP) and for the occurrence of pneumothorax at any time during their clinical course. The incidence of pneumothorax in AIDS patients with PCP was 9.0 percent (8/89), compared with 0 percent (0/45) in AIDS patients without PCP (p less than 0.03). All of the pneumothoraces resolved, most without chest tube placement. This study suggests that in patients with AIDS, PCP is associated with an increased incidence of pneumothorax, while AIDS patients without PCP are not at increased risk for the development of pneumothorax. PMID- 1935276 TI - The effect of body posture on exercise- and hyperventilation-induced asthma. AB - Recent studies have shown that swimming is of relatively low asthmogenicity, even under conditions of high respiratory heat (and/or water) loss (RHL). It has been suggested that the horizontal body position may contribute to swimming's low asthmogenicity. We studied the effects of upright and prone body postures on pulmonary function following exercise (EIA) and after nonexercise hyperventilation (HIA). Twelve asthmatic boys (aged 12 to 16 years) underwent two 8-min exercise sessions of shoulder flexion-extension and two 8-min isocapnic hyperventilation treatments, in a counterbalanced order, either while lying prone or standing upright. All tests were carried out in a climatic chamber at 10 +/- 1 degree C and 31 +/- 2 percent relative humidity. Minute ventilation (VE) was kept constant at a predetermined individual level during all treatments. No differences were observed in pulmonary functions between the prone and upright postures following either exercise (FEV1 = -20.5 +/- 18.7 percent vs -22.2 +/- 18.7 percent, respectively) or hyperventilation (FEV1 = -29.6 +/- 19.0 percent vs -29.7 +/- 20.2 percent). We conclude that body posture on land has no meaningful effect on the severity of bronchoconstriction in asthmatic children; however, in view of some conceivable physiologic benefits of the prone position in water, an interactive effect on swimming-induced asthma (SIA) of body posture and water immersion cannot be ruled out. PMID- 1935277 TI - The effects of influenza virus infection on FEV1 in asthmatic children. The time course study. AB - To study the time-course of influenza-induced asthma, we retrospectively examined FEV1 from five days before to ten days after the onset of illness in 20 asthmatic children aged 8 to 12 years with tolerable respiratory symptoms. Influenza infection was confirmed by a rise at least fourfold in serum complement fixation titers. Fifteen of 20 patients had decrease in FEV1 more than 20 percent from baseline during the acute stage. FEV1 began to decrease with the onset of illness in the 15 patients with the exception of one whose FEV1 decreased during the incubation period. It continuously decreased on the second day, when mean (+/- SD) decrease in FEV1 became maximum, 30.3 +/- 10.9 percent. It began to improve on the third day, and returned within 10 percent difference on the seventh to tenth day. We conclude that influenza-induced asthma may continuously deteriorate during the first two days of illness and may require at least seven days for recovery. PMID- 1935278 TI - Diagnosis of tuberculous pleural effusion by the detection of tuberculostearic acid in pleural aspirates. AB - Detection of TBSA was attempted in pleural aspirates of 74 patients with tuberculous and 44 patients with nontuberculous pleural effusion by gas chromatography/mass spectrometry with selected ion monitoring. The results were disappointing with a test sensitivity of 67.6 percent and a specificity of 52.3 percent. In contrast, histologic examination of pleural biopsies gave a diagnostic sensitivity of 71.0 percent. Pleural biopsy remains a better investigational procedure for the diagnosis of tuberculous pleural effusion. PMID- 1935279 TI - The relationship between pleural fluid findings and the development of pleural thickening in patients with pleural tuberculosis. AB - The objective of the study was to determine if residual pleural thickening after treatment for pleural tuberculosis could be predicted from the pleural fluid findings at the time of the initial thoracentesis. Forty-four patients initially diagnosed as having pleural tuberculosis between January 1986 and January 1988 were separated into two groups: the 23 patients in group 1 had residual pleural disease, while the 21 patients in group 2 had no residual pleural disease after treatment for their pleural tuberculosis was completed. The clinical characteristics of the two different groups did not differ significantly, but the patients in group 1 tended to be a little sicker in that the duration of their symptoms was longer, their hemoglobin values were lower, and weight loss and cough were more frequent. There were no significant differences in the pleural fluid findings in the two different groups. The mean pleural fluid protein level was 5.40 +/- 0.58 g/dl for group 1 and 5.17 +/- 0.80 g/dl for group 2, while the mean pleural fluid glucose level was 78.6 +/- 19.5 mg/dl for group 1 and 79.5 +/- 20.1 mg/dl for group 2. The mean pleural fluid lactate dehydrogenase (LDH) level in group 1 was 593 +/- 498 IU/L, while the mean level for group 2 was 491 +/- 198 IU/L. The presence of residual pleural thickening was not related to the chemotherapeutic regimen or the performance of a therapeutic thoracentesis. From this study we conclude that approximately 50 percent of patients with pleural tuberculosis will have residual pleural thickening when their therapy is completed, but that one cannot predict which patients will have residual pleural thickening from either their clinical characteristics or their pleural fluid findings. PMID- 1935280 TI - Primary pulmonary hypertension in HIV infection. AB - A prospective evaluation of 74 human immunodeficiency virus (HIV)-infected patients with cardiopulmonary complaints revealed six patients (8.1 percent) with pulmonary hypertension with elevated right ventricular systolic over right atrial pressure of 58 +/- 8 mm Hg (range, 49 to 66 mm Hg), as documented by Doppler echocardiography. A thromboembolic cause was excluded by normal lung perfusion scans. Electrocardiographic and roentgenographic features of pulmonary hypertension were present in five patients. Two patients died three and nine months after diagnosis of pulmonary hypertension. Autopsy revealed plexogenic pulmonary arteriopathy in both. The observation of six patients with primary pulmonary hypertension (PPH) in a cohort of 1,200 HIV-infected subjects corresponding to an incidence of 0.5 percent is striking and suggests a possible association of PPH with HIV infection. PMID- 1935281 TI - Human alveolar macrophages of anergic patients with lung cancer lack the responsiveness to recombinant interferon gamma. AB - We studied the effect of recombinant interferon gamma (rIFN-gamma) on the phagocytic and bactericidal actions in human alveolar macrophages (AM) of patients with pulmonary tuberculosis and lung cancer. Treatment with 100 or 1,000 U/ml of rIFN-gamma for 24 hours resulted in an increased percentage of AM ingesting bacillus Calmette-Guerin (BCG) and an increased number of ingested BCG in individual AM in tuberculin-positive patients with lung cancer and pulmonary tuberculosis. The rIFN-gamma treatment also showed increased killing activity of AM in tuberculin-positive patients. However, rIFN-gamma treatment of AM in tuberculin-negative anergic patients with lung cancer did not induce the increase of phagocytic and killing activities against BCG. These results suggest that responsiveness and activation of AM to rIFN-gamma are inhibited in the anergic environment. PMID- 1935282 TI - Measurement of sleep-related breathing disturbances in epidemiologic studies. Assessment of the validity and reproducibility of a portable monitoring device. AB - The feasibility and reliability of measuring sleep-related breathing disorders with a portable monitor (PM) were assessed in a heterogeneous population, consisting of 31 patients recruited from a sleep laboratory and pulmonary disease clinic, 16 participants in a genetic-epidemiologic study of sleep apnea, and four volunteers with no specific sleep complaints. The validity of measurements made by the PM was assessed with comparisons of respiratory parameters made with the PM to those determined with in-hospital polysomnography (PSG) (25 studies). Reproducibility was assessed in 29 subjects who underwent in-home monitoring on two occasions. There was a high level of agreement between the number of respiratory events (apneas or hypopneas) per hour of estimated sleep (respiratory disturbance index, RDI) recorded with the PM and PSG and log-transformed (r = 0.96). Using a RDI of greater than or equal to 10 to define "abnormality," 20 of the 21 subjects who would have been classified as abnormal with PSG were classified similarly with use of the PM. A similar high level of agreement was demonstrated for the log-transformed RDI determined with replicate in-home studies (r = 0.94). No evidence of a "first-night effect" for the RDI was suggested in studies performed with the PM; ie, RDI was 18.4 +/- 27.7 and 17.4 +/ 25.7 (mean +/- SD) for first and second night studies, respectively (p = 0.21). A second compared with an initial study with the PM would have resulted in reclassification of abnormality based on an RDI of greater than or equal to 10 in one subject. These findings suggest that measurement of the RDI with in-home monitoring provides a valid and highly reproducible index for assessment of sleep related respiratory disturbances for use in epidemiologic studies of general populations. PMID- 1935283 TI - Transcutaneous oxygen saturation and carbon dioxide tension during meals in patients with chronic obstructive pulmonary disease. AB - The effect on transcutaneous SaO2 and transcutaneous carbon dioxide tension (PtCO2) of eating was assessed in 44 patients with severe COPD (FEV1 less than 50 percent). The SaO2, PtCO2, and heart rate (HR) were measured every minute before, during, and until 30 minutes after a standardized meal (445 kcal) was consumed. All patients were measured twice on the same day, while eating a meal with high (80 percent) and low (28 percent) carbohydrate content, respectively. The mean meal desaturation (delta SaO2) was less than 1 percent in normoxemic patients but was -3.2 +/- 0.7 percent (p less than 0.001) in hypoxemic (PaO2 less than 7.3 kPa) patients. Significant differences between hypoxemic patients with a delta SaO2 greater than 4 percent and less than or equal to 4 percent, respectively, were found in FEV1 (16 +/- 3 percent and 29 +/- 8 percent; p less than 0.001), respiratory muscle strength (3.9 +/- 1.2 kPa and 5.9 +/- 1.2 kPa; p less than 0.01), HR (112 +/- 12 beats per minute and 90 +/- 18 beats per minute; p less than 0.001), body weight (54.9 +/- 7.5 kg and 74.7 +/- 10.4 kg; p less than 0.001), and fat-free mass (42.0 +/- 6.6 kg and 52.6 +/- 5.8 kg; p less than 0.005) but not in baseline SaO2 and PtCO2. The decrease in SaO2 and the increase in HR were less during the carbohydrate-rich meal. No significant fluctuations in PtCO2 were found after either meal. Meal-related oxygen desaturation cannot explain weight loss in normoxemic patients with COPD but may contribute to a limited dietary intake in a subgroup of hypoxemic patients exhibiting marked oxygen desaturation during meals. A single carbohydrate-rich meal does not have an immediate impact on PtCO2 in stable COPD. PMID- 1935284 TI - Chronic dyspnea unexplained by history, physical examination, chest roentgenogram, and spirometry. Analysis of a seven-year experience. AB - The purpose of this article is to describe the spectrum and frequency of diseases presenting as unexplained dyspnea and to develop a logical diagnostic approach to such patients. Seventy-two consecutive physician-referred patients had dyspnea greater than one-month duration unexplained by the initial history, physical examination, chest roentgenogram, and spirometry. Patients underwent a standard diagnostic evaluation. A definite cause for dyspnea was recognized in 58 patients, and no answer was found in 14. Twenty-two diseases were recognized in the patient group. Dyspnea was due to pulmonary disease in 26 (36 percent) patients, cardiac disease in ten (14 percent) patients, hyperventilation in 14 (19 percent) patients, and only 3 patients had extrathoracic disease causing dyspnea. Age younger than 40 years, intermittent dyspnea, and normal alveolar arterial oxygen pressure difference (P[A-a]O2) at rest breathing room air was strongly predictive of bronchial hyperreactivity or hyperventilation. No patient diagnosed as having disease of the lung parenchyma or vasculature had a P(A-a)O2 less than or equal to 20 mm Hg. The differential diagnosis to explain dyspnea in patients with nondirective histories, normal findings from physical examinations, normal chest roentgenograms, and normal spirograms is extensive. The patient's age and measurement of gas exchange at rest help to formulate a diagnostic approach. PMID- 1935286 TI - Variable radiomorphologic data of high altitude pulmonary edema. Features from 60 patients. AB - The purpose of the study was to collect radiomorphologic data of a large population of subjects with high altitude pulmonary edema. A blinded retrospective analysis of 60 patients severe enough to warrant hospital admission is reported. Immediately after rescue to low altitude, the severity of HAPE was graded using a quadrant-based scoring system (0-4 each quadrant). Its distribution and the morphologic features were noted. HAPE was more severe in the base, and specifically, the right lower quadrant, as compared to the other quadrants. It was often located both centrally and peripherally (60 percent) and in 92 percent was characterized by air space disease of homogeneous (n = 40) rather than patchy distribution (n = 15). In recurrent HAPE (n = 13), radiomorphologic data were as variable as among different HAPE patients. We conclude that HAPE does not have one common radiomorphologic condition. Based on the literature, earlier experience, and follow-up observations, we hypothesize that it may start patchy and peripheral, supporting the concept of uneven vasoconstriction with overperfusion and/or permeability leak. Later on, such as in the severe cases studied, it becomes homogeneous. Recurrent episodes generally do not show an identical distribution of HAPE, suggesting that structural abnormalities are not involved in the pathogenesis of HAPE. PMID- 1935285 TI - Comparison of a hand-held nebulizer with a metered dose inhaler-spacer combination in acute obstructive pulmonary disease. AB - This study compared the effect of "standard" dose metaproterenol delivered by hand-held nebulizer (HHN) with two puffs of metaproterenol delivered by a metered dose inhaler (MDI) via a spacer (InspirEase) (MDI-spacer). Seventeen patients with an acute exacerbation of obstructive pulmonary disease were studied. Each patient received both MDI-spacer and HHN. Alternate patients were randomized to either MDI-spacer or HHN as initial treatment. Each subject was tested four different times: before and 30 minutes after the initial aerosol delivery technique, and before and 30 minutes after the alternate aerosol delivery technique. Testing consisted of spirometry, lung auscultation, and measurement of vital signs. The interval between treatments for all subjects was 2.96 +/- 0.27 hours (mean +/- SEM) and was not different for subjects who received therapy via MDI-spacer first or HHN first. The patient population studied demonstrated severe airways obstruction (baseline FEV1 33.3 percent predicted +/- 4.9 percent). There was a statistically significant improvement in FVC and FEV1 after metaproterenol delivered by HHN, but not after MDI-spacer. Metaproterenol treatment with HHN resulted in a greater improvement in FEV1 (p less than .05) than MDI-spacer when the data were reported as absolute improvement (0.19 +/- 0.05 L for HHN) vs (0.06 +/- 0.03 L for MDI-spacer) or reported as percent change (23.2 +/- 6.6 percent for HHN) vs (9.5 +/- 3.4 percent for MDI-spacer). Asthmatic patients exhibited a significantly greater (p less than 0.05) improvement in FEV1 after HHN (23.4 +/- 4.7 percent change) than after MDI-spacer (6.6 +/- 4.5 percent change). Patients with chronic obstructive pulmonary disease (COPD) exhibited a greater improvement in FVC (p less than 0.05) after HHN (25.2 +/- 6.7 percent change) than after MDI spacer (5.8 +/- 4.7 percent change). We conclude that the "standard" dosage of metaproterenol delivered by HHN results in greater spirometric improvement in patients with acute obstructive pulmonary disease than the conventional dosage of metaproterenol delivered by MDI-spacer. It is likely that this reflects the fact that the recommended dose of metaproterenol delivered by MDI is too low and should be increased. PMID- 1935287 TI - Does the magnitude of mitral regurgitation determine hemodynamic response to vasodilation in chronic congestive heart failure? AB - Although it is usually assumed that direct-acting vasodilators improve cardiac function in patients with congestive heart failure (CHF) by altering left ventricular preload and afterload, several studies have suggested that most of the benefit occurs as a result of a reduction in associated mitral regurgitation (MR), which is present in the majority of patients with severe CHF. To test his hypothesis, the hemodynamic response to oral hydralazine was examined in CHF patients with competent mitral prostheses (group 1) and patients with CHF due to severe MR and left ventricular dysfunction (group 2). Both groups demonstrated significant increases in cardiac, stroke volume, and stroke work indices, although these were greater in group 2. Only group 2 experienced a significant reduction in left ventricular filling pressure. Thus, the presence of MR is not essential for hemodynamic improvement but is associated with significantly greater responses. PMID- 1935288 TI - Surgical correction of posttraumatic VSD via the right atrium. AB - We report the cases of four patients seen with ventricular septal defects (VSDs) resulting from penetrating chest trauma; initial surgical management was via left thoracotomy and comprised relief of tamponade and suture of the surface cardiac wound. A VSD was suspected in all four patients postoperatively on the basis of a holosystolic murmur as confirmed with two-dimensional echo and angiography. Elective surgical repair was undertaken on cardiopulmonary bypass with bicaval cannulation and cardioplegic arrest. The interventricular septum was approached through the right atrium (no attempt was made to free the anterior surface of the right ventricle from adhesions). Three defects were closed directly and one was closed with a pericardial patch. The surgical correction of posttraumatic VSD from a penetrating injury can be safely and effectively achieved via a right atrial approach. PMID- 1935289 TI - Hypoxia and cyanosis in alpha-1-antitrypsin deficiency. Cirrhosis as an unusual etiologic factor. AB - A patient with type PiZZ alpha-1-antitrypsin deficiency was found to have severe hypoxia despite normal pulmonary function testing and a normal chest radiograph. A nuclear medicine ventilation-perfusion study revealed a right-to-left shunt. Computed tomography showed minimal bleb formation, no diffuse changes, and hepatic changes of cirrhosis with portal hypertension. No nodular pulmonary masses or enlarged peripheral pulmonary vessels were found. The diagnosis of diffuse intrapulmonic arteriovenous shunts ("pulmonary spiders of cirrhosis") was suggested and then confirmed with a dynamic radionuclide flow study. PMID- 1935290 TI - Ultrasound-guided pleural biopsy with Tru-Cut needle. AB - We conducted a study of ultrasound (US)-guided pleural biopsy with a Tru-Cut needle and made a comparison with the results of a traditional pleural biopsy with an Abrams needle. A total of 49 patients with unilateral pleural effusion were included in this study. Twenty-four patients underwent a traditional pleural biopsy with an Abrams needle, and 25 patients underwent a US-guided pleural biopsy with a Tru-Cut needle. The age, sex, and underlying diseases in both groups were compatible. The amount of effusion was much less in the Tru-Cut group. In the patients who underwent the US-guided pleural biopsy with a Tru-Cut needle, the diagnostic sensitivity in pleural tuberculosis was 86 percent (6/7) and in pleural neoplasia it was 70 percent (7/10). In the patients who underwent traditional pleural biopsy with an Abrams needle, the diagnostic sensitivity in pleural tuberculosis was 20 percent (2/10) and in pleural neoplasia it was 44 percent (4/9). The result of US-guided pleural biopsy with a Tru-Cut needle was better than that of pleural biopsy with an Abrams needle, especially in pleural tuberculosis. No complication was found in the Tru-Cut group, but breakage and dislodgment of the tip of an Abrams needle occurred in one patient. The higher diagnostic yield in the Tru-Cut group may be attributed to the US guidance that can delineate the focal pleural abnormalities for biopsy. In conclusion, US guided pleural biopsy by using a Tru-Cut needle was simple, safe, and well tolerated. It was particularly useful for patients with pleural tumor, thickened pleura, small amounts of pleural effusion, or loculated pleural effusion. PMID- 1935291 TI - Voluntary hyperventilation in obesity hypoventilation. AB - Arterial blood gas analysis was performed before and after 60 to 90 s of voluntary hyperventilation in 27 consecutive patients with occlusive sleep apnea syndrome (OSA) and daytime hypercapnia. The percentage of fall in PaCO2 from baseline was examined in relationship to age, body mass index, sleep-disordered breathing indices, and pulmonary function variables. In 14 subjects without airflow obstruction, only one individual could not voluntarily hyperventilate into the normal range, whereas 6 of 13 subjects with airflow obstruction could not hyperventilate to eucapnia. The average percentage of fall in PaCO2 was 16 mm Hg (SEM = 1.3 mm Hg). The percentage of fall in PaCO2 correlated significantly with FEV1/FVC ratio (r = 0.47, p = 0.01) and with FEV1 (r = 0.5, p = 0.008). Although the baseline PaCO2 did not correlate with FEV1, the posthyperventilation PaCO2 did (r = 0.54, p = 0.003). Voluntary hyperventilation studies herein suggest a predominant role for impairment of ventilatory control in the maintenance of hypercapnia in OSA since a fall of PaCO2 into the normal range can usually be obtained. The correlation between the percentage of fall in PaCO2 and spirometric measures of respiratory mechanics, as well as the inability of some subjects to normalize the PaCO2 voluntarily suggests an added role for respiratory mechanical impairment in obesity hypoventilation. PMID- 1935292 TI - Extreme variability in aerosol output of the DeVilbiss 646 jet nebulizer. AB - Ten new jet nebulizers (DeVilbiss 646) were studied to determine their consistency of output. Each nebulizer, containing 2 ml of saline solution, was run for 1 min in triplicate at four different straw (capillary tube) positions, keeping all other variables constant. Total output in milliliters per minute and volume of aerosol in the respirable range (1.0 to 5.0 microns) were measured. There was significant variability in output and volume of output in the respirable range (VORR) for every nebulizer at each of the tested straw positions (p less than 0.0001). Irregularities in manufacture of the bowl and straw appear to be responsible for this significant variability. In summary, there is considerable intranebulizer and internebulizer variability that could influence both patient care and medical use for diagnostic purposes. PMID- 1935293 TI - Diagnostic approach to Pneumocystis carinii pneumonia in the setting of prophylactic aerosolized pentamidine. AB - Recurrent Pneumocystis carinii pneumonia is common in patients with the acquired immunodeficiency syndrome who receive prophylaxis with aerosolized pentamidine. In this setting, the number of organisms is reduced and the clinical presentation may be altered. These observations have led to doubts regarding the use of induced sputum to diagnose PCP in patients receiving prophylactic AP. To determine if the examination of induced sputum is useful for patients receiving prophylactic AP, we examined our results over a 12-month period. We also examined several clinical criteria to ascertain if they could predict the likelihood of a positive induced sputum. As assessed by P(A-a)O2, need for admission and mortality, patients receiving AP presented with less severe disease than those not receiving AP. Twelve of 19 (63 percent) patients who developed PCP while receiving prophylactic AP were diagnosed by induced sputum. Induced sputum was positive for 35 of 55 (64 percent) patients who developed PCP and had not been receiving AP. However, there were no clinical characteristics which predicted a positive induced sputum. We conclude that induced sputum is an effective method for diagnosing PCP in patients receiving prophylactic AP. PMID- 1935294 TI - The effects of postural drainage and positive expiratory pressure physiotherapy on tracheobronchial clearance in cystic fibrosis. AB - We studied the effects of two chest physiotherapy regimens on whole lung and regional tracheobronchial clearance (TBC) in ten patients with cystic fibrosis. The regimens were given on two separate days and consisted of 20 min of (1) postural drainage and the forced expiration technique (PD + FET), and (2) positive expiratory pressure (PEP-mask) and FET (PEP + FET). A third day served as control. The study days were randomized. Each day, the clearance of lung radioactivity was measured for 3 h by gamma camera. The number of spontaneous coughs was recorded and the sputum expectorated was sampled. We found that both PD + FET and PEP + FET improved whole lung TBC at 30 minutes and 1 h four or fivefold (p less than 0.01) compared with control, whereas at 2 h and 3 h only the improvement following PEP + FET (approximately 1.4 times) was significant (p less than 0.05). There was no significant difference in whole lung or regional TBC between the PD + FET and PEP + FET treatments. The correlations between TBC and the radioactivity content in sputum expectorated (rs2 = 0.76) and between TBC and numbers of coughs (rs2 = 0.65) were better than between TBC and the weight of sputum expectorated (Rs = 0.39). We conclude that PD or PEP when combined with FET have similar effects on short-term whole lung and regional TBC in patients with cystic fibrosis. Evaluation of TBC during chest physiotherapy when only based on the weight of sputum expectorated seems inadequate. PMID- 1935295 TI - Digitized cardiac potentials recorded with CR leads. Development of a portable electrocardiograph. AB - This report describes the advantages of recording cardiac potentials in digital rather than in analog form and of using statistical methods that compare a patient's measurements with values measured in a normal population. In this study, expansion of the time axis in digitized electrocardiograms was used to accurately determine the moments when the Q, R, and S waves began and ended. This work is part of a plan to develop a portable electrocardiograph that could be available to physicians at all times. The immediate availability of such an instrument could shorten the time required to reach a diagnosis and institute treatment in cardiac emergencies occurring where diagnostic facilities are unavailable. PMID- 1935296 TI - Pressure support ventilation with a simplified ventilatory support system administered with a nasal mask in patients with respiratory failure. AB - Thirty-one consecutive patients with respiratory failure in whom treatment with intubation and mechanical ventilation was being strongly considered received alternative ventilatory support by means of a BiPAP ventilatory support system and nasal mask. Laboratory measurements and physical findings were documented before and 1 h after initiation of support. This support improved patient comfort, slowed respiratory rate, and improved oxygenation. Support lasted from 2 h to six days. Seventy-six percent (22/29) of patients recovered from this episode of respiratory failure, avoiding alternative mechanical ventilatory support. There were no complications associated with aspiration, gastric distention, or acute separation from support. PMID- 1935297 TI - Respiratory syncytial virus infection among intubated adults in a university medical intensive care unit. AB - Respiratory syncytial virus is the major cause of lower respiratory tract infection in children. Adults who are immunocompromised, aged, institutionalized, and/or have underlying medical diseases may be at risk for severe RSV infection. Intubated adults in an MICU were evaluated for evidence of RSV infection. Respiratory secretions were analyzed by cell culture and RSV EIA. Serologic testing was obtained. Respiratory secretions from MICU personnel with acute respiratory symptoms and patients admitted for pneumonia, asthma, or COPD also were screened. Five of 11 intubated patients had evidence of RSV infection. One of seven MICU employees and four of 48 ward patients had RSV-positive respiratory secretions. During community outbreaks of RSV infection, adults admitted to an MICU already may be infected with RSV; those admitted for other reasons are at risk for nosocomial infection. Patients occupying other hospital units and personnel may be instrumental in the nosocomial dissemination of RSV. PMID- 1935298 TI - Urinary desmosine excretion as a marker of lung injury in the adult respiratory distress syndrome. AB - Desmosine, the intermolecular and intramolecular cross link between the chains of elastin polypeptide, may be useful as a marker of a lung injury in adult respiratory distress syndrome (ARDS). A radioimmunoassay for rabbit antibody developed against desmosine, conjugated to bovine serum albumin, can detect as little as 100 pg of desmosine in plasma or urine. Desmosine is not metabolically absorbed, reused, or catabolized by the body, but rather eliminated unchanged in the urine as low molecular weight peptides. The lung is relatively rich in elastin, and we reasoned that a timed collection could be used as an index of elastin degradation in vivo. A 2-h collection of urine for desmosine assay was obtained at the time of Swan-Ganz catheter insertion in 41 consecutive patients. On the basis of clinical and initial Swan-Ganz catheter data, the patients were assigned to one of three groups: an ARDS group (n = 12); a cardiogenic pulmonary edema (CPE) group (n = 12); and a critically ill, nonpulmonary edema group (NPE, n = 17). The mean urine desmosine concentration (mg/L) for the ARDS group (0.728 +/- 0.22 SE) differed from the CPE group (0.149 +/- 0.07; p less than 0.001). The total excretion (microgram/2 h) was 64.95 +/- 24.7 in the ARDS group and 24.71 +/ 11.7 in the CPE group (p less than 0.05). Urine desmosine concentration/serum creatinine index for the ARDS group (0.78 +/- 0.28) was greater than in the CPE group (0.07 +/- 0.04; p = 0.019). Desmosine excretion was increased in the NPE group compared with CPE and ARDS groups, possibly reflecting heterogeneity in this group. In the differentiation of ARDS from CPE, we conclude that substantial increases in urinary desmosine excretion favor a diagnosis of ARDS. PMID- 1935299 TI - Fever, hyperdynamic shock, and multiple-system organ failure. A pseudo-sepsis syndrome associated with chronic salicylate intoxication. AB - OBJECTIVE: To describe a sepsis-like syndrome associated with chronic salicylate intoxication. DESIGN: Retrospective clinical study. SETTING: University affiliated county hospital. PATIENTS: Five patients who became accidentally intoxicated while ingesting salicylates on a long-term daily basis. RESULTS OF DATA ANALYSIS: All five salicylate-intoxicated patients had clinical and laboratory features that were highly suggestive of sepsis, but no bacteriologic or pathologic evidence of infection could be documented. Features included fever, leukocytosis with increased band forms, hypotension with a reduced SVR and multiple system organ failure (ARDS, encephalopathy, renal failure, and DIC). A diagnosis of salicylate intoxication was made at the time of admission to the hospital in only one case. In the other four cases, the presumptive diagnosis was sepsis; a correct diagnosis of salicylate intoxication was not established until between 16 h and 10 days after admission in these four cases. Two patients died, one patient required permanent hemodialysis, and two patients recovered fully only after prolonged and complicated hospitalizations. The pathogenesis of this syndrome is uncertain. In two cases, serum levels of TNF-alpha, IL-1 beta and IL 6 were measured by ELISA. In both cases serum IL-6 was markedly increased, and in one case serum TNF-alpha was also elevated. CONCLUSION: Occult salicylate intoxication should be considered when apparent sepsis syndrome occurs without a readily easily identifiable source of infection. PMID- 1935300 TI - Deficiency of alveolar fluid glutathione in patients with sepsis and the adult respiratory distress syndrome. AB - The adult respiratory distress syndrome (ARDS) is a devastating clinical illness characterized by refractory hypoxemia and high-permeability pulmonary edema. Reactive oxygen species such as hydrogen peroxide and hypochlorous acid may play a key role in the pathogenesis of the acute lung injury. Glutathione (GSH) is a tripeptide that is able to react with and effectively neutralize oxidants such as hydrogen peroxide and hypochlorous acid. The present study found that the alveolar epithelial lining fluid of patients with ARDS was deficient in total GSH compared to normal subjects (21.7 mumols +/- 7.8 mumols vs 91.8 mumols +/- 14.5 mumols; p = 0.002). In addition, if GSH was measured in unconcentrated bronchoalveolar lavage (BAL) fluid and indexed to total BAL protein, there was also a deficiency in patients with ARDS compared to normal subjects (0.004 +/- 0.003 nmol of GSH per microgram of total protein vs 0.026 +/- 0.005 nmol of GSH per microgram of total protein; p = 0.002). Since patients with ARDS are subjected to an increased burden of oxidants in the alveolar fluid, principally released by recruited neutrophils, this deficiency of GSH may predispose these patients to enhanced lung cell injury. PMID- 1935301 TI - Defining patient competence for medical decision making. PMID- 1935302 TI - Rapid and accurate diagnosis of pulmonary emboli in a canine model using intravascular ultrasound imaging. AB - We utilized intravascular ultrasound (IVUS) imaging in a canine pulmonary embolism model to visualize experimental emboli. The images obtained were compared with those obtained by single-plane pulmonary arteriography in each of six animals. The vessel lumen appeared patent by both methods prior to injection of autologous clot. After thrombi were injected, the vessels were again imaged using both techniques. Intravascular ultrasound was 100 percent sensitive in detecting emboli, and visualization was always rapid. There were no complications. It appears that IVUS imaging is a sensitive method for documenting the presence of clot in a canine pulmonary embolism model. PMID- 1935304 TI - Positive pressure ventilation. Alternate modes. PMID- 1935303 TI - Acute hypokalemia and inducibility of ventricular tachyarrhythmia in a nonischemic canine model. AB - Inducibility of sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) by programmed ventricular stimulation following acute hypokalemia was studied in 21 anesthetized dogs free of inducible ventricular tachyarrhythmias at baseline. The control mean serum potassium concentration of 3.65 mEq/L was decreased to 2.14 mEq/L by insulin and furosemide administration. Inducibility of arrhythmias was also assessed following isoproterenol infusion before and after induction of hypokalemia. None of the animals developed sustained VT. Only one animal developed VF following hypokalemia (p greater than 0.05). Two normokalemic animals and five hypokalemic animals developed VF following isoproterenol infusion; this difference was not significant (p greater than 0.05). In this study, hypokalemia did not predispose to the development of a substrate necessary for the genesis and maintenance of VT. The inducibility of VF following hypokalemia was not significantly enhanced and appears to be related to the "aggressive" stimulation protocol. PMID- 1935305 TI - Respiratory muscle fatigue and breathing pattern. AB - The major determinants of VO2 resp and, thus, diaphragmatic endurance are the tension-time index, work rate and lung volume. Changes in breathing pattern that adversely affect any of these factors can impair diaphragmatic endurance. A TTdi above 0.15-0.18 indicates a potentially fatiguing pattern of contraction. However, fatigue may occur at a TTdi below 0.15 if the work rate is sufficiently high or the Pdimax is not measured at the prevailing lung volume. Inspiratory muscle fatigue usually elicits an increase in minute ventilation and respiratory rate and to a lesser degree a reduction in tidal volume. However, fatigue may not always be accompanied by changes in breathing pattern. Furthermore, fatigue may sometimes result in a reduction rather than an increase in motor outflow to the respiratory muscles. Finally, abdominal paradox initially considered to be characteristic clinical sign of inspiratory muscle fatigue appears to be due to increases in respiratory load rather than to muscle fatigue. PMID- 1935307 TI - Esophageal reflux and variant angina pectoris. PMID- 1935306 TI - The role of bronchoscopy in pulmonary complications due to mustard gas inhalation. AB - Over the last five years we have repetitively treated a group of 21 Iranian soldiers who developed pulmonary complications as a result of severe inhalation injury due to mustard gas during the Iran-Iraq war. Early respiratory manifestations included hemorrhagic inflammation of the tracheobronchial tree accompanied by severe erosions. Secondary complications consisted of chronic infections, suppurative bronchitis, and extensive stenotic process of the entire tracheobronchial tree with life-threatening sequelae. After a delay of up to 15 months, scars, ulcers, and strictures developed in the central airways. Progressive deterioration of gas exchange was common. At this point, bronchoscopy, both diagnostic and therapeutic, was invaluable in evaluating the conditions in these patients since many required multiple therapeutic bronchoscopies. Repeated bougienage of the stenotic tracheobronchial lesions and laser photoresection of scarring tissue was life-saving. The recurrence rate of stenosis was very high, with intervals of less than six months on the average. One pneumonectomy was necessary, with the excised lung showing bronchiectasis and chronic pneumonia. To this date we have performed 146 therapeutic bronchoscopies. In four patients, silicone stents had to be implanted. One patient received brachytherapy and external beam radiation therapy in an effort to prevent continued scarring and life-threatening stenoses of the tracheobronchial tree. Our experience demonstrates the extreme usefulness of bronchoscopy in the diagnosis and treatment of pulmonary complications due to inhalation of poisonous gases. PMID- 1935308 TI - Hard nontender masses over the left mandible and scapula. PMID- 1935309 TI - Chest pain in a debilitated postoperative patient. PMID- 1935310 TI - Miliary pulmonary infection caused by Mycobacterium terrae in an autologous bone marrow transplant patient. AB - A 64-year-old woman with ovarian carcinoma that had been treated with high-dose chemotherapy and autologous bone marrow transplantation presented with a maculopapular rash on the extremities and miliary infiltrates evident on chest roentgenogram. Transbronchial biopsy specimens revealed caseating granulomas, and cultures grew Mycobacterium terrae. Six weeks after therapy with isoniazid, rifampin, and pyrazinamide was begun, her rash and pulmonary infiltrates had cleared, despite the in vitro resistance to these drugs and continued spread of her carcinoma. This case suggests that spontaneous resolution may be part of the natural history of M terrae infections. PMID- 1935311 TI - Hypercalcemia induced by parathyroid hormone-related protein from lung cancer tissue. AB - Most lung carcinomas with hypercalcemia are usually unresectable. However, this case was resectable and the serum calcium level was normalized after the operation. Messenger RNA of the precursor of PTH-related protein (PTHrP), a substance that may be one of the causes of hypercalcemia in malignant neoplasms, was identified in the tumor tissue of the patient. The patient was a 60-year-old man with squamous cell carcinoma originating from the posterior basal segment of the left lung and invading the main bronchus and left atrium. The serum calcium level was 14.3 mg/dl, preoperatively. Pneumonectomy with partial left atrium resection was carried out and the serum calcium level became normal postoperatively. Three months following the operation, this measurement was 9.4 mg/dl, but increased to 16.2 mg/dl at four months, at which time he experienced lumbago and chest pain. The patient died eight months following the operation from uncontrollable renal failure. In the tumor tissue, mRNA of PTHrP precursor was identified. To our knowledge, this is the first case of lung cancer that could be resected, and in which PTHrP was found present. PMID- 1935312 TI - Extrapulmonary thoracic restriction (hidebound chest) complicating eosinophilic fasciitis. AB - Eosinophilic fasciitis (EF) is an unusual disorder characterized by diffuse skin thickening and induration due to inflammation within the deep fascia; visceral involvement is generally mild or absent. A patient with biopsy-proved EF developed progressive respiratory limitation. Physical examination revealed marked induration of the thoracic integument with a severely limited chest wall excursion. Total lung capacity was 62 percent of predicted with a normal corrected Dco and maximal inspiratory force; a chest computed tomogram with thin sections showed no evidence of parenchymal lung disease. Extrapulmonary thoracic restriction ("hidebound chest") has not been previously reported to complicate EF. PMID- 1935313 TI - Death due to diffuse alveolar hemorrhage in a child with pulmonary veno-occlusive disease. AB - Pulmonary veno-occlusive disease (PVOD) occurred in a six-year-old girl. Investigation of a number of proposed causes for this uncommon condition and histologic progression of disease are documented. To our knowledge, this is the first case of PVOD in which death was due to massive alveolar hemorrhage. PMID- 1935314 TI - Endobronchial and parenchymal juvenile laryngotracheobronchial papillomatosis. Effect of photodynamic therapy. AB - Juvenile laryngotracheobronchial papillomatosis (JLTBP) is a recurrent, prolonged disease usually confined to the upper airway. Rarely, tracheobronchial tree or lung parenchymal involvement occurs. The various therapeutic interventions are often unsuccessful once extralaryngeal involvement becomes apparent. Photodynamic therapy (PDT) has been successful in eradicating JLTBP in a few case reports. We present a case of extensive JLTBP with parenchymal involvement treated with multiple courses of PDT. We demonstrated temporary regression of endobronchial papillomas, but no change in parenchymal lesions. Recurrent endobronchial disease was most likely related to reinfection from parenchymal lesions inaccessible to PDT. PMID- 1935315 TI - Successful treatment of central sleep apnea with an oral prosthesis. AB - Two cases of polygraphically defined central sleep apnea were successfully treated with the tongue retaining device, an oral prosthesis designed to reduce hypopharyngeal obstruction. The tongue retaining device may be an alternative to CPAP in the treatment of some cases of central sleep apnea. PMID- 1935316 TI - Apical Pneumocystis carinii pneumonia in AIDS patients not receiving inhaled pentamidine prophylaxis. AB - Isolated apical Pneumocystis carinii pneumonia might develop in AIDS patients receiving aerosolized pentamidine prophylaxis. Demonstrated here are two cases of apical P carinii pneumonia occurring in patients not receiving inhaled pentamidine prophylaxis. Such isolated apical localization of P carinii should be differentiated from tuberculosis and fungal infection. PMID- 1935317 TI - Functional laryngeal obstruction relieved by panting. AB - A 49-year-old man presented with a two-day history of severe recurrent dyspnea and inspiratory stridor. A chest roentgenogram, computed tomographic scan of the neck, direct laryngoscopy, and bronchoscopy excluded organic upper airway obstruction. Laryngospasm occurred during the bronchoscopy. Although flow volume loops revealed severe upper airway obstruction (inspiratory and expiratory), airway resistance measured plethysmographically (during panting) was normal. Because of this observation, panting was recommended for relief of the patient's recurrent attacks of functional laryngeal obstruction. The panting maneuver immediately and completely relieved all 25 to 30 subsequent attacks. After the patient recovered clinically, a flow volume loop was repeated and was found to be normal. The marked discrepancy between severe flow limitation (as detected by flow volume loops) and normal airway resistance (measured plethysmographically) may be a diagnostic test for functional laryngeal obstruction, and panting may be an effective emergency measure for its relief. Relief by panting may also suggest the diagnosis. A second patient with an almost identical symptom complex is described, in whom the panting maneuver was also dramatically successful in promptly aborting recurrent severe attacks of airway obstruction and stridor. PMID- 1935318 TI - Resolution of ventricular tachycardia and endocardial tuberculoma following antituberculosis therapy. AB - A 23-year-old woman presented with sustained ventricular tachycardia and was found to have an endocardial mass by echocardiography and by magnetic resonance imaging. The diagnosis of cardiac endocardial tuberculoma was made, and she was treated with antituberculous therapy and an antiarrhythmic drug for one year. After a year, the mass was no longer present, and with all antiarrhythmic medications stopped, ventricular tachycardia could no longer be induced by electrophysiologic study. There has been no clinical recurrence. PMID- 1935319 TI - Omental herniation through the foramen of Morgagni. Diagnosis with chest computed tomography. AB - The fat accumulation most frequently seen in the peridiaphragmatic areas represents herniations of abdominal fat or epicardial fat pad. We present a patient with a large fatty mass after 10 months of corticosteroid therapy in which computed tomography demonstrated omental vessels, thus proving that it was omental herniation through Morgagni's foramen. PMID- 1935320 TI - Continuous six-month infusion of intravenous nitroglycerin in a patient awaiting cardiac transplantation. AB - We report a patient with ischemic cardiomyopathy who was treated with a continuous high dose infusion of intravenous nitroglycerin for six months while awaiting cardiac transplantation. Surprisingly, methemoglobinemia did not develop and nitroglycerin continued to be clinically effective in relieving angina during the six-month period. We believe this to be the first reported instance of the safe use of such prolonged infusion of intravenous nitroglycerin. PMID- 1935322 TI - False aneurysm of the left ventricle due to a penetrating chest wound. AB - A 24-year-old white man had a knife chest wound, and four months after this event, manifested progressive dyspnea. A false aneurysm of the left ventricle was diagnosed by 2D echocardiogram. Surgical resection of the aneurysmal sac with closure of the orifice of the lateral wall of the left ventricle was performed successfully. PMID- 1935321 TI - Churg-Strauss angiitis. Arguments favoring the responsibility of inhaled antigens. AB - A 27-year-old man presented with relapsing vascular limb purpura, pulmonary infiltrates and cranial nerve palsies occurring after exposure to pigeons. A lung biopsy specimen showed Churg-Strauss angiitis. Actinomycetes were observed in pneumocytes. The circumstances preceding clinical manifestations and pathologic findings favored the diagnosis of pulmonary vasculitis as a consequence of inhaled antigen. Recovery was obtained after treatment with prednisone, cyclophosphamide, and plasma exchanges. PMID- 1935324 TI - Rapid percutaneous tracheostomy. PMID- 1935323 TI - Cytostatic activity of pulmonary alveolar macrophages in lung cancer patients. PMID- 1935325 TI - Use of pulmonary artery catheterization in patients with acute myocardial infarction. PMID- 1935326 TI - Use of pulse oximeter in new SaO2-oriented technique for bronchopulmonary lavage. PMID- 1935327 TI - Elevated pulmonary artery pressure as a predictor of mortality. PMID- 1935328 TI - Subclinical pulmonary involvement in essential mixed cryoglobulinemia assessed by bronchoalveolar lavage. PMID- 1935329 TI - Pleural fluid adenosine deaminase and lysozyme levels in the diagnosis of tuberculosis. PMID- 1935330 TI - Peak expiratory flow rates in possible occupational asthma. PMID- 1935331 TI - HIV infection and homeless adolescents. AB - Homeless adolescents are at extremely high risk for acquiring HIV infection, as the literature reviewed in this paper documents. Sexual and drug use behaviors that put these adolescents at risk are described, and new models of service for these youths are outlined. PMID- 1935332 TI - The spiritual healing "defense" in criminal prosecutions for crimes against children. AB - Spiritual healing as a defense in cases of parents' rejection of medical treatment for their sick children involves questions of the rights of parents, of children, of the state, and of the U.S. Constitution. State legislation protecting rights of religion, long on the books, is coming into conflict with new legislation on child abuse. This article reviews the current picture of applicable laws in the states and in recent court cases. Limiting the use of spiritual healing as a legal defense is an emerging trend. PMID- 1935333 TI - Self psychology in child welfare practice. AB - The use of self psychology, a theory first developed by Kohut, in formulating and guiding treatment planning and implementation in child welfare, is discussed, with accompanying illustrations from child welfare practice of key concepts. PMID- 1935334 TI - Ethnic-sensitive work with Hmong refugee children. AB - This article examines three distinguishing characteristics of Hmong culture, and gives examples of the problems these differences can create in serving Hmong children and their families. PMID- 1935335 TI - PARTNERS: a model program for special-needs adoptive families in stress. AB - That adoption status, once begun, does not end for any adoptive family, and that agencies must be ready to help adoptive families whenever needed, has been generally agreed. For families that adopt special-needs children, the availability of help at all times is imperative and involves special considerations. This article sets forth the kinds of services that are needed, and describes a program particularly designed for this purpose. PMID- 1935336 TI - Childhood experience, interpersonal development, and reproductive strategy: and evolutionary theory of socialization. AB - The concept of "reproductive strategy" drawn from the field of behavioral ecology is applied to the study of childhood experience and interpersonal development in order to develop an evolutionary theory of socialization. The theory is presented in terms of 2 divergent development pathways considered to promote reproductive success in the contexts in which they have arisen. One is characterized, in childhood, by a stressful rearing environment and the development of insecure attachments to parents and subsequent behavior problems; in adolescence by early pubertal development and precocious sexuality; and, in adulthood, by unstable pair bonds and limited investment in child rearing, whereas the other is characterized by the opposite. The relation between this theory and prevailing theories of socialization, specifically, attachment, social-learning, and discrete-emotions theory, is considered and research consistent with our evolutionary theory is reviewed. Finally, directions for future research are discussed. PMID- 1935337 TI - When is an evolutionary approach useful? AB - Evidence that human behavior is or has been adaptive comes from the likelihood that it would have been useful in our environment of evolutionary adaptedness, that it forms a coherent whole with other characteristics, and that variants contribute or would be likely to contribute to reproductive success. Belsky et al. use the second and third of these, though on the third their evidence is somewhat tenuous. However, their thesis does integrate diverse facts about parenting and development. In general an evolutionary approach is useful if it integrates diverse facts, if it aids clinical practice, and if it helps us toward a full understanding of human nature. PMID- 1935338 TI - Different reproductive strategies in males and females. AB - The claim for a connection between stressful, unstable childhood environments and early pubertal maturation has only modest empirical support. However, granting the claim for purposes of discussion, and taking an evolutionary perspective, it is argued here that early puberty need not imply a shift from a "quality" toward a "quantity" reproductive strategy. Indeed, for females to make such a shift when they cannot count on secure pair bonding or paternal investment from a male would not serve their inclusive fitness interests; indeed, probably the reverse. Delayed puberty among juveniles with secure, long-continued bonds with the parental generation may serve a different evolutionary function: to minimize inbreeding. Nonevolutionary factors are more than adequate to account for precocious sexuality in individuals with stressful childhood histories. PMID- 1935339 TI - Attachment in monkey infants raised in variable- and low-demand environments. AB - 12 bonnet macaque (Macaca radiata) mother-infant dyads were studied. For 14 weeks, beginning when the infants were a mean age of 11.2 weeks, the dyads were housed and observed under different foraging-demand conditions for the mothers: 6 dyads in a low-foraging-demand (LFD) condition and 6 dyads in a variable-foraging demand (VFD) conditions. For VFD mothers, demand varied between low and high in 2 week blocks. Differences between the LFD and VFD groups were minimal during this period; there was, however, more maternal grooming and shorter separation bouts in the VFD group than in the LFD group. The dyads were then challenged by brief introductions to a novel environment. The challenge revealed that frequency of breaking dyadic contact and levels of play were significantly lower for the VFD infants than for the LFD infants, perhaps as a consequence of less secure attachment. PMID- 1935340 TI - Neurobehavioral syndromes in cocaine-exposed newborn infants. AB - The effects of fetal cocaine exposure on newborn cry characteristics were studied in 80 cocaine-exposed and 80 control infants. The groups were stratified to be similar on maternal demographic characteristics and maternal use of other illegal substances and alcohol during pregnancy. The hypothesis was that excitable cry characteristics were related to the direct effects of cocaine, while depressed cry characteristics were related to the indirect effects of cocaine secondary to low birthweight. Structural equation modeling (EQS) showed direct effects of cocaine on cries with a longer duration, higher fundamental frequency, and a higher and more variable first formant frequency. Indirect effects of cocaine secondary to low birthweight resulted in cries with a longer latency, fewer utterances, lower amplitude, and more dysphonation. Cocaine-exposed infants had a lower birthweight, shorter length, and smaller head circumference than the unexposed controls. Findings were consistent with the notion that 2 neurobehavioral syndromes, excitable and depressed, can be described in cocaine exposed infants, and that these 2 syndromes are due, respectively, to direct neurotoxic effects and indirect effects secondary to intrauterine growth retardation. PMID- 1935341 TI - Asymmetries in infant cross-modal transfer. AB - 3 groups of 12-month-olds were tested for cross-modal and intramodal transfer of information about shape. Infants were given either visual (V) or tactual (T) familiarization and then tested for visual recognition (V-V, T-V) or tactual recognition (T-T, V-T). Transfer was tested after either 15, 30, or 60 sec familiarization. Overall, intramodal transfer was superior to cross-modal transfer. Whereas the V-V condition was easiest of all, the T-T condition proved easier than V-T cross-modal transfer, although it was no more difficult than T-V transfer; cross-modal asymmetries appeared, with T-V easier than V-T. The asymmetry in cross-modal transfer could not be explained by intramodal factors. Possible bases for cross-modal asymmetries were discussed. PMID- 1935342 TI - Early differentiation of causal mechanisms appropriate to biological and nonbiological kinds. AB - Although Piaget characterized young children as precausal until about 7-8 years of age, recent work indicates that preschoolers do honor fundamental principles of causality. This literature has mainly focused on general principles invoked in reasoning about mechanical events. By contrast, the present study examined whether children differentiate between the causal mechanisms appropriate for different conceptual domains. The results of 3 preliminary investigations and 1 main experiment suggested that preschoolers prefer natural mechanisms for color inheritance in biological kinds, particularly when causal substrates resemble their consequences. By contrast, the same children recognized the importance of human intentions in producing the color of an artifact, and also judged that mechanical mechanisms serve to mediate between intentions and outcomes. The results are relevant to recent studies on the development of biological thought, and overall suggest that early causal reasoning reflects both domain-specific and domain-general principles. PMID- 1935343 TI - Mother-child conversation in different social classes and communicative settings. AB - 30 working-class and 33 upper-middle-class mothers were videotaped in dyadic interaction with their 18-29-month-old children in 4 settings--mealtime, dressing, book reading, and toy play. Samples of the mothers' adult-directed speech also were collected. There were significant social class differences in the mothers' child-directed speech and some parallel social class differences in the mothers' adult-directed speech. These findings suggested that some social class differences in child-directed speech may be instances of more general class differences in language use. There also were main effects of communicative setting on mothers' child-directed speech and interaction effects in which setting moderated the size of the class differences in maternal speech. These findings suggested that the amount of time mothers spend interacting with their children in different contexts may be at least as important an influence on children's linguistic experience as are average characteristics of their mothers' speech. PMID- 1935344 TI - Influence and involvement in children's discourse: age, gender, and partner effects. AB - Children's discourse with peers was examined in relation to speaker gender, partner gender, and age level. 138 children were matched with either a same- or an other-gender peer at the early childhood and middle childhood age levels (median ages = 5 and 7 years) and asked to play with puppets for 10 min. Speech acts were coded as either collaborative (affiliative involvement and direct influence), controlling (distancing involvement and direct influence), obliging (affiliative involvement and nondirect influence), or withdrawing (distancing involvement and nondirect influence). Girls' and boys' communication patterns were more similar than different. However, gender-related differences with medium to large effect sizes were found. Gender-typed communications were more likely at the middle childhood than the early childhood age level and in same-gender than mixed-gender dyads. The findings are interpreted in terms of developmental and contextual accounts of gender and social behavior. Recommendations for future research are offered. PMID- 1935345 TI - The role of aggression in peer relations: an analysis of aggression episodes in boys' play groups. AB - Although aggression is frequently cited as a major cause of peer social rejection, no more than half of all aggressive children are rejected. Aggressive episode data from experimental play groups of 7- and 9-year-old black males were coded to examine whether qualitative aspects of aggressive behavior, as well as frequency of aggression, determine the relation between aggressiveness and peer rejection. Reactive aggression and bullying were related to peer status among 9 year-olds, but not 7-year-olds, whereas instrumental aggression was characteristic of highly aggressive, rejected boys at both ages. Qualitative features of aggressive interaction suggested a greater level of hostility toward peers and a tendency to violate norms for aggressive exchange among rejected, aggressive boys at both ages in contrast to other groups of boys. The descriptive data provide a distinctive picture of reactive, instrumental, and bullying aggression as well as differing social norms for target and aggressor behavior in each of these 3 types of aggression. PMID- 1935346 TI - Understanding differences in moral judgments: the role of informational assumptions. AB - This study examined differences in moral judgments as they relate to informational assumptions. It was hypothesized that (1) differences in moral judgments are related to differences in informational assumptions, (2) moral judgments change if the information believed to be true changes, and (3) the relation between informational assumptions and moral judgments is not affected by age. 72 subjects (aged 11-9, 15-10, and 21-3) evaluated events concerning welfare, justice, and rights and reevaluated them in light of the opposite information. A significant relation was found between the evaluations and the informational assumptions, and 80% of the evaluations changed in response to informational changes. The relation between evaluations and informational assumptions was significant within each age group. These findings demonstrated that informational assumptions are a source of variation in moral judgments and underscored the need to distinguish between the 2 types of judgments when studying differences in moral reasoning. PMID- 1935348 TI - Advances in interventional radiology. PMID- 1935347 TI - Quality infant day-care and grade school behavior and performance. AB - Relations between attendance in stable high-quality day-care programs and grade school behavior and performance were determined using 2 longitudinal data sets. The first sample included grade school children who had received stable, full time infant day-care and preschool day-care until they reached school age in the same high-quality day-care center. In this sample the amount of time (months) spent in full-time center care was positively related to the number of friends and extracurricular activities of the children. In addition, more time in the center was positively related to parents' ratings of the children's emotional well-being, leadership, popularity, attractiveness, and assertiveness and negatively related to aggressivity. Study 2 sampled sixth graders who had also received varying amounts (months) of stable full-time day-care, but this group attended a variety of quality day-care centers. In this sample the amount of time in day-care was related to the teachers' ratings of their emotional well-being, attractiveness, and assertiveness. In addition, children with more time in high quality day-care showed more physical affection during peer interactions, were more often assigned to the gifted program, and received higher math grades. PMID- 1935350 TI - Renal metastases of choriocarcinoma. A clinicopathological study of 31 cases. AB - From 1949 through 1978, 31 patients with renal metastasis were diagnosed in a total of 448 cases of choriocarcinoma admitted to our hospital, giving an incidence of 6.9%. Renal metastasis was invariably preceded by pulmonary metastases and usually accompanied by other visceral metastases, indicating that renal metastasis is the result of dissemination of tumor cells secondarily from lung metastasis through the general circulation and should be categorized as arterial metastasis. Pyelogram is useful in the presence of medullary invasion by the tumor. Renal metastatic tumors are very sensitive to chemotherapy. Good response to chemical agents may be due to high drug concentration attained in the kidney tissue during excretion. Since successful treatment of renal metastasis by chemotherapy alone may be obtained, patients can be spared a major operation without jeopardizing the prognosis. PMID- 1935349 TI - Anti-FD4 idiotypic antibody mimicking human gastric cancer-associated antigen. AB - Rabbits were immunized with the Fab fragment of a murine monoclonal antibody (McAb) PD4 against human gastric cancer to produce anti-PD4-idiotypic antibody (alpha PD4-Ab2). The alpha PD4-Ab2 could not only competitively inhibit binding of McAb PD4 to gastric cancer cell MGC803, but also induce delayed-type hypersensitivity (DTH) to MGC803 in mice. Spleen cells of mice immunized with alpha PD4-Ab2 were fused with myeloma cell SP2/0 to form hybridoma secreting Ab3 which could be bound to target cell MGC803. McAb C7-Ab3, one of the Ab3, could selectively react with a 40 kD tumor-associated antigen located on MGC803 cell membrane, as well as McAb PD4. The results indicate that alpha PD4-Ab2 possesses determinants (internal image antigen) similar to those on MGC803, and could mimic human gastric cancer-associated antigen. PMID- 1935351 TI - Laser ablation ability of different fiber tips on human arteries. The role of photothermal effect. AB - To compare laser ablation abilities of bare tip and metal probe as well as spectraprobe, specimens from human normal and atherosclerotic aorta were irradiated with Nd-YAG laser. To evaluate the influence of photothermal effect thermal energy productions of 3 tips were measured with a calorimeter. The results showed that the bare tip produced the most effective ablation in arterial atheroma, followed by the metal probe and the spectraprobe. Similarly, the ratio of the ablation area on atheroma to that on normal vessel was the best with the bare tip and the worst with the spectraprobe. However, the extent of surrounding tissue damage adjacent to the ablation crater was the largest with the bare tip and the smallest with the spectraprobe. These differences cannot be explained only by variations in the photothermal effect, since thermal energy production is proved to be almost equal among the 3 laser fiber tips. PMID- 1935352 TI - Piezo-electric lithotripter in the treatment of pediatric renal calculi. AB - EDAP LT-01 lithotripter was used to treat 23 stone events in 17 pediatric patients. The mean age of the patients at treatment was 7.2 years, the youngest being 18 months. The mean stone size was 1.22 cm. Thirty-six sessions of extra corporeal shock wave lithotripsy (ESWL) treatment were necessary for the 23 stones. The focal point pressure power was 60-100% (540-900 Bar), the treating period 0.5-1 hour and the frequency 1.25-2.5 Hz. The patients were stone free in 2 months. IVU or ultrasonography showed that there was no renal dysfunction and retardation of renal growth after ESWL. Appropriate ESWL monotherapy in pediatric patients may produce results comparable to those in adults. Factors known to affect treatment results in adults also influence the results in children and should be considered in terms of the applicability of ESWL to any particular pediatric patient. PMID- 1935353 TI - Comparative efficacy of levo-praziquantel and praziquantel in treatment of schistosomiasis japonica at a single dose. AB - The result of a randomized double blind comparison of therapeutic efficacy of single doses of levo-praziquantel (L-PZQ) and praziquantel (PZQ) in the treatment of 139 matched pairs of proved cases of schistosomiasis japonica was reported, 268 were chronic early cases and 10 were late cases. The dosage of L-PQZ was 20 mg/kg, and that of PZQ was 40 mg/kg. Four and 6 months after treatment the stool ova negative conversion rates were 94.8% and 96.3% for the L-PZQ group, and 97.1% and 94.0% for the PZQ group respectively (P greater than 0.05). PMID- 1935354 TI - Observations on experimental infection of periodic Brugia malayi in man. AB - Three volunteers were inoculated with different numbers of infective larvae of periodic Brugia malayi from an artificially infected Meriones unguiculatus. At different times after inoculation, the volunteers developed clinical manifestations such as chills, fever, cough, asthma, skin itching, edema, adenolymphangitis and eosinophilia. Microfilaremia was first detected at 41 and 46 weeks after inoculation in two subjects. At 11 weeks, the percentage of E rosette forming lymphocytes in these subjects was below the normal level. Specific antibody was first detected in three volunteers at 2, 3 and 5 weeks after inoculation, respectively, and increased to various extent at 12-16 weeks, but decreased in varying degrees at 44-56 weeks. The results also showed that antibody titres fluctuated at different periods of infection. PMID- 1935355 TI - Twenty-item behavioral neurological assessment for normal newborns in 12 cities of China. AB - Based on the method of Brazelton and Amiel-Tison for behavioral neurological measurement in the newborn and our own experience, we formulated a 20-item neonatal behavioral neurological assessment (NBNA). For setting up a practical method and a normal range of its scores in China, we examined 714 normal newborns (male 369, female 345), with NBNA at the age of 2-3, 12-14, 26-28 days for a total of 2,142 times, in 12 provinces of China from May to October 1988. NBNA contains 5 clusters: behavior (6 items); passive tone (4 items); active tone (4 items); primary reflexes (3 items); and general assessment (3 items). Each item has 3 scales (0,1,2). Twenty items have a maximum of 40 scores. Among the 2,142 times examined, 90.4% of the 714 newborns had 39-40 scores, 97% greater than 37 and none below 35. Measurements of the first, second and third time revealed that the total scores increased with age. The difference was statistically significant. The abilities of auditory and visual orientations and active neck tone improved obviously with age. NBNA shows distinct stability and reliability. The score is not influenced by geographic location; the scoring system is simple and the manipulation takes only ten minutes. PMID- 1935356 TI - Modified Wicomb's apparatus for preservation of heart for 24 hours. AB - To prolong the time of heart preservation, we modified the Wicomb's perfusion apparatus, in which oxygen flow acts as the source of power and provides oxygenation for the perfused myocardium. Ten adult porcine hearts which had been preserved for 24 hours were resuscitated successfully and continued to beat steadily for more than 1.5-3 hours after reperfusion. Myocardial ultrastructure was observed at the end of preservation and 15-120 minutes after reperfusion. The damages of the myocardial ultrastructure at the end of preservation were reversible. PMID- 1935357 TI - Transfer of upper pectoralis major flap for functional reconstruction of deltoid muscle. AB - Since January 1984, functional reconstruction of the deltoid muscle using transfer of the upper part of the pectoralis major muscle has been performed in 7 patients with deltoid dysfunction. 5-20 months follow-up (average 11) revealed marked improvement in 6 patients. During the operation, the superior and inferior parts of the pectoralis major muscle were bluntly dissected and sectioned. The upper part of this muscle was turned over and transferred to the site normally occupied by the deltoid muscle. The transposed muscle contributed to both abduction and flexion of the shoulder. The efficacy of abduction was reinforced by the increased arm of action. PMID- 1935358 TI - Hemiparkinsonism in monkeys following unilateral common carotid artery infusion of MPTP. A study of behavior, biochemistry and histology. AB - After local surgical exposure, we administrated 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) directly into the right common carotid artery of 5 rhesus monkeys. All the monkeys manifested akinesia, rigidity and postural tremor of the contralateral limbs, and spontaneous circling toward the MPTP treated side. These disturbances began to appear 3-4 days after injection, peaking at one month, and continued until the day of sacrifice. After treatment with madopar and apomorphine, marked improvements of the motor impairments appeared and a striking reversal of the direction of rotation away from the MPTP-treated side occurred in a dose-dependent manner. The ipsilateral neurotoxicity was confirmed biochemically by 99% reduction in the caudate-putamen dopamine levels and histologically by selective cell loss in the substantia nigra of the MPTP-treated side. It is concluded that this primate model of hemiparkinsonism is easy to reproduce and life is maintained with good health otherwise. So it may be more feasible for behavioral and pharmacological studies of Parkinson's disease. PMID- 1935359 TI - Changes of immunoreactive TRH in cerebrospinal fluid and plasma after acute head injury and its clinical significance. AB - Using radioimmunoassay (RIA) concentrations of immunoreactive TRH (TRH-ir) in cerebrospinal fluid (CSF) and plasma were determined after acute head injury in 29 patients. The results showed that the concentrations of TRH-ir (pmol/L) in CSF and plasma on the days when injuries were sustained were 29.25 +/- 8.92 pg/ml and 30.29 +/- 8.26 (1 pg/ml = 2.8 pmol/L) in mildly (n = 12), 57.78 +/- 11.72 and 65.27 +/- 8.57 in moderately (n = 9), and 70.09 +/- 7.58 and 85.65 +/- 7.92 in severely (n = 8), head-injured patients. While the concentrations of TRH-ir in CSF and plasma were 25.11 +/- 11.85 and 27.90 +/- 11.39 in the control group (n = 10). Dynamic observations revealed that the contents of TRH-ir in CSF and plasma were gradually recovered to their control levels when improvement of the head injured patients took place. But they were significantly decreased and became much lower than the control levels in patients with poor prognosis. These results suggest that the assay of TRH-ir in CSF and plasma has clinical significance in reflecting the severity and prognosis of acute head-injured patients. PMID- 1935361 TI - Advances in the pharmacological studies of radix Angelica sinensis (Oliv) Diels (Chinese Danggui). PMID- 1935360 TI - Antithrombotic effects of Andrographis paniculata nees in preventing myocardial infarction. AB - In 16 dogs the endothelium of the left anterior descending coronary artery was injured mechanically. Then a copper wire was inserted into the lumen as a choke of flow and the vessel was slightly compressed from outside by a constrictor. Eight dogs had been treated beforehand with a preparation of flavone extracted from the root of the Chinese medicinal herb Andrographis paniculata (TFAP). In the control group, saline solution was given, the epicardially recorded ST segment started to elevate within 15 minutes, the platelet aggregation rate and the plasma levels of TXB2 increased rapidly, whereas the level of 6-k-PGF1 alpha remained stable. Platelet cGMP rose continuously; however, platelet cAMP rose only at 60 minutes. Histological findings confirmed the occurrence of arterial thrombus and myocardial necrosis. Contrariwise, in the pretreated group there was no elevation of the ST segment, plasma 6-k-PGF1 alpha and platelet cAMP were increased, the production of TXB2 and aggregation of platelets were inhibited, and no thrombus or myocardial infarction was induced. All data suggest that TFAP might promote the synthesis of PGI2, inhibit the production of TXA2, stimulate the synthesis of cAMP in platelets, impede aggregation of platelets, and thereby prevent the formation of thrombi as well as the development of myocardial infarction. PMID- 1935362 TI - The first symposium on burn shock. PMID- 1935363 TI - [Simplified impression technique for the IMZ antirotational implant system]. PMID- 1935364 TI - [Immediate single implantation. A suitable technique using IMZ and dura mater]. PMID- 1935365 TI - [Nicholas Dubois de Chemant and the use of porcelain in dentistry]. PMID- 1935366 TI - [Trauma to permanent incisors in the child and adolescent]. PMID- 1935367 TI - New monoclonal antibody against human cervical carcinoma with diagnostic and therapeutic potential. AB - A new murine monoclonal IgG3 antibody (Mab 1H10) was developed with specificity for human cervical carcinoma and several other tumor types. Antibody reactivity against a panel of tumor cell lines was examined by indirect immunofluorescence and quantified by flow cytometry. Mab 1H10 reacted with cervical, colorectal and bladder carcinoma cells and to a lesser extent melanoma and hepatocellular carcinoma cells but did not react with human fibroblasts, lymphocytes or RBCs. Mab 1H10, as assessed by immunohistochemical staining, bound 40/97 cervical carcinoma tissue samples, 8/16 colorectal carcinoma samples as well as a population of osteogenic sarcoma and lung, ovarian and bladder carcinoma tissues. Mab 1H10 did not react with any normal tissue or cell samples tested including cervix, ovary, breast, liver, colon, bladder, lung, spleen, cerebrum, lymphocytes or RBCs. Mab 1H10 may be useful for the targeting of drugs, toxins or radioisotopes to cervical carcinoma in humans. PMID- 1935369 TI - Effect of glucose concentration, agar, and amount of inoculum on the 6.5% sodium chloride tolerance test for presumptive identification of enterococci. AB - The 6.5% NaCl tolerance test is simple and commonly used for presumptive identification of enterococci; however, it is not strictly standardized. The effect of glucose concentration, types of media and the size of inocula on the growth of enterococci have been evaluated. The results showed that broth was superior to agar media for enterococcal growth at any amount of inoculum. The media containing 1.0% glucose also showed superiority to media containing 0.1% glucose. It is suggested that broth containing 1.0% glucose be the medium of choice for 6.5% NaCl tolerance test. PMID- 1935368 TI - Diagnostic value of measuring BCG sonicate antigen and anti-BCG antibodies in the cerebrospinal fluid and blood of patients with tuberculous meningitis. AB - Fourteen cerebrospinal fluid (CSF) and paired blood samples were obtained from patients with tuberculous meningitis, seven with positive culture and seven clinical/laboratory diagnosis. Another 14 paired specimens served as control, including 7 infectious meningitis and 7 non-inflammatory neurological diseases. Four groups were thus classified, including confirmed and suspected patients, and controls with infectious meningitis and neurological diseases. Measurements of Bacillus Calmette-Guerin (BCG) sonicate antigen and IgG antibody were performed using enzyme-linked immunosorbent assay. Generally, CSF BCG sonicate antigen level and anti-BCG sonicate antibody of patients with tuberculosis meningitis were higher than in control groups; greater antigen levels were found in confirmed patients than in non-inflammatory subjects (p less than 0.05), and in suspected patients than in infectious and non-inflammatory subjects (p less than 0.05 and p less than 0.01). For serum anti-BCG sonicate levels, confirmed patients had higher antibody value than non-inflammatory subjects (p less than 0.05). To conclude, detection of high levels of both BCG sonicate antigen and antibody in CSF and blood samples shows great value in the diagnosis of tuberculous meningitis. However, given the limited samples of the current research, more data are needed to elucidate the sensitivity and specificity of such tests. PMID- 1935370 TI - Protease-like sequence in hepatitis B virus core antigen is not involved in the cleavage processes of core protein in Escherichia coli. AB - A DNA fragment, coding for hepatitis core antigen (HBcAg), was amplified by polymerase chain reaction and inserted into a lambda PL promoter-derived expression vector. The recombinant plasmid was transformed into Escherichia coli and proteins produced after heat induction were analyzed. In addition to the 21 kDa HBcAg protein, several smaller related polypeptides, particularly one of 17 kDa in size, were also detected with rabbit anti-HBcAg antiserum. Whether the protease-like sequence of core protein involved in the self-cleavage process to form the 17 kDa polypeptide was investigated by a deletion experiment. Our results with a mutant in which 7 amino acids of the conserved protease-like region in the core protein have been deleted suggest that the cleavage does not depend on the presence of these protease-like sequence. In addition, the core protein synthesized from in vitro translation reaction was not cleaved. Core particles from E. coli lysate were purified by sucrose and cesium chloride density gradient centrifugations and subsequently treated with 0.2% of SDS and 0.2% of beta-mecaptoethanol. Immunoblotting analysis, however, did not reveal any conversion of the 21 kDa protein to smaller ones. In conclusion, our results suggest that the protease-like domain at the N-terminus of the core protein does not contain intrinsic autocleavage activity, nor could the HBcAg be converted to smaller antigens by detergent treatment. PMID- 1935371 TI - Human T-lymphotropic virus type I genome in adult T-cell leukemia/lymphoma. AB - The proviral DNA of human T-lymphotropic virus type I (HTLV-I) was examined in 8 patients with adult T-cell leukemia/lymphoma (ATL/L) by Southern blot analysis. Judging from the number of bands containing viral DNA sequences in tumor cells, one and three copies of proviral genome were detected in 7 and 1 cases, respectively. The proviral genome in 1 case contained variant PstI sites and a single defective provirus which lost 5' LTR, gag and a part of pol genes was found in 2 cases. However, the pX region was detected in both of 2 latter cases by using the polymerase chain reaction. The results indicate that not all tumor cells from ATL/L yield infectious viruses and also support that the product of pX region may contribute to the tumorigenesis of HTLV-I. PMID- 1935373 TI - [Compensation of anesthesiologic services of the surgical staff in hospitals with anesthesia departments]. PMID- 1935372 TI - [Comment on "On the future of the 'field of surgery' and surgeons-- rise or decline of surgery?" by W. Muller-Osten]. PMID- 1935374 TI - [Postage stamps honor great physicians in emergency care]. PMID- 1935375 TI - [Malignant thyroid diseases--the value of classification for decision making]. PMID- 1935376 TI - [The current therapy plan in differentiated thyroid gland cancer]. PMID- 1935378 TI - [Special tumor biology and surgery of C-cell carcinoma]. PMID- 1935377 TI - [The current therapy plan in highly malignant thyroid tumors]. PMID- 1935380 TI - [Spontaneous pneumothorax--considerations on etiology and therapy]. AB - A retrospective analysis of all patients, who were treated for spontaneous pneumothorax during a ten year period from January 1st 1978 to December 31st 1987 at the Dept. of General Surgery at Kiel University (n = 140) is presented. In January/February 1990 these patients were interviewed by telephone (n = 92). There were 77% males (n = 108) and 23% females (n = 33), ratio 3:1. 131 patients had a unilateral pneumothorax, the right side was afflicted in 60% (n = 78), the left side in 40% (n = 53). A bilateral pneumothorax occurred in 19% (n = 18). 96 cases were treated for the first episode of which 95 received an intercostal drainage. Only in 65% (n = 62) the lungs reexpanded, the rest of the patients had to be treated thoracoscopically or were operated. Among those patients, who were treated exclusively by intercostal drainage, 40% (n = 25) had a recurrence and 14 of these had to be operated later. The long-term results after operation (wedge resection and/or parietal pleurectomy) were excellent with regard to recurrence rate and general health (97% almost or completely free of complaint) irrespective of the kind of operation that had been performed. The portion of smokers was 78% (n = 56) of the males and 40% (n = 8) of the females, which seems to be much higher than in the comparable groups of the general population. PMID- 1935379 TI - [Coincidence of non-medullary thyroid cancer and hyperparathyroidism]. AB - Hyperparathyroidism (HPT) and non-medullary thyroid carcinoma are not related by a common embryologic origin. In a 5-years period (1985-1989) 163 patients were operated for HPT at our hospital. Of these, 54 patients had concurrent thyroid disease, which was operated simultaneously. In 6 cases, thyroid carcinoma was found, e.g. 3.7% of all patients. This prevalence compares well to reports of different authors in the literature. The most probable explanation is the early diagnosis of asymptomatic occult papillary carcinomas; this was true in 4 of our 6 patients with thyroid malignancy. PMID- 1935381 TI - [Results of transverse tracheal resection in post-intubation tracheal stenoses]. AB - Tracheal problems in form of stenosis and malacia are a calculated risk of long term tracheal intubation. Results with conservative treatment of such problems by bougienage, laser therapy, biopsy, cryotherapy, local steroids, tracheal stenting, and tracheostomy are not satisfactory in a higher percentage of cases. Resectional therapy of benign tracheal lesions has become an established technique, which combines excellent functional results with a low complication incidence. We have treated 40 patients of 17 to 76 years of age with postintubation tracheal lesions by cross resection of the affected segment. Of these patients 40% had received conservative therapeutical steps preoperatively. The mean resection length was 3.0 cm (1.5 to 6.5 cm). The perioperative morbidity was 7.8%, mortality was 2.5%. 85% of the patients operated between 1970 and 1989 were reached for a follow-up examination with x-ray, pulmonary function test and endoscopy. The patients subjective satisfaction with the operative result was good in 85%, minor in 12% and less in 3%. The objective investigations proved very good results in 90%. Our experience confirm the good results of other authors and recommend the resection treatment for cases of postintubation tracheal lesions. PMID- 1935382 TI - [Anatomic variations in the course of the left hepatic artery. A problem for systematic lymphadenectomy in gastrectomy or proximal stomach resection before stomach tube formation]. AB - In 21 patients resected for gastric or esophageal malignancy an aberrant left hepatic artery from the left gastric artery was found. The study shows that in systematic lymphadenectomy ligation of the left gastric artery distally from the origin can safely preserve an aberrant hepatic artery without impairment of oncological quality. Related to a control group no difference in the number of resected lymph-nodes and the operation time was observed. Postoperatively there was no problem concerning liver function and surgical morbidity. In real-time sonography the aberrant artery could be postoperatively seen precisely in 19%, but duplex signal was found in 63%. Limited visualization in sonography may be caused by technical problems due to anatomy and overlying air from small-bowel reconstruction after gastrectomy. PMID- 1935383 TI - [Complications caused by use of balloon catheters in arterial thrombembolectomy]. AB - Complications related to balloon catheter thrombembolectomy in 717 cases of arterial occlusion occurred in 4.3% (= 31) and are classified in 6 groups: 16 perforations resp. ruptures (2.2%), 2 AV-fistulas (0.3%), 10 dissections (1.4%), 3 aneurysms (0.4%), intimal lesion and catheter failure. Inadequate handling is probably responsible in the majority of cases. Intraoperative angiography usually permits to recognize the complication and displays the details required for additional procedures. PMID- 1935384 TI - [Spontaneous rupture of the arteria hepatica propria]. PMID- 1935385 TI - [Adenocarcinoma of Meckel's diverticulum. Case report with literature review]. PMID- 1935386 TI - [Torsion of the omentum or appendix epiploica--rare causes of acute abdomen]. PMID- 1935388 TI - [Development of primary treatment of breast cancer 1975-1988 in German language countries]. PMID- 1935387 TI - [Dynamic axial gliding cap--a new system for endoprosthesis replacement of the hip joint. Introduction and initial experiences]. PMID- 1935389 TI - [The emergency physician in charge--chance and risk for the surgeon from the viewpoint of professional politics]. PMID- 1935390 TI - [Current legal aspects of transfusion medicine. Work distribution, autologous blood donation, refused consent, education]. PMID- 1935391 TI - [Guidelines for chief physician contracts]. PMID- 1935392 TI - [The concept of ambulatory surgery exemplified by inguinal hernia operation]. PMID- 1935393 TI - [Ambulatory surgery in pediatric surgery]. PMID- 1935394 TI - [Ambulatory surgery in venous surgery]. PMID- 1935395 TI - [Double stapling suture anastomosis in deep anterior rectum resection. Experiences and results]. AB - Between 1.1. 1984-31.12. 1989, 263 rectal carcinomas were operated at the Department of Surgery, St. Veit/Glan. The resection rate was 68.4%, the excision rate was 27.8%, other procedures were carried out in 3.8%. Staple devices were used for all anastomoses following rectum resection. Whenever technically possible, the single-stapled procedure was used (EEA, ILS). For difficult or very low anastomoses, the double-stapled technique (DST) was utilized. The DST was employed in 47 cases. This approach contributed essentially to a relatively high resection rate at our department. PMID- 1935396 TI - [One-stage surgery of high trans- and supra-sphincter anal fistula using primary fistulectomy and occlusion of the internal fistula ostium. A prospective study of 169 patients]. AB - In a prospective study on 169 patients with a so-called high fistula-in-ano (147 transsphincteric, 22 suprasphincteric) the value of a sphincter-saving operation technique was assessed. This technique consists of one-stage fistulectomy as well as of drainage of the intersphincteric space by internal sphincterotomy. The site of the former primary orifice of the fistula is adapted by multiple peranally performed single stitches. The perianal part of the wound is left to heal by second intention. Post-operatively, 19 cases of suture leakage occurred (9.5% with the transsphincteric and 23% with the suprasphincteric fistula, resp.). 32 patients (19%) had to have repeated surgery because of recurrent abscess or fistula or because of suture leakage (mean follow-up 3.2 years). Anal manometry was carried out preoperatively as well as postoperatively. It revealed a decrease in anal resting and squeezing pressure of 10 to 40% with a mean about 30%. Of the patients who had not been operated on previously, an impairment of continence developed in 15% postoperatively. This percentage rose up to 40% according to the rising number of previous fistula operations. The main problem in these cases was soiling. Total anorectal incontinence for formed stool did not occur. PMID- 1935397 TI - [Results of surgical treatment of mechanical ileus of the small intestine]. AB - Between 1982 and 1988 275 patients with obstruction of the small intestine were operated. The etiology of obstruction: adhesions 48%, malignancies 26%, strangulated hernias 8%. The duration of obstruction symptoms was 3.7 days prior to hospital admission and 1.9 days from admission to operation. 78% of patients had a history of previous laparotomies, in 73% there were serious accompanying diseases. Strangulation obstruction was found in 18% of patients. Operative procedures included small bowel resection in 30%, creation of stomata in 14%, and deviation anastomoses in 12%. Postoperative complications were mainly pulmonary. Median time of hospitalization was 24 days, hospital mortality amounted to 7.6%. A low mortality was encountered especially in strangulation obstruction and after resections. Reduction of surgery induced morbidity is primarily made responsible for the good results. PMID- 1935398 TI - [Surgery of extracranial aneurysms of the carotid artery. Analysis of 8 cases]. AB - This article reviews the clinical manifestations, operative techniques, results and complications associated with the treatment of 8 aneurysms of the extracranial carotid artery encountered over a 13-year period. The etiology was atherosclerosis in 4 cases, congenital in two, posttraumatic in one and mycotic in another case. All patients were operated on because of symptomatic disease. Six patients had resection and reconstruction with end-to-end anastomosis, one with a patch of the saphenous vein. One patient had aneurysmorrhaphy and the last one had reconstruction with Gore Tex graft interposition. Two patients had a hemiparesis prior to the operation; this manifestation disappeared slowly in both patients but residual neurological deficit is still present in one of them 9 months postoperatively. One patient developed transient neurological symptomatology after the operation. We conclude that accessible aneurysms of the extracranial carotid artery can be operated with acceptable morbidity and mortality. Operative management is the treatment of choice because these lesions are attended by a high incidence of neurological complications if left untreated. PMID- 1935399 TI - [Results of endoscopic perforating vein dissection]. AB - The subfascial discision of insufficient perforating veins is considered the most effective therapeutic principle for the treatment of postthrombotic disturbances of the skin as well as for trophic disturbances caused by varicose. A new endoscopic technique allows to be sectioned them under direct view control with little trauma. In the period from November 1986 to April 1990 61 patients underwent an endoscopic sectioning of perforating veins. Perforating veins have most frequently been separated in the area of the Cockett group (153), the 24 cm perforating vein (74) and in the area of the Boyd group (63). Two patients (3.3%) with trophic disturbances of the skin in the area of the shank showed disturbances of wound healing after the operation. First results of the follow-up examination 3-37 months postoperative have proved good (45%) to very good (40%) results. Criteria, which were observed, were pains in the leg, disturbances of sensibility, swellings and relapsed varices. Only two patients proved a bad result. Insufficient perforating veins in the area of the shank were not found by one of the 61 operated patients. Referring to a staging of chronic venous insufficiency it can be said that with the exception of the two patients above mentioned there is a ranging to a more favourable stage or to a complete treating. PMID- 1935400 TI - [Foreign body in the intestinal tract with penetration into the liver]. PMID- 1935401 TI - [Gallstone ileus--prevention by individual preventive cholecystectomy?]. PMID- 1935402 TI - [Estrogen and progesterone levels in serum and amniotic fluid before or during term labor and their relationship to uterine activity]. AB - Estradiol (E2), estriol (E3) and progesterone (P) were measured in the serum and amniotic fluid by radioimmunoassay in 73 cases, both before or during term labor. The results showed: (1) the serum E2, E3, P, E2/P and Es/P values did not differ significantly between the two groups; (2) the amniotic fluid E2 and E3 concentrations were significantly higher for women in active labor and more evident in those with normal uterine activity, but the progesterone concentration did not vary significantly among the three groups. Thus, the increase of estrogen and estrogen/progesterone ratio in amniotic fluid may be related to the mechanism of spontaneous onset of term parturition in human and as well to dysfunctional labor. PMID- 1935403 TI - [Air sac midwifery technique for shortening course of labor]. AB - Air sac midwifery technique is developed in this hospital to cut down the duration of labor (birth process). A special small sac is placed inside the ripe cervix and vagina of women of term pregnancy, and aerated slowly till a positive pressure of 16-25 kPa is reached. The cervix can be dilated to 6 to 8 cm, and the vagina 10 to 12 cm in 1 to 2 minutes. The labor course may be cut down by 8 to 10 hours, thus relieving the parturient from pain, lessening perineal laceration and perinatal mortality which is important for eugenics sake. PMID- 1935404 TI - [Color pulsed Doppler ultrasound measurement of fetal umbilical and uterine arteries blood flow for early predict of intrauterine growth retardation]. AB - The fetal umbilical and uterine arteries blood flow in 180 pregnant women (normal group and suspected IUGR group are separately 90 pregnancy) were measured by color pulsed Doppler ultrasound in this report. The predicting value for IUGR of Doppler ultrasound was comprised with that of the diagram of pregnancy and real time ultrasound. There were 39 cases of IUGR, three cases of perinatal death and 138 normal infants in total 180 pregnancy. The sensitivity, specificity and positive predicting value of fetal umbilical flow for predicting IUGR were separately 78.57%, 93.75% and 91.67%. The results suggest that Doppler ultrasound blood flow measurement can predict IUGR much earlier than the diagram of pregnancy and real-time ultrasound. Combining to use Doppler ultrasound with real time ultrasound measurement have highest sensitivity and accuracy. PMID- 1935405 TI - [Hashimoto's disease with pregnancy]. AB - That normal pregnancy, PIH and Hashimoto's were all closely related with human immunology has been reported by many authors. Six pregnant women with Hasimoto's were studied. Among them four were complicated with PIH, and one with postpartum transient hypothyroidism. MCHA and TGHA were slightly decreased in 2 cases during pregnancy and one congenital hypothyroidism happened among 6 neonates. Our data indicates that pregnancy and Hashimoto's can affect each other. PMID- 1935406 TI - [Research on karyotypic consistency between chorionic villi and fetus]. AB - In the last decade, chorionic villi sampling (CVS) has been widely accepted as a new technique in prenatal diagnosis. An inconsistency in karyotypes between CVS and fetal tissue was found in clinical practice, although the chorionic villi and the fetal tissues were from the same fertilized ovum. Karyotypes from direct chromosomal preparation of chorionic villi and cultured fetal tissues in 52 artificial abortion samples were compared. Results showed two cases with karyotypic inconsistency: (1) 46, XX/46, XY in the chorionic villus direct preparation and 46, XX in the fetal tissue; (2) 46, XY in the direct preparation of chorionic villi and 45,XY, t (15q21q) de novo in the fetal tissue. Our research demonstrates that karyotype from chorionic villus direct preparation does not always reflect the fetal karyotype. PMID- 1935407 TI - [Cyclic endometrial changes, ovulation and serum estradiol and progesterone levels in female sterility]. AB - Serial endometrial biopsies and determinations of serum E2 and P levels by radio immunoassay were performed in 11 women with idiopathic sterility. B ultrasound was employed to monitor the development of follicles and the exact ovulation day. In 9 cases ovulation was observed and normal endometrial changes according to Noyes' criteria with normal cyclic changes of E2 and P levels were present in only 4 cases. 5 ovulated from follicles of smaller size and the secretory phase of the endometrium was delayed. The asynchronous development of endometrium associated with lowered E2 in the follicular phase was deemed to interfere with implantation even in the presence of normal fertilization. Two patients failed to ovulate on account of atretic follicle in one and LUFS in the other. The authors suggest that in idiopathic sterility, especially in the presence of atypical endometrium on the first day of menstruation the E2 levels in the follicular phase and endometrial status on the 3rd-4th day after ovulation should be given due attention. PMID- 1935408 TI - [Stripping technique in radical pelvic lymphadenectomy]. AB - An improved pelvic lymphadenectomy technique by stripping of the lymphatic tissue was introduced. From January to December, 1989, this technique was performed in 43 patients, consisting of 36 cases of cervical carcinoma, 5 cases of endometrial carcinoma and 2 cases of ovarian carcinoma. The mean operative time was 12.6 minutes for the left pelvic lymphadenectomy and 13.3 minutes for the right side. The bleeding during operation was insignificant and no severe complication was observed. PMID- 1935409 TI - [Endometrial polyps. A clinico-pathologic analysis]. AB - A clinico-pathologic analysis of 92 cases of endometrial polyps was carried out and the endometrium adjacent to the polyps was studied in 69 cases. Most endometrial polyps occurred between 30-60 years of age, often accompanied by abnormal uterine bleeding. Immature endometrial polyp was the most common pathologic type (65.0%), usually associated to some extent with hyperplastic changes. Cystic glandular hyperplasia was observed in nearly half of the polyps obtained from postmenopausal patients. Different histologic pictures were found in the adjacent endometrial tissues, of which 59.4% showed normal changes. PMID- 1935410 TI - [Selenium concentrations in serum, hair and tumor tissue from patients with ovarian tumors]. AB - Selenium (Se) concentration was determined in 150 samples of serum, 135 samples of hair and 96 samples of ovarian tissue from patients with malignant or benign ovarian tumors and normal subjects. The serum Se level in patients with malignant ovarian tumors was significantly lower than that in patients with benign ovarian tumors and normal subjects. No difference of Se concentrations of hair among different groups was observed. Se level in malignant ovarian tumor tissue was significantly higher than that in benign ovarian tumor tissue and normal ovarian tissue. The low serum Se level in patients with malignant ovarian tumors was probably the result of protective migration of Se from blood to the cancer tissue. PMID- 1935412 TI - Sunspots and hip fractures. AB - In this paper a remarkable statistical link between sunspot cycles and prevalence of hip fractures in the elderly is shown. Hip fractures in old people are due to: 1. increased bone fragility for metabolic bone disease; 2. increased propension to fall. Though it is obvious that a correlation does not imply any causal relationship, reasonable conjectures can be allowed. The hypothesis of an 11-year cyclic variation of ultraviolet radiation as a cause of hip fractures is untenable; one may better assume that solar flares can negatively influence the nervous postural regulation leading to a greater propensity to accidental falls. PMID- 1935411 TI - [Effect of levonorgestrel intrauterine device on human endometrial estrogen and progesterone receptors]. AB - Estrogen and progesterone cytoplasmic receptors (ER, PgR) were determined by radiochemical DCC technique in the endometria of 16 normal women at before child bearing age and 6 to 9 months after LNG IUD insertion. The study showed that both ER and PgR were reduced significantly after LNG IUD insertion (P less than 0.01). The decrease of ER and PgR might play an important role in gland reduction and endometrial atrophy. It may be one mechanism of the contraceptive effect and the cause of anemia or spotting between menstruation during the course of LNG IUD insertion. PMID- 1935413 TI - Circannual rhythms in the activity of the parathyroid gland and ultimobranchial body cells of the frog Rana temporaria (Anura, Amphibia). AB - The annual activity of the parathyroid gland cells and those of the ultimobranchial body cells of the frog Rana temporaria is quantitatively investigated by a morphometric study. A cosinor analysis shows a periodic succession of different parameters. The secretory activity of the parathyroid cells starts after a maximal value of external temperature in July. This activity is followed by an increase of plasma calcium which seems to induce the activity of the ultimobranchial cells. PMID- 1935414 TI - Timing of parturition in the rat: an analysis of successive births. AB - To determine whether consecutive parturitions within individual rats are likely to occur around the same time of the 24h day, female rats mated prior to ovulation and maintained on a LD 12:12 photoperiod, were observed over either two or three parturitions. A subgroup of females was placed on constant light during the second gestation in order to determine the role of photoperiod in the temporal synchronization of consecutive births. The major findings were 1. individual females tended to give birth around the same time of the day on consecutive births so long as the photoperiod remained constant; 2. the small percentage of births occurring during darkness, the less-prevalent time of the photoperiod for birthing, were anomalous births for individual females; and 3. litter weight was a significant factor in predicting time of birth for females, but this effect interacted with photoperiod. These data elucidate the importance of knowing previous birth time, litter weight, and photoperiod on predicting the time of parturition in the rat. PMID- 1935415 TI - Circadian chronobiology of epilepsy: murine models of seizure susceptibility and theoretical perspectives for neurology. AB - As an integrative discipline in physiology and medical research, chronobiology renders possible the discovery of new regulation processes regarding the central mechanisms of epilepsy. In this context, the temporal fluctuations of seizure susceptibility rhythmometrically detected tend to demonstrate 1. that tonic clonic events are circadian stage-dependent processes whose temporal characteristics (i.e. MESOR, amplitude, acrophase) and clinical parameters (e.g. neurological components, severity of motor discharges) are predictable on the basis of mathematical models, and 2. that the generalized epileptic onsets may respond to telencephalic integrations modulated by centrencephalic circadian processes of vigilance. Considering the data model assumed for our rhythmometric analyses, the circadian psychophysiological patterns of epilepsy also express dynamic biologic systems which reveal some intermodulating endogenous processes between vigilance and seizure susceptibility. The new chronophysiology investigations considered at a rhythmometric level of resolution suggest several heuristic perspectives regarding 1. the central pathophysiology of epilepsy and 2. the behavioral classification of convulsive events. Such circadian studies also show that chronobiology raises some working hypotheses in psychophysiology and permits the development of new theoretical concepts in the field of neurological science. PMID- 1935416 TI - Patterns of daily allocation of sleep periods: a case study in an Amazonian riverine community. AB - Few works already carried out have examined the relative role of genetic and external factors on the determination of the rhythmicity of the human sleep/wake cycle. In order to make a preliminary approach in this field, we investigated the diversity of patterns of allocation of sleep periods among 29 families living at the Combu Island, a socioculturally very homogeneous human group of the Brazilian Amazon. The individuals were interviewed through a questionnaire designed by Horne and Ostberg (1976), with the language of the questions adjusted to the way of-life of the riverine people. A large predominance of the morning type was observed (95.35%), what constitutes a strong deviation in relation to other populations studied, suggesting the occurrence of a masking effect. The individual scores presented a positive correlation with the age (r = 0.31; p less than 0.01), and a significant intersexual difference was also verified (t = 3.08; p less than 0.01). This intersex difference is explained, in part, by analyzing the socioeconomic patterns of the community. The offspring/parent regression of the individual scores indicated a low dependency between genitors and their direct descendents (p greater than 0.7), and the estimative of heritability obtained (0.14) is artificial, since the offspring/mother and offspring/midparent regression coefficients were negative. Statistically non-significant coefficients of correlation and/or regression showed a highly randomic populational distribution of scores for the Horne-Ostberg's test. Such findings suggest that the intensity of the masking over the sleep/wake cycle varies among human populations, and that the individual tendency towards morningness/eveningness is strongly related to sociocultural factors. PMID- 1935417 TI - Enzyme mimics. AB - 'Two is better than one' in cooperating systems. Synthetic ditopic host molecules have been constructed from cyclodextrins and from synthetic hydrophobic cavities bridged with simple connectors or with catalytic groups. These host molecules show very strong binding of appropriate substrates, and selective catalysis. A cyclodextrin bis-imidazole shows bifunctional catalysis of the cleavage of a cyclic phosphate that is simultaneous, judged from isotopic studies. The best geometry is consistent with mechanistic evidence on the preferred mechanism for such bifunctional catalysis. Certain polar compounds bind to a still unidentified cellular receptor and induce differentiation of malignant cells. Ditopic drugs that have been designed and synthesized bind strongly to two receptor sites and induce cancer cell differentiation at low concentrations with few side-effects. Clinical results with these compounds are already promising in a few cancer patients. PMID- 1935418 TI - Binding of antibiotics to DNA. AB - The DNA molecule can serve as host to numerous guest ligands, some of which are antibiotics, and almost all of which are endowed with anticancer or antimicrobial activity. Many guest ligands are quite large and complex in structure, and an array of intermolecular contacts underlie their complementarity to their macromolecular receptor. Often the process of molecular recognition involves conformational adjustments on the part of the interacting species, but the lion's share of the adjusting is demanded of the DNA helix which commonly ends up considerably distorted. Generally the lock must bend to accommodate the key. Two fundamentally different modes of binding can be identified: intercalation and minor groove-binding. The former mode is exemplified by daunomycin or actinomycin and the latter by netropsin or distamycin. Intercalation is associated with substantial extension and unwinding of the helix whereas groove binding is characterized by replacement of the spine of hydration and by lesser effects on helix geometry such as local bending. Bifunctional (or bis-) intercalation, as seen with echinomycin, causes the most far-reaching perturbations in the structure of DNA. It might even involve altered base pairing, which has been observed in complexes between echinomycin and oligonucleotides but has not yet been detected with macromolecular DNA in solution. PMID- 1935419 TI - Design of sequence-specific bifunctional nucleic acid ligands. AB - Homopyrimidine oligodeoxynucleotides have been covalently linked to intercalating agents. These bifunctional nucleic acid ligands bind to the major groove of DNA at homopurine.homopyrimidine sequences, where they form triple helices. The homopyrimidine oligonucleotide binds parallel to the purine strand of the double helix. Two hydrogen bonds are formed between bases of the oligonucleotide and the purines engaged in Watson-Crick base pairs. The intercalating agent inserts its aromatic ring at the triplex-duplex junction, resulting in a strong stabilization of the triple helical structure. Bifunctional oligonucleotide-intercalator conjugates provide new tools for a selective control of gene expression. In addition, irreversible reactions can be targeted to the oligonucleotide recognition sequence. Cleavage reactions can be induced by a copper phenanthroline chelate or an ellipticine derivative covalently linked to the triple helix-forming oligonucleotide. PMID- 1935420 TI - Conformational flexibility and protein specificity. AB - Dihydrofolate reductase is of pharmacological interest as the target for a number of useful drugs including methotrexate, trimethoprim and pyrimethamine. The binding of substrates, inhibitors and coenzymes to the enzyme has been studied by NMR spectroscopy in conjunction with site-directed mutagenesis; changes in the chemical structure of the protein or the ligand are found to have a variety of effects on both the time-average conformation and its fluctuations. These experiments have revealed a number of instances where the specificity is influenced by conformational fluctuations or equilibria. Both the substrate, folate, and the coenzyme, NADP+, have alternative modes of binding to the enzyme. The pteridine ring of folate can bind in two distinct orientations, depending on the ionization state of Asp-26. In the enzyme-trimethoprim-NADP+ complex, the nicotinamide ring of the coenzyme exists in two states, either bound to the enzyme or hanging free in solution. Analogues of the inhibitor pyrimethamine exist in two slowly interconverting conformations, both of which are able to bind to the enzyme. In all these cases the different modes of ligand binding have very similar binding energies and play a role in determining the specificity of the enzyme. PMID- 1935421 TI - Protein design: template-assembled synthetic proteins. AB - The introduction of the template-assembled synthetic protein (TASP) concept for the de novo design of proteins has provided a very powerful new tool for the construction of artificial tertiary structures. TASPs are constructed by the covalent attachment of amphiphilic secondary structure blocks to a topological template, resulting in a non-linear chain architecture of the target molecules. A key feature of this approach is that the template serves to reinforce and direct the folding of the secondary structure elements into predetermined tertiary structures. Having used stepwise solid-phase peptide synthesis (SPPS) in combination with linear oligopeptide templates in the initial stages of our research on TASPs we are now pursuing refined structural and synthetic approaches in the construction of the next generation of TASP molecules. These include the synthesis by SPPS of four-helix bundle TASPs using new cyclic templates (containing either S-S bridges or beta-turn mimetics) as well as conventional fragment condensation strategies using protected fragments. The conformational properties of these new TASPs are now under investigation, with special emphasis on the relationship between overall conformation and the nature of the topological template. PMID- 1935422 TI - Binding of peptides to proteins: an exercise in molecular design. AB - Peptides coupled to solid supports were systematically tested for binding activity with a polyreactive immunoglobulin light chain dimer by the methods of Geysen and colleagues. Once identified, peptides of progressively increasing affinity for the dimer were synthesized in milligram quantities and diffused into crystals of the protein. The three-dimensional structures of the peptide-protein complexes were determined by X-ray analysis and crystallographic refinement. Criteria for the design of ligands to fill the binding cavity in incremental stages could be formulated from the combined results of peptide scanning and crystallographic analyses. Histidine proved to be an important substituent in the binding series. It was possible to manipulate the properties of this amino acid residue to alter the structures and binding patterns of the ligands. For example, if two beta-alanine residues were added to the carboxyl end of a tetrapeptide ligand, the terminal carboxyl group formed an intramolecular ion pair with the imidazolium group (N-3) of histidine. This interaction was accompanied by cleavage of the intra molecular hydrogen bond between N-1 of histidine and the amide group of a glutamine side chain. The shape of the ligand shifted from a compact to an extended form and the mode of binding changed from a lock-and-key to an induced-fit type. The direction of entry of dipeptides of histidine and proline into the binding cavity (normally amino end first) could be reversed (carboxyl end first) by protonation of the histidine ring. PMID- 1935423 TI - Involvement of water in host-guest interactions. AB - As predicted by inhibition studies the X-ray crystal structure of the complex formed between the tetrasaccharide alpha-L-Fuc(1----2)-beta-D-Gal(1----3) [alpha L-Fuc-(1----4)]-beta-D-GlcNAc- OMe (Leb-OMe) and the lectin IV of Griffonia simplicifolia (GS-IV) shows three hydroxyl groups (referred to as the polar key) hydrogen bonded within the combining site and flanked by hydrophobic surfaces. Apart from OH-6 of the beta-D-GlcNAc unit, the six other hydroxyl groups reside at or near the periphery of the combining site. Linear enthalpy-entropy compensation is observed for complex formation with monodeoxy and other derivatives of Leb-OMe involving one of these six hydroxyl groups. Decreases in both the thermodynamic parameters (- delta H 0 and - delta S 0) are largest when a hydroxyl group is in contact with water at the periphery of the combining site. The experimental evidence indicates that the binding reactions involve very similar if not identical changes in the conformations of both the lectin and the ligands; it is therefore proposed that the enthalpy-entropy compensations arise because water molecules hydrogen bonded to the amphiphilic surfaces of the unbound oligosaccharide and the protein are more mobile (higher entropy content) and less strongly hydrogen bonded than are water molecules in bulk solution. Monte Carlo simulations of the hydration of Leb-OMe appear to support this idea. In accordance with this proposal the association of complementary amphiphilic molecular surfaces from aqueous solution is driven by the release of the water molecules from both non-polar and polar regions of the amphiphiles to form stronger hydrogen bonds in bulk water. In the case of highly amphiphilic molecules such as the oligosaccharide Leb-OMe the negative contributions to entropy change dominate positive contributions that may arise from hydrophobic effects. The GS-IV(Leb-OMe)2 complex is stabilized by the hydrogen-bonding networks involving an asparate, an asparagine and a serine residue within the combining site and the above-mentioned key hydroxyl groups. Improved packing of the molecules may also be involved. PMID- 1935424 TI - Molecular modelling approaches to host-guest complexes. AB - Host-guest interactions can be modelled as a non-bonding recognition process using long-range electrostatic forces. By using molecular isopotential maps the differences between the methotrexate-dihydrofolate reductase and folate dihydrofolate reductase complexes can be predicted. By extending the technique to molecule-molecule docking the interaction of formamide with the crown ether 18 crown-6 can be simulated with reasonable accuracy. The closely related problem of predicting the separation of enantiomers of chiral molecules by chromatography has been attempted with encouraging results. A preliminary report is presented on the progress being made towards a better model for simulating stacking arrangement of pi systems by charge distribution. PMID- 1935425 TI - Host-guest interactions in thin membranes: selective ion transport and transduction into electronic signals. AB - Synthetic receptor molecules that selectively complex with charged guest molecules can be used to transport salts through liquid membranes and to transduce chemical information into electronic signals. In both cases the receptor molecules are present in thin membranes in contact with aqueous solutions. Extreme lipophilicity of the receptor molecules is therefore required: calix crown ethers and calixspherands meet these requirements. Their synthesis and complexation properties will be discussed. In order to mimic the large rates of transport through biomembranes, thin supported liquid membranes (less than 100 microns), in which the receptor molecules are present, were investigated. The selective ion transport has been studied as a function of the experimental parameters and interpreted via computer simulations of the transport processes. The transduction of complexation into electronic signals can be achieved via the 'immobilization' of receptor molecules on the gate surface of an ISFET chip. Parameters that govern the signal transduction in multilayer systems have been studied and stimulated. PMID- 1935426 TI - Molecular self-assembly processes. AB - A logical and stepwise approach to the establishment of the concept of self assembly in the synthesis of wholly unnatural products is proposed. The approach is based on the use of irreversibly interlocked molecular systems in the shape of catenanes and rotaxanes as the vehicles through which to transfer from host-guest chemistry the knowledge and experience gained on relatively small molecules to much larger molecules including polymers in which the molecular components are reversibly intertwined. The proposal presents a manifesto for making the transformation from supramolecular to polymolecular chemistry. A number of recent template-directed syntheses of catenanes and rotaxanes are presented as examples of structure-directed synthesis, to illustrate that there are inherently simple ways of making apparently complex unnatural products from appropriate substrates without the need for reagent control or catalysis. PMID- 1935427 TI - Molecular recognition and molecular sensors. AB - Enzyme-substrate recognition provides a convenient and powerful basis on which to construct molecular sensors. In direct enzyme electrodes the rate of the enzyme reaction is transduced into a current using an electrode made of a conducting organic salt. In vivo microelectrodes designed to measure glucose have been constructed and used in the brain of the freely moving rat. Another strategy is to use enzymes that operate with NADH; the NADH can readily be oxidized on conducting organic salt electrodes. Results for the measurement of micellar equilibria involving bile acids are presented. The packed-bed wall-jet electrode provides a device of greater sensitivity; results for the measurement of femtomoles of acetylcholine obtained by microdialysis from cerebral fluid demonstrate the power of this method. The wall-jet ring-disc electrode can be used in an electrochemical immunoassay again at the femtomole level. Finally, enzyme inhibition can be used to make a sensor for toxic substances such as H2S at the p.p.m. level. PMID- 1935428 TI - The natural design of vancomycin family antibiotics to bind their target peptides. AB - The vancomycin family of antibiotics provide a rare opportunity among natural systems to study a molecular recognition process in which both the 'receptor' and the 'ligand' are relatively small molecules. Unlike the vast majority of antibiotics, in the vancomycin family the antibiotic performs the role of the receptor. All members of the family are covalently cross-linked heptapeptides that contain a variety of glycosidic modifications. Their site of action in bacterial cell walls is modelled by simple dipeptides and tripeptides. NMR experiments have been used to characterize the binding of these species through the study of both the complex and the free components. In unbound antibiotics conformational freedom is observed in regions of the molecule not severely restricted by covalent linkages. On binding of the ligand much of this conformational freedom is lost and the hydrophobic side chains of the antibiotics reside close to the intermolecular hydrogen-bonding interactions, thus shielding these interactions from the solvent. The charged amino groups of the N-terminus and disaccharide region of vancomycin are orientated not to optimize intermolecular electrostatic interactions but rather to retain solvation. This causes further hydrophobic faces to be presented to the ligand. Removal of saccharide units from the antibiotics leads to small losses in binding energy but may have considerable influence on the selectivity of the antibiotics. Specific dimerization through the non-ligand-binding faces of ristocetin is observed at millimolar concentrations. The geometry of the dimeric complex enables a close approach of the ligand carboxylate anion and the charged amino group of the novel sugar, ristosamine. PMID- 1935429 TI - Clefts as receptor and enzyme analogues. AB - Synthetic receptors for small biological targets have become a popular research topic in molecular recognition. This paper discusses the optimal functional group complements and the scaffolds that are ideal for such purposes. Specifically, remote steric barriers are used to control the conformation of (that is, to preorganize) hosts derived from acridine skeletons, triaryl benzenes and related systems. These structures separate entropic effects from enthalpic effects and show that entropy is an important contributor to high affinity. In a comparative study lactams are shown to be superior to imides in their capacity for self association. Imides are shown to have higher affinity than lactams for adenine derivatives because of the presence of an unconventional hydrogen bond. Finally, preorganization in the context of chemical catalysis is demonstrated in two systems, one involving hemiacetal cleavage and a second involving a self replicating system. PMID- 1935430 TI - [Image diagnosis of polypoid lesions of the gallbladder]. AB - Between 1980 and 1990, 120 cases of polypoid lesions of the gallbladder (GBPL), confirmed surgically and pathologically, were evaluated comprehensively with each kind of image examinations. 110 cases of B-US data were dealt with multiple stepwise regression analysis, and three carcinoma risk factors (size & location of the lesion, age of the patient) were found. The results of Mahalanobis' discriminant analysis showed that the conformity rates of retrospective test (80 cases) and prospective test (30 cases) were 94% and 90%, respectively. In addition, we put forward our own clinical classification of GBPL according to the surgical and pathological data and the need of clinical practice. PMID- 1935431 TI - [Percutaneous cholecystolithocenosis. Report of 421 cases]. AB - Modified percutaneous cholecystolithocenosis (PCLC) was performed in 421 cases of gallstones. The advantages of this operation included less traumatic, fast convalescence, few complications, and thorough stone clearing. It was suitable for in operatable elder patients. The procedure was safe, and did not produce any incidental injury to the internal organs. The successful rate was 100%. 122 cases were followed up cholecystographically. Gallstones disappeared in 96.8% of the patients and gallbladder function was improved. Follow-up of 57 cases after extracorporeal shock wave lithotripsy (ESWL) showed that gallstones were broken into small pieces which are feasible to pass through the gallbladder tube. PMID- 1935432 TI - [A study on factors influencing the stability of total nutrient admixture]. AB - To study the stability of total nutrient admixture, glucose, amino acid, fat emulsion, electrolyte, and other nutrients in different combinations and concentrations were admixed and infused into 16 3-liter polyvinyl chloride bags, which at last were stored at 4 degrees C, 22-25 degrees C, 32 degrees C, respectively. Samples were inspected at 0, 12, 24 and 48 hours. The results showed that the admixture was stable when total concentration of mono cation was lower than 150 mmol/L, Mg2+ less than 3.4 mmol/L, and Ca2+ less than 1.7 mmol/L, stored at 4 degrees C for 48 hours, or at 22-25 degrees C for 24 hours. We conclude that PVC 3L container is safe for storage of TNA at least within 24 hours. PMID- 1935433 TI - [Clinical study of liver alveolar hydatid disease]. AB - 113 patients with liver alveolar hydatid disease confirmed by laparotomy were analyzed. The patients were found in epidemic areas; this factor was considered in the diagnosis of the disease. Digestive tract symptoms and right epigastric mass, usually as firm as a stone, were the commonly seen clinical features. Many patients suffered from light anemia and hepatosis. Casoni test and PPA-ELISA were positive in 85.84% and 100% of the patients respectively. B-ultrasonography was most useful diagnostic means with characteristic wave shape and figure, and the diagnosis was confirmed by laparotomy in 93.18% of the patients. Most lesions were single large-well-circumscribed masses (53.93%); nodular lesions and mixed type lesions were found in 29.2% and 16.81% of the patients respectively. Radical resection was performed in 20 patients (17.7%), 85% of the patients were cured. Symptoms were relieved in 75% of the late-stage patients undergoing tumor excavation and drainage plus pharmacotherapy. Patients treated by albendazole, medicinal herbs, or both showed similar effective rates of 86.37%, 90%, and 88.23%, respectively (P greater than 0.05). PMID- 1935435 TI - [A new instrument for percutaneous biopsy of bone and joint]. AB - A newly designed percutaneous biopsy instrument has been used clinically. The instrument consists of parts of clamping, aspiration, spooning, cutting and rotational scraping in accordance with the pathological tissue or specimens. This instrument is called CCACS system. In use, the instrument with its protective cannula is punctured into the objective tissue percutaneously. Then a suitable part of the instrumental components is chosen and put through the cannula into the lesion to get sample, repeatedly if necessary. The system was used to take specimens from 61 patients with tumours (malignant 23, benign 28) or inflammations (10) of torso, limb bone or joint. It was successful in 59 patients (96.72%) and failed in 2 patient (3.28%). PMID- 1935434 TI - [Gastrectomy preserving pylorus and pyloric vagus]. AB - Gastrectomy preserving pylorus and pyloric vagus was done in 32 cases to preventing complications caused by conventional gastric resection. This operation, similar to Billroth I (B-I) and Billroth II (B-II) in reducing acidity, was effective in preventing reflux and dumping syndrome. But the results of this operation were better than those of B-I and B-II according to postoperative gastric emptying test, fat and protein digestion, gastric biopsy, body weight, and patients' general conditions. PMID- 1935436 TI - [Long-term pathological findings of cerebral arteriovenous malformation after embolization]. AB - Cerebral arteriovenous malformation was resected after embolization with Aron alpha and ZT plastic in 2 cases. Pathological examination in one patient revealed intravascular residual foreign-body giant-cell reaction and slight chronic inflammation in the adjacent parenchyma of the brain tissue 1.5 years after embolization. The other 1 patient was treated with embolization 4.5 years ago. No pathological changes were found either in the vessels or in the brain tissue. It is indicated that chronic inflammation after embolization with cyanoacrylate disapproved several years later. PMID- 1935437 TI - [Abnormal systemic artery originating from descending aorta to normal basal segments of left lung. Report 2 cases]. AB - Two patients with a large abnormal systemic artery originating from the descending aorta several centimeters above the diaphragm to the four basal segments of normal left lower lobe (without cystic change like that found in the bronchopulmonary sequestration) were treated. No pulmonary artery was found to supply the basal segments. The patients suffered from repeated hemoptysis. In one patient the abnormal artery was incidentally found during bronchial arteriography. Lower lobectomy was performed in the two patients. Microscopic examination of specimens revealed some dilated small blood vessels with extremely thin walls and their rupture may be the cause of hemoptysis. Abnormal systemic artery must be suspected if hemoptysis or local murmur during chest examination cannot be explained by other conditions, and care must be taken not to injure the artery in isolating pleural adhesion and pulmonary ligament. PMID- 1935438 TI - [Hepatectomy with Nd:YAG laser: an experimental and clinical study]. AB - We conducted an experimental and clinical study of hepatectomy with Nd:YAG laser. The results showed that cutting effect artificial sapphire contact Nd:YAG laser scalpel was better than that of quartz fiber contact and noncontact Nd:YAG laser. The tissue damage was minimal in the former group whereas, the blood loss was similar in both groups. Seven patients were operated on, with quartz fiber and 12 with artificial sapphire laser scalpel. No complications were related to the use of laser. We consider that partial liver resection can be performed effectively with artificial sapphire contact Nd:YAG laser scalpel because of its better cutting, coagulation effects, and less tissue damage. PMID- 1935439 TI - [Autogenous transplantation of pedicle iliac crest epiphysis to epiphyseal defect of joint. An experimental study in puppy]. AB - In 24 immature dogs, autogenous iliac-crest apophyseal graft was transplanted into the defect created in epiphysis of the femoral head. The dogs were divided into 2 group. In the group I, the graft was pedicled with circumflex iliac vessels. In the group II, the same technique was used without pedicle. All the animals were followed up for 1-6 months. The specimens were studied by macroscopic, histological, histochemical and electron-microscopical examinations. The examinations revealed that the pedicle grafts survived with good remodelling in joint defects. The ossification of the iliac-crest physis seemed to be normal. The superficial part of the graft did not undergo ossification, and the histologic structure of the graft was similar to the articular cartilage of the femoral head. It is possible to reconstruct a joint surface and to repair the epiphyseal defect of joint. PMID- 1935440 TI - [Inhibitory effect of Chinese herb medicine zhuling on urinary bladder cancer. An experimental and clinical study]. AB - Inhibitory effect of Zhuling (Grifola umbellata pilat) on urinary bladder cancer was determined experimentally and clinically. The results showed that zhuling inhibited significantly the induction of bladder cancer in rats exposed to N butyl-N-(4-hydroxybutyl) nitrosamine (BBN), decreasing from 100% (18/18) in control group to 61.1% (11/18) in zhuling (P less than 0.01). Zhuling was given to 22 patients with recurrent bladder cancer after TUR or partial cystectomy. The patients were followed up for 12 to 38 months (average 26.5 months). Bladder cancer recurred in seven of the patients with a longer recurrence interval (19.2 months) after medication than before medication (P less than 0.05). The remaining 15 patients had no recurrence. The mechanism of Zhuling is discussed. PMID- 1935441 TI - [The characteristic electroretinogram anomalies in age-related macular degeneration]. AB - The color stimulated electroretinogram (ERG) was found abnormal in 104 eyes of 64 cases of age-related macular degeneration (AMD). The number of a-wave troughs with dark adapted red stimulation decreased in 69 eyes, of which 27 eyes also showed diminished a- and b-waves under dark and light adaptation. Among the remaining 35 eyes that demonstrated no decrease in the number of a-wave troughs, there were 6 eyes with a- and b-wave diminution under dark and light adaptation. The findings indicated that the ERG anomalies in AMD were detected more readily with dark adapted red stimulation, particularly evident in the wet type of AMD, thus conducive to the judgement of visual impairment and prognosis. PMID- 1935442 TI - [Primary color P-VEP in diabetic retinopathy]. AB - 148 normal eyes and 123 eyes of diabetic retinopathy patients were examined the red, green, blue primary color and black/white P-VEPs, with the conclusion that the latencies of P100 were significantly delayed in the diabetic group, particularly that of the blue color, which was also in positive correlation with the level of blood sugar and the duration of diabetes. The consistency of blue P VEP with fluorescein angiographic examination in diabetic retinopathy was good, and the abnormality ratio of the former (73.0%) was higher than that of the latter (60.2%). The results indicated that S-wave cones were damaged more readily than were L-wave cones, and the blue P-VEP was sensitive in monitoring the injury to visual function in diabetes. PMID- 1935443 TI - [The pattern electroretinogram in diabetic retinopathy]. AB - The pattern electroretinogram (PERG) was examined in 79 eyes (47 patients) of diabetic retinopathy (DR), with the results that the amplitude of b-wave was significantly reduced early in the subclinical phase of DR, and the latency was lengthened from stage I on. The value of PERG in the early functional diagnosis of DR was discussed. PMID- 1935444 TI - [Quantitative evaluation of flicker ERG wave forms in low vision patients]. AB - Flicker ERGs of 30 Hz were recorded for 46 eyes (23 cases) of low vision, including 38 eyes with retinal diseases and 8 eyes with optic neuropathy, and also for 39 normal eyes. The abnormality ratios were compared with regard to (1) the directly measured peak to peak amplitude and pseudo-phase, and (2) the amplitude and phase of fundamental response component (30 Hz) by discrete Fourier transform (DFT). All eyes with optic neuropathy showed normal flicker ERG, while the abnormality ratios of the directly measured pseudophase and the phase by DFT were 60.9% in 28 eyes and 82.6% in 38 eyes with retinal diseases respectively, the difference being statistically significant (P less than 0.05). These findings suggest that DFT for flicker ERG is more useful in quantitative evaluation of the retinal function. PMID- 1935445 TI - [Oscillatory potentials of the electroretinogram in the domains of frequency and time]. AB - The dark and light adapted ERGs of 36 normal eyes (20 subjects) were analyzed with the Fourier frequency spectrum. The oscillatory potentials (OPs) were isolated from the ERGs with a proper bandpass. The amplitudes and implicit times of the wavelets, the accumulative amplitude and area, the dominant frequency and energy, and the total energy of OP1 to OP4 were determined. Comparison of the coefficients of variation (CV) showed that the CV of implicit times was the least, while the CV of amplitudes, dominant energy and total energy were larger. Furthermore, the CV of parameters under light adaptation were smaller than those under dark adaptation. PMID- 1935446 TI - [Pattern ERGs recorded with a self-made gold plated electrode in normal subjects]. AB - PERGs were recorded with a self-made gold plated electrode in normal subjects. The latency and amplitude of b wave were 48.7 + 1.6 ms and 3.7 + 0.9 uv respectively. The amplitudes of b wave and negative after-potential from the cornea-ear lead were larger than those from the cornea-temporal or the cornea forehead lead, but no statistically significant differences were noted among the latencies from the 3 leads. The gold plated electrode is believed suitable for recording the PERG, and placement of the reference electrode on the ipsilateral earlobe recommended. PMID- 1935447 TI - [Hyperbaric oxygen treatment for cystoid macular edema secondary to retinal vein occlusion]. AB - A prospective study was made to estimate the effect of hyperbaric oxygen (HBO) on 14 eyes of cystoid macular edema (CME) secondary to retinal vein occlusion. The visual acuity was improved 2-6 lines (average 3.6 lines) after the treatment, while the control group of 12 cases showed little improvement. The therapeutic effect was stable, however, fluorescein angiography showed no leakage reduction from the perifoveal capillaries, or visual function was enhanced prior to eventual improvement in the fundus. Since HBO therapy has few contraindications nor side effects, it is an effective modality in the treatment of CME. PMID- 1935448 TI - [Cilioretinal arteries under fundus fluorescein angiography]. AB - Cilioretinal arteries were found in 825 (40.2%) of 2,050 eyes with fundus fluorescein angiography records. Among 195 cases in which all retinal arteries were demonstrated satisfactorily, the cilioretinal arteries were 1-6 in number, supplying 1-4 quadrants of the fundus, while in 102 cases (52.3%) they did not supply the macular area as conventionally believed. Besides, in another group of 129 eyes in which cilioretinal arteries were recognized with the ophthalmoscope, those in 28 eyes (21.7%) were disproved by angiography. Therefore, angiography should be the only means to confirm clinically diagnosed cilioretinal arteries. PMID- 1935449 TI - [The long-term effect of Nd:YAG laser iridotomy]. AB - The IOP was controlled in 40 eyes (31 cases) of primary angle-closure glaucoma with Nd:YAG laser iridotomy. On follow-ups in 3 years, the differences in IOP, visual acuity, and the peripheral chamber depth from the preoperative values were very significant. The iridotomy hole closed spontaneously in 4 eyes. The success rates were 94% and 91% at 6 months and 2 years postoperative respectively, while it dropped to 82.4% at the end of third year. PMID- 1935450 TI - [Clinical analysis of orbital cavernous hemangiomas]. AB - CT and B-ultrasonography in combination with clinical manifestations facilitated the diagnosis and orientation of 40 cases of orbital cavernous hemangioma. The surgical approach depended on the size and location of the tumors as determined by axial and coronal CT, and mostly adopted was the route of lateral orbitotomy. The prevention of complications was discussed. PMID- 1935451 TI - [Clinical and histopathological analysis of ocular lymphocytic inflammatory pseudotumors]. AB - 44 cases (56 eyes of 29 males and 15 females) of lymphocytic inflammatory pseudotumor were analysed. The average age of onset was 40.6 years. The chief manifestations consisted of orbital mass, proptosis, edema of the eyelids and bulbar conjunctiva, and limited eyeball motility. ESR was accelerated in 11 of 13 patients tested. Seral antibody of EB virus was positive in 2 of 3 patients examined. Immunohistochemically, all 3 patients examined showed polyclonality. A diffuse lymphocytic infiltration with other inflammatory cells and fibrovascular proliferation was the basic pathological picture. Histopathologically, the disease was classified into the diffuse infiltrative, fibrotic, and mixed types. The pathogenesis, the significance of immunohistochemical examinations, and treatment were discussed. PMID- 1935452 TI - [An immunological study of endogenous uveitis: circulating immune complexes and their specific characteristics]. AB - The levels of circulating immune complexes (CIC) in 77 patients with endogenous uveitis (EU) were found significantly higher than in healthy controls, and also closely correlated with activity of the disease. The CIC level declined during remission and became essentially normal when the disease recovered. CIC was positive in 20 (37.7%) of the 77 cases, and the positive rate was the highest (58.6%) in patients with acute EU. Retinal soluble antigen was found in CIC of 9 patients. The serum C3 level was in negative correlation with the CIC level, and restored to normal on recovery of the disease. The findings indicated that CIC played an important role in the pathogenesis of EU. PMID- 1935453 TI - Microscope-based multiparameter laser scanning cytometer yielding data comparable to flow cytometry data. AB - We describe a computer-controlled 10 microns spot size laser scanning cytometer for making multiple wavelength fluorescence and scatter measurements of unconstrained cells on a surface such as a microscope slide. Designated areas of slides placed on a microscope stage are automatically scanned, and cells which generate above-threshold scatter or fluorescence values are found and individually processed to determine a list of measurement parameters. For each fluorescence or scatter measurement parameter, this list contains the integrated and peak values and bit pattern images of a scan window centered on the cell. The measurement time, the position of the cell on the slide, and two segmentation indices are also included in the list. Measurement time, cell position, and properties derived from the bit patterns are used interchangeably with integrated or peak measurement values as coordinates of multiproperty displays. Cells may be selected for counting, data display in various forms, or visual observation based on their meeting complex criteria among a chain of two property screens. Cells with selected properties may be viewed during an experiment or retrospectively. A designated specimen field may be repeatedly remeasured to perform kinetic cell studies. An argon ion and a HeNe- based laser instrument have been constructed and software has been written and evaluated with the specific goal of increasing the precision of propidium iodide-stained cellular DNA measurements. Some of the capabilities of the instrument and its current performance are described. PMID- 1935454 TI - Digital morphonuclear analyses of sensitive versus resistant neoplastic cells to vinca-alkaloid, alkylating, and intercalating drugs. AB - We tested 12 resistant cell lines in vitro in order to evaluate common morphonuclear characteristics induced by various cytotoxic drugs on cell lines of different origins. We used the MXT mouse mammary cancer and the neoplastic J82 and T24 human bladder cell lines, whose variants are either sensitive or resistant to a vinca alkaloid derivative (Navelbine, NVB), to an investigational alkylating agent (PE1001), and to Adriamycin (ADR). We tested cell population variants resistant to NVB + PE1001 + ADR. The level of chemoresistance was evaluated by a colorimetric assay assessing the 50% concentration-induced inhibition of cellular growth (IC50) brought about by each drug on the growth of each cell variant under study. We show that resistant neoplastic cell nuclei present common morphonuclear characteristics, independent of cell origin (neoplastic mouse mammary versus human bladder cells) and the drug used (vinca alkaloid, alkylating, and intercalating derivatives). Our results further indicate that the phenotype of resistant versus sensitive cells corresponds to cell nuclei populations with smaller nuclei and less nuclear DNA content and, as a consequence, a chromatin texture showing large pale areas with some hyperchromatic clumps. PMID- 1935455 TI - Coincidence in high-speed flow cytometry: models and measurements. AB - In flow cytometry, the coincident arrival of particles becomes a major problem when high sample rates are required. For the development of our high-speed photodamage flow cytometer (ZAPPER), it was of importance to understand the behavior of cells at flow rates of around 50,000-250,000 event/s. We developed and compared two models that describe the relation between the real cell rate and the detectable single cell rate. Both the Computer Simulation model and the Input/Output Device model show distinct optima for the cell rate. The models were compared to measurements performed on the ZAPPER-prototype. Fits of the two models to the experimental data were excellent for cycle times of 4 and 15 microseconds and acceptable for a 2 microseconds cycle time. A third model (Mercer WB, Rev. Sci. Instr. 37:1515-1521,1966) could be fitted to the experimental data, after the proportionality constant k was adapted to the experimental data. At a yield of detectable single cells of 70%, the maximum cell rates are 180,000, 100,000, and 40,000 cells/s for cycle times of 2, 4, and 15 microseconds, respectively. Based on these results we can now select an optimal cell rate for analysis and sorting based on criteria such as accepted cell loss. In addition, the advantages of reducing the cycle time can now be evaluated with respect to the costs of that modification. PMID- 1935456 TI - Precision of DNA flow cytometry in inter-institutional analyses. AB - A Bladder Cancer Flow Cytometry Network study has been carried out to further identify and quantify sources of inter- and intra-laboratory variability. Replicate samples containing four mixtures of peripheral blood lymphocytes and aneuploid cell lines were distributed together with reference standards to six laboratories. The samples were stained for DNA using propidium iodide, with each laboratory using its own staining protocol. Two of each of the four sample types and a reference standard were analyzed by each laboratory on 3 separate days to obtain cellular DNA distributions. DNA index (DI) and hyperdiploid fraction (HDF) were calculated for each histogram using an automated technique. The results showed significant inter- and intra-laboratory differences. Results were evaluated by a two-way analysis of variance to estimate components of the overall variation attributable to individual sources. Error variation was found to be the major component of random variation. Specimen means were also compared for each laboratory. No significant differences were noted in mean DI for similar specimens; however, agreement in HDF between similar specimens was lacking in most laboratories. Prediction intervals were computed to estimate the range of values expected for a single specimen based on the analysis of the previous six. Prediction intervals for DI were quite good while those for HDF were troublesome due to wide variation. The results of these studies indicate that intra- and inter-laboratory variability are high enough that results for a single sample may not be sufficiently precise to allow comparison to results obtained in other laboratories.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1935457 TI - Improved prognostic impact of S-phase values from paraffin-embedded breast and prostate carcinomas after correcting for nuclear slicing. AB - Nuclear debris may significantly interfere with the analysis of S-phase fraction (SPF) from paraffin-embedded tumors. We used a background subtraction algorithm to compensate for the effects of slicing of tumor cell nuclei during preparation of paraffin-embedded specimens. DNA histograms were analyzed from 88 node negative breast and from 78 prostatic carcinomas. Median SPFs corrected for nuclear slicing were lower than uncorrected ones in both breast cancer (7.6% vs. 5.7%) and prostate cancer (6.7% vs. 4.2%). The median SPF value in each group was used as a cut-off point in survival studies. As compared with the uncorrected SPFs, corrected SPF levels resulted in a more significant survival difference between breast cancer patients with above and below median SPF (p = 0.0014 vs. p = 0.014) and in a higher relative risk (RR) of death (4.5 vs. 3.1). The same was true for prostate cancer survival (p less than 0.0001 vs. p = 0.002) and RR (5.3 vs. 3.1). Compared with the exponential background subtraction method, the sliced nuclei correction was more reproducible and could be applied in all evaluable histograms without the risk of overcompensation. In conclusion, our results support the use of background correction with the sliced nuclei model in DNA flow cytometric studies of archival tissues. PMID- 1935458 TI - Flow cytometric measurement of p53 protein expression and DNA content in paraffin embedded tissue from bronchial carcinomas. AB - The nuclear protein p53 has been measured in archival lung cancer biopsies. The monoclonal antibody PAb 1801, which recognizes human p53, was used. After immunostaining, the nuclei prepared from paraffin-embedded tissue were stained with propidium iodide for simultaneous measurement of DNA content; 17 of 24 lung cancers were p53 positive. The S-phase fraction in positive tumors was 22.9 +/- 6.4%, as compared to 13.6 +/- 6.1% in negative tumors (P less than 0.02). In ten of the positive tumors (two small cell carcinomas and eight non-small cell carcinomas), the p53 expression varied through cell cycle, whereas in seven tumors (five small cell carcinomas and two non-small cell carcinomas), no such variation of p53 expression was observed. Freezing the nuclear suspensions did not substantially reduce the p53 signals. Control experiments with the SV40 transformed human foreskin fibroblast cell line HSF4-T12 showed that the enzymatic digestion utilized to dissociate paraffin-embedded tissue did not significantly reduce p53 fluorescence. Immunohistochemical staining of biopsy specimens indicated that only cancer cells were overexpressing p53. In conclusion, using the monoclonal antibody PAb 1801, p53 is detectable in cell nuclei prepared from paraffin-embedded bronchial carcinoma biopsies. P53 positive tumors have increased proliferative activity compared to p53 negative tumors. Furthermore, the lack of cell cycle variation of p53 in small cell carcinomas indicates that this pattern may be related to high-grade malignancy. PMID- 1935460 TI - Very early detection of changes associated with cellular activation using a modified flow cytometer. AB - A sample station modification previously described has been redesigned to provide greater flexibility and enhanced performance. The improved modification provides mixing and temperature regulation in a compact unit that mounts close to the nozzle holder for reduced transit times, allowing for addition of mediators to a sample in place on the flow cytometer, with observation of results in approximately 1 s. An electronic circuit activated at the time of injection generates full-scale pulses in the forward scatter channel. This provides the data with a time stamp for direct correlation of injection and cellular response. A detailed description of the modification, performance verification data, and practical applications in the measurements associated with cellular activation are presented. PMID- 1935459 TI - Ki-67 labeling in postmitotic cells defines different Ki-67 pathways within the 2c compartment. AB - Simultaneous quantification of DNA and Ki-67 proliferation-associated antigen was performed using fluorescence image cytometry. In the MCF-7 cell line, the Ki-67 antigen content increases during the cell cycle, and its intranuclear distribution pattern varies. Quantitative evolution of Ki-67 content as a function of nuclear area makes it possible to define several pathways followed by cells going through the 2c compartment. 1) In some cells, the amount of Ki-67 antigen remains constant during G1 (Ki-67 stable pathway), and a characteristic speckled pattern can be observed. 2) In the larger fraction of cells analyzed, there is a postmitotic decrease in the Ki-67 (Ki-67 decrease pathway) content. In this pathway, labeling is located in the nucleoplasm in small nuclei, is located in nucleoli in intermediate-sized nuclei, and is absent from larger nuclei (G0). A progressive increase in Ki-67 content (Ki-67 increase pathway) was observed from intermediate-sized nuclei to S phase nuclei. From these results, we hypothesize that the Ki-67 stable pathway is the G1 phase of newly formed cells going directly to S phase in local optimal conditions of growth and that Ki-67 decrease pathway and Ki-67 increase pathway correspond to cells whose progression to S phase is regulated by extracellular factors. PMID- 1935461 TI - Simple delay monitor for droplet sorters. AB - We have constructed a simple device by which the optimal delay time between optical measurement of a cell and the application of the droplet charging pulse can be determined directly in a flow sorter. The device consists of a stainless steel chamber in which the sorted droplets are collected. In the collection chamber the collected droplets run through a capillary where a continuous fluorescence measurement is made. With a sample of fluorescent particles, the delay time is optimal when the measured fluorescence is maximal. The measuring volume is always filled with the last droplets sorted (about 3,000). With this device, the setting of the delay time can be done in a few seconds without the need for microscopical verification. The fluorescence in the collection chamber is excited and detected via optical fibers using about 10% of the light of the existing laser from the flow cytometer and an extra photomultiplier. PMID- 1935462 TI - Clinical applications of cytometry: 5th annual meeting. AB - The 5th annual Clinical Applications of Cytometry meeting was held September 12 15, 1990 in charleston, SC. The theme which emerged repeatedly throughout the meeting was the need to take full advantage of the quantitative power of cytometry to provide the most useful clinically relevant diagnostic and prognostic information. Greater quantitative power is based on careful and reproducible standards and quality control. The same principles, albeit with somewhat different approaches, apply to cell surface immunofluorescence analysis, DNA measurements, and image cytometry assessments. Monoclonal antibody probes against oncogenes, others against lymphokines within the Golgi, and a novel fluorogenic substrate designed to quantitate the activity of a mitochondrial enzyme were exciting developments described at the meeting. PMID- 1935463 TI - Subtotal colectomy for ulcerative colitis: complications related to the rectal remnant. AB - Complications related to the retained rectal remnant were reviewed in 136 patients undergoing subtotal colectomy for acute ulcerative colitis. Fifty-five patients (Group 1) had a closed rectal stump brought up into the subcutaneous tissue, and 30 (Group 2) had an open mucous fistula. These were compared with an intrapelvic Hartmann's pouch performed in 51 patients (Group 3). All patients eventually had a pelvic pouch procedure. Age, duration and activity of disease, and preoperative steroid use were similar in all groups. There was no mortality. The rectal stump in 19 Group 1 patients (35 percent) spontaneously opened, and seven (13 percent) developed local left lower quadrant wound infections. Two Group 1 patients (4 percent) developed pelvic septic complications, as compared with two Group 2 patients (7 percent) and six Group 3 patients (12 percent). Subsequent pelvic dissection was difficult in 20 percent of Group 3 patients, vs. 4 percent and 0 percent of Group 1 and Group 2 patients, respectively (P less than 0.05). Persistent rectal disease activity was present in 41 percent of Group 3, vs. 27 percent of Groups 1 and 2. Our study suggests that exteriorization of the closed rectal stump following subtotal colectomy is associated with fewer pelvic septic complications and minimal local morbidity, facilitates subsequent pelvic dissection, and is not associated with increased disease activity in the retained rectum. PMID- 1935464 TI - How reliable is measurement of the anorectal angle by videoproctography? AB - The anorectal angle can be determined either by constructing a straight line along the lower border of the rectum (Method A) or by using the central longitudinal axis of the lower rectum (Method B). We have used a computer program to derive the centroid of the rectum for Method B. The coefficients of variation for angles measured at rest, during maximum pelvic floor contraction, and during attempted defecation were 0.616, 0.351, and 0.358, respectively, compared with 0.993, 0.972, and 0.968 for Method B. The presence of a rectocele had no influence on the measurement of the anorectal angle in incontinence, but there was a significant difference in assessment of the angle between constipated patients (P less than 0.05) and controls (P less than 0.05). Posterior indentation of the rectum had no significant influence on measurement of the angle in any group. These data indicate that a computer-derived centroid is more reliable for measurement of angles, but a correction factor for anterior rectocele is needed in constipated patients and controls. PMID- 1935465 TI - Securing the loop--historic review of the methods used for creating a loop colostomy. AB - Loop transverse colostomy is a procedure that has been traditionally employed on a temporary basis for a number of indications, but, with improvement of intestinal suturing and stapling techniques, the applicability of this modality has become quite limited. This paper addresses the issue of securing the loop and traces the history of the development of this method to decompress the bowel, to divert the fecal stream, and to defunctionalize the distal colon. PMID- 1935466 TI - Primary epithelial apposition in colostomy. 1951. PMID- 1935467 TI - Primary syphilis of the rectum--endoscopic and clinical features. Report of a case. AB - A 33-year-old man was admitted to our hospital for suspected rectal tumor. Endoscopy showed a rectal mass not typical of carcinoma, and histologic evaluation of biopsy specimens revealed granulomatous inflammation. Venereal Disease Research Laboratories (VDRL) and Treponema pallidum hemagglutination (TPHA) tests became positive during hospitalization, and dark-field examination was positive for Treponemas, thus allowing the diagnosis of chancre of the rectum. The clinical and endoscopic features of this case are described. PMID- 1935468 TI - Sleeve advancement anorectoplasty for complicated anorectal/vaginal fistula. AB - Transanal flap-advancement procedures for complicated anorectal or rectovaginal fistula may include vertically incised flaps, horizontal flaps, and tubal flaps. Anatomic and pathologic considerations affecting choice of the three major techniques are examined in the context of their historical development over the last century. Application of the tubal (or sleeve) advancement principle is described in a woman whose combined rectovaginal and cryptogenic fistulas encompassed more than one-third of her anal circumference, necessitating surgical modifications beyond those afforded by previously documented techniques. Obliteration of disease and preservation of sphincteric competence were the achieved objectives of the procedure. Rationale for the procedure and technical details of the sleeve advancement anorectoplasty are described, mindful of the surgical antecedents of this therapeutic option. PMID- 1935469 TI - Avoiding colostomy soiling during immediate maturation after Hartmann's procedure. AB - A simple maneuver that avoids soiling of the field during immediate maturation of colostomy performed for large bowel obstruction is presented. This maneuver involves inflating a large Foley catheter in the lumen of the obstructed large bowel just before maturation is performed. PMID- 1935470 TI - Inverted U-pouch construction for restoration of function in patients with failed straight ileoanal pull-throughs. AB - Patients who have undergone straight ileoanal pull-through operations without a reservoir in adult life frequently have unsatisfactory results. Operative correction of this problem has been difficult. We propose a new operation that preserves the ileoanal anastomosis, constructs a reservoir, and has resulted in good restoration of bowel function in three patients. The operative procedure consists of division of the ileum 30 cm above the dentate line. The distal ileum is then folded over itself so that the point of division reaches into the pelvis, between the rectal muscular cuff and pulled-through ileum, to a point just proximal to the dentate line. The two limbs of ileum are connected using a stapler, completing the reservoir construction. The proximal divided ileum is anastomosed, end-to-side, to the pouch. A protective ileostomy that can be closed in three months is constructed. PMID- 1935471 TI - Colovaginal fistula secondary to diverticular disease. AB - Colovaginal fistula is infrequently encountered in gynecologic practice, but, when it does occur, diverticular disease is the most common cause. This paper discusses current concepts in etiology, diagnosis, and treatment of patients with colovaginal fistula secondary to diverticular disease. Review of the literature reveals that a majority of patients have a history of hysterectomy and are primarily diagnosed by barium enema. The current trend in treatment is surgical correction with primary resection and anastomosis. PMID- 1935472 TI - Anal canal carcinoma: a historical account. PMID- 1935473 TI - Abdominal colon and rectal operations in the elderly. AB - Sixty-seven abdominal operations for colon and rectal disorders were performed on 56 patients 80 years of age or older from January 1, 1984 to June 30, 1989. Nine patients required multiple operations. Sixty-two procedures (92 percent) were performed on patients in their ninth decade; two operations were performed on patients 95 years of age or older. Forty-five patients (80 percent) were operated upon for carcinoma. Operations included segmental colectomy (33 patients), low anterior resection (12 patients), total abdominal colectomy (3 patients) and abdominoperineal resection (2 patients). Forty patients were classified as ASA Class III; the majority were monitored in the surgical intensive care unit for a mean of 2.84 days. Thirty patients were monitored with arterial catheters and 21 with central invasive monitoring. Operative mortality was 7 percent (4 patients). Two patients died from diffuse carcinomatosis; one patient had a fatal myocardial infarction. The final death occurred from multisystem organ failure following anastomotic dehiscence. Twenty-seven operations were performed without postoperative complications; 18 operations were followed by a single minor complication. The average hospital stay was 18.96 days. All patients were admitted from home. Thirty-three returned home postoperatively; 16 were discharged to an extended care facility. In conclusion, elderly patients with colon and rectal disorders can be operated upon with acceptable morbidity and mortality. Age alone should not interdict surgical therapy. PMID- 1935474 TI - Rectocele in males: clinical, defecographic, and CT study of singular cases. AB - The authors report eight cases of rectocele in male subjects studied with defecography and computed tomography. The pocket is located between the prostatic apex and the urogenital diaphragm. The abnormality has clinical significance. PMID- 1935475 TI - Functional assessment of coloanal anastomosis with reservoir and excision of the anal transition zone. AB - Conservation of the anal transition zone (ATZ) has been deemed necessary for continence after coloanal anastomosis (CAA) with reservoir. Therefore, we have studied functional and manometric results after CAA with reservoir and excision of the ATZ in 18 consecutive patients (mean age, 65.2 years; ten males and eight females), 17.4 months after closure of a temporary loop colostomy (Study 1). Twelve of the 18 initial patients were studied again 30.2 months after closure (Study 2). In Study 1, all patients underwent 1) a standardized interview, 2) a manometric study with measurement of anal pressure at rest (PR), voluntary contraction (VC), inhibitor anal reflex (IAR), conscious sensation (CS), and maximum tolerable volume (MTV), and 3) a liquid continence test (LCT) with measurement of colonic reservoir pressure during infusion. In Study 2, patients underwent all the same tests except the LCT. Results were compared with those of six controls (mean age, 65.8 years; two females and four males). In Study 1, 14/18 patients were continent; PR, VC, and CS did not differ among continent patients, incontinent patients, and controls. MTV was significantly lower in incontinent patients (mean +/- SD, 165 +/- 46.5 ml) than in continent patients and controls (mean +/- SD, 261 +/- 50.8 ml vs. 250.7 +/- 83 ml). IAR was not observed in continent or incontinent patients but was observed in controls. Contraction waves in the colonic reservoir during LCT were more frequent in incontinent patients (4/4) than in continent patients (4/14), and their amplitudes were higher (119 vs. 32 mm Hg). In Study 2, 12/12 patients were continent; PR and MTV remained unchanged except in the two initially incontinent patients, in whom MTV was increased. VC was slightly increased (94.7 vs. 116 mm Hg). IAR remained absent in all patients. We conclude that 1) excision of the ATZ did not increase the risk of incontinence, and 2) poor functional results were mainly due to small MTV and contraction waves in the colonic reservoir. PMID- 1935476 TI - Percutaneous decompression and irrigation for large bowel obstruction. New approach. AB - This investigation introduces percutaneous decompression and irrigation of the obstructed large bowel as a simple and safe procedure that can be undertaken for the emergency situation. This procedure was performed in 28 patients who presented with colonic obstruction caused by sigmoidal or rectosigmoidal carcinoma without any complications. It allowed patients to be properly prepared and investigated and then to receive definitive colonic surgery 36-48 hours after the decompression. Therefore, it is concluded that percutaneous decompression and irrigation can on one hand defer emergency surgery for colonic obstruction and on the other hand enable a one-stage definitive procedure to be undertaken during the same admission. PMID- 1935477 TI - Clinicopathologic features of the flat adenoma. AB - One hundred twenty-eight small flat adenomas (SFAs) were collected from 101 patients, and the clinicopathologic features were investigated. There were 91 adenomas with mild atypia, 20 with moderate atypia, and 17 with severe atypia. SFAs were found more often in males than in females, with a ratio of 3.4:1, and the malignancy rate in females (31.8 percent) was higher than in males (9.3 percent). About 38 percent of the patients had a history of colorectal carcinoma, and 65 percent had a history of colorectal neoplasms. Of 37 patients whose family history was traced, 21 had cancer families. SFAs were prone to be found in patients with a history of colorectal neoplasms and a cancer family. Malignancy rate increased with increasing size. The overall malignancy rate was 13.3 percent, which was considerably higher than that of ordinary small polypoid adenomas (2.8 percent). SFAs were situated more proximally (30.9 percent) than ordinary adenomas; however, there was no relationship between site and malignancy. All the lesions showed tubular adenomas, and there was no villous feature. A central depression was noted in 20 lesions, more frequently in adenomas with higher atypia. All but one adenoma with severe atypia showed a component of lower atypia, supporting the adenoma-carcinoma sequence. PMID- 1935480 TI - Oral cancer detection and the dentist's responsibility. PMID- 1935479 TI - Recognition of the eating disorder patient. PMID- 1935478 TI - Rodless end-loop stomas. Seven-year experience. AB - The rodless, end-loop stoma was developed as an alternative to the more traditional loop stoma to minimize patient management problems. A retrospective review of our seven-year experience in 229 patients with end-loop colostomies (135), ileocolostomies (70), and ileostomies (24) is presented. A total of 30 stoma-related complications were observed in 27 stomas, for an overall complication rate of 13.1 percent. The most common complications were skin excoriation secondary to leakage (3.5 percent), retraction (3.5 percent), partial necrosis (2.6 percent), and peristomal sepsis (1.8 percent). Mucocutaneous separation, prolapse, and stenosis were each seen in less than one percent of patients. No cases of stomal herniation, obstruction, or hemorrhage were encountered. Twelve deaths occurred, but none was attributed to stoma-related complications. The rodless, end-loop stoma is a simple and safe procedure with many advantages and a low incidence of complications. PMID- 1935481 TI - What in the world was the matter with John Merrick? Neurofibromatosis: a review of the disease. PMID- 1935482 TI - Mouthguard use should be encouraged for many sports. PMID- 1935483 TI - Detection of child abuse. PMID- 1935484 TI - Walking the tightrope: balancing profit motives and patient service. PMID- 1935485 TI - Dentistry: a profession to smile about. PMID- 1935486 TI - The ins and outs of staff selection. PMID- 1935487 TI - How to hire a winning dental staff. PMID- 1935488 TI - Referral of patients for orthodontic treatment. PMID- 1935489 TI - Starting a dental practice from scratch. PMID- 1935490 TI - Saving money through inventory control. PMID- 1935491 TI - A new method for measurement of blood flow, pH, and transmucosal potential difference in rat gastroduodenal mucosa by endoscopy. AB - A method was developed to measure the mucosal blood flow (BF), mucosal pH (pH), and transmucosal potential difference (PD) in various sites from the oral cavity to the duodenum without surgical operation or damage to the subject rats. These measurements were carried out by using three indicator electrodes, which were attached to the various sites through the suction channel of an endoscope. The hydrogen gas clearance method was used for the measurement of BF. BF values obtained at the fundic, pyloric, and duodenal regions were 119 +/- 17, 69.9 +/- 8.8, and 114 +/- 18 ml/min/100 g (mean +/- SE), respectively. The pH values were lowest at the cardiac portion and the forestomach and highest at the duodenum. PD showed higher values at the stomach and lower values at the pharynx and duodenum. Using this technique, it was possible to measure the BF, pH, and PD repeatedly and safely at various sites in the same rat. Therefore, it was suggested that this method is useful in studying the physiological functions of the stomach and duodenum and the pathogenesis of gastroduodenal ulceration and that this method is applicable to measure the change of the above parameters in the healing process of gastric ulcer in rats. PMID- 1935492 TI - Circadian rhythms of gastric mucus efflux and residual mucus gel in the fasting rat stomach. AB - We hypothesized that two putative gastric protective factors, mucus efflux and residual mucus gel content, would manifest circadian rhythms, as reported in several other gastric functions. Rats were adapted for three weeks on a 12-hr light schedule, fasted 18-hr and studied at 3-hr intervals. Under anesthesia, the stomachs were cannulated and filled with test solution. Thirty minutes later, they were drained and the luminal fluid was analyzed for mucus content by Alcian blue binding. Residual mucus gel was determined by direct injection of dye into the lumen. Alcian blue binding of rat mucus was expressed as equivalent milligrams of porcine mucin. Both parameters showed a significant (P less than 0.001) circadian rhythm. Mucus efflux peaked at 5:03 +/- 0:52 HALO (hours after lights on), and residual mucus at 6:00 +/- 0.46 HALO. Thus, the interplay of circadian rhythms in aggressive and defensive gastric mucosal functions is supported. PMID- 1935493 TI - Completion gastrectomy for refractory gastroparesis following surgery for peptic ulcer disease. Long-term follow-up with subjective and objective parameters. AB - We recently have shown that 50% of patients with preoperative gastric outlet obstruction go on to develop chronic nonmechanical gastric stasis after surgery and require further operations in attempts to relieve their symptoms. In the present study we report our experience with completion gastrectomy (CG), offered to a subgroup of this population who failed to respond to both available and experimental medical therapy with prokinetic agents. Manometric studies of the small bowel were performed on three of these patients using a semiconductor solid recording probe to assess the motility of efferent jejunal limbs. There were seven females and one male (N = 8) with a mean age of 45 years. All had persistent symptoms of abdominal pain, bloating, nausea, vomiting, early satiety, decreased appetite, and weight loss dating back to the time of surgery. Gastric stasis was documented by delayed gastric emptying of a radionuclide solid meal (chicken liver labeled with technetium-99m sulfur colloid) with a mean retention of 86 +/- 6.2% (less than 60% being normal) in the setting of an upper endoscopy showing stomal patency. The mean duration of symptoms was 31.6 +/- 15.7 months (range 6-60) since the last surgery. The number of previous gastric operations was a mean of 2.3 per patient. Five of eight patients had undergone a Roux-en-Y procedure as the last operation while the other three had a Billroth II. Surgery consisted of a 90% or complete resection of the remaining stomach and a jejunal esophageal anastomosis. In some cases the Roux-en-Y limb was lengthened to greater than 45 cm if needed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1935494 TI - Misoprostol but not antacid prevents endotoxin-induced gastric mucosal injury: role of tumor necrosis factor-alpha. AB - Many of the complications of septic shock are believed to be a consequence of elevated circulating levels of tumor necrosis factor (TNF), which is an important mediator of tissue injury. Prostaglandins (PGs) of the E series have recently been reported to inhibit TNF production in vitro. We investigated the in vivo effect of misoprostol, a PGE1 analog, on endotoxin-induced gastric mucosal injury and TNF production. For the gastric mucosal injury studies, groups of animals were pretreated with intragastric misoprostol (100 and 200 micrograms/kg) or with antacid (2 ml/animal of Maalox Plus) 30 min prior to a challenge with intravenous E. coli lipopolysaccharide (LPS) at 5.0 mg/kg. Stomachs were examined 3 hr after LPS. Systemic endotoxin alone induced microscopic edema, vascular congestion, and polymorphonuclear (PMN) infiltration of the gastric mucosa. Pretreatment with misoprostol, but not with antacid, significantly and dose-dependently reduced the gastric mucosal injury. For the TNF studies, groups of rats were given either misoprostol (100 or 200 micrograms/kg, intragastric), or saline 1 hr prior to LPS challenge. Serum samples were obtained 1.5 hr after LPS challenge. Misoprostol dose-dependently and significantly (P less than 0.01) inhibited TNF activity. We conclude that misoprostol is a potent inhibitor of TNF systemic production and inhibits the gastric mucosal injury induced by endotoxemia. These studies suggest a potentially important therapeutic role for misoprostol in inflammatory diseases in which TNF exerts a contributory role. PMID- 1935495 TI - 6-Mercaptopurine and spermatogenesis in the young rat. AB - In recent years, 6-MP treatment has been beneficial in the treatment of inflammatory bowel disease (IBD). Since 6-MP and its metabolites interfere with various steps in nucleic acid biosynthesis, chronic use of 6-MP could theoretically alter normal cell turnover, including spermatogenesis. Therefore, we have investigated the effect of daily 6-MP administration on spermatogenesis in the young rat. 6-Mercaptopurine was administered in clinically relevant doses 24 and 40 mg/m2. Testicular weights of rats treated with 24 mg/m2 for 75 days or 40 mg/m2 for 25 days were not significantly different among 6-MP, pair-fed, or ad libitum chow-fed groups. Quantitation of the stages of seminiferous tubules or the number of homogenization-resistant, mature spermatids per testis were not affected by 6-MP treatment. In addition, 6-MP had no effect on serum testosterone or on HCG-stimulated testosterone release by the testes. These results suggest that chronic low-dose 6-MP therapy, as used in the treatment of IBD, may not carry as great a risk for suppression of spermatogenesis as theorized. Our study in animals indicates that evaluation of 6-MP and spermatogenesis in man is warranted. PMID- 1935496 TI - Factors affecting plasma postheparin diamine oxidase activity. AB - Plasma postheparin diamine oxidase (DAO) activity has been evaluated for assessing disease activity in Crohn's disease (CD) and other intestinal disorders. Since the mechanism of the reduced plasma DAO activity is poorly understood, our aim was to determine the effect of extent and location of disease and prior resection and therapy on plasma DAO activity in Crohn's disease. Plasma postheparin DAO activity was significantly lower (17.4 +/- 3.0 vs 32.8 +/- 30.8 units/ml) and Crohn's disease activity index (178 +/- 105 vs 14 +/- 19, P less than 0.05) (CDAI) higher in 37 patients with CD compared to 30 normal volunteers. There was no overall correlation between DAO activity and CDAI. Effective medical or surgical therapy increased DAO activity and decreased CDAI, while clinical recurrence had the opposite effect. DAO activity was not related to the extent of small bowel disease (13.2 +/- 9.1; less than 30 cm, 18.5 +/- 11.8; 30-60 cm, and 5.7 +/- 6.4 units/ml; greater than 60 cm) or colonic disease (13.0 +/- 6.9 segmental vs 24.0 +/- 15.4 units/ml, pancolitis). DAO activity was similar with small or large bowel disease (14.3 +/- 10.6 vs 18.8 +/- 13.1 units/ml). Prior enterectomy or colectomy did not significantly influence DAO activity. DAO activity responds predictably after effective therapy and recurrence and may prove useful in monitoring individual patients with CD. Failure of extent and location of disease and prior resection to influence DAO activity suggests that DAO activity is not directly related to enterocyte mass. PMID- 1935497 TI - Creatine kinase isoenzymes in the diagnosis of intestinal infarction. AB - Total creatine kinase and its isoenzymes CK-MB and CK-BB were measured in the serum of patients admitted with acute abdominal pain or signs suggestive of an intraabdominal catastrophe. Total creatine kinase was measured by automated spectrophotometry, CK-MB by chemiluminescent assay, and CK-BB by radioimmunoassay. Patients were grouped according to their final diagnosis: intestinal infarction (N = 8); all other diagnoses (N = 22); controls (N = 20). CK-BB in the infarction group (22.3 +/- 5.3 ng/ml, mean +/- SE) was significantly greater (P less than 0.01) than in the noninfarction or the control groups (11.0 +/- 0.8 ng/ml and 5.8 +/- 0.7 ng/ml, respectively). There were no differences in total creatine kinase and CK-MB in the three groups. Stepwise deletion multiple regression analysis of 26 independent regressors showed that among a cluster of six significant variables (R2 = 0.92, P less than 0.005), CK-BB greater than 20 ng/ml was the best predictor of intestinal infarction. Results of this study indicate that CK-BB isoenzyme measurement may be useful in the diagnosis of intestinal infarction in man. PMID- 1935498 TI - Response of canine ileocolonic sphincter to intraluminal acetic acid and colonic distension. AB - The aim was to determine the effect of intraluminal acetic acid and proximal colonic distension on canine ileocolonic sphincter pressure, ileal motility, and coloileal reflux. In six conscious dogs with an isolated ileocolonic loop, basal pressure of the ileocolonic sphincter was similar during ileal perfusion with 100 mM acetic acid at 1 ml/min (mean +/- SEM = 18 +/- 0.4 mm Hg) and with saline (18 +/- 0.5 mm Hg; P = 0.81). Discrete clustered ileal contractions were more frequent with acetic acid, however, and when they propagated across the sphincter, sphincter pressure increased from 18 +/- 0.4 mm Hg to 36 +/- 1.3 mm Hg (P = 0.002). Sphincter pressure was also greater during colonic perfusion with acetic acid (32 +/- 0.7 mm Hg) than during ileal perfusion with acetic acid or saline (P less than 0.017). Moreover, sphincter pressure gradually increased as the colon was distended with saline (slope = 0.8 mm Hg/cm H2O, P less than 0.017) or acetic acid (slope = 0.5 mm Hg/cm H2O, P less than 0.017), but the increase did not prevent coloileal reflux. In conclusion, ileal clustered contractions, colonic perfusion of acetic acid, and colonic distension all increased canine ileocolonic sphincter pressure. PMID- 1935499 TI - Colonic fermentation of potato starch after a freeze-thaw cycle. AB - To estimate colonic carbohydrate fermentation following a potato meal, 13 healthy volunteers consumed 375 g potatoes containing 60 g starch on three different occasions in random order: (A) potatoes boiled and consumed fresh at 60 degrees C; (B) potatoes boiled, frozen, thawed and consumed at 20 degrees C; and (C) potatoes boiled, frozen, thawed, reheated to 90 degrees C, and consumed at 60 degrees C. End-expiratory breath hydrogen (H2) was measured every 15 min for 10 14 hr with a selective electrochemical cell. The extent of colonic carbohydrate fermentation (AUC = area under the breath H2 concentration vs time curve) in experiment B was significantly higher (+186%, P less than 0.002) than in experiment A. The breath hydrogen AUC in experiment C was higher than in experiment A (+48%, P less than 0.04) but lower than in experiment B (-94%, P less than 0.003). It is suggested that structural alterations of the starch molecule occur during freezing, thawing, and reheating and alter the availability of carbohydrates for fermentation by colonic anaerobes. PMID- 1935500 TI - Different mechanism of magnesium and calcium transport across rat duodenum. AB - Concentration and voltage dependence of Mg transport across the rat duodenum was measured in an Ussing chamber. Mucosa (m) to serosa (s) Mg flux exhibits a cellular fraction comparable to that found for Ca. Mg sm flux is purely diffusive and probably restricted to the paracellular pathway. At all concentrations between 0.5 and 5 mmol/liter, Mg is secreted. Diffuse sm Mg flux is 3.5 times higher than the diffusive component of ms Mg transport. This prevalence of diffusive sm Mg flux over that from mucosa to serosa, which may be explained by an "anomalous solvent drag effect," is responsible for the Mg secretion observed. Mg 5 mmol/liter decreases ms Ca flux and abolishes Ca absorption. The voltage clamp experiments reveal that Mg has no effect on the cellular transport but only decreases diffusive ms Ca flux. 1 alpha,25-dihydroxyvitamin D3 has only a small effect on cellular Mg transport but remarkably stimulates ms Ca flux and increases Ca absorption by about 85%. Dexamethasone increases ms Mg flux but decreases ms Ca transport and hereby abolished Mg secretion or Ca absorption. In conclusion, Mg is secreted across the short-circuited duodenum whereas Ca is absorbed. There is evidence that both earth alkalines are transported by distinct cellular mechanisms. The data also demonstrate that diffusive movement across the paracellular pathway plays an important role on net Mg transport. PMID- 1935501 TI - Verapamil and furosemide prevent cholecystokinin-induced translocation of immunoglobulins in rat intestine. AB - Our previous studies have shown that cholecystokinin and pilocarpine are known to be extracellular messengers promoting the release of immunoglobulins A and G antibody activity in the lumen of the rat intestine. In the present study, which was also performed in rats, we show that CCK also promotes the translocation of albumin, electrolytes, and water into the lumen of the intestine. The effect of CCK on the translocation of immunoglobulins, albumin, and electrolytes is reduced by the prior injection of the calcium-channel blocker verapamil and the chloride channel blocker furosemide. Taken together, the above observations suggest that the translocation of immunoglobulins, albumin, and electrolytes in the intestine appears to be stimulated by identical mechanisms and to proceed simultaneously. PMID- 1935502 TI - Dissociation of cholecystokinin and pancreaticobiliary response to intraduodenal bile acids and cholestyramine in humans. AB - The role of intraduodenal bile acids in the regulation of cholecystokinin (CCK), pancreatic polypeptide (PP), and secretin as well as exocrine pancreatic and biliary secretion was investigated by means of a duodenal marker perfusion technique in volunteers. The following solutions were perfused: (1) liquid test meal, (2) test meal with 6 g cholestyramine, (3) test meal with 2 g chenodeoxycholic acid (CDC), (4) test meal with 6 g cholestyramine and 2 g CDC, (5) 6 g cholestyramine alone, and (6) 2 g CDC alone. The test meal caused an immediate increase in CCK and PP plasma levels, whereas secretin was not significantly altered. CCK release was further enhanced by addition of cholestyramine, whereas CDC inhibited release. The stimulatory effect of cholestyramine was abolished by CDC. CDC alone and in combination with the test meal stimulated secretin release. The response of PP to the test meal was not altered by addition of either compound. Cholestyramine and CDC alone caused only a very small increase in CCK levels, whereas PP was stimulated to nearly postprandial values. Meal-stimulated pancreatic and biliary secretion was significantly enhanced by cholestyramine, CDC, and the combination of both. CDC and cholestyramine alone each stimulated enzyme and bile secretion to a greater extent than the test meal. We conclude that intraduodenal bile salts are a modulator of postprandial CCK release. Changes in exocrine pancreatic and biliary and PP secretion do not necessarily parallel CCK concentrations, suggesting that different mediators are involved in the observed bile acid-induced changes in humans. PMID- 1935504 TI - Ischemic colitis of the cecum after renal transplantation masquerading as malignant disease. AB - Fourteen years after kidney transplantation and following protracted rejection of the transplant, a patient developed abdominal pain, fever, and leukocytosis. Ultrasound demonstrated a pericolic abscess, and barium enema a deformity of the ascending colon suggesting malignant growth. Colonoscopy showed ulcerative and necrotic lesions of the cecum, and colonic carcinoma was suspected. At surgery, a granulomatous inflammatory reaction with fibrosis involving the kidney transplant and cecum was found. Histological examination revealed ulcerations secondary to ischemic colitis, but no malignancy. Thus, ischemic colitis should be ruled out in cases with a presumptive diagnosis of colonic malignancy at x-ray or endoscopy. PMID- 1935503 TI - The amygdala. Emotions and gut functions. AB - Studies are reviewed that indicate that the amygdala, and its temporal lobe pathways connecting it with entorhinal cortex and hippocampus, modulates the effects of stressful conditions on the development of gastric pathology. The amygdala integrates aversive stimulus conditions with the defensive behaviors and visceral reactions seen under such circumstances. The transmitter mechanisms for these effects include dopamine, gamma-aminobutyric acid, thyrotropin-releasing hormone, neurotensin, enkephalins, and endorphins. Recording data also show that distinct neural "signatures" in this temporal lobe region correlate with the vulnerability to stressful experiences. The efficacy of synaptic transmission, as represented by potentiation or suppression of recorded neuronal responses, is an indication of coping adjustments, ie, habituation or behavioral helplessness. Glutamate receptors in this brain region, activated by N-methyl-D-aspartate, are implicated in these behavioral strategies. It is proposed that the neurophysiology of these limbic system structures produces individual differences in stress ulcer severity. PMID- 1935505 TI - Hemolysis, elevated liver enzymes, and low platelets in pregnancy (HELLP syndrome). A case report and literature review. PMID- 1935506 TI - Primary adenocarcinoma of duodenal bulb benefitted by chemotherapy. AB - A 48-year-old man had primary adenocarcinoma of the duodenal bulb. The extensive hepatic metastasis of the patient did not allow any major surgical procedure. Therefore UFTM chemotherapy was performed and was associated with three years of improvement. Subjective symptoms were relieved and test findings indicated normalization of liver biochemistry as well as CEA and CA 19-9. X-ray, endoscopy, and pathological findings indicated the disappearance of the carcinoma of the duodenal bulb. In addition, both ultrasonic examination and CT of the abdomen showed marked reduction of the hepatic metastasis. The authors do not hesitate to recommend the UFTM therapy as a therapeutic modality for inoperable and metastatic primary adenocarcinoma of the duodenum. PMID- 1935508 TI - Seeing, not just looking. PMID- 1935507 TI - Thyroid dysfunction and liver injury following alpha-interferon treatment of chronic viral hepatitis. PMID- 1935509 TI - Vaginocervical cytology in victims of sexual assault. AB - To investigate the role of vaginocervical smears in alleged victims of rape, we reviewed the findings in 4,220 consecutive rape victims between the years 1982 and 1989. These rape victims showed a slight increase in cellular abnormalities (1.18% vs. .93%) when compared to a group of 17,187 routine smears from an indigent population in 1989. While the differences in the spectrum of cellular abnormalities were not statistically significant, the increase in abnormal smears is remarkable because of the younger age distribution and lower risk factors for cervical cancer in this group of rape victims (41% of the victims were never seen at our institution before their evaluation for alleged rape and were most probably of higher socioeconomic status and at lower risk for cervical cancer than the indigent population served at our hospital). This finding may reflect the low incidence of vaginocervical cytology screening among the general population of which rape victims are a random sample. Fifty-seven percent of the rape victims with cellular abnormalities who were also regular patients at our hospital returned for follow-up by appropriate repeat smears or biopsies. This was lower than the 95% general follow-up rate of vaginocervical smear abnormalities among the rest of the population screened at our hospital. We detected spermatozoa in 56% of the smears from victims who were examined within three days of the alleged sexual assault. Cytology adds to the criminal investigation of rape cases as we detected spermatozoa in four of 16 semen negative cases from a random sample of 53 cases evaluated by the state crime lab. PMID- 1935510 TI - Pancreatic adenocarcinoma: regression analysis to identify improved cytologic criteria. AB - The incidence of pancreatic adenocarcinoma is increasing and it is usually unresectable at the time of diagnosis. Consequently, fine-needle aspiration biopsy (FNAB) is being used more frequently for diagnosis. The reported sensitivity of diagnosing pancreatic adenocarcinoma by FNAB has varied between 50% and 100%. In an attempt to increase the diagnostic sensitivity, we retrospectively reviewed a series of pancreatic FNABs. Fifteen cytologic criteria were evaluated in 78 patients who had pancreatic FNABs. Of these patients, 49 had primary adenocarcinomas and 29 had benign, non-neoplastic lesions. Using a stepwise logistic regression analysis we identified three key cytologic criteria for this diagnosis. Our study identified anisonucleosis (P = 0.001), large nuclei (P = .007), and nuclear molding (P = .03) as the significant cytologic features for diagnosing pancreatic adenocarcinoma. In combination, these three criteria had a sensitivity of 98% and a specificity of 100%. PMID- 1935511 TI - Cervical carcinogenesis and contraception. AB - Cytologic evaluation of cervical smears has been carried out in 3,374 women who used different modes of contraception (Lippes loop, copper T200, copper T220, copper devices containing higher copper content than the copper T200, CuT380 Ag, levonorgestrel IUD, injections of noresthisterone oenanthate, and subdermal implants of levonorgestrel) under the Contraceptive Testing Programme of Indian Council of Medical Research for periods ranging from 6 months to 15 yr. While no case of severe dysplasia or malignancy was noticed with any type of contraceptive, 113 dysplastic smears (99 mild and 14 moderate) were encountered on follow-up, giving an incidence of 3.3%, which was statistically insignificant compared with the pretreatment incidence of 1.4% (47 of 3,374). The highest incidence of dysplasia was seen with devices containing a high copper content (9.2%), followed by CuT200 (6.1%) and levonorgestrel implants (4.2%), and was lowest with Lippes loop (1.8%), injection of noresthisterone oenanthate (1.7%), and CuT380 Ag (1.5%), but statistics higher than the pretreatment incidence of 1.4% were seen only with CuT200 and devices containing high copper content. Retrogression of dysplasia was seen in 85 of the 94 posttreatment dysplasia cases and in all 47 pretreatment dysplasia cases, whereas in the remaining nine posttreatment cases of dysplasia the lesion persisted for 6-12 mo, necessitating discontinuation of contraception. The accumulated follow-up data indicate that the CuT380 Ag device is a promising IUD for the future in view of its low incidence of dysplasia determined during its use up to 5 yr. However, more prolonged follow-up in larger numbers of subjects is required to confirm its innocuousness on long-term retention. PMID- 1935513 TI - Changing utilization of cytopathology versus histopathology in the diagnosis of lung cancer. AB - We studied the utilization rates of 1) cytopathology procedures [sputum, fine needle aspirates (FNA), bronchial washings and brushings] versus 2) histopathology procedures (bronchial biopsies, lymph node biopsies, lobectomies, pneumonectomies) in the diagnosis of lung cancer, over two time periods (1967/1987). Comparisons were made in the utilization rates of these two diagnostic procedures in two groups of 100 patients each. Statistically significant changes included 1) an increase of cytopathology procedures, as the sole means of diagnosis; 2) an increase in FNAs; 3) an increased percentage of positive cytopathologic diagnosis; and 4) a decrease of major surgical procedures (lobectomy, pneumonectomy), as means of initial pathologic diagnosis. This study provides data supporting the trend of decreasing surgical procedures for initial diagnosis of lung cancer, with greater, more effective utilization of cytopathologic (particularly FNA) procedures. PMID- 1935512 TI - Pulmonary cytology in lung transplant recipients: recent trends in laboratory utilization. AB - The value of bronchoscopy for the diagnosis of rejection and opportunistic infection in lung transplant recipients is controversial. We review our experience with pulmonary cytology obtained from 10 lung transplant recipients during the first 15 mos of the transplantation program at Cedars-Sinai Medical Center and compare the efficacy of pulmonary cytology for the diagnosis of opportunistic infectious agents with that of histology and microbiology. Our study encompasses 1,465 post-transplant days during which 70 bronchoscopies were performed yielding 94 cytologic specimens (44 bronchial washes, 25 bronchial brushings, and 25 bronchoalveolar lavages) and 55 transbronchial biopsies. The major advantages of cytology in this setting are short turn around time and high specificity for nonbacterial agents. All of the patients experienced episodes of bacterial pneumonia as well as fungal and viral infections. None developed Pneumocystis carinii infection during the study period. Simultaneous and concurrent infections were diagnosed. The initial diagnosis of bacterial pneumonia and herpes simplex virus preceded the diagnosis of cytomegalovirus; the former infections tended to persist and/or recur. Cytology was more effective than histology in establishing the diagnosis of Candida sp. and herpes simplex virus, while histology was more effective in establishing the diagnosis of cytomegalovirus. Increased numbers of polymorphonuclear cells did not constitute a consistent finding in cytologic or histologic samples during episodes of bacterial infection; cultures were most sensitive for detection of bacterial infection. Histochemical and immunohistochemical stains as well as in situ hybridization studies confirmed diagnoses rendered on routine Papanicolaou and hematoxylin and eosin stained material but did not provide additional diagnoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1935514 TI - Needle aspiration cytology and immunocytochemical study in a case of angiosarcoma of the breast. AB - A case of angiosarcoma of breast diagnosed by needle aspiration cytology (NAC) is documented. The significant features which enabled the NAC diagnosis included presence of spindly to polygonal malignant endothelial lining cells appearing as papillary tufts merging with solid areas, branching effects, and presence of microacinar structures lined with abnormal spindly to polygonal cells indicative of vasoformative structures. Immunostaining for factor VIII and vimentin was strongly positive in the malignant spindly polygonal endothelial cells and further supported the NAC diagnosis. Similar findings were also seen in sections of cell blocks from aspirate and excised biopsy tissue from the breast tumor in hematoxylin-eosin stained sections and on immunostaining. Despite the rarity of occurrence of angiosarcoma in the breast it was felt that its cytologic diagnosis is possible especially in cases in which the lesion is extensive because of a good chance of getting a cellular sample on aspiration. This can be of considerable value for deciding an appropriate management and as a possible guide to prognosis. PMID- 1935515 TI - Cytodiagnosis of colonic adenoma: morphology and clinical importance. AB - This is a retrospective review of 74 colonic brushings with a view to identify colonic adenomas and recognize the cytologic features of villous adenoma (VA) and tubular adenoma (TA). Smears were reviewed for overall field pattern as well as individual cellular changes. The results were tabulated and analyzed for differences and similarities. The most distinguishing feature of adenoma was the presence of isolated and clustered elongate "needle" and "fan" cells as first described by Thabet. These were more abundant and in papillary cluster formations in VA as opposed to clusters of more blunted configuration in TA. Another striking feature of VA was an abundance of elongated benign naked needle nuclei in the background. Smears from some cases of TA revealed isolated and clustered needle cells in low numbers but almost no naked nuclei. Tubulovillous adenoma (TVA) showed features of VA on brush cytology. A hemorrhagic diathesis was distinctly more prominent in VA than in TA. However, focally some red cells were noted in smears from TA. The patterns of TA and VA were otherwise essentially similar with regard to cellularity, individual cell sizes, N/C ratios, and nuclear appearance. PMID- 1935516 TI - Fine-needle aspiration biopsy of papillary thyroid carcinoma: cytologic, histologic, and ultrastructural correlations. AB - Aspiration smears from a series of 21 papillary thyroid carcinomas were studied and a number of morphologic features correlated with the histologic and ultrastructural patterns. These included types of papillary structures, metaplastic cells, grooved and lobulated nuclei, optically clear nuclei, intranuclear inclusions, and macrophages. Generally there was a close correlation between histologic and cytologic findings. The numbers of macrophages and metaplastic cells appeared to be exaggerated in aspiration smears as compared with those seen on histologic sections. Optically clear nuclei were not seen on the air-dried cytologic smears. Grooved nuclei were somewhat difficult to recognize in the aspiration smears, although lobulated nuclei were identified easily. We consider the latter to be a significant feature in the diagnosis of papillary carcinoma. Ultrastructurally grooved nuclei showed a deep linear indentation of the nuclear membranes. Lobulated nuclei were characterized by multiple indentations that divided the nucleus into several lobules. PMID- 1935517 TI - Fine-needle aspiration biopsy of malignant melanoma: a cytologic and immunocytochemical analysis. AB - The immunoreactivity of alcohol-fixed cell blocks from 15 fine-needle aspiration (FNA) specimens of malignant melanoma was investigated using monoclonal antibodies to keratin and vimentin intermediate filaments, melanoma cytoplasmic antigen (HMB-45), and S-100, as well as polyclonal antibodies to S-100. The results were compared with the immunoprofiles obtained using formalin-fixed surgical specimens from 10 of the same patients. In all cases, immunostaining for keratin was negative and immunostaining for vimentin was positive. Immunostaining for HMB-45 was positive in 13/15 aspirates and in 9/10 surgical specimens. Immunostaining for S-100 protein showed the greatest variability in staining, with 5/15 fine needle aspiration biopsies and 9/10 surgical specimens being positive using the polyclonal antibody and only 1/15 FNA specimens and 7/10 surgical specimens being positive using the monoclonal S-100 reagent. Our findings indicate that immunocytochemical studies can be very useful as an adjunct in the FNA diagnosis of melanoma. Also included in our series is an unusual variant of malignant melanoma, the so-called signet ring melanoma. Given the location of the anal verge, the use of immunocytochemical markers was essential in establishing the correct diagnosis in this case. While S-100 protein is of limited value as a marker of melanoma in alcohol-fixed FNA specimens, a definitive diagnosis of malignant melanoma can be made using a panel of antibodies including keratin, vimentin, and HMB-45. PMID- 1935518 TI - Review of the central nervous system cytopathology in human immunodeficiency virus infection. AB - The human immunodeficiency virus (HIV) is a neurotropic retrovirus capable of producing a wide spectrum of central nervous system changes. Nearly 40% of HIV infected patients demonstrate neuropathy ranging from dementia to the opportunistic infections and neoplasia seen in the acquired immunodeficiency syndrome (AIDS). Dramatic increases in the numbers of AIDS cases have allowed for the cytotechnologist and cytopathologist to become acquainted with the various pathologic manifestations of HIV infection. In this review, we are reporting the HIV-related diseases in the central nervous system and the role of diagnostic cytology. PMID- 1935519 TI - Eosinophilic granuloma of lymph node: case report with cytohistologic, immunohistochemical, and flow cytometric observations. AB - A case study of eosinophilic granuloma (Langerhans cell histiocytosis) of lymph node in a 32-year-old white man is presented. Clinical, cytologic, histologic, immunohistochemical, and flow cytometric findings are reported. Intraoperative cytologic findings can serve as valuable adjuncts to the frozen section, in this case serving as the sole method for diagnosis. This case is presented in light of the rarity of node-based eosinophilic granuloma and the absence of flow cytometric immunophenotypic findings in the literature. PMID- 1935520 TI - Cryptococcal thyroiditis: report of a case diagnosed by fine-needle aspiration cytology. AB - A 54-yr-old female diabetic presented with a febrile illness and respiratory distress associated with bilateral alveolar infiltration. The left lobe of the thyroid gland was enlarged and failed to concentrate pertechnetate. The patient was euthyroid. Cryptococcus neoformans was recognized in a fine-needle aspirate and was confirmed by culture; it was also grown in blood culture. Death was attributed to the respiratory condition. This report emphasizes the emergence of mycotic infections of the thyroid and presents an efficient method for their identification. PMID- 1935521 TI - Cytologic features of collagenous spherulosis of the breast. AB - Collagenous spherulosis is generally classified as a component of benign proliferative breast disease. Previous reports have described the histologic features of collagenous spherulosis, but we are unaware of cytologic descriptions of the condition. In this report, the cytologic features of collagenous spherulosis are described and the differential diagnosis is discussed. PMID- 1935522 TI - Needle aspiration cytology of an oncocytic carcinoma of the parotid gland. AB - A needle aspirate biopsy of a parotid neoplasm yielded uniform benign oncocytic cells consistent with oncocytoma. The subsequent surgical specimen demonstrated an oncocytic carcinoma with vascular and perineural invasion. These findings are analogous to those of oxyphilic tumors of the thyroid gland where cytologic features often do not allow for distinction between benign and malignant lesions. PMID- 1935523 TI - Fine-needle aspiration cytology of an unusual primary lung tumor, chondrosarcoma: case report. AB - A case of primary chondrosarcoma of the lung diagnosed by fine-needle aspiration biopsy (FNAB) cytology in a 78-yr-old male is presented. A mass detected on chest x-ray and defined by CT scan was subjected to a preoperative percutaneous fine needle aspiration under fluoroscopic guidance. The distinctive cytologic features of pleomorphic cells nestled in lacunae surrounded by a chondromyxoid background resulted in a diagnosis of chondrosarcoma. The left upper lobectomy specimen confirmed the FNAB diagnosis and identified the tumor as arising from the left upper lobe bronchus. PMID- 1935524 TI - Megakaryocytes in fine-needle aspiration biopsy of breast. AB - An unusual case in which megakaryocytes were found in fine needle aspirate of a breast lesion is reported. The megakaryocytes in the smears were initially mistaken to be malignant cells. However, the cell block sections available later showed normal bone marrow particles, indicating that an inadvertent puncture of a rib was the reason for the presence of megakaryocytes in the smears. PMID- 1935526 TI - The forgotten sciences. PMID- 1935525 TI - Cytological detection of epithelial dysplasia in the oral mucosa using Feulgen DNA-image cytometry. AB - Cytological scrape material of the oral mucosa from 114 patients with epithelial dysplasia and with oral cancer was stained with the Feulgen-reaction and investigated with an image analyzer. The size and the integrated optical density of cell nuclei, and four chromatin texture features were measured. All tumor slides contained cell nuclei with DNA greater than 5c, 16% of the slides had cell nuclei with DNA greater than 8c. A total of 14.5% of the tumor patients showed significantly increased DNA values in nuclei distant from the tumor. Two smears with severe epithelial dysplasia showed nuclei with DNA greater than 5c both in the tumor material and far from the tumor. Texture analysis allowed discrimination between benign, dysplastic and malignant smears. No correlation was found between DNA content and tumor staging. Image cytometry was a reliable method for detecting tumor cells. Epithelial dysplasia in areas distant from the tumor is probably due to "field canceration" of the epithelium. PMID- 1935527 TI - Sublingual nifedipine controversy in drug delivery. AB - Nifedipine, given sublingually, has become increasingly common for treatment of cardiovascular crises. While this may seem an expedient and safe method to reduce blood pressure, controversial issues have surfaced that emphasize the need for cautious drug delivery. Moreover, sublingual administration of nifedipine is not currently approved by the Food and Drug Administration. PMID- 1935528 TI - Skin ulcers of elderly surgical patients in critical care units. AB - The problem of skin ulcers in elderly surgical patients in critical care units is a serious one. Patients with skin ulcers suffer from pain, disfigurement, immobility, septicemia, and sometimes death. Critical care nurses can provide preventive techniques by understanding the complex relationship among the variables causing skin ulcers in elderly patients. The authors describe the variables most related to skin ulcers in elderly surgical patients. PMID- 1935529 TI - Heparin-induced thrombocytopenia and thrombosis. AB - Heparin is one of the most frequently prescribed medications in the United States; yet, a significant number of patients receiving heparin develop heparin induced thrombocytopenia and thrombosis syndrome. This detailed case report demonstrates the significant role nurses play in early detection and prevention of the numerous multisystem complications of this heparin toxicity. PMID- 1935530 TI - The clinical nurse specialist: developing the case manager role. AB - Case management improves cost and quality outcomes in patient care. The clinical nurse specialist is a key person to implement this role and to assure that the nursing focus is on quality outcomes as well as cost factors. PMID- 1935531 TI - Conflict resolution strategies: when ethical dilemmas evolve into conflict. AB - In critical care, ethical dilemmas arise when all duties, rights, and goals cannot be satisfied by the alternatives that are available. Conflicts evolve from ethical dilemmas due to differences in how nurses, physicians, administrators, and patients or families who are involved in a clinical situation assign priorities or interpret roles and responsibilities. This author presents strategies for critical care nurses to use to resolve conflicts that arise in relation to ethical dilemmas. PMID- 1935532 TI - Contracting for visitation with families. AB - Visitation in adult critical care units is an important aspect of patient care, and thus should be incorporated into the patient's plan of care. There is no longer a question as to whether visitation should be liberalized or restricted; instead, visitation is individualized in each situation to best meet the patient's needs. One method of incorporating visitation into the care plan is by contracting with patients and family members. PMID- 1935533 TI - Experimental immunoprevention of type I diabetes mellitus. PMID- 1935534 TI - Pancreas transplantation. PMID- 1935535 TI - Glucose-induced metabolic imbalances in the pathogenesis of diabetic vascular disease. PMID- 1935536 TI - Prediction, prevention, and early intervention in insulin-dependent diabetes. PMID- 1935537 TI - Inflammatory bowel disease. Part II: Clinical and therapeutic aspects. AB - Once regarded as medical curiosities, ulcerative colitis and Crohn's disease have achieved a remarkable change in status recently and today are among the more compelling of all human illnesses. The cause(s) of inflammatory bowel disease (IBD) are not known. Genetic, environmental, microbial, and immunologic factors are involved, but the precise mechanisms are obscure. The incidence of ulcerative colitis is relatively stable, while Crohn's disease continues to increase in frequency. In 10% to 15% of patients, it is hard to differentiate between ulcerative colitis and Crohn's colitis, however, problems with diagnosis usually resolve with time and repeated examinations. In part I of his two-part monograph on IBD, Dr. Kirsner addressed the nature and pathogenesis of the disease. Increased study of ulcerative colitis and Crohn's disease in recent years has generated new knowledge regarding their etiology. Part I focused on microbial, immunologic, and genetic mechanisms of, and the inflammatory process involved in the disease. In this part, Dr. Kirsner deals with the clinical features, course, and management of IBD, based on the author's 55 years of experience with these problems and supplemented by critical examination of the recent (1988-1990) literature. Particular attention is directed to the symptoms and physical findings of ulcerative colitis and Crohn's disease. The laboratory, radiologic, endoscopic, and pathologic features, and the many systemic complications. IBDs are mimicked by several enterocolonic infections and other conditions making differential diagnosis necessary. Inflammatory bowel disease in children and the elderly conforms to conventional clinical patterns modified by the health circumstances of the respective age groups. Because the cause of IBD has not been established, current medical therapy is facilitative and supportive rather than curative. The principles of medical treatment are approximately the same for ulcerative colitis and Crohn's disease. Treatment emphasizes a program rather than a drug and also considers the individuality of the therapeutic response. A clearer understanding of dietary and nutritional needs, including hyperalimentation and electrolyte and fluid balance, aids treatment. Antidiarrheal and antispasmodal preparation and sedatives are prescribed for symptom relief. The bowel inflammation is controlled with sulfasalazine or the newer 5-amino-salicylic acid (5-ASA) compounds, antibacterial drugs for complications of Crohn's disease and IBD, adrenocortical steroids, and the immunosuppressive compounds 6-mercaptopurine (6MP), azathioprine, and cyclosporine, as determined in each patient. The surgical procedures available for treatment of ulcerative colitis include total proctocolectomy and ileostomy or ileoanal anastomosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935538 TI - Clinical electrophysiology of the retinal pigment epithelium. AB - There is no ideal electrophysiological test for retinal pigment epithelial (RPE) function. The light-induced responses (EOG, c-wave, fast oscillation) that require photoreception are not pure RPE signals, and even the widely-used EOG has not been associated with any specific physiological disturbance of the RPE or retina. The discovery of non-photic RPE responses (hyperosmolarity, acetazolamide and bicarbonate) has enhanced the possibility of finding tissue-specific RPE tests, but these responses have yet to be correlated with specific RPE functional activity or pathology. We may face a dilemma in our search for RPE tests, insofar as electrophysiology measures membrane changes, but RPE membrane activity is related only indirectly to many functions of the RPE cell. These concerns notwithstanding, RPE electrophysiology can be a valuable clinical tool if one accounts for the physiological limitations and assets of the procedures. PMID- 1935539 TI - Combined photic and nonphotic electro-oculographic responses in the clinical evaluation of the retinal pigment epithelium. AB - In an attempt to simplify the recording technique in electrophysiologic evaluation of the retinal pigment epithelium, we combined the electro oculographic light rise, hyperosmolarity and acetazolamide responses in a single recording session. Recordings were performed in six normal subjects and in seven patients with diabetic retinopathy or retinitis pigmentosa. In the patients with background diabetic retinopathy, the hyperosmolarity responses were slightly reduced, while the acetazolamide response and the light rise was normal. In the patients with proliferative diabetic retinopathy, the hyperosmolarity response and light rise were remarkably reduced, while the acetazolamide response was normal. In the patients with retinitis pigmentosa, the hyperosmolarity response and light rise were decreased, while the acetazolamide response was normal. Despite a small study population, we concluded that the clinical results from our combined recording protocol were essentially the same as those reported for each response separately. Because this recording technique simplifies electrophysiologic evaluation of the retinal pigment epithelium, it may help clarify the mechanisms or localization of retinochoroidal and pigment epithelial diseases. PMID- 1935540 TI - Intraoperative retinal light damage reflected in electrophysiologic data. AB - In a series of 30 unilaterally pseudophakic patients, electroretinograms and electrooculograms were recorded 6 months postoperatively. The unoperated on fellow eyes served as controls. High intraoperative retinal light exposure (3.4 7.3 mW/cm2, Zeiss OPMI6 operating microscope) caused a substantial reduction of electrophysiologic potentials. Light protection prevented deterioration of electroretinogram and electro-oculogram potentials; reducing the bulb voltage, tilting the axis of illumination, filtering short wavelengths and the use of light shields resulted in 4-log-unit lower intensities (0.8-3.7 microW/cm2). PMID- 1935541 TI - Longitudinal electroretinogram study in a patient with metallosis oculi. AB - Serial electroretinograms were obtained from a patient with visual loss secondary to an intraocular metallic foreign body. Six days after the injury, the acute phase electroretinogram was larger in the affected left eye. During the following months, the electroretinogram amplitude declined steadily in the affected eye to values well below normal. At 9 months, electroretinogram amplitudes were approximately 50% compared with those in the normal eye. Clinical signs confirmed the need for surgery, and the foreign body was removed. Visual acuity in both eyes remained essentially normal, and electroretinogram amplitudes stabilized over subsequent months. Approximately 8 months after surgery, dark-adaptometry testing showed a 1-log unit elevation of absolute threshold in the affected eye, and Rmax in the affected eye was 42% of that in the uninjured eye. PMID- 1935542 TI - Visual evoked potentials in macular hole. AB - Pattern reversal visual evoked potentials (VEPs) with checks of 50' and 12' were recorded in 15 patients with idiopathic unilateral macular hole. VEPs from the affected eyes were reduced in amplitude compared with those from the fellow eyes, especially with checks of 12' (percentage of the amplitude in the affected eye to that in the fellow eye was 86% +/- 19% with checks of 50' and 61% +/- 35% with checks of 12'). The latencies showed no statistically significant difference between the affected and the fellow eyes, although a marked interocular delay was found in a few patients. The degree of amplitude reduction and interocular delay had no relation to the size of the macular hole or visual acuity. The effects of experimental scotomata of various sizes on the VEPs, which were evaluated in nine normal subjects, were also variable among the subjects. We conclude that although the macula predominantly participates in the pattern VEP, an estimation of the extent of macular pathology from the VEP changes may be difficult because the VEP changes induced by a macular hole have wide individual variation and have no relation to the size of the hole. PMID- 1935543 TI - The intrasession repeatability of pattern electroretinograms and the effects of digital filtering. AB - Transient pattern electroretinograms were recorded in 12 normal young volunteers with the use of 12' and 30' checkerboard stimuli and 1 c/deg and 2.5 c/deg vertical gratings. The intrasession repeatability of pattern electroretinograms was determined by employing alternative statistics to the frequently used correlation coefficients. Comparisons were made with the repeatability of cone electroretinograms elicited by ganzfeld stimulation. The coefficient of repeatability was substantially lower (better) for pattern electroretinogram b wave implicit times than for a-wave implicit times and b-wave amplitudes, the latter having high coefficients of repeatability. Cone electroretinograms had better repeatability with respect to all three parameters. Digital filtering using a bandpass of 1-40 Hz was applied to the original pattern electroretinograms recorded with a bandpass of 1-250 Hz. Although peak definition was generally enhanced, repeatability did not show marked improvement. Differences between broadband analogue-filtered pattern electroretinograms and the same responses with high-frequency noise removed by digital filtering need to be taken into account. The coefficient of repeatability statistic appears to facilitate the assessment of pattern electroretinograms and permits the comparison of the repeatability of both implicit time and amplitude parameters irrespective of absolute values. The implications of the relatively poor repeatability of pattern electroretinogram b-wave amplitudes for clinical applications need to be considered. PMID- 1935544 TI - Luminance-unbalanced pattern onset-offset electroretinogram and visual evoked cortical potential. AB - The effects of a luminance-unbalanced pattern onset-offset mode of stimulation on electroretinograms and visual evoked cortical potentials were investigated. With the use of originally devised software, only offset luminance was varied from 14.7 to 62.3 cd/m2. A vertical grating pattern (1.5 c/deg, 38.8 cd/m2 mean luminance, 0.95 contrast) was presented for 260 ms and was absent for 260 ms to normal subjects. With an increase in the luminance level of the offset pattern from the lowest level, the amplitude of the onset electroretinogram increased by degrees, while that of the offset electroretinogram gradually decreased. Conversely, onset visual evoked cortical potential responses decreased gradually, and offset visual evoked cortical potentials increased correspondingly. Furthermore, the spatial tuning of the onset pattern electroretinogram was already ambiguous, even when there was only a 4-cd/m2 difference between onset and offset pattern luminances. Thus, luminance control is indispensable for pattern onset-offset stimulation. PMID- 1935545 TI - Dark-adapted luminance-response functions with skin and corneal electrodes. AB - Normative dark-adapted electroretinograms were recorded simultaneously with a skin electrode and corneal electrode for varying stimulus intensities. The electroretinogram b-wave amplitudes for each electrode were fitted by the Naka Rushton equation, and the parameters Vmax, K and n were evaluated. A comparison of parameters between the two electrodes showed a significant difference for Vmax and K but not for n. Vmax was approximately eight times smaller and K was 0.3 log unit smaller for the skin electrode than for the corneal electrode. B-wave amplitude and implicit time were also compared between the two electrodes. The b wave amplitude ratio of the corneal electrode to that of the skin electrode increased with luminance and ranged from 1.83 to 7.68. Overall, b-wave implicit time for the skin electrode was approximately 10 ms shorter than that of the corneal electrode. PMID- 1935546 TI - The influence of adaptation on the oscillatory potentials of the human electroretinogram. AB - The influence of adaptation on the oscillatory potentials of the human electroretinogram was studied in the domains of frequency and time. The amplitude of OP1 to OP4, the summed amplitude of OP1 to OP4, as well as the area, decreased from dark adaptation to light adaptation. With increasing intensities of background illumination, they increased slightly and appeared to decrease with the strongest background illumination. The implicit time of oscillatory potentials 3 and 4 increased with stronger background illumination and decreased with the strongest background illumination. The results of the dominant frequency and the total power of the OPs correspond to the results in the time domain. The dominant power decreased from dark adaptation into light adaptation and did not show any systematic changes with increasing intensity of background illumination. PMID- 1935547 TI - Simulation of the electroretinographic slow PIII component by injection of K+ free Ringer's solution in the frog retina. AB - The light-induced hyperpolarization of the photoreceptor results in a decrease in extracellular potassium ion concentration, [K+]. A decrease in [K+] in the photoreceptor layer was caused by injecting a small amount of K+-free Ringer's solution in the isolated frog retina, and the distribution of the field potential as induced by K+-free Ringer's solution was mapped. The depth profile of the response resembled that of the slow PIII component of the electroretinogram. These results support the notion that the slow PIII is generated by the Muller cells as they hyperpolarize in response to a light-induced decrease in [K+] in the photoreceptor layer. PMID- 1935548 TI - Abstracts of the 31st meeting of the Association for Eye Research including the annual meeting of the European Club for Ocular Fine Structure. Bad Honnef, Germany, 14-18 October 1990. PMID- 1935549 TI - Gestational diabetes. PMID- 1935551 TI - Gestational diabetes mellitus. PMID- 1935550 TI - A unique collaborative network for diabetes education. AB - The DCNH is a unique collaborative venture in outpatient diabetes education. We believe it can serve as a model for rapidly developing standardized diabetes education in geographically dispersed communities. The heart of the organization is the educators' meeting, which enables an extensive sharing of ideas and information that benefit all patients in the region. The features crucial to our success have been (1) administrative leadership with a nursing management or educator background, (2) data collection and analysis, (3) local development of an educational curriculum based on ADA standards, and (4) centralized medical and administrative directors who are available to meet individual program needs. However, we are most indebted to the farsighted and strong commitment of our member hospitals to diabetes care in their communities. PMID- 1935552 TI - From diagnosis to home management: nutritional considerations for women with gestational diabetes. AB - Each year 90,000 women in the United States are diagnosed with gestational diabetes. The transition from diagnosis to home management is a time of high stress for these women. Anxiety may lead to difficulty with self-care in general and the diabetic diet in particular. Follow-up education by a diabetes educator can help clients plan meals that comply with the nutritional meal plan without disrupting the family's eating habits. The client should be taught to measure portions, to recognize sugar as an ingredient in foods and medicines, and to deal with special occasions such as holiday meals, travel, and illness. If extended home care is not feasible, the creative diabetes educator will devise other educational opportunities, such as home videos, telephone support networks, special childbirth classes for women with gestational diabetes, and luncheon meetings at which nutritionally correct meals are served. PMID- 1935553 TI - Euglycemic control of gestational diabetes mellitus by specific dietary manipulation: a case study presentation. AB - Gestational diabetes is the most common complication of pregnancy. If maternal hyperglycemia is not well controlled, excess glucose is transmitted to the fetus, which can lead to fetal macrosomia and maternal and fetal complications. Dietary treatment for gestational diabetes varies among practitioners. A case review is presented of a 32-year-old white woman with gestational diabetes whose condition was complicated by her blood glucose intolerance to lactose in milk. By following a carefully monitored regimen using specific dietary manipulation to maintain normoglycemia, the woman was able to deliver a normal, healthy baby by spontaneous vaginal delivery. PMID- 1935554 TI - Spaseeba balshohyi--kharohshiyi! (Thank you very much--it was great!). AB - In January 1990, as partial fulfillment of a 5-year contract to train Soviet health professionals, a six-person team from the International Diabetes Center went to Moscow to present a program on diabetes education and management to 45 of the USSR's leading endocrinologists and 20 physicians from Moscow's Central Institute for Advanced Medical Studies. The IDC team found a nation faced with major problems and shortages but filled with physicians and patients eager to learn and ready to act. Diabetes education as practiced in the United States is unknown in the Soviet Union, but through training programs such as this, the Soviets are updating and expanding their knowledge of diabetes education and management. PMID- 1935555 TI - Addressing attitudes during diabetes education: suggestions from adult education. AB - Suggestions from adult education can improve the effectiveness of diabetes education programs. While information and knowledge are noted as important factors in diabetes education, the literature indicates that they are insufficient to insure improved treatment outcomes. Research suggests that addressing psychosocial variables can improve diabetes education effectiveness. Although there are a multitude of psychosocial variables, attitude is consistently identified as an important contributor to positive diabetes management. Practical suggestions from adult education are offered to improve the learner's attitude about diabetes, the learning process, and the instructor. PMID- 1935556 TI - Understanding the use of the exchange lists for meal planning in diabetes management. AB - The Exchange Lists for Meal Planning has been in existence since 1950 and was updated in 1976 and 1986. The lists were designed to provide a universal system for the nutrition management of diabetes mellitus. The current edition emphasizes a high-carbohydrate, low-fat diet and is widely used by persons with diabetes and by diabetes educators. To use the exchange lists, the educator must understand how to develop a meal plan. The meal plan serves as the tool to help patients select appropriate foods and amounts. The necessary steps for establishing the meal plan are outlined, and a suggested sequence for educating persons with diabetes in the use of the lists is presented. PMID- 1935557 TI - Coordination of care for the pregnant woman with diabetes in a high-risk setting. PMID- 1935558 TI - The changing insulin market. AB - The discontinuation of all U-40 insulins as well as all protamine zinc insulins will require you, as a diabetes educator, to educate patients about their insulin needs and the proper use of alternative insulins and insulin syringes. Table 2 is a summary of all of the insulins presently available in the United States as of December 1991. Now that the insulin diabetes product list has been shortened, we can hope that this will decrease some of the confusion in terms of insulin products available. Note, however, that in the future we may have additional insulins available in terms of different mixtures of regular and NPH. We also hope to have available within the relatively near future insulin analogs that have different amino acid sequences that cause insulins to have a much more rapid pharmacologic effect than is presently possible. Note also that regardless of the type of insulin used, the objective of insulin therapy in patients with diabetes is to bring blood glucose levels as close to normal as possible, while at the same time allowing the patient to live as flexible and normal a life-style as possible. PMID- 1935559 TI - [Association kinetics of muscle glycogen phosphorylase B induced by an allosteric activator]. PMID- 1935560 TI - [A quantitative method of assessing the strength of binding of a ligand with an enzyme based on proteolytic digestion. Binding of FMN with muscle glycogen phosphorylase B]. PMID- 1935561 TI - [Effect of an epiphyseal polypeptide preparation on life expectancy and frequency of spontaneous tumors in aged female rats]. PMID- 1935562 TI - [GABA-immunoreactive neurons participate in centrifugal innervation of the frog olfactory bulb]. PMID- 1935563 TI - Unrecognized left ventricular dysfunction in an apparently healthy alcohol abuse population. AB - To examine effects of chronic alcohol abuse on left ventricular function, 162 otherwise relatively healthy alcohol abusers, having been admitted to a rehabilitation program, underwent cardiac evaluation including chest X-ray, electrocardiogram, and radionuclide angiography after 2 weeks abstinence. Twenty nine of the 162 alcoholic subjects (18%) with left ventricular dysfunction were identified. Twenty-two had regional wall motion abnormalities, suggesting a localized process, of whom 12 also had depressed ejection fractions. Seven others had a depressed ejection fraction alone with a more global myopathic process. Only 4 of these 29 patients had any history suggesting prior heart disease. Two of the 29 had Q-waves greater than or equal to 0.4 s and 8 had an abnormal cardiothoracic ratio on chest X-ray. Chronic alcohol abusers appear to be at relatively high risk for left ventricular dysfunction; most of which is unrecognized. Routine screening methods failed to identify 85% of our subjects who later were recognized by radionuclide angiography. Since historical and electrocardiographic abnormalities are often absent in this population, detection of left ventricular dysfunction by other methods such as radionuclide angiography must be used. PMID- 1935564 TI - Effects of chronic marijuana use on testosterone, luteinizing hormone, follicle stimulating hormone, prolactin and cortisol in men and women. AB - To investigate possible effects of chronic marijuana use on reproductive and stress hormones, we assayed testosterone, luteinizing hormone, follicle stimulating hormone, prolactin, and cortisol in 93 men and 56 women with a mean (+/- S.E.) age of 23.5 +/- 0.4 years. Hormone values were compared among groups of subjects stratified according to frequency of marijuana use (frequent, moderate and infrequent; N = 27, 18, and 30, respectively) and non-using controls (N = 74). Chronic marijuana use showed no significant effect on hormone concentrations in either men or women. PMID- 1935565 TI - Is the strength and the desirability of alcohol-related expectancies positively related? A test with an adult Swedish sample. AB - Workers at the Swedish Telephone Company participated in the present study to explore the alcohol-related expectancies for a general sample of Swedish citizens and relate these expectancies to various background factors and whether the expected effects of alcohol also were desired effects. A slightly modified version of the Alcohol Expectancy Questionnaire (AEQ) was used and data were analyzed in terms of six general factors. Results indicated that men expected more sexual enhancement than women and that high consumers expected more strong effects for all six factors than the low consumers. Men further rated both sexual enhancement, physical and social pleasure, and social assertiveness as more desirable effects than did women, and the high consumers rated all six effects as more desirable than the low consumers. Results are discussed in terms of expectancies as causes of drinking. PMID- 1935566 TI - Trends in diagnosed drug problems among newborns: United States, 1979-1987. AB - Between 1979 and 1987, there was an estimated 361% increase in the number of drug affected newborns discharged from the 6000 non-federal, short-stay hospitals in the United States. Per 10,000 newborns, the rate increased 339%, mostly occurring after 1983. The estimated number of drug affected newborns in 1987 was about 13,000 (95% confidence interval: 10,000-15,000). Recognizing that underreporting could have occurred, multiplicative correction factors derived from the literature were employed to produce 'adjusted' estimates. While somewhat arbitrary, the number of drug-affected newborns, adjusted for underreporting, was about 38,000 (95% confidence interval: 30,000-45,000). Both adjusted and unadjusted estimates of the numbers of newborns identified as drug-affected by the present study is much smaller than most of the estimates reported in the literature. Possible reasons for this finding are discussed. PMID- 1935567 TI - Knowledge and views on drug abuse of primary health care workers in Nigeria. AB - Primary health care (PHC) in Nigeria (as in many developing countries) relies heavily on paramedical personnel. Using a self-report structured questionnaire design, 207 PHC workers were assessed on their knowledge and views about drug and alcohol abuse. PHC workers with previous exposure to some form of drug abuse training were significantly more likely to be aware of the correct usage for the term 'drug abuse', although the whole range of drugs of abuse/dependence was much less well appreciated. Drugs reported by the PHC workers to be commonly abused in the study area were in keeping with previous findings on drug abuse in the country. However, 75.4% of the PHC workers perceived drug abuse as a low grade problem, in contrast to recent reports, of the increasing magnitude of drug abuse problems in the country. About one fifth of PHC workers were of the opinion that drug abusers should be punished. Only 35 (16.9%) of those who indicated the need for treatment mentioned that this could be carried out by PHC personnel. Many of the PHC workers showed limited knowledge of factors associated with drug abuse and on the scope of preventive strategies against drug abuse. Suggestions are made on the short and long term training needs of the PHC workers in order to ensure the successful incorporation of drug abuse treatment and prevention programmes into the PHC programme in Nigeria. PMID- 1935568 TI - The amount of alcohol intake and some associated factors in a representative sample of 691 French boys aged 13-18. AB - As a first step in a longitudinal study, we studied a sample of 691 French boys selected at random so that the region, the type of dwelling, and the profession of the wage-earner agreed with the latest official census. About 200 questions were asked by professional interviewers. The amount of alcohol intake was calculated from questions concerning type and amount of drinks consumed on all possible occasions. The mean yearly alcohol consumption was 0.91 liters of pure ethanol at 13-14 years, 2.08 at 15-16, and 5.88 at 17-18 (national average in Frenchmen 15 years and over: 16.5). Alcohol intake increases significantly with frequency of cafe and public dance attendance in all three age groups. Other factors, such as cigarette smoking, pop concerts or night club attendance, familial environment, show significant difference in only one or two age groups. Type of habitation, number of siblings, church attendance, etc., are not significant. PMID- 1935569 TI - Alcohol drinking among Moslem and Druze adolescents in Israel in 1990. AB - This article describes the Moslem and Druze parts of a survey conducted in the north of Israel during spring 1990 in order to investigate alcohol drinking habits of Moslem, Druze and Jewish high school students and to draw implications for prevention efforts. Of a general sample of 2763 students, 932 Moslem and 215 Druze adolescents were drawn from junior and senior high schools in a Druze village, several Moslem villages, an Arab town, and a mixed Arab-Jewish town. This is the first epidemiological study among students from those sectors in Israel. Involvement with alcohol was greatest among Druze males, lower by Moslem males from an Arab town and Moslem villages, and lowest by Moslem students in a mixed Arab-Jewish town. Druze students reported a higher rate of father's drinking than Moslem students did. Prevention efforts among these populations are discussed. PMID- 1935570 TI - Alcohol, tobacco and illicit drug use amongst nurses: a Scottish study. AB - This paper examines patterns of self-reported alcohol, tobacco and illicit drug use amongst a representative sample of 600 qualified nurses in the Lothian Region of Scotland. General levels of alcohol use were not exceptional. Even so, levels of tobacco smoking and the use of illicit drugs were higher than for the general population. Female psychiatric nurses were significantly more likely than female medical or surgical nurses to smoke tobacco, to drink heavily and to have experienced adverse alcohol-related consequences. PMID- 1935571 TI - Teenagers and alcohol: results of a Scottish national survey. AB - During 1990 a survey was conducted of the self-reported drinking habits and alcohol-related knowledge and beliefs of a national sample of 7009 Scottish teenagers. The study group were age 14-16. Results indicated that only 3% of respondents had never consumed alcohol. The great majority of teenagers reported consuming only moderate quantities of alcohol. Even so 18.9% of males and 10.3% of females reported consuming 11 or more units on their last drinking occasion. The proportion of teenagers classified as 'heavy drinkers' increased markedly between the ages of 14 and 16. This study confirmed earlier findings indicating that Scottish teenagers are more likely than those in England to drink heavily and rather less frequently. PMID- 1935572 TI - Relationship between hepatic histology and conventional biochemical liver function test in chronic alcoholic patients. AB - This paper explores the relationship between hepatic histology and conventional biochemical liver function tests in 125 chronic alcoholic patients. On the basis of the results obtained, it is suggested that abnormal biochemical liver function tests may offer important clues for further invasive investigations to establish the diagnosis of alcoholic liver disease. PMID- 1935574 TI - Stereoselectivity of glutathione conjugation in vivo, in the perfused liver and in isolated hepatocytes. PMID- 1935573 TI - Metabolism of azo dyes: implication for detoxication and activation. AB - Azo dyes are consumed and otherwise utilized in varying quantities in many parts of the world. Such widely used chemicals are of great concern with regard to their potential toxicity and carcinogenic properties. Their metabolism has been studied extensively and is significant for detoxication and metabolic activation. Both oxidative and reductive pathways are involved in these processes. The majority of azo dyes undergo reduction catalyzed by enzymes of the intestinal microorganisms and/or hepatic enzymes including microsomal and soluble enzymes. The selectivity of substrate and enzyme may to a large extent be determined by the oxygen sensitivity of reduction since a normal liver is mainly aerobic in all areas, whereas the microorganisms of the lower bowel exist in an anaerobic environment. However, it should be pointed out that the pO2 of centrilobular cells within the liver is only a fraction that of air, where pO2 = 150 torr. Therefore, an azo dye reduction experiment performed aerobically may not be an accurate predictor of reductive metabolism in all areas of the liver. Many of the azo dyes in common use today have highly charged substituents such as sulfonate. These resist enzymic attack and for the most part are poorly absorbed from the intestinal tract, providing poor access to the liver, the major site of the mixed function oxidase system. Lipophilic dyes, such as DAB, which are often carcinogenic, readily access oxidative enzymes and are activated by both mixed function oxidase and conjugating systems. Reduction of the carcinogenic dyes usually leads to loss of carcinogenic activity. By contrast, most of the highly charged water-soluble dyes become mutagenic only after reduction. Even then, most of the fully reduced amines required oxidative metabolic activation. An outstanding example is the potent human bladder carcinogen benzidine, which derives from the reduction of several azo dyes. Many problems regarding mutagenic and carcinogenic activation remain to be solved. At the present time, it is apparent that both oxidative and reductive pathways yield toxic products. Toxicologic assessment of azo dyes must consider all pathways and particularly the oxygen sensitivity of azoreduction. This is critical in the treatment of waste from chemical plants where there is a great need for soil bacteria which catalyze reduction aerobically. Consideration of secondary pathways are also of great concern. For example, azoreduction of carcinogenic dyes such as DAB removes carcinogenic activity although oxidative metabolism of the primary amines yield mutagenic products. Such apparent dilemmas must be dealt with when considering metabolism/toxicity relationships for azo dyes. PMID- 1935575 TI - Stereoselective glutathione conjugation by subcellular fractions and purified glutathione S-transferases. PMID- 1935576 TI - Species differences in metabolism and pharmacokinetics: are we close to an understanding? PMID- 1935578 TI - Metabolic disposition and development of new chemopreventive retinoids. PMID- 1935577 TI - Perfluorochemical erythrocyte substitutes: disposition and effects on drug distribution and elimination. AB - As a result of their ability to transport oxygen, PFC emulsions are being investigated for possible use in a wide variety of conditions. The recent FDA approval of F-DA to diminish myocardial ischemia during angioplasty is the first marketing approval for such a product in the world. The many potential uses of such products may result in their common application in the future, especially as new and better products are developed. The elimination, distribution, and tissue retention of PFC emulsions as well as the physiological changes that occur upon their administration have been the subject of many investigations. The results indicate that these agents may influence the pharmacokinetic properties of other drugs by a wide variety of mechanisms. Several studies have shown significant, but not necessarily consistent, changes in drug elimination and distribution following PFC emulsion infusion. Changes appear dependent on the drug examined, emulsion utilized, degree of blood exchange, species utilized, and the controls chosen for comparison. Often, the changes are time dependent indicating the importance of conducting long-term studies. While PFC emulsions do not appear to alter renal elimination of drugs, several studies have demonstrated that these agents have the potential to induce drug metabolism from several days to possibly months after exposure. Observed changes in drug volumes of distribution, which are often time dependent, may be due to changes in normal drug transport throughout the circulation and/or changes in membrane permeability and cell transport mechanisms. Changes in drug transport may result from depletion of plasma proteins or increases in alpha 1-acid glycoprotein levels due to trauma or PFC emulsion effects. The binding of drugs by PFC emulsion droplets varies greatly and PFC emulsion components displace some plasma protein bound drugs. The wide variability in the results and conclusions of the pharmacokinetic studies conducted to date emphasize the importance of utilizing adequate controls to identify which alterations are PFC emulsion specific. PMID- 1935579 TI - Helping patients to make the best use of medicines. PMID- 1935580 TI - Oral contraception in the perimenopause. PMID- 1935581 TI - Underused: intermittent self catheterisation. PMID- 1935582 TI - Imipenem + cilastatin--a new type of antibiotic. PMID- 1935583 TI - Gestrinone (Dimetriose)--another option in endometriosis. PMID- 1935584 TI - Colfosceril palmitate (Exosurf)--artificial surfactant for immature lungs. PMID- 1935585 TI - Pravastatin (Lipostat)--another statin for lowering cholesterol. PMID- 1935586 TI - Diethylstilboestrol--effects of exposure in utero. PMID- 1935587 TI - Mefloquine--a new antimalarial. PMID- 1935588 TI - Practical aspects of blood pressure management. PMID- 1935589 TI - Temocillin injection for gram-negative infections only. PMID- 1935590 TI - Economic prescribing. PMID- 1935591 TI - Tibolone (Livial)--a new steroid for the menopause. PMID- 1935593 TI - Pergolide (Celance)--a third dopamine agonist. PMID- 1935592 TI - Acemetacin (Emflex)--yet another NSAID. PMID- 1935594 TI - Oxitropium (Oxivent). PMID- 1935595 TI - Zidovudine in HIV infection. PMID- 1935596 TI - Hyperventilation syndrome--not to be dismissed. PMID- 1935597 TI - Junifen suspension--ibuprofen for febrile children. PMID- 1935598 TI - Clinical psychology and general practice. AB - General practitioners who secure the collaboration of a clinical psychologist in treating patients, especially in a community setting, are likely to benefit the patients and themselves. Transfer of skills may be an important way for the two professions to collaborate. Health promotion could be a fruitful field for collaboration but has so far been little explored. PMID- 1935599 TI - Oral hypoglycaemics for diabetes: when and which? PMID- 1935600 TI - Postscript: fibrinolysis after acute myocardial infarction. PMID- 1935601 TI - Recently introduced products. PMID- 1935602 TI - Octreotide for endocrine tumours. PMID- 1935603 TI - Day case surgery. PMID- 1935604 TI - Constructing a practice formulary: a learning exercise. PMID- 1935605 TI - The management of extra-pulmonary tuberculosis. AB - Most cases of extra-pulmonary tuberculosis respond well to chemotherapy. The standard regimen is isoniazid + rifampicin daily for 6 months, with the addition of pyrazinamide for the first 2 months. Chemotherapy is given for 9 or 12 months in meningitis, and in some cases of lymphadenitis and bone and joint disease. If initial drug resistance is suspected, either streptomycin or ethambutol should be added to the first phase of treatment. Only a minority of cases need surgical treatment but surgical diagnostic procedures are often useful. Corticosteroids are not recommended for routine use but can be valuable in lymphadenitis, meningitis, pericarditis and genito-urinary disease. PMID- 1935606 TI - What chiropody offers. PMID- 1935607 TI - Shedding light on seasonal affective disorder. PMID- 1935608 TI - Idiopathic oedema: non-drug treatment first. PMID- 1935609 TI - Readers' comments: home oxygen for infants. PMID- 1935611 TI - [The beginning and the ending of a relationship]. PMID- 1935610 TI - [Communication training program]. PMID- 1935613 TI - [Guidance and support of families in psychiatric admission wards]. PMID- 1935612 TI - [Experiencing nursing in the acute psychiatric field]. PMID- 1935614 TI - [Psychotropic drugs in emergency situations]. PMID- 1935616 TI - [The situation at the admission of adolescents in acute crises]. PMID- 1935615 TI - [The psychiatric treatment of recurrently aggressive patients]. PMID- 1935617 TI - [Ethics commissions in the Federal Republic of Germany]. PMID- 1935618 TI - [The difficult patient]. PMID- 1935619 TI - [Integration of refugees. Report on a model project of a year long adaptation measure for refugees to obtain permission to call themselves professional nurses]. PMID- 1935620 TI - [On the theory of nursing the sick. A critical understanding of the nursing theoretical framework of Liliane Juchli's book "Nursing"]. PMID- 1935621 TI - [Experiences of a pediatric nurse in a premature intensive care unit. Emphasis in the care of premature infants with respiratory distress syndrome]. PMID- 1935622 TI - [Experiences of a pediatric nurse in a premature intensive care unit. Emphasis in the nursing of premature infants with respiratory distress syndrome]. PMID- 1935623 TI - [Polyneuropathy and central nervous system diseases before and after heart transplantation. Is cyclosporin neurotoxic?]. AB - In a cross-sectional study, 52 patients (44 men, 8 women, mean age 50.6 [19-68] years) were investigated clinically and electrophysiologically for evidence of peripheral and central nervous system damage before and after heart transplantation. 20 patients were investigated before heart transplantation (group 1), 16 at 7 days to 5 months after transplantation (early post-operative group; group 2) and 16 at 6 to 32 months after transplantation (late post operative group; group 3). Nerve conduction studies (median, peroneal and sural nerves) revealed polyneuropathy in 14 out of 16 patients in group 2, significantly more than in group 1 (11 out of 19) and group 3 (9 out of 16). The mean blood cyclosporin concentration was 656 ng/ml in group 2 and 409 ng/ml in group 3 (P less than 0.001). Patients in group 3 with polyneuropathy had significantly higher cyclosporin concentrations than patients without polyneuropathy (505 vs 284 ng/ml; P less than 0.01). Among patients who had undergone operations, there were no noteworthy differences between the mean cyclosporin concentrations and clinical data in those with or without central nervous system lesions. There is preliminary evidence of a neurotoxic effect of cyclosporin on the peripheral but not the central nervous system. PMID- 1935624 TI - [Inferior vena cava compression syndrome in cystic kidney. Duplex ultrasonic diagnosis]. AB - Four months after renal transplantation for polycystic renal degeneration a 38 year-old man developed breathing-related pain in the left upper lung and a sinus tachycardia (130/min). Lung perfusion scintigraphy demonstrated pulmonary emboli from an acute venous thrombosis of the left lower leg. Polycythaemia and impairment of clot-inhibiting factors were excluded. Ultrasound examination of the abdomen revealed stenosis of the inferior vena cava (IVC) distal to the hepatic veins, dorsal to the liver and ventral of a huge right polycystic kidney which had been left in situ at the time of the renal transplantation. Duplex sonography demonstrated a band-like flow profile in the region of the stenosis. Blood flow was clearly increased (0.62 m/s) and not affected by either heart rate or breathing movements. The findings were confirmed by angiography. The right kidney, weighing 5 kg, was removed at surgery. The IVC stenosis was postoperatively found to be relieved and duplex sonography gave normal findings. PMID- 1935625 TI - [Monosymptomatic endemic sprue as a cause of iron deficiency anemia]. AB - For about two years a 23-year-old woman, without symptoms and of normal weight, had been known to have an iron deficiency anaemia (Hb 56 g/l; after oral iron substitution 100 g/l; mean corpuscular volume 66.7 fl, ferritin 5.0 micrograms/l). Gynaecological examination was normal. Radiography of the small intestine revealed coarse rugal pattern of the duodenum. Endoscopically obtained duodenal biopsy demonstrated villous atrophy. Elevated anti-gliadin antibody titres (IgG 49.9 U, IgA 52.3 U), as well as the response to a gluten-free diet confirmed the diagnosis of monosymptomatic coeliac disease. Although anaemia is one of the characteristic features of coeliac disease, it is rare as the only sign. The risk of delayed diagnosis is especially high in women before menopause. PMID- 1935627 TI - [Pathogenesis and diagnosis of acute pulmonary failure]. PMID- 1935626 TI - [Brain abscess as a complication of Osler's disease with lung involvement]. AB - Eight months after sustaining a reversible left motor hemisyndrome, predominantly of the arm, a 47-year-old man known to have hereditary haemorrhagic telangiectasia (Osler's disease) again developed neurological symptoms (headache, vertigo, unsteady gait) with fever (up to 38.5 degrees C). Clinical features and findings on computed tomography indicated a cerebellar abscess. This was resected because it continued to enlarge despite antibiotic treatment with daily 2 g ceftriaxone and twice daily 0.5 g ornidazole. As another manifestation of Osler's disease further tests revealed an arteriovenous malformation (2.5 x 2.0 cm) in the right upper lobe of the lung, presumably the cause of the cerebral abscess. After wedge resection of the anterior upper lobe segment the further course was without complications. PMID- 1935628 TI - [Heroin addiction. I. Extension, pharmacological bases and effects of heroin]. PMID- 1935629 TI - [Duties of a hospital admissions physician when hospital is filled beyond capacity]. PMID- 1935630 TI - [Osteoporosis in men]. PMID- 1935631 TI - [Chemoprophylaxis in Haemophilus influenzae type B meningitis]. PMID- 1935632 TI - [CO2-induced acral blood flow and the oxygen partial pressure in arterial occlusive disease]. AB - The effect of CO2-containing water on foot skin blood flow (laser-Doppler flux) and transcutaneous oxygen partial pressure (tcpO2) was measured in 16 patients (15 men and 1 woman; mean age 58 [49-71] years) with peripheral arterial occlusive disease (stage II of Fontaine: bilateral occlusions of the superficial femoral arteries). After 30 minutes lying down and 10 minutes sitting up, one lower leg was immersed in fresh water, the other in CO2-containing water (1400 mg CO2/kg H2O), both at 34 degrees C for 20 minutes. On the next day the measurements were repeated changing sides. Skin blood flow of the dorsum of the foot and rhythmic flow oscillations (flux motion) increased threefold in the CO2 water-bath, after a latency period averaging 2 minutes, within 3 minutes from 1.1 to 3.9 relative units (P less than 0.005). Average tcpO2 increased during the bath in CO2 water by 9 mm Hg (P less than 0.005). There was no change in fresh water. The increase in cutaneous blood flow and oxygen partial pressure, which persisted throughout the period in CO2 water, is interpreted as an increase in microcirculation and can explain part of the effectiveness of this largely empirical treatment. PMID- 1935633 TI - [Hygienic and economic significance of sewer drainage in hospitals. Architectural changes in the guidelines of the Federal Health Office]. AB - The hygienic importance of barrier zoning in hospitals has been evaluated on the basis of the relevant international literature between 1970 and 1989. There have been only a very few pertinent publications and in none has there been any pointer which would support the hypothesis of barriers having an infection preventing effect. Using four University Hospitals in Baden-Wurtemberg as paradigms, a model was prepared for calculating what space and cost savings were possible, if a simpler system could be installed, instead of the one demanded under federal regulations and already planned for the four hospitals. It was found that it would save a realizable area of 319,5 m2 at a potential cost saving of DM 1,138,335. By dispensing with hygienically not justifiable building work at the planning stage of new hospitals considerable greater costs could be avoided. PMID- 1935634 TI - [Chronic purulent, draining, indolent pancreatic head pancreatitis with extrahepatic cholestasis]. AB - Over the period of two weeks a 19-year-old man developed gradually increasing painless jaundice with dark urine and light-coloured soft stools (6-7 times daily), as well as loss of appetite, nausea and nagging itch. Biochemical tests indicated marked cholestasis (alkaline phosphatase 800 U/l, gamma-GT 206 U/l). Abdominal ultrasound examination revealed high-grade stenosis of the distal choledochal duct caused by an enlargement of the head of the pancreas and computed tomography confirmed a tumour in this location. Endoscopic retrograde cholangiopancreatography demonstrated filiform stenosis of the major pancreatic duct and prepapillary stenosis of the choledochal duct. Several needle biopsies failed to establish a definitive diagnosis. A Whipple operation was performed: the stomach was preserved but about 40% of pancreatic tissue resected. Histologically there was chronic suppurative pancreatitis of the head of the pancreas. The patient was symptom-free 6 months after the operation. The case illustrates that it is not always possible in a painless pancreatic tumour to distinguish between pancreatitis and malignant tumour. PMID- 1935635 TI - [Therapy of acute pulmonary failure]. PMID- 1935636 TI - [Heroin addiction. II. Therapy and prevention]. PMID- 1935637 TI - [Prescribing substitute drugs for drug dependence. Decision of the Federal Court on 17 May 1991]. PMID- 1935638 TI - [Syphilis]. PMID- 1935639 TI - [Prevention of associated gastropathy with non-steroidal antirheumatic agents]. PMID- 1935640 TI - [Traumatic carotid dissection after chiropractic therapy]. PMID- 1935641 TI - [Therapeutic control of hemorrhoidal bleeding using endoscopic Doppler sonography]. PMID- 1935642 TI - [Intracranial pressure in cerebral malaria]. PMID- 1935643 TI - [Percutaneous peripheral atherectomy in arterial occlusive disease. Angiographic and clinical acute and long-term results]. AB - 130 arteriosclerotic lesions--10 in the iliac, 109 in the superficial femoral, 10 in the popliteal and 1 in the anterior tibial artery--were treated by percutaneous atherectomy in 80 patients (62 men and 18 women: mean age 65 +/- 10 years). 23 of the lesions were concentric, 65 eccentric stenoses, while 42 were fully occlusive. 32 patients were in stage IIb (after Fontaine), 24 in stage IIa and 12 each in stage III or IV. Most of the stenoses were not suitable for conventional balloon dilatation because of their primary morphology. A good early angiographic result (residual stenosis less than 50%) was achieved in 94% of lesions. Mean stenosis degree was reduced from 85 +/- 12% to 12 +/- 10% (occlusions from 100% to 9 +/- 9%). The Doppler index increased from 0.6 +/- 0.18 to 0.85 +/- 0.15 (P less than 0.01). Follow-up angiography after 6 months in 104 lesions demonstrated an average stenosis degree of 33 +/- 25% (occlusions 44 +/- 28%). 26 of the 104 re-studied lesions fulfilled the criterion for re-stenosis (greater than 50%): six concentric ones and five eccentric ones, as well as 15 occlusions. These findings indicate that peripheral atherectomy can be employed with good short and long-term results even in morphologically unfavourable, markedly eccentric or calcified lesions and occlusions. PMID- 1935644 TI - [Lye corrosion of the esophagus. Course under long-term bougienage]. AB - In an alcoholic state a 61-year-old woman swallowed by mistake about 125 ml of a lye-containing glass-washing liquid (pH 12). About 30 min later she repeatedly brought up blood-containing vomitus and was admitted to hospital. Extensive corrosive damage in the oesophagus and entire stomach developed within a few days. Two weeks later a circular narrowing of the oesophageal lumen, which could not be passed endoscopically, was seen. Afterwards she repeatedly underwent endoscopic bougie dilatation. At the third dilatation the oesophagus was perforated, mediastinitis occurred but responded without further problems to conservative medical treatment. Two months after the initial injury a Billroth II gastric resection was performed because of complete stenosis of the gastric exit. Bougie dilatation was continued at widening intervals for 18 months after the ingestion. Subsequently the patient has remained without symptoms, although a secondary Barrett oesophagus has developed at the oesophago-gastric junction which, because of the potential danger of malignant degeneration, will require regular follow-up. PMID- 1935646 TI - [Microscopic examination of the urine. New detection using an old method]. PMID- 1935645 TI - [Cardiac metastasis as cause of therapy-resistant heart failure]. AB - Ultrasonography revealed a renal tumour (4 x 4 cm) in a 67-year-old man with right-sided lumbar pain and macrohematuria. In addition he had marked nocturnal dyspnoea with dry cough. He had lost about 10 kg in weight. On admission he had atrial fibrillation with an irregular ventricular rate (140 beats/min) and engorgement of the neck veins. Two-dimensional echocardiography, undertaken because of signs of increasing heart failure and a fall of systolic blood pressure to below 100 mm Hg, demonstrated a space-occupying lesion in the right ventricle, 4 x 2 x 1 cm, indicating an intracardiac thrombus or solid tumour. The heart failure continued to worsen, despite treatment with cardiac glycosides, verapamil and diuretics. Hence an exploratory thoracotomy was performed. This revealed an intracardiac tumour which had markedly displaced the right ventricular inflow tract and infiltrated the entire myocardium, but not the tricuspid valve. As much of the tumour as possible was resected, but the patient died postoperatively of heart failure. The intracardiac tumour proved to be a metastasis from the papillary carcinoma of the kidney. This had infiltrated the renal capsule and pelvis and invaded the branches of the right renal vein. PMID- 1935647 TI - [Risk of dysplasia and carcinoma in ulcerative colitis]. PMID- 1935648 TI - [Electric stimulation in fecal or urinary incontinence?]. PMID- 1935649 TI - [AIDS-associated non-Hodgkin's lymphoma]. PMID- 1935650 TI - [Hyperparathyroidism in alcoholic intoxication]. PMID- 1935651 TI - [Diagnostic value of ultrasonographic testing of the gallbladder function in cholelithiasis]. AB - Decrease in gall-bladder volume after intake of a test meal was assessed by ultrasound in 30 patients (24 females, 6 males; mean age 55 [22-82] years) with indications for elective or early elective cholecystectomy for cholelithiasis. Patients were assigned to three groups, based on intraoperative and histological gall-bladder changes: group 1 (n = 17), without changes or with mild chronic cholecystitis; group 2 (n = 4), with severe chronic inflammatory changes; group 3 (n = 9), with acute cholecystitis or cystic duct occlusion. A volume decrease of at least 30% after the test meal excluded only acute wall inflammation (negative predictive value 95.5%), while a volume reduction of at least 50% made it possible in a high percentage of cases (negative predictive value 88.2%) to predict correctly an absence of severe chronic wall changes. Before organ preserving treatment (extracorporeal lithotripsy or local litholysis) is undertaken, gall-bladder volume reduction of at least 50% should be documented. PMID- 1935652 TI - [Histiocytosis X. Clinical aspects and course in 5 patients]. AB - Histiocytosis X developed in five patients (one woman and four men) when aged between 15 and 44 years. The initial sign in four of them was eosinophilic granuloma of the bone, in one it was pulmonary involvement. In three patients the disease remained confined to bone, while in two it involved the lungs and central nervous system, respectively. Osteolysis regressed spontaneously in one of the men, while in the woman there has been no recurrence 8 years after resection of the focus. In another man an osteolytic focus in a rib was noted after a 9-year recurrence-free interval. The man with pulmonary and bone involvement received chemotherapy with vinblastine and prednisone: dyspnoea and cough disappeared, vital capacity improved and the interstitial lung changes regressed. The osteolytic foci were repeatedly irradiated in the man with bone and CNS involvement. This brought about considerable reduction in pain but no significant radiological changes of the foci. Two courses of chemotherapy were given over 12 years, once with vincristine and prednisone, afterwards with cyclophosphamide. This arrested the progression of the osteolytic foci, but each time they recurred when the drugs were stopped. PMID- 1935653 TI - [Type III hyperlipoproteinemia in monoclonal IgM gammopathy]. AB - A 42-year-old woman, found to have increased blood-lipid levels, developed hand line xanthomas 3 months later. She also had an increased erythrocyte sedimentation rate and a type lambda monoclonal IgM abnormality. In the course of the following 4 years the IgM concentration rose (from 5.8 to 12.3 g/l) steadily and synchronously with those of the triglycerides (from 147 to 391 mg/dl) and cholesterol (from 212 to 380 mg/dl). During the entire period of observation the ratio of VLDL cholesterol and triglyceride concentrations was elevated (greater than 0.4; normal: less than 0.3). Division of the lipoprotein fractions pointed to a type III hyperlipoproteinaemia. She also had an abnormality of lipid metabolism on the basis of a genetic defect (apolipoprotein-E2 homozygotism), which only manifested itself when an additional factor, IgM paraproteinaemia, was present. Paraproteins thus apparently interfered with the breakdown of the lipoproteins. Neither bezafibrate in increasing doses (200-800 mg daily) with low fat diet nor administration of lovastatin (20 mg twice daily) together with nicotinic acid (500 mg twice daily) were adequate treatment for this form of auto immune hyperlipidaemia. PMID- 1935654 TI - [Diagnosis of hyperthyroidism, hypothyroidism and goiter]. PMID- 1935655 TI - [Stable isotopes in diagnosis and research. New possibilities of noninvasive gastroenterology and metabolism research]. PMID- 1935656 TI - [Once more: collection of physicians' fees by accounting firms separate from the practice. Decision of the Federal Court of Justice, 7/10/1991]. PMID- 1935657 TI - [Thyroid diagnosis: false TSH determination caused by heterophilic antibodies]. PMID- 1935658 TI - [Doppler echocardiography in prosthetic heart valve replacement]. PMID- 1935659 TI - [Imipramine in sleep apnea syndrome]. PMID- 1935660 TI - [Insulin autoantibodies and islet cell antibodies in recently appearing diabetes mellitus type I. Association with age of manifestation and HLA phenotype]. AB - Insulin autoantibody (IAA) and islet cell antibody (ICA) titres were measured in 108 newly diagnosed type I diabetics (49 male, 59 female, mean age 20 [1-38] years) and 103 non-diabetic controls (41 male, 62 female, mean age 23 [16-46] years). IAA titres in the controls were normally distributed, with a mean of 5 +/ 11 nU/ml. The upper limit of normal was established as 49 nU/ml (mean + 4 standard deviations). Raised IAA and ICA titres were present in 45% and 44% of type I diabetics, respectively, with 59% positive for either IAA or ICA or both. IAA were markedly age-dependent, being positive in 70% (26 out of 37) of diabetics under the age of 15 years, and in 32% (23 out of 71) at the age of 15 years or more (P = 0.0004). There was a less marked difference for ICA titres (positive in 62% of patients less than 15 years, and in 35% of those of 15 years of older; P less than 0.01). IAA were significantly more common in HLA DR4 positive patients than in HLA DR4 negative patients (56% vs 11%; Pc less than 0.00015). With regard to age a significant association between IAA and HLA DR phenotype was present only in homozygous (Pc less than 0.03) and heterozygous (P less than 0.0003) patients aged 15 years or older. By contrast, ICA was not significantly correlated with HLA phenotype. These data suggest a genetic predisposition for the development of IAA. PMID- 1935661 TI - [Multilocular angiosarcoma with involvement of the heart]. AB - A thyroid tumour, initially diagnosed as an anaplastic carcinoma of the thyroid, was removed in a 66-year-old woman. Further examination, other than ultrasonography of the abdomen (normal), were refused, 26 months later a painful swelling was noted in the right buttock: a fist-sized haematoma, without evidence of malignancy was removed at another hospital. Computed tomography revealed a cystic tumour in the left upper abdomen, about 8 x 11 cm, not clearly related to any organ. Echocardiography, performed because of atrial fibrillation, demonstrated a space-occupying lesion, 42 x 38 mm, in the left atrium with central necroses and originating broad-based from the interatrial septum and the aortic root. The retroperitoneal upper-abdominal tumour encircling the root of the aorta and a gluteal tumour in the area of the previous haematoma could not be completely removed. Histologically they and the previously removed (and again examined) thyroid tumour were angiosarcomas. Removal of the atrial tumour was not attempted. Six months later it had penetrated the entire atrial septum and grown into the right atrium. The patient had lost 25 kg and three months later died of respiratory failure. Autopsy was refused. The findings suggest a left-atrial angiosarcoma which may well have been the primary tumour site. In case of angiosarcomatous tumours echocardiography should be performed as a staging examination. PMID- 1935662 TI - [Central anticholinergic intoxication syndrome. A contribution to the differential diagnosis of exogenous psychoses]. AB - A withdrawal syndrome in a 50-year-old alcoholic subsided within 5 days in response to treatment with doxepin (150 mg/d). But 2 days later he developed auditory hallucinations which were interpreted as alcohol hallucinations, for which he was additionally given haloperidol, 15 mg/d. He then developed early dyskinesia which was treated with 5 mg biperiden i.v. followed by twice 2 mg/d by mouth, while doxepin and haloperidol were continued. 5 days after detoxification there occurred, under this combination of drugs which included two with marked anticholinergic action, an anticholinergic intoxication syndrome characterized by restlessness, optical hallucinations, dysarthritic speech, mydriasis, urinary retention, fever, tachycardia and red, dry skin. After all previous drugs had been discontinued and clomethiazole started, the intoxication syndrome began to regress within 3 days. The case demonstrates the need to consider a central anticholinergic syndrome, which could end fatally, as a possible cause of otherwise unexplained delirium. PMID- 1935664 TI - [Therapy of hyperthyreosis, hypothyreosis and goiter]. PMID- 1935663 TI - [Anti-basal membrane glomerulonephritis after homologous kidney transplantation in hereditary Alport's nephropathy]. AB - A patient, born in 1968, was found at the age of 9 years to have Alport's syndrome. In his 20th year, when in terminal renal failure, his father's kidney was transplanted into him. 14 months later there was a sudden worsening of his renal function after a varicella infection; for the first time antibodies against the glomerular basal membrane (GBM) were detected. Despite an increase in prednisolone dosage and 6 plasmaphereses chronic haemodialysis again became necessary. Renal biopsy revealed necrotizing intra- and extracapillary glomerulonephritis. Simultaneously there was a raised anti-NC-1-antibody titre (1:80) in the serum. After removal of the transplant the titre fell to normal. The NC-1 antigen, a component of the GBM in healthy persons, may be absent in Alport's syndrome. An analysis of the few cases of anti-GBM glomerulonephritis in renal transplants of patients with Alport's syndrome may make it possible to recognize factors which precipitate or favour this form of glomerulonephritis. PMID- 1935665 TI - [Physical therapy and long-term oxygen therapy in diseases of the respiratory organs]. PMID- 1935666 TI - [Calcium antagonists in coronary heart disease?]. PMID- 1935667 TI - [Amalgam and Crohn disease]. PMID- 1935668 TI - [Resection of liver metastases of colorectal carcinoma]. PMID- 1935669 TI - [Icterus after a fall]. PMID- 1935670 TI - [Serotonin and acute ischemic heart disease]. PMID- 1935671 TI - [Sacroiliitis in familial Mediterranean fever]. AB - A 15-year-old girl of Turkish descent had for one year complained of severe recurrent fever-associated deep back pains. Since she was three years of age she had suffered from repeated attacks of fever and severe abdominal pain which ceased spontaneously in 1-3 days. On physical examination the sacrum and iliosacral joints were very painful to percussion, and she limped. Radiography revealed symmetric destructive sacroiliitis. Despite the unusual location of the arthritis, the triad of fever, abdominal pain and arthritis, as well as her belonging to an ethnic "at risk" group, pointed to the diagnosis of familial mediterranean fever (FML) or recurrent hereditary polyserositis. This diagnosis was confirmed by a positive metaraminol provocation test in that infusion of metaraminol reproduced the typical pains. Collagen diseases, rheumatic disease, acute porphyria and chronic infectious processes were excluded. The sacroiliitis quickly responded to long-term administration of colchicine, 0.5 mg twice daily. The patient also has Hageman factor deficiency whose significance remains unclear. PMID- 1935672 TI - [Anorexia/bulimia nervosa and mitral valve prolapse in a marathon runner]. AB - A 23-year-old male student (height 180 cm, weight 63 kg) without any cardiac symptoms underwent a cardiological examination and consultation before a marathon run. A holosystolic mitral valve prolapse was discovered. After the marathon run he developed anorexia nervosa, interrupted by brief bulimic periods, to a minimal weight of 48 kg. After psychosomatic in-patient treatment and a weight gain to 60 kg an anorexic period recurred and he lost weight. In this phase he had an iron deficiency anaemia (Hb 11.9 g/dl), leucopenia (2,900/microliters) and (compared with the status at the first examination) mild decrease in heart size, while the valve prolapse was unchanged. Ergometric capacity was still above normal, at 300 W. After taking iron, magnesium and potassium salts in-patient psychosomatic treatment was renewed. PMID- 1935673 TI - [The antiphospholipid syndrome. The neurological complications and the therapeutic possibilities]. AB - For several months a 23-year-old woman had been suffering from increasingly frequent attacks of bilateral amaurosis fugax. They affected only individual segments of a monocular visual field and finally occurred several times daily. Physical and cardiological examinations as well as echocardiography were within normal limits. Laboratory tests revealed a slight increase in erythrocyte sedimentation rate and high titres of serum antibodies against phospholipids. Fundoscopy did not show any vascular changes. Because vasculitis--possibly as an expression of systemic lupus erythematodes--was suspected, high-dosage treatment with steroids was commenced, but failed to influence the visual disorder. While steroid dosage was gradually decreased, administration of acetylsalicylic acid (for three months 100 mg daily, then three times daily 100 mg) brought about complete disappearance of the visual signs. Their cause was probably a reversible platelet aggregation induced by antiphospholipid antibodies which, because of the physiological characteristics of the terminal retinal vascular bed brought about the isolated sign of recurrent amaurosis fugax. PMID- 1935674 TI - [The therapy of rapidly progressing glomerulonephritis]. PMID- 1935675 TI - [Myocardial contrast echocardiography. Its clinical use for the analysis of heart muscle blood flow]. PMID- 1935676 TI - [The "heart cooler" in mud baths]. PMID- 1935677 TI - [The tuberculostearic acid study]. PMID- 1935678 TI - [The terminology and etymology of German anatomical technical terms for the stylo , zeugo-, basi- and metapodium of horses]. AB - The article reviews German anatomical terms applied to longer limb bones and their joints of the horse. The listed terms have been used in German veterinary and special veterinary anatomical hand- and textbooks since 1774; etymological remarks are made on some unusual words. PMID- 1935679 TI - [Microscopic studies of the skin of the Turkish angora goat. II. Functional morphology of the hair follicle]. AB - The study supplies a detailed description of the development, morphology and function of anagen hair follicles in the Turkish Angora goat. In this connection, the formation of the hair root and the epithelial root sheaths is of specific interest. Furthermore, the intensive structural alterations and disintegrative processes occurring during the catagen phase are presented. The telogen hair follicle development is also referred to with special regard to typical structural and functional features. PMID- 1935680 TI - Metabolic behaviour and tissue distribution of nalidixic acid in chickens. AB - The metabolic behaviour and tissue distribution of nalidixic acid in normal and E. coli infected chickens were carried out using spectrofluorimetric and microbiological techniques following a single and multiple oral administration of 25 mg/kg b. wt. The obtained results revealed that free nalidixic acid (free NA) is the major fraction of the total drug concentration in serum, liver and kidneys. The free active nalidixic acid was in a higher concentration than hydroxynalidixic acid (free HNA) and both conjugates of NA and HNA following single and multiple oral administration. The obtained results showed that nalidixic acid was highly distributed in all tissues in normal and E. coli infected chickens, with the highest concentrations in kidneys, liver and heart and lowest concentrations in brain, muscles and intestine following oral administration of 25 mg/kg b. wt. twice daily for 5 successive days. Spectrofluorimetic technique was more sensitive for nalidixic acid determination than microbiological method. Nalidixic acid revealed longer withdrawal time in diseased chickens than in normal chickens. PMID- 1935681 TI - [Effect of equilateral administration of monensin and tiamulin on the peripheral nerve function and the electrocardiogram of broilers]. AB - The influence of the simultaneous administration of monensin and tiamulin on the motor nerve conduction velocity and the refractory periods of the N. ischiadicus was studied on 4-week old cockerels. The combined administration of the two substances resulted in significant decrease of the conduction velocities of the peripheral nerve, while the relative and absolute refractory periods were seen to increase significantly as a result of the medications. The observed alteration of the peripheral nerve function in the early phase can already attribute to the development of the serious clinical signs of the toxic interaction. The simultaneous application of monensin and tiamulin caused also changes in the electrocardiogram which was expressed in a prolongation of the RS interval and the ST segment. At the same time the heart rate was reduced. PMID- 1935682 TI - [Detection of neutralizing antibodies against Pasteurella multocida toxin in swine with atrophic rhinitis]. AB - Blood sera of 1171 pigs, not vaccinated against PAR, were tested for antibodies against P. multocida toxin in a neutralization test with EBL cell cultures. 277 sera were from 18 herds with clinical PAR; 104 of them (37.5%) had neutralizing antibody titres from 1:2 to 1:1024. No antitoxin was detected in the sera of 866 pigs in 25 PAR nonsuspicious herds. In one nonsuspicious herd, however, 11 of 28 sera were neutralizing in the 1:2 or 1:4 dilution. 30 sows had been vaccinated with inactivated toxigenic P. multocida and/or with the P. multocida toxoid. 21 of these sows had neutralizing sera with titres between 1:8 and 1:4096. The neutralization test presented can be applied for herd diagnosis of PAR and for demonstration of vaccination effects. PMID- 1935683 TI - [Intensive culture of fresh water fish]. AB - Recently, eel recirculation systems have provoked increasing attention in intensive fish culture, especially concerning animal welfare. "Aquaculture", "Intensive Culture", and "Recirculation Systems" are often confused with each other. This study, first of all, differentiates among these terms. The economic relevance of aquaculture in the Federal Republic of Germany is demonstrated by figures. A tendency towards intensive methods can only be seen in trout and eel culture. The problems of recirculation systems are explained comprehensively. Particular emphasis is laid on the conflict between theoretical suitability of intensive fish production and the absence of commercially working systems. At present, intensive fish culture does not pose a serious animal welfare problem in Germany. However, it is necessary to define the biological requirements of fish concerning their optimal accommodation in aquaculture facilities. According to the Law for the Protection of Animals, these requirements have to be laid down in an ordinance. Only then control is possible as to whether aquaculture systems fulfill fish welfare demands. PMID- 1935684 TI - The maternal gene nanos has a central role in posterior pattern formation of the Drosophila embryo. AB - A group of maternal genes, the posterior group, is required for the development of the abdominal region in the Drosophila embryo. We have used genetic as well as cytoplasmic transfer experiments to order seven of the posterior group genes (nanos, pumilio, oskar, valois, vasa, staufen and tudor) into a functional pathway. An activity present in the posterior pole plasm of wild-type embryos can restore normal abdominal development in posterior group mutants. This activity is synthesized during oogenesis and the gene nanos most likely encodes this activity. The other posterior group genes have distinct accessory functions: pumilio acts downstream of nanos and is required for the distribution or stability of the nanos-dependent activity in the embryo. Staufen, oskar, vasa, valois and tudor act upstream of nanos. Embryos from females mutant for these genes lack the specialized posterior pole plasm and consequently fail to form germ-cell precursors. We suggest that the products of these genes provide the physical structure necessary for the localization of nanos-dependent activity and of germ line determinants. PMID- 1935685 TI - Aldehyde dehydrogenase is a positional marker in the retina. AB - An asymmetrically distributed protein in the embryonic mouse retina was identified as an aldehyde dehydrogenase through protein microsequencing. It was characterized as a cytosolic isoform with basic isoelectric point and preference for aliphatic substrates, features that resemble those of the isoform AHD-2 which is known to oxidize retinaldehyde to retinoic acid. Immunohistochemistry with aldehyde dehydrogenase antisera showed strong labeling of the dorsal retina from the early eye vesicle stage into adulthood. In addition, optic axons originating from the dorsal retina were transiently labeled during their outgrowth phase. Whereas in the embryo the enzyme was expressed in undifferentiated cells and in neurons, in the retina of the adult mouse the asymmetrically distributed isoform was mainly expressed in Muller glia, with the number of labeled glial cells varying with retinal position. PMID- 1935686 TI - Specification of neurepithelium and surface epithelium in avian transplantation chimeras. AB - Previous studies of the avian blastoderm have revealed that extensive displacements occur within the epiblast during gastrulation and neurulation. The present study had two main purposes: (1) to map the origin and movement of prospective surface epithelial cells, and (2) to ask whether neurepithelial and surface epithelial cell fates are determined prior to cell movement, or whether they arise later as a result of the ultimate position attained by cells through their movement. Our results show that the rostral and lateral intraembryonic and extraembryonic surface epithelium originates as far laterally as at the area pellucida-area opaca interface of the early epiblast. Intraembryonic surface epithelial cells rearrange relative to one another, extending medially to contribute to the formation of the neural folds, whereas extraembryonic surface epithelial cells maintain their lateral positions, spreading uniformly as the epiblast expands. Our results further show that surface epithelial and neurepithelial cell fates are labile at the onset of neurulation, suggesting that cell fate is specified following cell movement. PMID- 1935687 TI - Stereotyped pathway selection by growth cones of early epiphysial neurons in the embryonic zebrafish. AB - In this report we have examined the development of one of the earliest projections in the embryonic zebrafish brain, that from the epiphysis. Epiphysial axons and growth cones were labelled anterogradely in whole-mounted brains, using either the carbocyanine dye, diI, or horseradish peroxidase (HRP). Some embryos were also either stained with anti-acetylated tubulin or HNK-1 antibodies to reveal other axons in the brain, or were secondarily sectioned for light and electron microscopy. The epiphysial axons have a very specific projection pattern and virtually all axons grow precisely to their target regions without error. The first epiphysial growth cone extends ventrally from the epiphysis into the dorsoventral diencephalic tract at 19-20 h post-fertilisation (h PF). Several hours later, it turns rostrally to grow alongside axons in the tract of the postoptic commissure. The morphology of the leading growth cone changes in predictable ways at different locations along its pathway and these changes correlate with differences in the local environment that it encounters. In contrast to other published descriptions of other developing systems, the epiphysial growth cone is no more complex either when pioneering a pathway, or when encountering divergent axonal pathways. Indeed, it is most complex (i.e. has the greatest number of processes) when it first starts to follow the tract of the postoptic commissure. The presence and selective retention of filopodia within other axonal pathways suggests that growth cones have access to these pathways but do not select them. These observations support the notion that local guidance cues exist within the early scaffold of brain tracts. Subsequent epiphysial axons form a tight fascicle within the dorsoventral diencephalic tract, but abruptly defasciculate from each other upon turning rostrally into the tract of the postoptic commissure. Epiphysial growth cones that enter this tract at abnormal locations still turn in the appropriate direction. Therefore, guidance cues are not restricted solely to the normal intersections but may be distributed along the length of the tracts. The epiphysial growth cones and axons have very characteristic spatial relations to other axons in the tracts of the developing brain. They are restricted to the dorsal region of the tract of the postoptic commissure and the rostral region of the postoptic commissure. At early developmental stages, the epiphysial axons are the only axons within the dorsoventral diencephalic tract and they are located very superficially within the neuroepithelium. At later stages, they are displaced to deeper regions of the neuropil by non-epiphysial axons. PMID- 1935688 TI - The embryonic origin of imaginal discs in Drosophila. AB - The thoracic imaginal discs of Drosophila melanogaster can be observed during embryogenesis as clusters of cells with particular shapes, sizes and behaviours. These structures can be detected soon after germ band shortening and their development appears to be tightly linked to that of the larval epidermis. PMID- 1935689 TI - Gastrulation in Drosophila: the formation of the ventral furrow and posterior midgut invaginations. AB - The ventral furrow and posterior midgut invaginations bring mesodermal and endodermal precursor cells into the interior of the Drosophila embryo during gastrulation. Both invaginations proceed through a similar sequence of rapid cell shape changes, which include apical flattening, constriction of the apical diameter, cell elongation and subsequent shortening. Based on the time course of apical constriction in the ventral furrow and posterior midgut, we identify two phases in this process: first, a slow stochastic phase in which some individual cells begin to constrict and, second, a rapid phase in which the remaining unconstricted cells constrict. Mutations in the concertina or folded gastrulation genes appear to block the transition to the second phase in both the ventral furrow and the posterior midgut invaginations. PMID- 1935690 TI - A regulatory region from the mouse Hox-2.2 promoter directs gene expression into developing limbs. AB - To characterize cis-acting regulatory elements of the murine homeobox gene, Hox 2.2, transgenic mouse lines were generated that contained the LacZ reporter gene under the control of different fragments from the presumptive Hox-2.2 promoter. A promoter region of 3600 base pairs (bp) was identified, which reproducibly directed reporter gene expression into specific regions of developing mouse embryos. At 8.5 days postcoitum (p.c.) reporter gene activity was detected in posterior regions of the lateral mesoderm and, in subsequent developmental stages, expression of the LacZ gene was restricted to specific regions of the developing limb buds and the mesenchyme of the ventrolateral body region. This pattern of Hox-2.2-LacZ expression was found in all transgenic embryos that have been generated with the 3.6 kb promoter fragment (two founder embryos and embryos from five transgenic lines). In addition, embryos from two transgenic mouse lines expressed the reporter gene at low levels in the developing central nervous system (CNS). Our results are consistent with the idea that in addition to their presumptive role in CNS and vertebrae development, Hox-2.2 gene products are involved in controlling pattern formation in developing limbs. PMID- 1935691 TI - Substitution for mesenchyme by basement-membrane-like substratum and epidermal growth factor in inducing branching morphogenesis of mouse salivary epithelium. AB - Mouse salivary epithelium cannot undergo branching morphogenesis in the absence of the surrounding mesenchyme. To clarify the nature of the mesenchymal influence on the epithelium, we have investigated the culture conditions in which the epithelium could normally branch in the absence of mesenchymal cells. Combination of basement-membrane-like substratum (Matrigel) and epidermal growth factor (EGF) could substitute for the mesenchyme, the epithelium showing typical branching morphogenesis. Transforming growth factor alpha had the same effect as EGF. Matrigel plus basic fibroblast growth factor or transforming growth factor beta 1 and collagen gel plus EGF were not sufficient to support the branching of the epithelium. These results clearly reveal that the role of mesenchyme in salivary morphogenesis is both to provide the epithelium with an appropriate substratum and to accelerate growth of the epithelium. PMID- 1935692 TI - Autonomy and nonautonomy of sex determination in triploid intersex mosaics of C. elegans. AB - The primary sex-determining signal in Caenorhabditis elegans is the ratio of X chromosomes to sets of autosomes (X/A ratio), normally 1.0 in hermaphrodites (XX) and 0.5 in males (XO). XX triploids (X/A = 0.67) are males, but if these animals carry a partial duplication of the X chromosome such that X/A approximately equal to 0.7, they develop as intersexes that are sexually mosaic. We have analyzed these mosaics using Nomarski microscopy and in situ hybridization to obtain information on whether sex determination decisions can be made independently in different cells and tissues, and when these commitments are made. The observed patterns of male and female cells in individual animals indicate that sex determination decisions can be influenced by anterior-posterior position and that sex determination decisions can be made as late as the third larval stage of postembryonic development. Although these decisions clearly can be made independently in different lineages, they show substantial biases toward one sex or the other in individual animals. We interpret these results to suggest that sex determination in C. elegans is not entirely cell autonomous. PMID- 1935693 TI - Interactions of different vegetal cells with mesomeres during early stages of sea urchin development. AB - It has been known from results obtained in the classical experiments on sea urchin embryos that cell isolation and transplantation showed extensive interactions between the early blastomeres and/or their descendants. In the experiments reported here a systematic reexamination of recombination of mesomeres and their progeny (which come from the animal hemisphere) with various vegetal cells derived from blastomeres of the 32- and 64-cell stage was carried out. Cells were marked with lineage tracers to follow which cell gave rise to what structures, and newly available molecular markers have been used to analyze different structures characteristic of regional differentiation. Large micromeres form spicules and induce gut and pigment cells in mesomeres, conforming to previous results. Small micromeres, a cell type not heretofore examined, gave rise to no recognizable structure and had very limited ability to evoke poorly differentiated gut tissue in mesomeres. Macromeres and their descendants, Veg 1 and Veg 2, form primarily what their normal fate dictated, though both did have some capacity to form spicules, presumably by formation from secondary mesenchyme. Macromeres and their descendants were not potent inducers of vegetal structures in animal cells, but they suppress the latent ability of mesomeres to form vegetal structures. The results lead us to propose that the significant interactions during normal development may be principally suppressive effects of mesomeres on one another and of adjacent vegetal cells on mesomeres. PMID- 1935694 TI - Functional tagging of regulatory elements in the plant genome. AB - In comparison with animals, relatively few plant genes have been identified that have been shown to be under organ-, tissue- or cell-type-specific regulation. In this paper, we describe how the beta-glucuronidase (GUS) reporter gene (gusA or uidA), fused to a weak promoter (a truncated (-90 bp) CaMV35S promoter), can be used to identify tissue-specific markers in transgenic tobacco plants. The rationale was that the expression of gusA would be determined primarily by position effect. Quantitative analysis revealed that, of 184 -90-gus transgenic plants, 73% exhibited gusA gene activation in leaf tissue, and the level of GUS enzyme activity varied over a 300-fold range within the population. In comparison, transformation with a promoterless gusA gene resulted in GUS expression in 78% of all plants analyzed (in leaf and/or root) and expression levels were three-fold or more lower. Qualitative GUS analysis of single locus 90-gus transformants revealed differential expression in diverse tissues. The spatial pattern of GUS activity was unique to individual transformants, was a reflection of differential gusA gene transcription, and was stably transmissible to progeny. Evidence for preferential expression in roots not only of the -90 gus, but also the promoterless gusA gene is presented. The value of the -90 bp promoter-gusA sequence, which is termed an 'interposon', as a tool both to identify native enhancer sequences in situ and to investigate position effects in plants, is discussed. PMID- 1935695 TI - The switch from larval to adult globin gene expression in Xenopus laevis is mediated by erythroid cells from distinct compartments. AB - The transition of hemoglobins during metamorphosis of Xenopus laevis involves replacement of the larval erythrocytes by adult ones, suggesting that the developmental control of this event depends upon the growth characteristics of the precursor cells. To identify the erythroid precursor cells and to investigate their developmental fate, we analyzed the distribution of stage-specific globin mRNAs by northern blotting in dorsal and ventral fragments of stage 32 embryos after in vitro culture as well as presumptive erythropoietic tissues of tadpoles during metamorphosis. The histological analysis shows that erythrocytes differentiate only in ventral fragments, suggesting that the ventral blood islands and most likely also the dorsolateral mesoderm are the primary sites of erythropoiesis. We also demonstrate that the first generations of erythrocytes, already express the predominating larval-specific alpha-globin mRNAs. The globin mRNA patterns obtained from presumptive erythropoietic tissues suggest an important role of circulating precursor cells in larval erythropoiesis, whereas the liver appears to be the main site of formation and maturation of the adult erythrocytes. Tentatively we propose that anuran erythropoiesis is dependent upon a self-perpetuating stem-cell line and that the larval and the adult erythrocytes are derived from successive generations of erythroid precursors, whose commitment may be imposed by the erythropoietic sites. PMID- 1935696 TI - Developmental expression of rat cardiac troponin I mRNA. AB - We have isolated and sequenced a full-length cDNA clone of rat cardiac troponin I (TnI). The amino acid sequence of rat cardiac TnI is highly similar to that of other mammalian species in the portion of the molecule (residues 33-210) that is also homologous to skeletal muscle TnI isoforms. In contrast, a lower degree of similarity is present in the cardiac TnI-specific amino terminal extension (residues 1-32). This region contains a conserved serine residue that has been shown to be selectively phosphorylated by cAMP-dependent protein kinase. Cardiac TnI mRNA is weakly expressed in the 18-day fetal heart and accumulates in neonatal and postnatal stages. No difference can be demonstrated between TnI mRNAs present in fetal and postnatal heart by RNAase protection assays. The fetal and neonatal, but not the adult heart, contain significant amounts of slow skeletal TnI transcripts, detected by oligonucleotide probes specific for the 5'- and 3'-untranslated regions of slow skeletal TnI mRNA. In situ hybridization studies show that cardiac and slow skeletal TnI mRNAs are coexpressed in the rat heart from embryonic day 11 throughout fetal and perinatal stages. Changes in troponin isoform expression during development may be responsible for the difference in calcium sensitivity and in the response to beta-adrenergic stimulation between fetal and adult heart. PMID- 1935697 TI - The development of the sensory neuron pattern in the antennal disc of wild-type and mutant (lz3, ssa) Drosophila melanogaster. AB - The development of the sensory neuron pattern in the antennal disc of Drosophila melanogaster was studied with a neuron-specific monoclonal antibody (22C10). In the wild type, the earliest neurons become visible 3 h after pupariation, much later than in other imaginal discs. They lie in the center of the disc and correspond to the neurons of the adult aristal sensillum. Their axons join the larval antennal nerve and seem to establish the first connection towards the brain. Later on, three clusters of neurons appear in the periphery of the disc. Two of them most likely give rise to the Johnston's organ in the second antennal segment. Neurons of the olfactory third antennal segment are formed only after eversion of the antennal disc (clusters t1-t3). The adult pattern of antennal neurons is established at about 27% of metamorphosis. In the mutant lozenge3 (lz3), which lacks basiconic antennal sensilla, cluster t3 fails to develop. This indicates that, in the wild type, a homogeneous group of basiconic sensilla is formed by cluster t3. The possible role of the lozenge gene in sensillar determination is discussed. The homeotic mutant spineless-aristapedia (ssa) transforms the arista into a leg-like tarsus. Unlike leg discs, neurons are missing in the larval antennal disc of ssa. However, the first neurons differentiate earlier than in normal antennal discs. Despite these changes, the pattern of afferents in the ectopic tarsus appears leg specific, whereas in the non-transformed antennal segments a normal antennal pattern is formed. This suggests that neither larval leg neurons nor early aristal neurons are essential for the outgrowth of subsequent afferents. PMID- 1935698 TI - Well-defined growth factors promote cardiac development in axolotl mesodermal explants. AB - The effect of growth factors on the formation of cardiac mesoderm in the urodele, Ambystoma mexicanum (axolotl), has been examined using an in vitro explant system. It has previously been shown that cardiac mesoderm is induced by pharyngeal endoderm during neurula stages in urodeles. In this study, explants of prospective cardiac mesoderm from early neurula stage embryos rarely formed beating cardiac tissue in culture. When transforming growth factor beta-1 (TGF beta 1) or platelet-derived growth factor BB (PDGF) was added to such explants, the frequency of heart tissue formation increased markedly. The addition of other growth factors to these explants did not enhance cardiac mesoderm formation. The addition of basic fibroblast growth factor (bFGF) to prospective heart mesoderm derived from later stage embryos resulted in a decreased tendency to form cardiac tissue. These results suggest that growth factors analogous to TGF-beta 1, PDGF, and bFGF may regulate the initial stages of vertebrate cardiac development in vivo. PMID- 1935699 TI - Autonomous differentiation of dorsal axial structures from an animal cap cleavage stage blastomere in Xenopus. AB - Dorsal or ventral blastomeres of the 16- and 32-cell stage animal hemisphere were labeled with a lineage dye and transplanted into the position of a ventral, vegetal midline blastomere. The donor blastomeres normally give rise to substantial amounts of head structures and central nervous system, whereas the blastomere which they replaced normally gives rise to trunk mesoderm and endoderm. The clones derived from the transplanted ventral blastomeres were found in tissues appropriate for their new position, whereas those derived from the transplanted dorsal blastomeres were found in tissues appropriate for their original position. The transplanted dorsal clones usually migrated into the host's primary axis (D1.1, 92%; D1.1.1, 69%; D1.1.2, 100%), and in many cases they also induced and populated a secondary axis (D1.1, 43%; D1.1.1, 67%; D1.1.2, 63%). Bilateral deletion of the dorsal blastomeres resulted in partial deficits of dorsal axial structures in the majority of cases, whereas deletions of ventral midline blastomeres did not. When the dorsal blastomeres were cultured as explants they elongated. Notochord and cement glands frequently differentiated in these explants. These studies show that the progeny of the dorsal, midline, animal blastomeres: (1) follow their normal lineage program to populate dorsal axial structures after the blastomere is transplanted to the opposite pole of the embryo; (2) induce and contribute to a secondary axis from their transplanted position in many embryos; (3) are important for the normal formation of the entire length of the dorsal axis; and (4) autonomously differentiate in the absence of exogenous growth factor signals. These data indicate that by the 16 cell stage, these blastomeres have received instructions regarding their fate, and they are intrinsically capable of carrying out some of their developmental program. PMID- 1935700 TI - Migrating neural crest cells in the trunk of the avian embryo are multipotent. AB - Trunk neural crest cells migrate extensively and give rise to diverse cell types, including cells of the sensory and autonomic nervous systems. Previously, we demonstrated that many premigratory trunk neural crest cells give rise to descendants with distinct phenotypes in multiple neural crest derivatives. The results are consistent with the idea that neural crest cells are multipotent prior to their emigration from the neural tube and become restricted in phenotype after leaving the neural tube either during their migration or at their sites of localization. Here, we test the developmental potential of migrating trunk neural crest cells by microinjecting a vital dye, lysinated rhodamine dextran (LRD), into individual cells as they migrate through the somite. By two days after injection, the LRD-labelled clones contained from 2 to 67 cells, which were distributed unilaterally in all embryos. Most clones were confined to a single segment, though a few contributed to sympathetic ganglia over two segments. A majority of the clones gave rise to cells in multiple neural crest derivatives. Individual migrating neural crest cells gave rise to both sensory and sympathetic neurons (neurofilament-positive), as well as cells with the morphological characteristics of Schwann cells, and other non-neuronal cells (both neurofilament-negative). Even those clones contributing to only one neural crest derivative often contained both neurofilament-positive and neurofilament-negative cells. Our data demonstrate that migrating trunk neural crest cells can be multipotent, giving rise to cells in multiple neural crest derivatives, and contributing to both neuronal and non-neuronal elements within a given derivative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1935701 TI - Quantitative analysis of protein synthesis in mouse embryos. I. Extensive reprogramming at the one- and two-cell stages. AB - A quantitative, high-resolution, two-dimensional gel protein database has been constructed for the mouse embryo. This database has been used to obtain a detailed accounting of the amount and relative timing of changes in protein synthesis that occur during the 1-, 2-, and 4-cell stages along with a description of the most prevalent developmentally regulated patterns of synthesis. We find that during these early stages of development the pattern of proteins synthesized changes to a much greater extent than previously appreciated. During the 1- and 2-cell stages, the majority (60% and 85%, respectively) of the analyzed proteins exhibit twofold or greater changes in their rates of synthesis. The periods of greatest change are the late 1-cell and mid 2-cell stages, during which an extensive remodelling of protein synthetic pattern occurs that is largely complete by 15 h following the first cleavage. Once this reprogramming is complete, very little change is observed during the late 2-cell and 4-cell stages. Cluster analysis of individual protein synthesis patterns reveals a limited number of coordinately regulated protein sets that are responsible for most of the changes observed during the 1- and 2-cell stages. During the 2-cell stage, one third of the proteins increase by an average of fivefold, another third decrease by an average of sevenfold, and 10% undergo transient changes in rates of synthesis. These patterns reflect the switch from zygotic to maternal mRNA utilization following transcriptional activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1935702 TI - Developmental and regional expression of thyroid hormone receptor genes during Xenopus metamorphosis. AB - A characteristic feature of the obligatory control of amphibian metamorphosis by thyroid hormones is the early acquisition of response of tadpole tissues to these hormones well before the latter are secreted, with 'exponentially' increasing hormonal sensitivity upon the onset of metamorphosis. We have therefore analyzed the expression of the two thyroid hormone receptor genes (TR alpha and beta) before, during and after metamorphosis in Xenopus tadpoles and froglets. Using non-cross-hybridizing cRNA probes for 5' and 3' sequences of Xenopus TR alpha and beta transcripts for RNAase protection assays, the two mRNAs can be detected in tadpoles as early as stage 39. Their concentration increases abruptly at stage 44 and continues to increase differentially at the onset of metamorphosis (stage 55) and through metamorphic climax at stages 58-62, after which they decline upon completion of metamorphosis at stage 66. Quantitative densitometric scanning of autoradiograms showed that, although the concentration of TR beta transcripts is about 1/30th of that of TR alpha mRNA at stages 44-48, depending on the region, it accumulates 3-10 times more rapidly than does the alpha isoform during further development. A substantial proportion of the increase in TR beta mRNA is localized to the head region of tadpoles. Using the hormone-binding domain (HBD) and 3' end of Xenopus TR alpha cRNA as probe for in situ hybridization, the highest concentration of TR transcripts in stage 44 tadpoles is seen in the brain and spinal cord. High concentrations of mRNA are also present in the intestinal epithelium and tail tip, tissues programmed for regression. At later stages (55 onwards), strong hybridization signals are also exhibited by hindlimb buds. This pattern persists through metamorphic climax, after which TR mRNAs decline in all tissues to low levels in froglets at stage 66. In developing froglets, TR transcripts were detected in large amounts in the cytoplasm of stage 1 and 2 oocytes but the rate of their accumulation did not increase with further oocyte growth. This observation raises the possibility that the response to thyroid hormones at early stages of tadpoles (42-44) may be due to TR synthesized on maternally derived mRNA. Exposure of tadpoles at premetamorphic stages (48-52) to exogenous thyroid hormone (T3) substantially enhanced the accumulation of TR mRNA, especially that of TR beta message, which could explain the accelerated increase in sensitivity of tadpoles to thyroid hormones at the onset of natural metamorphosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935703 TI - The regulation of the cell cycle during Drosophila embryogenesis: the transition to polyteny. AB - The process of polytenization plays a crucial role in Drosophila development, and most of the larval tissues are polytene. By analyzing the pattern of DNA replication in embryos pulse-labeled with BrdU, we show that many larval tissues undergo a transition to begin becoming polytene late in embryogenesis. Our results demonstrate that in these larval tissues polyteny results from a modified cell cycle, the endo cell cycle, in which there is only an S (synthesis) phase and a G (gap) phase. A key regulator of the mitotic cell cycle, the product of the string gene (the Drosophila homologue of cdc25), is not required for the endo cell cycle. The developmental regulation of the endo cell cycle is striking in that tissue-specific domains undergo polytene DNA replication in a dynamic pattern at defined times in embryogenesis. During subsequent rounds of the endo cell cycle in late embryogenesis and first instar larval development, the domains are subdivided and the temporal control is not as rigid. The length of the G phase varies among different tissues. By quantifying DNA content, we show that during the early polytene S phases the genome is not fully duplicated. PMID- 1935704 TI - Contact hypersensitivity response to o-benzyl-p-chlorophenol in mice. AB - o-Benzyl-p-chlorophenol was evaluated for its potential as a sensitizing agent for allergic contact hypersensitivity in mice. Female B6C3F1 mice were sensitized with 1.0, 3.0, and 10.0% o-benzyl-p-chlorophenol and challenged with 20.0% o benzyl-p-chlorophenol. Doses of o-benzyl-p-chlorophenol were selected from assays for primary irritancy. Mice received 20 microliters by direct dermal application, for 5 days, to sites prepared by shaving, dermabrading and, in some mice, with intra dermal injection of Freund's complete adjuvant. The rest period was 7 days. Measurement of the contact hypersensitivity response in mice was by radioisotopic assay two days after challenge and mouse ear swelling test one and two days after challenge. Mice demonstrated statistically significant dose-dependent contact hypersensitivity response to o-benzyl-p-chlorophenol with or without adjuvant pretreatment. PMID- 1935705 TI - Acute inhalation toxicity studies in several animal species of an ethylene oxide/propylene oxide copolymer (UCON 50-HB-5100). AB - An acute inhalation toxicity study in several species of animals with an ethylene oxide/propylene oxide copolymer (EO/PO) having a molecular weight of 4000 [UCON 50-HB-5100, CAS #9038-95-3] was designed to determine if any species variation could be shown. Species tested included: rats, mice, hamsters, guinea pigs, and dogs. The test material was administered as a respirable liquid aerosol for 4 hours at target concentrations of 50, 100, 200, and 500 mg/m3. A vehicle control group was exposed to a distilled water aerosol. The 4 hours LC50's were calculated to be 147 mg/m3 [rats], 174 mg/m3 [mice], 293 mg/m3 [guinea pigs] and 511 mg/m [hamsters]. The dog LC50 was determined to be greater than 500 mg/m3 since all the test animals survived exposure to this concentration. These values show that rats and mice were the most sensitive species with a declining response in guinea pigs, hamsters and dogs. Lung weights were increased at all exposure concentrations in rats, mice and hamsters. Lung weights were increased in guinea pigs at exposure concentrations of 100 mg/m3 and above. Lung weights in dogs were increased only at the 500 mg/m3 exposure concentration. Significant pathological changes were limited to the lungs and were more common in animals which died prior to scheduled sacrifice. Grossly, these lung changes consisted of red discoloration, edema, emphysema, and surface irregularities. Microscopic findings in the lungs included acute congestion and hemorrhage and, less commonly, acute interstitial inflammation. PMID- 1935706 TI - Physostigmine (alone and together with adjunct) pretreatment against soman, sarin, tabun and VX intoxication. AB - A pretreatment for organophosphorus (OP) anticholinesterase (e.g., soman) intoxication should prevent lethality and convulsions (CNV) at 2 LD50s and be behavioral-decrement-free when given alone. Behavioral-deficit-free pretreatment regimens (PRGs) for guinea pigs consisted of Physostigmine (0.15 mg/kg, im) and adjunct. Adjuncts [mg/kg, im] tested were akineton [0.25], aprophen [8], trihexyphenidyl [2], atropine [16], azaprophen [5], benactyzine [1.25], cogentin [4], dextromethorphan [7.5], ethopropazine [12], kemadrin [1], memantine [5], promethazine [5], scopolamine [0.08] and vontrol [2]. PRGs were given 30 min before soman (60 micrograms/kg, sc; 2 LD50s) or other OP agents. Animals were then observed and graded for signs of intoxication, including CNV at 7 time points and at 24 hr. Physostigmine alone reduced the incidence of CNV and lethality induced by 2 LD50s of soman by 42 and 60%, respectively. All of the PRGs tested abolished lethality and 12 shortened recovery time to 2 hr or less. Also, PRGs including azaprophen or atropine prevented CNV. When selected PRGs were tested against intoxication by sarin, tabun or VX, the efficacy was generally superior to that for soman. The data show that several PRGs are effective against soman intoxication in guinea pigs. PMID- 1935707 TI - Actions and interactions of cholinolytics and cholinesterase reactivators in the treatment of acute organophosphorus toxicity. AB - Different drug combinations consisting of cholinolytic and a cholinesterase (ChE) reactivator provide greater therapeutic efficacy in acute organophosphorus (OP) poisoning in mice than when used alone. Maximum protection, as determined by a shift of the LD50 for the two OP agents, was observed with the cholinolytic benactyzine. A protection index (P.I.) of 42 was obtained when benactyzine was given along with obidoxime in diisopropylphosphorofluoridate (DFP) intoxication. With the more toxic OP agent soman (o-pinacolylmethylphosphonofluoridate), the same cholinolytic only offered a maximum P.I. of 3.2 when administered with HS-6, another bispyridinium ChE reactivator. This beneficial effect of benactyzine is possibly due to its greater antimuscarinic effect in the central nervous system than atropine or dexetimide. PMID- 1935708 TI - Effect of subacute administration of isoniazid and pyridoxine on lipids in plasma, liver and adipose tissues in the rabbit. AB - The effect of subacute intraperitoneal administration of Isoniazid (INH) on various lipid parameters was studied in liver and adipose tissue in addition to plasma. In the liver, its effect on various phospholipid fractions was also assessed. The changes in lipid profile reflected INH-induced hepatic steatosis. While pyridoxine alone did not alter any of these lipid parameters, its concurrent administration with INH prevented almost all the INH-induced lipid changes. The enhanced lipid mobilization into liver, and a fall in phosphatidylcholine with a concomitant rise in phosphatidylethanolamine in liver impeding lipoprotein synthesis, might be responsible for the hepatic steatosis. Pyridoxal, a pyridoxine metabolite, might have trapped the primary amine functional group of acetylhydrazine and thus prevented the steatosis. PMID- 1935709 TI - Cardiotoxicity and hypertension in rats after oral lead exposure. AB - The rats were exposed to lead (0.25, 0.5 and 1.0 per cent lead acetate through drinking water) for 90 days to study its effect on some physiological and morphological parameters of the cardiovascular system. Blood lead levels increased in a dose dependent manner but heart tissue showed rise at only two higher doses in exposed animals. The two higher doses of lead resulted in an increased arterial blood pressure and calcium influx in atrial trabeculae and papillary muscles. No marked pathological or histochemical changes were observed in heart tissue excepting congestion and slightly reduced activity of succinic dehydrogenase in the highest dosed group. It was concluded that lead exposure through drinking water may produce increased arterial blood pressure and minor changes in the myocardium. Whether these changes are mediated through the effect of lead on the calcium transport needs further investigation. PMID- 1935710 TI - Incidence and treatment of deviation of nasal septum in newborns. AB - Four thousand and ninety consecutive newborns were investigated for nasal septal deviations over a two-year period in the Bnai Zion Medical Center, Haifa. An incidence of 0.93% of anterior nasal septal cartilaginous dislocation was found. No statistically significant correlation was observed between the newborns' weight and the nasal deformities. Definite correlation between the type of delivery and the nasal deformity was noted, however. The importance of early treatment during the first three days after birth is stressed. The infants were followed for a three-year period and no evidence of recurring septal deformity was noted. Birth trauma was first reported by Metzenbaum in 1929 as being a causative factor in nasal septal dislocation. Since then, it has been reported by other authors. Deviated nasal septum in the newborn is said to occur due to various intrauterine and transnatal pressures operating on the fetus. In 1963, Klaff reported 12 cases of septal dislocation in newborns and went on to describe the causative factors and methods of treatment. Gray investigated septal deformities in 2,380 infants at birth and found anterior cartilage deformity in 4%. He put forward a maxillary moulding theory of transmitted pressure during pregnancy or birth in an attempt to explain septal deformities in the newborn. Hartikainen et al. screened 4,724 newborns for congenital nasal deformities and found a 1.9% incidence of anterior septal dislocation. In this study no evidence of birth trauma as the cause of congenital nasal deformities was found and it was proposed that the majority of dislocations originated during intrauterine life. Collo reported correction of 19 birth traumatic nasal septal deviations by manual manipulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1935711 TI - Management of odontogenic sinusitis with persistent oro-antral fistula. AB - Sixteen patients were treated for odontogenic sinusitis secondary to persistent oro-antral fistula. Males outnumbered females 12 to 4. Frequency of presentation increased directly with age. Chronic signs and symptoms included facial pain, swelling, tenderness and nasal and oral discharge. The clinical diagnosis of chronic sinusitis was confirmed in all cases by radiographic findings. An opacified maxillary sinus with or without ethmoid involvement was observed in all 16 patients. Surgical pathology revealed chronic mucosal thickening and/or antral polyps in 69% of the cases. Surgical treatment of the sinusitis consisted of antrostomy alone or in combination with Caldwell-Luc procedure. The oro-antral fistula was repaired with mucosal flaps from the buccal and/or palatal region. No postoperative recurrences have been noted during a follow-up period of six months to seven years. Bacterial cultures grew out pure aerobes (44%) or mixed aerobic anaerobic bacteria (44%). None yielded pure anaerobes. The bacteriologic spectrum was notably lacking in S. pneumoniae and H. influenzae and differed from organisms commonly found in sinusitis of rhinogenous origin. PMID- 1935712 TI - Sarcoidosis: a cause for bilateral facial palsy. AB - The facial nerve is commonly involved in neural sarcoidosis, but there is only one reported case in which bilateral facial paralysis was the sole manifestation of sarcoidosis. We report a case of sarcoidosis presenting with bilateral facial paralysis as the only sign. The pathology, clinical presentation, pathophysiology and diagnosis of sarcoidosis has been discussed. PMID- 1935713 TI - Topical anesthesia for peroral endoscopy. AB - Before the advent of safe and readily-available intubation anesthesia, most endoscopic procedures were carried out under topical or local anesthesia. Reawakening interest in cost effectiveness in medical practice and improved safety suggests that these techniques should be reexamined. The authors' experience in nearly 2,000 topical anesthetics for peroral endoscopy is reviewed. A preferred technique is presented which has proven effective and has resulted in an overall complication rate of less than 1%. PMID- 1935714 TI - Flexible fiberoptic laryngoscopy used to assess swallowing function. AB - Flexible fiberoptic laryngoscopy can be used to evaluate swallowing dysfunction by observing the patient's pharynx with a fiberoptic laryngoscope while the patient's swallowing function is challenged with various food materials. This technique provides much of the same information obtained from the formal videofluoroscopic swallowing examination and has the advantages of being a bedside technique requiring only a fiberoptic laryngoscope that can be performed in 15 minutes by a single otolaryngologist. PMID- 1935715 TI - Meibomian gland adenocarcinoma of the eyelid metastasizing to parotid lymph nodes. AB - Meibomian Gland Adenocarcinoma (MGA) is a rare tumor of the eyelid. We present two patients with this tumor that metastasized to the ipsilateral parotid nodes, along with a description of the disease and its response to various modes of treatment. PMID- 1935716 TI - Squamous cell carcinoma and lingual thyroid. AB - This report represents the first known case of squamous cell carcinoma associated with lingual thyroid tissue. Clinical examination of an exophytic mass at the base of tongue, CT imaging and a preoperative biopsy established a diagnosis of squamous cell carcinoma of the midline base of tongue. The therapeutic options and management of this carcinoma by surgical resection, irradiation or combined modalities were analyzed. The surgical option was chosen. This was accomplished via a midline labiomandibulo glossal split and primary repair of the wound. The final pathology report revealed a squamous cell carcinoma of the mucosa of the base of tongue directly over a benign lingual thyroid mass. Post-operative thyroid function studies were consistent with hypothyroidism and a thyroid scan confirmed the absence of thyroid tissue. PMID- 1935717 TI - Sensori-neural hearing loss in acute otitis media due to beta-hemolytic streptococcus successfully treated with penicillin and prednisone. AB - This article reports a case of a 21-year-old woman with acute otitis media with effusion secondary to a virulent group A beta-hemolytic streptococcus infection that led to rapidly deteriorating hearing in an only hearing ear. This deterioration continued despite middle ear ventilation and high-dose intravenous cefazolin and subsequent high-dose aqueous penicillin. The addition of prednisone to her therapeutic regimen led to rapid hearing improvement and decrease in effusion production. A historical perspective on the use of steroids in treating otitis media and several theories for this reversal in clinical course are presented. PMID- 1935718 TI - Liposarcoma of the nasopharynx: a case report. AB - We present a case of liposarcoma of the nasopharynx in a 28-year-old woman. The tumor was incompletely resected through an intraoral approach and supplementary radiotherapy of 50 Gy in a restricted field was therefore administered. Eleven years of follow-up show the patient to be disease free. PMID- 1935719 TI - Superficial carotid artery secondary to cervical teratoma. AB - Cervical teratomas are rare tumors, presenting as a mass in the neck at birth. Affected infants usually have respiratory compromise and dysphagia, secondary to tracheal and esophageal compression. Treatment consists of airway control, followed by surgical excision, which may be complicated by marked displacement of normal tissues. We present a case in which displacement of neck contents by mass effect resulted in a carotid artery course as close as 2mm from the skin surface. Radiographic and ultrasonographic documentation is included. PMID- 1935720 TI - Squamous cell carcinoma of the neck presenting as a chyle-filled pseudocyst. PMID- 1935721 TI - The use of Collagen Matrix to enhance closure of facial defects. AB - Facial defects created by removal of various types of skin cancer are usually closed primarily. There are some areas of the face where primary closure produces less than optimal results. We have utilized a non-reactive collagen sponge (Collagen Matrix) to enhance closure by secondary intention following removal of skin cancers. This presentation describes the properties of Collagen Matrix as well as the technique we utilized for closure of facial defects following tumor removal. PMID- 1935722 TI - Palatal inclusion cyst: an unusual complication of uvulopalatopharyngoplasty. AB - Inclusion cyst formation after uvulopalatopharyngoplasty has not been previously reported. We describe a case of postoperative inclusion cyst in a 62-year-old man who presented with recurrent obstructive sleep apnea symptoms. Simple transoral excision of the cyst was curative. Careful eversion of the mucosal edges at the time of the original palatal surgery may have prevented this problem from occurring. PMID- 1935723 TI - Helicobacter pylori: an infectious agent in peptic ulcer disease? PMID- 1935724 TI - Helicobacter pylori in peptic ulcer disease in Kenya. AB - Sixty six patients with dyspeptic symptoms underwent upper gastrointestinal endoscopy and biopsies for Helicobacter pylori culture. The number of H. pylori isolated increased with age reaching a peak at 51 to 60 years of age. Antral gastritis closely followed by duodenitis accounted for the highest number of H. pylori isolated, (87.5% and 85.7% respectively). In patients with duodenal ulceration only, 57% had H. pylori isolated from their antral biopsies, a result that was just slightly higher than that where no endoscopic diagnosis was made (50%). PMID- 1935726 TI - Gastric carcinoma in the Kenyan African population. AB - Fifty three consecutive patients with histological evidence of gastric carcinoma were studied between June 1987 and June 1989 at Kenyatta National Hospital (KNH). The male to female ration was 3.4:1 and the peak age of occurrence was in the 7th decade with 62.3% of gastric carcinoma being at the gastric antrum. Poorly differentiated adenocarcinoma was found in 68.2% of patients while well differentiated adenocarcinoma in 4.5% of cases. Intestinal metaplasia was a rare finding. If Lauren's classification of gastric carcinoma is considered then diffuse type of gastric cancer is by far the commoner type in our environment. PMID- 1935725 TI - A survey of colonic pathology with a double contrast method and analysis of the indication for a barium enema. AB - A prospective study of colonic pathology with double contrast method was made of 146 patients sent to the X-ray department of the Black Lion Hospital, Addis Ababa. The barium enemata were done for complaints like constipation, diarrhoea, rectal bleeding and palpable abdominal mass often without any relevant prior physical clinical examinations. Of those examined only 26 (17.8%) patients were found to have radiologically colonic pathology and the rest, 120 (82.2%) patients were reported normal. The policy of prior clinical examination before any barium enema such as rectal digital examination, sigmoidoscopy and stool occult blood studies would reduce the normal barium enema. The survey compared bowel preparation with adequate fluid intake and laxative without cleansing enema serves as a good method of bowel preparation for ambulatory patients. PMID- 1935727 TI - A study of haemorrhoids as seen at the Kenyatta National Hospital with special reference to asymptomatic haemorrhoids. AB - Eighty random patients were examined over a 9-month-period to determine the incidence of asymptomatic haemorrhoids at the Kenyatta National Hospital (KNH). The incidence of asymptomatic was found to be 21% all being first degree haemorrhoids, while in the age group 50 years and over, 29% had asymptomatic haemorrhoids. The mean age calculated as 44.3 years (+/- 18.3), with no statistical difference between the ages of the two sexes. Males however had a significant greater incidence of asymptomatic haemorrhoids than females. PMID- 1935729 TI - Adult polycystic liver disease. AB - Characteristics of 14 patients above 12 years of age with congenital polycystic liver disease attending liver clinic at KNH were analysed. The diagnosis was mainly based on ultrasonographic findings. The disease was found predominantly among the Kikuyu ethnic group with a female/male ratio of 6:1 and the peak age at presentation was in the 5th decade. The liver function tests were essentially normal in all cases with no complication directly relating to liver disease. Hypertension was found in 78.6% of cases and chronic renal failure in 35.7% of cases. There was an associated polycystic disease in at least one other abdominal organ in all cases. PMID- 1935728 TI - Intestinal colonization of rats following experimental infection with Campylobacter jejuni. AB - Oral infection of rats with 10(6)-10(8) colony forming units per ml of Campylobacter jejuni resulted in prompt intestinal colonization. Campylobacter jejuni was recovered from rat faecal samples for four months post infection. The colonized rats did not succumb to clinical diarrhoea or pyrexia. The resistance of rats to C. jejuni clinical infection and their ability to shed the organism for protracted periods, make rats potential source of zoonotic campylobacteriosis. PMID- 1935731 TI - Quality performance of metronidazole tablet products on the Kenyan market. AB - The in vitro performance of metronidazole tablet products by different manufacturers available on the Kenyan market was evaluated. It was found that a number of generic metronidazole tablet products have quality performance equal to that of Flagyl--the innovator product. All products confirmed to pharmacopoeial specifications. Three products with percent weight loss of 1.4, 11.08 and 14.93 failed the crucial friability test, for multidose packs. Two products failed the dissolution test releasing 46.8% and 45.8% of drug in 40 minutes. Drug release from tablet was found to vary between batches for one product. Ageing appears to decrease amount of drug released from tablets but longer storage periods and more samples are required before definite conclusions are drawn. PMID- 1935730 TI - Oxamniquine pharmacokinetics in healthy Kenyan African volunteers. AB - Oxamniquine pharmacokinetics were studied following oral administration of 750, 1000 mg or 1250 mg (equivalent to approximately 15 mg/kg) to five healthy Kenyan African volunteers. Peak plasma concentrations ranging between 1 and 4.3 mg/1 were achieved 1 to 4 h after dosing. The estimated mean elimination half-life (t1/2) was 2.2 h. Despite the limited number of subjects in the study, it is concluded that the pharmacokinetics of oxamniquine in healthy Kenyan Africans do not markedly differ from those in Africans from other regions of the continent where previous studies have been reported. PMID- 1935734 TI - Psychiatric morbidity and referral rate among medical in-patients at Kenyatta National Hospital. AB - Psychiatric morbidity among 200 medical in-patients at Kenyatta National Hospital was determined by a two-stage screening procedure, using the Self Reporting Questionnaire (SRQ) and standardized psychiatric interview (SPI). 44 (22%) of the total sample of 200 patients who were interviewed met the pre-established criteria for psychiatric morbidity; of these 59% comprised affective disorders. 4 (9%) of the psychiatric morbidity cases were referred for psychiatric evaluation. Referral seemed to be related to severity of illness and a previous history of psychiatric illness. There was no evidence in the notes that the psychiatric problems had been detected, treated or dealt with in any other way by the medical team in 34 patients out of 44 with psychiatric morbidity. Increase in the mental health input in the training of all health workers with emphasis on recognition and management of some of the commoner psychological problems is recommended. PMID- 1935732 TI - The intensity of Schistosoma mansoni in the fishing villages of Bugonga and Kitubulu in Entebbe Peninsula, Uganda. AB - The intensity of Schistosoma mansoni infection in the fishing villages of Bugonga and Kitubulu, and the occurrence of snail intermediate host population in the two villages are described and compared. A total of five hundred and six faecal samples from both villages were examined by modified Kato's technique and the prevalence infection rate at Kitubulu was 40.3% with mean egg count of 187 eggs per gram(epg) while in Bugonga it was 32.4% and 126 epg respectively. The snail intermediate host for S. mansoni in the two villages was 2,750 Biomphalaria choanomphala at Kitubulu and 1,268 at Bugonga. But at Kitubulu in the vicinity of the village 185 Biomphalaria peifferi occurred in small localized population. The cercarial screening test conducted on 4,018 B. choanomphala and 185 B. peifferi from the two villages revealed higher snail infection rate for both mammalian and non-mammalian cercariae at Kitubulu than Bugonga. Variations in infection rates both among the inhabitants and host snail populations in the two villages are discussed. PMID- 1935733 TI - Serum immunoglobin and complement levels in Ghanaian sickle cell patients in the steady asymptomatic state. AB - Serum IgM levels in sickle cell patients in the steady asymptomatic state were determined using radial immunodiffusion and found to be significantly higher than in health controls. Other immunoglobulins (IgA and IgG) were not significantly different from those of the controls. However concentrations of both C3 and C4 components of complements were significantly lower in sickle cell disease. This explains the low opsonization and chemotactic functions observed in these patients and further confirms the transient activation of the alternate pathway of complement. Abnormal complement C3 metabolism may explain the high susceptibility of patients to infections which contributes to the crisis in sickle cell disease. PMID- 1935735 TI - The role of laboratory medicine in psychiatry. AB - The application of contemporary biological methods in psychiatric practice has encouraged the reintegration of psychiatry into medicine. These investigative techniques assist in the elucidation of factors of aetiological importance, confirmation of diagnosis, regulation of dosage of medication, prediction of response to treatment and assessment of prognostic factors. It is emphasized that there is an urgent need to improve upon available laboratory facilities in mental health institutions in Africa and other third world countries, and also to encourage research in biological psychiatry. This will allow for cross-cultural comparison (between developed and developing countries) on the issue of aetiology, clinical manifestation/nosology, management and prognosis of mental disorders. PMID- 1935736 TI - An immunohistochemical study of bronchial cells producing surfactant protein A in the developing human fetal lung. AB - A study on immunohistochemical localization of pulmonary surfactant protein A (SP A) in the developing human fetal lung was performed using a monoclonal antibody, PE10, against human SP-A. At 21 weeks of gestation, a few bronchial cells positive to PE10 were observed to be scattered in the main and segmental bronchi. The number of these cells appears to increase until the 32nd week of gestation, and then decrease thereafter, almost disappearing by 39 weeks. On the other hand, alveolar type II cells and Clara cells positive to PE10 began to appear at 29 weeks, increase in number until around 39 weeks, and remain constant throughout adulthood. A few bronchial glandular cells positive to PE10 were still noticed in the fetal lung. This is the first report of the presence of SP-A-containing cells in the fetal lung. This is the first report of the presence of SP-A-containing cells in the human fetal bronchial epithelium (not Clara cells in the terminal bronchiolus), proving the regularity of the sequential distribution of SP-A containing cells in the bronchoalveolar system during pulmonary development. PMID- 1935738 TI - Pre-pregnant body size and spontaneous abortion of known karyotype. AB - We examined the relation of pre-pregnancy body size to chromosomally normal and chromosomally aberrant spontaneous abortion. Data derive from a hospital based case-control study of spontaneous abortion in the public and private facilities of three New York City hospitals. Chromosomally normal (n = 1265) and chromosomally aberrant (n = 872) spontaneous abortions (cases) were compared with 3795 women attending prenatal care before 22 weeks of gestation and delivering at 28 weeks or later (controls). Data on height and pre-pregnant weight were obtained by interview and Body Mass Index (BMI, weight/height squared) was computed. Associations were consistent across payment strata with disparate sociodemographic characteristics. BMI was similar in chromosomally normal cases and controls (pooled adjusted mean difference = 0.21 kg/m squared, 95% CI -0.06, 0.48) and reduced in chromosomally aberrant cases compared with controls (pooled adjusted mean difference = -0.29 kg/m squared, 95% CI -0.58, 0.00). These associations are unlikely to be due to reporting bias. However, they were of small magnitude and the association with chromosomally aberrant loss did not differ from that with chromosomally normal loss, nor was it specific to one, or even two, types of aberration. We therefore infer that, in relatively well nourished populations, low pre-pregnant body size does not increase the risk of either chromosomally normal or chromosomally aberrant spontaneous abortion. PMID- 1935737 TI - Developmental variation in whole human lung phosphatidylcholine molecular species: a comparison with guinea pig and rat. AB - Detailed analysis of the pattern of human and rodent lung phosphatidylcholine (PC) species during fetal development revealed a progressive increase in two disaturated species. The rise in the fractional content of dipalmitoyl PC (PC16:0/16:0) and myristoylpalmitoyl PC (PC14:0/16:0) was accompanied at each time point by a fall of similar magnitude in palmitoyloleoyl PC (PC16:0/18:1). Up to 20% of term lung PC was PC14:0/16:0. The temporal increase in rodent lung PC saturation began later in gestation than the human, and in the rat a significant increase in PC saturation only occurred postnatally. In this respect the guinea pig more closely resembled the human. For each mammal, a ratio of whole lung PC16:0/16:0 to PC16:0/18:1 (the P/O ratio) provided a sensitive marker of fetal lung maturity. The PC composition of whole adult lung and its saturation enrichment in bronchoalveolar lavage samples were similar in human, guinea pig and rat. We propose that the guinea pig provides a useful model for human lung prematurity studies. PMID- 1935739 TI - The effect of maternal height on birth weight and birth length. AB - This retrospective study examined the gestational age at which differences were observed between birth weights and birth lengths of infants whose mothers differed by height. Infants whose gestational ages were between 24 and 42 weeks born to women 59-62 inches (150-157 cm) tall were compared to similar infants born to women 66-69 inches (168-175 cm) tall. Significant differences occurred in birth weight and birth length from 35 weeks onward. The infants of the shorter women were symmetrically smaller than the infants of the taller women as the infant ponderal indexes did not differ. PMID- 1935740 TI - Vaginosonographic Doppler velocimetry in both uterine arteries: elevated left right differences and relationship to fetal haemodynamics and outcome. AB - Blood flow velocity was measured in both main stem uterine arteries by means of a transvaginally inserted Duplex scanner (240 degrees sector, pulsed Doppler) and visual vessel recognition to investigate normal and abnormal uterine perfusion. Its relationship to fetal circulation and fetal outcome was studied. Fetal vessels were investigated transabdominally. One hundred and seventy-six pregnancies with a high-risk for fetal malnutrition were examined between the 27th and the 40th week of gestation. In 113 (64%) patients we found normal uterine perfusion (A/B ratios in both uterine arteries less than 3, left-right difference less than 1) and in 63 (36%) cases the A/B ratios were outside our limits. A single abnormal A/B ratio in one of the uterine arteries or an abnormal left-right difference was classified as a mild form of abnormal uterine perfusion. Involvement of both uterine arteries was classified as a severe form. The severe form was associated with a higher frequency of pathological waveforms in fetal arteries and reduced fetal outcome. Clinically, velocimetry in both uterine arteries is of paramount importance when the degree of abnormal uterine perfusion is to be classified precisely. PMID- 1935741 TI - The emergence of adrenocortical circadian function in newborns and infants and its relationship to sleep, feeding and maternal adrenocortical activity. AB - The aim of this study was to assess basic information about adrenocortical activity and its correlates in newborns and infants until the age of 7 months. The circadian adrenocortical activity of 25 healthy infants (11 newborns and 14 3 7-month-olds) and their mothers was assessed from saliva. Additional information about infants' sleep and feeding was collected. In newborns, two-phase patterns of circadian adrenocortical activity were observed. Circadian patterns of adrenocortical activity seem to develop during the first 3 months. At three months adult-type patterns of circadian rhythm in adrenocortical activity were obvious. Stability of individual differences in newborns' cortisol levels was high. Correlates of infants' adrenocortical activity were found in sleeping and feeding patterns as well as in maternal adrenocortical activity. The development of the 24-h sleep-wake cycle paralleled the development of the circadian pattern in adrenocortical activity. The findings suggest that for an adequate interpretation of relationships between adrenocortical activity and behavior, information about basic cortisol levels and the temporal organization of feeding and sleeping must be considered. PMID- 1935742 TI - Assessment of gestational age in newborns by neurosonography. AB - Current methods for estimating gestational age using clinical parameters can be inaccurate in prematurity. A simplified ultrasonographic system, based on cerebral sulcal development, for clinically determining fetal maturation in newborns was developed and studied in 148 newborns (92 appropriate-for gestational-age, 54 small-for-gestational-age and 2 large-for-gestational age). This ultrasonographic sulcal method correlates better with the gestational age by dates than by the Dubowitz scoring system in the neonates less than 30 weeks' gestation. There are significant correlations between gestational age assessed by dates and by sonographic sulcal age in both appropriate-for-gestational-age (R = 0.91, P less than 0.001) and small-for-gestational-age newborns (R = 0.92, P less than 0.001). Maternal hypertension during pregnancy is a significant risk factor associated with accelerated fetal cerebral maturation in 12 neonates. Although overestimate of gestational age may occur in neonates born to mothers with hypertension, cranial ultrasonography is an accurate and convenient method of estimating gestational age in neonates. PMID- 1935743 TI - [Cuba: the hospital-physician interrelationship of the family within the strategies of primary health care]. PMID- 1935744 TI - [Data collection for nursing research in Brazil. Strategies, validity and confidence]. PMID- 1935746 TI - [Guatemala: the participation of the College of Medical Sciences of the university of San Carlos in community projects in health development]. PMID- 1935745 TI - [Mexico: the training of human resources in health economy]. PMID- 1935748 TI - [INCAP: update of medical knowledge using long distance educational techniques]. PMID- 1935747 TI - [Bolivia: analysis of the utilization of graduates with a Masters in public health]. PMID- 1935749 TI - [Colombia: effects of a structured educational program on the attitude of the elderly to old age]. AB - Twenty-nine elderly were assessed on the attitudes toward aging before and after attending to an Estructural Educational Program (EEP), with a participative methodology. The program's objective was to strength and reorient the attitudes of aceptation, integration and communication. Subjects have been part of an urban sector of low social economical status from Cali, Colombia. A quasiexperimental research design, with a convenient sample was used. It was applied a questionnaire to each subject to collect biopsychosocial data, a Lickert scale before and after the EEP to measure attitudes, as well as an observational guide to measure individual and group behavior before and after each class. A statistical significative growth was observed on the attitudes toward integration, aceptation and communication (t22 = 2.46 p less than 0.05). Data indicated that elderly attitudes can be strengthened and reoriented through a EEP adjusted to the biopsychosocial characteristics of the group. PMID- 1935750 TI - [Veterinary science and society: reflexions on the professional paradigm]. PMID- 1935751 TI - A smoking cessation program for the dental office: the time is right! PMID- 1935752 TI - [Results of the 4th International Conference on computerized and quantitative EMG procedures]. PMID- 1935753 TI - [Spinal and subcortical somatosensory evoked potentials: a comparison with the localization of spinal, medullary and pontine lesions and in brain death]. AB - The spinal and subcortical median nerve SEPs were recorded in 65 patients with lesions of the cervical cord, medulla oblongata, pons and in brain death. A recording technique including cephalic, non-cephalic and anterior neck referenced leads was used. The location of the lesions corresponded to different types of SEP alterations: Cervical extramedullary lesions compressing the spinal cord corresponded to a prolonged P9-P14 interpeak latency. Cervical intramedullary lesions corresponded to the loss of N13, normally generated in the spinal interneurons. Vascular lesions of the medulla oblongata (Wallenberg's syndrome) showed normal SEPs. Space occupying medulla oblongata lesions corresponded to reduction in amplitude or loss of P14. Pontine lesions showed normal spinal and subcortical SEPs. In brain death P14 showed a graduate decrease in amplitude or alternatively vanished abruptly. The spinal and subcortical SEPs provide a good tool for testing the function of the lemniscal pathways and the spinal interneurons. PMID- 1935754 TI - [Analysis of the generators of early cortical somatosensory evoked potentials (N. medianus) using dipole source analysis: initial results]. AB - There is still much controversy about the contribution of the brainstem, the thalamus and the somatosensory and motor areas of the various scalp recorded peaks of the somatosensory evoked potentials (SEP) after median nerve stimulation. This study addressed the generator problem of the scalp recorded potentials using brain electric source analysis. In 11 normal subjects median nerve SEPs were recorded from 32 locations. The brain-electric-source-analysis revealed a minimum of 5 sources with overlapping activities in the interval of 12 35 ms post stimulus. The initial deflections were in the time range of the scalp peaks (P14, P18, N20, P22, N30), but there was no single source to fully explain a scalp peak except for the brainstem source of P14. The other sources appeared to reflect activities of the thalamo-cortical-pathway (P18), of the somatosensory areas 3b (N20) and 1 (P22) and of a fifth source (contribution maximal around 30 ms) with no consistent location. The close location of multiple sources makes the precise separation and localisation of the various sources quite difficult in individual data sets. PMID- 1935755 TI - [Experience with computer-assisted EMG analysis: reference values for four muscles]. AB - The characteristics of a newly developed computerized EMG-analysis system are lined out. The analysis steps include segmentation and parametrization of digitized EMG segments followed by automatic classification of single potentials into motor units. Comparison of parameters is used rather than a template matching algorithm for classification. For each motor unit a set of parameters can be computed in addition to duration and amplitude. Normative data are given for four muscles. 60 normal volunteers (50% female, 50% below age 50) were recorded from for each muscle. The recording conditions required to move the electrode until a motor unit could be recorded with its individual maximum. Furthermore, it was attempted to attain the maximum discharge rate of a particular motor unit. A highly significant correlation of the amplitude of the motor unit potentials with age was found for all four muscles. For the duration of the potentials a correlation with age was found only for the M. ext. digitorum brevis. Significant sex differences were found for nearly all parameters and all muscles. Pairwise comparisons of the muscles revealed significant differences of all muscles. The analysis showed, that a muscle can be regarded pathological if more than two of a total of seven recorded motor units show pathological parameters. PMID- 1935756 TI - [Methodologic studies in dynamic EMG mapping based on the Hilbert transformation]. AB - On the basis of Discrete Hilbert Transformation spectral parameters for dynamic EMG analysis can be introduced. Within analysis intervals which are used in the same manner as in spectral analysis, the momentary power of EMG frequency bands can be computed as time series of the same interval duration. A close connection exists between momentary power and the current phenomenology of power spectral analysis because the momentary power of a defined frequency band can be seen as the exact dynamic equivalent of the corresponding mean power value deduced from the power spectrum. A multichannel EMG recording (greater than or equal to 16 channels) makes the representation of the topographical distribution of the spectral parameter by a coloured map possible. Additionally, the momentary power can be used to calculate map sequences. In this way, changes of EMG activity can be quantified by map sequences of an arbitrary time resolution. By calculation of momentary frequency via DHT an artefact detection scheme for ECG interference can be suggested. A completion of this methodology can be carried out by applications of adaptive filtration procedures. Using this concept of EMG processing, a new and common methodical basis of EMG power spectral analysis can be introduced. PMID- 1935757 TI - [Dose-response relationships between blood alcohol concentrations and cognitive potentials (visual P300) in man]. AB - 20 healthy male subjects with a mean age of 24 +/- 2.7 years were intravenously administered a mean total dose of ethanol of 1.33 +/- 0.04 g ethanol/kg body weight using a perfusor device. The ethanol kinetic resulted in a "rising phase" of 90.2 +/- 0.9 min. in average. The PFP300 parameter in this phase of acute alcohol intoxication showed the following changes: Along with the increasing blood alcohol level the N250- and PFP300a-latencies of both the A- and B potentials are progressively prolonged and the ascending PFP300-amplitudes are progressively reduced. The N250-latency of the B-potentials is shown to be the most sensitive parameter of the PFP300-complex already changing at a blood alcohol concentration (= b.a.c.) of 0.59 +/- 0.11% with a mean linear prolongation of 2.5 ms per 0.1 g ethanol/kg body weight. This prolongation reflects the increasing disability of the subjects to discriminate between task relevant and task-irrelevant stimuli at b.c.a.-levels much below that being presently permitted for driving in the Federal Republic of Germany. PMID- 1935759 TI - F-wave study at different stimulation rates. AB - In 50 ulnar nerves of healthy subjects, F-wave latency, duration, amplitude and persistence were determined at different frequencies of the antidromic impulse (0.2-0.5-1-2 Hz). The F amplitude and persistence were found significantly increased at higher stimulation rates, suggesting that the frequency of the antidromic impulse influences the motoneuron pool discharges. Individual cross correlation values (r) obtained for latency and duration, latency and amplitude, amplitude and duration did not show any significant changes at different stimulation rates. PMID- 1935758 TI - Oscillatory firing of single human sphincteric alpha 2 and alpha 3-motoneurons reflexly activated for the continence of urinary bladder and rectum. Restoration of bladder function in paraplegia. AB - 1. By recording with 2 pairs of wire electrodes from human sacral nerve roots (S3 S5) rhythmic as well as occasional firing was observed in alpha 2 and alpha 3 motoneurons in response to physiologic stimulation of the urinary bladder and the anal canal. The rhythmic firing consisted of periodically occurring impulse trains, most likely produced by true spinal oscillators which drove the motoneurons. 2. Alpha 2-motoneurons, innervating fast fatigue-resistant muscle fibres, were observed to fire with impulse trains of about 2 to 4 action potentials (Ap's). These impulse trains occurred every 110 to 170 msec (5-9 Hz). Alpha 3-motoneurons, innervating slow fatigue-resistant muscle fibres, fired about every 1400 msec (approximately 0.7 Hz) with impulse trains of about 11 to 60 Ap's. Alpha 1-motoneurons, innervating fast fatigue muscle fibres, and gamma motoneurons were not observed in the continuous oscillatory firing mode. 3. Sphincteric motoneurons were observed most likely in the oscillatory firing mode in response to the sustained stretch (reflex) of the external and sphincter or to retrograde filling of the bladder (urethro-sphincteric guarding reflex), in order to preserve continence. A urethral sphincteric alpha 2-motoneuron increased its mean activity from 0.5 to 18 Ap's/sec during retrograde filling by changing its firing pattern from the occasional spike mode via the transient oscillatory firing mode to the continuous oscillatory mode. Up to a filling of the bladder of 500 ml the mean activity of the stretch receptors, measuring probably mural tension, increased roughly proportionally and the sphincteric motoneuron increased its activity to about 1 Ap/sec in the occasional spike mode. Up to 600 ml, the motoneuron responded in the transient oscillatory mode with mean activities of up to 5 Ap's/sec. With higher bladder fillings, the flow receptors afferents fired additionally, probably according to pressure symptoms, and the motoneuron switched into the continuous oscillatory firing mode and increased its activity up to 18 Ap's/sec at 700 ml. When the bladder was about 800 ml full, the stretch afferent activity decreased, the flow receptor activity increased strongly and the alpha 2-motoneuron activity decreased; the overflow incontinence had probably started. Micturition was not observed, probably because of brain death. 4. It is suggested that one adequate stimulus for an alpha 2-motoneuron of the external anal sphincter to jump into the oscillatory firing mode, was the activity from secondary spindle afferent (SP2) fibres from external anal sphincter muscle spindles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935760 TI - Bilateral small-hand-muscle motor evoked responses in a patient with congenital mirror movements. AB - In a 56 year old patient with congenital mirror movements involving the muscles of the hands and forearms, transcranial electrical stimulation of either the left or right motor-cortex hand area induced bilateral surface electromyographic (EMG) responses in the abductor pollicis brevis (APB) muscles with normal latencies (21 msec). Slight volitional background contraction of the APB muscle contralateral to the stimulated motor cortex enhanced the motor evoked potential (MEP) and shortened the latency of the response by about 3 msec, while no definite facilitation was detected in the ipsilateral APB muscle. Volitional activation of the APB muscle ipsilateral to the stimulated motor cortex failed to enhance the response or shorten the latency of the response in either APB muscle. It is concluded that a fast conducting uncrossed or double crossed corticospinal system plays an important role in the execution of ipsilateral involuntary mirror movements and may be explained by aberrant reorganization of the pyramidal system. PMID- 1935761 TI - CNS involvement in chronic inflammatory demyelinating polyneuropathy: an electrophysiological and MRI study. AB - Eight consecutive patients with chronic inflammatory demyelinating polyneuropathy (CIDP) were investigated by visual evoked potential (VEP), brainstem auditory evoked response (BAER) and magnetic resonance imaging (MRI) to assess central nervous system (CNS) involvement. VEPs were abnormal in 6 patients and BAERs in 2. MRI showed changes suggestive of CNS demyelination in 2 cases. Our findings suggest the existence of a combined central and peripheral demyelinating syndrome and emphasize the possibility of a common pathogenetic mechanism for both. PMID- 1935762 TI - Quantitative evaluation of the motor unit potential complexity. AB - A method for MUAP complexity evaluation is proposed. A complexity coefficient intended for measuring potential complexity is defined, it is a product of filling factor and coefficients measuring the variability of signal parameters. This coefficient has been used to estimate quantitatively the degree of complexity and hence to order a set of potentials. The potential ordering agrees with intuitive expectation. So, it seems that this method may be appropriate for complexity evaluation, and could be applied in the study of remodeling process in neuro- and myopathic diseases. PMID- 1935763 TI - Electrophysiologic investigation of benign eyelid twitching. AB - A 48 year old woman presented with a 5 year history of intermittent right eyelid twitching. Electromyography of the right lower eyelid revealed myokymic discharges. Blink reflex study revealed a contralateral R1 on stimulating the left, but not the right, supra-orbital nerve. Sensory and auditory evoked potentials were abnormal, pointing to possible brainstem lesions. Oligoclonal bands were present in the cerebrospinal fluid. Magnetic resonance imaging of the brain was normal. This case report demonstrates that benign eyelid twitching can be a localized form of facial myokymia and may be a manifestation of underlying brainstem disease. PMID- 1935764 TI - Henry Stanley Plummer. PMID- 1935765 TI - Remembrance of Dr. Alfred Jost. PMID- 1935766 TI - The early days of steroid radioimmunoassays at the Worcester Foundation. PMID- 1935767 TI - Morphogenetic and proliferative effects of testosterone and insulin on the neonatal mouse seminal vesicle in vitro. AB - Effects of testosterone (T) and insulin on epithelial branching morphogenesis were investigated in cultured seminal vesicles (SVs) of neonatal mice. SVs from 0 day-old male mice were cultured for 0.5-6 days in serum-free chemically defined medium in the presence of T (10(-7) M), insulin (10 micrograms/ml), or T plus insulin or in medium lacking both hormones. Without the addition of both hormones, SVs failed to grow, based on DNA and protein contents, and did not show any epithelial branching morphogenesis. T induced a 2.5-fold increase in protein content in SVs cultured for 6 days and elicited modest epithelial branching morphogenesis. Insulin increased the protein content of cultured SV rudiments as much as T, but failed to elicit epithelial branching morphogenesis. The combination of both hormones induced a 4.3-fold increase in protein content in cultured SVs and elicited more extensive epithelial branching morphogenesis than T alone. Epithelial and mesenchymal DNA contents in SVs declined slightly during the first 12 h of culture in all treatment groups. The epithelial DNA content in SVs grown with insulin alone remained constant thereafter, while that of SVs grown with T alone or in combination with insulin increased 1.2- and 2.6-fold, respectively. In the absence of both hormones, the mesenchymal DNA content remained constant in SVs grown for 6 days after the initial decline in DNA content. In contrast, mesenchymal DNA content was increased to the same degree (1.4-fold) by either T or insulin alone or in combination. The labeling index with [3H]thymidine of SV epithelium and mesenchyme grown under the hormonal conditions described above corroborated the results of epithelial and mesenchymal DNA contents. These data indicate that insulin by itself has no effect on epithelial proliferation and branching morphogenesis in the neonatal mouse SV, but, instead, amplifies the morphogenetic and proliferative effects of androgen on the developing mouse SV, thus eliciting extensive branching morphogenesis. Both insulin and T have a slight (nonsynergistic) effect on proliferation of SV mesenchyme. Analysis of androgen metabolism in developing mouse SVs indicated that dihydrotestosterone was the major product when T was used as substrate in SVs grown under all hormonal conditions. The rate of DHT production per 100 mg protein was not significantly different among the different treatment groups. Higher levels of 5 alpha-androstane-3 alpha,17 beta-diol were detected in SVs grown in the absence vs. the presence of T regardless of the presence or absence of insulin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935768 TI - The role of thyroid hormone in the regulation of hepatic carbamyl phosphate synthetase activity in Rana catesbeiana. AB - Both spontaneous and thyroid hormone (TH)-induced metamorphosis of Rana catesbeiana are accompanied by a marked increase in the activity of the urea cycle enzyme carbamyl phosphate synthetase (CPS). The increase induced by exogenous TH is de novo synthesis of enzyme and appears to be secondary to an increase in the CPS mRNA level resulting from the elevated plasma TH. Since endogenous TH levels rise sharply during spontaneous metamorphosis, a similar sequence of events would be anticipated. However, after midclimax, CPS activity continues to increase, while plasma TH levels steadily decline, suggesting that other factors are involved. To obtain insight into this problem, the changes in CPS mRNA level during spontaneous development were determined using a mammalian CPS cDNA probe and correlated with changes in CPS activity and plasma T3 concentration. CPS mRNA level and CPS activity were barely detectable until midprometamorphosis, but both increased rapidly during the latter half of this phase. CPS activity continued to rise, reaching a maximum in the adult frog. The CPS mRNA level, however, was highest during the first half of climax, but declined after midclimax and was relatively low in the adult frog. Studies were also performed in which the rise and fall in the plasma T3 concentration typical of metamorphic climax were induced by exposure of premetamorphic tadpoles to T3, followed by its withdrawal. Both CPS activity and CPS mRNA level were induced by T3, but when plasma T3 levels fell after removal of the exogenous T3, CPS mRNA level, but not CPS activity, also decreased. Additional studies indicated that the TH-induced increase in CPS mRNA was evident within 24 h, could be prevented by simultaneous injection of actinomycin-D, and could not be induced in tadpoles undergoing climax; in this phase the T3 receptors are fully occupied with endogenous TH. When premetamorphic tadpoles were immersed in T3-containing water (0-500 nM) for 6 days, CPS mRNA, CPS activity, and plasma T3 concentration increased in parallel, reaching a maximum at 50 nM. At 50 nM T3, the plasma T3 level was sufficient to saturate the receptors, and no additional increase in CPS mRNA level or CPS activity was obtained at higher concentrations of T3. These studies indicate that the CPS mRNA level during spontaneous development correlates with the plasma T3 concentration and suggest that it is a function of T3 receptor occupancy. The data are also consistent with an effect of TH on transcription of the CPS gene and with a relatively long half-life of its protein product, the CPS enzyme. PMID- 1935769 TI - Pituitary-placental interaction: hypophysectomy modulates the secretion of mouse placental lactogen-I. AB - To determine whether the pituitary gland influences the concentration of mouse placental lactogen-I (mPL-I) in maternal serum, pregnant Swiss Webster mice were hypophysectomized or sham-operated on day 9 of gestation. Blood was collected on days 10-13 and 18, and the mPL-I concentration of the serum was measured by RIA. The serum mPL-I concentration of hypophysectomized mice was significantly higher than that of sham-operated and intact mice on days 10-13. There was no difference in mPL-I concentration on day 18 of pregnancy among the groups. Similar elevations in serum mPL-I concentration were observed when hypophysectomy was performed on day 10 of pregnancy. Steady state levels of placental mPL-I messenger RNA (mRNA) were analyzed by Northern hybridization. No differences were observed in the amount of mPL-I mRNA among hypophysectomized, sham-operated, and intact mice. These results demonstrate that the pituitary gland exerts inhibitory control over the maternal serum mPL-I concentration. This control does not appear to be affected at the level of steady state amounts of mPL-I mRNA. PMID- 1935770 TI - Transforming growth factor-beta: role in mediating serum-induced endothelin production by vascular endothelial cells. AB - Studies were performed to characterize the identity of the factors present in calf serum that stimulate endothelin (ET) production by vascular endothelial cells in culture. Two putative candidates responsible for the ET-releasing activity present in serum are members of the transforming growth factor-beta (TGF beta) superfamily, TGF beta 1 and activin A. TGF beta 1 antiserum was used to block the actions of TGF beta 1, and follistatin was used to block the actions of activin. Treatment of serum with TGF beta 1 antiserum attenuates ET production by vascular endothelial cells. TGF beta 1 antiserum (1 microliters) completely prevents the release of ET produced by 0.1% and 0.3% serum. Follistatin is a potent inhibitor of activin-induced ET release but does not alter serum-induced ET production. Because serum-induced ET release is dependent on TGF beta, it may be a physiological regulator of ET production by vascular endothelial cells. PMID- 1935771 TI - The relationship between prorenin levels in follicular fluid and follicular atresia in bovine ovaries. AB - Bovine follicles having a higher concentration of progesterone than estradiol in the follicular fluid can be considered as atretic. Since we observed previously that there was an inverse relationship between the follicular fluid estradiol to progesterone (E/P) ratio and the prorenin level, we have proposed that a high prorenin level may be associated with follicular atresia. The aim of the present study was to corroborate this hypothesis by including additional indices to distinguish unambiguously between atretic and nonatretic follicles and to compare the prorenin levels in these two groups of follicles. The present study included examination of more than 200 follicles in the follicular fluid of which we have measured steroid and prorenin levels. The results obtained show a highly significant negative correlation between the prorenin level on the one hand and the E/P ratio, estrogen to total androgen ratio, or estradiol concentration on the other hand. As a further criterion for atresia, we have examined the histological characteristics of the follicles by light and electron microscopy and have found that 90% of histologically characterized atretic follicles had an E/P ratio less than 1 and an average prorenin level four to five times higher than nonatretic follicles. Finally, when we determined the FSH-stimulated cAMP response and the aromatase activity, in terms of the ability to convert exogenous androgen to estrogen in granulosa cells isolated from individual follicles, we observed a markedly higher prorenin level in the fluid of follicles whose granulosa cells responded poorly to FSH and showed a low aromatase activity, compared to follicles whose granulosa cells responded strongly to FSH and contained high aromatase activity. In summary, follicles that were classified as atretic on the basis of a number of biochemical and histological parameters contained significantly higher prorenin levels in their follicular fluid than nonatretic ones. Thus, a high follicular fluid prorenin level is a valid indicator for follicular atresia in bovine ovaries. However, the reason for this increase in follicular fluid prorenin level and whether this increase is a cause or a consequence of atresia remains to be determined. PMID- 1935772 TI - Sex steroids and growth factors differentially regulate the growth and differentiation of cultured human endometrial stromal cells. AB - We have studied the interaction between growth factors and sex steroids in regulating human endometrial stromal cell growth and differentiation using an in vitro serum-free cell culture model system. None of the growth factors [epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin, insulin-like growth factor-I (IGF-I), IGF-II, or platelet-derived growth factor] stimulated the growth of human endometrial stromal cells grown in progestin-free medium. However, the growth of progestin-treated cultures was dramatically increased by EGF, bFGF, or platelet-derived growth factor, but not by insulin, IGF-I, or IGF II. Estrogen could not substitute for progesterone in this protocol, and coadministration of estrogen with progestin did not enhance the response over that to progesterone alone. In contrast to their positive effects on growth, only EGF, not bFGF, stimulated stromal cell differentiation, as measured by an increase in PRL, laminin, and fibronectin production; moreover, stimulation of differentiation was dependent upon the presence of progestin in the culture medium. Thus, human endometrial stromal cell growth is 1) regulated by a discrete set of growth factors, only a subset of which regulates stromal cell differentiation; and 2) regulation of stromal cell growth and stromal cell differentiation by growth factors is progestin dependent. Our results provide direct evidence for interaction between growth factors and sex steroids in the regulation of stromal cell growth and differentiation in vitro and suggest that growth factors may be absolutely required in conjunction with progesterone for the decidual response in vivo. PMID- 1935773 TI - Estradiol negatively regulates secretogranin II and chromogranin A messenger ribonucleic acid levels in the female rat pituitary but not in the adrenal. AB - Estradiol (E2) effects on the pituitary and adrenal secretogranin II (SgII) and chromogranin A (CgA) proteins and mRNA levels were analyzed in the adult female rat. Animals were ovariectomized or sham-operated for 2 weeks and then daily injected with various doses of 17 beta-E2 (from 5-100 micrograms) for the following week. SgII and CgA levels were determined by Western blot analysis using two specific antisera. Messenger RNA (mRNA) levels were measured by RNA slot blot analysis using specific cDNA probes. Simultaneously, pituitary LH content and gonadotropin subunit (LH beta, FSH beta, alpha) mRNAs were quantified. Ovariectomy promoted a significant increase in pituitary SgII and CgA proteins (2-fold vs. sham-operated animals, P less than 0.01) and a concomitant rise in their mRNA levels (2.5-fold and 4.5-fold for SgII mRNA and CgA mRNA, respectively, P less than 0.01). In the same animals LH beta, FSH beta, and alpha subunit mRNA levels increased by 20-, 12-, and 6-fold, respectively. Estrogen replacement resulted in a parallel decrease of CgA and LH beta mRNA to the control values, starting from the lowest steroid dose (5 micrograms). The SgII mRNA decrease was initiated only with a higher concentration of E2 (10 micrograms), as was that of alpha-subunit mRNA; yet, the SgII mRNA level remained significantly higher than in the control pituitary, even with the highest steroid dose (P less than 0.05) at variance with the alpha-mRNA level. Concerning protein concentration, the postcastration increase in CgA was fully reverted with 10 micrograms E2 while that of SgII remained unaffected, as was the pituitary LH content. In the adrenal gland, neither the ovariectomy nor the E2 therapy altered significantly the SgII or CgA protein and mRNA concentrations. We conclude that, in rats, 1) ovarian factors regulate the pituitary SgII and CgA protein and mRNA steady-state levels while such factors are inefficient in the adrenal gland, 2) CgA and LH beta mRNAs exhibit the same sensitivity to E2 while SgII and alpha subunit mRNAs appear less sensitive, and 3) SgII and LH pituitary contents present a similar pattern of variations when the estrogenic status of the animal is modified. PMID- 1935774 TI - Changes in basic fibroblast growth factor coincident with estradiol-induced hyperplasia of the anterior pituitaries of Fischer 344 and Sprague-Dawley rats. AB - Adult female Fischer 344 (F344) and Sprague-Dawley (SD) rats were treated with estradiol via Silastic implants for 10 and 20 days. This treatment period in F344 rats is sufficient to produce dramatic hyperplasia of anterior pituitary lactotropes, activation of folliculo-stellate cells (FS) as phagocytes, and reorganization of the blood supply, i.e. hemorrhagic lakes and arteriogenesis from vessels in the adjacent meninges. Estradiol-treated SD rats do not demonstrate a comparable response. We now report intense focal concentrations of cells immunopositive for basic fibroblast growth factor (FGF) in estradiol treated F344 rats predominantly near the posterolateral edge of the anterior pituitary, a zone rich in gonadotropes and lactotropes. Immunostaining for FGF, by both light and electron microscopy, revealed that the immunopositive cells were gonadotropes, and that the immunoprecipitate was cytosolic and was most abundant in the cytosol facing the capillaries. Immunostaining for extracellular matrix-associated FGF also revealed foci of positivity at the postero-lateral edge. Estradiol-treated SD rats did not reveal comparable localization for FGF. Morphological analysis and immunolocalization of S-100 protein, a marker for FS cells, revealed that the periphery of the anterior pituitary of estradiol-treated F344 rats included numerous disrupted gonadotropes and, furthermore, was largely devoid of FS cells. This zone was more intact in control F344 rats, but lacked FS cells. The peripheral parenchyma of control and estradiol-treated SD rats was intact compared to that of F344 rats and consistently included FS cells. These results suggest that disruptions of gonadotropes at the pituitary periphery may release FGF, which could then stimulate angiogenesis from blood vessels within the adjacent meninges. The resultant systemic blood supply would stimulate lactotrope hypertrophy and hyperplasia. Since FS cells are known phagocytes within the anterior pituitary, their absence from the periphery of F344 rats may intensify or prolong the effect of the peripherally released FGF. PMID- 1935775 TI - Biochemical identification of apoptosis (programmed cell death) in granulosa cells: evidence for a potential mechanism underlying follicular atresia. AB - In the present study, we examined the possibility that granulosa cell death during ovarian follicular atresia occurs by apoptosis (programmed cell death). To investigate this possibility, atresia was induced in immature female rats by injecting 15 IU PMSG. Controls received either vehicle or no treatment. PMSG treated animals were killed on days 1-5 post-injection while controls were killed on days 1 or 5. The onset of atresia was assessed histologically by light microscopic inspection of 5 microns tissue sections and functionally by quantification of serum progesterone and estrogen levels. Apoptosis is characterized by the cleavage of genomic DNA into oligonucleosomal length fragments by a Ca2+/Mg(2+)-dependent endogenous endonuclease. Such fragments form a distinctive ladder pattern when separated electrophoretically. Accordingly, the occurrence of apoptosis in granulosa cells was assessed by examining the pattern of fragmented DNA in cell lysates after agarose gel electrophoresis. Gels were stained with ethidium bromide and DNA visualized by UV transillumination. The earliest morphological signs of atresia were detected 4 days after PMSG injection as evidenced by degeneration and detachment of granulosa cells from the basal lamina. Serum estrogen increased from basal to levels 7-fold over controls by day 3 after PMSG treatment, falling to control values by day 4 and thereafter. In contrast, progesterone remained basal for the first 3 days, rising to levels 3 fold and 8-fold above controls 4 and 5 days after PMSG treatment, respectively. Such shifts in the ratio of estrogen to progesterone production are known to be characteristic of follicular atresia. Finally, electrophoretic analysis of low mol wt DNA in granulosa cell lysates revealed a definitive ladder pattern of oligonucleosomal length DNA fragments (characteristic of apoptosis) on days 4 and 5 after PMSG injection. This pattern was not detectable on days 1 and 2 after treatment. Lysates obtained 3 days after PMSG treatment showed a faint apoptotic like pattern of DNA fragments; a result consistent with other systems in which DNA cleavage begins before any morphological signs of death. Interestingly, a ladder pattern of DNA fragments was present in control lysates suggesting that granulosa cell death under normal (vs. induced) conditions of atresia in immature rats occurs by apoptosis. These data demonstrate an intimate association between apoptotic-like events and dying granulosa cells and thus support the possibility that apoptosis is involved in the induction of follicular atresia. PMID- 1935776 TI - Diethylstilbestrol stimulates persistent phosphatidylinositol lipid turnover by an estrogen receptor-mediated mechanism in immature mouse uterus. AB - The effect of estrogen on phosphoinositide (PI) metabolism was evaluated in the immature mouse uterus, a tissue which undergoes estrogen-induced proliferation. Uteri isolated from untreated mice or from mice injected ip with diethylstilbestrol (DES) were incubated with [3H]myo-inositol and assessed for incorporation of label into PI lipids or inositol phosphate generation. DES administration elicited a rapid increase in [3H]myo-inositol incorporation, which persisted until at least 18 h post treatment. This effect could not be duplicated by incubation of uteri with DES in vitro, although [3H]myo-inositol incorporation in uteri removed from DES-treated mice remained elevated for 3 h of in vitro incubation. Stimulation of PI lipid metabolism by DES was blocked by ICI 164,384, a specific estrogen receptor antagonist. The effect of DES on PI metabolism consisted of a time-dependent increase in the specific activity of both phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate and a significant increase of inositol (1,4,5)-trisphosphate mass by 12 h post treatment. These changes occur before the onset of estrogen-induced DNA synthesis. The results indicate that estrogens rapidly modulate PI lipid turnover through an estrogen receptor-mediated mechanism. Since the metabolic products of PI lipids are important for signal transduction and cellular proliferation, altered metabolism of these lipids may play an integral role in estrogen-induced mitogenesis. PMID- 1935777 TI - Kinetics of cytosolic calcium and aldosterone responses in rat adrenal glomerulosa cells. AB - To evaluate the relationship between cytosolic calcium (Cai) and aldosterone production, rat adrenal zona glomerulosa (ZG) cells were studied during long-term stimulation by different secretagogues. Cai was measured in single ZG cells using microspectrofluorimetry, and aldosterone was determined in cell populations using a superfusion system. For external potassium (K+), Cai increases are sustained, with only a slight decrement over time, a feature shared by aldosterone production. The relationship between aldosterone output and Cai is nonlinear, with a Cai value for half-maximal stimulation of approximately 500 nM. Furthermore, the sustained changes in Cai with external K+ indicate that ZG cells can use an amplitude-based Cai signal to stimulate aldosterone production. Cai changes stimulated by angiotensin-II (Ang-II) show a complex dose-response pattern, with high concentrations (greater than or equal to 1 nM) of Ang-II eliciting a peak-plateau signal and lower doses (0.1 nM to 10 pM) producing repeated Cai oscillations. The peak amplitude of the Cai response in individual cells is not dose dependent, with the ZG cell experiencing peak levels repeatedly at the lowest Ang-II concentrations. However, the Cai transients are more frequent with increasing Ang-II concentrations between 0.1 nM and 10 pM. When integrated over time, the mean Cai signal also shows only modest dose-dependency during the sustained phase of Ang-II stimulation. Unlike the integrated Cai signal, aldosterone production increases steeply between 10 pM and 0.1 nM Ang-II, indicating that the Cai signal is likely to be frequency-based. Conversely, the steroid response to high Ang-II closely mirrors the kinetics of the more sustained Cai signals, including the diminished Cai and aldosterone levels during sustained stimulation with the highest Ang-II doses. Arginine vasopressin stimulated Cai and aldosterone responses, which closely resemble those elicited by 0.1 nM Ang-II, except that both Cai and aldosterone return to basal values within 20 min of continuous presentation of arginine vasopressin. Each ZG secretagogue produces a distinct pattern of Cai and aldosterone response. In addition, Cai response patterns can be divided into two general classes: a sustained Cai response, which appears to modulate cell activation by the amplitude of the Cai signal, and an oscillating Cai response, which uses the frequency of the Cai transients to control the magnitude of stimulation. PMID- 1935778 TI - Age-related decreases in serum gonadotropin levels and gonadotropin-releasing hormone gene expression in the medial preoptic area of the male rat are dependent upon testicular feedback. AB - In the male rat, age-associated reproductive decline is thought to be due in part to diminished GnRH secretion. We tested the hypothesis that the age-related decrease in GnRH secretion is due to decreased GnRH gene expression by comparing GnRH mRNA and peptide content in the anterior forebrain of intact young and old male rats. Since sex steroids modulate GnRH secretion, we also determined hypothalamic-pituitary responsiveness to removal of testicular feedback by comparing GnRH mRNA and gonadotropin levels in intact and orchidectomized young and old rats. In an initial study, 10 20-micron coronal sections from the medial preoptic area (MPOA) were anatomically matched and compared in intact young (3 month-old) and old (24-month-old) male F344 rats (n = 5/group). In another group of young and old male rats (n = 8-12/group), animals were randomly assigned to be either orchidectomized or sham operated. Rats were killed 21 days after surgery, and comparisons were made in 12 anatomically matched sections of MPOA and 4 matched sections of diagonal band of Broca. In both studies, GnRH mRNA was quantitated by in situ hybridization, using a 35S-labeled oligodeoxynucleotide probe complementary to rat prepro-GnRH mRNA and a computerized image analysis system. In a third study, GnRH content was measured by RIA in microdissected regions of the arcuate nucleus and median eminence in intact 3- and 24-month-old male rats (n = 10 and 8, respectively). Serum LH, FSH, and testosterone (T) levels were measured by RIA in trunk blood of all animals. The number of neurons expressing the GnRH gene in the MPOA was significantly lower in sham-operated old rats (mean +/- SEM, 10.5 +/- 0.5 cells/section) than in young rats (13.7 +/- 0.7 cells/section; P less than 0.01), while cellular GnRH mRNA content was unchanged with age (103 +/- 1 vs. 103 +/- 2 grains/cell). Similar results were obtained in intact old and young rats. GnRH peptide content was significantly decreased in the arcuate nucleus of intact old (0.5 +/- 0.08 ng/mg protein) compared to young animals (2.3 +/- 0.7 ng/mg protein; P less than 0.05), with a trend toward a decrease in the median eminence of old (53 +/- 2 ng/mg protein) vs. young rats (69 +/- 7 ng/mg protein; P = 0.06).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935779 TI - Regulation of insulin-like growth factor-II production in bone cultures. AB - Although bone matrix is a rich source of insulin-like growth factor-II (IGF-II), little is known about the regulation of its synthesis by bone cells. This is due in part to the lack of simple and reliable assays to measure IGF-II. We have developed a method to dissociate IGF-II from its binding proteins by acidification and ultrafiltration, and quantitated IGF-II by RIA in 24- to 72-h cultures of 21-day-old fetal rat calvariae. The coefficient of variation of the assay was 13.8% or less; the recovery of IGF-II was 30-50%, and IGF-I cross reacted 1% or less in the assay compared to IGF-II standards. The IGF-II concentrations in calvarial culture medium were in the 1- to 3-nM range, and these levels were suppressed by cycloheximide (3.6 microM) by almost 80%. Continuous treatment with placental lactogen, PTH, GH, insulin, or T3 did not modify IGF-II concentrations in 24- to 72-h cultures. Treatment with 17 beta estradiol, testosterone, and 1,25-dihydroxyvitamin D3 also had no effect on IGF II levels, whereas cortisol (10-100 nM) decreased IGF-II concentrations by 20 50%. Transforming growth factor-beta, prostaglandin E2, and platelet-derived growth factor BB did not alter IGF-II levels, and basic fibroblast growth factor (0.06-6 nM) for 72 h decreased calvarial IGF-II by 30-50%. In conclusion, 21-day old fetal rat calvariae secrete IGF-II, and its concentration in culture medium is decreased by cortisol and basic fibroblast growth factor. PMID- 1935780 TI - Effect of recombinant activin-A on gonadotropin secretion in the female rat. AB - Repeated injections of recombinant human (rh) activin-A over a 2- to 3-day period are reportedly needed to stimulate the in vivo secretion of FSH. In this paper we present results showing that acute treatment with rh-activin-A caused marked and dose-dependent increases in plasma FSH, but not LH, levels in adult female rats. After one injection, maximum FSH release was observed 4 h after the administration of activin, while two injections of 100 micrograms activin/kg, 5 h apart, maintained elevated FSH levels for more than 10 h in intact diestrous day 1 females. Removal of the GnRH drive by pretreatment of ovariectomized animals with the GnRH antagonist ([Ac-D2Nal1,DCpa2,D3Pal3,Arg5,D-p-methoxyphenyl) 5- oxo 2-amino-pentanoic acid6, DAla10]GnRH; 100 micrograms/kg;) or repeated injections of the GnRH agonist ([DTrp6,Pro9,NEt,NH2]GnRH; 1 microgram/h for 5 days) did not prevent the stimulatory action of activin. Concomitant treatment with rh-inhibin A (30 micrograms/kg], on the other hand, completely blocked FSH secretion induced by 100 micrograms activin/kg. These results indicate that activin-A is a powerful stimulus for FSH secretion in the female rat and exerts this effect independently of GnRH. PMID- 1935781 TI - All major lung cancer cell types produce parathyroid hormone-like protein: heterogeneity assessed by high performance liquid chromatography. AB - We examined the production of parathyroid hormone-like protein (PLP) by all major lung cancer cell types, including epidermoid, small cell, and adenocarcinoma. We demonstrated that cell lines derived from each cell type released PLP into culture medium. To determine the predominant species of PLP produced by the cell lines, guanidine hydrochloride extracts were prepared and analyzed for PLP by high performance size exclusion chromatography under denaturing conditions. Cell lines from each of the major lung tumors produced multiple and different forms of PLP. The estimated molecular sizes of the PLP species ranged from 3.5-11.7 kilodaltons. Our results demonstrate that PLP is produced by all major lung cancer cell types and extend these observations to adenocarcinoma and large cell carcinomas of the lung. Furthermore, we observed PLP heterogeneity among these different cell types, which may represent tissue-specific PLP processing among different human lung tumors. PMID- 1935782 TI - Administration of growth hormone to pregnant rats on a reduced diet inhibits growth of their fetuses. AB - During gestation, female rats become resistant to the anabolic actions of GH. The importance of this resistance for conceptus growth was investigated by treating pregnant dams on a reduced diet with ovine (o) or bovine (b) GH during days 10-20 of gestation. Reducing food intake to 60% that of ad libitum-fed controls significantly depleted maternal inguinal fat stores by day 20 of gestation, but it did not affect the growth of the fetuses or the placentas. In the food restricted dams, twice daily injections of oGH (1 mg/day) or bGH (5 mg/day) during days 10-20 of gestation increased their inguinal fat pad wet weight by 28% and 62%, respectively, but had no effect on the wet weight of maternal heart, liver, or spleen. The dams treated with bGH had significantly heavier kidneys than the PBS- or oGH-treated females. On day 20 of gestation, control animals fed a 60%-diet had total serum insulin-like growth factor-I levels that were depressed to the same extent as those in ad libitum fed dams (i.e. to about 25% of the levels in nonpregnant females). Both the oGH and bGH treatments significantly elevated maternal serum insulin-like growth factor-I to 42% and 300%, respectively, of the levels in the untreated underfed dams. Compared to virgin controls, maternal tibial epiphyseal plate width was also significantly diminished in dams fed ad libitum or a 60% diet. Nevertheless, oGH and bGH were effective at augmenting maternal tibial epiphyseal plate width to equal those in virgin controls. Both doses of GH significantly reduced placental and fetal weights compared to those of PBS-injected dams on a 60% diet, and dams treated with the higher dose of GH were in an advanced stage of fetal and placental resorption by day 20 of gestation. Thus, maternal resistance to the anabolic actions of GH appears to be an important adaptation for diverting nutrients from the mother to the fetus. PMID- 1935783 TI - Calcitonin and calcitonin gene-related peptide are chemotactic for F9 embryonal carcinoma cells. AB - The chemotactic effect of calcitonin (CT) gene products was tested on F9 teratocarcinoma cells, which are an in vitro model of early embryonic development. CT and CT gene-related peptide (CGRP) induce a significant chemotactic response (chemotactic index, 40-50). The order of potency is: chicken CGRP greater than or equal to salmon CT greater than or equal to human CGRP. Human CT is a less potent chemotactic agent (chemotactic index, 15). Compared to other well known peptides with chemotactic activity, such as platelet-derived growth factor (no activity) and transforming growth factor-beta (chemotactic index, 5), CGRP and CT appear to be very active in attracting F9 cells in the Boyden chamber assay. Interestingly, CT and CGRP exhibit little chemotactic effect toward differentiated teratocarcinoma cells (i.e. retinoic acid-treated F9 cells or parietal endodermal PYS cells). While salmon CT and chicken CGRP activate adenylate cyclase activity in F9 cell membranes by 7- to 8-fold, higher concentrations (greater than 10(-10) M) of these peptides are required to stimulate cAMP formation than are required to mediate the chemotactic effect of these peptides. These data imply the possible involvement of CT gene products in regulating cell migration during early embryonic development. PMID- 1935784 TI - Effects of coculture of anterior and posterior pituitary cells on the responsiveness of lactotrophs to different secretagogues. AB - The synthesis and release of PRL are regulated by a variety of factors that originate in the hypothalamus, peripheral tissues, or posterior pituitary (PP). We recently reported that coculture of anterior pituitary (AP) and PP cells induced an increase in both PRL cell content and the responsiveness of lactotrophs to TRH. The aim of the present study was to determine whether the augmented response to TRH is due to increased lactotroph sensitivity to this particular secretagogue or to enhancement of the releasable pool of PRL. Cells obtained from anterior pituitaries of adult male rats were plated either alone or together with PP cells at the same total density. Cells cultures were maintained in serum-free medium for 4 days and then incubated for 20 min with the designated substances. Angiotensin-II and TRH evoked a significantly larger release of PRL in AP + PP cocultures than in AP cells cultured alone; the greatest difference between the culture types was observed at the highest concentrations of both secretagogues. The stimulation of PRL release by KCl, the calcium ionophore A23187, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate was higher in the presence of PP cells than in cultures of AP cells alone, although the magnitude of this effect was lower than that seen with PRL secretagogues. The concomitant application of A23187 and 12-O-tetradecanoylphorbol-13-acetate resulted in an increased response in both types of culture and a greater relative effect of PP cells on the evoked PRL release. In contrast to other secretagogues, oxytocin (OT) elicited a smaller response in AP + PP cocultures than in AP cultures. OT was present in significant amounts in medium from cocultures, apparently after being released from the severed neuronal terminals. When AP cultures were pretreated for 4 days with comparable concentrations of OT, the acute OT-evoked PRL release was greatly diminished. These findings suggest that coculture with PP cells increases the releasable pool of PRL in lactotrophs. The stored PRL is accessible for release by secretagogues known to act via the Ca2+ second messenger system, involving both Ca2+/calmodulin and protein kinase-C pathways. The diminished response of cocultures to OT is probably due to desensitization of lactotrophs by the residual amounts of this peptide present in the disrupted nerve endings. PMID- 1935785 TI - The contrasting role of calcium influx in secretion induced by cell swelling can differentiate normal and tumor-derived rat pituitary cells. AB - We have evaluated whether cell swelling may be a generally useful technique to differentiate normal and neoplastic pituitary cells, making the comparison between normal lactotrophs and thyrotrophs and tumor-derived GH4C1 and MMQ cells. With 1.5 mM medium Ca2+, cell swelling induced by osmotically equivalent stimuli, 27% medium hyposmolarity or 80 mM isotonic urea, caused a prompt increase in both intracellular Ca2+ and hormone secretion by all cell types. Depletion of medium Ca2+ abolished the cell swelling-induced increase in intracellular Ca2+ in all cell types and hormone secretion in the tumor-derived cells. However, it enhanced hormone secretion in normal cells. The critical role of Ca2+ influx in osmotically induced secretion in neoplastic, but not normal, pituitary cells may reflect some fundamental alteration in the intracellular transduction system in tumor cells. PMID- 1935786 TI - Inhibition of human breast cancer cell (MCF-7) growth in vitro by the somatostatin analog SMS 201-995: effects on cell cycle parameters and apoptotic cell death. AB - Somatostatin (SS) and SS analogs have been shown to exert an antiproliferative effect on several transplantable tumors in animals and to reduce the growth of pancreatic, pituitary, and mammary tumor cells in vitro. We evaluated the effects that the SS analog SMS 201-995 exerts on growth, cell-cycle parameters, and suicidal cell death (apoptosis) of human breast cancer cells (MCF-7) in vitro. SMS 201-995 significantly reduced the MCF-7 cell growth induced by serum, estradiol, insulin, and insulin-like growth Factor-I in both short term and long term experiments. The effect was maximal when 10 nM estradiol was used as mitogen in long term cultures. SMS 201-995 treatment produced a slight but transient accumulation of cells in the G2/M phase but did not cause any noteworthy reduction in the percentage of proliferating cells. There was, instead, a time related increase in the number of cells with the flow-cytometric characteristics of apoptosis in the cultures treated with the SS analog, which correlated well with its growth-inhibiting activity. It would, therefore, seem that SMS 201-995 exerts its inhibitory effect on MCF-7 cell growth in vitro mainly by enhancing the rate of programmed (or suicidal) cell death in the culture. PMID- 1935787 TI - Ontogenesis of the high affinity NADPH-dependent cytosolic 3,5,3'-triiodo-L thyronine-binding protein in rat. AB - Studies were undertaken to define the concentration of the high affinity NADPH dependent cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) in various tissues of adult rats and in those of developing rats. The maximal binding capacity (MBC) for T3 binding was calculated from the data obtained by Scatchard analysis of T3 binding to the charcoal-extracted cytosol in the presence of 50 microM NADPH. There were no significant differences in the affinity constant among various tissues, whereas the MBC was different among tissues in adult rats. When the levels of MBC were expressed by moles/DNA concentration, the order was as follows; kidney greater than heart greater than or equal to cerebrum greater than or equal to liver much greater than testis greater than cerebellum greater than spleen. The CTBP was not detected before birth in liver, heart, and spleen. The CTBP in these tissues emerged 5 days after the birth, and increased during 6 weeks after the birth. The CTBP in kidney was not detected before birth but was detected at the time of birth. The level of MBC in kidney increased during 3 weeks after the birth. In contrast, the CTBP was detected 5 days before birth, and the level of MBC increased at the time of birth both in cerebrum and cerebellum. The MBC in cerebrum gradually decreased after birth, but began to increase again 2 weeks after the birth. The level of MBC in cerebellum did not increase again. These results suggested that the target tissues of thyroid hormone are enriched with NADPH-dependent CTBP, and that the changes in the concentration of the CTBP are related to the growth of tissues. It was speculated that the CTBP has a specific function in cerebrum at the time of birth although the action of the CTBP is not certain. PMID- 1935788 TI - Levels of surfactant-associated protein messenger ribonucleic acids in rabbit lung during perinatal development and after hormonal treatment. AB - The levels of messenger RNAs for the surfactant-associated proteins, SP-A, SP-B, and SP-C, have been examined in the developing rabbit lung in vivo. Northern blot analysis detected SP-C mRNA by day 22 of gestation (term 31 days) and SP-A mRNA and SP-B mRNA on day 26, while solution hybridization assays detected all three mRNAs on day 22 of gestation. Both techniques revealed that the mRNA levels increased rapidly during the last quarter of gestation. The mRNA levels determined by solution hybridization were highly correlated during development, with average molar ratios of 1.0:1.1:2.1 for SP-A, SP-B, and SP-C, respectively. We also examined the effect of accelerating fetal pulmonary maturation by maternal administration of either 17 beta-estradiol or betamethasone (9 alpha fluoro-16 beta-methylprednisolone) on day 26 of gestation. These treatments increased SP-A mRNA levels 8- to 12-fold, resulting in levels 3- to 4-fold greater than in the adult. SP-B mRNA levels increased by approximately 2-fold to near adult levels, while SP-C mRNA was lowered somewhat by 17 beta-estradiol and significantly to less than half by betamethasone. No differences in the levels of surfactant apoprotein mRNAs or in choline incorporation into total or disaturated phosphatidylcholine were noted between male and female fetuses. These observations are consistent with the accepted view that the genes for the surfactant-associated proteins are independently regulated. However, the various factors affecting these mRNAs result in a coordination of mRNA levels during normal perinatal development. PMID- 1935789 TI - Sex differences in growth hormone (GH) secretion by rats administered GH releasing hexapeptide. AB - The purpose of this study was to compare GH secretion after the administration of GH-releasing hexapeptide (GHRP-6) in conscious male and female rats. Plasma GH was significantly elevated in female rats (six of six) compared to male rats (three of six) 15 min after administration of a single sc injection of GHRP-6 (0.5 mg/kg). In male rats, GHRP-6 administration was associated with suppression of episodic GH secretion and desensitization to a second injection administered 6 h later, whereas in female rats, GH secretion occurred after both GHRP-6 injections. After 14 consecutive days of administering GHRP-6 twice per day, mean plasma GH concentrations in males decreased from 110 +/- 91 to 2.8 +/- 0.6 ng/ml (P less than 0.05) and in females increased from 170 +/- 53 ng/ml to 361 +/- 81 ng/ml (P less than 0.05). Desensitization to GHRP-6 in conscious male rats was not observed in pentobarbital-anesthetized male rats, suggesting that GHRP-6 administration enhanced somatostatin release in the conscious state. After 14 consecutive days of GHRP-6 administration, the mean pituitary GH concentration in female rats was significantly lower than that in male rats (5.1 +/- 0.2 vs. 12.9 +/- 1.2 micrograms/mg, respectively). Lower pituitary GH concentrations in females correlated with higher GH secretion after GHRP-6 administration. Desensitization to GHRP-6 in male rats is attributed to neurohumoral factors producing their unusual pattern of episodic GH secretion, and the response is probably not typical of other species. PMID- 1935790 TI - Involvement of catecholamines in the effect of fasting on hepatic endothelial lipase activity in the rat. AB - The effect of fasting on hepatic endothelial lipase activity in the liver of adult rats was investigated. We found that, both in male and female rats, fasting produced a progressive decrease of the hepatic endothelial lipase activity. Upon refeeding, the activity returned to control values in 48 h. In isolated livers from fed male rats, a sharp peak of hepatic endothelial lipase activity appeared in the perfusate upon heparin addition. It accounted for 75% of the total activity (heparin-released + residual) of the tissue. Fasting (24 h) decreased the heparin-releasable activity, and this effect was responsible for most of the decrease found in whole tissue. We suggest that the effect might be due to a decreased synthesis and/or secretion of the enzyme by hepatocytes, since isolated hepatocytes from fasted rats, incubated at 37 C, released 65% less activity to the incubation medium than hepatocytes from fed rats. Adrenaline, but not insulin, glucagon, dexamethasone, epidermal growth factor, or T3, decreased the amount of hepatic endothelial lipase activity released by hepatocytes isolated from fed rats. The effect of adrenaline appears to be mediated by alpha 1 receptors since phenylephrine but not isoprenaline reproduced, and prazosin but not propranolol blocked, the effect of the catecholamine. In the presence of cycloheximide, adrenaline also decreased the amount of activity released. We suggest that, in our incubation conditions (up to 3 h), the hormone affects the posttranslational processing of the enzyme. In vivo administration of prazosin blocked the effect of both noradrenaline and fasting on hepatic endothelial lipase activity in whole liver. Those results suggest that catecholamines are involved in the decreased hepatic endothelial lipase activity found in the liver of fasted rats, and points out the role of these hormones in the acute modulation of an enzyme involved in reverse cholesterol transport. PMID- 1935791 TI - The effects of endothelins on the secretion of prolactin, luteinizing hormone, and follicle-stimulating hormone are mediated by different guanine nucleotide binding proteins. AB - Different bacterial toxins capable of modifying specific alpha-subunits of G proteins were used to characterize the guanine nucleotide-binding protein (G protein) dependency of the effects of endothelins (ETs) on PRL, LH, and FSH secretion. Primary cultures of anterior pituitary cells obtained from female rats were preincubated for 24 h with 20 ng/ml pertussis toxin (PTX) or 2 micrograms/ml cholera toxin (CTX) before challenge with ETs. Both ET-1 and ET-3 elicited a concentration-dependent inhibition of PRL secretion and stimulated the release of LH and FSH secretion on pituitary cells not treated with toxins. Based on the calculated ration of the half-maximal effective concentrations (EC50) of ET-1 and ET-3, ET-1 showed 7800, 20, and 14 times greater potency than ET-3 on PRL, LH, and FSH secretion, respectively. PTX, a selective inhibitor of Gi and several other G proteins, increased the basal secretion of PRL and completely eliminated the responsiveness of lactotroph cells to ET-1 and ET-3. Pretreatment with PTX caused a markedly different effect on LH and FSH secretion: while basal LH release was slightly increased, FSH secretion was markedly depressed by PTX. Moreover, while ET-induced LH secretion was enhanced by PTX, the effectiveness of ETs on FSH release was completely abolished. CTX, known as an activator of Gs proteins, decreased the basal secretory activity of lactotrophs but did not influence the ET-induced decrease of PRL release. CTX pretreatment (like PTX before) elicited a strikingly different effect on LH and FSH: while basal LH secretion was enhanced, basal FSH secretion was markedly inhibited by CTX. Moreover, while the effectiveness of ETs on LH secretion was not changed significantly, the stimulatory effect of ETs on FSH secretion was diminished after CTX pretreatment. Thus, the inhibition of PRL secretion by ETs requires a PTX-sensitive G protein while the ET-induced stimulation of FSH secretion involves both PTX- and CTX-sensitive elements. The fact that pretreatments with PTX or CTX influenced basal secretion of PRL, LH, and FSH suggests that PTX- and/or CTX-sensitive G proteins are directly involved in the process of exocytosis. Additionally, these findings might indicate an active paracrine/autocrine regulation of pituitary cells in culture that are impaired or enhanced by the bacterial toxins employed. Though the broad substrate specificity of PTX and CTX and the multiplicity of G protein families did not allow us to identify the specific G protein(s) involved, these data reveal the diversity of ET-induced intracellular signaling mechanisms in lactotrophs and gonadotrophs. PMID- 1935792 TI - Comparative in vitro and in vivo studies on the biological characteristics of recombinant human follicle-stimulating hormone. AB - The in vitro and in vivo activities of recombinant human FSH (recFSH) produced by a Chinese hamster ovary cell line were studied and compared with those of natural FSH preparations. The specific FSH activities of recFSH established by immunoassay and in vivo bioassay were greater than 10,000 IU/mg protein and considerably higher than the activities of tested urinary FSH references, while the in vivo bio/immuno ratios of these preparations were not significantly different. Compared to a highly purified pituitary standard (IS 83/575), recFSH had a comparable high specific in vivo bioactivity, but the specific immunoreactivity of IS 83/575 was about 2 times lower. In receptor displacement and in vitro bioassay studies recFSH provided dose-response curves parallel to those of pituitary and urinary FSH references. When equal amounts of immunoreactivity FSH were tested, recFSH and urinary and pituitary FSH displayed comparable activities in both assays. The in vitro bioactivity of recFSH could be neutralized effectively by each of three monoclonal antibodies raised against recFSH (alpha-specific), urinary FSH (beta-specific), and pituitary FSH (alpha beta-specific), respectively. Moreover, 50% inhibition of comparable responses induced by recFSH, urinary "pure" FSH, or pituitary FSH was established by the same amount of monoclonal antibody. These results support the structural and functional similarity of recFSH and natural FSH. To test whether recFSH is capable of inducing LH-specific biological responses, the in vitro induction of testosterone production in mouse Leydig cells was assessed. At least 16 IU recFSH/ml incubate were needed to increase testosterone production, indicating that the intrinsic LH bioactivity of recFSH is negligible (less than 0.025 mIU LH/IU FSH). The in vivo efficacy of recFSH was examined by treating immature female hypophysectomized rats during 4 days with recFSH only or with recFSH supplemented with hCG. RecFSH only treatment increased ovarian weight and aromatase activity in a dose-dependent manner. When recFSH dosages providing submaximal responses were supplemented with 1 IU hCG, both ovarian weight and aromatase activity were largely augmented. Neither recFSH nor urinary pure FSH, administered in a high dose was able to increase plasma estradiol levels, while ovarian weight and aromatase activity were increased to the same extent. However, when recFSH was supplemented with only 0.1 IU hCG, a 3-fold increase in median plasma estradiol levels was obtained. These findings support the two-cell two gonadotropin theory, holding that both FSH and LH are required for estrogen biosynthesis, but also reveal that only very small amounts of LH activity are sufficient to increase estrogen secretion up to measurable plasma levels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935793 TI - Characterization of the microheterogeneity of recombinant primate prolactin: implications for posttranslational modifications of the hormone in vivo. AB - Recombinant baboon and monkey prolactins were expressed in murine C127 cells. The hormones were purified from the conditioned media of these cells using a combination of cation, anion, and gel filtration chromatographies. This purification scheme provided approximately a 20-fold purification of the proteins with a 40% cumulative yield. Sodium dodecyl sulfate gel electrophoresis of the purified hormones in conjunction with Coomassie blue staining and immunoblotting procedures revealed three major prolactin-related bands with molecular weights corresponding to Mr 16,000, 23,000, and 27,000. Based on these analyses the samples were judged to be greater than 90% pure. Amino terminal sequence analysis of the purified baboon and monkey hormones provided three distinct prolactin related sequences for each preparation. The predominant sequence corresponded to the predicted amino terminal sequences of the hormones which began with leucine at position 1. Two minor sequences, individually representing approximately 10 20% of the total population, were also identified; one starting at position 11 and the other at position 133. Carbohydrate compositional analysis of the proteins suggested that greater than 50% of the population were glycosylated with a fucosylated complex oligosaccharide. Analysis of the specific bioactivity of the recombinant hormones in the Nb2 cell proliferation assay showed them to be comparable to the NIH and WHO human pituitary-derived standards. PMID- 1935794 TI - Cyclosporin-mediated depression of luteinizing hormone receptors and heme biosynthesis in rat testes: a possible mechanism for decrease in serum testosterone. AB - The toxic side-effects of the immunosuppressive drug cyclosporin (CsA) include testicular dysfunction and a decline in circulating testosterone. However, mechanisms for the consistently observed CsA-mediated depression of serum testosterone levels are unclear because of conflicting reports concerning circulating gonadotropin levels and incomplete studies of intratesticular steroidogenesis. To elucidate these mechanisms, endocrine-regulated testicular steroidogenesis and heme metabolic parameters were studied in male rats given sc injections of either 25 or 40 mg/kg.day CsA for 6 days and then killed on the seventh day. Consistent with earlier reports, CsA treatment dramatically suppressed serum testosterone levels (less than 20% of control at both CsA doses). Additionally, the intratesticular testosterone content declined with the higher CsA dose. Serum LH and FSH levels were elevated up to 2- to 4-fold after the higher CsA treatment regimen. Measurement of decreases in testicular receptors for LH revealed for the first time that CsA treatment significantly reduced the ability of the testes to respond to normal or elevated circulating levels of LH. In animals receiving higher dose of the drug, cytochrome P-450 dependent mitochondrial cholesterol side-chain cleavage activity, which is the rate-limiting step in steroidogenesis, was markedly reduced to a mere 30% of the control value. Additionally, the activity of the microsomal cytochrome P-450 dependent 17 alpha-hydroxylase was decreased to less than half of the control value. Biotransformation of the prototype drug, benzo(a)pyrene, as well as microsomal cytochrome P450 levels declined significantly after the higher CsA dose, suggesting that CsA has an adverse affect on testicular cytochromes P-450 in general. In addition, CsA treatment altered heme metabolic parameters; significant increases in the activity of uroporphyrinogen-I synthetase and total porphyrin content were noted. Conversely, the activity of ferrochelatase, the enzyme that incorporates iron into porphyrin to form heme molecule, decreased significantly, as did the total heme levels. The latter was reduced to only 61% of control values. The findings suggest the likelihood that the observed inhibition of heme formation may contribute substantially to the reduced levels of microsomal cytochromes P-450 and steroidogenic activities that depend on them. Taken collectively, these data suggest a plausible mechanism by which CsA may induce testicular dysfunction; as the result of a combination of reduction in the number of LH receptors and a suppression of heme formation, the hemoprotein dependent steroidogenic enzymes activities are compromised, leading to an impairment of normal testicular function. PMID- 1935795 TI - Outer ring iodothyronine deiodinases and thyroid hormone economy: responses to iodine deficiency in the rat fetus and neonate. AB - Female rats were fed a low iodine diet (LID) or the same diet supplemented with KI (IOD) and mated. Plasma TSH, T4 and T3 in thyroid, plasma, and tissues, and 5' deiodinase activities (5'D) were measured in maternal, fetal, and neonatal samples. Plasma T4 was markedly reduced in LID dams, TSH was increased, and T3 was normal. Placental T4 was decreased to 10%, and placental T3 to 50%. In LID fetuses there was a complete depletion of both extrathyroidal and intrathyroidal stores of T4 and T3. The thyroid responded with increased synthesis and secretion of T3 over T4, as assessed from the T3 to T4 ratios. Near birth, brain T4 and T3 concentrations were only 6.7% and 12% of those in IOD fetuses, despite a marked increase in brain 5'D-II and a T4-sparing decrease in liver and lung 5'D-I. Brown adipose tissue 5'D-II increased 7-fold, and brown adipose tissue T4 and T3 concentrations were only decreased by 50%. After birth, the availability of iodine improved somewhat through maternal milk, and the thyroidal and extrathyroidal pools of T4 and T3 increased, although they remained much lower than those in IOD pups. Brain 5'D-II markedly increased in LID pups, and this together with an increase in plasma and brain T4 ensured almost normal brain T3 during the suckling period. The thyroidal secretion of T3 over T4 continued to be increased in LID pups during the suckling period and appeared to be related to their high circulating TSH levels. Both LID fetuses and newborns can respond to iodine deficiency as adults rats, but the fetus is more sensitive to LID because of its dependence on maternal T4. The success of the adaptative mechanisms in protecting the brain from severe T3 deficiency depends on the supply of iodine, the limiting factor for the synthesis of T4. PMID- 1935797 TI - Ontogenesis of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in the rat adrenal as revealed by immunocytochemistry and in situ hybridization. AB - The enzyme 3 beta-hydroxy-5-ene-steroid dehydrogenase/5-ene-4-ene isomerase (3 beta-HSD) catalyzes an essential step in the biosynthesis of all classes of active steroids, namely glucocorticoids, mineralocorticoids, progesterone, and sex steroids. To obtain further information on the expression and localization of 3 beta-HSD during development in the rat adrenal, two complementary cytochemical techniques were used: immunocytochemical localization with antibodies against purified human placental 3 beta-HSD, and 3 beta-HSD messenger RNA localization achieved by in situ hybridization with a rat 3 beta-HSD complementary DNA probe. During foetal development, the first detection of 3 beta-HSD messenger RNA was achieved on day 16 by in situ hybridization, the silver grains being located on the cortical cells. Between days 17 and 20, on the other hand, immunostaining became positive in the cytoplasm of the same cortical cells, the capsule being negative by both immunostaining and in situ hybridization. Interestingly, two distinct zones of intensity of 3 beta-HSD localization could be distinguished, namely the highly labeled reticular and fascicular zones and the less positive glomerular zone. This observation coincides with the onset of fetal ACTH secretion on days 17-18 and with accelerated adrenocortical growth and differentiation. After birth and until day 25, strong immunolabeling was observed in the cytoplasm of adrenocortical cells, the glomerular zone being labeled at a lower degree than the remaining cortex. The same localization was obtained by in situ hybridization. This low labeling of the glomerular zone might be related to the low plasma levels of angiotensin II observed in the immature rat. From day 25 after birth, the three zones of the cortex were uniformly labeled and no immunostaining was seen in the medulla or capsule. Similarly, by in situ hybridization, silver grains were located exclusively in the adrenal cortex. The present data suggest that 3 beta-HSD expression could well play a major role in regulating adrenal function during foetal and postnatal development. PMID- 1935796 TI - Increased synthase phosphatase activity is responsible for the super-activation of glycogen synthase in hepatocytes from fasted obese Zucker rats. AB - Addition of 60 mM glucose caused a similar partial activation of glycogen synthase in hepatocytes isolated from overnight fasted Wistar rats and from fasted lean Zucker (Fa/fa?) rats. In contrast, the activation went rapidly to completion in cells from fasted obese (fa/fa) rats. Subsequent addition of 4 microM microcystin, a potent inhibitor of type 1 and type 2A protein phosphatases, induced a rapid inactivation of glycogen synthase, which occurred at a similar rate in all three types of hepatocytes. This suggests that the super activation of glycogen synthase in hepatocytes from fasted obese rats is not due to a lower synthase kinase activity. Glycogen synthase phosphatase was quantitatively assayed in broken-cell preparations from the same livers, with exogenous synthase b as substrate. The synthase phosphatase activity in the fa/fa livers was 3-fold higher than that in the livers from both lean Zucker rats and Wistar rats. This difference has to be attributed to an increased synthase phosphatase activity of the glycogen-bound protein phosphatase-1 in livers of fasted obese rats. The results suggest that in the latter animals the available insulin exceeds the insulin resistance of the liver. The resulting overexpression of the insulin-dependent synthase-phosphatase-1G activity may explain the super activation of glycogen synthase in response to a glucose challenge. PMID- 1935798 TI - Cortisol modulates the actions of interleukin-1 alpha on bone formation, resorption, and prostaglandin production in cultured mouse parietal bones. AB - Previous studies have shown that both interleukin-1 (IL-1) and glucocorticoids inhibit collagen synthesis in bone organ and cell cultures. In this study we examined their interactions in cultured neonatal mouse parietal bones. IL-1 alpha stimulated [3H]thymidine incorporation. Cortisol decreased thymidine incorporation, but did not block the effect of IL-1. Both cortisol and IL-1 alpha decreased the incorporation of [3H]proline into collagenase-digestible protein (CDP) and reduced alpha 1(I)procollagen mRNA levels at 72 h. Noncollagen protein (NCP) labeling was increased by IL-1 and decreased by cortisol. In the presence of cortisol, IL-1 alpha (6 pM) increased CDP as well as NCP labeling. The increase in CDP labeling was paralleled by an increase in alpha 1(I)procollagen mRNA, suggesting a pretranslational site for the cortisol-IL-1 alpha interaction. In the same bones, cortisol consistently blocked IL-1 alpha-stimulated 45Ca release and prostaglandin E2 (PGE2) production. The ability of IL-1 alpha to increase CDP in the presence of cortisol was the same in the presence or absence of indomethacin, an inhibitor of PGE2 synthesis, or aphidicholin (30 microM), an inhibitor of DNA synthesis, indicating that the reversal was neither PG mediated nor dependent on cell proliferation. In conclusion, our results demonstrate that IL-1 inhibits collagen, but not NCP or DNA, synthesis and that cortisol inhibits IL-1 alpha-induced bone resorption and PGE2 production and reverses its inhibitory effect on collagen synthesis in cultured neonatal mouse calvariae. PMID- 1935799 TI - Stimulation of prolactin cell differentiation in vitro by a milk-borne peptide. AB - We have previously reported that the normal expression of PRL-secreting cells in neonatal rats requires a maternal signal specific to the first few days of lactation. These results raised the possibility that a milk-borne factor(s) ingested by the neonate and absorbed into the circulation might induce the ontogenic appearance of PRL cells. The purpose of the present study was to determine whether milk from this period could directly stimulate the differentiation of PRL secretors in culture. Monodispersed anterior pituitary cells from 1-day-old pups were cultured for 6 days with aqueous extracts of milk from early (days 2, 3, and 4) and late (days 15 and 16) lactation and then subjected to reverse hemolytic plaque assays for PRL and GH release. We found that the addition of milk extracts (10 mg/ml) from either early or late lactation stimulated the differentiation of PRL secretors (to 6.1 +/- 1.0% and 2.4 +/- 0.7% of all pituitary cells, respectively; mean +/- SE; n = 3) above that in control cultures without milk (0.2 +/- 0.2%). Thus, early milk was more than twice as effective as late milk in this regard (P less than 0.05). This effect appeared to be specific to PRL cell differentiation, since the relative abundance of GH secretors was not different between cells treated with either early or late milk (29.3 +/- 4.8% and 33.7 +/- 3.9%, respectively). On the other hand, late milk was more than twice as effective as early milk at increasing the capacity of GH secretors to release hormone (P less than 0.05). Preliminary characterization by gel filtration chromatography and proteolytic hydrolysis indicates that the bioactivity that differentiates PRL secretors is a small peptide(s) of 2000-6000 daltons. Taken together, our results demonstrate that a milk-borne peptide(s) is capable of specifically stimulating the differentiation of PRL-secreting cells in vitro, and that this bioactivity is more prevalent in milk from early lactation. PMID- 1935800 TI - Inhibition of hypothalamic thyrotropin-releasing hormone messenger ribonucleic acid during food deprivation. AB - Food deprivation in laboratory rats induces profound changes in the neuroendocrine system. We have investigated the hypothalamic and pituitary responses of the hypothalamo-pituitary thyroid axis to 48-h food deprivation in Sprague-Dawley rats. Peripheral T3 and hypophysial portal TRH were measured by RIA, and TSH beta, PRL, and pro-TRH mRNA were measured using in situ hybridization histochemistry. Peripheral total T3 was greatly reduced in food deprived rats. Hypothalamic portal blood TRH levels declined significantly with time in control animals. The initial level of TRH in the portal blood of food deprived rats was significantly reduced compared to that in controls, but did not fall further with time. In situ hybridization histochemistry revealed significantly lower pro-TRH mRNA in the paraventricular nucleus of food-deprived animals, while pro-TRH mRNA in the reticular nucleus remained unaltered. Furthermore, in the anterior pituitary, TSH beta mRNA decreased significantly in food-deprived animals, while PRL mRNA was unaltered. We conclude that the reduction in circulating T3 after food deprivation appears to be due primarily to decreased hypothalamic TRH synthesis and release. PMID- 1935801 TI - Cell cycle phase dependence of estrogen and epidermal growth factor (EGF) receptor expression in MCF-7 cells: implications in antiestrogen and EGF cell responsiveness. AB - In this report the effect of epidermal growth factor (EGF) and the antiestrogen hydroxytamoxifen (OH-TAM) on the cell cycle of the breast cancer cell line MCF-7 was investigated as a function of the presence of their respective receptors. For this study synchronized cells were obtained by cell incubation in the presence of 2 mM thymidine for 24 h at 37 C. The treatment led to a partial synchronization, since at the end of thymidine treatment, 80% of cells were accumulated in the G1 phase. The removal of thymidine allowed the cells to progress through the cell cycle, since between 6-9 h after the arrest of the treatment, about 50% of cells were found in the S phase. By 9-12 h, most of the cells entered the G2 phase, and by 24 h, the cells returned to the G1 phase. When MCF-7 cells were incubated in the presence of OH-TAM for various periods of time before thymidine exposure, the progression of the cells through the cell cycle was dramatically inhibited. Also, a short term antiestrogen treatment (2 h) before or immediately after the addition of thymidine led to an accumulation of MCF-7 cells in the G1 phase. However, when the cells were treated for 2 h with OH-TAM 22 h after thymidine addition or shortly after its removal from the cell culture, no effect of the antiestrogen on the cell cycle could be observed. In parallel, the effect of thymidine on the level of estrogen receptor was studied. Although low affinity estrogen-binding sites were maintained, high affinity ER were found to be dramatically reduced during the thymidine treatment. The comparison between the effect of OH-TAM on the cell cycle and the expression of ER revealed that the antiestrogen OH-TAM was effective only in the presence of ER. EGF was found to have no effect on the cell cycle of thymidine-synchronized cells, although it did partially reverse the G1 phase block induced by OH-TAM when added simultaneously to cell culture 24 h before thymidine exposure. The parallel analysis of EGF receptor level demonstrated that thymidine treatment also reduced EGF receptors that were found to reappear after the synchronization, during the S and G2 phases of the cell cycle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935802 TI - Angiotensin II receptor and postreceptor events in adrenal glomerulosa cells from streptozotocin-induced diabetic rats with hypoaldosteronism. AB - Streptozotocin-induced chronic diabetic rats develop hyporeninemic hypoaldosteronism. The hypoaldosteronism is associated with selective unresponsiveness of aldosterone to angiotensin II (AII) and an atrophy of the zona glomerulosa. To assess the nature of the adrenal unresponsiveness to AII, we examined the [125I]monoiodoAII binding and the responses of pregnenolone formation and aldosterone production to AII using adrenal glomerulosa cells from diabetic rats 6 weeks after an injection of streptozotocin. Comparisons were made using the cells from control rats treated with vehicle. Diabetic rats had low levels of plasma renin activity, plasma 18-hydroxycorticosterone, and plasma aldosterone, and normal levels of plasma corticosterone and plasma potassium. The zona glomerulosa width was narrower in diabetic than in control rats. Scatchard analysis of the AII binding data demonstrated that the number and affinity of the receptors were similar in the cells from control and diabetic rats. When corrected to an uniform number of cells per group, baseline levels of pregnenolone formation and aldosterone production were similar in the cells from control and diabetic rats. However, cells from diabetic rats had a less sensitive and lower response of both pregnenolone formation and aldosterone production to AII. In contrast, the effect of ACTH on pregnenolone formation and aldosterone production was similar in the cells from control and diabetic rats. These results indicate that the main defect responsible for the hypoaldosteronism may be located on some step(s) mediating between AII receptors and conversion of cholesterol to pregnenolone, presumably on the calcium messenger system, with a disturbance downstream from AII binding. PMID- 1935803 TI - Glucose regulation of growth hormone receptors in primary cultured rat hepatocytes. AB - The effects of nutritional factors on the regulation of GH receptors were studied by measuring the specific binding of 125I-human GH to rat hepatocytes cultured in various media. The binding of labeled GH to primary cultured hepatocytes decreased during culture, the extent of the decrease depending on the culture medium. The decreases of GH binding during culture in glucose-poor media (i.e. Williams' medium E, Dulbecco's modified minimum essential medium, and McCoy 5A medium) were significantly more than that in glucose-rich Waymouth's medium MB 752/1 (Waymouth's). In glucose-poor media supplemented with glucose, the extent of decrease of GH binding was comparable to that in Waymouth's. Other hexoses such as D-fructose and D-mannose also significantly reduced the decrease in GH binding. Scatchard plot analysis showed that the effect of glucose in preventing decrease of GH binding was due to change in the number of binding sites without significant change in their affinity. The effect of glucose was additive with that of dexamethasone, which induces GH receptors. Cycloheximide caused almost complete loss of GH binding by cells cultured in the presence of glucose. 2 Deoxyglucose reduced the effect of glucose, but did not affect that of dexamethasone. These results show that glucose counteracts decrease of GH binding sites during culture and suggest that it affects de novo synthesis of GH receptors, presumably through glycosylation of a certain protein that regulates GH receptor gene expression (new protein synthesis). The mechanism of the effect of glucose on induction of GH receptors seems to be different from that of dexamethasone. PMID- 1935804 TI - Molecular cloning and expression of rat placental lactogen-Iv, a variant of rPL-I present in late pregnant rat placenta. AB - Late pregnant rat placenta was found to contain a messenger RNA (mRNA) that encodes an additional member of the prolactin-growth hormone family. This polypeptide was detected by hybridization of complementary DNA (cDNA) for rPL-I to a 1 kilobase mRNA transcript in late pregnant rat placenta. A cDNA clone for the new polypeptide was isolated from a phage lambda-gt10 library containing cDNA synthesized from day 18 rat placental mRNA. Sequencing of the day 18 cDNA clone revealed that it was most closely related structurally to rPL-I and at the amino acid terminal was identical to the rPL-I variant (rPL-Iv). The sequence of rPL-Iv (223 amino acids) is 85% homologous to rPL-I (230 amino acid). There are 71 base pair changes (85% nucleotide homology) between rPL-Iv and rPL-I which are not confined to any specific region of the molecule and which result in 36 amino acid changes. In vitro translation of rPL-Iv mRNA produced by transcription of the cDNA template yielded a 26 kilodalton polypeptide, the size of the expected precursor protein. In situ hybridization studies indicated that mRNA for rPL-Iv was present primarily in cytotrophoblasts of the basal zone as early as day 15 of gestation with some hybridization in a few giant cells as well. PMID- 1935805 TI - Contact-dependent intercellular communication of bovine luteal cells in culture. AB - Mammalian gap junctions permit exchange of nutrients, ions, and regulatory molecules of less than 1.5 kDa among contacting communication-competent cells and may be important for regulation of luteal function and maintenance of luteal homeostasis. The present studies were designed to evaluate gap junction-mediated intercellular communication between bovine luteal cells in culture. Using a dye coupling technique along with interactive laser cytometry, selected luteal cells were studied for the rate of contact-dependent fluorescence redistribution after photobleaching. The rate of communication, reported as the rate of fluorescence recovery (percentage per min), was determined for steroidogenic cells as follows: 1) small luteal cells contacting only small luteal cells, 2) large luteal cells contacting only small luteal cells, and 3) large luteal cells contacting only large luteal cells. In addition, the effects of known regulators of luteal function [LH, prostaglandin F2 alpha (PGF), and forskolin] on the rate of intercellular communication were determined. Small luteal cells communicated rapidly with each other, exhibiting an initial rate of fluorescence recovery of 4.1 +/- 0.1%/min (n = 187). The rate of small cell-small cell communication was unaffected by LH and PGF. For large luteal cells contacting small luteal cells, however, LH and PGF stimulated (P less than 0.02) the rate of communication compared with no hormone [1.6 +/- 0.2 (n = 18) and 1.5 +/- 0.6 (n = 20) vs. 0.8 +/- 0.3%/min (n = 27), respectively]. LH and PGF in combination, however, did not enhance the rate (0.6 +/- 0.2%/min; n = 19) of large cell-small cell communication. In contrast, forskolin significantly stimulated both small cell small cell and large cell-small cell communication rates compared with no forskolin [34% increase (n = 48) and 50% increase (n = 23), respectively]. Large luteal cells did not communicate with each other under any condition tested. Transmission electron microscopy revealed the presence of numerous gap junction like structures in bovine luteal cells in culture. These data suggest that luteal cells are capable of intercellular communication and that the rate of communication may be influenced by hormones. Contact-dependent intercellular communication among luteal cells may, therefore, play a significant role in the regulation of luteal function. PMID- 1935806 TI - Triiodothyronine receptor beta-2 messenger ribonucleic acid expression by somatotropes and thyrotropes: effect of propylthiouracil-induced hypothyroidism in rats. AB - mRNA for a thyroid hormone receptor isoform that is unique to the pituitary gland (TR beta-2) is down-regulated by T3. Increases in the expression of this mRNA are seen in rats rendered hypothyroid by treatment with propylthiouracil (PTU). This study used dual labeling to determine which pituitary cells expressed TR beta-2 mRNA in normal and PTU-treated rats. In situ hybridization protocols localized the mRNA (with biotinylated complementary oligonucleotide probes detected by avidin-biotin-peroxidase), and immunoperoxidase protocols identified the pituitary hormone proteins. In dispersed pituitary cells, 20 +/- 2% (average +/- SD) of cells from normal rats and 30 +/- 3% of cells from PTU-treated rats were labeled for TR beta-2 mRNA. PTU caused increases in the area of the labeled cells (from 114 +/- 11 to 225 +/- 7 microns 2), the area of the label per cell (from 27 +/- 3 to 71 +/- 11 microns 2), and label density. PTU produced increases in the percentage of TSH cells from 8 +/- 1% to 19 +/- 2%, decreases in the percentage of GH cells from 27 +/- 3% to 11 +/- 2%, and no change in other cell types. After dual labeling, 73% of cells that expressed TR beta-2 mRNA stored either TSH (35 +/- 8) or GH (38 +/- 6). Less than 10% stored other hormones. When each cell type was analyzed, 56 +/- 3% of TSH cells and 43 +/- 4% of GH cells expressed TR beta 2 mRNA. When these percentages were multiplied by the percentages of each cell type in the overall population, TSH and GH cells with TR beta-2 mRNA represented 6.8 +/- 1% and 11.6 +/- 1% of the pituitary cells, respectively. Less than 1% of all pituitary cells expressed TR beta-2 and ACTH (0.9 +/- 0.06), LH (0.8 +/- 0.1), FSH (0.8 +/- 0.1), and PRL (0.9 +/- 0.04). PTU treatment increased the percentage of TSH cells with TR beta-2 mRNA to 72 +/- 4% and decreased the percentage of GH cells with TR beta-2 mRNA to 30 +/- 3%. However, some enlarged putative TSH cells could not be identified by immunolabel because the storage levels were low. Thus, changes in TR beta-2 mRNA in hypothyroid rats may be the net result of the increase in the percentage of TSH cells, the amount of mRNA per cell (measured by area and density of label), and the decrease in the percentage of GH cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935807 TI - Transcriptional regulation of the production of the third component of complement (C3) by 1 alpha,25-dihydroxyvitamin D3 in mouse marrow-derived stromal cells (ST2) and primary osteoblastic cells. AB - We have purified a 190-kDa protein produced by mouse marrow-derived stromal cells (ST2) in response to 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] and unequivocally identified it as mouse complement C3 (C3). In this study we examined the regulation by 1 alpha,25-(OH)2D3 of C3 production in ST2 cells at both the transcriptional and translational levels. 1 alpha,25-(OH)2D3 greatly increased the protein production of C3 at 24 h, and it attained a maximum at 72 h. C3 mRNA stimulation by 1 alpha,25-(OH)2D3 was initiated at 12 h and reached a maximum at 48 h. 1 alpha,25-(OH)2D3 increased the expression of C3 mRNA dose dependently, ranging from 10(-10)-10(-8) M. The increase in the C3 production in response to 1 alpha,25-(OH)2D3 appeared to occur at a transcriptional level, since actinomycin-D completely inhibited both mRNA expression and protein production of C3 induced by 1 alpha,25-(OH)2D3. Besides 1 alpha,25-(OH)2D3, local bone-resorbing agents, such as interleukin-1 alpha, tumor necrosis factor-alpha, and lipopolysaccharides, also stimulated the expression of C3 mRNA, not only in ST2 cells, but also in primary osteoblastic cells. C3 production by hepatocytes occurred regardless of the presence or absence of 1 alpha,25-(OH)2D3. These results clearly indicate that 1 alpha,25-(OH)2D3 tissue-specifically regulates the synthesis of C3 in bone. Bone C3 may play an important role in bone metabolism. PMID- 1935808 TI - Immunocytochemical localization of protein kinase-C subtypes in anterior pituitary cells: colocalization in hormone-containing cells reveals heterogeneity. AB - We have examined the distribution and colocalization of protein kinase-C (PKC) in cultured rat anterior pituitary cells by light microscopic immunocytochemistry using monoclonal antibodies to group A rat brain PKC subspecies. Type I (PKC gamma) was not detected in the cells, in line with the assertion that the gamma enzyme is expressed specifically in central nervous tissues. The other subspecies recognized by the antibodies (PKC beta and PKC alpha) were present throughout the cytoplasm in a diffused pattern, while the nuclei were apparently unstained. The number of cells stained with the antibodies in juvenile animals (12 days old) increased rapidly with age and reached a plateau between adult (5-month-old) and older (1-yr-old) rats. Type II (PKC beta) was the predominant subspecies detected in anterior pituitary cells. Double immunofluorescence staining techniques enabled the colocalization of PKC with various anterior pituitary cell types. Surprisingly, not all of the hormone-producing cells were stained with the PKC antibodies. Moreover, within the different pituitary cell types, the percentage of PKC-stained cells varied, revealing heterogeneity among the various cell populations. Thus, among somatrophs, mammotrophs, thyrotrophs, ACTH-containing cells, and gonadotrophs, only 9%, 22%, 13%, 44%, and 26%, respectively, reacted with the PKC antibodies. We suggest that activation of pituitary PKC might mobilize only a fraction of the hormone-containing cells. PMID- 1935809 TI - Tissue distribution of PACAP as determined by RIA: highly abundant in the rat brain and testes. AB - A heterologous RIA method for pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38) and a homologous RIA method for a shorter form of PACAP with 27 residues (PACAP27) were established to determine PACAP content in central and peripheral tissues in rats. The highest concentration of radioimmunoassayable PACAP38 was found in the hypothalamus, but other brain regions also contained considerable amounts of PACAP38. PACAP38 concentration in the posterior pituitary was comparable with that in the extrahypothalamic brain, but its concentration in the anterior pituitary was very low. Unexpectedly, the testis contained a high abundance of PACAP38, and the total amount of PACAP in both testes exceeded its content in the whole brain. Reverse phase HPLC suggested that the major testicular PACAP38 immunoreactivity represents PACAP38. Among peripheral tissues, adrenal gland contained the second highest concentration of PACAP. Smaller amounts of PACAP were widely distributed in the digestive tract and other peripheral tissues. The concentration of PACAP in stomach, duodenum and jejunum appeared to be greater than in other portions of the gut. In all tissues, PACAP27 represented only a minor portion of total PACAP immunoreactivity. PMID- 1935810 TI - A novel mechanism for the induction of aromatase in ovarian cells in vitro: role of transforming growth factor alpha-induced protein tyrosine kinase. AB - In the developing follicle, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are the primary stimulators of steroidogenesis in granulosa and theca cells. The steroidogenic actions of both these gonadotropins are largely if not exclusively mediated through cAMP. Previous studies have shown that EGF and TGF alpha do not affect basal estrogen production but attenuate FSH-stimulated estrogen production in vitro in rat granulosa cells. Here we present evidence that TGF alpha stimulates basal estrogen production in prepubertal porcine ovarian granulosa and theca cells in culture under defined conditions. In granulosa cells, TGF alpha is more potent than FSH in stimulating estrogen production. LH does not stimulate estrogen production in prepubertal porcine theca cells but rather attenuates that stimulated by TGF alpha. Treatment of follicular cells with genistein (inhibitor of protein tyrosine kinase) attenuates TGF alpha-induced estrogen biosynthesis suggesting that the action of TGF alpha is mediated through protein tyrosine kinase. These studies provide evidence for an alternative cAMP-independent and TGF alpha-induced tyrosine kinase-dependent mechanism for the induction of ovarian aromatase. PMID- 1935811 TI - Cortisol in vivo increases FSH beta mRNA selectively in pituitaries of male rats. AB - Cortisol treatment for 6 or 12 days had no effect on serum FSH in intact males and animals castrated for 1 or 7 days, but pituitary FSH was increased by the steroid in both intact and castrate groups. In contrast, cortisol inhibited serum LH in both intact and castrated animals while only increasing pituitary levels of LH in 7 day castrates. Cortisol also increased the mRNA for FSH beta without affecting alpha or LH beta mRNAs. These data suggest that the selective increase in pituitary content of FSH may be due to a selective increase in FSH beta mRNA following exposure to cortisol. PMID- 1935812 TI - Molecular order and fluidity of the plasma membrane of human platelets from time resolved fluorescence depolarization. AB - The ability of seven fluorescence polarization probes (1,6-diphenyl-1,3,5 hexatriene, 1-[(4-trimethyl- amino)phenyl]-6-phenyl-1,3,5-hexatriene, (2-carboxy- ethyl)-1,6-diphenyl-1,3,5-hexatriene, 16(9-anthroyloxy)-palmitic acid, CIS parinaric acid, trans-parinaric acid and perylene) to report changes induced by temperature and Ca2+ in the plasma membrane of human platelets has been examined. The steady-state fluorescence anisotropy of the probes was compared after being incorporated into whole resting platelets, fragments of platelet plasma membrane and multilayers of lipids extracted from these membranes. In addition, we have investigated the molecular order and dynamics of the three preparations by time resolved fluorescence depolarization of DPH and CE-DPH as a function of temperature and Ca2+ concentration. The high values of the order parameters found in intact platelets (SDPH, 36 degrees C = 0.70) were almost identical to those in membrane fragments and lipid vesicles, suggesting that lipid-lipid interactions and, therefore, the lipid composition are the main factors influencing the probe order parameter. Other lipid interactions such as those with membrane proteins and intracellular components have little effect on the SDPH in platelets. These measurements also showed that the stationary fluorescence anisotropy of DPH and CE-DPH in platelets is largely determined (80%) by the structural order of the lipid bilayer. Therefore, the previous "microviscosity" values based on stationary anisotropy data reflect the alignment and packing rather than the mobility of the bilayer components. The dynamic component of the anisotropy decay of these probes was analyzed in terms of the wobbling-in-cone model, allowing an estimation of the apparent viscosity of platelet plasma membrane (eta DPH, 36 degrees C = 0.5 P) that is similar to that of the erythrocyte membrane. This value decreased substantially in multilayers of native lipids, indicating a large effect of the lipid-protein interactions on the probe dynamics within the bilayer. When the temperature was raised from 25 degrees to 36 degrees C a pronounced decrease was observed in the order parameter and apparent viscosity, followed by a tendency to level-off in the 36 degrees-40 degrees C interval. This may be related to the end-point of the lipid phase separation reported by Gordon et al. (1983). Finally, the rigidifying (lipid ordering) effect of Ca2+ on the platelet plasma membrane could also be observed by the fluorescence anisotropy measurements, in the form of an increase (approximately 2%) of the order parameter of CE-DPH for Ca2+ concentrations in the millimolar range. PMID- 1935814 TI - Conformational transitions and hydration of poly d(A-T).poly d(A-T) in fibers. AB - Conformational transitions of poly d(A-T).poly d(A-T) have been studied by fiber X-ray diffraction and measurement of fiber dimensions. Results obtained for the D A-B and D-B transitions are presented and analyzed. For all these form transitions, cooperativity effects are observed for the variation of the rise per nucleotide versus the relative humidity. Detailed information about hydration of the polynucleotide during form transitions and the numbers of water molecules per nucleotide necessary to stabilize the different helical conformations are presented. PMID- 1935813 TI - Lateral heterogeneity in human platelet plasma membrane and lipids from the time resolved fluorescence of trans-parinaric acid. AB - We have investigated the complex behaviour of the time resolved fluorescence intensity and anisotropy of trans-parinaric acid, incorporated into fragments of the plasma membrane of human platelets and in multibilayers of lipids extracted from that membrane. It is shown that the observation of anisotropies that increase at long times can be satisfactorily interpreted by assuming two populations of the fluorescence probe with distinct life-times, rotational relaxation times and order parameters. The heterogeneous probe distribution was correlated with a similar heterogeneity in the lipid composition of the bilayer, modulated by temperature. Below 35 degrees C an important fraction of the lipids of the plasma membrane are apparently in the form of solid-like domains (20% at 20 degrees C). However, in the physiological temperature range that solid/fluid heterogeneity is almost negligible. Since these effects were also observed in multibilayers of lipids from the platelet membrane, the formation of solid-like clusters appears to arise from lipid-lipid interactions only, and most probably involving cholesterol. These results support the previous finding of a lateral phase separation for temperatures less than 37 degrees C described by Gordon et al. (1983) in a spin-probe study of the platelet plasma membrane. PMID- 1935815 TI - Lipid-protein surface films generated from membrane vesicles: selfassembly, composition, and film structure. AB - Lipid-protein films at the air-water interface were generated from a variety of native vesicles and from vesicles derived from lipid extracts. A technique is described which is particularly suitable for the generation of films from small amounts of material at high yield and velocity. In all instances, 10 microliters vesicle suspensions containing 25 micrograms protein yield at least 50 cm2 film area at a constant surface pressure of 12 mN/m within minutes. Upon formation, surface films are separated from vesicles by use of shear forces. Complete separation is demonstrated by electron microscopy and surface pressure-area diagrams. The latter confirms previous conclusions that surface films generated from lipid vesicles are organized as a monolayer. Analysis of lipid-protein surface layers reveals that their lipid to protein ratios match those of the vesicles used, within a factor of two, irrespective of whether films are generated at high or low surface pressure. Surface denaturation of membrane proteins is shown to be effectively prevented when the film is generated and held at high surface pressure (greater than or equal to 15 mN/m). Upon surface pressure jumps from high to low values, denaturation kinetics revealed activation areas of 1.5 (+/- 0.2) nm2. PMID- 1935816 TI - Phloretin affects the fast potassium channels in frog nerve fibres. AB - The effect of phloretin (20-100 microM), a dipolar organic compound, on the voltage clamp currents of the frog node of Ranvier has been investigated. The Na currents are simply reduced in size but not otherwise affected. Phloretin has no effect on the slow 4-aminopyridine-resistant K channels. However, the voltage dependence and time course of the fast K conductance (gK) is markedly altered. The gK (E) curve, determined by measuring fast tail currents at different pulse potentials, normally exhibits a bend at -50 mV, indicating the existence of two types of fast K channels. Phloretin shifts the gK (E) curve to more positive potentials, reduces its slope and its maximum and abolishes the distinction between the two types of fast K channels. The effect becomes more pronounced with time. Phloretin also markedly slows the opening of the fast K channels, but has much less effect on the closing. Opening can be accelerated again by a long depolarizing prepulse which presumably removes part of the phloretin block. It is concluded that phloretin selectively affects the fast K channels of the nodal membrane. The results are compared with similar observations on the squid giant axon. PMID- 1935817 TI - Optical diffraction by well-ordered muscle fibres. AB - We have studied the diffraction of a focussed laser beam by single fibres of glycerinated rabbit psoas muscle as a function of the angle of incidence. Diffraction efficiencies as high as 34% were observed at the first-order Bragg angle, indicative of well-ordered striated fibres with a strong periodic modulation of the refractive index. A theory is presented to account for our observations based upon the coupled-wave model developed by Kogelnik (1967) and Magnusson and Gaylord (1977) for the description of thick phase gratings in holography. We have solved the coupled-wave equations on a computer using a realistic index modulation taken from the measurements of Huxley and Hanson (1957). Comparison of theory with experiment shows that coupled-wave effects are indeed present in well-ordered muscle fibres, and the observed diffraction efficiency is in quite good agreement with what would be expected theoretically. Most importantly, the computer model allows us to calculate the diffraction efficiency for curved striations, which are observed for real muscle fibres under a microscope. The sensitivity of the diffraction efficiency to curvature of the striations may have implications for the interpretation of other optical experiments on muscle. We also consider the effects on our measurements of the focussing lens and refraction by the cylindrical fibre. PMID- 1935818 TI - Human growth hormone replacement therapy: pharmacological and clinical aspects. PMID- 1935819 TI - LIF: not just a leukemia inhibitory factor. AB - Increasingly it seems that many cytokines are pleiotropic, and individual molecules may have critical roles in several different organ systems. LIF exemplifies this phenomenon: it influences embryogenesis, bone and lipid metabolism, and hematopoietic and nervous system function. Many of LIF's effects are reminiscent of those of IL-1, TNF, and TGF-beta. Further, even within a single system, LIF can display totally different effects, i.e. induction of differentiation of one leukemic cell line vs. stimulation of proliferation of another. The corollary to these observations is that there appears to be many parallels in developmental systems. For instance, in the case of neuronal "lineage commitment," the events that relate to migration of neural crest cells along various pathways and their ultimate arrest in different locales demonstrate sufficient analogies to hematopoietic lineage commitment phenomena that, in a provocative review, Anderson coined the term "neuropoiesis". This type of analogy becomes even more intriguing when one realizes that some of the same molecules are regulating neuronal and hematopoietic "lineage" proliferation and differentiation. In this respect, several interleukins in addition to LIF are important in neuronal development, and nerve growth factor turns out to also be a hematopoietic regulatory molecule. Similar parallels are enacted in other organ systems as well. The mediation of identical effects by distinct cytokines bound to unique receptors could conceivably be explained by receptor transmodulation or by overlapping signaling sequences. It is nevertheless also unclear how a single cytokine attached to a single receptor can accomplish varied and opposing effects, although divergent intracellular signaling mechanisms could account for some of these phenomena. Yet another enigma relates to how cells from one system can be properly influenced by a pleiotropic molecule such as LIF without significant "cross-effects" on other potentially responsive systems. Cytokine production that is restricted to certain developmental stages, or very localized distribution and spheres of influence within a microenvironment, could be explanatory. The findings of Rathjan and colleagues, i.e. that LIF exists as both a diffusible molecule and as a molecule incorporated into the extracellular matrix, is of special interest in relation to the above questions. Indeed, the distinctions between the roles of diffusible and immobilized signaling molecules could be crucial to the multiplicity of LIF's actions. Diffusible regulatory factors allow communication between spatially separated cells. Cellular responsiveness to such factors is dictated by the presence of appropriate receptors and postreceptor machinery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935820 TI - The prolactin/growth hormone receptor family. AB - PRL and GH are hormones with a wide spectrum of actions. Specific receptors are widely distributed in a number of classical target organs, but other tissues that are not known targets also contain measurable binding sites or receptor mRNA. The most likely explanation is that PRL and GH cause effects that have not yet been characterized in certain tissues. Cloning of the cDNAs encoding PRL and GH receptors has led to the discovery that the receptors, like the hormones themselves, form a gene family. Multiple receptor forms have been identified, including a short form, which for PRL is a membrane-bound receptor or for GH is a soluble BP, and a long form, which for both PRL and GH is a membrane-bound receptor. PRL and GH receptors, and the mRNAs encoding them, can be up- and down regulated. GH induces an up-regulation of both GH and PRL receptors, whereas PRL stimulates an increase of only its own receptor. High concentrations of either hormone induce a homologous down-regulation of receptor expression. An assay has been developed to measure the functional activity of different forms of PRL receptor by cotransfecting a milk protein fusion gene specific to PRL coupled to a reporter-gene along with the cDNA of the PRL receptor. Although the short form represents the major form present in rat mammary gland, only the long form of receptor is able to stimulate milk protein gene transcription. For GH, increased expression of the receptor in some target cells is accompanied by a modest enhancement of the response to GH. No single second messenger mediating the action of either PRL or GH has been identified. Several potential components of the signal transduction pathways have been identified, but as yet none has clearly been shown to be able to mimic the effect of PRL or GH. Because of the wide range of biological actions associated with PRL, and the existence of various forms of PRL receptors, it is doubtful that one unifying mechanism of action will be found for this hormone. No human or animal model of a genetic defect of the PRL receptor has thus far been published. Mutations in the GH receptor gene have been demonstrated in Laron type dwarfism. Different exon deletions or point or nonsense mutations resulting in modifications in the extracellular, GH binding region of the GH receptor have been reported.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935821 TI - Structure and pancreatic expression of the insulin and glucagon genes. PMID- 1935822 TI - Human endometrium: an active site of cytokine production and action. PMID- 1935823 TI - Regulation of parathyroid hormone secretion. AB - Calcium is the most important physiological regulator of PTH secretion. Peak PTH secretion occurs at an intracellular calcium concentration of about 200 nM, regardless of the extracellular calcium concentration. We suggest, therefore, that intracellular calcium concentration is a regulator of PTH secretion that maintains calcium homeostasis. Other factors may be responsible for modulation of the intracellular calcium concentration, ultimately modulating PTH secretion. The "paradoxical" nature of the dependence of PTH secretion on the calcium concentration may be explained by considering PTH secretion to be unusual in a quantitative, rather than a qualitative, fashion. A possible mechanism for the control of PTH secretion by intracellular calcium, which involves calcium activated potassium channels, is proposed. The parathyroid cell plasma membrane contains several sensors or channels by means of which the cell senses extracellular calcium. It is not clear whether these entities are coupled to each other or whether they function independently. Guanine nucleotide regulatory proteins are transducers of extracellular signals, including calcium. Several other second messengers that influence PTH secretion have also been described, but possible interactions between these messengers have not yet been determined. PMID- 1935825 TI - Citation for the Richard E. Weitzman Memorial Award of The Endocrine Society to Synthia H. Mellon. PMID- 1935824 TI - Citation for the Rorer Pharmaceutical Clinical Investigator Award of The Endocrine Society to Lawrence A. Frohman. PMID- 1935826 TI - Citation for the Edwin B. Astwood Lectureship of The Endocrine Society to Marc E. Lippman. PMID- 1935827 TI - Citation for the Robert H. Williams Distinguished Leadership Award to William D. Odell. PMID- 1935828 TI - Citation for the Ernst Oppenheimer Award of The Endocrine Society to Perrin C. White. PMID- 1935829 TI - Citation for the Fred Conrad Koch Award of The Endocrine Society to John T. Potts, Jr. PMID- 1935830 TI - Citation for the Distinguished Service Award of The Endocrine Society to Francine L. Trull. PMID- 1935831 TI - Structural and functional relationships between type II pneumocytes and components of extracellular matrices. AB - Type II pneumocytes of the pulmonary alveolus are dynamic cells with multiple functional capabilities in vivo, including secretion of surface-active lipoproteins and cell renewal of the epithelial lining of the alveolus, involving its differentiation into another cell type (the type I pneumocyte). The factors that influence and control these processes, which are vital to the function of the alveolus, have begun to be more clearly understood in recent years, in large part because of the development of adequate in vitro systems, which permit the manipulation of relevant variables. These appear to be a complex interaction between insoluble components of extracellular matrices, principally of the basement membrane, and soluble factors that include hormones and growth factors. This review focuses particularly on those components of extracellular matrices that specifically and nonspecifically impact on type II cell function, and it attempts to bring together the diverse technical approaches used to define and examine these relationships cytochemically and functionally. PMID- 1935833 TI - Biochemical and pharmacological characterization of ICI 186,756: a novel, potent, and selective inhibitor of human neutrophil elastase. AB - ICI 186,756 is a representative of a new chemical class of synthetic inhibitors of human neutrophil elastase (HNE). This compound demonstrated competitive inhibition of HNE with a Ki of 3.6 +/- 0.8 x 10(-9) mol/L. The selectivity of ICI 186,756 for HNE versus a variety of enzymes ranged from a minimum of 870-fold to greater than 640,000. The compound effectively inhibited hydrolysis of bovine ligamentum nuchae elastin by HNE. Pretreatment of hamsters with ICI 186,756 up to 2 h before intratracheal administration of HNE inhibited enzyme-induced increases in lung weight, total lavageable red cells, and total lavageable white cells measured 24 h after HNE administration. In contrast, similar lung effects produced by intratracheal administration of porcine pancreatic elastase (PPE) were not inhibited by ICI 186,756. Treatment of hamsters with 43 mumol/kg (sc) of ICI 186,756 for 14 or 28 days modulated the increases in alveolar diameter produced by both PPE and HNE, respectively. It is concluded that ICI 186,756 is a potent, competitive, and selective inhibitor of HNE that may be useful in understanding the role of this enzyme in animal models of various diseases. Furthermore, the maintenance or progression of emphysema-like lesions induced in hamsters by PPE do not appear to be due to the persistence of that enzyme within the lung. PMID- 1935832 TI - Vitamin E distribution and modulation of the physical state and function of pulmonary endothelial cell membranes. AB - Vitamin E, a dietary antioxidant, is thought to incorporate into the lipid bilayer of biological membranes. We evaluated the lipid composition and distribution of [3H]-vitamin E in various membranes of pulmonary endothelial cells and determined whether vitamin E incorporation caused alterations in membrane structure and function in these cells. Following 6-, 12-, 18-, 24-, and 48-h incubation periods, vitamin E incorporation values were 3.0, 5.7, 6.9, 7.2, and 6.8 nmol/mg protein or 3.8, 7.3, 8.8, 9.2, and 8.7 nmol/mg phospholipid in mitochondrial membranes and 2.0, 4.4, 5.2, 5.3, and 5.0 nmol/mg protein or 3.5, 7.7, 9.1, 9.3, and 8.8 nmol/mg phospholipid in microsomal membranes, respectively. Vitamin E incorporation into the plasma membranes was greater than in mitochondrial and microsomal membranes after 12-, 24-, and 48-h incubations (18.9, 20.8, and 19.6 nmol/mg protein, respectively [P less than .001] versus mitochondria and microsomes or 12.2, 13.4, and 12.6 nmol/mg phospholipid, respectively [P less than .05] versus mitochondria and microsomes). The total phospholipid content, as well as the unsaturation index of the fatty acid content of these membranes, were in the same order, (i.e., plasma membrane greater than mitochondrial membranes and microsomal membranes). The physical state of the intact plasma membrane and the mitochondrial and microsomal membranes were measured by monitoring fluorescence anisotropies (rs) of the molecular probes, diphenylhexatriene (DPH) and trimethylamino-DPH (TMA-DPH). Vitamin E incorporation caused significant increases in rs for DPH (P less than .01) and TMA-DPH (P less than .01) in all three membranes compared to controls. Similar increases in rs values for DPH and TMA-DPH were observed in lipid vesicles prepared from these membranes. Following vitamin E incorporation, 5 hydroxytryptamine (5-HT) transport was measured as an index of plasma membrane function. Vitamin E incorporation resulted in an 18% reduction (P less than .05) in 5-HT uptake. These results indicate that vitamin E was distributed nonuniformly in endothelial cell membranes but resulted in comparable decreases in fluidity in all three membranes. In addition to its role as an antioxidant, vitamin E may alter the membrane physical state and modulate a variety of endothelial cell functions, including 5-HT transport. PMID- 1935835 TI - Effect of heart rate on aerosol recovery and dispersion in human conducting airways after periods of breathholding. AB - With a newly developed aerosol inhalation device, small volumes of aerosols ("boluses") can be inspired predominantly into the conducting airways of the human lungs. The aerosol is injected by a fast-operating valve system using preselected volumes near the end of a clean air inhalation of 1000 cm3. Particle behavior in upper human airways was investigated by measuring particle recovery and bolus dispersion in exhaled air with a laser photometer positioned directly in front of the mouth after various periods of breathholding. The effect of physical motion of the heart on these measurements has been investigated by increasing the heart rate of a subject by more than a factor of 2. Monodisperse sebacate aerosols were used with droplets in the aerodynamic size (dac) range between 0.8 and 1.1 micron to minimize particle losses by diffusion and by inertial forces. It was shown that motion of the heart considerably influences both particle recovery and dispersion of such boluses during postinhalation periods of breathholding. For a twofold enhancement in heart frequency the standard deviation of the expired aerosol bolus was increased by up to 60% after certain breathholding periods. Particle recovery from shallow volumetric lung depths was significantly decreased. PMID- 1935834 TI - In vivo effects of endotoxin on nasal epithelial mucosubstances: quantitative histochemistry. AB - Airway inflammation induced by gram-negative bacteria is often characterized by an influx of neutrophils and hypersecretion of mucus. The purpose of this study was to determine how endotoxin, a component of gram-negative bacteria and a chemotaxinogen for neutrophils, affects the amount of stored intraepithelial mucosubstances in the rat nasal airway. Rats were intranasally instilled, once a day for 3 days, with endotoxin or saline (controls). Before the first and third instillation, half of the animals were depleted of circulating blood neutrophils by administering a rabbit anti-rat neutrophil antiserum. Rats were sacrificed 6 or 24 h after the last instillation. Nasal tissues were processed for light microscopy and histochemical detection of stored intraepithelial mucosubstances. The numbers of nasal epithelial cells and intraepithelial neutrophils per millimeter of basal lamina in the anterior nasal septum and the amounts of intraepithelial mucosubstances in the same nasal tissue were determined by image analysis. We did not observe a neutrophil influx in the nasal tissues of neutrophil-depleted rats at 6 or 24 h after the last endotoxin instillation; however, we did observe a significant increase in intraepithelial mucosubstances, compared to saline-instilled controls. In contrast, nonneutrophil-depleted animals had a marked neutrophilic influx and a concomitant decrease in stored mucosubstances, compared to saline-instilled controls. There was no significant difference in the number of nasal epithelial cells per millimeter of basal lamina among any of the experimental groups. These results indicate (1) that endotoxin induces an increase in the amount of intraepithelial mucosubstances only when intraepithelial neutrophils are absent, and (2) that the endotoxin-induced, neutrophil influx probably triggers mucous hypersecretion. PMID- 1935836 TI - Effect of platelet-activating factor on glycogen metabolism in fetal rat lung. AB - Platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, or PAF) has previously been shown to induce glycogenolysis in the perfused adult rat liver and in the lung and liver of 24 day (gestational age) fetal rabbits in utero. In the present report, the effect of PAF was examined in fetal rats that were intravenously injected (through the vitellin vein) at a stage in their gestational development characterized by rapid glycogen depletion and surfactant accumulation. At 24 h after PAF administration of 2.5 micrograms and 5.0 micrograms to 19.5- and 20.5-day-old fetal rats, respectively, the lung glycogen content decreased significantly. In contrast, the inactive enantiomer of PAF did not modify the glycogenolytic response in vivo. When [14C]glucose (5 muCi) and PAF (5 micrograms) were simultaneously injected through the vitellin vein of the fetus, the radioactivity incorporated into lung glycogen was reduced as compared with control fetuses receiving the vehicle alone. An additional effect of PAF was noted in experiments designed to correlate glycogen breakdown to surfactant phospholipid biosynthesis. An inhibition of [3H]choline uptake and incorporation into phospholipids of fetal human lung explants and fetal lung type II pneumonocytes was induced by PAF. It is concluded that PAF appears to be a potential inducer of glycogen breakdown in the fetal lung and the relationship of these findings to fetal lung maturation is discussed. PMID- 1935837 TI - Rabbit alveolar macrophages stimulated with endotoxin and lung fragments from endotoxemic rabbits produce a leukocyte infiltration-inducing factor that lacks IL-1, TNF alpha, or chemotactic activity. AB - We reported previously that rabbit pleural and peritoneal macrophages (Mos) and human Mo stimulated with endotoxin (LPS) release a protein factor of 45 to 60 kd that induces local polymorphonuclear leukocyte (PMNL) infiltration upon intradermal injection in rabbits. In the case of the human Mo product, it was shown to be distinct from interleukin-1 (IL-1), tumor necrosis factors (TNF alpha), granulocyte macrophage colony stimulating factor (GMCSF), IL-6, and lower molecular weight PMNL chemotactic factors. Here, we examined resident rabbit alveolar Mos to determine if they produce a similar factor following in vitro or in vivo exposure to LPS. Following LPS exposure (0.3 to 30 ng/ml), alveolar Mos obtained from normal rabbits by bronchoalveolar lavage released PMNL recruiting activity within 3 h, as measured by the accumulation of 51Cr labeled blood PMNL at injected skin sites. Production of this activity was blocked by cycloheximide; it was heat labile and not affected by polymyxin B, which neutralized the LPS. On gel filtration chromatography, a major peak of activity was eluted at 45 to 60 kd and was free of IL-1 but partially overlapped with rabbit TNF alpha. Although active in vivo in PMNL recruitment into the tissues, these fractions did not induce PMNL migration in vitro in a filter chemotaxis assay. After sodium dodecyl sulfate (SDS), polyacrylamide gel electrophoresis (PAGE) the predominant PMNL recruiting factor (PRF) eluted from gel slices corresponded to 22 to 32 kd, suggesting that this protein is a dimer under gel filtration conditions. These gel eluates did not contain TNF alpha activity. Following iv administration of sublethal doses of LPS (3 micrograms/kg) or of antibiotic killed Escherichi coli (10(9)/kg), peripheral lung fragments from perfused lungs spontaneously produced this PRF during ex vivo culture without further LPS stimulation. Lung tissue from normal rabbits did not release PRF spontaneously. We conclude that resident alveolar Mos produce a PRF protein in response to LPS that is distinct from IL-1, TNF alpha, and chemotactic factors and that the production of a similar protein by lung cells (probably Mos) is probably induced in vivo during endotoxemia or bacteremia. This factor may contribute to PMNL accumulation in the lung during pathologic processes. PMID- 1935838 TI - Reciprocal epithelial: fibroblast interactions in the control of fetal and adult rat lung cells in culture. AB - Intercellular communication between epithelial cells and fibroblasts of the alveolar wall has been postulated from studies of lung development and repair. We examined the epithelial cell-fibroblast interactions with respect to growth control and epithelial cell function using cultured fetal and adult lung cells. The role of diffusing factor(s) as compared to direct cell-to-cell contact was studied by culturing epithelial cells either on a permeable culture well insert over fibroblasts or in co-culture with fibroblasts. The results show that the normal low proliferative rate of epithelial cells in culture is increased when exposed to fibroblast supernatants. In contrast, epithelial cells (particularly from adult lung) secrete a factor that suppresses fibroblast growth when cultured with a filter between the cell types. However, when cell-cell contact occurs in co-culture, the growth rate of fibroblasts is greatly increased. Synthesis of disaturated phosphatidylcholine by epithelial cells is increased under serum-free conditions and further rises when fetal epithelial cells are exposed to steroid treated fibroblasts, when the cell types are separated, and when cells are in contact. This indicates that a fibroblast-derived factor stimulates epithelial differentiation, and morphologic evidence relating the appearance of lamellar bodies to the areas of direct epithelial cell-fibroblast contact was found. The results indicate the complex interdependence of these two types of cell where a secretory product of one cell or direct cell-cell contact may alter when regulatory control of the other cell type. These interactions are likely to be important in orderly development and in the reparative response of the lung to injury. PMID- 1935839 TI - Oral bioavailability of chromium from a specific site. AB - Analysis of soil from a specific site in New Jersey indicated a low level of sodium and chromium present as a calcium compound. Chromium was then administered orally to young, mature male rats at a level of 240 micrograms/kg for 14 days as chromium-contaminated soil, as CaCrO4, and as an equimolar mixture of the soil and calcium salts for 14 days. The rats were sacrificed 24 hr after the last dosing, and tissues were taken immediately for chromium analysis. Blood, muscle, and liver contained the highest levels of chromium in these animals, although kidney contained the highest concentration per gram of tissue. The total amount of chromium in the tissues was less than 2% of the administered chromium. In a study of the excretion of chromium, the animals were dosed orally for 8 days (with CaCrO4 or contaminated soil, each at the level of 240 mumole Cr/kg), and the chromium in feces and urine was determined on days 1, 2, 7, and 8. After cessation of dosing for 27 days, the same rats were dosed for 2 days at the same level, and chromium in urine and feces was determined for the 2 days. The animals administered the chromium in soil had higher levels of chromium in both urine and feces on all days compared to the group fed the CaCrO4. The total recovery of chromium in any of the 2-day periods was less than 50% of the chromium administered during that period. PMID- 1935840 TI - Skin permeation and cutaneous hypersensitivity as a basis for making risk assessments of chromium as a soil contaminant. AB - A literature review of experimental and human exposure studies of skin permeation and cutaneous hypersensitivity reactions evoked by chromium was carried out to provide a basis for making a risk assessment of chromium as a soil contaminant. In vitro and in vivo studies demonstrated that 1 to 4% of the applied dose of hexavalent and trivalent chromium to guinea pig skin penetrated skin within 5 to 24 hr after application. Ultrastructural investigations showed that hexavalent chromium localized intracellularly and extracellularly in the upper layers of guinea pig epidermis. Only minute quantities of hexavalent chromium are required to elicit a positive hypersensitivity reaction in susceptible individuals; using a patch dose of 20 micrograms, only 2 micrograms were required to evoke a positive skin reaction in hypersensitive subjects. The potential of hexavalent chromium to produce a skin sensitization reaction is readily demonstrated using animal models. The incidence and characteristics of chromium-induced skin hypersensitivity as a clinical entity are described. A health effects survey of populations exposed to chromium slag in soil in Tokyo, Japan extending over 8 years indicated a tendency toward symptoms characterized as headache, chronic fatigue, and gastrointestinal complaints, positive occult blood tests, minute hematuria and albuminuria suggestive of incipient renal disease, and a tendency toward an increase in contact dermatitis that was seasonally related. Multicenter patch test titration studies in human subjects using an incidence of positive patch tests of 10% or less showed that the threshold for skin hypersensitivity reactions to hexavalent chromium was determined to be of the order 0.001%, equivalent to 10 ppm or 10 mg/kg or 10 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1935841 TI - Mechanisms of toxicity/carcinogenicity and Superfund decisions. AB - Heavy metals that contaminate soils and water usually exist in various oxidation states and form a number of compounds with different physical and chemical characteristics. These differences are often reflected in dramatic variation in toxicokinetic and biologic properties. Such variation in properties, critical in determining intrinsic toxicity, often causes a great deal of uncertainty in analyses of public health risks at sites where metal exposure is evaluated. In the Superfund program, such uncertainties may substantially undermine attempts to characterize potential impacts to populations exposed to metals from improperly disposed waste. In the case of chromium, risk assessment uncertainties can be considerable and fall generally into two categories. First, there is almost no information on potential health effects due to chronic oral exposure to chromium containing compounds, and a nonquantifiable and probably large uncertainty exists in establishing no-effect levels. In fact, reference doses (RfDs) for CrIII and CrVI are based on chronic studies in which no adverse effects were seen even at the highest dose. Considerations of bioavailability, deduced from site characterization data, and acute toxicity indicate that general application of these RfDs may lead to highly inaccurate estimations of risk. Second, because of the ready reduction of CrVI in biological systems, it has not been possible to separate effects of CrVI from those of CrIII. Thus, data on the relative toxicity and carcinogenicity of these two species is sparse and difficult to interpret. Moreover, kinetic considerations make it difficult to determine the site and rates of reduction of CrVI. This makes prediction of target site concentrations of the two species difficult.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1935843 TI - Chromite ore processing residue in Hudson County, New Jersey. AB - Chromite ore processing residue occurs at over 130 sites in Hudson County, New Jersey. Many of these sites are in urban residential areas. This waste is a result of 70 years of chromate and bichromate chemical manufacturing. At least 15% of the sites contain total chromium concentrations greater than 10,000 mg/kg, with hexavalent content ranging from about 1 to 50%. Continuing leaching of this waste results in yellow-colored surface water runoff and yellow deposits on the soil surface and inside basement walls. The chemistry, environmental fate, health effects, and human exposure potentials for this waste are described. PMID- 1935842 TI - The analytical biochemistry of chromium. AB - The essentiality and carcinogenicity of chromium depend on its chemical form. Oxidation state and solubility are particularly important in determining the biological effects of chromium compounds. For this reason, total chromium measurements are of little value in assessing its nutritional benefits or its toxicological hazards. Aqueous sodium carbonate-sodium hydroxide solutions have been successfully used for extracting hexavalent chromium from a variety of environmental and biological matrices while preserving its oxidation state. Typical recoveries are 90 to 105% in samples spiked with both trivalent and hexavalent chromium. Determination of hexavalent chromium after extraction with sodium carbonate-sodium hydroxide solution, coupled with the determination of total chromium after nitric acid-hydrogen peroxide digestion, has been applied to the evaluation of chromium speciation in airborne particulates, sludges, and biological tissues. PMID- 1935844 TI - Composition and health hazards of water-based construction paints: results from a survey in the Netherlands. AB - Water-based construction paints may have beneficial effects toward man's occupational and general environment when compared to traditional paints that contain large amounts of organic solvents. The aim of this study was to describe the health hazards of the application of these alternative paints. The composition of these paints was obtained by a questionnaire survey among the main producers and importers in The Netherlands. Physicochemical parameters and toxicity data of the constituents were used to estimate occupational and environmental health hazards. Mucous membrane of skin irritation and sensitization are predicted to be the most frequently occurring health hazards after contact with these paints during professional or do-it-yourself application. Health hazards from environmental pollution may be irritation of the mucous membranes when the indoor environment is painted and fish mortality due to slowly degradable polyacrylate binders. The health hazards can be reduced by replacing some toxic compounds with less toxic ones and by hygienic (ventilation, skincare, no cleaning of application materials under the tap) measures. PMID- 1935845 TI - Two-stage and Weibull models for carcinogenesis applied to the ED01 discontinued dosing data. AB - The two-stage clonal expansion model for a single, less-than-lifetime period of dosing is formulated and applied to the liver and bladder tumor data from the ED01 study. The model successfully predicts liver tumor incidence for time points beyond termination of dosing with 2-acetylaminofluorene, but it is unsuccessful for bladder tumor incidence. A discontinued dosing version of the Weibull model is proposed and is shown to predict successfully both liver and bladder tumor incidences for time points after termination of dosing. PMID- 1935847 TI - Chromium cycling in soils and water: links, gaps, and methods. AB - The major links in the cycling of chromium in soils and in natural waters are between chromium(III) and chromium (VI). Between the larger links are lesser links involving processes of mobilization and oxidation of CrIII and reduction of CrVI. The gaps are mainly in our understanding of the factors that control these processes. If soluble CrIII is added to an "average" soil, a portion of it will become immediately oxidized by manganese oxides to CrVI. The rest of the CrIII may remain reduced for long periods of time, even in the presence of electron accepting manganese oxides. However, this less available CrIII can be mobilized by low molecular weight organic complexers and then oxidized where redox conditions are optimal. Usually part of any CrVI added to a soil or sediment will be reduced instantly, especially under acid conditions. On the other hand, high concentrations of polluting CrVI may quickly exhaust the readily available reducing power of the matrix material and excess CrVI, the thermodynamically stable form in air, may persist for years in soils or lagoons without reduction. Cleanup of chromium pollution must involve the surrounding of both CrIII and CrVI with excesses of slowly available reducing substances and sealing them permanently from inputs of atmospheric oxygen. Monitoring the effectiveness of the measures is mandatory, but fortunately the chemical testing for CrVI in soil and water is simple and problem free compared with most colorimetric determinations. PMID- 1935846 TI - p-Nonyl-phenol: an estrogenic xenobiotic released from "modified" polystyrene. AB - Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large. PMID- 1935848 TI - Public inquiries about indoor air quality in California. AB - To identify the indoor air quality issues about which Californians most often sought advice from a health department or a public information agency and to evaluate how well these agencies met the public's needs, members of the California Interagency Working Group (IWG) on Indoor Air Quality kept records of inquiries they received over a 30-month period from mid-1985 through 1987. Members of the IWG answered calls from residents of a least 49 of California's 58 counties. IWG members received more public inquiries about residences than about offices, educational institutions, commercial buildings, or medical facilities. However, each call about a residence probably represented fewer people at risk of exposure to a real or a potential problem than did calls about other types of buildings. Homeowners themselves asked the majority of the questions about residences, whereas a large number of the inquiries about office buildings were made, not by affected office workers, but by building managers, contractors, consultants, or company health and safety officers. The leading topics of concern in the residences were asbestos, chemical and biological contamination, and radon. In offices, chemical contamination, the ventilation system, biological contamination, asbestos, and tobacco smoke were the most frequently mentioned sources of problems. Callers often reported experiencing headaches, allergy symptoms, nose or throat irritation, and respiratory tract problems in connection with their complaints. IWG members directed a third of the calls elsewhere, of which half were referred to consultants or testing laboratories. The IWG's experience in the State of California could help other health departments prepare to face the public's increasing concern about indoor air pollution. PMID- 1935849 TI - Processes affecting the remediation of chromium-contaminated sites. AB - The remediation of chromium-contaminated sites requires knowledge of the processes that control the migration and transformation of chromium. Advection, dispersion, and diffusion are physical processes affecting the rate at which contaminants can migrate in the subsurface. Heterogeneity is an important factor that affects the contribution of each of these mechanisms to the migration of chromium-laden waters. Redox reactions, chemical speciation, adsorption/desorption phenomena, and precipitation/dissolution reactions control the transformation and mobility of chromium. The reduction of CrVI to CrIII can occur in the presence of ferrous iron in solution or in mineral phases, reduced sulfur compounds, or soil organic matter. At neutral to alkaline pH, the CrIII precipitates as amorphous hydroxides or forms complexes with organic matter. CrIII is oxidized by manganese dioxide, a common mineral found in many soils. Solid-phase precipitates of hexavalent chromium such as barium chromate can serve either as sources or sinks for CrVI. Adsorption of CrVI in soils increases with decreasing chromium concentration, making it more difficult to remove the chromium as the concentration decreases during pump-and-treat remediation. Knowledge of these chemical and physical processes is important in developing and selecting effective, cost-efficient remediation designs for chromium-contaminated sites. PMID- 1935850 TI - Setting the research agenda for chromium risk assessment. PMID- 1935851 TI - DNA-protein complexes induced by chromate and other carcinogens. AB - DNA-protein complexes induced in intact Chinese hamster ovary cells by chromate have been isolated, analyzed, and compared with those induced by cis-platinum, ultraviolet light, and formaldehyde. Actin has been identified as one of the major proteins complexed to DNA by chromate based upon its molecular weight, isoelectric point, positive reaction with an actin polyclonal antibody, and proteolytic mapping. Chromate and cis-platinum both complex proteins of similar molecular weight and isoelectric points, and these complexes can be disrupted by chelating agents and sulfhydryl reducing agents, suggesting that the metal itself is participating in binding rather than having a catalytic or indirect role (i.e., oxygen radicals). In contrast, formaldehyde complexed histones to the DNA, and these complexes were not disrupted by chelating or reducing agents. An antiserum raised to chromate-induced DNA-protein complexes reacted primarily with 97,000 kDa protein that did not silver stain. Slot blots, as well as Western blots, were used to detect formation of p97 DNA crosslinks. This protein was complexed to the DNA by all four agents studied. PMID- 1935853 TI - The chemistry of chromium and some resulting analytical problems. AB - Chromium, named for its many-colored compounds, exists in the oxidation states of -2 to +6 inclusively. The compounds exhibit a wide range of geometries including square planar, tetrahedral, octahedral, and various distorted geometries. Chromium is found in nature principally as the chromite ore FeCr2O4 in which chromium is in the +3 state. The existence of a particular oxidation state is dependent on many factors including pH, redox potentials, and kinetics. Thermodynamically, +3 and +2 are the most stable states, while the +3 and +6 oxidation states are the most common ones found in aqueous solution. Kinetically, chromium +3 is substitutionally inert: for water exchange k(sec-1) = 2.5 x 10( 6), due to the presence of the half-filled d(t2g)3.4A2g state. On the other hand, protonation/deprotonation is quite rapid. Polymerization is very slow but is promoted at higher pHs; acid cleavage of the protonated oligomers is also quite slow. Chromium +6 as the chromate ion is strongly oxidizing at low pHs and less so in basic solution. The chromate ion does form some polyacids and polyanions. These factors must be considered in analyzing samples for total chromium and for the amounts of each oxidation state. PMID- 1935852 TI - Effects of vitamins on chromium(VI)-induced damage. AB - The effects of vitamin E and vitamin B2 on DNA damage and cellular reduction of chromium(VI) were investigated using Chinese hamster V-79 cells. Pretreatment with alpha-tocopherol succinate (vitamin E) resulted in a decrease of DNA single strand breaks produced by Na2CrO4, while similar treatment with riboflavin (vitamin B2) enhanced levels of DNA breaks. In contrast, levels of DNA-protein crosslinks induced by Na2CrO4 were unaffected by these vitamins. Electron spin resonance (ESR) studies showed that incubation of cells with Na2CrO4 resulted in the formation of both chromium(V) and chromium(III) complexes, and cellular pretreatment with vitamin E reduced the level of the chromium(V) complex, whereas pretreatment with vitamin B2 enhanced the level of this intermediate. However, the levels of chromium(III) were unchanged by these vitamins. The uptake of chromate was not affected by vitamin E or vitamin B2, nor were the levels of glutathione or glutathione reductase activity, which are both capable of reducing chromate. ESR studies demonstrated that a chromium(V) species was formed by the reaction of Na2CrO4 with vitamin B2 and that vitamin B2 enhanced the formation of hydroxyl radicals during the reaction of Na2CrO4 and hydrogen peroxide. Treatment cells with Na2CrO4 resulted in a decrease of glutathione reductase activity, and pretreatment with vitamin E restored the enzyme activity suppressed by this metal. However, pretreatment with vitamin B2 enhanced the inhibition of this enzyme by Na2CrO4. Using a colony-forming assay, pretreatment with vitamin E dramatically decreased the cytotoxicity of Na2CrO4, while pretreatment with vitamin B2 was found to result in only a decrease of cell lethality of this metal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1935854 TI - Chromium-induced kidney disease. AB - Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not yet been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent) (15 mg/kg body weight). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of beta 2 microglobulin, a specific proximal tubule brush border protein, and retinol binding protein has been reported among chrome platers and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chronic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced exposure may produce persistent renal injury. The absence of evidence of chromate-induced chronic renal disease cannot be interpreted as evidence of the absence of such injury. Rather, it must be recognized that no prospective cohort or case-control study of the delayed renal effects of low-level, long-term exposure to chromium has been published. PMID- 1935855 TI - A possible role for chromium(III) in genotoxicity. AB - Chromium is found in the environment in two major forms: reduced CrIII and CrVI, or chromate. Chromate, the most biologically active species, is readily taken up by living cells and reduced intracellularly, via reactive intermediates, to stable CrIII species. CrIII, the most abundant form of chromium in the environment, does not readily cross cell membranes and is relatively inactive in vivo. However, intracellular CrIII can react slowly with both nucleic acids and proteins and can be genotoxic. We have investigated the genotoxicity of CrIII in vitro using a DNA replication assay and in vivo by CaCl2-mediated transfection of chromium-treated DNA into Escherichia coli. When DNA replication was measured on a CrIII-treated template using purified DNA polymerases (either bacterial or mammalian), both the rate of DNA replication and the amount of incorporation per polymerase binding event (processivity) were greatly increased relative to controls. When transfected into E. coli, CrIII-treated M13mp2 bacteriophage DNA showed a dose-dependent increase in mutation frequency. These results suggest that CrIII alters the interaction between the DNA template and the polymerase such that the binding strength of the DNA polymerase is increased and the fidelity of DNA replication is decreased. These interactions may contribute to the mutagenicity of chromium ions in vivo and suggest that CrIII can contribute to chromium-mediated carcinogenesis. PMID- 1935856 TI - Issues in the risk assessment of chromium. AB - Although hexavalent chromium is well established as a human carcinogen by the inhalation route, there are significant uncertainties in the quantitative estimation of cancer risk. One of the important uncertainties is the assumption that the carcinogenic potency, determined under conditions of occupational exposure where most workers were cigarette smokers, applies to the nonsmoking individual in the general population. There is substantial evidence that carcinogenicity is a function of the rate of cell turnover in the target tissue. The chromate worker would be expected to have a relatively high rate of cell proliferation in the bronchial mucosa due to airborne irritants and smoking. The potency of chromium might therefore be relatively high under conditions of occupational exposure. This problem in quantitative risk assessment applies equally well to another important indoor pollutant, radon. PMID- 1935858 TI - Iron status in a group of long-stay mentally handicapped menstruating women: some dietary considerations. AB - As part of a longitudinal study aimed at assessing the dietary intakes and nutritional status of a group of long-stay mentally handicapped subjects, 15 women of menstruating age were considered for a substudy to assess the influence of intake levels of dietary iron, energy, tea, coffee and vitamin C on their iron status. The assessment comprised a week-long weighed dietary survey and the measurement of a number of haematological indices that included serum ferritin concentration. Information on duration of menses was also collected and included in the assessment. Two-fifths of the subjects assessed had a serum ferritin concentration less than 12 micrograms/l indicating iron deficiency, including one who was considered anaemic as suggested by a haemoglobin level less than 12 g/dl. Duration of menses showed a negative significant correlation with serum ferritin concentration. The mean iron intake in the group was 9.5 +/- 1.5 mg/day. Energy intakes were low and positively correlated with iron intake. Although serum ferritin showed no correlation with iron intake, it showed significant negative correlations with the daily and meal-time intakes of tea and a significant positive correlation with the meal-time intakes of vitamin C. The six iron depleted subjects were assessed as a separate group (Group I) in comparison with the other nine subjects who had a serum ferritin concentration greater than 12 micrograms/l. The results of this assessment showed that, while there were no significant differences in duration of menses or the mean daily intakes of iron and energy between the two groups. Group I subjects had significantly higher daily and meal-time intakes of tea and significantly lower meal-time intakes of vitamin C compared to Group II subjects. The study provides some evidence suggestive of an association between the iron deficiency states observed and tea intake in adversely affecting iron status, particularly in the absence of adequate meal-time intakes of vitamin C. The findings from the study also suggest that long-stay mentally handicapped women of menstruating age, in addition to their handicap and dependency states which may often predispose them to a low dietary intake, are at particular risk of iron deficiency. PMID- 1935857 TI - Chromium and disease: review of epidemiologic studies with particular reference to etiologic information provided by measures of exposure. AB - Dozens of epidemiologic studies have been conducted since the late 1940s in an attempt to elucidate the relationship between exposure to chromium compounds and increased rates of certain cancers observed in several industries. The relationship between employment in industries producing chromium compounds from chromite ore and lung cancer has been well established in numerous studies. The relationship between exposure to certain chromium-based pigments and chromic acid and lung cancer, although not as strong, is fairly well accepted. The data concerning emissions from stainless-steel manufacturing and disease are contradictory. Although individual studies have indicated excesses of gastrointestinal and occasionally other cancers in these industries, results are not consistent and not universally accepted. There is general agreement that chromite ore does not have an associated risk of cancer. Although the chromium compound (or compounds) responsible for disease have yet to be identified, there is general agreement that hexavalent species are responsible for these diseases and that the trivalent species are not. Hypotheses about the carcinogenicity of specific chromium compounds generally relate to their solubility in body fluids. These hypotheses, however, have generally been produced as a result of toxicologic, not epidemiologic, investigation. Well-designed epidemiologic studies incorporating detailed assessments of worker exposures have the potential to help elucidate causality, identify specific carcinogenic compounds, and quantify risk in humans, eliminating the need to extrapolate from animal data. Although the need for exposure data crucial to this effort was identified in the earliest epidemiologic studies of chromium, such studies have not been conducted. As a result, little more is known today about the relationship between this chemical and disease in humans than was known 40 years ago. PMID- 1935860 TI - Variation in measures of urea kinetics over four years in a single adult. AB - Urea kinetics was measured in a single woman on five occasions over four years by the prime/intermittent oral-dose method with [15N15N]-urea. On a nitrogen intake of 231 +/- 24 mg/kg/day, urea production was 198 +/- 22 mg/kg/day, with the urinary excretion of urea being 143 +/- 25 mg/kg/day. Urea hydrolysis and salvaging in the bowel was 55 +/- 6 mgN/kg/day. The coefficients of variation for production, 11 per cent, excretion, 18 per cent, and hydrolysis, 11 per cent, were similar to that for intake, 10 per cent, and substantially less than reported inter-individual variations from other studies. It is concluded that the method employed for measuring urea kinetics gives reproducible results and that the intra-individual variation in urea kinetics is much less than the inter individual variation. PMID- 1935859 TI - Contraceptive use and breast-feeding duration in rural Bangladesh. AB - The association between contraceptive use and breast-feeding duration was investigated in 2380 women in rural Bangladesh where women usually stop breast feeding once pregnant. Life table analysis showed that women receiving regular injections of depo medroxy progesterone acetate (DMPA) and those using non hormonal contraception breast-fed significantly longer than women using no contraception. In contrast, women using oral contraceptives (combination of 0.5 mg norgestrel and 0.05 mg ethinyl oestradiol) did not breast-feed longer than women using no contraception. It is suspected that prolongation of breast-feeding obtained by delaying the next pregnancy with this oral contraceptive was offset by the depressing effect of oestradiol on lactation. Thus, in communities where prolonged breast-feeding is associated with improved child survival, non-hormonal contraceptive methods, or injectable DMPA, should be preferred for lactating women to oestrogen-containing oral contraceptives. PMID- 1935861 TI - Within-subjects variation over 10 months in 24-hour energy expenditure at a fixed physical activity programme. AB - In order to estimate within-subjects variability in 24-hour energy expenditure at a fixed physical activity programme with a physical activity index of 1.30, this quantity was measured in four apparently healthy subjects once a month over 10 months. The coefficient of variation of the measurements was found to be between 2.7 and 4 per cent and in agreement with previously published data. PMID- 1935862 TI - Effects of three different calcium preparations on urinary calcium and hydroxyproline excretion in postmenopausal osteoporotic women. AB - Some authors have claimed that 'solubilized' calcium preparations are better absorbed than calcium carbonate, while others have reported that all forms are equally well absorbed. We measured radiocalcium absorption in 35 postmenopausal osteoporotic women and then gave them on three successive evenings, in random order, three different proprietary calcium preparations (Sandocal containing 1 g of effervescent calcium, Calsup containing 1 g of calcium as the carbonate, and Caltrate containing 1.2 g of calcium as the carbonate). The daily urinary calcium excretion rose significantly and similarly on all three supplements and was greater in the high calcium absorbers than the low calcium absorbers. The fasting urinary hydroxyproline excretion was significantly decreased the morning after administration of each preparation, and one-way analysis of variance showed no significant difference between the days of administration or the type of supplement. The decrease was greater for high absorbers than for low absorbers on all three supplements but the differences did not reach statistical significance. By 36 hours after the last calcium supplement the urinary hydroxyproline had returned to baseline. The response of hydroxyproline excretion (and by implication bone resorption) appears to be rapid in onset and short lived. Strict compliance is therefore important in patients on calcium therapy. PMID- 1935863 TI - Basal metabolic rates and metabolic economy in chronic undernutrition. AB - Basal metabolic rates (BMR) and body composition were measured in 130 adult Indian males, selected from three socio-economic groups. Results show a significantly lower BMR in the chronically undernourished, with a greater dependence on carbohydrate as fuel in the fasted state. When expressed as per kg body weight or kg fat-free mass (FFM), the BMRs are significantly higher in these individuals. The latter observations suggest variations in the contribution of viscera and skeletal muscle to the FFM, with a relatively greater visceral to muscle mass ratio. However, on adjustment for differences in weight and FFM by means of an analysis of covariance, the chronically undernourished (both urban and rural) have significantly lower BMRs. This indicates a 'metabolic economy' in these individuals, which could be attributable in part to their significantly lower serum T3 levels. When the subjects are classified on the basis of grades of chronic energy deficiency (CED), individuals with low body mass index (BMI) (less than 17 and below) are not similar in their basal metabolism. Those individuals from good socio-economic backgrounds with access to ad libitum energy and protein intake but with low BMI have comparable BMRs to the well nourished. It may therefore be unwise to classify all individuals with low BMI 'across the board' as suffering from CED. Socio-economic scaling may be a useful addition to the present classification of CED. PMID- 1935864 TI - Personal responsibility and control over our bodies: when expectation exceeds reality. AB - Good health has become more than a means to personal goals such as greater attractiveness and increased longevity. It symbolizes self-control, hard work, ambition, and success in life. Inherent in this symbolism is the concept that the individual controls behavior, which in turn controls health. Although control over one's life plays an important role in both physical and mental health, the concept of personal control also infers responsibility. Positive attributes are accorded to people who are healthy, but those who fall ill, or those with less than the perfect body, are blamed and are thought to be self-indulgent, lazy, or even irresponsible and immoral. There is a tendency to overstate the impact of personal behavior on health. However, biological realities shape the degree to which health is under the control of the individual. The positive effects of behavior change must be balanced with the limits imposed by biology. PMID- 1935865 TI - Behavioral economic analysis of activity choice in obese children. AB - Evaluated children's choice for sedentary versus vigorous activity. Experiment 1 assessed the influence of percent overweight (less than 20%, 20% to 80%, greater than 80%) on choice of a moderately liked vigorous activity at a constant variable ratio (VR) 2 reinforcement schedule versus a highly liked sedentary activity with the schedule varied from VR2 to VR32. All children chose the sedentary choice when the schedules were VR2. As the cost for sedentary activity increased, lean and moderately obese children switched to the vigorous activity, but the very obese children still chose the sedentary activity. Experiment 2 compared moderately obese children's choice between easily accessible, highly or least liked vigorous activities (VR2) and highly liked sedentary activity with the schedule varied from VR2 through VR16. When the reinforcement schedules were equal, and sedentary activity and vigorous activity were rated as equally linked, children chose the sedentary activity. All subjects switched from the sedentary to the vigorous activity, but there were no differences in choice as a function of liking for vigorous activities. PMID- 1935866 TI - An investigation of cognitive-behavior therapy combined with oral valium for children undergoing painful medical procedures. AB - In previous research, a cognitive-behavioral therapy (CBT) package was found to be effective in reducing children's distress associated with the painful medical procedures of bone marrow aspirations (BMAs) and lumbar punctures (LPs). Orally administered Valium demonstrated less effectiveness but was helpful in reducing behavioral distress before the medical procedure. In the present study, we investigated whether the combination of oral Valium and CBT would result in increased efficacy of the CBT. Eighty-three subjects were randomly assigned to receive either CBT or CBT plus Valium while undergoing either a BMA or an LP. Dependent variables included observed behavioral distress, self-reported fear and pain, and pulse rate. Results failed to support the value of such a combination but did provide additional evidence in regard to the effectiveness of the CBT. The need for more potent medical interventions for some children is discussed. PMID- 1935867 TI - Dimensions of the severity of a health threat: the persuasive effects of visibility, time of onset, and rate of onset on young women's intentions to prevent osteoporosis. AB - Examined the persuasive effects of information about different aspects of the severity of a health threat. The research participants were 170 young women who were at risk for osteoporosis because they neither consumed an adequate amount of calcium daily nor performed an adequate amount of weight-bearing exercise. A message describing osteoporosis as disfiguring and highly visible increased beliefs in its severity and strengthened intentions to adopt the communicator's recommended preventive responses. In addition, compared with control conditions, describing the threat as likely to occur in the near future, as opposed to the distant future, also strengthened intentions. Furthermore, motivation to prevent osteoporosis remained high regardless of whether subjects believed it might occur to them in the near or distant future if they believed it was highly visible or disfiguring. The rate of onset (sudden or gradual) had no effect on intentions. Several implications for preventive health psychology are discussed. First, health promotion campaigns should, whenever possible, emphasize the immediate onset of a health threat and any visible features. Second, in order to convince people a health threat can be severe, the sudden rate of onset should be emphasized whenever possible. PMID- 1935868 TI - Use of diet pills and amphetamines to lose weight among smoking and nonsmoking high school seniors. AB - Used data on 3,305 high school seniors collected as part of the 1984 Monitoring the Future project to examine the relationships among cigarette use, diet pill use, and use of amphetamines for weight loss. Results indicate that females were more likely than males to report use of all three substances. In addition, Whites were more likely than Blacks to use all three substances. Both female and male smokers were more likely than nonsmokers to use diet pills. Amphetamine use for weight loss was positively related to smoking among females, but not among males. The relationships between smoking and diet pill use, and smoking and amphetamine use to lose weight, were maintained when race, sex, and other drug use were controlled simultaneously. Two explanations for these relationships are considered. The first is that smoking is related to the use of most other licit and illicit drugs. The second explanation is that there is a greater preoccupation with weight among smokers, with weight concerns potentially motivating the initiation of smoking. PMID- 1935869 TI - Predicting attempts and sustained cessation of smoking after the introduction of workplace smoking bans. AB - Examined predictors of smoking cessation attempts and predictors of the outcome of those attempts after the introduction of a workplace smoking ban. Smokers were surveyed in the month before the ban came into force, and variables collected at that time were used to predict outcomes 6 months later. Data from 491 respondents who were smokers at the time of the initial survey were used, and a set of potential predictor variables was chosen on both theoretical and empirical grounds. Making a cessation attempt was predicted by the strength of desire to quit and, to less extent, by not having been subject to extensive restrictions on smoking before the mandated ban, having tried to quit before, perceiving oneself high in ability to quit, and being worried about smoke at work. For the outcome of cessation attempts among those who tried, success was best predicted by low levels of a composite habit strength variable and, to less extent, by desire to quit, no previous attempts to quit, the existence of social supports for quitting, and educational status. Although cognitive variables were important in predicting attempts, they played only a minor role in predicting maintenance. Behavioral and environmental variables contributed slightly to prediction of attempts and strongly to prediction of maintenance. PMID- 1935870 TI - A national survey of older smokers: treatment needs of a growing population. AB - Examined smoking and quitting patterns among 289 smokers ages 50 to 74 years who took part in a nationwide survey of American Association of Retired Persons members. Respondents were predominantly chronic, heavy smokers. They had smoked for an average of 45 years, more than one third smoked 25 or more cigarettes per day, and more than two thirds showed evidence of high nicotine addiction. Nonetheless, most were interested in quitting smoking and reported plans to quit in the next year. Concerns about missing or craving cigarettes; losing a pleasure; and being nervous, tense, or irritable after quitting were the most common barriers to quitting reported. These problems were rated as more serious by heavier, longer term smokers and by smokers with lower quitting self-efficacy. The variables most strongly associated with "contemplating" quitting were beliefs in quitting health benefits, recent attempts to quit or cut down, prior attempts to quit, and high self-efficacy. Limitations of these findings are discussed along with implications for the design of treatments geared to the special needs of older smokers. PMID- 1935871 TI - Desired control and felt control as mediators of stress in a dental setting. AB - Control-related variables have clearly affected stress responses in previous research (Thompson, 1981). Prior work, however, has primarily emphasized the amount of control that subjects perceive they have. In the three studies reported here, we examined the added predictive utility of assessing subjects' desire for control. Data from all three studies indicate that subjects who have a high desire for control coupled with a low feeling of control are characterized by particularly high degrees of dental distress. These results were found both in settings where patients anticipated immediate dental treatment and where treatment was not imminent. In addition, the results indicate that this "at risk" group reported greater distress before and immediately after actual dental treatment. Furthermore, they remembered their dental treatment as being more aversive 1 week after treatment. The practical implications and theoretical significance of these data are considered. PMID- 1935872 TI - The Contemplation Ladder: validation of a measure of readiness to consider smoking cessation. AB - Presents evidence for the validity of the Contemplation Ladder, a measure of readiness to consider smoking cessation. Analyses of data collected from more than 400 smokers at two worksites before and during a 10-month intervention indicate that Ladder scores were significantly associated with reported intention to quit, number of previous quit attempts, perceived co-worker encouragement to quit, and socioeconomic status. Ladder scores predicted subsequent participation in programs designed to educate workers about their smoking habit and its contingent risks. The Ladder did not predict biochemically validated abstinence of 24 hr or more. To assess its ability to distinguish between groups known a priori to differ in readiness, we administered the Ladder to 36 participants in a clinic-based smoking cessation program. As predicted, clinic patients scored significantly higher than the workers on the Ladder. The importance of distinguishing between smokers at the lowest stages of readiness to quit is discussed. PMID- 1935873 TI - Long-term smoking intervention at the worksite: effects of quit-smoking groups and an "enriched milieu" on smoking cessation in adult white-collar employees. AB - Maximizing the potential of worksites for smoking intervention remains elusive. We hypothesized that long-term effectiveness of group intervention would be enhanced when offered within an "enriched milieu" (full program) compared with relative isolation (group only). The data failed to support the hypothesis. Although sustained abstinence rates were higher at full-program sites (50%) than at group-only sites (44%), the difference did not achieve statistical significance. Initial (35% vs. 47%) and 12-month (18% vs. 22%) quit rates at full program and group-only sites also failed to demonstrate the "benefit" of the "enriched milieu." PMID- 1935874 TI - Gel electrophoresis of polystyrene particles in glutaraldehyde crosslinked polyvinyl alcohol. AB - Polystyrene sulfate and carboxylate particles (19-189 nm radius) were subjected to electrophoresis in glutaraldehyde crosslinked polyvinyl alcohol of molecular weight 25.000 and 650.000 Da at various concentrations. The degree of crosslinking is severely limited by the mechanical properties of the gels that deteriorate beyond a glutaraldehyde concentration which decreases with increasing polyvinyl alcohol chain length. The effective fiber radius of the short-chain and long-chain polymer fiber was 45 +/- 25 and 131 +/- 47 nm, respectively. Thus, these media do not significantly exceed the apparent fiber thickness of agarose, are more difficult to prepare--but are well-defined synthetic products rather than natural ones, and have the advantage of carrying no net charge and can therefore be expected to exhibit no electroendosmosis. PMID- 1935875 TI - Evaluation of membranes used for electroblotting of proteins for direct automated microsequencing. AB - Protein purification and characterisation have been age-old problems for the biochemist. A new era has arisen with the advent of one- and two-dimensional gel electrophoresis and high sensitivity automated protein microsequencing. These two tools along with electroblotting have made it possible to separate and analyse complex protein mixtures. We studied six different membranes compatible with Edman degradation chemistry to determine their efficiencies at binding proteins electroblotted from one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Their overall blotting-sequencing properties were also evaluated. We found that the polyvinylidene difluoride-based membranes out performed the glass-based and polypropylene-based membranes under our selected experimental conditions. The problems associated with electroblotting and microsequencing are discussed. PMID- 1935876 TI - Identification of human esterase D subunits from the homodimeric and heterodimeric forms of five phenotypes by a new two-dimensional isoelectric focusing method. AB - A new two-dimensional isoelectric focusing method was developed to identify the human esterase D (EsD) subunits from the homodimeric and heterodimeric forms of five EsD phenotypes. EsD polymorphism was also analyzed by one-dimensional isoelectric focusing under reducing and mild denaturing conditions to study the influence of dithiothreitol and low concentrations of urea on the focusing pattern of the EsD dimers. PMID- 1935877 TI - Observation of orientation and relaxation of protein-sodium dodecyl sulfate complexes during pulsed intermittent field polyacrylamide gel electrophoresis. AB - Polyacrylamide gel electrophoresis (PAGE) of proteins denatured with SDS (sodium dodecyl sulfate) has been used successfully to separate proteins according to their molecular mass. In spite of the extensive use of this technique, the motion of the protein-SDS complex in a polyacrylamide gel is still not understood. Here we report on the observation of the orientation (in the field direction) and relaxation of protein-SDS complexes during pulsed intermittent field PAGE experiments. The results give an indication of the stiffness of the molecules and may be useful for the development of a technique to improve the separation of large proteins using pulsed electric fields. PMID- 1935878 TI - A miniaturized electrode configuration for isoelectric focusing. AB - An electrode configuration is described which allows fast isoelectric focusing (IEF) with conventional IEF systems. The equipment, which can be fixed on the cooling plate of a conventional IEF system, consists of a base plate on which flappable electrode holders are fastened. The handling is simple and needs only little time. Graphite rods are used as electrodes, thus avoiding the use of buffer strips. Samples are applied with special applicator strips--permitting the analysis of up to 19 samples on a 50 x 40 mm polyacrylamide gel and up to 44 samples on a 100 x 70 mm gel. Only 30 min are needed for one IEF run. PMID- 1935879 TI - Description of a new variant in the glutamate-oxaloacetate transaminase system by thin-layer agarose gel isoelectric focusing. AB - Thin-layer isoelectric focusing in agarose within the pH range of 4.0-6.5 has shown a high resolution of the soluble cytoplasmic glutamate-oxaloacetate transaminase (GOT1) banding pattern. The complex pattern of the common GOT1 phenotype consists of eight bands with different intensities. A genetic variant of GOT1, which has been designated GOT1 Mexico, could tentatively be identified. PMID- 1935880 TI - A rapid (less than 10 minute) electrophoresis method for identification of wheat varieties. AB - Conventional procedures for electrophoretic identification of grain samples according to variety are too slow to permit checking at the time of delivery. The method described permits electrophoretic identification within an hour. It involves extraction of gliadin proteins from crushed grain with 6% urea solution or ethylene glycol, cathodic electrophoresis for 9 min at 300 V in a Micrograd gel (MG 315 from Gradipore Ltd, Sydney, Australia) using sodium lactate buffer (pH 3.1), and staining in Gradipore (at about 50 degrees C). Distinction between a set of Australian varieties was similar to that obtainable with the Australian Standard Procedure. PMID- 1935881 TI - High resolution electrophoresis of soybean seed isoesterases. AB - A modified discontinuous buffer system for vertical polyacrylamide electrophoresis was developed with large changes in component concentration from the original Tris-HCl/Tris-glycine system of the Ornstein-Davis type. The new buffer system is able to resolve the fast soybean seed isoesterases crucial for cultivar discrimination. A higher number of anodic bands is obtained in comparison with separations under standard conditions. A "gelating boundary", resulting from the aggregation of seed proteins, is retarded and does not migrate out of the upper stacking gel. The same buffer modification is also beneficial to the separation of native seed proteins. PMID- 1935882 TI - Integrated displays and the perception of graphical data. AB - Three experiments are presented that apply a principle of compatibility of proximity to the perception of graphical data. These experiments demonstrate that the merits and costs of integral displays relative to separable displays depend in part on the task being performed. Experiment 1 employs a data extrapolation task in which information must be integrated. Here an integral display is found to be superior to a separable display. Experiment 2 employed a data perception task that requires focused attention. This reveals superior performance with separable displays. Experiment 3 employed a multiple cue judgement task in which information integration could be manipulated. Data from Experiment 3 were analysed using the Brunswick lens procedures, and indicated that knowledge of the task structure was influenced by the display type. When selective attention was required, knowledge of the task was superior with separable displays. The results are discussed with reference to the principle of compatibility of proximity, and the implications of the results for the perception of scientific data are noted. PMID- 1935883 TI - Effects of monitoring under high and low taskload on detection of flashing and coloured radar targets. AB - While midair collisions between aircraft are extremely rare occurrences, 'near midair' incidents are more common. The present study sought to evaluate the gains in conspicuity that might be realized if flashing or colour were added as redundant cues to indicate the presence of unexpected, non-tracked aircraft entering controlled airspace, and to examine the extent to which increased taskload and fatigue might influence the expected gains. Sixty-four subjects monitored a simulated air traffic control task over a 2 h period for possible conflict situations (their primary task) under either high or low primary taskload conditions. They also monitored for occasional intrusions by light aircraft identifiable on the basis of target shape alone or with colour and/or flashing added as redundant cues. Flashing as a redundant cue was found to be superior to colour in all aspects tested; unlike colour, detection of flashing targets was unaffected by screen location and by changes in primary taskload. Flashing was also least affected by monitoring fatigue. It was concluded that the superiority of flashing over colour in attracting attention to objects in a display must be weighed against its possible potential for distraction. A practical means of accomplishing this in operational situations is through the use of touch sensitive displays to both acknowledge/confirm target location and to deactivate flashing. PMID- 1935884 TI - Cognitive representations, control, and understanding of complex systems: a field study focusing on components of users' mental models and expert/novice differences. AB - Users' mental models of systems are frequently asserted to be important in their interactions with those systems. Although there are few explicit definitions of mental models in the literature, mental models are assumed to be important and researchers have seemed to accept and understand the concept intuitively. In our research, we have extracted three themes from the definitions of mental models including: (1) the relations among features or components of a system; (2) the capability of the mental model to aid in the control of the system; and (3) the capability of the mental model to enhance the user's understanding of the system. The relationships among the components of users' mental models, including procedural and declarative knowledge, perceptions of the use of system features, and the relations among the similarity of use of system features, were investigated in a field study. Trained and untrained novice users of a new business phone system rated the similarity of use of nine standard features on the phone. These ratings were used to derive cognitive representations of the relations among the system features. Users' ratings of features on univariate scales about the use of the features and scores obtained on a test of procedural knowledge were related to these representations. The two novice groups' mental models were similar except for the perception of one feature; it was more accurately depicted in the trained users' representation than those who did not attend a training programme. Two types of experts' similarity of use ratings were evaluated to determine an 'appropriate' representation of the use of the system features; this was then compared to the novices'. This comparison suggested that there were deficiencies in the mental models of novices. Designing training programmes and instructional aids for systems using the discrepancies between novices' and experts' mental models are discussed. PMID- 1935885 TI - Third World continuing medical education with hypertext: the Liverpool Anaemia Guide System. PMID- 1935886 TI - Remembering about documents: memory for appearance, format, and location. AB - If we remember the visual appearance of documents, and other attributes such as location, then a number of new information management strategies become possible candidates for application in the design of filing systems. This paper describes a number of experiments aimed at investigating aspects of memory for documents in office settings. There is no evidence, as has previously been suggested, that automatic encoding for appearance or location of documents occurs at significant levels. The results of these experiments are more consistent with the view that visual and spatial attributes of documents are remembered in proportion to the attention paid to them when the documents are handled. The experiments also illustrate the sensitivity of this principle to the context in which subjects use documents. It is apparent that office tasks vary considerably in the extent to which subjects must pay attention to the visual and locational attributes of the documents handled. The consequences for the design of filing systems is discussed in terms of what methods for storage and retrieval can usefully be built into the design of systems. PMID- 1935887 TI - Simulation as a tool in the measurement of human performance. AB - The paper outlines and discusses issues in the present-day development and application of simulations of complex tasks. It is noted that this development is observed in basic as well as in applied research, resulting in a trend away from the investigation of elementary properties of human functioning in favour of the analysis of complete tasks. One of the problems in simulation concerns appropriate output measures (section 2). Some recent sophisticated measures of performance are derivatives of more elementary measures of time and accuracy, but they still facilitate new insights into the measurement of performance. In addition, recent views are discussed of verbal reports as potential measures of cognitive skills. It is noted that the issue of performance measurement has been severely neglected and ignored in many applications of simulators. The paper also focuses on theoretical models (section 3). It is concluded that models for complete tasks face the problem of excessive complexity, thus inhibiting detailed parametric analysis. In this respect the analysis of elementary properties has a clear advantage. A strategy of back-to-back experimentation, originally proposed by Gopher and Sanders (1984), is reiterated and an example of a back-to-back study is described. Section 4 of the paper is devoted to the issue of validation with major emphasis on the possibilities and limitations of the transfer paradigm and the measurement of direct correspondence. The final section (5) is devoted to some selective remarks about the three main areas where simulators are applied, namely training, equipment design, and personnel assessment. The paper ends by summarizing some emerging trends and issues for future research. PMID- 1935888 TI - Dances with sigmas. PMID- 1935889 TI - The membrane spanning domain of beta-1,4-galactosyltransferase specifies trans Golgi localization. AB - Chimeric cDNAs were constructed so as to generate hybrid proteins in which different parts of the N-terminal domain of the human invariant chain were replaced by equivalent sequences from the trans Golgi resident enzyme, beta-1,4 galactosyltransferase. The cytoplasmic and membrane spanning domains of galactosyltransferase were found to be sufficient to retain all of the hybrid invariant chain in trans Golgi cisternae as judged by indirect immunofluorescence, treatment with brefeldin A and immuno-electron microscopy. As few as ten amino acids corresponding to the lumenal half of the membrane spanning domain of the Golgi enzyme sufficed to localize most of the hybrid invariant chain to the trans cisternae. A cytoplasmic domain was necessary for complete retention as assessed by flow cytofluorometry but could be provided either by galactosyltransferase or by invariant chain. This suggests that the cytoplasmic domain plays a role accessory to the membrane spanning domain, the latter mediating compartmental specificity. PMID- 1935890 TI - Sequences within and adjacent to the transmembrane segment of alpha-2,6 sialyltransferase specify Golgi retention. AB - The glycosyltransferase alpha-2,6-sialyltransferase (ST) is a Type II membrane protein localized to the Golgi apparatus. The first 44 amino acids of this protein were able to specify Golgi retention of a fused marker protein, lysozyme. This section of ST contains a transmembrane segment which serves as a non-cleaved signal anchor. When lysozyme was fused to an equivalent region of a cell surface protein it now appeared on the cell surface. Analysis of chimeras between the two proteins revealed that the transmembrane segment of ST specifies Golgi retention. Furthermore, altering this segment in full-length ST results in the protein accumulating on the cell surface. However, the retaining effect of the transmembrane domain of ST is augmented by the presence of adjacent lumenal and cytoplasmic sequences from ST. If these sequences are spaced apart by a transmembrane domain of the same length as that of ST they too can specify Golgi retention. Thus retention in the Golgi of ST appears to involve recognition of an extended region of the protein within and on both sides of the bilayer. PMID- 1935891 TI - Newly synthesized synaptophysin is transported to synaptic-like microvesicles via constitutive secretory vesicles and the plasma membrane. AB - The biogenesis of synaptic-like microvesicles (SLMVs) in neuroendocrine cells was investigated by studying the traffic of newly synthesized synaptophysin to SLMVs in PC12 cells. Synaptophysin was found to be sulfated, which facilitated the determination of its exit route from the trans-Golgi network (TGN). Virtually all [35S]sulfate-labeled synaptophysin was found to leave the TGN in vesicles which were indistinguishable from constitutive secretory vesicles but distinct from immature secretory granules and SLMVs. [35S]sulfate-labeled synaptophysin was rapidly transported from the TGN to the cell surface, with a t1/2 of approximately 10 min in resting cells. After arrival at the cell surface, [35S]sulfate-labeled synaptophysin cycled for at least 1 h between the plasma membrane and an intracellular compartment likely to be the early endosome. Up to approximately 40% of the [35S]sulfate-labeled synaptophysin eventually (after 3 h and later) reached SLMVs, which could be distinguished from the other post-TGN compartments by their lower buoyant density in a sucrose gradient and their selective inclusion upon permeation chromatography using a controlled-pore glass column. Our results suggest that newly synthesized membrane proteins of SLMVs in neuroendocrine cells, and possibly of small synaptic vesicles in neurons, reach these organelles via the TGN----plasma membrane----early endosome. PMID- 1935892 TI - Cutting and closing without recombination in V(D)J joining. AB - Open and shut junctions are rare (V(D)J joining products in which site-specific recognition, cleavage and re-ligation of joining signals has been uncoupled from recombination. Here, we investigate the relationship of opening and shutting to recombination in two ways. First, we have tested a series of substrates containing one or two joining signals in an in vivo assay. Opening and shutting can be readily observed in substrates that have only one consensus joining signal. Thus, unlike recombination, the majority of open and shut events do not require interactions between two canonical joining signals. Next we examined two signal substrates to investigate the effect of signal proximity on the frequency of dual open and shut events. These experiments indicate that at least some of the time opening and shutting can be a two-signal transaction. Together these results point to two mechanistically related, but distinct origins for open and shut joining events. In one case, cutting and closing may occur without interaction between two signals. In the other, we suggest that interaction of a canonical signal with 'cryptic' signal-like elements whose sequence is extensively diverged from canonical signals, may bias the V(D)J recombination machinery towards opening and shutting rather than recombination. Open and shut operations could in this way provide a means whereby mistakes in target recognition by the V(D)J recombination machinery produce a non-recombinant outcome, avoiding deleterious chromosomal rearrangements in lymphoid tissues. PMID- 1935893 TI - Physical map of the 3' region of the human immunoglobulin heavy chain locus: clustering of autoantibody-related variable segments in one haplotype. AB - We have constructed the physical map of the 3' region of the human immunoglobulin heavy chain variable region (VH) genes. DNA segments extending to 200 kb upstream of the JH segment were isolated in two YAC clones. Five VH segments were identified in this region in the 5' to 3' order, V(II-5), V(IV-4), V(I-3), V(I 2), and V(VI-1) segments which were all structurally normal and orientated in the same direction as the JH segments. From DNA of a different cell line we have isolated a cosmid contig containing the same DNA region which has extraordinary polymorphism. The YAC and cosmid DNAs were called haplotypes A and B, respectively. Haplotype B contained an additional VH-I segment (V(I-4.1b)) between the V(II-5) and V(IV-4) segments. V(I-4.1b) segment is almost identical to a previously published VH sequence encoding a rheumatoid factor. Another VH segment in the B haplotype (V(I-3b)) corresponding to the V(I-3) segment also showed 99.7% nucleotide sequence homology with an anti-DNA autoantibody VH sequence. However, none of the VH sequences in haplotype A showed such strong homology with autoantibody VH sequences. The results suggest that VH haplotypes may have linkage with autoantibody production. PMID- 1935894 TI - Axon-regulated expression of a Schwann cell transcript that is homologous to a 'growth arrest-specific' gene. AB - We have isolated a 1.8 kb cDNA (pCD25) clone that encodes a transcript that is differentially expressed during nerve regeneration. Nucleotide sequence comparison indicates 89.6% homology with the recently identified murine 'growth arrest-specific' gene gas3. The open reading frame of the CD25 transcript predicts a 17 kDa protein with four putative transmembrane regions. Steady-state levels of the CD25 mRNA are very much higher in sciatic nerve than in other tissues, and expression in sciatic nerve is confined to Schwann cells. Following nerve injury, the transcript levels rapidly declined in nerve segments distal to the site of lesion, but recovered upon nerve regeneration. In contrast, in distal stumps of permanently transected nerves, the mRNA level remained very low. Substantial amounts of the mRNA could be reinduced only upon anastomosis of these interrupted nerve stumps. Re-induction of the mRNA followed the elongation of regenerating axons through the distal nerve segment. Our data indicate that axons regulate expression of the CD25 mRNA in Schwann cells, and suggest that the CD25 protein functions during Schwann cell growth and differentiation. PMID- 1935895 TI - Carboxyl methylation and farnesylation of transducin gamma-subunit synergistically enhance its coupling with metarhodopsin II. AB - A heterotrimeric G-protein in vertebrate photoreceptor cells is called transducin (T alpha beta gamma), whose gamma-subunit is a mixture of two components, T gamma 1 and T gamma-2. T gamma-2 is S-farnesylated and partly carboxyl methylated at the C-terminal cysteine residue, whereas T gamma-1 lacks the modified cysteine residue. To elucidate the physiological significance of the double modifications in T gamma, we established a simple chromatographic procedure to isolate T gamma 1, methylated T gamma-2 and non-methylated T gamma-2 on a reversed phase column. Taking advantage of the high and reproducible yield of T gamma from the column, we analyzed the composition of T gamma subspecies in the T alpha-T beta gamma complex which did not bind with transducin-depleted rod outer segment membranes containing metarhodopsin II. The binding of T alpha-T beta gamma with the membranes was shown to require the S-farnesylated cysteine residue of T gamma, whose methylation further enhanced the binding. This synergistic effect was not evident when T alpha was either absent or converted to the GTP-bound form which is known to dissociate from T beta gamma. Thus we concluded that a formation of the ternary complex, T alpha-T beta gamma-metarhodopsin II, is enhanced by the farnesylation and methylation of T gamma. This suggests that the double modifications provide most efficient signal transduction in photoreceptor cells. PMID- 1935896 TI - The N-Myc oncoprotein is associated in vivo with the phosphoprotein Max(p20/22) in human neuroblastoma cells. AB - Proteins encoded by the proto-oncogenes c-myc, L-myc, and N-myc contain at their carboxy-terminus a tripartite segment comprising a basic DNA binding region (BR), a helix-loop-helix (HLH) and a leucine zipper motif (Zip), that are believed to be involved in DNA binding and protein-protein interaction. The N-Myc oncoprotein is overexpressed in certain human tumors that share neuroectodermal features due to amplification of the N-myc gene. Using a monoclonal antibody directed against an N-terminal epitope of the N-Myc protein in immunoprecipitations performed with extracts of neuroblastoma cells, two nuclear phosphoprotein, p20/22, forming a hetero-oligomeric complex with N-Myc are identified. Both proteins are phosphorylated by casein kinase II in vitro. By partial proteolytic maps we show that p20 and p22 are structurally related to each other and that p20 is identical with Max, a recently described in vitro binding partner of myc proteins. Time course experiments show the presence of the complex in cellular extracts immunoprecipitated within a 5 min interval after the preparation of the cell extract. While the expression of N-myc is restricted, expression of both Max(p20/22) and the murine homolog Myn(p20/22) was observed in cells of diverse human and murine embryonal lineages as detected by heterologous complex formation. By introduction of expression vectors containing the wild type N-myc gene or N-myc genes with in frame deletions or point mutations into recipient cells and subsequent immunoprecipitation of the resulting N-Myc proteins we show that the HLH-Zip region is essential to the formation of the N-Myc-p20/22 complex. PMID- 1935897 TI - In vitro binding of the asialoglycoprotein receptor to the beta adaptin of plasma membrane coated vesicles. AB - The asialoglycoprotein (ASGP) receptor was used to probe total clathrin-coated vesicle proteins and purified adaptor proteins (APs) which had been fractionated by gel electrophoresis and transferred to nitrocellulose. The receptor was found to interact with proteins of approximately 100 kDa. The cytoplasmic domain of the ASGP receptor subunit H1 fused to dihydrofolate reductase competed for receptor binding to the 100 kDa polypeptide in the plasma membrane-type AP complexes (AP 2). A fusion protein containing the cytoplasmic domain of the endocytic mutant haemagglutinin HA-Y543 also competed, but a protein with the wild-type haemagglutinin sequence did not. This indicates that the observed interaction is specific for the cytoplasmic domain of the receptor and involves the tyrosine signal for endocytosis. When fractionated by gel electrophoresis in the presence of urea, the ASGP receptor binding polypeptide displayed a characteristic shift in electrophoretic mobility identifying it as the beta adaptin. Partial proteolysis of the AP-2 preparation followed by the receptor binding assay revealed that the aminoterminal domain of the beta adaptin contains the binding site for receptors. PMID- 1935898 TI - Tyrosine phosphorylation of a yeast 40 kDa protein occurs in response to mating pheromone. AB - Tyrosine phosphorylation of proteins in the yeast Saccharomyces cerevisiae has been examined following exposure to the mating pheromone alpha-factor. When a cells are treated with alpha-factor a protein of approximately 40 kDa molecular weight is tyrosine phosphorylated. This tyrosine phosphorylation response requires an intact signal transduction pathway, is not restricted to a short interval of the cell division cycle, and requires protein synthesis for its maximal accumulation. Mating competent fus3 deletion strains fail to elaborate the phosphotyrosine response. The possibility that FUS3 encodes the 40 kDa protein is discussed. PMID- 1935899 TI - Mutational analysis of the yeast a-factor transporter STE6, a member of the ATP binding cassette (ABC) protein superfamily. AB - STE6, the yeast a-factor transporter, is a member of the ATP binding cassette protein superfamily, which also includes the mammalian multidrug resistance protein and the cystic fibrosis gene product. These proteins contain two homologous halves, each with six membrane spanning segments and a predicted ATP nucleotide binding domain. To assess the importance of the two halves of STE6, and to examine the functional significance of residues conserved among members of the ATP binding cassette superfamily, we introduced mutations into the nucleotide binding domains of STE6. Our analysis demonstrates that both halves of STE6 are critical for function and that some, but not all, mutations analogous to those known to result in cystic fibrosis impair STE6 activity. To examine further the functional contribution of each half of the STE6 protein, we severed the STE6 coding sequence and expressed the two halves of the transporter as separate polypeptides. Whereas 'half-molecules' are unable to provide transport function individually, co-expression of both half-molecules in the same cell leads to functional reconstitution of STE6-mediated a-factor transport. PMID- 1935900 TI - The CCAAT/enhancer binding protein and its role in adipocyte differentiation: evidence for direct involvement in terminal adipocyte development. AB - During the course of differentiation of preadipocytes into adipocytes, several differentiation-linked genes are activated synchronously with morphological changes. To follow this process we have used 3T3-F442A cells, known to undergo adipocyte conversion with high frequency. Accumulation of lipid droplets in the cytoplasm constitutes an easily visualized sign of the terminally differentiated phenotype. In this report we demonstrate that expression of the CCAAT/enhancer binding protein (C/EBP) is an important factor in determining the ability to accumulate lipid droplets in terminally differentiated adipocytes. In one experiment we can suppress C/EBP expression through administration of hydrocortisone to differentiating 3T3-F442A cells, which is accompanied by an inability of the cells to accumulate lipid. In another experiment a C/EBP antisense expression vector has been stably introduced into 3T3-F442A cells and as compared with control cells, a 62% decrease of C/EBP mRNA (p less than 0.01) is demonstrated. This decrease of C/EBP mRNA is accompanied by a change in cellular morphology characterized by a reduced ability to form lipid droplets. We can also demonstrate a correlation between the degree of reduction of C/EBP mRNA and the amount of lipid present in the cells. These findings strongly support the view that C/EBP is a necessary component of terminal adipocyte differentiation. PMID- 1935901 TI - Binding of the HTLV-I Tax1 transactivator to the inducible 21 bp enhancer is mediated by the cellular factor HEB1. AB - Transcription driven by the HTLV-I promoter is strongly activated by the viral transactivator protein Tax1. This effect is mediated via a 21 bp sequence which is imperfectly repeated three times in the viral promoter. We showed previously that a single 21 bp copy exhibits a strong Tax1-inducible enhancer activity and is able to bind different cellular proteins, namely ATF, HEB1 and HEB2. We have further investigated the molecular mechanism involved in the Tax1 induction of the 21 bp motif's enhancer activity by analysing Tax1 interaction with this DNA sequence. For this purpose a HeLa cell line constitutively expressing a functional Tax1 protein was established and nuclear extracts of these cells were used to perform a DNA affinity precipitation assay. This experimental approach allowed us to show that Tax1 specifically binds to the 21 bp motif. The same sequence elements of the 21 bp motif are required both for Tax1 binding and for Tax1-induced enhancer activity. Chromatographic fractionation of the HeLa tax nuclear extract showed that the binding is indirect and is mediated by the cellular factor HEB 1. PMID- 1935902 TI - The p65 subunit is responsible for the strong transcription activating potential of NF-kappa B. AB - The nuclear form of the NF-kappa B transcription factor binds to DNA as a heterodimer of a 50 kDa (p50) and 65 kDa (p65) polypeptide. The two polypeptides are encoded by different genes but share a long region of homology, the NRD motif, encompassing domains required for DNA binding and dimerization. In this study we have analysed the contribution of the two subunits to the strong transactivating potential of NF-kappa B. Transient expression of the p65 subunit alone resulted in a potent transactivation of a CAT reporter construct under the control of two NF-kappa B binding sites in monkey COS and mouse L cells. The strongly DNA binding p50 subunit showed only very weak, if any, induction of gene expression. Co-expression of p50 suppressed the transactivation by p65 presumably by competitive DNA binding of transcriptionally inactive p50 dimers (KBF1). Fusion of p65 sequences to DNA binding domain of the yeast GAL4 transcription factor allowed detection of the principal transactivation domain of p65 (TA1) in the C-terminal 30 amino acid sequence. TA1 is likely to adopt an amphipathic alpha-helical structure which clusters serine residues on the hydrophilic surface, a structural feature conserved between human, mouse and Xenopus p65. The unique C-terminal third of p65 contained at least one more activation domain, TA2, within a 90 amino acid sequence directly adjacent to TA1. In two mammalian cell lines, TA1 and TA2 acted separately, while in an insect cell line, the two domains were inactive after their separation. Our study suggests that the p50 subunit in NF-kappa B might only serve a helper function in DNA binding whereas the p65 subunit is responsible for initiating transcription. Homodimers of p50 seem to have the potential of down-regulating kappa B-specific gene expression. PMID- 1935904 TI - Nucleocytoplasmic shuttling of the progesterone receptor. AB - The nuclear localization of the progesterone receptor is mediated by two signal sequences: one is constitutive and lies in the hinge region (between the DNA and steroid binding domains), the other is hormone dependent and is localized in the second zinc finger of the DNA binding domain. The use of various inhibitors of energy synthesis in cells expressing permanently or transiently the wild-type receptor or a receptor mutated within the nuclear localization signals, demonstrated that the nuclear residency of the receptor reflects a dynamic situation: the receptor diffusing into the cytoplasm and being constantly and actively transported back into the nucleus. The existence of this nucleo cytoplasmic shuttle mechanism was confirmed by receptor transfer from one nucleus to the other in heterokaryons. Preliminary evidence was obtained, using oestrogen receptor, that this phenomenon may be of general significance for steroid receptors. PMID- 1935903 TI - Cell-specific inhibitory and stimulatory effects of Fos and Jun on transcription activation by nuclear receptors. AB - We investigated the effect of c-Fos and/or c-Jun co-expression on transcription activation by the progesterone (PR), glucocorticoid (GR) or androgen (AR) receptors using three different reporter genes and four different cell lines. We found that c-Fos could only inhibit, while c-Jun could either inhibit or further stimulate receptor-induced transcription. All these effects were receptor, promoter, and cell type specific, and, importantly, the steroid receptors had non reciprocal effects on the transactivation ability of c-Jun in the presence or absence of c-Fos. Collectively, these results argue against heterodimer formation as a mechanism to explain the phenomena. Transactivation by the endogenous PR in T47D cells could be inhibited by increasing the intracellular c-Fos level with forskolin as well as by co-expressing c-Fos; no such effect was seen in MCF-7 cells. The inhibition by c-Fos of PR-induced transcription involves a competitive mechanism, which requires the presence of the intact c-Fos leucine zipper and is directed mainly at the transcription activation function (TAF) located in the PR and GR hormone binding domains (TAF-2). However, the co-expression of c-Fos did not alter the 'squelching/transcriptional interference' by the PR of estrogen receptor (ER)-induced transcription. Multiple mechanisms are discussed which may be involved in the crosstalk between the two signal transduction pathways. PMID- 1935906 TI - Intramolecular base pairing between the nematode spliced leader and its 5' splice site is not essential for trans-splicing in vitro. AB - The spliced leader RNAs of both trypanosomes and nematodes can form similar secondary structures where the trans-splice donor site is involved in intramolecular base pairing with the spliced leader sequence. It has been proposed that this base pairing could serve to activate autonomously the SL RNA splice donor site. Here, we have examined exon requirements for trans-splicing in a nematode cell free system. Complete disruption of secondary structure interactions at and around the trans-splice donor site did not affect the ability of the SL RNA to function in trans-splicing. In addition, the highly conserved 22 nt sequence could be productively replaced by artificial exons ranging in size from 2 to 246 nucleotides. These results reinforce the view that the 'intron' portion of the SL RNA functions as an independent Sm snRNP whose role is to deliver exon sequences to the trans-spliceosome. PMID- 1935905 TI - Trypanosoma brucei glycosomal glyceraldehyde-3-phosphate dehydrogenase genes are stage-regulated at the transcriptional level. AB - Regions 5' of the glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) gene from Trypanosoma brucei were tested for their ability to promote chloramphenicol acetyl-transferase (CAT) expression on reintroduction by electroporation into the parasite. Deletion analysis mapped the gGAPDH promoter to within 403 nts of the start of translation. A transcription initiation site was mapped at around -190 nts from the ATG start codon by RNase protection and by primer extension. The higher expression of gGAPDH in bloodstream T. brucei, compared to procyclic (insect) forms, was largely attributed to differences in promoter activity. The gGAPDH promoter gave rise to relatively high CAT signals upon transfection into bloodstream T. brucei and relatively low signals in procyclic T. brucei, compared with levels resulting from transfection with the procyclic acidic repetitive protein (PARP) promoter. In addition, RNase protection data showed a higher level of gGAPDH primary transcripts in bloodstream. T. brucei. The PARP mini-exon addition region abolished transient CAT expression directed by either the gGAPDH or PARP promoters in bloodstream T. brucei implying that transplicing can be a point of stage-specific gene regulation. PMID- 1935908 TI - Translation of a polycistronic mRNA in the presence of the cauliflower mosaic virus transactivator protein. AB - Polycistronic mRNAs containing an upstream beta-glucuronidase (GUS) and a downstream chloramphenicol acetyltransferase (CAT) reporter open reading frame (ORF) were expressed in transfected plant protoplasts. CAT expression could be strongly induced by coexpression of the cauliflower mosaic virus encoded translation transactivator. Transactivation was abolished when an upstream ORF overlapped the CAT ORF for a long distance. No specific sequence elements were required for transactivation but the presence of a short ORF upstream of the GUS ORF strongly enhanced the process. The inhibitory effect of additional presumed stem structures inserted into various regions of the reporter mRNAs indicates that both ORFs are translated by ribosomes that associate with the RNA at the 5' end and reach the ORFs by a linear migration mechanism. PMID- 1935907 TI - Requirement of a polypyrimidine tract for trans-splicing in trypanosomes: discriminating the PARP promoter from the immediately adjacent 3' splice acceptor site. AB - We studied sequence requirements for trans-splicing at the 3' splice acceptor site of a procyclic acidic repetitive protein (PARP) coding gene in trypanosomes. In transient CAT transfection assays with linker scanning (LS) mutants in a PARP promoter--3' splice acceptor site--CAT construct, minor differences in the sequence composition of the polypyrimidine tract (nt -36 to -5 with respect to the 3' splice acceptor site) severely affected the CAT activity. Analysis of steady-state CAT RNA in stably transformed trypanosomes revealed that the LS mutations had indeed affected the pre-mRNA splicing efficiency. The data indicate that mini-exon addition is not required simply for maturation of polycistronic pre-mRNA but is also essential for the generation of functional mRNA from monocistronic genes, since unspliced monocistronic pre-mRNA did not accumulate or allow synthesis of CAT. We postulate that mini-exon addition at polycistronically transcribed genes, which can have drastically different polypyrimidine tracts at each of their 3' splice acceptor sites, can occur with different efficiencies for each gene of the array thus affecting mRNA abundance. PMID- 1935909 TI - AppppA binds to several proteins in Escherichia coli, including the heat shock and oxidative stress proteins DnaK, GroEL, E89, C45 and C40. AB - The dinucleotide AppppA (5',5'''-P1, P4-diadenosine tetraphosphate) is rapidly synthesized in cells exposed to heat stress or oxidative stress. Stress-induced AppppA accumulation has been observed in all cell types studied to date. In order to study the function(s) of AppppA, we created a mutation in the Escherichia coli gene that encodes the sole AppppN hydrolase (apaH). High levels of AppppA have subsequently been shown to affect many cellular processes, including expression of catabolite repressible genes and the ability to survive starvation, oxidative stress and near-UV irradiation. Nevertheless, the precise role of AppppA remains undefined. In order to better understand the mechanism by which AppppA exerts its effects, we attempted to determine which proteins bind to AppppA by synthesizing (alpha'-32P) 8-N3AppppA for use in photocrosslinking experiments with extract derived from cells with different genetic backgrounds and exposed to various stress conditions. We report here that several E. coli proteins bind AppppA, including the heat shock and oxidative stress proteins DnaK, GroEL, E89, C45 and C40. In addition, we show that apaH mutants, which have high basal levels of AppppA, are hypersensitive to killing by heat. PMID- 1935910 TI - Complementation of DNA repair in xeroderma pigmentosum group A cell extracts by a protein with affinity for damaged DNA. AB - Complementation group A of xeroderma pigmentosum (XP) represents one of the most prevalent and serious forms of this cancer-prone disorder. Because of a marked defect in DNA excision repair, cells from individuals with XP-A are hypersensitive to the toxic and mutagenic effects of ultraviolet light and many chemical agents. We report here the isolation of the XP-A DNA repair protein by complementation of cell extracts from a repair-defective human XP-A cell line. XP A protein purified from calf thymus migrates on denaturing gel electrophoresis as a doublet of 40 and 42 kilodaltons. The XP-A protein binds preferentially to ultraviolet light-irradiated DNA, with a preference for damaged over nondamaged nucleotides of approximately 10(3). This strongly suggests that the XP-A protein plays a direct role in the recognition of and incision at lesions in DNA. We further show that this protein corresponds to the product encoded by a recently isolated gene that can restore excision repair to XP-A cells. Thus, excision repair of plasmid DNA by cell extracts sufficiently resembles genomic repair in cells to reveal accurately the repair defect in an inherited disease. The general approach described here can be extended to the identification and isolation of other human DNA repair proteins. PMID- 1935911 TI - Rolling circle replication of DNA in yeast mitochondria. AB - The conformation of mitochondrial DNA (mtDNA) from yeasts has been examined by pulsed field gel electrophoresis and electron microscopy. The majority of mtDNA from Candida (Torulopsis) glabrata (mtDNA unit size, 19 kb) exists as linear molecules ranging in size from 50 to 150 kb or 2-7 genome units. A small proportion of mtDNA is present as supercoiled or relaxed circular molecules. Additional components, detected by electron microscopy, are circular molecules with either single- or double-stranded tails (lariats). The presence of lariats, together with the observation that the majority of mtDNA is linear and 2-7 genome units in length, suggests that replication occurs by a rolling circle mechanism. Replication of mtDNA in other yeasts is thought to occur by the same mechanism. For Saccharomyces cerevisiae, the majority of mtDNA is linear and of heterogeneous length. Furthermore, linear DNA is the chief component of a plasmid, pMK2, when it is located in the mitochondrion of baker's yeast, although only circular DNA is detected when this plasmid occurs in the nucleus. The implications of long linear mtDNA for hypotheses concerning the ploidy paradox and the mechanism of the petite mutation are discussed. PMID- 1935912 TI - Molecular analysis of X-autosome translocations in females with Duchenne muscular dystrophy. AB - To further an understanding of the mechanism of constitutional chromosomal rearrangement, the translocation breakpoints of two X-autosome translocations carried by females with Duchenne or Becker muscular dystrophy have been mapped, cloned and sequenced. Breakpoints were mapped to specific introns within the dystrophin gene and intron sequences spanning the two breakpoints were cloned and used as probes to identify DNA fragments containing the translocation junctions. The junction-containing fragments were cloned after amplification by inverse PCR or single-specific-primer PCR. Sequence through the junctions and the autosomal regions spanning the breakpoints identified the mechanism of rearrangement as non homologous exchange with minor additions or deletions (0-8 nucleotides) at the breakpoints. Paternal origin of these X-autosome translocations, coupled with evidence for non-transmission of X-autosome translocations through male meiosis suggested that the translocations were the result of a post-meiotic rearrangement in spermiogenesis. PMID- 1935915 TI - Endocrine manifestations of systemic disease. PMID- 1935913 TI - Site-directed mutagenesis of the yeast actin gene: a test for actin function in vivo. AB - The yeast Saccharomyces cerevisiae has a single actin gene, ACT1, whose protein product is essential for cell viability. To study the structure-function relationship of this evolutionarily highly conserved protein, we have introduced into the gene several mutations leading to substitutions of amino acids that, by chemical crosslinking experiments, have previously been identified as potential sites for the interaction of actin with several actin-binding proteins and of actin monomers in filaments. The in vitro mutated actin genes were used to replace one chromosomal ACT1 allele in diploid cells. From diploid transformants, haploids that solely depended on mutant actins were isolated and their phenotypic alterations studied. The replacement of the N-terminal acidic residues (Asp2 and Glu4) with valine was functionally neutral. Substitutions of Asp11 led to dominant lethality. Substitutions of Lys191, Lys336, Trp356, Lys373 and Cys374 were without observable effect on cell growth, proliferation and morphology. Deletion of the C-terminal end, Lys-Cys-Phe-COOH, was lethal, whereas successive removal of the C-terminal Phe375 or Cys374 and Phe375 resulted in temperature sensitivity. At the nonpermissive temperature, the mutant cells were characterized by an increase in size, a tendency to lyse and significant alterations of the actin cytoskeleton. PMID- 1935914 TI - Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. AB - We describe a dominant behavioral marker, rol-6(su-1006), and an efficient microinjection procedure which facilitate the recovery of Caenorhabditis elegans transformants. We use these tools to study the mechanism of C.elegans DNA transformation. By injecting mixtures of genetically marked DNA molecules, we show that large extrachromosomal arrays assemble directly from the injected molecules and that homologous recombination drives array assembly. Appropriately placed double-strand breaks stimulated homologous recombination during array formation. Our data indicate that the size of the assembled transgenic structures determines whether or not they will be maintained extrachromosomally or lost. We show that low copy number extrachromosomal transformation can be achieved by adjusting the relative concentration of DNA molecules in the injection mixture. Integration of the injected DNA, though relatively rare, was reproducibly achieved when single-stranded oligonucleotide was co-injected with the double stranded DNA. PMID- 1935916 TI - Ectopic production of calciotropic peptides. AB - Tumors are frequently associated with factors that affect bone cell function and calcium homeostasis. As a result, many patients with cancer develop paraneoplastic syndromes. The commonest is hypercalcemia of malignancy. Other related paraneoplastic syndromes are hypocalcemia, hypophosphatemia, and osteomalacia. PMID- 1935917 TI - Ectopic secretion of neurohypophyseal peptides in patients with malignancy. AB - A great deal of information has been accumulated on the synthesis and release of AVP, oxytocin, and their associated neurophysins under normal circumstances. In 1957, Schwartz and Bartter first described SIAD in patients with lung cancer and postulated that the clinical findings were the results of excessive vasopressin secretion. Tumors have been known since 1964 to produce vasopressin, and small cell (oat cell) carcinoma of the lung is by far the most frequent malignant cause of SIAD. The biosynthetic pathway for the synthesis of AVP and its associated neurophysin (and to a lesser extent, oxytocin and its neurophysin) is well described and is similar if not identical to the synthesis of these peptides in the hypothalamus. However, there is little reliable information on the control of peptide synthesis and release by these tumors. The clinical picture of SIAD is well described and occurs in 20% to 40% of patients with SCCL, although up to 88% of patients with extensive SCCL have elevated circulating levels of one or more neurohypophyseal peptides. This information has led to considerable interest in the use of these peptides as tumor markers for the diagnosis, evaluation, and assessment of therapy in these patients. With the recognition of the high incidence of secretion of neurohypophyseal peptides by SCCL, studies have been initiated to determine the value of radioactive vasopressin neurophysin antibodies in localizing tumors that synthesize these peptides. The studies provide potentially useful information in diagnosing and following patients with SCCL and also offer some promise that radiolabeled antineurophysins could eventually be used to treat these patients. PMID- 1935918 TI - Extrapituitary acromegaly. AB - Acromegaly may result from ectopic production of the hypothalamic peptide, growth hormone releasing hormone (GHRH), or growth hormone (GH) itself. Hypothalamic, carcinoid, and pancreatic tumors account for most of these cases. The pathogenesis, etiology, and diagnosis of acromegaly caused by these nonpituitary tumors is discussed, and an approach to their management is provided. PMID- 1935919 TI - Gonadotropin secretory abnormalities. AB - Normal physiology of puberty and normal GnRH, LH, FSH, and hCG secretion have been reviewed. Systemic disorders can affect the neuroendocrine axis and cause varying degrees of hypogonadism by acting at different levels in the axis. As both hypothalamic abnormalities and intrinsic pituitary abnormalities can cause an abnormal FSH/LH response to GnRH, this test does not distinguish hypothalamic from pituitary mechanisms of hypogonadism. Therefore, only in disorders that have been demonstrated to have a structural pituitary abnormality (e.g., iron or granulomatous infiltration of the gonadotrophs) can we be certain that the disorder has its effect at the level of the pituitary. Abnormalities leading to hypersecretion (both ectopic and eutopic) of gonadotropins have also been described. To date, ectopic production of FSH and LH has not been unequivocally demonstrated. Systemic disorders cause mainly hypogonadism, many of the symptoms of which are reversible with control or cure of the disease. The effect of hypersecretion of gonadotropins on the reproductive system depends on the age at which the tumor (ectopic/eutopic) occurs. PMID- 1935920 TI - Autoimmunity of diabetes. AB - Insulin-dependent diabetes mellitus is associated with a growing number of immune abnormalities. At the time of clinical onset, most patients developing the disease as children or young adults have autoantibodies reactive with islet beta cells. Current autoantibody markers for IDDM are not sufficient to predict the disease in the general population. Studies in first-degree relatives indicate the presence of a subclinical disease characterized by beta cell dysfunction, which may or may not progress to overt IDDM. Although IDDM is genetically linked to certain HLA-DQ class II molecules, it needs to be clarified whether these molecules determine the propensity to react to certain antigens, the failure to maintain tolerance, or the ability to produce disease-associated autoantibodies. Circumstantial evidence suggests that yet another gene outside the HLA complex on chromosome 6 is more important. The interaction with the environment needs to be clarified, and the etiologic role of viruses has not been substantiated. An underlying systemic autoimmune propensity may influence environmental insults and perpetuate islet beta cell destruction. Until these mechanisms are understood, clinicians should periodically check their patients with IDDM for other organ specific as well as non--organ-specific autoimmune diseases. Our understanding of these phenomena is poor, which may explain why clinical trials with immunosuppressive agents have been of limited success. Further studies on the molecular biology of the immune response against islet beta cell-specific antigens are necessary for the development of both predictive tests and novel measures to prevent IDDM. PMID- 1935921 TI - Autoimmune diseases of the adrenal glands, parathyroid glands, gonads, and hypothalamic-pituitary axis. AB - Autoimmunity directed against the adrenal glands, parathyroid glands, gonads, and hypothalamic-pituitary axis can arise in isolation or as part of a polyglandular autoimmune syndrome. Affected patients can be asymptomatic, but they may also suffer significant morbidity or even mortality. Currently, treatment is restricted largely to hormone replacement when end-organ destruction is almost complete. As our understanding of the pathogenesis of autoimmune endocrinopathies improves, it is probable that early patient detection will become practical and trials of protective immunotherapies entertained. PMID- 1935922 TI - Endocrine complications of sarcoidosis. AB - Sarcoidosis is a multisystem disorder of unknown etiology that frequently involves the lymph nodes, lungs, eyes, and skin. The disease can involve any organ system, and noncaseating granulomas are characteristically present. Synthesis of 1,25-dihydroxyvitamin D, the most biologically active form of vitamin D, occurs in granulomatous tissue and may give rise to increases in its concentration in the peripheral circulation and to hypercalcemia and hypercalciuria. Infiltration of endocrine organs also occurs. Involvement of the hypothalamus and pituitary can cause primary polydipsia and disordered regulation of thirst; diabetes insipidus, impaired secretion of anterior pituitary hormones (with clinically apparent hypothyroidism, hypogonadism, hypoadrenalism, or impaired growth), and increases in serum prolactin may also result. Galactorrhea, however, seldom occurs. Involvement of the thyroid and adrenal glands rarely leads to hypofunction. Involvement of the pancreas rarely occurs but does not produce diabetes mellitus. Involvement of the male reproductive system results in epididymitis and hypogonadism, and involvement of the uterus causes abnormalities in menstrual function. PMID- 1935923 TI - Endocrine complications of AIDS and drug addiction. AB - The endocrine and metabolic consequences of illicit drug use and HIV disease are extensive and profound. Both narcotic drug use and AIDS have the capacity to cause clinically significant multiglandular derangements. Admittedly, we were not able to focus as much attention on the less frequently occurring disturbances of calcium, phosphorus, or folate metabolism in HIV disease. Similarly, we reported very little information about the endocrinologic significance of the use of classes of narcotics other than opiates and to a far lesser extent cocaine. Even with these limitations, the spectrum of drug abuse and HIV-related endocrine manifestations discussed previously is quite diverse. Given the pervasive effects of drug abuse on other organ systems, it is not surprising to find expanding interest in the endocrine consequences of narcotic drug use. In fact, the use of these drugs is responsible, in part, for the past and continuing interest in identifying receptors for these agents and similarly structured endogenous ligands. As these investigations proceed, we must appreciate the limitations in translating basic and clinical scientific findings to the clinical setting. Much of the current research does not study street-relevant narcotic doses, does not use research designs involving polydrug use, and does not involve the processes or routes of drug administration used by active narcotic addicts. There is a critical need for more research methods with animal models and clinical study settings that more adequately mimic drug use outside of the laboratory. Our ability to develop appropriate psychopharmaceutical agents to respond to the different faces of drug abuse in the United States will depend on continued progress in the area of neuroendocrinology. With respect to the consequences of HIV disease, the clinical findings of elevated hormonal levels in some endocrine systems are amazing given what one would expect if one postulated direct or indirect destruction by HIV or the opportunistic complications that accompany AIDS. In unraveling this puzzle, careful attention must be given to evaluating the degree to which the clinical or biochemical consequences are due to a direct HIV effect, to an effect of a complicating infection or neoplasm, or to an AIDS related therapeutic intervention. More work is needed also in obtaining histopathologic information to correlate with the biochemical and clinical derangement. In summary, there is a wealth of information demonstrating a wide spectrum of endocrine/metabolic consequences of drug abuse and AIDS. Still, just as many questions remain unanswered. While the exact biologic mechanisms are unclear, many of the biochemical aberrations have clinical relevance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935924 TI - The effect of prostaglandin E1 on local cerebral blood flow during cerebral aneurysm clip ligation. AB - Prostaglandin E1(PGE1) was administered for deliberate hypotension during general anaesthesia in 27 patients undergoing cerebral-aneurysm clip ligation, and the effect of the drug on local cerebral blood flow was studied. Local cerebral blood flow measurements were made using a thermal-gradient blood flowmeter. Control measurements were made immediately before administration of the drug. Local cerebral blood flow was measured 10, 30, 60 and 120 min after starting the drug infusion and 10, 30 and 60 min after discontinuation. The mean blood pressure was reduced significantly by the administration of PGE1. Urine output was increased after commencement of the drug infusion. Local cerebral blood flow did not change. These results suggest that PGE1 may be an appropriate hypotensive drug for use during cerebral-aneurysm clip ligation, because the cerebral blood flow remains within the normal range and the urine output is increased. PMID- 1935925 TI - Atrial and His-Purkinje conduction times during isoflurane anaesthesia in humans. AB - The effect of isoflurane 2.0 MAC on human atrioventricular conduction time was studied. A non-invasive recording system for the detection of His-Purkinje potentials based on signal averaging techniques was used. Recordings were made in 15 patients before and after induction with isoflurane. We were able to measure atrial (P-H) and His-Purkinje (HPS) conduction times in 11 patients. Mean (+/- SEM) P-H conduction time decreased from 101.8 +/- 5.3 to 89.3 +/- 3.3 ms (P less than 0.01). HPS conduction times did not change significantly. Heart rate increased significantly from 86.7 +/- 4.2 to 94.9 +/- 4.7 beats min-1 (P less than 0.05). Systolic blood pressure decreased from 117.3 +/- 4.6 to 94.1 +/- 4.7 mmHg (P less than 0.05). It is concluded that the effects of isoflurane on supraventricular conduction time in humans depend on interactions of several different mechanisms. PMID- 1935926 TI - General anaesthesia for gamete intra-fallopian transfer. AB - A retrospective survey was undertaken of all patients who had gamete intra fallopian transfer (GIFT) under general anaesthesia at this hospital over an 18 month period. Of 47 patients, 21 (44.7%) became pregnant although only 10 (21.3%) proceeded to term. All of those who proceeded to term had had enflurane as part of their general-anaesthetic technique. Although a number of the patients who received halothane became pregnant, none proceeded beyond the second trimester. It would appear that the use of halothane may be inadvisable for general anaesthesia for this procedure. PMID- 1935927 TI - Total intravenous anaesthesia with propofol or etomidate. AB - In combination with fentanyl, propofol was compared with etomidate for total intravenous anaesthesia in 21 women (ASA Grades I-II) admitted for elective hysterectomy. They received either propofol (bolus 1.5 mg kg-1, infusion 9 mg kg 1 h-1 for 10 min thereafter 6 mg kg-1 h-1) or etomidate (bolus 0.10 mg kg-1, infusion 3 mg kg-1 h-1 reduced to 0.6 mg kg-1 h-1). Fentanyl 10 micrograms kg-1 was given for induction followed by an infusion of 30 micrograms kg-1 h-1 for 10 min reduced to 6 micrograms kg-1 h-1 for the first hour and successively reduced over time. Induction was smooth and maintenance easy to manage in both groups. There was no difference in time from end of infusion until extubation, but the time until the patients could report their date of birth was significantly shorter in the propofol group. Nausea and vomiting were more pronounced in the etomidate group, and mental side-effects were only seen after etomidate. After 3 months, more patients in the etomidate group complained of reduced power of concentration. We conclude that total intravenous anaesthesia with either propofol or etomidate is equally easy to manage, but in the recovery situation propofol was advantageous in time and quality. PMID- 1935928 TI - tRNA-like structures. Structure, function and evolutionary significance. PMID- 1935929 TI - Purification and properties of a high-molecular-mass complex between Val-tRNA synthetase and the heavy form of elongation factor 1 from mammalian cells. AB - In extracts of various mammalian tissues obtained in the presence of protease inhibitors Val-tRNA synthetase exists exclusively as a complex with a molecular mass of about 800 kDa. This complex was purified by gel filtration and two HPLC steps and contained five different polypeptides with molecular masses of 140, 50, 50, 40 and 30 kDa. The complex seems to have no tissue or species specificity, because preparations with identical polypeptide composition were obtained by the same method from rabbit liver and reticulocytes, and rat and beef liver. Four low molecular-mass polypeptides were identified by two-dimensional electrophoresis as subunits of the heavy form of elongation factor 1 (EF-1H). The complex possesses the activity of EF-1 in the poly(U)-directed translation system, indicating that EF-1H is an integral part of the complex. Gel filtration of the tissue extracts reveals three different peaks of EF-1 activity, corresponding to EF-1 alpha, EF 1H and the high-molecular-mass complex of Val-tRNA synthetase and EF-1H. All activity of Val-tRNA synthetase and about 25% of EF-1 activity are associated with the complex. Different forms of EF-1 revealed no significant differences in the nucleotide-binding properties, but the complex of Val-tRNA synthetase with EF 1H was 10 times more active in the poly(U)-directed binding of Phe-tRNAPhe to ribosomes than EF-1H. These results strongly suggest that the complex of Val-tRNA synthetase with EF-1H is a novel functionally active individual form of EF-1. PMID- 1935930 TI - Cloning of a cDNA for a new member of the class of fibril-associated collagens with interrupted triple helices. AB - cDNA from embryonic chick skin has been isolated and characterized which encodes a novel member of the FACIT (fibril-associated collagen with interrupted triple helices) group whose other known members are collagen types IX and XII. Nucleotide sequence analysis of the cDNA, combined with characterization of a pepsin-resistant fragment of the protein from embryonic chick skin, demonstrates that the collagen chain is more closely related to the chain of type XII collagen than to those of type IX. It is most similar to a collagen, type XIV, recently identified in bovine skin. It is possible, therefore, that the cDNA codes for a chain of chicken type XIV collagen. From the additional data on molecular structure obtained by sequencing the cDNA, the FACIT family appears to consist of at least two classes of molecules: one of which contains the three chains of type IX collagen, and a second which includes the chains of collagen types XII and XIV. PMID- 1935931 TI - Malic enzyme in human liver. Intracellular distribution, purification and properties of cytosolic isozyme. AB - In human liver, almost 90% of malic enzyme activity is located within the extramitochondrial compartment, and only approximately 10% in the mitochondrial fraction. Extramitochondrial malic enzyme has been isolated from the post mitochondrial supernatant of human liver by (NH4)2SO4 fractionation, chromatography on DEAE-cellulose, ADP-Sepharose-4B and Sephacryl S-300 to apparent homogeneity, as judged from polyacrylamide gel electrophoresis. The specific activity of the purified enzyme was 56 mumol.min-1.mg protein-1, which corresponds to about 10,000-fold purification. The molecular mass of the native enzyme determined by gel filtration is 251 kDa. SDS/polyacrylamide gel electrophoresis showed one polypeptide band of molecular mass 63 kDa. Thus, it appears that the native protein is a tetramer composed of identical-molecular mass subunits. The isoelectric point of the isolated enzyme was 5.65. The enzyme was shown to carboxylate pyruvate with at least the same rate as the forward reaction. The optimum pH for the carboxylation reaction was at pH 7.25 and that for the NADP-linked decarboxylation reaction varied with malate concentration. The Km values determined at pH 7.2 for malate and NADP were 120 microM and 9.2 microM, respectively. The Km values for pyruvate, NADPH and bicarbonate were 5.9 mM, 5.3 microM and 27.9 mM, respectively. The enzyme converted malate to pyruvate (at optimum pH 6.4) in the presence of 10 mM NAD at approximately 40% of the maximum rate with NADP. The Km values for malate and NAD were 0.96 mM and 4.6 mM, respectively. NAD-dependent decarboxylation reaction was not reversible. The purified human liver malic enzyme catalyzed decarboxylation of oxaloacetate and NADPH-linked reduction of pyruvate at about 1.3% and 5.4% of the maximum rate of NADP-linked oxidative decarboxylation of malate, respectively. The results indicate that malic enzyme from human liver exhibits similar properties to the enzyme from animal liver. PMID- 1935932 TI - Conformational change of the haemolymph juvenile-hormone-binding protein from Galleria mellonella (L). AB - A juvenile-hormone-binding protein (juvenile-hormone carrier), isolated from Galleria mellonella haemolymph, was treated with trypsin, chymotrypsin, carboxypeptidase A and subtilisin. Among these enzymes, only subtilisin was able to affect juvenile-hormone-binding activity of this protein. With SDS/PAGE it was shown that juvenile-hormone-binding protein, a 32-kDa peptide, is first slowly converted into a 30-kDa molecule, then into two or three smaller-molecular-mass species (20-25 kDa), which in turn were further digested to small peptides undetectable in PAGE. The 30-kDa peptide has a 2.4-times-higher dissociation constant for juvenile hormone than the native protein. No binding activity was detected for 20-25-kDa peptides. The rate of proteolysis of juvenile-hormone binding protein was decreased by more than twofold in the presence of hormone, however, the overall cleavage pattern was unchanged. Under non-denaturing conditions, free binding-protein molecules could be separated from juvenile hormone-binding-protein complex due to a slower electrophoretic mobility of the complex. As judged from ultracentrifugation and cross-linking experiments, binding of the hormone to its haemolymph carrier does not induce formation of oligomers, but shifts the sedimentation coefficient from 2.30S to 2.71S. It is concluded that juvenile-hormone binding induces a conformational transition of its carrier protein. This hormone-induced change might have a physiological significance for signal transmission. PMID- 1935933 TI - Conformation of [8-arginine]vasopressin and V1 antagonists in dimethyl sulfoxide solution derived from two-dimensional NMR spectroscopy and molecular dynamics simulation. AB - Structural and dynamic properties of [8-arginine]vasopressin and a class of highly potent vasopressin V1 antagonists which contain 3-mercapto-3,3 cyclopentamethylene propionic acid (Mca) in position 1 of the vasopressin sequence have been determined. On the basis of two-dimensional NMR experiments in dimethyl sulfoxide solution, interproton distances were derived according to which model conformations were built and refined using molecular dynamics simulations. The conformation of vasopressin and the V1 antagonists differ mainly in the region of the mutated residue. The antagonistic property was found to be related to an inversed chirality of the disulfide bridge. In all investigated molecules, characteristic beta-turn structure elements were found for the backbone conformation of the endocyclic residues Tyr2-Asn5. For this portion of the peptide sequence, various conformational equilibria were detected which matched different time scales. For [Arg8]vasopressin, averaged NMR parameters were obtained which could be explained by rapid interconversion between different beta-turn geometries, whereas multiple slowly exchanging conformations were observed for the V1 antagonists. V1 antagonists containing sarcosine in position 7 exhibited multiple spectral patterns for the exocyclic part attributed to cis/trans isomerization. The X-ray structure of deamino-oxytocin [Wood, S. P., Tickle, I. J., Treharne, A. M., Pitts, J. E., Mascarenhas, Y., Li, J. Y., Husain, J., Cooper, S., Blundell, T. L., Hruby, V. J., Buku, A., Fischman, A. J. & Wyssbrod, H. R. (1986) Science 232, 633-636] was found to represent one sample of the conformational space covered by the multiple conformations found for [Mca1, Arg8]vasopressin. PMID- 1935935 TI - Pig kidney 3,4-dihydroxyphenylalanine (dopa) decarboxylase. Primary structure and relationships to other amino acid decarboxylases. AB - The complete amino acid sequence of pig kidney 3,4-dihydroxyphenylalanine (Dopa) decarboxylase is reported. The sequence was determined from analysis of peptides isolated after tryptic and cyanogen bromide cleavages of the enzyme. Each subunit is made up of 485 residues, corresponding to a molecular mass of 53858 Da. The N terminus of the polypeptide chain is an acetylated methionyl residue. A number of structural features, previously shown to be important for the structure and function of the enzyme, could be localized along the polypeptide chain. Comparison of the primary structure with the known cDNA-deduced sequences of other Dopa decarboxylases (i.e. the human, bovine, rat, guinea-pig and Drosophila enzymes) reveals 50% identity. The identity increases to 73%, if the comparison is restricted to the mammalian sequences. Comparison with other aromatic and non aromatic decarboxylases allows some consideration to be made in terms of structure/function and evolutionary relationships in this class of enzymes. PMID- 1935934 TI - Functional characterization of human recombinant apolipoprotein AIV produced in Escherichia coli. AB - Apolipoprotein AIV (apoAIV), a protein which is known to activate the enzyme lecithin: cholesterol acyltransferase, to bind to apoAI/AII receptor sites and also to promote cholesterol efflux from adipose cells, may play an important role in reverse cholesterol transport. In this report, the high-level production of soluble recombinant mature human apoAIV (isoform 1) in Escherichia coli is described. The recombinant protein was purified by avoiding lipid extraction or denaturation. The apoAIV preparation was analysed by its reactivity with antibodies raised against human apoAIV, SDS-gel electrophoresis, isoelectric focusing and N-terminal sequencing. The purified recombinant protein retains an extra methionine at the N-terminus. Purified recombinant and natural apoAIV proteins were indistinguishable with regard to their denaturation properties, thermo-stability or their fluorescence emission properties in the presence of various quantities of a quenching agent. Complexes of ApoAIV with L-alpha dimyristoyl-glycerophosphocholine (Myr2GroPCho), glycerophosphocholine (GroPCho), or L-alpha-1-palmitoyl-2-oleoylglycerophosphocholine (PamOleGroPCho) prepared from plasmatic and from recombinant apoAIV proteins have similar densities as revealed by analytical centrifugation. They also share the same cofactor properties for the lecithin:cholesterol acyltransferase reaction. Recombinant apoAIV complex with Myr2GroPCho was also able to bind to the same apoAI/AII receptor sites and to promote cholesterol efflux to an equal extent from adipose cells. It is concluded that the recombinant protein is functionally identical to the plasmatic apoAIV and may therefore be very useful in helping to elucidate the physiological role of apoAIV. PMID- 1935936 TI - Affinity labeling of pig kidney 3,4-dihydroxyphenylalanine (Dopa) decarboxylase with N-(bromoacetyl)pyridoxamine 5'-phosphate. Modification of an active-site cysteine. AB - Pig kidney 3,4-dihydroxyphenylalanine (Dopa) decarboxylase is inactivated by N (bromoacetyl)pyridoxamine 5'-phosphate (BAPMP) in a reaction which follows first order kinetics at pH 7.5 and 25 degrees C. The concentration dependence of inactivation reveals saturation kinetics with an apparent Ki of 0.16 mM and kinact of 0.086 min-1 at saturating inhibitor concentration. Enzyme can be protected from inactivation by pyridoxal 5'-phosphate. Inactivation of enzyme by [14C]BAPMP proceeds with the incorporation of a stoichiometric amount of labeled inhibitor. Proteolytic digestions of the radioactively labeled enzyme followed by high-performance liquid chromatography allow the isolation of the modified peptide corresponding to the sequence Ala-Ala-Ser-Pro-Ala-Cys-Thr-Glu-Leu in which cysteine (Cys111) is the modified residue. The conservation of this residue and also of an extended region around it in all Dopa decarboxylases so far sequenced is underlined. The overall conclusion of these findings is that Cys111 may be at, or near, the pyridoxal-5'-phosphate binding site of pig kidney Dopa decarboxylase and plays a critical role in the catalytic function of the enzyme. Furthermore, fluorescence studies of BAPMP-modified apoenzyme provide useful information on the microenvironment of the affinity label at its binding site. PMID- 1935937 TI - Effects of ions on vanadate-induced photocleavage of myosin subfragment 1. AB - Myosin subfragment 1 (S1) is cleaved by near-ultraviolet irradiation in the presence of vanadate at three sites located at 23, 31 and 74 kDa from the N terminus. Since vanadate is considered to be a good structural analogue of phosphate, it is assumed that the cleavage sites participate in forming the phosphate-binding site(s) of S1. In this work, the effect of various ions on the vanadate-induced photocleavage of S1 was studied. Monovalent anions were found to inhibit photocleavage in the 50-200 mM range. The inhibition is more expressed at a site 74 kDa from the N-terminus than at the 23-kDa and 31-kDa sites. The inhibitory effect of the monovalent anions increases in the order acetate = F- less than Cl- less than Br- less than I- = SCN-. The order of the inhibitory effect is identical to the protein-structure-damaging effect of monovalent anions in the von Hippel series [von Hipel, P. H. & Wong, K. Y. (1964) Science 145, 577 581]. Therefore, it is assumed that decreased photocleavage is due to local perturbations of structure, especially at the 74-kDa site, in addition to increased ionic strength. Divalent anions, sulfate and thiosulfate, strongly inhibit photocleavage at 2 mM. The inhibition is very pronounced at the 23-kDa and 31-kDa sites, while the 74-kDa site is hardly affected. Since photocleavage at the 23-kDa and 31-kDa sites is regulated jointly and independently from cleavage at the 74-kDa site, it is assumed that S1 has two distinct phosphate binding sites: the regions of the 23-kDa and 31-kDa cleavage sites, which are proximal to each other in the spatial structure, participate in forming the first phosphate-binding site, while the 74-kDa site is part of the second binding site. Sulfate was also found to inhibit the trapping of vanadate and to facilitate its release from the S1-MgADP-Vi (Vi, inorganic vanadate) complex. Photocleavage of S1 takes place at all three sites, both in the presence or absence of divalent cations, indicating that these, including Mg2+, are not essential for cleavage. PMID- 1935938 TI - Some properties of site-specific mutants of human carbonic anhydrase II having active-site residues characterizing carbonic anhydrase III. AB - Four amino acid residues, His64, Asn67, Leu198 and Val207, in the active site of human carbonic anhydrase II, have been replaced by Lys64, Arg67, Phe198 and Ile207, which are characteristic for the muscle-specific, low-activity isoenzyme form, carbonic anhydrase III. The aim of the investigation has been to test if any of these residues, or a combination of them, is important for the low CO2 hydration activity, low esterase activity, low pKa for the pH/rate profile and low affinity for sulfonamide inhibitors characterizing carbonic anhydrases III. However, no evidence for such critical roles was found. A combination of Lys64 and Arg67 appears to result in a decrease in CO2 hydration activity, but even the quadruple mutant having all four changes is only eight times less active (kcat/Km) than unmodified isoenzyme II, in contrast to isoenzyme III which is nearly 300 times less active than isoenzyme II. The 4-nitrophenyl acetate hydrolase activity of the quadruple mutant is sevenfold lower than that of unmodified isoenzyme II, while the active site of isoenzyme III hardly catalyzes the hydrolysis of this ester at all. The pKa controlling the esterase activity of the quadruple mutant is 6.2, which should be compared to a value of 6.8 for unmodified isoenzyme II, and about 5 for isoenzyme III. While isoenzyme III binds sulfonamide inhibitors 10(3)-10(4) times less strongly than isoenzyme II, only [Asn-67----Arg]isoenzyme II shows a weaker binding of the investigated sulfonamide, dansylamide, but only by a factor of two. Some of the other mutants show enhanced affinities, up to nearly fourfold for the double mutant with Phe198 and Ile207. It is speculated that additional differences between the active sites of isoenzyme II and III might be important for the precise orientations and interactions of the side chains of isoenzyme-III-specific amino acid residues. PMID- 1935939 TI - Neutral endopeptidase activity in the interaction of N-formyl-L-methionyl-L leucyl-L-phenylalanine with human polymorphonuclear leukocytes. AB - Human polymorphonuclear leukocytes (PMN) hydrolyze the synthetic chemoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe) at nanomolar concentrations in an autocatalytic-like manner that deviates from classical Michaelis-Menten kinetics [Yuli, I. & Snyderman, R. (1986) J. Biol. Chem. 261, 4902-4908]. By using inhibitors of distinct classes of endoproteases, this particular fMet-Leu-Phe degradation was attributed exclusively to an exoplasmic metalloendoprotease that matches the ubiquitous neutral endopeptidase (NEP). Membrane-bound NEP hydrolyzes non-chemotactic substrates according to a classic Michaelis-Menten mechanism. By competitive inhibition with non-chemotactic substrates, fMet-Leu-Phe was found to interact with membrane NEP through a single active site, in a non-cooperative mode with an apparent Km in the order of 1 mM. The discrepancy between the ordinary hydrolysis of the micromolar and millimolar concentrations of fMet-Leu-Phe, reported by others, and the particular degradation of the nanomolar fMet-Leu-Phe, could not be accounted for by any coherent correlation between NEP activity/inhibition and modulation of fMet-Leu Phe binding to its receptor, and/or induction of fMet-Leu-Phe-receptor-mediated inflammatory responses. Based on these and previously reported results, a novel model is proposed in which the fMet-Leu-Phe-induced inflammatory stimulation of PMN involves both NEP and the fMet-Leu-Phe receptor. By this model, NEP and the fMet-Leu-Phe receptor are distinct membrane entities which can form dynamic binary and tertiary complexes; thus accounting for the unusual kinetic features of fMet-Leu-Phe degradation, as well as the two receptor states. The complex of NEP and the fMet-Leu-Phe receptor might be conceived as a chemotactic-perception mechanism that combines the high affinity of the receptor and the rapid turnover of NEP. PMID- 1935940 TI - Characterisation of the DNA-polymerase-alpha-primase complex from the silk glands of Bombyx mori. AB - Silk gland cells of Bombyx mori undergo chromosomal endoduplication throughout larval development. The DNA content of both posterior and middle silk gland nuclei increased by 300,000 times the haploid genomic content, amounting to 18 rounds of replication. The DNA doubling time is approximately 48 h and 24 h during the fourth and fifth instars of larval development. However, DNA content does not change during the interim moult. Concomitant with DNA content, DNA polymerase activity also increases as development progressed. Enzyme activity is predominantly due to DNA polymerase alpha with no detectable level of polymerase beta. DNA polymerase alpha from silk gland extracts was purified to homogeneity (using a series of columns involving ion-exchange, gel-filtration and affinity chromatography), resulting in a 4000-fold increase in specific activity. The enzyme is a heterogeneous multimer of high molecular mass, and the catalytic (polymerase) activity is resident in the 180-kDa subunit. The enzyme shows a pI of 6.2 and the Km values for the dNTP vary over 5-16 microM. The polymerase is tightly associated with primase activity and initiates primer synthesis in the presence of ribonucleoside triphosphates on a single-stranded DNA template. The primase activity is resident in the 45-kDa subunit. The enzyme is devoid of any detectable exonuclease activity. The abundance of DNA polymerase alpha in silk glands and its strong association with the nuclear matrix suggest a role in the DNA endoduplication process. PMID- 1935941 TI - Characterization and 400-MHz 1H-NMR analysis of urinary fucosyl glycoasparagines in fucosidosis. AB - Fucosyl glycoasparagines accumulating in the urine of a patient with fucosidosis were isolated using reverse-phase HPLC. Structural analysis of 25 glycoasparagines was carried out by combination of methylation and 400-MHz 1H-NMR spectroscopy analyses. The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L fucosidase deficiency. All of the glycoasparagines possess a fucose residue alpha 1,6-linked to the GlcNAc 1 residue attached to asparagine. Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type. PMID- 1935942 TI - Identification of a novel UDP-Gal:GalNAc beta 1-4GlcNAc-R beta 1-3 galactosyltransferase in the connective tissue of the snail Lymnaea stagnalis. AB - Connective tissue of the freshwater pulmonate Lymnaea stagnalis was shown to contain galactosyltransferase activity capable of transferring Gal from UDP-Gal in beta 1-3 linkage to terminal GalNAc of GalNAc beta 1-4GlcNAc-R [R = beta 1 2Man alpha 1-O(CH2)8COOMe, beta 1-OMe, or alpha,beta 1-OH]. Using GalNAc beta 1 4GlcNAc beta 1-2Man alpha-1-O(CH2)8COOMe as substrate, the enzyme showed an absolute requirement for Mn2+ with an optimum Mn2+ concentration between 12.5 mM and 25 mM. The divalent cations Mg2+, Ca2+, Ba2+ and Cd2+ at 12.5 mM could not substitute for Mn2+. The galactosyltransferase activity was independent of the concentration of Triton X-100, and no activation effect was found. The enzyme was active with GalNAc beta 1-4GlcNAc beta 1-2Man alpha 1-O(CH2)8COOMe (Vmax 140 nmol.h-1.mg protein-1; Km 1.02 mM), GalNAc beta 1-4GlcNAc (Vmax 105 nmol.h-1.mg protein-1; Km 0.99 mM), and GalNAc beta 1-4GlcNAc beta 1-OMe (Vmax 108 nmol.h 1.mg protein-1; Km 1.33 mM). The products formed from GalNAc beta 1-4GlcNAc beta 1-2Man alpha 1-O(CH2)8COOMe and GalNAc beta 1-4GlcNAc beta 1-OMe were purified by high performance liquid chromatography, and identified by 500-MHz 1H-NMR spectroscopy to be Gal beta 1-3GalNAc beta 1-4GlcNAc 1-OMe, respectively. The enzyme was inactive towards GlcNAc, GalNac beta 1-3 GalNAc alpha 1-OC6H5, GalNAc alpha 1--ovine-submaxillary-mucin, lactose and N-acetyllactosamine. This novel UDP-Gal:GalNAc beta 1-4GlcNAc-R beta 1-3-galactosyltransferase is believed to be involved in the biosynthesis of the hemocyanin glycans of L. stagnalis. PMID- 1935943 TI - Post-transcriptional effect of ultraviolet light on gene expression in human cells. Stabilization of cytokine-induced and poly(I).poly(C)-induced messenger RNA. AB - It is well established that ultraviolet light modulates gene expression in mammalian cells, particularly at transcriptional and post-translational levels. The present study was undertaken to investigate whether the fate of mRNA is also altered in ultraviolet-light-irradiated human cells. In order to facilitate distinction between transcriptional and post-transcriptional effects, this analysis has focused on six genes whose transcription is conditional on the supply of exogenous inducers, interferon-alpha, interleukin-1 alpha or the double stranded RNA, poly(I).poly(C). Human cells induced to express these genes were found to retain a significantly higher concentration of corresponding transcripts when irradiated with ultraviolet light at the end of the inducing treatment. This stimulation was due to dose-dependent ultraviolet-light stabilization of preformed mRNA, as shown by run-on and pulse/chase experiments. This work uncovers a new facet of the cellular response to genotoxic stresses, i.e. extension of the life-span of transcription products. Whether this stabilizing effect contributes to cell recovery by promoting gene expression remains to be determined. PMID- 1935944 TI - Conformational studies on a peptide fragment representing the RNA-binding N terminus of a viral coat protein using circular dichroism and NMR spectroscopy. AB - Conformational studies were performed on a synthetic pentacosapeptide representing the RNA-binding N-terminal region of the coat protein of cowpea chlorotic mottle virus. The effects of ionic strength, addition of (oligo)phosphates and temperature on the conformation of this highly positively charged peptide containing six arginines and three lysines were studied. CD experiments show that the peptide has 15-18% alpha-helical conformation and about 80% random-coil conformation in the absence of inorganic salt at 25 degrees C, and 20-21% alpha-helical conformation under the same conditions at 10 degrees C. Addition of inorganic salts results in an increase of alpha-helix content, up to 42% in the presence of oligophosphate with an average chain length of 18 phosphates, which was used as an RNA analog. NMR experiments show that the alpha helix formation starts in the region between Thr9 and Gln12, and is extended in the direction of the C terminus. Relaxation measurements show that binding to oligophosphates of increasing length results in reduced internal mobilities of the positively charged side chains of the arginyl and lysyl residues and of the side chain of Thr9 in the alpha-helical region. The alpha-helix formation in the N-terminal part of this viral coat protein upon binding of phosphate groups to the positively charged side chains is suggested to play an essential role in RNA binding. PMID- 1935945 TI - Isolation and structural characterization of an insulin-related molecule, a predominant neuropeptide from Locusta migratoria. AB - Neurohaemal lobes of corpora cardiaca of Locusta migratoria are an established storage site for neurohormones produced by the neurosecretory cells of the brain. As previously reported [Hietter, H., Van Dorsselaer, A., Green, B., Denoroy, L., Hoffmann, J.A. & Luu, B. (1990) Eur. J. Biochem. 187, 241-247], the isolation and characterization of a novel 5-kDa peptide from these lobes served as the basis for oligonucleotide screening of cDNA libraries prepared from poly(A) RNA from neurosecretory cells of the central nervous system. From subsequent cDNA cloning studies [Lagueux, M., Lwoff, L., Meister, M., Goltzene, F. & Hoffmann, J.A. (1990) Eur. J. Biochem. 187, 249-254], the existence of a 145-residue precursor protein was deduced, which contained, in addition to the 5-kDa peptide, amino acid sequences with homology to the A and B chains of an insulin-related peptide. In the present study we have isolated the native molecule from corpora cardiaca of Locusta and characterized, by Edman degradation and plasma-desorption mass spectrometry, the two chains as follows: A chain, Gly-Val-Phe-Asp-Glu-Cys-Cys-Arg Lys-Ser-Cys-Ser-Ile-Ser-Glu-Leu-Gln-Thr- Tyr-Cys - Gly (Ile, isoleucine); B chain, Ser-Gly-Ala-Pro-Gln-Pro-Val-Ala-Arg-Tyr-Cys-Gly-Glu-Lys-Leu-Ser-Asn-Ala- Leu-Lys - Leu-Val-Cys-Arg-Gly-Asn-Tyr-Asn-Thr-Met-Phe. Taken in conjunction with the previous cloning studies, our data lead to a clear picture of the processing of Locusta preproinsulin. They indicate that locusta corpora cardiaca contain remarkably large amounts of one single insulin form, in contrast to multiple insulin isoforms of Bombyx mori, the only other insect species from which insulin related peptides have been isolated and characterized [Nagasawa, H., Kataoka, H., Isogai, A., Tamura, S., Suzuki, A., Mizoguchi, A., Fujiwara, Y., Suzuki, A., Takahashi, S. & Ishizaki, H. (1986) Proc. Natl Acad. Sci. USA 83, 5840-5843]. PMID- 1935946 TI - Specificity determinants for tyrosine protein kinase. A study with recombinant hirudin mutants. AB - Hirudin, the powerful anticoagulant agent of leech (Hirudo medicinalis) saliva, was readily phosphorylated by two spleen tyrosine protein kinases (TPK-IIB and TPK-III) at Tyr63 with Km values of 238 microM and 74 microM, respectively. The synthetic tridecapeptide DGDFEEIPEEYLQ, corresponding to the hirudin 53-65 C terminal fragment, was phosphorylated even more efficiently than hirudin itself. Four hirudin mutants, in which one or more of the glutamic acids at positions 57, 58, 61 and 62 have been replaced by glutamines, were poorer substrates than hirudin. The mutant in which all four glutamates were substituted, [Gln57,58,61,62]hirudin, was virtually not phosphorylated by either TPK-IIB and TPK-III. Substitution of Glu57 and Glu58 was less deleterious than substitution of the two glutamic acids adjacent to Tyr63: [Gln61,62]hirudin exhibited a 20 fold lower phosphorylation efficiency with TPK-IIB. With TPK-III, however, the Km value of [Gln61,62]hirudin was slightly lower, while the Vmax decreased sixfold. The substitution of Glu62 alone was also more detrimental with TPK-IIB than with TPK-III. The behaviour of a third spleen TPK, named lyn TPK-I and belonging to the src family, was markedly different in that it did not phosphorylate hirudin but exhibited significant activity towards [Gln57,58,61,62]hirudin. Taken together, these data confirm and extend with a protein substrate the results obtained with short model peptides which indicated the stringent substrate requirements of TPK-IIB (and of TPK-III to a lesser extent) for N-terminal acidic residues. In contrast, such residues are deleterious with lyn TPK-I. These observations also support the concept that tyrosine protein kinases recognize specificity determinants situated in the vicinity of the target residue rather than requiring higher-order structural features. PMID- 1935947 TI - Mechanism of NADPH oxidation catalyzed by horse-radish peroxidase and 2,4 diacetyl-[2H]heme-substituted horse-radish peroxidase. AB - The mechanism of NADPH oxidation catalyzed by horse-radish peroxidase (HRP) and 2,4-diacetyl-[2H]heme-substituted horse-radish peroxidase (DHRP) was studied. The roles of the different H2O2/peroxidase compounds were examined by spectral studies. The oxidized NADPH species were identified using the superoxide dismutase effect and by measuring the stoichiometry between NADPH oxidized and H2O2 used. In the presence of a mediating molecule, like scopoletin, both enzymes acted via a similar mechanism, producing only NADP degrees, which in turn reacted with O2 producing O2-. Consequently H2O2 was completely regenerated in the presence of superoxide dismutase and partially regenerated in its absence. In the absence of a mediating molecule, the H2O2 complex of both enzymes (compound I) catalysed NADPH oxidation by single-electron transfer, producing NADP degrees; compound II of these enzymes catalyzed NADPH oxidation more slowly by a direct two-electron transfer, producing NADPH+. There were difference between HRP and DHRP. HRP compound II was produced by the oxidation of 1 mol NADPH/mole compound I, while DHRP compound II was formed by the spontaneous conversion of compound I to compound II. The NADPH oxidation catalyzed by DHRP compound I did not lead to the formation of compound II. When H2O2 was produced slowly by the glucose/glucose-oxidase system, compound II was never formed and a pure O2- adduct of DHRP (compound III) accumulated. PMID- 1935948 TI - Isolation, purification and partial characterization of a 30-kDa chlorophyll-a/b binding protein from spinach. AB - A 30-kDa chlorophyll-a/b-binding protein was purified from photosystem II membrane fragments using Ca(2+)-chelating Sepharose 6B chromatography. The protein binds approximately four chlorophyll a molecules, one chlorophyll b molecule and carotenoids. Its 77-K fluorescence-emission spectrum exhibits a maximum at 680 +/- 1 nm. The protein has a high tendency to form a dimer in the presence of Ca2+.Ca2+ binding affects the low-temperature fluorescence-emission maximum, leading to a decrease in its intensity and a blue shift of 1 nm. Similar spectral changes were obtained in the presence of Mg2+, possibly indicating a common binding domain for both cations. We interpret these observations as cation induced conformational changes of the protein, which were reversible upon subsequent incubation in EDTA. Evidence is presented for the involvement of carboxyl groups in the coordination sphere of the bivalent cations. The possible structural and functional role of the protein is discussed. PMID- 1935949 TI - Determination of the cDNA sequence for the human mitochondrial 75-kDa Fe-S protein of NADH-coenzyme Q reductase. AB - A human-hepatoma cDNA lambda gt11 expression library was probed with an antibody to holoenzyme complex I (NADH-CoQ reductase) of the respiratory chain. One of the 30 antibody positive clones was purified to homogeneity, amplified by the polymerase chain reaction (PCR), subcloned and sequenced. It proved to be highly similar to the cDNA sequence for the bovine 75-kDa Fe--S protein. Using the sequence obtained from this library, both sense and antisense oligonucleotides were constructed and used to probe a human kidney cDNA library using PCR amplification with oligonucleotides that flank the polylinker region of the lambda phage. Two further cDNA clones were obtained which overlapped and covered the entire cDNA sequence of 2526 bp. The encoded protein of 727 amino acids has 21 amino acids that differ from the bovine-protein sequence. Northern blot analysis of mRNA from fibroblasts of complex-I deficient patients revealed no abnormalities. We show that this Fe--S protein has significant similarity with (a) the gamma chain of the hydrogen hydrogenase of Alcaligenes eutrophus and (b) the A chain of the formate dehydrogenase of Methanobacterium formicum. PMID- 1935950 TI - Purification and cDNA cloning of Xenopus laevis skin peptidylhydroxyglycine N-C lyase, catalyzing the second reaction of C-terminal alpha-amidation. AB - The alpha-amidation of glycine-extended peptides is a two-step reaction catalyzed by peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidylhydroxyglycine N-C lyase (PHL). PHL was purified to homogeneity from Xenopus laevis skin and its partial amino acid sequence (including the N-terminal 35 residues) was determined. It was found that the cDNA codes for a 935-residue precursor protein (AE-III protein), containing the PHM and PHL sequences at its N terminus and C terminus, respectively. The PHM sequence in AE-III protein is completely identical to that deduced from the nucleotide sequence of X. laevis AE I cDNA, which encodes only PHM, except that the AE-I protein has an extra 10 residues at its C terminus. It is suggested that AE-I and AE-III mRNA are encoded by the same gene and produced by alternative splicing. PMID- 1935951 TI - The catalytic domain of the dihydrolipoyl transacetylase component of the pyruvate dehydrogenase complex from Azotobacter vinelandii and Escherichia coli. Expression, purification, properties and preliminary X-ray analysis. AB - Partial sequences of the dihydrolipoyl transacetylase component (E2p) of the pyruvate dehydrogenase complex from Azotobacter vinelandii and Escherichia coli, containing the catalytic domain, were cloned in pUC plasmids and over-expressed in E. coli TG2. A high expression of a homogeneous protein was only detectable for E2p mutants consisting of the catalytic domain and the alanine-proline-rich sequence between a putative binding region for the peripheral components and the catalytic domain (apa-4). Most of the catalytic domain from A. vinelandii without the apa-4 sequence was degraded intracellularly, probably due to incorrect folding. Fusion proteins of six amino acids from beta-galactosidase, the apa-4 region and the catalytic domains of A. vinelandii or E. coli E2p could be highly purified. Both catalytic domains were assembled in 24-subunit structures with a molecular mass of approximately 670 kDa. The expression of catalytic domain from A. vinelandii E2p is more than twice as high as found for wild-type E2p. This can be explained by intracellular degradation of over-expressed wild-type E2p, whereas the catalytic domains are stable against proteolysis in vivo and in vitro. The interaction of the peripheral components pyruvate dehydrogenase (E1p) and dihydrolipoamide dehydrogenase (E3) with the catalytic domains was studied, using gel filtration on Superose-6 and sedimentation velocity experiments. No binding of either E1p or E3 to the catalytic domain of either organism was detectable. Crystals of the catalytic domain of A. vinelandii E2p could be grown to a maximum size of 0.6 x 0.6 x 0.4 mm. They diffract up to a resolution of 0.28 nm. PMID- 1935952 TI - NMR studies of the activation of the Escherichia coli trp repressor. AB - The Escherichia coli trp repressor binds to the trp operator in the presence of tryptophan, thereby inhibiting tryptophan biosynthesis. Tryptophan analogues lacking the alpha-amino group act as inducers of trp operon expression. We have used one- and two-dimensional 1H-NMR spectroscopy to compare the binding to the repressor of the corepressors L-tryptophan, D-tryptophan and 5-methyl-DL tryptophan with that of the inducer indole-3-propionic acid. We have determined the chemical shifts of the indole ring protons of the ligands when bound to the protein, principally by magnetization-transfer experiments. The chemical shifts of the indole NH and C4 protons differ between corepressors and inducer. At the same time, the pattern of intermolecular NOE between protons of the protein and those of the ligand also differ between the two classes of ligand. These two lines of evidence indicate that corepressors and inducers bind differently in the binding site, and the evidence suggests that the orientation of the indole ring in the binding site differs by approximately 180 degrees between the two kinds of ligand. This is in contrast to a previous solution study [Lane, A.N. (1986) Eur. J. Biochem. 157, 405-413], but consistent with recent X-ray crystallographic work [Lawson, C.L. & Sigler, P.B. (1988) Nature 333, 869-871]. D-Tryptophan and 5 methyltryptophan, which are more effective corepressors than L-tryptophan, bind similarly to L-tryptophan. The indole ring of D-tryptophan appears to bind in essentially the same orientation as that of the L isomer. There are, however, some differences in chemical shifts and NOE for 5-methyltryptophan, which indicate that there are significant differences between the two corepressors L tryptophan and 5-methyltryptophan in the orientation of the indole ring within the binding site. PMID- 1935953 TI - Identification and characterization of the lantibiotic nisin Z, a natural nisin variant. AB - Lactococcus lactis strain NIZO 22186 produces an extracellular, lanthionine containing 3.5-kDa polypeptide with antimicrobial activity. Its retention time on reversed-phase (RP) HPLC and its amino acid composition showed high similarities but no complete identity to nisin. The gene for this lantibiotic, designated nisZ, has been cloned and its nucleotide sequence was found to be identical to that of the precursor nisin gene apart from a single mutation resulting in the substitution His27Asn in the mature polypeptide. NMR studies of the natural nisin variant, which has been designated nisin Z, confirmed the His27Asn substitution and indicated that it has a similar structure to nisin. PMID- 1935954 TI - Purification and characterisation of 3-hydroxyphenylacetate 6-hydroxylase: a novel FAD-dependent monooxygenase from a Flavobacterium species. AB - 3-Hydroxyphenylacetate 6-hydroxylase was purified 70-fold from a Flavobacterium sp. grown upon phenylacetic acid as its sole carbon and energy source. The presence of FAD and dithiothreitol during purification is essential for high recovery of active enzyme. SDS/PAGE of purified enzyme reveals a single band with a minimum molecular mass of 63 kDa. Analytical gel-filtration, sedimentation equilibrium and sedimentation-velocity experiments indicate that the purified enzyme exists in solution mainly as a dimer, containing 1 molecule non-covalently bound FAD/subunit. 3-Hydroxyphenylacetate 6-hydroxylase utilizes NADH and NADPH as external electron donors with similar efficiency. The enzyme shows a narrow substrate specificity. Only the primary substrate 3-hydroxyphenylacetate is hydroxylated efficiently, yielding 2,5-dihydroxyphenylacetate as a product. During turnover, the substrate analogues 3,4-dihydroxyphenylacetate and 4 hydroxyphenylacetate are partially hydroxylated, exclusively at the 6' (2') position. The physiological product 2,5-dihydroxyphenylacetate acts as an effector, strongly stimulating NAD(P)H oxidation. The activity of 3 hydroxyphenylacetate 6-hydroxylase is severely inhibited by chloride ions, competitive to the aromatic substrate. In the native state of enzyme, two sulfhydryl groups are accessible to 5,5'-dithiobis(2-nitrobenzoate). Titration with stoichiometric amounts of either 5,5'-dithiobis(2-nitrobenzoate) or mercurial reagents completely blocks enzyme activity. Inactivation by cysteine reagents is inhibited by the substrate 3-hydroxyphenylacetate. The original activity is fully restored by treatment of the modified enzyme with dithiothreitol. The N-terminal amino acid sequence of the enzyme lacks the consensus sequence GXGXXG, found at the N-termini of all flavin-dependent external monooxygenases sequenced so far. The amino acid composition of 3 hydroxyphenylacetate 6-hydroxylase is also presented. PMID- 1935955 TI - Purification and characterisation of an archaebacterial succinate dehydrogenase complex from the plasma membrane of the thermoacidophile Sulfolobus acidocaldarius. AB - A succinate dehydrogenase complex was isolated in a three-step purification from plasma membranes of the thermoacidophilic archaebacterium Sulfolobus acidocaldarius. It consists of four subunits: a, 66 kDa; b, 31 kDa; c, 28 kDa and d, 12.8 kDa. In the 141-kDa native protein, the four subunits are present in an equimolar stoichiometry. The complex contains acid-non-extractable flavin, iron and acid-labile sulphide. Maximal succinate dehydrogenase activities were recorded at pH 6.5, which coincides with the internal pH of Sulfolobus cells. The temperature optimum of 81 degrees C defines the Sulfolobus succinate dehydrogenase as a thermophilic enzyme complex. The Km for succinate was found to be 1.42 mM (55 degrees C). Similar to the mitochondrial soluble succinate dehydrogenase, this enzyme is capable of transferring electrons to artificial electron acceptors, for instance phenazine methosulfate, N,N,N',N'-tetramethyl-p phenylenediamine and ferricyanide. In contrast to the mitochondrial succinate dehydrogenase, the archaebacterial enzyme reduces 1,4-dichloroindophenol also in the absence of phenazine methosulfate. Caldariella quinone, the physiological electron mediator in the Sulfolobus respiratory chain, was only slowly reduced under adjusted conditions. The succinate--phenazine methosulfate-(1,4 dichloroindophenol) oxidoreductase of the isolated complex was strongly inhibited by tetrachlorobenzoquinone. In plasma membranes the complex reduces molecular oxygen in a cyanide-sensitive reaction. Polyclonal Sulfolobus anti-a antibodies crossreacted with 66-67-kDa polypeptides from membranes of Thermoplasma acidophilium, Sulfolobus solfataricus and beef heart submitochondrial particles. PMID- 1935956 TI - Rapid purification and characterization of protein kinase C from bovine retinal rod outer segments. AB - A rapid FPLC procedure for the purification of protein kinase C from bovine rod outer segments is described. The enzyme is essentially homogeneous after purification and exhibits a molecular mass of approximately 85 kDa, as determined by SDS/PAGE. From its chromatographic behaviour on hydroxyapatite, and from Western-blotting experiments using isoenzyme-specific antibodies, we were able to identify the bovine rod outer segment protein kinase C as being of the alpha or type-III form. The purified protein kinase C has a specific activity of 1066 nmol 32P.min-1.mg protein-1, and shows a 30-fold activation upon the addition of the effectors Ca2+, PtdSer and 1,2-diacylglycerol. Arachidonic acid and linoleic acid were also found to enhance significantly the activity of the purified enzyme. PMID- 1935957 TI - Substrate specificity and stereoselectivity of horse liver alcohol dehydrogenase. Kinetic evaluation of binding and activation parameters controlling the catalytic cycles of unbranched, acyclic secondary alcohols and ketones as substrates of the native and active-site-specific Co(II)-substituted enzyme. AB - 1. The steady-state parameters kcat and Km and the rate constants of hydride transfer for the substrates isopropanol/acetone; (S)-2-butanol, (R)-2-butanol/2 butanone; (S)-2-pentanol, (R)-2-pentanol/2-pentanone; 3-pentanol/3-pentanone; (S) 2-octanol and (R)-2-octanol have been determined for the native Zn(II)-containing horse-liver alcohol dehydrogenase (LADH) and the specific active-site-substituted Co(II)LADH. 2. A combined evaluation of steady-state kinetic data and rate constants obtained from stopped-flow measurements, allowed the determination of all rate constants of the following ordered bi-bi mechanism: E in equilibrium E.NAD in equilibrium E.NAD.R1R2 CHOH in equilibrium E.NADH.R1R2CO in equilibrium E.NADH in equilibrium E. 3. On the basis of the different substrate specificities of LADH and yeast alcohol dehydrogenase (YADH), a procedure has been developed to evaluate the enantiomeric product composition of ketone reductions. 2-Butanone and 2-pentanone reductions revealed (S)-2-butanol (86%) and (S)-2-pentanol (95%) as the major products. 4. The observed enantioselectivity implies the existence of two productive ternary complexes; E.NADH.(pro-S) 2-butanone and E.NADH.(pro-R) 2-butanone. All rate constants describing the kinetic pathways of the system (S) 2-butanol, (R)-2-butanol/2-butanone have been determined. These data have been used to estimate the expected enantiomer product composition of 2-butanone reductions using apparent kcat/Km values for the two different ternary-complex configurations of 2-butanone. Additionally, these data have been used for computer simulations of the corresponding reaction cycles. Calculated, simulated and experimental data were found to be in good agreement. Thus, the system (S)-2 butanol, (R)-2-butanol/2-butanone is the first example of a LADH-catalyzed reaction for which the stereochemical course could be described in terms of rate constants of the underlying mechanism. 5. The effects of Co(II) substitution on the different steps of the kinetic pathway have been investigated. The free energy of activation is higher for alcohol oxidation and lower for ketone reduction when catalyzed by Co(II)LADH in comparison to Zn(II)LADH. However, the free energies of binding are affected by metal substitution in such a way that the enantioselectivity of ketone reduction is not significantly changed by the substitution of Co(II) for Zn(II). 6. Evaluation of the data shows that substrate specificity and stereoselectivity result from combination of the free energies of binding and activation, with differences in binding energies as the dominating factors. In this regard, the interactions of substrate molecules with the protein moiety are dominant over the interactions with the catalytic metal ion. PMID- 1935958 TI - Effect of retinoic acid on the synthesis of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in human endothelial cells. AB - The synthesis of plasminogen activators and inhibitors in endothelial cells is highly regulated by hormones, drugs and growth factors. The present study evaluates the effect of retinoic acid on the synthesis of tissue-type plasminogen activator (t-PA) and of plasminogen activator inhibitor-1 (PAI-1) by cultured human umbilical vein endothelial cells (HUVEC). Retinoic acid produced a time- and concentration-dependent increase in the secretion of t-PA-related antigen but not of PAI-1 related antigen into the culture medium. A maximal sevenfold increase of t-PA antigen after 24 h was observed with 10 microM and a half maximal increase with 0.1 microM retinoic acid. Retinoic acid induced a time dependent increase of the t-PA mRNA, with a maximum at 8 h and returning to normal at 24 h. The protein kinase inhibitor H7 decreased the t-PA antigen induced by both retinoic acid and phorbol 12-myristate 13-acetate. These results suggest that treatment of HUVEC with retinoic acid increases t-PA production by a pathway which, at some level, involves protein kinases. Thus, retinoic acid induces t-PA synthesis in the absence of altered PAI-1 synthesis, which may enhance the fibrinolytic potential of the endothelium. PMID- 1935959 TI - Multiple mRNA species code for two non-allelic forms of ovine alpha s2-casein. AB - The two non-allelic forms of alpha s2-casein, occurring in ovine milk, differ by an internal deletion of nine amino acid residues, including both cysteine residues at positions 34 and 42 in the mature chain. Sequencing of several alpha s2-casein cDNA, isolated from the mammary cDNA library of a single lactating ewe, showed three new types which differed from that previously studied. In addition to the expected deletion of codons +34 to +42 affecting 30-40% of mRNA, another structural difference involving an internal stretch of 44 nucleotides in the 5' untranslated region, was found. S1-nuclease protection assays confirmed the existence of several types of the relevant mRNA and sequencing of in-vitro amplified genomic DNA demonstrated the presence of the 44-nucleotide stretch in the alpha s2-casein transcriptional unit, thus ruling out the possibility of a cloning artefact. The different alpha s2-casein mRNA, four in terms of deletion and two in terms of nucleotide substitutions for a given ewe, can be readily explained by partial exon skipping and allelic differences, respectively. This assumption is well supported by the following observations: 5' and 3' ends of both deleted DNA fragments are similar to those of exons; sequences neighbouring the 44-nucleotide stretch of the genomic DNA perfectly match consensus sequences described for 3' and 5' ends of introns; the rather simple patterns observed on Southern blots of different enzymatic digests of genomic DNA strongly suggest the occurrence of only 1 copy alpha s2-casein gene/haploid genome. During the course of evolution, the alpha s2-casein-encoding gene has undergone many mutations and some of them might have occurred in regions corresponding to consensus splicing regions of the pre-mRNA. Thus, complete skipping of some exons might be responsible for the shorter sizes of rat and mouse alpha s2-casein mRNA. If so, the overall organization of the alpha s2-casein gene in the different species might be more similar than expected from structural comparisons of the cognate mRNA or caseins. PMID- 1935960 TI - Mitochondrial translational-initiation and elongation factors in Saccharomyces cerevisiae. AB - C155 and E252 are respiratory-defective mutants of Saccharomyces cerevisiae, previously assigned to complementation groups G37 and G142, respectively. The following evidence suggested that both mutants were likely to have lesions in components of the mitochondrial translational machinery: C155 and E252 display a pleiotropic deficiency in cytochromes a, a3 and b; both strains are severly limited in their ability to incorporate radioactive methionine into the mitochondrial translation products and, in addition, display a tendency to loose wild-type mitochondrial DNA. This set of characteristics is commonly found in strains affected in mitochondrial protein synthesis. To identify the biochemical lesions, each mutant was transformed with a wild-type yeast genomic library and clones complemented for the respiratory defect were selected for growth on a non fermentable substrate. Analysis of the cloned genes revealed that C155 has a mutation in a protein which has high sequence similarity to bacterial elongation factor G and that E252 has a mutation in a protein homologous to bacterial initiation factor 2. Disruption of the chromosomal copy of each gene in a wild type haploid yeast induced a phenotype analogous to that of the original mutants, but does not affect cell viability. These results indicate that both gene products function exclusively in mitochondrial protein synthesis. Subcloning of the IFM1 gene, coding for the mitochondrial initiation factor, indicates that the amino-terminal 423 residues of the protein are sufficient to promote peptide chain initiation in vivo. PMID- 1935961 TI - Tricholongins BI and BII, 19-residue peptaibols from Trichoderma longibrachiatum. Solution structure from two-dimensional NMR spectroscopy. AB - Two nonadecapeptides, tricholongins BI and BII, which display antifungal and antibacterial activities, have been isolated from in vitro cultures of the fungus Trichoderma longibrachiatum. The peptides were separated by reversed-phase HPLC; their amino acid compositions were determined by gas chromatography and their sequences by positive-ion fast-atom-bombardment mass spectrometry and high-field NMR. These linear peptides, containing mainly hydrophobic L-amino acids, 8-9 2 aminoisobutyric acid residues and exhibiting an acetylated N-terminal residue and an amino alcohol C-terminal leucinol belong to the peptaibol class. The methanol solution structure of tricholongins BI and BII has been investigated using both one- and two-dimensional NMR techniques. The total 1H-NMR and 13C-NMR assignments are given. By a combination of the 3JNH,C alpha H coupling constant values, temperature coefficients of the NH and CO groups, amide hydrogen/deuterium exchange rate measurements and NOE data, a secondary structure for tricholongins in solution has been proposed. Both peptides adopt a similar alpha-helical conformation with a hinge around Pro13 resulting from two 3(10) bonds. The results suggest that the N-terminus contains mixed alpha/3(10) bonds. The membrane permeability modifications induced by tricholongins have been assayed by the use of liposomes composed of egg phosphatidylcholine with 20-30% cholesterol. The peptide-induced leakage of an entrapped fluorescent probe has been followed by fluorescence spectroscopy. In a concentration range of 0.13-0.31 microM, tricholongins induce the leakage of 50% of the entrapped material in 20 min. PMID- 1935962 TI - Purification and characterization of two highly different group II phospholipase A2 isozymes from a single viperid (Eristocophis macmahoni) venom. AB - Two phospholipase A2 isozymes have been purified from leaf-nosed viper by gel permeation chromatography followed by reverse-phase HPLC and cation-exchange FPLC. Both enzymes contain seven pairs of half-cystine, typical of group II phospholipase A2. Surprisingly large differences, affecting both N- and C terminal regions, exist between the two isozymes purified from the same snake venom. Exchanges occur at no less than 27 of 121 positions (22%), suggesting the possible existence of two genes for phospholipase A2. The residue identity with the enzymes from other Viperidae species is also low, only 44-48%, indicating extensive variations of this protein structure at large. Functionally, the present isozymes do not possess the cationic regions ascribed to myotoxicity and anti-coagulant effects of the enzyme. PMID- 1935963 TI - Assignment of the 600-MHz 1H-NMR spectrum of amicyanin from Thiobacillus versutus by two-dimensional NMR methods provides information on secondary structure. AB - The nearly complete assignment (pH 6.8; T 310 K) of the 1H-NMR spectrum of reduced amicyanin from Thiobacillus versutus is reported. Experimental evidence is presented, that the structure of the amicyanin contains two beta-sheets, a feature common to plastocyanins and azurins. The loops joining the beta-strands have also been identified. The loop F-G (Thr94-Phe98), together with the flanking residues Cys93 and Met99, comprises three of the four copper ligands and is short compared to similar loops in plastocyanin and azurin. His96 turns out to be the copper ligand that can be protonated. Amicyanin resembles plastocyanin in overall structure but differs from it on account of an N-terminal strand of 22 amino acids in front of strand A, shorter loops A-B, D-E and F-G and the absence of any alpha-helical segments. PMID- 1935964 TI - Spectroscopic characterization of true enzyme-substrate intermediates of aspartate aminotransferase trapped at subzero temperatures. AB - Absorption and circular dichroism spectra of stable enzyme-substrate intermediates of aspartate aminotransferase were recorded at subzero temperatures (down to -65 degrees C) in the cryosolvent water/methanol. The intermediates were formed either between the pyridoxal form of the enzyme and its amino acid substrates, or between the pyridoxamine form and its oxo acid substrates. Kd values determined by spectroscopic titration were very close to the Km values reported for the different substrates. The adsorption complex of the pyridoxal form was probably obtained on addition of cysteine sulfinate. This complex is characterized by an increased absorption at 430 nm together with a positive Cotton effect, as also observed in the case of the complex with the competitive inhibitor maleate indicating protonation of the internal aldimine. Addition of the substrates aspartate or glutamate to the pyridoxal form seemed to result in the direct accumulation of the external aldimine which showed a slight decrease in both the absorbance and the Cotton effect at 360 nm. Additionally, a bathochromic shift of 5 nm was observed in the case of glutamate. At 430 nm, only a minor increase in absorbance, but not in circular dichroism, was observed with aspartate, and no changes were found with glutamate and the substrate analog 2 methylaspartate, indicating a deprotonated external aldimine. Presumably, the ketimine intermediate was obtained on addition of the oxo acids 2-oxoglutarate or oxalacetate to the pyridoxamine form. The intermediate showed a slight bathochromic shift (2 nm) of the absorption band and decreased circular dichroism. On formation of the ketimine, a tyrosine residue, probably active-site Tyr225, becomes partly ionized. The finding that the external aldimine can probably be accumulated in the conversion of the pyridoxal to the pyridoxamine form with the natural substrates would confirm the proton abstraction at C alpha to be the rate-limiting step in the tautomerization, although with cysteine sulfinate, the formation of the external aldimine might contribute to the rate limitation. Accumulation of the ketimine in the reverse direction would indicate that the proton abstraction at C4' is rate-limiting in this half-reaction. The results demonstrate the feasibility of further structural investigations of true enzyme-substrate intermediates. PMID- 1935966 TI - Polyclonal antibodies elicited against trans-diamminedichloroplatinum(II) modified DNA and their application in nonradioactive hybridization experiments. AB - Polyclonal antibodies that bind selectively to adducts formed with DNA by chemotherapeutically inactive trans-diamminedichloroplatinum (II) [trans [Pt(NH3)2Cl2]) were produced by immunization with calf-thymus double-helical DNA modified by trans-[Pt(NH3)2Cl2] at a ratio of bound platinum/nucleotide (rb) of 0.1. High selectivity was obtained by separation of the antibodies from the antiserum with the aid of affinity chromatography on a Sepharose column. The antibodies were competitively inhibited in an ELISA assay by 25 pM trans [Pt(NH3)2Cl2] bound to double-helical DNA and 2.5 pM trans-[Pt(NH3)2Cl2] bound to denatured DNA (rb = 0.1). The conversion of monofunctional adducts, formed on DNA at the early stage of its interaction with trans-[Pt(NH3)2Cl2], to bifunctional lesions, decreased the ability of the modified DNA to competitively inhibit these antibodies. They did not cross-react with unmodified, denatured DNA, but they reacted with diethylenetriamine-chloroplatinum(II)-chloride-modified double helical DNA and with double-helical DNA treated with cis diamminedichloroplatinum(II) for a short time (10 min). The results of this work best fit a model in which one of the major antigenic determinants of double helical DNA modified by trans-[Pt(NH3)2Cl2] is the platinum atom coordinated in a monodentate or bidentate manner with non-paired nucleotide residues or perhaps a short segment of single-stranded DNA which occurs around the platination site. Nucleic acids modified by trans-[Pt(NH3)2Cl2] can be used as immuno-probes in hybridization experiments. PMID- 1935965 TI - 1,25-Dihydroxycholecalciferol-related Na+/D-glucose transport in brush-border membrane vesicles from embryonic chick jejunum. Modulation by triiodothyronine. AB - 1,25-Dihydroxycholecalciferol, when present at and above 10 nM in an organ culture system of embryonic chick jejunum, approximately doubled the rate of Na(+)-gradient-driven D-glucose uptake by brush-border membrane vesicles, but had no effect on Na(+)-independent D-glucose transfer. The sterol also had no effect on Na+ influx along an outside/inside Na+ gradient ([Na+]o = 100 mM; [Na+]i = 0 mM). This renders it unlikely that in embryonic intestine, calcitriol raises Na(+)-dependent D-glucose transport through changes in the electrochemical Na+ gradient. D-[U-14C]Glucose tracer exchange, measured under voltage-clamp condition at Na+/D-glucose equilibrium, revealed that addition of calcitriol to the culture medium approximately doubled the activity of the Na+/D-glucose transporter in the brush-border membrane. This was also reflected by an corresponding increase in the maximal velocity of the transfer process. Increased [3H]phlorizin binding after calcitriol treatment suggests that the steroid hormone activates Na+/D-glucose transport through increasing the number of carrier molecules in the brush-border membrane. 10 nM triiodothyronine, which by itself has no effect on Na(+)-dependent D-glucose transport, potentiated the effect of 1,25-dihydroxycholecalciferol such that in the presence of both hormones, Na+/D-glucose-carrier activity was increased fourfold above control levels. PMID- 1935967 TI - Isolation and characterization of a new variant of surfactin, the [Val7]surfactin. AB - Reinvestigation of surfactin, a previously studied peptidolipid surfactant from Bacillus subtilis, by fast-atom-bombardment mass spectrometry and 1H-NMR spectroscopy, as well as by chemical methods, revealed the presence of a closely related second constituent. This new compound, [Val7]surfactin, differs from the known surfactin by the C-terminal amino acid residue which is valine instead of leucine. PMID- 1935968 TI - Aluminum interrupts the formation of alkaline-ribonuclease-inhibitor complex from bovine brain. AB - The effect of aluminum on alkaline ribonuclease (RNase) and RNase inhibitor, purified from bovine brain, was investigated. Incubation of alkaline RNase with aluminum interrupted binding of RNase inhibitor to alkaline RNase. A stoichiometry of 1:1 for the binding of aluminum to brain alkaline RNase was estimated, whereas no aluminum was found to be bound to the RNase inhibitor. Aluminum-bound alkaline RNase, however, retained a full alkaline RNase activity. None of the enzyme-bound aluminum was dissociated by dialysis against 50 mM Hepes, pH 7.0, at 4 degrees C for 24 h. Citrate, EDTA, NaF and apotransferrin protected the alkaline RNase against aluminum binding. Aluminum did not bind to the incubated alkaline RNase-inhibitor complex, suggesting that aluminum might compete with RNase inhibitor for the binding site. However, the data from chemical modification and spectroscopic studies indicate that it is also highly possible that aluminum binding to the enzyme induces conformational changes at or near the inhibitor-binding site, which subsequently interrupt binding of RNase inhibitor to alkaline RNase. These results suggest that accumulation of aluminum in brain might affect the regulation of RNA metabolism. PMID- 1935969 TI - Lysine excretion by Corynebacterium glutamicum. 1. Identification of a specific secretion carrier system. AB - Corynebacterium glutamicum effectively excretes lysine when the internal lysine concentration is elevated. Lysine efflux was investigated using selected mutants which are not able to regulate lysine biosynthesis by feedback inhibition. Secretion of lysine is not the consequence of unspecific permeability of the plasma membrane but is mediated by a secretion carrier which is specific for lysine. Lysine export is characterized by high activation energy and follows Michaelis-Menten type kinetics with an internal Km of 20 mM and a Vmax of 12 nmol.min-1.mg dry cells-1. Excretion can proceed against a preexisting chemical gradient and against the electrical potential, which rules out a previously suggested pore model. Lysine excretion can also be observed in the wild-type strain especially under conditions of peptide uptake. Its possible physiological function may be related to regulation of internal amino acid concentrations under special growth conditions. PMID- 1935970 TI - Ca2+ ionophore A23187 and thrombin inhibit the pertussis-toxin-induced ADP ribosylation of the alpha-subunit of the inhibitory guanine-nucleotide-binding protein and other proteins in human platelets. AB - Inhibitory guanine-nucleotide-binding proteins (Gi proteins) are substrates for pertussis toxin and the decreased pertussis-toxin-dependent ADP ribosylation of Gi proteins upon prior specific hormonal stimulation of cells is thought to reflect the receptor-mediated activation of Gi proteins, leading to their subsequent dissociation into alpha i and beta/gamma subunits. In the present study, the effect of various platelet stimuli on the subsequent pertussis-toxin dependent ADP ribosylation of the alpha subunit of Gi (Gi alpha) in saponized platelets and platelet membranes were studied. Stimulation of intact platelets with the Ca(2+)-ionophore A23187 or thrombin, but not phorbol 12,13-dibutyrate, decreased the subsequent pertussis-toxin-dependent ADP ribosylation of Gi alpha in saponin-permeabilized platelets in a time-dependent and dose-dependent manner. Thrombin was more effective than A23187. Parallel measurements of Ca2+ mobilization and pertussis-toxin-dependent ADP ribosylation of Gi alpha in platelets showed that Ca2+ mobilization could only partly account for the decrease in pertussis-toxin-dependent ADP ribosylation in platelets stimulated by thrombin. When the ADP-ribosylation reaction was carried out in platelet membranes, a decrease in ADP ribosylation was still observed after stimulation of platelets with thrombin, but not with A23187. In addition to Gi alpha, two other proteins were found to be ADP ribosylated by pertussis toxin; their ADP ribosylation was also decreased after A23187 and thrombin stimulation of platelets. The results indicate that Ca2+ mobilization can decrease the pertussis toxin-dependent ADP ribosylation of Gi alpha in saponized platelets; the decrease of pertussis-toxin-dependent ADP ribosylation of Gi alpha after thrombin stimulation of platelets can only, in part, be explained by Ca2+ mobilization and involves additional mechanisms; the decrease in pertussis-toxin-dependent ADP ribosylation after A23187 and thrombin stimulation is not confined to G1 alpha and involves other proteins. We conclude that the decrease in pertussis-toxin dependent ADP ribosylation of Gi in thrombin-stimulated platelets might not be solely caused by a specific structural change, such as dissociation of Gi. It is likely that A23187 and thrombin stimulation of platelets generates substances which interfere with the ADP-ribosylating activity of pertussis toxin. PMID- 1935971 TI - Interferon-gamma/lipopolysaccharide-treated mouse embryonic fibroblasts are killed by a glycolysis/L-arginine-dependent process accompanied by depression of mitochondrial respiration. AB - Normal mouse embryo fibroblasts (MEF) are killed by treatment with low doses of interferon gamma (IFN-gamma) in combination with lipopolysaccharide (LPS). This cytotoxicity has previously been shown to represent an active suicidal reaction. Here we show that the time period between first contact with IFN-gamma/LPS (t = 0 h) and cell death (t = 48 h) can be separated into two distinct periods, during which glycolytic metabolism of glucose either has a positive (8-24 h) or a negative (30-48 h) effect on cytotoxicity. During the first period (8-24 h), withdrawal of glucose from the culture medium, or inclusion in the medium of the glycolytic inhibitors deoxy-D-glucose, NaF or iodoacetate, prevented later cell death. During the second period (30-48 h), withdrawal of glucose or supplementation of the culture medium with glycolytic inhibitors was no longer protective; instead it was a requirement for cell suicide to occur. Glycolytic activity during the first period was found to be increased twofold in LPS-treated MEF and almost threefold in IFN-gamma/LPS-treated MEF. A variety of agents were found both to protect cells against IFN-gamma/LPS-induced cytotoxicity and to inhibit increased glycolysis in these cells: glucocorticoids, the serine-type protease inhibitor N-acetyl-DL-phenylalanine-beta-naphthyl ester, the ADP ribosylation inhibitors 3-aminobenzamide and nicotinamide, and the transcription and translation inhibitors actinomycin and cycloheximide. Mitochondrial function, although normal in LPS-treated cells, was markedly depressed in IFN-gamma/LPS treated MEF. Specifically, malate- and succinate-driven respiration was found to be impaired. Furthermore, IFN-gamma/LPS-treated MEF contained one-third of the ATP level of LPS-treated MEF. Withdrawal of L-arginine from the culture medium prevented cell death in IFN-gamma/LPS-treated MEF. N-Methyl-L-arginine, which is an inhibitor of nitric oxide (NO.) biosynthesis from L-arginine, also inhibited cell death. In conclusion, we propose that cell death in our experiments is due to an L-arginine/glycolysis-dependent impairment of mitochondrial respiration. PMID- 1935972 TI - Expression of rat heme oxygenase in Escherichia coli as a catalytically active, full-length form that binds to bacterial membranes. AB - A plasmid, pKK-RHO, was constructed by incorporating the coding sequence of a cDNA for rat heme oxygenase into the expression vector pKK233-2. Escherichia coli strain XL1-blue transformed with pKK-RHO produced a catalytically active, full length heme oxygenase. The 32-kDa native enzyme expressed, was localized in the bacterial membranes, possibly due to the spontaneous membrane-binding properties of a hydrophobic segment in its C-terminal region. During cultivation, a few degraded forms of heme oxygenase that had lost their membrane-associative properties appeared. Probably, some bacterial proteases cut the native heme oxygenase at sites near its C-terminus and so release hydrophilic peptides of heme oxygenase from the membranes. A 30-kDa polypeptide, one of the degraded forms of heme oxygenase, retained ability to accept electrons from NADPH- cytochrome P450 reductase and also activity for catalyzing breakdown of heme to biliverdin. The cultured cells were pale green. From them we extracted green pigment(s), of which the absorption spectrum closely resembled that of biliverdin, suggesting that a large amount of the endogenous heme of E. coli was actually degraded to biliverdin by the expressed heme oxygenase. PMID- 1935973 TI - Localization of a major nidogen-binding site to domain III of laminin B2 chain. AB - The large pepsin fragments P1 and P1X, which comprise most of the rod-like domains III of the three short arms of laminin from the mouse Engelbreth-Holm Swarm tumor, possess full binding activity for nidogen in radioligand assays. Partial reduction (70-80%) of disulfide bonds in P1 did not reduce binding activity and allowed the separation of domain III segments originating from the A, B1 and B2 chains of laminin as demonstrated by sequence analysis. Only the B2 chain segment consisting of seven cysteine-rich repeats with similarity to epidermal growth factor showed substantial nidogen-binding activity. Further degradation of this component to an active 28-kDa fragment was achieved by a second pepsin digestion of partially reduced P1. This indicates that a major binding structure for nidogen is located within three or four cysteine-rich repeats occupying sequence positions 755 to about 920 in the B2 chain. The data also show that fragments P1 and P1X differ by the absence or presence of a large portion, domain IIIb, of the laminin A chain but are indistinguishable in nidogen binding. PMID- 1935974 TI - Complete amino acid sequence of endo-beta-N-acetylglucosaminidase from Flavobacterium sp. AB - The complete amino acid sequence of endo-beta-N-acetylglucosaminidase from Flavobacterium sp. has been determined by analysis of peptides after cleavage with lysyl endopeptidase, pepsin and chymotrypsin. The protein consists of a single polypeptide chain consisting of 267 amino acid residues and a molecular mass of 27972 Da. The sequence of Flavobacterium endo-beta-N acetylglucosaminidase is very close to that of the Streptomyces enzyme (endo-H), having 60% similarity and very similar hydropathy profiles. Similarities were also found between Flavobacterium endo-beta-N-acetylglucosaminidase and chitinases from Bacillus circulans, Serratia marcescens and Phaseolus vulgaris. PMID- 1935975 TI - The kinetic mechanism of the reactions catalyzed by the glutamate synthase from Azospirillum brasilense. AB - The reactions catalyzed by glutamate synthase from Azospirillum brasilense have been investigated by a combination of absorption spectroscopy, steady-state kinetic measurements and experiments with stereospecifically labelled substrate. The data show that both L-glutamine-dependent and ammonia-dependent reactions of the glutamate synthase from A. brasilense follow an identical two-site uni-uni bi bi kinetic mechanism, in which the enzyme is alternately reduced by NADPH and oxidized by the iminoglutarate formed on addition of ammonia to the C2 of 2 oxoglutarate. The spectroscopic experiments support the involvement of the enzyme chromophores (flavins and iron-sulfur centers) in both reactions. Finally, using stereospecifically labelled NADPH, we showed that the enzyme from Azospirillum is specific for the transfer of the 4S hydrogen of NADPH. During the catalysis of both L-glutamine-dependent and ammonia-dependent reactions, this hydrogen atom equilibrates with the solvent. The data obtained with glutamate synthase from A. brasilense, a diazotroph, differ significantly from those regarding the ammonia dependent reaction of other glutamate synthases. The ammonia-dependent activity of glutamate synthase from Azospirillum is not physiologically significant, representing only a segment of the overall physiological L-glutamine-dependent activity and requiring the enzyme flavins and iron-sulfur centers. Finally, the data are not consistent with the hypothesis [Geary, L. E. & Meister, A. (1977) J. Biol. Chem. 252, 3501-3508] that the small subunit of glutamate synthase is endowed with a glutamate-dehydrogenase-like activity. PMID- 1935976 TI - Specificity of glucose transport in Trypanosoma brucei. Effective inhibition by phloretin and cytochalasin B. AB - Glucose transport in the bloodstream form of the protozoan parasite Trypanosoma brucei was characterized by enzymatically measuring the D-glucose uptake. Uptake kinetics showed a concentration-dependent saturable process, typical for a carrier-mediated transport system, with an apparent Km = 0.49 +/- 0.14 mM and Vmax = 252 +/- 43 nmol.min-1.mg cell protein-1 (equal to 2.25 x 10(8) trypanosomes). The specificity of glucose transport was investigated by inhibitor studies. Glucose uptake was shown to be sodium independent; neither the Na+/K(+) ATPase inhibitor ouabain (1 mM) nor the ionophor monensin (1 microM) inhibited uptake. Transport was also unaffected by the H(+)-ATPase inhibitor N,N' dicyclohexylcarbodiimide (DCCD; 20 microM) and the uncoupler carbonylcyanide-4 (trifluoromethoxy)phenylhydrazone (FCCP; 1 microM). However, highly significant inhibition was obtained with both phloretin (82% at 0.13 mM; Ki = 64 microM) and cytochalasin B (77% at 0.3 mM; Ki = 0.44 mM), and partial inhibition with phlorizin (14% at 0.5 mM; Ki = 3.0 mM). In each case, inhibition was noncompetitive, partially reversible (45%) for phloretin and completely reversible for cytochalasin B and phlorizin. Measurement of the temperature dependent glucose uptake between 25 degrees C and 37 degrees C resulted in a temperature quotient of Q10 = 1.97 +/- 0.02 and an activation energy of Ea = 52.12 +/- 1.00 kJ/mol for glucose uptake. We conclude that glucose uptake in T. brucei bloodstream forms occurs via a facilitated diffusion system, clearly distinguished from the human erythrocyte-type glucose transporter with about a 10 fold higher affinity for glucose and about a 1000-fold decreased sensitivity to the inhibitor cytochalasin B. PMID- 1935978 TI - Complete sequence and model for the C1 subunit of the carotenoprotein, crustacyanin, and model for the dimer, beta-crustacyanin, formed from the C1 and A2 subunits with astaxanthin. AB - The complete sequence has been determined for the C1 subunit of crustacyanin, an astaxanthin-binding protein from the carapace of the lobster Homarus gammarus (L.). The polypeptide, 181 residues long, is similar (38% identity) to the other main subunit, A2 and to plasma retinol-binding protein. The tertiary structure of the C1 subunit has been modelled on that derived for the A2 subunit from the coordinates of retinol-binding protein. Residues lining the putative binding cavities and at the putative carotenoid binding sites of the two subunits are highly conserved. The carotenoid environments are characterized by a preponderance of aromatic and polar residues and the absence of charged side chains. A tentative model for the dimer, beta-crustacyanin, formed between the two subunits with their associated carotenoid ligands, is discussed. The model is based on the crystal structure of the dimer of bilin-binding protein, a member of the same superfamily. This structure has enabled us to examine mechanisms for the bathochromic spectral shift of the protein-bound carotenoid and to identify likely contact regions between dimers in octameric alpha-crustacyanin. PMID- 1935977 TI - Development-dependent expression of isozymogens of monkey pepsinogens and structural differences between them. AB - The developmental changes in the expression of monkey pepsinogens and structural differences between the polypeptides were investigated. Monkey pepsinogens included five different components, namely, pepsinogens A-(1-4) and progastricsin. Their respective relative levels and specific activities changed significantly during development. The sequential expression of genes for type-A pepsinogens was particularly noteworthy. Pepsinogen A-3 was the major zymogen at the newborn stage, accounting for nearly half of the total pepsinogens at this stage. Pepsinogen A-2 became predominant at the 4-month stage, and pepsinogen A-1 predominated at the juvenile and adult stages. Enzymatic properties of pepsinogens A-1, A-2 and A-3 were similar but not identical to those of pepsinogen A-4 and progastricsin, in particular with respect to the activation processes. Each pepsin digested various protein substrates but some differences in specificity were evident. cDNA clones for five pepsinogens were isolated, and the nucleotide sequences were determined. Each cDNA contained leader, pro, and pepsin regions that encoded 15, 47, and 326 amino acid residues, respectively, with the exception of the cDNA for progastricsin in which the pro and pepsin regions encoded 43 and 329 amino acid residues, respectively. Type-A pepsinogens exhibited a high degree of similarity, with over 96% of bases in the nucleotide sequences of the protein-coding regions being identical. Northern analysis revealed that the level of expression of genes for type-A pepsinogens and for progastricsin was significant at the fetal stage and increased with development. PMID- 1935979 TI - Limited proteolysis of tetanus toxin. Relation to activity and identification of cleavage sites. AB - Tetanus toxin is synthesized by Clostridium tetani as a 151-kDa peptide chain. The primary gene product is processed post-translationally by removal of the initiating methionine residue, formation of disulfide bridges and limited proteolysis by bacterial or exogenous proteinases. The mature toxins consist of a 52-kDa light chain and a 98-kDa heavy chain, linked together by a disulfide bond. Proteolytic nicking is accompanied by increased pharmacological potency. To identify the structural alterations involved, single-chain toxin has been subjected to limited proteolysis with various enzymes. The new N-termini have been determined by Edman degradation and the C-termini by isolation of short C terminal peptide fragments and subsequent analysis of the sequence and composition. All two-chain toxins result from proteolytic nicking within the 17 residue segment of residues 445-461. Thus, the protease(s) of the culture broth cleave on the C-terminal side of Glu449 and partially Ala456, giving rise to two heavy chain N-termini. Trypsin and clostripain first attack the C-terminal of Arg454 and later Arg448, whereas endoproteinase Arg-C cleaves the former bond only. Chymotrypsin and endoproteinase Glu-C each split a single peptide bond, i.e. that located after Tyr452 and Glu449, respectively. Papain gives rise to a large number of cleavages within the 17-residue segment, the new C-terminus being Thr445 or Asn446 and the new N-terminus being Asp460 or Leu461. Further papain digestion leads to an additional cleavage within the heavy chain between Ser863 and Lys864. The original N-terminal Pro1 and C-terminal Asp1314, predicted from the nucleotide sequence, are conserved in all proteolytic digests. The pharmacological activity of the various two-chain toxins was 5-11 times that of the single-chain toxin, as estimated from the inhibition of [3H]noradrenaline release from rat-brain homogenate. The present data on the processing and activation by limited proteolysis prove the existence of several active tetanus isotoxins. These data, together with our previous data on the localization of disulfide bridges and sulfhydryl groups (Krieglstein, K., Henschen, A., Weller, U. & Habermann, E. (1990) Eur. J. Biochem. 188, 39-45), provide the detailed protein chemical characterization of the tetanus isotoxins. PMID- 1935980 TI - The solution structures of Escherichia coli trp repressor and trp aporepressor at an intermediate resolution. AB - We have determined the solution structures and examined the dynamics of the Escherichia coli trp repressor (a 25-kDa dimer), with and without the co repressor L-tryptophan, from NMR data. This is the largest protein structure thus far determined by NMR. To obtain a set of data sufficient for a structure determination it was essential to resort to isotopic spectral editing. Line broadening observed in this molecular mass range precludes for the most part the measurement of coupling constants and stereospecific assignments, with the inevitable result that the attainable resolution of the final structure will be somewhat lower than the resolution reported for smaller proteins and peptides. Nevertheless the general topology of the protein can be deduced from the subsets of NOEs defining the secondary and tertiary structure, providing a basis for further refinement using the full set of NOEs and energy minimization. We report here (a) an intermediate resolution structure that can be deduced from NMR data, covalent, angular and van-der-Waals constraints only, without resort to detailed energy calculations, and (b) the limits of uncertainty within which this structure is valid. An examination of these structures combined with backbone amide exchange data shows that even at this resolution three important conclusions can be drawn: (a) the protein structure changes upon binding tryptophan; (b) the putative DNA binding region is much more flexible than the core of the molecule, with backbone amide proton exchange rates 1000 times faster than in the core; (c) the binding of tryptophan stabilizes the repressor molecule, which is reflected in both the appearance of additional NOEs, and in the slowing of backbone proton exchange rates by factors of 3-10. Sequence specific 1H-NMR assignments and the secondary structure of the holopressor (L tryptophan-bound form) have been reported previously [C. H. Arrowsmith, R. Pachter, R. B. Altman, S. B. Iyer & O. Jardetzky (1990) Biochemistry 29, 6332 6341]. Those for the trp aporepressor (L-tryptophan-free form), made using the same methods and conditions as described in the cited paper, are reported here. The secondary structure of the aporepressor was calculated from sequential and medium-range NOEs and is the same as reported for the holorepressor except that helix E is shorter. The tertiary solution structures for both forms of the repressor were calculated from long-range NOE data.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1935981 TI - Characterization, stability and refolding of recombinant hirudin. AB - A recombinant variant of hirudin, the blood-clotting inhibitor of the leech Hirudo medicinalis, has been characterized employing spectroscopic and hydrodynamic techniques. Conditions have been defined for efficient reconstitution of the native, disulfide-bonded inhibitor from completely unfolded, reduced polypeptide chains. The spectral properties of the native inhibitor are consistent with previous results on the solution structure of hirudin. Extremely low circular dichroism in the far ultraviolet ([theta]Mr,220 nm = -8 +/- 1 x 10(2) deg.cm2.dmol-1) indicates a very low content of regular secondary structure. Although both tyrosine residues of the recombinant inhibitor titrate around pH 10.6, typical for solvent-exposed tyrosines, fluorescence emission and near-ultraviolet circular dichroism suggest that at least one of the tyrosines is partially shielded from solvent quench, and immobilized in an asymmetric environment. Reversible thermal unfolding of hirudin around 65 degrees C is indicated by the disappearance of its dichroic absorption in the near ultraviolet and by a fourfold increase in ellipticity at 225 nm. The transition can be approximated by a two-state model with a transition enthalpy of delta Hvan't Hoff = 159 kJ/mol and a transition entropy of 464 J.mol-1.K-1. Reduced hirudin at room temperature is largely unfolded and inactive as an inhibitor of thrombin assayed with a low-molecular-mass substrate. Refolding and reoxidation are observed at alkaline pH in the presence of a mixture of glutathione and glutathione disulfide. Spectroscopy, thrombin inhibition, and reversed-phase HPLC indicate reconstitution yields close to 100% and that the reconstituted inhibitor is identical to the native starting material. PMID- 1935982 TI - Purification and biochemical characterization of dog gastric lipase. AB - A lipase was found to be present in dog stomach which appeared to be more abundant in the fundic than in the pyloric mucosa. Dog gastric lipase was extracted by soaking the gastric tissue and further purified after cation exchange, anion exchange and gel-filtration using fast protein liquid chromatography. The amino-acid composition, N-terminal amino-acid sequence, substrate specificity, interfacial and kinetic behavior and inactivation by sulfhydryl reagents were determined and compared with those of human and rabbit gastric lipases. We report for the first time that a gastric lipase is 13 times more active on long-chain than on short-chain triacylglycerols at pH 4.0, reaching a maximal specific activity of 950 U/mg on Intralipide emulsion. PMID- 1935983 TI - Purification and characterization of a monomeric isocitrate dehydrogenase with dual coenzyme specificity from the photosynthetic bacterium Rhodomicrobium vannielii. AB - An isocitrate dehydrogenase able to function with either NADP or NAD as coenzyme was purified to homogeneity from cell-free extracts of the purple photosynthetic eubacterium Rhodomicrobium vannielii using a rapid two-step procedure involving dye-ligand affinity chromatography. The enzyme was obtained in 60% yield with specific activities of 23 U.mg protein-1 (NADP-linked reaction) and 18.5 U.mg protein-1 (NAD-linked reaction). The purified enzyme was monomeric and migrated with an approximate Mr of 75,000-80,000 on both SDS/PAGE and non-denaturing PAGE. Affinity constants (Km values) of 2.5 microM for NADP and 0.77 mM for NAD and values for kcat/Km of 981,200 min-1.mM-1 (NADP) and 2455 min-1.mM-1 (NAD) indicated a greater specificity for NADP compared to NAD. A number of metabolites were examined for possible differential regulatory effects on the NADP- and NAD linked reactions, using a dual-wavelength assay. Oxaloacetate was found to be an effective inhibitor of both reactions and the enzyme was also sensitive to concerted inhibition by glyoxylate and oxaloacetate. The amino-acid composition and the identity of 39 residues at the N-terminus were determined and compared to other isocitrate dehydrogenases. The results suggested a relationship between the Rm. vannielii enzyme and the monomeric isocitrate dehydrogenase isoenzyme II from Vibrio ABE-1. PMID- 1935984 TI - In vitro reconstitution of recombinant lamin A and a lamin A mutant lacking the carboxy-terminal tail. AB - Xenopus lamin A and a lamin A mutant lacking the complete 280 amino acid long carboxy-terminal tail were expressed in bacteria and purified from inclusion bodies. Electron microscopic analysis of lamin A dimers revealed that the carboxy terminal 280 amino acids correspond to the globular domain seen in rotary shadowed wild-type lamin and that the rodlike domain consists of the short non helical amino terminus and the alpha-helical region. During reconstitution lamin A dimers first formed polar head to tail aggregates which then associated laterally resulting in paracrystals with periodic repeats of 25 nm. In the mutant, the longitudinal and lateral association of dimers had not been influenced, however, periodic repeats were absent in the filament bundles formed. Thus our data clearly demonstrate that carboxy-terminal tails are localized in light-stained regions of negatively stained paracrystals and that they are responsible for the alternating light dark staining of paracrystals. Fibrils, 2 to 3 nm thick, were a common structural element of paracrystals and filament bundles. PMID- 1935986 TI - The proteoglycan decorin is synthesized and secreted by differentiated myotubes. AB - Proteoglycans (PGs) are important components of the skeletal muscle extracellular matrix (ECM). Skeletal muscles are composed of muscle fibers and mononucleated cells. The latter are known to synthesize and secrete several PGs. Rat skeletal muscle ECM contains a chondrotin/dermatan sulfate PG which was immunoprecipitated by antibodies against rat decorin. The synthesis and secretion of PGs by a mouse cell line was analyzed during in vitro differentiation. PGs were characterized by biochemical and immunological techniques including immunocytolocalization experiments. At least three different PGs are synthesized and secreted by differentiated myotubes: a 220 to 460 kDa heparan sulfate, a 250 to 310 kDa chondroitin/dermatan sulfate, and a 75 to 130 kDa chondroitin/dermatan sulfate. This latter PG was specifically immunoprecipitated with antibodies against rat fibroblast decorin. Indirect immunocytolocalization analysis revealed that decorin was localized inside the cells, with a strong reaction around the nuclei. During differentiation the relative proportions of some PGs changed. Thus, a decrease in the relative proportion of the heparan sulfate PG was observed, whereas a significant increase in the relative proportion of decorin was detected. No change in the large chondroitin/dermatan PG was seen during the differentiation process. The possible cell sources of decorin found in rat skeletal muscle ECM are discussed. PMID- 1935987 TI - Cytology of Lepidoptera. V. The microtubule cytoskeleton in eupyrene spermatocytes of Ephestia kuehniella (Pyralidae), Inachis io (Nymphalidae), and Orgyia antiqua (Lymantriidae). AB - The structural transformations of the microtubule cytoskeleton during eupyrene meiosis were characterized in the Mediterranean mealmoth, Ephestia kuehniella. Anti-tubulin immunofluorescence was used in two strains, L and Sbr, of this species. In addition, living primary eupyrene spermatocytes from strain L were observed with phase-contrast light microscopy, and metaphase I spermatocytes were studied with the electron microscope. The analysis did not reveal strain-specific differences in the behavior of the chromatin and the microtubule cytoskeleton in eupyrene meiosis. The general pattern of the two subsequent meiotic divisions in Ephestia kuehniella did not deviate from that observed during nuclear division in other species. A bipolar spindle developed during prophase, chromatin migrated towards the poles in anaphase, and spindle elongation occurred in telophase. Spindle development and behavior were qualitatively almost identical in primary and secondary spermatocytes. The assembly of the second meiotic spindle was initiated during the depolymerization of interzone microtubules of the first division. The relationship between spindle microtubules and centrosomes, however, showed some particularities in the moth. While microtubules radiated out from the spindle poles in late prophase, most microtubules ended about half-way between the equatorial plane and the spindle poles from late prometaphase to early anaphase. The termination of most microtubules distant from the poles was confirmed using electron microscopy in Ephestia kuehniella and using anti-tubulin immunofluorescence in two other Lepidoptera species, Inachis io and Orgyia antiqua. The microtubules were oriented parallel to the pole-to-pole axis of the spindle and were confined to an area laterally sheath by membrane layers. The spindle portions between the pole-proximal termini of the microtubules and the spindle poles contained irregularly shaped membrane elements. In late anaphase, microtubules reform between the migrating chromatin plates and the spindle poles. Concomitantly with the migration of the chromosomes towards the spindle poles, interzone microtubules are assembled. The origin of most of them appears to be at the pole-distal face of the chromatin masses. PMID- 1935985 TI - Complete amino acid sequence of the epidermal desmoglein precursor polypeptide and identification of a second type of desmoglein gene. AB - The amino acid sequence of the precursor to desmoglein, a major desmosomal cadherin, has been determined from a cDNA clone from bovine muzzle epithelium, and the transcription start site, i.e., the beginning of the approximately 7.6 kb mRNA, identified by primer extension analysis. The precursor segment of 49 amino acids starts with a relatively hydrophobic stretch of 17 amino acids, conforming to the typical features of signal peptides, displays no sequence homology to the corresponding portion of other cadherins. The isolation of the complete cDNA has allowed the cloning of a desmoglein cDNA construct, which under the control of the human beta-actin promoter, was successfully used in cell transfection. In addition, a major N-glycosylation site has been identified by lectin affinity chromatography and amino acid sequencing at amino acid position 61, i.e., in the middle of the first extracellular domain. In the course of these studies we have identified, in colon carcinoma and other simple epithelial cells, another kind of desmoglein which by partial cDNA-derived sequence and by Southern blotting is clearly the product of a different gene. This suggests that there are multiple desmogleins which can be differentially expressed in various epithelia. PMID- 1935988 TI - Cytology of lepidoptera. VI. Immunolocalization of microtubules in detergent extracted apyrene spermatocytes of Ephestia kuehniella Z. AB - Apyrene meiosis was studied in two wild-type strains, L and Sbr, of the Mediterranean mealmoth, Ephestia kuehniella, using anti-tubulin immunofluorescence. The observations were supplemented by phase-contrast light microscopy of living spermatocytes from strain L. The study revealed that nuclear envelope breakdown, centrosome separation, migration of chromatin elements towards the poles, and spindle elongation also occur in apyrene spermatocytes. However, a conventional metaphase plate is never formed, and chromatin segregation is irregular and delayed. Chromosome laggards are frequent. As a rule, apyrene spindles have a low microtubule content. The two strains, L and Sbr, differ regarding the chromatin behavior during meiosis. In strain L, the developing spindles contain numerous small chromatin clumps which segregate asynchronously. The resulting daughter cells possess about the same amount of chromatin. In contrast, large chromatin clumps exist in strain Sbr at the onset of spindle formation. The chromatin blocks transiently occupy an equatorial position and elongate subsequently parallel to the spindle axis. These elongated chromatin bodies often divide highly unequally. As a consequence, secondary spermatocytes in strain Sbr differ greatly in chromatin content. Subjective assessment shows that the size of the microtubular cytoskeleton is positively correlated with the chromatin content of the cell. Hence, it is hypothesized that the chromatin content determines spindle size. This possibly comes about the number of available kinetochores which are exposed and able to stabilize microtubules of centrosomal origin attached with the kinetochores. However, a direct bearing of chromatin on spindle size is similarly conceivable. Other Lepidoptera species examined so far are compatible with a 'type L' or a 'type Sbr' pattern of apyrene meiosis. PMID- 1935989 TI - Ultrastructural localization of microtubule-associated proteins (MAP) 1 in cilia of the respiratory tract. AB - The presence and localization of high molecular weight microtubule-associated proteins of the MAP 1 class in ciliated cells of porcine and rat respiratory tract was studied by immunoblotting and immunoelectron microscopy. Ciliary shafts of the porcine tracheal epithelium were isolated using a method that minimizes contamination of the preparation by other cellular fragments and fat. Immunoblotting with rabbit antibodies to bulk MAP 1 from hog brain clearly revealed the presence of anti-MAP 1-immunoreactive high molecular weight proteins of the MAP 1 size in these preparations. To localize MAP 1 proteins at the ultrastructural level, rat and porcine tracheal epithelia were embedded in LR White and subjected to immunogold electron microscopy. Anti-MAP 1-immunoreactive material was found at ciliary shafts and basal bodies, but not at basal feet or ciliary rootlets. Interestingly, the necklace region between the shaft and the basal body of the cilium was hardly reactive with anti-MAP 1 antibodies. This may indicate a reduced stability of ciliary microtubules in this region and could be an explanation why ciliary shafts in general break more easily there than elsewhere. PMID- 1935990 TI - Multipolar mitosis in procaine-treated polyspermic sea urchin eggs and in eggs fertilized with UV-irradiated spermatozoa with a computer model to simulate the positioning of centrosomes. AB - Procaine-treated eggs can be penetrated by more than one spermatozoon. Supernumerary male pronuclei can fuse with the female one giving raise to multipolar spindles or remain isolated within the egg's cytoplasm forming their own spindle. In all types of multiple mitotic figures (asters and spindles) the distribution of asters is equidistant either uniplanar or at maximum distance like at the apices of a polyhedron. Astral rays are not different from spindle fibers: they can attach to and attract chromosomes of "foreign" mitotic figures. When several mitotic figures are present in one egg, the partner asters are always of the same size, and microtubules of one aster never interdigitate with those of others. The hypothesis that positioning of centrosomes is brought about by spreading of a centrosome organizer in the form of an expanding calotte on the surface of the nucleus (Mazia, D., Int. Rev. Cytol. 100, 49-92 (1987)) is supported by a computer model. PMID- 1935991 TI - Visualization and measurement of calcium transients in Amoeba proteus by fura-2 fluorescence. AB - A fura-2 microspectrofluorimeter was used to visualize and measure intracellular calcium transients in normal locomoting and experimentally treated Amoeba proteus. The results show that subcellular heterogeneities of cytosolic free calcium, [Ca2+]i, correlate in time and distribution with characteristic patterns of protoplasmic streaming and ameboid movement. In detail, calcium ions have a dual effect by regulating both the contractile activities of the actomyosin cortex and the rheological properties of the cytoplasmic matrix. A high resting [Ca2+]i of 1.5 to 2.0 x 10(-7) M in the uroid region or in retracting pseudopodia is associated with the transformation of rigid ectoplasmic gel into fluid endoplasmic sol, and a low [Ca2+]i of 10(-9) to 10(-8) M in the front region or in extending pseudopodia with the re-transformation of endoplasmic sol into ectoplasmic gel. Locally increased peripheral [Ca2+]i accumulations higher than 10(-7) M are also observed at places where the actomyosin cortex is known to generate motive force by contraction, i.e., in the intermediate region of orthotactic amebas or in large pseudopodia of polytactic cells. External application of 30 mM KCl abolishes the intracellular Ca2+ gradient such that [Ca2+]i attains a uniform distribution and a maximum concentration of 2 x 10(-7) M; as a consequence, cells can show a transient loss of their locomotor activity and polarity by undergoing spherulation and total contraction. On the other hand, high external Ca2+ concentrations in the range of 100 mM stabilize the bipolar cellular organization, enhance the movement velocity and induce the propagation of Ca2+ waves repeatedly running from the uroid to the front region. The significance of external ions for signal transmission and the control of dynamic activities as well as the origin and fate of calcium participating in the observed transients are discussed. PMID- 1935992 TI - Developmental appearance of thrombospondin in neonatal mouse skeletal muscle. AB - Immunocytochemical localization of the adhesive glycoprotein thrombospondin made in comparison with other components of extracellular matrices shows its sequential appearance in the mouse muscle endomysium during postnatal development. Thrombospondin, absent at birth, in contrast to laminin, type IV collagen and fibronectin, is progressively detected during the first month of neonatal life in the whole muscle extracellular matrix. Immunoblotting of thrombospondin showed the appearance 14 days after birth of a band migrating at 180 kDa corresponding to thrombospondin. A fragment of thrombospondin at 110 kDa was already present at birth, as was also a lower molecular mass band at 70 kDa. Another band at 50 kDa also appeared during development in muscle extracts. Clonal muscle cells in culture were able to synthesize thrombospondin but only at the myotube stage, since little thrombospondin was detected at the myoblast stage. These data show a development regulation of thrombospondin expression in muscle which correlates with muscle differentiation. PMID- 1935993 TI - Aortic smooth muscle cells in collagen lattice culture: effects on ultrastructure, proliferation and collagen synthesis. AB - Adult pig smooth muscle cells (SMC) were isolated from the aortic media by collagenase digestion, subcultured as monolayer, and then re-integrated into a three-dimensional network of type I collagen. The contractile state characteristic for resident arterial wall SMC changed to the synthetic, fibroblast-like state. The cells reorganized the randomly orientated collagen fibrils causing the lattice to shrink. The influence of the extracellular matrix on the ultrastructure, the proliferation, and the collagen synthesis of these SMC embedded in the collagen lattice was investigated and compared to cells cultured in monolayer. The amount of total protein and collagens synthesized by SMC embedded in lattices was lowered as compared to monolayer cultures. Whereas total protein synthesis decreased continuously during the culture period, the proportion of collagen synthesis remained at a constant level. Although cells proliferated in lattices, proliferation was clearly slowed down as compared to monolayer cultures. The ultrastructure of entrapped synthetic state SMC was comparable to that of monolayer-cultured cells. Their cytoplasm was largely filled by elements of the endoplasmic reticulum, Golgi complexes and abundant mitochondria. With prolonged culture time, electron-dense granules as well as bodies containing whorled membranes could be found in the cytoplasm. These results indicate that synthetic state SMC can exhibit differential biosynthetic activity dependent on the actual matrix environment; cells seem to be able to sense the macromolecular composition of the extracellular matrix and to modify their production of matrix components accordingly. PMID- 1935994 TI - Metabolism of cholesterol and phospholipids in cultured human vascular smooth muscle cells: differences between artery and vein-derived cells and the effect of oxygen partial pressure. AB - Human smooth muscle (SM) cells derived from vena saphena magna, aorta abdominalis and arteria mamaria were grown in culture under 40 or 145 mmHg oxygen partial pressure (pO2) and their lipid metabolism studied. Esterification of the cellular [3H]cholesterol was higher by 2.5-fold in artery derived than in vein-derived cells and was slightly higher in cultures exposed to 145 mmHg than to 40 mmHg pO2. Cholesterol efflux in the presence of high density lipoprotein (HDL) in the incubation medium was higher in artery-derived than vein-derived cells. Apolipoprotein (apo) AI also supported cholesterol efflux to a higher extent in artery than in vein-derived cells. Cholesterol efflux in the presence of apo AI was accompanied by a decrease of 50% in cellular [3H]cholesteryl ester in both cell types. SM cultures exposed to [3H]choline incorporated about 90% of the radioactivity to phosphatidylcholine (PC) and 10% to sphingomyelin (SPM). During 5 days exposure to [3H]choline, 10 to 15% and 20 to 30% of the newly synthesized PC and SPM, respectively, were released by vein-derived cells into the incubation medium. The relative amount of SPM of the total radioactive phospholipids released by vein-derived cultures was significantly higher in cultures growing under 40 mmHg than 145 mmHg pO2 reaching a value of up to 33% of the radioactive phospholipids in the incubation medium. HDL was shown to serve as an acceptor for phospholipids released by both vein and artery-derived SM cells, while free apo AI supported phospholipid efflux in artery but not in vein-derived SM cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1935995 TI - Isolation and partial characterization of the photoreceptive organelle for phototaxis of a flagellate green alga. AB - We report on the isolation and purification of structurally intact eyespot apparatuses from the naked, biflagellate green alga Spermatozopsis similis. Two eyespot-enriched fractions, separated by sucrose gradient centrifugation, retained the typical reflective properties of eyespots in situ as demonstrated by reflection confocal laser scanning microscopy. Ultrastructurally, both fractions contained eyespot plates consisting of a single layer of lipid globules. Structurally intact eyespot apparatuses, including patches of plasma membrane and chloroplast envelope overlying the eyespot plate and a single thylakoid subtending the eyespot plate, were particularly enriched in one of the two fractions (fraction 2a). Measurement of several marker enzymes and chlorophyll content (less than 0.001% of total) established the absence of most other cell organelles from the eyespot fractions. The absorption spectra of the two fractions were dominated by carotenoids with an additional shoulder at 540 nm. Following extraction with organic solvents and sodium dodecyl sulfate polyacrylamide gel electrophoresis, several proteins were found to be considerably enriched in the two fractions. In addition to several proteins in the high Mr range, at least 4 polypeptides of 35, 29, 23, and 20 kDa are selectively enriched in fraction 2a with the 29 and 20 kDa proteins being the most prominent. The presence of glycoproteins in fraction 2a was demonstrated by binding of the mannose-specific lectin Galanthus nivalis agglutinin to several high molecular weight polypeptides. In addition, a hydrophobic component with abnormal electrophoretic mobility that reacts strongly with periodic acid-Schiff and thymol/sulfuric acid was prominent in both fractions. Mass isolation and purification of the intact phototactic apparatus of a flagellate green alga now greatly facilitates the biochemical and molecular characterization of the signal transduction chain involved in green algal phototaxis. PMID- 1935996 TI - Comparison of two cytochromes P-450 from Candida maltosa: primary structures, substrate specificities and effects of their expression in Saccharomyces cerevisiae on the proliferation of the endoplasmic reticulum. AB - cDNAs were cloned, sequenced and expressed which encode two different cytochrome P-450 forms of the alkane-assimilating yeast Candida maltosa, designated as P 450Cm1 and P-450Cm2. The amino acid sequences deduced were about 55% identical. Expression in Saccharomyces cerevisiae resulted in the formation of intact microsomal P-450 systems catalyzing the hydroxylation of n-hexadecane and lauric acid with significantly different substrate preferences. A massive proliferation of the endoplasmic reticulum was observed in the S. cerevisiae cells which produced P-450. Depending on the P-450 form expressed, distinctly organized stacks of paired membranes appeared and occupied considerable areas of the cytoplasm. As shown by immunoelectron microscopy for P-450Cm1, the protein expressed was highly concentrated within these newly formed membrane structures. PMID- 1935997 TI - Accessory cell function during monocyte/macrophage differentiation: relation to interleukin-1 (IL-1 beta) production and release. AB - Human peripheral blood monocytes (Mo) can differentiate into highly active accessory cells and approach the phenotype and function of dendritic cells instead of developing into macrophages (Mph). Here we report that monocyte derived accessory cells (m-AC), but not Mph, spontaneously synthesize and release high amounts of interleukin-1 (IL-1 beta). Furthermore, m-AC retained a high T cell stimulatory activity and a non-macrophagic phenotype for at least 12 days in culture. They were shown to be weakly adherent, non-phagocytic, and most of them were negative for nonspecific esterase. In contrast, Mo differentiating into mature Mph only transiently showed an elevated accessory function but at no time appeared to release intracellular IL-1 beta into the supernatant when cultured in the absence of exogenous triggers. Additionally, they gained a high phagocytic capacity and a strong expression of Fc-receptors within 4 days. Addition of lipopolysaccharides (LPS) to Mph stimulated IL-1 beta release but concomitantly led to a strong reduction of the Mph-phenotype. Thus, the release of IL-1 beta from monocyte-derived cells negatively correlated with the expression of the Mph phenotype but did not necessarily correlate with their accessory function. These observations may reflect an antagonistic regulation of Mph phenotype and cytokine release in cells of the monocytic lineage and suggest that IL-1 beta release is not essential for accessory activity but might serve rather as an autocrine signal to prolong the accessory function of m-AC. PMID- 1935998 TI - Transmission and scanning EM-immunogold labeling of Leishmania major lipophosphoglycan in the sandfly Phlebotomus papatasi. AB - Previous studies using immunostaining and light microscopy demonstrated expression of Leishmania major lipophosphoglycan (LPG) on parasites developing in the sandfly gut from 2 days post infection. By days 4 to 7 post infection, there appeared to be large amounts of parasite-free LPG deposited on/in the microvilli and epithelial cells lining the thoracic midgut, while forward migration of parasites and the morphological changes which accompany metacyclogenesis were associated with developmental modification of the LPG molecules. Studies presented here examine this process with much greater precision using electron microscopy and immunogold labeling techniques to study the different developmental forms (nectomonads, haptomonads, paramastigotes, and metacyclics) of promastigotes in the sandfly gut. Results obtained using LPG-specific monoclonal antibodies (WIC79.3, 45D3 and the metacyclic-specific 3F12) show (1) gold labeling over the cell surface, within the flagellar pocket, and extending along the entire length of the flagellum of electron-dense nectomonads observed in the abdominal and thoracic midgut regions on days 4 and 7 post infection, and of electron-lucid haptomonads in the foregut, (2) dense labeling around the flagellar tips, by which nectomonad forms bind to the midgut microvilli, but not on the microvilli themselves or within the epithelial cells lining the midgut, (3) significant metacyclic-specific (3F12) labeling on nectomonad forms in the lumen of the midgut and attached to the microvilli, and (4) dense labeling on the cell surface of electron-lucid paramastigotes in the esophagus and in the filamentous matrix surrounding paramastigote and metacyclic forms in the esophagus and pharynx. These results are discussed in the light of the proposed roles for LPG in parasite attachment to, and survival in, the sandfly gut. PMID- 1935999 TI - Subclinical cardiotoxicity by doxorubicin: a pulsed Doppler echocardiographic study. AB - In order to detect subclinical levels of Doxorubicin (D) cardiotoxicity, 21 patients aged 42 +/- 8 years with malignancies and treated with D as a part of a multiple regimen, were evaluated. The mean cumulative dose of D was 242 +/- 112 mg.m-2 (150 to 520 mg.m-2). Patients with systemic hypertension, valvular diseases, suspected coronary artery disease, ejection fraction less than 55% as assessed by radionuclide angiography, and aged more than 50 years were excluded from the study. A Doppler echocardiographic examination was performed before and after the course of D therapy with a mean interval of 142 days. The following variables were assessed: fractional shortening (FS), ejection fraction (EF), stroke volume (SV), isovolumic relaxation time (IVRT), maximal early diastolic flow velocity (Emax), maximal late diastolic flow velocity (Amax), and mitral deceleration time (Mdt). Indices derived from 19 aged-matched normal subjects were compared to those of the patients before the course of therapy. Doppler echocardiographic measurements did not differ significantly between the control group and patients before the course of therapy. While there were no significant changes in FS, EF, and SV in the study group before and after therapy, indices of diastolic filling showed striking differences: IVRT changed from 72 +/- 11 to 87 +/- 19 ms (P less than 0.001), Emax from 81 +/- 12 to 65 +/- 17 cm.s-1 (P less than 0.001), Mdt from 174 +/- 25 to 183 +/- 34 ms (P less than 0.05), Amax from 44 +/- 17 to 52 +/- 16 cm.s-1 (P less than 0.01). These data demonstrate impaired diastolic filling after doxorubicin therapy at conventional dosages. PMID- 1936000 TI - Acute effects of gallopamil on left ventricular systolic and diastolic function in patients with ischaemic heart disease. AB - In 13 patients with chronic stable angina, left ventricular pressures were measured by catheter-tip micromanometer, and left cineventriculography was performed at matched atrial paced rates before and 20 min after administration of intravenous gallopamil (3 mg). Mean plasma concentration of gallopamil at the second haemodynamic and angiographic assessment was 18.6 +/- 5.7 ng.ml-1. Left ventricular peak systolic pressure decreased from 134 +/- 12 to 125 +/- 13 mmHg (P less than 0.005) and mean aortic pressure from 94 +/- 11 to 91 +/- 9 mmHg (ns). Peak positive first derivative of left ventricular pressure (+dP/dt) and maximal velocity of the contractile element (Vcemax) significantly decreased (from 1828 +/- 334 to 1702 +/- 304 mmHg.s-1, P less than 0.002, and from 51 +/- 11 to 43 +/- 5 s-1, P less than 0.001, respectively). Left ventricular protodiastolic pressure decreased from -0.6 +/- 2.9 to -2.8 +/- 2.9 mmHg (P less than 0.005) and left ventricular end-diastolic pressure from 9.5 +/- 3.4 to 8.9 +/- 4.6 mmHg (ns). No changes occurred in peak negative dP/dt, while a significant reduction was observed in the exponential time constant of the first 40 ms of isovolumetric relaxation (t-constant decreased from 38 +/- 8 to 34 +/- 7 ms, P less than 0.01). No changes were observed in end-diastolic and end-systolic left ventricular volume indices and ejection fraction. Thus, intravenous gallopamil induced a moderate afterload reduction and a slight negative inotropic effect resulting in a net effect of unchanged left ventricular pump function. The observed improvement of early relaxation seems to be a potentially beneficial effect of gallopamil in patients with coronary artery disease. PMID- 1936001 TI - Effects of nisoldipine on systolic and diastolic function in postinfarction patients with reduced left ventricular function: a randomized, double-blind, placebo controlled study. AB - The long-term effects of oral nisoldipine or placebo on clinical variables, exercise test results and echo Doppler-determined systolic and diastolic functions were studied in 30 consecutive patients with reduced left ventricular function (predischarge echocardiographic wall motion score greater than or equal to 8) following myocardial infarction. Groups were comparable in clinical variables, exercise results, echo Doppler measurements and coronary anatomy. During 6 months follow-up, death, reinfarction and bypass surgery or balloon angioplasty were equally distributed. A significant increase in exercise duration and time to onset of ST-depression was found in the nisoldipine treatment group, compared to the placebo group after 3 and 6 months. Time to onset of angina was not significantly different. Echocardiographic indices of left ventricular systolic function (ejection fraction and wall motion score) were unaltered; however, the time-velocity integral of the early diastolic filling phase and the early vs late diastolic flow velocity ratio were significantly increased while the atrial time-velocity integral vs total time-velocity integral was significantly decreased in the nisoldipine treatment group after 3 and 6 months of follow-up. In conclusion, nisoldipine reduced exercise-induced ischaemia, improved exercise capacity and diastolic left ventricular function in postinfarction patients with reduced left ventricular function. PMID- 1936002 TI - Serum lipids and lipoproteins in relation to restenosis after coronary angioplasty. AB - Restenosis after coronary angioplasty (PTCA) is a major problem, limiting the long-term efficacy of the procedure. Lipoprotein levels are associated with the development of atherosclerosis and may also be associated with restenosis. In this study the serum levels of cholesterol (CH), triglycerides (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were analysed in 157 patients undergoing 161 PTCA procedures. Follow-up coronary angiograms were performed after 6.0 +/- 4.3 months. The restenosis rate was 33%. Treatment with aspirin and a residual stenosis of 25-49% immediately after successful PTCA were the only variables associated with restenosis (P less than 0.05), otherwise the clinical and angiographic characteristics were similar with and without restenosis. There was no relationship between restenosis and the levels of CH, TG, HDL or LDL (P greater than 0.05). In univariate and multivariate analysis of males (n = 121) and females (n = 40) separately, restenosis was associated with low HDL in men and high HDL in women (P less than 0.05), but not with CH, TG or LDL (P greater than 0.05). We conclude that the serum levels of CH, TG and LDL do not seem to be related to restenosis after PTCA. It is suggested that low HDL in males and high HDL in females is related to restenosis. PMID- 1936003 TI - Importance of coronary spasm for recurrences following percutaneous transluminal coronary angioplasty (PTCA). AB - To examine the importance of coronary spasm for recurrences following coronary angioplasty, the incidence of spontaneous and ergonivine-provoked coronary spasm was studied, during initial and 6 months follow-up coronary angiography, in a consecutive series of 102 patients with single-vessel disease and successful coronary angioplasty. Repeat angiography demonstrated restenosis in 35 patients (34%). In patients with no demonstrable coronary spasm before and 6 months after PTCA, restenosis occurred in 23% (14/61). The recurrence rate for patients with spasms only before PTCA was similar (29%; 6/21). An increase of recurrences was observed in patients with coronary spasm before and 6 months after PTCA (69%; 9/13) and was extremely high in patients with detectable spasms only after PTCA (86%; 6/7). The importance of the severity of underlying coronary stenosis as regards the ergonovine testing result, demonstrated no relationship between the degree of underlying stenosis and the incidence of provokable coronary spasms. Thus, coronary spasms provokable only before PTCA do not increase the risk for recurrences. Spasms persisting after PTCA or seen only after the procedure are associated with a significantly higher rate of restenoses. PMID- 1936004 TI - Left hemitruncus in adulthood: diagnostic role of magnetic resonance imaging. AB - The diagnosis of left hemitruncus and large patent ductus arteriosus was made by magnetic resonance imaging in an adult patient with recurrent haemoptysis and dyspnoea on exertion. Previous cardiac catheterization and echocardiography failed to establish the complete diagnosis. Magnetic resonance imaging using spin echo and gradient-echo pulse sequences is a useful imaging modality to evaluate anatomical and functional abnormalities in patients with complex congenital heart disease. PMID- 1936005 TI - Myocardial infarction in a patient with factor XI deficiency and a lupus anticoagulant. AB - A 64-year-old man with both Factor XI deficiency and a lupus anticoagulant who suffered two myocardial infarctions within a 3-month period is described. Although thromboembolic disorders, including myocardial infarction, have been associated with the antiphospholipid syndrome, myocardial infarction in patients with Factor XI deficiency is rare. The potential role of Factor XIa in fibrinolysis is discussed. PMID- 1936006 TI - Intra-hisian 2:1 atrioventricular block secondary to Lyme disease. AB - We describe a case of Lyme carditis with intra-hisian 2:1 atrioventricular (AV) block documented by electrophysiological study. To our knowledge, only two cases of AV block at the level of the His bundle has been described in the literature. Sinus rhythm was restored after 4 days of i.v. ceftriaxone. PMID- 1936007 TI - Image quality and analysis in stress echocardiography. PMID- 1936008 TI - Affective disorders and survival after acute myocardial infarction. Results from the post-infarction late potential study. AB - Psychological data from 560 male survivors of acute myocardial infarction (AMI) were documented in the third week after onset of AMI. The psychodiagnostic assessment was designed to detect different forms of depression as well as hyperactive behaviour. A complete follow-up of these patients, which covers a period of 6 months, is available. Our findings indicate that affective disorders play an important role in the post-acute phase after AMI although the extent of myocardial infarction (as defined by an ECG score) and behaviour responses are not significantly related to one another. Different subforms of depression are not influenced by a history of angina pectoris, the degree and location of myocardial infarction, the occurrence of late potentials and age, whereas dyspnoea (P less than 0.001) and the recurrence of myocardial infarction (P less than 0.001) favour depressive mood states. Twelve cardiac deaths and 17 arrhythmic events occurred during the study period; they were significantly predicted by severe forms of post-AMI depression as revealed by univariate analysis. The evidence was stronger for predicting cardiac death (P less than 0.001) than for arrhythmic events (P = less than 0.035). The effect remains of borderline significance for cardiac death if all risk factors with a significant univariate influence are included in a multiple logistic regression model. The effect of depression is illustrated by Kaplan-Meier survival curves separated for patient groups with high as compared to low degrees of depression. Hyperactivity showed no impact on patient survival. PMID- 1936009 TI - Prehospital thrombolysis in acute myocardial infarction: the Belgian eminase prehospital study (BEPS). BEPS Collaborative Group. AB - Interest in early thrombolysis has prompted a study on the feasibility and time course of prehospital thrombolysis in patients with acute myocardial infarction (AMI) in six centres in Belgium. Patients with clinically suspected AMI and with typical ECG changes presenting within 4 h after onset of pain were treated with 30 units of Anisoylated Plasminogen Streptokinase Activator Complex (APSAC, eminase) intravenously by a mobile intensive care unit (MICU). Sixty-two patients were included in the study and an AMI was confirmed in 60. The mean time (+/- 1 SD) from onset of pain to injection of APSAC was 95 +/- 47 min and the mean estimated time gain, calculated as the time difference between the arrival of the MICU at home and the arrival of the MICU at the emergency department, was 50 +/- 17 min. In the prehospital period four patients developed ventricular fibrillation and one cardiogenic shock. During hospital stay severe complications were observed in four patients. Two events were fatal, one diffuse haemorrhage and one septal rupture; two events were non fatal, one feasible and that an estimated time gain of 50 min can be obtained. Potential risks and benefits remain to be demonstrated in a large controlled clinical trial. PMID- 1936010 TI - First myocardial infarction: 5-year survival predicted from routine clinical, laboratory, and radionuclide findings during the acute stage. AB - Five-year survival amongst 485 consecutive patients with their first acute myocardial infarction (AMI) was 78.2%. Univariate survival analysis showed that the following variables during the acute stage were of prognostic significance for survival: signs of left ventricular heart failure, enlarged cardiac volume, pulmonary congestion on chest X-ray, anterior myocardial infarction on ECG, and low left ventricular ejection fraction (LVEF), whereas enzyme analysis and Q/non Q signs on ECG were not. In the multivariate analysis two equivalent models were found. The first pinpointed age and LVEF as independent predictors of mortality, and the second age and left ventricular heart failure. Finally, our subcohort of patients aged less than the mean 63 years and with normal LVEF values of greater than or equal to 50%, or no left ventricular failure had an observed survival for 5 years close to an age- and sex-matched group from the Norwegian population. PMID- 1936013 TI - Pre-operative evaluation and therapy in mitral valve disease: surgery valvuloplasty. 18-19 October 1990, Paris, France. Proceedings. PMID- 1936011 TI - Serum creatine kinase and creatine kinase-MB isoenzyme activities in perinatally asphyxiated newborns. AB - Serum creatine kinase (CK) and creatine kinase-MB isoenzyme (CK-MB) activities were studied prospectively in serial blood samples obtained from 23 perinatally asphyxiated negroid newborns and 12 healthy controls during the first 100 h of life. The asphyxiated infants had significantly elevated mean CK and absolute CK MB but no fractional CK-MB activities. Peak mean CK and CK-MB values (U.l-1) were 789.17 (+/- 220), P less than 0.01 and 16.36 (+/- 3.0) P less than 0.001 respectively at the 6-8 post-partum period. The healthy controls, on the other hand, showed a steady decline in the activities of these enzymes from birth. The vaginally and operatively delivered asphyxiated infants showed significantly higher CK and CK-MB activities than their respective non-asphyxiated controls, but no increase in fractional CK-MB was recorded in any of the groups. The elevation in absolute and fractional CK-MB 42.0 U.l-1 (5.1%) in respect of the infants with TTI (transient tricuspid incompetence) was significant (P less than 0.05) when compared with the controls with features of TTN (transient tachypnoea of the newborn) in the 6-8 h post-partum period. One of the infants with TTI at autopsy had hypoxic myocardial injury. The specificity of CK-MB, as a marker of myocardial injury in asphyxiated negroid neonates, is plausible but remains uncertain. Until the lack of rise of CK and CK-MB in healthy negroid newborns is confirmed in a larger series with further studies on MM, BB and MB isoenzymes, caution is urged in the interpretation of elevated CK and CK-MB activities in asphyxiated negroid newborns. PMID- 1936012 TI - Differences in the antiischaemic effects of molsidomine and isosorbide dinitrate (ISDN) during acute and short-term administration in stable angina pectoris. AB - The acute and short-term effects of treatment with 10 consecutive doses of isosorbide dinitrate 40 mg t.i.d. and molsidomine 8 mg t.i.d. in slow release formulations were investigated in 10 patients with angiographically documented coronary artery disease and stable angina pectoris according to a randomized, double-blind, double-dummy, cross-over study design using conventional symptom limited exercise testing. Acute exercise testing 3 h following the first dose of ISDN and molsidomine showed a significant reduction of maximal ST segment depression and of the area above the ST segments. Time to occurrence of 0.1 mV ST segment depression, exercise duration, time to onset of angina and exercise tolerance increased significantly. On the fourth treatment day with ISDN and molsidomine an attenuation of these antiischaemic effects was seen. The mean effects on ST segment depression, area above ST segments, time to occurrence of 0.1 mV ST segment depression, exercise duration, time to onset of angina and exercise tolerance were reduced by 40%, 44%, 47%, 58%, 54% and 65%, respectively, in patients administered ISDN and by 33%, 48%, 58%, 59%, 45% and 60% in those given molsidomine. Thus, following sustained short-term therapy the antiischaemic effects of both drugs seem to be attenuated. In this report no marked differences were found between ISDN and molsidomine. PMID- 1936014 TI - Echo-Doppler quantitative assessment of non-ischaemic mitral regurgitation. AB - The reliability of non-invasive quantification of mitral regurgitation (MR) was assessed in 76 patients with angiographically demonstrated MR by comparing the results of different echo-Doppler (ED) indices with angiographic grade and MR fraction (MRF). Echo-Doppler studies were performed within 72h of right and left heart catheterizations in all patients. The following results were obtained: Transthoracic maximal relative jet area (RJA) is disappointing and differentiates only grade 1 from grade 4MR. RJA correlates better with haemodynamic data when obtained by transoesophageal echo: r = 0.78 versus r = 0.62, P less than 0.001. With the transoesophageal approach, a relative jet area greater than 50% and/or a jet width greater than 6 mm measured at the origin of the jet are strong indicators of severe MR. The ratio of mitral velocity time integral (VTI) to aortic VTI correlates with MRF: r = 0.77, P less than 0.001, n = 37. A VTI ratio greater than 1.3 identifies RF greater than 40% with a sensitivity of 80% and a specificity of 87%. A total inversion of the systolic wave of pulmonary venous flow is specific for grade 4 MR. The Doppler-derived MRF, correlates well with haemodynamic RF (r = 0.92, P less than 0.001, SEE: 7.5%). PMID- 1936015 TI - Quantification of mitral insufficiency by radionuclide techniques. AB - Radionuclide imaging is useful in the assessment of left and right ventricular function in patients with a variety of cardiac diseases. Measurements of particular interest in patients with mitral insufficiency concern the left ventricle: ejection fraction, end-systolic volume, end-systolic volume/end systolic pressure ratio, and the right ventricle (mainly its ejection fraction). The ejection and filling parameters of the left ventricle as well as parameters of the left atrial volume curve can also be of interest. Quantification of mitral insufficiency relies on comparisons of total stroke volume of the left ventricle, determined relatively, or quantitatively, with the forward stroke volume. The latter is measured either as the right ventricular stroke volume (in the absence of pulmonary and tricuspid regurgitation) or as cardiac output divided by heart rate and is obtained using a radionuclide or an independent method. Severe mitral regurgitation, as demonstrated by a large regurgitant fraction, can occur in the presence or absence of increased end-diastolic volume. The regurgitant fraction is not heart-rate dependent and does not clearly decrease during exercise, although some variations appear to exist. Evaluation of right ventricular function during exercise can also contribute to the assessment of patients with mitral insufficiency. Quantitative radionuclide methods are useful to assess the severity of mitral regurgitation and its repercussions. PMID- 1936016 TI - Left ventricular function in acute non-ischaemic mitral regurgitation. AB - Acute non-ischaemic mitral regurgitation (MR) has recently generated considerable interest because of its causal relationship to ruptured chordae tendineae and infective endocarditis, advances in its diagnosis by echo Doppler studies, and its management by afterload reduction and reconstructive surgery. It is fundamentally different from chronic MR because the previously normal, unprepared left ventricle (LV) and left atrium (LA) confront a sudden dramatic increase in volume. As the normal-sized left atrium suddenly receives a marked regurgitant flow, its pressure rises and is transmitted into the pulmonary capillaries causing pulmonary congestion and oedema. At onset, the LV function is usually well preserved and the pulmonary oedema does not reflect LV failure. In acute MR, the LV empties into the left atrium, thus reducing its radius and its systolic pressure, resulting in a decline in wall tension according to Laplace's law. With a reduction in LV wall tension, there is a marked increase in contractile shortening with marked increase in total LV output. The left ventricle may fail early in acute severe MR because it is forced to dilate rapidly before hypertrophy can occur, whereas in chronic MR both the LV diastolic volume and mass increase proportionately. With chronic persistence of MR, LV dysfunction and failure occur as a manifestation of the 'cardiomyopathy of overload'. Fortunately because of the low energy cost per unit of work in shortening, as opposed to that used for tension development, there is only a slight increase in myocardial oxygen consumption in acute MR. In patients with LV failure secondary to acute MR, the ejection fraction may be only slightly decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936017 TI - Aetiology of surgically treated mitral regurgitation. AB - The aetiologies of mitral regurgitation were reviewed in 336 patients operated on between 1970 and 1990. The relative frequency of rheumatic fever has decreased and the most common cause is now primary mitral valve prolapse (PMVP) which accounts for 60% of all patients. The increasing age of the surgical population seems to be one of the main factors of this change. Conservative surgical repair according to Carpentier's technique is now performed in 60% of all patients with mitral regurgitation and 80% of cases of PMVP. The aetiology of PMVP is still under discussion. Surgical description seems to indicate the existence of two different morphological aspects with significantly different rates and localizations of chordae ruptures, but our study failed to demonstrate any other anatomical, clinical or histological differences between the two groups. PMID- 1936018 TI - Right ventricular function in severe non-ischaemic mitral insufficiency. AB - Mitral insufficiency (regurgitation) is a disease of both ventricles. To determine the pathophysiological implications and clinical value of assessment of right ventricular function in this disease, right ventricular ejection fraction was determined by radionuclide cineangiography (r = 0.73, P less than 0.01, vs contrast angiography, n = 30) in patients with severe, non-ischaemic mitral regurgitation. Among 31 patients with isolated mitral regurgitation treated medically, five died, all within 2 years of follow-up; all five were among the eight patients with left ventricular ejection fraction less than or equal to 45% (lower limit of normal), and among the six patients with right ventricular ejection fraction less than or equal to 30% (almost invariably associated with at least mild pulmonary hypertension). During the same period, valve replacement was performed in 22 patients with isolated mitral regurgitation; among the six patients with right ventricular ejection fraction less than or equal to 30% before operation, only one died (P less than 0.05), indicating the risk mitigating effect of valve replacement. Among eight pre-operative patients with combined mitral and aortic regurgitation, four died within 7 years after double valve replacement; all patients with right ventricular ejection fraction during exercise less than 20% died. After mitral valve replacement for isolated mitral regurgitation, right ventricular ejection fraction improved rapidly (average 8% in less than 1 year (P less than 0.05); 3% more at 3 years after operation (P less than 0.05)). Post-operative symptom persistence was predictable from ventricular ejection fraction before operation less than 30% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936019 TI - Intra-operative transoesophageal echocardiography after mitral repair--specific conditions and pitfalls. AB - The aim of this study was to determine the specific conditions and pitfalls of immediate assessment of the reconstructed mitral valve in open chest patients. Sixty-two patients had a mitral reconstruction controlled by transoesophageal echocardiography and colour Doppler (TEE) from the moment when cardiac activity restarted under extracorporeal circulation (ECC), until complete rewarming of the patient and weaning off the by-pass. The following conditions altered the imaging quality: (1) dried probe in the oesophagus or air bubbles, (2) non-aspirated air from the stomach, (3) small or empty left atria, (4) invagination of the left atrial appendage, (5) trapped air in the posterior pericardium, (6) spontaneous contrast. Transient mitral regurgitation disappeared completely in 12/62 patients: five had temporary impairment of LV function, two had reduced filling of the heart, one had left ventricular outflow obstruction exacerbated by isoproterenol and nitroglycerin, two had ventricular ectopic rhythms, and two epicardial pacing. Only one of the 62 patients had persistent significant MR which required a second run of ECC. We conclude that mitral regurgitation after mitral valve repair is closely related to the quality of LV function. A decision to reoperate should eliminate the possible pitfalls, and take into consideration the specific conditions of immediate postoperative cardiac function. PMID- 1936020 TI - Mitral valve repair for mitral insufficiency. AB - Degenerative mitral valve disease has become the major cause of mitral regurgitation in North America; it is incumbent on surgeons to know repair techniques and to document their results. Fortunately, improvements in myocardial protection have been concurrent with the evolution of mitral valve repair in our country. The steep learning curve may be traversed, and the majority of degenerative mitral valves may be successfully repaired. Serial echo Doppler studies provide documentation of successful repair and monitor the patient's progress objectively. Echocardiography also provides a forum for communication between surgeons and cardiologists and, for the first time, the presence and amount of residual mitral regurgitation can be quantitated. PMID- 1936021 TI - A feasibility study of valve repair in rheumatic mitral regurgitation. AB - Valve repair is an established form of treatment for mitral valve regurgitation. In order to elucidate the feasibility and results of aggressive repair in a young rheumatic population, all consecutive patients operated on between July 1988 and July 1990 for mitral regurgitation were reviewed. There were 203 patients with a mean age of 29 years; 91% were in functional classes III-IV. Pure regurgitation was present in 47.8%. Associated valvular surgery was performed in 56.2%. Forty nine (24.1%) patients had a straight valve replacement (MVR), 18 (8.9%) had an unsuccessful attempt at repair and in 136 (67%) the repair was considered successful. Overall hospital mortality was 3.4%: 4% for MVR, 16.6% for the attempts, 1.4% for repairs. The thromboembolic rate for replacement was 6.0% pt yr and for repair 0.87% pt-yr. There were five late deaths in the replacement group and one in the repair group. Seventeen patients required reoperation in the repair group (12.6%) with a mean age of 17 years. Six of these patients had active rheumatic carditis, either at first operation or in the postoperative period. The postoperative functional status of all patients was excellent. In conclusion, valve repair although possible in a high percentage of rheumatic regurgitation patients carried a penalty of unsuccessful attempts and reoperations. However, in the follow-up period the rate of thromboembolism and late mortality among the patients with prostheses offsets these disadvantages. PMID- 1936023 TI - Valve replacement with bioprostheses for non-ischaemic mitral insufficiency. AB - From 1976 to 1989, 122 patients underwent isolated mitral valve replacement with a bioprosthesis for non-ischaemic mitral insufficiency. There were 76 women and 46 men, with a mean age of 52 years. Mitral valve disease was of rheumatic origin in 71 (58%), due to myxomatous degeneration in 50 (41%), and congenital in one. Early mortality was 3.3% (4 pts). The 10-year survival was 65 +/- 7%. A follow-up was available for all 122 patients, averaging 78 months, for a total of 763 patient-years. Valve-related (VR) complications included: 16 thromboembolic episodes in 13 patients (2.1% pt-yr), 3 endocarditis in 2 patients (0.4% pt-yr), and 20 reoperations (2.6% pt-yr), 19 of which were due to intrinsic structural deterioration of the tissue valve. There was no haemorrhagic episode. Overall, 32 patients suffered a VR complication (4.2% pt-yr). The 10-year freedom rates from haemorrhage, endocarditis, thromboembolism, and reoperation were 100%, 98%, 87%, and 64% respectively. After 10 years, 87% of the patients were free from VR mortality, 84% were free from VR mortality and permanent disability, and 52% remained free from all VR complications. While 69% of the patients (84 pts) were in functional class III or IV preoperatively, 89% (102 pts) of the survivors were in class I or II after operation. Excellent survival and clinical results have been obtained with the use of bioprostheses in this disease. However, because durability beyond 10 years appears to be limited and the cause of major morbidity, tissue valves are now used more selectively. PMID- 1936022 TI - Long-term results of mitral valve repair for non-ischaemic mitral regurgitation. AB - One hundred and fifty-five patients with isolated mitral regurgitation were referred from our cardiology department for mitral valve repair between 1972 and 1990. Men were predominant (59%), mean age was 51 years, and 61% of the patients were in NYHA class III or IV. Degenerative aetiology was predominant (65%). Surgical repair was performed according to the Carpentier techniques. Two operative deaths occurred (1.3%). The survivors were followed-up for an average of 4 years, and the rates of survival and good functional results at 11.5 years, were respectively 84.5% and 64.5%. The linearized rates of endocarditis, thromboembolic events and re-operations were respectively 0.35%, 1.54% and 2.05% pt-yrs. Residual mitral regurgitation was looked for by clinical and Doppler examination: there was no regurgitation in 55.5% of patients, mild regurgitation was found in 26%, moderate in 10.3% and severe in 8.2%. Analysis of moderate and severe residual regurgitation identified three promoting factors: rheumatic origin of the regurgitation, surgery of the anterior leaflet and time of surgery (the incidence after surgery has been lower in recent years). Other 'less well known' complications were encountered: left ventricular outflow tract obstruction, progressive evolution towards mitral stenosis, appearance of aortic regurgitation and formation of left atrial thrombi. Despite these complications, we must stress the satisfactory results of the technique, in particular in mitral valve endocarditis; 22 patients were operated on for this reason, six during the acute phase of the disease, and no surgical death, or recurrence of endocarditis, and only one case of severe residual regurgitation was observed. PMID- 1936024 TI - Left ventricular function after surgical correction of chronic mitral regurgitation. AB - It is generally believed that mitral regurgitation (MR) creates a systolic 'unloading' effect by providing a low-resistance ejection into the left atrium; this is thought to increase the left ventricular ejection fraction (EF), and thus to mask a reduced contractile state. Similarly, mitral valve replacement (MVR), by removing the low-resistance regurgitant leak, has been thought to increase left ventricular afterload (systolic wall stress) and thereby cause the decrease in EF that is often seen postoperatively. These concepts have never been confirmed in patients with chronic MR. Accordingly, we evaluated systolic wall stress before and after MVR and assessed stress-shortening relations in two groups of patients with chronic MR (those with compensated and those with decompensated MR). Calculated values for circumferential and meridional wall stress were found to be normal or high in patients with chronic MR. This indicates that chronic MR is not associated with an unloading effect. In decompensated MR, systolic wall stress tends to increase after MVR; this can contribute to a postoperative decline in myocardial fibre shortening and a lower EF. By contrast, patients with compensated MR exhibit a decline in systolic wall stress after MVR; despite this postoperative decline in afterload, fibre shortening falls. This indicates that the fall in fibre shortening after MVR is not the result of increased systolic loading. In such patients, the valve replacement (with loss of integrity of papillary muscles and chordae, and a tethering of posterobasal wall motion by the prosthesis) is most likely responsible for the postoperative decline in fibre shortening and EF. PMID- 1936025 TI - Natural history of severe mitral regurgitation. AB - The aim of this retrospective study was to review the outcome of 216 patients (pts), investigated for severe mitral regurgitation (MR) between January 1980 and December 1987. Definition of 'severe' was mainly clinical: MR sufficiently advanced for the cardiologist to investigate whether surgery should be imminent. One hundred and sixty two pts (group 1) were operated on; 54 (group 2) did not undergo surgery. Baseline characteristics were similar in the two groups, except for aetiology (less dystrophic and more ischaemic MR in group 2), functional class (88.3% class III or IV in group 1 vs 48.1% in group 2; P = 0.001), pulmonary pressures (lower in group 2) and left ventricular ejection fraction (group 1: 0.66 +/- 0.13; group 2: 0.56 +/- 0.17; P = 0.001). Mean follow-up after hospital admission or surgery was comparable in the two groups (group 1: 3.9 +/- 2.5 years; group 2: 3.5 +/- 2.7 years). Three pts (group 2) were lost to follow up. Sixty-three pts died; 35 of the 162 operated on; 28 of the 54 non-operated on. Actuarial survival rate at 8 years was 74.0 +/- 4.3% in group 1 vs 33.2 +/- 9.2% in group 2 (P = 0.001). These results confirm that the prognosis of severe MR is poor if it is not operated on, whereas the postoperative course of severe MR, when operated on in time, is good. PMID- 1936026 TI - Indications for surgery in mitral regurgitation. AB - Present day indications for surgery in mitral regurgitation have to take into account changes in aetiology, advances in pre-operative evaluation of mitral lesions, technical progress in mitral valve repair and better knowledge of pre operative predictive factors of surgical results. The results of a series of 294 patients operated on between 1970 and 1990 show that surgery is advisable before patients reach Functional Class III or IV, and before they develop atrial fibrillation, an ejection fraction of under 0.55, or marked left ventricular and atrial enlargement. Surgical indications depend on two factors: the possibility of valve repair evaluated by transthoracic and transoesophageal echocardiography, and the experience of the surgical team in this kind of surgery. Valve repair is the best treatment in many patients, particularly those with degenerative valve lesions, poor ejection fraction, elderly people and some cases of infective endocarditis. PMID- 1936027 TI - Pathomorphological aspects, aetiology and natural history of acquired mitral valve stenosis. AB - Commissural fusion, leaflet thickening and alteration of the subvalvular apparatus are dominant mechanisms causing clinically important mitral stenosis (MS) of rheumatic origin. Calcification and a consequent decrease in leaflet mobility are subsequent features in rheumatic MS and may be the primary mechanisms in MS of degenerative origin. In 1051 consecutive patients with pure or predominant MS requiring surgical intervention, aetiology was rheumatic in 76.9%, infective in 3.3%, degenerative (severe annular and leaflet calcification) in 2.7% and congenital (Lutembacher syndrome) in 1.2%; it was the result of systemic lupus erythematosus (n = 4), carcinoid heart disease (n = 2), endomyocardial fibrosis (n = 2) and rheumatoid arthritis (n = 2) in less than 1%, while in 14.5% of these patients aetiology remained unclassified. The natural history of rheumatic MS is characterized by an asymptomatic latent period, following the initial rheumatic fever (RF). In a prospective study of MS (n = 159) the mean interval between RF and the appearance of symptoms was 16.3 +/- 5.2 years. Twenty-five years after the initial RF 8% of the patients were still asymptomatic, 9% were class II (NYHA), 33% class III and 50% had been operated or were class IV. Progress from mild to severe disability took 9.2 +/- 4.3 years on average. When valve surgery was indicated but refused by the patients, survival with medical treatment was 0.44 +/- 0.06 after 5 years, 0.32 +/- 0.08 after 10 years and 0.19 +/- 0.09 after 15 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936028 TI - Transoesophageal echocardiography in the assessment of percutaneous mitral commissurotomy. AB - The aim of this study was to assess the value of transoesophageal echo (TEE) in comparison with transthoracic echocardiography (TTE) in selecting candidates and evaluating the results of percutaneous mitral commissurotomy (PMC). One hundred and ten patients (pts) were examined by TEE and TTE before PMC. PMC was not performed in eight pts who had a thrombus in the left atrium detected by TEE but not by TTE. Out of the 102 other pts, TEE was better than TTE in detecting mild mitral regurgitation (MR) (84 vs 38, P less than 0.01). Spontaneous contrast was only shown by TEE in 70 pts. On the other hand, planimetry of the valvular area was only possible with TTE. This technique was also better in the assessment of the commissural area. During PMC, TEE enabled the interatrial septum to be punctured in two pts. After PMC, MR was trivial in 49 TEE cases compared with 36 by TTE and was moderate in 20 TEE pts compared with 12 by TTE (P less than 0.02). Transoesophageal colour Doppler showed a trivial atrial shunt in 63% of cases vs 13% by TTE (P less than 0.01).A small atrial septal defect was found in 30 cases only by TEE, and a spontaneous contrast persisted in all pts but six with moderate MR. In conclusion, TEE provides useful information in the ultrasonic assessment of PMC in particular with left atrial thrombi, mitral regurgitation, and the post PMC atrial septal defect. However, both methods are complementary and only TTE enables calculation of valve area. PMID- 1936029 TI - Left ventricular function in rheumatic mitral stenosis. AB - Haemodynamic factors contributing to clinical disability in patients with rheumatic mitral stenosis have been under discussion and investigation for decades. Prior to the development of left heart catheterization, a low cardiac output in the presence of little or no pulmonary hypertension was taken as evidence for a myocardial 'insufficiency'. With the use of left heart catheterization, it was possible to exclude the presence of coronary artery disease and to assess directly the size and function of the left ventricle. Such studies indicate a tendency toward low-normal left ventricular end-diastolic volumes and low-normal ejection fractions. Modest reductions in the ejection fraction may be due to: (1) a restriction or tethering of posterobasal myocardium by the scarred mitral apparatus, or (2) abnormal interventricular septal motion related to right ventricular overload and unequal filling of the two ventricles. These and other factors, such as limited LV distensibility and variable diastolic suction, may affect ventricular function in rheumatic mitral stenosis. Thus, left ventricular dysfunction can generally be explained without implicating a rheumatic myocardial factor. PMID- 1936030 TI - Diagnosis of left atrial thrombi in mitral stenosis--usefulness of ultrasound techniques compared with other methods. AB - The purpose of this study was to evaluate various methods of diagnosis of left atrial thrombi (LAT) in patients (pts) with mitral stenosis (MS). From 1980 to 1990, 581 pts with MS have undergone open mitral commissurotomy (n = 169) or valve replacement (n = 412). All pts had transthoracic 2D echocardiography (TTE), 101 transoesophageal echocardiography (TEE), 192 a left atrial angiography (A) (from a left ventricular injection if associated mitral regurgitation grade 3 (n = 154) or from an injection in the pulmonary artery (n = 38) and 229 a coronary angiography (CA). Tomodensitometry (TD), nuclear magnetic resonance (NMR) and 111 Indium platelet imaging (IPI) were performed in some cases, 2, 8 and 5 respectively. All these examinations were carried out in the month before surgery. LAT was found by the surgeon in 43 pts (7%). The site was left atrial appendage in 26 cases (60%) and left atrial cavity in 17 cases. Sensitivity (Se), specificity (Sp) of TTE/TEE/A/CA were the following: TTE, Se% 28, Sp% 99; TEE, Se% 83, Sp% 97; A, Se% 28, Sp% 99; CA, Se% 14, Sp% 100. Specificity was high with all methods but sensitivity was high only with TEE and poor with other methods because of difficulty in detecting thrombi of the left atrial appendage. Specificity and sensitivity of TD, NMR and IPI require more information. False negative cases are possible with NMR (1 case) and IPI (1 case) in well established LAT. We conclude: TEE is the easiest way to detect LAT, particularly when located in the left atrial appendage. It should be carried out systematically before percutaneous mitral valvuloplasty or surgery. PMID- 1936032 TI - Does mitral stenosis need invasive investigation? AB - Evaluation without catheterization of patients with valvular heart disease implies that diagnosis based upon non-invasive techniques alone are qualitatively and quantitatively correct. The diagnosis should indicate not only the valvular lesion in question but should give information about associated conditions that could influence management decisions (whether to operate or not or whether to modify the intended operation). A review of the literature shows that in mitral stenosis (MS), both pressure gradient and valve area can be obtained non invasively (rest/exercise). These data, combined with the ultrasound appearance of the valve, subvalvular apparatus, chamber sizes, assessment of associated regurgitation and eventual pulmonary hypertension, permit a complete evaluation of the MS patient. Thus, it can be concluded that in experienced hands, the large majority of patients with MS can be assessed reliably non-invasively for clinical screening and for valve surgery. Excluding those in whom coronary angiography is mandatory, cardiac catheterization should be required only infrequently (in less than 10%). Cardiac catheterization should, however, be carried out in patients in whom technical reasons make ultrasound examinations incomplete (obesity or respiratory disease), and in patients in whom there is a discrepancy between the physical signs and the Doppler ultrasound. PMID- 1936031 TI - Influence of associated valvular lesions on long-term prognosis of mitral stenosis. A 20-year follow-up of 202 patients. AB - Other valvular lesions associated with pure MS were studied in 202 consecutive patients whose mean age was 43.4 +/- 12.7 years; 76.7% were females. MS was isolated in 63.4%, associated with aortic regurgitation (AR) in 27.7%, aortic stenosis in 1.0%, tricuspid stenosis (+aortic valve lesion) in 1.0%. In isolated MS, 42.4% were NYHA class III or IV, compared with 49.0% in MS + aortic valve lesion. One hundred and sixty-nine (85.4%) patients were operated on; 23.1% had mitral valve replacement, 76.9% had closed (31.4%) or open (45.6%) mitral commissurotomy; 7.1% had associated aortic valve replacement. There were perioperative complications in 20.4%, and the perioperative death rate was 4.1%. Two patients were reoperated in the postoperative course, and 28 patients after this period. The follow-up was 13.3 +/- 4.5 years. The survival rate was 77.7 +/- 4.6% (SE) for isolated MS, and 71.1 +/- 6.3% for MS associated with an aortic valve lesion (NS). The prognosis of MS is very good: the survival rate at 20 years follow-up is 75%. The association of aortic stenosis or tricuspid stenosis does not appear to alter this survival, but numbers are small. Important aortic regurgitation is a significant predictor of higher mortality in patients with MS. PMID- 1936033 TI - Immediate and mid-term results of percutaneous mitral commissurotomy. AB - The results of percutaneous mitral commissurotomy (PMC) were assessed in a series of 600 patients (pts) with mitral stenosis. Their mean age was 43 +/- 15 years (13-86). One hundred and eight had had a previous surgical commissurotomy; 464 were in NYHA class III or IV; atrial fibrillation was present in 188. One hundred and fifty-nine had valvular calcification and angiography disclosed a mild regurgitation (MR) (1/4) in 255. Technical failure occurred in 19 pts. In the remainder, PMC improved valve function: valve area (VA) increased from 1.1 +/- 0.3 cm2 to 2.2 +/- 0.5 cm2 (P less than 0.0001) as assessed by haemodynamics, and from 1 +/- 0.2 to 2 +/- 0.4 cm2 (P less than 0.0001) as assessed by two dimensional echocardiography. Complications were as follows: death (0.5%), haemopericardium (0.8%), severe MR (3.8%), embolism (3.3%), atrial shunt (14%). Secondary surgery for complications following PMC was necessary in 4.8% of cases. There were poor results (VA less than 1.5 cm2 and/or MR greater than 2/4) in 13%; their predictors being valve anatomy (P less than 0.001), initial valve area (P less than 0.01) and previous surgical commissurotomy (P less than 0.05). Among the 437 pts resident in France, 98% were followed-up 15 +/- 11 months after PMC (range 1-48). After 42 months, the actuarial rates of survival, freedom from need for reoperation and good functional results were respectively: 87 +/- 6%, 81 +/- 3% and 72 +/- 6%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936034 TI - Percutaneous mitral valvulotomy in non-optimal candidates. AB - From 1987 to 1990, 215 patients aged 53 +/- 13 years underwent percutaneous mitral valvulotomy in our institution. Mean gradient dropped on average from 13 +/- 4 to 5 +/- 2 mmHg and mitral valve area increased from 1.0 +/- 0.26 to 1.97 +/- 0.5 cm2 at the end of the procedure. Good results, defined as mitral valve area greater than or equal to 1.5 cm2 and mitral regurgitation less than or equal to 2+ at the end of the procedure, were obtained in 78% of the cases. In 41 patients with a poor anatomical form of mitral stenosis, mean gradient decreased from 12 +/- 3 to 6 +/- 6 mmHg and mitral valve area increased from 1.0 +/- 0.3 to 1.7 +/- 0.5 cm2. Good results were obtained in only 50% of the patients. One third of the 3+ mitral regurgitation occurred in this subgroup of patients. In patients with prior surgical commissurotomy, in elderly people and in patients with associated valvulopathy or prosthetic aortic valve, the success rate was similarly low. A significant inverse relationship was found between X-ray and echo scores on the one hand and mitral valve area at the end of the procedure on the other, thus confirming that the results of percutaneous mitral valvulotomy are related to the anatomical form of mitral stenosis. However, patients with poor anatomical forms can undergo the procedure with an acceptable risk compared to benefit ratio. PMID- 1936035 TI - Treatment of mitral stenosis. AB - In patients with mitral stenosis the need for therapeutic intervention can be assessed by clinical and non-invasive data. Mitral valve replacement is indicated when marked dyspnoea on mild exertion, dyspnoea at rest or pulmonary oedema, haemoptysis, atrial fibrillation, recurrent systemic emboli or right ventricular failure occur in a patient with a mitral valve area of less than 1.5 cm2, as measured by Doppler echocardiography. This treatment will entail life-long anticoagulation in the majority of patients. Closed commissurotomy is no longer considered a valid therapeutic alternative due to its limited success rate but open commissurotomy and balloon valvotomy may be performed in patients with no significant calcification of valve cusps and no major concomitant mitral regurgitation. Preservation of the subvalvular apparatus and left ventricular geometry can be considered the most important advantages of these techniques. More severe chronic symptoms are generally required as indication for mitral valve replacement because of the additional long-term imponderabilities imposed by an implanted artificial device. Therefore, in patients with mitral stenosis different symptoms and clinical findings will eventually lead to different interventions. PMID- 1936036 TI - Percutaneous transvenous mitral commissurotomy using the Inoue balloon. AB - The Inoue balloon catheter is unique in function as well as shape, and can be especially adapted for each patient to ensure a high success rate and low morbidity during percutaneous transvenous mitral commissurotomy (PTMC). Before transseptal puncture, right atrial angiography is performed to image the proper point of puncture to avoid not only accidental perforation but also the difficulty of balloon insertion into the mitral orifice. There are two main techniques for inserting the balloon into the mitral orifice. One is a direct method, and the other is loop formation in the left atrium. Balloon selection is basically standardized by patient height; 30 mm for a height of greater than 180 cm, 28 for greater than 160, 26 for greater than 147, 24 for less than 147. However, it should be smaller in valves with severe pathological changes, to prevent mitral regurgitation especially in valves with a mix of strong and weak echoes in the leaflets, combined with strong echo in the commissures shown on 2 dimensional echo-cardiography. For a patient at an advanced age, a smaller balloon should be chosen. A stepwise dilatation technique is effective for preventing the creation of severe mitral regurgitation. Doppler echo-cardiography should be used to decide whether further dilatation is necessary. This will estimate resultant mitral regurgitation, increased mitral valve area and degree of commissure separation. The disappearance of the balloon waist under fluoroscopy is also important in decision making. PTMC is a treatment of choice for mitral stenosis except for fresh mural thrombus and combined severe mitral regurgitation. PMID- 1936037 TI - Should platelets be labelled in plasma or saline? Consider the clinical indication. PMID- 1936038 TI - Dosimetry of iodine 131 metaiodobenzylguanidine for treatment of resistant neuroblastoma: results of a UK study. AB - In 1987, the United Kingdom Children's Cancer Study Group (UKCCSG) set up a multi centre study to investigate the toxicity of iodine 131 metaiodobenzylguanidine (mIBG) in the treatment of resistant neuroblastoma. Since December 1987, 25 children suffering from neuroblastoma have been treated with 131I-mIBG at six UK centres. All centres followed standardised physics and clinical protocols to provide consistent toxicity and dosimetry data. These protocols describe the methods employed for both the tracer study using 131I-mIBG and the subsequent therapy. Whole-body dosimetry calculations were performed on data from the tracer study. The activity administered for therapy was the amount predicted to deliver a predefined whole-body dose. Estimates of doses delivered to various organs during treatment are given in Table 1. PMID- 1936039 TI - Can technetium 99m bisdiethylphosphinoethanebis-t butylisocyanide (99mTc-DEPIC) be used for routine radionuclide ventriculography? AB - Radionuclide ventriculography is a useful investigation in the evaluation of cardiac function. Generally, in vivo technetium 99m-labelled red blood cells (RBC) yield good quality images in ventriculography. However, it is widely believed that some drugs have an adverse effect on RBC labelling. Zanelli et al. (1987) developed a radiopharmaceutical (technetium 99m bis diethylphosphinoethanebis-t-butylisocyanide, 99mTc-DEPIC) to obtain better results in patients using such drugs. We undertook a prospective study of 6 patients with cardiovascular and/or pulmonary disease using several kinds of drugs to evaluate imaging of the cardiac blood pool with 99mTc-DEPIC and in vivo labelled 99mTc-RBC. After injection, blood samples were taken, and gated equilibrium blood pool studies were performed. The radiochemical purity of the injected 99mTc-DEPIC varied from 76.4 to 93.6% (mean 86.4%, SD 5.7%). The protein (pre-albumin) binding was 100%. Biological half-life in blood varied from 3.3 to 4.7 h (mean 4.1 h, SD 0.5 h). For 99mTc-RBC no significant blood disappearance was seen for 8 h. The percentage of RBC-bound 99mTc varied from 96.9% to 98.3% (mean 97.0%, SD 0.5%) and was stable for at least 8 h. The heart-to-lung, heart to-spleen, and heart-to-liver ratios were higher for 99mTc-RBC than for 99mTc DEPIC. Furthermore, 99mTc-DEPIC showed a significant decline of the ejection fraction with time. Visually, the images with 99mTc-RBC were superior to those with 99mTc-DEPIC, especially a few hours after injection. According to our findings, in vivo labelling of 99mTc-RBC is still the method of choice for routine radionuclide ventriculography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936040 TI - Detection of deep venous thrombosis with indium 111-labelled monoclonal antibody against tissue plasminogen activator. AB - The administration of a radiolabelled monoclonal antibody against tissue plasminogen activator allows detection of areas with increased fibrinolytic activity, i.e. those with an active thrombotic lesion. Eight patients with phlebographically verified deep venous thrombosis were examined. At the time of immunoscintigraphy study they were examined receiving anticoagulant therapy. Some 75-85 MBq indium 111-labelled antibody were injected, and scintigrams were obtained after 30 min and after 24 h. The precise site of the thrombus could not be visualized after 30 min due to high background activity, whereas after 24 h it was detectable in all patients. The thrombus/background ratios achieved are twice as high as those observed in a human antifibrin antibody study. These preliminary data suggest a high sensitivity of our t-PA-specific antibody for the detection of active deep venous thrombosis in man, and our antibody seems to offer theoretical advantages over both platelet and fibrin-specific antibodies. PMID- 1936041 TI - Functional alterations of human platelets following indium-111 labelling using different incubation media and labelling agents. AB - Human platelets were labelled in the absence or presence of plasma using indium 111 labelled oxine sulphate, tropolone or 2-mercaptopyridine-N-oxide (MPO). Under in vitro and in vivo conditions, platelet functions were evaluated by measuring their aggregability, survival, recovery and early distribution. High labelling efficiency was achieved in saline labelling, whereas with plasma labelling, it was necessary to concentrate the platelet-rich plasma to 4.8 x 10(6) platelets/microliters. The aggregation of platelets labelled in plasma or saline was compared with that of controls; platelets labelled in saline showed lower aggregability in 2 microM ADP but not in 5 microM ADP nor with collagen. No significant differences in platelet survival and recovery were noted between platelets labelled in plasma and those labelled in saline. Our results indicate that partial loss of ADP aggregability in vitro does not influence the in vivo viability of platelets labelled in saline. Scintigraphic studies showed that platelets labelled in a saline medium were temporarily sequestrated in the liver but not in the spleen or heart. Thus, platelet labelling in saline does not affect platelet function adversely, but platelets labelled in plasma are more desirable for assessing the early distribution of platelets in the reticuloendothelial system. PMID- 1936042 TI - Effects of tumour mass and circulating antigen on the biodistribution of 111In labelled F(ab')2 fragments of human prostatic acid phosphatase monoclonal antibody in nude mice bearing PC-82 human prostatic tumour xenografts. AB - We have evaluated the effects of tumour mass and circulating antigen (prostatic acid phosphatase, PAP) on the biodistribution and the incorporation of 111In labelled F(ab')2 monoclonal antibody (MoAb) fragments directed against human PAP into human prostatic tumours (PC-82; 0.1-8.9 g) growing in nude mice. The radioactivities in the blood, liver, spleen, kidney and tumour were compared at 1, 3, 4 and 6 days after the intravenous administration of the antibody fragments. There was a significant correlation between the tumour size and the serum PAP concentration in the model employed. Even tissue of a small tumour (less than 0.1 g) had a high concentration of PAP, but it was not secreted into the circulation in detectable amounts when measured by radioimmunoassay (the lowest standard was 0.5 micrograms/l). The percentage uptake by tumours of the injected dose per gram of tissue (%ID/g) was inversely proportional to the tumour size at 24 h after the administration of 111In-labelled F(ab')2 fragments. This relationship had levelled off by 72 h and most likely reflected a better vascularisation of the smaller tumours. Our results show that the increase in tumour size and in the concentration of circulating antigen in the blood led to decreased tumour-to-blood ratios, since there was a tendency for higher blood activities in mice with larger tumours and higher serum PAP concentrations. There was no correlation between tumour size and label uptake by the liver during the follow-up over 144 h, although serum PAP concentrations ranged from 3.1 micrograms/l to 352 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936043 TI - Effect of loperamide and delay of bowel motility on bile acid malabsorption caused by late radiation damage and ileal resection. AB - Selenium-75 homocholic acid conjugated with taurine (75Se-HCAT) was used during loperamide administration in seven patients suspected of having bile acid malabsorption due to late radiation damage and small-bowel resection in order to document the aetiology of ileal dysfunction and to adjust therapeutic management. In two patients with ileal resection up to 50 cm and in one patient without resection, a reduction of bowel motility by loperamide resulted in marked normalization of the 75Se-HCAT retention measurements. Sequential scintigraphic 75Se-HCAT imaging demonstrated a significant improvement in the 75Se-HCAT reabsorption and recirculation, accompanied in one case by prolongation of colonic retention of the radiopharmaceutical. In four patients with more than 80 cm resection, the 75Se-HCAT test was abnormal during loperamide administration. In two of these patients for whom baseline values were available, no improvement in the pattern of 75Se-HCAT absorption was observed. In conclusion, the first results of loperamide 75Se-HCAT in patients suspected of having bile acid malabsorption and abnormal baseline 75Se-HCAT are promising. Intervention with loperamide is easy and seems to improve the clinical value of the test with direct therapeutic implications. Sequential 75Se-HCAT imaging is essential for interpreting changes in the 75Se-HCAT retention measurements. PMID- 1936044 TI - Mathematical modelling in nuclear medicine. AB - Modern imaging techniques can provide sequences of images giving signals proportional to the concentrations of tracers (by emission tomography), of X-ray absorbing contrast materials (fast CT or perhaps NMR contrast), or of native chemical substances (NMR) in tissue regions at identifiable locations in 3D space. Methods for the analysis of the concentration-time curves with mathematical models describing the physiological processes and the appropriate anatomy are now available to give a quantitative portrayal of both structure and function: such is the approach to metabolic or functional imaging. One formulates a model first by defining what it should represent: this is the hypothesis. When translated into a self-consistent set of differential equations, the model becomes a mathematical model, a quantitative version of the hypothesis. This is what one would like to test against data. However, the next step is to reduce the mathematical model to a computable form; anatomically and physiologically realistic models account of the spatial gradients in concentrations within blood tissue exchange units, while compartmental models simplify the equations by using the average concentrations. The former are known as distributed models and the latter as lumped compartmental or mixing chamber models. Since both are derived from the same ideas, the parameters are usually the same; their differences are in their ability to represent the hypothesis correctly, quantitatively, and sometimes in their computability. In this essay we review the philosophical and practical aspects of such modelling analysis for translating image sequences into physiological terms. PMID- 1936046 TI - Nuclear medicine and medical literature. PMID- 1936045 TI - Excretion of technetium 99m hexakismethoxyisobutylisonitrile in milk. AB - The amount of radioactivity excreted in breast milk following the administration of technetium 99m hexakismethoxyisobutylisonitrile (99mTc-MIBI) to a patient referred for cold spot myocardial scintigraphy was determined. During the first 24 h after administration, only 41.2 kBq 99mTc (0.0084% of the injected dose) was excreted in 448 ml milk with the highest concentration of 0.49 kBq/ml in the first sample. The images obtained show a high concentration of 99mTc-MIBI in the lactating breasts contrary to the very small percentage excreted in the milk. Comparison with various recommendations regarding nursing after administration of radiopharmaceuticals seems to indicate that the administration of 99mTc-MIBI does not necessitate an interruption of breast-feeding. PMID- 1936047 TI - Perceptual and statistical analysis of cardiac phase and amplitude images. AB - A perceptual experiment was conducted using cardiac phase and amplitude images. Estimates of statistical parameters were derived from the images and the diagnostic potential of human and statistical decisions compared. Five methods were used to generate the images from 75 gated cardiac studies, 39 of which were classified as pathological. The images were presented to 12 observers experienced in nuclear medicine. The observers rated the images using a five-category scale based on their confidence of an abnormality presenting. Circular and linear statistics were used to analyse phase and amplitude image data, respectively. Estimates of mean, standard deviation (SD), skewness, kurtosis and the first term of the spatial correlation function were evaluated in the region of the left ventricle. A receiver operating characteristic analysis was performed on both sets of data and the human and statistical decisions compared. For phase images, circular SD was shown to discriminate better between normal and abnormal than experienced observers, but no single statistic discriminated as well as the human observer for amplitude images. PMID- 1936048 TI - Myocardial accumulation and clearance of technetium 99m teboroxime at 100%, 75%, 50% and zero coronary blood flow in dogs. AB - Sequential changes in the regional distribution of technetium 99m Teboroxime (SQ30217) were evaluated in nine dogs with graded coronary artery stenosis, occlusion and reperfusion of either the left anterior descending or left circumflex arteries. 99mTc-Teboroxime accumulation recorded by planar imaging was compared with directly measured coronary blood flow (Doppler) and regional myocardial perfusion (microspheres). Serial images were recorded beginning at the time of injection and continuing for the next 18 min. The data were summed from minutes 2-3, 3-6, 4-8 and 9-18 after injection for comparison with the other parameters. Myocardial clearance of Teboroxime was analysed at each level of blood flow. There was a linear relationship between the Teboroxime activity ratio (abnormal/normal) and coronary blood flow (r = 0.96) and regional myocardial perfusion (r = 0.99). Zones of diminished perfusion were least apparent in the summed images recorded during minutes 2-3. In later images, the lesions were well visualized. The myocardial clearance half-times at 100%, 75% and 50% flow were not significantly different, while clearance half-time at total occlusion was significantly (P less than 0.01) faster. In the 3-6, 4-8 and 9-18 minutes summed images, the Teboroxime activity ratio increased significantly (P less than 0.01) after reperfusion compared with total occlusion. PMID- 1936049 TI - Technetium-99m teboroxime scintigraphy. Clinical experience in patients referred for myocardial perfusion evaluation. AB - In order to evaluate the clinical value of a new myocardial perfusion tracer, a series of 30 patients (25 male, 5 female, mean age 56 years) referred for thallium 201 stress/redistribution scintigraphy has been studied using stress/rest (n = 7) or rest/stress (n = 23) protocols with technetium 99m teboroxime (Cardiotec SQUIBB). In all cases coronary artery disease was known or highly probable, with a history of myocardial infarction in 18 cases. Medical treatment was not discontinued at the time of stress testing, and coronary angiography was available in 27 patients. Exercise tests for both tracers were carried out on a bicycle ergometer during the same day, and the levels of exercise achieved for the 201Tl study were very similar to those achieved for 99mTc-teboroxime. Studies performed in three planar projections were evaluated using a model with four territories: septal and anterior assumed to correspond to the left anterior descending artery, lateral and latero-posterior (left circonflex), inferior and posterior (right coronary artery) and apex. Classification of results was: normal, ischaemic, infarcted and infarcted with ischaemia. On comparison with the 201Tl results, agreement was found in 86% (37/43) of normal regions and in 82% (63/77) of abnormal regions. Relative to documented coronary artery lesions (27 patients), sensitivity and specificity of 201Tl and 99mTc-teboroxime for exact correspondence between arteries and territories were respectively: 201Tl: sensitivity 64%, specificity 60%; 99mTc teboroxime: sensitivity 62%, specificity 77%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936050 TI - Radiation risk of tissue late effects, a net consequence of probabilities of various cellular responses. AB - Late effects from the exposure to low doses of ionizing radiation are hardly or not at all observed in man probably due to the low values of risk coefficients that preclude statistical analyses of data from populations that are exposed to doses less than 0.2 Gy. In order to arrive at an assessment of potential risk from radiation exposure in the low dose range, the microdosimetry approach is essential. In the low dose range, ionizing radiation generates particle tracks, mainly electrons, which are distributed rather heterogenously within the exposed tissue. Taking the individual cell as the elemental unit of life, observations and calculations of cellular responses to being hit by energy deposition events from low LET type are analysed. It emerges that besides the probability of a hit cell to sustain a detrimental effect with the consequence of malignant transformation there are probabilities of various adaptive responses that equip the hit cell with a benefit. On the one hand, an improvement of cellular radical detoxification was observed in mouse bone marrow cells; another adaptive response pertaining to improved DNA repair, was reported for human lymphocytes. The improved radical detoxification in mouse bone marrow cells lasts for a period of 5-10 hours and improved DNA repair in human lymphocytes was seen for some 60 hours following acute irradiation. It is speculated that improved radical detoxification and improved DNA repair may reduce the probability of spontaneous carcinogenesis. Thus it is proposed to weigh the probability of detriment for a hit cell within a multicellular system against the probability of benefit through adaptive responses in other hit cells in the same system per radiation exposure. In doing this, the net effect of low doses of low LET radiation in tissue with individual cells being hit by energy deposition events could be zero or even beneficial. Since there was no simple additivity of equal effects from repeated exposures to equal doses and because of the potential effect of adaptive cell responses on the spontaneous evolution of malignancy in tissue, the extrapolation of risk with absorbed dose reaching down to zero, does not appear to be generally valid. PMID- 1936051 TI - Registration and display of the combined bone scan and radiograph in the diagnosis and management of wrist injuries. AB - A system has been developed for the registration and combined display of the X ray image and isotope bone scan. This system has been evaluated by prospectively studying 23 patients who were referred for suspected injury of the wrist. The registration system has an inherent precision for registration of about 1 mm. When patient positioning errors are included, this increases to about 4 mm. Two observers evaluated the sets of images prior to registration and after registration and combined display. They judged that in 16 out of 17 cases judged abnormal (observer 1) and 12 out of 18 cases judged abnormal (observer 2), the registration technique improved localization of a lesion. One case was rejected as registration was not possible due to incorrect positioning of the hand. PMID- 1936053 TI - Iodine 131 uptake in a pleuropericardial cyst: case report of a false-positive radioiodine total body scan result in a patient with a thyroid cancer. PMID- 1936052 TI - The clinician and the thyroid. AB - The goiter prevalence in iodine-deficient regions is up to 25%-54%. The most frequent disease in these endemic areas is non-toxic goiter, which is, however, oftentimes connected with autonomously functioning thyroid tissue leading to borderline or overt hyperthyroidism. Other thyroid diseases like cancer, thyroiditis and hypothyroidism play only a minor role in a thyroid clinic, while cases of Graves' disease may be observed more frequently. The most cost-effective tools to evaluate thyroid patients are the hand, ear and mouth of the thyroid clinician. The differential diagnosis of thyroid disorders may be evaluated by a battery of diagnostic tools like in-vitro tests and high performance imaging modalities. Once the diagnosis is established, the appropriate therapeutic procedures (drugs, radioiodine, surgery) have to be chosen. This review should be considered as a guideline for the diagnosis and treatment of thyroid diseases. In addition, special problems concerning elderly patients and pregnant women are discussed, including the differential diagnosis of thyroid diseases. PMID- 1936054 TI - Nuclear medicine prominent in American College of Cardiology meeting. AB - Approximately 5% of 1500 original scientific presentations directly addressed nuclear medicine topics with prominent emphasis on pharmacological stress testing, myocardial viability studies and evaluation of newer technetium-based imaging agents. In addition, a mini-course and two evening 'fireside' panel discussions were entirely devoted to discussions on the newer nuclear imaging techniques underlining the relative importance of scintigraphy in investigative cardiology. PMID- 1936055 TI - Variability of gastric emptying. PMID- 1936056 TI - Effects of cimetidine on drug metabolism in rat pups. AB - The effects of cimetidine on drug metabolism were studied in male and female rat pups and compared to similar effects in adult rats. As in adult rats, cimetidine 50 mg/kg/day i.p. for 7 days in the 2nd, 3rd, 4th or 5th weeks of life resulted in prolonged pentobarbitone sleeping times (diminished pentobarbitone hydroxylase activities), particularly when administered during the 3rd week. These effects of cimetidine were reversible since they continued only up to 2 weeks in males and 4 weeks in females, but by the 6th week were no longer observed. Pretreatment with cimetidine 15, 25 and 50 mg/kg/day i.p. for 7 days, resulted in a dose-dependent inhibition of aminopyrine N-demethylase and aniline hydroxylase as well as a prolongation of pentobarbitone sleeping time in both pups and adults, aniline hydroxylase being the least affected. In general, female pups were more adversely affected than male pups and adults. The therapeutic and toxicological relevance of these results in man are discussed. PMID- 1936057 TI - Tissue distribution of propafenone in the rat after intravenous administration. AB - Tissue distribution of propafenone has been studied in the rat. Measurement of propafenone was made in several tissues: plasma, heart, kidney, lung, liver, muscle, fat and brain, after i.v. administration of 2 mg/kg of the drug. The plasma propafenone kinetics profile can be described by a two-compartmental model. The pharmacokinetic parameters, derived from plasma levels, showed a t1/2 beta of 55.4 min, the central Vd/kg of 2.4 ml/kg, the Cl of 62.8 ml/min.kg and the AUC0-oo of 31.6 micrograms.min/ml. The analysis of the propafenone tissue distribution showed the highest concentration of drug in the lung, followed by the heart and kidneys. A significant concentration was found in brain, muscle and adipose tissue, with concentration ratios (tissue/plasma) above 1. The half-life values obtained for individual organs and tissues are similar to those obtained in plasma, around 1 h. In the post-distributive phase, plasma and tissue concentrations decline in parallel. PMID- 1936058 TI - Pharmacokinetics of pirprofen in children with juvenile chronic arthritis. AB - Pirprofen (100 or 200 mg; Rengasil) was administered to experimental groups of children (children with juvenile chronic arthritis, JCA) and to a control group of children (children without JCA) as a single dose or as repeated doses. The pharmacokinetics of pirprofen in these children were compared to the pharmacokinetic parameter values obtained in healthy volunteers and in elderly arthritic adults receiving 400 mg of pirprofen. The children were examined regularly and laboratory values were determined in order to detect possible side effects. The results demonstrated that the pharmacokinetics of pirprofen were similar for children and adults when taking into account the dose and the body weight. There was no drug accumulation after repeated administration of pirprofen. As already observed in rheumatic adults, pirprofen remains in synovial fluid longer than in plasma. PMID- 1936059 TI - Radiorespirometric patterns of [14C]-substrates in rats. II. Differences with the nature and administration route of the injection fluid. AB - The effects on the 14CO2 expiratory patterns of the nature and administration route of the injection fluid containing [14C]-glucose were studied. In the case of rapid intravenous injection, no difference in the radiorespirometric pattern was found with different glucose concentrations and volumes of the aqueous injection fluid. With intravenous injection, lower P1 heights and longer plateaus were recorded with the [14C]-glucose blood mixture as compared to the aqueous injection fluid. This result indicates that [14C]-glucose in the aqueous fluid injected into the blood vessel could be supplied into organs or tissues before mixing with the blood fluid in the blood vessel system. It is also suggested that larger amounts of [14C]-glucose are taken up into organs and tissues when the label was in aqueous solution rather than blood. In the case of intraduodenal infusion, a trace of glucose in a small volume (0.05 ml) of aqueous solution gave a similar radiorespirometric pattern to that given by intravenous injection of aqueous fluid. This indicates that there was fast absorption of glucose by the intestinal mucosa, which was not rate-limiting. A relatively large volume and very high concentration of glucose in the infusion fluid caused suppression of the radiorespirometric pattern. This may reflect physical suppression of intestinal peristalsis. PMID- 1936060 TI - Chlormezanone plasma and blood levels in patients after single and repeated oral doses and after suicidal drug overdose. AB - Chlormezanone plasma concentrations were determined in 5 volunteers (group 1) after a single oral dose of 200 mg of chlormezanone with high performance liquid chromatography. A plasma elimination half-life of 23 +/- 2.3 h was calculated. The mean peak chlormezanone plasma level was 1.86 +/- 0.2 micrograms/ml, 1 h after ingestion. Additionally, chlormezanone plasma levels were determined after repeated oral doses of chlormezanone recommended for treatment of muscular spasms due to degenerative skeletal disease. After 5 days of repeated daily doses of 3 x 200 mg (group 2; 12 patients) or 3 x 400 mg (group 3; 10 patients) of chlormezanone, mean predose chlormezanone plasma levels were 12.0 +/- 2.0 micrograms/ml (group 2) and 22.7 +/- 4.0 micrograms/ml (group 3), respectively. Comparable plasma concentrations were determined after 10 days of repeated doses of 3 x 200 mg or 3 x 400 mg of chlormezanone in 3 patients from each of these 2 groups. In 7 patients of group 3, chlormezanone had to be discontinued on the 5th day due to increasing muscular weakness, ataxia and exercise-inducible tachycardia. After a loading dose of 800 mg and repeated doses of 3 x 200 mg chlormezanone to 5 patients (group 4), plasma levels of 6.5 +/- 2.1 micrograms/ml, 8.9 +/- 2.2 micrograms/ml, 12.7 +/- 2.0 micrograms/ml, and 10.4 +/ 2.4 micrograms/ml were determined after 2, 8, 16, and 36 h, respectively. Trace amounts of a degradation product of the acid-labile chlormezanone could be detected in plasma besides the unchanged drug after administration of repeated oral doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936061 TI - Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery. AB - Limited information is available on the pharmacokinetics and tissue penetration of cefazolin in pediatric patients. Nine children (age 0.8-10 years) undergoing gastrointestinal operations were studied. A single dose of cefazolin, 15-26 mg/kg was given i.v. over 2-3 min at the time of induction of anaesthesia. Multiple (5 8) blood samples were collected during the operative procedure and in the recovery room. Tissue samples from the rectus abdominis muscle were obtained at the time of incision, during surgery, and at closure. The concentration of cefazolin was measured by a high performance liquid chromatographic method. Peak serum concentrations of cefazolin ranged from 85.8-269.4 mcg/ml. Serum and tissue concentrations at incision were 50.5-169.9 mcg/ml and 1.8-29.7 mcg/g; at closure the serum and tissue concentrations ranged from 17.3-60.9 mcg/ml and 1.19-29.70 mcg/g, respectively. Total clearance, apparent distribution volume, and elimination half-life of cefazolin were 1.43 +/- 0.54 ml/min/kg, 0.08 +/- 0.03 l/kg, and 1.68 +/- 0.55 h respectively. Tissue concentrations of cefazolin were maintained above its minimum inhibitory concentrations against common susceptible pathogens. Hence, the current dosing regimen of cefazolin is adequate to protect against infection in pediatric patients undergoing gastrointestinal surgery. PMID- 1936062 TI - Propranolol does not alter flutoprazepam kinetics and metabolism in the rat. AB - The influence of propranolol on the disposition of flutoprazepam, a benzodiazepine derivative extensively biotransformed by hepatic microsomal oxidation, was evaluated in the rat. Propranolol was infused subcutaneously with osmotic minipumps (5 mg/day) to obtain steady-state concentrations of about 200 ng/ml. Flutoprazepam (5 mg/kg) was given intraperitoneally on the third day of propranolol infusion. There was some variability in flutoprazepam disposition, consistent with the concept of an extensive first-pass metabolism of high extraction drugs. Propranolol had no significant effects on the kinetics of flutoprazepam or norflutoprazepam, an active metabolite possibly accounting for a substantial part of the parent compound's pharmacological and clinical effects. It was concluded that there is no evidence of any pharmacokinetic interaction between this beta-adrenoceptor blocker and flutoprazepam in the rat. PMID- 1936063 TI - Effects of endurance training and exercise on tissue antioxidative capacity and acetaminophen detoxification. AB - Both acute acetaminophen toxicity and physical exercise are accompanied by structural and functional damage to tissues. For acute acetaminophen toxicity, this damage occurs mainly in the liver. This damage, which is believed to be initially caused by oxidation and/or arylation, occurs only after depletion of liver glutathione (GSH). GSH normally protects against oxidation and/or arylation. Prolonged physical exercise also depletes GSH in the body. We hypothesized that with endurance training (repeated oxidant stress) tissues will develop mechanisms to prevent GSH depletion. Our results show that, for the same amount of submaximal exercise, trained rats are able to maintain their levels of GSH or their GSH redox status (in the liver, heart, skeletal muscle and plasma) in contrast to their untrained counterparts. Also, upon administration of acetaminophen, trained rats show a less pronounced depletion in liver GSH than untrained rats. We also hypothesized that training may lead to improved maintenance of tissue GSH homeostasis because of induction in the enzyme pathways of protection. We observe that training significantly increases (50-70%) glutathione peroxidase and reductase, glucose-6-phosphate dehydrogenase, and catalase activity in heart and skeletal muscle. Since GSH, in addition to providing cellular protection, also functions in other physiological processes including transport and metabolism, the training-induced benefits seen here may have more far-reaching consequences than ever before realized. PMID- 1936064 TI - Pharmacokinetics and metabolism of diltiazem in rabbits after a single intravenous or single oral administration. AB - Diltiazem (DTZ) 5 mg/kg was given to rabbits either orally (n = 5) or intravenously (n = 6). Plasma concentrations and urinary excretion of DTZ and its metabolites were determined by a high performance liquid chromatography assay (HPLC) for 12 and 48 h post dose, respectively. The results showed that the metabolism and disposition of DTZ in rabbits was similar to that of humans, mean absolute bioavailability (F) of DTZ was approximately 30% and the systemic clearance was 64.0 ml/min/kg. The metabolism of DTZ between the two routes of administration was quantitatively different in that higher plasma concentrations of the metabolites were observed after the intravenous dose. This could be a result of incomplete oral absorption, higher clearance of DTZ and the metabolites during the first pass through the liver (i.e. higher sequential first pass effect), and/or extrahepatic metabolism. On the basis of the plasma concentration time profiles and urinary excretion of DTZ and its metabolites, it is concluded that the rabbit is a suitable animal model to investigate the kinetics and metabolism of DTZ. PMID- 1936065 TI - Diltiazem pharmacokinetics in elderly volunteers after single and multiple doses. AB - In young healthy volunteers diltiazem does not have linear kinetics between single and multiple doses. Elimination half-life increases and gives AUC's and Cmax higher than those predicted from single dose data. Kinetics of diltiazem were assessed in 16 healthy elderly after a single 60 mg dose and in 24 healthy elderly after 60 mg every 8 h for 7 days. Thirteen participants completed both studies. Elimination half-life, AUC0-24, AUC0-infinity, and Cmax were (mean +/- SE) 7.4 (1.2) h, 349 (34) ng/ml.h, 392 (44) ng/ml.h, and 43 (5) ng/ml respectively after a single dose. After multiple doses elimination half-life, AUC0-48, AUC0-infinity, Cmax and Cmin were respectively 5.7 (0.3) h, 974 (107) ng/ml.h, 1022 (108) ng/ml.h, 102 (7) ng/ml and 43 (5) ng/ml. Exploratory statistics on the 13 volunteers common to both studies showed that the ratio of AUC desacetyl-diltiazem (DAD)/AUC diltiazem rose between single and multiple doses while elimination half-life of both diltiazem and N-desmethyl-diltiazem (MA), tmax, and AUC MA/AUC diltiazem were not affected. The conclusion of this study is that elimination half-life of diltiazem does not increase in elderly between single and multiple doses, possibly due to an increased biotransformation into DAD. PMID- 1936066 TI - Comparative pharmacokinetics and pharmacodynamics of eterobarbital and phenobarbital in normal volunteers. AB - The comparative pharmacokinetics and pharmacodynamics of single oral doses of eterobarbital (N,N'-dimethoxymethylphenobarbital, DMMP, 400 mg) and phenobarbital (200 mg) were evaluated in a double-blind study in 8 normal volunteers. Following administration of DMMP, no unchanged drug could be detected in serum. The active monomethoxymethyl metabolite (MMP) appeared rapidly in the circulation but its concentration remained generally low and declined below the limit of detection (0.5 micrograms/ml) usually before 9.5 h. Serum levels of DMMP-derived PB increased slowly and reached a peak between 24 and 48 h in most cases. One subject showed an atypical pharmacokinetic profile, characterized by relatively high levels of MMP and a delayed appearance of low levels of PB. After administration of PB, serum drug levels peaked within 1.5 h and remained, at all sampling times, higher than those observed after intake of DMMP. Compared with DMMP, PB induced greater sedative effects as assessed by visual analogue rating scale, critical flicker fusion frequency and multiple sleep latency tests. PMID- 1936067 TI - Effect of the position of the cyano-group of cyanopregnenolones on their drug metabolic inducing activity. AB - The effect of the position of the cyano-group of several cyanopregnenolones on the body's resistance to drugs and on drug metabolism was investigated. Female rats were pretreated with 2 alpha-, 6-, 16 alpha-, 17 alpha-cyano- or 16 alpha cyanomethyl-pregnenolone or with pregnenolone, and the (in vivo) resistance to zoxazolamine, digitoxin and indomethacin, as well as the in vitro drug metabolism (post mitochondrial fraction) of zoxazolamine and ethylmorphine were determined. It was found that the 16-derivative was the most active in this respect, the 2- and 17-cyanopregnenolones were less active but significantly potent compared to controls, while the 6-cyano, the 16-cyanomethyl derivatives and pregnenolone were essentially inactive. These differences were explained in terms of an effective or poor fit of the steroids to their receptor. The poor performance of pregnenolone-16 alpha-acetonitrile was attributed to electronic effects. A hypothesis of some structural features of the receptor site for its interaction with the cyanopregnenolone inducers was presented. PMID- 1936068 TI - Induction of cytochrome P-450 isozymes upon repeated administration of nifedipine. AB - In experiments on male Wistar rats it has been found that nifedipine administration at a dose of 10 mg/kg body weight i.p. daily for 20 days did not significantly increase the total amount of cytochrome P-450 but markedly increased the 7 alpha-, 16 beta- and 6 beta-hydroxylation of androstenedione in liver microsomes, suggesting the induction of cytochromes P-450IIA1, P-450IIB1, and P-450IIIA1, respectively. The induction of cytochrome P-450IIIB1 was also confirmed immunochemically with polyclonal antibodies against cytochrome P 450IIB1/B2. PMID- 1936069 TI - New data on the pharmacokinetics of adriamycin and its major metabolite, adriamycinol. AB - Twenty-two days after administration by intravenous bolus, of 50 mg of adriamycin to several patients we found concentrations of adriamycin and adriamycinol of the order of 100 pcg/ml. In theory, however, with a terminal half-life of 30 h, the plasma levels of adriamycin and adriamycinol should be close to 0.1 pcg/ml. Further pharmacokinetic investigation was therefore necessary. We have retained for this study nine male patients, aged between 53 and 69 years who received 25 to 50 mg of adriamycin by slow intravenous injection. The HPLC method permitted the detection of 50 pcg/ml of adriamycin and adriamycinol, with the possibility of monitoring their elimination during 120 h (and in one case during 160 h). The terminal half-lives of elimination estimated in 8 patients were respectively 110 +/- 52 h for adriamycin and 92 h 50 min +/- 43 h for adriamycinol. Surface ratios under adriamycinol curves against calculated adriamycin was 1.10 +/- 0.26. Plasma levels found during the To in certain patients correspond to the end of the drug elimination of the previous treatment. It is difficult with a half-life to 110 h to predict the effects of residual concentrations of adriamycin and adriamycinol. PMID- 1936070 TI - The metabolic fate of the anti-parkinsonian drug budipine in rats. AB - The metabolic fate of the anti-Parkinsonian drug budipine was studied in rats after oral administration. The presence of an aromatic hydroxylation product, metabolite M1, and its O-sulphate conjugate was confirmed. Three new minor metabolites, budipine N-oxide, metabolite M1 N-oxide and a secondary metabolite derived from M1 via hydroxylation of a methyl of the tert-butyl group, were isolated and identified in rat urine. The presence of a metabolite M1-glucuronic acid conjugate, was also established through different enzymatic treatments of the rat urine. PMID- 1936071 TI - Pharmacokinetics of daunorubicin and daunorubicinol in plasma, P388 and B16 tumours. Comparison with in vitro cytotoxicity data. AB - The comparison of pharmacokinetics of DNR in mouse plasma, in the DNR naturally resistant B16 melanoma and in the DNR naturally sensitive P388 leukemia showed that there is no direct correlation between total concentrations of this drug in tumours and the sensitivity resistance of these tissues. A finding which demonstrates the inadequacy of distribution models to select new potential anticancer drugs. Cytotoxicity of DNR and its metabolites to B16 melanoma and P388 leukemia cell lines were determined in vitro. Calculated inhibitory concentrations 50 (IC50) were compared to maximal concentrations determined by pharmacokinetic studies. In all cases in vitro IC50 were lower than Cmax values. Moreover, resistant cells in vivo were found to be sensitive to DNR and metabolites when they are propagated in vitro. Tissue concentrations, as well as in vitro data, were fitted to appropriate models by an original program (FADHA) which uses the simplex method to minimize a non-linear cost function. Best fit models were chosen by statistical criteria. PMID- 1936073 TI - Pharmacokinetics of rokitamycin after single administration to healthy volunteers. AB - The pharmacokinetics of rokitamycin tablets were studied in 12 healthy volunteers in a randomized cross-over design. The doses tested were 200 mg, 300 mg, 400 mg and 600 mg, as single oral administration. Rokitamycin was absorbed quickly with Tmax for all doses around 30 min after drug intake. Total AUC and Cmax values were linearly related to the administered dose. The buffer formulation determined a low interindividual variation. The overall findings show a good similarity with the data obtained in Japanese subjects. Tolerability was very good. PMID- 1936072 TI - Metabolism of anti-herpes agent 5-(2-chloroethyl)-2'-deoxyuridine in mice and rats. AB - The enzymatic splitting and metabolic elimination of anti-viral agent 5-(2 chloroethyl)-2'-deoxyuridine [CEDU] have been studied. For elucidation of structures of metabolites, several different kinds of extraction, purification and spectroscopic methods were used (Extrelut LC, TLC, HPLC, MS, NMR, IR, UV and CD). For mass spectral analysis, various ionization techniques (EI, CI and FAB MS) were performed as complementary methods. After oral administration of [14C] CEDU to mice and rats, the parent compound, 5-(2chloroethyl) uracil [CEU] and hydroxylated CEU metabolites were isolated and identified from urine and faeces by the above mentioned methods. The CEDU showed rapid phosphorolysis in vitro with thymidine phosphorylase Km 41.0 +/- 5.0; and uridine phosphorylase Km 10.0 +/- 1.5. The cleavage of the N-glycosidic bond of the nucleoside analogue and a new metabolic pathway of CEDU [stereoselective oxidation of 5-(2-chloroethyl) uracil] was observed in both species. PMID- 1936074 TI - Absolute bioavailability of moxonidine. AB - In a randomized 2-way cross-over study with eighteen healthy male volunteers, two moxonidine preparations (tablets, treatment A vs. intravenous solution, treatment B) were tested to investigate absolute bioavailability and pharmacokinetics of moxonidine. The preparations were administered as single doses of 0.2 mg; prior to and up to 24 h after administration blood samples were collected and the plasma moxonidine concentrations determined. Urine samples were collected prior to and at scheduled intervals up to 24 h after administration for the determination of unchanged moxonidine. Moxonidine plasma and urine concentrations were determined by a validated gas chromatographic/mass spectrometric method with negative ion chemical ionization. The mean areas under the plasma concentration/time curves were calculated as [mean +/- standard deviation] 3438 +/- 962 pg.h/ml (AUC(0----Tlast)) and 3674 +/- 1009 pg.h/ml (AUC(0----infinity)) for treatment A; 3855 +/- 1157 pg.h/ml (AUC(0----Tlast)) and 4198 +/- 1205 pg.h/ml (AUC(0----infinity)) for treatment B. Mean peak plasma concentrations of 1495 +/- 646 pg/ml were attained at 0.56 +/- 0.28 h after oral treatment, mean peak plasma concentrations after intravenous treatment reached 3965 +/- 1342 pg/ml at 0.17 +/- 0.01 h (= coinciding with end of infusion). The mean terminal half-lives of moxonidine were derived as 1.98 h after administration of the tablet and as 2.18 h after infusion. The amounts of moxonidine excreted in urine during the 24 h following administration (Ae(24h)) in absolute figures and as percentage of the dose administered were 102 +/- 26 micrograms or 51 +/- 13% for the tablet and 122 +/- 33 micrograms or 61 +/- 16% for the infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936075 TI - N-dephenylated and N-phenyl urinary metabolites of mociprazine (CERM 3517) in beagle dogs after oral administration. A mass spectrometric determination. AB - CERM 3517 (mociprazine), a new anti-emetic compound, was administered orally to six beagle dogs at 10 mg/kg b.i.d. for four days. Unconjugated urinary metabolites were identified by GC-MS analysis against synthesized reference compounds, after solvent extraction, purification by TLC and concentration. Twenty one metabolites were identified indicating the following biotransformations: N-dephenylation followed by reactions on the exposed secondary amine such as methylation acetylation; and parahydroxylation on the phenyl ring, and monohyrdoxylation on the cyclohexyl ring in different positions. The parahydroxylation on the phenyl ring was confirmed by NMR analysis. Some reactions on the secondary amine were unexpected, such as N-formylation. N dephenylation and N-formylation were confirmed not to be artifacts. The role of the para-hydroxyl intermediate was proved to be essential for the N-dephenylation after intravenous administration of meta- and para-hydroxylated derivatives of CERM 3517 to five beagle dogs. PMID- 1936076 TI - Diltiazem pharmacokinetics in elderly volunteers after single and multiple doses. AB - In young healthy volunteers diltiazem does not have linear kinetics between single and multiple doses. Elimination half-life increases and gives AUC's and Cmax higher than those predicted from single dose data. Kinetics of diltiazem were assessed in 16 healthy elderly after a single 60 mg dose and in 24 healthy elderly after 60 mg every 8 h for 7 days. Thirteen participants completed both studies. Elimination half-life, AUC0-24, AUC0-infinity, and Cmax were (mean +/- SE) 7.4 (1.2) h, 349 (34) ng/ml.h, 392 (44) ng/ml.h, and 43 (5) ng/ml respectively after a single dose. After multiple doses elimination half-life, AUC0-48, AUC0-infinity, Cmax and Cmin were respectively 5.7 (0.3) h, 974 (107) ng/ml.h, 1022 (108) ng/ml.h, 102 (7) ng/ml and 43 (5) ng/ml. Exploratory statistics on the 13 volunteers common to both studies showed that the ratio of AUC desacetyl-diltiazem (DAD)/AUC diltiazem rose between single and multiple doses while elimination half-life of both diltiazem and N-desmethyl-diltiazem (MA), tmax, and AUC MA/AUC diltiazem were not affected. The conclusion of this study is that elimination half-life of diltiazem does not increase in elderly between single and multiple doses, possibly due to an increased biotransformation into DAD. PMID- 1936078 TI - Effect of fecal loading with/without peritonitis on the healing of a colonic anastomosis: an experimental study. AB - An experimental randomized prospective study was carried out in 64 dogs to evaluate the effect of intraluminal fecal matter at the anastomosis with/without peritonitis on the healing of a colonic anastomosis. The animals, none of whom had bowel preparation, were randomized in four groups: group I sigmoid resection and anastomosis, group II sigmoid resection and intraluminal fecal diversion from the anastomosis, group III induced fecal peritonitis, sigmoid resection and anastomosis and group IV induced fecal peritonitis, sigmoid resection and intraluminal fecal diversion from the anastomosis. Forty-eight hours before sacrifice at 5, 10 and 15 days, 10 microCi/kg C14 proline was given intravenously. Specimens were analyzed for hydroxyproline content, tissue counts and specific activity. The tissue counts and specific activity were analyzed by three-way analysis of variance. Overall, regardless of the groups, there was a statistically significant decrease in specific activity and tissue count from day 5 to day 15 and day 10 to day 15 at the anastomosis (p less than 0.05). When comparing groups II and IV to groups I and III, there was a significant increase in specific activity and tissue count at the anastomosis of group II and IV (p less than 0.05). This experimental study demonstrates that early anastomotic healing can occur even in presence of treated peritonitis as long as the fecal matter is diverted and prevented from coming in contact with the anastomotic site without disrupting the bowel continuity or function. PMID- 1936077 TI - Investigations on the in vitro metabolism of five synthetic 19-norprogestins using hepatocyte suspensions isolated from five laboratory animal species. AB - Five synthetic progestins of the 19-nortestosterone type (norethisterone, NET; levonorgestrel, LN; gestodene, GEST; NET-3-oxime, NETO; norgestimate, NGM) were investigated in the in vitro hepatocyte model. Radiolabelled progestins were added to hepatocyte suspensions (3 x 10(6) cells/ml) freshly prepared from female rat, guinea pig, rabbit, dog (beagle) and cynomolgus monkey. Drug level decreases (NET, LN, GEST) and prodrug conversions (NETO, NGM) were followed by radiochromatography (HPLC) for 60 min. In the case of NET and NETO the conversion into ethinyl estradiol (EE2) was quantified by RIA after HPLC separation. Half lives of drug level decreases (t1/2), areas under the curves (AUC) and metabolic clearance rates (MCR) were estimated for all progestins. For NETO and NGM the percentages of conversion into NET and LN were calculated, respectively, and levels of EE2 determined in the case of NET and NETO. Rat hepatocytes showed an extremely high metabolic activity towards NET, LN and GEST resulting in t1/2 values of below 2 min. Respective values for rabbit hepatocytes ranged from 5-8 min, whereas half-lives calculated for liver cells from guinea pig, dog and monkey were generally above 30 min. A drastic increase in t1/2 was found for NETO (as compared to NET) in hepatocytes from rat, rabbit and monkey but not from guinea pig. Dog hepatocytes degraded NETO about 3 times more rapidly than NET. NGM was degraded much faster than LN in hepatocytes from all species except the rat. Liver cells from guinea pig and dog seem to be able to metabolize the 3 oxime group much more rapidly than hepatocytes from the other animal species. The lowest degree of prodrug conversion of 4% was observed for NGM and dog hepatocytes. Elevated EE2 levels were found in all experiments with NET and NETO. Results of NET, LN and GEST were compared with published in vivo experiments. No correlations were found for t1/2, MCR, and AUC. PMID- 1936079 TI - What happens to the rectal muscular cuff? An experimental study in dogs. AB - The anatomy and histology of the rectal muscular cuff was studied in 15 dogs with an ileal pouch-anal anastomosis. Eight channel, three-dimensional anal manometry showed normal maximal squeeze pressure (128 +/- 20 mm Hg) compared to a control group (135 +/- 4 mm Hg). The rectal muscular cuff showed complete absence of the cuff in three cases. In 12 dogs, the rectal cuff was retracted to a length of less than 1 cm, the muscle fibers were degenerated and fibrotic. The results in the canine model and the clinical results of patients with an ileal pouch-anal anastomosis with a cuff demonstrated that a rectal muscular cuff is not essential to maintain continence after ileal pouch-anal anastomosis. PMID- 1936080 TI - Long-term toxicity of preoperative 4'-epidoxorubicin (Epi-adriamycin) in partially hepatectomized rats. AB - 4'-Epidoxorubicin (Epi-A) administered immediately prior to liver resection has been suggested as treatment for patients with primary liver carcinoma. Long-term toxicity was studied in rats given a single dose of Epi-A intravenously immediately prior to a standard partial hepatectomy (PH). After 52 weeks only 9% of the rats given 5 mg/kg + PH were alive, 79% of the rats given 2 mg/kg + PH and 92% of the PH control survived. The weight gain of the rats given 5 mg/kg + PH was only 17% of that of PH controls. Signs of congestive heart failure were observed in some rats while in others moderate kidney lesions. No histopathological lesions were detected by light microscopy in heart, liver, spleen and bone marrow. For the rats given 2 mg/kg + PH body weight gain, microscopic observations and blood chemistry data (total protein, albumin, alkaline phosphatase, alanine aminotransferase, total bilirubin, creatinine and urea) were comparable to the PH controls. No significant differences in survival were registered between partially hepatectomized and sham-operated rats. The results indicate that Epi-A may be given preoperatively to liver resection without inducing long-term effects on vital organs. PMID- 1936081 TI - Pancreatic cationic elastase in porcine experimental pancreatitis. AB - A radioimmunoassay for porcine, cationic, pancreatic elastase (irPE) is described. Normal porcine serum contains only small amounts of irPE (less than 3 micrograms/l). IrPE in serum and peritoneal exudate from 6 pigs with experimental pancreatitis was found mainly in a molecular form corresponding to free pro enzyme. The presence of alpha 1-, alpha 2-macroglobulin-bound elastase-like enzymatic activity in the peritoneal exudates from pigs with pancreatitis, however, indicates that the proteinase is to some extent released as the active enzyme. In some pigs with pancreatitis, the elastase-like activity against Succ(Ala) in the peritoneal exudates increased during the experiment, arguing for a progressive activation of pro-elastase. Free proteolytic activity was not observed in any of the peritoneal exudates. This low degree of activation of elastase and the fact that the elastase inhibiting capacity is substantially larger than the trypsin inhibiting capacity in serum and biological fluids, leads us to the conclusion that active elastase is not a factor of principal importance in the pathogenesis of proteinase inhibitor consumption and tissue damage in our experimental pancreatitis model. PMID- 1936082 TI - Redistribution of intraorgan blood flow in acute, hyperdynamic porcine endotoxemia. AB - In a standardized porcine model of acute, hyperdynamic endotoxemia the distribution of intraorgan blood flow within heart, kidney and brain was analyzed. Twelve pigs received either short-term (23 min) or long-term (205 min) continuous intravenous infusion of endotoxin (Salmonella abortus equi). A high cardiac output/low peripheral resistance state was maintained throughout the 3.5 h observation period. Total organ blood flow in heart, kidney and brain remained high; however, already small amounts of endotoxin provoked a significant redistribution of intraorgan blood flow within the left ventricle and the kidney. These characteristic alterations were absent in a control group of 5 animals subjected to the same protocol, but receiving 0.9% saline instead of endotoxin. Deterioration of respiratory function developed exclusively after continuous intravenous endotoxin infusion over 205 min, indicating incipient organ failure. Using electron microscopy, endothelial cells swelling and entrapment of blood cells in capillaries of the midmyocardium as well as severe ultrastructural damage in the kidney could be demonstrated already after 90 min of endotoxemia in two additional animals. It is concluded that already in the initial phase of acute endotoxemia, in the presence of high cardiac output and high global organ blood flow microcirculatory deterioration and organ failure develops. As small amounts of endotoxin are capable of inducing these alterations, earliest possible diagnosis of endotoxemia should be achieved in critically ill patients. PMID- 1936083 TI - Carbohydrate ingestion during prolonged exercise: effects on metabolism and performance. AB - It is well recognized that energy from CHO oxidation is required to perform prolonged strenuous (greater than 60% VO2 max) exercise. During the past 25 years, the concept has developed that muscle glycogen is the predominant source of CHO energy for strenuous exercise; as a result, the potential energy contribution of blood glucose has been somewhat overlooked. Although during the first hour of exercise at 70-75% VO2max, most of the CHO energy is derived from muscle glycogen, it is clear that the contribution of muscle glycogen decreases over time as muscle glycogen stores become depleted, and that blood glucose uptake and oxidation increase progressively to maintain CHO oxidation (Fig. 1.7). We theorize that over the course of several hours of strenuous exercise (i.e., 3 4 h), blood glucose and muscle glycogen contribute equal amounts of CHO energy, making blood glucose at least as important as muscle glycogen as a CHO source. During the latter stages of exercise, blood glucose can potentially provide all of the CHO energy needed to support exercise at 70-75% VO2max if blood glucose availability is maintained. During prolonged exercise in the fasted state, however, blood glucose concentration often decreases owing to depletion of liver glycogen stores. This relative hypoglycemia, although only occasionally severe enough to result in fatigue from neuroglucopenia, causes fatigue by limiting blood glucose (and therefore total CHO) oxidation. The primary purpose of CHO ingestion during continuous strenuous exercise is to maintain blood glucose concentration and thus CHO oxidation and exercise tolerance during the latter stages of prolonged exercise. CHO feeding throughout continuous exercise does not alter muscle glycogen use. It appears that blood glucose must be supplemented at a rate of approximately 1 g/min late in exercise. Feeding sufficient amounts of CHO 30 minutes before fatigue is as effective as ingesting CHO throughout exercise in maintaining blood glucose availability and CHO oxidation late in exercise. Most persons should not wait, however, until they are fatigued before ingesting CHO, because it appears that glucose entry into the blood does not occur rapidly enough at this time. It also may be advantageous to ingest CHO throughout intermittent or low-intensity exercise rather than toward the end of exercise because of the potential for glycogen synthesis in resting muscle fibers. Finally, CHO ingestion during prolonged strenuous exercise delays by approximately 45 minutes but does not prevent fatigue, suggesting that factors other than CHO availability eventually cause fatigue. PMID- 1936084 TI - The biomechanics of cycling. PMID- 1936085 TI - Demand vs. capacity in the aging pulmonary system. PMID- 1936086 TI - Community intervention for promotion of physical activity and fitness. PMID- 1936087 TI - The annual survey of catastrophic football injuries: 1977-1988. PMID- 1936088 TI - The plasticity of skeletal muscle: effects of neuromuscular activity. PMID- 1936089 TI - Regulation of muscle sympathetic nerve activity during exercise in humans. AB - Recent investigations using direct (microneurographic) recordings of MSNA have provided a substantial amount of new information on the regulation of sympathetic nervous system control of nonactive skeletal muscle blood flow during exercise in humans. Some of the new conclusions from these studies discussed in this review include: 1. The direction, pattern and magnitude of the MSNA response to exercise depend on the collective influence of a number of factors, including the mode (isometric or rhythmic), intensity, and duration of the exercise, the size of the contracting muscle mass, and possibly the level of conditioning (physical training) of the exercising muscles. The MSNA response also appears to be tightly coupled with the onset and progression of muscle fatigue, at least during sustained, isometric contractions. 2. Increases in MSNA evoked during exercise with the arms are fairly uniform among different skeletal muscle nerves, and these responses correlate strongly with changes in venous plasma norepinephrine concentrations, limb vascular resistance and arterial blood pressure. Thus, increases in this neural activity during exercise are associated with the expected physiological responses. 3. The MSNA response to the same level of exercise varies markedly among healthy subjects but appears to be consistent over time within a particular subject. 4. The muscle metaboreflex (muscle chemoreflex) is the primary-mechanism by which MSNA is stimulated during small-muscle, isometric exercise in humans. In contrast, central command has a relatively weak influence on MSNA during this type of exercise. 5. Muscle metaboreflex stimulation of MSNA also occurs during dynamic exercise, but only at or above moderate, submaximal intensities (i.e., not during mild exercise). 6. Muscle metaboreflex-evoked increases in MSNA during exercise are strongly associated with glycogenolysis and the consequent cellular accumulation of hydrogen ions in the contracting muscles. 7. Sympathoinhibitory cardiopulmonary reflexes do not appear to modulate the MSNA responses to isometric exercise in the healthy human. However, arterial baroreflexes exert a potent inhibitory effect on MSNA during this form of exercise. The mechanisms involved in the regulation of MSNA during large-muscle, dynamic leg exercise is an important topic for future investigations, as is the relationship between MSNA and sympathetic outflow to other regional circulations (e.g., heart, viscera, skin) during various forms of exercise. PMID- 1936090 TI - Exercise, bone mineral density, and osteoporosis. PMID- 1936091 TI - Arm movements in three-dimensional space: computation, theory, and observation. PMID- 1936092 TI - Myotendinous junction injury in relation to junction structure and molecular composition. PMID- 1936093 TI - Exercise, training and hypertension: an update. PMID- 1936094 TI - Adenine nucleotide metabolism in contracting skeletal muscle. AB - During steady-state muscle contractions, ATP production and utilization are well matched. When the rate of ATP hydrolysis exceeds the capacity of a given muscle fiber to phosphorylate ADP, the ADPf and AMPf concentrations rise, first leading to the deamination of adenylates and subsequently to the dephosphorylation of AMP or IMP, or both, to their respective nucleosides and bases. Several proposed roles for the purine nucleotide cycle in skeletal muscle have been reviewed and evaluated. The deaminating limb of the purine nucleotide cycle is most important; it maintains the ATP/ADP ratio and lessens adenine nucleotide degradation. Regulation of glycolytic pathway enzymes by the products of AMP deamination (IMP and NH4+) does not seem likely. During reamination there is a net production of fumarate, with the branch-chain amino acids potentially supplying a significant fraction of the amine; reamination, however, is probably not concurrent with a high rate of deamination. Evidence from some studies of AMP deaminase-deficient persons suggests that an intact purine nucleotide cycle is required for normal muscle function during intense exercise; the issue is clouded, however, by the occurrence of asymptomatic AMP deaminase deficiency. Skeletal muscle is capable of extensive adenine nucleotide degradation during severe, energy-depleting conditions. Purine nucleosides and bases not reincorporated by the salvage pathway must be synthesized de novo. The capacity for de novo synthesis differs among fiber types, being highest in muscle with the highest oxidative capacity. PMID- 1936095 TI - Sport and collective violence. PMID- 1936097 TI - The measurement of dynamic latent variables in longitudinal aging research: quantifying adult development. AB - Dynamic latent variables involve systematic intraindividual change over time. Although it seems natural to apply traditional measurement theory to dynamic latent variables, in fact this is often inappropriate. Traditional measurement theory is based on the idea of static latent variables and offers little guidance to the researcher who wishes to measure a dynamic latent variable with a high degree of accuracy and validity. It is the contention of this article that measurement of a dynamic latent variable must start from a clearly defined substantive theory about human development. Two approaches that take this perspective are presented: the longitudinal Guttman simplex (LGS), a measurement model for dynamic latent variables undergoing irreversible cumulative, unitary development; and latent transition analysis (LTA), a more general latent class measurement model. PMID- 1936098 TI - Multi-modal selection effects in the study of adult development: a perspective on multivariate, replicated, single-subject, repeated measures designs. AB - Some of the selection issues that bear upon the conduct of research using multivariate, replicated, single-subject repeated measures designs are examined and their implications for the study of developmental phenomena discussed. The choices of participants, variables, occasions of measurement, etc., made in the conduct of empirical research all involve some kind of selection. These choices, therefore, introduce selection effects into collected data which, in turn, threaten the generalizability of one's conclusions. Data analyzed for single subjects, for example, are suspect regarding generalizability to other individuals. While the limits of generalizability to persons is a concern to be taken seriously, the concern properly applies to all modes of data classification. Discussions of the importance of person selection emphasize representative sampling (of persons) and generalization to populations of persons. Attention to the selection of variables has led to a focus on multivariate approaches to measurement. For the developmentalist, the occasions mode, which is either implicitly or explicitly involved in definitions of change, is especially relevant to concerns about generalizability. Whether one considers stability or change, the effects of temporal selection ought to be a central concern in designing research. PMID- 1936096 TI - The metabolic effects of exercise-induced muscle damage. AB - Exercise-induced skeletal muscle damage results in a remarkable number of localized and systemic changes, including release of intracellular proteins, delayed onset muscle soreness, the acute-phase response, and an increase in skeletal muscle protein turnover. These exercise-induced adaptations appear to be integral to the repair of the damaged muscle and may be essential for hypertrophy. Chronic exercise produces adaptations in skeletal muscle, resulting in increased capacity of oxidative metabolism; the repair of damaged muscle resulting in hypertrophy may be an important mechanism for protection against further exercise-induced damage. Although the release of CK from skeletal muscle following damage is a commonly observed phenomenon, circulating CK activity is not a quantitative and, in some cases, even a qualitative indicator of skeletal muscle damage. Eccentric exercise-induced skeletal muscle damage offers an opportunity to investigate the signals and modulators of the repair of muscle damage, a process that may be central to the adaptations in muscle as a result of chronic activity. PMID- 1936099 TI - Structural modeling of mixed longitudinal and cross-sectional data. AB - In this paper we describe some mathematical and statistical models for dealing with changes over age. We concentrate specifically on the use of a structural equation modeling (SEM) approach (using computer programs like LISREL) to deal with issues of: (1) group differences in regression parameters, (2) differences in longitudinal and cross-sectional results, (3) differences due to longitudinal attrition, and (4) mixtures of these problems. To illustrate these ideas we use data from a previous study of hypertension and intellectual abilities (from Schultz, Elias, Robbins, Streeten, and Blakeman, 1986). PMID- 1936100 TI - Quantitative topics in research on aging. AB - The origins of the present series of articles on quantitative topics in aging research are presented. Specific articles are described, the purposes and goals of the quantitative series are set forth, and the relationship of this body of knowledge to the scientific status of the area of aging research is discussed. PMID- 1936101 TI - Addendum to: studies of aging using defined rodents: a bibliography. PMID- 1936102 TI - An updated bibliography of the neurobehavioral aspects of diabetes mellitus. PMID- 1936103 TI - Statistical tools and status symbols. AB - This paper sets the stage for a series of edited papers which follow. It is argued that obvious statistical blunders (mortal sins) have not disappeared entirely from the aging literature, but that the most frequent error now is that of choosing a less powerful analytic solution when a more powerful (and equally applicable) one is at hand (a venial sin). Clearly, it is argued, power must be considered in relationship to the theoretical model, the condition of the data set, and the research question. Editors and reviewers, it is argued, must cut through the "glitter" of new fads and the security of tradition in order to objectively consider the merits of new statistical applications. More importantly, without knowledge of the issues, limitations, and advantages of contemporary and emerging analytic techniques, authors cannot make good analytic choices and defend them effectively. The time between presentation of innovative approaches in the quantitative journals and application in the aging literature contributes to traditionalism in data analysis. Overzealousness by advocates of new approaches often contributes to premature embracing of them. Thus the papers that follow were designed to bring new methods to the "working-researcher" with a frank appraisal of assumptions, proper and improper applications, and limitations. Authors of these papers were challenged to communicate in plain and understandable terms and to provide practical examples. PMID- 1936104 TI - The HELP-LDL-apheresis multicentre study, an angiographically assessed trial on the role of LDL-apheresis in the secondary prevention of coronary heart disease. I. Evaluation of safety and cholesterol-lowering effects during the first 12 months. HELP Study Group. AB - Fifty-one patients with coronary heart disease (CHD) and LDL-cholesterol levels greater than or equal to 200 mg dl-1 despite diet and drug therapy have been recruited into an angiographically controlled, multicentre, two-year study to evaluate HELP-LDL-apheresis in the secondary prevention of CHD. There were five drop-outs in the first year and 46 patients completed one year of therapy. An average of 2.791 of plasma was treated per patient every 7.7 days. Treatment was well tolerated and the incidence of side effects was small (2.9% of treatments). Mean pre-/post-apheresis LDL-cholesterol levels decreased from 283/120 mg dl-1 at baseline to 207/78 mg dl-1 and 203/76 mg dl-1 after 6 and 12 months, respectively. Mean pre-/post-apheresis HDL-cholesterol levels rose significantly over the course of therapy from 40.5/36.6 mg dl-1 to 44.8/39.7 mg dl-1 and 48.2/41.3 mg dl-1 after 0, 6 and 12 months, respectively. No major derangement of pre-apheresis haemostasis nor of haematological or clinical chemical parameters had occurred after 12 months of treatment. The data from this study support the feasibility of HELP-LDL-apheresis as an adjunctive therapy for lowering cholesterol levels in CHD patients refractory to cholesterol-lowering drugs while substantially improving the HDL/LDL ratio. PMID- 1936105 TI - Probucol increases cholesteryl ester transfer protein activity in hypercholesterolaemic patients. AB - Probucol, a widely used lipid lowering drug, reduces both low- and high-density (LDL and HDL) lipoprotein levels and can induce a regression of tissue lipid deposits in both animals and man. The suggested mechanism(s) involve the prevention of LDL oxidative modifications and, possibly, an improvement in the reverse cholesteryl ester transport system. Probucol administration to 10 hypercholesterolaemic patients increased the activity of the cholesteryl ester transfer protein (CETP) by 50%. The rise of CETP activity was significantly related with the plasma steady-state drug levels (r = 0.51, P less than 0.005), thus suggesting that probucol may directly stimulate CEPT synthesis and/or release. Furthermore, CETP activity was inversely related with HDL-cholesterol levels, both in the whole series of 10 patients (r = -0.56, P less than 0.001) and, more so, in the single individuals (r between -0.77 and -0.97), thus suggesting that the reduction of plasma HDL-cholesterol levels is a direct consequence of CETP stimulation. These findings support the hypothesis that an improvement in the reverse cholesteryl ester transport is a major mechanism of probucol and that this may explain the drug induced plasma lipoprotein changes. PMID- 1936106 TI - Familial defective apo B-100, characterization of an Italian family. AB - Familial defective apolipoprotein (apo) B-100 is a genetic disorder presenting with hypercholesterolaemia and abnormal low-density lipoprotein (LDL) that binds poorly to LDL receptors. This disease appears to be caused by a mutation in the apo B-100 gene. In the present study thirteen members of a family with moderate hypercholesterolaemia (250-350 mg dl-1) were investigated. Biochemical studies on cultured skin fibroblasts ruled out classical familial hypercholesterolaemia (FH, receptor deficiency). We then studied the interaction between LDL and their receptors by an in vitro cell binding assay. LDL from nine affected members displayed a reduced affinity (2.5-fold) for the receptor, and were less effective than LDL from control and unaffected members in suppressing LDL receptor expression and in stimulating cholesterol esterification. LDL from the affected members had normal electrophoretic mobility, size and chemical composition. Partial delipidation did not modify the LDL binding defect. The disorder is transmitted over three generations as an autosomal codominant trait and all the affected members are heterozygotes and hypercholesterolaemics. Analysis of DNA from family members showed a point mutation leading to an Arg to Gln substitution at amino acid 3500 of the mature protein that segregated with hypercholesterolaemia and LDL defective binding. We conclude that this family is affected by familial defective apolipoprotein B-100 (FDB). PMID- 1936107 TI - Regional variation in adipose tissue lipoprotein lipase activity: association with plasma high density lipoprotein levels. AB - The associations of adipose tissue lipoprotien lipase (AT-LPL) activity with body fatness and plasma lipoprotein levels were studied in the light of the recently described regional differences in AT-LPL activity. In this regard, heparin releasable LPL activity was measured in abdominal and femoral adipose tissues of 29 pre-menopausal women. Body fatness variables were all positively correlated with abdominal and femoral AT-LPL activities expressed per 10(6) cells. However, abdominal and femoral AT-LPL activities expressed per unit of cell surface displayed divergent association patterns with body fatness and plasma lipoprotein levels. Indeed, only abdominal AT-LPL activity remained significantly correlated with body fatness variables after adjustment for fat cell surface. Furthermore, whereas abdominal AT-LPL activity tended to be negatively correlated with plasma HDL-cholesterol levels, femoral AT-LPL activity was positively correlated with plasma HDL2-cholesterol (r = 0.40, P less than 0.05) concentration and with the HDL2-cholesterol/HDL3-cholesterol ratio (r = 0.49, P less than 0.01). These results demonstrate the importance of taking into account the regional variation in metabolic activity of adipose tissue when studying its associations with body fatness, and with plasma lipoprotein levels. The lack of association between abdominal AT-LPL activity and plasma HDL2-cholesterol levels lead us to suggest that AT-LPL activity may not be causally related with plasma HDL levels. PMID- 1936108 TI - Muscle protein synthesis in patients with rheumatoid arthritis: effect of chronic corticosteroid therapy on prostaglandin F2 alpha availability. AB - Using stable-isotope techniques, we measured rates of quadriceps muscle protein synthesis in twelve women with sero-positive rheumatoid arthritis. The results were compared to those from the normal limb of seven women with unilateral osteoarthritis of the knee. Six patients had never received corticosteroid immuno suppression, but the other six had taken an average of 8 mg Prednisolone per day for 9 years. Quadriceps atrophy was present in both sets of patients with rheumatoid arthritis (normal legs 444 +/- 182, rheumatoid 190 +/- 40, rheumatoid + steroid 300 +/- 110 micrograms protein/micrograms DNA, means +/- SD, both P less than 0.001). Muscle protein synthesis, calculated by comparing the incorporation of 13C-leucine into biopsy samples taken after an 8 h L-[1-13C] leucine infusion with the time averaged enrichment of blood alpha ketoisocaproate, was 0.056 +/- 0.005% h-1 in the patients not receiving steroids compared with 0.050 +/- 0.02% h-1 in normals (P greater than 0.05) indicating that muscular atrophy was primarily due to an increase in rate of muscle protein breakdown. Intra-muscular PGE2 concentration was increased in these patients (rheumatoid 0.12 +/- 0.06 ng mg-1 tissue, normals 0.06 +/- 0.03 ng mg-1 tissue, P less than 0.05). Patients taking corticosteroids had a markedly depressed rate of muscle protein synthesis (0.035 +/- 0.008% h-1, P less than 0.05) and reduced intra-muscular PGF 2 alpha concentration (P less than 0.01). We conclude that steroid therapy significantly influences the mechanism of skeletal muscle atrophy in patients with rheumatoid arthritis. PMID- 1936109 TI - The effect on body composition and exercise performance of home parenteral nutrition when given as adjunct to chemotherapy of testicular carcinoma. AB - This study has evaluated whether long-term and permanent total parenteral nutrition (TPN) can protect body composition and exercise capacity during iterated courses of chemotherapy (PVB) in men with testicular carcinoma. Thirty three men were randomly allocated by means of a computer based algorithm to receive either TPN (at hospital and home) during the entire chemotherapy period or to rely on spontaneous oral intake only. Nutrition status was assessed by measurements of whole body nitrogen (neutron activation), total body potassium, body water, urine creatinine excretion, loco-regional body nutrition indexes (AMC, TSF) and biochemical plasma concentrations (albumin, thyroid hormones). Whole body respiratory gas exchanges were measured during resting, submaximal and maximal exercise. TPN was prescribed on an individual basis in all study patients to cover 150% of their measured caloric need; nitrogen was given as 0.2 g N kg-1 day. All individuals were allowed to eat freely throughout the study. TPN patients were in overall positive energy balance (+850 Kcal day-1), while the control group was in negative balance (-532 Kcal day-1). This led to weight gain in the TPN group (+2.2 +/- 1.0 kg) while the control group lost significant weight (-4.2 +/- 1.1 kg). The average spontaneous oral caloric intake was 1014 +/ 153 Kcal day-1 in the TPN group and 1484 +/- 200 Kcal day-1 in the control group; total protein intake corresponded to 1.5 g protein kg day-1 in the TPN group and 0.7 kg day-1 in the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936110 TI - Insulin time-dependent effects on the leg exchange of glucose and amino acids in man. AB - Time-dependent effects of insulin on the leg exchange of glucose, lactate, glycerol, free fatty acids (FFA) and amino acids were measured in relation to oxygen uptake (leg and whole body) and whole body glucose assimilation including oxidation. Seven healthy males (58 +/- 3 years of age) were investigated before operation of uncomplicated inguinal hernia or varicose veins. Euglycaemic glucose clamp investigations with systemic hyperinsulinaemia between 100-120 mU1(-1) were used. Metabolic measurements were performed before and during hyperinsulinaemia at 2 and 6 h following the start of glucose clamp to evaluate the time-dependency of insulin actions. Whole body glucose uptake increased continuously for up to 6 h (from 4.7 +/- 0.7 to 8.0 +/- 0.8 mg/kg/min, P less than 0.01) despite stable plasma concentrations of glucose and insulin. This was also true for glucose oxidation. Whole body oxygen uptake did not change significantly during the clamp while the leg exchange of oxygen uptake did (from 5.9 +/- 0.86 mumol/100 g/min to 11.6 +/- 2.4, P less than 0.01). Insulin effect on leg blood flow was time dependent and increased two-fold (2.3 +/- 0.4 ml/100 g/min to 4.4 +/- 0.9, P less than 0.001) during clamp. The leg production of lactate increased continuously, accounting for approximately 15% of the glucose uptake across the leg, but the rise in arterial lactate did not reach the level of statistical significance. Plasma FFA concentrations decreased in a time-dependent manner during clamp, while the leg exchange of FFA switched rapidly to a stable net uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936111 TI - The effects of low dose insulin infusions on the renin angiotensin and sympathetic nervous systems in normal man. AB - To examine the effects of physiological insulin concentrations on the renin angiotensin and sympathetic nervous systems, healthy volunteers were studied by the euglycaemic glucose clamp technique with sequential 60 min 0.5 and 1.0 mU kg 1 min-1 insulin infusions and, subsequently, by a control infusion simulating clamp conditions. Plasma renin activity increased from 0.8 +/- 0.1 ng ml-1 h-1 basally to 1.0 +/- 0.2 ng ml-1 h-1 during the 0.5 mU infusion to 1.4 +/- 0.1 ng ml-1 h-1 during the 1 mU infusion but did not change during control infusion (0.9 +/- 0.3 ng ml-1h-1 to 0.9 +/- 0.2 ng ml-1h-1 to 1.0 +/- 0.1 ng ml-1h-1) (P less than 0.001 insulin vs. control by ANOVAR). Plasma angiotensin II increased during insulin (21.2 +/- 1.8 to 25.2 +/- 2.3 to 29.3 +/- 2.4 pg ml-1) but not during control infusion (24.0 +/- 2.8 to 23.6 +/- 2.6 to 23.5 +/- 2.5 pg ml-1) (P less than 0.001 insulin vs. control). Serum aldosterone did not change significantly during either infusion (insulin: 239 +/- 89 pmol l-1 to 237 +/- 50 pmol l-1 to 231 +/- 97 pmol l-1, control: 222 +/- 79 to 237 +/- 50 to 213 +/- 97 pmol l-1). Plasma noradrenaline increased to a greater extent during insulin (1.03 +/- 0.2 to 1.14 +/- 0.8 to 1.27 +/- 0.17 nmol l-1) than control infusion (0.86 +/- 0.09 to 0.97 +/- 0.09 to 0.99 +/- 0.09 nmol 1-1 (P less than 0.01 insulin vs. control). Changes in mean systolic blood pressure during insulin infusion were significantly different from control (+ 3 vs. -4 mmHg, P less than 0.001). In conclusion acute hyperinsulinaemia within the physiological range increases circulating hormones of the renin-angiotensin and sympathetic nervous systems and also increases systolic blood pressure. PMID- 1936112 TI - Assessment of iron availability using stable 54Fe. AB - This paper describes a method of quantitatively assaying the bioavailability of orally administered iron in order to promote haemoglobin synthesis in iron deficiency anaemia. The non-radioactive tracer substance 54Fe was employed. An experimental iron deficiency model was tested in 18 healthy male volunteers. The trial design made it possible to assess intestinal absorption and efficacy of iron substitution. The iron deficiency was experimentally induced by weekly phlebotomy. Two commercially available iron preparations with different rates of iron release were investigated at a dosage of 150 and 160 mg Fe2+ daily, respectively. In the first seven days of treatment, both preparations were administered in 54Fe-labelled form. Afterwards, iron substitution was given with the commercially available preparations. Measurements were made of erythrocyte utilization of 54Fe and plasma iron tolerance curves at the beginning of the periods in which the 54Fe-labelled product and the commercially available preparation were administered, and of haemoglobin and serum ferritin concentration curves over three months. The mean utilization of the iron administered was virtually identical for the two preparations (23 and 22%, respectively). Likewise, there was no difference with respect to the average daily increase in haemoglobin concentration in the blood (1.5 g 1-1). There was also no significant difference with respect to serum ferritin concentration curves. In contrast, the two preparations differed markedly with respect to the plasma iron tolerance curves. This suggests that evaluation of plasma iron tolerance curves alone is not suitable for comparative assessment of the therapeutic value of orally administered iron preparations. PMID- 1936113 TI - Efficiency of peptides and lipopeptides for in vivo priming of virus-specific cytotoxic T cells. AB - Synthetic peptides and a novel type of lipopeptide vaccine, both containing T cell epitopes recognized by Kd-restricted, influenza virus-specific cytotoxic T cells (CTL) were compared in their efficiency to induce virus-specific CTL in vivo. All attempts to induce virus-specific CTL with synthetic peptide (in the absence of adjuvants) failed. However, a latent immunization was observed, resulting in an increased response to the injected peptide seen only after boosting the recipients with immunogenic virus. In contrast, priming with synthetic lipopeptide vaccine (tripalmitoyl-S-glycerylcysteinyl-seryl-serine [P3CSS] coupled to peptide) was successful under most conditions, and matched the priming efficiency seen with infectious virus. The requirements for in vivo priming of virus-specific CTL using lipopeptide suggest that attachment of the lipopeptide to a hydrophobic entity, such as the cell membrane, is responsible for its efficiency. PMID- 1936114 TI - The chicken D locus and its contribution to the immunoglobulin heavy chain repertoire. AB - Sixteen D elements were characterized from the chicken genome, 15 of which are extremely homologous. Early expression of this D repertoire was studied for both DJ and VDJ alleles. No N diversification occurs at either DJ or VD junctions. Only P additions were observed, the length of which does not appear restricted to a dinucleotide. A selection for the almost exclusive usage of the first reading frame of the D elements takes place during B cell expansion in the bursa, in parallel with the selection of productive rearrangements. All three reading frames were observed for the DJ allele at each developmental stage, although some bias for the first reading frame occurs already at the junctional stage. The high incidence of D-D junctions observed (25% among DJ sequences) might represent the major functional contribution of this multigene cluster in a system in which diversity will be generated later on by successive superimposed gene conversions. Other possible functions are discussed. The onset of D diversification through gene conversion between day 15 and day 18 of embryonic development is further documented. PMID- 1936116 TI - Evidence for an association between human resistance to Schistosoma mansoni and high anti-larval IgE levels. AB - The anti-larval IgE antibody response of adolescents with high or low resistance to infection by Schistosoma mansoni was evaluated before parasitological cure with oxamniquine and over an extended post-treatment period during which the least resistant subjects regained high infections. IgE from most sera, taken at several bleeding times before and after treatment, reacted, on immunoblots, with a large number of antigens (Ag) in schistosomular tegument extract. A family of 120-165-kDa cross-reacting molecules and a 85-kDa Ag were the most prominent Ag. Some of these determinants were shown to be located on the outer tegumental membrane and to be accessible to IgE on living larvae. The comparison of IgE between the two study groups showed that IgE levels were on average six-to eightfold higher (p less than 0.01) in the sera of the most resistant adolescents whereas there was no difference in patterns of Ag recognition between study groups. In contrast to IgE, anti-larval IgG and IgM levels were either similar in both groups or higher in the least resistant subjects when these exhibited high reinfection levels. IgG that competed for the binding of IgE to larval Ag were detected in most sera and their levels were higher in the least resistant group after reinfection. Finally, the treatment had no observable long-lasting effects on the levels and on the specificity of the anti-larval IgE. Altogether, these observations can be taken as evidence supporting a role of IgE in human resistance to infection by S. mansoni. PMID- 1936115 TI - Terminal differentiation of human bone marrow cells capable of spontaneous and high-rate immunoglobulin secretion: role of bone marrow stromal cells and interleukin 6. AB - Human bone marrow (BM) is a major site for in vivo immunoglobulin (Ig) formation. A subset of BM cells has been described which is capable of high-rate Ig secretion for 14 days in vitro without additional stimuli. Therefore, it provides a suitable model for analyzing the terminal B cell differentiation within the BM. The pleiotropic cytokine interleukin (IL)6 was found to be essential for the further maturation of BM spontaneous Ig-secreting cells, as can be deduced from the following findings: (a) the addition of anti-IL-6 antibodies inhibited most of their Ig production; (b) when endogenous IL6 synthesis in the culture was restricted by using serum-free medium, the missing IgG secretion could be restored by the addition of exogenous IL6; and (c) active IL6 synthesis by BM cells in fetal calf serum-containing cultures was confirmed by direct quantitation (range 0.37-2.1 ng/ml). The presence of IL6 during the first 3 days of culture was necessary for the induction of Ig secretion. Since neither the proliferation of these cells was elicited by IL6 nor the inhibition of the DNA synthesis in these cultures prevented the IL6-mediated Ig secretion, IL6 must act on the BM Ig-secreting cells as a differentiation factor. The source of the endogenous IL6 was, apparently, an adherent cell, since most of the IL6 production was present in this cell fraction. In contrast, the nonadherent BM cell fraction contained all of the mature Ig-secreting cells even though it produced little, if any, IL6; the combination of both populations completely restored Ig secretion. Finally, homogeneous populations of fibroblastic stromal cell derived from long-term BM cultures were totally efficient in inducing Ig secretion by purified BM CD38+ cells; this phenomenon was also demonstrated to be IL6 mediated. Taken together, these findings appear to indicate that BM Ig secreting cells are not terminally differentiated, suggesting that their final maturation could be mediated by the BM microenvironment via the paracrine production of IL6. PMID- 1936117 TI - A B cell population that dominates the primary response to influenza virus hemagglutinin does not participate in the memory response. AB - The early primary B cell response of BALB/c mice to the influenza virus A/PR/8/34 (PR8) hemagglutinin (HA) is dominated by B cells that utilize a single V kappa gene in association with one of two closely related VH genes. We have used an anti-idiotypic reagent that recognizes a light chain-associated idiotope (23-1 Id) on these antibodies to follow their presence during the anti-HA response. Quantitation of 23-1Id+ antibodies at different time points during the anti-HA response indicates that the 23-1Id+ B cell response peaks early after primary immunization and is not re-induced by secondary challenge. Furthermore, 23-1Id+ titers in serum decay rapidly between the first and second week after immunization, and the HA-specific 23-1Id+ precursor B cell population does not significantly expand in the months following immunization. These results indicate that despite their predominance during the primary response, 23-Id+ B cells abruptly disappear from the response and do not mature into memory B cells. PMID- 1936118 TI - Chemotaxis of germinal center B cells in response to C5a. AB - An infiltrate of B cells and plasma cells is characteristic of certain chronic inflammatory lesions. However, mechanisms involved in the local accumulation of these cells have not been established. Efforts to demonstrate that B cells from normal animals can migrate in response to inflammation-induced chemoattractants have been inconclusive. The objective of this study was to determine if murine germinal center (GC) B cells could respond chemotactically to a C5a gradient. On successive days after secondary immunization, draining lymph nodes were harvested and the activated GC B cells isolated. These GC B cells were placed in modified Boyden chambers, incubated for 3 h and the distance the leading front of cells migrated through the filters was determined. The results show that GC B cells migrated to factors in zymosan- and lipopolysaccharide-activated serum. The migratory response demonstrated distinct kinetics. Cells isolated between 2 to 4 days after secondary immunization migrated, whereas cells isolated at day 0 and beyond day 6 did not. Checkerboard analysis revealed that the migratory response was attributable to both chemokinesis and chemotaxis. Anti-C5 inhibited the migration of day-3 GC B cells implicating C5 in the migration mechanism. Studies using recombinant C5a established that this C5 fragment was chemotactically active. In conclusion, GC B cells generally were not chemotactically active. However, at a particular stage of maturation B cells in the GC become responsive to C5a as a chemotactic agent. Thus, B cells from normal animals may respond chemotactically, and C5a may play a role in recruitment of recently activated B cells into inflammatory sites. PMID- 1936119 TI - Interferon-gamma and growth factor production by murine T cells derived from three different lymphoid tissues. AB - Various antigen-presenting cells and the environment in different lymphoid tissues have been suggested to influence the type of lymphokine produced by T cells. We have investigated the mitogen-induced proliferation, interferon-gamma (IFN-gamma) and growth factor production by cells isolated from spleen, mesenteric and peripheral (axillary, brachial and inguinal) lymph nodes (LN). We found that stimulation with concanavalin A or staphylococcus enterotoxin B induced IFN-gamma synthesis in spleen cells but not in LN cells. Proliferation and growth factor production were comparable in the three cell populations. The addition of the phorbol ester phorbol 12-myristate 13-acetate (PMA), which is commonly used as a substitute for accessory cells, did not influence the IFN gamma synthesis by LN cells. The growth factor production was, on the other hand, elevated by the addition of PMA. A high number of IFN-gamma-producing peripheral LN cells were obtained if they were stimulated in the presence of splenic adherent cells. The growth factor synthesis was marginally affected by the presence of these cells. Thus, splenic adherent cells provide a co-stimulatory signal to the T cell necessary for IFN-gamma synthesis. PMID- 1936120 TI - Allelic exclusion in transgenic mice expressing a heavy chain disease-like human mu protein. AB - Heavy chain diseases (HCD) are neoplastic proliferations of B cells which secrete truncated immunoglobulin heavy chains without associated light chains. These proteins are encoded by mutated genes which may also give rise to truncated membrane immunoglobulins. The neoplastic cells proliferate in vivo although they cannot bind any antigen, due to deletions in the variable domain of their antigen receptors. The reason for the clonal proliferation of HCD cells and the biological effects of the truncated membrane-bound chains are presently unknown. We wanted to determine whether the expression of HCD proteins would interfere with B cell development. To this end we made transgenic mice with a human mu gene, lacking the VDJ exon, that encodes a protein similar to that produced in two cases of HCD. Transgenic mice were also produced with a similar construct but encoding only the membrane-bound form of the truncated mu chain. Transgene encoded C mu proteins are expressed on the cell surface without associated light chains and are responsible for allelic exclusion of murine heavy chains. PMID- 1936121 TI - Correlation of lymphocyte lipid composition membrane microviscosity and mitogen response in the aged. AB - Healthy aged and young blood donors were investigated for the role of membrane lipid composition in the age-related increase in membrane microviscosity and decline of mitogen responsiveness. Membrane microviscosity was shown to correlate positively with membrane cholesterol/phospholipid molar ratios, which were significantly elevated in the elderly. A positive correlation also was confirmed between lymphocyte membrane microviscosity, which was measured using the probe 1,6-diphenyl 1,3,5-hexatriene, and phytohemagglutinin responsiveness of cells from the same donor. Using stepwise regression statistical analysis, the variables age, cholesterol, cholesterol/total phospholipid and phosphatidyl ethanolamine/phosphatidyl choline molar ratios were all shown to have a significant positive influence on membrane microviscosity, whereas total phospholipids had a negative effect. No statistically significant difference was seen in content of any single saturated or unsaturated fatty acid between young and old donors. After pooling, however, the proportion of all unsaturated fatty acids was significantly higher in cells from the elderly as a consequence of an increase of n-6 and n-3 polyunsaturated fatty acids. Changes in lipid composition and physical properties of lymphocyte plasma membranes may, therefore, be responsible (at least partially) for the diminution of immune reactivity in old age. PMID- 1936122 TI - Different types of allospecific CTL clones identified by their ability to recognize peptide loading-defective target cells. AB - Allospecific immune responses against the MHC of another individual are remarkably strong, due t a high number of responding T cell clones. Although it has been demonstrated that some allospecific cytotoxic T lymphocytes (CTL) recognize peptides presented by allogeneic MHC class I molecules, it has remained unclear whether MHC molecules can be recognized directly. We used the H-2b derived murine lymphoma mutant RMA-S, which has a defect affecting peptide loading of class I molecules, to test whether recognition by allospecific CTL always requires the presence of peptides. Three types of anti-H-2Kb CTL clones can be distinguished by their ability to lyse RMA-S target cells. Type A CTL clones efficiently lyse these target cells, the lysis by type B CTL clones is inefficient, and type C clones fail to lyse RMA-S. Up-regulation of the levels of H-2Kb density improved lysis by type B clones, but did not lead to lysis by type C clones. Some type A and B CTL clones apparently can recognize class I molecules devoid of peptides, while others are likely to recognize peptides which are not affected by the presentation defect of RMA-S. We suggest that type C clones are specific for peptides which are not presented by the mutant cells. The results show that the majority of alloreactive CTL recognize peptide/MHC complexes, while some CTL behave as if they can recognize class I molecules in the absence of MHC bound peptides. PMID- 1936123 TI - Temperature-induced stress abrogates co-stimulatory function in antigen presenting cells. AB - This study examines the effect of heat-induced stress on the function of splenic antigen-presenting cells. Heat shock (at 41 degrees C, 45 degrees C) profoundly inhibits the ability of this population to stimulate antigen-specific proliferation in ex vivo, or short-term cultures of T cells. This inhibition is not due to the release of suppressor factors from the antigen-presenting cells, nor to a lack of interleukin 1. Comparison of the effect of heat shock on presentation to a T cell hybridoma suggest that heat shock may affect the ability of antigen-presenting cells to deliver a co-stimulatory signal to the T cell. The implication of these findings in terms of the regulation of autoimmune phenomena is discussed. PMID- 1936124 TI - Regulation of immune response to inhaled antigen by alveolar macrophages: differential effects of in vivo alveolar macrophage elimination on the induction of tolerance vs. immunity. AB - A single intratracheal instillation of liposomes containing dichloro methylene diphosphonate into rats eliminated greater than 80% of the alveolar macrophage (AM phi) population, and the population was not significantly renewed during the ensuing week. AM phi depletion markedly increased local antibody production in the lung wall in pre-primed animals exposed to antigen aerosols. However, AM phi depletion did not affect the normal development of protective tolerance (particularly in the IgE antibody class) to inhaled antigen in immunologically naive rats. These results are discussed in relation to regional control of immune responses in the upper vs. the lower respiratory tract. PMID- 1936125 TI - V genes of oxazolone antibodies in 10 strains of mice. AB - One pair of V genes (V kappa 45.1 and V11) code for a great portion of phenyloxazolone (anti-phOx) antibodies in 10 strains of mice. This combination replaces the first-known major combination VHOx1-V kappa Ox1 in some strains, and is important in most strains. C57BL/10 and SJL mice have an additional subset of antibodies encoded by genes V kappa 45.1 and V13 (a relative of V11). All three genes involved (V kappa 45.1, V11 and V13) have "allelic" variation. Four alleles of V11 were found, one in Igh haplotypes a, c and g, the second in haplotypes d, j and n, the third in b, and the fourth in f. The most distant alleles d, j, n and f had 10 nucleotide differences out of 429 determined (97.7% homology). Only one allele of the V13 gene was found from anti-phOx hybridomas but two others have been published. Three alleles of the V kappa 45.1 gene were found; one in NZB mice (Ig kappa haplotype b) another in CE (haplotype f), and the third in eight strains including representatives of three Ig kappa haplotypes (a, c and e). The three alleles had greater than 99.0% homology. The V11 and V13 genes that code for anti-phOx antibodies in C57BL/10 and SJL mice were different from the related genes found from the C57BL/10 germ line. C57BL/10 mice must have a chromosome bearing two V11 and two V13 genes. RF mice were found to have two V11 genes, and both code for anti-phOx antibodies. Our data show that the majority of antibodies in the anti-phOx response are encoded by the same restricted collection of V genes in most mouse strains. Antibody responses appear to be no less heritable than other functions of the body. PMID- 1936126 TI - The role of C5a and antibody in the release of heparan sulfate from endothelial cells. AB - The activation of endothelial cells is thought to contribute to the host response to infection and to the pathogenesis of autoimmune disease. It was recently shown that antibody and complement can activate endothelial cells leading to cleavage and release of heparan sulfate from the cells. We show here that release of heparan sulfate from endothelial cells is mediated by antibody and the complement fragment C5a and that assembly of the membrane attack complex and lysis of endothelial cells is not necessarily involved. These data suggest that the generation of C5a in conditions such as autoimmunity and infection in which anti endothelial cell antibodies may also be present, might amplify tissue injury by a novel mechanism involving endothelial cell activation and loss of heparan sulfate mediated by antibody and C5a. PMID- 1936127 TI - The kappa/lambda ratio in surface immunoglobulin molecules on B lymphocytes differentiating from DHJH-rearranged murine pre-B cell clones in vitro. AB - The expression of kappa and lambda light chains in surface immunoglobulin (sIg) molecules on B lymphocytes differentiating from murine pre-B cell clones in vitro was analyzed. The four pre-B cell clones used represent a very early pre-B cell stage. They have their heavy chain loci DJ rearranged and their light chain loci in germ-line configuration. In order to grow in vitro, these clones require contact with stromal cells and the stimulatory activity of interleukin (IL) 7. Upon removal of IL 7 from the cultures, these clones differentiate within 3 days into sIg+ B cells. Between 7% and 12% of IgM+ B cells could be detected in these cultures. The majority (78%-92%) of the IgM+ B cells co-expressed kappa light chains. The percentage of lambda light chain expressing B cells was below detectable level. Upon lipopolysaccharide (LPS) stimulation, the percentages of IgM+ B cells increased dramatically (from 32%-64%). The majority (91%-97%) of the IgM+ B cells express kappa chains, but a very small percentage (3.1%-5.0%) express lambda. A similarly high kappa/lambda ratio was found in 418 hybridomas prepared from these LPS-stimulated B cells (388 kappa+ and 30 lambda+). Thus, the high kappa/lambda ratio characteristic of the mouse peripheral B cell repertoire is already evident in the antigen-independent transition from pre-B to B cells. PMID- 1936128 TI - Mechanisms of the tetrahydroaminoacridine effect on action potential and ion currents in myelinated axons. AB - 9-Amino-1,2,3,4-tetrahydroacridine (THA) in the range of 10-300 microM was shown to prolong the action potential in myelinated nerve fibres of Xenopus laevis. Voltage-clamp experiments showed that THA, besides reducing the Na+ and the K+ current, modified the Na+ current inactivation and the K+ current activation. The effects were frequency dependent. Quantitative models were developed and used in computer simulations of the THA effect on the action potential. The computations showed that the observed effects on the ion currents were sufficient to explain the observed prolongation of the action potential. The models further suggest that THA binds to Na+ channels in an open state and from the axoplasmic side while it binds to K+ channels in a closed state. The findings suggest an explanation to some aspects of the clinical effects of THA on Alzheimer patients. PMID- 1936129 TI - Photoaffinity labeling of plasma membrane proteins involved in the transport of loop diuretics into hepatocytes. AB - To identify proteins involved in the hepatocellular uptake of loop diuretics, [3H]bumetanide was photoactivated by light flash in the presence of either intact isolated rat hepatocytes, rat liver basolateral plasma membranes or integral membrane proteins extracted from the basolateral plasma membranes. Proteins of 52 54, 48, 33, 27, 25 and 23 kDa in sodium dodecyl sulfate (SDS) gel electrophoresis were radiolabeled on intact hepatocytes. On liver basolateral plasma membranes a 50-52 kDa protein was the most intensely labeled protein. After separation into integral and associated membrane proteins by extraction with Triton X-114, radioactive labeling was only found in integral membrane proteins with a molecular weight of 50-52 kDa. Photoactivated bumetanide irreversibly inhibited the hepatocellular uptake of cholate, taurocholate but not of serine. Binding proteins for photoactivated bumetanide were absent on AS 30-D ascites hepatoma cells. Labeling of all proteins was sodium dependent in intact hepatocytes but was sodium independent in plasma membranes. Labeling was prevented by non-labeled bumetanide and by the loop diuretics piretanide and furosemide. Labeling protection was further achieved with organic anions such as bromosulfophthalein, rifampicin, probenecid and by the bile acids taurocholate, deoxycholate and dehydrocholate. The radiolabeled proteins did not belong to the bumetanide sensitive NaCl/KCl co-transport system which apparently does not occur in intact isolated rat hepatocytes. PMID- 1936130 TI - Identification of an imidazoline-guanidinium receptive site in mitochondria from rabbit cerebral cortex. AB - In the present report, we used [3H]idazoxan to characterize imidazoline guanidinium receptive sites (IGRS) in mitochondria from rabbit cerebral cortex. When compared to the starting homogenate, [3H]idazoxan binding was higher (1.161 +/- 0.159 vs. 0.102 +/- 0.024 pmol/mg of protein) in a membrane fraction 6-fold enriched in cytochrome oxidase activity, a specific marker for mitochondria. In addition, the enrichment of [3H]idazoxan binding sites positively correlates with cytochrome oxidase activity in different membrane preparations (r = 0.977, P less than 0.001). In competition studies, [3H]idazoxan binding was completely inhibited by imidazoline and guanidinium derivatives but not affected by 10 microM epinephrine. Taken together, these data show the localization of IGRS in the mitochondria from rabbit cerebral cortex. PMID- 1936131 TI - Norepinephrine-induced phosphatidylcholine hydrolysis in intact rat aorta. AB - The present study tests whether norepinephrine induces the hydrolysis of phosphatidylcholine (PC) in intact vascular smooth muscle. Norepinephrine and the phorbol ester, phorbol myristate acetate (PMA), increased the formation of choline and phosphorylcholine in rat aorta. The norepinephrine-induced PC hydrolysis was inhibited by the protein kinase C (PKC) antagonist, 1-(5 isoquinolinylsulfonyl)-2-methyl-piperazine (H7). These results suggest that the diacylglycerol formed during the sustained phase of the contractile response to norepinephrine may be derived, at least in part, from PC hydrolysis. The hydrolysis may be mediated through PKC activation of phospholipase C and D. PMID- 1936132 TI - Angiotensin II induced biphasic inositol 1,4,5-triphosphate response in rat vascular smooth muscle cells. AB - We examined angiotensin II induced changes of inositol 1,4,5-triphosphate (Ins(1,4,5)P3) in cultured vascular smooth muscle cells from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) using a specific protein binding assay system. We observed a rapid biphasic Ins(1,4,5)P3 response, which peaked at 5 s and at 30 s after angiotensin II stimulation. At every period of time the Ins(1,4,5)P3 level of SHR was 2- to 5-fold higher than that of WKY. Thus, the Ins(1,4,5)P3 specific assay revealed a complex Ins(1,4,5)P3 response after angiotensin II stimulation and suggested the need for further investigation of the Ins(1,4,5)P3 metabolism following agonist stimulation in vascular smooth muscle cells. PMID- 1936133 TI - Intercranial reference lines versus the true horizontal as a basis for cephalometric analysis. PMID- 1936134 TI - Application of the orthodontic measurement and simulation system (OMSS) in orthodontics. AB - An orthodontic measurement and simulation system (OMSS) is introduced. The major component of the system consists of two force-moment sensors capable of measuring forces and moments in all three planes of space simultaneously. The two sensors are mounted on motor-driven positioning tables with full three-dimensional mobility. All mechanical components are built in a temperature-controlled chamber. A control programme executed by a personal computer performs various types of measurement which can be classified as absolute measurements (e.g. force deflection diagrams) and simulations of orthodontic tooth movement. By using the OMSS any orthodontic problem at the level of a two-tooth model can be analysed statically and dynamically. Besides other applications, the study evaluates three mechanical systems available for uprighting molars, namely a straight wire, a conventional uprighting spring, and a modified Burstone uprighting spring. It was found that the force systems produced by the straight wire and by the conventional uprighting spring showed a severe extrusive force component which may lead to occlusal trauma. The uprighting performance of the straight wire was inadequate. The conventional uprighting spring produced a large uprighting moment (17.8 Nmm), but also a strong lingual tipping moment (1.5 Nmm). The modified Burstone loop showed the best static and dynamic performance. It produced a force system with substantial uprighting moments in both the sagittal (11.6 Nmm) and frontal plane (4.2 Nmm). A slight intrusive force (0.09 N) might prevent the development of occlusal trauma during treatment. However, concern should be addressed to the fact that intra-oral adjustment of this uprighting spring is difficult because of its high susceptibility to minor modifications of its geometry. PMID- 1936135 TI - Potential application of shape memory plastic as elastic material in clinical orthodontics. AB - Polynorbornen, a shape memory plastic developed in Japan, has a glass transitional point of 35 degrees C. Once the environmental temperature exceeds the critical point, this plastic will begin to display an elastic property, then return to its original shape, if deformed. We examined whether the force generated during the elastic phase of polynorbornen could be used to displace human teeth. We found that the shape memory plastic wire of 1 mm in diameter stretched to two to three times of its original length at a temperature of 50 degrees C and a speed of 0.5 mm/sec would exert a relatively stable continuous light force of 119-156 g to move the teeth. This new material, compared with conventional elastic modules used in orthodontic therapy, exhibited a lesser degree of force degradation at a body temperature of 37 degrees C for a long period, and can be manufactured to near the tooth colour required. These advantages make feasible clinical application of the shape memory plastic in orthodontics. PMID- 1936136 TI - TMJ function with and without orthodontic treatment. AB - In order to evaluate the functional status of the stomatognathic system of former orthodontic patients, a review of current literature is given. In addition, a sample of orthodontically-treated subjects and a control group was investigated by means of clinical functional analysis. The figures found in the literature and the results of this study failed to reveal orthodontic treatment as a frequent cause of stomatognathic dysfunction symptoms. Instead, we found the functional status and occlusal parameters of our former orthodontic patients to be more harmonious than in the control group. PMID- 1936137 TI - Multilevel modelling of longitudinal cephalometric data explained for orthodontists. AB - Multilevel modelling of longitudinal data is an important new statistical technique. In this article some of the basic concepts and ideas of multilevel modelling are explained. The model is introduced by showing how individual and average growth can be modelled. The intercept, linear and quadratic coefficient, between and within variance, fixed and random part, and other concepts of multilevel modelling are explained. Attention is also given to the reading of statistical tables of the results of multilevel analysis. In the conclusion some of the advantages of multilevel modelling of cephalometric data are mentioned. PMID- 1936138 TI - Vertical facial growth: a longitudinal study from 7 to 14 years of age. AB - Multilevel analysis is used to describe the changes in vertical facial dimensions and their relationships in Dutch girls between 7 and 14 years of age. For the anterior face height (nasion-gnathion) and the posterior face height (sella gonion) a fourth degree polynomial was fitted. The mandibular plane angle (sella nasion-gonion gnathion) could be described with a second degree polynomial. Low correlations were found between the growth parameters (intercept and age coefficient) of the anterior and posterior face height, which points to independent growth and development of the anterior and posterior face height. The individual length and growth velocity (at age 10.8) of the anterior face height and the mandibular plane angle showed substantial correlations. It was concluded that changes during growth with regard to the mandibular plane angle are more strongly related to the anterior than to the posterior face height. PMID- 1936139 TI - A splint for immediate surgical orthognathic fixation and release during orthodontic treatment. AB - A splint has been designed for surgical use during the course of orthodontic treatment. The two-piece splint is ligated directly to the orthodontic arch wires. Surgically, the splint has the advantage of saving operative time, of ensuring precise location rapidly in all three planes, and allowing immediate release and replacement. Orthodontically, the splints allow a shorter preoperative phase of orthodontics, with the orthodontic treatment being completed postoperatively to ensure precise tooth positions and functional occlusion. PMID- 1936140 TI - Class III malocclusion: a comparison of extraction and non-extraction techniques. AB - A retrospective cephalometric study was made of the hard tissue changes in a group of 90 Class III, Skeletal III children, diagnosed as suitable for treatment by orthodontic means alone. Thirty-two were treated by a combination of upper incisor proclination and headgear to an intact mandibular dentition (Group 1), while in 28 the overjet was corrected with mid-arch extractions and Edgewise mechanics (Group 2). The remaining 30 children acted as controls (Group 3). Children were initially examined as male and female subgroups, and where no significant differences were seen data were pooled. In order to standardize the results, treatment/observation effects were presented as average changes per year. The three groups were essentially comparable pretreatment. Following overjet correction, the lower incisors uprighted in both groups, with an improved relationship to the A-Po line: the upper incisors were proclined in Group 1 only. Underlying skeletal changes were restricted to the mandible, which showed a downward and backward hinging, and an increase in lower face height. The improved mandibular position was significantly greater in the non-extraction group and was accompanied by an improvement in facial convexity. In addition, treatment could be started earlier and was completed in a significantly shorter time (Table 1). It would, therefore, appear that, in the short term at least, a non extraction/headgear approach has advantages over a standard mid-arch extraction/Edgewise technique. PMID- 1936141 TI - A stress analysis of the periodontal ligament under various orthodontic loadings. AB - The accurate modelling of teeth under orthodontic load in the laboratory has many shortcomings in that it has not been possible to integrate methods, such as three dimensional models, photo-elastic stress analysis, laser holographic interferometry, and animal studies, to give comprehensive and repeatable results. In this study, using a three-dimensional finite element model of a human maxillary canine tooth, the maximum principal stresses in the periodontal ligament produced by various orthodontic forces were determined. 1 Newton tipping forces produced stresses at the cervical margin of the periodontal ligament as high as 0.196 N/mm2 and apical stresses up to -0.034 N/mm2, while rotatory forces of two equal, but opposing forces of 0.5 Newton at the cervical margin of the crown produced cervical margin stresses ranging between -0.035 and 0.051 N/mm2, and apical stresses of between 0.0018 and 0.0027 N/mm2. These stresses are examined and discussed in relation to previous clinical, laboratory, and histological studies. PMID- 1936142 TI - Myths, masks, and mechanisms of facial deformity. PMID- 1936143 TI - Reference intervals for serum thyrotropin: dependence on the population investigated. AB - In order to elucidate possible differences of reference intervals in various populations, serum basal thyrotropin (TSH) was measured in euthyroid healthy volunteers (N = 170), in thyroid out-patients (N = 215), in geriatric (N = 354) and in seriously ill (N = 32) patients. The results, except in the healthy control subjects, were compared to the TSH responses (delta TSH) in the Thyrotropin Releasing Hormone test. Normal ranges calculated from the basal TSH of the euthyroid groups of different age were similar. There was a significant positive correlation of basal to delta TSH in all groups but the regression equations expressing the qualitative connection of basal and delta TSH were rather different. The basal TSH cut off point predicting a positive TRH-test (i.e. euthyroidism) with more than 95% probability was higher in the geriatric groups (greater than 0.7 mU/l versus greater than 0.4 mU/l in the other groups). In thyroid out-patients and geriatric patients a measurable (greater than 0.1 mU/l) basal TSH indicated measurable delta TSH (thus excluding clinical hyperthyroidism), while in seriously ill patients only a basal TSH greater than 0.2 mU/l was reliably predictive in this respect. Thus, various populations have different reference intervals for TSH. This fact must be considered when the sensitive TSH is used in different populations as the primary screening parameter for thyroid dysfunctions. PMID- 1936144 TI - Evidence for relaxin and progesterone synchronous secretion on days 13 to 17 of the oestrous cycle in sows. AB - Concentrations of relaxin in both the utero-ovarian vein (UOV) and jugular vein (JV) as well as those of progesterone and prostaglandin F2 alpha in the UOV were studied on Days 13-17 of the oestrous cycle in sows. Mean relaxin plasma concentrations in the UOV and JV were correlated (r = 0.55; P less than 0.001) and were significantly higher (P less than 0.01) in the UOV (1.67 +/- 0.07 ng/ml), than in the JV (0.59 +/- 0.1 ng/ml). The great similarity between relaxin and progesterone profiles was ascertained (r = 0.57; P less than 0.001). The steep decrease of progesterone plasma concentration on the day of luteolysis was observed together with synchronous relaxin concentration decline. A significant correlation between relaxin and PGF2 alpha plasma concentration was demonstrated one day before luteolysis (r = 0.41; P less than 0.001). PMID- 1936145 TI - Simple determination of iodine in small specimens of thyroid tissue. AB - This work describes a simple photometric determination of the iodine concentration in thyroid tissue, a method based on the well-known catalytic Sandell-Kolthoff reaction. The modified ceric arsenite reaction is very sensitive and does not require complicated laboratory equipment. It can be performed in any routine clinical laboratory if instructions are followed strictly. By means of this method iodine concentration can be determined even in small specimens, for instance puncture samples of thyroid tissue or thyroid glands of small animals (mouse). Previous to the analysis, the tissue is digested in a mixture of sodium chlorate and perchloric acid at 100 degrees C. Using this manner of digestion between 94 and 110% of iodine in the sample were recovered. Comparison with neutron activation analysis showed excellent agreement of the obtained values. PMID- 1936146 TI - Dormant metastases in medullary thyroid carcinoma. A case report. AB - Report on a patient in whom an extensively metastasizing medullary carcinoma of the thyroid was diagnosed at the age of 32 years. Noteworthy in her case history were watery diarrheas that had persisted for two years, suggesting that the medullary thyroid carcinoma had already existed for some time. Besides locoregional lymph node metastases, small foci of diffuse pulmonary metastases with lymphangitis carcinomatosa as well as osteoblastic skeletal metastases were present and intramammary metastases were detected later. The patient died from bilateral pleuropneumonia with empyema formation at the age of 47 years after an observation period of 15 years. During that period, no major changes in the pattern of metastatic spread were observed and one may therefore speak of "dormant" metastases in this case, although some manifestations showed increases and decreases in size. PMID- 1936147 TI - The effect of physical activity on bone turnover in young adults. AB - Physical activity has been suggested as one of the determinants of bone turnover and to prevent the involutional age related bone loss. However, the degree to which physical exercise is necessary to induce changes in bone turnover and calciotropic hormones have been widely discussed (Williams et al., 1984; Cook et al., 1987; Smith et al., 1985). The aim of this study was to examine the rate of bone formation measured by osteocalcin in 56 healthy volunteers before and after 4 and 8 weeks of physical exercise (PE) and its dependence on various parameters of calcium and phosphate metabolism. The studied group consisting of 44 men and 12 women, mean age 24.8 and 24.3 years, respectively, performed a standardized physical training of 8 weeks. Mean serum osteocalcin levels were significantly (p less than 0.01) reduced after 4 weeks (men: 2.26 +/- 1.8 ng/ml; women: 0.94 +/- 1.6 ng/ml) compared to the values before PE (men: 4.01 +/- 2.18 ng/ml; women: 1.69 +/- 1.7 ng/ml) and returned to normal values after 8 weeks. Similarly, magnesium levels (0.82 mmol/l) decreased significantly (p less than 0.01) after 4 weeks of PE (0.79 mmol/l), returning to normal values after 8 weeks. Concomitantly, there was only a slight, but significant fall of serum calcium from 2.48 +/- 0.07 to 2.45 +/- 0.07 returning to initial values again. Furthermore, serum phosphate increased slightly in men from 1.01 mmol/l to 1.13 and 1.15 mmol/l after 4 and 8 weeks, respectively. In contrast, alkaline phosphatase and serum creatinine remained in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936148 TI - Kurt Schubert 1919-1991. PMID- 1936149 TI - Estrogen secretion by the chick embryo ovary. AB - This is a review of work on estrogen secretion by the chick embryo ovary. The genetically female gonadal anlage secretes estrone and estradiol at the time of sex differentiation. Estradiol induces in a very short time interval the secretion of estradiol in the testis. However, it is not likely to play a role in normal ovarian sex differentiation, since neither anti-estrogens nor aromatase inhibitors disturb ovarian differentiation. Stimulation of estradiol secretion in vitro by LH is highest at early stages. Control of estradiol secretion by pituitary LH is suggested at early stages. PMID- 1936150 TI - Epidemiology and infection in famine and disasters. PMID- 1936151 TI - Application and evaluation of enzyme-linked immunosorbent assay and immunoblotting for detection of antibodies to Treponema hyodysenteriae in swine. AB - An enzyme-linked immunoassay (ELISA) has been developed to detect serum Immunoglobulin antibodies G and M to Treponema hyodysenteriae in vaccinated, experimentally infected and naturally infected swine. Naturally infected swine gave ELISA titres that were similar to experimentally infected swine, but were significantly less than the titres of vaccinated swine. When serum from naturally infected swine was used to probe nitrocellulose blots of sodium dodecyl sulphate polyacrylamide gel electrophoresed whole cell proteins of T. hyodysenteriae, the immunoblotting patterns showed IgG antibodies were produced against many T. hyodysenteriae protein antigens and against lipopolysaccharide (LPS). The IgG antibodies directed against LPS were serotype-specific for that LPS and could be used to identify the serotype involved in the T. hyodysenteriae infection in that herd. IgM immunoblots also reacted with the many protein antigens but were less specific for LPS antigen, with a substantial degree of cross-reaction between the LPS of all serotypes. The data demonstrate that a microplate enzyme-linked immunosorbent assay, coupled with immunoblotting, is a very specific and sensitive test for detection of antibody to Treponema hyodysenteriae in swine. PMID- 1936152 TI - Antigenic and genetic homogeneity of Streptococcus uberis strains from the bovine udder. AB - DNA- fingerprints (Hind III) of Streptococcus uberis field isolates from New York State and Europe showed substantial homogeneity, but were different to those of the type strain of the newly proposed psychrophilic species S. parauberis. S. uberis strains had major SDS-heat extracted antigens of molecular masses (Mr) less than 14, 40-41, 42-43, 59-61, 80-86 and 118-122 kDa following immunoblotting with rabbit hyperimmune sera. Bovine sera and milk reacted with the 40-41 and 118 122 kDa antigens. Variations in the Mr of particular bands were too unevenly distributed to permit formation of subgroups. Although cross reactive, the sizes of the antigens of S. parauberis strain NCDO 2020 were substantially different to those of S. uberis, the most prominent antigen having a Mr of 50 kDa. The antigenic and genetic data therefore strongly support the introduction of S. parauberis as a distinct species. S. uberis strains reacted with antiserum to Lancefield groups B, E, G and P, their grouping reactions showing no correlation with DNA and immunoblot fingerprints. Lancefield grouping of S. uberis therefore appears to have little value in identification. PMID- 1936153 TI - The use of the PhP-KE biochemical fingerprinting system in epidemiological studies of faecal Enterobacter cloacae strains from infants in Swedish neonatal wards. AB - The PhenePlate (PhP) biochemical fingerprinting system is an automated method for typing of bacteria, based on the evaluation of the kinetics of biochemical reactions, performed in microtitre plates. In the present study the PhP Klebsiella/Enterobacter (KE) system was evaluated for typing of Enterobacter cloacae and employed to study the epidemiology of faecal E. cloacae strains isolated from infants in 22 Swedish neonatal wards. The PhP-KE system showed a high reproducibility and discrimination for E. cloacae isolates. Among 64 epidemiologically unrelated E. cloacae strains, 49 distinct phenotypes were found, and the diversity index was 0.985. E. cloacae was found as a part of the dominating Gram-negative aerobic bacterial flora in 83 out of 953 infants studied. The incidences of E. cloacae colonization varied between 0 and 35% in different wards, but in contrast to previous data for Klebsiella spp. and Escherichia coli, there was little evidence of spread of particular strains in the wards. We also discuss two different measures of nosocomial transmission of bacterial strains: transmissible strains and epidemic index. PMID- 1936154 TI - Molecular epidemiology of plasmid patterns in Shigella flexneri types 1-6. AB - A total of 123 drug-resistant and drug-sensitive Shigella flexneri types 1-6, and their Escherichia coli K12 transconjugants were used for plasmid profile analysis by agarose gel electrophoresis. Resistance factors (R-factors) were further characterized by incompatibility testing. The overall distribution of small plasmids in S. flexneri showed that a cryptic plasmid of about 4.6 Kb was found in all serotypes, and a plasmid of about 4.2 Kb was found in serotypes 1-4. Shigella flexneri types 2, 4 and 6 showed a 6.5 Kb plasmid which correlated with SSu-resistance. All S. flexneri serotypes harboured large plasmids of about 217 Kb. Plasmid profile analysis of S. flexneri in Ethiopia showed a high degree of uniformity within individual serotypes. However, there was a limited variability which, at times, could be useful for epidemiological investigation. Shigella flexneri serotypes 1-6 harboured resistance plasmids with diverse molecular weights but mostly belonging to incompatibility groups N and X. PMID- 1936155 TI - The social and economic impact of salmonellosis. A report of a national survey in England and Wales of laboratory-confirmed Salmonella infections. AB - This study presents the findings of a national survey of 1482 cases of salmonellosis reported to Environmental Health Departments in England and Wales between August 1988 and March 1989. A questionnaire survey of ill individuals and the environmental health officers who investigated them sought information about costs which were imposed upon public health authorities, the health sector, individuals and their families and the costs to the wider economy in terms of lost production. Costs of 996,339 pounds were identified. Over half (507,555 pounds) resulted from lost production due to sickness absence and more than a third (392,822 pounds) were costs to the public sector which resulted from health care and local authority investigation of cases. The remaining costs (95,962 pounds), although the smallest proportion of the total, indicated that salmonellosis can have a significant impact on affected individuals and their families. PMID- 1936156 TI - The serological relationship between Yersinia enterocolitica O9 and Escherichia coli O157 using sera from patients with yersiniosis and haemolytic uraemic syndrome. AB - Sera from patients with yersiniosis, shown to contain antibodies to Yersinia enterocolitica O9; and sera from patients with haemolytic uraemic syndrome (HUS) caused by Escherichia coli O157, were used to investigate serological cross reactions between Y. enterocolitica O9 and E. coli O157. Lipopolysaccharide (LPS) was isolated from strains of Y. enterocolitica O9 and E. coli O157 and reacted with sera by immunoblotting and ELISA. Sera from patients with HUS contained antibodies to the LPS of E. coli O157 only; 80% of sera from patients with yersiniosis contained antibodies to the LPS of Y. enterocolitica O9 and E. coli O157. This one-way cross-reaction was also detected using hyperimmune rabbit antisera. PMID- 1936157 TI - Cockroaches (Blatta and Periplaneta species) as reservoirs of drug-resistant salmonellas. AB - A total of 221 cockroaches (Blatta and Periplaneta spp.), collected in hospitals, houses, animal sheds, grocery stores and restaurants, in various parts of South Kanara District, a south-west coastal region of India, were studied bacteriologically for the presence of various salmonellas. Salmonellas were isolated from 4.1% of these cockroaches. Nine strains of salmonellas were recovered, belonging to five serotypes--Salmonella bovismorbificans, S. oslo, S. typhimurium, S. mbandaka and S. braenderup, the former two being the commonest serotypes. All salmonellas were resistant to one or other of 11 antibacterial drugs used in the susceptibility test. Isolation of salmonellas from cockroaches collected from the livestock premises and human dwellings suggested that they may act as significant reservoirs of salmonella in nature. Recovery of serotypes, phage types and R-types that were commonly isolated from humans and animals of this locality, suggested a transmission role for cockroaches. By harbouring potentially pathogenic, drug-resistant salmonellas, these wandering arthropods may pose dangerous infective hazards to humans and animals. PMID- 1936158 TI - Jackdaws and magpies as vectors of milkborne human Campylobacter infection. AB - In 1990 we reported that milk bottles pecked by jackdaws and magpies were a probable source of human campylobacter infection. During April to June 1990 an extended study of campylobacter infections was carried out in the Gateshead area. Prior to the study a health education programme was undertaken in an attempt to reduce human infection. Fifty-nine cases of human infection were recorded and 52 were interviewed. Thirty were entered into a case control study which demonstrated a very strong association between consumption of pecked milk and human campylobacter infection (chi 2 = 12.6, P less than 0.0004). It was estimated that between 500 and 1000 jackdaws (Corvus monedula) were present in the area where milk bottles were pecked and 63 isolates of campylobacter were made from the bill and cloaca. Target bottles were put out in the early mornings and campylobacters were isolated from 12 of 123 pecked bottles. Typing of the campylobacters revealed a wide distribution of strains amongst birds, pecked milk and human infections. The health education programme had only limited success. PMID- 1936159 TI - An outbreak of pneumonia and meningitis caused by a previously undescribed gram negative bacterium in a hot spring spa. AB - An outbreak of infection caused by a previously undescribed Gram-negative bacterium affected people attending a hot (37 degrees C) spring spa in France in 1987. Thirty-five case of pneumonia and two cases of meningitis occurred. None of these patients died. Attack rates were significantly higher for patients above 70 years old and for male patients. An epidemiological comparison of the 26 hospitalized cases with 52 matched controls suggests that spa treatment early on the first day (OR = 4.8) and attendance at the vapour baths (OR = 10.7) were significant risk factors for acquiring the infection. Person-to-person spread was not thought to have occurred. The same bacterium was isolated from the hot spring water. All strains studied shows a single rRNA gene restriction pattern. Epidemiological data indicated that the thermal water was the source of infection. This outbreak stresses the need for increased surveillance of infections in people attending hot spring spas. PMID- 1936160 TI - Morphometrical parameters of gut microflora in human volunteers. AB - The morphology of faecal microflora of nine healthy human volunteers was studied by digital image analysis of microscopic slides. Weekly specimens were collected during an 8-week period. Seven morphometrical parameters were derived: the means and medians of components 1, 2 and 3, and morphometrical entropy. Statistically significant differences among subjects were found for means of components 1 and 2, medians of components 1, 2 and 3, and entropy. The stability in normal circumstances provides an excellent basis for the detection of pathological change in gut flora balance. PMID- 1936161 TI - Development of standardized inspections in restaurants using visual assessments and microbiological sampling to quantify the risks. AB - The relationship between visual inspections carried out by environmental health officers and microbiological examination was studied in 89 restaurants. Using 30 variables a standardized inspection procedure was developed and each of the premises was assessed in six main areas-structure and design, cleaning and cleanliness, personal hygiene, risk of contamination, temperature control, and training and knowledge about food hygiene. Selected foods and specimens from hands, surfaces, and wiping cloths were examined. There were significant associations between all six areas of the inspections. The structure and design were significantly related to the combined score from all the other areas (P less than 0.001). There were no highly significant associations between microbiological examination and visual assessments. The microbial contamination of wiping cloths, however, was related to the cleaning and cleanliness (P = 0.005). Microbial sampling provided additional information to inspections and was a valuable aid. Further development of this risk-assessment approach could provide an effective system for monitoring potential health risks in high-risk food premises. PMID- 1936163 TI - A mathematical model of rinderpest infection in cattle populations. AB - A mathematical model for the epidemiology of rinderpest was developed, starting from a simplified descriptive analysis of the disease. A formula for the calculation of the probability of infection of a susceptible animal was first established. A deterministic failure threshold of the infection was then deduced. Deterministic and stochastic approaches were adopted using iterative methods on a computer. These allowed a description of the spread and the variability of an infection process in a population to be made. An illustration of the use of this model showed that, in some cases, variability effects due to stochastic factors were very important. In these particular conditions, the use of the deterministic model alone was not adequate for a good description of the infection. Consequently, improvements of the model were proposed in order to make it more realistic and to allow its use for the evaluation of the efficiency of field operations. PMID- 1936162 TI - A serosurvey for HTLV-I among high-risk populations and normal adults in Egypt. AB - The prevalence of antibodies to human T-cell lymphotropic virus type I (HTLV-I) was determined in high-risk groups and normal adults in Egypt. Among 647 individuals tested, 6 (0.9%) were confirmed positive by western blot analysis. These included 2 (0.7%) of 279 drug addicts, 1 (3.3%) of 30 patients with sexually transmitted diseases, and 3 (2.2%) of 133 healthy individuals. Antibody was not detected in 47 blood recipients or 158 prostitutes. There was no correlation between sex or geographical location and HTLV-I infection. Fifty three of the 647 sera (8%) were initially reactive by ELISA, but only 12 sera were repeatedly reactive. Since only 4 of these repeatedly reactive sera were confirmed by the western blot, the frequency of false positives using the DuPont screening ELISA was 1.2% (8/643). Two additional sera, confirmed positive by western blot, had been reactive, but not repeatedly, by ELISA. In comparison to the prevalence of HTLV-I antibody among risk groups in many parts of the world, the prevalence in Egypt was low. PMID- 1936164 TI - The dynamics of microfilaraemia and its relation with development of disease in periodic Brugia malayi infection in south India. AB - Rates of acquisition and loss of Brugia malayi microfilaraemia were estimated using the parasitological data of a cohort of population in Shertallai, South India. The rate of acquisition of microfilaraemia was found to be dependent on age but not gender. The decline in the rate of acquisition of microfilaraemia in adults above 35 years could be due to the development of acquired immunity. The mean reproductive lifespan for the periodic Brugia malayi adult female worm was estimated to be 3.4 years and it was independent of host age and gender. The age specific estimated proportion of population at risk (microfilaria carriers who lost their microfilaria in course of time) of developing lymphoedema approximately mirrored the observed age specific prevalence of lymphoedema in the study population. On an average, 99% of population at risk developed disease in different endemic areas is compared and its epidemiological significance is discussed. PMID- 1936165 TI - Crystal structure of calf eye lens gamma-crystallin IIIb at 2.5 A resolution: its relation to function. AB - The crystal structure of gamma-crystallin IIIb (gamma C) from calf eye lens has been refined at 2.5 A resolution. The molecule of about 21 kDa consists of two similar domains. Each domain is composed of two motifs with the 'Greek key' topology which form a pair of four-stranded beta-sheets with an antiparallel packing. The molecule has three hydrophobic cores: one within each domain and one between them. Six of the eight functionally important cysteines are located within the N-domain, and only two in the C-domain. Several large clusters of charged residues are at the surface of the molecule. Surface residues Val 101, Met 103 and Leu 155 are important for packing of molecules in crystal medium and possibly in the lens. Features of the gamma-crystallin IIIb molecule which may be related to its function in the vertebrate eye lens are briefly discussed. An attempt has been made to correlate molecular characteristics with some general properties of the eye lens such as high density and refractive index gradients and strong stability of the lens during an organism's lifetime. PMID- 1936166 TI - Involvement of the N-terminal region in alpha-crystallin-lens membrane recognition. AB - Previous studies have demonstrated that alpha-crystallin binds specifically, in a saturable manner, to lens membrane. To determine the region of the alpha crystallin molecule that might be involved in this binding, native alpha crystallin from the bovine lens has been treated by limited digestion with trypsin, to produce alpha-A molecules with an intact C-terminal region, and a nicked N-terminal region. Compared to intact alpha-crystallin, trypsin-treated alpha-crystallin binds less avidly to lens membrane, suggesting that the N terminal region of the alpha-A molecule may play a key role in the recognition between lens membrane and crystallin. PMID- 1936167 TI - New method of ultrastructural localization of WGA-binding sites in the rabbit cornea using quick-frozen specimens followed by freeze-substitution. AB - Wheat germ agglutinin (WGA) conjugated with apo-horseradish peroxidase-gold was used as a probe for ultrastructural localization of N-acetyl-glucosamine and N acetyl-neuraminic acid residues of glycoconjugates in posterior stroma and Descemet's membrane of rabbit corneas. Ultra-thin sections of quick-frozen, freeze-substituted, and Epon or Lowicryl K4M-embedded tissue were used. Numerous WGA-binding sites were detected in the stromal matrix and Descemet's membrane in both embedding procedures. Labelling was more intense with low-temperature embedding in Lowicryl K4M than with Epon. Gold particles preferentially labelled the major collagen fibrils of the stroma but otherwise appeared uniformly distributed over both extracellular matrices, except in some areas of the stromal matrix that were barely labelled. Frequently, the inter-particle distance of gold particles on collagen fibrils corresponded to the banding period of type I collagen fibrils, suggesting that they point out keratan sulphate proteoglycans which contain WGA-binding sites. The combination of cryotechniques and post embedding procedures may be very effective for lectin histochemistry of the cornea and other eye tissues. PMID- 1936168 TI - Characterization of adenosine A1-receptor binding sites in bovine retinal membranes. AB - Using retinas prepared from freshly dissected bovine eyes, we have characterized the binding of the A1-selective agonist, [3H]PIA (N6-R-[3H](2 phenylisopropyl)adenosine). Specific binding was linear over a range of membrane protein concentrations from 0.10 to 1.0 mg, and accounted for an average of 80 90% of the total binding. At room temperature (24 degrees C), binding reached equilibrium at 60 min, and was reversible upon addition of an excess of cold ligand. Saturation analysis and Scatchard transformation revealed two apparent populations of receptor binding sites. The higher affinity site exhibited a Kd of 0.134 +/- 0.007 nM and Bmax of 26.18 +/- 3.06 fmol-1 mg protein. The lower affinity site exhibited a Kd of 21.83 +/- 4.39 nM and Bmax of 53.94 +/- 15.80 fmol mg-1 protein. Kinetic analysis of association and dissociation rates, performed at a low concentration of [3H]PIA, yielded a calculated affinity constant for the high affinity site of 0.2 nM, in agreement with saturation studies. Competition experiments with a number of purine nucleoside agonists and antagonists were performed, using radioligand concentrations of 1 nM or less to examine binding at the high affinity site, and revealed a rank order of potency consistent with the reported pharmacology of A1 receptors. We have also assayed for adenylate cyclase activity in this same preparation and determined that PIA inhibited forskolin-activated adenylate cyclase in a dose-dependent manner. Maximum inhibition (40%) was observed with 1 nM PIA, while 10 microM 8 cyclopentyl-1,3-dipropylxanthine, an A1 selective antagonist, completely inhibited this modulation by PIA. PMID- 1936169 TI - The effect of K(+)-conductance-blocking substances on the occurrence of retinal spreading depression. AB - Retinal spreading depression (SD) has been thought to be generated by an abnormal increase in [K+]o in the inner plexiform layer. When a retina isolated from bullfrog was immersed in a medium conditioned for SD (low Cl- Ringer's solution), spontaneous SDs periodically occurred at a fixed interval in the dark. The effect of K(+)-conductance blocking substances (Ba2+, Cs+, TEA and 4-AP) on the occurrence of SD was studied using the concomitant changes in the field potential (spreading depression potential; SDP) as an index. These substances increased the frequency of occurrence and decreased the amplitude of the potential. According to the Muller cell theory of SDP, an increase in [K+]o depolarizes the Muller cells and the resulting extracellular current generates the potential change. Since the small amplitude of the SDP reflects the decreased K+ current, it may be said that the K(+)-buffering capacity of the Muller cells was partially reduced by the substances and that the frequency of the SD occurrence consequently increased in order to clear accumulating [K+]o from neurons with the decreased buffering capacity. The present results lend a good support to the current Muller cell theory for the occurrence of SDP. PMID- 1936170 TI - Effect of light on endogenous ligands carried by interphotoreceptor retinoid binding protein. AB - Interphotoreceptor retinoid-binding protein (IRBP) is a vitamin A carrier present only in the extracellular material lying between the neural retina and the retinal pigment epithelium of vertebrate eyes. The amount of retinol bound endogenously by IRBP in this interphotoreceptor space is known to increase upon illumination. This finding led to the hypothesis that IRBP may act as a shuttle for vitamin A during the visual cycle that regenerates rhodopsin. In the present work, we separated IRBP from other retinoid-binding proteins in bovine interphotoreceptor matrix preparations by means of size-exclusion chromatography. IRBP's endogenous ligands were retained during this procedure and were then extracted into hexane and analysed by normal-phase HPCL. We found that IRBP carries, in a light-dependent manner, all the retinoid isomers involved in the visual cycle. For dark-adapted eyes the amounts of bound ligands are (in nmol per eye) 0.09 all-trans retinol, 0.11 11-cis retinol, 0.04 all-trans retinal, 0.16 11 cis retinal, and 0.07 retinyl esters. For light-adapted eyes the amount of all trans retinol was found to increase by a factor of five, and that of 11-cis retinal to decrease by a factor of four. (These eyes contain 3.1 nmol of IRBP, which does not change in amount with lighting conditions). Thus, the major endogenous ligand of IRBP is 11-cis retinaldehyde in the dark and all-trans retinol in the light. The data are consistent with a role for IRBP as a non selective scavenger and stabilizer of retinoids released from photoreceptors and pigment epithelial cells. However, it cannot be concluded from these data that IRBP is involved in directed transport of retinoids across the interphotoreceptor matrix, since there is no evidence for the appropriate spatial gradients in the ligands bound to the protein. PMID- 1936171 TI - Similar properties of taurine release induced by potassium and hyposmolarity in the rat retina. AB - Increasing external K+ concentration to 56, 75 or 100 mM stimulated taurine release by 3-, 7- and 11-fold, respectively. The K(+)-evoked release of [3H]taurine was markedly delayed, sustained and Ca(2+)-independent, in clear contrast to the usual neurotransmitter release pattern. These high K+ concentrations caused a marked increase in retinal cell volume which was prevented by removal of Cl-, or in hyperosmotic solutions. In these conditions [3H]taurine release also was abolished, suggesting an association of taurine efflux and cell swelling. Taurine release was also markedly increased 10- and 20 fold upon reduction of external osmolarity by 25 and 50%, respectively. Both, K(+)- and hyposmolarity-induced release were markedly inhibited by DIDS and quinidine. Total inhibition of the K(+)-evoked release was observed at 200 microM DIDS or 1 mM quinidine, whereas the drugs inhibited the hyposmolarity-evoked release by 50 and 68% respectively, at these concentrations. It is suggested that swelling is the signal for the K(+)-induced taurine release from rat retina. PMID- 1936172 TI - Analysis of concurrent glucose consumption by the hexose monophosphate shunt, glycolysis, and the polyol pathway in the crystalline lens. AB - A method based on 13C-NMR spectroscopy is described, in which the metabolism of [13C2]glucose was assessed in intact rat lenses. By analysing the ratio of 13C3/(13C2 + 13C3) lactate, a quantitative measurement of the hexose monophosphate shunt (HMPS) activity could be derived. Similarly, measurements of the time-dependent increase of lactate and sorbitol permitted the determination of the activity of the Embden-Meyerhof pathway and the polyol pathway, respectively. This method offers significant advantages over other biochemical and spectroscopic methods and allows for the first time a direct correlation between the activities of the polyol pathway and the HMPS. PMID- 1936173 TI - Study of crystallin expression in human lens epithelial cells during differentiation in culture and in non-lenticular tissues. AB - Crystallin expression in human lens epithelial cells in culture and a number of non-lenticular tissues was studied by the technique of immunoblotting using monoclonal antibodies. The expression of alpha A, beta 5 and beta 6 crystallins per unit number of cells increased with passage number while alpha B appeared to be constant Lentoid bodies derived from cultured human lens epithelial cells not only expressed gamma-crystallin and MP26 as previously demonstrated, but also produced alpha A, alpha B, beta 5 and beta 6 crystallins. In human non-lenticular tissues including ciliary body, vitreous body, neural retina, cultured retinal pigment epithelial cells and scleral fibroblasts, alpha B-crystallin was detected, but was undetectable in cornea and iris. Alpha A was present only in the lens. These studies demonstrate that HLE cells maintain the ability to synthesize crystallins through several passages. Following differentiation, they not only synthesize gamma-crystallin and MP26 but continue to express alpha- and beta-crystallins similar to differentiated lens fiber cells in vivo. Consistent with previous observations, the expression of alpha B-crystallin does not appear to be specific for the lens. PMID- 1936174 TI - Cell cultures of human ciliary muscle: growth, ultrastructural and immunocytochemical characteristics. AB - Primary ciliary muscle cell cultures derived from human donors (16-91 years) were established and characterized by comparing them with ciliary muscle in tissue sections using immunocytochemical and ultrastructural methods. Monoclonal antibodies against desmin, vimentin, alpha-actinin, smooth muscle (sm) specific alpha-actin and von Willebrand factor were used. In tissue sections of the ciliary body, ciliary muscle cells, vascular muscle cells, pericytes, endothelial cells and fibroblasts stain for vimentin. Both types of muscle cells and the pericytes stain for alpha-sm-actin, but only ciliary muscle cells stain for desmin. For tissue cultures, explants of the meridional and partly the reticular portion of the ciliary muscle were dissected and grown directly or after digestion of the explant with collagenase. Ten primary cell cultures with a typical hill-and-valley growth pattern similar to smooth muscle cells and two with a growth pattern similar to fibroblasts were established. All cultures could be subcultured up to the fifth passage. In fibroblast-like cultures 5-10% of the cells stained for alpha-sm-actin. Staining for desmin was not observed. In smooth muscle-like cultures, all cells stained positive for alpha-sm-actin. Desmin staining was not seen in growing non-confluent smooth muscle-like cultures. In confluent cultures, about 10% of the cells stained positive for desmin, preferentially in areas where the cells had formed hills. No culture stained for von Willebrand factor. Staining for alpha-actinin in smooth muscle-like cultures showed that the dense bands of the myofilaments were arranged in register, similar to the typical ciliary muscle cell morphology seen in tissue sections. Ultrastructurally, the smooth muscle-like cultures showed the typical morphology of cultured smooth muscle cells. We conclude that the smooth muscle-like cultures consist of ciliary muscle cells. PMID- 1936175 TI - Interphotoreceptor retinoid-binding protein (IRBP) in progressive rod-cone degeneration (prcd)--biochemical, immunocytochemical and immunologic studies. AB - Interphotoreceptor retinoid-binding protein (IRBP) is synthesized and secreted by photoreceptor cells and is thought to facilitate the transport of retinoids during the visual cycle as well as fatty acids essential to the maintenance of normal outer segment membranes. Proteins such as IRBP, which are unique to the photoreceptor cells in the retina, are prime candidates in the consideration of biochemical defects which could contribute to photoreceptor cell degeneration in man and animals. In this study, the association between IRBP and retinal degeneration was examined using the progressive rod-cone degeneration (prcd) mutant retina in dogs as an animal model. This study shows that loss of IRBP is not an early occurrence in prcd. IRBP is present in relatively normal amounts and distribution even at 1.7 years of age, a time when there is extensive visual cell disease and degeneration. By 2.7-3.0 years of age, IRBP loss correlates with the severity of the disease and concomitant loss of photoreceptor cells. IRBP immunoreactivity was present in the interphotoreceptor matrix (IPM) as long as inner segments were present to a significant degree. The late loss of IRBP immunoreactivity seems to be, therefore, the result of advanced degeneration and end-stage atrophy of the retina. In addition, immunological studies were carried out in order to examine the possible role of an autoimmune response against IRBP in the disease cascade. Normal, heterozygote and prcd-affected dogs had measurable antibody titers to IRBP, but there was no correlation between disease state and antibody levels. PMID- 1936176 TI - Analysis of human aqueous humor for epidermal growth factor. PMID- 1936177 TI - PEDF: a pigment epithelium-derived factor with potent neuronal differentiative activity. PMID- 1936178 TI - Plasma lipid abnormalities in the abyssinian cat with a hereditary rod-cone degeneration. PMID- 1936179 TI - The kinetics of tear fluid under the lower lid. AB - A very small drop of fluorescein solution was placed at the bottom of the lower fornix in human volunteers and its appearance in the tear film was measured. This was quite variable, but its appearance time averaged about 4 min and the peak of fluorescence 8 min. The time was shortened by blinking. The appearance time was too fast to be accounted for by simple diffusion in an unmixed tear fluid. Under normal circumstances, the release of the dye from the fornix is faster than its loss from the conjunctival sac, so that it does not seem to be a controlling factor in this loss. PMID- 1936180 TI - The normal human tear glycoprotein profile detected with lectin probes. AB - Tear samples were collected from 46 healthy volunteers evenly distributed according to sex and age (mean age 43.5 years). Samples were denatured in a Tris HCl sample buffer containing 2-mercaptoethanol and SDS, and applied to a gradient SDS-polyacrylamide gel for electrophoresis. The proteinaceous material was transferred to nitrocellulose by a semi-dry blotting technique, and the glycoprotein content subsequently visualized by incubation with four lectins (WGA, PHA, PSA and SBA) and staining with avidin horseradish-peroxidase. Glycoprotein bands were generally found to be significantly less frequent in persons under the age of 30 years. Apart from this the technique gave a uniform picture of the glycoprotein profile, with only modest differences according to age and/or sex. The technique may therefore be suitable for the detection of differences in the glycoprotein composition indicative of disease. PMID- 1936181 TI - Ultrastructure of human retinal cell transplants with long survival times in rats. AB - Human fetal retinas (6-12 weeks post-conception) were obtained from elective abortions, transplanted to rat retinas and examined by electron microscopy. The oldest transplants that form the basis of this report were obtained 40 and 41 total weeks post-conception. The host rats were immunosuppressed with cyclosporin A. The transplants developed according to their intrinsic, genetically determined timetable. The development was heterogeneous with some parts showing almost normal differentiation and others, little. Both rods and cones developed with inner and outer segments and synaptic terminals. In regions corresponding to the inner plexiform layer, bipolar cell processes were seen in the typical dyad arrangement. Likewise, amacrine cell processes formed typical conventional synapses. Serial synapses were seen, engaging amacrine cell synapses as well as a few reciprocal synapses at the bipolar cell dyads. Monad-type synaptic complexes, a sign of immaturity, were common in bipolar cell processes. Similarly, incompletely differentiated synapses of both the amacrine and bipolar cell types were often observed. Ganglion cell processes could not be identified with certainty. A structure with morphological characteristics similar to the inner limiting membrane was noted to form inside the transplant. Both epi-retinal and sub-retinal transplants were obtained. Transplant cells touched host photoreceptor cells or pigment epithelium without any obvious specializations. The host pigment epithelium microvilli were absent adjacent to the graft. However, graft cells did appear in the host retina, and nerve cell processes were observed to cross the membrane separating the transplant and host. PMID- 1936182 TI - Ultrastructure of the ciliary process vasculature in cynomolgus monkeys. AB - The ultrastructure of the ciliary process vasculature in cynomolgus monkeys is described with transmission electron microscopy. Special attention is paid to a special segment of the anterior arterioles (afferent segment) and to the end of the marginal venule (efferent segment)-vascular structures which have been described as haemodynamically important. The major arterial circle of iris (MACI), the exclusive blood supply of the ciliary processes, has only a one- or two-layered medium. A short distance after the anterior arterioles of the ciliary processes have branched off, these arterioles develop a characteristic segment of about 100 microns in length and which possesses a two-layered medium where prominent special myocytes lie on the adventitial side (afferent segment). Nerve endings with dense-core and large vesicles are closely associated to the vessel wall of these afferent segments. On the 'venous' side of the ciliary process vasculature, the very thin wall of the marginal ciliary process vessel becomes reinforced by a layer of myocytes in a segment which is located in the zone where the marginal vessel bends into the layer of the pars plana venules (efferent segment). Here, the endothelium is substantially thickened and filled with different-sized granules. Nerve endings with clear- and large dense-core vesicles lie around this segment. PMID- 1936183 TI - Elimination of immune precipitates from the rat corneal stroma: a histological study. AB - The pathogenesis of peripheral corneal lesions of immune aetiology, like Mooren's ulcer and catarrhal infiltrates, has been related to the formation or deposition of immune compkexes. The present investigation was undertaken to study the mechanisms involved in the elimination of immune precipitates from the cornea. Immune precipitates were induced by injecting human serum albumin (HSA) and rabbit anti-HSA serum into opposite sites of the rat corneal stroma. This resulted in a line-shaped opacity in the stroma, which remained visible by slit lamp for 7 days, and disappeared without clinical signs of keratitis and uveitis. At the ultrastructural level, the immune precipitates were clearly visible. Keratocytes in the vicinity of the immune precipitates appeared activated, as suggested by their less flattened appearance and well-developed rough endoplasmic reticulum. The arrangement of the collagen fibrils was not affected. Cells with a macrophage-like morphology were also present and contained electron-dense material, closely resembling the precipitate, suggesting phagocytosis. Separate corneas were injected with latex beads, which is known to induce migration of Langerhans cells into the cornea. Immunohistochemical analysis revealed that both latex beads and immune precipitates induced migration of macrophages (ED1+) into the rat corneal stroma. However, differences were observed with regard to the expression of MHC class II antigens by these ED1+ cells and the presence of complement deposits in the corneal stroma. ED1+ cells in corneas injected with latex beads were all MHC class II positive (OX4+), whereas most of the ED1+ cells at the site of the immune precipitates were negative (OX4-).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936184 TI - Autosomal dominant rod-cone dysplasia in the Rdy cat. 2. Electrophysiological findings. AB - Electroretinography was performed on cats affected with autosomal dominant rod cone dysplasia (gene symbol Rdy). In normal kittens it was found that retinal sensitivity increased and rod thresholds decreased as the animals matured. Electroretinogram (ERG) amplitudes were mature by 4.5 weeks and adult timing was attained by 6 weeks of age, consistent with the findings of other workers. In Rdy affected heterozygous kittens the ERG was absent or barely recordable using conventional corneal contact lens electrodes. However, the enhanced sensitivity of an intravitreal needle electrode permitted the recording of ERGs from affected kittens aged 4.5 weeks and older. The intravitreally recorded scotopic ERG in Rdy affected kittens was a very low amplitude, largely negative response with prolonged a- and b-wave times-to-peak (two to threefold longer than in comparable recordings from an age-matched normal kitten). The b-wave lacked oscillatory potentials and was relatively small so that the ERG was a-wave dominated. This was attributed to delayed and defective synaptogenesis in the outer plexiform layer of dystrophic retinas. In contrast to normal kittens, the b-wave threshold was higher than that of the a-wave in affected kittens. Photopic responses were unrecordable. The intravitreal ERG was barely recordable in a 5-month-old Rdy affected cat and was apparently extinguished by 7 months of age. In vitro electroretinography permitted a comparison of the photoreceptor responses (fast PIII) from the isolated retinas of 6-week-old control and Rdy-affected heterozygous kittens. Maximum fast PIII amplitudes were reduced by about 75% in affected retinas compared with age-matched normal retinas (P less than 0.005). The mean fast PIII time-to-peak, at maximum light intensity, in Rdy-affected retinas was prolonged by about 15 msec and was approximately twofold longer than the time-to-peak of normal retinas (P less than 0.005).4+ steeper slope with relatively greater prolongations in time-to-peak at lower luminances compared with normal retinas (P less than 0.025). These changes in temporal characteristics may be explained either by severe disorganization of photoreceptor outer segments or by altered phototransduction kinetics. PMID- 1936185 TI - Radio-isotopic determination of hydrogen peroxide in aqueous humor and urine. AB - The concentrations of hydrogen peroxide in the aqueous humor and urine of several animal species and humans have been determined. The determinations are based on peroxide-dependent decarboxylation of I-[14C]-alpha-ketoglutaric acid and measurement of the resulting 14CO2 by quantitating the radioactive disintegration. The levels of H2O2 in most animals varied between 5.0 and 41 microM for aqueous, and 115 and 187 microM for urine. The levels of peroxide in the urine of steer, cat and baboon were lower and fell out of the above range. In the aqueous of humans with cataracts, the levels ranged from 33 to 324 microM, the overall average being 189 +/- 88 microM. The source of such high levels in the aqueous of cataract patients is currently being studied. PMID- 1936186 TI - A quantitative study of the prenatal development of the aqueous outflow system in the human eye. AB - There is a multiplicity of theories on the development and differentiation of the human iridocorneal angle. Many have arisen from the need to explain the pathogenesis of primary infantile (congenital) glaucoma or other related developmental disturbances. The present study, which is the first light and electron microscopical morphometric analysis of human fetal eyes, was designed to determine the nature of the changes in various tissue components during trabecular anlage formation and differentiation (between 12 and 22 weeks of gestation). The results demonstrate that the trabecular anlage doubles in cross sectional area during this period. However, when circumferential growth is considered there is in fact a threefold increase in anlage volume. Cell density in sections decreases over the 10-week period, as does the number of cells per unit volume. However, employment of stereological analysis together with corrections for volume changes revealed a two to threefold increase in absolute number of cells per eye (2.8 x 10(5) to 7.5 x 10(5)). Relative and absolute volume data on the four major constituents of the trabecular anlage show that extracellular matrix increases in the most significant and predictable fashion (360% in absolute volume), with the increase in intertrabecular spaces being more variable (200%). The findings are discussed in relation to previous theories of trabecular meshwork development. PMID- 1936187 TI - Biosynthetic capacity of the human lens upon aging. AB - Lipid and protein biosynthesis were investigated in organ culture of human lenses from subjects ranging from 8 to 95 years old. A marked increase of protein and cholesterol content of the human lens with age was found. No significant linear correlation of age with either cholesterol or fatty acid synthesis was observed. Moreover, there are no indications that either synthesis declines with increasing age of the subject. Notwithstanding the large variety in age of the subjects, cholesterol and fatty acid synthesis of the individual lenses were correlated with each other in a positive linear way. Non-cataractous lenses as old as 80 years revealed a normal protein synthesis pattern as determined by incorporation of [35S]methionine into protein and analysis by 2D-gel electrophoresis. In addition, they maintained a high protein biosynthetic capacity. PMID- 1936188 TI - Transient hyperglycosylation of rhodopsin with galactose. AB - Rhodopsin's oligosaccharide chains contain predominantly two types of sugar residues: mannose and N-acetylglucosamine. In the present work, bovine and rat rhodopsin were analysed biochemically for the presence of a third sugar, galactose. Treatment of bovine rod outer segments (ROS) with galactose oxidase followed by reduction with tritium-labeled sodium borohydride revealed the presence of existing molecules of galactose on rhodopsin. Rats injected intravitreally with [3H]galactose and [14C]leucine and maintained in darkness were killed 1 hr, 6 hr, 1, 3 or 5 days following the injection. Retinas were collected for subcellular fractionation and rhodopsin from each of the fractions was purified by ConA sepharose chromatography and SDS-PAGE. During the first 6 hr, galactose selectively labeled rhodopsin in the Golgi-enriched fraction resulting in increased [3H]/[14C] ratios in both Golgi and ROS. The data suggested that trimming was occurring at the transition from Golgi to ROS. Furthermore, a decrease in isotope ratio in the ROS between 6 hr and 1 day suggested further trimming of rhodopsin after membrane assembly in the ROS. Additional in vivo experiments demonstrated existing molecules of galactose on rhodopsin's oligosaccharide chain using lectin affinity chromatography. Rats injected intravitreally with [35S]methionine were dark-adapted for 2 hr. Following subcellular fractionation of retinas, ConA purified rhodopsin from ROS was applied to one of two additional lectin columns: Ricinus communis agglutinin (RCA) or Griffonia simplicifolia I (GSA). Eight to nine percent of the labeled rhodopsin was bound to and eluted from RCA, whereas none bound to GSA, indicating the presence of a beta-galactoside. The RCA agarose eluted protein co electrophoresed with a rhodopsin standard and was light sensitive. Galactose was shown to be the terminal sugar on this subset of rhodopsin and was not capped by neuraminic acid. Binding of rhodopsin's oligosaccharide to RCA was abolished by pre-treatment with beta-galactosidase. Decreased binding of rhodopsin to RCA was observed following intravitreal injection of castanospermine but not swainsonine. Of those two inhibitors of glycoprotein trimming, only castanospermine would be expected to prevent the addition of galactose to the oligosaccharide. The association of galactose with rat rhodopsin appeared to be a transient one. At 2 hr, 8-9% of rhodopsin contained galactose, at 6 hr only 2.2% had galactose and by 24 hr less than 1% did. The galactose was trimmed from rhodopsin's oligosaccharide presumably after its role was complete. Separation of rhodopsin of the plasma membranes from rhodopsin of discs indicated that 75% of the galactose-containing rhodopsin was in the plasma membrane and only 25% was in the discs. These findings suggested a possible role for galactose in new disc formation with subsequent removal after the discs are sealed. PMID- 1936189 TI - Characterization of neuropeptide Y-like immunoreactivity in vertebrate retina. AB - We have determined the endogenous levels of neuropeptide Y-like immunoreactivity (NPY-LI) in retinal extracts from pigs, cats, rabbits, chickens, and frogs by radioimmunoassay (RIA). The NPY-LI levels varied among the species. The highest concentration was found in frog retina, where seasonal variations were seen, 861 +/- 31 pmol g(-1) wet weight in the autumn and 334 +/- 26 pmol g(-1) wet weight in the spring. Lower levels were demonstrated in chicken and pig retina, 4.1 +/- 0.4 and 3.6 +/- 0.3 pmol g(-1) wet weight, respectively. The lowest concentration was demonstrated in rabbit retina, 2.0 +/- 0.3 pmol g(-1) wet weight. (All values are expressed as mean +/- S.E.M.). The NPY-LI in pig, rabbit, chicken and frog retina was characterized by high-performance liquid chromatography (HPLC). The main part of the extracted NPY-LI had an elution volume close to that to the porcine NPY. We have also analysed the evoked release of endogenous NPY from frog retina, induced either with light flashes (3 Hz, 300 lx), or with potassium depolarization of the neurons (40 mM). Light flashes and potassium induced an increased release of NPY-LI of 61 and 77%, respectively. NPY-LI in the efflux had the same HPLC retention time as that extracted directly from the retina. PMID- 1936190 TI - A possible relationship between cataract, increased levels of the major heat shock protein HSP 70 and decreased levels of S-antigen in the retina of the RCS rat. PMID- 1936191 TI - Flow cytometric analysis of human erythrocytes: I. Probed with lectins and immunoglobulins. AB - A recent review (Aminoff, 1988) summarized the evidence for and against our hypothesis for the role of glycophorin in the senescence and clearance of mammalian red blood cells (RBC) from circulation. This hypothesis postulates the loss of sialic acid from RBC surface in two forms: (a) as vesicles containing the sialoglycoprotein glycophorin, and (b) as free sialic acid residues from glycophorin molecules remaining on cell surface. In this report we demonstrate the applicability of flow cytometric procedures to explore, at the cellular level, time-dependent changes on RBC surface with change in cell size, and with in vivo age. The RBC are probed with fluorescein isothiocyanate (FITC) labelled lectins and goat anti-human-IgG and -IgM. The relative intensity of fluorescence is correlated to the change in RBC size as measured by forward lightscatter. Reactivity of RBC with FITC-labelled wheat germ agglutinin can be inhibited with either 0.2M N-acetylglucosamine or by removal of sialic acid residues with neuraminidase. The properties of the smallest RBC correspond to those of the oldest RBC in their: (a) decreased reactivity with FITC-labelled lectins that recognize sialic acid residues, wheat germ and Limax flavus agglutinins, and (b) increased reactivity with FITC-labelled goat anti-human-IgG and -IgM. These results are compatible with our glycophorin hypothesis. Moreover, they suggest that the initial loss of sialic acid as glycophorin containing vesicles is gradual, while the subsequent step involving the loss of sialic acid residues is rapid and exposes multiple disaccharide galactose beta(1-3)N-acetylgalacosaminyl residues. These unmasked disaccharide sites are recognized by autoimmune IgG, IgM, and lectin-like receptors on macrophages resulting in the clearance of senescent RBC from circulation. PMID- 1936192 TI - Flow cytometric analysis of human erythrocytes: II. Possible identification of senescent RBC with fluorescently labelled wheat germ agglutinin. AB - In the first paper of a series (Gutowski, et al., 1991) we discussed the use of flow cytometry to follow at the cellular level the aging of red blood cells (RBC) in circulation, using fluorescently labelled lectins and goat anti-human-IgG and IgM. The Coulter Epics 541 was used for those studies. In this report we describe more extensive experiments using the Becton-Dickinson FACScan flow cytometer, and compare the results with those obtained with the Coulter Epics 541. By changing sample conditions from isotonic to hypotonic, compensation for differences of the two instruments was accomplished. We confirmed our previous observations that RBC react very strongly with fluorescein isothiocyanate labelled wheat germ agglutinin (FITC-WGA) and that there is little change in the intensity of fluorescence given by RBC of all sizes with the exception of the smallest. Reactivity with FITC-WGA is markedly decreased in the presence of competitive inhibitors of sialic acid or upon enzymatic removal of sialic acid from RBC. Removal of sialic acid is accompanied by increased reaction with peanut agglutinin (FITC-PNA). Flow cytometry was also used to monitor the enrichment of a population of smallest RBC (less than 0.05%), isolated from both counterflow centrifugation and the interface obtained from Histopaque separation. These smallest RBC showed low reactivity with FITC-WGA and higher binding of FITC-goat anti-human-IgG, and -IgM, and therefore represent the most senescent RBC, just prior to their clearance from circulation by the reticuloendothelial system. These observations are in compliance with the hypothesis that physiological desialylation of glycophorin is responsible for clearance of senescent RBC from circulation (Aminoff, 1988). PMID- 1936193 TI - Age-related decreases in the thyrotropin (TSH) responsiveness to thyrotropin releasing-hormone (TRH) stimulation and to the inhibitory effect of triiodothyronine (T3); in vitro study on superfused rat pituitaries. AB - The effect of age on the thyrotropic function was investigated in vitro by superfusing pituitary fragments obtained from 2-3-month- and 24-month-old male Wistar rats with medium 199 (GIBCO) and by measuring basal TSH secretion and TSH response to a 6-min pulse of TRH (10 nM): a/ in the absence and b/ in the presence of T3 (100 nM). TSH was measured by RIA in 3-min fractions with rat TSH materials from the NIADDK. The TRH-induced TSH release elicited by pituitary fragments from the old rats was decreased in comparison to that found in young animals. Addition of T3 to the superfusion medium did not alter basal TSH release but significantly decreased the TSH secretory response to TRH in the young rats. This response was not modified in the old animals. Our results suggest that aging induces not only a TSH hyporesponsiveness to TRH stimulation but also a decrease of this responsiveness to the inhibitory effect of T3 which could be related to a decreased TSH synthesis and to an age-related impairment of T3 action on the thyrotrophs. PMID- 1936195 TI - Effect of vitamin E on the accumulation of fluorescent material in cultured cerebral cortical cells of mice. AB - The effect of vitamin E on the accumulation of lipofuscin-containing fluorescent material in the mouse cerebral cortical cells in primary culture was studied. Fluorescent material was extracted in ethanol:diethylether (3:1) and autofluorescence intensity of the extracts was measured by a spectrofluorophotometer. Although vitamin E at the concentration of 0.005 IU/ml was not effective, 0.01 IU/ml vitamin E inhibited the accumulation of fluorescent material. Fluorescent material accumulation was reduced to 76.3-86.4% of the control level in 6-, 12-, or 18-day treatment of 0.01 IU/ml vitamin E. High doses of vitamin E (0.05 or 0.1 IU/ml) were toxic for cultured cells. Ethanol, the vehicle of vitamin E, at the final concentration of 0.005% was also effective on the reduction of fluorescent material accumulation (81.0% of the control level at 18 days). The inhibitory effects of vitamin E as well as ethanol on the accumulation of fluorescent material in cultured cells are explained by their nature as free radical scavengers. PMID- 1936196 TI - Age-dependent variations of the biosyntheses of fibronectin and fibrous collagens in mouse skin. AB - Skin explant cultures from hairless mice of increasing age were incubated with radioactive precursors in order to determine the age-dependent variations of the biosyntheses of fibronectin and fibrous collagens (types I and III). Total collagen synthesis expressed as a percentage of total protein synthesis did not vary with age but, if expressed as micrograms hydroxyproline per mg wet weight of skin, decreased by about 30% between 2 and 22 months of age. Hydroxylation of collagen, expressed as the ratio of 3H-hypro over 3H (pro + hypro) incorporated in freshly synthesized collagen, decreased with age by about 40% between 2 and 22 months of age. The proportion of type III collagen expressed as % of type I + type III collagens increased progressively with age by about 25% at 12 months to 60% at 22 months of age. Fibronectin biosynthesis, determined by immunoprecipitation of 35S-methionine labeled peptides in SDS-extracts of skin increased progressively with age from about 2% of total incorporated radioactivity in fibronectin at 2 months to 4% at 22 months. Plasma fibronectin, of hepatic origin, was shown already to increase with age in humans. It appears thus that the expression of genes coding for extracellular matrix macromolecules is under age-dependent regulation. This regulation appears to be different for the investigated macromolecules. PMID- 1936197 TI - The effects of ambient temperature on life span, lipid peroxidation, superoxide dismutase, and phospholipase A2 activity in Drosophila melanogaster. AB - Aging changes were examined in Drosophila melanogaster. Lifespan was determined in two strains of male and female Drosophila raised at 19 degrees, 24 degrees, and 29 degrees C. The results show an inverse relationship between lifespan and temperature. In addition, lipid peroxidation rates and superoxide dismutase activity were measured in homogenates and phospholipase A2 activity was determined in crude membrane samples prepared from this species. Temperature was found to be directly correlated with the rate of lipid peroxidation in each group. The longest-lived group, wild-type females, exhibited the lowest rate of lipid peroxidation at each temperature; whereas the shortest-lived group, vestigial wing males, displayed the highest rates of lipid peroxidation. Older (40-53 day) vestigial wing males also exhibited significantly higher superoxide dismutase activity than younger vestigial wing males (0-5 day) and higher phospholipase A2 activity than wild-type females of the same age. These results indicate that there is an association between lipid peroxidation rates and lifespan in Drosophila, and that aging changes may include an increase in superoxide dismutase and phospholipase A2 activity. These findings agree with the hypothesis that free radicals are involved in the aging process in Drosophila. PMID- 1936198 TI - Age-related increase in the uptake of acetylated low density lipoprotein into cultured endothelial cells from rat aorta. AB - A simple and reliable method for the separation of endothelial cells from the thoracic aorta of rats was established in the present study. The cultured endothelial cells separated by this improved explantation method showed typical characteristics of endothelial cells, morphology of cobblestone monolayer, immunoreactivity against antibodies to Von Willebrand's factor and angiotensin I converting enzyme, and the ability to uptake acetylated low density lipoprotein (LDL) labeled with 1,1'-dioctadecyl-1-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-Ac-LDL). The purity of the cultured endothelial cells separated by this method was over 98%, and the cells were maintained in culture for 3-4 months. Age-related changes of the uptake of DiI-Ac-LDL into the endothelial cells were then estimated by using the cultured endothelial cells separated from the aortas of young (4-8 weeks old) and old (95-100 weeks old) rats. When fluorescent DiI-Ac-LDL-labeled endothelial cells were sorted and analyzed by a cell sorter, the fluorescence intensity of the cultured cells from old rats was stronger than that of the cells from young rats. Therefore, the present results show that the uptake of the acetylated LDL into the endothelial cells increases with rat aging, and suggest the age-related increase in the acetyl LDL receptor in the endothelial cells of the rat aorta. PMID- 1936199 TI - Heritable variation for aggression as a reflection of individual coping strategies. AB - Evidence is presented in rodents, that individual differences in aggression reflect heritable, fundamentally different, but equally valuable alternative strategies to cope with environmental demands. Generally, aggressive individuals show an active response to aversive situations. In a social setting, they react with flight or escape when defeated; in non-social situations, they react with active avoidance of controllable shocks and with sustained activity during an uncontrollable task. In contrast, non-aggressive individuals generally adopt a passive strategy. In social and non-social aversive situations, they react with immobility and withdrawal. A main aspect of these two alternative strategies is that individuals with an active strategy easily develop routines (intrinsically determined behaviour), and consequently do not react (properly) to 'minor' changes in their environment, whereas in passively reacting animals it is just the other way around (extrinsically determined behaviour). It has become clear that active and passive behavioural strategies represent two different, but equivalent, coping styles. The coping style of the aggressive males is aimed at the removal of themselves from the source of stress or at removal of the stress source itself (i.e. active manipulation). Non-aggressive individuals seem to aim at the reduction of the emotional impact of the stress (i.e. passive confrontation). The success of both coping styles depends upon the variability or stability of the environment. The fact that aggressive males develop routines may contribute to a fast execution of their anticipatory responses, which is necessary for an effective manipulation of events. However, this is only of advantage in predictable (stable) situations, but is maladaptive (e.g. expressed by the development of stress pathologies) when the animal is confronted with the unexpected (variable situations). The flexible behaviour of non-aggressive individuals, depending strongly upon external stimuli, will be of advantage under changing conditions. Studies on wild house mice living under natural conditions show how active and passive coping functions in nature, and how the two types have been brought about by natural selection. PMID- 1936201 TI - Sexual maturation in female rats: hereditary, developmental and environmental aspects. AB - Two physiological components of sexual maturation, vaginal opening and first estrus, apparently evolve similarly in Wistar and Sprague-Dawley rats. However, a bimodal distribution in the frequency of the days of vaginal opening is observed within a given strain, which is less related to heredity than to the timing and type of experiment. In addition, when the modulators of sexual maturation are reviewed, it can be observed that sensitivity to external stimuli can vary even within a strain. For a defined set of breeding conditions, one group of rats can be more susceptible to changes in the lighting regimen and not be affected by controlled stressors, while another group responds more to stress and less to light. The reason for susceptibility to one rather than another environmental factor under similar breeding conditions is not understood. In that context, it is difficult to evaluate the role of heredity when we cannot understand the full impact of the environment, not to mention maternal influence in fetal and early life. Using two lines of psychogenetically selected rats, it was possible to show that they had differences in sexual maturation, which strongly suggested a genetic predisposition. Nevertheless, the question arises as to whether the genetic locus directly affects organs implicated in sexual maturation or whether it acts on some unknown factor which only secondarily modifies sexual maturation. In summary, there is more need to understand the role of the environment, including that of the mother early in fetal and neonatal life. It is suggested that the mechanisms underlying organ growth are set for a given species, while developmental and environmental factors fix the timing of vaginal opening and first ovulation. In the rat, there appear to be two times which are preferred for vaginal opening, given the laboratory conditions that have been used in the last 20 or so years: an early period, at 31-35 days, and a late period, at 36-40 days. An explanation for this dichotomy would be that a combination of parameters (not necessarily always the same) is needed for vaginal opening. These parameters oscillate during sexual maturation with different frequencies, which can achieve resonance to lead to vaginal opening and ovulation only during given periods. PMID- 1936194 TI - The effect of selective desalivation on wound healing in mice. AB - The effectiveness of wound licking in the acceleration of wound healing was evaluated in selectively desalivated mice. Rate of healing of experimentally induced cutaneous wounds was evaluated macroscopically by photography at 0, 2, 4, and 6 days after wounding. Sialadenectomy of submandibular and sublingual glands significantly slowed down wound healing in animals caged together compared to sham-operated controls. Separate caging as compared to caging in groups slowed down healing in sham-operated animals at day 2 but not at day 4 and 6. No effect on the rate of healing in sialadenectomized mice was observed in separate caging compared to mice caged in groups. Ligation of the parotid duct had an insignificant effect. The rate of wound healing of sublingual sialadenectomized mice was slower than that of sham-operated controls, but not as slow as those of sublingual and submandibular sialadenectomized mice. The results suggest that the rate of healing of experimentally induced cutaneous wounds of mice is slowed down when licking is prevented by separate caging which confirms previous reports. Licking with submandibular saliva seems to be more effective than sublingual saliva. Parotid saliva or minor salivary glands secretions are the least effective. PMID- 1936202 TI - Genetic determinants of individual differences in avoidance learning: behavioral and endocrine characteristics. AB - Bidirectional genetic selection for good and poor active avoidance learning in a shuttle box has been carried out in three independent laboratories using remarkably similar discrete-trial training procedures. The resulting strains are known as the Roman High and Low Avoidance (RHA and RLA), the Syracuse High and Low Avoidance (SHA and SLA) and the Australian High and Low Avoidance (AHA and ALA) strains, respectively. An additional unidirectionally selected strain, known as the Tokai High Avoider (THA) strain was developed in Japan using a free operant Sidman avoidance procedure in a Skinner box. This paper reviews the selection of the Syracuse strains, enumerates the various behavioral and endocrine characteristics of the strains, and compares them to the other similarly selected strains. The behavioral work suggests that genetic selection from diverse breeding stocks has resulted in common characteristics that differentiate the strains in the emotional, not learning, domain. The endocrine data, however, are somewhat at odds. The Syracuse strains differentiate one way with respect to endocrine function, and the Roman strains differentiate in the opposite way. We suggest, therefore, that the endocrine correlates are not tightly linked to the avoidance genotype. Genetic analysis of all of the selected strains for both the avoidance phenotype and the endocrine correlates will be needed to test this hypothesis. PMID- 1936200 TI - The behavior of the homozygous and heterozygous sub-types of rats which are genetically-selected for diabetes insipidus: a comparison with Long Evans and Wistar stocks. AB - Several aspects of spontaneous and conditioned behavior (food and water intake, locomotion and emotionality, passive and active avoidance acquisition and retention) of standard (albino and pigmented) rats, and rats heterozygous (HEDI) and homozygous (HODI) for diabetes insipidus, are reviewed. As would be expected, HODI rats have been repeatedly found to consume far more fluid than either HEDI or control rats. Pigmented rats appear to be more active than albinos. HODI rats exhibit less marked emotional responses than do control rats, among which the pigmented ones exhibit the highest emotionality. Light aversion is more evident in albino than in pigmented rats. No differences are found among HEDI, HODI and normal Long Evans rats. It is quite difficult to provide a clear-cut statement concerning inter-strain differences in passive avoidance behavior, possibly because of the variety of techniques employed. In any case, HODI rats do not perform worse than normal controls do. In one-way active avoidance paradigms, pigmented rats perform better than albinos, and the performance of HODI rats does not differ from that of controls. In two-way avoidance paradigms, albinos appear to outperform pigmented rats. Once again, there are no obvious differences between HODI and control animals. In addition to indicating that HODI rats may actually be less emotional than the other groups of rats reviewed here, the studies described once again fail to confirm the previously alleged functions of vasopressin in memory consolidation. PMID- 1936203 TI - Copper metabolism in the LEC rat: involvement of induction of metallothionein and disposition of zinc and iron. AB - The Cu concentration was about 40 times higher in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats aged 77 days (227.5 +/- 21.6 micrograms/g liver) than in Fischer rats (5.2 +/- 0.1 microgram/g liver). However, in the kidney and brain of the LEC rats, Cu concentrations were lower than in these organs of the Fischer rats. Cu concentration in the hepatic metallothionein fraction was about 130 times higher in the LEC rats than in the Fischer rats. The LEC rats showed markedly low concentrations of Cu in the serum and bile. It seems likely that excretion of Cu from the liver into the bile and blood (as ceruloplasmin) is inherently lacking in the LEC rat. PMID- 1936205 TI - Cell size of mammalian myocardia is not related to physiological demand. AB - Morphological characteristics of myocardial ventricular myocytes have been evaluated from 5 mammalian orders with resting heart rates ranging from 51 to 475 bpm. The purpose was to determine if morphological characteristics of the myocardia are related to the functional demand imposed on the cell as represented by the resting heart rate. Cell size is a constant among mammals of different sizes which have different physiological demands. In contrast, there is more mitochondrial area and less myofibrillar area per cell in animals with rapidly beating hearts than in animals with slower heart rates. Additionally, the mean cross sectional area of individual myofibrils is 30% larger in the cow as compared to the mouse. These findings combined with our previous studies indicate that the different functional requirements of myocardia from different mammalian orders are satisfied by intracellular adaptations of both a structural and biochemical nature. PMID- 1936206 TI - Early-life undernutrition causes deficits in rat dentate gyrus granule cell number. AB - Recently developed stereological methods have been used in experiments to examine the effects of two levels of undernutrition during early postnatal life on the total number of rat dentate gyrus granule cells. This study has shown that previously undernourished rats have significant deficits in the total number of this particular type of neuron. PMID- 1936204 TI - Reversible juvenile hormone inhibition of ecdysteroid and juvenile hormone synthesis by the ring gland of Drosophila melanogaster. AB - Juvenile hormone bisepoxide (JHB3) and juvenile hormone III (JH III) both inhibited the in vitro production of ecdysteroids by ring glands and brain-ring gland complexes from third instar post-feeding larvae of Drosophila melanogaster in a reversible manner, although JHB3 had greater efficacy. The JH III and JHB3 precursor, methyl farnesoate, did not affect ecdysteroid production. The in vitro synthesis of total detectable JH (JHB3 + JH III + methyl farnesoate) by the corpus allatum portion of the isolated ring gland was also inhibited reversibly in the presence of exogenous JHB3 and JH III, but not by methyl farnesoate. These data indicating negative feedback are in agreement with the accepted dogma of endocrine gland regulation. PMID- 1936207 TI - Genetic models in brain and behavior research. Part III. Extrapolations and perturbations. PMID- 1936208 TI - Genetic factors in neurotoxicology and neuropharmacology: a critical evaluation of the use of genetics as a research tool. AB - Animals have evolved a detoxication system to enable them to survive in a hostile chemical environment in which foods contain many non-nutrient chemicals. Detoxication depends on enzymes which are often genetically polymorphic. As a result, inter-individual variation is common, and in humans several Mendelian loci have been identified. However, most variation in response is probably due to the action of several genes. Genetic variation in response to the neurotoxin MPTP and to chemically and physically-induced seizures is reviewed. In the former case, differences between pigmented and white mouse strains have been noted which are consistent with the hypothesis that humans are more sensitive than mice or rats because of the presence of melanin in human brains. However, variation in sensitivity probably also depends on other genes. In the case of audiogenic seizures, a single locus has been identified and mapped, but its relationship with seizures induced by other agents is not clear. Genetic variation in response to alcohol is also discussed. The failure of most toxicologists to consider genetic variation as a potentially confounding variable, and as a powerful research tool, is discussed critically in relation to non-repeatability of research on the neurotoxic effects of lead, and in relation to the genetic variation in MPTP, seizures, and alcohol response already noted. It seems clear that genetic methods provide a powerful research tool which is largely being ignored by toxicologists. PMID- 1936210 TI - Extracellular and cell-associated localizations of plasminogen activators and plasminogen activator inhibitor-1 in cultured endothelium. AB - The extracellular localizations of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were examined in cultured bovine capillary endothelial cells (BCEs) by an immunofluorescence method using BCEs treated with or without saponin and focal contact preparations. The specific immunofluorescence of cell surface uPA showed a patchy or strand-like distribution and was colocalized with vinculin strands indicating that uPA secreted from BCEs was mainly deposited at the cell surface of focal contacts. BCEs at a subconfluent density showed a higher intensity of specific immunofluorescence for uPA than when they were at a confluent density. tPA was observed over the dorsal surface of cultured BCEs and accentuated at their margins, suggesting that tPA was diffusely distributed on the luminal surface of BCEs in vivo. PAI-1 was distributed in the extracellular matrix under cultured BCEs. These findings suggest that uPA and PAI-1 are located under BCEs participating in the regulation of proteolytic activities provoked by plasminogen PAs-plasmin system in vivo. The localization of tPA appears to be consistent with its function, which is to maintain the fluidity of the blood and to initiate thrombolysis in vivo. PMID- 1936209 TI - Genetic and environmental influences on reactive and spontaneous locomotor activities in rats. AB - Paired groups of rats (derived from divergent, selective breeding or living in divergent environmental conditions) were compared with regard to locomotor activities. Intrapair differences were found to vary non-systematically, depending upon whether the rats were initially exposed to a test-environment with or without a slight environmental modification (reactive activities), or were allowed to habituate extensively to the environment (spontaneous activity). Since the behavioral patterns were found to represent distinct entities, this pointed to the necessity of differentiating clearly between spontaneous and reactive activities and indicated, once again, that both genetic and environmental influences are important in these behaviors and must be taken into account. Accepting and controlling for these variables makes it possible to use the factor of individual differences in laboratory animal behavior to advantage. PMID- 1936211 TI - Prevention of 4-pentenoic acid-induced liver injury in rats by 16,16-dimethyl PGE2. AB - 16,16-Dimethyl PGE2 (dmPGE2) is known to protect against cellular damage in various tissues. Histological and biochemical approaches were used to examine the effect of this prostaglandin on hepatocellular damage in an experimental Reye's syndrome model produced in rats by 4-pentenoic acid. Chronic intraperitoneal administration of 4-pentenoic acid induced an accumulation of fatty droplets throughout the hepatic lobules along with mitochondrial abnormalities including swelling, disappearance of christae, and heterogeneity of matrix. These abnormalities were more intense in the marginal zone and successively decreased nearer to the central vein. Such hepatic abnormalities were markedly reduced by the combined administration of dmPGE2 with 4-pentenoic acid. Biochemical examination confirmed that dmPGE2 was able to inhibit the accumulation of hepatic triglyceride seen after the treatment with 4-pentenoic acid alone. These results indicated that dmPGE2 can prevent characteristic hepatocellular damage in this experimental Reye's syndrome model, suggesting that the involvement of prostaglandins should be taken into account in discussing the etiology and management of this syndrome. PMID- 1936212 TI - Alteration in molecular structure of cytoskeleton proteins in griseofulvin treated mouse liver: a pressure tuning infrared spectroscopy study. AB - Different liver diseases are associated with modifications in hepatocyte cytoskeletal organization and formation of Mallory bodies (MBs). Since the structure of a protein is critical for its function, we studied the changes in the molecular structure of the cytoskeletal protein in the liver from mice fed griseofulvin (GF), which is a good animal model for studying liver disease. Using pressure-tuning infrared spectroscopy we compared the infrared spectra of the cytoskeletal proteins from control liver and griseofulvin treated liver. The results show that the overall structure of the cytoskeletal protein was modified by the griseofulvin treatment. A relative increase in the amount of alpha-helices to beta-sheets was observed in the liver cytoskeleton from the GF-treated mice. Moreover, the random coil and the turn segments were dramatically decreased compared to controls. Pressure-induced modifications including denaturation were irreversible in the control samples whereas they were reversible in the griseofulvin-treated samples. These changes reflect important fundamental modifications in the molecular structure of the cytoskeletal proteins in the griseofulvin-treated hepatocytes. We suggest that these changes are related to the modification of the organization of intermediate filaments and the formation of MBs that occur in the GF-treated liver. PMID- 1936214 TI - Elastase digestion of normal and pseudoxanthoma elasticum lesional skin elastins. AB - Pseudoxanthoma elasticum (PXE) is a heritable disorder of connective tissue that is characterized by redundant folds of skin in flexural areas. There is considerable evidence that suggests that the elastic fiber is the main site of the abnormality although the primary molecular defect has not been identified. The aim of this study was to identify differences between PXE and normal skin elastins. Elastins from normal, nonsolar-exposed skin, and pseudoxanthoma elasticum lesional skin were purified and their solubilization by pancreatic elastase was compared. Results demonstrated that elastin derived from normal skin was more susceptible to proteolytic cleavage than elastin purified from either pseudoxanthoma elasticum lesional skin or ligamentum nuchae. Pretreatment of the lesional elastin with testicular hyaluronidase increased its solubilization two fold and generated a unique 15,000 Da molecular weight fragment. Elastin prepared from PXE skin may contain bound glycosaminoglycans which interfere with elastase activity. The susceptibility of normal skin elastin to proteolytic degradation may have implications in the study of aging skin. PMID- 1936213 TI - Evaluation of antiepileptic drug effect on membrane fluidity. AB - Many drugs and chemicals have been shown to induce modifications of the physicochemical properties of cellular membranes. In this study we investigated the changes in fluidity of erythrocyte membrane from epileptic patients under different pharmacological treatments, with respect to healthy controls, by using trimethylammonium-1,6-diphenyl-1,3,5-hexatriene (TMA-DPH) fluorescence polarization. The increase in TMA-DPH fluorescence polarization values observed in epileptic patients indicated a decrease in membrane fluidity. Since the analysis of erythrocyte membrane composition did not reveal significant differences between the two groups studied, a correlation with membrane lipoperoxide content was tried, as different drugs and chemicals elicit in vivo alterations resulting in peroxidation of membrane lipids. Therefore the presence of peroxidation products in the blood and the possible correlation with membrane lipoperoxide were studied. Although a direct causal linkage cannot be proved we can hypothesize that exogenous compounds such as antiepileptic drugs could modify membrane fluidity by increasing membrane lipid peroxidation. Moreover the increase of peroxidative products in the blood could indicate that the peroxidative damage might propagate through the formation of new free radical species. The possibility of using erythrocyte membrane as a model system to analyze antiepileptic drug side effects is advanced. PMID- 1936215 TI - Endotoxin hepatotoxicity augmented by ethanol. AB - To determine whether alcohol increases endotoxin hepatotoxicity, we administered ethanol (4.8 g/kg body wt in 4 ml of water) to rats through a gastric tube, then immediately injected endotoxin (2, 2.5, or 3 mg/kg body wt). In the rats pretreated with ethanol, the injection of 2 mg/kg body wt of endotoxin induced a slight rise of serum transaminase. However, when 2.5 mg/kg body wt of endotoxin was given, there were no significant histopathological or biochemical differences between the rats pretreated with ethanol and those pretreated with water. Moreover, there was no significant difference in mortality rates between the rats pretreated with ethanol and the controls when 3 mg/kg body wt (LD50) of endotoxin was injected. These results suggest that acute administration of alcohol enhances endotoxin hepatotoxicity when the dose of endotoxin is small, but that the effect of alcohol is masked when larger doses of endotoxin are given. PMID- 1936216 TI - Oral contraceptive pill use after an initial visit to a family planning clinic. AB - A retrospective study of 1,311 women making initial family planning visits to metropolitan-area health department clinics found that many women switch methods or discontinue use in the first year following the clinic visits. Among a subgroup of women, most of whom selected the pill as their primary method and who used the pill for at least one of the months in the study period, almost half either changed methods or used no method at some point during a follow-up period averaging eight months. This includes 13 percent of women who made two or more changes. In addition, only 42 percent said they took a pill every day, and only half of these said they always took their pill at about the same time every day. Despite such irregularities, pill users were approximately one-third as likely to get pregnant during the study period as women making an initial family planning visit to a health department clinic who did not use the pill at all. PMID- 1936218 TI - Intergenerational transmission of school-age parenthood. AB - A long-term follow-up of a group of black New Haven women who were young mothers in the late 1960s revealed that the majority of their offspring had not become parents by age 19. The offspring who experienced early parenthood were most likely to be female and to report significant depressive symptoms. Of those children--both male and female--who did become young parents, many were the offspring of women who had moved out of their mothers' homes within 26 months of the child's birth, and of women who reported suffering from lifetime depression. The data indicate that emotional deprivation, particularly at an early age, may predispose adolescents to seek emotional closeness through sexual activity and early parenthood. PMID- 1936217 TI - Unplanned childbearing and family size: their relationship to child neglect and abuse. AB - Mothers from 198 low-income, female-headed families enrolled in child protective services because of child abuse or neglect were compared with an equal number of age-matched controls, to determine if unplanned childbearing and family size increase the risk of child neglect or abuse. Logistic regression analyses suggest that unplanned childbearing increases the risk of child abuse but not of child neglect. Large family size significantly raises the risk of both types of maltreatment, although this factor had a greater effect on the risk of abuse than on the risk of neglect. Finally, unplanned childbearing appears to be indirectly related to abuse through its effect on family size. PMID- 1936220 TI - Court upholds Title X ban on abortion information. PMID- 1936221 TI - Harriet Fleischl Pilpel. PMID- 1936222 TI - Non-invasive mechanical ventilation for cystic fibrosis patients--a potential bridge to transplantation. AB - The case histories of six cystic fibrosis patients awaiting heart-lung transplantation are reviewed. They all deteriorated with severe hypoxia and hypercapnia before donor organs became available. Nasal intermittent positive pressure ventilation was used in preference to conventional ventilation with excellent results in four patients. There were no episodes of hypotension or toxaemia and the patients were in a stable condition at the time of surgery and made an excellent post-operative recovery. The patients who were transplanted and the patient who died, for whom suitable donor organs did not become available, probably had a more comfortable time than they would have done if treated with conventional ventilation. This method of ventilation appears to be a useful bridge to transplantation when a patient suddenly deteriorates. It gives them a chance of survival for a few more days or even weeks during which time an urgent search for donor organs can be made. This is also a very cost effective method of ventilation and does not encroach on conventional Intensive Care Unit (ICU) facilities. PMID- 1936219 TI - An ounce of prevention ... STDs and women's health. PMID- 1936223 TI - Aerosolized endothelin-1, but not its C-terminal hexapeptide, causes airway narrowing in the rat. AB - We investigated the effects of aerosolized endothelin-1 (ET-1) and of its C terminal hexapeptide, ET-(16-21), on the pulmonary mechanics of anaesthetized spontaneously-breathing rats. ET-1 inhalation caused a concentration-dependent increase in pulmonary resistance (RL) and decrease in dynamic lung compliance (Cdyn). In control conditions RL and Cdyn were 0.17 +/- 0.04 cmH2O.ml-1.s (mean +/- SE; n = 6) and 6.25 +/- 0.66 ml.cmH2O.1. respectively. After ET-1 4 x 10(-5) M RL and Cdyn averaged 1.45 +/- 0.28 cmH2O.ml-1.s (p less than 0.05) and 1.12 +/- 0.36 ml.cmH2O-1 (p less than 0.05), respectively. The pulmonary responses to ET-1 lasted up to 60 min. By contrast, ET-(16-21) inhaled up to a concentration of 10( 3) M did not affect pulmonary mechanics. These results indicate that the bronchoconstrictor activity of aerosolized endothelin-1 in the rat is not dependent on its C-terminal sequence, and suggests a role for endothelin-1 in the regulation of airway calibre. PMID- 1936224 TI - Lack of effect of dextromethorphan on breathlessness and exercise performance in patients with chronic obstructive pulmonary disease (COPD). AB - We have previously shown that the exercise performance of patients with severe chronic obstructive pulmonary disease (COPD) can be increased with the administration of oral morphine (0.8 mg.kg-1). The purpose of this study was to determine whether the administration of dextromethorphan (DXT), an antitussive structurally similar to codeine, would result in increased exercise performance and decreased dyspnoea in patients with COPD, without the side-effects of opiates. Six eucapnic patients (mean age = 66 +/- 3.8 yrs) with COPD (mean forced expiratory volume in one second (FEV1) = 1.01 +/- 0.07 l) underwent two incremental cycle ergometer tests to exhaustion (Emax) and assessment of their hypercapnic and hypoxic ventilatory responses and mouth occlusion pressure responses following first the oral administration of placebo (P) and then dextromethorphan (60 mg) in a single-blind fashion. There was no statistically significant difference in the maximal exercise performance, perceived dyspnoea (modified Borg scale), breathing pattern or expired gases after the two different treatments. In addition, the ventilatory response to CO2 production during exercise (delta VE/VCO2) and the ventilatory and mouth occlusion pressure responses to hypoxia and hypercapnia did not differ significantly after DXT as compared with after P. Indeed the exercise performance was poorer and the ventilatory responses were brisker after DXT. We conclude from this study that the administration of this opiate analogue does not improve the exercise capacity or decrease the ventilatory response of patients with COPD. PMID- 1936225 TI - Neutrophil function in chronic bronchitis. AB - This study was initiated with the question: Do defects in neutrophil functions predispose patients with chronic bronchitis to their recurrent bacterial infections? Forty five patients with chronic bronchitis and recurrent bacterial infections were studied. A number of aspects of neutrophil functions reflecting migratory and phagocytic functions and oxidative metabolism were measured in vitro, once in all 45 patients and 3 times in 22 patients over a period of 6 months. A great number of abnormalities was found on the first occasion with a complete normalization for all variables except one at the end of the observation period. The number of infectious exacerbations was significantly higher (p less than 0.05) at the start of the observation period i.e. October-November, as compared to the end, i.e. April-May. The oxidative metabolism, as reflected by lucigenin-enhanced chemiluminescence, was significantly reduced (p less than 0.001) also at the period of few infections, suggesting a primary defect of the neutrophil. Smoking was shown to adversely affect luminol-enhanced chemiluminescence and the chemokinetic activity of the patients' cells. We conclude that most variables were altered in a way which was anticipated from the study of individuals with acute bacterial infections. The probable primary defect in oxidative metabolism of the neutrophils in addition to the acquired defects as a consequence of smoking may add to the predisposition of some individuals to their recurrent bacterial infections. PMID- 1936226 TI - Plasma levels and effects of salbutamol after inhaled or i.v. administration in stable asthma. AB - The response and plasma levels of inhaled (0.15 mg.kg-1) and intravenous salbutamol (5 micrograms.kg-1) were studied in 12 patients who had previously been included in a study of acute severe asthma and were now in a stable phase. The maximal value for change (delta) in plasma salbutamol compared with the pretreatment value was higher after i.v. than after inhalation treatment (59 vs 30 nmol.l-1) but the areas under the curve (AUC) during 90 mins after treatment were similar for the two administration routes. The inter-individual differences in peak plasma salbutamol and AUC for delta plasma salbutamol were much greater after inhalation than after i.v. infusion. Immediately after treatment there was a greater increase in pulse rate (mean +17 vs +6 beats.min) and lower serum potassium level (mean -0.3 mmol.l-1) after i.v. than after inhalation treatment. The increase in peak expiratory flow (PEF) measured 90 min after the start of treatment (85 vs 31 l.min-1) and as AUC was significantly higher after inhalation than after i.v. treatment. Six patients had received i.v. treatment in the acute asthma study: in these patients delta PEF immediately after i.v. treatment was significantly lower in the stable situation (+49 vs +115 l.min-1). There was also a significant difference in the effect on the pulse rate immediately after i.v. treatment, with a decrease in the acute asthma and an increase in the stable asthma situation (-5 vs +16 beats.min-1). PMID- 1936227 TI - Effects of PEEP on respiratory mechanics in patients with COPD on mechanical ventilation. AB - We studied the effects of positive end-expiratory pressure (PEEP) applied by the ventilator on respiratory mechanics in ventilated patients with chronic obstructive pulmonary disease (COPD). Airway pressures, relaxed expiratory flow volume curves and end-expiratory volumes (EEV) were measured. In all patients investigated without PEEP applied by the ventilator, an intrinsic PEEP level (PEEPi) and a concavity in the flow-volume curve was present. Ventilator-PEEP caused a significant decrease in PEEPi in all patients (p less than 0.01). In patients in whom ventilator-PEEP exceeded PEEPi, significant increases occurred in airway pressures and EEV (p less than 0.05) and moreover the shape of the flow volume curve was changing. In patients in whom the level of ventilator-PEEP was below the PEEPi level, no significant changes in airway pressures, EEV or flow volume curves were found. We conclude: 1) PEEP applied by the ventilator can reduce PEEPi in ventilated patients with COPD without significant changes in airway pressures, EEV or flow-volume curves. 2) Expiratory flow-volume curves can be used to estimate the effects of ventilator-PEEP on EEV. PMID- 1936228 TI - Airway cooling: stimulus specific modulation of airway responsiveness in the canine lung periphery. AB - We used a wedged bronchoscope technique in conjunction with an in situ isolated perfused left lower lobe preparation in anesthetized dogs to examine cold associated airway modulation of peripheral lung responses to dry airflow, hypocapnia, and aerosols of histamine and hypertonic NaCl. In this preparation, airway wall temperature was rapidly lowered by decreasing the temperature of blood perfusing the wedged sublobar segment. Cooling significantly attenuated responses to dry air, hypertonic NaCl aerosol, and hypocapnic challenge. In contrast, cooling did not affect peripheral lung responses to aerosolized histamine. Thus, cooling per se does not inhibit the responsiveness of smooth muscle. We conclude that, depending on the stimulus, cooling can modulate airway reactivity. We speculate that cooling attenuates hypocapnia, hypertonic aerosol, and dry air-induced bronchospasm via a cold induced reduction in neuronal activity or mediator production and release. PMID- 1936229 TI - Effects of home environment on respiratory symptoms and lung function in a general population sample in north Italy. AB - Effects of indoor pollution exposure were evaluated in a general population sample (n = 3,289) living in the Po River Delta area. Prevalence rates of chronic cough in men and dyspnoea in women were significantly higher in association with the use of bottled gas (propane) for cooking instead of natural gas (methane). Chronic cough and phlegm in men and dyspnoea in women were significantly associated with the use of a stove for heating. When combining type of heating and fuel used, in men a trend toward higher prevalence rates of chronic cough and phlegm was shown in those with stove or fan heating (regardless of the fuel); in women the trend reached statistical significance for dyspnoea. The relationship between stove (regardless of fuel) and decrease in forced expirograms was statistically significant only in women. In multiple logistic models, accounting for independent effects of age, smoking, pack-years, parents' smoking, socio economic status, body mass index, significantly increased odds ratios were found in males for the associations of: bottled gas for cooking with cough (1.66) and dyspnoea (1.81); stove for heating with cough (1.44) and phlegm (1.39); stove fuelled by natural gas and fan or stove fuelled other than by natural gas with cough (1.54 and 1.66). In females, significantly increased odds ratios were found only for dyspnoea when associated with bottled gas for cooking (1.45), stove for heating (1.46), stove fuelled by natural gas (1.58), stove or fan fuelled other than by natural gas (1.73).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936230 TI - Human respiratory muscles: fibre morphology and capillary supply. AB - In man the diaphragm (DIA) and abdominal muscles comprise approximately 50% slow twitch (ST) fibres, whereas a higher proportion (60%) is found in intercostal muscles and the scalenes. All respiratory muscles show an equal distribution of fast-twitch (FTa and b) fibres with the exception of the expiratory intercostal muscles which have few FTb fibres. The inspiratory muscles have a uniformly small fibre size, in contrast to the expiratory intercostal muscle fibres which are large. The fibre size of the inspiratory muscles is maintained with ageing, whereas that of the expiratory intercostal muscles appears to be reduced after the age of 50 yrs. Capillary supply is most abundant in the expiratory muscles followed by DIA and the inspiratory intercostal muscles. In patients with chronic obstructive pulmonary disease (COPD) it is unknown whether a reduction in fibre size of the thoracic respiratory muscles is caused by extreme use due to increased ventilatory work, or by disuse due to an increased involvement of the extrathoracic respiratory muscles. Histochemical characteristics suggest that, in normal humans, the load on the inspiratory muscles is relatively small during contractions, whereas the expiratory intercostal muscles are exposed to severe continuous activity with a heavy load. PMID- 1936232 TI - Accuracy, precision and linearity of the portable flow-volume meter Microspiro HI 298. AB - The accuracy, precision and linearity of a new portable flow-volume meter, the Microspiro HI-298 (Chest Corporation, Tokyo, Japan), was investigated using a Fleisch no. 4 pneumotachograph as a standard. After connection and calibration of the pneumotachograph and the Microspiro, a healthy subject performed 44 forced vital capacity (FVC) manoeuvres at different levels of lung inflation. The FVC of these expirations ranged from 2.5-5.1 l. Linear regression of Microspiro values (dependent variable) on Fleisch pneumotachograph values (independent variable) showed that a good linear relationship existed: Pearson correlation coefficients ranged from 0.938-0.985. Linearity of the Microspiro was good except for the peak expiratory flow rate (PEFR) and the maximal expiratory flow at 25% of the expired volume (MEF75). The random error (measure of precision) of all flow-volume (F-V) indices was lower than 5%. The systematic error (measure of accuracy) was low for the forced expiratory volume in one second (FEV1) and the FVC (1% and 4.6%, respectively) but much higher for the instantaneous expiratory flows (PEFR 11.0%; MEF75 7.0%; MEF50 8.5%; MEF25 11.4%). Only the total error in FEV1 complied with the tolerance of 4% of the European Community for Coal and Steel (ECCS). When the measured values were adjusted according to the regression equations of this study, all F-V indices were accurate and precise within 5%. It was concluded that the portable Microspiro HI-298 is a useful instrument for bedside, work-site spirometry and for use in general practice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936231 TI - The acoustic reflection technique for non-invasive assessment of upper airway area. AB - Non-invasive assessment of upper airway area by acoustic reflections has been developed in the last 12 yrs. The technique is based on the analysis of sound waves reflected from the airways. Measurement of the amplitudes of the reflections and their times of arrival at the sensing microphone permits construction of a plot of airway area vs distance from the microphone. We describe the theoretical foundations of the method and review the underlying assumptions. This is followed by a summary of the results of in vitro and in vivo validation studies, with particular attention to the reproducibility, accuracy and variability of the technique. The description of clinical and physiological applications of this technique includes detection of tracheal stenosis, demonstration of structural and functional abnormalities of the pharynx and glottis in patients with sleep apnoea, dichotomous response of the airway area to exercise, and airway vs parenchymal hysteresis. Finally, we comment on the future directions that might be investigated using this technique. PMID- 1936233 TI - Which apparatus for inhaled pentamidine? A comparison of pulmonary deposition via eight nebulisers. AB - Aerosolised pentamidine 300 mg in 5 or 6 ml solution was administered via 8 different nebuliser systems to 12 patients with acquired immunodeficiency syndrome. Using 99mTc human serum albumin as an indirect marker for pentamidine, pulmonary, extrapulmonary (gastric and oropharyngeal) and alveolar deposition of pentamidine were measured using a gamma camera. Side effects (visual analogue scales) and changes in lung function associated with each treatment were also quantified. Deposition was completed more rapidly with the ultrasonic than the jet nebulisers. Mean total pulmonary depositions (mg +/- SEM) were Respirgard II, 6.1 +/- 0.5; Centimist, 7.3 +/- 1.0, System 22 Mizer, 14.3 +/- 2.1; System 22 Mizer with particle separator; 4.5 +/- 0.4; System 22 Mizer with Optimist 2, 6.3 +/- 0.9; Fisoneb, 6.0 +/- 1.2; Pentasonic (Portasonic); 4.6 +/- 0.9; Samsonic, 2.9 +/- 0.4. Differences between the nebulisers for peripheral lung and alveolar deposition reflected this pattern. Side effects scores were largest with System 22 Mizer, Pentasonic (Portasonic), and Fisoneb, and these produced the greatest oropharyngeal and gastric deposition. The largest reductions in lung function were associated with System 22 Mizer. A 300 mg dose of pentamidine nebulised via Respirgard II is known to be effective prophylaxis for Pneumocystis carinii pneumonia when given once monthly. Our results show that equivalent pulmonary deposition can be produced by other nebulisers. System 22 Mizer gives over twice the deposition associated with Respirgard II, and used with a pentamidine dose of 150 mg is likely to produce an adequate lung dose for prophylaxis. This nebuliser, however, is associated with more marked side effects. PMID- 1936235 TI - Spherocytosis and pulmonary hypertension coincidental occurrence or causal relationship? AB - A report is given on a 59 yr old man with hereditary spherocytosis and progressive shortness of breath on exertion, due to severe pulmonary hypertension and cor pulmonale. An open lung biopsy was performed in order to exclude all known aetiologies of secondary pulmonary hypertension. Pathological examination revealed in situ thrombosis and asymmetric fibromuscular hyperplasia of small- and medium-sized pulmonary arteries. Both primary pulmonary hypertension and hereditary spherocytosis have a low incidence in the general population and their simultaneous occurrence has not been reported previously; the possibility that this was due to a causal relationship and not to coincidence cannot be ruled out, in view of some similarities with pulmonary hypertension complicating sickle cell anaemia. PMID- 1936236 TI - Okadaic acid stimulates carnitine palmitoyltransferase I activity and palmitate oxidation in isolated rat hepatocytes. AB - Okadaic acid parallely increased carnitine [corrected] palmitoyltransferase I activity and the rate of palmitate oxidation in isolated rat hepatocytes. Nevertheless, okadaic acid had no significant effect on the rate of octanoate oxidation. Maximal effects of okadaic acid were similar and non-additive to those of dibutyryl-cAMP, forskolin and glucagon. Results indicate that carnitine palmitoyltransferase I activity may be controlled by a mechanism of phosphorylation/dephosphorylation. PMID- 1936237 TI - Syringopeptins, new phytotoxic lipodepsipeptides of Pseudomonas syringae pv. syringae. AB - The primary structure of some new lipodepsipeptides named syringopeptins, produced by plant pathogenic strains of Pseudomonas syringae pv. syringae has been determined by a combination of chemical methods, 1H and 13C NMR spectroscopy and FAB mass spectrometry. Two syringomycin-producing strains afforded 3 hydroxydecanoyl-Dhb-Pro-Val-Val-Ala-Ala-Val-Val-Dhb-Ala-Val-Ala- Ala-Dhb-aThr-Ser Ala-Dhb-Ala-Dab-Dab-Tyr, with Tyr acylating a Thr to form a macrolactone ring, and smaller amounts of the 3-hydroxydodecanoyl homologue. Evidence was obtained that a third syringomycin-producing strain and a syringotoxin-producing strain synthesize 3-hydroxydecanoyl-Dhb-Pro-Val-Ala-Ala-Val-Leu-Ala-Ala-Dhb-Val-Dhb- Ala Val-Ala-Ala-Dhb-aThr-Ser-Ala-Val-Ala-Dab-Dab-Tyr, with Tyr and aThr forming again the macrolactone ring, and smaller amounts of the 3-hydroxydodecanoyl homologue. PMID- 1936234 TI - A flow interruption device for measurement of airway resistance. AB - Unlike conventional methods, the interrupter method for measuring airway resistance is non-invasive and requires minimal patient co-operation. It can therefore be applied in critically ill patients, acute asthmatics, neonates, pre school children, geriatric patients and unconscious patients. The method is based on transient interruption of airflow at the mouth for a brief period during which alveolar pressure equilibrates with mouth pressure. Measurement of mouth pressure is used to estimate alveolar pressure prior to interruption and the ratio of this to flow prior to interruption gives airway resistance. Using the interrupter method we have developed a portable device for measuring airway resistance which is simple to use and gives a direct instantaneous reading. Measurements of airway resistance obtained using the new device were compared with those obtained using conventional body plethysmograph methods in 43 adult patients. A close correlation was seen (r = 0.86). The two methods appear equally sensitive in detecting changes in airway resistance following bronchodilator therapy. The device has been used successfully in pre-school children unable to co-operate with conventional methods. PMID- 1936238 TI - Phytochrome control and anoxia effect on the activity and expression of soybean seedling lipoxygenases 1 and 2. AB - The effects of different light irradiations and anoxia treatment on the activity and expression of the lipoxygenases 1 (LOX-1) and 2 (LOX-2) of soybean seedlings have been investigated. A phytochrome-mediated decrease of the specific activities of both isoenzymes was found which was due to the regulation of the gene expression at the transcriptional level. The anoxia treatment of the seedlings led to a decrease of both lipoxygenase specific activities as well, but this effect was attributable to the reduction of the amount of the two isoenzymes, without changes in the steady-state levels of specific mRNAs. Therefore, light and anoxia are both regulators of soybean lipoxygenases, but their mechanism of action at the molecular level is different. PMID- 1936239 TI - Association of a 24-kDa GTP-binding protein, Gn24, with human platelet alpha granule membranes. AB - Human platelets were disrupted using nitrogen cavitation and fractionated on sucrose density gradients to permit isolation of alpha-granules, the major secretory granule of platelets. Membrane proteins prepared from intact alpha granules by alkali extraction were separated by SDS-polyacrylamide gel electrophoresis, transferred to nitrocellulose and the blot probed for the presence of GTP-binding proteins using [alpha-32P]GTP. Two low molecular mass GTP binding proteins with molecular mass of 27 and 24 kDa, respectively, were identified on the alpha-granule membrane. In contrast to the 27-kDa protein which was present in significant amounts in the plasma membrane-enriched fraction, the 24-kDa protein showed a preferential association with the alpha-granule membrane. On immunoblotting with specific antiserum, the 24-kDa GTP-binding protein was found to be distinct from rab3A. To the best of our knowledge, the present report represents the first identification of low molecular mass GTP-binding proteins associated with a platelet secretory granule. PMID- 1936240 TI - Two antifungal thaumatin-like proteins from barley grain. AB - Antifungal activity has been associated with 2 immunochemically distinct proteins, protein R and S (Mr approximately 23 kDa; pI 9-10), which were isolated in pure form from barley grain. The proteins are homologous with thaumatin- and pathogenesis-related proteins of the PR5 family. The proteins inhibit growth of i.a. Trichoderma viride and Candida albicans in microtiter plate assays and act synergistically with barley grain chitinase C. Like maize zeamatin, protein R and S but not chitinase C retarded fungal growth in synergism with nikkomycin Z, a nucleoside-peptide inhibitor of fungal chitin synthesis. Although no inhibition of alpha-amylases or serine proteases could be associated with protein R or S the results indicate that the homologous maize grain bifunctional inhibitor of insect alpha-amylase and trypsin is very similar to or identical with maize zeamatin, which was proposed to have permeabilizing activity towards fungal membranes. Thus, in addition to the intensely sweet properties of thaumatin, multiple unrelated defense functions against insect and fungal pests can now be associated with the family of thaumatin-homologous proteins. PMID- 1936241 TI - Reconstitution of the solubilized cardiac sarcoplasmic reticulum potassium channel. Identification of a putative Mr approximately 80 kDa polypeptide constituent. AB - Recent evidence has indicated that potassium ion movement through sarcoplasmic reticulum (SR) K+ channels is an important countercurrent for Ca2+ release from SR. We used Chaps-solubilized SR vesicles and sucrose density gradient centrifugation to identify components of the canine cardiac SR K+ channel. To overcome the difficulty of the absence of a high-affinity specific ligand, we have successfully applied the planar lipid bilayer reconstitution technique to identify and functionally assay for the solubilized SR K+ channel. We found that Chaps solubilization of the channel did not change the protein's functional properties. The cardiac SR K+ channel sediments as a 15-20S protein complex. A polypeptide of Mr approximately 80 kDa was found to specifically comigrate with the 15-20S gradient fractions and might be a major constituent of the cardiac SR K+ channel. PMID- 1936242 TI - cDNA cloning of a human androgen-induced mRNA exhibiting an early and protein synthesis-independent induction. AB - The detailed mechanism of action of androgens remains unknown. We have used an androgen-dependent human prostate cancer cell line and a subtractive cDNA hybridisation strategy to enrich for androgen-dependent sequences. This yielded a cDNA clone which exhibits the characteristics of a primary trans-activated target for androgens. This androgen-regulated gene encodes a polyadenylated 4.5 kb mRNA which is induced 30-50-fold within 3 h of treatment with 10 nM dihydrotestosterone. The induction does not require continued protein synthesis as it is maintained in the presence of protein synthesis inhibitors. PMID- 1936243 TI - A new class of anti-HIV agents: GAP31, DAPs 30 and 32. AB - Three inhibitors of human immunodeficiency virus (HIV) have been isolated and purified to homogeneity from Euphorbiaceae himalaya seeds (Gelonium multiflorum) and carnation leaves (Dianthus caryophyllus). These proteins, GAP 31 (Gelonium Anti-HIV Protein 31 kDa) and DAPs 30 and 32 (dianthus anti-HIV proteins, 30 and 32 kDa), inhibit HIV-1 infection and replication in a dose-dependent manner with little toxicity to target cells. The therapeutic indices of these compounds are in the order 10(4), suggesting that they may be clinically important agents in the treatment of AIDS. The N-terminal amino acid sequences of these proteins show little homology to those of previously described anti-HIV proteins. The structure function features of these HIV inhibitors, based on the 40-60 amino acid residues of N-terminal sequences, are examined. PMID- 1936244 TI - Comment: di(1,N6-ethenoadenosine)-5',5'''-P1,P4-tetraphosphate, a fluorescent enzymatically active derivative of Ap4A. PMID- 1936245 TI - Calponin. Developmental isoforms and a low molecular weight variant. AB - Two-dimensional gel analysis of basic proteins in developing human smooth muscle identifies calponin as a prominent marker of the differentiated phenotype. Adult tissue (human and mouse) typically expresses up to four calponin isoforms, three of which appear sequentially during fetal development: adult myometrial cells express the same three isoforms in primary culture in vitro and these are down regulated, in reverse order, during the subsequent modulation of phenotype. Monospecific, polyclonal antibodies against calponin identify a lower molecular weight variant of calponin (L-calponin) that is strongly and specifically expressed in adult smooth muscles of the human urogenital tract. L-calponin is down-regulated in benign smooth muscle derived tumors (leiomyoma) and is not expressed in primary cultures of normal uterine tissue. PMID- 1936246 TI - Use of a monoclonal antibody (APE-1) directed against the conserved GTPEYLAPE motif present in protein kinases as an affinity purification reagent. AB - cDNA sequence studies have predicted the existence of protein kinases that have not been characterized at the protein level. This laboratory has previously shown that polyclonal rabbit antibodies directed against a highly conserved sequence motif, GTPEYLAPE, present in the catalytic domain of many protein kinases will react during immunoblots with several protein kinases containing the same or homologous motifs. In this report I describe the development of a mouse monoclonal antibody, designated APE-1, that reacts with the GTPEYLAPE motif. In addition, the use of this monoclonal antibody in the affinity purification of kinase activities from rabbit reticulocyte lysate is described. This approach may provide a general method for the purification of previously uncharacterized protein kinases that share regions which are homologous to the GTPEYLAPE motif. Refinements in this method may permit the rapid purification of nonabundant and/or rapidly inactivated protein kinases that have not been isolated using other approaches. PMID- 1936247 TI - The amino acid sequence of AQN-3, a carbohydrate-binding protein isolated from boar sperm. Location of disulphide bridges. AB - Gamete recognition and adhesion are essential steps in fertilization. Among others, carbohydrate-binding proteins on the sperm surface have been recognized to play a central role in the initial interaction of the male gamete with components of the zona pellucida of the homologous investing oocyte. We have isolated several members of a carbohydrate- and zona pellucida-binding protein family from ejaculated sperm. Here we report the biological origin and structural characterization of AQN-3, a component of this carbohydrate-binding family. The molecular weight of purified AQN-3 was determined by plasma desorption mass spectrometry. The protein was chemically and enzymatically degraded, the proteolytic fragments isolated and characterized by N-terminal sequencing and fast atom bombardment mass spectrometry. In this manner we established the complete amino acid sequence of AQN-3 and the location of its two disulphide bonds. No analogous protein sequence could be found in the MIPS protein sequence data bank, indicating that AQN-3 may belong to a novel mammalian carbohydrate binding protein family. PMID- 1936248 TI - Cloning and sequence analysis of pituitary cDNA encoding the beta-subunit of Xenopus proteasome. AB - The proteasome is a multicatalytic proteinase composed of a number of non identical subunits. A Xenopus pituitary cDNA was isolated and found to code for the beta-subunit of proteasome. The amino acid sequence deduced from the open reading frame consisted of 215 amino acid residues with a calculated molecular weight of 23,979. A comparative structural analysis indicated that the proteasome subunits can be divided into two groups with the same evolutionary origin. One group consists of subunits with an N-terminally blocked residue and includes components C2, C3, C8 and C9, while the second group of non-blocked proteins includes component C5 and the beta-subunit. PMID- 1936249 TI - Evidence for a NO-rebound mechanism for production of N2O from nitrite by the copper-containing nitrite reductase from Achromobacter cycloclastes. AB - Reduction of NO2- by the Cu-containing nitrite reductase from Achromobacter cycloclastes produces NO as the primary product initially, but as NO accumulates, NO production levels-off and N2O production becomes significant. Reaction of the enzyme with NO2- in the presence of NO increases the amount of N2O product significantly, while trapping the NO product as nitrosylhemoglobin or rapid removal of NO by sparging results in no detectable N2O production. Reaction of the enzyme with 15NO2- in the presence of 14NO results in rapid formation of the mixed isotope product (14N, 15N)O in ca. 45% yield. In contrast, the presence or absence of NO has no effect on N2O production by a prototypical heme cd1 containing nitrite reductase. These results are consistent with formation of a labile Cu(+)-NO+ species in the copper enzyme, which normally decomposes to NO. Production of N2O requires that the released NO must rebind to the enzyme to combine with a second NO2- or a species derived therefrom. PMID- 1936250 TI - Structural and functional analysis of Trichoderma reesei endoglucanase I expressed in yeast Saccharomyces cerevisiae. AB - The function of the domains of Trichoderma reesei endoglucanase I (EGI) has been studied. Truncated EGI proteins were expressed from the 3'-end deleted cDNAs in the yeast Saccharomyces cerevisiae under the control of the ADC1 expression cassette. EGI protein was detected by monoclonal antibody EI-2 and EGI activity as cleared zones around growing colonies on agar plates containing hydroxyethylcellulose (HEC) covalently stained with Ostazin brilliant red (OBR). The results showed that the The-Ser-rich hinge region and the conserved 'tail' are not necessary for the efficient synthesis and secretion of EGI in yeast, but the intact core region is necessary for the enzymatic activity. PMID- 1936251 TI - Remarkably enhanced expression of the type II hexokinase in rat hepatoma cell line AH130. AB - Expression of mRNAs encoding hexokinase isozymes was studied in various cells such as rat brain, liver, skeletal muscle, kidney and heart, and the rat hepatoma cell line AH130 by Northern blotting. High specific expression of type II hexokinase was observed only with AH130 cells. In contrast, specific expression of type I hexokinase was detected in energy-requiring normal tissue cells such as brain and heart. These results suggest that the expression of hexokinase isozyme in the tumor cells is different from that in normal cells. PMID- 1936252 TI - Sphingosine and unsaturated fatty acids modulate the base exchange enzyme activities of rat brain membranes. AB - The base exchange enzymes catalyze the incorporation of L-serine, ethanolamine and choline into their corresponding phospholipids. The L-serine base enzyme activity was increased 120% by 0.1 mM sphingosine. There was a modest increase of the ethanolamine base exchange enzyme activity but the choline base exchange enzyme activity was unaffected. Na-arachadonate, Na-oleate and Na-linolenate at 0.2 mM concentration increased the activity of the L-serine and ethanolamine base exchange enzymes but inhibited the choline base exchange enzyme activity. A model is proposed suggesting that modulations of the L-serine base exchange enzyme may participate in the regulation of the calcium phospholipid-dependent protein kinase C. PMID- 1936253 TI - Acidic pentapeptide phosphorylated in vitro by calf thymus protein kinase NII binds to DNA in the presence of Mg2+ cations. AB - The pentapeptide pyroGlu-Ala-Glu-Ser-Asn has been synthetized and phosphorylated in vitro at level of serine by protein kinase NII isolated from calf thymus chromatin. It is noteworthy that the calf thymus kinase NII shows a remarkable affinity for this peptide. The [32P]peptide is able to bind to several DNAs in the presence of Mg2+ (lambda phage, calf thymus, pBR540 plasmid). This binding appears not specific with regard to the type of DNA and its base sequence. These data support the hypothesis that phosphorylated acidic domains of nuclear nonhistone proteins could bind directly to DNA in the presence of Mg2+ cations. PMID- 1936255 TI - Respiratory burst inhibition in human neutrophils by ultra-low doses of [D Ala2]methionine enkephalinamide. AB - An ultra-low dose (10(-14) M) of opioid peptide [D-Ala2]methionine enkephalinamide (DAMEA) is found to exert an inhibitory effect on the production of reactive oxygen species (respiratory burst) in human neutrophils. The validity of this phenomenon has been verified in a series of studies that comprised 30 experiments. The inhibition has proved to be statistically significant (P less than 0.001). The dose-response dependence of the effect (10(-15)-10(-9) M) followed a characteristic biphasic pattern (with the maximum effect at ultra-low doses). An opioid antagonist, naloxone partially blocks the inhibitory effect, which indicates that the DAMEA action is at least partially mediated by opioid receptors. PMID- 1936254 TI - Molecular cloning and primary structure of Thermoactinomyces vulgaris carboxypeptidase T. A metalloenzyme endowed with dual substrate specificity. AB - A gene coding for an extracellular Zn-carboxypeptidase of Thermoactinomyces vulgaris has been cloned and sequenced (EMBL X56901). This enzyme named carboxypeptidase T reveals simultaneously both types of substrate specificity characteristic of mammalian carboxypeptidases A and B. The carboxypeptidase T gene is primarily expressed in E. coli as a non-active preproenzyme with an additional 98 amino acid residues at the N-terminus. Primary structure alignment of mature carboxypeptidase T and mammalian metallocarboxypeptidases demonstrated 25-30% overall identity but a full preservation of presumed catalytically important residues. These observations imply a basic uniformity of the general catalytic mechanism for enzymes of that class produced by evolutionarily remote organisms. PMID- 1936256 TI - Possible involvement of GTP-binding proteins in growth regulation of human epidermoid carcinoma cell line A431. AB - A431 cells, a human epidermoid carcinoma cell line, express an unusually large number of cell surface receptors for the epidermal growth factor (EGF). The growth rate of A431 cells was estimated by measuring [3H]thymidine incorporation at the logarithmic growth phase. The growth of the cells in protein-free medium was partially inhibited by exposure of the cells to pertussis toxin, islet activating protein (IAP). The growth in both serum-containing and protein-free medium was inhibited by high concentrations of EGF, and these inhibitions were partially reversed by treatment of the cells with IAP. The effects of IAP were well correlated with the degree of ADP-ribosylation of a membrane 40-kDa protein. Thus, IAP sensitive G-proteins appear to be involved in the signal transduction of both positive and negative regulation of A431 cell growth. The possibility is also discussed that phosphatidylinositol turnover may participate in growth regulation. PMID- 1936257 TI - POMC gene expression in mouse and hamster melanoma cells. AB - Expression of mRNA hybridizable to murine POMC cDNA, and immunoreactivity specific for POMC derived peptide, beta-endorphin, are reported for the first time in one murine and two hamster melanoma lines. The apparent sizes of POMC mRNA transcript were 3.5, 1.5 and 1 kb. It is suggested that POMC gene expression may be involved in the autoregulation of the melanoma phenotype at the cellular and tissue levels. PMID- 1936258 TI - Effects of lonidamine on the membrane electrical properties of Ehrlich ascites tumor cells. AB - The effects of lonidamine on membrane electrical properties of Ehrlich ascites tumor cells are investigated. Using a dielectric relaxation technique based on the Maxwell-Wagner effect and elaborated by a 'single-shell' fitting procedure, the data indicate that both membrane conductivity and membrane permittivity increase after treatment of these cells with lonidamine while the conductivity of the cytosol remains unchanged. Changes in membrane proteins and/or lipids are suggested which lead to altered membrane structure and/or function. PMID- 1936260 TI - Posttranscriptional regulation of c-myc RNA during early development of Xenopus laevis. AB - The remarkable stability of c-myc during oogenesis contrasts with its degradation during the early developmental period in Xenopus laevis. Three evolutionary conserved motifs found in the 3'-untranslated region of Xenopus c-myc RNAs have been analyzed for a possible role in c-myc RNA degradation. No specific degradation was observed when these sequences were cloned downstream of a reporter gene and the corresponding RNAs were injected into fertilized eggs. The relation between polyadenylation and degradation of c-myc mRNA has been examined during early development. c-myc is adenylated during early oogenesis, and a dramatic de-adenylation occurs in full grown oocytes. Consequently, the de adenylation of c-myc mRNA that occurs in eggs might be a requirement for its degradation after fertilization, but is not sufficient to trigger its degradation. PMID- 1936259 TI - Cytotoxicity of, and DNA damage by, active oxygen species produced by xanthine oxidase. AB - Toxicity to Raji cells of the xanthine oxidase/hypoxanthine system is related to the formation of single-strand DNA breaks. DNA damage was proportional to the concentration of xanthine oxidase and to the time of exposure. It was prevented by the absence of hypoxanthine, or by the presence of allopurinol, or both superoxide dismutase and catalase. The release of 51Cr from damaged cells was detectable 12 h after the inhibition of cloning efficiency and the production of DNA breakage. These data suggest that DNA damage induced by the oxygen products precedes the severe lesion to the cellular membrane. PMID- 1936261 TI - Interleukin-4 inhibits the differentiation of mouse myeloid leukemia M1 cells induced by dexamethasone, D-factor/leukemia inhibitory factor and interleukin-6, but not by 1 alpha,25-dihydroxyvitamin D3. AB - The effects of interleukin-4(IL-4) on the growth and differentiation of mouse myeloid leukemia M1 cells induced by various differentiation inducers were investigated. IL-4 alone did not have any significant effect on the growth or differentiation of M1 cells, but inhibited their differentiation induced by dexamethasone, D-factor/leukemia inhibitory factor, or interleukin 6. IL-4 also restored the proliferation of M1 cells after growth inhibition during their induction of differentiation by inducers. In contrast, IL-4 enhanced inhibition of growth and induction of differentiation of M1 cells by 1 alpha,25 dihydroxyvitamin D3. These results indicate that modulation of differentiation of M1 cells by IL-4 depends on the differentiation inducer. PMID- 1936262 TI - Interaction of the duplicated segment carried by Clostridium thermocellum cellulases with cellulosome components. AB - The function of the non-catalytic, duplicated segment found in C. thermocellum cellulases was investigated. Rabbit antibodies reacting with the duplicated segment of endoglucanase CelD cross-reacted with a variety of cellulosome components ranging between 50 and 100 kDa. 125I-labeled forms of CelD and of xylanase XynZ carrying the duplicated segment bound to a set of cellulosome proteins ranging between 66 and 250 kDa, particularly to the 250 kDa SL (or S1) subunit. 125I-labeled forms of CelD and XynZ devoid of the duplicated segment failed to bind to any cellulosome protein. The duplicated segment appears thus to serve to anchor the various cellulosome subunits to the complex by binding to SL, which may be a scaffolding element of the cellulosome. PMID- 1936263 TI - Isolation of mitotic p34cdc2 apoenzyme from human cells. AB - A simple procedure was devised for isolating from homogenates of mitotic cells the human homolog to the fission yeast cdc2 gene product. The identity of the purified protein was established with anti-p34cdc2 antibodies and p13suc 1, both specific ligands for p34cdc2. Active-site labeling with oxidized [alpha 32P]ATP showed the purified molecule to be an ATP-binding protein. Its ability to phosphorylate casein but not histone, and its phosphorylation on tyrosine, detected by anti-phosphotyrosine antibodies, indicates the form of p34cdc2 purified is the inactive or apoenzyme form. Purified quantities of human p34cdc2 should be of considerable value in establishing the mechanism of its activation at mitosis by phosphatases. PMID- 1936264 TI - 8-37h-CGRP antagonizes actions of amylin on carbohydrate metabolism in vitro and in vivo. AB - 8-37hCGRP is a potent antagonist at calcitonin gene-related peptide (CGRP) liver membrane receptors; it also blocks vasodilator actions of CGRP and the related peptide, amylin, in intact rats. We now report that 8-37hCGRP antagonizes amylin inhibition of insulin-stimulated labelled glucose uptake into isolated rat soleus muscle, and inhibits amylin-evoked elevation of plasma lactate and glucose in fasted anaesthetized rats. The different relative potencies of the 3 ligands (amylin, CGRP, 8-37hCGRP) on the liver receptor and on the soleus muscle point to distinct CGRP receptors in liver membranes and amylin receptors on muscle cells. PMID- 1936265 TI - Antiviral activity of some natural and synthetic sugar analogues. AB - A number of natural and synthetic sugar analogues have been tested for their antiviral activity, using an influenza virus strain as a model. Hemagglutinating titres (HA) and cytopathic effect (CPE) were surveyed to estimate the virus production. It was found that introduction of the benzyl group into these sugars generally causes them to become antivirally active. Substitution with methyl, acetyl, uridyl and thiocyanyl groups or derivatization with azido, isopropylidene and benzylidene groups were without effect. All sugars containing the 2-deoxy-2 acetamido group were inactive. PMID- 1936266 TI - Mitogenic signal transduction in normal and transformed 32D hematopoietic cells. AB - We studied mitogenic signal transduction in normal and oncogene-transformed 32D cells, a murine hematopoietic cell line that is normally dependent on interleukin 3 (IL3) for proliferation and survival. The formation of second messengers was measured in normal cells stimulated with IL3, and in cells transfected with foreign growth factor receptor genes and stimulated with appropriate growth factors. We also measured the steady-state level of second messengers in 32D cells transformed by erbB, abl, and src oncogenes which abrogate growth factor requirement. We found that IL3 stimulated the formation of diacylglycerol independently of inositol lipid turnover, but concomitantly with increased turnover of phosphatidylcholine. Epidermal growth factor (EGF), and platelet derived growth factor (PDGF) stimulated the 'classical' turnover of inositol lipids with formation of diacylglycerol and calcium-mobilizing inositol phosphates. Colony stimulating factor-1 triggered inositol lipid turnover, although to a much lower extent than EGF and PDGF. Transformed cells showed elevated levels of diacylglycerol together with increased turnover of phosphoinositides and phosphatidylcholine. Taken together these results indicate that different growth factors and oncoproteins associate with multiple signalling pathways in 32D cells. PMID- 1936267 TI - Purification and subunit composition of a GTP-binding protein from maize root plasma membranes. AB - When frozen plasma membranes isolated from maize seedling roots are thawed, a significant portion of GTP-binding activity goes into solution. The GTP-binding protein was purified by ion exchange chromatography on Mono-Q and gel filtration on Superose 6. Its molecular weight was estimated at 61 kDa by gel filtration. The same molecular weight was obtained upon solubilization of the GTP-binding protein with cholic acid followed by gel filtration in the presence of this detergent. SDS-PAGE demonstrated that the isolated GTP-binding protein consists of two types of subunit of molecular weights 27 kDa and 34 kDa. PMID- 1936268 TI - Protein aggregation and inclusion body formation in Escherichia coli rpoH mutant defective in heat shock protein induction. AB - Mutations in the rpoH gene, encoding sigma 32, an alternative factor required for transcription of the heat shock genes, result in the extensive aggregation of virtually all cellular proteins and formation of inclusion bodies both under stress and non-stress conditions. Inhibitors of protein synthesis suppress this aggregation, suggesting that newly synthesized proteins preferentially aggregate in rpoH mutants. These data suggest that the heat shock proteins are involved in acquisition of the soluble state (i.e. correct conformation) of the bulk of intracellular proteins after their translation. PMID- 1936271 TI - PDGF suppresses the activation of group II phospholipase A2 gene expression by interleukin 1 and forskolin in mesangial cells. AB - Treatment of rat mesangial cells with interleukin 1 beta (IL-1 beta) and forskolin greatly enhanced the expression of group II phospholipase A2 (PLA2) mRNA, with subsequent increased synthesis and secretion of PLA2, as detected by PLA2 activity measurements and immunoprecipitation of culture media of [35S]methionine-labelled mesangial cells. PDGF-BB dose-dependently suppressed the IL-1 beta- and forskolin-induced elevation of PLA2 mRNA, as well as PLA2 synthesis and secretion. In contrast, PDGF-AA had no inhibitory effect. The tyrosine kinase inhibitor genistein dose-dependently antagonized the inhibitory effect of PDGF-BB on IL-1 beta-stimulated PLA2 secretion, thus suggesting that tyrosine phosphorylation may be required for PDGF-BB inhibition of PLA2 gene expression in mesangial cells. PMID- 1936269 TI - Acetylcholine interactions with tryptophan-184 of the alpha-subunit of the nicotinic acetylcholine receptor revealed by transferred nuclear Overhauser effect. AB - Acetylcholine interactions with three genetically engineered fusion proteins containing peptides from the nicotinic acetylcholine receptor were studied by 1D and 2D nuclear magnetic resonance methods. The three proteins were Torpedo alpha 184-200, Torpedo alpha 186-198, and human alpha 183-204 of the acetylcholine receptor fused to the first 323 residues of the E. coli protein trpE. Nuclear Overhauser effect studies revealed interactions of bound acetylcholine with tryptophan-184 present in the Torpedo alpha 184-200, and the human alpha 183-204 sequences. These interactions are between the N(CH3)3+ and CH3 groups of acetylcholine with the aromatic protons of tryptophan. The appearance of these cross-peaks indicates a distance of less than 5 A between tryptophan and the bound ligand; however, direct contact has yet to be proven. PMID- 1936270 TI - Molecular cloning and sequence analysis of cDNA and genomic DNA for the human cone transducin alpha subunit. AB - A novel GTP binding protein (G protein) alpha subunit cDNA was isolated from a T cell leukemia cell line, Jurkat, utilizing polymerase chain reaction (PCR). The predicted amino acid sequence of this G protein alpha subunit showed the highest identity (96.6%) to bovine cone cell-specific transducin (Tc alpha). The organization of the coding region of this G protein alpha subunit gene was composed of 8 exons and 7 introns. Northern hybridization revealed the presence of this G protein message in a retinoblastoma cell line, Y79. In Jurkat, however, the message was detectable only by reverse transcription/PCR. Taken together, this novel G protein alpha subunit must be human Tc. PMID- 1936272 TI - A coupled in vitro transcription-translation system for the exclusive synthesis of polypeptides expressed from the T7 promoter. AB - A coupled transcription-translation in vitro system has been developed in Escherichia coli specifically for the expression of genes under the exclusive control of the T7 promoter. This system consists of an E. coli crude extract (prepared from cells containing endogenous T7 RNA polymerase), rifampicin (an E. coli RNA polymerase inhibitor) and a labelled amino acid. When primed with a plasmid template encoding the target gene under exclusive control of the T7 promoter, this system has the capability to synthesize relatively large amounts of a unique, labelled polypeptide. This paper describes the characteristics and use of such a T7 RNA polymerase/T7-promoter specific in vitro system. PMID- 1936273 TI - Choleratoxin ADP-ribosylates transducin only when it is bound to photoexcited rhodopsin and depleted of its nucleotide. AB - The sensitivity of transducin (T) to choleratoxin (CT) in retinal cells depends on illumination and on the presence of GTP or analogs. Low concentrations of GPP NH-P or GPP-CH2-P increase ADP-ribosylation while GTP gamma S inhibits it. We show that GTP analogs permanently activate an ADP-ribosylating factor (ARF) which mediates CT action on retinal cell membranes: when transducin-depleted membranes were pre-activated by GTP analogs, re-added transducin became sensitive to CT in the absence of nucleotide, and presence of photoexcited rhodopsin (R*). Any subsequent G-nucleotide addition (even GDP) decreased ADP-ribosylation. Thus nucleotide-free transducin molecule in R*-Tempty complex is the CT substrate. PMID- 1936274 TI - A Saporin-6 cDNA containing a precursor sequence coding for a carboxyl-terminal extension. AB - Saporin-6 is a single-chain ribosome inactivating protein (RIP) from the seeds and the leaves of Saponaria officinalis (Caryophyllaceae). Here we have identified the COOH-terminal end of mature Saporin-6 and, by cDNA sequencing, the predicted carboxyl-terminal sequence of a leaf Saporin-6 primary translation product. Our data indicate that the characterized cDNA codes for a precursor containing a 22 amino acid carboxyl-terminal extension, not present in mature Saporin-6, that shows similarity to carboxyl-terminal propeptides of vacuolar proteins, suggesting that it may be involved in protein trafficking. PMID- 1936276 TI - Direct measurement of the equilibrium between glutathione and dithiothreitol by high performance liquid chromatography. AB - The equilibrium constant between reduced glutathione (GSH), oxidized glutathione (GSSG), reduced dithiothreitol (DTTSHSH), and oxidized dithiothreitol (DTTSS) has been directly measured by high performance liquid chromatography analysis of equilibrium mixtures. The equilibrium constant at 25 degrees C for the reaction GSSG + DTTSHSH in equilibrium 2GSH + DTTSS varies from approximately 200 M, below pH 8, to approximately 2800 M, above pH 11. The observed pH dependence is generally consistent with published values of acid dissociation constants of these thiols. PMID- 1936275 TI - Structure and organization of the gene encoding rat S-adenosylmethionine decarboxylase. AB - The gene for S-adenosylmethionine decarboxylase (AdoMetDC) was isolated from a rat genomic library using AdoMetDC cDNA as a probe. Nucleotide sequence analysis shows that the rat AdoMetDC gene consists of 8 exons which encode a protein identical to that inferred by a rat AdoMetDC cDNA sequence. The exons range in length from 43 to 1964 base pairs spanning 15672 bases of chromosomal DNA. All of the exon/intron junctions were found to conform to the consensus splice donor and acceptor sequences. Exon 8 corresponds to the 3' noncoding region of the 2 species of AdoMetDC mRNA which are formed by alternative utilization of 2 polyadenylation signals separated from each other by 1272 nucleotides. The transcription initiation site was located by S1 nuclease protection and by primer extension analysis, -325 nucleotides upstream of the translation initiation codon. The promoter region of the rat AdoMetDC gene contains a TATA box at -29 base pairs. No typical GC or CAAT boxes are located in the promoter, but six GC boxes and several putative binding sites for both tissue-specific and non specific transcription factors are found in the proximal part of intron 1. Southern blot analyses reveal a complex hybridization pattern suggesting that there are multiple copies of the AdoMetDC gene in the rat genome. PMID- 1936277 TI - Overexpression of alcohol oxidase in Pichia pastoris. AB - The protein import capacity of peroxisomes in methylotrophic yeasts was studied using Pichia pastoris containing one or two extra copies of the gene encoding the peroxisomal protein alcohol oxidase. The alcohol oxidase overproduced in this strain was only partially imported and assembled into the active, octameric form of the protein. The excess remained in the cytosol as protein aggregates composed of monomers. These results are discussed in view of the possible application of peroxisomes as storage compartments for heterologous proteins. PMID- 1936278 TI - Saccharomyces cerevisiae elongation factor 2 is phosphorylated by an endogenous kinase. AB - Mammalian cells contain a Ca2+/calmodulin-dependent protein kinase that specifically phosphorylates and inactivates elongation factor 2 (EF-2) in response to hormones and other agents which increase intracellular Ca2+ concentrations. Therefore, it has been proposed that the rate of translation in mammals is regulated by EF-2 phosphorylation. In the present study, EF-2 purified from the yeast Saccharomyces cerevisiae is shown to be a substrate for the mammalian EF-2 kinase. Furthermore, evidence was obtained using two-dimensional gel electrophoresis and peptide mapping which suggests that yeast EF-2 is a substrate for an endogenous kinase which phosphorylates the same site as the mammalian EF-2 kinase. Based on these findings, we propose that in yeast as in higher eukaryotes, the protein synthesis elongation cycle is regulated by phosphorylation of EF-2. PMID- 1936279 TI - Crystal structure of hevein at 2.8 A resolution. AB - The three-dimensional structure of hevein, a low molecular weight protein isolated from the latex of Hevea brasiliensis, has been determined by X-ray diffraction at 2.8 A resolution. The protein crystallizes in space group P2(1)2(1)2(1), with lattice constants a = 21.78, b = 31.86, c = 51.12 A. The structure was solved by molecular replacement methods using the domain C of wheat germ agglutinin (WGA) as search model. The positions and individual isotropic temperature factors of the 324 atoms have been refined by the Hendrickson and Konnert restrained refinement procedure. While tight restraints have been maintained on the bonded distances and angles, the R-factor has dropped to 24.1% and an averaged B value of 9.5 A2, using 78% (802) of the total possible number of reflections in the resolution range 5-2.8 A. The tertiary structure is very similar to that of domain C of WGA from residues 3-31. PMID- 1936280 TI - Measurements of cytoplasmic free Ca2+ concentration in human pancreatic islets and insulinoma cells. AB - In human pancreatic islets an increase in the glucose concentration from 3 to 20 mM raised the free cytoplasmic Ca2+ concentration [( Ca2+]i), an effect being reversible upon withdrawal of the sugar. Depolarization with a high concentration of K+ or the sulphonylurea tolbutamide also raised [Ca2+]i. Addition of extracellular ATP produced a transient rapid rise in [Ca2+]i. Oscillations in [Ca2+]i were observed in the presence of 10 mM glucose. Insulinoma cells responded to glucose and tolbutamide with increases in [Ca2+]i, whereas the sulphonamide diazoxide caused a decrease in [Ca2+]i. These findings confirm previous results obtained in rodent beta-cells. PMID- 1936281 TI - Functional properties of human thyroid hormone receptor beta 1 overexpressed using baculovirus. AB - We have overexpressed the human beta 1 thyroid hormone receptor in insect cells using a recombinant baculovirus to a level of 5-10% of total cellular protein. The recombinant protein migrates as a 50 kDa band by SDS-PAGE and Western blot analysis. The expressed receptor binds to L-T3 with a Kd of 1.3 +/- 0.4 x 10(-10) M and to thyroid hormone analogues with an affinity hierarchy of TRIAC greater than L-T3 greater than L-T4 greater than rT3. Gel retardation assays show highly specific receptor binding to a TRE which is modified by the presence of ligand and avidin-biotin complex DNA analysis shows a Kd of 6.2 +/- 2.0 x 10(-10) M for this interaction. These results indicate high level expression of hTR beta with authentic hormone and DNA binding properties. PMID- 1936282 TI - Identification and partial purification of GTPase-activating proteins from yeast and mammalian cells that preferentially act on Ypt1/Rab1 proteins. AB - Two GTPase-activating proteins of apparent molecular mass of 100 kDa and 30 kDa have been partially purified from porcine liver cytosol using mammalian Ypt1/Rab1 protein as substrate. Both proteins act most efficiently on Ypt1/Rab1p, but are inactive with H-Ras p21. From the budding yeast Saccharomyces cerevisiae, a cytosolic 40 kDa yptGAP was partially purified. It accelerates the intrinsic GTPase activity of wild-type Ypt1p but not of H-Ras p21 or a mutant ypt1p with an amino acid substitution of the effector domain which renders the protein functionally inactive in yeast cells. PMID- 1936283 TI - Purification and spectral characterization of a b-type cytochrome from the plasma membrane of the archaebacterium Sulfolobus acidocaldarius. AB - For the first time the purification of a heme-b containing cytochrome from the plasma membrane of an extremely thermoacidophilic archaebacterium is described. The detergent solubilized 30 kDa polypeptide contains two heme-b centers and one copper ion. According to its low temperature spectra and CO-binding properties, it is likely to function as a cytochrome-o like terminal oxidase in the membrane. The purified cytochrome does not retain catalytic activity, however. PMID- 1936284 TI - Interaction of mastoparan with the low molecular mass GTP-binding proteins rho/rac. AB - Mastoparan, which has been shown to active G proteins, inhibits the ADP ribosylation of 20 kDa human platelet membrane proteins catalyzed by Clostridium botulinum exoenzyme C3 half-maximally and maximally (90%) at 20 and 100 microM concentrations, respectively. Inhibition of ADP-ribosylation was enhanced by GTP gamma S. Mastoparan increased GTP hydrolysis by porcine brain rho protein and stimulated GTP binding in a concentration dependent manner. The data suggest that mastoparan not only interacts with heterotrimeric G proteins but also with low molecular mass GTP-binding proteins of the rho/rac family. PMID- 1936285 TI - Lipid-peptide interactions between fragments of the transit peptide of ribulose 1,5-bisphosphate carboxylase/oxygenase and chloroplast membrane lipids. AB - The interactions of fragments of the transit peptide of ribulose-1,5-bisphosphate carboxylase/oxygenase with lipid monolayers was studied in order to investigate the possible involvement of the membrane lipids in the protein import process. The fragments are surface active and have a differential ability to insert in lipid monolayers. The fragments have a preference for the chloroplast galacto- and sulpholipids and phosphatidylglycerol and interact with envelope membrane lipid extracts. These results suggest that probably transit peptide-lipid interactions are involved in the chloroplast protein import process. PMID- 1936286 TI - A method to study the rapid phosphorylation-related modulation of neutral trehalase activity by temperature shifts in yeast. AB - Heat shock enhanced the synthesis of neutral trehalase in growing cells of Saccharomyces cerevisiae, as detected by immunological methods. The activity of the enzyme was measured in extracts obtained by two methods: cells were either harvested by filtration and subsequent disruption with glass beads at 0-4 degrees C or immediately frozen with liquid nitrogen in the presence of Triton X-100, followed by thawing at 30 degrees C. The first procedure yielded artificially high activities of neutral trehalase in heat-shocked cells due to rapid (less than 1 min) activation during handling at 4 degrees C before homogenization. Activity of the enzyme in these homogenates decreased 75-90% upon a treatment with alkaline phosphatase, indicating that activation was due to phosphorylation. The second procedure yielded low trehalase activities for heat-shock treated cells, much higher activities for cells shifted back for some seconds to 27 degrees C, and very low activities again for cells shifted from 27 to 40 degrees C for a second time. Thus, permeabilization of cells following rapid freezing in Triton X-100 is a method of choice to study post-translational modulation of the neutral trehalase of S. cerevisiae by phosphorylation and dephosphorylation. PMID- 1936287 TI - Heat shock increases turnover of 90 kDa heat shock protein phosphate groups in HeLa cells. AB - The 90 kDa heat shock protein (hsp90) is a major phosphoprotein which associates various other cellular polypeptides such as actin, calmodulin, steroid hormone receptors and certain protein-kinases. Little is known about the function of hsp90 in recovery from stress. In this report, we describe a dramatic increase in the rate of both phosphate uptake and dephosphorylation of hsp90 in HeLa cells submitted to acute stresses. This increased turnover of hsp90 phosphate groups might reflect a greater protein binding activity of hsp90 in stressed cells. PMID- 1936288 TI - Identification of the metal coordinating residues in the DNA binding domain of the glucocorticoid receptor by 113Cd-1H heteronuclear NMR spectroscopy. AB - Two-dimensional 1H-113Cd HSQC and relay HSQC experiments were performed on the 113Cd substituted DNA binding domain of the rat glucocorticoid receptor. The results of these experiments combined with sequence-specific assignments allowed the identification of all coordinating cysteines. It was found that C495 and not C500 is the fourth coordinating cysteine in the second zinc-finger. A signal at approximately 2 ppm previously assigned to a epsilon-CH3 of a methionine residue coordinating to a third, weakly bound, cadmium ion, was identified as the C443 beta proton ligating to the metal ion in the first zinc-finger. No indications were found for the presence of a previously suggested third metal ion binding site. PMID- 1936289 TI - Randomized clinical trials in surgical oncology. AB - Are randomized clinical trials needed to evaluate new therapies? Judging from the number of randomized trials which get published in medical journals, the answer seems to be unequivocally positive. No new drug may be put on the market without at least two randomized studies showing its benefit. In comparison, prospective, controlled and randomized studies are rather more sparse in the evaluation of new surgical approaches. Moreover, the kinds of trials that are performed to test new anti-cancer drugs may not provide an appropriate model to establish the worth of treatments given as adjuvant to surgery. This paper briefly discusses some reasons why trials should be more common in surgical oncology, and some ways in which they could be made more pertinent. PMID- 1936290 TI - Multiple primary malignant neoplasms. AB - The occurrence of multiple malignant tumours has been recorded, usually as individual cases but also in groups from tumour registries or autopsy studies. A personal series of 71 cases encountered in the follow-up clinics of two District General Hospitals is presented. Cases of multiple skin tumours, and of intestinal growths associated with pernicious anaemia, ulcerative colitis and familial polyposis have been excluded. Review of the literature has been carried out and possible aetiological factors have been considered. The importance of the functions of the tumour surveillance mechanism is emphasized, and the possibility of depression of the defence mechanism by major surgery, is considered to be of importance. Assessment of the patient's defence mechanisms may be as important as grading and staging the tumours. PMID- 1936291 TI - Surgical treatment of dermatofibrosarcoma protuberans. A retrospective study of 20 cases with review of literature. AB - The clinicopathological features and results of surgical treatment of 20 patients with dermatofibrosarcoma protuberans (DFSP) were reviewed. All patients have been observed until the present time or death. The primary treatment usually consisted of marginal, wide or radical excision. Re-excision because of recurrence was performed in six of the 20 patients who were treated primarily only by marginal excision. Following re-excision two patients have remained disease-free until the present, the other four of these six patients had a second recurrence. Three of these four patients with a second relapse were successfully treated by excision. Although six patients out of 20 had 13 recurrences at the site of primary therapy, no patient developed lymph node or distant metastases. To date, none of the remaining 14 patients has had recurrence, all having been treated by excision of from 1 to 5 cm, the mean follow-up time was 8.75 years. Based on our data, the high recurrence rate after marginal surgical treatment implies an initial radical resection. PMID- 1936292 TI - Theoretical considerations in relation to the treatment of brain tumours by means of local hyperthermia generated by ultrasound fields. AB - Brain tumours comprise a significant fraction of all tumours in the human body. Despite the development of technology in clinical oncology, these tumours still present a difficult challenge. The margin between destruction of tumour and damage to normal tissue is narrow in the brain. The price paid for producing tissue damage outside the tumour is high in terms of quality of survival. Results of many experiments with ultrasound hyperthermia show that this new technique is successful for treating certain types of malignant tumours. In the case of brain tumours, applying focused fields should have the advantage of selectively destroying the tumour and leaving surrounding tissues intact. Previous attempts at applying ultrasound to the field of neurosurgery are reviewed. Those factors which have effects on the generation of thermal fields in brain tissues are considered in relation to the possible treatment of human brain tumours. Calculated thermal fields in a 2-D brain model generated by an applicator built in our laboratory are also presented. PMID- 1936293 TI - Locating and marking non-palpable, mammographically suspicious breast lesions with the aid of ultrasound. AB - Most non-palpable, mammographically suspicious breast lesions can be located by ultrasound (47 of 58 lesions in our series). We found that it was possible in 26 of 28 cases to mark these lesions prior to operation under ultrasound guidance thus simplifying the operating procedure. PMID- 1936294 TI - Preoperative localization and surgical approach in 344 cases of non-palpable breast lesions. AB - From June 1985 to August 1989, 344 cases of mammographic non-palpable breast lesions were operated on at the National Cancer Institute in Milan. The mammographic findings consisted of clusters of microcalcifications in 162 cases (42.1%), suspicious opacities with irregular borders in 116 cases (37.7%) and opacities containing microcalcifications in 66 cases (19.2%). The mean age of the patients was 51 years (range 31-77 years). In all patients localization was performed 1 day before the operation, introducing a self-retaining anchor wire into the mammary parenchyma. The histological findings showed benign breast disease in 184 cases (53.4%); proliferative dysplasia without atypia in 150 cases (81.5%); proliferative dysplasia with atypia in 22 cases (12%); fibroadenoma in nine and papilloma in three cases. Of 160 patients with carcinoma, 37 had non infiltrating carcinoma: 28 of these cases (17.5%) had non-infiltrating ductal carcinoma and nine cases (5.6%) had lobular carcinoma in situ. In the 123 cases with infiltrating breast cancer the histological types were ductal infiltrating carcinoma (32.5%), lobular infiltrating carcinoma (9.8%), and 34.1% of the cases an associated or prevalent intraductal carcinoma was found. In 138 cases (85.6%) a conservative surgical procedure (quadrantectomy or more limited excision) was done, and in 22 (14.4%) cases a total mastectomy was necessary because of the extent of the disease. Axillary dissection was performed in 116 of the 123 patients with histological invasive carcinoma. Nodal metastases were found in 24 cases (20.7%), and only one node was involved in nine of the cases (37.5%), two to three nodes in nine cases (37.5%) and four to ten nodes in six cases (25%). PMID- 1936295 TI - Histopathological study of vesical carcinoma in Plateau State, Nigeria. AB - Thirty-eight cases of vesical carcinoma, diagnosed at the Jos University Teaching Hospital during a 6-year period, were reviewed. Malignant tumours of the urinary bladder represent 2.7% of all cancers and the prevalence rate of vesical carcinomas is 6.7 per 100,000. Squamous cell carcinoma accounts for 52.6% of all cases whilst transitional cell, mixed and adenocarcinomas constitute 26.3%, 15.8% and 5.3%, respectively. Generally, the male: female ratio is 2.5: 1 and most tumours occur in the fifth decade of life. Schistosomiasis endemicity is believed to be responsible for the preponderance of the squamous cell carcinoma type. PMID- 1936296 TI - Complications of radical hysterectomy in women with early stage cervical cancer: clinical analysis of 270 cases. AB - During a 25 year period, 270 cases of stage IB and IIA cervical cancer were subjected to radical hysterectomy and lymphadenectomy. The morbidity rate was 27.6% and mortality rate was 0.3%. While injuries to the great vessels were the most common intra-operative complications, the most frequent postoperative complications were in the urinary system. The leading causes of morbidity were bladder dysfunction (16.2%), urinary infection (5.9%), lymphocyst (6.4%) and wound infections (3.5%). While the overall complications seem high, the frequency of serious morbidity has diminished and radical hysterectomy now represents one of the accepted methods of treatment of cervical carcinoma, with good 5-year survival rates. PMID- 1936297 TI - Immunoscintigraphy of colorectal cancer using a monoclonal antibody 77-1. AB - The monoclonal antibody (mAb) 77-1 recognizes epithelial membrane antigen (EMA) expressed by the majority of colorectal cancers. Following administration of indium-111 labelled 77-1, gamma camera imaging was carried out on 16 patients with known or suspected colorectal cancer prior to surgery or endoscopic laser therapy. Fourteen of the patients were found to have cancer, with one patient having two primary lesions. Two patients suspected of tumour recurrence were not found to have a lesion at laparotomy. Imaging before operation or laser therapy detected 10 out of 15 lesions (67%). Tumours which produced positive images were found to express the target antigen on immunocytochemical staining of the excised tumours. A mean tumour to normal colon ratio of 1.63 +/- S.D. 0.46 and a mean tumour to blood ratio of 3.60 +/- 1.48 were found at day 6 after antibody administration. A high uptake of radiolabel by the liver prevented the detection of hepatic metastases, present in three patients. Of the two patients with suspected recurrence a false positive scan was found in one owing to the presence of inflammatory tissue. Indium-111 labelled 77-1 may have a role in the imaging or targeting of colorectal cancer. PMID- 1936298 TI - The extended Hartmann operation as an elective procedure for rectal cancer. A forgotten operation. AB - The authors describe their experience with the extended Hartmann procedure as the elective and definitive operation in a selected group of 36 patients having primary adenocarcinoma of the rectum. The operations were carried out between 1st January 1978 and 31st December 1989. The average age of the patients was 70 years (range 37 to 84 years). Ten patients had preoperative radiotherapy because of deep infiltration and (or) fixation of the tumor. In this series the Hartmann procedure was chosen because abdomino-perineal excision was not needed and low anterior resection could not warrant acceptable continence. With a Hartmann procedure the risks of a low colorectal or colo-anal anastomosis were avoided while the perineal excision was abandoned. Eight patients had hepatic metastases. The Dukes' classification of the remaining patients was A in two, B in nine and C in 17 patients. Postoperative morbidity was within acceptable limits for this particular patient group. There was no hospital mortality. Twenty patients had a potentially curative resection prior to 31st December 1987, thus making them available for follow-up of at least 2 years. Ten of these patients have been in follow-up without evidence of disease for an average of 76 months (mean 65 months, range 28-123 months). The authors conclude that the procedure is safe and that the remaining rectal stump does not generate morbidity or discomfort. Considering the fact that only two of the 36 patients had a Dukes' A tumor, the low recurrence rate shows that the Hartmann procedure yields satisfactory pelvic radicality. PMID- 1936299 TI - The value of colonoscopic surveillance following a diagnosis of colorectal cancer or adenomatous polyp. AB - Conventional follow-up of patients with colonic neoplasia will at best only identify symptomatic lesions and those visible with a sigmoidoscope, and will therefore fail to identify new malignant lesions in time for effective treatment. In 1980 we began a prospective study of the efficacy and feasibility of replacing conventional outpatient follow-up with annual colonoscopic surveillance. One hundred and fifty-eight patients, attending one surgeon, have been entered: 74 patients who had a curative resection for colorectal carcinoma and 84 patients who had endoscopic or local resection of an adenoma. In the carcinoma group (mean follow-up 4.3 years, range 1-21), 40 of 237 colonoscopies were positive (17%) in 27 patients (36%). Forty-eight polyps were removed endoscopically and two asymptomatic recurrent carcinomas identified. In the adenomatous polyp group (mean follow-up 4 years, range 1-11), 40 of 252 colonoscopies were positive (16%) in 29 patients (34%). Fifty polyps were removed endoscopically, including two which had become malignant. All patients were also screened by Haemoccult stool testing, in the hope that it would identify these lesions and allow the frequency of colonoscopy to be reduced. Unfortunately, Haemoccult testing failed to identify many lesions, including one carcinoma and one malignant polyp. Our experience suggests that colonoscopic follow-up of all patients with colonic neoplasia attending one surgeon is a feasible exercise which can and should replace outpatient appointments for clinical examination. PMID- 1936300 TI - Adjuvant hepatic intra-arterial chemotherapy after potentially curative hepatectomy for liver metastases from colorectal cancer: a pilot study. AB - The site most at risk of recurrence after hepatectomy is the remaining liver. Therefore a study was conducted of the use of hepatic intra-arterial and oral chemotherapy for colorectal metastases to prevent intrahepatic recurrence. Our regimen consisted of intra-arterial 5-fluorouracil (5-FU), mitomycin C (MMC) and oral 1-hexylcarbamoyl-5-fluorouracil (HCFU). Sixteen patients were treated. Median total dose of 5-FU was 8.1 g, MMC was 43 mg, and HCFU was 54 g, respectively. Median follow-up period was 21 months. The recurrence rate of the remaining liver was 31%. With respect to the number of hepatic metastases, there was no recurrence in patients with a single deposit. On the other hand, the intrahepatic recurrence rate of patients with multiple deposits was 45%. Of six patients with more than five hepatic deposits, however, only one patient had developed recurrent disease in the liver. Chemical sclerosing cholangitis (19%) was the most serious complication. Consequently, we propose that a prospective randomized trial should be carried out to establish the effects of this type of adjuvant chemotherapy to reduce possible recurrences in the remaining liver. PMID- 1936301 TI - Hepatic recurrence not prevented with low-dosage long-term intraportal 5-FU infusion after resection of colorectal liver metastasis. AB - Seventeen patients with colorectal cancer metastatic to the liver underwent hepatic resection. For five we prescribed adjuvant therapy which included intraportal mitomycin C (MMC) and 5-fluorouracil (5-FU) and consecutive oral administrations of tegafur (N1-(2'-tetrahydrofuryl)-5-fluorouracil), in an attempt to reduce recurrences in the liver. Intraportal chemotherapy consisted of low-dosage, long-term 5-FU infusion, 40 days at 250 mg/day, and a 10 mg bolus injection of MMC at the start and the end of continuous 5-FU infusion. With regard to postoperative events in patients given the infusion therapy, there was no hepatotoxicity or hematologic toxicity, no mechanical complications and no pain or vomiting. Two of five patients given infusion therapy and six of 12 not given the therapy died within 5 years after surgery. There was recurrence in the liver in two patients given infusion therapy and in four not given the therapy. Although low-dosage, long-term intraportal chemotherapy is a safe treatment given hopefully to prevent hepatic recurrence, we found no beneficial effect. PMID- 1936302 TI - Value of follow-up in the management of recurrent colorectal cancer. AB - The purpose of this article was to study the effectiveness of a prospective follow-up programme in patients after curative surgery for colorectal cancer. Of the initial 151 selected patients, 61 (40%) developed a recurrence in whom only six cases (10%) of potentially curable recurrent lesions were detected. The first clues to recurrence in the 61 patients were history or physical examination in 49%, a rising CEA in 29% and a positive imaging finding in 10%, being difficult to decide which test first signalled a recurrent cancer in an additional 11%. Endoscopy and CEA determinations were the most rewarding investigations. CEA was a sensitive means of identifying disseminated recurrent disease and liver metastases compared with liver function tests or liver ultrasound every 3 months. Endoscopy was useful in the diagnosis of local recurrences. However no follow-up test was capable of detecting recurrent colorectal cancer when it might still have been curable. As a direct result of this follow-up programme 15 patients (23%) underwent re-exploration. No symptomatic patients were candidates for curative re-operation. Of the asymptomatic patients six (four colonic and two rectal cancers) (19.5%) were re-resected for cure. Only three of these were alive and without evidence of disease, 40, 43 and 69 months later so that long term survivors after curative re-resection represent only 5% of all patients with recurrences (7.2% of the recurrent colonic cancer and 3% of the rectal cancer). Our follow-up programme did not permit us to alter the incidence of disseminated recurrent disease, and the effectiveness of the curative re-resection represents an increase of only 1.3% in the global 5-year survival rates for colorectal cancer. Our study does not demonstrate any great value of 'classical' postoperative follow-up programme. PMID- 1936303 TI - Optic nerve involvement in nasopharyngeal carcinoma. AB - Five rare cases of nasopharyngeal carcinoma with optic nerve involvement are reported. Computerised Tomographic Scan (CT Scan) studies were performed in four of them. Evidence of intracranial spread of the tumour, from the roof of the fossa of Rosenmuller to the apex of the orbit through the cavernous sinus, was noted in three patients. In one of them there was extracranial extension of the tumour, to the orbit through the posterior ethmoid. PMID- 1936304 TI - Treatment of metastatic para-aortic paraganglioma by surgery, radiotherapy and I 131 mIBG. AB - A patient with a malignant, functioning, aortico-sympathetic paraganglioma and a solitary bone metastasis causing paraplegia was treated by spinal decompression, irradiation of the metastasis, surgical excision of the primary tumour and systemic I-131 meta-iodobenzyl-guanidine (mIBG). Sixteen months after treatment there was no clinical, radiological or biochemical evidence of residual disease and neurological function was restored. The case supports the use of combined treatment incorporating mIBG in patients with metastatic neuroendocrine tumours which demonstrate mIBG uptake. PMID- 1936305 TI - Derangement of adipose tissue: a case report of multicentric retroperitoneal liposarcomas, retroperitoneal lipomatosis and multiple subcutaneous lipomas. AB - No aetiological factors are at present known in the pathogenesis of liposarcomas. Benign lipomatous disorders, such as lipomas and lipomatosis, generally do not predispose to the development of liposarcomas. A case is presented of a patient with multicentric retroperitoneal liposarcomas, associated with retroperitoneal lipomatosis and preceded by a long history of multiple subcutaneous lipomas. In the literature this combination has not been described. This rare combination of lipomatous disorders seems to indicate a common derangement of adipose tissue. PMID- 1936306 TI - Fatal haemoperitoneum as a result of liver metastases from nasopharyngeal cancer. AB - Spontaneous rupture of hepatic metastases is rare, there being only 22 cases documented in the literature. We report here the first such case owing to nasopharyngeal carcinomatous metastases. This is of interest because in South East Asia ruptured hepatocellular carcinoma is the usual cause of fatal haemoperitoneum. PMID- 1936307 TI - Primary B-cell immunoblastic lymphoma of pancreas. AB - Extranodal lymphoma may present as an abdominal mass without evidence of disease elsewhere. Predominant pancreatic involvement with lymphoma is rare. Presenting as a pancreatic mass, it may be difficult to differentiate if from carcinoma. Ultrasound-guided fine needle biopsy and immunocytochemistry are helpful in establishing a histological diagnosis. It is important to differentiate lymphoma from carcinoma, because lymphoma is treated differently and has a better prognosis. PMID- 1936308 TI - A simpler technique for reduction of uterine septum. AB - Hysteroscopic resection of the uterine septum is currently the accepted technique for dealing with this congenital uterine abnormality. Its advantages over the transabdominal approach are: it can be performed on an outpatient basis, it requires minimal recovery time, and it does not commit the patient to a subsequent cesarean section. This communication reports on a new transcervical approach that does not require the use of a hysteroscope. Thirty-four patients have now undergone resection of uterine septae using this technique. The results have been consistently good, requiring a short operative time and minimal instrumentation. We have experienced no complications. PMID- 1936309 TI - Treatment of persistent ectopic pregnancy--complications? PMID- 1936310 TI - Value of ultrasound-guided embryo transfer. PMID- 1936311 TI - Oral contraceptives and breast disease. AB - Epidemiologic data support the hypothesis that the types of OCs used before the mid-1970s protected against most forms of benign breast disease. It is unclear whether current low-dose progestogen OCs will confer the same protection. Further studies are necessary to clarify this. For breast cancer, the relationship is more complex. It is possible that prolonged use of high-dose OCs exert a small increased risk for breast cancer development in women before age 45. Furthermore, prolonged use before a first term pregnancy may result in a small increase in risk for breast cancer before age 45. Studies evaluating the effect of current low-dose OCs are necessary to elucidate what, if any, effect they may have on breast cancer development. Furthermore, as our population ages, studies will be able to determine what effect, if any, may be present in women over age 60, those women with the highest underlying risk of breast cancer. And finally, more research of basic breast tissue physiology and the effect of endogenous and exogenous hormones on this complex organ is needed. PMID- 1936312 TI - Hormonal therapy of endometriosis: the estradiol target. PMID- 1936313 TI - Utility and predictive value of a rapid measurement of urinary pregnanediol glucuronide by enzyme immunoassay in an infertility practice. AB - STUDY OBJECTIVE: To assess the clinical utility of measuring urinary pregnanediol glucuronide in random samples in an infertility practice. DESIGN: Samples of urine were collected from patients approximately 3 weeks from their last menstrual period to ascertain if ovulation had occurred. Each sample was tested for specific gravity before analyzing for pregnanediol glucuronide. Simultaneous venipuncture was performed to compare results from the urinary assay to quantitative measures of serum progesterone (P). SETTING: All patients were randomly sampled. PATIENTS: Three hundred ninety women undergoing pituitary down regulation with leuprolide acetate were chosen for study because they routinely initiate medication after documentation of ovulation. OUTCOME MEASURES: The performance of the urinary pregnanediol glucuronide was evaluated as to its sensitivity, specificity, predictive value, and test efficiency compared with a serum measurement of 2.5 ng/mL and 10.0 ng/mL. RESULTS: The performance characteristics of the pregnanediol glucuronide assay were directly related to the hydration status of the patient at the time of sample collection. Regardless of urine specific gravity, if pregnanediol glucuronide was qualitatively detected (greater than 3 micrograms/mL), serum P was greater than 2.5 ng/mL. However, in cases in which pregnanediol glucuronide was undetected (less than 3 micrograms/mL), results were only accurate when the specific gravity was greater than or equal to 1.020. When comparing urinary pregnanediol glucuronide values to serum greater than 10 ng/mL, both specificity and predictive value of a positive test decreased because of increased numbers of false-positive results. CONCLUSIONS: The enzyme immunoassay measurement for pregnanediol glucuronide may replace the use of serum P in documenting the ovulatory status of many patients. However, all specimens must be checked for specific gravity and if less than 1.020, a serum P should be used to ensure accuracy. PMID- 1936314 TI - Histology of proximal tubal obstruction in cases of unsuccessful tubal canalization. AB - OBJECTIVE: To determine possible etiologies of unsuccessful fluoroscopically guided tubal canalization, we studied the histology of tubal segments in cases of failed canalization for proximal tubal obstruction. Factors contributing to cases of unsuccessful fluoroscopically guided tubal canalization remain unclear. DESIGN: Prospective. SETTING: Reproductive Endocrinology Clinic. MATERIALS: Twenty-seven cornual and/or isthmic tubal segments from 15 patients who underwent proximal tubal surgery after fluoroscopically guided tubal canalization were studied. Specimens were prepared with hemotoxylin-eosin and Masson trichrome stains. RESULTS: Histologic examination of excised cornual and isthmic tubal segments revealed abnormalities in 93% of specimens. Obliterative fibrosis (61%), chronic salpingitis (57%), and salpingitis isthmica nodosa (42%) were the most commonly found histologic tubal abnormalities. One case of complete tubal occlusion and tubal schistosomiasis was also detected. CONCLUSIONS: These data suggest that cases of failed fluoroscopically guided tubal canalization may be secondary to severe intrinsic tubal disease and tubal occlusion and not to the technique. Fluoroscopically guided tubal canalization may provide a means of differentiating a functional obstruction amenable to conservative management from true occlusion requiring management by microsurgical techniques or in vitro fertilization. PMID- 1936315 TI - Is it possible to run a successful ovulation induction program based solely on ultrasound monitoring? The importance of endometrial measurements. AB - OBJECTIVE: To attempt the monitoring of ovulation induction solely with ultrasound (US). DESIGN: Using serial US measurements to monitor ovulation induction using human menopausal gonadotropin and human chorionic gonadotropin (hCG), in comparison with estradiol (E2) concentrations that became available at the end of each cycle. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Twenty hypogonadotropic and 29 ultrasonically diagnosed polycystic ovary patients. MAIN OUTCOME MEASURE: Follicular growth, uterine measurements, endometrial thickness, and serum E2 concentrations. RESULTS: Follicular growth, uterine measurements, and endometrial thickness correlated strongly with E2 concentrations (P less than 0.0001). The endometrium on the day of hCG administration was significantly thicker (P less than 0.01) in the conception (n = 27) compared with the nonconception cycles (n = 87), whereas no significant difference were observed in serum E2 concentrations. No pregnancy was observed when hCG had been administered when the endometrial thickness was less than or equal to 7 mm. Midluteal endometrial thickness of greater than or equal to 11 mm was found to be a good prognostic factor for detecting early pregnancy (P less than 0.008). CONCLUSIONS: Serial US examinations used alone have proven to be safe and highly efficient. It also has a unique ability to detect pregnancy in the midluteal phase. PMID- 1936316 TI - Comparative morphometric study of the endometrium, the fallopian tube, and the corpus luteum during the postovulatory phase in normally menstruating women. AB - OBJECTIVE: To compare function and histologic structure of the corpus luteum (CL) to the morphology of the endometrium and the fallopian tube in normally menstruating women. DESIGN: Circulating steroid and luteinizing hormone (LH) levels were compared with CL steroid production in vitro and the histology of CL, endometrium, and the fallopian tube at four stages of the postovulatory phase (days LH +/- 0/LH+3, LH+4/LH+7, LH+8/LH+11, LH+12/onset of menstruation). SETTING OF PATIENTS: The study included 28 volunteers with proven fertility undergoing surgical sterilization timed in relation to the LH surge. INTERVENTIONS: Blood and urine samples for LH, progesterone (P), and estradiol assessment were obtained before (simultaneously with ultrasound examinations), during, and after operation. Biopsy specimens from CL, endometrium, and fallopian tube were taken at the surgical sterilization and subjected to morphometric analyses. MAIN OUTCOME MEASURES AND RESULTS: Significant correlation was found between the endometrial dating and the LH surge (r = 0.923) and between the dating of the endometrial and CL biopsies (r = 0.918). A significant correlation (P less than 0.01) existed between circulating P levels and two endometrial indices; the number of vacuolated cells (LH+4/LH+7) and the glandular diameter (LH+8/LH+11). CONCLUSION: In normally menstruating women, the endometrial biopsy is likely to closely gauge the CL activity provided the biopsy is timed in relation to the LH surge. PMID- 1936317 TI - Controlled preparation of the endometrium with exogenous estradiol and progesterone in women having functioning ovaries. AB - OBJECTIVE: To determine if controlled preparation of the endometrium with exogenous estradiol (E2) and progesterone (P) could be achieved in women retaining their ovarian function without requiring prior ovarian suppression with a long-acting agonist of gonadotropin-releasing hormone (GnRH-a). DESIGN: Prospective feasibility study of a new simplified hormone regimen for preparation of endometrium receptivity. Six volunteer women received transdermal E2 and vaginal P without prior suppression of their ovarian function with GnRH-a. The control group consisted of previously reported cases receiving GnRH-a and E2 and P. SETTING: Academic tertiary care institution. PATIENTS: Six volunteer women. MAIN OUTCOME MEASURES: Participants received transdermal E2 and P after a regimen designed to duplicate the plasma E2 and P levels seen in the menstrual cycle. INTERVENTION: Endometrial biopsy. RESULTS: Plasma luteinizing hormone increased to surge levels in one woman on day 11, in two on day 12, and on day 14 in the remaining three women. No follicular growth was noticed on ultrasound, and no increase in plasma P occurred before the onset of P administration on day 15. Day 20 endometrium specimens showed early secretory changes as previously reported in women deprived of ovarian function receiving similar hormonal treatment. CONCLUSIONS: Our results indicate that controlled preparation of the endometrium can be achieved with exogenous E2 and P without prior ovarian suppression with a GnRH-a in women having functioning ovaries. Hence, administration of exogenous E2 and P appears to be a viable simpler alternative to the combined administration of GnRH-a and exogenous E2 and P, which avoids the side effects and the cost of GnRH-a. PMID- 1936318 TI - Three types of polycystic ovarian syndrome in relation to androgenic function. AB - OBJECTIVE: To re-evaluate the concept of polycystic ovarian syndrome (PCOS) in view of androgenic function. DESIGN: Patients were studied endocrinologically and ultrasonographically. SETTING: This study was performed as a clinical investigation. PATIENTS, PARTICIPANTS: Sixty-nine euprolactinemic anovulatory patients with luteinizing hormone (LH) hypersecretion and 18 normal volunteers were selected. INTERVENTIONS: One hundred micrograms of LH-releasing hormone were administered. MAIN OUTCOME MEASURE(S): It was possible to divide PCOS patients into three types. RESULTS: Patients with neither hirsutism nor elevation of serum androstenedione (delta 4) and/or testosterone (T) were designated as type I PCOS (n = 20). Patients without hirsutism but with elevated delta 4 and/or T were referred to as type II PCOS (n = 33). Patients with both hirsutism and elevation of delta 4 and/or T were defined as type III PCOS (n = 16). Concentrations of delta 4 appeared gradedly increasing in types I, II, and III in that order, whereas T concentrations were significantly higher in types II and III than in control. Ultrasonographically, cystic ovaries were found in 88%, 84%, and 100% of types I, II, and III patients, respectively. CONCLUSIONS: It is postulated that each type may represent a subset of whole spectrum of PCOS from Stein-Leventhal syndrome to simple anovulation with LH hypersecretion. PMID- 1936319 TI - High CA-125 concentrations in peritoneal fluid of normal cyclic women with various infertility-related factors as demonstrated with two-step immunoradiometric assay. AB - OBJECTIVE: To determine CA-125 concentrations and total amounts in peritoneal fluid (PF) of women with various infertility-related factors throughout the menstrual cycle. DESIGN: Peritoneal fluid was obtained at laparoscopy. CA-125 was determined using the assessed two-step immunoradiometric assay (IRMA) which, in contrast to the one-step IRMA, gives valid results. SETTING: University Hospital Nijmegen, Nijmegen, The Netherlands. PATIENTS: One hundred six infertile women with a regular and ovulatory cycle were included. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): The mean PF CA-125 concentration and total amount were significantly lower during the luteal phase as compared with other phases of the menstrual cycle. No correlation was found with the presence or absence of endometriosis, adhesions, a male and/or cervical mucus infertility factor, and with patent or closed fallopian tubes. RESULTS: Peritoneal fluid CA-125 concentrations varied from 630 to 12,000 arbitrary units/mL (mean +/- SD = 3,437 +/- 2,286). Total PF CA-125 amounts (concentration x PF volume) varied from 1,760 to 13,300 arbitrary units (mean +/- SD = 30,219 +/- 26,841). CONCLUSIONS: CA-125 secretion into the abdominal cavity varies during the menstrual cycle. Retrograde menstruation is not the main source of CA-125 in PF. PMID- 1936320 TI - Transvaginal color flow Doppler in the assessment of ovarian and uterine blood flow in infertile women. AB - OBJECTIVE: To measure the flow velocity of the uterine and ovarian arteries through the menstrual cycle to determine there are changes. DESIGN: Serial measurements throughout the menstrual cycle in women attending an infertility clinic, compared with volunteers coming for annual examinations. Transvaginal ultrasound-color flow Doppler was the investigative tool. SETTING: A University Hospital ambulatory care center. PATIENTS: One hundred infertile women compared with 150 women attending the clinic for annual checkups. MAIN OUTCOME MEASURES: Changes in the resistance index of flow velocity waveforms of the uterine and ovarian arteries. RESULTS: Uterine flow velocity has a resistance index of 0.88 +/- 0.04 (2 SE) in the proliferative phase and starts to decrease the day before ovulation. A nadir of 0.84 +/- 0.04 is reached on day 18 and remains at that level for the rest of the cycle. In anovulatory cycles, these changes do not occur. A subgroup of 12 women who lacked end diastolic flow in the uterine arteries during the secretory phase were identified. Eleven of these women were infertile, 8 of whom with primary infertility. Ovarian artery flow velocity is usually detected when the dominant follicle reaches 12 to 15 mm. The resistance index is 0.54 +/- 0.04 and also declines on the day before ovulation. A nadir of 0.44 +/- 0.04 is reached 4 to 5 days later and slowly rises to 0.050 +/- 0.04 before menstruation. CONCLUSIONS: There are changes in the flow velocity patterns of the uterine and ovarian arteries during the normal ovulatory menstrual cycle. Because these changes in flow velocity begin before ovulation, it can be suspected that they may involve angiogenesis as well as hormonal factors. The changes noted in these studies are statistically significant but may be too small to be used as a diagnostic tool in the study of infertility problems. PMID- 1936321 TI - Chromosome studies in human unfertilized oocytes and uncleaved zygotes after treatment with gonadotropin-releasing hormone analogs. AB - OBJECTIVE: To determine the frequency of the anomalies from the cytogenetic point of view in the oocytes remaining from our in vitro fertilization (IVF) program. Two gonadotropin-releasing hormone analogs (GnRH-a) were used (buserelin acetate and leuprolide acetate) in the superovulation treatment. DESIGN: A prospective study was planned in January 1989. Deadline for data and quantitative analysis was to be July 1990. SETTING: Hospital de Cruces, a public and tertiary institute. PATIENTS: One hundred thirty-nine IVF patients, yielding 433 oocytes. Selected on the basis of availability of oocytes and staff. RESULTS: Two hundred thirty-eight oocytes (71.25%) exhibited the normal number of metaphase II chromosomes; 64 (19.16%) exhibited aneuploidy; 13 (3.89%) were diploid, hyperdiploid, or hypodiploid; and 19 (5.68%) showed parthenogenetic activation. Of the 99 zygotes, 17 were polyploid and 48 showed prematurely condensed chromosomes, whereas in 31 cases the male and female pronuclei remained separate. CONCLUSIONS: It would not appear that the rate of chromosomal anomalies is affected after pituitary suppression with GnRH-a. PMID- 1936322 TI - Human ovarian granulosa cell culture: determination of blood cell contamination and evaluation of possible culture purification steps. AB - OBJECTIVE: To determine the degree of blood cell contamination in GC preparations; to assess techniques of GC purification; and to determine possible effects of contaminating cells and purification techniques on cultured GC in terms of steroid hormone production. DESIGN: Contamination of GC by white blood cells was assessed by Wright's stain and immunohistochemistry. Purification was attempted by: (1) Ficoll density centrifugation (to remove polymorphonuclear leukocytes [PML]); (2) incubation in tissue culture plastic dishes (to remove adherent monocyte/macrophages); and (3) incubation in the presence of high salt (to remove lymphocytes). RESULTS: Ficoll density centrifugation reduced PML to 2% of total cells, incubation in plastic dishes reduced monocyte/macrophage contamination from 6% to 7% down to less than 1%, and high-salt incubation reduced lymphocyte contamination from 10% to 12% down to 4%. Granulosa cells plated after preparation with addition of high salt showed increased progesterone production, which could not be entirely explained by the removal of contaminating lymphocytes. CONCLUSION: These results indicate that the human GC culture system is more complex than is often assumed, and methods that remove a majority of these white blood cells are presented. PMID- 1936323 TI - Mitogen(s) for endometrial-like cells can be detected in human peritoneal fluid. AB - OBJECTIVE: To characterize the presence of mitogen(s) in the peritoneal fluid (PF). DESIGN: Aliquots of PF aspirated at laparoscopy were assessed for mitogenic activity by the rate of [3H]-thymidine incorporation into the deoxyribonucleic acid of various cell lines. SETTING: Peritoneal fluids were obtained from patients having a laparoscopy for the investigation of infertility or pelvic pain or for tubal ligation. PATIENTS: Seven women with laparoscopic evidence of endometriosis (stage I and II) and six without evidence of endometriosis. INTERVENTION: None. MAIN OUTCOME MEASURE: After 24 hours of culture in absence of serum, NIH/3T3 mouse embryo fibroblasts, (KLE) human endometrial adenocarcinoma cells, and primary cultures of rabbit endometrial cells were incubated in the presence of appropriate amounts of PF or bovine serum albumin (control) for 22 hours before adding the [3H]-thymidine for 2 hours. RESULTS: Aliquots of PF containing greater than 100 micrograms/mL total protein concentration stimulated the proliferation of all cell types. This mitogenic effect was dose-dependent and was greatest on endometrial-like cells. The mitogenic activity was fully recovered after adsorption on dextran-coated charcoal and was sensitive to tryptic digestion and to heat. It could not be retained on cartridge of C18 silica and was calculated to have a molecular weight greater than 30,000 by gel permeation chromatography. CONCLUSIONS: Peritoneal fluid from women with or without endometriosis contain growth factor(s) that are proteinaceous in nature and capable of stimulating the proliferation of endometrial-like cells and fibroblasts. These mitogens could play a role in the pathogenesis of endometriosis. PMID- 1936324 TI - Deficient antiendometrium lymphocyte-mediated cytotoxicity in patients with endometriosis. AB - OBJECTIVE: To study the possible role of the immune system in the pathogenesis of endometriosis. DESIGN: A cytotoxicity assay by 51Cr release was performed to determine the lymphocyte cytotoxic response toward endometrial targets and an erytroleukemic cell line (K562). SETTING: The assays were performed in an academic research environment. PATIENTS, PARTICIPANTS: Twenty-five control women and 25 patients with endometriosis were selected on the basis of laparoscopic examination. INTERVENTIONS: The lymphocyte cytotoxic activity was evaluated separately on endometrial stromal and epithelial cells after 4 hours' incubation. MAIN OUTCOME MEASURE: The study was designed to determine, in controls and endometriosis patients, the lymphocyte-mediated cytotoxicity toward stromal and epithelial cells of endometrium. RESULTS: The lymphocyte response in the presence of stromal cell antigens was significantly lower (P less than 0.02) in disease affected women when compared with that obtained in controls (2.89 +/- 0.87 and 7.64 +/- 1.66, respectively). In contrast, when the same assay was performed on K562 cells, no difference was observed between endometriosis patients and controls. CONCLUSIONS: These data suggest that an altered immune recognition might be one of the pathogenic mechanisms of endometriosis. Moreover, they indicate that this is not a general phenomenon but is specific for the endometrial target. PMID- 1936325 TI - Parthenogenetic activation and development of fresh and aged human oocytes. AB - OBJECTIVE: To develop a systematic study of the parthenogenetic activation and early development of human oocytes. DESIGN: Human oocytes (both freshly retrieved and remaining unfertilized after exposure to spermatozoa) were exposed to alcohol or calcium ionophore and examined for evidence of activation. SETTING: Academic research department of a teaching hospital. PATIENTS, PARTICIPANTS: Couples donating oocytes were undergoing therapy for infertility with in vitro fertilization or gamete intrafallopian transfer. INTERVENTIONS: Gonadotropin releasing hormone agonist and human menopausal gonadotropin were administered at therapeutic doses. MAIN OUTCOME MEASURES: After application of activation stimuli at varying doses and durations, oocytes were examined for evidence of meiotic reactivation, pronuclear formation, deoxyribonucleic acid content, and cleavage. RESULTS: Fresh and aged human oocytes can be activated parthenogenetically using a calcium ionophore but at lower rates than seen for mouse oocytes (typically 50% to 60% versus 90% to 100%, respectively). Ethanol was a poor activating agent (maximum activation rate 16%). Human parthenotes can complete division to the eight cell stage. CONCLUSIONS: These results indicate that parthenote embryos may provide a source of material to study changes that occur during early human development. The data also raise the possibility that some early human pregnancy losses may involve oocytes that have been parthenogenetically activated spontaneously. PMID- 1936326 TI - Heterogeneity in patient populations explains differences in in vitro fertilization programs. AB - OBJECTIVE: To evaluate the efficacy of in vitro fertilization and embryo transfer (IVF-ET). DESIGN: Two different models for pregnancy rates in IVF-ET have been developed: a beta-geometric model and a split population model. SETTINGS: All IVF cycles were performed at the Yale University School of Medicine in New Haven, Connecticut. PATIENTS, PARTICIPANTS: All patients undergoing 1,257 IVF-ET cycles performed between the years 1983 through 1987. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The probability of achieving a viable pregnancy per cycle. RESULTS: Because both models provide excellent explanations for our data distribution, the decline in the conditional probability of achieving pregnancy after a given number of unsuccessful cycles may be inferred. CONCLUSIONS: These findings question the justification of continuing IVF-ET treatment beyond some threshold number of cycles. PMID- 1936327 TI - Hypospadias after assisted reproduction incorporating in vitro fertilization and gamete intrafallopian transfer. AB - OBJECTIVE: To determine incidence of hypospadias in infants born as a result of assisted reproductive technology (ART). DESIGN: Prospective data collection. SETTING: Parents with various forms of infertility attended an in-hospital in vitro fertilization program. PATIENTS: Two of the 53 male infants, conceived as a result of ART over a 3-year period, were born with hypospadias. INTERVENTIONS: Patient no. 1 underwent follicular stimulation (17 ampules of human menopausal gonadotropin (hMG), followed by 10,000 IU of human chorionic gonadotropin (hCG) 60 hours after the last hMG). Patient no. 2 underwent follicular stimulation with clomiphene citrate 100 mg/d from days 3 to 7, followed by 14 ampules of hMG starting day 6, and 10,000 IU of hCG 30 hours after her last hMG. MAIN OUTCOME MEASURES: All infants were examined in the immediate postpartum period for congenital anomalies. RESULTS: Infant no. 1, one of a set of dizygotic twins, had penoscrotal hypospadias, with normal renal sonogram and chromosomal studies. Infant no. 2 had glandular hypospadias with the urinary meatus displaced to the border of the glans. CONCLUSION: This high incidence raises concern about possible links between assisted reproduction and hypospadias. PMID- 1936328 TI - Prevention of premature luteinizing hormone and progesterone rise with a gonadotropin-releasing hormone antagonist, Nal-Glu, in controlled ovarian hyperstimulation. AB - OBJECTIVE: To report a preliminary study on the efficacy of a gonadotropin releasing hormone antagonist (Nal-Glu) for preventing premature luteinizing hormone (LH) and progesterone (P) rise in controlled ovarian hyperstimulation using clomiphene citrate (CC) and human menopausal gonadotropin (hMG). DESIGN: Participants in the study formed two groups. Both groups received CC-hMG and Nal Glu. Group II differs from group I for receiving human chorionic gonadotropin (hCG) and blood samples for 10 days after the second Nal-Glu injection. SETTING: Centre de Fecondation in Vitro, Hopital Antoine Beclere. PATIENTS: Eleven women 25 to 34 years of age and having normal menstrual cycles using barrier method of contraception not attempting pregnancies participated in the study. INTERVENTION: Daily blood samples, pelvic ultrasound, and CC-hMG/Nal-Glu/hCG administration. MAIN OUTCOME MEASURES: (1) Spontaneous LH surge and P rise, follicular growth, and plasma E2 levels in cycles with CC-hMG/Nal-Glu administration and (2) luteal phase after hCG injection in subjects previously treated with CC-hMG/Nal-Glu. RESULTS: Plasma E2 level increased from 983 +/- 80 pg/mL (mean +/- SEM) on the day of the first Nal-Glu administration to 1,159 +/- 102 and 1,610 +/- 114 pg/mL (mean +/- SEM) 24 and 48 hours later. In 10 women, LH and P remained low for at least 96 hours after the first Nal-Glu administration. In one subject, plasma LH was already elevated at the time of the first Nal-Glu injection. In women who received hCG, plasma E2 and P reached a maximum of 1,258 +/- 313 pg/mL and 50.3 +/- 12.8 ng/mL (mean +/- SEM), respectively, on the 6th day of the luteal phase. CONCLUSION: Our results suggest that timely Nal-Glu injections can prevent LH and P rise for at least 96 hours, in spite of increasing levels of plasma E2. Moreover, Nal-Glu had no adverse effect on the kinetic of E2 rise, the follicular growth, or on the post-hCG hormonal profile. PMID- 1936329 TI - Antiovary antibodies, repeated attempts, and outcome of in vitro fertilization. AB - OBJECTIVE: To determine whether the microtrauma induced by repeated puncture of ovarian follicles could result in the production of autoantibodies in women submitted to in vitro fertilization (IVF). DESIGN: Antiovarian antibodies were assayed in serum samples obtained from women engaged in IVF and in serum samples from healthy controls. SETTING: Blood samples were obtained after oocyte collection in the local hospital's IVF unit. PATIENTS: One hundred ten women undergoing IVF entered the study. Oocyte division, numbers of embryos, and pregnancy were recorded for each woman. Control samples were from 40 individuals with no sign of autoimmune disorder. INTERVENTIONS: Antiovarian antibodies were assayed in indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) using human ovary as antigen. Specific immunoglobulin (Ig)G, IgA, and IgM were tested separately in an ELISA. MAIN OUTCOME MEASURE: Antiovarian antibody levels were compared between patients and controls and correlated with the subsequent results of IVF. RESULTS: Significantly higher levels of IgG, IgA, and IgM antiovarian antibodies were observed in the group of IVF women (P less than 0.001). IgM antiovarian antibodies correlated with a lower number of embryos (P less than 0.001) and IVF failure (P less than 0.05). CONCLUSIONS: These data suggest that ovarian trauma may lead to the production of autoantibodies. PMID- 1936330 TI - Total acrosin activity correlates with fertility potential after fertilization in vitro. AB - OBJECTIVE: To evaluate the possible relationship between total acrosin activity in spermatozoa and fertility potential after fertilization in vitro. DESIGN: Total acrosin activity of spermatozoa was measured in 101 in vitro fertilization (IVF) cases by an observer unaware of fertilization and cleavage results. SETTING: University Hospital is a tertiary referral center offering a government supported In Vitro Fertilization Programme. PARTICIPANTS: Participants were couples undergoing IVF. INTERVENTIONS: A miniature assay measured total acrosin activity in the semen sample used for IVF. OUTCOME MEASURES: The proportion of mature oocytes fertilized, the proportion of mature oocytes transferred, and fertilization of at least one mature oocyte were considered outcomes with fertility potential. RESULTS: Total acrosin activity correlated with both the proportion of mature oocytes fertilized and the proportion of mature oocytes that were transferred as cleaving embryos. Total acrosin activity was higher in cycles when one or more mature oocyte fertilized compared with cycles with failed fertilization of all mature oocytes. CONCLUSIONS: The likelihood ratio for subnormal results indicates that measurement of total acrosin activity is a fair test of the fertilizing capacity of sperm. PMID- 1936331 TI - Direct intraperitoneal insemination--clinical results and comparison between two methods of sperm preparation. AB - OBJECTIVE: To compare sperm preparation with a new self-migration method in sodium hyaluronate and a centrifugation/swim-up method and to study the efficiency of direct intraperitoneal (IP) insemination. STUDY DESIGN: Sodium hyaluronate and centrifugation/swim-up were used randomly for direct IP insemination in alternating cycles. Treatments were given with an interval of at least one untreated cycle. When ovulation occurred on weekends, the patients received only controlled ovarian hyperstimulation. SETTINGS: Department of Obstetrics and Gynecology University Hospital, Uppsala, Sweden. PATIENTS: Seventy nine couples with unexplained infertility (n = 53), endometriosis (n = 17), and cervical factor (n = 9). INTERVENTIONS: Controlled ovarian hyperstimulation was accomplished by clomiphene citrate and gonadotropins. MAIN OUTCOME MEASURES: Sperm parameters and pregnancy rates. RESULTS: Sodium hyaluronate and centrifugation/swim-up resulted in similar conception rates, but sodium hyaluronate recovered more motile spermatozoa than centrifugation/swim-up (P less than 0.0001). The number of patients who became pregnant after direct IP insemination or controlled ovarian hyperstimulation only was significantly higher than that observed after untreated cycles (P = 0.00001 and P = 0.008, respectively). CONCLUSIONS: Sperm preparation with sodium hyaluronate can be used as an alternative to centrifugation/swim-up. Direct IP insemination appears to increase the cycle fecundity, but whether direct IP insemination/controlled ovarian hyperstimulation is more effective than controlled ovarian hyperstimulation alone has yet to be proven. PMID- 1936332 TI - The effects of prolactin on human sperm capacitation and acrosome reaction. AB - OBJECTIVE: To study the effects of human prolactin (PRL) on human sperm capacitation and acrosome reaction. DESIGN: Acrosome reactions were induced by the addition of follicular fluid (FF) and progesterone (P). Experiments were performed to determine time and dose-dependent effects of PRL on sperm capacitation, potentiation of the acrosome reaction, decapacitating effects, and potential for PRL to induce an acrosome reaction. RESULTS: An average of 31.5% of spermatozoa underwent acrosome reaction with addition of FF and P. No time- or dose-dependent PRL effects on sperm capacitation or acrosome reaction were found (P greater than 0.05). CONCLUSION: Prolactin does not play an important role in human sperm capacitation or acrosome reaction. PMID- 1936333 TI - Immunomodulation in the treatment of endometriosis-associated subfertility: use of pentoxifylline to reverse the inhibition of fertilization by surgically induced endometriosis in a rodent model. AB - OBJECTIVE: To determine the effect of pentoxifylline on early reproductive performance in an animal model for endometriosis. DESIGN: Preclinical blinded study in a rodent model. SETTING: Animal research laboratory. PARTICIPANTS: Sexually mature female golden hamsters. INTERVENTIONS: At laparotomy, groups of hamsters were subjected to: (1) excision of the right uterine horn and (2) excision of the right uterine horn with explantation of four 2-cm2 uterine fragments onto the left uterine mesentery. Six weeks later, surgically treated hamsters and nonsurgically treated controls were subjected to ovulation induction with pregnant mare serum gonadotropin and human chorionic gonadotropin; subsequently, hamsters were divided into groups for periovulatory treatment with either pentoxifylline (2.5 mg/kg) or vehicle given subcutaneously every 8 hours. All hamsters were mated with proven males and killed after 48 hours. MAIN OUTCOME MEASURES: Numbers of unfertilized oocytes and embryos recovered from the left uterine horn at 48 hours after mating. RESULTS: Fertilization rates in surgical and nonsurgical control groups exceeded 90%. Fertilization was significantly impaired in saline-treated animals bearing uterine explants (mean of 2.3% +/- 1.9%). Administration of pentoxifylline dramatically reversed this effect (99.0% +/- 0.7% mean fertilization rate). CONCLUSION: These data suggest that periovulatory treatment with pentoxifylline abrogated the adverse influence of endometrial explants on fertilization in the rodent model. Periovulatory administration of nonteratogenic immunomodulatory agents may provide an alternative to conventional treatment for endometriosis. PMID- 1936334 TI - New technique for selective transcervical osteal salpingography and catheterization in the diagnosis and treatment of proximal tubal obstruction. AB - Transcervical fallopian tube catheterization to recanalize the proximal (uterine end) fallopian tube are rapidly gaining acceptance for the diagnosis and treatment of tubal obstruction. We describe a new simplified technique for performing this procedure. Our technique obviates the need for hysterocaths and assures delivery of an atraumatic spherical tip of a cannula to the uterotubal junction. Compared with other techniques, it is quick with no need for IV or paracervical anesthesia or analgesia, no cervical dilatation, nor the use of Hyskon nor CO2 insufflation devices. PMID- 1936335 TI - Transvaginal intratubal insemination by tactile sensation: a preliminary report. AB - Transvaginal catheterization of the fallopian tube has gained increased popularity for transfer of embryos and gametes. Forty-five ITIs were performed on 32 patients using the novel approach of tubal transfer via tactile sensation. This group of patients had undergone an average of 5.2 IUIs before ITI. There were a total of 11 pregnancies, 6 occurring with hMG stimulation and 5 with CC stimulated cycles (34% PR per patient). Three pregnancies ended with spontaneous abortion, and one patient developed acute salpingitis necessitating laparotomy. These data suggest ITI may be effective in assisted reproduction but, as other invasive procedures, is not without risk. PMID- 1936336 TI - Triplets or sequential siblings? A case report of three children born after one episode of in vitro fertilization. AB - To our knowledge, this is the first case report of three pregnancies resulting from the one batch of embryos. As the survival rate for cryopreserved embryos increases, there will be more families that will be able to be completed after just one cycle of hyperstimulation and oocyte collection, thereby making IVF-ET more cost-effective. PMID- 1936337 TI - What is the true follicular diameter: an assessment of the reproducibility of transvaginal ultrasound monitoring in stimulated cycles. PMID- 1936338 TI - Leuprolide acetate stimulates smooth muscle of the human reproductive tract. AB - Leuprolide acetate (10(-4) to 10(-5) M) had a stimulatory effect on spontaneous contractions of human myometrium and fallopian tube in vitro. The uterine and tubal tissues were from patients with dysfunctional uterine bleeding that was treated by hysterectomy. Whether the effect of LA on smooth muscle is a component of the mechanism of therapeutic action or an undesirable side effect remains to be determined. PMID- 1936339 TI - Absorption of micronized progesterone from a nonliquefying vaginal cream. AB - An improved delivery method to achieve sustained physiological P levels would be useful. Based on this single-dose pharmacokinetic study, micronized P prepared in a nonliquefying vaginal cream holds promise as a convenient method to achieve this goal with a single daily application. PMID- 1936340 TI - Presence of messenger ribonucleic acid for epidermal growth factor (EGF) and EGF receptor demonstrable in monolayer cell cultures of myometria and leiomyomata. AB - There is a paucity of data concerning the factors involved in the growth of uterine leiomyomata. The expression of mRNAs encoding EGF and the EGF receptor in myometrial and leiomyoma cultures suggest that EGF may be involved in the autocrine/paracrine regulation of human uterine leiomyomata and myometrial growth. PMID- 1936341 TI - [Why should teeth, used for anchoring partial prostheses, also be used as their support?]. AB - It is proved by means of static models that, as regards the load of the periodontium, the teeth employed for the dental supporting and anchoring of partial dentures are in a much more favourable situation than the teeth employed but for anchorage. Viz. while the resultant of the axially and laterally directed forces resulting from supporting and anchoring does not become eccentric, the direction of the but anchorage force points out of the structure and entails an unfavourable torque on the tooth. PMID- 1936342 TI - [Reconstruction of the maxilla by a microsurgical method and bone transplantation using bone from the scapula]. AB - For replacing partial lack of the upper jaw bone shoulder-blade transplanted by microsurgical method is used. The anatomy of the veins supplying the transplant and the surgical method are described. In connection with describing two cases good functional and cosmetic successes are reported on and the great importance of living bone replacement is emphasized. PMID- 1936343 TI - [Dental status of young recruits--in the light of the past 15 years]. AB - The tendency of the caries frequency and the caries intensity was intended to be described in our report. Our results were, essentially, concordant in the Hungarian professional literature while they significantly differed from the data published in western professional literature, especially as regards its course formation. Our results (also) signal that much yet remains to be done by both the civil and the dental care and prevention network of our country. PMID- 1936344 TI - [A case of maxillofacial gunshot wound complicated by acute hemorrhage from the internal carotid artery and the internal jugular vein]. AB - A complicated case of a big vein injury associated with a maxillofacial gun-shot injury and its successful treatment are reported on. The course of the vein injury is explained and the significance of team work is emphasized. PMID- 1936346 TI - [20-years experience with tooth reimplantation]. AB - Tooth reimplantation experiences through 20 years are reported on. On basis of his results the tooth maintaining method is suggested to be employed by practicing dentists. PMID- 1936345 TI - [The effect of the transsection of the inferior alveolar nerve on neurogenic inflammation of the mouth mucosa. II. Immunohistochemical studies]. AB - The distribution of nerve fibers displaying calcitonin gene-related peptide (CGRP) immunoreactivity in the mandibular mucosa was studied in control rats, in rats after unilateral transection of the inferior alveolar nerve (IAN), and in animals following cervical sympathetic denervation. According to the results, the transection of the peripheral branch of the IAN has no effect on the distribution of the CGRP immunoreactive nerves. PMID- 1936347 TI - [The effect of ultrasonic therapy in rheumatoid arthritis of the temporomandibular joint]. AB - The mouth opening distance, the joint pressure sensitiveness and the biting strength have been measured. In the treated group all three examined parameters showed significant improvement while in the placebo group two parameters (pressure sensitiveness and mouth opening distance) changed significantly. The placebo effect collateral to the real therapeutic effect is not a rare phenomenon in physico-therapy. However, the real effect of the physico-therapeutic treatment can be judged only by means of double blind examination. PMID- 1936348 TI - [The effect of mouthwashes containing amino-fluoride and stannous fluoride on plaque formation and gingivitis in adults]. AB - The aim of the study was to assess the effect of amine fluoride (AmF)--stannous fluoride (SnF2) containing toothpaste and mouthrinsing on dental plaque accumulation and gingivitis. The examinations were performed on two groups of 20 (using AmF/SnF2)-, resp. 24 (using NaF) participants. The mean age was 45.6-, resp. 48.8 years. The duration of the study was five months. Toothbrushing was performed with standardized (multi-effect) toothbrushes, and after it mouthrinsing twice a day. Dental plaque was scored with the Plaque Index of Silness and Loe (1964) and gingivitis was assessed by the modified Sulcus Bleeding Index (Muhlemann and Son 1971) Plaque Index mean values showed a significant decreased in both groups (p less than 0.01). The reduction in the AmF/SnF2 group was more pronounced (63.7%) than in the NaF group (39.3%). The Sulcus-Bleeding Index mean values decreased also significantly in both groups (p less than 0.01). The decrease in the AmF/SnF2 group was 56.5% and in the NaF group 39.0%. CONCLUSION: in the course of a five-month's period AmF/SnF2 containing toothpaste and mouthrinsing had better clinical effect on plaque accumulation and gingivitis than NaF containing toothpaste and mouthrinsing. PMID- 1936349 TI - [Prosthetic implications of dental screening tests of adolescents]. AB - The 700 teen-agers of 14 to 19 years of age observed in the course of national dental screen tests between 1985 and 1989 showed 1198 edentulousness and 154 destroyed teeth. Dental appliances were prepared but for 33 juveniles which, in case of 14 persons, were covering crowns or pin teeth while with 19 thereof it were bridges. Thereby 3.25% of the existing deficiencies were replaced. Removable dentures have not been prepared at all although it would have been justified. PMID- 1936350 TI - [Significance of the angle of the CO2 laser beam, experimental studies in the oral cavity]. AB - In the mouth cavity of white rats the surface extension and depth of the defect brought about by laser beam arriving at various angles of incidence have been examined by means of hand- and operational microscopy and micro manipulator, respectively. In case of an angle of incidence of 90 degrees at the same energy, exposition time and focusing the forming crater is the deepest and the surface diameter the smallest. The more the angle of incidence of obliquely incident race deviates from 90 degrees, the more diminishes the depth of the lesion and increases its surface. Sparing of the surrounding healthy tissues and exact removal of pathological tissues at the surface and in the depth can best be obtained by a ray incident at 90 degrees. Thus, the operation not only spares the tissue but permits to keep the surrounding structures and, thus, the functions intact. Where an incidence at 90 degrees cannot be ensured by direct ray guiding, it is preferable to let the laser ray reach the tissue surfaces in a range of angles near 90 degrees. PMID- 1936351 TI - [Probing and occlusal caries]. AB - Occlusal fissures are one of the most frequent locations for dental caries. In order to detect early caries lesions in terms of "sticky fissures" tactile examinations with a sharp explorer are important parts of a classical clinical examination. The aim of the present investigation was to study whether probing with an explorer contributed to the development of occlusal caries in permanent of first molars. The study was carried out in 101 children (56 girls and 45 boys) who had intact pairs of first molars. Altogether 104 first molar pairs were studied. One and two years later both of the pairs were probed, but there was no significant correlation found between previous probing and occlusal caries. PMID- 1936352 TI - [Importance of periodic follow up of periodontal diseases for the maintenance of periodontal health and the longevity of dental restoration]. AB - The major objective of the author's investigation was to determine if the progression of attachment loss, the recurrence of active phase of periodontitis and development of new carious lesions can be controlled and prevented in individuals with prior history of aggressive periodontitis provided full mouth reconstruction and maintained at a proper level of oral hygiene. The results of a group on regular periodontal recall program were compared with the five years dental and periodontal findings on a matched group of patients having not been on regular maintenance program. The well maintained group of patients' annual recall data did not vary markedly. In five years basically the same amount of attachment apparatus was maintained. The reexamination of the non recall group at the end of the fifth year shoved a total deterioration of dentition due to the progression of periodontal disease and attachment loss. Especially those of rapidly progressing periodontitis cases shoved 70 to 100% attachment loss. This comparative study attempted to outline the insufficiency of our former dental philosophy of patient management and follow up. Authors emphasize the importance of the follow up, and maintenance of a very high level. PMID- 1936353 TI - [Experimental study of new embedding materials suitable for the casting of non precious metal alloys]. AB - In everyday practice hitherto used embedding masses permitted so to say but the making of shrinked castings. On basis of experiments performed with embedding masses (Bellavest, Castorit C) prepared for precious-metal-free alloys recently marketed it has been ascertained that exact castings can be prepared from moulds embedded therein if technical discipline is observed. PMID- 1936354 TI - [Caries status in diabetic patients]. AB - Clinical dental examination of 1600 diabetics (815 type 1 insulin dependent and 761 type 2 non-insulin dependent patients) has been performed according to the WHD criteria. According to examination results higher DMF mean value, less uncared of teeth with caries (D) and, in the age group of 19 years and above 30 years, more edentulousness has been found than with healthy individuals. The number of filled and crowded teeth (F) below the age of 35 years in diabetics (p 0.0001), above 45 years in the control group (p 0.0001) was higher. Concerning cared of teeth there was no deviation in the number of filled teeth between diabetic and healthy individuals whereas the number of crown covered teeth was higher with diabetics. (p 0.01). As to the distribution of individuals with healthy teeth and toothless ones it was found characteristic that while among diabetic individuals but 1%, in the control 1.4% possessed retained healthy teeth. The number of completely toothless individuals was higher (11.83%) with diabetics than with healthy individuals (2.25%). PMID- 1936356 TI - 1991 critical choices survey. PMID- 1936355 TI - [Dental education in the United States and Canada]. PMID- 1936357 TI - Master's program. PMID- 1936358 TI - Scheduling clinical space. PMID- 1936359 TI - Flexible scheduling. PMID- 1936360 TI - What's important to critical care nurses? PMID- 1936361 TI - A collaborative teaching model. AB - In the first 4 years of the program, more than 1500 individuals have attended and approximately 90% have successfully completed the course. Because of the success of this program, GCOI is contemplating other collaborative efforts. This model of collaboration could easily be instituted by hospitals in other large cities to provide a high-quality continuing course in a cost-effective and time-efficient manner. PMID- 1936362 TI - Effect of backrest position on pulmonary artery pressure and cardiac output measurements in critically ill patients. PMID- 1936363 TI - Standards of care. PMID- 1936364 TI - Being on the "wrong end" of critical care. PMID- 1936365 TI - Critical care nurses' perceptions of the confused elderly patient. PMID- 1936367 TI - Measurement of the thermoregulatory response: a review. PMID- 1936368 TI - Nursing management of "auto-PEEP". PMID- 1936366 TI - Neurocysticercosis and nursing implications. AB - Neurocysticercosis causes significant neurologic morbidity and mortality in many countries and is increasing in frequency in the United States. The disease should be considered in any patient who has lived in or traveled to an area where it is endemic and who presents clinically with signs of increased intracranial pressure, stroke, seizures, or other neurologic deficits. Neurocysticercosis can be a life-threatening disease depending on the size, location, and active or inactive status of the cysts. Neurocysticercosis is treatable both medically and surgically according to symptoms. The sooner the correct diagnosis is made, the greater the chances for recovery and prevention of further neurologic deterioration. The nurse who is knowledgeable about the cause and treatment for neurocysticercosis can assist in controlling the incidence of this disease, decreasing complications, and averting needless mortality. PMID- 1936369 TI - Marathon certification fair--an alternative method for annual skills certification in the critical care unit. PMID- 1936370 TI - Intrahospital transport of critically ill adults: potential physiologic changes and nursing implications. PMID- 1936371 TI - Child care demand and labor supply of young mothers over time. AB - This paper uses panel data from the National Longitudinal Survey of Youth (NLSY) to analyze jointly fertility, employment, and child care decisions of young women over time. As these young women age (from 21 to 25 years on average) they become increasingly likely to have young children, to be employed, and to use non relative forms of child care. A multivariate analysis reveals that rising wage rates and changes in household structure are important determinants of these upward trends. Further analysis reveals a considerable amount of movement each year among states defined by the presence of young children, employment, and child care arrangement. Overall the young women in the NLSY can be characterized as being in a volatile stage of their lives, when many economic and demographic factors are changing. They appear to respond to these changes by altering their labor supply and child care behavior. PMID- 1936372 TI - Wife or Frau, women do worse: a comparison of men and women in the United States and Germany after marital dissolution. AB - Longitudinal data from the Panel Study of Income Dynamics and the German Socio Economic Panel show that in the Federal Republic of Germany, women experience even sharper drops in economic status immediately after a marital split than in the United States, while German and American men fare about the same. German social policy does little to reduce the disparities. PMID- 1936373 TI - Remarriage patterns among recent widows and widowers. AB - Remarriage is one of the most important determinants of physical and economic well-being among the widowed. The goal of this study is to estimate how hazard rates for remarriage vary among widows and widowers on the basis of both observable and unobservable characteristics. The remarriage estimates rely on nationally representative samples of widows and widowers from the Panel Study of Income Dynamics. Continuous-time hazard rate regressions indicate strong age and duration dependence effects for middle-aged widows and widowers and for older widowers. Among middle-aged widows, blacks and those with dependent children in the home have lower rates of remarriage. For middle-aged widowers, living in urbanized areas limits the prospects of remarriage. For older widowers, education and, to some extent, economic status appear to have positive effects on the remarriage rates. Overall, age and time since widowhood have the strongest and most consistent effects on remarriage rates for different widowed groups. PMID- 1936374 TI - A longitudinal analysis of household and nonhousehold living arrangements in later life. AB - Most explanatory models of living arrangements in later life link the decision process surrounding choice of living arrangement to personal resources such as income and health. Applications of these models, however, are based for the most part on cross-sectional rather than longitudinal data. In this paper we examine living arrangements in later life among the nonmarried population aged 55 and over, using data from the Survey of Income and Program Participation. We observe individuals as they change living arrangements, die, or become institutionalized. Our results suggest that economic resources dominate the decision-making process in transitions across different household arrangements, whereas health is most important in explaining institutionalization. PMID- 1936375 TI - Correlations between frequencies of kin. AB - Recent years have seen the development of formal and microsimulation models of the structure and dynamics of kin networks. These models generally assume uncorrelated fertility within and across generations. Several sets of real data, however, show positive correlations between the frequencies of various categories of kin. This paper uses formal models to calculate the correlations that will exist between certain categories of kin even if mothers and daughters have independent fertility. Mechanisms by which fertility might be transmitted from mothers to their daughters are considered and the implications for kin correlations are evaluated. PMID- 1936376 TI - The new census question about ancestry: what did it tell us? AB - In addition to specific inquiries about race and Spanish origin, the censuses of 1980 and 1990 included an open-ended question about ancestry, which replaced the question about parents' place of birth that had been used since 1870. This paper examines findings from the new ancestry question from the perspective of measuring ethnicity. The question adds little information about Hispanics, racial minorities, or recent immigrants, who can be identified readily on the basis of other census inquiries. The ancestry question allows us to characterize the descendants of European immigrants, but because of ethnic intermarriage, the numerous generations that separate present respondents from their forebears, and the apparent unimportance of ancestry to many whites of European origin, responses appear quite inconsistent. In regard to these groups, we may now be in an era of optional ethnicity, in which no simple census question will distinguish those who identify strongly with a specific European group from those who report symbolic or imagined ethnicity. PMID- 1936377 TI - Variations on two themes: racial and ethnic patterns in the attainment of suburban residence. AB - To investigate racial and ethnic diversity in suburbanization, we draw on two complementary theoretical traditions, which we label "assimilation" and "stratification." Our analytic model is multilevel, and includes variables characterizing individuals, households, and metropolitan contexts. We use it to analyze the determinants of suburban versus central-city residence for 11 racial/ethnic groups. The analysis reveals that family status, socioeconomic, and assimilation variables influence the suburbanization process rather consistently. We take this finding as evidence in favor of the assimilation model. These effects display group variations, however, in a manner predicted by the stratification model. There are also suburbanization differences among metropolitan areas, particularly related to the relative economic status of cities and their suburbs, and between the northeast/north central regions and the south/west. Finally, we conclude that suburbanization is variable across the groups in a way that is not captured by broad categories such as "Asian" or "Hispanic." PMID- 1936378 TI - Movement toward stability as a fundamental principle of population dynamics. AB - Although convergence to stability is typically a complex and irregular process, the Kullback distance provides a measure that moves consistently to 0 as a population becomes stable. The roots of the Kullback distance are in information theory, but it is a meaningful demographic quantity. It reflects a population's log momentum, or the amount of growth built into a population's nonstable age distribution. The rate at which the Kullback distance moves toward 0 is neither constant nor monotonic. At any point in time, however, it decreases by the covariance between a population's age-specific growth rates and its log momentum. Although the present findings are couched in terms of movement toward stability, they are generally applicable because they relate to the behavior of any population at any instant. It is a fundamental principle of population dynamics that a population is always moving toward the stable population implied by its prevailing fertility and mortality rates, and that the extent of its movement is determined by the covariance between its age-specific growth and its log momentum. PMID- 1936379 TI - Fertility decline in Taiwan: a study using parity progression ratios. AB - Taiwan's decline in fertility is studied by using period parity progression ratios. Levels of marriage and motherhood are found to have been high and essentially constant though the late 1980s, suggesting that the decline has been due almost entirely to declines in second and higher order-births. Families with three or more children play an important role in maintaining the current level of fertility. The level of fertility would be even lower without these families. They contributed more than one-half child per woman to the total fertility rate during most of the 1980s. Total fertility rates computed from the period parity progression ratios indicate a substantially higher level of fertility than the conventional total fertility rate; they remained above or at replacement level through 1988. A formal demographic analysis suggests that the conventional total fertility rate has been depressed by shifts in age at childbearing. PMID- 1936380 TI - Dental caries: selected factors of children at risk. AB - This article reviews the dental caries risk factors of children by using an epidemiological model which has three interrelated factors--agent, host, and environment. Dental caries agent factors include microorganisms with cariogenic potential; host factors include gender, race, tooth arrangement, sugar consumption, knowledge, attitudes, and behaviors; environmental factors include type of community (rural vs. urban), socioeconomic status, use of dental services and fluoride. This article reviews these selected dental caries risk factors and describes how dental assistants can practically apply this information. PMID- 1936381 TI - Dental auxiliaries wanted! Please apply. AB - This paper reviews changes over the last decade in the numbers and demographic characteristics of dental auxiliary students, as well as changes in levels of financial compensation for dental auxiliaries. Responding to dental team workforce shortages reported by dentists across the nation, the ADA, state and local dental and dental team organizations have been working to promote recruitment and retention programs for dental assisting dental hygiene, and laboratory technology. By now you have heard about it, read about it, and probably have been part of it. Dental practices are changing and dentists are eagerly seeking increasing numbers of auxiliaries. But in reality, fewer and fewer dental assistants, dental hygienists, and dental technicians are available, and that situation is unlikely to change. An earlier series of reports in The Dental Assistant reviewed auxiliary training programs, salaries, changing working arrangements, and related developments occurring in the 1970s through the mid 1980s. The following presentation updates this review through 1990 and continues to emphasize the dwindling numbers of dental auxiliaries and their lack of adequate financial compensation. PMID- 1936382 TI - Recall visits--finding the right formula. PMID- 1936384 TI - 1966-1991: 25 years of learning experiences. PMID- 1936383 TI - Dentistry and stress. PMID- 1936385 TI - [Handling and experimenting with a new light curing material]. PMID- 1936386 TI - [Aspects of occlusal surface hygiene. Less is sometimes more]. PMID- 1936387 TI - [Investigation of fracture resistance of full porcelain crowns]. PMID- 1936388 TI - [Some theoretical bases for selection of an articulator system]. PMID- 1936390 TI - [Restoration of a maxilla. Preparation of secondary portion]. PMID- 1936389 TI - [On the introduction of new materials and procedures]. PMID- 1936392 TI - [Finishing procedures with Ivocap system]. PMID- 1936393 TI - [Genotype in dental function morphology]. PMID- 1936391 TI - [Vacupal system. Results of reduction of air quantity]. PMID- 1936394 TI - [Quicker and easier work dreams, that can be attained]. PMID- 1936395 TI - [Influences on quality and properties of dental cast titanium]. PMID- 1936396 TI - [My experiences with preparation of cast gold inlays]. PMID- 1936397 TI - [A practical layering technique. Demonstration of a patient case]. PMID- 1936398 TI - [Complete denture using APF-system]. PMID- 1936399 TI - [Variations in full porcelain. Possibilities and probable impossibilities]. PMID- 1936400 TI - [Easily-made bridges using Probond system]. PMID- 1936401 TI - [Restoration of posterior teeth with porcelain inlays or onlays]. PMID- 1936402 TI - [FGP technique--functionally generated path]. PMID- 1936403 TI - [Titanium--present status of a new dental material]. PMID- 1936404 TI - [Individuality versus mass production in manufacture of denture attachments]. PMID- 1936405 TI - [Complete denture using APF-system]. PMID- 1936406 TI - Prevention of craniofacial injuries in ice hockey. AB - Prior to 1975, craniofacial injuries were the most frequent of all ice hockey injuries. Through the cooperative efforts of hockey administrators, health professionals, sports standards organizations, and the introduction of mandatory protective equipment playing rules craniofacial injuries in youth, high school, and college hockey players in the United States have been almost eliminated. Blind eye injuries, once a major problem, no longer occur in players wearing certified full face protectors. The saving in health care costs for treating eye injuries alone is estimated to be upwards of $10 million annually. Despite the phenomenal success of amateur hockey organizations in eliminating most craniofacial injuries, such injuries continue to occur in recreational, "Old Timers," major junior, and professional hockey players because of failure to use the most effective types of protective equipment. The system established in the United States for preventing craniofacial injuries in the sports of ice hockey that involves youth, high school, and college hockey associations along with standards setting and certification procedures can serve as a model for all amateur sports throughout the world. PMID- 1936407 TI - Techniques for mouthguard fabrication. AB - The use and efficacy of mouthguards for the prevention of traumatic athletic injuries to the teeth and oral soft tissues as well as in the prevention of concussions should indicate to the athletic community the importance of this piece of protective equipment. By comparison to other athletic equipment, mouthguards are quite inexpensive. The underlying theme is to emphasize that for maximum comfort and protection, every athlete should possess a properly fitted mouthguard fabricated exclusively for the individual by a dentist. The materials and standard techniques used for the fabrication of stock, mouth-formed, and custom-made protectors are described. The characteristics that an ideal mouthguard should possess suggest that custom-formed mouthguards are superior in quality to either the stock or mouth-formed types, although the custom-formed types are more expensive and require the services of a dentist. The development of new dental materials has provided dentists with the opportunity to explore new techniques for the fabrication of custom-made mouthguards. New techniques for photopolymerized urethane diacrylate lipguards and mouthguards have been developed as have adaptations for those athletes who wear fixed orthodontic appliances and those who are partially edentulous. Proper cleaning and storage of all types of mouthguards can prolong the length of service of these protective appliances. PMID- 1936408 TI - Spin-off applications of mouthguards. AB - The spin-off applications of mouthguards are many and varied. Their uses range from protective to therapeutic and span all areas of medicine and dentistry. The designs range from simple minor modifications of the soft athletic mouthguard to sophisticated adaptations containing gears or electric switches. Their creative applications have provided relief to the cancer patient, increased independence to the handicapped and limited mobility patient, protection to the dentition of the patient undergoing general anesthesia, relief for the TMJ syndrome sufferer, and decreased risk of damage to the teeth and palate of the intubated infant, to name only a few. The adaptations and applications of this simple device are inspired by the needs of the patient and limited only by the imagination of the provider. PMID- 1936409 TI - The role of the sports team dentist. AB - In all, there is much to be done in the field of sports dentistry. Participation by the dentist can be very rewarding, not only for the good will generated, but for the personal satisfaction derived when it is realized that the dentist has not only treated the injured athlete, but may have prevented many more potential injuries from occurring. PMID- 1936410 TI - Diagnosis and management of sports-related injuries to the face. AB - The face is often the most exposed part of the body during athletic competition. This article concentrates on sports-related injuries to the zygoma and periorbital area, the maxilla, the nose, and the external ear. Discussions of the management of soft-tissue injuries and the diagnosis and treatment of underlying disruption of bone and cartilage are presented. A new piece of protective athletic equipment for the prevention of facial injuries to baseball players is introduced. PMID- 1936411 TI - Practical clinical applications of sports dentistry in private practice. AB - Preparing a practice to become "trauma-ready" involves more than educating the dentist and the staff in the proper management of dentofacial trauma. All members of the office should understand their roles in preventing and treating trauma. They must be willing to provide care after hours when called upon to do so. Dentists who want to be more involved might wish to volunteer their services as sports dentists for local school or recreational league teams. The dentist who is conscious of his or her patients who are at risk for sports-related trauma will also find others in the practice who might benefit from many of the same protective devices that are being constructed for athletes. These include children involved in higher-risk activities, developmentally disabled patients, patients undergoing general anesthesia, and others. Being trauma-ready may open up several rewarding activities for the practice because of the many spin-off applications. The trauma-ready practice must also be cognizant of the some-times perplexing legal and insurance issues with regard to preventing and treating sport-related injuries. In addition to lowering the risk exposure to the practice, the dentist can help ensure the maximum third-party benefits for the patient. PMID- 1936413 TI - Legal considerations in sports dentistry. AB - The professional duties and responsibilities of a dentist in the examination or treatment of an individual engaged in a program of exercise or organized professional or amateur sports are consistent with the dentist's professional duties and responsibilities to any patient. However, because sports activities present risks not usually encountered by the average patient the dentist's concern for the well being of the patient is to a degree modified and expanded. These new professional duties and responsibilities translate into new legal duties and responsibilities, and the dentist's legal risks in the treatment of these patients increase. Added to the general rules of compliance with the law, duties that flow from the doctor-patient relationship, recordkeeping, history taking, obtaining informed consent, Good Samaritan Laws, and confidentiality are those that apply to the law of sports dentistry. Because most dentists, knowingly or unknowingly, treat patients engaged in some form of sport activity or exercise, all should become familiar with the special legal issues that attach to treating these patients. PMID- 1936414 TI - Professional responsibility in sports dentistry. AB - Our professional responsibility related to sports dentistry extends beyond the office. By our active involvement in continuing dental education, we can become more knowledgeable in this relatively new area of sports dentistry. Although it is still in its infancy, sports dentistry is an ever-expanding field. As dentists in practice, whether as general practitioners, specialists, academicians, or researchers, each one of us has a professional responsibility to become involved. Sports dentistry is certain to be a part of our future. PMID- 1936412 TI - Implications of smokeless tobacco use in athletes. AB - After almost falling into obscurity, smokeless tobacco use began to increase almost simultaneously with the reduction in cigarette smoking that was influenced by the Surgeon General's first Report on Smoking and Health in 1964. Consumption of smokeless tobacco was stimulated by media promotion using professional athletes; and large numbers of impressionable male teenagers, assuming that it was a safe alternative to smoking, began to use this product, particularly snuff. The nicotine content of smokeless tobacco is equivalent to that of cigarettes and, therefore, will produce habituation and addiction. It may also expose the long-term user to a number of adverse physiologic effects on the cardiovascular system that are similar to those attributed to smoking. Smokeless tobacco contains N-nitrosamines that have a potential carcinogenic effect on the tissues with which they come into contact in the oral cavity. A hazard of short-term use is irreversible gingival recession. The contact of snuff with the oral mucosa can produce leukoplakia that is readily visible and will alert the dentist. The dental professional team must actively strive to prevent initiation of smokeless tobacco use and assist with cessation of this habit. PMID- 1936415 TI - Your dental laboratory's lease. PMID- 1936416 TI - Stereotactic removal of foreign bodies in the maxillofacial area. AB - A technique is described for making it possible to localize any deep-seated radiopaque foreign body in the soft tissues and skeleton of the maxillofacial area. Using a stereotactic guide system, any point in the facial skeleton can be reached exactly, with precalculated precision, from any point outside the face. Thus, a foreign body can be exposed and subsequently removed by a surgical approach that gives minimal discomfort and carries low risk. The target probe serves the surgeon as a guide bar whilst the tissue is dissected. A precondition of successful stereotactic operations in the head and neck area is close cooperation between neurosurgeons and maxillofacial surgeons. PMID- 1936417 TI - Evaluation of a new type of high sharpness film for skull radiography. AB - A new type of high sharpness, high speed film was evaluated in combination with rare-earth screens for modulation transfer function, root-mean-square granularity and characteristic curve, and compared with currently available film-screen combinations. The clinical applicability of the new system was also compared on the basis of resolution and the discrimination of anatomical features on radiographs of a skull phantom. The results indicated that the new type film provided a radiograph of higher image quality while at the same time reducing patient dose by about 20% compared with the present rare-earth screen systems, or with no loss of image quality while reducing patient dose by about 50% compared with the present calcium tungstate system. PMID- 1936418 TI - Recurrence of chondromyxoid fibroma: a case report. AB - A case of recurrence of a chondromyxoid fibroma 3 years after its surgical removal is presented. The significance of the clinical, radiographic and histological appearances is discussed. PMID- 1936419 TI - Clinical application of computerized continuous-infusion pressure-monitored sialography. AB - The clinical application of computerized continuous-infusion pressure-monitored sialography using an aqueous contrast medium during the investigation of 296 salivary glands is described. A comparison between the pressure changes and the sialographic features revealed a significant (P less than 0.001) correlation between raised filling pressure (greater than 60 mmHg) and the presence of an obstructive lesion (stricture, mucous plug, sialolith). Occasionally a raised filling pressure was observed although the associated sialography films were normal. The sensitivity of the technique was 86.4%. It is concluded that the monitoring of pressure changes occurring during sialography can alert the clinician to the presence of high filling pressure and may also provide additional evidence of obstructive changes within salivary glands. PMID- 1936420 TI - Frequency of bilateral temporomandibular joint disc displacement in patients with unilateral symptoms: a 5-year follow-up of the asymptomatic joint. A clinical and arthrotomographic study. AB - Bilateral arthrotomography was performed in 50 consecutive patients with unilateral symptoms of disc displacement to evaluate the frequency of temporomandibular joint disc displacement in asymptomatic joints. Using well defined clinical criteria, there were no false-positive findings of either reducing or non-reducing discs. On the other hand, a risk of false-negative diagnosis of non-reducing disc was apparent. Sixty per cent of the patients had a non-reducing displaced disc in the asymptomatic joint. Most of these patients could recall a previous spell of discomfort from this joint. Severe or moderate deformation had taken place in non-reducing discs, while reducing discs were normal in shape or had, at most, a thickening of the posterior band. The duration of symptoms was significantly correlated with the degree of deformation in the symptomatic joints (P less than 0.01). Perforation was statistically, significantly correlated with disc deformation and, in symptomatic joints, hard tissue changes. Fifty-seven per cent of the asymptomatic joints with displaced discs developed pain following the onset of symptoms from the contralateral side, most within 2 years. Less than half of them were free of pain at the end of the 5 year follow-up period. In view of this tendency for an asymptomatic joint with a displaced disc to subsequently develop pain refractory to treatment, such a joint must be considered a weakened link in the craniomandibular system, vulnerable to changes in mandibular function such as, for instance, displacement of the disc on the contralateral side. PMID- 1936421 TI - Effects of niobium filtration and constant potential on the attenuation of dental X-ray beams by water. AB - Two half-wave, self-rectified dental X-ray units and two constant potential units were compared with respect to the attenuation of the X-ray beams by water. The effect of additional niobium filtration on the half-wave beams was also explored. Exposures were standardized to give the same values at a depth of 2 cm. The constant potential units gave values of relative exposure which fell within the range of exposures produced by conventional half-wave, self-rectified units. The addition of niobium as a filter material resulted in a reduction of surface exposure of between 10% and 12%, depending on the beam quality. The more penetrating beams resulted in relatively smaller exposure at the surface and gave relatively greater exposure at deeper levels. The addition of niobium resulted in an increase in relative exposure of 30.6% at 70 kVp and 10.7% at 90 kVp at a depth of 6 cm. There was a linear relationship between relative exposure and half value layer, both at the surface and at a depth of 6 cm. Regression analysis yielded r2 values of 0.925 at the surface and 0.919 at 6 cm (P less than 0.0005). This study has failed to show differences in attenuation due to niobium filtration and constant potential, other than might be expected from half-value layer. PMID- 1936422 TI - Radiographic quality and patient discomfort in sialography: comparison of iohexol with iothalamate. AB - We have compared the usefulness of a newly developed, low osmolality contrast medium, Omnipaque 350 (75.49% iohexol, 350 mgI ml-1), for sialography with one of the established, Angioconray (80% sodium iothalamate, 480 mgI ml-1), in a double blind, prospective randomized clinical trial in 80 patients. The diagnostic quality of the sialograms, pain during the procedure and discomfort subsequently were investigated. There was no difference in either group between the number of sialograms judged as diagnostically useful, although those of excellent quality were significantly more frequent in the Angioconray group. The level of pain on injection of the medium was significantly lower in the Omnipaque group. Eighteen per cent of the patients with Omnipaque had severe or moderate pain on injection of the contrast medium, while 63% had such pain with Angioconray. There was no difference in postprocedural discomfort between the two contrast media. We concluded that the low osmolality contrast medium is more favourable for sialography despite its lower iodine content. PMID- 1936423 TI - Exposure factors and screen-film combinations in temporomandibular joint radiography. AB - Exposure factors and screen-film combinations providing optimal quality are identified for transcranial and transpharyngeal temporomandibular joint views, using conventional intra-oral radiographic equipment without grids. Standardized transcranial and transpharyngeal views, using a fixed whole cadaver head, were performed. Ten readily available screen-film combinations, ranging in nominal speed 20-600, were exposed over 40-100 kV. Films were blindly and independently order ranked by three observers on the basis of sharpness and contrast of cortical outline, trabecular detail, and visualization of adjacent bony structures. Preferred screen-film combinations as a function of kV, preferred kV levels for each screen-film combination, and overall ranking irrespective of kV or screen-film combination, were established. Accepting the use of the lowest radiation dose possible for diagnostically useful radiographs but imposing arbitrarily an upper limit of 20 mGy, it was found that exposures between 50 kV and 70 kV gave the optimal result for both techniques. The amount of scattered radiation in the emergent beam differs greatly between the two techniques. The most favoured combinations for the transpharyngeal technique used screens of fine resolution. Min-r/ortho M screen and film with nominal speed 40 at 60 kV gave 8.0 mGy skin dosage at 0.8 seconds exposure; the same combination at 50 kV was the most favoured, but with skin dosage calculated at 16.7 mGy for 3.0 seconds exposure. For the transcranial technique, medium speed screens providing better differentiation of scattered radiation beams and increased speeds were preferred. Most favoured for image quality was the Lanex Fine/T-Mat G combination at 60 kV giving 17.5 mGy skin radiation dose at 1.75 seconds exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936424 TI - Image salvage in panoramic radiography using histogram optimization. AB - Optical density and contrast recovery from poor quality panoramic radiographs was studied using the histogram modification technique. A series of experimental images of varying density and contrast were obtained by exposing a phantom in 4 kV steps between 50 and 94 kV. A standard of good image quality was selected by 10 observers grading the radiographs. Images were processed using the histogram specification technique and re-evaluated. All the processed images were found to be of acceptable quality. This technique was also shown to be applicable for salvaging unacceptable clinical radiographs. PMID- 1936425 TI - Age changes in oral structures. PMID- 1936426 TI - Helping anxious adult patients. PMID- 1936427 TI - The post dam. PMID- 1936428 TI - Dry socket: a painful post-extraction complication (a review). PMID- 1936429 TI - Understanding pathologists (an exercise in communication): 3. Understanding the report. PMID- 1936430 TI - Myopic excimer laser keratectomy. A preliminary report. PMID- 1936431 TI - Evolution of microsurgery. PMID- 1936432 TI - A new approach to lens epithelial cell removal: dispersion aspiration. PMID- 1936433 TI - Serum antibody levels to bovine corneal protein and polymethylmethacrylate intraocular lens after implantation. PMID- 1936434 TI - Evaluation of quality of cataract microsurgery. PMID- 1936435 TI - Excimer laser lens ablation via quartz fiber. PMID- 1936436 TI - Ocular inflammation after intraocular lens implantation. PMID- 1936437 TI - Effect of controlled continuous positive intraocular pressure by anterior chamber maintainer during cataract surgery on the incidence of pseudophakic cystoid macular edema. PMID- 1936438 TI - Refilling the lens with inflatable endocapsular balloon. PMID- 1936439 TI - Fibrin reaction and its cause. Prostaglandin E2--synthesis by residual lens epithelial cells. PMID- 1936440 TI - Nd:YAG laser diascleral cyclophotocoagulation: survival analysis after four years. PMID- 1936441 TI - Ciliary body excision in secondary glaucoma: a fifteen-year follow-up. PMID- 1936442 TI - Corneal rivets: a preliminary report. PMID- 1936444 TI - Rationale for the Salz Super Single blade for radial keratotomy. PMID- 1936443 TI - Focussed illumination of the retina visible through a partial air bubble after lens implantation. PMID- 1936445 TI - Wound healing after excimer laser photorefractive keratectomy. PMID- 1936446 TI - Eye-controlled microscope for surgical applications. PMID- 1936447 TI - Cataract extraction, posterior chamber lens implantation and pars plana vitrectomy with indirect ophthalmoscopy through the microscope. PMID- 1936448 TI - Computer simulation of the 'multifocal lens effect' after a keratorefractive procedure for the correction of myopia. PMID- 1936449 TI - Lamellar corneal grafting with autologous and homologous tissue. PMID- 1936450 TI - The coupling phenomenon and corneal transplantation. PMID- 1936451 TI - Corneal transplantation: is the prognosis improving? PMID- 1936452 TI - The UK cornea transplant service and the establishment of the David Lucas Manchester eye bank. PMID- 1936453 TI - Sodium hyaluronate in chemical burns. PMID- 1936454 TI - Nd:YAG laser cellular cleansing of intraocular lenses: results of ten consecutive patients. PMID- 1936455 TI - Laser phacolysis of the human cataractous lens. PMID- 1936456 TI - Bifocal implants: clinical results. PMID- 1936457 TI - The evolution of hydrogel implants. PMID- 1936458 TI - Secondary lens implants: experience, new techniques, and thoughts. PMID- 1936459 TI - Secondary lens implantation: a perspective. PMID- 1936460 TI - Use of heparin-modified lenses in high-risk cases for uveitis. PMID- 1936461 TI - Intraocular pressure during cataract surgery. PMID- 1936462 TI - Two years experience with transscleral fixation of posterior chamber lenses. PMID- 1936463 TI - Cataract surgery in eyes with colobomas. PMID- 1936464 TI - Hyperinsulinaemia is a predictor of non-insulin-dependent diabetes mellitus. AB - Most incidence studies indicate that baseline plasma glucose, either fasting or post-glucose load, is the best predictor of progression to non-insulin-dependent diabetes mellitus (NIDDM)--the higher the level, the higher the risk. Elevated serum insulin concentrations in the presence of normal fasting plasma glucose levels reflect the presence of insulin resistance and they have also been shown to predict deterioration to NIDDM in a number of populations. Hyperinsulinaemia is a notable characteristic of populations with a high prevalence of NIDDM such as Micronesian Nauruans, American Pima Indians, Mexican-Americans and Asian Indians. In Nauruans and Pima subjects with normal glucose tolerance, those with higher post-load (2-hour) serum insulin at baseline were more likely to progress to either impaired glucose tolerance (IGT) or NIDDM. Conversely, amongst subjects with IGT, progression to NIDDM was predicted by lower (but still high relative to normal) baseline insulin responsiveness. Similar results for subjects with IGT have been described in Japanese. It appears from longitudinal studies that baseline insulin and glucose levels explain much of the association of obesity with risk of NIDDM. It remains to be resolved whether obesity itself may be a manifestation of an underlying defect (such as primary hyperinsulinaemia) which leads to both obesity and NIDDM. The possible sequence of events for the development of NIDDM includes a genetic defect resulting in hyperinsulinaemia and/or insulin resistance and leading ultimately to secondary pancreatic exhaustion with an insulin secretory defect which may also be genetically determined or the result of glucotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936465 TI - Insulin-resistance and associated risk factors for coronary heart disease as seen in families. AB - Recent reports have shown that resistance to insulin-stimulated glucose uptake, increased plasma glucose and insulin response to oral glucose, and hypertriglyceridemia can be seen in first degree relatives of patients with type 2 diabetes. We have recently shown that very similar metabolic changes can be seen in hyperinsulinemic individuals who have either normal or impaired glucose tolerance (IGT). Given these data, we thought it would be of interest to compare the plasma glucose and insulin response to an oral glucose challenge, plasma lipid concentrations, and blood pressure in offspring of parents with IGT as compared to offspring of parents with normal glucose tolerance. Parents with IGT had higher plasma insulin and triglyceride levels and blood pressure than those with normal glucose tolerance. The two groups of offspring were young, non-obese and similar in terms of age, gender distribution and body mass index. Statistically significant increases in plasma insulin response to oral glucose and in systolic and diastolic blood pressure were present in the offspring of parents with IGT. Demonstration of similar abnormalities in plasma insulin response to glucose and blood pressure regulation in patients with IGT and in their offspring is consistent with the view that individual differences in insulin metabolism and blood pressure are modulated by genetic factors and that both may be related to variations in insulin-stimulated glucose uptake and/or plasma insulin concentration. PMID- 1936466 TI - Glucose metabolism in obesity and type 2 diabetes. AB - The aim of this review is to provide a comprehensive summary of the subject of glucose metabolism in normal and obese subjects, and in those with type 2 diabetes. The following topics are discussed: Glucose and insulin metabolism, including characterization of the role of various organs in maintaining glucose homeostasis in the basal state and after food. The action of insulin and the concept of insulin resistance, its main characteristics as revealed by studies of glucose metabolism in liver and skeletal muscle, the two organs primarily involved. Changes in insulin secretion in obese subjects and in diabetics are reviewed. Finally, the development of diabetes as a consequence of increasing insulin resistance in the obese diabetic subject is discussed. The principal features--insulin resistance, elevated free fatty acid levels and glucotoxicity- are emphasized. A possible explanation of how obesity leads to diabetes, emphasizing the role played by upper body fat distribution, is provided. PMID- 1936467 TI - Basal glucose metabolism in type 2 diabetes. A critical review. AB - In the current review we have re-evaluated the concept of markedly elevated basal glucose production rates in patients with Type 2 diabetes. Owing to underpriming of the enlarged glucose pool in hyperglycaemic Type 2 diabetic patients most previous studies using the primed-continuous tracer infusion technique may have markedly overestimated basal glucose production rates in proportion to the level of hyperglycaemia. Also previous studies using an adequate priming ratio may have overestimated glucose production to some extent due to assumptions of steady state conditions. Using adjusted priming and non-steady state calculations we have found near normal rates of basal glucose production and glucose utilization in obese patients with Type 2 diabetes. The presence of insulin resistance in these patients was confirmed using the euglycaemic clamp technique. Thus, it is suggested that the basal state in Type 2 diabetes may be considered as a compensated condition where glucose turnover rates are maintained near normal. Hyperinsulinaemia and hyperglycaemia may serve as compensating factors, compensating for the defects in insulin action. PMID- 1936468 TI - Cellular mechanism of metformin action. AB - Activation of the insulin receptor tyrosine kinase and tyrosine phosphorylation of intracellular substrates are important steps in insulin signalling. In order to elucidate the cellular mechanism of action of metformin (NN'dimethylbiguanide) we have focused towards the effects of metformin on the insulin receptor kinase, the phosphorylation cascade and the biological effect of insulin. Since annexins (lipocortins) have been recently recognized as substrates of several tyrosine kinases we have investigated the effect of metformin on phosphorylation of annexins after insulin stimulation or microinjection of pp60c-src kinase in Xenopus laevis oocytes. Insulin induced in oocytes progression through the cell cycle from late G2 to M phase (maturation). Microinjection of pp60c-src kinase or treatment with metformin potentiates both the rate and the level of insulin induced oocyte maturation. In oocytes prelabeled with 32P orthophosphate metformin potentiates insulin induced phosphorylation of annexins. It is concluded that annexins are substrates of the phosphorylation cascade initiated by insulin which is synergistic to the action of pp60c-src kinase and that this early phosphorylation events correlate well with the enhanced biological effect of insulin during metformin treatment. PMID- 1936469 TI - Metformin increases insulin-stimulated glucose transport in insulin-resistant human skeletal muscle. AB - The effect of metformin (0.1 mM) on glucose transport was investigated in healthy control and in insulin-resistant human skeletal muscle. Muscle samples (200-400 mg) were obtained from the rectus abdominis muscle (abdominal surgery) or from the vastus lateralis portion of the quadriceps femoris muscle (open biopsy technique) from 8 healthy controls (age 38 +/- 4 yrs, BMI 23 +/- 1) and from 6 insulin-resistant subjects (age 53 +/- 5 yrs, BMI 30 +/- 2). Metformin had no effect on basal or insulin-stimulated (100 microU/ml) 3-0-methylglucose transport in incubated muscle strips from healthy subjects. Muscle tissue from the insulin resistant group did not respond to 100 microU/ml of insulin (0.73 +/- 0.17 for basal and 0.81 +/- 0.22 mumol x ml-1 x h-1 for insulin-stimulation, NS). Basal glucose transport was unaffected by metformin, whereas insulin-stimulated (100 microU/ml) glucose transport was increased by 63% in the insulin-resistant muscles (0.73 +/- 0.17 in the absence vs 1.19 +/- 0.18 mumol x ml-1 x h-1 in the presence of metformin, p less than 0.05). In conclusion, metformin abolishes insulin-resistance in human skeletal muscle by normalizing insulin-stimulated glucose transport accross the muscle cell membrane. The mechanism for this effect remains to be elucidated. PMID- 1936470 TI - Erythrocyte glucose consumption in insulin-dependent diabetes: effect of metformin in vitro. AB - Erythrocyte glucose consumption in red blood cells from healthy donors or insulin dependent diabetics with stable glycemia was measured using the 2-deoxyglucose technique. Data showed that the formation of glucose-6P was severely impaired in diabetic red blood cells in both normo- and hyperglycemic incubation conditions. This defect seems to be inherent to the disease. Coincubation with Metformin (6.4 ug/ml) did not modify the G6P levels in RBCs from healthy donors and in RBCs from diabetics when incubated in normoglycemic conditions. However, when diabetics RBCs were incubated in a hyperglycemic medium, addition of Metformin strongly improved the intracellular levels of G6P. The underlying mechanism for the defect and the correction by Metformin remains to be determined. This study shows that also red blood cells may be involved in the failure of glucose homeostasis in diabetes and thus this may represent an additional target for therapy. PMID- 1936471 TI - The effects of metformin on the fibrinolytic system in diabetic and non-diabetic subjects. AB - Type II (non-insulin dependent) diabetes is associated with a high incidence of vascular disease that causes morbidity and mortality. The principal organs affected by this process are the heart, brain and lower limbs. For many years it has been proposed that depression of the fibrinolytic system, which acts to maintain patency of blood vessels, may contribute to the development of vascular disease. A number of pharmacological agents have been shown to enhance circulating fibrinolytic activity of which metformin is perhaps the most interesting because of its low incidence of serious side effects. Early studies with metformin demonstrated an increase in global fibrinolytic activity in patients with coronary artery disease, peripheral vascular disease and diabetes. Recent studies using assays specific for the components of the fibrinolytic system have shown that the effects of metformin are to cause a fall in plasma levels of the fibrinolytic inhibitor, plasminogen activator inhibitor-1 (PAI-1). There is evidence to suggest that the relationship between depressed fibrinolysis and vascular disease is due to high levels of PAI-1, and reasons to believe that a lowering of PAI-1 may be beneficial in this respect. Further studies are warranted to evaluate the long term effects of metformin warranted to evaluate the long term effects of metformin on the incidence of vascular disease in diabetic patients. PMID- 1936473 TI - Glucose and lipid metabolism in non-insulin-dependent diabetes. Effect of metformin. AB - Basal and insulin-mediated glucose and free-fatty acid (FFA) metabolism was evaluated in 6 non-insulin-dependent diabetic patients (NIDDM) previously treated by diet, before and after 4 week metformin treatment (850 mg twice/day). On both occasions, an euglycemic stepwise insulin (20 and 40 mU/m2/min) clamp was performed along with primed-continuous infusion of 3-3H-glucose and 1-14C palmitate and indirect calorimetry monitoring. FFA oxidation rate was measured from the rate of appearance of 14CO2. After metformin therapy, fasting plasma glucose, FFA, triglyceride, total cholesterol concentrations and HbA1c were all lowered (p less than 0.05-0.01) in the absence of any change in plasma insulin levels. Plasma FFA turnover rate (5.3 +/- 0.5 vs 3.9 +/- 0.8 mumol/kg/min; p less than 0.05) and FFA oxidation (0.93 +/- 0.12 vs 0.70 +/- 0.12 mumol/kg/min; p less than 0.05) were also lower after metformin treatment, while glucose oxidation increased from 0.9 +/- 0.2 vs 1.2 +/- 0.1 mg/kg/min. During the insulin clamp studies, whole body glucose disposal was higher both at the lower (2.1 +/- 0.4 vs 2.8 +/- 0.4 mg/kg/min) and higher insulin plateau (4.8 +/- 0.9 vs 6.3 +/- 0.9 mg/kg/min; p less than 0.01). Since no difference was apparent in glucose oxidation, the increase in glucose disposal was entirely accounted for by an improvement in non-oxidative glucose metabolism. Euglycemic hyperinsulinemia was followed by a reduction in plasma FFA concentration turnover rate that remained the same before and after metformin therapy. In conclusion, metformin treatment induces an improvement in glucose metabolism both in the basal and insulin stimulated state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936472 TI - Effects of metformin and glibenclamide alone and in combination on serum lipids and lipoproteins in patients with non-insulin-dependent diabetes mellitus. AB - Metformin, glibenclamide and their combination were compared in a randomized, double-blind trial in patients with non-insulin-dependent diabetes mellitus (NIDDM) using a parallel group design. The study was performed in primary health care, and the purpose was to assess possible synergistic effects of combination therapy with the two drugs as primary treatment versus conventional oral therapy, starting with one drug and adding the other, if necessary. Lipids and lipoproteins were measured in the study, and preliminary results are reported for one hundred sixteen patients concluding 6 months maintenance therapy. Comparison of mean differences showed that patients randomized to combination therapy (n = 60) demonstrated a greater decrease in total- and LDL-cholesterol levels after 4 and 6 months treatment than patients randomized to conventional therapy starting with either metformin (n = 28) or glibenclamide (n = 28). For LDL-cholesterol a significant difference was also found between patients solely on monotherapy with lower values after treatment with metformin. Triglycerides did not change significantly, and only minor fluctuations were seen in HDL-cholesterol, independent of treatment. Obese patients had significantly higher triglyceride concentrations than the non-obese group, both at baseline and after treatment, as well as significantly lower HDL-cholesterol levels. The mean triglyceride concentration (+/- SD) after 6 months treatment was 2.32 +/- 1.38 mmol/l in the obese group (n = 69) and 1.54 +/- 0.84 mmol/l in non-obese (n = 47). For HDL cholesterol the corresponding values were 0.83 +/- 0.23 mmol/l in obese and 0.93 +/- 0.29 mmol/l in non-obese patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936474 TI - Effects of metformin on dyslipoproteinemia in non-insulin-dependent diabetes mellitus. AB - A 12-week double-blind placebo-controlled trial to study the effects of metformin on lipoprotein concentration and composition was performed in forty patients with NIDDM and hyperlipoproteinemia. A significant decrease occurred in VLDL-apo B and all lipid components of VLDL, indicating a decreased number of circulating VLDL, while LDL-apo B was unchanged. Moreover in VLDL the relative TG content increased, the cholesterol content decreased, while in LDL the TG content decreased and the cholesterol content increased, indicating a change in the particle distribution over the spectrum VLDL-IDL-LDL. The initially enhanced TG content in HDL was reduced. While a reduction in VLDL is observed with all methods improving glucose control the observed compositional changes in VLDL and LDL have not been described before and may be a specific effect of metformin. PMID- 1936475 TI - Management of type 2 diabetes mellitus with special reference to metformin therapy. AB - As monotherapy, metformin is similar to the sulphonylureas, in improving both fasting and post-prandial plasma glucose levels by approx. 25-30%. Metformin, unlike the sulphonylureas, does not promote insulin secretion and does not cause weight gain and is therefore preferable in obese NIDDM. Metformin is also of benefit as combined therapy with a sulphonylurea, and in older subjects the two drugs may give as good glycaemic control as insulin. Lactic acidosis with metformin is less common than sulphonylurea-induced hypoglycaemia although the mortality risk is similar. However, where both groups of drugs are properly used clinically, serious side-effects are unusual. Metformin may have a potential advantage in the management of NIDDM with hyperinsulinaemia in that it does not increase insulin levels. Where insulin levels have been compared in the same type II patients, metformin can achieve similar glycaemic control as a sulphonylurea (gliclazide) but with significantly lower plasma insulin levels. PMID- 1936476 TI - The effects of oral hypoglycaemic drugs on serum lipids and lipoproteins in non insulin-dependent diabetes (NIDDM). AB - Coronary heart disease is a major cause of morbidity in NIDDM and is likely to be related to the abnormalities in serum lipids and lipoproteins commonly associated with it. The effects of treatment in general, and of oral hypoglycaemic drugs in particular, on serum lipids in NIDDM are not clear. In a cross-over study, the effects of 3 months treatment with metformin glibenclamide on body weight, blood glucose control, and serum lipoproteins were compared in 35 patients with NIDDM, inadequately controlled by diet alone. Glibenclamide alone increased body weight. Glibenclamide and metformin achieved equivalent blood glucose control, independent of initial body mass index. Neither drug affected serum triglyceride. Metformin significantly reduced low density lipoprotein cholesterol (mean change 0.34 mmol/1.95% confidence intervals -0.12 to -0.57 mmol/l, p less than 0.01). Neither drug altered high density lipoprotein or subfraction cholesterol. Changes in serum lipoproteins were also studied in 14 patients with NIDDM on long term metformin therapy, after 6 weeks placebo and again 6 weeks after restarting active drug therapy. Withdrawal of metformin resulted in a rise in fasting blood glucose, HbA1, serum total and low density lipoprotein (LDL) cholesterol. Restarting the drug reversed these changes. Multivariate analysis showed that serum total and LDL cholesterol varied with treatment, but not with glycaemic control. Metformin can therefore lower total and LDL cholesterol in NIDDM and this effect appears to be maintained long term. PMID- 1936477 TI - Comparative efficacy of metformin and glibenclamide in patients with non-insulin dependent diabetes mellitus. AB - Metformin and glibenclamide were compared in a randomized, double-blind trial in patients with non-insulin-dependent diabetes mellitus (NIDDM) using a parallel group design. The study was performed in primary health care, and the main purpose was to assess combination therapy with the two drugs as primary treatment versus conventional oral therapy. After a 2 months diet period patients were randomized to commence treatment with either metformin, glibenclamide or the combination of both. Patients randomized to monotherapy received the alternative drug in addition if the maximal dose i.e. 3 g metformin or 14 mg glibenclamide was insufficient to normalize the fasting blood glucose concentration (FBG). Randomization and dose escalation occurred at FBG greater than or equal to 6.7 mmol/l. The titrated dose was continued for 6 months, whereafter placebo was given for 2 weeks. Seventy-two patients were randomized to either the metformin group (n = 38) or the glibenclamide group (n = 34). Fifty-six completed 6 months treatment, twenty-eight in each randomized group. Glycaemic control was unchanged after diet alone in all groups. The improvement during drug treatment was highly significant (p less than 0.001), mean FBG difference (+/- SEM) 3.2 +/- 0.4 mmol/l and mean HbA1c difference (+/- SEM) 1.5 +/- 0.2% (n = 56). There were no significant differences between patients treated solely with metformin (n = 16) and glibenclamide (n = 17) or between patients treated with a combination of glibenclamide added to metformin (n = 12) and metformin added to glibenclamide (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936478 TI - Comparative three-month study of the efficacies of metformin and gliclazide in the treatment of NIDD. AB - In order to compare the effects of metformin and gliclazide on fasting serum insulin, 60 non-insulin dependent diabetics were included in a multi-centre study. Patients on a diabetic diet alone or a diabetic diet together with a sulphonylurea hypoglycaemic agent, with a fasting glucose greater than 1.4 g/l, on two measurements were included in the study. They were randomly allocated to two parallel groups and received either gliclazide or metformin. They were treated for three months and attended for consultation at one month and three months. The fasting serum insulin level decreased significantly in the group receiving metformin (26.2 +/- 3.2 mlU/L at entry versus 19.8 +/- 2.3 mlU/L after three months: less than 0.01), and increased in a non-significant way in the group receiving gliclazide (21.6 +/- 3 mlU/L versus 26.5 +/- 5 mlU/L after three months: NS). The difference between the two groups was significant (p less than 0.01). There was a comparable significant improvement in blood sugar levels during the three months in both patients receiving gliclazide and metformin. However, significant weight loss (p less than 0.05) occurred only in patients receiving metformin. There was an identical improvement in blood sugar control in both patients receiving gliclazide and metformin over the three months. On the other hand, fasting serum insulin levels decreased significantly in patients receiving metformin compared to gliclazide. The effect of metformin on serum insulin levels is probably due to its action on insulin resistance and its lack of effect on insulin secretion, in contrast to sulphonylurea hypoglycaemic agents like gliclazide. PMID- 1936479 TI - Prospective randomized two-years clinical study comparing additional metformin treatment with reducing diet in type 2 diabetes. AB - After a 2 weeks hospital treatment with a strong dietary regime 100 patients not sufficiently controlled (blood glucose fasting 120-180, pp 180-250 mg/100 ml), were randomly allocated to a purely dietary therapy or to a diet-metformin combination for a duration of 2 years. After 1 and 2 years the patients were rehospitalized for an accurate evaluation. Additionally, HbA1 was controlled every 3 months, in case of problems after shorter periods. If HbA1 exceeded 10% for more than 4 weeks the patients were hospitalized for 5 days in order to decide whether the deterioration of metabolic control was due to the patients' non-compliance to treatment or to treatment failure. During 2 years of observation 30 patients were withdrawn from the treatment for external reasons. 13 patients (6 diet, 7 metformin + diet) were non-compliant with diet, 3 further patients were not metformin-compliant. Therapeutic failures were confirmed in 4 diet patients, none of the metformin + diet patients failed to respond to treatment. After excluding all these patients there was a group of 29 diet and 25 metformin + diet patients with a similar development of criteria of metabolic control during 2 years. Lipid levels deteriorated in the dietary group more noticeably than during additional metformin treatment although without reaching a statistically significant level, though. The stimulated C-peptide was significantly reduced by metformin in comparison to diet only, which supports former findings of an insulin-lowering effect of the drug. PMID- 1936480 TI - Treatment strategies for secondary sulfonylurea failure. Should we start insulin or add metformin? Is there a place for intermittent insulin therapy? AB - Which therapy should be used in non-insulin dependent diabetes mellitus (NIDDM) with secondary sulfonylurea failure? Should we start insulin therapy, try a period of intensified insulin therapy and then switch back to sulfonylurea or should we add metformin therapy? To address this question, we have compared these three treatment strategies in 36 NIDDM patients who failed on treatment with sulfonylureas during a 6 month period. Insulin (short and intermediate-acting insulin before breakfast and dinner) and the combination of 21 mg of glibenclamide and 1.5 g of metformin resulted in an equivalent 30% improvement in glycemic control without significant effects on lipids. Intensified insulin therapy (6 weeks of intermediate and short-acting insulin 3 times daily), on the other hand, initially lowered blood glucose to the same degree as during the other two treatment regimes, but after switching back to sulfonylurea therapy (21 mg of glibenclamide/day) blood glucose concentrations returned to pretreatment values. Insulin therapy resulted in a 5 kg increase in body weight, 63% of which was accounted for by an increase in fat mass. Although body weight was unchanged during glibenclamide/sulfonylurea therapy, lean body mass and energy expenditure decreased significantly (p less than 0.05). Body weight and energy metabolism remained unchanged during intermittent insulin therapy. CONCLUSIONS: Despite similar blood glucose lowering properties, insulin and the combination of sulfonylurea and metformin have different effects on energy metabolism and body composition. Since these effects were not observed during treatment with sulfonylurea alone, they must be ascribed to metformin. PMID- 1936481 TI - Oral antidiabetic combination therapy with sulphonylureas and metformin. AB - In a multicentre trial in general practice, a total of 1823 type 2 diabetics, not adequately controlled by diet and maximal sulphonylurea therapy, were treated with additional metformin 850--2 550 mg/d for 12 weeks. The average postprandial blood sugar decreased from 15.48 mmol/l to 10.43 mmol/l, HbA1 fell from 11.0% to 9.1%. Serum triglycerides decreased from an initial level of 2.87 mmol/l to 2.41 mmol/l an mean total cholesterol from 6.76 mmol/l to 6.16 mmol/l. In addition, body weight and blood pressure declined steadily. All the described changes were statistically significant. The metformin-sulphonylurea combination therapy was generally well tolerated. Gastrointestinal side effects occurred in about 7% of patients, but mainly in the first week of treatment, generally disappearing spontaneous as therapy was continued. Side effects led to a discontinuation of the treatment in 4.2% of patients. PMID- 1936482 TI - Treatment of NIDDM patients with secondary failure to glyburide: comparison of the addition of either metformin or bed-time NPH insulin to glyburide. AB - In this study we compared, in 12 NIDDM patients with secondary failure to glyburide, the effect of adding either a single, low-dose bed time NPH insulin injection (0.2 U/Kg) or an oral metformin administration (500 mg x 3) to the previously ineffective sulfonylurea treatment. The addition of both insulin and metformin treatment significantly improved fasting plasma glucose, post-prandial plasma glucose and %HbA1. The effect of both combined therapies was already evident and maximal after 2 weeks of treatment. The addition of bed-time NPH insulin caused a greater decrease of fasting plasma glucose, although the difference with the addition of metformin was not significant. In contrast, the average post-prandial plasma glucose decrease was significantly greater after metformin addition. The addition of bed-time NPH insulin caused a significant increase in average body weight, while after metformin addition, average body weight was unchanged; no change in the average cholesterol and triglyceride level was observed after either combined therapies. PMID- 1936483 TI - Sulfonylurea-metformin-combination versus sulfonylurea-insulin-combination in secondary failures of sulfonylurea monotherapy. Results of a prospective randomized study in 50 patients. AB - 50 type II diabetics with secondary failure of a sulfonylurea (SU) treatment have been included in a randomised controlled trial by assigning them either to a Metformin + SU or insulin + SU treatment. At study entry the metabolic control of patients had to be insufficient, as demonstrated by increased fasting or postprandial plasma glucose levels (greater than 130 resp. greater than 180 mg/100 ml). The study lasted for a period of 12 months in which a Metformin treatment of 850, 1,700 or 2,550 mg/day or an insulin therapy of 12-40 IU was added to the existing maximal dose of SU. Both the Metformin and the insulin dosage were adapted to the response of metabolic control. Parameters of metabolic control and security were monitored regularly every two months. 16 patients in the Metformin + SU-group and 19 patients in the insulin + SU-group were observed for the total study period of 12 months. In both groups there was a similar development of metabolic parameters. Stimulated C-peptide reduced in both groups indicating an increase of peripheral insulin sensitivity under both treatment regimes. PMID- 1936484 TI - Insulin-resistance and lipoprotein abnormalities. AB - Resistance to insulin-stimulated glucose uptake is associated with an increased rate of synthesis and secretion of VLDL-triglycerides and, in the absence of adequate removal capacity, with hypertriglyceridemia. Subjects with a low glucose disposal rate or a high degree of insulin resistance (as measured by the euglycemic hyperinsulin clamp technique) have also decreased HDL cholesterol levels. The recent developments in the chemistry of lipoproteins indicate that the physicochemically defined lipoproteins such as VLDL, IDL, LDL or HDL are both chemically and metabolically heterogeneous. According to the Alaupovic concept, the plasma lipoprotein system consists of a mixture of particles, each of which is characterized by a unique apolipoprotein composition. Using enzyme-linked differential antibody immunosorbent assay and differential electroimmunoassay, we have discovered that the determination of lipoprotein particle profiles is essential for further clarification of the diagnostic value of measuring apo B and apo A-I. The metabolism of apo B and apo A-I containing lipoprotein particles seems to be affected primarily by their corresponding apolipoprotein composition. Some particular subpopulations of apo B containing lipoprotein particles, such as LpB containing only apo B, LpB:E containing apo B and (a) have been identified as important risk factors in atherosclerosis. We have also recently demonstrated that the protective effect of HDL is due to particles containing apo A-I but not apo A-II (LpA-I), while have little or have no effect those containing apo A-I and apo A-II (LpA-I:A-II). Non-insulin-dependent diabetic patients (NIDDM) are characterized by increased concentrations of cholesteryl ester rich LpB and triglyceride rich LpB:C-III and LpB:E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936486 TI - NIDD today. Proceedings of an international workshop. Helsingor, Denmark, September 7-8, 1990. PMID- 1936485 TI - BIGPRO (biguanides and the prevention of the risk of obesity): study design. A randomized trial of metformin versus placebo in the correction of the metabolic abnormalities associated with insulin resistance. AB - There seems to be a cluster of potentially atherogenic and diabetogenic abnormalities in subjects with central adiposity (high waist to hip ratio) and insulin resistance. To test whether reversing insulin resistance could lead to decreased vascular and diabetic risks, a trial using a drug to complement life style modification measures is necessary. BIGPRO trial proposes to examine the efficacy of metformin, along with diet and exercise advice, in reducing over one year the metabolic abnormalities encountered in non-diabetic subjects with central adiposity. BIGPRO is designed as a randomized double blind one-year trial of metformin (2 tabs/d, i.e. 1,700 mg/d) versus matching placebo (2 tabs/d). Men aged 40-55 years, with a waist to hip ratio greater than or equal to 0.95 and women aged 45-65 years with a waist to hip ratio greater than or equal to 0.80, are eligible to enter the trial, unless they have diabetes, cardiovascular disease, kidney dysfunction, serious illness, or are receiving extensive medical treatment. Between the two treatment groups the changes in the following endpoints will be compared after one year study: waist to hip ratio, blood pressure, blood lipids, glucose, insulin, fibrinolytic activity. At least 400 subjects are expected to complete the trial. The recruitment and follow-up will be distributed among 33 medical centers from various University Hospitals in France. If metformin proves to be effective in reducing the metabolic abnormalities associated with insulin resistance, it may be a possible candidate for a long term trial for primary prevention of cardiovascular accidents and diabetes. PMID- 1936487 TI - Insulin resistance. A unifying concept. PMID- 1936488 TI - Resistance to insulin-stimulated glucose uptake and hyperinsulinemia: role in non insulin-dependent diabetes, high blood pressure, dyslipidemia and coronary heart disease. AB - Patients with impaired glucose tolerance (IGT) and Type 2 diabetes have been shown to be more resistant to insulin-stimulated glucose uptake than individuals with normal glucose tolerance. Evidence has also been published showing that first degree relatives of patients with Type 2 diabetes are insulin resistant when compared to a matched group of relatives of subjects with normal glucose tolerance. In addition, it has recently been shown that the ability of insulin to stimulate glucose uptake varies approximately four-fold in individuals with normal glucose tolerance, and insulin resistance of a degree comparable to that seen in patients with IGT or with Type 2 diabetes is present in a significant portion of the normal population. Given a defect in insulin-stimulated glucose uptake, glucose tolerance can only be maintained if insulin resistant individuals continue to secrete greater than normal amounts of insulin. As a corollary, glucose homeostasis will decompensate when the insulin secretory response begins to fall, and the greater the decline in insulin secretion, the larger the rise in plasma glucose concentration. The net result of these changes is that plasma glucose and insulin response will be positively correlated within a population composed of glucose tolerant individuals and patients with IGT or Type 2 diabetes in the absence of significant fasting hyperglycemia. On the other hand, the relationship between plasma insulin and glucose concentration will be negatively correlated in patients with Type 2 diabetes and varying degrees of fasting hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936489 TI - Insulin-resistance, hypertriglyceridaemia and cardiovascular risk: the Paris Prospective Study. AB - The Paris Prospective Study is a long term investigation of the incidence of coronary heart disease in a large population of working men. The first follow-up examination involved 7,038 men, aged 43-54 years, and free from cardiovascular disease. A 0-2 h 75 g oral glucose tolerance test with measurement of plasma insulin and glucose levels was performed, and the major coronary heart disease risk factors were determined. Subjects with impaired glucose tolerance or diabetes at baseline (n = 943) were selected from the total population for a separate analysis of coronary heart disease mortality risk factors. After a mean follow-up of 11 years, 26 of these 943 subjects with abnormal glucose tolerance had died from coronary heart disease. In multivariate regression analysis using the Cox model, triglyceride plasma level was the only factor positively and significantly associated with death from coronary heart disease (p less than 0.006). After a mean follow-up of 15 years, 37 of the 943 had died from coronary heart disease. Significant multivariate predictors of coronary heart disease death with the Cox model were triglyceride plasma level (p less than 0.03), systolic blood pressure (p less than 0.03), and number of cigarettes per day (p less than 0.05). This epidemiological evidence of the consistency of hypertriglyceridaemia as an important predictor of CHD mortality in subjects with impaired glucose tolerance or diabetes suggests a possible role of dyslipidaemia in the excessive occurrence of atherosclerotic vascular disease in this category of subjects. It remains speculative how this dyslipidaemia can be related to arterial damage, whether by itself or as part of the insulin resistance syndrome. PMID- 1936490 TI - Hypofibrinolysis and insulin-resistance. AB - A defect in the fibrinolytic system appears to be a risk factor for the development of cardiovascular disease. Such a defect is mainly characterized by increased plasma levels of an inhibitor of fibrinolysis the plasminogen activator inhibitor 1 (PAI-1). PAI-1 levels are elevated in the common syndrome of insulin resistance as it is encountered in obese non diabetic and in non insulin dependent diabetic subjects. These levels are closely related to insulinaemia in cross sectional studies as well as in intervention studies. Although in vitro insulin stimulates the PAI-1 synthesis in hepatocyte, but not in endothelial cells, acute elevation of insulinaemia in vivo in man does not result in an increase in PAI-1 levels. The mechanisms linking insulin-resistance, insulin and PAI-1 levels in man are still not understood. PMID- 1936491 TI - Involuntary smoking and pregnancy. PMID- 1936492 TI - Human decidua: a source of cachectin-tumor necrosis factor. AB - Cachectin-tumor necrosis factor (TNF-alpha) has been implicated as a possible signal for the initiation of human parturition in the setting of infection. These studies were conducted to determine whether human decidua can produce TNF-alpha in response to bacterial lipopolysaccharide (LPS). Decidual explants from women undergoing elective cesarean sections were incubated with and without Escherichia coli LPS (25 ng/ml) for 20 h. TNF-alpha concentration in the conditioned media was measured with an enzyme-linked immunoassay and bioassay (L929 bioassay). While conditioned media from unstimulated decidual explants contained either undetectable or low levels of TNF-alpha, conditioned media from LPS stimulated decidua contained TNF-alpha (mean = 2.6 pmol/mg protein per 20 hours, SEM +/- 1.03). There was a strong correlation between the immunoreactive and bioactive TNF-alpha (Spearman rank correlation r = 0.76, P less than 0.001). We conclude that human decidua in vitro can produce TNF-alpha in response to LPS. PMID- 1936493 TI - Endometrial carcinoma; ovarian dysfunction--a risk factor in young women. AB - From a referral area comprising one-fifth of the Swedish female population we investigated possible risk factors for endometrial cancer (EC) in different age groups. Seventy-seven women aged 31-45 with EC were collected retrospectively, and 99 women aged 46-65 were consecutively collected. Both groups were compared to referents randomly selected from a population based study from the city of Goteborg. The referents consisted of 1746 women aged 39-65 years. All cases were studied by hospital record and 82% of the women aged 31-45 years and 85% of those aged 46-65 years were studied by an extensive questionnaire. Among the referents 1409 (81%) were investigated by the above-mentioned questionnaire. Hirsutism, increased body mass index (BMI) and hypertension were significantly more common in both EC groups compared to referents. Nulliparity and infertility were significantly more common in the young EC group. Referents used combined oral contraceptives significantly more often than women developing EC. There was, however, no difference between the groups with respect to the duration of medication with combined oral contraceptives. There was a significant negative correlation between cigarette smoking and the development of EC. These findings indicate that untreated ovarian dysfunction like that present in polycystic ovarian disease (PCO) with unopposed estrogen action on the endometrium is associated with EC in younger women, and that smoking may protect against EC by an 'anti-estrogenic' effect. PMID- 1936494 TI - Hormonal patterns in a successful pregnancy of a patient with late-onset 21-OH deficiency taking methylprednisolone; a case report. AB - A successful pregnancy of a young woman with late-onset congenital adrenal hyperplasia (LOCAH) is reported. Exogenous glucocorticoids are the most commonly used regimen in such cases both for suppression of adrenal overstimulation and avoiding masculinization of a female fetus. In our LOCAH patient methylprednisolone has been used for treatment. We present the management and the outcome of this pregnancy, as well as the hormonal follow-up. PMID- 1936495 TI - Early prenatal diagnosis of congenital cystic adenomatoid malformation of the lung (Stocker's type I); a case report. AB - A congenital cystic adenomatoid malformation was diagnosed by ultrasound examination at 20 week's gestation. The entire right lung was cystic and elements of poor prognosis such as hydrops fetalis and polyhydramnios were present. After verification of the karyotype, abortion was performed and autopsy confirmed prenatal findings and Stocker's type I. Cystic congenital adenomatoid malformation of the lung is a rare form of congenital pulmonary disease. Our case shows that this malformation can be accurately diagnosed during the midtrimester of pregnancy by ultrasound examination. Ultrasound examination permits an evaluation of the three types described by Stocker and may reveal certain lesions associated with poor prognosis, such as anasarca or polyhydramnios. Also, it offers the possibility to save some fetuses by surgical decompression in the immediate postnatal period, or to terminate earlier pregnancies by abortion. PMID- 1936496 TI - Outcome of triplet and quadruplet pregnancies resulting from in vitro fertilization. AB - Analysis of the outcome of 26 sets of triplet and five sets of quadruplet pregnancies resulting from in vitro fertilization (IVF) shows an high incidence of antenatal complications including first trimester bleeding (53.3 and 80%), premature onset of labour (92.3 and 67%), pregnancy-induced hypertension (28.6 and 67%) and gestational diabetes mellitus (38.5 and 33%), respectively. Intra uterine growth retardation occurred in 7.6 and 0%, while third trimester bleeding complicated 7.6 and 0% of triplet and quadruplet pregnancies, respectively. These patients were hospitalized for a mean of 22.9 +/- 19.4 and 56.0 +/- 30.5 days, respectively. The mean gestational age at delivery for triplet and quadruplet pregnancies was 31.8 +/- 2.7 and 30.3 +/- 0.6 weeks, while the mean birth weight was 1663 +/- 423 and 1232 +/- 181 g, respectively. These neonates stayed in the hospital for a mean of 28.1 +/- 16.2 and 69.6 +/- 15.5 days, respectively. The corrected perinatal mortality was 2.2% for triplets and 0% for quadruplets. These data can be used in counseling patients with triplet and quadruplet pregnancies especially those resulting from IVF. PMID- 1936497 TI - Mifepristone or vacuum aspiration in termination of early pregnancy. AB - This trial compared the termination of early pregnancy (amenorrhoea less than 43 days) by 600 mg orally of the antiprogesteron Mifepristone to the traditional method of vacuum aspiration. Fifty women were randomly assigned to either of the treatments. All the patients treated with vacuum aspiration had a complete abortion. Three of these patients developed pelvic inflammatory diseasae (PID) after the aspiration. Another patient had the uterus perforated during the procedure, and an emergency laparotomy had to be performed. The patients in the evacuation group spent more days in bed and needed longer sick leave after the treatment than the patients in the Mifepristone group. In the Mifepristone group, six patients had incomplete abortions and all were treated by evacuation. Three of the patients developed PID after the evacuation. A decrease of 40% or more in beta hCG from the initial value to the value 1 week later were invariably associated with complete abortion. In both groups the changes in hemoglobin were insignificant and no patients needed blood transfusion or emergency evacuation. The Mifepristone treatment is a simple and safe alternative to vacuum aspiration for termination of early pregnancies. PMID- 1936498 TI - Transabdominal cerclage. AB - The procedure of the transabdominal cerclage (TAC) is outlined. Sixteen cases of TAC are described in detail. The fetal salvage rate increased from 36% before to 96% after the operation. Caesarean section has to be performed at term after TAC has been applied. The transabdominal method of cerclage seems to be very promising, especially for women with severely damaged or practically absent cervices. PMID- 1936499 TI - Assessment of cervical dilatation during labor: a review. AB - Various techniques for assessment of cervical dilatation during labor or 'cervimetry' have been described, including digital, (electro)mechanical, electromagnetic and ultrasound cervimetry. In this paper the validity and usefulness of instrumental cervimetry is assessed on the basis of the available literature. Cervimetry using ultrasound transducers allows continuous and reliable recording of cervical dilatation during labor with little discomfort to the patient. In comparison with other instrumental techniques for measurement of cervical dilation ultrasound cervimetry seems to be the most promising method available. PMID- 1936500 TI - Fetal heart rate and neonatal condition related to epidural analgesia in women reaching the second stage of labour. AB - The relationship between epidural analgesia and a number of labour and delivery factors, relevant to fetal and neonatal condition, was considered in a prospective study of 200 labours reaching the second stage of labour. The group was representative of the hospital population with regard to the proportion of nulliparous women, the incidence of instrumental vaginal deliveries and the incidence of epidural analgesia (37%). The 8% of labours requiring fetal blood sampling during the first stage, and the labours with fetal heart rate (FHR) decelerations in the hour prior to second stage (25%) and during pushing (50%) were significantly more likely to have been given an epidural. Nulliparity (55%), induced labour (34%), a first stage longer than eight hours (37%), a second stage longer than 60 min (43%), maternal pushing for longer than 36 min (50%), forceps delivery (28%) and a 1 min Apgar score less than 7 (12%) were also factors associated with significantly higher rates of epidural analgesia whereas meconium (15%), a small baby (16%) and umbilical arterial metabolic acidaemia (13%) were not. FHR decelerations in labours reaching the second stage with an epidural reflect adjustments to fetal cardiovascular control and not acidaemia. PMID- 1936501 TI - Histopathological findings in placentae from patients with intra-uterine fetal death and anti-phospholipid antibodies. AB - Anti-phospholipid antibodies are associated with first trimester abortions and late intra-uterine fetal death. The histopathology of 47 placentae from 45 women with intra-uterine fetal death, including 16 patients with anti-phospholipid antibodies, was studied in order to detect potential differences between placentae from women with and without these antibodies. Thirteen patients had systemic lupus erythematosus or lupus-like disease, including 6 women with anti phospholipid antibodies. In placentae from patients with anti-phospholipid antibodies, a decrease in vasculo-syncytial membranes, fibrosis mainly in infarcted areas, hypovascular villi and thrombosis or infarction was seen significantly more often than in placentae from women without these antibodies. Of 17 placentae from 16 patients with anti-phospholipid antibodies, only 3 did not demonstrate signs of thrombosis or infarction. Thrombosis/infarction was significantly associated with a decrease in vasculo-syncytial membranes, fibrosis, hypovascular villi and an increase in syncytial knots. These findings are most likely to be the result of prolonged hypoxia due to thrombosis or infarction. It is concluded that thrombosis or infarctions are prominent features in placenta from patients with anti-phospholipid antibodies and intra-uterine fetal death. Consequently, antithrombotic treatment during pregnancy forms a rational approach in these patients. PMID- 1936502 TI - Medication during low-risk pregnancy. AB - The use of medication during low-risk pregnancy was studied prospectively in a cohort of women supervised by specialist obstetricians at a university hospital (n = 332) and a cohort of women supervised by midwives in private practice (n = 250). More women under supervision of obstetricians/gynaecologists used medication (87.7%) than women supervised by midwives (59.8%). The top-five of medication were analgesics, antacids, vitamins, antibiotics and dermatologic preparations. More research is needed to establish the risks of these medications to the offspring. PMID- 1936503 TI - Persistent pelvic pain and pelvic joint instability. AB - As accepted as the condition of pelvic pain and pelvic joint instability (PPPJI) is in pregnancy, as controversial and doubted is the same diagnosis in non pregnant women. Women suffering severe incapacitating PPPJI for years following parturition have recently founded an association. This offers a unique opportunity to investigate their characteristics. 153 of the 215 members answered a questionnaire. The majority (110) suffered PPPJI in first pregnancy with onset preceding 20 weeks gestation in 84 women. Onset was significantly earlier in users of oral contraceptives than in non-users (16.3 weeks and 20.5 weeks, respectively). The 153 women did not differ from the controls with regard to life style, diseases prior to reproduction or reproduction. Their 358 deliveries were characterized by a marked excess of post-term deliveries, a raised proportion of infants of 4000 g or more, an extremely low sex-ratio of offspring (0.84) with 54.5% female births, and a significantly raised congenital hip dysplasia rate, consistent with elevated oestrogen and relaxin levels. PMID- 1936504 TI - Is persistent pelvic pain and pelvic joint instability associated with early menarche and with oral contraceptives? AB - A study of 153 women with persistent pelvic pain and pelvic joint instability (PPPJI) following parturition, revealed that the women differed from the controls by a significantly lower age at menarche. Precocious puberty is associated with a fibrous dysplasia which resembles that seen in some PPPJI women patients at operations. Precocious puberty is known to be associated with hypothalamic dysfunction. Following cessation of lactation, 70 of 153 women did suffer galactorrhea and breast discomfort, suggesting a possible affection of the hypothalamic-pituitary system. Age at menarche was higher in users of oral contraceptives (OC) than in non-users, but onset of PPPJI was significantly earlier by gestation, and galactorrhea, and breast discomfort more frequent (60% affected as compared to 30% of non-users), suggesting that use of OC affects the hypothalamus in a manner similar to that associated with very early puberty. The widespread use of contraceptives is important if it truly leads to an increased proportion of PPPJI among reproducing women. Onset of puberty, controlled by the hypothalamus, coincides with the final step in brain development--elimination of some 40% of neuronal synapses. Age at puberty has declined by some 4 years in 100 years, and it is still falling. It cannot be excluded that in some very early maturers, redundancy of neuronal synapses persists, and that this is associated with hypothalamic dysfunction. PMID- 1936505 TI - The impact of previous danazol treatment on circulating hormone levels, follicular development and oocyte maturity in minimal-mild endometriosis. AB - The purpose of this study was to assess the impact of previous danazol treatment on peripheral endocrinology, folliculogenesis, oocyte maturity and follicular fluid endocrinology in women with minimal-mild endometriosis in a spontaneous menstrual cycle. A group of 10 women previously treated with danazol (Group A) and another group of 10 women whose endometriosis was left untreated (Group B) were studied. A group of 10 women with tubal infertility acted as a Control. Circulating hormone levels and characteristics of an endogenous luteinizing hormone (LH) surge were studied. A diagnostic laparoscopy was performed 32 h after the onset of an endogenous LH surge in all women to undertake follicular aspiration. There were no significant differences in oocyte maturity, fertilisation and cleavage rate among women studied in three study groups. The presence of peritoneal endometriosis did not affect the steroidogenic potential of the granulosa cells, and the endocrine milieu of the pre-ovulatory oocyte was comparable in all study groups. PMID- 1936506 TI - Phase II trial: an evaluation of oral saperconazole in acute vaginal candidosis: a comparison of three dosage schedules. AB - In an open, randomized phase II comparative study, 256 patients with acute vaginal candidosis (less than two episodes of vaginal candidosis in the 6 months preceding study entry) were treated with saperconazole according to one of the following treatment schedules: 2 x 100 mg o.d. for 1 day (87 patients), 2 x 100 mg b.i.d. for 1 day (83 patients), or 2 x 100 mg o.d. for 2 days (86 patients). A total of 236 patients were included in the efficacy analysis. Diagnosis of vaginal candidosis was made at the start by a direct microscopic examination of a vaginal smear and was confirmed by culture. The majority of isolated yeasts were Candida albicans (97.6%). All three dose regimens resulted in clinical cure rates of over 75%, and these were maintained for at least 1 month after the end of treatment. There was a difference in mycological cure rates between the three dose schedules (71, 85 and 92%) 1 week after the end of therapy. In view of the clinical and mycological results both 1 week and 1 month after the end of treatment, it can be concluded that a total dose of 400 mg of saperconazole given in a single day is the optimum treatment schedule. All treatment regimens were well tolerated (adverse experiences occurred in 1.6% of the patients) and the results 1 month after termination of therapy suggest a low relapse rate. PMID- 1936507 TI - Lupus anticoagulant as a marker of autoimmunity in recurrent pregnancy loss; a case report. AB - We present a patient with primary antiphospholipid syndrome, as defined by nine pregnancy losses, the presence of lupus anticoagulant (LAC), and the absence of clinical signs and symptoms of autoimmunity. A successful pregnancy was achieved by treatment with low-dose prednisone (15 mg daily) and aspirin (100 mg daily). The patient was followed-up throughout her two last pregnancies and a 6 months postpartum period. Our data indicate that LAC serves as a marker of disease in women with previous pregnancy wastages, and that aspirin-prednisone therapy is beneficial in carefully selected patients. PMID- 1936508 TI - Pasteurella multocida and female genital carcinoma; a case report to dispute the concept of genital opportunistic pathogen. PMID- 1936509 TI - Indobufen versus placebo in the prevention of restenosis after carotid endarterectomy: a double-blind pilot study. AB - A randomized clinical trial was undertaken to assess the efficacy of indobufen in inhibiting platelet adhesiveness in carotid thromboendarterectomy. The patients were treated under double-blind conditions with indobufen and with placebo, and were then assessed by means of scintigraphy with labelled platelets, ultrasonic tomography and angiography for a minimum follow-up period of 6 months. Haematological and clinical assessments were also performed. The results of the study suggest that platelet accumulation in carotid endarterectomy may be an early sign of restenosis; anti-aggregant treatment with indobufen carried out at an early stage prior to surgery inhibited platelet accumulation. The final result showed that anti-aggregant treatment had a positive influence on the short- and medium-term outcome of carotid endarterectomy. PMID- 1936510 TI - Comparative multiple-dose study of ketorolac tromethamine and diflunisal for pain following orthopaedic surgery. AB - A total of 100 patients were enrolled after orthopaedic surgery in a multiple dose, randomized, double-blind, parallel-group study to compare the analgesic efficacy and safety of 10 mg ketorolac tromethamine given orally four times daily for 3 days with 500 mg diflunisal given orally twice daily plus placebo twice daily for 3 days. Ketorolac was significantly (P = 0.04) superior to diflunisal in reducing the pain severity during the first 9 h of treatment; a difference possibly related to the more flexible dosage regimen of ketorolac. Patients and the investigator, however, rated ketorolac and diflunisal as being equally effective in terms of the overall drop in severity of pain and pain relief at the end of days 1, 2 and 3. Ketorolac-treated patients reported a total of nine adverse events and diflunisal-treated patients reported 13. It is concluded that in the treatment of acute post-operative pain a drug with a more flexible dosage regimen may provide superior pain relief. PMID- 1936511 TI - Double-blind study comparing the use of Voltaren Emulgel versus regular gel during ultrasonic sessions in the treatment of localized traumatic and rheumatic painful conditions. AB - A total of 120 patients with moderate to severe pain due to localized rheumatic or traumatic conditions participated in a double-blind, randomized trial. Patients were randomly allocated to receive ultrasonic sessions three times weekly for 4 weeks, using either diclofenac in a gel base (Voltaren Emulgel) or regular gel as a coupling medium. A statistically significant (P less than 0.01) improvement was achieved in both treatment groups in most of the evaluation criteria by the end of the first week. Treatment was prematurely discontinued due to complete cure in 60% of patients using Voltaren Emulgel compared with only 15% of those using regular gel (P less than 0.01). Physician's assessment of complete relief of pain was also statistically significant (P less than 0.01) in favour of Voltaren Emulgel throughout the trial period and the physician's overall assessment of therapeutic efficacy revealed that a satisfactory result was achieved in 86% of Voltaren Emulgel-treated patients compared with 76% of patients receiving regular gel (P less than 0.05). Tolerability was good or excellent in over 95% of patients in both treatment groups. The results of the study strongly suggest that the use of Voltaren Emulgel as a coupling medium during ultrasonic therapy is a preferable, effective alternative to the currently used regular gel. PMID- 1936512 TI - Does protease inhibitor inhibit complement activation caused by the immune complex associated with islet cell surface antibody? AB - Sera containing islet cell surface antibody were obtained from seven children with insulin-dependent diabetes mellitus soon after the onset of disease. After incubation of 51Cr-labelled rat islet cells with islet cell surface antibody, human AB-type serum with or without nafamostat mesylate was added before further incubation. Radioactivity in the supernatant was measured to determine complement dependent antibody-mediated cytotoxicity. Cytotoxicity in untreated sera [mean (+/- SD) 19.4 +/- 4.0%] was significantly (P less than 0.001) inhibited by ethyleneglycoltetraacetic acid (EGTA) (7.1 +/- 4.9%), ethylenediaminetetraacetic acid (EDTA) (2.5 +/- 0.9%) and nafamostat mesylate (2.8 +/- 1.8%). Cytotoxicity of nafamostat mesylate-treated serum was significantly (P less than 0.05) lower than that of EGTA-treated serum but not significantly different from that of EDTA treated serum. There was no difference in cytotoxicity between nafamostat mesylate-treated and untreated, inactivated human serum. The results indicate that the protease inhibitor nafamostat mesylate completely inhibited the complement activation of the immune complex associated with islet cell surface antibody by the classical and alternative pathways. PMID- 1936513 TI - Evaluation of biocompatible osteoconductive polymer activity and biocompatibility for minor oral surgery in animals and humans. AB - The speed of recovery with and biocompatibility of biocompatible osteoconductive polymer used for minor oral surgery were investigated in animals and humans. Histological and radiological follow-up of graft sites and experimental mandibular bone loss was performed in 20 rabbits. Evaluation of X-rays showed no notable difference between the treated and control animals; however, biopsies 60 days after surgery showed that those animals treated with biocompatible osteoconductive polymer did not have any interposition of connective tissue between the polymer and the new bony tissue whereas the control samples did. Radiographic follow-up of the human patients at 30 and 60 days following molar extraction showed more bone regeneration in all patients treated with the polymer compared to the controls. The results showed that the use of biocompatible osteoconductive polymer to fill secondary surgical extraction cavities provided fast prosthetic rehabilitation for the patients. PMID- 1936514 TI - Tenoxicam-induced gastropathy in the rat: a comparison with piroxicam and diclofenac sodium, and the inhibitory effects of ranitidine and sucralfate. AB - The ulcer-inducing potential, indicated by the oral dose that induced gastric ulcers in 50% of rats, was higher for tenoxicam (10.2 mg/kg) than for diclofenac sodium (34 mg/kg, equivalent to 6.8 mg/kg tenoxicam) or piroxicam (6.2 mg/kg). The mean lesion scores, a measure of the intensity of ulceration, using 16 and 32 mg/kg tenoxicam given orally were 3.6 +/- 3.4 and 8.7 +/- 7.3, respectively, compared with 9.6 +/- 6.4 and 24.7 +/- 10.5, respectively, for similar oral doses of piroxicam; the differences were statistically significant (P less than 0.05 and P less than 0.001, respectively). The mean lesion score for 32 mg/kg tenoxicam was also significantly (P less than 0.05) less than that for 160 mg/kg diclofenac sodium: 8.7 +/- 7.3 compared with 14.8 +/- 8.1. Ranitidine (20 40 mg/kg) and 260-520 mg/kg sucralfate but not 4 mg/kg ranitidine strongly inhibited ulceration induced by 32 mg/kg tenoxicam. PMID- 1936515 TI - Can a low or moderate dose of inhaled budesonide replace oral non-steroidal anti asthma treatment? AB - The efficacy of inhaled budesonide was assessed as an adjunct to and as a replacement for oral bronchodilators in an open study of 27 asthmatic patients. The patients had been treated regularly with oral bronchodilators but not with oral inhaled, or nasal steroids during the 2 3 months prior to the study. The study consisted of four treatment periods: 1, oral bronchodilator plus inhaled placebo for 1 week; 2, oral bronchodilator plus 400 micrograms inhaled budesonide twice daily for 3 weeks; 3,400 micrograms inhaled budesonide twice daily for 3 weeks; 4,200 micrograms inhaled budesonide twice daily for 3 weeks. Lung function measurements increased when budesonide was included with oral bronchodilators and there was a corresponding decrease in symptoms and rescue inhaler usage. Removal of oral bronchodilators from therapy did not significantly alter lung function and symptoms, whereas decreasing the dose of budesonide produced a slight reduction in peak expiratory flow and an increase in inhaled bronchodilator consumption. PMID- 1936516 TI - The thyroid hormone secretory pathway--current dogmas and alternative hypotheses. PMID- 1936517 TI - Corticosteroids, kidneys, sweet roots and dirty drugs. PMID- 1936518 TI - Medicinal uses of licorice through the millennia: the good and plenty of it. PMID- 1936519 TI - Overexpression of an immunologically-intact, secreted form of human thyroid peroxidase in eukaryotic cells. AB - Recombinant human thyroid peroxidase (hTPO) has been expressed in eukaryotic cells as both the membrane-associated enzyme and as a secreted protein. We now report overexpression of the secreted form of recombinant hTPO in eukaryotic cells. For hTPO gene amplification we used a vector containing the mouse dihydrofolate reductase (DHFR) gene. Stably transfected Chinese hamster ovary (CHO) cells were grown in the presence of increasing concentrations of methotrexate (MTX) and hTPO expression was measured immunologically in an enzyme linked immunosorbent assay (ELISA). Progressive overexpression of secreted hTPO occurred up to a final MTX concentration of 10,000 nM. Slot-blot analysis of genomic DNA from CHO cells expressing truncated hTPO revealed amplification profiles of the DHFR and hTPO genes to be similar, in parallel with hTPO protein production. High-level expression of secreted hTPO offers the potential for obtaining large amounts of biologically and immunologically active protein for future study. PMID- 1936520 TI - Identification of multiple transcription start sites in the human insulin-like growth factor-I gene. AB - We have localized four transcription initiation sites in the human insulin-like growth factor-I (IGF-I) gene. Two transcription start sites were identified which result in a longer and shorter version of the leader derived from the known exon 1 of the IGF-I gene. Transcription starting at the upstream transcription initiation site results in a leader exon 1 of about 1155 nucleotides (nt), whereas transcription starting at the downstream initiation site results in a leader of about 240 nt. The majority of the transcripts initiate at the latter site. We further identified a region in the human IGF-I gene between exons 1 and 2, which shows a high degree of homology with the rat IGF-I leader exon 1B. By means of the polymerase chain reaction (PCR) we detected human IGF-I mRNAs containing this novel leader. The corresponding exon was designated exon 1B according to the rat IGF-I gene terminology. PCR and RNase protection analyses identified two transcription start sites within this alternative leader exon 1B. Transcription initiated at the most upstream start site results in a leader of about 750 nt, whereas transcription starting at the downstream site is heterogeneous, resulting in leaders of 65-75 nt long. No consensus TATA-box or AT rich regions are present immediately upstream of all four transcription start sites identified, nor are these regions particularly GC-rich. The IGF-I gene is known to be expressed differentially in a tissue- and development-specific fashion. Differential activation of multiple promoters could very well play a crucial role in IGF-I gene regulation. PMID- 1936521 TI - Transfection of avian vitamin D-dependent calbindin-D28K 5' flanking promoter sequence in primary chick kidney cells. AB - Expression of the vitamin D induced calbindin-D28K protein is transcriptionally controlled by the steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in a tissue-specific manner in the intestine and kidney. In order to examine the cis acting elements of the calbindin-D28K promoter and its modulation by 1,25 dihydroxyvitamin D3, chimeric plasmids containing 2.1 kb of 5' flanking region linked to the reporter gene chloramphenicol acetyl transferase (CAT) were transfected by lipofection into primary cultures of chick kidney cells. Transfected chick kidney cells exhibited a high basal expression of the chloramphenicol acetyl transferase gene, reflecting the strong activity of the calbindin-D28K promoter. Expression of the pCaBP2.1 reporter gene was increased 2 fold in the presence of the hormone 1,25(OH)2D3 in the primary kidney cells. Deletion of a 1.42 kb fragment ending -679 base pairs upstream from the transcription start site led to a 2-fold repression in the reporter gene activity by the hormone 1,25(OH)2D3 in primary chick kidney cultures. These preliminary results suggest that both positive and negative elements normally act to regulate the expression of the calbindin-D28K gene in primary chick kidney cells. PMID- 1936522 TI - Oxytocin stimulates progesterone production by bovine granulosa cells isolated before, but not after, the luteinizing hormone surge. AB - Oxytocin and its mRNA have been detected in bovine granulosa cells, but the function of follicular oxytocin is not well understood. We have shown previously that oxytocin exerts a specific, dose-dependent, stimulatory effect on progesterone secretion by granulosa, but not theca cells isolated from bovine preovulatory follicles obtained 48 h after the initiation of luteolysis. The objective of the present study was to characterize the development of granulosa cell responsiveness to oxytocin during the follicular phase. Granulosa cells and theca interna were isolated form preovulatory follicles early in the follicular phase (24 h after the initiation of luteolysis) or after the luteinizing hormone (LH) surge and cultured in defined medium for 5 days with or without oxytocin and in the presence or absence of gonadotropins. Granulosa, but not theca cells obtained before the LH surge increased progesterone production 3.3-fold in response to oxytocin. However, late in the follicular phase, after the LH surge, granulosa cells did not respond to oxytocin (or to follicle-stimulating hormone (FSH) or LH). These findings suggest that the LH surge (1) stimulates granulosa cells to maximal progesterone secretion, so that they cannot be further stimulated, (2) abolishes the responsiveness of granulosa cells to oxytocin, or (3) stimulates granulosa cells to increase oxytocin production, so that exogenous oxytocin has no additional effect. PMID- 1936523 TI - Estrogen synthetase (aromatase). The cytochrome P-450 component of the human placental enzyme is a glycoprotein. AB - Estrogen synthetase (aromatase) is a cytochrome P-450 enzyme system which converts androgens to estrogens. Although this enzyme has been purified and the cDNA-derived amino acid sequence elucidated, very little is known regarding post translational modifications of this physiologically crucial enzyme. We show here that the cytochrome P-450 component, P-450ES, purified from human term placental microsomes, is a glycoprotein based on the following evidence: its molecular weight is decreased following treatment with endoglycosidase F, concanavalin A biotin specifically binds to this protein immobilized on nitrocellulose, and its oligosaccharide composition is consistent with a single N-linked fucosylated complex type carbohydrate chain. In a reconstitution system, the aromatase activity using the endoglycosidase F-treated P-450ES was reduced by about 35-40% relative to the native form, regardless of whether androstenedione or testosterone was used as substrate. PMID- 1936524 TI - A recombinant-DNA-derived modification of human growth hormone (hGH44-191) with enhanced diabetogenic activity. AB - A modified human growth hormone (hGH) that lacks the first 43 residues of the intact hormone was prepared by recombinant-DNA technology. For preparative purposes an additional alanine was made the amino terminal residue. Sequence analysis and tryptic peptide mapping combined with amino acid analyses confirmed the structure of the polypeptide. Less than 2% N-terminal methionine was detected. The hGH44-191 was estimated to be at least 10 times more active than hGH in producing glucose intolerance in obese yellow mice (Avy/A) and was equipotent to hGH in increasing serum free fatty acids in fasted, hypophysectomized rats. The peptide did not promote growth in hypophysectomized rats nor did it exhibit early (1h) insulin-like activity in fasted, hypophysectomized rats, as indicated by its failure to lower blood glucose and fatty acids. The modified hGH was inactive in the Nb-2 cell assay but was about one-third as active as hGH in stimulating the pigeon crop sac. In radioimmunoassays using 125I-labeled hGH and polyclonal antibodies to intact hGH, cross-reactivity of hGH44-191 was less than 1%. We conclude that removal of the amino terminal portion of hGH enhances its diabetogenic properties, and that this activity does not depend upon the ability to promote growth. Furthermore, the insulin-like activity can be separated from its diabetogenic action by deletion of the first 43 amino terminal residues. This is the first report of a modified hGH that has anti-insulin effects greater than hGH itself. PMID- 1936525 TI - Insulin activation of rat prolactin promoter activity. AB - The role of insulin regulation of rat prolactin (rPRL) gene transcription was studied using GH4 rat pituitary tumor cells transiently transfected with plasmids containing proximal rPRL promoter fragments ligated to the reporter gene luciferase. Here we show that insulin, at nanomolar concentrations, has a rapid effect on the rPRL promoter stimulating its activity about 1.8-fold within 4h after hormone addition. Furthermore, we have mapped the rPRL promoter element responsible for mediating insulin hormone action between positions -212 and +73. The stimulation of rPRL gene transcription by insulin was abolished when insulin doses extended into the micromolar range. Thus, rPRL promoter sequences downstream of -212 are sufficient to mediate increased rPRL gene transcription in response to insulin. PMID- 1936526 TI - Redistribution of cathepsin B activity from the endosomal-lysosomal pathway in chick intestine within 3 min of calcium absorption. AB - Earlier work has suggested that calcium-containing lysosomes are involved in 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)-stimulated intestinal absorption of the divalent cation. In the present report immunofluorescent labelling studies on fixed frozen sections of chick intestine were undertaken to determine whether lysosomes could respond to calcium transport conditions in less than 5 min. Tissue prepared from vitamin D-deficient chicks dosed with vehicle or 1.3 nmol of 1,25(OH)2D3 15 h prior to use was immunofluorescently labelled for cathepsin B, a lysosomal protease. In the absence of calcium absorption, punctate staining was found in the region below the terminal web, and more diffusely in the cytoplasm. The intensity of staining was noticeably greater in sections from 1,25(OH)2D3 treated than control chicks. In sections prepared after 3 min of calcium absorption, cathepsin B staining was localized near the basal and lateral membranes of the epithelial cells. After 30 min of transport, the protease was found in the villus core regardless of vitamin D status; however, immunoreactivity within the epithelial cells of 1,25(OH)2D3-treated chick intestine had returned to pretransport intensity, whereas that of controls had not. To further investigate the specificity of the cathepsin B antibody, the intracellular compartmentalization of the protease was determined by biochemical methods. Using dosing procedures and calcium transport times equivalent to those for the immunofluorescent studies mucosae were collected by scraping, homogenized, and subcellular fractions prepared by a combination of differential and Percoll gradient centrifugation. In the absence of calcium transport, cathepsin B-specific activity was enhanced in whole homogenates, endocytic vesicles, and a lysosomal fraction prepared from intestinal epithelium of 1,25(OH)2D3-treated chicks, relative to vitamin D-deficient controls. After 3 min of calcium absorption, a profound (approximately 4-fold) decrease in endocytic vesicle cathepsin B activity was found regardless of vitamin D status, as well as a similar marked decrease in lysosomes prepared from vitamin D-deficient, but not -treated, chicks. After 30 min of calcium transport, endocytic vesicles prepared from either vitamin D-deficient or 1,25(OH)2D3-treated birds had recovered cathepsin B activity to pretransport levels. However, lysosomes prepared from rachitic chicks remained low in protease levels relative to equivalent fractions from dosed chicks. Thus, biochemical analysis of cathepsin B activity in putative endocytic vesicles and lysosomes supports the intracellular redistribution of protease visualized with immunofluorescence microscopy. PMID- 1936527 TI - Effect of calcium on membrane potential behavior in a rat pituitary cell line (GH3). AB - The effects of intracellular calcium buffering and increasing bath Ca2+ on spontaneous membrane depolarizations expressed by the clonal rat pituitary cell line GH3 were examined by use of the whole-cell patch-clamp technique. Increasing intracellular calcium buffering capacity caused the duration of spontaneous depolarizations to increase without altering other parameters of membrane potential activity. Increasing bath Ca2+ caused a decrease in duration. These results suggest that the duration of spontaneous membrane depolarization in GH3 cells is regulated by the accumulation of free intracellular Ca2+. The behavior of spontaneous depolarizations measured with the perforated-patch variation of whole-cell patch-clamp techniques closely resembled that obtained in standard whole-cell patch-clamp measurements with an intracellular calcium buffer of 200 microM EGTA with free Ca2+ adjusted to 100 nM. PMID- 1936528 TI - Developmental and tissue-specific regulation of ovine insulin-like growth factor II (IGF-II) mRNA expression. AB - Insulin-like growth factor II (IGF-II) is believed to be involved in the development of the fetus. Northern and dot-blot analysis of RNA isolated from different sheep tissues at various stages of development were undertaken, revealing that the ovine IGF-II gene is expressed as a multitranscript family (6.0, 5.1, 5.0, 4.7, 3.8, 2.9, 2.3, 1.9, 1.6, 1.3 kb). Evidence that the ovine IGF-II gene may be regulated in a developmental, tissue-specific, co-ordinate or independent manner is presented. The developmental profile of IGF-II gene expression correlates with plasma levels (Mesiano et al. (1989) Endocrinology 124, 1485-1491), and suggests that the rapid fall in plasma concentration at term can be attributed to regulation at the transcriptional level. With the exception of the kidney, IGF-II expression was down-regulated at birth in all tissues examined. As in man but not rat, an adult liver-specific transcript was detected and attributed to different 5' untranslated regions in the fetal and adult IGF-II mRNAs. The finding of IGF-II transcripts in all tissues examined supports evidence from other species of autocrine/paracrine roles for IGF-II in the development of the fetus. PMID- 1936529 TI - The human relaxins: consensus and dissent. PMID- 1936530 TI - Placental prolactin-like proteins in rodents: variations on a structural theme. PMID- 1936531 TI - Is a sorting signal necessary to package proteins into secretory granules? PMID- 1936532 TI - Melatonin: the chemical expression of darkness. PMID- 1936533 TI - Is tamoxifen also an anti-lactogen? PMID- 1936534 TI - Progesterone effect on intracellular inorganic sulphate in uterine epithelial cells. AB - The effect of progesterone on the available intracellular sulphate pool in subcultured glandular epithelial cells from guinea-pig endometrium is reported. Progesterone in concert with 17 beta-estradiol was shown to cause an increase in the available intracellular sulphate pool. The maximum effect was obtained for 10(-8) M and 10(-7) M progesterone. This effect of progesterone on the available intracellular sulphate pool essentially concerned the intracellular inorganic sulphate and was inhibited by the antiprogesterone steroid RU 486 (5 x 10(-7) M). Sulphate incorporation into the endometrial epithelial cells was suppressed by the inhibitor of anion transport diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and the protein synthesis inhibitor, cycloheximide. These results would suggest that a sulphate transport system may be involved in the accumulation of the intracellular sulphate, stimulated by progesterone. This phenomenon could be an early process in the preparation of the endometrium for implantation. PMID- 1936535 TI - Local control of Leydig cell arginine vasopressin receptor by naloxone. AB - Arginine vasopressin (AVP) and beta-endorphin are present within the testis where they could act as paracrine effectors of steroidogenesis. In this study we investigated the effect of naloxone, an opioid receptor antagonist on Leydig cell AVP receptor. Intratesticular injection of increasing doses of naloxone (0.1-100 micrograms) resulted 24 h later in a dose-dependent increase in Leydig cell AVP binding capacity. This effect occurred locally since s.c. injection of similar doses of naloxone did not alter the testicular AVP receptor content and intratesticular injection enhanced AVP receptor density only in the naloxone treated testis but not in the contralateral vehicle-treated testis. Scatchard plot analysis of the data revealed that naloxone locally injected altered AVP binding capacity without change in affinity. These results suggest that in addition to their known paracrine effects in the testis, endogenous opioid peptides may locally control the testicular AVP system by modulating AVP receptor capacity. PMID- 1936536 TI - Partial characterization of a unique mitogenic activity secreted by rat Sertoli cells. AB - Sertoli cell conditioned medium (SCCM) contains a potent mitogen, Sertoli cell secreted growth factor (SCSGF). A431 cells, derived from a human epidermoid carcinoma have provided an excellent model cell line for the study of this apparently unique activity secreted by rat Sertoli cells in vitro. Previously, it was shown that SCCM contained an epidermal growth factor (EGF)-like activity which was thought to be the mitogen for A431 cells. The present study showed that these two factors are distinct entities. The secretion of the EGF-like activity decreased with increasing number of culture days, while that of SCSGF and of another Sertoli cell specific protein, transferrin remained constant. The addition of SCCM stimulated whereas 2.5 ng/ml EGF inhibited the A431 cell growth. The proliferative response of A431 cells to a wide variety of growth factors and known Sertoli cell secretions was investigated. SCSGF was the only growth factor of known Sertoli cell secretions tested (transforming growth factors (TGF alpha, TGF beta), EGF, bombesin, fibroblast growth factor (FGF), platelet derived growth factor (PDGF), insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), prostaglandins E-1 and E-2, insulin, transferrin and lactate) which stimulated A431 cell proliferation. SCSGF was mitogenic for A431 cells even in the presence of serum in the culture medium. The partially purified SCSGF was heat- and acid stable, protease-sensitive with a molecular weight of 14,000. It did not bind to heparin or concanavalin A-Sepharose. The secretion of a mitogenic activity by the Sertoli cell which is different from other previously identified growth factors and which coincides with active spermatogenesis could have important implications in the regulation of spermatogenesis. PMID- 1936537 TI - Expression of porcine pro-opiomelanocortin in mouse neuroblastoma (Neuro2A) cells: targeting of the foreign neuropeptide to dense-core vesicles. AB - Pro-opiomelanocortin (POMC) is the precursor to several pituitary hormones and neuropeptides including adrenocorticotropic hormone (ACTH) and beta-endorphin (beta-END). In neuroendocrine cells, peptide hormones and neuropeptides are targeted to the dense-core vesicles of the regulated secretory pathway. These vesicles are transported to the ends of cellular extensions where they are stored until they release their content upon external stimulation of the cell. In order to study the cellular mechanisms involved in targeting of neuropeptides, we have expressed POMC in Neuro2A cells, a cell line of neural origin. Using immunofluorescence labeling and immunoelectron microscopy we show that in Neuro2A cells POMC is packaged in dense-core vesicles which accumulate at the tips of cellular processes. Intracellular accumulation of POMC was not observed in NIH 3T3 fibroblasts. When a soluble form of an integral membrane protein, neutral endopeptidase (E.C. 3.4.24.11) (secNEP), was expressed in Neuro2A cells, the protein was found to be constitutively secreted without prior accumulation in dense-core vesicles. Our results suggest that in Neuro2A cells, targeting to the regulated secretory pathway is restricted to peptide hormones and neuropeptides and establish this cell line as a valid model for studying the molecular events involved in neuropeptide sorting into the regulated secretory pathway. PMID- 1936538 TI - Studies on the regulation and characterization of plasma stanniocalcin in rainbow trout. AB - Stanniocalcin (STC) is a hormone that is synthesized and secreted by the corpuscles of stannius (CS), endocrine glands that are unique to the bony fishes. The hormone inhibits Ca2+ transport from the aquatic environment into the bloodstream by way of the gills. Previous in vitro studies by our laboratory have shown that STC secretion is positively regulated by Ca2+ in a time- and dose dependent fashion. In this report, we have examined circulating levels of STC in free-swimming, cannulated rainbow trout and how hormone levels are affected by surgical stress and intra-arterial infusions of mono and divalent cations. In addition, the plasma hormone has been concentrated by immunoaffinity chromatography and characterized by Western blot analysis. The results suggest that the in vivo response of the CS is extremely rapid and Ca(2+)-specific and that STC circulates in multiple molecular weight forms. PMID- 1936539 TI - Growth hormone-releasing factor does not activate protein kinase C in somatotrophs. AB - The purpose of this study was to investigate the involvement of protein kinase C in growth hormone-releasing factor (GRF) action by directly measuring the effect of GRF on protein kinase C activity in purified male rat somatotrophs. Somatotrophs were incubated with GRF (10(-7) M) for 0.33, 1, 3, 10, 30 and 90 min. Protein kinase C present in soluble and particulate fractions was partially purified using DEAE-cellulose chromatography, and protein kinase C activity was assayed. In control experiments, to insure protein kinase C activity could be activated, two known protein kinase C activators, phorbol 12-myristate 13-acetate (PMA) and dioctanoyl-rac-glycerol (diC8) were added for 3 min. Protein kinase C activity is present in somatotrophs. Under basal conditions the majority of the enzyme activity is located in the cytosol (approximately 90%). The protein kinase C activators caused a significant translocation of protein kinase C activity from soluble to particulate fractions at 3 min. GRF did not cause a translocation of protein kinase C activity even though GH release was significantly increased by 3 min. GRF did not significantly alter the specific activity of protein kinase C in the soluble or particulate fractions, except for a small (approximately 10%) increase in soluble activity at 90 min. We conclude that protein kinase C is present in the somatotrophs of the anterior pituitary. Protein kinase C, however, does not mediate the action of GRF and its role in signal transduction in somatotrophs awaits elucidation. PMID- 1936540 TI - Calcium fluxes in rat thyroid FRTL-5 cells. Evidence for Ca2+ entry after stimulation with ATP. AB - The relationship between ATP-induced uptake of 45Ca2+ and the ATP-induced changes in [Ca2+]i was investigated in rat FRTL-5 thyroid cells. Addition of 1 microCi 45Ca2+/ml together with ATP induced a time- and dose-dependent increase in uptake of 45Ca2+, the uptake being still significantly above control after 30 min. Resting intracellular free Ca2+ levels ([Ca2+]i), measured using Fura-2, was determined to be 60 +/- 14.3 nM (mean +/- SE). ATP induced a rapid, transient increase in [Ca2+]i (785 +/- 56.2 nM) followed by a plateau phase (127 +/- 34.3 nM). In a Ca(2+)-free buffer, the ATP-induced transient was significantly decreased (357 +/- 57.4 nM, p less than 0.05), and the plateau phase was abolished. The results suggested that stimulating FRTL-5 cells with ATP induced an influx of Ca2+, possibly by a mechanism dependent on a transient increase in [Ca2+]i. To further test this possibility, the intracellular Ca2+ chelator 1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) was tested. In cells loaded with BAPTA, the ATP-induced uptake of 45Ca2+ was greatly enhanced, while the ATP-induced transient increase in [Ca2+]i was almost totally abolished. In cells stimulated with ATP in a Ca(2+)-free buffer, readdition of Ca2+ after termination of the ATP response induced a rapid increase in [Ca2+]i. Furthermore, addition of Mn2+ to cells stimulated with ATP induced a more rapid quenching of Fura-2, compared to that seen in control cells. The results indicate that stimulating FRTL-5 cells with ATP induces a rapid release of Ca2+ from intracellular stores, followed immediately by an increase in plasma membrane conductance and influx of extracellular Ca2+. The ATP-induced change in [Ca2+]i may function as a signal enhancing influx of extracellular Ca2+, although some other unknown mechanism(s) is also needed. PMID- 1936541 TI - Phorbol ester and vasopressin activate phospholipase D in Leydig cells. AB - In the present study evidence is provided for the existence of phospholipase D (PLD) activity in rat Leydig cells. Leydig cells were cultured and labelled with [3H]myristic acid. In the presence of ethanol, phorbol 12-myristate 13-acetate (PMA) stimulated the formation of [3H]phosphatidylethanol ([3H]PEt) in a dose dependent manner at the expense of [3H]phosphatidic acid ([3H]PA). In cells prelabelled with [3H]choline, PMA caused a rapid increase in intracellular free [3H]choline. The time course of [3H]PEt formation was similar to the time course of intracellular [3H]choline formation. The data taken together support the notion that PMA stimulates phosphatidylcholine (PC) hydrolysis by a mechanism, which principally involves PLD. Activation of PLD by PMA was inhibited by long term pretreatment of cells with PMA to downregulate protein kinase C (PKC) and by pretreatment with staurosporine. These data support the notion that activation of PLD by PMA is dependent on PKC. Arginine vasopressin (AVP) caused a rapid stimulation of PLD activity in the cells. This activation was inhibited after down-regulation of PKC, indicating that the agonist acts by a mechanism similar to that of PMA. PMID- 1936542 TI - Thyrotropin-releasing hormone-induced cytosolic calcium transients: characterisation of store refilling in bovine anterior pituitary cells. AB - The intracellular calcium ion concentration ([Ca2+]i) in individual bovine anterior pituitary cells was measured using fura-2 and ratiometric imaging. Addition of thyrotropin-releasing hormone (TRH) in the presence of external calcium ion ([Ca2+]e; 1 mM) caused a rapid transient increase in [Ca2+]i falling to a plateau which remained above pre-stimulation levels in the continued presence of TRH. Decreasing [Ca2+]e to 0.1 microM decreased [Ca2+]i. At 0.1 microM [Ca2+]e, the first TRH addition caused the rapid transient rise in [Ca2+]i but no plateau phase and a second addition of TRH did not cause a second transient rise. However, the second application of TRH in 0.1 microM [Ca2+]e caused a rise in [Ca2+]i if it was preceded by transient exposure of the cells to 2 mM [Ca2+]e. The presence of nitrendipine, 2,5-di-(tert-butyl)-1,4 benzohydroquinone (tBHQ), or TRH during the re-exposure to external calcium blocked this recovery of subsequent responses to TRH in the presence of only 0.1 microM [Ca2+]e. We conclude that refilling of the calcium stores depleted by TRH occurred only after the removal of agonist, used a tBHQ-sensitive uptake mechanism, and was mainly sustained by voltage-gated calcium entry into the cells. PMID- 1936543 TI - Absence of lutropin (LH) receptor mRNA in the rat thyroid: further evidence for specificity cross-over at the thyroid-stimulating hormone receptor level. AB - Chorionic gonadotropin (CG) and purified lutropin (LH) activate intact thyroid tissue and isolated thyroid cells. A recent report has suggested that the presence of aberrant LH/CG receptors in human and rat thyroid tissue may interact with gonadotropin thus explaining the mechanisms of thyroid cell stimulation. To detect putative thyroidal LH receptor mRNA, a segment of the transmembrane region containing domains 3 through 6 of the rat (r) LH receptor was targeted for amplification using the polymerase chain reaction (PCR). cDNA prepared from a rLH receptor-positive control tissue (testis) was efficiently amplified under stringent annealing conditions giving a 486 bp product as predicted. However, cDNAs from thyroidal tissue and from the thyroid-stimulating hormone (TSH)- and hCG-responsive 1B-6 subclone of Fisher rat thyroid cells (FRTL-5) yielded no detectable 486 bp product. A smaller (non-LH) fragment amplified to similar extents from both testis and thyroidal cDNAs provided a useful internal control for amplification. This allowed the conclusion that specificity cross-over between LH/CG and TSH occurs at the TSH receptor and that the LH/CG receptor gene is transcriptionally silent in rat thyroidal cells. PMID- 1936544 TI - Differential modulation of thymosin genes in the immature rat ovary by gonadotropins. AB - A cloned thymosin beta-10 cDNA and a synthetic oligonucleotide specific for the thymosin beta-4 gene were used to study the in vivo expression of these two genes in the immature rat ovary in response to exogenously administered gonadotropins. Despite the fact that both genes were co-expressed in the rat ovary, it became evident that they exhibit distinctly unique differential responses to in vivo hormonal challenge. Administration of pregnant mare's serum gonadotropin (PMSG) to immature rats provoked a pronounced stimulation of ovarian thymosin beta-10 expression, the maximal effect (2- to 4-fold) of which coincided with the time at which folliculogenesis was also maximally enhanced. In contrast, the transcriptional status of the thymosin beta-4 gene varied little in response to the PMSG. Administration of human chorionic gonadotropin (hCG) to PMSG-primed rats inhibited ovarian thymosin beta-10 but stimulated thymosin beta-4 gene expression. These findings suggest that despite a mutually high degree of homology, these two proteins may, under the influence of gonadotropins, play independent roles in normal ovarian function. PMID- 1936545 TI - Effects of 1,25-dihydroxycholecalciferol and calcium on calcitonin mRNA levels in suckling rats. AB - The chronic administration of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) to 9 day-old suckling rats induced no change on day 13 in the calcitonin (CT) mRNA steady-state level of thyroid glands measured by Northern hybridization. Thyroidal CT contents were decreased in relation to increased plasma calcium levels in animals treated with 0.1 or 1 microgram 1,25-(OH)2D3/kg. Using a lower dose (0.01 microgram/kg), neither plasma calcium, nor thyroidal CT contents were changed. No correlation was found between CT mRNA levels and thyroidal CT contents as well as for plasma CT levels and thyroidal CT contents since hormone in blood remained unchanged after treatment by the active vitamin D3 metabolite. Intraperitoneal calcium administration in fasted 13-day-old rats was associated with a 5-fold increase in plasma CT 30 min after injection, but CT mRNA levels were unchanged within 240 min. By contrast, stomach gavage with calcium in fasted 13-day-old rats induced a sustained increase in plasma CT (X2), and a 4-fold increase in the steady-state level of CT mRNA. Calcium per se is a potent stimulator of CT release in suckling rats, but did not change the amount of CT mRNA. However, gastrointestinal factors may be implied directly or indirectly in the increased CT mRNA level after calcium gavage. In conclusion, 1,25-(OH)2D3 which is known to affect CT gene expression in adult rats is ineffective in 13 day-old suckling rats. This observation may be related to developmental changes in the amount of 1,25-(OH)2D3 receptors of C cells. PMID- 1936546 TI - Comparison of peptidyl-glycine alpha-amidation activity in medullary thyroid carcinoma cells, pheochromocytomas, and serum. AB - With an assay based on the radioimmunological detection of the formation of the C terminal amide function on a neuropeptide Y-like substrate, amidation enzyme activity with apparent Mr of 56,000 and 38,000 was found in pheochromocytoma extracts. The larger molecular form of amidating enzyme was also expressed and secreted from medullary thyroid carcinoma cells in a dexamethasone-suppressible way. Serum contained high levels of amidating enzyme activity with no difference between normal subjects and patients with pheochromocytomas. However, the majority of the amidating activity in serum was of much larger size, Mr between 80 and 105,000, compared to that released from the endocrine cells. No major difference was found between the molecular forms of amidation enzyme from tissues and from serum either in respect of enzyme kinetics or in respect of requirements for the cofactors copper and ascorbate. The major serum forms of enzyme were relatively independent of exogenous copper; however, they could still be quenched by cobber chelating agents. It is concluded that the molecular weight forms of the amidating enzyme circulating in serum are much larger than the soluble enzyme stored and secreted from most endocrine tissues. PMID- 1936547 TI - G protein modulation by estrogens. AB - Levels of various G protein subunits were assayed by immunoblot and densitometry, using specific antibodies, in anterior pituitaries and striata of female rats exposed to physiological or pharmacological modifications of ovarian hormone levels and, for comparison, in the same tissues of coeval male rats. Treatment of ovariectomized rats with 17 beta-estradiol 10 micrograms/rat/day for 5, 10 or 20 days induced a time-dependent rise in plasma prolactin (PRL) levels. While no change in G protein levels was observed in the striatum, estrogen treatment induced a significant reduction of all pituitary G protein levels except those of alpha i1, which remained unchanged, and of alpha s42, which increased in a time dependent manner. A highly significant correlation was observed between pituitary alpha s42 values and plasma PRL levels. During the estrous cycle, pituitary values of alpha o, alpha i3 and alpha s47 were generally lower than those of ovariectomized rats, suggesting the existence of tonic inhibitory influence of circulating ovarian hormones. Pituitary levels of alpha o, alpha i1 and alpha s42 also showed a significant modulation during the various phases of the estrous cycle, and those of alpha o, alpha i3, alpha s47 and beta were significantly lower in female than in male rats. No significant effects of estrous cycle hormone variations or sex differences were observed in the values of striatum G proteins. In conclusion, these data clearly indicate that ovarian hormones, and particularly estrogens, have a significant and specific effect on pituitary G protein levels which may modulate the secretion of pituitary hormones such as PRL. PMID- 1936548 TI - Lack of involvement of arachidonic acid metabolism in chicken gonadotropin releasing hormone II (cGnRH-II) stimulation of gonadotropin secretion in dispersed pituitary cells of goldfish, Carassius auratus. Identification of a major difference in salmon GnRH and chicken GnRH-II mechanisms of action. AB - Gonadotropin (GTH) release in static incubations of dispersed goldfish pituitary cells was stimulated by chicken GTH-releasing hormone II (cGnRH-II), salmon (s)GnRH, phospholipase A2, phospholipase C, phospholipase D, and arachidonic acid (AA). Coincubations with nordihydroguaiaretic acid (NDGA), 5,8,11,14 eicosatetraenoic acid, and indomethacin did not alter the GTH responses to cGnRH II. In contrast, NDGA reduced sGnRH-stimulated GTH release. Incubation with Ca(2+)-deficient medium abolished the GTH responses to cGnRH-II, reduced sGnRH stimulated GTH release, but did not alter AA actions on GTH secretion. Apomorphine, a dopamine agonists that had been shown to partially inhibit the GTH responses to sGnRH and to abolish those induced by cGnRH-II, did not affect the hormone response to AA. However, the partial inhibitory actions of NDGA and apomorphine on sGnRH-induced GTH release were additive. These findings suggest the existence of a major difference in cGnRH-II and sGnRH stimulation of GTH release--AA metabolism is not involved in cGnRH-II, as opposed to sGnRH actions. This difference in second messenger activation may also explain the differential sensitivity of the two GnRH peptides to dopamine inhibition and manipulations of extracellular Ca2+ availability. The results further suggest that dopamine and AA affect GTH release via non-overlapping signal transduction pathways. PMID- 1936549 TI - Synthesis and examination of antigenicity of four hormonogenic sites and two non hormonogenic sites of human thyroglobulin. AB - Four peptides (HTg-1, 1-10; HTg-2, 2547-2558; HTg-4, 2592-2603; HTg-6, 2737-2748) which contain hormonogenic acceptor tyrosine (Tyr) residues and two control peptides (HTg-3, 2582-2591; HTg-5, 2687-2694) of human thyroglobulin (Tg) were synthesized, radioiodinated and their binding with serial anti-human Tg antisera which had been raised in two rabbits (TG-1, TG-2) tested. Although increased binding of each of the six peptides was observed, HTg-4 and HTg-2 had higher binding whereas HTg-1 and HTg-6 showed lower binding with the immune gamma globulin from both rabbits. Each of the six peptides was iodinated with inorganic iodine (127I) using the chloramine-T method and the inhibitory activity of each peptide on the interaction between 125I-T4 and anti-Tg antibodies was tested. At the same time, Tg obtained from a normal thyroid tissue (NTg, iodine content 0.38%) and from a Hurthle cell adenoma (CTg, iodine content 0.000%) were also tested for inhibition of 125I-T4 binding. 125I-T4 binding with rabbit anti-Tg antisera was displaced not only by NTg and CTg but also by three out of four hormonogenic peptides. Among the three peptides, HTg-2 had the highest inhibitory activity, inhibiting 125I-T4 binding to the extent of 21.5% (TG-1) and 16.0% (TG 2). Two control peptides (HTg-3, HTg-5) did not inhibit 125I-T4 binding with anti Tg antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936550 TI - Interactions between activin and follicle-stimulating hormone-suppressing protein and their mechanisms of action on cultured rat granulosa cells. AB - Direct roles of follicle-stimulating hormone (FSH)-suppressing protein (FSP) and activin in regulation of ovarian granulosa cell differentiation have been reported recently. The present study further investigated the effects of these peptides on steroidogenesis and inhibin production as well as cAMP generation in cultured granulosa cells from immature, diethylstilbestrol (DES)-treated rats. In the presence of FSH (20 ng/ml) and activin (30 ng/ml), which enhanced FSH-induced aromatase activity, progesterone production and inhibin production, FSP (1-100 ng/ml) reversed the stimulating activities of activin in a dose-dependent manner. In addition, activin reversed the inhibitory effects of FSP on FSH-induced aromatase activity and inhibin production. In the presence of FSH, activin enhanced FSH-stimulated extracellular cAMP accumulation, and FSP caused a reduction in extracellular cAMP. Activin but not FSP also stimulated basal cAMP level. In the presence of forskolin, a potent stimulant of adenyl cyclase activity which stimulated extracellular cAMP, aromatase activity, progesterone production and inhibin production, activin augmented the effect of forskolin on all four parameters, whereas FSP significantly enhanced progesterone production without changing the other three parameters. Our findings suggest that activin action on rat granulosa cells may be mediated via regulation of cAMP generation. The action of FSP and FSH and/or activin-dependent, consistent with either an action as an activin binding protein or by a direct action of FSP on the granulosa cells. PMID- 1936551 TI - Involvement of a chondroitin sulfate proteoglycan in the avoidance of chick epidermis by dorsal root ganglia fibers: a study using beta-D-xyloside. AB - In 7-day chick embryo dorsal root ganglia and epidermis cocultures, nerve fibers avoid the epidermis. Previous studies have indicated that glycoproteic factors, secreted by epidermis, could be involved in this phenomenon. Treatment of epidermis by beta-D-xyloside, a specific proteoglycan synthesis inhibitor, abolishes the avoidance reaction. The same result is obtained when anti chondroitin sulfate antibodies are added to the culture medium. Using HPLC and 35SO4 labeling combined with chondroitinase and hyaluronidase treatment, it has been demonstrated that chondroitin sulfate is present in the epidermal conditioned medium. This suggests that a chondroitin sulfate proteoglycan secreted by the epidermis is implicated in the neurite avoidance reaction and that epidermis could therefore control its own "noninnervation". In vivo, inhibitory influences by local extracellular components may control the guidance of growth cones during nerve pattern formation. PMID- 1936552 TI - The cloning and characterization of a maternally expressed novel zinc finger nuclear phosphoprotein (xnf7) in Xenopus laevis. AB - We report the cloning of a cDNA (xnf7) coding for a maternally expressed Xenopus protein that becomes highly enriched in nuclei of the central nervous system during later development and in nuclei of adult brain. The protein also shows stage-specific nuclear/cytoplasmic partitioning and phosphorylation that may be related to its function. In addition, it binds to double-stranded DNA in vitro. The conceptual protein produced by the xnf7 clone contains several acidic domains, a novel zinc finger domain, three putative p34cdc2 protein kinase phosphorylation sites, and a bipartite basic nuclear localization signal. The xnf7 mRNA was detected as a maternal transcript that decreased in abundance during development through the gastrula stage. It was reexpressed at the neural stage in mesoderm and neural tissues, and its reexpression was not dependent upon the normal juxtaposition of the mesoderm and ectoderm that occurs during neural induction as demonstrated by high titer in exogastrulae. In situ hybridization showed enrichment of the mRNA in the neural tube and a small amount in the mesoderm at the late neurula stage. Xnf7 is normally phosphorylated during oocyte maturation. The bacterially expressed xnf7 protein was phosphorylated in vitro by purified maturation-promoting factor at a threonine in a small N-terminal domain containing one of the p34cdc2 protein kinase phosphorylation sites, but not by several other protein kinases. The structural domains present in the protein and its localization in nuclei suggest that the xnf7 gene product performs an important nuclear function during early development, perhaps as a transcription factor or a structural component of chromatin. PMID- 1936553 TI - Developmental regulation of fetal to adult globin gene switching in human fetal erythroid x mouse erythroleukemia cell hybrids. AB - Human fetal erythroid x murine erythroleukemia cell hybrids undergo human fetal (gamma) to adult (beta) globin gene switching in vitro under the control of a mechanism located on human chromosome 11. We investigated whether this mechanism acts in cis or in trans by preparing hybrid cells containing marked fragments of the gamma and beta genes known to switch in transgenic mice. In these cells the chromosomally introduced human globin locus undergoes the fetal to adult globin gene switch. In contrast, the marked globin gene fragments were expressed at all stages of hybrid development. These results suggest that either the mechanism of switching acts in cis or that sequences present in the chromosomal globin locus but missing from the transfected globin gene fragments mediate its action. PMID- 1936554 TI - Post-translationally modified tubulins in Artemia: prelarval development in the absence of detyrosinated tubulin. AB - The synthesis of post-translationally modified tubulins was examined during Artemia development. Tubulin, either purified to homogeneity or in cell-free extracts, was blotted to nitrocellulose and probed with a panel of antibodies. When purified tubulin was examined, tyrosinated tubulin underwent a large decrease as development progressed and this was accompanied by the appearance of detyrosinated tubulin in samples from organisms developed 24 hr. The inclusion of carboxypeptidase inhibitors had a small effect on the relative amounts of tyrosinated and detyrosinated tubulins in 24-hr preparations. The amount of alpha and beta-tubulin in cell-free extracts of Artemia either remained relatively constant during development or increased slightly. The same result was obtained for acetylated and tyrosinated tubulin. Detyrosinated tubulin first appeared in 24-hr cell-free extracts and was only post-translationally modified tubulin to increase, relative to the total amount of tubulin, as the brine shrimp developed. As revealed by immunofluorescence staining, detyrosinated tubulin occurred in many cell types of developing nauplii and was prominently displayed in mitotic figures. Artemia, a complex metazoan animal, is thus able to grow for an extended period of time in the absence of detyrosinated tubulin. This isoform is however, synthesized in early larvae and may be required for the development of elongated cells including those which encircle the gut. Detyrosination remains as the only developmentally related change observed for brine shrimp tubulin. PMID- 1936555 TI - In vivo protein phosphorylation and labeling of ATP in sea urchin eggs loaded with 32PO4 via electroporation. AB - Protein phosphorylation was examined in sea urchin eggs in which the ATP was labeled with 32P over a brief period of time using reversible electrical poration to gain access to the cytoplasm. Unfertilized eggs from two species, Lytechinus pictus and Strongylocentrotus purpuratus, were electrically permeabilized and incubated in the presence of [32P]H3PO4, under conditions allowing label uptake. After a 5-min loading period the eggs were resealed and the fate of the label was monitored. The label had equilibrated with the cellular ATP pool within the 13 min period required for loading and resealing the eggs. Furthermore, this equilibrium was maintained for at least 2 hr beyond the loading period in either unfertilized or fertilized eggs (i.e., the specific activity of ATP was the same for fertilized and unfertilized eggs). We also examined the position of the label within the ATP and found that 40-45% of the label isolated with the ATP was in the gamma phosphate of ATP and hence was immediately available for protein phosphorylation. The label was maintained in this position in the ATP for at least 2 hr following the loading period and was not affected by fertilization (determined for L. pictus only). The phosphoprotein banding pattern was determined by gel electrophoresis and autoradiography at various time points following the loading period. There was a continuous increase of label incorporated into protein over time; however, the banding pattern did not change. This pattern was not affected by fertilization. Furthermore, inhibition of protein synthesis (with emetine) had no effect on this phosphoprotein banding pattern. Although the loading period was brief there was sufficient incorporation of label into protein during this time to obscure potential regulatory phosphorylation events. PMID- 1936556 TI - The transcription factor, Egr-1, is rapidly modulated in response to retinoic acid in P19 embryonal carcinoma cells. AB - The pluripotent murine embryonal carcinoma cell line, P19, differentiates along at least three main pathways under the inductive influence of retinoic acid (RA). The events most critical to the establishment of a particular differentiation pathway must occur early since P19 cells are committed to differentiation pathways after 30 min of exposure to RA (M. W. McBurney, personal communication and our unpublished results). We have, therefore, looked for genes that are induced (or repressed) within 30 min of RA addition and find that Egr-1 is one of these genes. Egr-1 is a transcription factor of the zinc-finger class and is known to transactivate genes after binding to specific oligonucleotide sequences. We describe here the extremely rapid and transient increase of Egr-1 transcript and protein levels in P19 cells after RA addition. Stable induction of Egr-1 transcripts occurred in the presence of protein synthesis inhibitors. Simultaneous addition of RA and cycloheximide did not result in an additive effect. The mechanism of induction with either drug appears to involve relief of a block to transcriptional elongation. The response was more rapid at high RA concentrations and this suggests that the Egr-1 transcription factor could play a role in initiation of differentiation pathways of P19 EC cells. PMID- 1936557 TI - Mutations in a steroid hormone-regulated gene disrupt the metamorphosis of the central nervous system in Drosophila. AB - The actions of steroid hormones on vertebrate and invertebrate nervous systems include alterations in neuronal architecture, regulation of neuronal differentiation, and programmed cell death. In particular, central nervous system (CNS) metamorphosis in insects requires a precise pattern of exposure to the steroid molting hormone 20-hydroxyecdysone (ecdysterone). To test whether the effects of steroid hormones on the insect nervous system are due to changes in patterns of gene expression, we examined Drosophila mutants of the ecdysterone regulated locus, the Broad Complex (BR-C). This report documents aspects of CNS reorganization which are dependent on BR-C function. During wild-type metamorphosis, CNS components undergo dramatic morphogenetic movements relative to each other and to the body wall. These movements, in particular, the separation of the subesophageal ganglion from the thoracic ganglion, the positioning of the developing visual system, and the fusion of right and left brain hemispheres, are deranged in BR-C mutants. In addition, a subset of mutants shows disorganization of optic lobe neuropil, both within and among optic lobe ganglia. Optic lobe disorganization is found in mutants of the br and l(1)2Bc complementation groups, but not in those of the rbp complementation group. This suggests that the three complementation groups of this complex locus represent distinct but overlapping functions necessary for normal CNS reorganization. This study demonstrates that ecdysterone-regulated gene expression is essential for CNS metamorphosis, illustrating the utility of Drosophila as a model system for investigating the genetic basis of steroid hormone action on the nervous system. PMID- 1936558 TI - Sequence and developmental expression of a mRNA encoding a putative protein of rat sperm outer dense fibers. AB - We have isolated a cDNA from rat testis homologous to the Drosophila melanogaster gene mst(3)gl-9 by screening a rat testis cDNA library with mst(3)gl-9 and by direct PCR amplification of upstream sequences out of the cDNA library. Homologous genes are also expressed in testes of different mammalian species. In rat testis, two different transcripts are found. Evidences are presented which suggest that these two transcripts are alternative splicing products. As proved by Northern blot analysis of testis RNA prepared from rats of different ages and by in situ hybridization to rat testis tissue sections, the mRNAs are first transcribed in early spermatids. The longest open reading frame of the cDNA encodes a polypeptide of 244 amino acids which contains 16.4% cysteine, 9.9% proline, and 5.7% glycine and closely resembles the sizes and amino acid compositions of two major polypeptides isolated from outer dense fibers of rat spermatozoa. The COOH-terminal end consists mostly of the tripeptide motif Cys Gly-Pro, the main motif in D. melanogaster mst(3)gl-9. It is suggested that the isolated rat cDNA encodes a polypeptide which is a protein component of the outer dense fibers of spermatozoa. PMID- 1936559 TI - Cortical morphogenesis in Paramecium: a transcellular wave of protein phosphorylation involved in ciliary rootlet disassembly. AB - In Paramecium, the morphogenesis of the cortex at cell division, which assures reconstruction of shape and surface pattern, has been shown to involve transcellular signals which spread across the cortex like a wave, originating principally from the oral apparatus. One of the events these signals control is the reorganization of the ciliary rootlets through a cycle of regression and regrowth. The ciliary rootlets are nucleated on the ciliary basal bodies and form a scaffold extending over the entire cell surface that is important in aligning the basal bodies and the unit territories organized around them in longitudinal rows. We present evidence that the mechanism underlying their reorganization is cell-cycle-dependent phosphorylation of the structural proteins which compose the ciliary rootlets. We have isolated the rootlets and prepared a polyclonal antibody against them. In situ immunofluorescence of dividing cells with the anti rootlet antibody, and with the monoclonal antibody MPM-2 specific for phosphoproteins shows that a wave of phosphorylation of the ciliary rootlets spreads across the cell at division and just precedes their regression. Two dimensional Western blot analysis of cytoskeleton and isolated rootlets along with alkaline phosphatase treatment demonstrates that the rootlets are composed of phosphoproteins, while experiments with interphase and dividing cells provide direct evidence that hyperphosphorylation of these proteins at division brings about disassembly of the structure. PMID- 1936560 TI - The fub-1 mutation blocks initial myofibril formation in zebrafish muscle pioneer cells. AB - The earliest muscle in zebrafish arises from iterated sets of two to six cells in each somite, the muscle pioneers (MP). MP develop synchronously in young trunk myotomes adjacent to the notochord, precisely where the horizontal myoseptum will form. They elongate without cell fusion and differentiate hours earlier than surrounding cells, thus providing a simple and accessible system for in vivo study of myogenesis and muscle patterning. Before the MP form definitive myofibrils they assemble long bundles of actin-containing filaments, similar to "stress-fiber-like structures" reported by others. In fub-1 mutants, in which myofibrils are disorganized in all skeletal muscle cells, the MP appear and elongate normally, but ordered actin filament bundles are not seen. This defect could underlie the later myofibrillar ones, consistent with the proposal that actin filament bundles are essential for proper formation of the muscle contractile apparatus. PMID- 1936561 TI - Uvomorulin mediates calcium-dependent aggregation of islet cells, whereas calcium independent cell adhesion molecules distinguish between islet cell types. AB - Rat islets of Langerhans are organized as a core of B-cells surrounded by non-B cells. It is believed that cell type segregation during histogenesis is the result of the differential expression of cell adhesion molecules (CAMs). Since we have previously shown that in contrast to non-B-cells, homotypic adhesion of pancreatic B-cells is dependent on the presence of Ca2+, the possibility exists that Ca(2+)-dependent CAMs (cadherins) might be in part responsible for islet topography. We now demonstrate that after selective removal of Ca(2+)-independent CAMs from the surface of islet cells by mild trypsin/Ca2+ digestion (TC treatment), there is no significant difference in homotypic adhesion between sorted B- and non-B-cells in the presence of calcium, suggesting an identical deployment of cadherins. Flow cytometric analysis reveals high levels of uvomorulin on both B- and non-B-cells, without any difference between the two populations. On a "1 to 100" scale, B-cell aggregation in the presence of Ca2+ was decreased by anti-uvomorulin Fab fragments from 67 +/- 4 to 25 +/- 3 (mean +/ SEM, n = 4, P less than 0.01). This level is not different from the degree of B cell aggregation seen in the presence of 0.5 mM EDTA (22 +/- 2). Aggregation of non-B-cells was only slightly decreased by anti-uvomorulin Fab fragments (from 69 +/- 3 to 52 +/- 4). However, after TC-treatment, homotypic cell aggregation of both B- and non-B-cells was completely inhibited by anti-uvomorulin Fab fragments. Thus, uvomorulin appears to be the only functional cadherin on islet cells, and cell type aggregation properties diverge only by virtue of higher levels of Ca(2+)-independent CAMs on non-B-cells. Fab fragments with the property of perturbing islet cell aggregation in the absence but not in the presence of calcium also prevented pseudoislet organization in vitro, suggesting that Ca(2+) independent CAMs play the major role in islet cell type segregation. In conclusion, the results show that uvomorulin is responsible for the Ca(2+) dependent aggregation of islet cells and suggest that the cellular organization within islets or pseudoislets results from the different level of Ca(2+) independent CAMs on islet cell types. PMID- 1936562 TI - Cardiac differentiation induced by dopamine in undifferentiated cells of early chick embryo. AB - Evidence suggests that neurotransmitters can act as possible chemical signals involved in cell division and morphogenetic movements long before neurons appear in the embryo. However, whether they are playing a role in differentiation is now unknown. It was recently observed (M. Sarasa and S. Climent, 1987, J. Exp. Zool. 241, 181-190) that the neurotransmitter dopamine exerted a stimulating effect on cardiac differentiation in the chick in ovo. We show here that dopamine acts as a specific inducer of heart muscle differentiation in vitro. When cells of the gastrula of embryos treated with dopamine were dissociated and reaggregated, the aggregates obtained almost entirely underwent cardiac muscle differentiation. Also, when small postnodal pieces obtained from the most posterior region of the gastrula were cultivated in the presence of dopamine, they differentiated into myocardic tissue instead of following their fate map. Therefore, dopamine can trigger a process that both causes undifferentiated cells to differentiate into heart muscle and compels cells already determined to another way of differentiation to become myocardic tissue. PMID- 1936563 TI - Myoblasts from fetal and adult skeletal muscle regulate myosin expression differently. AB - We compared the expression of myosin heavy chains in myogenic cultures prepared from fetal (embryonic Day 10) and adult (12-16 weeks) chicken pectoralis muscle using immunofluorescence with isoform-specific monoclonal antibodies. We found that the majority of fetal myocytes (differentiated myoblasts) and myotubes coexpressed ventricular and embryonic myosin heavy chains in culture. Also, when fetal cells were plated at a clonal density most clones coexpressed both ventricular and embryonic isoforms. In contrast, all adult myocytes and newly formed adult myotubes expressed just ventricular myosin, whether plated at mass or clonal densities. Within 12-24 hr of the onset of fusion, adult myotubes began to express embryonic myosin as well. Eventually, the majority of adult myotubes coexpressed both ventricular and embryonic myosin. The delay of embryonic myosin expression until after fusion was also seen in passaged adult myoblasts and in myoblasts isolated from regenerating adult muscle. The expression of embryonic myosin can be abolished by inhibiting fusion with EGTA in adult but not in fetal cultures. We conclude that both fetal and adult myotubes express ventricular and embryonic myosins but only fetal myocytes express the embryonic isoform prior to fusion. This difference in the regulation of embryonic myosin expression between fetal and adult myoblasts supports the hypothesis that these cells may represent two distinct populations of myogenic precursors. PMID- 1936564 TI - Primary mesenchyme cells of the sea urchin embryo require an autonomously produced, nonfibrillar collagen for spiculogenesis. AB - A collagen molecule in the sea urchin embryo was characterized by analysis of a 2.7-kb cDNA clone. This clone, Spcoll, was obtained by screening a gastrula stage Strongylocentrotus purpuratus cDNA library with a 237-bp genomic clone encoding a collagen-like sequence previously isolated by Venkatesan et al. (1986). DNA sequence analysis of the cDNA clone demonstrated the nonfibrillar nature of the encoded molecule--13 interruptions of the Gly-X-Y repeat motif were found in the 85-kDa open reading frame. The mRNA of approximately 9 kb accumulated specifically in mesenchyme cells of the embryo through development to the pluteus larva. Polyclonal antibodies generated against a Spcoll-beta-galactosidase fusion protein were utilized to identify and localize the native Spcoll. This collagen molecule of approximately 210 kDa was deposited into the blastocoel by the primary mesenchyme cells. When primary mesenchyme cells were cultured in vitro, Spcoll was secreted into the media and accumulated at sites of cell-substrate interaction. Addition of anti-Spcoll antibodies to primary mesenchyme cell cultures selectively inhibited spiculogenesis, whereas other antibodies had no inhibitory effect. Since collagen is not a component of the organic matrix of spicules (Benson et al., 1986), these results suggest that the autonomous production of Spcoll by differentiating mesenchyme cells in turn influences the point in differentiation at which these cell initiate biomineralization. PMID- 1936565 TI - Isolation and characterization of developmentally regulated sea urchin U2 snRNA genes. AB - Genes encoding the U2 snRNA have been isolated from the sea urchins, Strongylocentrotus purpuratus and Lytechinus variegatus. Representatives of tandemly repeated gene sets have been isolated from both sea urchin species and a unique U2 gene has also been isolated from L. variegatus. The sequence of the U2 snRNA encoded by the tandemly repeated genes differs in two nucleotides between S. purpuratus and L. variegatus. The unique U2 gene from L. variegatus encodes the same U2 RNA as the tandemly repeated genes. There is a change in the U2 genes expressed between morula and pluteus embryos as judged by a change in the U2 RNA sequence in S. purpuratus embryos. The tandemly repeated genes were expressed at a higher rate in blastula than in gastrula stage relative to the single-copy gene, when the two genes were injected into sea urchin zygotes. PMID- 1936566 TI - Characterization of the ooplasmic factor inducing decondensation of and protamine removal from toad sperm nuclei: involvement of nucleoplasmin. AB - Immunohistochemical studies with antiserum against the protamines of the toad, Bufo japonicus, revealed that the sperm nucleus loses protamines within 5 min after entry into the egg. Likewise, lysolecithin-permeabilized sperm incubated with the egg extract lose the protamines within 1 min, accompanied by nuclear decondensation. The activities that induce both protamine removal and decondensation in sperm nuclei were found in extracts from growing and mature oocytes and pregastrula embryos, but not in postneurula embryos or adult tissues. SDS-PAGE analyses revealed that the egg extract removed not only protamines from the Bufo sperm, but also selectively the sperm-specific basic proteins from sperm nuclei of Xenopus laevis. The protamine-removing activity (PRA) was partially purified from egg extracts as negatively charged macromolecules by anion-exchange chromatography and gel filtration. The PRA was heat-stable (100 degrees C, 10 min) and sensitive to proteinase K, but not to RNase A and DNase I. Immunoblot analysis of the supernatant after incubation of Bufo sperm in the fraction with the PRA revealed that protamines derived from sperm nuclei were associated with a major protein of the fraction. This protein exhibited mobilities of 140 and 36 kDa on native- and SDS-PAGE, respectively, with the isoelectric points in the range 4.2 to 4.5 and possessed an amino acid composition quite similar to that reported for Xenopus nucleoplasmin. We propose that in fertilized eggs the protamines are removed from sperm nuclei by nucleoplasmin by binding to but not by enzymatic degradation of the protamine. PMID- 1936567 TI - Extracellular Mg2+ induces a loss of microvilli, membrane retrieval, and the subsequent cortical reaction, in the oocyte of the prawn Palaemon serratus. AB - Surface changes induced by sea water were analyzed in the ovulated oocyte of the prawn Palaemon serratus. They depended on the presence of external Mg2+ but not on external Ca2+ alone. Increasing external Mg2+ from 0 mM to 30 mM stimulated first a progressive disappearance of preexisting microvilli, which was over within 30 min of incubation. This is correlated with membrane removal via internalization of coated vesicles, ascertained by observations of endocytosis of an extracellular fluid-phase marker and by measurement of a diminution in membrane capacitance (Cm). Thirty-five minutes after sea water contact, the prawn oocyte underwent a cortical reaction independent of fertilization. It consists in a heavy exocytosis of ring-shaped elements, leading to the deposition of a thick capsule, and requiring a threshold Mg2+ concentration of greater than or equal to 10 mM and at least a 3-min incubation with Mg2+. Concurrently, the values of the membrane capacitance (Cm) and conductance (Gm) increased about 2 and 10 times their initial values, respectively. The calcium ionophore ionomycin, added to Mg(2+)-free artificial sea water, stimulated the cortical reaction with requirement of external Ca2+. Other divalent cations (Mn2+, Zn2+, Co2+, Ni2+, Cd2+) instead of Mg2+, induced the cortical reaction, but Ba2+, Sr2+, and La3+ did not. When eggs are fertilized, the cortical reaction takes place in two steps, the first being a discrete exocytosis of a foamy material and the second always involving ring-shaped elements. PMID- 1936568 TI - Fiber regeneration is not persistent in dystrophic (MDX) mouse skeletal muscle. AB - Fiber replacement has been measured in adult mdx mouse limb skeletal muscles. During the first 10 days after birth all fibers appear normal; between Week 3 and 4 there is massive fiber degeneration followed by regeneration in which close to 100% of the fibers are repaired or replaced. New fibers arising in adult mice are characterized by expression of fetal myosin mRNAs in whole muscle extracts, and by staining of individual fibers with an embryonic myosin heavy chain-specific antibody. By 10 weeks of age new fiber replacement rate, indicated by frequency of fibers reacting with antibody, is reduced to about 10%, and by 1 year of age less than 1% of the fibers are being replaced at rates above control. Total fiber number also remains fairly constant. We conclude that the fibers regenerating up to 10 weeks of age become stabilized and do not undergo further rounds of degeneration and regeneration. This is consistent with the observed benign phenotype of adult mdx animals and with the idea that once-regenerated fibers escape the catastrophic dystrophic phenotype by acquiring a function that compensates for their mdx mutation. The mechanism by which regenerated mdx fibers restore adequate function in the absence of dystrophin may, when understood, provide clues to effective nongenetic interventions for muscular dystrophy in humans where regenerated fibers continue to degenerate and where the disease is often fatal. PMID- 1936569 TI - Induction of retinal regeneration in vivo by growth factors. AB - We have previously reported that basic fibroblast growth factor (bFGF) can induce retinal regeneration in the stage 22-24 chicken embryo. The present study was undertaken to identify the cellular source of the regenerate and to determine whether other growth factors also elicit regeneration in this animal model. Polymer implants containing bFGF were inserted into eyes of chicken embryos immediately after extirpation of the neural retina. The retinal pigment epithelium (RPE) was left intact. Evaluation by light microscopy revealed that in bFGF-treated eyes the new neural retina arose by transdifferentiation of the entire RPE layer. Differentiation of the new neural retina occurred in a sequence similar to that of normal development but proceeded in a reverse (vitread) direction. All retinal laminae had differentiated by Day 15. However, the regenerate displayed reversed polarity, with photoreceptors closest to the lens. The RPE, pecten, and optic nerve were absent. Focal areas of degeneration in the retinal regenerate became evident for the first time on Day 10. Retinal regeneration was also observed after treatment with higher doses of acidic fibroblast growth factor, but not with nerve growth factor-beta, transforming growth factor-beta 1, insulin, or insulin-like growth factors I or II. These results raise the possibility that FGFs may play a role in retinal differentiation during development. PMID- 1936570 TI - The oblique muscle organizer in Hirudo medicinalis, an identified embryonic cell projecting multiple parallel growth cones in an orderly array. AB - The oblique muscle layer in the leech body wall is built upon the processes of a unique identified embryonic cell, the Comb- or C-cell. Each C-cell is composed of a spindle-shaped soma that projects approximately 70 parallel processes through the developing body wall at an angle oblique to the long axis. The morphogenesis of this cell and the navigation of its growth cones were examined by intracellular dye filling and antibody staining. At the earliest stages described each C-cell had about six processes, with those near the center of the cell oriented obliquely. As processes were added at the axial ends of the soma they often projected along previously developed longitudinal or circular muscle founder cells and then secondarily aligned themselves parallel to the older processes from the same C-cell. All growth cones initially extended to a particular location in the body wall, where they ceased growing until all 70 processes had been added (over the course of about 5 days). As adjacent segmental homologs met, their growth cones intermingled, eventually sorting out to align parallel. When one of these cells was ablated early--but not later--in development, the remaining adjacent segmental homologs expanded into the vacant territory, consistent with a hypothesis of mutual avoidance between segmental homologs. Most processes that expanded into the experimentally induced vacancy remained correctly oriented and parallel; the few exceptions projected instead along the mirror-image trajectory. Thus, expression of specific avoidance between adjacent C-cell processes is developmentally regulated and functions as a guidance mechanism in vivo, in that it serves to restrict possible trajectories. After aligning its growth cones, each cell stopped adding processes and the processes rapidly extended in concert along relatively precise trajectories. Processes of contralateral homologs cross to form the orthogonal grid used as a scaffold by myocytes to form the oblique muscles. The advancing fronts of growth cones reached the dorsal midline at about the same time as body closure occurs (at about Embryonic Day 20) at which time the C-cells became granular, lost processes, and presumably died. This sequence of developmental events is consistent with temporal and spatial regulation of different morphogenetic strategies, including--but not limited to--specific avoidance, and further suggests testable hypotheses of mechanisms of growth cone navigation in the intact embryo. PMID- 1936571 TI - Identification and characterization of a ventricular-specific avian myosin heavy chain, VMHC1: expression in differentiating cardiac and skeletal muscle. AB - To investigate the initial differentiative processes of avian cardiac and skeletal myogenesis, we have isolated and characterized a molecular marker of the cardiac myocyte cell lineage, ventricular myosin heavy chain 1 (VMHC1). Our goal in this initial study was to use a gene-specific probe to analyze the expression pattern of VMHC1 RNA during development. DNA sequence analysis confirmed that VMHC1 represented a novel member of the MHC gene family. PCR analysis using gene specific primers determined that the VMHC1 RNA is first expressed in the stage 7 cardiac primordia, much earlier than the appearance of a tubular beating heart. RNA blot analyses determined that the VMHC1 message was present in the embryonic and adult ventricles but not in the embryonic or adult atria or skeletal muscle tissues of either the fast or slow type after definitive muscle structures were formed. Still, PCR and in situ hybridization analyses of the initial phases of cardiac and skeletal myogenic differentiation determined that VMHC1 was expressed in both progenitor populations at the initiation of myogenesis regardless of the source of myoblast or site of initial differentiation. The transient expression in skeletal muscle precursors coincided with the onset of differentiation in these cells. These data suggest that the differentiative programs of cardiac and skeletal myocytes overlap during their initial phases, then quickly become distinct. The VMHC1 gene should provide a model for identification of transcription factors involved in cardiac myocyte differentiation. PMID- 1936572 TI - Ryanodine receptor protein is expressed during differentiation in the muscle cell lines BC3H1 and C2C12. AB - BC3H1 and C2C12, murine cell lines, were assessed as model systems for the expression of ryanodine receptor protein during myogenesis. The ryanodine receptor is a calcium release channel of the sarcoplasmic reticulum and a component of the triad junction, a structure which is essential to excitation contraction coupling in mature striated muscle. BC3H1 and C2C12 cells do not express the ryanodine receptor at detectable levels in a proliferative, nondifferentiated state. The ryanodine receptor protein is expressed during differentiation in BC3H1 and C2C12 cells, becoming detectable within 24 hr of the onset of differentiation. In both cell lines the ryanodine receptor is assembled in oligomeric form and binds [3H]ryanodine with high affinity. Fusion is not required for expression of the ryanodine receptor in either BC3H1 or nonfusing C2C12 cells. The level of expression of the ryanodine receptor protein is modulated by incubation with the growth factors TGF-beta and bFGF in a manner similar to that of other muscle-specific proteins. These initial observations suggest that the BC3H1 and C2C12 cell lines provide a model system for further investigations of the expression and function of the ryanodine receptor during myogenic differentiation. PMID- 1936573 TI - Colocalization of N-CAM and N-cadherin in avian skeletal myoblasts. AB - The cell-cell adhesion molecules, N-CAM and N-cadherin, have been shown previously to mediate myoblast interaction during cell fusion accompanying skeletal myogenesis. To study the localization of both molecules in fusion competent myoblasts, we used antigen-specific primary antibodies and a double labeling preembedding immuno-electron microscopy technique. Ultrastructural observations and quantitative analysis of the results reveal that N-CAM and N cadherin frequently colocalize in clusters on the myoblast plasma membrane. The data provide morphological evidence that the two adhesion glycoproteins cooperate in mediating myoblast interaction during myoblast fusion. PMID- 1936574 TI - Characterization of sea urchin egg endoplasmic reticulum in cortical preparations. AB - The cortical endoplasmic reticulum (ER) of sea urchin eggs was localized on isolated egg cortices by staining with aqueous suspensions of the dicarbocyanine "DiI." Immunofluorescence localization of a calsequestrin-like protein was essentially identical; this is consistent with a role for the ER in calcium regulation. The ER often encircles cortical granules, making it well-suited for initiating fusion and propagating the calcium wave. Thiazole orange and Hoechst dye 33258 at pH 2 stain ribosomes bound to the ER, providing evidence that the cortical ER is rough ER. High chloride concentrations were found to disrupt ER continuity. PMID- 1936575 TI - Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo. AB - Bandeiraea simplicifolia B4 isolectin (BSLB4) and polyclonal antisera against von Willebrand factor (VWF) were used to study the origin of endothelial cells and their organization into blood vessels in the postimplantation mouse embryo. Examination of BSLB4-stained whole mounted and sectioned embryos revealed intense staining of the endothelium, highlighting large vessels, capillaries, and many individual cells. Dorsal aorta formation was first obvious at E7 when many lectin positive cells appeared in paraxial and lateral plate mesoderm. As development proceeded to E8, BSLB4-positive cells became organized into craniocaudal lines destined to become the aorta proper. At E9, BSLB4 stained all vessels of the embryo including the dorsal aorta, the intersomitic arteries, and the endocardium. VWF expression was not detected until E8 when BSLB4/VWF double stained sections revealed the dorsal aortae as the first VWF-positive vessels, while other endothelium visible with BSLB4 remained negative for VWF immunostaining. By E12 many other vessels became VWF-positive, including the aortic arches, the intersomitic arteries, and the cardinal veins. However, many angioblasts and capillaries remained VWF-negative, reflecting the heterogeneous expression of VWF among endothelium that has been reported in adults of other species. The histochemical data reported here support the conclusions of earlier avian studies by showing distinct vascular patterns in the initial formation of vessels from isolated angioblasts (vasculogenesis), followed by the extension and organization of the initial vascular structures (angiogenesis). Moreover, our data suggest that the endothelium arises from distinct VWF-positive sources associated with the dorsal aorta, as well as VWF-negative sources associated with other vessels in the embryo. PMID- 1936576 TI - Epithelial-mesenchymal interactions in uterus and vagina alter the expression of the cell surface proteoglycan, syndecan. AB - The cell surface proteoglycan, syndecan, exhibits molecular and histological dimorphism in the mouse uterus and vagina. In the mature vagina, syndecan is localized at the surfaces of the basal and intermediate cells of the stratified epithelium and has a modal molecular mass of ca. 92 kDa. The uterus expresses a larger form of syndecan (ca. 110 kDa) which is detected at the basolateral surfaces of the simple columnar epithelial cells. We have investigated whether epithelial-mesenchymal interactions influence the expression of syndecan in these organs by analyzing tissue recombinants composed of mouse epithelium and rat mesenchyme or vice versa with monoclonal antibody 281-2, which recognizes mouse syndecan. In tissue recombinants composed of newborn mouse uterine epithelium and rat vaginal stroma, the uterine epithelium was induced to form a stratified vaginal epithelium which expressed syndecan in same the pattern and mass typical of vaginal epithelium. Likewise, rat uterine stroma induced newborn mouse vaginal epithelium to undergo uterine development, and this epithelium exhibited a uterine pattern of syndecan expression. Although stromal cells normally express little syndecan in most adult organs, analysis of recombinants composed of mouse stroma and rat epithelium revealed that both uterine and vaginal mouse stromata synthesized syndecan that was larger (ca. 170-190 kDa) than the epithelial syndecans. A quantitative increase in the amount of stromal syndecan was evident when stroma was grown in association with epithelium in comparison to stroma grown by itself. These data suggest that epithelial-mesenchymal interactions influence the amount, localization, and mass of both epithelial and stromal syndecan. PMID- 1936577 TI - Nascent protein requirement for completion of meiotic maturation and pronuclear development: examination of fertilized and A-23187-activated surf clam (Spisula solidissima) eggs. AB - The involvement of newly synthesized proteins and calcium in meiotic processes, sperm nuclear transformations, and pronuclear development was examined in emetine treated, fertilized, and A-23187-activated Spisula eggs by observing changes in the morphogenesis of the maternal and paternal chromatin. Emetine treatment (50 micrograms/ml) initiated 30 min before fertilization or A-23187 activation inhibited incorporation of [3H]leucine into TCA-precipitable material and blocked second polar body formation. Sperm incorporation and the initial enlargement of the sperm nucleus were unaffected; however, the dramatic enlargement and transformation of the sperm nucleus into a male pronucleus, which normally follow polar body formation, were delayed 10 to 20 min. Unlike the situation in untreated, control eggs, male pronuclear development took place while the maternally derived chromosomes remained condensed. It was not until approximately 20 min after the normal period of pronuclear development that the maternal chromosomes dispersed and formed a female pronucleus in emetine-treated, fertilized eggs. Formation of pronuclei, however, was unaffected in both emetine treated, A-23187-activated eggs and fertilized eggs incubated with A-23187. These observations indicate that germinal vesicle breakdown, first polar body formation, and initial transformations of the sperm nucleus are independent of newly synthesized proteins. Inhibition of second polar body formation and the delay in pronuclear development brought about by emetine, as well as the appearance of silver grains over pronuclei in autoradiographs of control eggs incubated with [3H]leucine demonstrate that nascent proteins are involved with the completion of meiotic maturation and the development of male and female pronuclei. The ability of A-23187 to override the inhibitory effects of emetine on pronuclear development suggests that both nascent protein and calcium signals are involved in regulating the status of the maternal and paternal chromatin during pronuclear development. PMID- 1936578 TI - In vitro clonal analysis of quail cardiac neural crest development. AB - The developmental potentials of cardiac neural crest cells were investigated by in vitro clonal analysis. Five morphologically distinct types of clones were observed: (1) "pigmented" clones contained melanocytes only; (2) "mixed" clones consisted of pigmented and unpigmented cells; (3) "unpigmented dense" clones consisted of flattened, closely aligned unpigmented cells; (4) "unpigmented loose" clones consisted of a few loosely arranged, flattened cells; and (5) "unpigmented large" clones included a large number of small, stellate cells that were highly proliferative. The binding patterns of antibodies against lineage specific markers showed that cells in the different clones expressed characteristic phenotypes. The following phenotypes were expressed in addition to pigment cells: smooth muscle cells, connective tissue cells, chondrocytes, and cells in the sensory neuron lineage. Mixed clones expressed all five phenotypes. Unpigmented dense clones contained smooth muscle cells, connective tissue cells, chondrocytes, and sensory neurons. Unpigmented loose clones exclusively consisted of smooth muscle cells, whereas unpigmented large clones contained chondrocytes and sensory neuron precursors. Based on these results, the following conclusions can be drawn: (1) Pigmented and unpigmented loose clones are most likely formed by precursors that are committed to the melanogenic and myogenic cell lineages, respectively. (2) Mixed and unpigmented dense clones are derived from pluripotent cells with the capacity to give rise to four or five phenotypes. (3) Unpigmented large clones originate from progenitor cells that appear to have a partially restricted developmental potential, that is, these cells are capable of generating two phenotypes in clonal cultures. Thus, the data indicate that the early migratory cardiac neural crest is a heterogeneous population of cells, consisting of pluripotent cells, cells with a partially restricted developmental potential, and cells committed to a particular cell lineage. PMID- 1936579 TI - Individual olfactory signatures as major determinants of early maternal discrimination in sheep. AB - Responses of recently parturient ewes to their familiar versus separated (i.e., unfamiliar) twin lambs were observed in an attempt to elucidate further the characteristics of the phenotypic traits (signatures) mediating maternal recognition and bonding. Ewes responded more positively to their familiar lamb than to its twin that had been isolated at birth. Nonetheless, those same mothers also discriminated between their separated twin and unfamiliar alien lambs. Alien lambs elicited similar rejection behavior regardless of whether they had been housed with their own mother or in isolation prior to testing. Lambs appear to have individually distinct (olfactory) signatures; however, the signatures of twin siblings may be sufficiently similar to enable the mother to detect a resemblance. No evidence suggests that acquired maternal labels play a role in either the acceptance of the ewe's own lamb(s) or rejection of aliens. PMID- 1936580 TI - Time-dependent effects of peer separation on lymphocyte proliferation responses in juvenile squirrel monkeys. AB - This study evaluated the immunological, hormonal, and behavioral responses of juvenile squirrel monkeys to repeated social separations of varying length. Following a 3-hr separation, lymphocyte responses to stimulation with the mitogen concanavalin A (Con A) declined significantly, and these alterations were sustained after a 24-hr separation period. The responses to Con A and to a second mitogen, phytohemagglutinin (PHA), were suppressed after 2 days. At the end of a 7-day separation period, immune responses were not significantly different from basal values. Plasma cortisol levels were elevated above basal levels in all animals after the 3-hr, 24-hr, and 2-day separations, but were not elevated after the 7-day separation. While we observed no statistically significant changes in locomotor activity or calling behavior during any of the separations, the monkeys tended to be most active and to call most immediately following separation. Our findings concur with earlier reports indicating that social stressors can influence lymphocyte proliferation in nonhuman primates and that certain cell types might be differentially sensitive to stress, but also indicate that these influences are transient. PMID- 1936581 TI - Associative processes in differentially reared rhesus monkeys (Macaca mulatta): blocking. AB - Nine isolate and 6 socially reared adult rhesus monkeys were examined in a standard blocking procedure. A tone was paired with a startle stimulus (US) during Phase 1. A tone-light compound CS was paired with a US during Phase 2. In Phase 3, the light was presented alone to test for blocking. Results showed that learning about the light was blocked in social controls, but not in isolates. These data suggest isolates processed information atypically, in that they developed an association to a redundant cue. A second group of isolates (n = 3) underwent the identical procedures. However, conditioned reactions to the tone were extinguished before testing. Test responding was significantly reduced in this group, that is, blocking was obtained. These data suggest the within compound association developed during Phase 2 mediated the isolate blocking deficit. Together, these findings imply long-term intellectual consequences of early social impoverishment. Such deficits may be mediated by alterations in central dopamine systems. PMID- 1936582 TI - Multiple functions of context during conditioning: a developmental analysis. AB - Contextual stimuli may influence conditioned behavior in at least two ways (e.g. Bouton & Bolles, 1985). By becoming associated with the unconditioned stimulus (US), context cues can acquire excitatory strength that facilitates responding to a phasic conditioned stimulus (CS). The context also can function to clarify the meaning of an ambiguous CS. Data obtained with an appetitive Pavlovian conditioning paradigm suggest that the processes mediating these two influences of context are dissociated during development. Evidence of context-US associations was observed in rats that began training on Postnatal Day 17, but no evidence for a disambiguation function was found until pups were 20- to 23-days old. Evidence for a context-US association was obtained by demonstrating that US alone presentations in the training context restored conditioned responding to an extinguished CS. Evidence for a disambiguation function was obtained by demonstrating that a context shift, concurrent with extinction of responding to a phasic CS, preserved responding to the CS when the subjects were subsequently tested in the training context. These findings were discussed in relation to (a) the development of the rat's ability to use relational representations, and (b) Nadel and Zola-Morgan's (1984) hypothesis linking hippocampal maturation to the role of context during development. PMID- 1936583 TI - Ontogeny of preference and aversion to salt in Fischer 344 rats and Syrian hamsters. AB - Fischer 344 (F344) rats and Syrian hamsters, unlike rats of the Sprague-Dawley or Wistar strains, exhibit an aversion to dilute NaCl solutions as adults. In the present studies, using the anterior intraoral infusion method, it is shown that both F344 rats and hamsters accept more dilute NaCl than either water or concentrated NaCl (i.e., show a "single bottle" preference/aversion function identical to Sprague-Dawley rats) at both 6 and 18 days of age. At 18 days of age, they also show a preference for dilute NaCl over water in a simultaneous choice paradigm. In contrast, only 1-3 days later when these animals are weaned, they strongly reject NaCl solutions from sipper tubes in favor of water. It is unlikely that an abrupt discontinuity in neurosensory development can fully explain this dramatic reversal in salt acceptance. PMID- 1936584 TI - Insulin, prostaglandins, and the pathogenesis of hypertension. AB - Hypertension is associated with hyperinsulinemia in the presence or absence of obesity or glucose intolerance. Physiological concentrations of insulin decrease the catecholamine-induced production of prostaglandin I2 (PGI2; prostacyclin) and PGE2, two potent vasodilators, in adipose tissue, one of the largest organs in the body. This finding suggests that hyperinsulinemia increases peripheral vascular resistance and blood pressure by inhibiting the stimulatory effect of adrenergic agonists (and perhaps other agonists) on the production of PGI2 and PGE2 in adipose tissue (and perhaps other tissues). This concept is supported by evidence that PGI2 and PGE2 modulate vascular reactivity in states of health and disease. For example, during insulin deficiency, i.e., in diabetic ketoacidosis, PGI2 and PGE2 production by adipose tissue are increased, and peripheral vascular resistance and blood pressure are decreased. This hypothesis is also supported by evidence that blood flow through rat and human adipose tissue is decreased in obesity and that insulin decreases the blood flow through adipose tissue in nonobese rats. Thus, insulin may regulate PGI2 and PGE2 production by adipose tissue (and possibly other tissues) through a wide range of concentrations with important physiological and clinical consequences. PMID- 1936585 TI - Stimulation of lipolysis in humans by physiological hypercortisolemia. AB - The effect of glucocorticoids on adipose tissue lipolysis in animals and humans is controversial. To determine whether a physiological increase in plasma cortisol, similar to that observed in diabetic ketoacidosis and other stress conditions, stimulates lipolysis, palmitate kinetics were measured in seven nondiabetic volunteers on two occasions with [1-14C]palmitate as a tracer. Subjects received a 6-h infusion of either 2 micrograms.kg-1.min-1 hydrocortisone or saline in random order. On both occasions, a pancreatic clamp (0.12 micrograms.kg-1.min-1 somatostatin, 0.05 mU.kg-1.min-1 insulin, and 3 ng.kg-1.min 1 growth hormone) was used to maintain plasma hormone concentrations at desired levels. Plasma cortisol concentrations increased to approximately 970 nM during cortisol infusion. Palmitate rate of appearance (Ra) and concentration increased by approximately 60% during cortisol infusion but did not change during saline infusion. Increments in palmitate Ra and concentration over the 6-h study were significantly greater during cortisol than saline infusion when compared by area under-the-curve analysis (152 +/- 52 vs. -48 +/- 23 mumol.kg-1 and 12.2 +/- 4.1 vs. -4.9 +/- 4.1 mmol.min-1.L-1, respectively; P less than 0.02). Plasma glucose concentrations did not change significantly during cortisol (5.0 +/- 0.3 vs. 6.1 +/- 0.6 mM, NS) or saline (4.9 +/- 0.2 vs. 4.9 +/- 0.1 mM, NS) infusion. In nondiabetic volunteers, a 6-h cortisol infusion was associated with a 60% increase in palmitate Ra that did not occur with saline infusion. Thus, physiological hypercortisolemia may contribute to the increased rates of lipolysis observed in humans during stress. PMID- 1936586 TI - Crucial role of aldose reductase activity and plasma glucose level in sorbitol accumulation in erythrocytes from diabetic patients. AB - Increased sorbitol levels have been demonstrated in tissues of diabetic patients. Although tissue sorbitol levels correlate with plasma glucose levels, a large variability in sorbitol levels has been observed among diabetic patients with similar plasma glucose levels. This variability in tissue sorbitol levels may be due to differences in the activity of aldose reductase, the enzyme that converts glucose to sorbitol. In this study, we isolated aldose reductase from erythrocytes of 31 diabetic patients and 6 nondiabetic control subjects, measured its activity, and compared it to simultaneously measured erythrocyte sorbitol levels. The activity of erythrocyte aldose reductase was increased in diabetic patients compared with control subjects (28.1 +/- 1.4 vs. 22.4 +/- 1.7 nmol.min 1.g-1 Hb, P less than 0.05), but there was an approximately threefold variation in aldose reductase activity among diabetic patients. Erythrocyte aldose reductase activity and fasting plasma glucose levels significantly correlated with the erythrocyte sorbitol level in all individuals (r = 0.48, P less than 0.005 and r = 0.63, P less than 0.005, respectively). The sorbitol level was higher in patients with high aldose reductase activity than in those who had low enzyme activity for any given level of glycemia. The sorbitol production rate calculated from Km and Vmax values showed a better correlation with the erythrocyte sorbitol level (r = 0.80, P less than 0.005), and there was also a good correlation between the erythrocyte sorbitol level and the product of aldose reductase activity by plasma glucose level (r = 0.70, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936587 TI - Reduced vitamin E and increased lipofuscin products in erythrocytes of diabetic rats. AB - Vitamin E deficiency in erythrocytes causes decreased cell survival, hypercoagulability, and increased adhesiveness to the endothelium. Similar abnormalities are found in erythrocytes of the diabetic population. This study examines the effect of diabetes on vitamin E and lipofuscin products (aging pigments) in erythrocytes of streptozocin-induced diabetic rats. Controls were injected with buffer alone, and a subgroup consisting of insulin-treated diabetic rats were injected daily with insulin for 2 mo. Mean +/- SD vitamin E levels were 23.2 +/- 4.9, 19.4 +/- 3.2, and 25.9 +/- 2.5 nmol/mumol phospholipid. Lipid fluorescence values (relative values/phospholipid) were 11.1 +/- 1.9, 14.1 +/- 2.6, and 11.9 +/- 1.8 (excitation/emission 360/440 nm) in control, diabetic, and insulin-treated diabetic rats, respectively. Differences in vitamin E and lipofuscin products were significant between all control and diabetic groups and diabetic and insulin-treated diabetic groups. Reduction in vitamin E and increases in lipofuscin products in diabetic rats were significant even when values were expressed per micromole Hb or per 100 ml erythrocytes. This study demonstrates that hyperglycemia significantly reduces vitamin E and increases lipofuscin products in erythrocytes of diabetic rats. These effects were prevented with insulin treatment. PMID- 1936588 TI - Diabetic environment and genetic predisposition as causes of congenital malformations in NOD mouse embryos. AB - Congenital malformations such as neural tube defects and a kinky or waved vertebral column were observed at higher incidence in embryos from nonobese diabetic (NOD) female mice with overt diabetes (NOD-D; 40.3%, P less than 0.005) or without overt diabetes (NOD-N; 8.4%, P less than 0.05) than in control Institute of Cancer Research (ICR) mouse embryos (1%) at day 13 of gestation. In vivo and in vitro preimplantation development of NOD-N, NOD-D, and ICR embryos did not differ in rate of development, size, or morphology. Embryos cultured from one-cell to early blastocyst stage were mutually transferred to uterine horns of pseudopregnant females between NOD-D and ICR mice and examined at day 13 of gestation. There were significant decreases in ratios of implantation and of viable embryos in ICR embryos transferred to NOD-D recipients (52%, P less than 0.001 and 14%, P less than 0.001, respectively) compared with those ratios in ICR embryos transferred to ICR uteri (79.2 and 56.2%) or those in NOD-D embryos transferred to ICR uteri (70.3 and 33.1%). Furthermore, 18 of 45 viable ICR embryos transferred to NOD-D dams had malformations, whereas there were no malformations in 73 viable ICR embryos transferred to ICR recipients, suggesting deleterious effects of maternal diabetic environment to embryos. On the other hand, 8 of 58 viable NOD-D embryos that were cultured in vitro and transferred to ICR uteri had malformations such as neural tube defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936589 TI - Direct vital microscopic study of defective leukocyte-endothelial interaction in diabetes mellitus. AB - The number of leukocytes rolling along the venular endothelium of the vascular network of the internal spermatic fascia was determined in nondiabetic control rats and diabetic rats with television microscopy. A marked decrease in the number of rolling cells was observed in animals rendered diabetic by the injection of alloxan 10, 30, or 180 days before relative to matching controls. Blood leukocyte counts, however, were equivalent in both control and diabetic rats. Under the influence of a local inflammatory stimulus, cells emerged into the perivascular tissue in control animals, and this was accompanied by a reduction in the number of rolling leukocytes. In diabetic rats, the number of rolling leukocytes remained unaltered, and only a few cells accumulated in the connective tissue adjacent to the vessel. Reversal of the defective leukocyte endothelial interaction was attained by treatment of diabetic animals with insulin. Inhibitors of arachidonic acid metabolism were ineffective to improve leukocyte-endothelial interactions in diabetic animals. Control rats injected intravenously with lyophilized plasma constituents, obtained after dialysis of diabetic rat plasma with 12,000-Mr retention dialysis tubing, behaved as diabetic animals in that they exhibited a reduced number of leukocytes rolling along the venular endothelium. In contrast, material obtained from control rat plasma produced no effect. Heating of active samples for 1 h at 56 degrees C resulted in the complete loss of the inhibitory effect. We conclude that a substance or substances present in diabetic plasma induce a defective leukocyte-endothelial interaction that further impairs resistance to infection. PMID- 1936590 TI - Downregulation of protein kinase C and insulin-stimulated 2-deoxyglucose uptake in rat adipocytes by phorbol esters, glucose, and insulin. AB - Phorbol esters translocatively activate and subsequently downregulate protein kinase C and insulin-stimulated glucose uptake in rat adipocytes. This study examined the possibility that other translocative activators of protein kinase C in rat adipocytes, e.g., insulin and glucose, provoke similar downregulating effects. Pretreatment of rat adipocytes for 20-24 h with phorbol esters, 3 nM insulin, 20 mM glucose, or 3 nM insulin plus 20 mM glucose resulted in concomitant decreases in protein kinase C and insulin-stimulated (or phorbol ester-stimulated) [3H]-2-deoxyglucose uptake. Downregulating effects of glucose on protein kinase C and insulin-stimulated [3H]-2-deoxyglucose uptake were also evident within 30 min in adipocytes freshly incubated in medium containing 5-20 mM, rather than 0, glucose. These findings confirm that protein kinase C is required during insulin-stimulated glucose uptake and raise the possibility that downregulation of protein kinase C by continued translocative activation of the enzyme may contribute (along with other factors) to impaired responsiveness of the glucose transport system after prolonged insulin and/or glucose treatment. PMID- 1936591 TI - Alteration of cholecystokinin-mediated phosphatidylinositol hydrolysis in pancreatic acini from insulin-deficient rats. Evidence for defective G protein activation. AB - Insulin deficiency leads to a decreased ability of cholecystokinin octapeptide (CCK-8) to raise cytosolic free-calcium levels in the pancreatic acinar cell. To elucidate the mechanisms underlying this defect, we studied the effects of CCK-8 on phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis in pancreatic acini prepared from nondiabetic and streptozocin-induced diabetic rats. Analysis by high-pressure liquid chromatography indicated that, in diabetic rat acini, the CCK-8-mediated increase in [3H]inositol 1,4,5-trisphosphate ([3H]IP3) levels was delayed, and the increase in [3H]inositol 1,3,4,5-tetrakisphosphate ([3H]IP4) levels was markedly attenuated compared with nondiabetic rat acini. The expected increase in the mass levels of IP3, measured in a competitive binding assay, was reduced in the diabetic group after incubation with CCK-8, carbachol, and bombesin. Phospholipase C activity was decreased by 30% in diabetic rat acini, whereas the specific activity of PIP2 and the amount of myo-[3H]inositol in the free and trichloroacetic acid-precipitable pools were similar in both groups. The nonhydrolyzable analogue of GTP guanosine-5'-O-(3'-thiotriphosphate) rapidly enhanced IP3 levels in permeabilized acini, and the percent increase above basal was greater in the diabetic group. When added for 5 s or 2 h, insulin did not alter basal or CCK-8-stimulated [3H]IP3 and [3H]IP4 levels in either nondiabetic or diabetic rat acini. However, after a 4-h incubation, insulin increased basal [3H]IP3 and [3H]IP4 levels in diabetic rat acini and potentiated the actions of CCK-8 on both inositol phosphates. Insulinlike growth factor I did not alter [3H]IP3 and [3H]IP4 levels either acutely or after a 4-h incubation. These findings point to a defect in the signal-transduction pathway that is activated by CCK-8 and other calcium-mobilizing agonists in the diabetic rat pancreas and suggest that insulin, acting via its own receptor, exerts long-term regulatory effects on PIP2 hydrolysis in the pancreatic acinar cell. PMID- 1936592 TI - Differential regulation of glycosylated phosphatidylinositol subtypes by insulin. AB - Glycosylated phosphatidylinositol (gly-Pl) molecules have been implicated as precursors for insulin-sensitive second messengers (1-4) and lipid-anchored membrane proteins (5-9). The relationship between the diverse functions of these lipids and their predicted structural heterogeneity within gly-Pl subtypes was examined in human T lymphocytes. Four subtypes of gly-Pl molecules were identified in T lymphocytes after separation over high-performance thin-layer chromatography by sensitivity to Pl-specific phospholipase C and nitrous acid. Antibody probes of the glycan domain of gly-Pl were developed and used to assess the partial sensitivity of gly-Pl to insulin action. This analysis showed that the effects of insulin are linked to differential utilization of only two of the four gly-Pl subtypes in T lymphocytes. Polar fragments of this reaction were identified in extracellular supernatants from insulin-treated cells. The biological significance of insulin-dependent gly-Pl hydrolysis was demonstrated by insulin and inositol phosphoglycan regulation of glucose metabolism in intact lymphocytes. These results support the hypothesis that multifunctional roles of gly-Pl are served by discrete gly-Pl populations and that metabolites of gly-Pl subsets participate as signaling elements in insulin action. PMID- 1936593 TI - Chronology and determinants of tissue repair in diabetic lower-extremity ulcers. AB - The natural history of tissue repair and the critical determinants of faulty healing of diabetic ulcers remain obscure despite recent advances in our knowledge of the cellular physiology of normal cutaneous healing. To characterize the chronology and identify important factors affecting healing, we applied an objective method to quantify the rate of wound healing of full-thickness lower extremity ulcers in 46 diabetic outpatients who received local wound care under a standardized clinical protocol. The initial ulcer healing rate, eventual status of tissue repair, and definitive clinical outcome were not significantly associated with age; diabetes type, duration, or treatment; level or change in glycosylated hemoglobin; current smoking; presence of sensory neuropathy; ulcer location or class; initial infection; or frequency of recurrent infections. However, direct measures of local cutaneous perfusion, estimated by periwound measurements of transcutaneous O2 tension (TcPo2) and transcutaneous CO2 tension (TcPco2), were significantly associated with the initial rate of tissue repair (P = 0.003 and 0.005, respectively). The strong prediction of early healing by these parameters of local skin perfusion was independent from the effects of segmental Doppler arterial blood pressure at the dorsalis pedis, although eventual ulcer reepithelialization was significantly related to foot blood pressure and periwound TcPo2 and TcPco2. We conclude that periwound cutaneous perfusion is the critical physiological determinant of diabetic ulcer healing, indicating a 39 fold increased risk of early healing failure when the average periwound TcPo2 is less than 20 mmHg. PMID- 1936594 TI - No reduction in total hepatic glucose output by inhibition of gluconeogenesis with ethanol in NIDDM patients. AB - Increased gluconeogenesis has been suggested to account for all of the increase in basal glucose production in patients with non-insulin-dependent diabetes mellitus (NIDDM). We studied the effect of inhibition of gluconeogenesis with ethanol on total hepatic glucose output (HGO) in patients with NIDDM. Fourteen patients with NIDDM (mean +/- SE age 61 +/- 2 yr, fasting plasma glucose 11.4 +/- 0.8 mM; body mass index 27 +/- 1 kg/m2) were studied twice after an overnight fast, once during ethanol administration (blood ethanol approximately 12 mM) and once during saline administration. Total HGO rate was measured with [3H]glucose. Inhibition of gluconeogenesis by ethanol was followed qualitatively with [U 14C]lactate (n = 8) and [U-14C]glycerol (n = 6) as tracers. Ethanol inhibited gluconeogenesis from lactate by 71 +/- 5% (0.5 +/- 0.2 vs. 1.8 +/- 0.1 mumol glucose.kg-1.min-1, 240-300 min, P less than 0.001; ethanol vs. saline, P less than 0.001) and from glycerol by 65 +/- 6% (0.8 +/- 0.2 vs. 2.3 +/- 0.6 mumol glucose.kg.min-1, P less than 0.001). Total HGO rate remained unchanged and averaged 12.8 +/- 1.8 and 11.8 +/- 2.1 mumol.kg-1.min-1 in the saline and ethanol studies, respectively (NS). We concluded that inhibition of gluconeogenesis by ethanol does not decrease total HGO in patients with NIDDM. Our results suggest the existence of a regulatory mechanism in the liver that maintains constant total HGO despite inhibition of gluconeogenesis. PMID- 1936595 TI - Sorbitol, myo-inositol, and rod outer segment phagocytosis in cultured hRPE cells exposed to glucose. In vitro model of myo-inositol depletion hypothesis of diabetic complications. AB - The "myo-inositol depletion hypothesis" remains a leading but still controversial contender among proposed pathogenetic mechanisms for the chronic complications of diabetes. The multifaceted interrelationships among altered tissue myo-inositol content and metabolism and tissue function have been difficult to elucidate in diabetic animal models due in part to the complex, heterogeneous nature of tissues prone to diabetic complications. The retinal pigment epithelium consists of a homogenous cell monolayer that exhibits related alterations in myo-inositol metabolism and function in diabetic animals. Nontransformed human retinal pigment epithelial (hRPE) cells, which retain their general phenotypic and morphological characteristics during monolayer culture in vitro, were examined for parallel alterations in myoinositol metabolism and cell function when grown under carefully controlled conditions in medium containing hyperglycemic concentrations of glucose. Exposure of hRPE cells to 20-40 mM glucose produced time- and dose dependent increases in sorbitol content and decreases in myo-inositol content that were partially blocked by the aldose reductase inhibitor sorbinil. myo Inositol was taken up by two Na-dependent transport systems, at least one of which was competitively inhibited by glucose. Exposure to 20 mM glucose impaired the ability of hRPE cells to take up human retinal rod outer segments, an important physiological function of these cells. The impairment of rod outer segment uptake by high glucose levels was prevented by an aldose reductase inhibitor or elevated medium myo-inositol that corrected the fall in myo-inositol content. Thus, hRPE cells provide a new in vitro model in which to examine the biochemical-functional interrelationships of the myo-inositol depletion hypothesis. PMID- 1936596 TI - Effects of IGF-I and glucose on protein and proteoglycan synthesis by human fetal mesangial cells in culture. AB - Abnormalities in proteoglycan metabolism have been implicated in the pathogenesis of diabetic nephropathy. Whether hyperglycemia plays a direct role in these events is unknown. To evaluate the effects of high glucose concentrations and insulinlike growth factor I (IGF-I) on kidney proteoglycan and protein metabolism, we incubated quiescent, subconfluent human fetal mesangial cells for 24 h in serum-free media containing either physiological (5.6-mM) or elevated (25 mM) glucose concentrations with or without 1.3 x 10(-9) M IGF-I. In the presence of physiological glucose concentrations, IGF-I stimulated incorporation of [3H]leucine into protein and [35S]sulfate or [3H]glucosamine into proteoglycans. High glucose concentrations significantly amplified IGF-I-mediated stimulation of protein synthesis but totally abolished IGF-I-induced proteoglycan synthesis. The hydrodynamic size and proportions of heparan-35SO4 and chondroitin/dermatan-35SO4 proteoglycans in all experimental media were the same. However, high glucose concentrations decreased the iduronic acid content of dermatan-35SO4. In separate experiments, quiescent cells were cultured for 7 days in media supplemented with 2% fetal calf serum. IGF-I had no effect on mesangial cell proliferation, but as cells reached confluence, high glucose concentrations significantly inhibited cell proliferation. This inhibition was not mimicked by isosmolar concentrations of mannitol. After 7 days, uptake of radioactive precursors into proteoglycans and proteins over 24 h was similar under all culture conditions. However, IGF-I decreased the ratio of [35S]sulfate to [3H]glucosamine in proteoglycans and their glycosaminoglycan side chains. This difference persisted in disaccharides derived by chondroitin ABC lyase digestion of dermatan-35SO4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936597 TI - Activation by vanadate of glycolysis in hepatocytes from diabetic rats. AB - In hepatocytes from starved streptozocin-induced diabetic rats, vanadate increases the glycolytic flux because it raises the levels of fructose-2,6 bisphosphate (Fru-2,6-P2), the main regulatory metabolite of this pathway. This effect of vanadate on Fru-2,6-P2 levels is time and dose dependent, and it remains in cells incubated in a calcium-depleted medium. Vanadate is also able to counteract the decrease on Fru-2,6-P2 levels produced by glucagon, colforsin, or exogenous cAMP. However, vanadate does not modify 6-phosphofructo-2-kinase and pyruvate kinase activities, but it does counteract the inactivation of these enzymes induced by glucagon. Likewise, Fru-2,6-P2ase activity is also not affected by vanadate. In addition, vanadate is able to increase the production of both lactate and CO2 in hepatocytes from streptozocin-induced diabetic rats incubated in the presence of glucose in the medium. Vanadate behaves as a glycolytic effector in these cells, and this effect may be related to its ability to normalize blood glucose levels in diabetic animals. PMID- 1936598 TI - Synergism of obesity genes with hepatic steroid sulfotransferases to mediate diabetes in mice. AB - Sulfotransferases controlling the intrahepatic ratio of active androgens to estrogens represent key determinants of whether an obesity mutation will be diabetogenic in C57BL/KsJ female mice. Three unlinked genes (diabetes [db], obese [ob], and fat [fat]) all produced comparable obesity in C57BL/KsJ females, but only the fat mutation was not diabetogenic. The fat gene was incapable of eliciting virilizing changes in hepatic sulfotransferase activity, whereas both db and ob accelerated estrogen and suppressed androgen sulfation. Northern-blot analysis confirmed anomalous suppression of hepatic androgen sulfotransferase transcription in db and ob but not fat females. These findings suggest the utility of obesity genes in analyzing the interaction between hyperandrogenism, hyperinsulinemia, and diabetes. PMID- 1936599 TI - Structural and functional considerations of GABA in islets of Langerhans. Beta cells and nerves. AB - gamma-Aminobutyric acid (GABA), a prominent inhibitory neurotransmitter, is present in high concentrations in beta-cells of islets of Langerhans. The GABA shunt enzymes, glutamate decarboxylase (GAD) and GABA transaminase (GABA-T), have also been localized in islet beta-cells. With the recent demonstration that the 64,000-M, antigen associated with insulin-dependent diabetes mellitus is GAD, there is increased interest in understanding the role of GABA in islet function. Only a small component of beta-cell GABA is contained in insulin secretory granules, making it unlikely that GABA, coreleased with insulin, is physiologically significant. Our immunohistochemical study of GABA in beta-cells of intact islets indicates that GABA is associated with a vesicular compartment distinctly different from insulin secretory granules. Whether this compartment represents a releasable pool of GABA has yet to be determined. GAD in beta-cells is associated with a vesicular compartment, similar to the GABA vesicles. In addition, GAD is found in a unique extensive tubular cisternal complex (GAD complex). It is likely that the GABA-GAD vesicles are derived from this GAD containing complex. Physiological studies on the effect of extracellular GABA on islet hormonal secretion have had variable results. Effects of GABA on insulin, glucagon, and somatostatin secretion have been proposed. The most compelling evidence for GABA regulation of islet hormone secretion comes from studies on somatostatin secretion, where it has an inhibitory effect. We present new evidence demonstrating the presence of GABAergic nerve cell bodies at the periphery of islets with numerous GABA-containing processes extending into the islet mantle. This close association between GABAergic neurons and islet alpha- and delta-cells strongly suggests that GABA inhibition of somatostatin and glucagon secretion is mediated by these neurons. Intracellular beta-cell GABAA and its metabolism may have a role in beta-cell function. New evidence indicates that GABA shunt activity is involved in regulation of insulin secretion. In addition, GABA or its metabolites may regulate proinsulin synthesis. These new observations provide insight into the complex nature of GABAergic neurons and beta-cell GABA in regulation of islet function. PMID- 1936600 TI - Effect of insulin and statil on aldose reductase expression in diabetic rats. AB - Tissue accumulation of sorbitol secondary to enhanced polyol-pathway activity is believed to play an important role in the development of diabetic complications. We previously demonstrated sorbitol accumulation, due in part to enhanced expression of aldose reductase (AR) in the diabetic kidney. In this study, we quantitated AR enzyme activity, immunoreactivity, and mRNA in various tissues from nondiabetic and diabetic BB/Wor rats 3 mo after onset of diabetes. In addition, the effects of intensive insulin treatment (3-6 U/day) and the effects of the AR inhibitor Statil (25 mg.kg-1.day-1) on AR expression were determined. Of 13 tissues examined, AR activity was significantly increased in the lens, kidney, sciatic nerve, skeletal muscle, retina, and spinal cord from diabetic rats compared with age-matched nondiabetic control rats. In most tissues, AR immunoreactivity and AR mRNA were proportionately elevated. Intensive insulin treatment, which normalized blood glucose and glycosylated hemoglobin, significantly reduced AR activity and immunoreactivity. AR mRNA abundance was also reduced in tissues from insulin-treated diabetic rats. Statil treatment had no significant effect on AR immunoreactivity or AR mRNA abundance, although AR activity in tissues from Statil-treated diabetic rats was significantly reduced compared with untreated diabetic rats. These studies demonstrate that the expression of the AR gene is upregulated in most tissues of the diabetic rat, that insulin treatment reverses this phenomenon, and that AR inhibition has no effect on AR gene expression. PMID- 1936601 TI - Development of muscle insulin resistance after liver insulin resistance in high fat-fed rats. AB - Muscle and hepatic insulin resistance are two major defects of non-insulin dependent diabetes mellitus. Dietary factors may be important in the etiology of insulin resistance. We studied progressive changes in the development of high-fat diet-induced insulin resistance in tissues of the adult male Wistar rat. In vivo insulin action was compared 3 days and 3 wk after isocaloric synthetic high-fat or high-starch feeding (59 and 10% cal as fat, respectively). Basal and insulin stimulated glucose metabolism were assessed in the conscious 5- to 7-h fasted state with the euglycemic clamp (600 pM insulin) with a [3-3H]-glucose infusion. Fat feeding significantly reduced suppressibility of hepatic glucose output by insulin after both 3 days and 3 wk of diet (P less than 0.01). However, a significant impairment of insulin-mediated peripheral glucose disposal was only present after 3 wk of diet. Further in vivo [3H]-2-deoxyglucose uptake studies supported this finding and demonstrated adipose but not muscle insulin resistance after 3 days of high-fat feeding. Muscle triglyceride accumulation due to fat feeding was not significant at 3 days but had doubled by 3 wk in red muscle (P less than 0.001) compared with starch-fed controls. By 3 wk, high-fat-fed animals had developed significant glucose intolerance. We conclude that fat feeding induces insulin resistance in liver and adipose tissue before skeletal muscle with early metabolic changes favoring an oversupply of energy substrate to skeletal muscle relative to metabolic needs. This may generate later muscle insulin resistance. PMID- 1936602 TI - Platelet adhesion and aggregate formation in type I diabetes under flow conditions. AB - To study platelet activation as a phenomenon that may precede development of angiopathy in diabetes mellitus, we compared platelet adhesion and thrombus formation in a flow system with blood from insulin-dependent (type I) diabetic subjects with and without macroangiopathy and age- and sex-matched control subjects. Adhesion and thrombus formation on matrix of cultured human endothelial cells (ECM) and adhesion on matrix of human fibroblasts (FBM) were studied after exposure to flowing blood at shear rates of 300 and 1300 s-1 and exposure times of 1, 3, 5, and 10 min (and 20 min in adhesion experiments). Blood was anticoagulated with trisodium citrate (1:10 vol/vol, 110 mM) or low-molecular weight heparin ([LMWH] 20 U/ml). Endothelial cell cultures were either unstimulated or stimulated with 4 beta-phorbol 12-myristate 13-acetate (PMA) 16 h before isolating their matrix. Platelet adhesion on ECM and FBM in citrated and LMWH-anticoagulated blood was identical in diabetic patients and control subjects, with comparable increases of adhesion with increasing perfusion times. Platelet aggregate formation on ECM of PMA-stimulated cells with LMWH anticoagulated blood was similar in diabetic patients, whether macroangiopathy was present, compared with control subjects. Fibrin deposition and fibrinopeptide A generation during perfusion were comparable in diabetic and control subjects. Platelet thromboxane B2 formation after stimulation with arachidonic acid was increased in diabetic patients without macroangiopathy compared with age- and sex matched control subjects. In the perfusion system, the patterns of platelet adhesion and aggregate formation on extracellular matrix in flowing blood of diabetic patients (with or without macroangiopathy), and healthy age- and sex matched control subjects followed a similar pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936603 TI - Liposomal delivery of purified heat shock protein hsp70 into rat pancreatic islets as protection against interleukin 1 beta-induced impaired beta-cell function. AB - Recently it has been demonstrated that heat shock protein 70 (hsp70) is induced in pancreatic islet cells during prolonged exposure to interleukin 1 beta (IL-1 beta). It is unclear whether this represents a cellular defense against the noxious action of IL-1 beta or whether hsp70 is involved in the suppressive action of the cytokine. To assess the role for hsp70 in isolated islets exposed to IL-1 beta, hsp70 was purified and introduced into cells of isolated rat pancreatic islets via the liposome technique. Delivery of hsp70 was efficient according to immunoblot analysis, but delivered hsp70 disappeared within 16 h. Hsp70-containing liposomes did not affect protein synthesis, insulin secretion, or islet insulin mRNA content. However, when hsp70 liposome-incubated islets were further exposed to IL-1 beta (25 U/ml) for 16 h, these islets released more insulin in response to glucose stimulation and contained more insulin mRNA than islets incubated with control liposomes and subsequently exposed to the cytokine. No protective effect of liposomes containing bovine serum albumin or ovalbumin were observed. We conclude that hsp70 may protect against IL-1 beta-induced impairment of pancreatic beta-cell function. PMID- 1936604 TI - Epidemiology and immunogenetic background of islet cell antibody--positive nondiabetic schoolchildren. Ulm-Frankfurt population study. AB - Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes. PMID- 1936605 TI - Sustained pulsatile insulin secretion from adenomatous human beta-cells. Synchronous cycling of insulin, C-peptide, and proinsulin. AB - The endocrine pancreas secretes insulin in a pulsatile fashion. This rhythm is generated at a site within the pancreas, although its precise location has not been determined. With an in vitro system, we tested the possibility that beta cells might generate spontaneous pulsatile insulin secretion in the absence of any external influence. Human insulinoma tissue from five patients was perifused for 7-10 h with RPMI-1640 medium and constant concentrations of glucose (5.5 mM). Insulin, C-peptide, and proinsulin were measured in the effluent collected at 3.3 min intervals. All three peptides demonstrated pulsatility of secretion in a similar, synchronous fashion that was sustained throughout each study. The Clifton cycle detection program demonstrated cycling in all five tumors, with an average period for all tumors of 28, 29, and 26 min for insulin, C-peptide, and proinsulin, respectively. Spectral analysis confirmed the regularity and consistency of the hormonal secretory patterns. Mean hormone concentrations secreted by different tumors varied, but insulin and C-peptide were secreted in a nearly 1:1 ratio. This study demonstrates 1) that beta-cells are able to generate spontaneous pulsatile insulin secretory activity, which is independent of innervation or the presence of other islet cells, and 2) proinsulin secretion from the beta-cell also has an inherent pulsatility. The synchrony observed in the cycles of proinsulin and its peptide products confirms their common secretory pathway in the beta-cell. We conclude that the beta-cell may be the originator of insulin cycling. PMID- 1936606 TI - Deterioration of islet beta-cell function after hemipancreatectomy in dogs. AB - The metabolic consequences of hemipancreatectomy in living pancreas donors were tested in a dog model in which a 50% lobe-specific pancreatectomy was performed. Removal of the dorsal lobe (analogous to a donor, n = 4) resulted in a progressive increase in fasting glucose during 12 mo from 5.32 +/- 0.16 to 8.17 +/- 0.28 mM and a decrease in fasting insulin from 54 +/- 3 to 6.0 +/- 2.4 pM and glucose clearance (Kg) from 3.00 +/- 0.22 to 1.00 +/- 0.06 mM. Removal of the ventral lobe (analogous to a recipient, n = 5) did not result in a change in fasting glucose or Kg during 12 mo, although fasting insulin was reduced from 36.0 +/- 1.8 to 18.00 +/- 1.93 pM. In vitro perfusion of the remnants after 1 yr showed a deterioration in glucose-stimulated insulin secretion (5-11 mM) by the dorsal remnant (18 +/- 11 vs., 232 +/- 37%) and the ventral remnant (2.6 +/- 19 vs. 87 +/- 13%). The dorsal remnant had a higher response than the ventral remnant (46 +/- 23 vs. -16 +/- 10%, respectively) to severe hyperglucosuria (11 27.7 mM). Insulin content was unchanged in the dorsal remnant (224 +/- 16 vs. 180 +/- 14 micrograms/g), but was reduced in the ventral remnant (65 +/- 14 vs. 154 +/- 15 micrograms/g). In vitro insulin pulse intervals were reduced in both remnants (5.3 +/- 0.2 min vs. control 7.00 +/- 0.18 min). Because of the above effects on the donor when the dorsal lobe is removed, the continued use of hemipancreatectomy as a source of transplantable tissue must be questioned. PMID- 1936607 TI - Evolution of insulin resistance in New Zealand obese mice. AB - The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is not known. Hyperglycemia is due to increased hepatic glucose production (HGP), decreased glucose uptake, and impaired insulin secretion. It is unknown if these defects are coinherited or if one precedes and causes the others. The aim of this study was to determine the earliest defects in the evolution of the syndrome in the New Zealand obese (NZO) mouse, a polygenic model of NIDDM. NZO and control NZC mice were studied at 4-5 and 20 wk of age. Glucose turnover and glucose uptake in individual tissues were measured basally and during a hyperinsulinemic clamp. First-phase insulin secretion was measured after an intravenous glucose load. HGP was higher in the NZO mice both basally and during the clamp at both ages. At 4-5 wk of age, there was evidence of insulin insensitivity in brown adipose tissue, soleus, diaphragm, red quadriceps, and red gastrocnemius but not in heart, white quadriceps, and white gastrocnemius. In 20-wk-old mice, insulin responsiveness was decreased in white and brown adipose tissue and soleus muscle but not in heart, diaphragm, red and white quadriceps, and red and white gastrocnemius. First-phase insulin secretion (percentage rise above basal) 3 min after the glucose bolus was impaired in NZO mice at both ages. We conclude that hepatic glucose overproduction, brown adipose tissue and skeletal muscle insulin resistance, and impaired first-phase insulin secretion are all early abnormalities in the NZO mouse. PMID- 1936608 TI - Age-dependent expression of protein kinase C isoforms in rat islets. AB - The appearance of the biphasic insulin secretory response several days after birth suggests that maturation of a critical step in stimulus-secretion coupling occurs during the early neonatal period. To clarify the role of protein kinase C (PKC) during this time, we examined the pancreatic islets of adult, 3-day neonatal, and 19-day fetal rats for the presence of different PKC isoenzymes. Western-blot analysis of islet extracts showed the presence of PKC isoforms in both adult and neonatal tissues. Immunocytochemistry of adult islets revealed a differential expression in islet cell types. PKC-alpha was found only in beta cells, PKC-gamma in alpha-cells, and PKC-epsilon in delta-cells and vascular walls. Immunoreactivity for PKC-beta was not detected in any cell type. All three isoenzymes were also present in neonatal islets; however, in contrast to adult tissue, immunoreactivity for either PKC-alpha or PKC-gamma was present in relatively few cells. There was no apparent immunoreactivity for PKC-alpha or PKC gamma in fetal islets, although these tissues contained strong staining for insulin and glucagon. These data show that three of the PKC isoforms are restricted to a particular islet cell type, where they may play a unique role in the secretion of a specific hormone. Moreover, our results demonstrate that these enzymes, especially PKC-alpha, appear during the early neonatal period. This age dependent expression may be linked to the development of the biphasic insulin release response. PMID- 1936609 TI - Prolonged reversal of diabetic state in NOD mice by xenografts of microencapsulated rat islets. AB - Transplantation of the islets of Langerhans could be the most promising approach to the clinical treatment of insulin-dependent (type I) diabetes mellitus. In this study, we report on a modified encapsulation technique that produces small alginate-polylysine capsules (0.25-0.35 mm diam). In an in vitro study, both encapsulated and unencapsulated islets showed comparable responses to glucose challenge in terms of insulin secretion. With the new capsules, 16 spontaneously diabetic NOD mice received transplants of 800 encapsulated rat islets/animal. Nonfasting blood glucose concentration decreased from 24.4 +/- 1.4 to 4.0 +/- 1.3 mM. At 4 and 5 mo posttransplantation, the capsules were removed from 2 recipients. Both animals regressed to a hyperglycemic state after capsule removal. However, after another islet transplantation, normoglycemia was again restored in these 2 animals. In control mice, which received unencapsulated islets, the xenografts remained functional for less than 10 days. A high mortality rate was observed among these animals within 2 mo of the recurrence of the hyperglycemic state. Our results clearly indicate that encapsulation of pancreatic islets in the improved capsules can effectively prolong xenograft survival without immunosuppression in an animal model that mimics human type I diabetes mellitus. PMID- 1936610 TI - Nutrition and somatomedin. XXVI. Molecular regulation of IGF-I by insulin in cultured rat hepatocytes. AB - Although decreased levels of circulating insulinlike growth factor I (IGF-I) and hepatic IGF-I mRNA in diabetic animal models support a role for insulin in IGF-I regulation, it has been difficult to study the effects of insulin in vitro. Few immortal cell lines exhibit hormone-responsive production of IGF-I, and studies of cultured hepatocytes have often been inconclusive because conventional methods may not reproduce the IGF-I transcripts recognized in vivo. We have modified the hepatocyte isolation and RNA extraction procedures to circumvent this problem, resulting in transcripts of 1, 2, and 7.5 kb. With increasing insulin from 10( 10) to 10(-6) M, dexamethasone from 10(-10) to 10(-7) M, and amino acids from 1 to 10 x rat arterial levels, IGF-I release rose by 226, 257, and 447%, respectively (P less than 0.05), with correlated changes in IGF-I mRNA (r = 0.75, P less than 0.005). In the presence of 5 x amino acids and 10(-7) M dexamethasone, insulin-stimulated IGF-I release was dose dependent, increasing 183% at 10(-6) M (P less than 0.01). Across a broad range of amino acid concentrations (0.25-6.25 x), insulin provided consistent stimulation of both IGF I mRNA content and release of IGF-I. Cells cultured for 2 days at 10(-10) M insulin and then 2 days at 10(-6) M insulin released 66% more IGF-I than cells cultured 4 days at 10(-10) M insulin (P less than 0.01). Hepatocyte IGF-I release was correlated strongly with content of IGF-I mRNA, both sum of transcripts (r = 0.76, P less than 0.001) and individual transcripts. Insulin appears to regulate IGF-I release at the mRNA level in hepatocyte primary culture. This system should be a useful tool for further studies of molecular mechanisms of IGF-I regulation. PMID- 1936611 TI - Glyburide-stimulated glucose transport in cultured muscle cells via protein kinase C-mediated pathway requiring new protein synthesis. AB - To study the mechanism of action of sulfonylurea agents on peripheral tissues without the potentially confounding influences of insulin, the direct effect of glyburide (i.e., in the absence of insulin) was evaluated in the L6 cultured myogenic cell line. Glyburide approximately doubled the incorporation of [14C] glucose into glycogen. The rate-determining enzymes of glycogen metabolism, glycogen synthase and glycogen phosphorylase, were unaffected by the drug. Glucose transport (2-deoxyglucose uptake) was also approximately doubled. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) also doubled glucose transport and showed the same lag period (4-6 h) as glyburide before an effect occurred. Blockade of protein kinase C activity by either 1-(5 isoquinolinesulfonyl)-2 methyl piperazine (H7) or chronic exposure to TPA completely abolished the stimulation by glyburide. Cycloheximide, a protein synthesis inhibitor, also completely eliminated the effect of glyburide. The presence of ATP-sensitive K+ channels was assessed by measuring 86Rb efflux in ATP-depleted L6 muscle cells and RINm5F cells (which served as a positive control). Such channels were present and responded appropriately to glyburide and diazoxide in pancreatic beta-cells but were not present in muscle cells. Glyburide stimulation of glucose transport was completely eliminated by both Quin 2, an intracellular chelator of Ca2+, and verapamil, a Ca2+ channel blocker. However, glyburide did not raise intracellular Ca2+ levels. We conclude that glyburide stimulates glucose transport in cultured L6 muscle cells by a protein kinase C-mediated pathway that requires new protein synthesis. Although intracellular Ca2+ metabolism may also be involved, the initial step in the mechanism of action is probably different between pancreatic beta-cells and muscle cells. PMID- 1936612 TI - Signal peptide-length variation in human apolipoprotein B gene. Molecular characteristics and association with plasma glucose levels. AB - We studied the molecular characteristics of three naturally occurring variants in the human apolipoprotein B (apoB) signal peptide, their frequencies in non insulin-dependent diabetic and random populations, and their association with several measures of lipid and carbohydrate metabolism. In a random sample of 197 French whites, there were two common alleles, 5'beta SP-24 and 5'beta SP-27, with frequencies of 0.35 and 0.65, respectively. In a random sample of 181 Mexican Americans, there was an additional allele, 5'beta SP-29, with a frequency of 0.03. DNA sequence analysis indicated that the signal peptide alleles consisted of the following: 5'beta SP-29 encoded 29 amino acids in the signal peptide containing two copies of the sequence CTG GCG CTG encoding Leu-Ala-Leu and a consecutive run of eight Leu-encoding codons; 5'beta SP-27 encoded 27 amino acids with a run of only six Leu codons; 5'beta SP-24 encoded 24 amino acids and contained a single copy of CTG GCG CTG and a run of six Leu codons. In the sample of French whites, average apoAI and glucose levels were significantly different among signal peptide genotypes. 5'beta SP-24/24 homozygotes had higher apoAI levels than the two other signal peptide genotypes (1.59 vs. 1.42 g/L, respectively). Heterozygous 5'beta SP-24/27 individuals had the highest glucose levels. In the random sample of Mexican Americans, average glucose levels were also significantly different among signal peptide genotypes. However, the rank order of average glucose levels was not the same between the two samples.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936613 TI - Diabetes in NOD mice does not require T lymphocytes expressing V beta 8 or V beta 5. AB - The incidence of destructive pancreatic infiltrates and overt diabetes in animal models of insulin-dependent (type I) diabetes mellitus can be greatly reduced by inactivating or eliminating most T lymphocytes early in life. Because of theoretical and practical concerns about inducing long-term pan-T-lymphocyte inactivation for prevention or treatment of type I diabetes in humans, we hoped that more selective suppression of only the diabetogenic T lymphocyte population might be possible. To this end, two groups suggested that diabetogenic subpopulations of T lymphocytes in NOD mice could be identified by the protein sequence of their T-lymphocyte receptors. This assertion was based on experimental elimination of candidate T-lymphocyte subpopulations in two different short-term models of diabetes induction in NOD mice. For these experiments, identification and elimination of T-lymphocyte subsets were accomplished with monoclonal antibodies that bind specifically to the variable region of the beta-chain (V beta) of the T-lymphocyte antigen receptor and divide the T-lymphocyte pool of the NOD mouse into approximately 20 V beta subsets. To test the relationship between the two T-lymphocyte V beta subsets implicated in these studies and pancreatic beta-cell destruction in unmanipulated animals, both T-lymphocyte subpopulations identified were genetically eliminated from NOD derived mice by introduction of a mutant T-lymphocyte receptor V beta gene, from which these sequences are genomically deleted. Histological evidence of severe beta-cell destruction and overt diabetes was found in mice homozygous for the deleted V beta gene, indicating that neither V beta gene segment identified in previous studies is required for diabetogenesis in unmanipulated diabetes-prone mice. PMID- 1936614 TI - Characterization of endothelin receptors and effects of endothelin on diacylglycerol and protein kinase C in retinal capillary pericytes. PMID- 1936615 TI - Pancreas transplantation in humans with diabetes mellitus. AB - Pancreas transplantation, when successful, is a reproducibly effective method to normalize glycemia without the use of exogenous insulin treatment in patients with diabetes mellitus. Success rates for combined pancreas and kidney transplantation are approximately 70%, and patient survival rates are approximately 90% 1 yr postoperatively. Metabolic benefits of this procedure include normalization of levels of fasting plasma glucose and HbA1C. Glucose induced insulin secretion and intravenous glucose tolerance are normalized. Improvements are also observed in glucose recovery after insulin-induced hypoglycemia and in glucagon secretion during hypoglycemia. Pancreas transplantation is also associated with normalization of kidney structure and both motor and sensory nerve function. However, no benefits have been observed with regard to pancreatic polypeptide secretion, kidney function, and the retinal pathology of diabetes mellitus. Pancreas transplantation has reached a point in its history where the operative technique and its ancillary medical therapy have been optimized. Improvement in the rates of success, morbidity, and mortality will probably depend on improvement in immunosuppressive drugs and the physical condition of the recipients themselves. The time is at hand when we need to carefully consider whether it is ethical and advisable to make pancreas transplantation available to individuals who have fewer chronic complications of diabetes mellitus. Future studies of pancreas transplantation must incorporate more rigid experimental controls than have been used in the past to better assess the relative merits of this procedure. PMID- 1936616 TI - Endoneurial microvessels in human diabetic neuropathy. Endothelial cell dysjunction and lack of treatment effect by aldose reductase inhibitor. AB - Endoneurial microvascular abnormalities have been invoked in the pathogenesis of diabetic distal symmetric polyneuropathy. Detailed morphometric analysis of the endoneurial microvasculature was correlated with previously published data on nerve fiber morphometry and teased fiber analysis obtained from the same sural nerve biopsies. Biopsy specimens from neuropathic diabetic patients were obtained before and after 12 mo of aldose reductase inhibitor (ARI) treatment and compared to 15 carefully age-matched control subjects. Diabetic microvessels showed basement membrane thickening and loss of endothelial cell tight junctions. Microvascular density and the frequency of microvessels closed by endothelial cells increased with age in diabetic and control nerves and were unaffected by diabetes. The density of microvessels showing patent lumina did not differ between control and diabetic subjects and was not related to age or diabetes. Closed microvessels were composed of postcapillary venules that were otherwise devoid of ultrastructural abnormalities. We suggest that microvascular closure by endothelial cells may be a physiological condition and is unlikely to have any pathogenetic significance in diabetic neuropathy. Based on the current limited biopsy material, we conclude that 12 mo of ARI treatment that induced significant fiber repair and regeneration had no detectable effect on endoneurial microvascular abnormalities. These data suggest that endoneurial vascular pathology is not a rate-limiting factor in fiber damage or repair at this stage of diabetic neuropathy. PMID- 1936617 TI - Decreased bronchial response to methacholine in IDDM patients with autonomic neuropathy. AB - This study was designed to evaluate the involvement of airways innervation during diabetic autonomic neuropathy. Bronchial response to methacholine was assessed by inhalation of serially doubling doses in 22 insulin-dependent diabetes mellitus (IDDM) patients and 11 nondiabetic control subjects selected for their nonsmoking habits. Cardiovascular autonomic control was studied by four standardized tests, i.e., blood pressure and heart-rate variations during orthostatism, heart-rate variation during Valsalva maneuver, and deep breathing. Magnitude and time-course of response to methacholine were similar in nondiabetic subjects and IDDM patients without any abnormal result on cardiovascular tests. Conversely, bronchial response to methacholine was markedly reduced in IDDM patients with one or more abnormal results by cardiovascular assessment of autonomic control. In the IDDM patients, bronchial response to methacholine was significantly correlated to indexes of cardiovascular autonomic control. These results suggest that, during diabetic neuropathy, innervation of the airways likewise involves cardiac autonomic control and leads to impairment of defense reflexes of the airways. PMID- 1936618 TI - Skeletal malformations in rat offspring. Long-term effect of maternal insulin induced hypoglycemia during organogenesis. AB - We studied the effect of maternal hypoglycemia on skeletal growth in the offspring of nondiabetic and diabetic rats. Female Wistar rats were injected with streptozocin (30 mg/kg i.v.) 2-3 wk before mating, and diabetes was confirmed by an intraperitoneal glucose tolerance test. On postconception day 9.5 or 10.5, both control and diabetic dams received saline or Actrapid human insulin (400 mU/rat i.p.). Hypoglycemia (approximately 2.8 mM) was induced for 120 min in the insulin-treated mothers. Pregnancy was terminated on gestational day 20. Fetal bones and cartilage were double-stained with alizarin red S and alcian blue 8GS. Insulin-induced hypoglycemia caused delayed ossification in the fetuses of the control dams. The number of malformations, e.g., costal fusion waves, increased greatly. These effects were more striking in the fetuses of dams that had received insulin on day 10.5 rather than on day 9.5 of embryo development. This type of insulin-induced hypoglycemia further delayed ossification of the fetal bones in diabetic dams. The influence of maternal hypoglycemia on skeletal malformations and/or variations was greater in the fetuses of diabetic dams than in the fetuses of control dams. These data suggest that maternal hypoglycemia in early pregnancy has a striking effect on skeletal growth and malformations in fetuses. In addition, mild glucose intolerance in dams may amplify these hypoglycemic effects. PMID- 1936619 TI - Detection of inner retina dysfunction by steady-state focal electroretinogram pattern and flicker in early IDDM. AB - The effects of diabetes on the neural retina before the onset of clinically detectable retinopathy can be investigated with electrophysiological methods. Our aim was to detect early retinal dysfunctions in 60 patients with insulin dependent diabetes mellitus (IDDM) and with a short duration of disease. We used the steady-state focal (9 degrees field size) electroretinogram (ERG) of the macula in response to luminance modulation of a uniform field (flicker ERG) or to counterphase-modulated sinusoidal gratings (pattern ERG). The harmonic analysis of flicker ERG and pattern ERG yielded three main components: a first and a second harmonic to flicker (1F and 2F, respectively) and a second harmonic to pattern (2P). The 1F is believed to be correlated to photoreceptor activity, whereas 2F and 2P represent different subsets of generators in the inner retina. Results of focal ERG in IDDM patients with no or early retinopathy were compared with age-matched control subjects. Mean 2F and 2P amplitudes were significantly reduced in IDDM patients compared with the control group (P = 0.0001 by analysis of variance). 2P but not 2F amplitude was significantly more reduced in patients with retinopathy than in those without retinopathy (P less than 0.05). 2F but not 2P phase abnormalities were observed in some patients. 2F and 2P alterations were slightly correlated with metabolic control (r = 0.22, P = 0.02) and disease duration (r = 0.28, P = 0.003). 1F was not significantly altered in IDDM patients. Our results suggest that early diabetes causes selective neurosensory deficits of inner retina layers, whereas the photoreceptors appear unaffected. PMID- 1936620 TI - Reactivity to human islets and fetal pig proislets by peripheral blood mononuclear cells from subjects with preclinical and clinical insulin-dependent diabetes. AB - A simple, direct assay for T-lymphocyte reactivity to islet antigen(s) in human insulin-dependent diabetes mellitus (IDDM) should facilitate preclinical diagnosis and the evaluation of intervention therapy to avert autoimmune-mediated beta-cell destruction. In subjects with preclinical or clinical IDDM, we measured the reactivity of peripheral blood mononuclear cells (PBMCs) incubated over 6 days with either adult human islets or fetal pig proislets, or other fetal pig tissues, and with human insulin. With islets, the stimulation index (SI) of [3H]thymidine uptake by PBMCs exceeded the mean + 2SD of control subjects in 6 of 6 preclinical subjects (SI 8.7 +/- 3.7), 7 of 11 clinical subjects (SI 5.2 +/- 3.4), and 1 of 12 control subjects (SI 2.7 +/- 1.7); with insulin, the responses were less in frequency and magnitude, being 4 of 6 (2.7 +/- 1.6), 3 of 11 (2.2 +/ 1.1), and 0 of 12 (1.20 +/- 0.55), respectively. The mean responses to islets of PBMCs from preclinical and clinical subjects differed significantly from control subjects (P less than 0.02 by 2-tailed Kruskal-Wallis test). Secretion of granulocyte macrophage colony-stimulating factor by PBMCs over 6 days was assayed in the preclinical group and generally paralleled the uptake of [3H]thymidine. PBMC reactivity to islets appeared to be at least as sensitive a marker of preclinical IDDM as autoantibodies to a 64,000-Mr protein, presumably the enzyme glutamic acid decarboxylase, in fetal pig proislets. In conclusion, islet reactive T lymphocytes in subjects with preclinical and clinical IDDM can be identified in bulk culture of PBMCs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936622 TI - HLA-associated insulin autoantibody formation in newly diagnosed type I diabetic patients. AB - To assess a possible HLA association with anti-insulin autoantibodies (IAAs) in human insulin-dependent (type I) diabetes, 51 newly diagnosed type I diabetic patients (mean age 22 +/- 8 yr) were typed for HLA-DR and HLA-DQ and studied for IAAs before exogenous insulin therapy with a competitive radioimmunoassay (normal range less than or equal to 49 nU/ml). The level of IAAs in 16 patients exceeded our upper limit of normal, and 18 had high-titer islet cell antibodies (ICAs; greater than or equal to 40 Juvenile Diabetes Foundation U). A striking association with HLA-DR4 (DQw3) in both the prevalence and the level of IAAs was found (IAA positivity in patients with DR4/4 vs. DR4 heterozygous vs. non-DR4: 90 vs. 29%, corrected [c] P less than 0.01, vs. 5%, Pc less than 0.0001; IAA positivity in patients with DR4 vs. non-DR4: 50 vs. 5%, Pc less than 0.005; IAA level in patients with DR4/4 vs. DR4 heterozygous vs. non-DR4: 111 vs. 17 nU/ml, Pc less than 0.01, vs. 20 nU/ml, Pc less than 0.0001; IAA level in patients with DR4 vs. non-DR4: 45 vs. 20 nU/ml, Pc less than 0.01). In contrast, none of the DR3+ subjects had IAAs above normal range, except in conjunction with DR4 (DR3 vs. non-DR3: 12 vs. 42%, Pc less than 0.05). However, there was no significant relationship between DR3 and IAAs after correcting for the number of DR4 alleles. No relationship was seen between age of onset, IAA level, and HLA typing in our population, and no relationship was found between ICA positivity and HLA antigens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936621 TI - Renal adaptation to dietary phosphate restriction in rats. Interactions with insulin and calcitriol. AB - Insulin may contribute to the increase in tubular reabsorption of phosphate during dietary phosphate restriction. Moreover, insulin is required for the stimulation of calcitriol under this experimental condition. To evaluate whether calcitriol plays a role in the antiphosphaturic effect of insulin during phosphate restriction, phosphate uptake was measured in brush border membrane vesicles (BBMVs) obtained from the following six experimental groups of rats: normal (0.8%)-phosphate diet for 1 wk, low (0.03%)-phosphate diet for 1 wk, normal-phosphate diet for 1 wk and streptozocin 48 h before the experiment, low phosphate diet for 1 wk and streptozocin 48 h before the experiment, low phosphate diet and streptozocin and exogenous insulin, and low-phosphate diet and streptozocin and exogenous calcitriol. BBMV phosphate uptake was higher in the nondiabetic rats on a low-phosphate diet than in the controls on a normal phosphate diet. BBMV phosphate uptake was not different between diabetic rats on a normal-phosphate diet than in nondiabetic controls on the same diet. In contrast, BBMV was significantly lower in diabetic rats on a low-phosphate diet than in nondiabetic controls on the same diet. Exogenous insulin but not calcitriol restored the increase in BBMV phosphate uptake in diabetic rats on a low-phosphate diet. Plasma calcitriol levels were increased threefold in nondiabetic rats fed a low-phosphate diet. Streptozocin-induced diabetes abolished the adaptive increase in plasma calcitriol. Exogenous insulin and calcitriol administration to diabetic rats on a low-phosphate diet resulted in similar increases in plasma calcitriol levels. These results suggest that, during dietary phosphate restriction, insulin stimulates renal phosphate retention independently of its effect on calcitriol. PMID- 1936623 TI - Presence of insulin autoantibodies as regular feature of nondiabetic repertoire of immunity. AB - With an ultrasensitive noncompetitive enzyme-linked immunosorbent assay (ELISA), we tested the hypothesis that the presence of insulin autoantibodies in nondiabetic individuals is a normal event. Plasma and peripheral blood mononuclear cells were obtained from 50 nondiabetic whites for determination of insulin autoantibodies by ELISA and radioimmunoassay (anti-insulin IgG [AI-IgG] and 125I-labeled insulin bound [%]), islet cell antibodies, anti-nuclear antibodies and rheumatoid factor, and HLA class II-type antigens (DR, DRw, and DQ). The range of 125I-insulin binding was significantly less than was seen in pretreatment sera from individuals with diabetes (from -0.4 to 0.4% vs. -0.8 to 7.7%, respectively, P = 0.001). Eighty-eight percent of these nondiabetic individuals had significant levels of AI-IgG with preferential binding to human insulin. The geometric mean of AI-IgG concentrations in individuals with significant levels was 180 pM. Binding to human insulin was seen in 88%, to pork insulin in 42%, and to beef insulin in 24% of individuals (P less than 0.001 overall; P less than 0.05 where more bound to pork than beef insulin). Binding of AI-IgG to human insulin-coated plates was substantially inhibited by preincubation with human insulin (median inhibition 57.6%) with little if any inhibition by glucagon, C-peptide, albumin, or IgG. Four individuals had highly specific human AI-IgG as shown by immunoaffinity studies. AI-IgGs were significantly higher in individuals with the HLA haplotype DR4,DRw53,DQ3 and lower in individuals with DR5,DRw52,DQ1 (P = 0.03 for both).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936624 TI - Effect of epinephrine on pancreatic beta-cell and alpha-cell function in patients with NIDDM. AB - The purposes of this study were to determine whether patients with non-insulin dependent diabetes mellitus (NIDDM) have an enhanced glycemic response to epinephrine (EPI) and to quantitate the effect of physiological elevations of EPI on pancreatic islet function in these patients. The increment of plasma glucose (PG) in response to 45 min of EPI infusion (mean plasma EPI 2490 pM) was more than twofold greater in nine NIDDM patients than in 20 nondiabetic control subjects (mean +/- SE delta PG 3.9 +/- 0.3 vs. 1.7 +/- 0.1 mM, P less than 0.0001). The effects of EPI on beta-cell and alpha-cell function were compared in nine NIDDM patients and 9 age- and weight-matched control subjects during infusions of saline or two doses of EPI on separate days (mean plasma EPI 270, 1120, and 2490 pM). On each day, the acute insulin response (AIR) and acute glucagon response (AGR) to 5 g i.v. arginine were measured at three matched steady-state PG levels (means of 9, 14, and 29 mM). Beta-Cell sensitivity to glucose (slope of glucose potentiation) and beta-cell secretory capacity, or AIRmax (AIR at the highest clamped PG level), were calculated. In control subjects, EPI inhibited the AIR at PG concentrations of 9 and 14 mM (both P less than 0.05) but had no effect on the AIRmax, resulting in a rightward shift of the curve relating the AIR and PG and a decrease in the slope of glucose potentiation (P less than 0.01). In contrast in NIDDM patients, EPI inhibited the AIR at all PG levels, including the AIRmax (all P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936625 TI - Prevention of cyclophosphamide-induced and spontaneous diabetes in NOD/Shi/Kbe mice by anti-MHC class I Kd monoclonal antibody. AB - The immune mechanisms directly responsible for beta-cell destruction in insulin dependent diabetes are undefined. We studied the role of MHC class I-restricted T lymphocytes in the development of diabetes in cyclophosphamide (CY)-treated male and untreated female NOD mice (H-2Kd,Db). After administration of CY to 10-wk-old male NOD/Shi/Kbe mice, 37 of 64 (58%) phosphate-buffered saline-injected control mice and 13 of 22 (59%) anti-Kb and 12 of 27 (44%) anti-Db monoclonal antibody (MoAb)-injected mice became diabetic by 14 wk of age, whereas only 3 of 38 (8%) anti-Kd and 2 of 13 (15%) anti-Lyt-2 MoAb-injected mice did. In untreated female NOD/Shi/Kbe mice, 30 of 46 (65%) mice developed spontaneous diabetes by 30 wk of age, whereas none of 9 anti-Kd MoAb-injected mice became diabetic. Immunohistochemical studies showed that islet-infiltrating cells in CY-treated control mice were composed mainly of both L3T4+ and Lyt-2+ T lymphocytes, whereas many L3T4+ and very few Lyt-2+ lymphocytes infiltrated within the islets in anti Kd MoAb-injected mice. Administration of anti-Lyt-2 MoAb induced the absence of Lyt-2+ T lymphocytes in the islet and spleen. However, anti-Kd MoAb did not change the number of spleen cells or the T-lymphocyte subset and response to concanavalin A. These results suggest that MHC class I Kd-restricted Lyt-2+ T lymphocytes play an important role as direct effector cells in destruction of beta-cells in NOD/Shi/Kbe mice. PMID- 1936626 TI - Purification and preliminary characterization of new peptide inhibitor of insulin from pork pancreas. AB - A new active peptide was purified from the acid-alcohol extract of pork pancreas. It markedly suppressed the insulin activity detected by either in vivo mouse convulsion assay or in vitro free-fat cell assay. When the extract was subjected to chromatography on a carboxymethylcellulose column, the insulin fraction completely passed through the column, whereas the glucagon fraction was absorbed. The fact that the total apparent biological activity of insulin in the exclusive eluate was higher than in the original extract and the insulin radioimmunoactivity remained unchanged led to the discovery of a potent insulin inhibitor in the extract. The inhibitor was separated from glucagon and insulin in the extract by ion-exchange chromatography on a carboxymethylcellulose column followed by gel filtration on a Bio-Gel P-6 column and finally purified by reverse-phase high-performance liquid chromatography (HPLC) on a C-18 column. The antagonistic effect of this inhibitor on insulin was dose dependent with an ED50 of 2 x 10(-10) M, which was the same level used for insulin in vitro assay (1.7 x 10(-10) M). Amino acid analysis of the inhibitor showed that it was rich in arginine and glycine. It was estimated to be approximately 3000 Mr. The NH2 terminal of the peptide was proved to be blocked because it could not be degraded by Edman degradation. Based on the physicochemical and biochemical characteristics of the inhibitor and compared with other active peptides known to be in the pancreas, the inhibitor is probably a new active peptide that might play an important role in homeostasis of carbohydrate metabolism. PMID- 1936627 TI - A commitment to excellence and a willingness to change. PMID- 1936628 TI - What children see affects how they read. AB - Children of mixed abilities were given three single-word lists to read, matched for linguistic complexity. The visual component of the task was made harder by reducing the print size with each new list. The reading errors made by children who did and who did not have a visual impairment were compared. The visually impaired children's pattern of reading errors changed as their vision was stressed by the reduction in print size; their errors became non-words (neologisms). This finding suggests a link between the efficiency of visual processing and the accuracy of reading of these children. PMID- 1936629 TI - Neuropsychological deficits in adults with dyslexia. AB - Adults with severe dyslexia were compared with age-, sex-, IQ- and SES-matched controls on a neuropsychological and neuromotor test battery, and a contrast group who had recovered from dyslexia was also included. The severely dyslexic group was substantially impaired on tests of verbal fluency and learning, as well as on non-verbal temporal order judgements. These test scores were strong predictors of the degree of reading impairment, as was the rate of repetitive movement of the right hand and foot. The results suggest that adult dyslexia is not 'isolated', but is one expression of a widespread left-hemisphere dysfunction. PMID- 1936630 TI - Tactile extinction in childhood hemiplegia. AB - Tactile extinction was investigated by the Quality Extinction Test (QET) of Schwartz in 39 patients, 34 of whom had congenital hemiplegia and five early acquired hemiplegia. Extinction values were significantly higher in hemiplegia patients than in controls and usually contralateral to the side of brain damage, except for four cases with right hemiplegia. Values were also higher in males than in females. There were no significant differences between patients with left and right hemiplegia, and no correlations between extinction and IQ or the presence of epilepsy. There was a correlation between QET scores and neuroradiologically proven cerebral atrophy. The meaning of extinction in hemiplegic patients and the principal theories regarding the pathogenesis of neglect are discussed. PMID- 1936631 TI - Ammonia and carnitine concentrations in children treated with sodium valproate compared with other anticonvulsant drugs. AB - Plasma ammonia was measured in 59 children requiring anticonvulsant drugs: 37 children (group 1) on sodium valproate alone or in combination with other drugs and 22 children (group 2) on drugs other than sodium valproate. Plasma ammonia was higher in group 1 children. Total and free carnitine was measured in plasma and erythrocytes of all children and in the urine of 16 children from group 1 and eight from group 2. Plasma and erythrocyte free carnitine was significantly lower in the children on sodium valproate, along with a significant increase in the ratio of acyl (bound) carnitine to free carnitine. No significant correlation was found between plasma ammonia and carnitine concentrations for either group of children. Plasma and erythrocyte concentrations were not related. Urinary free carnitine was reduced in children treated with valproate, with a significant increase in the ratio of bound to free carnitine. Carnitine supplementation is discussed. PMID- 1936632 TI - Prognosis for seizure control and remission in children with myelomeningocele. AB - A combined retrospective and prospective study was designed to determine the incidence of seizures in 140 children with myelomeningocele, as well as the potential for seizure control and remission. The incidence of seizures in 109 patients with myelomeningocele and hydrocephalus was 16.5 per cent, and 19.4 per cent in a further 31 patients without hydrocephalus. Mental retardation, often in combination with cerebral malformations, was significantly more common in children with seizures, regardless of presence or absence of hydrocephalus. Of the 24 patients with convulsion, three-quarters had anti-epileptic medication discontinued, without recurrence of seizures. An additional five children's seizures are well controlled with medication. Mental retardation was the only significant predictor of long-term outcome. These results indicate that children with myelomeningocele have an excellent prognosis for seizure control and subsequent remission off medication. PMID- 1936633 TI - A sibling-controlled study of intelligence and academic performance following Reye syndrome. AB - The authors compared the intellectual, cognitive and academic abilities of 22 survivors of Reye syndrome attending normal schools with the sibling nearest in age as control. The British Ability Scales, visual and verbal IQ, short-term memory scales and attainment tests were administered to all children. Reye syndrome children as a group differed significantly from the controls only on the basic number skills test. However, children with severe encephalopathy and those whose illness occurred in infancy had significant deficits on many of the tests. 18 children recovered without requiring 'additional educational provision'; the mean IQ of the 22 Reye syndrome children was 101. Nonetheless, these children's poor performance on the basic number skills test has important implications for teachers, and careful monitoring of future educational performance is essential. PMID- 1936634 TI - Neonatal sensorineural hearing loss associated with furosemide: a case-control study. AB - Thirty-five neonates with sensorineural hearing loss (SNHL), identified by brainstem auditory evoked response (BAER), and 70 matched controls with normal BAERs were studied. All infants had had BAERs before discharge from hospital as part of a screening program for high-risk neonates. Infants with SNHL showed no response to a 60dBnHL click stimulus and all had these results confirmed on at least one occasion after hospital discharge. Based on the screening program results, over-all prevalence of non-hereditary hearing loss was estimated to be 0.93 per 1000 live births, and in neonates weighing less than 2000g at birth to be 15.54 per 1000 live births. Several factors, including seizures, exposure to anticonvulsant drugs, furosemide and kanamycin were associated with SNHL, but after multivariate analysis, only exposure to furosemide remained significant. Peak serum bilirubin concentration and benzyl alcohol exposure did not appear to be related to hearing loss. PMID- 1936635 TI - Variable course of Canavan disease in two boys with early infantile aspartoacylase deficiency. AB - This is a report of two patients with Canavan disease from the Federal Republic of Germany. One is a severely retarded, macrocephalic boy, who had the characteristic laboratory findings of Canavan disease and progressive leucodystrophy on neuro-imaging. The other is retarded, with signs of a cerebral movement disorder showing no deterioration during the first 15 months. The significance of aspartoacylase deficiency in Canavan disease for differential diagnosis, genetic counselling and prenatal diagnosis of leucodystrophy is discussed. PMID- 1936636 TI - The brain and the immune system. PMID- 1936637 TI - Marginal adaptation of nine commercial intermediate resins. AB - The bonding efficacy of nine commercially available intermediate resins was examined by measuring the maximum contraction gap of a light-activated composite in a cylindrical cavity of human dentin. With only one exception, the marginal adaptation of the composite improved significantly when the intermediate resins were combined with an experimental dentin cleaning system of the neutralized 0.5 mol/L EDTA and a dentin primer composed of a 35% aqueous solution of either hydroxyethyl methacrylate (HEMA) or glyceryl methacrylate (GM). Complete marginal adaptation was obtained with four tested materials when dentin was pre-treated with EDTA and GM. PMID- 1936638 TI - Quality and durability of marginal adaptation in bonded composite restorations. AB - Excellent marginal adaptation extends the longevity of restorations. Unfortunately, polymerization shrinkage of composite restorations adversely affects this quality requirement. The residual stress within the cured resin compromises the material's properties, causes marginal openings, and flexes cavity walls. In this study, the wall-to-wall contraction in MOD cavities was measured for different placement techniques. In addition, the restoration margins were quantitated before and after thermo-cycling and mechanical stressing. Factors which enhanced adaptation also optimized marginal quality and reduced the amount of residual stress. The latter was expressed by intercuspal narrowing after the restoration was completed. Both quality and stress resistance of the marginal adaptation were inversely correlated to the intercuspal narrowing caused by the polymerization contraction of bonded and excellently adapted resin restorations. The most effective factors which optimized marginal quality included: guidance of the shrinkage vectors; reducing the ratio of bonded to free, unbonded restoration surfaces; and minimizing the mass of in situ-cured composite. The latter principle was followed best in the adhesive inlay technique. In medium-sized adhesive MOD composite inlays, the volume loss induced by the polymerization contraction of the composite cement was non-destructively compensated for by an inward flexing of each cavity wall of approximately 10 microM. PMID- 1936639 TI - Radiopacity of restorations and detection of secondary caries. AB - The aim of this study was to compare the accuracy of radiographic diagnosis of secondary carious lesions adjacent to filling materials with different radiopacities. Class II preparations were made in extracted teeth. One group of teeth (n = 49) had caries in the gingival wall, simulating secondary caries. The control teeth (n = 29) had no caries. Three posterior composite materials (P-30 and two experimental composites) with different radiopacities and amalgam were successively inserted into each cavity. After being radiographed, the "restorations" were removed and a new material inserted. The radiographs were interpreted by 11 dentists, and secondary caries was diagnosed according to a five-point confidence rating. The results obtained with the receiver operating characteristics (ROC) method showed that a semi-radiopaque restoration seemed favorable and that the best radiopacity slightly exceeded that of enamel. PMID- 1936640 TI - Filler systems based on calcium metaphosphates. AB - Calcium metaphosphates (CMP's)--a unique class of phosphate minerals possessing polymeric structures, [Ca(PO3)2]n, and having refractive indices of approximately 1.54-1.59-- are optically compatible with resins such as BIS-GMA. In this study, several types of CMP's were prepared and evaluated for their potential as fillers for visible-light-activated (VLA) dental composites. The vitreous (V) and beta crystalline forms of CMP were prepared by controlled thermolysis of monocalcium phosphate monohydrate, Ca(H2PO4)2.H2O. Hybrid fillers were also prepared by thermal methods. Fillers, characterized by IR spectroscopy and optical microscopy, were prepared in several size ranges (e.g., 1-100 microns). VLA composites were formulated by use of both untreated and surface modified CMP's. V CMP and its hybrids yielded composites which expanded when stored in water but were of low strength, e.g., diametral tensile strength, (DTS) = 8 MPa. beta-CMP composites were more moisture-resistant, had higher DTS's (from 12 to 33 MPa), and showed a tendency to arrest brittle fracture. These novel fillers have potential uses in resin-based materials such as dental composites, cements, and adhesives. PMID- 1936641 TI - Bonding of a light-curing glass-ionomer cement to dental amalgam. AB - In the clinical situation, the need may arise for placement of a glass-ionomer cement over an existing amalgam restoration. This study assessed the tensile bond strength of a recently developed light-curing glass ionomer (Vitrabond) to dental amalgam (Dispersalloy), with and without the use of Scotchbond dual cure as an intermediary. Amalgam adherend specimens were prepared, then aged in water at 37 degrees C for seven days. Immediately before being bonded, the amalgam surfaces were finished flat on 600-grit paper. Forty specimens were used for bonding in this condition, and another 40 were covered with a thin layer of Scotchbond, which was light-cured for 10 s. The glass-ionomer was applied to the adherend surface in two increments, each light-cured for 30 s. After being bonded, half the specimens were stored in water at 37 degrees C, while half were stored in an environment of 95 +/- 5% RH at 37 degrees C. The 24-hour tensile bond strengths, in MPa, were: for specimens stored in water, without Scotchbond 8.4 +/- 1.2, with Scotchbond 4.7 +/- 1.3%; and for specimens stored in 95 +/- 5% RH, without Scotchbond 9.2 +/- 2.1, with Scotchbond 4.6 +/- 1.5. The data were further analyzed by the Weibull distribution function. It was concluded that a strong reliable bond can be achieved between Vitrabond and set Dispersalloy, and that the use of Scotchbond as an intermediary is contra-indicated. PMID- 1936642 TI - Physiological aging of an all-ceramic restorative material. AB - Ceramic materials exposed to a liquid environment may be subject to stress corrosion and/or time-delayed failure. The intent of this project was to evaluate the susceptibility of a magnesia alumina spinel (Cerestore) to stress corrosion and degradation. Bars 2.5 x 2.5 x 30.0 mm were prepared according to manufacturer's instructions. Specimens were aged in distilled water or air at 37 degrees C. The modulus of rupture was evaluated at zero, six, and 12 months in four-point loading at loading rates of 0.05, 0.5, and 5.0 mm/min. The modulus of rupture of each specimen was tested in its respective aging medium. The data were analyzed by one-way analysis of variance with a multiple-means comparison test, linear regression analysis, and Weibull statistics. The pooled data sets of specimens aged in water vs. those aged in air showed a significant difference in the respective modulus of rupture (air, 108.50 +/- 16.11; water 96.94 +/- 15.04 MPa). The one-way analysis of variance showed no significant difference between the aging times zero, six, and 12 months in each respective aging medium. The Weibull analysis also showed no difference between the Weibull constants, 7.66 air vs. 7.64 water, but a significant difference between the characteristic strengths, 115.22 air vs. 103.02 water. This study indicates that distilled water has a significant degradative effect on a magnesia alumina spinel, more likely affecting the mode of fracture rather than the stress corrosion characteristics. PMID- 1936643 TI - Gel strength and rate of gelation of soft polymers. AB - A rheometer was used to characterize the gelation rate of six commercial short- to medium-term (chairside intra-oral gelation) denture soft-lining materials. Shear puncture force was measured from one to 60 days for six short- to medium term materials as well as for three heat-cured (polymerizable) materials. The observed increase in puncture force with age of the specimen was considered to be a function of increased polymer chain entanglement and/or loss of plasticizer. Reduction in puncture force with age occurred for some materials as a result of hydration of the polymer gel. Rheometer setting time (gelation rate) and puncture force values for the intra-oral gelation materials were influenced by the quantity of ethyl alcohol present in the mixing liquid. In general, the higher the level of ethyl alcohol, the shorter the gelation time and the stronger the gel. The characterization of the properties may help develop improved prosthodontic treatment procedures, and allow better management of soft-tissue recovery following trauma. PMID- 1936644 TI - Correlation of in vivo and in vitro performance of adhesive restorative materials: a report of the ASC MD156 Task Group on Test Methods for the Adhesion of Restorative Materials. AB - Before a standard designed to test the adhesion of adhesive restorative materials can be accepted, it is necessary to identify those parameters which are of clinical relevance and which can be studied under in vitro testing conditions. The goal of this report has been to identify information related to how dentinal fluid, intra-tubular pressure, polymerization shrinkage, cavity preparation, cavity shape, placement technique, curing method, tooth age, environmental conditions, masticatory forces, thermal cycling, and microleakage influence the bond strength++ of adhesive restorative materials. This review is also intended to function both as an information base of past experimental data as well as a source of guidance for further, needed research. PMID- 1936645 TI - Comparison of the sealing ability of four cavity varnishes: an in vitro study. AB - The purpose of this study was to test and to compare, in vitro, the sealing ability of four different cavity varnishes used to minimize the marginal leakage of amalgam fillings. For this purpose, a model was developed in order to avoid quality-deteriorating effects (such as condensation forces used during placement of amalgam) and temperature changes. In this model, raw ceramic disks were used instead of dentin. The four varnishes showed significant reducing effect on the penetration of the dye (Methylene Blue) compared with the control. There was no cavity varnish with optimal sealing. PMID- 1936646 TI - Spreading of oligomers on polymers. AB - The successful repair of a composite restoration may depend on the ability of a repair composite to spread on the restoration to be repaired. The purpose of this study was to measure the spreading of four oligomers on their polymers. The oligomers were: ethoxylated bisphenol A dimethacrylate (EB), BisGMA/3EDMA:70/30 (ED), BisGMA-Nupol (NU), and urethane dimethacrylate (UD). Polymer strips were made from these oligomers by light-curing. Spreading was calculated from measurements of the contact angle of the oligomers on the polymers, the surface tension of the oligomers, and the viscosity of the oligomers. In this model system, values of spreading of EB, ED, UD, and NU on oligomer ED were: 2.8, 1.4, 0.24, and 0.0009 cm/s, respectively. The spreading by oligomers EB, ED, and UD on polymer ED was slightly higher than that on polymer UD. PMID- 1936647 TI - Performance of occlusin in butt-joint and bevel-edged preparations: five-year results. 4. AB - The five-year findings of a study to compare the performance of restorations of Occlusin (ICI Dental, Macclesfield, UK) in butt-joint and bevel-edged preparations are reported. Ninety-four (79%) of the restorations originally placed were reviewed at five years, 20 restorations (17%) having failed during the study. Initial analysis of the overall results having failed to reveal any significant differences between the five-year performance of the two types of restorations, the results were combined and analyzed by Chi-square tests and step wise logistic regression. Chi-square analysis indicated that of the independent variables investigated, size of restoration had the greatest effect on clinical performance. Step-wise logistic regression revealed that only four of the eight dependent variables investigated showed significant predictive relationships with the independent variables, the logistic equation for occlusal marginal adaptation being the most complex. The greatest amount of generalized occlusal surface wear tended to be seen in large-sized Class II restorations in molar teeth, with the main factor influencing wear being found to be the type of restoration (Class I or Class II). It is concluded that the performance of restorations of Occlusin has not been found to differ significantly in butt-joint and bevel-edged preparations after five years in clinical service. Step-wise logistic regression has been found to be a useful tool in the analysis of data obtained during the clinical evaluation of a restorative material. PMID- 1936649 TI - European Pancreatic Club, XXIIIrd meeting, Lund, September 16-18, 1991. Abstracts. PMID- 1936648 TI - Strength of phosphate-bonded investments at high temperature. AB - There has been little reported on the strength of phosphate-bonded investments, and in particular the role of 'special liquids' in this context is poorly understood. Using a novel test design, sequential testing of an investment diaphragm using a variable casting metal mass, a measure of the effect of 'special liquid' on strength under actual casting conditions has been obtained. The use of special liquid was found to increase substantially the strength of the four products tested. This test may provide more useful data than the conventional compressive strength test, which may give misleading information, especially if performed at room temperature. PMID- 1936650 TI - Botwood: Newfoundland's health care centre--a rural success. PMID- 1936651 TI - [A total program of emergency measures in a hospital setting]. AB - A seven-step approach to structure emergency planning has helped Montfort Hospital in Ottawa to promote prevention and achieve a higher degree of preparedness. The seven steps include: using the mission statement to form goals and objectives; creating an organizational structure to delegate responsibilities; upgrading systems to comply with existing codes and standards and to include their costs in annual budgets; compiling main, secondary and condensed emergency plan manuals for different levels of staff; planning activities to stimulate staff interest and promote the program; training staff and evaluating the process. A collective approach to emergency planning and a prepared facility should result from the implementation of a comprehensive emergency measures program. PMID- 1936652 TI - New technology, physical facilities and the environment. AB - Technology assessment is already a powerful tool for dealing with issues of appropriateness and effectiveness of clinical technology; it can be significantly enhanced as a valuable process if it is extended to deal with issues of how best to integrate the considered technology with the physical environment and facilities in which it will be used. These issues include: staff and patient safety and comfort; code compliance; effective accommodation of work flow; staff training; and ongoing operational costs. The methodology of technology assessment can effectively assist health facility administrators in evaluating the appropriateness and effectiveness of energy conservation projects and in addressing environmental concerns. The constraints in funding available to the health care system will continue to challenge the creative energies of our managers to encourage them to develop innovative ways, using technology assessment, to make the physical facilities and environment safe, economical and comfortable for patients and staff. PMID- 1936653 TI - Designing for patient comfort: a renovation at the Perley Hospital. PMID- 1936654 TI - Investment practices at acute care institutions: a survey. PMID- 1936655 TI - A hospital capital price index. AB - This paper describes the development of a price index for hospital equipment. Based on 10 years of hospital capital acquisition data from a large teaching hospital, equipment acquisitions were categorized and weights derived for each category. Using national producer price indexes for each of these categories, a national hospital equipment index was derived for 1981 to 1991. Forecasts for 1991 and 1992 were then made. The resulting index indicated that price movements of our hospital capital equipment index were very similar to the Implicit Gross Domestic Product Deflator, an index that measures price changes for the nation's Gross Domestic Product. However, because of the relative importance of several categories of equipment (scientific instruments, computers), more widespread data on hospital equipment expenditure patterns would be desirable in order to validate these results. PMID- 1936656 TI - Glucose tolerance and plasma insulin response to intravenous glucose infusion and test meal in rats with microencapsulated islet allografts. AB - Albino Oxford rats made diabetic with 75 mg/kg streptozotocin were intraperitoneally transplanted with 2500-2900 alginate-polylysine microencapsulated Lewis islets (n = 9, total islet tissue volume 8.0-11.0 microliters), or a similar volume of non-encapsulated Lewis islets (n = 5). All rats with microencapsulated islets became normoglycaemic, and remained normoglycaemic for 5-16 weeks. In rats with non-encapsulated islet grafts, only a temporary decrease in blood glucose was observed, and all were again severely hyperglycaemic at 1 week after implantation. At 5-6 weeks after transplantation, glucose tolerance in rats with microencapsulated islets was tested by intravenous glucose infusion (10 mg/min over 20 min) and test meal administration (n = 4). During glucose infusion, maximum glucose levels were 13.0 +/- 0.4 mmol/l in rats with microcapsules and 8.9 +/- 0.4 mmol/l in healthy control rats (p less than 0.01). Concomitant maximum plasma insulin levels were 215 +/- 17 pmol/l in rats with microcapsules and 715 +/- 85 pmol/l in controls (p less than 0.001). After the test meal, maximum blood glucose was 10.6 +/- 0.9 mmol/l in rats with microcapsules and 6.2 +/- 0.1 mmol/l in controls (p less than 0.001), with concomitant maximum plasma insulin levels of 247 +/- 11 pmol/l and 586 +/- 59 pmol/l, respectively (p less than 0.001). In conclusion, although the glucose tolerance is impaired and plasma insulin responses to intravenous glucose-load and test-meal are reduced, the alginate-polylysine membrane does provide adequate immunoisolation for the prolongation of allograft survival, resulting in prolonged normoglycaemia in streptozotocin diabetic rats. PMID- 1936657 TI - Studies on autoimmunity for initiation of beta-cell destruction. VIII. Pancreatic beta-cell dependent autoantibody to a 38 kilodalton protein precedes the clinical onset of diabetes in BB rats. AB - Autoantibody to a rat islet cell-protein of 38 kilodalton was detectable at around 30 days of age in the sera of diabetes-prone Biobreeding (DP-BB) rats by both immunoprecipitation and differential Western blotting methods. Anti-38 kilodalton islet cell autoantibody was not, however, observed in the sera from 5- to 20-day-old DP-BB rats. Over 90% of DP-BB rats in which the antibody was detected, eventually developed Type 1 (insulin-dependent) diabetes mellitus. The antibody disappeared within 2 weeks after diabetes onset. However, it was preserved in the sera of DP-BB rats which had been treated with silica to prevent insulitis. The anti-38 kilodalton islet cell autoantibody was not detected in sera from control Wistar Furth (WF) rats. The autoantibody also cross-reacted with a rat insulinoma (RINm5F) cell protein of 38 kilodalton, but did not react with protein from mouse fibroblast (L-929 cells), rat pituitary cells (GH3 cells), or normal rat lymphocytes. The production of the autoantibody appears to be pancreatic Beta-cell dependent, since the autoantibody disappears after almost complete depletion of Beta cells, but is consistently present as long as Beta cells remain. Identification of the Beta-cell dependent anti-38 kilodalton islet cell autoantibody, which cross-reacts with a rat insulinoma cell protein of 38 kilodalton and precedes the onset of Type 1 diabetes in BB rats, will be invaluable for study of the molecular nature of a target islet cell autoantigen associated with the induction of autoimmunity in DP-BB rats. PMID- 1936658 TI - Increased insulin action in the rat after protein malnutrition early in life. AB - The effect of a limited period of low protein feeding in young rats on insulin secretion and insulin action during adult-age has been studied. Four-week-old rats were maintained for 4 weeks on isocaloric diets containing 5% protein (low protein) or 15% protein (control). The low protein rats gained weight at a considerably lower rate than the control rats. This was obtained in the absence of any decrease of spontaneous food intake. Basal plasma insulin levels were decreased (p less than 0.01) by 40% in low protein rats. However, the glucose stimulated insulin secretion obtained in vivo after an i.v. glucose load remained normal. The basal plasma glucose level in the low protein rats was only marginally decreased (by 20%). The tolerance to i.v. glucose was found to be slightly enhanced in the low protein rats as compared to the control rats as shown by a significantly increased K value (p less than 0.01). In vivo insulin action in the low protein rats was investigated using the euglycaemic hyperinsulinaemic clamp technique in conjunction with isotopic measurements of glucose turnover. The overall glucose utilization rate was normal in the basal state but significantly increased (p less than 0.05) when measured at a submaximal plasma insulin level. The basal hepatic glucose production in the low protein rats was similar to that in the control rats. During the clamp studies, the suppression of endogenous glucose production was found to be similar in the low protein rats and the control rats but this was obtained at significantly lower (p less than 0.01) steady-state insulin levels in the low protein group than in the control group. In conclusion, the current results indicate that the modest improvement of glucose tolerance which is revealed in the low protein rats results from changes in the insulin action upon the target tissues: both the insulin-mediated glucose uptake by peripheral tissues and the ability of insulin to suppress hepatic glucose output are enhanced. PMID- 1936659 TI - Evaluation of inhibitory guanine nucleotide regulatory protein Gi function in hepatocyte and liver membranes from obese Zucker (fa/fa) rats and their lean (Fa/?) littermates. AB - Previous studies have shown that hepatocyte and liver membranes from insulin resistant animals exhibit an impairment of inhibitory guanine nucleotide binding regulatory protein, Gi function, such that a Gi defect may contribute towards the diabetic syndrome. In the current studies, it is shown that the demonstration of Gi activity in liver and hepatocyte membranes is dependent critically on the membrane preparation technique. A technique is defined that allows functional Gi activity to be demonstrated in liver and hepatocyte membranes from both lean (Fa/?) and obese (fa/fa) Zucker rats. Consequently, previous reports on the loss of Gi function in insulin resistant states require revaluation. PMID- 1936660 TI - No glucotoxicity after 53 hours of 6.0 mmol/l hyperglycaemia in normal man. AB - In vitro and in vivo studies have suggested that metabolic deterioration can be induced by hyperglycaemia per se. The effect of 53 h of 2.2 mg glucose.kg ideal body weight-1.min-1 was examined in four normal male subjects. This produced overnight hyperglycaemia of 6.0 mmol/l on the two nights of the study compared with 4.7 mmol/l on the control night (p less than 0.05). In response there was a sustained, two-fold increase in basal plasma insulin (p less than 0.005) and C peptide (p less than 0.05) levels. After two days of hyperglycaemia an increased Beta-cell response was demonstrated in response to an additional glucose infusion stimulus (estimated Beta-cell function median of 84% on the control day to 100% after two days glucose infusion). Plasma insulin and C-peptide responses to a 10.0 mmol/l hyperglycaemic clamp increased over the two days of the study (insulin from median 48 mU/l to 73 mU/l and C-peptide from median 2.0 pmol/ml to 2.6 pmol/l). Glucose tolerance to the additional glucose infusion stimulus improved, suggesting that the increased insulin response during hyperglycaemia was enhancing peripheral glucose uptake. The calculated peripheral insulin sensitivity was unchanged during the hyperglycaemic clamp. Thus, in response to the two days of basal hyperglycaemia, both the basal and stimulated Beta-cell responses were enhanced and there was no evidence for 'glucose toxicity' to the Beta-cells. PMID- 1936661 TI - The Swedish childhood diabetes study: indications of severe psychological stress as a risk factor for type 1 (insulin-dependent) diabetes mellitus in childhood. AB - This study is part of a nationwide case-referent study. All recent-onset Type 1 (insulin-dependent) diabetic children aged 0-14 years in Sweden were invited to participate. Referent subjects matched for age-, sex- and geographical distribution were selected. In all, 338 patients and 528 referent subjects took part. Life events during the last year prior to clinical onset of Type 1 diabetes were recorded on a questionnaire. The total frequency of life events did not differ between diabetic and referent children. However, qualitatively the life events reported by diabetic children revealed a tendency to increased severity. Events related specifically to actual or threatened losses within the family- events that may affect children differently in different age groups--were reported with a significantly higher frequency by diabetic patients than by referent subjects, aged 5-9 years. The relative risk that such events in fact comprise a risk factor for Type 1 diabetes was 1.82 (95% confidence limits 1.09, 3.03). The relative risk was significantly increased even when standardized for possible confounding factors such as age, sex and indices of social status of the family. We conclude that stressful life events, related to actual or threatened losses within the family, occurring in the vulnerable age group of 5-9 years, are associated with the onset of childhood Type 1 diabetes. Such stressful events may in fact be a risk factor for the disease. PMID- 1936662 TI - Incidence of macrovascular disease in diabetes mellitus: the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics. AB - We report on the incidence of new macrovascular disease among the 497 members of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35-54 years at recruitment) over a mean 8.33 year follow-up period. Overall at the end of the follow-up period the prevalence of macrovascular disease in the cohort was 45%; 43% of the subjects showed evidence of ischaemic heart disease, 4.5% of cerebrovascular disease and 4.2% of peripheral vascular disease. The incidence rates for new disease in those subjects who were free at baseline expressed per 1000 patient years of follow-up were: ischaemic ECG abnormality 23.6 (patients with insulin-dependent diabetes 19.8, patients with non-insulin dependent diabetes 28.1), myocardial infarction 17.6 (patients with insulin dependent diabetes 16.5, patients with non-insulin-dependent diabetes 18.8), all ichaemic heart disease 31.7 (patients with insulin-dependent diabetes 30.3, patients with non-insulin-dependent diabetes 33.4), cerebrovascular disease 5.9 and peripheral vascular disease 5.2. Incidence rates were generally similar among men and women except for myocardial infarction in patients with non-insulin dependent diabetes where men had a significantly higher incidence rate. Macrovascular disease is a major problem in patients with diabetes and in this age group is mainly manifested as ischaemic heart disease. PMID- 1936663 TI - Risk factors for macrovascular disease in diabetes mellitus: the London follow-up to the WHO Multinational Study of Vascular Disease in Diabetics. AB - We have examined the relationship between baseline variables and the incidence of new macrovascular complications amongst the 497 members of the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics over a mean 8.33 year follow-up. In univariate logistic regression analysis the incidence of new ischaemic electrocardiographic abnormality was significantly associated with systolic and diastolic blood pressure, diabetes duration and hypertension in patients with insulin-dependent diabetes, and with smoking in patients with non insulin-dependent diabetes. New myocardial infarction was associated with systolic blood pressure, plasma cholesterol, proteinuria and smoking in patient with non-insulin-dependent diabetes; there were no significant associations among patients with insulin-dependent diabetes. All new ischaemic heart disease was associated with hypertension in patients with insulin-dependent diabetes, and plasma cholesterol and smoking in patients with non-insulin-dependent diabetes. New cerebrovascular disease was associated with systolic and diastolic blood pressure, ECG abnormality and hypertension. New peripheral vascular disease was associated with smoking. Multivariate analysis showed the following significant associations 1) in patients with insulin-dependent diabetes: ECG abnormality; hypertension, myocardial infarction; smoking, ischaemic heart disease; hypertension, diabetes duration and smoking, 2) in patients with non-insulin dependent diabetes: ECG abnormality; smoking, myocardial infarction; serum cholesterol, proteinuria and smoking ischaemic heart disease; smoking. For new cerebrovascular disease, proteinuria and ECG abnormality were significant predictors in multivariate analysis. Patients with diabetes share many of the established risk factors for nondiabetic subjects, in addition proteinuria may be of significance in the prediction of macrovascular disease in diabetes. PMID- 1936664 TI - Impaired response to angiotensin II in type 1 (insulin-dependent) diabetes mellitus. Role of prostaglandins and sodium-lithium countertransport activity. AB - The pathogenesis of diabetic nephropathy remains elusive. A role for renal prostaglandins in antagonizing the hormonal effects of renin-angiotensin II has been postulated as a putative factor leading to hyperfiltration in patients with Type 1 (insulin-dependent) diabetes mellitus. Our aim was to elucidate the effects of angiotensin II on kidney haemodynamics and on blood pressure in eight normal subjects, in nine normotensive, in nine hypertensive with normal sodium lithium countertransport activity in erythrocytes, in seven hypertensive without and in eight hypertensive Type 1 diabetic patients with microalbuminuria and with high sodium-lithium countertransport activity in erythrocytes. Angiotensin II infusion (4 ng.kg-1.min-1 for 60 min) decreased the glomerular filtration rate to a greater extent in normal subjects (-20%), than in normotensive patients (-5% p less than 0.01), in hypertensive patients with normal sodium-lithium countertransport activity in erythrocytes (-8% p less than 0.01) in hypertensive patients with high sodium-lithium countertransport (-6% p less than 0.01) and in hypertensive microalbuminuric patients (-5% p less than 0.01) with Type 1 diabetes. The urinary excretion rate of vasodilatory prostaglandins was two-three fold higher in all patients than in normal subjects. Acute indomethacin treatment restored a normal response to angiotensin II infusion in normotensive patients, but did not change the renal haemodynamic response in normal subjects. With regard to hypertensive patients with and without microalbuminuria indomethacin treatment restored a normal response to angiotensin II in some but not all patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936666 TI - Follow-up of glomerular hyperfiltration in normoalbuminuric type 1 (insulin dependent) diabetic patients. PMID- 1936667 TI - Secondary complications and quality of life after successful pancreatic transplantation in type 1 (insulin-dependent) diabetes mellitus. 3d Spitzingsee meeting. Kuhtai, Austria, 6-9 January 1991. Proceedings. PMID- 1936665 TI - Is muscle the major site of insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus? PMID- 1936668 TI - Outcome of pancreas transplantations in Goteborg, Sweden 1985-1990. AB - During 1985 to 1990, 67 segmental pancreas transplantations with bladder drainage were performed. Fifty were combined pancreas and kidney and 17 were pancreas after kidney transplants. All patients were transplanted with the same technique. The 1-year actuarial pancreas graft survival for the combined patients with quadruple immunosuppressive therapy was 83% and the patient survival, 95%. The most important complications were infections, leakage from the pancreatico cystostoma and vascular complications. PMID- 1936669 TI - Sequential electrodiagnostic evaluation of diabetic neuropathy after combined pancreatic and renal transplantation. AB - To assess the long-term evolution of diabetic polyneuropathy after a combined kidney-pancreas transplant, an electrophysiological study was performed in 20 diabetic patients before transplant, and 1 (n = 18), 2 (n = 16), 3 (n = 10) and 4 years (n = 5) at a later date. Motor and sensory scores were calculated for conduction velocity and amplitude to determine the physiopathological process. During evolution the scores were not found to be decreasing. Motor and sensory velocity scores were significantly improved (p less than 0.05) 1 and 2 years after the graft, when score values tended to stabilize. Motor and sensory amplitude scores, which are more sensitive for axonal loss assessment were slightly but not significantly improved. PMID- 1936670 TI - Neurophysiological study of the effect of combined kidney and pancreas transplantation on diabetic neuropathy: a 2-year follow-up evaluation. AB - Previous study have reported a significant improvement of peripheral neuropathy following combined pancreas and kidney transplantation attributed to improvement of blood glucose control by some authors and to elimination of uraemia by others. To asses the specific role of uraemia and hyperglycaemia in neuropathy, 16 diabetic uraemic patients with combined pancreas and kidney transplantation were compared to 9 diabetic patients with a renal graft only. Neurophysiological studies of peripheral neuropathy included ulnar and deep peroneal nerve motor conduction velocity, median and sural nerve sensory conduction velocity were performed at baseline and 1 and 2 years after transplantation. One year after transplantation mean nerve conduction velocity significantly improved in both groups. However, changes were statistically significant in the kidney-pancreas group only. At the 2 year follow-up nerve conduction velocity had increased further in the pancreas-kidney group only. These data suggest that improvement of nerve conduction velocity following pancreas and kidney transplantation is predominantly due to the long-term euglycaemic state. PMID- 1936671 TI - Autonomic neuropathy and survival in diabetes mellitus: effects of pancreas transplantation. AB - Cardiorespiratory reflexes were studied during slow breathing and a Valsalva maneuver in 232 Type 1 (insulin-dependent) diabetic subjects. At 1 to 7 years follow-up, death occurred in 23.4% of 175 patients with abnormal reflexes and in 3.5% of 57 patients with normal reflexes. The mortality rates of diabetic subjects with abnormal reflexes were 17% at 2.5 years, 33% at 5 years and 40% at 7 years, significantly higher than for patients with normal reflexes (4.6%, 4.6% and 13.8%). Among patients with abnormal reflexes, patients with a functioning pancreas transplantation had better survival rates than patients with a failed transplantation, and in long-term follow-up better than patients without transplantation. A functioning transplantation prevented the progressive decline of cardiorespiratory reflex function that occurred over time in control patients. PMID- 1936672 TI - Pancreas and kidney transplantation: the San Raffaele Hospital (Milan, Italy) experience. AB - Results of 33 simultaneous pancreas and kidney transplantations performed at the San Raffaele Hospital, Milan, Italy are presented. In 26 cases segmental neoprene duct-injected grafts were transplanted and in seven cases, duodenopancreatic bladder-drained grafts. Five-year patient, kidney and pancreas survival were respectively, 89%, 72% and 58%. Five-year survival in patients with technically successful pancreas transplants was 73%. Thrombosis occurred in 20% of cases. Mortality was 6% and overall morbidity 76%. Surgical complications were present in 51% of cases. PMID- 1936673 TI - Follow-up study of sensory-motor polyneuropathy in type 1 (insulin-dependent) diabetic subjects after simultaneous pancreas and kidney transplantation and after graft rejection. AB - The influence of successful simultaneous pancreas and kidney transplantation on peripheral polyneuropathy was investigated in 53 patients for a mean observation period of 40.3 months. Seventeen patients were followed-up for more than 3 years. Symptoms and signs were assessed every 6 months using a standard questionnaire, neurological examination and measurement of sensory and motor nerve conduction velocities. While symptoms of polyneuropathy improved (pain, paraesthesia, cramps, restless-legs) and nerve conduction velocity increased, there was no change of clinical signs (sensation, muscle-force, tendon-reflexes). Following kidney-graft-rejection there was a slight decrease of nerve conduction velocity during the first year, which was not statistically significant. Following pancreas-graft rejection there was no change of nerve conduction velocity during the first year. Comparing the maximum nerve conduction velocity of the patients with pancreas-graft-rejection to the nerve conduction velocities of these patients at the end of the study, there was a statistically significant decrease of 6.5 m/s. In conclusion, we believe that strict normalization of glucose metabolism alters the progressive course of diabetic polyneuropathy. It may be stabilized or partly reversed after successful grafting even in long-term diabetic patients. PMID- 1936674 TI - Effect of pancreatic and/or renal transplantation on diabetic autonomic neuropathy. AB - Thirty-nine Type 1 (insulin-dependent) diabetic patients were studied prospectively after simultaneous pancreas and kidney (n = 26) and kidney grafting alone (n = 13) by measuring heart rate variation during various maneuvers and answering a standardized questionnaire every 6 to 12 months post-transplant. While age, duration of diabetes, and serum creatinine (168.1 +/- 35.4 vs 132.7 +/ 17.7 mumol/l) were comparable, haemoglobin A1 levels were significantly lower (6.6 +/- 0.2 vs 8.5 +/- 0.3%; p less than 0.01) and the mean observation time longer (35 +/- 2 vs 25 +/- 3 months; p less than 0.05) in the pancreas recipients when compared with kidney transplanted patients. Heart rate variation during deep breathing, lying/standing and Valsalva manoeuver were very similar in both groups initially and did not improve during follow-up. However, there was a significant reduction in heart rate in the pancreas recipient group. Autonomic symptoms of the gastrointestinal and thermoregulatory system improved more in the pancreas grafted subjects, while hypoglycaemia unawareness deteriorated in the kidney recipients. This study suggests that long-term normoglycaemia by successful pancreatic grafting is able to halt the progression of autonomic dysfunction. PMID- 1936675 TI - Diabetic autonomic neuropathy after pancreas and kidney transplantation. AB - We have evaluated the effect of successful pancreatic and kidney transplantation on autonomic neuropathy in nine Type 1 (insulin-dependent) diabetic subjects. Cardiovascular reflex tests were performed before and at 6-24 months after transplantation. A control group of ten Type 1 diabetic patients after kidney grafting only was examined at the same time periods. For base-line comparisons results of the tests in ten healthy subjects were used. Advanced autonomic neuropathy was present in both groups of transplant recipients and no significant changes in test results could be found at post-transplant evaluation. Lack of autonomic nerve function improvement was confirmed in seven patients of the pancreatic and kidney transplantation group who were examined again after 2-4 years. Irreversible structural autonomic nerve damage is probably present in uraemic pancreatic transplantation candidates. PMID- 1936676 TI - Improvement in diabetic neuropathy 4 years after successful pancreatic and renal transplantation. AB - We have studied the fate of diabetic neuropathy and autonomic function in 13 patients with long standing Type 1 (insulin-dependent) diabetes mellitus following combined pancreas and kidney transplantation. Fifteen diabetic patients with a kidney graft only served as controls. After initial improvement of the neuropathy in both groups, probably caused by the elimination of uraemia, a continuous improvement during the 48 months study was seen in the euglycaemic pancreas graft recipients only. Autonomic (parasympathetic) function improved only slightly and to a similar extent in both groups. PMID- 1936677 TI - Echocardiographic findings in kidney transplanted type 1 (insulin-dependent) diabetic patients with and without a pancreas transplant. AB - Echocardiography with Doppler recordings was carried out in 14 Type 1 (insulin dependent) diabetic recipients of pancreas and kidney transplants and in 14 Type 1 diabetic kidney transplanted control patients, matched for age, sex, duration of diabetes, extent of other late complications, time since transplantation, dose of prednisolone, and renal function. HbA1c was 5.5 +/- 0.6 vs 8.7 +/- 1.4% (pancreas transplanted vs kidney only). Both groups had a slight increase in interventricular septum thickness. Left ventricular mass was equal. The ejection fraction as a measure of systolic function was normal and equal, 0.71 +/- 0.05 vs 0.69 +/- 0.07. Diastolic function was also equal in two out of three parameters, isovolumic relaxation time and deceleration time. The A/E ratio, however, tended to be lower in the pancreas transplanted group, 0.94 +/- 0.20 vs 1.06 +/- 0.18 (p = 0.04). This indicates more frequent occurrence of impaired diastolic filling in the recipients of kidney only. Follow-up will show whether diastolic dysfunction increases and may be related to the increased cardiovascular mortality in kidney transplanted Type 1 diabetic patients. PMID- 1936678 TI - Diabetic microangiopathy in type 1 (insulin-dependent) diabetic patients after successful pancreatic and kidney or solitary kidney transplantation. AB - To evaluate the beneficial effect of pancreatic grafting on peripheral microcirculation and long-term clinical outcome, we compared data of 28 Type 1 (insulin-dependent) diabetic patients either given a pancreatic and kidney graft simultaneously or given a solitary kidney graft (n = 17). Peripheral microcirculation was estimated by transcutaneous oxygen pressure measurement (including reoxygenation potential after blood flow occlusion) and erythrocyte flow/velocity by a non-contact laser speckle method. All the measured parameters showed significant differences between diabetic and control subjects in the mean follow-up time of 49 (simultaneous pancreas and kidney transplantation) and 43 (solitary kidney transplantation) months. The data from patients after simultaneous pancreas and kidney transplantation revealed an improvement of transcutaneous oxygen pressure measurement (rise from 46 +/- 2 mm Hg to 63 +/- 3 mmHg), reoxygenation time (fall from 224 +/- 12s to 114 +/- 6s) and laser speckle measurement (rise from 4.2 +/- 1.7 to 5.6 +/- 1.8 relative units). The control group with solitary kidney transplantation did not show a positive evaluation. Data from patients after simultaneous pancreas and kidney transplantation revealed an improvement in transcutaneous oxygen pressure measurement, reoxygenation time and laser speckle measurement whereas the control group with solitary kidney transplantation did not show a positive evaluation. Improved microcirculation was more pronounced in patients with better microvascular preconditions. The results confirm that diabetic microangiopathy is positively influenced by pancreatic transplantation. PMID- 1936680 TI - Pancreas transplantation: assessing secondary complications and life quality. AB - Two sequential studies of life quality among pancreas transplant recipients are reported. The first study (n = 32) investigated symptoms of neuropathy, enteropathy and retinopathy, along with well-being post successful transplantation. Patients noted improvement in secondary complications, were satisfied with the procedure and expressed hope for the future. The second study compared physical and social function, burden of symptoms, emotional/mental state and sense of well-being in successful (n = 31) and successful (n = 13) pancreas transplant recipients. Patient satisfaction with pancreas transplantation was high. Successful transplant patients perceived their health to be good, believed it would continue to be good, with life quality becoming better over time. The failed group expected life quality to become worse. PMID- 1936679 TI - Skin microvascular reactivity in fingers of diabetic patients after combined kidney and pancreas transplantation. AB - Nine patients with severe late diabetic complications were investigated 2 and 38 months after successful combined kidney and pancreas transplantation. Nine healthy subjects served as controls. Blood cell velocity in single capillaries was evaluated by videophotometric capillaroscopy, and total skin microcirculation of the same area by laser Doppler fluxmetry. The measurements were performed during rest, and post-occlusive (1 min) reactive hyperaemia. Laser Doppler flux was also recorded during venous occlusion. The basal capillary blood cell velocity and laser Doppler flux values increased significantly (p less than 0.05) during the observation period. The time to maximal capillary blood cell velocity during hyperaemia was prolonged 2 months after combined kidney and pancreas transplantation (p less than 0.05), and still more so at 38 months (p less than 0.05). The ability to decrease blood flow during venous occlusion was impaired at 2 months, and was not significantly better at reinvestigation. The results indicate a succesive increase of basal blood flow in the skin microcirculation after successful combined kidney and pancreas transplantation, but no improvement of the impaired microvascular reactivity. PMID- 1936681 TI - Long-term results in pancreatic transplantation with special emphasis on the use of prolamine. AB - Our pancreatic transplantation programme was initiated in 1979. Since then a total of 102 pancreas transplantations have been performed, blocking exocrine secretion using the duct occlusion technique with prolamine. Early non immunological complications are frequent. The long-term results (9 years) in combined pancreas and kidney transplanted patients are satisfying: the survival rate for pancreas is 38% and 54% for kidney. Patient survival rate in this period is 85%. Beyond the first year post-transplant the exocrine activity disappears whereas the endocrine function remains well preserved. PMID- 1936682 TI - Effect of pancreas transplantation on life expectancy, kidney function and quality of life in uraemic type 1 (insulin-dependent) diabetic patients. AB - The aim of our study was to evaluate the effects of haemodialysis, kidney transplantation and simultaneous kidney and pancreas transplantation on survival of diabetic subjects and on kidney function. 40 Type 1 (insulin-dependent) diabetic patients received a kidney transplantation: in 31 cases the kidney was transplanted simultaneously to a pancreas graft from the same donor (KP group), while in 9 cases the pancreas was not available (K group). 44 uraemic Type 1 (insulin-dependent) diabetic patients on dialysis and in waiting list for kidney transplantation, constituted the control group (HD group). Patient survival rate 1, 3 and 5 years following transplantation was better in KP group (93%, 89%, 89%, respectively) and in K group (88%, 88%, 73%, respectively) and in HD group (88%, 62%, 51%, respectively). Kidney graft survival at 1, 3 and 5 years post transplant was better in KP group (93%, 72%, 72%, respectively) than in K group (76%, 61%, 31%, respectively). 1 year after transplantation, patients of the KP group who had lost the pancreas for technical reasons (thrombosis) were included in the K group so as to evaluate the effect of the transplanted pancreas on long term patient and kidney survival. Patient survival rate in the KP group (17 patients) at 2 and 4 years was 100%, while at the same intervals it was 78% in the K group (13 patients). Kidney graft function rate at 2 and 4 years was 93% in the KP group (17 grafts) and 54% and 27% respectively in the K group (14 grafts).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936683 TI - Quality of life of pancreas transplant recipients. AB - The quality of life outcome of 131 pancreas transplant recipients who were 1 to 11 years post-transplant were studied. Patients with a functioning pancreas graft (n = 65) described their current quality of life and rated their health significantly more favourably than those with non-functioning grafts (n = 66). For example, of those patients with a functioning pancreas graft, 68% expressed overall satisfaction with their life, 89% felt healthier since their transplant, and 78% reported that they could care for themselves and their routine daily activities. In contrast, of those patients without a functioning graft, only 48% expressed overall satisfaction with life (p less than 0.01), only 25% felt healthier since their transplant (p less than 0.001), and only 56% indicated they could care for themselves and their daily activities (p less than 0.001). Regardless of graft function, the majority of patients were comfortable with their decision to have the transplant, and most of the patients with pancreas graft function reported that they would have another transplant if their graft failed. While successful pancreas transplantation may not elevate all diabetic patients to the level of health and function of the general population, these patients report a significantly better quality of life than do those patients who remain diabetic. PMID- 1936684 TI - Quality of life in type 1 (insulin-dependent) diabetic patients prior to and after pancreas and kidney transplantation in relation to organ function. AB - Improvement of the quality of life in Type 1 (insulin-dependent) diabetic patients with severe late complications is one of the main goals of pancreas and/or kidney grafting. To assess the influences of these treatment modalities on the different aspects of the quality of life a cross-sectional study in 157 patients was conducted. They were categorized into patients pretransplant without dialysis (n = 29; Group A), pretransplant under dialysis (n = 44; Group B), posttransplant with pancreas and kidney functioning (n = 31; Group C), post transplant with functioning kidney, but insulin therapy (n = 29; Group D), post transplant under dialysis and insulin therapy again (n = 15; Group E) and patients after single pancreas transplantation and rejection, with good renal function, but insulin therapy (n = 9; Group F). All patients answered a mailed, self-administered questionnaire (217 questions) consisting of a broad spectrum of rehabilitation criteria. The results indicate a better quality of life in Groups C and D as compared to the other groups. In general the scores are highest in C, but without any significant difference to D. Impressive significant differences between C or D and the other groups were found especially in their satisfaction with physical capacity, leisure-time activities or the overall quality of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936685 TI - Rehabilitation and quality of life in diabetic patients after successful pancreas kidney transplantation. AB - Twenty-seven Type I diabetic patients in end-stage renal failure were followed after combined pancreas-kidney transplantation. All patients received duct occluded segmental pancreas grafts. Clinical progression of extrarenal diabetic complications was studied in 11 patients with long-term functioning pancreatic and renal transplants (Group 1), and in 16 patients who had lost pancreatic graft function, but retained renal graft function (Group 2). Pretransplant, extrarenal diabetic complications were equally distributed in the two groups. In the follow up period, however, the progress of these complications was less severe in patients with functioning pancreatic transplants. No differences were found between the groups concerning rehabilitation, working capacity, need of help or hospital admittance. It is suggested that pancreas transplantation performed in an earlier stage of diabetes before serious complications have developed, would probably improve rehabilitation and quality of life in these patients. PMID- 1936686 TI - Outcome of renal grafts after simultaneous kidney/pancreas transplantation. AB - Nineteen patients with endstage renal failure due to Type 1 (insulin-dependent) diabetes mellitus received simultaneous pancreas/kidney transplants using bladder drainage technique. Another group of 25 Type 1 diabetic patients received pancreas/kidney transplants by the duct occlusion technique. We observed a higher incidence of rejection episodes in the patients of the bladder drainage group than those in the duct occlusion group, 14 of 19 patients (74%) vs 7 of 25 (28%) respectively. Anti CD3 antibodies (OrthocloneR, OKT3) as a part of induction treatment was used more often in the bladder drainage group (58%) than in the control group (20%). PMID- 1936687 TI - Indications and results of pancreatic transplantation: the Oslo experience 1983 1990. AB - The Norwegian pancreas transplantation programme was initiated in June 1983. By November 1990, a total of 77 pancreatic transplantations had been performed, 63 simultaneously with a renal transplant. Five patients received pancreatic grafts after previous renal grafting while nine non-uraemic diabetic patients received pancreatic grafts only. In April 1988, the surgical technique was changed from duct-occluded segmental pancreas to whole pancreas grafting with duodenocystostomy. In recipients of combined grafts from the first group (segmental pancreatic grafts), the 1- and 5-year survival rates were 96% and 90% for the patients, 84% and 69% for renal grafts and 66% and 45% for pancreatic grafts. In the second group (whole pancreatic grafts with duodenocystostomy), the 6-month and 2-year survival rates were 87% at both intervals for the patients, 87% and 75% for both grafts. However, even though the bladder drainage technique allows isolated pancreas graft rejection to be diagnosed, the results of isolated pancreas grafting were not improved by this technique, and most of these grafts were lost in therapy-resistant graft rejection. PMID- 1936688 TI - The Stockholm experience with pancreatic transplantation using enteric exocrine diversion. AB - Between April 1974 and June 1990, 128 pancreatic transplantations were performed. Of these 117 were with pancreatico-enterostomy. In four consecutive series of combined transplantations in uraemic diabetic patients the 1-year graft survival rate have successively improved (27%, 65%, 68% and 73%). In three similar series of single pancreatic transplantations the results also improved but still remained inferior (0%, 33% and 33%). In a series of combined transplantations performed in preuraemic diabetic patients the 1-year actuarial graft survival rate was only 25%. The results with pancreatic transplantation with pancreatico enterostomy are now satisfactory. However, immunological loss graft function still constitute a major problem in the non- or pre-uraemic recipients. The metabolic control in patients with functioning grafts is normal or near-normal in the majority of patients followed for at least 1 year. PMID- 1936689 TI - The bladder drainage technique in pancreas transplantation--the Tubingen experience. AB - Starting in 1987 renal- and pancreaticoduodenal--transplantations were performed simultaneously in a consecutive series of 40 patients with Type 1 diabetes mellitus and end-stage renal disease. Exocrine secretion of the pancreatic graft does not seem to be a crucial problem anymore when using the bladder drainage technique. No pancreatic fistulae were seen. No graft lost its function due to early post-operative graft thrombosis. Early post-operative graft pancreatitis and recurrent urinary tract infections remain the drawbacks of the bladder drainage technique. Despite a strong immunestimulation of the recipient by the combined pancreaticoduodenal/renal allograft all but two rejection episodes could be reversed by using different monoclonal/polyclonal antibodies. Actuarial 1-year graft survival rate reaches 85% for the pancreas as well as the kidney. Thus, simultaneous pancreas-kidney transplantation can be performed with a high success rate when using the technique described. PMID- 1936690 TI - Report from the International Pancreas Transplant Registry. AB - From December, 1966 through 1990, 3082 pancreas transplants were reported to the International Registry. A detailed analysis was performed on the 2087 transplants in the 1986-90 data base; during this time the overall one year recipient and graft functional survival rates were 89% and 62%. Univariate analyses showed graft survival rates to be significantly higher with bladder drainage than with other duct management techniques, with a simultaneous kidney transplant than without, and with preservation in UW than other solutions. Storage up to 30 hours did not adversely effect results. Graft survival rates were significantly higher in North America than Europe, a discrepancy that persisted in a Cox proportional hazard analysis that also included duct management, recipient category, HLA-DR mismatching, immunosuppression with anti-T cell agents, preservation solution and duration, and year of transplant as the other variables; three were identified to have a significant (p less than 0.05) impact on the relative risk (RR) of graft loss: 1) Recipient category, with an RR of 0.43 when placed simultaneously with a kidney; 2) Year, with an RR of 0.76 for transplants performed in 1989-90 versus 1986-88; and 3) Location, with an RR of 0.75 for transplants in North America versus Europe. The technical failure rate was significantly lower in North America than Europe, but this was not an explanation for the differences in outcome, since the same factors sorted out as significant in a Cox proportional hazard analysis of technically successful cases only. Furthermore, logistic regression analysis showed retransplantation, duct management, recipient category, preservation solution, and storage time to significantly influence the technical failure rate. The risk of technical failure was lowest for primary, bladder-drained, simultaneous pancreas/kidney, less than 12 hour UW stored grafts; year and location of transplant were not significant factors. Pancreas transplant results continue to improve and are in the range of those for other solid organs. PMID- 1936691 TI - Pancreatic transplantation with delayed duct occlusion versus bladder drainage: long-term results. AB - Between April 1985 and August 1990 a total of 51 combined pancreas kidney transplants and 6 single pancreas transplants were performed in 51 Type 1 (insulin - dependent) diabetic patients suffering from end-stage diabetic nephropathy and three patients with proliferative retinopathy. In 17 transplants the pancreatic duct was occluded with a mean delay of 53 days (Group 1). Because of a high incidence of local complications associated with a prolonged hospitalization this technique was abandoned despite favourable results: The actual survival rates for patients, pancreas and renal allografts at 1 year are 94%, 72% and 93%, respectively. From 1987 a total of 39 consecutive segmental pancreas grafts were anastomosed with the urinary bladder (Group 2). Pancreatic secretions were temporarily drained to the exterior in all patients via a duct catheter. Monitoring of the exocrine function including pancreatic secretion cytology and pancreatic secretion neopterin excretion proved to be reliable rejection markers. Survival rates at 1 year were calculated to be 90%, 74% and 89% for all patients, pancreas grafts and renal grafts. Apart from local complications in group I which did not cause any graft loss, the surgical complication rate was comparably low in both groups. PMID- 1936692 TI - Metabolic characteristics in patients with long-term pancreas graft with systemic or portal venous drainage. AB - Between January 1983 and June 1990, 32 simultaneous pancreas and kidney transplantations were performed at the University of Barcelona. Insulin-secretion was assessed by intravenous glucose tolerance test performed 24h after transplantation and oral glucose tolerance test during the follow-up. Insulin secretion was also studied in seven non-diabetic patients with kidney transplants. Insulin levels in patients with pancreas and kidney transplantations both at the basal level and after glucose stimulation were higher than normal but not different than those observed in patients with kidney transplantation only. Patients with both pancreas and kidney transplantations and kidney transplantation only presented a mild insulin resistance, measured by the glucose/insulin ratio. Insulin levels during the follow-up of a patient with portal venous drainage were similar to those observed in patients with systemic venous drainage. In conclusion, pancreas transplantation allows a long-term maintenance of glucose homeostasis, although coexisting with an insulin resistance, probably related of the immunosuppressive therapy. PMID- 1936693 TI - Metabolic risk factors for cardiovascular disease in pancreas and kidney transplant recipients. AB - Hyperinsulinaemia when combined with insulin resistance and hypertriglyceridaemia is a risk factor for cardiovascular disease. We have studied the serum lipid profile and glycaemic control in 27 uraemic diabetic patients, 23 Type 1 (insulin dependent) diabetic kidney recipients, 18 non-diabetic kidney recipients, and 30 recipients of kidney and pancreas transplants at 6 months post-transplantation. Fasting serum triglycerides were increased in the uraemic diabetic patients and nondiabetic kidney transplanted patients but not in diabetic kidney transplanted patients whether or not they had received a pancreas. Total cholesterol was increased only in the uraemic diabetic patients while HDL cholesterol was normal in all groups. Within the pancreas and kidney transplanted group triglyceride values correlated with glomerular filtration rate (r = -0.55) but not with plasma insulin, glycated haemoglobin or kG-value following an intravenous glucose load. Plasma insulin was increased. Whether such isolated hyperinsulinaemia confers an increased risk of cardiovascular disease is not known. There may be adaptive feed back mechanisms to protect target cells. Increasing the surgical risk in attempts to secure insulin delivery to the portal circulation does not seem warranted. PMID- 1936695 TI - Metabolic control after kidney and pancreas transplantation: whole series results and effects of segmental duct obstruction versus whole pancreas with bladder diversion technique. AB - From October 1976 to December 1990 181 pancreatic transplants were performed in our centre on 171 Type 1 (insulin-dependent) diabetic patients. Oral glucose tolerance test evaluated 1 year after surgery in 31 subjects showed an impaired glucose tolerance at 120 min (blood glucose 9.5 +/- 0.6 mmol/l). Similar results were obtained in seven patients 3 years after transplantation (blood glucose at 120 min 8.3 +/- 1.08 mmol/l). 24h metabolic profiles performed at the same intervals showed near normal blood glucose levels and good insulin release. Preliminary data concerning a randomized, comparative study between whole pancreas with bladder diversion and segmental pancreas transplantation, showed better metabolic control in the patients who received the whole pancreas, probably due to the greater islet mass grafted. PMID- 1936694 TI - Long-term follow-up of glycaemic control and parameters of lipid transport after pancreas transplantation. AB - We report the long-term metabolic observations made on 37 patients after simultaneous pancreas and kidney transplantation. Plasma C-peptide levels were above the physiological range in all patients and there was no significant difference between patients undergoing delayed duct occlusion (n = 12) or those with drainage of exocrine secretion into the urinary bladder (n = 25). HbA1c was equally at the upper end of the normal range in both subsets of patients. Mean fasting cholesterol (237 mg/dl) and triglycerides (122 mg/dl) were normal, and HDL-cholesterol was above normal with an average concentration of 77 mg/dl. Two patients underwent an oral fat tolerance test and showed extremely low postprandial lipaemia and very high lipoprotein lipase activities. We conclude that patients with a functioning pancreas graft persistently demonstrate normoglycaemia, elevated C-peptide, and a very favourable lipid profile both in the fasting and the postprandial state. PMID- 1936696 TI - First peak insulin release after intravenous glucose and arginine is maintained for up to 3 years after segmental pancreas transplantation. AB - In this study we have investigated blood glucose and serum free insulin response to glucose and to arginine orally or intravenously, 3 months and 3 years after a successful segmental, neoprene-injected, pancreas transplantation. Serum insulin responses to different secretagogues were normal 3 months after transplantation; they remained normal up to 3 years after transplantation. PMID- 1936697 TI - Time-related, cross-sectional and prospective follow-up of pancreatic endocrine function after pancreas allograft transplantation in type 1 (insulin-dependent) diabetic patients. AB - It has been established that successful pancreas transplantation in Type 1 (insulin-dependent) diabetic patients results in normal but exaggerated phasic glucose-induced insulin secretion, normal intravenous glucose disappearance rates, improved glucose recovery from insulin-induced hypoglycaemia, improved glucagon secretion during insulin-induced hypoglycaemia, but no alterations in pancreatic polypeptide responses to hypoglycaemia. However, previous reports have not segregated the data in terms of the length of time following successful transplantation and very little prospective data collected over time in individual patients has been published. This article reports that in general there are no significant differences in the level of improvement when comparing responses as early as three months post-operatively up to as long as two years post-operatively when examining the data cross-sectionally in patients who have successfully maintained their allografts. Moreover, this remarkable constancy in pancreatic islet function is also seen in a smaller group of patients who have been examined prospectively at various intervals post-operatively. It is concluded that successful pancreas transplantation results in remarkable improvements in Alpha and Beta cell but not PP cell function that are maintained for at least one to two years. PMID- 1936698 TI - Metabolic and hormonal studies of type 1 (insulin-dependent) diabetic patients after successful pancreas and kidney transplantation. AB - Long-term normalization of glucose metabolism is necessary to prevent or ameliorate diabetic complications. Although pancreatic grafting is able to restore normal blood glucose and glycated haemoglobin, the degree of normalization of the deranged diabetic metabolism after pancreas transplantation is still questionable. Consequently glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide responses to oral glucose and i.v. arginine were measured in 36 Type 1 (insulin-dependent) diabetic recipients of pancreas and kidney allografts and compared to ten healthy control subjects. Despite normal HbA1 (7.2 +/- 0.2%; normal less than 8%) glucose disposal was normal only in 44% and impaired in 56% of the graft recipients. Normalization of glucose tolerance was achieved at the expense of hyperinsulinaemia in 52% of the subjects. C-peptide and glucagon were normal, while pancreatic polypeptide was significantly higher in the graft recipients. Intravenous glucose tolerance (n = 21) was normal in 67% and borderline in 23%. Biphasic insulin release was seen in patients with normal glucose tolerance. Glucose tolerance did not deteriorate up to 7 years post transplant. In addition, stress hormone release (cortisol, growth hormone, prolactin, glucagon, catecholamines) to insulin-induced hypoglycaemia was examined in 20 graft recipients and compared to eight healthy subjects. Reduced blood glucose decline indicates insulin resistance, but glucose recovery was normal, despite markedly reduced catecholamine and glucagon release. These data demonstrate the effectiveness of pancreatic grafting in normalizing glucose metabolism, although hyperinsulinaemia and deranged counterregulatory hormone response are observed frequently. PMID- 1936699 TI - Long-term metabolic control in recipients of combined pancreas and kidney transplants. AB - Metabolic glucose control was followed in 36 patients at 12-month intervals for up to 5 years after a successful combined kidney and segmental duct-occluded pancreas transplantation. All recipients had normal blood glucose levels at each examination. HbA1 values, intravenous glucose tolerance test, C-peptide levels and C-peptide responses to glucagon stimulation were also, on average, within the normal range. Several individual patients had, however, abnormal values for these parameters. At most 46% had abnormal values for HbA1 and intravenous glucose tolerance test, up to 13% showed low C-peptide values and up to 46% of the stimulated C-peptide responses were inadequate at the different intervals. These parameters did not deteriorate with time. This was true both for the whole group of patients as well as for the 6 patients with a 5-year observation time evaluated separately. Despite these abnormalities in glucose metabolism, all patients remained normoglycaemic without need for exogenous insulin up to 5 years after transplantation. The long-term ability of duct-occluded segmental pancreatic grafts to preserve euglycaemia therefore seems to remain intact at least for 5 years. PMID- 1936700 TI - Insulin action and insulin binding following pancreas transplantation. AB - Insulin action and insulin specific binding to erythrocytes were examined in ten recipients of a pancreatic segment and renal graft (Group 1), in nine non diabetic kidney recipients (Group 2) and in ten age- and weight-matched healthy control subjects (Group 3). All transplant recipients were normoglycaemic without need of insulin, received the same immunosuppression and had good renal graft function at 11-18 months post-transplantation, when the investigation was performed. Using the insulin clamp technique, insulin action was expressed as the metabolic clearance rate of glucose at insulin infusion rates of 1.0 (MCRsubmax) and 10.0 (MCRmax) mU.kg-1.min-1. In comparison with the healthy control subjects, fasting free insulin and C-peptide levels were significantly higher in Groups 1 and 2, but no differences between Groups 1 and 2 were found (p greater than 0.05). Mean values +/- SEM of MCRsubmax in Groups 1, 2 and 3 were 6.30 +/- 0.55, 6.09 +/- 0.69 and 10.52 +/- 1.10 ml.kg-1.min-1 respectively, and of MCRmax 12.65 +/- 0.78, 13.14 +/- 0.92 and 19.28 +/- 1.42 ml.kg-1.min-1 respectively. Insulin action was significantly decreased in Groups 1 and 2 at the low as well as the high insulin infusion rates but there was no difference between the two groups of recipients (p greater than 0.05). No differences in binding data (specific binding, number of binding sites per cell) were found. It is concluded that insulin resistance is common to all immunosuppressed organ recipient and is not related to the pancreas graft. The decrease maximal response to insulin and normal insulin binding to erythrocytes tend to suggest a post-receptor defect in insulin action. PMID- 1936702 TI - Pancreas transplantation in Lyon: overall results. AB - A total of 182 pancreatic transplantations were performed between 1976 and 1990. Survival of the grafts was 45% at 5 years. Major causes of graft loss have been rejection and venous thrombosis. Death occurred in 24 patients and was usually related to vascular complications. The techniques of duodenopancreatic transplantation with enteric drainage, bladder drainage and the technique of segmental duct obstructed grafts were compared. A higher rate of surgical complications was observed with enteric drainage, whereas it is unclear from the data whether segmental grafts or duodenopancreatic grafts drained into the bladder lead to different results. PMID- 1936701 TI - Long-term metabolic control after pancreas transplantation with enteric exocrine diversion. AB - Long-term metabolic control after pancreatic transplantation with enteric exocrine diversion was evaluated in 42 Type I (insulin-dependent) diabetic pancreas recipients with functioning grafts for 1 to 7 years. Glycaemic control (fasting blood glucose, glycosylated haemoglobin A1c, oral and intravenous glucose tolerance tests) was normal or near-normal in most patients, and showed no deterioration with time. In ten patients with functioning grafts for 5 years there was a small, but significant, improvement in the glucose control at 3 to 5 years as compared with that at 6 months post-operatively. In the latter recipients the number of acute rejection episodes correlated negatively with the intravenous glucose tolerance at 6 months (r = -0.64, p less than 0.01) and at 5 years (r = -0.60, p less than 0.01) after transplantation, respectively. The glycaemic control at 6 and 12 months after transplantation was similar whether segmental (n = 35) or whole-organ (n = 7) pancreatic grafts had been used. In six non-uraemic recipients who had received a pancreas transplant alone the serum cholesterol increased in all but one patient (0.05 less than p less than 0.1), and the LDL/HDL-cholesterol ratio was significantly higher (p less than 0.005) one year after transplantation than before. Conversely, in six diabetic patients who had lost the function of their single pancreatic grafts the lipid and lipoprotein profiles remained unaltered. It is concluded that the long-term glycaemic control after segmental or whole-organ pancreatic transplantation with enteric exocrine diversion remains essentially normal in most recipients, and it may even improve with time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936703 TI - Consequences of systemic venous drainage and denervation of heterotopic pancreatic transplants for insulin/C-peptide profiles in the basal state and after oral glucose. AB - Plasma glucose, immunoreactive insulin and C-peptide concentrations were compared in nine pancreas-kidney-transplanted patients (systemic venous drainage) and in ten non-diabetic kidney-transplanted patients with similar kidney function. In the basal state, C-peptide (insulin secretion) was similar, but immunoreactive insulin was higher and glucose concentrations were slightly, but significantly lower in pancrease-transplanted patients. After 50 g oral glucose, the plasma glucose and IR-insulin profiles were similar in both groups. The circumvention of first-pass hepatic insulin extraction (decreased endogenous insulin clearance) was compensated for by a significant reduction in insulin secretion (C-peptide; p = 0.036). In conclusion, hyperinsulinaemia in pancreas-transplanted patients with systemic venous drainage is significant only in the basal state. Insulin delivered into the portal and peripheral circulation, when leading to similar insulin profiles, maintains comparable degrees of glucose tolerance. PMID- 1936704 TI - Does pancreas transplantation influence the course of diabetic retinopathy? AB - Between March 1983 and December 1989 a total of 57 pancreas transplants were performed in 54 patients, of whom 49 also received a kidney for end-stage diabetic nephropathy. Of the surviving 44 patients, 39 had regular pre-operative and post-operative ophthalmological examinations. Diabetic retinopathy was classified according to the original "Early treatment diabetic retinopathy study" (ETDRS) protocol. At the time of this analysis a total of 25 patients had a functioning pancreas transplant and 23 of them also a functioning renal allograft after a mean observation time of 43.2 months (Group 1). They were all free of exogenous insulin, HbA1c being 6.2% (5.1-6.9%; normal value 4.2-5.9%). Fourteen patients in Group 2 lost their pancreas transplant during the first four years. Six of them still have a functioning renal allograft, four patients regularly undergo hemodialysis. Mean HbA1c is 7.5% (5.7-9.2%). Before transplantation, grade of retinopathy according the ETDRS protocol was 6.7 (2-10) in group 1 patients and 7.9 (3-10) in group 2. In group 1 patients stabilisation of retinopathy was observed in 33 eyes (73.3%) and clear improvement achieved in 4 eyes (8.8%). Detoriation occurred in 8 eyes (17.7%) only. In group 2, 14 eyes (54%) remained stable, whereas progression of the disease continued in 12 eyes (46%). From these results it is concluded that the course of diabetic retinopathy is positively influenced by successful pancreas transplantation. PMID- 1936705 TI - Ophthalmological follow-up of type 1 (insulin-dependent) diabetic patients after kidney and pancreas transplantation. AB - We studied the effect of successful kidney and pancreas transplantation on visual function and diabetic retinopathy in 18 patients with long-term Type 1 (insulin dependent) diabetes mellitus (17 to 38 years) and with advanced proliferative retinopathy. The average age of the patients was 42 years. Prior to transplantation, 5 eyes were in end-stage ophthalmic complication due to neovascular glaucoma. An ophthalmological follow-up was performed between 1-6 years post-surgery. Analysis of the results showed that the diabetic retinopathy had stabilized after transplantation in 12 cases (66%) with a supplementary photocoagulation in the majority of cases. The proliferation continued in 4 patients (22%) leading to blindness in 2 patients and recurrence of vitreous haemorrhages despite the photocoagulation in the other 2 cases. An improvement was observed on fluorescein angiography in a patient with pre-papillar glial proliferation without photocoagulation. Ten patients were reported to have a cataract and were operated on in two cases before transplantation; in one patient, the cataract increased following transplantation. In conclusion, the kidney and pancreas transplantation was not effective in our patients in reversing the clinical and angiographic signs of diabetic retinopathy. Moreover, a worsening of the lesions was observed in some cases; this was probably due to the irreversible microangiopathic lesions due to advanced evolution of diabetes. PMID- 1936706 TI - Effect of pancreas transplantation on diabetic retinopathy: a 20-case report. AB - In order to study the effects of normoglycaemia on diabetic retinopathy, 20 diabetic uraemic patients who underwent a kidney-pancreas transplantation were evaluated before and after surgery (6.9 months and once a year). The control group consisted of 12 uraemic patients who underwent kidney transplantation alone. At each follow-up examination a complete clinical examination and a retinal fluorescein angiography were performed. The eyes with end-stage retinopathy at baseline were excluded from the study. The analysis of the results showed no significant differences in the two groups. The diabetic retinopathy at the moment of the transplantation was already too advanced to benefit from the better glycaemic control. PMID- 1936708 TI - The power of living on the edge. PMID- 1936709 TI - The biopsychosocial model: continued discussion. PMID- 1936707 TI - Diabetic retinopathy and pancreas transplantation: a 3-year follow-up. AB - The effect of simultaneous pancreas and kidney transplantation on diabetic retinopathy was studied in a prospective study with 30 patients (57 eyes) and 15 control subjects (26 eyes), patients who lost the pancreas, but preserved kidney function. There was no significant difference between the groups after a mean observation time of more than 35 months (a range of 12 to 96 months). Both populations had a stable retinopathy during follow-up. This seems to be a consequence of the far advanced retinopathy (mean duration of type 1 diabetes was 22 years) and the high percentage of coagulated eyes (81% and 85%, respectively), but is not related to the organ transplantation. A closer look at the few patients who did not receive laser coagulation (14 patient and 6 control eyes), produced a different result. Four control eyes experienced a significant deterioration of the retinopathy which had been stable before rejection. It is the most important and so far never mentioned aspect of this study, that periods of destabilisation are a definite threat for the retinopathy. Nevertheless, it seems questionable whether we will ever be able to make a definite statement on the pancreas-eye relation, as long as the transplantation must be restricted to carefully selected late-stage diabetic subjects. PMID- 1936710 TI - The context of residency training. PMID- 1936711 TI - Classification in pharyngitis studies. PMID- 1936712 TI - Reliability: why bother? PMID- 1936713 TI - "First of all, do no harm:" the sentence with no indirect object. PMID- 1936714 TI - Parting shot: do our leaders really care about research? PMID- 1936715 TI - Expanding the boundaries of family medicine research. PMID- 1936716 TI - Patient preferences regarding educational pamphlets in the family practice center. AB - Educational pamphlets are widely used in family practice offices despite few studies on patient attitudes toward this educational technique. The purpose of this study was to: 1) determine how frequently patients perceive that pamphlets are used and how often they are desired; 2) determine what is usually done with pamphlets; and 3) determine patient preferences regarding requesting pamphlets, location of unsolicited pamphlets, techniques of getting pamphlets, and style of pamphlets. In this survey of 360 patients, 90% reported wanting a pamphlet at some or all of their office visits. Overall, 67% reported reading or looking through and saving pamphlets received, 30% read or looked through them and then threw them away, and only 2% threw them away without review. Only 11% of males and 26% of females reported ever asking a doctor for pamphlets. Some conclusions are that: 1) more patients desire pamphlets than are receiving them; 2) most patients do save pamphlets; and 3) patients need encouragement and permission to ask for pamphlets. PMID- 1936717 TI - Rapid assessment of literacy levels of adult primary care patients. AB - Health education materials, medical instructions, consent forms, and self-report questionnaires are often given to patients with little regard for their ability to read them. Reading ability is rarely tested in medical settings. The Rapid Estimate of Adult Literacy in Medicine (REALM) was developed as a quick screening tool to assist physicians in identifying patients with limited reading skills and in estimating patient reading levels. This information can be used to tailor materials and instructions to patients' abilities. The REALM and the reading sections of the Peabody Individual Achievement Test-Revised and the Slosson Oral Reading Test were used to test reading ability in 207 adults in six public and private primary care clinics. REALM scores correlated highly with those of the standardized reading tests. The REALM, which takes three to five minutes to administer and score, appears to be a practical instrument to estimate patient literacy in primary care, patient education, and medical research. PMID- 1936718 TI - Relationships between dysfunctional parenting and adolescent symptoms. AB - This study used self-report measures to examine the relationships of parenting practices to seven emotional, behavioral, and somatic symptoms of 66 high school seniors. Dysfunctional parenting, characterized by teens' perceptions of conflict, criticism, negative behavior management, and child dependency, was significantly associated with symptoms experienced by adolescents. Statistical models for each of the seven symptoms indicated that: symptoms of boys were more related to dysfunctional parenting than those of girls; non-parenting variables were only associated with symptoms of girls; and dysfunctional parenting was related more to symptoms of internalizing in boys and externalizing in girls. In addition, conflict with fathers was the parenting variable that was the most predictive of symptoms in both girls and boys, even though both reported having more conflicts with mothers. Dysfunctional parenting by mothers was statistically associated with symptoms but generally contributed less to the models, especially for girls. These findings suggest avenues for early intervention with parents by family physicians when adolescents have certain symptoms. PMID- 1936719 TI - Cognitive factors influencing women to seek care during pregnancy. AB - To assess the relationship of cognitive factors to a pregnant woman's decision to seek prenatal care, a semi-structured interview instrument was administered to 30 women soon after they were seen for care. A content analysis of interview transcripts was performed to identify variables affecting the decision to seek care. Variables were coded numerically, and those correlated with number of weeks gestation at first visit for pregnancy care were entered into a stepwise linear multiple regression model. Three variables accounted for 74% of the variance in the week of gestation at which pregnancy care began. Women who desired the pregnancy, wished confirmation of the pregnancy, and experienced pregnancy related symptoms tended to seek care earlier. Results were discussed in terms of the usefulness of this integration of quantitative and qualitative methods for the study of factors related to seeking pregnancy care and the need to consider cognitive factors when designing programs to improve the delivery of prenatal care. PMID- 1936720 TI - An analysis of reasons for discontinuing participation in a practice-based research network. AB - Now that primary care practice-based research networks are known to be feasible, it is important to learn more about the reasons practices participate and withdraw. The Ambulatory Sentinel Practice Network (ASPN) experience presents a special opportunity to study 32 practices that withdrew from the Network since it began in 1982. One hundred percent of these practices responded to a structured telephone survey. The desire to be part of a group doing research (47%) and response to recruitment by an esteemed colleague (28%) were the most important reasons for joining the Network. Changes within the practice (50%), the additional burdens associated with ASPN (22%), and lack of support among practice colleagues and staff (13%) were the most important reasons for withdrawing. Six suggestions were made that could have helped these practices continue in ASPN. Thirteen percent of practices that withdrew rejoined the Network at a later date. Eight years after initiating investigations, 70% of the practices that were ever part of ASPN remained fully involved. PMID- 1936721 TI - Applying the concept of the reflective practitioner to understanding and teaching family medicine. AB - This article contends that what makes family practice unique as a medical specialty is not so much its content (eg, continuity of care, broad range of patient population) as it is the process of clinical practice (ie, how the specialty is actually practiced in ongoing patient encounters). However, insufficient attention has been paid to critically analyzing and interpreting this process. We present a model derived from other "practice professions," such as architecture, known as reflection-in-action. This model is offered as a way of first apprehending and subsequently teaching the "professional artistry" which constitutes a critical component of family practice. Specific teaching approaches designed to enhance reflective medical practice are delineated. PMID- 1936722 TI - Evaluation of cost-effectiveness research: a survey of recent publications. AB - Because of interest in cost containment, a series of basic guidelines for performing cost-effectiveness research has evolved in the past decade. These guidelines advise that the perspective of the cost study be clarified, that all applicable costs, benefits, and health outcomes be included, and that discounting and sensitivity analyses be performed where appropriate. A survey of 47 recent cost-effectiveness publications selected via MEDLINE and manual searches confirms our hypothesis that many studies do not adhere to these guidelines. Since such short-comings can lead to misleading or ill-founded conclusions, attention must be paid to the principles of cost-effectiveness research to avoid making major, inappropriate health policy decisions. PMID- 1936723 TI - An evaluation of readable preventive health messages. AB - Distributing printed preventive health material has not been shown to change patient behavior. The lack of effect could be due to unreadable or boring materials. This could be corrected by choosing appropriate literature for each patient. A computer program was written to print booklets of relevant preventive health information matched by SMOG or Spache readability scores to a patient's self-reported educational level. The system was evaluated by printing booklets for 81 randomly selected new patients entering a family practice residency clinic setting, using the clinic's health history questionnaire to choose relevant preventive health information. After three months, patients showed no increase in obtaining flexible sigmoidoscopy, diphtheria-tetanus boosters, or cholesterol screens, when compared to 213 control patients. Use of readability matched materials in patient education efforts is logical, but was not sufficient to affect preventive health behavior in this study. PMID- 1936724 TI - Intolerance of ambiguity among family practice residents. AB - The art of clinical medicine involves learning to deal with varying levels of ambiguity and uncertainty. Tolerance of ambiguity was examined by giving Budner's Intolerance of Ambiguity Scale to a sample of 37 family practice residents from a university hospital residency and 22 from a community hospital residency. Residents in both the community and university programs had similar scores. No differences existed between men and women. Compared to studies of medical students, first-year family practice residents were slightly more intolerant of ambiguity. However, intolerance of ambiguity was lower among third-year residents, suggesting that as training advances, residents may become more tolerant of ambiguity. The residency training process may lead to a reduction in intolerance of ambiguity, which produces physicians who can deal with the ambiguity and uncertainty of clinical practice. PMID- 1936725 TI - Prescriptions for saying good-bye: teaching termination to family practice residents. AB - Physicians terminate doctor-patient relationships at various times during their careers. Preparing physicians for this process should be part of residency training in family practice. This report describes the structured role-playing exercises and physician scripts used to teach termination skills. Evaluation of these teaching methods suggests that residents value termination instruction, prefer participative approaches, and report greater sensitivity to the feelings and issues evoked by termination. PMID- 1936726 TI - Obstetrics in family practice: the controversy continues. PMID- 1936727 TI - From idea to publication: the study of chest pain in the development of the Ambulatory Sentinel Practice Network. PMID- 1936728 TI - Our struggle with words and visions. PMID- 1936729 TI - A comparison of psychosocial characteristics of new widowers and married men. AB - Bereavement is a stressful event for men, yet there are few studies that help explain the important psychological and social factors that may interfere with or facilitate the grieving process in men. The purpose of this study is to describe some of these factors in new widowers and to compare them with those in married men. A community sample of 113 widowers bereaved less than 12 months and a family practice clinic sample of 111 married men matched for age were compared on five psychological and social measures (General Health Questionnaire, Beck Depression Inventory, State-Anxiety Inventory, Social Adjustment Scale, and Social Support Questionnaire). The results indicate significantly more distress in the widowers than in the married men. Highly distressed widowers had more problems with work outside the home, housework, and spare time, and they were younger and less satisfied with their social support than less distressed widowers. Widowers younger than 65 years were significantly more depressed and anxious, and had more social adjustment problems than widowers older than 65. These findings may be useful for longitudinal or intervention studies of widowers and may be of value for primary health care providers. PMID- 1936730 TI - Characteristics of non-cobalamin deficient patients who receive regular cyanocobalamin injections. AB - For decades Vitamin B12 injections have been administered to patients with no documented deficiency. A previous study identified a cohort of patients who described vitamin B12-responsive symptoms despite lack of cobalamin deficiency as measured by conventional laboratory tests. These patients have been studied further and, when compared with controls, were found to have had more prescriptions for psychoactive drugs (P less than .001) and to have had more hospitalizations related to symptoms suggestive of neuropsychiatric problems (P less than .01). To confirm these findings and to determine national estimates for vitamin B12 use, an analysis of the 1985 National Ambulatory Medical Care Survey (NAMCS) was conducted. This analysis supports a significantly higher frequency of neuropsychiatric complaints among patients who received vitamin B12 injections (P less than .001). In addition, the NAMCS analysis indicates that of the calculated 2,516,564 vitamin B12 injections given in 1985, only 376,488 were for a diagnosis compatible with a cobalamin deficiency state (a 7:1 observed over expected ratio). According to the national data set analysis, vitamin B12 injections are given most frequently in the rural south by a doctor of osteopathy in solo practice. PMID- 1936731 TI - The relationship between breast-feeding and early childhood morbidity in a general population. AB - This study investigated the relationship between breast-feeding and early childhood morbidity. Data on morbidity had been recorded in the Continuous Morbidity Registration of the Department of Family Medicine of the University of Nijmegen, the Netherlands, since 1967. Information on early childhood feeding was collected retrospectively by questionnaires mailed to the parents of all the children; the response rate was 94%. Exposure and outcome data of 1,347 children were available for analyses. Duration of breast-feeding was categorized as follows: 0 days (no breast-feeding), 1-14 days, 15-30 days, 31-90 days, 91-180 days, and more than 180 days. Two thirds of the children had been breast fed. Generally there was an inverse relationship between breast-feeding and morbidity. This was most prominent in the first year of life but was also present in the first three years. After adjustment for potential confounding variables, duration of breast-feeding was associated with fewer morbidity episodes and lower rates of several specific illnesses during the first three years of life. The findings suggest some modest health benefits of breast-feeding for children in the Netherlands. PMID- 1936732 TI - A national study of required family medicine clinical rotations. AB - The authors collected information from each family medicine department with a required clinical rotation. Timing of such rotations are predominantly during the third year (56%), using a combination of family practice centers and community preceptor sites. Formal didactic instructions are offered for a mean of 28 hours. This instruction is offered in combinations of introductory, weekly, and terminal didactic blocks. Most programs (68%) assign reading from an article file, and 51% develop their own examinations. Clinical evaluations represent the largest portion (61%) of final grades, with 30% coming from examinations and lesser amounts from home visits, student presentations, etc. The implications of these findings are discussed. PMID- 1936733 TI - Why students chose family medicine: state schools graduating the most family physicians. AB - This study identifies factors which influenced a career choice of family practice by students from the class of 1990 in the public medical schools that have graduated the most family physicians in the last decade. One hundred and thirty nine new graduates who entered family practice residencies in 1990 responded to a questionnaire that determined the importance of curricula, teachers, departmental support, practice characteristics, and personal issues in decision making. Practice characteristics of family practice and the clinical curriculum were found to be the most important influences. Differences among subjects on the basis of their levels of interest in family practice prior to medical school were examined. Educational considerations, related to curricula and teachers, were more important to those students with little or no prior interest, whereas practice characteristics and personal issues were more important to students with high levels of prior interest. Implications for educational planning are discussed. PMID- 1936734 TI - Factors involved in successful psychotherapy referral in rural primary care. AB - Many primary care patients are identified as needing psychotherapy. Often family physicians choose to refer these patients for comprehensive treatment, yet psychotherapy referrals are traditionally difficult to transact successfully in comparison with referrals for other biomedical complaints. Previous reports have been published on the beliefs held by family physicians and psychologists regarding factors that affect the success of a referral. This follow-up study reviewed 138 referrals from rural family physicians to psychotherapists. Fifty nine percent of the referrals were considered successful by the family physicians and 73% by the patients. Successful psychotherapy referral, as evaluated by physicians, was related to psychotherapist-initiated post-referral communication with the referring physician. There was no relationship between success of referral outcome and the number of preparatory (or follow-up) visits with the physician, physician's knowledge about the psychotherapy process, patient economic status, or insurance coverage. However, attending more than one therapy session was associated with the number of physician visits prior to referral, distance to the therapist's office, and referral by a physician who included counseling in his or her practice. Findings indicate that when physicians are kept informed about patients' treatment, they are more likely to evaluate the treatments as beneficial. PMID- 1936736 TI - Naming the illness: the power of words. AB - A key part of the doctor-patient encounter is the giving of a name to the patient's illness by the physician. Personal, professional, societal, and bureaucratic factors influence physicians in their choice of a name and the manner in which they present these words to the patient. The effect of the illness name on the individual patient may be determined not only by individual experience and knowledge, but also by social, cultural, and economic factors. Citing examples from medical practice from its origins in ancient Greece to the present day, this paper draws attention to the crucial significance of medical language in doctor-patient communication. A heightened awareness by physicians of communication style is suggested, both in encounters with patients and in the training of medical students and residents. PMID- 1936735 TI - Painters and patients: how art informs medicine. AB - This essay describes three movements in art--impressionism, cubism, and abstract expressionism--and how artists within each movement differed in their portrayal of reality. With this background, the author proposes that inquiry into the motives and methods of artists within each movement may help in our understanding of how a person experiences, interprets, and portrays reality. This, in turn, may translate into a recognition of the multiplicity of perspectives and the uniqueness of each patient's lived experience of his or her illness and that the doctor's vantage point on reality may not mesh with that of the patient. PMID- 1936737 TI - Survey sampling issues in primary care research. AB - Survey research methods are often used to answer questions in primary care medicine. Consequently, investigators must understand and address sampling issues. Probability sampling designs have particular utility for questions that seem most appropriate for survey research. These designs provide each member of the population with a known probability of selection, and if performed properly with an appropriate sample size, they provide a sample with essentially no selection bias. Examples of random and stratified sampling designs are presented. These two probability designs, along with nonprobability sampling techniques (convenience, purposive, quota), are discussed in terms of bias, error, and possible limitations. PMID- 1936738 TI - A comparison of eye problems in primary care and ophthalmology practices. AB - This study compares the most frequent presenting complaints and diagnoses of eye problems in primary care physician and ophthalmologist offices sampled by the 1985 National Ambulatory Medical Care Survey. The data show that primary care patients (seen by family/general physicians, internists, and pediatricians) with eye complaints constitute 2% of all patient visits and are predominantly for minor inflammatory (58%), traumatic conditions and foreign bodies (8.4%), visual disturbances (15.5%), and eyelid problems (3.9%). Conjunctivitis and corneal abrasion accounted for 54.4% of these diagnoses. Patients see ophthalmologists predominantly for vision problems (35.5%), eye exams (24.1%), and inflammatory conditions (24%). Refractive errors, cataracts, and glaucoma constituted 52.7% of ophthalmologist diagnoses. This study provides significant implications for curricular development. Medical schools, primary care residencies, and continuing medical education settings for primary care should emphasize in-depth knowledge of minor ocular inflammatory conditions, eye trauma, visual disturbances, and eyelid problems, as these areas encompass more than 85% of the eye problems seen by primary care physicians. PMID- 1936739 TI - A process evaluation of a required primary care clerkship. AB - A process evaluation was implemented to guide faculty in developing a new required primary care clerkship. During the first eight months of the clerkship, 23 medical students were observed in a time and motion analysis and a study of the verbal content of the precepting interactions as students presented their patients to a preceptor. Students spent an average of 44% of their clinic time in examination rooms with patients, 21% interacting with preceptors and 13% waiting without interaction. The verbal behaviors accounting for 80% of the student preceptor interaction time were case presentations (50%), direct or indirect questioning (16%), and making recommendations for management (13%). PMID- 1936740 TI - [Echocardiographic assessment of segmental kinetic changes of the left ventricle during ischemic attacks induced by slow hyperventilation]. AB - The detection of stress-induced wall motion abnormalities by means of 2D Echo represents a reliable marker of ischemia. Few reports about two-dimensional echocardiography and provocative tests in patients suffering from primary angina are available in the literature. Twenty patients with electrocardiographically documented ischemic transitory attacks at rest underwent hyperventilation test 2 15 days after a spontaneous episode. A new wall motion abnormality and/or a worsening of an asynergy already present at rest occurred in ten patients; eight of them also showed diagnostic ECG changes. Wall motion abnormalities arose significantly earlier (from the end of hyperventilation: 1.7 +/- .84 vs 2.16 +/- 1.15 min, p less than .05). Three patients had angina, which, in all patients started after echocardiographic and ECG changes. All patients experienced paresthesia, and two patients tinnitus due to blood alkalosis. No clinical adverse reaction resulted from the test. Only one patient had ventricular arrhythmias in the recovery phase of the ischemia. IN CONCLUSION: As concerns hyperventilation test, echocardiography has proven useful in identifying myocardial ischemia, comparable to electrocardiography. Moreover, in this study some patients had echocardiographic but not electrocardiographic changes as ischemic manifestations. Events after induction of ischemia with hyperventilation seem to follow the same sequence already observed in spontaneous attacks. PMID- 1936741 TI - [Can the changes in dietary fat intake reduce the risk of onset and development of atherosclerosis and of ischemic cardiopathy in particular?]. AB - In this review we have collected data from epidemiologic studies and clinical trials published from 1968 to 1989 on the relationship between dietary fat and risk of coronary heart disease. Although the reported observational studies of diet and coronary heart disease provide general support for the classic diet heart hypothesis, evidence of specific dietary lipids is weak. A positive association with saturated fat intake was seen in two prospective studies. A positive association with cholesterol intake was found in only two cohort studies, and an inverse relationship with polyunsaturated fat intake in only one. Clear evidence from dietary trials in the prevention of coronary heart disease has not been found. The analysis of trends in coronary heart disease and stroke mortality of developed countries has shown a discrepancy between fat intakes, cholesterol levels and mortality. The reduction in intake of certain foods "at high risk" such as meat, eggs, milk and cheese, as a preventive intervention, is based on weak scientific evidence. A strategy program has to emphasize the maintenance of ideal body weight by caloric control, an adequate level of physical activity, and the control of other risk factors such as hypertension, hypercholesterolemia, and diabetes. PMID- 1936742 TI - [Thallium and echo- dipyridamole in the early selection of patients at risk after acute myocardial infarction. Which test? What dose?]. AB - The optimal iv dose of Dipyridamole (Dip) in echocardiography (echo) or Thallium scintigraphy (Tl) remains undetermined. To select the high-risk patients (pts) subset, we performed echo and Tl with standard dose (SD) and high dose (HD) Dip infusion (0.56 mg/Kg/4'-0.84 mg/Kg/10' respectively) in 40 pts 9 +/- 3 days after admission for acute myocardial infarction (AMI). Of these, 38 pts had coronary artery disease at angiography and 2 had no significant lesions. Worsening in regional wall motion on echo and reversible perfusion defects on Tl were considered abnormal patterns. SD had no side effects; only in one pt was ischemic ventricular dysfunction detected on echo, whereas Tl redistribution was found in 24 pts (12 had multivessel disease and 12 had one coronary stenosis greater than or equal to 70%). HD caused adverse reaction in 24 pts, did not enhance SD-Tl sensitivity, but induced abnormal echo in 18/24 pts with transient defects on SD Tl. Eleven of the 16 Tl negative pts had occlusive disease, 3 had one vessel disease and 2 showed no evidence of coronary artery disease. IN CONCLUSION: SD is safe but often provokes a submaximal coronary vasodilation. Failure to detect ischemia on echo may be explained by this. SD-Tl is, however, able to identify high-risk pts who may benefit from early myocardial revascularization. HD does not enhance SD-Tl sensitivity, but it is necessary to induce echo abnormalities which are all too often undetectable at SD. PMID- 1936743 TI - [Influence of age on the short- and medium-term prognosis in patients with acute myocardial infarct]. AB - Elderly patients with acute myocardial infarction (AMI) have a higher subsequent mortality than younger ones, yet the reasons for this adverse prognosis are poorly understood. We compared the clinical course and the prognosis of 163 patients aged 40 to 69 years with 112 patients older than 70 years. During hospitalization period 15.9% of younger and 37.5% of older patients died; at 1 year follow-up the cardiac mortality rate was 8.7% in younger and 12.9% in older patients. In elderly patients a greater prevalence of female gender, diabetes mellitus, anterior myocardial infarction, atrial fibrillation and a greater incidence of heart failure and shock were observed. Multivariate stepwise analysis identified shock and heart rate greater than or equal to 90 bpm at the time of admission as the most important prognostic variables for in-hospital mortality in both groups; heart failure (Killip class II and III) was significant in younger patients, while non Q wave myocardial infarction correlated with a better prognosis in elderly. In elderly patients who survived AMI, predischarge Holter monitoring showed higher frequency and complexity of ventricular arrhythmias, and radionuclide angiography lower left ventricular ejection fraction (E.F.) values. In these patients no difference was found in E.F. values despite myocardial infarction sites. At 1 year follow-up E.F. less than 40% and ventricular arrhythmias (3-4 Moss grading system) were significantly related to prognosis in younger patients, while E.F. less than 40% and clinical signs of heart failure in elderly. Therefore, low E.F. and heart failure account for a worse prognosis in elderly patients, while ventricular arrhythmias in younger ones. The results of this study support aggressive management even in elderly patients following AMI to preserve left ventricular function. In elderly patients a large use of antiarrhythmic drugs is not recommended because of low prognostic value of ventricular arrhythmias. PMID- 1936744 TI - [Usefulness of pulsed doppler echocardiography in the diagnosis and medical therapy of patent ductus arteriosus in the newborn with respiratory distress]. AB - In preterm infants patent ductus arteriosus (PDA) may worsen the clinical course of Respiratory Distress Syndrome (RDS). Indomethacin is usually effective in producing duct closure in the first days of life, but clinical diagnosis is often difficult to perform in these patients. In recent years Pulsed Doppler Cross Sectional Echocardiography (PD-CSE) has made it possible to identify the duct and to assess noninvasively the characteristics of blood flow within it. The aim of this study was to verify the utility of PD-CSE in the early diagnosis of PDA and to provide the basis for a more effective drug therapy. Among 51 patients with RDS, a significant PDA was evidenced in 20 with PD-CSE and in only 8/20 with physical and E-TM examination (p less than 0.01). Indomethacin administration produced duct closure in 19/20 patients (95%). In this study PD-CSE has been more sensitive than the other noninvasive procedures in the diagnosis of PDA; moreover, the success with drug therapy demonstrates the utility of this procedure in providing the basis of a more effective treatment of the duct. PMID- 1936745 TI - [Trend of mortality in ischemic cardiopathy and other cardiovascular diseases in Italy from 1970 to 1986. Their subdivision into sex and geographic area]. PMID- 1936746 TI - [Characterization of intracardial blood flow with Doppler color in a case of right ventricular myxoma]. AB - The authors describe the color flow pattern in a patient with right ventricle myxoma and outflow obstruction. A systolic eccentric mosaic color jet, flowing in a thin space between the tumor and the right ventricle outlet wall, was observed. The color Doppler imaging easily detected flow abnormalities, greatly simplified the correct alignment of continuous wave Doppler beam in the estimation of the pressure gradient and allowed a good evaluation of tumor hemodynamic effects. PMID- 1936747 TI - [Myocardial involvement in granulomatous vasculitis (Churg-Strauss disease)]. AB - We report the case of a 44-year-old woman affected by Churg-Strauss syndrome (systemic vasculitis with eosinophilia, bronchial asthma and pulmonary infiltrations). Congestive heart failure developed, caused by severe myocardial and pulmonary involvement. Conventional treatment and steroids induced remission of symptoms. PMID- 1936748 TI - [Trisomy 18 associated with atrioventricular canal]. AB - We describe the clinical and necropsy findings of a newborn with trisomy 18 and atrioventricular canal. The patient also showed an aortic coarctation, a dysplasia of the common atrioventricular valve and multiple extracardiac anomalies. The atrioventricular canal, so frequent in patients with trisomy 21, is unusual in trisomy 18. The present case is the 6th of the medical literature. PMID- 1936749 TI - [Stratification of arrhythmic risk]. PMID- 1936750 TI - [Cardiology and bioethics]. PMID- 1936751 TI - [Prognostic stratification of non complicated acute myocardial infarct. Usefulness of the dipyridamole test with ecg-echo-thallium 201]. AB - 84 patients (pts) with recent first uncomplicated myocardial infarction underwent during the early post-infarction period, dipyridamole (D) test (EKG-ECHO THALLIUM) and coronary arteriography in order to verify its feasibility, safety and usefulness in the detection of residual jeopardized but viable myocardium and in the diagnosis of multivessel disease. 69 pts performed a pre-discharge exercise test. During the execution of D test no major side effect occurred. The D-Echo was positive for residual ischemia in 41 pts (48.8%), the D-Thallium in 49 pts (58.3%) and the exercise test in 30 pts (43.5%). Both the imaging techniques allow the recognition of viable myocardium within the infarct zone (homozonal positivity) or outside the infarct zone (heterozonal positivity). The sensibility and specificity for multivessel disease are, respectively: with D-echo 50% and 100%; with D-thallium 60% and 100%; with exercise test 48% and 63%. D test has better diagnostic accuracy than exercise test in detecting multivessel disease; in particular we emphasized the excellent specificity of D-echo and D-thallium test. Poliparametric approach with D-test and exercise test gives a better stratification of the ischemic post-infarction risk. PMID- 1936752 TI - [The echo-dobutamine test for the diagnosis of myocardial ischemia. Study on 20 patients with normal kinetics at rest]. AB - We have assessed the value of dobutamine stress echocardiography for the diagnosis of myocardial ischemia in 20 consecutive patients referred for chest pain, without a previous myocardial infarction and with a normal left ventricular wall motion at rest. The test was considered positive when wall motion abnormalities appeared during dobutamine infusion (from 5 to a maximum of 40 micrograms/Kg/min). The results were compared to the % diameter stenosis (%DS) quantitatively measured on coronary arteriography. "Significant" coronary artery disease was defined as greater than or equal to 50% DS. No significant side effects occurred in any patients during the test. Transient wall motion abnormalities were detected in 8 of the 12 patients with significant coronary artery disease (sensitivity = 66%) and in 1 of the 8 patients without significant coronary artery disease (specificity = 88%). All the patients with false-negative dobutamine stress echocardiography had distal stenosis or stenosis in a collateral vessel; moreover, all the patients with true-positive dobutamine stress echocardiography had proximal (7 patients) or middle (1 patient) stenosis. The results of this study show that dobutamine stress echocardiography is a safe and feasible test for the noninvasive diagnosis of myocardial ischemia. PMID- 1936753 TI - [Effects of acute and chronic administration of verapamil on the anatomy and function of the left ventricle in essential hypertensive patients ]. AB - The aim of this study was to analyze the acute and chronic effects of oral verapamil on diastolic function indices, derived from Doppler echocardiography and left ventricular (LV) dimensions and mass, assessed by M-mode echocardiography, in hypertensive patients (pts). Twelve essential hypertensive pts without LV hypertrophy were studied in basal conditions and 1) after a single oral administration of verapamil 160 mg and placebo, in double blind protocol and 2) over chronic treatment (six months) of verapamil 240 mg/day. At baseline the ratio between early and atrial-induced transmitral velocities (E/A ratio) was lower in pts than in 12 age-matched normal subjects (1.0 +/- 0.3 vs 1.5 +/- 0.3, p less than 0.01). Acute verapamil administration significantly decreased arterial blood pressure (162 +/- 26/101 +/- 15 to 142 +/- 12/88 +/- 7 mmHg, p less than 0.01) after two hours and increased the E/A ratio to 1.26 +/- 0.3 (p less than 0.05) after three hours. No change in ventricular dimensions or heart rate was observed. After chronic therapy we found a further increase in the E/A ratio (1.49 +/- 0.3, p less than 0.01) in 10 responder pts. The LV mass index, which was higher than in normal subjects before the treatment (118 +/- 16 vs 91 +/- 11 g/m2, p less than 0.01), was significantly reduced (100 +/- 17 g/m2, p less than 0.05 vs basal, ns vs normal subjects). Our results demonstrate that acute administration of verapamil only partially improves the abnormal indices of diastolic function in hypertensive pts, whereas chronic treatment, by reducing left ventricular mass indices and blood pressure to normal values, can completely normalize the indices of LV diastolic filling. PMID- 1936754 TI - [Dynamic electrocardiogram in chronic atrial fibrillation treated with digitalis]. AB - To assess heart rate variability in chronic atrial fibrillation, 60 patients (20 men, 40 women: mean age 63 +/- 8 years: NYHA 2.0 +/- 0.5) with various cardiac conditions were investigated with 24-hour Holter monitoring during daily life. Twenty-five healthy subjects (5 men, 20 women: mean age 55 +/- 9) were considered as the control group. All patients had "controlled" heart rate (50-90 bpm) on basal ECG, normal hematological and thyroid hormone values, and took digoxin alone (mean dosage 0.22 +/- 0.05 mg). Mean digoxin plasma levels were 0.88 +/- 0.48 ng/ml. Maximum, minimum and average heart rate were quite good during the night but too high during the daytime and far higher than those observed in healthy subjects. In fact, up to 82% of patients (at 9 a.m.) had a maximum heart rate higher than 115 bpm. Pauses between 2.0 and 3.0 sec occurred in 40 out of 60 patients (66%). No patients had pauses longer than 4.0 sec. In our experience, patients in chronic atrial fibrillation "controlled" with digoxin alone showed a daytime heart rate which was often too high. We suggest 24-hour Holter monitoring to detect subgroups that may be treated successfully with digoxin associated with calcium-antagonists or beta-blockers. PMID- 1936755 TI - [Left ventricular systolic function in patients surgically treated for atrioventricular septal defect: echocardiographic assessment]. AB - In order to assess the left ventricular systolic function we studied by echo 14 pts (8M, 6F) with complete atrioventricular septal defect (AVSD) who had undergone surgical repair. Mean age was 20.30 +/- 24.63 months, with a follow-up of 52.85 +/- 19.11%; in 6 pts Down syndrome was associated. Particularly, we tried to determine whether the following factors might affect the post-operative left ventricular systolic function: a) Down syndrome; b) residual mild mitral regurgitation; c) age of the surgical repair; d) length of the follow-up. As load independent indexes of contractility, the left ventricular end systolic stress (LVESS)-circumferential fibre shortening velocity normalized for heart rate (VCFc) relationship and the LVESS/end systolic volume index (ESVI) ratio were chosen. All pts showed normal (mean +/- 2 standard deviations) or slightly higher values of LVESS/VCFc relationship; significantly, the only two pts with lower values had later undergone surgical repair. LVESS/ESVI ratio confirmed an inverse relationship between systolic function and age of the surgical correction (r = 0.75); no other factors (Down syndrome, residual mild mitral regurgitation, length of the follow-up) showed a significant correlation with the post-operative left ventricular systolic function. In conclusion, in our limited population, the age of the surgical repair appears to be the main factor affecting the post surgical left ventricular systolic function in pts with complete AVSD. PMID- 1936757 TI - [Antiplatelet effects of nitrate derivatives]. AB - Nitrates are among the most widely prescribed drugs in cardiovascular disease. They are able to prevent and to interrupt episodes of myocardial ischaemia, alleviate anginal symptoms, and exert favourable effects in acute myocardial infarction and in congestive heart failure. Most of these effects can be explained by their ability to relax smooth muscle cells: peripheral vasodilation, in veins and in arteries, reduces cardiac workload, thereby decreasing oxygen consumption; furthermore, nitrates dilate coronary arteries directly, thereby increasing myocardial oxygen supply. However, nitrates also exert effects on blood platelets. These occur by the same mechanisms operating on blood vessels, a stimulation of soluble guanylate cyclase and a consequent increase in cytosolic levels of cyclic GMP. When added to platelet suspensions nitrates inhibit platelet aggregation by almost all known stimuli. Such effects in vitro generally require high concentrations of drugs; evidence has been obtained, however, that nitrates may inhibit platelet function also in vivo. Such evidence derives from ex vivo studies with platelet aggregometry, from experiments showing the synergism of nitrates and prostacyclin and the requirement for nitrate action of sulphydryl group donors such as N-acetyl-cysteine, and from studies on bleeding time. Antiplatelet effects of nitrates may be an explanation for the protection from death and reinfarction, inferred on the basis of meta-analysis of several studies in acute myocardial infarction. PMID- 1936756 TI - [Significance of the degree of oxidative hepatic metabolism in conditioning the pharmacokinetics and the pharmacodynamics of propafenone]. AB - The aim of this study was to evaluate plasma concentrations of propafenone (P) and 5-hydroxy-propafenone (5-OH-P) at steady state in 36 patients with ventricular premature beats, Lown class greater than or equal to 2, submitted to antiarrhythmic treatment with propafenone either in acute administration (AA) (300-450 mg) or in chronic administration (CA) (150-300 mg t.i.d. for 14-21 days followed by a wash out), and to define the relationship existing between metabolic oxidative capacity and P and 5-OH-P pharmacokinetics and pharmacodynamics. Antiarrhythmic treatment resulted efficacious in 31/36 cases (86%) during AA and in 28/36 cases (78%) during CA. At steady state a wide interindividual variability was observed in plasma concentrations of P (mean = 835 +/- 619 ng/ml, coefficient of variation = 74%), in plasma concentrations of 5 OH-P (mean = 142 +/- 93 ng/ml, coefficient of variation = 65%) and of their ratio (mean = 6.51 +/- 8.53, coefficient of variation = 131%), without significant differences between responders and nonresponders. In a subgroup of 14 subjects, characterized as extensive oxidizers of dbrisoquine, a significant correlation (r = 0.97, p less than 0.001) was observed between the ratio of P and 5-OH-P plasma concentrations at steady state and oxidative metabolic capacity (expressed as debrisoquine/4-hydroxy-debrisoquine ratio). Oxidative metabolic capacity was also correlated with P half life (r = 0.82, p less than 0.002 in AA and in CA) and with the ratio of P and 5-OH-P area under curve (r = 0.91, p less than 0.001 in AA and r = 0.90) changes at the electrocardiogram (mean values = + 20% for QRS, +26% for PR). In conclusion, oxidative metabolic pathway is a crucial point in propafenone metabolization; indeed the extent of metabolic oxidative capacity, evaluable by analysis of debrisoquine oxidation, is responsible for a wide interindividual variability of P and 5-OH-P plasma concentrations, present even in a population of debrisoquine extensive oxidizers and, moreover, influences the extent of electrocardiographic changes of PR and QRS intervals, which are related to 5-OH-P plasma levels, but not to P plasma levels. PMID- 1936758 TI - [The heart in pheochromocytoma: hemodynamic, electrocardiographic, and echocardiographic aspects]. PMID- 1936759 TI - Concentric left ventricular wall thickening in a patient with primary hypothyroidism. Response to gradual thyroxine replacement. AB - Asymmetric septal thickening has been described in patients with overt myxedema, but descriptions of concentric left ventricular wall thickening in such patients are rare. Echocardiographic detection of thickened left ventricular and interventricular walls, without pericardial effusion or any other sign of cardiac involvement, in a patient with overt myxedema and primary hypothyroidism, is reported. Furthermore, this is the first case in which the timing and the extent of the response of such abnormalities to L-thyroxine replacement therapy have been serially evaluated. PMID- 1936760 TI - [Hemopericardium caused by cardiac perforation during anticoagulation therapy. Description of 2 cases]. AB - We describe two cases of cardiac tamponade following a right ventricular wall perforation, due to temporary stimulating catheter, during acute myocardial infarction. The pericardial effusion, which occurred after the catheter remotion, could have been favoured by the anticoagulant treatment. PMID- 1936761 TI - [Coronary risk factors: facts and open questions]. PMID- 1936762 TI - [Approaches to the prophylaxis of infective endocarditis in basic medicine: proposal of a survey procedure]. PMID- 1936763 TI - [Ten years of late ventricular potentials]. PMID- 1936765 TI - Intramural hematoma of the esophagus caused by minor head injury 6 hours previously. AB - The diagnosis of extensive intramural hematoma of the esophagus due to a bicycle trauma was considerably delayed because symptoms did not develop until 6 h after the accident. This report underscores the importance of a barium meal and computed tomographic (CT) scan in cases of unexplained chest pain, even after minor trauma. PMID- 1936764 TI - Radiographic evaluation of achalasia immediately after pneumatic dilatation with the Rigiflex dilator. AB - Radiographic evaluation of the lower esophagus was done immediately after pneumatic dilatation using the Rigiflex dilator in 34 patients (24 men, 10 women; mean age, 55 years) with achalasia. The dilator was positioned across the esophagogastic junction using fluoroscopy and the balloon was inflated for 1 min. The esophagus was intubated and injected sequentially with water-soluble and barium contrast materials. Radiographic analysis included changes in the appearance of the caliber and contour of the esophagogastric junction, rate of esophageal emptying, and presence of complications. In 23 patients with predilatation esophagrams, the mean esophagogastric junction caliber increased from 4.7-7.6 mm following dilatation. The postdilatation esophagrams in 33 patients showed a smooth contour in 22 (67%) and immediate esophageal emptying in 26 (79%). Esophageal perforation occurred in one (3%) patient and intramural hematoma in one (3%). Clinical follow-up (mean, 7 months) was available in 29 patients and 23 (79%) had symptomatic improvement. Five of the six patients who did not improve clinically all had previous Heller myotomy, pneumatic dilatation, or both. PMID- 1936766 TI - Extrusion of PEG tube from the stomach with fistula formation: an unusual complication of percutaneous endoscopic gastrostomy. AB - Percutaneous endoscopic gastrostomy (PEG) has become an accepted technique for providing long-term enteral feeding. We report two cases of extrusion of the PEG tube into a short fistulous tract that communicates with the stomach. Although this unusual complication led to difficulty with tube feedings, both patients were asymptomatic, and, in one case, it was possible to reposition another catheter in the stomach via the fistula. PMID- 1936767 TI - Evaluation of tumor growth rate in patients with early gastric carcinoma of the elevated type. AB - The growth rates of elevated-type early gastric carcinoma in 12 patients were determined chronologically using serial radiographs. Eight progressed from an early to an advanced stage during periods of observation ranging from 4-82 months (mean 31.7 months), while four patients were still in an early stage at final examination, despite an increase in tumor size. The tumor volume doubling months) but varied considerably among patients. Aggressive endoscopy should be performed for all elevated lesions of the stomach because they can harbor malignancy; some can grow rapidly as reported here. PMID- 1936769 TI - MRI diagnosis of delayed presentation of traumatic diaphragmatic hernia. AB - Traumatic rupture of the diaphragm may go unrecognized in patients with multiple injuries to the abdomen and chest. The majority of undiagnosed diaphragmatic ruptures will eventually become symptomatic and are associated with a high mortality rate if not treated immediately. Multiplanar imaging with magnetic resonance (MR) provided a definitive diagnosis of delayed presentation of traumatic diaphragmatic hernia. PMID- 1936768 TI - Use of water or air as oral contrast media for computed tomographic study of the gastric wall: comparison of the two techniques. AB - Thirty-four patients with a high suspicion of gastric lesion at endoscopy were studied by two computed tomographic (CT) techniques: one using a gas-producing agent and the other using water as an oral contrast media. Intravenous contrast medium was also given in all patients who underwent the water technique. Final histologic proof was obtained either by endoscopy or at surgery. Both CT techniques detected the wall abnormality in 32 of the 34 patients, and both techniques missed the same lesion in two patients. The water technique showed more gastric wall details and the lesion's limits could be defined more accurately. The acceptance and tolerance of the gas-producing agent was better in severely ill patients than tap water. PMID- 1936770 TI - Diagnostic difficulties with duodenal malignancies revisited: a new strategy. AB - Early diagnosis of a duodenal tumor is essential for effective therapy. Five cases of duodenal tumors are presented. The value of various diagnostic imaging methods in the assessment of tumors is also discussed. Modified duodenography is proposed as a method that should improve the diagnostic accuracy. PMID- 1936771 TI - Length of residual small bowel after partial resection: correlation between radiographic and surgical measurements. AB - The capacity for absorption after a small bowel resection depends upon the remaining length of intestine. This is important in planning nutritional therapy and affects surgical policy should further resection appear necessary. In 18 patients, the remaining small bowel length from the duodenojejunal flexure had been measured at operation and found to be less than 200 cm; this was compared with a measurement obtained by one observer using an opisometer on a subsequent barium follow-through (BaFT) examination. A significant correlation (p less than 0.001) of 0.72 was found. Radiographic measurement was easiest when the bowel was short (less than 150 cm) and all seen on one film with no overlapping loops. A residual small intestinal length of less than 200 cm measured from a BaFT radiograph is sufficiently accurate to formulate management decisions. PMID- 1936772 TI - Pancreatic cavernous hemangioma: CT, MRI, US, and angiography characteristics. AB - A large pancreatic cavernous hemangioma was found in a 30-year-old man with abdominal distention. Plain and contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US), and angiography were performed prior to operation. Contrast-enhanced CT and angiography showed a large poorly enhanced hypovascular tumor at the head of the pancreas. But MRI and US disclosed findings compatible with a cavernous hemangioma. PMID- 1936773 TI - Mesenteric and omental cysts: an ultrasonographic and clinical study of 15 patients. AB - The clinical and ultrasonographic (US) features of 15 cases of mesenteric or omental cyst are herein described. This series included seven male and eight female patients, whose age ranged from 2-89 years. Correct clinical diagnosis was made in two children only, but preoperative US examination accurately demonstrated the lesion in 11 of 13 patients (85%). These cystic lesions usually had a thin wall, internal septations, and fluid content with sedimentation. Enteric duplication cysts had a relatively thick wall merging with the muscle layer of bowel loop, and multiloculation was noted mainly with cystic lymphangiomas or pseudocysts. The diagnostic and surgical management of these lesions are briefly reviewed and their US appearance is illustrated. PMID- 1936774 TI - Accuracy of ultrasound in counting and measuring gallstones. AB - A prospective study of accuracy of ultrasound in measuring and counting gallstones was undertaken in 30 patients undergoing cholecystectomy. Stones were correctly counted (up to five) in 27 of 30 patients. Ninety-three of 106 stones (88%) examined were measured accurately (with a 2 mm error margin). The size of the smaller stones tended to be overestimated, whereas the size of the larger stones tended to be underestimated. When nonoperative treatment of gallstones is considered, ultrasound can be used as the first examination to identify patients who will not be eligible for one or another protocol on the basis of size or number of stones. PMID- 1936775 TI - Agenesis of the right lobe of the liver: case report. AB - Agenesis of the right liver lobe is extremely rare, and only 30 cases of agenesis or hypogenesis of the right hepatic lobe have been reported in the literature. Another case of agenesis of the right lobe of liver is presented herein. Diagnosis was established by computed tomography (CT), liver scintigraphy, and angiography. The radiological findings and differential diagnosis are reviewed. PMID- 1936776 TI - Absence of the left lobe of the liver: US and CT appearance. AB - We report five cases of absence of the left liver lobe diagnosed by ultrasonography (US) and/or computed tomography (CT). There were four men and one woman, with an average age of 62.8 years. The right lobe was normal in four patients and enlarged in one. A tongue-like hypertrophy of the caudate lobe was present in two patients. The gallbladder was located at the left portion of the liver. Elevation of the antrum of the stomach was also seen. PMID- 1936778 TI - Dilated periportal lymphatics mimicking an anastomotic bile leak after liver transplantation. AB - Transhepatic cholangiography is commonly performed during postoperative evaluation of liver transplant patients. The authors describe a potential pitfall in the interpretation of these studies and illustrate that dilated interrupted lymphatics of the donor liver can mimic a periductal leak of contrast material. PMID- 1936777 TI - Anomalous right lobe of the liver: CT appearance. AB - We report five cases of anomalous right lobe of the liver diagnosed by computed tomography (CT). There were three men and two women, with an average age of 67 years. The right lobe was deformed and decreased in size in all patients. Hypertrophy of the left lobe was present in all patients. PMID- 1936779 TI - Hepatosplenic AIDS-related Kaposi's sarcoma. AB - Abdominal ultrasonography (US) and computed tomography (CT) were performed in one patient with acquired immunodeficiency syndrome (AIDS) and biopsy-proven hepatosplenic Kaposi's sarcoma. Small hyperechoic nodules were seen in the liver and spleen at US. CT revealed hepatosplenomegaly and low-attenuation focal lesions in the liver. These findings, although nonspecific, are suggestive of hepatosplenic involvement in Kaposi's sarcoma. PMID- 1936780 TI - Diagnostic accuracy of the double-contrast enema for colonic polyps in patients with or without diverticular disease. AB - The accuracy of the double-contrast enema for the diagnosis of polypoid lesions in the presence or absence of diverticula was evaluated by retrospectively reviewing the medical records of 202 patients subjected to examination and endoscopy. Analysis of the data on 215 polypoid lesions showed that (a) the diagnostic accuracy of the examination is not affected significantly by the presence of diverticula; (b) the sensitivity of the examination is highly dependent on the size of the polyps (smaller or larger than 0.5 cm) but not on the form (sessile or pedunculated); and (c) the positive predictive value is higher in patients without diverticula. The double-contrast enema was confirmed to be a valid method for the diagnosis of polypoid lesions. PMID- 1936781 TI - Angioimmunoblastic lymphadenopathy of the colon with malignant transformation. AB - Angioimmunoblastic lymphadenopathy (AILD) is a rare disorder characterized by lymphadenopathy, constitutional symptoms, skin rashes, and a variety of hematologic disorders. Its occurrence in the colon is rare. Late in the disease, immunosuppression occurs, and there is an increased risk of malignant transformation. We present a case of AILD of the colon with eventual transformation into malignant lymphoma. PMID- 1936782 TI - Gastrointestinal carcinomas in renal transplant recipients. AB - The development of malignancies in renal transplant recipients is well documented. Typically, these are cutaneous tumors or lymphomas. During the past 5 years, we have encountered six patients with documented carcinomas of the gastrointestinal tract, which developed after these patients received renal transplants. These carcinomas developed at an average of 10 years (range 2-16 years) after renal transplantation. There were three carcinomas of the colon, and one each of the esophagus, stomach, and anal canal. In many instances, the patients had examinations prior to transplantation which were normal. Several surveys of transplant recipients indicate there is an increased incidence of gastrointestinal tract malignancies after transplantation. These studies also recommend that screening of the gastrointestinal tract in long-term transplant recipients be performed. Since these patients are often imaged in the radiology department, radiologists must be aware of this possible complication. PMID- 1936783 TI - Fatal pancreatitis secondary to iatrogenic duodenal hematoma: a case report and review of the literature. PMID- 1936784 TI - A critical analysis, with appropriate controls, of gastric acid and pepsin secretion in clinical esophagitis. AB - Because esophagitis is a presumed "acid-peptic" disease, fasting gastric contents (volume and acid and pepsin concentrations) and basal and pentagastrin-stimulated acid and pepsin outputs were studied in 155 patients with endoscopically defined (and graded 1-4) esophagitis and 508 control patients without esophagitis. Basal pepsin and maximal acid and pepsin outputs were lower in the patients with esophagitis than in those without esophagitis. In further analysis, the patients were subdivided into three categories, duodenal ulcer, nonulcer with no disease other than esophagitis, and postgastric surgery, because these categories affect gastric secretion independently of esophageal disease and in the rank order given. Each category was subdivided by sex, because men secreted more than women. Within each category there was no systematic difference in fasting, basal, or maximal gastric acid or pepsin secretion between patients with and patients without esophagitis. Severity of esophagitis was not related to any secretion parameters. Hiatal hernia was present in 50% of patients with esophagitis vs. 15% of controls without the condition (P less than 0.01); however, this did not independently influence the gastric secretion findings. Lower esophageal sphincter pressure was also measured in 62 of the patients, 31 with and 31 without esophagitis. Below 10 mm Hg (incompetent sphincter), 9 of 10 patients had esophagitis but accounted for only less than 30% of the patients with esophagitis, whereas none of 11 patients with basal acid output of less than 0.1 mEq/h and lower esophageal sphincter pressure of greater than 10 mm Hg had esophagitis. Because neither the composition of gastric juice nor basal or stimulated gastric acid or pepsin output could be correlated to the presence or severity of esophagitis, factors other than amount or composition of gastric juice per se must be responsible for susceptibility to esophagitis. PMID- 1936785 TI - Primary B-cell gastric lymphoma: a clinicopathological study of 145 patients. AB - Resection specimens from 145 patients with primary B-cell gastric lymphoma at stage IE (n = 88) and at stage IIE (n = 57) were investigated. Histologically, low-grade malignant B-cell lymphomas arising from the mucosa-associated lymphoid tissue, including immunocytoma (n = 71), could be distinguished from high-grade malignant B-cell lymphomas with (n = 25) and without (n = 49) evidence of a low grade component. The very rare low-grade B-cell lymphomas of centroblastic centrocytic, centrocytic, and plasmacytic type were not considered. All patients had undergone primary gastric resection, and 65 received additional chemotherapy (n = 33), radiotherapy (n = 22), or both (n = 10). Actuarial overall survival rates calculated by the Kaplan-Meier life-table method were 76% after 5 years and 58% after 10 years. According to the Mantel test and a multivariate analysis using the Cox regression method, patients at stage IE had a significantly better survival probability than those at stage IIE (P less than 0.0001); 5-year survival rates were 87% and 61%, respectively. The survival probability for low grade malignant lymphomas was significantly better than for tumors with secondary high-grade transformation (P less than 0.05) or for primary high-grade lymphomas (P less than 0.0001), whereas the two high-grade groups were not significantly different. Five-year survival rates were 91% for low-grade, 73% for secondary high-grade, and 56% for primary high-grade malignant lymphomas. Retrospectively, no significantly different survival rates were found between patients who had undergone gastric resection alone and patients who had received additional treatment. However, survival analyses showed that classification and grading according to the histopathological concept of mucosa-associated lymphoid tissue derived gastric lymphomas into low-grade B-cell lymphomas of mucosa-associated lymphoid tissue type and high-grade B-cell lymphomas with or without evidence of a low-grade component has great prognostic relevance. PMID- 1936786 TI - Value of transrectal ultrasonography in Crohn's disease. AB - Anorectal lesions are common and can develop silently in patients with Crohn's disease. Transrectal ultrasound examinations were performed to study 40 healthy individuals and 40 patients with Crohn's disease. A rigid linear endorectal probe was used to examine the rectal wall, the perirectal tissues, and the anal sphincter. In healthy individuals, the rectal wall showed five layers with a total diameter of maximum 4 mm. The anal sphincter was clearly visualized as an echo-poor and sharply delineated structure. No pathological lesions were detected perirectally. In Crohn's disease, an enlargement of the rectal wall was seen in 16 patients and heterogeneity of the anal sphincter in 19 patients. This technique detected lesions missed with the routine proctological examinations: four pararectal abscesses, two pararectal fistulas, two para-anal abscesses, and one para-anal fistula. In all examined subjects, the anal sphincter increased in breadth during squeezing and in length during straining. It is concluded that transrectal ultrasonography sharply delineates the rectal wall and the anal sphincter at rest and under dynamic conditions and detects unknown abscesses and fistulas in the pararectal and para-anal tissues in patients with Crohn's disease. PMID- 1936787 TI - gamma-Aminobutyric acid localization and function as modulator of cholinergic neurotransmission in rat antral mucosal/submucosal fragments. AB - gamma-Aminobutyric acid, a neurotransmitter in the central nervous system, has been shown to be present in and synthesized and secreted by rodent and feline myenteric plexus neurons. The aims of the present studies were to measure gamma aminobutyric acid concentrations and synthesis and to establish cellular localization and uptake of gamma-aminobutyric acid by immunocytochemistry and autoradiography, respectively, within mucosal and submucosal tissues of the rat antrum. Direct demonstration of [3H]gamma-aminobutyric acid release and the effects of exogenous gamma-aminobutyric acid and muscimol, a GABA alpha agonist, on [3H]acetylcholine release from antral mucosal/submucosal fragments were examined in perifusion experiments. gamma-Aminobutyric acid content and synthesis, as reflected by glutamic acid decarboxylase activity, were present within antral mucosa at levels two to three times that of the body and muscular layers of both the gastric body and antrum. gamma-Aminobutyric acid was identified immunocytochemically, principally in mucosal epithelial cells of the antrum. Exogenous gamma-aminobutyric acid and muscimol were capable of stimulating acetylcholine release through a GABA alpha receptor-mediated mechanism that was abolished by tetrodotoxin. These results indicate that gamma aminobutyric acid is present in and taken up by epithelial cells of the gastric antrum and that gamma-aminobutyric acid is capable of being synthesized by antral mucosal/submucosal tissues. Furthermore, these studies suggest that a peripheral gamma-aminobutyric acid mechanism that may modulate cholinergic neurotransmission and endocrine cell function exists within the antrum. PMID- 1936788 TI - Histological maturity of healed duodenal ulcers and ulcer recurrence after treatment with colloidal bismuth subcitrate or cimetidine. AB - The relationship between histological maturity of healed duodenal ulcers and ulcer recurrence after 6 weeks of treatment with colloidal bismuth subcitrate or cimetidine was investigated. There was no significant difference in healing rates between colloidal bismuth subcitrate- and cimetidine-treated patients (85.7% and 71.8%, respectively; P greater than 0.05). Histologically, the regenerating mucosa of healed ulcers was divided into three categories--good, fair, and poor- according to pattern. Sixty percent of healed colloidal bismuth subcitrate treated and 30.9% of healed cimetidine-treated ulcers had a good pattern; the difference was statistically significant (P = 0.027). The difference in recurrence rates between healed colloidal bismuth subcitrate-treated and healed cimetidine-treated patients was statistically significant at 3 months (3.45% and 20%, respectively; P = 0.044). All recurrent ulcers in both groups had fair or poor patterns of regenerating mucosa. It was concluded that the greater histological maturity of the regenerating mucosa may contribute to the lower recurrence rate in colloidal bismuth subcitrate-treated patients than in cimetidine-treated patients. PMID- 1936789 TI - Portal colopathy: prospective study of colonoscopy in patients with portal hypertension. AB - Twenty patients with portal hypertension related to a variety of causes prospectively underwent colonoscopy for hematochezia (n = 10), hemoccult positive stool and anemia (n = 9), or polyp found with screening flexible sigmoidoscopy (n = 2) (includes 1 patient with anemia/heme-positive stool). Twelve patients (60%) had previously undergone a course of sclerotherapy, and 10 (50%) had endoscopic evidence of congestive gastropathy. Colonoscopic findings included mucosal abnormalities resembling multiple vascular ectasias in 14 (70%), 4 of whom also had endoscopic features suggesting a mild, chronic colitis. Neither signs of chronic liver disease nor stigmata suggestive of more severe portal hypertension correlated with the colonoscopic findings. Two patients required heater probe therapy for actively oozing lesions resembling vascular ectasias and an additional two patients sclerotherapy for bleeding midrectal varices. Although likely an overestimate of the frequency, this study suggests that portal colopathy can occur in portal hypertension. Vascular ectasialike lesions in such settings may be associated with acute as well as chronic gastrointestinal bleeding and may require pharmacological, directed endoscopic, or portal decompressive therapy. Additional studies are required to determine not only the pathophysiology but also the true frequency of this entity. PMID- 1936790 TI - Distribution of aneuploid cell populations in ulcerative colitis with dysplasia or cancer. AB - Flow cytometry was used to detect the presence and assess the distribution of aneuploid cell populations in eight proctocolectomy specimens from patients with ulcerative colitis. Mucosal samples were taken according to a systematic protocol for flow cytometry, the surrounding tissue was examined histologically, and the distributions of flow cytometric and histologic abnormalities were "mapped" within each resected colon. Two resection specimens that were negative for dysplasia lacked aneuploid cell populations. Four resection specimens with final case diagnoses of dysplasia or Dukes' stage A carcinoma had 1-5 regions of aneuploidy or increased 4N (G2/tetraploid) cell populations located in discrete areas of the colon. Two specimens with dysplasia or Dukes' stage C carcinoma each had 14-15 different, often overlapping, regions of aneuploidy or increased 4N (G2/tetraploid) cell populations involving large portions of the colonic mucosa. Analysis of the DNA content of the invasive portion of the tumor from the specimen with a Dukes' stage C carcinoma showed a single aneuploid cell population. The results show that single or multiple aneuploid cell populations are often present in colons resected for ulcerative colitis with dysplasia or early cancer. The distribution of these aneuploid cell populations suggests that each represents a clone of cells that has expanded to occupy a discrete region of colonic mucosa. Additional genetic errors may result in multiple aneuploid cell populations that may be associated with an increased risk of developing cancer. These data, therefore, are consistent with the hypothesis that genomic instability and clonal evolution are associated with the progression to dysplasia and carcinoma in ulcerative colitis. Because flow cytometry can measure aneuploid cell populations in colonoscopic mucosal biopsies, it may prove to be complementary to histology for detecting patients with ulcerative colitis who are at risk for neoplastic progression. PMID- 1936792 TI - Prostaglandins and the colonic epithelium. Effects of misoprostol on crypt size, cell production, and cell migration in the dog. AB - Colonic epithelial cell division, cell migration, and cell transit were investigated in dogs given 300 micrograms.kg-1.day-1 of the prostaglandin E1 analogue, misoprostol, for 11 weeks. The animals were then injected with [3H]thymidine and killed at timed intervals. The distribution of labeled and mitotic cells within the crypts was determined by scoring autoradiographs. There were no significant differences in mitotic index or labeling index between the two groups. The data were pooled and converted to give crypt cell production rates of 51.1 +/- 11.1 (control) and 58.24 +/- 8.6 cells per crypt per hour (test). However, the crypt length and cell population were slightly, but significantly, greater in the misoprostol-treated group (P less than 0.01). The movement of the wave of labeled cells with time after injection was used to calculate the median cell migration rates, which were 23.50 +/- 3.03 cell positions per day (control) and 18.30 +/- 2.56 (test). Thus, misoprostol had no significant effect on either the cell migration rate or the transit rates. PMID- 1936791 TI - Mechanisms of acid injury to rabbit esophageal epithelium. Role of basolateral cell membrane acidification. AB - Because mucosal HCl traverses the paracellular pathway before significant damage develops within esophageal epithelium, the effects of mucosal and serosal acidification were compared on Ussing-chambered rabbit esophageal epithelia. Notably serosal, but not mucosal, acidification was associated with cell necrosis, and the latter was accompanied by abolition of potential difference and short-circuit current. The reason for this difference was explored by exposing tissues serosally to ouabain, chloride-free solution, 4-acetamido-4' isothiocyanatostilbene-2-2'-disulfonic acid (SITS), or amiloride. The results show that serosal acidification, but not ouabainization, is associated with cell necrosis and that cell necrosis induced by serosal acidification can be blocked by SITS and chloride-free solution, but not by amiloride. These findings are compatible with the hypothesis that serosal acidification is more damaging than mucosal acidification because of the greater rate with which hydrogen ions can traverse the basolateral membrane; also, the route for more rapid entry appears to involve a SITS-sensitive, chloride-dependent mechanism (e.g., Cl/HCO3 antiport). PMID- 1936793 TI - Morphometry and cell proliferation in endoscopic biopsies: evaluation of a technique. AB - A simple method for the quantification of intestinal epithelial cell proliferation in humans was evaluated. Endoscopic biopsy specimens were stained and microdissected, and the number of mitoses per gland or crypt was determined, as was the area of these units. The technique could readily be applied to tissue from the stomach, small intestine colon, and rectum. The number of mitoses and the size of the proliferative compartments increased caudally from the stomach to the cecum in humans. There was a good correlation between area and mitoses per gland or per crypt (r = 0.89; P less than 0.001), confirming the general equivalence between proliferative rate and compartment size. The method was validated by comparing microdissection-derived data with data previously obtained as part of an autoradiography-based study in the dog. This showed that similar differences in proliferation and crypt cell mass could be obtained but in less than one sixth of the time taken to score autoradiographs. It is concluded that this method for the estimation of gastrointestinal epithelial proliferation correlates well with other well-established techniques, confers speed as well as accuracy, has an all encompassing denominator, and can thus avoid many of the problems associated with the quantification of tissue sections. PMID- 1936794 TI - The role of vasopressin in the pathogenesis of ethanol-induced gastric hemorrhagic erosions in rats. Is vasopressin an endogenous aggressor toward the gastric mucosa? AB - The role of vasopressin in the development of gastric hemorrhagic erosions induced by the oral administration of 1 mL of 75% ethanol in rats was studied. The area of the lesions in homozygous Brattleboro rats, having a defective vasopressin synthesis, was only 20% of that found in Wistar and heterozygous Brattleboro rats, which have normal vasopressin production. It is well known that vasopressin acts via the V1 (pressor) and V2 (antidiuretic) receptors. Administration of V1 and V2 vasopressin-receptor agonists and antagonists in this model showed that pressor-receptor activity is needed for the generation of all lesions in Wistar and heterozygous Brattleboro rats. Ethanol damage to the gastric mucosa was diminished by the V1 antagonist with similar efficacy as in the case of a vasopressin deficiency. Administration of the V1 antagonist and the absence of endogenous vasopressin were shown to protect the deeper layer of the gastric mucosa (assessed by histology) and to reduce significantly the ethanol induced vascular injury and increase in vascular permeability (assessed by the monastral blue technique). Thus, endogenous vasopressin is clearly of great importance in the pathogenesis of gastric hemorrhagic lesions induced by ethanol. These results strongly suggest that vasopressin is an endogenous aggressor toward the gastric mucosa. PMID- 1936795 TI - Central and peripheral control of postprandial pyloric motility by endogenous opiates and cholecystokinin in dogs. AB - The role of endogenous opiates and cholecystokinin (CCK) in the control of postprandial pyloric myoelectric activity was investigated in conscious dogs with chronically implanted intraparietal electrodes at the gastroduodenal junction. Meals consisted of either 20 g/kg of canned food (standard meal) or the same food supplemented with 0.5 mL/kg of arachis oil (fat meal). During the 6 hours after standard and fat meals, the number of pyloric spike bursts, 2-4 seconds in duration, was 61.8 +/- 15.8 and 49.9 +/- 12.7/15 minutes, respectively. Administered 15 minutes before a fat meal, naloxone (50 micrograms/kg IV) decreased the number of spike bursts by 31.4%, whereas methyl-levallorphan, a peripheral opiate antagonist, increased postprandial spike activity by 22.2% when administered IV (0.5 mg/kg) and decreased it when administered intracerobroventricularly at a dose of 10 micrograms/kg. These two antagonists administered in the same conditions before a standard meal had no effect on the postprandial spike activity. A 1-hour infusion of cholecystokinin octapeptide (CCK-8), 500 ng.kg-1.h-1 IV and 50 ng.kg-1.h-1 intracerebroventricularly, performed 1 hour after a standard meal induced a 19.6% and 15.8% decrease in the number of pyloric spike bursts, respectively. Both naloxone IV (50 micrograms/kg) and methyl-levallorphan intracerebroventricularly (10 micrograms/kg) administered before the infusion of CCK-8 reinforced this pyloric inhibition, which was antagonized by methyl-levallorphan IV (0.5 mg/kg). The CCK antagonist asperlicin, 200 micrograms/kg IV and 20 micrograms/kg intracerebroventricularly, administered before a fat meal increased pyloric spike bursts by 22.0% and 31.5%, respectively. These results indicate that after a fat meal, endogenous opiates exert a peripheral inhibitory and central stimulatory control of pyloric motility; they suggest the involvement of both peripheral and central release of CCK. PMID- 1936796 TI - Peptidergic innervation of the human esophageal smooth muscle. AB - Studies were performed to define the peptidergic nature of intramural nerves in the human esophagus. Cryosections of uninvolved surgically resected tissues from 14 individuals were studied by immunofluorescence for the localization of 10 neuropeptides. Myenteric neurons showed bombesin-, calcitonin gene-related peptide-, galanin-, substance P-, vasoactive intestinal polypeptide-, leucine enkephalin-, methionine-enkephalin-, neuropeptide Y-, and somatostatin-like immunoreactivity. Submucous neurons had all the above except neuropeptide Y, methionine-enkephalin, leucine-enkephalin, and bombesin. Both groups of neurons received nerve terminations positive for calcitonin gene-related peptide, galanin, neuropeptide Y, substance P, and vasoactive intestinal polypeptide. Myenteric neurons additionally received terminations positive for neuropeptide Y, methionine-enkephalin, and somatostatin. All muscle layers had varicose fibers that reacted for calcitonin gene-related peptide, galanin, neuropeptide Y, and substance P. Longitudinal and circular muscle received few nerves reactive for leucine-enkephalin, whereas methionine-enkephalin was localized in a few nerve endings in the circular muscle. Somatostatin- and bombesin-reactive nerves occurred in longitudinal muscle. No cholecystokinin-reactive nerves were found. This study extends the results of previous studies and shows the previously undescribed presence of calcitonin gene-related peptide- and galanin-reactive nerves in the human esophagus and identifies neuropeptides that may serve as motor, sensory, and modulatory neurotransmitters of esophageal nerves. PMID- 1936797 TI - Changes in the structure and regeneration mode of the rat small intestinal mucosa following benzalkonium chloride treatment. AB - Tritiated thymidine was administered IP to rats that had been exposed to benzalkonium chloride in the duodenum, jejunum, and ileum, resulting in neuronal ablation. Epithelial cell proliferation and migration were studied 21 and 7 days after treatment. Significant hyperplasia and hypertrophy of the villi and crypts was seen from day 7 on. This was half as pronounced as that of the muscle layer, whose maximal percent increase was not seen until day 21. In the crypt, the proliferation had increased significantly (65% 3H index corrected) and its zone had expanded proportionally to the total crypt depth. After an average of 36 hours in the ileum (48 hours in normal rats), labeled cells reached the tip of the lengthened villi, reflecting significantly accelerated migration. Concerning the distributional pattern of the labeled cells in the crypt, a nonsignificant shift to the lower two thirds of the crypt could be distinguished. From this the author concludes that treatment with benzalkonium chloride influences the proliferation and migration of the epithelial cells in the treated area. These alterations may result from loss of the myenteric plexus, but other factors cannot be excluded. PMID- 1936798 TI - Inversion of the slow-wave frequency gradient in symptomatic patients with Roux en-Y anastomoses. AB - Patients with Roux-en-Y anastomoses may have chronic symptoms of nausea, vomiting, epigastric fullness, and abdominal pain. To investigate the mechanism of these symptoms, the electrical activity of the Roux limb was studied in five symptomatic and four asymptomatic patients with Roux-en-Y anastomoses. Slow-wave and spike activity in the Roux limb were recorded using six bipolar suction electrodes positioned 10 cm apart. Ten healthy volunteers were studied as a control. In the control subjects, the mean slow-wave frequency decreased from 11.27 +/- 0.2 cycles/min at 30 cm below the ligament of Treitz to 10.96 +/- 0.2 cycles/min at 80 cm past Treitz. By contrast, in five patients the slow-wave frequency in the Roux limb increased from 11.12 +/- 0.2 cycles/min 10 cm below the gastrojejunal anastomosis to 11.42 +/- 0.4 cycles/min 50 cm more distally. Four of these five patients had severe symptoms. In the other four patients, of whom three were completely symptom-free, an aborally decreasing slow-wave frequency was observed. In both the controls and the patients with Roux-en-Y anastomoses, the direction of propagation of phase 3 spike bursts of the migrating motor complex was always aboral. During phase 2, most spike bursts were uncoordinated at adjacent recording sites. Propagated spike bursts, single or repetitive, were rare. The propagation direction of these spike bursts was always aboral in healthy controls. In symptomatic patients with inverted slow wave frequency gradients, however, the rare propagated spike bursts always propagated orally. The observed electrical abnormalities may in part be responsible for the symptoms of patients with the Roux-en-Y syndrome. PMID- 1936799 TI - Colonic motility and transit in health and ulcerative colitis. AB - Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P less than 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P less than 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into the sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis. PMID- 1936800 TI - Effect of eating on colonic motility and transit in patients with functional diarrhea. Simultaneous scintigraphic and manometric evaluations. AB - The aim of this study was to correlate colonic motility with transit in 8 patients with functional diarrhea compared to 12 healthy subjects. Intraluminal pressure was measured with perfused catheter ports in the transverse colon, splenic flexure, and descending and sigmoid colons. Transit of the luminal contents was measured by following the movement of 99mTC diethylenetriaminepentaacetic acid instilled as a bolus in the splenic flexure. In patients with diarrhea, the intraluminal marker moved in and out of the transverse and sigmoid colon regions of interest during fasting, unlike healthy subjects, in whom the marker remained in the splenic flexure. After eating, radioactivity immediately increased in both the transverse and sigmoid colons in healthy subjects. In the patients with diarrhea, eating did not alter the marker movement into the different regions of the colon compared with fasting. Within 100 minutes of eating, the intraluminal marker almost disappeared from the regions of interest in patients with diarrhea. Postprandial colonic nonpropagating contractions increased in each region of the colon in healthy subjects; there was only a small postprandial increase in colonic motility in patients with diarrhea. However, the numbers of fasting and postprandial propagating contractions were increased in patients with diarrhea compared with healthy subjects (P less than 0.02). Each propagating contraction moved more tracer in patients with diarrhea than in healthy subjects (P less than 0.05). These studies suggest that (a) in patients with diarrhea, the fluctuation of marker in both transverse and sigmoid colons during the fasting and postprandial periods is associated with decreased nonsegmenting contractions and frequent propagating contractions; and (b) in healthy subjects, the intraluminal marker moved after eating because of a pressure gradient caused by nonpropagating contractions. PMID- 1936801 TI - Quality of life of patients with ulcerative colitis preoperatively and postoperatively. AB - Two instruments, the time trade-off technique and direct questioning of objectives, were used to assign the worth (utility) of the perceived quality of life of patients who had ulcerative colitis requiring surgery. Utilities ranged from 0 to 1 with 0 signifying death and 1 signifying full health. Two groups of patients were studied. Group 1 consisted of 20 patients (14 male and 6 female; mean age, 34.0 +/- 10.3 years) who were studied preoperatively and 1 year postoperatively. The mean preoperative utility was 0.58 +/- 0.34 using the time trade-off technique and 0.38 +/- 0.27 using the direct questioning of objectives. Mean utilities were significantly higher postoperatively, 0.98 +/- 0.07 using the time trade-off technique and 0.88 +/- 0.19 using the direct questioning of objectives (P less than 0.05). Group 2 included 93 patients who had had surgery at least 1 year previously. Twenty-eight had conventional ileostomies, 28 had Kock pouches, and 37 had ileal reservoirs. Mean utilities for these three subgroups ranged from 0.87 +/- 0.18 to 0.97 +/- 0.6. No significant differences were detected among the three subgroups. This study suggests that quality of life is improved after surgery for ulcerative colitis and is high irrespective of the surgical procedure. PMID- 1936802 TI - Perendoscopic manometry of the distal ileum and ileocecal junction in humans. AB - Previous manometric studies of the ileocolonic junction were performed without assessing the precise spatial relationship between recording sensors and ileocolonic junction. In the present study, the motor activity of the ileocolonic junction was recorded using manometric sensors localized under direct colonoscopic control in 11 patients (4 men, 7 women; mean age, 55 years) referred for hematochezia with normal stool frequency. No medications were administered before and during endoscopy. A perfused catheter (OD 1.7 mm, with three side holes 4 mm apart and marked by evenly spaced black rings in the distal 6 cm) was passed through the biopsy channel of the endoscope and advanced through the ileocolonic junction and 6 cm into the ileum. The catheter was then withdrawn into the cecum by 1-cm steps, and motor activity was recorded for 4-6 minutes at each station. A single catheter taped to the endoscope continuously recorded cecal pressure. An ileocecal pressure gradient could not be identified in the majority of subjects; individual values ranged from -8 to +4 mm Hg, and gradients were maintained over the entire length of the ileum. In the distal ileum, tonic and phasic pressure waves were detected. Tonic variations were present for 70.1% of the recording time, either alone (44%) or together with phasic waves (56%). Phasic waves were present for 10.3% of the recording time and, according to their duration, were subdivided into those compatible with the rate of ileal slow waves and prolonged waves not compatible with the rate of ileal slow waves. Regular phasic waves could be either isolated or in clusters; prolonged waves were always isolated. A similar proportion of regular (27.9%) and prolonged (31.2%) phasic waves propagated aborally along the ileum or from ileum to cecum. Clusters presented an average of 8.7 +/- 0.6 peaks/min, and 44% of them propagated aborally. The manometric characteristics did not vary between the segments 5-3 cm and 2-0 cm proximal to the ileocecal junction. In conclusion, a powerful ileocecal sphincter was not detected at the human ileocecal junction, and motor activity of the distal ileum was characterized by tonic changes and rapid phasic contractions. PMID- 1936803 TI - Delayed gastrointestinal transit times in anorexia nervosa and bulimia nervosa. AB - Anorectic and bulimic patients frequently report symptoms of constipation, bloating, and abdominal pain suggestive of abnormal gastrointestinal motility or transit. However, except for studies of gastric emptying, gastrointestinal motility and transit in these eating disorders have not been investigated. Ten anorectic and 18 bulimic inpatients were compared with 10 healthy controls. Whole gut transit was tested by the radiopaque marker technique, and mouth-to-cecum transit time was assessed by the lactulose breath test. All anorectics and 67% of bulimics complained of constipation. Whole-gut transit time was significantly delayed in both anorectics (66.6 +/- 29.6 hours) and bulimics (70.2 +/- 32.4 hours) compared with controls (38.0 +/- 19.6 hours). Mouth-to-cecum transit time also tended to be longer in anorectics (109.0 +/- 33.5 minutes) and bulimics (106.2 +/- 24.5 minutes) than in controls (84.0 +/- 27.7 minutes), but these differences were not statistically significant. Delayed transit could contribute to or perpetuate the eating disorders by (a) causing the patient to feel bloated, thereby exacerbating fear of fatness, or (b) causing rectal distention, which may reflexly inhibit gastric emptying. PMID- 1936804 TI - Ultrasonic tissue characterization of chronic liver disease using cepstral analysis. AB - To evaluate the morphological changes in chronic liver disease by means of ultrasonography, cepstral analysis was applied to the ultrasonic waveforms obtained with a 10-MHz transducer during peritoneoscopy. Assuming that liver tissue was a collection of semiregularly arrayed small scatters of ultrasound, the spaces between scatterers of the liver could be measured by means of cepstral analysis. From the distribution of the spaces between scatterers, two statistical parameters, mode and kurtosis, were determined for each patient. The mode of spaces between scatterers for liver cirrhosis was significantly larger than that for chronic hepatitis and nonspecific change. The mode of spaces between scatterers was correlated with the size of hepatic lobules or nodules. The kurtosis of spaces between scatterers for chronic hepatitis and liver cirrhosis was significantly smaller than that for nonspecific change. As a preliminary study for noninvasive application of this technique, cepstral analysis was also applied to the ultrasonogram obtained through the abdominal wall with a 3.5-MHz transducer. The results obtained with a 3.5-MHz transducer were correlated well with those obtained with a 10-MHz transducer. These results suggest the possibility of noninvasive evaluation of the structural changes in chronic liver disease. PMID- 1936805 TI - Treatment of primary biliary cirrhosis with low-dose weekly methotrexate. AB - Nine women with symptomatic precirrhotic primary biliary cirrhosis have been treated with oral pulse methotrexate, 15 mg/wk, for 12-34 months. Three women had pruritus, two fatigue, and four pruritus and fatigue. Itching disappeared and fatigue lessened or disappeared in all within 4-11 months after starting methotrexate. All who itched were able to discontinue cholestyramine (five) or antihistamines (two). Biochemical tests of liver function improved in all patients and then worsened in three when methotrexate was discontinued or the dose lowered. Mean serum alkaline phosphatase decreased from 471 to 171 U/L (P less than 0.01), serum bilirubin from 0.99 to 0.59 mg/dL (P less than 0.05), and serum alanine aminotransferase from 132 to 61 U/L (P = 0.02), and serum cholesterol fell from 265 to 213 mg/dL (NS). The decrease in serum cholesterol was significant, P = 0.05, if data were used just from the six women whose baseline serum cholesterol levels were elevated. Serum albumin remained normal in all. The serum bilirubin levels became normal in three of four patients with elevated levels. The serum alkaline phosphatase levels became normal in four patients and the alanine aminotransferase levels in three. Liver histology improved in five patients and was stable in the remaining four based on a quantitative evaluation of coded liver biopsy specimens. The improvement in histology was primarily due to decreased portal inflammation and bile duct injury. The titer of antimitochondrial antibody decreased in seven patients. The data suggest that methotrexate may be effective treatment for precirrhotic primary biliary cirrhosis. Controlled trials are needed to evaluate long-term efficacy and toxicity. PMID- 1936806 TI - Effectiveness of a purified human hemoglobin as a blood substitute in the perfused rat liver. AB - The efficacy of purified cross-linked human hemoglobin solution in maintaining the metabolic integrity of perfused livers from fed rats was determined and compared with that of livers recirculated with red blood cells, perfluorocarbon, and Krebs' Ringer bicarbonate buffer media at normal and accelerated flow rates. The data indicate that oxygen utilization was comparable in livers perfused with red blood cell medium (53.5 +/- 4.0 microL.g liver-1.min-1), hemoglobin (45.7 +/- 1.9), and perfluorocarbon (57.2 +/- 6.1) and less in livers perfused with Krebs' Ringer bicarbonate buffer solution at normal (17.4 +/- 1.4) and high (27.7 +/- 1.4) flow rates. Bile flow, the outflow of glucose and lactic acid, and residual glycogen levels were similar when livers were perfused with red blood cells (hematocrit, 19) and hemoglobin solutions containing 7 g hemoglobin/dL at flow rates of 1.1-1.2 mL.g liver-1.min-1. However, livers perfused with perfluorocarbon at 1.1 mL.g-1.min-1 showed a significantly greater (P less than 0.01) decline in bile flow and outflow of glucose and lactic acid. Livers perfused with Krebs' Ringer bicarbonate buffer at normal (1.3 mL.g-1.min-1) and accelerated flow rates (3.0 mL.g-1.min-1) also showed a progressive decrease in bile flow and marked glycogenolysis as well as depletion of adenosine triphosphate content. In addition, morphological studies (light and electron microscopy) showed more vacuoles, membrane alterations, and increased mitochondrial swelling in livers perfused with Krebs' Ringer bicarbonate buffer and perfluorocarbon. These findings suggest that hepatocyte function in livers from fed rats is maintained equally well with hemoglobin solutions and with red blood cell medium, suggesting that cross-linked hemoglobin solution may serve as an effective blood substitute for maintaining adequate oxygenation and metabolic integrity of the isolated perfused rat liver. PMID- 1936807 TI - Abnormal sympathetic and renal response to sodium restriction in compensated cirrhosis. AB - It has been proposed that in liver cirrhosis portal hypertension causes splanchnic vasodilation and this induces blood volume expansion to maintain blood pressure. The current study was designed to explore the homeostatic response to sodium restriction, a maneuver aiming to contract blood volume, in compensated cirrhosis. Mean blood pressure, sympathetic nervous activity, and proximal sodium reabsorption were evaluated in 16 healthy control and 21 nonazotemic cirrhotic patients (11 without ascites and 10 with ascites) under two experimental conditions: after 4 days on a free sodium diet (basal condition) and after 4 days on a restricted sodium diet (40 mmol/day). No differences were observed in basal conditions in the above parameters between control and cirrhotic patients without ascites. However, cirrhotic patients with ascites showed lower basal values of mean blood pressure and higher basal levels of both plasma norepinephrine and fractional proximal sodium reabsorption than controls. Neither control nor cirrhotic patients with ascites showed significant changes in the measured parameters after sodium restriction. In contrast, in nonascitic patients, this maneuver induced an elevation in plasma norepinephrine concentration (164.4 +/- 24.6 vs. 270.1 +/- 24.9 pg/mL; mean +/- SEM; P less than 0.005) and in fractional proximal sodium reabsorption (86.4 +/- 2.1 vs. 91.8% +/- 0.5%; P less than 0.01). In addition, the nonascitic cirrhotic patients became hypotensive compared with controls (80.9 +/- 1.6 vs. 88.5 +/- 4.8 mm Hg; P less than 0.05) when subjected to the low-sodium diet. In patients without ascites, under conditions of sodium restriction, the decrease in mean arterial pressure correlated inversely with the increase in plasma norepinephrine concentration (r = -0.713; P less than 0.05), whereas the levels of plasma norepinephrine correlated directly with fractional proximal sodium reabsorption (r = 0.893; P less than 0.01). These findings suggest that ineffective circulatory volume is detected in nonascitic cirrhotic patients only under conditions of sodium restriction, but it is always present in cirrhotic patients with ascites, irrespectively of the amount of sodium in the diet. These results are compatible with the existence of fixed arterial vasodilation in cirrhosis. PMID- 1936808 TI - HLA DRw8 and complement C4 deficiency as risk factors in primary biliary cirrhosis. AB - HLA class I, II, and III alleles were investigated in 25 consecutive unrelated German patients with primary biliary cirrhosis and in two families with two primary biliary cirrhosis patients in each. In primary biliary cirrhosis patients, HLA class I antigens did not differ significantly from in health controls. For HLA class II antigens, a highly significant increase of HLA DRw8 was found in patients with primary biliary cirrhosis compared with controls. Thirty-six percent vs. 3.6% were DRw8 positive [relative risk = 15.28; P (corrected) = 0.00013]. The genetic typing of HLA class III alleles revealed an increased incidence for C4AQ0 alleles [72% vs. 34.5%, relative risk = 4.89: P (corrected) = 0.0056]. A highly significant proportion of primary biliary cirrhosis patients carrying both DRw8 and C4A-Q0 alleles (relative risk = 183.75; P = 9.7 x 10(-7)) were found. In one family, a mother and her daughter had primary biliary cirrhosis, both sharing the major histocompatibility complex haplotype HLA-A1, -B8, -DR3, -C4AQ0B1. In the other family, two sisters with primary biliary cirrhosis shared the major histocompatibility complex haplotype HLA-A24, -B8, -DRw8, -C4A4B2. These studies contribute to the further elucidation of the immunogenetic background of primary biliary cirrhosis. PMID- 1936809 TI - Risk factors for septicemia following endoscopic biliary stenting. AB - The purpose of this study was to identify patients who were more likely to experience septicemia after endoscopic biliary drainage. In an attempt to determine the relative importance of each risk factor and their possible interdependancy to more precisely identify high-risk patients and to deduce some guidelines for prevention, a discriminant regression analysis of risk factors for septicemia was used. Clinical, biological, and radiological data of 34 consecutive patients who experienced septicemia within 3 days after endoscopic biliary stenting were reviewed retrospectively and compared with data of a group of 71 patients without any septic complication. If only data available before the procedure were used in the discriminant analysis, prior cholangitis and leucocytosis appeared as significant risk factors, but the linear combination of these data could not predict septicemia in 50% of cases. When information concerning the quality of drainage after the procedure was introduced into the analysis, 91% of the septicemic patients were identified, and other expected risk factors such as the nature of the stricture, the type of drainage, or prior cholangitis and leukocytosis had no or marginal predictive values. Patients referred from centers where duodenoscopes might have been poorly disinfected appeared to be at higher risk for Pseudomonas aeruginosa septicemia. These results emphasize the crucial role of the quality of drainage as a risk for septicemia. Regarding the prevention of infection, it is concluded from this study that (a) pure diagnostic endoscopic retrograde cholangiopancreatography should be avoided in obstructed patients if drainage cannot be performed during the same procedure; (b) drainage should be as complete as possible; (c) antibiotics should be administered before ERCP to every patient with suspected obstructive jaundice and should cover P. aeruginosa if local epidemiological data suggest that there is a problem with disinfection of the endoscopes; and (d) the quality of drainage should guide the duration of antibiotic prophylaxis. PMID- 1936810 TI - Portal and biliary phases of enterohepatic circulation of corrinoids in humans. AB - The assimilation of labeled cobalamin and the transport of corrinoids in portal blood, peripheral venous blood, and bile were studied in eight cholecystectomized patients, after ingestion of a dose of cyano[57Co]cobalamin (0.5 microCi). The radioactivity appeared in the portal vein after a delay of 1.5-2 hours and in the peripheral vein 1 hour later. In bile, it reached a maximum at 24-72 hours; the excreted cobalamin corresponded to 1.42% +/- 0.92% of the dose ingested. The output of total corrinoids was 1.85 nmol/day. The high-performance liquid chromatography analysis of bile showed the presence of methylcobalamin, 5' deoxyadenosylcobalamin, hydroxocobalamin, and an unknown corrinoid. This corrinoid bound to R binder but not to the intrinsic factor, and it had the same retention time as cobinamide. The R binder was the single cobalamin-binding protein found in bile. It was completely saturated in some periods of bile secretion. The corrinoids corresponding to such a period were eluted in Sephacryl S 300 gel filtration (Pharmacia Fine Chemicals, Uppsala, Sweden) in two peaks corresponding to saturated R binder and to free cobalamin. The mean level of total corrinoid was significantly higher in the portal vein (593 +/- 238 pmol/L) than in the peripheral vein (376 +/- 114 pmol/L) (P less than 0.01). This "cobalamin analogue" fraction was hypothetical because it was calculated from the difference between total corrinoid concentration and the so called "true cobalamin" concentration. This difference corresponded to the cobalamin analogue fraction. These data show that bile removes not only cobalamin but also cobalamin analogues and that R binder is the single carrier protein involved in their excretion. PMID- 1936811 TI - Significance of computed tomography for shock-wave therapy of radiolucent gallbladder stones. AB - One hundred eleven symptomatic patients (91 women, 20 men) with solitary "radiolucent" stones (proved by a plain radiograph) underwent examination with computed tomography for stone analysis before extracorporeal shock-wave lithotripsy with a second-generation piezoelectric lithoptripter. The aim of the study was to assess the importance of computed tomography as a diagnostic pretreatment procedure compared with the plain abdominal radiograph: computed tomography density values greater than 50 Hounsfield units (HU) were found in 64 of 111 patients with radiolucent stones (58%). Of these 64, 50 patients even had values greater than 90 HU (50/111;45%). The majority of the stones with density values greater than 50 HU had a hyperdense rim (43 of 64) with a mean maximum attenuation of 134 +/- 68 HU. A significantly higher degree of stone disintegration was achieved with stones of group A (less than or equal to 50 HU) than with those in group B (greater than 50 HU and less than or equal to 90 HU) and group C (greater than 90 HU) with respect to the mean maximum fragment size after the first (P less than 0.001) and last (P less than 0.01) lithotripsy and with respect to the total number of shock waves applied (P less than 0.001) and the number of treatments (P less than 0.001). No difference was observed between groups B and C. After all follow-up periods, the rate of complete stone disappearance was higher in group A than in group B (NS for 1, 2, and 4 months of follow-up; P less than 0.01 for month 8; P less than 0.05 for month 12) and group C (P less than 0.05 for 1, 2, and 4 months of follow-up; P less than 0.001 for months 8 and 12). The authors conclude that computed tomographic analysis of gallstones before lithotripsy is more sensitive in detecting nonradiolucent stones than in the plain radiograph. Computed tomographic stone analysis seems to provide a better selection of patients suitable for biliary lithotripsy and could become a standard diagnostic pretreatment procedure to improve stone disintegration and complete stone disappearance after shock-wave lithotripsy and adjuvant chemolitholysis. PMID- 1936812 TI - Postinfantile giant cell hepatitis in association with hypereosinophilia. AB - Fatal giant cell hepatitis and hypereosinophilia developed in a 39-year-old man. The coexistence of these two rare disorders has not been previously described. Despite extensive testing, no specific causes could be identified. Evidence for a viral etiology of some cases of giant cell hepatitis is briefly reviewed. PMID- 1936813 TI - Idiopathic neonatal iron-storage disease. AB - A 21-day-old infant presented with anemia, conjugated hyperbilirubinemia, hypoproteinemia, and a severe coagulopathy. The hospital course was marked by progressive hepatic failure, encephalopathy, and renal insufficiency. The infant died on day 15 of hospitalization. Postmortem examination showed diffuse hepatic fibrosis and marked siderosis of the liver, pancreas, kidney, adrenal glands, and the duodenal epithelium, with sparing of the reticuloendothelial system. These findings were characteristic of idiopathic neonatal iron-storage disease. Previously reported cases are summarized and discussed. An increased awareness and understanding of this rapidly fatal disorder will be important for genetic counseling and possibly in defining an aberrant mechanism in the handling of iron. PMID- 1936814 TI - Cholecystokinin-mediated ileal electrolyte transport in the guinea pig. Characterization of receptor subtype. AB - Cholecystokinin (CCK) receptors are currently divided into at least two subtypes: a CCK-A subtype, responsive to the sulfated form of cholecystokinin octapeptide (CCK-8) and selectively antagonized by L-364,718, and a CCK-B subtype, which shares equal affinities for gastrin and CCK-8. In the present study the receptor subtype that mediates guinea pig ileal secretion by evaluating the potencies of CCK- and gastrin-related peptides to evoke increases in transmucosal short circuit current was characterized. The antagonist potencies of L-365,260 (CCK-B selective) and L-364,718 (CCK-A selective) against CCK-8 were also determined. Both CCK-8 and cerulein, when added to the serosal side of the tissue, evoked increases in the short-circuit current, having EC50 values of 0.8 and 0.2 nmol/L, respectively. Desulfated (SO3) CCK-8, CCK-4, gastrin17-I, pentagastrin, gastrin17 II, and gastrin13-I were relatively weak agonists (EC50 greater than 1000 nmol/L. Cholecystokinin octapeptide-induced short-current responses were competitively antagonized by L-364,718 (pA2, 10.3) and L-365,260 (pA2, 7.4). The high selectivity of the tissue for sulfated CCK-8 suggests that the secretory effect of CCK-8 on guinea pig ileal electrolyte transport is mediated by a CCK-A receptor. The potent effect of L-364,718 against CCK-8 is also consistent with an action at the A-subtype receptor. PMID- 1936816 TI - Methotrexate therapy of primary biliary cirrhosis: promising but worrisome. PMID- 1936815 TI - Recurrent gastrointestinal bleeding associated with myelofibrosis and diffuse intestinal telangiectasias. PMID- 1936817 TI - Transforming growth factors in human chronic hepatitis and cirrhosis: correlations with fibrogenesis and hepatic regeneration. PMID- 1936818 TI - H2 antagonists by continuous infusion: i.v. or i.g.? PMID- 1936820 TI - Role of fructose-sorbitol malabsorption in the irritable bowel syndrome. PMID- 1936819 TI - Functional bowel disease: the role of fructose and sorbitol. PMID- 1936821 TI - Helicobacter pylori infection and inflammation of the gastric corpus. PMID- 1936822 TI - Postparacentesis plasma expansion prevents asymptomatic laboratory abnormalities, but does it have any impact on morbidity or mortality? PMID- 1936823 TI - Cancer risk in left-sided colitis. PMID- 1936824 TI - Stress ulcer prophylaxis. PMID- 1936825 TI - The use of 6-mercaptopurine in adolescents with Crohn's disease. PMID- 1936826 TI - Pancreatic ductal stones: frequency of successful endoscopic removal and improvement in symptoms. AB - Pancreatic ductal stones may be responsible for attacks of acute pancreatitis (chronic relapsing pancreatitis) or exacerbations of chronic pain in patients with chronic pancreatitis. This study was undertaken to identify those patients with predominantly main pancreatic duct stones most amenable to endoscopic removal and to determine the effects on the patients' clinical course with such removal. Thirty-two patients with ductographic evidence of chronic pancreatitis and pancreatic duct stones underwent attempted endoscopic removal. Of the patients, 71.9% had complete or partial stone removal and 67.7% improved after endoscopic therapy. Symptomatic improvement was most evident in the group of patients with chronic relapsing pancreatitis. Factors favoring stone removal included (1) three or less stones, (2) stones confined to the head and/or body of the pancreas, (3) absence of a downstream stricture, (4) stone diameter less than or equal to 10 mm, and (5) absence of impacted stones. After successful stone removal, 25% of patients had regression of the ductographic changes of chronic pancreatitis and 41.7% had a decrease in the main pancreatic duct diameter. The only complication from therapy was mild pancreatitis in 8.2%. These data suggest that removal of pancreatic duct stones may result in symptomatic improvement. A longer follow-up will be necessary to determine whether endoscopic success results in long-standing clinical improvement and/or permanent regression of the morphologic changes of chronic pancreatitis. PMID- 1936827 TI - Needle knife papillotomy for endoscopic sphincterotomy and cholangiography. AB - Needle knife papillotomy (NKP) was used to achieve diagnostic endoscopic cholangiography in 39 patients and endoscopic sphincterotomy in 24 patients when conventional endoscopic methods had failed. These patients represent 2.2% (cholangiography) and 4.2% (sphincterotomy) of the total number of patients undergoing these procedures during the same period. Cholangiography was achieved in 37 of 39 patients and sphincterotomy was successfully accomplished in all 24 patients with the assistance of NKP. Complication rates of 2.5% for cholangiography and 12% for sphincterotomy are higher than our own rates for non NKP-assisted procedures, but the clinical benefits obtained were considered to outweigh these increases or the risks of alternative procedures. NKP is an effective endoscopic tool, allowing endoscopic sphincterotomy to be performed when conventional techniques fail. In addition, in carefully selected cases, NKP is helpful in allowing diagnostic cholangiography when other endoscopic methods fail. PMID- 1936828 TI - ERCP in the diagnosis of extrahepatic biliary atresia. AB - This study assessed the usefulness of ERCP in the diagnosis of biliary atresia. We evaluated 57 infants with prolonged cholestasis with abdominal ultrasound, liver biopsy, and ERCP. Using clinical observations alone, 22 infants were thought to have biliary atresia; whereas 35 children were thought to have neonatal hepatitis. The ERCP was performed with a prototype duodenoscope and was successful in all infants except two with biliary atresia. In 20 infants three types of radiological findings consistent with biliary atresia were seen: type 1, no visualization of biliary tree (35%); type 2, opacification of the distal common duct and gallbladder without visualization of the main hepatic duct (35%); and type 3, opacification of the distal common duct, the gallbladder, and a segment of the main hepatic duct with biliary lakes at the porta hepatis (30%). Twenty-five of 35 infants with suspected neonatal hepatitis were excluded because of a liver biopsy that was diagnostic. In the remaining 10 infants the liver biopsy had some features of extrahepatic biliary atresia and ERCP was performed prior to surgery. A normal extrahepatic biliary tree was obtained in all of them. In conclusion, ERCP permits the visualization of the biliary tree in young infants and is useful in selecting those infants who should be considered for exploratory laparotomy. PMID- 1936829 TI - Comparison of endoscopic forceps biopsies and capsule biopsies in determining disaccharidase activity in the duodenum. AB - Endoscopic biopsy is an accepted technique for obtaining samples of small bowel mucosa for histological examination. In this study a comparison between endoscopic forceps biopsies and capsule biopsies in estimating disaccharidase enzyme activity in the small bowel was evaluated. Disaccharidase levels on 168 consecutive small bowel biopsies obtained by either endoscopic biopsy or capsule biopsy were reviewed retrospectively. There was no significant difference in enzyme activity in samples collected by either method. Another 18 patients had simultaneous endoscopic and capsule biopsies from the second part of the duodenum. Again, there was no difference in enzyme activity between samples collected by either technique at the same level in the duodenum. The disaccharidase activity in forceps biopsies taken from the second part of the duodenum is equivalent to those obtained by capsule biopsy. PMID- 1936830 TI - Barium enema versus colonoscopy for patients with polyps found during flexible sigmoidoscopy. AB - This prospective study compares the accuracy of barium enema examination performed by experienced radiologists to colonoscopy performed by experienced gastroenterologists blinded to the radiographic findings to detect proximal, synchronous lesions in patients with polyps detected during fiberoptic sigmoidoscopy. Three thousand six patients were examined, of whom 147 (5%) had polyps larger than 0.5 cm in diameter. Of 114 patients who completed the protocol, 46 patients (40%) had synchronous, proximal colonic lesions. There were no radiographic false positives, but the single-contrast barium enema missed polyps in 13 while detecting polyps in 2 patients (sensitivity = 13%). The double contrast barium enema missed proximal polyps in 23 patients while detecting them in 8 (sensitivity = 26%). We conclude that patients with neoplastic polyps found during fiberoptic sigmoidoscopy should have colonoscopy without barium enema. If the entire colon cannot be examined at colonoscopy, we advise double-contrast barium enema. PMID- 1936831 TI - Endoscopic features of gastric carcinoids. AB - Endoscopic findings were studied in eight patients with gastric carcinoid tumors. Five patients had a single tumor and the remainder had multiple tumors. Endoscopic examinations revealed smooth, submucosal masses rounded in shape in all patients. In six patients, the lesion was accompanied by an irregularly shaped erythematous depression or ulceration, which was considered to be a characteristic endoscopic finding of gastric carcinoid. An accurate preoperative diagnosis was made in six patients by endoscopy in combination with biopsy. PMID- 1936832 TI - Endoscopic ultrasonography in rectal carcinoid tumors: contribution to selection of therapy. AB - To assess the clinical value of endoscopic ultrasonography (EUS) in carcinoid tumors of the rectum, we studied endoscopic and EUS findings in five patients whose tumors were relatively small in size. Endoscopy revealed sessile or semi pedunculated smooth elevations, with mucosa of normal appearance. The elevations ranged from 5 to 15 mm in diameter, and were yellowish to white in color. EUS failed to demonstrate a small tumor in two patients whereas in the remaining three patients, a homogeneously hypoechoic mass, which was restricted to the submucosal layer, was detected. All patients were treated by endoscopic excision or local resection of the tumor, which resulted in complete removal of the tumor. We believe that even though EUS is not efficacious in cases of very small carcinoid tumors of the rectum, it can provide clinically important information in choosing therapy. PMID- 1936833 TI - Addition of senna improves colonoscopy preparation with lavage: a prospective randomized trial. AB - Attempts have been made to further improve the widely performed colonoscopy preparation with lavage. In a prospective study, 120 outpatients and inpatients scheduled for total colonoscopy were randomized to two preparatory regimens. The day before endoscopy either extractum sennae (N = 60) or a placebo solution (N = 60) was given. Just before examination all patients underwent whole gut irrigation with a polyethylene glycol electrolyte lavage solution (PEG-ELS). Adequacy of preparation, patient tolerance, and the necessary amount of PEG-ELS were assessed. Physician assessment of colon cleansing showed superiority in the group with additional laxative. The colon was free of solid debris in 66.7% of patients after PEG-ELS and in 90% after senna/PEG-ELS administration (p less than 0.01). Patient tolerance was similar in both groups with 86.7% vs. 83.3% of subjects rating the preparation as tolerable. Severe adverse events were not observed. In the senna/PEG-ELS group, significantly less (p less than 0.05) lavage fluid was needed. We conclude that the combination of senna and PEG-ELS is more effective than PEG-ELS in cleansing the colon for colonoscopy. PMID- 1936834 TI - Cytological brushing urea broth test: a highly sensitive and specific test for Helicobacter pylori infection. PMID- 1936835 TI - Marked endoscopic gastrostomy tubes permit one-pass Ponsky technique. PMID- 1936836 TI - A new guidewire technique for biliary strictures. PMID- 1936837 TI - Gastric carcinoma spread to the duodenum. PMID- 1936838 TI - Endoscopic identification of a new gastric pigment with characterization by energy dispersive x-ray analysis. PMID- 1936839 TI - Complete dysphagia resulting from structural fatigue of an esophageal endoprosthesis. PMID- 1936840 TI - Transient complete esophageal obstruction after pneumatic dilation of the lower esophageal sphincter for achalasia. PMID- 1936841 TI - Dilation of achalasia in the young: a useful alternative. PMID- 1936842 TI - Endoscopic findings in Henoch-Schonlein purpura. PMID- 1936843 TI - Successful treatment of post-operative pleurobiliary fistula by endoscopic technique. PMID- 1936845 TI - Biliary stents: use and abuse. PMID- 1936844 TI - Helicobacter pylori and the endoscopist: whether to diagnose. PMID- 1936846 TI - Calculus formation around common bile duct stents: a complication of long-term biliary drainage. PMID- 1936847 TI - Breakage of an endoscopically placed bile duct stent. PMID- 1936848 TI - Percutaneous endoscopic removal of an impacted cystic duct stone. PMID- 1936849 TI - A simple method for PEG tube removal. PMID- 1936850 TI - Unusual complication of naso-enteric feeding tube. PMID- 1936851 TI - Endoscopic evidence of gastric mucosal prolapse with retching and vomiting. PMID- 1936852 TI - Barium granuloma of the rectum. PMID- 1936853 TI - Inverted sigmoid diverticulum: a misleading polyp. PMID- 1936854 TI - Duodeno-pancreatico-choledochal rupture of pseudocyst. PMID- 1936855 TI - Colonic arterial spider in cirrhosis. PMID- 1936856 TI - A new twist to situs inversus. PMID- 1936857 TI - Spontaneous partial elimination of a carcinoma of the esophagus. PMID- 1936858 TI - [The difficulties in dealing with sterility]. AB - In this article we describe the specific psychological situation of the sterile couple. Especially the interaction within the couple on one hand and that between the couple and the therapist on the other are reflected as an expression of transference phenomena. These phenomena are explained and "ways out of the dilemma" are shown. PMID- 1936859 TI - [Blood flow in the umbilical vein and artery in pregnancy]. AB - Transplacental gas exchange and supply of nutritive substances to the foetus is guaranteed by an increase of umbilical blood flow (Qnv). It was investigated, whether the umbilical blood flow (Qnv) is influenced by physiological conditions during pregnancy and if changes occur in the umbilical blood flow velocity wave forms. In this study, 31 pregnant women between the 24th to 40th week of gestation were examined with a pulsed wave duplex scanner ADR Kranzbuhler 8150. The mean flow velocity (Vnv) of the umbilical vein and the diameter of the vessel were parameters, which were included in the calculation of the umbilical blood flow. The flow profile of the umbilical artery allowed determination of the maximum systolic frequency (Fmax) and the end-diastolic frequency (Fmin). Based on these data, three indices--RI, PI, S/D ratio were calculated. The blood flow of the umbilical vein (Qnv) shows a linear increase up to the 36th week of gestation and remains at this level thereafter. The increase of umbilical blood flow (Qnv) is mainly caused by an increase of the diameter of the umbilical vein (81%, 26th-40th week of gestation) and to a lesser degree by an increase of the mean flow velocity (Vnv) (18%, 26th-40th week of gestation). The diameter of the vein is highly correlated both with the foetal birth weight (r = 0.60) and the umbilical blood flow (Qnv) (r = 0.73). Throughout pregnancy, flow velocity waveforms showed significant changes of the maximum systolic frequency (Fmax) from 973 Hz (SD 128 Hz; 26th week of gestation) to 1130 Hz (SD 152 Hz; 40th week of gestation) and an increase of the end-diastolic frequency (Fmin) from 246 Hz (SD 58 Hz; 26th week of gestation) to 423 Hz (SD 91 Hz; 40th week of gestation). The higher increase of the end-diastolic frequency (Fmin) results in a decrease of the resistance index (RI), pulsatility index (PI) and SD-ratio. None of the investigated cases showed an end-diastolic frequency (Fmin) of less than 200 Hz. These results reveal, that determination of the blood flow of the umbilical vein mainly depends on measuring the diameter of the vessel rather than on measurements of the blood flow velocity (Qnv) of the vein. With the presently available equipment, accurate measurements of the diameter are very difficult. The increase of blood flow of the umbilical vein is not proportional to the foetal growth; moreover, it remains constant from the 36th week of gestation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1936860 TI - [Pathologic Doppler flow findings and cardiotocography results]. AB - Of 1950 pregnant patients (2870 Doppler ultrasound measurements) we observed, in a study group with highly abnormal Doppler-flow findings (n = 66, Feb. 1990), a correlation of Doppler flow and FHR-recordings. Among these 66 patients we retained 60 (91%) in the hospital. They had at least 2 FHR-recordings a day. The results of Doppler flow measurements in the fetal aorta and umbilical artery correlated well with diagnosis of IUGR. The comparison of the overall results of both fetal vessels did not indicate any significant difference. In 21% of all patients with highly abnormal Doppler flow findings, was no abnormal FHR record until delivery. 26% already showed an abnormal non-stress test before the first pathological Doppler assessment, in 44% abnormal FHR-recordings were observed later than the first abnormal Doppler flow finding in the course of pregnancy. The median interval was 13.5 days in cases with increased Doppler flow parameters but with detectable end-diastolic blood flow and was reduced to 8 days in cases with absent end-diastolic blood flow. In 9% of all cases, abnormal results were found with both methods on the same day. In 32% we observed a reproducible notch in Doppler flow velocimetry of uteroplacental vessels. The rate of congenital malformations was 14%. Thus abnormal Doppler flow signals can be estimated as "early" prognostic criterias for a compromised fetus at risk. PMID- 1936861 TI - [Clinical significance and fetal outcome in end-diastolic decreased flow in the umbilical artery and/or fetal aorta: analysis of 51 cases]. AB - The AEDV in the umbilical artery or the foetal aorta is considered to be the most severe waveform abnormality. Using pulsed Doppler, we found such a waveform in 51 foetuses out of 954 high-risk pregnancies (33/51 in both vessels, 17/51 aorta only and 1/51 umbilical artery only). A reverse flow was registered in 24 foetuses. The outcome was compared with that of a control group (n = 72) showing normal Doppler findings. The following parameters were highly significant (p less than 0.001): Rate of Caesarean section owing to foetal distress (85.3% to 4.8%), of growth retardation (IUGR) (66.7% to 6.0%), of premature delivery (73.5% to 7.5%), of low postnatal pH- and Apgar score (73.5 to 12.1%), of admission to the neonatal intensive care unit (94.1% to 8.6%), of morbidity (35.3% to 2.3%) and of mortality (41.1% to 0%). We observed 17/51 intrauterine and 4/51 postnatal deaths. The rate of malformations was 35.3% with 4 cases of aneuploidy. Considering the malformations, the rate of corrected mortality was 23%. We found, that the association of an AEDV and the absence of severe IUGR is highly suspicious of malformation. We also observed, that congenital heart diseases (CHD) could lead to an AEDV too. An AEDV precedes a pathological cardiotocogram (CTG) with a latency of 0 to 35 days (mean 9.5 days). This latency is not predictable, but we think, that a reliable assessment of jeopardy is possible by analysing further vessels (Aa. arcuatae, A. renalis, A. carotis interna): 72.5% of the foetuses with AEDV had high indices in the carotid artery and 93.1% among these showed a pathological CTG pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936862 TI - [Comparison of biochemical and Doppler sonographic monitoring of high-risk pregnancies]. AB - We performed in 113 patients at least three simultaneous determinations of serum HPL and oestriol in 24-hour urine samples, as well as Doppler flow studies at the arcuate artery (AA), umbilical artery (UA), foetal aorta and internal carotid, because of suspicion of IUGR. The diagnostic value was studied with regard to IUGR, placental weight and mode of delivery. Concerning the detection of IUGR, the superiority of Doppler parameters (AA, UA) is shown. In the total number of patients, the rates for sensitivity and specificity for UA (78/91%) and AA (58/89%) exceed the hormone parameters. Oestriol, in particular, (13/63%) shows a marked difference, but even HPL (37/63%) cannot compete with respect to diagnostic value. PMID- 1936863 TI - [Doppler flow changes in maternal and fetal blood vessels before and during peridural anesthesia]. AB - 26 women with an uneventful singleton pregnancy near term underwent scheduled Caesarean section with lumbar epidural anaesthesia (PDA). Doppler-flow measurements of the foetal umbilical artery and the maternal hypogastric artery were taken before and after sympathicolysis was established. The mean arterial blood pressure was maintained unchanged between the measurements. Both measurements were performed by the same examiner. Three patients received additional general anaesthesia during the operation because of inadequate analgesia. The resistance index (RI) with PDA decreased significantly in 23 patients by a mean of 7.6% (p less than 0.05). The RI in those patients (n = 3) with inadequate analgesia increased by a mean of 27%. The physiologically reversed diastolic flow in the maternal hypogastric artery was mathematically taken into consideration by applying the quotient of the systolic flow and the diastolic reversed flow (V/R-quotient). The V/R-quotient increased with established sympathicolysis by more than 180% in all but one patient. The neonates' mean umbilical artery pH was 7.32 (7.27 to 7.41), the mean five minute Apgar score was 10 (8 to 10). PMID- 1936864 TI - [Receptivity of the endometrium: comparison of ultrasound and histologic findings after hormonal stimulation]. AB - On the day of the scheduled embryo transfer, endometrial biopsies were taken from 53 patients of an IVF-programme. There was subsequent failure of fertilisation in all of these patients. The histologic pattern, compared with reflectivity and thickness of the endometrium was determined sonographically on the same day. All patients had been stimulated with hMG/hCG, and the ovaries and the endometrium had been monitored by transvaginal sonography. The reflectivity pattern was divided into grades (A to D according to Smith et al., 1984) and related to histological findings. The distribution of the grades was as follows: 16 patients (30%) grade A, 22 patients (42%) grade B, and 15 patients (28%) grade C. There was no case of grade D in our study. The results of histologic examination for grades A to C were not significantly different from each other. However, in only 37% of grade A, 63% of grade B and 66% of grade C, the endometrial response corresponded to the state of the cycle. Endometrial thickness for the receptive and non-receptive groups was not significantly different (8.8 +/- 0.29 mm vs. 9.13 +/- 0.4 mm). The results show no correlation between histologic findings and endometrial thickness or reflectivity. We therefore conclude, that sonographic determination of these parameters is not helpful in the evaluation of the degree of endometrial response. PMID- 1936865 TI - [Primary urethral cancer in the female: a diagnostic and therapeutic challenge]. AB - Primary carcinoma of the urethra in women is extremely rare and associated with non-specific symptoms of the lower urinary tract, the vagina and the pelvic floor. On the basis of four case reports, the frequent delay in diagnosis is presented and the therapeutic course is outlined. PMID- 1936866 TI - [Morphologic and functional long-term results after Vecchietti operation for the formation of a neovagina]. AB - For creation of a neovagina in patients with congenital vaginal agenesis, a variety of operative procedures are recommended. Basically, two different procedures are described: (1) Application of pressure or traction to the perineum and (2) plastic-surgical operations. Since 1981, the 2nd Department of Obstetrics and Gynecology, Vienna, utilises the method described by Vecchietti. 9 Patients with congenital absence of the vagina and one with vaginal occlusion after radiotherapy underwent Vecchietti's procedure. Patients were seen after a follow up period of at least 5 years. We evaluated morphological and functional long term results using a detailed questionnaire as well as clinical investigations including cytological smears, screening for vaginal infections and determination of sexual hormone levels in peripheral blood. To evaluate distensibility and greatest cross-sectional diameter of the neovagina, a vaginal cast (vinyl polysiloxan) was obtained. All patients treated for congenital malformations showed good to excellent functional results. PMID- 1936867 TI - [Familial hydatidiform mole syndrome and genetic aspects of this disturbed trophoblast development]. AB - A female sibship is presented, where in a total of six sisters aged 16 to 34 years three women suffered from recurrent hydatiform molar pregnancies. Until now none of them has given birth to a child. The family's pedigree and the seven molar events are shown, and cytogenetic findings of complete and incomplete (partial) hydatiform mole as described in the literature and with regard to histomorphological changes. Finally, "genomic imprinting" means that it makes a difference whether chromosomes are derived maternally or paternally (parental origin effect). PMID- 1936868 TI - [Cerebral metastasis of breast cancer--follow-up and therapeutic procedure]. PMID- 1936869 TI - [Circadian and ultradian rhythms in gonadotropin secretion: regulation by ovarian steroids]. AB - By virtue of the close temporal and functional coupling between intermittent hypothalamic GnRH stimulation and hypophyseal gonadotropin response, assessment of the serum gonadotropin pulsatility and its circadian variations may represent a feasible approach to accurately assess neuroendocrine regulation processes in human reproduction. In the absence of considerable ovarian steroid feedback, as in postmenopausal women, the LH pulsatility with maximal pulse frequencies and amplitudes constitutes an unrestrained basic pulse rhythm. During the menstrual cycle, the pulse characteristics of episodic LH secretion and their circadian excursions undergo characteristic alterations by the changing sex steroid environment. Yet, even during cycle phases of increased oestrogen and progesterone concentrations, the LH pulse frequency is limited to that of the basal rhythm. The LH secretory amplitudes increase from the follicular to the luteal phase, presumably as reflection of an altered pituitary sensitivity to endogenous GnRH stimulation. The tight coupling between the LH signal and the sex steroid response from the corpus luteum emphasizes the importance of central stimulatory rhythms for the target organ. The activity of the central "pulse generator" is profoundly modulated by ovarian steroid feedback and by interactions within the neuroendocrine regulatory units. These regulatory processes have been integrated in a hypothetic model of hypothalamic-pituitary interactions, presumably representing the biochemical basis for the regulation of the central pacemaker. PMID- 1936870 TI - [Use of methadone in obstetric and gynecologic management of drug-dependent females with and without HIV infection]. AB - In the course of obstetrical and gynecological care, 113 women with acute intravenous drug use (IVD) participated in a methadon detoxification. In addition to medical treatment, socio-paedagogical intervention was part of the approach. A total of 212 cycles of methadon detoxification have been administered since patients' relapse during or after detoxication had a chance of readmission. In 45% of the attempts, detoxification could be fully achieved. An investigation of actual drug behaviour of the participating women in October 1990 showed, that 23.9% had abstained from drug consumption for at least 6 months ("drug free"). According to the HIV status and pregnancy 4 groups with comparable age (mean 27.7 years) and duration of drug dependency (mean 7.5 years) were classified. There were remarkable differences in drug behaviour between these groups. Of the HIV infected women treated during pregnancy, 36% were drug free. Of the HIV-infected women without pregnancy and pregnant women without HIV-infection, comparable proportions (approx. 27% each) were living without drugs. All but one HIV negative women of the group without pregnancy (3.8%) consumed drugs. In conclusion, pregnancy and subsequent motherhood seems to enhance and stabilize the motivation to quit drug consumption. The significant difference between the HIV-negative and HIV-positive women without pregnancy suggests, that besides pregnancy, the awareness of HIV-infection and of a limited life expectancy has also a positive influence on drug behaviour. PMID- 1936871 TI - [Clinical significance of the classification of hypertensive diseases in pregnancy]. AB - In a prospective study we found a hypertonic disease in 5.26% of the pregnant women. The course of pregnancy and delivery in women with chronic hypertension (22.1%) and in women with a pregnancy hypertension (53.3%) was without complications; delivery of eutrophic children was on term. Pregnant women with pre-eclampsia (19.7%) had an early birth of dystrophic, retarded children (below the 10th percentile). The acidosis morbidity (36.4%) and the frequency of Caesarean section (79.2%) were significantly increased compared to other hypertension types. More often we found pathological para-clinical changes. The perinatal mortality occurred in women with pre-eclampsia in 10.4%. It was not increased in all other hypertension types. The emphasis in prepartal monitoring should be on women suffering from pre-eclampsia. PMID- 1936872 TI - [Comments on pH-metry in umbilical cord blood]. AB - We report on a case of a premature newborn, delivered at 33rd week of gestation, weighting 1650 grammes, which had extremely low actual pH-values (UA: pH = 6,697; UV: pH = 6,803) but surprisingly good Apgar scores (8-10-10). During the following 6 weeks, the newborn did not present any neurological or other abnormalities. Against the background of this case report, all important variables of the fetal acid-base balance in the blood of the umbilical artery and vein are evaluated (Obstetrical data-base of the Department of Obstetrics and Gynaecology of the University of Tubingen, Prof. Dr. H.A. Hirsch). The study population included 2549 vaginal deliveries of singletons, born at term, without any malformations and without premature rupture of the membranes. In 1% of these newborn, the actual pH values in the blood of the umbilical artery were below 7.100 and 16% below 7.200. Computational analysis shows that in these foetuses, 86% of the foetal acidotic load, which must be eliminated by the mother, is due to foetal CO2 production, whereas only 14% is due to metabolic processes. Therefore, the distribution of actual foetal pH-values can be widely influenced by maternal breathing habits during the third stage of labour. We hypothesize that the wide range of pH-value distribution in different obstetrical departments might be due to a different management of the second stage of labour (duration and quality of bearing-down efforts, control of breathing, anaesthesia...). We conclude therefore, that even extremely low actual pH-values in umbilical blood do not necessarily relate to brain damage. PMID- 1936873 TI - [Significance of surgically corrected heart valve diseases on fertility]. AB - We report on 111 patients, who were operated for heart valve failure. The influence of the operation on fertility was examined. Only 24 women became pregnant. From 34 pregnancies, 4 resulted in early abortion; in 12 cases abortion was performed (8 times for medical reasons), therefore 18 children were born. The remaining 87 operated patients (78.4%) never became pregnant, although only 29 patients were advised against pregnancy. 27 patients decided on various contraceptive methods by themselves. PMID- 1936874 TI - [Value of the tumor markers CA 125, Ca 19-9, CA 15-3 and CEA in endometriosis]. AB - CA 125, CA 19-9, CA 15-3 and CEA were measured in 42 patients with histologically verified endometriosis, who had been treated for six months by the LHRH-analogue buserelin (900 mcg/d intranasally). Before therapy, for all of the markers tested the sensitivity was as follows: CA 125 49%, CA 19-9 19%, CA 15-3 19% and CEA 0%. Pretherapeutically the correlation coefficient between CA 125 and the AFS stages was r = 0.40, indicating no significant relation. Following therapy the correlation between the tested glycoproteins and the AFS stages was less indicative. Only CA 125 showed a significant decrease during treatment (p less than 0.05), which paralleled the therapeutic hypo-oestrogenism. According to our results measurement of CA 125, CA 19-9, CA 15-3 and CEA is not sufficient to replace surgical procedures of monitoring endometriosis. The significant reduction of CA 125 apparently represents loss of ovarian function rather than regression of the disease. PMID- 1936875 TI - [Diagnosis of early extrauterine pregnancy by serum and Douglas pouch fluid hCG level]. AB - In 44 patients with assumed ectopic pregnancy culdocentesis were carried out under transvaginosonographic control. In 23 cases, the clinical diagnosis ectopic pregnancy and in 16 cases, an early intact intrauterine pregnancy could be verified. Five patients had an early abortion. In all patients with an intact intrauterine pregnancy, the cul-de-sac liquid was serious. In 16 of the 23 cases of ectopic pregnancies, the fluid was bloody, 6 aspirates were bloody/serous and one serous. The findings in patients with an early abortion were as follows: three serous, one bloody/serous, one bloody. Further information could be gathered from the comparison of hCG-levels in simultaneously obtained serum samples and cul-de-sac liquid. All intact intrauterine pregnancies were associated with lower hCG-levels in the cul-de-sac liquid than in the serum (ratio: serum/cul-de-sac liquid greater than 1.3). In all ectopic pregnancies but one, we found an inverse constellation (ratio: serum/cul-de-sac liquid less than 0.7). In the described exceptional case the ratio was nearly 1 and when culdocentesis was repeated 5 days later, a ratio of 0.17 proved the clinically suspected ectopic pregnancy. In 3 cases of histologically confirmed intrauterine abortions, the hCG-level in the cul-de-sac liquid was lower than in the serum, in 2 cases of early abortions without histologically proved localisation the hCG level was slightly above the level in the serum. PMID- 1936876 TI - [Marfan syndrome and pregnancy, complicated by dissecting aneurysm]. AB - Pregnant women with a Marfan syndrome carry a risk of developing an aortic arc dissection. As the developing aneurism may be diagnosed by echocardiography, this method should be applied repeatedly during pregnancy. We report the case of a Marfan patient, who developed an acute aortic dissection during the third trimester of her pregnancy and discuss the guidance and surveillance of Marfan patients who are or wish to become pregnant. PMID- 1936877 TI - [Transitory osteoporosis in pregnancy; diagnosis with MRI. Case report]. AB - A case of transitory osteoporosis of the hips in pregnancy is reported. Through knowledge of the typical course of the disease and exact diagnosis with MRI, expensive therapy can be avoided. Suspicion of a transitory osteoporosis in pregnancy is a clear indication for performing an MRI. PMID- 1936879 TI - [Goldblatt phenomenon of the uterus and latent kidney disease as a cause of pregnancy-induced hypertension]. PMID- 1936878 TI - [Origin of the urge to press in the expulsion period]. AB - So far, the explanation of the bearing-down pains in the expulsion phase has been unsatisfactory. It is assumed that the press reflex is caused by the pressure of the presenting part on the pelvic floor. This is in contradiction to the observation that the press reflex only appears during labour pains and may occur before the presenting part reaches the pelvic floor. In the expulsion phase, the uterine contraction tenses the ligg. cardinaliae, the vagina and the rectal wall in neighbourhood of the vagina. The tension of the rectal wall leads to an urgent need of relieving bowels, which supports the press reflex. By pressing, the woman perceives a pain relief because of a reducement of the tension of the ligg. cardinalia. PMID- 1936881 TI - [Roentgenologic endovascular occlusion of the spleen in the treatment of hereditary spherocytic hemolytic anemia in children]. AB - Roentgenoendovascular occlusion of the spleen has been suggested for the treatment of children with hereditary spherocytic hemolytic anemia as an alternative to splenectomy. The operation was conducted in 8 children aged from 1 to 11 years. Selective decontamination of the intestine was used for prevention of inflammatory complications. Occlusion of 60% of the splenic parenchyma results in a stable clinico-hematological effect and can be performed as a single stage. Young children could be operated on by this method. PMID- 1936880 TI - [Antioxidant activity of blood serum amd erythrocytes in patients with refractory anemia]. AB - Iron metabolism was studied in patients with refractory anemia. It is shown that continuous transfusions of erythrocytes result in a sharp rise of iron reserves that plays an important role in the development of hemosiderosis. To prevent iron oxidative action it is recommended that the patients should be subjected to therapy with chelating agents and antioxidants simultaneously with transfusions of erythrocytes. A relationship has been noted between blood antioxidant capacity decrease and iron-overloading. PMID- 1936882 TI - [Diagnosis of HIV-induced infection in the USSR using the immunoenzyme methods]. PMID- 1936884 TI - [Sickle cell anemia]. PMID- 1936883 TI - [Results of hematological examinations of crew members of the space vehicles EO 2, EO-3 and EO-4]. AB - The authors' opinion that adaptation inhibition of erythron functioning under weightlessness produces an unfavourable effect on the optimal physical state of a cosmonaut and his working capacity in the post-flight period has been confirmed by the analysis of certain hematological parameters studied in cosmonauts. The data obtained have necessitated investigation of threshold values of erythron functioning under weightlessness, and creation of artificial gravitation on board the piloted space ship to normalize erythropoiesis. Investigation of these problems of space hematology would be helpful in validation of the limits of human's long-term stay under weightlessness, and in the pre- and post-flight period management. PMID- 1936885 TI - [Regulation of erythropoiesis in patients with iron deficiency anemia]. AB - Erythropoietin level in the blood plasma, iron metabolism, and some erythron parameters characterizing anemia expression, erythropoiesis effectiveness and processes of hemoglobin synthesis were studied in patients with iron-deficiency anemia (IDA). The results of the investigation helped the authors to establish that hormone production in IDA patients is under the control of a feedback mechanism that is functioning at a lower level as compared to other non-renal anemias. It has been suggested that optimum possible erythron functioning in IDA patients is achieved under these conditions. PMID- 1936886 TI - [Changes in protein conformation and lipid levels in the erythrocyte membrane after exposure to surface-active agents]. PMID- 1936887 TI - [Immunophenotype of thymocytes and the synthesis of interleukin-2 by the thymus gland cells in children during the 1st year of life]. PMID- 1936888 TI - [A method of studying the hypertonic resistance of erythrocytes]. PMID- 1936889 TI - [Diamond-Blackfan anemia: pathogenesis, clinical aspects and treatment]. PMID- 1936890 TI - Effect of gossypol on kinetics of mouse liver alcohol and aldehyde dehydrogenase. AB - 1. Gossypol, an antifertility ingredient of the cotton plant, altered specific activity of mouse liver alcohol dehydrogenase (L-ADH) and subcellular aldehyde dehydrogenase (L-ALDH) in mice of both sexes. 2. Intraperitoneal injection of a single gossypol dose, 50 mg/kg, inhibited both male and female L-ADH and cytoplasmic L-ALDH from saline controls 21 hr after drug treatment. 3. Gossypol inhibited female but not male mouse mitochondrial L-ALDH isoenzymes. 4. Gossypol produced enzyme inhibition was determined as noncompetitive. 5. The results suggest gender-dependent sensitivity of mitochondrial L-ALDH to the gossypol inhibition. A toxic metabolic interaction between ethanol and gossypol has been indicated which suggests the contraindication of alcoholic beverages during gossypol use. PMID- 1936891 TI - Interaction between morphine and noradrenaline on isolated heart muscle. AB - 1. We evaluated the interaction between morphine and noradrenaline on the right atria. 2. Noradrenaline significantly increased atrial contraction rate, with an effective concentration 16 (EC16) of 85 +/- 0.8 x 10(-9) M. 3. The EC16 of noradrenaline significantly decreased in the presence of morphine. 4. These results demonstrate that morphine increases the potency of noradrenaline on the isolated right atria. PMID- 1936892 TI - Effects of bepridil, diltiazem and verapamil on atrial refractoriness and heart rate in the conscious dog: comparison with quinidine. AB - 1. Bepridil at cumulative doses between 1.25 and 8.75 mg/kg and quinidine between 2.5 and 17.5 mg/kg given in conscious dogs with chronic atrioventricular block and implanted atrial pacing electrodes, dose-relatedly lengthened atrial effective refractory period (AERP), as reflected by the decrease in maximal atrial frequency determined by pacing. 2. Diltiazem shortened AERP at 0.25 mg/kg and lengthened it at 1.75 mg/kg, but both effects were very slight. 3. Verapamil between 0.06 and 0.435 mg/kg did not alter AERP at all. 4. Except for diltiazem at 0.75 and 1.75 mg/kg and bepridil at 8.75 mg/kg, each dose of each drug increased atrial rate. Each drug produced an increase in ventricular rate and a short-lasting lowering in mean blood pressure. 5. Thus, these results indicate that bepridil exhibits more marked antiarrhythmic potentialities than quinidine and that the atrial and ventricular tachycardic effects observed are mainly baroreceptor reflex effects. PMID- 1936893 TI - Calcium antagonists inhibit contractions to norepinephrine in the rat aorta, in the absence, but not in the presence of the endothelium. AB - 1. To compare the effect of diltiazem and verapamil on the responsiveness of vascular smooth muscle to norepinephrine in the presence and absence of the endothelium, rings of rat aorta were studied in organ chambers. 2. The removal of the endothelium decreased the ED50 to norepinephrine and augmented the maximal response to the catecholamine. 3. The contraction to norepinephrine consisted of a rapid initial (phasic) and a (tonic) part. The tonic part was reduced in the presence of the endothelium. 4. Diltiazem shifted the concentration-response curve to norepinephrine to the right only in rings without endothelium and reduced the difference in maximal response between rings with and without endothelium. 5. Verapamil abolished the difference in sensitivity (ED50) between rings with and without endothelium. 6. Oxyhemoglobin prevented the inhibitory effect of the endothelium on the response to norepinephrine, and unmasked a shift of the ED50 to the catecholamine to the right by diltiazem in rings with endothelium. 7. These experiments suggest that spontaneously released endothelium derived relaxing factor(s) is a functional antagonist of norepinephrine-induced contractions, presumably by reducing the stimulated influx of extracellular Ca2+. PMID- 1936894 TI - Evaluation of the effect of aldose reductase inhibition on increased basement membrane collagen fluorescence in diabetic rats. AB - 1. It has been proposed that increased fructose contributes to the formation of fluorescent pigments in diabetic tissues. 2. Since the aldose reductase inhibitor sorbinil lowers glomerular fructose concentrations, we examined the effect of sorbinil on the formation of advanced glycation end products in glomerular basement membrane of streptozotocin diabetic rats. 3. Treatment with sorbinil for 30 days after induction of diabetes did not influence the increased fluorescence observed in collagen from glomerular basement membrane of untreated diabetic rats. 4. The results suggest that nonenzymatic glycation by fructose is not a major contributor to the formation of fluorescent advanced glycation end products in basement membrane in experimental diabetes. PMID- 1936896 TI - Adenosine analogs attenuate tolerance-dependence on alprazolam. AB - 1. Tolerance to and physical dependence on alprazolam were induced in mice by administering two doses of a slow release preparation. 2. Physical dependence was evaluated by the abstinence syndrome induced by flumazenil. Tolerance was studied by measuring the motor incoordination induced by a test dose of alprazolam. 3. The intensity of tolerance was decreased by the administration of L phenylisopropyl adenosine (L-PIA), cyclopentyl adenosine (CPA), cyclohexyl adenosine (CHA), N-ethylcarboxamide adenosine (NECA), 8-phenyltheophylline (8 PTP) and theophylline (TP). 4. The intensity of the abstinence syndrome induced by flumazenil was attenuated by L-PIA, CPA NECA, TP and 8-PTP. 5. The results suggest that benzodiazepines may exert, at least in part, their effects by involving adenosine in the central nervous system. PMID- 1936895 TI - Alpha-glucosidase inhibition prevents increased collagen fluorescence in experimental diabetes. AB - 1. The effect of the alpha-glucosidase inhibitor Acarbose on collagen fluorescence reflecting formation of advanced glycation end products was examined in streptozotocin-diabetic rats. 2. Treatment with Acarbose for eight weeks after induction of diabetes prevented the increased fluorescence in skin and tail tendon collagen associated with untreated diabetes. 3. Acarbose improves integrated glycemic control and beneficially influences the consequences of excess glycation in long-lived connective tissue proteins. PMID- 1936897 TI - Effect of progesterone on norepinephrine release from mouse adrenergic terminals in vitro. AB - 1. The in vitro effect of progesterone on norepinephrine (NE) release and contractile activity was analyzed in uterine horns from estrogen-primed and progesterone-primed mice. 2. Progesterone (6-10 nmol/ml) evoked the release of [3H]NE above basal levels from uterine horns in both experimental conditions, the effect of progesterone on estrogen-primed being more important than on progesterone-primed mice uterus. 3. Progesterone also increased electrically evoked [3H]NE release in estrogen-primed uterine tissue, nevertheless no effect was observed in progesterone-primed ones. 4. Progesterone (0.6-10 nmol/ml) inhibited uterine horn isometric contractions only in estradiol-primed mice. This effect was partially blocked in uterine horns from reserpine-treated mice and when propanolol (1 microM) was added to the preparation of estradiol-primed mice uterus. PMID- 1936898 TI - Regional histaminergic potencies in rabbit systemic circulation. AB - 1. Regional activity of histamine was studied in various rabbit arteries, including segments of the aorta, aortic branches, branchout regions and arteries to fore and hind limbs by dose-response experiments. 2. Local histaminergic potencies were found to be heterogenceous. Circular and longitudinal smooth muscle responsivity in the aorta increased in the distal direction; aortic branches have their own histaminergic response characteristics beginning from their branchouts. Paired arteries (right and left subclavia, renal and iliac) possess matching histaminergic activities. 3. The observed characteristics of the responses suggest predetermined distribution of histaminergic activities along systemic circulation which may be regulatory in the distribution of blood. PMID- 1936899 TI - Chronic administration of nicotine fails to alter the MPTP-induced neurotoxicity in mice. AB - 1. The effects of chronic (14 day) administration of nicotine on 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) (15 mg/kg, s.c.)-induced neurotoxicity in C57BL/6 mice were examined. 2. Nicotine pretreatment failed to alter the deficit in locomotor activity and the reduction in striatal levels of dopamine produced by MPTP. 3. Our results do not support a therapeutic action of nicotine in a Parkinsonian animal model. PMID- 1936901 TI - Expression of arylhydrocarbon hydroxylase, epoxide hydrolases, glutathione S transferase and UDP-glucuronosyltransferases in H5-6 hepatoma cells. AB - 1. The presence of arylhydrocarbon hydroxylase (cytochrome P-450 IA1 dependent), glutathione S-transferase, two distinct forms of epoxide hydrolases and UDP glucuronosyltransferases was detected in H5-6 hepatoma cell homogenates using model substrates, selective inhibitors and specific antibodies. 2. The activity of arylhydrocarbon hydroxylase decreased strongly at the first days after plating and remained at a minimal value (1.5 pmol/min per mg) after 5 days of culture. 3. The hydratation of trans-stilbene oxide catalyzed by the soluble form of epoxide hydrolase was very low (11.0 pmol/min per mg), whereas the hepatoma cells contained appreciable amounts of the membrane-bound epoxide hydrolase and glutathione S-transferase measured with cis-stilbene oxide as substrate (maximal specific activity: 1.46 and 2.73 nmol/min per mg, respectively). 4. These cells also glucuronidated 1-naphthol efficiently (6 nmol/min per mg) and, at a lower extent, bilirubin (12 pmol/min per mg). 5. Addition of fenofibrate (70 microM) into the culture medium for 1-3 days failed to significantly stimulate the activity of cytosolic epoxide hydrolase. Only bilirubin glucuronidation increased 2-fold after 2 days of presence of the drug. PMID- 1936900 TI - Rat heart anaphylaxis: influence of mediator antagonists. AB - 1. Parameters of isolated hearts from rats which were actively sensitized to ovalbumin were found to be impaired on ovalbumin challenge: the heart rate increased whereas the contractility force and coronary flow decreased significantly. 2. Treatment in vivo or in vitro with histamine receptor antagonists (promethacine and cimetidine), the leukotriene antagonist FPL 55712, the PAF antagonist BN 52021, the combined prostaglandin endoperoxide receptor antagonist/thromboxane A2 synthesis inhibitor R 68070, the thromboxane synthetase inhibitor HOE 944, the lipoxygenase inhibitor ZIMET 47/79, the antioxidant sodium hyposulfite or with dexamethasone caused a different improvement of the parameters to a different degree. 3. Consequently, histamine, leukotrienes, PAF, activated oxygen, thomboxane A2 and possibly further autacoids might be involved in mediating the described anaphylactic reaction. PMID- 1936902 TI - Effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanol amines on the spontaneous and evoked contractions in the rat isolated uterus. AB - 1. The effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanol amine (compounds M & E), respectively and diltiazem (D) were examined on the spontaneous and evoked uterine contractions of pregnant rats in vitro. 2. Addition of compound M (75-300 microM), compound E (15-60 microM) or D (100-400 nM) to the uterine tissues, inhibited the spontaneous contractions in a dose-dependent manner. The potency order was D greater than E greater than M. 3. The inhibitions were reversed by elevating the extracellular Ca2+ concentration by 20 mM. The compounds also antagonised CaCl2-evoked contractions. 4. Treatment of rats with either compound during pregnancy days (1-16) did not affect the implantation process and did not induce any teratogenicity. 5. The uterine inhibitory effects of the compounds may be due to blockade of uterine Ca2+ channels. PMID- 1936903 TI - Propylbenzilylcholine mustard-sensitive and -resistant muscarinic receptors in cardiac muscle. AB - 1. A left atrium of guinea pig driven electrically was used as a test organ containing M2-cholinoceptors. 2. Concentration-response curves of carbachol and butyltrimethylammonium, muscarinic full agonists, were progressively inhibited by 10 and 30 min treatments of the atrium with propylbenzilylcholine mustard (PrBCM; 10(-6) M). The 50 min treatment with PrBCM had no further significant inhibitory effect on their curves. 3. The 30 min treatment of the atrium with PrBCM completely inhibited the concentration-response curve of pilocarpine, a partial agonist. In the atrium after the 30 min treatment with PrBCM, pilocarpine shifted the concentration-response curves of the full agonists, suggesting a competitive antagonism. 4. These results suggest an existence of two subtypes of M2 receptors; PrBCM-sensitive and -resistant ones, and that the full agonists inhibit the twitch through an interaction of both the receptors, while the partial agonist produce inhibition through an activation of PrBCM-sensitive ones. PMID- 1936904 TI - Impact of neonatal benzpyrene imprinting on thymocytic dexamethasone binding in ascitic tumor bearing rats. AB - 1. Rats treated with a single dose of benzpyrene when newborn and inoculated with Walker's ascitic tumor cells when 6 weeks old showed 6 and 9 days later an unequivocal increase, whereas 15 and 20 days later an unequivocal decrease, in dexamethasone binding capacity (receptor number) relative to the control, i.e. a reversion of receptor activity in the course of tumor genesis. 2. The reversion of receptor activity showed a parallelism with the increase of tumor mortality over the control. 3. The experimental observations support the conclusion that neonatal exposure to benzpyrene has a depressive effect on general resistance that is reflected (or probably caused?) among others by a decrease in the binding capacity of glucocorticoid receptors. PMID- 1936905 TI - Effects of vanadate, ouabain and amiloride on the contraction of the rat testicular capsule to oxytocin. AB - 1. The modification of the contraction of the rat testicular capsule to oxytocin (OT) by vanadate (0.7, 7 and 70 microM), ouabain (0.1 mM), and amiloride (10 microM to 1 mM) have been studied. 2. OT (1 nM-6 microM) and vanadate (10 microM 3 mM) induced contraction of the rat testicular capsule in a dose-dependent way (ED50: 188 +/- 66 nM and 82.8 +/- 7.4 microM, respectively). 3. Vanadate (0.7, 7 and 70 microM) and ouabain (0.1 mM) increases the contractile effect of OT (50 and 200 nM). 4. Amiloride (10 microM-1 mM) inhibit, in a dose-dependent way, the OT-contraction. 5. Amiloride (10 microM or 50 microM) block the ouabain but not the vanadate potentiation to OT. PMID- 1936906 TI - Influences of sodium on the contraction induced by oxytocin in rat testicular capsule. AB - 1. The effect of tetrodotoxin (5 microM), monensin (10 microM) and the replacement of Na+ by choline (choline medium) on the contractions of the rat testicular capsule induced by oxytocin (50 and 200 nM) have been studied. 2. The sodium channel blocker tetrodotoxin did not modify the oxytocin contraction. 3. The sodium ionophore monensin produces contraction of rat testicular capsule and reduces the oxytocin-induced contraction. The monensin contraction is inhibited by amiloride (0.1 mM). 4. Replacement of Na+ by choline increases the contraction induced by oxytocin and KCl (60 mM) but inhibits that induced by noradrenaline (3 microM). 5. The increase of contraction due to oxytocin in choline medium is inhibited by amiloride (50 microM and 1 mM) and when calcium is suppressed of the incubation medium. PMID- 1936907 TI - Influence of psychogenetics in opiate tolerance and abstinence in mice. AB - 1. Four different strains of mice were used to study the influence of psychogenetics in opiate tolerance and abstinence. 2. The CD1 strain seemed to be more sensitive to naloxone administration after four days of morphine implantation, because administration of the antagonist induces a number of jumps in the withdrawal phase higher than in the case of the DBA or C3H strains. 3. DBA and C3H mice elicit analgesia before the CD1 strain, whereas the C3H mice lose body weight at a faster rate than the other strains. 4. C57 bl mice died after morphine implantation (100%). 5. These findings are discussed in relation with neurochemical and receptor variations. PMID- 1936908 TI - Factors in the lethality of i.v. phencyclidine in conscious dogs. AB - 1. Pretreatment were pancuronium prevented convulsions and hyperthermia, but had no effect on acidemia or changes in cardiovascular parameters after intravenous (i.v.) infusion of phencyclidine (PCP). 2. While dogs survived higher amounts of PCP, they failed to regain spontaneous respiratory function. 3. Mechanical ventilation alone increased the mean lethal dose/time of PCP and reduced the effects of PCP on arterial systolic pressure, cardiac output, and PCO2. 4. EKG showed ventricular arrhythmias, which progressed to death. 5. Phenytoin pretreatment plus respiratory assistance increased the lethal dose and reduced PCP effects on cardiovascular parameters, body temperature, and cardiac rhythm. 6. Blocking of convulsions prevented hyperthermia and acidemia; respiratory support reduced circulatory effects, but respired dogs then died, at higher doses, from a primary myocardial toxicity of PCP. PMID- 1936909 TI - Effects of forced shaking stress at low temperature on pentobarbital-induced sleeping in mice. AB - 1. Effects of a new stressful manipulation, forced shaking stress at low temperature (4 degrees C) (FSLT stress), on sleeping induced by pentobarbital were investigated 70 min following its application. 2. Repeated application (7 times) decreased the duration of sleep induced by pentobarbital-Na (45 mg/kg, i.p.) in mice without affecting that induced by ketamine-HCl and chloral hydrate. This effect of FSLT stress disappeared 3 days after termination of application. 3. The latency of nociceptive response in hot-plate test increased in a naloxone sensitive manner by single and repeated FSLT stress when tested immediately (2 min) after but not 70 min after the last stress application. 4. Diazepam (0.3 mg/kg, i.p.) significantly prolonged the duration of sleep induced by pentobarbital (45 mg/kg, i.p.) in stressed animals without changing that in unstressed animals. The effect of diazepam was blocked by Ro 15-1788 (10 mg/kg, i.p.), a specific benzodiazepine receptor antagonist. 5. Repeated FSLT stress thus appears to decrease pentobarbital sleep by inducing functional changes in the central nervous system and the GABAergic system may partially participate in FSLT stress-induced decrease in pentobarbital sleep. PMID- 1936910 TI - Capric acid as a potent dilator of canine vessels in vitro and in vivo. AB - 1. Pharmacodynamic effects of even numbered saturated fatty acids, C4-C16, were determined on isolated canine basilar and femoral arteries precontracted with PGF2 alpha. 2. The fatty acids relaxed the precontracted vessels. 3. The basilar artery was the most sensitive vessel and caprate (C10) was the most potent acid with an EC50 of 49 microM. 4. The relaxant effect was endothelium-independent. 5. Contractions elicited by norepinephrine, serotonin, and U46619 were also inhibited. 6. Caprate (C10) given intra-arterially increased femoral blood flow in a dose-dependent manner and the dose computed to increase blood flow 50% was 1.27 microM/kg. PMID- 1936911 TI - Colchicine inhibition of duodenal absorption of calcium. AB - 1. The effect of colchicine on calcium absorption across rat duodenum has been investigated using the single-pass continuous perfusion technique and the two compartment system model. 2. Perfusing the rat duodenum with 0.1 and 0.5 mM colchicine produced a dose-dependent inhibiting pattern of calcium transport with no effect noted for water transport. 3. Colchicine at 0.5 mM caused a significant decrease in the rate of calcium uptake and in the accumulation capacity of the duodenal cells. 4. Accumulation of calcium in the duodenal strips displayed saturation kinetics with increasing concentration of calcium in the incubation medium. Colchicine at 0.5 mM showed a lower saturation level and decreased the average maximal flux around 46%. PMID- 1936912 TI - Interaction of bradykinin and angiotensin in the regulation of blood pressure in conscious rats. AB - 1. The interaction between bradykinin (BK) and the renin-angiotensin system was studied in conscious, catheterized rats. 2. Intravenous injection of BK induced dose-dependent decreases in blood pressure in normotensive Wistar and Wistar Kyoto rats and spontaneously hypertensive rats. Pretreatment with the angiotensin converting enzyme (ACE) inhibitor captopril markedly enhanced the effect of BK, such that the dose-response curve shifted significantly to the left in all three strains. 3. In a second series of experiments, captopril did not change basal blood pressure, but blocked the pressor response to angiotensin I (AI), but not angiotensin II (AII). 4. The partial agonist Sar1-Ala8-angiotensin II (SAR) increased blood pressure and blocked the pressor response to subsequent AII treatment. 5. After pretreatment with BK (50 micrograms/kg), captopril evoked a decrease in blood pressure, while still blocking the effect of AI. 6. After pretreatment with BK, SAR decreased blood pressure, while still antagonizing the action of AII. 7. These results suggest that ACE plays a role in the inactivation of circulating BK in normotensive and hypertensive rats. Conversely, BK can influence the activity of the renin-angiotensin system, probably by interacting with ACE. PMID- 1936913 TI - Changes in arginine vasotocin content in the pituitary of the Medaka (Oryzias latipes) during osmotic stress. AB - Changes in the arginine vasotocin (AVT) neurons of the medaka, Oryzias latipes, during osmotic stress were studied by means of immunohistochemistry and radioimmunoassay. AVT neurons were identified by their immunoreactivity to anti arginine vasopressin serum, which crossreacts with AVT. When freshwater (FW) adapted fish were transferred to seawater (SW), the number of immunoreactive magnocellular neurons decreased, while the cell nuclear size increased. AVT content in the pituitary significantly decreased 2 hr or 1 day after transfer to SW, but returned to approximately the initial level 1 week after transfer. However, when SW-adapted fish were transferred to FW, the number of immunoreactive magnocellular neurons increased from 1 hr after readaptation to FW, but the cell nuclear size failed to show significant changes. AVT content in the pituitary significantly increased 1 or 2 hr after transfer. These results seem to indicate that AVT secretion in the medaka was temporarily accelerated by exposure to SW and inhibited immediately after transfer to FW. PMID- 1936914 TI - The control of testicular androgen production in the goldfish: effects of activators of different intracellular signalling pathways. AB - The putative roles of different signal transduction pathways in the regulation of testicular androgen production in goldfish were investigated. In addition to the role of the gonadotropin-adenylate cyclase pathway, which was studied using human chorionic gonadotropin and forskolin, we determined the effects of changes in intracellular calcium content and protein kinase C activation on androgen production using calcium ionophore A23187 and phorbol 12-myristate 13-acetate (PMA), respectively. Testis fragments incubated in vitro respond to hCG in a time and dose-dependent manner with a resultant increase in the secretion of testosterone (T) and 11-ketotestosterone (11-KT). Although ineffective alone, PMA (400 nM) and A23187 (4000 nM) stimulate a small but significant increase (3-fold above basal) in T production. This response is minor compared to the up to 200 fold increase in T secretion observed in response to either hCG or forskolin. PMA (25-400 nM) alone and A23187 (250-4000 nM) alone inhibit the stimulatory actions of hCG on T production. Unlike PMA, the inactive phorbol 4 alpha-phorbol didecanoate, which does not activate PKC, had no effect on hCG-stimulated T production. PMA and A23187 did not influence the effects of forskolin on T production, suggesting that the compounds exert their effects prior to adenylate cyclase activation. In summary, the present studies suggest that in addition to the stimulatory actions of the adenylate cyclase second messenger system, changes in intracellular calcium content and protein kinase C activation may modulate testicular androgen production in the goldfish. PMID- 1936916 TI - Seasonal reproduction in subtropical brahminy myna, Sturnus pagodarum: role of photoperiod. AB - Experiments were performed to study the extent of the involvement of photoperiod in the timing of seasonal reproduction in brahminy myna (Sturnus pagodarum). The reproductive cycle corresponds to annual variations in day length and there is a marked seasonal variation in the photogonadal response of birds, which is evident when birds are shifted from normal day length to long photoperiods (15L:9D) every month. This is supported by the results from constant long (15L:9D) and short (9L:15D) photoperiodic treatments. Whereas the reproductive cycle was abolished in short photoperiods, a 15L:9D photoperiod induced a single complete gonadal growth-involution cycle after which birds became photorefractory. Further, exposure of birds to 8L:16D during different phases of the reproductive cycle indicated that the effect of short photoperiods on advancement of photosensitivity depended on the reproductive status attained when shifting took place. These laboratory investigations clearly suggest that the annual photocycle affects the timing of the reproductive cycle of brahminy myna. PMID- 1936915 TI - Characterization of epidermal growth factor binding to hepatic plasma membranes of rainbow trout (Oncorhynchus mykiss). AB - Epidermal growth factor (EGF) is a potent mitogen which exerts its effects through a transmembrane receptor located on target cells. Since little is known about EGF in nonmammalian animals, experiments were conducted to characterize the EGF receptor in rainbow trout hepatic cell membranes. The binding of mouse EGF with rainbow trout receptors was peptide-specific, saturable, reversible, and of high affinity. Optimal binding was observed at pH 7.2. Both monovalent and divalent cations augmented the specific binding of EGF, by a factor of two- to threefold over control values, but were not needed for binding to occur. Scatchard plot of the saturation data was curvilinear. Analysis of the data by kinetic methods indicated the curvilinear nature of the Scatchard plot was due to multiple receptor sites of differing affinity and not to site-to-site interactions. Rate constants for association (K11) were 9.38 X 10(8) M-1 * min-1 and 2.28 X 10(7) M-1 * min-1 for the high and low affinity sites, respectively. Rate constants for dissociation (K-1) were 2.03 X 10(-3) min-1 and 2.07 X 10(-1) min-1 for high and low affinity sites, respectively. The apparent dissociation constants determined from the rate constants for the high affinity (KD = 2.3 X 10(-11) M) and low affinity (KD = 9.1 X 10(-9) M) were in agreement with constants estimated by equilibrium methods. Maximum binding capacities were 13 fmol EGF bound/mg protein of protein and 270 fmol EGF bound/mg of protein for the high and low affinity receptor sites, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936917 TI - Greater conservation of somatolactin, a presumed pituitary hormone of the growth hormone/prolactin family, than of growth hormone in teleost fish. AB - From pituitary cDNA libraries of Atlantic cod and chum salmon, cDNA clones coding for somatolactin (SL), a presumed pituitary hormone belonging to the growth hormone (GH)/prolactin (PRL) family, were isolated and characterized. The 1.3-kb cod SL mRNA was composed of a greater than 0.25-kb 5' untranslated region, a coding region for the precursor of 235 amino acids (aa), a 0.14-kb 3' untranslated region, and a poly(A) tail. The 2.5-kb salmon SL mRNA had a less than 0.1-kb 5' untranslated region, a precursor (233 aa) coding region, a 1.6-kb 3' untranslated region, and a poly(A) tail. A signal peptide of 26 and 24 aa was found in the SL precursor of cod and salmon, respectively. Thus, the mature SLs of these fish are composed of 209 aa. Two potential N-glycosylation sites were identified in cod SL, whereas no site could be found in the salmon. A comparison of amino acid sequences of the three SLs so far isolated indicated six Cys residues to be in homologous positions to those in GH and PRL, and one Cys residue to be characteristically present in SL. Among cod, salmon, and flounder, greater colinearity of amino acid sequences was noted in SLs than in GHs. The identities of the SL amino acid sequences were between 73 and 81% as compared to 58-62% for the corresponding GHs, indicating greater conservation of SL than GH. PMID- 1936918 TI - Sex-reversal of male Armadillidium vulgare (Isopoda, Malacostraca, Crustacea) following andrectomy and partial gonadectomy. AB - Evidence is presented for the first time for the complete sex-reversal of genetic males of the terrestrial isopod Armadillidium vulgare into functional females following partial gonadectomy. Fifth-instar males were used. The anterior half of their rudimentary reproductive organs along with the attached androgenic glands were removed. Six months later these animals formed oostegites and laid eggs, and when bred with normal males, produced only male offspring. These results show that in the absence of the androgenic gland, female sex characteristics differentiate and oogenesis occurs in genetic males. PMID- 1936919 TI - Increased urotensin I and II immunoreactivity in the urophysis of Gillichthys mirabilis transferred to low salinity water. AB - The function of the fish caudal neurosecretory system is uncertain, but a role in osmoregulation has been suggested by many investigators. Our objective was to determine if acclimation to water of different salinity has an effect on immunoreactive patterns and staining intensities of the two caudal neuropeptides, urotensins I (UI) and II (UII), in Gillichthys mirabilis. Five fish, originally maintained in seawater, were transferred to deionized fresh water (FW), and five were transferred to new seawater (SW). After 24 hr spinal cords were removed and fixed, FW and SW spinal cords were paired in blocks to receive identical treatment, and cryostat sections were double immunostained for both peptides using a double sequential immunofluorescence procedure. FW spinal cord exhibited increased staining intensities for both UI and UII in their urophyses (the neurohemal organ) compared to the SW spinal cords. The magnitude of intensity difference appeared greater for UI than for UII. In addition, the FW urophyses had more loci displaying intense, perivascular UI immunoreactivity than the SW urophyses. Thus, it appears that environmental salinity has an effect on the urophysial content of UI and UII in this euryhaline fish. The increased immunoreactivity in FW fish could reflect increased synthesis and storage, decreased release of the stored peptides, or decreased peptide degradation. PMID- 1936920 TI - Daily infusion of corticosterone and reproductive function in the domestic hen (Gallus domesticus). AB - The purpose of this study was to examine the effect of the daily infusion of corticosterone on reproductive function in the laying hen and to determine the relationship between the cyclic pattern of plasma concentrations of corticosterone on the open-period for the preovulatory release of LH. An exogenous rhythm of plasma levels of corticosterone was generated using an osmotic pump. Corticosterone was infused subcutaneously into laying hens at rates of 5, 10, 15 or 30 micrograms/hr for a duration of 10 hr beginning with the onset of darkness or at 15 micrograms/hr for 4 hr, or continuously at 30 micrograms/hr. Daily infusions greater than 15 micrograms/hr and the continuous infusion resulted in cessation of ovulation, ovarian and oviductal regression, hyperphagia, and elevated levels of plasma corticosterone compared to that observed in control hens. The hens which were infused with 5 or 10 micrograms/hr of corticosterone maintained normal reproductive function with plasma concentrations of corticosterone that were approximately the same as those in the control hens. The effect of infusing 10 micrograms/hr of corticosterone on the open-period for the preovulatory release of LH was determined under constant light. No significant changes were observed in the frequency distribution of the times of oviposition when hens were infused with 10 micrograms/hr of corticosterone for 12 hr from 9:00 to 21:00 hr or 21:00 to 9:00 hr each day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936921 TI - Cells showing immunoreactivity for calcitonin or calcitonin gene-related peptide (CGRP) in the central nervous system of some invertebrates. AB - In the central nervous system of some species of several invertebrate phyla, including land planarians (Platyhelminthes), ribbon worms (Nemertina), slugs (Mollusca), polychaetes, earthworms and leeches (Annelida), pill bugs (Arthropoda), and beard worms (Pogonophora), salmon calcitonin-immunoreactive cells and rat calcitonin gene-related peptide (CGRP)-immunoreactive cells were found by immunohistochemistry. These immunoreactive cells were located in the region surrounding the neuropile, although the sizes of the cells varied according to species. Some of them were round or polygonal and regarded as apolar nerve cells because of their lack of cytoplasmic processes, whereas others were spindle-shaped or elongated, being comparable with unipolar nerve cells because of extension of their cytoplasmic processes in the direction of the neuropile. In some cases, it was noted that the cytoplasmic processes had complicated branches or formed loop-like structures at their ends. These observations suggest that a calcitonin-like or CGRP-like substance is extensively present in invertebrates as well as vertebrates. PMID- 1936922 TI - Identification and preliminary characterization of white sturgeon (Acipenser transmontanus) vitellogenin mRNA. AB - Vitellogenesis was induced in white sturgeon by administration of estrogen through silastic implants. Vitellogenin mRNA was identified by agarose gel electrophoresis and cell-free translation. A highly abundant 5.7-kb mRNA was induced in the liver of estrogen-treated sturgeon. Cell-free translation of poly(A)+ mRNA showed the induction of two high-molecular-weight proteins of 180 and 120 kDa. These two proteins, encoded by the 5.7-kb mRNA(s), were immunoprecipitated by antiserum to serum from vitellogenic sturgeon. Immunoprecipitations also showed the presence of four other serum proteins synthesized by the liver of estrogen-treated sturgeon. The induction of vitellogenesis by estrogen in sturgeon, which are a primitive teleost, was found to be similar to induction of vitellogenesis in amphibians, avians, and other teleosts. Estrogen treatment induced a highly abundant vitellogenin mRNA as well as several mRNAs for other serum proteins. However, the presence of two distinct vitellogenin monomers in the cell-free translation assay was significantly different from the results in other species. PMID- 1936923 TI - Annual changes in plasma levels of LH, and prolactin in free-living female great tits (Parus major). AB - Plasma levels of LH and prolactin were measured in free-living female great tits throughout the year. Plasma concentrations of LH increased at the onset of winter (January), onset of spring (March), nest-building period, (for both the first and the second clutch), last part of the incubation period, (for both the first and the second clutch), and early autumn (August). Plasma prolactin increased between March and April. A further increase occurred during the nest-building period, which continued during the early part of the egg-laying period. Prolactin levels increased further once incubation had started. During nest-building and egg laying of the second clutch, prolactin levels were low, but not basal. Prolactin levels increased again during incubation of the second clutch. Between July and March prolactin levels usually were below the limit of detection of the assay. PMID- 1936924 TI - Prostaglandin-induced secretion of oxytocin and prolactin in red (Cervus elaphus) and Pere David's (Elaphurus davidianus) deer hinds: evidence for oxytocin of luteal origin. AB - Peripheral plasma concentrations of oxytocin in female red deer during the luteal phase of the oestrous cycle (9.3 +/- 2.1 fmol/ml) exceeded those in the follicular phase (3.1 +/- 1.4) or during seasonal anoestrus (3.2 +/- 1.3). In both red and Pere David's deer hinds during the mid-luteal phase of the cycle, systemic administration of a luteolytic dose of the prostaglandin F2 alpha analogue, cloprostenol, caused the concentration of oxytocin in the peripheral circulation to rise. Mean (+/- SEM) concentrations increased from 8.1 +/- 0.7 to 97 +/- 8 fmol/ml in red and from 6.2 +/- 0.7 to 153 +/- 30 fmol/ml in Pere David's hinds within 5 min of treatment. During seasonal anoestrus oxytocin secretion in response to cloprostenol was reduced to less than 10% of that during the breeding season, in both species. Cloprostenol treatment raised circulating concentrations of prolactin in both species during the breeding season, and during anoestrus in red deer only. The concentration of oxytocin in a single corpus luteum removed at laparotomy from one red deer hind at the mid-luteal phase of the cycle was 66 nmol/g wet wt; identification was authenticated by HPLC. These results suggest that the corpus luteum secretes oxytocin in the Cervidae, as established previously in the Bovidae, and that luteal oxytocin secretion is stimulated by prostaglandin. PMID- 1936925 TI - Dissociated effects of tamoxifen on growth and on progesterone receptor induction in quail oviduct. AB - The estrogen agonist and antagonist activities of tamoxifen on growth and progesterone receptor induction were studied in the immature quail oviduct. Tamoxifen alone, when administered for 3 days at doses ranging from 0.01-10 mg/kg, had no effect on oviducal weight, DNA, and protein content, but significantly increased progesterone receptor concentration. When combined with estradiol benzoate (0.1 mg/kg daily for 3 days), tamoxifen completely inhibited the trophic action of estradiol while it only reduced the progesterone receptor concentration in the oviduct by 50%. This latter effect reflected more a reduction in the progesterone-responsive cell population of the tissue rather than a true estrogen antagonist effect on this specific protein induction. These results and previous data from this laboratory support the conclusions that in this model system: (1) the mechanisms involved in the induction of estrogen sensitive cell proliferation and progesterone receptor synthesis are independent, and (2) the estrogen-antagonist activity of tamoxifen on cell proliferation is mediated through an estrogen receptor-independent pathway. Thus, the immature quail oviduct model system is particularly relevant to more detailed studies on the molecular modes of action of synthetic antiestrogens. PMID- 1936927 TI - Effect of the presence of females on plasma testosterone concentration of male marsupial bandicoots, Isoodon macrourus, housed in enclosures. AB - To determine whether the presence of sexually active females influences the reproductive processes of the male bandicoot, plasma testosterone concentrations were monitored in males isolated from females. Blood samples were obtained weekly from 8 male bandicoots housed with females and from 12 male bandicoots in an enclosure without females. Reproductive tracts were obtained from 7 of the male bandicoots of the latter group during the breeding season. In both groups plasma testosterone increased prior to the start of the breeding season and was not influenced by the absence of adult females. There was no significant difference in testosterone concentrations between groups at any time of year. Testicular, epididymal, and prostatic weights of males housed without females were similar to those reported for male bandicoots housed with adult females during the breeding season. These results demonstrate that the seasonal change in reproductive function in the male are not mediated via the female. PMID- 1936926 TI - Estrogenic effect of dietary soya bean meal on vitellogenesis in cultured Siberian sturgeon Acipenser baeri. AB - The unusual presence of vitellogenin in the plasma of male and nonvitellogenic female Siberian sturgeon has been demonstrated previously (Pelissero and Le Menn, 1988; Pelissero et al., 1989a) and was attributed to dietary effects. The present study examines estrogenic effects of dietary soya bean meal and of commercial trout diet on vitellogenesis in sturgeon. The 4-month study compared three diets, one commercial (T) and two experimental synthetic diets, one containing casein alone (SC for synthetic diet made on casein), and the other casein and soya bean (SS for synthetic diet made with soya bean) as protein sources. The dietary soya bean meal contained plant isoflavonic compounds which are well known to mimic the effects of estrogens in mammals. The SC diet, free of estrogenic compounds, served as the reference diet. When fed with the SC diet, sturgeons showed significantly lower plasma vitellogenin levels (0.0045 +/- 0.0012 mg/ml) compared with those fed the commercial diet (1.24 +/- 0.37 mg/ml). The SS diet had a very pronounced effect on the plasma vitellogenin level, which at the end of the experiment had reached 6 mg vitellogenin/ml. In no case was estradiol detectable in the plasma. Plasma androgen levels were high in all the three groups throughout the study period, and not significantly different from one another. Sturgeon fed the T diet had larger livers, with enlarged hepatocytes, compared with those fed the SS and SC diets. PMID- 1936928 TI - Developmental expression of the prolactin gene in the chicken. AB - Steady-state levels of prolactin (PRL) mRNA in the pituitary gland during embryonic development were determined by dot blot analyses to relate the changes with those of pituitary and plasma levels of PRL. Steady-state levels of the 1.38 kb mRNA encoding the PRL prohormone remained low until Day 18 of incubation, increased on Day 19 of incubation, and reached maximum levels on the day of hatch but decreased 1 day after hatch. Changes in both pituitary and plasma concentrations of PRL closely mimicked those changes in PRL mRNA levels. Subsequently, both the levels of the pituitary PRL mRNA and PRL remained unchanged whereas those of plasma PRL increased 7 days after hatch. The results indicate that a progressive expression of PRL gene in the pituitary gland occurs 1-2 days before the hatch and concomitant increases in plasma concentrations of prolactin may be associated with physiologic changes in pulmonary respiration and hatching. PMID- 1936929 TI - The effects of thyroid hormones and starvation on hepatic mitochondrial nucleic acids of rainbow trout (Oncorhynchus mykiss). AB - Twenty four hours after an intraperitoneal injection of thyroxine (T4; 4.4, 44 ng/g body wt) or triiodothyronine (T3; 3.3, 33 ng/g body wt), DNA and RNA were significantly reduced in isolated liver mitochondria of rainbow trout. Total liver DNA was increased with the higher doses in both T4- and T3-injected specimens while total RNA was significantly reduced with the same doses. Total circulating plasma T4 was reduced with the injections of T3 or starvation, and plasma T3 was increased severalfold with the T3 injections. Plasma T4 also increased fivefold after a higher dose of T4 injection while starvation significantly reduced the concentration, when measured by radioimmunoassay. PMID- 1936930 TI - Inositol phosphate formation in uterine tissue from two species of reptiles is stimulated by arginine vasotocin and influenced by stage of reproduction. AB - Phosphoinositide hydrolysis, resulting in inositol trisphosphate (IP3) and diacylglycerol (DG) formation, has been implicated in oxytocin-stimulated pulsatile secretion of prostaglandin F2 alpha (PGF2 alpha) from uterine endometrium of sheep and other mammals. In reptiles, arginine vasotocin (AVT) stimulates uterine secretion of PGF2 alpha. These studies investigated the ability of AVT to stimulate incorporation of [3H]inositol into inositol mono-, bis-, and trisphosphates in two reptilian species. In Experiment 1, AVT stimulated (P less than 0.01) IP formation in uterine from late-gravid (150 to 291%) and postpartum (104 to 363%) Yarrow's spiny lizards (Sceloporus jarrovi). Inositol phosphate formation, in response to AVT, was greater (P less than 0.01 for IP3 and P less than 0.05 for total IP) for gravid (stage 40 embryos) and postpartum (1-2 days) lizards near the time of parturition than for lizards at other stages (stage 38-39 embryos or 7 days postpartum). Inositol phosphate formation was greater (P less than 0.05) in uterine tissue from gravid than from postpartum lizards. In Experiment 2, basal IP formation and the response to AVT were the greatest (P less than 0.01) in endometrium from late-gravid American alligators (Alligator mississippiensis). AVT stimulated (P less than 0.02) IP synthesis in uterine endometrium from vitellogenic (136 to 394%), early-gravid (7 to 270%), late-gravid (315 to 1002%), postpartum (86 to 313%), and nonreproductive (292 to 322%) alligators. Results indicate that (1) AVT stimulates IP formation in the uterus of reptiles; (2) uterine IP formation increases in late-gravid reptiles; and (3) increased responsiveness to AVT may occur at parturition or oviposition. PMID- 1936931 TI - Piromyces rhizinflata nov. sp., a strictly anaerobic fungus from faeces of the Saharian ass: a morphological, metabolic and ultrastructural study. AB - A new species of strictly anaerobic chytridiomycete was isolated from dried faeces of the Saharian ass that had been stored for up to 150 days. Because of its monocentric thallus and uniflagellate zoospores it belongs to the genus Piromyces. It exhibits a high affinity for P. mae and P. dumbonica but differs from them in its morphological and ultrastructural characteristics. Its flagellar apparatus is similar to that of all previously reported fungi. PMID- 1936932 TI - Purification of a GSH-affinity binding protein from Bacteroides fragilis devoid of glutathione transferase activity. AB - An affinity binding protein from the cytosolic fraction of Bacteroides fragilis was purified by using epoxy activated-Sepharose 6B resin immobilized with GSH or with hexyl-GSH. This protein showed a subunit molecular mass (22 kDa) similar to that of glutathione transferase purified from Proteus mirabilis (22.5 kDa). However, the affinity binding protein of Bacteroides fragilis, unlike the GSH affinity binding protein of Proteus mirabilis, was devoid of the capacity to conjugate GSH to the most commonly used glutathione transferase substrates. The GSH-affinity binding protein of Bacteroides fragilis was also antigenically different from the GSH-affinity bound protein of Proteus mirabilis. It was concluded that the anaerobic microorganism is not able to express glutathione transferase even though it contains a GSH-affinity binding protein with a structural characteristic reminiscent of aerobic glutathione transferase. PMID- 1936933 TI - Metabolism of nitric oxide in denitrifying Pseudomonas aeruginosa and nitrate respiring Bacillus cereus. AB - Suspensions of Pseudomonas aeruginosa and Bacillus cereus were continuously sparged with nitrogen to remove gaseous products of nitrate reduction. Under these conditions, P. aeruginosa denitrified nitrate to 4% NO, 47% N2O and 49% N2. B. cereus reduced nitrate to 94% nitrite, 2% NO and 5% N2O. B. cereus was unable to reduce NO or N2O as sole electron acceptor, whereas P. aeruginosa reduced NO stoichiometrically to N2O when the N2O reductase was inhibited by acetylene or when the formed N2O was immediately flushed out of the incubation vessel. The mechanism and the reason for NO production in nitrate-respiring B. cereus are unknown, but the amounts of NO released were in a similar range as in the denitrifying P. aeruginosa and thus may be of similar environmental importance. PMID- 1936934 TI - Construction by polymerase chain reaction and use of intragenic DNA probes for three main types of transferable beta-lactamases (TEM, SHV, CARB) [corrected]. AB - Intragenic DNA probes were synthesized by polymerase chain reaction using fragments of the genes of three major types of beta-lactamases (TEM, SHV, CARB) as templates. The TEM probe hybridized with the genes encoding TEM-1, TEM-2 and six extended-spectrum related enzymes (TEM-3 to TEM-7, TEM-2O) in colony hybridizations and Southern-blot analysis. The SHV probe hybridized with the genes for SHV-1, OHIO-1 and four derived extended-spectrum beta-lactamases (SHV 2, SHV-3, SHV-4 and SHV-5). The CARB probe hybridized with the genes for PSE-1 (CARB-2), PSE-4 (CARB-1), CARB-3 and CARB-4. None of the probes hybridized with genes for any of eight oxacillin-hydrolysing enzymes, PSE-2, OXA-1 to OXA-7, ROB 1 and chromosomal beta-lactamases of various Enterobacteriaceae (except Klebsiella pneumoniae) and Pseudomonas aeruginosa. Investigations of Escherichia coli clinical isolates using these probes indicate the presence of a novel type of extended-spectrum, transferable beta-lactamase. PMID- 1936935 TI - Monoclonal antibody to a specific antigen from Wolinella recta ATCC 33238. AB - Four monoclonal antibodies (m-Abs) to a specific antigen (150-kDa protein antigen) isolated from Wolinella recta ATCC 33238 by acid extraction were obtained. The four antibodies were all of the IgG1 subclass and exhibited equally high specificity for the antigen. A battery of 14 strains or oral bacteria were screened for cross-reactivity with each mAb by ELISA and Western blot analysis. Weak cross-reactivity to some strains was observed which differed depending upon the mAb. Immuno-electromicroscopic studies were performed with a mAb which revealed that the 150-kDa antigen was localized to the cell surface of W. recta ATCC 33238. PMID- 1936936 TI - Sequence of a PAL-related lipoprotein from Bacillus subtilis. AB - The sequence of a small Bacillus subtilis lipoprotein is reported. The gene encodes a protein of 124 amino acids, which shows a low but statistically significant homology to the peptidoglycan-associated lipoproteins (PAL) of Escherichia coli and Haemophilus influenzae. Although the functions of these proteins have not been confirmed, they are obviously structural proteins. In E. coli the gene for the peptidoglycan-associated lipoprotein appears to be essential. PMID- 1936937 TI - The use of bacteriophages of Bacteroides fragilis as indicators of the efficiency of virucidal products. AB - The potential use of bacteriophage B40-8 of Bacteroides fragilis for the evaluation of the virucidal activity of antiseptics or disinfectants was investigated. The antiviral activity of two antiseptics and two disinfectants was evaluated according to a standard guideline. The effect of the virucidal agents was assessed on (i) viruses usually spread by direct contact with surfaces with contaminated secretions, i.e. herpes virus 1 and 2, and vaccinia virus, and (ii) viruses transmitted by the fecal-oral route, i.e. hepatitis A virus, poliovirus, adenovirus and rotavirus. The survival of B40-8 always equalled or exceeded that of the animal viruses tested. Our data suggest the use of bacteriophage B40-8 to complement the information furnished by some standardized methods in ascertaining the antiviral activity of virucidal preparations. PMID- 1936938 TI - Fusion of mycoplasmas: the formation of cell hybrids. AB - Poly(ethylene glycol) (PEG 8000) can induce cell-cell fusion of Mycoplasma capricolum cells, and it can promote the formation of intergeneric hybrids of various Mycoplasma, Acholeplasma and Spiroplasma species. The extent of fusion was quantitatively evaluated by following the dequenching of octadecylrhodamine fluorescent label incorporated into donor cell membranes after their incubation with recipient cells. The results of dequenching experiments were confirmed by electron microscopy, as well as by angle light-scattering measurements. Fusion appeared to require the presence of Mg2+, but was completely inhibited by either 0.1% glutaraldehyde or 100 microM chlorpromazine, and was partially suppressed by proteolytic enzymes, carbonyl cyanide-m-chlorophenylhydrazone, or thiol reagents. PMID- 1936939 TI - Isolation of strains of Thermus aquaticus from the Australian Artesian Basin and a simple and rapid procedure for the preparation of their plasmids. AB - Thirty four Thermus aquaticus strains have been isolated from the non volcanically naturally heated waters of the Australian Artesian Basin which extends the known ecological habitat of this group of organisms. A simple and rapid method developed for isolation of plasmids indicated that considerable variation in numbers and molecular sizes existed within the 23 strains that were investigated. Dissimilar plasmid profiles were obtained from the strains that been isolated from the source waters and those that had been isolated from the runoff channels formed by these source waters. PMID- 1936940 TI - Differentiation of enterococci from other group D streptococci by means of a specific monoclonal antibody. AB - We report on the specificity of a monoclonal antibody which reacts with autoclaved extracts of four species of enterococci but does not react to the same extent with similar extracts from two non-enterococcal group D streptococci. The monoclonal antibody also reacts specifically with purified lipoteichoic acid from Streptococcus faecalis but not significantly with purified lipoteichoic acid from the non-enterococcal species Streptococcus bovis and Streptococcus equinus. The specific antigen detected with this antibody could correlate with the definition of the enterococcus subgroup of the streptococci which would provide further evidence that this sub-group is taxonomically distinct from the other group D streptococci. PMID- 1936941 TI - Mode of membrane insertion and sequence of a 32-amino acid peptide stretch of the penicillin-binding protein 4 of Enterococcus hirae. AB - Analysis of water-soluble derivatives of the Enterococcus hirae 75-kDa membrane bound penicillin-binding protein 4 (PBP4) has yielded the amino acid sequence of a 32-amino acid polypeptide stretch. This peptide is similar to peptide segments known to occur in the N-terminal domain of high-Mr PBPs of class B. The E. hirae PBP4 probably belongs to the same class. It is anchored in the membrane at the N terminus of the polypeptide chain. PMID- 1936942 TI - Two different Escherichia coli capsular polysaccharide depolymerases each associated with one of the coliphage phi K5 and phi K20. AB - The Escherichia coli capsular polysaccharides (K antigens) K5 and K20 are known as primary receptors for the coliphage phi K5 and phi K20, respectively. A host range study of the phage revealed that E. coli K5 strains were not only lysed by phi K5 but also by phi K20, and furthermore that the E. coli K95 test strain was attacked by phi K5 in addition to K5 strains. In order to find out whether the phage can degrade the K antigens, the interaction of the phage with isolated polysaccharides was studied. It could be demonstrated that phi K5 was able to depolymerize the K5 and K95 polysaccharides and that phi K20 showed degrading activity towards the antigens K20 and K5. Obviously, each of the phages was associated with two different enzyme systems which enabled them to recognize and depolymerize chemically unrelated polysaccharides. PMID- 1936943 TI - Transformation of the yeast Saccharomyces kluyveri by Saccharomyces cerevisiae based plasmids. AB - For the transformation of the yeast Saccharomyces kluyveri, ura3 mutants were obtained by 5-fluoro-orotic acid selection. By utilizing the method based on treatment of intact cells with alkali cations, the ura3 strains of S. kluyveri were transformed by Saccharomyces cerevisiae-based plasmids. In the transformed cells, a S. cerevisiae centromere-based plasmid was stably replicated autonomously. Thus, this system will permit the study of gene expression and its regulation in S. kluyveri in relationship to that in S. cerevisiae. PMID- 1936944 TI - A newly described role for protein glycosylation: starved yeast cells absorb their under-glycosylated secreted xylanase faster than the glycosylated enzyme. AB - The yeast Cryptococcus albidus secretes a highly glycosylated xylanase into the culture medium, when grown in presence of xylan, but addition of tunicamycin to the medium results in the formation of an underglycosylated xylanase. Both types of enzyme preparation were incubated with starved yeast cells. Assimilation of the xylanases by the cells over a period of time was followed by electron microscopy using immunolocalization with anti-xylanase antibodies coupled to gold labelled protein A. Electron micrographs showed that the glycosylated enzyme mostly remained attached to the cell wall surface, while the underglycosylated enzyme not only surrounded the cell wall but was also present in the hyaloplasm, indicating its assimilation by the cells. These experiments indicate that the carbohydrate moiety of the xylanase protects the enzyme from its assimilation by the cells producing it. PMID- 1936945 TI - Natural abundance 13C-nuclear magnetic resonance spectroscopic analysis of acyclic polyol and trehalose accumulation by several yeast species in response to salt stress. AB - Analysis of seventeen yeast strains by 13C-NMR spectroscopy has confirmed the significance of glycerol as the sole osmoregulatory solute under salt-stressed conditions, and has shown arabitol to be present in most of the osmotolerant species. Ribitol was detected in some species, including Debaryomyces hansenii, although ribitol accumulation did not correlate with the osmotic pressure of the medium. Relative amounts of arabitol and ribitol decreased in relation to glycerol when the external osmotic pressure was increased. Trehalose was present during exponential growth of some species. PMID- 1936946 TI - The melanophore aggregating response of isolated fish scales: a very rapid and sensitive diagnosis of whooping cough. AB - Pertussis toxin (PT) has been found to block noradrenaline-induced pigment aggregation in fish melanophores, and, based on this, a rapid and highly sensitive assay for PT was developed. Some preliminary results have also indicated that it may be possible to detect PT-like activity in saliva samples from patients with clinically suspected pertussis. In the present study the diagnostic value of the fish melanophore method was evaluated in 70 patients suspected of having pertussis; culture, serology and physician diagnosis were used as reference methods. In 60 of the patients, pertussis was verified by at least one of the reference methods. The melanophore test showed PT-like activity in saliva samples from 58 of the patients. Three patients with reference-verified pertussis showed no PT-like activity in the test; among these, one patient had been immunized and had also been treated with erythromycin during 3 days immediately prior to visiting the hospital. The melanophore test has three major advantages: it allows detection of pertussis in the early and curable stage of the disease; it takes only 2 h to perform; and it requires no sophisticated equipment. PMID- 1936947 TI - Transformation of Aspergillus terreus with the hygromycin B resistance marker from Escherichia coli. AB - Aspergillus terreus was transformed to hygromycin B resistance using a bacterial resistance gene under the control of Aspergillus nidulans regulatory sequences. Southern hybridization of transformants indicated that in most of the cases the vector DNA was integrated into the recipient chromosome in the form of tandem arrays. Transformants were mitotically stable in both selective and non-selective medium and retained their capacity to produce xylanase or glucoamylase activities. PMID- 1936948 TI - Molecular analysis of an essential gene upstream of rpoN in Rhizobium NGR234. AB - Rhizobium sp. NGR234 is a broad-host range strain. The rpoN gene of this organism encodes a sigma factor which is a primary co-regulator of endosymbiosis. We characterized the locus upstream of rpoN, and identified a contiguous open reading frame, here termed ORF1. DNA sequence analysis of this ORF showed that it encoded a polypeptide highly conserved with a corresponding ORF of Rhizobium meliloti. The gene product contained two ATP/GTP binding pockets. Codon usage in the ORF and the nitrogenase operon nifKDH of NGR234 was similar. Although we used a non-transposable cassette flanked by appropriate sized DNA fragments, we were unable to isolate site-directed mutants in the ORF, whose ATP/GTP binding protein product is thus probably of essential biological function. ORF1 and rpoN exhibited conserved linkage among diverse rhizobia, and in Azotobacter vinelandii. Intragenomic and interspecific homology studies confirmed directly that ORF1 (NGR234) belonged to a large family of ATP-binding protein genes. PMID- 1936949 TI - Electrotransformation of Streptococcus pyogenes with plasmid and linear DNA. AB - Electrotransformation was used to introduce both plasmid and linear DNA into Streptococcus pyogenes. The method was optimized using strain NZ131, for which transformation frequencies up to 10(7) per micrograms of plasmid DNA were obtained. A linear fragment of DNA, containing the streptokinase gene (ska) in which an internal fragment had been replaced with an erythromycin resistance gene (erm), was transformed into strain NZ131 with a frequency of 10(3) per micrograms DNA. The introduction of linear DNA into S. pyogenes by electrotransformation should be useful for future genetic analyses as well as targeted gene replacement. PMID- 1936950 TI - Nucleotide sequence of the ethidium efflux gene from Escherichia coli. AB - The nucleotide sequence of the gene specifying the ethidium efflux system of Escherichia coli has been determined. The translated open reading frame has identified a membrane-bound polypeptide of 110 amino acids (11,960 Da) which shares 42% identity with a staphylococcal protein specifying resistance to ethidium. PMID- 1936952 TI - Alfred Henry Sturtevant and crosses between Drosophila melanogaster and Drosophila simulans. PMID- 1936951 TI - Multiple forms of O-methyltransferase involved in the microbial conversion of abietic acid into methyl abietate by Mycobacterium sp. AB - Six out of seven tested strains of mycobacteria transformed abietic acid to methyl abietate in shake culture. The conversion carried out by Mycobacterium sp. MB 3683 was induced by the substrate and stimulated by methionine. Fractionation of the cell extract of Mycobacterium sp. MB 3683 on DEAE cellulose, Ultrogel AcA 44 and MONO Q resulted in the separation of three distinct methyltransferase activities which could also esterify palmitic acid. The separated forms of the methyltransferase exhibited different activities towards these two substrates. PMID- 1936953 TI - Rex and a suppressor of Rex are repeated neomorphic loci in the Drosophila melanogaster ribosomal DNA. AB - The Rex locus of Drosophila melanogaster induces a high frequency of mitotic exchange between two separated ribosomal DNA arrays on a single chromosome. The exchanges take place in the progeny of Rex mothers and occur very early, before the third mitotic division. A number of common laboratory stocks have also been found to carry dominant suppressors of Rex (Su(Rex)). Rex was mapped to the X centric heterochromatin, proximal to su(f), by genetic and molecular analysis of two spontaneous recombinants. Using deficiencies and duplications of the heterochromatin, both Rex and one Su(Rex) were shown to behave as neomorphs. Rex induced exchange in a target chromosome bearing both Rex and Su(Rex) was then used to map these functions to the bb locus itself. Molecular analysis of the recombinants, using length variants of the ribosomal DNA intergenic spacer as genetic markers, mapped Su(Rex) and Rex within the bb locus and demonstrated that both are repeated elements. PMID- 1936954 TI - On the components of segregation distortion in Drosophila melanogaster. V. Molecular analysis of the Sd locus. AB - Segregation Distorter (SD) is a naturally occurring meiotic drive system comprising at least three distinct loci: Sd, Rsp and E(SD). Heterozygous SD/SD+ males transmit the SD chromosome in vast excess over the normal homolog. The distorted transmission involves the induced dysfunction of the spermatids that receive the SD+ chromosome. In the 220-kb region of DNA that contains the Sd gene, we identified a 5-kb tandem duplication that is uniquely associated with all SD chromosomes, absent in SD+ chromosomes, and detectably altered in Sd revertants. On northern blots, genomic probes from the tandem duplication detect an SD-specific 4-kb transcript in addition to several smaller transcripts present in both SD and SD+. Seven classes of cDNAs derived from these transcripts have been isolated. All of these cDNAs share extensive sequence identity at their 3' ends but differ at their 5' ends. Sequence analysis indicates that these cDNAs potentially encode four distinct, but related, polypeptides. Introduction of the tandem duplication into SD+ flies by germline transformation did not confer the dominant gain-of-function Sd phenotype. This result, taken together with our analysis of the Sd cDNAs, suggests that the duplication is part of a much larger gene that encodes several different polypeptides. PMID- 1936956 TI - The ecdysone-induced puffing cascade in Drosophila salivary glands: a Broad Complex early gene regulates intermolt and late gene transcription. AB - The steroid hormone 20-OH ecdysone triggers a classic and well-defined program of chromosome puffing that is assumed to reflect changes in transcriptional activity in Drosophila salivary glands. Mutations in each of four Broad-Complex locus (BR C) complementation groups were analyzed for their effects on the expression of other genes that reside in several major salivary gland puffs. RNA blot analysis showed that the rbp function of the BR-C is required for the transcription of six genes in the 71E late puff and is the first demonstration that an ecdysone induced early gene controls the transcription of late genes within the puffing cascade. In addition, the rbp function is required for the transcription of four intermolt genes (Sgs-3, Sgs-4, Sgs-5 and 71E gene VII). Mutations in the broad, l(1)2Bc and l(1)2Bd functions of the BR-C had no effect on the expression of the genes examined. We propose that the BR-C functions to control transcription at many other salivary gland loci at the beginning of metamorphosis. PMID- 1936955 TI - Perturbation-reperturbation test of selection vs. hitchhiking of the two major alleles of Esterase-5 in Drosophila pseudoobscura. AB - A perturbation-reperturbation tests selective neutrality of 100/100/100/100/100 and 106/100/100/100/100, the two most common alleles at the highly polymorphic X linked locus Esterase-5 in Drosophila pseudoobscura. A total of 22 replicate populations are set up in cages, 11 start at a high frequency of 76% (U) and 11 at a low frequency of 21% (N) of the 106 allele. Allele frequencies change directionally and decrease in both U and N populations as groups and reach equilibria of 60 and 14%, respectively, after 200-300 days. These changes suggest natural selection. A hypothesis of balancing selection accounts for the pattern and predicts a dynamic equilibrium. A rival neutral hypothesis accounts for the pattern equally well by postulating hitchhiking and breakup of linkage leaving the Est-5 variants to drift at neutral equilibria. A reperturbation of allele frequencies in each population, creating 22 additional reperturbed populations EN and EU, with the original populations as controls, directly addresses the question of balancing selection or hitchhiking and breakup of linkage effects. Allele frequencies do not change directionally among the reperturbed populations as a group. The hypothesis of balancing selection is rejected in favor of the hypothesis of initial hitchhiking and dissipated linkage effects. The power of the experimental design to detect selection is studied by simulation. Within the limits of power set by the design, it is concluded that the 100 and 106 are iso fitness alleles of Est-5 under the environmental conditions of the laboratory populations. The requirements of a method of perturbation and reperturbation are discussed. PMID- 1936957 TI - Fine mapping of satellite DNA sequences along the Y chromosome of Drosophila melanogaster: relationships between satellite sequences and fertility factors. AB - The entirely heterochromatic Y chromosome of Drosophila melanogaster contains a series of simple sequence satellite DNAs which together account for about 80% of its length. Molecular cloning of the three simple sequence satellite DNAs of D. melanogaster (1.672, 1.686 and 1.705 g/ml) revealed that each satellite comprises several distinct repeat sequences. Together 11 related sequences were identified and 9 of them were shown to be located on the Y chromosome. In the present study we have finely mapped 8 of these sequences along the Y by in situ hybridization on mitotic chromosome preparations. The hybridization experiments were performed on a series of cytologically determined rearrangements involving the Y chromosome. The breakpoints of these rearrangements provided an array of landmarks along the Y which have been used to localize each sequence on the various heterochromatic blocks defined by Hoechst and N-banding techniques. The results of this analysis indicate a good correlation between the N-banded regions and 1.705 repeats and between the Hoechst-bright regions and the 1.672 repeats. However, the molecular basis for banding does not appear to depend exclusively on DNA content, since heterochromatic blocks showing identical banding patterns often contain different combinations of satellite repeats. The distribution of satellite repeats has also been analyzed with respect to the male fertility factors of the Y chromosome. Both loop-forming (kl-5, kl-3 and ks-1) and non-loop forming (kl-2 and ks-2) fertility genes contain substantial amounts of satellite DNAs. Moreover, each fertility region is characterized by a specific combination of satellite sequences rather than by an homogeneous array of a single type of repeat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936958 TI - Repeated use of GAL1 for gene disruption in Candida albicans. AB - A technique which has the potential to allow repeated use of the same selectable marker to create gene disruptions in Candida albicans has been developed. In this approach, originally described for Saccharomyces cerevisiae, the selectable marker is flanked by direct repeats. Mitotic recombination between these repeats leads to elimination of the selectable marker. A module in which the GALq1 gene is flanked by direct repeats of the bacterial CAT gene was constructed and used to disrupt one copy of the URA3 gene in a gal1 mutant. Gal- revertants were selected by plating on 2-deoxy-D-galactose (2DOG). The frequency of 2DOG resistant colonies recovered was 20 times higher than that obtained with a similar construct not flanked by direct repeats. Of these, 20% had lost the GAL1 gene by recombination between the direct repeats. The GAL1 gene was used again to disrupt the remaining wild-type copy of the URA3 gene of one of these gal1 isolates, resulting in a stable ura3 mutant. This technique should be generally applicable to derive homozygous gene disruptions in this diploid organism. PMID- 1936959 TI - Interallelic complementation among DER/flb alleles: implications for the mechanism of signal transduction by receptor-tyrosine kinases. AB - The large number of available embryonic lethal alleles in the Drosophila EGF receptor homolog (DER)/faint little ball locus allowed us to test the possibility of positive or negative interactions among different DER alleles. These interactions were monitored by examining the embryonic cuticular phenotypes of different heteroallelic combinations. Several positive interactions were identified, while negative interactions were restricted to a single allele. This is the first example of positive interactions within the same cell type among alleles of a receptor tyrosine kinase gene. The basis for these interactions is likely to arise from the mechanism of signal transduction by receptor tyrosine kinases, which involves receptor aggregation. A combination of two different DER mutant proteins defective in temporally distinct stages of the signal transduction process, may thus form a functional heterodimer. The mutation sites in four alleles showing positive interactions were localized. They identify regions within the protein which are likely to be important for these temporally distinct signal transduction processes. PMID- 1936960 TI - The Y chromosome effect on intermale aggression in mice depends on the maternal environment. AB - Two parental strains of laboratory mice, NZB and CBA/H, were chosen for their differences in attack behavior. NZB have higher scores than CBA/H. An effect of the Y chromosome on attack behavior was determined for two maternal environments. Each male was tested once in a dyadic encounter with an A/J male as a standard opponent. The two reciprocal F1s and the four reciprocal backcrosses were used. In each group, the proportion of attacking males was used as the dependent variable. In the first experiment, the ovarian graft method was used to test for an effect of variation of the overall maternal environment: parental vs. F1. The results demonstrated an interaction between the Y chromosome and the maternal environment. By use of the adoption method, it was shown in the second experiment that this maternal effect was probably postnatal (and not prenatal). PMID- 1936961 TI - A novel mouse chromosome 17 hybrid sterility locus: implications for the origin of t haplotypes. AB - The effects of heterospecific combinations of mouse chromosome 17 on male fertility and transmission ratio were investigated through a series of breeding studies. Animals were bred to carry complete chromosome 17 homologs, or portions thereof, from three different sources-Mus domesticus, Mus spretus and t haplotypes. These chromosome 17 combinations were analyzed for fertility within the context of a M. domesticus or M. spretus genetic background. Two new forms of hybrid sterility were identified. First, the heterospecific combination of M. spretus and t haplotype homologs leads to complete male sterility on both M. spretus and M. domesticus genetic backgrounds. This is an example of symmetrical hybrid sterility. Second, the presence of a single M. domesticus chromosome 17 homolog within a M. spretus background causes sterility, however, the same combination of chromosome 17 homologs does not cause sterility within the M. domesticus background. This is a case of asymmetrical hybrid sterility. Through an analysis of recombinant chromosomes, it was possible to map the M. domesticus, M. spretus and t haplotype alleles responsible for these two hybrid sterility phenotypes to the same novel locus (Hybrid sterility-4). Previous structural studies had led to the hypothesis that the ancestral t haplotype originated through an introgression event from M. spretus or a related species. If this were true, one might expect that (1) M. spretus homologs would be transmitted at a non Mendelian ratio within the M. domesticus background, and (2) t haplotypes would be transmitted at a ratio closer to Mendelian within the M. spretus background.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936962 TI - A DNA fragment mapped within the submicroscopic deletion of Ph1, a chromosome pairing regulator gene in polyploid wheat. AB - Bread wheat is an allohexaploid consisting of three genetically related (homoeologous) genomes. The homoeologous chromosomes are capable of pairing but strict homologous pairing is observed at metaphase 1. The diploid-like pairing is regulated predominantly by Ph1, a gene mapped on long arm of chromosome 5B. We report direct evidence that a mutant of the gene (ph1b) arose from a submicroscopic deletion. A probe (XksuS1-5) detects the same missing fragment in two independent mutants ph1b and ph1c and a higher intensity fragment in a duplication of the Ph1 gene. It is likely that XksuS1-5 lies adjacent to Ph1 on the same chromosome fragment that is deleted in ph1b and ph1c. XksuS1-5 can be used to tag Ph1 gene to facilitate incorporation of genetic material from homoeologous genomes of the Triticeae. It may also be a useful marker in cloning Ph1 gene by chromosome walking. PMID- 1936963 TI - Lewontin and Kojima meet Fisher: linkage in a symmetric model of sex determination. AB - The effect of linkage and epistasis on the evolution of the sex-ratio is studied in a symmetric two-locus model of autosomal sex determination closely related to the symmetric viability model of R. C. Lewontin and K. Kojima. R. A. Fisher's expectation of an even sex ratio for autosomal sex determination by a single gene governs the dynamics when the loci are tightly linked. However, recombination may preclude optimization of the sex ratio just as occurs in viability selection models. Many of the evolutionary phenomena known for the symmetric viability model also occur here. In addition, we exhibit a series of new phenomena related to the presence of surfaces of even sex ratio. PMID- 1936964 TI - Mutants affecting processing of DNA in macronuclear development in paramecium. AB - In Paramecium tetraurelia, stock 51, the A surface protein is coded by the wild type A51 gene, present in micronuclei in two copies and in macronuclei in about 1500 copies. DNA processing, comprised of DNA cleavage, copy number amplification and telomere addition occurs at autogamy and conjugation when old macronuclei degrade and new macronuclei are formed from micronuclei. In this paper we characterize mutants with macronuclear A gene deletions. These mutants are notable in three respects. First, the mutants do not appear to be simple micronuclear deletions. Although genetic analysis shows that the d12 mutant d12( 1300) is homozygous for the allele A-1300 and the mutant d12(+1) for A+1, analysis by the polymerase chain reaction indicates that the micronuclei in these two mutants contain intact, but presumably altered, micronuclear A genes. They undergo deletion during DNA processing when new macronuclei are formed. Second, the position of the deletions in these alleles has been shown to change. The deficiency present in the d12 allele A-1300 was originally determined to extend from position -1300 (relative to the start of translation of the A gene) to the end of the chromosome. Later, a derivative of this strain, homozygous for the d12 allele A+1 was isolated in which the start site of the deletion was found to have moved from -1300 to +1. Third, a surprising interaction occurs in crosses between a line homozygous for the d12 allele and one homozygous for the wild-type A51 allele. Previous work on the non-Mendelian d48 mutant (which has intact A51 genes in its micronucleus, but has truncated A51 genes in its macronucleus) has shown that intact A51 alleles must be present in the old macronucleus in order for A51 alleles to undergo proper processing. We find that d12 alleles act on A51 alleles in heterozygotes such that intact macronuclear A genes are no longer required for proper processing of A51. Thus, in crosses of 51 x d12 (either +1 or -1300) d12 exconjugants, as well as 51 exconjugants, give rise to clones carrying both intact A51 and truncated d12 alleles. Remarkably the d12 alleles, which are themselves deleted during processing, are capable in the heterozygote of fostering normal processing of the A51 allele. PMID- 1936967 TI - Food allergy in the 1990s. PMID- 1936966 TI - Mutations in the bli-4 (I) locus of Caenorhabditis elegans disrupt both adult cuticle and early larval development. AB - The bli-4 (I) gene of Caenorhabditis elegans had been previously defined by a single recessive mutation, e937, which disrupts the structure of adult-stage cuticle causing the formation of fluid-filled separations of the cuticle layers, or blisters. We report the identification of 11 new alleles of bli-4, all early larval lethals, including an allele induced by transposon mutagenesis. Nine of the lethal alleles failed to complement the blistered phenotype of e937; two alleles, s90 and h754, complement e937. The complementing alleles arrested development somewhat later than the noncomplementing alleles, which blocked just prior to hatching. We conclude that bli-4 is a complex locus with an essential function late in embryogenesis. We investigated the blistered phenotype of e937 through interactions with other mutations that alter worm morphology or cuticle structure. Recessive and dominant epistasis of several dumpy mutations over the blistered phenotype was observed. Using two heterochronic mutations that alter the developmental stage at which adult cuticle is expressed, we observed that adult worms that lack an adult-stage cuticle could not express blisters. However, late larval worms that expressed the adult cuticle did not express blisters either. It seems likely that the presence of the adult cuticle is necessary, but not sufficient, for blister expression. Blistering resulting from e937 is more severe in trans to null alleles, indicating that e937 is hypomorphic. We postulate that the adult-specific blistering is due to an altered or reduced function of bli-4 gene product in the adult cuticle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936965 TI - Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans. AB - After programmed cell death, a cell corpse is engulfed and quickly degraded by a neighboring cell. For degradation to occur, engulfing cells must recognize, phagocytose and digest the corpses of dying cells. Previously, three genes were known to be involved in eliminating cell corpses in the nematode Caenorhabditis elegans: ced-1, ced-2 and nuc-1. We have identified five new genes that play a role in this process: ced-5, ced-6, ced-7, ced-8 and ced-10. Electron microscopic studies reveal that mutations in each of these genes prevent engulfment, indicating that these genes are needed either for the recognition of corpses by other cells or for the initiation of phagocytosis. Based upon our study of double mutants, these genes can be divided into two sets. Animals with mutations in only one of these sets of genes have relatively few unengulfed cell corpses. By contrast, animals with mutations in both sets of genes have many unengulfed corpses. These observations suggest that these two sets of genes are involved in distinct and partially redundant processes that act in the engulfment of cell corpses. PMID- 1936968 TI - New aspects of diagnosis of milk allergy in children. AB - In clinical practice at present, milk allergy may be suspected by medical history, skin testing, or RAST. None of these procedures has shown an optimal correlation with the result of challenge testing. The obvious need for better diagnostic tests has stimulated numerous attempts to improve the current tests and to develop new ones. The use of individual milk protein fractions for skin testing or RAST has not shown superiority over using whole cow's milk. Lymphoblast transformation and leukocyte inhibition factor production have shown low specificity. The few studies on neutrophil chemotactic activity have shown contradictory results. Morphometric and immunohistochemical studies of small intestinal biopsy specimens seem to be more suitable for research studies than for routine clinical practice. The reliability of in vitro tests on cultured intestinal epithelium remains to be verified and is far from being applicable in clinical practice. The diversity of immunologic mechanisms of milk allergy is largely responsible for the difficulty encountered in developing a highly reliable test in the diagnosis of various reactions to milk allergy. PMID- 1936969 TI - Milk formulae in the prevention of food allergy. AB - Because food allergy is frequent and severe, all possible means should be used to try to prevent its manifestations or at least to delay them until the child is older and stronger and therefore better able to follow an exclusion diet. The capacity of breast-feeding for preventing food allergy has been challenged in the past, but a consensus seems to be emerging now that breast-feeding can indeed prevent food allergy if it is started at birth and is exclusive for at least 4, and preferably 6, months. In the most "at-risk" babies the breast-feeding mother should try to eliminate the most potent allergens (eggs, fish, soya, nuts, and cow's milk) from her diet. If a substitute or a complement to breast milk is necessary, neither goat's milk nor soy milk formula are adequate. Heat treatment alone will not be sufficient to make cow's milk hypoallergenic. Only a combination of protein hydrolysis and managed heat treatment can make cow's milk hypoallergenic and retain its nutritional value. This nutritional value should be assessed by animal studies and also by studying infant growth. The hypoallergenicity of a formula can be studied in vitro and with animal tests, but only clinical trials on human infants will prove its efficacy. PMID- 1936970 TI - Importance of the first meal on the development of cow's milk allergy and intolerance. AB - A cohort of 1749 newborns from the municipality of Odense born during 1985 in the University Hospital of Odense were followed prospectively for the development of cow's milk allergy (CMA)/cow's milk protein intolerance (CMI) during their first year. The diagnosis of CMA/CMI was based on elimination/open milk challenge procedures according to generally accepted criteria. Thirty nine infants (2.2%) developed CMA/CMI. Infants with CMA/CMI were fed cow's milk formula daily during the first month of life significantly more often than infants in the study population (p less than .001). All 39 infants with CMA/CMI had ingested cow's milk formula (40-830 mL) neonatally, whereas none of the 210 neonates without supplements of cow's milk formula developed CMA/CMI (p less than .05). Based on a positive skin-prick test (2+ or more) and/or specific serum IgE antibody to cow's milk (AL-RAST class 2 or more) 16 infants were classified as having CMA. In infants solely breast-fed for greater than 1 month CMA was as frequent (1% [14/1414] as in cow's milk formula fed infant (0.6% [2/335]). In infants with CMI, a significant majority (3.9% [13/335] versus 0.7% [10/1414], p less than .001) had been cow's milk formula fed during the first month. These data indicate an association between early cow's milk formula feeding and development of reproducible adverse reactions to cow's milk protein. Early neonatal intake of cow's milk protein is probably a condition of sensitization and later adverse reactions to cow's milk protein. PMID- 1936971 TI - Does breast-feeding prevent food allergy? PMID- 1936972 TI - Overview of the concept of prevention of allergy. PMID- 1936973 TI - Prediction of allergy in infancy. AB - There is still no test that can predict allergy in infancy with 100% accuracy. For practical purposes, the best we can do is combine a carefully taken family history with a blood sample in early infancy, preferably during the first week of life, on which a sensitive IgE test is applied. If cord blood samples are used, contamination with maternal blood must be avoided as far as possible and samples with high IgE should be checked for possible contamination with maternal blood. Certainly, predictive tests are of no value unless there is a possibility of offering prophylactic measures that prevent or at least delay the onset of the symptoms of allergy. A search for ideal prophylactic measures and screening methods is in progress. PMID- 1936974 TI - Skin test in diagnosis of food allergy. AB - Skin tests have for many years been widely used in the diagnosis of allergic diseases. Standardized allergic tests are commonly available for the diagnosis of inhalant allergy. However food allergens have been studied and no standardized preparations are available. Methods for skin testing vary between regions. In North America, the intradermal skin-test method dominates. On the other hand, pediatricians and Europeans favor the use of skin-prick test, as it is less painful and gives the same information as the intradermal method. Methods for interpretation also vary between regions and groups of doctors. Furthermore, criteria for disease (i.e., presence of food allergy) also varies. Because of the lack of standardized allergen techniques and method, there are difficulties in understanding and using the new data presented in scientific journals. In this article I discuss these difficulties and propose how to handle these problems, concentrating on the skin-prick test method. PMID- 1936975 TI - Variability of pulmonary function tests in stable corticosteroid dependent asthma patients. AB - We studied 24 corticosteroid dependent asthmatic patients over a period of 10 months to establish a baseline for future therapeutic trials with corticosteroid sparing agents. Clinical symptoms, steroid dose, peak expiratory flow rate (PF), forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) were recorded at clinic visits. Correlation was sought between PF and FEV1, steroid dose versus PF and symptom severity, and PF versus time and symptoms. There was considerable weekly variability of PF and FEV1. However, when viewed over almost a year, 54% had no significant change in PF. 29% actually worsened and 17% improved. The data suggest that to assess the effect of a steroid-sparing agent accurately, one must first establish a reliable baseline over several months to eliminate weekly variability. The current trend of obtaining a baseline over a 1 to 2 month interval is inadequate in this study population. We also found that neither patient assessment of severity of symptoms nor corticosteroid dosage correlate with objective spirometric measurements. PMID- 1936978 TI - Do we need the Federation of State, Regional and Local Societies? PMID- 1936976 TI - Chronic cutaneous bacterial hypersensitivity dermopathy: a second case and six year evaluation of the first case. AB - A case we described and reported 6 years ago as chronic cutaneous granulomatous dermopathy was believed due to bacterial hypersensitivity. We now report a second case with similar features of chronic recurrent indolent inflammatory skin lesions, nondiagnostic skin biopsies, and failure to respond to antibiotics. In the absence of another diagnosis and because of the remarkably similar appearance to the first case, we initiated a therapeutic trial with corticosteroids, which induced a remission. The initial case has now been observed for 6 years, and the patient remains in remission on 5 mg of prednisone on alternate days. The second case was considered consistent with bacterial allergy because of IgG and IgE antibodies against common cutaneous bacteria. As there were no granulomas in the current patient's skin lesions, a new designation, chronic cutaneous bacterial hypersensitivity, has been assigned. The differential diagnosis and criteria for this clinical entity are discussed. Either a remission from prednisone or control with low-dose prednisone may be achieved in this dermopathy, which is both disfiguring and frightening to patients. PMID- 1936977 TI - The effect of ketotifen on eosinophils as measured at LTC4 release and by chemotaxis. AB - We examined the effect of ketotifen on calcium ionophore (A23187)-induced leukotriene C4 (LTC4) release from eosinophils, and platelet activating factor (PAF)-induced eosinophil chemotaxis to estimate the mechanism of the antiasthmatic property of ketotifen. Purified eosinophil suspensions were obtained from eight atopic asthmatic subjects and eight normals. Twenty microM of ketotifen significantly inhibited A23187-induced LTC4 release from eosinophils, and 10 microM of ketotifen significantly inhibited PAF-induced eosinophil chemotaxis. These findings may demonstrate the antiallergic pharmacological properties of ketotifen. PMID- 1936979 TI - Zabriskie on peach hairs in hay fever. PMID- 1936980 TI - Hairs of the peach in relation to hay fever. 1887. PMID- 1936981 TI - A Xenopus laevis creatine kinase isozyme (CK-III/III) expressed preferentially in larval striated muscle: cDNA sequence, developmental expression and subcellular immunolocalization. AB - A cDNA containing the nearly complete coding sequence of CK-III subunit of X. laevis was isolated, sequenced and further identified by comparing the tissue distribution of CK-III/III isozyme with that of its messenger. Comparison of CK III deduced amino acid sequence with other CK sequences published reveals its close homology to M-CK subunits. Results using both cDNA probes and monoclonal antibodies specific for CK-III subunits indicate that the appearance and the accumulation of CK-III occur in parallel with myoblast differentiation. Moreover, subcellular immuno-histolocalization shows that CK-III/III isozyme is especially concentrated on larval myofibres at the level of A-bands. PMID- 1936983 TI - Further evidence for the importance of parental source of the Xce allele in X chromosome inactivation. AB - Using mice that were mosaics for both Xce and phosphoglycerate kinase (Pgk-1) alleles, we present further evidence that the parental source of the X chromosome may affect the probability of that X chromosome remaining active. The reciprocal cross differences in PGK-1 activity described here are intermediate between those published previously for other alleles of Xce. PMID- 1936982 TI - Sandy: a new mouse model for platelet storage pool deficiency. AB - Sandy (sdy) is a mouse mutant with diluted pigmentation which recently arose in the DBA/2J strain. Genetic tests indicate it is caused by an autosomal recessive mutation on mouse Chromosome 13 near the cr and Xt genetic loci. This mutation is different genetically and hematologically from previously described mouse pigment mutations with storage pool deficiency (SPD). The sandy mutant has diluted pigmentation in both eyes and fur, is fully viable and has prolonged bleeding times. Platelet serotonin levels are extremely low although ATP dependent acidification activity of platelet organelles appears normal. Also, platelet dense granules are extremely reduced in number when analysed by electron microscopy of unfixed platelets. Platelets have abnormal uptake and flashing of the fluorescent dye mepacrine. Secretion of lysosomal enzymes from kidney and from thrombin-stimulated platelets is depressed 2- and 3-fold, and ceroid pigment is present in kidney. Sandy platelets have a reduced rate of aggregation induced by collagen. The sandy mutant has an unusually severe dense granule defect and thus may be an appropriate model for cases of human Hermansky-Pudlak syndrome with similarly extreme types of SPD. It represents the tenth example of a mouse mutant with simultaneous defects in melanosomes, lysosomes and/or platelet dense granules. PMID- 1936984 TI - Growth hormone and insulin-like growth factor-I measurements in high growth (hg) mice. AB - Effects of a recessive gene causing high growth (hg) were studied on two major components of the growth axis in mice. Plasma and pituitary levels of growth hormone and plasma levels of insulin-like growth factor I (IGF-I) were measured in three lines homozygous for hg, each compared with a control line of alike genetic background but wild type for the hg locus (Hg). Line Gh (hghg) and line GH (HgHg) are from a line which had undergone long-term selection for high postweaning weight gain; line Ch (hghg) and line CH (HgHg) were extracted from the second backcross of Gh to C57BL/6J; line L54 (hghg) was from the sixth backcross to C57BL/6J (B6) (HgHg). Pituitary GH levels and plasma IGF-I levels were measured in both sexes at 3, 4.5, 6 and 9 wk of age. Plasma growth hormone was measured in 8- to 12-wk-old males at hourly intervals from 08.00 to 17.00. Body weight in lines homozygous for hg at 6 and 9 wk of age was 10-30% greater than in control lines. The ontogeny of this increased growth depended on genetic background. Pituitary growth hormone content was 52% lower in the two hghg lines measured (lines Ch and Gh) than in control lines at 4.5, 6 and 9 wk. Plasma growth hormone levels were also much lower in hg mice, with values only 20-30% of those in their respective controls. hg lines showed consistently low plasma growth hormone levels throughout the 9 hr sampling period, while control lines expressed the characteristic pulsatile hormone secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1936985 TI - Population genetics of the Y chromosome of Drosophila melanogaster: rDNA variation and phenotypic correlates. AB - One means of examining the evolutionary significance of molecular variation on the Y chromosome is to identify phenotypes specifically affected by Y-linked genes, and to quantify the phenotypic variation and its correlation to the molecular variation. The functional importance of the Y-linked array of rRNA genes is demonstrated by the ability of Y chromosome to rescue X-linked bobbed lethal alleles, whose lethality is seen in homozygous females. Because low numbers of X-linked rDNA gene copies result in increased developmental time and shortened bristles, and because there is considerable natural variation in Y linked copy number, a careful examination of Y-linked variation in these two traits may uncover a mode of selection acting on the multigene family. In this study, 36 Y-chromosome replacement lines were tested to detect subtle variation in bristle phenotypes and developmental rates. Correlations among these traits, rDNA gene copy number, and intergenic sequence length were quantified. The absence of significant correlations between phenotypic characters and rDNA copy number of intergenic sequence length suggests that the extant molecular variation in Y-linked rDNA can have at most very small selective effects. PMID- 1936986 TI - The mammalian TFIID protein is present in two functionally distinct complexes. AB - The TFIID activity recognizes a TATA-box element and supports formation of an initiation complex containing RNA polymerase II. Antisera specific for the 38-kD human TFIID protein were used to determine whether this protein cofractionated with the TFIID activity. Surprisingly, the TFIID activity in HeLa whole-cell extracts was resolved into two different size complexes, one of 300 kD and one of greater than 700 kD. Cofractionation studies suggest that both complexes contain the 38-kD protein; thus, this component of the large complexes is probably responsible for recognition of the TATA sequence and interaction with the other general transcription factors in formation of the initiation complex. Interestingly, in contrast to the TFIID activity characterized previously, the 300-kD form of TFIID activity, B-TFIID, does not support stimulation of transcription by factors containing acidic or glutamine-rich activating motifs. We propose that the functional and physical differences between these two forms of TFIID activity are caused by differences in the protein composition of the TFIID complexes of which the 38-kD hTFIID protein is an integral part. PMID- 1936987 TI - xUBF contains a novel dimerization domain essential for RNA polymerase I transcription. AB - Xenopus laevis upstream binding factor (xUBF) is an RNA polymerase I transcription factor that is required for formation of the stable initiation complex. The 701-amino-acid protein contains three regions of homology to the chromosomal protein HMG1 (the HMG boxes), which act in comparative independence to cause DNA binding. DNA binding is augmented by a 102-residue amino-terminal domain that causes xUBF to form dimers. The dimerization domain is bipartite in structure, consisting of two regions with the potential to form amphipathic helices, separated by a gap of at least 22 amino acids. The carboxyl half of xUBF is relatively dispensable for transcription (including an 87-residue acidic tail). However, either altering the number of HMG boxes or interfering with dimerization eliminates transcription. The gap region of the dimerization domain is dispensable for dimerization but is absolutely required for transcription. This suggests that the gap region has a critical function in transcription distinct from any effect on dimerization or DNA binding. PMID- 1936988 TI - N-myristoylation is required for function of the pheromone-responsive G alpha protein of yeast: conditional activation of the pheromone response by a temperature-sensitive N-myristoyl transferase. AB - In a screen designed to identify novel mutations in the mating response pathway of Saccharomyces cerevisiae, we isolated conditional alleles of NMT1, the gene encoding N-myristoyl transferase. Genetic data indicate that Nmt1 deficiency results in the activation of the pheromone response at the level of Gpa1, the alpha subunit of the pheromone-responsive G protein. We show that Gpa1 is myristoylated by Nmt1, and without this normally stable modification, Gpa1 is unable to inhibit pheromone signaling. This loss of Gpa1 function is probably not the result of improper subcellular localization. Unlike the mammalian G alpha i proteins alpha i and alpha o, nonmyristoylated Gpa1 is able to associate with membranes. In addition to Gpa1, our data indicate that Nmt1 myristoylates other proteins essential to vegetative growth. PMID- 1936990 TI - Changes in a SWI4,6-DNA-binding complex occur at the time of HO gene activation in yeast. AB - The yeast HO gene is transcribed transiently during G1 as cells undergo START. START-specific HO activation requires two proteins, SWI4 and SWI6, which act via a motif (CACGA4) repeated up to 10 times within the URS2 region of the HO promoter. We identified a DNA-binding activity containing SWI4 and SWI6 that recognizes the CACGA4 sequences within URS2. Two forms of SWI4,6-DNA complexes called L and U can be distinguished by their electrophoretic mobility. L complexes can be detected at all stages of the cell cycle, but U complexes are only detected in cells that have undergone START. The formation of U complexes may be the trigger of HO activation. The SWI6 protein is concentrated in the nucleus throughout G1, but at some point in S or G2 significant amounts accumulate in the cytoplasm. This change in cellular location of the SWI6 protein might contribute to the turnoff of HO transcription after cells have undergone START. PMID- 1936989 TI - The yeast RME1 gene encodes a putative zinc finger protein that is directly repressed by a1-alpha 2. AB - In the yeast Saccharomyces cerevisiae, a/alpha cells can enter meiosis whereas a and alpha cells cannot. The a/alpha cell type is determined by presence of a repressor, a1-alpha 2. Previous studies indicate that a/alpha cells lack an inhibitor of meiosis, the RME1 gene product, and that a and alpha cells express RME1. We report here the sequence of RME1 and functional analysis of its regulatory and coding regions. The 5'-region of RME1 includes a sequence resembling a1-alpha 2 repression sites. Deletion of this site at RME1 relieves repression by a1-alpha 2, and insertion of the site into a heterologous regulatory region (CYC1) confers weak repression in a/alpha cells. These observations indicate that RME1 is directly repressed by a1-alpha 2. The RME1 product has three regions that resemble C2H2 zinc fingers, which are characteristic of a class of nucleic-acid-binding proteins. Substitution of serine for cysteine in each of the putative fingers abolishes RME1 function; serine substitutions in the second and third putative fingers do not affect RME1 stability. These findings indicate that at least two putative zinc fingers are critical for RME1 structure or activity. Therefore RME1, which is formally a negative regulator of the meiotic gene IME1, may act directly as a repressor. PMID- 1936991 TI - The tubB alpha-tubulin gene is essential for sexual development in Aspergillus nidulans. AB - The filamentous fungus Aspergillus nidulans has two genes encoding alpha-tubulin, tubA and tubB. Mutational analysis of tubA has demonstrated that the tubA gene is essential for mitosis and nuclear migration. In this study we have deleted the tubB gene by replacing it with a selectable marker and have named this new allele tubB delta. The results demonstrate that the tubB gene is not required for vegetative growth or asexual reproduction, nor is it required for the initiation or early stages of sexual differentiation. Deletion of tubB, however, completely prevents ascosporogenesis, because tubB delta strains produce no sexual spores when self-crossed. These strains produce viable ascospores when outcrossed to tubB+ strains, indicating that the tubB delta mutation is recessive. We have studied the cytology of sexual development in wild-type strains and in the tubB mutant and have observed that tubB delta. strains develop normally to the stage of ascus formation. However, only a single nuclear mass is observed in the tubB delta ascus, indicating that either the two zygotic haploid nuclei are blocked in karyogamy or that karyogamy occurs but the resulting diploid nucleus is subsequently blocked in meiosis I. PMID- 1936992 TI - Homologous recombination in the tandem calmodulin genes of Trypanosoma brucei yields multiple products: compensation for deleterious deletions by gene amplification. AB - Homologous recombination between a calmodulin-neomycin-resistance fusion gene and the Trypanosoma brucei chromosome takes place not only in the large 5'- and 3' flanking segments of the calmodulin locus but also in any of the four tandem genomic calmodulin genes. This results in a recombined locus consisting of the chimeric neor gene and four, three, two, one, or zero functional calmodulin genes. Cells bearing this latter event have half of their normal number of intact calmodulin genes and an accompanying phenotype of slow growth. Over months of propagation, these lines acquire additional calmodulin genes, frequently by amplifying a calmodulin gene at the untargeted locus, and concomitantly revert to normal growth rate. This response could be related to the property of the trypanosome of maintaining most housekeeping genes in tandem chromosomal arrays. Recombination appears to be initiated by a crossover event between the linearized end of the transfecting plasmid and a homologous region in the host genome; the second crossover generally occurs internally and in that region requires no more than 87 bp of homology. PMID- 1936993 TI - tudor, a posterior-group gene of Drosophila melanogaster, encodes a novel protein and an mRNA localized during mid-oogenesis. AB - The tudor (tud) locus of Drosophila melanogaster is required during oogenesis for the formation of primordial germ cells and for normal abdominal segmentation. The tud locus was cloned, and its product was identified by Northern analysis of wild type and tud mutant RNAs. The locus encodes a single mRNA of approximately 8.0 kb that is expressed throughout the life cycle, beginning in the early stages of germ-line development in the female. During oogenesis, tud mRNA appears to be present in the oocyte precursor within the germarial cysts, and in stages 1-3 it accumulates within the developing oocyte. The transcript is localized to the posterior half of the oocyte during oogenetic stages 4-7 but is not detectable within the ooplasm by egg deposition and throughout early embryogenesis. The tud protein has a predicted molecular mass of 285,000 daltons and has no distinctive sequence similarity to known proteins or protein structural motifs. Taken together, these results indicate that the tud product is a novel protein required during oogenesis for establishment of a functional center of morphogenetic activity in the posterior tip of the Drosophila embryo. PMID- 1936994 TI - Regulation of doublesex pre-mRNA processing occurs by 3'-splice site activation. AB - Sex-specific alternative processing of the doublesex (dsx) pre-mRNA controls somatic sexual differentiation in Drosophila melanogaster. Processing in the female-specific pattern results from the utilization of an upstream 3'-terminal exon and requires the activities of both the transformer (tra) and transformer-2 (tra-2) genes. Use of the more downstream male-specific terminal exons does not require the activities of these genes and is thus considered the default dsx processing pattern. Here, we used transient expression of dsx pre-mRNAs in the presence or absence of tra and tra-2 gene products in Drosophila tissue culture cells to investigate the molecular mechanism controlling this alternative RNA processing decision. These studies reveal that female-specific processing of dsx pre-mRNA is controlled by tra and tra-2 through the positive regulation of female specific alternative 3'-terminal exon use. Delineation of cis-acting sequences necessary for regulation shows that a 540-nucleotide region from within the female exon is both necessary and sufficient for regulation. In addition, utilization of the female-specific 3'-splice site (3'SS) is regulated independently of female-specific polyadenylation. Regulated polyadenylation was obtained only in the presence of splicing, suggesting that activation of female specific exon use occurs by 3'SS activation. PMID- 1936995 TI - Alternative splicing of beta-tropomyosin pre-mRNA: cis-acting elements and cellular factors that block the use of a skeletal muscle exon in nonmuscle cells. AB - The rat beta-tropomyosin (beta-TM) gene encodes both skeletal muscle beta-TM and fibroblast TM-1 by an alternative RNA-splicing mechanism. This gene contains 11 exons. Exons 1-5, 8, and 9 are common to all mRNAs expressed from the gene. Exons 6 and 11 are used in fibroblasts as well as smooth muscle cells, whereas exons 7 and 10 are used in skeletal muscle cells. In this study we have carried out an extensive mutational analysis to identify cis-acting elements that block the use of the skeletal muscle-specific exon 7 in nonmuscle cells. These studies localize the critical elements for regulated alternative splicing to sequences within exon 7 and the adjacent upstream intron. In addition, mutations that inactivate the 5' or 3'-splice sites of exon 6 do not result in the use of the skeletal muscle specific exon 7 in nonmuscle cells, suggesting that splice-site selection in vivo is not regulated by a simple cis-acting competition mechanism but, rather, by a mechanism that inhibits the use of exon 7 in certain cellular environments. In support of this hypothesis we have identified sequence-specific RNA-binding proteins in HeLa cell nuclear extracts using native gel electrophoresis and binding competition assays. Mutations in the pre-mRNA that result in the use of the skeletal muscle exon in vivo also disrupt the binding of these proteins to the RNA in vitro. We propose that the binding of these proteins to the pre-mRNA is involved in regulated alternative splicing and that this interaction is required for blocking the use of the skeletal muscle exon in nonmuscle cells. PMID- 1936996 TI - Attenuation of the heat shock response in HeLa cells is mediated by the release of bound heat shock transcription factor and is modulated by changes in growth and in heat shock temperatures. AB - When HeLa S3 cells are subjected to a continuous 42 degrees C heat shock, activation of heat shock transcription factor (HSF) and transcriptional activation of the heat shock genes hsp70, hsp89 alpha, and hsp60 is transient, peaking at 40-60 min of heat shock, and then attenuating. We have used in vivo genomic footprinting to demonstrate that attenuation of hsp70 transcription is mediated by release of bound HSF from the heat shock element (HSE) of the hsp70 gene promoter. Release of bound HSF in vivo occurs at a higher rate than would be predicted from in vitro measurements of dissociation. Attenuation of HSF activation and heat shock gene transcription occurs only when mild heat shock temperatures are employed (42 degrees C); increasing the heat shock temperature by 1 degree C elicits a much higher level of activation, which does not attenuate during a 4-hr heat shock. Surprisingly, altering the temperature at which cells are grown prior to heat shock modulates the magnitude and temporal pattern of the response to a given heat shock temperature. This finding suggests that HSF does not sense temperature directly but, instead, may be responsive to the magnitude of the difference between growth and heat shock temperatures. PMID- 1936997 TI - tat regulates binding of the human immunodeficiency virus trans-activating region RNA loop-binding protein TRP-185. AB - The TAR element extending from -17 to +80 in the human immunodeficiency virus long terminal repeat (HIV LTR) is required for activation of gene expression by the tat trans-activator protein. TAR RNA forms a stable stem-loop structure, and mutagenesis studies indicate that the stem structure, the primary sequence of the loop, and the bulge element are the major determinants for tat activation. RNA gel retardation analysis demonstrates that both tat and cellular proteins bind to TAR RNA, but the mechanism by which these proteins increase HIV gene expression is unknown. We have fractionated HeLa cell nuclear extracts in an attempt to identify cellular proteins that bind to TAR RNA and are involved in regulating HIV gene expression. RNA gel retardation and UV cross-linking reveal that a cellular protein of 185 kD, which we designate TAR RNA-binding protein 185 (TRP 185), binds with both high affinity and marked specificity to TAR RNA. RNA gel retardation and competition analyses indicate that TRP-185 binding is strongly dependent on the TAR RNA loop sequences. The binding of TRP-185 is modulated by both a set of cellular cofactors and the tat protein. Highly purified preparations of TRP-185 are capable of activating in vitro transcription of wild type, but not mutated, HIV LTR chloramphenicol acetyltransferase (CAT) constructs. These results characterize a positively acting cellular RNA-binding factor, TRP-185, which is involved in the regulation of HIV gene expression. PMID- 1936998 TI - Mixed oligo designer (MOD), a computer program to aid planning of automated, mixed oligodeoxyribonucleotide synthesis for mutagenesis experiments. AB - A computer program, MOD (mixed oligo designer), which aids in planning site directed mutagenesis experiments using highly substituted oligodeoxyribonucleotides (oligos), is described. The program calculates the relationship between the degree of oligo substitution and the mutation frequency, in order to achieve an optimal level of mutagenesis. The program can be used on a wide variety of computers and runs under a number of different operating systems. PMID- 1936999 TI - Transformation of Vibrio cholerae by plasmid DNA. AB - The lack of an efficient transformation system in Vibrio cholerae was a handicap in the genetic manipulation of this important human pathogen. Since V. cholerae cells secrete DNases, this may interfere with the uptake of DNA. The present report describes the approaches taken for transforming V. cholerae cells with plasmid DNA, by overcoming this DNase barrier. The partial success of transforming DNase-negative mutants confirmed the role of DNase in the nontransformability of the wild-type cells. Successful transformation was carried out following removal of DNases from the periplasmic space. This was achieved by treating the cells with Mg2+ and Ca2+ ions to allow the DNase to be released, and then holding them under conditions where the remaining DNase activity was minimized before adding DNA to the competent cells. Transformation efficiencies of the order of 10(-5) per recipient cell were observed. PMID- 1937000 TI - Constitutive expression of cat-86 associated with a change in the transcription start point. AB - The translational attenuation regulatory model suggests a mechanism that can explain the induction of cat-86 by chloramphenicol (Cm). In this model, Cm serves to stall a ribosome at a specific site in a leader region of cat-86 transcripts. The stalled ribosome is thought to destabilize a downstream region of RNA secondary structure that normally sequesters the cat-86 ribosome-binding site (RBS-3). Three mutations in codon 4 of the cat-86 leader have been identified which result in constitutive cat expression. Each of the three mutations generates a likely -10 promoter sequence in the leader. Twenty nucleotides (nt) upstream is the wild-type sequence, 5'-TTGAAA, which differs from the consensus sigA -35 domain by only a single nt. The transcription start point from the resulting mutant promoter is within the DNA region that normally specifies the RNA secondary structure that sequesters cat-86 RBS-3. Thus, the basis for the constitutive phenotype is the absence of the RNA secondary structure in the transcripts driven by the promoter generated through mutagenesis of leader codon 4. PMID- 1937001 TI - Cloning vectors and antibiotic-resistance markers for Brevibacterium sp. R312. AB - Replication of several cryptic plasmids from coryneform strains was investigated in Brevibacterium sp. R312. Only the Corynebacterium glutamicum pSR1 replicon was found to be suitable for establishing a host-vector system. Two pSR1 derivatives, pRPCG200 and pHYCG1, were used as cloning vectors. They carry a neomycin resistance-encoding and a tetracycline-resistance-encoding gene, respectively. PMID- 1937002 TI - Glucose-responsive and oleic acid-responsive elements in the gene encoding the peroxisomal trifunctional enzyme of Candida tropicalis. AB - We have investigated the regulation of expression of the gene (HDE), encoding the peroxisomal trifunctional enzyme hydratase-dehydrogenase-epimerase (HDE), of the diploid yeast Candida tropicalis. Heterologous expression in Saccharomyces cerevisiae of constructs containing deletions in the upstream region of the HDE gene has allowed for determination of regions responsible for the control of expression of the HDE gene. Expression was monitored by immunoblot analysis of yeast lysates with anti-HDE serum. Regions have been identified that are responsible for both repression by glucose and induction by oleic acid. A glucose responsive region lies between nucleotides (nt) -526 and -393. An oleic acid responsive region lies between nt -393 and -341. An additional region controlling derepression by nonfermentable carbon sources is located downstream from nt -341. Comparison of the nt sequences of these regions to upstream regions of other oleic acid-responsive genes of C. tropicalis has identified possible consensus nt sequences for glucose- and oleic acid-responsive upstream elements in these genes. The regulation of the HDE gene in S. cerevisiae closely resembles that found in C. tropicalis, suggesting that similar mechanisms of transcriptional control operate in both yeasts. PMID- 1937003 TI - Sequence of the gene encoding Candida tropicalis peroxisomal trifunctional enzyme. AB - The gene (HDE) encoding the peroxisomal trifunctional enzyme, hydratase dehydrogenase-epimerase, of the yeast Candida tropicalis, was cloned and its nucleotide sequence is reported. PMID- 1937004 TI - Nucleotide sequence of the RAD57 gene of Saccharomyces cerevisiae. AB - We have determined the nucleotide (nt) sequence of the RAD57 gene of Saccharomyces cerevisiae. RAD57 contains an open reading frame of 1380 bp. The deduced amino acid sequence of 460 residues contains a potential nt-binding sequence and shows significant similarity to the preliminary sequence of RAD51. PMID- 1937005 TI - ColE1-type vectors with fully repressible replication. AB - We have constructed two cloning vectors, pAM34 and pAM35, derived from pBR322, in which transcription of the replication primer RNA is under control of the lacZpo promoter/operator. These vectors contain a cloning cassette flanked by strong transcriptional terminators. They differ from each other by the presence (pAM34) or absence (pAM35) of gene lacIq. In the presence of repressor LacIq, replication is entirely dependent upon the addition of inducer. This feature allows the temporary maintenance of these plasmids, the construction of strains in which vector derivatives are stably integrated into the chromosome, and the recovery of nucleotide sequences adjacent to cloned fragments. Replication from the integrated plasmid can be adjusted to match the chromosome replication initiation rate required for cell growth in the absence of a functional origin, oriC. PMID- 1937006 TI - Functional analysis of a C-terminally altered TonB protein of Escherichia coli. AB - Deletions within the 3'-end of the cloned Escherichia coli tonB gene were constructed and recombined into the chromosome. Deletions affecting the last eight C-terminal amino acids (aa) yielded functionally active TonB, whereas deletion of the last 15 C-terminal aa, which removed the C-terminal hydrophobic region of TonB, abolished TonB function entirely. Distribution of TonB within cell compartments was not significantly affected by any of the deletions. All deletion derivatives were less stable than wild-type TonB. A major degradation product of approx. 29 kDa was observed for all TonB derivatives, indicating that it was an N-terminal fragment. The possibility is discussed that the C-terminal hydrophobic region is involved in the intramolecular interaction rather than in the membrane association of TonB. PMID- 1937007 TI - Promoter recognition by the RNA polymerase from vegetative cells of the cyanobacterium Anabaena 7120. AB - The transcription start points (tsp) of seven genes of Anabaena 7120 were previously identified by S1 nuclease protection and primer extension experiments using RNA extracted from cells. In the present work, these tsp were confirmed, with one exception, by in vitro transcription using purified RNA polymerases of Anabaena 7120 and Escherichia coli, and crude extracts of Anabaena 7120 active in transcription. In all cases, the template for transcription consisted of closed circular plasmid DNA in which the putative promoter-containing fragment was cloned in front of a strong terminator, which resulted in defined 'pseudo-runoff' transcripts whose sizes correspond (with one exception) to those expected on the basis of the tsp determined for in vivo RNA. These results, together with others obtained with templates containing bacteriophage T4 or cyanophage N1 promoters, led to the conclusion that the principal Anabaena 7120 RNA polymerase prefers promoters whose sequence and spacing approximate that of the E. coli consensus promoter, and that the Anabaena 7120 genes expressed in vegetative cells, characterized to date, have relatively weak promoters. PMID- 1937008 TI - Low-usage codons in Escherichia coli, yeast, fruit fly and primates. AB - Codon usage is compared between four classes of species, with an emphasis on characterization of low-usage codons. The classes of species analyzed include the bacterium Escherichia coli (ECO), the yeast Saccharomyces cerevisiae (YSC), the fruit fly Drosophila melanogaster (DRO), and several species of primates (PRI) (taken as a group; includes eleven species for which nucleotide sequence data have been reported to GenBank, however, greater than 90% of the sequences were from Homo sapiens). The number of protein-coding sequences analyzed were 968 for ECO, 484 for YSC, 244 for DRO, and 1518 for PRI. Three methods have been used to determine low-usage codons in these species. The first and most common way of assessing codon usage is by summing the number of time codons appear in reading frames of the genome in question. The second way is to examine the distribution of usage in different genes by scoring the number of protein reading frames in which a particular codon does not appear. The third way starts with a similar notion, but instead considers combinations of codons that are missing from the maximum number of genes. These three methods give very similar results. Each species has a unique combination of eight least-used codons, but all species contain the arginine codons, CGA and CGG. The agreement between YSC and PRI is particularly striking as they share six low-usage codons. All six carry the dinucleotide sequence, CG. The eight least-used codons in PRI include all codons that contain the CG dinucleotide sequence. Low-usage codons are clearly avoided in genes encoding abundant proteins for ECO, YSC DRO. In all species, proteins containing a high percentage of low-usage codons could be characterized as cases where an excess of the protein could be detrimental. Low codon usage is relatively insensitive to gross base composition. However, dinucleotide usage can sometimes influence codon usage. This is particularly notable in the case of CG dinucleotides in PRI. PMID- 1937009 TI - Mechanism of high-copy-number integration of pMIRY-type vectors into the ribosomal DNA of Saccharomyces cerevisiae. AB - Targeted integration of the yeast plasmid pMIRY2 into the ribosomal DNA (rDNA) of Saccharomyces cerevisiae by homologous recombination results in transformants carrying 100-200 copies of the plasmid per cell which are stably maintained over a large number of generations [Lopes et al., Gene 79 (1989) 199-206]. These properties make pMIRY2 an attractive vector for high-level production of (heterologous) proteins by yeast cells. We have investigated the mechanism underlying high-copy-number (hcn) integration of pMIRY-type plasmids and show that either targeting to a location outside the rDNA locus or use of the wild type LEU2, instead of the deficient LEU2d gene, as selection marker reduces the copy number to the low value characteristic of standard integrating (YIp-type) yeast plasmids. Further experiments demonstrate that the hcn of pMIRY-type plasmids is achieved by amplification of a small number of copies initially integrated into the rDNA locus. Amplification depends upon the strong selection pressure created by the extremely low expression of the deficient LEU2d gene, but not on the presence of this gene per se. The hcn integration also occurs when either the TRP1 or URA3 gene is used as the selection marker, provided expression of the marker gene is severely curtailed, e.g., by removal of most of its 5' flanking region. PMID- 1937010 TI - Cloning, sequence analysis and transcriptional expression of a ras gene of the edible basidiomycete Lentinus edodes. AB - In the edible basidiomycete, Lentinus edodes, the presence of a high level of intracellular cyclic AMP (cAMP) is closely related to the onset of fruiting and/or primordium formation. Since a close relationship between intracellular cAMP levels and expression of ras genes was reported for organisms such as Saccharomyces cerevisiae and Dictyostelium discoideum, we have cloned and sequences a ras gene homologue from L. edodes (Le.), and analyzed its expression during development of the fungus. This gene, named Le.ras, has a coding capacity of 217 amino acids (aa) interrupted by six small introns. The deduced Le.Ras protein exhibited the highest homology to the Schizosaccharomyces pombe RAS protein (219 aa): 86% homology in the N-terminal 80-aa sequence and 74% homology in the next 80 aa. The Le.ras gene was transcribed at similar levels during mycelial development in fruiting-body formation, suggesting no direct correlation of Le.ras expression with intracellular cAMP levels in this organism. PMID- 1937011 TI - Tetrahymena thermophila acidic ribosomal protein L37 contains an archaebacterial type of C-terminus. AB - We have cloned and characterized a Tetrahymena thermophila macronuclear gene (L37) encoding the acidic ribosomal protein (A-protein) L37. The gene contains a single intron located in the 3'-part of the coding region. Two major and three minor transcription start points (tsp) were mapped 39 to 63 nucleotides upstream from the translational start codon. The uppermost tsp mapped to the first T in a putative T. thermophila RNA polymerase II initiator element, TATAA. The coding region of L37 predicts a protein of 109 amino acid (aa) residues. A substantial part of the deduced aa sequence was verified by protein sequencing. The T. thermophila L37 clearly belongs to the P1-type family of eukaryotic A-proteins, but the C-terminal region has the hallmarks of archaebacterial A-proteins. PMID- 1937012 TI - A new family of repetitive nucleotide sequences is restricted to the genus Zea. AB - We have isolated a new family of moderately repetitive nucleotide sequences (about 2500 copies per haploid genome) specific to the genus Zea and absent in other graminaceous species. These sequences are interspersed in the genome and they show the same genomic organization pattern and similar copy number in all the Zea species examined. These two facts, consistency in the copy number and the same organization pattern, would indicate on the one hand that these sequences were amplified before the divergence of Zea species, and on the other hand that maize and all the teosintes could be considered as the same evolutionary population. Independent clones corresponding to the repetitive sequences have been isolated and sequenced from a genomic library of the teosinte, Zea diploperennis. The repeats, flanked by HaeIII sites, are more than 70% G + C rich, on average 253 bp long and show 78% similarity to each other. These repetitive sequences are in a highly methylated-C context and they present some features resembling those of coding sequences, such as high CpG and low TpA content, and similar codon usage to maize genes in one of the reading frames. Moreover, the repetitive probe hybridizes with RNA extracted from different tissues of maize and from teosinte, indicating that these repeats or similar ones are present in transcribed sequences. PMID- 1937013 TI - Identification of two cell-cycle-controlling cdc2 gene homologs in Arabidopsis thaliana. AB - The cdc2 gene product (p34cdc2) has been thought to play a central role in control of the mitotic cell cycle of yeasts and animals. To approach an understanding of the cell-cycle-control system in higher plants, we isolated, from an Arabidopsis thaliana cDNA library, two clones (CDC2a and CDC2b) similar to the Schizosaccharomyces pombe cdc2 gene. Genomic Southern-blot analysis with the CDC2a and CDC2b cDNA probes suggested that the A. thaliana genome contains several additional cdc2-like genes, which together with the CDC2a and CDC2b genes may constitute a CDC2 gene family. The CDC2a cDNA expressed in Sc. pombe corrected the elongated morphology, caused by the temperature-sensitive cdc2-33 mutation, to the normal shapes, indicating that the A. thaliana CDC2a gene product resembles Sc. pombe p34cdc2 functionally as well as structurally. These results support the view that the cell cycle of higher plants is controlled by an analogue of a p34cdc2-centered regulatory system like that of yeasts and animals. PMID- 1937014 TI - Overproduction of adenovirus DNA polymerase and preterminal protein in HeLa cells. AB - Adenovirus (Ad) DNA polymerase (AdPol) and the preterminal protein (pTP) form a complex that is involved in the in vitro initiation of Ad DNA replication. Recombinant vaccinia viruses (vv) were constructed in which the genes encoding AdPol and pTP were cloned into a vaccinia/T7 hybrid expression-based vector downstream from the T7 promoter (pT7)/encephalomyocarditis virus (EMCV) 5' untranslated region (UTR). HeLa cells infected with the recombinant vv-AdPol or vv-pTP or a mixture of both, together with the vv expressing T7 RNA polymerase produced significant levels of pTP and AdPol which were biologically active in the in vitro initiation of Ad DNA replication. These amounts of pTP and AdPol were only about two-fold less than the levels produced in insect cells infected with the recombinant baculovirus constructs expressing AdPol and pTP. PMID- 1937015 TI - The complex genetic locus polyhomeotic in Drosophila melanogaster potentially encodes two homologous zinc-finger proteins. AB - Differential expression of the homeotic gene complexes, ANT-C and BX-C, of Drosophila melanogaster is partly controlled by trans-regulating factors located outside the two complexes. The complex genetic locus, polyhomeotic (ph), is one of these trans regulators required during development for correct expression of the homeotic selector genes. The ph locus comprises two genetically independent units whose functions are largely redundant. There are two duplicated sequences arranged as a tandem repeat in the ph region, defining two molecular ph units. Sequence analysis of the 28.6 kb of DNA comprising the locus shows varying degrees of sequence conservation between these two molecular units. Long open reading frames with a high degree of conservation have been localized in each tandem repeat. Putative protein products encoded by both the proximal and the distal unit contain several identical or practically identical protein domains: a zinc-finger-forming motif, an alpha-helix motif, a domain rich in serine and threonine residues and stretches of glutamine residues. The presence of these protein domains supports the hypothesis that ph encodes a transcription factor that may function as part of a protein complex. Possible molecular mechanisms leading to the particular structure of the locus are discussed. PMID- 1937016 TI - Production of mouse epidermal growth factor in yeast: high-level secretion using Pichia pastoris strains containing multiple gene copies. AB - We have constructed a synthetic secretion cassette encoding the alpha-factor prepro leader peptide from Saccharomyces cerevisiae fused to mouse epidermal growth factor (mEGF). This was used to compare the secretion of mEGF, a 53-amino acid polypeptide, in S. cerevisiae and Pichia pastoris. In both yeasts the leader sequence was accurately and efficiently cleaved showing that the S. cerevisiae derived alpha-factor prepro region is correctly recognised and processed in P. pastoris. Of the total mEGF produced, over 90% was exported to the culture supernatant, although the final level of accumulation was dependent on the composition of the growth medium. With P. pastoris there was instability of the protein in minimal medium (yeast nitrogen base), probably caused by extracellular proteases. This was overcome by adding 1% Casamino acids and buffering the medium to pH 6.0. To increase the level of secreted mEGF we have developed a method for rapidly screening large numbers of P. pastoris transformants for the presence of many copies of a foreign gene. Using this procedure we isolated a strain containing 19 integrated copies of the mEGF gene which secreted 450 micrograms/ml of mEGF in high-density fermentations. Characterisation of the yeast-derived mEGF showed the presence of truncated forms, mEGF1-51 and mEGF1-52, as was found with S. cerevisiae-secreted human EGF [George-Nascimento et al., Biochemistry 27 (1988) 797-802]. In addition, the full-length protein, mEGF1-53, was secreted by P. pastoris. PMID- 1937017 TI - Production of mouse Hox-2.1 protein in Escherichia coli: characterisation of in vitro binding to DNA. AB - The developmentally regulated mouse Hox-2.1 gene encodes a homeodomain-containing (Hox) protein which is likely to function as a transcription factor. We expressed the DNA coding for full-length Hox-2.1 protein in a T7 promoter-containing vector in bacteria, which produced low levels of protein showing weak DNA-binding activity. Synthesis of a truncated polypeptide lacking all the sequence upstream from the homeodomain enabled us to produce greater amounts of protein and demonstrate its sequence-dependent DNA binding. The tetranucleotide ATTA is necessary for binding, but a single copy is not by itself sufficient. Flanking sequences are important; in particular a cytosine immediately 5' to the ATTA enhances binding. PMID- 1937018 TI - Cloning and expression of a cDNA encoding mouse indoleamine 2,3-dioxygenase. AB - The depletion of an essential amino acid (aa), tryptophan, caused by interferon gamma (IFN-gamma)-mediated induction of indoleamine 2,3-dioxygenase (IDO) in mouse allografted tumor cells, has been suggested as a reason for the allograft rejection. To elucidate the mechanism of this IDO induction, attempts were made to isolate cDNA clones encoding mouse IDO. In seven of 25 mouse cell lines, IDO was induced by IFN-gamma, and the highest IDO induction was observed in the case of rectal cancer (CMT-93) cells, which were further stimulated two- to threefold by the simultaneous addition of dibutyryl cyclic AMP (Bt2cAMP). A cDNA library was prepared from poly(A)+ RNA isolated from CMT-93 cells treated with IFN gamma/Bt2cAMP. The cDNA clones were isolated using the cDNA encoding human IDO as a probe. The mouse IDO cDNA encodes a 407-aa protein with an Mr of 45,639. The deduced aa sequence agreed with partial aa sequences derived from endopeptidase digestion of purified mouse IDO and revealed 61% homology with that of human IDO. Transient expression of the mouse IDO cDNA in COS-7 cells yielded a high level of IDO activity in the cells. Northern hybridization analysis of RNA in CMT-93 cells indicated that IFN-gamma induced the IDO mRNA, and that the level of RNA was increased by simultaneous addition of Bt2cAMP, while Bt2cAMP itself had no effect on mRNA induction. PMID- 1937019 TI - The plasminogen activator family from the salivary gland of the vampire bat Desmodus rotundus: cloning and expression. AB - Complementary DNAs coding for four Desmodus rotundus salivary plasminogen activators (DSPAs) were isolated and characterized. The predicted amino acid sequences display structural features also found in tissue-type plasminogen activator. The largest forms (DSPA alpha 1 and -alpha 2) contain a signal peptide, a finger (F), an epidermal growth factor (EGF), a kringle, and a serine protease domain, whereas DSPA beta and -gamma lack the F and F-EGF domains, respectively. Additional differences between the four forms suggest that distinct genes code for the members of the DSPA family. Transfection of DSPA-encoding cDNAs, placed under the control of the simian virus 40 late promoter, into COS-1 cells resulted in the secretion of highly fibrin-dependent PAs. PMID- 1937020 TI - A new strategy to improve a cauliflower mosaic virus vector. AB - Co-infection of plants with non-overlapping deletion mutants of cauliflower mosaic virus usually leads to the production of the wild-type virus. To prevent this, a pair of mutants with overlapping deletions was constructed. In infected plants both mutant DNAs were stably maintained. Such mutants with overlapping deletions will be used as a vector to overcome the size limitation of genes to be cloned. PMID- 1937021 TI - Synthesis of a wild-type and three mutant Cucurbita maxima trypsin inhibitor encoding genes by a single-strand approach. AB - A single-strand approach to gene assembly, based on a modification of an in vitro complementary oligodeoxyribonucleotide template-directed ligation of the desired sequence to a linearized vector [Chen et al., Nucleic Acids Res. 18 (1990) 871 878], is described. The gene coding for the wild-type Cucurbita maxima trypsin inhibitor of 29 amino acid residues [Bode et al., FEBS Lett. 242 (1989) 285-292], as well as three mutant forms of the gene, in which two of the three disulfide bonds have been replaced singly or as a pair, have been synthesized in a single synthesis run with minimal manual intervention. Subsequent to ligation to pUC9 and in vivo gapped duplex repair by Escherichia coli, their sequences have been verified. PMID- 1937022 TI - Conserved upstream sequence elements in plant 5S ribosomal RNA-encoding genes. AB - As a basis for further comparative studies, nuclear 5S rRNA gene repeats from two plants of the Solanaceae family, tobacco (Nicotiana rustica) and tomato (Lycopersicon esculentum), were isolated and sequenced. The more abundant 5S rRNA gene repeat in tobacco is 430 bp long, while a second less common variant is 521 bp long. In contrast, the 5S rRNA gene repeat from tomato is only 355 bp long. The spacer sequences from these gene repeats, as well as from other published plant nuclear 5S rRNA genes, were compared for repeating or conserved sequence elements. The results indicate that often observed, but non-conserved, repeating sequence elements probably arise spontaneously by unequal crossover with no functional significance. However, three conserved sequence elements immediately upstream of the coding sequence; a C residue at -1, a G + C-rich element centered at -13, and an A + T-rich element centered at -26 resemble regulatory features which have been identified in other types of genes. PMID- 1937023 TI - Nucleotide sequence of the small subunit ribosomal RNA-encoding gene from Opisthorchis viverrini. AB - The complete nucleotide (nt) sequence of the small subunit ribosomal RNA-encoding gene of Opisthorchis viverrini reported in this study is the first nt sequence reported for a trematode. The gene is 1992 nt long and has a G + C content of 50.94%. It is made up of alternated constant and variable regions that are similar to the gene organization of other eukaryotes. It is also of interest to note an unexpectedly high degree of sequence homology between O. viverrini and human genes. PMID- 1937024 TI - Nucleotide sequence of mouse Tcp-1a cDNA. AB - We have isolated complete cDNA clones encoding the mouse t-complex polypeptides 1A and 1B (TCP-1A and TCP-1B) from t-haplotype and wild-type (wt) mice, respectively. The complete nucleotide (nt) sequence of the Tcp-1a cDNA was determined. The Tcp-1a cDNA has an open reading frame (ORF) encoding a 60-kDa protein of 556 amino acids (aa). A comparison of nt sequences between the Tcp-1a and Tcp-1b cDNAs revealed that the 1786-bp regions upstream from their polyadenylation signals differed by 17 substitutions and that Tcp-1a had different polyadenylation sites from Tcp-1b. In these ORFs, 15 bp were substituted between the two alleles, occurring in 14 codons and resulting in eleven single-aa substitutions. Among these 15 substitutions, twelve were nonsynonymous (aa change) and three were synonymous (no aa change). The aa substitution in TCP-1 has occurred at least 20 times faster between t-haplotype and wt than between mouse and human or mouse and Drosophila. PMID- 1937025 TI - Cloning and expression of a cDNA encoding ovine granulocyte-macrophage colony stimulating factor. AB - A cDNA encoding ovine granulocyte-macrophage colony-stimulating factor (GM-CSF) has been cloned using the polymerase chain reaction. The nucleotide sequence is approx. 93% identical to the published bovine GM-CSF-encoding sequence, 84% to the human sequence and 73% to the murine sequence. The deduced amino acid sequence of the ovine GM-CSF protein was found to be 80% identical to both the human and bovine proteins and 57% to the murine protein. Transient expression of recombinant ovine GM-CSF in COS-1 cells was obtained and its biological activity investigated in a bone-marrow colony-forming assay. Ovine GM-CSF was found to promote the formation of granulocyte-macrophage colonies as well as eosinophil, neutrophil and monocyte/macrophage colonies, an activity characteristic of GM-CSF in other species. Recombinant human GM-CSF was found to have no proliferative effect on ovine bone-marrow cells. PMID- 1937026 TI - Sequence of a 1.4-kb region in the 3'-flanking region of the murine c-fos proto oncogene which contains an estrogen-response element. AB - The nucleotide sequence of a 1.4-kb region in the 3'-flanking region of the murine c-fos oncogene has been determined. This region contains an estrogen response element which is located almost 5 kb downstream from the c-fos promoter. PMID- 1937027 TI - Sequence analysis of the variable region of a mouse gene encoding a monoclonal anti-idiotypic antibody that detects a restricted idiotype on anti-HIV-1 gp160. AB - We have sequenced the cDNAs encoding the variable (V) regions from the light and heavy chains of a monoclonal anti-idiotypic antibody (Ab), designated MC1, that, when used as an immunogen, activates regulatory idiotypes associated with anti HIV-1 gp 160 responses. This anti-Id represents a non-antigen-mimicking subclass of Ab-2 referred to as non-internal image. The gene family selections and sequence homologies are presented. PMID- 1937028 TI - Analysis of the promoter region of the housekeeping gene DmRP140 by sequence comparison of Drosophila melanogaster and Drosophila virilis. PMID- 1937029 TI - Phage T4 expression vector: protection from proteolysis. AB - We have developed an efficient method for the expression of heterologous genes during infection by T4, a bacteriophage known to inhibit the proteolytic systems of Escherichia coli. This system enables us to clone genes in a plasmid expression vector and move them readily into T4. We have used lacZ as a reporter gene to show that both plasmid and phage exhibit low basal expression or high level expression under the control of a T7 promoter. This system promises a possible solution to the problem of degradation and/or toxicity of overproduced proteins. PMID- 1937030 TI - Development of a novel Bacillus subtilis cloning system employing its neutral protease as screen marker. AB - Part of the pUC19 polylinker sequence (33 bp) was inserted into the pro-peptide coding region of the Bacillus subtilis neutral protease-encoding gene to replace a 93-bp FspI-HindIII fragment. This in-frame sequence replacement had little effect on the expression and secretion of the neutral protease. This plasmid can therefore be used as a cloning vector, and recombinant clones can be directly identified on skim milk indicator plates by the loss of a clear ring (or halo) around the colonies. This novel cloning system offers several advantages over existing B. subtilis cloning vectors: (i) convenient direct screening of recombinants; (ii) the use of inexpensive indicator; (iii) no restriction on the use of host strains; and (iv) the availability of seven frequently used unique cloning sites: BamHI, XbaI, SalI, PstI, SphI, HindIII, and EcoRI. This system also has the potential to be used as an expression/secretion vector. PMID- 1937031 TI - Sequence analysis of the cellulase-encoding celY gene of Erwinia chrysanthemi: a possible case of interspecies gene transfer. AB - The Erwinia chrysanthemi (strain 3937) celY gene encoding the minor endoglucanase (EGY) was sequenced. The analysis of the upstream region allowed us to identify an in vivo active promoter recognized by the NtrA (sigma 54) holoenzyme. No similarity was found between the predicted amino acid (aa) sequences of EGY and either the Er. chrysanthemi major endoglucanase, EGZ, or the Er. carotovora CelS endoglucanase. In contrast, a very high level of identity, both at the nucleotide and the predicted aa levels, was found between celY and an EG-encoding gene from Cellulomonas uda, a Gram + bacterium taxonomically distant from Er. chrysanthemi. By comparing the molar G + C% of the cellulase-encoding genes and that of Er. chrysanthemi and C. uda chromosomal DNAs, we speculate that celY was transferred from Er. chrysanthemi to C. uda. PMID- 1937032 TI - Isolation, sequence and expression in Escherichia coli, Bacillus subtilis and Lactococcus lactis of the DNase (streptodornase)-encoding gene from Streptococcus equisimilis H46A. AB - A partial library of BclI-generated chromosomal DNA fragments from Streptococcus equisimilis H64A (Lancefield Group C) was constructed in Escherichia coli. Clones displaying either streptokinase or deoxyribonuclease (streptodornase; SDC) activities were isolated. The gene (sdc) expressing the SDC activity was allocated on the 1.1-kb AccI DNA subfragment. Sequence analysis of this DNA fragment revealed the presence of one open reading frame, which could encode a protein of 36.8 kDa. The N-terminal portion of the deduced protein exhibited features characteristic of prokaryotic signal peptides. The sdc gene was expressed in E. coli, Bacillus subtilis and Lactococcus lactis. As observed for S. equisimilis, in the heterologous Gram + hosts, at least part of the SDC protein was secreted into the medium. PMID- 1937033 TI - High-efficiency yeast artificial chromosome fragmentation vectors. AB - Chromosome fragmentation vectors (CFVs) are used to create deletion derivatives of large fragments of human DNA cloned as yeast artificial chromosomes (YACs). CFVs target insertion of a telomere sequence into the YAC via homologous recombination with Alu repetitive elements. This event results in the loss of all YAC sequences distal to the site of integration. A new series of CFVs has been developed. These vectors target fragmentation to both Alu and LINE human repetitive DNA elements. Recovery of deletion derivatives is ten- to 20-fold more efficient with the new vectors than with those described previously. PMID- 1937034 TI - Promoter structure and expression of the 3-phosphoglycerate kinase-encoding gene (pgk1) of Trichoderma reesei. AB - Transcription of the 3-phosphoglycerate kinase (PGK)-encoding gene (pgk1) of Trichoderma reesei results in two transcripts due to two main transcription start points (tsp) which are differentially regulated during the growth cycle. The nucleotide sequence of the promoter reveals a number of putative regulatory elements present also in the PGK promoter of Saccharomyces cerevisiae: a 20-nt long sequence similar to the CTTCC-repeat region of the upstream activating sequence UAS, the eukaryotic heat-shock consensus sequence, HSE, and a putative eukaryotic cAMP regulatory sequence. The functionality of the putative HSE sequence was examined, but no clear effect could be seen on the total amount of pgk1 mRNA at elevated temperatures nor on transcription initiation from the upstream tsp, preceded by the HSE sequence. PMID- 1937035 TI - Sequence of the downstream flanking region of the shape-determining genes mreBCD of Escherichia coli. AB - The nucleotide sequence of the downstream flanking region of the mreD gene of Escherichia coli was determined. Two open reading frames (ORFs) were found, a 591 bp orfE and a 1467-bp orfF. Based on the sequence, it is suggested that the three mre genes (encoding the murein pathway), mreB, mreC and mreD, and these two ORFs possibly form an operon. PMID- 1937036 TI - Sequence of the gene encoding the major outer membrane protein of the mouse pneumonitis biovar of Chlamydia trachomatis. AB - The gene encoding the major outer membrane protein of the Chlamydia trachomatis mouse pneumonitis biovar was sequenced and the amino acid sequence deduced. The primary structure of this protein is similar to that of the lymphogranuloma venereum and trachoma biovars in that it consists of four variable domains interspersed with five constant domains. This protein may be an ideal candidate for a vaccine in chlamydia-infected mouse experimental models. PMID- 1937037 TI - A yeast chromosomal fragment having strong promoter activity in Escherichia coli. AB - We have identified a yeast fragment that has strong promoter activity in Escherichia coli. The sequence analysis has shown that this fragment contains E. coli promoter consensus sequence and translation initiation signals required to express an in-frame lacZ alpha product. PMID- 1937038 TI - An in vitro coupled transcription-translation system from Staphylococcus aureus. AB - We have developed a Staphylococcus aureus cell-free system that is capable of directing DNA-dependent synthesis of proteins. The staphylococcal plasmids pE194 and pSK265 were used to characterize this system. The in vitro system was found to direct the synthesis of the appropriate proteins predicted from the nucleotide sequence of the plasmids. As is the case in vivo, low levels of the inducer, erythromycin, promoted the synthesis of the pE194-encoded ribosomal RNA methyltransferase in the in vitro system. PMID- 1937039 TI - An androgen-inducible expression system for Saccharomyces cerevisiae. AB - A novel controllable expression system for Saccharomyces cerevisiae has been developed. Expression of the gene encoding the human androgen receptor, from a strong yeast promoter, results in transactivation of a hybrid promoter carrying androgen-responsive sequences such that a target gene may be expressed in an androgen-dependent manner. By selection of an appropriate combination of androgen receptor level, target-gene copy number and concentration of the androgenic ligand, dihydrotestosterone, the expression level can be set within a 1400-fold range with no detectable effect on normal cell growth. PMID- 1937040 TI - The isolation and characterization of a calmodulin-encoding gene (CMD1) from the dimorphic fungus Candida albicans. AB - Candida albicans is a dimorphic, opportunistic pathogen of humans, and calcium and calmodulin have been implicated in its morphogenic transition. The C. albicans calmodulin-encoding gene, CMD1, was isolated from cDNA and genomic phage lambda libraries using the Saccharomyces cerevisiae CMD gene as a hybridization probe. Southern-blot hybridization analysis of genomic DNA suggests the existence of only one type of calmodulin gene in C. albicans. Comparison of cDNA and genomic sequences identified a 222-bp intron located immediately after the Met start codon. The predicted amino acid sequence was 60% identical with yeast CMD and 70% identical with CMDs of filamentous fungi and vertebrates. We have localized the CMD1 gene to chromosome 3 using the contour-clamped homogeneous electric field gel electrophoresis. The CMD1 gene hybridized to a single 650 nucleotide transcript which was present in equivalent amounts in both the yeast and hyphal forms of the organism. PMID- 1937041 TI - Characterization of a second alkane-inducible cytochrome P450-encoding gene, CYP52A2, from Candida tropicalis. AB - A second alkane-inducible cytochrome P450-encoding gene (CYP52A2) from the yeast Candida tropicalis was sequenced and characterized. CYP52A2 is located 1 kb upstream from CYP52A1, the previously characterized P450 gene [Sanglard and Loper, Gene 76 (1989) 121-136] and shows the same orientation. Like CYP52A1, CYP52A2 is induced by growth on alkane. Both promoter regions share repeats of the sequence CATGTGAA that could be of importance for the induction of the two genes. At the amino acid level, alk2 shows an overall identity of 68.2% and an overall similarity of 81.6% to alk1. Regions of high homology between the two proteins are found in the distal and proximal heme binding sites which contain the highly conserved cysteine residue as the fifth ligand to the heme iron. However, marked differences between the two proteins exist at their N-terminal end, which includes the transmembrane domain, and at the putative substrate binding domain. Upon expression of CYP52A2 in Saccharomyces cerevisiae, alk2 was shown to hydroxylate hexadecane, but had no hydroxylation activity towards lauric acid, whereas alk1 showed both activities. Comparative immunoblots demonstrate that neither alk1 nor alk2 expressed in S. cerevisiae corresponds to the main cytochrome P450 present in C. tropicalis when grown on alkane. PMID- 1937042 TI - Sequences of two tandem genes regulated by carbon sources, one being essential for n-alkane assimilation in Candida maltosa. AB - Several n-alkane-inducible clones were isolated from the genomic library of an n alkane-assimilation yeast, Candida maltosa, by the differential hybridization method. Among these, one of the most predominantly expressed clones was analyzed. The nucleotide sequence of the cloned DNA fragment showed that it contained two open reading frames, one encoding a protein of 127 amino acids (aa) and the other a protein of 276 aa. The former was named POX18Cm, because the sequence was highly homologous to that of the Candida tropicalis gene, POX18, which already had been identified as encoding a small oleate-inducible peroxisomal protein. The latter, named ALI1, had no homologous sequences in the EMBL database (1990 release). Northern-blot hybridization indicated that the expression of these two genes was regulated by carbon sources in the media. From gene-disruption experiments, it was concluded that ALI1 was essential for assimilation of n alkane by C. maltosa. PMID- 1937043 TI - Combinatorial mutagenesis of three major groove-contacting residues of EcoRI: single and double amino acid replacements retaining methyltransferase-sensitive activities. AB - A library of mutant ecoRIR genes encoding EcoRI restriction endonuclease was generated using trinucleotide blocks and a combination of recombinant DNA procedures, including primer extension and the polymerase chain reaction. Codons corresponding to three amino acids (E144, R145 and R200), previously implicated in the specific recognition of the DNA substrate, were combinatorially mutated so as to generate a library that potentially contains all 20(3) possible single, double and triple aa replacements, in a balanced distribution. Inspection of the phenotypes of Escherichia coli colonies bearing the mutant genes showed that several of them retained activities that were deleterious to the cells but were still protected by the EcoRI methyltransferase. These included new enzyme variants, including non-conservative single (Thr or Val for Glu144) and double (Val for Glu144 and Thr for Arg145) replacements. PMID- 1937044 TI - Characterization and expression of a genomic pectin methyl esterase-encoding gene in Aspergillus niger. AB - The genomic pectin methylesterase (PME)-encoding gene (pmeA) from Aspergillus niger strain RH5344 was cloned by probing a genomic DNA library with a cDNA coding for PME. The recombinant phage clone was isolated and a 6-kb HindIII fragment was subcloned and characterized. The gene consists of seven exons and six introns. The nucleotide sequences of the coding regions were identical to those found in the pmeA cDNA. Cotransformation of A. niger was achieved with the vector, pAN7-1, and transformants were then tested for PME production. Transformants which produced more PME than the untransformed recipient strain were subjected to Southern-blot and Northern-blot analysis. The results show that there is a reasonable correlation between gene copy number, mRNA levels and PME production. PME was produced by A. niger transformants in an active 43-kDa form, which is similar to that of the mature protein isolated from the strain, RH5344. On the basis of the results of affinity labeling of PME with sugar-specific lectins and the amino acid sequence data, it has been revealed that PME is a glycoprotein and the protein-bound glycans are oligosaccharides with a high mannose content. PMID- 1937045 TI - Cloning, sequence and characterization of m5C-methyltransferase-encoding gene, hgiDIIM (GTCGAC), from Herpetosiphon giganteus strain Hpa2. AB - We have cloned the gene (hgiDIIM) encoding the methyltransferase (MTase) of the SalI isoschizomeric restriction-modification (R-M) system, HgiDII (GTCGAC), into Escherichia coli. The hgiDIIM gene has been isolated from the same plasmid library of Herpetosiphon giganteus strain Hpa2, as was the previously cloned R-M system, HgiDI [AcyI/GRCGYC; Dusterhoft et al., Nucleic Acids Res. 19 (1991) 1049 1056]. Sequencing and functional localization of hgiDIIM revealed an open reading frame (ORF) of 354 codons (39786 Da) with significant homologies to the group of m5C-, rather than the m4C-/m6A-, MTases. Subsequent cloning and analysis of adjacent chromosomal segments led to the identification of two additional ORFs upstream (ORF15, 139 codons) and downstream (ORF68, 611 codons) from hgiDIIM with the same transcriptional orientation as the hgiDIIM gene. However, the expected restriction enzyme function was not found in either of these ORFs. PMID- 1937046 TI - Production of hepatitis B virion-like particles in yeast. AB - We constructed a yeast strain that simultaneously expresses four genes encoding the major S, middle S, large S hepatitis B viral envelope proteins and the core protein under the control of the yeast glyceraldehyde-3-phosphate dehydrogenase promoter and terminator. The lysate from this cell line, examined by immunological, physicochemical methods and electron microscopy, was found to contain spherical particles with a diameter of about 40 nm and a density of 1.25 g/ml. These particles reacted with anti-envelope antibodies, but not with anti core antibodies. However, core antigenicity appeared upon treatment with 3% Nonidet P-40 that eliminates an outer envelope. These observations suggest production of a virion-like complex structure, or at least its DNA-less analog, consisting of core particle enveloped by antibody-reactive envelope. Such a structure was made only when all the four gene products were synthesized in a yeast cell. This system may be useful for the study of virus structure and assembly, and for improved vaccine development. PMID- 1937047 TI - High-level secretion of the extracellular domain of the human growth hormone receptor using a baculovirus system. AB - A chemically synthesized gene (hGHR-ED) coding for the extracellular domain (ED) of the human growth hormone (hGH) receptor (hGHR) was inserted into the genome of Autographa californica nuclear polyhedrosis virus adjacent to the polyhedrin promoter. Spodoptera frugiperda cells infected with the recombinant virus secreted a protein with hGH-binding activity into the medium. The secreted 35-kDa protein was purified to near homogeneity. The purified protein exhibited a high binding affinity (Kd = 0.2-0.3 nM) to hGH. The highest cell production capability was estimated at more than 10-20 micrograms hGHR-ED/ml of culture. The inhibition of the hGHR-ED secretion by treatment with tunicamycin suggests that glycosylation is important for secretion. PMID- 1937048 TI - CpG islands: features and distribution in the genomes of vertebrates. AB - We have investigated the distribution of unmethylated CpG islands in vertebrate genomes fractionated according to their base composition. Genomes from warm blooded vertebrates (man, mouse and chicken) are characterized by abundant CpG islands, whose frequency increases in DNA fractions of increasing % of guanine + cytosine; % G + C (GC), in parallel with the distribution of genes and CpG doublets. Small, yet significant, differences in the distribution of CpG islands were found in the three genomes. In contrast, genomes from cold-blooded vertebrates (two reptiles, one amphibian, and two fishes) were characterized by an extreme scarcity or absence of CpG islands (detected in these experiments as HpaII tiny fragments or HTF). CpG islands associated with homologous genes from cold- and warm-blooded vertebrates were then compared by analyzing CpG frequencies, GC levels, HpaII sites, rare-cutter sites and G/C boxes (GGGGCGGGGC and closely related motifs) in sequences available in gene banks. Small, yet significant, differences were again detected among the CpG islands associated with homologous genes from warm-blooded vertebrates, in that CpG islands associated with mouse or rat genes often showed low CpG and/or GC levels, as well as low numbers of HpaII sites, rare-cutter sites and G/C boxes, compared to homologous human genes; more rarely, CpG islands were just absent. As far as cold blooded vertebrates were concerned, a number of genes showed CpG islands, which exhibited a much lower frequency of CpG doublets than that found in CpG islands of warm-blooded vertebrates, but still approached the statistically expected frequency; none of the other features of CpG islands associated with genes from warm-blooded vertebrates were present. Other genes did not show any associated CpG islands, unlike their homologues from warm-blooded vertebrates. PMID- 1937049 TI - CpG islands, genes and isochores in the genomes of vertebrates. AB - We have shown that human genes associated with CpG islands increase in number as they increase in % of guanine + cytosine (GC) levels, and that most genes associated with CpG islands are located in the GC-richest compartment of the human genome. This is an independent confirmation of the concentration gradient of CpG islands (detected as HpaII tiny fragments, or HTF) which was demonstrated in the genome of warm-blooded vertebrates [Aissani and Bernardi, Gene 106 (1991) 173-183]. We then reassessed the location of CpG islands using the data currently available and confirmed that CpG islands are most frequently located in the 5' flanking sequences of genes and that they overlap genes to variable extents. We have shown that such extents increase with the increasing GC levels of genes, the GC-richest genes being completely included in CpG islands. Under such circumstances, we have investigated the properties of the 'extragenic' CpG islands located in the 5'-flanking segments of homologous genes from both warm- and cold-blooded vertebrates. We have confirmed that, in cold-blooded vertebrates, CpG islands are often absent; when present, they have lower GC and CpG levels; the latter attain, however, statistically expected values. Finally, we have shown that CpG doublets increase with the increasing GC of exons, introns and intergenic sequences (including 'extragenic' CpG islands) in the genomes from both warm- and cold-blooded vertebrates. The correlations found are the same for both classes of vertebrates, and are similar for exons, introns and intergenic sequences (including 'extragenic' CpG islands). The findings just outlined indicate that the origin and evolution of CpG islands in the vertebrate genome are associated with compositional transitions (GC increases) in genes and isochores. PMID- 1937050 TI - De novo purine nucleotide biosynthesis: cloning, sequencing and expression of a chicken PurH cDNA encoding 5-aminoimidazole-4-carboxamide-ribonucleotide transformylase-IMP cyclohydrolase. AB - The purH cDNA, encoding 5-aminoimidazole-4-carboxamide-ribonucleotide (AICAR) transformylase-inosine monophosphate cyclohydrolase (ATIC), was cloned by functional complementation of an Escherichia coli purH mutant using a chicken liver cDNA expression library. This represents the first report of the cloning of any eukaryotic ATIC-encoding cDNA (PurH). The avian ATIC mRNA is 2.3 kb long and encodes a protein with an Mr of 64,422. The deduced amino acid sequence is 36% identical to the bacterial purH-encoded enzymes from Bacillus subtilis and E. coli. The avian cDNA was expressed as a glutathione S-transferase (GST) fusion protein that was purified in a single step by affinity chromatography. A novel vector was employed which permits rapid and highly efficient cleavage of the GST fusion protein yielding 10 mg of purified PurH product per liter of bacterial culture. Km values were determined with the purified fusion protein utilizing AICAR and (6-R)N10-formyl-tetrahydrofolate as substrates. These values compare favorably with the isolated avian enzyme, supporting the idea that kinetic, as well as other physical properties of the recombinant fusion protein are similar to the native avian enzyme. Large quantities of purified enzyme and the ability to generate site-directed mutations should make mechanistic studies possible. The recombinant enzyme also affords a simple and reliable approach to identifying new antifolates. PMID- 1937051 TI - A zinc finger protein-encoding gene expressed in the post-meiotic phase of spermatogenesis. AB - Spermatogenesis is the complex series of physiological and morphological changes that occur when spermatogonial stem cells differentiate into mature spermatozoa. Some of these changes are likely to be regulated at the level of transcription. To approach this problem, we have cloned a cDNA from mouse testis, encoding a protein (Zfp-29) with 14 copies of the zinc finger (Zf) motif commonly found in transcriptional regulatory proteins. The expression of this gene, Zfp-29, is restricted to the testis in adult mice, but also occurs during embryonic development. Within the testis, Zfp-29 mRNA is enriched in round spermatids, the earliest post-meiotic cells. Thus, the putative Zfp-29-encoded protein may have a role in regulating the class of genes that are expressed in post-meiotic germ cells. PMID- 1937052 TI - The TATA-dependent and TATA-independent promoters of the Drosophila melanogaster actin 5C-encoding gene. AB - The major cytoskeletal actin of Drosophila melanogaster, actin 5C, is encoded by a gene (act5C) that has two promoters which are differentially controlled and possess distinct sets of regulatory elements. The distal basal promoter has a TATA motif, but the proximal does not. The distal strong positive domain, centered at nucleotide -290, can be shifted and fused directly to the distal basal promoter without losing its activity. It can also activate heterologous basal promoters containing either TATAAAT or TATTTAA signal when directly fused to them, but cannot activate the basal proximal promoter, which is TATA-less. When the entire distal regulatory region, which includes a remote enhancer-like region, is fused to the proximal promoter, it does not increase the proximal promoter activity. Fusion of the distal strong negative domain to the proximal promoter does not inhibit activity. Thus, all the three major strong regulatory domains of the distal promoter are unable to act on the proximal promoter. PMID- 1937053 TI - Murine retroviral vectors expressing the tax1 gene of human T-cell leukemia virus type 1. AB - Murine retroviral vectors which express the tax1 gene of human T-cell leukemia virus type 1 (HTLV-1) have been constructed. A significant increase in virus titer was achieved by inserting a portion of the gag region of Moloney murine leukemia virus. Using these vectors, tax1 was stably introduced into primary human T-cells derived from peripheral blood lymphocytes. Expression of the functional tax1 in infected cells was confirmed by trans-activation of HTLV-1 long terminal repeat-directed transcription. These vectors provide a useful means of investigating the function of tax1 in natural target cells for HTLV-1. PMID- 1937054 TI - Characterization of the gene encoding the salivary Gln/Glu-rich C-terminal variant A protein. AB - The rat submandibular gland-specific GRP-Ca gene (encoding C-terminal variant A of the glutamine/glutamic acid-rich protein) has been cloned from a male Wistar/Furth genomic library. The complete sequence, including 2.0 kb of 5' flanking and 0.5 kb of 3' flanking DNA has been determined. Electron microscopic heteroduplex analysis and sequence analysis established that transcripts coding for GRP-Ca and GRP-Cb are encoded by separate genes. The GRP-Ca gene is approx. 4.5 kb in size and is comprised of four exons and three introns. Comparison of this gene with several rodent and human salivary proline-rich protein-encoding genes (PRP) indicates that GRP-Ca shares this exon-intron structure with the rat SMR-2 gene, the hamster H29 gene, and the human PRP genes. In addition, a 28-bp element found in the proximal promoter region of GRP-Ca was found to be highly conserved among the superfamily of PRP genes. PMID- 1937055 TI - Secretion of human epidermal growth factor from Saccharomyces cerevisiae using synthetic leader sequences. AB - We have investigated different leader sequences for their ability to direct the efficient secretion of human epidermal growth factor (hEGF) from Saccharomyces cerevisiae. We designed a consensus signal sequence which directs secretion of hEGF from yeast as efficiently as the yeast invertase signal sequence. However, secretion is increased over fivefold by the introduction, after the signal sequence, of a synthetic 19-amino acid (aa) pro-sequence containing a cleavage recognition site for the KEX2 protease. Even in the absence of an Asn-linked glycosylation site, secretion of hEGF using the synthetic prepro-leader was as efficient as that directed by the alpha-factor leader. The role of the KEX2 protease cleavage site was investigated by mutation of the yeast alpha-factor KEX2 site (cleavage after Lys-Arg). Cleavage was obtained with the following order of efficiency, Lys-Arg greater than Pro-Arg greater than Asp-Arg, although the sequence context was also found to affect efficiency. PMID- 1937056 TI - Chimerization of antibodies by isolation of rearranged genomic variable regions by the polymerase chain reaction. AB - We describe a new method for amplification, by polymerase chain reaction (PCR), of rearranged segments encoding the variable part of light and heavy chains of an antibody (Ab) from the chromosomal DNA of hybridoma cells for the chimerization of Abs. A fundamental prerequisite for this is the knowledge of the exact sequences in the 5'-untranslated region of light and heavy chain mRNA, and of the joining segment used for rearrangement. This allows the design of nondegenerated oligodeoxyribonucleotides for PCR. The primer design permits directional cloning of the amplified, promoterless fragments into cassette vectors, in which they will be linked to the appropriate human constant domains and immunoglobulin (Ig) promoter/enhancer elements. The method is illustrated for chimerization of an Ab directed against the human T-lymphocyte antigen, CD4. The chimerized Ab is secreted in abundant quantities after transfection of the engineered plasmids into non-Ig-producing myeloma cells. PMID- 1937058 TI - Improving older women's health. PMID- 1937057 TI - Cloning and analysis of a gene encoding ovine interferon alpha-II. AB - A gene encoding ovine interferon alpha (IFN alpha) was identified from an ovine liver genomic library. Based on nucleotide and deduced amino acid sequencing analyses, this gene appears to code for an IFN of the alpha II family different from the ovine embryonic IFNs found to date. PMID- 1937059 TI - Behavioral problems associated with dementia: diagnosis and treatment. AB - The more common behavioral disturbances associated with dementia in elderly patients include depression, psychosis, and agitation. Diagnosis of the underlying cause of these behavioral disturbances begins with a careful investigation of possible medical or toxic disturbances, followed by a careful diagnostic assessment for co-morbid psychiatric syndromes. Treatment of the psychiatric syndromes is often beneficial to the demented patient, improving functional status and reducing the potential for additional morbidity. Patients receiving psychoactive drugs require close monitoring for side effects. PMID- 1937060 TI - Selecting routine outpatient tests for older patients. AB - In the routine management of elderly patients, the usual objective of diagnostic testing is to prevent the loss of independence when chronic disorders interfere with activities of daily living. Simple in-office tests and other outpatient procedures are the mainstay for diagnosing and monitoring dementia, incontinence, impairment of vision and hearing, alterations in nutrition, musculoskeletal disease, pulmonary and cardiovascular disease, malignancy, and endocrine disorders. In selecting diagnostic tests, physicians must weigh the alternatives based on patient needs, cost-effectiveness, and the availability of nearby medical services. PMID- 1937061 TI - An update on the use of drugs for common eye problems in older patients. AB - Common ophthalmic disorders occurring in older adults often can be managed in the primary care setting with appropriate medication. This review focuses on pharmacologic intervention for dry eye, allergy, glaucoma, inflammatory disease, and infection, as well as diagnostic agents for dilation. Discussed are the selection, proper administration, dosage forms, and side effects of ophthalmic agents. PMID- 1937062 TI - Therapies for symptomatic primary osteoporosis. AB - There is no universally accepted pharmacologic treatment for primary symptomatic osteoporosis. However, three agents discussed in this review show varying degrees of promise. Calcitonin increases bone density and has the added benefit of analgesic properties. Etidronate disodium, a diphosphonate approved for symptomatic Paget's disease, has been shown to increase bone density and decrease fractures in osteoporosis. Sodium fluoride, although an effective stimulator of bone growth in low turnover osteoporosis, has been associated with toxicity and increased fractures. PMID- 1937063 TI - Depression: treating a familiar enemy. PMID- 1937064 TI - Disturbance of learning and memory by the alkylation of muscarinic acetylcholine receptors by propylbenzilylcholine mustard. AB - The effects of blockade of muscarinic acetylcholine receptors (mAChR) in rat cerebral cortex on learning and memory were studied by the use of passive and active avoidance tests. Injection of propylbenzilylcholine mustard (PrBCM) into frontal, parietal and occipital cortex decreased mAChR dose dependently, as assessed by 3H-quinuclidinylbenzilate binding studies. Bilateral injection of PrBCM into frontal and/or parietal but not occipital cortex impaired passive avoidance learning. The results suggest that intact muscarinic neurotransmission is important for registration and recall, but not retention phases of the learning and memory process. Alkylation of mAChR by PrBCM also caused impairment in the performance of active avoidance task. PMID- 1937065 TI - Catecholamine and acetylcholine in the rat cerebral cortex with special reference to pathogenetic mechanisms of Alzheimer's disease. AB - A direct synapse between catecholamine fibers and neuropeptide Y-containing neurons is demonstrated in rat cerebral cortex using an immunohistochemical double-staining method under the electron microscope. A new method to produce a selective reduction in cholinergic neurons in the basal forebrain without damage to the non-cholinergic neurons, passing fibers or other cholinergic systems, is described. This animal model seems to be very useful to analyze the pathogenesis of Alzheimer's disease and to examine the function of cholinergic neurons of the basal forebrain. PMID- 1937066 TI - Expression of Alzheimer amyloid beta-protein precursor gene in neuronal cells. AB - Five forms of Alzheimer amyloid beta-protein precursors (APP or BPP) have been found. Among them, APP695 is predominantly found in neuronal cells and may be involved in some neuronal functions. In the present work, we investigated the relationship between the APP expression and the formation of neurites, a typical neuronal morphology, by measuring the amounts of three major APP mRNAs in PC12 cells, using the polymerase chain reaction. In PC12 cells, nerve growth factor which induced a neurite formation, enhanced the expression of APP695. The ratio of APP695 to APP770 increased 2.6-fold after 6 days of treatment. Cyclic AMP also induced a similar morphological change, but did not affect the APP expression pattern. Thus, the neuronal expression of the APP gene is not directly related with neurite formation. We have also identified cis-elements for the neuronal expression of APP gene. PMID- 1937067 TI - Calcium requirement in elderly Japanese women. AB - In order to evaluate calcium requirements (RC) in Japanese elderly women, a calcium balance study was carried out in 9 osteoporotics (73.9 +/- 2.7 years old, mean +/- SE) and 9 normal elderly women (67.0 +/- 2.5 years old). Diet containing 700 mg/day of calcium were given for at least 1 week. Then, diets containing approximately 700 mg/day (722.5 +/- 91.9 mg/day) of calcium in the 1st week and 1,474 mg/day of calcium in the 2nd week were served. The amount of calcium intake to maintain zero balance, defined as daily RC, was 550.4 +/- 50.0 and 648.8 +/- 44.7 mg/day in normal and osteoporotic subjects, respectively. There was no statistically significant difference between these two groups. Although the recommended daily allowance (RDA) for the adult Japanese is 600 mg/day, our study suggests that RDA in the elderly Japanese should be 847 mg. PMID- 1937068 TI - Receptor function of low-density lipoproteins in Werner's syndrome. AB - Abnormal lipoprotein metabolism and its cause were studied in 10 patients with Werner's syndrome. Seven of the 10 patients had hypercholesterolemia (greater than 250 mg dl-1). A significant positive correlation (p less than 0.01) was found between serum total cholesterol levels and LDL receptor activity. In monocyte-derived macrophages of patients with this syndrome, the uptake, lysosomal hydrolysis and re-esterification of free cholesterol are enhanced. This abnormal accumulation of cholesterol ester may cause accelerated conversion of macrophages to foam cells in Werner's syndrome. PMID- 1937069 TI - Role of serum amyloid P component for systemic amyloidosis in transgenic mice carrying human mutant transthyretin gene. AB - The role of serum amyloid P component (SAP) for systemic amyloidosis in a transgenic mouse model for an autosomal dominant disease, familial amyloidotic polyneuropathy (FAP), was examined. For this purpose, two lines of transgenic mouse were produced by introducing the human mutant transthyretin (TTR) gene and the human SAP gene, respectively. Two lines of transgenic mice were mated to produce double transgenic mice carrying both human mutant TTR gene and human SAP gene. The serum concentration of human SAP in these transgenic mice was about 42 micrograms/ml and was about equal to that in human control serum. In case of single transgenic mice carrying human mutant TTR gene, amyloid deposition starts at around 6 months of age, and the amount of amyloid deposition increases gradually with age. Amyloid deposition is observed in many tissues including heart, kidney and thyroid gland, where amyloid deposition is commonly observed in FAP patients. In double transgenic mice, onset, progression and tissue distribution of amyloid deposition were the same as those in single transgenic mouse. These results clearly suggest that SAP is not important for the initiation and progression of amyloid deposition. PMID- 1937070 TI - PERG and spectral sensitivity in ocular hypertensive and chronic open-angle glaucoma patients. AB - Pattern electroretrinography (PERG) was performed in 33 patients with chronic open-angle glaucoma (COAG), 18 ocular hypertensive (OH) patients, and 24 normal subjects. COAG patients exhibited significantly lower PERG amplitudes than did normal subjects (P8rps = 0.025; P16rps less than 0.0001). The OH patients fell into two distinct groups: those with normal PERG scores and those with lower than normal scores. OH patients with PERG scores significantly lower than control values demonstrated significantly larger cup-to-disc ratios (P = 0.002) and higher initial intraocular pressures (IOPs) than did OH patients with normal PERG scores (P = 0.021). In the 11 OH patients in whom spectral sensitivity measurement was available, statistically significant correlations were found between the blue-cone sensitivity loss and the PERG amplitude (r8rps = 0.772, P8rps = 0.0053 and r16rps = 0.699, P16rps = 0.0167, respectively. Our results demonstrate reduced PERG amplitude in high-risk OH patients and further illustrate the correlation between PERG amplitude and blue-cone spectral sensitivity in OH subjects. Confirmation of the roles of PERG and spectral sensitivity in the detection of early glaucoma requires longitudinal study. PMID- 1937071 TI - Fundus changes in membranoproliferative glomerulonephritis type II. A fluorescein angiographic study of 23 patients. AB - A total of 23 patients aged between 11 and 64 years who had biopsy-proven membranoproliferative glomerulonephritis type II (dense deposit disease) were studied using fluorescein angiography of the retina. With the exception of two adolescents, all patients exhibited small subretinal nodules that were similar to basal laminar drusen. Subjects with a long history of renal disease displayed more numerous and larger nodules as well as atrophic changes. Four subjects presented with subretinal neovascular membranes. PMID- 1937072 TI - Effects of prostaglandin D2 and its analogue, BW245C, on intraocular pressure in humans. AB - The effects of topically applied prostaglandin (PG) D2 and BW245C, a potent PGD2 agonist, on intraocular pressure (IOP) were studied in normotensive human volunteers. Doses of 5 and 10 micrograms PGD2 induced a mean reduction in IOP of 0.8 and 1 mmHg, respectively. At a dose of 50 micrograms, hypotension was preceded by initial hypertension (4 mmHg at 0.5 h) and the magnitude of the mean IOP reduction during the hypotensive phase was 1.1 mmHg. The application of BW245C (2.5 micrograms) induced an IOP change similar to that observed following treatment with 50 micrograms PGD2. Side effects caused by these compounds included conjunctival hyperemia, itching, and foreign-body and mild burning sensations. However, miosis and signs of intraocular inflammation were not observed. These results indicate that although PGD2 and BW245C are effective in reducing human IOP, their clinical usefulness as anti-glaucoma drugs may be limited by the extraocular side effects. PMID- 1937073 TI - Evaluation of electrofunctional data following argon-laser trabeculoplasty in primary open-angle glaucoma. AB - To establish whether or not glaucomatous damage is reversible, we obtained pattern-reversal electroretinograms (PERGs) and visual evoked potentials (VEPs) in 25 eyes of 25 patients suffering from bilateral primary open-angle glaucoma (POAG) before and after argon-laser trabeculoplasty. The laser treatment was carried out in only one eye chosen at random, and the fellow eye was used as a control. In the present study we intended to verify the possibility of using electrofunctional techniques to determine the two distinct and, probably, consecutive glaucomatous alterations occurring in ganglion cells: functional (reversible) and anatomical (irreversible). The results obtained indicate that glaucomatous damage is irreversible. We propose that such alterations differ very slightly and that the current electrofunctional techniques may not be sufficiently sophisticated to distinguish between them. PMID- 1937074 TI - A multiport illumination system for panoramic bi-manual vitreous surgery. AB - A multiport illumination system (MIS) suitable for use during microsurgery of the vitreous body is presented. The MIS consists of several thin, illuminated pilot tubes, which are secured in the pars plana region and emit bright light at a wide angle. Through their lumen interchangeable 20 gauge instruments for active bi manual vitreous surgery and an infusion pipe can be introduced. The system illuminates the entire field of wide-angle observation devices without the need for an additional hand-held light source. PMID- 1937075 TI - Motion perception in the peripheral visual field. AB - Thresholds were determined for the perception of the motion of a single bar moving at different positions in the field of view. Performance in the temporal hemified was slightly superior to that in the nasal hemifield and depended on the orientation as well as on the direction of the motion. The perception of horizontal motion was better than that of vertical motion. In spite of large variations, centrifugal motion was significantly more readily perceived than centripetal motion. PMID- 1937076 TI - Influence of missed catch trials on the visual field in normal subjects. AB - A total of 20 healthy individuals purposely missed an increasing number of individual catch trial questions (false positive or negative errors or fixation losses) when tested on the Humphrey Field Analyzer to determine the effect on the normal visual field. As determined by Statpac, the global indices and probability maps became significantly altered from those for the control fields at a prevalence of 20% for false negatives and 33% for fixation losses and false positives. However, the perimeter's recorded prevalence of missed catch trials showed a wide distribution from the percentage purposely missed. A high prevalence of missed catch trials was also indicated by a greater than normal mean defect and number of questions asked. This study suggests that although the number of missed catch trials are often recorded inaccurately, they help to identify unreliable normal visual fields, as do the mean defect and the number of questions asked. PMID- 1937077 TI - Blood-retina barrier permeability and its relation to the progression of diabetic retinopathy in type 1 diabetics. An 8-year follow-up study. AB - Blood-retina barrier (BRB) permeability and its relation to the progression of diabetic retinopathy was studied over an 8-year period in 50 insulin-dependent diabetic patients. Initially, the patients underwent an ophthalmological examination, including measurement of best corrected visual acuity, fundus photography and vitreous fluorometry for determination of BRB permeability. After 8 years the patients were reexamined and their retinal status and clinical course were evaluated. We found a positive correlation between a high initial permeability value and an unfavorable clinical course using the parameter photocoagulation. A decrease in follow-up visual acuity was also associated with high initial permeability; however, this correlation was not statistically significant. A significant difference in mean blood pressure was found between values measured in laser-treated patients vs a group that did not undergo such therapy. Thus, in patients showing the same initial retinal morphology, high permeability seems to indicate an unfavorable disease course. The extent to which BRB permeability can be a valuable supplement to fluorescein angiography and three-mirror examination in the clinical decision process needs to be further evaluated. PMID- 1937078 TI - Elevated prolactin levels in human aqueous humor of patients with anterior uveitis. AB - Evidence is accumulating that prolactin (PRL) may play a physiological role in the regulation of humoral and cell-mediated immune responses. On the basis of these observations, we measured levels in the serum and aqueous humor of 28 patients with cataract or anterior uveitis with concomitant cataract. Intraocular concentrations were measured in a range from 0.1 to 3.4 ng/ml. Whereas serum PRL levels failed to show significant differences between the two groups (P = 0.39), intraocular concentrations were significantly higher in uveitis patients (P less than 0.001). The level in aqueous humor did not reflect the serum concentration in either group. To the best of our knowledge, this is the first study measuring PRL concentrations in human aqueous humor. PMID- 1937079 TI - Breakdown of the blood-retinal barrier in S-antigen-induced uveoretinitis in rats. AB - Experimental autoimmune uveoretinitis was induced in Lewis rats by footpad injection of purified, bovine retinal soluble antigen (S-antigen) with complete Freund's adjuvant. Control animals received adjuvant only. At the peak of ocular inflammation the animals received an intravenous injection of the tracer horseradish peroxidase, and the eyes were removed and processed for peroxidase cytochemistry. A breakdown of the blood-retinal barrier occurred at the level of the retinal venules. Peroxidase reaction product was demonstrable in the interendothelial tight junctions and in the perivascular spaces. Heavy infiltration of inflammatory cells was also found in and around the venular wall. The endothelial cells of venules and capillaries were hypertrophied and showed swollen endoplasmic reticulum and Golgi apparatus as well as increased numbers of ribosomes and cytoplasmic fibrils; pericytes and smooth-muscle cells showed a similar synthetic phenotype and the basal lamina of these cells was thickened. PMID- 1937080 TI - Daunorubicin treatment in a refined experimental model of proliferative vitreoretinopathy. AB - A condition similar to proliferative vitreoretinopathy (PVR) in man can be produced by injecting 25,000 homologous dermal fibroblasts into rabbit eyes following gas compression of the vitreous. Daunorubicin (15 nmol) was effective in preventing retinal detachment in this model when injected simultaneously with the fibroblasts or in two doses (10 nmol followed by 5 nmol 4 h later) on the 3rd day after fibroblast injection. A single dose of 15 nmol on the 3rd day was not effective in preventing retinal detachment. These results suggest that daunorubicin may be clinically useful in preventing PVR when given by injection both at the time of vitrectomy as well as later, when protein exudation and pigment clumps in the vitreous cavity herald the onset of PVR. PMID- 1937081 TI - Vitreous replacement by gas as a therapeutic modality in bacterial endophthalmitis. AB - We investigated vitreous replacement by long-lasting gas in the management of severe Staphylococcus aureus endophthalmitis in 19 rabbits randomized for vitrectomy (9 animals) and for vitrectomy followed by replacement of the vitreous by a 20% perfluoropropane-80% air mixture (10 animals). Both groups received systemic antibiotics and achieved comparable intraocular antibiotic levels. Clinically and histopathologically, gas-filled eyes demonstrated less inflammation than did eyes without gas (P less than 0.01). Replacement of vitreous by gas offers an effective adjunct to vitrectomy by eliminating a culture medium, preventing vitreous abscess formation, enabling fundus visualization, and delaying the onset of retinal detachment. PMID- 1937082 TI - In vivo observations on experimental corneal neovascularization with a newly developed macroscope. AB - The process of corneal neovascularization induced by alkali burns was periodically observed with a newly developed macroscope. The central corneas were burned using filter discs measuring 6 mm in diameter that had been immersed in 1 N NaOH. At 0, 1, 3 and 7 days and at 2, 3 and 4 weeks after injury, the corneas were observed with the macroscope and then examined histologically. At 1 day post burn, the limbal vascular plexus was engorged but no new vessel formation was detected. By 3 days, many vascular sprouts had arisen from the limbal vascular arcade. At 7 days, the vascular sprouts grew and became fine new vessels. At 2 weeks, the new vessels lengthened further to the central cornea. At 3 weeks, trunk vessels extended and branched like a vascular tree. Blood in the trunk vessels appeared to flow slowly to and fro. The ends of the vessels swelled in a fusiform shape on the application of slight pressure of the macroscope probe. Histological examination revealed that the ends of the vessels consisted of single vascular endothelial cells and the trunk vessels were covered by pericytes. By 4 weeks, the branch vessels around the burned lesion had degenerated and collapsed. Thus, our in vivo study using the new macroscope not only clarified the process of corneal neovascularization from the early to the regressive phases but also provided some valuable new information. PMID- 1937083 TI - Histopathology studies in human malignant melanomas of the choroid after unsuccessful treatment with 106Ru/106Rh ophthalmic applicators. AB - Choroidal malignant melanomas were examined after unsuccessful brachytherapy with 106Ru/106Rh ophthalmic plaques. The histologic findings were compared with those obtained in non-irradiated melanomas similar in size and location. Both groups revealed no significant clinical difference apart from the lower average age of the irradiated patients. Some of the histologic features (scar formation, changes in the distribution of cell types, rate of mitosis) represented reactions to irradiation. No single histologic feature was strongly correlated to the irradiated group. The phenomenon of radioinsensitivity observed in some malignant melanomas cannot be fully elucidated using conventional histologic methods. PMID- 1937084 TI - Follow-up study of X-linked retinoschisis. PMID- 1937085 TI - Lectin binding to human corneal endothelium. PMID- 1937086 TI - Hypopyon in bacterial keratitis. PMID- 1937087 TI - [Effect of air pollution on the reproductive function of women]. PMID- 1937088 TI - [Evaluation of the limits for permissible grain dust concentration in the air]. PMID- 1937089 TI - [Hygienic aspects of the hot water supply]. AB - Hygienic significance of hot water-supply was demonstrated. In the case of the sanitary inspection deficiency it may be the complaints appearance. Hygiene of hot water-supply seems as an independent scientific branch of hygiene. PMID- 1937090 TI - [Hygienic importance of the combined actions of pesticides and surface-active agents (survey)]. PMID- 1937091 TI - [Hygienic effectiveness of the improvement of sanitary conditions in agglomeration mills of the ferrous metal industry]. PMID- 1937092 TI - [Comparative evaluation of the dust's fibrinogen activity in asbestos-forming units production]. PMID- 1937093 TI - [Immune status under the action of forage dust]. PMID- 1937094 TI - [The role of molds and dusts in respiratory tract diseases of construction workers]. AB - Silicosis harmful dust produced into the air of working zone during thorough repair of dwelling houses may traumatize the mucous coat of respiratory tract. Simultaneously mould fungi propaguls get into air. Occupational diseases (dust bronchitis) development caused by this dust during capital repair is substituted. It was expressed in the bronchopulmonary pathology with positive reaction of fungi antigen precipitation and detection of the fungi in pathological substances of patients. PMID- 1937095 TI - [Methodical approaches to the sanitary inspection of field-camps]. PMID- 1937096 TI - [Sanitary bacteriological study of half-smoked fish sausages]. PMID- 1937097 TI - [Changes in the physical development of preschool- and elementary-school-age children in Moscow during the last twenty years]. AB - Analysis of the 4-10-aged children habitus (above 8,000 persons) in Moscow from 60-th to nowadays shows the growth acceleration from middle 60th to 70th, and then, from 80th to nowadays, significant decreasing of growth parameters. PMID- 1937098 TI - [Some features of thermoregulation in young girls in the process of professional adaptation to electro-technical professions]. AB - Thermoregulation of 15-16 aged young girls (76 persons) studying electrotechnical professions was investigated. Spring strain of thermoregulation was noted. This data may be used in the professional adaptation and hygienic standardization of educational process. PMID- 1937099 TI - [Effect of prophylactic ultraviolet treatments on the immune system of animals with experimental myocarditis]. PMID- 1937100 TI - [Behavioral effects of the combined chronic action of 9375 and 1765 MHz microwaves]. AB - Combined pulse-discrete microwave irradiation (9375 and 1765 MHz, irradiance flux density to 375 microW/cm2, by 12 h/day for 4 months) caused faint inhibition of CNS in locomotion activity and defensive reflex parameters. PMID- 1937101 TI - [Determination of sterols in air by thin-layer chromatography in sanitary chemical studies of polymeric compounds]. PMID- 1937102 TI - [Work-related and physiologic problems in working with computers and video terminals]. PMID- 1937104 TI - [Effects of pesticides on the natural cytotoxicity of murine spleen cells in relation to the animals' age]. PMID- 1937103 TI - [Experimental model for the study of allergic sensitization to vitamins in the mother-baby system]. AB - Vitamins are mostly used in pregnancy time. In this time the vitamin allergy of 2.1% expectant mothers was noted. 3 pathways of the vitamin allergic sensibilization transmission from mother to baby was estimated using biophysical termistographic method. It has great importance for the allergic disease prophylaxis. PMID- 1937105 TI - [Sensitizing effects of fodder yeast dust]. AB - Sensibilization activity of the fodder yeasts grown on the sulphate wastes of pulp and paper mills in inhalation, into and onto skin injection experiments with guinea pigs was studied. This activity depended on the action intensity. Application onto skin is more effective, than injection into skin. 10 mg/m3 caused statistically significant allergic effects in inhalation experiments, but 0.8 mg/m3--had no significant effects. PMID- 1937106 TI - [Evaluation of the biological significance of changes in the organism under external influence]. AB - Estimation of the statistical reliability and the biological significance of changes caused by external actions are two independent parts of data analysis. Statistical reliability is a criterion of the reality. The principal unhealthy effects are decreasing of living term and increasing of morbidity. Other effects seem harmful on the basis of physiological analysis, and those are less reliable. Increasing of harmful effects frequency, but not the parameters values changes (if opposite is not proved), is a criterion of unhealthy effects. PMID- 1937107 TI - [Solubility in water and skin absorptive toxicity of pesticides]. AB - One parameter equation connected skin-resorptive toxicity of pesticides and its solubility in water was maintained. For defoliants, insecticides, acaricides, nematocides and zoocides a good correlation between calculated and experimental values of skin-resorptive toxicity for rats was shown. PMID- 1937108 TI - [Changes in human liver microsomal oxidation under impulse aerodynamic effects]. PMID- 1937109 TI - [Significance of sublethal injuries in microorganisms (review)]. PMID- 1937110 TI - [Ceruloplasmin changes in blood serum in response to various factors (review)]. PMID- 1937111 TI - [Centralization of management and financing of sanitary epidemic services]. PMID- 1937112 TI - [Work experience of a sanitary epidemic station in the environmental hygiene of an industrial city]. PMID- 1937113 TI - [Hygienic aspects of establishing a healthy life style in preschool children]. PMID- 1937114 TI - [Probability approach to the functional description of dose-time-effect relationships]. PMID- 1937115 TI - [Comparative reliability of methods for toxicity prediction in validating the approximate acceptable level of N,N,N',N'-tetramethylethylenediamine in reservoir water]. PMID- 1937116 TI - [Methods for detecting copper, zinc, lead and tin in food products]. PMID- 1937117 TI - [Methods of studying the health status of the population in industrial regions including remote effects]. PMID- 1937119 TI - [Systems approach to the sanitary-hygienic and anti-epidemic service of the population]. PMID- 1937118 TI - [Assessment of health status by screening methods]. PMID- 1937120 TI - [Radical hysterectomy with pelvic lymphadenectomy for the treatment of invasive IB and IIA cervical cancer: review of 153 cases]. AB - One hundred and fifty three patients with carcinoma of the cervix, stages IB and IIA, were treated with radical hysterectomy and pelvic lymphadenectomy, during the period from October 1978 to December, 1989; 85.6% were at stages IB and 14.4% at IIA. The most frequent histological type was the epidermoid one in 91.5%. Average age was 48 years; 94 patients out of 107 (87.8%) were followed up during five years at least. Total survival at five years, was 75.7%; with positive lymphatic nodes, 50% and with negative nodes, 77.2%. In 17.6% of the cases post operative radiotherapy was required. Late morbidity was most frequent as vesical dysfunction (17.6%); there were vesicovaginal fistulae (1.3%); and operative mortality was 0.6%). The present study confirms that this type of surgery is justified, as to survival and morbi-mortality, and it allows a histopathological evaluation that shows risk factors, as to recurrence. PMID- 1937121 TI - [Erythema nodosum and pregnancy. Report of a case]. AB - Erythema nodosum is a rare disease, it appears frequently in association with infectious disease and with some drugs administration. A case associated with pregnancy is presented. The importance of hormonal behavior in its genesis, is considered. We conclude that the transitional hormone state in women is a very important factor in it's appearance. Estrogens play an important roll in the immunological response. PMID- 1937122 TI - [Polycythemia in the newborn. III: blood volume in asphyxia and meconium]. AB - Several authors had reported high blood volumes (BV) and Low placental residual blood volumes (PRBV) in hypoxic human newborns, and also in asphyxiated experimentally animals. Those findings could be explained by and exaggerated intrauterine placental transfusion, ante or intrapartum. The authors had observed high cord blood and 24-48 hs. hematocrits in meconium-stained amniotic fluid (MSAF) and/or low 1 minute Apgar score newborns (Nb), despite early cord clamping. Sometimes, by delaying cord clamping up to 1 minute, those hematocrits had a tendency to decrease, instead of increasing. In view of that, it was decided to measure BV in a small group of similar type of Nb's with Evans blue (T 1824) and to practice in some of them a delayed cord clamping, but elevating the infant above the introitus (DECC). The BV values obtained were a little higher than the ones from the literature, being the most elevated in Nb's with MSAF and the lowest from cesarean. Also, the early cord clamping babies had higher BV than the DECC. All the MSAF Nb's had low plasmatic BV. BV was positively related to Birth Weight and the Hematocrit, and inversely to the Apgar score and the cord blood pH. Unexpectedly, delayed cord clamping was only slightly related to Red Cell BV, not to BV. MSAF constitutes 10% of all deliveries and delayed cord clamping has to be re-evaluated, because it offers a good chance for those babies of developing a normal BV or Hct's. PMID- 1937123 TI - [Pharmacologic management of dysfunctional uterine hemorrhage]. AB - From April 1st. to November 15, 1989, 38 patients with disfunctional uterine bleeding, were managed with a combination of ethinylestradiol-norethindrone (0.035 + 0.5mg) for both hemostasis and control. Endometrial sampling with Novak's canula was obtained, and the patient were followed during three months. The mean age was 27 +/- 5.6 years. The mean bleeding time before diagnosis was 12.8 days. The pathologic findings showed a representative distribution of disfunctional disorder. 89.4% of the patients had a good response, with confidence intervals between 81-97%. These findings support hormonal therapy as first alternative in women younger then 35 years old with disfunctional uterine bleeding. PMID- 1937124 TI - [Teratologic effects of benzodiazepines]. AB - Benzodiazepines are drugs that belong to the group of minor tranquilizers. They derive from the 1-4, benzodiazepine common nucleus that was obtained by chemical synthesis and act upon the GABA receptors increasing their affinity, thus providing them with their tranquilizing, miorelaxing, and anticonvulsant properties. Due to these characteristics they have been used in a wide variety of disorders accompanied by anxiety, hyperexitability, convulsions, and muscular hypertony, as well as during pregnancy and labor. Before using them in pregnant women, the physician should consider the conditions of the product "in uterus" since, according to experimental evidences, benzodiazepines could interfere with embryonary development, mainly with those involved in central nervous system mechanisms causing tissular alterations, retardment in cellular differentiation, and behavioral disturbances. Besides, since the fetus has lower excretion rate than that of the mother, drug concentrations are greater than the therapeutic ones and fetal tolerance to the compound, administered during the last trimester, is reduced, originating abstinence or intoxication syndromes in the newborn. It is concluded that more research is needed to evaluate all the aftereffects caused by using these drugs during pregnancy. PMID- 1937125 TI - [Treatment of the hyperprolactinemic states with lisuride in a simple open study]. AB - A simple open study was undertaken in order to assess the value of the dopamine agonist lisuride in the treatment of patients with two types of hyperprolactinemia: Six patients with pituitary adenoma and two with "idiopathic hyperprolactinemia". All patients were started on a dose of 0.2 mg per os per day until values of serum prolactin became normal (two to eleven months in the first group), except for two that required increment to 0.4 mg/day after the first four months without effect; both responded satisfactorily to the increased dose. Side effects were mild nausea end occasional vomiting, except in one case of the first group, which abandoned the treatment due to intense vomiting. One of the patients of "idiopathic hyperprolactinemia" required the dose to be increased to 0.4 mg/day after the first four months and finally responded after two more months with the higher dose. The second patient of this group did not respond even to a dose of 1 mg/day, which was otherwise well tolerated. PMID- 1937126 TI - Therapeutic potential of vitamin E in the pathogenesis of spontaneous atherosclerosis. AB - Spontaneous atherosclerosis is largely an occlusive disease of medium-size arteries whose progression in a hyperlipidemic environment reflects chronic interactions among injury stimuli to the vessel wall and "responses to injury" by vascular tissue and certain blood components. Development of vessel lesions in animal models of spontaneous atherosclerosis and (at least in principle) in man largely reflects responses of three major cell types (vascular endothelial cells, vascular smooth muscle cells, monocytes-macrophages) as well as the content and distribution of lipids among various lipoprotein subclasses and the increased atherogenicity of modified (e.g., oxidized) lipoproteins. The severe clinical complications associated with spontaneous atherosclerosis, along with its rather common incidence in man, have focused attention on the prevention and therapy of this vascular disease state. Some pharmacological studies in animal models of spontaneous atherosclerosis and some retrospective epidemiological studies in man suggest that vitamin E, the principal (if not sole) lipid-soluble chain-breaking tissue antioxidant, might have therapeutic benefit as an antiatherosclerotic agent. This suggestion gains support from a variety of compelling in vitro evidence demonstrating direct influences of vitamin E on cells and lipoproteins likely involved in the pathogenesis of spontaneous atherosclerosis. Biochemical and cellular data indicate that the potential antiatherogenic activity of vitamin E could reflect its activities as a regulator of endothelial, smooth muscle, or monocyte-macrophage function, an inhibitor of endothelial membrane lipid peroxidation, a modulator of plasma lipid levels and lipid distribution among circulating lipoproteins, and a preventor of lipoprotein oxidative modification. On the other hand, there is a comparative lack of conclusive evidence from animal models regarding: (a) the importance to atherogenesis of vascular and cellular processes modulated by vitamin E; (b) the influence of vitamin E on these processes in vivo and, consequently, on the initiation/progression of spontaneous atherosclerosis. Therefore, pharmacologic investigation of vitamin E (and synthetic, vitamin E-like antioxidants) in nutritional and hyperlipidemic animal models of spontaneous atherosclerosis is required to establish whether any atherosclerotic impact is associated with vitamin E and, if so, what the mechanistic basis of the therapeutic benefit is. Such a line of experimental inquiry should also increase our understanding of the pathogenesis of atherosclerotic vessel disease per se. PMID- 1937127 TI - The use of diphenylene iodonium and its analogues to investigate the role of the NADPH oxidase in the tumoricidal activity of macrophages in vitro. AB - Lipopolysaccharide (LPS) was shown to induce tumoricidal activity in peritoneal macrophages. The optimal concentration was found to be 25 micrograms/mL. Approximately 20-h exposure to LPS was required before maximal tumor cell killing was attained. Optimal tumor killing was obtained with a ratio of tumor cell to macrophages of 1:40 with the macrophages in a confluent layer. Diphenylene iodonium (DPI) reduced the tumor cell killing in a dose dependent manner up to 1 microM. Under similar conditions DPI was shown to inhibit the superoxide production of macrophages and this supports the view that the production of oxygen radicals is important in the killing of tumor cells by macrophages and that the inhibitor DPI can be used to investigate their contribution to cytotoxicity. PMID- 1937128 TI - Aldehydes, hydrogen peroxide, and organic radicals as mediators of ozone toxicity. AB - It is generally agreed that unsaturated fatty acids (UFA) are an important class of target molecule for reaction with ozone when polluted air is inhaled. Most discussions have implicated the UFA in cell membranes, but lung lining fluids also contain fatty acids that are from 20 to 40% unsaturated. Since UFA in lung lining fluids exist in a highly aquated environment, ozonation would be expected to produce aldehydes and hydrogen peroxide, rather than the Criegee ozonide. In agreement with this expectation, we find that ozonations of emulsions of fatty acids containing from one to four double bonds give one mole of H2O2 for each mole of ozone reacted. Ozonation of oleic acid emulsions and dioleoyl phosphatidyl choline gives similar results. with two moles of aldehydes and one mole of H2O2 formed per mole of ozone reacted. The net reaction that occurs when ozone reacts with pulmonary lipids is suggested to be given by equation 1. [formula: see text]. From 5 to 10% yields of Criegee ozonides also appear to be formed. In addition, a direct reaction of unknown mechanism occurs between ozone and UFA in homogeneous organic solution, in homogeneous solutions in water, in aqueous emulsions, and in lipid bilayers to give organic radicals that can be spin trapped. These radicals are suggested to be responsible for initiating lipid peroxidation of polyunsaturated fatty acids. Thus, aldehydes, hydrogen peroxide, and directly produced organic radicals are suggested to be mediators of ozone induced pathology. PMID- 1937129 TI - Another cholesterol hypothesis: cholesterol as antioxidant. AB - Current emphasis on cholesterol as agency if not cause of human atherosclerosis and subsequent cardiovascular disease ignores the essentiality of cholesterol in life processes. Additionally ignored is the ubiquitous presence of low levels of oxidized cholesterol derivatives (oxysterols) in human blood and select tissues, oxysterols also implicated in atherosclerosis. Whereas such oxysterols may be regarded putatively as agents injurious to the aorta, an alternative view of some of them is here proposed: that B-ring oxidized oxysterols of human blood represent past interception of blood and tissue oxidants in vivo by cholesterol as an ordinary aspect of oxygen metabolism. Such interception and subsequent efficient hepatic metabolism of oxysterols so formed, with biliary secretion and fecal excretion, constitute as in vivo antioxidant system. Whether cholesterol, oxysterols, oxidized lipoproteins, or oxidants in blood, singly or in concert, cause or exacerbate human atherosclerosis remains to be understood. PMID- 1937130 TI - Contradictory effects of superoxide dismutase after global or regional ischemia in the isolated rat heart. AB - The effect of superoxide dismutase was investigated in two different models of ischemia and reperfusion in the isolated rat heart: global and regional ischemia. The results of this comparison show that reperfusion arrhythmias after 10 and 15 min of regional ischemia, induced by occlusion of the left coronary artery, can be prevented by SOD confirming the results of other investigators. Paradoxically SOD was without effect after 10 min of global ischemia, obtained by stopping coronary flow completely. After 15 min of global ischemia, SOD induced ventricle fibrillation. Apparently the effect of SOD depends on the model of ischemia and reperfusion that is used. PMID- 1937131 TI - Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. AB - Lipid peroxidation often occurs in response to oxidative stress, and a great diversity of aldehydes are formed when lipid hydroperoxides break down in biological systems. Some of these aldehydes are highly reactive and may be considered as second toxic messengers which disseminate and augment initial free radical events. The aldehydes most intensively studied so far are 4 hydroxynonenal, 4-hydroxyhexenal, and malonaldehyde. The purpose of this review is to provide a comprehensive summary on the chemical properties of these aldehydes, the mechanisms of their formation and their occurrence in biological systems and methods for their determination. We will also review the reactions of 4-hydroxyalkenals and malonaldehyde with biomolecules (amino acids, proteins, nucleic acid bases), their metabolism in isolated cells and excretion in whole animals, as well as the many types of biological activities described so far, including cytotoxicity, genotoxicity, chemotactic activity, and effects on cell proliferation and gene expression. Structurally related compounds, such as acrolein, crotonaldehyde, and other 2-alkenals are also briefly discussed, since they have some properties in common with 4-hydroxyalkenals. PMID- 1937132 TI - Inverse correlation between resistance towards copper and towards the redox cycling compound paraquat: a study in copper-tolerant hepatocytes in tissue culture. AB - The essential mediatory role of copper or iron in the manifestation of paraquat toxicity has been demonstrated (Kohen and Chevion (1985) Free Rad. Res. Commun. 1, 79-88; Korbashi, P. et al. (1986) J. Biol. Chem. 261, 12472-12476). Several liver cell lines, characterized by their resistance to copper, were challenged with paraquat and their cross-resistance to paraquat and copper was studied. Cell growth and survival data showed that copper-resistant cells, containing elevated copper, are more sensitive towards paraquat than wild type cells. Copper-deprived resistant cells did not have this sensitivity. Paraquat was also shown to cause a marked degradation of cellular glutathione in all cell lines. Albeit the fact that the basal glutathione levels are higher in copper-resistant than in wild type cells, there is more paraquat-induced degradation of cellular glutathione (GSH + GSSG) in resistant cells. It is suggested that in copper-resistant cells which contain elevated levels of copper, paraquat-induced cellular injury is potentiated even where glutathione levels are elevated. Additionally, in vitro experiments are presented that support the in vivo findings demonstrating a role for copper in glutathione degradation. PMID- 1937133 TI - The reduction of ferrate(VI) to ferrate(V) by ascorbate. AB - The reduction of ferrate(VI) by ascorbate has been studied under anaerobic conditions in the pH range between 6.8 and 11.5 at 24 degrees C. A mechanism is proposed that is consistent with the observed rate constants k11 (HFeO4- + AH-) = (5.6 +/- 0.6) x 10(6) M-1 s-1, k12(FeO4(2-) + AH-) = (1.3 +/- 0.1) x 10(6) M-1 s 1 and the pK(HFeO4- in equilibrium with H(+) + FeO4(2-) = 7.9. Stoichiometric studies show that at high ratios of [AH-]/[FeO4(2-)], one ferrate(VI) oxidizes three molecules of ascorbate to the corresponding ascorbyl (A-) radicals. PMID- 1937134 TI - Free radical damage to proteins: the influence of the relative localization of radical generation, antioxidants, and target proteins. AB - Free radicals were generated at known rates in the aqueous phase (by means of 2,2'-azobis (2-amidinopropane) dihydrochloride [AAPH]) and in a membranous (lipid) phase (by means of 2,2'-azobis (2,4-dimethylvaleronitrile [AMVN]). A soluble protein (bovine serum albumin: BSA), and membranes of lysed mitochondria containing radioactively labeled monoamine oxidase (MAO), were exposed to the resultant radical fluxes. Antioxidants were added to the system, either in the aqueous phase (Trolox) or in a liposomal membrane phase (alpha-tocopherol). Protein damage was assessed as tryptophan oxidation and conformational changes in tryptophan fluorescence of the soluble protein, BSA, and as fragmentation of both BSA and monoamine oxidase. Radicals generated in the aqueous phase, by AAPH, were effective in damaging BSA and MAO. Radicals generated within the liposome membrane phase (by AMVN) were less effective against BSA than those deriving from AAPH. Liposomal AMVN radicals could damage MAO, present in a separate membranous phase, though again, less effectively than could AAPH-derived radicals. BSA could be protected by Trolox, the aqueous soluble antioxidant, but hardly by tocopherol itself. Damage to MAO was limited by Trolox, and also by the hydrophobic antioxidant, tocopherol. Damaging reactions due to radicals generated in a membrane phase were significantly accelerated when the membrane was peroxidizable (soybean phosphatidylcholine) rather than nonperoxidizable (saturated dimyristoyl phosphatidylcholine). Thus lipid radicals also played some role in protein damage in these systems. BSA was attacked similarly in the presence or absence of liposomes by AAPH. Correspondingly, BSA could inhibit the peroxidation of liposomes induced by AAPH and less efficiently that induced by AMVN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937135 TI - Electromechanical effects of menadione on isolated rat heart in relation to oxidative stress. AB - Although Ca2+ overloading has been observed in hepatocytes and in the isolated liver treated with 0.2 mM menadione, it has not been determined if menadione has similar effects on cardiac tissue and, if so, whether Ca2+ overloading leads to cardiac contracture, and if such an event results from plasma membrane peroxidation initiated by oxidative stress. The present study reveals that when the isolated heart is perfused with 0.2 mM menadione for 30 min, it shows Ca2+ overloading, which can not be reversed even after 30 min of drug-free perfusion. The time courses of glutathione, ethane, and LDH release from the hearts do not show a parallel pattern of abnormality between 30 and 60 min, indicating that contractile failure precedes the development of lipid peroxidation or plasma membrane disintegration. The evidence that the plasma membrane of menadione treated rat cardiac tissue remains intact is supported by the observation that the resting membrane potential of the atrium remains virtually unchanged during the 30 min of drug exposure and then gradually falls (-67 +/- 3.1 vs. -76 +/- 2 mv) only during the last 10 min of the drug washout. Interestingly, even after the atria are treated with menadione for 30 min and followed by washout of 30 min, and have shown calcium overloading, as evidenced by contracture, they are still capable of generating action potentials in response to electrical field stimulation. PMID- 1937136 TI - Effects of hypoxia and reoxygenation on the conversion of xanthine dehydrogenase to oxidase in Chinese hamster V79 cells. AB - The effects of hypoxia and reoxygenation on the conversion of xanthine dehydrogenase to the free radical-producing xanthine oxidase in Chinese hamster V79 cells have been investigated using a newly developed fluorimetric enzyme assay. Hypoxia caused an increase in xanthine oxidase activity from 25% to 80% of the total activity of xanthine oxidase and dehydrogenase. The ratio returned to normal levels within 24 h of aerobic incubation. Hypoxia caused the release of xanthine oxidase in the medium of V79 cells and an increase in total protein concentration in the medium. There was an early change induced in lipid peroxidation markers and this was inhibited by allopurinol. The effects of glucose deprivation and calcium blockers were also investigated. Fura-2 AM was found to interact with V79 cells, making it impossible to determine intracellular calcium levels in V79 cells by this reagent. PMID- 1937137 TI - Enhanced electron transfer by GTP: cross-membrane electron signaling by G proteins? AB - Activation of several receptor types is followed by their binding to a G-protein. Prior to transmission of the agonist signal, the G-protein which had affinity for guanosine 5-diphosphate (GDP) binds guanosine 5-triphosphate (GTP) instead. Because evidence exists that several agonist groups activate their receptors by reduction, we evaluated whether the nucleotide associated with G-proteins could enhance electron flow. Using a model system of ferrous iron and ferric cytochrome c, it was determined that substitution of GTP for GDP led to an enhanced reduction of ferric cytochrome c. These results support the concept that cellular activation by certain receptors may involve reductive activation with the participation of GTP and G-proteins. We speculate that GTP, when bound to G protein, can facilitate electron transfer perhaps from the receptor or the G protein to the catalytic subunit of the adenylate cyclase enzyme. PMID- 1937138 TI - Propranolol preserves ultrastructure in adult cardiocytes exposed to anoxia/reoxygenation: a morphometric analysis. AB - The protective effect of d,l-propranolol was studied using freshly isolated canine ventricular cardiocytes (1.5 x 10(6)/mL) exposed to 30 min anoxia (95% N2/5% CO2) and 0, 3, 20, and 45 min of reoxygenation (95% O2/5% CO2). In addition to preventing lipid peroxide formation, propranolol maintained cellular viability, and minimized ultrastructural alterations. In the absence of propranolol, the outer mitochondria become swollen and rounded up within the first few minutes of reoxygenation. The perinuclear mitochondrial area increased only slightly. We observed that the cellular injury process proceeded differentially from the exterior to the interior, with a mitochondrial area increase and outer membrane rupture. Sarcolemmal damage was also observed with prevalent blebbing and membrane loss. The Z-lines became wider and more diffuse with reoxygenation. Injury to the nuclear double membrane was observed. Incubation with propranolol showed significant protection during postanoxia reoxygenation. In contrast, the more water soluble beta-blocker atenolol only exhibited slight protection. In addition, d-propranolol (the non beta-blocking isomer) and the antioxidant enzymes, SOD and catalase, showed significant protection. These data support previous findings concerning the antioxidant properties of propranolol which appear to be independent of beta-receptor blockade. PMID- 1937139 TI - Is the lens canned? AB - The ocular lens somehow remains pellucid despite bombardment by ultraviolet radiation and endogenous hydrogen peroxide (present in the humoral fluids which bathe this tissue). The lens and adjacent aqueous and vitreous humors contain exceptionally high concentrations of reducing substances, particularly ascorbic acid, thought to be important in lenticular oxidant defense. However, in the presence of traces of transition metals, or when exposed to ultraviolet radiation, ascorbic acid readily reacts with oxygen, yielding hydrogen peroxide, and damaging lens crystallins. We propose the alternative hypothesis that the real antioxidant function of ascorbic acid, particularly that in the aqueous and vitreous humors, may be effecting the conversion of oxygen to water. Because the lens lacks a blood supply, coupled reactions of ascorbic acid with oxygen in the humoral fluid spaces should produce a metabolically sustained anaerobiosis. If so, nature may have preinvented the process of canning, wherein food (or in this case, the lens) is preserved by a combination of sterility and anoxia. PMID- 1937140 TI - Vitamin E and oxidative stress. AB - Oxidative stress can result from or be enhanced by a large variety of conditions, including nutritional imbalance, exposure to chemical and physical agents in the environment, strenuous physical activities, injury, and hereditary disorders. While many enzymes and compounds are involved in protecting cells from the adverse effects of oxidative stress, vitamin E occupies an important and unique position in the overall antioxidant defense. The antioxidant function of vitamin E is closely related to the status of many dietary components. Vitamin E-depleted animals are generally more susceptible to the adverse effects of environmental agents than supplemented animals. Also, vitamin E supplementation is beneficial to certain groups of the population. However, supplementing vitamin E in experimental subjects maintained on a nutritionally adequate diet does not always provide additional protection. Differential metabolic responses in various organs and differences in experimental conditions often contribute in the discrepancies in the literature. The lack of clear evidence for the occurrence of lipid peroxidation or antioxidant function of vitamin E in vivo can be attributed partly to the presence of active pathways for metabolizing hydroperoxides, aldehydes, and other oxidation products. Specific and sensitive techniques for measuring lipid peroxidation products in biological systems are essential for understanding the role of free radical-induced lipid peroxidation in tissue damage and antioxidant function of vitamin E in vivo. PMID- 1937141 TI - HSP70 and other possible heat shock or oxidative stress proteins are induced in skeletal muscle, heart, and liver during exercise. AB - Exercise causes heat shock (muscle temperatures of up to 45 degrees C, core temperatures of up to 44 degrees C) and oxidative stress (generation of O2- and H2O2), and exercise training promotes mitochondrial biogenesis (2-3-fold increases in muscle mitochondria). The concentrations of at least 15 possible heat shock or oxidative stress proteins (including one with a molecular weight of 70 kDa) were increased, in skeletal muscle, heart, and liver, by exercise. Soleus, plantaris, and extensor digitorum longus (EDL) muscles exhibited differential protein synthetic responses ([3H]leucine incorporation) to heat shock and oxidative stress in vitro but five proteins (particularly a 70 kDa protein and a 106 kDa protein) were common to both stresses. HSP70 mRNA levels were next analyzed by Northern transfer, using a [32P]-labeled HSP70 cDNA probe. HSP70 mRNA levels were increased, in skeletal and cardiac muscle, by exercise and by both heat shock and oxidative stress. Skeletal muscle HSP70 mRNA levels peaked 30-60 min following exercise, and appeared to decline slowly towards control levels by 6 h postexercise. Two distinct HSP70 mRNA species were observed in cardiac muscle; a 2.3 kb mRNA which returned to control levels within 2-3 h postexercise, and a 3.5 kb mRNA species which remained at elevated concentrations for some 6 h postexercise. The induction of HSP70 appears to be a physiological response to the heat shock and oxidative stress of exercise. Exercise hyperthermia may actually cause oxidative stress since we also found that muscle mitochondria undergo progressive uncoupling and increased O2- generation with increasing temperatures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937142 TI - Characterization of a more electronegatively charged LDL subfraction by ion exchange HPLC. AB - Low density lipoproteins (LDL), collected from 32 normal male subjects (aged 30 60), were subfractionated by high resolution ion exchange chromatography (IE HPLC). By this procedure two LDL subfractions were eluted. The first corresponds to normal LDL (nLDL); while the second one corresponds to a more electronegative subfraction, called LDL-. The mean percentage contribution of LDL- to native plasma LDL was of 3.9% (range 0.5-9.8%). The percentage concentration of LDL- in total native LDL did not correlate with plasma total cholesterol, triglycerides, and LDL cholesterol, whereas a significant negative correlation with high density lipoprotein cholesterol was found (r = -.38; p less than .05). LDL- was negatively correlated with LDL phospholipids (r = -.59; p less than .001), and with the LDL vitamin E content (r = -.63; p less than .001), and positively correlated with LDL proteins (r = -.35; p less than .05) and the content of thiobarbituric acid reactive substances (TBARS) in total LDL (r = .43; p less than .05). The TBARS molar content of LDL- was three times higher than in nLDL, with a mean concentration in LDL- of 7.3 mol/mol lipoprotein. By preparative IE HPLC significant differences of the LDL- chemical composition were observed. The percentage content of cholesterol esters and of phospholipids was decreased, whereas proteins and free cholesterol were increased. Analysis by sodium dodecyl sulphate polyacrylamide gel electrophoresis revealed that besides apolipoprotein B-100 there was evidence of peptides with a higher molecular weight in LDL .(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937143 TI - Direct and continuous measurement of hydroperoxide-induced oxidative stress on the membrane of intact erythrocytes. AB - Having minimized spectroscopic interference by hemoglobin (Hb), peroxidation processes in intact erythrocytes could be monitored in a continuous assay using the fluorescent polyunsaturated fatty acid, parinaric acid (PnA), as a peroxidation probe. Control experiments to establish the character of the method are described in detail. As a practical application, comparative studies were performed to monitor the response of normal and sickle Hb-containing human erythrocytes to oxidative stress in the PnA assay. After 10 min of incubation with 200 microM cumene hydroperoxide (cumOOH), peroxidation of PnA was found to be enhanced in erythrocytes from sickle cell disease patients (SS: 48 +/- 9% (n = 6) of initial amount had been peroxidized) compared to healthy controls (AA: 30 +/- 4% (n = 9)). PnA peroxidation in erythrocytes from sickle cell trait individuals (AS: 30 +/- 3% (n = 4)) was equal to that in control cells. The increased oxidation of PnA in sickle erythrocytes was accompanied by enhanced oxidation of Hb (metHb and hemichrome formation), indicating that sickle Hb mediates enhanced cumOOH-derived radical generation. It is concluded that PnA can be a useful tool in studying membrane peroxidation processes in intact normal and pathological erythrocytes. PMID- 1937144 TI - Hypoxia/reoxygenation alters endothelial prostacyclin synthesis--protection by superoxide dismutase. AB - An in vitro model was designed to study the role of ischemia/reperfusion and oxygen free radicals on vascular prostacyclin (PGI2) synthesis and protection provided by superoxide dismutase (SOD). Cultured bovine aortic endothelial cells (BAEC) were subjected to various times of hypoxia (30 min to 5 h) followed by 30 min reoxygenation. An increase or a decrease in PGI2 synthesis capacity was then observed according to the duration of hypoxia. Inhibition of PGI2 synthesis after 5 h hypoxia/30 min reoxygenation was accompanied by a rise in lipoperoxidation products and a slight cytotoxicity. Superoxide anion could be implicated in these cellular alterations as SOD efficiently prevented these effects. Incubation of normoxic or H/R-treated BAEC with SOD led to an increase in cellular SOD activity as compared to controls. This increase, inhibited by incubation at 4 degrees C but not by addition of cycloheximide, strongly suggested endocytosis of SOD. This study emphasizes the role of endothelium as a source and target of free radicals and provides a new insight into the mechanism of protection by SOD in ischemia related vascular pathology. PMID- 1937145 TI - DNA damage by smoke: protection by turmeric and other inhibitors of ROS. AB - Twigs-dry leaves smoke condensate (TDS), as a source of clastogenic ROS and carcinogenic PAH, was investigated for its in vitro DNA-damaging effect in calf thymus DNA and human peripheral lymphocytes. An aqueous turmeric component--Aq.T- with an established antioxidant activity, was tested as a DNA protectant. TDS induced 13-fold damage to calf thymus DNA as judged by the emergence of a DNA damage specific, fluorescent product (em: 405 nm). Aq.T at 800 ng/microL extended 69% protection to calf thymus DNA and was comparable to the other protectants such as curcumin, BHA, vitamin E, SOD, and CAT. In human peripheral lymphocytes, TDS induced extensive DNA damage in comparison with the tumor promoter TPA, as judged by FADU. Aq.T at 300 ng/microL extended 90% protection to human lymphocyte DNA against TDS-induced damage, and was more effective than the other protectants -DABCO, D-mannitol, sodium benzoate, vitamin E (ROS quenchers), SOD, CAT (antioxidant enzymes), tannic acid, flufenamic acid, BHA, BHT, n-PG, curcumin and quercetin (antioxidants). Aq.T offered 65% protection to human lymphocyte DNA against TPA-induced damage and was comparable to SOD. The above results indicate that TDS induces substantial DNA damage in calf thymus DNA and human lymphocytes and Aq.T is an efficient protectant. PMID- 1937146 TI - Transport kinetics for superoxide dismutase and catalase between plasma and interstitial fluid in the rat small intestine. AB - The purpose of these studies was to determine the initial rates (first 5 h) of plasma-to-interstitial fluid transport for superoxide dismutase, catalase, and albumin in the rat small intestine. In all experiments, the renal vascular pedicles were ligated to prevent the renal excretion of these macromolecules. Plasma and intestinal interstitial fluid (lymph) samples were collected at timed intervals after bolus intravenous administration of SOD, catalase, or 125I labeled albumin. Before injection of the proteins, the plasma concentrations (43.8 +/- 16.9 and 7.6 +/- 1.2 U/mL, respectively), interstitial fluid (lymph) concentrations (28.8 +/- 7.6 and 1.6 +/- 0.8 U/mL, respectively), and the lymph to-plasma (L/P) protein concentration ratios (0.59 +/- 0.13 and 0.22 +/- 0.09, respectively) for endogenous SOD and catalase were determined. The plasma disappearance rate for exogenously administered catalase far exceeded the rates for SOD or albumin. However, the rate of catalase disappearance from the plasma was markedly reduced in animals in which the circulation through the liver was eliminated, suggesting that the hepatic route may be important for elimination of exogenously administered catalase. Maximal interstitial fluid catalase concentrations were achieved within 30 min while SOD and albumin required 45-90 min. The L/P ratios for exogenously administered SOD and albumin increased to 0.22 +/- 0.06 and 0.19 +/- 0.03 within 60 and 120 min of injection, respectively, and remained at these levels for the remainder of the experimental protocol. The catalase L/P ratio increased to 0.24 +/- 0.07 within 90 min of injection and subsequently declined to levels measured for endogenous catalase over the remaining 3.5 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937147 TI - Increased SOD activities and decreased lipid peroxide levels induced by low dose X irradiation in rat organs. AB - After a single exposure to doses ranging from 0.05 to 0.50 Gy, the SOD activities in immune organs of the irradiated rats, at 4 h after whole-body X irradiation, showed significant increases by 50 to 90% (hereinafter p less than 0.05) in comparison with the control groups. The dose in the brain and liver showed tendencies to increase by 30 to 50% for doses ranging from 0.50 to 2.50 Gy. The levels of TBARS (lipid peroxides) in immune organs decreased significantly by 20 to 50% in contrast with the control groups for doses ranging from 0.10 to 1.00 Gy. Decreases by 20 to 30% were observed in brains and livers for doses near 0.50 Gy. When the dose was 0.25 Gy, the SOD activities in the spleen showed a persistent radiation-induced increase for at least 12 weeks, livers for 8 weeks, brains and thymuses for 4 weeks, and bone marrows for about 1 week. The TBARS levels in the brain and thymus showed persistent decreases due to irradiation for at least 12 weeks, and those in bone marrows for 8 h. PMID- 1937148 TI - Early increase in intracellular calcium during photodynamic permeabilization. AB - The purpose of this study was to determine if there was an early increase in intracellular Ca++ which preceded generalized lysis of thymocytes during photodynamic permeabilization. A method was developed that facilitated the simultaneous measurement in real time of permeabilization of the thymocyte cell membrane to Ca++, Mn++, and ethidium bromide during photodynamic action. Quin-2 loaded cells were illuminated in the presence of erythrosin B and the change in the fluorescence emission of the calcium-quin-2 complex was used to determine how soon and to what extent intracellular Ca++ changed following illumination. In the presence of extracellular manganese, the same system was used to determine how soon the cells became permeable to Mn++ or quin-2. It was determined that the fluorescence emission of the ethidium bromide-DNA complex was strong enough to be measured in the presence of the calcium-quin-2 complex. This enabled the concomitant determination of the elapsed time following illumination before ethidium bromide entered the cell. It was established that increased intracellular Ca++ was an early event in the photodynamic permeabilization of thymocytes that preceded permeabilization of the cell membrane to ethidium bromide, Mn++ or quin-2, or lysis. PMID- 1937149 TI - Reperfusion-induced arrhythmias are not prevented by uric acid in the isolated rat heart. AB - Oxygen-derived free radicals have been implicated in ventricular arrhythmogenesis during coronary reperfusion following an acute ischemic event. We have investigated the possibility that uric acid, a potentially important physiological antioxidant (inhibits lipid peroxidation and scavenges various radical species during oxidation to allantoin), or oxonic acid (inhibitor of uricase enzyme), are able to prevent reperfusion-induced ventricular dysrhythmias in isolated buffer-perfused rat hearts. Rat hearts (n = 12/group) underwent 15 minutes occlusion; arrhythmias were monitored during ischemia and for 10 minutes of reperfusion. There was no difference in the incidence of ventricular fibrillation or ventricular tachycardia in either uric acid or oxonic acid treated hearts compared to untreated controls. Mean duration of ventricular fibrillation appeared to be reduced in hearts treated with 10(-3) and 10(-4) M oxonic acid compared to controls but these data did not achieve a level of statistical significance. These results demonstrate that uric acid and oxonic acid failed to prevent reperfusion-mediated ventricular dysrhythmias in this experimental preparation. Although oxygen-derived free radicals may contribute to the initiation of either ischemia- or reperfusion-induced arrhythmogenesis, our findings provide little support for this hypothesis. PMID- 1937150 TI - Oxidative effects of laser photocoagulation. AB - Diabetic proliferative retinopathy is a common and sight-threatening condition. Oxidative stress is an integral and possibly causative part of the pathogenesis. Although laser photocoagulation is usually a beneficial treatment it remains unclear how it works. The possibility that it induces a sudden, temporary increase in free radical activity either by direct thermal damage or by oxygen reperfusion is explored in this clinical study by measuring the oxidative status in the peripheral blood of 13 patients undergoing panretinal photocoagulation. There were significant increases at one hour in malondialdehyde-like material (MDA-LM), 8.1 (6.9-9.6) nmol/mL, to 9.1 (7.6-9.8) nmol/mL, (less than 0.005); plasma thiols (PSH), 423 (352-457) microns/L, to 444 (382-478) microns/L, (p less than 0.005) and red cell reduced glutathione (GSH), 1357 (1295-1655) microns/L, to 1480 (1305-1760) microns/L, (p less than 0.01). Diene conjugates rose over the first hour 0.55 (0.36-0.79) od/mL, to 0.58 (0.34-0.85) od/mL falling to 0.56 (0.36-0.79) od/mL at 2 h but these changes were not significant. At 2 h, MDA-LM 8.4 (6.7-9.6) nmol/mL and PSH 404 (379-462) microns/L had returned to baseline but GSH remained significantly elevated 1500 (1325-1675) microns/L, (p less than 0.005 compared to baseline). This is a new observation and in some circumstances such generation of free radicals could explain the mechanism behind the complications of photocoagulation by direct or indirect damage to vascular endothelium leading to increased vascular permeability manifest as macular oedema or choroidal effusions. PMID- 1937151 TI - [Diazepam versus midazolam for "wakeful sedation" in oral surgery]. AB - I.v. midazolam was compared with diazepam in 112 dental outpatients in order to obtain a control of sedation. Midazolam has shown better results in all the parameters evaluated (memory scale, pharmacokinetics and pharmacodynamics values) and in controlling sedation. The Authors consider midazolam as a preferred drug in dental outpatients and hope to get it available also in Italy. PMID- 1937152 TI - [Conscious sedation in dentistry--nitrous oxide]. PMID- 1937153 TI - [Comparative evaluation of propofol and thiopentone for induction of general anesthesia in dentistry]. AB - For dental and stomatologic operations of short duration the Authors can consider "propofol" as the best hypnotic, because it is gifted with hypnotic inducing properties, which have a remarkable speed of recuperation, characterised by the subject's sensation of well-being, and, with modest respiratory depression and maintenance of cardiovascular values. PMID- 1937154 TI - [Intravenous administration]. PMID- 1937155 TI - The twin block technique. PMID- 1937156 TI - Use of the 'indicator line' to assess maxillary position. PMID- 1937157 TI - Eruption of impacted maxillary cuspid. PMID- 1937158 TI - [Transfusion of blood and blood products]. PMID- 1937159 TI - [Acetylsalicylic acid and pregnancy hypertension]. PMID- 1937160 TI - [Prostaglandins in uterine atony]. PMID- 1937162 TI - [Adjuvant chemotherapy in breast and ovarian carcinoma]. PMID- 1937161 TI - [Antibiotics in premature rupture of the fetal membranes]. PMID- 1937163 TI - [Cerclage in cervix insufficiency]. PMID- 1937165 TI - [Glycosuria in pregnancy]. PMID- 1937164 TI - [Medical prevention of respiratory distress syndrome]. PMID- 1937166 TI - Quantitative platelet imaging and comparison of four mathematical models for the evaluation of platelet mean life span in patients with chronic immune thrombocytopenia. AB - BACKGROUND AND METHODS: Twenty-five thrombocytopenic patients underwent quantitative in vivo platelet kinetic studies using a scintillation camera and a computer-assisted imaging system. They fulfilled the criteria for chronic immune thrombocytopenia, and the object of the study was to evaluate platelet sequestration and destruction in the spleen. In this sense, the differences in the distribution of the radiolabelled platelets in the spleen and the liver, as well as the differences in the platelet mean life span (MLS) as computed by different methods were assessed. Serial images of the spleen pool, liver and heart were taken after reinjection of In-111-oxine labelled autologous platelets. RESULTS AND CONCLUSIONS: The spleen/liver ratio proved to be a more reliable index in indicating the splenectomy outcome that the Z index (see text). Platelet survival curves were analyzed using four mathematical models, and it was found that MLS estimation is model dependent. Thus, it seem advisable to apply at least two different methods when analyzing experimental data. PMID- 1937167 TI - Cytogenetics of infantile leukemias and its correlations with bio-clinical features. The "G. Gaslini" Children's Hospital experience over a 9-year period. AB - BACKGROUND AND METHODS: Infantile leukemia is a rare disorder, and few cytogenetic studies have been performed on this condition. RESULTS AND CONCLUSIONS: The authors present the cytogenetic analyses performed on 14 cases of infantile leukemia. The most frequent chromosomal changes are rearrangements involving 11q (4 cases) and gains of one or more chromosomes 21. Patients with chromosomal rearrangements show a worse prognosis than those with only hyperdiploidy or a normal karyotype, although the difference was not statistically significant due to the small size and short median follow-up. PMID- 1937168 TI - Prognostic significance of serum albumin in chronic lymphocytic leukemia. AB - BACKGROUND: Low levels of serum albumin have been reported to be associated with a poor prognosis in lymphoproliferative disorders. METHODS AND RESULTS: Clinical and laboratory data were retrospectively evaluated in a series of 342 patients with chronic lymphocytic leukemia (CLL). In univariate analysis, survival was significantly influenced (p less than 0.01) by traditional prognostic factors: number of lymphoid areas involved, volume of adenopathies, presence and degree of hepatomegaly and splenomegaly, anemia, thrombocytopenia, peripheral blood lymphocytosis (greater than 60 x 10(9)/l), percentage of bone marrow lymphocytes (greater than 50%). Among variables not included in the traditional staging systems, age over 70, hypoproteinemia (less than 6 gr/dl) and hypoalbuminemia (less than 3.5 gr/dl) adversely affected prognosis. All the most widely adopted staging systems recognize no more than three groups of patients with statistically different outcomes. In multivariate analysis, the prognostic value of serum albumin was independent of both age and the group of variables included in each staging system considered. CONCLUSIONS: We suggest that evaluation of the serum albumin level could be useful, in future multicenter studies, for further implementation of the staging of CLL. PMID- 1937169 TI - Pharmacokinetics of high-dose cyclophosphamide for bone marrow transplantation. AB - BACKGROUND: Despite the fact that high-dose cyclophosphamide (CP) is currently used for both cancer treatment and bone marrow transplantation, its pharmacokinetics is not well defined. METHODS: Serum and urine concentrations of CP were determined in 19 patients who received 2 or more high doses of CP before bone marrow transplantation. RESULTS: Urinary recovery ranged between 1% and 32% and was essentially the same after the first and the second CP dose. In contrast, the pattern of disappearance from the serum of the two doses of CP was substantially different. The serum half-life of the first dose varied over a wide range (4.4 to 25.0 h, mean 8.7 +/- 4.6 h), while the half-life of the second dose was always shorter (1.7 to 6.0 h, mean 3.6 +/- 0.9 h). Accordingly, the CP area under the curve (AUC) of the first dose was much more variable and was always much higher than the CP AUC of the second dose. Therefore, prior administration of CP resulted in a very significant increase of CP metabolism. CONCLUSIONS: These differences can be relevant to the outcome of treatment, and suggest that the metabolism of CP can be manipulated and can be made more homogeneous, either by giving a priming dose of CP (leading to a lower CP AUC, to a faster conversion into activated metabolites and to the exposure of host cells to a higher concentration of the metabolites for a shorter time) or by giving the drug as a continuous infusion over a longer time, to obtain the opposite results. PMID- 1937170 TI - Different suppression of Ph1 positive hemopoiesis induced by intensive chemotherapy in lymphoid and myeloid blast crisis of CML. AB - BACKGROUND: The suppression of Ph1-positive hemopoiesis is a major goal in the treatment of CML; in this context the CML patients in blast crisis obtaining a complete clinical remission represent a useful model to investigate the behavior of the Ph1-positive and negative clones during bone marrow repopulation after ablative therapy. METHODS: Seven CML patients in blast crisis (four lymphoid and three myeloid) who obtained a complete clinical remission after an intensive polychemotherapy treatment were evaluated by cytogenetic and molecular analysis both in blast and remission phases. Standard cytogenetic and Southern techniques were employed; in addition, minimal residual disease status (MRD) was ascertained by amplification (PCR) of the specific bcr-abl chimeric transcripts. RESULTS: After a single cycle of induction, all lymphoid cases displayed a complete restoration of Ph1-negative hemopoiesis; by contrast, one myeloid blast crisis showed a partial suppression of Ph1-positive hemopoiesis only after two cycles of chemotherapy, and in the remaining two cases the hematological remission was indeed a reversion to the chronic phase. CONCLUSIONS: Ph1-positive chronic clones present in lymphoid blast crisis showed a higher degree of sensitivity to intensive chemotherapy than those present in the myeloid cases. This observation further suggests that the growth properties of the Ph1-positive clones are highly variable from case to case and probably tend to progress during the time-course of the disease. PMID- 1937172 TI - Infections in haematologic neoplasms: autopsy findings. AB - BACKGROUND AND METHODS: Infections are the main cause of death in most haematologic malignancies. We studied 95 autopsies of patients who died from haematologic neoplasms in the period 1980-1989 at Niguarda Ca Granda Hospital. RESULTS AND CONCLUSIONS: Infections were the cause of death in 63% of patients. In this group of patients bacterial infections accounted for 43% of deaths; fungal infections were frequent too (28%), mainly among leukemic patients; viral (9%), mycobacterial (7%) and polymicrobic infections (11%) were also documented. Haemorrhages were less frequently fatal (12%) due to the availability of haemocomponents. A high number of fatal haemorrhages were associated with fungal infections. Neoplastic progression was the real cause of death in only a few cases, and cardiovascular and pulmonary complications were fatal in the great majority of the other patients. PMID- 1937171 TI - Toxic effects of high-dose deferoxamine treatment in patients with iron overload: an electrophysiological study of cerebral and visual function. AB - BACKGROUND AND METHODS: It is well known that deferoxamine (DFO) treatment in thalassemia major can produce ocular toxicity. In one experience, Visual evoked potentials (VEPS) to pattern reversal were formed to be altered in 4 out of 10 patients under conventional treatment with DFO, before supplementary high-dose i.v. deferoxamine. In all 4 cases the alterations consisted of bilaterally delayed P100 latency, always obtained by stimulation with high spatial frequency (15' checks) and associated in three cases with low spatial frequency (55'). Computerized EEG (cEEG) studies showed a generalized increase of slowing activity. All patients underwent high-dose DFO treatment. RESULTS: At the control performed at the end of treatment in all 4 cases with previous VEP alterations, a further delay in P100 latency was observed bilaterally while two of the six patients, without previous involvement, showed delayed responses when using checks of 15'. The EEG slowing activity was not modified. Three weeks after terminating i.v. DFO therapy, the patients were still under subcutaneous treatment (50 mg/kg/day); a more evident VEP recovery towards the initial values was observed in those patients without initial alterations. No significant changes were found between electrophysiological parameters and serum ferritin levels. CONCLUSIONS: Our results indicate that high-dose DFO therapy in patients with iron overload induces reversible visual impairment without significant changes in brain electrical activity. The employment of VEP in intensive chelation programs in thalassemia major is discussed. PMID- 1937174 TI - Periodic acid Schiff (PAS) positivity in fetal erythroblasts. AB - The smears of 26 fetal blood samples taken for prenatal diagnosis were stained for the PAS reaction. Twelve out of 26 cases were subsequently found to be normal and 14 were found to be affected by different abnormalities; 83.4% of normal cases and 92.8% of abnormal cases showed moderate positivity to the PAS reaction. A higher percentage of PAS positive erythroblasts was found in the abnormal cases (p less than 0.01). Five cases with a percentage greater than 10% also showed a very high percentage of erythroblasts. No linear correlation was found between PAS positivity and erythroblastosis either in the normal or the abnormal cases, but pooling them resulted in a correlation between PAS positivity and erythroblastosis (r = 0.536; p less than 0.005). PAS positivity was most often diffuse and scored 1+. Since erythroblastosis is considered an indirect sign of fetal liver erythropoiesis, the hepatic environment and its peculiar hemopoiesis could play a role in producing a cohort of PAS positive erythroblasts. PMID- 1937173 TI - HIV-related thrombocytopenia: a therapeutical update. AB - HIV-seropositive patients who belong to the three major acquired immunodeficiency syndrome (AIDS) risk groups may develop an idiopathic thrombocytopenic purpura (ITP) which is related to the HIV infection. HIV-associated ITP clinically resembles classic ITP but, in spite of very low platelet numbers, bleeding is rarely severe, and moderate splenomegaly and lymphadenomegalies are seldom present. Treatment is the same as that given for classic ITP because the pathogenesis is in many ways similar. Immunosuppressors can be dangerous in the case of retrovirosis, and splenectomy may lead to AIDS. High doses of immunoglobulins often give an improved platelet count but this tends to be short lived, and long-term periodical infusions usually lose therapeutical effect. Alpha interferon gives conflicting results and Danatrol is not usually effective. Specific anti-D immunoglobulins produce a high percentage of positive results and may be administered for long-term maintenance without side effects. Zidovudine (AZT) may produce a good platelet increase in a large number of patients, but there is no consensus for the use of this anti-retroviral drug in otherwise asymptomatic HIV-positive patients. In conclusion, since it is very unusual for bleeding to occur, moderate thrombocytopenia is best left untreated because a spontaneous increase in platelet count is possible. But if the platelet count is very low, or if bleeding is present, treatment is mandatory and must produce a rapid platelet increment with minimal side effects. PMID- 1937175 TI - Standardized format for abbreviations and units to be used when expressing blood count results. International Committee for Standardization in Haematology. PMID- 1937176 TI - Corticosteroids in the treatment of thrombotic thrombocytopenic purpura (TTP) PMID- 1937177 TI - Acute lymphoblastic leukemia and eosinophilia. PMID- 1937178 TI - Human peripheral blood mononuclear cell subfractionation using counterflow centrifugation elutriation. AB - BACKGROUND: Counterflow Centrifugation Elutriation (CCE) can be used to separate different amounts of cells into distinct subpopulations on the basis of different sedimentation characteristics. It was the aim of this study to evaluate CCE as a technique for fractionation of normal human peripheral blood. METHODS: Human peripheral blood mononuclear cells (PBMC) were separated into three fractions by means of CCE. RESULTS: The first two fractions, eluted at a flow rate of 21 ml/min and 25 ml/min, respectively, were composed of lymphocytes with less than 2% and 4% contaminating monocytes. The cells in these fractions were capable of responding to T-cell mitogens, such as phytohemagglutinin (PHA). The third fraction, collected at the termination of the run, was composed predominantly (greater than 85%) of large monocytes that strongly labelled leu-M3 (CD 14); these cells were unable to respond to PHA stimulation. The cell recovery after CCE was considerably high (greater than 93%), and all fractions retained high cell viability (greater than 96%) and were available for further manipulation. CONCLUSIONS: In conclusion, our data demonstrate that CCE is a technique suitable for large-scale separations that makes highly purified cell fractions available for further manipulation. PMID- 1937179 TI - An assessment of the operating characteristics of Coulter Counter Model S-Plus STKR. AB - BACKGROUND AND METHODS: The operating performance of the Coulter Counter S Plus STKR was evaluated in two hospital laboratories in Rome and in Florence. Experimental design conformed to both the ICSH and NCCLS Standards for the evaluation of hematologic analyzers, and to the ECCLS guidelines for the multicenter evaluation of analyzers in clinical chemistry. RESULTS AND CONCLUSIONS: Cell counts in K3 EDTA were unchanged over 6 hours at room temperature and 72 hours at 4 degrees C, while MCV, MPV and leukocyte differentials were far less stable. Carry over, precision and linearity met the manufacturer's specifications, while a satisfactory relative accuracy was demonstrated by determining reference values on an adult reference group and by comparing the instrument with the previous model S Plus IV D. The accuracy of the leukocyte differentials was evaluated by the microscope reference method, and our results seemed to validate the hypotheses that the STKR model counts: i) eosinophils, basophils and banded neutrophils among GR; ii) variant lymphocytes among LY, and iii) various abnormal cells among mononuclear cells. However, in spite of this statistical significance, some difficulties in correctly classifying the mononuclear population were demonstrated. PMID- 1937180 TI - [Lower limb replantation with primary foreshortening and secondary lengthening by callus distraction]. AB - Twenty-four lower limb replantations have been performed in our hospital since 1976. In three of these cases, subsequent foreshortening of the replanted lower limb was successfully treated by callus distraction. In all of these cases, an impressive functional improvement resulted. Ilizarov's method for callus distraction can be recommended in these cases. PMID- 1937181 TI - [Covering skin-soft tissue defects with a free forearm flap in exposed osteosynthesis material in the area of the lower leg]. AB - Soft tissue defects in the lower leg with exposed internal fixation plates frequently pose problems to the surgeon. Substantial defects in the distal lower leg should be covered by free tissue transplantation. Very good results can be achieved in such cases using the radial forearm flap. This flap can be used for covering exposed internal fixation plates in selected patients. The authors present four such cases. The flaps healed well in all cases and fracture healing was without delay. Bone fixation procedure did not have to be changed. PMID- 1937182 TI - Contour restoration in posttraumatic hemifacial asymmetry with microvascular omental free flap. A case report. PMID- 1937183 TI - [The "open palm" technique in Dupuytren's contracture]. AB - The authores reports on the "open-palm-technique" used in those patients in whom after excision of the Dupuytren's tissue and passive maximal extension of the fingers the skin in the palm cannot be closed without undue tension. Postoperative complications such as hematoma accumulation and edema can be avoided by this method. Neither the length of treatment nor the duration of incapacity is prolonged by this technique. PMID- 1937184 TI - [Intra-osseous epidermoid cyst]. AB - In contrast to epidermoid cysts under the skin of the palm and the fingers, intraosseous epidermoid cysts are very rare. They present in the terminal phalanges of the fingers and are posttraumatic in nature. Their clinical and X ray presentation is similar to enchondroma and pathological fractures do occur. When operating, one must remove the capsule to prevent recurrence. Bone grafting is usually not necessary after adequate curettage. Two typical cases are presented. PMID- 1937185 TI - [Premature maturation of the carpal bones as an early diagnostic sign of juvenile rheumatoid arthritis]. AB - A rare premature maturation of the carpal bones in combination with swelling and flexion contracture of the wrist is demonstrated in two cases of juvenile rheumatoid arthritis. The radiologically verified premature and asymmetrical maturation of the carpal bones was the earliest diagnostic sign in juvenile rheumatoid arthritis. PMID- 1937186 TI - [Experiences with continuous nerve block of the wrist]. AB - Continuous nerve blocks are effective analgesics for physiotherapy following operative procedures on gliding tissues. In the upper extremity, continuous axillary blocks are regularly used, leading to weak muscular action and even paralysis, although active muscle action is wanted. With continuous wrist blocks, extrinsic motor function of the hand remains undisturbed. Placement of a polyethylene catheter near the nerves with instillation of a local anesthetic (carbostesine 0.5, 3-4 ml per nerve) provides complete anesthesia of the hand without loss of extrinsic motor function. After 124 nerve blocks in 60 patients, no complications (infections, nerve irritations or lesions) have been observed. Continuous wrist blocks are indicated for postoperative treatment after tenolysis, joint mobilisation or arthrolysis, open reduction and internal fixation and in certain cases of chronic pain care. PMID- 1937187 TI - [Isolated compression of the dorsal branch of the ulnar nerve]. AB - The dorsal branch of the ulnar nerve was dissected in 20 upper extremities. The nerve arises from the ulnar aspect of the ulnar nerve at an average distance of 8.5 centimeters from the proximal border of the pisiforme. It courses deep to the palmar carpal ligament and pierces the ligament dorsal to the tendon of the flexor carpi ulnaris, becoming subcutaneous. The palmar carpal ligament has been found to be a cause of isolated entrapment of the dorsal branch of the ulnar nerve. A report of eleven operative cases is presented. PMID- 1937188 TI - [The value of early intervention in hand infections]. AB - The question whether delayed surgical treatment has any effect on recovery and invalidity in severe infections of the hand was evaluated in 91 cases. Immediate surgical treatment led to complete recovery in 90% of the cases, whereas surgical intervention one week later led to a significantly higher complication and amputation rate. PMID- 1937189 TI - [Evaluating occupational stress on the hand]. AB - In order to achieve objective data to eventually measure the dexterity of hands, we examined 210 hands in 105 persons. These persons were divided into two groups: one group of people with jobs demanding unusual dexterity (musicians, typists, etc.), and another group with average occupational demands on the hand. As expected, we found that hand length and breadth and wrist circumference are always greater in the dominant hand of any individual. The thumb and small finger are always longer in the dominant hand. Joints' active range of motion are significantly higher in individuals whose occupations were particularly demanding. PMID- 1937190 TI - [Teratological counseling in Israel]. AB - For the past 6 years this laboratory has offered counseling on external factors which may harm the fetus. The number of calls on the service doubles yearly. From 1987 through the first half of 1990 there were 1182 calls, about half from women and half from physicians, nurses, geneticists, etc., most during the first trimester. In 88% there was no increased risk for congenital malformations as a result of the exposure, or the increased risk was minimal. In only 6% of cases was there significant increased risk, well above the 3% found in pregnancies in general. In 6% we were not able to assess accurately fetal risk, although we could assume it was relatively small. Outcome of pregnancy was available in 27% of the cases. There was no increase in spontaneous abortions, prematurity, or congenital anomalies in pregnancies in which we had decided there was no increased risk for malformations. However, the number of cases is still too small for significant conclusions. Reliable information concerning factors which may influence the fetus is important in allaying fear and anxiety in families in which fetal risk is not increased. In cases in which fetal insult is suspected, appropriate means of prenatal diagnosis are suggested, and the option of terminating pregnancy is offered. PMID- 1937191 TI - [Experimental cochlear damage by neomycin ear drops]. AB - Damage caused by neomycin sulphate solution, identical in concentration to that in ear drops, was tested on the cochleas of 28 guinea pigs. Neomycin sulphate with dexamethasone sodium, and physiologic salt solutions were also tested. Only neomycin solutions damaged the cochlea, and even after only a single exposure. The damage after a single exposure was to the supporting cells and not to the hair cells. However, because of the importance of the supporting cells for normal hearing and because destruction of supporting cells leads to shedding of hair cells, the resulting functional impairment is similar. As a result of further exposure to neomycin the hair cells themselves are damaged, and there is also loss of cell hair. Damage to either the cells or to the hair causes hearing loss. From our work it is clear that in guinea pigs neomycin is absorbed from the middle ear into the inner ear and damages the cochlea. Increased exposure to neomycin increases the damage. PMID- 1937192 TI - [Sustained release verapamil in essential hypertension]. AB - The efficacy of sustained release verapamil (Ikapress) was investigated in 237 hypertensive patients of both sexes in a multicenter trial in family practice. There were 4 groups: patients without previous treatment and those treated with nifedipine, with atenolol, or with a combination of drugs. After 4-7 days of washout, all those with diastolic pressures of 95 mm Hg or above received once daily 240 mg of verapamil for 8 weeks. 27 cases had to be withdrawn because of adverse effects: weakness in 10, constipation in 6, rash in 4, impotence in 3, and in 4, other reasons. In 177 blood pressure was brought under control after 4 weeks of treatment. An additional 33 were controlled after 4 weeks of 360 mg of sustained release verapamil. Response to treatment was similar in the 4 trial groups. Mean systolic and diastolic pressures fell 19 and 16 mm Hg, respectively, and mean pulse rate decreased by 5 beats/min. Constipation was the only side effect reported by those who completed the trial. However, there was a significant reduction in initial scores for headache, dizziness, numbness and edema after 8 weeks of verapamil and all indices of quality of life were significantly improved. These included scores for general well-being, physical fitness, social activity, job fitness, sexual activity, sleep, concentration and mood. Scores for daytime sleepiness and fatigue also decreased significantly. Thus, sustained-release verapamil in a daily dose of 240-360 mg was shown to be an effective antihypertensive. It had few adverse effects and gave considerable improvement in quality of life. PMID- 1937193 TI - [Tumors at the skull base]. AB - Tumors at the skull base, usually benign, present diagnostic and therapeutic challenges. Thus they necessitate close cooperation between the departments of otolaryngology, head and neck surgery, neurosurgery, anesthesia and diagnostic radiology. We therefore set up a special team for diagnosis and treatment of such cases. 2 representative cases of benign tumors at the skull base operated through the combined middle cranial fossa--infratemporal fossa approach are presented in detail. PMID- 1937194 TI - [Staging of rectal carcinoma by endorectal ultrasonography]. AB - Staging of rectal carcinoma is essential for its management. 23 patients with rectal lesions were examined by endorectal ultrasonography. Of these 19 had rectal carcinoma and in 4 there was an abscess of the rectal wall, previously diagnosed by sigmoidoscopic biopsy. 10 of those with carcinoma were examined by computerized tomography as well, and 10 were operated on. In most cases the staging of rectal carcinoma by endorectal ultrasonography was accurate and compared well with the operative histological results. We conclude that endorectal ultrasonography is the method of choice for staging of rectal carcinoma prior to treatment. PMID- 1937196 TI - [Clinical significance of antineutrophil cytoplasmic antibody]. PMID- 1937195 TI - [Familial infantile myasthenia gravis]. AB - The several forms of myasthenia gravis that occur in infancy include transient neonatal myasthenia, congenital myasthenia, and familial infantile myasthenia gravis. The latter is inherited in an autosomal recessive pattern. Severe episodes of respiratory distress are frequent in infancy, and are often provoked by mild respiratory infections. 2 sisters with congenital myasthenia gravis are described. Probably 2 other sisters died of the same disease, but no definite diagnosis was made in their cases. PMID- 1937197 TI - [Corticosteroids in fat embolism syndrome: treatment and prevention]. PMID- 1937198 TI - [Sudden cardiac death: etiology, pathogenesis and treatment]. PMID- 1937200 TI - [Diabetic septic foot]. PMID- 1937199 TI - [Contribution of thallium-201 scintigraphy to the diagnosis and assessment of patients with coronary artery disease]. PMID- 1937201 TI - [Animal experiments]. PMID- 1937202 TI - [Respiratory manifestations of connective tissue disease]. PMID- 1937203 TI - [Extreme weakness and shortness of breath in congestive cardiomyopathy]. PMID- 1937204 TI - [Second line for agents in the treatment of rheumatoid arthritis]. PMID- 1937205 TI - [Neonatal circumcision--update]. PMID- 1937206 TI - [The jittery newborn]. PMID- 1937207 TI - [Women entering medicine: implications for health care in Israel]. AB - An increasing number of women have been entering the medical profession during the past 2 decades. In all 4 medical schools in Israel, 46% of the students in 1989 were women, as were 30% of hospital residents. However, only a few women have reached top academic posts. With the increasing growth of immigration from the Soviet Union, a further increase in the number of women physicians is expected. However, half of the hospital-based residents of both sexes have similar specialty paths in pediatrics and medicine, but there are significant differences with regard to the other specialties: more men choose hospital-based surgical specialties, while women usually enter family medicine and psychiatry, mostly in an out-patient setting. These findings are compatible with other studies in Israel and abroad which reflect women's greater compassion and ability to communicate with patients and their families, as compared to men. Male physicians are more competitive and tend to seek professional status, power and practical rewards. It is anticipated that these trends will influence the nature and the education of the medical profession in the direction of a more humane type of medicine. PMID- 1937208 TI - [Alternating rifampicin and ceftriaxone for Neisseria meningitidis eradication in contacts]. AB - Following the occurrence of a case of meningococcal disease in a kibbutz, extensive preventive measures were instituted, consisting of alternate courses of rifampicin (10 mg/kg for 2 consecutive days) and ceftriaxone (single IM injection of 125 mg). Throughout the observation period Neisseria meningitidis was absent from oropharyngeal secretions of all those treated, but was found in those of an untreated control group. The alternate use of rifampicin and ceftriaxone should be considered for the long-term prevention of the occurrence of oropharyngeal carriers of Neisseria meningitidis. PMID- 1937209 TI - [Viper envenomation by Echis coloratus]. AB - Clinical and therapeutic experience with 24 cases of envenomation by Echis coloratus, the Mideast saw-scaled viper, is reported. These cases were seen between 1979-1989 at this hospital (Mt. Scopus). A clinical classification is proposed, based on severity of the bleeding diathesis and platelet count at presentation. It is suggested as a predictor of clinical outcome and as a guide to whether antiserum should be administered. PMID- 1937210 TI - [External cardiac pacing in a mobile intensive cardiac care unit]. AB - External cardiac pacing has recently been reintroduced as an effective method in emergency cardiac stimulation. We report for the first time the results of external cardiac pacing in a mobile intensive cardiac care unit. In 9 of 10 patients treated during the first 3 months of 1990, effective pacing was achieved. We conclude that external cardiac pacing is a rapid, safe and effective means of temporary pacing during emergency treatment, before admission to hospital. PMID- 1937211 TI - [Closure of postoperative anastomotic fistulas with a somatostatin analogue]. AB - Postoperative gastrointestinal fistula formation is not rare, and is accompanied by considerable morbidity and mortality. Somatostatin, a potential, universal endocrine and exocrine inhibitor, is a peptide synthesized in the nervous system and the gastrointestinal tract. We describe 2 men, 58 and 53 years old, respectively, with postoperative fistulas, the first after pancreatic-jejunal and the second after jejunal anastomosis. 7 and 3 days, respectively, after starting a synthetic somatostatin analogue (SMS 201-995), discharge from the fistulas decreased and they closed completely. PMID- 1937212 TI - [Injury proneness: the physiatric and psychiatric view points]. AB - Proneness to injury is a natural inclination with many causes: psychological, physical, physiological and social. We describe 9 patients with this problem. Most injuries, usually the result of falls, occur in 3 populations: young sports persons, workmen, and the elderly or those with chronic disorders. By analyzing the cases we can identify those prone to accidents and injury so as to improve prevention. PMID- 1937213 TI - [Anemia in children: hemoglobin changes in mild, acute infections]. AB - Anemia is commonly discovered in children when a complete blood count is routinely performed during acute and febrile illnesses. In this study-recovery of hemoglobin levels in children after acute infections was evaluated. Hemoglobin levels were measured in capillary blood of 70 patients who visited a community primary pediatric clinic with an acute infectious illness (37 boys, 33 girls; mean age 22 months, mode 18; 58 had fever of 38 degrees or higher). The most frequent diagnoses were upper respiratory tract infection, acute otitis media and pharyngitis. Follow-up hemoglobin measurements were performed after at least 3 days without fever and when the children were considered well by their parents. The average time between the 2 measurements was 12 +/- 9 days. PMID- 1937214 TI - [Postmenopausal estrogen therapy and cardiovascular disease]. PMID- 1937215 TI - [Regulation of IgE biosynthesis: new approach for treatment of allergic disorders]. PMID- 1937217 TI - [Sarcoma of the breast]. PMID- 1937216 TI - [Raynaud's phenomenon: can we predict systemic disease?]. PMID- 1937218 TI - [Measures of morbidity and mortality in epidemiological research]. PMID- 1937220 TI - [Cancer to cancer metastasis]. PMID- 1937219 TI - [Vegetarianism, veganism and trace elements (iron, zinc and copper)]. PMID- 1937221 TI - [An inquiry into the spiritual death of Dr. Hippocrates]. PMID- 1937222 TI - [The validity of knowledge and medical ethics: historical connections from Hippocrates to Auschwitz and thereafter]. PMID- 1937223 TI - [Ventricular premature complexes--should they be treated?]. PMID- 1937224 TI - [Can we use information from the Nazi experiments?]. PMID- 1937226 TI - [The Wolf Foundation Prizes]. PMID- 1937225 TI - [The aging heart]. PMID- 1937227 TI - [Magnetoencephalography]. PMID- 1937228 TI - [Pitfalls in international comparisons of health data and indices]. AB - Comparison of published data and health indices from different countries with different health systems is subject to many pitfalls. Comparison of national expenditure for health care based on purchasing power of the currency may be misleading if the purchasing power of the health services is ignored. Comparisons may also be misleading if they ignore national geographic and demographic structures. Government and health authorities often quote different sets of data and use different terminology and definitions. This article stresses the disparity in the definition of medical manpower and points out differences relating to ratios of manpower to population and to per capita spending. Also addressed is the importance of the qualitative and value aspects of health systems not usually involved in comparison of international health indices. In conclusion, safety measures and precautions such as choosing the right index for the right purpose, adjustment of indices to the purchasing power parity of health, demographics, etc., should be used when conducting health care analyses. PMID- 1937229 TI - [Morbidity among kibbutz children determined by health interview]. AB - Morbidity in 1,565 children up to the age of 6 years on 28 kibbutzim over a period of 6 days was examined. The data reported in a health interview were compared with those reported to the kibbutz clinics. The health interview gave a morbidity of 38% during the 6 days studied, equivalent to a mean of 23.1 episodes per child per year. Of these sick children, 300 were reported as having visited the clinic, compared with 240 actually recorded as having symptoms/complaints, or 9.3 events per child per year. Nearly all of the morbidity (95%) fell into 4 major categories: respiratory, nervous system and sensory infections and digestive diseases. As reported in the health interview, the clinic was visited in 50% of the episodes; the frequency and types of diseases reported were similar for both the clinic records and the health interviews. The most clinic visits were for acute infectious diseases (100%); the least for chronic diseases (none). According to the health interview, 62% of those visiting the clinic were referred to a physician and 38% to a nurse. The corresponding percentages from the clinic records were 60 and 40, respectively. In general, the relative distribution by disease categories was similar in both health interviews and clinic records. The only significant differences were for respiratory diseases, in which a higher incidence was reported in the health interview. In the matching test between health interviews and records of clinic visits, only partial matching was found. There was 34% corroboration of dates of visit according to the health interview compared with the clinic records. With regard to diagnoses, the rate of match was only 29%. PMID- 1937230 TI - [Ultrasonic estimation of fetal weight]. AB - To generate formulas to estimate fetal weight on the basis of sonographic measurements, 226 pregnant women were scanned within 3 days of delivery. Measurements included: biparietal diameter, head circumference and area, abdominal circumference and area, and femoral length. The contribution of each parameter to the estimation of fetal weight was tested by stepwise regression analysis. The best dependent variable was found to be the log of weight. The formula based on cranial and abdominal parameters proved to be inaccurate, especially when fetal weight was less than 2500 g. The addition of femoral length improved weight estimation, with a multiple r of 0.95174. The addition of gestational age led to even more accurate formulas. The most accurate found was based on biparietal diameter, abdominal circumference, femoral length and gestational age, with a multiple r of 0.95651 and an absolute mean error of 7.976 +/- 5.657%. It also produced better weight estimates at the 2 extremes of fetal weight. PMID- 1937231 TI - [Diabetic hand syndrome in juvenile diabetes]. AB - Patients with Type I diabetes may develop a scleroderma-like syndrome, including limitation of joint mobility. This syndrome, cherioarthropathy, is considered a complication of diabetes, but its cause is unknown. We examined 30 Jewish and 13 Arab patients in our juvenile diabetes clinic for skin and joint involvement. Signs of cherioarthropathy in both hands were found in 13 children (30.2%); all had skin changes and 6 (13.5%) also had articular involvement of the hands. There was no correlation between the presence of cherioarthropathy and the patient's age or the duration of diabetes. The syndrome was significantly more frequent among Arabs (8/15, 61.5%) than Jewish children (5/30, 16.6%), p less than 0.01. There was a indirect correlation between incidence of cherioarthropathy and adequacy of glycemic control, but no difference in glycemic control between Arab and Jewish children. This may indicate a genetic factor in the development of cherioarthropathy in juvenile diabetes. PMID- 1937232 TI - [Potassium permanganate poisoning in infancy]. AB - Potassium permanganate intoxication in 3 infant girls (2.5, 2.5 and 5 months old, respectively) is described. In 2 the toxic solution was mistaken for a vitamin A+D preparation due to package similarity. The main clinical symptoms included restlessness, low grade fever and inflamed oral mucosa with black-brown discoloration. There was leukocytosis with a shift to the left. Complications described by others, such as hepatic and renal damage, upper air-way obstruction, gastrointestinal ulceration, bleeding tendency, methemoglobinemia and hemolysis, were not seen in our infants. Management included hemodynamic and respiratory monitoring, oral and gastric water lavage and milk ingestion. Laboratory follow up included CBC and hepatic and renal function tests. There were no complications, and follow-up revealed no residual abnormalities. PMID- 1937233 TI - [Clinical aspects of the antiphospholipid antibody syndrome]. PMID- 1937234 TI - [Control of myopia progression]. PMID- 1937235 TI - [Bacteremia associated with gastrointestinal endoscopic procedures. Incidence, significance and indication for antibiotic prophylaxis]. PMID- 1937236 TI - [Primary aldosteronism]. PMID- 1937237 TI - [Halogenated anesthetic agents and the liver]. PMID- 1937238 TI - [Is childhood asthma and its complications also increasing in Israel?]. PMID- 1937239 TI - [Pulmonary involvement in Behcet's disease]. PMID- 1937240 TI - [Human diseases caused by parvovirus B 19]. PMID- 1937242 TI - [Harefuah and geriatrics]. PMID- 1937241 TI - [Is Harefuah advancing in the spirit of the times?]. PMID- 1937243 TI - [Hepatitis viruses: molecular aspects with clinical implications]. PMID- 1937244 TI - [Identification of the cystic fibrosis gene]. PMID- 1937245 TI - [Is the incidence of schizophrenia decreasing?]. PMID- 1937246 TI - [The irritable bowel: a pathological or a psychological syndrome?]. PMID- 1937247 TI - [IUD-associated abdominopelvic actinomycosis]. AB - Abdominopelvic actinomycosis associated with the use of an intrauterine contraceptive device (IUD) is described. The diagnosis is usually made after exploratory laparotomy for severe abdominal pain and signs of an acute abdomen, or for prolonged lower abdominal pain and findings consistent with pelvic malignancy. 3 women aged 33, 44 and 52 years, respectively, are presented. PMID- 1937248 TI - [Blunt neck trauma]. AB - Blunt neck trauma is usually caused by auto accidents and may result in various degrees of laryngeal injury. Treatment involves careful monitoring followed by surgical intervention when there is deterioration, or by early exploration and laryngeal fixation (internal or external). 16 patients treated for blunt neck trauma, ranging in age from 10-54 years (mean 27.7), were studied. Only 1 required surgical intervention. PMID- 1937249 TI - [A new method of treating encopresis]. AB - The treatment program described was designed to establish regular, normal toilet habits in children suffering from disturbances of defecation, including chronic constipation, frequent soiling and refusal to sit on the toilet. 17 children, aged 2.5-6 years were referred during 1988. 1 had a prolapsed rectum while the other 16 had no physiological anomaly but exhibited general negativism in addition to their bowel problems. They were treated with operant conditioning techniques combined with the use of glycerine suppositories. The use of suppositories lasted an average of 1 week (range 1-35 days). The suppositories served as a discriminative stimulus for defecation, ensured daily rectal evacuation under controlled conditions, and allowed the therapist to control timing of bowel movements. Control of timing is necessary so that the therapist can correct dysfunctional defecation directly by shaping and positively reinforcing appropriate toilet behavior, and by eliminating fearful and oppositional responses. Treatment was successful in all and there were no relapses. For most of the children there was also general behavioral improvement. PMID- 1937250 TI - [Nerve injuries in bicycle riders]. AB - 2 cases of damage to peripheral nerves following bicycle riding are described in males aged 13 and 35 years, respectively. In 1 there was injury to the ulnar nerve at the level of the wrist, with hypesthesia of the 2 ulnar digits and paresis of intrinsic muscles. In the other case there was involvement of the pudendal nerves with numbness of the buttocks and genitalia, and with difficulty in achieving erection. After cycling was stopped for a few weeks the symptoms disappeared spontaneously, with full recovery. Once symptoms subside completely cycling can be resumed, although with certain precautions. PMID- 1937251 TI - [Congenital granular cell epulis]. AB - Congenital granular cell epulis is an uncommon pedunculated tumor of the upper alveolar mucosa found only in newborns. The lesion is not usually associated with other congenital deformities, but presents a major esthetic problem and interferes with nursing. We present a case of a double epulis, 7 cm in diameter, in a 2-day-old girl. Treatment is simple excision, and no recurrences have been reported. The lesion must be differentiated from granular cell myoblastoma. PMID- 1937252 TI - [Lung transplantation--state of the art]. PMID- 1937253 TI - [Fetal Doppler echocardiography]. PMID- 1937255 TI - [Quality assurance in medicine: the next decade]. PMID- 1937254 TI - [Management of prematurely ruptured membranes at term]. PMID- 1937256 TI - [Spongiform encephalopathies caused by slow viruses from the inorganic world?]. PMID- 1937257 TI - [Effect of physical exercise on insulin action and glucose homeostasis]. PMID- 1937259 TI - [Gastric acid secretion: physiological mechanisms and clinical applications]. PMID- 1937258 TI - [Sepsis, fibronectin and the reticuloendothelial system]. PMID- 1937260 TI - [Etiology and surgery of varicose veins of the lower limb]. PMID- 1937261 TI - [Advances in therapy of asthma]. PMID- 1937262 TI - [Bias in medical research]. PMID- 1937263 TI - [Pulmonary hypertension in a patient with lupus erythematosus]. PMID- 1937264 TI - NEHW embraces Healthy People 2000. PMID- 1937265 TI - Heat stress continues to affect workers. PMID- 1937266 TI - Hepatitis B: are you at risk? What you can do to protect yourself: an education project for student nurses. PMID- 1937267 TI - EMF primer. PMID- 1937268 TI - Differentiation of species of Eimeria from the fowl using a computerized image analysis system. AB - Oocysts of Eimeria species from the fowl have been identified using a computerized image-analysis system (Leitz T.A.S. Plus Image-Analyser). The system enabled semiautomatic measurement of oocyst dimensions with subsequent species of diagnosis based on graphic statistical evaluation of size and shape of measured parasites. E. mitis, E. acervulina, E. brunetti, E. maxima, E. tenella and complex of E. necatrix and E. praecox were distinguishable both in pure cultures and in mixtures. It was not possible to distinguish E. praecox from E. necatrix using this system. PMID- 1937269 TI - Predation of ticks of the Rhipicephalus sanguineus (Latreille, 1806) group and Boophilus microplus (Canestrini, 1888) (Acari: Ixodidae) by Nothura Temminck, 1815 (Aves: Tinamidae) in Salta, Argentina. PMID- 1937270 TI - Experimental verification of the effect of constant and changing water temperature on the micropopulation growth in Gyrodactylus gobiensis Glaser, 1974 (Monogenea) parasitizing gudgeon (Gobio gobio L.). AB - It has been verified under laboratory conditions that constant and changing water temperature markedly affects the micropopulation growth in Gyrodactylus gobiensis parasite on the body surface of gudgeons (Gobio gobio L.). At a water temperature of 12 degrees C, the number of gyrodactylids gradually increased up to the mean value of 63 specimens per host, which was reached on days 27-28 after experimental infection. At a constant temperature of 18 degrees C, the parasites completely disappeared from the bodies of infected fishes on days 15-20 p.i. A similar effect was produced by gradually increasing temperature from 12 to 18 degrees C, while the decrease in water temperature from 18 to 12 degrees C resulted in an increase in the parasite number. PMID- 1937271 TI - On the dissemination of two Far East monogenean parasites (Dactylogyrus achmerovi Gussev, 1955 and Gyrodactylus kherulensis Ergens, 1974, of carp (Cyprinus carpio L.)) in Czechoslovakia. PMID- 1937272 TI - Early development of Khawia sinensis Hsu, 1935 (Cestoda: Caryophyllidea), a carp parasite. AB - The development of the tapeworm Khawia sinensis parasitizing carp (Cyprinus carpio L.) has been studied from the release of cestode eggs into water to the formation of infective procercoids in the intermediate host under laboratory conditions. The rate of embryonal development is greatly influenced by the water temperature. While at 5 degrees C the development of oncospheres was not recorded, at 10-12 degrees C, 15 degrees C, 20-22 degrees C, and 23-24 degrees C oncospheres were fully formed after 57, 42, 21 and 16 days, respectively. Infectivity of oncospheres was confirmed by successful experimental infection of the intermediate hosts: Tubifex tubifex and Limnodrilus udekemiamus (Oligochaeta: Tubificidae). Fully formed procercoids infective for the definitive host were found in the intermediate host from 52 days of development at 20-22 degrees C. From the third week of development in the intermediate host, most of the parasite larvae were located in the anterior part of the tubificid body, mainly between 8th and 15th segments. PMID- 1937273 TI - The life cycle of Echinostoma bolschewense (Kotova, 1939) (Trematoda: Echinostomatidae). AB - The life cycle of E. bolschewense, the species with 37 collar spines and closely related to E. revolutum, was experimentally studied. The following developmental stages are described: mother and daughter rediae, cercaria, metacercaria, and adult. The freshwater prosobranchiate snail Viviparus contectus was found to be the first intermediate host in nature. Under experimental conditions, the miracidia developed in V. contectus. They did not, however, penetrate into Bithynia tentaculata or into any of the pulmonate snails tested. The cercariae encysted in various Prosobranchia and Pulmonata. Adult worms were commonly obtained from hamsters (Mesocricetus auratus) and only exceptionally from chickens (Gallus gallus f. dom.). The species studied is considered to be conspecific with Cercaria bolschewensis described by Kotova (1939). PMID- 1937274 TI - Systematic status of Thominx platyrrhinorum Barus, 1961 (Nematoda: Capillariidae). AB - A reexamination of the type specimens of Thominx platyrrhinorum Barus, 1961, described from the small intestine of the monkey Cebus capucinus from a zoo in Czechoslovakia, has revealed that it belongs to the genus Aonchotheca Lopez Neyra, 1947. The minute refractile formations on the surface of the proximal part of the spicular sheath, originally described as spines in this species, are also present in Aonchotheca annulosa parasitizing murid rodents. Since there are no substantial morphological or biometrical differences between these two species, as indicated by the description of A. annulosa specimens originating from Apodemus sp. from Czechoslovakia, T. platyrrhinorum is considered to be a synonym of A. annulosa (Dujardin, 1845). Another synonym of the latter is the species originally described as Thominx sadovskoi (sic) (= sadovskajae) Morozov in Skryabin et al. 1957. Armocapillaria Gagarin et Nazarova, 1966, earlier considered a synonym of Pterothominx Freitas, 1959, is now reerected as a subgenus of Aonchotheca Lopez-Neyra, 1947. Armocapillaria moschiferi and Capillaria brochieri are transferred to Aonchotheca as A. (A.) moschiferi (Gagarin et Nazarova, 1966) comb. n. and A. (A.) brochieri (Justine, 1988) comb. n. PMID- 1937276 TI - Ultrastructure of the digestive tract of Echinostoma revolutum cercaria. AB - The digestive tract of a fully formed free-swimming cercaria of Echinostoma revolutum (Froelich, 1802) Dietz, 1909 was studied by electron microscopy. The oral sucker and pharynx are covered by a tegument. The oesophagus and the caeca are not luminized. They are packed with giant epithelial cells with electron dense granules of irregular shape, rough endoplasmic reticulum and its cisterns, and Golgi apparatus. The tegument of the oral sucker cavity contains numerous uniciliate receptors. PMID- 1937275 TI - Observations on some nematodes parasitic in freshwater fishes in Laos. AB - In 1989, samples of some freshwater fishes collected in Vientiane Province (R. Mekong basin) in Laos were examined for helminths. This material comprised 11 species of parasitic nematodes (7 adults and 4 larvae), including 3 species new to science: Camallanus (Camallanus) hampalae sp. n. from Hampala macrolepidota, Procamallanus (Punctocamallanus) punctatus sp. n. from Mystus rhegma and Mystus sp., and Rhabdochona (Globochona) equispiculata sp. n. from Hampala macrolepidota and H. dispar. Zeylanema Yeh, 1960 is considered a subgenus of the genus Camallanus, Dentocamallanus subgen. n. (type species C. (D.) sweeti (Moorthy, 1937)) is proposed for the species of Paracamallanus with teeth in the buccal capsule, and Punctocamallanus subgen. n. (type species P. (P.) punctatus sp. n.) for the species of Procamallanus with the buccal capsule ornamented with punctations. The name Rhabdochona wangi nom. nov. is proposed for R. bagarii Wang et Guo, 1983 (a homonym to R. bagarii Gupta et Srivastava, 1982) and Camallanus gomtii Gupta et Verma, 1978 is newly synonymized with Neocamallanus ophiocephali (Pearse, 1933). All the nematodes are recorded from Laos for the first time. The parasites are briefly described and illustrated and some problems concerning their taxonomy and geographical distribution are discussed. PMID- 1937277 TI - Description of Spinicauda dugesii sp. n. (Nematoda: Heterakidae) of Podarcis dugesii (Reptilia: Lacertidae) from Madeira Island. AB - Spinicauda dugesii sp. n. (Heterakoidea, Heterakidae), parasite of the gut of the lizard Podarcis dugesii Milne-Edwards, 1829 (Reptilia, Lacertidae) from Madeira Island is described. Males of the new species are characterized by their narrow lateral alae, and curved and very chitinized spicules of the same length: females by their thick-shelled, almost round and embryonated eggs. At the external wall of the host's gut, parasitic cysts of this nematode with immature stages inside were also observed. PMID- 1937278 TI - In vivo response of multi-resistant Plasmodium falciparum infections to mefloquine and its combination with sulfadoxine/pyrimethamine in Cambodia. PMID- 1937279 TI - Finding of the coccidium Eimeria ferrisi levine et Ivens, 1965 (Eimeriidae, Apicomplexa) in feral house mice (Mus musculus) in South Bohemia. PMID- 1937280 TI - The chemotherapy of monogeneans which parasitize fish: a review. AB - Monogeneans which parasitize fish are still treated by bathing the fish in solutions of simple chemicals or staining dyes. In the early 1960s an insecticide, trichlorphon, replaced to a large extent the formerly used simple chemicals. Its success was greater specificity against monogeneans and other ectoparasites, and to its great tolerance by the fish. The fact that the number of important monogenean species (i.e. Pseudodactylogyrus anguillae, P. bini, Gyrodactylus salaris) which cannot be treated sufficiently with simple chemicals or even trichlorphon is increasing, led to the need for systemically acting, novel chemotherapeutics. In laboratory and small scale trials praziquantel, levamisole, mebendazole and toltrazuril have been tested for efficacy against a broad spectrum of monogenean species. PMID- 1937281 TI - Synergistic effects of kinship, sex and rank in the behavioural interactions of captive stump-tailed macaques. AB - In almost all non-human primate species kinship, sex and rank bias the patterning of interactions among subjects, seemingly in a way that favours the individual's fitness. A number of studies have been done in order to study separately the effects of these variables, concluding that an adequate model of interactions cannot be developed assuming preponderance of a single variable. The 'willingness' of one animal to interact with another can be explained as the result of assessing the possible outcomes (proximate and/or ultimate) of the interaction. The interrelationship of variables such as kinship, sex and rank, among others, provides the actors with a basis for deciding their rates of social interactions. The following study was done to assess whether kinship, rank and sex exerted independent, additive effects in the within-group distributions of eight social behaviour categories of captive groups of stump-tailed macaques. We found that the three variables synergistically affected the patterning of all behavioural categories. This suggests that the pay-offs of social interactions do not vary linearly, being intrinsically correlated with the actors' attributes so that uncertainty in the choice of a potential partner is minimized. PMID- 1937282 TI - Is lipsmacking an indicator of social status in baboons? AB - Lipsmacking is performed by many Old World monkey species, and some studies of baboons and macaques suggest that lipsmacking may be associated with social status. We studied 60 adult anubis baboons (Papio cynocephalus anubis) for 18 months, measured social status and the rate of lipsmacking, and used these data to test the hypothesis that lipsmacking is related to social status. Our results indicate that social status and lipsmacking were not significantly correlated for either males or females. Analysis of lipsmacking in relation to social class (high vs. low) showed no significant difference between status classes for either sex. Lipsmacking was, however, found to be positively associated with affinitive behaviors. These results suggest that baboon lipsmacking provides positive social communication independently of social status. PMID- 1937284 TI - Influence of context on mounting and presenting among mature male Japanese macaques. PMID- 1937283 TI - Male mating behaviour and paternity discrimination by DNA fingerprinting in a Japanese macaque group. PMID- 1937285 TI - Birth season shifts to a 13-month pattern in squirrel monkey groups kept indoors for 7-12 years. PMID- 1937286 TI - Independent digit control in foraging by the aye-aye (Daubentonia madagascariensis). PMID- 1937287 TI - Szalatavus attricuspis, an early platyrrhine primate. PMID- 1937288 TI - Carcinogenicity study of cochineal in B6C3F1 mice. AB - The carcinogenicity of cochineal, a red colouring used in food and other products, was studied in a 2-yr bioassay in B6C3F1 mice. Groups of 50-55 mice of each sex were given 0, 3 or 6% cochineal in the diet for 2 yr. Mice of all groups developed tumours including hepatocellular adenomas or carcinomas, pulmonary adenomas or adenocarcinomas and lymphomas or lymphatic leukaemias, and the incidences of these tumours were not significantly different in treated and control groups. The results indicate that cochineal lacks carcinogenicity in mice and are consistent with those of in vitro short-term assays of cochineal and of carminic acid, an active principle of cochineal. PMID- 1937289 TI - Long-term toxicity/carcinogenicity study of calcium lactate in F344 rats. AB - The long-term toxicity/carcinogenicity of calcium lactate, a food additive, was examined in F344 rats. Calcium lactate was given ad lib. in the drinking-water at levels of 0, 2.5 or 5% to groups of 50 male and 50 female rats for two years. No clear toxic lesion was specifically caused by long-term administration of calcium lactate. No significant dose-related increase was found in the incidences of tumours in any organ or tissue. The results indicated that calcium lactate had neither toxic nor carcinogenic activity in F344 rats. PMID- 1937290 TI - Effects of a synthetic retinoid, etretinate (RO 10-9359), on the peripheral metabolism of thyroid hormones in rats. AB - Male Wistar rats were administered a synthetic vitamin A compound, etretinate, at various doses, including levels exceeding recommended therapeutic doses. At 2 mg/kg body weight/day given intragastrically, no effects were detected with respect to serum retinol or thyroid hormones after 15 days of treatment. At 5 mg/kg/day only a slight decrease in serum triiodothyronine was detected. In contrast, the dose of 20 mg/kg/day for 15 days resulted in relatively severe effects: body weight was decreased by 23% in comparison with the controls, serum retinol was decreased by 62% (while liver stores of vitamin A were unaffected), and serum thyroxine and triiodothyronine levels were, respectively, 24 and 29% lower than in the controls. A kinetic study demonstrated that the biological half life of serum thyroxine decreased by 62% and that of serum triiodothyronine by 24%, suggesting increased peripheral metabolism of the thyroid hormones. The two main metabolic pathways (i.e. hepatic 5'-monodeiodination and glucuronide conjugation) were not significantly affected by etretinate treatment and do not account for the apparent metabolic loss of the thyroid hormones. This experiment demonstrates that etretinate doses beyond the therapeutic range are required to imbalance thyroid hormone homoeostasis. Possible mechanisms relating to increased hormonal clearance in rats treated with high doses of etretinate are discussed. PMID- 1937291 TI - Transformation of mammalian cells by luteoskyrin. AB - The transforming activity of luteoskyrin (LS), a bis-anthraquinoid mycotoxin produced by Penicillium islandicum Sopp., and a hepatocarcinogen in rodents, was examined by an in vitro transformation assay using mouse embryonal Balb/3T3 A31-1 1 cells. The results revealed that LS induced type III foci at 0.5 micrograms/ml, and that the cells selected from these foci by soft-agar cloning grew with a high saturation density. Thus, it was confirmed that LS not only induces hepatic tumours in laboratory animals, but also transforms in vitro cultured mammalian cells. The tumorigenicity of the transformants obtained was confirmed by transplantation into nude mice and by image analysis with IIIIn. A transfection assay, using calcium phosphate co-precipitation, demonstrated that the DNA of the cloned cells transformed NIH3T3 cells. Northern blot also revealed transcriptional activation of c-myc and c-Ha-ras oncogenes. The possible participation of LS-derived hydroxy radicals in the formation of genetic lesions was discussed. PMID- 1937292 TI - Modulation of low-density lipoprotein-induced inhibition of intercellular communication by antioxidants and high-density lipoproteins. AB - In order to study the capacity of antioxidants and high-density lipoproteins (HDL) to modulate the effects of low-density lipoprotein (LDL) on intercellular communication, arterial smooth muscle cells and a dye transfer method were used. LDL, in contrast to HDL, inhibited the communication between arterial smooth muscle cells from human umbilical cord and thoracic aorta in a dose-dependent manner. LDL, which can be oxidized, as detected by the lipid-peroxidation assay and gel electrophoresis, did not influence cell-cell communication in the presence of the antioxidants butylated hydroxytoluene (BHT), alpha-tocopherol and glutathione. The results suggest that LDL must undergo oxidative modification before it can influence intercellular communication. Like antioxidants, HDL diminished the LDL-induced inhibition of cell-cell communication. This study suggests that the modulation of gap-junctional communication by the balance of HDL and LDL in plasma may influence atherogenesis. PMID- 1937293 TI - Studies on the effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on the rodent forestomach. AB - A novel class of hypocholesterolaemic agents, HMG CoA reductase inhibitors, was shown to cause mucosal thickening in the rodent (mouse and rat) forestomach after subacute/subchronic oral administration. These changes were characterized histologically by acanthosis and hyperkeratosis of the squamous epithelium with submucosal oedema and occasionally cellular infiltration. This drug-induced hyperplastic response was both dose and time dependent, did not occur after subcutaneous administration, and was confined entirely to the rodent forestomach (not observed in any other area of the gastro-intestinal tract). The forestomach hyperplastic response correlated with the pharmacological potency of HMG CoA reductase inhibitors of similar structure (observed to varying degrees with all HMG CoA reductase inhibitors examined to date). PMID- 1937294 TI - A teratogenic study of carbaryl in Swiss albino mice. AB - To study the teratogenicity of carbaryl, groups of 10 pregnant mice were dosed, by gavage, with 0, 100, 150 or 200 mg carbaryl/kg body weight, in corn oil, on day 8 or day 12 of pregnancy or daily (as daily doses) from day 6 to day 15. The two higher doses were toxic to both dams and foetuses regardless of the timing of treatment. Treated dams generally showed reduced weight gains but total weight gain was significantly reduced only for dams given 200 mg carbaryl on day 8 or day 12 of gestation. Maternal mortality was increased in most groups given 150 or 200 mg carbaryl. Carbaryl treatment tended to reduce litter size, to increase the percentage of resorbed foetuses, and to reduce foetal weight. There were increased incidences of open eye, of certain visceral abnormalities, and of reduced ossification in virtually all treated groups. The variety of abnormalities in treated foetuses reflected the dysmorphogenic potential of the pesticide. More aberrations were seen in foetuses from dams treated throughout organogenesis than in those from dams given a single dose. PMID- 1937295 TI - Strain differences in the effect of mercury on murine cell-mediated immune reactions. AB - The effect of mercuric chloride on mitogen-induced DNA synthesis was investigated using lymphocytes from SJL and DBA mice, which are known to be susceptible and resistant to induction of autoimmunity by mercury, respectively. Treatment of SJL mice with 5 ppm mercuric chloride in their drinking-water for 2 wk resulted in a two- to three-fold increase of concanavalin A and lipopolysaccharide-induced thymidine incorporation in splenocytes. Mitogen-induced thymidine incorporation in splenocytes from identically treated DBA mice was not significantly different from that seen in controls. In vitro treatment of splenocytes from SJL mice with mercury caused a dose-dependent increase of concanavalin A-, lipopolysaccharide and phytohaemagglutinin-induced thymidine incorporation. This effect was optimal when 10(-7)-10(-8) M-mercuric chloride were added as a pulse 1 hr before the addition of mitogens, whereas higher and lower concentrations were less effective. The mitogen-induced DNA synthesis in splenocytes from DBA mice was either not affected by the addition of mercuric chloride or decreased by higher mercury concentrations. The addition of mercury to thymocytes from DBA and SJL mice caused a slight and moderate increase, respectively, in concanavalin A induced thymidine incorporation. PMID- 1937296 TI - Cutaneous effects of transdermal levonorgestrel. AB - The irritation of transdermal devices delivering levonorgestrel and the permeation enhancer ethyl acetate with or without ethanol was evaluated in rabbits. Erythema and oedema were assessed 24, 48 and 72 hr and 7 days after application of the 24-hr delivery system. The devices were found to be mild to moderately irritating, with erythema the primary manifestation. No differences were observed between devices using pure ethyl acetate or ethyl acetate-ethanol (7:3, v/v) as enhancers. Devices using pure ethanol as an enhancer gave levels of irritation similar to those using ethyl acetate-ethanol (7:3) or pure ethyl acetate. Control devices containing only water (no drug) were also found to be mildly irritating to rabbits following a 24-hr exposure period. A histological evaluation of the application sites of two of the formulations confirmed the visual observations of mild subacute irritation. The changes produced by transdermal levonorgestrel were reversible. The problems of skin irritation of transdermal devices is discussed with particular reference to the use of ethyl acetate and ethanol as skin penetration enhancers. PMID- 1937297 TI - [Motor activity of the point of the tongue in forming dento-alveolar consonants]. AB - Electromagnetic articulography, a new tool for the study of articulatory movements, was used for the examination of apical tongue dorsum movements during the production of repeated VCV sequences. In our study of 16 normal German speakers, the trajectories of three apicolingual consonants, /t/, /s/ and /ss/, in an aCa sequence were assessed for inclination and length of the articulatory movement trajectories. A clear differentiation in length and direction of articulatory movements for the VCV utterances/ata/, /asa/ and /ass a/ was revealed. Variation in the direction of initial movement starting from the resting position was interpreted as effect of coarticulation. PMID- 1937298 TI - A simple clinical method of evaluating perceived hypernasality. PMID- 1937299 TI - Importance of parent-child interaction in the genesis of stuttering. PMID- 1937300 TI - The tone-dynamic method in the treatment of glottal insufficiency. PMID- 1937301 TI - [Electromagnetic articulography: a new method for studying the motor function of the velum palatinum]. AB - The observation of articulatory movements, particularly of velar movements, is of considerable theoretical and practical interest in evaluating the velopharyngeal function of the cleft palate patient. A new electromagnetic device is presented for tracking the movements of the velum and the tongue simultaneously in correlation with the posterior pharyngeal wall and the hard palate in the midsagittal plane. An inductive measuring principle is used; a miniature transmitting coil is placed at the lower margin of the velum, another coil is used for recording the position of the posterior pharyngeal wall as well as the surface of the hard palate and the movements of the tongue dorsum. The measuring principle is described and the movements of the velum during speech production are demonstrated in cleft palate patients with different speech results. PMID- 1937302 TI - Study on the microstructures of skull fracture. AB - The authors observed the edges of skull fractures under the scanning electron microscope. Many microfractures can be found along the main fracture lines. The width of the microfractures varies from 5 to 100 microns. They may be located either in the external compact bone or between the outer compact bone and diploe, or in the diploe. Those within the diploe form transverse, longitudinal or spiral fractures of bony trabeculae. Collagenous fibre bunches in the bony matrix may be divided or broken and the different layers of collagenous fibre may be separated. The blood vessels inside the skull may be crosscut or longitudinally torn by the fracture lines. Sometimes the torn blood vessels may be drawn out of the Haversian canals. In antemortem fractures, the fibrin networks and red blood cells can be easily found in the depths of those cracks. The possible mechanism of formation of the microfractures and the possibility of differentiation between ante- and post-mortem fractures are discussed. PMID- 1937303 TI - beta-Phenethylamine causes false positive amphetamines in post mortem specimens when tested by SYVA EMIT. PMID- 1937304 TI - Urinary cannabinoid analysis: comparison of four immunoassays with gas chromatography-mass spectrometry. AB - Eight-eight urine samples were analysed by the EMIT d.a.u. Cannabinoid 20 ng homogeneous enzyme immunoassay, the DPC cannabinoid radioimmunoassay, two in house cannabinoid radioimmunoassays and a gas chromatography-mass spectrometry method for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol. There was good qualitative agreement between the methods with few discrepancies in the borderline region. PMID- 1937305 TI - Family violence and Asian drinkers. AB - This is a study of 70 consecutive referrals to the Department of Psychological Medicine, National University Hospital, for treatment of drinking problems. There were 31 Chinese and 39 Indian drinkers, with 63 males and 7 females. Family violence with physical abuse occurred in 21 cases (30%). One of three wives of drinkers had been physically abused, but no children were victims. Drinkers with family violence were generally younger and more severely dependent on alcohol than the non-violent drinkers. There was no relationship between family violence and the ethnicity or marital status of the drinkers. PMID- 1937306 TI - Comparative analysis of illicit heroin samples. AB - The comparative analysis of street heroin samples is still an object of scientific discussion. A combination of a wide range of analytical techniques is necessary to obtain a valid amount of information about the sample composition, and it is impossible to define an unique analytical approach. We suggest a complete analytical sequence based on analysis of volatile compounds, opiates, diluents, adulterants and metals, by head space gas chromatography (HS/GC), gas chromatography mass spectrometry (GC/MS), thin layer chromatography (TLC), high pressure liquid chromatography (HPLC) and atomic absorption (AA) using a sample amount as low as 50-100 mg. The outlined procedure can be successfully applied to routine work, thus obtaining suitable information about a sample's chemical composition. This helps to attribute or exclude common sources of separate specimens. Results obtained on 33 street heroin samples confiscated in the metropolitan area of Rome are listed. PMID- 1937307 TI - Variation of the amide I and amide II peak absorbance ratio in human hair as measured by Fourier transform infrared spectroscopy. AB - Human scalp hair samples were examined by Fourier transform infrared spectroscopy and the ratio of the amide I to amide II band absorbances was determined. The effects of hair oxidation, color, age of sample, and sex of source were examined. Scalp hair from 98 individuals was also analyzed. While there were differences in the amide absorption band ratios, these were difficult to relate to the individualization of the hair samples and did not appear to have a sufficient discriminatory value for routine forensic use. PMID- 1937308 TI - Magnesium, calcium and zinc fluctuations on skin induced injuries in correlation with time of induction. AB - In the present study, fluctuations of trace elements Mg, Ca and Zn concentrations with time on skin-induced injuries was investigated. To accomplish this, 144 animals (pig) aged between 5-6 months scheduled for food provision process (slaughter) were used. At the gluteus area, injuries were induced prior to slaughter at intervals of 30 s, 30 min, 1, 2, 4, 8 h. Local anaesthesia and cold therapy for prompt relief of pain (ethylchloride, C2H5Cl) was applied. Postmortem tissue excision in and around the injured site was promptly performed. The tissue obtained was segmented into three zones of equal distances (2 cm) in between and weighed 3 g wet weight. Tissue specimens were analysed by atomic absorption spectroscopy for the three elements. The results were correlated with time of injury. Suggestive alterations in trace elements mean concentrations with time were confirmed. The ratios of the mean in twos (Ca/Zn, Ca/Mg, Mg/Zn) versus time were graphed. Effectively, the curves achieved by analysing postmortem tissues, serve to estimate the time of an injury induced in vivo. PMID- 1937309 TI - Investigations into the analysis of the rate of decay of the compound action potentials recorded from the rat sciatic nerve after death: significance for the prediction of the post-mortem period. AB - There have been a number of papers that have reported the investigations of electrical stimulation of muscle groups in order to determine the post-mortem period. To the authors knowledge, no techniques have been described that analyse the compound action potentials (CAP) of various nerve fibre groups after death. This paper reports the monitoring of both the amplitude and latency changes of the CAP recorded from a stimulated rat sciatic nerve after death. Initial results suggest that the method my be useful in determining the early post-mortem period within 1 or 2 h after death. It may also be of use in measuring nerve conduction delay in various pathological conditions that can affect the neural network; for example diabetes. PMID- 1937310 TI - Analysis of the possible use of liquid crystals in fingerprinting. AB - Preliminary results concerning the use of liquid crystals (LC) in fingerprinting are given. These were based on thin layers of liquid crystals, changing colours (observed in linear polarized light) due to dissolved organic matter, transferred from fingers' surfaces. The possibility is shown of using LC to illustrate not only the surface but also the spacial configuration of a fingerprint. Relations are given between the amount of organic matter generating a fingerprint on a given surface and the coloured "response" of LC which may be used for identification as well as approximate estimation of the process of ageing. PMID- 1937311 TI - Application of a computer assisted image analyzer to the assessment of area and number of sites of dental attrition and its use for age estimation. AB - A simple method was devised to assess dental attrition in terms of its area and number of sites by using dental plaster casts and a computer assisted image analyser. The changes presented on the occlusal surfaces of teeth were investigated for age estimation using these criteria. The area of attrition on each tooth demonstrated a significant positive correlation with age, but a wide individual variation was observed in the values for each tooth. Therefore, this method was unsuitable for accurate age estimation of a single tooth. A strong negative correlation with age was observed in the number of sites of attrition. A multiple stepwise regression analysis using the variables 'attrition area' and 'attrition number' revealed multiple correlation coefficient values of 0.93. The quantitative assessment of both horizontal and vertical factors of dental attrition would be essential to improve the accuracy of this method. PMID- 1937313 TI - Carbazole alkaloids. III. PMID- 1937312 TI - The bryostatins. PMID- 1937315 TI - [The modification of the mechanically loaded periodontium during orthodontically induced tooth movement with nonsteroidal anti-inflammatory agents in an animal experiment]. AB - In a total of 123 female adult Wistar rats the first upper molar was moved by orthodontics for more than 28 days. This orthodontically stimulated tooth movement was influenced by local application of Cu-salicylate, Cu-indomethacin or epsilon-Aminocapronacid. The application of Cu-salicylate and Cu-indomethacin caused reduced tooth movement, a decrease in osteoclasts in the pressure region of the periodontium, and an increase of hydroxyproline in the desmodont. Generally, the local application of Cu-nonsteroidal antiphlogistics seems to stabilize the experimentally induced tooth movement. PMID- 1937314 TI - [The causes of and repair procedures in external root resorption following palatal suture expansion with magnetic and conventional dilators. Experimental animal research on Macaca fascicularis monkeys]. AB - Eight Macaca fascicularis monkeys received rapid maxillary expansion with conventional and magnetic appliances. The histomorphometric analysis (SEM) showed increased external root resorption (ERR) in: multirooted teeth, buccal root surfaces, mesiobuccal roots and apical zones. ERR is determined by the impulse, the decrease in the periodontal width and the extent of mineralization of adjacent hard tissues. The microscopic examinations of light, UV and SEM defined two types of cellular cement in ERR areas: a) unfunctional repair cement (slow type), b) functional repair cement (rapid type). The first was characterized by the absence of Sharpey's fibers and by overlapped incremental lines, the second by the formation of new Sharpey's fibers and discriminated incremental lines. These incremental lines indicate five sequential phases with diverse rates of cement apposition, i.e. lag-, incipient-, peak-, steady-, and retreating phase. Therefore, the study recommends the application of a fixed retainer immediately subsequent to rapid maxillary expansion which is followed by an intermittent retention appliance. PMID- 1937316 TI - [Schmuth's group findings--a simple system for classifying dysgnathias]. AB - The advantages and disadvantages of Schmuth's findings, which classify eugnathic as well as dysgnathic dentition are opposed to Angle's classification. Using Schmuth's findings is a way of classifying without ignoring the physiological variability in the area of the first molars, which can lead to false diagnosis. 386 models were examined at the beginning of the patients' treatment. The results are discussed. PMID- 1937317 TI - [3-dimensional computer-supported model and hologram evaluations]. AB - For the three-dimensional measurement of plaster casts and holograms a self fabricated measurement device will be introduced. This measurement device has the following specialties: 1. All measurements will be done without any subsidiary optical instruments like spectacles, microscope, binoculars or any thing else. Therefore a tire of measuring can be carried out. 2. Only two 3 mm deep holes should be ground in the base of the plaster casts as preparatory measures for the three-dimensional measurements of the plaster casts. 3. The menu- and window orientated software gives the possibility for the collecting of data in a data bank. 4. The precision of these measurement results, even in the case of measuring holograms, are frequently better than the common way of measuring plaster casts. 5. The precision and information by the holograms are nearly the same, compared with the common plaster casts. 6. The tracing and measuring of the angles and lines by this newly measurement device guarantees the doctor a quick overview concerning the therapeutic measures. 7. The transfer of these data in the lateral-rays and in the posterior-anterior findings leads to a better diagnostic. That means the diagnostic horizon will be widened with this new method. PMID- 1937318 TI - [Cheilognathopalatoschisis: its classification and epidemiology]. AB - This article presents a survey of the currently used classification of primary and secondary cleft formations especially from the gentic view. In connection with frequency data a clear distinction is required for the terms: incidence, prevalence and presence. Epidemiologic data, particularly from European countries, are discussed and the conclusion drawn that the data available so far largely represents approximate values. Reliable statistic data are a prerequisite for the evaluation of effect of possible future prevention. PMID- 1937319 TI - [The osteoplastic care of the cleft jaw--an advance for the orthodontic treatment of cleft patients?]. AB - This survey deals with problems of osteoplastic supply of the cleft from the orthodontic point of view. Remarkable parallels exist between primary and secondary osteoplasty: The involution stability of the alveolar process is only presented in a space-less tooth line. Therefore, the primary goal is to guarantee tooth eruption in the former cleft area. However, the antalogous bone graft in the former cleft area has to have a similar structure as adjacent alveolar bone. If tooth germs pass through the bone graft, an own parodont can be built up in the course of eruption. This is applicable to both dentitions. Accordingly, the osteoplasty of clefts is the most important prerequisite for stable treatment results and a healthy dentition. PMID- 1937320 TI - [The adjustment of the canine teeth adjacent to the cleft depending on the time of late primary osteoplasty]. AB - Timing for secondary bone-grafting is decisive for a successful orthodontic alignment of canines, adjacent to the cleft. This could be shown after evaluation of diagnostic data from 123 patients with unilateral cleft alveolus and cleft lip and palate and in a clinical follow-up of 29 former patients, 7.3 year after treatment. Concerning eruption and periodontal conditions of cleft adjacent canines, better results could always be seen, if bone was grafted, before mineralisation of canine root has reached 3/4 of its total length. If grafting was done after this stage, disturbances in eruption occurred more frequently. Most canines tended to erupt palatally but could successfully be aligned orthodontically. The follow-up study showed good results concerning probing depth, pulp reaction and periodontal stability. Using our own clinical data, best chronologic age for bone grafting lies between 9 1/2 and ten years. PMID- 1937322 TI - [Infections caused by staphylococci. The human as a source of infection for S. aureus and coagulase negative staphylococci]. AB - Both Staphylococcus aureus and coagulase-negative staphylococci are among the most important pathogens of nosocomial infections. While Staphylococcus aureus can cause a variety of pyogenic infections and toxin-mediated diseases coagulase negative staphylococci of the Staphylococcus epidermis group play an important role in infections developing in immunocompromised patients and those with temporarily or permanently implanted foreign bodies made of polymer. The major sources of staphylococcal infections are the skin and mucosa in humans. While in the case of Staphylococcus aureus the infection route may be either endogenous or exogenous, in the case of coagulase-negative staphylococci, the endogenous route predominates. This ecological-epidemiological situation forms the basis for strategies aimed at preventing nosocomial staphylococcal infections. PMID- 1937321 TI - [Active canine tooth movement by spongiosa graft in bilateral cheilognathopalatoschisis]. AB - Bone grafting in the alveolar cleft offers a bony support in the alveolar process for the erupting canines and should be performed before the eruption of the teeth starts. Although bone grafting is done in time, the eruption of the canines does not always follow spontaneously. This is why a simultaneous ligation of the canines is sometimes indicated. The ligature can be threaded through the bone graft. Active eruption of the canines can begin eight weeks post operation. This procedure ensures a proper alignment of the canines in a well-defined processus alveolaris. The method is demonstrated in a bilateral cleft lip and palate patient. PMID- 1937323 TI - [Diagnosis of Lyme neuroborreliosis. Detection of intrathecal antibody formation]. AB - The most common neurological manifestation of Lyme disease is lymphocytic meningoradiculitis (Banwarth's syndrome, stage II). In rare cases, chronic progressive encephalomyelitis (stage III) with symptoms similar to multiple sclerosis is observed. Antibodies against Borrelia burgdorferi are detectable in 70-90% of stage II cases, with IgM-antibodies predominating in the first two weeks, and IgG-antibodies thereafter. Detection of specific intrathecal antibodies is the best serodiagnostic parameter for diagnosing neuroborreliosis. With the aid of a CSF/serum index determination (on the basis of a comparison of IgG-antibody ELISA titers in CSF and serum with identical IgG concentrations) involvement of the nervous system was shown in 64% and 77%, respectively, of 76 stage II cases (diagnostic significance 98% and 100%, respectively). In particular when tertiary forms of the disease are suspected immunoblot techniques (Western blot, IEF-affinity blot) are recommended confirmatory tests. PMID- 1937324 TI - [Branhamella catarrhalis as a disease pathogen]. AB - Since 1980, numerous reports have been published throughout the world on the pathogenic role of Branhamella catarrhalis. Apparently, Branhamella infections have been increasing in many places. Although they can affect various organs, they are most commonly observed in the airways and eye (both in children and adults). Not infrequently, Branhamella catarrhalis causes sepsis, in particular in immunosuppressed patients. The rapid increase in beta-lactamase-forming Branhamella strains results in frequent ineffectiveness of treatment with penicillin. In patients treated with penicillin for a primary infection by other bacteria, a secondary infection due to penicillin-resistant Branhamella organisms can subsequently occur. For treatment, therefore, beta-lactamase-stable antibiotics should be preferred. PMID- 1937325 TI - [Uric acid level in blood donors of southern Germany--almost constant since 1971]. PMID- 1937326 TI - [Treatment of acute exacerbations of chronic bronchitis. Multicenter, randomized comparative study of cefuroxime axetil versus ofloxacin]. AB - 128 Patients (45 female, 83 male) with acute exacerbations of chronic bronchitis were treated with either cefuroxime axetil 2 x 500 mg/d (n = 65) or ofloxacin 2 x 200 mg/d for 7-8 days in a randomized controlled multicenter trial. From the respective groups, the results of 61 and 59 patients could be evaluated. Positive sputum tests were available in 85 cases (56 monoinfections, 29 mixed infections) prior to treatment. According to final clinical assessment, cure was achieved with cefuroxime axetil in 75%, but only in 50% with ofloxacin. The clinical efficacy of cefuroxime axetil was judged by the physicians to be more reliable than ofloxacin. The difference is statistically significant (p less than 0.05). Therapy with ofloxacin had to be terminated in 2 cases due to side effects. Altogether 4 adverse events were documented with ofloxacin. Compared with ofloxacin, cefuroxime axetil showed better efficacy and low risk of side effects. PMID- 1937327 TI - [Wakefulness during general anesthesia. Only a segment of combination anesthetics prevent perception of acoustic stimuli]. PMID- 1937328 TI - [Chlamydia infection. A common, usually mild, infection with often severe consequences]. AB - Today, chlamydiae are among the most frequently sexually transmitted organisms. At least 5 to 10% of young, sexually active adults, will have a florid chlamydial infection. On account of its chronic nature, the paucity of symptoms, and the difficulty in diagnosing it, this infection is still underdiagnosed. The spectrum of the manifested pathologies range from genital to abdominal lesions, to conjunctivitis, pneumonia and arthritis. On account of the specific intracellular reproduction cycle, antibiotic therapy is not always able to completely clear up the infection. Today, chlamydial infection is the most common cause of infection related sterility. During parturition, the neonate is often infected, with subsequent chronicity and sequelae. PMID- 1937329 TI - [Effect of omega-3-fatty acids on lipoprotein metabolism. Different effects in various phenotypes]. AB - A review of the literature confirms a regular and significant lowering of serum triglycerides by omega-3 fatty acids. This effect is the more pronounced the higher the initial levels are. Accordingly, in type V hyperlipoproteinemia, it is particularly marked. In normolipemic subjects and in patients with hypercholesterolemia (type IIA), total cholesterol is only slightly reduced. In patients with elevation of cholesterol and triglycerides (types IIB, IV and V), both triglycerides and cholesterol are lowered. This decrease is mainly obtained by reduction in VLDL cholesterol. In the case of types IV and V, on the other hand, triglyceride reduction is associated with an elevation of LDL and HDL cholesterol. At present, it is not clear whether the increase in LDL cholesterol is of a transient nature and prognostically irrelevant. It can be prevented by reducing the intake of saturated fat. HDL cholesterol is decreased by high doses and increased by low doses of omega-3 fatty acids. In the differential treatment of hyperlipoproteinemias, consideration should be given to these points. PMID- 1937330 TI - [Alcohol-induced ketoacidosis. Part 2: Therapy, follow-up and pathogenetic theories]. PMID- 1937331 TI - [Search for effective therapy of alcoholic liver damage. Comment on S. G. Schafer: "Propylthiouracil in therapy of alcohol-induced liver damage?"]. PMID- 1937332 TI - [Propylthiouracil in therapy of alcohol-induced liver damage?]. AB - Propylthiouracil (Propycil Thyreostat) is presently being used in hyperthyroidism, thyroidectomy, and other diseases affecting thyroid gland metabolism. Canadian clinicians have published interesting reports showing that propylthiouracil can be used to successfully treat alcohol-induced liver damage. In two clinical trials (approximately 340 patients) it was shown that long-term treatment with propylthiouracil was associated with a significantly more favorable prognosis in cirrhosis of the liver and with a reduction in mortality. Preclinical studies suggest that alcohol abuse leads to a hypermetabolic status of the liver, which is similar to hyperthyroidism. The results of these studies suggest a rationale for the use of propylthiouracil in alcohol-induced liver cirrhosis. PMID- 1937333 TI - [The heart in the elderly]. PMID- 1937334 TI - [Heart arrhythmias in advanced age]. AB - Holter monitoring has revealed that bradycardiac and tachycardic arrhythmias are frequent in apparently healthy subjects aged over 75. Even in elderly patients with known cardiovascular disease, however, such arrhythmias usually do not correlate with the clinical symptoms giddiness, palpitations or syncope. For this reason, prior to possible therapeutic measures, an accurate investigation of the underlying cause and the demonstration of a causal relationship between documented arrhythmias and symptomatology is necessary. Account must be taken of the particular pharmacotherapeutic situation in old age, in which the pharmacokinetics and pharmacodynamic properties of almost all drugs are modified. PMID- 1937335 TI - [Anti-arrhythmia drugs in geriatric patients]. AB - Owing to the special pharmacodynamic and pharmacokinetic situation in the aged, the therapeutic spectrum of antiarrhythmic agents is very narrow. The indication for these substances must be established in accordance with strict criteria. Once indicated, antiarrhythmic drug therapy must be initiated at the lowest possible dose, and increases in dosage must be gradual. Non-controlled empirical treatment with such drugs rejected, and the success or lack of success of such treatment must be checked using suitable methods, for example, Holter monitoring. Since the patients often have multiple diseases, particular attention must be paid to interactions with other drugs. Careful consideration must be given to the possibility of Cardiac side effects of antiarrhythmic agents such as proarrhythmic or negative inotropic effects. PMID- 1937337 TI - [Cardiac surgery interventions in patients over 70 years of age]. AB - In consequence of a longer life expectancy and improved surgical results, patients aged over 70 years now account for 10 to 15% of patients undergoing surgery on the heart. Such patients do, however, make greater demands on peri operative management; the adaptability of the cardiopulmonary and renal functions to stress is reduced, homeostasis is fragile, and the diseases that commonly accompany old age represent an additional risk. Furthermore, greater demands are also made on the operating skills of the surgeon. Nevertheless, no patient should be considered inoperable merely on account of advanced age. However, the indications for surgery must always be established on an individual basis, and against the background of the expected risk/benefit ratio. The biological rather than the chronological age is always decisive. The main aim of surgical treatment is to achieve an improvement in the patient's quality of life. PMID- 1937336 TI - [Positive inotropic substances. Possible use in heart failure in the aged]. AB - In the treatment of heart failure-also in the aged-digitalis preparations remain indispensable. At the present time, in particular in combination with diuretics and ACE inhibitors, they are experiencing a revival in the treatment of severe stages (NYHA stages III and IV). In addition, a spectrum of newly developed positive inotropic substances of various classes is now available. Among the catecholamines, apart from dopamine, dobutamine and their derivatives, new drugs with a beta-adrenergic agonistic effect are presently undergoing clinical testing. Another heterogeneous group of substances combine positive inotropic with vasodilatory properties. In this connection, mention might be made of the phosphodiesterase inhibitors, the H2 receptor antagonists, and certain catecholamine derivatives. However, digitalis remains the only substance that can be given orally over the long-term without tolerance developing. Particular aspects of the use of digitalis in geriatric patients are discussed. PMID- 1937338 TI - [Chemotherapy of colorectal cancer. Screening systems--value of special cytostatic drug combinations]. PMID- 1937339 TI - [30 years experience with haloperidol]. AB - Haloperidol, a butyrophenone derivative, was first used 30 years ago and has since become one the most frequently prescribed neuroleptics, employed in the treatment of numerous psychiatric and neurological syndromes. It has a very good antipsychotic effect; its sedative effects are moderate compared against weakly potent neuroleptics, and its vegetative side effects are only slight. In a review of the literature, the data found during the past 30 years are commented upon, such as data on pharmacodynamics, pharmacokinetics, indications, undesirable effects, interactions, dosage, contraindications and precautionary measures - all of them having implications on research on neuroleptics as a whole. PMID- 1937340 TI - [Cerebral ischemia in young adults]. AB - An overview is given over etiology and prognosis of cerebral ischemias until the age of 40. In a time period of 19 years, 168 patients were diagnosed with cerebral ischemia until the age of 40 (91 females, 77 males). The most frequent etiology is premature atherosclerosis in patients with vascular risk factors (up to 50%). Cardiogenic embolism is responsible for 1 to 34% of the cases: cardiac valve diseases and endocarditis being the most frequent sources. In 2 to 19% a vasculitis is diagnosed. While infectious arteritis is especially frequent in countries of the third world, immunovasculitides are common in Europe and the USA. Noninflammatory vasculopathies include spontaneous or traumatic dissection, fibromuscular dysplasia and vascular malformations. A migrainous stroke is especially frequent in female smokers with intake of oral contraceptives. During pregnancy both sinus thrombosis and arterial ischemia occur. Hematologic causes for ischemia are polycythemia, thrombocytosis and genetic diseases (sickle cell anemia, AT3-deficiency). Cerebral ischemia may occur in connection with the ingestion of ergot-derivates. The prognosis of cerebral ischemia in young adults is better than in older stroke-patients. PMID- 1937341 TI - [Progressive subcortical gliosis]. AB - A case of autoptically verified progressive subcortical gliosis (PSG) is reported. The 79 year old woman developed subacutely a right sided hemisyndrome and a cerebellar syndrome. Generalized action myoclonus of the left leg evolved into left sided Epilepsia partialis continua and dementia appeared. After a 6 month course the patient died of aspiration pneumonia. There was no indication of alcoholism or HIV-dementia neither clinically nor at autopsy. Morphologically the brain showed a diffuse proliferation of astrocytes in the subcortical white matter, thalamus, basal ganglia, brain stem and cerebellum. A severe neuronal dropout was found in medial thalamic neurons but Wernickes encephalopathy was ruled out. 21 cases of PSG confirmed by autopsy were found in the literature. Clinics, neuropathology and classification of PSG is discussed. PMID- 1937342 TI - [Clinical significance of intense signal foci in cerebral magnetic resonance tomography in neurofibromatosis--correction of a contribution by Mautner et al]. AB - The brief article is to correct errors of presentation and erroneous conclusions in the referred publication. It is shown that the neuropsychological resume drawn by the authors is invalidated by statistically significant findings already presented in the two diploma theses, upon which the previous authors drew. PMID- 1937343 TI - [Submicron particles in protein-peptide freeze-dry injections]. PMID- 1937344 TI - [Studies on pruritus in obstructive jaundice cases with special references to serum bile acid fractions]. AB - About, 22 cases with pruritus and 18 cases without pruritus of obstructive jaundice, serum bile acids were analysed quantitatively by high performance liquid chromatography (HPLC) before and after biliary decompression for the study on the relationship between pruritus and non-pruritus group. Analysis was also carried out on 11 cases with normal liver function as the control group. And 15 kinds of bile acids were as followed: unconjugates (ursodeoxycholic: UDCA, cholic: CA, chenodeoxycholic: CDCA, deoxycholic: DCA, lithocholic acid: LCA), glycine conjugates (Gly-UDCA, Gly-CA, Gly-CDCA, Gly-DCA, Gly-LCA) and taurine conjugates (Tau-UDCA, Tau-CA, Tau-CDCA, Tau-DCA, Tau-LCA). Data was analysed by t test statistically. [I] Before biliary decompression (1) No significant difference was observed between the pruritus group and non-pruritus group about total bile acid level, total unconjugates level and CA/CDCA ratio. (2) On total glycine-conjugates level the pruritus group was significantly lower than the non pruritus group, that level was about 3/5. Similarly on Gly-CA level was about 2/3, on Gly-CDCA level was about 1/2. (3) By contraries on total taurine conjugates level the pruritus group was significantly high as compared with the non-pruritus group, that level was about two times. Similarly on Tau-CA and Tau CDCA levels were about two times. (4) From there results on glycine/taurine ratio (G/T) of total bile acids pruritus group was significantly low as compared with the non-pruritus group, that level was about 1/3. Similarly on G/T ratio of CA level was about 2/5 and on G/T ratio of CDCA was about 1/3. (5) As for various unconjugates, UDCA level was significantly high in pruritus group as compared with non-pruritus group. [II] After biliary decompression No significant difference was shown in the composition of serum bile acids between the pruritus group and the non-pruritus group. These studies showed that the pruritus in the obstructive jaundice cases stood in a certain relation to the increase of taurine conjugates, especially taurine-conjugated CA and taurine-conjugated CDCA, moreover increase of unconjugated UDCA. PMID- 1937345 TI - [A case report of idiopathic myxedema with secondary amenorrhoea and hyperprolactinemia: effect of thyroid hormone replacement on reduction of pituitary enlargement and restoration of fertility]. AB - A 37-year old housewife was admitted to our department because of long-standing amenorrhoea and galactorrhoea. After several hormonal examinations, she was proved to be suffered from primary hypothyroidism with hyperprolactinemia. In addition, brain computed tomography (CT) showed the finding of enhanced pituitary enlargement, suggesting pituitary hypertrophy or pituitary adenoma. Based on some therapeutic experiences in similar cases in several reports, we have performed only thyroid hormone replacement and followed up the patient. Plasma thyroid stimulating hormone (TSH) and prolactin concentrations returned to normal range in a few months after starting thyroid hormone replacement. Furthermore, the finding of pituitary enlargement has completely disappeared on brain CT and come to pregnancy during the course. Thus, it seems that the finding of pituitary enlargement might be due to pituitary hypertrophy. Therefore, we think that thyroid hormone replacement should be a first choice therapy preceding the pituitary surgery or bromocriptine therapy in such a case. PMID- 1937346 TI - [A case of non-insulin-dependent diabetes mellitus associated with diabetic ketoacidosis after the onset of hyperlipidemia and acute pancreatitis following alcohol abuse]. AB - We report here a case of diabetic ketoacidosis associated with hyperlipidemia and acute pancreatitis following alcohol abuse. A 23-year-old man was admitted to the hospital because of right upper abdominal and back pain developing into a state of unconsciousness and shock. He had been drinking 720 ml of whisky daily for 4 years. Laboratory data on admission revealed metabolic acidosis (pH 7.01, PaO2 84.6 mmHg, PaCO2 41.1 mmHg, HCO3- 16.3 mmol/l, BE-16.4 mmol/l), a high blood glucose level (640 mg/dl), strongly positive urinary ketone bodies, hypercholesteremia (913 mg/dl) and hypertriglyceridemia (8500 mg/dl). Furthermore, the levels of pancreatic enzyme including serum amylase (770 U/l) and elastase I (2721 ng/dl) were elevated. After successful treatment of the diabetic ketoacidosis with insulin and fluid supplementation, serum cholesterol, triglyceride and pancreatic enzyme levels decreased concomitantly with stabilization of the blood glucose level. From these findings, it is suggested that hyperlipidemia might have caused the acute pancreatitis which developed into diabetic ketoacidosis in this patient. PMID- 1937347 TI - [A case of unstable diabetes mellitus after total pancreatectomy controlled by CSII]. AB - Continuous subcutaneous insulin injection (CSII) is one of good methods to control unstable diabetes. In this paper, we reported a case of a patient with unstable diabetes after total pancreatectomy, to whom CSII was very effective. The case was 53 years of age, lean woman. In 1980, she had pancreatoduodenectomy for the treatment of cancer of duodenal papilla. In June, 1986, she was diagnosed as recurrence of the cancer, and undertaken total pancreatectomy. And then, insulin treatment was commended. But she readily developed hypoglycemic reactions by ordinary insulin injection once or twice a day, and glycemic control was very poor. On April 22, 1987, CSII was started. 8 units of regular insulin were given during 24 hours, and 2 units of regular insulin were added before every meal. Thereafter, the frequency of hypoglycemic reaction decreased dramatically, and HbA1c level decreased from 8.5% to 8.1% three months later. This report indicated usefulness of CSII to patients with unstable diabetes, who couldn't be controlled by ordinary insulin injection. PMID- 1937348 TI - Lack of effect by nifedipine on hepatic mixed function oxidase in man. AB - Nifedipine (NF), a calcium channel blocker, is often prescribed in association with other drugs. Therefore, it was interesting to know whether or not, nifedipine, which is metabolized by the cytochrome P-450NF, was able to induce or to inhibit in vivo the activity of the hepatic mixed function oxidase system. The study was conducted in ten young healthy male volunteers receiving 20 mg NF slow release bid for 15 days. Due to the small number of subjects, comparison of the NF pharmacokinetics at dose 1 and 26 failed to show a bimodality in the frequency distribution of its area under the plasma concentration-time curve (AUC 274.5 to 317.1 ng ml-1 h, NS). Hepatic microsomal autoinduction (t1/2 2.87 to 3.06 h, NS) was not found. No statistically significant effect was seen on the aminopyrine breath test and on the debrisoquine metabolic molar ratio performed before and at the end of the treatment. Unlike what has been suggested by in vitro studies, NF treatment did not modify significantly the urinary excretion of 6 beta hydroxycortisol (318 to 265 micrograms/d, NS). After the last dose, the total oral clearance of NF was highly correlated with the metabolic clearance to 4 hydroxyantipyrine (r = 0.88; P = 0.005) but the other parameters of antipyrine biotransformation remained unchanged. We conclude that repeated nifedipine oral intake does not modify enzymatic activities of hepatic P-450 cytochromes involved in the biotransformation of antipyrine, aminopyrine, debrisoquine and cortisol. PMID- 1937349 TI - Pharmacokinetics of norfloxacin in the elderly. AB - 9 elderly and 9 younger adult patients, with proven post-operative lower urinary tract infection were treated with 400 mg of norfloxacin twice daily for 5 days. Pharmacokinetics of norfloxacin were measured on days 1 and 5. Compared to the younger adult patients, the elderly showed a decreased creatinine clearance and, following the last dose on day 5, an increased maximum plasma concentration of norfloxacin, an increased area under the concentration-time curve and a decreased total body clearance of norfloxacin. These results confirm that in elderly, as in younger adult patients, the pharmacokinetics of norfloxacin can be described by a linear model and accumulation of the drug during repetitive multiple doses is predictable. The differences between the two groups cannot be considered as clinically significant so that no dose change would be required in elderly patients within the range of creatinine clearance studied. PMID- 1937350 TI - Clinical consequences of polymorphic drug oxidation. AB - Many characters are genetically regulated as polymorphisms. This means that discrete groups are seen within the distribution of a certain character. Drug metabolism is no exception and the polymorphism of acetylation is recognised since the 50's. Polymorphic drug oxidation was discovered in the 70's and has been extensively studied. There are two fully established polymorphisms in drug oxidation named as the debrisoquine/sparteine and the s-mephenytoin hydroxylation polymorphisms. The metabolism of a number of important drugs cosegregates with that of debrisoquine. Among these drugs are beta-blockers, antiarrhythmics, tricyclic antidepressants and neuroleptics. Apart from accumulation of parent drug and active metabolite, also reduced formation of active metabolite occur for some drugs in slow metabolisers. There are, however, few cases where the presence of polymorphic drug metabolism is of significant disadvantage. The polymorphisms will add to variability in drug clearance but the potential clinical importance should be evaluated for each drug. The cytochrome P-450 isozyme responsible for debrisoquine hydroxylation is of high affinity-low capacity character, which means that it can be saturated under certain circumstances. This will decrease the difference in drug metabolic rate between rapid and low metabolisers as will inhibitors of the debrisoquine isozyme like cimetidine, quinidine and propafenone. The debrisoquine isozyme is not readily inducible. In cases where a major metabolic route or the formation of an active metabolite are polymorphically controlled, knowledge about a patient's oxidator status might be of practical value for dose adjustments especially if there is a narrow therapeutic ratio or an established concentration-effect relationship. For some drugs it is difficult to differentiate between insufficient therapeutic effect and symptoms of overdosage. Tricyclic antidepressants and neuroleptics meet some of these criteria and patients who get recurrent treatment may benefit if the physician has knowledge about debrisoquine metabolic phenotype. Otherwise, the clinical consequences of polymorphisms in drug oxidation seem so far to be limited, considering that a number of disease conditions have not shown any clear association with oxidation status. The polymorphisms in drug metabolism should be considered as a part of natural variability which could in fact be larger with other drugs that do not show polymorphic elimination. PMID- 1937351 TI - Behavioral effects of a calcium channel antagonist: nifedipine. AB - A series of experiments investigated the behavioral effects of a calcium channel antagonist, nifedipine. This antagonist has facilitatory effects on learning and memory as assessed by the active and passive avoidance tests respectively. In the forced swimming test, nifedipine at a dose of 5 mg/kg had an inhibitory effect on immobilization. Finally, nifedipine (2.5 and 5.0 mg/kg) induced an anxiolytic effect in the water consumption test in a novel environment. These findings are discussed with respect to other findings in the same field and to the neurochemical changes known to be induced by calcium channel antagonists. PMID- 1937352 TI - Effects of taurine on rat aorta in vitro. AB - The effects of taurine on vascular tone of isolated thoracic aortic rings were investigated. We have observed that: 1) taurine is able to induce reduction of the basal contractile tone; 2) taurine exerts a relaxing action in artery segments preconstricted with high potassium medium noradrenaline; 3) the effect of taurine is either dependent on endothelium, nor mediated by adrenoceptors or muscarinic cholinoceptors; 4) in vessels with basal tone or in those preconstricted with noradrenaline, the presence of endothelium reduces the taurine-induced relaxation; 5) the actions of taurine are independent of extracellular calcium; 6) taurine increases the vasodilatation induced by a perfusion with a calcium-free medium. The physiological role of taurine in the maintenance of vascular tone in normal and pathological situations is discussed. PMID- 1937353 TI - Upper gastrointestinal bleeding. PMID- 1937354 TI - Upper GI-bleeding--value and consequences of emergency endoscopy and endoscopic treatment. AB - Emergency endoscopy permits the early detection and prognostic evaluation of a source of hemorrhage. It serves as a "baseline" for decision-taking with regard to subsequent therapeutic measures. Today, modern endoscopic hemostatic procedures provide us with effective means of achieving primary control of the bleeding. Endoscopic emergency treatment can reduce the rebleed rate and help reduce the number of emergency surgical operations that need to be performed. A significant reduction in mortality rate has, so far, been observed in only a few comparative studies. When hemostasis has been accomplished, interdisciplinary discussions with the surgeon are needed in order to determine how to proceed in the individual case. PMID- 1937355 TI - Operative endoscopy in acute upper GI bleeding--indications, techniques, prognosis. PMID- 1937356 TI - Angiographic diagnosis and management. PMID- 1937357 TI - Upper gastrointestinal bleeding--indications and results in surgery. PMID- 1937358 TI - Endoscopic sclerotherapy--personal experience. AB - Over the last 12 years, treatment of bleeding esophageal and gastric varices has improved considerably. By the use of new techniques and with increased experience the results of endoscopic sclerotherapy have been optimized. Acute variceal bleeding, esophageal or gastric, can now be reliably and definitively stopped using the tissue adhesive Histoacryl Blau. This is also applicable to all patients irrespective of their liver status at presentation. As expected, the mortality of acute variceal bleeders has decreased considerably, no death from bleeding occurring in the last 5 years. This has obviated the need for emergency surgery, balloon tamponade or vasopressin infusion. Using an aggressive sclerotherapy technique in the bleeding-free interval, varices of all grades can now be effectively eliminated within an average of 3 sessions covering 3-4 weeks. With the intra- cum peri-variceal injection technique not only are the visible veins eradicated, but also fibrosis of the inner esophageal wall is achieved at the same time. If careful attention is paid to certain details of the technique and instruments, and with close follow-up, patients of portal hypertension can now live well in terms of liver function, without the danger of further variceal bleeding. PMID- 1937359 TI - Diagnostic emergency endoscopy in upper gastrointestinal bleeding--do we have any decision aids for patient selection? AB - The benefit of emergency endoscopy and therapeutic policies based on certain stigmata of bleeding has recently been demonstrated in patients with peptic ulcer hemorrhage. Applying a simple method of computer-aided diagnosis to a set of prospective data (n = 571) we investigated the question as to whether information on the history (28 variables) and clinical examination (8 variables) could be used to predict ulcer bleeding or certain stigmata of bleeding, with a view to deciding when to perform an emergency endoscopy in patients with upper gastrointestinal bleeding. The patients were assigned to either a high-risk group (probability greater than 0.50 for ulcer bleeding, arterial bleeding, etc.) or a low-risk group (p less than 0.50), and the prediction was compared with the actual findings at endoscopy. The results were disappointing, with an overall accuracy of 71% for the prediction of bleeding peptic ulcer and 71% for the prediction of a bleeding or non-bleeding visible vessel. Despite a relative risk of 2.8 for "bleeding ulcer" and 2.5 for "visible vessel" in the high-risk group, only 72% of all "bleeding ulcer" patients, and 69% of the "visible vessel" patients could be identified by the model. These results indicate that neither a bleeding ulcer nor stigmata of bleeding can be reliably predicted by the patient's history and clinical examination. Emergency endoscopy should therefore be performed in all patients with gastrointestinal bleeding. PMID- 1937360 TI - Changes in orientation of the major interlobar fissure in chronic liver diseases. AB - The orientation of the major interlobar fissure, as an indicator of right lobar atrophy, was evaluated using axial MR imaging in 64 patients with histologically proven chronic liver diseases. The "interlobar fissure angle" was determined by a line drawn through the middle hepatic vein and inferior vena cava and a horizontal line at the level of hepatic hilus. The angle was significantly smaller in cirrhosis than in either chronic persistent or active hepatitis. A much smaller angle was observed in cirrhosis associated with colonic interposition. The increasing incidence of small "interlobar fissure angle" (less than 30 degrees) was observed to parallel the histological stages from chronic persistent hepatitis to liver cirrhosis. All the cirrhotic patients with colonic interposition and an angle of less than 30 degrees. This simple method is considered useful in the diagnosis of right lobar atrophy and disease severity in chronic liver disease. PMID- 1937361 TI - Assessment of plasma fibronectin in Crohn's disease. AB - Plasma fibronectin concentrations were measured by an ELISA method in two groups of patients with Crohn's disease. In the first study the value of fibronectin as acute phase protein was determined in 48 patients. There was a poor but significant correlation (r = 0.294, p = 0.043) between disease activity and fibronectin concentration in these patients. However, fibronectin was found to show the best correlation with the disease activity of eight acute phase parameters tested. In the second study, the relation between development or presence of fibrosis/stenosis in the intestine of 91 patients with Crohn's disease was related to the plasma fibronectin concentration. The incidence of this type of lesion was found to increase with the level of fibronectin in the plasma together with the disease history of these patients, in particular when intestinal resection had to be performed. These observations reveal that assessment of fibronectin in plasma of patients with Crohn's disease is of limited value for the determination of disease activity, but that its concentration is related to the biological behavior, i.e. formation of fibrosis/stenosis, of the inflammatory lesion. PMID- 1937362 TI - Primary lymphoma of the common bile duct. AB - Primary lymphoma of the common bile duct is an extremely rare disease. Only two detailed case reports have been published in the literature. In the present paper, a 68-year-old female with obstructive jaundice and a primary lymphoma of the common bile duct, which was resected, is described in detail because of the rarity of the lesion in the literature. The cholangiogram demonstrated stricture of the common bile duct. The findings at angiography and computed tomography were non-specific, but a hypo-echoic mass filling the lumen of the bile duct was demonstrated by ultrasonography. Subtotal resection of the common bile duct and cholecystectomy was performed as the method of choice, although the frozen section examination was not definitive. The final histological diagnosis was malignant lymphoma of the diffuse, small cleaved cell type. There was no metastasis to dissected regional lymph nodes. External irradiation was effective when recurrent tumors were found six months later. However, the patient developed generalized disease one year after resection. Although combination chemotherapy was effective this time for her lymphadenopathy, she died of pneumonia one year and four months after surgery. It can be postulated that ultrasound would be useful in diagnosing this rare entity, and that adjunctive radiotherapy after resection would be preferable to prevent progression of the disease. PMID- 1937363 TI - Immunohistochemical detection of ras p21 and c-myc p62 in colonic adenomas and carcinomas. AB - In the present paper we review the results of our study on the use of monoclonal antibodies Y13,259 to the ras p21 and MYC1 9E10 to the c-myc p62 oncoprotein products in human tumors and tumorlike conditions of the colorectum. A total of 78 tissue sections were analyzed immunohistochemically and revealed the following: 42 adenocarcinomas with 8 normal mucosae adjacent to the tumor, 25 adenomas (with or without dysplasia and with in situ carcinoma) and 3 hyperplastic polyps. Parallel tissue sections were used in order to compare ras and c-myc oncoproteins. Reviewing our results we made the following remarks: 1. All adenocarcinomas but one were expressed with both oncoproteins, most of them being strongly positive. 2. All adenomas were positive for ras p21, and all but two were also positive for c-myc p62. An interesting point is that the degree of staining intensity increased in accordance with the degree of dysplasia and/or in situ carcinoma association. 3. The hyperplastic polyps, as well as all normal mucosae were negative. PMID- 1937364 TI - Factors affecting the diameters of the common bile duct and pancreatic duct using endoscopic retrograde cholangiopancreatography. AB - Endoscopic retrograde cholangiopancreatography (ERCP) findings in 405 patients were analyzed to compare common bile duct (CBD) and main pancreatic duct (PD) diameters in relation to age, sex, gallbladder stones, CBD stones and acute pancreatitis. There were 129 patients with gallstones uncomplicated by pancreatitis, 131 patients with pancreatitis, and 145 control subjects. Significant correlations were found between CBD and PD diameters, and between these and age. Independently significant determinants of the CBD diameter were age, female, sex, CBD stones and gallbladder stones, as well as PD diameter. Conversely, PD diameter was significantly dependent upon age, CBD diameter, and acute pancreatitis. This study suggests that both CBD and PD dilation occurs in patients with gallstone disease. In view of the different factors which affect CBD and PD diameters (particularly age), important clinical decisions previously recommended on the basis of these duct diameters may need to be qualified. PMID- 1937365 TI - Modern technology in surgical practice--surgical anatomy of the normal liver as revealed by preoperative ultrasonography. PMID- 1937366 TI - Reversal of primary liver graft non-function using prostaglandins. AB - Primary graft non-function remains one of the most life-threatening problems after liver transplantation. Its etiology is still unclear. Liver retransplantation is the only therapeutic alternative to this problem. The PGE1 series of prostaglandins have recently been successfully used in the treatment of transplanted organ dysfunction. In this paper we describe a case of primary graft non-function successfully treated with continuous infusion of prostaglandin PGE1, and we briefly discuss the pathogenetic and therapeutic hypotheses. PMID- 1937367 TI - Risk factors in abdominal surgery. AB - The term risk is understood to be the danger of the occurrence of an undesired, life-threatening event. The probability of this undesired event is greater in the presence of a risk factor than in its absence. In general surgery, these risk factors can be classified into five groups: The environment, the surgeon, the operation per se, the disease, and the patient himself. Abdominal surgery is especially suited to clarify and to illustrate this classification. Some typical risk factors are described, and for each group the measures for risk prevention or risk reduction are discussed. PMID- 1937368 TI - Infectious complications and risks in abdominal surgery; early recognition and prevention. PMID- 1937369 TI - The thrombo-embolic risk in surgery. AB - Postoperative deep-vein thrombosis can lead to fatal pulmonary embolism on one side, and the development of a disabling postthrombotic syndrome, which can occur after some time. General thrombo-embolic prophylaxis can reduce the risk of postoperative thrombo-embolic complications. Predisposing factors include age, obesity, immobilization and recumbency. Cardiovascular diseases, malignant neoplasms, venous disorders, diseases associated with increased viscosity of blood, past deep-vein thrombosis and pulmonary embolisms, some infectious diseases with raised fibrinogen levels, and inherited or acquired clotting factor deficiency syndromes (antithrombin III, protein C, protein S) have an elevated risk of thrombosis. The surgery itself, when taking more than 20 minutes and performed under general anesthesia, is a major risk factor, as proven initiation of thrombosis is often on the operation table. Patients receiving regional or local anesthesia have a clearly reduced risk of thrombosis. After general surgery without thrombosis prophylaxis, a deep-vein thrombosis can be demonstrated by the fibrinogen uptake test in about 30% of all patients over the age of 40. After abdominal surgery an incidence of thrombosis of 14-33%, and after hip surgery an incidence of nearly 50%, have been established by means of the fibrinogen uptake test. However only 10% of these thromboses are expressed clinically. We therefore recommend Liquid Crystal Contact Thermography, which has a sensitivity of 94% and a specificity of over 80%, as a non-invasive, easily performed screening method in the diagnosis of deep-vein thrombosis. Apart from the physical methods, the use of heparin is also indicated in thrombo-embolic prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937370 TI - Emergency room patients with abdominal pain unrelated to trauma: prospective analysis in a surgical university hospital. AB - During an 8-month-period, 241 patients suffering from abdominal pain unrelated to trauma (mean age 48 years) attended the emergency room of the Department of Surgery of the University Hospital, Zurich. Forty-three percent presented during working hours, while 57% were admitted during the night or at the weekend. Clinical examination, abdominal roentgenograms (upright and supine) and sonography were the most commonly used diagnostic tools. Forty percent suffered from abdominal pain of unknown origin. The most common diagnosis on admission was appendicitis, but only half of these cases proved to be appendicitis. In 36% the diagnosis on admission corresponded both to the initial diagnosis made by a member of staff during his first visit, and to the final diagnosis. The initial diagnosis agreed with the final diagnosis in 57%. In 10% of the patients the cause of pain was not elucidated despite extensive diagnostic procedures. High technology and sophisticated diagnostic evaluation are less important than the clinical evaluation. The decision between operative and nonoperative treatment was based mainly on clinical findings. PMID- 1937371 TI - Peritoneal adhesions after laparotomy: prophylactic measures. AB - Abdominal adhesions are due to a locally decreased peritoneal fibrinolytic capacity occurring mainly in ischemic areas of the peritoneum. They help to guarantee the supply of blood to these areas, acting as a protective mechanism ("vascular graft"). With respect to abdominal surgery a general suppression of the ability to form adhesions would therefore seem to be questionable. We consider the currently employed or discussed methods with their advantages and disadvantages. No optimal solution to the problem of adhesions has been found so far. Nevertheless, appropriate surgical technique can permit us to control adhesion formation to a certain degree. If adhesions are unavoidable, placement of the greater omentum should be done carefully in the areas of risk. PMID- 1937372 TI - The effect of omeprazole and ranitidine on ulcer healing, relief of symptoms, and incidence of adverse events in the treatment of duodenal ulcer patients. AB - In a Swedish double-blind multicenter study involving 143 patients, the new proton pump inhibitor omeprazole (30 mg taken as a single morning dose) was compared with ranitidine (400 mg b.i.d.). Clinical assessment and laboratory investigations were carried out at 2 and 4 weeks, and again at 6 weeks if patients had not healed earlier. Endoscopy was repeated at two-weekly intervals until the ulcer was healed. The patients in the two treatment groups were well matched prior to treatment. There was a higher ulcer healing rate in the omeprazole group (70%) than in the ranitidine group (55%) after two weeks of treatment. This difference reached statistical significance in 128 patients adhering to the protocol as shown by a logit model analysis with drug, ulcer size and smoking as the prognostic factors (p = 0.04). There were no major differences between the two treatment groups in terms of symptomatic relief. Both drugs were generally well tolerated, and the number of adverse events in the two treatment groups were similar. After healing, 127 patients entered a follow-up study, with endoscopy either after 6 months or on recurrence of symptoms. There was no significant difference between the two treatment groups, with the relapse frequency within 6 months being 39% in the omeprazole group and 47% in the ranitidine group. These results, with a 15 percentage points higher ulcer healing rate for omeprazole as compared with H2-receptor antagonists after two weeks, are in accordance with results reported in other studies. PMID- 1937373 TI - Endoscopic injection to arrest peptic ulcer hemorrhage: a prospective, randomized controlled trial; preliminary results. AB - Over a period of 10 months, we conducted a prospective randomized controlled trial of endoscopic injection for the arrest of peptic ulcer hemorrhage in 84 patients. We injected pure alcohol (PA, 99.8%), 50% glucose in water (G/W), 3% NaCl solution, and normal saline solution (N/S, controls) to stop bleeding. The ultimate success rates in the four groups were: 81% (17/21) in the PA group, 80% (16/20) in the 50% G/W group, 65.2% (15/23) in the 3% NaCl group, and 80% (16/20) in the N/S group (p greater than 0.05). The volume of blood transfusion (mean +/- s. e. m.) for each patient was 1,200 ml +/- 433 ml in the PA group, 1,130 +/- 356 ml in the 50% G/W group, 1,704 +/- 330 ml in the 3% NaCl group, 1,400 +/- 548 ml in the N/S group (p greater than 0.05). The duration of hospitalization (mean +/- s. e. m.) was 5.7 +/- 1.5 days in the PA group, 3 +/- 1.3 days in the 50% G/W group, 6.1 +/- 1.1 days in the 3% NaCl group, and 5 +/- 1.1 days in the N/S group (p greater than 0.05). No complication of perforation or aspiration pneumonia was observed during hospitalization. We suggest that endoscopic injection with the above solutions be used as the first line of therapeutic endoscopy for arrest of peptic ulcer hemorrhage. PMID- 1937374 TI - Ten versus 28 days of cimetidine treatment for duodenal ulcer in Iran. Evidence for the need for risk-oriented individual treatment of ulcer patients. AB - A clinical trial involving 100 duodenal ulcer patients was performed at the Shiraz Medical School in Iran, in which the known risk factors that influence the healing of duodenal ulcers in West Germany were examined. The patients were randomly allocated to groups receiving 2 x 400 mg cimetidine daily for 10 days (group I) or 28 days (group II). In addition, antacid was taken if pain occurred. Probable prognostic risk factors were noted, such as: age, sex, duration of ulcer history, duration of the present ulcer relapse, smoking habit, nocturnal pain, radiation of pain to the back, history of ulcer bleeding and use of analgesics. The number of ulcers, ulcer size, ulcer depth, bulbar deformity and narrowing were determined endoscopically. Follow-up examinations were performed in 89 patients 4 weeks after the start of treatment. The ulcers were healed in 20 out of 43 patients in group I (46%), and in 29 out of 46 in group II (63%) (p = 0.11). Statistical analyses were performed in both group combined to investigate unfavorable factors for healing. Following univariate analysis the following factors were prognostically unfavorable: bulb deformity (p = 0.003), radiation of pain to the back before treatment (p = 0.045), number of cigarettes smoked per day (p = 0.046). The patients with non-healed ulcers had more days with pain during treatment (p = 0.045). Using logistic regression analysis, the following prognostic factors were significant: number of cigarettes smoked per day (p = 0.03), radiation of pain to the back (p = 0.036), and bulb deformity (p = 0.048).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937375 TI - 24-hour study of gastric acidity in normal subjects and in cholecystectomized patients using continuous pH monitoring. AB - The circadian pattern of gastric acidity was assessed in 53 normal subjects and in 33 patients with prior cholecystectomy using continuous pH monitoring. The 24 hour and nocturnal median pH values were significantly higher in cholecystectomized patients than in controls (p less than 0.03 and p less than 0.001, respectively). In the operated group there were higher median pHs also in the after-dinner (p less than 0.003) and after-lunch (p less than 0.01) periods, while no difference between the two populations was observed after breakfast. The percentage of 24-hour pH readings above 4.0 units was markedly higher (p approximately 0) in postcholecystectomy patients. We conclude that circadian gastric acidity is reduced in cholecystectomized patients with respect to healthy subjects, both in nocturnal and postprandial states. Episodes of duodenogastric reflux may be responsible for this, but impaired acid production related to advanced age (14 patients were more than 60 years old) or to fundic chronic atrophic gastritis (5 cases) may also account for the elevation of pH values in our postcholecystectomy patients. PMID- 1937376 TI - Interleukin-2 and natural killer activity in acute type B hepatitis. AB - Natural killer (NK) cell activity against K562 cell line, and interleukin-2 (IL 2) activity in supernatants from lectin-activated PBMC cultures from 17 patients with acute hepatitis B in the early phase of illness were studied. These patients showed enhanced NK cytotoxicity and higher levels of IL2 activity as compared with control subjects. There was a positive correlation between cytotoxicity values and levels of IL2 activity. Furthermore, in the recovery phase of illness there was a tendency towards normalization in both parameters. When patients were divided in accordance with markers of HBV replication, HBV-DNA positive patients showed increased NK cell activity and IL2 levels as compared with the control group, whereas in HBV-DNA-negative patients no differences were found. However, no differences were found between patients with HBeAg and patients with anti-HBe. These results suggest that natural cytotoxicity is increased early in the course of acute hepatitis B, while NK cell activity returns to normal later, during convalescence. Enhanced NK cell activity appears to be secondary, at least in part, to increased production of IL2. Natural cytotoxicity may be one mechanism that controls the HBV infection before other cytotoxic mechanisms become fully operative. PMID- 1937377 TI - Bowenoid change in perianal condyloma acuminatum associated with ulcerative colitis. AB - A 35-year-old male patient with a 20-year history of ulcerative colitis developed an itching perianal condyloma acuminatum with discharge. This was surgically removed after two years. Histology revealed bowenoid change in the condyloma. Six months later a local recurrence was excised. He has now been free of further recurrence for 5 years. Electron microscopy showed moderately differentiated keratinocytes in the areas of bowenoid change. There was no evidence of virus particles in the keratinocytes. A causal relationship has been assumed between the ulcerative colitis, via chronic irritation, and the perianal bowenoid changes regarded as in situ carcinoma. The importance of radical excision of such lesions is emphasized. PMID- 1937378 TI - Perhexiline maleate-induced hepatitis. AB - We report on a case of perhexiline maleate-induced hepatitis secondary to a long term administration of recommended daily dosages of 300 mg. The patient had a spectacular weight loss of 29 kg. He developed hepatitis, which subsided after drug withdrawal. Our electron-microscopic findings with the typical inclusion bodies and impaired hydroxylation capacity point to an underlying metabolic disorder as the pathogenetic mechanism. PMID- 1937379 TI - Pyogenic liver abscess: a 7-year experience in a large community hospital. AB - This is a retrospective study of 27 consecutive patients with a diagnosis of pyogenic liver abscess (PLA) seen over a period of 7 years. There were 10 males and 17 females whose ages ranged from 5 to 86 years (mean 56). Fever, abdominal pain and vomiting were the commonest symptoms, and abdominal tenderness was the commonest physical finding. An elevated alkaline phosphatase was seen in 78% of all patients and was the commonest biochemical abnormality. Biliary disease accounted for a third of all cases, and in 22% of the patients the abscesses were considered to be idiopathic. Ultrasonography and/or CT scanning was employed in the diagnosis and follow-up of all patients. Percutaneous needle aspiration (PNA) and percutaneous drainage (PCD) under ultrasound or CT guidance was employed as the primary therapy in 24 patients. The procedure failed in 5 patients (18.5%), there was 1 complication (3.7%) and no deaths were seen as a result of these procedures. Three patients (11%) ultimately died of their abscesses. This study emphasizes the important role of percutaneous drainage as a complementary form of therapy to surgical drainage in the management of pyogenic liver abscesses. PMID- 1937380 TI - Clinical profile in Barrett's esophagus: who should be screened for cancer? AB - A retrospective survey identified 96 patients (58 males) with Barrett's esophagus, diagnosed at the Royal Melbourne Hospital between 1978 and 1986. The age at presentation varied from 20 to 93 years, and 43% were greater than 70 years. Heartburn was a presenting symptom in 71%, regurgitation into the pharynx in 54%, dysphagia in 31% and hematemesis or melena in 29%. At endoscopy, the length of Barrett's epithelium ranged from 3 cm to 15 cm. Macroscopic esophagitis was observed in 69%, benign esophageal strictures in 14% and a co-existent adenocarcinoma of the lower esophagus in 10% of patients. Only 30% of the patients were cigarette smokers at the time of diagnosis, but 64% drank alcohol (9% greater than 80 g alcohol daily). Patients with esophageal cancer at presentation were more likely to be male and cigarette smokers (Fisher's exact probability test). It has been suggested that patients with Barrett's esophagus should be screened to detect the early development of esophageal cancer. If patients who already have cancer, the elderly (age greater than 70 years) and those with a chronic alcohol problem (greater than 80 g intake daily) are excluded from endoscopic cancer surveillance, only 42% of the patients described in this survey would be eligible for enrollment in such a program. This represents a recruitment of only 5 new patients yearly in a large teaching hospital endoscopy unit. PMID- 1937381 TI - Intraobserver and interobserver variation in the histopathological assessment of liver allograft rejection. The Liver Transplantation Database (LTD) Investigators. AB - A study to determine the reproducibility of histopathological findings and diagnoses of rejection was carried out on a series of 42 liver allograft needle biopsy specimens by five pathologists practicing at four liver transplant centers. Pathologists from each of the four centers read each slide independently on two different occasions and were asked to assess 12 histopathological features and render a diagnosis. For all histological variables, the intrarater agreement was higher than the interrater agreement. Moderate to excellent agreement occurred among the pathologists about all histological variables thought to be important in establishing the diagnosis of acute rejection (i.e., portal tract inflammation, subendothelial inflammation and bile duct damage). Other variables such as lobular disarray, bile duct proliferation and particularly arteritis, however, were only fairly or poorly reproducible. Surprisingly, the diagnosis of acute rejection was more reproducible than the individual histopathological findings that were thought to be the basis for the diagnosis. The agreement for the diagnosis of chronic rejection, however, varied according to observer. We noted that relatively inexperienced observers within this group had some difficulties agreeing with more experienced observers in establishing a diagnosis of chronic rejection. These findings demonstrate that the histopathological diagnosis of acute cellular liver allograft rejection is highly reproducible within a group of experienced pathologists and that this diagnosis can be pooled in a common data base with confidence. PMID- 1937382 TI - Gallstones in cystic fibrosis: a critical reappraisal. AB - Radiolucent gallstones are common in young adults with cystic fibrosis. In the mid-1970s, it was suggested that gallstones are made of cholesterol, but this hypothesis has never been tested. Several recent studies have shown that the detection of cholesterol monohydrate crystals in bile has high sensitivity and specificity for the diagnosis of cholesterol gallstones. We therefore used this approach to study 17 young adults with cystic fibrosis, 10 of whom had radiolucent gallstones. The two groups of patients were comparable in age and gender (all patients but one were male). Duodenal bile was obtained after gallbladder contraction with intravenous cerulein; it was used for lipid and protein chemistry studies and for polarizing microscopy. The latter was performed both in whole bile and in the postultracentrifugation (100,000 g) sediment. Bile cholesterol saturation did not significantly differ between patients with (1.21 +/- 0.28) or without gallstones (0.99 +/- 0.54). Slight cholesterol supersaturation was found in 7 of 10 gallstone and three of seven nongallstone patients. At no time were cholesterol crystals detected in either the group, even after bile ultracentrifugation. Two more cystic fibrosis patients with gallstones died of severe bronchopneumopathy, and small pigment gallstones were obtained at autopsy. At stone analysis, cholesterol content was 44% and 28% of dry weight, respectively. Infrared spectroscopy of stone powder was compatible with the presence of calcium bilirubinate and proteins as major components. We conclude that radiolucent gallstones of cystic fibrosis are not of the conventional cholesterol type. PMID- 1937383 TI - In situ immunophenotyping study of endothelial cells of the human hepatic sinusoid: results and functional implications. AB - Hepatic sinusoids are highly specialized capillary vessels characterized by the presence of resident macrophages adhering to the endothelial lining. Although it is likely that sinusoidal endothelial cells have specific adaptations, little is known about the roles that they actually play in vivo. We therefore designed an in situ immunophenotyping study of sinusoidal endothelial cells in normal human liver to compare this population with those of the other vascular compartments of the liver and to determine whether it expresses molecules involved in the following physiological processes: scavenging and nonspecific immune functions, antigen presentation and endothelial-leukocyte adhesion. Our study showed that sinusoidal endothelial cells displayed a highly distinctive immunophenotype characterized by the expression of several molecules not found in the other vascular compartments of the liver. A first group of molecules restricted to sinusoidal endothelial cells were: the receptors II and III for the Fc fragment of IgG; the CD14 molecule, serving as a receptor for the lipopolysaccharide binding protein; and aminopeptidase N. The presence of those molecules suggests that sinusoidal endothelial cells contribute to the scavenger and nonspecific immune functions of hepatic sinusoids. No direct evidence for an antigen presenting function of this cell population was obtained. Another group of proteins restricted to sinusoidal endothelial cells comprised the leukocyte adhesion molecules CD4 and intercellular adhesion molecule-1, which may be involved in the adhesion of Kupffer cells to the sinusoidal wall. Therefore our immunophenotyping study makes it possible to provide an in situ demonstration of the phenotypical and functional diversity of endothelial cells in normal human liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937384 TI - Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage. AB - Little is known about factors determining individual susceptibility to the physical complications of alcohol abuse but genetically determined differences in ethanol metabolism may be important. The oxidative metabolism of alcohol is catalyzed by alcohol and aldehyde dehydrogenase. Polymorphisms have been observed at two of the five loci encoding alcohol dehydrogenase subunits: ADH2 (producing three beta subunits) and ADH3 (producing two tau subunits) and also at the locus encoding the metabolically important form of aldehyde dehydrogenase, ALDH2. We have compared ADH2, ADH3 and ALDH2 allele frequencies in patients with alcohol related cirrhosis (n = 59) and chronic pancreatitis (n = 13) with 79 local healthy control subjects. The different alleles were detected with allele specific oligonucleotide probes after amplification of leukocyte DNA by the polymerase chain reaction. All patients and all but one control subject were homozygous ADH2*1, encoding the beta 1 subunit. No ADH2*3 alleles were detected. All 34 patients and 39 control subjects tested were homozygous ALDH2*1 encoding the active enzyme. ADH3 allele frequencies were different in patients and control subjects. ADH3*1 frequency: control subjects, 55.1%; cirrhotic patients, 62.7%; chronic pancreatitis patients, 65.4%. The difference between the patient groups combined and the control subjects was significant (p less than 0.05; G-test of Sokal and Rohlf) if it was assumed that the allele frequency in our control population was a reasonable estimate of our local population allele frequency. These results suggest that genetically determined differences in alcohol metabolism may, in part, explain predisposition to alcohol-related end-organ damage. PMID- 1937385 TI - Azathioprine hepatotoxicity after liver transplantation. AB - We report the first two cases of apparent azathioprine hepatotoxicity occurring after liver transplantation. The two patients exhibited jaundice, elevated serum transaminase activities and histopathological features of sinusoidal congestion and centrilobular hepatocellular degeneration 17 and 61 days after transplantation. After withdrawal of azathioprine, liver test results improved immediately in both patients. Recurrence of liver injury after another challenge with azathioprine was seen in the first case. Previously, fatal venoocclusive disease occurring after kidney transplantation had been attributed to azathioprine. Irreversible venoocclusive disease and the reversible hepatotoxicity described in this report (i.e., sinusoidal congestion with centrizonal necrosis) most likely represent different stages of hepatic endotheliitis caused by azathioprine. Thus early diagnosis of azathioprine hepatotoxicity is of great importance. PMID- 1937386 TI - Hepatocellular peroxisomes in human alcoholic and drug-induced hepatitis: a quantitative study. AB - The peroxisomes in the liver of four patients with alcoholic hepatitis and in six patients with drug-induced hepatitis are compared to eight control livers by catalase cytochemistry and morphometry. A decrease of catalase activity is observed in alcoholic, amitriptyline, aprindine, clomipramine and methiomazole hepatitis. Peroxisomes with a heterogeneous distribution of the catalase reaction product are found in most hepatitis livers. The number of organelles is increased 1.5 to 4.2 times in alcoholic, aprindine, methimazole and phenytoin hepatitis livers. In the last case, peroxisomes are also smaller. Changes in shape are seen in all hepatitis livers; they include invaginations, tails, funnel-like constrictions and gastruloid cisternae. In aprindine, phenytoin, methimazole and two alcoholic hepatitis livers, surface density exceeds the upper control value. These data indicate a loss of catalase activity in most hepatitis livers but also peroxisomal proliferation and shape modifications. It has been proposed that the latter changes are favorable for metabolic activity. PMID- 1937387 TI - Reduction of morbidity and mortality from biliary complications after liver transplantation. AB - Over a 4-yr period that began October 1, 1986, 103 orthotopic liver transplants were performed on 91 patients at the Johns Hopkins Hospital. Biliary reconstruction at the time of transplantation was performed in standard fashion by an appropriately trained member of the surgical team. Six (7%) patients developed biliary complications, which included three cases of common bile duct stricture and one case each of bile duct obstruction caused by biopsy-related hemobilia, biloma and a retained fragment of a T tube after removal. Five of the six patients were treated successfully by nonoperative interventional radiological procedures performed under local anesthesia with light intravenous sedation. Reoperative surgery (to remove the T-tube fragment from subcutaneous tissue) was required for only one patient, and no deaths (0 of 91) were attributable to biliary complications. All six patients are alive and well 6 to 33 mo after the operation with excellent liver function. Our findings would suggest that most biliary complications of orthotopic liver transplants are avoidable and that the few that do appear can usually be managed both safely and effectively by an interventional radiological approach. PMID- 1937388 TI - Effect of propranolol on portosystemic collateral circulation in patients with cirrhosis. AB - Propranolol has been demonstrated to be effective in lowering portal pressure in cirrhotic patients. This effect is mediated by a reduction of splanchnic arterial inflow and a consequent decrease of portal vein and portocollateral blood flow. Although experimental studies suggest a direct effect of the drug on portocollateral circulation, little information exists about relative flow changes occurring in the portal vein and in collateral veins feeding esophageal varices. This study addressed the problem in 12 cirrhotic patients selected on the basis of feasibility of Doppler flowmetry in both the portal and left gastric veins. Caliber, flow velocity and flow volume in both vessels were measured by Doppler ultrasound before and at 60, 120 and 180 min after an oral dose of 40 mg propranolol, together with heart rate and mean arterial pressure. A significant decrease in heart rate (-17.6% +/- 1.1%, p less than 0.001) and mean arterial pressure (-10.6% +/- 0.9%, p less than 0.005) confirmed effective beta-blockade. Baseline flow velocity was significantly lower in the portal vein than in the left gastric vein (12.4 +/- 0.6 vs. 15.4 +/- 1.5 cm/sec, p less than 0.05). Maximal hemodynamic effect was reached at 120 min after administration of propranolol. The vessel caliber did not change significantly. Flow velocity fell from 12.4 +/- 0.6 to 10.4 +/- 0.7 cm/sec in the portal vein (p less than 0.05) and from 15.4 +/- 1.5 to 11.1 +/- 0.9 cm/sec in the left gastric vein (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937389 TI - Regulation of bile acid synthesis in humans: effect of treatment with bile acids, cholestyramine or simvastatin on cholesterol 7 alpha-hydroxylation rates in vivo. AB - The rates of cholesterol 7 alpha-hydroxylation (the first and rate-limiting step of bile acid synthesis from cholesterol) were evaluated in vivo in patients administered bile acids with different structural properties, cholestyramine or simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Twenty-three subjects, with normal hepatic and intestinal functions, were studied in basal conditions and after one of the following treatment schedules, lasting 4 to 6 weeks: cholestyramine, 4 and 12 gm/day (four patients); ursodeoxycholic acid, 9 to 11 mg/kg/day (four patients); chenodeoxycholic acid, 12 to 15 mg/kg/day (five patients); deoxycholic acid, 8 to 10 mg/kg/day (four patients); and simvastatin, 40 mg/day (six patients). 7 alpha-Hydroxylation of cholesterol was assayed by measuring the increase in body water tritium after intravenous bolus of cholesterol tritiated at the 7 alpha position. Plasma bile acid composition, evaluated by gas-liquid chromatography, revealed a substantial enrichment of the recirculating pool by the administered bile acid, whereas treatment with cholestyramine decreased the content of dihydroxylated bile acids. Cholesterol 7 alpha-hydroxylation increased in a dose-related manner after cholestyramine, in parallel with a decrease of cholesterol in total plasma and low-density lipoproteins (1.006 to 1.063 gm/ml). Hydroxylation rates decreased by an average of 47% with chenodeoxycholic acid and by an average of 78% with deoxycholic acid; ursodeoxycholic acid treatment did not affect 7 alpha hydroxylation significantly. Simvastatin markedly reduced plasma total and low density lipoprotein-cholesterol but exerted no change on 7 alpha-hydroxylation rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937390 TI - Ursodeoxycholic acid for the treatment of primary sclerosing cholangitis: a 30 month pilot study. AB - We investigated the effects of once-daily oral administration of 10 mg/kg ursodeoxycholic acid (generic name, ursodiol) on elevated serum enzyme activities, bilirubin, cholesterol, bile acids and symptoms in patients with primary sclerosing cholangitis. A 30-mo, open-label, pilot trial was designed to cover four periods: (a) 3 mo of pretreatment observation (period 1), (b) 6 mo on ursodiol (period 2), (c) 3 mo withdrawal of treatment (period 3) and (d) 18 mo of extended retreatment (period 4). Diagnosis was confirmed by cholangiography and liver biopsy specimens. We enrolled 12 patients with persistently elevated pretreatment alkaline phosphatase and gamma-glutamyltransferase levels (at least twice the upper limit of normal), and observed them for a median of 37 mo. Significant reductions in serum total cholesterol levels and in serum enzyme activities indicating cholestasis and hepatocellular injury occurred during ursodiol treatment in both treatment periods 2 and 4 and relapsed with treatment interruption in period 3. Elevated serum bilirubin and symptoms of disabling fatigue, pruritus and diarrhea were improved by ursodiol. Improvements have continued after 2 yr of treatment in 10 patients (1 patient had a transplantation after he relapsed on withdrawal of ursodiol therapy; another died of postoperative complications of colon resection for carcinoma). No other cases of clinical deterioration were observed in the retreatment period. The longer term reductions of alkaline phosphatase, transaminases, bilirubin and cholesterol after 2 yr of treatment were even greater than the initial reductions after 6 mo of treatment. These results justify initiation of larger, controlled clinical trials, with serial morphological evaluations of the liver and biliary tree. PMID- 1937391 TI - Isolation and characterization of a novel liver-derived immunoinhibitory factor. AB - Cytosolic extracts prepared from perfused whole liver or purified hepatocytes of C57BL/6 mice inhibited interleukin-2--and concanavalin A--induced spleen cell proliferation in vitro. In contrast, cytosolic extracts from purified nonparenchymal liver cells had no effect. Arginase and very-low-density lipoprotein were previously identified as two immuninhibitory substances present in liver cytosolic extracts. We demonstrated, however, that inhibitory activity remained after removal of very-low-density lipoprotein and arginase from liver cytosolic extract by repeated ultracentrifugation and gel filtration chromatography, respectively, suggesting the presence of another inhibitor. Further purification by anion-exchange chromatography and chromatofocusing led to the isolation of a novel liver-derived immunohibitory factor. This liver-derived immunoinhibitory factor is sensitive to pronase digestion and heat and acid treatment; it has an estimated isoelectric point of 8.25. The Mr of liver-derived immunoinhibitory factor is 28 kD as estimated from its migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which is identical under both reducing and nonreducing conditions, indicating a monomeric nature of this protein. Amino acid composition analysis discloses that liver-derived immunoinhibitory factor is relatively rich in glycine and proline residues. Interleukin-2--induced spleen cell proliferation in vitro is inhibited by ths liver-derived immunoinhibitory factor, with a 50% inhibitory dose of 1.4 nmol/L. Furthermore, the biological activity of the liver-derived immunoinhibitory factor is not confined to mouse spleen cells, since the growth of B16 mouse melanoma and H35 rat hepatoma cells is also inhibited. A comparison with other liver-derived immunoinhibitors reported previously supports our claim that the liver-derived immunoinhibitory factor is a novel inhibitory protein. PMID- 1937392 TI - Kupffer cells from carbon tetrachloride-injured rat livers produce chemotactic factors for fibroblasts and monocytes: the role of tumor necrosis factor-alpha. AB - Conditioned media from cultured Kupffer and mononuclear macrophagic cells obtained 48 hr after CCl4 administration to rats contains chemotactic factors for human skin fibroblasts and human monocytes. The chemotactic mediator for fibroblasts was approximately 17 kD and was more prominent at early stages of culture. It induced a dose-dependent chemotactic response in fibroblasts. Although the conditioned medium from cultured Kupffer cells of normal rats also contained detectable biological activity, it was significantly less than that in conditioned medium from cultured Kupffer cells from CCl4-treated rats. The activity obtained after purification by high-performance liquid chromatography was completely ablated by incubation with tumor necrosis factor-alpha antibody. Transforming growth factor-beta antibody diminished biological activity by 20%. Human recombinant tumor necrosis factor-alpha and transforming growth factor-beta used in the assay as control showed significant chemotactic activity. The chemotactic activity present in whole normal conditioned medium was only present after 24 and 48 hr of culture. Furthermore, this activity was not neutralized by human recombinant tumor necrosis factor-alpha or transforming growth factor-beta antibodies. Incubation of whole 6-hr conditioned medium with human recombinant tumor necrosis factor-alpha and transforming growth factor-beta antibodies demonstrated and confirmed that tumor necrosis factor-alpha plays a major role in inducing the chemotactic response. On acidification of this supernatant, we found a notable increase in the biological response that could be neutralized by transforming growth factor-beta antibody. Thus tumor necrosis factor-alpha and transforming growth factor-beta may sequentially provide important signals for fibroblast and monocyte recruitment in vivo at initial stages of liver injury. PMID- 1937393 TI - Stimulation of putrescine production by epidermal growth factor in rat liver after partial hepatectomy. AB - When epidermal growth factor was given to rats after partial hepatectomy, hepatic putrescine content was significantly increased at 4, 6 and 10 hr compared with control rats. Ornithine decarboxylase activity was also increased. Hepatic ornithine decarboxylase messenger RNA content was significantly greater than control levels at 2 hr after epidermal growth factor treatment, but not at 10 hr, when the amount of ornithine decarboxylase messenger RNA in control animals was four times that at 2 hr. When actinomycin D was administered 6 hr after partial hepatectomy, hepatic ornithine decarboxylase activity at 10 hr was reduced to half the control levels. This reduction was attenuated by epidermal growth factor treatment at 6 and 8 hr. Hepatic immunoreactive ornithine decarboxylase protein content showed a highly positive correlation with hepatic ornithine decarboxylase activity at 4, 6 and 10 hr, irrespective of epidermal growth factor treatment. Hepatic spermidine N1-acetyltransferase activity was significantly increased at 6 hr compared with control rats. These results suggest that, after partial hepatectomy in rats, exogenous epidermal growth factor may stimulate hepatic putrescine production by increasing ornithine decarboxylase messenger RNA content and altering posttranscriptional ornithine decarboxylase regulation, as well as enhancing spermidine N1-acetyltransferase activity. PMID- 1937394 TI - Hepatotoxicity in a rat model caused by orally administered methotrexate. AB - We undertook a dose-response study in Wistar rats to develop an animal model for methotrexate hepatotoxicity. Rats were given oral methotrexate in 300, 200, 150 and 100 micrograms/kg/day doses for variable lengths of time. The 300 micrograms/kg/day dose produced systemic toxicity; the animals needed to be killed early, and hepatotoxicity was not observed. The lower doses of methotrexate were tolerated for longer durations and were associated with hepatotoxicity in five of the five rats receiving 200 micrograms/kg/day, four of the five rats receiving 150 micrograms/kg/day and five of the five rats on 100 micrograms/kg/day. Within each treatment group the liver injury ranged in severity from focal necrosis of some zone 3 hepatocytes to confluent necrosis of zone 3. All five rats that received 100 micrograms/kg/day methotrexate for 6 wk showed continuing liver injury in the form of focal necrosis, cell lysis and enlarged Kupffer cells. In addition, three of the rats showed evidence of early hepatic fibrosis. We believe that this is the first experimental model in which oral methotrexate administration has been associated with hepatotoxicity. Further development of this model should provide valuable insights into the pathogenesis of methotrexate hepatotoxicity. PMID- 1937395 TI - Transport of free fatty acid and triglyceride in anhepatic rats. AB - Without a liver the fractional plasma removal of free fatty acid is one third and chylomicron triglyceride one half of that in the intact rat. The intestine of the anhepatic rat converted enteral fatty acid to plasma triglyceride but was unable to do the same for plasma free fatty acid. This decrease in plasma free fatty acid removal and the inability to recycle the acid as triglyceride were, in part, responsible for the conversion of large fractions of plasma triglyceride flux to the plasma free acid in hepatectomized rats. Increased intravascular triglyceride lipolysis resulting from high circulating lipoprotein lipase concentrations and reduced plasma triglyceride removal were other factors shifting the partition of anhepatic plasma fatty-acid transport from the ester to the free. After the anhepatic plasma clearance of either free fatty acid or triglyceride, relatively more of both compounds was recovered in the lipid of actively metabolizing (heart and muscle) as opposed to storage (adipose) tissue when compared with controls. Sequential evaluations of the recovery of plasma free fatty acid and triglyceride in tissues of anhepatic rats demonstrated accumulation or storage solely in adipose tissue and only when the plasma fatty acid was in triglyceride. This observation and the large conversion of anhepatic circulating triglyceride to the free acid may, in part, explain the lack of an increase in adipose lipid with reduced hepatic mass. The data help explain the preferential use of a lipid fuel in liver disease and the difficulties in obtaining carbon storage in this condition. PMID- 1937396 TI - Conjugates of ursodeoxycholate protect against cytotoxicity of more hydrophobic bile salts: in vitro studies in rat hepatocytes and human erythrocytes. AB - Intraduodenal infusion of hydrophobic bile salts to bile-fistula rats leads within hours to severe hepatocellular necrosis and cholestasis; simultaneous administration of conjugates of ursodeoxycholate, either intraduodenally or intravenously, reduces or prevents liver injury. To evaluate the short-term protective effects of ursodeoxycholate at the cellular level, we incubated primary monolayer cultures of adult rat hepatocytes or freshly isolated washed human erythrocytes for 1 to 240 min with varying defined concentrations of different bile salts in the presence or absence of ursodeoxycholate. Cytolysis was quantified by measuring the release into the medium of cytosolic lactate dehydrogenase (hepatocytes) or hemoglobin (erythrocytes). In both systems, cytolysis increased sigmoidally with increasing bile salt concentration, and the relative toxicity of different bile salts proceeded in the following order: tauroursodeoxycholate was less toxic than taurocholate, which was less toxic than taurodeoxycholate. Taurochenodeoxycholate was more toxic to erythrocytes than taurodeoxycholate; the two were equally toxic to rat hepatocytes. Unconjugated bile salts were more toxic than their conjugates. The addition of tauroursodeoxycholate to taurochenodeoxycholate or taurodeoxycholate led to time dependent and concentration-dependent reduction or elimination of the toxicity of the more hydrophobic component. Protection was evident within minutes. With respect to hemolysis, at pH 8.5 glyco was less protective than tauroursodeoxycholate, and free ursodeoxycholate was only minimally protective. We conclude that the hepatocytotoxicity of hydrophobic bile salts at millimolar concentrations is markedly reduced in the presence of tauroursodeoxycholate. Conjugates of ursodeoxycholate also prevented disruption of erythrocytes by bile salts, suggesting that protection does not depend on liver-specific pathways of bile salt uptake, compartmentation, transport or metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937398 TI - Effect of age on liver protein synthesis and degradation. PMID- 1937397 TI - Fuel homeostasis and carnitine metabolism in rats with secondary biliary cirrhosis. AB - Energy metabolism is abnormal in patients and experimental animals with liver cirrhosis. To help better understand the abnormalities, fuel homeostasis and carnitine metabolism were studied in fed and 24-hr-starved rats with secondary biliary cirrhosis induced by bile duct ligation for 4 wk. Plasma ketone body concentrations were decreased by 67% in starved, bile duct-ligated rats compared with control rats. In contrast, plasma nonesterified fatty acid concentrations were not different between bile duct-ligated and control rats in the fed or the fasted state. Plasma triglyceride concentrations showed the expected decrease with starvation in control rats, but were increased with starvation in bile duct ligated rats. Urinary excretion of dicarboxylic acids was increased in both fed and fasted bile duct ligated-rats compared with the respective control groups. Compared with control rats, hepatic total carnitine content (per gram of liver) was increased by 24% in fed and by 36% in fasted, bile duct-ligated rats. Fed, bile duct-ligated rats had an increased short-chain acylcarnitine-to-carnitine ratio in liver, plasma and urine compared with control rats. Analysis of the hepatic coenzyme A pool showed decreased coenzyme A content in fed and fasted bile duct-ligated rats compared with control rats. Hepatic long-chain acylcarnitine and long-chain acyl-coenzyme A content increased with starvation both in control and bile duct-ligated rats. The rise in plasma nonesterified fatty acid concentration and hepatic long-chain acylcarnitine and long-chain acylcoenzyme A contents with starvation in bile duct-ligated rats are consistent with unaltered hepatic availability of fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937399 TI - Histological features of liver allograft rejection: do you see what I see? PMID- 1937400 TI - The influence of propanolol on portosystemic shunting. PMID- 1937401 TI - Loss of HBsAg after interferon-alpha treatment: cure of chronic hepatitis B virus? PMID- 1937402 TI - Reperfusion injury: a role for neutrophils. PMID- 1937403 TI - Is determination of the hepatic iron index of diagnostic value in patients with thalassemia minor and chronic alcoholic liver disease? PMID- 1937404 TI - Severe Legionella pneumophila infection in a patient with hairy cell leukemia in partial remission after alpha interferon treatment. AB - Legionella pneumonia is an increasingly frequently reported complication in immunocompromised patients, particularly patients with hairy cell leukemia (HCL) in active phase. The most important predisposing factor seems to be the quantitative and qualitative defect of the monocytic-macrophagic system characteristic of HCL. We report a case of severe Legionella pneumophila infection with multisystem involvement in a patient with HCL in stable partial remission obtained after therapy with interferon. In our patient recovery of a normal monocyte count did not protect against a legionella infection, indicating that this pathogen should always be sought in HCL patients even those in clinical and hematologic remission. Early diagnosis and appropriate treatment may reduce the mortality of this serious complication. PMID- 1937405 TI - Increase of serum interleukin-2 and regression of myeloma after rhGM-CSF treatment of drug induced bone marrow aplasia. AB - Recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) was administered to a patient with multiple myeloma (IgA, stage IIA) who had a chemotherapy-induced bone marrow aplasia with granulocytopenia complicated by severe pneumonia and septicemia. The rhGM-CSF was given as i.v. infusions, 300 400 micrograms daily, for three weeks. The patient responded both hematologically and clinically with improved granulocyte counts and clearance of massive pulmonary infiltrates. We also observed a partial remission of the myeloma with decreasing s-IgA levels and reduced plasma cell infiltration of the bone marrow during a period of up to four months after the rhGM-CSF treatment. Immunological studies performed during and after cytokine administration showed an increase in serum interleukin-2 (IL-2) levels and HLA-DR positive T-lymphocytes indicating an activation of the immune system. It is suggested that rhGM-CSF induced immunological changes which may have contributed to the partial regression of the myeloma. PMID- 1937407 TI - Radiotherapy as salvage treatment in patients with Hodgkin's disease or non Hodgkin's lymphoma relapsing after initial chemotherapy. AB - The prognosis of relapsing Hodgkin's disease (HD) and high grade aggressive non Hodgkin's lymphoma (NHL) is generally poor since many of these patients fail to respond to second line chemotherapy. Radiation therapy has been reported as an effective but seldom used, alternative treatment. We have observed very encouraging results with salvage radiotherapy in a highly selected group of eight lymphoma patients (six with HD and two with high grade NHL), suffering mainly from nodal relapse. The literature on the use of radiation therapy after chemotherapy failures in HD and NHL is reviewed. PMID- 1937406 TI - Ceftazidime and amikacin as empiric antibiotic therapy of febrile granulocytopenic patients with hematological malignancies. Report of 171 consecutive episodes. AB - One hundred and seventy-one consecutive febrile episodes occurring in 130 neutropenic adult patients with hematological malignancies (mainly acute leukemia) were empirically treated with a combination antibiotic therapy consisting of ceftazidime (100 mg/kg/day) + amikacin (15 mg/kg/day). Of these, 161 were evaluable. In the majority of episodes (75 per cent) documented infections were identified as a cause of fever. There were 73 bacteremias (34 Gram-negative, 29 Gram-positive, 10 polymicrobial). One third of patients had pneumonia. Cure without change of the initial regimen was achieved in 45/73 (62 per cent) bacteremic episodes and in 12/13 episodes of microbiologically documented infections without bacteremia. There were 35 clinically documented infections and 26 (74 per cent) of these were cured. Of the 40 patients presenting with possible infections 26 (65 per cent) were cured. Overall, cure without modification of the initial antibiotic combination was achieved in 109/161 episodes (68 per cent). In spite of the frequent occurrence of persistent neutropenia (82 per cent), the infectious mortality was low (8.6 per cent), and often due to superinfection. The deaths due to primary infections were 6/161 (3.7 per cent). Side effects were mild and rare. In our experience ceftazidime + amikacin was an effective and safe empirical regimen for this population of hematologic patients with persistent neutropenia and severe documented infections. PMID- 1937408 TI - Second malignant neoplasms in patients with non Hodgkin's lymphoma. AB - A retrospective review of the records of 3886 patients with non-Hodgkin's lymphoma registered at the Princess Margaret Hospital between 1970 and 1985 was undertaken to determine the incidence of second malignant tumours. Three thousand and twenty-one patients with a minimum documented follow-up of 6 months from referral were identified for analysis. The overall observed/expected ratio for all cancers in patients with malignant lymphoma was 1, suggesting no increased risk of developing a second malignant neoplasm compared to the general population. When the data were analyzed independently for each tumour site, statistically significant increased risk of developing acute non lymphocytic leukemia (ANLL) (p less than 0.001) and carcinoma of the tongue (p less than 0.05) were found. An increased risk of lung cancer following lymphoma was detected but was not statistically significant. Survival following diagnosis of ANLL and lung cancer was similar and significantly shorter than that following the diagnosis of other second malignancies. The risk of developing a second primary cancer was significantly related to increasing patient age. PMID- 1937409 TI - Pulmonary granulomatosis and angiitis. AB - A wide variety of disease processes, each requiring different therapy, may give rise to granulomatous and vasculitic pulmonary lesions, making accurate aetiological diagnosis essential. For this, adequate sampling of tissue is necessary, and this usually requires open lung biopsy in order to obtain sufficient material for microbiological, immunocytochemical and ultrastructural as well as histopathological investigation. Many cases diagnosed as lymphomatoid granulomatosis are examples of extranodal lymphoma. It is suggested that this is an inappropriate name and that such cases should be referred to as pulmonary lymphomas and the phenotype specified. PMID- 1937411 TI - The spectrum of bile duct lesions in end-stage primary sclerosing cholangitis. AB - Tissue from 15 livers with primary sclerosing cholangitis, obtained at transplantation, was examined histologically with respect to: small and medium sized bile duct lesions; large bile duct lesions; fibrosis/cirrhosis; and parenchymal changes. Lesions affecting small and medium-sized bile ducts were quantified by determining the percentage of 20 portal tracts involved. The two characteristic bile duct lesions of primary sclerosing cholangitis, periductal fibrosis and fibro-obliterative scars, were largely confined to medium-sized portal areas. Although present in each case, the number of such lesions varied considerably. Loss of bile ducts was the most conspicuous feature in small portal tracts where the diagnostic duct lesions of primary sclerosing cholangitis were rarely observed. Inflammation, ulceration and cholangiectases of large intrahepatic ducts were common, and appear to be useful additional diagnostic features. PMID- 1937410 TI - Abnormalities of differentiation and maturation in the oesophageal squamous epithelium of patients with tylosis: morphological features. AB - Tylosis is an autosomal dominant inherited defect of keratinization, associated in two Liverpool families with a high risk of developing oesophageal squamous carcinoma. In 29 individuals, followed by regular endoscopy and biopsy, we have noted several morphological abnormalities of the epithelium in this pre-cancerous condition. A control group of 43 non-tylotic patients with normal oesophageal histology and a further 26 patients with acute oesophagitis was used for comparison. Recognizable dysplasia was confined to the older age range in the tylotic group and was present in four patients. Almost half of the patients showed acute inflammation. Abnormalities of maturation were common, the most frequent being the presence of prominent basophilic inclusions and clear cell acanthosis, with parakeratosis and frank surface keratinization present in smaller numbers. There was, however, no statistically significant difference between the tylotic and inflamed control groups for any of these features. The only feature to show a significant difference between these groups was the presence of individual cell keratinization. The results suggest that in the oesophageal epithelium of the patients with tylosis, inflammation is the predominant abnormality, together with individual cell keratinization, and that these lesions appear in a much younger age group than dysplasia. PMID- 1937412 TI - Subacute cutaneous lupus erythematosus--the annular variant. A histological and ultrastructural study of five cases. AB - Subacute cutaneous lupus erythematosus is an uncommon, non-scarring variant of lupus erythematosus which has received scant attention in the pathology literature. Its recognition as a distinct entity is important, as, although mild systemic features may be associated, there is characteristically a relative absence of life-threatening renal or central nervous systemic involvement. Subacute cutaneous lupus erythematosus may be clinically sub-divided into the more common annular and the rarer papulosquamous (psoriasiform) variants. A clinicopathological study of five cases of the annular variant is presented with a review of the literature. We highlight the histological and ultrastructural appearances. Discriminatory features from the other variants of lupus erythematosus and additional conditions with which it may be confused, including lichen planus and acute graft-versus-host disease, are discussed. PMID- 1937413 TI - A comparative study of proliferation indices and ploidy in dysplastic naevi and malignant melanomas using flow cytometry. AB - Cell proliferation indices and DNA content have been determined in 18 intradermal naevi, 40 dysplastic naevi and 16 superficial malignant melanomas (less than 0.76 mm depth of invasion) using flow cytometry. In this study, proliferation indices of intradermal naevi and dysplastic naevi were not significantly different from each other. Abnormalities of DNA ploidy were not identified in the intradermal naevi or dysplastic naevi; whereas three of the malignant melanomas were aneuploid. In addition, cellular proliferation was increased within the group of malignant melanomas, in comparison with the naevi. This study has found no evidence to indicate that sporadic dysplastic naevi were more likely than intradermal naevi to transform to malignant melanoma, when objective criteria were employed. However, dysplastic naevi could be distinguished from some early malignant melanomas by absence of aneuploidy and by low cell proliferation indices. PMID- 1937414 TI - Localized herpes simplex lymphadenitis: report of three cases and review of the literature. AB - This report describes three cases of localized or regional herpes simplex virus lymphadenitis. Of the two patients who presented with inguinal lymphadenopathy, one had a localized rash prior to the development of lymphadenopathy, and the other developed a genital rash 2 days after lymph node biopsy. The third had occipital lymphadenopathy and concurrent localized occipital herpetic folliculitis. Localized herpes simplex virus lymphadenitis appears to be a specific clinicopathological entity. Histologically, it is characterized by varying degrees of follicular and paracortical hyperplasia, a prominent immunoblastic response and perinodal inflammation. Viral inclusions with or without focal necrosis in the lymph node may be seen, and immunostaining for viral antigen may be seen in paracortical cells. PMID- 1937415 TI - Oligodendrogliomas: a clinical, histological, immunocytochemical and lectin binding study. AB - We have studied 27 oligodendrogliomas with a panel of antibodies (vimentin, GFAP, S-100 protein, myelin basic protein, CAM 5.2) and of lectins (WGA, Con A, PNA, RCA, DBA, SBA) to different glycoproteins. There were 16 well-differentiated tumours, including one gliofibrillary and 11 anaplastic oligodendrogliomas, three of which were gliofibrillary. Four cases showed positivity for vimentin, three of which were anaplastic tumours. Fifteen cases were positive for S-100 protein (nine well-differentiated and six anaplastic tumours) and 13 contained GFAP positive cells (three well-differentiated and 10 anaplastic tumours). WGA binding was positive in 75% of well-differentiated and 63% of anaplastic oligodendrogliomas, the corresponding figures were 50% and 45% for PNA, 37% and 81% for Con-A and 25% and 54% for RCA. On the basis of the results with lectin binding, we believe that there are changes in the spectrum of tumour cell associated lectin-like proteins during malignant transformation. Our observations also suggest that the pattern of lectin expression can undergo substantial changes in the course of differentiation. PMID- 1937416 TI - Primary carcinoid of the testis in a 10-year-old boy. PMID- 1937417 TI - Vaginal metaplasia of the urothelium in two non-oestrogenized males. PMID- 1937418 TI - Non-secretory IgA kappa myeloma with distended endoplasmic reticulum: a case report. AB - A case of non-secretory multiple myeloma is presented. Plasma cells showed abundant cytoplasmic colloid contained in distended rough endoplasmic reticulum. Uniform cytoplasmic positivity for IgA heavy- and kappa light-chains was demonstrated with the immunoperoxidase staining technique. It is proposed that distension of the endoplasmic reticulum by immunoglobulin-related proteins is indicative of a block in their excretion or of the presence of active synthesis of the immunoglobulins or their subunits. PMID- 1937419 TI - So-called cutaneous lymphadenoma: a lymphotropic solid syringoma? PMID- 1937420 TI - Angiolymphoid hyperplasia with eosinophilia. PMID- 1937421 TI - Fibrosis of the appendix. PMID- 1937422 TI - Effects of presence of squabs upon plasma concentrations of prolactin and LH and length of time of incubation in ringdoves on "extended" incubatory patterns. AB - The effects of a brief exposure to newly hatched squabs upon the concentrations of plasma prolactin and LH secretion and length of incubation time in ring doves were investigated using a novel experimental procedure. After 5 days of incubation birds were deprived of their nests for 3 days. On return to their nests, the birds immediately resumed incubation and laid a second clutch of eggs after 5 days at which time the first clutch was removed. A consequence of this procedure was that at the time of hatching, concentrations of plasma prolactin had passed their peaks and were falling to baseline values, while concentrations of plasma LH were beginning to increase. This experimental manipulation made it possible to demonstrate that brief exposure to newly hatched squabs significantly affects the concentration of plasma prolactin, an effect which was more pronounced in females than in males. This increased secretion of prolactin was associated with a reduction of plasma LH which reached significance in females but not in males. Birds exposed to squabs spent a significantly longer period of time on their nests as compared to those birds not exposed to squabs. This observation is consistent with a role for prolactin in maintaining readiness to incubate. PMID- 1937423 TI - Passive immunization against chicken vasoactive intestinal polypeptide suppresses plasma prolactin and crop sac development in incubating ring doves. AB - Passive immunization of incubating ring doves with daily injections of sheep anti chicken vasoactive intestinal polypeptide (cVIP) serum prevented the proliferation of crop sac tissue observed in control doves given nonimmune serum. Daily injections of anti-cVIP serum did not prevent crop sac development in nonbreeding doves simultaneously treated with ovine prolactin. The concentrations of plasma prolactin were significantly depressed in birds given anti-cVIP serum although this effect became progressively less pronounced during the course of the 7- or 14-day treatment periods. Body weights and weights of regressed reproductive organs were unaffected by treatment with anti-cVIP serum and did not differ significantly from control birds. Doves showing a decreased prolactin response to anti-cVIP serum treatment developed an immune response to sheep serum which may have immunoneutralized the administered antibody. Concentrations of plasma LH were not consistently affected by anti-cVIP serum administration and were low throughout the study. The depression in plasma LH normally seen in females after their young hatch was not observed in females treated with anti cVIP serum. No effect of treatment was observed upon the birds' incubation behavior or in their readiness to feed and brood their young. These results suggest that in the ring dove, VIP is the physiological prolactin-releasing factor responsible for stimulating prolactin secretion and consequently the development of the crop sac, during incubation. They further indicate that increased concentrations of plasma prolactin may not be essential for gonadal regression or the maintenance of full incubation and brooding behavior in ring doves under laboratory conditions. PMID- 1937424 TI - Hormonal control of proceptive and receptive sexual behavior and the preovulatory LH surge in the ewe: reassessment of the respective roles of estradiol, testosterone, and progesterone. AB - When estrous behavior is induced in ovariectomized ewes by subjecting them to progestagen priming followed by a dose of estrogen large enough to guarantee estrus in all animals, an abnormally long period of estrus in induced, suggesting that the regime of steroid replacement needs modification. Using quantitative tests for proceptivity and receptivity, we studied the patterns of sexual behavior of intact ewes and then attempted to reproduce them in the same animals after they had been ovariectomized. We used various combinations of exogenous estrogen, androgen, and progestagen and compared the behavioral responses with an endocrine response, the preovulatory surge of luteinizing hormone (LH). In intact ewes, sexual behavior and the LH surge were closely synchronized and their characteristics differed slightly between the middle and the end of the breeding season. Proceptive behavior was not greatly affected by the frequency of tests, but the duration of receptivity was significantly reduced by frequent testing. In ovariectomized ewes, we found that: (a) progesterone priming is essential for normal patterns of receptive and proceptive behavior, and for synchronizing the behavioral and endocrine responses to estrogen; (b) androgens do not play a major role in the control of either receptive or proceptive behavior; and (c) the inclusion of a low dose of estrogen with the progestagen in the 'priming' regime improves the responses to estradiol-17 beta. Under these conditions, the timing, intensity and duration of the behavior are very close to those observed in the same ewes when they were intact and cycling spontaneously. PMID- 1937425 TI - The lack of influence of exogenous testosterone on male parental behavior in a neotropical frog (Eleutherodactylus): a field experiment. AB - Males of the Puerto Rican frog Eleutherodactylus coqui exhibit prolonged parental care (nest attendance and defense) of direct-developing eggs in nonaquatic nest sites. Earlier work showed that plasma androgen levels are significantly lower in males caring for eggs than in noncaring, calling males. In this study, we investigated the effects of elevated plasma androgens on parental care behavior by implanting either testosterone (T) or placebo (P) pellets in parental males brooding eggs in the field. Plasma androgen levels, assessed 4 days after pellet implantation, were six times higher in T males than in P males. Despite this increase, T males exhibited no changes in nest fidelity or brooding behavior. The results indicate that lower androgen levels, at least those corresponding to a decline in T during parental care, are not necessary to maintain parental behavior in this tropical frog. PMID- 1937426 TI - Adult partner preference and sexual behavior of male rats affected by perinatal endocrine manipulations. AB - Intact adult male rats, in which aromatization of testosterone to estradiol was prevented pre- and/or neonatally by ATD (1,4,6-androstatriene-3,17-dione), were repeatedly tested for partner preference behavior (choice: estrous female vs active male). In consecutive tests increasing preference scores for the female were found. Neonatal ATD males showed significantly lower preference scores for an estrous female than controls or prenatal ATD males. Prenatal ATD caused preference scores only slightly lower than those of controls. Ejaculation frequencies were markedly reduced or even absent in neonatal ATD males. Prenatal ATD treatment only had no or a moderately lowering effect on ejaculation frequency. Lordosis behavior of adult intact males was more facilitated following neonatal ATD treatment than following prenatal ATD treatment. In a number of tests the serotonergic drug 8-OH-DPAT was injected prior to testing for sexual partner preference and copulatory behavior. DPAT significantly increased preference for an estrous female in all groups of males when interaction was possible, but had no effect when sexual interaction was prevented by wire mesh. DPAT was able to increase the number of ejaculators in nonejaculating groups (i.e., perinatally ATD-treated males). "Premature ejaculations," i.e., ejaculations with the first intromission, were frequently observed with DPAT treatment in all groups of males. In conclusion, the availability of neonatal estrogen (derived from testosterone) organizes, at least partially, the preference for an estrous female normally shown by adult male rats. The lack of neonatal estrogen causes males to be less masculinized, both in partner preference behavior and ejaculatory behavior, and less defeminized in lordosis behavior.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937428 TI - The association between testosterone, sexual arousal, and selective attention for erotic stimuli in men. AB - Twenty-six, eugonadal men between the ages of 18 and 27 participated in this investigation of the relationship between sexual arousal, testosterone (T) levels, and the processing of sexual information. At each of the two test sessions, subjects gave a blood sample, listened to an erotic or neutral priming audiotape, and completed a dichotic listening task designed to assess selective attention for sexual stimuli. Subjective levels of sexual arousal to the audiotape and sexual attitudes and sexual experience were assessed by self-report measures. Contrary to our hypothesis, there was no relationship between levels of free T and the strength of the selective attention bias for sexual stimuli. However, men who were more distracted by the sexual material in the task reported higher levels of sexual arousal to erotic imagery than men who were less distracted by the sexual material in the task (P less than 0.01). Moreover, men who were more sexually aroused by the erotic audiotape made significantly less shadowing errors in the erotic prime condition then they did during the neutral prime condition (P less than 0.05). There was a negative association between T and shadowing errors in the erotic prime condition (P less than 0.05). These results suggest that lower thresholds for sexual arousal are associated with a greater bias to attend to sexual information and that T may have effects on cognitive-motivational aspects of sexual behavior by enhancing attention to relevant stimuli. PMID- 1937427 TI - The effects of intracranial implantation of estrogen on receptivity in sexually and asexually reproducing female whiptail lizards, Cnemidophorus inornatus and Cnemidophorus uniparens. AB - The ventromedial hypothalamus (VMH) is an important site in the neuroendocrine control of sexual receptivity in mammals. This study was conducted to determine if the VMH was also involved in estrogen induction of receptivity in whiptail lizards. Estradiol benzoate (EB) was implanted into the VMH of ovariectomized Cnemidophorus inornatus, a sexually reproducing species, and C. uniparens, a parthenogenetic species which displays "pseudosexual" behaviors similar to the sexual behaviors typical of both male and female C. inornatus. In both species, EB was significantly more effective in eliciting receptivity when implanted in the VMH than in other locations in the brain. These results support the idea that, as in mammals, the VMH is an important location of estrogen action in the control of receptive behaviors in both sexually and asexually reproducing whiptail lizards. PMID- 1937429 TI - Reciprocal relationships between pulsatile androgen secretion and the expression of mating behavior in adult male ferrets. AB - The pulsatile secretion of androgen was similar over a 12-hr period in breeding male ferrets implanted with jugular catheters which either achieved an intromission with an estrous female or received no socio-sexual contact. This negative result contrasts with the previous demonstration (Carroll, Erskine, and Baum, 1987, Endocrinology 121, 1349-1359) of a significant, delayed rise in mean plasma androgen concentrations in breeding male ferrets 5-12 hr after mating. Males used in that previous study had lower initial mean plasma levels of androgen and smaller testis diameters than the present males. We therefore asked whether differences in circulating androgen levels, characteristic of males in different phases of the seasonal breeding cycle, might affect the expression of mating behavior. Castrated males given 0, 0.2, 2.0, or 5.0 mg/kg of testosterone propionate (TP) showed dose-related increases in the expression of different components of sexual behavior, including neck gripping, mounting, and intromitting. Surprisingly, intromissive performance was significantly better in intact breeding males than in castrates given even the highest dosage of TP. These results suggest that ferrets' mating performance may vary with seasonal variations in androgen availability, and that the ability of males to exhibit a postcoital increase in the testicular secretion of androgen may be limited to the beginning or end of the breeding season, when circulating levels of androgen are relatively low. Mating-induced increments in androgen secretion at these times may enhance subsequent reproductive success by facilitating males' intromissive capacity, which is required for the induction of ovulation and optimal sperm transport in female partners. PMID- 1937430 TI - Facilitation of parental behavior in ring doves by systemic or intracranial injections of prolactin. AB - Systemic administration of ovine prolactin (PRL) has been previously reported to stimulate parental feeding behavior toward 7-day-old foster squabs by nonbreeding ring doves with previous breeding experience. The first of the present experiments reexamined this claim in experienced, nonbreeding birds given test squabs of different ages. Each visually isolated male and female dove was given twice-daily subcutaneous injections of ovine PRL or vehicle for 7 days and then tested for parental responses toward a single 1-3, 6-8, or 11- to 13-day-old foster squab. Prolactin significantly increased the incidence or frequency of parental regurgitation-feeding episodes in tests with all three squab age groups and, in addition, increased the incidence of parental feeding invitations (squab oriented bill openings) in tests with 6- to 8-day-old squabs. A second study explored the degree to which PRL can act directly on the central nervous system to facilitate parental activity in the absence of peripheral cues generated from PRL-induced changes in other target organs, such as those associated with crop sac growth and distension. In this experiment, 6- to 8-day-old test squabs were used to determine if parental behavior is enhanced by twice-daily intracerebroventricular (ICV) injections of PRL in doses below those required to stimulate peripheral target organs. Injection schedules and behavior testing procedures were the same as those used in Experiment 1. However, half of the ICV PRL-treated and ICV vehicle-treated birds were food deprived for 16 hr before and during the test in order to control for PRL-induced hyperphagia and resulting crop sac distension, which could confound the results by generating peripheral stimuli conductive to the display of regurgitation-feeding behavior. Intracranial injections of prolactin significantly increased the incidence of feeding behavior, parental feeding invitations, and crouching or sitting in the nest in food-deprived doves but not in freely fed animals. Empty crop sac weights of freely fed and food-deprived PRL-treated birds were not increased above control values, thus indicating that ICV PRL treatment did not result in significant stimulation of peripheral target organs. These results demonstrate a facilitative action of PRL on regurgitation-feeding responses and associated parental behaviors that is not restricted to squabs of one particular age range. They also indicate that PRL is capable of acting directly on the brain to promote these activities in the absence of PRL-induced changes in the crop sac and other peripheral target organs. PMID- 1937432 TI - AIDS and the hospice community. PMID- 1937431 TI - Some notes on the impact of treating AIDS patients in hospices. AB - As part of a larger nation-wide study of attitudes of hospice personnel, we incorporated questions about patient autonomy and economic justice in which we asked the respondents to share their beliefs about AIDS patients compared to patients terminally ill with other diagnoses. The convenience sample of 826 hospice workers, 76% of whom were clinical professionals (nurses, physicians, social workers) rated terminally ill patients and those with AIDS the same in terms of right to refuse life sustaining medical therapy. Although over one half believed that we are not currently spending enough on the care of AIDS patients, 25% thought that we spend too much on those terminally ill with other diagnoses. Issues of survival time, costs of care, and staff concerns about treating AIDS patients in hospices are briefly discussed. PMID- 1937433 TI - AIDS: experiences and attitudes of nurses from rural communities in Pennsylvania and New York. AB - In this study we determined rural nurses' educational preparation concerning AIDS, whether they thought their health care facilities and communities were prepared to care for persons with AIDS, their attitudes toward AIDS and homosexuality, and in what ways AIDS had or might affect their practice. A questionnaire, which included the Nurses' AIDS Attitude Scale (NAAS), was administered to 738 employed registered nurses in 9 rural counties in Pennsylvania and New York. Findings suggest that this sample held many negative attitudes towards AIDS and homosexuality and had specific educational needs, especially in the psychosocial domain. They thought rural physicians and health care facilities were not yet well prepared to care for persons with AIDS. PMID- 1937434 TI - Dying in prison: sociocultural and psychosocial dynamics. AB - In January 1988, an inmate-staffed hospice volunteer program began operation at a federal correctional medical facility, with the goal of meeting the unique psychosocial, palliative, and spiritual needs of terminally ill prisoners, primarily men with AIDS and cancer. This paper discusses sociocultural and psychosocial characteristics of the incarcerated patients and the prison hospital setting. It presents a number of case examples. Particular attention is given to the effect that an environment of intensified anger, hostility, distrust, and despair has on the coping mechanisms of terminally ill, incarcerated patients. PMID- 1937435 TI - The staging and monitoring by primary care providers of patients with human immunodeficiency virus infections. AB - As HIV testing expands through the population, primary care physicians will become more involved in the testing process. They will also be caring for increasingly larger numbers of HIV infected people from the asymptomatic through those with AIDS, through hospice care, should that become appropriate. This article summarizes key areas of clinician support for the HIV infected, clinical and laboratory markers associated with rapid progression of the disease, and important problem areas in clinical management. It also presents a series of staging diagrams that have proven useful in assisting clinicians in educating patients about the natural history of the HIV infection, the rationale for staging, the rationale for the timing of AZT therapy and Pneumocystis prophylactic treatment, and the significance of various prognosticators in management as the disease progresses. PMID- 1937436 TI - Grieving a loss from AIDS. AB - The determinants of the nature of an AIDS death and their likely effects on the survivors are identified. Specifically discussed with illustrative case examples are stigma, lack of social support, contagion, untimely death, protracted illness and disfigurement, and neurological complications. Strategies for intervention are suggested. PMID- 1937437 TI - AIDS in the workplace: implications for hospice programs. AB - AIDS presents health care providers with complex medical management issues as well as the need to confront their own fears and prejudices. Hospice programs provide specialized care to persons who are in the final stages of the disease. As the epidemic grows, they increasingly also must respond to HIV-infected staff. A comprehensive workplace program prepares the hospice provider for these challenges and ensures an appropriate response. The four essential elements of such a program are policy development, staff education, supervisory training, and compliance monitoring. Policies to consider include infection control, occupational exposure, confidentiality, and the response to HIV-infected patients and employees. Comprehensive education ensures quality care for AIDS patients. Particularly crucial is the education of managers and supervisors. After policy implementation and training, procedures must be instituted to monitor compliance and develop corrective action. A bibliography of additional resource materials is provided. PMID- 1937438 TI - The cost of caring for patients with HIV infection in hospice. AB - This article explores the organizational barriers that have limited the number of persons with AIDS cared for by hospice programs throughout the United States. The financial implications of caring for persons with AIDS are discussed and data from a survey of 15 hospice providers is presented. Examples of creative and cooperative coalitions among hospice programs and other community organizations that maximize scarce resources and share the financial burden of caring for those infected with HIV are presented as models. The diverse funding sources and individual hospice program decisions about palliative treatments and drugs and admission criteria highlight the difficulty of generalizing from the survey. PMID- 1937439 TI - A comparison of the psychosocial needs of hospice patients with AIDS and those with other diagnoses. AB - We compared the amount of psychosocial support required and received by patients with AIDS and without AIDS at Cedar Valley Hospice, Waterloo, Iowa. Hospice patients with AIDS (N = 11) required significantly more psychosocial support than non-AIDS patients (N = 36) of the same average age. The amount of non-hospice social support--family, congregation, and neighbors--received by AIDS patients was significantly less than that received by those with other diagnoses due to a virtual lack of neighbor support. There were no significant differences in family or congregational support. The high level of family support and lack of neighbor support may have been a result of many (8) of the AIDS patients having moved back to the area to die. A survey of hospice staff showed they felt working with AIDS patients was both more time consuming and more stressful than working with patients with other diagnoses. PMID- 1937440 TI - Family adaptation to AIDS: a comparative study. AB - In this study the McCubbin stress and coping model was used as a theoretical framework to compare the differences in family adaptation to AIDS and to other terminal illnesses. The non-probability convenience sample consisted of 26 families of AIDS patients and 26 of hospice patients with other terminal illnesses. The Family Inventory of Life Events and Changes was used to measure the number of stressful events experienced by the family since diagnosis and the Family Adaptation to Medical Stressors Questionnaire measured role flexibility. Families of AIDS patients had significantly more stress, more rules prohibiting emotional expression, lower trust levels, and more illness anxiety than the other families. PMID- 1937441 TI - Volunteers under threat: AIDS hospice volunteers compared to volunteers in a traditional hospice. AB - We studied volunteers in one of the world's first AIDS-dedicated hospices and compared them on demographic, experiential, and personality related dimensions to volunteers in a traditional hospice. Eighty percent of the active volunteers at each facility participated. Eight of 16 demographic and 4 of 11 personality related variables differentiated the two groups. AIDS hospice volunteers were on all measures a more heterogeneous group--largely gay or bisexual, younger, more likely to have had prior personal experience with AIDS. In addition, they perceived themselves to be functioning under a significantly higher degree of threat caused by their volunteer work. We performed a post hoc analysis controlling for sexual orientation and matching heterosexual volunteers for gender. Threats to health, social world, employment, and total threat significantly differentiated the two heterosexual groups of volunteers. PMID- 1937442 TI - Data watch. Home care used by 5.7 percent of households. PMID- 1937443 TI - Compensation, social trends alter hospital-MD relations. AB - Changes in physician compensation and social trends are ushering in a new era in hospital-physician group relations, according to experts. Physician payment reform, the shift toward managed care, ongoing primary care physician shortages, and the changing lifestyle preferences of younger physicians are helping to redefine hospital-MD relations for years to come. Still, some health care organizations are ahead of the curve on this issue. Meanwhile, what does it take to lure a city doctor to Weiser, Idaho? Some towns will do almost anything to recruit a physician. PMID- 1937444 TI - Community participation drives rural recruiting campaigns. PMID- 1937445 TI - Hospitals voice concerns over details of rural network plan. AB - In a broad new effort to stimulate rural hospital care delivery, the Health Care Financing Administration is funding demonstration projects that could "grow" health care networks in remote areas. But providers are cautious about participating in the Essential Access Community Hospital (EACH) program until final rules are published. PMID- 1937447 TI - Home health care agencies struggle with new federal rules. AB - The rules governing home health care are confusing, contradictory and expensive, say providers, and they're getting more so. But that doesn't mean the rules should be made lax, they argue. Some even look forward to quality enhancement as a by-product of new "outcome-oriented" Medicare surveys. Inevitably, home health care administrators agree, increased federal scrutiny has likely been spurred by the massive growth in the field in the past 15 years. PMID- 1937446 TI - Preventive measures key to sexual harassment policies. AB - While many employers have formal harassment policies, creating a workplace environment free from sexual harassment and hostility is quite another challenge. Both issues should receive serious attention from hospital executives who want to avoid having to defend harassment claims, say labor attorneys and hospital human resources experts. PMID- 1937448 TI - Computerized patient records goal of new group. PMID- 1937449 TI - CPR (computer-based patient record) concept--from the drawing board to reality. PMID- 1937450 TI - New mission statement creates system unity. PMID- 1937451 TI - CEOs: survival tips for the tough times ahead. PMID- 1937452 TI - Hardware could affect materials management IS. PMID- 1937453 TI - Fiber optics: health care needs a public network. PMID- 1937454 TI - Data watch. Tracking the long-term growth in outpatient care. PMID- 1937455 TI - Collaboration: hospitals find that working together is tough, rewarding--and vital. AB - When two Montana administrators worked together in the 1980s to eliminate duplicative services and technology in their community, competition was the name of the game. But times have changed, and collaboration is coming of age. Executives who have launched collaboration ventures say it was tough going but ultimately rewarding--and vital. PMID- 1937456 TI - Biotechnology drugs create new maze of concerns for hospitals. AB - Genetically engineered human insulin received federal approval nearly 10 years ago, but the pace of federal approval for new biotechnology drugs remains painstakingly slow. In any case, hospitals will soon face a multitude of financial, ethical and procedural issues surrounding these drugs. PMID- 1937457 TI - Clinicians struggle to stay up to date on practice parameters. AB - With hundreds of clinical practice parameters in place and hundreds more being developed, clinicians are scurrying just to keep up. But obtaining information on clinical guidelines ranks as a top priority for hospital quality management programs, according to an American Hospital Association survey. PMID- 1937458 TI - Hospitals offer wellness programs in effort to trim health costs. PMID- 1937459 TI - Knowing the score: rules of thumb for hiring in-house counsel. PMID- 1937460 TI - Blue Cross/Blue Shield plans adjust to competitive future. PMID- 1937461 TI - Vendor rivalry drives down hardware prices. PMID- 1937462 TI - Hospital CEOs, CFOs rate materials managers. PMID- 1937463 TI - Improving relations among RNs, MDs and CEOs. PMID- 1937464 TI - Acrosin, the peculiar sperm-specific serine protease. AB - The sperm enzyme acrosin has long been known as one of the key enzymes in the mammalian fertilization process. Elucidation of primary structures of preproacrosin from various species have allowed a deeper insight into the structural organization and the complex evolution of the sperm proteinase acrosin. In addition to the typical elements of serine proteases, the acrosin molecule possesses one novel domain that might convey DNA-binding properties. PMID- 1937465 TI - Proving paternity of children with deceased fathers. AB - Determination of paternity was attempted in the case of three children whose putative fathers are dead using DNA samples of the paternal grandparents. The DNA analyses were performed with both multilocus and single-locus probes which resolve highly polymorphic areas of human genome. The results were conclusive with both types of probes and facilitated, for example, the exclusion of the brother of the putative father. The evidence for true paternity obtained with DNA analyses can be considered reliable in this type of "indirect" paternity in which tests based on protein polymorphism are inconclusive. PMID- 1937466 TI - X-linked recessive chondrodysplasia punctata with XY translocation in a stillborn fetus. AB - A case of X-linked recessive chondrodysplasia punctata (CP) is described. The finding of a reciprocal X-Y translocation involving the region distal to Xp22.3 and the presence of fluorescent Yp11.23 regions confirms the localization of X linked recessive CP at p22.3. No gross peroxisomal abnormalities were present in the propositus. PMID- 1937467 TI - Cytogenetic studies in leprosy patients before and after chemotherapy. AB - The frequencies of chromosome aberrations and sister chromatid exchanges (SCEs), cell proliferation kinetics and mitotic indices were studied in peripheral blood lymphocyte cultures of leprosy patients both before and after chemotherapy. The differences in the frequencies of chromosome aberrations and SCEs between controls, paucibacillary and multibacillary patients were found to be statistically highly significant (P less than 0.001). The extent of cytogenetic damage seemed to depend on the severity of the disease. Lymphocytes of untreated leprosy patients showed a low mitotic index and a slow rate of cell proliferation. Following combined treatment with dapsone and rifampicin there was an increase, but to a lesser degree (P less than 0.01), in the frequency of SCEs and chromosome aberrations while the drug combination of dapsone, rifampicin and clofazamine had a nonmutagenic effect on chromosomes of the patient. Furthermore, after drug treatment, the cell proliferation rate and mitotic indices in paucibacillary patients were comparable to that of controls. These results indicate the clastogenic potency of Mycobacterium leprae and the remedial effects that follow therapeutic drug treatment. PMID- 1937468 TI - Cystic fibrosis allele frequency, sex ratio anomalies and fertility: a new theory for the dissemination of mutant alleles. AB - The observation that mothers of cystic fibrosis patients come from sibships that are larger than those of the fathers is explained by a decrease in sex ratio with increasing size of parental sibships. This feature also provides the basis for a new theory for the dissemination of the major mutant allele, deduced to have arisen 2,700-5,000 years ago, in accordance with an overall heterozygote advantage of around 3%. In heterozygous women with heterozygous partners, sex related selection probably occurs after fertilization. PMID- 1937469 TI - Cytogenetic and molecular characterization of a small ring chromosome in the complex karyotype of a girl with Turner syndrome. AB - Blood samples of an 8-year-old girl with Turner syndrome were examined using cytogenetic and molecular methods. Chromosomal analyses revealed a mosaic karyotype consisting of 25% 47,X,der(X), +r(X) and 75% 46,X,der(X) cells. Southern blot hybridizations with Y-specific DNA probes excluded a Y chromosomal origin of the small ring chromosome. In situ hybridization using DNA probe pXBR showed it to be X-derived. Examination of C-, Q-, and R-banding patterns indicated that the der(X) chromosome probably arose by a translocation event. PMID- 1937470 TI - A small deletion and an adjacent base exchange in a potential stem-loop region of the neurofibromatosis 1 gene. AB - A single-strand conformational polymorphism found in the DNA of a patient with neurofibromatosis 1 (NF1) was shown to be caused by a deletion of a CCACC or CACCT sequence and an adjacent transversion, located about 500 base pairs downstream from the region that codes for a functional domain of the NF1 gene product. This mutation could also be detected in the patient and in his affected daughter by heteroduplex analysis. The deletion removes the proximal half of a small potential stem-loop and interrupts the reading frame in exon 1. A severely truncated protein with a grossly altered carboxy terminus lacking one third of its sequence is expected to be formed from the mutant allele. PMID- 1937471 TI - Hypoxanthine-guanine phosphoribosyltransferase deficiency: analysis of HPRT mutations by direct sequencing and allele-specific amplification. AB - The Lesch-Nyhan syndrome is a severe X chromosome-linked human disease caused by a virtual absence of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity. A partial deficiency in the activity of this enzyme can result in gouty arthritis. To determine the genetic basis for reduction or loss of enzyme activity, we have amplified and sequenced the coding region of HPRT cDNA from four patients: one with Lesch-Nyhan syndrome (HPRTPerth) and three with partial deficiencies of HPRT activity, which have been designated HPRTUrangan, HPRTSwan and HPRTToowong. In all four patients, the only mutation identified was a single base substitution in exons 2 or 3 of the coding region, which in each case predicts a single amino acid substitution in the translated protein. Each base change was confirmed by allele-specific amplification of the patient's genomic DNA. It is interesting to note that the mutation found for HPRTPerth is identical to that reported for HPRTFlint. It appears that the two mutations are de novo events. PMID- 1937472 TI - Early preclinical diagnosis of dominant pseudoxanthoma elasticum by specific ultrastructural changes of dermal elastic and collagen tissue in a family at risk. AB - The preferred description for the Gronblad-Strandberg syndrome, pseudoxanthoma elasticum (PXE), refers only to the cutaneous aspect of the disease, although the skin is the least severely involved organ. The potential catastrophic manifestation of this heterogeneous heritable disorder is described in a dominant pedigree where mother and grandmother died because of major vascular problems. The family requested predictive testing of the three children. Diagnosis of PXE is usually performed by morphological examination of skin lesions, which reveal incrustations formed by inorganic ions (mainly calcium) and various organic (degraded?) materials in the elastin moiety of the elastic fibers. The ubiquitous elastic fibers in other organs and arteries may be similarly involved. Moreover, there is co-involvement of collagen fibrils at the electron microscopical level. The three adolescent siblings did not show any clinical PXE symptoms. However, ultrastructural investigation of overtly normal skin in predilection sites gave a positive diagnosis for this dominant PXE type. Dermal connective tissue showed a specific aberrant pattern: elastin of elastic fibers regularly contained small foci of calcification resembling those in perilesional skin of the mother and other PXE patients; in collagen bundles adjacent to altered elastic fibers, collagen fibrils occurred with thickened diameters and flower-like contours; ground substance material was increased. The possible pathogenetic mechanism and problems posed by predictive testing of adult-onset diseases are discussed. PMID- 1937473 TI - Three dimensional reconstruction of human pachytene spermatocyte nuclei of a 17;21 reciprocal translocation carrier: study of XY-autosome relationships. AB - A study of XY-autosome relationships at the pachytene stage in an infertile 17-21 reciprocal translocation carrier was undertaken by means of three dimensional reconstruction. Synaptonemal complexes and the sex vesicle were analysed on electron microscopic serial sections and the reconstruction was performed on transparent sheets and on a Samba 2000 (Alcatel TITN) image analysis system. All asynapsed segments were entirely included in the sex vesicle, the chromatin fibre of the autosomes and sex chromosomes being tightly intermingled. In one nucleus, the four arms of the quadrivalent were paired, except around the breakpoints where an interstitial asynapsis was observed. In the other nuclei, a terminal asynapsis involving one or two arms of the quadrivalent was found. In the sex vesicle, autosomal asynapsed segments showed the same morphological characteristics as those of X and Y chromosomes. This observation agrees with the hypothesis of the extension of gene inactivation from sex chromosomes to autosomes. PMID- 1937474 TI - Substitution of Ile-172 to Asn in the steroid 21-hydroxylase B (P450c21B) gene in a Finnish patient with the simple virilizing form of congenital adrenal hyperplasia. AB - The steroid 21-hydroxylase enzyme (P450c21) is a member of the cytochrome P450 gene superfamily and is essential in the synthesis of cortisol and aldosterone. Defects in the P450c21B gene cause congenital adrenal hyperplasia (CAH), a common genetic disorder leading to virilization of newborn females. To avoid the standard cloning of mutant P450c21 genes from genomic libraries, we amplified the full-length genomic P450c21 genes by polymerase chain reaction (PCR). The amplification was followed by cloning and sequencing of a defective P450c21B gene. The strategy described here is generally applicable, thus making a simple characterization of the complete P450c21B gene possible. The method was tested in one patient suffering from the simple virilizing form of CAH. The sequence of three independent clones originating from the defective P450c21B showed that Ile at position 172 in exon 4 was substituted by Asn. The identical mutation also has been found in other patients with CAH. PMID- 1937475 TI - Information content of the Centre d'Etude du Polymorphisme Humain (CEPH) family structures for linkage studies. AB - This paper derives theoretical values for joint polymorphism information content for two markers from a family structure consisting of four grandparents, two parents, and many offspring. These data determine the efficiency of linkage map construction. PMID- 1937476 TI - Mitochondrial DNA mutation in an Italian family with Leber hereditary optic neuropathy. AB - Mitochondrial (mt) DNA from a Southern Italian family with Leber hereditary optic neuropathy was analyzed for the presence of the reported mutation at position 11778 of the ND4 subunit gene. The point mutation was found in mt DNA extracted from peripheral blood in all members of the family with the exclusion of the father, and was present in a homoplasmic fashion, despite the phenotypic heterogeneity of disease presentation among family members. PMID- 1937477 TI - A rapid and simple electrophoretic method for the detection of mutations involving small insertion or deletion: application to beta-thalassemia. AB - The 1.8-kb beta-globin gene fragments of DNAs from individuals heterozygous for nine different beta-thalassemia mutations involving 1, 2, 3, 4, or 25 basepair (bp) insertions or deletions were amplified by the polymerase chain reaction (PCR). The PCR products were subjected to electrophoresis on aqueous 8% polyacrylamide gel. In each heterozygote with either a 2 to 25 bp deletion, but not with a 1 bp insertion, two slower migrating bands representing heteroduplexes in addition to the 1.8-kb homoduplex band were seen. The electrophoretic positions of these slower migrating bands were characteristic of each mutation studied. By co-amplification with known normal DNA, it was also possible to distinguish DNAs from normal individuals and from individuals who are homozygous for the small insertion/deletion mutations. These studies demonstrate that the heteroduplex formation generated in PCR can be applied as a simple method in the diagnosis of insertion/deletion mutations involving 2 to 25 bp in beta thalassemias as well as in other genetic disorders. PMID- 1937478 TI - Sister chromatid exchange (SCE) frequencies differ between directly prepared cytotrophoblasts and cultured mesenchymal core cells. AB - Analysis of sister chromatid exchange (SCE) in chorionic villus cells may become useful in measuring the response of fetal tissues to clastogens or mutagens or for prenatal diagnosis of chromosome breakage syndromes such as Bloom syndrome. Previous studies have failed to analyze cytotrophoblastic cells and mesenchymal core cells, or have found no difference between SCE frequencies in directly prepared and cultured cells. Our data indicate significant differences in SCE frequencies between the two cell types: SCE frequency in directly prepared cytotrophoblasts was 6.73 SCE/cell +/- 1.6, whereas SCE frequency in cultured mesenchymal core cells was 10.31 SCE/cell +/- 0.49 (P less than 0.001). SCE analyses involving chorionic villi must take into account cell type. PMID- 1937480 TI - Rapid detection of alpha-1-antitrypsin deficiency by analysis of a PCR-induced TaqI restriction site. AB - A single base substitution is responsible for the PI-Z mutation in alpha-1 antitrypsin (AAT) deficiency. The Z mutation, which is in exon V of the AAT gene, was analysed directly using a primer designed with a single base substitution in the DNA sequence. During the polymerase chain reaction with this primer, a restriction enzyme site was created in the exon-V-amplified DNA sequence; this site was present in the normal allele (M form) but absent in the Z form. Here, the design of the primer and the application of the designer primer for prenatal diagnosis of chorion villus samples (CVS) for AAT deficiency is described. The method provides a simple rapid means of prenatal diagnosis of AAT deficiency within a day of the collection of the CVS. The detection of the nucleotide base change in AAT deficiency at the Z mutation site provides the opportunity for accurate prenatal diagnosis where no tissue is available from an AAT-affected individual. PMID- 1937479 TI - Analysis of 14 cystic fibrosis mutations in five south European populations. AB - We have analysed five Southern European populations (Albanian, Greek, Italian, Spanish and Yugoslavian) for 14 cystic fibrosis (CF) mutations. The most frequent mutations, apart from delta F508, were G542X (6.04%), R1162X (3.61%) and N1303K (3.24%). Each of the other analysed mutations were present at a frequency of less than 1% (R347P, R334W, S549RA, S549I, G551D, R553X and W1282X), and four mutations (D110H, delta I507, S549RT, and S1255X) were not found in this sample. The data presented here allows the use of mutation analysis in 69.5% of Spanish, 58% of Greek, and 56.5% of Italian CF cases. PMID- 1937481 TI - A new definition of genetic distance. AB - A stochastic measure of genetic distance between populations is proposed; unlike currently used measures, it is invariant with respect to union and subdivision of loci. This measure enables a unified quantitative approach to genetic diversity within populations and genetic distance between populations. PMID- 1937483 TI - MAC (morphology antibody chromosomes) technique for in situ chromosome preparations. PMID- 1937482 TI - A case of Hirschsprung disease with a chromosome 13 microdeletion, del(13)(q32.3q33.2): potential mapping of one disease locus. AB - A mentally retarded boy with discrete physical findings, Hirschsprung disease (HD) and a microdeletion of 13q,del(13)(q32.3q33.2) is described. Band 13q33.1 was consistently missing in all cells. There have been, to date, 4 published cases of deletions involving the long arm of chromosome 13 associated with HD: the interstitial deletion reported here is much smaller than, and it partially overlaps with, the previously reported deletions; it could be helpful for mapping one of the genes involved in this disease. PMID- 1937484 TI - Multiple sutural synostosis and congenital cataracts. PMID- 1937485 TI - Frequency of the cystic fibrosis mutation delta F508 in Algeria. PMID- 1937486 TI - Hereditary disorders in Saguenay-Lac-St-Jean (Quebec, Canada). AB - Saguenay-Lac-St-Jean is a geographically isolated region located in northeastern Quebec. Opened to the white settlement in 1938, its immigrants mainly came from Charlevoix, another isolated region of Quebec. The prevalence and/or incidence of several autosomal dominant and recessive disorders are very high. The overall birth prevalence of the recessive disorders was calculated at 1/207 living births and the overall carrier rate at 1/7 inhabitants. This situation may be explained by migration and social factors. PMID- 1937487 TI - Association between the acid phosphatase 1 and adenosine deaminase systems in a Brazilian sample. AB - Analyses of pairwise associations between several erythrocyte genetic systems were performed on a sample from a Brazilian trihybrid population. The present paper confirms the association between the ACP1 and ADA loci, the acid phosphatase 1 and adenosine deaminase systems. The results indicate that both selection and racial admixture may influence this association. PMID- 1937488 TI - Impact of heredity in myopia. AB - A series of 109 like-sexed twin pairs in the age group 30-31 years (54 monozygotic and 55 dizygotic) with one or both members of the twins with myopia was found in the Finnish Twin Cohort. The series was based on a random sample of 1,200 twins in one age stratum of the cohort. The twins received a questionnaire on their health status with special reference to eye diseases and symptoms. The refractive status of the twin pairs was ascertained by asking the twins to send their latest prescription for glasses to the authors or the refraction was obtained from the ophthalmologists or opticians of the twins. The mean difference in refraction between the monozygotic twins was 1.19 dptr in the right eyes and 1.15 dptr in the left eyes. The difference between dizygotic pairs was 2.34 dptr in the right eyes and 2.47 dptr in the left eyes. Analysis of variance showed that the difference in refraction between the two eyes of a twin pair was not significant. The mean difference in refraction between the monozygotic twins was significantly lower than that between dizygotic twins (p less than or equal to 0.001). The intrapair variances were doubled among dizygotic twin pairs compared to monozygotic twin pairs in the male group. The intrapair variance in the female group was 4-fold among dizygotic twin pairs as compared to monozygotic twin pairs. Heritability of myopia was 0.58 (0.74 for males and 0.61 for females) when myopia was considered a dichotomous variable. This result suggests that inheritance has a substantial effect on the etiology of myopia. PMID- 1937489 TI - Population studies in northern Sweden. XVII. Estimates of Finnish and Saamish influence. AB - The North-Swedish population is a mixture of Finnish, Saamish and Central-Swedish ethnic groups. We have studied the Finnish and Saamish admixture by means of genetic markers in 23 North-Swedish subpopulations. The Finnish influence was estimated using the transferrin genes B0-1, DCHI and C3 and the enzyme gene SOD1*2, and markers for Saamish influence were the blood group gene ABO*A2, the serum group gene GC*1F and the enzyme gene 6PGD*C. In the subpopulations the Finnish influence (admixture) varied between 0 and 84% and the Saamish influence between 0 and 34%. The Saamish influence was strongest in the western and northern parts of the area. In the northern part of the area, between 1/4 and 1/3 of the gene pool of the present-day population may be Saamish in origin. The Finnish influence was strongest in the northern and northeastern parts of the area. In the subpopulations along the Finnish border, between 60 and 80% of the gene pool may be Finnish in origin. Significant correlations were found between the Saamish marker genes and between the Finnish marker genes. Due to geographical overlapping of Finnish and Saamish influence, significant correlations were also found between Finnish and Saamish marker genes. The geographical pictures of Saamish and Finnish influence in northern Sweden showed a fair agreement with the expectations derived from historical knowledge. Although a substantial part of the genetic heterogeneity of the North-Swedish population is ethnic in origin, it is obvious that founder effect and genetic drift also have played an important role. PMID- 1937490 TI - Founder effect in familial hyperchylomicronemia among French Canadians of Quebec. AB - Familial hyperchylomicronemia has reached a high prevalence in the French Canadian population of eastern Quebec. The birth places of 58 carriers identified through the birth of one affected child clustered in three regions. The genealogies of these 58 individuals showed that no founder was common to all of them. Three sets of founders were found, one for each region, with little overlapping between two regions. These results strongly suggest that more than one mutation, introduced by the French migrants in the 17th century, are segregating in the French Canadian population. Perche, a region situated between Paris and Normandy, appeared to be the most likely putative center of diffusion of at least one mutation in the lipoprotein lipase gene segregating in the modern day French Canadian population of Quebec. PMID- 1937491 TI - Forensic applications of molecular genetic analysis: an Italian collaborative study on paternity testing by the determination of variable number of tandem repeat DNA polymorphisms. AB - Several variable number of tandem repeat (VNTR) DNA polymorphisms detecting different loci (YNH24/MspI or TaqI, CMM101/MspI or MLJ14/MspI, EFD64.2/RsaI or HinfI, YNZ22/TaqI, AW101/EcoRI, EKMDA2.1/PvuII and 3'-HVR/PvuII) were used in the analysis of 27 cases of disputed paternity in the Italian population. Fourteen exclusions and 17 attributions were performed. The results were compared with those obtained with immunohematologic analyses. Four exclusions and 2 attributions were made possible only by the combined use of several DNA polymorphisms, as the analyses of red-blood-cell antigens and isoenzymes, serum proteins and HLA group determinants were inconclusive. With the DNA test, 10 exclusions and 15 attributions were confirmed, with increased overall probability. In conclusion, VNTR polymorphisms were more informative, accurate and sensitive than the immunohematologic tests. Therefore, DNA analysis is the method of choice for testing genetic relationships. PMID- 1937492 TI - Segregation distortions of the ABO and Rh systems in malformed newborns. AB - This study compares the segregation of the ABO and Rh systems between malformed newborns and a control group with two purposes: (1) to evaluate the participation of genetic factors associated with these blood groups in the production of congenital malformations, and (2) to prove, indirectly, the existence of reproductive losses associated with congenital malformations. The newborns and their mothers were typed for ABO and Rh groups. Gene frequencies were similar in malformed and control newborns. In the female malformed newborns, an excess of O B pairs and a deficit of B-B pairs in the ABO system, and an excess of Rh(-)-Rh- pairs in the Rh system were found. PMID- 1937493 TI - Transferrin types in different ethnic groups of the USSR and Mongolia. AB - Transferrin (TF) subtypes were studied in 7 different populations from the Soviet Union (Buryats, Russians, Koreans, Kirghizes and Pamirians) and in 3 different populations from Mongolia. The frequency of the C2 gene varied between 10.4% in Pamirians and 27.4% in Koreans and was generally higher in populations of Mongoloid origin. The frequency of the C3 gene was found to be very low (nonpolymorphic) in the Mongoloid groups, but it was also low (1.5%) in Russians. Rare B and D variants were found in 7 populations. The highest D frequencies were found in the Mongoloid populations. PMID- 1937494 TI - Polymorphism of complement component I in Mongoloid populations: a new genetic variant IF A2. AB - The genetic polymorphism of the complement component I (IF) was investigated in 282 Chinese, 239 Koreans and 198 Japanese. The 3 common IF phenotypes (A, AB and B) and a new rare IF phenotype (BA2) were observed. The obtained allele frequencies are as follows: IF*A = 0.0993 and IF*B = 0.9007 in Chinese; IF*A = 0.0921 and IF*B = 0.9079 in Koreans; IF*A = 0.0985, IF*B = 0.8990 and IF*A2 = 0.0025 in Japanese. These 3 Mongoloid populations showed a much higher degree of IF polymorphism than Caucasian populations. PMID- 1937495 TI - Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies in patients treated with the mouse monoclonal antibody 17-1A (ab1). Relation to the clinical outcome--an important antitumoral effector function? AB - Forty-three patients with metastatic colorectal carcinoma (CRC) were treated with the unconjugated mouse monoclonal antibody (MAb) 17-1A (ab1) only. The presence of antiidiotypic antibodies (ab2) and anti-antiidiotypic antibodies (ab3) were analyzed using an ELISA technique and a mixed hemadsorption assay respectively. Ninety-five percent (41/43) of the patients developed ab2 both of the IgM and the IgG classes. Forty-seven percent (20/43) of the patients had detectable ab3 after therapy, two of them also before administration of MAb 17-1A. Binding in vitro of ab3 (ab1) to CRC cells could be specifically inhibited by ab1. Ab3 bound to human monoclonal antiidiotypic antibodies and to a goat antiidiotypic antibody (ab2). Both these ab2 were directed against MAb 17-1A (ab1). There was a strong correlation between the presence of ab3 and the clinical outcome. Ab3+ patients survived significantly longer than those who did not develop ab3 antibodies, 80 weeks vs 38 weeks (p less than 0.001). A statistically significant correlation was found between the presence of ab3 and the anti-tumor response (CR + PR + MR + SD) (p = 0.01). Thus, induction of an antiidiotypic cascade seems to be an important antitumor effector function of MAb in the treatment of cancer patients. PMID- 1937496 TI - Characterization of a monoclonal antibody against P57, the C3/C3b-cleaving proteinase expressed in human erythrocyte membranes. AB - A monoclonal antibody was raised against p57, a serine proteinase, characterized by an apparent molecular weight of 57 kDa, and purified from human erythrocyte membranes. P57 proteinase cleaves the human third component of complement, C3. The antibody selected, MP1, of IgG2a isotype, precipitated specifically the p57 antigen which carried the C3/C3b-cleaving activity present in membrane crude extract of human erythrocytes. P57 proteinase eluted from MP1-sepharose was inhibited by 5 x 10(-4) M PMSF, enhanced by 0.5% SDS and generated C3 fragments identical to those generated by membrane crude extract of human erythrocytes. All these properties were identical to those of the p57 previously purified by biochemical procedures. In addition, 5000 binding sites were detected on cell surface. This MP1 monoclonal antibody will be helpful to analyse the role of p57 in human erythrocytes. PMID- 1937497 TI - Production and characterization of monoclonal antibodies to Ha-ras and N-ras p21. AB - The mammalian ras family consists of the Ha, Ki and N-ras genes that encode a series of 21,000 dalton proteins (p21). The three ras proteins participate in normal cell physiology and have been implicated in cellular transformation by either overexpression of the normal p21 or by mutation at positions 12, 13, or 61. To help understand the biological roles of the different ras proteins, we have generated monoclonal antibodies (Mabs) to the Ha-ras and N-ras p21. Mab Ha 770, raised to a Ha-specific synthetic peptide, reacts with Ha-ras recombinant p21 (r-p21) as well as cellular Ha-ras p21 by immunoprecipitation. Western blot and sandwich ELISA assays. Mab N-838, raised to an N-ras specific synthetic peptide, reacts with the N-ras recombinant p21 by immunoprecipitation, Western blot and sandwich ELISA assays. Mabs to the Ha-ras and N-ras p21 should be valuable reagents in assessing the individual roles of ras proteins in normal and neoplastic cells. PMID- 1937498 TI - The 200/220 kDa antigen recognized by monoclonal antibody (MAb) UJ127.11 on neural tissues and tumors is the human L1 adhesion molecule. AB - MAb UJ127.11, raised against 16 week human fetal brain, recognizes an antigen present primarily on normal and tumor tissues derived from the neuroectoderm. The antigen has previously been identified as a 220/240 kDa cell surface glycoprotein as determined by immunoprecipitation studies. We show here, that the 220/240 kDa antigen is the human L1 cell adhesion molecule and by Western blot analysis actually has a calculated molecular weight of between 200-220 kDa. Immunocytochemical studies with UJ127.11 and an antibody (5G3) recently utilized to isolate human L1 from brain indicate that both reagents have very similar binding profiles. The binding of radiolabelled UJ127.11 to its target antigen can be blocked by the addition of a rabbit anti-human L1 antiserum. Furthermore, sequential immunoprecipitation and Western blot analysis shows that UJ127.11 and the rabbit anti-human L1 antiserum recognize identical proteins. PMID- 1937499 TI - Generation of monoclonal antibodies to bovine follicle-stimulating hormone and application in an enzyme immunoassay. AB - Twenty monoclonal antibodies (MAbs) to bovine follicle-stimulating hormone (bFSH) were generated by using the hybridoma technique. Twelve of the MAbs have been shown to bind specifically to bFSH and seven of them were purified from the respective ascitic fluids with the methods of caprylic acid precipitation and hydroxylapatite column chromatography. The purity of the MAbs was in the range of 86-95%. Three of the purified MAbs have been coupled to horseradish peroxidase (HRP). By using a matrix cross-matching procedure, two MAbs reacted with discrete antigenic determinants are selected for a double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA). The designed ELISA procedure could be performed within 60 min in a two-stage incubation and has a minimum sensitivity of 1ngFSH/ml. For serum samples, its mean intra- and inter-assay coefficients of variation were 3.4% and 7.3% respectively. The DAS-ELISA can be used to establish a complete FSH profile in the field of in vitro diagnosis. PMID- 1937500 TI - Binding characteristics of monoclonal antibodies raised against bovine growth hormone. AB - Monoclonal antibodies have been raised against pituitary bovine growth hormone using the hybridoma procedure. The binding characteristics of the seven selected monoclonal antibodies toward the antigen molecule in its native, chemically or enzymatically treated form have been studied. The reactivities of the monoclonal antibodies with growth hormones from other species and bovine prolactin have also been investigated. The epitopes recognized by four of the produced monoclonal antibodies are conformational, whereas two other monoclonal antibodies bind to sequential determinants. Three antibodies define immunological sites located between residues 6-124 of the bovine growth hormone molecule, and one of this antibody shows higher affinity to human than bovine growth hormone. The immunoreactivity of one monoclonal antibody is enhanced by the previous binding of the antigen to polyclonal antibodies, probably because of a localized conformational change of the bovine growth hormone molecule. This antibody also shows cross-reactivity with all the homologous hormones tested, indicating to recognize a highly conserved antigenic determinant. PMID- 1937501 TI - Monoclonal antibody against sheep kappa light chain. AB - The production of a monoclonal antibody specific for sheep kappa light chain protein is described. The monoclonal antibody was designated McM11 and its specificity was verified using western blots of sheep IgG and slides of efferent lymph cells. The specificity of McM11 was confirmed by specific recognition of fusion proteins expressed by recombinant phage containing sheep kappa cDNAs. N terminal sequence of the light chain recognized by McM11 showed homology to kappa type light chains. McM11, together with McM6, a lambda specific monoclonal antibody, was shown by two color FACS analysis of sheep blood lymphocytes to recognize all sheep light chains. PMID- 1937502 TI - Mink-mouse interspecific hybridomas. AB - Mink-mouse interspecific hybridomas were produced by fusion of the american mink spleen cells with the NSO cells. Seven cloned lines of the mink-mouse hybridoma were isolated, and their functional mink Ig secretion and karyological characteristics are given. During cytogenetic analysis of mink-mouse hybridoma cell lines, we observed the elimination of mink chromosomes, and inter- and intralineral variability of the numbers of the cells with particular quantities of mink DNA. We did not find that the characteristic peculiarities of mink DNA distribution in the hybridoma cell lines had any bearing upon the secretion or non-secretion of mink Ig. There was no synthesis of lambda-L-chains of mink Ig in line 7 cells because the line lost the lambda-gene. With the aid of in situ hybridization with 3H-labeled total mink DNA, a considerable transformation of hybridoma cell karyotype was observed. Multiple integration of the mink DNA into mouse chromosomes and the appearance of chromosomes not characteristic for either the mink or mouse parent cells were noted. Increasing numbers of cells with translocations of mink chromosomes fragments into mouse chromosomes were found in the hybridoma lines cultivated for lengthy periods. PMID- 1937503 TI - Isolation of hybridoma forming cells from immune spleens by unit gravity sedimentation. AB - In 1975 a method for the production of hybridomas that secrete monoclonal antibodies was first described (1). Since that time, surprisingly little information has emerged on the identity of the fusible spleen cell. In this report we describe the isolation of hybridoma forming cells from immune spleens and the enrichment of B cell populations in different states of activation. The B cells that reside in immune spleens are comprised of heterogeneous populations that differ in their states of activation. These populations have been difficult to separate and, therefore, difficult to characterize. Two factors that discriminate B cells in different states of activation are cell size and density. Unit gravity sedimentation is a simple, reliable and reproducible method for separating cells based on their size and density. Immune B cells were fractionated on a 10 to 25% serum gradient at unit gravity. Cells were collected and pooled, when necessary, to perform functional assays. Fractionated B cells were assayed for hybridoma formation, PFC response, Ig secretion and proliferation. The cells that exhibited hybridoma formation, PFC activity and Ig secretion were all found in the large cell fractions that comprised less than 10% of the cells recovered from the gradient. Proliferating B cells were found primarily in smaller cell fractions compared to antibody forming cells. Resting B cells were located in the smallest cell fractions recovered from the gradient. Data show that separation of immune B cells by unit gravity sedimentation is an effective means to isolate hybridoma forming cells and enrich for B cell subpopulations in different states of activation. PMID- 1937504 TI - Measurement of human red blood cell deformability using a single micropore on a thin Si3N4 film. AB - The filtration method for the evaluation of the RBC deformability has been further refined to simulate the deformations encountered in the recticuloendothelial system (in particular the spleen), a recognized site of aged and sickled cells removal. The core of the developed measuring system is a very thin (0.4 micron thick) filter that consists of single micropore (diameters down to 1 micron) on a Si3N4 film which has been constructed using silicon microfabrication techniques. Individual RBC's deformability is quantified measuring the cell pore passage time. From one blood sample 200 passage times are analyzed by a computer, displaying mean and median values as deformability indexes, and class and cumulative histograms for studying the passage times distribution. In this paper the effectiveness of the developed system as a routine clinical evaluation tool is demonstrated by studying several factors that are known to affect the RBC deformability, such as temperature, addition of diamide and glutaraldehyde, and blood storage conditions. In addition, it is experimentally demonstrated that the human RBC can traverse a pore with a diameter as small as 1 micron when the pore length is very short, thus broadening the experimental conditions under which the RBC deformability (fluidity) can be studied. PMID- 1937505 TI - Ultrasonic interferometry: study of particle sedimentation in liquid. AB - An ultrasonic interferometry method was designed to study sedimentation of particles in liquid. The method, based on A mode echography, measures the amplitude of ultrasonic waves reflected (echo E1) by a fixed interface I1 called "solid plate-sediment" interface formed when particles are sedimenting on a solid plate. The amplitude of the echo depends both on mechanical properties of the three media (solid plate, sediment and suspension) on the thickness of the sediment and on the presence of a second mobile interface I2 called "sediment suspension" interface. In the first phase of sedimentation when the second interface is very close to the first, two reflected waves interfere. Then, in the second phase of sedimentation when the sediment is thick enough, the amplitude of the echo E1 depends only on the sediment and solid plate properties. The first phase will give information on the sedimentation rate of particles (SR). We have compared SR of particles determined by this method with SR measured in a cylindrical tube of the same geometry as the ultrasonic measurement cell and with theoretical values of the sedimentation rate given by theoretical models. PMID- 1937506 TI - An ultrasonic method for measuring tissue displacement: technical details and validation for measuring myocardial thickening. AB - We have developed a method for measuring myocardial thickening from a single ultrasonic transducer attached to the epicardium. Displacement of the underlying myocardial tissue is measured by following the phase of the echoes within a sample volume range-gated across the myocardium. The output is in the form of an analog signal. To verify the accuracy, resolution, and limitations of the system, we derived the equations relating the position of a reflector to the phase of its echo and compared the system output in vitro to a known input using a single moving target and a random distribution of scatterers, and in vivo to that of an ultrasonic transit-time dimension gauge. The results demonstrate that the 10 MHz system can accurately follow the motion of single or multiple targets with a resolution of 0.02 mm. In 25 dogs myocardial thickening measured with the displacement system compared favorably in both waveform and magnitude with thickening measured by the two-crystal transit-time method. Applications for the displacement method include: quantification of regional ventricular function in animal models of cardiovascular diseases, measurement of endocardial to epicardial differences in the deformation of regional myocardium during the cardiac cycle, and evaluation of regional cardiac function in patients during and after corrective cardiac surgery. PMID- 1937507 TI - Monitoring of the ballistocardiogram with the static charge sensitive bed. AB - The static charge sensitive bed (SCSB) consists of a sensitive movement detector embedded in a mattress. When a subject rests on the bed, a single electrical signal, containing components reflective of cardiac, respiratory, and body movement related motion, is produced. This paper describes a digital signal processing technique to separate the BCG from the SCSB signal. An evaluation of this algorithm was conducted using recordings from normal volunteers. Comparisons with simultaneously recorded reference signals indicated that the algorithm performed satisfactorily in a laboratory environment. PMID- 1937508 TI - New noninvasive transcutaneous approach to blood glucose monitoring: successful glucose monitoring on human 75 g OGTT with novel sampling chamber. AB - A novel noninvasive and quasi-continuous method of transcutaneous blood glucose monitoring for use with the human 75 g oral glucose tolerance test (OGTT) has been developed. The effused fluid was obtained by applying suction on the skin surface and labeled suction effusion fluid (SEF). The system consists of two main parts: a suction apparatus and the glucose sensor system. The suction apparatus applies vacuum to the patient's skin at 400 mmHg absolute pressure to collect the SEF. The miniature ion sensitive field effect transistor (ISFET) based glucose sensor can measure glucose in small SEF quantities. The monitoring system is based on the association between the glucose concentration in the SEF and in the serum. During the 75 g OGTT, the glucose change in the SEF was measured every 10 min. Although a response delay of up to 20 min was observed in the SEF glucose change, it was possible to perform the 75 g OGTT by this noninvasive monitoring method. PMID- 1937509 TI - A silicon-based, three-dimensional neural interface: manufacturing processes for an intracortical electrode array. AB - A method has been developed for the manufacture of a "three-dimensional" electrode array geometry for chronic intracortical stimulation. This silicon based array consists of a 4.2 x 4.2 x 0.12 mm thick monocrystalline substrate, from which project 100 conductive, silicon needles sharpened to facilitate cortical penetration. Each needle is electrically isolated from the other needles, and is about 0.09 mm thick at its base and 1.5 mm long. The sharpened end of each needle is coated with platinum to facilitate charge transfer into neural tissue. The following manufacturing processes were used to create this array. 1) Thermomigration of 100 aluminum pads through an n-type silicon block. This creates trails of highly conductive p+ silicon isolated from each other by opposing pn junctions. 2) A combination of mechanical and chemical micromachining which creates individual penetrating needles of the p+ silicon trails. 3) Metal deposition to create active electrode areas and electrical contact pads. 4) Array encapsulation with polyimide. The geometrical, mechanical, and electrical properties of these arrays should make them well suited as interfaces to cortical tissue. PMID- 1937510 TI - Muscle recruitment with intrafascicular electrodes. AB - We have studied muscle recruitment with Teflon-insulated, 25 microns diameter, Pt Ir intrafasicular electrodes implanted in nerves innervating the gastrocnemius and soleus muscles of cats. The purpose of this study was to measure the performance of these bipolar electrodes, which had been designed to optimize their ability to record unit activity from peripheral nerves, as stimulating electrodes. Recruitment curves identified the optimal stimulus configuration as a biphasic rectangular pulse, with an interphase separation of about 500 microseconds and a duration of about 50 microseconds. The current required for a half-maximal twitch contraction was on the order of 50 microA. Current and charge densities needed for stimulation were well below levels believed to be safe for the tissue and electrode materials involved. When the spinal reflex pathway was interrupted by crushing the nerve, the force produced by a given stimulus changed in some cases, but not in others, implying that the spinal reflex contribution was not the same in all the implants. We conclude that intrafascicular recording electrodes are also a potentially valuable technology for functional neuromuscular stimulation, and warrant further development. PMID- 1937511 TI - Clustering analysis and pattern discrimination of EMG linear envelopes. AB - A technique has been developed for performing pattern analysis of EMG activities generated during locomotion. In this development it was found that the shapes of the EMG linear envelopes (LE) are mainly determined by their phase spectra; their magnitude spectra are much less important. Autoregressive (AR) parametric models and discrete Fourier transform (DFT) approaches were tested and compared. The latter was proved to be a better way to describe the EMG LE's. Feature extraction and clustering were performed by doing DFT of EMG LE's, extracting part of the phase and magnitude spectra (in less important degree) as features, and using the percent powers to weigh the corresponding harmonics. The approach was applied to the clustering analysis of EMG LE's of normal and anterior cruciate ligament (ACL) injured subjects during walking. PMID- 1937512 TI - Applications of adaptive filtering to ECG analysis: noise cancellation and arrhythmia detection. AB - Several adaptive filter structures are proposed for noise cancellation and arrhythmia detection. The adaptive filter essentially minimizes the mean-squared error between a primary input, which is the noisy ECG, and a reference input, which is either noise that is correlated in some way with the noise in the primary input or a signal that is correlated only with ECG in the primary input. Different filter structures are presented to eliminate the diverse forms of noise: baseline wander, 60 Hz power line interference, muscle noise, and motion artifact. An adaptive recurrent filter structure is proposed for acquiring the impulse response of the normal QRS complex. The primary input of the filter is the ECG signal to be analyzed, while the reference input is an impulse train coincident with the QRS complexes. This method is applied to several arrhythmia detection problems: detection of P-waves, premature ventricular complexes, and recognition of conduction block, atrial fibrillation, and paced rhythm. PMID- 1937513 TI - A mathematical model of overall cerebral blood flow regulation in the rat. AB - In the present work a mathematical model of the cerebrovascular regulatory system in the rat is presented. The model, a generalization of our previous one, includes the reactivity of proximal segments of the cerebrovascular bed and the neurogenic and myogenic feedback regulatory mechanisms besides the action of chemical regulatory factors. The model is then used to analyze the interaction of mechanisms regulating cerebral blood flow in several conditions of physiological importance. In the first stage of the work we simulated experiments in which the neural fibers are cut and artificially stimulated with external means. According to experimental evidence, simulation results point out the existence of an escape of blood flow from stimulation. The model imputes this escape phenomenon to the antagonistic action of chemical factors working on the distal segments of the cerebrovascular bed. In a second stage, we studied the neurogenic mechanism action in a physiological closed-loop condition. With this general model, autoregulation to arterial pressure changes and postischemic reactive hyperemia have been analyzed. A comparison of simulation results with recent experimental data shows that the model is able to produce 60-70% of the experimental regulatory capacity of the cerebrovascular bed. However, some relevant discrepancies still exist between the model and the experimental results, especially as regards the dilatory capacity of small cerebral arterioles. These discrepancies underline the existence of further regulatory mechanisms working on the cerebrovascular bed, the nature of which must still be clarified. PMID- 1937514 TI - Postural stability and stereo-ambiguity in man-designed visual environments. AB - Our modern rectilinear visual environment contains visual stimuli for which evolution has not had time to optimally shape visual processing. One such stimulus, periodic stripes, is known to lead to visual depth ambiguity. In this paper we show that postural instability, as measured by the variance of fore and aft sway, is increased by viewing such stimuli. This instability may be the precursor of falls. Designers must evaluate the visual impressions conveyed by their systems in order to avoid postural instability due to visual ambiguity. PMID- 1937515 TI - The use of modified constellation graph method for computer-aided classification of congenital heart diseases. AB - This paper describes a new method of data reduction and classification in a multidimensional symptom space for diagnostic aid of congenital heart diseases. The algorithm developed here is to reduce interactively a multidimensional symptom space to sectorial regions representing each disease in a semicircle using the modified constellation graph method. This method enables us to classify patients using the angle in the semicircle as a single classifying parameter with an accuracy of about 90%, that is, with little overlapping between disease sectors. Comparing this method with conventional factor analysis, we have found the former far more effective than the latter for disease region separation. PMID- 1937516 TI - On nets... PMID- 1937517 TI - Women at risk: an AIDS educational needs assessment. AB - In order to acquire the information nurses need to develop education and support programs for women at risk for Acquired Immunodeficiency Syndrome (AIDS), a qualitative needs assessment of women at risk was conducted. Interviews were conducted with 21 women who were at risk for AIDS through their own injection drug use or as the heterosexual partners of injection drug users. Results were analyzed using the variables of the Health Belief Model, including the concept of self-efficacy. The perception of AIDS as a serious and a personal health threat motivated these women to practice both "safe sex" and "safe drug use." However, they did not always believe that recommended health behaviors would be effective; and they noted significant costs associated with these behaviors. In addition, the impact of AIDS was seen to be a heightening of the isolation and mistrust which were characteristic of the injection drug using community before the epidemic. AIDS programs for women at risk should facilitate discussion of social and community issues and should emphasize hope rather than fear. PMID- 1937518 TI - Career-oriented women with tattoos. AB - Almost 50 percent of all tattoos are being done on women, many of whom are counselors, nurses, doctors, lawyers and business managers. Career-oriented women (N = 137) who had tattoos for at least six months were surveyed in a national study. Consequences associated with the unconventional, permanent product- purchase risk (pain, expense, inexperience), possession risk (self, family and general society response) and health risks--were examined. Women obtained tattoos as an expression of individuality. Almost no elements of purchase or health risks were reported, but possession risk occurred. Strong support for the tattoo was expressed by the significant person in the women's life and friends, while mild support was perceived from mothers, siblings and children. Respondents cited a lack of, or negative response from their fathers, physicians, registered nurses and the general public. Misunderstanding of what a tattoo means to the individual and stereotyping of women with tattoos continues. Understanding career-oriented women's experience of seeking tattoos may provide a new gender/cultural perspective which has implications for health care professionals. In addition, nursing may have a role to play in educating tattoo artists about health care risks. PMID- 1937519 TI - Medication calculation ability of registered nurses. AB - A convenience sample of 110 registered nurses in four western states completed a demographic questionnaire and a 20-item medication calculation test to investigate errors in medication calculation that contribute to medication error rates. Intravenous questions were most difficult, then oral, then intramuscular/subcutaneous items. Nurses erred more when more than one calculation was required and when milligram to grain conversion was needed. Nurses who rated their skill and comfort with medication calculation above average scored higher. Yet 81 percent of the nurses were unable to correctly calculate medications 90 percent of the time and 43.6 percent of the test scores were below 70 percent accuracy. Strategies are suggested which may be used in staff development in identify registered nurse medication calculation abilities and to enhance these skills in practicing nurses. PMID- 1937520 TI - Knowledge of medical terminology among clients and families. AB - This descriptive correlational study replicated Byrne and Edeani's (1984) investigation of hospitalized clients' (N = 25) knowledge of 50 common medical terms. The present study also included 25 family members. The mean number of correct responses was 46 (of 50) with no difference between clients and families. Only nine terms were correctly understood by all respondents. Older persons with higher education and moderate length of illness had higher scores. Participants in the present study scored significantly higher than those in the prior research especially on terms related to breast cancer and heart disease. Clients and family members may not understand medical terms as well as nurses think they do and may need consistent assessment of knowledge in the context of patient teaching. PMID- 1937521 TI - Medication regimen complexity and adherence among older adults. AB - Two studies were conducted to examine the relationship between medication regimen complexity and adherence among older adults recently discharged from hospitals (N = 178) and those not recently hospitalized (N = 98). Medication regimen complexity was measured by the Medication Complexity Index (Kelley, 1988), which measures the number, frequency, and types of actions required to enact a medication regimen. Adherence to the regimen was measured by pill count and verbal self-report. The negative correlations between regimen complexity and adherence were in the predicted direction but did not achieve statistical significance. Medication regimen complexity may have a larger impact on aspects of medication management other than adherence to the prescriptive regimen. PMID- 1937522 TI - A taxonomic structure for the concept comfort. AB - The concept of comfort is an important one for nursing, but because of its complexity, it has not been analyzed, operationalized or structured for nursing science. In this paper, three technical senses of the term are derived from: (a) contemporary and archaic lexical entries; (b) analysis of how the concept is used in contemporary and historical nursing literature; and (c) theoretical support found in the disciplines of nursing and ergonomics. Next, the contexts of patients' needs are explored and four contexts are derived from the nursing literature on holism. When the three senses and the four contexts of needs are juxtaposed, a 3 x 4 grid with 12 elements emerges that encompasses the total domain of patient comfort. Each element describes an aspect of comfort from which empirical indicators, antecedents, consequents and test items can be developed. The grid represents a taxonomic structure of the concept that organizes the meanings of this complex concept. The structure can be used to develop comfort pretests as the nurse assesses possible needs in a given situation and to develop comfort post tests, to assess the effectiveness of comfort measures. PMID- 1937523 TI - Legal methodology as nursing problem solving. AB - This article presents legal methodology as a form of nursing research. The four elements of the legal methodology are examined. The sources of legal authority are explained and the essential components of one case, Sermchief v Gonzales are presented in detail as an illustration of the legal methodology. In addition to the elements of the methodology, the methodological tools for the process are described. The computer and manual searching strategies are identified. Finally, the citation system which serves as an integral portion of the methodological process is discussed. PMID- 1937524 TI - Story as link between nursing practice, ontology, epistemology. AB - This paper proposes the use of story as a method of organizing and communicating nursing knowledge which assures groundedness in the ontology of nursing. The nursing situation is viewed as the unit of nursing knowledge, and the nursing story is the re-creation or representation of that situation. PMID- 1937525 TI - Women and HIV infection. PMID- 1937526 TI - Another look at hardiness. PMID- 1937527 TI - A thesis is born. PMID- 1937528 TI - The dialogue concerning caring. PMID- 1937529 TI - T-cell recognition of bacterial heat-shock proteins in inflammatory arthritis. PMID- 1937530 TI - Is there a role for mycobacteria in the etiopathogenesis of rheumatoid arthritis? PMID- 1937531 TI - Regulation of mycobacterial heat-shock protein-reactive T cells by HLA class II molecules: lessons from leprosy. PMID- 1937532 TI - Do stress proteins play a role in arthritis and autoimmunity? PMID- 1937533 TI - Cell death mechanisms and the immune system. AB - The immune system provides good models for cell death, a phenomenon now recognized to be of fundamental importance in many fields of biology. Cell death is strikingly polymorphic: it can proceed via necrosis (as in complement-mediated cell death) or apoptosis, but the latter displays different patterns (in the receptor-mediated death of some thymocytes, in cell death mediated by TNF alpha or by cytotoxic T cells), perhaps reflecting different pathways of control of a common core mechanism. Even though there are differences in the morphological and metabolic changes associated with the different patterns of apoptosis, some recurrent sequences of events are observed in almost all dying cells. The metabolic state of a cell often seems to play a major role in determining if and how this cell will die in given external circumstances. The nature of molecules causally involved in the dying cell can now be approached in some systems. PMID- 1937534 TI - Heat-shock proteins as immunogenic bacterial antigens with the potential to induce and regulate autoimmune arthritis. AB - Heat-shock proteins are ubiquitous and surprisingly immunogenic bacterial proteins. Due to their extensive evolutionary conservation, development of immune reactivity directed at hsp is expected to jeopardize the maintenance of tolerance for "self". The experimental model of adjuvant arthritis in rats has been illustrative in this respect. In this model disease is induced by immunization to mycobacteria, and by T-cell cloning it appeared that T cells with specificity for the 180-188 sequence of the mycobacterial hsp65 were capable of both inducing the disease or inducing resistance to the disease. Although the exact molecular mimicry relationship of this 180-186 epitope with the proteoglycan moiety of cartilage remains to be elucidated, the crucial significance of hsp65 immunity has been substantiated further, not only in adjuvant arthritis, but also in other models of experimentally induced arthritis. Development of disease is seen to coincide with development of hsp65 reactivity, and in AA to the 180-186 epitope in particular. There is now experimental evidence that responses to hsp65 are subject to regulatory T-cell control, and that such regulatory control may explain the observations that preimmunization with hsp65 induces protection against subsequent development of arthritis. In human arthritis, responses to hsp65 have been seen to occur at the level of synovial fluid-derived T lymphocytes. Especially, in children with juvenile chronic arthritis such responsiveness was seen to be directed at the endogenous "self" hsp60, as it was also found to be expressed at a raised level in the synovial lining cells. Altogether, both from the experimental models and from the human disease, evidence is being collected for hsp65 as a critical antigen which has, in the experimental models, the potential of inducing protective regulatory T-cell control. AA has now offered us some initial possibilities for exploiting this feature of hsp65 in inducing remission of disease. We may hope that, ultimately, such specific immunological intervention in disease will also become a reality in the management of human autoimmune arthritis. The exploitation of the regulatory control mechanisms that normally contain the dangerously autoimmune reactive elements in the system seems to be most attractive for such a purpose. We should not try to modify the outside non-self; however, we should use our understanding of the mechanisms involved in order to stimulate the immune system of the unfortunate to resume control over the management of responses directed at the endogenous "self". It is possible that further analysis of the role of hsp65 in arthritis will lead to such necessary understanding. PMID- 1937535 TI - Heat-shock protein 60: implications for pathogenesis of and protection against bacterial infections. AB - In this review we have focused on antigenic features of hsp 60 related to: its ubiquitous distribution in the biosphere; its extraordinary homology among various bacteria; its high conservation from prokaryotic to eukaryotic cells; and its abundant expression under stress situations occurring during infection. These unique features make hsp 60 an excellent candidate antigen relevant to protection and pathogenesis of bacterial infections and, perhaps in a broader sense, to surveillance and autoimmunity. We will briefly discuss these possibilities in the following. Acquired resistance. If we assume that bacterial organisms contain some thousand different proteins which all represent potential antigens, the frequency of T cells with specificity for mycobacterial hsp 60 appears surprisingly high. Although, during the course of infection, high levels of hsp may be induced in bacteria, mere abundance appears to be an important though insufficient explanation. In addition, constant boosting by similar hsp 60 cognates from various microbes with which humans come into contact may contribute to dominance. This could easily explain the occurrence of hsp 60-specific T cells in healthy individuals with no clinical history of mycobacterial infections. Involvement of more sophisticated mechanisms, such as the affinity of hsp to other proteins, cannot be excluded (Flynn et al. 1989). Yet dominance does not necessarily mean protection and definite proof that hsp are protective antigens is lacking. Perhaps the immune response against epitopes shared by various mycobacterial pathogens represents a first line of defence preceding a more specific immune response. Such broadly reactive antigens would not qualify as prime candidates for vaccine design. Immunesurveillance. T cells with specificity for epitopes shared by bacterial and human hsp 60 are readily demonstrable and stressed host cells are recognized by hsp 60-specific T cells. Such T lymphocytes are endowed with the capacity to identify host cells stressed by a variety of assaults such as inflammation, infection, trauma, or transformation. Although it has been claimed that hsp-reactive gamma/delta T cells are particularly destined for such surveillance functions (Born et al. 1990, Asarnow et al. 1988), alpha/beta T cells could also participate. Pathogenesis. The mechanisms causing pathogenesis should be similar to those underlying protection and surveillance. In the former case bacterial hsp would be responsible for both induction of immunity and expression of pathogenic reactions; in the latter case an immune response stimulated by conserved regions of bacterial hsp 60 would be converted against a host-derived cognate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1937536 TI - Role of hsp60 during autoimmune and bacterial inflammation. PMID- 1937537 TI - Transgenic mice and immunological tolerance. PMID- 1937538 TI - A transgenic approach to the study of peripheral T-cell tolerance. AB - There is now convincing evidence for the imposition of self tolerance by means of the clonal deletion of self-reactive T cells operating within the thymus. Since not all self components may be encountered there, the question must be asked whether tolerance can occur post-thymically. To test this, we and other investigators have used transgenic technology to direct expression of a known "nonself" gene to a given extrathymic tissue. No lymphocytic infiltration was ever seen in transgene-expressing tissues, even if the mice were given normal syngeneic (nontransgenic) spleen cells intravenously or were stimulated with H 2Kb spleen cells. Infiltration did, however, occur in irradiated transgenic recipients of H-2Kb immune spleen cells. In MET-Kb mice, this infiltrate diminished with time, raising the possibility that peripheral tolerance may even have been induced in immune cells. H-2Kb-bearing skin was accepted in young RIP Kb mice but rejected in older mice, which had lost more than 75% of their beta cells as a result of the overexpression of H-2Kb. This loss of tolerance thus occurred when the concentration of the tolerogen, H-2Kb, fell below some critical threshold. Following in vitro stimulation, spleen cells from young RIP-Kb mice could not kill H-2Kb-bearing targets, but could respond to third party targets. Thymus cells, on the other hand, could be stimulated to kill both targets, clearly indicating that tolerance was not imposed intrathymically. Spleen cells from older RIP-Kb mice (those that had lost most of their beta cells) killed both targets, which is in agreement with the in vivo data. Reactivity to H-2Kb was restored to young spleen cells by providing them with IL-2. Two hypotheses were proposed to account for the above findings: tolerance results either from the deletion or functional silencing of high-affinity effector cells or of regulatory, IL-2-producing helper T cells. As it is difficult to distinguish between these, we have produced a second series of transgenic mice (F3+) with rearranged TCR genes encoding an anti-H-2Kb TCR and derived "double-transgenic" (F3+RIP+) offspring by mating these mice with RIP-Kb mice. The transgenic TCR utilized the V beta 11 segment which can be detected by a monoclonal antibody. There were in the thymus very few CD4+ and very few CD4+8+ cells in both F3+ and F3+RIP+ mice and, in the double-transgenic mice, there was no evidence of deletion of CD8+V beta 11+ cells in the periphery although they showed tolerance to H-2Kb-bearing skin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1937540 TI - T and B cell tolerance and responses to viral antigens in transgenic mice: implications for the pathogenesis of autoimmune versus immunopathological disease. AB - Experiments with transgenic mice illustrate clonal elimination of T cells specific for antigens expressed appropriately in the thymus, but presence of inducible T cells when the antigen presented on class I MHC antigens is expressed exclusively on non-lymphohemopoietic cells in the periphery (pancreatic beta islet cells). TCR-transgenic LCMV-carrier mice expressing LCMV in the thymus exhibit clonal elimination at the early CD4+8+ thymocyte stage, causing CTL unresponsiveness in these mice. In contrast, studies with RIP LCMV-GP-transgenic mice (expressing GP in pancreatic beta cells) and with TCR-RIP LCMV-GP double transgenic mice show that CTL reactivity is normal. These experiments argue against so-called peripheral anergy of class I MHC antigen-restricted cytotoxic T cells as a general mechanism of peripheral immunological tolerance to self. They reveal that self epitopes that are genetically self and presented by class I antigens may not be considered immunologically self if expressed solely extrathymically, despite the fact that they are antigenic and can be recognized by induced effector T cells. Genetic self that is presented on cells which can induce neither tolerance nor an immune response is immunologically dealt with as foreign and therefore may be called nonimmunological self. Appropriate presentation of the same epitope on antigen-presenting cells promptly induces effector T cells and causes disease; such disease should not be called autoimmune because it is an immunopathological T-cell mediated disease, comparable to an unfavorably balanced immunopathological T-cell response to a virus. Mechanisms that control autoantibody responses were studied in mice expressing a viral transgene. Such mice generate neutralizing antiviral autoantibody responses only when the transgenic viral antigen is linked to a foreign T-helper determinant. These findings, therefore, document differences in levels of T- vs B-cell tolerance (so-called split tolerance) under a given expression level of a "self" antigen. They illustrate how unresponsiveness of B cells to produce T-independent IgM is dose-dependent and that IgG autoantibodies are triggered by introducing foreign T-helper determinants that can be recognised in a linked fashion. This model suggests that, while T-cell tolerance to tolerogenic self in the thymus is solid, B-cell tolerance in general is not. From the point of view of autoantibody responses these T-helper cells may also be called immunopathological; i.e., these T-helper cells are specific for foreign epitopes that, via linked recognition, trigger truly autoimmune B cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1937539 TI - Clonal deletion of autospecific B lymphocytes. AB - Using mice transgenic for functional, rearranged immunoglobulin heavy and light chain genes, it can be demonstrated that B lymphocytes reactive with cell surface bound class I MHC antigen can be controlled by clonal elimination. Even low affinity cell-bound ligands can induce deletion. Deletion can occur in the pre-B to B cell transitional stage or after the B cells exist the bone marrow, depending on where the cells first encounter autoantigen. IgD appears to play no role in protecting cells from deletion. It is argued that defects in B-cell tolerance alone may be sufficient to lead to systemic autoimmunity. PMID- 1937542 TI - Transgenic mice with ectopic expression of alloantigenic MHC molecules--why are they so different and of how much help are they? PMID- 1937541 TI - Immunological self-tolerance: an analysis employing cytokines or cytokine receptors encoded by transgenes or a recombinant vaccinia virus. PMID- 1937544 TI - Self tolerance in the B-cell repertoire. PMID- 1937543 TI - Tolerance to liver-specific antigens. AB - We have described a TG model for peripheral tolerance of alloreactive CTL. Expression of Q10/L on hepatocytes renders mice functionally tolerant, although in vitro we observe that TG animals have normal numbers of CTL.Pf directed against this antigen. The basis for the tolerance presumably resides in the fact that the TG mice are lacking a subpopulation, either through deletion or anergy, that is responsible for recognition of the antigen on hepatocytes in vivo. The data are consistent with a tolerance model where cells with high affinity receptors are silenced. The presumed low affinity antigen-specific cells remaining in TG mice cannot be primed in vivo when immunized with antigen on spleen cells. Further, these CTL generate poor lytic activity in vitro. This failure to prime TG CTL in vivo could be attributed to primed cells traveling to the liver where they become tolerized when exposed to antigen on hepatocytes. However, we show that TG cells, after transfer to non-TG recipients, cannot be primed in vivo, indicating that the presumed low-affinity cells remaining in TG mice are not readily activable in this milieu. These data also indicate that this tolerance is not readily reversible during a 10- to 17-d time interval. PMID- 1937545 TI - Low dose, oral lorazepam: a safe and effective adjuvant to antiemetic therapy. AB - Twenty-five patients with acute nonlymphoblastic leukemia undergoing 41 cycles of chemotherapy with daunorubicin/cytosine arabinoside (ara-C) or with etoposide/ara C received metoclopramide (MCP; 0.5 mg/kg 6 hourly i.v.) or MCP (same dose) plus oral lorazepam (1 mg/d) during and 24 hours following the chemotherapy as antiemetic medication. Control of vomiting was achieved is 55% (complete 5%, partial 50%) of the patients receiving MCP alone and in 100 percent (complete 76.1%; partial 23.8%) of those receiving MCP plus lorazepam (p less than 0.001). Eighteen of the 21 patients (85.7%) receiving MCP plus lorazepam opted for the same antiemetic regimen as compared to six of the 20 (30%) receiving MCP alone (p less than 0.01). One patient in each group developed mild sedation during the treatment. It is concluded that oral lorazepam is an effective and safe adjuvant to MCP for the control of vomiting during cancer chemotherapy. PMID- 1937546 TI - Adreno cortical carcinoma in children--a case report of three cases. AB - Three cases of adrenal carcinomas are reported with emphasis on different radiological imaging techniques. It is felt that sonography and C.T. both have an important role in diagnosing masses of suprarenal region. PMID- 1937547 TI - Histiocytosis-X in Saudi children. AB - A retrospective analysis of 21 Saudi children with Histiocytosis-X were reviewed. 13 were males, 8 were females, with a ratio of 1.62:1. Five had unifocal disease while 16 were with multifocal disease. Bone involvement was seen in 19 patients (90.4%), and three patients had organ dysfunction. One patient had family history of Histiocytosis-X. Follow-up was from 1-10 years (Median 3 years). Three patients died, three had recurrences and eight patients had various disabilities (38%). Overall disease free survival was 84.2 percent. PMID- 1937548 TI - A cancer mortality study in Bombay-based atomic energy community: 1975-1987. AB - Cancer deaths recorded by the centralised health services of the Department of Atomic Energy (DAE) among its employees and their families stationed in Bombay during 1975-1987 have been analysed. Expected number of deaths due to cancer in the study group has been estimated by using the age-sex-specific cancer death rates reported for Bombay resident population for the year 1983. The size of the database for the entire DAE community is about 702,000 person years and the number of cancer deaths observed in 154. Analysis has been done separately for employees and their families, individually for important groups of cancer sites such as respiratory organs, digestive organs, breast, genito-urinary organs and lymphatic and haematopoietic systems. The standardised mortality ratios are generally lower than 100, which may partly be due to the 'healthy worker effect' in the DAE community and partly because of its differences in the social class distribution and the concomitant differences in lifestyle with respect to the comparison group of Bombay city. PMID- 1937549 TI - Non-Hodgkin's lymphoma of prostate: a rare site of primary extranodal presentation (a report of two cases). AB - We report two cases of primary extranodal lymphoma of the prostate, an unusual site for extranodal presentation. The clinical presentation and treatment is discussed. PMID- 1937550 TI - Primary lymphoma of the brain--a report of 5 cases and review of the literature. AB - Five cases of primary lymphoma of the brain are reported and the literature reviewed. The diverse clinical spectrum at presentation and variable response to therapy are few of its unique features. The literature is reviewed briefly and the importance of diagnosis at an early stage and prompt institution of therapy in form of radiation therapy and chemotherapy when indicated is stressed. PMID- 1937551 TI - Unusual splenic metastasis from oesophageal cancer. AB - The most common visceral metastasis from oesophageal carcinomas are lungs and liver. A case of splenic metastasis from a squamous carcinoma of oesophagus is reported. To our knowledge, splenic metastasis without any nodal disease has not been described previously. The pattern of reported metastasis is summarised. PMID- 1937552 TI - Effect of 9,10-dimethyl-1,2-benzanthracene on the growth of hamster dermal fibroblasts in primary culture. AB - Newborn Syrian hamster dermal fibroblasts in primary culture have high plating efficiency, manifest as homogeneous contact-sensitive monolayer in mass cultures and above all possesses a short life-span of 15-20 days in culture. These cells are quite sensitive to mutagenic carcinogens. The DMBA treatment induced multi layer and foci formation and growth in soft-agar suggesting that immortal variants can be obtained by treatment with carcinogens. PMID- 1937553 TI - Primary melanoma of the central nervous system: report of a case and review of the literature. AB - Primary melanoma of the meninges, a rare CNS tumor, is presented. Criteria for diagnosing a primary CNS melanoma are elucidated. Literature is reviewed in this context. The histogenesis of tumor, problem of occult primary melanoma and the role of CT scan and CSF cytology in early diagnosis have also been highlighted. PMID- 1937554 TI - Radical surgery for cervical carcinoma: experience with "the Tokyo method". AB - Thirty patients of cervical carcinoma were treated by radical abdominal hysterectomy and pelvic and lower paraaortic lymphadenectomy between November 1986 and October 1988 by the 'Tokyo method.' Blood loss in the majority of the patients (80%) was less than 1000 ml. The incidence of intra and postoperative complications was found to be low. None of the patients developed urinary fistula and the incidence of bladder dysfunction was also low (3.3%). Follow up of the patients for nine to 32 months revealed local recurrent tumour in only one case. We feel that the "Tokyo method" of radical hysterectomy offers several advantages over other methods. PMID- 1937555 TI - [Mycoses: new aspects and proven concepts]. PMID- 1937556 TI - [Pathogenicity of Candida albicans]. AB - Candida albicans has an advantage on other fungal opportunists, being the only fungus among the normal microbial flora on human mucosa. The potential factors of virulence of C.albicans are essentially responsible for the persistence of the yeast on mucosal surfaces. If the normal regeneration of epithelia is impeded. C.albicans may invade the mucosa. It may penetrate deeply into the host during granulocytopenia or cellular immunodeficiency, apparently using mechanisms of mimicry and the activity of secretory hydrolases. PMID- 1937557 TI - [Little known mycoses caused by dematiaceous opportunists]. AB - The mycoses caused by melanized hyphomycetes are reviewed. Agents of superficial, (sub)cutaneous, paranasal, and systemic mycoses are listed, putting the emphasis on species isolated in Germany. Adaptations to survive in extreme environments may be considered as virulence factors of these fungi. Survival inside human tissue is more or less successful depending on the immune status of the host. Several neurotropic fungi are possibly real pathogens in that they are capable of invading immunocompetent individuals. PMID- 1937558 TI - [Therapy of systemic mycoses in immunodeficiency]. AB - Fungal infections have gained importance recently. The major reason for this is the increasing number of patients with immunodeficiency. Systemic treatment of invasive fungal infections up to now has been based on relatively few antimycotic agents (amphotericin B, flucytosine, as well as the azole derivatives fluconazole and itraconazole). Only a few number of fungi cause the majority of opportunistic fungal infections. Candida albicans leads to severe mucosal infections in cases of immunodeficiency. Systemic mycoses usually present as endogenous infections or are caused by an infected central venous catheter with dissemination into multiple organs. Less severe candida infections should be treated with fluconazole. A more severe candida infection still requires treatment with amphotericin B plus flucytosine. Aspergillus fumigatus, a ubiquitous mold, is the most frequent pathogen in patients with granulocytopenia. First choice treatment also is amphotericin B and flucytosine; treatment should be started despite lacking proof of pathogen in patients with immunodeficiency and typical clinical signs. Itraconazole, the azole derivative active against aspergillus, may be administered only in mild cases of aspergillus infections in immunocompromised patients. Infections with Cryptococcus neoformans, which hardly ever occur, have been observed frequently in AIDS patients. The manifestation of cryptococcosis mainly presents as chronical meningitis. Presently various treatment concepts are being clinically tested. An initial combination of amphotericin B, flucytosine, and fluconazole, followed by long-term treatment with fluconazole, is recommended. PMID- 1937559 TI - [Interpretation of clinical and serologic findings--1 1/2 years after a long-term coccidioidomycosis]. AB - A 46-year-old soldier of the German airforce stayed in Texas/USA for 6 months. Without clinical complaints the patient revealed nodular lung infiltration and a cavern on a routine-chest-X-ray examination after his return. Serological, cytological, and histological examinations excluded a sarcoidosis, tuberculosis of the lungs and a neoplasm. The finding of precipitating antibodies and a positive skin reaction against coccidioidin led to the diagnosis of a primary pulmonary, spontaneously healed coccidioidomycosis, which did not need any antimycotic therapy. PMID- 1937560 TI - Characterization of CD44 antigen during lymphoid ontogeny. AB - We studied immunohistological and biochemical aspects of the CD44 molecule with a mAb produced in our lab: GRHL-1. The characteristic expression of this antigen in cells of B lineage was analyzed. This mAb showed identical immunohistological patterns of reactivity to other mAbs included in CD44 cluster, on a variety lymphoid and nonlymphoid human tissues, and demonstrated similar bands on SDS PAGE of 125I labeled lymphocyte lysates. This antigen is limited to cells of mature phenotype, and disappears in proliferating B cells in the germinal centers of the lymphoid follicles. CD44 is absent in pre-B and Burkitt cell lines. PKC activation mediate in vitro differentiation of pre-B cell lines. However, it is not involved in up-regulation of CD44 antigen expression. PMID- 1937561 TI - Generation of cytokines in human visceral leishmaniasis: dissociation of endogenous TNF-alpha and IL-1 beta production. AB - The role of TNF-alpha in visceral leishmaniasis is ambivalent, the eventual outcome of this infection, cure or generalization, being determined by the relative amounts of cytokines produced in vivo. Since release, by monocytes/macrophages, of TNF-alpha and interleukins 1 beta (IL-1 beta) and IL-6 is important in both the induction and effector phases of the immune responses, these mediators were determined in sera and cell culture supernatants of seventeen L. donovani infected patients in Brazil. The results are compared to those of a local control group. Circulating immunoreactive TNF-alpha in patients (median, 140 pg ml-1) was increased ten-fold over controls (median 16 pg ml-1, p less than or equal to 0.0001). In contrast, serum IL-1 beta was less than 20 pg ml-1 in all patients, although detectable in sera of 3/16 Brazilian controls (chi 2 = 3.5, p less than 0.1). Mitogen induced in vitro release of IL-1 beta and IL-6 by patients' circulating mononuclear cells was significantly reduced, and the capacity of patients' peripheral monocytes for H2O2 generation in response to opsonized zymosan was significantly diminished. In the patients, serum TNF-alpha levels were inversely related to IL-1 beta release in vitro (rho = -0.57, p less than or equal to 0.01). PMID- 1937562 TI - A review on the biological properties of C-reactive protein. PMID- 1937563 TI - 22nd meeting of the Society of Immunology. October 23-26, 1991, Lubeck Travemunde, Germany. Abstracts. PMID- 1937564 TI - Tumour necrosis factor-alpha but not interleukin-1 induces polymorphonuclear leucocyte migration through fibroblast layers by a fibroblast-dependent mechanism. AB - Interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) both induce polymorphonuclear leucocyte (PMNL) infiltration into tissues and they have a synergistic action in this respect. We and others have observed that IL-1 alpha and TNF-alpha induce 51Cr-labelled PMNL migration across monolayers of umbilical vein endothelium via an endothelial cell-dependent mechanism. Here we investigated the interaction of PMNL with fibroblasts, since PMNL probably encounter such cells in many tissues once they traverse the vascular wall. TNF alpha, but not IL-1 alpha, was found to activate fibroblast monolayers, grown on polycarbonate filters, to stimulate PMNL transfibroblast migration. This was a time- and fibroblast-dependent process which required fibroblast protein synthesis, as indicated by inhibition with cycloheximide. The effect of TNF-alpha was not related to fibroblast chemotactic factor production (primarily IL-8), or to ICAM-1 up-regulation, since IL-1 was as active as TNF-alpha in this respect, without activating fibroblasts to support PMNL transfibroblast migration. Antiserum to IL-8, present during the assay, did not inhibit PMNL migration across the monolayers. The PMNL migration was highly dependent on the function of both CD11a (LFA-1) and CD11b (MAC-1) PMNL adhesion molecules, since monoclonal antibodies to either inhibited migration by about 80%. The results suggest a distinct activation by TNF-alpha of fibroblasts to facilitate PMNL migration through fibroblast barriers. These findings may in part account for the synergistic action of IL-1 and TNF-alpha in inducing extravascular accumulation of PMNL during inflammation. PMID- 1937565 TI - Fibronectin fragments released from phorbol ester-stimulated pulmonary artery endothelial cell monolayers promote neutrophil chemotaxis. AB - We have recently shown that monolayer cultures of calf pulmonary artery endothelial (CPAE) cells pretreated with phorbol myristate acetate (PMA) generate a conditioned medium that is chemotactic for human polymorphonuclear leucocytes (PMNL). Fibronectin (Fn) is a multidomain protein found in the plasma and subendothelial extracellular matrix that induces attachment and migration of a variety of cell types. The present study was designed to evaluate the role of Fn or fragments of Fn present in conditioned medium from phorbol ester-stimulated endothelial cells as potential chemotactic factors for human PMNL. A large number of Fn fragments were revealed by Western immunoblotting of serum-free conditioned medium 4 hr after treatment of CPAE monolayers with PMA. Gelatin-Sepharose affinity chromatography of 4-hr conditioned medium demonstrated chemotactic activity for PMNL in both gelatin-binding and non-gelatin-binding fractions. The addition of bovine Fn antiserum to the conditioned medium inhibited PMNL chemotaxis in a dose-dependent manner while having no effect on PMNL chemotaxis generated by zymosan-activated serum. One site on the Fn molecule known to interact with phagocytic cells is the cell-binding domain containing the Arg-Gly Asp (RGD) sequence. Pretreatment of PMNL with a RGD-containing peptide (1 mM GRGDSPK) for 10 min completely inhibited the expression of chemotactic activity present in conditioned medium and in the gelatin-binding and non-gelatin-binding fractions. PMNL chemotaxis was not stimulated by either intact Fn or the RGD containing septapeptide tested over a wide concentration range. However, incubation of PMNL with a purified 120,000-MW fragment of Fn containing the cell binding domain stimulated chemotaxis in a dose-dependent manner. In contrast, a purified 45,000 MW fragment of Fn containing the gelatin-binding domain was not chemotactic for PMNL. When a monoclonal antibody directed against the cell binding domain of Fn was incubated with conditioned medium, a significant reduction in PMNL chemotaxis was observed. These results demonstrate that phorbol ester-stimulated pulmonary artery endothelial cells release Fn fragments and suggest an important role for Fn fragments containing the cell-binding domain in stimulating the migration of PMNL. PMID- 1937566 TI - Reciprocal haematopoietic cell transfers between C57BL/6 mice differing at the lpr locus. AB - Reciprocal transfers of spleen and bone marrow cell suspensions have been performed between mice of the C57BL/6 (B6) genetic background, differing at the lymphoproliferation (lpr) locus. These immune system chimaeras were followed for almost one year after sublethal irradiation and cell reconstitution. In addition to the survival of the chimaeras, the major lymphoid organs (bone marrow, spleen, thymus and lymph nodes) were examined for cell numbers, percentages of membrane immunoglobulin-positive cells and responses to mitogenic stimulations with concanavalin and lipopolysaccharide. The [lpr----lpr] chimaeras were similar to untreated lpr mice. The [wild----lpr] did not develop the lpr-induced syndrome and remained similar to [wild----wild] chimaeras. Therefore, B6 wild haematopoietic stem cells could rescue sublethally irradiated B6 lpr mice from the lpr-induced autoimmune pathology. The radioresistant lpr environment alone was not sufficient to induce the lpr syndrome. It may however be required for its development since [lpr----wild] chimaeras displayed a profound aplasia of their lymphoid organs, together with a normal cellularity of their bone marrow. In contrast to chimaeras constructed with MRL mice, the [lpr----wild] B6 chimaeras did not die following the lpr haematopoietic stem cell transfer. Therefore, the lymphoid aplasia of [lpr----wild] radiation chimaeras does not result from an lpr graft-versus-host-like syndrome. More likely is that a normal, non-lpr, haematopoietic environment may not allow the differentiation of the lpr haematopoietic stem cells into the lymphoid lineages. PMID- 1937567 TI - Antigen-bearing dendritic cells in the draining lymph nodes of contact sensitized mice: cluster formation with lymphocytes. AB - Following topical exposure to skin-sensitizing chemicals, Langerhans' cells, a significant proportion of which bear antigen, are induced to migrate from the epidermis to the regional lymph node. There is evidence that the antigen-bearing cells which arrive in the draining lymph nodes have the functional characteristics of mature dendritic cells (DC) and efficiently induce T lymphocyte activation in vitro and contact sensitization in vivo. In contrast, freshly isolated Langerhans' cells are known to be relatively inefficient antigen presenting cells. Evidence exists that during culture in the presence of granulocyte/macrophage colony-stimulating factor, Langerhans' cells undergo a functional maturation and assume the characteristics of dendritic cells. We have speculated that, in response to chemical exposure and the stimulus to migrate. Langerhans' cells undergo a similar maturation in vivo. To investigate this we have examined the capacity of draining lymph node DC to form antigen-independent clusters with T lymphocytes. Previous studies have confirmed that freshly isolated Langerhans' cells are unable to form such clusters. We report, however, that the antigen-bearing DC which arrive in the draining lymph nodes following skin sensitization, and which are recently derived from epidermal Langerhans' cells, efficiently form clusters with lymphocytes. Thus, antigen-bearing DC were found to have formed clusters with lymphocytes in situ in the draining lymph node, and to readily form clusters with lymphocytes in vitro. In both cases a higher proportion of lymphocytes associated with DC in clusters were T cells. An interesting observation was that DC within draining nodes appeared more efficient at cluster formation than DC in resting nodes, and that within draining nodes antigen-bearing DC formed clusters with greater affinity and/or greater stability than DC which lacked antigen. Taken together these data demonstrate that Langerhans' cell-derived antigen-bearing cells which accumulate in the draining lymph nodes following skin sensitization form clusters with lymphocytes in the manner of mature DC. This is compatible with the hypothesis that, while in transit from the skin, Langerhans' cells are subject to a functional maturation comparable to that witnessed in vitro. PMID- 1937568 TI - In situ suppression of delayed-type hypersensitivity: another mechanism for sustaining the immune privilege of the anterior chamber. AB - Immunological rejection of a highly immunogenic, syngeneic tumour (UV5C25) in the anterior chamber (AC) of BALB/c mice was analysed. Hosts developed systemic, tumour-specific cytotoxic T lymphocyte (CTL) activity (P less than 0.001) as well as systemic, tumour-specific delayed-type hypersensitivity (DTH) (P less than 0.001). Histopathological features of tumour rejection were consistent with that of a CTL-mediated process [i.e., piecemeal necrosis of individual tumour cells by tumour-infiltrating lymphocytes (TIL)]. There was no evidence of ischaemic necrosis, perivascular cuffing, infarction, or vascular damage, as expected of a DTH-mediated process. In an effort to selectively eliminate CTL or DTH effector cells and hence alter the pattern of tumour rejection, mice were treated with anti-CD8 or anti-CD4 antibodies, respectively. Elimination of either cell population not only eliminated both systemic CTL and DTH activity to this tumour, but also resulted in progressive tumour growth. Analysis of TIL from untreated tumour-bearing hosts demonstrated tumour-specific cytolysis (P less than 0.01) as well as the presence of DTH effector cells (P less than 0.01). These results indicate that while both DTH and CTL effector cells are present in the AC, only the latter are active in tumour resolution in the AC; DTH effectors are active systemically, but suppressed locally. Further, these data also suggest the requirement of a CD8+ cell population for the development of a systemic DTH response to this tumour. PMID- 1937569 TI - Phylogeny of immune recognition: role of alloantigens in antigen presentation in channel catfish immune responses. AB - Previous work from this laboratory demonstrated the importance of antigen processing and presentation in the generation of secondary in vitro immune responses of channel catfish to both simple and complex T-dependence antigens. Further, the usage of functionally active long-term monocyte lines as antigen presenting cells (APCs) revealed 'putative restriction' of immune responses by peripheral blood leucocytes (PBL) as responders. In addition, these long-term cell lines proved to be effective antigens for the production of specific alloantisera. Studies were therefore conducted to determine the importance of these alloantigens in the immunological recognition of foreign T-dependent antigens in the channel catfish. The addition of homologous, but not heterologous, alloantisera to cultures of antigen-pulsed cell line APCs and autologous immune PBL responders resulted in quantitative decreases in the antigen-specific proliferative responses. Taken together, these results provide evidence that alloantigens [presumably major histocompatibility complex (MHC) or MHC-like molecules] govern antigen presentation and putative restriction of teleost immune responses similar to the situation in mammals. PMID- 1937570 TI - Interleukin-2 receptors on rat eosinophils in adjuvant arthritis. AB - Monoclonal antibodies specific for the interleukin-2 receptor (IL-2R) have been used to demonstrate by immunohistochemical methods the presence of IL-2R on eosinophils as well as on lymphocytes in lymphoid tissue taken from rats with adjuvant arthritis. Evidence is presented which suggests that the IL-2R on eosinophils may have been induced by the disease process. PMID- 1937571 TI - Differentiation of human B-cell malignant lymphomas is independent of the octamer lymphoid specific binding factor (Oct-2). AB - We have shown previously that the presence and action of immunoglobulin gene promoter specific trans-acting factors correlates with the stages of 'differentiation' of human lymphoid neoplasms. The regulatory sequence described by us was located upstream of the octamer motif which is known to bind lymphoid specific trans-acting factor Oct-2. In the present study we attempted to establish if the Oct-2 factor was present in fresh human tissue of B-cell origin and if the levels of Oct-2 also correlated with the stages of human lymphoid differentiation. We applied DNA mobility shift assay using the same cases which we utilized in our previous work. We compared the levels of Oct-2 with the levels of ubiquitous octamer binding factor Oct-1. Oct-2 was present in all lymphoid cells of B-cell origin (from fresh surgical specimens and in long-term tissue cultured cells) with the exception of a pre-B-cell line NALM-6. The relative abundance of Oct-2 varied, however, and the ratio of Oct-2 to Oct-1 was variable in different types of B cells. This phenomenon did not correlate with the stages of differentiation of human lymphoid neoplasms. There was also no correlation between the expression of Oct-2 and levels of immunoglobulin-specific messenger RNAs. These findings indicate that the control of, immunoglobulin expression in relation to the differentiation of human B-cell neoplasms requires factors other than Oct-2. PMID- 1937572 TI - The effect of interferon-alpha on the ecto 5'-nucleotidase of human lymphoblastoid B-cell lines depends on the class of immunoglobulin secreted. AB - Thirteen immunoglobulin-secreting mycoplasma-free human cell lines were treated with increasing concentrations of lymphoblastoid interferon-alpha (IFN-alpha) in order to study the activity of their CD73 ecto-5'-nucleotidase (5'N), their rate of growth and their immunoglobulin (Ig) production. Although IFN-alpha did not immediately affect the activity of the 5'N on the cell plasma membranes, the class of Ig secreted by the cell lines determined whether culturing the cells in the presence of IFN-alpha gave a small increase in the 5'N enzyme activity (IgM), or had no effect (IgE), or showed a marked decrease in activity (IgG). The 5'N activity of two IgG4-secreting clones was more suppressed by IFN-alpha than that of the four IgG1-secreting clones. The clone with the highest 5'N was killed by IFN-alpha. A high 5'N activity inhibited the growth rate of the cells, since the rate of growth of the three IgG-producing lines with high 5'N was increased when their 5'N was inhibited by increasing concentrations of IFN-alpha. The growth rate of three other Ig-producing lines was uninhibited by up to 10(5) U/ml IFN alpha, whereas the rest were partially or strongly inhibited. Excluding the clone which died, 10/11 lines or cultures increased their Ig/cell by a mean of 25% at 100 U/ml IFN-alpha; their total Ig production also increased despite any growth inhibition. One IgG-secreting clone decreased its Ig production at 100 U/ml IFN alpha by 11%. The Ig/cell of 4/5 of the cell lines increased with IFN-alpha concentrations up to at least 10(4) U/ml. The increase in Ig/cell was not related to the class of Ig, the growth rate of the cells or the amount of 5'N. PMID- 1937573 TI - Human monoclonal antibodies with different fine specificity for digoxin derivatives: cloning of heavy and light chain variable region sequences. AB - Human-mouse hybridoma cell lines producing human monoclonal antibodies against the cardiac glycoside digoxin were established after in vitro immunization or direct immortalization of human peripheral blood lymphocytes with digoxin. Three antibodies, designated MO6, LH92 and LH1114, displayed different patterns of fine specificity against digoxin and several digoxin analogues, as elucidated by inhibition ELISA. All three monoclonal antibodies had mu heavy chains, two of them (MO6 and LH114) had kappa light chains and one (LH92) lambda light chains. DNA encoding the variable regions of both heavy and light chains of the three antibodies were amplified from cDNA using the polymerase chain reaction (PCR). The nucleotide sequences of the amplified DNA were determined after subcloning of PCR fragments in M13 vectors. The deduced amino acid sequences revealed considerable sequence differences in the complementarity determining regions between the three antibodies. PMID- 1937574 TI - IL-1 and TNF-alpha induction of IL-8 and monocyte chemotactic and activating factor (MCAF) mRNA expression in a human astrocytoma cell line. AB - In order to elucidate the role of inflammatory cytokines in the central nervous system (CNS), we examined whether IL and TNF-alpha induce cells in the CNS to produce two newly identified leucocyte chemo-attractants, IL-8 and monocyte chemotactic and activating factor (MCAF). Several human astrocytoma and glioblastoma cell lines expressed high levels of IL-8 and MCAF mRNA in vitro upon stimulation with IL-1 and TNF-alpha. In particular, an astrocytoma cell line U373MG subclone responded markedly to IL-1 with high expression levels of IL-8 and MCAF mRNA as well as IL-6 mRNA. Both IL-8 and MCAF mRNA expression depended on the dose of IL-1 and appeared as early as 30 min to 1 hr after IL-1 stimulation, confirming that these are early inducible genes. The production of IL-8 and MCAF in the U373MG cell culture supernatants was confirmed by a competitive radioimmunoassay (RIA) as well as chemotactic activities on human neutrophils and monocytes. IL-1-induced IL-8 and MCAF mRNA expression appeared to occur at least at the transcriptional level as revealed by a nuclear run-off assay. Moreover, IL-1 treatment increased the half-life of IL-8 and MCAF mRNA markedly, suggesting that increased mRNA stability was also responsible for the enhanced gene transcription. These data suggest that IL-1 and TNF-alpha induce astrocytes to produce IL-8 and MCAF transcriptionally and post-transcriptionally, both of which may be responsible for leucocytosis seen in inflammation of the CNS. PMID- 1937575 TI - A role for intestinal T lymphocytes in bronchus mucosal immunity. AB - Rats immunized by intra-Peyer's patch (IPP) injection with non-typable Haemophilus influenzae (NTHI) have been shown to clear this organism from the respiratory tract faster than non-immunized rats. We therefore performed a series of experiments in order to determine the mechanism of action of the enhanced pulmonary clearance. The experiments show that homing of intestinal T cells to the respiratory tract is an important component in the observed immunity, while specific antibody adsorbed to bacteria does not influence pulmonary bacterial clearance rate. Mucosally derived lymphocytes were collected from the thoracic duct of rats primed by IPP inoculation with NTHI, and intravenously transfused to recipient rats. These rats were shown to clear bacteria from bronchial spaces faster than non-transfused rats, or rats transfused with non-immune lymphocytes. Lymphocytes collected from the spleens of immunized rats were also capable of conferring the ability to accelerate pulmonary clearance. When thoracic duct lymphocytes (TDL) purified for T lymphocytes were transferred to recipients, the NTHI clearance rate was accelerated. In experiments to evaluate the activity of specific antibody, it was demonstrated that NTHI opsonized with antibody from bronchial washings of immunized rats was not cleared from the respiratory tract of naive rats faster than non-opsonized controls. These data indicate that immune clearance of NTHI from the respiratory tract following gut immunization is dependent upon antigen-primed lymphocytes, that primed T cells are capable of conferring this protection, and that a primary role for specific antibody in the process cannot be established. PMID- 1937577 TI - Structure of the HLA-A*0204 antigen, found in South American Indians. Spatial clustering of HLA-A2 subtype polymorphism. AB - The primary structure of the HLA-A2 subtype A*0204 (isoelectric focusing variant A2.4) has been determined. cDNA encoding this subtype was amplified by the polymerase chain reaction. Four independent full-length cDNA clones encoding A*0204 were analyzed to obtain a consensus sequence for this subtype. A*0204 differs from A*0201 by a single nucleotide change of G to T through the coding regions, resulting in an Arg to Met change at position 97. This substitution accounts for the isoelectric focusing pattern of the subtype. The same change occurs in other HLA-A specificities in association with other changes in its vicinity. The absence of additional substitutions in A*0204 suggests that it could have arisen from A*0201 by point mutation, and that recurrent mutations may take place during HLA diversification. The spatial location of this change implies that A*0204 must be a functional variant. Comparison of its sequence with other HLA-A2 subtypes reveals that much of the HLA-A2 subtype polymorphism is generated by variations in four neighboring positions, including position 97, which are located in two adjacent beta-strands on the floor of the peptide binding site of the molecule. PMID- 1937576 TI - Spontaneous alloreactivity of natural killer (NK) and lymphokine-activated killer (LAK) cells from athymic rats against normal haemic cells. NK cells stimulate syngeneic but inhibit allogeneic haemopoiesis. AB - We wanted to re-examine the hypotheses that natural killer (NK) cells preferentially react with immature cells, and that they are not directed against major histocompatibility complex (MHC) gene products. Rat marrow cells could be separated according to maturity on a four-step discontinuous density gradient of Percoll. Almost all the immature bone marrow cells with progenitor activity, as measured in vivo in a diffusion chamber assay or in vitro in a granulocyte/macrophage colony-forming assay, resided within the lighter density cell fraction (density approximately 1.065). The higher density cells (density approximately 1.082) contained mainly the more mature, non-proliferative cells within the granulocyte series. NK and lymphokine-activated killer (LAK) cells from athymic rats, being devoid of T cells, efficiently killed low- as well as high-density bone marrow cells from a fully allogeneic and a MHC congenic rat strain, while little or no killing was observed against syngeneic bone marrow cell fractions. LAK cells also effectively inhibited granulocyte/macrophage colony formation from allogeneic bone marrow precursors in vitro, while stimulating colony formation from syngeneic bone marrow cells. The NK-mediated killing of allogeneic bone marrow cells was effectively inhibited by NK-sensitive tumour cells, while there was much less inhibition of the killing of tumour cells by allogeneic bone marrow cells. We conclude that NK cells recognize MHC incompatibilities on both immature and mature allogeneic bone marrow cells through recognition systems not related to T-cell receptors, and that allospecific killing can explain the contrasting effect of NK cells on allogeneic and syngeneic haematopoiesis. PMID- 1937578 TI - Alleles at four HLA class II loci determined by oligonucleotide hybridization and their associations in five ethnic groups. AB - The use of polymerase chain reaction (PCR) and oligonucleotide hybridization offers a new approach for the definition of HLA class II alleles. It has been possible to determine 43 alleles of DRB1, four of DRB3, two of DRB4, four of DRB5, eight of DQA1, and 14 of DQB1. These alleles are inherited together in members of families and form closely associated groups which are found repeatedly and in characteristic patterns in different populations. We have determined the HLA class II alleles and analyzed their association in 431 healthy unrelated subjects including 161 North American Caucasians, 53 Latin Americans, 61 Blacks, 88 Chinese, and 68 Israeli Jews. For-locus haplotypes (DRB1; DRB3/4/5; DQA1; DQB1) were derived from 79 B cell lines and the analysis of segregation in 34 nuclear families. The B-cell lines yielded 37 and the families showed the same, and 20 other, haplotypic combinations. In addition to these 57 haplotypes, associated alleles were assigned in the unrelated panels following certain rules. The resulting haplotypes were assigned to groups known to share associated alleles. The groups were: 1) DR1, DR2, and DRw10 (13 haplotypes); 2) DR3 and DRw6 (26 haplotypes); 3) DR5 and DRw8 (24 haplotypes); 4) DR4, DR7, and DR9 (24 haplotypes). Their distribution in populations with different ethnic backgrounds was analyzed. The expressed DRB4 allele and its null mutant were determined by PCR and oligonucleotide hybridization. The different DR7 haplotypes resulting from these determinations were analyzed in a panel of 130 North American Caucasoids. This comprehensive analysis of class II HLA haplotypes in human populations should be useful in understanding the role of these genes and in various applications including anthropology, disease susceptibility, and transplantation of allogeneic organs and tissues. PMID- 1937580 TI - Concerted evolution of polymorphic MHC class II beta loci: a comment to reviewer's reply. PMID- 1937579 TI - Primate DRB6 pseudogenes: clue to the evolutionary origin of the HLA-DR2 haplotype. AB - The HLA-DR2 haplotype contains three beta-chain encoding DRB genes and one alpha chain encoding DRA gene. Of the three DRB genes, two are presumably functional (HLA-DRB1 and HLA-DRB5), whereas the third (HLA-DRBVI) is a pseudogene. A pseudogene closely related to HLA-DRBVI is present in the chimpanzee (Patr-DRB6) and in the gorilla (Gogo-DRB6). We sequenced the HLA-DRBVI and Patr-DRB6 pseudogenes (all exons and most of the introns), and compared the sequence to that of the Gogo-DRB6 gene (of which only the exon sequence is available). All three pseudogenes seem to lack exon 1 and contain other deletions responsible for shifts in the translational reading frame. At least the HLA-DRBVI pseudogene, however, seems to be transcribed nevertheless. The chimpanzee pseudogene contains two inserts in intron 2, one of which is an Alu repeat belonging to the Sb subfamily, while the other remains unidentified. These inserts are lacking in the human gene. A comparison with sequences published by other investigators revealed the presence of the HLA-DRBVI pseudogene also in the DR1 and DRw10 haplotypes. Measurements of genetic distances indicate DRB6 to be closely related to the DRB2 pseudogene and to the HLA-DRB4 functional gene. In humans, gorillas, and chimpanzees, the DRB6 pseudogene is associated with the same functional gene (DRB5) indicating that this linkage disequilibrium is at least six million years old and that DR2 is one of the oldest DR haplotypes in higher primates. PMID- 1937581 TI - The effects of polyamines on the immunogenicity of polynucleotides. AB - Polyamines--putrescine, spermidine, and spermine--are small organic cations that are present in all living cells. Recent studies revealed that polyamines could provoke a left-handed Z-DNA conformation in poly(dA-dC).poly(dG-dT) and related alternating purine-pyrimidine sequences. In order to examine whether polyamine induced Z-DNA conformation of poly(dA-dC).poly(dG-dT) is capable of eliciting anti-Z-DNA antibodies, we immunized rabbits with poly(dA-dC).poly(dG-dT) in the presence and absence of spermidine and spermine. Rabbits immunized with the polynucleotide alone produced antibodies reacting toward poly(dA-dC).poly(dG-dT) and heat-denatured calf thymus DNA (ssDNA). In contrast, immunization with poly(dA-dC).poly(dG-dT) complexed with spermidine or spermine produced antibodies reacting with Z-DNA in addition to those binding toward poly(dA-dC).poly(dG-dT) and ssDNA. Antibodies elicited by polynucleotide.polyamine complexes had no reactivity toward polyamines. Solution inhibition studies suggested that anti poly(dA-dC).poly(dG-dT), anti-ssDNA and anti-Z-DNA antibodies are distinct populations that favor each one of these antigens. Our results suggest that natural polyamines are capable of altering the immunogenicity of polynucleotides by mechanisms involving the stabilization of Z-DNA conformation. This result may have implications in the recent findings of high levels of polyamines and anti-Z DNA antibodies in the sera of lupus patients and autoimmune mice. PMID- 1937582 TI - The generation of antibody in mice to tuftsin: a naturally occurring phagocytosis stimulating tetrapeptide. AB - Tuftsin (Thr-Lys-Pro-Arg) is a naturally occurring tetrapeptide that stimulates most known functions of the polymorphonuclear leukocyte and macrophage cell lines. We previously reported our unsuccessful attempts to generate antituftsin antibodies by conjugating tuftsin to several carrier proteins and by polymerizing the peptide with glutaraldehyde. To render tuftsin antigenic the following modifications were made to native tuftsin: three glycine residues were added to the N terminus of tuftsin (Gly3-tuf) and cysteine was added to the N terminus (Cys-tuf) and to the C terminus (tuf-Cys). Native tuftsin was covalently conjugated to sheep red blood cells (SRBC). In a separate experiment Balb/c mice primed with SRBC were immunized with 10(7) SRBC peptide conjugate. Native tuftsin and Gly3-tuf were also conjugated to keyhole limpet hemocyanin (KLH). In another experiment KLH and cationized bovine serum albumin (cBSA) were activated with sulfo-succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (s-SMCC), which was used to control orientation of tuf-Cys and Cys-tuf when conjugated to each carrier protein. All conjugates were administered in complete Freund's adjuvant (CFA) except for cBSA conjugates which were administered in alum. Antibody response was determined by solid phase radioimmunoassay. Results showed that specific antituftsin antibodies were elicited only by Cys-tuf, conjugated to KLH. This study reaffirms that tuftsin is weakly antigenic and confirms the previous work by Gottlieb et al. that antibody to tuftsin can only be elicited when tuftsin is conjugated to the carrier protein KLH in a manner that leaves the peptide carboxyl end free. PMID- 1937583 TI - Enhancement by restraint stress of natural killer cell activity and splenocyte responsiveness to concanavalin A in Fischer 344 rats. AB - Stress usually has a depressing effect on immune function. However, we observed apparent immune enhancement following restraint stress. Fischer 344 rats were restrained in snug--fitting wire mesh tubes for 14 hr/day during the light portion of a daily 14:10 hr light/dark cycle for 0, 11, 22, or 33 days. Animals were sacrificed immediately after the last restraint session, and trunk blood and spleens were collected. Blood neutrophil percent was significantly higher after 11 or 22 days of restraint than in controls, as expected, and returned to baseline at 33 days. However, natural killer activity of spleen cells against Yac 1 targets, measured by a lactate dehydrogenase (LDH) release assay, was higher than controls after all periods of restraint, and especially after 11 days. Responses to concanavalin A by spleen cells from restrained rats were also higher than controls after all periods of restraint. PMID- 1937584 TI - Binding of endotoxin to macrophages: distinct effects of serum constituents. AB - The respective roles of serum lipoproteins, and of the complement component C3, in the binding of endotoxin (LPS) to macrophages were analyzed by an in vitro assay using [3H]LPS. The addition of an anti-C3 serum in the medium induced an apparent abolishment of the specific binding of LPS to mouse macrophages, but this effect appeared to be due to an actual increase of nonspecific binding. Isolated complexes of LPS with lipoproteins of high density (HDL3) and of very high density (VHDL) did not bind to macrophages. Furthermore, addition of HDL3 and VHDL in the incubation medium inhibited the specific binding of LPS to macrophages. These results suggest that C3 reduces nonspecific interactions between LPS and macrophages whereas associations between LPS and HDL3 or VHDL inhibit specific LPS-macrophage interactions. PMID- 1937585 TI - Chemotactic cytokine (IL-8 and MCP-1) gene expression by human whole blood. AB - The salient features of systemic or local inflammation are the myriad of cellular and humoral interactions that result in elicitation of inflammatory leukocytes. In this study using specialized connective tissue, intact whole blood, we demonstrate the gene expression of two novel chemotactic factors. The buffy-coat cellular expression of neutrophil chemotactic/activating factor/interleukin 8 (IL 8) and monocyte chemotactic/activating protein (MCP-1) mRNA were time and dose dependent in response to either lipopolysaccharide or zymosan stimulation. This system with the complexity of tissue provides a unique model for the determination of chemotactic cytokine gene expression. PMID- 1937586 TI - Interleukin 2 induces tumor necrosis factor gene expression in vivo. AB - Interleukin 2 (IL-2) treatment of malignancies is often associated with severe toxicity, and the alterations observed after high dose administration of IL-2 are similar to those induced by recombinant tumor necrosis factor (TNF). We therefore examined the hypothesis that IL-2 induces TNF gene expression in vivo. Purified, recombinant human IL-2 was injected intraperitoneally into mice which had been previously primed with complete Freund's adjuvant (CFA). Biologically-active TNF was detected in the ascites fluid of CD-1 mice; it was detectable 30 minutes after IL-2 and peaked at 1 hour (500 +/- 158 units/ml). Plasma levels of TNF also peaked at 1 hour at 32 +/- 4 units/ml. Similar kinetics were observed in CBA/J mice. TNF specific mRNA was also present in the ascites cells, and peaked 30 minutes after IL-2 injection into CBA/J mice. Injection of vehicle containing 10 times the maximum contaminating dose of endotoxin did not induce TNF above background levels. As a further control for potential endotoxin contamination, IL 2 was injected into endotoxin hyporesponsive C3H/HeJ mice. These mice also demonstrated the rapid upregulation of biologically-active TNF in the ascites, with peak production occurring at 1 hour (125 +/- 47 units/ml). The induction of biologically-active TNF in the C3H/HeJ mice was associated with a peripheral blood neutrophilia and lymphopenia, pathophysiologic alterations that have been attributed to TNF. These data show that a single injection of purified, recombinant IL-2 induces TNF gene expression in vivo. PMID- 1937587 TI - Rat basophilic leukemia cells: protein kinase C and secretion. AB - Phorbol myristate acetate (PMA) but not its inactive analogue phorbol didecanoate modulated the release of [3H] serotonin by rat basophilic leukemia (RBL) cells stimulated by antigen-IgE complexes. Concanavalin A or the calcium ionophore ionomycin, suggesting that protein kinase C (PKC) was involved in the exocytosis process. The PKC inhibitor sphingosine markedly inhibited release. When the PKC content of RBL cells was diminished by a prior 24 h-exposure (long-term PMA treated cells) to 50 or 100 ng/ml PMA, the release induced by the three secretagogues was also strongly inhibited. Since cell activation by PMA in different cell systems is accompanied by PKC translocation from cytosol to membrane, we studied the location of PKC in resting cells and its translocation by a 5 min-exposure to 100 ng/ml PMA. PKC was cytosolic in long-term PMA-treated and control RBL cells and its translocation occurred regardless of the total PKC cell content, showing a possible correlation between the level of functional PKC (susceptible to be translocated) and exocytosis. Taken together, these data suggest that PKC is involved in the controlling of exocytosis by different secretagogues. PMID- 1937588 TI - Characterization of temperature sensitive mutants of Japanese encephalitis virus isolated from persistently infected mammalian cells. AB - Four new temperature-sensitive (ts) mutants of Japanese encephalitis virus (JEV) isolated from porcine kidney cells persistently infected with JEV and seven previously isolated ts mutants were studied. Of the eight mutants tested, five mutants ts1, ts14, ts36, ts48 and ts71, were thermolabile. Analyses of virus induced intracellular polypeptides revealed that with majority of the ts mutants, when grown at restrictive temperature, the viral proteins were quantitatively affected. All the five ts mutants tested for mouse virulence showed attenuation in infant mice by the intracerebral route. Two ts mutants, ts36 and ts48, escaped neutralization with two anti-JEV envelope protein specific monoclonal antibodies, however, these escape mutants reacted efficiently with the same monoclonal antibodies in antigen capture ELISA. PMID- 1937589 TI - Characterization of & induction of immune response to anti-idiotypic antibodies for JE virus. AB - Anti-idiotypic antibodies (anti-Ids, Ab2s) were prepared by immunizing rabbits with two murine monoclonal antibodies (Ab1) having specificities for two independent haemagglutinin (HA) epitopes on JE virus [viz., Hs-1, monoclonal antibody (MAb) specific for Japanese encephalitis virus (JEV) and Hx-1, MAb common to flaviviruses]. Anti-Hs-1 (S-Ab2) and Anti-Hx-1 (X-Ab2) reacted specifically with the immunizing Ab1. In addition, they could react with other MAbs whose reactivity was similar to their immunizing homologous Ab1. The paratope inhibition assay indicated that both anti-idiotypes recognized paratope related idiotopes on their respective Ab1 and could therefore be designated as Ab2 beta. Experimental animals (Swiss mice, Balb/c mice and guineapigs) immunized with S-Ab2 or X-Ab2 produced anti-JE virus antibodies (Ab3) which could be detected by enzyme linked immunosorbent assay, immunofluorescence, haemagglutination inhibition and neutralization tests. The anti-idiotypes were also found to stimulate a cellular immune response in vitro as assessed by 3H thymidine incorporation by lymphocytes from JE vaccinated individuals and experimentally immunized Balb/c mice. The findings of the present study suggest that both the anti-Id antibodies are homobodies which may act as surrogate antigens to manipulate the immune response against JEV. PMID- 1937590 TI - Hepatitis B infection among dental personnel in Pune & Bombay (India). AB - To assess the risk of hepatitis B infection among dental personnel, serum samples were collected from dentists of Pune and students, staff, auxiliary staff and class D staff of a dental college in Bombay. Dentists (32.02%), dental auxiliary staff (35.89%), clinical assistants and post-graduate students (19.56%) were found to have significantly higher prevalence of HBV infection as compared to undergraduate dental students (3.94%). The prevalence of HBV infection was high among the dentists as compared to voluntary donors. A positive linear association was observed in the positivity of HBV seromarkers with increasing age and number of years spent by the workers in the dental environment. The rate of increase in HBV seropositivity with age was higher (P less than 0.05) among dental personnel when compared to voluntary donors. Vaccination against hepatitis B is recommended for all the dental students before they start their clinical phase and for susceptible dentists and dental auxillary staff. PMID- 1937591 TI - Development of Leishmania donovani in Phlebotomus argentipes & Ph. papatasi fed on kala-azar patients in Bihar. AB - A total of 258 laboratory bred Ph. argentipes was fed on untreated parasitologically confirmed kala-azar patients. Successful development of parasites was noted in 0.54 per cent Ph. argentipes fed during the day and 5.33 per cent fed during the night. However, none of the 245 laboratory bred Ph. papatasi fed on the same patients, was found positive for successful development of L. donovani in the foregut. PMID- 1937592 TI - Epidemiology of kala-azar in rural Bihar (India) using village as a component unit of study. AB - It is assumed that some features like intra-macrophage habitat of the Leishmania parasites, rare availability of infected macrophages in peripheral blood for vector sandflies to suck in, short flight range of sandflies, non-availability of an animal reservoir encountered in visceral leishmaniasis indicate slow and limited transmission potential and even so epidemics occur every 15 to 20 yr. To verify if these assumptions are true, the natural history of kala-azar was studied, using an endemic village in Bihar (India) as an unit of study, over a period of 5 yr (1984-1988). Village Jethuli is bound by the river Ganga on the north and separated from neighbouring endemic villages on other three sides by agricultural land, is isolated entomologically (as regards sandflies). The village has a population of 3236 persons of different social status and depending on economic conditions have three types of dwellings, brick made with cement plaster, brick made with mud plaster and mud houses. The first case of kala-azar was reported in a migrant from district Vaishali on the other side of Ganga where kala-azar appeared in an epidemic form. Studies showed that the infection is built up slowly, first in the same house and then in the immediate neighbourhood. In this village, maximum number of cases occurred in 1984 and 1985, and they were treated by our Institute and cured. In subsequent years, only a few cases occurred (i.e., 6 in 1986 and 4 in 1987) while no case occurred in 1988.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937593 TI - Dot immunobinding assay versus sandwich ELISA in diagnosis of invasive amoebiasis. AB - Sera from 34 patients of amoebic liver abscess (ALA) and 11 patients with amoebic dysentery (AD) were examined for the presence of specific Entamoeba histolytica (EH) antibodies and amoebic antigen by enzyme linked immunosorbent assay (ELISA) and dot immunobinding assay (DIB). Both techniques were found to be equally sensitive for detecting antiamoebic antibodies (89.5 and 91.9% respectively) and highly specific (100%) in patients of ALA. ELISA was found to be more sensitive (94.4%) in detecting circulating amoebic antigen compared to DIB (68%) in patients of ALA. Specific antibodies, in significant levels, were detected in 3 and 5 patients of AD by ELISA and DIB assay, respectively. As DIB assay is easier to perform and less expensive, is recommended for detection of antibodies in patients with invasive amoebiasis. PMID- 1937594 TI - Enterotoxin production & mouse virulence of clinical isolates of Salmonella typhimurium strains. AB - Twenty five isolates of S. typhimurium from clinical specimens were studied for markers of virulence. Three of five isolates from blood, both isolates from CSF and urine and only two of fifteen isolates from faeces were positive for fluid accumulation in rabbit ileal loop. All these strains produced an enterotoxic principle, antigenically related to cholera coli family of enterotoxins, as detected by latex agglutination and immuno-dot-blot tests. Polymyxin-B treated 6 h cultures yielded the best toxin. All 5 blood isolates, both CSF isolates and one of the two urine isolates showed low LD50 indicating high virulence. The study thus revealed that some strains of S. typhimurium are more virulent and produce more enterotoxins. These strains invade the intestinal mucosa potently and lead to extra-intestinal manifestations. The low virulent strains, on the other hand, are confined to the intestine and cause mild/moderate gastroenteritis. Enzyme assays were done in 5 representative strains of good, moderate and low toxin producers. Catalase and superoxide dismutase assays did not show any correlation with toxin production, thus suggesting that the enzyme production is unlikely to be a reliable indicator of the virulence for S. typhimurium. PMID- 1937595 TI - Detection of Bacteroides infection by counter immunoelectrophoresis test. AB - The counterimmunoelectrophoresis (CIE) test using sonicated antigens of Bacteroides fragilis NCTC 2553 and a B. asaccharolyticus strain, standardised in the laboratory yielded a negative result in the 50 normal sera tested, while it was positive in 24 of 34 (71%) patients with infection due to black pigmented bacteroides and in 10 of 15 (67%) with B. fragilis infection. The microagglutination test (MAT) done in parallel showed a positivity of only 44 and 40 per cent respectively. The CIE test done with B. asaccharolyticus antigen was negative in 87 per cent of patients with infection due to B. fragilis whereas MAT showed cross reactivity to a greater extent. PMID- 1937596 TI - Entomological investigations during outbreaks of dengue fever in certain villages in Maharashtra state. AB - Outbreaks of dengue (DEN) fever are reported from 22 villages in five districts in the state of Maharashtra. DEN viral antigen was detected by indirect immunofluorescence test in 34 of 375 female Aedes aegypti mosquitoes collected from 8 villages. DEN types 2 and 3 were identified among the 16 strains that were isolated. None of the 64 male mosquitoes showed the presence of viral antigen; 281 males and 323 females reared from field collected larvae were also found negative. Indoor spraying of DDT in the affected villages produced a drastic reduction in Ae. aegypti catches. No viral antigen was detected in mosquitoes caught subsequent to the spray. With the introduction of water supply through taps, which is often inadequate, people are compelled to store water for domestic purposes, which favours an increase in Ae. aegypti breeding. In view of changing rural ecology associated with the development process, continued surveillance of the spread of Ae. aegypti as well as the diseases borne by this vector are recommended. PMID- 1937597 TI - Susceptibility studies on Culex tritaeniorhynchus Giles, 1901, to insecticides in the state of Goa. AB - Tests conducted on the adults of C. tritaeniorhynchus in Goa during 1988-89 against organochlorine, organophosphate and carbamate insecticides showed that the LC50 values against DDT and dieldrin after 1 h of exposure were 2.2 and 1.2 per cent respectively. The LT50 values against malathion (5%), fenitrothion (1%) and propoxur (0.1%) were 19, 22 and 35 min respectively. Thus, taking into consideration the base-line data available for C. quinquefasciatus, the species can be considered susceptible to dieldrin, malathion, fenitrothion and propoxur. However, the results with DDT were equivocal and require verification. PMID- 1937598 TI - In vivo experimental model to evaluate the insect repellent N-N, diethylphenylacetamide in Periplaneta americana Linn. AB - The responsiveness of insect antennae to bornyl acetate (BA), a sex pheromone mimic and N,N-diethyl phenylacetamide (DEPA), a multi-insect repellent has been studied. Electrical activity from the antennal lobe was quantified to observe the alterations in power and frequency spectrum in P. americana Linn. following exposure to these chemicals. Two distinct patterns of responses were exhibited on exposure to BA and DEPA, the former producing a marked excitation and the latter inhibition of electrical discharge during the exposure to these compounds at a concentration of 200 micrograms. PMID- 1937599 TI - Multicentric randomized controlled clinical trial of Kshaarasootra (Ayurvedic medicated thread) in the management of fistula-in-ano. Indian Council of Medical Research. AB - This paper reports the results of a multicentric, randomized controlled trial to evaluate the efficacy of Kshaarasootra (Ayurvedic medicated thread) in the management of fistula-in-ano, in comparison with conventional surgery. This trial was carried out at Bombay, Chandigarh, New Delhi and Wardha. Complete healing was noted in all 265 patients in the Kshaarasootra series and all 237 patients in the surgery series. The median healing time was, however, significantly longer in the Kshaarasootra series (8 wk) than in the surgery series (4 wk). In both the series, the healing time was least for subcutaneous fistula and highest in the case of high anal fistula. Patients in both the series are being followed up for one year after the completion of treatment, and the recurrence rates, based on 150 patients in each series are 4 per cent in the Kshaarasootra series and 11 per cent in the surgery series, a significant difference (P = 0.03). Transient local burning and increased discharge from the fistulous opening were observed in most patients treated with Kshaarasootra. Mild anal incontinence was observed in 8 patients treated with Kshaarasootra and 13 patients treated with surgery. It is concluded that the long-term outcome with Kshaarasootra is better than with surgery, although the initial healing time is longer. Kshaarasootra thus offers an effective, ambulatory and safe alternative treatment for patients with fistula in-ano. It also constitutes a new drug delivery technique for conditions like anal fistula. PMID- 1937600 TI - A four year study on neonatal morbidity in a New Delhi hospital. AB - The neonatal morbidity was studied in 7015 neonates born at the All India Institute of Medical Sciences Hospital, New Delhi. The incidence of low birth weight babies was 26.7 per cent; one seventh (13.5%) of the series were preterm (less than 37 wk), while 6.6 per cent were 'small-for-dates'. Birth asphyxia of varying severity developed in 5.9 per cent infants. Respiratory distress syndrome was diagnosed in 5.7 per 100 live-births; most being due to hyaline membrane disease (33.5%), which affected 14.1 per cent of preterm babies. Neonatal hyperbilirubinemia occurred in 5.9 per cent, most of whom were premature. In nearly one-fifth, the cause of jaundice could not be identified after detailed investigations. Minor bacterial infections (conjunctivitis, pyoderma, oral thrush, umbilical sepsis) were observed in 1.8 per cent while major infections (septicemia, meningitis, diarrhoea) in 3.0 per cent. The overall incidence of major malformations was 2.3 per cent. Reasons for low incidence of bacterial infections and common occurrence of hyaline membrane disease in premature infants, are highlighted. PMID- 1937601 TI - Serum cholesterol levels in carcinoma breast. AB - A total of 56 histologically confirmed cases of carcinoma breast were analysed in terms of serum cholesterol levels, age, religion and dietary status of the patients. Age-matched controls from the same geographical area were chosen from the relatives/attendants of patients, to rule out the possible influence of environment, socio-economic, cultural and dietary practices. The mean serum cholesterol level of patients was 193.07 mg/dl (+/- 36.39), as compared to 216.32 mg/dl (+/- 30.51) in the controls (P less than 0.001). A significant difference in the blood cholesterol levels between non-vegetarian and vegetarian patients was also observed (P less than 0.001), as also between vegetarian and non vegetarian patients and the controls (P greater than 0.025). PMID- 1937602 TI - Diagnostic accuracy of immediate interpretation of fine needle aspirates. AB - A total of 197 fine needle aspirates (FNA) from various body sites was subjected to immediate interpretation to determine its diagnostic accuracy. For the entire series, the immediate interpretation revealed a sensitivity of 97 per cent, specificity of 96 per cent, a positive predictive value (PV) of 92 per cent, a negative predictive value of 98 per cent and an efficiency of the test of 96 per cent. The false positive rate was 1.5 per cent and false negative rate 0.5 per cent. The diagnostic accuracy of immediate interpretation was comparable for aspirates from different sites. Our results indicate that immediate interpretation of FNA is ideal for determining the adequacy of material and providing a rapid basic diagnosis. This technique could offer useful substitute to frozen sections particularly when facilities for the latter are not available. PMID- 1937603 TI - Light & electron microscopy of proliferating oval cells during early chemical hepatocarcinogenesis. AB - Early hepatic changes were studied in male albino rats (70) of Sprague Dawley strain fed a choline devoid diet containing 0.05 per cent w/w AAF (2 acetylaminofluorene) for 12 days. Proliferating periductal and ductal cells appeared in the portal area on days 1 and 3 respectively in the experimental group. On day 7, these cells infiltrated within the sinusoids of adjacent lobules up to the first one or two layers of hepatocytes. Subsequently, these cells extended up to the midzonal region on day 21 and by day 24 the entire lobule was infiltrated. Formation of duct like structures by the proliferating cells was seen on day 21. Ultrastructurally both periductal and ductal cells showed only a few organelles. Periductal and ductal cells are the earliest cells to appear in the portal area in chemically induced hepatocarcinogenesis. Its undifferentiated ultrastructure, may suggest the stem cell nature of these cells. PMID- 1937604 TI - Serum potassium levels following suxamethonium administration in septic peritonitis patients. AB - Serum potassium and sodium changes following suxamethonium (1.5 mg/kg) administration were studied in 25 patients with septic peritonitis and 25 with no signs of peritonitis. A highly significant rise (P less than 0.001) in serum potassium (0.1-2.5 mEq/l) above the pre-induction levels was observed following suxamethonium administration in patients with septic peritonitis with maximum rise at 5 min following suxamethonium. This rise in potassium was significantly higher (P less than 0.001) in peritonitis patients at 3,5, and 10 min interval. A positive correlation was found between rise of potassium and duration of illness (P less than 0.01). No statistically significant changes were observed in serum sodium levels in both groups. PMID- 1937605 TI - Vascular morphology in testes of infertile males with varicocele. AB - Testicular biopsies of 38 infertile males with varicocele were examined for vascular changes. Endothelial prominence, intimal fibrosis and increased amount of collagen in the media were present in veins, venules and capillaries. The small vessels were thickened with the deposition of homogeneous bluish pink material. The material stained green on Van Geison stain. The vascular changes were bilateral even in patients of unilateral varicocele. The severity of these changes was not related to tubular morphology. PMID- 1937607 TI - High versus low approach for internal jugular cannulation with double lumen catheters. AB - Double lumen cannulae were inserted through the right internal jugular vein (IJV) in 100 children, undergoing open heart surgery. High approach (n = 50, group I) of IJV cannulation was compared with low approach (n = 50, group II). In both the groups, hydromer coated double lumen polyurethane cannulae (Hydrocath) were introduced using Seldinger's technique; 98 per cent success rate was achieved in both the groups. Tip of cannulae was in intrathoracic position in 100 per cent patients. One patient in group I had carotid artery puncture. Catheter blockage occurred in one patient each in both the groups. Double lumen catheters are easy to insert and offer two lumens through single puncture site. PMID- 1937606 TI - Incidence & outcome of aluminium phosphide poisoning in a hospital study. AB - A total of 418 patients with aluminium phosphide poisoning admitted during January 1981 to December 1987, were studied and analysed for various clinical parameters. A steady increase in the number of patients was seen during the last 7 yr. Maximum number belonged to the younger generation and nature of poisoning was suicidal in most of these patients. Dose of poison consumed varied, but most patients consumed two tablets (6 g). A wide range of symptoms and signs was seen, the commonest being gastrointestinal manifestations and shock. Cardiac arrhythmias and conduction disturbances were seen in 38.2 per cent patients. The overall mortality was 77.2 per cent. Indices of a bad prognosis included poor response to dopamine infusion and continuous increase in its dosage, chest infections, adult respiratory distress syndrome and disseminated intravascular coagulation. The complications noticed were pericarditis, congestive cardiac failure, acute gastrointestinal haemorrhage and acute respiratory arrest. Histopathology of various organs showed changes suggestive of cellular hypoxia but the mechanism of ECG changes and of the complications could not be elucidated. PMID- 1937608 TI - Comparative study on proper placement of central venous catheters with & without stillete. AB - Observing a standard protocol, central venous catheterization was performed, via the right basilic vein, in 100 patients. At random, 50 patients received a catheter with stillete and 50 without stillete. Catheter tip was localized on a chest radiograph; 78 per cent with stilletes and 80 per cent without stilletes were properly positioned (either in the right atrium or the superior vena cava). Most common aberrant placement was in the right ventricle (14% of each type of catheters), and this did not produce any ventricular arrhythmias. Eight per cent of catheters with stillete and 6 per cent without stilletes were malplaced into the ipsilateral internal jugular vein. The incidence of proper and improper placement was similar with the two types of catheters. Silent catheter migration into the right ventricle is very frequent than recognized when an estimated catheter length is inserted without radiologic control. PMID- 1937609 TI - Central hyperthermic effect of arsenic in rabbits. AB - Hyperthermic effect of arsenic was investigated in rabbits. Injections of arsenic trioxide (0.0001 to 0.1 micrograms) into a lateral cerebral ventricle of the rabbit evoked a dose-dependent hyperthermia, respiratory stimulation and peripheral vasodilatation. Heat loss through respiratory stimulation and peripheral vasodilatation appeared responsible for the long latent period and the slight hypothermia sometimes obtained during this period as these effects followed the same time course. These effects were centrally mediated as demonstrated by the lack of efficacy of the same doses by the intravenous route. The hyperthermic effect of arsenic was antagonized by the sulphydryl donator, dimercaprol, the a-adrenoceptor blocking agent-phenoxybenzamine and the PG synthesis inhibitor-aspirin. Multiple sites, for antagonistic effects of these substances can be explained by the action of arsenic in inactivating sulphydryl containing enzymes which are many and catalyze diverse biochemical reactions. PMID- 1937610 TI - Role of allogenic vesical mucosa in inducing neo-osteogenesis in guineapigs. AB - Fresh allogenic mucosa lining the urinary bladder was transplanted into a 1 cm gap of right ulna bone in 24 guineapigs. The 1 cm, bone gap in the left ulna served as control. At regular intervals, the implanted and control sites were studied grossly with naked eye, radiologically and histopathologically to ascertain the role of allogenic vesical mucosa in inducing neo-osteogenesis. The bone gaps were uniformly bridged by bone in 10-12 wk at the implanted sites and fibrous tissue at control sites. There was no evidence of graft rejection. The study thus suggests the potential of the use of stored allogenic vesical mucosal grafts for neo-osteogenesis in clinical practice. PMID- 1937611 TI - Immune status in ataxia telangiectasia. AB - Immune status of 22 patients of ataxia telangiectasia was studied over a period of 8 yr (mean age of patients: 9.5 +/- 3 yr; 9 of 22 were siblings). Low T-cell number was observed in 14 of 19 patients but the response to PHA challenge done in 10 patients was normal and migration inhibition to BCG antigen was positive in 6 of 6 patients. IgM defect was seen in 2 out of 18 patients and serum IgA was deficient in 10 out of 18 patients. Salivary IgA was also absent in these children. Four children had high spontaneous NBT reduction. None of the patients had lymphoma, leukemia or any other malignancy at the time of presentation. Candida killing was normal in all patients. The presenting feature related to the CNS in almost all children and gross infections were not seen. PMID- 1937612 TI - HLA-DRB nucleotide sequences arranged in polymorphic groups. AB - The nucleotide sequence information of HLA-DR B genes is presented in this short review in a format which is useful for designing sequence specific oligonucleotides (SSOs) for DNA typing. The relationships between various HLA-DR alleles are also shown. PMID- 1937613 TI - Child survival and child health development activities for the eight five year plan in India (1990-1995)--I. Planning Commission, Government of India. PMID- 1937614 TI - Menarcheal age and growth pattern of Indian girls adopted in Sweden. II. Catch-up growth and final height. AB - Adopted girls (n = 107) previously studied regarding menarcheal age in relation to age at arrival, were analysed as to growth pattern and final height related to nutritional status at arrival and menarcheal age. It was found that most girls had catch-up growth regarding height and half of them regarding weight. Faster catch-up and later arrival age in Sweden were associated with earlier menarche. The catch-up growth was, however, incomplete, and lower the initial height for age, lower was the height for age at the succeeding measurements, and the final height. The mean final height was 154 cm, but 8% of the girls were 145 cm or shorter. The data suggest that linear growth and final height is influenced by the preadoptive nutritional condition, as well as by the degree and timing of subsequent catch-up growth, and the timing of puberty. Pubertal onset is related to the degree and timing of catch-up growth. PMID- 1937615 TI - Transient adrenal suppression during early dexamethasone therapy. PMID- 1937616 TI - Neonatal tetanus: observations on antenatal immunization, natal and immediate post-natal factors. AB - The objective is to study the present status of the antenatal immunization with tetanus toxoid and the natal and immediate postnatal factors among the cases of neonatal tetanus and the changes over time. Retrospective analysis of 61 case records of Neonatal Tetanus (NNT) during 1987-88 and prospective study of 19 cases of 1989 was done. The number of cases have decreased considerably from 88 in 1984 to 19 in 1989. 80% of cases were from residents outside the city. Antenatal checkup improved from 37.7% in 1987 to 73.7% in 1989. The proportion of mothers of NNT cases who received = greater than 2 doses have increased from 19.7% in 1987-88 to 31.6% in 1989. In the year 1989, 21% and 10.5% have received the I and II doses of TT respectively at the 9th month of pregnancy, the value of which is doubtful. Majority (73.7%) were domiciliary deliveries conducted by dhais and this has not changed over the years. The importance of antenatal booking, immunization at the appropriate time, hygienic obstetric and cord care are stressed. PMID- 1937617 TI - Effectiveness of ARI control strategy on underfive mortality. AB - A prospective intervention study was conducted in Ballabgarh block of Haryana. The study area has a population of about 30,000 under a state run P.H.C. area. The control area has a population of about 60,000 under Comprehensive Rural Health Services Project of All India Institute of Medical Sciences. ARI control strategies as advocated by WHO was instituted in the study area. Measles and DPT immunization was strengthened. The ARI cases detected or reported to Health Workers were managed as per the standard case management procedure. The underfives mortality, infant and 1-4 years mortality rates were initially higher in study area and differences were statistically significant. After 2 years, the reductions in study area were substantial and differences were not statistically significant. The ARI mortality in underfives, and 1-4 years were higher in study area at the beginning compared to control area. Though they were less than in control area after 2 years of intervention the observed differences were not statistically significant in both periods. The reduction of 37% in underfives mortality and 26% due ARI mortality is substantial. More benefit was attained with measles immunization than with standard case management. ARI control programme is advocated for application on national level vigourously covering with measles immunization and to include the village based private practitioners in the strategy for effective case management. PMID- 1937618 TI - Strategy for improved nutrition of children and women in developing countries. United Nations Children's Fund. PMID- 1937619 TI - Isoniazid or rifampicin versus bacillus Calmette-Guerin (BCG). PMID- 1937620 TI - Pediatric emergency news letter no. 13. PMID- 1937621 TI - The Sjogren-Larsson syndrome in a north Indian sibship. PMID- 1937622 TI - The late presenting congenital diaphragmatic hernia simulating hydropneumothorax. PMID- 1937623 TI - Prenatal diagnosis of duodenal atresia by ultrasound. PMID- 1937624 TI - Neonatal cholera in a hospital born baby. PMID- 1937625 TI - Festschrift to honor Professor O.P. Ghai. PMID- 1937626 TI - Growth of pediatrics in India: the need for development. PMID- 1937627 TI - Role of insulin in the fetus. PMID- 1937628 TI - Glucose metabolism in the mother and the newborn infant. PMID- 1937630 TI - Guidelines for research. Indian Council of Medical Research, New Delhi. PMID- 1937629 TI - Neonatal hypoglycemia following maternal glucose infusion prior to delivery. AB - Intravenous glucose therapy to mother prior to delivery significantly affects glucose and insulin homeostasis in fetus and newborn infants. Specifically, the infants show hyperglycemia, and hyperinsulinism at birth, and are predisposed to hypoglycemia in the first few hours of life. In this paper we have focussed attention on the clinical significance of these changes and suggest some remedial measures, in light of our own research. PMID- 1937631 TI - Monitoring of perinatal asphyxia in the hospital. PMID- 1937632 TI - Foetal co-relates and mode of delivery in asphyxia neonatorum. AB - A prospective study was conducted on consequitively born live births for determining the role of certain foetal factors and mode of delivery on asphyxia neonatorum. The difference in the incidence of neonatal asphxia in 1208 singleton births (8.5%) and in the 66 multiple births (9.7%) was statistically significantly (p less than 0.01). Among the singleton live births a significantly increased incidence of asphyxia was recorded in preterms when compared to term and post term babies collectively (p less than 0.001). Small for date babies were at a greater risk for asphxia neonatorum when compared to babies weighing appropriate for gestational age (p less than 0.001). An inverse relationship was observed between birth weight and asphyxia neonatorum. A significant difference was seen in the occurrence of neonatal asphyxia between babies weighing less than 2000 g. and those weighing more than 2000 g. (p less than 0.001). The incidence was significantly influenced by mode of delivery, being highest in vaginal breech delivery followed in decreasing frequency by forceps and normal vaginal delivery. Among vaginal breech delivered neonates those weighing greater than or equal to 2500 g were at the highest risk. Evidence of foetal distress and meconium stained amniotic fluid had a low predictability of asphyxia being 35.0% and 40.0% respectively though both were statistically significant (p less than 0.001). PMID- 1937633 TI - Mother as a child health worker. AB - Mothers both in the clinics and at home do not receive the type of support they need from health workers, when their children fall sick. The majority of mothers are able to manage the scarce commodities such as food, health care and other basic needs in a poverty situation, quite effectively, the exceptions being during periods of stress. The odds that the mother has to struggle with in a poor environment, facing various types of discriminations, and later in her husband's household are analysed. A few examples are given about an improvement in mother's primary health care management skills. The "grass root" health workers should be available locally when the mothers need their help. The health workers should encourage the positive traditions prevailing. All effort should be made to increase the knowledge base of the husband as well as the peer group, so that the mothers continues to receive support in bringing about improvements. PMID- 1937636 TI - Child survival and child health development activities for the eighth five year plan in India (1900-1995)--III. Planning Commission, Government of India. PMID- 1937635 TI - Cardiopulmonary resuscitation; shock and dehydration; transportation issues. PMID- 1937634 TI - HLA-B5 and B21 antigens in aortoarteritis. AB - The distribution of class I HLA antigens (HLA-A, B) were determined in 50 patients of Aortoarteritis in an Indian population. This included 29 females and 21 males. The difference in antigen frequency was observed between patients and controls with reference to HLA-A19, B5 and B21 antigens. A decreased frequency of HLA-A19 was observed in the patients as compared to controls (14% vs 33.25%, X2 = 6.81, P less than 0.025). Of the B locus antigens, an increased frequency of HLA B5 was observed in the patients as compared to controls (48% vs 29.5%, X2 = 6.2, P less than 0.025). HLA-B21 was also increased in the patients as compared to the controls (18% vs 6.5%, X2 = 6.67, P less than 0.025). These data suggest the involvement of genetic factor (s) in the aetiopathogenesis of this disease. Further, the observations indicate that HLA-B5 and B21 may be associated with Aortoarteritis. PMID- 1937637 TI - On closing the gender gap: increasing the value of women in India. PMID- 1937638 TI - The girl child in India. PMID- 1937639 TI - Exercise testing in children: indications and technique. PMID- 1937640 TI - Taurine in infant nutrition. AB - The importance of taurine in diet is poorly understood. The present evidence suggests that it is a conditionally essential aminoacid in man wherein deficiency states may result in adverse changes which will be improved with supplementation. It has a role in fat absorption in preterm infants and children with cystic fibrosis, retinal dysfunction in patients receiving TPN and those with blind loop gut syndromes. Taurine is also reported to improve maturation of ABER in pre-term infants and has a role in osmoregulation of CNS and may act as neuroinhibitor. PMID- 1937641 TI - Management of extrahepatic portal hypertension in children. PMID- 1937642 TI - Environmental emergencies: burns, major trauma and near drowning. PMID- 1937643 TI - Intraosseous infusion: a re-discovered procedure as an alternative for pediatric vascular access. AB - The intraosseous infusion has numerous advantages over other techniques that provide vascular access during emergencies. It is a rapid and safe alternate route for fluid and certain drug administration in the infant or child. Few contra-indications or restrictions exist and the success rate for the technique is very high, even when performed by paramedical personnel, and the rate of complications is very low. At this time the technique should be reserved for children in crisis such as cardiac arrest, shock, trauma, life threatening status epilepticus, or any situation in which the potential benefit of rapid venous access outweighs the low incidence of complication. Intraosseous infusion is intended only for emergency resuscitation and stabilization, after which another route of vascular access should be sought. The technique may offer even more promise for those who rarely care for critically ill children, because this skill is easily mastered with even limited opportunity for practice. PMID- 1937644 TI - Ciprofloxacin in typhoid fever. AB - The study covers 78 children with typhoid fever who were hospitalized in April & May 1990. Serious complications were present in 32% (toxemia 22%, ileus 25% and myocarditis 8%). Blood cultures were positive in 30 of 49 tested. Others were diagnosed by positive Widal test. In vitro cultures of S. typhi were resistant to chloramphenicol (90%), ampicillin (93%) and co-trimoxazole (97%). However all were highly sensitive to ciprofloxacin and moderately sensitive to cephalexin and gentamycin. Ciprofloxacin alone or in combination was given in 73 of the 78 children and found to be remarkably effective in controlling the disease and preventing relapse. No serious side effects were noted. The cohort is being followed up for possible long term adverse effects. PMID- 1937646 TI - Knowledge of fresh medical graduates about immunization: impact of posting in community medicine. AB - Immunization being the most cost effective health intervention rightly forms an integral part of MCH health activities spectrum. Of late medical colleges in the country are directly involved from the planning to evaluation stages in the immunization programmes in their respective catchment areas. Immunization knowledge of 91 interns during their course of involvement in community work, was tested on the first day and last day of their three months posting in the Community Medicine Department. The study showed positive impact of training in the Department of Community Medicine on the performance levels of interns. This was found mainly attributable to effective interaction of interns with the community in the field and taking independent decisions as per the case requirements. PMID- 1937645 TI - Control of tetanus neonatorum in a rural area. AB - Experience in the control of tetanus neonatorum (TN) in a rural area is presented. TN was reduced by training of dais, increasing the coverage of tetanus toxoid to pregnant women and distribution of presterilized delivery kits to pregnant ladies for use by birth attendants. The problems of untrained birth attendants, effectiveness of tetanus toxoid coverage and place of delivery are discussed. PMID- 1937647 TI - Breastfeeding practices in Ethiopian women in southern California. AB - A retrospective study on the breastfeeding was carried out on selected 45 Ethiopian immigrant women living in the Los Angeles and San Diego areas (mean = 41 months; range 10-84 months). In-depth interviews were conducted to gather information on breastfeeding habits and a detailed analysis was made of the factors leading to the cessation of breastfeeding. The mean duration of breastfeeding in this sample was 4.2 +/- 1.1 months (range 3.0-5.7 months); and a non significant association was found between the length of residence in USA and the duration of breastfeeding (r = 0.189; 0.001 less than p less than 0.01 Pearson Correlation Matrix). Mothers breastfeeding less than four months (N = 27) were compared to mothers who breastfed longer than four months (N = 18). A statistically significant association was found between the duration of breastfeeding and the following variables: mother's level of education (X2 = 20.12 p less than 0.005, df = 1), source of income (X2 = 13.46, p = 0.001, df = 1)' and the availability of free sample formula form the hospital (X2 = 4.46 p = 0.035, df = 1). The most common cited reasons for stopping breastfeeding were mother's employment (40%), and mother's lack of milk (32%). Data suggest here that the Ethiopian immigrant women in this selected sample are not following the trends towards breastfeeding in the United States. PMID- 1937648 TI - Empowering young girls for health and development. AB - Yuvati Vikas Kendra (YVK) model of empowering young girls in the age bracket of 7 19 years could raise the level of awareness and generate self-esteem and self confidence in over 50% of young girls over a period of six months of operation. The YVK model was utilised by 37-55% of enrolled girls in different age brackets; thus these centres functioned well below their installed capacity. Functional inter-sectoral linkages have to be developed for better impact and better coverage. Data based information from other models of empowerment such as schools, non-formal system of education and Integrated Child Development Services Scheme, is called for to choose different alternatives for our country, as no uniform system can succeed in this vast country. Diversified modes and approaches for empowerment of young girls are needed. PMID- 1937649 TI - Neural tubal defects in an east Delhi hospital. AB - A high incidence of congenital neural tube defects was suspected among the babies born in East Delhi. The hospital data of 30 months was reviewed to find out the incidence and to evaluate the prenatal diagnosis in these disorders. An incidence of 7/1000 births was found to be correct in all cases of anencephaly and hydrocephalus. However, spina bifida and encephalocele were missed in 25% of cases. All patients were diagnosed late during pregnancy mainly because of late booking. Early booking and a high index of suspicion are desirable for early prenatal diagnosis. PMID- 1937650 TI - Association of congenital heart disease and urinary tract malformations. PMID- 1937652 TI - Leigh's subacute necrotizing encephalomyelopathy: possible diagnosis by C.T. scan. PMID- 1937651 TI - Cholestatic jaundice caused by trimethoprim. PMID- 1937653 TI - Congenital filarial lymphoedema. PMID- 1937654 TI - The role of spleen in post-transfusion malaria in thalassaemia patients. PMID- 1937655 TI - Spontaneous duodenal perforation in neonates. PMID- 1937656 TI - "Pyridoxine supplementation with isonex--is it necessary?". PMID- 1937657 TI - Prenatal diagnosis of pre-sacral mass, simulated by meconium. PMID- 1937658 TI - Adenosine, the heart, and coronary circulation. AB - Adenosine is known to regulate myocardial and coronary circulatory functions. Adenosine not only dilates coronary vessels, but attenuates beta-adrenergic receptor-mediated increases in myocardial contractility and depresses both sinoatrial and atrioventricular node activities. The effects of adenosine are mediated by two distinct receptors (i.e., A1 and A2 receptors). A1 adenosine receptors, located in atrial and ventricular myocardium and sinoatrial/atrioventricular nodes, are responsible for inhibition of adenylyl cyclase activity. A2 adenosine receptors, located in coronary endothelial and smooth muscle cells, are responsible for stimulation of this enzyme activity. During increased myocardial oxygen demand due to rapid pacing and exercise, although both coronary blood flow and adenosine concentrations in the myocardium and coronary efflux increased, there is no clear consensus explaining its cause and effect relation at present. However, ischemia/reperfusion-induced coronary hyperemia is believed to be mostly attributed to released adenosine, and it has been proven that adenosine attenuates the severity of ischemia due to its coronary vasodilatory action. The beneficial effects of adenosine during ischemia/reperfusion processes do not seem simple. This is because myocardial ischemia and reperfusion injury is caused by 1) activated leukocytes and platelets, 2) ATP depletion and calcium overload of myocardium, and 3) catecholamine release from the presynaptic nerves as well as 4) the impaired coronary circulation. Intriguingly adenosine attenuates all of these deleterious actions and thereby attenuates ischemia/reperfusion injury. Indeed, adenosine attenuates the severity of contractile dysfunction (myocardial stunning) and limits the infarct size. Thus, administration of adenosine or potentiators of adenosine production in the ischemic myocardium may be beneficial for the attenuation of ischemic and reperfusion injuries, although further clinical investigations are necessary. PMID- 1937659 TI - Exercise training lowers resting renal but not cardiac sympathetic activity in humans. AB - Endurance exercise training has previously been shown to reduce the plasma concentration of norepinephrine. Whether reduction in sympathetic activity is responsible for the blood pressure-lowering effects of exercise training is unknown. Using a radiotracer technique, we measured resting total, cardiac, and renal norepinephrine spillover to plasma in eight habitually sedentary healthy normotensive men (aged 36 +/- 3 years, mean +/- SEM) after 1 month of regular exercise and 1 month of sedentary activity, performed in a randomized order. One month of bicycle exercise 3 times/wk (40 minutes at 60-70% maximum work capacity) reduced resting blood pressure by 8/5 mm Hg (p less than 0.01) and increased maximum oxygen consumption by 15% (p less than 0.05). The fall in blood pressure was attributable to a 12.1% increase in total peripheral conductance. Total norepinephrine spillover to plasma was reduced by 24% from a mean of 438.8 ng/min (p less than 0.05). Renal norepinephrine spillover fell by an average of 41% from 169.4 ng/min with bicycle training (p less than 0.05), accounting for the majority (66%) of the fall in total norepinephrine spillover. Renal vascular conductance was increased by 10% (p less than 0.05), but this constituted only 18% of the increase in total peripheral conductance. There was no change in cardiac norepinephrine spillover. The reduction in resting sympathetic activity with regular endurance exercise is largely confined to the kidney. The magnitude of the fall in renal vascular resistance, however, is insufficient to directly account for the blood pressure-lowering effect of exercise, although other effects of inhibition of the renal sympathetic outflow may be important. PMID- 1937660 TI - Effect of regular exercise on 24-hour arterial pressure in older hypertensive humans. AB - The experimental goals were to determine if regular low-intensity aerobic exercise reduces 24-hour arterial blood pressure in middle-aged and older (aged 50 years or older) humans with mild diastolic (90-105 mm Hg) essential hypertension and, if so, whether this is accurately reflected by changes in casual recordings made at rest. Fourteen subjects walked 3-4 days/wk for 6 months, with 10 exercising an additional 6 months; 12 other subjects served as nonexercising controls. In the exercising subjects, maximal oxygen consumption increased 7-14% (p less than 0.05) with little or no change in body weight or fat. Conventional casual readings of systolic, mean, and diastolic arterial pressure at rest were lower (5-10 mm Hg, p less than 0.05) in all body positions after 6 months of exercise and changed little thereafter. Casual recordings made during additional circulatory measurements showed 6-month decreases of only half this magnitude and were specific to a particular blood pressure phase and body position; however, all changes were significant after 12 months of exercise. The reductions in arterial pressure at rest were associated with decreases in heart rate (p less than 0.05) and cardiac output (p less than 0.05). Ambulatory determined 24-hour arterial pressure was unchanged after 6 months of exercise, but mean levels were slightly lower (4 mm Hg, p less than 0.05) after 12 months due to reductions in daytime (7 mm Hg, p less than 0.05) and nighttime (4 mm Hg, NS) systolic pressure; diastolic pressure was unchanged throughout the year of training. In the controls, conventionally recorded casual blood pressure levels were lower after 6 months (p less than 0.05), but no other changes were observed in any other variable over the 12 months of study. We conclude 1) regular low intensity aerobic exercise at best produces only small reductions in 24-hour levels of arterial pressure in middle-aged and older humans with mild (diastolic) essential hypertension and 2) training-associated changes in casually determined blood pressure at rest are dependent on the measurement conditions and, most importantly, do not necessarily reflect the magnitude or even the direction of changes in arterial pressure throughout an entire day. PMID- 1937661 TI - Effect of unrestricted activity on accuracy of ambulatory blood pressure measurement. AB - A validation study of the Takeda TM-2420 ambulatory blood pressure recorder was performed on 10 subjects using the Oxford ambulatory intra-arterial recording apparatus during unrestricted activity. Electronic linkage of the two recorders ensured simultaneous blood pressure readings, taken from opposite arms. Although there was close approximation of intra-arterial and automated sphygmomanometric recordings over the range of blood pressure encountered in this study, there was a wide scatter of points and a tendency for the machine to underestimate systolic pressure by more than 15 mm Hg in the hypertensive range (systolic blood pressure more than 160 mm Hg) was detected. These findings suggest that automated recording of blood pressure during unrestricted activity may have a proportion of artifactual readings. Although simultaneous intra-arterial blood pressure recording may not be appropriate for widespread use in device validation, this study illustrated some potential disadvantages of the current validation recommendations, namely, the absence of assessment of device accuracy during unrestricted and ambulatory activity. PMID- 1937662 TI - Risk factors for hypertension in a national cohort study. AB - Hypertension continues to be a major public health problem in the United States. We used data from the National Health and Nutrition Examination Survey Epidemiologic Followup Study (1971-1984) to examine predictors of hypertension for the 7,073 participants free from hypertension at the baseline examination. The follow-up period averaged 10 years. Body mass index was positively related to the probability of hypertension developing among white men (n = 2,370), white women (n = 3,949), black men (n = 231), and black women (n = 523). Education was inversely associated with the probability of hypertension developing among white women and was of borderline significance among white men and black women. In a subanalysis of white men (n = 1,790) and white women (n = 3,063) who completed the 24-hour recall dietary questionnaire, dietary consumption of sodium, calcium, and potassium did not predict the development of hypertension. The failure of our study to support findings relating intake of dietary cations to the development of hypertension may be attributable to imprecision in the measurement of dietary data and misclassification of hypertension status. These data reinforce the importance of weight control in the primary prevention of hypertension. PMID- 1937663 TI - Boiled coffee and blood pressure. A 14-week controlled trial. AB - The question of whether long-term elimination of coffee from the diet lowers blood pressure has not been settled. Consumption of Scandinavian-style "boiled coffee" is associated with coronary heart disease. However, little is known about the effect of brewing method on the blood pressure-raising potential of coffee. We have studied the effects on blood pressure and heart rate of total elimination of coffee and tea in comparison with drinking boiled coffee consumed as such, or boiled coffee consumed after filtration through paper filter. Thirty-one women and 33 men first consumed 6 cups/day of boiled and filtered coffee for 17 days. Then they were randomly divided into three groups, which for the next 79 days received either unfiltered boiled coffee (caffeine content 860 mg/l), boiled-and filtered coffee (887 mg caffeine/l), or no coffee, the latter being replaced by fruit juice and mineral water. Total elimination of coffee did not significantly affect blood pressure or heart rate relative to boiled-and-filtered coffee. In subjects who drank boiled coffee, mean ambulant systolic blood pressure rose significantly relative to those who consumed boiled-and-filtered coffee (mean difference +/- SEM, 3.1 +/- 1.1 mm Hg, p = 0.006). This response showed a tendency to be stronger for women (4.5 +/- 1.8 mm Hg) than for men (1.7 +/- 1.2 mm Hg). We conclude that elimination of filtered coffee has no substantial long term effect on blood pressure, but consumption of unfiltered boiled coffee may cause a slight but significant rise in systolic blood pressure. PMID- 1937664 TI - High urinary dopa and low urinary dopamine-to-dopa ratio in salt-sensitive hypertension. AB - Dopamine in urine is derived substantially from renal uptake and decarboxylation of 3,4-dihydroxyphenylalanine (dopa), and increases in excretion of dopa normally parallel increases in excretion of dopamine during salt loading. Since patients with salt-sensitive hypertension may have decreased urinary excretion of dopamine during dietary salt loading, the present study was designed to evaluate the response of dopa to salt loading. Sixteen inpatients with normal-renin essential hypertension ate a constant metabolic diet containing 9 mmol/day sodium for 7 days, followed by the same diet but containing 249 mmol/day sodium for 7 days. Salt sensitivity was defined as an increase in mean arterial pressure of 8 mm Hg between the diets; on this basis, nine patients were salt-sensitive and seven, salt-resistant. The rate of urinary dopa excretion was significantly higher in the salt-sensitive patients throughout the study (mean rates 132 +/- 13 nmol/day in the salt-sensitive group and 78 +/- 9 nmol/day in the salt-resistant group for the 14 days of observation, p less than 0.01). When dietary sodium intake was increased to 249 mmol/day, urinary dopa excretion increased significantly more in salt-sensitive patients than salt-resistant patients. At the end of the high salt diet, dopamine excretion was significantly attenuated in the salt-sensitive patients, despite higher rates of dopa excretion. Thus, the urinary ratio of dopamine to dopa was decreased in salt-sensitive patients, regardless of salt intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937665 TI - Role of chloride in angiotensin II-induced salt-sensitive hypertension. AB - The present study investigated the effect of the anion accompanying sodium on the development of angiotensin II-induced hypertension in rats and the role of the sympathetic nervous system and extracellular fluid volume in its mechanism. Hypertension was induced by intraperitoneal infusion of angiotensin II (125 ng/min) for 12 days via miniosmotic pump. High dietary intake of sodium chloride significantly augmented the angiotensin II-induced hypertension (mean blood pressure on day 13, 165 +/- 6 versus 142 +/- 6 mm Hg, p less than 0.05), but equimolar sodium loading provided as sodium citrate failed to enhance angiotensin II hypertension (140 +/- 6 mm Hg). Plasma norepinephrine concentration in the conscious, resting state increased with sodium chloride loading in angiotensin II infused rats (594 +/- 42 versus 312 +/- 37 pg/ml, p less than 0.01), but it remained unchanged with sodium citrate loading (324 +/- 23 pg/ml). Correspondingly, maximum response to hexamethonium bromide, a ganglion blocker, was greater in sodium chloride-loaded angiotensin II rats (77.7 +/- 4.6 mm Hg) than that in angiotensin II (59.7 +/- 5.1 mm Hg) or in sodium citrate-loaded angiotensin II (57.7 +/- 4.2 mm Hg) rats. Moreover, extracellular fluid volume, measured as Na2(35)SO4 space, increased in sodium chloride-loaded angiotensin II rats (427 +/- 18 ml/kg body wt) as compared with that in angiotensin II rats (375 +/- 15 ml/kg body wt) but not when compared with volume in sodium citrate-loaded angiotensin II (389 +/- 7 ml/kg body wt) rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937666 TI - Abnormalities of carbohydrate and lipid metabolism in Dahl rats. AB - Plasma glucose, insulin, and triglyceride concentration, blood pressure, and insulin action on isolated adipocytes were determined in weight-matched Sprague Dawley, Dahl salt-resistant, and Dahl salt-sensitive rats. Blood pressure and plasma glucose concentrations were not significantly different in the three groups. However, Dahl salt-sensitive rats had significantly higher plasma insulin (39 +/- 2 microunits/ml) and triglyceride (213 +/- 11 mg/dl) concentrations than did Sprague-Dawley rats (27 +/- 2 microunits/ml and 101 +/- 6 mg/dl, respectively). Values for insulin (34 +/- 4 microunits/ml) and triglyceride (159 +/- 11 mg/dl) were intermediate in Dahl salt-resistant rats. In contrast, maximal insulin-stimulated glucose transport was significantly lower in adipocytes isolated from Dahl salt-sensitive as compared with Sprague-Dawley rats (400 +/- 16 versus 523 +/- 14 fl/cell/sec), with Dahl salt-resistant rats again having intermediate values. However, the ability of insulin to maximally inhibit catecholamine-stimulated lipolysis was similar in all three groups, averaging approximately 20% of the activity present in the absence of insulin. All of these differences were seen when the rats were eating conventional chow and did not change in Dahl rats after 2 weeks of an 8% NaCl diet. On the other hand, the predicted rise in blood pressure took place in Dahl salt-sensitive rats, increasing from 147 +/- 4 to 181 +/- 6 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937667 TI - Metabolic abnormalities of hypertension. A lesson in complexity. PMID- 1937668 TI - Mechanical pressure versus intrinsic effects of hypertension on large arteries in humans. AB - Brachial artery diameter and compliance were measured in 23 normotensive control subjects and 49 hypertensive patients. The results were compared in isobaric conditions by a modeling analysis extrapolating from the measured data a short segment of the pressure-diameter and pressure-compliance curves in the artery. A logarithmic diameter-pressure function was used as well as measurements of brachial artery blood pressure and lumen diameter (by pulsed Doppler), and of brachial-to-radial pulse wave velocity (by mechanography). The measured values of diameter and compliance in the hypertensive patients were 109% and 63%, respectively, of the control group values. By extrapolating the data via the model at the same pressure level in all subjects (the average level of mean blood pressure of the two groups), the isobaric values of diameter and compliance in the hypertensive patients were 107% and 81%, respectively, of the control group values. Overall, measured isobaric diameters and measured compliance correlated with systolic, diastolic, and mean blood pressure values (p less than 0.001), whereas isobaric compliance correlated only with systolic (p less than 0.05) and pulse (p less than 0.01) pressure values. Thus, the increased diameter and reduced compliance of the brachial artery observed in hypertensive humans cannot be attributed solely to the stretching effect of elevated blood pressure, but also to intrinsic alteration of the arterial walls. These could represent either adaptative structural or functional changes secondary to the chronic increase in arterial pressure, or primary abnormalities of the vessel wall. PMID- 1937669 TI - Postprandial hypotension. Pathophysiological mechanisms and clinical implications in different disorders. PMID- 1937670 TI - Angiotensinogen: an attractive and underrated participant in hypertension and inflammation. PMID- 1937671 TI - The First Irvine H. Page International Hypertension Research Symposium: the Page Mosaic. Baltimore, Maryland, September 11-12, 1990. Proceedings. PMID- 1937672 TI - Genetic basis of hypertension. The renin-angiotensin paradigm. PMID- 1937673 TI - Endothelium and growth factors in vascular remodeling of hypertension. AB - The pioneering work of Furchgott, Moncada, and Vane has clearly established that the endothelium plays a critical role in the regulation of vascular tone. The endothelium produces several potent vasoactive substances, including vasodilators such as endothelium-derived relaxing factor and prostacyclin as well as vasoconstrictors such as angiotensin II and endothelin. These vasoactive substances not only have short-term effects on vascular tone but also appear to induce long-term effects on vascular structure. This process of vascular remodeling involves cell growth or regression and extracellular matrix expansion or contraction. As the interface between the bloodstream and the vessel wall, the endothelium plays a pivotal role in sensing and transducing the stimulus that induces vascular remodeling as well as producing the mediators that alter cell growth and the composition of the extracellular matrix. The endothelium maintains homeostasis within the vasculature by a balance between vasodilators and vasoconstrictors or growth inhibitors and growth promoters. Endothelial cell dysfunction may alter the delicate balance of mediators necessary to maintain homeostasis. Indeed, endothelial cell dysfunction is a common pathogenetic defect in animal models of hypertension as well as in hypertensive humans. Further understanding of the cellular and molecular mechanisms of vascular remodeling induced by endothelial cell-derived mediators may have important implications in the pathogenesis and treatment of hypertension. PMID- 1937674 TI - Angiotensin I and II. Some early observations made at the Cleveland Clinic Foundation and recent discoveries relative to angiotensin II formation in human heart. AB - The renin-angiotensin system originally was thought to be responsible for only renovascular hypertension, but the development and use of various inhibitors of this system have produced much evidence for its participation in many forms of hypertensive disease. Tissue renin-angiotensin system also may play a major role in blood pressure control. Chronic clinical as well as animal use of converting enzyme inhibitors results in levels of angiotensin II that are equivalent to those found in the normotensive state and higher than those found in the very acute phase of treatment. The source of this conversion possibly may be due to enzymes unrelated to angiotensin converting enzyme. One such enzyme is a very highly specific serine protease isolated from human cardiac tissue. This enzyme exists in human ventricular tissue at levels four to five times that of angiotensin converting enzyme. During chronic treatment of patients with heart failure, angiotensin I levels become high, and heart tissue levels of angiotensin II may become elevated because of the conversion to angiotensin II by this serine protease. This conversion in turn may possibly increase inotropy of the heart, whereas the peripheral resistance remains low because of the reduction of angiotensin II in the circulation. PMID- 1937676 TI - Angiotensin converting enzyme inhibitors. An overview. PMID- 1937675 TI - Angiotensin-(1-7): a new hormone of the angiotensin system. AB - We provide a new foundation for an alternative interpretation of the biochemical physiology of the brain and other tissue angiotensin systems on the basis of research done in our laboratory. This perspective is prompted by the discovery that angiotensin-(1-7) has cellular functions that differ from those established for angiotensin II. Although angiotensin-(1-7) is not an agonist in terms of activating vasoconstriction, stimulating thirst, or promoting aldosterone release, the heptapeptide caused neuronal excitation and vasopressin release with a potency similar to that found with angiotensin II. Furthermore, angiotensin-(1 7) enhances the production of prostanoids by a receptor-mediated event that causes no associated rise in intracellular Ca2+. These actions of angiotensin-(1 7) provide a new understanding of the heterogeneous functions of angiotensin peptides as modulators of a wide range of regulatory functions in mammals. PMID- 1937677 TI - Angiotensin II receptor antagonists. From discovery to antihypertensive drugs. AB - Some simple N-benzylimidazoles, originally described by Takeda Chemical Industries (Osaka, Japan), were characterized to be very weak but selective nonpeptide angiotensin II (Ang II) receptor antagonists with a competitive mode of action. Chemical modifications of these led to EXP6155 and EXP6803, which showed approximately 10- and 100-fold higher affinity, respectively, but were orally ineffective. Oral activity was obtained for the biphenyl carboxylic acid derivatives EXP7711 and especially EXP9654. A further advance in the design of nonpeptide Ang II receptor antagonists was provided by DuP 753, an analogue of EXP7711 in which the carboxylic acid function is replaced by its tetrazol-5-yl equivalent. DuP 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5 yl)bi phe nyl-4- yl)methyl]imidazole, potassium salt) displaces radiolabeled Ang II from its specific binding sites in various tissues, affording IC50 values of approximately 20 nM. DuP 753 competitively antagonizes Ang II-induced responses in various in vitro and in vivo preparations but does not influence those to KCl, norepinephrine, vasopressin, and others, nor does it affect converting enzyme and renin. In high renin animal models of elevated arterial blood pressure, intravenous and oral administrations of DuP 753 produce a sustained decrease in pressure without influencing heart rate. Marked antihypertensive effects are observed in spontaneously hypertensive rats, but no efficacy is noticed in deoxycorticosterone acetate hypertensive animals. DuP 753 showed no agonistic properties in any of the above test systems and has been chosen to undergo clinical trials for the treatment of hypertension. In rats, the 5-carboxylic acid (EXP3174) represents a major metabolite of DuP 753.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937678 TI - Functional derangements in the regulation of aldosterone secretion in hypertension. AB - Excess production of aldosterone secondary to an adrenal tumor or bilateral hyperplasia is a known, but infrequent, cause of hypertension. A more frequent adrenal abnormality, observed in 30-40% of hypertensive patients, is a functional derangement in aldosterone secretion. Two such conditions have been described: low renin essential hypertension and non-modulating essential hypertension. Both have in common 1) an abnormality in the interaction of angiotensin II (Ang II) with the adrenal and 2) sodium sensitivity of the blood pressure. However, the pathophysiological mechanisms for the sodium sensitivity and hypertension are different. In normal subjects, the response of the adrenal glomerulosa cell to Ang II varies with the level of sodium intake, with sodium restriction enhancing the response. In one group of hypertensive patients with low plasma renin levels, the normally reduced aldosterone responses to Ang II on the high salt diet do not occur. Thus, these individuals have an enhanced adrenal response to Ang II under circumstances in which it should be reduced, thereby leading to lower renin levels and a tendency toward sodium retention. The second group has the opposite defect; that is, on a low sodium diet, they have a reduced adrenal response to Ang II. This results in a normal or high plasma renin level. The sodium sensitivity of their blood pressure arises not from the adrenal abnormality but from the associated defect in sodium-dependent, Ang II-mediated changes in renal blood flow. Thus, on a high salt diet, these patients, who are termed "non modulators," fail to increase renal blood flow, thereby leading to a sodium retaining state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937679 TI - Arachidonate metabolites and kinins in blood pressure regulation. AB - Arachidonic acid (AA) can be metabolized to an array of products affecting biological mechanisms such as those governing vascular reactivity and transport function. Metabolism of AA by cyclooxygenase in the nephron is discretely localized and is overshadowed in some nephron segments by a considerable capacity to generate P-450 AA metabolites. The synthesis of renal P-450 AA products is increased in hypertension. AA metabolites participate in fluid and electrolyte homeostasis and regulation of tissue blood flow and act as modulators of pressor systems. In addition, eicosanoids either augment or mediate the vasodilator diuretic actions of the kallikrein-kinin system. PMID- 1937680 TI - Medullipin system. Generation of medullipin II by isolated kidney-liver perfusion. AB - Perfusion of isolated normal rat kidneys with blood at elevated blood pressure (180-200 mm Hg) followed by perfusion of the renal perfusate through an isolated normal rat liver under venous pressure yielded in the plasma of the hepatic effluent a vasodepressor lipid having the chromatographic and biological characteristics of medullipin II. These findings support the view that medullipin II is the final product of the renohepatic axis of blood pressure control. PMID- 1937681 TI - Unifying hypothesis of sodium and water regulation in health and disease. AB - Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome, and pregnancy. Nonosmotic vasopressin release has been implicated in the water retention of these edematous disorders. The nonosmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems in both experimental animals and in edematous patients. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin and activation of the renin-angiotensin system. These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. Neither total extracellular fluid volume nor blood volume is a determinant of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by a decrease in effective arterial blood volume (EABV) due to either a fall in cardiac output or peripheral arterial vasodilation. The acute response to a decrease in EABV involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The resultant renal vasoconstriction limits the distal tubular delivery of sodium and water, thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated glomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium and water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation. PMID- 1937682 TI - Roles of sodium, potassium, calcium, and natriuretic factors in hypertension. AB - This review first summarizes evidence from animals and humans for and against a role for dietary sodium in the genesis and treatment of hypertension. The evidence for its role is strongest in those subjects with impaired ability to excrete sodium because of organic renal disease or mineralocorticoid excess. Here, restriction of dietary sodium promptly lowers pressure. Its role in the genesis of essential hypertension is more controversial. Nevertheless, it appears that some patients with mild to moderate essential hypertension respond to moderate sodium restriction with a modest fall in pressure. This restriction also seems to reduce the amount of antihypertensive medication needed to keep pressure under control. Next, the mechanism of the pressure response to dietary sodium chloride is considered, with emphasis on potassium depletion and increased plasma levels of prohypertensive sodium pump inhibitor and antihypertensive atrial natriuretic peptide. The evidence for a primary role for dietary potassium in the genesis of hypertension then is summarized; certain subsets of subjects with a high incidence of hypertension also have a lower potassium intake. Some investigators have found that dietary potassium supplementation lowers pressure in established hypertension. This may result from natriuresis and from vasodilation subsequent to stimulation of Na+,K(+)-ATPase in vascular smooth muscle and adrenergic nerve terminals. After the role of dietary calcium is discussed, practical aspects of dietary sodium restriction and dietary potassium supplementation in the therapy for established hypertension are considered. The review concludes with comments on their possible roles in the prevention of hypertension. PMID- 1937683 TI - Pathogenesis of essential hypertension. A link between dietary salt and high blood pressure. PMID- 1937685 TI - Role of the baroreceptor reflexes in circulatory control, with particular reference to hypertension. PMID- 1937684 TI - Role of sympathetic efferent nerves in blood pressure regulation and in hypertension. AB - This article presents some aspects of the role of sympathetic efferent nerves in the regulation of blood pressure in humans. Lessons have been learned from disorders that cause either sympathetic underactivity or overactivity. In chronic autonomic failure, pressor stimuli (mental arithmetic, isometric exercise, or cold) are unable to raise blood pressure, whereas stimuli that normally activate sympathetic efferent nerves to maintain blood pressure (head-up tilt, exercise, and food ingestion) can cause marked hypotension. Recognition of specific defects, such as the inability to synthesize norepinephrine in isolated dopamine beta-hydroxylase deficiency, suggests that sympathetic nerves may influence blood pressure regulation through nonadrenergic mechanisms (dopamine, neuropeptides, and purines). Tetraplegic patients with high cervical cord transection also have sympathetic impairment and postural hypotension, but this is less of a clinical problem because of compensatory hormonal and other mechanisms. Tetraplegic patients are unique as they also may have severe paroxysmal hypertension because of increased spinal sympathetic reflex activity. The pathophysiological mechanisms responsible for this exaggerated response include changes in postsynaptic adrenergic receptor numbers and their sensitivity, the actions of nonadrenergic cotransmitters, and the lack of sympathoneural pathways from the brain that are severed by the lesion. Finally, the putative role of the sympathetic nervous system in hypertension with unilateral renal artery stenosis, which initially is humorally mediated, is discussed. The centrally acting sympatholytic agent clonidine is effective in lowering blood pressure in renovascular hypertension independently of humoral factors when multiple agents have failed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937686 TI - Abnormal renal function and autoregulation in essential hypertension. AB - The goal of this presentation has been to emphasize two fundamental mechanisms in the development of essential hypertension. These are: 1) The basic cause of essential hypertension is the inability of the kidneys to excrete an adequate volume of urine at normal arterial pressure. Therefore, fluid accumulates in the body until the pressure rises high enough to balance fluid output with fluid intake. This fluid balancing act is an infinite gain feedback system for controlling arterial pressure to a very precise level determined by the kidneys. Furthermore, this infinite gain allows the kidney mechanism to dominate the other pressure control mechanisms for long-term pressure control. Because of this domination, as long as a person has normal intake of water and electrolytes, essential hypertension cannot develop without an elevated pressure setting of the kidneys. 2) An increase in total peripheral resistance will not cause hypertension as long as the kidneys can still excrete normal amounts of water and electrolytes at normal arterial pressure, because loss of excess fluid volume at high pressures will simply reduce the cardiac output until the pressure falls back to normal. Therefore, what is the cause of the very high total peripheral resistance found in almost all patients with essential hypertension? The answer is likely the long-term blood flow autoregulation mechanism that occurs in virtually all tissues of the body. That is, when the pressure rises too high for whatever reason, this in turn forces too much blood flow through the tissues. In response, the local blood flow control mechanisms all over the body increase the vascular resistances until the flows return to normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937687 TI - Twenty-year follow-up of hemodynamics in essential hypertension during rest and exercise. AB - Central hemodynamics were studied invasively (blood pressure intra-arterially and cardiac output by dye-dilution method) at rest and during exercise in men with essential hypertension and in age-matched normotensive controls. At the start of the study, resting cardiac index, heart rate, oxygen consumption, and mean arterial pressure were approximately 15% higher in those hypertensive patients aged 17-29 years than in normotensive subjects, whereas total peripheral resistance index was similar in both groups. During exercise, the stroke index was reduced and total peripheral resistance index was increased in the hypertensive group. After 10 and then 20 years, central hemodynamics were restudied in the hypertensive patients. The initially high cardiac index/normal total peripheral resistance index pattern changed to a low cardiac index/high resistance pattern at 10- and 20-year follow-up. In 25 patients initially aged 40 49 years, treatment with diuretics, beta-blockers, or a combination of the two normalized diastolic pressure. In spite of adequate blood pressure control, a marked increase in total peripheral resistance and fall in cardiac index and stroke index were also seen in this age group treated over 20 years. The study has shown a progressively abnormal hemodynamic pattern over two decades in patients of different ages with essential hypertension. PMID- 1937688 TI - Pathophysiology of the vasculature in hypertension. AB - The vessel wall is thicker in hypertension. Folkow demonstrated that adaptive structural changes occur in vessels in response to the increased wall stress of hypertension. Because the vessel wall thickens and encroaches on the lumen, the adaptive change results in an elevated vascular resistance. It also exaggerates the vasoconstrictor effects of vascular smooth muscle contraction, thereby increasing vascular reactivity to physiologically occurring vasoactive agents. As solid as this information may be, important unanswered questions still remain related to the question "What makes the pressure go up in the first place?" In this brief review, we have examined possible culprits both in the area of extrinsic vascular regulatory systems and in that of intrinsic changes in the vascular smooth muscle cell. Interesting newly described vasoactive agents currently are being evaluated. On the other hand, generalized intrinsic abnormalities in the cell membrane are well documented in hypertension. Many individual transport systems display this abnormality, suggesting that the primary defect may be in the lipid bilayer that influences the function of all integral protein transport systems. Abnormalities also have been found in the cells' signal transduction systems, whereas the energy metabolism and contractile protein system are essentially normal. Functional abnormalities of the vascular smooth muscle cell in hypertension must explain both its increased contraction and its increased growth. It is likely that the same functional abnormality may explain both of these changes. PMID- 1937689 TI - Central nervous system and the pathogenesis of hypertension. Sites and mechanisms. AB - A large body of evidence indicates that the central nervous system plays an essential role in the pathogenesis of hypertension. However, in many cases the specific brain regions involved and the mechanisms by which these regions promote hypertension are not known. In recent years, research in this and other laboratories has attempted to determine the mechanisms by which neural and humoral signals arising in response to pathological conditions (often occurring in the periphery) interact with the central nervous system to produce hypertension. In this article, we illustrate the coupling of peripheral and central factors in the pathogenesis of hypertension by examining the central actions of angiotensin II and mineralocorticoids in the expression of renal hypertension and mineralocorticoid-salt hypertension, respectively. We also review recent data from this laboratory illustrating the involvement of medullary vasomotor centers in the development of neurogenic hypertension after sinoaortic deafferentation and in the maintenance of hypertension in the spontaneously hypertensive rat. PMID- 1937690 TI - Endothelium-derived vasoactive factors: I. Endothelium-dependent relaxation. AB - Evidence continues to accumulate on the importance of paracrine substances formed in the vascular endothelium in the regulation of the vascular system. Those that relax the underlying smooth muscle include nitric oxide, prostacyclin, and an unidentified hyperpolarizing factor; those causing contraction include angiotensin II, endothelin, oxygen-derived free radicals, prostacyclin H2, and thromboxane A2. Determination of the mechanisms governing the formation and release of these substances in different blood vessels of the same species and in different species as well as the maintenance of the balance between them is important for understanding their role in normal circumstances and in diseases of the blood vessels. In this article, we will summarize the current understanding of the role of endothelium-derived relaxing factors and discuss the possibility that endothelial dysfunction may play a primary as well as a secondary role in the pathogenesis of primary hypertension. As a consequence of this dysfunction, substances formed in the endothelial cells at the sites of the arterial baroreceptors could lead to their resetting, resulting in less inhibition of the vasomotor centers, enhanced neurohumoral activity, and a consequential increase in systemic vascular resistance. This increase could be enhanced by a predominant action of endothelium-derived contracting factors in the resistance vessels. Proliferation of the vascular smooth muscle would follow, because of the mitogenic action of some of these factors and other growth promotors. By these mechanisms, the endothelium may participate in the polygenic dysfunction characteristic of primary hypertension, not only in initiating the increase in arterial blood pressure, but also in sustaining it. PMID- 1937691 TI - Endothelium-derived vasoactive factors: II. Endothelium-dependent contraction. AB - Endothelial cells may produce and release vasoconstrictor substances in response to a number of agents and physical stimuli. In this brief review, current understanding of the mechanisms of endothelium-dependent contractions will be discussed. Cyclooxygenase products of arachidonic acid metabolism including thromboxane A2, prostaglandin H2, superoxide anions, vasoconstrictor peptide endothelin-1, and unidentified factor released from endothelium by hypoxia may mediate these contractions. The physiological role of endothelium-dependent contractions in regulation of the cardiovascular system is unknown. Existing evidence supports the concept that contracting factors may become important regulators of vascular tone under pathological conditions. We speculated about the possible importance of endothelium-dependent contractions for venous graft function, development of vasospasm, increased vascular resistance in hypertension, and vascular complications in diabetes. PMID- 1937692 TI - Polycations induce microvascular leakage of macromolecules in hamster cheek pouch. AB - The microvascular response to two polycationic proteins, poly-L-lysine (mol wt 104,000) and leukocyte elastase, was studied in the hamster cheek pouch microcirculation model. A 2-min topical application of polylysine (100 micrograms/ml) induced vigorous macromolecular leakage from venules only that declined within 30 min. A second application induced significantly less leakage. The leakage was inhibited by admixing polylysine with dextran sulfate prior to application or by giving hamsters an intravenous injection of dextran sulfate. The histamine antagonist pyrilamine did not interfere with the leakage, and only a few degranulated mast cells were found after polylysine application. No intravascular adhesion of leukocytes could be detected. Elastase (100 micrograms/ml) was deposited adjacent to venules with micropipets. The resulting leakage response was not inhibited by L658,758, an inhibitor of elastase enzymatic activity, but by dextran sulfate. These results may prove significant in light of the numerous polycationic proteins present within neutrophil granules. PMID- 1937693 TI - Cellular inflammation of fetal excisional wounds: effects of amniotic fluid exclusion. AB - The development of an cellular inflammatory response secondary to mechanical wounding has not been observed previously in the fetus. The effect of amniotic fluid exclusion on the inflammatory response in fetal rabbits subjected to full thickness dorsal excisional wounds on day 25 of gestation (term = 31-32) was examined. The fetuses were either returned immediately to the uterus; a silicone cover was sutured over the wound; or a silicone cover with a centrally located hole was sutured over the wound. Seventy-two hours after wounding, uncovered wounds (19 live fetuses) exhibited only occasional inflammatory cells. Covered wounds (14 live fetuses) showed a pronounced cellular inflammatory response. Partially covered wounds (six live fetuses) showed a peripheral, intermediate response. The findings suggest that amniotic fluid contains factors inhibitory to inflammation, which the cover effectively excludes. PMID- 1937696 TI - Rights of the consumer and the role of consumer societies. PMID- 1937694 TI - Interaction between human neutrophils and corneocytes: corneocyte-induced respiratory burst of neutrophils assessed by chemiluminescence. AB - In an in vitro study to examine whether corneocytes stimulate neutrophils to cause a respiratory burst, we found that stratum corneum (SC) homogenates obtained from the sole of healthy individuals induced a substantial respiratory burst in human neutrophils when assessed by lucigenin-dependent chemiluminescence (CL) in the presence of the fresh human serum. Electron microscopically, the interaction between corneocytes and neutrophils was shown as distinctive deformation of the neutrophils adhering to the surface of the corneocytes that suggested a specific binding between SC and neutrophils. In contrast, in the heat inactivated serum-supplemented system, the peak intensity of SC-induced CL was significantly decreased, being only slightly higher than that noted in the SC free background. To circumvent the time-consuming preparation of the SC homogenates, we measured CL with a sheet of SC obtained by stripping with adhesive cellophane tape. In this case we used plasma because the complement was easily activated by cellophane tape itself when serum was used. To evaluate the influence of the location of horny tissue in the SC on CL in neutrophils, we used SC sheets stripped with cellophane tape from various levels of the SC. However, there was no significant difference in CL responses between SC sheets obtained by 1, 2, 3, 5, 10, or 15 strippings. Our findings suggest that when SC comes in contact with serum, it is opsonized by C3b, and such SC causes a respiratory burst of neutrophils following their specific binding on the surface of corneocytes. PMID- 1937695 TI - Role of interferon-gamma on the in vivo expression of functional interleukin-2 receptors by murine macrophages. AB - Interferon-gamma activates both in vitro and in vivo macrophage functions. Injection of rat recombinant interferon-gamma (rR-IFN-gamma) induced the expression of interleukin-2 receptors (IL-2R) by peritoneal macrophages from normal BALB/c and MRL-+/+ mice. Moreover, rR-IFN-gamma stimulated in a dose dependent manner the oxidative burst of cells as revealed by luminol-dependent chemiluminescene (LDCL). Resident peritoneal macrophages from MRL-lpr/lpr (mice that develop a systemic lupus-like syndrome) showed a higher PMA-triggered LDCL response. This enhanced activity was accompanied by an increase in IL-2R expression (30% vs. less than 1%). The "activated" macrophages from rR-IFN-gamma treated normal mice as well as MRL-lpr/lpr mice did not respond to the addition of recombinant interleukin-2 (rHu-IL-2) by an increase in LDCL. However, rHu-IL-2 triggering became efficient when cells enriched in IL-2R-bearing macrophages were preincubated overnight with rHu-IL-2R. This response may point out a functional role for IL-2R and provide a role for IL-2 in certain macrophage functions. PMID- 1937697 TI - Infections caused by mycobacteria other than tubercle (Mott) bacilli. PMID- 1937698 TI - National tuberculosis programme in India: lacunae in relation to childhood tuberculosis. PMID- 1937699 TI - Mortality patterns in breast versus artificially fed term babies in early infancy: a longitudinal study. AB - The present study comprised 381 term babies weighing greater than 2.5 kg and 126 babies weighing less than or equal to 2.5 kg (low birth weight; LBW) at birth. A longitudinal follow up of 334 babies was done for 6 months. There were 273 'breast fed' babies and 234 'artificially fed' babies. Neonatal mortality rate per 1000 live births for term babies was 37.5, LBW had a rate of 31.5 while those weighing greater than 2.5 kg at birth a rate of 5.9; artificially fed had a mortality rate of 21.6 while breast fed had a low rate of 15.8. For 1-6 months period a mortality rate per 1000 live births of 53.8 was found for term babies, breast fed a rate of 23.9 while artificially fed a rate of 29.9; LBW had a rate of 44.9 while those weighing more than 2.5 kg at birth, a rate of 9. Low birth weight babies whether breast fed or artificially fed had significantly higher mortality than similarly fed babies weighing more than 2.5 kg at birth. Hence, mortality rate for term babies in early infancy can be reduced by simultaneous promotion of breastfeeding and prevention of low birth weight as it was dependent on both variables in this study. PMID- 1937700 TI - Childhood morbidity and mortality in a large hospital over last four decades. AB - Pediatric statistics in a 50-year-old large hospital were analysed to find out any change in pediatric admission rate, morbidity and mortality and outcome of common disorders during the last four decades. Information was collected from four block years from each of the last four decades and compared. An increase of almost 250% in the total pediatric admissions as compared to an increase of 150% in total hospital admissions over last four decades suggest an increased awareness of maternal and child health by the community. The pediatric mortality excluding neonates has not shown a significant fall over the last four decades, being 14.6, 12.7 and 13.0% in 1955-1958, 1974-1977 and 1984-1987, respectively. Diarrheal disorders, pneumonia, tetanus and infections of central nervous system continue to remain the common causes of hospital admissions in children. The morbidity and mortality in these disorders, in general, have shown a significant decline though less appreciable in pyogenic meningitis, encephalitis and tetanus cases. PMID- 1937701 TI - Birthweight: its relationship with maternal and newborn skinfold thickness. AB - Two hundred and forty seven pregnant women at term and their offsprings were studied. Maternal skinfold thickness was measured from ten different sites and newborn skinfold thickness was measured from four different sites in each set of cases. Maternal skinfold thickness was positively correlated with the birthweight and skinfold thickness of the offspring. The birthweight was also positively correlated with the skinfold thickness of offspring. The maternal axillary sites and offspring's subscapular site had higher inter correlation as well as with the birthweight of offspring. PMID- 1937702 TI - A study of relation between physical growth and sexual maturity in girls--V. AB - The findings indicate that sexual maturity would be initiated only after the attainment of requisite morphological body size such as weight on an average nearly 27 kg and height of 137 cm, irrespective of age and SES. The girls from LSES were chronologically older throughout the span of pubertal growth. However, they took lesser time to reach full maturity after the attainment of mid-pubertal growth compared to USES. Menarche appeared after attaining about a minimum weight of 35 kg, height of 143 cm and bicristal breadth is 24 cm. Its appearance followed the attainment of peak height velocity and 3rd developmental stage of breast and/or pubic hair. It, however preceded the attainment of weight and bicristal breadth peak velocities. PMID- 1937703 TI - Deafness in children--an analysis. AB - This study was conducted at the Government Deaf and Dumb School, Thanjavur to ascertain the possible etiological factors. The social outlook of the parents of these children was analysed. Boys were more often affected (60.2%). Consanguinity was observed in 65.4% parents; 23.1% had one or more affected sibling and 14.1% had affected relatives. Parents detected the hearing disability in their children between 3-6 months of age in about 79% cases. Syphilis and chickenpox were the common antenatal associated infections. Streptomycin, chloroquine and abortificients were used during early pregnancy. Eight were preterm and 9 were asphyxiated at birth. A total of 11.5% had purulent ear discharge, and 2 had ear injury. Parents were committed to help the children to be self dependent. PMID- 1937704 TI - Changing trends in intrauterine growth curves. PMID- 1937705 TI - Mothers' perception of congenital heart disease. PMID- 1937706 TI - Spontaneous regression of bilateral retrobulbar masses in a newborn? Neuroblastoma. PMID- 1937707 TI - A translocation between chromosome 1 and 10 in a boy with mental retardation and dysmorphic features. PMID- 1937708 TI - Cerebral gigantism (Sotos syndrome). PMID- 1937709 TI - Tuberculosis meningitis--how early can it occur? PMID- 1937710 TI - Polysplenia syndrome. PMID- 1937712 TI - Fanconi's anemia. PMID- 1937711 TI - Celphos poisoning. PMID- 1937713 TI - Gastric teratoma. PMID- 1937714 TI - Autoimmune hemolytic anemia--mixed type. PMID- 1937715 TI - Febrile seizures. PMID- 1937716 TI - [Guide to purchase of a dental office]. PMID- 1937717 TI - [Three "dental necessities" by Grangeret, "Cutler to the Emperor". 2. Dental instrument. Case of Queen Hortense--myth or reality]. PMID- 1937718 TI - Management of displaced supracondylar fractures of the humerus in children. AB - A series of 33 children with displaced supracondylar fractures of the humerus (SFH) were all treated operatively by open reduction and internal fixation or by closed reduction and percutaneous pinning. A follow-up study was performed on average 29 months (range 3-63 months) after the injury. In 18 per cent of cases primary neurovascular injury was observed and confirmed at operation. Of these patients 32 had open reduction and internal fixation by K-wires; in only one case was closed reduction and percutaneous pinning attempted. If there was preoperative neurological deficit, the nerves were visualized; however nerve suture was not required in our series. In one case we had to reconstruct both the brachial and radial arteries because of intimal lesions totally occluding the vessels. The average hospital stay was 9 days, including pin removal, which was usually performed about 4-5 weeks later, at the time of plaster removal. By Innocenti's criteria, 27 of 30 patients reviewed had an excellent result; three had a good result and three patients were lost to follow-up. There were no complications due to the operation, such as wound healing problems, infections or nerve lesions. In the light of our experience and of the good results, we recommend that displaced SFH be managed by open reduction and internal K-wire fixation. Percutaneous pinning is a good alternative method when closed reduction is successful at the first attempt. PMID- 1937719 TI - Treatment of femoral shaft fractures in children by external fixation. AB - Non-operative management is still the treatment of choice for closed fractures of the femoral shaft in children. Indications for operative intervention would include: children with multiple injuries; severe soft tissue damage; cases where reduction is difficult to maintain; and children not suitable for management by traction. Since 1984, 16 children (mean age 10.3 years) have had stabilization of their femoral shaft fractures by external fixation (Monofixateur) in the Trauma Department of the Hannover Medical School. The external fixation remained in place for a mean of 63 days. Of the 16 children, 15 have been reviewed, with a mean follow-up of 28.2 months. No children who were completely managed with this fixation had any clinically relevant malalignment, but six cases had up to 2 cm difference in leg length. Our observations and experience show that external fixation is a useful alternative for the operative management of femoral shaft fractures in children. It produces good stability, is less invasive, and allows early mobilization. In order to avoid differences in leg length, we recommend a good anatomical reduction with the external fixation being carried out as early as possible. PMID- 1937720 TI - Type III tibial fractures in the elderly: results of 23 fractures in 20 patients. AB - A series of 23 type III fractures of the tibia in 20 elderly patients (over 60 years of age) presenting for combined plastic and orthopaedic surgical management over a period of 15 years are reviewed. Overall limb salvage was 53 per cent, with an average inpatient duration not significantly different from that for amputation, suggesting that an age of over 60 years is not necessarily a contraindication to attempts at limb salvage in type III injuries. PMID- 1937721 TI - Arthrodesis of the shoulder following brachial plexus injury. AB - A series of 13 arthrodeses of the shoulder in adults with brachial plexus injuries have been reviewed. Using internal fixation and external splintage we aimed at a final position of 30 degrees abduction, 30 degrees flexion and 20 degrees of internal rotation. Patients were followed up for between 24 and 60 months. In only one was bony union not achieved, although the resulting fibrous union was asymptomatic. All patients had additional procedures including plexus exploration in six, Steindler procedure in two, triceps to biceps transfer in two, latissimus dorsi transfer in two, and above-elbow amputation in three. All patients stated that shoulder fusion had improved the function of their limb. Minimum range of movement was 50 degrees abduction and 40 degrees flexion. Two patients continued to complain of pain despite solid fusions. Compression arthrodesis of the shoulder is an effective method of achieving fusion and reliably improves the function in adults with brachial plexus injury. PMID- 1937722 TI - The versatility of the free fibula flap in the management of traumatic long bone defects. AB - The free fibula flap has been used to treat ten patients with important long bone defects (mean length 14 cm) following severe trauma. Defects in all the long bones of the limbs have been treated by this technique. Five free osseous and five osteocutaneous flaps were performed. Primary skeletal union occurred at 17 bone junctions (85 per cent) within 5 months. No secondary grafting procedures were required. The mean delay in referral was 17 months and eight patients had already undergone three or more unsuccessful surgical procedures to promote union. The versatility of the vascularized free fibula flap is presented as a one stage reconstruction for large bony and soft tissue defects, stressing the importance of prompt referral and recognition of cases. A combined orthopaedic and plastic surgical approach to these patients is advisable from the onset. PMID- 1937723 TI - MacIntosh-Jones reconstruction for the unstable knee. AB - A group of 45 patients who underwent replacement of a ruptured anterior cruciate ligament with a free graft of one-third of the patellar tendon combined with a lateral extra-articular tenodesis have been reviewed. The average age of the patients was 26.4 years and the mean follow-up period 3.2 years. Stability was achieved in 42 patients (93 per cent), judged on clinical criteria. Overall patient satisfaction was high at 73 per cent and 38 patients (84 per cent) maintained their sporting activity at a social or competitive level. Those who had unsatisfactory results had undergone significant delay before anterior cruciate ligament reconstruction. PMID- 1937724 TI - Incidence and diagnosis of anterior cruciate injuries in the accident and emergency department. AB - A total of 220 consecutive young adults with a traumatic effusion of the knee joint, seen initially in the accident and emergency department, have been reviewed in a weekly orthopaedic acute knee clinic. Of the patients, 80 per cent were seen within 3 days of the injury, and all patients were seen within 8 days of the injury. There were 62 patients (28 per cent) with damage to the anterior cruciate ligament (ACL), of whom 37 patients (17 per cent) had acute complete ACL tears. There were 92 haemarthroses in this series, in which there was a high incidence of ACL damage. The Lachman test was used in this study and identified 73 per cent of the acute complete ACL tears preoperatively and all the chronic ACL injuries. Acute ACL injuries can be diagnose early provided adequate resources are available to provide clinic and theatre facilities. Early diagnosis enables the patients to be given clear advice on future job and sports prospects and allows selection of patients most likely to benefit from augmented repair of the ligament. Associated meniscal lesions can also be identified and treated at an early stage. PMID- 1937725 TI - Assessment of the menisci and cruciate ligaments: an audit of clinical practice. AB - The reliability of clinical assessment of the knee was evaluated in 203 patients using magnetic resonance imaging (MRI). Neither the mechanism of injury nor clinical symptoms were useful indicators of the type of pathology. Physical signs proved insufficiently sensitive in detecting abnormalities. Overall, the accuracy of clinical diagnosis was 80.8 per cent for the anterior cruciate ligament, 62.9 per cent for the medial meniscus and 74.9 per cent for the lateral meniscus. Accurate investigations allow arthroscopy to be targeted to those likely to obtain therapeutic benefit. Reliance upon clinical judgement alone would have resulted in an 89 per cent increase in arthroscopic procedures. Investigations such as MRI or arthrography are concluded to be cost-effective methods of avoiding unnecessary hospitalization, morbidity and waste of limited resources. PMID- 1937726 TI - Injuries caused by animals. AB - Injuries caused by animals and treated at the University Hospital of Umea were analysed. Dogs caused nearly one-half of the injuries, while horses caused one third of the injuries and the highest number of fractures. The 'cost' of treatment and sickness benefit was fairly evenly distributed between horse-, cattle-, and dog-related injuries. The average 'cost' per injured person was, however, highest in those injured in cattle accidents and moose-car collisions. The impact of animal-related injuries on the health care and social security systems was similar to occupational accidents and car accidents in several respects. PMID- 1937727 TI - Traumatic rupture of the diaphragm: a difficult diagnosis. AB - Rupture of the diaphragm occurs in approximately 5 per cent of cases of severe blunt trauma to the trunk, and the mortality may be as high as 50 per cent. The diagnosis is important because of the high incidence of associated organ damage and complications of a missed injury. Successful diagnosis requires a high index of suspicion but can be made from the chest radiograph in 90 per cent of cases if visceral herniation has occurred. We present three cases of rupture of the diaphragm which highlight the frequent occurrence of a delayed or missed diagnosis. PMID- 1937728 TI - Sixty-three cases of traumatic injury of the diaphragm. AB - In the examination of patients with severe thoracic and/or abdominal trauma not requiring surgical exploration, special attention should be given to signs of traumatic diaphragmatic herniation (TDH). We analysed the hospital records of 63 patients with traumatic injuries of the diaphragm. Of these patients, 39 had suffered a blunt trauma in a traffic accident, 21 penetrating trauma, and three had fallen from a great height. There were 51 patients (81 per cent) with left sided diaphragmatic injuries, ten (16 per cent) with right-sided injuries, and in two patients (3 per cent) the injuries to the diaphragm were bilateral. There were 22 patients (35 per cent) who had intrathoracic migration of abdominal viscera. Surgical treatment was given in all cases. Twelve patients (19 per cent) died due to massive haemorrhage, neurological lesions, or septicaemia. Based on the literature and our own experience, we developed a diagnostic protocol for the management of diaphragmatic injuries. Chest radiographs should be made routinely. If diaphragmatic injury is suspected, ultrasound investigation must be performed. If the physician is still in doubt, computed tomography should be performed. At laparotomy, the diaphragm should always be thoroughly examined for lacerations. PMID- 1937729 TI - Blunt liver trauma in children. AB - From 1978 to 1988 228 children under 13 years of age with liver injury following blunt abdominal trauma were studied prospectively. Motor vehicle related accidents were responsible for 85 per cent of the injuries. Isotope liver scan established the diagnosis and identified the pattern of injury. Multiple injuries were seen in 157 patients--predominantly head injuries. The liver was the only intra-abdominal organ injured in 119 patients. There were 69 associated splenic, 33 renal, 21 pancreatic and 3 bowel injuries. There were two deaths (0.88 per cent). Management was non-operative in 215 patients, with resolution of the liver injury in 214. Blood was transfused in 92 patients (40 per cent) (mean volume 20 ml/kg). There were 10 complications; two liver abscesses responded to antibiotics. Follow-up showed complete resolution of the liver injuries. Eight underwent laparotomy because of instability, deterioration or other extrahepatic visceral injuries. All required blood transfusion (mean volume 30 ml/kg). There were eight complications following surgery. PMID- 1937730 TI - Outcome 1 to 3 years after severe traumatic brain injury in children and adolescents. AB - This study reports a consecutive series of 220 children and adolescents who sustained traumatic brain injury (BI) and were admitted to a comprehensive paediatric rehabilitation programme. Progress in areas of mobility, activities of daily living, education and cognitive function were documented for up to 3 years after the injury. Physical recovery was most rapid in the first years and cognitive and language gains generally occurred later, even up to 3 years after the injury. Cognitive assessment at the time of admission proved helpful in predicting outcome; of those patients admitted in a conscious state only one remained dependent for any aspect of self care. Even for those admitted unconscious at a median of 62 days after injury there was good potential for recovery with 27-43 per cent achieving independence in the activities of daily living. For those still unconscious at 6 months, 72 per cent remained vegetative and none achieved the highest cognitive level. Overall, 14 per cent returned to regular education while 25 per cent remained incapable of any educational programme. In a well planned and multidisciplinary rehabilitation programme, patients with severe BI have potential for continued recovery and measurable improvement for at least 3 years. The emphasis should be targeted on differing areas of the therapy programme at different phases of recovery. A realistic appraisal of the ultimate potential for recovery can usually be made by 6 months. PMID- 1937731 TI - Management of duodenal injuries by proximal T-tube drainage. AB - Duodenal injuries may be caused by blunt or penetrating trauma. There is a high mortality rate with this type of injury, particularly when associated with pancreatic trauma. The surgical management of such injuries is difficult and a technique is described which may reduce postoperative morbidity, as illustrated by the two cases described. PMID- 1937732 TI - Comparison of management outcome of primary and secondary referred patients with traumatic extradural haematoma in a neurosurgical unit. AB - A total of 104 patients with a traumatic extradural haematoma in a 5-year period were studied. The mortality of the 71 patients managed primarily by the neurosurgical unit was less than that of the 33 patients secondarily transferred from the district general hospital: 4 per cent vs 24 per cent. This better result was associated with a shorter delay between the time of conscious level deterioration and decompressive operation: 0.7 +/- 1.0 h vs 3.2 +/- 0.5 h. Direct admission of all head injured patients to a neurosurgical unit resulted in significant reduction in mortality and morbidity in patients with an extradural haematoma. PMID- 1937733 TI - Penetrating orbitocranial injury. PMID- 1937734 TI - Corneal perforation due to a fishhook. PMID- 1937735 TI - Overlapping dislocation of pubic symphysis. PMID- 1937736 TI - Spontaneous tibial compartment syndrome. PMID- 1937737 TI - Time of incision in subcutaneous injection of paraffin. PMID- 1937738 TI - The radial recurrent fasciocutaneous flap for coverage of posterior elbow defects. AB - In the last 18 months, we have used the radial recurrent fasciocutaneous flap for the coverage of posterior elbow defects in three patients. The advantages of this one-stage technique are discussed. PMID- 1937739 TI - Traumatic laryngeal fracture. PMID- 1937740 TI - Septic arthritis due to Clostridium welchii. PMID- 1937741 TI - Accidental femoral fracture in infants. PMID- 1937742 TI - An image intensifier laser guidance system for the distal locking of an intramedullary nail. PMID- 1937743 TI - A modified technique for the application of a plaster cast to fresh tibial fractures. PMID- 1937744 TI - Medical teams for accidents and major disasters. PMID- 1937745 TI - Deletion of the BCSP31 gene of Brucella abortus by replacement. AB - The 31-kDa salt-extractable immunogenic protein, BCSP31, was deleted from several Brucella abortus strains by replacement with a marker gene encoding resistance to the antibiotics kanamycin and neomycin. The BCSP31 gene replacement plasmids, constructed with ColE1-derived vectors, were introduced by electroporation into B. abortus strain 19 (S19), into a rough variant of B. abortus S19, and into B. abortus S2308, and antibiotic-resistant transformants were isolated. B. abortus S19 is an attenuated strain used as a vaccine for prevention of bovine brucellosis in the United States, and B. abortus S2308 is a commonly used challenge strain. The antibiotic-resistant isolates were all obtained by recombination; none were spontaneous mutants. Loss of the gene encoding BCSP31 and presence of the marker gene were confirmed by Southern analysis. Vector sequences were either absent or linked to the genome, indicating that ColE1 derived plasmids are not maintained in B. abortus. Survival of B. abortus mutant strains in the macrophagelike cell line J774 and in HeLa cells was examined and shown to be indistinguishable from that of the parental strain. PMID- 1937746 TI - Plasmid and chromosomal elements involved in the pathogenesis of attaching and effacing Escherichia coli. AB - Attaching and effacing (A/E) intestinal lesions are produced by enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and RDEC-1, a pathogen of weanling rabbits. We recently identified a chromosomal locus (eae[E. coli A/E]) which is required for A/E activity in a wild-type EPEC strain. Sequences homologous to those of an eae gene probe were detected in EPEC, RDEC-1, and EHEC isolates. We report here that the eae gene is chromosomally encoded in all EPEC and EHEC strains tested and in RDEC-1. In addition, the eae probe was found to be 100% sensitive and 98% specific in detecting E. coli of EPEC serogroups that demonstrate A/E activity. Ten percent of E. coli of EPEC serogroups that hybridized with the eae probe and produced A/E activity did not hybridize with the EAF (EPEC adherence factor) probe, a plasmid-associated diagnostic probe which is currently used to identify EPEC. In addition to A/E factors, plasmid associated adhesins also contribute to the pathogenesis of EPEC and RDEC-1. To further investigate the role of plasmid-associated adherence, a hybrid RDEC-1 EPEC strain containing the adherence plasmid of an EPEC strain in the A/E background of RDEC-1 was constructed. This hybrid strain, unlike the parent RDEC 1 strain, produced A/E lesions on human tissue culture cells, which suggests that the EPEC adherence plasmid provides tissue specificity to the hybrid strain and that the A/E factors of RDEC-1 are not host restricted. PMID- 1937747 TI - Encapsulation of Cryptococcus neoformans impairs antigen-specific T-cell responses. AB - The encapsulated yeast Cryptococcus neoformans is a significant cause of opportunistic infection in patients with impaired cell-mediated immunity. The major virulence determinant of the organism is an antiphagocytic polysaccharide capsule synthesized after entry into the host. Using both an encapsulated virulent strain and an acapsular avirulent mutant, we have demonstrated the reduced ability of the encapsulated strain to stimulate specific T-cell responses in vitro. This reduction was mediated by the antiphagocytic action of the capsule rather than by direct inhibition of antigen processing and presentation, since prior opsonization with complement enhanced the ingestion of encapsulated yeast cells by purified antigen-presenting cells and allowed significant T-cell activation. Once ingestion had occurred, cryptococci were efficiently processed by activated macrophages via a chloroquine-sensitive pathway. Cryptococcal antigens were available for T-cell recognition within 1 to 2 h of interaction with macrophages and presented in a major histocompatibility complex-restricted manner. Our results suggest that the antiphagocytic action of the polysaccharide capsule is an important determinant for the development of T-cell immunity to C. neoformans. PMID- 1937748 TI - Single-dose tumor necrosis factor protection against endotoxin-induced shock and tissue injury in rats. AB - Tumor necrosis factor (TNF), a macrophage product released in response to endotoxin and other stimuli, has been shown to be a central mediator of endotoxin or septic shock. However, its highly conserved and wide-ranging physiological effects suggest that it may also be an essential cytokine in the host defense against acute bacterial infection or sepsis. A single nontoxic dose of human recombinant TNF administered intravenously 24 h prior to a lethal infusion of Escherichia coli lipopolysaccharide (LPS) completely prevented acute LPS-induced hypotension, ameliorated tissue injury in the lungs and liver, and improved survival in male Fisher 344 rats. The protective effects of TNF were dose dependent and required a 24-h pretreatment interval. After the infusion of LPS, animals in both groups (TNF-treated animals and saline-pretreated controls) initially appeared acutely ill and had a similar severe metabolic acidosis, indicating that TNF did not inactivate or prevent the toxic effects of LPS. Twelve hours after the administration of TNF, the gene for manganous superoxide dismutase, a mitochondrial enzyme which scavenges toxic reactive oxygen species and is induced during conditions which generate a free radical stress, was expressed in liver tissue, suggesting that the induction of manganous superoxide dismutase may be an important in vivo protective mechanism against cellular injury during lethal endotoxemia. PMID- 1937749 TI - Intramacrophagic Mycobacterium avium bacilli are coated by a multiple lamellar structure: freeze fracture analysis of infected mouse liver. AB - We used freeze fracture electron microscopy to study the fine structure of Mycobacterium avium inside phagosomes of murine macrophages. M. avium-susceptible C57BL/6 mice were infected with M. avium by intraperitoneal inoculation of 10(8) viable bacilli. We studied the microanatomy of the mycobacteria in 3-month infections of mice, a situation in which bacillary multiplication is extensive. In these samples, freeze fracture revealed that intraphagosomal bacilli were surrounded by a multilamellar coat that was apposed to the cell wall. In thin sections, in contrast, the area corresponding to the coat showed no substructure and was electron transparent (the so-called electron-transparent zone that has been previously reported by others). The multiple lamellae resembled an onionlike assembly that was inserted in between the mycobacterial wall outer surface and the phagosomal membrane. Each lamella of the M. avium coat was made up of parallel straight fibrils with a width of 5 nm. A variable number of lamellae, sometimes up to 10 or more elements, coated individual bacilli. The multilamellar coat was absent around both extracellular M. avium and intramacrophagic M. avium after short-term (45-min) inoculation of mice. The supramolecular organization of the M. avium lamellar coat as viewed here by freeze fracture is similar to that of purified mycoside C (P. Draper, J. Gen. Microbiol. 83:431-433, 1974; K.-S. Kim, M.R.J. Salton, and L. Barksdale, J. Bacteriol. 125:739-743, 1976), a mycobacterial component currently known as glycopeptidolipid (W.W. Barrow and P.J. Brennan, J. Bacteriol. 150:381-384, 1982). We conclude that M. avium bacilli growing in macrophages are surrounded by multilamellar capsulelike structures that contain glycopeptidolipid molecules. PMID- 1937750 TI - Antibody recognition and isoelectrofocusing of antigens of the malaria parasite Plasmodium yoelii. AB - Inbred BALB/c mice were either immunized with Triton X-100-extracted antigens of blood-stage Plasmodium yoelii or infected with P. yoelii and cured in three successive schedules. Whereas the immunized BALB/c became only partially protected from subsequent challenge infection with blood-stage P. yoelii, the convalescent mice acquired total immunity. When total P. yoelii antigen extract was resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose, and immunoblotted with anti-P. yoelii serum, five major protein bands of 150, 84, 40, 19, and 16 kDa were recognized by the sera of fully protected convalescent mice but not by the sera of partially protected mice. The utility of comparing reactivities of sera from fully protected and partially protected malaria hosts and the possibility that antigens uniquely recognized by the convalescent mouse sera may contribute to immunity against P. yoelii infection are discussed. Although previously reported to be an effective adjuvant for immunization against P. yoelii infection in (BALB/c x C57BL)F1 hybrid mice, saponin did not promote protection any better than did Freund adjuvant in BALB/c mice immunized with detergent-extracted P. yoelii antigen. Most of the P. yoelii proteins (14 to 250 kDa) found in Triton X-100 extracts of P. yoelii-parasitized erythrocytes isoelectrofocused as a single peak in the pH region 4.4 to 4.6, suggesting a rationale for previous findings that the most anti-P. yoelii protective and T-helper activities are induced by antigens isoelectrically focused in a fraction of similar pH. PMID- 1937751 TI - DNA sequence and in vitro mutagenesis of the gene encoding the fructose-1,6 diphosphate-dependent L-(+)-lactate dehydrogenase of Streptococcus mutans. AB - Previously, the fructose-1,6-diphosphate-dependent L-(+)-lactate dehydrogenase gene of Streptococcus mutans JH1000 was cloned into Escherichia coli (J. D. Hillman, M. J. Duncan, and K. P. Stashenko, Infect. Immun. 58:1290-1295, 1990). In the present study, the nucleotide sequence of 1.29 kb of S. mutans DNA which contained the promoter and protein-coding region of the gene was determined. In vitro disruption of the gene was achieved by deletion of the promoter and a major portion of the protein-coding sequence. Subsequently, a tetracycline resistance gene from S. mutans was inserted at the deletion site as a marker for selection. In addition, evidence from Southern hybridization showed that S. mutans JH1000 contained a single copy of the lactate dehydrogenase gene. PMID- 1937753 TI - Listeria monocytogenes isolates can be classified into two major types according to the sequence of the listeriolysin gene. AB - The nucleotide sequence of a 3.5-kb BamHI fragment from Listeria monocytogenes 12067, a human clinical isolate of serotype 4b, has been determined. The DNA fragment harbors the gene for listeriolysin, part of the gene for a phosphatidylinositol-specific phospholipase C, and part of the gene for a metalloprotease. Comparison of the sequence with corresponding sequences from two other L. monocytogenes isolates revealed a significant number of nucleotide differences. Several of the differences give rise to amino acid substitutions. The most variable region was the examined part of the mpl gene, whereas the lisA gene showed a relatively high degree of conservation, particularly at the amino acid level. To analyze the pattern of sequence variability in the lisA gene, a 160-bp region covering nine nucleotide differences was sequenced from 36 isolates of different origins. This work showed that the strains can be grouped into two major types according to the nucleotide sequences. Oligonucleotide probing of a larger number of L. monocytogenes isolates showed that the observed differences can be used to subdivide the species. The data suggest a correspondence between the sequence type of the lisA gene and flagellar antigens. Assays based on hybridization or the polymerase chain reaction with type-specific oligonucleotides may provide fast and easy alternative methods for strain typing. PMID- 1937752 TI - Role of inorganic nitrogen oxides and tumor necrosis factor alpha in killing Leishmania donovani amastigotes in gamma interferon-lipopolysaccharide-activated macrophages from Lshs and Lshr congenic mouse strains. AB - The capacity of mature bone-marrow-derived macrophages and resident peritoneal macrophages from Lshr versus Lshs congenic mice to kill intracellular Leishmania donovani amastigotes when activated by recombinant gamma interferon lipopolysaccharide (rIFN-gamma-LPS) was examined. IFN-gamma alone in doses up to 100 U/ml was unable to activate macrophages to kill L. donovani amastigotes in vitro; LPS was a necessary secondary stimulus. Similarly, LPS alone in doses up to 100 ng/ml produced no leishmanicidal activity. In bone marrow macrophages, a dose-dependent increase in leishmanicidal activity was observed as increasing rIFN-gamma-LPS dose combinations were introduced, with Lshr macrophages maintaining a significant but not dramatic advantage within any particular dose combination. For peritoneal macrophages, the reverse was true, with macrophages from Lshs mice being more efficient at killing for doses of LPS up to 10 ng/ml with doses of rIFN-gamma in the range of 11 to 33 U/ml. The degree of killing in both bone marrow and peritoneal macrophages correlated well with the levels of nitrites measured in the supernatants at 72 h, and a highly significant correlation was observed between 4-, 24-, or 72-h tumor necrosis factor alpha (TNF-alpha) release and nitrite production measured at 72 h. Inclusion of 200 microM NG-monomethyl-L-arginine, a competitive inhibitor of the L-arginine dependent pathway for the synthesis of inorganic nitrogen oxides, inhibited the killing, as did the addition of neutralizing anti-TNF-alpha antibody. These results are consistent with previous data showing an important autocrine role for TNF-alpha in enhancing production of inorganic nitrogen oxides by primed or activated macrophages. In addition, our results suggest that production of TNF alpha and nitrites after priming or activation signals may be under a different regulatory control in mature bone marrow macrophages than in the resident peritoneal macrophage population. PMID- 1937754 TI - Involvement of interleukin-1 (IL-1), IL-6, IL-2, and IL-4 in generation of cytolytic T cells from thymocytes stimulated by a Mycoplasma fermentans-derived product. AB - The capacity of Mycoplasma fermentans-derived high-molecular-weight material (MDHM) to generate cytolytic T cells from mitogen-stimulated murine thymocytes was studied in detail. The role of MDHM and the involvement of monokines and lymphokines resulting from the addition of MDHM to thymocyte cultures were examined in complete and adherent cell-depleted culture systems by the addition of neutralizing monoclonal antibodies against interleukin-2 (IL-2), IL-4, and IL 6 and in reconstitution experiments with recombinant mediators. The data presented here suggest that MDHM is crucial only in the first phase of a reaction sequence beginning with the stimulation of adherent accessory cells and resulting in the synthesis of IL-1 and IL-6. The lymphokines IL-2 and, primarily, IL-4 are required in a second step which, once these lymphokines are formed, can proceed in the absence of MDHM and accessory cells and leads to the formation of cytolytic T cells. The elucidation of the MDHM-induced reaction sequence may be of relevance in view of the hypothetical role of mycoplasmas in rheumatic disease in humans. M. fermentans is an organism capable of infecting humans and in an early report has been discussed as a causative agent for rheumatoid arthritis. PMID- 1937756 TI - Antibodies and DNA probes used to analyze variant populations of the Indochina-1 strain of Plasmodium falciparum. AB - Ten variant populations derived from the Indochina-1 strain of Plasmodium falciparum were analyzed by using (i) hyperimmune serum raised against some of these populations in squirrel monkeys and (ii) an oligonucleotide probe based on the rep-20 sequence, which had previously been shown to be a useful marker of diversity. Although all 10 subpopulations had an identical fingerprint pattern on Southern blots probed with the oligonucleotide, thus demonstrating a homogeneous genetic makeup, they all had a different phenotype for erythrocyte-associated antigens, thus confirming serological variant-specific differences. Antibodies to erythrocyte-associated antigens were measured with a new technique including immunogold and silver enhancement. The results of this study indicate that antigenic variation can occur without major genomic reorganization. PMID- 1937755 TI - MDHM, a macrophage-stimulatory product of Mycoplasma fermentans, leads to in vitro interleukin-1 (IL-1), IL-6, tumor necrosis factor, and prostaglandin production and is pyrogenic in rabbits. AB - Mycoplasma fermentans-derived high-molecular-weight material (MDHM) was originally discovered because of its capacity to generate, through the induction of monokine synthesis, cytolytic T lymphocytes in concanavalin A-stimulated thymocyte cultures. This study shows that MDHM-activated macrophages not only released interleukin-6 (IL-6) but also exhibited increased synthesis of cell associated IL-1 as well as liberation of tumor necrosis factor and prostaglandin. We determined 6-keto prostaglandin F1 alpha since it is the stable metabolite of the bioactive prostacyclin. MDHM appeared to be as potent as lipopolysaccharide in inducing the synthesis of these mediators. Priming with gamma interferon further increased MDHM-mediated IL-6 release. Since monokines can be pyrogenic, we tested the effects of an intravenous injection of MDHM on rectal temperatures and leukocyte counts in rabbits. At 1 h after a bolus injection of MDHM, leukocyte counts dropped to about 35% of the initial values, reflecting a decrease in both lymphocytes and granulocytes. At 4 to 6 h after injection, granulocyte counts began to increase again, whereas lymphocyte counts remained low. No leukocytosis was noted during this time. The lack of leukocytosis can be explained by the failure of MDHM-stimulated macrophages to release IL-1. The property of MDHM to cause IL-6 release from macrophages and the IL-6 growth dependency of the 7TD1 hybridoma cell line were made use of in a coculture assay system to quantitate the activity of MDHM. With this method and macrophages from C3H/HeJ lipopolysaccharide-nonresponder mice, MDHM activity was found to be equally distributed in the mycoplasma growth medium and the sedimented mycoplasmas after sonication. PMID- 1937757 TI - Identification and purification of transferrin- and lactoferrin-binding proteins of Bordetella pertussis and Bordetella bronchiseptica. AB - Bordetella pertussis and Bordetella bronchiseptica were both able to grow in iron deficient medium when supplemented with iron-saturated human lactoferrin or transferrin but not with human apotransferrin. Direct contact between the transferrins and the Bordetella cells did not appear to be required for growth but considerably improved the growth of the organisms. Analysis of B. pertussis and B. bronchiseptica whole-cell lysates from cultures carried out in iron deficient or iron-replete media revealed iron-repressible proteins (IRPs) of 27 kDa in B. pertussis and of 30, 32, 73.5, and 79.5 kDa in B. bronchiseptica. Iron inducible proteins of 16, 23.5, 36.5, and 92.5 kDa and of 17, 23.5, 70, 84, and 91 kDa were also identified in B. pertussis and B. bronchiseptica, respectively. By use of affinity chromatography with iron-saturated human lactoferrin or transferrin as ligands, the 27- and 32-kDa IRPs from B. pertussis and B. bronchiseptica, respectively, were specifically isolated. By using iron-chelated affinity columns, we showed that these proteins exhibit an affinity for iron. Cell fractionation experiments indicated that both of these proteins are probably associated with the outer membrane. Growth of the organisms under modulating conditions showed that the production of these IRPs is not under the genetic transcriptional control of vir or bvg, the general virulence regulon in Bordetella spp. PMID- 1937758 TI - Variant surface antigens of Giardia lamblia are associated with the presence of a thick cell coat: thin section and label fracture immunocytochemistry survey. AB - Giardia lamblia undergoes surface antigenic variation. The ultrastructural location of antigens on four different variants was studied by label fracture and immunocytochemistry with four monoclonal antibodies (MAbs), each of which recognized the predominant variant in a particular clone. Each Giardia clone and its reacting MAb showed similar findings. The entire surface of the organism was covered by a surface coat which contained the variant surface protein. The surface coat was densely and uniformly labeled. Unreacting MAbs failed to label the surface. Label-fractured Giardia trophozoites exposed to reactive MAb revealed a planar distribution of reactivity with no discernible relationship to visualized intramembranous particles. Unexpectedly, some Giardia trophozoites lacked a surface coat and consequently failed to react with the appropriate MAb. The biological relevance of coatless Giardia trophozoites is unknown. These findings localize the variant antigens to the surface coat of the parasite and identify a minority of the population which lacks a surface coat. PMID- 1937760 TI - Accumulation of plasma cells in inflamed sites: effects of antigen, nonspecific microbial activators, and chronic inflammation. AB - Plasma cells are common in chronically inflamed sites, including periodontal lesions. The aim of this study was to determine which factors contribute to this local accumulation of plasma cells. Specifically, we sought to evaluate the effects of specific antigen and nonspecific activators from an infectious agent associated with chronic inflammation (Fusobacterium nucleatum, an organism prominent in chronic periodontal lesions) and the effect of the chronic inflammation itself. Chronic inflammation (14 to 17 days) was induced in horseradish peroxidase (HRP)-immune rabbits by subcutaneous injection of 50 microliters of sterile alum in several sites in their backs. Controls included sites injected with saline or more acute sites examined after 3 days of alum inflammation. Sites were challenged with HRP (the antigen), sonicated F. nucleatum (the nonspecific activator), or both together to see whether F. nucleatum has an adjuvant effect. Three days after challenge, HRP-specific antibody-forming cells (AFC) were enumerated after peroxidase histochemistry. In noninflamed sites or sites with acute inflammation, virtually no HRP-specific AFC were evident. In contrast, chronic inflammation alone was sufficient to elicit a specific AFC response (congruent to 10 cells per mm2). Addition of either F. nucleatum or HRP to the chronic lesion about doubled the number of HRP-specific AFC. However, a dramatic 8- to 15-fold (80 to 150/mm2) increase was seen in chronically inflamed sites challenged with antigen and activator together. Interestingly, the activator did not have this adjuvant effect in the acute sites or in normal skin. In short, accumulation of plasma cells in inflamed sites is promoted by chronic inflammation, activators of microbial origin, and specific antigen. This milieu can be expected to develop in some periodontal lesions and could help explain why gingival crevicular fluid from some sites may contain extraordinary levels of locally produced specific antibodies for certain antigens. PMID- 1937759 TI - Recombinant Escherichia coli clones expressing Chlamydia trachomatis gene products attach to human endometrial epithelial cells. AB - To identify Chlamydia trachomatis genes involved in attachment to host cells, a chlamydial genomic library was screened on the basis of binding characteristics by two methods. In the whole-cell screen, individual recombinant Escherichia coli clones were assayed for adherence to eukaryotic cells. In the membrane-binding screen, each recombinant colony of E. coli was treated with CHCl3 and assayed for binding to purified, 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate (CHAPS)-solubilized, 35S-labeled eukaryotic membrane material. Initial screening with McCoy cells was refined by using HEC-1B cells, a human endometrial epithelial cell line, which discriminate among recombinants adhering to McCoy cells. Some recombinants demonstrate significantly greater adherence to HEC-1B cells than to McCoy cells and appear, by transmission electron microscopy, to associate with electron-dense areas of the epithelial cell plasma membrane, resembling coated pits. Recombinants positive by one or both screening methods were examined by Southern and Western (immunoblot) analyses, which revealed the presence of chlamydial sequences inserted in the plasmids and the expression of novel 18-, 28-, and approximately 82 kDa, and perhaps of 18 Maxicell analysis of selected recombinants confirmed that the proteins of 28 and approximately 82 kDa, and perhaps of 18 kDa, are plasmid encoded. Antiserum generated against the recombinant approximately 82-kDa protein reacted in Western analysis with a similar-sized protein from C. trachomatis serovar E elementary bodies (EB) and reticulate bodies, serovar L2 EB, and C. psittaci EB. E. coli JM109(pPBW58) contains a 6.7-kb plasmid insert which encodes proteins of all three sizes. Under a number of different conditions in the whole-cell attachment assay--i.e., at 4 degrees C, in Ca(2+)- and Mg(2+)-free medium, in the presence of trypsin or dextran sulfate, and with rabbit aortic endothelial cells--the binding specificity of JM109(pPBW58) parallels that of C. trachomatis EB. Finally, the adherence phenotype of E. coli JM109(pPBW58) correlates directly with the presence of the recombinant plasmid; the phenotype is lost concurrently with loss of the recombinant plasmid, and the into E. coli JM109. The role of the 18-, 28-, and approximately 82-kDa proteins in mediating attachment, whether they act in concert as a complex or individually, has yet to be determined. PMID- 1937762 TI - Subgingival microbiota in squirrel monkeys with naturally occurring periodontal diseases. AB - The squirrel monkey (Saimiri sciureus) has been proposed as an in vivo model for the study of subgingival colonization by suspected periodontopathogens, such as black-pigmented porphyromonads and prevotellas (BP/P). However, the indigenous microbiota of the squirrel monkey has not been well described. Therefore, in order to more fully characterize the oral microbiota of these animals, we studied two groups of squirrel monkeys from widely different sources. Group I consisted of 50 breeding colony monkeys ranging in age from 9 months to over 6 years which had been raised in captivity; group II consisted of 16 young sexually mature monkeys recently captured in the wild in Guyana. Group I animals in captivity had developed moderate to severe gingivitis, with a mean gingival index (GI) of 2.6; 52% of the sites bled, 26% had detectable calculus, and 83% had detectable BP/P. A group I subset (six animals), for which predominant cultivable microbiota was described, had a mean GI of 2.4. Colony morphology enumeration revealed that five of the six subset animals were detectably colonized with BP/P (range, 0 to 16.9%) and Actinobacillus actinomycetemcomitans (range, 0 to 3.9%); all subset animals were colonized with Fusobacterium species (range, 0.8 to 3.6%), Actinomyces species (range, 2.3 to 11%), and gram-positive cocci (range, 1.4 to 21.4%). Predominant cultivable microbiota results revealed the presence of many bacterial species commonly found in the human gingival sulcus. At baseline, group II animals were clinically healthy and had a mean GI of 1.4; 67% of the sites bled and 2.1% had calculus, and none of the animals had detectable BP/P. Neisseriae were very common in noninflamed sites. Subsequently, when inflamed sites were compared with noninflamed sites in group II animals after they had been maintained in captivity for 6 months, inflamed sites exhibited a more complex microbiota and increased proportions of gram-negative rods and asaccharolytic bacteria. PMID- 1937761 TI - Isolation and characterization of Bordetella avium phase variants. AB - Two spontaneous phase variants of Bordetella avium were isolated at a frequency of 2 x 10(-4) by colony immunoblot assay of B. avium with antibody against B. avium dermonecrotic toxin. The two phase variants, designated GOBL309 and GOBL312, lack dermonecrotic toxin and four outer membrane proteins with molecular masses of 93, 48, 38, and 27 kDa but retain the ability to agglutinate guinea pig erythrocytes. The proteins which are not expressed by GOBL309 and GOBL312 correspond to five proteins which are phenotypically modulated in B. avium by growth in the presence of nicotinic acid or MgSO4. Growth of the phase variants in supplemented Stainer-Scholte media containing nicotinamide did not alter expression of these five proteins. Intranasal inoculation of the spontaneous phase variants into 3-day-old turkeys and reisolation of B. avium at 2 weeks postinoculation resulted in the recovery of B. avium which had the wild-type phenotype, colonized the turkey tracheas, and produced the four outer membrane proteins and dermonecrotic toxin. Hybridization of B. avium and B. avium-like chromosomal DNA with internal portions of the Bordetella pertussis virulence regulatory genes, bvgA and bvgS, revealed that B. avium and B. avium-like isolates contain 5.3- and 5.7-kb DNA fragments, respectively, which are homologous to bvgS. B. avium and B. avium-like chromosomal DNA failed to hybridize to B. pertussis bvgA. PMID- 1937763 TI - X-irradiation of Eimeria tenella oocysts provides direct evidence that sporozoite invasion and early schizont development induce a protective immune response(s). AB - Sporulated oocysts of the protozoan parasite Eimeria tenella were attenuated by exposure to various doses of X-radiation to inhibit intracellular replication and thus determine whether sporozoites alone can induce a protective immune response. Exposure to doses greater than 15-kilorads had a significant effect on development, as indicated by the absence of oocyst production in chickens infected with parasites treated with 20 or 30 kilorads of radiation. Infection with nonirradiated or 15-kilorad-exposed parasites led to either normal or reduced oocyst shedding. Equivalent protection was afforded chickens inoculated with a minimum immunizing dose of either nonirradiated or 20-kilorad-irradiated E. tenella oocysts. Immunofluorescence staining of cecal tissue from chickens inoculated with 10(7) nonirradiated or 20- or 30-kilorad-irradiated oocysts with stage-specific monoclonal antibodies showed no significant difference in sporozoite invasion between treatment groups. Normal merogonic development was observed at appropriate times (48, 60, 72, and 96 h) postinfection in chickens inoculated with nonirradiated oocysts. In contrast, irradiated parasites exhibited minimal merogonic development at 48 h postinfection. Furthermore, no merogonic stages were observed at times of otherwise peak merozoite development (60, 72, and 96 h) in cecal tissue from chickens inoculated with irradiated parasites. Infection of chicken cells with irradiated or nonirradiated parasites in vitro corroborated these findings and indicate that events early after sporozoite invasion induce a protective immune response against this parasite. PMID- 1937765 TI - Association between a large plasmid and 15- to 17-kilodalton antigens in virulent Rhodococcus equi. AB - Rhodococcus equi strains showing 15- to 17-kDa antigens in immunoblots were found to be virulent in mice. To study the genes specific to these antigens in virulent R. equi, we compared plasmid profiles, immunoblot profiles, and murine pathogenicity profiles of 10 strains of R. equi. All the strains showing 15- to 17-kDa antigens contained a large plasmid of approximately 85 kbp and were virulent in mice; however, the remaining strains lacked both the antigens and the large plasmid and were avirulent in mice. Mutants of virulent strains ATCC 33701 and L1, which were cured of the large plasmid by repeated passage at 38 degrees C, lacked the 15- to 17-kDa antigens and showed a dramatic decrease in lethality in mice. These results suggested that the presence of an 85-kbp plasmid may be essential for virulence and expression of 15- to 17-kDa antigens of R. equi and offered support for earlier observations that freshly isolated strains of R. equi killed mice, whereas laboratory-adapted strains did not. PMID- 1937764 TI - Murine macrophage activation by staphylococcal exotoxins. AB - We investigated the ability of staphylococcal enterotoxins A and B, exfoliative toxins A and B, and toxic shock syndrome toxin 1 to activate macrophages. All of the toxins tested had the potential to stimulate tumoricidal activity in peritoneal macrophages from lipopolysaccharide-responsive C3HeB/FeJ mice. In contrast, none of the toxins activated cytotoxicity in lipopolysaccharide unresponsive macrophages from C3H/HeJ mice. We also studied toxin stimulation of monokine secretion. Staphylococcal enterotoxin A, toxic shock syndrome toxin 1, and both exfoliative toxins triggered C3HeB/FeJ macrophages to secrete tumor necrosis factor alpha, but enterotoxin B induced only marginal amounts of tumor necrosis factor. All of the toxins used stimulated interleukin-6 production by macrophages from both strains of mice. Nitric oxide is produced in response to the exfoliative toxins only by the lipopolysaccharide-responsive macrophages. These results suggest that macrophages respond differently to several staphylococcal exotoxins. PMID- 1937766 TI - Distribution, persistence, and recall of serum and salivary antibody responses to peroral immunization with protein antigen I/II of Streptococcus mutans coupled to the cholera toxin B subunit. AB - After peroral immunization of mice with surface protein antigen (Ag) I/II of Streptococcus mutans conjugated to the cholera toxin B (CTB) subunit, cells actively secreting immunoglobulin A (IgA) antibodies specific for Ag I/II, but not for CT, were induced in the salivary glands; salivary IgA anti-Ag I/II antibodies and total salivary IgA were also elevated. The development of large numbers of IgA and IgG antibody-secreting cells in the mesenteric lymph nodes and spleen and high levels of serum IgA and IgG antibodies to Ag I/II and CT demonstrated that a response to both antigens occurred. At least two to three intragastric doses of 15 micrograms or more of Ag I/II-CTB conjugate, plus free CT as an adjuvant, were needed to induce the salivary IgA anti-Ag I/II response, which peaked at about 35 days and persisted at lower levels for 5 to 6 months. A single booster intragastric immunization did not induce enhanced salivary IgA anti-Ag I/II antibodies relative to the primary response, but serum IgA and IgG antibodies to both Ag I/II and CT showed evidence of marked anamnestic responses. The results indicated that relatively long-term mucosal IgA antibody responses could be induced by peroral immunization with small quantities of a CTB conjugated protein. However, additional factors governed the distribution of cells secreting antibodies of different specificities, or capable of mounting anamnestic responses, between different compartments of the mucosal and circulatory immune systems. PMID- 1937768 TI - Sex differences in host resistance to Mycobacterium marinum infection in mice. AB - Sex differences were observed in host resistance to Mycobacterium marinum infection in mice. Males were found to be more susceptible than females in terms of mortality, incidence of gross skin lesions, and bacterial load in the lungs and spleen. The degree of sex differences varied from strain to strain of test mice, in the order C3H/He, A/J, and BALB/c greater than DBA/2, B10.A, and C57BL/6, on the basis of survival time and multiplication of organisms in the visceral organs. Although this ordering corresponded to the susceptibilities of both male and female mice to the organisms, much greater strain dependency was seen in males than in females. Castration caused an increase in the host resistance of males, but this effect was substantially reversed by continuous testosterone treatment. Testosterone also increased the susceptibility of female mice to this infection. These findings imply that the male sex hormone is involved in the lowered anti-M. marinum resistance of males. Although athymic mice were more susceptible than euthymic mice, a substantial degree of sex difference was also observed in the T-cell-depleted animals, indicating that natural host resistance to this infection is sex dependent. Indeed, more efficient macrophage mobilization at the site of infection was seen in females than in males. Although female T-cell transplantation improved the lowered resistance of athymic mice, there was a sex difference in bacterial growth in the lungs. This implies that sex hormones affect T-cell functions. PMID- 1937767 TI - Small-animal model to measure efficacy and immunogenicity of Shigella vaccine strains. AB - The development of a small-animal model to test the protective efficacy and immunogenicity of a vaccine strain against shigellosis would greatly facilitate the evaluation of potential vaccine candidates. In guinea pigs, the ability of shigellae to invade and multiply within the corneal epithelium, causing keratoconjunctivitis, closely mimics the invasion process in the intestinal epithelium (B. Sereny, Acta Microbiol. Acad. Sci. Hung. 4:367-376, 1957). The serum response of animals recovering from a Shigella keratoconjunctival infection was determined and found to be consistent with that shown by convalescent humans and primates. This model was used to test the efficacy of two vaccine candidates, and the immune response of the guinea pigs to the vaccine strains was examined. Both vaccine strains demonstrated significant protection against challenge by homologous virulent Shigella strains, and the results were comparable with results obtained in trials with monkeys. The guinea pig model also provides a rapid and inexpensive means of evaluating different immunization regimens as well as of testing other variables such as length of protection against disease. PMID- 1937769 TI - Adherence of oral "Streptococcus milleri" cells to surfaces in broth cultures. AB - Cells of representative strains of oral "Streptococcus milleri" firmly adhered to glass surfaces when grown in glucose broths as well as in fructose and sucrose broths. Cellular adherence occurred on saliva-coated glass surfaces as well as uncoated surfaces, but the cells of only a few (6 of 69) tested adherent strains agglutinated upon the addition of human whole-saliva supernatant. Thus, the firm adherence of growing "S. milleri" cells is independent of sucrose and salivary macromolecules. Two macroscopic forms of cell adherence were observed: one was a coarse-granule type and one was a tiny-granule type covered with a thin homogeneous membranous material. Scanning electron microscopy revealed that, in both types, a stringy substance interconnected the cells and connected the cells to glass surfaces, with amorphous flocklike materials present in the intercellular space. Of the 154 tested strains, 128 were adherent, of which 90 were firmly and extensively (+2 or +3) adherent. Most strains of the serovars f/F, g, h, i, j, g-, and gj- were extensively adherent. Generally, cells of the more strongly adherent strains were more hydrophobic and spontaneously aggregating. However, there also existed a few hydrophilic and nonaggregating but extensively adherent strains. The presence of trypsin or pronase completely inhibited the adherence of some strains (mostly nonaggregating) but did not at all inhibit that of others (mostly aggregating). The adhering groups did not significantly differ in their cell surface hydrophobicities. Therefore, at least two factors, one proteinaceous and one nonproteinaceous, appear to be principally involved in the firm surface adherence of "S. milleri." PMID- 1937770 TI - Isolation and molecular characterization of spontaneously occurring cytolysin negative mutants of Actinobacillus pleuropneumoniae serotype 7. AB - Actinobacillus pleuropneumoniae serotype 7 strains are shown to spontaneously lose cytolytic activity with a frequency of approximately 10(-4). The phenotypic change is associated with the loss of approximately 8.5 kbp of chromosomal DNA. A genomic fragment encoding the cytolysin and its flanking sequences was cloned and characterized. Also, the corresponding truncated fragment was cloned from a spontaneous mutant. Comparison of the two clones allowed the definition of the excision site. The ends of the excised fragment are composed of 1,201 bp long direct identical repeats, possibly facilitating the genotypic change by homologous recombination. In accordance with this hypothesis, one repeat is conserved in the spontaneous mutant. Each repeat contains one open reading frame preceded by a Shine-Dalgarno consensus sequence, and the ends of each repeat contain 26-bp complementary sequences with four mismatches. PMID- 1937771 TI - Susceptibility of Rickettsia tsutsugamushi Gilliam to gamma interferon in cultured mouse cells. AB - Recombinant rodent gamma interferon (IFN-gamma) inhibited the infection of cultured BALB/3T3 mouse fibroblasts by Rickettsia tsutsugamushi Gilliam, apparently mainly by clearance of intracellular rickettsiae. No significant effect on rickettsial entry into the cells was noted; IFN-gamma was toxic to infected cells, as measured by the capacity of treated, infected cells to attach to the surfaces of culture vessels. In a small proportion of IFN-gamma-treated cells, rickettsial replication appeared to persist at normal levels. A fraction (28%) of rickettsiae clonally isolated from cultures treated with IFN-gamma was resistant to IFN-gamma-mediated inhibition, but four serial passages of these resistant clones in the absence of additional IFN-gamma resulted in the loss of resistance. In several respects, therefore, the IFN-gamma-mediated inhibition of scrub typhus rickettsiae in cultured fibroblasts was similar to that reported for Rickettsia prowazekii. PMID- 1937772 TI - A new in vitro model of Entamoeba histolytica adhesion, using the human colon carcinoma cell line Caco-2: scanning electron microscopic study. AB - The human colon carcinoma cell line Caco-2, which is widely used to study the adhesion and cytotoxicity of enterobacteria, was used to investigate the adhesion of the trophozoites of Entamoeba histolytica. We observed a high percentage of adhesion of amoebae to Caco-2 cells. Scanning electron microscopy showed that amoebial membrane structures were involved in adhesion and the cytolytic action. These differentiated cells should prove to be a useful model system for investigation of the pathogenic action of amoebae. PMID- 1937773 TI - Extracellular release of reactive oxygen species from human neutrophils upon interaction with Escherichia coli strains causing renal scarring. AB - The production of reactive oxygen metabolites by neutrophils plays a key role in the host defense against invading microorganisms and in tissue damage resulting from infection. In the present study we measured the ability of different uropathogenic Escherichia coli strains to induce generation of oxygen metabolites upon interaction with human neutrophils. The strains were selected to represent two groups of patients with recurrent episodes of acute pyelonephritis: one with renal scars (12 strains) and one without renal scarring (11 strains). The majority of strains (from both groups) induced a pronounced neutrophil respiratory burst activity. When the intracellular and extracellular oxidative responses were measured separately, it was found that the response induced by nonscarring strains was primarily of intracellular (intraphagosomal) origin, whereas a proportionally larger fraction of the response induced by the scarring strains was extracellular. Since reactive oxygen products are toxic to the renal tissue, this release can be of importance in the development of renal scars. PMID- 1937774 TI - Shiga toxin-associated hemolytic-uremic syndrome: combined cytotoxic effects of Shiga toxin, interleukin-1 beta, and tumor necrosis factor alpha on human vascular endothelial cells in vitro. AB - This study explores the relationship between Shiga toxin-producing Shigella or Escherichia coli strains and the development of vascular complications in humans following bacillary dysentery. We propose that endotoxin-elicited interleukin-1 or tumor necrosis factor alpha (TNF) may combine with Shiga toxin to facilitate vascular damage characteristic of hemolytic-uremic syndrome. This study examines the cytotoxic effects of Shiga toxin, interleukin-1, and TNF on cultured human umbilical vein endothelial cells (HUVEC). Both Shiga toxin and TNF were cytotoxic to HUVEC, although HUVEC obtained from individual umbilical cords differed in their sensitivities to these agents. With Shiga toxin-sensitive HUVEC, combinations of TNF with Shiga toxin resulted in a synergistic cytotoxic effect. In contrast, interleukin-1 was not cytotoxic to HUVEC, nor did it enhance cell death in combination with Shiga toxin. The synergistic cytotoxic response of HUVEC to Shiga toxin and TNF was dose and time dependent for both agents and could be neutralized by monoclonal antibodies directed against either Shiga toxin or TNF. This synergistic response was delayed, being maximal on day 2. Preincubation (24 h) of HUVEC with TNF sensitized the cells to Shiga toxin. TNF alone had no effect on HUVEC protein synthesis but enhanced the inhibitory activity of Shiga toxin. These results are consistent with a role for Shiga toxin in the development of hemolytic-uremic syndrome at the level of the vascular endothelium in humans. PMID- 1937775 TI - Splenic T-lymphocyte functions during early syphilitic infection are complex. AB - Immune regulation during syphilitic infection is extremely complex. This paper presents findings on the early events of T-cell activation following testicular infection in rabbits. Treponema pallidum was preincubated for 24 h with nonadherent spleen cells. After being washed to remove the organisms, these spleen cells were either stimulated with concanavalin A (ConA) to induce interleukin-2 (IL-2), or added to adherent cells that were then stimulated with lipopolysaccharide to induce IL-1. Preincubation with the treponemes up-regulated nonadherent cell functions. These sensitized cells increased their IL-2 production and augmented macrophage IL-1 synthesis. In sharp contrast, if this preincubation step was omitted, down-regulation was apparent. When T. pallidum was directly incubated with nonadherent cells in the presence of ConA, reduced levels of IL-2 were detected. Nonadherent cells from infected rabbits secreted soluble suppressive factors after 48 h of in vitro incubation; these factors inhibited ConA-induced IL-2 generation as well as ConA-induced lymphocyte proliferation. At least some of this suppressive activity was attributed to transforming growth factor. In addition, when T lymphocytes were depleted, less suppression was detected. Treponemes also inhibited ConA-induced T-cell proliferation, and monophosphoryl lipid A reversed this inhibitory effect. Since monophosphoryl lipid A neutralizes T-suppressor activity, these findings further suggest a role for T-suppressor activity during syphilitic infection. Finally, T. pallidum directly stimulated IL-2 synthesis when coincubated with phorbol myristate acetate. This agent reverses the prostaglandin E2 blockage of T-helper cell protein kinase C, a necessary second messenger signal for IL-2 synthesis. In summary, T-cell functions are extremely complex and represent a composite of both stimulation and down-regulation, which occur concurrently but to different degrees. PMID- 1937776 TI - Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa. AB - Killing of Pseudomonas aeruginosa by a 55-kDa bactericidal protein (BP 55), a 30 kDa protein (BP 30), cathepsin G, elastase, and proteinase 3 has been compared. P. aeruginosa was resistant to killing by elastase and proteinase 3. BP 55 at a 50% lethal dose (LD50) of 0.23 micrograms of protein per 5 x 10(6) bacteria per ml killed P. aeruginosa and was far more active than BP 30 and cathepsin G. The LD50s of BP 30 and cathepsin G were 16.9 and 28.3 micrograms of protein per 5 x 10(6) bacteria per ml, respectively. Preincubation of BP 55 or BP 30 with lipopolysaccharide (LPS) from P. aeruginosa inhibited bactericidal activity. The N-terminal amino acid sequence of BP 55 and BP 30 revealed no relationship between the two proteins. However, a monoclonal antibody (AHN-15) reacted with both proteins by Western immunoblot. The bactericidal activity of cathepsin G toward P. aeruginosa appeared to be dependent on the availability of the active site of the enzyme; bactericidal activity was inhibited by phenylmethylsulfonyl fluoride (PMSF) and by the specific cathepsin G inhibitor, Z-Gly-Leu-Phe-CH2Cl. The enzyme and bactericidal activities of cathepsin G were also inhibited by LPS from P. aeruginosa. LPS from P. aeruginosa was shown to be a competitive inhibitor of the enzyme activity of cathepsin G. Elastase enzyme activity was also inhibited noncompetitively by LPS, but the enzyme was not bactericidal. We have concluded that all three bactericidal proteins (BP 55, BP 30, and cathepsin G) may bind to the LPS of the outer membrane of P. aeruginosa. It appears that the enzyme active site must be available for cathepsin G to kill P. aeruginosa and that the active site may be involved in the binding of cathepsin G to P. aeruginosa. PMID- 1937777 TI - Cytopathic effects of Mycoplasma pulmonis in vivo and in vitro. AB - This study was performed to evaluate the cytopathic features resulting from Mycoplasma pulmonis infection of tracheal organ cultures compared to with those seen in in vivo infection and to use this system to determine possible differences in cytopathic effects in two M. pulmonis variants found to cause different diseases in vivo. The attachment of M. pulmonis to respiratory epithelium was similar in vivo and in vitro. Cytopathic effects seen in both systems were also similar in loss of tight junctions between cells and exfoliation of respiratory cells, resulting in exposure of the subepithelial layer. These similarities indicate that the observed tissue damage is initiated by the mycoplasmas rather than by immunologic host responses but does not exclude the possibility that host responses may subsequently contribute to the cytopathological events. Comparison of the effects of the two variants (one known to cause death in vivo) did not reveal differences in vitro. This suggests that host factors (not present in vitro) may account for differences in virulence. Detailed in vitro studies allowed the identification of the time frame corresponding to the in vivo infection and also revealed the limitations of the in vitro system. PMID- 1937778 TI - Identification of RTX toxin target cell specificity domains by use of hybrid genes. AB - The Escherichia coli hemolysin (HlyA) and Pasteurella haemolytica leukotoxin (LktA) are cytolytic toxins encoded by genes belonging to the recently described RTX gene family. These cytotoxins are, respectively, 1,023 and 953 amino acids in length and are encoded by genes within identically organized operons. They share 45% amino acid sequence identities but differ in their target cell specificities. In vitro-derived recombinant hybrid genes between hlyA and lktA were constructed by using restriction endonuclease sites created by oligonucleotide site-directed mutagenesis. The cytolytic activity of hybrid proteins was investigated using as targets sheep erythrocytes and two cultured cell lines from different species (BL3, bovine leukemia-derived B lymphocytes; and Raji, human B-cell lymphoma cells). HlyA is cytolytic to all three cell types. LktA lyses only BL3 cells. Among the hybrid proteins displaying cytolytic activity, the striking finding is that the hemolytic activity of several LktA-HlyA hybrids was independent of any cytolytic activity against either cultured cell species. The hemolytic activity was associated with the HlyA region between amino acids 564 and 739. Structures that are critical for HlyA cytolytic activity against BL3 or Raji cells were destroyed when LktA-HlyA and HlyA-LktA hybrids were made, respectively, at amino acid positions 564 and 739 of HlyA. In contrast to HlyA, which lysed the two different cultured cell lines with equal efficiency, Lkt-HlyA hybrids possessing the amino-terminal 169 residues of LktA lysed BL3 cells more efficiently than Raji cells. This suggests that a significant but not exclusive element of the LktA ruminant cell specificity resides in the amino-terminal one-fifth of the protein. A molecular model of the functional domains of HlyA and LktA is presented. PMID- 1937779 TI - Effects of recombinant gamma interferon and tumor necrosis factor on in vitro interactions of human mononuclear phagocytes with Coccidioides immitis. AB - Human peripheral blood monocytes readily phagocytized Coccidioides immitis endospores (2 to 5 microns) in vitro. Within 24 to 30 h at 37 degrees C, the phagocytized endospores started developing into immature spherules. However, when the monocytes were incubated with recombinant human gamma interferon (rIFN-gamma) or recombinant human tumor necrosis factor alpha (rTNF-alpha) and then infected, fewer endospores developed into spherules. Treatment with rIFN-gamma or rTNF alpha activated the fungicidal capabilities of the monocytes as evidenced by the significant reduction in CFU that could be recovered from rIFN-gamma- or rTNF alpha-activated monocytes compared with nontreated controls. PMID- 1937780 TI - Sulfhydryl-dependent attachment of Treponema denticola to laminin and other proteins. AB - Attachment of Treponema denticola ATCC 35405 to laminin, a major basement membrane protein, and to other proteins was studied. Microdilution plates were coated with the proteins, and the attachment of T. denticola was measured by the enzyme-linked immunosorbent assay technique. Compared with bovine serum albumin (BSA), T. denticola had a high affinity to laminin, fibronectin, fibrinogen, and gelatin, as well as to type I and type IV collagens. Attachment to RGD peptide (Gly-Arg-Gly-Asp-Ser, the integrin recognition sequence) was only about 30% of that to laminin and was comparable to attachment to BSA. Tests with laminin fragments obtained through elastase digestion showed that the spirochetes attached well to an A-chain 140-kDa fragment involved in eukaryote cell attachment but did not attach to a 50-kDa fragment that includes the heparin binding site. Pretreatment of T. denticola with soluble laminin, fibronectin, gelatin, BSA, or fibrinogen had no effect on the attachment of the bacteria to laminin or fibronectin. A wide variety of compounds were tested for their possible inhibitory actions on the attachment. While most treatments of T. denticola ATCC 35405 had little or no effect on the attachment to proteins, sulfhydryl reagents p-chloromercuribenzoic acid (pCMBA) and oxidized glutathione inhibited the attachment by 70 to 99%, depending on the protein. When T. denticola was first allowed to attach to proteins, addition of pCMBA or oxidized glutathione could no longer reverse the attachment. Heat treatment of the spirochetes also markedly reduced the attachment to laminin, gelatin, and fibrinogen but not to BSA. Mixed glycosidase treatment of the spirochetes inhibited the attachment by 20 to 80%. None of the above treatments of the substrate proteins had any marked effect on the spirochete attachment. The results indicate that T. denticola has the capacity to bind to many different kinds of proteins by utilizing specific attachment mechanisms. The binding appears to involve protein SH groups and/or carbohydrate residues on the surface of T. denticola. PMID- 1937781 TI - In vitro binding of Helicobacter pylori to human gastric mucin. AB - The in vitro binding of four Helicobacter pylori strains to human gastric mucin was studied with an enzyme-linked immunosorbent assay. All four strains were found to bind to purified mucin. Neuraminidase treatment and nonspecific oxidation of mucin decreased bacterial adherence to the macromolecule. Mucin preparations were also found to inhibit attachment of H. pylori to HEp-2 monolayers. PMID- 1937783 TI - ADP-ribosylation of p21ras and related proteins by Pseudomonas aeruginosa exoenzyme S. AB - Pseudomonas aeruginosa exoenzyme S ADP-ribosylates p21ras and several related proteins. ADP-ribosylation of p21ras does not alter interactions with guanine nucleotides. The ras-related GTP-binding proteins, including Rab3, Rab4, Ral, Rap1A, and Rap2, are also substrates; given these results, we propose a model for the role of exoenzyme S in pathogenesis. PMID- 1937782 TI - Inhibition of chemotaxis of neutrophil leukocytes to interleukin-8 by endotoxins of various bacteria. AB - The effects of endotoxins from various bacteria (Escherichia coli, Klebsiella pneumoniae, Vibrio cholerae, Shigella flexneri, Salmonella typhosa, and Pseudomonas aeruginosa) on chemotaxis of neutrophil leukocytes to formyl peptide and interleukin-8 were tested in an improved chemotaxis assay involving a "sparse pore" polycarbonate (Nuclepore) membrane in a Boyden-type chamber. The possible chemotactic activity of the endotoxins themselves were tested by the same technique. In addition, the effects of these substances on random motility of neutrophils were tested with a corresponding assay involving similar chambers fitted with membranes of standard pore density. Possible activation of the complement system of serum by each endotoxin was tested with sheep erythrocyte assays and the maximum endotoxin concentration (100 micrograms/ml) used in the chemotaxis and motility assays. All endotoxins inhibited chemotaxis of neutrophils to interleukin-8. No endotoxin affected chemotaxis to formyl peptide or was itself chemotactic for neutrophils. Endotoxin of S. flexneri inhibited random motility of neutrophils, while the others had no such effect. Endotoxins of K. pneumoniae and of P. aeruginosa produced moderate and marked inhibition, respectively, of total complement, as measured by hemolysis of sheep erythrocytes, without affecting the levels of C3c and C4 in these assays. Endotoxins of the other bacteria had no demonstrable effect in any of these assays of complement activation. These results suggest that chemotaxis to interleukin-8 may be mediated by cellular mechanisms different from those involved in chemotaxis to formyl peptide. Furthermore, the presence of these endotoxins could be significant for the suppression of neutrophil accumulation in inflammatory lesions mediated by interleukin-8. PMID- 1937784 TI - Site-specific mutagenesis of the catalytic subunit of cholera toxin: substituting lysine for arginine 7 causes loss of activity. AB - Cholera and pertussis toxins each contain a subunit with ADP-ribosyltransferase activity, sharing a region of nearly identical amino acid sequence near the NH2 terminus. Previous investigations have shown that substitution of a lysine residue for Arg-9 in the catalytic A subunit of pertussis toxin substantially eliminates its enzyme activity. We now report that substitution of lysine for the position-equivalent Arg-7 of cholera toxin subunit A leads to a similar loss of catalytic activity. This result suggests a correlation of function with structure between the sequence-related cholera and pertussis toxin A subunits and may contribute to the design of a vaccine containing an enzymatically inert analog of cholera toxin. PMID- 1937786 TI - The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is antigenic in human infections. AB - Antibodies against the major cysteine proteinase (cruzipain) from Trypanosoma cruzi were detected in human sera obtained from patients with chronic Chagas' disease. Not only the intact 60-kDa enzyme but also its 25-kDa self-proteolysis fragment are antigenic in vivo. Although T. cruzi antigens 13 and 36 also reacted with the apparently monospecific antiproteinase serum, the antigenicity of cruzipain to human patients is genuine, since its reactivity was not modified by the adsorption of human sera with the recombinant proteins 13 and 36. PMID- 1937785 TI - An interleukin-1 inhibitor in gingival crevicular fluid of patients with chronic inflammatory periodontal disease. AB - The gingival crevicular fluid of a patient(s) with marginal periodontal disease contained an activity inhibitory to interleukin-1 (IL-1). The inhibitory activity could be detected after the depletion of IL-1 alpha by the use of a specific antibody (anti-human recombinant IL-1 alpha monoclonal antibody)-conjugated Sepharose column. The inhibitory activity was not due to a toxic effect on the thymocytes since IL-1 alpha-depleted gingival crevicular fluid did not affect the incorporation of [3H]thymidine in either the presence or absence of concanavalin A. The inhibitory activity was exerted against both IL-1 alpha and IL-1 beta. The inhibitory factor did not have any effect on IL-2-induced proliferation of concanavalin A-activated spleen cells. The inhibitor was heat labile. Gel filtration on a Superose 12 column revealed the IL-1 inhibitor to have two major peaks, one in the molecular size range of 12 to 14 kDa and the other below a molecular size of 10 kDa. PMID- 1937787 TI - Virulence-related protein synthesis in Naegleria fowleri. AB - Protein synthesis patterns of the low-virulence Naegleria fowleri LEE strain from axenic culture, the same strain after mouse brain passage to increase virulence, and the same strain after growth on bacteria were studied. Comparisons of accumulated proteins, in vivo-synthesized proteins, and in vitro-synthesized proteins translated from poly(A)+ mRNA were made. Differences between amoebae from the different treatments were noted. After 6 months in axenic culture, pathogenic protein synthesis patterns were lost and there was a decrease in virulence. Therefore, the increase in virulence is correlated with numerous specific changes in protein synthesis. PMID- 1937788 TI - Arylneuraminidase activity of Pseudomonas aeruginosa does not degrade natural substrates such as human respiratory mucins. AB - The culture supernatant from a single Pseudomonas aeruginosa strain has been reported to show neuraminidase activity, leading to the speculation that this bacterium may use this enzyme as a virulence factor to act on host macromolecules. In order to extend this finding, we have examined the activity of concentrated P. aeruginosa culture supernatants and cells on synthetic and natural substrates containing sialic acid, such as human respiratory mucins. Four P. aeruginosa strains showed some activity on the synthetic substrate 4 methylumbelliferyl-alpha-D-N-acetylneuraminic acid but failed to liberate N acetylneuraminic acid from six different natural substrates. Attempts to induce enzyme production by use of human respiratory mucins in the culture medium were also unsuccessful. The supernatants also showed N-acetyl-beta-D-glucosaminidase like activity on a synthetic substrate but did not liberate N-acetylhexosamines from natural substrates. We conclude that the neuraminidase-like activity observed in P. aeruginosa can be defined as an arylneuraminidase and that the possession of a neuraminidase active on natural substrates is not a common attribute of P. aeruginosa strains. PMID- 1937789 TI - Listeriolysin as a virulence factor in Listeria monocytogenes infection of neonatal mice and murine decidual tissue. AB - Listeriolysin is a 60-kDa protein which allows the growth of Listeria monocytogenes in macrophages and other cells and has been shown to be a virulence factor in Listeria infections of adult mice. However, the neonate and fetoplacental unit are major populations susceptible to listeriosis. Recent data indicate that macrophage and T-cell functions are markedly inhibited in these young mice, and the virulence of listeriolysin-negative (HLY-) and listeriolysin positive (HLY+) Listeria cells in the setting of such inhibited macrophage and T cell functions has not previously been examined. We now compare CNL 85/162, a transposon-induced, HLY- Listeria strain, and CNL 85/163, a spontaneous HLY+ revertant. We found that all 18 neonates injected with CNL 85/163 (HLY+) died within 12 days after an injection of 10(4) Listeria cells per mouse. In contrast, all 16 neonates injected with 1,000 times more CNL 85/162 (HLY-) cells survived more than 14 days. Three days after injection, growth of CNL 85/163 (HLY+) in the internal organs was more than 5 log greater than that of CNL 85/162 (HLY-). We also found that CNL 85/162 (HLY-) did not proliferate well in decidual tissue, which is a major component of the placental region. Our studies indicate that HLY bacteria are not virulent in the neonate and the fetoplacental unit despite the inhibited immune functions at these sites. PMID- 1937790 TI - Immunogenicity of Salmonella typhi Ty21a vaccine for young children. AB - An attenuated Salmonella typhi Ty21a vaccine was administered to 18 infants and toddlers (less than or equal to 24 months old) to determine its safety and immunogenicity. The vaccination (10(9) CFU per dose, three doses) was well tolerated. However, after the vaccination there was no evidence of a humoral or cellular immune response to S. typhi. The vaccine used was known to be immunogenic for older children and adults. The results support the view that the immunogenicity of Ty21a is age dependent. PMID- 1937791 TI - Characterization of immunodominant surface antigens of Haemophilus somnus. AB - An immunodominant Haemophilus somnus outer membrane protein with an apparent molecular mass of 40 kDa on Western blots (immunoblots) of gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels was characterized because a monospecific antibody against this antigen was protective. This monospecific antibody was used for immunoaffinity purification of the antigen. The immunoaffinity-purified antigen reacted with a polyclonal antibody to the 40-kDa antigen but not with a monoclonal antibody (3G9) which reacted with the 40-kDa antigen in gradient gels. On 8 or 10% gels, the approximately 40-kDa antigen was resolved as two bands, a 40-kDa band which reacted with the protective monospecific polyclonal antibody (p40) and a band of lower molecular mass which reacted with monoclonal antibody 3G9. The latter antigen was designated p39. Both antigens were conserved in all H. somnus isolates tested. The specific antibodies were also used to detect cross-reacting antigens in other gram-negative bacteria. Antibody to p40 reacted with proteins of 55 to 28 kDa, with the greatest intensity shown among proteins from other members of the family Pasteurellaceae. Antibody to p40 was reduced by absorption with live H. somnus or other members of the family Pasteurellaceae, so the antigen appears to be surface exposed. Antibody to p39 only cross-reacted with a broad band (38 to 40 kDa) in Haemophilus agni. Since H. agni is not a bovine pathogen and since convalescent phase serum from H. somnus-infected animals did recognize p39, the latter may be a good immunodiagnostic antigen, if the lack of cross-reactivity with antigens in other gram-negative bacteria is confirmed with a polyclonal antibody to p39. The cross-reactivity of antiserum to p40 with antigens of members of the family Pasteurellaceae and the ability of this antiserum to protect against H. somnus pneumonia indicate that p40 may be a useful vaccine antigen for H. somnus disease and perhaps even diseases caused by other members of the family Pasteurellaceae. PMID- 1937792 TI - Construction of an eae deletion mutant of enteropathogenic Escherichia coli by using a positive-selection suicide vector. AB - The ability to attach to epithelial cells, efface the microvillus surface, and disrupt the underlying cytoskeleton is characteristic of enteropathogenic Escherichia coli (EPEC). Recently, eae, a gene necessary for this phenomenon, was described (A. E. Jerse, J. Yu, B. D. Tall, and J. B. Kaper, Proc. Natl. Acad. Sci. USA 87:7839-7843, 1990). We report the use of a novel suicide vector containing the pir-dependent R6K replicon and the sacB gene of Bacillus subtilis to construct an eae deletion mutant of EPEC. This system enables positive selection for the loss of vector sequences. The resulting mutant, CVD206, is indistinguishable from the wild-type strain except for the loss of a 94-kDa outer membrane protein and attaching and effacing ability. Both the 94-kDa outer membrane protein and attaching and effacing ability are restored upon reintroduction of the eae gene on a plasmid. These results confirm the role of the eae gene in the attaching and effacing activity of EPEC and establish the utility of a new system for the construction of deletion mutations. PMID- 1937793 TI - Correlation of carotenoid production, decreased membrane fluidity, and resistance to oleic acid killing in Staphylococcus aureus 18Z. AB - Staphylococcus aureus is susceptible to killing by host-derived fatty acids. Studies were performed to test for a correlation between carotenoid production by S. aureus and protection against oleic acid. Oleic acid killing of cells grown in carotenoid expression medium was determined as the dosage of oleic acid in 2 M NaCl-2 mM EDTA that would kill 20% of the cells in 60 min at 37 degrees C (i.e., the 20% lethal dose). Compared with the wild-type strain (18Z), a carotenoid deficient mutant strain (18Z-76) and strain 18Z grown in a medium that suppressed carotenoid production both showed increased sensitivity to oleic acid. Spontaneous revertants of strain 18Z-76 that regained the ability to produce carotenoids were as resistant to oleic acid as the wild-type strain. Oleic acid was shown by fluorescence polarization to decrease polarization values. Lower polarization values indicate a more-fluid membrane. To determine whether protection against oleic acid killing might depend on carotenoid stabilization of membranes, fluorescence polarization values were determined for strains showing different levels of carotenoid production. An indirect correlation was found between membrane fluidity and carotenoid production. We were able to conclude that there is a direct correlation between carotenoid production (i.e., cell pigmentation), cell membrane stability, and resistance to oleic acid-induced cell killing. PMID- 1937794 TI - Immunization of guinea pigs with recombinant TmpB antigen induces protection against challenge infection with Treponema pallidum Nichols. AB - Treponema pallidum-susceptible guinea pigs of strain C4D were immunized with recombinant T. pallidum antigens TmpA, TmpB, TmpC, and TmpA plus TmpB plus TmpC; with Escherichia coli membranes; or with adjuvant alone. Animals in groups of five received six immunizing injections, each of 100 micrograms of antigen incorporated in RIBI adjuvant. After the sixth immunization, all experimental and nonimmunized controls were intradermally challenged with 3 x 10(6) T. pallidum Nichols freshly extracted from infected rabbit testes. Although high titers of antitreponemal antibodies in the fluorescent-treponemal-antibody test or an enzyme-linked immunosorbent assay were evoked in all animals immunized with recombinant antigens, only guinea pigs receiving TmpB antigen demonstrated protection expressed by the development of significantly (P less than 0.01) smaller, atypical lesions of significantly (P less than 0.01) shorter duration and devoid of or containing fewer T. pallidum organisms than lesions in the remaining immunized and control animals. PMID- 1937795 TI - Specificity of antibodies to O-acetyl-positive and O-acetyl-negative group C meningococcal polysaccharides in sera from vaccinees and carriers. AB - Most group C Neisseria meningitidis strains produce an O-acetyl-positive polysaccharide, a homopolymer of alpha-2----9-linked N-acetylneuraminic acid with O-acetyl groups at the C-7 and C-8 of its sialic acid residues. The majority of disease isolates have been reported to contain this polysaccharide. Some strains produce group C polysaccharide lacking O-acetyl groups. The licensed vaccine contains the O-acetyl-positive polysaccharide. We have measured the antibody specificities to the two polysaccharides in sera from asymptomatic group C meningococcal carriers and vaccinated adults by a new enzyme-linked immunosorbent assay (ELISA) procedure using methylated human serum albumin for coating the group C polysaccharide onto microtiter plates. Inhibition of binding of serum antibodies to polysaccharide-coated plates was measured by ELISA after incubation with O-acetyl-positive and O-acetyl-negative group C polysaccharides. Greater inhibition of binding of carrier sera was observed with the homologous polysaccharide. There was substantial inhibition of binding of vaccinee sera to the O-acetyl-positive polysaccharide-coated plate following preincubation with O acetyl-positive polysaccharide, but homologous inhibition on plates coated with the O-acetyl-negative polysaccharide required much higher concentrations of polysaccharide. Carrier sera may have a higher proportion of antibodies with greater specificity for the O-acetyl-negative polysaccharide, while vaccinee sera contain antibodies with greater affinity for the O-acetyl-positive polysaccharide. Studies with monoclonal antibodies specific for O-acetyl-positive and O-acetyl-negative polysaccharides reveal that the percentage of group C meningococcal disease caused by O-acetyl-negative strains remains about 15%, as found over 15 years ago. PMID- 1937796 TI - Effect of elevated environmental temperature on the antibody response of mice to Trypanosoma cruzi during the acute phase of infection. AB - When held at 36 degrees C, Trypanosoma cruzi-infected C3H mice survive an otherwise lethal infection with significantly decreased parasitemia levels and enhanced immune responsiveness. Treatment of T. cruzi-infected mice with the immunosuppressive agent cyclophosphamide indicated that the positive effects of increased environmental temperature were primarily due to enhancement of immunity. A parasite-specific, enzyme-linked immunosorbent assay and immunoblot analysis were used to examine the effect of elevated environmental temperature on the production of anti-T. cruzi antibodies. Both the reactivity and diversity of anti-T. cruzi antibodies were found to be lower in infected mice held at 36 degrees C than in infected mice held at room temperature. However, reactivity and diversity could be enhanced by vaccination with culture forms of the parasite. PMID- 1937797 TI - Antibody responses in the lungs of mice following oral immunization with Salmonella typhimurium aroA and invasive Escherichia coli strains expressing the filamentous hemagglutinin of Bordetella pertussis. AB - The filamentous hemagglutinin (FHA) of Bordetella pertussis was expressed in the attenuated aroA mutant of Salmonella typhimurium, SL3261, and in a strain of Escherichia coli harboring Shigella flexneri plasmid pWR110, which encodes bacterial invasiveness for epithelial cells. Expression of FHA in these strains did not interfere with their ability to invade Henle cells. Immunoglobulins A and G specific for FHA were detected in lung washes of mice following oral immunization with the live recombinant organisms; antibody levels were significantly higher than those in mice immunized with killed bacteria administered orally or intraperitoneally. Live oral vaccines carrying protective antigens of B. pertussis may be an important alternative to new-generation component vaccines against whooping cough. PMID- 1937799 TI - Helminthotoxic responses of intestinal eosinophils to Trichinella spiralis newborn larvae. AB - Because the gastrointestinal lamina propria is the first line of defense against invasion with Trichinella spiralis newborn larvae, we investigated the helminthotoxic characteristics of isolated lamina propria eosinophils. Eosinophils were isolated from the intestinal lamina propria of rats and purified to nearly 90% purity by a combination of velocity sedimentation through Percoll and unit gravity sedimentation through a continuous gradient of bovine serum albumin. Isolated eosinophils were of high viability and responded to surface receptor stimulation. Freshly isolated intestinal eosinophils lacked cytotoxic capacity when incubated with newborn larvae in the presence of specific antiserum. Peritoneal eosinophils from the same rats exhibited 100% helminthotoxicity after 24 h. Cytotoxicity could be stimulated in the intestinal eosinophils by the addition of recombinant murine interleukin-5. PMID- 1937798 TI - High-affinity binding of the basement membrane proteins collagen type IV and laminin to the gastric pathogen Helicobacter pylori. AB - The ability of 16 isolates of the human gastroduodenal pathogen Helicobacter pylori to bind 125I-radiolabelled tissue proteins was quantitated by liquid-phase assay. While capable of binding generally low levels of collagen types I and II, vitronectin, and fibronectin (average binding, 8%; highest binding, 23%), the various H. pylori isolates were good binders of the basement membrane proteins collagen type IV and laminin (average binding, 27%; highest binding, 60%). Campylobacter species tested bound lower levels of collagen type IV and laminin (average binding, 12%; highest binding, 17%). Trypsin and proteinase K treatment of H. pylori cells markedly reduced the binding of collagen type IV and laminin, as did heat treatment, suggesting that the binding of basement membrane proteins is mediated by bacterial surface proteins. Binding of both basement membrane proteins was rapid and saturable. 125I-collagen type IV binding to H. pylori 915 was inhibited by preincubation with unlabelled collagen type IV but was not inhibited by laminin or a number of other proteins. Once bound, radiolabelled collagen type IV but was not displaced by an excess of unlabelled collagen type IV, indicating that the binding interaction was of high affinity. Binding of laminin was partially reversible, and analysis in a solid-phase nonradiolabel assay showed that the interaction was of high affinity, with a Kd of 7.9 nM. This interaction was affected by salt, indicating the presence of a hydrophobic component in the ability of H. pylori to bind laminin. PMID- 1937800 TI - Protective immunity to a blood-feeding nematode (Haemonchus contortus) induced by parasite gut antigens. AB - To determine the ability of gut antigens to induce a protective immune response against blood-feeding nematodes, isolated gut antigens were used to immunize goats against Haemonchus contortus. Immunization-induced antibody responses recognized parasite gut antigens which were associated predominantly with the microvillous membrane region of the parasite gut. Antibody from immune serum also recognized seven predominant gut proteins on a Western blot (immunoblot). Several of these proteins appeared to be integral membrane proteins on the basis of their solubility in the detergent Triton X-114, indicating that the presentation protocol stimulated an antibody response to microvillous membrane antigens. Three different age groups of goats ranging from less than 6 months to greater than 1 year were immunized for challenge experiments. After infection with 10(4) larvae, an 87 to 95% reduction in fecal egg counts for all age groups of goats was achieved in the immunized compared with the control group. The reduction of worms in immunized goats ranged from 65% (kids) to 89% (yearlings) compared with controls. These results indicate that gut antigens can induce significant protection against blood-feeding nematodes. Antibody to H. contortus gut antigens also cross-reacted with microvilli of other blood-feeding nematodes including Ostertagia ostertagi and small strongyles of horses, which indicates that epitopes associated with the gut are phylogenetically conserved. PMID- 1937802 TI - Isolated hepatic granulomas from mice infected with Schistosoma mansoni contain nerve growth factor. AB - Nerve growth factor (NGF) is a neurotrophic factor essential for the development and maintenance of specific neuronal cell populations. In addition, NGF has biological effects on inflammatory cells. The aim of this study was to determine whether NGF is present in chronic inflammation, using isolated hepatic granulomas from mice infected with Schistosoma mansoni as the model. The schistosome granuloma is a complex T-cell-mediated immune response to the egg. Intact granulomas were isolated from the livers of infected mice and examined for the presence of NGF. In homogenized granuloma samples, radioimmunoassay and immunoblotting analyses detected an immunoreactive NGF that had the same molecular mass as that of purified murine NGF (13 kDa). Isolated granulomas cultured in vitro released soluble factor(s) with NGF-like neurite-promoting activity in a rat pheochromocytoma (PC12) bioassay. This activity was partially inhibited by a blocking anti-NGF antibody. There were two potential sources of this NGF-like neurite-promoting activity, either the schistosome egg or the host inflammatory response. Since neither isolated eggs nor soluble egg antigen had neurite-promoting activity, the inflammation was the source of this activity. The inability of the anti-NGF antibody to inhibit completely the granuloma-induced neurite outgrowth in the bioassay signifies that NGF is not the only neurotrophic factor present in these granulomas. The presence of NGF within the granulomas may indicate that NGF has a role in the granulomatous response. PMID- 1937801 TI - Identification of monoclonal antibody-binding domains within antigen P1 of Streptococcus mutans and cross-reactivity with related surface antigens of oral streptococci. AB - Eleven monoclonal antibodies (MAbs) specific for P1, the major protein surface antigen of Streptococcus mutans serotype c, were characterized by Western blot (immunoblot) analysis and by radioimmunoassay using whole bacterial cells. The approximate binding domains of the MAbs were determined by using full-length and truncated P1 polypeptides. The accessibility of these binding sites on the surfaces of intact bacteria was determined by radioimmunoassay. The ability of each MAb to cross-react with related proteins from strains of S. mutans serotypes e and f, S. sanguis, and S. sobrinus serotype g is also reported. PMID- 1937803 TI - Preparation, characterization, and immunogenicity of conjugates composed of the O specific polysaccharide of Shigella dysenteriae type 1 (Shiga's bacillus) bound to tetanus toxoid. AB - The background for developing conjugate vaccines for shigellosis composed of the O-specific polysaccharide (O-SP) bound to a protein is described elsewhere (C. Y. Chu, R. Schneerson, and J. B. Robbins, submitted for publication). Briefly, there is direct evidence for type (lipopolysaccharide [LPS])-specific protection after infection with the wild type or with attenuated strains of shigellae. Prospective studies of Israeli armed forces recruits show a correlation between preexisting serum immunoglobulin G (IgG) LPS antibodies and resistance to shigellosis (D. Cohen, M. S. Green, C. Block, R. Slephon, and I. Ofek, J. Clin. Microbiol. 29:386 389, 1991). In order to elicit IgG LPS-specific antibodies to Shigella dysenteriae type 1, the O-SP of this pathogen was purified and bound to tetanus toxoid (TT) by three schemes. The most immunogenic used a modification of a published method (C. Y. Chu, R. Schneerson, J. B. Robbins, and S. C. Rastogi, Infect. Immun. 40:245-256, 1983). The resultant O-SP-TT conjugates were stable and elicited high levels of IgG O-SP antibodies and booster responses in young mice when injected subcutaneously in saline at 1/10 the proposed human dose. Adsorption onto alum or concurrent administration with monophosphoryl lipid A enhanced both the IgG and IgM antibody responses to the O-SP of the conjugate; both the nonadsorbed and adsorbed conjugates elicited higher rises of IgG than of IgM antibodies. Clinical evaluations of S. dysenteriae type 1 O-SP-TT conjugates are planned. PMID- 1937804 TI - Protective efficacy of a 62-kilodalton antigen, HIS-62, from the cell wall and cell membrane of Histoplasma capsulatum yeast cells. AB - We reported previously that a detergent extract of the cell wall and cell membrane of Histoplasma capsulatum yeast cells contains antigens recognized by T cells. In T-cell immunoblot analysis, a region encompassing 62 kDa was stimulatory for an H. capsulatum-reactive T-cell line and T-cell clones derived from C57BL/6 mice. In this study, we isolated a 62-kDa band, termed HIS-62, from electrophoresed cell wall and cell membrane of H. capsulatum yeast cells and examined its antigenicity and immunogenicity. C57BL/6, BALB/c, and CBA/J mice that were immunized with viable H. capsulatum yeast cells mounted a delayed-type hypersensitivity response to HIS-62 that was stronger than that of normal controls. Spleen cells from each strain of mouse immunized with viable yeast cells proliferated vigorously in response to HIS-62; conversely, splenocytes from control animals did not recognize this antigen. A T-cell line and 5 of 5 T-cell clones from C57BL/6 mice, 10 of 15 BALB/c T-cell hybridomas, and 8 of 12 CBA/J T cell hybridomas recognized HIS-62. A cutaneous delayed-type hypersensitivity response to the antigen was apparent in each strain of mouse that was injected with 80 micrograms of HIS-62 mixed with Freund adjuvant. In addition, spleen cells from HIS-62-immunized mice proliferated in vitro in response to this antigen. Vaccination of each strain of mouse with 80 micrograms of HIS-62 conferred protection against a lethal intravenous challenge with H. capsulatum yeast cells. Thus, HIS-62 appears to be an important target of the cellular immune response to H. capsulatum and induces a protective immune response in mice. PMID- 1937805 TI - Mobilization of F-actin and clathrin during redistribution of Chlamydia trachomatis to an intracellular site in eucaryotic cells. AB - Immunofluorescence was used to examine the distribution of Chlamydia trachomatis serovars L2 and E, F-actin, and clathrin in infected McCoy and HeLa cells. After incubation at 4 degrees C, C. trachomatis serovar L2 was randomly distributed on the McCoy cell surface. After a temperature shift to 37 degrees C, chlamydiae redistributed, within 30 min, to one local aggregate in the central or perinuclear region of individual cells. About 90% of these aggregated chlamydiae were intracellularly localized, but some remained randomly distributed on the cell surface. Similar results were obtained with HeLa cells and C. trachomatis serovar E, except that the redistribution was slower in HeLa cells than in McCoy cells and fewer cells infected with serovar E exhibited a local aggregate than those infected with serovar L2. Cytochalasin D inhibited more than 90% of this local aggregation. Instead, in cytochalasin D-treated cells, the entry of chlamydiae was inhibited and the organisms became localized on the cell surface in a peripheral local aggregate that distributed in a manner similar to that of phalloidin-stained actin. In a double immunofluorescence assay, F-actin and clathrin aggregated correspondingly in time and position with central or perinuclear aggregation of chlamydiae. These results indicate that polymerized actin and clathrin participate in a rapid redistribution of chlamydiae to an intracellular aggregate. PMID- 1937806 TI - Analysis of Aspergillus nidulans conidial antigens and their prevalence in other Aspergillus species. AB - Aspergillus nidulans is an ascomycetous fungus that reproduces asexually by forming multicellular conidiophores and uninucleate spores called conidia. These elements constitute the main vehicle for the transmission of this and other pathogenic Aspergillus species and are the starting point of the different forms of aspergillosis. In order to use A. nidulans as a potential source of useful antigens for the immunodiagnosis of these diseases, we have examined the total protein composition of conidial extracts of this fungus by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis in gels of different percent T. Injection of SDS-extracted conidial proteins into rabbits allowed us to raise a battery of polyclonal antibodies which have defined some important immunogenic polypeptides. Several of these immunogens were both present in mycelial extracts and recognized by antimycelium antibodies. Four of them, designated cdA, cdB, cdC, and cdE, were also found in conidial extracts of other pathogenic Aspergillus species. Only cdE was undetectable in cell extracts of the nonrelated species Fusarium culmorum and Phycomyces blakesleeanus. PMID- 1937807 TI - Testosterone-induced abrogation of self-healing of Plasmodium chabaudi malaria in B10 mice: mediation by spleen cells. AB - This study investigates the suppressive effect of testosterone (Te) on the self healing of Plasmodium chabaudi malaria in female mice of the strain C57BL/10, and, in particular, the possible role of spleen cells in mediating this Te effect. Our data show the following. (i) About 80% of B10 mice infected with 10(6) P. chabaudi-infected erythrocytes are capable of self-healing the infections. This capability is progressively impaired and finally abrogated after pretreating the B10 mice with Te for 3 weeks. (ii) The spleen is Te responsive. This becomes evident in a reduction of total spleen cells from 1.05 x 10(8) to 0.54 x 10(8) on average after Te treatment for 3 weeks. Moreover, Te treatment causes an increase in the relative proportion of CD8+ cells by about 4% and a decrease of Ig+ cells by about 4.5%, as revealed by flow cytometry. (iii) Spleen cells mediate the suppressive Te effect as revealed by adoptive transfer experiments. The percentage of self-healing mice dramatically decreases to about 8% when they receive, just prior to infection, nucleated spleen cells isolated from mice treated with Te for 3 weeks. This suppressive effect can be transferred by T cells in particular but also by non-T cells, though to a lesser extent. (iv) The adoptively transferred cells mediate their suppressive effect on self-healing only if the recipient mice receive Te during infection. Our data suggest that spleen cells become functionally changed by the Te treatment for 3 weeks. Particularly T cells, but also non-T cells, gain P. chabaudi-specific suppressive activities, and the cells require a Te-induced factor(s) to mediate these activities. PMID- 1937808 TI - Differential induction of tumor necrosis factor by bacteria expressing rough and smooth lipopolysaccharide phenotypes. AB - The lipid A portion of the lipopolysaccharide (LPS) molecule of gram-negative bacteria has the ability to turn on the production of tumor necrosis factor (TNF) in macrophage cells. The question addressed in this paper was whether the presence of the polysaccharide moiety on the LPS molecule had any bearing on this ability. The question was asked (i) by using isolated LPS from a series of Salmonella mutants having progressively less polysaccharide attached to the lipid A portion of the molecule and (ii) by using whole bacteria expressing alternatively the smooth or rough LPS phenotype. Isolated LPS and bacteria were examined for their abilities to induce bioactive TNF in the mouse macrophage cell line RAW 264.7. The results indicated that the presence of long- or short-chain polysaccharide moieties had no bearing on the ability of the isolated LPS molecule to induce TNF. However, the presence of long-chain polysaccharides attached to the lipid moiety on the intact smooth bacterium was associated with a decreased ability to induce TNF. To test whether the bacteria were inducing TNF by a cell (bacterium)-to-cell (macrophage) contact mechanism or through a releasable product, the bacteria were removed from direct contact with the macrophage cells by using a Transwell filter insert. Under these conditions the rough bacteria continued to induce TNF, while the smooth bacteria were no longer capable of doing so. When filtrates from the bacteria were examined in the Limulus amebocyte lysate assay, the results showed that the rough bacteria were releasing approximately a log order more Limulus amebocyte lysate activity than the smooth bacteria. The results of this study suggest that rough bacteria may be superior inducers of TNF compared with their smooth counterparts because of a greater propensity to shed their LPS. PMID- 1937809 TI - Cytolysins of Actinobacillus pleuropneumoniae serotype 9. AB - Cytolysin I (ClyI) and cytolysin II (ClyII), which are present in the culture supernatant of Actinobacillus pleuropneumoniae serotype 9, are thought to play an important role in the pathogenesis of pig pleuropneumonia. The purpose of this study was to clone and characterize the genetic determinants of these cytolysins. Cloning was accomplished by the screening of DNA libraries for the presence of cytolytic activity and for the presence of DNA sequences homologous to leukotoxin DNA of Pasteurella haemolytica. Both genetic determinants were found to be members of the RTX cytotoxin family. The ClyII determinant was characterized in more detail. It appeared that ClyII more closely resembled the leukotoxin of P. haemolytica than the alpha-hemolysin of Escherichia coli. The ClyII amino acid sequence was identical to a hemolysin gene sequence of A. pleuropneumoniae serotype 5; this finding indicates that the latter gene also codes for ClyII and not for ClyI, as has previously been suggested. The genetic organization of the ClyII determinant differed from the genetic organization of other RTX determinants. Genes responsible for secretion of ClyII were not contiguous with the toxin gene. Instead, secretion genes were present elsewhere in the genome. These secretion genes, however, belong to the ClyI operon. This indicates that the secretion genes of the ClyI operon are responsible for secretion of ClyI and ClyII. PMID- 1937810 TI - Heparin protects human endothelial cells infected by Rickettsia rickettsii. AB - Routine culture of endothelial cells currently includes the use of heparin, which significantly reduces cell doubling time and increases cell population size. Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolites produced by the action of xanthine and xanthine oxidase. Because of our hypothesis implicating free radicals in cell injury caused by Rickettsia rickettsii, we have carried out a series of experiments to examine the effects of heparin on injury to endothelial cells infected by this microorganism. These studies showed that heparin does not inhibit replication of R. rickettsii in the cytoplasm of endothelial cells. Furthermore, heparin appears to exhibit a protective effect on the infected host cell as measured by (i) reduced plaque size, (ii) increased longevity of the cell monolayer, (iii) reduction in the amount of lactic dehydrogenase released from infected cells, and (iv) reduction in the levels of intracellular peroxides formed in infected cells. Electron microscopic studies also show a significant reduction in dilatation of the rough surfaced endoplasmic reticulum of the infected cells in the presence of heparin. These observations appear to lend additional support to involvement of an oxidative mechanism in human endothelial cell injury caused by R. rickettsii. PMID- 1937812 TI - Effects of gamma interferon, tumor necrosis factor alpha, and interleukin-2 on infection and proliferation of Theileria parva-infected bovine lymphoblasts and production of interferon by parasitized cells. AB - Theileria parva is a protozoan parasite that infects bovine B cells and alpha beta and gamma delta T cells and transforms them into continually proliferating cells. CD4+ T. parva-antigen-specific immune T cells have been shown to produce cytokines in response to stimulation with parasitized cells, and T. parva infected lymphocytes produce and consume T-cell growth factors and interleukin-2 (IL-2). To ascertain the role of T-cell cytokines on T. parva infections, we evaluated recombinant gamma interferon (rIFN-gamma), rIL-2, and tumor necrosis factor alpha (rTNF-alpha) for their effects on establishment, proliferation, and survival of parasitized cells. The results indicate that neither rIFN-gamma nor rTNF-alpha had an enhancing or inhibitory effect on the growth of established T. parva-infected T-cell clones, whereas bovine rIL-2 increased the proliferation of infected B-cell and alpha beta T-cell clones but not that of gamma delta T-cell clones. To evaluate the effects of the cytokines on establishment of parasitized cell lines, peripheral blood mononuclear cells were cultured in their presence immediately following infection with T. parva sporozoites. Neither rIFN-gamma nor rIL-2 altered the proportion of cells initially developing schizonts, but both enhanced establishment of infected cell lines by about twofold. In contrast, rTNF alpha resulted in about a 33% decrease in the proportion of schizont-infected cells. Inhibitory effects on establishment of parasitized cell lines by rTNF alpha were no longer apparent by 12 days following infection. Tests conducted during this study indicated that T. parva-infected lymphocytes also spontaneously produce IFN that is neutralized by acidic pH treatment. In conclusion, we speculate that none of these T-cell cytokines are likely to have a profound inhibitory effect in vivo on T. parva infections. Instead, IFN-gamma and IL-2 may facilitate the establishment of infection by T. parva. PMID- 1937811 TI - The outer membrane of Pasteurella multocida 3:A protects rabbits against homologous challenge. AB - The protective efficacy of a vaccine purified from the Pasteurella multocida 3:A outer membrane (OM) was evaluated in rabbits by homologous challenge. Twenty seven rabbits were divided into four groups: 1, vaccinated with OM and challenged; 2, nonvaccinated and challenged; 3, vaccinated with OM only; and 4, nonvaccinated and not challenged. Rabbits were immunized intranasally with 1 mg of OM protein on days 0, 7, 14, and 35, challenged intranasally on day 49, and killed on day 63. Mortality rates were 0, 67, 0, and 0% for groups 1 through 4, respectively. The prevalence of pneumonia was reduced from 73 (group 2) to 20% (group 1). The severity of pneumonia was reduced from 0.62 (group 2) to 0.07 (group 1), as measured by the group lesion index. The number of P. multocida in nasal cavities was reduced from 3.89 x 10(5) (group 2) to 6.19 x 10(2) (group 1). The geometric mean number of P. multocida in lungs was 8,360,000-fold less in group 1 than in group 2. Similarly, the prevalence of P. multocida colonization in nonrespiratory organs was reduced from 47 (group 2) to 4% (group 1). Furthermore, group 1 and 3 rabbits developed significantly elevated immunoglobulin A antibodies in nasal secretions and lung lavages and significantly elevated immunoglobulin G antibodies in lung lavages and sera. In addition, rabbit immune sera contained antibodies against P. multocida OM proteins and lipopolysaccharides and inhibited P. multocida proliferation in mouse lungs. These results indicate that a vaccine prepared from the OM of P. multocida provides a significant protection in rabbits against homologous challenge. PMID- 1937813 TI - Sugar metabolism by fusobacteria: regulation of transport, phosphorylation, and polymer formation by Fusobacterium mortiferum ATCC 25557. AB - Strains of eight Fusobacterium species differed in the ability to use sugars as energy sources for growth. For Fusobacterium russii ATCC 25533, F. gonidiaformans ATCC 25563, and F. nucleatum ATCC 10953 (except for fructose), growth was marginal to poor on all of the sugars tested. Other species displayed reasonable growth on glucose, fructose, mannose, and galactose, and two strains of F. mortiferum (ATCC 25557 and ATCC 9817) grew well on six of the sugars tested, including sucrose and maltose. Glucose transport by resting cells of most of the species was dependent upon (or markedly stimulated by) the presence of a fermentable amino acid. By contrast, F. mortiferum cells rapidly accumulated glucose and other sugars in the absence of amino acids. Although these cells were constitutive for glucose uptake, accumulation of other sugars was specifically induced by growth of F. mortiferum on the appropriate sugar. Spectrophotometric analyses and in situ staining of anionic polyacrylamide gels showed that glucose and fructose (mannose) are phosphorylated by separate ATP-dependent kinases. Fructokinase was stable in air at 4 degrees C, but under these conditions, greater than 70% of the glucokinase activity was lost. After overnight dialysis of the extract, no glucokinase activity was detectable; however, 65% of the initial enzyme activity was retained by inclusion of 1 mM dithiothreitol in the dialysis buffer. Thin-section electron microscopy showed that cells of F. mortiferum produced various amounts of intracellular glycogen during growth on the following sugars (in decreasing order of formation): galactose greater than sucrose greater than glucose greater than mannose greater than fructose. Mechanisms for sugar transport regulation, phosphorylation, and polymer synthesis by F. mortiferum cells are proposed. PMID- 1937814 TI - Relation between structure and immunologic properties of the Vi capsular polysaccharide. AB - The Vi capsular polysaccharide of Salmonella typhi is a linear homopolymer of poly-alpha(1----4)GalNAcp variably O acetylated at the C-3 position. Serum antibodies elicited by this antigen confer protective immunity against typhoid fever. The relation between the immunologic properties and structure of Vi was investigated by carboxyl reduction, O deacetylation, and acid hydrolysis. The immunogenicity of Vi was closely related to its degree of O acetylation. Partial O deacetylation slightly increased immunogenicity; complete O deacetylation eliminated the immunogenicity of Vi. O-deacetylated Vi, however, still reacted with antisera prepared by injection of whole bacteria. Carboxyl reduction, in contrast, had a comparatively slight effect upon both the immunogenicity and antigenicity of Vi. Retention levels of antigenicity after acid treatment were greater for both the native and carboxyl-reduced Vi than for the O-deacetylated product. The Courtauld-Koltun space-filling model of a pentamer of Vi demonstrated that the bulky nonpolar O-acetyls, which protrude in rows on both sides, make up most of the surface. The carboxyls are less exposed and are partially shielded by the O-acetyls. The molecular model thus provides an explantation for the dominant role of the O-acetyls, as well as the lesser effect of carboxyl reduction, upon the immunologic properties of Vi. PMID- 1937815 TI - Intracellular targeting of the Yersinia YopE cytotoxin in mammalian cells induces actin microfilament disruption. AB - Pathogenic Yersinia spp., including the etiological agent of plague, Y. pestis, all carry a common plasmid that encodes a number of essential virulence determinants, the Yop proteins. One of these, YopE, has been shown to be involved in the obstruction of the primary host defense by a molecular mechanism leading to inhibition of phagocytosis (R. Rosqvist, A. Forsberg, M. Rimpilainen, T. Bergman, and H. Wolf-Watz, Mol. Microbiol. 4:657-667, 1990). Although the Yop proteins are secreted into the culture supernatant in vast amounts, in vitro studies of the function of the Yop proteins have so far been unsuccessful. We show that isolated Yop proteins indeed can cause cytotoxic effects in vitro if the proteins are introduced intracellularly into the eukaryotic cell. Isolated Yop proteins of Yersinia pseudotuberculosis were found to disrupt the microfilament structure when microinjected intracellularly into the host cell. In particular, YopE was demonstrated to be directly involved in the cytotoxic action, whereas YopD seems to have a critical role in translocating the YopE protein through the host cell membrane. These results elucidate the requirement for at least some of the Yop proteins to leave the pathogen during infection. PMID- 1937816 TI - Protective role of bovine neutrophils in Pasteurella haemolytica-mediated endothelial cell damage. AB - The purpose of this study was to determine if Pasteurella haemolytica can directly injure bovine pulmonary endothelial cells (EC) and if neutrophils have a beneficial or detrimental role in bacterium-EC interaction. Various combinations of live P. haemolytica, heat-killed P. haemolytica, anti-P. haemolytica immune serum, polymyxin B, and bovine neutrophils were added to confluent monolayers of bovine EC. Monitoring included determination of 51Cr release from EC, phase microscopy, and transmission electron microscopy. Although toxic changes were not evident at 5 h postinoculation, both live and heat-killed P. haemolytica produced extensive EC damage by 22 h postinoculation. Damage by live P. haemolytica was prevented only when both neutrophils and immune serum were used. Polymyxin B effectively prevented the toxic effect of heat-killed P. haemolytica, suggesting that lipopolysaccharide was the major toxic factor. Morphological studies showed close apposition of P. haemolytica to EC membranes, neutrophil activation, and adherence to EC but no evidence of neutrophil-associated EC membrane damage. These studies demonstrate that neutrophils and immune serum in combination are effective in preventing EC damage mediated by live P. haemolytica. PMID- 1937817 TI - Antibody to a 145-kilodalton outer membrane protein has bactericidal activity and protective activity against experimental bacteremia caused by a Brazilian purpuric fever isolate of Haemophilus influenzae biogroup aegyptius. The Brazilian Purpuric Fever Study Group. AB - The immunologic basis for protection against Brazilian purpuric fever, a septicemic infection associated with Haemophilus influenzae biogroup aegyptius bacteremia, is unknown. Passive immunization of infant rats with antiserum to whole bacterial cells of the homologous strain protects them from experimental bacteremia following bacterial challenge. In immunoblotting, antibody to a 145 kDa protein (P145) was present in protective antisera but not in nonprotective antisera. As judged by analysis of the antibodies eluted from whole bacterial cells and the agglutination of bacteria by antisera to P145, this protein is surface exposed. We prepared monospecific rat antisera to this protein by three methods: (i) immunization with whole bacterial cells and absorption with a Brazilian purpuric fever strain not expressing P145, (ii) immunization with gel purified P145, and (iii) immunization with a P145-expressing transformant of a laboratory H. influenzae strain expressing this protein and absorption of the antiserum with the laboratory H. influenzae strain. These antisera had low antilipooligosaccharide antibody titers, were reactive only with P145, and had bactericidal activity in vitro. Following passive immunization, these antisera partially protected infant rats from bacteremia resulting from intraperitoneal challenge with bacteria. As assessed by immunoblotting, pooled adult human sera contained antibodies reactive with P145. Antibody to P145 may contribute to protection against Brazilian purpuric fever. PMID- 1937818 TI - Immunosuppressive effects of Prevotella intermedia on in vitro human lymphocyte activation. AB - In this study, we have assessed four strains of Prevotella intermedia, isolated from periodontally involved lesions, for their ability to inhibit lymphocyte functions. All four strains were found to cause a dose-dependent inhibition of B- and T-cell proliferation in response to mitogens and antigens. This was reflected in altered DNA, RNA, and protein syntheses. Furthermore, P. intermedia appeared to affect the early stages of cell activation. This was ascertained by kinetic analysis in which it was determined that the extract had to be present during the first 24 h of incubation to cause suppression. Moreover, direct assessment of the early stages of cell activation indicated that release of cytokines and expression of the interleukin 2 receptor and CD69 on T cells were inhibited by P. intermedia sonic extracts. Finally, preliminary characterization of the immunosuppressive agent indicates that it has a molecular mass of approximately 50 kDa and is heat labile. It has been proposed that impaired host defense may play a pivotal role in the pathogenesis of many infections. The data presented in this paper suggest that microbially mediated immunosuppression may contribute to the pathogenesis of periodontal disease by altering the nature and consequences of host-parasite interactions. PMID- 1937819 TI - Nuclease-sensitive binding of an Actinobacillus actinomycetemcomitans leukotoxin to the bacterial cell surface. AB - A leukotoxin of Actinobacillus actinomycetemcomitans 301-b was solubilized from cell-associated membrane vesicles by treatment with externally added DNase and RNase and was further purified by a procedure which included ammonium sulfate fractionation, gel filtration chromatography, and ion-exchange chromatography. The purified toxin had a molecular mass of 113,000 Da by sodium dodecyl sulfate polyacrylamide gel electrophoresis and a high isoelectric point (approximately 8.8). From these characteristics, it was to be expected that the membrane vesicle toxin was almost identical to the leukotoxin extracted with polymyxin B in an earlier study (C.-C. Tsai, B. J. Shenker, J. M. DiRienzo, D. Malamud, and N. S. Taichman, Infect, Immun. 43:700-705, 1984). The treatment with DNase and RNase was also highly effective for solubilizing the leukotoxin directly from whole cells, suggesting that the toxin is secreted extracellularly but retained in nucleic acids on the outermost surface of bacterial cells. PMID- 1937820 TI - Role of a cell surface-associated protein in adherence and dental caries. AB - Insertional inactivation of the Streptococcus mutans spaP gene was used to construct an isogenic mutant (834) of strain NG8 (serotype c) which lacked the major cell surface-associated protein referred to as P1 (15). Results of several studies suggest that P1 is involved in the adherence of S. mutans to saliva coated apatite surfaces. With an in vitro model system of hydroxyapatite (HA) beads coated with parotid saliva (PS) and additional HA surfaces coated with PS and in situ-formed glucan, it was observed that mutant 834 adhered poorly to the PS/HA surfaces. In contrast, both parent and mutant strains bound to the PS glucan/HA surface. Groups of intact and desalivated rats were infected with each strain to determine relative capacities to induce dental caries. Rats were fed a highly cariogenic diet containing 56% sucrose for 3 to 5 weeks. Each strain colonized the rodent model and caused similar levels of smooth-surface caries under these dietary conditions. It was concluded that P1 influences the ability of organisms to adhere to saliva-coated surfaces and possibly affects primary colonization of the oral cavity in the absence of a glucan surface but has no effect on glucan-mediated adherence in vitro or in vivo. PMID- 1937821 TI - Sexual stage development of cryptosporidia in the Caco-2 cell line. AB - We used the spontaneously differentiated human intestinal epithelial cell line Caco-2 to develop an in vitro model of Cryptosporidium sp. infection. The mean cell infection rate was 3% +/- 2%. Asexual stages of cryptosporidia were observed on day 2 postinoculation. Transmission electron microscopy showed the presence of macrogametes at day 5. This cell line appears to be suited to the study of the mechanisms by which biological agents inhibit both sexual and asexual development of cryptosporidia. PMID- 1937822 TI - Stimulation of monokine production by lipoteichoic acids. AB - Lipoteichoic acids (LTAs) isolated from bacterial species, including Staphylococcus aureus, Streptococcus pyogenes A, Enterococcus faecalis, Streptococcus pneumoniae, and Listeria monocytogenes, were tested for their ability to stimulate the production of interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha in cultured human monocytes. LTAs from S. aureus and S. pneumoniae failed to induce monokine production when applied in the concentration range of 0.05 to 5.0 micrograms/ml. However, LTAs from several enterococcal species (0.5 to 5 micrograms/ml) induced the release of all three monokines at levels similar to those observed after lipopolysaccharide stimulation. The kinetics of IL-1 beta and tumor necrosis factor alpha release elicited by LTAs closely resembled those observed following lipopolysaccharide application. Cytokine production occurred in the presence of both fetal calf serum and autologous human serum. Hence, it was not dependent on complement activation and could not be suppressed by naturally occurring human antibodies. Deacylation caused the total loss of monocyte stimulatory capacity. Deacylated LTAs were unable to prevent monocyte activation by intact LTAs, so primary binding of these molecules probably does not involve a simple interaction of a membrane receptor with the hydrophilic portion of the molecule. The results identify some species of LTAs as inducers of monokine production in human monocytes. PMID- 1937823 TI - Transformation of Actinobacillus actinomycetemcomitans by electroporation, utilizing constructed shuttle plasmids. AB - Actinobacillus actinomycetemcomitans, a periodontal pathogen, has been strongly implicated in human periodontal disease. Advances in the molecular analysis of A. actinomycetemcomitans virulence factors have been limited due to the unavailability of systems for genetic transfer, transposon mutagenesis, and gene complementation. Slow progress can be traced almost exclusively to the lack of gene vector systems and methods for the introduction of DNA into A. actinomycetemcomitans. An electrotransformation system that allowed at least five strains of A. actinomycetemcomitans to be transformed with stable shuttle plasmids which efficiently replicated in both Escherichia coli and A. actinomycetemcomitans was developed. One plasmid, a potential shuttle vector designated pDL282, is 5.7 kb in size, has several unique restriction enzyme sites, and codes for resistance to spectinomycin and ampicillin. E. coli and A. actinomycetemcomitans were transformed with equal efficiencies of approximately 10(5) transformants per micrograms of DNA. Similar transformation efficiencies were obtained whether the plasmid DNA was isolated from A. actinomycetemcomitans or E. coli. In addition, frozen competent cells of A. actinomycetemcomitans yielded comparable efficiencies of transformation. Restriction enzyme analysis of pDL282 isolated after transformation confirmed the presence of intact donor plasmids. A plasmid isolated from A. pleuropneumoniae was also capable of transforming some isolates of A. actinomycetemcomitans, although generally at a lower frequency. The availability of these shuttle plasmids and an efficient transformation procedure should significantly facilitate the molecular analysis of virulence factors of A. actinomycetemcomitans. PMID- 1937824 TI - Production and characterization of neutralizing and nonneutralizing monoclonal antibodies against listeriolysin O. AB - Listeriolysin O (LLO) is a thiol-activated toxin secreted by the facultative intracellular pathogen Listeria monocytogenes. LLO is essential for the survival of the bacterium in the infected cell because it promotes lysis of the phagosome membrane and escape of the bacterium into the cytosol. LLO was used as an antigen for the production of nine monoclonal antibodies (MAbs) in mice. Three of these could inhibit the hemolytic activity of LLO. One of them inhibited binding of LLO to erythrocyte membranes. The two other antibodies blocked the activity of LLO at a step subsequent to membrane binding. Only two of the nine MAbs recognized three other purified SH-activated toxins, streptolysin O, alveolysin, and pneumolysin. Western blot (immunoblot) analysis of culture supernatants of Listeria ivanovii and Listeria seeligeri, two hemolytic species of the genus Listeria, revealed that two MAbs recognized ivanolysin and seeligerolysin. The latter was also recognized by two other MAbs, including one of the neutralizing antibodies. MAbs raised against a peptide, ECTG LAWEWWR, present in all thiol-activated toxins sequenced to date, recognized all toxins and were not neutralizing. Taken together, these results demonstrate the existence of regions important for hemolytic activity that are unique to hemolysins of the genus Listeria and show that regions outside the conserved peptide are important for activity of LLO. PMID- 1937825 TI - Inhibition of endotoxin-induced interleukin-6 production by synthetic lipid A partial structures in human peripheral blood mononuclear cells. AB - The effect of two synthetic lipid A partial structures, compound 406 (or LA-14 PP, identical in structure to the lipid A precursor, known as Ia or IVa) and compound 401 (lipid X), on the in vitro modulation of endotoxin (lipopolysaccharide)-induced interleukin-6 production by human blood mononuclear cells was investigated. Lipopolysaccharide of Salmonella abortus equi and synthetic Escherichia coli-type lipid A (compound 506, or LA-15-PP) had potent interleukin-6-inducing capacities. The maximum release of interleukin-6 was found after stimulation with 1 to 10 ng of lipopolysaccharide or 10 to 100 ng of synthetic E. coli-type lipid A per ml. Both synthetic lipid A partial structures (compounds 406 and 401) failed to induce interleukin-6 release. However, they inhibited lipopolysaccharide- or lipid A-induced interleukin-6 production in a dose-dependent manner. Inhibition was found not only in mononuclear cells but also in purified monocytes and was not due to a shift in the kinetics of cytokine production. Suppression was manifested in the early stage of interleukin-6 production. Inhibition was also found in the presence of recombinant gamma interferon, indicating that compound 406 and recombinant gamma interferon act in different, independent pathways. Our data, therefore, indicate that the inhibition of interleukin-6 production by lipid A partial structures may help elucidate the mechanism of interaction of the lipid A component of lipopolysaccharide with immune cells in the inflammatory reaction during gram negative infection. PMID- 1937826 TI - Specific binding of neoglycoproteins to Toxoplasma gondii tachyzoites. AB - Several studies have shown that protozoa bind to glycoproteins or neoglycoproteins. Here we report that Toxoplasma gondii binds strongly to bovine serum albumin-glucosamide. The binding was rapid, time dependent, partially reversible, saturable, and specific. Scatchard analysis showed about 40,000 molecules of bovine serum albumin-glucosamide per toxoplasma cell. The apparent dissociation constant was found to be 4.46 x 10(-8) M. PMID- 1937827 TI - Effects of macrophage colony-stimulating factor on reduction of viable bacteria and survival of mice during Listeria monocytogenes infection: characteristics of monocyte subpopulations. AB - Mice could well tolerate infection with a lethal dose of Listeria monocytogenes after intraperitoneal preinjections with 250 micrograms of macrophage colony stimulating factor (M-CSF) per kg of body weight for 5 days. The characteristic changes in the surface markers (Mac-1, LFA-1, and F4/80) of peripheral monocytes were also investigated in order to analyze the mechanism of protection by M-CSF. This investigation shows the excellent effect of intraperitoneal preinjections of M-CSF on the reduction of viable Listeria organisms and the improvement of survival after an intravenous Listeria infection. PMID- 1937828 TI - Role of the galactose lectin of Entamoeba histolytica in adherence-dependent killing of mammalian cells. AB - Entamoeba histolytica extracellular killing of host cells is contact dependent. Adherence to human colonic epithelial cells and mucins is mediated by a galactose specific lectin. The effect on cytotoxicity of a panel of monoclonal antibodies (MAb) directed against the galactose lectin was tested. As expected, those MAb which inhibited adherence also decreased cytotoxicity. However, one antilectin MAb blocked cytotoxicity after adherence had occurred, indicating that the lectin has a role in cell killing that is distinct from its adherence function. PMID- 1937829 TI - Gamma interferon-activated human macrophages and Toxoplasma gondii, Chlamydia psittaci, and Leishmania donovani: antimicrobial role of limiting intracellular iron. AB - Iron-saturated transferrin did not reverse the intracellular killing or inhibition of Toxoplasma gondii, Chlamydia psittaci, or Leishmania donovani by gamma interferon-activated human macrophages. Deferoxamine, an iron chelator, also did not impair replication within unstimulated macrophages. Limiting the availability of intracellular iron is an unlikely mechanism in human macrophage activity against these three diverse pathogens. PMID- 1937830 TI - Localization of translocating Escherichia coli, Proteus mirabilis, and Enterococcus faecalis within cecal and colonic tissues of monoassociated mice. AB - Normal bacteria can translocate (migrate) across an intact intestinal mucosa, but the anatomical site of bacterial translocation has not been defined. Gastrointestinal (GI) cross-sections were obtained from mice monoassociated with high cecal concentrations of Escherichia coli, Proteus mirabilis, or Enterococcus faecalis. As previously reported (C. L. Wells, R. P. Jechorek, and K. J. Gillingham, Arch. Surg. 126:247-252, 1991), these mice had viable translocating bacteria recovered from mesenteric lymph nodes and livers. No abnormal GI histology was noted. Immunofluorescence was used to localize GI bacteria, and similar observations were made with each of the three bacterial species. Smaller numbers (P less than 0.01) of bacteria were observed in stomach and small intestinal tissues than in cecal and colonic tissues, suggesting that the preferred site of tissue penetration for intestinal E. coli, P. mirabilis, and E. faecalis might be the cecum or colon as opposed to the stomach or small intestine. PMID- 1937831 TI - Expression of T-cell-associated serine proteinase 1 during murine Leishmania major infection correlates with susceptibility to disease. AB - The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis. PMID- 1937832 TI - Cytokine regulation of murine leishmaniasis: interleukin 4 is not sufficient to mediate progressive disease in resistant C57BL/6 mice. AB - Neutralization of interleukin 4 (IL-4) at the time of infection with Leishmania major allowed susceptible BALB/c mice to heal. Recombinant IL-4, however, had little effect on the course of L. major infection in resistant C57BL/6 mice, nor did coinfection with Nippostrongylus brasiliensis, despite marked elevation of endogenous IL-4 levels. PMID- 1937833 TI - Detection of Bordetella pertussis associated with the alveolar macrophages of children with human immunodeficiency virus infection. AB - In humans, infection with Bordetella pertussis is considered to be localized to an epithelial surface. However, an intracellular state in cultured cells and in the macrophages of infected animals has been shown. By using indirect immunofluorescence with a monoclonal antibody, it was found that 3 of 20 bronchoalveolar lavage specimens from children with human immunodeficiency virus infection had B. pertussis associated with pulmonary alveolar macrophages. None of the cultures from the patients grew B. pertussis. The B. pertussis appeared to be intracellular. PMID- 1937834 TI - Interleukin-1 administration to C3H/HeJ mice after but not prior to infection increases resistance to Salmonella typhimurium. AB - Interleukin-1 (IL-1) treatment of C3H/HeN and C3H/HeJ mice prior to infection with Salmonella typhimurium increased the survival fraction only in C3H/HeN mice. IL-1 administration after infection resulted in a significant increase in mean survival time in C3H/HeJ but not C3H/HeN mice. Bacterial growth in IL-1-treated C3H/HeJ mice was less than that in control mice. PMID- 1937835 TI - Properties of the B oligomer of pertussis toxin. AB - The B oligomer of pertussis toxin was purified from culture supernatants of Bordetella pertussis strains which do not secrete the S1 subunit. The purified B oligomer is devoid of toxicity for CHO cells and other in vivo properties of the toxin, such as leukocytosis and histamine sensitization, but it retains the abilities to agglutinate erythrocytes and to induce the proliferation of T lymphocytes. The B oligomer is also able to induce protective immunity in mice but is less potent than molecules containing the S1 subunit also. PMID- 1937837 TI - Etiologic role of Hafnia alvei in human diarrheal illness. PMID- 1937836 TI - A plasmid-encoded surface protein found in chronic-disease isolates of Coxiella burnetti. AB - The cbbE' gene codes for the E' protein of Coxiella burnetii and was detected in genomic DNA from all known human isolates of the biotzere strain but not in DNA from the other five strains of C. burnetti. The biotzere strain is strictly associated with chronic disease in humans. Extrinsic iodination of biotzere strain cells radiolabeled a 55-kDa protein which comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with the E' protein synthesized in vitro from recombinants containing the cbbE' gene. The 125I-labeled 55-kDa protein was immunoprecipitated with polyclonal anti-E' antiserum, confirming its identity as E'. Predicted secondary structure of the E' polypeptide shows six regions of beta-sheet structure and an alpha-helix near the C terminus with adequate lengths to span a membrane. The predicted hydropathy profile of E' is similar to profiles of known outer membrane proteins and corroborates the biochemical data, indicating that the protein is located in the outer membrane of C. burnetii. PMID- 1937838 TI - [Carbohydrates in parenteral nutrition solutions in pediatrics--a critical evaluation]. AB - Application of carbohydrates in pediatric infusion therapy has recently been limited to glucose and xylitol. Fructose and sorbitol, which formerly had been used widely as energy sources in parenteral nutrition, have meanwhile been banned in order to prevent fatal complications in patients with undiscovered hereditary disturbances in fructose metabolism. The aim of this review is to focus the attention on potential side effects and limitations of glucose administration in pediatric infusion therapy. With special regard to total parenteral nutrition in preterm infants, sufficient glucose conversion to N-acetylneuraminic acid and other carbohydrate building blocks of glycoproteins and gangliosides is to be placed in question. This might have consequences for normal brain development and can be considered a challenge for future research work in this field. PMID- 1937839 TI - [Parenterally administered medium-chain triglyceride-induced changes in carnitine metabolism]. AB - Medium-chain triglycerides are generally assumed to be metabolized independently of carnitine. The effects of infusing medium-chain triglycerides on plasma concentrations of carnitine derivatives and beta-hydroxybutyrate was studied in four healthy male adults. Glucose and amino acids were infused alone for three hours, then continued for another 5.5 hours together with a lipid emulsion containing only long-chain triglycerides or a mixture of medium-chain and long chain triglycerides (50:50; w/w). During the fat-free infusion, the concentration of free carnitine rose, while the level of acylcarnitines decreased. Infusion of the mixed emulsion over 5.5 hours reduced free carnitine to lower values (32.4 +/ 4.7 mumols/L) than long-chain triglycerides infusion (44.4 +/- 2.7 mumols/L). By contrast, the plasma concentrations of short-chain acylcarnitines (12.1 +/- 3.3 vs. 5.4 +/- 1.9 mumols/L; p less than 0.01) and of beta-hydroxybutyrate (93 +/- 32 vs. 47 +/- 14 mumols/L; p less than 0.01) became significantly higher with the mixed emulsion than with long-chain triglycerides. These findings suggest that oxidation of medium-chain fatty acids is to some extent carnitine-dependent, whether or not transport into mitochondria is carnitine-mediated. PMID- 1937840 TI - [Application and fixation systems in enteral nutrition]. AB - Enteral nutrition is becoming more convenient because of a lot of available different techniques. Tubes can be placed nasogastrically, nasoduodenally or nasojejunally, as bedside method controlled by X-ray or with the aid of an endoscope. If there is a risk of spontaneous removal, fixing with a stabilisation system is helpful. In cases where the tube should be hidden, a specially prepared plastic olive placed in the nostril can be used. All these methods are of interest for short and medium term enteral nutrition. For long term enteral nutrition, the percutaneous endoscopic gastrostomy, especially the so-called 'thread-pass-through' method is increasingly in use. All attempts to arrange a simpler method using direct punction techniques have failed up to now. The following paper gives a survey of different technical possibilities. PMID- 1937841 TI - [Approaches in parenteral nutrition]. AB - The central venous catheter, on the one hand, and the peripheral venous cannula, on the other hand, are available as fundamental access possibilities for parenteral nutrition. While the implantation of a central venous catheter is technically tiresome and subject to a complication rate up to 5%, the peripheral venous cannulization, in general, does not represent any technical problem. However, in case of peripheral venous access, due to the local venous compatibility, not only the duration of application is generally limited to 4-6 days, but the feeding of nutritious substances as such (excepting fat emulsions) is restricted, too. This means a limitation of the applicability in temporary and acute phases of a disease, as well as its application as a supplementary therapy in the event of oral or enteral nutrition. The advantage of the central venous parenteral nutrition refers to the possibility of a long-term high-doses, and thus to a complete parenteral, nutritional therapy. It is, however, subject to an aggravating rate of thrombotic (0.5-5%) and septic complication (3-6%), so that the indication and duration of application should be looked upon very closely and critically. The low-risk alternatives of a peripheral venous parenteral nutrition should be observed more closely. PMID- 1937842 TI - Comparison of different plateletpheresis systems. AB - Important criteria for assessing a cell separator are thrombocyte yield, separation efficiency, and purity of the thrombocyte concentrates. Based on a Multicentric Counting Study, in which 12 centers participated, we conclude that it is very difficult to compare the results of the various centers in regard to the separation efficiency. This is especially true for the comparison of different separation procedures. In Marburg we compared three different cell separators of the newest generation: COBE Spectra (n = 71), Fresenius AS-104 (n greater than 1100) and Fenwal CS-3000 TNX (n = 79). The COBE Spectra exhibited the best separation efficiency with the lowest leukocyte contamination (thrombocytes 4.3 x 10(11) (72.2%), leukocytes 0.5 x 10(7)) on the condition that the ACD-blood ratio did not differ more than -15% from the required algorithm. In order to reduce the risk to the donor, the system correspondingly reduces the donor's blood flow, resulting in a longer donation time (on the average 89-100 min). When the ACD ratio was reduced further, a considerable number of spontaneous and sometimes irreversible platelet aggregation occurred, increasing the risk of shortened survival through reduced platelet function. The AS-104 and the modified CS-3000 (TNX) had similar separation efficiencies (approx. 60%). While the platelet concentrates (PC) of the AS-104 almost reached the purity of that from the COBE Spectra, the leukocyte contamination of the CS-3000 PC's was still about four times as high. Other results published show that morphology, in vitro function and in-vivo survival of thrombocytes collected with the AS-104 are significantly better than those from the CS-3000.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937843 TI - Transfusion results of platelet concentrates using different cell separators. AB - 115 patients with bone marrow aplasia/hypoplasia received a total of 567 transfusions of fresh HLA-selected platelet concentrates at random from the AS 104 and CS-3000 and, whenever possible, from both separators using the same donor. By daily platelet counting pre and up to seven days post transfusion, the posttransfusional increments per 10(11) platelets transfused were calculated. Fresh platelets collected from the AS-104 showed comparable in vivo recovery at the first day post transfusion but significant better survival compared to those from the CS-3000. This is in line with in vitro studies published before, where we already reported on better in vitro function and morphology. Increased platelet yields and improval of the platelet survival of the PC's from the AS-104 should result in prolonged transfusion intervals. When additionally evaluating a limited number of PC's from the AS-104 stored in teflon bags up to five days before transfusion (n = 12), we did not get favorable results compared to PC's from the CS-3000 stored in polyolefine bags. As this seemed to be due to the geometry of the bags, it was consequently changed in the meantime. PMID- 1937844 TI - [The thrombin-antithrombin III complex ELISA test in diagnosis of surgery-induced blood coagulation activation]. AB - In addition to measuring the routine blood coagulation parameters (Quick, PTT, TT, AT III, Fibrinogen, PLT), the Thrombin-Antithrombin III Complex (TAT) Test was performed preoperatively on 20 patients treated because of nodular goiter in the euthyreoid state and ten patients with symptomatic cholecystolithiasis. While there were no changes in the routine blood coagulation parameters, significant alterations of the TAT occurred in both patient groups. This indicates that TAT makes operation-induced activation of the blood coagulation system, which is impossible by just measuring the routine blood coagulation parameters alone, detectable. PMID- 1937845 TI - Toxic effects of dental materials. AB - Dental materials and clinical accessories may potentially cause adverse reactions in dentists, auxiliaries or patients. The introduction of new dental materials and a general awareness of adverse effects has been accompanied by an increase in the number of complaints related to dental treatment and to occupational exposure. Resin-based materials with various monomers, used as restorative composite materials, orthodontic adhesives and appliances, prosthodontic resins and impression materials, have all been involved. Reactions to metals used in extra-oral appliances in orthodontics seem to be relatively frequent, but few reactions have been reported following the use of other alloy systems. Some reactions may be due to toxic or allergic effects, but some are unexplained. Adverse reactions to any substance will usually be detected first in a setting where the exposure is greatest. This also holds true for dentistry, where some of the adverse reactions may be due to lack of knowledge about the toxic, irritant and allergenic properties of dental materials. PMID- 1937846 TI - Primary failure of eruption: a case report. AB - The long-term effect of extracting infra-occluded (submerged) first permanent molars on the subsequent movement of the second permanent molars was studied in a member of a family with previously noted primary failure of tooth eruption. The case is described with the use of radiographs and diagrams and the conclusion reached that in some pathological conditions tooth movement takes place in an apical direction, an observation that may be termed 'paradoxical' tooth movement. PMID- 1937847 TI - Role of chlorhexidine in the management of dental caries. AB - Chlorhexidine has a role in the management of patients with a high level of disease, but it is not a universal panacea for caries control. This paper reviews the antibacterial activity and mode of action of this antiseptic and presents the evidence supporting its use in caries control. Current clinical applications are suggested and the methods of application described. PMID- 1937848 TI - Periodontal regeneration: myth or reality? AB - Recent scientific advances have enabled scientists to understand some of the basic biological events leading both to an accelerated and improved healing of many tissues. These advances are now being applied to periodontal wound healing. Previous studies have indicated that various oncogenes are sequences related to growth factors and, that when these sequences are altered, cellular phenotype and especially cellular proliferation is altered. Data are presented using various human cell lines, including a c-myc-transfected periodontal ligament (PDL) cell line, which delineate the relationship between oncogenes, mRNA oncogene transcripts and polypeptide growth factors as inducers of cell phenotypic alterations, including adhesion, migration and proliferation. The polypeptide growth factors are a unique class of molecules that regulate cell phenotype both in vitro and in vivo. These demonstrable phenotypic conversions have indicated that such factors will play an important role in hard-soft tissue repair. Additionally, new data suggest that older PDL cells are not responsive to polypeptide stimulation; both the migratory and proliferative responses are diminished. A unique growth factor has been isolated and sequenced, which when applied to older PDL cells will reverse this refractory phenotype. These recent studies are extensively reviewed with emphasis and conclusions based on growth factor-induced periodontal regeneration. These studies stress the undeniable role that these novel approaches will have in future chairside periodontal practice. PMID- 1937849 TI - Delivery of oral health care to the elderly patient. AB - This paper, delivered at the 1990 FDI Singapore Congress, reports the results of studies performed by a Working Group, appointed by the Commission on Dental Education and Practice, to study the delivery of oral health care to the elderly patient. The teaching of gerodontology was also included in the group's remit. The problems of the widely differing oral health care needs of the elderly in different societies around the world are considered and recommendations made. PMID- 1937850 TI - Detection and management of the high risk periodontal patient. AB - Periodontal diseases and patients at risk for progression of disease can be diagnosed on the basis of age, previous episodes of periodontal disease and loss of attachment, as detected by periodontal probing and radiographic evaluation. For early onset periodontitis, family history may be important. Microbiological evaluations are excellent determinants of disease and also appear to be probable predictors of 'at risk' patients. Reliable tests, including chairside tests, are available for the three most probable pathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia. Biochemical changes, although associated with various disease states, are not yet readily measurable at the chairside, with the exception of one test that measures aspartate aminotransferase and shows promise as a detector and predictor of periodontal disease. The diagnosis and 'at risk' prediction of periodontal disease is based on a number of criteria, some of which are highly reliable and others whose reliability is either probable or unclear. These criteria are reviewed with emphasis on those that may be indicative of the patient at high risk of developing periodontal disease or progressing to a more severe form of disease. PMID- 1937851 TI - Rebuilding the ruins: dental services and manpower in Cambodia. AB - Between 1975 and 1979 Cambodia suffered a massive destruction of its social structures under the Khmer Rouge. The dental profession was almost annihilated and the dental school in Phnom Penh stripped bare. Dental training has now begun again and the long process of restoration is in progress. The ratio of dentists to the population is still pitifully low and public services are concentrated in Phnom Penh and in provincial towns. Traditional dentists provide the only accessible dental care in many places. A primary oral health care system has yet to be developed. PMID- 1937852 TI - The new Spanish curriculum: reasons for change. AB - To summarize it can be stated that: The dependence of dental science on medicine in Spain has not been in any way advantageous to the profession, the practice of dentistry or the oral health of the population. Today's teaching must change if Spain is to face up to the enormous challenges of the future, including new trends in demand, the right to health and the decrease of the professional's standard of living. In future it will be necessary to include new curricular parameters, such as the organization of work, prevention and behavioural sciences, etc., with the objective of being able to provide the population with improved and more accessible services. It is necessary to reflect upon the position as regards technology, so as to be able to optimize its utilization at each appropriate level and avoid excessive dependence on industry. The new curriculum has been based on an increased amount of teaching of the basic and medical sciences, an earlier integration of the students into the clinic, a closer relationship with the community, and finally, a more integrated approach to, and methodology in, all clinical work. In Spain, both the State and the universities have made an enormous effort to bring the teaching of dental science up to date by seeking its equivalence and harmony with that of the EEC. This effort, owing to the special circumstances within Spain, has made the acceptance and extension of a profound philosophical, academic and professional change necessary. PMID- 1937853 TI - Periodontal epidemiology in Italy by CPITN. PMID- 1937854 TI - Care of organ donors. AB - In summary, anesthesiologists play a pivotal role in maintaining adequate organ function in the donor. Anesthesiologists are responsible for integrating the needs of all transplant services involved in donor organ retrieval. In addition, anesthesiologists can play critical roles in expediting preparation of the patient for surgery, and they can lend emotional support to operating room personnel during the surgery. The care of the organ donor is really the care of several patients--the donor and the fortunate recipients of the donated organs- and can afford great personal satisfaction. PMID- 1937855 TI - Multiviscera and pancreas transplantation. PMID- 1937856 TI - Special considerations for transplantation in children. PMID- 1937857 TI - Kidney transplantation. AB - Kidney transplantation in adults, infants, and children is a safe and effective treatment of ESRD. In 1990, for all patients with irreversible ESRD, transplantation is the preferred treatment over dialysis. With careful perioperative management by the surgeon and anesthesiologist, the morbidity is very low. Thus increased use of grafts from living donors appears warranted. Continued refinements and advances in immunosuppression should result in even better long-term graft and patient survival. PMID- 1937859 TI - Liver transplantation. PMID- 1937858 TI - Heart transplantation. PMID- 1937861 TI - Cellular and molecular networks in clinical immunology and allergy. 18th symposium, Collegium Internationale Allergologicum. Funchal, Madeira,September 22 26, 1990. Proceedings. PMID- 1937860 TI - Lung transplantation. PMID- 1937862 TI - Are allergen-specific IgG mainly IgG anti-IgE autoantibodies? AB - A large proportion of specific IgE occurred in immune complexes with anti-IgE autoantibodies in sera from nonhyposensitized allergic patients. These autoantibodies were misinterpreted as 'specific IgG' in different immunoassays such as dot immunoassays and the radioallergosorbent test (RAST), leading to overestimation of specific IgG. Purified immune complexes contained even more IgG than IgE antibodies. Heating of the complexes liberated specific IgE, producing an upwards RAST class shift. Thus anti-IgE autoantibodies are hiding the specific IgE, which is thereby underestimated. It is not known whether the hiding anti-IgE autoantibodies are also effectively neutralizing circulating or cell-bound IgE and might represent the actual blocking antibody. PMID- 1937863 TI - Carl Prausnitz Memorial Lecture. Suppression of antibody responses by chemically modified antigens. AB - Some of the studies employing nonantigenic, nonallergenic and tolerogenic derivatives of antigens and allergens, synthesized by coupling onto them an optimal number (n) of molecules of monomethoxy-polyethylene glycol (mPEG), are briefly reviewed. Administration of antigen (mPEG)n conjugates into mice resulted in specific immunosuppression, which was mediated by antigen-specific suppressor T (Ts) cells and by suppressor factor(s) (TsF) produced by these cells. These Ts cells were cloned and shown to be Thy-1.2+, CD3+, CD4-, CD5-, CD8+, and expressed the alpha beta heterodimer of conventional T cell receptors (TCR). The TsF had the functional activity of Ts cells and possessed at least one epitope related to the alpha-chain of TCR. The results of clinical trials of mPEG conjugates of common allergens are briefly referred to; it is suggested that the time is opportune for the evaluation of the therapeutic efficacy of mPEG conjugates of pure allergens which can be synthesized on an industrial scale by recombinant DNA technology. Finally, possible applications of tolerogenic mPEG conjugates of xenogeneic monoclonal antibodies, immunotoxins and immunogenic recombinant lymphokines to the development of immunotherapeutic strategies in oncology, transplantation, autoimmunity and acquired immunodeficiency syndrome are discussed. PMID- 1937864 TI - In vitro development and functions of human mast cells. AB - A long-term co-culture of mononuclear cells of human umbilical cord blood with mouse embryo-derived 3T3 fibroblasts resulted in the development of human mast cells. These mast cells are morphologically and functionally mature cells, containing 1.4-2.8 micrograms histamine per 10(6) cells and bear approximately 10(5) Fc epsilon RI per cell. The mast cells sensitized with human IgE released histamine upon challenge with anti-IgE. Electron-microscopic analysis of the cells showed that these cells were mature human mast cells, and clearly different from basophilic granulocytes. Most of the mast cells contained some granules with regular crystalline arrays and both tryptase and chymase, resembling human skin mast cells. When mononuclear cells of cord blood were seeded in a millicell insert which was placed on 3T3 fibroblasts monolayer, the number of mast cells developed in the millicell inserts was comparable to those developed in the co culture of the same cord blood cells with 3T3 fibroblasts. Recent observations that mast cells developed in the presence of concentrated culture supernatants of 3T3 fibroblasts without fibroblasts feeder layers, confirmed that soluble factors released from 3T3 fibroblasts are essential and sufficient for the differentiation of human mast cell progenitors in vitro. Analysis of functional characteristics of cultured mast cells revealed that they respond to anti-IgE, Ca2+ ionophore A23187 and substance P for histamine release, but failed to respond to compound 48/80 and FMLP. Upon anti-IgE challenge, sensitized mast cells generated approximately 80 ng PGD2 per 10(6) cells, and approximately 50 ng of LTC4 per 10(6) cells but no detectable generation of LTB4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937865 TI - Control of eosinophilia. AB - Experiments in vitro have suggested that IL5 is a late-acting factor in eosinophil production, and that other factors such as IL3, G-CSF and GM-CSF are required for the production of committed eosinophil progenitors. Furthermore, work in vitro indicates that in addition to IL5, both IL3 and GM-CSF are capable of stimulating eosinophil differentiation. Thus, there would appear to be both considerable redundancy in cytokine actions in eosinophilia as well as a complex network of cytokine activities to induce eosinophilia. Experiments in vivo, however, suggest a less complicated control mechanism, dominated by IL5. PMID- 1937867 TI - Platelet-activating factor modulates interleukin-6 production by mouse fibroblasts. AB - We compared the effects of platelet-activating factor (PAF), interleukin-1 beta (IL-1 beta) and polyriboinositic-polyribocytidylic acid (poly-I:C) on IL-6 production by confluent L929 mouse fibroblasts. At concentrations above 1 microM, PAF dose-dependently enhanced IL-6 production; at 5 microM PAF this increase (72.7 +/- 19.9 U/ml) was higher than that evoked by 100 U/ml IL-1 beta (5.7 +/- 0.4 U/ml) or 50 micrograms/ml poly-I:C (39.3 +/- 6.7 U/ml). The IL-6 production induced by 5 microM PAF was not inhibited by addition of the specific PAF antagonist BN 52021 (10 microM) to the incubation medium. These results demonstrate that, as this is the case for IL-1, PAF also modulates IL-6 production. PMID- 1937866 TI - Structural cell-derived cytokines in allergic inflammation. AB - Based on observations of fluctuations in progenitors for inflammatory cells during allergic responses, we have proposed that a primary determinant of allergic inflammation involves microenvironmental influences on hemopoietic cell differentiation and phenotype; in addition, as a corollary of this, inflammatory cell burden is proposed as an important indicator of the severity and pattern of the inflammatory process in allergy. The studies outlined here focus on the effects of epithelial-cell- and fibroblast-derived cytokines on granulocytic and monocytic cell differentiation and activation in models involving allergic reactions in the upper and lower airways. Pure cultures of nasal or bronchial epithelial cells or fibroblasts are observed to give rise to cytokines important in inducing the differentiation of basophils, eosinophils, neutrophils and monocyte/macrophages. Gene expression, production and secretion of granulocyte/macrophage-colony-stimulating factor, interleukin-6 (IL-6) and IL-8 can be demonstrated in vitro and in vivo. Up-regulation of gene expression and production of these cytokines, which are important in inducing basophil, eosinophil and neutrophil/macrophage differentiation in several assays, is seen with IL-1 and the neuropeptide substance P; conversely, inhibition of cytokine production by structural cells is observed after pretreatment with corticosteroids in vitro, paralleling in vivo effects. Other modulatory effects also examined include: antiallergic compounds, which may affect posttranscriptional events in cytokine production, and heavy metal ions, which can also induce changes in gene expression. Structural-cell-derived extracellular matrices appear also to be important both in mast cell differentiation and in macrophage cytokine gene expression, both of which potentially feedback upon chronic allergic inflammatory processes, leading to their perpetuation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937868 TI - Interleukin-5 mRNA in mucosal bronchial biopsies from asthmatic subjects. AB - Using in situ hybridization, we have investigated the expression of interleukin-5 (IL-5) mRNA in bronchial biopsies from asthmatics (n = 10) and controls (n = 9). The number of IL-5-nRNA-positive cells were compared with the number of CD25+ and EG2+ cells and total eosinophil counts. Specific hybridization signals for IL-5 mRNA were demonstrated in 6 out of the 10 asthmatic subjects but in none of the controls. The 6 IL-5-mRNA-positive asthmatics tended to have more severe disease and showed a significant increase in the degree of infiltration of the bronchial mucosa by activated T lymphocytes and eosinophils. PMID- 1937869 TI - T-cell-dependent accumulation of eosinophils in the lung and its inhibition by monoclonal anti-interleukin-5. AB - The transnasal administration of an extract of the parasite Ascaris suum to C57BL/6 mice for 3 weeks produced marked eosinophilia in the bronchoalveolar lavage (BAL) fluid. The oral administration of ciclosporin significantly suppressed the pulmonary eosinophilia. Athymic C57BL/6-nu/nu mice failed to develop pulmonary eosinophilia. These data indicate that the pulmonary eosinophilia caused by this parasite extract is T-cell-dependent. Genetically mast-cell-deficient (WB x C57BL/6) F1-W/Wv (W/Wv) mice developed marked eosinophilia in the BAL, which shows that mast cells are not necessary in the formation of lung eosinophilia in this model. Monoclonal antimurine interleukin-5 injected intraperitoneally clearly inhibited the infiltration of eosinophils in the lung, suggesting that T-cell-derived interleukin-5 is essential. PMID- 1937870 TI - Identification of a spleen cell-derived factor that inhibits sensitization of murine peritoneal mast cells as interferon-gamma. AB - We present evidence that a spleen cell-derived factor that inhibits the sensitization of mouse peritoneal mast cells is IFN gamma. Conditioned medium (CM) from Con A-activated mouse spleen cells and recombinant MuIFN gamma both inhibited antigen-induced 5-HT release from peritoneal mast cells when added at the sensitization stage, but were without effect on presensitized cells. Both preparations were active at dilutions corresponding to similar levels of IFN activity (1-10 units/ml). The inhibitory activity of CM was blocked by a rat monoclonal MuIFN gamma-neutralizing antibody, thus confirming that IFN gamma was the active molecule. PMID- 1937871 TI - Interleukin-4 induced IgE and IgG4 secretion by B cells from atopic dermatitis patients. AB - Peripheral blood mononuclear cells from 8 normals and 8 patients with atopic dermatitis (AD) were cultured with recombinant interleukin-4 (IL-4) and the IgE and IgG subclass levels in the culture supernatants measured by radioimmunoassays. IL-4 induced IgE and IgG4 secretion by B cells from both normals and AD patients whereas it has no consistent effect on IgG1, IgG2 and IgG3 secretion. The IL-4 dose response was similar for IgE and IgG4 secretion by cells from both normals and AD patients. On the average, the patients' cells secreted more IgE and less IgG4 than the cells from normals, but because of a large variation, the differences were not significant. However, the ratio of IgG4:IgE secretion was significantly greater for normals than AD patients (mean +/- SEM 7.1 +/- 1.6:1 vs. 1.5 +/- 0.4:1; p less than 0.01). The data demonstrate that IL-4 induces IgE and IgG4 secretion by B cells from both normals and AD patients and suggest that the IL-4 induced switch from IgM to IgG4 or IgE secretion may proceed preferentially to IgE in AD patients as compared to normals. PMID- 1937872 TI - Interleukin-4 gene expression and IgE responsiveness. AB - Interleukin-4 (IL-4) gene expression by stimulation with concanavalin A (Con A) in murine spleen cells was examined. The amount of IL-4 mRNA induced by Con A was greatest in spleen cells obtained from IgE high responder strains of mice. A trace amount of IL-4 mRNA was induced in spleen cells from IgE low responder (SJL) mice. The amount of IL-4 mRNA induced in spleen cells from an IgE intermediate responder (C57BL/6) was smaller than that from high responders, but significantly greater than that from low responders. Spleen cells from IgE nonresponders (SJA/9) developed only a negligible amount of IL-4 mRNA. IL-4 mRNA was detected in human peripheral blood mononuclear cells (PBMC) stimulated with Con A. The IL-4 gene expression seemed to be greater in PBMC obtained from highly atopic patients and was decreased in PBMC from individuals showing hypo-IgE immunoglobulinemia (less than 10 IU/ml). The results obtained in the present study may indicate that high and low IgE responder traits are determined depending on their levels of IL-4 mRNA expression. PMID- 1937873 TI - T lymphocytes and their products in atopic allergy and asthma. AB - Various cells are associated with inflammatory events characteristic of atopic allergy and asthma. As well as T cells and eosinophils, mast cells, basophils, mononuclear phagocytes and platelets have all to be considered particularly as their mediators have potential for contributing directly to the features of bronchial asthma. Nevertheless, mast cell/T lymphocyte/eosinophil interactions may be of particular significance. For instance, the acute symptoms of allergy and asthma such as sneezing, bronchospasm and hives are believed to be largely the result of mediator release from mast cells whereas chronic symptoms (the result of allergic inflammation) can be explained on the basis of eosinophil mediated tissue damage. Allergen is recognized directly by T cells. Specialized T cell subsets, possibly the Th2 equivalent, predominate in allergy and elaborate IL-4 (an essential co-factor for IgE production) and IL-5 which brings about terminal differentiation and activation of the eosinophil. Basic proteins derived from the crystalloid granule together with PAF and leukotrienes produce chronic wheeze, bronchial irritability, and might also be involved in permanent nasal blockage in chronic rhinitis. This general hypothesis is continually being tested. It is clearly important to identify precise molecular targets in allergy and asthma in order to construct therapeutic strategies. PMID- 1937874 TI - Atopic eczema, Langerhans cells and allergy. AB - While the pathomechanisms of respiratory atopy are rather well established, the role of IgE-mediated hypersensitivity in the elicitation and maintenance of eczematous skin lesions in atopic eczema is still controversial. Few diseases are characterized by an equally elevated production of IgE antibodies as atopic eczema. Many authors, however, regard this only as epiphenomenon. On the other hand, there is clearcut clinical evidence for exogenous elicitation of atopic eczema by contact with aero or food allergens. A variety of hypotheses may help to explain the participation of IgE antibodies in the induction of eczema: vasoactive mediators secreted by skin mast cells or basophils after allergen contact may produce itch, contact urticaria or a 'late-phase-reaction' with consequent eczematous skin changes further maintained by scratch responses. Recent investigations stress a possible role of Langerhans cells in the epidermis with a low affinity receptor for IgE with possible function for antigen presentation, mediator release or regulatory interactions. Certain cytokines such as interleukin-4 or gamma-interferon are able to enhance the expression of the IgE-receptor on the surface of Langerhans cells. IL-4 and gamma-interferon act synergistically in this respect on Langerhans cells, contrary to B cells. Furthermore lymphocytes may act directly via certain cytokines (e.g. histamine releasing factor, chemotactic factors etc.) on mast cells or eosinophil granulocytes in a proinflammatory sense. Eosinophils seem also to be involved in the inflammatory response in atopic eczema by releasing products such as major basic protein (MBP) or eosinophil cationic protein (ECP) which has been found to be elevated in severe atopic eczema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937875 TI - Biographical sketch of Dr. Klaus Rother. PMID- 1937876 TI - Allergic inflammation and its pharmacological modulation in asthma. AB - While most asthma occurs in association with atopy, the relationship of this to clinical expression of the disease is not clearly understood. Allergen provocation causes an immediate bronchoconstriction (early asthmatic reaction) due to the release of mast-cell-derived histamine, prostaglandin D2 and leukotriene C4. The late reaction and attendent increase in bronchial responsiveness are associated with eosinophil influx, activation and mediator secretion, resulting in mucosal swelling in addition to smooth muscle contraction. Endobronchial biopsy and broncho-alveolar lavage have provided compelling evidence that both mast cells and eosinophils contribute to disordered airway function in 'clinical' asthma and that these cells are under the control of T lymphocytes. Topical corticosteroids which produce beneficial clinical effects probably do so by inhibiting those factors that maintain mast cell and eosinophil populations and their enhanced activation. The most likely contenders for these regulatory functions are the cytokines, particularly interleukin-3, -4 and -5. PMID- 1937877 TI - Mast cell heterogeneity: protein composition, biosynthesis and mRNA characterization. AB - Proteins of rat peritoneal mast cells (PMC), rat intestinal mast cells (IMMC) and human skin mast cells (SMC) were compared by two-dimensional electrophoresis. PMC and IMMC had many similarities in distribution of their neutral/acidic proteins but marked differences in the more abundant, granule-associated basic proteins. SMC proteins showed a unique distribution. Distributions of the products of in vitro translation of PMC and IMMC RNA were different from those of proteins isolated directly from these cells which, together with results of pulse-chase labelling experiments, shows evidence for processing of certain mast cell proteins including rat mast cell proteases I and II. PMID- 1937878 TI - Mucosal exudation in respiratory defence: neural or non-neural control? AB - In human and animal airways, mucosal exudation of unfiltered plasma occurs promptly in response to inflammatory provocations (allergen, occupational factors, mediators). Mucosal exudation is distinctly an increase in outward permeability of vascular-mucosal barriers and it leaves the epithelial lining intact. Through its volume, its proteins including immunoglobulins, its enzyme systems and its newly generated peptides, the plasma exudate constitutes a comprehensive first-line mucosal defence. In rodent, but not in human airways, tachykinin neuropeptides have a demonstrated capacity to produce mucosal exudation. PMID- 1937879 TI - Inflammatory processes in asthma. AB - Bronchial inflammation is a characteristic of asthma, but, although postmortem and rare bronchoscopic studies had been performed, it is only after 1980 that many experiments were done. Electron microscopy, immunohistochemistry and molecular biology have enhanced our knowledge. As bronchial biopsies and bronchoalveolar lavage present drawbacks, it is favorable to combine both to obtain the best insights into inflammation. The epithelium is rarely intact in asthmatic patients, the cells being both 'fragile' and activated. Eosinophil inflammation is highly important and likely involved in the damage of the epithelium and submucosa. Airway macrophages and monocytes are present in greater amounts and are activated in the bronchi, and they are certainly involved in the pathogenesis of asthma. Mast cells are activated and some emphasis has been put on lymphocytes. Therefore, asthma appears to be a desquamative bronchitis with mixed cell infiltrate. PMID- 1937880 TI - Complement in inflammation: induction of nephritides and progress to chronicity. AB - The C5b-9 complex has a dual role as a factor involved in the initiation of nephritides and in the progress to chronicity and sclerosis. The unique pathophysiology of the membrane attack complex, distinct from other mediators, is its independence from specific receptors. It inserted in any membrane lipid bilayer tested so far. PMID- 1937881 TI - Functional heterogeneity of human mast cells. PMID- 1937882 TI - Possible role of macrophages in allergic rhinitis. AB - Mononuclear phagocytes have been investigated in biopsies taken from the nasal mucosa and in epithelial cell samples from 22 grass-pollen-allergic subjects before season, after allergen challenge and during season by means of immunohistochemistry and electron microscopy. The cells were positive for CD68/EBM11 and HLA-DR, but failed to react with CD1 and CD23/BB10. The cells increased in number during season as well as after allergen challenge, especially in the upper part of the mucosa. Heteromorphy of macrophages, as seen by transmission electron microscopy, confirmed the presence of diverse macrophage subpopulations in the nasal mucosa of allergic subjects. Using brush sampling techniques, CD68-positive and HLA-DR-positive cells significantly increased in epithelial cell samples 4-8 h after allergen challenge, indicating a central role of these cells not only in antigen processing but also in late phase reactions of allergic rhinitis. PMID- 1937883 TI - Evaluation of immune parameters in HIV+ subjects reporting adverse reactions to sulfamethoxazole. AB - Trimethoprim-sulfamethoxazole (TMP-SMX) is frequently used in human immunodeficiency virus (HIV)-infected patients (HIV+) for treatment or prophylaxis of Pneumocystis carinii pneumonia (PCP). Up to 80% of those patients report adverse reactions to that drug combination. To test the hypothesis that these reactions are immunologically mediated, we quantitated specific IgG and IgE SMX-human serum albumin (HSA) antibodies and immune complexes (IC) in HIV+ patients and in HIV controls. Patients with mild HIV disease had elevated specific SMX-HSA IgG and IC levels compared with those having severe disease or with controls. Conversely, patients with severe HIV disease had statistically elevated levels of specific IgE when compared with patients having milder disease or with controls. There were no differences in either specific antibody or IC levels between patients reporting adverse reactions and those who did not. Results suggest that there are increased levels of SMX-HSA-specific antibodies in some HIV+ patients. The presence of these antibodies appears to be related to severity of disease, rather than clinically significant drug sensitivity. PMID- 1937884 TI - T cells and asthma. II. Regulation of the eosinophilia of asthma by T cell cytokines. AB - Peripheral blood eosinophilia of both allergic and nonallergic asthmatics was found to correlate with blood T cell activation and lymphokine production. A close correlation was shown between the increase of IL-2 receptor expressing T cells and the number of eosinophils. These in vivo activated T cells spontaneously released factors that prolonged eosinophil survival in vitro. The T cell derived lymphokines IL-5, GM-CSF and IL-3 were demonstrated to be responsible for prolonged eosinophil survival in vitro, and were identified in T cell supernatants and sera from asthmatics. In summary, T cell derived cytokines play an important regulatory function towards eosinophils in asthma. PMID- 1937885 TI - Platelet aggregation in allergic reactions. AB - The platelet aggregation in the presence of 4 aggregation inducers was studied in 63 allergic patients, consisting of atopic and non-atopic asthmatics and aspirin sensitive subjects, before and after inhalation tests or in vitro incubation with allergen. Basal platelet aggregation was decreased in 43% of the atopic patients for adrenaline and also in a smaller percentage for other agonists. A decreased aggregation was also observed in 3 out of 6 nonatopic patients and in aspirin sensitive patients. In vivo or in vitro provocation tests decreased aggregation in some additional patients. These results point out to a compromise of platelets in allergic mechanisms. PMID- 1937886 TI - New antiasthmatic drugs from traditional medicine? AB - Several plants are used in traditional medicine for the treatment of bronchial asthma. We are trying to identify the active compound(s) and their mode of action. For the isolation and identification of the active principles, different chromatographic methods, HPLC, MPLC, elementary analysis, UV, mass, 1H- and 13C NMR spectroscopy are used. Whole plant extracts, fractionated extracts and pure compounds are tested in the following pharmacological systems: cyclooxygenase and lipoxygenase pathway of arachidonic acid metabolism, bronchial obstruction of guinea pigs after inhalation of allergens, platelet-activating factor (PAF), histamine or acetylcholine, PAF-induced bronchial hyperreactivity of guinea pigs, histamine release, chemoluminescence and chemotaxis of human polymorphonuclear leukocytes as well as thromboxane biosynthesis of human platelets. As active compounds in onion extracts, thiosulfinates and cepaenes could be identified. They exert a wide spectrum of pharmacologic activities, both in vitro and in vivo. Tetragalloyl quinic acid from Galphimia glauca, suppressed allergen- and PAF-induced bronchial obstruction, PAF-induced bronchial hyperreactivity (5 mg/kg orally) in vivo and thromboxane biosynthesis in vitro. Hitherto unknown alkaloids from Adhatoda vasica showed pronounced protection against allergen-induced bronchial obstruction in guinea pigs (10 mg/ml aerosol). Androsin from Picrorhiza kurroa prevented allergen- and PAF-induced bronchial obstruction (10 mg/kg orally; 0.5 mg inhalative). Histamine release in vitro was inhibited by other compounds of the plant extract yet to be identified. Pharmacological effects of plant extracts and pure compounds in man are under investigation. PMID- 1937887 TI - Airway inflammation and atopic asthma: a comparative bronchoscopic investigation. AB - Flexible fibre-optic bronchoscopy under local anaesthesia has been used to investigate the cellular airway events in atopic asthma. The findings have been compared to those from atopic individuals without asthma and non-atopic healthy controls, in an attempt to discern those changes relevant to clinical disease expression. Immunohistochemical and electron-microscopic analyses of airway biopsies identified that an atopic diathesis is associated with tissue eosinophil infiltration and mast cell degranulation. The eosinophilia was greatest in those atopic individuals with asthma. Flow-cytometric analysis of airway lavage revealed significantly enhanced T lymphocyte activation in clinical asthma. These findings are consistent with the hypothesis that T lymphocyte activation, through cytokine release, amplifies the tissue eosinophilia in asthma and that this combination is associated with clinical disease expression. PMID- 1937888 TI - Exercise-induced asthma in adolescent gym class population. AB - The prevalence of exercise-induced asthma (EIA) was determined in a population of 12- and 13-year-old schoolchildren whose parents returned a questionnaire regarding a previous diagnosis of asthma, recent asthmatic symptoms and symptoms of allergic rhinitis. EIA was defined as a greater than 15% fall in peak expiratory flow rate (PEFR) following 6 min of free running in a gymnasium. Among the 201 children studied, 18 (8.9%) demonstrated EIA. Of 21 children with symptomatic asthma in the 6 months prior to study, 9 (43%) developed EIA compared to none of 6 children with asymptomatic asthma (p less than 0.0001). Among 48 children with a history of allergic rhinitis alone, 7 (14.6%) demonstrated EIA. The mean postexercise changes in PEFR were 14.9% for 16 children with both asthma and allergic rhinitis, 6.4% among 48 children with allergic rhinitis only, and 1.8% among 125 normal children. Recent symptoms of asthma and a history of allergic rhinitis appeared to be risk factors for EIA. EIA was readily demonstrated in a gym class setting; the use of such screening may facilitate its diagnosis and treatment. PMID- 1937889 TI - Ragweed-specific IgA in nasal lavage fluid of ragweed-sensitive allergic rhinitis patients: increase during the pollen season. AB - Because the secretions of asthma and rhinitis contain toxic eosinophil granule proteins and because secretory IgA is the most potent immunoglobulin stimulus for eosinophil degranulation, we measured eosinophil-derived neurotoxin and ragweed specific IgA and IgE antibodies in nasal lavage before and during the ragweed pollen season in 44 hay fever patients. We found IgA antibody in nanogram/milliliter concentrations before the season and rising 20-fold by the end of the season. IgE antibody was present in picogram/milliliter concentrations and did not change. Eosinophils and eosinophil-derived neurotoxin also increased. We conclude that IgA is the predominant antibody in allergic nasal secretions and increases with allergen exposure. The hypothesis that secretory IgA antibody allergen complexes contributes to allergic inflammation by stimulating eosinophil degranulation warrants further study. PMID- 1937890 TI - Comparison of dermal and systemic application of glucocorticoids on the RM 3/1+ macrophage in human blood. AB - Dermal administration of either hydrocortisone or fluprednidene to healthy skin causes only a weak and short-lasting increase of the proportion of the anti inflammatory macrophage RM 3/1 in the blood compared to the effect of the systemic application of glucocorticoids on this cell subtype. On the other hand, a rather permanent increase of these macrophages could be observed in untreated patients suffering from certain skin diseases, e.g. urticaria, atopic dermatitis, psoriasis. PMID- 1937891 TI - Late phase increase of thrombin-like proteinase, protein, leukocytes in bronchoalveolar lavage (BAL) fluid and chemiluminescence of BAL after ovalbumin aerosol inhalation by actively immunized rats. AB - A thrombin-like proteinase (THROLP) was detected colorimetrically as the main proteolytic activity (PROA) in bronchoalveolar lavage fluid (BALF) 4 and 24 h after ovalbumin aerosol (OVA) challenge of actively immunized rats. Other proinflammatory parameters increased also significantly in BALF, like chemiluminescence of leukocytes (1 h), protein and cell number (24 h after challenge). In parallel, increased bronchoconstrictions against 5-HT aerosols are detected 24 h post OVA challenge. THROLP is an indicator for plasma leakage, activation of the clotting reaction and the protracted inflammation in the airways, which induced bronchial hyperreactivity. PMID- 1937892 TI - Inhibition of allergen-induced bronchoconstriction in sensitized guinea pigs by orally administered allergen. AB - Crude mite extract (CME) was orally administered to guinea pigs sensitized to CME. It was shown that such treatment reduces the bronchoconstrictive response upon allergen provocation. Isolated tracheae taken from guinea pigs orally administered CME allergen showed less contraction in response to CME as compared to those obtained from sensitized but not orally treated animals. The oral administration of allergens seemed to attenuate the bronchial hyperresponsiveness of sensitized animals to a non-specific chemical stimulus (histamine). IgE antibodies titrated by 8 days passive cutaneous anaphylaxis, and IgG1 and IgG2 antibodies measured by ELISA were comparable in the sera obtained from animals before and after CME treatment. PMID- 1937893 TI - Smooth muscle mechanics: implications for airway hyperresponsiveness. AB - Human bronchial smooth muscle preparations from 10 freshly dissected pneumonectomy samples were evaluated for their mechanical characteristics and compared with results obtained for similar samples obtained from porcine trachea. Length-tension relationships of in vitro smooth muscle were evaluated for passive stretching as well as active isometric force generation and isotonic shortening using electrical field stimulation. At the length (Lmax) producing maximal force (Pmax) resting tension was very high (60.0 +/- 8.8% Pmax) compared with porcine trachealis (5.2 +/- 2.3% Pmax). Maximum shortening was 25.0 +/- 9.0% at a length of 75% Lmax with suboptimal shortening occurring at Lmax (12.0 +/- 3.4%) for the human bronchus, whereas optimal shortening of porcine trachealis (71.4 +/- 3.6%) occurred at Lmax. Morphometric evaluation revealed threefold less muscle per cross-sectional area of tissue for human (8.7 +/- 1.5%) versus porcine (24.8 +/- 1.9%) preparations. We conclude that the high passive tension and the decreased maximum shortening are produced by a relatively large load which must be overcome for the muscle to shorten, presumably provided by the greater connective tissue elastic component present in the airway. We suggest that a decrease in airway wall elastance would increase smooth muscle shortening, thereby leading to excessive responses to contractile agonists as seen in vivo in asthma. PMID- 1937894 TI - Effects of theophylline compared with prednisolone on late phase airway leukocyte infiltration in guinea pigs. AB - The effects of prednisolone, theophylline or salbutamol treatment were studied on leukocyte numbers in bronchoalveolar lavage (BAL) fluid taken 72 h after ovalbumin challenge in sensitized guinea pigs. Ovalbumin challenge resulted in an approximate 3-fold increase in the number of eosinophils in BAL fluid. This increase was significantly reduced by oral administration of prednisolone (59% inhibition with 10 mg/kg x 2) theophylline (56% with 50 mg/kg x 2) but not by salbutamol (10 mg/kg x 2). A comparison with the bronchodilator potency of the above drugs indicated that in guinea pigs salbutamol appears relatively selective as a bronchodilator, prednisolone is selective as an inhibitor of eosinophilia whilst theophylline displays a balance of both activities. PMID- 1937895 TI - Antigen-induced modulation of autonomic and sensory neurons in vitro. AB - We have addressed the hypothesis that the excitability of peripheral neurons is affected during immediate hypersensitivity reactions. Guinea pigs were actively sensitized to ovalbumin. The electrical membrane properties of neurons within the superior cervical ganglion, bronchial parasympathetic ganglion and nodose ganglion were evaluated before, during and after antigen challenge. In all preparations, antigen stimulation induced the release of histamine and arachidonic acid metabolites. Our results support the hypothesis that the excitability of sympathetic, parasympathetic and sensory C-type neurons may be increased during immediate hypersensitivity reactions. PMID- 1937896 TI - Epidemiology of the relationship between exposure to indoor allergens and asthma. AB - A very high prevalence of immediate hypersensitivity to common indoor allergens can be demonstrated among children and young adults, with asthma. Recent progress in the immunochemistry of cat, dust mite and cockroach allergens has made it possible to measure exposure to these allergens and to start to define threshold levels of exposure which increase the risk of sensitization and symptomatic asthma. Indeed, it is already clear that exposure to greater than 2 micrograms group I dust mite allergen (or 100 mites) per gram of dust increases the risk of children developing sensitization and asthma. Furthermore, from studies on patients presenting to emergency rooms with asthma, it is clear that the risk of sensitization to allergens derived from cats or cockroaches or grass pollen is restricted to patients who are exposed to high levels of these allergens. Given the increasing morbidity and mortality of asthma it is clear that therapeutic efforts should be focused on identifying relevant allergens and advising patients about techniques for reducing exposure. PMID- 1937897 TI - Allergen profiles of dog hair and dander, body fluids and tissues as defined by immunoblotting. AB - The sera from 25 patients with clinical type I allergy against dogs were investigated by means of immunoblotting, using extracts of dog hair/dander, skin, hair, saliva, salivary gland, serum and liver. 96% of the patients' sera showed IgE antibodies reactive with 19- and 23-kilodalton (kDa) proteins in the hair/dander extract. The 23-kDa IgE-binding protein was preferentially detected in the hair extract and saliva but not in skin, salivary gland, serum and liver extracts. The 19-kDa band was strongly expressed in skin, but not in hair, serum and liver. Inhibition experiments using the 23-kDa containing extract prepared from hair and the 19-kDa containing extract prepared from skin revealed that these two proteins are likely to be immunologically independent allergens. PMID- 1937898 TI - Synthesis of biologically active recombinant Der f II. AB - A cDNA library corresponding to mite protein was screened employing anti-Der f II antibody. Two possible clones containing plasmids pFL1 and pFL11 were obtained. The two plasmids had insertions of about 500 basepairs. The DNA sequences of the two insertions were determined, from which the amino acid sequences were deduced. The amino acid sequence of the purified native Der f II protein could be determined to 45 residues from the N terminus. As a result of comparison, we concluded that the cDNAs prepared from live Dermatophagoides farinae mite corresponded to the mite allergen Der f II. The recombinant Der f II was biologically active. PMID- 1937899 TI - Basidiomycete allergy: identification and characterization of an important allergen from Calvatia cyathiformis. AB - Basidiomycetes were not considered as major aeroallergen sources until spore traps revealed the prevalence of basidiospores, which were in some cases associated with epidemic outbreaks of asthma. More recently, we established that approximately one third of subjects with respiratory allergic disease were skin prick test positive to basidiospore extracts. Bronchial challenge with these extracts induced reversible immediate and late phase bronchospasm in sensitive subjects. Screening individual RAST-positive sera for reactivity to immunoprinted Calvatia cyathiformis spore extract indicated that a basic component with pI 9.3 reacted with 63% of test sera. Further analysis by RAST and immunoprint (IP) inhibition showed that this component, Cal c Bd9.3, appeared to cross-react with spore extracts from 3 of 5 other species tested. To isolate this component for additional analysis, a protocol was used with two sequential stages of preparative isoelectric focusing (IEF) followed by hydrophobic interaction chromatography. This yielded purified Cal c Bd9.3 that retained IgE-binding activity by IP, was a single band by IEF and SDS-PAGE (16 kD) analysis when stained with Coomassie blue. Double diffusion in gel with rabbit antiserum to Cal c BD9.3 demonstrated a single precipitin band in crude extract that was identical to that obtained with purified Cal c Bd9.3. By IP this antiserum recognized pure Cal c Bd9.3 and the 9.3 band in crude extracts from C. cyathiformis and 3 other species, corroborating the cross-reactivity. However, other bands were also recognized. These studies indicate that basidiospores are major fungal aeroallergens, many of which contain a common basic allergen to which most sensitized subjects react. PMID- 1937900 TI - Analysis of 'clean' air samples by scanning and transmission electron microscopy and X-ray probe micro-analysis. AB - Air samples taken from the clean air over Bristol were examined using scanning, transmission and X-ray probe micro-analysis. A diversity of material was identified demonstrating the importance of man-made pollutants which have the potential to produce lung damage in addition to pollen moulds. PMID- 1937901 TI - Ultrastructural localization of the allergen Der p I in the gut of the house dust mite Dermatophagoides pteronyssinus. AB - The sites and concentrations of Der p I within the house dust mite were determined. Highest concentrations were found in the epithelium of the posterior end of the mite stomach, implying that this is the site of Der p I synthesis and secretion. PMID- 1937902 TI - A low molecular weight allergen of white birch (Betula verrucosa) is highly homologous to human profilin. AB - Cloning of allergens has contributed substantially to the understanding of mechanisms in allergic diseases by providing information about the sequence and hence biological functions of allergens. The major birch pollen allergen, Bet v I [Breiteneder H, et al: EMBO J 1989;8:1935-1938] and the white-faced hornet venom allergen (antigen 5) [Si Yun Fang K, et al: Proc. Natl. Acad. Sc. USA 1988;85:895 899] were shown to be highly homologous to pathogenesis-related proteins of plants. In the case of the major allergen of house dust mite, Der p I, homology to proteases was demonstrated. Therefore, the proposed biological function of these IgE-binding proteins might be related to their allergenic potential. In this paper we tentatively identify a ubiquitous family of low molecular weight allergens as profilins. The identification is based on a sequence homology, (b) binding to poly(L-proline), and (c) immunological cross-reactivity. Recombinant birch profilin was purified to homogeneity and showed the same properties as natural profilins. PMID- 1937903 TI - Tribolium confusum (confused flour beetle, rice flour beetle)--an occupational allergen in bakers: demonstration of IgE antibodies. AB - Specific IgE to proteins from Tribolium confusum (TC), a flour beetle, was detected in 9/125 sera of subjects exposed to rye and wheat flour. TC RAST was not inhibited by Dermatophagoides pteronyssinus, rye or wheat flour. Immunoblot experiments showed specific binding to three proteins from adult TC or pupae, not present in rye or wheat flour. These findings suggest that TC might act as an occupational allergen in a proportion of bakers. PMID- 1937904 TI - Investigation of house dust mite (Dermatophagoides pteronyssinus) allergen extracts prepared from purified mite bodies and whole mite culture. AB - Allergen extracts prepared from purified mite bodies (PMB) and whole mite culture (WMC) were investigated by using in vivo and in vitro methods. PMB showed a more complex allergen pattern than WMC. In PMB, 6 out of 16 allergens could be detected as major allergens. In WMC, 5 out of 10 allergens could be detected as major allergens. Both extracts contained the same amount of the major allergen Der p I. By skin prick testing comparable results were obtained with both extracts. Investigation of the reproducibility showed that 15 production lots of PMB could be produced in a high conformity according to their allergenic potency and their protein and allergen composition. PMID- 1937905 TI - Determination of specific IgE antibodies to benzylpenicillin and amoxicillin in sera from patients allergic to beta-lactams. PMID- 1937906 TI - Intracellular mechanisms regulating exocytotic secretion in mast cells. AB - The release of inflammatory mediators from mast cells occurs by a regulated exocytotic process. We have been able to study the intracellular events in this pathway by permeabilizing the plasma membrane of rat peritoneal mast cells and stimulating exocytosis by providing both Ca2+ and a guanine nucleotide. By this approach we have obtained evidence for the participation of at least two guanine nucleotide binding proteins in the control of exocytosis. We have also shown that ATP is unnecessary for the final events, but that it does have a number of modulatory functions, for instance in the control of the effective affinity of the proteins that bind Ca2+ and GTP. There is also evidence for a protein dephosphorylation in the later stages of the control pathway. PMID- 1937907 TI - Basic mechanisms of cellular priming and release of inflammatory mediators. AB - Simultaneous stimulation of human neutrophils (PMN) with the receptor-mediated activator formyl-met-leu-phe (FMLP) and the G protein activator sodium fluoride (NaF) resulted in the synergistic generation of leukotrienes. Activation of human platelets with thrombin and NaF showed an additive formation of 12-HETE. This enhancement in lipid mediator generation correlated with a time-dependent synergism in G protein activation after sequential stimulation of intact cells with FMLP and NaF or thrombin and NaF, respectively. In addition, polymerization of actin, an early event in cell activation, was enhanced after incubation with cytokines and FMLP. PMID- 1937908 TI - Regulation of IgE responses to inhaled antigens: cellular mechanisms underlying allergic sensitization versus tolerance induction. AB - Previous research from our laboratory has established that the natural response of the respiratory mucosal immune system to inhaled allergens involves initial 'recognition' accompanied by transient low-level IgE production, followed by the development of protective immunological tolerance. Recent studies indicate that the crucial cellular events in this process occur at the level of the upper respiratory mucosa and in the local draining lymph nodes. Salient findings from ongoing studies, detailed below, include identification of a highly developed network of dendritic antigen-presenting cells within the airway epithelium which trap inhaled antigen, and definition of the surface phenotype of the suppressor T cells mediating tolerance as TcR gamma + delta +. PMID- 1937910 TI - The Carl Prausnitz Lecture. Biographical sketch of Dr. Alec H. Sehon. PMID- 1937909 TI - New concepts of IgE regulation. AB - B cell switch to IgE expression is mediated by IL-4 and is regarded as a T helper cell-related phenomenon. In this overview we describe that IgE switch can also be induced by mast cell/basophil like cells (from splenic non-B, non-T cells), activated by IgE receptor cross-linking and/or IL-3 which results in IL-4 production by these cells. Furthermore, activated mast cells produce their own growth factors, IL-3 and GM-CSF. Thus, activation of mast cells can provoke an ongoing local allergic reaction as long as antigen confrontation is maintained, a process which is sustained by further IgE production as well as renewal of mast cells. It is furthermore demonstrated that in certain established immune situations the IgE response may become independent of IL-4, namely in the spontaneous in vitro IgE expression of cells from atopic individuals as well as in an in vitro antigen-induced secondary IgE response of spleen cells derived from previously immunized mice. Thus, IgE-switched B cells may persist in vivo and may represent a pool of potentially IgE-producing cells. Finally, a selective inhibition of the IgE response is described in vitro and in vivo by the use of so called non-anaphylactic monoclonal anti-IgE antibodies. Such antibodies bind to surface IgE+ B cells, but not to IgE-sensitized mast cells, and thereby inhibit IgE responses. Non-anaphylactic antibodies blocked the binding of allergen specific IgE to mast cells by competing with the Fc epsilon on these cells. As a consequence they do not induce but rather prevent allergen-induced mediator release by mast cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937911 TI - Isolation and characterization of a 60-kDa IgE-binding component derived from sera of atopic patients (atopic dermatitis). AB - The low-affinity receptor for IgE (Fc epsilon RII, CD23) and the related soluble IgE-binding factors (IgE-BF; sCD23) play an important role in IgE regulation. Sera of patients suffering from atopic dermatitis (AD) were reported to contain an IgE-binding component with a molecular weight of 60 kD. The aim of our studies was the isolation and characterization of the 60 kD component. Sera of patients with AD were fractionated by ammonium sulfate precipitation (10-90%). The fractions were analyzed with regard to their IgE and their IgE-BF contents. Furthermore, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and subsequent autoradiography with 125I-labeled human IgE (PS) was performed to detect IgE-binding activity. The major amount of IgE as well as IgE-BF was obtained within the 30-50% ammonium sulfate precipitation. In addition, IgE binding activity was precipitated at 60% saturation. Separation by gel filtration under physiological conditions indicated IgE-BF with molecular weight of greater than 100, 60, 25 and 15 kD. Rechromatography of the greater than 100-kD fraction led to IgE-binding activity with a molecular weight of 60 kD which is not present within normal sera. The data demonstrate that the 60-kD component is partially bound to serum IgE. One may suggest that the complex is involved in the induction and persistence of allergic disorders. PMID- 1937912 TI - Role of CD8 T cells in rat IgE responses. AB - The role of the cytokines interleukin-4 and interferon-gamma in the regulation of IgE responses in the mouse and man have focused on the role of CD4 T cells. In the rat, antigen-specific CD8 T cells, generated following inhalation of antigen, have been shown to be capable of suppressing IgE responses. Repeated intraperitoneal injections of 1 ng ricin and 1 microgram antigen established a long-lived IgE response in both low- and high-IgE responder rat strains (Wistar and Brown Norway). The duration of the IgE antibody response was 204 and 248 days, respectively. Total IgE levels rose from 30 +/- 20 to 39,000 +/- 7,500 ng/ml in the Wistar rat and from 120 +/- 100 to 47,000 +/- 8,000 ng/ml in the Brown Norway rat. An even greater (10(4)-fold) increase was seen in antigen specific IgE antibody levels. Ricin alone had no effect and concomitant or prior stimulation with antigen was required. The proportion of CD4+ and CD8+ cells present in the spleen at the peak of the IgE response was markedly increased compared with animals given ricin or antigen alone. Furthermore, CD8 T cells were approximately 100 times more sensitive to ricin than CD4 T cells. These data suggest that enhancement of IgE responses in ricin-treated animals results from the selective deletion of T cells which suppress IgE and are of the CD8 phenotype. PMID- 1937913 TI - The immune response to anti-idiotype antibodies bearing an internal image epitope of tetanus toxin/toxoid. I. Induction of the humoral immune response. AB - Primary immune responses to tetanus toxoid (TT) and primary and secondary immune responses to a rabbit TT internal image bearing anti-idiotype antibody (Ab2 beta 1) inoculated in Freund's complete adjuvant (FCA), saline (SAL) or syntex adjuvant formulation vehicle (SAF) via the intraperitoneal or subcutaneous route, were examined in mice. High anti-TT antibody (Ab3) titres are reported although the titre and persistence of the antibody response varied according to the adjuvant used in the priming and challenge inocula of Ab2 beta 1. Mouse Ab3 antibodies were elicited in mice inoculated with rabbit Ab2 beta 1 antibodies which in turn were elicited by an inoculum of mouse monoclonal anti-TT Ab1 antibody. Ab3 was shown to be identical to Ab1 by immunoblot analysis. Primary and secondary immune responses elicited by rabbit Ab2 beta 1 antibody protected mice against a lethal dose of tetanus toxin. PMID- 1937914 TI - Influence of mepacrine on the reaction of adoptive cutaneous anaphylaxis. AB - In a test of adoptive cutaneous anaphylaxis, the influence of the phospholipase A2 inhibitor mepacrine, on the intensity of the local anaphylactic reaction was investigated in the skin of recipients following intracutaneous injection of syngenic immune splenocytes. Injection of the mepacrine solution with preincubated sensibilized splenocytes inhibits the cutaneous anaphylactic reaction after a single intravenous administration of allergen to recipients. The inoculation of immune splenocytes, preincubated in mepacrine but without the phospholipase A2 inhibitor, to the skin of syngeneic recipients is accompanied by less suppression of the local skin anaphylactic reaction than with a common injection of mepacrine with immune splenocytes. PMID- 1937915 TI - Experimental allergic encephalomyelitis-prophylactic and therapeutic treatment with the cyclooxygenase inhibitor piroxicam (Feldene). AB - Prophylactic administration of Piroxicam (Feldene), a reversible inhibitor of prostaglandin biosynthesis, significantly reduced the occurrence of paralytic signs and the amount of antibodies against myelin basic protein in the model of mild acute experimental allergic encephalomyelitis in the Lewis rat. Mononuclear infiltration of the central nervous system remained unaffected. A therapeutic intervention with piroxicam, however, increased paresis and CNS pathology. Immunohistochemical studies revealed an increased proportion of ED1-positive macrophages and monocytes in the infiltrates of the spinal cord in animals treated with piroxicam. Possible reasons for the different effects of the prophylactic and therapeutic treatment are discussed in the study. PMID- 1937916 TI - Selective impairment of T lymphocyte activation following contact sensitization with oxazolone. AB - We have previously reported that topical exposure of mice to oxazolone results in the appearance of regulatory mechanisms which markedly depress lymph node cell (LNC) proliferative responses to subsequent challenge with the same chemical. In the present study, we have sought to identify the cellular targets for such immunoregulation. Autoradiographic analyses revealed that although pre-exposure to oxazolone caused a substantial reduction of paracortical hyperplasia following challenge, the frequency of proliferating cells in lymphoid follicles was slightly increased. That B lymphocyte responses are unaffected by oxazolone induced immunoregulation was confirmed by investigation of anti-hapten antibody formation by draining LNC. Challenge with oxazolone resulted in an accelerated antibody response in mice previously exposed to the same chemical. These data reveal that the active immunoregulation induced following sensitization with oxazolone is selective for T lymphocytes. Evidence is presented that CD4+ and CD8+ T lymphocytes possess equivalent sensitivity to these mechanisms. PMID- 1937917 TI - Histamine stimulation of the nasal mucosa does not induce prostaglandin or leukotriene generation or induce methacholine hyperresponsiveness. AB - To further define the role of histamine in the nasal mucosa, we studied the possible effect of histamine provocation on the generation of prostanoids and leukotrienes, and on the induction of hyperresponsiveness to methacholine. In separate experiments, we performed nasal challenges with histamine and measured by gas chromatography negative ion mass spectrometry and by radioimmunoassay after high-performance liquid chromatography the levels of prostanoids and leukotrienes, respectively, in recovered nasal lavages 10 min after challenge. Hyperresponsiveness to methacholine was tested in both nostrils 24 h after unilateral provocation with histamine. Our data suggest that histamine induced an immediate symptomatic response, but neither led to the generation of prostaglandins or leukotrienes nor induced hyperresponsiveness to methacholine. These results differ from those achieved after antigen stimulation and emphasize the importance of mediators in addition to histamine in the allergic reaction. PMID- 1937918 TI - Characterization of eosinophils in a continuous ambulatory peritoneal dialysis patient with eosinophilic peritonitis. AB - A continuous ambulatory peritoneal dialysis patient developed eosinophilic peritonitis and was followed for 7 months. After 1 month, the peritonitis resolved, with a concomitant drop in percentage of hypodense eosinophils (Eos) recovered from peritoneal dialysate (PD) as well as a drop in fluid major basic protein levels. Blood eosinophil differential percentages were low, but the percentage of hypodense Eos in the blood tended to be relatively increased. Stool samples showed no evidence of parasitic infection, and epicutaneous skin tests were negative. Leukotriene C4 levels remained relatively constant as did white blood cell counts. Flow cytometric analysis of lymphocytes and granulocytes from PD and blood revealed high levels of CD23-positive lymphocytes. PMID- 1937919 TI - Cypress (Cupressus sempervirens) pollen allergens: identification by protein blotting and improved detection of specific IgE antibodies. AB - On the basis of results of an investigation of the effects of different treatments employed, a dialysed and reduced extract of Cupressus sempervirens was separated electrophoretically on sodium dodecylsulphate-polyacrylamide gels before being transferred and then fixed with glutaraldehyde to nitrocellulose membrane. Probing with sera from 91 subjects allergic to C. sempervirens pollen followed by detection of bound IgE antibodies with [125I]-labelled anti-human IgE revealed 17 IgE-binding proteins in the molecular weight range 14-96 kilodaltons (kDa). One component, of molecular weight approximately 42 kDa, reacted with IgE antibodies in the sera of 81.3% of the allergic subjects and, for each of the subjects, this component bound the greatest quantity of IgE. Almost 50% of the sera recognized only the approximately 42 kDa component, reinforcing the conclusion that this component is the major allergen of C. sempervirens pollen. A comparative study employing C. sempervirens pollen allergen discs prepared commercially or in the laboratory showed that values of the uptakes of [125I] anti-IgE indicating the presence of pollen-reactive IgE antibodies obtained with the latter discs were consistently higher (means 4.5 vs. 0.88), and that false negative results were obtained when many sera were used with the commercial discs. The results of this study provide an essential basis for the production of standardized, safe and effective C. sempervirens pollen extract applicable to diagnosis and therapy of cypress pollen allergy. PMID- 1937920 TI - Immunoregulation of endometrial and jejunal epithelia sensitized by infection. AB - The hypothesis was tested that the uterus of the rat orally infected with the parasite Trichinella spiralis becomes hypersensitized and that subsequent antigenic challenge affects functions in the endometrial epithelium. Results of experiments comparing the immunological responsiveness of isolated rat uterus with that of the jejunum supports our hypothesis. Antigenic challenge of uterus mounted in Ussing-type chambers causes an elevation in transuterine short circuit current (Isc) of 6.4 +/- 0.8 microA/cm2. The transduction of the antigenic signal to elicit the electrophysiological response involves 5-hydroxytryptamine (5-HT) working through a nerve-independent pathway. The antigen-stimulated rise in Isc peaks approximately 3 min after challenge. The uterine response is blocked by diisothiocyanostilbene-2,2'-disulfonic acid, an inhibitor of bicarbonate-chloride exchange. The antigen-evoked change in jejunal Isc is biphasic, peaking at 1.5 and approximately 4.0 min after challenge, and is about 10-fold greater in magnitude than the Isc in the uterus. The transductive pathway in the jejunum involves 5-HT, histamine and prostaglandin acting partly through intrinsic nerves. The jejunal response to antigen is inhibited by diphenylamine-2 carboxylate, a chloride channel blocker. Changes in net ion transport which are primed by infection and evoked by antigen are apparently triggered by local anaphylaxis in both the uterus and jejunum. PMID- 1937921 TI - Appearance of macrophage migration inhibition factor in patients with systemic reactions to bee venom. AB - Cellular responses in bee venom (BV) allergy is a controversial issue. Previous studies could not reach an agreement whether this mechanism is activated as a result of allergic sensitization to bee venom. All previous works have used lymphocyte proliferation as their method to analyze cell-mediated immunity. In the present work, we tried to explore whether the production of macrophage migration inhibition factor (MIF), which is another in vitro correlate with cellular responses, is increased in these patients. We also examined which of the major antigenic components of BV played a significant role in the cellular response. Peripheral blood lymphocytes from 10 patients with systemic allergic reactions to bee sting and 9 healthy volunteers were examined for their ability to induce positive MIF responses. Macrophage inhibition was significantly increased in allergic patients when tested with BV, phospholipase A2 (PLA2) and with melittin. Positive MIF responses to other components were also more common in allergic patients than in the control group. Our results indicate that cellular response to BV is expressed in patients with systemic allergic reaction to BV. When major antigenic components of BV are examined, PLA2 seems to play the major role in inducing this response. PMID- 1937922 TI - Antigen dose-dependent regulation of B epsilon-memory cell expression. AB - The data presented in this study document that the phospholipase A2 (PLA2) specific IgE antibody response in high responder CBA/J mice is solely dependent on the antigen dose used for immunization. Repeated injections of minute doses (MD) of antigen (0.1 microgram/mouse) induce a persisting high level of PLA2 specific IgE antibody titer, whereas large doses (LD) (10 micrograms/mouse) induce a persisting low level of IgE. The IgG antibody titers are the same under both conditions. The low level IgE immune status induced by repeated LD is irreversible and cannot be boosted by MD. In contrast a single LD primes for a secondary IgE response which can be recalled by MD. A high level of PLA2-specific IgE antibodies induced by MD can be downregulated by a single intervening LD of antigen. A low level IgE immune status can be transferred with spleen cells of mice immunized with LD into naive syngeneic recipients, which then fail to mount a high level IgE response upon injection of MD of antigen. The experiments reveal two countercurrent processes, induction of B epsilon-memory cells after a single LD and additional activation of a persisting IgE-specific cellular suppression mechanism after repeated LD of antigen. These properties make the system suitable for the analysis of cellular interactions and of potential desensitization protocols. PMID- 1937923 TI - Anaphylaxis is enhanced by increased absorption of antigen in postinflammatory state. AB - Hemagglutinating antibodies and cell-mediated immunity are increased when antigens are injected intraperitoneally (i.p.) into rats during the healing phase of a chemical peritonitis. In the present work, the anaphylactogenic effects of either sensitization or challenge were increased when any of three different antigens were injected i.p. in the postinflammatory state. The postinflammatory state made it possible to sensitize rats for anaphylaxis without any adjuvants at all. Lymph nodes draining the peritoneal cavity had evidence of enhanced absorption of inoculum in the postinflammatory state. PMID- 1937924 TI - Allergic hepatitis in guinea pigs induced by 2,4,6-trinitrophenyl liver protein conjugate. AB - Experimental drug-induced allergic hepatitis was induced in guinea pigs which had been immunized to the 2,4,6-trinitrophenyl (TNP)-conjugated liver protein first peak (TNP-LP1) emulsified in complete Freund's adjuvant (CFA). Delayed-type hypersensitivity (DTH) was elicited in the immunized animals by intradermal challenge with TNP-LP1. When TNP-LP1 was introduced into the liver via the mesenteric vein, allergic hepatitis was provoked. Histological examination of the liver revealed massive monocytic infiltration and focal hepatic necrosis in the periportal areas. Blood biochemical analysis showed increased levels of glutamate oxalacetate transaminase (GOT) and total bilirubin. TNP-modified hepatocytes were found to be effective as a challenge elicitor to the immunized animals to induce both DTH skin reaction and allergic hepatitis. In the latter case, the severity of the lesion was stronger than that observed by the challenge with TNP-LP1. PMID- 1937925 TI - Survey of Hanganutziu and Deicher antibodies in operated patients. AB - The appearance of Hanganutziu and Deicher (HD) antibody in the sera of patients suffering from various diseases, including malignancies of some organs and liver disorders, was investigated by enzyme-linked immunosorbent assay using N glycolylneuraminyl-lactosylceramide (HD3) and 4-O-acetyl-HD3 as the antigenic molecules. More than 25% of sera from patients suffering from malignancies, cholelithiasis and liver cirrhosis had HD antibody, whereas none of 41 sera from healthy persons had HD antibody. The percentage of HD antibody-positive patients was similar in stages I, II and III of gastric cancer and recurrence cases. Antibody titers of the positive patients in each stage were also not different from those in each other stage. These results indicated that HD antigenic expression on cancerous tissue is not dependent on the cancerous malignancy. The HD antibody level was elevated after surgical removal of cancerous tissues in 5 of 6 patients examined, indicating that tumor growth absorbed the serum antibody. Serum antibody against 4-O-acetyl-HD3 was detected independently of HD3 antibody in some cases; however, in most cases, correlation between the two antibody titers was observed. PMID- 1937927 TI - Interleukin-4-induced IgG subclass and IgE secretion by mononuclear cells from atopic donors. AB - To investigate the effect of interleukin-4 (IL-4) on the secretion of IgG subclasses and IgE in atopic individuals, peripheral blood mononuclear cells from 10 atopic and 10 normal donors were incubated with IL-4, and the production of IgE, IgG1, IgG2, IgG3, and IgG4 was determined after a 14-day culture period. Like normal peripheral blood mononuclear cells, atopic mononuclear cells were stimulated by IL-4 to secrete IgE and IgG4, but not the other IgG subclasses. This response was in the same quantitative ranges in both donor groups. Addition of interferon gamma to IL-4-containing cultures efficiently antagonized the IL-4 induced IgE and IgG4 secretion. These results do not support the hypothesis that an atopic condition is due to a discordant effect of IL-4 on IgE compared to IgG4 production or to an altered response to the potent antagonist interferon gamma. PMID- 1937926 TI - Bradykinin induces eosinophil accumulation in the rat pleural cavity. AB - Intrathoracic injections of bradykinin (1-100 micrograms/cavity) induced a dose dependent increase in the number of eosinophils recovered from the rat pleural cavity 24 h later. Eosinophilia by bradykinin was preceded by a marked pleural neutrophil influx within 6 h and was absent only 72 h following stimulation. Bradykinin (10(-9)-10(-5) M) failed to induce in vitro eosinophil chemotaxis, indicating that its in vivo effect must be mediated by an intermediate messenger. BW 755C (25 mg/kg) and the more selective lipoxygenase inhibitor BW A4C (20 micrograms/cavity) suppressed the pleural eosinophilia induced by bradykinin (50 micrograms/cavity), whereas the platelet-activating factor (PAF)-acether antagonist BN 52021 was inactive. We conclude that bradykinin is able to attract eosinophil in vivo by a mechanism independent of PAF-acether and sensitive to the blockage of the lipoxygenase pathway. PMID- 1937928 TI - Comparative antigen analysis of different life stages of Schistosoma mansoni by crossed immunoelectrophoresis. AB - Two-dimensional (crossed) immunoelectrophoresis was used for analysis of soluble antigen extracts obtained from the three developmental stages, cercariae, adult worms and eggs, of Schistosoma mansoni by using homologous hyperimmune sera produced in sheep. The antigenic relationships between the three stages as well as the possible relationship to the intermediate snail host were studied. Seven antigen components were shown to be shared between all three life stages of S. mansoni. Furthermore, one antigen was common to adult worm and snail, and one other antigen was shared between cercaria and snail. By using an intermediate gel containing lectin in the antigen-antibody system or by enzyme staining of the immune precipitates it was possible to identify schistosome antigens possessing lectin reactivity or enzyme activity. Characterization of enzyme activities revealed three individual precipitating antigens in adult worm of S. mansoni possessing esterase, leucyl-glycyl-glycine peptidase and phenylalanyl-leucine peptidase activities, respectively. One further precipitinogen with malate dehydrogenase activity was identified for all three life stages. PMID- 1937929 TI - Time course of cellular infiltration in the nasal mucosa during the immediate allergic reaction. AB - In 23 patients with allergic rhinitis, biopsies of the nasal mucous membrane were taken at one of the following times after challenge of one nostril with allergen: 0 (baseline) (n = 7), 1/2 h (n = 6), 1 h (n = 5), and 2 h (n = 5). In the nostril stimulated by allergen there was a transient early phase influx of eosinophils while the numbers of stainable mast cells decreased, probably due to their degranulation. In the contralateral unstimulated nostril, there was no change in numbers of eosinophils but the numbers of stainable mast cells decreased. These results support the proposed role in allergic rhinitis of the mast cell and eosinophil, and suggest that the eosinophil may be a rapidly mobilized effector cell. PMID- 1937930 TI - Effect of histamine on tumor necrosis factor production by human monocytes. AB - This study was aimed at evaluating the effect of histamine on tumor necrosis factor (TNF alpha) secretion by purified human blood monocytes. TNF alpha was measured by radioimmunoassay. Histamine caused a dose-dependent inhibition of lipopolysaccharide-induced TNF alpha production from human blood monocytes, averaging maximally 50% at 10(-5) M. Preincubation of mononuclear cells with an H2 antagonist (cimetidine), but not with an H1 antagonist (promethazine) prevented this inhibitory effect of histamine. In conclusion, histamine causes, in vitro, a depression of TNF alpha secretion by human monocytes through activation of H2 receptors. PMID- 1937932 TI - Serum antibody responses in mice to intermittent inhalation of ovalbumin dust. AB - Serum antibody production and induction of antibody tolerance were monitored in mice following intermittent inhalation of ovalbumin dust (mass concentration = 4.2 mg m-3; diameter of 80% of particles less than 2.6 microns). Repeated inhalation of microgram quantities of dust stimulated serum antibody production and development of tolerance. The sequence of these responses is analogous to that following oral presentation of antigen, but is produced by a much lower dose when antigen is presented via the respiratory tract. PMID- 1937931 TI - Interleukin-4 gene expression in human peripheral blood mononuclear cells. AB - Interleukin-4 (IL-4) mRNA was detected in normal human peripheral blood mononuclear cells (PBMC) stimulated with concanavalin A by Northern blot analysis. The signal was undetectable in PBMC before the stimulation, but became detectable 3 hrs after the stimulation and reached a maximum in 3-6 h and disappeared gradually thereafter. Immunosuppressive drugs such as ciclosporin, hydrocortisone and prednisolone inhibited the IL-4 mRNA expression dose dependently. Interferon-gamma did not show any inhibitory effect on IL-4 gene expression. PMID- 1937933 TI - Releasability of airway macrophages in bronchial asthma. PMID- 1937934 TI - Biologically active heparin coating in medical devices. PMID- 1937935 TI - Ultrafiltration and pressure profiles in continuous arterio-venous hemofiltration studied by computerized scintigraphic imaging. AB - Clotting of the filters in continuous arterio-venous hemofiltration (CAVH) has been frequently related to filtration pressure equilibrium (FPE). The geometry of the filter and the blood flow, together with filtration fraction, are the factors affecting FPE. A new method based on scintigraphic imaging of the filter is described to demonstrate FPE and identify the operational conditions influencing it. A radiolabelled marker molecule (albumin macroaggregates + Tc99) is added to the blood circulating at various flows through the filter. Changes in the concentration of this molecule detected by a gamma camera are used to calculate the water fluxes in different sections of the filter. When the curve reaches a plateau, no further changes occur and FPE is achieved. The study used Amicon D-30 hemofilters and FPE points were achieved for blood flows of 75, 110 and 150 ml/min respectively 8 cm, 12 cm and 18 cm from the inlet. The study not only demonstrates the occurrence of FPE, but also identifies the length of the filter required at a given blood flow to avoid FPE (achieving less clotting and lower heparin requirement). The Amicon diafilter family, having filters of different length, is useful for "personalizing" the filter in CAVH. PMID- 1937936 TI - Peritoneal dialysis using bicarbonate-containing solution sterilized by ultrafiltration. AB - We performed acute peritoneal dialysis on eight end-stage renal disease patients using a bicarbonate-containing solution sterilized by ultrafiltration through polyamide filters. The patients tolerated the procedure well; their azotemia and metabolic acidosis improved. PMID- 1937937 TI - Temporary mechanical circulatory support for severe cardiac failure: experimental study. AB - We describe a technique for mechanical cardiac assistance in an acute model of severe cardiac failure. Cardiac dysfunction was induced by a high dose of halothane in 13 dogs. Seven served as controls. Following median sternotomy, a pneumatically driven device was implanted in the other six dogs in a para-aortic position, using a simple surgical technique without cardiopulmonary bypass. The aorta was cross-clamped during cardiac assistance. During hemodynamic studies, the seven control animals with induced cardiac failure showed high end-diastolic left ventricular and right atrial pressures with low cardiac index and systolic left ventricular and aortic pressures. All dogs in this group died within 30 minutes. Use of a monovalvular cardiac assist device in the experimental group of six dogs to pump blood from the aortic root to the descending aorta in a counterpulsation manner, confirmed good preservation of systemic hemodynamic parameters after induction of heart failure. All animals in this treated group survived more than 45 minutes. Hemodynamically, the device acts as a new ventricle and the impaired left ventricle functionally becomes a left atrium. This condition is clinically appropriate for recovery of left ventricular function in severe acute myocardial failure. PMID- 1937938 TI - Implantable glucose sensors: comparison between in vitro and in vivo kinetics. AB - This study was aimed at validating the in vitro estimated response characteristics of implanted glucose oxidase/H2O2 electrodes with respect to their in vivo function. Monoexponential non-linear regression analysis of sensor current vs. time curves in response to square alterations in glucose concentration gave response times T95 of between 1 and 5 min. Non-primed glucose infusions were applied to dogs with these electrodes implanted subcutaneously. The simultaneously monitored in vivo data were subjected to non-linear regression analysis. The time constants T of increases or decreases after starting or ending the glucose load were (mean +/- SEM) 53 +/- 10 and 26 +/- 4 min (significant difference, p less than 0.05) in sensor current, 28 +/- 8 and 15 +/- 2 min (NS) in whole blood, and 26 +/- 5 and 18 +/- 2 min (NS) in plasma. The in vivo kinetic patterns of sensors were not related to their in vitro response times. Non-linear regression analysis of in vitro responses of glucose sensors under clearly defined conditions is recommended as a basis for further studies. The physiological delay in the subcutaneous glucose system needs more attention in this field of research. PMID- 1937939 TI - Heparinized polyurethane surface through ionic bonding of heparin. AB - Surface heparinization through an ionic bond is one of the methods used to improve polyurethane blood compatibility. Chains of poly(amido-amine), a tertiary aminic polymer capable of forming stable complexes with heparin, were either surface-grafted on polyurethane or interconnected with polyurethane chains using hexamethylenediisocyanate as cross-linking agent. In the latter case, a new material (PUPA) is formed with a heparin adsorbing capacity higher than poly (amido-amine) surface-grafted polyurethane. By changing the percentages of the components, different series of PUPA materials can be obtained with different physico-chemical properties. The ATR/FT-IR technique was used to characterize the new materials in the native and in the heparinized state. PUPA solution was used to coat commercial biomedical devices and they were also characterized physicochemically using ATR/FT-IR. PMID- 1937940 TI - Ex vivo removal of IgE in atopic asthma by extracorporeal plasmoimmunoadsorption (EPIA): development of a clinical adsorbent. AB - We have developed an immunoadsorbent (IA) for ex vivo removal of IgE after in vitro screening of matrix (Sepharose and tresyl-activated Toyopearl) and ligand (monospecific rabbit polyclonal anti-IgE antiserum and monoclonal antibodies (Abs) or their Fab fragments). Specific adsorptive capacity (SAC) for IgE was maximal in Sepharose-based IA with both types of Abs. Fab-containing IA on Sepharose retained 70-90% of the SAC of native Ab-containing IA. Toyopearl-based IA showed comparable SAC under static conditions but worked unsatisfactorily under continuous flow conditions. To assess the complement-activating capacity (CAC) of IA in vitro anaphylatoxin (C3a, C4a, C5a) generation was applied. CAC was directly related with the amount of immobilized Ab ligand, without depending on Ab specific activity. Fab-containing IA showed more CAC than native Ab containing IA, and polyclonal IA more than monoclonal IA. Therefore, IA for IgE apheresis were prepared from native monoclonal Abs and CNBr-activated Sepharose CL 4B under aseptic conditions and packed into a glass column. This IA was used in 17 clinical IgE apheresis treatments of five atopic asthma patients. No substantial side effects were observed; in vivo IA effectively removed IgE from plasma (83 to 98%). PMID- 1937941 TI - Inhibition of complement activation with EDTA in vivo during sham hemodialysis. AB - To check whether in vivo EDTA prevents complement activation resulting from blood contact with the dialyzer membrane, sham hemodialysis (HD) was performed in seven healthy volunteers using Cuprophan hollow-fiber dialyzers. Blood samples were drawn from the arterial and venous blood lines of the dialyzer before and after EDTA was infused into the arterial line. Venous line plasma C3a concentrations before EDTA infusion were significantly higher than after EDTA. Also, venous line plasma C3a concentrations before and after EDTA infusion were significantly higher than in the arterial line. These results indicate that complement activation can be attenuated by EDTA during sham HD. Technical improvements in the procedure may permit complete inhibition of complement activation. PMID- 1937942 TI - Cellular mechanisms of artificial peptides binding to HLA. AB - On the basis of the consideration that cell-free models cannot precisely mimic the complexity of the intracellular environment, we used a system to investigate the mechanisms that enable antigen-presenting cells (APC) to bind exogenous peptides through their human leukocyte antigen (HLA) molecules. We evaluated the uptake of the radiolabeled peptide 17-29-Tyr of influenza virus matrix protein by B-EBV cell lines, under various conditions. The results can be summarized as follows: a) the kinetics of peptide binding and release are very fast in living, fully competent cells; b) the peptide-HLA complexes are short-living and the DR molecules continuously undergo peptidic exchange; c) using glutaraldehyde-fixed cells, the kinetics of the two phenomena are slow, closely resembling those observed with the same peptide and purified, immobilized DR molecules. The data suggest that in APC, cellular mechanisms are operative that increase the efficiency of both loading and unloading of Class II HLA with exogenous peptides. This is likely to be related to the recycling of Class II molecules to intracellular compartments, were binding takes place. The observation that the HLA-peptide complex is a dynamic structure, suggests the possibility of replacing natural peptides with synthetic ones at this level, in order to regulate the immune response. PMID- 1937943 TI - Formula predicting survival in patients with invasive cutaneous malignant melanoma. AB - Popescu et al. (Mayo Clin Proc., 65 (1990) 1293-1302) reported survival data in 107 patients who were diagnosed as having malignant melanoma during the years 1950-1985. Survival was evaluated by using the Kaplan-Meier method. A microcomputer program in BASIC for predicting the survival probability after diagnosis in patients with invasive cutaneous malignant melanoma is designed. A formula used in this program is derived from the survival data reported by Popescu et al. A mathematical model of generalized lognormal distribution and a computer program previously published by the author are employed in this study. Analysis of the computer-assisted predicted values and the data reported by Popescu et al. indicates that the program is accurate and reliable with a close agreement in expressing survival probability as a function of time after diagnosis. The computer-assisted predictive formula can determine the relationship between the time and the survival probability, and may be of value for prognostic evaluation of patients. The mathematical model representing the generalized lognormal distribution may be used as a method of parametric analysis of survival data of estimates determined by the nonparametric product-limit method of Kaplan-Meier in certain biological phenomena. PMID- 1937944 TI - A research-oriented medical cost accounting system. AB - Prospective research into factors affecting health care costs for individual patients requires a hybrid information management system with some features usually associated with a medical billing package and other features common to research databases. Furthermore, data collection for such a project must often be done in the field where a portable computer is most convenient. A software program is described which has been developed to address these disparate needs. It allows classification by study protocol assignment and provides multiple summary formats for the assessment of costs. For example, charges can be stratified by specialty, by category of service (pharmacy, room, surgery, respiratory therapy, etc.), by magnitude of expense ('big' vs 'little' ticket items) and so forth. The system design described may prove useful to other investigators studying variation in health care costs. PMID- 1937945 TI - Digital imaging at a community hospital: implications for hospital stays and teleradiology. AB - Two key questions for the cost-effectiveness of digital imaging concern its likely impact on average inpatient stays and the prevalence of applications for teleradiology. Little empirical evidence is available because of the state of the technology, but useful evidence can be drawn from conventional imaging departments. This paper reports a survey of admitting physicians and draws inferences about the likely effects of conversion to digital imaging. Published cost estimates for this Canadian community hospital show that conversion to digital imaging is likely to increase medical imaging costs despite shorter examination times. However, digital imaging could produce net savings hospital wide by improving the efficiency of diagnosis and treatment sufficiently to reduce the length of patient stays. In this sample, no inpatient medical imaging examinations lengthened a stay in a way likely to be averted by digital imaging (95% confidence interval 0% to 2%), and probability testing rejects the hypothesis that digital imaging will reduce hospital stays sufficiently to produce net savings at this hospital. Based on these results, it appears premature to assume that digital imaging will significantly reduce length of stay for most inpatients. On teleradiology, physicians either exchanged films with other medical imaging centres or indicated they would have sent or received teleradiology images for 17% of inpatient medical imaging examinations (95% confidence interval 10-24%). Since outpatient procedures comprise 60% of the medical imaging workload at Victoria General Hospital, further study would be required to estimate overall use of teleradiology. PMID- 1937946 TI - Polychotomous multivariate models for coronary heart disease simulation. II. Comparisons of risk functions. AB - This is the second in a series of papers dealing with models of coronary heart disease. Three different types of statistical models are considered as risk functions: the multivariate logistic model, the Cox proportional hazard model and the Neyman exponential risk avoidance model. The types of models differ in the form hypothesized for the probability of occurrence of coronary heart disease outcomes: incident myocardial infarct, cardiac death, and death from other causes. Although the three risk functions are strikingly different, they can all be tested using the CRISPERS chronic disease simulation system. Simulations were performed using data from North Karelia, Finland. The polychotomous multivariate logistic risk function is convenient for studies involving increasing numbers of risk factors. The Cox proportional hazard regression model is shown to be unsuitable for the cohort dataset used as well as for some of the intended uses of the simulation models. The Neyman exponential risk avoidance model involves time in a quite different fashion. It has the inherent advantage of being easier to relate to underlying biological mechanisms because it is the integral of first order rate equations. It is concluded that more than one risk function should be evaluated for simulations of coronary heart disease. PMID- 1937947 TI - Polychotomous multivariate models for coronary heart disease simulation. III. Model sensitivities and risk factor interventions. AB - This is the third in a series of papers dealing with models of coronary heart disease. Sensitivity analyses of the logistic risk function and the Neyman risk function are reported. The resulting response surfaces are also used to investigate the optimality of the set of values for the risk coefficients. It is shown that the coefficients estimated by maximum likelihood are preferable to the sets from an optimisation procedure. Two different sets of risk coefficients estimated using short periods and entire epochs for the logistic risk function are shown to lead to similar conclusions concerning simulated primary intervention strategies. However, the corresponding risk factor reductions using the Neyman risk function lead to somewhat different effects. Additional information is needed to distinguish between these two assumptions of the risk function used to model coronary heart disease. This underscores the need to understand the effects of the underlying risk function assumed when interpreting simulated outcomes of intervention strategies. PMID- 1937948 TI - Identification of compartmental models for perturbed cell populations using state space parameter estimation techniques. AB - Multiple compartment models for describing synchronous cell kinetics in which cell populations are characterized by DNA content are reviewed. These models are useful for understanding and predicting a cell population's dynamic response to perturbations induced by drugs or radiation. A practical approach is proposed for determining the parameters of these models from empirical cell-cycle data. Specifically, a state-space parameter estimation algorithm based on the maximum likelihood method--developed and coded primarily for engineering applications and commercially available for personal computers and minicomputers--can be applied to DNA specific cell-cycle measurements from synchronized cell populations to produce model parameter estimates. This is demonstrated using published data from a cell-cycle experiment. The results show that the procedure works well, and that with careful experimental planning even better results should be possible. Since the compartmental model is often used to represent biological systems, this approach is widely applicable. PMID- 1937949 TI - Application of ARIMA models to forecast the quality of a French cheese: the 'Comte'. AB - In this paper, we present how we have established ARIMA models giving good predictions for the monthly percentage of Comte without making default for nine cooperatives of Jura (France). We detail how we have chosen the three parameters p, d, q of the ARIMA models for each cooperative and we present a method for selecting p and q based on information criteria. This method has also permitted to compare performances of different information criteria. PMID- 1937950 TI - Application of image analysis to neurological screening through figure-copying tasks. AB - Approaches to the detection and monitoring of neurological dysfunction are generally resource-intensive and often difficult to evaluate objectively. This paper describes an approach to neurological screening which is based on the on line analysis of figure copying tasks, and a variety of features are measured to characterise task execution. It is shown how both qualitative and quantitative measures of individual performance can be obtained in real time. A preliminary experimental study is described to identify appropriate performance indicators for a reference asymptomatic population and for a population with a known abnormal clinical history. The results obtained experimentally demonstrate that the approach proposed, while convenient and efficient in terms of the resources required in implementation, nevertheless offers a high degree of robustness and sensitivity which supports an optimistic view of its clinical viability. PMID- 1937951 TI - Fuzzy realization in clinical test database system. AB - To be able to obtain useful information from medical data easily and quickly in daily use for the hospital staff, it is necessary to construct a proper database system using methodologies suitable for the nature of medical data. From this viewpoint we have developed the clinical test relational database system at Hiroshima University Hospital, which provides the functions of easy on-line retrieval and statistical analysis. Fuzzy query processing based on the fuzzy set theory is adopted in the system. This enables us to use natural linguistic representation and makes it easy to introduce medical knowledge representation. Fuzzy set approaches turn out to be superior in clinical evaluation of laboratory data to the ordinary clear-cut definition of normalcy. PMID- 1937952 TI - Ethnic differences in the anatomical location of colorectal adenomatous polyps. AB - The ratio of right- to left-sided colonic cancer is increasing, but data on the distribution of its usual precursor lesion, the colorectal adenoma, are contradictory. Therefore, we investigated the prevalence of right- and left-sided colorectal adenomatous polyps from January 1, 1970, to September 30, 1989, using the study design of "epidemiologic necropsy" and the autopsy files of The Johns Hopkins Hospital. Compared with the decade of the 1970's, the 1980's showed a slight decrease in the overall prevalence of right-sided adenomas (6.4 per 1,000, 95% confidence limits 4.7-8.8 vs. 5.1 per 1,000, 95% CL 3.6-6.5), but a marked decrease occurred in left-sided adenomas (11.8 per 1,000, 95% CL 9.3-14.3 vs. 6.7 per 1,000, 95% CL 4.8-8.6). As a result, the ratio of right-sided to left-sided adenomas increased from 0.55 in the 1970's to 0.77 in the 1980's. This increased ratio occurred in both sexes, although prevalences were lower in females, and in whites. Unexpectedly, blacks had a ratio of right-sided to left-sided adenomas greater than unity in both the 1970's and 1980's (1.19 vs. 1.79) due to a relatively high prevalence of right-sided adenomas (5.8 per 1,000, 95% CL 3.6-8.0 in 1970's; 5.8 per 1,000, 95% CL 3.3-8.3 in 1980's), but low prevalences of left sided adenomas (4.9 per 1,000, 95% CL 3.0-6.8 in 1970's; 3.2 per 1,000, 95% CL 1.2-5.2 in 1980's). The overall adenoma prevalence in blacks was lower than in whites. We conclude that the right-sided predominance of colorectal adenomas in blacks suggests ethnic differences in the pathogenesis of colorectal adenomas. This observation may have important implications for secondary prevention of colorectal cancer. PMID- 1937953 TI - Inhibitory effect of maternal antibody on mother-to-child transmission of human T lymphotropic virus type I. The Mother-to-Child Transmission Study Group. AB - In order to evaluate the protective role of the maternal antibody against mother to-child transmission of HTLV-I, we followed a total of 780 children born to HTLV I carrier mothers by investigating the level of anti-HTLV-I antibody transferred in utero, decline of the maternal antibody and seroconversion in post-natal life. The anti-HTLV-I antibody was positively detected within the first 3-6 months of life and declined at 6-12 months after birth in all children. After the maternal antibody declined, seroconversion occurred in some of the children following either breast feeding or bottle feeding. The seroconversion rates of short-term (less than or equal to 6 months) and long-term (greater than or equal to 7 months) breast feeders were 4.4% (4/90 cases) and 14.4% (20/139 cases), and the rate of bottle feeders was 5.7% (9/158 cases). Long-term breast feeding yielded more seroconverters than short-term breast feeding; 14.4% (20/139 cases) vs. 4.4% (4/90 cases), RR = 3.68, p = 0.018. The seroconversion rate of short-term breast feeders was nearly equal to that of bottle feeders; 4.4% (4/90 cases) vs. 5.7% (9/158 cases), RR = 0.770, p = 0.471. When neonatal lymphocytes were cultured with breast milk cells of HTLV-I carrier mothers, the in vitro infection of HTLV I was inhibited by the addition of HTLV-I-seropositive cord-blood plasma. Our results suggest that the maternal antibody may inhibit HTLV-I infection by short term breast feeding but not by long-term breast feeding after decline of the maternal antibody. PMID- 1937954 TI - Cancer mortality in the USSR, 1986-88. AB - Mortality rates in the USSR for the major cancer sites have been computed for the period 1986-88 from official numbers of certified deaths and population estimates provided by the World Health Organization databank, and compared with rates for 26 other European countries. Among males, elevated mortality rates (age-adjusted, world standard) were observed for cancer of the oral cavity and pharynx (6.6/100,000), oesophagus (8.4/100,000) and larynx (6.8/100,000). Mortality from cancer of the stomach (38.4/100,000 males and 16.5/100,000 females, for a total of 87,000 deaths per year) was the highest in Europe. Likewise, overall lung cancer rates among males (61.0/100,000, for over 77,000 deaths per year) were among the highest in Europe, and showed substantial rises over the last 2 decades. Lung cancer mortality in females was comparatively low (6.9/100,000), and increased only moderately. Rates for cancers of the intestine (14.6/100,000 males and 10.6/100,000 females) and of the female breast (12.9/100,000) were comparatively low as compared to most other European countries, and those for prostatic cancer (5.9/100,000) were the lowest registered in Europe. In contrast, mortality for cancer of the uterus (9.7/100,000) was among the highest in Europe, probably due to high mortality from cervical cancer. Priorities for cancer control in the Soviet Union are thus reduction of consumption of tobacco and alcohol, which largely explain the high rates for lung and upper digestive and respiratory sites, improvements in diet composition and food storage to reduce the substantial excess of stomach cancer, and rational screening for cervical cancer. PMID- 1937955 TI - Expression of lactoferrin in human stomach. AB - The expression of the haeme-binding protein, lactoferrin, was studied in human gastric tissues displaying normal, benign hyperplastic or malignant histology. A single 2.5-kb mRNA was detected in only 14% (2/14) of normal resections. This was similar to the finding that 85% of tumours were also negative, with 4/27 positive. In contrast, samples with superficial or atrophic gastritis had a high frequency of expression, with 5/7 and 9/14 positive respectively. The higher incidence of lactoferrin mRNA in antral samples was a reflection of the greater proportion of these compared with body resections of patients with gastritis. No expression was seen in any of 5 gastric carcinoma cell lines. High levels were observed in the cardia, in contrast to complete absence in the oesophagus. Immunocytochemistry showed localization of lactoferrin in cells of both antral and body glands. Chief cells, but not adjacent parietal cells, were strongly stained. In tissues exhibiting superficial or atrophic gastritis we observed a greater degree and intensity of staining as compared with samples with normal histology. We also observed some staining of tumour cells, though this was very patchy. Lactoferrin may have a role in mucosal iron transport in both normal and highly proliferating tissue, but does not appear to be significantly associated with malignant lesions. PMID- 1937957 TI - Pentoxifylline enhances lung colonization and alters cell adhesion and glycosaminoglycan synthesis by metastatic B16 melanoma cells. AB - The effect of pentoxifylline on B16 melanoma cell lung colonization, synthesis and properties of glycosaminoglycans (GAGS), and adhesion to and degradation of subendothelial extracellular matrix was examined. Pentoxifylline inhibited cell growth, cell numbers being reduced by 50% following incubation for 4 days in the presence of 250 micrograms/ml pentoxifylline, while the treated cells appeared more flattened, possessed numerous but short dendritic processes, and exhibited greatly enhanced tyrosinase activity and melanin synthesis. Pentoxifylline treatment increased the cells' ability to colonize the lungs of syngeneic C57BL mice following tail-vein injection of 10(5) cells. The number of lung tumours increased from 16.7 +/- 6.1 to 52.2 +/- 17.8. In addition, pentoxifylline-treated cell GAG synthesis was reduced by 36%, and the charge density of chondroitin sulphate reduced, while tumour-cell aggregation and adhesion to subendothelial extracellular matrix was increased, as was the tumour-cell-mediated release of 35SO4 from radiolabelled subendothelial matrix. The observed changes in GAG synthesis may contribute toward the increased cell adhesiveness which, in addition to increased degradation of certain components of the subendothelial extracellular matrix, may account, at least in part, for the enhancement of lung colonization. PMID- 1937956 TI - Synergistic cytotoxicity of different alkylating agents for epithelial ovarian cancer. AB - Alkylating agents have been used individually and in combination to treat epithelial ovarian carcinoma. In this study, the cytotoxicity of 7 alkylating agents has been measured using a serial dilution clonogenic assay. When individual agents were evaluated, markedly different activity was observed against several ovarian cancer cell lines. Among 4 cell lines tested, OVCA 432 was the most sensitive to cisplatin, thiotepa and melphalan. When alkylating agents were used in combination against OVCA 432, synergistic activity was observed with cisplatin and each of several other alkylating agents including thiotepa, melphalan, 4-hydroperoxycyclophosphamide (4HC) and carboplatin. The combination of cisplatin and thiotepa also exerted synergistic activity against the OVCA 420, 429 and 433 cell lines, but had only additive or subadditive activity against the NIH:OVCAR-3 cell line. Sequential treatment of tumor cell lines with the different alkylating agents was as effective as simultaneous treatment. Synergistic anti-tumor activity in cell culture is consistent with clinical observations that alkylating agents in combination appear more effective than single agents for treatment of advanced epithelial ovarian cancer. In addition, our study suggests that cisplatin in combination with thiotepa, 4HC or melphalan might prove useful for high-dose therapy with autologous bone-marrow support. PMID- 1937958 TI - Adaptation to 5-fluorouracil of the heterogeneous human colon tumor cell line HT 29 results in the selection of cells committed to differentiation. AB - The HT-29 cell line contains a small proportion of differentiated polarized, enterocytic and mucus-secreting cell types (less than 95%) which can be selected under various pressure conditions, e.g., glucose deprivation or methotrexate. The purpose of the present work was to investigate whether this also applies to 5 fluorouracil (FUra). Stepwise adaptation of exponentially growing cells to 1, 5, 10 and 20 microM FUra results, after a phase of high mortality, in the emergence of adapted sub-populations with stable growth rates and curves, and IC50 6, 18, 37, and 110 times higher than in untreated cells respectively. FUra-adapted cells are all differentiated, according to 2 phenotypes: (I) polarized dome-forming cells which express carcinoembryonic antigen at their apical surface and (2) goblet cells which secrete a mucus of colonic immunoreactivity. These phenotypes are present in the parental population and are different from those selected e.g., by glucose deprivation or methotrexate. This differentiation pattern is maintained when the cells are subcultured in drug-free medium. Resistance to FUra is acquired through gene amplification as substantiated by a 4- to 6-fold increase of thymidylate synthase gene copies in cells stably adapted to the drug. Whether the same mechanism or others are responsible for the first steps of resistance to FUra remains to be elucidated. Altogether, these results support the hypothesis that some of the cells which are present in the parental line and are committed to differentiation possess advantages which allow them to immediately resist and secondarily adapt to FUra. Comparison of the differentiation characteristics of FUra-adapted cells with those from cells selected under other pressure conditions suggests that resistance and adaptation to either type of pressure may depend on the differentiated phenotype to which the cells are committed. PMID- 1937959 TI - Increased growth adaptability to 5-fluorouracil and methotrexate of HT-29 sub populations selected for their commitment to differentiation. AB - Adaptation of the heterogeneous human colon carcinoma cell line HT-29 to lethal concentrations of methotrexate (MTX) and 5-fluorouracil (FUra) was shown to result in the emergence of sub-populations of cells all stably committed to differentiation. It was postulated that these populations result from selection of a few cells present in the parental line which possess, associated with their ability to differentiate, particular advantages allowing them to adapt to adverse conditions such as MTX or FUra. The purpose of the present study was to further verify this hypothesis by investigating whether HT-29 sub-populations selected for the commitment of all cells to differentiation would spontaneously be more resistant and adaptable than the parental cells to MTX and FUra. This study included a mucus-secreting clone (HT29-16E), a transporting clone (HT29-19A), and an enterocytic population selected by glucose deprivation (HT29-Glc-/+). Although all 3 populations show only a slight increase in their spontaneous resistance to both drugs, as substantiated by the values of IC50 which are only less than 2 fold higher than in parental cells, they are more adaptable as judged by growth curves, over a 50-day culture period, under exposure to 1 microM FUra and 0.1 microM MTX. In sharp contrast to parental cells, which, at these concentrations, show a high rate of mortality, all 3 populations, although growing slowly, reach densities more or less close, depending on the drug and population concerned, to that of control untreated cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937960 TI - Active oxygen transforms murine myeloid progenitor cells in vitro. AB - Active oxygen (AO) is ubiquitous in nature and its many forms can act as natural carcinogens. Their effect on the transformation of a mouse myeloid progenitor cell line was studied using anchorage-independent colony formation in methylcellulose as the primary assay. Both cytotoxic and non-toxic concentrations of t-butylhydroperoxide, hydrogen peroxide and menadione were examined. At non cytotoxic concentrations, no AO transformation of these cells from interleukin-3 dependence to factor independence (FI) was observed, even after as many as 25 treatments. At cytotoxic concentrations, however, all 3 classes of AO transformed the cells to FI growth. The most potent agent was t-butyl hydroperoxide (43-fold induction), followed by hydrogen peroxide and then menadione. As little as one exposure to cytotoxic levels of these oxidants induced significant transformation, with relative potencies the same as those observed for multiple exposures. These inductions were not due to general cytotoxic effects, since sodium fluoride and heat-shock treatment gave minimal inductions. AO-induced colonies in methylcellulose that were removed, examined and then injected into pre-irradiated mice uniformly produced tumors. Control, non-treated cells did not form tumors. Tumorigenic cells did not form colonies in methylcellulose at lower plating densities. Furthermore, low numbers of transformed cells supplemented to high density with normal cells showed a small but insufficient increase in colony number as compared with high-density cultures of transformed cells. Our results suggest that the transformants depend upon a paracrine mechanism of growth that is mediated by the transformed cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937961 TI - Human tumor spontaneous metastasis in immunosuppressed newborn rats. II. Multiple selections of human melanoma metastatic clones and variants. AB - Using a recently developed model of human tumor spontaneous metastasis in immunosuppressed newborn rats, we selected variants with different metastatic abilities from the human melanoma cell line M4Be. We used 4 in vivo selection approaches, by direct serial tumor transplantations or by techniques involving in vitro reculture of the cells recovered from s.c. tumors or lung and lymph-node metastases. In addition, 3 series of clones were derived in vitro from the M4Be cell line, either by limiting-dilution or by cloning in semi-solid agar and harvesting small and large colonies. A considerable amount of heterogeneity in tumorigenicity and metastatic ability was demonstrated among variants and clones following in vivo selections and in vitro cloning. Four main malignant phenotypes were identified among those expressed by the selected cells: poorly tumorigenic and poorly metastatic; poorly tumorigenic and highly metastatic; highly tumorigenic and poorly metastatic; and highly tumorigenic and highly metastatic. However, while malignant phenotype (i.e., tumorigenicity and metastatic ability) did not appear to be grossly influenced by in vitro cloning procedure, it appeared greatly influenced both by the in vivo selection procedure (direct transplantations or use of in vitro culture between the in vivo passages) and by the origin of the cells under selection (s.c. tumor or metastases). Our study provided us with a large panel of variants and clones with varying metastatic abilities, which represent a model of human melanoma spontaneous metastasis allowing the study of critical determinants in human tumor metastasis. PMID- 1937962 TI - The role of alkaline reflux in esophageal carcinogenesis induced by N-amyl-N methylnitrosamine in rats. AB - It is now accepted that the incidence of esophageal carcinoma is highest in the middle thoracic region. Esophageal carcinoma after gastrectomy, however, has a tendency to develop in the lower thoracic region. These studies suggest a possible correlation between the development of esophageal carcinoma and gastrectomy, i.e., alkaline reflux into the esophagus. To elucidate this correlation, the role of alkaline reflux of duodenal contents in the development of esophageal squamous-cell carcinoma induced by N-amyl-N-methylnitrosamine (AMN) was investigated in Wistar rats. The animals were divided into 3 groups; gastrectomized rats with or without regurgitation of duodenal contents into the esophagus, and control rats without gastrectomy. All received low doses of AMN for 8 weeks and were subsequently killed for pathological examination. Esophageal squamous-cell carcinomas were found only in gastrectomized rats with regurgitation. The carcinomas were found exclusively in areas of reflux esophagitis and were accompanied by severe dysplasia. Our results indicate that alkaline reflux of duodenal contents strongly contributes to the development of esophageal squamous-cell carcinoma. PMID- 1937963 TI - Interferon-gamma interrupts autocrine growth mediated by endogenous interleukin-6 in renal-cell carcinoma. AB - Cells of the renal-cell carcinoma line ACHN constitutively produce IL-6, express the IL-6 receptor and use IL-6 in an autocrine fashion to augment their growth. Growth arrest of ACHN cells can be achieved by exposure of cells to neutralizing monoclonal antibody (MAb) to recombinant human (rh) IL-6. Treatment of ACHN cells with rh IFN-gamma also leads to inhibition of proliferation of these cells in a dose-dependent manner, that can be reversed by exogenous rh IL-6, while IFN alpha, IL-2, IL-4 and vinblastine or 17-beta-estradiol has no effect on growth (3H-thymidine uptake) of ACHN cells and IL-6 expression. Studies on the mechanism of action of IFN-gamma revealed that IFN-gamma was acting by inhibiting the autocrine IL-6-mediated loop generated by ACHN. PMID- 1937964 TI - The lipoxygenase metabolite 12(S)-HETE induces a cytoskeleton-dependent increase in surface expression of integrin alpha IIb beta 3 on melanoma cells. AB - Integrin receptors are mediators of cell-extracellular matrix and cell-cell interactions. Biochemical and immunocytochemical evidence shows that the platelet integrin receptor alpha IIb beta 3 is present on the cell surface, at focal adhesion plaques and in the perinuclear region of metastatic B16a murine melanoma cells. Antibody to the fibronectin receptor alpha 5 beta i, inhibits basal adhesion by approx. 30%, whereas antibodies to alpha IIb beta 3 are ineffective. The surface immunoreactivity of tumor cells for alpha IIb beta 3 can be enhanced by pre-treatment (5 min) with a lipoxygenase metabolite of arachidonic acid [i.e. 12-(S)-HETE] in a dose-dependent manner (max. effect approx. 0.1 microM). Other lipoxygenase metabolites are ineffective. B16a cells possess a large intracellular pool of alpha IIb beta 3, from which the receptor complex translocates to the cell surface following 12-(S)-HETE pretreatment. This pre treatment of tumor cells enhances their adhesion to fibronectin, which is mediated exclusively by alpha IIb beta 3 receptors. 12-(S)-HETE also facilitates the redistribution of alpha IIb beta 3 in the plasma membrane with localization at the focal adhesion plaques. The cytoskeleton of the B16a cell is characterized by an absence of distinct microtubules in interphase cells and the presence of prominent microfilaments and vimentin intermediate filaments. In B16a cells, the disruption of intermediate filaments and/or microfilaments prevents the 12-(S) HETE-induced increase in plasma membrane alpha IIb beta 3 and enhanced tumor-cell adhesion to fibronectin. The microtubule-disrupting agent, colchicine, is ineffective in both respects. We conclude that the lipoxygenase metabolite of arachidonic acid, 12-(S)-HETE, regulates the surface expression and function of the alpha IIb beta 3 integrin in B16a cells. Further, these data support the hypothesis that microfilaments and intermediate filaments have a profound role in regulating the expression of a multifunctional integrin in B16a tumor cells. PMID- 1937965 TI - Modulation of tumoricidal activity, induced in bone-marrow-derived mononuclear phagocytes by interferon gamma or Corynebacterium parvum, by interferon beta, tumor necrosis factor, prostaglandin E2, and transforming growth factor beta. AB - Among a series of agents, including various interleukins and growth factors, only interferon gamma (IFN gamma) and heat-killed Corynebacterium parvum (CP) organisms were able to elicit, within 24 hr, tumoricidal activity in bone-marrow derived mononuclear (BMM) phagocytes. In subsequent experiments, the abilities of interferon beta (IFN beta), tumor necrosis factor alpha (TNF alpha), prostaglandin E2 (PGE2), and transforming growth factor beta (TFG beta), alone or in combinations of 2, to modulate tumoricidal activity triggered in BMM phagocytes by IFN gamma or CP, were compared. In concentrations secreted by macrophages under physiological conditions, these agents proved potent in modulating induction and/or expression of tumoricidal activity. However, their ability to interfere with tumoricidal activity varied considerably, depending on the extent of macrophage differentiation and/or functional responsiveness, the pathway of macrophage activation, the type, concentration and combination of the macrophage secretory molecules, and on whether the agents were present during induction and expression or only during expression of tumoricidal activity. In showing that IFN beta and TNF alpha were mostly enhancing and TGF beta mostly suppressive, whereas PGE2 suppressed induction but enhanced expression of tumoricidal activity, our findings provide further support for the concept that these macrophage-derived molecules have a key role in autocrine regulation of macrophage functional activities. PMID- 1937966 TI - On JUMBO and "Junkie" trials. A fumbled affair, a jungle, or the ultimate solution? PMID- 1937967 TI - Beat-to-beat variation of heart rate in diabetic patients with autonomic neuropathy and in completely cardiac denervated patients following orthotopic heart transplantation. AB - Dysfunction of the vagal nerve, an early symptom in the development of autonomic neuropathy, can be assessed reliably by the beat-to-beat variation in heart rate. Patients after a cardiac transplantation are a unique model to investigate the beat-to-beat variation of a completely denervated heart. Heart rate and the beat to-beat variation during normal and deep respiration were investigated in diabetic subjects with an autonomic neuropathy (n = 10), age and sex matched healthy controls (n = 10) and cardiac transplanted patients (n = 10). Further studies during pharmacological blockade of the parasympathetic nervous system with atropine were performed. In the denervated heart the coefficient of variation of the beat-to-beat interval was 0.38 +/- 0.02% during normal respiration, compared to 1.32 +/- 0.13% (P less than 0.0001) and 2.56 +/- 0.13% (P less than 0.0001) in the diabetic and control subjects, respectively. Administration of atropine (2 mg intravenously) decreased the coefficient of variation of the RR-interval to 0.73 +/- 0.09% in the diabetic patients (P less than 0.0005) and to 0.67 +/- 0.07% in the controls (P less than 0.0001), whereas the coefficient of variation remained unaffected in the cardiac denervated patients (0.39 +/- 0.02%). In the three groups an almost parallel increase of the RR-variation was observed during deep respiration at a rate of 6 breaths/min (from 0.38 +/- 0.02% to 1.99 +/- 0.38% in cardiac transplanted patients, P less than 0.0025; from 1.32 +/- 0.13% to 3.10 +/- 0.43% in diabetic patients, P less than 0.0025; from 2.56 +/- 0.13% to 5.42 +/- 0.94% in healthy controls, P less than 0.005). We conclude that a beat-to-beat variation of heart rate is present in the completely denervated heart. This RR-variation can not be influenced by a pharmacological blockade of the parasympathetic nervous system with atropine. The beat-to-beat variation increases during deep respiration not only in healthy controls but also in diabetic patients with autonomic neuropathy (partially denervated hearts) and cardiac transplanted patients (completely denervated hearts). This indicates an intracardiac mechanism in the modulation of heart rate. PMID- 1937968 TI - The role of aggregation of platelets in pregnancy-induced hypertension: a comprehensive and longitudinal study. AB - Plasma 6-keto-prostaglandin F 1 alpha and thromboxane B2, the metabolites of prostacyclin and thromboxane A2 respectively, were measured in 12 women with pregnancy-induced hypertension, 12 age-matched normotensive pregnant women and 8 non-pregnant women as controls. Pregnancy was divided into 3 stages, namely: 22 27, 28-32 and 33-39 weeks. The concentrations of thromboxane B2 in the plasma of women with pregnancy-induced hypertension was 1.4-1.7 times greater than normotensive pregnant subjects at the same gestational stage, and 2 times higher than controls. Plasma levels of 6-keto-prostaglandin F 1 alpha in normotensive pregnant women was 1.8 times greater than in those with pregnancy-induced hypertension at 28-32 and 33-39 weeks, and was significantly higher than control. The ratio of thromboxane B2 to 6-keto-prostaglandin F 1 alpha was markedly increased in the group of patients with pregnancy-induced hypertension at 28-32 and 33-39 weeks gestation. The ratio of the two metabolites in normotensive patients at each stage of gestation was similar to the control group. The ratio of circulating aggregated platelets in subjects with pregnancy-induced hypertension was significantly lower than in normotensive pregnant subjects at 33 39 weeks, implying increased turnover of platelets in pregnancy-induced hypertension. There was no significant difference in count of platelets, adenosine diphosphate threshold concentration and variables of platelet aggregation induced by adenosine diphosphate among the 3 groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937969 TI - Left atrial clot in patients with mitral prostheses: increased rate of detection after recent systemic embolism. AB - We studied 70 patients with mitral valvar replacements by both transthoracic and transoesophageal echocardiography. Fifteen subjects had recently suffered a suspected embolic episode. The remainder (55) were studied for other clinical reasons. Transthoracic echocardiography demonstrated thrombus in only 1 of the 70 patients. By contrast, transoesophageal examination revealed thrombus in 8 out of 15 patients with recent suspected embolism and 3 out of 55 without. Thrombus was most commonly seen in patients with biological valvar prostheses whose anticoagulation had been discontinued. When patients with prosthetic mitral valves present with a suspected embolic episode, transoesophageal echocardiography is strongly recommended. This study also suggests that transoesophageal echocardiography may be useful for evaluating patients with biological valves if anticoagulation is withdrawn so as to identify formation of thrombus at the earliest possible stage. PMID- 1937970 TI - The relation between radionuclide angiography and Doppler echocardiography during contractile changes with infusions of epinephrine. AB - To define the quantitative relations between radionuclide and Doppler measures of systole during sympathetic activation with epinephrine, 10 young normal men were studied with simultaneous radionuclide angiography and M-mode and Doppler echocardiography during graded infusions of epinephrine (10, 25 and 50 ng/kg/min for 12 minutes each). During a nine-fold increase in circulating levels of epinephrine in arterialized plasma (94 +/- 59 to 879 +/- 310 pg/ml, P less than 0.001), the heart rate increased from 58 +/- 8 to 73 +/- 7 beats/min (P less than 0.01), whereas the mean arterial pressure fell from 82 +/- 3 to 75 +/- 6 mmHg (NS) and end-systolic wall stress decreased from 97 +/- 6 to 67 +/- 10 dynes/sec (P less than 0.01). The ejection fraction as estimated using radionuclide techniques increased from 68 +/- 6 to 83 +/- 6%, the peak ejection rate measured in this way increased from -3.36 +/- 0.3 to -5.10 +/- 0.5 end-diastolic volumes/sec, the ejection fraction as estimated with M-mode echocardiography increased from 66 +/- 5 to 83 +/- 5%, the echocardiographic ventricular dimension shortening increased from -1.78 +/- 0.2 to -2.7 +/- 0.4 sec-1, the peak aortic outflow velocity as measured with Doppler techniques increased from 98 +/- 13 to 147 +/- 25 cm/sec, and the aortic outflow acceleration velocity increased from 11 +/- 3 to 27 +/- 7 m/sec2 (all P less than 0.001). There was a significant correlation between the changes in radionuclide and M-mode estimations of ejection fractions (r = 0.82), between the radionuclide peak ejection rate and M mode peak dimension shortening (r = 0.80) and between the radionuclide peak ejection rate and the Doppler peak aortic outflow velocity (r = 0.90) (all P less than 0.01). We conclude that corresponding radionuclide and Doppler echocardiographic measurements of systolic function are altered similarly during increased sympathetic activation with epinephrine. PMID- 1937971 TI - Coronary-cameral fistula in association with intracardiac tumour and aortic stenosis in an adult. AB - We present a patient with the unexpected association of left ventricular tumor, a fistula between the right coronary and the right atrium, and senile valvar aortic stenosis. He had anginal complaints. Doppler echocardiography revealed moderate aortic stenosis with mild aortic and moderate mitral regurgitation. A tumour was detected in the left ventricle. Selective coronary angiography disclosed normal anatomy with a fistula originating from the proximal right coronary artery and draining into the right atrium. He refused operative treatment and is still alive, 1 year after the diagnosis was made, without complications. PMID- 1937972 TI - Mid left anterior descending coronary artery originating from the right coronary artery. AB - Dual connection of the left anterior descending coronary artery to the left and right coronary arteries is a very rare congenital anomaly. In this report we describe two cases in which the mid-position of the left anterior descending coronary artery is connected to the right coronary artery, one directly and the second by way of the infundibular artery. To the best of our knowledge, connection of the mid-position of the left anterior descending to the infundibular artery has not been previously described. PMID- 1937973 TI - Astemizole-induced ventricular arrhythmias: an unexpected cause of convulsions. AB - Antihistamines are commonly used drugs. The more recent additions to the formulary are less sedative, but have been implicated as a cause of ventricular arrhythmias. We report a case in which a deliberate overdose of astemizole was associated with Mobitz type two heart block and prolongation of the QT interval, causing the so-called torsade-de-pointes ventricular tachycardia. PMID- 1937974 TI - Transatrial repair of ventricular septal defect subsequent to myocardial infarction. AB - We describe successful transatrial repair of a ventricular septal defect occurring secondary to myocardial infarction. This approach avoids the need for ventriculotomy and may be technically simpler and safer than repair across the zone of infarction in a subset of patients with posterior defects and right ventricular dysfunction who survive the early period subsequent to their infarct. PMID- 1937975 TI - Ebstein's malformation of the tricuspid and mitral valves associated with hypoplasia of the ascending aorta. AB - The clinical and morphological features of Ebstein's malformation were well defined many years ago. This report analyses the clinical and morphological aspects of an unusual case which presented Ebstein's malformation of both the tricuspid and mitral valves in association with hypoplasia of the ascending aorta. PMID- 1937976 TI - Echocardiographic diagnosis of infective endocarditis of all four cardiac valves. AB - Cross-sectional echocardiography in a 78-year-old woman with infective endocarditis demonstrated echogenic masses on all four cardiac valves. The echocardiographic diagnosis was confirmed at autopsy. PMID- 1937977 TI - Diaphragmatic hernia with extrathoracic heart. AB - We report the cross sectional ultrasonic diagnosis of a rare form of central diaphragmatic hernia. The inferior portion of the parietal pericardium was also absent, with herniation of the heart through the defect. Surgical repair was successfully undertaken based on the ultrasonic findings. PMID- 1937978 TI - Hypertension to normotension? A case of 'summer-salt'. PMID- 1937979 TI - Coronary angioplasty via saphenous vein grafts. AB - Percutaneous transluminal angioplasty of coronary stenoses distal to anastomosis of a venous graft was attempted through the graft 22 times in 19 patients. Ten patients had stable angina, seven unstable angina and two patients acute myocardial infarction. The mean interval between bypass surgery and angioplasty was 6.5 years (range 1-15). Fifteen lesions were dilated in the left anterior descending artery, five in the right coronary artery, and two in the circumflex artery. Three procedures were for double lesions. In two cases, a stenosed vein graft was also dilated. All grafts were cannulated with an El Gamal guiding catheter. The procedure failed in two cases. The remaining 20 lesions were successfully dilated. Early and late occlusion of the graft occurred in one patient, and coronary arterial stenosis recurred in two patients. All three patients underwent successful redilatation. The 17 patients undergoing successful dilatation were asymptomatic, with a normal exercise test and/or maintained angiographic result at follow-up of 14 months mean duration (range 2-48). Angioplasty of coronary stenosis through a vein graft is feasible, safe and effective. This therapeutic approach avoids the need for repeat bypass surgery and, as judged by long-term follow-up, has a favourable clinical outcome. PMID- 1937980 TI - Right ventricular volumes determined by computerized thermodilution in ischaemic heart disease: effect of exercise and nitroglycerin. AB - In 29 patients with stable ischaemic heart disease, right heart catheterization was performed to assess the effect of exercise and nitroglycerin on right ventricular volumes, which were determined by a new computerized thermodilution system. The coefficient of variation for the determination of right ventricular ejection fraction averaged 11.0 +/- 6.2% (mean +/- standard deviation) at rest and 14.6 +/- 8.1% during exercise. End-diastolic volume index increased from 90 (65-127) ml/m2 [median (range)] at rest to 101 (81-130) ml/m2 (P less than or equal to 0.0001) during exercise. Nitroglycerin reduced this parameter at rest to 77 (44-121) ml/m2 (P less than or equal to 0.05), without affecting exercise values. Resting right ventricular ejection fraction (55 [44-64]%) was diminished by both exercise (to 52 [39-62]%, P less than or equal to 0.05) and nitroglycerin (to 53 [40-65]%, P less than or equal to 0.05). Additionally, nitroglycerin reduced the exercise induced decrease of right ventricular ejection fraction from -3 (-20-10)% to -1 (-15-14)% (P less than or equal to 0.01). Nitroglycerin diminished the left-to-right interventricular end-diastolic pressure gradient, which was estimated from the difference between pulmonary capillary wedge pressure and right atrial pressure, at rest from 6 (1-17) mmHg to 5 (2-14) mmHg (P less than or equal to 0.05) and during exercise from 17 (6-31) mmHg to 14 (1 33) mmHg (P less than or equal to 0.001). It is concluded, that both exercise and nitroglycerin cause significant changes in right ventricular volumes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937981 TI - The effect of calcitonin gene-related peptide on arrhythmia caused by adenosine diphosphate and desacetyldigilanide-C in rats. AB - We investigated the effect of calcitonin gene-related peptide on the arrhythmia induced by two drugs in rats. The results of our experiments have proved that calcitonin gene-related peptide could reduce the degree of atrioventricular block, protect against the attacks of sinus standstill and ventricular fibrillation produced by adenosine diphosphate, and improve restoration of sinus rhythm. Calcitonin gene-related peptide was able to eliminate sinus standstill and ventricular fibrillation resulting from administration of desacetyldigilanide C. These results demonstrate that calcitonin gene-related peptide has strong antiarrhythmic effects in experimental animals. PMID- 1937982 TI - Effects of fibric acid derivatives on accumulation of actin in myocardiocytes. AB - We used sodium dodecylsulphate polyacrylamide gel electrophoresis and immunoblotting to analyze the effects of the fibric acid derivatives bezafibrate, fenofibrate and gemfibrozil on the accumulation of actin in the cytoplasmic and cytoskeletal fraction of cultured myocardiocytes. All three drugs tested modified cellular and subcellular actin in different ways, and the findings are thought to be related with the secondary effect of arrhythmia known to be caused by these drugs. Bezafibrate and gemfibrozil more markedly affected accumulation of actin by myocytes, while fenofibrate interfered less notably with the accumulation of this protein. PMID- 1937983 TI - Morphogenetic considerations on congenital malformations of the outflow tract. Part 2: Complete transposition of the great arteries and double outlet right ventricle. AB - On the basis of our recent embryologic work concerning the separation process of the outflow tract, our study of the morphology of specimens from the Leiden Collection of malformed hearts, and in conjunction with our review of the literature, we have reconsidered the morphogenesis of complete transposition and double outlet right ventricle. In complete transposition, a mirror-image arrangement of the columns of the aorto-pulmonary septum could explain the discordant ventriculo-arterial connexion and might thus play a role in its development. Dedicating a cardinal role to the aorto-pulmonary septum in the morphogenesis of complete transposition does not, however, seem justified. Double outlet right ventricle is not an embryologic entity. From the stance of the embryologist, we prefer to consider double outlet right ventricle in terms of a feature that may occur in specimens related to hearts with either a concordant ventriculo-arterial connexion (such as tetralogy of Fallot, or the so-called Eisenmenger ventricular septal defect), or a discordant ventriculo-arterial connexion (complete transposition). PMID- 1937984 TI - Changes in plasma potassium during the dobutamine stress test. AB - We performed serial determinations of levels of potassium in 198 patients with suspected or proven coronary arterial disease who underwent a dobutamine stress test, so as to investigate if the depression in the ST segment induced by the test may be due to hypokalemia. The test consisted of an intravenous infusion of dobutamine, starting with a dose of 5 micrograms/kg/min for 5 minutes and continuing with 10, 15, 20 and up to 40 micrograms/kg/min every 5 minutes (mean peak dose = 20 micrograms/kg/min). Serial 12-lead electrocardiograms were taken to detect changes in the ST segment. The double product changed with dobutamine from 8844 +/- 6000 to 15201 +/- 3030. The peak dose of dobutamine induced a small but significant decrease in levels of serum potassium, with a further decrease 10 minutes later. In the 198 patients, the plasma potassium changes from 4.22 +/- 4.8 to 3.86 +/- 0.35 mmol/l (P less than 0.00001). The maximum decrease in potassium (0.56 +/- 0.49) occurred in the patients who received the highest dose of dobutamine (30 to 40 micrograms/kg/min). Only 17 patients reached levels lower than 3.5 mmol/l, and 4 of them achieved levels lower than 3.1 mmol/l. No correlation was found between depression of the ST segment equal to or greater than 1 mm on the electrocardiogram and the level of potassium after the test. No correlation was found between ventricular arrhythmias and levels of potassium. High doses of dobutamine, therefore, produce a small but significant decrease in potassium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937985 TI - Exercise cardiovascular responses to gallopamil in ischemic heart disease. AB - In a single-blind, placebo-controlled, crossover trial versus diltiazem, we evaluated the influence of gallopamil on cardiovascular responses evoked by bicycle exercise. Twelve patients with chronic stable angina were enrolled. After a 5 days placebo run-in period, patients were randomly assigned either to gallopamil (50 mg thrice daily) or diltiazem (60 mg thrice daily) for 10 days. Then, patients were changed to the alternative drug. After placebo, and at the end of each subsequent period, all subjects underwent right heart catheterization by means of a Swan-Ganz thermodilution catheter. Hemodynamics were determined in 3 ways: supine, standing and during a multistage exercise test. RESULTS: anginal attacks were reduced to a similar degree by gallopamil (2.1 +/- 1/week versus 5.8 +/- 2.8/week during placebo, p less than 0.01) and diltiazem (2.0 +/- 0.8/week versus 5.8 +/- 2.8/week during placebo, P less than 0.01). At rest, gallopamil caused a significant decrease in heart rate and a slight fall in systemic vascular resistance. Cardiac index rose during exercise and was higher with respect to placebo at peak exercise (6.7 vs 5.6 l/min/m2, P less than 0.05). As a consequence, stroke volume index and stroke work index both increased at maximum workload (P less than 0.05). Compared to placebo, exercise time was significantly improved by gallopamil (+50%, P less than 0.02) and diltiazem (+38%, P less than 0.05). Likewise, time to onset of ST-segment depression was prolonged by 70% with gallopamil (P less than 0.01) and by 64% with diltiazem (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937986 TI - Profile of right-sided endocarditis: an Indian experience. AB - The clinical profile of right-sided infective endocarditis in India was studied from a review of records of patients with infective endocarditis admitted to this hospital. From November 1982 to November 1989, 109 patients with infective endocarditis showed vegetations on cross-sectional echocardiography confirming the diagnosis of infective endocarditis. In 19 (17.4%) patients, only the right side of the heart was involved: specifically the tricuspid valve alone in 10; tricuspid and pulmonary valves in 4; tricuspid valve and right ventricular outflow tract in 1; tricuspid valve and right ventricular free wall in 1; pulmonary valve alone in 2; and bifurcation of pulmonary trunk in 1. Eleven patients (57.9%) had underlying congenital heart disease whereas the remaining 8 patients (42.1%) did not have any underlying heart disease. The latter group, therefore, had isolated right-sided infective endocarditis. Previous illnesses leading to isolated right-sided infective endocarditis were: puerperal sepsis in 4; septic abortion in 1; staphylococcal pneumonia in 2; and epididymoorchitis in one. Eight out of 11 patients with congenital heart disease did not report any previous illness. In the remaining 3, right-sided endocarditis followed cardiac surgery in one; dental extraction without prophylaxis in one; and pulmonary balloon valvoplasty in one. All patients with isolated right-sided infective endocarditis had features of septicaemia, but a murmur of tricuspid regurgitation was audible in only 4 (50%) of them. We conclude that, unlike western reports, the pattern of right-sided infective endocarditis in India is different. No drug addict with right-sided infective endocarditis was seen; puerperal sepsis and septic abortion were the commonest causes of isolated right-sided infective endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937987 TI - Coronary venous noradrenaline during coronary angioplasty. AB - Coronary venous and arterial noradrenaline concentrations were measured during percutaneous transluminal coronary angioplasty in 14 patients. Coronary venous noradrenaline did not increase significantly during balloon inflation but was increased during early reperfusion in patients undergoing left anterior descending angioplasty (n = 8), from 157 +/- 38 pg/ml to 295 +/- 94 pg/ml (P less than 0.05). Coronary blood flow, measured by thermodilution in 7 further patients during left anterior descending angioplasty, was 69 +/- 9 ml/min, decreased to 80 +/- 3% of basal flow during balloon inflation (P less than 0.01) and increased to 135 +/- 5% during early reperfusion (P less than 0.01). It was estimated using these results that cardiac spillover of noradrenaline did not change during occlusion of the left anterior descending artery, but increased almost 3-fold during early reperfusion. During the period of balloon inflations, there was a modest increase in overall sympathetic tone, as assessed by total noradrenaline spillover to plasma (400 +/- 77 ng/min to 473 +/- 87 ng/min, P less than 0.01). These results, suggesting an increase in release of noradrenaline during early reperfusion following brief occlusion of the left anterior descending artery, may be relevant to the genesis of reperfusion arrhythmias. PMID- 1937988 TI - Acute haemodynamic effects of dopexamine in patients with coronary arterial disease. AB - We assessed the acute haemodynamic effects of dopexamine 1 microgram/kg/min and 3 micrograms/kg/min in 21 patients with coronary arterial disease following routine catheterisation. Patients were aged 38 to 72 years and left ventricular ejection fraction ranged from 23 to 79%. Dopexamine was well tolerated in all patients except one in whom transient ventricular arrhythmias occurred with 3 micrograms/kg/min. No patient developed angina. Dopexamine increased cardiac index (2.6 +/- 0.4 to 3.2 +/- 0.1 (P less than 0.001) and 4.0 +/- 1.0 1/min/m2 (P less than 0.001), control to 1 microgram/kg/min and 3 micrograms/kg/min, respectively) and decreased systemic vascular resistance index (3356 +/- 1506 to 2318 +/- 809 (P less than 0.001) and 2252 +/- 1973 dyne.sec.cm-5/m2 (P less than 0.001], but did not affect systemic arterial, pulmonary arterial or right atrial pressure. Maximum positive dP/dt was increased (1294 +/- 324 to 1597 +/- 505 (P less than 0.001) and 2199 +/- 819 mmHg/sec (P less than 0.001] as was left ventricular stroke work index (44 +/- 20 to 51 +/- 21 (P less than 0.05) and 56 +/- 27 g.m/m2 (P less than 0.001) control to 1 microgram/kg/min and 3 micrograms/kg/min, respectively). Left ventricular end diastolic pressure fell with 3 micrograms/kg/min from 19.8 +/- 6.9 to 12.4 +/- 4.6 mmHg (P less than 0.05) in patients with preserved left ventricular ejection fraction (greater than 50%, n = 6), but not in those with impaired left ventricular ejection fraction (less than 50%, n = 15), otherwise the effects in these two subgroups were similar. We conclude that dopexamine has both inotropic and vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937989 TI - The role of expectancy in hypnotic hypermnesia: a brief communication. AB - Previous research has yielded equivocal evidence of hypnotic memory enhancement. The present experiment assessed the effects of expectancy and hypnotizability on recall for videotaped material under waking and hypnotic conditions. Ss (N = 138) were informed of hypnotic induction either before (expectancy condition) or after (no expectancy condition) watching a videotaped enactment of a crime and completing an initial waking recall test (RI). Both groups then underwent hypnotic induction, and completed the test again (R2). Ss' raw recall scores were significantly greater under hypnotic than waking conditions, but this hypermnesia was not evident when scores were corrected for mere increase in rate of responding. Ss expecting later hypnosis scored significantly higher than Ss with no such expectations, but again, this difference was not evident in corrected scores. Hypnotizability of Ss was, however, related to corrected recall, with high hypnotizable Ss displaying the greatest increase in rate of responding from R1 to R2. No evidence for the hypothesized "suppression effect" underlying hypnotic hypermnesia was found. PMID- 1937990 TI - Storytelling, hypnosis and the treatment of sexually abused children. AB - The present article describes an assessment and therapy program for sexually abused children using hypnotherapeutic techniques which center on storytelling. Storytelling presents the therapist with an opportunity to use comforting suggestions, symbolism, and metaphor to provide the emotional distance necessary to deal with the trauma of abuse. Hypnotherapy proceeds in a stepwise fashion from the building of a sense of safety and security; to imaginative sharing; to the introduction of reality events; to the final step of addressing complex emotional issues of loss, trust, love, and guilt brought about by the abuse. PMID- 1937991 TI - Guided imagery, hypnosis and recovery from head and neck cancer surgery: an exploratory study. AB - The value of a brief, preoperative hypnosis experience was explored with a sample of 36 head and neck cancer surgery patients. 15 patients volunteered for the experimental hypnosis intervention. 21 patients who received usual care (no hypnosis) were followed through their hospital charts and were used as a comparison group. Hypnotic intervention and usual care groups were comparable in terms of relevant demographic variables. Postoperative hospitalizations for the hypnotic intervention group were significantly shorter than for the usual care group. Within the hypnotic intervention group, hypnotizability was negatively correlated with surgical complications and there was a trend toward a negative correlation between hypnotizability and blood loss during surgery. Findings suggest that imagery-hypnosis may be prophylactic, benefitting patients by reducing the probability of postoperative complications and thereby keeping hospital stay within the expected range. Recommendations are presented for a controlled, randomized, clinical trial with a sufficiently large sample to provide the opportunity for statistical analysis with appropriate power. PMID- 1937992 TI - The nature of hypnotic performance following administration of the Carleton Skills Training program. AB - 30 low hypnotizable Ss were administered the Carleton Skills Training (CST) program, while 8 were assigned to a practice group. Prior to treatment, an attempt was made to facilitate training by altering the ecological conditions of the laboratory. All Ss were tested immediately after treatment, and trained Ss were retested after 5-7 months. Immediate training gains were large and were comparable in magnitude to those routinely found at Carleton University. In addition, (a) trained Ss responded comparably whether screened once or twice, (b) practice alone did not enhance hypnotic performance, and (c) natural high hypnotizable Ss obtained significantly larger Field Inventory of Hypnotic Depth (Field, 1965) scores than created high hypnotizables. Follow-up scores fell between scores posted at screening and immediately after training. Current findings are interpreted in the context of existing evidence concerning the CST program. PMID- 1937993 TI - Pharmacokinetics and pharmacodynamics of two commercial oral nifedipine products. AB - Nifedipine, a calcium channel blocker, is widely used in the management of hypertension, angina and cardiac arrhythmias. In this study, the bioequivalence of two pharmaceutical formulations of nifedipine, Nifecard (10 mg capsules) manufactured by Dar Al-Dawa Development and Investment Co, Ltd. and Adalat (10 mg capsules) manufactured by Bayer Pharmaceutical Company, was assessed in twelve healthy male subjects. Nifecard or Adalat was given orally on two occasions separated by one week wash-out interval. Blood samples for the determination of plasma nifedipine concentration were taken for 8 hours following drug administration. Blood pressure and pulse were also measured after each treatment. Plasma nifedipine concentrations were measured by a simple, sensitive and reproducible HPLC method. There were no significant differences in oral absorption, Cmax, tmax, t1/2 and AUC between Nifecard and Adalat. Also, Nifecard and Adalat produced similar hemodynamic profiles (blood pressure and pulse). In conclusion, our results demonstrate that both Adalat and Nifecard are bioequivalent and produced similar pharmacological effects. PMID- 1937994 TI - Interferon therapy for basal cell carcinoma and squamous cell carcinoma. AB - Totally 161 basal cell and squamous cell carcinoma (BCC, SCC) patients were treated with human natural leucocytic interferon (HNLI) and recombinant IFN alpha 2c. After HNLI treatment, 61 out of 86 BCC patients and 29 out of 45 SCC patients were cured according to histopathologic and clinical findings. In 13 BCC and 13 SCC patients, the cancer lesion was reduced 25%-90%. After recombinant IFN alpha 2c treatment, 14 of 20 BCC patients and 4 of 10 SCC patients were cured according to histopathologic and clinical findings. In 6 BCC patients and 5 SCC patients the cancer lesion was reduced 25% to 90%. Both types of interferons are effective in the treatment of BCC and SCC patients. Local application of interferon stimulates immune reaction at the site of the tumor. There is a marked difference between the spontaneous macrophage activity and that induced by interferon. The interferon activated macrophages are significantly larger, the number of lysosomes and the density of macrophages is increased. In difficult locations intralesional therapy can be considered to avoid disfigurement of the patients with or without surgery. PMID- 1937995 TI - Prophylactic administration of ranitidine after sclerotherapy of esophageal varices. AB - The present trial was carried out to determine the usefulness of H2-receptor antagonist drug therapy for the prevention of esophageal bleeding and esophageal varices in patients who underwent sclerotherapy. According to randomization, out of the 58 patients, 28 received, along with the usual standard therapy, ranitidine and 30 received placebo. Ranitidine, 50 mg, was administered intravenously over a period of 3 days every 8 hours, and then 150 mg of ranitidine was given per os in the evening for one month. For improvement of hemostasis and during the elective sclerotherapies, 1% polidocanol was used as the sclerosant. During each puncture, 2 ml was injected. Injections were paravasal and intravasal. After sclerotherapy, endoscopic examinations were carried out on the third day and one month later. Necrosis was noted in 42% of the patients and esophageal mucosal inflammation in 26%. Esophageal ulcers did not occur. There was no statistically significant difference between the two groups in terms of age, sex ratio, cause of liver cirrhosis, and the Child's classification. The size of the esophageal varices had no effect on the development of esophageal mucosal changes in correlation with the quantity of sclerosant. The comparison of the two groups of patients, sclerosed for hemorrhage and sclerosed electively, showed no statistically significant difference regarding esophageal mucosal changes. No differences between the ranitidine and placebo groups of patients were observed in this indication. It can be concluded that esophageal mucosal changes probably arise as a consequence of the sclerosant, its concentration, quantity and mode of application.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1937996 TI - The distribution of ciprofloxacin and its metabolites in human plasma, pulmonary and bronchial tissues. AB - The disposition of ciprofloxacin and its pharmacologically active metabolites (sulfociprofloxacin, oxociprofloxacin, and desethylenciprofloxacin) in plasma, lung and bronchial tissues was studied in 24 patients undergoing a partial or total resection of the lung. The patients were divided into four groups, a control group and groups in which ciprofloxacin (200 mg) was given i.v. 1, 2 and 3 h before surgery. The concentrations of ciprofloxacin and its metabolites were determined by high performance liquid chromatography (HPLC). Ciprofloxacin concentrations in lung tissue were four times and in bronchial tissue twice those in plasma (p less than 0.01). The individual tissue concentrations of ciprofloxacin correlated with the individual plasma concentrations (r = 0.95 for lung; r = 0.94 for bronchi; p less than 0.001). Metabolite concentrations in both tissues and plasma were 10- to 100-fold lower than the concentrations of ciprofloxacin. These data suggest that the concentrations of the parent compound are essential for the therapeutic efficacy of ciprofloxacin. PMID- 1937997 TI - A study relating to bioavailability and renal elimination of bismuth after oral administration of basic bismuth nitrate. AB - The extent to which bismuth is absorbed following single and multiple oral administration of basic bismuth nitrate was investigated in healthy male subjects. The blood concentration of bismuth and the amounts excreted in urine and feces were determined. The results show that only a small fraction of the administered bismuth dose given in this form is absorbed. Existing differences in the absorption kinetics between this relatively insoluble bismuth salt and colloidal bismuth citrate are discussed. PMID- 1937999 TI - Antimicrobial drug use in urology. AB - Antimicrobial drug utilization patterns were studied on patients in the Urology Ward of Nehru Hospital attached to the Postgraduate Institute of Medical Education and Research, Chandigarh. The study was done over a six-month period in which antimicrobial prescription for all patients admitted under urology services were monitored and followed. There were 57 cases of benign hypertrophy of the prostate, 40 of urinary calculi and 20 each of congenital malformation, malignancies, strictures and other conditions. Gentamycin and cotrimoxazole were the most frequently used antimicrobials, as calculated by the DDD/100 bed days. PMID- 1937998 TI - Clinical and biological evaluation of dilevalol vasodilating properties in mild to moderate hypertension. AB - Dilevalol is a vasodilating beta-blocker with proven antihypertensive activity. In this study, 28 patients with mild-to-moderate uncomplicated hypertension underwent 2 submaximal exercise tests, each consisting of progressive steps of 20 watts for 2 minutes or up to 85% theoretical maximum heart rate. Five minutes after the first test, patients received either placebo or dilevalol 200 mg, 400 mg or 600 mg. The second exercise test was performed 3 hours later. Diastolic blood pressure, systolic blood pressure, heart rate and norepinephrine plasma levels were assessed before and after exercise. Dilevalol at all doses caused a significant decrease in heart rate and blood pressure both at rest and during exercise, compared to placebo. Dilevalol 600 mg had a greater effect on diastolic blood pressure than dilevalol 200 mg and 400 mg. Administration of dilevalol 200 mg and 400 mg enabled 42% of patients to increase their maximal exercise level by 20 to 60 watts. Dilevalol increased plasma norepinephrine levels at the 100 watts exercise levels from 5.1 +/- 4.0 nmol/l to 7.6 +/- 4.3 nmol/l (p less than 0.05). No adverse effects were observed during dilevalol treatment. This study shows that dilevalol is an effective antihypertensive agent that blunts heart rate and blood pressure risings during exercise. PMID- 1938000 TI - Pharmacokinetics of prednisone and prednisolone in bullous pemphigoid patients. AB - The purpose of this prospective study was to attempt to evaluate a possible relationship between corticosteroids pharmacokinetics parameters and clinical efficacy in bullous pemphigoid (BP) patients. Sixteen BP patients took part in the study. Prednisone (Cortancyl, Laboratoire Roussel) was given orally (1 mg/kg/day) in a single morning dose. Eleven blood samples were collected over 24 h for the pharmacokinetic studies on day 1 (first day of treatment) and on day Y (after the clinical evaluation). Efficacy was evaluated as the number of new skin blisters on day 1 and on day X which was either the day of cure, i.e. no blisters (responders), or the day of treatment failure, i.e. persistence of blisters (non responders). Prednisolone (PO) was assayed using high-performance liquid chromatography (HPLC). Areas under the plasma concentration time curves (AUC) and plasma half-lives were estimated using a model independent approach. In responder patients, PO AUC values were 6,225.5 +/- 575.5 ngh/ml, range 3,933-9,080.5 on day 1 and 5,687 +/- 535 ngh/ml, range 4,513.5-9,828.5 on day Y. There was a significant correlation (0.87) between the number of skin blisters on day 1 and the time required for their resolution. The pharmacokinetics and clinical data suggest that a "therapeutic" AUC value was necessary to achieve clinical efficacy and that the duration of treatment depended on the number of blisters on day 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938001 TI - The Yugoslavian drug addict's family structure. AB - The objective of this paper was to investigate the characteristics of a drug addict's family structure in our culture. The investigation, involving 41 families, was performed by using a three-generational genogram and an interview. The "identified patient" was addicted to opiates. The results show that the family of a drug-addicted individual does not differ much, if at all, from the typical post-war Yugoslav family. However, the feedback and interactions of certain positions in the birth order of IPs and their parents, together with some other factors, point to some predictable risk factors for the onset of drug addition. PMID- 1938002 TI - Smoking and health: a review prepared by the Smoking and Health Subcommittee of the Tobacco Industries Council, a council formed by the Minister of Finance of Japan. AB - Any definition of health is inevitably broad and contains various elements that may differ from one individual to another. Recent studies on the effects of smoking on physical and mental health have progressed remarkably and have great value in the fields of epidemiology, pathology, clinical medicine, and psychiatry. This report concludes that while smoking may have beneficial psychological effects on smokers, it may pose a risk to physical health. PMID- 1938003 TI - Effect of psychological factors on risk behavior of human immunodeficiency virus (HIV) infection among intravenous drug users (IVDUs). AB - The effect of psychological factors on drug and sexual behaviors in relation to HIV infection was investigated among 262 IVDUs in methadone clinics in New York City. Among female IVDUs, the HIV positive subjects reported larger numbers of sex partners than those subjects who were HIV negative, and those who had larger numbers of sex partners were more likely to be depressed. The IVDUs who had larger numbers of needle-sharing partners at shooting galleries were more likely to be HIV positive. Intervention programs should focus on IVDUs who are sexually active females, sharing needles at galleries, still using heroin and cocaine, and who began using heroin at an early age. PMID- 1938004 TI - Intergenerational differences in i.v. drug use behaviors: implications for HIV prevention. AB - The spread of the human immunodeficiency virus through the IV-drug-using population poses a serious public health threat. The tendency is to consider one IV drug user much the same as another. However, there are likely subtle differences in the behaviors of IV drug users depending on sexual, ethnic, and age differences. This study looks at the IV-drug-using behaviors of young adults 18 to 25 and adults over the age of 40. The drugs injected and rates of injection do differ for the two groups. This would suggest that HIV prevention should be tailored in response to the age differences of the targeted drug users. PMID- 1938006 TI - Whatever happened to marijuana? Patterns of marijuana use in Australia, 1985 1988. AB - Although marijuana remains the most widely used illicit drug in the world, the rise of cocaine has eclipsed it as the main focus of scholarly research. It remains unclear, outside of the United States, to what extent marijuana use has declined in the late 1980s, and whether the risk for particular age and sex groups has changed. In this paper, national population survey data collected in 1985 and 1988 are used to examine changing patterns of marijuana use in Australia, with particular reference to adolescents. The results show that while adult experience of marijuana has changed little, female adolescent experience increased significantly during the period, while male adolescent experience declined. There is a strong association between marijuana use and other drug use, notably illicit drug. Tobacco use remains an important association with marijuana among adolescents. PMID- 1938005 TI - Self-efficacy related to smoking cessation in general practice patients. AB - Many investigators have assessed smoking cessation rates following physician advice to quit. The reasons why some patients comply and others do not need to be examined. The present study assessed the relationship among three dimensions of self-perception and smoking cessation in a group of 199 patients of family practitioners. The cohort was followed for 6 months, and statistical models were developed based on measurements made immediately after advice and smoking status 6 months later. Analyses revealed that 70.0% of the group could be correctly classified as to their smoking status at follow-up and that some of the constructs of self-perception could be used to explain their behavior. Implications for treatment of smoking in family practice settings are discussed. PMID- 1938007 TI - Meperidine in detoxification of hospitalized heroin addicts. AB - Forty-six heroin abusers were hospitalized and treated with meperidine either alone or in association with clonidine. Meperidine was given orally in rapidly decreasing doses according to three different schedules. The majority of patients (87%) successfully completed the detoxification program. The best meperidine starting posology was 200 mg four times daily, which allowed stoppage of the opioid treatment after gradual reduction of the daily dose in a mean time of 9.5 days. Association with clonidine was not proven to be useful. This study shows that meperidine can be effectively used in rapidly decreasing doses in the pharmacological detoxification treatment of hospitalized heroin addicts. PMID- 1938008 TI - On the determinants of persistent gambling. III. Personality, prior mood, and poker machine play. AB - Sixty-four poker machine players were observed in the ecologically valid setting of their social club while completing a session of play. Subjects were assessed by interview, the Profile of Mood States, and personality measures. Personality scores did not predict level of involvement in gambling, session duration, or persistence when losing. High-frequency players were generally more predictable than other players, with over 70% of the variance of session duration accounted for by predictor variables. Also for this group of players, persistence when losing was significantly accounted for by prior mood and cognitions concerning win size. PMID- 1938009 TI - The Situational Confidence Questionnaire (Heroin). AB - This paper describes the derivation of a 22-item Situational Confidence Questionnaire for heroin users [SCQ (Heroin)]. Results revealed the SCQ (Heroin) to be an internally consistent scale with an acceptable level of test-retest reliability. Construct and discriminant validation were demonstrated through moderately significant correlations of all subscales with the short form of the Beck Depression Inventory. Factor analysis revealed a three-factor structure which could be labeled: coping with or enhancing arousal states, casual or occasional usage, and coping with negative emotions. PMID- 1938011 TI - Users and nonusers within a high risk milieu of cannabis use. A general population study. AB - A postal survey was carried out among a representative sample of nearly 2,000 young people in Norway (17-20 years old) in 1985, and followed up once again 2 years later. The sample was divided, according to the degree of exposure to cannabis in the peer milieu, into three groups: low, moderate, and high risk milieu. The differences between noncannabis users in high and in low risk milieux were the same as had been found in previous studies comparing users and nonusers of cannabis. The main differences between users and nonusers with a high risk milieu were that the users more often came from incomplete families and were men. All the differences between users and nonusers in the high risk milieu were small. This indicates that subsequent research should concentrate on the personality factors and social processes which encourage young people in the high risk milieu to resist the use of substances. PMID- 1938010 TI - AIDS education in drug user treatment programs. AB - This paper presents the results of an AIDS educational intervention for intravenous drug users (IVDUs) who participated in the New Jersey State Department of Health's Coupon program. An examination of the data showed that those with high pre-intervention test scores were more likely to have been White and to have been in treatment since 1981. Furthermore, the 1-hour AIDS educational intervention produced significantly higher post-intervention test scores (overall and for 27 of the 31 individual test items). Finally, none of the demographic and drug history variables used in this analysis were found to contribute significantly to the effectiveness of the educational session. PMID- 1938012 TI - Predicting length of stay in long-term treatment for chemically dependent females. AB - Psychological and demographic variables were analyzed for 136 chemically dependent women treated in a residential therapeutic community. Cocaine users constituted 50% of the sample and were likely to drop out of treatment earlier (p less than .05). Of all the variables studied, only the Beck Depression Inventory scores were significantly higher for clients who terminated treatment prematurely compared to clients who completed treatment. The results point to the need for further research on the role of depression as a predictive factor of retention. PMID- 1938013 TI - Thirty years of teaching psychotherapy skills. AB - The author outlines a basic model for teaching psychotherapeutic skills that includes five modules relating to (1) the dynamics of exploration, designed to encourage the patient's affective expression; (2) relationship structure, considering patterns of patient-therapist interaction along a closeness/separateness continuum; (3) affect, empathy, and distance regulation, emphasizing the crucial significance of identifying correctly and responding empathically to patients' affective messages; (4) basic cognitive interventions, focused on techniques for facilitating the patient's narrative flow and capacity to analyze experiences, and for formulating the patient's psychopathology; and (5) the therapist's use of self. The author concludes by examining why systematic psychotherapy training is particularly important at this time, in light of such pressures as managed health care, neuroscientific advances and psychopharmacologic breakthroughs, and the wave of self-help organizations. PMID- 1938014 TI - Use of the group in resolving the subjective countertransference. AB - Subjective countertransference can sharply limit any group leader's effectiveness. However, a therapist can use the group itself to identify such a bias and to remove it as an influence. A five-step method for doing this is presented. These steps begin with introspection but hinge upon the analyst's turning to the group for the vital information that, in the end, clarifies the analyst's own perceptions and helps him or her free the group from the harmful effects of any bias. PMID- 1938015 TI - Combining group psychotherapy and pharmacotherapy: a survey. AB - Group psychotherapists, primarily members of the American Group Psychotherapy Association, were surveyed to determine their practice and attitude toward inclusion of patients receiving psychotropic medication in their "typical" outpatient psychotherapy groups. One hundred forty-three questionnaire responses were received from 258 contacted practitioners (55.4% return rate). More than two thirds of the physicians, social workers, and psychologists reported including medicated members, and the professions did not significantly differ. Mood disordered patients were most frequently and schizophrenic and manic patients were least frequently reported to receive medication. Overall, clinicians' attitudes favored including medicated patients in the group. Indeed, therapists did not view inclusion of drugs as a detriment to the treatment process. Clinicians having only one medicated patient in their group felt more strongly that such individuals did not interfere with the treatment process when compared with those having none or more than one medicated patient. The one difference by discipline was that social workers and psychologists did not endorse the idea that medicated patients needed to be in groups led by psychiatrists. PMID- 1938016 TI - Antidepressants in group psychotherapy. AB - This article alerts us to consider depression as a relatively frequent cause of impasse in the course of group psychotherapy. The authors recommend the combined use of antidepressant medication along with group psychotherapy when such depression is confirmed independently outside the group. Common obstacles and pitfalls preventing successful combined treatment are reviewed; the depressive logjam is differentiated from common resistance; and profiles of responders versus nonresponders are described. A rationale of the combined treatment, its results, and implications for group therapists are all delineated. PMID- 1938017 TI - Complications in group psychotherapy with AIDS patients. AB - AIDS has a unique set of characteristics that makes group psychotherapy more complex than with other populations: (1) the threat of an early death, (2) a highly variable course of illness, and (3) stigma related to the illness and to the preexisting lifestyles of most patients. The specific ways in which the three factors seriously interfere with establishing and maintaining group cohesion are discussed, and clinical guidelines are suggested. In addition, a model for understanding and working with these and other issues in group psychotherapy, based on Erik Erikson's interpersonal theory of development, is presented. Finally, particular countertransferential difficulties are discussed in relation to the heightened emotionality common to AIDS psychotherapy groups. PMID- 1938018 TI - Level and form of psychopathology and the structure of group therapy. AB - Drawing upon concepts derived from ego psychological and object relations psychoanalytic theories of individual development and from a depth group psychology, the present empirical study, a naturalistic field investigation, explored hypothesized relationships between aspects of patients' psychological boundaries and structural features of inpatient therapy groups. More specifically, patients were assessed in terms of their level (i.e., psychotic vs. borderline organization) and form (i.e., anaclitic vs. introjective) of psychopathology. Their perceptions of themselves and of their therapy groups were measured following participation in two kinds of small group treatment designed to differ in terms of degree of internal structuring. Findings, generally supporting the hypotheses, showed the anaclitic borderline patients, in particular, to be most sensitive to structural variations and most adversely affected by an impersonal and highly structured treatment climate. Theoretical and practical implications of these findings were discussed. PMID- 1938019 TI - Self psychology and its relationship to the practice of group psychotherapy. AB - This article discusses self psychology as a theory of personality development and conceptual framework for diagnosing psychopathology. It seeks to show how specific components of this theory, including selfobjects, bipolar self, mirroring, tension arc, and nuclear self, can be compared with the "curative factors" of group psychotherapy, as presented by Yalom (1975). These include altruism, group cohesiveness, universality, interpersonal learning, guidance, and family reenactment. Existing literature is used to explain both theories and develop their synthesis. PMID- 1938020 TI - Treatment outcome of a group cognitive therapy program for depression. AB - A 12-session group program of cognitive therapy, designed by the first author, was evaluated with 35 persons suffering from major or minor depressive disorders. Effect-size scores were generated using the method of Nietzel, Russel, Hemmings, and Gretter (1987) and compared with cut-off points calculated using the method of Jacobson and Revenstorf (1988) and the norms established by Nietzel et al. (1987) in their meta-analysis. The effects of the Group Cognitive Therapy Program were found to be clinically significant according to the criteria of Jacobson and colleagues (Jacobson and Revenstorf, 1988; Jacobson, Follette and Revenstorf, 1984) for 73% of patients. It is concluded that the Group Cognitive Therapy Program is a clinically efficacious and cost-effective treatment for persons suffering from nonpsychotic, primary, unipolar depression. PMID- 1938022 TI - Effectiveness: a neglected dimension in the assessment of rehabilitation devices and equipment. AB - Effectiveness is a term used by research methodologists when referring to the attributes of a new health care intervention (e.g. device, medication, or procedure) which if lacking may result in its rejection despite its efficacy and efficiency. Administrators and consumers increasingly require evidence to ensure that a proposed new product or manoeuvre not only 'works' (efficacy, efficiency) but is 'practical' (effective). Yet, effectiveness data are rarely described in research literature or adequately measured. Common effectiveness qualities that might be considered in the formal evaluation of new rehabilitation devices and equipment are cost, convenience to the user ('user-friendliness'), and compliance with the local standards. This article identifies some of the most important variables related to these attributes and suggests strategies for appropriate data collection and analysis. A comparison of two products evaluated in an institutional setting is used to illustrate the suggested method. PMID- 1938021 TI - Oxygen-assisted exercise training in adult cystic fibrosis patients with pulmonary limitation to exercise. AB - Exercise training has been considered suitable only in cystic fibrosis (CF) patients with mild to moderate pulmonary dysfunction without progressive hypoxaemia during exercise. We trained 16 CF patients, all with advanced lung disease (mean standardized forced expiratory volume in 1 s (FEV1), 30% pred.), with a ventilatory limitation to exercise and a progressive hypoxaemia and hypercapnia at low maximal exercise capacity, Wmax (mean Wmax, 50% pred). Exercise training was performed on a cycle ergometer twice a day for 20 min at approximately 75% of the maximal predicted heart rate for at least 3 weeks. Supplemental oxygen was administered to reach a haemoglobin oxygen saturation of 90% during training. Patients considered malnourished because of a Quetelet Index of less than 20 kg m-2 received hyperalimentation orally or by duodenal tube (total 3500-4000 kcal day-1). Evaluation directly after the training period showed a statistically significant improvement in Wmax, maximal oxygen consumption, maximal minute ventilation, pulse, PaCO2 at rest, FEV1 and body weight. None of the pretraining variables was able to predict the outcome of the training programme in the individual patient. We detected no adverse effects of the programme. This study shows that oxygen-assisted exercise training in combination with correction of the nutritional status is safe and beneficial in CF patients with severe lung disease. PMID- 1938024 TI - Clinical findings as outcome predictors in rehabilitation of patients with sciatica. AB - In rehabilitation of patients with sciatica, factors prognostic of long-term outcome could prove beneficial in interventions and in evaluating progress toward fitness or capacity for work. In this study results of physical examinations, carried out one year after hospital treatment for suspected lumbar intervertebral disc herniation, were related to outcome after five-years, as assessed by the categorization of occupational handicap of the International Classification of Impairments, Disabilities and Handicaps (ICIDH). The sample consisted of 276 patients admitted to hospital in the years 1980-1982. Based on established clinical indications 179 patients underwent lumbar disc surgery and the remaining 97 received further conservative treatment. One year after hospitalization a physician and physiotherapist examined the patients at the Rehabilitation Research Centre (RRC) of the Social Insurance Institution in Finland. In 1986 the patients returned to the RRC for further evaluation of their occupational handicap at that time. Stepwise logistic regression analysis showed that sensory deficits of legs, tenderness in lumbar extension, decreased repetitive trunk flexion performance (sit-up test), decreased lumbar lordosis and tightness of hamstrings were indicative of a poor outcome in the operated group. For the non operated patients no statistically acceptable regression analysis model could be established. PMID- 1938023 TI - Token reinforcement in the psychosocial rehabilitation of individuals with chronic mental illness: is it effective over time? AB - The main purpose of this project was to determine whether the addition of the token economy reinforcement to the regular treatment modalities (medication therapy and psychotherapy) improved the following outcome measures: re hospitalization rate. NYPCC (agency) therapeutic goals, symptomatology, social integration activities and ADL skills. The research was carried out over a period of 18 months. Subjects were 617 individuals diagnosed as having chronic mental illness. They lived in three adult homes in New York, two of which were on a token economy programme, while the third served as a quasi-control group. The findings suggest that while medication therapy and psychotherapy have different effects in respect to the various outcome measures, the addition of the token economy programme resulted in positive, albeit marginal, gains to all outcome measures. PMID- 1938025 TI - The 'Open Road' project: real jobs for people with mental handicap. AB - This article describes the key elements of a three-year innovative project underway in Dublin, Ireland, which is applying the principles of supported employment. It covers the development of more integrated day services for adults with mental handicap, programme participants and activities, and key issues to be resolved in maintaining effective programmes of this kind. PMID- 1938026 TI - A community day care programme for psychiatric patients: the role of occupational therapy. AB - This paper examines the need for and role of occupational therapy in the organization and functioning of a community day care centre for psychiatric patients in a developing country. It highlights the debilitating effects of institutionalization associated with a previously established system of institutional care and explores the role of occupational therapy in facilitating the move away from that approach towards community-based day care centres for such patients. The paper describes the community care programme; the patients attending the programme; the methods used by occupational therapists to evaluate patients; and the effectiveness of the various individual, group and family focused methods of treatment deployed. PMID- 1938027 TI - Patients with neuro-muscular diseases: socio-psychological aspects. PMID- 1938028 TI - Evaluation of rehabilitation services in Nigeria. PMID- 1938029 TI - Evaluation of a comprehensive assessment battery for stroke patients. AB - The authors describe their experience of evaluating a battery of tests to assess function in patients with stroke and head injuries. They consisted of the Abbreviated Mental Test Score, Ravens Progressive Coloured Matrices, Hospital Anxiety and Depression Scale (HAD), Motricity Index, Shortened Rivermead Perceptual Assessment Battery (RPAB), Frenchay Aphasia Screening Test (FAST) and Barthel's Activities of Daily Living Index. These were applied to 50 patients, six of whom had had a head injury and 44 a stroke. Over 80% of subjects were able to complete the battery. Reasons for failure amongst the remainder were language problems, poor concentration and short term memory loss. Abnormalities in one aspect of cerebral function often compromised tests designed to assess another aspect of this. For example, upper limb incoordination interfered with RPAB, language difficulties affected the Abbreviated Mental Test, and HAD, and hemianopia compromised both RPAB and FAST tests. The battery can usually be completed within 1h, and could be performed by a wide range of professionals. It is likely to be particularly useful in screening for abnormalities requiring more detailed evaluation by particular professionals, and in monitoring the progress of patients during the course of treatment. PMID- 1938031 TI - Results of statutory rehabilitation measures in Germany. AB - The success of medical rehabilitation measures taken by the LVA Oberfranken and Mittelfranken in 1984 was scrutinized for 12,291 insured people. The criteria for evaluating success were the state of health of the insured persons before rehabilitation and at one month and one year afterwards. Two thirds of the insured persons were at work again one month after discharge from rehabilitation. One year after rehabilitation 14 per cent received a disablement pension. Only every second person insured who was ill before rehabilitation took up work again afterwards. Most of the insured people who were already receiving a pension before rehabilitation continued to receive their pension afterwards (86 per cent). The highest rate of inability to work and also the highest pension rate is found with insured persons suffering from an ischaemic cardiac disease. Only 33 per cent of these persons resume work after rehabilitation. PMID- 1938030 TI - Perceptions of mental handicap: a comparison of Australian and Irish school children. AB - Australian secondary school children (N = 955) were surveyed concerning their perceptions of persons with mental handicap. Data collected related to reactions to meeting a person with disability, helping the handicapped person, responses to specific statements about handicapping conditions, causes of disability and the need for further information about handicaps. Results showed some parallels between Australian and Irish school children with both groups reflecting the positive impact. PMID- 1938032 TI - Effects of anterior-tipped seating on respiratory function of normal children and children with cerebral palsy. AB - The purpose of this study was to compare the respiratory parameters of tidal volume, respiration rate, and minute ventilation of a group of six normal children and a group of six children with spastic cerebral palsy, in response to two seat base positions: (1) flat, and (2) anterior-tipped. Respiratory inductance plethysmography was used to record respiratory parameters. The results demonstrated significant differences in tidal volume and minute ventilation between the groups in the anterior-tipped seat condition. No significant differences in respiratory parameters could be attributed to seat base position within either the normal or cerebral palsied subjects. Implications are discussed in relation to the anterior seat base design, group data analysis methods and individual data profiles, and the impact of these results for future research and practice. PMID- 1938033 TI - Relocation and the characteristics of hospital and hostel regimes. AB - Drawing on evidence from a research evaluation of a local community care programme, this paper explores whether relocation from a British National Health Service mental handicap hospital into local authority hostels (supervised residential facilities) brought about a qualitative change in the residential environment of movers towards less restrictive management practices and caring routines, more responsive attitudes towards their rights and needs as individuals, and greater control over their own lives. The conclusions point to the existence of a substantial measure of overlap in the fundamental characteristics of the hospital and hostel regimes. PMID- 1938034 TI - Assessment chart for inpatient rehabilitation following stroke. AB - In order to enable comparison of the post-stroke patient's functional status between different points during the rehabilitation process, an assessment chart was developed; this covered cognitive, basic and integrated functions. The chart was applied by two independent examiners on 36 patients, with a mean age of 60, admitted consecutively for rehabilitation following stroke. The results of the assessment using the chart were compared with those measured with the Kenny Self Evaluation System. There was a positive correlation both between the Kenny System and the developed chart and the two examiners. It is felt that the chart meets the demands of easy applicability, numerical scoring and comprehensiveness. It is sufficiently sensitive to reflect the progress of patients during rehabilitation and enables re-evaluation of initial treatment plans focusing on the needs of the individual patient. The developed chart may serve as a useful tool in the evaluation of stroke inpatients during their rehabilitation. PMID- 1938035 TI - Blind infant-sighted mother interaction during the first year. PMID- 1938036 TI - Self-stimulation and occupational responding in low-functioning persons. PMID- 1938037 TI - Evaluation of lower leg orthosis use following cerebro-vascular accident. PMID- 1938038 TI - Investigating stigma within the stress process. PMID- 1938039 TI - Importance of four variables of walking to patients with stroke. PMID- 1938040 TI - Ultrasonic determination of bladder volume in patients with spinal cord injury. PMID- 1938041 TI - Immediate memory for haptically-examined braille symbols by blind and sighted adults: effects of item size. PMID- 1938042 TI - Survey of ten infants exposed prenatally to maternal cocaine use. PMID- 1938043 TI - Usefulness of a medicopsychological questionnaire for lung patients. PMID- 1938044 TI - Vulnerability of developing brain to undernutrition: claims of selective sensitivity of the cerebellum found to be misleading on theoretical and empirical grounds. AB - The growing rat brain acquires most of its weight, cells, and other material during the suckling period. Undernutrition at this stage can diminish brain growth. Nutritionally induced depressions of cerebellar growth may be smaller or larger than corresponding depressions in other brain regions, but when the resulting deficits are transformed to '% of age control values', the cerebellar deficits appear specially large. The ubiquitous '% transformation' and its misrepresentation of cerebellar deficits have nurtured the impression that cerebellum has a special sensitivity to insult. The sensitivities of cerebellum and forebrain growth in rats were compared empirically. Data came from a large set constructed, some years ago, from measurements made of regional DNA contents. The animals had been raised from birth to various ages in small (well-fed) or large (underfed) litters. Growth curves were fitted, from which rate curves were derived, and these showed the depression in rate of DNA accumulation to be the same for each region, throughout suckling. The widely held extra-sensitivity of cerebellum is explained as an artifact of the % transformation, the timing of cerebellar growth, and the timing of restriction which experimenters usually choose. Problems of inferring uniformity, or otherwise, of growth rate depressions from incomplete, noisy, and badly sampled growth data are discussed and illustrated with computer simulations. PMID- 1938045 TI - Expression of metallothionein-human growth hormone fusion genes in transgenic mice results in disproportionate skeletal gigantism. AB - Transgenic mice harbouring mouse metallothionein I-human growth hormone (MT-hGH) fusion genes were produced using the microinjection technique. The bones of adult MT-hGH transgenic mice, which continuously expressed high levels of hGH in their serum, and age-matched controls lacking detectable concentrations of hGH were measured microscopically. In addition to analyzing absolute skeletal dimensions, measurements were related to the cube root of the maximum body weight of the same animal. Absolute values obtained from transgenic mice were significantly higher than those obtained from controls for most of the defined measurements. However, the increase in skeletal dimensions was mostly not as pronounced as the increase in body weight and all bones were not affected to the same extent. There was no significant correlation between the serum GH concentration in individual mice and their degree of bony overgrowth. A disproportionate skeletal gigantism in MT-hGH transgenic mice may result from time differences in epiphyseal union of various bones of both sexes as well as differences in mechanical bone loading due to a drastically increased body weight. Individual concentrations of locally produced tissue insulin-like growth factor I (IGF I) might also play a role. Possible effects of these factors are discussed. The results presented in this study show that MT-hGH transgenic mice provide a powerful tool for the investigation of hormonal regulation of bone growth. PMID- 1938046 TI - Human stature: which growth model? AB - The performance of the 6-parameter model No. 3 of Preece and Baines (1978) for growth in human stature is compared with that of the 5-parameter model No. 1 and of the recent 7-parameter JPPS model (Jolicoeur et al., 1988) on data ranging from birth to adulthood about 27 healthy children from the French auxological survey. Model No. 3 has slightly larger residual mean squares on the average, in spite of its additional parameter, and is less robust than model No. 1. The JPPS model passes through the origin, fits infants as satisfactorily as older children and has much smaller residual mean squares than the models of Preece and Baines. The recently revised 6-parameter model of Kanefuji and Shohoji (1990) is not invariant with respect to time scale. JPPS appears to be the most satisfactory asymptotic model for growth in human stature at the present time. PMID- 1938047 TI - Specific heat output (SHO) of visceral organs/tissues: the hypothesis and first estimations. AB - It was hypothesized that each organ/tissue has a characteristic specific heat output (SHO; kcal/d.g). Heat output (HO; kcal/d) is defined as the product of the SHO and the weight, g, of the organ/tissue. FHP (fasting heat production) is defined as the sum of HO values of all tissues of fasted animals. FHP and organ weight were perturbed by variations of food intake of 48 young swine before FHP and weights of 36 organ/tissue variables were measured. Cluster analysis was used to group the variables and simplify the analyses and indicated that small intestine, kidneys, liver and pancreas were principal sources of FHP. Regression estimates indicated that the SHO of pancreas and kidneys was high (1.1 to 1.9), that of small intestine, liver and colon was intermediate (.21 to .26), and that of stomach and lungs was low (.11 to .14). All other viscera tissues were assumed to have SHO near that for nonviscera, estimated at .0165 kcal/d.g. Mean values of FHP and empty body weight were 1856 kcal/d and 46,651 g respectively; thus the mean SHO value of all tissues was about .04 kcal/d.g. The SHO values of stomach, intestine, colon, pancreas, kidneys, liver and lungs were in the range 3- to 50 fold greater than SHO of the whole body and in the range 7- to 120-fold greater than the estimated SHO of the nonviscera. These findings indicate that the small intestine, liver and kidneys account for about 60% of HO from viscera or about 30% of total FHP. PMID- 1938048 TI - Body weight and longevity in genetically obese and non-obese mice fed fat modified diets. AB - Polygenically obese and genetically related non-obese male mice were fed ad libitum purified diets differing in quantity or type of fat from weaning onward to determine effects upon weight gain and life span. Non-obese mice lived 71% longer than mice in the obese line (mean = 753 d versus 441 d). Obese mice fed a low-fat diet containing 1% corn oil by weight lived 26% longer than their obese counterparts fed high fat diets containing 20% additional fat as either corn oil or beef tallow. The low fat diet had more of a normalizing effect upon longevity than upon body weight in polygenically obese mice. Conversely, dietary fat concentration had little effect upon longevity in non-obese mice and more effect upon body weight than in genetically obese mice. Type of dietary fat had little effect upon body weight and no effect upon longevity. The results of this study suggest that life span was only partially explained by body weight, and furthermore, that genetics play a greater role than body weight or dietary fat concentration in determining life span. PMID- 1938049 TI - Cutaneous manifestations of acquired immunodeficiency syndrome in children. AB - Cutaneous disorders are among the most common manifestations of HIV infection in both children and adults. Because of the obvious visibility of the integument, these lesions are often the presenting manifestation of HIV-related disease. The cutaneous afflictions are frequently related to the sequelae of impaired immunity and include opportunistic infections and neoplasms as well as dramatic exacerbations and/or the development of rapidly progressive and severe manifestations in pre-existing, normally benign dermatoses. In many cases of AIDS, iatrogenic cutaneous disorders associated with toxic or allergic drug reactions are seen. With the increasing incidence of pediatric HIV infection and with therapeutic prolongation of survival, certain cutaneous manifestations (especially drug reactions) are likely to become more common. Kaposi sarcoma and other neoplasms may be recognized with increased frequency in HIV-infected children. New or previously unrecognized cutaneous manifestations of pediatric AIDS are likely to emerge. Familiarity with the various dermatologic presentations of pediatric AIDS can result in the earlier diagnosis and treatment of the disease and, hopefully, the prolongation of the patient's life. PMID- 1938050 TI - Keratinocyte grafts and skin equivalents. PMID- 1938051 TI - Invisible dermatoses. Additional findings. PMID- 1938052 TI - Use of dermatologic agents. How they differ worldwide. PMID- 1938053 TI - Diabetic foot infections. Pathophysiology, diagnosis, and treatment. PMID- 1938054 TI - Prognosis of atopic dermatitis. A prospective study in early adulthood. AB - The course and development of atopic symptoms were followed up in 801 atopic dermatitis patients, in 207 allergic rhinitis or asthma patients, and in 517 control subjects. The patients were studied in the Dermatology Clinic during their teens and the follow-up studies were carried out at the ages of 22-41. Persistent or frequently relapsing dermatitis occurred in 77-91% of those who suffered from severe or moderate atopic dermatitis during their teens and in more than one half of those patients who only had mild dermatitis at the corresponding age. Atopic dermatitis had started in 13-17% of allergic rhinitis/asthma patients. At the time of the follow-up examination, severe dermatitis was seen in only six percent and moderate symptoms in 35% of atopic dermatitis patients. Dermatitis was generally seen in multiple loci: on the face, hands, extremities, and body. Deterioration of dermatitis in autumn and winter was experienced by one third to 88% of the atopic dermatitis patients. Psychic stress was experienced as a major aggravating factor in one half to two thirds of atopic dermatitis patients. Prick test positivity occurred in 62-89% of the dermatitis patients. Animal allergens, molds, grasses, birch, and house dust mite were the most common allergens. Associations between evident allergen exposure and deterioration of the dermatitis occurred in individual cases. PMID- 1938055 TI - Lyme disease in Rio de Janeiro, Brazil. AB - Five patients living in Rio de Janeiro, Brazil, were found to have Lyme disease. These are among the first known cases in South America. PMID- 1938056 TI - Tinea capitis in adults in southern Taiwan. AB - We report the clinicomycologic study of 27 culture-proven cases of tinea capitis from southern Taiwan during the years 1988 to 1990. The series is notable for its predominance of adults (63%), of women (89%), and of Trichophyton violaceum infection (74%). The age distribution was clearly bimodal; the median age was 6 years for children and 56 years for adults (older than 18 years). Whether or not these findings represent a new trend of tinea capitis in southern Taiwan remains to be determined. Clinically, our cases of black-dot ringworm caused by T. violaceum often presented with subtle changes of scaling, hair loss, and black dots. The keys to the correct diagnosis are (1) a high clinical index of suspicion with careful inspection of the scalp for the presence of black dots, and (2) microscopic examination and culturing of the black dots or plucked hairs. PMID- 1938057 TI - Tear gas dermatitis. Allergic contact sensitization due to CS. PMID- 1938058 TI - Lepromatous leprosy mimicking porphyria cutanea tarda. PMID- 1938059 TI - Bibliography of secondary sources on the history of dermatology. III. Books, monographs, and chapters in English supplemented through 1990. PMID- 1938060 TI - Naftifine treatment of resistant dermatophytosis. AB - Despite an array of topical and systemic antifungal agents, cases of resistant dermatophytosis still exist. Use of naftifine, the first commercially available allylamine derivative, proved successful in the management of four such cases. PMID- 1938061 TI - The platina papule: from Plato to Paris. The London, Paris, and Vienna schools and their influence on the development of the dermatologic alphabet. PMID- 1938062 TI - Giardiasis, cryofibrinogenemia, and cold sensitivity: a response to metronidazole. PMID- 1938063 TI - Localization of cadherin cell-adhesion molecules in the skin lesion of darier disease. PMID- 1938064 TI - Unilateral areolar and periareolar tinea versicolor. PMID- 1938065 TI - The role of neutrophils in the pathogenesis of psoriasis. PMID- 1938066 TI - Keratinocytic versus neutrophilic causation in psoriasis. PMID- 1938067 TI - Possible cross-reactivity between hydrochlorothiazide and sulfanilic acid. PMID- 1938068 TI - Scalp mycetomas in Saudi Arabia. PMID- 1938069 TI - Lyme disease. PMID- 1938070 TI - Lymphoid proliferation and lymphoma associated with human retroviruses (HTLV and HIV). AB - There are rapidly increasing opportunities for dermatologists to see patients suffering from retrovirus infections. The HTLV-I was the first class of human oncogenic retrovirus that was found in cultured cells of a patient with skin manifestations similar or identical to those of CTCL (MF). It was soon recognized as the agent causing ATLL. The skin manifestations, histopathology, and immunophenotypes of ATLL share many similarities with MF and SS. Both HTLV-I and HIV-I (HTLV-III) cause immunodeficiency with an increased susceptibility to opportunistic infections. Persistent generalized lymphadenopathies are the initial manifestations of most of the HIV infections. The incidence of lymphoid malignancies is expected to become much higher as the life span of AIDS patients is prolonged. They can have both B-cell and T-cell non-Hodgkin lymphomas, although the incidence of the latter (B-cell lymphoma) is still much higher than that of the former. All human retroviruses are transmitted in similar ways. PMID- 1938071 TI - Disseminated histoplasmosis and human immunodeficiency virus infection. PMID- 1938072 TI - Skin irritation. In vitro assays. PMID- 1938073 TI - The molecular target for suppression of contact hypersensitivity by ultraviolet light. PMID- 1938074 TI - Surgical notes. Dermabrasion and hypertrophic scars. PMID- 1938075 TI - Primary localized amyloidosis in one family. AB - Primary localized amyloidosis was found in a family. A 66-year-old woman had suffered from hoarseness for 18 years. A biopsy specimen from the larynx showed amyloid deposits in the submucosal connective tissue. Her 40-year-old daughter noticed a subcutaneous nodule on her philtrum. Histologic examination showed the deposition of amyloid in the middle and lower dermis, which also encased the blood vessels and epidermal appendages. In both cases the amyloid deposits were positively stained with Congo red and the staining was resistant to potassium permanganate treatment. These amyloid deposits were strongly positive against the anti-amyloid antibody of the lambda light chain. These results indicate that the amyloid substance is derived from protein AL. There was no clinical or laboratory evidence of systemic amyloidosis or multiple myeloma in either patient. PMID- 1938076 TI - Annular erythema. A comparative study of Sjogren syndrome with subacute cutaneous lupus erythematosus. AB - Annular erythema developed in 22 patients with Sjogren syndrome. Clinically, the annular erythema was subdivided into three forms: Sweet disease-like annular erythema with an elevated border (14 cases); subacute cutaneous lupus erythematosus (SCLE)-like marginally scaled erythema (5 cases); and papular erythema (3 cases). Histopathologically, features commonly seen in annular erythema are deep perivascular and/or periappendageal infiltration of the lymphocytes with an admixture of neutrophils or plasma cells and less frequent epidermal changes suggestive of cutaneous lupus erythematosus. Immunoglobulin or complement deposition along the dermoepidermal junction of lesional skin was observed in 8 of 18 cases, and most of the dermal infiltrates consisted of CD4(+), 4B4(+) cells. The appearance of anti-SS-A(Ro) (100%) and anti-SS-B(La) (77%) was significantly higher in patients with annular erythema. These results suggest that patients with Sjogren syndrome might have a distinct annular erythematous lesion that is both clinically and histopathologically different from SCLE, although close immunologic abnormalities exist in these two diseases. PMID- 1938077 TI - Simultaneous occurrence of subacute cutaneous lupus erythematosus and Sweet syndrome. A marker of Sjogren syndrome? AB - A 78-year-old man presented simultaneously with subacute cutaneous lupus erythematosus (SCLE) and Sweet syndrome (neutrophilic dermatosis). He was subsequently investigated for and found to have Sjogren syndrome. We believe that the simultaneous occurrence of the above cutaneous manifestations are very suggestive of and should prompt investigation for Sjogren syndrome. PMID- 1938078 TI - Sweet syndrome associated with acute myelogenous leukemia. Atypical form simulating facial erysipelas. AB - A case of Sweet syndrome in a patient with an acute myelomonocytic leukemia is reported. It is an unusual case simulating a facial erysipela. This case illustrates the difficulty in differentiating infection from Sweet syndrome in an immunocompromised patient. The negative cultures, ineffective antibiotics, and histopathologic examination results allowed the onset of corticosteroid therapy. The phagocytic function of the neutrophils studied by chemoluminescence was normal in the patient. The physiopathology of Sweet syndrome is discussed, in particular the role of cytokines in the accumulation of granulocytes. PMID- 1938079 TI - Sweet syndrome in chronic myelogenous leukemia. PMID- 1938080 TI - Congenital preauricular sinuses associated with dark hair coloration in one family. PMID- 1938081 TI - Segmental lichen aureus in a child. PMID- 1938082 TI - Mammary gland involvement in mycosis fungoides. PMID- 1938083 TI - Reticulate pigmentation in mycosis fungoides. PMID- 1938084 TI - Topical metronidazole gel. The bacteriology of decubitus ulcers. AB - Ten putrid-smelling decubitus ulcers were successfully treated with metronidazole gel. Anaerobes were cultured from five ulcers and Wood's light examination was positive in four ulcers before treatment. The odor was eliminated after 36 hours of therapy. All results of post-treatment cultures of anaerobes and Wood's light examinations were negative. PMID- 1938085 TI - Naftifine treatment of trichomycosis pubis. AB - Naftifine hydrochloride 1% cream is a recently developed material of proven efficacy in superficial cutaneous fungal infections. The drug has also been reported to have significant antibacterial properties as well. A case of trichomycosis pubis, a bacterial disorder that can easily be mistaken for several fungal diseases, responded to application of naftifine cream. The authors suggest that this medication may be the drug of choice when the clinical presentation consists of nodules encircling pubic or axillary hair. PMID- 1938087 TI - Delayed pressure urticaria and egg allergy. PMID- 1938086 TI - Classification of skin diseases by Noah Worcester. PMID- 1938088 TI - Pseudoporphyria due to cola. PMID- 1938089 TI - Practicing dermatology in a Gulf country. PMID- 1938090 TI - Leprosy and psoriasis occurring together. PMID- 1938091 TI - Malignant syphilis or syphilis simulating malignancy. PMID- 1938092 TI - Secular trend in body mass index in the adult population of three communities from the upper mid-western part of the USA: the Minnesota Heart Health Program. AB - Secular trend in body mass index (BMI) over 7 years (1980-1987) was examined in the upper mid-western part of the USA using annual cross-sectional data collected by the Minnesota Heart Health Program. Significant secular increase in BMI adjusted for age and education was found in both men (0.08 kg/m2/year, P less than 0.02) and women (0.19 kg/m2/year, P less than 0.0001). In women, the secular increase occurred throughout the distribution of body weights but the change in the upper end was two to three times greater than that in the other parts of the distribution. In men, most of the increase in BMI occurred in the upper end of the distribution. Prevalence of obesity (defined as BMI greater than or equal to 85th percentile at year 1: men, 30.16 kg/m2; women, 29.94 kg/m2) increased by 0.6 percent/year (P = 0.1) in men and by 1.0 percent/year (P = 0.002) in women. The results indicate that body weight is increasing in upper mid-western adults, probably largely as a result of already overweight individuals becoming more obese. The secular increase in BMI was not accompanied by systemic change in reported food intake and exercise, and could not be explained by decreased prevalence of smoking. Large increases in body weight, especially among those who are already overweight, may have a significant public health impact. PMID- 1938093 TI - Regulation of glucose homeostasis in pre-obese Zucker rats before and after weaning. AB - This study was undertaken to determine the changes which could occur in glucose homeostatis during the suckling-weaning transition in the genetically obese Zucker (fa/fa) rat. Glucose kinetics and glucose utilization in individual tissues were determined in 15-day-old suckling and 30-day-old weaned obese Zucker rats either in the post-absorptive state or during a glucose infusion. During suckling, glucose turnover rates in the basal state as well as glucose production and utilization during the glucose infusion were identical in lean and obese rats. Furthermore, individual tissue glucose utilizations were similar in the two groups of rats, except in brown adipose tissue where utilization was lower in obese than in lean rats during the glucose challenge. After weaning, glucose turnover rates and glucose utilization in individual tissues were identical in the two genotypes in the basal state. During the glucose infusion, hepatic glucose production was less suppressed in the obese. Furthermore, glucose utilization was significantly lower in muscles (extensor digitorum longus, tibialis anterior, diaphragm) and higher in white adipose tissue of obese rats. These data show that, before weaning, pre-obese Zucker rats present a perturbation only in the uptake of glucose in brown adipose tissue. Major defects in the regulation of glucose homeostatis occur after weaning. PMID- 1938094 TI - Trends in obesity in young adults in The Netherlands from 1974 to 1986. AB - Data from two screening projects on cardiovascular risk factors were used to investigate trends in body mass index (BMI; weight(kg)/height(m)2) and in the prevalence of obesity in The Netherlands between 1974 and 1986. In the period 1974-80 about 30,000 men and women aged 37-43, with a mean age of 40, were screened. In the period 1981-6 about 80,000 men aged 33-37, with a mean age of 35, were examined. In men, an increase in mean BMI of about 0.5 kg/m2 was observed between 1974 and 1980, which was reflected in an increase in the prevalence of a BMI between 27 and 30 kg/m2 of about 4 percentage points. In the period 1981-6, no change in mean BMI was observed in men, although there was a slight decrease in the percentage of men with a BMI between 25 and 27 kg/m2 (about 2 percentage points). In women, no change in mean BMI or in the prevalence of different grades of obesity was observed in the period 1974-80. The prevalence of grade I obesity (BMI 25-29.9 kg/m2) was 40-45 per cent in men aged 40 and 25 30 per cent in women aged 40 in the period 1974-1980. The prevalence of grade II obesity (BMI greater than or equal to 30 kg/m2) during that period was 5-6 per cent in men and 7-8 per cent in women. The prevalence of grade I and grade II obesity in men aged 35 was 35-40 per cent and 5-6 per cent respectively during the period 1981-6. The prevalence of grade II obesity in The Netherlands is comparable with that in some other Western European countries, but much lower than in the United States and Canada. PMID- 1938095 TI - Effect of obesity on plasma insulin-like growth factor-I in cancer patients. AB - Starvation and malnutrition are associated with low concentrations of plasma insulin-like growth factor I (IGF-I). To evaluate the utility of IGF-I as a screening test for malnutrition, we compared plasma IGF-I concentrations with anthropometric measurements of nutritional status in 99 cancer patients. Forty three percent of patients were overweight and 4 percent were underweight. Log IGF I correlated negatively with body weight (r = -0.31, P = 0.002), midarm muscle area (MAMA) (r = -0.31, P = 0.001), triceps skinfold thickness (TSF) (r = -0.24, P = 0.03) and body mass index (r = -0.31, P = 0.003). In males plasma IGF-I correlated with TSF but not MAMA; in females IGF-I correlated with MAMA but not TSF, suggestive of a sexual dimorphism between plasma IGF-I and indices of adiposity. We conclude that obesity was far more prevalent than undernutrition, and that plasma IGF-I correlated negatively with indices of adiposity in a gender specific fashion. Because IGF-I is significantly reduced in the obese as well as in the malnourished, measurements of plasma IGF-I are unlikely to be of adequate clinical specificity to serve as a useful screening test for subtle alterations in nutritional status. PMID- 1938096 TI - Determinants of weight loss after vertical banded gastroplasty. AB - Weight loss after gastric partition is highly variable even when the operation itself has been successful. We studied changes in body composition in relation to energy expenditure before and one year after surgery in one woman and five men, age 20-38 years, and BMI 42-62 kg/m2. Observations were performed shortly before, and 6, 12, 27 and 54 weeks after surgery. Body composition was measured with hydrostatic weighing and isotope dilution, and energy expenditure over 24 h (24EE) and during complete rest (sleeping metabolic rate (SMR)) with a respiration chamber and in five of the six subjects under daily living conditions over two-week intervals with doubly labeled water (average daily metabolic rate (ADMR). Weight loss and fat loss over the full observation period until 54 weeks after surgery was 54 +/- 8 and 43 +/- 9 kg (mean +/- s.e.m.), respectively. There was a more than three-fold difference in fat loss between the subject losing most, i.e. 70 kg, and the subject losing least, i.e. 20 kg. Fat loss was not related to initial fat mass in this group of six subjects but there was a significant negative relation with the loss of protein mass. There was a strong negative relation between fat loss and activity level of the subjects expressed as the quotient ADMR/SMR. These results show the contrary from what would be expected. Reduction of fat mass after successful gastric partition is highest in those subjects having the lowest physical activity level (before and) after surgery; these subjects lose less fat-free mass. PMID- 1938097 TI - Body fat in the adult Danish population aged 35-65 years: an epidemiological study. AB - The purpose of the study was: (1) to estimate body fat and body fat distribution in the general population of Danes aged 35-65 years and thus provide tables of normal values for adult Danes in these age groups; and (2) to assess the effects of age and gender on relations between measures of obesity and of fat distribution. Hitherto, the only available results from the Danish population have been on BMI. Of the 3608 invited subjects 2987 (83 per cent) attended the examination. Body fat and fat distribution were estimated from measurements of electrical impedance and from circumference measurements. The study showed large differences in body fat and fat distribution between men and women. There was a difference in total body fat of 4.5 and 6.9 kg in men and women respectively between the groups aged 35 and 65 years. Fat percentage increased 36 per cent in women and 30 per cent in men between the groups aged 35 and 65 years. There was a difference in waist/hip ratio (WH ratio) between men and women at all age groups. Of the women 46 per cent had WH ratios above 0.8 and 14 per cent of the men had WH ratios above 1.0, suggesting that cut-off points for WH ratio as an indicator of cardiovascular risk are population specific. This may be caused by a different distribution of other cardiovascular risk factors in the Danish population than in other populations. Men had larger WH ratios per body fat mass with age, whereas in women there was no effect of age on this relation. Furthermore the WH ratio increments in this population took place before the age of 55 years in men, but after 55 years in women. The results may contribute to explain gender differences in morbidity and mortality with increasing age. PMID- 1938098 TI - Central glucocorticoid regulation of parasympathetic drive to pancreatic B-cells in the obese fa/fa rat. AB - The effects of glucocorticoids on the insulin secretory response to an intravenous glucose load have been studied in lean (Fa/?) and obese fa/fa Zucker rats. The role of parasympathetic drive to the pancreatic B-cells was assessed as that component of the insulin secretory response that was blocked by pretreatment of the rats with intravenous atropine. The insulin secretory response to the glucose load was greater in obese than in lean rats. Atropine significantly reduced basal and stimulated levels of insulin in obese but not in lean rats. Adrenalectomy reduced basal insulin levels and the secretory response in obese but not lean rats and also abolished the atropine-blockable component of the response. Peripheral corticosterone replacement of adrenalectomized fa/fa rats restored the hyperinsulinemia. Chronic infusion of dexamethasone intracerebroventricularly to adrenalectomized fa/fa rats increased basal insulin and the secretory response to glucose and this effect was blocked by atropine. In contrast, intracerebroventricular infusion of obese rats with corticotropin releasing factor reduced basal and stimulated insulin levels. It is concluded that the hypersecretion of insulin in obese fa/fa rats results, at least in part, from a central glucocorticoid-mediated stimulation of vagal drive to the pancreatic B-cells. PMID- 1938099 TI - Quality of life after gastric bypass for morbid obesity. AB - One year after gastric restriction surgery, 70 per cent of 118 women completed a questionnaire about lifestyle and eating behaviour changes. Mean weight loss was 35.4 kg. Patients reported a moderate reduction in appetite, and most avoided specific foods which they previously enjoyed, usually because of epigastric discomfort and/or nausea and vomiting. Patients had initiated or resumed a mean of 1.8 activities, most of which involved physical exercise. Sexual interest, enjoyment and frequency were all increased. Raised sexual satisfaction correlated strongly with overall outcome satisfaction. Seventy-two per cent of respondents rated themselves as very pleased, and 18 per cent as fairly pleased, with the overall results of the operation, and responses to the open-ended questions were often strikingly enthusiastic. However, most patients emphasized the difficulty of adjusting to radically new eating habits in the first 2-3 months after surgery, during which they experienced their greatest need for social support and encouragement. PMID- 1938100 TI - Importance of the N-terminal domain of the type I angiotension II antagonist [Sar1,Ile8]ANG II for receptor blockade. AB - Analogues of the Type I angiotensin (ANG) antagonist, [Sar1,Ile8]ANG II, in which the N-terminal dipeptide was modified were synthesized by the solid phase method and purified by reversed-phase HPLC. Antagonist potencies (pA2) of the peptides were determined on the rat isolated uterus using ANG II as the agonist. Substitution of the Arg residue occupying position 2 of [Sar1,Ile8]ANG II (pA2 8.1) by Gly, Ala, Nle, Phe, Pro or Sar reduced the antagonist potency to pA2 = 7.0, 6.8, 6.7, 6.8, 5.8 and 5.3, respectively. Deletion of the N-terminal Sar residue in these same peptides gave pA2 = 6.8, 5.7, 5.5, 5.9, 6.1 and 7.5, respectively. The characteristically long duration of action of [Sar1,Ile8] was absent for all of these analogues including (des1, Sar2, Ile8]ANG II. These findings demonstrate that the antagonist potencies of Type I angiotensin antagonists for smooth muscle receptors, and also the long duration of action, are dependent on the location of positive charges within the peptide and on the conformation of the molecule in determining favorable electrostatic interactions with the receptor. A model is proposed in which the two positively charged loci on the angiotensin molecule (N-terminus and Arg) interact with two corresponding anionic binding sites on the smooth muscle receptor. The possibility that the prolonged duration of action of [Sar1, Ile8]ANG II results from binding to a different site on the angiotensin receptor from that occupied by ANG II is discussed in relation to the present findings. PMID- 1938101 TI - Isolation of a ribosome-inactivating and abortifacient protein from seeds of Luffa acutangula. AB - A glycoprotein with a molecular weight of 28,000 as estimated by SDS polyacrylamide gel electrophoresis was isolated from seeds of Luffa acutangula using a procedure that involved acetone precipitation, ion exchange chromatography on CM Sepharose CL-6B and gel filtration on Sephadex G-50. In immunodiffusion studies it was found to be immunologically distinct from abortifacient proteins isolated from other members of the Cucurbitaceae family including Momordica charantia, Momordica cochinchinensis, Trichosanthes kirilowii and Trichosanthes cucumeroides. There were some differences in amino acid composition among the proteins although there was a gross similarity. The protein from L. acutangula was capable of inducing mid-term abortion in mice and inhibiting protein synthesis in a cell-free system. PMID- 1938102 TI - Structure and conformation of a novel inhibitor of angiotensin I converting enzyme--a tripeptide containing phosphonic acid. AB - A novel phosphotripeptide, (IR)-1-(N-(N-acetyl-L-isoleucyl)-L-tyrosyl)amino-2-(4 hydroxyphenyl)ethy l- phosphonic acid, is a potent inhibitor of angiotensin I converting enzyme (ACE). ACE inhibitory activity in vitro of the peptide is comparable to that of captopril. Its diethylester (C29H42N3O8P, molecular weight, 591.6) crystallizes in the monoclinic space group C2, with cell constants: a = 25.666(9), b = 9.590(8), c = 13.557(2)A, beta = 91.65(2) degrees, Z = 4, Dc = 1.17 g/cm3. The structure was solved by MULTAN 11/82 and refined by full matrix least-squares methods to a final R-factor of 0.063 for 2123 unique reflections (F greater than 3 sigma(F] measured on an Enraf-Nonius CAD-4 diffractometer (CuK alpha, lambda = 1.541 8 A, T = 295 K). The absolute configuration of the alpha carbon where the phosphonic acid is attached was determined unequivocally by referring to the L-isoleucyl moiety whose absolute configuration is known. The conformation of the molecule is relatively rigid owing to the intramolecular requisites and the resultant relative disposition of hetero atoms, which are necessary to its biological activities, are confined to the corresponding disposition in captopril. PMID- 1938103 TI - Sulfonation of arginine residues as side reaction in Fmoc-peptide synthesis. AB - Several arginine-rich peptides containing the C-terminus of neuropeptide Y (NPY) were prepared by solid phase peptide synthesis using Fmoc chemistry and cleaved from the resin with trifluoroacetic acid (TFA). The products were characterized by fast atom bombardment-MS, LC-thermospray-MS, ion spray-MS/MS, and Edman degradation. The side products could be identified as peptides with sulfonated arginine residues resulting from an unexpected cleavage of Mtr or Pmc protecting groups. The degree of sulfonation depended on the choice and composition of the cleavage solution. Several scavenger mixtures were used and a mixture of thioanisole/thiocresol was found to be the most efficient for suppressing sulfonation. Furthermore treatment with the enzyme arylsulfate-sulfohydrolase desulfonated the peptides yielding the correct sequence. PMID- 1938104 TI - A synthetic peptide corresponding to a sequence in the GTPase activating protein inhibits p21ras stimulation and promotes guanine nucleotide exchange. AB - Amino acid sequence homology between the GTPase Activating Protein (GAP) and the GTP-binding regulatory protein, Gs alpha, suggests that a specific region of GAP primary structure (residues 891-898) may be involved in its stimulation of p21ras GTP hydrolytic activity (McCormick, F. [1989] Nature 340, 678-679). A peptide, designated p891, corresponding to GAP residues 891-906 (M891RTRVVSGFVFLRLIC906) was synthesized and tested for its ability to inhibit GAP-stimulated p21ras GTPase activity. At a concentration of 25 microM, p891 inhibited GAP activity approximately 50%. Unexpectedly, p891 also stimulated GTP binding to p21N-ras independent of GAP. This stimulation correlated with an enhancement of p21N ras.GDP dissociation; an approximate 15-fold increase in the presence of 10 microM p891. In contrast, dissociation of the p21N-ras.GTP gamma S complex was unaffected by 10 microM p891. The p21N-ras.GDP complex was unresponsive to 100 microM mastoparan, a peptide toxin shown previously to accelerate GDP dissociation from the guanine nucleotide regulatory proteins, Gi and Go. p21H ras, as well as the two p21H-ras effector mutants, Ala-38, and Ala-35, Leu-36, also exhibited increased rates of GDP dissociation in the presence of p891. Also tested were three ras-related GTP-binding proteins; rap, G25K and rac. The rap. GDP complex was unaffected by 10 microM p891. Dissociation of the G25K- and rac.GDP complexes were enhanced slightly; approximately 1.3- and 1.8-fold over control, respectively. Thus, the inhibitory effect of p891 on GAP stimulation of p21ras suggests that amino acids within the region 891-906 of GAP may be essential for interaction with p21ras. In addition, p891 independently affects the nucleotide exchange properties of p21ras. PMID- 1938107 TI - Conformation and hydration of aspartame. AB - Conformational free energy calculations using an empirical potential (ECEPP/2) and the hydration shell model were carried out on the neutral, acidic, zwitterionic, and basic forms of aspartame in the hydrated state. The results indicate that as the molecule becomes more charged, the number of low energy conformations becomes smaller and the molecule becomes less flexible. The calculated free energies of hydration of charged aspartames show that hydration has a significant effect on the conformation in solution. Only two feasible conformations were found for the zwitterionic form, and these are consistent with the conformations deduced from NMR and X-ray diffraction experiments. The calculated free energy difference between these two conformations was 1.25 kcal/mol. The less favored of the two solvated conformations can be expected to be stabilized by hydrophobic interaction of the phenyl groups in the crystal. PMID- 1938106 TI - A new detector for fully automatic peptide synthesis. AB - A new method of monitoring the rate of reactions in solid phase peptide synthesis is described. A conductivity detector in the reaction cell enables the deprotection, washing, and subsequent coupling stages to be examined in detail. The half lives of the reactions can be calculated and hence the optimum reaction times predicted. The aggregation of peptide chains and subsequent collapse of the resin is observed. Difficult sequences are sensed and appropriate action taken completely automatically. PMID- 1938108 TI - NMR studies on the conformation of cyclodipeptides with two identical L-aromatic amino acid residues in solutions--cyclo[L-5(OH)Trp-L-5(OH)Trp] and cyclo[-L-Phe-L Phe]. AB - NMR studies on the conformations of cyclodipeptides containing two identical L aromatic amino acid residues cyclo[-L-5(OH)Trp-L-5(OH)Trp]8 and cyclo[-L-Phe-L Phe]9 in DMSO solutions are reported here. The 1H chemical shifts, the spin-spin coupling constants, and the NOE results show that in these two cyclodipeptides one residue occupies the folded antiperpendicular and the second the extended to nitrogen perpendicular conformers respectively. The results indicate that each of the identical residues is in a fast conformational equilibrium between the above two conformers so that one set of 1H and 13C resonances is observed for the two identical residues in the above two cyclodipeptides. PMID- 1938105 TI - Immunosuppressive analogues of hexapeptide Tyr-Val-Pro-Leu-Phe-Pro, an immune system stimulant. AB - It was found that substitution of Val2 and/or Leu4 residue in a hexapeptide Tyr Val-Pro-Leu-Phe-Pro (I) transforms this peptide immunostimulant into analogues possessing the immunosuppressor activity--Tyr-Gly-Pro-Leu-Phe-Pro (II), Tyr-Val Pro-Gly-Phe-Pro (III), and Tyr-Gly-Pro-Gly-Phe-Pro (IV). Biological effects of peptides I-IV were studied using PFC (plaque forming cell) test, GvH (graft vs host) reaction in mice, and ARFC (autologous rosette forming cell) test. The strongest immunosuppressor activity was observed for III--in this case the immunosuppressor effect was observed even in PFC test in vitro in which II and IV showed no such activity. These results suggest that simultaneous presence of both Val2 and Leu4 residues is necessary for the generation of immunostimulation. The CD study of I-IV in methanol solution suggests that the conformational preferences of II-IV change towards stabilization of the beta-turn structure, whereas in the case of I the gamma-turn on Leu4 and cis' orientation of the Pro3 carbonyl (distorted beta-turn of type I) was found as the preferred conformation. Competition in biological effects observed for I and III in PFC in vitro test suggests that these analogues may interact with the same cellular receptor. Drastic changes in the activity which accompany changes in the sequence are discussed in the terms of our stereochemical hypothesis. PMID- 1938109 TI - Conformational analysis and aqueous hydration studies of model peptides for the adhesive protein of the mussel, Mytilus edulis L. AB - Conformations of model peptides of the adhesive protein of the mussel, Mytilus edulis L were investigated using molecular mechanics. The protein structure was represented as the repeat of a 10-residue unit. This decamer, and di- and tri decamers of it, were considered in the modeling. Incorporation of the unusual dopamine residue in the decamer repeat may be explained by its hydrogen bond forming ability via its 3-OH group to a proline carbonyl oxygen. This bond contributes to maintaining a double reverse beta-turn structure in the decamer. This conformation was found more stable than 3(1) and alpha helical conformations. Adjacent reverse beta-turn structures are connected by short segments (2 to 3 residues) having little conformational preference. Thus, the overall protein can possess a significant random nature, yet have a highly ordered embedded conformational component. Hydrophilic character is in line with the larger number of OH groups on the phenyl ring for residue 9 (the site of the Dopa residue). The dehydration free energy of the (3-OH)-Phe as compared to the Dopa derivative is less by 1.4 kcal per decamer unit. This amounts to more than 100 kcal energy gain in the dehydration process for the total protein. PMID- 1938111 TI - Fifteen clinical accounts of psychoanalysis. PMID- 1938110 TI - Purification and primary structure of glucagon from ostrich pancreas splenic lobes. AB - Glucagon is a highly conserved polypeptide hormone which appears to play a more important role in regulation of glycaemia in birds than insulin. Ostrich glucagon was isolated and purified from ostrich pancreas splenic lobes using an adapted acid ethanol extraction procedure, gel filtration, ion exchanges, and HPLC steps. The purified glucagon fraction appeared to contain small quantities of a more acidic contaminant (polyacrylamide gel isoelectric focussing, PAGE) but appeared homogeneous on SDS-PAGE. Amino acid analysis and sequence analysis showed identity with the duck hormone. Identity with the duck hormone was confirmed by liquid phase as well as gas phase sequencing. The ostrich glucagon preparation seemed to have a higher Km than the porcine homologue in stimulating glycerol release from isolated chicken adipocytes. PMID- 1938112 TI - Clinical case description of a segment of a psychoanalytic experience. PMID- 1938113 TI - Comments on the treatment of a narcissistic patient. PMID- 1938114 TI - Therapy with a sexually abused woman. PMID- 1938115 TI - From raging bull to Theseus; the long path of a transformation. PMID- 1938116 TI - The psychoanalytic treatment of two maternally over-protected young men. PMID- 1938117 TI - Clinical approach to a narcissistic aspect. PMID- 1938118 TI - Evolution of the transference in a case of homosexuality declined. PMID- 1938119 TI - Relationship between extratransference interpretations and transference interpretations: a clinical study. PMID- 1938120 TI - Analytical dialogue and psychic change. A clinical perspective. PMID- 1938121 TI - The case of a young university student. PMID- 1938122 TI - The body as a stage for criminal acting out. PMID- 1938123 TI - A river can't be green, can it? From the analysis of Boris. PMID- 1938124 TI - Fragment of the analysis of an hysterical patient. PMID- 1938125 TI - The consequences of an instance of acting out in the countertransference. PMID- 1938126 TI - The relationship between serum testosterone level and Hoffmann reflex from the long flexor thumb muscle in right-handed young adults. AB - The relationship between serum testosterone level and Hoffmann (H) reflex from right to left thumb flexors was studied in right-handed young men and women. The subjects were divided into two subgroups: fast and slow in right-hand skill, but no difference in left-hand skill (peg moving). The mean serum testosterone level was found to be significantly lower in subjects with fast right hand than those with slow right hand. The mean H reflex from right was significantly smaller in subjects with fast right hand than those with slow right hand. There was a negative, linear relationship between serum testosterone level and amplitude of H reflex from right thumb. This was more pronounced in females than males. The H reflex from left was not significantly associated with serum testosterone levels. It was concluded that testosterone may affect the somatomotor system of the left brain during adolescence impairing the right-hand skill especially in females. These results also appear to be in accord with the testosterone theory of cerebral lateralization. PMID- 1938127 TI - The relationship of tardive dyskinesia to positive schizophrenia. AB - Investigations aimed at identifying the clinical characteristics that discriminate Tardive dyskinesia (TD) from non-TD patients have yielded disparate findings. A number of studies have suggested that TD may be a feature of negative schizophrenia. In particular, the association of TD with high prevalence of "soft" neurological signs, cognitive deficits, and abnormal brain morphology on CT scan in some patients, have led several investigators to propose that negative schizophrenia may be a risk factor for TD. The neurochemical profile of TD, however, is not consistent with this hypothesis. In the following communication, we present our studies which suggest that TD is specific to and an intergral part of positive schizophrenia. The data suggest that schizophrenic patients with predominant positive symptoms may be at increased risk for the development of TD. In addition, we present evidence linking TD with left cerebral hemispheric dysfunction. By comparison, we provide evidence that negative schizophrenia is related to diencephalic damage, and discuss its relevance to negative schizophrenia and to Parkinsonism. We also provide evidence that negative schizophrenia may be a risk factor for acute drug-induced dystonia. Thus, these findings are consistent with our model that negative schizophrenia is a risk factor for Parkinsonism, whereas positive schizophrenia is related to TD. In analogy with the positive/negative dichotomy of schizophrenia, we propose that TD could be considered a "positive," where Parkinsonism a "negative" movement disorder. PMID- 1938128 TI - The relationship between serum testosterone and visuomotor learning in hand skill in right-handed young women. AB - The relationship between serum testosterone level and motor learning in hand skill was studied in right-handed young women. Hand skill was assessed by a peg moving task. Subjects were required to shift 25 pegs from one of two parallel rows to the corresponding holes as fast as possible, first with right and then with left hand. One trial consisted of the time elapsed to move 25 pegs with one hand. Ten trials were performed by each hand. Peg moving times for the right and left hands linearly decreased at each successive trial (visuomotor learning). Subjects were divided into two subgroups as those having serum testosterone concentrations below and above the mean. The right hand skill and its motor learning was found to be better in subjects with low testosterone than those with high testosterone. The left hand skill was better in subjects with low testosterone than those with high testosterone; there was no significant difference in the left-hand learning in subjects with low and high testosterone (parallel regression lines). Motor learning linearly decreased with testosterone for the right hand, not for the left hand. These results seem to be in accord with the testosterone theory of cerebral lateralization (Geschwind & Behan, 1982). PMID- 1938129 TI - Antinociceptive properties of inhibitors of endopeptidase 24.15. AB - Endopeptidase 24.15, a metalloendopeptidase active in brain, rapidly converts prodynorphin-derived peptides into leu-enkephalin. Inhibitors of this enzyme slow the degradation of these peptides in vivo and in vitro. The present study evaluated two inhibitors of endopeptidase 24.15, N-[1-(RS)-carboxy-3-phenyl propyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB), and N-[1-(RS)-carboxy-3 phenylpropyl]-Ala-D-Ala-Phe-p-aminobenzoate (cFP-A(D)AF-pAB), for antinociception on the tail-flick and jump tests in rats following intracerebroventricular administration relative to an inhibitor of endopeptidase 24.11, N-(1-(RS)-carboxy 3-phenylpropyl]-Phe-p-aminobenzoate (cFP-F-pAB). cFP-AAF-pAB, cFP-A(D)AF-pAB and cFP-F-pAB produced equipotent dose-dependent (25-250 nmol) and time-dependent (5 7 h) antinociception with larger effects on the jump (49-51% increase) relative to the tail-flick (28-41% increase) test. Naloxone (1 mg/kg, SC) significantly reduced antinociception elicited by all inhibitors on the jump test. Motor performance failed to be affected by inhibitor administration. The gradual appearance of antinociception and its naloxone sensitivity suggest that these effects are mediated through inhibition of opioid peptide degradation. PMID- 1938130 TI - Activation-induced changes in evoked and slow brain potentials: effects of cocaine in awake rabbit. AB - To study the interrelations between event-related potentials and brain activation, evoked responses to visual stimulation registered from occipital cortex and hippocampal CA1 region were investigated in awake animals administered cocaine (2 mg/kg, SC) or saline. Administration of COCA resulted in longterm significant changes in heart and breathing rates and spontaneous EEG (desynchronization in the occipital cortex and slow rhythmic theta activity in the hippocampus), inhibition of animal responses to noxious electroshock stimuli and modification in different amplitudes of evoked responses (mainly in the cortex, the enhancement of negativity and bidirectional changes in late slow phase). Principally identical but more or less changes were observed in response to administration of saline. Obtained results are discussed in respect to their interrelations with the general activation organism's response and the modification of brain metabolism induced by cocaine in restrained rabbits. PMID- 1938131 TI - Handedness and maternal smoking during pregnancy. AB - Nonright-handedness (NRH) has been attributed to hypoxia-induced brain changes in the fetus and associated pregnancy and birth complications (PBCs). Maternal smoking during pregnancy is known to produce prenatal hypoxia for the fetus, which may result in low birth weight and other PBCs. It was hypothesized that maternal smoking during pregnancy results in a leftward shift of handedness in the offspring. This study compared the distribution of handedness in the offspring of mothers who did and did not smoke cigarettes during pregnancy. Information on maternal smoking, handedness, and PBCs was analyzed for 803 university students. There was a significant shift to the left in the distribution of handedness scores for the offspring of smoking mothers (N = 216), as compared to those of nonsmoking mothers (N = 587). Offspring of smoking mothers also reported significantly more PBCs. Results are consistent with the hypothesis that NRH is associated with pathological neurodevelopment. PMID- 1938132 TI - The dual nature of lateral eye movements. AB - This study investigated the validity of lateral eye movements (LEM) as a measure of the individual differences and task demands aspects of LEM by comparing eye movements to information questions that had no clear hemispheric locus with eye movements to rhyme questions that demanded specific left hemisphere involvement. Fifty subjects were asked to respond to the two types of questions and the initial direction of their eye movement was recorded. The results indicated that LEM are a reliable measure of individual differences because both test-retest and split half reliabilities were high (.78 to .85). LEM were also shown to be responsive to task demands. The number of leftward LEM did not differ from rhyme and information questions, but there were more rightward LEM and fewer stares to the rhyme question. These results suggest that LEM are a reliable individual difference measure and are sensitive to task differences. There is clear evidence that LEM have neuropsychological implications, but every task demands the integrated functioning of the whole brain and these implications should not be overgeneralized. PMID- 1938133 TI - Analysis of task demands in apraxia. AB - Several task demands were examined in a battery of praxis tests: the movement system (limb versus axial), input modality (command versus imitation), movement complexity (single gestures versus a sequence of gestures), type of limb gesture (transitive versus intransitive), and the representational nature of the gestures. Performance accuracy for a group of left hemisphere patients was significantly lower than for two other groups of patients with either right hemisphere damage or no brain damage on all gestures. The right hemisphere patients were significantly different from the normals only for the most complex gestures involving a three movement sequence. Within the left hemisphere group performance to command was not different from imitation. Representational and nonrepresentational gestures were not different, and axial gestures was not different from the limb gestures. The transitive and complex gestures were not different but were both performed less accurately than the intransitive gestures. The implications of these findings for understanding apraxia were discussed. PMID- 1938134 TI - The effects of testosterone on paw preference in adult cats. AB - The effects of testosterone on paw preference assessed by a food reaching test was studied in adult cats. It was found that tetosterone propionate injected intramuscularly reduced the degree of the right-paw preference in right-preferent female cats. The paw preference of the male cats and left-preferent female cats was not affected by this male sex hormone. It was concluded that testosterone may especially suppress the left brain to induce ambilaterality in right-paw preference in adult female cats. PMID- 1938135 TI - The relationship between serum testosterone level and visuomotor learning in right-handed young men. AB - The relationship between serum testosterone level and visuomotor of learning of hand skill was studied in right-handed young men. Hand skill was assessed by a peg moving task. Peg moving times for the right and left hands linearly decreased at each successive trial (visuomotor learning). The peg moving times for the right and left hands were found to be negatively linearly related to serum testosterone levels: there was a direct relationship between hand skill and testosterone, which was more prominent for the right than the left hand. The slopes of the learning curves for the right hand were found to be equal in subjects with low, normal, and high testosterone. The intercepts of these curves exhibited a shift toward a better hand skill from low- to high-testosterone subjects. The visuomotor learning for the left hand was found to be better in subjects with normal and high testosterone than those with low testosterone. It was concluded that testosterone would favor the visuomotor development especially of the left cerebral hemisphere, probably at puberty; the motor learning of this hemisphere does not seem to be associated with testosterone. Testosterone seems to be advantageous for the visuomotor performance as well as for the motor learning of the right cerebral hemisphere. PMID- 1938136 TI - Development of voltage-dependent ionic currents in rat cerebellar granule cells grown in primary culture. AB - In this work we studied the excitable properties of cerebellar granule cells grown in primary culture in the presence of "high" KCl (25 mM). Whole cell patch clamp records of currents were obtained from cells at 1-33 days in culture (DIC). Sodium currents, blocked by TTX, were present from the first DIC and did show slow developmental changes. Two types of potassium currents were detected at all DIC: a delayed rectifier current (IK) and an inactivating current (IA). Both IK and IA increased until 7 to 9 DIC (four and two times respectively). Most of the IA increase, however, correlated with an increase in cell size, monitored by measurements of cell membrane capacitance (Cm) and the current density thus did not change. Conversely, delayed rectifier potassium current density did increase in the initial DIC (3-6) and did not change significantly after this time. Calcium currents were not detectable at any DIC under our experimental conditions. PMID- 1938137 TI - Analgesic nitrous oxide in alcohol withdrawal: the role of melatonin. PMID- 1938138 TI - "Down regulation" of 5-HT2 receptors: possible role of melatonin and significance for negative schizophrenia. PMID- 1938139 TI - Determination of the number and waveshapes of event related potential components using comparative factor analysis. AB - This paper applies new factor analysis methods to determine empirically the number and waveshapes of ERP components. It addresses several well-known problems in previous applications of factor analysis or principal components analysis (PCA) to ERP data, such as the assumption of simple structure by varimax rotation, low noise levels required by PCA, response latency variation, and background EEG (correlated noise). ERPs are modeled as consisting of nonstationary (response) components, stationary (random-phased EEG) processes, and independent noise. The analysis indicated that there was one main response component for the datasets analyzed, and that the EEG processes accounted for a major portion of the variance. Response components corresponded to the first and second derivatives of the dataset mean. This finding is due to response latency variation. Once the number and waveshapes of ERP components have been determined, source localization methods can be applied with much greater accuracy. PMID- 1938141 TI - Testosterone and artistic talents. AB - Musical composers, instrumentalists, and painters were compared with nonmusicians from a student and from an nonstudent population on testosterone levels in saliva. This steroid served as a marker for physiological androgyny. The ANOVA showed a significant group by sex interaction. Male composers attained significantly lower mean testosterone values than male instrumentalists and male nonmusicians; female composers had significantly higher mean testosterone values than female instrumentalists and female nonmusicians. Painters of both sexes did not differ significantly from controls. Spatial ability was assessed in the five groups. Significant differences on spatial test performance were not reflected in differences on salivary testosterone. Our results showed that musical composers of both sexes were physiologically highly androgynous. Creative musical behavior was associated with testosterone levels that minimized sex differences. PMID- 1938140 TI - Computer tomography in children with electrophysiological abnormalities. AB - A computed tomography examination was carried out in a group of 43 children, of whom 15 had learning disabilities (LD). Children were selected with electrophysiological abnormalities in the routine EEG, in the quantitative EEG analysis and/or in the visual cortical and auditory brainstem evoked responses. Seven children, 1 control and 6 LD, had abnormalities in the computed tomography. The most frequent localization of the lesion was the left temporal lobe. This localization might explain the origin of the learning disorder, since the left temporal lobe is involved in reading and writing processes. There was a great concordance between the anatomical localization of the lesion by the computed tomography and the place of electrical abnormalities in the quantitative EEG and the visual evoked responses. These results strongly support the indication of a computed tomography examination in LD children. PMID- 1938142 TI - Excitability and susceptibility of the brain's electrical activity during sleep: an analysis of late components of AEPs and VEPs. AB - We investigated ten healthy male subjects and measured late components of AEPs and VEPs during sleep. According to Rechtschaffen and Kales (1968) we performed an off-line scoring procedure of sleep-EEG and averaged the AEPs and VEPs of five different periods, corresponding to sleep stages I, II, III, IV and REM. From the averaged evoked potentials we computed the amplitude-frequency-characteristic (AFC) of the brain (Basar, 1980) during different sleep stages. These AFCs characterize transfer properties of an oscillating system. A comparison of different AFCs has shown that the excitability of the brain depicts a clear alpha resonance during stage I, a pronounced delta resonance during stages II, III and IV, and a theta resonance during REM sleep. A comparison of these results from linear system theory with the nonlinear dynamical behavior of the CNS was performed. PMID- 1938144 TI - Absence of neural responses following suppression of the immune response by cyclophosphamide. AB - Injection of sheep red blood cells (SRBC) as an antigenic stimulus, causes significant increases (up to 300%) in multiunit neural activity in the preoptic area/anterior hypothalamus of conscious rats. This increase occurs on the fifth or sixth day after immunization, at the time of first appearance of circulating antibodies at a serum titer of 1:32, increasing to 1:128 by day 10 following sensitization. Treatment with the immunosuppressive drug cyclophoshamide was able to prevent both antibody production and the expected increases in electrical activity in 5 of 6 rats; the one remaining animal showed a low level of circulating anti-SRBC antibodies on day 10 (1:32) and also, a small increase (36%) in neural activity at the expected time. These results provide further evidence that activation of the immune system is able to alter neuronal activity in an area of the brain important in the regulation of both neuroendocrine and neuroimmunomodulatory mechanisms, and that such activity is probably due to soluble secretory products released from components of the immune system. PMID- 1938143 TI - P2 latency of the flash visual evoked potential in dementia. AB - P2 latency of the flash visual evoked potential was found not to be prolonged in 13 demented patients compared to age normative predictions derived from a control group. This finding contrasts with a number of studies of demented patients that found P2 latency to exceed normative data. It was stated that the result of normal latency in dementia can hardly be explained only in terms of the sampling method used in this study (unselected dements) and that the finding is possibly due to the increase in latency across the adult life span in normal aging which was found to be much higher than previously reported. PMID- 1938145 TI - Asymmetrical effects of cortical ablation on brain monoamines in mice. AB - Neurochemical changes induced by right or left cortical ablation which have previously been described to have immunological effects were investigated in mice. Catecholamine and indolamine levels were determined in the contralateral cortex and in subcortical structures involved in immunoregulation 14 and 60 days after unilateral cortical ablation. Unilateral cortical ablation induced profound and widespread changes in the contralateral cortex but also in subcortical regions of both sides at 14 days after surgery. Lesions of the left neocortex appeared mainly to affect the activity of serotoninergic inputs to the right neocortex, whereas ablations of the right cortex influenced the activity of the catecholaminergic inputs to the left. Sixty days after surgery, modifications in monoamine levels were observed only in the ipsilateral, but not contralateral, subcortical regions, the only exception being that DA turnover in the tuberoinfundibular system remained lowered in both hemispheres after either right or left cortical ablations. Furthermore, some asymmetrical effects of cortical lesions depended on functional brain lateralization as assessed by paw preference. It may be hypothesized that some neurochemical modifications induced by unilateral cortical lesions are, at least partially, responsible for the immunological perturbations observed after cortical ablation. PMID- 1938146 TI - Digital vision theory: Boolean logic model. AB - Guild (1932) stated the general requirements for processing signals in color vision system and a digital format of his paradigm is developed in this paper. The disk structure generates the digital receptor pulse. The input modalities form sets, linked by intersections, joins, and complement junctions. The synapses are elements in these junctions. Complex synapses form complex junctions to create Boolean logic processing. A computer program using these Boolean logic functions calculates: Light and dark adaptation responses; Color matching and spectral coordinate functions; Chromatic adaptation and color shift responses; and dynamic neural responses. These calculations compare favorably with the experimental data. PMID- 1938147 TI - Induction of plasticity in the isolated spinal cord in paraplegia. AB - In adult life a severe injury of the spinal cord results in total loss of locomotor functions of the hind limbs, i.e., paraplegia. However, after similar injury in neonatal life most hind limb functions are retained unaffected into adult life. Can such survival of locomotor function be produced in an adult paraplegic? Observations based on our previous studies suggest that sparing of function in the neonate is due to: 1) incomplete development of descending cord tracts 2) the presence of polyneuronal control of limb muscles by spinal motoneurons and 3) active growth of synaptic connections occurring in the cord while limbs are polyneuronally innervated. Such growth and remodelling ceases once mononeuronal (= adult) control of limb muscles is established. We suggest that recreation of conditions similar to neonatal life would be able to revive lost locomotor functions in the adult paraplegic. Experimental animal models are outlined here which may form a basis for future research. PMID- 1938148 TI - Hoffmann reflex from foreleg flexor nerves in cats: lateralization, picrotoxin, strychnine, crossed flexor reflex. AB - Hoffmann (H) reflexes from foreleg flexor nerves were studied in cats. The right and left flexor nerves were stimulated and H reflexes were recorded from the same nerves. Paw preference was assessed by a food reaching test. Stimulation of the right median nerve elicited mono- and polysynaptic reflexes from the left ulnar nerve (crossed flexor nerve). Picrotoxin depressed, and strychnine increased H reflexes from both sides without affecting the spinal motor asymmetry. H reflexes were found to be larger on the left than the right side in right-preferent cats and vice versa in left-preferent cats. The right H-reflex recovery curve was higher than left in right-preferent cats. The inhibitory period of the recovery cycle disappeared after picrotoxin and changed to facilitation for the nonpreferred side. Strychinine caused bilateral, nearly-synchronous motoneuronal discharges from the right and left flexor nerves; the discharges originating from the left side preceded those from the right side in a right-preferent cat. These results indicate that spinal motor activity predominates on the nonpreferred side, which would be a prerequisite for postural adjustments during paw use in cats. This asymmetric motor organization in the forelegs of cats having quadrpedal locomotion seems to be similar to asymmetric motor organization in legs in humans. PMID- 1938149 TI - Oxygen free radicals and brain dysfunction. AB - Oxygen free radicals, any chemical moiety containing an oxygen atom with an unpaired electron in the outer orbital shell, are generated during many normal biochemical reactions in living tissue. The unpaired electron makes these compounds highly reactive and they can initiate disruptive peroxidation reactions with various substrates important to the survival of cells such as proteins, lipids and nucleic acids. A fairly complex defense system has evolved to protect living tissue from free radicals and to minimize the damage they might cause. Neurons are especially vulnerable to free radical attack and impaired defenses or exposure to excess free radicals can lead to neuronal death. Free radicals contribute to neuronal loss in cerebral ischemia and hemorrhage and may be involved in the degeneration of neurons in epilepsy, schizophrenia, tardive dyskinesia, normal aging, Parkinson's Disease and Alzheimer's Disease. The development of drugs that limit or prevent the attack of free radicals on neurons would be an important advance in the treatment of these conditions. PMID- 1938150 TI - Electrophysiological correlates of auditory lexical decision: an attempt to test the "Cohort Model". AB - The electrophysiological correlates of spoken word recognition were investigated in an auditory lexical decision task. N4 and P7 waves were found at Cz and Pz for both words and nonwords, with significantly higher peak amplitudes for the latter; this result was independent of subject's sex and of hand usage for the task response. The results were then analyzed in terms of the "Recognition Point" for words and nonwords as defined in Marslen-Wilson's "Cohort Model" of auditory word recognition (Marslen-Wilson & Welsh 1978). A correlation was found between nonword "Recognition Point" latency and the associated late positive wave. The contribution of the "Cohort Model" to electrophysiological investigation of auditory word-recognition is discussed. PMID- 1938151 TI - Focal dorsal raphe stimulation and pinnal electrical stimulation modulate spontaneous and noxious evoked responses in thalamic neurons. AB - This study investigated the nocieceptive responses of single neurons within the nucleus parafascicularis (PF) thalami of the rat following two modes of electrical stimulation known to induce analgesia. It was found that both focal electrical dorsal raphe stimulation (DRS) and bilateral pinnal (ear) electrical stimulation (PES) converge on the same PF neurons, affecting both the spontaneous discharges and the noxious evoked responses toward these neurons. The effects of different stimulus current intensity, frequency and pulse duration were also examined. It was found that for both DRS and PES at pulse frequency of 10 Hz and current amplitude of 10 microA are the optimal parameters to modulate both the spontaneous and the noxious evoked responses. These stimuli produced prolonged effects related to the duration of stimulation. The external (PES) low current stimulation which was delivered below the sensory threshold was as effective in modulating noxious responses as the invasive DRS in intact animals and in animals with bilateral dorsolateral-funiculus ablation. It was observed that dorsal lateral funiculus ablation (DLFx) did not modify the DRS and the PES effects. These observations further support the existence of an ascending pain modulation pathway. PMID- 1938152 TI - Immunological and behavioral effects of fragrance in mice. AB - The aim of this study was to determine the effects of olfactory stimulation on immunological and behavioral states in mice. Anti-SRBC (IgM) plaque forming cell (PFC) count and spontaneous running activity (SRA) were measured to demonstrate the effects of exposure to a given fragrance. The decreased PFC count and thymic involution induced by high pressure stress in mice were recovered after exposing the stressed mice to the fragrance continuously for 4 days after the stress was given. The PFC and SRA also appeared to be maintained at normal levels by oflactory stimulation with the fragrance for 24 hrs after the given stress. The immunological suppression induced by high pressure stress was considered to be caused by the induction and activation of suppressor cells. However, exposure to the fragrance after the stress did not enhance suppressor activity. The restoration of the stress-induced immune suppression by olfactory stimulation was blocked by procain administration onto the olfactory cells. PMID- 1938153 TI - Efferent gating of human auditory attentional processes. AB - Brainstem evoked potentials were measured while subjects reduced either frontalis or lips/throat activity in response to visual information regarding EMG activity while attending to dichotically presented click stimuli. An inhibition of left ear activity occurred at the level of the cochlear nucleus (Wave 1) during articulatory muscle activity, suggesting that the right ear advantage is related to active inhibition of ipsilateral auditory pathways. Contralateral central inhibition of disattended information at the level of the brainstem (Wave 5) was also implicated. A neurophysiological model accounting for both attenuation of irrelevant stimuli and vigilance for high priority information is proposed. PMID- 1938155 TI - Brain imaging in dementia of the Alzheimer type. AB - Neuroimaging modalities have increased understanding of brain abnormalities in dementia of the Alzheimer type (DAT), and is important in assessment of dementia syndromes by revealing focal disorders, demonstrating potentially treatable conditions, and by documenting progression of disease severity. Computed tomography (CT) and magnetic resonance imaging (MRI) have delineated structural changes in DAT, including cerebral atrophy associated with cortical sulci widening and ventricular enlargement, and deep white-matter lesions with periventricular distributions. Positron emission tomography (PET) has demonstrated diminished regional glucose metabolism at parietal and temporal lobes in DAT, while frontal hypometabolism tends to occur in more severe cases. Metabolic dysfunction assessed by PET appears to be the first indication of a degenerative cortical process in DAT, while anatomic changes on CT or MRI may become evident later in the disease process. This selective overview provides an analysis of the current status and future prospects of brain imaging in DAT. PMID- 1938154 TI - Formant movement and formant number alteration with rising FO in real vocalizations of the German vowels [u:], [o:] and [a:]. AB - Production theory explains vowel sounds by formants in terms of a resonance pattern of the vocal tract. In perception theory normalization must also be undertaken because of different formant values for one vowel category, as found in comparisons of men, women and children, and in studies of sung vowels and of synthesized vowel sounds. Synthesis indicates a dependence of the formants on FO. Therefore, the question arises whether the formant pattern is directly related to FO when studied in real vocalizations. This study presents: a. a method to determine formant movement in real vocalizations for all FO, and b. the results of spectral and LPC analysis of the three German vowels [u:], [o:] and [a:] in real vocalizations. The need for formant movement with altering FO, as well as a change in the number of formants with altering FO, is demonstrated. The implications of these results for normalization in the description of the physics of the vowel sound wave are discussed. PMID- 1938156 TI - The relationship of latency characteristics of the Hoffmann reflex from the right and left thenar muscles to serum testosterone levels in right-handed male and female subjects. AB - The latency characteristics of the Hoffmann reflex from the right and left thenar muscles were analyzed in right-handed young men and women relative to serum testosterone levels. There was no correlation between the H-reflex latencies and serum testosterone levels in the female subjects. In the male subjects, the H reflex latencies from the right and left sides were found to be negatively linearly related to the serum testosterone levels. The right minus left latencies were found to be inversely correlated with serum testosterone levels in women; there was no correlation between these variables in men. It was also established that the right-left differences in the H-reflex latencies were directly related to the degree of the right-hand preference in the female subjects. It was concluded that testosterone may, at least, contribute to the spinal-motor lateralization in women, but not in men. The results were also discussed with regard to the testosterone hypothesis of cerebral lateralization, sex-related differences, hand preference, hand skill, and intelligence. PMID- 1938157 TI - Neuropsychological deficits in chronic cocaine abusers. AB - A basic neuropsychological assessment battery was given to thirty-seven chronic freebase cocaine ("crack") abusers. The following tests were used: Wechsler Memory Scale (Wechsler, 1945), Rey-Osterrieth Complex Figure (Osterrieth, 1944) (copy and immediate reproduction), Verbal Fluency (semantic and phonologic), Boston Naming Test (Goodglass, Kaplan, & Weintrab, 1983), Wisconsin Card Sorting Test (Heaton, 1981) and Digit-symbol from the WISC (Wechsler, 1974). In general, performance was lower than expected according to their age and educational level. Subjects showed significant impairment in short-term verbal memory and attention subtests. Neuropsychological test scores were correlated with lifetime amount of cocaine used, suggesting a direct relationship between cocaine abuse and cognitive impairment. A pattern of cognitive decline is proposed. PMID- 1938158 TI - The effects of iron deficiency and electric shock on learning in rats. AB - It is hypothesized that electric shock can compensate for the learning deficit caused by iron deficiency in the experimental rat population, and that this effect will be sustained over a 3-week "rehabilitation" period. Forty-seven female Sprague-Dawley rats served as the experimental subjects. The learning capacity of the rats was assessed using a water Y-maze. The dependent variables were assessed twice, once after half had been made iron deficient, and again after the iron deficiency had been corrected. A 2 x 2 x 2 analysis of variance with repeated measures was employed, along with post-hoc tests, to assess the effects of the experimental manipulations on the rats' performance. The experimental results replicated previous findings regarding the damaging effects of iron deficiency on learning capacity in rats and confirmed that shock improves the performance of rats in the water Y-maze. Furthermore, it was found that shock and iron deficiency interact, such that the performance of iron-deficient rats subjected to electric shock is superior to that of rats not made iron deficient. This trend persists even after the hematological effects of iron deficiency are corrected, although to a less dramatic degree. A possible explanation for these findings is advanced. PMID- 1938159 TI - Choroid plexus calcification: a biological marker of suicidality. PMID- 1938160 TI - Use of brief cognitive tests to identify individuals in the community with clinically diagnosed Alzheimer's disease. AB - Two brief screening tests, the Short Portable Mental Status Questionnaire (SPMSQ) and the East Boston Memory Test (EBMT), were included in a population questionnaire administered to 3,811 persons 65 years of age and older. A detailed clinical evaluation was then administered to 467 persons (drawn from high, medium and low performers on the EBMT) to determine who was cognitively impaired and the disorders that were responsible for that cognitive impairment. The results showed that the EBMT was better at enriching the population of the poor performance group with persons who had Alzheimer's disease (AD). It had a lower refusal rate among non-proxy respondents: 2% for the EMBT versus 9% for the SPMSQ. The sensitivity and positive predictive value were also higher for the EBMT than the SPMSQ when the diagnosis of interest was AD. However, there were persons with AD in all strata of performance on both the EBMT and the SPMSQ, emphasizing the importance of selecting persons from all performance strata in multistage community studies of AD. PMID- 1938161 TI - The relationship of pineal calcification to cortical atrophy in schizophrenia. AB - Several recent computed tomographic (CT) studies have provided evidence for structural cerebral abnormalities in schizophrenia. CT scan findings included enlargement of the lateral cerebral ventricles, cortical atrophy, third ventricular dilatation, ventricular asymmetry, and cerebellar atrophy. In addition, there is increasing data to suggest that abnormal pineal melatonin functions are associated with the pathophysiology of schizophrenia. To explore further the relationship of the pineal gland to the pathophysiology of schizophrenia and its specific association with structural abnormalities, we investigated: (a) the relationship of pineal calcification (PC) to computerized tomographic (CT) scan measurements of cortical and subcortical atrophy in 41 chronic schizophrenic patients, and (b) the relationship of PC size to CT scan measurements and cortical and subcortical atrophy in 51 chronic schizophrenic patients. Results of the first study revealed that the presence of PC was significantly associated with measurements of prefrontal cortical atrophy (p less than .01), while there was no association with measurements of parieto-occipital atrophy, sulcal prominence, or ventricular brain ratio (VBR). These findings support the notion that the various structural brain abnormalities in schizophrenia may reflect different pathological processes and that abnormal pineal melatonin functions may be associated with the pathophysiology of prefrontal cortical atrophy. In addition, since some clinical facets of schizophrenia covary with frontal lobe dysfunction, our findings highlight the significance of abnormal pineal functions for the pathophysiology of schizophrenia. In the second study we found a significantly higher prevalence of pathologically enlarged PC (i.e., greater than 1 cm in diameter) in schizophrenia as compared to controls of similar age. In addition, we found a significant association between CT scan measurements of cortical atrophy and pathologically enlarged PC size (p less than .05). By contrast, PC size was unrelated to VBR. These findings demonstrate a specific association between pathologically enlarged PC and cortical atrophy in schizophrenia. The implications of these findings to the pathophysiology of schizophrenia and, specifically, to the morphological abnormalities that accompany the disease are discussed. PMID- 1938162 TI - Reinforcing properties of morphine chronically used in aversive life conditions: place-preference paradigm, long-term changes in behavioral reactivity. AB - To substantiate significance of the organism's functional state in the mediation of an opiate's reinforcing activity, the rats' attitude to an initially nonpreferred environment associated with chronic (10) administration of morphine (MOR 0.67 and 2.0 mg/kg) was regularly estimated after drug administrations in conditions of two-hour restraint stress. The absence of any significant changes in the quantity of entries and the time in restraint box in rats received MOR at a low dose and only a slight increase in the quantity of entries found in animals administered MOR at a high dose allowed us to propose a blockade or prominent inhibition of the drug's rewarding efficacy to be typical under these conditions. Inverted changes in movement reactivity (its increase) as response to apomorphine at low "presynaptic" doses found in animals treated by MOR may indicate the involvement of modified presynaptic dopamine receptors in the mediation of revealed changes in an opiate's reinforcing activity. PMID- 1938163 TI - Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia. AB - Degeneration of the cerebellar vermis is a common pathological and neuroradiological feature of chronic schizophrenia, but its relationship to symptoms of the disease are poorly understood. We investigated the relationship of vermal cerebellar atrophy on CT scan to features of positive (productive) and negative (defect) dimensions of schizophrenia as well as to symptoms of general psychopathology in a sample of 23 chronic schizophrenic patients. For comparison, we also studied the relationship of third ventricular width (TVW), which reflects periventricular and diencephalic atrophy, to these features of schizophrenic symptomatology. Vermal cerebellar atrophy was found in 43.5% of patients and correlated significantly with general psychopathology and, more specifically, with feelings of guilt and disturbance of volition. It was unrelated to global positive or negative features of schizophrenia. By contrast, TVW was uniquely associated with global negative syndrome. These observations indicate that degeneration of the cerebellar vermis and enlargement of the third ventricle are integral aspects of schizophrenia, and that each contributes independently to specific clinical aspects of the disease. PMID- 1938165 TI - The inverse relationship between nonverbal intelligence and the latency of the Hoffmann reflex from the right and left thenar muscles in right- and left-handed subjects. AB - The relationship between nonverbal reasoning ability and the latency of the Hoffmann (H) reflex was studied in right- and left-handed subjects. The nonverbal reasoning ability was assessed by the Cattell's Culture Fair Intelligence test. Hand preference was assessed by the Edinburgh Handedness Inventory. Hoffmann reflex was recorded from thenar muscles of the right and left thumbs. In left handers (total sample), IQ was found to be significantly and negatively linearly related to the H-reflex latency from the left side. In strong left-handers, there was a significant negative linear relationship between IQ and the H-reflex latency from right and left sides, but with a higher correlation for the left side. In weak left-handers, IQ did not show any significant relation to the H reflex latencies from the right and left sides. In right-handers (total sample), there was a significant negative linear correlation between IQ and the H-reflex latency from the right side. In right-handed women without familial sinistrality (FS-), IQ was found to be inversely related to the H-reflex latency from the right and left side, but with a higher correlation for the right side. In right handed women with FS, IQ did not show any significant relation to the H-reflex latency from the right and left sides. In right-handed men with right eye preference and FS-, IQ was found to be negatively linearly related to the H reflex latency from the right and left sides equally. In right-handed men with right eye FS+, mixed eye FS-, +, mixed eye-right foot (FS-), mixed eye-mixed foot, and left eye preference there was no significant relationship between IQ and the H-reflex latency from the right and left sides. Only in strong left handers there was a significant, positive linear correlation between IQ and the right minus left (R-L) difference of latencies. The H-reflex latency from the right and left sides was not significantly correlated with the R-L difference of latencies in left-handers. In right-handed women with right eye preference FS-, and in right-handed men with right eye preferences FS-, The H-reflex latency from the right side was found to be positively linearly correlated with the R-L difference of latencies. In right-handed women FS+, and in right-handed men FS+, and mixed or left eye preference, the H-reflex latency from the left side was found to be negatively linearly related to the R-L difference of latencies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1938164 TI - Facilitation of spike-wave activity by the hypnotic etomidate in a rat model for absence epilepsy. AB - The epileptogenic effect of the short-acting hypnotic agent etomidate was investigated in WAG/Rij rats. Animals of this inbred strain show spontaneous spike-wave discharges and are regarded as a model for absence epilepsy. A dose dependent increase in the total amount of spike-wave activity was found, when etomidate was injected intraperitoneally in doses of 1, 2.5, 5 and 10 mg/kg. At a dose of 10 mg/kg, spike-wave activity appeared almost uninterruptedly. Beginning with a dose of 5 mg/kg, the morphology of the spike-wave complexes changed after the administration of the drug; spike frequency decreased dose dependently from about 8 till about 4 Hz at 10 mg/kg. During spike-wave activity, animals were motionless and, certainly at 10 mg/kg of etomidate, were unresponsive to stimuli. For surgical anesthesia, a still higher dose of etomidate is necessary (20 mg/kg). It is concluded that etomidate facilitates the generation of spike-wave activity in rats with spontaneous absence seizures, presumably through its GABA mimetic action. PMID- 1938166 TI - The effects of unilateral forced nostril breathing on cognition. AB - Ultradian rhythms of alternating cerebral dominance have been demonstrated in humans and other mammals during waking and sleep. Human studies have used the methods of psychological testing and electroencephalography (EEG) as measurements to identify the phase of this natural endogenous rhythm. The periodicity of this rhythm approximates 1.5-3 hours in awake humans. This cerebral rhythm is tightly coupled to another ultradian rhythm known as the nasal cycle, which is regulated by the autonomic nervous system, and is exhibited by greater airflow in one nostril, later switching to the other side. This paper correlates uninostril airflow with varying ratios of verbal/spatial performance in 23 right-handed males. Relatively greater cognitive ability in one hemisphere corresponds to unilateral forced nostril breathing in the contralateral nostril. Cognitive performance ratios can be influenced by forcibly altering the breathing pattern. PMID- 1938167 TI - Cannabis and cerebral hemispheres: a chrononeuropsychological study. AB - This work is a study of the possibility that chronic consumption of derivatives of cannabis can affect the cognitive styles and the brain, altering the relations between both cerebral hemispheres. The results indicate that the Basic Rest Activity Cycle (BRAC) between two different cognitive styles is not altered in the subjects of the control group; however, there is an alteration in the BRAC of the cerebral hemispheres in the chronic users of hashish. PMID- 1938168 TI - Tobacco addiction as a marker of age at onset of schizophrenia. AB - Schizophrenia is a heterogenous disorder, with diversity in symptoms, course, prognosis, and probably etiology. The timing of its onset (i.e., early vs. late) not only predicts outcome of illness, but also corresponds to fundamental neurochemical and neuroendocrine distinctions. There is recent evidence that early age at onset of schizophrenia is associated with more prominent negative symptoms, which are associated with decreased dopaminergic functions in the limbic system. Since addictive behaviour may be related to decreased dopamine activity in the mesolimbic reward circuitry, we predict a higher prevalence of tobacco addiction in patients with an earlier age at onset of schizophrenia. To investigate this hypothesis, we studied the association of cigarette smoking to age at onset of illness in a sample of 142 chronic schizophrenic inpatients, 73 of whom were smokers. We found that patients who smoked had a significantly earlier age at onset of psychiatric illness as compared to the nonsmokers (p less than .01). Since damage to dopaminergic systems at the lateral hypothalamic level of the medial forebrain bundle and in the ventral tegmental reward system produces the strongest indication of reward, our data suggest that alterations in dopaminergic functions in these systems may be linked to the timing of onset of schizophrenic symptoms. PMID- 1938170 TI - Suicidal behavior and tardive dyskinesia. PMID- 1938169 TI - Thyroid function in patients with chronic headache. AB - Headache is one of the neurological manifestations of hypothyroidism but it is unknown whether there is a relationship between hyperthyroidism and chronic headache. Thyroid function tests were performed in 30 patients with chronic headache. Six were found to have hyperthyroidism and none had hypothyroidism. Thyroid testing may be useful for differential diagnosis of chronic headache, and indicates that headache could be caused by hyperthyroidism. PMID- 1938171 TI - Dopaminergic involvement in the mediation of morphine effects on vocalization and movement reactivity in the rat. AB - To understand the role of dopamine in the mediation of opiate's analgesic and reinforcing activity, the influence of pharmacologically-induced increase (apomorphine in a high dose) and decrease (haloperidol and apomorphine in a low "presynaptic" dose) of dopamine neurotransmission on morphine-induced depression of vocalization and movement reactivity was investigated in freely behaving rats. Strong enhancement of morphine-induced vocalization reactivity depression and a weakening of movement reactivity depression typical to concomitant pharmacological increase of dopamine neurotransmission may represent the enhancement of its reinforcing and analgesic properties and inhibition of its depressive/sedative activity. Enhancement of MOR-induced depression of movement and vocalization reactivity characteristic of drug-induced decrease of dopamine neurotransmission may be the consequence of the blockade of opiate's reinforcing and stimulatory activity and summation of depressive/sedative actions typical to these drugs administered alone. PMID- 1938172 TI - EEG and skeletal development in children with different psychosocial characteristics. AB - Two groups of children with different socioeconomic level were studied. One minute EEG at rest was recorded in monopolar leads F3, F4, C3, C4, P3, P4, O1, O2, F7, F8, T3, T4, T5 and T6. Absolute and relative power in four EEg bands (delta, theta, alpha and beta) were computed. Radiographies of the left hand and the wrist were also obtained in all children. Age regression equations of the variables derived from EEG spectra were calculated in each group. In the group with low socioeconomic level many children had antecedents of risk factors. In this group absolute and relative power in the four bands presented a great dispersion and no correlation with age. In the group with good socioeconomic level the age regression equations of the EEG variables were significant, absolute values in the four bands decreased with age, as well as delta and theta relative power, while alpha and beta relative power increased with age. The area of the ossification center of each bone of the hand of the lower end of the ulna and radius were obtained from the X-ray film. Linear regression equations for the area of each ossification center were significant in both groups. No intercept or slope differences existed between both groups in any area. It is concluded that psychosocial disadvantage and antecedents of risk factors, although not producing any effect on skeletal development, do affect EEG maturation. PMID- 1938173 TI - Brain-associated autoimmune features in heroin addicts: correlation to HIV infection and dementia. AB - We report here on brain associated autoimmune features in opiate-dependent subjects. This study includes 107 (37 HIV + and 70 HIV -) hospitalized heroin addicted subjects on a methadone maintenance program, and 45 healthy individuals. Human brain S100 protein, neuron specific enolase (NSE), myelin basic protein (MBF), and old tuberculin (OT) were used as antigens in the study. Serum autoantibodies to brain antigens S100, NSE and MBP were detected by ELISA, whereas delayed hypersensitivity skin reactions were evaluated after intradermal injection of S100, NSE, MBP and OT (control brain-irrelevant antigen). In drug dependent subjects, 68.2% produced anti-S100, 56.1% anti-NSE and 20.5% anti-MBP autoantibodies, while the incidence of autoantibodies in control healthy individuals was 4.4%, 2.2% and 0%, respectively. Occurrence and amount of anti S100 and anti-NSE autoantibodies were much higher in HIV + than in HIV - heroin abusing adults. In drug abusers, the incidence of positive delayed hypersensitivity skin reactions were as follows: 67.2% to S100, 51.4% to NSE, 14.9% to MBP, and 94.3% to OT. In control subjects, the occurrence of hypersensitivity reactions to brain antigens was insignificant. Cutaneous reactions were more frequent in HIV - addicts. The incidence of both autoantibodies and delayed skin responses was positively related to the duration of drug abuse, worsening of HIV infection, and dementia. The high incidence of autoantibodies and delayed hypersensitivity skin reactions to S100 and NSE human brain antigens in heroin-abusers indicates that heroin dependence, as well as HIV infection, are associated with a hyperergy towards brain-related autoimmune phenomena. It has been suggested that the brain-associated autoimmune phenomena in HIV + heroin-addicts represent a hyperimmune phase which precedes immunodeficiency that occurs in the further development of HIV infection. PMID- 1938174 TI - Pseudoneglect on a cancellation task. AB - The "pseudoneglect" phenomenon initially described by Bowers and Heilman (1980) was examined in the context of a cancellation task. Normal subjects were administered cancellation tasks under a high arousal condition with target and foils which were intended to activate left hemisphere (verbal) processes or right hemisphere (spatial) processes. Significant right lateralized inattention was present on the spatial stimuli. The verbal stimuli failed to produce significant lateralized inattention, although it produced moderate left inattention among right-handed males. The results are consistent with literature identifying the right hemisphere as dominant for attention. PMID- 1938175 TI - Experimental models of schizophrenia. AB - The Kraepelinian subtypes, developed early in the century, recognize the heterogeneity of schizophrenia but do not reliably predict differences in response to classical neuroleptics. The newer distinction of positive and negative syndromes in schizophrenia carry promise as an approach to identifying meaningful clinical and neurobiological dimensions. The present review summarizes the supportive evidence from a series of investigations using the Positive and Negative Syndrome Scale (PANSS), and a hypothesis on the pathophysiology of negative and positive symptoms is advanced. Our data suggest that: (a) positive and negative syndromes in schizophrenia represent stable, independent dimensions and not co-exclusive subtypes; (b) both are unrelated to the progression of illness; (c) they are differentially related to fundamental aspects of schizophrenia, including premorbid adjustment, cognitive development, family psychiatric history, the cognitive and neuropsychiatric profiles, dopaminergic functions, drug response, and subsequent course; (d) together with depression and excitement, they comprise the fundamental symptomatic components of schizophrenia, which, in their interaction, can account for the specific Kraepelinian subtypes. We have proposed that negative symptoms represent the core pathology in schizophrenia and may be understood as a variant of parkinsonism, hence characterized by dopaminergic deficiency and increased cholinergic activity. This view is supported by the striking overlap with Parkinsonism in regard to clinical features, neurochemistry, pharmacology, neuropathology, and neuroradiology. Positive symptoms are thought to reflect increased dopaminergic activity, which may arise as a compensatory adaptive mechanism to overcome the progressive dopamine loss in the maturing brain. The early onset of schizophrenia by comparison to Parkinson's disease may explain why schizophrenia entails more pronounced positive symptoms, development deficits, and cognitive, social, and emotional impairments. We describe evidence that pineal calcification, which may reflect disturbance of melatonin functions, appears to be a nongenetic factor in schizophrenia associated with perinatal injury. This may in part underlie the negative syndrome and its response to antipsychotic compounds with serotonergic (5-HT) antagonism. PMID- 1938176 TI - Neuroradiological covariates of drug-induced parkinsonism and tardive dyskinesia in schizophrenia. AB - Computed tomographic (CT) studies have demonstrated structural brain abnormalities including cortical atrophy and enlarged lateral ventricles in a subset of schizophrenic patients including those with abnormal involuntary movements. In the following series of studies, we present our findings pertaining to neuroradiological covariates of drug-induced Parkinsonism and Tardive dyskinesia in schizophrenic patients. In these studies we have explored the relationship of Parkinsonism and Tardive dyskinesia to pineal and choroid plexus calcification. In addition, we also investigated the relationship of pineal calcification to schizophrenia, and specifically to the paranoid and nonparanoid subgroups. In a further series of studies, we investigated the neuroradiological covariates of disorders of gait and posture as well as tremor in schizophrenic patients with drug-induced Parkinsonism. In addition, we explored the relationship of Tardive dyskinesia and its subsyndromes to CT scan measurements of cortical and subcortical atrophy in schizophrenia. Our findings highlight the significance of the pineal gland in the pathophysiology of schizophrenia and drug induced movement disorders. Furthermore, these studies underscore the heterogeneity of Parkinsonism and Tardive dyskinesia. PMID- 1938177 TI - Neuroradiological facets of cognitive abnormality in schizophrenia. AB - Cognitive abnormality has long been regarded as a core feature of schizophrenia, but its nature and etiopathology have been poorly understood. Predicated on new tests that characterize fundamental cognitive impairments, we investigated their relationship to four neuroradiological markers that have been previously implicated in schizophrenia: choroid plexus calcification, cerebellar atrophy, third ventricle enlargement, and pineal calcification. Twenty-three chronic schizophrenic inpatients meeting RDC and DSM-III diagnostic criteria were stabilized on chlorpromazine and assessed independently on a cognitive battery and on CT scan. The results indicated that all four neuroradiological variables were independent of one another and of demographic, historical, and general intellectual measures. The neuroradiological assessments, however, correlated significantly with different cognitive parameters, implying separate pathophysiological bases for distinct profiles of cognitive abnormality. The findings support a "dual-process model" of cognitive dysfunction that posits developmental and arousal-related components which may, more generally, underlie the positive-negative dimension of schizophrenia. PMID- 1938178 TI - Applications of three-dimensional analysis to the auditory P300. AB - Auditory Event Related Potentials (ERPs) to target stimuli were recorded by three orthogonal derivations from 18 normal subjects and were represented in three dimensional voltage-space (3-D), to produce Three Channel Lissajous' Trajectories (3CLTs). Target stimuli differed by pitch, phonemic or phonetic attributes. Assuming a central location, the orientation of the equivalent dipole moment was calculated for specific points (apices) along the trajectories. The apices roughly corresponded to the P300 peak in a voltage/time representation. The 3-D analysis resulted ina dipole pointing in a posterior-upward direction close to the mid-sagittal plane. Based on anatomical measures coupled with the behavioral role of the limbic system, we propose that a major contribution to the P300 to the stimuli tested derives from the outflows of the hippocampus and amygdala, i.e. fornix and stria terminalis. Orientation and laterality of the P300 dipole demonstrated clinical sensitivity beyond that of latency and amplitude measures in voltage/time representations. PMID- 1938179 TI - An intercultural assessment of the type, intensity and number of crisis precipitating factors in three cultures: United States, Brazil and Taiwan. AB - The precipitating factors of crisis have cultural interpretations that make diagnostic criteria and intervention methods ethnologically different. The crisis precipitating factors of individuals seeking intervention in the Republic of China (Taiwan), Brazil and the United States (U.S.) were investigated toward the end of isolating correlates and discrepancies of ethnic-related precipitants of crisis. The primary objective of the study was to influence crisis intervention in the profession of nursing from the almost universally utilized Western Model, to one that takes cultural uniqueness into account. Stressors and stressor intensities which lead to help-seeking behavior of clients in selected crisis intervention facilities in the three countries were identified. A 60 question instrument ranked client responses according to Axis 4 of the Diagnostic and Statistical Manual-III of the American Psychiatric Association (APA, 1980; 1986). Each item also reflected one of four Human Response Patterns of the North American Nursing Diagnostic Association (NANDA) taxonomy, which was utilized as a clustering device in data analysis. Somatization versus psychologization of crisis precipitating factors was also measured through the NANDA categories. A convenience sample of 30 subjects were queried in each country by nurse interviewers. Data analysis through ANOVA showed cultural uniqueness and mutuality. PMID- 1938180 TI - Generating research in mental health nursing. AB - This paper explores a number of areas for research development in mental health nursing in the United Kingdom. Several potential areas are identified: historical research, policy related research, the role of mental health nurse as a provider of a therapeutic milieu, as therapist and as teacher. Academic centres are identified in mental health nursing research and a plea is made for the preservation of valuable archive data being lost as mental hospitals are closed. Nurse leaders in mental health nursing are encouraged to make particular provision for research activity. PMID- 1938181 TI - Effects of reduction of acute hospital services on district nursing services: implications for quality assurance. AB - Two questions of importance to those concerned with maintaining standards and increasing the efficiency of Community Nursing are: (1) does reducing hospital provision alter the number of patients referred for Community Nursing or the type of care provided; (2) are Community Nursing Services directed towards those who most require them? A base-line study was carried out in the first quarter of 1988, before the closure of one of two general hospitals in an inner London Health Authority and was replicated in the same quarter of 1989, after all acute inpatient services had been transferred to the other hospital. Comparison of patients discharged before and after closure showed no significant differences in patients' age, sex, proportion living alone, length of stay in hospital, readmissions or deaths within one month of discharge. There was some decline in general nursing care. Total discharges declined by 20% while the number of referrals remained the same, indicating that proportionately more patients were discharged with a referral. Comparing referred and unreferred patients showed that Community Nursing Services were already being directed towards those most in need both before and after hospital closure. Results suggest that Community Nursing helps to maintain patients in the community. PMID- 1938182 TI - Where are they now? The career paths of graduates from post-registration degrees in nursing in England. AB - Degree courses for experienced nurses through part-time study are relatively new in Britain. The first course started in 1979, but their number has dramatically increased during the past decade, particularly in England. Due to this increase it is important that analysis of career paths of the graduates should occur. As no suitable questionnaire was found from the literature one was devised. Posting this to all graduates from three courses gave a response from 113 graduates (77.4%). Results showed graduates to be continuing in nursing. They showed life long motivation to study and felt personal growth from the degree. Movement of graduates predominantly from clinical areas into nurse education was found. PMID- 1938183 TI - The importance of nurse caring behaviors as perceived by Swedish hospital patients and nursing staff. AB - The present study identified patient (n = 81) and nursing staff (n = 105) perceptions of the most and least important nurse caring behaviors. Using a Swedish version of the CARE-Q instrument, patients ranked as most important competent clinical know-how, while the nursing staff ranked expressive/affective behaviors as most important to make patients feel cared for. The results show significant differences (p less than 0.05) between the two groups in the rating of 29 of the instrument's 50 specific behaviors and in five out of six subscales combining individual items. Thus, patient perceptions of important nurse caring behaviors differ from staff perceptions. These results are similar to those from other studies of hospitalized patients' perceptions of caring. The staff's results are in accordance with studies of professional nurses' perceptions of caring. The findings support conclusions by other authors. PMID- 1938184 TI - The longitudinal effectiveness of osseointegrated dental implants. The Toronto Study: bone level changes. PMID- 1938185 TI - Functional preprosthetic orthodontics and prosthetic reconstruction with resin bonded fixed partial dentures. AB - When a resin-bonded fixed partial denture is planned in the maxillary anterior region, special attention must be paid to occlusal diagnosis. Specific instrumental diagnosis is necessary to define the functionally important factors: the anterior teeth, the occlusal plane, the temporomandibular joint, and their three-dimensional relation. The optimal treatment in an anterior-guided occlusion is a complete integration of the retainers in the given tooth form without altering the original inclination of the palatal guiding surfaces of the anterior teeth. In many cases, preprosthetic orthodontics is indicated because of functional and esthetic reasons. The objective is to achieve an anterior tooth position that allows the retainers of a resin-bonded fixed partial denture to be incorporated with the designed inclination of the guiding surfaces, using noninvasive preparation techniques. Preprosthetic orthodontic treatment planning, possible problems, and limiting factors as well as the subsequent prosthetic reconstruction have been described in detail. The interdisciplinary treatment has to be planned individually for each patient, depending on the functional diagnosis and the clinical and anatomic situation. PMID- 1938186 TI - Guided tissue regeneration procedure using a fibrin-fibronectin system in surgically induced recession in dogs. PMID- 1938187 TI - Topographical analysis of the facial areas most susceptible to infection with transmissible diseases in dentists. PMID- 1938188 TI - Screening for human immunodeficiency virus. AB - Screening for human immunodeficiency virus (HIV) antibodies as a means of preventing both the progress and spread of acquired immunodeficiency syndrome (AIDS) is problematic in terms of efficacy, effectiveness, and ethics. The few desired effects are mostly offset by greater and more certain undesirable effects on individuals and society. PMID- 1938189 TI - Assessment of screening for cancer. AB - Screening has a relevant role in and is likely to become an increasingly important instrument for cancer control in the near future. This overview summarizes some of the available evidence on the issue. Some of the opinions are well established. The apparent absence of consensus on other issues should be critically evaluated, too, because the evidence on some procedures is substantially more convincing than that on others. High costs, low compliance, poor curability, and substantial false positive rates, in a disease as relatively rare as cancer, often counterbalance in practice the theoretical benefits of diagnostic anticipation. In screening as well as in treatment for cancer, it is unlikely that major technical breakthroughs will occur in the near future. The evaluation of whether the benefits likely to be achieved by the screening program outweigh its disadvantages by a sufficient margin, therefore, should rely on large and carefully planned controlled studies. PMID- 1938190 TI - Assessing school health education programs. AB - This review focuses on the component of health education directed at achieving changes in health behavior. Much of the work in this field has centered on health behavior that has a role in preventing future disease. Because the evidence is strongest in relation to coronary heart disease (17), considerable effort has been devoted to this area. Walter et al. (34) indicated that the most relevant forms of health behavior to be considered in school-based programs on heart disease are those relating to diet, physical activity, and smoking. Programs relating to each of these behaviors are addressed here. PMID- 1938191 TI - Assessing technologies for preventing injuries in motor vehicle crashes. AB - Motor vehicle crashes are a leading cause of morbidity and mortality. In the Haddon matrix, crashes are divided into three phases and factors affecting each phase. In the context of this matrix, the effectiveness, use, and legislation of safety belts and airbags are discussed, using process, injury, and economic outcome measures. PMID- 1938192 TI - Assessing population-based programs to reduce blood cholesterol level and saturated fats. AB - This article reviews seven community-based programs for prevention of cardiovascular disease and their effects on blood cholesterol levels and saturated fat intake. In two programs, cholesterol levels were reduced more in the intervention area than in the reference area. In two other programs, cholesterol increased less in the intervention area than in the reference area. In one program, cholesterol levels initially fell in the intervention group and increased in the reference group; after the first 4 years, the levels also started to increase in the intervention group. The final two programs reduced cholesterol equally in both groups. Only two programs reported on the intake of saturated fats; in both, intake of saturated fat was reduced more in the intervention area than in the reference populations. In one program area, total intake of fat was reduced more than in the reference area. Published data do not allow us to draw conclusions regarding which components of the programs were most important. These studies show that the average blood cholesterol level can be affected in a general population. PMID- 1938193 TI - Oral disease prevention technologies for community use. AB - Dentistry is perhaps the most prevention oriented of the many disciplines in health care. This article examines technologies for the prevention of caries (including the use of fluoride, oral hygiene and prophylaxis, sealants, and dietary modifications), periodontal disease, and soft-tissue lesions that can be used in community-oriented programs. PMID- 1938194 TI - Assessing community interventions to reduce smoking. AB - Few major, community-based antismoking programs have undergone specific evaluation in developed countries; the number is even lower in developing countries. Yet not all evaluation need be elaborate, expensive, or overly time consuming. Data on tobacco trade, import and export, taxation, mortality, and morbidity may already exist within government departments and can be used for evaluation. Published information from the tobacco industry may be obtained easily in trade journals and annual reports. Universities and international and overseas national health agencies may offer information, assistance, and expertise. Indirect evaluation of the importance of any particular antismoking intervention can be measured by how strongly the tobacco industry opposes that measure. PMID- 1938195 TI - Evaluation of immunization policies for peacekeeping missions. AB - This article first examines data bases available to assess the risk of vaccine preventable diseases (VPD). In the second part, immunization recommendations and practices are briefly evaluated in view of the risk of exposure to VPD and of the efficacy and safety of available vaccines. PMID- 1938196 TI - Some observations on the assessment of preventive technologies. PMID- 1938197 TI - Estimating the effectiveness of perinatal care technologies by expert opinion. AB - The majority of technologies in use in perinatal care were organized into 45 technological functions. Forty-six experts from 19 different regions of Brazil and other Latin American countries then selected a "basic package" (BP) of 15 technological functions. Considering the 12 main causes of perinatal mortality in Brazil, the experts estimated the number of preventable deaths, assuming universal coverage by the BP and the additional reductions that could be obtained by gradually adding other technological functions to the BP. A simulation was performed for the 26 states of Brazil to identify regional priorities for the diffusion of technological functions. For most regions, the BP appears to be the most effective intervention, with the potential of reducing perinatal mortality by 33%, followed by "coordination of services and referral of pregnant women" (14%), and "treatment of respiratory conditions" (11.8%). PMID- 1938198 TI - Issues in cochlear prosthetics from an international survey of opinions. AB - Cochlear prostheses are beginning to be implanted regularly to restore hearing in profoundly deaf patients, but there is little agreement on the relative merits of the many different designs and rehabilitative procedures. We report on the responses to a technology assessment questionnaire that was sent to 120 researchers and clinicians worldwide who have been at the forefront of research in this field. PMID- 1938200 TI - Duodenoscopic sphincterotomy for common bile duct stones in patients with gallbladder in situ. AB - Duodenoscopic sphincterotomy (DS) is a well established treatment for common bile duct (CBD) stones in post-cholecystectomy patients, but not in patients with gallbladder in situ. The main argument against the procedure in the latter set of patients has been that by performing it, one is leaving behind the diseased gallbladder which may require further treatment. We have, however, performed 60 DS in 49 patients with gallbladder in situ. The clinical picture of these patients was characterized by abdominal pain in 79.6%, jaundice in 91.8%, history of cholangitis in 46.9%, severe acute cholangitis at the time of DS in 28.6% and a major associated illness in 10.2% of them. Adequate sphincterotomy was performed in 91.8% of the patients with successful stone extractions in 93.3% and an overall CBD clearance in 85.7%. One patient (2%) with severe acute cholangitis, who had presented in a moribund state, died despite adequate DS. Three patients (6%) experienced an exacerbation of acute cholangitis after DS, two of them requiring emergency surgery. During subsequent follow-up, elective cholecystectomy was performed in 26 (54%) patients. Five additional patients are awaiting surgery. Seventeen (36%) patients continue to have their gallbladders in situ and over a mean follow-up period of 12.8 months (range, 4-32 mos) they have remained asymptomatic except for brief episodes of biliary pain in 2 patients. It is concluded that DS relieves the symptoms of CBD stones even in patients with gallbladders in situ and may suffice for patients who are frail, elderly and who have major associated illnesses. PMID- 1938199 TI - Proximal gastric vagotomy. A comparative study between the standard technique and the extended technique associated with denervation of the greater curvature. AB - Forty-six patients in the postoperative period of proximal gastric vagotomy (PGV) for duodenal ulcer (DU) were studied comparatively to verify whether the dividing of the gastroepiploic nerves (Rosati's maneuver) can reduce or not the occurrence of recurrent ulcer as it was proposed. Twenty-one patients who underwent PGV associated with Rosati's maneuver (PGV-R) were compared to 25 after standard PGV (PGV-S), according to several criteria: (1) clinical evaluation; (2) pre and postoperative basal and pentagastrin-stimulated gastric acidity; (3) postoperative basal and pentagastrin-stimulated serum pepsinogen; (4) postoperative basal and sham feeding-stimulated serum gastrin; (5) postoperative endoscopy; (6) endoscopic Congo red test. Both groups were similar (P greater than 0.05) as to age, sex, levels of preoperative gastric acidity and had a 24.4 month average follow-up (12 to 58 months). There has been no significant difference between the techniques studied as to clinical, secretory, morphological or hormonal gastric tests, although PGV-R proved more effective in reducing basal gastric acidity than PGV-S (P less than 0.05). We concluded that Rosati's maneuver does not improve the results obtained with PGV, although it provided greater reduction of basal gastric acidity than PGV-S. PMID- 1938201 TI - Acute acalculous cholecystitis. AB - Thirty-two patients with acute acalculous cholecystitis are presented. The age of the patients ranged from 1 to 80 years, with an average of 46.3 years. Acute acalculous cholecystitis occurred during the postoperative period in only four patients. Three patients were receiving total parenteral nutrition and 16 patients had one or more associated medical diseases. One patient had acute acalculous cholecystitis due to mechanical obstruction of the cystic duct caused by a diaphragmatic hernia. The most frequent signs and symptoms were right upper quadrant abdominal pain, nausea, vomiting, fever, abdominal mass, and jaundice. All patients were subjected to cholecystectomy. Nine (28.1%) gallbladder specimens had gangrene. Pericholecystic perforation was observed in four patients (12.5%) free perforation in one patient (3.1%), and empyema of the gallbladder in one patient (3.1%). Bacteria were cultured from 18 of 24 bile specimens. E. coli was the most common organism isolated. The overall postoperative mortality and complication rates were 15.6% and 40.6% respectively. The average hospital stay was 16.4 days. PMID- 1938202 TI - Left lung allotransplantation in pig feasibility and transplanted lung function. Experimental Lung Transplant Group of Ospedale Maggiore of Milan. AB - Changing attitudes to animals in research and practical considerations prompted the authors to evaluate whether the pig might be a suitable substitute for dog and baboons for single left lung transplants. Twenty-nine paired pigs were used. The first transplants on 13 pairs (group 1) were done to adapt the lung transplant technique to pigs; later transplants on 16 pig pairs (group 2) were done to evaluate operative survival, and function and histological modifications of the transplanted lung in the absence of immunosuppressive treatment. Surgical and anesthetic techniques for both donor and recipient are described in detail. The survival rate in group 2 was 68%. Hemodynamic and blood gas changes were assessed during operation. PaO2 did not drop significantly after occluding the right pulmonary artery by an inflatable cuff placed around it; this suggests that the function of the transplanted lung was preserved. The pigs were put down on the third postoperative day. Vascular and bronchial anastomoses were patent and intact, but the transplanted lung was macroscopically and microscopically altered. Lung transplants can be performed in pigs and the transplanted lung seems to be capable of functioning immediately after the operation. Alteration in the lung after 3 days is probably due to rejection. PMID- 1938203 TI - Closure of abdominal wounds with continuous nonabsorbable sutures: experience in 1697 cases. AB - From September 1976 to September 1989, the author routinely used continuous nonabsorbable sutures for closing abdominal incisions in 1697 consecutive laparotomy patients, including 696 men and 1001 women. These cases did not involve any type of hernia repair. In addition to being quick and cost-efficient, the continuous technique allowed tension to be distributed evenly along the suture line. During a follow-up period of up to 13 years, six patients presented suture granulomas, and two had late incisional hernias (greater than six months postoperatively). No hematoma formation, infection, or suture-line disruption was encountered. The author concludes that continuous nonabsorbable sutures are preferable to interrupted nonabsorbable sutures for closing a wide range of abdominal incisions. PMID- 1938204 TI - Obstructing carcinoma of the left colon: treatment by extended right hemicolectomy. AB - Obstructing carcinoma of the left side of the colon causes proximal distension of the colon with subsequent thinning of the colonic wall and vascular impairment. Conventional surgical treatment is multi-staged. Each stage carries its own morbidity and mortality. An alternate treatment, extended right hemicolectomy, requires a single surgical procedure. Fifty-six cases of acute obstructing carcinoma of the left colon are presented: 16 in Group I were treated conventionally; 40 in Group II were treated by extended right hemicolectomy. In Group I, four died within one week of surgery. Six survived with a colostomy; all suffered from poor quality of life until death. For the six who received complete treatment, average total hospitalization was 54 days. Group II suffered no peri operative mortality. Patients were discharged without a colostomy after an average hospitalization of 15.7 days. Advantages of and conditions for treatment by extended right hemicolectomy are discussed. PMID- 1938205 TI - Intra-Peritoneal Chemo-Hyperthermia (CHIP): a new therapy in the treatment of the peritoneal seedings. Preliminary report. AB - After an experimental study in dogs, authors report a new therapeutic device for peritoneal seedings (Intra-Peritoneal Chemo-Hyperthermia) and their preliminary results in five patients. They observed no mortality and no morbidity with this protocol using Mitomycin as antimitotic and hyperthermia as sensibilisation agent. This new technique means important technological and time investment but preliminary results appear to be encouraging and authors intend to standardize the present apparatus in order to go on using this device and obtain more experience. PMID- 1938206 TI - Giant emphysematous bullae: surgical treatment using the median sternotomy approach. AB - Seven patients were operated for simultaneous excision of giant emphysematous bullae through a median sternotomy. They were all symptomatic and with a history of alcohol and/or drug abuse. Preoperative evaluation included bilateral chest tomograms and complete pulmonary function test. Surgical technique included bilateral resection of giant bullae and pleurodesis with minimal postoperative morbidity and no mortality. No correlation was found between symptomatic clinical improvement and measured postoperative pulmonary function. The median sternotomy approach is indeed the method of choice for bilateral giant emphysematous bullae. PMID- 1938207 TI - Ultrasonically guided pleural tap. AB - The ultrasonically guided pleural tap described here is technically easy even for a small amount of pleural effusion, and can be carried out even by junior doctors in training. We stress that ultrasound scanning should form part of the practical experience of general surgeons. PMID- 1938208 TI - Chronic venous insufficiency disease. Its etiology. A new technique for vein valve transplantation. AB - This is a two-year study of 25 patients with venous insufficiency who were found to be in the terminal stage, referred to in this paper as chronic venous insufficiency disease (CVID). Apart from the usual signs and symptoms of venous insufficiency, the patients were found to have severe pain on weight bearing, inability to ambulate, and nonhealing lower extremity ulcers as common features that did not respond to conservative management. The most common underlying etiology was valvular incompetency. In the surgical management of these patients, at present, all the procedures described in the literature are primarily performed in the femoral veins of the groin or above the knee. A new technique is described in this paper that enables one to transplant vein valve segments to distal popliteal vein below the knee. There was a six- to twenty-four-month follow-up. Patients were periodically followed up with venography, venous pressure measurements, and venous reflux studies. PMID- 1938209 TI - Ultrasonography and computed tomography in the diagnosis of portomesenteric vein thrombosis. AB - This study was undertaken to evaluate ultrasonography (US) and computed tomography (CT) in the diagnostics of portomesenteric vein thrombosis (PMT). Between 1972-1988 we found 40 cases with PMT, all verified in angiography and/or autopsy. Between 1972-79 US and CT were never used, when 19 cases with PMT were found (1 premortem diagnosis with splenoportography). Between 1980-88 there were 21 patients with PMT. US was performed in 13, detecting PMT in 2. CT was performed in 5 patients confirming US diagnosis in 2 cases and revealing one further PMT. One PMT was diagnosed in the venous phase of an arteriography. The sensitivities of US and CT to detect PMT were 15% (2/13) and 60% (3/5) (p less than 0.05). The delay until diagnosis decreased from 27 +/- 28 days in 1972-79 to 12 +/- 9 days in 1980-88 (p less than 0.02). However, neither the rate of correct antemortem diagnosis (5% vs 19%) nor the survivals (68% vs 65%, 95% vs 81%, 95% vs 100% at 1, 12 and 60 months) were improved. Because only the patients with correct diagnosis received appropriate therapy, followed by longest survivals, the importance of the diagnostic attempts should not be questioned. CT may be more sensitive than US for detecting PMT, but neither method have yet replaced angiographic techniques. PMID- 1938210 TI - Surgical treatment of hydatid cysts of the pancreas. AB - This series consists of seven patients with hydatid cysts of the pancreas; five females and two males, with an average age of 31 years. In a follow-up extending up to 33 years, about a 50% rate of correct preoperative diagnosis was recorded. The most sensitive and effective diagnostic modalities such as latex agglutination, ultrasonic, radionuclide, computerized tomographic and magnetic resonance imaging techniques were not available till the late seventies and therefore were only used during diagnosis of the latter 3 cases. Four patients had cysts located in the head of the pancreas. Three cysts were situated in the body and tail. Two distal pancreatectomies, two cystectomies and three marsupialization and external drainage procedures were performed for the surgical management of these cases. Two of the marsupialized and externally drained patients had fistulas which eventually dried up within a month leading to a total morbidity of 29% and a mortality rate of nil. PMID- 1938212 TI - Recurrent nerve palsy due to parathyroid cyst. AB - Cysts of the parathyroid gland are uncommon neck masses and difficult to diagnose. They can cause symptoms by endocrinological function or by pressure on surrounding structures. A case of recurrent nerve palsy due to a parathyroid cyst is presented. Aspiration of parathyroid cysts can be diagnostic and therapeutic in some cases. PMID- 1938211 TI - Ultra sound guided percutaneous cholecystostomy. AB - Ultrasound guided percutaneous cholecystostomy was performed in 11 patients. In 9 cases there was surgical jaundice due to obstruction of the common bile duct and in 2 cases it was done for empyema of the gall bladder. The placement of a catheter in the gall bladder was successful in all cases. In one case, due to obstruction of the cystic duct, biliary decompression was not achieved. Bile leak or haemorrhage did not occur in any patient. The technique and results are reported, the possible uses of this procedure are discussed and its potential use in providing access to the biliary tree is highlighted. PMID- 1938213 TI - Trochanteric fractures treated with the Pugh nail: a study of 270 cases. AB - We report a series of 270 intertrochanteric fractures of the femur which were treated with the Pugh nail in our department. We used it as a standard treatment of intertrochanteric fractures and lateral fractures of the femoral neck. The Pugh nail method is characterized by a simple technique, a low rate of complications, and early ambulation and weight-bearing, which is important for the mostly aged patients (average age: 81 years). 81% of the patients could be ambulized with weight-bearing within two weeks after operation. 79% of them were able to walk by themselves at discharge from hospital. The rate of complications was 17% without urinary infections. Mortality was 16%. Complications and mortality did not depend on the type of fracture but on the age of the patients and on concomitant diseases. PMID- 1938214 TI - Value of osteomedullography in the early diagnosis of non-union in tibial diaphyseal fractures. AB - Osteomedullography was performed in 17 diaphyseal fractures of the tibia at ten to 12 weeks from injury to assess the reliability and sensitivity of the procedure in predicting non-union. It was found to be accurate in more than 80% of cases in predicting the ultimate outcome early in the course of fracture healing. PMID- 1938215 TI - Metastatic renal cell carcinoma (RCC): spontaneous regression, long-term survival and late recurrence. AB - We report 4 cases of metastatic renal cell carcinoma (RCC) with long-term survival either following radical nephrectomy alone or in combination with radio- or hormonal therapy. Two patients with lymph node metastases showed a long-term survival of 12 or more years following radical tumour nephrectomy (with lymphadenectomy) and radiotherapy. One of them exhibited a histologically proven tumour recurrence nearly 12 years after primary surgical treatment and died shortly later; the other one is still without any evidence of metastatic disease. Two other patients exhibited spontaneous regression of pulmonary metastases: one regression occurred after radical tumour nephrectomy alone, the other one after successful primary hormonal treatment and subsequent radical tumour nephrectomy. The following important aspects are emphasized: 1. Renal cell carcinoma is a very unpredictable tumour. Once the diagnosis of renal cell carcinoma is proved, a patient can never be considered cured. 2. Although adjuvant palliative nephrectomy has produced contradictory results in several reports, radical tumour nephrectomy either alone or in combination with other adjuvant therapies such as radiotherapy, hormonal or immunological treatment, can be worthwhile. Cases with long-term survival and spontaneous regression of distant metastases are proof of this. Besides, if carefully selected, the mortality rate of different adjuvant therapies is not significantly higher in patients with metastatic disease than in patients without metastases. The world literature on this subject is reviewed. PMID- 1938216 TI - Teflon injection in the treatment of vesicoureteral reflux: a promising alternative for surgery. AB - Vesicoureteral reflux is a common disorder of the urinary tract in children. The incidence is especially high in patients suffering from urinary tract infection. There is controversy in the management of the disorder and a recently introduced method, Teflon injection, seems to offer a promising alternative as a non invasive technique. PMID- 1938217 TI - The fate of contralateral ureter after ipsilateral reimplantation in unilateral vesicoureteric reflux. AB - Four patients out of 23 girls and 7 boys who were treated by successful ureteroneocystostomies for unilateral reflux had postoperative contralateral reflux (13.33%). Three of these 4 refluxing ureters resolved with medical treatment. A second surgery was needed in only 1 case (3.33%) who did not respond to medical treatment. There was no correlation between the preoperative severity of ipsilateral reflux, intravenous urography findings and the onset of contralateral reflux after unilateral reimplantations. Data from this study and previous works indicated that bilateral reimplantations are not warranted for unilateral refluxing renal units unless there are position and shape anomalies at the ureterovesical angle and a very careful preoperative evaluation of the patients is mandatory in this regard. PMID- 1938219 TI - Relationship between the left spermatic vein diameter measured by ultrasound and palpated varicocele and Doppler ultrasound findings. AB - Fifty cases admitted to the urological clinics of Turkish State Railways Hospital, Ankara, were examined by scrotal ultrasonography in order to find the relationship between the left spermatic vein diameter measured by ultrasound and palpated varicocele and Doppler ultrasound findings. In the measured 5-6 mm spermatic vein diameters palpable varicocele and venous regurgitation were found in 100%, in the measured 3-4 mm diameters palpable varicocele was found in 50% and venous regurgitation in 64.5%, and in the measured 1-2 mm diameters palpable varicocele was found in 16% and venous regurgitation in 24%. PMID- 1938218 TI - Analysis of tissue ABH antigens in superficial bladder tumours. AB - The determination of ABH blood group antigens for the prognosis of superficial bladder tumours was evaluated. A total of 114 cases of superficial bladder tumours were studied, and all cases were treated by transurethral resection (TUR). The 5-year recurrence rate was 42%. The ABH antigenicity provided more useful information than the grade in predicting recurrence of the tumours. The period from the initial TUR till the first recurrence in antigen-negative tumours was 17.5 months, which was shorter, though not significantly, than the corresponding period in antigen-positive tumours of 25.2 months. In addition, the presence or absence of isoantigens of tumours having two or more recurrences was examined individually. PMID- 1938221 TI - Long-term prognosis of chronic glomerulonephritis. AB - The dependence of actuarial survival rates on morphological and clinical manifestation of chronic glomerulonephritis (CGN) has been studied in 520 patients followed up for 2-42 years. In grouping the patients along two signs- histological lesion and relapse incidence--the survival in different morphological forms of CGN was found to be similarly dependent on the illness activity. It was high in rare and the lowest in frequent and persisting relapses. Hypertension, high-grade tubulo-interstitial changes and sclerosis over 50 per cent of glomeruli indicate a poor prognosis as signs of severe renal damage under which each relapse may hasten the lethal outcome. Identification of the histological appearance is of high importance in CGN prognosis because of their different manifestations and tendency to relapse. PMID- 1938220 TI - Lipid metabolism in young males with hypotestosteronaemia and oligospermia prior to, during, and after treatment. AB - Relationships between plasma testosterone levels and selected parameters of lipid metabolism were studied in a group of young sterile males prior to, during, and after hormone therapy. Initial hypertriacylglycerolaemia and decreased concentrations of HDL cholesterol returned to normal values after 30 days of methyltestosterone administration. LDL cholesterol concentrations decreased significantly as did plasma apolipoprotein B levels. These changes persisted also one month after cessation of treatment. The results suggest that restoration of initially decreased testosterone levels in the studied group of sterile males is associated with the restoration of the lipid profile. PMID- 1938222 TI - Effect of heparin and prostacyclin-heparin infusion on blood coagulation in haemodialysed patients. AB - In 10 patients (8 men and 2 women) aged 28 to 58 years (mean 44.4 years) treated by repeated haemodialysis due to end-stage renal failure, the bleeding time, whole-blood coagulation time, one-stage prothrombin time, thrombin time of plasma, activated partial thromboplastin time (APTT), fibrinogen level and euglobulin lysis time have been determined (1) during a 4-hour haemodialysis using heparin as an antithrombotic agent, and (2) one week later in the course of another haemodialysis using prostacyclin-heparin. The values for any of the above parameters with both anticoagulant treatment types did not differ. Plasma fibrinogen level after haemodialysis was significantly lower after administration of heparin alone as compared with the group treated by prostacyclin-heparin infusion. During haemodialysis performed with prostacyclin-heparin infusion, activation of the blood fibrinolytic system was manifested by a significant shortening of euglobulin lysis time, observed after 1.5 hours and after the end of haemodialysis. The above phenomenon did not occur when haemodialysis was performed with heparin alone. PMID- 1938223 TI - Nonamyloidotic fibrillary glomerulopathy. Report of a case and review of the literature. AB - A 29-year-old man had oedema, proteinuria in nephrotic range, haematuria and cardiac arrhythmia (second grade atrioventricular block). The pathologic findings of kidney biopsy showed in light microscopy diffuse mesangial matrix increase with mild mesangial proliferation and variable thickening of the glomerular capillary walls. IgG, c3 and c1q were intensely fluorescent and exhibited a diffuse granular pattern in mesangial areas and along the capillary walls. Both kappa and lambda chains were weakly positive in the same pattern. Ultrastructurally, microfibrils of about 20 nm in width were seen to be deposited in mesangial areas and along the glomerular basement membranes. Congo red stain and metachromasia were negative. Neither cryoglobulinaemia nor paraproteinaemia including light chains were found. The aetiology of nonamyloidotic fibrillary glomerulopathy is unknown and no clear-cut clinical or pathologic pattern has emerged. It may represent more than one disease process with a common morphologic expression. PMID- 1938224 TI - Left renal haematuria by compression of an unusual vein. AB - A 55-year-old female had an episode of massive haematuria. An abnormal venous branch was under compression just before it joined a persisting left inferior vena cava. The main renal vein was not occluded and peri-ureteral varices had not been formed. Although it is a complicated anomaly which has not been reported, a variety of venous abnormalities might be responsible for unexplained renal haematuria. PMID- 1938225 TI - Relationship between metabolic acidosis and calcium phosphate urinary stone formation in women. AB - The relationship between the degree of metabolic acidosis and calcium phosphate stone formation was studied. Furthermore, the reasons why renal tubular acidosis (RTA) and primary hyperparathyroidism (PHPT) dominantly occur in women, and female stone formers more often produce calcium phosphate stone are discussed. Blood was slightly more acidotic in women than in men in both the urolithiasis and the control groups. Likewise, blood was significantly more acidotic and urinary pH significantly higher in patients with PHPT. Patients with RTA had severe metabolic acidosis, and urinary pH was highest among all groups. Calcium phosphate concentration was significantly higher in women than in men, and was also higher in patients with PHPT than in those with urolithiasis. All patients with RTA had pure calcium phosphate stones. The reasons why females are more acidotic and have more calcium phosphate in stones are suspected to be related to progesterone and urinary tract infection. PMID- 1938226 TI - Xanthine urolithiasis: ultrastructure analysis of renal and bladder calculi. AB - The surface structure of a xanthine stone from a patient with hereditary xanthinuria was examined using scanning electron microscopy. This revealed that the xanthine stone was composed of at least two very different structures. One was a spherical protrusion with craters and a fine granular surface and the other consisted of a granular growth of plate-like crystals. PMID- 1938227 TI - A case of quadruple carcinoma with special reference to ureteral cancer. AB - A case of quadruple carcinoma involving the ureter, stomach, transverse colon and rectum is described. All tumours have been removed and the patient is healthy without evidence of disease. PMID- 1938228 TI - The impact of squamous metaplasia in transitional cell carcinoma of the bladder. AB - The authors report a case of squamous cell carcinoma of the bladder induced by radiation therapy for transitional cell carcinoma, possibly from sites of squamous metaplasia, which were present at the time of initial diagnosis. Although data in the literature are not sufficient at the moment in terms of implication on prognosis, foci of squamous metaplasia during the initial diagnosis of transitional cell carcinoma must be carefully sought and their presence warrants caution in utilizing irradiation in the management of the disease. PMID- 1938229 TI - Carcinoma of the bladder in patients less than 40 years old. AB - Records of fifteen patients less than 40 years old with carcinoma of the bladder are reviewed. Fourteen patients with transitional cell carcinoma had well or moderately differentiated superficial papillary tumours. One patient with adenocarcinoma died within 4 months with progressive disease. Four patients experienced recurrences and 9 patients had no recurrence of tumour after a mean follow-up of 55 months. It is concluded that the fate of patients younger than 40 years with bladder cancer is not different from those in older age groups. PMID- 1938230 TI - Sacral agenesis with imperforate anus and its late complication: neuropathic bladder. AB - The authors report a rare case of imperforate anus as a congenital anomaly. Early diagnosis and close follow up are emphasized, in order to prevent the development of complications which may last for a lifetime. PMID- 1938231 TI - Hormonal treatment of symptomatic spinal cord compression in advanced prostatic cancer. AB - The authors describe 2 cases of symptomatic spinal cord compression due to metastatic prostatic cancer. Both cases showed marked improvement of cord compression after hormone therapy, and decompressive laminectomy was not necessary. The management of prostatic cancer patients with symptomatic spinal cord compression is discussed. PMID- 1938232 TI - Laser surgery in superficial penile tumours. AB - The first results of laser surgery in superficial penile tumours are reported. In 2 patients with condylomata acuminata, 2 cases of giant condylomata Buschke Lowenstein and in 2 patients suffering from early stage penile cancer diagnostic and/or therapeutic treatments using carbon dioxide or neodymium-YAG laser have been performed. In one patient with giant condyloma a recurrent tumour was found 5 weeks after the initial treatment and a second one using CO2 laser was done. All other patients are tumour-free with a follow up of 6-24 months and erectile function is normal. Therefore, in superficial penile tumours laser treatment is an excellent alternative therapeutic approach. PMID- 1938233 TI - Streptococcus agalactiae as a urinary tract pathogen in males and non-pregnant females. AB - The role of Streptococcus agalactiae (group B streptococci, GBS) was investigated for a period of one year in different clinical forms of urinary tract infection in males and non-pregnant females over 14 years of age. The pathogen has been isolated in quantities of greater than or equal to 10(5) cfu/ml in midstream voided urine from 32 patients with clinical signs of urinary tract infection and pathologic urinary sediment. In every group of B isolates the antibiotic sensitivity to antimicrobial agents was determined by the single disk method of Kirby-Bauer. GBS with the same characteristics were established in urethral specimens of 4 males as well as in the vagina and faeces of 11 females. As a rule, peroral treatment with ampicillin proceeded successfully. In addition, women with streptococcal vaginitis were treated topically with 2% solution of chlorhexidine. Our results have demonstrated that GBS might cause urinary tract infection, but the evaluation of GBS isolated in urine specimens is complex. PMID- 1938234 TI - Deoxyribonuclease activity in lymphocytes of patients with chronic renal failure treated conservatively. AB - The activity of nucleases and concentrations of highly important metal ions in T and B lymphocytes were examined. The source of lymphocyte was the blood of patients with chronic renal failure and activity of enzyme as well as ion concentrations were compared to the control group. Concomitant with the increase in enzyme activity was an increase of metal ion concentrations assayed in both T and B lymphocytes isolated from patients with renal disease. The data suggest that the enhancement of nuclease activity is a result of increased enzyme polypeptide synthesis and its stimulation by metal ions. Utilization of the nuclease test for monitoring uraemic toxicity is considered. PMID- 1938235 TI - High doses of furosemide in children with acute renal failure. A preliminary retrospective study. AB - The diuretic effect of high doses of furosemide alone and furosemide plus mannitol was analysed retrospectively in 30 children with acute renal failure. In 10 children (Group 1) renal failure developed mainly during glomerulonephritis, and in 20 children (Group 2) the cause was gastroenteritis. The diuretic effects of furosemide and furosemide plus mannitol were evaluated measuring the 24-hour urine volume at the time of anuria, oliguria or normal diuresis. The highest mean single intravenous doses of furosemide were 6.5 and 14 mg/kg in Groups 1 and 2, respectively; the highest average daily doses were 10.1 and 25.5 mg/kg, respectively. A broad relationship was observed between single i.v. dose and diuretic response following administration of furosemide (1.2 to 30.8 mg/kg). In both groups of patients a statistically significant negative linear correlation was found between the daily intravenous dose of furosemide and the 24-hour urine volume. Calculations based on the obtained regression equations showed that the expected 24-hour urine volumes corresponding to daily diuresis normal for age could be obtained after administration of daily 2.8 to 1.4 mg/kg furosemide in Group 1 and 9.3 to 2.3 in Group 2. It is therefore suggested that the total daily dose of furosemide should not exceed 100 mg in children with acute renal failure. Administration of furosemide plus mannitol did not result in higher daily diuresis as compared to 24-hour urine volume obtained when furosemide was given alone. Furosemide was well tolerated. Electrolyte disturbances, especially in Group 2, were the most frequent side effects due to high doses of furosemide. PMID- 1938236 TI - Indications for renal biopsy in patients with renal failure based on ultrasound investigations. AB - Forty-seven patients including 18 with renal failure were studied. Kidney length, degree of cortical echogenicity, parenchymal thickness, visibility and dimensions of renal papillae, and existence of renal cysts were recorded during abdominal ultrasound investigations in all patients. Indications and contraindications for renal biopsy were determined. Ultrasound is a valuable method of easy evaluation of indications for renal biopsy in patients with renal failure. This method avoids the risks of postbiopsy complications, drug overdosage as well as additional X-ray exposures and scintigrams. PMID- 1938238 TI - Vanadium transfer during haemodialysis. AB - The authors examined transport of vanadium (V) in 100 chronic haemodialysis (HD) patients. Serum V levels were different at the inflow and the outflow site. Vanadium was transferred from blood to dialysate through the membrane. Serum V levels decreased in the course of haemodialysis. PMID- 1938237 TI - Serum vitamin A, retinyl esters and vitamin E in nephrotic syndrome. AB - Serum vitamin A, retinyl esters and vitamin E were increased in a group of 33 patients with chronic glomerulonephritis and nephrotic syndrome without reduction of mean glomerular filtration rate. Despite hypoproteinaemia and reduced values of serum proteins with a different molecular weight, increased values of vitamin A protein carriers were found. Serum total cholesterol, LDL cholesterol, triglyceride, prebeta und beta lipoproteins were increased, HDL cholesterol was within the reference range. Direct relationships were found between serum retinyl esters and vitamin A, and between serum retinyl esters and prealbumin. Indirect relationships were detected between serum total cholesterol and total proteins, serum total cholesterol and albumin, and serum vitamin E and albumin. The increased values of vitamin A, retinyl esters as well as its protein carriers and of vitamin E were probably a manifestation of enhanced protein and lipid synthesis in the liver as a result of albumin depletion. These results show true A and E hypervitaminosis in patients with nephrotic syndrome. PMID- 1938240 TI - Multiloculated renal cell carcinoma. AB - Multiloculated renal cell carcinoma and multilocular renal cyst with renal cell carcinoma are uncommon diseases. We report on 2 cases of multiloculated renal cell carcinoma. To our knowledge 16 cases of multiloculated renal cell carcinoma and multilocular renal cyst with renal cell carcinoma have been previously described in detail. The authors review the literature and discuss the aetiology and diagnosis of the disease. PMID- 1938239 TI - Epidemiology of urolithiasis in the elderly. AB - To estimate the epidemiology of upper urinary stones in the elderly, a total of 1,957 patients (1,349 men and 608 women) with urolithiasis were studied. The ratio of men to women was approximately 3:1 in middle-aged (between 30 and 59 years), 1:1 in young (29 or younger) and 1:1 in old patients (60 or older). Compared with the age distribution of the entire Japanese population, the incidence of urinary stones was very low in both male and female children, twice as high in middle-aged men, slightly higher in middle-aged women, and equal or slightly lower in the male and female elderly. Stones of calcium oxalate and uric acid occurred more frequently and those of calcium phosphate and struvite less frequently in men than in women. This tendency was especially obvious in the middle-aged. In the old generation, calcium oxalate stones occurred almost equally in men and women. Results of urinary stone analysis were similar among men of the three generations, although the incidence of uric acid stones increased with patient age. In women, however, the incidence of calcium oxalate was higher in the young and old generations, while that of calcium phosphate was higher in the middle-aged. PMID- 1938241 TI - Chronic adult renal vein thrombosis: two unusual cases and a review of the literature. AB - A panorama of signs and symptoms from the primary and associated disease processes complicates the clinical picture of chronic adult renal vein thrombosis (RVT). This has made the diagnosis of RVT very challenging. In addition, this entity is often overlooked in differential diagnosis due to the patient's often multiple other problems. Detecting this condition may lead to restoration of renal function compromised by renal vein obstruction and thus be of critical benefit in patients who often have compromise of renal function. Two unusual presentations of chronic RVT are discussed and provide a basis for review of the salient features of aetiology, diagnosis and disease management, providing what is hoped to be useful suggestions in diagnosis and management of this condition. PMID- 1938242 TI - Screening of asymptomatic siblings of patients with vesicoureteral reflux. AB - Familial trait in vesicoureteral reflux (VUR) has been revealed in many studies. This paper reports on 36 siblings of 25 patients operated for vesicoureteral reflux at our Department. Siblings aged 2 to 21 years were evaluated by urine examination, urine culture and voiding cystourethrogram (VCU) for VUR. All of the siblings were asymptomatic and VUR was found in only 4 of them (11%), unilateral in 3 cases and bilateral in one case. It is concluded that evaluation of siblings for VUR will be suitable for revealing the presence of urinary infection, and assessing them by VCU at the time they are first seen. PMID- 1938243 TI - Local BCG therapy of superficial bladder tumours. AB - A total of 126 patients, whose superficial bladder tumours (Ta-Tl) had been removed by TUR, were subjected to local BCG therapy. Marked by frequent though mild side effects, they presented a significantly lower rate of tumour recurrence than the control group under exclusive TUR treatment. During a follow-up period of 3 years, 74% of the patients proved recurrence-free. BCG and Adriamycin were found largely similar in degree of effectiveness. PMID- 1938245 TI - Endovascular electric surgery of varicocele. PMID- 1938244 TI - Histologic grading of prostatic adenocarcinoma: intraobserver reproducibility of the Mostofi, Gleason and Bocking grading systems. AB - Intraobserver variation of three grading systems--Mostofi, Gleason and Bocking- is examined. No significant difference was noted between the histological grades found in the two examinations by any of the three methods used. Neither the type of surgical procedure nor the number of slices with tumour influenced the reproducibility of histological grading within each system studied. In the Gleason system the intraobserver highest disagreement would not have resulted in change of therapy choice, but in 2% of tumours graded according to the Mostofi system this would have occurred if the choice of therapy would depend on the grading results. PMID- 1938247 TI - Sepsis caused by periurethral abscess. AB - The author presents an unusual case of general sepsis of the organism caused by periurethral abscess in a 38 years old man. The aetiology is discussed. PMID- 1938246 TI - Hydatid cyst of the seminal vesicle. AB - Hydatid disease has a high incidence in our country and causes significant complications. The authors present a case of unusual localization of hydatidosis, hydatid cyst of the seminal vesicle, and a review of the literature. PMID- 1938249 TI - True hermaphroditism: pre- and postoperative evaluation of gonadal function and the necessity of endoscopic examination for the search of cervix uteri at an early stage of diagnosis. AB - Three previously unreported cases of true hermaphroditism are described and discussed with regard to their gonadal function and the value of endoscopic examination. All three patients showed a good response of serum testosterone to stimulation with human chorionic gonadotropin before gonadal biopsy. The third patient showed significant elevation of serum oestradiol level on stimulation with human menopausal gonadotropin at two years of age before operation. Endoscopic examination to search for cervix uteri at an early stage of diagnosis, and pre- and postoperative functional evaluation of the gonads by hormonal stimulation are emphasized. PMID- 1938248 TI - Correlation between intracavernous papaverine injection, Doppler analysis and cavernosography in impotent patients. AB - Forty-four patients with impotence were evaluated by intracavernous papaverine injection, penile brachial index (PBI) determination and dynamic cavernosography. The correlation between these diagnostic procedures and their diagnostic value were investigated. It was concluded that the papaverine test is an efficient diagnostic procedure and can be used as the first step for the routine work-up of impotent patients. PMID- 1938250 TI - Heme biosynthesis and porphyrin studies in chronic renal failure patients following kidney transplantation. AB - El-Far and Sobh were the first to describe abnormalities in porphyrin metabolism in Egyptian patients with chronic renal failure (CRF). Our results were confirmed by others. The present investigation aims to study and discuss the nature of those abnormalities and changes in porphyrin metabolism in CRF patients following kidney transplantation. Blood samples and urine were collected from patients (with and without polycythaemia) as well as from normal controls. The activity of heme enzymes such as ALA-S, ALA-D, URO-S, PBGase and URO-D were assayed. Total blood porphyrins as well as enzyme activities such as ALA-S and URO-S were found to be highly significantly increased in all patients, while URO-D activity remained within normal range. The observed elevated erythrocyte porphyrins may be mainly due to increased activity of ALA-S, the rate-limiting enzyme in heme synthesis. The present study is the first of its kind which clearly demonstrates that successful kidney transplantation does not correct or rectify the abnormalities in porphyrin metabolism. PMID- 1938252 TI - Chemiluminescence of neutrophils in patients with glomerulonephritis treated with methylprednisolone. AB - The effect of high dose methylprednisolone (Solu-Medrol, Up John) (1000 mg) on chemiluminescence (CL) of peripheral blood neutrophils in patients with various primary glomerulopathies was determined. Contrary to the well-established influence of corticosteroids on in vitro suppression of leukocytic chemiluminescence, our studies disclose a remarkable enhancement of neutrophil chemiluminescent activity in patients receiving pulse methylprednisolone infusion. Subsequent administrations of the drug did not result in any significant change of the analysed parameters. Increased chemiluminescence returned to the pretreatment values within approximately seven days. A possible explanation for the observed phenomenon is discussed. PMID- 1938251 TI - Rhabdomyolysis and myoglobinuria associated with violent exercise and alcohol abuse: report of two cases. AB - Two cases of acute rhabdomyolysis with myoglobinuria and high levels of serum enzyme are presented. The first patient developed acute renal insufficiency in the context of a binge and heavy alcohol drinking lasting several days. He was treated with haemodialysis for three weeks, and survived. The second patient developed rhabdomyolysis and heavy myoglobinuria after playing squash vigorously. Forced mannitol-alkaline diuresis therapy for prophylaxis against hyperkalaemia and metabolic acidosis was performed. He did not develop renal failure. The clinical features, pathology and treatment of rhabdomyolysis and myoglobinuria are summarized. PMID- 1938253 TI - [Cough]. PMID- 1938254 TI - [Chronobiology]. PMID- 1938255 TI - [Chronobiology and sleep]. PMID- 1938256 TI - [Chronobiologic phenomena in endocrinology]. PMID- 1938257 TI - [Chronobiologic phenomena in gastroenterology]. PMID- 1938259 TI - [Disorders of circadian blood pressure changes]. PMID- 1938258 TI - [Nocturnal asthma and its mechanisms]. PMID- 1938260 TI - [Chronobiology of coronary heart disease. Current aspects of circadian rhythm and chronotherapy of myocardial ischemia]. PMID- 1938261 TI - [Comment on the contribution by H. Lollgen, W. Kottmann and U. Fahrenkrog: "Syncope"]. PMID- 1938262 TI - [Acute myocardial infarct (pathophysiology, diagnosis, therapy)]. PMID- 1938263 TI - [Quality of life and aging]. PMID- 1938264 TI - [Clinical aspects of hemorheology in the aged]. PMID- 1938265 TI - [Dementia--examination methods and possibilities for treatment in global acquired cerebral performance disorder]. PMID- 1938266 TI - [Multimorbidity and pharmacotherapy in the elderly]. PMID- 1938267 TI - [Therapy with psychotropic drugs in the elderly]. PMID- 1938269 TI - [Therapy with cytostatic drugs in the elderly]. PMID- 1938268 TI - [Peculiarities of cardiac glycoside therapy in the aged]. PMID- 1938270 TI - [Intensive care medicine in geriatrics--an assessment of current status]. PMID- 1938272 TI - [Intestinal angiodysplasia and risk of hemorrhage]. PMID- 1938271 TI - [Sudden increase in abdominal circumference in a young man]. PMID- 1938273 TI - [Coronary heart disease--modern concepts for the 90's. New approaches--modes of atherogenesis]. PMID- 1938274 TI - Role of laminin-binding integrin in the invasion of basement membrane matrices by fibrosarcoma cells. AB - Laminin is a large glycoprotein that is found in basement membranes and promotes cell adhesion and migration. In human fibrosarcoma cells we detected the presence of an integrin complex, with a Mr of 140,000/120,000 under nonreducing conditions, that bound specifically to laminin-Sepharose columns. Immunoprecipitation with monoclonal antibodies characterized this complex as alpha 6 beta 1. Attachment of the fibrosarcoma cells to laminin substrates was completely inhibited in the presence of anti-alpha 6 beta 1 antibody, while attachment to fibronectin and type IV collagen was unaffected. When seeded onto reconstituted basement membrane, the fibrosarcoma cells spread out, migrated, and invaded the matrix. In the presence of anti-beta 1 or anti-alpha 6 beta 1 antibodies, initial invasion through the matrix was inhibited. The results indicate that the HT1080 cells express the alpha 6 beta 1 complex and that it mediates their attachment to laminin. Furthermore, this receptor appears to be important during initial attachment and subsequent invasion of basement membrane like matrices. PMID- 1938275 TI - Junctional communication of highly and weakly metastatic variant clones from a rat mammary carcinoma in primary and metastatic sites. AB - We have investigated junctional intercellular communication (JC) in primary and metastatic sites, using two highly and two weakly metastatic variant clones which had been isolated from a rat mammary carcinoma cell line, c-SST-2. After each variant had been subcutaneously inoculated into syngeneic rats, tumor cells were isolated from local tumor (primary tumor) and their metastatic foci (lung, heart and kidney). The cells were then recultured, and we measured their JC in vitro by the dye transfer method with the fluorescent dye Lucifer yellow CH, and found that the homologous (tumor cell-tumor cell) JC of highly metastatic clones were less in recultured tumor cells from primary tumors than that of weakly metastatic clones. At the same time, the heterologous (tumor cell-normal fibroblast) JC of highly metastatic clones was less than that shown by weakly metastatic clones. On the other hand, tumor cells obtained from metastatic foci showed relatively reduced JC (homologous and heterologous) when compared with those from their primary tumors in the weakly metastatic clones. These data suggest that a decrease in and/or a loss of JC may play a role in the expression of metastatic properties. PMID- 1938276 TI - Heparin-binding sites of rat rhabdomyosarcoma cells with low and high metastatic capacity. AB - Proteins able to bind the iduronate containing glycosaminoglycans: heparin, heparan sulfate and dermatan sulfate, were detected in strongly (RMS 0) and weakly (RMS 8) metastatic rat rhabdomyosarcoma cell lines. The 35S-methionine labeled proteins solubilized from the cell membranes were chromatographed on Heparin-Ultrogel affinity column. The main retained protein migrated with an apparent molecular size of 19 kDa on polyacrylamide gel electrophoresis from both cell lines. The 19 kDa protein exhibited a higher affinity for iduronate containing glycosaminoglycans than for the glucuronate containing chondroitin sulfates. It was immunologically distinct from acid and basic fibroblast growth factors. The membranes of the RMS 8 cells contained about a two times higher amount of labeled 19 kDa protein than the membranes of the RMS 0 cells. The decreased amount of the labeled heparin-binding proteins in the highly metastatic cell line is in agreement with the previously evidenced decreased receptor mediated binding of the iduronate containing glycosaminoglycans by these cells. PMID- 1938277 TI - The development of a treatment model for lymph node metastasis in nude mice transplanted with rat fibrosarcoma clone A. AB - We have tried to establish a model for lymph node metastasis in nude mice transplanted with clone A of methylcholanthrene-induced rat fibrosarcoma. Tumor cells transplanted either subcutaneously or intrafootpad metastasized exclusively to the lymph nodes in nude mice treated with antiasialo GM1 antiserum. In the experiments of intrafootpad transplantation, all the mice died of disseminated lymph node metastasis if the leg was not resected, or was resected more than 3 weeks after the transplantation of clone A. Some mice whose legs were amputated 1 or 2 weeks after transplantation could be cured by amputation alone. The maximum effective dose of in vitro active drug could improve the survival in mice, and 3/5, 4/5, and 3/5 mice treated with MMC, ACNU and CDDP respectively were cured even if their legs were amputated 3 weeks after transplantation. This tumor bearing animal system was considered to provide a valuable experimental model for lymph node metastasis. PMID- 1938278 TI - Ocular toxicity of low-molecular-weight components of silicone and fluorosilicone oils. AB - Silicone oil (SiO) and fluorosilicone oil (FSiO) are injected into the vitreous cavity in difficult cases of retinal detachment surgery. SiO and FSiO contain linear and cyclic low-molecular-weight components (LMWC) that are thought to cause ocular toxicity. Using the purified oils (without LMWC) and some of the individual LMWC, the authors evaluated the relation of the LMWC to the short-term ocular toxicity of the oils. When octamethylcyclotetrasiloxane or other single small species of linear and cyclic LMWC of SiO were injected into the rabbit anterior chamber, severe inflammation and corneal edema were induced. The ocular responses to the single species of the LMWC of SiO decreased with an increase of the molecular weights. Cyclic LMWC of FSiO (a mixture of trimethyl-3,3,3 trifluoropropylcyclotrisiloxane and tetramethyl-3,3,3 trifluoropropylcyclotetrasiloxane) also induced inflammation and corneal edema. However, unpurified SiO and FSiO, as well as purified oils (via solvent fractionation), did not cause significant adverse ocular response, presumably because the amounts of LMWC (especially the smallest species) in the oils were relatively small. Using gas chromatography, the authors analyzed SiO and FSiO recovered from rabbit and human vitreous cavities up to 2 yr after injection. In most of the cases, the concentrations of LMWC in SiO decreased after injection. This is consistent with the possibility that LMWC diffused from the oils into the ocular tissues. The long-term effect of LMWC in intraocular SiO and FSiO has not been determined. However, diffusion of LMWC into ocular tissues may relate to the chronic ocular toxicity of the oils. PMID- 1938279 TI - The effect of caffeine on the human macular circulation. AB - The acute effect of caffeine on the retinal circulation was studied in 14 healthy volunteers using the blue field simulation technique, which provides measurements of the velocity of leukocytes flowing within the macular capillaries. Subjects adjusted the mean velocity (Vm) of computer-simulated leukocytes moving on a cathode ray tube screen to match that of their own entoptically perceived leukocytes before and 1 hr after a double-masked, randomized administration of 200 mg caffeine or placebo. Caffeine produced an average 13% +/- 5% (SEM) decrease in Vm (P less than 0.05) and a 9% +/- 3% increase in diastolic blood pressure (P less than 0.05). The decrease in Vm and, presumably, blood flow occurring despite the increased diastolic blood pressure probably is attributable to retinal vasoconstriction. This effect may result from caffeine's known inhibitory effect on adenosine, a potent vasodilator of the retinal vasculature. PMID- 1938280 TI - Cobalt increases photoreceptor-dependent responses of the chick retinal pigment epithelium. AB - While using cobalt (Co2+) to block synaptic transmission in an in vitro preparation of chick retina, the authors observed significant changes in the DC electroretinogram (DC ERG). Cobalt (3.0 mM) increased the amplitudes of all three photoreceptor-dependent responses of the retinal pigment epithelium (RPE): the c wave, fast-oscillation trough, and light peak. Intracellular recordings from RPE cells revealed that Co2+ increased those light-evoked changes in RPE membrane potentials that contribute to each of these responses. Monitoring of subretinal [K+]o with K(+)-selective microelectrodes showed that Co2+ increased the amplitude of the light-evoked [K+]o decrease, and this must contribute to the observed increase in c-wave and fast-oscillation trough because both are generated by this [K+]o change. Cobalt also increased the initial rate of [K+]o decrease at light-onset, the rate of subretinal [K+]o reaccumulation during maintained illumination, and the amplitude of the [K+]o overshoot at light offset. The Co(2+)-induced increases in light-evoked RPE responses and subretinal [K+]o changes may arise from a direct effect on photoreceptors because (1) blockade of postphotoreceptoral activity did not block these effects of Co2+; and (2) Co2+ did not alter significantly the electrical properties of isolated RPE choroid tissues. The authors conclude that, in the cone-dominated chick retina, Co2+ may act directly on the photoreceptors to increase the light response. PMID- 1938281 TI - The effects of Depo-Medrol preservative on the rabbit visual system. AB - Periocular injections of corticosteroids play an important role in the management of various ophthalmologic diseases. The Depo-Medrol vehicle, injected into the vitreous, was shown to be toxic to the lens and to the retina when applied at double strength. The authors examined the effects of Depo-Medrol and one of the components of its vehicle, myristyl-gamma-picolinium chloride (MGP), on the functional integrity of the rabbit visual system. Visual function was assessed objectively from the electroretinogram (ERG) and the visual evoked potential (VEP). The experimental drugs were injected into the vitreous humor of one eye while saline was injected into the fellow eye for control. Depo-Medrol did not produce any measurable effects on the ERG or the VEP. When MGP solutions were injected in concentrations at least twice as large as that in the Depo-Medrol, significant reductions in the light- and dark-adapted ERG responses were seen. The effects of the drug on the ERG responses was seen as early as 3 days postinjection and developed to its maximal level within 1-2 weeks. No ERG recovery was seen over a period of more than 2 months. The VEP, elicited by applying light stimuli to the experimental eye, was characterized by low amplitude and delayed implicit time compared with the response obtained from the control eye. PMID- 1938282 TI - Neuraminidase activity in acanthamoeba species trophozoites and cysts. AB - Acanthamoeba species, a widely distributed group of free-living amoeba, can infect humans and spread hematogenously after direct interaction with the mucosal surfaces. The mechanism underlying Acanthamoeba damage to the target cell is unknown. The authors report that trophozoites and cysts of Acanthamoeba species exhibit a neuraminidase activity that is membrane associated and released into the culture medium at the start of the logarithmic phase of growth. The enzyme activity is optimal at pH 5 and at 25-30 degrees C. Live parasites release sialic acid from human cells. Therefore, the neuraminidase of Acanthamoeba species could be relevant in the colonization and damage of the sialic acid-rich corneal epithelium and in the alterations of glycolipids associated with meningoencephalitis. PMID- 1938284 TI - Binocular beat VEPs: losses of cortical binocularity in monkeys reared with abnormal visual experience. AB - Binocular beat VEPs were recorded from anesthetized macaque monkeys with diverse visual rearing histories, including surgically induced esotropia, optical prism dissociation, optical anisometropia, monocular form deprivation (MD), and normal rearing. Dichoptic visual stimulation was produced by temporally modulating the luminances of uniform fields presented to each eye. Five pairs of temporal frequencies were used, all of which had interocular differences of 2 Hz. While normally reared animals exhibited robust binocular beat responses strongly tuned to temporal frequency, the responses from monkeys with abnormal rearing experiences showed losses in beat signal-to-noise ratios that correlated with the age of onset or duration of the abnormal visual experience. Surgical esotropia induced early in life (2 months of age) produced a virtually complete loss of the binocular beat response; the cortical losses were less severe as the age of surgery rose to 10 months. Monkeys reared with either anisometropia or optical dissociation also manifested substantial reductions in evoked beat nonlinearity. MD monkeys sutured relatively late in development (8 and 25 months) showed mild reductions. The correspondence of these results to earlier psychophysical data obtained from these animals, and the similarity of these results to previous findings with binocularly normal and abnormal humans, supports the use of the binocular beat as an objective, noninvasive index of binocular neural integrity. PMID- 1938283 TI - Variability of high-pass resolution perimetry in normals and patients with idiopathic intracranial hypertension. AB - High-pass resolution perimetry, or the "ring test," is a recently developed type of acuity perimetry. To determine its test-retest variability, we studied 10 normals and 10 patients with idiopathic intracranial hypertension (IIH) by testing both eyes four separate times. There was no increase in variability from the center out to 21 degrees of visual field eccentricity. However, there was a significant increase from 22 degrees to 29 degrees in both normals and IIH patients. Unlike light sensitivity threshold automated perimetry, with an increase in threshold level there was no significant increase in variability in either normals or patients. This may be because of the test's method, which thresholds by target size rather than intensity. As expected, there was a large intersubject variability in the patients, with the visual fields being significantly disturbed by analysis of total field, quadrants, concentric rings, and anatomic nerve fiber bundle regions. Surprisingly, there was no significant difference in the total within subject variability of normals and patients. Because with the ring test there is no increase in variability with an increase in threshold, this method of perimetry may have great utility for following patients with disturbed visual fields. The ring test appears to have advantages that promote low test-retest variability. PMID- 1938285 TI - Intermittent oscillopsia in a case of congenital nystagmus. Dependence upon waveform. AB - Spontaneous reports of oscillopsia are rare in cases of congenital nystagmus (CN). We examined the relationship between nystagmus waveform characteristics and oscillopsia in one such case. To reduce the patient's nystagmus, she was fitted with contact lenses. We examined the effects of tactile feedback by applying local anesthetic while she wore the lenses. When she was without lenses, we provided tactile feedback by applying gentle finger pressure to one eyelid. She was also asked to look at a peripheral afterimage. Nystagmus was analyzed for frequency, amplitude, foveation duration, and drift velocity, if foveation was not perfectly stable. Perceived target stability was recorded. The patient noted oscillopsia during the initial baseline recording and with lid pressure. The image was stable with contact lenses with and without anesthesia and during the second session baseline; at these times, drift velocity was less than 4 degrees/sec and foveation duration was greater than 100 msec. No oscillopsia of the afterimage in dark was noted; she perceived it moving with her gaze as she attempted to look at it. It appears that in some CN patients, the suppression of oscillopsia operates only within fixed limits of foveation stability and duration. When, because of internal or external factors, their nystagmus exceeds these, oscillopsia results. PMID- 1938286 TI - Magnetic resonance imaging of the rabbit eye. Improved anatomical detail using magnetization transfer contrast. AB - Proton nuclear magnetic resonance (NMR) imaging previously has been used to examine structure and pathologies of the eye. The present study investigates the use of a saturation-transfer technique, which exploits water-macromolecular proton magnetic interactions, to enhance image contrast in the rabbit eye in vivo. Upon steady-state saturation of the macromolecular-proton magnetization, the water-proton signal intensity will decrease in proportion to the degree of water-macromolecular proton magnetic interaction. NMR images of the eye collected using saturation transfer are shown to have superior contrast compared to conventional NMR imaging techniques, in regard to numerous ocular structures, including the iris, ciliary bodies, muscle, lens, and cornea. PMID- 1938287 TI - Searching for lung nodules. The guidance of visual scanning. AB - Four subjects searched a chest image for lung nodules using an eye position dependent display that presented the image of a nodule selectively to either the central or peripheral visual field, while preserving the appearance of the chest. The time required to scan the image and fixate the nodule was shortest for nodules that were both reported and accessible to the peripheral vision. A stepwise concentric reduction in the size of the peripheral field that could access the nodules only affected search performance when the field was less than 5 degrees. (A chest image subtends about 25 degrees.) These data support the hypothesis that the optimal scanning strategy for lung nodules consists of spacing fixation clusters 5 degrees apart, and that peripheral vision only acts as an adjunct in guiding the gaze to inconspicuous nodules. PMID- 1938288 TI - The impact of acoustic velocity variations on target detectability in ultrasonic images of the breast. AB - Experimentally obtained ultrasonic phase aberration profiles in the breast were used to investigate the impact of acoustic velocity variations on images of simulated breast lesions. The imaging properties of several phased-array transducers with varying frequencies and geometries were studied as phase error profiles of increasing magnitude were introduced. The targets studied were anechoic lesions of various sizes. The results indicate that phase aberrations significantly degrade the contrast of ultrasonic breast images, especially for high-resolution scanning systems. PMID- 1938289 TI - Use of perfluorooctylbromide (PFOB) to detect liver abscesses with computed tomography. Safety and efficacy. AB - Although perfluorooctylbromide (PFOB) is known to stimulate macrophages, particulates given intravenously (IV) can inhibit the body's response to infection by blocking the reticuloendothelial system. Since PFOB enhances abscesses on computed tomography (CT), the authors evaluated its safety and efficacy by assessing the mortality and abscess volume in 104 rabbits with intrahepatic abscesses given either PFOB or lactated Ringer's (LR), and by comparing its efficacy to that of 76% meglumine sodium diatrizoate (MSD76). Abscesses were produced by injecting a virulent strain of E. coli into the liver. Two days later, five of the rabbits had died. Of the remaining rabbits, 50 were given 5 g/kg PFOB IV, and 49 were given an equal volume of LR. All rabbits had a CT scan at four and at ten days after infusion. They were killed before the second CT scan. Thirty seconds before being killed, 28 rabbits given LR were given a bolus of 2 ml/kg MSD76 IV. Following CT, rabbits were frozen, sliced, and photographed. Abscess volumes were calculated by digitizing the photographs of the anatomic sections and the CT images. MSD76 enhanced the liver by 105 Hounsfield units (HU) more than the liquefied abscess center. The abscess wall enhanced to the same degree as liver, resulting in nonvisualization of three of six abscesses less than 3 mm in size, and a 30% underestimation of true abscess volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938290 TI - Sclerotherapy of the gallbladder in pigs. Development of a balloon catheter for a single-step procedure. AB - Gallbladder sclerotherapy after permanent cystic duct occlusion, to prevent gallstone recurrence in nonsurgical gallstone therapy, is at least a two-stage procedure. A balloon catheter was developed to perform gallbladder sclerotherapy with only temporary occlusion of the cystic duct, and the efficacy and safety of this method was subsequently investigated. Twenty pigs underwent cholecystostomy for positioning of a 7-Fr triple-lumen balloon catheter with proximal side holes. Sclerotherapy with 96% ethanol and 3% sodium tetradecyl sulfate for 20 minutes was performed. The animals were killed 24 hours, two, six, and 12 weeks after the procedure. The balloon catheter functioned well and seems suitable for procedures in which a temporary occlusion of the cystic duct is required. Although gallbladders after six and 12 weeks were shrunken and fibrotic, a single treatment of gallbladder sclerotherapy with subsequent catheter removal and no permanent cystic duct occlusion, as performed in this experiment, did not produce complete gallbladder ablation. In this study, sclerotherapy proved safe in the short term, but long-term effects remain to be assessed. PMID- 1938291 TI - The effect of low-osmolar ionic and nonionic contrast media on human blood viscosity, erythrocyte morphology, and aggregation behavior. AB - The effects of three low-osmolar radiographic contrast media (CM)--two nonionic (iohexol, iopamidol) and one ionic (ioxaglate)--on red blood cell (RBC) morphology and aggregation behavior, as well as on blood and plasma viscosity, have been studied. Blood taken from normal, healthy individuals and from patients with uremia was investigated. The authors controlled for the effects of dilution, ionic and nonionic hyperosomolality, and specific chemotoxicity. With ioxaglate, the normal biconcave RBC morphology was fairly well maintained. Iohexol produced a mixture of more-or-less normal cells and echinocytes, while iopamidol yielded only echinocytes. Irregular RBC aggregates have been frequently associated with the presence of echinocyte morphology. In the case of ioxaglate, the capacity of normal blood for rouleaux formation was preserved. This appeared to be compatible with an only moderate decrease in low shear viscosity values. In comparison to the normal control group, RBCs from patients with uremia were clearly more sensitive for hyperosmolar stress. It can be concluded that, in contrast to the nonionic CM, the ionic dimeric compound ioxaglate seems to protect human RBCs against hyperosmolar stress by a mechanism unknown at the present. PMID- 1938292 TI - Magnetic field dependence of longitudinal relaxation rates of solutions of various protein-gadolinium3+ chelate conjugates. AB - Bovine serum albumin (BSA) and porcine serum fibrinogen (FIB) were multiply labeled with gadolinium3+ by using three different ligands: DTPA dianhydride, isothio-cyanato-benzyl-DTPA (ITCB-DTPA), in which none of the five coordinating carboxylates is employed for macromolecular linkage, and isothiocyanatobenzyl TRITA, a macrocyclic ligand. The nuclear magnetic resonance dispersion (NMRD) profiles of the protein-(Gd chelate) conjugates were characteristic to each chelate involved, possessing, as expected, greater longitudinal relaxivities than the corresponding Gd chelates alone and exhibiting prominent peaks at the proton Larmor frequency range of 10 to 40 MHz. Particularly favorable relaxation enhancement was measured in the solutions of BSA-(ITCB-DTPA-Gd) at this field range. When the number of chelates conjugated with protein increased, up to 163 Gd chelates per one fibrinogen, a progressive decrease in relaxivity was observed. This study demonstrates the relaxation properties of novel macromolecular contrast agents designed for magnetic resonance imaging. PMID- 1938293 TI - Petrosal sinus catheterization in sheep. Development of a method for sampling hormonal output from the pituitary. AB - A relatively nontraumatic method has been developed to catheterize the petrosal sinus (PS) of sheep, via the internal jugular vein (IJV), using a percutaneous approach monitored by fluoroscopy. Preselection of suitable animals was facilitated by injecting radiopaque material through a cannula inserted into the deep facial vein to display the venous drainage from the pituitary. Further injections, via the same cannula, were later used to assist in the maneuvering of the catheter/wire guide combination as it passed up the IJV. To confirm catheter placement, plasma samples, collected simultaneously from PS and external jugular vein (EJV), were analyzed for growth hormone (GH). GH concentrations were consistently higher in the PS samples than in those found in the EJV, and more GH pulses were seen in PS samples than in the general circulation. PMID- 1938294 TI - Increasing the scientific quality of clinical efficacy studies of magnetic resonance imaging. PMID- 1938295 TI - In-house testing in emergency radiology. A method for teaching and credentialling radiology residents. AB - Residents frequently learn emergency radiology simply by on-the-job experience. As an educational tool and as a credentialling vehicle, the authors developed an examination consisting of imaging unknowns as well as written questions. The authors have administered the test each of the last three years. After initial apprehension, the residents became comfortable with the annual examination. They now regard the follow-up conferences as the best-organized instruction in emergency radiology in the training program. The authors' experiences suggest that in-house examinations can serve as an important means for teaching and credentialling in emergency radiology. PMID- 1938296 TI - CT in renal and perirenal lymphoma: a further look. PMID- 1938297 TI - Effects of high doses of ioxaglate on proximal tubular epithelial cells in rats. PMID- 1938298 TI - Physician liability and the medical assistant. PMID- 1938299 TI - Urologists stress education. PMID- 1938300 TI - Controversies in urologic oncology. PMID- 1938301 TI - Heart and lungs assessment before sedation. PMID- 1938302 TI - Promoting breastfeeding. PMID- 1938303 TI - Increased multimeric mitochondrial DNA in the brain of scrapie-infected hamsters. AB - We observed a marked increase in multimeric mitochondrial DNA (mtDNA) in brains of scrapie-infected hamsters compared with those of uninfected hamsters. Homogenized brain tissue was subjected to subcellular fractionation to isolate scrapie-associated fibrils and tubulofilamentous structures. Nucleic acids were extracted from the scrapie-associated fibril/tubulofilament fraction which also contained mitochondria. Agarose gel electrophoresis revealed a band corresponding to the size of circular hamster mtDNA in both infected and uninfected samples, but slower migrating bands were observed only in samples from scrapie-infected brain. We showed by molecular cloning, nucleotide sequencing, and Southern blotting that the slower migrating bands are mtDNA. These findings confirm the recent demonstration by differential hybridization that multimeric mtDNA occurs in hamster scrapie brain. Elevated levels of multimeric circular mtDNA have been reported previously in various tumors and cultured cell lines. PMID- 1938304 TI - New data on influenza virus type C confirm its peculiarities as a new genus. PMID- 1938305 TI - Firesetting by young people. PMID- 1938306 TI - The incidence of fire setting and associated psychopathology of children attending a child psychiatric outpatients. AB - Fire setting can be a serious form of anti-social behaviour. A study of 79 consecutive out-patient attenders at a Child Guidance Clinic found a rate of 15 (18.9%). The number of fires set ranged from 1 to 20 (mean 9.9). Conduct disorder was found in 8 (53.3%) of the fire setters. PMID- 1938307 TI - The early results of internal fixation of displaced acetabular fractures. AB - The treatment of choice today for displaced acetabular fractures is anatomical reconstruction by open reduction and internal fixation. Nineteen patients with 20 displaced acetabular fractures treated by this method have been reviewed. A satisfactory outcome was obtained in all but one patient. The surgery is amongst the most demanding in orthopaedics. Specialised radiographic techniques are essential in defining the personality of the fracture and in planning the reconstructive surgery. PMID- 1938308 TI - A change in meningococcal serogroups in the west of Ireland? AB - Admission of patients to University College Hospital, Galway over a five month period commencing December 1989 indicates an increase in the incidence of Neisseria Meningitidis Serogroup C. Seven cases of Group CN. Meningitidis have been identified, five of them occurring over a four week period. A review of Meningococcal isolates occurring at this hospital over eleven years since 1979 shows, serogroup B as the predominant serogroup. Thirty-six isolates identified by serogrouping shows the distribution of serogroups as follows: Serogroup B 69.4%, Serogroup C 19.4%, Serogroup A 8.3%, Serogroup Z 2.7%. Serogrouping, and when available, further serotyping of meningococcal isolates is very important in order to follow epidemiological trends in the disease and to monitor the serogroups that cause outbreaks. This information can influence measures that can be taken in the prevention of spread of the disease as for example the use of vaccination as appropriate. PMID- 1938309 TI - Accelerated retinopathy and nephropathy in diabetic pregnancy. AB - We report a case of severe deterioration in sight despite good metabolic control in a pregnant diabetic patient which has not recovered at two years post delivery. This was accompanied by a deterioration in renal function which similarly has not improved. PMID- 1938310 TI - Better management of Irish hospitals. AB - The establishment of the Dublin Hospitals Initiative and the Efficiency Review Group as first steps in an "action" plan was based on the report in 1989 of the Commission of Health Funding which suggested that "the solution to the problem facing the Irish health services...(lies) primarily...in the way that services are planned, organised and delivered". Our health service is in transition from the phase of facility management into that of functional management. This will involve facing the fact of the limit on resources, introducing information systems and getting the co-operation of hospital doctors. The most senior executive in a hospital must firstly be a good general manager with sufficient power to manage. Hospitals should be divided into centres of responsibility made up of one or more centres of activity. Formal education for hospital administrators should be extended. There is a need for training at all levels, particularly of those administrative and medical staff who have direct interaction with the computer-based system. There should be a commitment to management development particularly by means of teamwork and action learning. PMID- 1938311 TI - Soft tissue and visceral sarcomas in Irish patients. A preliminary report from the Dublin Soft Tissue Tumour Panel. AB - Sarcomas of the soft tissues and viscera are a diverse group of uncommon neoplasms that often present difficult diagnostic and management problems. The Dublin Soft Tissue Tumour Panel prospectively reviewed pathology material from 137 patients of four Dublin teaching hospitals between January 1989 and August 1990. The prevalence of sarcomas in Irish patients was found to be similar to that estimated for the United States. The most common sarcoma of soft tissues was malignant fibrous histiocytoma (14) and the most common visceral sarcoma was leiomyosarcoma (10). The most problematic diagnoses were 3 peripheral neuroepitheliomas (extraskeletal Ewing's sarcomas) which occurred in patients aged 19-27 years, distinctly younger than the typical adult sarcoma patient. Clinical follow-up is in progress and will be combined with the findings of a linked retrospective study, to facilitate evaluation of all aspects of management. PMID- 1938312 TI - The influence of ambient temperature on some commonly measured physiological variables in infants. AB - Fifty-four infants underwent recording of heart rate, respiratory rate, long term and short term heart rate variability and end tidal carbon dioxide measurements at three different ambient temperatures (20 degrees C, 25-26 degrees C, 30 degrees C) under standardized conditions. The infants' skin and rectal temperature remained normal throughout the study. The ambient temperature of the room where the study was conducted significantly influenced the infants' heart rate, respiratory rate and long and short term heart rate variability but not end tidal carbon dioxide values. The thermal environment in which an infant resides has a significant influence on some physiological variables and should be standardized in future physiological studies. PMID- 1938313 TI - Late fetal death--has ultrasound a role to play in its prevention? AB - Late fetal death is the principle cause of perinatal mortality (PNM) in Ireland. Real-time ultrasound scanning has been suggested as a means for identifying the fetus at risk of abnormal pregnancy outcome. Using an ultrasound-based method of fetal assessment the author noted a significant reduction in late fetal death rates over a 4 year period (1985-1988: late fetal death rate: 3.1/1000) as compared to an historic control (1983-84: late fetal death rate: 7.05/10000). In addition, as operator experience increased the false positive test rate (i.e. unnecessary delivery) was noted to fall. It is suggested that real-time ultrasound assessment of the fetus may have some role to play in preventing late fetal death. PMID- 1938314 TI - Outcome of pregnancy following renal transplantation. AB - Successful renal transplantation improves fertility with 1 in 50 women of childbearing age becoming pregnant. Pregnancy following renal transplantation is associated with increased maternal and fetal complications. In Belfast 118 women of childbearing age (15-45 yrs) have received a renal allograft and of these 14 (12%) have become pregnant. Twenty-seven pregnancies have resulted in 23 live births (including one set of identical twins), 1 still birth and 4 first trimester abortions. The most frequent complications were hypertension and prematurity. In this group of patients, whose sole immunosuppressive therapy was azathioprine and prednisolone, pregnancy post transplantation was associated with frequent successful outcome and a low incidence of maternal and fetal complications. PMID- 1938315 TI - A retrospective study of myocardial infarction occurring in elderly patients in a coronary care unit. AB - Myocardial infarction is a major cause of morbidity and mortality particularly in the elderly. Coronary Care Unit monitoring has resulted in the improvement in prognosis in all age groups. In this study, the clinical course and outcome of 204 consecutive patients with acute myocardial infarction aged over 65 years is retrospectively analysed. All patients were managed in a Coronary Care Unit operating a needs related policy. Those under 75 years (120 patients) were compared to those over that age (84 patients). The groups differed in terms of clinical presentation, cardiac enzymatic rise and response to drug therapy. However they had similar complication rates, morbidity and mortality. PMID- 1938316 TI - The Kilkenny Health Project: a community research and demonstration cardiovascular health programme. AB - Ireland has one of the highest death rates in the world from coronary heart disease (CHD) and has not shared in the rapid decline in mortality which has occurred in other countries. The Kilkenny Health Project was established as a community-based research and demonstration programme for cardiovascular disease prevention in County Kilkenny and as a pilot project for future national initiatives. The first phase of the health promotion programme in Kilkenny is being carried out between 1985 and 1990. Changes in behaviour and in factors associated with CHD will be estimated by the difference in changes over time between Kilkenny and the reference area, as measured by independent random sample surveys of men and women aged 35 to 64 years. CHD and stroke events, fatal and non-fatal, will be registered in both areas from 1987-1992. The Project has studied attitudes to CHD and its prevention. Health behaviours have been studied in adults and in post-primary school pupils. Risk factors for CHD have been measured in adults in accordance with the methods of the international MONICA Project. It has been demonstrated that health and education professionals can incorporate preventive activities and health education into everyday practice. PMID- 1938317 TI - Registration of myocardial infarction and stroke in the Kilkenny Health Project: methodology. AB - A myocardial infarction and stroke register was established in January 1987 as part of the evaluation of the Kilkenny Health Project. This is a community programme which aims to reduce risk factors for coronary heart disease. The register records acute myocardial infarction and stroke in residents of County Kilkenny and of the reference county. This will provide accurate estimates of the incidence of these diseases and of trends over time. Methods used comply with the protocol in use by the WHO MONICA Project. This will allow comparison of the incidence of coronary heart disease and stroke in this register with that in other MONICA locations, including that in Belfast, Northern Ireland. Information is obtained from sources in hospitals and the community about relevant history, symptoms and investigations. Information about deaths is also obtained from these sources, and from coroners, death registers and the Central Statistics Office. Appropriate steps are taken to ensure confidentiality of the information. Each event satisfying the MONICA diagnostic criteria for myocardial infarction and stroke is coded in accordance with the MONICA protocol, categorised and registered. PMID- 1938318 TI - Risk factors for coronary heart disease: a population survey in County Kilkenny, Ireland, in 1985. AB - As part of the evaluation of the Kilkenny Health Project, a survey of factors associated with increased risk of coronary heart disease (CHD) was carried out in Kilkenny, Ireland, in 1985. A random sample of 784 men and women aged 35 to 64 years was surveyed. Mean serum total cholesterol was mmol/l in men and women; 7.0% had levels greater than 7.8 mmol/l. Serum total cholesterol was significantly associated with age. 23.4% of males and 23.6% of females were hypertensive. 60.9% of males and 56.4% of females who were hypertensive were not on treatment. The prevalence of regular cigarette smoking was similar in males (27.7%) and females (27.1%). A further 6.3% of males and 1.6% of females smoked cigarettes occasionally or smoked a pipe or cigars regularly. 4.5% had a positive Rose questionnaire for previous myocardial infarction and 3.4% had a positive angina questionnaire. The high median total cholesterol and the low proportion of hypertensives on medication are consistent with findings in other population surveys in the British Isles and with the high mortality rates from CHD in Ireland. The prevalence of hypercholesterolaemia and of untreated hypertension was higher than in population surveys in the United States and Australia where CHD mortality rates are lower and declining at a faster rate than in Ireland. PMID- 1938319 TI - Obesity: a public health problem in Ireland? AB - We examined the prevalence of different categories of body weight in a random sample of men and women aged 35 to 64 years studied in 1985 in County Kilkenny, Ireland. The largest group was those classified as overweight-51.1% of men and 44.7% of women. There were 13.7% of men and 19.2% of women in the obese category. The obese were older but the distribution by social class did not differ significantly from the non-obese. Obese women had significantly more children born alive and a higher prevalence of positive angina questionnaire than those who were not obese. Serum total cholesterol was higher in obese men and HDL cholesterol was lower in obese men and obese women. Systolic and diastolic blood pressures were significantly higher in obese men and women but smoking status was similar. In a multiple logistic regression analysis, systolic blood pressure in men and diastolic in women remained significantly associated with obesity; there was an inverse association between obesity and HDL cholesterol in women and between obesity and HDL-cholesterol as a proportion of total cholesterol in men. A cardiovascular disease prevention programme should seek to prevent the increase in the prevalence of obesity with age which occurs in this population. It would also be important to assess other risk factors for coronary heart disease among those who are obese, with a view to reducing their overall level of risk. PMID- 1938320 TI - Physical activity and risk of coronary heart disease in a survey of adults in Kilkenny, Ireland. AB - A questionnaire survey was carried out to estimate activity levels in a sample of 784 men and women aged 35 to 64 years in County Kilkenny, Ireland. Men were more likely to have sedentary, heavy or very heavy work activity while the majority of women had moderate activity during an average day. Only a small minority of respondents walked or cycled to work. 44% of those surveyed had leisure pursuits which were sedentary. At leisure, a higher proportion of men were involved in active sports or other vigorous activities for at least three hours per week. Men also spent longer each day walking, cycling or jogging. 16.5% of those surveyed engaged in vigorous activities for at least 20 minutes on one to three occasions weekly while 5.1% did so on four or more occasions. Younger people were more likely to take such exercise while older people were more likely to take less vigorous exercise. Path analysis using multiple regression techniques found that an increase in activity levels in this population could lead to substantial reductions in blood pressure, some of which would be mediated through changes in body weight. PMID- 1938321 TI - The Kilkenny Post-Primary Schools Survey--a survey of knowledge, attitudes and behaviour relevant to non-communicable diseases. AB - This survey was carried out in the Spring of 1987 on a stratified random sample of 445 post-primary schoolpupils in County Kilkenny, Ireland. Knowledge, attitudes and behaviour relevant to non-communicable diseases were examined using a questionnaire developed from a World Health Organization core questionnaire. The results showed that levels of adolescent alcohol and tobacco use were similar to those found in neighbouring European countries. Smoking and drinking increased during adolescence and were more prevalent in males. Physical activity decreased throughout adolescence and a high intake of "snack foods" was found. Health related knowledge levels were high but were not related to behaviour. PMID- 1938322 TI - A heart health assessment programme in general practice in County Kilkenny, Ireland. AB - The Kilkenny Faculty of the Irish College of General Practitioners and the Kilkenny Health Project have established a Health Assessment Programme (HAP) to standardise the examination and recording of coronary heart disease (CHD) risk factors in general practice. Criteria were agreed for classification and coding of demographic data, relevant medical history and risk behaviours. Height, weight and blood pressure are measured and venous blood sample is taken for total cholesterol estimation. The assessment is followed by appropriate counselling. The HAP was first targetted at men and women aged 40 to 49 years. During the first 16 months of the programme, 2102 assessments were carried out by 41 general practitioners, which represents 29% of the target group. Those taking part had a lower social class distribution when compared with participants in the KHP baseline survey in 1985. There were no significant differences between the two groups in smoking prevalence or in the distribution of body mass index. Median cholesterol was 5% lower in the HAP group than at the baseline survey. 16% of the HAP clients had diastolic blood pressures of 90 mm Hg or more. The HAP has demonstrated that it is feasible to measure CHD risk factors in a variety of general practice settings. The format facilitates a preventive orientation and has proved acceptable to patients. PMID- 1938323 TI - Trends in mortality from cardiovascular diseases in Ireland. AB - Trends in mortality from cardiovascular diseases in Ireland from 1950 to 1986 are examined and compared with trends in some other developed countries. There was a decline in mortality from all causes which was greater in women than in men. Mortality from coronary heart disease (CHD) increased in males from 1953 to 1974 and has been declining slowly since. Mortality rates in men in Canada and the United States are now lower than those in Ireland and rates in Finnish men are approaching those in Ireland. CHD mortality in Irish males was sixth highest of developed countries in 1985. In women, CHD mortality declined in the 1950s, was stable in the 1960s and early 1970s and has been decreasing slowly since 1974. CHD mortality in Irish women was fifth highest of developed countries in 1985. Mortality rates from cerebrovascular disease have been falling in Irish women since 1958 and in men since 1969. The continuing high mortality from CHD in Ireland warrants the establishment of effective community prevention programmes. PMID- 1938324 TI - The Kilkenny Integrated Oral Health Project. AB - The Kilkenny Health Project, started in 1985, aims to reduce the level of risk factors in the community for coronary heart disease through health promotion. Dental disease and coronary heart disease share risk factors of tobacco use, alcohol consumption and poor dietary patterns. A baseline oral health survey demonstrated significant levels of dental disease in Kilkenny in the 429 adults and 523 children who were examined there in 1987. Seventy one per cent of adults required treatment for periodontal disease and 49% of children surveyed required treatment for dental decay. The Kilkenny Oral Health Project was developed as a community participation project aiming to reduce the level of common risk factors in the community for coronary heart disease and dental disease. It has run parallel with the main Kilkenny Health Project and is one of the first health promotion projects which has an integrated health message preventing dental disease and coronary heart disease. PMID- 1938325 TI - The dialogical dimension in therapists' dreams about their patients. AB - The author develops a conception of the dialogical dimension in therapists' dreams about their patients by using elements of Martin Buber's dialogue philosophy, particularly "Inclusion." By way of illustration, the author discusses one of her cases, and a dream she had about her patient, "The Dream of the Meeting." The dream is interpreted along the lines of the classical countertransference interpretation, the projective identification and the uncovering of the dialogical dimension. The use of dreams as part of "Inclusion" therapy is then discussed. PMID- 1938326 TI - A parent-child day center to welcome the bored mother. AB - A Parent-Child Day Center was started in a small city to cater to the bored mother, and her child(ren). The authors consider several psychodynamic studies on boredom, and propose clinical examples to show the various psychopathological situations involved, and the fact that in these circumstances the libidinal investment of the mother in her child is often absent or inhibited. In these cases, the Day Center appears to be a useful tool for prevention and even treatment. Paradoxically enough, the effectiveness of this tool does not always depend on the significance of the distortion in the relationship between the mother and the child. But when the pathology of the mother is serious, such a place often serves to point out the problem rather than to diminish its consequences on the health and development of the child. PMID- 1938327 TI - Alcohol drinking habits of Israeli Jewish, Moslem and Druze adolescents in the north of Israel in 1990. AB - The article describes research conducted in the north of Israel on the drinking and smoking habits of 2,763 Moslem, Druze, Kibbutz and urban Jewish adolescents from a big city and a development town. It compares alcohol drinking frequencies (alcohol drunk on a single occasion) and amounts of these four youth populations, as well as cigarette smoking, and hashish use. Also students were asked about the drinking patterns of parents and best friends. PMID- 1938328 TI - Why we were silent--an Israeli psychiatrist speaks to Germans on psychic pain and past persecution. AB - Professor Dasberg, the Elie Wiesel professor at the Bar Ilan University and the co-founder of "Amcha", delivered this speech at the Humboldt University in Berlin on the anniversaries of the Kristalnacht and the recent unification of Berlin. Professor Dasberg was serving as the president of The Israel Psychiatric Association at the time. PMID- 1938329 TI - Verbal hallucinations in psychotic patients. AB - "Verbal hallucinations" are sentences that psychotic patients may say repeatedly throughout a conversation which are out of context or unconnected to the topic of conversation. These hallucinations are not the outcome of a remembrance of an experience or an event and do not bring about any emotional relief or catharsis, but they supply valuable information. They resemble Jacques Lacan's description of the psychotic mechanism "Forclusion." This mechanism relates to experiences that did not undergo the process of primary symbolization through language, and experiences where words were attached but were not bound to the language structure. The result being that these experiences did not enter into the unconscious discourse of the subject. This information can reappear as verbal hallucinations in the psychotic patient. In such cases, the therapist, with the assistance of the patient's family, must investigate the meaning of the verbal hallucinations through research into the patient's and family's history in the phase prior to language development. When such a connection is discovered, the therapist must then bridge the hallucinations with the events unknown to the patient but contained in his subconscious. The therapist's role in such cases resembles that of a parent with a child: To translate the subject's experience through language from the physical schema to the body image and symbolic plane and in so doing, give meaning to meaninglessness. In our paper three short clinical cases are presented. PMID- 1938330 TI - Solar activity and admissions of psychiatric inpatients, relations and possible implications on seasonality. AB - Admission data for a month, from a single psychiatric unit, were examined for over 1800 psychiatric inpatients during the period of 1977 to 1987, to assess their correlation with 10 parameters of geophysical activity. This pilot study indicates two statistically significant correlations between the numbers of first psychiatric admissions per month and the level of solar radioflux in the corresponding month (p less than 0.05) and sudden magnetic disturbances of the ionosphere (p less than 0.01). There is a statistically significant inverse correlation between the number of first psychiatric admissions per month, with the index of geomagnetic activity (GMA) (p less than 0.05) and with the number of hours of positive ionization of the ionosphere in the corresponding month (p less than 0.01). PMID- 1938331 TI - Risk-benefit ratio: the soft underbelly of patient autonomy. PMID- 1938332 TI - The inability to swallow as a fatal pathology: comments on the McHugh/O'Rourke correspondence and the removal of life-sustaining treatment. PMID- 1938333 TI - "Current controversies in the right to live, the right to die II." Case for consideration in symposium. PMID- 1938334 TI - Death by deliberate dehydration and starvation: silent echoes of the Hungerhauser. PMID- 1938335 TI - The case of Mr. Stevens. PMID- 1938336 TI - Getting down to cases. PMID- 1938337 TI - Concerning the case of "Mr. Stevens.". PMID- 1938338 TI - Locus of control and depression as a function of sex role orientation in two age groups of mental health nurses. AB - The purpose of the study reported in this article was to examine the relationships between locus of control and level of depression in younger adult and midlife registered mental health nurses (MHNs) in relation to each other and as a function of sex role orientation. On the basis of C. G. Jung's (1954) theory of individuation, the following hypotheses were derived: (a) MHNs with an androgynous sex role orientation will have a higher internal locus of control than MHNs with a nonandrogynous sex role orientation; (b) MHNs with an androgynous sex role orientation will be less depressed than nonandrogynous sex role-oriented MHNs, and (c) midlife MHNs will be more androgynous in sex role orientation than younger MHNs. Thirty-six participants, all working female registered mental health nurses between the ages of 30 and 59, were placed in the midlife group (age 41-59) or the young adult group (age 31-40) on the basis of self-indicated age. Two groups of female MHNs (younger adult and midlife women) were compared with each other by means of the Personal Attributes Questionnaire (Spence, Helmreich, & Stapp, 1975), used to assess sex role orientation (androgynous or nonandrogynous: cross-typed, sex-typed, or undifferentiated); Rotter's (1966) Locus of Control Scale, used to assess internal or external (I-E) locus of control; and the Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961), used to assess level of depression. In regards to all three hypotheses, no statistically significant associations were found among the study variables. The strengths and weakness of the present study were reviewed. The theoretical and practical implications of the results were discussed, and directions for future research were considered. PMID- 1938339 TI - Anxiety, depression, quality of life, and self-care among survivors of myocardial infarction. AB - This article examines the relationship between anxiety, depression, quality of life, and performance of suggested self-care behaviors among older adult myocardial infarction survivors. Interviews were conducted with 94 adults aged 65 years and older. The Profile of Mood States was used to measure anxiety and depression. Quality of life was measured with the Perceived Quality of Life scale. The Health Behavior Scale was used to measure performance of suggested self-care behaviors (modify diet, administer medications, manage stress, exercise, and reduce smoking). Depression scores accounted for 49% of the variance in quality of life scores. Depression scores predicted each of the self care behavior scores. Anxiety scores did not predict quality of life scores or any self-care behavior score. Findings suggest that mental health interventions should become an integral part of formal cardiac rehabilitation programs soon after the infarction; interventions for depression long after the infarction are needed as well. PMID- 1938340 TI - Degree of cognitive distortions and level of depression in bulimic patients. AB - A descriptive correlation design was used to study the relationship between the degree of cognitive distortions and the level of depression in bulimic patients. The theoretical framework was based on Beck's (1976) cognitive theory of depression. Beck viewed symptoms of depression as consequences of distorted thought processes. The instruments that were used to measure the study variables were the General Cognitive Error Questionnaire (Lefebvre, 1981) and the Beck Depression Inventory (Beck, Rush, Shaw, & Emery, 1979). The hypotheses for the study predicted that there would be a positive relationship between the degree of cognitive distortions and the level of depression in bulimic patients. The Pearson r was used to determine if a statistically significant relationship existed between degree of cognitive distortions and level of depression. Data analysis revealed that there was a significant relationship, r(28) = .586, r2 = .343, p less than .001, between the degree of cognitive distortions and level of depression in this study of 30 bulimic patients. PMID- 1938341 TI - Psychiatric nursing education in Nebraska: 1989-1990. AB - The academic and clinical content of psychiatric nursing curricula in the registered nurse basic educational programs in Nebraska for academic year 1989 1990 was explored by the Nebraska Sub-group of the Nursing Curriculum and Training Task Force of the National Alliance for the Mentally Ill. The review includes literature regarding the history, development, and future trends of psychiatric nursing; factors affecting nursing student attitudes toward psychiatric patients; basic content included in psychiatric and psychosocial nursing curricula; and concepts essential in working with the seriously, persistently mentally ill. Contrary to current trends in the United States, all Nebraska schools of nursing have a generic psychiatric nursing course taught by clinical specialists in psychiatric-mental health nursing. Hands-on clinical time spent with patients with psychiatric diagnoses as well as those with psychosocial needs varies from 84 to 200 hr per semester. Not all students are exposed to patients with severe and persistent mental illness. Fewer than 5% of Nebraska graduates choose psychiatric nursing as their area of practice. The authors express grave concern for the future of psychiatric nursing education. Implications for curriculum revision and replication studies are suggested. PMID- 1938342 TI - Historical perspectives on women and mental illness and prevention of depression in women, using a feminist framework. AB - This article discusses Showalter's (1985) description of the historical perspectives of how women have been viewed in the culture and how these perspectives have influenced women's past treatment for mental illness. Using Caplan's (1974) level of prevention in health care and a feminist framework, suggestions are made for prevention or alleviation of depression in women in the contemporary culture. In The Female Malady, Showalter (1985) described three themes that were prevalent through three historical phases of English psychiatry: psychiatric Victorianism (1830-1870), psychiatric Darwinism (1870-1920), and psychiatric Modernism (1920-1980). Showalter described how the prevailing attitudes toward the mentally ill, and toward women in particular, were influenced by the social changes of each historical phase and how these attitudes affected the thinking and treatment used by the psychiatrists. The problems that these historical perspectives have caused for women are discussed. A feminist view of depression is given in which depression is equated with oppression. The guidelines for feminist therapy developed by the Task Force of the Feminist Therapy Collective, Inc., of Philadelphia and by feminist therapists in private practice in Philadelphia are discussed as an alternative to the traditional approach to therapy. Mental health promotion using Caplan's (1974) three levels of prevention in health care is discussed. Intervention strategies for each of these levels of prevention, following feminist guidelines and using techniques that have been found to be helpful for women, are described and discussed. The focus of these intervention strategies is to reduce effects of factors in the cultural environment that contribute to the oppression of women and, in turn, contribute to their becoming depressed. PMID- 1938343 TI - Ethical problems encountered by mental health nurses. AB - This descriptive study examines ethical conflicts reported by psychiatric-mental health nurses in community and inpatient settings. Generalist community nurses were included for comparison. The analysis of cases included reviewing general descriptions of the cases and identifying decision maker, principles involved, and type of moral conflicts. Fifty-seven case situations were collected: 20 cases from a psychiatric hospital, 18 cases from community mental health programs, and 19 cases from a general public health program. Fifty-one of the 57 cases reflected ethical problems. Using Jameton's (1984) categories, 30 of the 57 cases were rated as a dilemma, 18 were rated as moral uncertainty, and 3 were rated as examples of distress. The mental health nurses indicated that they believed they were the decision maker in the majority of cases. The general community nurses were more likely to believe the client was the decision maker. The identified principles, based on Veatch and Fry (1987), were doing good, or beneficence (26); confidentiality (10); autonomy (9); avoiding deception (4); and preventing killing (2). In the remaining 6 cases no principles were identified. Staff conflict was present in 13 of 20 inpatient cases, as compared with only 3 cases in each of the community settings (p less than .005). PMID- 1938344 TI - Rich cases. The ethics of thick description. PMID- 1938346 TI - Helga Wanglie's ventilator. PMID- 1938347 TI - The limits of a wish. PMID- 1938345 TI - The chief of medicine. PMID- 1938348 TI - The significance of a wish. PMID- 1938349 TI - Medical futility, medical necessity. The-problem-without-a-name. PMID- 1938351 TI - Life, liberty and the pursuit of offspring. PMID- 1938350 TI - When is home care medically necessary? PMID- 1938352 TI - Uncertainty and the shaping of medical decisions. PMID- 1938353 TI - Median mandibulotomy: a critical assessment. AB - Median mandibulotomy (mandibular "swing") has supplanted mandibular resection for access to oral and oropharyngeal tumors when there is intervening grossly normal tissue between the tumor and bone. It has also proved useful for exposure in selected patients with deep lobe parotid or parapharyngeal space tumors. We have reviewed our experience with 313 mandibulotomies performed between 1959 and 1988 with emphasis on indications, complications, and modifications in technique. Most of our mandibulotomy patients had an uncomplicated recovery, but osteotomy related complications occurred in 20%. These complications were usually minor and no instances of nonunion were recorded. There was no apparent relationship to antecedent or postoperative radiotherapy. Dental splints were used only in selected patients (40%). The technique of osteotomy has been evolving in recent years. Paramedian, rather than median mandibulotomy, minimizes trauma to the genioglossus, geniohyoid, and digastric muscles. Miniplates offer a useful alternative to conventional wire fixation. Preoperative dental assessment has facilitated better occlusion postoperatively in dentulous patients. PMID- 1938354 TI - Modified mandibular swing procedure for resection of carcinoma of the oropharynx. AB - For most patients, the primary approach to carcinoma of the oropharynx has been with radiotherapy. We describe a modification of a mandibular swing procedure for resection of oropharyngeal lesions. This modification included a mandibulotomy that began in a staircase manner in the midline and extended laterally toward the ramus of the mandible to protect a long, fixed dental bridge. It also included the preservation of the mental nerve by unroofing the mandibular canal. No morbidity was associated with this procedure. PMID- 1938355 TI - Preoperative evaluation of the mandible in patients with carcinoma of the floor of mouth. AB - Preoperative evaluation of the mandible for invasion by tumor has always been a difficult problem. Various methods have been used, including clinical evaluation, panoramic x-rays, dental films, routine mandible films, bone scans, computed tomographic (CT) scans, and magnetic resonance imaging (MRI) scans. The diagnostic accuracy of these methods has not been totally satisfactory from the clinical standpoint. We compared the diagnostic effectiveness of clinical evaluation, panorex films, and CT scans in 60 patients with carcinoma of the floor of mouth. The relative value of these tests was studied in relation to marginal or segmental mandibulectomy. Our data showed that CT scanning was not very helpful, mainly because of the presence of irregular dental sockets and artifacts. Clinical evaluation was the most accurate, both to determine bone invasion and to decide the type of mandibular resection necessary in association with the primary tumor. Panoramic films were helpful in evaluating the gross extent of mandibular invasion. However, they were not of any help in determining minimal bony invasion or cortical invasion. Even though CT scanning has made a tremendous impact in other areas of head and neck surgery, it is not of much help in making the critical decisions in the type of mandible resection, marginal or segmental, in patients with carcinoma of the floor of mouth. Our experience demonstrates that clinical evaluation is superior in preoperative evaluation of the mandible, and especially in deciding the type of mandible resection. PMID- 1938357 TI - Value of needle biopsy in directing management of parotid lesions in HIV-positive patients. AB - Fourteen human immunodeficiency virus (HIV)-positive patients with parotid enlargement were reviewed retrospectively in order to elucidate the natural history of this clinical entity. The efficacy of fine-needle aspiration (FNA) in predicting benign nonsurgical disease was evaluated. The most common findings on FNA were proteinaceous fluid and/or epithelial cells consistent with cyst contents in 71% of the patients, followed by reactive lymphadenitis (50%), and chronic or granulomatous inflammation (21%). No evidence of malignancy was seen in any patient. These results correlated well with the histopathologic diagnosis in all operated patients. Surgery did not affect the ultimate clinical outcome. This study suggests that HIV-positive patients with isolated asymptomatic parotid swelling in the absence of other clinical features suggestive of malignancy can be followed conservatively with FNA, avoiding the risks of surgery. PMID- 1938356 TI - Glottic cancer involving anterior commissure: surgery vs radiotherapy. AB - A retrospective review of 182 patients with glottic cancer involving the anterior commissure (AC) is presented. Of these, 123 patients were first treated with conservative surgery and 59 underwent radiotherapy. Patients were staged according to the AJCC system and by the modality of neoplastic involvement of AC (pure AC cancer, glottic cancer involving AC up to the midline, and beyond the midline). Our results indicate a higher rate of local control and of specific disease survival in the group of patients first treated with surgery than those treated with radiotherapy (86% vs 74% and 97.5% vs 84%, respectively) (p less than 0.05). For pure AC cancers, our results show better local control with primary radiotherapy than with conservation surgery (82% vs 76.5%), but surgical failures have been more successfully salvaged than have radiotherapy recurrences (ultimate local control, 97.5% vs 82%, respectively). These data suggest that the treatment of choice for AC cancers is conservation surgery, particularly frontolateral laryngectomy. PMID- 1938358 TI - Chemotherapy rapidly alternating with accelerated radiotherapy for advanced carcinomas of the hypopharynx and upper esophagus: a feasibility study. AB - Patients with advanced carcinomas of the hypopharynx or upper esophagus have among the worst prognoses in head and neck oncology. We developed a treatment regimen of rapidly alternating multi-agent chemotherapy and accelerated interrupted radiotherapy as follows: Three cycles of chemotherapy were delivered [day 1, cisplatin 100 mg/m2; days 1-4, 5-fluorouracil (5-Fu) 900 mg/m2] and repeated every 3 weeks. On day 8 of each chemotherapy cycle radiotherapy was started, consisting of 10 fractions of 200 cGy delivered twice daily, for 5 days. The total dose of radiotherapy was 6,000 cGy over 7 weeks, and the total duration of chemotherapy and radiotherapy was 8 weeks. Nineteen patients with locally advanced, epidermoid carcinoma of the hypopharynx (9 patients) or upper esophagus (10 patients) were treated on this protocol. Minimum follow-up was 1 year. Twelve patients had tumors judged technically unresectable, whereas 7 had tumors considered resectable only with total laryngectomy, which was unacceptable to the patients. One patient died of nadir sepsis during treatment, but otherwise the acute toxicity was relatively mild (grade I/II in 16 patients, grade III/IV in 3 patients). The complete response rate was 83% (15 of 18 patients), and the partial response rate was 17% (3 of 18). No patient failed to respond. The survival rate was 80% at 1 year and 73% at 18 months. At 1 year, 89% of the patients remained in remission and at 18 months, 74% Late complications occurred in 4 patients. These included laryngeal necrosis, pneumonitis, esophageal stricture, and tracheoesophageal fistula.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938359 TI - Thyroid-stimulating hormone levels after radiotherapy and combined therapy for head and neck cancer. AB - Sixty-eight patients were studied prospectively with serial thyroid-stimulating hormone (TSH) levels after radiotherapy for head and neck neoplasms. Overall, 57% of the patients developed elevated TSH levels. Excluding patients with less than 2 years follow-up, 85% developed an elevated TSH. Ninety-two percent of patients treated with partial thyroidectomy and radiotherapy developed an elevated TSH. Most TSH elevations occurred within 1 year of treatment. The dose of radiotherapy used and the performance of hemithyroidectomy were related to the development of elevated TSH levels (p less than 0.05). The performance of radical neck dissection, gender, hyperfractionated radiotherapy and the use of chemotherapy were not related to the development of an elevated TSH (p greater than 0.05). PMID- 1938360 TI - Miniplate fixation of zygomatic fractures. AB - The availability and application of miniplate systems for the repair of displaced zygomatic fractures may effect commonly accepted guidelines for fixation of these injuries. A retrospective review of 20 patients at New York University-Bellevue Medical Center was conducted to further delineate issues concerning surgical repair and fixation. Our experience with one- and two-point fixation is evaluated and guidelines are presented. PMID- 1938361 TI - Carcinoma of the skin metastatic to parotid area lymph nodes. AB - This is a retrospective analysis of 60 patients with previously untreated metatypical basal cell (3 patients) or squamous cell (57 patients) carcinoma of the skin, metastatic to the parotid area. All patients had a minimum 2-year follow-up, and 43% had a minimum 5-year follow-up. Treatment was surgery alone (8 patients), irradiation alone (16 patients), or planned combined surgery and irradiation (36 patients). The ultimate rates of control of disease in the parotid area were surgery alone, 5 of 8 (63%); irradiation alone, 6 of 13 (46%); planned combined surgery and irradiation, 32 of 36 (89%). In the combined-treated group, all 4 recurrences were in patients who had positive surgical margins and gross involvement of the facial nerve. In patients with negative surgical margins, without involvement of the facial nerve, who had combined treatment, the control rate was 100%. Of the surgery-alone group, only 1 patient ultimately had the disease controlled and retained a functioning facial nerve. PMID- 1938362 TI - Nodular fasciitis of the oral mucosa: light and electron microscopy study. AB - Nodular fasciitis of the oral mucosa is a rare lesion. The present article describes an additional case and discusses the difficulties in the histologic diagnosis. The final diagnosis is based on immunohistochemistry and electron microscopic morphology. Nodular fasciitis should be considered in the differential diagnosis of swellings in the oral mucosa. PMID- 1938363 TI - Neurilemmomas of the cervical vagus nerve. AB - Four patients were seen with neurilemmoma which arose in the cervical vagus nerve. Three tumors arose in the upper third of the lateral neck, and the remaining one in the lower third. Lateral neck mass was a prominent symptom in 3 patients, and parapharyngeal mass in the remaining one. The parapharyngeal mass bulged into the oropharynx in the tonsillar and retrotonsillar region and caused mild swallowing difficulty. Complete surgical extirpation by means of intracapsular enucleation was possible in all 4 patients. All patients remained free of disease for periods ranging from 15 to 75 months following surgery. It would appear that an intracapsular enucleation may be advisable for clearance of this kind of tumor. PMID- 1938364 TI - Conservation surgery for inverted papillomas. AB - To evaluate the role of conservation surgical treatment of inverted papillomas of the nose and paranasal sinuses, the clinical course of 46 patients treated during a 10-year period was evaluated. Twelve patients were noted to have either invasive squamous cell carcinoma or carcinoma in situ and were excluded from analysis. Of the remaining 34 patients, 19 had previous treatment for inverted papilloma. Subsequently, 20 patients were treated with lateral rhinotomy and medial or partial maxillectomy. Fourteen patients were treated with conservation surgical therapy. There were 5 recurrences (15%), which all occurred in the conservation-treated group. Four of six (66%) patients treated with an intranasal procedure recurred but only 1 of the 8 (12%) patients treated with a Caldwell-Luc approach combined with an intranasal procedure. Successful treatment was achieved in all patients undergoing salvage surgery for recurrence. The role of conservation treatment in the management of inverted papillomas of the nose and paranasal sinuses is discussed. PMID- 1938365 TI - Hurthle cell carcinoma of the thyroglossal duct. AB - A thyroglossal duct cyst is an embryologic remnant that often manifests as a swelling in the midline of the neck. The development of a carcinoma in a cyst is rare but well recognized. The majority of those reported are papillary carcinoma; there have been 4 cases of mixed follicular-papillary (which biologically and clinically behaves as a papillary carcinoma) and only 1 follicular. A computer search of the literature revealed no previous report of a Hurthle cell carcinoma arising in a thyroglossal duct. A case of Hurthle cell carcinoma arising in a thyroglossal duct is presented, and the pathology, clinical manifestations, and management are reviewed. PMID- 1938366 TI - Aneurysm of the internal jugular vein manifesting after prolonged positive pressure ventilation. AB - True internal jugular vein aneurysms are exceedingly rare anomalies. To date very few case reports have appeared regarding this entity. We present a case of a congenital internal jugular venous aneurysm which manifested itself after abdominal surgery and prolonged positive pressure ventilation. A theory regarding its manifestation is presented. We believe this case to be unique in its presentation. PMID- 1938368 TI - Aneurysmal bone cyst of the cricoid cartilage: an unusual cause of subglottic stenosis. AB - Aneurysmal bone cysts (ABC) are locally aggressive bony tumors which rarely occur in the head and neck. Only 3 cases have been reported in the larynx previously, 1 involving the cricoid cartilage. A patient is presented who developed subglottic stenosis with airway compromise due to an ABC arising from the cricoid cartilage. The literature on bony tumors of the laryngeal cartilages was reviewed and the clinical and pathologic findings in this case highlighted. PMID- 1938367 TI - Giant Teflon granuloma of the larynx. AB - Endolaryngeal injection of Teflon paste to augment and medialize the paralyzed hemilarynx aims to improve dysphonia and relieve aspiration. After an initial short-lived inflammatory reaction in the laryngeal tissues, a foreign body granuloma forms around the Teflon. In most cases the results are good but it may occasionally be necessary to consider removal of the granuloma if too large a volume has been injected, if it is inappropriately placed, or if the paralyzed vocal cord subsequently recovers. Surgical removal is difficult and the results are unpredictable. This case illustrates, for the first time, that evaluation using both a high-resolution computed tomographic (CT) scan and endoscopy with telescopes permits satisfactory assessment before removal of Teflon. PMID- 1938370 TI - Comparison of geriatric day hospitals in Fife. PMID- 1938369 TI - T-tube modification to decrease the risk of plugging. AB - Laryngotracheal stenosis is a recognized complication of local injuries, such as prolonged intubation. Surgical reconstruction with the use of a tracheal T-tube is widely recommended. We report a serious complication consisting of the sudden obstruction of the T-tube by viscous secretions. In order to prevent this undesirable consequence, a simple modification of the T-tube technique is proposed. PMID- 1938371 TI - A home care service for terminally ill patients in Edinburgh. PMID- 1938372 TI - Anti-smoking policies and practice in Scottish Health Boards: progress 1985-89. Scottish Tobacco Group. AB - 1. The anti-smoking policies in practice of Scottish Health Boards (HBs) were surveyed in 1989, and the results compared to those of a previous survey in 1985. 2. There has been reasonable to good progress in production of a HB policy document; in smoke-free HB committee meetings; in smoke-free public offices, hospital offices, canteens, hospital outpatient areas, community clinics, health centre waiting rooms and offices: in prohibiting sale of cigarettes on NHS premises; in provision of smoking cessation services; in liaison with other organisations; and in initiatives on National No-Smoking Day. 3. On the other hand progress has been poor in providing a smoke-free environment in acute, maternity and longstay wards, and especially poor in hospital ward sitting up areas. There has been disappointingly little progress in the education of nurses and only minor improvement in that for paramedical and lay staff. PMID- 1938373 TI - Setting priorities: a framework for the assessment of health care priorities in Scottish Health Boards. PMID- 1938374 TI - Out of hours work in primary care: audit of an urban co-operative deputising service. AB - The White Paper and discussions about the GP contract have reinforced an interest in the audit of the demand for and the quality of out-of-hours cover. We audited deputising service records for the North East Deputising Service in Glasgow over one year. Six thousand eight hundred and thirty-four calls were received from a catchment population of 37,300. A sample of 468 (7%) calls was used to estimate the appropriateness of calls. A classification, based on diagnosis, classified calls as emergency, 'reasonable' or 'unnecessary'. One hundred and eighty-three out-of-hours calls were made per 1,000 patients per year, with 40 of these being at night. Twenty-three per cent of calls were considered unnecessary, 65% reasonable and 12% genuine emergencies. People living in areas of deprivation were more likely to call and more likely to make an inappropriate call. Only 1% of calls ended with telephone advice. Five per cent had to wait more than two hours after calling. The rate of calls in this study was high compared to other studies and the use of telephone advice low. Attempts should be made to make more use of telephone advice and to educate patients to make more appropriate use of services. However, the high demand from areas of deprivation should be borne in mind when calculating GP budgets. PMID- 1938375 TI - Infertility: the experience of a tertiary referral centre. PMID- 1938376 TI - Day case surgery for children. PMID- 1938377 TI - The history of the International Classification of Diseases. AB - A major purpose for gathering descriptive statistics is to allow comparisons of data over time and among different places. In the case of public health it has been particularly important to make such comparisons utilising diagnostic information. Without a standard measuring tool which remains fixed for periods of time and which is applied uniformly from place to place, meaningful comparative analyses of diagnostic information would not be possible. The International Classification of Diseases is such a standard tool. This presentation briefly traces the history of the development and revision of various versions of this International Classification of Diseases and presents the background leading to the current activities associated with the Tenth Revision of this important health statistical and epidemiological disease classification. PMID- 1938378 TI - A community-based study into the possible reasons for the high incidence of cardiovascular disease in the west Highland District of Lochaber. AB - Cardiovascular screening of 726 males in a Fort William group practice was undertaken in an effort to determine possible causes for the high incidence of cardiovascular disease in the area. Sixty-four per cent of those sampled were born outside the area. The mean fasting plasma cholesterol level was surprisingly low at 5.4 mmol/l. Forty-three per cent of the sample were smokers and 22% had diastolic blood pressures above 90 mm Hg, 24% were clinically obese and 29% had a history of ischaemic heart disease amongst first degree relatives. Public awareness of cardiovascular risk factors was found to be low. A local health education programme could prove to be of great benefit. PMID- 1938379 TI - Death certification and mortality statistics. PMID- 1938380 TI - Deaths in Scotland during the 1989-90 influenza epidemic. PMID- 1938381 TI - Malignant melanoma in Scotland: trends in incidence and survival, 1968-87. A review prepared by the CSA Information and Statistics Division for the Health Monitoring Group. PMID- 1938382 TI - Patterns of presentation of breast disease over ten years in a specialised clinic. AB - A clinic specialising in breast disease has been surveyed over a decade. Detailed information has been collected on 3,500 women with benign breast disorders and 950 with breast cancer. Over this time, the demand for and utilisation of this facility has increased steadily. Over the ten years, there has been a trend for a higher proportion of breast cancers to be smaller in size and for fewer cancers to be locally advanced or metastatic at presentation. Critical appraisal of referral and consultation patterns indicates that the original aims of establishing this clinic have not been maintained. Paradoxically, this is a result of the success of the exercise. Measures which might lead to a higher proportion of patients with breast cancer being managed at the Breast Clinic rather than a General Surgical Outpatient Clinic are discussed. PMID- 1938383 TI - Accidents, poisoning and violence as a cause of hospital admissions in children. AB - A study has been carried out to assess the pattern of child admissions to Tayside Hospitals as a result of accidents, poisoning and violence (hereafter referred to simply as 'accidents') during 1989, and to determine if any major changes have taken place since 1980. The length of stay resulting from each class of accident was used as an approximate indicator of severity and the consumption of Health Service resources. In 1989, 1,388 of Tayside's 70,609 children were admitted to hospital as a result of accidents. With a total of 4,140 days spent in hospital, an average of 11.3 beds are constantly occupied by child accident victims (not including the long-term disabled). Falls resulted in the largest number of admissions to hospital, with poisoning, and having been accidentally struck by persons or objects, in second and third place. Analysis of bed usage, however, revealed a different pattern. While falls remained the biggest consumer of bed days, these were now followed by motor vehicle traffic accidents (MVTAs) and scalds. The average length of stay for MVTAs and scalds was 9.1 and 9.0 days respectively compared with an average of 2.8 days for all types of accident. Poisoning and scalds showed a remarkable age dependence with 81% of children admitted for poisoning or suspected poisoning being in the 1-3 year age group, and 63% admitted for scalds under the age of two. PMID- 1938384 TI - The state of general practice computing in Scotland and the characteristics of computerised practices: a survey of 948 practices. AB - A survey of 1,179 Scottish practices produced an 81% response rate and gathered data about practice size, environment, state of computerisation as well as future plans for the use of computers in the practice. Results show that the majority of practices are already computerised and that over 90% will be computerised soon. A computer in the practice correlates especially with the presence of a practice manager, a practice nurse and training or teaching status. Scotland is unique in having a national software program (GPASS) for general practice administration. We estimate that by mid 1991 over 750 practices will be using GPASS. PMID- 1938385 TI - An analysis of the trainee year in general practice. AB - A survey of 12,425 trainee consultations is reported. Chronic illness only constituted 19.4% of their workload. The greatest number of consultations occurred with younger patients in the 20-30 age group. Only a small proportion of consultations involved anticipatory care and health education (0.3% and 1.1% of total workload respectively). Women patients showed a strong preference to consult a female doctor with twice as many seeing a lady trainee in preference to a male doctor. The study has implications for teaching and learning during the trainee year in general practice. PMID- 1938386 TI - A bibliographic database and information retrieval system in prosthetics and orthotics. PMID- 1938387 TI - Ambulatory surgery and the hospital. AB - Ambulatory surgery can be a win-win proposition for patients, physicians, payers, and even for hospitals. The main elements at risk are high costs and the traditional models of hospital-based surgical care. If hospitals delay their responses to the challenges of the free-standing surgicenter, the latter will become as common as the multispecialty group practice. Health care institutions need to address some questions in responding to this trend: how hospitals should act to transform their bureaucratic, inefficient systems; who should assume the leadership role; and how much autonomy and pluralism will be appropriate. PMID- 1938388 TI - Hospital schools: a primer on management models and policy implications. AB - This three-part article, a primer on hospital schools for hospital administrators, discusses laws, student constituencies, epidemiologic trends, and hospital school services; describes hospital school organizational models; and discusses policy implications. PMID- 1938389 TI - Are managers compensated for hospital financial performance? AB - Management compensation in a sample of 213 nonprofit hospitals in Ontario, Canada, is examined. Management compensation is determined first and foremost by hospital size and teaching status. Results indicate only a weak relationship between management compensation and hospital financial performance. PMID- 1938390 TI - Not-for-profit not equal to no profit: profitability planning in not-for-profit organizations. AB - Contrary to common understanding, not-for-profit organizations must earn a profit in order to maintain fiscal solvency. This article presents a methodology to determine the appropriate profitability target with illustrations presented for a health maintenance organization. PMID- 1938391 TI - New perspectives on our national health care dilemma. AB - Continued debate over who should pay for the increasingly unaffordable U.S. health care system has failed to yield a consensus solution. Shifting attention to how to reduce health care costs may be more productive. Strategies for achieving this goal include drastically reducing costly quality deficiencies, eliminating higher cost care options that add no demonstrated value, recognizing that responsibility for clinical and cost consequences cannot be divided, and acknowledging that rationing available resources is superior to other allocation alternatives. PMID- 1938392 TI - Ethical considerations for business relationships of hospitals and physicians. AB - As more hospitals and physicians seek to establish joint business-based ventures, their ethical consequences are being sidestepped. As a result, the traditional ethical expectation of a patient's well-being as the primary concern in providing medical care appears to be replaced by hospital and physician financial interests. So legislation is likely to be enacted to prevent any business relationships between hospitals and physicians. PMID- 1938393 TI - Leasing capital assets and durable goods: opinions and practices in Florida hospitals. AB - Although leasing is a major source of financing for hospital capital acquisitions, the rationale for choosing leasing over conventional financing is not clear. This article examines academic and leasing company views, and then surveys hospital executives to obtain their views. PMID- 1938394 TI - [Delayed immediate-type reaction versus type-III reaction: pathophysiologic differentiation and clinical relevance]. PMID- 1938395 TI - [Nevus associated malignant melanomas--diagnostic validation and prognosis]. AB - The diagnosis and prognosis of naevus-associated malignant melanomas are examined in the present study. For this purpose, 581 cases of primary malignant melanoma seen in the University Department of Dermatology, Berlin Steglitz, were histologically investigated for naevus association. A naevocytic association was proven in 135 (23%) of the malignant melanoma biopsies. Naevocytic malignant melanomas were found at a significantly higher rate (P less than 0.01) in patients under 50 years of age. The 5-year survival rate for naevocytic melanomas was not significantly different from that for other malignant melanoma types: around 80% in both groups. An immunohistological evaluation of the diagnosis of naevus-associated melanoma was also performed on the basis of specimens from 89 melanocytic lesions. The use of HMB-45 for diagnosis of melanocytic tumours made it possible to differentiate resting dermal naevus cells from malignant melanoma infiltrates in paraffin sections in the present study, thus simplifying the diagnosis of naevus-associated malignant melanomas. However, dysplastic naevi, junctional naevi and juvenile melanomas are also stained by HMB-45, which means that malignant melanomas associated with junctional melanocytic naevi still cannot be reliably identified even today. PMID- 1938396 TI - [The patient with polymorphous light dermatosis. Skin type, hardening and other light-associated markers]. AB - From 1985 to 1989 we interviewed 312 patients suffering from polymorphous light eruption (PLE). The interviews were based on a questionnaire dealing with the various light-dependent factors that exacerbate the disease. Of 90 patients who were tested with artificial UV-A and UV-B irradiation sources, 60 reacted with typical PLE lesions: (a) 27 patients to UV-A alone, (b) 12 to UV-B alone, and (c) 21 to both UV-A and UV-B. Using UV-A provocation tests we were able to determine the anamnestic criteria indicating a possible UV-A induction of PLE, e.g. occurrence in the shade, no protection from window glass, no benefit from conventional sunscreens, and occurrence in solaria. The period from experimental irradiation to induction of skin lesions was shorter in skin types I and II than in skin type III and IV. Hardening phenomenon was reported by 37% of our patients. Of the UV-A-positive patients, 38% showed the first presentation of PLE lesions at the height of summer, as against 64% of the total number of patients questioned. Additional lesions at non-irradiated skin sites occurred in 25% of our patients, the frequency rising with increasing duration of the tendency to PLE. PMID- 1938397 TI - [The value of symptoms and findings in urethral Chlamydia trachomatis infection]. AB - The history and the results of clinical investigations in 74 patients with and 262 men without urethral Chlamydia (C.) trachomatis infection were evaluated: symptoms such as dysuria, discharge and/or burning/itching in the genital region were reported by 77% (n = 57) of the patients with an infection and 63.4% (n = 166) of the men without an infection. Upon clinical investigation, discharge was found in 55.4% (n = 41) of the chlamydia-positive patients and in 47.7% (n = 125) of the chlamydia-negative men. Only when yellow, whitish yellow and clear discharge were distinguished from one another was the difference between the two groups of patients (56.1% versus 12%) significant. Microscopic signs of urethritis, i.e. significant numbers of polymorphonuclear leukocytes (greater than 4 per high-power field and oil immersion) were detectable in the smears of 59.5% (n = 44) of the chlamydia-positive patients, in contrast to 15.6% (n = 41) in the smears of chlamydia-negative men. Overall, 67.6% (n = 50) of the patients with a C. trachomatis infection reported symptoms in the anamnesis combined with signs of urethritis upon clinical and microscopic investigation. There were 9.5% (n = 7) of the patients who either mentioned symptoms or showed clinical signs, and 13.5% (n = 10) who neither mentioned symptoms nor showed clinical signs. These results indicate that microbiological detection of the infectious agent is obligatory for diagnosis of urethral infection with C. trachomatis. PMID- 1938398 TI - [Treatment of venous ulcera cruris with dry wound dressings. Phase overlapping use of silver impregnated activated charcoal xerodressing]. AB - In a controlled randomized study on 40 patients with venous leg ulcers, monotherapy with a dry wound dressing (silver-impregnated--activated charcoal xerodressing; SIAX) was tested. The xerodressing was applied throughout the entire study and was compared with the conventional phase-adapted therapy using diverse topical modalities, e.g. as granulating ointments, zinc paste. etc. The parameters of wound healing were documented in the two randomized groups over 6 weeks and were statistically evaluated. In the statistical comparison of SIAX therapy (n = 19) and conventional therapy (n = 19) significant differences were found in favour of the SIAX group (increase of epithelialization, reduction of ulcer size; P less than 0.05). In addition, the ulcers of 6/19 patients (= 31.6%) treated with SIAX healed completely within the study period, in contrast to only 2/19 patients (= 10.5%) receiving conventional therapy. Exudate, granulation and colonization of the ulcers as well as odour, necroses, erythema and oedema of the surrounding areas were not significantly different. The study shows that a consistent therapy performed with dry wound dressings such as SIAX is superior to the conventional topical therapy of venous leg ulcers in some cases. Wound dressings provide new therapeutic modalities, being easy to apply and fully efficient, without side-effects. PMID- 1938399 TI - [Pigmented basalioma as pseudomelanoma of the breast]. AB - We report on a patient with a pigmented basal cell carcinoma of the nipple. Despite its rarity, it is important to know about this tumour because it is so easy to confuse it with malignant melanoma. PMID- 1938400 TI - [Ulcerating gout tophi. Surgical therapy in a patient with hyperuricemia, hyperlipidemia and alcohol abuse]. AB - We report on a 51-year-old male patient who had been suffering from gouty arthritis and podagra with relapsing attacks of severe pain for the last 10 years. We treated two tophaceus deposits on the left heel with the CO2 laser and conventional enucleating surgery. These tophi had immobilized the patient for months and it had not been possible to control them by conservative therapy. PMID- 1938402 TI - [Treatment and spontaneous regression of hirsutism]. PMID- 1938401 TI - [Pseudo-Kaposi sarcoma in Prader-Labhart-Willi syndrome]. AB - A 25-year-old male patient presenting with Prader-Labhart-Willi syndrome is reported. He had sought medical help because of lichenoid skin eruptions on his lower legs. Histologically the lesions turned out to be pseudo-Kaposi's sarcoma. The possible aetiopathologic relationship between the two primarily unassociated conditions is discussed. PMID- 1938403 TI - [Neurodermatitis and hospital stay]. PMID- 1938404 TI - [Eosinophilic granulocytes: on the way to knowledge of their functional significance]. AB - Although the eosinophilic granulocyte has been recognized as a blood cell type for more than 100 years, its functional significance has long remained an enigma. The introduction of successful isolation procedures resulted in rapidly progressive research efforts, but the concept of the functional role of this cell type made a full about turn between the 1970s and 1980s. In the 1970s, the role of the eosinophil was thought to be a homeostatic one, with its main task being to repair mast-cell-dependent tissue damage in parasitic and allergic disease. Further structural analysis and improved biological and clinical integration of such knowledge led to the completely revised concept of the 1980s: the eosinophil is now seen as the main culprit in the damage that accompanies allergic disease, as a result of mistaken identity between the parasite (where cytotoxic power against the aggressor is desirable) and the allergen (where the eosinophil's cytotoxic power results in self-damage). The latest research news about cytokine dependent regulatory mechanisms governing the eosinophilic reaction supports our hope that by specific blocking of tissue hormones, such as the lymphocyte-derived IL-5, elegant ways of manipulating hypereosinophilic reactions will be found in the near future. PMID- 1938406 TI - [The use of computer-assisted semen analysis (CASA) in the andrological laboratory]. AB - Computer-assisted systems for automated semen analysis have been developed to simplify the analysis of spermiograms and to eliminate the subjective influences of the investigator. Such systems are suitable for routine laboratory use only if their results correlate with the results of the conventional spermiogram evaluated by microscopy. We compared the sperm count and motility of 250 patients following analysis with the computer and the microscope. The values for sperm count and total motility evaluated by the computer and the microscope show close correlations, while those for linear and local motility are less closely correlated. The differences can be explained by methodological variations. In general, automated semen analysis appears to be a suitable alternative to the conventional method, even at this early stage of development. PMID- 1938405 TI - [Malignant melanoma in childhood and adolescence]. AB - In this review, the epidemiology and prognosis of malignant melanoma in childhood and adolescence (CMM) are discussed with reference to 627 patients reported in the literature. CMM accounts for only 1-2% of all melanomas, but there is the same increasing incidence as in adult melanoma. A distinction is made between congenital CMM (n = 27), CMM on giant congenital pigmented naevi (n = 69) and CMM in small pigmented lesions or de novo. The latter are identical in biological behaviour to melanomas in adults, while the CMM on giant naevi nearly always have an unfavourable outcome. Chemotherapy seems to be more effective in CMM than in adult melanomas, but prophylaxis is also the best therapy in children: early removal of congenital giant pigmented naevi and frequent monitoring, if not excision, of all congenital melanocytic lesions must be considered. PMID- 1938407 TI - [Locally infiltrative growth of squamous cell carcinoma of the skin and treatment guidelines resulting from it]. AB - The infiltrative growth behaviour of squamous cell of the skin carcinomas is characterized by subclinical outgrowths, very frequently extending horizontally and sometimes over long distances. They are presented in the form of a negative exponential function. These outgrowths have an irregular pattern. It is much more extensive in the case of tumours with a clinical diameter of more than 20 nm. All types of "blind" therapy such as cryopexy, irradiation, laser, and surgery monitored in only two dimensions involve an inevitable risk of recurrences, which can be calculated statistically from the results available. Routine histographical surgery of skin carcinomas in the form of continuous, 3 dimensional histology can dramatically reduce the risk of local relapse, especially in the case of small and medium-sized carcinomas. The test group presented here (411 carcinomas) was treated with histographic surgery using the paraffin section method; during the follow-up period (maximum: 7 years, minimum: 3 years) the danger of recurrence was 2.2% for all carcinomas but only 0.6% for those up to 20 mm in diameter (n = 340). Carcinomas with a diameter of more than 20 mm (n = 71) involved a much higher risk of recurrence with 9.8%. This is probably because of local micrometastases, which require more generous local excision with a safety margin of about 10 mm. PMID- 1938408 TI - [The significance of hot spots in psoriatic skeletal involvement]. AB - Bone scintigraphy is a modern method of low specificity but very high sensitivity in determining early changes in bone metabolism. There is a relationship between excessive skeletal metabolic disorders of the bone and the appearance of foci of maximum radionuclide uptake, or "hot spots". This distribution of radionuclide uptake has a specific character. In a retrospective study, we investigated the distribution of hot spots in 92 patients with various forms of psoriatic disease. Hot spots were found at and near to joints only. In enthesopathies hot spots are not found, because of lack of substance. They do, however, show signs suggesting a major disorder in collagen metabolism. Hot spots indicate a rather acute degree of skeletal involvement in psoriatic disease and are also frequently found in very active phases of psoriatic disease. Therapy-induced regression is possible. Spontaneous regression was observed only in the case of hot spots of short duration. The correlation of scintigraphic findings with X-rays shows that hot spots are signs of maximal focal metabolic activity. In a high percentage of cases they are leading up to a state of destruction, which can be shown on X-rays later. Among other parameters, they indicate the likelihood of skeletal involvement in psoriatic disease. Moreover, they indicate a high risk of "psoriatic arthritis". PMID- 1938409 TI - [Erythropoietic protoporphyria: synopsis of 20 patients]. AB - The authors present 20 patients (9 men, 11 women) with erythropoietic protoporphyria (EPP). The diagnosis was made on the basis of photosensitivity and porphyrin analysis. The disease first became apparent in the first years of life. The following acute symptoms were induced after exposure to sunlight: pruritus with or without skin changes, burning, pain and erythema, sometimes with petechiae, vesiculation and, in two cases, systemic symptoms. Chronic skin changes included hyalinosis cutis-like skin lesions, scarring, and also petechiae. Phototesting provoked only subjective symptoms, and none of the skin lesions characteristic of EPP could be induced. Postnatal diagnosis was attempted in three newborns, each of whom had one parent with proven EPP, by measuring the porphyrins in erythrocytes of cord blood. In all three normal porphyrin values were determined, and during an observation period of 3 years none has developed EPP. Therapy with carotenoids has yielded good to very good results in two-thirds of the patients. So far, a diagnosis of EPP has been established in 30 patients in Dusseldorf: one has died of liver cirrhosis and another has liver damage. PMID- 1938410 TI - [Lymphoepithelioma-like carcinoma of the skin]. AB - Lymphoepithelioma-like carcinoma of the skin (LECS) is a rare cutaneous tumour with histological features resembling those of Epstein-Barr virus-induced nasopharyngeal carcinoma. An LECS tumour may mimic lymphoid follicles in its composition. Its distinct histological pattern, however, is based on syncytial nests and cords of large pale-staining epithelial tumour cells surrounded by a dense lymphoplasmacytic infiltrate. Tumour cells show conspicuous vesicular nuclei with delicate chromatin and few prominent nucleoli. Histological differential diagnosis must include malignant lymphomas, Merkel cell tumour, squamous cell carcinoma and cutaneous metastasis of lymphoepithelioma. Immunostaining with anticytokeratin antibodies is highly significant in the differential diagnosis. Histological and immunohistological findings in an LECS removed from the upper lip of a 56-year-old women are reported. Serologic investigations did not indicate EBV-associated tumour growth. PMID- 1938411 TI - [Successful use of isotretinoin in type Zumbusch generalized pustular psoriasis following recovered etretinate-induced hepatitis]. AB - Administration of etretinate in a 29-year-old female patient suffering from severe pustular psoriasis caused a dramatic increase in liver enzymes. Liver biopsy revealed changes characteristic for drug-induced hepatitis. After normalization of liver parameters following withdrawal of etretinate, isotretinoin was administered during a severe pustular relapse. In contrast to etretinate, isotretinoin was well tolerated and resulted in a good therapeutic response. Thus, isotretinoin can be considered as an effective and safe therapeutic alternative for pustular psoriasis even after the occurrence of etretinate-induced hepatitis. PMID- 1938412 TI - [Acquired bilateral nevus of Ota]. AB - Two patients, a 53-year-old woman and a 73-year-old man, with a variety of a naevus of Ota (naevus fuscocoeruleus ophthalmomaxillaris) are described. In both cases, blue-brownish pigmentation appeared symmetrically on the skin of the head. Neither ocular involvement, nor nasal or oral pigmentation was found. Histological examination revealed melanin-bearing, spindle-shaped, or irregularly shaped melanocytes located exclusively in the upper dermis. PMID- 1938413 TI - [Necrobiosis lipoidica and Koebner phenomenon]. AB - Our report describes a 52-year-old female patient with bilateral foci of necrobiosis lipoidica in pretibial scars. The skin changes appeared 6 months after internal fixation of a tibial fracture in each case. PMID- 1938414 TI - [Systemic proliferating angioendotheliomatosis]. AB - A 75-year-old female patient with neurological disturbances and numerous erythematous skin infiltrates is presented. Angioendotheliomatosis proliferans systematisata was diagnosed on histological detection of intravascular tumour cells in the cutaneous blood vessels. On immunohistochemistry and electron microscopy, the mononuclear tumour cells were identified as atypical B lymphocytes. Our results provide further evidence that angioendotheliomatosis proliferans systematisata is a malignant angiotropic lymphoma with neurocutaneous manifestation. PMID- 1938415 TI - [Ozone layer and incidence of melanomas]. PMID- 1938416 TI - [Intraocular thrombosis caused by corticoid crystals in depot preparations]. PMID- 1938417 TI - [Borrelia burgdorferi infection. I. Aspects of basic research, current approach to diagnosis and therapy]. PMID- 1938419 TI - Stryker surgical microsurgical drills: activation by ground-referenced ESUs. PMID- 1938418 TI - Interpretive 12-lead electrocardiography. PMID- 1938420 TI - Datascope system 90 IABPs: suspension of catheter-related alarms. PMID- 1938421 TI - Home infusion therapy. PMID- 1938422 TI - Ambulatory infusion pumps. PMID- 1938423 TI - ECRI's software products and online services. PMID- 1938424 TI - Blade fracture of high-speed meniscus cutters during arthroscopic surgery. PMID- 1938425 TI - Thermal injuries and patient monitoring during MRI studies. PMID- 1938426 TI - [Union of the Swiss Associations of Surgical Specialties, 4th congress, Lucerne, 20-22 September 1990]. PMID- 1938427 TI - [Traumatic ruptures of the thoracic aorta]. AB - The authors present a group of 22 patients admitted for traumatic rupture of the thoracic aorta between 1969 and 1989. Most of them were polytraumatized patients (mean ISS 45). The majority of the injured patients possibly died before arriving at hospital. Amongst the other patients, there was a local tamponade of the hemorrhage. The risk of rupture of the patients arriving alive at the hospital is consequently restricted. The mortality of the patients operated in shock is high (3/4). The authors recommend to operate these lesions in delayed emergency. PMID- 1938428 TI - [Modified dynamic hip screw implant in pathologic fracture of the femoral neck (juvenile bone cyst)]. AB - Pathological fractures of the neck of the femur during adolescence should be treated in order to maintain the original length of the femoral neck. The available implants are designed as sliding nail plates and therefore are not capable of blocking collapse of the neck in the presence of a cystic lesion. By loading the unthreaded part of the Dynamic Hip Screw by segments of tubes the gliding mechanism is locked. The hip screw modified in this way can secure anatomic healing of the femoral neck. PMID- 1938429 TI - [Possibilities for treating chronic radius head dislocations]. AB - Thirteen patients with neglected luxation of the proximal radius who were treated with different surgical procedures at the Orthopaedic Department of the Kantonsspital in St. Gallen (Switzerland) returned for evaluation at an average of 7 years postoperatively. The luxation was traumatic in 11 cases (7 Monteggia fractures) and in 2 cases due to a dysplasia of the forearm. In 7 patients the deformity recurred and in 1 a synostosis between radius and ulna was noticed. In 4 cases the wrist showed a relative overlength of the ulna. Proximal osteotomy of the ulna in combination with open reduction of the proximal radius gave better results than the other procedures. Congenital luxation of the proximal radius does not cause much symptoms but surgical treatment often results in recurrence of the deformity. Therefore, we only occasionally advocate operative therapy in these cases. PMID- 1938430 TI - [Dorso-lumbar spinal compression fractures in the child. Follow-up at the termination of development]. AB - Between 1970 and 1985, we count 32 children with compressive fractures of the vertebral column. None of them undergo a surgical procedure. We examine 24 of these 32 children with a mean delay of 10.5 years. Most of the fractures were referring to sporting activities and home games. The main localization was dorsal (T6) and upper-lumbar (12). The mean reduced height of the ventral portion of the vertebra was 27%. Some 10 years later, two third of the patients have some persistent pains and half of them daily. Most of the aches concerned children of more than 12 years when trauma occurred and those who developed a scoliosis during evolution. Wonder the global static of the rachis is little concerned in most of these children. Therefore compressive vertebral fracture of the youngster should be reduced and fixed by a corset. But the immobilization shouldn't be longer than 2 months, accompanied by appropriate gymnastics and followed by a quick renewal of the sporting activities. PMID- 1938431 TI - [Resorbable implants in craniofacial surgery in childhood. A contribution to the development of poly(lactide) implants]. AB - After research on minipigs we use since 2 1/2 years our polylactid and polydixanon implants for stabilisation after osteoplastic trepanation and in craniofacial reconstructions. The presented set with headless screws and nuts and woven bands are described in detail. Biodegradable osteosynthesis was done in 15 patients aged 11 months to 17 years and two months (m: 6 years four months). The results are at least as well as with conventional steel implants (plates, screws and wires). We did not see infections in any instant, and no patient had a second operation for explantation of fixation devices. After this encouraging prospective trial we are going to simplify the construction as well as the implantation procedure and to enlarge the spectrum of indications by using plates. PMID- 1938432 TI - [Various possibilities of reconstruction of the thoracic wall in radiation defects]. AB - Reconstruction of the thoracic wall is often necessary after cancer surgery of the breast or irradiation. The resulting large defects often cause an instable thoracic wall. To reconstruct stability, we can use fascia or dura mater. The large defects can be closed either by latissimus flap, or, if the thoracodorsal artery is destroyed, which is often the case by rotating flaps according to the technique of Schrudde or Bohmert, in very rare cases by distant flaps from the neighbouring upper arm. PMID- 1938433 TI - [Sonographic acute and follow-up diagnosis after blunt abdominal trauma]. AB - Experience with ultrasonographic acute and follow-up diagnostic as noninvasive imaging procedure for blunt abdominal trauma was analysed in a retrospective study. Between 1986 and 1989 166 organ lesions were noticed in 440 patients with clinically regarded diagnosis of a blunt abdominal trauma. 107 patients were laparotomised. Retrospectively, the sensitivity concerning free fluid in the abdominal cavity caused by lesion of an intrabdominal organ was 0.96 and the specifity 0.98. The predictive value of a positive test was 0.91 and the predictive value of a negative test was 0.99. The rate of negative laparotomy was 1.3%. Thus the sole use of ultrasonographic diagnostic and the non-use of peritoneal lavage seems justified in case of blunt abdominal trauma. Some figures illustrate typical cases and our own results. PMID- 1938434 TI - [Technical aspects of spleen saving therapy in splenic trauma]. AB - The haematological and immunological consequences of splenectomy have been the subject of increasingly intensive studies over the last few years. As a result there has been a significant change in the management of splenic trauma with the emphasis on organ preservation which has been associated with a possible reduction in postoperative infectious complications. The safety of splenic preservation (splenorrhaphy) has been demonstrated. There has also been a change in the increased use of non-surgical (conservative) management of injuries in adults, a policy which previously was reserved for children. There is no difference in the postoperative bleeding rate between patients with splenectomies or patients with splenorrhaphies. Non-surgical treatment is in adults not yet established. In our department splenic preservation gets an increasing weight in our treatment policy, even in patients with multiple injuries. Our treatment policy initially classifies the splenic injury into one of five groups and this determines the subsequent operative procedures. The crucial part of the surgical technique in splenic preservation involves the immediate dissection and delivery of the spleen from its subdiaphragmatic position, thus avoiding iatrogenic injuries which can readily occur in the emergency situation. The hilus is then clamped with a non-crushing vascular or intestinal clamp, which avoids blood loss during the repair. The methods used for the repair depend on the grade of the injury. Means to prevent sutures cutting through the tissue (resorbable collagen platelets, resorbable gauze, teflon stripes) and a variety of methods to achieve haemostasis (infra red photocoagulation, haemostatic material and supportive mesh) are used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938435 TI - [Splitting liver transplantation. Orthotopic liver transplantation in two recipients with a single donor liver]. AB - Surgical reduction of donor livers to treat small children has been performed successfully in several centers. While this procedure improves the allocation of livers, it does not increase the organ supply. Since either lobe can be used in preparing a reduced-size graft, both lobes can become grafts, if acceptable vascular pedicles and bile ducts can be established for each one. We report and demonstrate a technique, in which a donor liver has been split and was used to transplant in two recipients. PMID- 1938436 TI - [Gallbladder morphology after extracorporeal shockwave lithotripsy of gallstones with the MPL-9000]. AB - The effects of extracorporeal spark-gap shockwave lithotripsy (ESWL) on human gallbladder-morphology are barely known. We studied the gallbladders of nine patients cholecystectomized 5 to 166 days after ESWL. Patients were treated one to three times receiving a mean of 1928 +/- 693 shockwaves per treatment, with a total of 3375 +/- 1307 per patient. Control gallbladders were of randomly selected patients after plain cholecystectomy (age and sex-matched). There was no difference in pathomorphology of the two groups. No signs of trauma related damage (hemorrhage, necrosis, ulceration, scar, or hemosiderin deposits) other than from surgical manipulation were found. Predominant pathomorphological changes were signs of chronic cholecystitis due to gallstone disease. In conclusion, spark-gap ESWL did not induce deleterious morphological damage to the gallbladder, although large numbers of shock waves were applied. PMID- 1938437 TI - [Preservation of donor livers with University of Wisconsin solution]. AB - The University of Wisconsin-solution extends the cold storage time of liver grafts over 20 hours. The early function is equal or better than with Eurocollins solution. Due to the extended preservation time, logistical advantages are present. However, deliberate extension of cold ischemia over the limit of 20 to 24 hours seems not yet indicated, since primary non-functioning grafts have a higher incidence after extended preservation. PMID- 1938438 TI - [Postoperative monitoring of transplanted kidneys using color Doppler sonography]. AB - In 52 renal transplant patients a prospective study was carried out to compare the validity of szintigraphy and color-duplex-sonography for demonstrating the renal blood flow. In 49 cases the questions bout intra-allograft blood flow could be answered. In two cases szintigraphy was unable to make a right evidence. Angiodynography is a non invasive method to demonstrate the blood flow in renal allografts and is able to replace the szintigraphy. PMID- 1938439 TI - [Anticoagulants and psoas hematoma]. AB - Between 1985 and 1989, 16 patients under anticoagulant therapy developed a haematoma in the psoas or iliac muscle, 60% of them with a severe femoral nerve entrapment syndrome. Six patients were operated, all with a femoral nerve paralysis, and 5 of them had a quick and complete recovery. Only one still has some complaints in the femoral nerve territory. Among the 10 patients with a nonoperative approach, none of those with a femoral nerve paralysis was completely cured at 6 months. The surgical treatment is the best way to a quick recovery, provided it is done at an early stage. PMID- 1938440 TI - [New therapeutic approach in the celiac trunk compression syndrome]. AB - Etiology and treatment of the coeliac compression syndrome remains controversial. The external compression, near the origin of the truncus coeliacus and the poststenotic dilatation is well demonstrated by angiography on a lateral projection. The development of collaterals like the pancreaticoduodenal and gastroduodenal artery can be assessed on a frontal view. The grading of the stenosis as well as the direction of the flow in these artery can be measured with the duplex sonography. These investigations show a steal syndrome: blood coming from the mesenteric artery irrigate the common hepatic artery through the collaterals. The flow in the common hepatic artery is therefore retrograde. We used an original technique to correct this flow pattern in the case of a 52-year old patient: after dividing the arcuate ligament, we reduced the vascular territory of the truncus coeliacus with the proximal ligation of the splenic artery. The duplex sonography shows postoperatively the suppression of the steal syndrome with a normal flow pattern in the hepatic artery despite minimal change in the stenosis of the truncus coeliacus. The patient remained asymptomatic since the operation. We concluded that an angioplasty or reimplantation of the truncus coeliacus is unnecessary to correct the steal syndrome. A normal flow can be provided by a stenotic truncus coeliacus once the splenic artery has been ligated. PMID- 1938441 TI - [Femoropopliteal venous bypass in distal duplication of the great saphenous vein with bridge veins. Case report]. AB - A 74-year-old patient with peripheral arterial obstructive disease II B presented a full-length obstruction of the superficial femoral artery and additionally a segmental 10 cm long obstruction of the deep femoral artery. The arteries of the calf were patent. In this situation a bypass with an autologous vein was taken in advice. At surgery in December 1988 the great saphenous vein from the contralateral leg was prepared. It was found to be duplicated and contained numerous bridging veins. The duplication was maintained to compensate for the difference of calibre. The proximal anastomosis was done with the double-lumen graft including in between a split bridging vein. This arrangement provided favourable anatomic and functional outlets to the two saphenous branches. At follow-up in January 1990 the patient was fully reintegrated and had an unlimited walking distance. Doppler sonography showed normal closing pressure in the peripheral arteries. The intravenous digitalized subtraction angiography demonstrated regular perfusion of both branches of the duplicate bypass. PMID- 1938442 TI - [Loss of the extremity despite patent vascular reconstruction]. AB - This retrospective study concerns 8 patients, who had successful vascular reconstruction for ischaemia of a lower extremity but nevertheless needed lower or upper leg amputation. The analysis shows that in four patients (one of them diabetic) misjudgement was the cause of failure. The other four patients all had diabetic angiopathy. No misjudgement or wrong decision was found in the analysis of their case. Here the failure is interpreted as the fatal destiny of a seriously damaged microangiopathic extremity. PMID- 1938443 TI - [Myocutaneous latissimus dorsi sliding flap in reconstruction of the lower thoracic wall in chronic fistula caused by cystic echinococcosis of the liver]. AB - We report the successful treatment of a 47-year-old man who had a 22-year history of chronic discharge from a hepatic echinococcal cyst. Before treatment in our unit there had been 8 previous attempts to control the fistula. By means of a right thoracoabdominal incision (with resection of the 7th and 8th ribs) it was possible to perform a cystectomy with subsequent marsupialisation of the residual cyst wall to the skin. However, after 2 weeks subsequent treatment with maximal Albendazol therapy there was still a big persistent cavity which required further debridement. This resulted in resolution of the infection and allowed a definitive closure of the big cavity and the thoracoabdominal wall using a myocutaneous latissimus dorsi flap. The patient's subsequent course has been uneventful with no recurrence of the fistula. PMID- 1938444 TI - [Reconstructive methods of the antero-lateral thoracic wall after extensive surgery of invasive tumors]. AB - Local recurrence after conservative or enlarged surgery for breast carcinoma, or primary chest wall's tumors should first be approached surgically, chimio- and radiotherapy being used only later on. A precise local and general evaluation has to be made first, trying to determine whether there is or not an invasion of bony structures. When they are free of tumor, regional transfer of musculocutaneous flaps can usually cover the defect (latissimus dorsi, 1-2 rectus abdomini, pectoralis major); great omentum is used when this defect is too large. When ribs, sternum or deep structures are invaded, reconstruction uses successively: a mersilene mesh, bone cement, an omental flap covered with mesh skin grafts 2 days later. Surgical management of these difficult situations is most of the time only a palliative measure which gives these patients a better quality of life for the short time they still have got. PMID- 1938445 TI - [The role of a new method for occlusion of fistula tracts]. AB - Digestive fistulae have a quite variable clinical presentation, depending on their origin and topography. Even when very small, they can cause considerable mechanical or metabolic derangement. Surgical correction often implies an operation with important consequences. The injection of an occlusive emulsion can, in a certain number of cases, close off the fistulous tract with minimal inconvenience. We have injected several invalidating fistulae between the digestive or respiratory tract and the skin with Ethibloc. Total occlusion of the fistulae was accomplished after one or more injections. The emulsion is resorbed after around 10 days, leaving a scar. The inclusion of radio-opaque material allows intraoperative control of injection. This technique widens the therapeutic modalities applicable to a difficult medical condition. When confronted with advanced inflammatory or neoplastic disease, for example, Ethnibloc injection can be considered if the tissue quality is sufficient. Gross infection or tissue necrosis are, in our experience, relative contraindications; the occlusive emulsion cannot adhere and is rapidly evacuated by the fistula. PMID- 1938446 TI - [Urinary catheterization: transurethral or suprapubic approach?]. AB - 75 patients, needing a bladder drainage for nonurological indications and having sterile urines were studied after randomization into two groups. In the first group, drained with an urethral catheter, urinary infection took place in 12 (= 30%) patients, while it was detected in 4 (= 11%) drained with a suprapubic catheter. In this latter group, patients felt more comfortable, had less pain; the duration of urinary drainage and hospital stay was shorter. PMID- 1938447 TI - [Bassini or Shouldice operation?]. AB - Between October 1988 and March 1990 a controlled, prospective study was conducted comparing the operative methods of Bassini and Shouldice for hernia repair. On 100 patients (11 female, 89 male) the Shouldice-technique was used, on 55 patients (6 female, 49 male) the Bassini-technique. Most patients were operated under local anesthesia. No significant difference was noted between the two groups regarding the postoperative complication rate (hematoma, wound infection). However, patients had a shorter hospital stay after the Shouldice operation. Six patients (10.9%) had recurrent hernia after the Bassini procedure, one patient (1%) after the Shouldice procedure. An increased risk for recurrent disease was found in patients with the Bassini operation who already had recurrent hernia. Because of the significant shorter hospital stay and the significant lower incidence of recurrent hernia, we abandoned the operative method of Bassini in favour of the Shouldice procedure. PMID- 1938448 TI - [Surgical indications, choice of procedure and results in upper gastrointestinal hemorrhage]. AB - Even today acute upper gastrointestinal bleeding carries a high mortality rate. To improve results it is important to define and operate on those patients in whom recurrent bleeding is expected. Whenever possible early elective surgery is recommended. To improve long-term results we propose definitive ulcer surgery even in patients presenting as emergencies. Implementation of this policy does not increase operative mortality. PMID- 1938449 TI - [Transarticular amputation at the knee in peripheral arterial occlusive disease. Very positive experiences after routine use of the Klaes and Eigler technique]. AB - In a retrospective study we compare our experience with the through-knee amputation in peripheral vascular disease. In the first 15 patients we used an amputation technique with circular incision. In about 50% of these patients we observed a delayed wound healing or they needed a reamputation to a higher bony level. In the 17 following patients we used the amputation technique described by Klaes and Eigler, using a posterior myocutaneous flap to cover the condyles. Only one of these patients needed a reamputation and another had a secondary wound healing. We conclude that the technique of through-knee amputation described by Klaes and Eigler is better adapted for patients with peripheral vascular disease. PMID- 1938450 TI - [Meniscus sonography. Analysis of results of a prospective study of 191 patients]. AB - During the time of May 1989 until May 1990, 191 patients with clinically suspected meniscus lesions were sonographically examined. An arthroscopy was carried out on 49 patients, where this suspicion was found to be true. There was an accuracy of 78%. Through observations of wrong negative findings (22%), morphological changes were observed, of these, the real available sonographical findings were misinterpreted. PMID- 1938451 TI - [Helicopter and emergency physician at the accident site. Medical comparison between altitude and flat land emergency care]. AB - In-field intensive care reduces lethality and morbidity in severe trauma. We analyze and compare 400 medical helicopter rescue flights in the region of Basel and 325 medical air-rescues in the mountains of Interlaken. The presence of a physician in the helicopter is based on an interventional concept, with clinical diagnosis, monitoring and early intensive in-field care. Compared to the mountains, we find a predominance of road accidents (44%) in the region of Basel, with more head injuries (47.3%) and more polytrauma (19.4%) and thoraxtrauma (20.5%). In the mountains, with a majority of sport accidents (65.5%), pelvis and extremity injuries (73.4%) prevailed. As a consequence of inaccessible accident sites in the mountains, 23% of the rescues had to be performed by winch. An endotracheal intubation was performed in 35.5% of the patients in the Basel region, and in 11.6% in the mountains. Fixation of fractures and hemostasis was performed in both regions in 22% and 12% of the cases. In spite of high rates of severe conditions in both regions (57% in Basel, 17% in the mountains), the low mortality prior to and during air transport (2.5% in the Basel and 2.7% in the Interlaken region) confirms the necessity of the concept of early in-field intensive therapy. This concept allows good analgesia, is save and comfortable for the patients. The presence of a physician in the air rescue team has to be recommended not only for rescues in the plain, but also in the mountains. PMID- 1938452 TI - [Rumania January 1990: acute medical deficits and chronic shortage--an evaluation at the site]. AB - Between January 4 and 8, 1990, a medical delegation of the University Hospital Zurich (three surgeons, one OT-nurse) was sent to Bukarest. They escorted a large sending of surgical and pharmacological equipment. The assignment was 1. to evaluate the situation in the hospitals around the Bukarest area; 2. to determine the feasibility and the need of medical emergency support; 3. to assess the usefulness and practicability of medium-term relief. A total of 11 hospitals were visited in Bukarest, Pitesti, Racovita and Schitu-Golesti. It was found that 1. a sufficient number of doctors and medical personnel is available; 2. emergency aid is important regarding pharmaceuticals (local anesthetics, analgetics, insulin), infusions, dressing material, surgical instruments and external fixation equipment; 3. medium-term support is need for the complete medical equipment (syringes, injection and infusion sets, probes, suture material, etc.). Local medical literature and journals are worthless. Doctors long for high-quality medical books and periodicals. We can help! PMID- 1938453 TI - [Amputations of the lower extremity]. PMID- 1938454 TI - [The role of emergency endoscopy in acute lower intestinal hemorrhage]. AB - The diagnostic procedures performed in patients with acute lower intestinal haemorrhage were analyzed retrospectively. During a three year period 35 patients with acute rectal bleeding were admitted and these patients underwent altogether 79 endoscopies, 7 visceral angiographies and 7 labeled red cell scintigraphies. The bleeding source was identified by endoscopy in 31 (89%) patients and remained undetermined in 4 (11%). The most common lesions responsible for the bleeding were diverticula, ischemic colonopathy and tumors. Despite the clinical impression of lower GI-tract haemorrhage 4 patients (11%) bled from the upper GI tract. We conclude that emergency gastroscopy and colonoscopy, performed in the intensive care unit, are the procedures of choice for the investigation of the patient with acute lower GI-tract bleeding. PMID- 1938455 TI - [Gastrointestinal hemorrhage of rare origin]. PMID- 1938456 TI - [Surgical vascular anatomy of the thoracic wall]. AB - Since the rediscovery of the latissimus dorsi flap in 1976 axial skin- and musculocutaneous flaps have dramatically improved the possibilities of plastic reconstruction. Better knowledge of the microvascular anatomy of the thoracic wall is the condition for safe flap surgery. The frequent topographic variations and the possibility of a reversed flow through vascular anastomosis are shown. This paper is ment to be a basic introduction to the following communications on flaptechniques in the same journal. PMID- 1938457 TI - [Imaging procedures in the evaluation of tumors of the thoracic wall]. AB - Modern sectional imaging methods supplement the clinical examination of chest wall tumors ideally by demonstrating their deeper components and relation to neighbouring structures. Imaging methods are still limited in demonstrating detail anatomy, a disadvantage that is caused by limited soft tissue contrast and motion artifacts. In certain cases, a specific diagnosis is made by the specific behaviour of the tissue, whereas much more often morphological criteria and the topographic location and relation of the tumor help get the specific diagnosis. Image-guided percutaneous biopsy of the chest wall is an easy, relatively non invasive way of getting the definitive diagnosis. PMID- 1938458 TI - [Thoracic fascio-cutaneous flap]. AB - Fascio-cutaneous flaps (LFC) of the thoracic wall are of rather historical interest with the exception of axillary and lateral thoraco-dorsal LFC. The reason has been the development of muscular, musculo-cutaneous and microvascular flaps which provide larger surfaces for defect cover, greater arc of rotation or none at all as well as superior vascularisation. The axillary LFC is used to correct axillary contractures after burns or to cover skin defects following radical excision for hidradenitis suppurativa. The lateral thoraco-dorsal LFC permits immediate reconstruction of an amputated breast with a minimum of time and blood loss and an unsurpassed fiability. Furthermore it allows postoperative X-ray treatment if necessary as well as uninhibited control of loco-regional metastases. PMID- 1938459 TI - [Gastroduodenal hemorrhage: endoscopic treatment]. PMID- 1938460 TI - [The unstable thoracic wall: possibilities for treatment]. AB - In the treatment of severe chest injuries with flail chest either positive pressure mechanical ventilation (and tracheostomy) is necessary or the surgical stabilisation of the chest wall by osteosyntheses of the broken ribs. Fourteen patients (age 27-73) with severe chest injuries and paradoxical respiration were operated and the rib fractures stabilized by means of small reconstruction plates and cerclage wires. Three patients died due to other reasons. There were no serious complications. The results are reported. In severe chest injuries surgical treatment seems to be justified; it reduces the need of artificial respiration and can be recommended. PMID- 1938461 TI - [Prosthetic material in thoracic wall reconstruction]. AB - For closing a big defect of the chest well the use of prosthetic material can be considered if there is not enough viable tissue of sufficient strength and size available. This synthetic material should be strong, stable, flexibel and inert, and it should be integrated in the body's own tissue. A mersilene netting fulfils these criteria. For covering the netting the greater omentum is preferred for its many valuable properties. The technique and the application of this combined network plasty is described. PMID- 1938462 TI - [Breast cancer: temporal evolution of loco-regional recurrence treated by omentoplasty. A study of 49 cases]. PMID- 1938463 TI - [The infected sternotomy]. AB - In the presence of a wound infection following a sternotomy, an active surgical treatment is currently the method of choice. Large debridement followed by an effective wound closure is advised by most authors. In our experience, most cases will respond to this treatment whateither flap is used: omentum, rectus abdominis, latissimus dorsi, pectoralis major musculocutaneous flaps. However, a few patients have had repeated attempt to close the sternal defect without success. In these cases a proper surgical treatment is a life-saving procedure. Thorough debridement and closure with bipedicled pectoralis major and rectus fascio-cutaneous flaps with drainage of the mediastinum is advised. Stabilisation of thoracic wall and filling of the dead space are not mandatory. PMID- 1938464 TI - [Rectum resection with colo-anal anastomosis and formation of a colonic J pouch in deep rectal cancer]. AB - Sphincter-saving operations are now generally accepted for the treatment of mid rectal cancers. Different techniques have been described: low colorectal anastomosis with staplers, pull-through procedures and coloanal anastomosis. The functional results following these procedures are impaired by loss of the reservoir function of the rectum. To avoid frequency and urgency a J-shaped colonic reservoir is constructed and anastomosed to the anal canal. We are presenting our first four cases using this technique. All patients are personally reviewed 19-29 months after the operation. In correspondence with the literature all our patients had a good functional result with good continence and only one bowel movement per day. We conclude the creation of a neorectum makes the functional result of a coloanal anastomosis more predicable. PMID- 1938465 TI - Patterns of intestinal metaplasia in gastric biopsies. A comparison of different histochemical classifications. AB - A total of 217 cases of gastric intestinal metaplasia (IM), out of 491 cases of consecutive multiple gastric biopsies, were examined using various histochemical methods. Three classifications were adopted (1) Jass and Filipe's (1979), (2) Segura and Montero's (1983), and (3) our own distinguishing two types of small intestine IM (incomplete and complete) and two types of colonic IM (incomplete and complete). Our classification revealed (1) a group of 'pure' IM cases (44%), (2) a group of 'combined' IM cases (15%), either small intestinal or colonic, expressing a maturating line, and (3) a conspicuous group of mixed 'mosaic' IM cases (41%) consisting of all possible combinations between the basic IM types. No significant correlations were found between each IM type and associated diseases (i.e. gastritis, stump gastritis, ulcer, adenoma and adenocarcinoma). However, a suggestive association between colonic IM and malignancy was observed. Our results confirmed the heterogeneity of IM and indicated two differentiation cell lines (ileal and colonic), thus providing additional evidence of impaired maturation and aberrant differentiation along various cell lines, supporting Leblond's (1976) unifying theory on the origin of intestinal epithelial cells. PMID- 1938466 TI - A simple method for ultrastructural enzyme cytochemistry on small volumes and numbers of isolated cells. AB - A simple technique is described for ultrastructural enzyme cytochemistry using small volumes and numbers of single cells. Small aliquots (1-5 microliters) of single cells suspended in a glutaraldehyde fixative are incubated on poly-L lysine-coated glass coverslips. Cells in contact with the coated coverslip become immobilized to that support. All changes of solutions are accomplished without repeated centrifugation. PMID- 1938467 TI - Monoclonal antibodies to rat renal tissue: an approach to the immunohistological analysis of the nephron-collecting duct system, and ultra-structural localization of antigens. AB - To obtain more accurate information on the nephron-collecting duct system, monoclonal antibodies against renal tissue were prepared. BALB/c mice were immunized every two weeks with rat renal tissue, either cortex or medulla. Spleen cells were collected and fused with myeloma cells sensitive to hypoxanthine aminopterin-thymidine medium. Hybrids were selected for production of antibodies by indirect immunofluorescence and cloned by the limiting dilution method. Tissue reactivity of the antibodies obtained was defined by immunofluorescence. The intracellular localization of antigenic determinants was ascertained by immunoelectron microscopy. The antibodies were classified into four major groups: (1) antibodies against proximal tubules; (2) antibodies against distal tubules and the loop of Henle; (3) antibodies against collecting duct system; and (4) antibodies against glomeruli. Using immunoelectron microscopy, various intracellular antigenic determinants were recognized, such as brush border, apical canaliculi, vacuolar apparatus, luminal and basolateral plasma membranes. The results obtained indicated that electron microscopy is indispensable for the immunohistological study of the nephron-collecting duct system. The observations help to understand morphological and functional diversity of the nephron collecting duct system. PMID- 1938468 TI - Immunohistochemical characterization of purple acid phosphatase-containing leucocytes in the human placenta. AB - A tartrate-resistant acid phosphatase activity was detected in the human placenta. This enzyme displayed immunological properties similar to those of the group of purple acid phosphatases that can be demonstrated with a rabbit polyclonal antibody against bovine spleen purple acid phosphatase. The placental enzyme was mainly localized immunohistochemically to neutrophil granulocytes of the maternal blood between the placental villi and within foetal capillaries using the bovine spleen antibody and the commercial monoclonal antibody M1 directed against an antigen found on mature granulocytes. A minor activity was detected in decidual cells and the syncytiotrophoblast. The presence of purple acid phosphatase in placental granulocytes may be related to special immunological conditions of pregnancy. PMID- 1938469 TI - Ontogenic expression of histo-blood group antigens in the intestines of suckling pigs: lectin histochemical and immunohistochemical analysis. AB - The expression of intestinal histo-blood group AO and related antigens was investigated in piglets during an 8 week suckling period. Lectin histochemical and immunohistochemical analyses were undertaken on sections of resin-embedded intestinal tissue and semi-quantitative scoring systems were adopted for categories of lectins and monoclonal antibodies reactive with carbohydrate moieties present in core, backbone and terminal oligosaccharide sequences of histo-blood group antigens. Distinct age-related changes were observed in the terminal glycosylation of both secretory and membrane glycoconjugates. Histo blood group A antigen was identified in intestinal mucin 5 weeks after birth and the precursor H antigen was found in goblet cells at week 1. H antigen was undetectable on intestinal membranes during the first 3 weeks of suckling but a conspicuous and sustained level of this form of fucosylation was apparent during the latter half of the suckling period. More complex membrane glycosylation involving further fucosylation and/or the expression of A antigen, was evident in the latter part of the suckling period. These temporal changes in membrane and secretory glycosylation may be physiologically important during intestinal adaptation and development in young pigs. PMID- 1938470 TI - The influence of lactation products on the temporal expression of histo-blood group antigens in the intestines of suckling pigs: lectin histochemical and immunohistochemical analysis. AB - Lectins and carbohydrate-specific monoclonal antibodies were used as cytochemical probes to investigate the possible influence of lactation products on the expression of intestinal membrane and secretory glycoconjugates in suckling piglets. Two different lactational regimes were compared; the first involved normal rearing of piglets for 8 weeks on a single dam and the second involved repeated cross-fostering of littermates onto recently farrowed sows, thereby restricting them to early milk. Five histo-blood group phenotypes were recognized within the piglet population: two immature phenotypes, 'O immature' or 'Oi' and 'A immature' or 'Ai', and three mature forms, 'O', 'A' and '-'. Under the normal suckling regime the transition from immature to mature OA phenotypes was evident at the fifth week post partum. However, in the repeatedly cross-fostered piglets this transition was evident much earlier at 3 weeks post partum. It is suggested that qualitative or quantitative variations in milk composition during the sow's lactation may significantly influence the expression of intestinal histo-blood group antigens in her suckling young. PMID- 1938471 TI - Primary extracellular ceroid type lipopigment. A histochemical and ultrastructural study. AB - An extracellular ceroid-type (ECC) lipopigment which appears histologically as wavy hyaline membranes or, less frequently, as an amorphous solid or broadly reticulated mass is described. Its ultrastructure is either amorphous or membranous and consists either of simple linear membrane-like aggregates or elaborated trilaminar membranes. The histochemical profile is, as in histiocytic intracellular ceroid, dominated by autofluorescence, strong hydrophobicity, acid and extraction resistance. Staining for aromatic acid residues and periodic acid Schiff positivity are strong but variable. Lectin receptors are either absent or sparse. The pigment is found solely within the lipid rich tissue debris, bound to processes marked by necrosis of adipose or steatosed tissues and interpreted as originating de novo extracellularly from liquid unsaturated lipids under the influence of local enzymatic and nonenzymatic lipid oxidation catalysts. A hitherto unknown form of extracellular ceroid is the so-called membranocystic lesion found in Nasu-Hakola's disease, in several other conditions and in annular ceroid in human atheromas. PMID- 1938472 TI - Secretory pathway of vitellogenesis in the liver of the cockerel as revealed by immuno-gold and computer-assisted digitization techniques. AB - The protein A-gold immunocytochemical technique was used to localize the secretory pathway of oestradiol-induced vitellogenin in hepatic parenchymal cells of the cockerel. Liver was removed from experimental birds on the 1st, 4th and 8th day following oestradiol-treatment, and embedded in Lowicryl K4M resin cured at -20 degrees C. In selected electron micrographs the fractional surface area of each of the intracellular compartments was measured by the computer-assisted digitization technique. Labelling was detected over the cisternae of the rough endoplasmic reticulum (RER), the Golgi apparatus, the immature secretory vacuoles (ISV) including condensing vacuoles and the mature secretory vacuoles (MSV). Counts of the gold particles demonstrated an increasing concentration which progressed in the order RER less than Golgi less than ISV less than MSV and identified the secretory pathway of the protein. The highest density of labelling was obtained on the 4th day, when vitellogenin reaches its peak activity. Autophagic activity (or crinophagy) was also found in lysosomes and its labelling intensity increased daily. A hypothesis concerning the secretory pathway of non stored proteins by the liver is discussed further. PMID- 1938473 TI - Postembedding immunogold histochemistry for the localization of laminin and its E4 and P1 fragments in mouse kidney embedded in LR-White and LR-Gold. AB - A method is presented which permits the ultrastructural localization of laminin and its E4 and P1 subunits in the renal cortex of the mouse embedded in LR-White or LR-Gold. It was performed with postembedding immunogold histochemistry using polyclonal antibodies against either the entire laminin molecular or the E4 fragment or with a monoclonal antibody against the P1 fragment. Localization of laminin was achieved in LR-White and in LR-Gold embedded kidney. Using polyclonal antibodies against the entire laminin molecule, laminin could be localized with direct as well as with indirect immunogold histochemistry with a gold labelled IgG as secondary antibody. In contrast, immunostaining for the E4 or the P1 fragments was possible only with antibodies directly labelled with gold. PMID- 1938474 TI - Immunohistochemical localization of bone sialoprotein in foetal porcine bone tissues: comparisons with secreted phosphoprotein 1 (SPP-1, osteopontin) and SPARC (osteonectin). AB - Bone sialoprotein (BSP) is a prominent component of bone tissues that is expressed by differentiated osteoblastic cells. Affinity-purified antibodies to BSP were prepared and used in combination with biotin-conjugated peroxidase labeled second antibodies to demonstrate the distribution of this protein in sections of demineralized foetal porcine tibia and calvarial bone. Staining for BSP was observed in the matrix of mineralized bone and also in the mineralized cartilage and associated cells of the epiphysis, but was not observed in the hypertrophic zone nor in any of the soft tissues including the periosteum. In comparison, SPP-1 (osteopontin) and SPARC (osteonectin), which are also major proteins in porcine bone, were observed in the cartilage as well as in the mineralized bone matrix. In addition, SPARC was also present in soft connective tissues. Although SPP-1 distribution was more restricted than SPARC, hypertrophic chondrocytes, periosteal cells and some stromal cells in the bone marrow spaces were stained in addition to osteoblastic cells. The variations in the distribution and cellular expression of BSP, SPARC and SPP-1 in bone and mineralizing cartilage indicate these proteins perform different functions in the formation and remodelling of mineralized connective tissues. PMID- 1938475 TI - How selective are the 'selective periodate oxidation' methods used in sialic acid histochemistry? PMID- 1938476 TI - Expression of a dystrophin-related protein associated with the skeletal muscle cell membrane. AB - We previously reported that a protein which has immunological cross-reactivity with and a molecular weight similar to dystrophin, the Duchenne muscular dystrophy (DMD) gene product, is expressed on the muscle cell membrane (Tanaka et al. 1989b). To examine if this is the translation product of the autosomal transcript with homology to dystrophin mRNA identified by Love et al. (1989), we raised an antibody (PDRP) against a synthetic peptide corresponding to the putative protein (DRP) and examined its expression and cellular localization in human and murine skeletal muscle samples. In immunoblotting, PDRP stained a band with a similar molecular weight to dystrophin in samples from DMD and Becker muscular dystrophy (BMD) patients and control (non-DMD/BMD) human. PDRP was expected not to cross-react with dystrophin because the antigenic peptide was not homologous to dystrophin. In fact, PDRP did not cross-react with dystrophin present in a BMD patient. Immunohistochemically, PDRP stained the muscle cell membrane in samples from DMB and BMD patients and from mdx mice. Only a slight staining was observed in muscles from control human and wild type mice. Our results confirm the presence of DRP in human and murine skeletal muscles, and further demonstrate that it is localized on the cell membrane. The abundance of DRP in dystrophin deficient muscles might be related to some compensatory mechanisms. PMID- 1938477 TI - Immunocytochemical localization of synapsin I in the adrenal medulla of rats. AB - The localization of synapsin I in the rat adrenal medulla was studied using the light- and electronmicroscopic immunohistochemistry. By light microscopy, many dot-like reaction products for synapsin I were recognized to be distributed throughout the medullary tissue. The immunoelectron microscopy clearly revealed that gold particles for synapsin I accumulated in abundance in the nerve terminals forming synapses with the chromaffin cell, while the particles were not localized in the chromaffin cells at all. In the nerve terminal, the gold particles were localized exclusively in the region occupied by synaptic vesicles except for the region just beneath the presynaptic plasma membrane. The synaptic vesicles were frequently linked with the adjacent ones by filamentous structures implicated in synapsin I. It is concluded morphologically that synapsin I is a highly-specific protein for the genuine neuron, and is not detected even in the chromaffin cell which originates from the neural crest. PMID- 1938478 TI - Morphological evidence for the association of plasma membrane glycoprotein IIb/IIIa with the membrane skeleton in human platelets. AB - We examined the association between glycoprotein (GP) IIb/IIIa, a receptor for fibrinogen, and membrane skeletons in both unstimulated and thrombin-activated human platelets. After a treatment with dithiobis succinimidyl propionate (DTSP), a cross-linker, unstimulated and activated platelets were simultaneously extracted and fixed with a fixing solution containing Triton X-100. Also, the localization of GPIIb/IIIa on the plasma membrane was observed by a preembedding staining method of unextracted platelets. In unstimulated platelets, 20-40% of the whole plasma membrane remained in the detergent-extracted samples. Amorphous structures with 10-70 nm in diameters are distributed at 20 to 100-nm intervals on the surface of plasma membrane. Similar structures also were identified in the intact platelets by the immunocytochemical method. By careful inspection, we found that most of the amorphous structures that contained gold particles were connected to the submembrane zone just beneath the plasma membrane. The submembrane zone was identified as the membrane skeleton because actin was detected in the zone. After activation, detergent-insoluble granules were surrounded by dense networks of microfilaments in the central part of platelets. The filaments were identified as actin and became associated with myosin. These results demonstrate that GPIIb/IIIa on the plasma membrane is connected to the membrane skeleton and suggest that, during activation, actin filaments which extend into the cytoplasm from the membrane skeleton increase and form dense networks around Triton-insoluble granules. PMID- 1938479 TI - Immunoelectron microscopic demonstration of estrogen receptors in osteogenic cells of Japanese quail. AB - The localization of estrogen receptors (ERs) in osteogenic cells was immunoelectron microscopically examined in the femurs of female and estrogen treated male Japanese quail. An electron dense reaction product showing ER localization was observed in the nuclei of osteoblasts and immature osteocytes in the medullary bone of the female quail. However, reaction product was not seen in the osteoclasts. On the endosteal bone surface of male quail, nuclear reaction product was detected in bone lining cells. After 24 h of estrogen treatment, reaction product was observed in the nuclei of preosteoblasts on the endosteal bone surface. After 48 h, the medullary bone partly appeared along the endosteal surface. Nuclear reaction product was seen in osteoblasts on the medullary bone surface. PMID- 1938480 TI - Production and immunocytochemical application of a highly sensitive and specific monoclonal antibody against rat dopamine-beta-hydroxylase. AB - A highly sensitive and specific monoclonal antibody against the enzyme dopamine beta-hydroxylase (DBH) from rat was produced and coded DBH 41. The generated hybridoma secreted immunoglobulins of mouse IgG1 subtype, as determined by radial immunodiffusion. This antibody, characterized by immunoblotting against a crude rat DBH preparation, was found to specifically recognize two bands of molecular weight 70 and 75 kDa corresponding to the soluble and membrane bound forms of the enzyme, respectively. With regard to species specificity, the anti-DBH antibody recognizes only the rat DBH molecule as it exhibits no cross-reactivity with either mouse, human, rabbit, guinea pig, cat or bovine DBH. Comparative immunocytochemical localization of DBH and TOH immunoreactivity was performed in different brain regions and we found that the DBH 41 antibody specifically stained DBH-containing neurons and fibers in the rat central nervous system (CNS). The high sensitivity of the DBH 41 antibody permitted us to detect immunologically the presence of the enzyme even in areas where only scattered DBH containing fibers were present. PMID- 1938481 TI - Association between nuclear matrix and terminal transferase: an electron microscope immunocytochemical analysis. AB - Nuclear matrix extracted from KM-3, a human pre-B leukemia cell line, appears to have a site of linkage for terminal deoxynucleotidyl transferase (TdT). The immunocytochemical analysis of the distribution of TdT using a rabbit polyclonal antibody which recognizes human terminal transferase, shows that the nuclear framework of these cells contains sites of immunoreactivity that appear uniformly distributed on the matrix fibres, while the nucleolar region is unreactive. This evidence points out the possibility that TdT could reside in the proteinaceous scaffold of the nucleus defined as nuclear matrix, thus strengthening the evidence for the metabolic and regulatory roles ascribed to this nuclear framework. PMID- 1938482 TI - Expression of epidermal growth factor in the rat kidney. An immunocytochemical and in situ hybridization study. AB - The renal localization and the site of synthesis of epidermal growth factor (EGF) were investigated in the rat kidney by immunohistochemistry and in situ hybridization techniques. EGF was localized in the cells of the thick ascending limb of Henle (TAL) and distal convoluted tubule (DCT). At the ultrastructural level, EGF immunoreactivity was distributed on the apical membrane and trans Golgi complex of the TAL and DCT cells. These segments of the rat nephron also hybridized to prepro-EGF cRNA probes in a specific manner, indicating that TAL and DCT are the sites of EGF synthesis in the rat kidney. PMID- 1938483 TI - Immunocytochemical localization of albumin, transferrin, angiotensinogen and kininogens during the initial stages of the rat liver differentiation. AB - Rat albumin, transferrin, angiotensinogen, T kininogen (TKg) and high molecular weight kininogen (HKg) gene expression was examined immunocytochemically in embryonic and fetal livers. All these plasmatic proteins, angiotensinogen excepted, are detected as early as day 11 of gestation in intestine epithelial cells and embryonic hepatocytes. Angiotensinogen becomes expressible only at day 13 of gestation. During the early fetal period, the protein immunostaining increases strikingly in parallel with the hepatocyte differentiation. Albumin and transferrin are highly expressed comparatively to kininogens and angiotensinogen. For the first time, specific HKg is demonstrated in the rat liver. PMID- 1938484 TI - Flow cytometric measurement of rRNA levels detected by fluorescent in situ hybridization in differentiating K-562 cells. AB - The flow cytometric detection of fluorescent in situ hybridization (FISH) performed on intact cells in suspension is a recently described method (Bauman et al. 1989). We studied the application of this method for monitoring cellular differentiation. The amount of rRNA which is taken for a good indicator of growth in size, the rate of protein synthesis and the G0 G1 transition was followed by FISH. For this purpose biotinylated single stranded RNA probes obtained by transcription from a 2.1 kb BglII-EcoRI fragment of the human 28S ribosomal RNA gene subcloned into plasmid pGEM2 were used. K-562 leukaemic cells, used as targets, were induced to differentiate by dimethyl sulfoxide, phorbol myristate acetate and hemin. In the last two cases the cell cycle analysis, growth kinetics, cellular morphology and immunophenotyping indicated differentiation into monocytic and erythroid direction, respectively. The differentiation was accompanied by a rapid increase followed by a decrease to the base level of rRNA. This was not observed in the uninduced exponentially growing control cells. Based on our results, we propose that the FC-FISH detection of the rRNA level is a valuable method to distinguish between cell subpopulations. We propose that using other probes, FC-FISH will become useful to monitor different cellular processes. PMID- 1938485 TI - Cytometric analysis of DNA replication inhibited by emetine and cyclosporin A. AB - DNA staining methods based on aspecific interactions with dye molecules have been replaced by an immunofluorescent approach to measure DNA replication. Biotin-11 dUTP was incorporated into permeable thymocytes isolated after emetine or cyclosporin A treatment of mice. Active sites of DNA replication were amplified based on biotin-avidin interaction and verified under fluorescent microscope. Cytometry of fluorescent images allow the direct measurement of replicating DNA without aspecific detection of total cellular DNA. Cytometric analysis of replication revealed that emetine acts at the early S phase, while cyclosporin A blocks in vivo DNA synthesis at mid S phase. PMID- 1938486 TI - Induction of raf-1 protein immunoreactivity in guinea pig hippocampal slices during the in vitro maintenance. AB - The cellular raf-1 protooncogene encodes a cytoplasmic serine/threonine protein kinase; raf-1 is expressed not only in tumour cells, but also in normal brain tissue. However, the substrate of raf-1 kinase is unknown and its function is still hypothetical. In cell cultures, mitogen stimulation may alter its properties, including its kinase activity and subcellular distribution. The aims of the present study were: (1) light- and electron microscopic immunohistochemical localization of raf-1 kinase in hippocampal slices; (2) the follow-up of the possible changes in localization and detectability during the in vitro maintenance and low-frequency stimulation. Our results suggested the induction of neuronal raf-1 kinase during the in vitro maintenance. The possibilities of increased transcription and enzyme activation are discussed. PMID- 1938487 TI - [Applied cytology in the differential diagnosis of rhinitis]. AB - The pathogenesis of acute and chronic diseases of the nasal mucosa is multivariate. Cytological examination of nasal cells by conventional and immunocytochemical techniques helps to clarify the diagnosis. We present the morphology and functions of cell populations of interest, as well as typical cytological findings and their interpretation. Allergic and pseudoallergic disease can be recognised and differentiated from other forms of rhinitis. The demonstration of IgE-positive cells represents a new diagnostic feature of high sensitivity and specificity. In addition to the pathogenesis of the disease, cytology also indicates the degree and appropriate therapy of rhinitis. PMID- 1938488 TI - [Endoral sonography in comparison with transcutaneous sonography, computerized tomography and magnetic resonance tomography]. AB - Endoral ultrasound was introduced for imaging of T1 and T2 tumors of the anterior third of the tongue and the floor of the mouth in 1988. Using this method, 100 patients with diseases of the oral cavity and the oropharynx were examined, and the findings were compared with those of transcutaneous ultrasound, CT and MRI. Endoral ultrasound provided valuable additional information in tumors of the tongue base and the middle and dorsal third of the tongue. Tumors of the tonsil were demonstrated very well. MRI proved to be superior for imaging of large lesions. CT was of less value in diagnostic imaging of the oral cavity and the oropharynx due to low soft tissue contrast. PMID- 1938489 TI - [The status of sequential chemo-/radiotherapy in inoperable head and neck cancers. Personal results and review of the literature]. AB - Between March 1986 and October 1987 75 patients with advanced cancer of the head and neck were treated with initial chemotherapy before surgery and/or radiotherapy. Chemotherapy consisted of three courses of cisplatin or carboplatin combined with 5-fluorouracil (5-FU). Three weeks after the last course of chemotherapy 34 patients with unresectable tumours received conventional fractionated radiotherapy (60-64 Gy). Of these 34 patients, 32 were evaluated for response and survival with a minimal follow-up of 3 years (22% stage III, 78% stage IV). As the response to cisplatin/5-FU and carboplatin/5-FU was similar (72% versus 64%), survival rates of both chemotherapeutic regimens are presented together. At the end of sequential chemo-radiotherapy 11 patients (34%) were clinically free of disease with an overall response rate of 69%. The survival after 3 years was 12.5% (4 patients) with a median of 15 months. Disease-free survival was 27% (3/11). These poor results confirm the results of other investigators. They indicate that induction chemotherapy does not improve the results of conventional radiotherapy in unresectable carcinomas of the head and neck, even when using highly effective platinum-containing regimens. PMID- 1938490 TI - [Artificial nutrition with nasogastric catheters. Experiences with a new administration system]. AB - Enteral nutrition via a nasogastric tube is widely used but is inconvenient for patients: the nostril and skin of the nose become irritated and ulcerated, and the tube causes pain and psychological trauma. We have developed a new system which combines the security and ease of nasogastric tube feeding with comfort for the patient. The distal part of the tube is invisibly anchored in the vestibule of the nose, using a special device. The outer part is attached only when feeding is necessary. We report 52 ENT patients who have used this system. PMID- 1938491 TI - [Small papular tumors of the perifollicular and perivascular connective tissue of the head and neck area]. AB - The clinical picture of perifollicular benign tumors resemble that of juvenile warts, but the histopathology is completely different. Three different forms of perifollicular tumors, pure or mixed, have been observed. We report a fourth, previously unrecorded form, named perivascular fibroma from its histological appearance. The histological findings indicate a possible inflammatory etiology, as is also suggested by perifollicular fibroma, whereas postinflammatory signs are absent in trichodiscoma and fibrofolliculoma. The prognosis after removal of these tumors is favorable. PMID- 1938492 TI - [Parotidectomy: functional and esthetic results]. AB - We report a retrospective study of 154 patients after parotidectomy. The patients were examined immediately and on average about 40 months after the operation. The emphasis of the examination was to assess both functional as well as aesthetic results. The function of the facial nerve was evaluated by Stennert's score. We found a median score of 20% 3.3 days after operation. The late postoperative results (34.3 months after operation) indicated that 91% of the patients had no paresis. There was no significant difference between superficial parotidectomy and total parotidectomy in regard to the aesthetic result. The decision for partial or total parotidectomy should be based exclusively on pathological and oncological considerations. PMID- 1938493 TI - [15 years experience with secondary septorhinoplasty]. AB - Every surgeon performing septorhinoplasty has complications and must do secondary corrections. The author describes those complications and secondary corrections which he encountered during the last 15 years. Explanations for the mishaps are offered, and successful corrective measures are described. PMID- 1938494 TI - [Endonasal, endoscopic-microscopic control of the decompression of the optic nerve. An anatomic endoscopic presentation of the operation]. AB - The indication for decompression of the optic nerve after indirect trauma is made both by the ophthalmologist and the ENT-surgeon. The ENT-surgeon usually reaches and decompresses the optic canal by a transethmoidal-transsphenoidal route. The majority of authors prefer the transfacial approach to the ethmoid including resection of the crossing plane comprising the frontal process of the maxilla, the ethmoid, the lacrimal and the frontal bone. Hitherto we have knowledge of only one author utilising an endonasal approach to decompress the optic nerve. At the university hospital of Gottingen, the ENT-surgeons gathered experience with the endonasal, endoscopically and microscopically controlled operation method, which is less traumatic to the patient and avoids postoperative mucoceles of the frontal sinus. This surgical procedure is described by surgical-anatomical specimens. PMID- 1938495 TI - [Correlation between nasal polyposis and perennial allergy exemplified by house dust mite and house dust allergy]. AB - A total of 139 patients with nasal polyps were investigated by a standardized history, intradermal skin test and nasal challenge to house dust mite allergy. The aim of the study was to assess the disputed role of perennial allergy in patients with nasal polyps using allergens to the house dust mite as an example. Using our diagnostic criteria we found allergy to house dust mite in 28% of all cases. We found this diagnosis in 44.8% of patients aged 10-39. We recommend, especially in this age group, an allergy test, if necessary with the appropriate therapy. Test correlations are illustrated in 174 patients who have been examined by the above methods. Good reproducibility was found by the nasal challenge, which led to the right diagnosis in 92%, compared with 81% by a standardized history. Therefore, it can be considered to be the key to the diagnosis of allergy. PMID- 1938496 TI - [Inner ear deafness following lumbar puncture. A complication requiring patient education?]. AB - Deafness after lumbar puncture has been reported occasionally. Until now this complication has been regarded as spontaneously reversible, but a more recent publication of three cases of irreversible hearing loss possibly caused by lumbar puncture casts doubt on this. It has been proposed that this complication should be included in the pre-operative information given to patients, but we oppose this proposal. PMID- 1938497 TI - [DNA cytometric studies of cholesteatoma of the middle ear]. AB - Thirteen smears of middle ear cholesteatomas were investigated by the recently developed interactive DNA cytometry. The demonstration of DNA aneuploidy in 9 of the 13 cholesteatomas possibly indicates that these lesions are neoplasms. PMID- 1938498 TI - [Aberrant course of an internal carotid artery through the middle ear. Case report and review of the literature]. AB - We report right-sided mixed deafness with objective pulsating tinnitus and a circumscribed bluish-red bulging discoloration of the ear drum in a 8 year old girl caused by a transtympanic course of the internal carotid artery. The diagnosis was established by clinical examination, impedance audiometry and CT scans, and was confirmed by angiography. PMID- 1938499 TI - Osteopathic principles and practices: maintaining a vital link in osteopathic education. PMID- 1938500 TI - Two toddlers may have been infected with the human immunodeficiency virus (HIV) after playing with an HIV-tainted syringe. PMID- 1938501 TI - Three organ transplant recipients died of the acquired immunodeficiency syndrome (AIDS) PMID- 1938502 TI - Children and cholesterol: what is a physician to do? PMID- 1938503 TI - Health fair glaucoma screening: follow-up evaluation. AB - Glaucoma screening is a standard procedure at many health fairs. Information on correct screening techniques, instrumentation, and target populations has been available. However, a scarcity of information exists concerning the success of efforts to follow up on abnormal results. This study reports on the findings of a long-term (6-month) follow-up of all individuals with abnormal tonometric results screened at an inner-city osteopathic hospital. Of the 218 subjects screened, 15 were found to have abnormal tonometric results. Seven of the 15 subjects were actually reached at the 6-month follow-up interval. Four of the seven had not sought any further eye care; two had sought nonmedical evaluation; only one had sought medical ocular care, and that subject was later found to have glaucoma. The results presented in this article indicate that compliance by this population is inadequate. Inner-city participants require more education. We encourage physicians to promptly refer such patients for appropriate medical ocular care. PMID- 1938504 TI - Pentoxifylline as adjunctive therapy in leg ulcer management. AB - Refractory or recurring leg ulcers typically signify the presence of impaired venous or arterial microcirculation (or both). A current hypothesis suggests that local oxygen and nutrient deficits occur because capillary lumens narrow and become permeable to fibrinogen and proteins by activated white blood cells and inadequate fibrinolysis. As a result, the deposition of a relatively impermeable perivascular fibrin sheath occurs, preventing adequate delivery of oxygen and nutrients. Therapy should therefore aim at reversing these deficits and improving wound healing. Pentoxifylline (Trental), used in combination with local wound care and appropriate antibiotic therapy, has been successful in significantly improving the healing of refractory leg ulcers. Pentoxifylline can reverse the abnormal function of white and red blood cells and platelets, as well as reduce blood viscosity and vascular permeability. The mechanisms of action of pentoxifylline are described in light of current hypotheses pertaining to leg ulcer development. Also discussed are nine cases in which pentoxifylline, when added to previously unsuccessful local wound care, either improved or healed the refractory ulcers. PMID- 1938505 TI - Flow cytometry: a diagnostic aid. AB - Flow cytometry can provide the clinician with a wealth of information on a given disease entity. It uses fluorescence and laser technology, thereby allowing characterization of a host of cell parameters and functions. Flow cytometry can be used to diagnose and prognose immunologic, infectious, and malignant disease, with minimal invasiveness. Any material within the reach of an aspiration needle is amenable to cytometric analysis. A qualified pathologist, well-trained technologist, and well-informed clinician all play crucial roles in the appropriate application of cytometric analysis of the clinical specimen. The wide variety of applications make flow cytometry a useful tool for all clinicians, regardless of practice location. PMID- 1938506 TI - Atypical measles: a diagnostic conundrum. AB - Atypical measles syndrome has been reported extensively in the pediatric medical literature. However, the clinical picture in the adult is similar to that of many other diseases, making the diagnosis elusive. The case reported here was unusually morbid. The patient, a young man, had been in excellent health until the onset of a perplexing syndrome. When seen by the author, he had been ill for 1 week with chills, pharyngitis, and vomiting; later, a nonpruritic, maculopapular rash developed. Symptoms progressed to pneumonitis and hepatitis. A rubeola titer was obtained and was found to be considerably elevated. Because of the high titer and the fact that the patient had been immunized against measles in early childhood, the diagnosis was atypical measles syndrome. Two theories are offered to explain the pathogenesis of this disease. PMID- 1938507 TI - Gastric adenocarcinoma associated with human immunodeficiency virus (HIV) infection. AB - Gastric adenocarcinoma developed in a 33-year-old homosexual man with human immunodeficiency virus (HIV) infection. This type of cancer is very rare in a man of his young age and in the absence of other factors. The tumor was aggressive and led to rapid death. Whereas Kaposi's sarcoma and lymphomas have been associated with HIV, there are only a few documented cases of adenocarcinoma associated with a suppressed immune system. The association between HIV infection and the virulence of this tumor appears to be strong. PMID- 1938508 TI - Epidermoid anal cancer: treatment by radiation alone or by radiation and 5 fluorouracil with and without mitomycin C. AB - One hundred ninety-two patients with primary epidermoid cancer of the anal canal were treated by a series of prospectively designed, sequential non-randomized protocols of radiation alone (RT), radiation with concurrent 5-Fluorouracil and Mitomycin C (FUMIR), or radiation with concurrent 5-Fluorouracil only (FUR). The 5-year cause-specific survival rates were 69% overall, 68% RT, 76% FUMIR, 64% FUR. The primary tumor was controlled by radiation with or without chemotherapy in 68% (130/191) overall, 56% (32/57) by RT, 86% (59/69) by FUMIR, 60% (39/65) by FUR. The results with FUMIR were significantly better than with either RT alone or FUR, and except in tumors up to 2 cm in size, this superiority was found in all T stages. Regional lymph node metastases were controlled in 33 of 38 (87%) overall. The finding of clinically detectable regional lymph node metastases at presentation did not affect survival significantly in any treatment group. Anorectal function was preserved in 88% of the patients in whom the primary tumor was controlled, and in 64% overall. The delivery of 5FU and MMC concurrently with uninterrupted radical irradiation, 50 Gy in 20 fractions in 4 weeks, produced severe acute and late normal tissue morbidity. Split course treatment, and reduction of the daily fractional dose to 2 Gy, diminished the severity of normal tissue damage. Omission of Mitomycin C reduced acute hematological toxicity, but was associated with a decreased primary tumor control rate. The most effective treatment protocols as measured by survival rates, primary anal tumor control rates, and the likelihood of conservation of anorectal function included the administration of both Mitomycin C and 5-Fluorouracil concurrently with radiation therapy. PMID- 1938509 TI - Preoperative irradiation for cancer of the rectum with extrarectal fixation. AB - Tumor mobility of rectal cancer is well known to have prognostic significance for operative resection, local recurrence, and survival. Between 1976-1988, 220 patients have been consecutively treated with high dose preoperative radiotherapy at Thomas Jefferson University Hospital. During this time period, 134 patients were clinically determined by the surgeon and radiotherapist to have extrarectal tumor fixation as a primary indication for preoperative irradiation and are the subject of this review. The patient population can be further divided into two subgroups which include 49 patients with clinical tethering/partial fixation, and 85 patients with completely fixed tumors. Patients were treated with 4-field pelvic radiotherapy to 45 Gy in 25 fractions. Depending on location and degree of fixation, a localized boost dose was frequently delivered to the tumor for an additional 4.8-9.6 Gy using opposed high-energy lateral fields. Surgical resection was instituted 4-6 weeks post completion of radiotherapy. Significant tumor regression permitted sphincter preserving surgery in 105/134 (78%) of these patients. With a median follow-up of 37 months, the overall 5-year actuarial survival for our postradiation Stage A/B1 patients was 92% (n = 28), and 63% for Stage B2/C patients (n = 91). Local recurrence occurred in only 7% of the Stage A/B1 patients, and 18% in the Stage B2/C patients. Analyzed by pre-treatment clinical evaluation, the 5-year actuarial survival of these patients was 68% and 60% in the clinically tethered and fixed tumor subgroups, respectively (p = .51). Pelvic control was demonstrated in 86% of the patients in the tethered subgroup, and in 80% of the preoperative fixed patients. The combined treatment was well tolerated, with complications limited to 6% of the patient population. We conclude that preoperative radiotherapy for rectal carcinomas with clinical extrarectal fixation provides optimal presurgical cytoreduction and excellent survival. Furthermore, sphincter function can be maintained in a majority of patients with appropriate attention to patient selection. PMID- 1938510 TI - High-dose-rate intraluminal brachytherapy (HDRIBT) for esophageal cancer. AB - High-dose-rate intraluminal brachytherapy (HDRIBT) for patients with esophageal cancer has been performed with and without external radiotherapy (ERT) in our department since May 1980. From May 1980 through December 1986, 92 patients with esophageal squamous cell carcinoma were treated with HDRIBT following ERT. These patients were divided into a limited disease (LD) group and an extensive disease (ED) group. Complete response and partial response rates after treatment were 48% and 38% in the LD group, and 9% and 65% in the ED group, respectively. The median survival time and 2-year survival rate was 13 months and 39% in the LD group, and 8.5 months and 7% in the ED group, respectively. The 5-year survival was 17% in the LD group. HDRIBT without ERT was used to treat six patients with small, superficial esophageal squamous cell carcinoma from August 1987 through July 1988. No patients were candidates for surgery because of coexisting medical problems. Each patient received 6 Gy per treatment, twice weekly with a total of 24 Gy; five of the six patients were treated on an outpatient basis. The tumor had disappeared completely in all six patients at the time of first follow-up endoscopic study less than 1 month after treatment, and no local recurrence had occurred after 11 to 22 months in five of the six patients. Five of the six patients were alive after 11 to 22 months, and one died with mediastinal metastasis at 15 months. PMID- 1938511 TI - Adjuvant therapy of resected adenocarcinoma of the pancreas. AB - Seventy-two patients underwent resections of pancreatic carcinomas between 1981 and 1989 at the Hospital of the University of Pennsylvania and were evaluable for follow-up. There were three treatment groups as treatment policies evolved. Initially, patients were observed after surgery without adjuvant treatment (Group 1-33 patients). Beginning in 1984, patients were offered adjuvant radiation therapy postoperatively (Group 2-19 patients) and eight of these patients also received 5-FU as an IV bolus on the first 3 days of the first and fifth weeks of treatment. Twenty patients were treated with chemosensitized radiation therapy following surgery using 96-hour 5-FU infusions during the first and fifth weeks of treatment. There were four postoperative deaths, which are excluded from the analysis, and sites of failure could not be determined for five other patients. Among evaluable patients, local recurrences occurred in 85% of the patients in group 1, 55% of the patients in group 2, and 25% of the patients in group 3. The 2-year survival was 35% in group 1, 30% in group 2, and 43% in group 3. Patients with involved surgical margins had a poor survival; only 2 of these 16 patients survived longer than 18 months. Among patients with negative margins, the 2-year survival is 41% in group 1, 33% in group 2, and 59% in group 3. Although the number of patients is smaller, the 3-year survival is 22% in group 1, 11% in group 2, and 47% in group 3. Chemosensitized irradiation is well tolerated in these patients. The major challenge in this group of patients is nutritional maintenance. There was no other significant toxicity. The trend in these observations suggests that survival following pancreatic resection is substantially improved with the addition of adjuvant chemosensitized radiation therapy. PMID- 1938512 TI - Adjuvant therapy with hepatic irradiation plus fluorouracil in colon carcinoma. The Gastrointestinal Tumor Study Group. AB - In an attempt to reduce disease recurrence after curative resection of transmural or node positive colon cancer, the Gastrointestinal Tumor Study Group performed a randomized trial of observation versus 5-FU plus 2100 cGy to the liver. A total of 300 eligible trial participants form the basis of this report. Significant toxicity after the combination caused major dose reduction from the original course of 500 mg/m2 to 350 mg/m2. No therapeutic benefits were noted in either survival or recurrence endpoints; the liver recurrence rate was not decreased by the therapy. Analysis of patients with transmural colonic involvement and negative nodes, one to four positive, and greater than four positive nodes indicates that not all patients are alike with respect to disease outcome or overall survival, and that node number is an important determinant of patient selection for adjuvant trials. PMID- 1938513 TI - The impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity in early-stage Hodgkin's disease. AB - A retrospective analysis of patients with supradiaphragmatic Stage I-II Hodgkin's disease was performed to assess the impact of pelvic recurrence and elective pelvic irradiation on survival and treatment morbidity. One hundred twenty patients were treated with radiotherapy (RT) alone; 38 received total nodal (including pelvic) irradiation (TNI), 63 received modified total nodal (excluding pelvic) irradiation (MTNI), and 19 received involved-field or mantle irradiation only (less than MTNI). Thirty-three patients received combined-modality therapy. In laparotomy-staged (PS) patients treated with RT alone, the overall treatment failure rate was 13% after TNI, 24% after MTNI, and 43% after less than MTNI. The pelvic failure rate in PS patients was 0% after TNI, 9% after MTNI, and 29% after less than MTNI. Cause-specific deaths in patients treated with RT alone occurred in 10% following less than MTNI, 13% following MTNI, and 10% following TNI. Cause specific deaths due to pelvic failure in patients treated with RT alone occurred in 5% following IF and 6% following MTNI, and also occurred in 7% of patients receiving combined-modality therapy. The potential disadvantages of elective pelvic irradiation in early-stage Hodgkin's disease include compromise of future tolerance of chemotherapy in the event of treatment failure, and infertility. Gonadal function was assessed in 67 patients less than 35 years old at the time of treatment. Compromise of gonadal function was correlated with the lack of special testicular shielding during pelvic irradiation and chemotherapy in the male, and with no oophoropexy before pelvic irradiation in the female. Twelve of 26 patients with recurrence after either less than MTNI or MTNI, with or without chemotherapy, were alive and without evidence of disease at greater than 2 years after completing salvage therapy, compared with 7 of 11 patients with recurrence after TNI. PMID- 1938514 TI - Low-dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern. AB - The treatment of Non-Hodgkin's lymphomas with follicular growth pattern and advanced stage of disease remains controversial. Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated. The EORTC Lymphoma Cooperative Group has performed a randomized prospective trial comparing short duration low dose total body irradiation (TBI) vs combination chemotherapy (CHVmP) + consolidation radiotherapy. Ninety-three patients were entered; of 84 evaluable patients, 44 received TBI and 40 CHVmP. Complete remission (CR) rates were 36%--TBI and 55%--CHVmP, but overall response rates were identical, 76 versus 69%. No significant difference in freedom from progression or survival was observed. No unexpected toxicity was seen. Although numbers are small, we cannot conclude that aggressive combination chemo radiotherapy resulted in a better survival. Our analysis confirms that there is a constant risk of relapse. Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population. PMID- 1938515 TI - Influence of dose rate on local control of breast carcinoma treated by external beam irradiation plus iridium 192 implant. AB - From 1971 to 1983, 20 T1, 267 T2, and 53 T3 biopsy-proven adenocarcinomas of breast were definitively managed by radiotherapy. The breast and regional nodes received 45 Gy of 60Co irradiation in 25 fractions over 5 weeks (45 Gy/25/5 wks). Electrons were used to deliver a further 15 Gy/7/1.5 weeks to the internal mammary chain and 25 Gy/11/2.5 weeks to the lower axilla. The primary tumor was boosted by Iridium 192 implant for a further 37 Gy prescribed at 85% of the basal dose rate (Paris system). Rigid needles were secured by templates in single plane (58/398) or double plane (340/398) geometry. Results of the 340 two-plane implants have been analyzed to look for a possible influence of dose rate on local control. Follow-up for patients free of local recurrence is 4-204 months (median: 92 months). The 340 tumors were divided into three groups according to dose rate: 0.32-0.49 Gy/hr (n = 95), 0.50-0.59 Gy/hr (n = 120), and 0.60-0.90 Gy/hr (n = 125). The three groups are statistically comparable according to age, tumor size, mean 60Co dose, mean Iridium dose, overall treatment time, and follow up. The local failure rate in the three groups is 27% (26/95), 20% (24/120), and 13% (16/125) (p less than 0.03, Chi square). At 15 years the estimated local control (Kaplan Meier) is 60%, 72%, and 84% (p less than 0.02, Logrank), respectively. This analysis indicates that there is a significant effect of dose rate on local control for carcinoma of the breast treated by combined external beam (45 Gy) plus Iridium 192 implantation (37 Gy). To maximize local control the authors recommend an implant dose rate of greater than or equal to 0.6 Gy/hr. PMID- 1938516 TI - Radiotherapy in T1 laryngeal cancer: prognostic factors for locoregional control and survival, uni- and multivariate analysis. AB - From 1975 through 1985, 194 patients with T1 glottic, 37 patients with T1 supraglottic, and 3 patients with T1 subglottic cancer were treated with radiotherapy. Local control and ultimate locoregional control (after salvage surgery) was 91% and 97% for T1 glottic, 84% and 81% for T1 supraglottic, and 2/3 and 3/3, respectively for subglottic tumors. In uni- and multivariate analysis local control for glottic tumors was associated with extension of the tumor on the vocal cord (entire length of vocal cord vs others, p = 0.01) and continuation of smoking after therapy (yes/no, p = 0.03). No prognostic factor for local control was found in supraglottic tumors. However, regional control and survival were impaired by N stage (N0 vs N+, p less than 0.0005), local recurrence (yes/no, p less than 0.0005), and extension of the tumor (one supraglottic subsite vs more than one, p less than 0.05). Mild late complications were seen in 13% of patients without salvage therapy. Following univariate analysis, field size, fraction size (greater than 2 Gy), maximum tumor dose (greater than 70 Gy), age, post-treatment biopsy, and tumor site were associated with complication rate. Following multivariate analysis, site, fraction size, maximum tumor dose, and continuation of smoking after therapy were independent prognostic factors for mild late complications (mostly arytenoid edema). PMID- 1938517 TI - Changes in TCD50 as a measure of clonogen doubling time in irradiated and unirradiated tumors. AB - Dose-cure experiments have been carried out on a moderately well differentiated murine mammary carcinoma, designated MCA-4, at different stages of growth after tumor-cell inoculation or after 8 mm established tumors had been exposed to 60 Gy. TCD50 assays were performed at 1, 3, 7, 14, or 21 days after tumor cell inoculation, or when tumors reached a size of 6 or 8 mm. Likewise, TCD50 assays were performed at 0.25, 1, 3, 5, 8, 12, 16, or 21 days after 8 mm tumors had been exposed to a 60 Gy priming dose, or when the recurrent tumors reached 6 or 8 mm. All irradiations were performed under hypoxic conditions. The TCD50 (95% confidence limits) was 64.0 (61.7-68.3) Gy for the 6-mm and 71.9 (70.1-73.9) Gy for the 8 mm tumors, and these values were unaffected by preirradiation. Direct analysis was used for the simultaneous estimation of D0, clonogen number, and clonogen doubling time from the pooled data. There was no significant difference between D0 estimates for the preirradiated and control tumors, and the pooled estimate was 10.6 (9.6-11.8) Gy for tumors assayed at specified time points where the size was unknown. This is clearly higher than in tumors of known size [estimate for 6- and 8-mm tumors: D0 = 5.4 (4.5-6.6) Gy] owing to size and other heterogeneity. The clonogen doubling times (Tclon) were 3.4 (3.0-4.0) days in the preirradiated tumors and 5.8 (4.9-7.1) days in the unirradiated tumors. It is not unreasonable to assume that the systematic error due to heterogeneity was approximately the same for D0 and Tclon (since variable clonogen number is likely the predominant source of heterogeneity), and thus the ratio of D0 for tumors of unknown sizes (10.6 Gy) and D0 for tumors of known sizes (5.4 Gy) can be used to "correct" the Tclon estimates, with the result that Tclon (preirradiated) = 1.7 days and Tclon (unirradiated) = 3.0 days. We conclude that the clonogen doubling time was shorter in tumors exposed to a single high-dose irradiation than in unirradiated controls, which implies the existence of faster cell repopulation in irradiated tumors. PMID- 1938518 TI - The v-abl, c-fms, or v-myc oncogene induces gamma radiation resistance of hematopoietic progenitor cell line 32d cl 3 at clinical low dose rate. AB - A variety of viral and cellular oncogenes have been described with differing mechanisms of action but with the common property of inducing morphologic alteration of cells in culture. Subclonal lines of oncogene expressing cells have been shown to produce tumors in vivo. Expression of the N-ras oncogene in embryo fibroblast NIH/3T3 cells has been demonstrated to increase radioresistance in vitro, and these results have been confirmed and extended to human cell lines expressing the c-raf oncogene. In the present report, we have examined the effects of expression of the c-fms, v-abl, or v-myc oncogene in a clonal hematopoietic progenitor cell line 32D cl 3. The 32D cell line is nonmalignant in vivo and is dependent upon a source of Interleukin-3 (IL-3) for growth in vitro. The radiation survival of 32D cl 3 cells transfected and expressed in the c-fms oncogene showed significant increase in the radioresistance at both 5 cGy/min and 116 cGy/min. A clone of 32D cl 3 transfected and expressing the v-myc oncogene demonstrated increased radioresistance at both dose rates. Results of split dose experiments suggested significant repair of sublethal irradiation damage of 32D-v abl cells. Results were compared with expression of the same v-abl oncogene in the NIH/3T3 embryo fibroblast cell line. The data demonstrate that gamma irradiation resistance is significantly increased by each oncogene expressed in 32D cl 3 cells. The data on cell line 32D cl 3 may correlate with the radioresistance of v-abl expressing human hematopoietic cell malignancies treated by irradiation therapy. PMID- 1938519 TI - Acute and late radiation damage in mouse bladder: a comparison of urination frequency and cystometry. AB - Functional damage in the mouse bladder was measured sequentially from 1 to 53 weeks after irradiation with a range of X ray doses (10 to 30 Gy). Damage was assessed from the independent assays of urination frequency and cystometric measurement of bladder volume at a constant intravesical pressure. There was an early, transient wave of damage from 1 to 3 weeks after bladder irradiation. During this period the urination frequency was increased to greater than or equal to 2 times control levels in 20 to 70% of the mice (depending on dose) after 15 to 30 Gy. Bladder volume was reduced to less than or equal to 50% of control values in 20 to 40% of the mice after doses of 20 to 30 Gy. This early damage usually lasted for less than 1 week and occurred at times ranging from 5 to 21 days, independent of dose. There was no significant correlation between response as measured by the two assays on an individual animal basis during the early period. The incidence of reduced bladder volume, measured cystometrically in anesthetized mice, tended to be less than the incidence of increased urination frequency, measured in non-anesthetized animals. Late bladder damage developed from 16 to 40 weeks after doses of greater than or equal to 20 Gy, and the time of onset was inversely related to dose. Less than 20% of mice treated with 10 to 15 Gy developed late bladder damage as assessed by increased urination frequency or reduced bladder volume. Late bladder damage was irreversible and there was a good correlation between response of individual animals as measured by the two assays. We conclude that changes in both urination frequency and bladder volume can be used as quantitative measures of early and late functional damage after bladder irradiation. The early, transient damage was not associated with changes in the urothelium or muscle layers of the bladder, whereas the late, persistent damage was accompanied by epithelial denudation and focal hyperplasia, with fibrosis and ulceration after higher doses. PMID- 1938520 TI - Incorporation of cortical bone autografts following intraoperative extracorporeal irradiation in rabbits. AB - In an experimental study using 60 rabbits, a cortical bone segment of the unilateral tibial diaphysis was resected, irradiated extracorporeally, and reimplanted immediately as an autograft. The subsequent process of graft incorporation was examined over a 26-week period by roentgenography, histology, and histomorphometry. The irradiation doses were 0 (control), 50, 100, and 200 Gy. Roentgenographic and histologic examinations revealed that cortical bone autografts irradiated at 50 to 200 Gy were incorporated in the same manner as non irradiated controls. By histomorphometry, the mean unresorbed fraction of the grafts at 6 weeks post-implantation was estimated to be 88.4% for the control group and 89.4% for the 200 Gy group. That of 26 weeks postimplantation was 17.5% for the control and 28.5%, 26.1%, and 27.8% for the 50, 100, and 200 Gy groups, respectively. Cumulative new bone formation showed a similar but inverse pattern of difference between the control and irradiated groups at 26 weeks. However, these differences were not statistically significant and were considered to be slight when compared with the overall similarity of the process. The total cross sectional area of cortical bone at 26 weeks was similar to that of the contralateral side in all groups. In none of the adopted evaluation methods was any difference detected among the three irradiated groups with different doses. The results of this study suggest that extracorporeal irradiation of autografts at the specified doses impairs possible cellular contribution of the grafted marrow to the incorporation process, but does not interfere with the contribution of the matrices. The results provide useful information concerning the method of limb salvage surgery using intraoperatively-irradiated autografts. PMID- 1938521 TI - In vivo radiosensitizing activity of a new fluorinated hypoxic cell radiosensitizer, KU-2285, in combination with radiation dose fractionation. AB - Since most clinical radiotherapy is given as multiple small irradiation fractions, the present study was undertaken to test the in vivo radiosensitizing activity of a new hypoxic cell radiosensitizer, KU-2285, in combination with radiation dose fractionation. Radiosensitizing activity was measured by a growth delay assay using a transplanted mammary tumor in C3H/He mice, and by an in vivo in vitro assay using the SCC VII tumor. KU-2285 was injected intraperitoneally 30 min before irradiation in all experiments. The in vivo-in vitro assay using SCC VII tumors showed that 12.5 micrograms/g of KU-2285 sensitized the tumors to irradiation (5 Gy/fr x 5 fr/48 hr or 6 Gy/fr x 3 fr/48 hr). KU-2285 also sensitized the transplanted mammary tumors to fractionated irradiation. We concluded that KU-2285 was able to sensitize two different murine tumors when given in combination with radiation dose fractionation. PMID- 1938522 TI - Rapid liver metabolism, urinary and biliary excretion, and enterohepatic circulation of 16 alpha-radioiodo-17 beta-estradiol. AB - The radiohalogenated estrogen 16 alpha-[123I]iodo-17 beta-estradiol ([123I]E2) is emerging as a diagnostic tool for imaging of ER-rich malignant tumors, with potential application for site-directed radiotherapy. Clinical use requires an accurate accounting for the biodistribution of the radioactivity, including an assessment of its enterohepatic circulation. We investigated the metabolism and circulation of [125I]E2 in the enterohepatic system in swine, a pharmacokinetic model that resembles humans. With indicator dilution methods, we found that, after its injection into the portal vein, more than 99% of [125I]E2 was cleared from the blood by the liver during the first pass. Water-soluble metabolites were then partly released into the blood and partly excreted into bile. After injection of [125I]E2 into the external jugular vein, one-third of the radioactivity was excreted in bile and two-thirds in the urine. More than 90% of the radioactivity in urine and bile was that of [125I]E2-glucuronide or [125I]E2 sulfate; only a very small fraction of the excreted radioactivity was from free 125I. Radioactivity in bile collected from one swine after i.v. injection of [125I]E2, and then infused into the proximal duodenum of a second swine, was almost totally absorbed during passage through the intestine at 5-7 hr after infusion. The reabsorbed radioactivity was cleared in the urine. PMID- 1938524 TI - On the impact of tissue inhomogeneity corrections in clinical thoracic radiation therapy. AB - The magnitude and impact of the corrections required for calculated absorbed doses due to the presence of real anatomic inhomogeneities were studied in 100 "standard" clinical thoracic cases. Correction factor distributions were generated with the equivalent tissue-air ratio method. The correction factors at the point of target absorbed dose, the average within the high dose area, and the average and maximum within the irradiated lung tissue were determined. Results indicate that among patients undergoing similar treatment techniques and radiation energy, correction factors can vary greatly. The diversity in anatomy, geometry, and density emphasizes the need for patient-specific dose calculations if the appropriate accuracy is to be achieved. Even for simple parallel-opposed fields encompassing the mediastinal and bilateral lung regions, the correction at the point of target absorbed dose was found to be as much as 5 to 16% for photon energies between 60Co and 25 MV. The average correction factor within the high dose region was generally comparable in value. For beams that traverse the lungs obliquely, the correction factor at the point of target absorbed dose was as large as 1.21 with 25 MV photons. These values correlated linearly with the lung pathlength preceding the point. Within lung tissues, the corrections were often more dramatic. Using the dose response curve for normal lung tolerance, the clinical consequence of ignoring the increased dose to lung tissue can be predicted. For 100 patients, the use of uncorrected dose would result in an underestimation of the risk for radiological radiation pneumonitis by 7% on average and by as much as 19% maximally. These data suggest that whenever lung tissue and/or tumor response levels are critical, as is often the case for radical therapy, multi-center trials, and dose response determination, inhomogeneity corrections should be implemented. PMID- 1938523 TI - Dynamic field shaping to optimize stereotactic radiosurgery. AB - A dynamic field shaping collimation system is evaluated for use in stereotactic radiosurgery of non-spherical lesions. The concept is as follows: (a) use the existing circular collimators to define a cone which encompasses the maximum dimensions of the target volume; (b) position two sets of independent rectangular photon collimators immediately upstream from the circular aperture and allow each collimator to have independent translational and rotational motion in order to define, for each increment of arc, a polygonal field shape having up to four straight and four curved edges which enscribe the beam's eye projection of the target; (c) modify the translational and rotational position of each independent collimator with each change in arc angle to continuously shape the instantaneous field to the target shape. A prototype device has been constructed and uses vane control technology developed in a related research project in electron arc therapy. The efficacy of this device is illustrated by dose calculations and measurement based on actual clinical data. Dose volume histograms are used to compare the dose received by three techniques: single isocenter treatment using a single circular aperture, dual isocenter treatment, and single isocenter treatment using dynamically shaped fields. Doses were calculated throughout the brain using a volume grid of 3 mm spacing. Dose volume histograms comparing dose within the target volume and brain volume excluding target volume, as well as computed isodose distributions, demonstrate the possible reduction in normal tissue dose burden while simultaneously preserving dose uniformity throughout the prescribed target volume. This simple four-vane collimation system may provide a viable alternate treatment technique for non-spherical lesions. PMID- 1938525 TI - Radiation therapy for unresectable rectal cancer. AB - The standard approach to patients with unresectable rectal cancer is pre-op radiation therapy followed by surgery. To determine the impact of RT on local failure and survival, we present an analysis of our preliminary results of this approach in patients with unresectable rectal cancer. A total of 22 patients were analyzed (9 primary, 13 recurrent). The median follow-up was 22 months. There were two groups of patients. Group 1 included 12 patients with unresectable tumors in whom surgery was planned following pre-operative radiation therapy. Group 2 included 10 patients in whom no surgery was planned following radiation therapy due to extensive pelvic bone destruction. The whole pelvis received 4680 cGy followed by a boost of 360-1440 cGy. Six underwent brachytherapy. For the total patient group, the 3-year actuarial survival was 52% (Group 1: 91% vs Group 2: 30%). Patterns of failure as a component of failure were: local failure (or local progression): 50%, abdominal: 23%, and distant: 9%. The dose of pelvic radiation had no significant impact on the local failure rate (5040 cGy: 55% vs greater than 5700 cGy:45%). None of the seven patients with negative margins developed local failure compared with 73% of those with positive margins. The complete resection rate in Group 1 patients was 58%, and all are alive without local failure. Further follow-up will be needed to determine the ultimate local failure and survival rates. PMID- 1938526 TI - Combined radiation therapy, mitomycin C, and 5-fluorouracil for locally recurrent rectal carcinoma: results of a pilot study. AB - Twenty-two patients underwent combined radiation therapy (XRT), mitomycin C (MMC), and 5-fluorouracil (5FU) for rectal carcinoma, locally recurrent following either abdominoperineal or anterior resections. All patients presented with symptomatic unresectable pelvic cancer. The protocol XRT doses were 45-50 Gy/20/4 6 weeks. Chemotherapy consisted of MMC 10 mg/m2 on day 1, and 5FU 15 mg/kg/day on days 1, 2, and 3 of XRT, both given by intravenous bolus injection. Only 2 of 22 patients remained NED at 5 years following treatment. All but four patients eventually experienced progression of pelvic disease. Ten of 22 patients were unable to complete the treatment protocol because of excessive acute hematological and gastrointestinal toxicity. Five patients developed neutropenic sepsis, one of whom died. Combined XRT, MMC, and 5FU as used in this study had no apparent advantage over XRT alone in terms of pelvic disease or survival, and produced significant toxicity. PMID- 1938527 TI - Incompletely resected rectum, recto-sigmoid, or sigmoid carcinoma: results of postoperative radiotherapy and prognostic factors. AB - Postoperative radiotherapy was given in 40 patients with gross or microscopic pathologically proven residual disease after surgical resection of rectum, recto sigmoid, or sigmoid carcinoma. The radiotherapy target volume included the pelvis with (9 patients) or without (31 patients) the perineum. Median total dose of radiation was 50 Gy (range 30-60). One patient received 30 Gy, 10 received greater than 30 to 40 Gy, 13 received greater than 40 to 50 Gy, and 16 patients received greater than 50 to 60 Gy. The median follow-up in the survivors (16 patients) was 53 months (range: 16-85). Probability of survival with censoring for death due to intercurrent disease was 36% at 5 years. Survival for patients with microscopic residual disease (21 patients) was 40% at 5 years compared to 12% for those with gross residual disease (19 patients) (p = 0.09). Twenty-five patients relapsed. All but one relapse occurred earlier than 50 months after radiotherapy. Approximately half (12/25) of the relapses were observed within 6 months after radiotherapy. Local relapse inside the radiotherapy portals was observed in 9/40 (22%) patients. Therapy-related urogenital complications occurred in no patient and gastro-intestinal complications in three patients (7%). In one patient they were scored WHO grade 4 and in two patients WHO grade 3. Prognostic factors were analyzed using the Cox proportional hazards model. For survival differentiation, grade (p less than 0.001), stage (p = 0.04), and perineal irradiation (p = 0.03) were independent prognostic factors. With relapse free survival as the endpoint, only stage (p = 0.003) was a statistically significant prognostic factor. There was a trend toward a better relapse-free survival when the perineum was included in the radiation portals (p = 0.09). PMID- 1938528 TI - Significance of prone positioning in planning treatment for esophageal cancer. AB - The treatment of esophageal cancer is made difficult by the close proximity of the esophagus to the spinal cord and the requirement to treat the esophageal target volume to doses greater than or equal to 60 Gy while limiting the spinal cord dose to less than or equal to 46 Gy. By placing the patient in the prone position, the esophagus can be displaced away from the spinal cord. We explored the results of this commonly used technique on 16 patients who have undergone simulation in both supine and prone positions. Both AP and lateral orthogonal radiographs were obtained in both positions. The distance between contrast material in the esophagus and spinal cord was noted in at least four transverse planes through the thoracic esophagus on each of the 16 patients. These four transverse planes were located at 3 cm above the carina, at the carina, 3 cm below the carina and 6 cm below the carina. The mean displacement (+/- 1 SD) of the esophagus away from the spinal cord when the patient was in the prone position compared to supine at each of these levels was 1.3 (+/- 0.8) cm, 1.8 (+/ 0.9) cm, 1.8 (+/- 1.0) cm, and 1.9 (+/- 1.1) cm. The range of displacement for all 64 displacement determinations was 0 to 4.2 cm with a mean of 1.7 cm. To evaluate further the consequences of prone positioning on treatment planning and doses received to target volumes and critical structures, we performed 3 dimensional treatment planning with a patient in both prone and supine positions. The requirements were to achieve a tumor volume dose of 60 Gy while keeping the spinal cord dose below 46 Gy. Two types of conventional treatment plans were examined in prone and supine positions. A 6-field plan consisted of delivery of 40 Gy through a large 3-field beam arrangement followed by delivery of 20 Gy through a similar 3-field cone down. An 8-field plan involved the delivery of 30 Gy through AP/PA beams followed by a 3-field beam arrangement to 40 Gy and a subsequent 3-field cone-down for the final 20 Gy. Comparison of dose volume histograms revealed that the 6-field plan spared relatively more heart whereas the 8-field plan spared relatively more lung. Regarding the primary consideration of coverage of target volume with avoidance of spinal cord, prone positioning was superior to supine positioning whether 6- or 8-field arrangements were used. PMID- 1938529 TI - Pharmacologic erection with intracavernosal injection for men with sexual dysfunction following irradiation: a preliminary report. AB - Impotence is a possible consequence of treatment of pituitary adenomas and prostatic carcinomas. Following pituitary irradiation, the effect has been attributed to decreased gonadotrophins, while a variety of mechanisms, primarily vascular and neurogenic, have been proposed to explain the impotence following irradiation of prostatic carcinomas. Men with impotence of any etiology have been entered on a program to evaluate prospectively the efficacy of intracavernosal injection of vasoactive compounds in producing a satisfactory erection with pharmacologic means. Ten of these men had developed impotence following therapy for pituitary adenomas (2) or prostatic carcinomas (8). Test doses of 0.1 to 0.5 ml of a phentolamine (1 mg/ml) and papaverine (30 mg/ml) mixture were used; the dose was titrated to produce an erection deemed sufficient for vaginal penetration. All patients achieved a satisfactory response (i.e., tumescence and rigidity) lasting 10 minutes to 3 hours. Seven patients have continued in the pharmacologic erection program, with six patients functioning normally, and the remaining patient noting decreased tumescence after 18 months of treatment, but adequate erections are maintained with supplemental penile ring. Two patients have discontinued intracavernosal injections due to inconvenience, and one patient was lost to follow-up. Recent substitution of prostaglandin E1 (PGE1) has produced similar results and has replaced the phentolamine-papaverine combination. These preliminary results indicate that pharmacologic erection can be achieved in patients with impotence related to the treatment of pituitary and prostatic neoplasms and represents a reasonable alternative to implanted penile prostheses. PMID- 1938530 TI - The effect of laryngeal irradiation on pharyngoesophageal motility. AB - The upper esophageal sphincter (UES) receives the full radiation dose during external beam radiotherapy to the adjacent larynx. The aim of the study was to assess the effects, if any, of radical laryngeal radiotherapy on motility patterns in the pharyngoesophageal segment. A strain gauge assembly and a digital manometric recorder were used to assess 19 patients 13 to 71 months after irradiation of T1 to T3 glottic cancer to a central dose of 52.5 to 55.7 Gy in 20 daily fractions. Results were compared with those of 23 healthy controls. Tonic lower esophageal sphincter (LES) pressure, distal peristaltic contraction, tonic UES pressure, and eight parameters of pharyngoesophageal dynamics during water and bread swallows were studied. No difference was found between the two groups in tonic LES pressure, peristaltic amplitude, or tonic UES pressure. Water swallow pharyngoesophageal wave velocity was significantly lower in patients than in controls, and the irradiated group also showed a trend toward increased duration of the distal esophageal peristaltic wave. The reduction in upper esophageal wave velocity was associated with the interval following irradiation. The post-treatment interval was also inversely related to the amplitude of UES after-contraction, and associated with an increase in wave duration throughout the pharyngoesophageal segment. A study of 23 laryngectomy specimens, 5 of which had been removed following radiotherapy, failed to identify pathological features in nerves or muscle which characterised previous laryngopharyngeal irradiation. We conclude that laryngeal irradiation has no effect on upper or lower esophageal sphincter tone but causes an increase in wave duration and a reduction in wave velocity in the pharyngoesophageal segment. These changes are independent of age and sex and are not associated with pathological features like the neural degeneration described in the myenteric plexus of irradiated rectum. PMID- 1938531 TI - Improved linac dose distributions for radiosurgery with elliptically shaped fields. AB - Stereotactic radiosurgery techniques for a linear accelerator typically use circular radiation fields to produce an essentially spherical radiation distribution with a steep dose gradient. Target volumes are frequently irregular in shape, and circular distributions may irradiate normal tissues to high dose as well as the target volume. Improvements to the dose distribution have been made using multiple target points and optimizing the dose per arc to the target. A retrospective review of 20 radiosurgery patients has suggested that the use of elliptically shaped fields may further improve the match of the radiation distribution to the intended target volume. This hypothesis has been verified with film measurements of the radiation distribution obtained using elliptical radiation beam in a head phantom. Reductions of 40% of the high dose volume have been obtained with elliptical fields compared to circular fields without compromising the dose to the target volume. PMID- 1938532 TI - Study of treatment variation in the radiotherapy of head and neck tumors using a fiber-optic on-line radiotherapy imaging system. AB - On-line radiotherapy imaging systems allow convenient daily acquisition of portal images for treatment verification. The information can also be used to study treatment variability. Using a prototype fiber-optic imaging system, we have measured the treatment variation of 17 head and neck patients. Daily digital portal images were acquired for the on-cord left and right lateral fields. Treatment variations were quantified using the Cumulative Verification Image Analysis (CVIA) method developed at our institute. In the CVIA method, daily portal images were aligned according to three anatomical points predefined on a digitized simulation, or prescription, image. After each image alignment, the block position was cumulated in a bit-map and superimposed on the prescription image to give a cumulative verification summary image. Iso-frequency distributions, or contours, of the block overlap were calculated and examined with respect to the prescription treatment area. The range of the treatment variation was large for the 17 patients. On average, separation of the 0% to 100% block overlap contours was about 10 mm, and the 20% to 80%, 5 mm. The block overlap contours were also used to calculate the frequency with which the prescription area as defined on the simulation film had been treated. The fraction of the prescription area treated depended on the accuracy of the treatment setup and patient repositioning, as expected. At best, approximately 95% of the prescribed area was irradiated 100% of the time during the entire course of radiotherapy. At worst, approximately 70% of the prescribed area was irradiated 100% of the time. These results demonstrate that despite immobilization, large setup variation can still occur. Presenting treatment variation data as population averages does not reflect on the large variation that may be observed in the individual patient. PMID- 1938533 TI - A simple technique for irradiation of recto-anal cancers with electrons using an internal anal shield. AB - A method of treating the primary site of recto-anal cancers using an en face electron beam in combination with an internal lead shield in the anus has been developed. Dose measurements using lithium fluoride thermoluminescent dosimetry indicate that the internal anal shield reduces the dose to the uninvolved anal wall by up to a factor of two while leaving the dose to the primary tumor site unaffected. Because the internal anal shield is placed in the anus during treatment, this system leads to a more precise daily positioning of the shield compared to the setup using an external shield alone. This technique has been used to treat two patients with anal cancer who tolerated the treatment well with no acute side effects. Both patients are now disease free, more than 30 months after their radiation treatment, without any treatment-related sequelae. PMID- 1938534 TI - Dosimetry of the breast for determining carcinogenic risk in mantle irradiation. AB - Development of secondary malignancies following treatment of Hodgkin's disease with radiation (central axis midline dose of 3600-4500 cGy) is a recognized risk, and the incidence in breast cancer has been reported to increase by a factor of 4.3 (95% confidence level 2.0 to 8.4) for patients treated with mantle irradiation. Increased incidence of breast cancer has also been shown in atomic bomb survivors, women who underwent multiple fluoroscopic examinations, and women treated for postpartum mastitis. The dose response, however, for radiation dose above 1000 cGy is virtually unknown. Quantitative analysis of carcinogenesis after radiation is exacerbated by the large dose gradient across the breast (300 4200 cGy for midline doses of 4000 cGy), large individual variation in breast size and treatment field position. We have developed differential dose volume histograms calculated using a 3-dimensional (Eg TAR) algorithm as a potential tool for retrospective and prospective epidemiological evaluation. The breast volume forms a bimodal distribution with respect to dose and with further analysis other quantities, such as mean dose and integral dose, can be calculated from the histograms. Using the mean dose, the linear model for carcinogenesis predicts an increased incidence of secondary breast cancer by a factor of 11.6 and 9.6 for the left and right breast, respectively. The dose calculations has been corrected for inhomonogenities 3-dimensionally and test of the accuracy has been included. PMID- 1938535 TI - Evaluation of an ingestible telemetric temperature sensor for deep hyperthermia applications. AB - We have investigated the potential of an ingestible thermometric system (ITS) for use with a deep heating system. The ingestible sensor contains a temperature sensitive quartz crystal oscillator. The telemetered signal is inductively coupled by a radiofrequency coil system to an external receiver. The sensors, covered with a protective silicon coating, are 10 mm in diameter and 20 mm long and are energized by an internal silver-oxide battery. Experimental studies were carried out to investigate the accuracy of the system and the extent of reliable operation of these sensors in an electromagnetic environment. Different measurements were repeated for five sensors. Calibration accuracy was verified by comparison with a Bowman probe in the temperature range 30 degrees C to 55 degrees C. Linear regression analysis of individual pill readings indicated a correlation within +/- 0.4 degrees C at 95% prediction intervals in the clinical temperature range of 35 degrees C to 50 degrees C. Further work is required to improve this accuracy to meet the quality assurance guidelines of +/- 0.2 degrees C suggested by the Hyperthermia Physics Center. Response times were determined by the exponential fit of heat-up and cool-down curves for each pill. All curves had correlation coefficients greater than 0.98. Time (mean +/- SE) to achieve 90% response during heat-up was 115 +/- sec. Time to cool-down to 10% of initial temperature was 114 +/- 4 sec. The effect of the external antenna and sensor spacing and the angle of orientation of the sensor relative to the antenna plane were also studied. Electromagnetic interference effects were studied by placing the sensor with a Bowman probe in a cylindrical saline phantom for the tests in an annular phase array applicator. Different power levels at three frequencies- 80, 100, and 120 MHz--were used. Accurate temperature readings could not be obtained when the electromagnetic power was on because of interference effects with the receiver. However, the temperatures read with the ITS immediately after the electromagnetic power was switched off correlated well with the Bowman probe readings across the power categories and the three frequencies used. The phantom was heated to steady state, with a Bowman probe placed at the central axis of the cylinder used as control. During the heat-up period and the steady state, the mean difference (+/- SE) between the ITS and Bowman probe was 0.12 degrees C (+/- 0.05 degrees C).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1938536 TI - A prospective study of ultrasound localization for renal shielding. AB - Accurate and reproducible shielding of sensitive tissues is essential in clinical radiotherapy. Renal localization is necessary when the kidneys are to be shielded during upper or whole abdominal radiotherapy. Despite extensive clinical experience with intravenous contrast media for renal localization, ultrasound has been proposed as a safer, more cost-effective alternative. In a prospective study, we assessed the accuracy of renal localization by ultrasound. Results show that ultrasound localization covers only 56.5 +/- 27.0% of the renal outline on average; moreover, the ultrasound designed shield results in 57.2 +/- 20.4% of its area being superfluous. Possible explanations and modifications are discussed. We urge others using ultrasound localization for renal shielding to assess its accuracy before using these shields in clinical practice. PMID- 1938537 TI - Gastrointestinal malignancies: radiologic staging and follow-up. PMID- 1938538 TI - Predicting normal tissue injury in radiation therapy. AB - We tested three radiobiologic models, the nominal standard dose (NSD), the biologic index of reaction (BIR), and the linear quadratic (LQ) models to determine which best predicts normal tissue injury in radiation therapy. Clinical data for radiation myelopathy, rib fracture and pericardial effusion were used for all three models to predict injury. We assumed that on the average injuries occurred at higher equivalent doses of radiation than were received by patients who were not injured. We used a t-test to determine whether there were in fact significant differences in the mean values of the equivalent doses among the injured and non-injured. The means were calculated for the four sets of injury by the three models. For the LQ model it was necessary to choose a value for the parameter alpha/beta; the results were not sensitive to the choice over the range of 1/2 to 12 Gy. None of these models showed a significant difference between injured and non-injured patients for all four sets of data. The BIR model showed significant differences in three sets, the LQ model was significant in two and marginally significant in one set, and the NSD was significant in two sets. This analysis illustrates therefore, that the linear quadratic model can be adopted for analysis of clinical data with results that are no worse and possibly better than the NSD model. PMID- 1938539 TI - Accelerated repopulation: friend or foe? Exploiting changes in tumor growth characteristics to improve the "efficiency" of radiotherapy. AB - Accelerated repopulation (rapid multiplication of surviving clonogens) during a course of radiation therapy may contribute to local failure. This possibility has prompted accelerated treatment programs in an attempt to reduce overall treatment time, thereby minimizing the impact of repopulation. However, accelerated dose delivery at the start of treatment may not be advantageous since many of the tumor cells are likely to be hypoxic (non-cycling cells) and therefore relatively radioresistant. Conversely, accelerated treatment is likely to be most helpful later in treatment when the tumor has shrunk and accelerated repopulation of clonogens is a dominant factor. A series of calculations are presented that stimulate changes in tumor size, clonogen number, clonogen repopulation, and growth fraction during a course of fractionated radiation treatments for an idealized 2 cm diameter spherical tumor. The efficiency of each fraction of radiation is calculated for different radiation fractionation schemes. Efficiency is defined as the change in Log clonogen number (reflecting cell death due to radiation minus repopulation that has occurred during the interval between fractions) per Gy. These calculations suggest that relatively low total daily doses (approximately 2 Gy) are most efficient early in treatment. Higher daily doses are less efficient since the growth fraction is relatively low at the start of treatment. Later in treatment, as the tumor shrinks and the growth fraction approaches 1, accelerated repopulation becomes a major problem and higher total daily doses are more efficient. At this point, accelerated hyperfractionation should be used to increase the daily dose without exposing normal tissues to high fraction sizes. Thus, changes in tumor growth characteristics are exploited and dose delivery can be optimized by escalating daily irradiation doses during a course of fractionated irradiation. Strict interpretation of these conclusions must be tempered by the various assumptions and uncertainties included in this model. The concept of efficiency is useful since it reflects the competing effects of clonogen repopulation and radiation induced clonogen sterilization. PMID- 1938540 TI - Anal cancer: radiation and concomitant continuous infusion chemotherapy. PMID- 1938541 TI - Intraoperative radiotherapy for pancreatic cancer--requiem or revival? PMID- 1938542 TI - Papillary cystic neoplasm of the pancreas. PMID- 1938543 TI - A bottom limit to the utility of mammography? PMID- 1938544 TI - Irradiation of epithelial skin cancer. PMID- 1938545 TI - Hodgkin's disease in the deep lymph nodes of the arm 18 years following irradiation of Hodgkin's disease in the ipsilateral axilla. PMID- 1938546 TI - Proposed universal standard for specifying schedules. PMID- 1938547 TI - Dedication to Frank Ellis. PMID- 1938548 TI - The dose-rate effect revisited: radiobiological considerations of importance in radiotherapy. AB - A wide range of dose-rates have been used in radiation biology and radiation therapy, extending from a few cGy per day to hundreds of Gy in a fraction of a second. The dose-rate range of importance in radiotherapy extends from about 0.1 Gy/hr to several Gy/min. In this range, the fraction of cells killed by a given dose decreases as the dose-rate is reduced, principally because of the repair of sub-lethal damage. In some cell lines, an inverse dose-rate effect is observed where, over a narrow range of dose-rates, the effectiveness of a given dose increases with decreasing dose-rate if cells move through the cycle and are arrested in G2, which is a radiosensitive phase. In recent years data have accumulated for cells of human origin. About 40 data sets have been analyzed for values of the survival curve parameters and the rate of repair of sub-lethal damage. These data have been used to address three questions of relevance to radiotherapy. (1) The proposal to use pulsed rather than continuous irradiation in interstitial brachytherapy. (2) The equivalence of high dose-rate and low dose rate intracavitary treatments for carcinoma of the cervix. (3) An analysis of equivalent doses for a range of dose-rates in interstitial implants. PMID- 1938549 TI - Fractionated high dose-rate versus low dose-rate regimens for intracavitary brachytherapy of the cervix: equivalent regimens for combined brachytherapy and external irradiation. AB - The conventional treatment for carcinoma of the uterine cervix is a combination of external teletherapy and low dose-rate (LDR) intracavitary brachytherapy. Recently, however, there has been an increasing trend toward the use of high dose rate (HDR) brachytherapy, in combination with external irradiation. The question is addressed of designing HDR treatments that will produce equivalent results to the more conventional protocols. We argue that for the unique case of radiotherapeutic treatment of carcinoma of the cervix, the criterion for producing an equivalent treatment should be based on the matching of early, not late, effects. In essence, this is because the dose to the tissues at risk for late effects is usually significantly smaller than the prescribed dose. When this effect is factored in with the different shape of dose-response curves for early and late effects, we conclude that, in the majority of cases, late effects will be no worse in a HDR regimen than a LDR regimen, provided that the corresponding doses have been matched to produce equal early effects. We provide a formalism whereby equivalent protocols can be designed for combined "external + HDR brachytherapy" regimens to match current "external + LDR brachytherapy" schedules. Using extensive basic radiobiological in vitro data derived from various cells of human origin, we provide specific examples of equivalent "external + HDR brachytherapy" regimens for 23 current "external + LDR brachytherapy" commonly-used schedules. PMID- 1938550 TI - Comparison of high and low dose rate remote afterloading for cervix cancer and the importance of fractionation. AB - Analysis of the data obtained from a survey of 56 institutions treating a total of over 17,000 cervix cancer patients with high dose rate (HDR) remote afterloading, shows that the average fractionation regimen is about 5 fractions of 7.5 Gy each to Point A, regardless of stage of disease. Comparison with historical controls treated by the same clinicians at low dose rate (LDR), showed that 5-year survival was statistically significantly better for HDR versus LDR for Stage III patients (47.2% compared to 42.6%, P = 0.005) and for all patients pooled together (60.8% vs. 59.0% P = 0.045). Morbidity rates were considerably lower for HDR versus LDR for both severe (2.23% vs. 5.34%, P less than 0.001) and moderate plus severe complications (9.05% vs. 20.66%, P less than 0.001). There is an apparent geometrical advantage of HDR intracavitary therapy in that there is a reduction in the "hot-spot" rectal and bladder doses relative to Point A of, on average, (13 +/- 4)% for the HDR compared to the LDR treatments. Fractionation of the HDR treatments significantly influenced toxicity: morbidity rates were highly significantly lower for Point A doses/fraction less than or equal to 7 Gy compared with greater than 7 Gy for both severe injuries (1.28% vs. 3.44%, P less than 0.001) and moderate plus severe (7.58% vs. 10.51%, P less than 0.001). The effect of dose/fraction on cure rates was equivocal. Finally, the data showed that for conversion from LDR to HDR the total dose to Point A was reduced on average by a factor 0.54 +/- 0.06. PMID- 1938551 TI - Hydralazine does not increase hypoxia in tumors growing in preirradiated tissue. AB - There is a growing interest in the exploitation of hypoxia in solid tumors for therapeutic gain by the use of hypoxic cytotoxins and other agents. Tumor hypoxia can be greatly increased in a number of animal tumor models with the vasoactive drug hydralazine (HDZ), and in some cases this potentiates the effect of drugs that are selectively toxic to hypoxic cells. Our interest was to determine if HDZ would also increase tumor hypoxia in tumors growing in previously irradiated normal tissue- a situation such as might be found in the clinic with regrowing solid tumors after radiotherapy. SCCVII tumors in untreated mice were compared with tumors growing in a previously irradiated tissue with respect to their level of hypoxia in response to HDZ. HDZ increased tumor hypoxia in the tumors from unirradiated mice as measured by 14C-misonidazole binding. However, HDZ had little or no effect on tumor hypoxia in tumors growing in previously irradiated sites. We also showed that the pre-HDZ extent of hypoxia was higher in tumors growing in a previously irradiated tissue. This may in part explain the lack of effect of HDZ in these tumors. The lack of response of the tumors growing in irradiated sites suggests a limitation on the use of HDZ in combination with specific hypoxic cytotoxins or other chemotherapeutic drugs in the treatment of recurrent solid tumors. The data also show that if such tumors have an elevated hypoxic fraction relative to their counterparts growing in untreated sites, these tumors might be intrinsically more resistant to conventional radiotherapy, but, on the other hand, might be sensitive to bioreductive drugs and more likely to be radiosensitized by a hypoxic cell sensitizer. PMID- 1938552 TI - Studies of dose-fractionation on early and late responses in pig skin: a reappraisal of the importance of the overall treatment time and its effects on radiosensitization and incomplete repair. AB - Studies in pig skin have examined the effects of dose fractionation on the acute radiation response. The variation in ED50 values for moist desquamation for doses given as 1-48 fractions over less than or equal to 16 days were best fitted by a log-log plot of iso-effect dose against the number of fractions; the slope of this plot indicated a fraction number exponent (N) of 0.42 +/- 0.007. Based on the assumptions made in applying the linear-quadratic (LQ) model, the alpha/beta ratio was found to decrease with decreasing per fraction: for doses given as 6-27 Gy per fractions the alpha/beta ratio was 8.74 +/- 0.48 Gy, whereas for doses of 2.55-6 Gy per fraction it was only 0.85 +/- 0.29 Gy. A simple approach to a time factor could not be used to calculate iso-effect doses for acute reactions in pig skin when treatment time was increased from less than or equal to 16 days to 28 39 days. This was due to the opposing effects of radiosensitization and repopulation when the cell cycle time of epidermal basal cells was shortened. For late dermal necrosis in pig skin, repair of sublethal damage was not completed in 24 hr. This finding has a significant effect on the interpretation of the results of fractionation studies using this late endpoint. Expressed in terms of a simple power-law function, there was a significant change in the fraction number exponent "N" from 0.43 +/- 0.007 to 0.37 +/- 0.006 for the complete and incomplete repair data, respectively. Many of the fractionation effects reported for acute and late damage to pig skin would appear to be in excellent agreement with those for human skin. PMID- 1938553 TI - Apparent rates of proliferation of acutely responding normal tissues during radiotherapy of head and neck cancer. AB - Total doses, fraction sizes, and overall times reported to give "tolerance level" reactions in oral, pharyngeal, or laryngeal mucosa vary greatly in different countries. The variation in fraction size reviewed here is from 1.15 Gy (France) to 3.4 Gy (UK), and in overall time from 11 days (UK) through 3, 4, and 5 weeks (UK and Canada) to 7 weeks (USA and France). Using linear quadratic corrections for fraction size, and regression of the resulting "LQ doses" against overall time, it is found that the average rate of increase of dose for these normal tissue reactions is gamma/alpha = 63 to 69 cGy per day (along the initial slope of the underlying dose-response curve), which corresponds to 53 to 65 cGy per day when 2 Gy fractions are used. The range of uncertainty overlaps with that of estimated tumor proliferation rates in the head and neck by other authors, but there is no trend for these normal tissues to be proliferating consistently faster than tumors in the same sites. These conclusions must be interpreted with caution because of differences in acceptance of reaction level, treatment volume, and dose specification. PMID- 1938554 TI - Sublethal damage, potentially lethal damage, and chromosomal aberrations in mammalian cells exposed to ionizing radiations. AB - Sublethal and potentially lethal damage are abstract terms that originated and were defined without reference to molecular and subcellular entities in which such radiation damage was registered. The establishment of a cause-and-effect relationship between chromosome fragment loss and cell killing by ionizing radiations, along with a substantial body of knowledge in radiation cytogenetics, allows a definition of these terms in a context where hypotheses become testable and progress toward a better understanding of these phenomena is more likely. Accordingly, the simplest hypothesis which best fits the observations is as follows. Most aberrations are exchange types requiring an interaction to form the exchange between two broken regions of a chromosome or chromosomes, that is, a break-pair. Very few single breaks fail to rejoin or restitute, so the vast majority are sublethal. Any such sublethal break may become a potentially lethal break-pair if another sublethal break occurs within some range where it is possible for the two to interact. The proportion of break-pairs in which a mis repair event results in a lethal acentric fragment-producing exchange, can be altered depending on treatment conditions. Such conditions change the balance between "PLD repair" and "PLD fixation." Studies on the control of radiosensitivity have focused on differences in repair processes, but large differences in radiation response may just as well occur with identical repair processes in operation but with different conditions of fixation. PMID- 1938555 TI - The importance of optimal treatment planning in radiation therapy. AB - There are two classes of failure in radiation therapy: local control not achieved and radiation-induced morbidity. Technical developments which permit the employment of treatment volumes which achieve a closer approximation to the target volume can confidently be asserted to yield clinical gains in terms of higher tumor control rates and/or reduced severity/frequency of radiation induced morbidity. The magnitude of the gains and the cost and effort to realize those gains may need to be assessed by the technique of the "clinical trial." Such gains will be the consequence of a higher dose to the target and/or the irradiation of smaller volumes of non-target tissues. An important fact is that unirradiated tissues do not develop radiation-related injury. Selected categories of radiation injuries that appear in non-target tissues are here reviewed. Valuable advances in the technology of radiation therapy are virtually certain for the near term. This bodes well, indeed, for our future patients. PMID- 1938556 TI - Interstitial brachytherapy: past-present-future. AB - This article summarizes and reviews the development of brachytherapy from 1930 to 1990. Its purpose is to highlight the immense contribution made to its underlying science and clinical practice by Dr. Frank Ellis, who has been personally involved with it, in theory and in practice, for that whole half-century. A remarkable achievement in itself, but so much the more when it is seen beside his contributions to other aspects of radiation in the service of man. The early use of solid sources leads on to a discussion of manual afterloading and iridium. This leads on to a quick survey of the development of dosimetry. Thereafter clinical indications are briefly discussed and some published results tabulated. Lastly, some pointers to possible future development and benefits are discussed. Mention is also made of some continuing unresolved problems where new work could help to establish the most appropriate use of brachytherapy. PMID- 1938557 TI - Brachytherapy and function-saving resection of soft tissue sarcoma arising in the limb. AB - The treatment of soft tissue sarcoma of the limb by function-saving resection and brachytherapy (BRT) was systematically studied from 1975 to 1990 at the Memorial Sloan-Kettering Cancer Center, using iridium-192 temporary tumor-bed implants. Initial experiences showed an 88% local control rate in 33 patients who had locally advanced sarcomas, many of which would have required treatment by amputation. The technique also controlled 70% of tumors that abutted or invaded a major neurovascular bundle that was dissected out and preserved. A prospective randomized study (BRT vs no BRT) confirmed the highly significant efficacy of BRT in preventing local recurrence. This salutary effect is mainly seen in high-grade tumors. Major complications of wound healing occurred in the earlier years of this experience. Adoption of improved techniques of surgical wound repair, standardization of radiation dose planning, and in particular, postponing the loading of radiation sources until after the fifth postoperative day has reduced the rate of serious wound complications, to a level not significantly different from that seen after surgical resection alone. These results rival those currently achieved in centers experienced in external beam therapy of soft tissue sarcomas, and offer the advantage of completion of treatment in one relatively short hospital stay. PMID- 1938558 TI - Acute and long-term effects on limb function of combined modality limb sparing therapy for extremity soft tissue sarcoma. AB - A retrospective review is presented on 145 patients who underwent limb-sparing surgery and radiation therapy (with or without adjuvant chemotherapy) for their primary soft tissue sarcomas of the extremities on protocol between 1975 and 1986. The focus on our analysis was the acute and long term toxicity of treatment on limb function. The most common acute complication was skin reaction, occurring in 52 patients (36%). Long term (occurring after more than 1 year following all treatment) treatment complications in the extremity were as follows: bone fracture = 6%; contracture = 20%; pain requiring narcotics = 7%; edema greater than 2+ = 19%; moderate to severe decrease in range of motion = 32%; moderate to severe decrease in manual muscle strength = 20%; orthotic device required = 9%; cane or crutch required = 7%; chronic infection = 9%; and tissue induration = 57%. Three amputations for treatment complications were required. Inclusion of more than 50% of the joint in the radiation portal was associated with a higher frequency of contracture. High nominal standard dose (greater than 1760 rets, greater than 63 Gy at 1.8 Gy per fraction) resulted in more painful limbs as well as limbs with increased edema, decreased manual muscle strength, decreased range of motion, and skin telangiectasias. Edema was more often noted in patients with a longer radiation portal (greater than 35 cm), as was tissue induration. Chronic ulcer or infection was more frequently seen in patients with lower extremity tumors and when more than 75% of the extremity diameter was irradiated. Although chemotherapy given concurrent with radiation therapy was associated with a higher number of acute skin reactions, this did not appear to translate into increased long term morbidity. The percentage of patients ambulating without assistive devices and with mild or no pain was 84%. Careful attention to the techniques of radiation therapy may have a significant impact on minimizing acute and long term complications of limb sparing treatment for extremity soft tissue sarcoma. PMID- 1938559 TI - Ewing's sarcoma: local tumor control and patterns of failure following limited volume radiation therapy. AB - Sixty children with localized osseous Ewing's sarcoma were treated between 1978 and 1988 with induction chemotherapy (cyclophosphamide, adriamycin), irradiation and/or surgery, and 10 months of maintenance chemotherapy (cyclophosphamide, adriamycin, dactinomycin, vincristine). Following induction chemotherapy, 43 patients received primary radiation therapy to limited radiation volumes defined by post-chemotherapy residual soft tissue tumor extension and initial osseous tumor extent. Irradiation was defined as low dose at 30-36 Gy (median 35 Gy) for 31 cases with objective response to induction chemotherapy and high dose at 50-60 Gy (median 50.4 Gy) for 12 patients with poor response to induction chemotherapy or with tumors greater than or equal to 8 cm. Overall event-free survival at 5 years is 59% and local tumor control is 68%. Initial failures have been local (12), simultaneous local and distant failures (7), and distant (6). In the surgical resection group, 14 patients had complete resection without radiation therapy, and 3 patients had microscopic residual plus 35-41 Gy; 100% local control has been maintained. In 43 patients with primary radiation therapy group, local tumor control is 58% (p = .004). Despite limited radiation volume, 18/19 local failures occurred centrally within the bone, well within the radiation volume. Imaging response to induction chemotherapy predicted local tumor control in the radiation therapy group: 62% with complete response/partial response versus 17% with no response/progressive disease (p less than 0.01). Local tumor control related strongly to primary tumor size in the radiation therapy group; among 31 cases receiving 35 Gy, local tumor control is 90% for lesions less than 8 cm versus 52% for tumors greater than or equal to 8 cm (p = .054). The central pattern of local failure in this experience suggests the effectiveness of limited radiation volume. The overall local tumor control rate following the tested dose level of 35 Gy appears to be inadequate, although results in selected cases with tumors less than 8 cm in greatest tumor dimension indicate potential efficacy in a yet limited experience. PMID- 1938560 TI - Local control and function after twice-a-day radiotherapy for Ewing's sarcoma of bone. AB - Between February 1982 and December 1987, 39 patients with Ewing's sarcoma of bone have been treated at the University of Florida with a twice-a-day radiotherapy regimen to their primary lesion, 35 with radiation alone and 4 with a combination of radiation and surgery. Although three separate systemic regimens were used (standard risk, 1982-1987 [SR-1]; high-risk, 1982-1984 [HR-2]; and high-risk, 1985-1987 [HR-3]), the radiotherapy regimen remained constant through the years of the study. Those patients whose soft-tissue mass completely regressed after induction chemotherapy received 5040 cGy (as did patients with no soft-tissue mass at diagnosis), those who had 50% or greater resolution of the soft-tissue mass received 5520 cGy, and those who had less than 50% regression of the soft tissue mass or progressive disease during induction chemotherapy received 6000 cGy. All patients were treated with 120 cGy twice a day and a 6-hr separation between fractions. Thirteen patients also received 800 cGy of total body radiotherapy (TBI) 1 to 3 months after local radiotherapy as part of their systemic treatment. In the 33 patients treated with radiotherapy alone who were eligible for local control analysis, there have been three local failures to date, all within the first 21 months after diagnosis. The 5-year local control rate was 88% for SR-1, 80% for HR-2, and 92% for HR-3. Local control was not related to total dose, but by design, the patients with the largest lesions and the poorest response to chemotherapy had the highest doses. In the 20 patients presenting with extremity primary lesions, there have been no pathologic fractures. In patients evaluated for limb function, the late effects have been minimal. The twice-a-day regimen used appears to produce good local control rates with improved long-term function as compared with once-a-day regimens. PMID- 1938561 TI - Radiotherapy in the management of cutaneous epidemic Kaposi's sarcoma. AB - Between June 1986 and December 1988, we treated 149 patients who had AIDS-related epidemic Kaposi's sarcoma with cutaneous irradiation. According to Mitsayasu's staging, 34 patients (23%) had Stage I disease, 82 (55%) Stage II, 0 Stage III, and 33 (22%) Stage IV. Fifty-eight patients (39%) had previously presented with one or more opportunistic infections. Ninety-four patients (63%) had received previous treatment of their Kaposi's sarcoma: 85 (57%) with interferon and 43 (29%) with vinblastine. Among the 149 patients, we treated 88 (59%) with extended cutaneous irradiation using 4- and/or 8-MeV electron beam energy and 61 patients (41%) with localized irradiation using 45-kVp x-ray energy. The total prescribed dose was 30 Gy: 20 Gy in 2 weeks (2.5 Gy/fraction, 4 times/week), followed by 2 weeks of no irradiation, and then 10 Gy in one week by the same dose schedule. Twenty patients (13%) with edema of the lower limbs were treated using 4-Mv photon therapy with bolus. Of the 131 evaluable patients, 63% achieved a complete remission (CR) and 30% a partial remission (PR) after a mean period of 1.5 months (range: 0.5-3 months). The clinical disease stage, anatomic site, and irradiation technique did not significantly influence the remission rates, although we noticed a higher CR rate when localized irradiation was used (71% vs 55.5% for localized and extended irradiation, respectively; p = 0.08). The overall tolerance was acceptable. Complications were severe epidermitis with skin ulcerations (8% of patients), exudative epidermitis (26%), dry epidermitis (60%), and varying degrees of erythema (6%). Of the 87 patients whose AIDS remained relatively clinically stable during the observation period, recurrences occurred in 56 (64%) after an average of 5.5 months (range: 1.5-12 months). We conclude that radiotherapy is useful and can be recommended as a palliative treatment to relieve pain and physical discomfort or to achieve cosmetic improvements for patients with epidemic Kaposi's sarcoma. We also conclude that radiotherapy is most beneficial in the early stages of disease, when localized treatment is practical. PMID- 1938562 TI - Early and late effects of mitomycin C and continuous low-dose-rate irradiation on the mouse skin and soft tissues of the leg. AB - The early and late effects of combined mitomycin C and continuous low-dose-rate irradiation (CLDRI) on the skin and soft tissues were studied in the C3Hf/SED mice. Localized CLDRI of the hind leg at 0.028 Gy/min with and without mitomycin C was delivered using a 137Cs laboratory irradiator. Mitomycin C at 6 mg/kg was given by continuous infusion through intraperitoneally implanted osmotic mini pumps during CLDRI. Acute skin reaction was scored from days 13 to 30 and late skin contraction and leg contracture were measured at days 90, 180, 270, and 360 after treatment. Mitomycin C increased the early skin reaction following CLDRI; at a dose of 60 Gy, the dose effect factor was approximately 1.1. However, there was no significant enhancement of late skin contraction or leg contracture by mitomycin C. Our results suggest that mitomycin C can be combined with low-dose rate brachytherapy without a significant increase in early or late damage to the skin and soft tissues. PMID- 1938563 TI - The accelerated repopulation of a murine fibrosarcoma, FSA-II, during the fractionated irradiation and the linear-quadratic model. AB - Radiation response of a spontaneous mouse fibrosarcoma, FSa-II, to various fractionated doses was studied in vivo together with single dose cell survival curves. Early generation isotransplants were used. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Lung colony and TD50 assays were used to determine cell survival. Surviving fractions were determined following fractionated irradiations of 1.0 to 5.0 Gy each per fraction with interfractional time intervals of 4 hr. The alpha/beta ratio based on fractionated irradiations was 8.8 Gy for aerobic FSa-II tumor cells and flexure dose was less than 1.3 Gy. Multiple fractions of 5.0 Gy each given with 4, 12, and 24 hr intervals showed an increase in survival with increasing interfractional time interval, suggesting a rapid repopulation of tumor cells between fractions; namely, cell doubling time was shortened between fractions after the first 5.0 Gy doses. These results indicated that tumor cell repopulation is a critical factor in the fractionated radiotherapy. Linear-quadratic model was fitted to single dose survival data. Single dose survival curve of aerobic FSa-II tumor cells following lung colony assays which allowed determination of minimal survival of approximately 3.0 x 10( 3) showed that alpha, beta, and alpha/beta ratios were 0.25 Gy-1, 0.048 Gy-2, and 8.47 Gy, respectively. Single dose survival curve of the same aerobic cells determined by both lung colony and TD50 assays to a survival level of approximately 3.0 x 10(-6) demonstrated that alpha, beta, and alpha/beta ratios were 0.375, 0.0127, and 29.5, respectively. Similar determination for hypoxic FSa II tumor cells showed that alpha, beta values were smaller whereas the alpha/beta ratio was much larger than for aerobic cells. The oxygen enhancement ratio calculated by the alpha/beta ratios was greater than 3.0. PMID- 1938564 TI - 5-[123I]iodo-2'-deoxyuridine in the radiotherapy of an early ascites tumor model. AB - The extreme biological toxicity of Auger emitters is caused by the decay associated, highly localized deposition of energy. The antineoplastic capability of an Auger-electron emitter, iodine-123, incorporated into the thymidine analog, 5-iodo-2'-deoxyuridine (IUdR) was evaluated in an intraperitoneal (i.p.) murine ovarian tumor (MOT) in female C3HeB/FeJ mice. Total doses of 0.37 to 8.88 MBq (10 240 microCi) 123IUdR were administered i.p. in five equally divided fractions at 24, 28, 32, 36, and 40 hr after the i.p. inoculation of 0.5 to 1.6 x 10(6) tumor cells per mouse. Control tumor-bearing animals were injected with identical volumes of saline at 4-hr intervals. Biodistribution studies demonstrated a distinct and localized uptake of 123IUdR in the MOT cells (1% of the injected dose was associated with MOT cells 24 hr after the last injection), whereas in animals without tumor there was no radioactivity associated with the peritoneal cells. Analogous results were obtained from scintigraphic images where the focal area of abdominal activity persisted only in MOT-bearing mice while it cleared from the abdomen of the controls. The 50% survival (median survival) of the control group was 19 days for an inoculum of 1.6 x 10(6) MOT cells per animal, whereas the median survival of MOT-bearing animals treated with 123IUdR increased by 11 days for the highest administered dose (8.88 MBq, 240 microCi) and resulted in a 20% absolute survival at 7 weeks. Statistically significant absolute survival prolongation was found with all of the total administered doses. The prolongation of both median and absolute survival time of the tumor-bearing animals treated with 123IUdR conclusively indicates the substantial antineoplastic activity of the Auger-electron emitter iodine-123. PMID- 1938566 TI - Significance of additive heat effect in the therapeutic gain factor in combined hyperthermia and radiotherapy: murine tumor response and foot reaction. AB - The thermal enhancement ratio (TER) and therapeutic gain factor (TGF) were evaluated for combined hyperthermia and radiation treatments of a murine fibrosarcoma, FSa-II. The TER is the ratio of the radiation dose that induces a given reaction without hyperthermia to that with hyperthermia. The TGF is defined as the ratio of TER for tumor response to TER for normal tissue response. Tumors in the subcutaneous tissue of the right foot were irradiated with graded radiation doses when they reached an average diameter of 6 mm (110 mm3). Hyperthermia was given by immersing animal feet in a constant temperature water bath 10 min before or after irradiation. The tumor growth time to reach 500 mm3 was obtained for each tumor and the median tumor growth time was calculated for each treatment group. For the normal tissue study, the non-tumor bearing murine foot was treated, as was the tumor, and the foot reaction was scored after treatment, according to our numerical score system for radiation damage, until the 35th post-treatment day and averaged. Using the fraction of animals showing a given average foot reaction score in a treatment group, the RD50, or the radiation dose to induce the given foot reaction or greater, was calculated. A single heating at 45.5 degrees C for 10 min and a step-down heating (first heat at 45.5 degrees C for 10 min immediately followed by the second heat at 41.5 degrees C for 60 min) prolonged the tumor growth time, indicating that hyperthermia per se resulted in some cell killing. The prolongation was greater following step-down heating than following single heating. These heat treatments alone induced no noticeable heat damage on the foot, but decreased the threshold dose observed on the radiation dose response curves for the foot reaction. Accordingly, TER and TGF were evaluated with or without normalizing this thermal effect. TER's for both tumor and foot responses without normalization were greater than the TER's after normalization and decreased with increasing radiation dose (between 1.9 and 7.1 or greater for tumor and between 1.3 and 4.3 or greater for foot reaction), whereas the normalized TER's were relatively constant (between 1.6 and 1.7 for tumor and between 0.7 and 1.5 for foot reaction). TGF's without normalization were greater than those obtained after normalization. The former was large at small doses and decreased with increasing radiation dose (between 1.5 and 4.0 or greater), whereas the latter was within 0.8 and 1.3 and relatively independent of radiation dose.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1938565 TI - Radiation sensitivity of human B-lineage lymphoid precursor cells. AB - We studied the radiation sensitivity of eight immunophenotypically distinct B lineage lymphoid precursor cell (LPC) lines of acute lymphoblastic leukemia (ALL) or fetal liver origin corresponding to discrete developmental stages of human B cell ontogeny. The radiation sensitivity of B-lineage LPC showed a temporal association with the distinct stages of development. FL112 and FL114 fetal liver pro-B cells (Stage 0 B-lineage LPC) with germline immunoglobulin heavy chain (IgH) genes but rearranged T-cell receptor gamma (T gamma) genes (DO of FL112 = 80.3 cGy, DO of FL114 = 50.2 cGy), REH ALL pre-pre-B cells (Stage I B-lineage LPC) with rearranged IgH and T gamma genes (DO = 66.1 cGy), and NALM-6 ALL pre pre-B/pre-B cells (Stage II B-lineage LPC) (DO = 50.5 cGy) corresponding to the earliest three stages of human B-lymphocyte development were the most radiation sensitive B-lineage LPC populations. By comparison, KM-3 ALL pre-B (Stage III B lineage LPC) (DO = 194.7 cGy), HPB-NULL ALL pre-B (Stage IV B-lineage LPC) (DO = 134.6 cGy), and sIgM+ RAJI/NAMALWA early B (Stage Va/b B-lineage LPC) cell lines (DO of RAJI = 144.0 cGy, DO of NAMALWA = 165.5 cGy) corresponding to the later stages of human B-lymphocyte development were much more radiation resistant. These results indicate that the radiation sensitivity of B-lineage LPC decreases during maturation within the B-lineage lymphoid precursor pathway. By comparison, the S-phase index (% of S-phase cells as determined by DNA flow cytometry) or proliferation index (% S + G2M), cellular protein content, intracellular glutathione (GSH) level, glutathione-S-transferase (GST) activity, intracellular pH, or free cytoplasmic calcium concentration did not correlate with the radiation sensitivity of the B-lineage LPC. PMID- 1938567 TI - One versus four heat treatments in combination with radiotherapy in metastatic mammary carcinoma. AB - To optimize the total and the weekly number of heat treatments to be combined with a conventional radiotherapy course, a study was designed on a 75-year-old woman with 40 cutaneous nodules of metastatic mammary carcinoma. All nodules were individually irradiated by means of orthovoltage radiation to doses of 36 to 44 Gy, given in 20 equal fractions in 4 weeks. The nodules were randomly assigned to receive radiotherapy alone or radiotherapy combined with one or four heat treatments. Eight lesions were left untreated as a control arm of the systemic therapy (endocrine manipulation). Hyperthermia at a minimum temperature of 43 degrees C was applied for 45 min once per week for four times or only once, during a course of radiotherapy. Percent mean diameter of the treated lesions continuously decreased, reaching a minimum of 25-30% of the initial value after 4 months from the beginning of treatment with no difference between the three arms. After this period, tumors treated with radiotherapy alone or radiotherapy plus one heat treatment started to regrow, whereas those treated with radiotherapy plus four heat treatments continued to decrease slowly. The actuarial analysis of freedom from local progression showed a trend of improvement of response duration with four hyperthermic treatments with respect to radiotherapy alone or combined with one hyperthermic treatment. PMID- 1938568 TI - Optimal scheduling of biologically targeted radiotherapy and total body irradiation with bone marrow rescue for the treatment of systemic malignant disease. AB - A mathematical model analysis is used to address the question of optimal scheduling of combined treatments consisting of biologically targeted radiotherapy (BTR), total body irradiation (TBI), and bone marrow rescue. Radiation effects on normal tissue are described using an extension of the LQ model. Tumor effects are described using a simple model that allows for radiation induced sterilization and exponential proliferation of tumor cells, a proportion of which completely escapes the effects of targeted radiotherapy. The effect on a tumor cell population of a set of treatment schedules, composed partly of targeted radiotherapy and partly of fractionated external beam irradiation, are calculated. Treatment schedules are chosen to be biologically equivalent, for a "late responding" organ, to a fractionated TBI schedule of 7 fractions of 2 Gy. The tumor effects of the treatment schedules depend on the specificity of targeting, represented by the ratio of initial dose-rate for the tumor cells to that in the dose-limiting organ, and the heterogeneity of targeting, represented by the proportion of tumor cells that escape irradiation by targeted radiotherapy. The main mechanism determining optimal combinations is an overkill of effectively targeted tumor cells. Treatment regiments consisting of targeted radiotherapy alone fail, due to the unimpeded growth of those tumor cells that escape targeted irradiation. Optimal schedules almost invariably consist of elements of both BTR and TBI. Although it is recognized that the model is simplistic in a number of respects, these findings provide support for the clinical use of integrated BTR, TBI, and bone marrow rescue for the treatment of systemic malignant disease. PMID- 1938569 TI - Preoperative and postoperative irradiation of soft tissue sarcomas: effect of radiation field size. AB - For the treatment of soft tissue sarcomas it has frequently been staged but not quantitatively demonstrated, that the volume irradiated is smaller when irradiation is given preoperatively as compared to postoperatively. In this study the field size used for preoperative irradiation was compared with that necessary in the same patient had the radiation been given postoperatively. Twenty-six patients with soft tissue sarcomas of the extremity, groin, and shoulder girdle who had received preoperative irradiation were resimulated following surgery to determine the size of the postoperative field. The simulation was performed by a physician not involved in the preoperative treatment planning. Preoperatively a radial margin of 5 cm around the tumor was used for low and intermediate grade and 7 cm for high grade sarcomas. Postoperatively the same margins were used but around the surgical field. Twelve patients underwent a wide resection and 14 patients a resection followed by vascularized tissue transfer to the surgical bed. The median follow-up was 22 months (range 13-46). No local recurrences and two cases of distant metastasis were observed. Independently of surgical procedure and tumor grade, the size of the preoperative radiation field and number of joints included in the field were significantly smaller than that of postoperative radiation (p less than 0.001). In two patients preoperatively and four patients postoperatively, the radiation field involved the whole circumference of the limb. Provided that equivalent radiation time-dose-fraction parameters are used and that the complication rate is proportional to the radiation field size, late complications may be less after preoperative irradiation than after post-operative irradiation. PMID- 1938570 TI - Primary subglottic cancer: results of radical radiation therapy. AB - Between October 1964 and December 1985, six patients with primary squamous cell carcinoma of the subglottis were treated with radical radiation therapy at the University of Florida. The disease was staged as Tis (one patient), T2N0 (two patients), and T4N0 (three patients). Local control was achieved with irradiation in four patients (66%) who were observed for 3.5, 4, 4, and 5 years after radiation therapy. Two patients whose tumors recurred at the primary site underwent salvage laryngectomy, which was successful in one patient. PMID- 1938571 TI - Clinical implications of I-125 dosimetry of bone and bone-soft tissue interfaces. AB - The dose to bone from I-125 photon interactions is expected to be approximately five times greater than the dose to soft tissue for the same photon fluence because of the dominance of the photoelectric effect. However, adverse clinical effects are not observed for I-125 implants near bone. Both the strong absorption of I-125 photons in bone and the narrowness (about 10 mu) of the high dose transition zone at a bone-soft tissue interface act to limit the volume of radiation sensitive tissue in the high dose region. Examples of calculated implant dose distributions in bone and in soft tissue cavities in bone are presented. Radiobiological measurements are consistent with the theoretical interface calculations. Calculation of the macroscopic dose distribution uses a recently measured radial dose function, while at the bone-soft tissue interface an analytic theory of the transition zone that is applicable to regular shaped cavities is used. Radiobiological experiments comparing cell survival for cells irradiated with 70 kvP X rays at Al-water and polystyrene-water interfaces are consistent with the transition zone calculations. PMID- 1938572 TI - Optimization of high dose-rate cervix brachytherapy; Part I: Dose distribution. AB - Computer controlled high dose-rate (HDR) brachytherapy afterloading machines are equipped with a single, miniaturized, high activity Ir-192 source that can be rapidly moved in fine increments among several channels. Consequently, by appropriate programming of source dwell positions and times, the dose distribution can be optimized as desired. We have explored the optimization potential of this new technology for two applications: (a) cervix brachytherapy, and (b) transvaginal irradiation. Cervix brachytherapy with a gynecologic ring applicator was simulated by 48 sources of relative activities ranging from 0.17 to 1.00 that were equally distributed between the tandem and the ring. The results confirmed that the optimized distribution of physical doses are superior to those achievable with standard brachytherapy sources and applicators. For example, with five-point optimization, the relative dose-rate in the rectum was only 47% of that in point A; for standard application the dose rate was 47% higher. For transvaginal application 27 sources of relative activities between 0.07-0.79 were placed in the ring and a single source of unit strength in the tandem. Using dose distribution homogeneity as an optimization criterion, the results (+/- 2.5%) were again superior to those obtained for commonly used double ovoid (+/- 15%), linear cylinder (+/- 27%), or a "T" source (31%). PMID- 1938573 TI - Electron beam modifications for the treatment of superficial malignancies. AB - For the treatment of superficial tumors, the surface dose should be high; unfortunately, because of pronounced dose buildup in low energy electron beams, their efficacy for such treatment is reduced. Electron beams can be modified by placing a low atomic number material called a beam spoiler in the beam. In general, the surface dose is a function of electron energy, source to surface distance, field size, thickness of beam spoiler, distance of beam spoiler from surface, atomic number of beam spoiler, and angle of the beam. The effects of these parameters are evaluated with respect to surface dose, bremsstrahlung dose, and field size changes for small fields at standard SSD and electron energies from 6 to 17 MeV. It was found that the use of a beam spoiler can generally increase the surface dose to values exceeding 90% of the maximum buildup value while maintaining a bremsstrahlung dose less than 3%. Changes in field size related to the placement of the beam spoiler were considerable in some cases. PMID- 1938574 TI - Musculoskeletal oncologic imaging. AB - A cost efficient algorithm is presented for workup of musculoskeletal tumors. This is given within the framework of requirements for surgical staging. Considerations regarding both percutaneous and open biopsy are outlined. The advantages as well as limitations of MR imaging are stressed. PMID- 1938575 TI - Integration of multimodality imaging data for radiotherapy treatment planning. AB - This paper describes computational techniques to permit the quantitative integration of magnetic resonance (MR), positron emission tomography (PET), and x ray computed tomography (CT) imaging data sets. These methods are used to incorporate unique diagnostic information provided by PET and MR imaging into CT based treatment planning for radiotherapy of intracranial tumors and vascular malformations. Integration of information from the different imaging modalities is treated as a two-step process. The first step is to determine the set of geometric parameters relating the coordinates of two imaging data sets. No universal method for determining these parameters is appropriate because of the diversity of contemporary imaging methods and data formats. Most situations can be handled by one of the four different techniques described. These four methods make use of specific geometric objects contained in the two data sets to determine the parameters. These objects are: (a) anatomical and/or fiducial points, (b) attached line markers, (c) anatomical surfaces, and (d) outlines of anatomical structures. The second step involves using the derived transformation to transfer outlines of treatment volumes and/or anatomical structures drawn on the images of one imaging study to the images of another study, usually the treatment planning CT. Solid modelling and image processing techniques have been adapted and developed further to accomplish this task. Clinical examples and phantom studies are presented which verify the different aspects of these techniques and demonstrate the accuracy with which they can be applied. Clinical use of these techniques for treatment planning has resulted in improvements in localization of treatment volumes and critical structures in the brain. These improvements have allowed greater sparing of normal tissues and more precise delivery of energy to the desired irradiation volume. It is believed that these improvements will have a positive impact on the outcome of radiation therapy. PMID- 1938576 TI - Out on a limb on sarcomas. PMID- 1938577 TI - The four S's of Ewing's sarcoma. PMID- 1938578 TI - Race and survival from intracranial ependymomas in children. PMID- 1938579 TI - Erratum for 'Presidential address: systemic radiotherapy--the new frontier' by S. Order. PMID- 1938580 TI - Psychoanalytic education: a model for the 1990s. PMID- 1938581 TI - The creative person as maverick. AB - The innate talents that are the essence of creativity are associated with a particular type of character structure. The child's creative potential has to be supported by the infantile milieu, which also happens to have a characteristic stamp. Within this context of personality configurations and developmental antecedents associated with creative ability, there can be considerable variation. I am not postulating a specific or stereotypic creative character. There are, however, certain qualities that can be found in various character types (and can even exist alongside psychopathology) that are often found in creative scientists and perhaps artists as well. I believe the maverick often possesses these character traits and many of the scientists I have had the opportunity of treating proudly considered themselves mavericks. The creative personality is characterized by paradoxes; these cast it in the maverick mold. Possessors of this personality belong and do not belong. They do not break the rules but bend them a little. They are nonconformists but not rebels. They display many features that do not seem to belong together. The paradoxical qualities that dominate the creator's personality and behavior are the outcome of a certain fluidity of character and ego boundaries. The creative process involves a broad range of functioning and traverses various levels of the psyche, frequently reaching down to the very earliest, primary-process-oriented parts of the self. Ego boundaries, in turn, can become quite fluid and permeable, even though they are ordinarily firmly established and well structured. It is this broad spectrum, a prominent feature of the creative process (Giovacchini, 1965, 1971, 1981), that has been often confused with psychopathology. These paradoxical elements are the outcome of an infantile environment that has provided considerable gratification. Again the early milieu of creative personalities may be extremely varied, but there has always been some person or persons who have had a considerable emotional investment in the child. As the developing psyche incorporates and introjects these gratifying and security-establishing experiences, they become amalgamated into the self-representation. In the face of adversity, they provide confidence and reassurance and allow the creator to soothe him- or herself when upset by inner tension. Consequently, creative scientists do not depend so much on the outer world as they do on inner resources. One scientist told me that he could not understand how anyone could ever be bored. Even if he were denied access to his work, he could always find something interesting to do or explore.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1938582 TI - A psychophysiologic perspective on affect and psychotherapy. PMID- 1938583 TI - Brain and self: toward a neuropsychodynamic model of ego autonomy and personality. AB - Principles derived from neuropsychology can begin to be applied to the development of heuristic models of complex psychological processes and can thereby contribute to theories of personality and psychopathology. Applications of neuropsychological concepts to the problems of self-knowledge, ego autonomy, and personality integration are discussed. Special reference is made to the role of the frontal lobes in the recursive modulation of behavior and to the verbal functions of the left hemisphere in self-awareness and self-control. Caution against a narrow localizationist conceptualization of human behavior is urged, and suggestions for interdisciplinary rapproachment are offered. PMID- 1938585 TI - Infantile sexuality revisited: the agony and ecstasy of the mother-infant couple. AB - This article explores the relationship between primitive somatopsychic states of excitation and ecstasy in the early infant-mother nursing dyad and similar states of excitation and ecstasy occurring in sexual intercourse of the adult couple. Clinical material demonstrates the close link between early infantile breast experience and adult genital arousal, illustrating aspects of success or failure in integration of body-sensation states as the core of the self. Failure to master primitive somatopsychic excitations in infancy is held to be relevant in understanding intolerance of excitation in certain adult sexual dysfunctions. This understanding is elaborated to include intolerance of emotional arousal (excitement) in the "analytic intercourse" as well. Maternal functions of containing and modulating excitation and arousal states are proposed as therapeutic interventions on the model of the mother as a "container" for infantile anxieties and excitement, employing empathic identification with her baby in the form of "reverie." "Holding" capacities in mother and therapist facilitate the possibility of integration of psychic and somatic states, allowing a potential for the partners to experience excitement in the interest of creative intercourse, both mental and physical. PMID- 1938584 TI - Posttraumatic stress disorder after sexual assault: its psychodynamics and treatment. AB - Sexual assault as a major psychological trauma and a crime of violence evokes immediate symptoms of posttraumatic stress and, for many victims, long-term posttraumatic psychological sequelae. The victim, as the recipient of the rapist's anger and need to control, experiences terror, fear of death, and helplessness. This results in classic posttraumatic symptoms of haunting, intrusive recollections, numbing or constriction of feelings and focus, and increased arousal. When this psychological trauma is not integrated, anxiety, depression, phobias, impaired sexual and social adjustment, negative self-image, and diminished capacity to enjoy life follow. Concepts of posttraumatic stress are reviewed and a definition of sexual assault is offered. The posttraumatic stress response to sexual assault is considered under the phases of response and symptoms, followed by the psychodynamics of this particular psychic trauma. A brief overview of treatment is outlined. PMID- 1938586 TI - Sandor Ferenczi on female sexuality. PMID- 1938587 TI - Freud and the mighty warrior. AB - This essay traces a prominent facet of Freud's personality, his being a "mighty warrior" throughout his life. This aspect of his character evolved as a reaction formation against his submissive father and as an identification with his more aggressive mother. He first tried it out in his highly ambivalent relationship to his nephew John, who was one year older. In his childhood play, Freud identified with certain military heroes, such mighty warriors as Napoleon, Hannibal, Alexander the Great, and Massena. As he grew older he shifted from military heroes to other great men including Goethe, Shakespeare, and finally Moses. He substituted these men as ego ideals in place of his father about whose stature he felt disillusioned. He far surpassed his father in his life achievements and yet managed to maintain an even-handed, respectable relationship with him until he died in 1896. His mother all but worshipped Sigmund but also demanded that he achieved the maximum in whatever he did. He had to earn her love by an outstanding performance but always wanted to feel unconditionally loved. His mighty warrior attitude developed into an important part of its personality. It protected him from feelings of helplessness and inadequacy and made him into an outstanding leader of the psychoanalytic movement. PMID- 1938588 TI - The role of the transference in the Wolf Man case. AB - The Wolf Man case offers the last detailed record of Freud's work and his appraisal of the therapeutic vectors in analysis, including the transference. The Wolf Man, Sergius Pankejeff, died on May 7, 1979 in Vienna in a municipal institution at the age of 92. Kurt Eissler (1980) reported in the International Journal of Psycho-Analysis that although his mental faculties were in a decline, his last two years of life were peaceful (pp. 104-105). This essay has attempted to demonstrate that Freud's therapeutic emphases in 1914 were centered on memory revival sufficient to allow for reconstruction to be made that would explain the neurotic conflicts. The transference was in fact viewed as a facilitator in the revival of the significant childhood memories. PMID- 1938589 TI - Jung's concept of individuation. PMID- 1938590 TI - The deathly embrace: the fate of symbiosis in marriage. PMID- 1938591 TI - A comment on "A psychophysiologic perspective on affect and psychotherapy" by Herbert S. Gross, M.D. and Kenneth Fligsten, M.D. PMID- 1938592 TI - Case report. Myofacial pain. PMID- 1938593 TI - Philosophy underlying the use of the Crozat appliance. PMID- 1938594 TI - Case report. Class III malocclusion. PMID- 1938596 TI - Morphometrical analysis of structural abnormality of tubular tumors of the stomach with image processing. AB - Four indices, index of tubular density, index of dispersion of tubular size, degree of complexity of tubular shape and frequency of complex-shaped tubuli, were defined to quantify the structural abnormalities of gastric tumors in morphometrical analysis by image processing. The values of each index corresponded well with the degree of each structural abnormality found pathologically. These indices were considered to be valid for representing their respective structural factors. There were significant differences among the mean values of the scores calculated by a formula using all 4 indices of benign tubular adenoma, borderline lesion and well-differentiated type tubular adenocarcinoma (P less than 0.05). Therefore, the discriminant formula was considered to be valid for integrating these indices and for representing structural abnormality of gastric tubular tumors. PMID- 1938595 TI - Effects of glucocorticoids and calcitonin on parathyroid hormone-related protein (PTHrP) gene expression and PTHrP release in human cancer cells causing humoral hypercalcemia. AB - Glucocorticoids are widely used for the treatment of malignancy-associated hypercalcemia to delay the occurrence of an escape phenomenon inherent in calcitonin therapy. Using parathyroid hormone-related protein (PTHrP)-producing squamous carcinoma cells (T3M-1 and EC-GI) established in our laboratory, we investigated the in vitro effects of glucocorticoids and calcitonin on PTHrP mRNA expression in the cells and release of PTHrP into the culture medium. The PTHrP gene was constitutively expressed in the logarithmic growth phase in both squamous carcinoma cell lines. When these cells became superconfluent, PTHrP mRNA expression was greatly diminished in T3M-1 cells but was not distinctly diminished in EC-GI cells. Hydrocortisone inhibited the PTHrP mRNA expression in T3M-1 cells and EC-GI cells in a dose-dependent manner. In accordance with the decreased expression of PTHrP mRNA, the release of immunoreactive as well as bioactive PTHrP also decreased in the conditioned medium of glucocorticoid treated cells. The minimal effective concentration of prednisolone was about 10( 7) M, which is readily attainable in the serum of patients treated with the agent. Calcitonin and indomethacin did not affect the PTHrP mRNA expression or PTHrP release into the medium. Calcitonin did not modulate the hydrocortisone induced inhibition of PTHrP production. These in vitro findings suggest that the combined use of glucocorticoids and calcitonin plays a beneficial role in the treatment of malignancy-associated hypercalcemia, since the steroid hormone can suppress PTHrP mRNA expression and release of bioactive PTHrP in certain PTHrP producing tumors. PMID- 1938597 TI - Localization of acidic and basic fibroblast growth factor mRNA in human brain tumors. AB - Acidic and basic fibroblast growth factors (aFGF and bFGF) are closely related peptide mitogens acting on both mesoderm- and neuroectoderm-derived cells, including fibroblasts, endothelial cells and glial cells. In order to identify the expression of mRNAs for these growth factors, in situ hybridization using human aFGF and bFGF RNA probes was performed in 24 human brain tumors. The mRNAs for aFGF and bFGF were expressed in the cells of various tumors (1/1 and 1/1 astrocytoma, 2/2 and 2/2 anaplastic astrocytomas, 6/6 and 6/6 glioblastomas, 4/4 and 4/4 meningiomas, 3/3 and 3/3 schwannomas, 1/2 and 1/2 pituitary adenomas, 4/4 and 4/4 metastatic carcinomas, 0/1 an 0/1 hemangioblastoma, 0/1 and 0/1 craniopharyngioma) and were also detected in endothelial cells and surrounding neuronal cells of brain tumors. These results suggest the possibilities that aFGF and bFGF contribute to the uncontrolled growth of tumor cells and the proliferation of endothelial cells in autocrine and paracrine manners, and that the expression of mRNAs for these growth factors in the surrounding neuronal cells results in enhancement of tumor growth. PMID- 1938598 TI - Augmentation and suppression of release of tumor necrosis factor from macrophages by negatively charged phospholipids. AB - We recently reported that some lipid species of cell membranes and lipoproteins induced the growth of peripheral macrophages. In this study, the effects of phospholipids on tumor necrosis factor (TNF)-releasing activity of macrophages were examined. Ten to 20 micrograms/ml of cardiolipin, which is a suboptimal concentration for macrophage growth-stimulation, augmented macrophage TNF release triggered by lipopolysaccharide (LPS) in vitro. This priming effect appeared with 1 day of preincubation and was still potent on day 3, whereas the priming effect of interferon-gamma (IFN-gamma) peaked at 3 h and then gradually decreased. In contrast, a high concentration of cardiolipin (40 micrograms/ml) which is optimal for the induction of macrophage growth, completely suppressed LPS-triggered TNF release from not only untreated macrophages but also IFN-gamma-primed macrophages. The suppressive effect was potent even with 3 h preincubation, was still potent on day 3, and was not abolished by indomethacin. Cardiolipin had scarcely any effect on the triggering activity of LPS. Similar augmentative and suppressive activities were observed in peroxidized phosphatidylserine, which is also highly active in inducing macrophage growth, but was not found in native phosphatidylserine, which is less active in inducing macrophage growth, but was not found in native phosphatidylserine, which is less active, nor in phosphatidylcholine, which is an inactive species toward macrophage growth. These results suggest that lipids may be important endogenous factors in regulating both activation and growth states of peripheral macrophages. PMID- 1938599 TI - Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and tumor-infiltrating lymphocytes activated by PSK. AB - The protein-bound polysaccharide PSK was tested for the ability to induce in vitro autologous tumor killing (ATK) activity in human cancer patients. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) demonstrated various levels of cytotoxicity against autologous, freshly isolated tumor cells. When PBL and TIL were cultured overnight with PSK, ATK activity was induced in previously non-reactive cases and augmented in previously reactive samples. The PSK effect was observed with PSK concentrations of 10-100 micrograms/ml that could be obtained in the blood of cancer patients who received standard oral administration of PSK. The manifestation of PSK-induced ATK required active cell metabolism and RNA and protein syntheses, but not DNA synthesis of lymphocytes. PSK-induced enhancement of ATK was not abrogated by monoclonal antibodies (mAb) directed against interferon (IFN) alpha or IFN gamma. In addition, mAb that neutralized interleukin-2 (IL-2) or mAb reactive with alpha chain or beta-chain of IL-2 receptors (IL-2R) had no effect on PSK-induced ATK activity. Supernatants from PSK-stimulated lymphocyte cultures did not induce ATK. Cell fractionation experiments revealed that CD3-CD16+ large granular lymphocytes (LGL) and/or CD3+CD16- T lymphocytes were responsible for both spontaneous and PSK-induced ATK. PSK-activated LGL, but not T lymphocytes expressed lysis of fresh allogeneic tumor cells. These results indicate that PSK activates PBL and TIL to exhibit ATK independently of IL-2/IL-2R systems. PMID- 1938600 TI - Cytotoxic effects of vitamin A in combination with vincristine, daunorubicin and 6-thioguanine upon cells from lymphoblastic leukemic patients. AB - We studied whether isotretinoin potentiated the effects of vincristine (VCR), daunorubicin (DNR), and 6-thioguanine (6-TG) against cells obtained from 24 patients with acute lymphoblastic leukemia (ALL). Treatment with 5 micrograms/ml isotretinoin alone resulted in a leukemic cell survival of 82% +/- 28.1%. So isotretinoin is toxic to ALL cells. Dose-response curves were obtained for VCR, DNR and 6-TG in the presence and absence of isotretinoin Isotretinoin showed additive leukemic cell kills in combination with VCR and DNR. When corrected for cell kill by isotretinoin alone, it appeared that isotretinoin did not significantly enhance leukemic cell kills by VCR, DNR and 6-TG. No differences were found between samples from patients at initial diagnosis and at relapse with respect to cell kill by isotretinoin alone and with respect to a possible synergistic effect of isotretinoin and the cytostatic drugs. It is concluded that isotretinoin has additive antileukemic effects in combination with VCR or DNR. However, isotretinoin does not potentiate the antileukemic effects of VCR, DNR and 6-TG against leukemic cells obtained from patients with ALL. PMID- 1938601 TI - Expression of cripto, a novel gene of the epidermal growth factor family, in human gastrointestinal carcinomas. AB - The expression of mRNA for cripto gene, a novel transforming gene of the epidermal growth factor family, was examined in 20 alimentary tract carcinoma cell lines, 60 surgically resected tumor tissues and their adjacent normal mucosas. Although the cripto mRNA was not detected in esophageal carcinomas or in normal mucosas, it was detected in gastric and colorectal carcinomas. In gastric carcinomas, 2.2 kb cripto mRNA was detected in one cell line, all the gastric carcinoma tissues and their adjacent normal mucosas. Of 23 gastric tumor tissues 8 (34.8%) exhibited a higher mRNA level than normal gastric mucosas. cripto mRNA was detected in 2 out of 6 colorectal carcinoma cell lines. Interestingly, 18 (81.8%) out of 22 colorectal carcinoma specimens expressed a higher level of cripto mRNA than that in normal mucosas. The level of the expression was higher than that in gastric carcinoma tissues. The expression was also correlated to tumor stage of colorectal carcinomas. PMID- 1938602 TI - A case-control study of stomach cancer and its genesis in relation to alcohol consumption, smoking, and familial cancer history. AB - A case-control study of stomach cancer and its genesis has been conducted in relation to alcohol consumption, cigarette smoking, and familial cancer history. Two hundred and ninety-four cancer cases, discovered by mass screening and histologically verified after endoscopic examination, have been compared with 588 randomly selected controls, who received the same early detection program and were verified as being free of the disease. No statistically significant association was observed between the development of stomach cancer and alcohol consumption or familial cancer history. However, the development of stomach cancer was found to have a positive correlation with smoking (relative risk for those who smoke less than 19 cigarettes/day, 3.56: 95% confidence interval, 2.39 to 5.31; relative risk for those who smoke more than 20 cigarettes/day, 2.58: 95% confidence interval, 1.60 to 4.17). The results of this study suggest that cigarette smoking appears to have a more harmful effect on the development of stomach cancer than either alcohol consumption or a familial history of cancer. The high relative risk of smoking revealed by this study implies that further research on the effects of smoking in the development of stomach cancer would be desirable. PMID- 1938603 TI - Local and systemic carcinogenic effects of alkylating carcinogens in rats treated by intravesicular administration. AB - Several nitrosamines and an azoxyalkane have been administered intravesically to groups of 12 female F344 rats, twice a week for 20 or 30 weeks. Many of the nitrosamines were as efficacious in giving rise to the same tumors of internal organs as when similar doses were administered orally, showing that absorption from the bladder was as rapid as from other sites. The tumors produced included lung and kidney tumors by nitrosodimethylamine, colon and Zymbal gland tumors by azoxymethane, liver tumors by methylnitrosoethylamine (but not by nitrosodimethylamine), liver and esophagus tumors by nitrosodiethylamine, liver and lung tumors by methylnitrosamino-3-pyridylbutanone, liver tumors by nitrosomorpholine, and tumors of the esophagus by methylnitroso-n-butylamine, 2,6 dimethyl-nitrosomorpholine and methylnitrosamino-N,N-dimethylethylamine. Bladder tumors were induced by intravesicular administration of only low doses of nitrosobis-(2-oxopropyl)amine and to a lesser extent by methylnitroso-n hexylamine and nitroso-(2-hydroxypropyl)(2-oxopropyl)amine, which all induced tumors systemically in addition. The bladder mucosa seemed to lack enzymes necessary to activate most nitrosamines to locally acting proximate carcinogens, but was quite transparent to the passage of carcinogenic nitrosamines present in the urine into the body to induce tumors in distant organs. PMID- 1938605 TI - Vision, interpretation, and the interactive field. AB - Interpretation is discussed relative to ways in which an analyst sees the material in question. Michael Fordham's approach to projective identification and 'defences of the self' is criticised and contrasted with one that orientates in 'third areas' between analyst and analysand. Through clinical material, these different approaches are discussed. The works of Jung and Bion are related, and Fordham's approach to interpretation is seen as originating from a vertex K, in particular his concept of childhood, in distinction to the vertex O which is the orientating position for processes in the third area. It is argued that in Fordham's approach O is saturated, that K does not evolve from O, and, furthermore, that his examples demonstrate that, contrary to what he says, in his activity he does not eschew memory, desire, and knowledge. PMID- 1938606 TI - Primordial image and the archetypal design of art. AB - This paper extends Jung's work on the relationship of art to (postulated) archetypes of the collective unconscious. Archetypes of the collective unconscious, according to Jung, are revealed to ego consciousness only by way of images--images of a specific form. Jung suggests that archetypes, primordial images, combine two aspects in a single form and are therefore paradoxical. The wise old man and youth and hermaphrodites illustrate Jung's definition of a primordial image. My study of Jung's illustrations concludes that he is referring to what I term double-figures as the design form of primordial imagery. I elaborate upon the design form of double-figures, and illustrate my conception of archetypal imagery through comparative analysis of nine cases of double-figure imagery from selected prehistoric and contemporary societies. Double-figures, as archetypal primordial imagery of the collective unconscious, are spontaneously generated, autonomous, and known to a wide variety of societies. I distinguish between form and content in the study of primordial imagery, and conclude with a summary of the importance of Jung to the cross-cultural study of art. PMID- 1938604 TI - Transforming activity of a synthetic c-Ha-ras gene containing O6-methylguanine in codon 12. AB - A mutagenic DNA-adduct, O6-methylguanine, was introduced into codon 12 of the synthetic c-Ha-ras gene by cassette mutagenesis. Transfection of this modified ras gene into normal NIH3T3 cells by the calcium phosphate procedure resulted in significant induction of focus formation. The ras gene inserted into the transformed cells was found to have a G to A transition at the position of the modified base. These results indicate that an O6-methylguanine residue in DNA may lead to a mutation and be one cause of activation of the ras gene. PMID- 1938607 TI - Conversion of bialaphos to other oligopeptides containing phosphinothricin by Streptomyces hygroscopicus. AB - Two oligopeptides containing phosphinothricin were accumulated in the culture of bialaphos (BA) producer Streptomyces hygroscopicus SF1293 when large amount of BA was added to the culture at idio phase. One of the oligopeptides was a new substance, BA dimer (phosphinothricyl-alanyl-alanyl-phosphinothricyl-alanyl-alan ine), and the other was a known substance called If (phosphinothricyl-alanyl alanyl-phosphinothricin). Though BA none producing mutants which were blocked at the steps 1, 10 and 13, respectively in BA biosynthesis also converted BA to BA dimer and If, the mutants blocked at the step 11 (alanylation) could not curry out the conversion. Antibiotic activities of BA dimer and If were lower than 1/100 of BA. PMID- 1938608 TI - Metabolic products of microorganisms, 260. Naphthgeranines, new naphthoquinone antibiotics from Streptomyces sp. PMID- 1938609 TI - Isolation of alpha-MAPI from fermentation broths during a screening program for HIV-1 protease inhibitors. PMID- 1938610 TI - Ribosomal binding and accumulation of rokitamycin in Bacteroides fragilis. PMID- 1938611 TI - Isolation and characterization of atramycin A and atramycin B, new isotetracenone type antitumor antibiotics. PMID- 1938612 TI - Cytoblastin, a low molecular weight immunomodulator produced by Streptoverticillium eurocidicum. PMID- 1938613 TI - Aureobasidins, new antifungal antibiotics. Taxonomy, fermentation, isolation, and properties. AB - Aureobasidins A to R were isolated from the fermentation broth of Aureobasidium pullulans R106. Aureobasidins are cyclic depsipeptide antibiotics with MW's ranging from 1.070 to 1,148. Aureobasidins showed high in vitro antifungal activity against Candida albicans. PMID- 1938614 TI - Structure of aureobasidin A. AB - Aureobasidin A, a new antifungal antibiotic, was isolated from the culture medium of Aureobasidium pullulans R106. Aureobasidin A was a cyclic depsipeptide consisting of eight alpha-amino acid units and one hydroxy acid unit. The structures of the units were found by acid hydrolysis of the antibiotic to be 2(R)-hydroxy-3(R)-methylpentanoic acid, beta-hydroxy-N-methyl-L-valine, N-methyl L-valine, L-proline, allo-L-isoleucine, N-methyl-L-phenylalanine, L-leucine, and L-phenyl-alanine. The sequence of the units was identified by NMR and FAB-MS of the products from the alkaline hydrolysis of aureobasidin A. PMID- 1938615 TI - Isolation of a bromo analog of rebeccamycin from Saccharothrix aerocolonigenes. AB - When grown in a defined medium containing 0.05% KBr, Saccharothrix aerocolonigenes ATCC 39243 produces a novel bromo analog of rebeccamycin. This new analog, designated bromorebeccamycin, has been isolated from the culture broth and purified by vacuum liquid chromatography and column chromatography. Spectroscopic data demonstrated that bromorebeccamycin has the same structure as rebeccamycin, except for the replacement of the two chlorine atoms by bromine atoms in the molecule. Bromorebeccamycin and rebeccamycin have a similar potency and activity against P388 leukemia in the murine model. PMID- 1938616 TI - Fluvirucins A1, A2, B1, B2, B3, B4 and B5, new antibiotics active against influenza A virus. IV. Taxonomy on the producing organisms. AB - The morphology, chemotaxonomy, and cultural and physiological characteristics were examined on the five strains of actinomycetes which produce antiviral antibiotics, fluvirucin congeners. All strains have meso-2,6-diaminopimelic acid in the cell wall. Four strains, Q464-31, L407-5, R359-5 and R516-16, belong to the maduromycetes since they have madurose in the whole cell. The remaining one strain, R869-90, has rhamnose but no madurose, and is a nocardioform actinomycete. These five strains were classified and designated as follows: Strain Q464-31 (fluvirucin A1 producer): Microtetraspora tyrrhenii sp. nov. (Actinomadura pusilla group). Strain L407-5 (fluvirucin B2 producer): A maduromycete. Strain R359-5 (fluvirucin B1 producer): Microtetraspora pusilla (Actinomadura pusilla group). Strain R869-90 (fluvirucin A2 producer): Saccharothrix mutabilis. Strain R516-16 (fluvirucins B2, B3, B4 and B5 producer): A maduromycete. PMID- 1938617 TI - Poststatin, a new inhibitor of prolyl endopeptidase, produced by Streptomyces viridochromogenes MH534-30F3. I. Taxonomy, production, isolation, physico chemical properties and biological activities. AB - Poststatin, a new inhibitor of prolyl endopeptidase (PEP) was discovered in the fermentation broth of Streptomyces viridochromogenes MH534-30F3. It was purified by Diaion HP-20, Sephadex LH-20 and YMC-gel (ODS-A) column chromatography and then isolated as a colorless powder. Poststatin has the molecular formula C26H47N5O7. The IC50 value of poststatin against the PEP of partially purified porcine kidney was 0.03 microgram/ml. It has low acute toxicity. No deaths occured after iv injection of 250 mg/kg of this agent to mice. PMID- 1938618 TI - Poststatin, a new inhibitor of prolyl endopeptidase, produced by Streptomyces viridochromogenes MH534-30F3. II. Structure determination and inhibitory activities. AB - Poststatin, a new inhibitor of prolyl endopeptidase, has been isolated from the culture broth of Streptomyces viridochromogenes MH534-30F3. The structure of poststatin was defined as L-valyl-L-valyl-3-amino-2-oxovaleryl-D-leucyl-L-valine by analysis of spectral properties and chemical studies of poststatin and its derivatives. The alpha-keto group of postine in poststatin plays the most important role on the inhibitory mechanism. PMID- 1938619 TI - New insecticidal metabolites from soil isolate W719. AB - In the course of screening soil organisms for new insecticidal metabolites, strain W719 was found to produce a group of metabolites active against the tobacco budworm Heliothis virescens. The active metabolites were purified by a combination of solvent partitioning and chromatographic steps, and the physico chemical properties and insecticidal activity of the main components were determined. The two main components have MW's of 925 and 939, appear to belong to the macrocyclic lactam family of natural products, and possess significant insecticidal activity. PMID- 1938621 TI - New N-alkyl derivatives of amphotericin B. Synthesis and biological properties. PMID- 1938620 TI - 6-(substituted methylene)penems, potent broad spectrum inhibitors of bacterial beta-lactamase. V. Chiral 1,2,3-triazolyl derivatives. AB - Structure-activity relationships in a series of (5R)-6-triazolylmethylene penems with potent beta-lactamase inhibitory activity are described. In most cases, their in vitro synergistic activity with amoxycillin is superior to that of clavulanic acid, sulbactam and tazobactam (YTR 830). Against an Escherichia coli TEM-1 infection in mice, the compounds showed a broad range of potencies; an optimum polarity was found, however, which gave maximum potency. PMID- 1938622 TI - Acclimatization resistance of a Pseudomonas aeruginosa prototype strain to imipenem. AB - A prototype sensitive strain of Pseudomonas aeruginosa (IRs) was acclimatized in vitro to imipenem by serial transfers in broth containing increasing concentrations of the antibiotic up to 32 micrograms/ml. Serial subculture of the resistant progeny (IR1r) in antibiotic-free solid media resulted in a "revertant" progeny (IR2r) that retained resistance to imipenem. Acclimatization resistance to imipenem and the attempted reversion procedure affected colony morphology, growth rate, pigment production, growth at 42 degrees C and glucose oxidation. SDS-PAGE analysis of the outer membrane proteins revealed in strain IR1r a complete loss of 6 proteins that were present in IRs (85 kdaltons, 46 kdaltons or porin D1, 45.5 kdaltons or porin D2, 43 kdaltons or porin E, 21 kdaltons or protein H1 and 20.5 kdaltons or lipoprotein H2) and in strain IR2r a complete loss of 3 proteins (46 kdaltons, 43 kdaltons, 20.5 kdaltons), while three others were found only in trace amounts (75 kdaltons, 45.5 kdaltons and 21 kdaltons). In the outer membranes of strains IR1r and IR2r an acquisition of a 56-kdalton protein was noted. Lipopolysaccharide chemical analysis revealed a marked, partially reversible increase in 2-keto-3-deoxyoctonate, total hexose and heptose constituents; readily extractable lipid chemical analysis and TLC, revealed a marked, partially reversible, increase in the phospholipid content of the outer membrane. Acclimatization resistance to imipenem was accompanied by cross resistance to gentamicin, by partially reversible cross-resistance to moxalactam, carbenicillin and ticarcillin and by fully reversible cross-resistance to aztreonam. Sensitivity to azlocillin and polymyxin B remained unaltered. To explain this type of resistance to imipenem, an irreversible, non-inducible "loss" mutation mechanism, working in concert with a partially reversible mechanism, is proposed. PMID- 1938624 TI - The development of links between stereocilia in hair cells of the chick basilar papilla. AB - Auditory papillae of chicks (embryonic age 6-21 days) were examined by scanning and transmission electron microscopy, in order to trace the development of the tip links between the stereocilia, and in order to trace the development of the spatial organisation of the tip links. In the most immature bundles, stereocilia were not graded in height, while strands of tenuous material interconnected adjacent stereocilia, this material being concentrated in a band near the tips of the stereocilia. The material joined the stereocilia in all directions, with no preferential direction for the interconnecting material being visible. Similarly, no columnar organisation of the stereocilia was visible. As soon as a gradation in height of the stereocilia began to appear, material could be seen running upwards from the shorter stereocilia to the adjacent lengthening stereocilia. There was a continuum in appearance between (i) the material running laterally between short immature stereocilia, (ii) the material running upwards between stereocilia which were developing a gradation in height, and (iii) the tip links seen in more mature bundles. It is suggested that tip links are a specialisation of the links which join immature stereocilia laterally near their tips. It is also suggested that the orientation of tip links, parallel to the hair cell axis of bilateral symmetry, is produced by the gradient in growth of the stereocilia. PMID- 1938623 TI - Cloning of large DNA fragments, which hybridize with actinorhodin biosynthesis genes, from kalafungin and nanaomycin A methyl ester producers and identification of genes for kalafungin biosynthesis of the kalafungin producer. AB - Large actI, III-homologous DNA fragments were isolated from genomic libraries of the strains that produce the benzoisochromanequinone antibiotics kalafungin and nanaomycin A methyl ester, Streptomyces tanashiensis strain Kala and Streptomyces sp. OM-173, respectively. These libraries were prepared in Escherichia coli JM108 by using a novel Streptomyces-E. coli bifunctional cosmid, pKU205, and screened with polyketide synthase genes (actI and III) for actinorhodin biosynthesis from Streptomyces coelicolor A3(2) as probes. The cloned DNA fragments (28 and 42 kb) were analyzed by hybridization with DNA containing actinorhodin biosynthetic genes (actI, II, III, IV, VA, VB, VI and VII). Both fragments hybridized with the actI, III, VA and VI regions, but not with the actII, IV, VB and VII regions. The cloned fragment of S. tanashiensis DNA was analyzed by complementation tests with kalafungin-nonproducing mutants. Seven genes (kalI approximately VII), which correspond to seven steps in kalafungin biosynthesis, were found to be located on a 14 kb continuous DNA fragment. Five of the genes were located on the regions homologous to the genes for actinorhodin biosynthesis, but the other two genes were not. Although kalafungin is an intermediate or shunt product in actinorhodin biosynthesis in S. coelicolor A3(2), the genes for kalafungin biosynthesis in S. tanashiensis are not identical with those in S. coelicolor A3(2). PMID- 1938625 TI - Critical bandwidth and consonance in relation to cochlear frequency-position coordinates. AB - A recent paper (Greenwood, 1990) has reviewed some of the data in the literature on the frequency-position coordinates of the cochlear partition in a number of species and the degree to which they are fitted by empirical functions developed in 1961 (Greenwood, 1961b, 1974b). Continued confirmation by physiological data makes this frequency-position function more independent of non-physiological data and provides a more secure means of testing possible relations of psychoacoustic data to cochlear coordinates. The present paper reviews various sets of critical band, or similar, data in humans and other species and finds that a considerable body of bandwidth estimates correspond to equal distances along the cochlear partition (on this assumption), confirming also to an exponential function of distance. As shown in 1961, such a function would imply that the same set of bandwidths is also a linear function of frequency. Some of the early critical bandwidth, and also 'consonant interval', estimates in man correspond to equal distances on the cochlear partition to a degree not generally recognized. Thus above about 300 to 500 Hz most of the critical band data (of Zwicker and Gassler collated by Zwicker et al., 1957), correspond quite well to equal distances on the Bekesy-Skarstein cochlear map fitted by the frequency-position function, as opposed to the values published in the critical band table or curve (which do not do so above 3 kHz). Consonant interval data tend to correspond closely to equal distances, from below 100 Hz to about 3 kHz. Certain post-1961 'critical band' (ERB) estimates collated by Moore and Glasberg (1983) and extended by Moore et al. (1990) and Shailer et al. (1990) also correspond quite closely to constant distances calculated by the 1961 function. So too do some, but not all, of the frequency intervals shown by Plomp (1964) and Plomp and Mimpen (1968) to be required to resolve the components of a harmonic complex. Some critical bandwidth data from animal studies may also correspond approximately to equal distances. This survey of old and new results, plotted on a rational distance scale, may assist in explaining what potential mix of factors operates to determine the estimated bandwidths when the values differ across experiments or in different frequency ranges. The correspondence, in the preponderance of cases, of critical bandwidth to a constant distance may facilitate an understanding of the operational definitions of critical bandwidth in different experiments and of the common underlying mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1938626 TI - Critical bandwidth and consonance: their operational definitions in relation to cochlear nonlinearity and combination tones. AB - A recent paper (Greenwood, 1990) reviewed cochlear coordinates in several species in relation to empirical frequency-position functions (Greenwood, 1961b, 1974b), one of which well fits the Bekesy-Skarstein human cochlear map (Bekesy, 1960; Kringlebotn et al, 1979). This increased the independence of the human function from the psychoacoustic data originally used to construct it and encouraged a second assessment of the relations of similar psychoacoustically significant bandwidths to distance and position on the cochlear map. The companion paper (Greenwood, 1991, this issue), found that, among such bandwidths, 'classical' critical bandwidth, and also 'constant interval', estimates in man correspond to equal distances to a closer extent than generally recognized, and over large parts of the frequency range they conform also to an exponential function of distance, as do most of the ERB estimates. This correspondence to almost constant and similar distances facilitates, and forms a part of, an explanation of the operational definitions of critical bandwidth in different experiments. The present account recapitulates the basic explanation of critical bandwidth and consonance offered in Greenwood (1971, 1972b, 1973b, 1974b) and Greenwood et al. (1976): by adding schematic details to the earlier account of critical bandwidth measurements in pure tone masking (the masker-notch interval), two-tone masking, narrow-band masking, and two-tone dissonance-consonance judgements and by outlining its applicability to AM and Quasi-FM detection and to two-band (nominally notched-noise) masking experiments. The measured bandwidths derive from approximately uniform dimensions of traveling wave envelopes in the peak region and from the effects of the resulting spatial pattern of nonlinear interference among primary components. In this account, critical bandwidth in man corresponds to a distance of about 1 or 1.25 mm, depending upon the direction the interval projects from the stimulus frequency to which it is referenced. It is identified with the apical segment of the traveling wave displacement envelope, which in guinea pig and squirrel monkey appears to be about 2/3rds and 3/4ths of a millimeter, respectively and would be about 1.25 mm in man if these distances were scaled (Greenwood, 1962) among these three species (Greenwood, 1974b, 1977a). When reflected also in the basal direction, the upper end of the frequency interval, at a 1.065 mm distance, makes a total two-critical-band distance, which corresponds with the region of nonlinear input-output functions that extends in both directions from the envelope peak and hence also with the frequency-dispersive region of accelerated phase accumulation (Greenwood, 1974b, 1977a).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1938627 TI - Anaesthetics may change the shape of isolated type I hair cells. AB - Type I hair cells isolated from animals anaesthetised with barbiturates or ether were found to be shorter and to lack a prominent 'neck' region when compared to cells isolated from non-anaesthetised animals. Ketamine did not have this effect. The changes observed could have important implications for the physiology of inner ear receptors. These findings infer that care should be taken in the choice of anaesthetics used in studies on cells from the inner ear. PMID- 1938629 TI - Effects of neonatal deafening and chronic intracochlear electrical stimulation on the cochlear nucleus in cats. AB - Four newborn kittens were deafened by daily intramuscular injections of neomycin sulfate, beginning the day after birth and continuing for 14-16 days. At 10-16 weeks of age the deaf kittens were implanted unilaterally with a four wire intracochlear electrode array. The animals were stimulated daily (starting at 13 18 weeks of age), for a period of one hour, at 6 dB above the electrically evoked auditory brainstem response threshold. After 3 months of chronic intracochlear electrical stimulation, animals were studied in acute electrophysiological experiments and euthanized for histological studies. This study compares the stimulated and control cochlear nuclei (CN) of these deafened animals to the CN of four normal adult cats. Statistical comparisons of spherical cell densities in the anteroventral cochlear nucleus (AVCN), cross-sectional spherical cell areas, and volumes of the cochlear nucleus subdivisions were included in the analysis. The results indicate that, by all of these measures, the cochlear nuclei in neonatally deafened animals were significantly different from the cochlear nuclei of control animals. As a result of deafening, the density of spherical cells was decreased by 30%, the cross-sectional areas of spherical cells were reduced by 20%, and the volume of the cochlear nucleus was reduced by 25%. These changes were observed in both cochlear nuclei (ipsilateral to both stimulated and unstimulated ears) of the deafened animals. With the measures employed, no significant difference was demonstrated in comparisons between the deafened/unstimulated and the deafened/stimulated cochlear nuclei. That is, no reversal of the profound effects of deafening was observed in the cochlear nuclei as a consequence of chronic intracochlear electrical stimulation which was begun 11 to 16 weeks after deafening. PMID- 1938628 TI - Chronic intracochlear electrical stimulation induces selective survival of spiral ganglion neurons in neonatally deafened cats. AB - Ten newborn kittens were deafened by systemic administration of neomycin sulfate. Profound hearing losses were documented by ABR and FFR (500 Hz) testing. At 9-17 weeks of age, the young deafened cats were unilaterally implanted with a multichannel scala tympani electrode. Six of the animals were chronically stimulated at 6 dB above electrically evoked ABR thresholds for 1 h/day for periods of 1 month or 3 months. Stimuli were charge-balanced biphasic pulses (200 microseconds/phase, 30 pps.) The remaining 4 cats underwent identical deafening and implantation schedules but were not stimulated. Results indicate that administration of neomycin in neonatal cats induced degeneration of hair cells and spiral ganglion cell loss that was bilaterally symmetrical between the two cochleas of each individual animal, although there was variation between animals in the severity of the ototoxic drug effect. In animals receiving passive (unstimulated) implants, morphometric analysis of spiral ganglion cell density showed no significant difference in ganglion cell survival between the implanted cochleas and the contralateral control ears. In contrast, animals that were chronically stimulated for 3 months showed significantly better neuronal survival in implanted and stimulated cochleas as compared to contralateral deafened control ears. The induced conservation of spiral ganglion neurons was observed consistently within the basal cochlear region near the stimulating electrodes. In more apical regions there was no significant difference between the stimulated and control cochleas. The mechanisms underlying this selective conservation of spiral ganglion neurons induced by chronic intracochlear electrical stimulation are uncertain. Since no comparable chronic stimulation studies have been conducted in adults, it is not known whether similar conservation effects could be induced in mature animals. PMID- 1938630 TI - Changes in the stereocilia and non-monotonic pattern of threshold shift after exposure to impulse noise. AB - The recovery pattern of threshold shift (TS) and 'dynamic' changes in the stereocilia after exposure to high-level impulse noise in guinea pigs were investigated. 33 albino guinea pigs were exposed to 10 impulse noises at the rate of 1/min. The noise had peak level of 166 dB SPL and a duration of 0.1 ms. Thirteen of the exposed animals were used to systematically measure threshold shifts at regular intervals from 0.5 h to 30 days post-exposure by click auditory cortex evoked response (AC-ER). Twelve of the animals who had typical TS at the same intervals were killed for scanning electron microscopic examination. The recovery pattern of threshold shifts was non-monotonic, which was different from that seen with continuous noise. There was an increase in TS after the exposure and the maximum level of TS was found at 8 h post-exposure. Morphological analysis also showed delayed changes in the stereocilia after exposure. The severity of changes in the stereocilia reached a peak at 8 h, at which time complete fusion of hair bundles took place. The tectorial material found on the tips of the stereocilia may be responsible for the sequence of the changes. PMID- 1938631 TI - Malleus vibration mode changes with frequency. AB - The mode of vibration of the cat manubrium is investigated by measuring its vibration in response to sound stimulus at four locations between the umbo and the processus lateralis with a heterodyne interferometer. The determination of mode requires high precision in measurement because amplitude differences between the points are small (about 20% at low audio-frequencies). Changes in the frequency response with time have been reported in an earlier paper. The nature and magnitude of this time change is analysed in detail: over a period of 1 h the average change in amplitude is about 5% and in phase 5 degrees. The malleus vibration at some frequencies is purely translational, it is rotational at others and mixed at most frequencies. When the motion is rotational the position of the axis of rotation shifts with frequency, the shifts are so large that the axis can lie near the umbo so that amplitudes at the processus lateralis are larger than at the umbo. The classical concept of the malleus rotating around a fixed axis running from the anterior mallar to the posterior incudal ligament fits our measurements only at low frequencies. PMID- 1938632 TI - Effects of breeding season length and calving season on range beef cow productivity. AB - A 5-yr study was conducted beginning in 1983 with 460 cows to evaluate the effects of three breeding seasons (30, 45, and 70 d in length) and two times of spring calving, March (early) and April (late), on cattle production under Nebraska Sandhills range conditions. Criteria evaluated included pregnancy and weaning percentages, calving date and distribution, cow weights and body condition at four intervals, calf birth and weaning weights, and cow productivity. The 30-d breeding season included a 10-d estrus synchronization and AI period; in the other breeding seasons only natural breeding was used. The same sires were used over the entire study period. Percentage of cows pregnant and percentage of calves weaned were lower (P less than .01) for cows bred for 30 d than for cows bred for 45 or 70 d. Average calving dates were similar among the breeding groups within the early and late calving herds. Pregnancy rates from AI were higher (P less than .01) for the cows calving in April (64%) than for the cows calving in March (41%). Cows calving in April lost less weight between precalving and prebreeding and were heavier (P less than .05) at prebreeding time than the cows calving in March. Calf weaning weights were not different (P greater than .10) among any of the breeding season groups or between the two calving herds when calves were weaned at a similar age. Cow productivity (calf weaning weight per breeding female) was highest (P less than .05) for the cows bred for 70 d (186 kg), intermediate for the cows bred for 45 d (172 kg), and lowest for cows bred for 30 d (162 kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938633 TI - Lifetime production of beef heifers calving first at two vs three years of age. AB - Records of Angus, Hereford, Shorthorn, and first-cross cows born from 1960 to 1963 were used to study the effect of age at first calving and culling policy on cumulative survival (SU), number of breeding seasons (BS), pregnancies (PG), calves born (CB) and alive at 72 h (C72) and at weaning (CW), calf weaning weights (WW), and input/output efficiency, up to 12 yr of age. The 155 cows born in 1960 and 1961 calved first at 3 yr of age (M3) and the 173 born in 1962 and 1963 calved at 2 yr of age (M2). Analyses included both actual culling of cows open in two consecutive years (AC) and imposed culling of any open cow (IC). Also, economic efficiency for no culling (NC) of cows for infertility after first calving and up to 10 yr of age was calculated. The model included cow birth year sire breed of cow (Y-S), sires within Y-S, breed of cow's dam (D), and D x Y-S. Linear functions of Y-S were used to estimate means for M2 and M3 cows. Under AC, by 12 yr of age M2 exceeded M3 cows by 6.8% SU, 1.1 BS, 1.2 PG, 1.1 CB, 1.0 C72, .9 CW, and 138 kg WW (P less than .10). Under IC, M2 exceeded M3 cows by only .7% SU, .3 BS, .3 PG, .3 CB, .2 C72, and .1 CW; and M3 produced 24 kg more WW than M2 cows (P greater than .10). Economic efficiency was higher for M2 than for M3 cows (greater than 10% at 6 yr to greater than 5% at 12 yr culling age), regardless of culling policy. Economic efficiency was maximum when terminal age of cows was 6 to 9 yr for M2 and 8 to 9 yr for M3 cows. Repeatability of pregnancy was higher (P less than .05) for M3 (19%) than for M2 (2%) cows. Economic efficiency for M2 or M3 cows under NC was slightly poorer (2 to 3%) than under either AC or IC policies. Economic efficiency can be improved by managing heifers to calve first as 2-yr-olds under either mild or intense culling of open cows. PMID- 1938634 TI - Type and mixtures of high-moisture corn in beef cattle finishing diets. AB - In three experiments consisting of three finishing trials each, five corn storage and(or) feeding treatments were evaluated: 1) dry whole (DWC); 2) whole high moisture (WHMC); 3) mixture (MHMC) of ground (GHMC) or rolled (RHMC) high moisture corn with WHMC; 4) GHMC stored in a bunker silo; and 5) RHMC, corn stored whole but fed in rolled form. In Exp. 1, gains and feed intakes of steers fed whole corn (DWC vs WHMC) were similar. Steers fed GHMC and RHMC had lower (P less than .05) gains and intakes than steers fed whole corn. However, feed to gain ratios were 9% better (P less than .10) for steers fed RHMC than for steers fed GHMC. In Exp. 1 and 2, gains of steers fed MHMC were intermediate to gains of steers fed whole (DWC and WHMC) or processed corn (GHMC and RHMC). Feed to gain ratios of steers fed whole or processed corn were similar to feed to gain ratios of steers fed MHMC. In Exp. 3, steers fed 28.6% moisture GHMC had lower (P less than .05) intakes and feed to gain ratios than steers fed 22.5% moisture GHMC. Intakes and feed to gain ratios decreased 1.2 and 1.4%, respectively, for each 1% increase in corn moisture. Data are interpreted to mean that the relative effect of corn moisture content on cattle performance depends on form of corn fed; positive associative effects of MHMC are negligible, but RHMC has a greater feed value than GHMC. PMID- 1938635 TI - Traits affecting postweaning weight gain and feed intake of primiparous sows. AB - Seventy-six primiparous Duroc and Landrace sows from two genetic lines with or without selection for improved sow productivity were used to identify sow traits that affect postweaning gain (positive or negative) and feed intake. Sows lost weight (P less than .01) and consumed less feed (P less than .01) during wk 1 postweaning (37 d) compared with wk 2, 3, and 4. Sows gained more weight during wk 2 and 3 (P less than .01) than during wk 4. Weekly feed consumption was similar during wk 2 and 4 and highest during wk 3 (P less than .05). Sow weight gain postweaning was predicted by sow weaning weight (P less than .01) and adjusted 21-d litter weight (P less than .05) during wk 1, wk 1 to 2, and wk 1 to 4 feeding periods. Feed consumption was best predicted by adjusted litter weaning weight (P less than .01), sow weaning weight (P less than .01), average backfat at farrowing (P less than .01), average backfat change (P less than .05), and adjusted 21-d litter weight (P less than .05). Feed intake was positively correlated (P less than .01; r = .77) and sow weight at breeding, farrowing, and weaning was negatively correlated (P less than .05; r = -.23, -.21, and -.26, respectively) with sow weight gain. Average backfat at weaning was negatively correlated (P less than .05) with gain and feed intake during each period. Adjusted 21-d litter weight and adjusted litter weaning weight were positively correlated with postweaning feed intake (P less than .05; r = .22 and .23, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938636 TI - Comparison of rabbit breed types for postweaning litter growth, feed efficiency, and survival performance traits. AB - Postweaning data on 643 rabbits from 122 litters representing four breed types, New Zealand White (NZW) and Californian (CAL) purebreds, CAL X NZW (CXN), and Flemish Giant (FG) crossbreds (the latter group was a collection of FG X CAL, FG X Champagne D'Argent [CHA], and 1/2 FG X 1/4 CAL X 1/4 CHA), were gathered over five seasons and compared for growth, feed efficiency, and survival-related performance traits. Evaluation criteria included litter size and weight at weaning (28 d); 28- to 70-d litter feed intake, weight gain, feed efficiency, and mortality rate; and litter and average market weight (70 d). The least squares model included main effects of breed type, season of birth of the litter and parity of dam, litter size at weaning as a linear covariate, and the random error. Breed-type differences were not detected for litter size and weight at weaning and feed efficiency. Purebred NZW and CAL litter trait performances were comparable (P greater than .05). Purebred NZW litters consumed less feed than CXN and FG crosses, gained weight less rapidly than FG crosses, and weighed less per fryer at 70 d than CXN and FG crosses (P less than .05). Feed intake was lower and average market weight was lighter for CAL purebred litters than for CXN and FG crossbred litters (P less than .05). The CXN and FG crossbreds only differed (P less than .05) for average market weight (2,078 vs 2,192 g). Mortality rate was lower (P less than .05) in CXN crossbred litters than in CAL purebred litters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938637 TI - Pig weaning weight and changes in hematology and blood chemistry of sows injected with recombinant porcine somatotropin during lactation. AB - Weaning weight of pigs on d 18 to 21 of age was used to determine the effects of recombinant porcine somatotropin (rpST) on lactational performance of their dams. Crossbred Landrace x Yorkshire sows (n = 180, 202 to 270 kg BW) were assigned to receive daily i.m. injections of either 0, 8, or 16 mg of rpST on lactation d 7 to 20. Initially, injections of 16 mg of rpST/d caused 100% mortality (four sows); thus, a dose of 4 mg of rpST/d replaced 16 mg. Subsequently, 5 of 19 and 1 of 17 sows died in response to daily injections of 8 and 4 mg of rpST, respectively, resulting in termination of the experiment. Before termination, 48 sows (16 from each of the 0-, 4-, and 8-mg treatment groups) completed a lactation of 18 to 21 d in duration. Analysis of these data indicated that daily injection of lactating sows with rpST increased (P less than .05) weaning weight of pigs only if they were from litters that averaged greater than or equal to 2.6 kg/pig on lactation d 7. The BW of sows was decreased by rpST (P = .07). Subsequent experiments revealed 1) that rpST-induced death of lactating sows was caused from hemorrhaging of ulcers that developed at the pars esophagea, 2) that there was vacuolation of the liver and kidney of dead sows, and 3) that daily injection of 16 mg of rpST into nonlactating growing pigs (50 to 100 kg BW) for 28 d did not cause death or any observable illness in spite of 100% mortality of lactating sows after two to nine injections. PMID- 1938639 TI - Effects of ewe breed and management system on efficiency of lamb production: III. Meat characteristics. AB - Effects of management system, ewe breed, sex, and legume grazing on cooking and sensory characteristics and shear force of lamb meat were estimated from data collected on animals produced in three management systems. System 1 lambs were born in late fall and fed to slaughter on a concentrate diet. System 2 lambs were born in January and February and grazed pure stands of alfalfa or ladino clover after weaning. System 3 lambs were born in March and April and remained with their dams on native bluegrass-white clover pasture throughout the grazing season. Lambs were progeny of either 1/2-Suffolk, 1/2-Rambouillet ewes or 1/2 Suffolk, 1/4-Finnsheep, 1/4-Rambouillet or Dorset ewes and were sired by Suffolk rams. Lambs were slaughtered at 50 (females) to 55 kg (males). One-half of the males in System 1 were left intact; all males in Systems 2 and 3 were castrated. Mean age at slaughter was 156, 204, and 234 d for lambs in Systems 1, 2, and 3, respectively. Cooked weight of loin chops averaged 68.5% of uncooked weight and did not differ among systems. Shear force was greatest for System 1 lambs and least for System 3 lambs in yr 1, but systems did not differ in shear performance in yr 2. System differences in tenderness favored System 3 lambs. Although mean flavor intensity was least for System 2 lambs, the frequency of high-intensity, potentially objectionable flavors was highest for these lambs and especially for those grazing alfalfa. In general, however, sensory characteristics did not differ greatly among production systems, and correlation analysis revealed little potential to use carcass traits to predict meat characteristics. PMID- 1938638 TI - Effects of exogenous porcine somatotropin (pST) administration on growth performance, carcass traits, and pork meat quality of Meishan, Pietrain, and crossbred gilts. AB - Seventeen to twenty-three females of lean (Pietrain, PI), fat (Meishan, MS), or intermediate genotype (PI x [3/4 Large White x 1/4 MS]), referred to as crossbred (CR), were injected between 60 and 100 kg live weight with 6 mg/d of porcine somatotropin (pST) and compared to similar numbers of control females receiving the vehicle only. Average daily gain increased similarly in the three genotypes (125 g/d). Feed conversion ratio tended to decrease to a higher extent in MS ( 2.0 kg of feed/kg of gain) than in the other two genotypes (-1.1 and -.9 kg of feed/kg of gain for CR and PI, respectively). A significant genotype x treatment interaction was also observed for backfat thickness (BF) and fat, muscle, and bone development. Effects of pST in PI, CR, and MS pigs were, respectively, -6.2, -9.6, and -16.1 mm for BF and 3.0, 6.8, and 11.8% carcass muscle. The influence of pST on physical measurements of meat quality was rather low, although desirable effects (P less than .05) were obtained on the reflectance and water holding capacity of PI and CR. Intramuscular fat content was reduced by approximately 1% in MS and CR but not in PI. The metatarsals of pST-treated animals had a higher water content (except in PI), a lower mineralization, and a lower breaking strength (except in MS). The existence of breed variations in the response to pST might result in changes of the relative merit of crossbreeding schemes. PMID- 1938640 TI - Estimates of covariances between reproduction and growth in Australian beef cattle. AB - Estimates of covariance components between scrotal circumference, serving capacity, days to calving, and yearling and final weight were obtained for Hereford, Angus, and Zebu cross cattle in temperate and tropical Australia. Analyses were carried out by REML employing a derivative-free algorithm and fitting bivariate animal models. Aspects of modeling and computational requirements related to the use of this method are discussed. Estimates of heritabilities agreed closely with those from univariate analyses, being low for female reproductive performance and moderate to high for male reproduction and growth. Estimates of genetic correlation between male and female fertility traits were low but favorable, being -.25, -.28, and -.41 between scrotal circumference and days to calving for Herefords, Angus, and Zebu crosses, respectively. Genetic correlations between male reproductive traits and weights ranged from .24 to .52 for the temperate breeds and were higher (.65 to .69) for Zebu crosses. Phenotypic correlations between scrotal circumference and weights were similar for all breeds, ranging from .32 to .47, whereas serving capacity and weights were phenotypically unrelated. Estimates of correlations between days to calving and weights were less consistent. Phenotypically, there was little association between the two traits. Genetic correlations for Zebu crosses were negative and low to moderate (-.36 to -.66) and estimates for Angus were close to zero. PMID- 1938641 TI - Life-cycle biological efficiency of Bos indicus x Bos taurus and Bos taurus crossbred cow-calf production to weaning. AB - A deterministic model was developed that accounted for all biological inputs and outputs for a theoretical herd of F1 females at age equilibrium mated to produce three-way terminal-cross calves and for the required proportion of straightbred cows needed to produce replacements. Two Bos indicus x Bos taurus vs two Bos taurus x Bos taurus types of crossbred cows were compared in the production environment of south-central Nebraska. The four types of F1 females were from Hereford (H) or Angus (A) dams and by H or A (HA), Pinzgauer (Pz), Brahman (Bm), or Sahiwal (Sw) sires. The crossbred females were assumed mated to Red Poll (R) sires for their first calving and to Simmental (S) sires thereafter. Two evaluations of efficiency for each of the four breeding systems were total cow and calf feed energy input 1) per unit of only weaned calf weight output (CALFEFF, Mcal/kg) and 2) per unit of weaned calf plus .55 x cull cow weight output (TVALEFF, Mcal/kg). Results for a terminal age of 7 yr in systems using HA, Pz, Bm, and Sw crossbred cows, respectively, were 64.9, 64.5, 60.9, and 59.3 Mcal/kg for CALFEFF and 45.7, 46.4, 44.1, and 43.7 Mcal/kg for TVALEFF. Changing terminal age to 11 yr reduced CALFEFF about 6% but increased TVALEFF about 7%, because total inputs increased more than output value (10 vs 3%) from 7 to 11 yr terminal ages. These results suggest differences in efficiency among these breed crosses favoring the Bos indicus crossbred cows by over 4% in this particular environment. PMID- 1938642 TI - A performance programmed method for computing inbreeding coefficients from large data sets for use in mixed-model analyses. AB - Coefficients of inbreeding are commonly used in mixed-model methods for forming inverses of Wright's numerator relationship matrix and transformation matrices used in variance component estimation and national cattle evaluation. Computation of exact coefficients of inbreeding from very large data sets has been believed to be too expensive or too difficult a task to perform. Approximate methods have been used instead. The effects of using approximation methods for inbred data that appear in national cattle data sets are demonstrated. An algorithm is given for the computation of inbreeding coefficients for large data sets. The algorithm feasibly computes inbreeding coefficients for large data sets even on small computing architectures. PMID- 1938643 TI - Breed effects and heterosis in advanced generations of composite populations for birth weight, birth date, dystocia, and survival as traits of dam in beef cattle. AB - Heterosis effects were evaluated as traits of the dam in F2 progeny of F1 dams and F3 and 4 progeny of F2 and 3 dams in three composite populations of beef cattle. Traits included birth weight, birth date, calving difficulty percentage, and survival percentage at birth, 72 h, and weaning for calves with dams of different age classes. Breed effects were evaluated for the nine parental breeds (Red Poll [R], Hereford [H], Angus [A], Limousin [L], Braunvieh [B], Pinzgauer [P], Gelbvieh [G], Simmental [S], and Charolais [C]) that contributed to the three composite populations (MARC I = 1/4 C, 1/4 B, 1/4 L, 1/4 H, 1/8 A; MARC II = 1/4 G, 1/4 S, 1/4 H, 1/4 A; and MARC III = 1/4 R, 1/4 P, 1/4 H, 1/4 A). Among calves with 2-yr-old dams, breed effects were significant for birth weight, birth date, calving difficulty percentage, and survival percentage at birth but not at 72 h and weaning. Calf survival at weaning was lowest for smallest (less than mu 1.5 sigma) and largest (greater than mu + 1.5 sigma) birth weight classes and did not differ among intermediate birth weight classes. Calves with difficult births with 2-yr-old dams were significantly heavier at birth (39.6 vs 35.4 kg) and had significantly lower survival at 72 h (87.1 vs 92.2%) and at weaning (77.4 vs 85.1%) than calves with 2-yr-old dams that did not experience difficult births. Among calves with dams greater than or equal to 3 yr old and from dams of all ages, breed group effects generally were significant for the traits analyzed. Important breed group effects on dystocia and survival traits were observed independent of breed group effects on birth weight. Effects of heterosis were significant for birth weight for each generation of each composite population and for the mean of the three composite populations. Generally, heterosis effects for calving difficulty percentage were not significant. Effects of heterosis generally were significant for date of birth (earlier) for each composite population and for the mean of the three composite populations. Heterosis effects on survival to weaning percentage generally were positive but generally were not significant. Heterosis retained for birth weight, birth date, and survival percentage in combined F3 and 4 generation progeny of combined F2 and 3 generation dams did not differ (P greater than .05) from expectation based on retained heterozygosity. These results support the hypothesis that heterosis in cattle for these traits is the result of dominance effects of genes. PMID- 1938644 TI - Ovulation rate and pre- and postimplantation survival in mice with a major gene for rapid postweaning gain. AB - Differences in ovulation rate, embryo survival, litter size, and fertility are presented for four lines of mice that have been selected for growth or are homozygous for a recessive gene (hg) imparting rapid postweaning gain. Two of the lines were hg/hg, one in a growth-neutral and one in a growth-selected background. The remaining two were Hg/Hg (the corresponding normal, dominant allele with no effect on postweaning gain) in the same two backgrounds. Average ovulation rates ranged from 10.9 to 17.1 eggs shed, and litter sizes ranged from 8.6 to 14.0. In the growth-selected background, the hg allele reduced the number of ovulations, implantation, and litter size by nearly three compared with the Hg/Hg controls. The impact of the hg allele in the growth-neutral background was not significant. When males of a different line selected for high litter size were mated to females of the four stocks, more than two additional eggs, implants, and pups were recorded, compared with results of mating to males of the same line as the female. PMID- 1938645 TI - Technical note: isolation and characterization of sheep ruminal epithelial cells. AB - A system for the isolation and characterization of sheep ruminal epithelial cells has been developed. Ruminal papillae from the ventral cranial sac of 12- to 24-wk old Dorset ram lambs were subjected to serial tryptic digestions. Initial digestions (two 15-min periods) in the series were used to remove keratinized cells of the stratum corneum, which were able to produce only small amounts of beta-hydroxybutyrate from butyrate (5.37 +/- .72 nmol/120 min/per milligram of dry cell weight). Later digest fractions, containing primarily cells from the stratum basale, exhibited high viabilities (75 to 95%) and proved capable of converting butyrate to beta-hydroxybutyrate at relatively high rates (33.6 +/- 6.7 nmol/120 min per milligram of dry cell weight). Neither acetate nor propionate underwent significant conversion to beta-hydroxybutyrate. However, addition of acetate inhibited (77.4% of control) and addition of propionate stimulated (200% of control) beta-hydroxybutyrate production. Acetate addition reduced the propionate-induced stimulation of beta-hydroxybutyrate production from butyrate (136% of control). These results are similar to those obtained from in vitro incubations of ruminal papillae and suggest that an isolated cell system may prove useful in the further study of ruminal epithelial metabolism. PMID- 1938646 TI - Nutritional, physiological, genetic, sex, and age effects on fat-free dry matter composition of the body in avian, fish, and mammalian species: a review. AB - The purpose of this review is to outline and interpret the effects of nutrition, physiological state, sex, genetics, and age on composition of the fat-free dry matter of birds, mammals, and fishes in order to test the hypothesis that the protein:ash ratio in the body is constant. Calculations from a broad array of published data revealed that nutritional factors, including mineral, protein and amino acid nutriture, frequency and level of feeding, and energy intake and nonnutritional factors, including physiological state, sex, genetic background, and age of animal, may each alter the ratio of protein:ash in the body. All or part of the response may be associated with changes in accretion of body protein and(or) skeletal development and mineralization imposed by these nutritional and nonnutritional factors. In most cases of amino acid or protein deficiency, the protein:ash ratio was decreased relative to the control because the deposition of protein in muscle and viscera was reduced more than the growth and mineralization of the skeleton. In other cases, the protein:ash ratio was increased relative to a control because the dietary Ca or P intake or absorption limited skeletal mineralization. More knowledge is needed of how skeletal development and protein:ash ratio in the body is regulated, especially under the influence of nutritional, ontogenetic, and physiological variables among different genotypes of mammals, birds, and fishes. Documentation that the protein:ash ratio in the whole body of representative mammals, birds, and fishes is not constant, but is subject to manipulation, has important physiological and economic implications for developing food animals for the efficient production of lean meat. PMID- 1938647 TI - Fatty acid metabolism by the porcine placenta. AB - Two experiments were performed to determine whether esterification is a major pathway of fatty acid utilization within porcine placenta and to determine what metabolic parameters may limit fatty acid transfer to the fetal pig. Maternal (endometrium) and fetal (chorioallantois) placenta were obtained by Caesarean section at d 110 of gestation in both experiments. Eight gilts were used in the first experiment. Tissue sections were incubated with palmitate at concentrations ranging from .25 to 2.0 mM. Maternal placenta metabolized palmitate at a higher rate than fetal placenta, although fetal placenta was more efficient in esterifying palmitate. Esterification composed the majority of palmitate utilization within fetal and maternal placenta. The second experiment evaluated the effect of dietary lipid on placental fatty acid metabolism and evaluated the ability of placenta to mobilize lipids. Fourteen gilts were divided into two groups of seven and fed a diet containing 15% tallow diet or a diet not supplemented with tallow (control) from d 90 to 110 of gestation. Dietary lipid had no detectable effects on lipoprotein lipase activity, [14C]palmitate metabolism, or lipolysis by the maternal or fetal placenta. Lipolytic activity of placental tissues was minimally affected by incubation with various proposed lipolytic activity of placental tissues was minimally affected by incubation with various proposed lipolytic agents. The data indicate that supply of fatty acids to the fetal pig may be limited by transfer of plasma fatty acids into the cytoplasm of placental cells or by regulatory enzymes for intermediate esterification; both types of limitations have been proposed to be influenced by fatty-acid binding proteins. PMID- 1938648 TI - Ultrasonic, needle, and carcass measurements for predicting chemical composition of lamb carcasses. AB - Three groups (n = 147) of New Zealand mixed breed lambs averaging 170 d of age and 31.7 kg in weight were killed after a diet of pasture to determine whether the total depth of soft tissues over the 12th rib 11 cm from the dorsal midline (GR) could be measured in live lambs with sufficient accuracy to warrant its use as a selection tool for breeding flock replacements. Relationships among live and carcass measurements and carcass chemical composition also were determined. An ultrasonic measurement of GR in the live lambs was a more accurate predictor of carcass GR (r = .87) and percentage carcass fat (r = .80) than was a measurement of GR made with a needle (r = .80 and .67, respectively). Both measurements were sufficiently accurate to permit culling of over-fat lambs from breeding flock replacement prospects. The best single indicator of percentage carcass fat (r = .87) was a shoulder fat measurement, followed closely by carcass GR (r = .85). Both were superior to USDA yield grade for estimating carcass chemical composition in these young, lightweight lambs. These two measurements also were most highly related to percentage carcass protein (r = -.78 and r = -.77, respectively). These results indicate possibilities for improving the method of evaluating the composition of U. S. lamb carcasses. PMID- 1938649 TI - Growth, carcass traits, and fatty acid profiles of adipose tissues from steers fed whole cottonseed. AB - To investigate the impact of dietary whole cottonseed (WCS) level on fatty acid composition, growth, and carcass traits, 45 Hereford steers were assigned to diets containing 0, 15, or 30% dietary WCS. The 15 and 30% WCS contributed an estimated 3.3 and 6.6% additional lipid, respectively, to the diets. After being fed for 54 d, all animals were weighed and slaughtered, and carcass measurements were obtained. There were no differences (P greater than .05) among dietary treatment groups in live weight or ADG for the 54-d feeding period. Control steers had larger (P less than .05) longissimus muscle areas than steers fed 30% WCS, which accounted for the advantage in yield grade (P less than .05) exhibited by the control group. Feeding of 30% WCS resulted in minor increases in linoleic and total polyunsaturated fatty acid content of perinephric fat expressed in both normalized (area percentage) and gravimetric (g/100 g of fresh tissue) formats. There were no significant differences in the monounsaturated or saturated fatty acid content of adipose tissues from animals fed the different diets. Subcutaneous adipose tissue samples were higher (P less than .01) in total unsaturates but had lower (P less than .05) proportions of C18:0 and C18:1 than perinephric samples. Feeding WCS at the levels reported herein only had minor effects on fatty acid composition of beef adipose tissues. PMID- 1938650 TI - The effect of breed of sire and age at feeding on muscle tenderness in the beef chuck. AB - Steers (n = 59) produced from the mating of Braford, Simbrah, Senepol, and Simmental bulls to Brahman- and Romana Red-sired cows and Brahman bulls to Angus cows were used in this study. Effects of sire breed and age at feeding on muscle tenderness in the major muscles of the chuck when steers were fed to 1.0 cm 12th rib fat were determined. There were no muscle tenderness effects due to sire breed group, with the exception of the serratus ventralis muscle, which was more tender in Brahman- and Braford-sired steers than in Simmental-sired steers. Additionally, the supraspinatus muscle from the yearlings was lower in shear value than that from the calves. The Brahman-sired steers had serratus ventralis muscles with higher percentages (P less than .05) of intramuscular fat than those of Braford-, Simbrah-, and Simmental-sired steers. Fat deposited within the muscle or between muscles in the chuck was not related to muscle tenderness as measured by Warner-Bratzler shear values. Also, percentages of intramuscular fat of the triceps brachii, serratus ventralis, or supraspinatus muscles were not influenced (P greater than .05) by age at feeding. PMID- 1938651 TI - Impact of dietary tryptophan and behavioral type on growth performance and plasma amino acids of young pigs. AB - Tryptophan (TRP) content in the protein of the weaning diet was varied from deficient (.70 g/16 g N) to adequate (1.15 g/16 g N) and excess (1.60 g/16 g N) in diets fed to 108 pigs from d 5 to d 26 after weaning (W) and in 72 pigs from d 26 after weaning to slaughter (100 kg live weight) to assess immediate and long term effects of TRP on performance. Daily weight gain and feed efficiency were improved when dietary TRP was increased from deficient to adequate (+60 and +40%, respectively). Concurrently, daily feed intake was elevated moderately (+15%). No further improvement was observed with excess TRP. In the low TRP group, gain/feed was significantly poorer up to 25 kg live weight, but this effect did not continue later. Although no compensatory growth could be shown in the group fed the deficient diet, growth retardation was very small (1.5%; P greater than .10) at slaughter. Early changes in TRP supply did not affect either carcass or meat quality. Behavioral reactivity, as determined on day W + 5 in an "open-field" test, did not affect early performance, but growth rate during the growing finishing stage (3.2%) or the whole period (2.5%) was greater by nonemotional than by emotional pigs. Plasma amino acid contents in blood samples, withdrawn on day W + 15 (fed state) and W + 17 (fasted state), were consistent with the effect of TRP on growth rates. However, in the fasted state, a diet x reactivity interaction suggested that TRP removal from the plasma was less rapid in nonemotional than in emotional pigs. Furthermore, increased plasma concentrations of essential amino acids and urea in the latter group suggested that protein and amino acid catabolism was more rapid in emotional than in nonemotional pigs. These data are discussed relative to the effect of the behavioral type of pig on its TRP requirement. PMID- 1938652 TI - Effects of metoclopramide on steers fed Kochia scoparia hay. AB - Kochia hay that had elicited mild toxicosis in sheep and cattle when fed for 21 d was fed to young, growing steers to evaluate the efficacy of metoclopramide for preventing kochia toxicosis. Twelve steers (271 +/- 39 kg) were given ad libitum access to Kochia hay for 38 d. Six steers were dosed orally with 15 mg of metoclopramide/kg of BW three times each week in gelatin capsules, and six steers received empty gelatin capsules. Steers were housed in individual outside pens for the first 28 d, then inside in metabolism stalls for the last 10 d. Kochia intake averaged 1.2 +/- .04 and 1.1 +/- .05% of BW throughout 38 d for kochia-fed control and kochia plus metoclopramide-dosed steers, respectively. During the last 10 d, metoclopramide had no effect (P greater than .15) on digestibility of DM, OM, NDF, ADF, or CP. However, metoclopramide reduced N retention (P less than .01; 20 vs 8 g/d). Kochia hay decreased serum prolactin and insulin concentrations (P less than .01) from 12.4 to 1.5 ng/ml and from .53 to .23 ng/ml, respectively. Metoclopramide had no effect (P greater than .50) on prolactin or insulin in steers fed kochia hay. Serum growth hormone was not affected by kochia but was suppressed by metoclopramide in steers fed kochia hay (P less than .07). Serum bilirubin (total and unconjugated) was elevated (P less than .05), indicating early, mild hepatotoxicosis characteristic of kochia toxicosis. Kochia also increased serum concentrations of iron, total protein, albumin, globulin, and creatinine and decreased urea N (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938653 TI - Effect of a hay and a grain diet on the rate of hydrolysis of ochratoxin A in the rumen of sheep. AB - The hydrolysis of ochratoxin A (OA) and the corresponding formation of its hydrolysis product, alpha ochratoxin (O alpha), by ruminal digesta and in the rumen of hay-fed and grain-fed sheep were compared. Ruminal contents from sheep fed diets with hay or with grain hydrolyzed OA in vitro; the majority of the activity was associated with the particulate fraction of the ruminal contents. The rate of hydrolysis of OA by ruminal fluid that was adjusted to different pH values was not influenced (P greater than .6) by the pH of the samples (pH was from 5.5 to 7.0). Ruminal fluid obtained from hay-fed animals (pH 7.0) was able to hydrolyze OA in vitro and to produce the hydrolyzed product, O alpha, at a much greater rate (fivefold) than ruminal fluid obtained from grain-fed animals (pH 5.5) (P less than .01). Ochratoxin A was administered intraruminally at a concentration of .5 mg/kg of BW to hay-fed and grain-fed sheep. The half-lives for disappearance of OA from the rumen of sheep fed grain (normal feed intake, rumen pH 5.7), fed grain at a low level (30% of normal feed intake, pH 6.5), and fed hay (pH 7.1) were 3.6, 1.3, and .6 h, respectively. The results suggest that OA is hydrolyzed much faster in the rumen of sheep fed hay than in sheep fed grain, presumably because of the different ruminal microbial population, which in turn influenced the rate of hydrolysis of OA. PMID- 1938654 TI - Effect of a hay and a grain diet on the bioavailability of ochratoxin A in the rumen of sheep. AB - The role of the rumen and its contents in the detoxification of ochratoxin A (OA) was studied in sheep. The first experiment established that very little conversion of OA to alpha ochratoxin (O alpha) occurs systematically; 90 to 97% of the OA and metabolites was recovered as unaltered OA in the urine. Most of the small amount of O alpha recovered was also in the urine. In this experiment, two sheep were fasted and another two fed normally, but feed intake had no significant effect. In the second experiment, two sheep fed hay and two fed grain were dosed with OA at .5 mg/kg of BW into the rumen via a cannula. Recoveries, in urine and feces, accounted for 58 to 70% of the administered OA, but almost all (greater than 97%) was in the form of O alpha. About 76 to 92% of this O alpha was in the urine. Although excretion patterns and pharmacodynamics tended to differ with different diets, one of the sheep fed grain had very low intake and the results were equivocal. In the third experiment, eight sheep (four fed hay, four fed grain) were given a single intraruminal dose of OA (.5 mg/kg of BW). The disappearance of OA from the rumen and the corresponding formation of O alpha was much faster for hay-fed than for grain-fed sheep; the half-lives were .63 and 2.7 h for OA and .9 and 1.9 h for O alpha, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938655 TI - Plasma concentrations of cortisol, prolactin, luteinizing hormone, and follicle stimulating hormone in stallions after physical exercise and injection of secretagogue before and after sulpiride treatment in winter. AB - Ten lighthorse stallions were used to determine 1) whether prolactin (PRL) and cortisol responses previously observed after acute exercise in summer would occur in winter when PRL secretion is normally low, 2) whether subsequent treatment with a dopamine receptor antagonist, sulpiride, for 14 d would increase PRL secretion and response to thyrotropin-releasing hormone (TRH) and exercise, and 3) whether secretion of LH, FSH, and cortisol would be affected by sulpiride treatment. On January 11, blood samples were drawn from all stallions before and after a 5-min period of strenuous running. On January 12, blood samples were drawn before and after an i.v. injection of GnRH plus TRH. From January 13 through 26, five stallions were injected s.c. daily with 500 mg of sulpiride; the remaining five stallions received vehicle. The exercise and secretagogue regimens were repeated on January 27 and 28, respectively. Before sulpiride injection, concentrations of both cortisol and PRL increased (P less than .05) 40 to 80% in response to exercise; concentrations of LH and FSH also increased (P less than .05) approximately 5 to 10%. Sulpiride treatment resulted in (P less than .05) a six- to eightfold increase in daily PRL secretion. The PRL response to TRH increased (P less than .05) fourfold in stallions treated with sulpiride but was unchanged in control stallions. Sulpiride treatment did not affect (P greater than .05) the LH or FSH response to exogenous GnRH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938656 TI - Influence of daily injections of porcine somatotropin on growth, puberty, and reproduction in gilts. AB - To determine whether recombinant porcine somatotropin (rpST) alters reproduction, 40 crossbred gilts weighing 59.1 +/- .5 kg at 125 +/- 1 d of age were assigned randomly to an experiment arranged as a 2 x 2 factorial. Eight gilts were given daily injections of diluent until they reached 104 kg BW (DW), and eight received diluent injections until puberty (DP). Twelve gilts were given rpST (4 mg/d) until 104 kg BW (PW) and 12 were given rpST injections until puberty (PP). All gilts were individually fed on an ad libitum basis an 18% CP corn-soybean meal diet (1.2% lysine and 3.1 Mcal/kg of ME). Beginning at 5 mo of age, gilts were exposed 20 min daily to mature boars. Serum concentrations of progesterone were measured weekly from 5 to 8 mo of age to verify age of puberty. Gilts observed in pubertal estrus were mated to two different boars 10 h apart. At 47 +/- 1 d of gestation, gilts were slaughtered to assess fetal development. After 60 d of treatment, serum LH and FSH profiles were determined in blood samples drawn at 20 min intervals for 4 h from eight diluent- and eight rpST-treated gilts fitted with indwelling jugular catheters. By 28 d, feed intake, feed/gain, and blood urea nitrogen were decreased (P less than .005) by rpST. Treatments did not affect (P greater than .05) the proportion of gilts attaining first ovulation (DW = 6/6; DP = 10/10; PW = 7/9; PP = 14/14) or conception rate (DW = 5/6; DP = 7/10; PW = 4/6; PP = 11/12).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938657 TI - Influence of dietary energy on follicular development, serum gonadotropins, and first postpartum ovulation in suckled beef cows. AB - Twenty-eight Hereford x Angus cows (4 yr of age) were used to determine the effects of pre- and postpartum dietary energy on performance and reproductive function in suckled beef cows. The experiment was designed as a 2 x 2 factorial with cows receiving either 70 (L) or 150% (H) of NRC recommended level of dietary energy before and(or) after parturition, resulting in four treatment combinations (L-L, L-H, H-L, H-H). Prepartum diets were fed for approximately 110 d, and postpartum diets were fed until either 10 d after the second postpartum ovulation or 150 d postpartum for those cows that failed to ovulate. Cows receiving low compared with high levels of energy before calving lost more (P less than .01) weight, body condition, subcutaneous fat, and longissimus muscle area before parturition and had calves with lighter (P less than .01) birth weights. Cows receiving low compared with high levels of energy postpartum lost more (P less than .01) weight, body condition, and longissimus muscle area after parturition. Low levels of energy before and after parturition decreased (P less than .01) milk production and calf weight at 70 d of age. Rates of cervical and uterine involution were unaffected by dietary energy treatments. Cows receiving high levels of energy prepartum had increased (P less than .01) mean concentrations and pulse frequency of LH in serum after parturition, and cows receiving high levels of energy postpartum had increased (P less than .05) pulse frequency of LH. Low levels of energy postpartum decreased (P less than .01) appearance rate of small (5.0 to 7.9 mm) and large (greater than or equal to 10 mm) follicles, and low levels of energy prepartum decreased (P less than .02) appearance rate of large follicles based on transrectal ultrasonography. Cows receiving high levels of energy prepartum had shorter (P less than .02) intervals from parturition to ovulation, and a higher (P less than .01) percentage of the cows that received high levels of energy postpartum ovulated by 150 d postpartum. In summary, prepartum level of dietary energy influenced birth weight and weight gain of calves, milk production, concentrations and pulse frequency of LH in serum, appearance rate of large follicles, and the interval to first ovulation. Postpartum level of dietary energy influenced milk production, weight gain of calves, pulse frequency of LH, appearance rate of small and large follicles, and the percentage of cows that ovulated after parturition. PMID- 1938658 TI - Ovarian morphological conditions and the effect of injection of human chorionic gonadotropin on ovulation rates in prepuberal gilts with two morphologically different ovarian types. AB - The purpose of this experiment was to determine the ovulation rate after treatment with human chorionic gonadotropin (hCG) in two groups of gilts characterized by different ovarian morphology: grape-type (GT; n = 11) and honeycomb-type (HT; n = 7). At 170 d of age (d 0), gilts were examined by laparoscopy and ovarian type was determined by the distribution of macroscopic follicles present on the ovarian surface. Five to ten minutes after surgery, each gilt received a single injection (i.m.) of 750 IU of hCG. At d 0, GT ovaries had a greater number of large follicles (greater than or equal to 6 mm) than HT ovaries (10.0 +/- .5 vs 2.6 +/- .3; P less than .05), whereas HT ovaries had more small follicles (1 to 3 mm; HT: 42.3 +/- .8 vs GT: 26.7 +/- .9; P less than .05) and total follicles (HT: 59.4 +/- 2.3 vs GT: 52.2 +/- 1.5; P less than .05), although numbers of medium follicles (4 to 5 mm) were similar (GT: 15.6 +/- .8 vs HT: 14.6 +/- 1.7; P greater than .10). Number of induced corpora lutea (CL) per ovary was greater (P less than .05) in gilts with GT ovaries (10.59 +/- 2.9 CL) than in gilts with HT ovaries (5.21 +/- .66 CL). Total weight of luteal tissue (LT) per ovary and serum progesterone concentrations 8 d after induction of ovulation were greater in GT gilts than in HT gilts (GT: 6.37 +/- 1.09 g vs HT: 3.31 +/- .49 g for LT, P less than .05; GT: 21.08 +/- 4.76 ng/ml vs HT: 13.40 +/- 2.05 ng/ml for progesterone, P less than .07).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938659 TI - Effects of methionine hydroxy analog on voluntary intake, digestibility, nitrogen balance, and chewing behavior in sheep fed grass silage. AB - Voluntary intake, digestibility, N balance, and chewing behavior of six 6-mo-old (young) and six 30-mo-old (mature) Texel wethers (32.6 and 83.1 kg average BW) given ad libitum access to grass silage and 100 g of top-dressed soybean meal with or without 5 g of methionine hydroxy analog (MHA) in the acid form were examined according to a two-period crossover design. Supplementation level of MHA in the acid form corresponded to .32 and .16 g of MHA/kg BW.75, respectively, in young and mature wethers. There was no effect (P greater than .10) of MHA on mean voluntary DMI. Methionine hydroxy analog supplementation increased (P less than .02) digestibility of DM, OM, and CP by young wethers but not (P greater than .18) by mature wethers. The MHA decreased eating time (P less than .03) in both young and mature wethers and intake level (P = .01) in young wethers during the first 1.5 h of access to grass silage. With MHA, both age groups increased (P less than .05) the daily number of meals and decreased (P less than .02) the mean duration of each meal. There was no effect (P greater than .06) of MHA on daily and unitary eating, ruminating, and masticating times; however, mean duration of consecutive rumination bolus cycles was longer (7.2%; P = .01) in young wethers. Young vs mature sheep ate more (53.4 vs 39.3 g of DM/[d.kg BW.75]; P less than .001) and had shorter unitary mastication times (P = .001). Results suggest that, depending on its relative level of supplementation, MHA in the acid form could act through both palatability and effects on ruminal metabolism. PMID- 1938660 TI - Image analysis and nonlinear modeling to determine dimensions of wet-sieved, masticated forage particles. AB - A procedure to estimate dimensions of digesta particles was developed and evaluated. After wet sieving, particles of masticated switchgrass and bermudagrass hays retained on sieves with apertures of 1.0 mm2 or larger were placed on moist white filter paper, separated manually, and photographed. Photographs were scanned with a flat-bed scanner, scaled to size, and digitized. Projected area, perimeter, length, and width of particles were determined by a microcomputer system. Variables derived for each particle included the form factor, which was defined as (4 x pi x area)/perimeter2, and each particle's length: width ratio. Ninety-three percent of data from two trials with steers had significant lack of fit (P less than .05 to P less than .0001) to normal, lognormal, Weibull, or gamma distributions. As an alternative, individual particle measurements were summed on a cumulative percentage basis for each variable and were fit to an inverted Gompertz function to estimate median, mode, and mean dimensions of scanned particles. Estimates from the equation fit the distribution well; asymptotic SE averaged 3.5 and 1.4% of parameter means for dimensions of masticated switchgrass and bermudagrass hay particles, respectively. No analytic solution exists for the mean, which must be estimated numerically, but analytic solutions are available for the median and mode. Use of this equation will prevent bias caused by lack of fit to a particular distribution and yield more accurate estimates of mean particle dimensions than arithmetic means. PMID- 1938661 TI - Utilization of sulfur and other mineral elements by growing dairy heifers treated with bovine somatotropin. AB - Apparent absorption and retention of Ca, P, Mg, K, Cu, Mn, Zn, and S were determined in Holstein heifers treated with recombinant bovine somatotropin (bST). Six heifers (initial BW averaged 104 kg) were assigned to various doses of bST in a 6 x 6 Latin square design with six consecutive 21-d periods. Treatments were daily i.m. injections of 0, 6.7, 33.3, 66.7, 100, or 200 micrograms of bST/kg of BW on d 8 to 21 of each period. All heifers were fed a hay-concentrate diet, and nutrient digestibilities and balances were determined on d 14 to 20 of each period. Mineral concentrations in feed, water, excreta, and blood plasma were determined with an inductively coupled argon plasma-emission spectrometer. Exogenous bST did not affect apparent absorption or retention of Ca, P, Mg, K, Cu, Mn, or Zn. Plasma CU concentration was greater (P less than .05) in heifers receiving bST (82 micrograms of Cu/dl) than in those receiving excipient (73 micrograms of Cu/dl); plasma concentrations of other elements were not affected by bST. Injection of bST did not affect S absorption, but urinary S excretion decreased (P less than .05) and S retention increased (P less than .05) as dose of bST increased. The amount of S retained (1.5 g/d) when the heifers received the largest dose of bST was approximately 50% greater than the amount retained when heifers received excipient. These results demonstrate that bST affects the postabsorptive metabolism of S. Generally, bST did not affect nutrient digestibilities. Effects of bST on dietary mineral requirements were not determined because of the relatively short (14 d) treatment periods. PMID- 1938662 TI - Supplemental fat in high-energy rations for lactating cows: effects on intake, digestion, milk yield, and composition. AB - Supplemental fats (SF) have special value in the diets of dairy cows with superior productive ability, because the high energy density of SF allows greater energy consumption and direct transfer of the fatty acids (FA) of the SF to milk fat; this increases metabolic efficiency. Some SF, especially oils with a high degree of unsaturation, disturb ruminal fermentation, decrease fiber digestibility, and lower milk fat test; however, oilseeds (e.g., whole cottonseed) can be fed without observable ruminal inhibition, probably because of a slow release of the oil into ruminal contents. A number of commercial fat supplements are available that have little effect on ruminal fermentation and are highly digestible postruminally. A product of the calcium salts of palm oil fatty acids was shown to have a NE for lactation of more than three times that of corn. As the emphasis in milk pricing formula changes from milk fat to milk protein, there is greater concern regarding the propensity of fat supplements to decrease milk protein (casein) percentage. In two studies, a supplement of ruminally protected lysine and methionine largely prevented the reduction in casein percentage that occurred with feeding SF, indicating that the amino acid profile of undegraded dietary protein is important with regard to preventing the lower casein percentage. Combining fat supplements that are slowly released in the rumen with those that are inert in the rumen will allow maximal use of SF. PMID- 1938663 TI - Effects of dietary fat on metabolic disorders and reproductive performance of dairy cattle. AB - Improved reproductive performance and reduced incidence of metabolic disorders have been postulated to be benefits of feeding supplemental fat to dairy cows. Increased plasma nonesterified fatty acid concentrations during fat supplementation may result from incomplete tissue uptake of fatty acids after lipoprotein lipase hydrolysis of very-low-density lipoprotein triglyceride; however, evidence suggests that net adipose tissue triglyceride hydrolysis may be increased during fat supplementation. Plasma 3-OH-butyrate concentrations remain relatively constant during fat supplementation but may have a tendency to be reduced if fat is supplemented to cows having relatively high basal plasma 3-OH butyrate concentrations. Because plasma ketone levels usually increase when nonesterified fatty acid concentrations are elevated, it is hypothesized that potential antiketogenic effects of added fat are due to a glucose sparing effect. Supplemental fat does not seem to reduce hepatic lipid infiltration near the time of calving. Potential mechanisms by which supplemental fat may improve reproductive performance include stimulation of prostaglandin F2 a synthesis and secretion and enhanced utilization of blood cholesterol for progesterone synthesis. Days postpartum until first ovulation and luteal function of dairy cattle have been related to energy balance during the first 3 wk postpartum. Energy balance data for early lactation cows fed supplemental fat are not plentiful; however, slight but statistically nonsignificant increases have been observed when feeding fat. Cows fed supplemental fat that experience improved energy balance may begin to cycle sooner because of enhanced follicular growth and development. Applied studies examining the effects of supplemental fat on reproductive performance have provided inconsistent results. PMID- 1938664 TI - National genetic improvement programs for dairy cattle in the United States. AB - Rate of genetic improvement for milk yield has been increasing in recent years. Cows born in 1986 were about 135 kg superior in breeding value for milk yield to those born in 1985. Over 2.2 million cows contribute new data to genetic evaluations for production traits annually. These evaluations are computed with an animal model that provides best linear unbiased predictions of transmitting abilities for milk, fat, and protein yields and fat and protein percentages. The model includes effects of management group, permanent environment, herd-sire interaction, and animal genetic merit. Unknown-parent groups represent the genetic merit of base populations defined by birth year and sex. Type appraisal data are collected by breed associations and are evaluated with a sire model. Holstein cow evaluations are computed using scores from all appraisals and a multitrait model; evaluations for other breeds are computed using all appraisal scores, a repeatability model, and a single-trait system. Dystocia data are collected by individual AI organizations and dairy records processing centers; they are analyzed by a categorical-trait sire model at Iowa State University with support from the National Association of Animal Breeders. The AI organizations have been extremely important in increasing rate of genetic progress by increasing numbers of young bulls sampled, increasing selection intensity of bull dams through multiple ovulation and embryo transfer, and shortening generation interval through the use of younger cows and some virgin heifers as bull dams. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938665 TI - An overview of beef cattle improvement programs in the United States. AB - A periodic review of beef improvement programs is useful as a benchmark and as an opportunity to reevaluate industry direction. The history of improvement programs is reviewed with particular emphasis on recording organizations, program financing, and technological progress. The various breed associations have become the primary suppliers of performance programs, which are largely funded through registration income. Current practices are described from the aspects of traits recorded and delivery systems to collect, analyze, and distribute the data. The unique or innovative features of several breed made of the organization, technical, and educational challenges facing beef improvement. Although increased participation in genetic improvement programs is expected, substantial efforts are needed to serve adequately the needs of a changing beef cattle industry. PMID- 1938666 TI - The National Sheep Improvement Program: a review. AB - A nationally organized sheep improvement program for sheep producers in the United States was implemented in 1987 under the name of the National Sheep Improvement Program (NSIP). This program completed a 3-yr Phase I project on February 16, 1990, that involved the definition of a uniform set of performance guidelines, development of an NSIP records processing center with associated performance recording materials and computer software, and the enrollment of both purebred and commercial flocks. Organizers of the NSIP have defined 12 traits of economic importance to the U.S. sheep industry for genetic evaluation: number of lambs born, total ewe productivity, six growth traits, and four wool traits. Genetic evaluations are currently being conducted on a within-flock basis and will move to an across-flock, within-breed basis when sufficient genetic ties between flocks are established. The genetic evaluations use BLUP procedures and provide genetic merit values in the form of expected progeny differences for every animal in a flock. PMID- 1938667 TI - Genetic improvement programs in livestock: swine testing and genetic evaluation system (stages). AB - Genetic evaluations for the U.S. swine industry are conducted by the eight purebred associations of the National Association of Swine Records. Within-herd evaluations of the growth traits (days to 105 kg [market] and backfat depth) were first reported in 1986. Analyses of the maternal traits (litter size at birth and weaning, and litter 21-d weight) were inaugurated in 1987. Expected progeny differences (EPD) are reported for all traits and for general, paternal, and maternal bioeconomic indexes. A sow productivity index combining only maternal traits is available. All records are adjusted according to National Swine Improvement Federation (NSIF) guidelines for effects such as number of pigs transferred at crossfostering and age at recorded observation prior to the BLUP evaluation. Within-herd analyses of individual contemporary groups are conducted immediately on receipt of performance records at each breed association office. All parents in the herd and the young pigs in the current group are evaluated. A report is returned to the breeder for use in herd selection and the EPD are placed in the pedigree file. The genetic base of each herd is defined as the first n tested pigs or litters, where n is the number of pigs registered annually within the herd. Change in mean EPD between groups is indicative of genetic trend. Periodic across-herd analyses are used to update interim within-herd analyses and a national sire summary is published. PMID- 1938668 TI - Genetic predictions of racing performance in quarter horses. AB - Research on the racing performance of quarter horses has been used to develop genetic prediction summaries on all horses with at least one start on record at the American Quarter Horse Association. In the 1987 summary, records from a total of 212,065 horses were used to give genetic predictions on stallions, mares, geldings, fillies, and colts. A reduced animal model was used that incorporated the repeated records of individuals. The individual race was the contemporary group after the data were adjusted for distance, sex, and age. Estimates of heritability of .24 and repeatability of .32 suggest that increased racing performance can be achieved if the predictions are used by breeders. Continued research in variance component estimation includes the genetic covariances among the several distances, maternal influence, and genetic parameters for racing longevity. PMID- 1938669 TI - The control and consequences of bacterial fermentation in the human colon. PMID- 1938670 TI - A simplified key for identifying homofermentative Lactobacillus and Carnobacterium spp. from meat. AB - Species of Lactobacillus and Carnobacterium from meat and meat products could be separated by a few biochemical characteristics; presence of meso-diaminopimelic acid in the cell wall, the isomers of lactic acid produced, production of citrulline from arginine and fermentation of some carbohydrates. This identification key was checked by DNA-DNA hybridizations studies. PMID- 1938672 TI - The lethal effect of carrot on Listeria species. AB - When shredded or sliced carrots were inoculated with Listeria monocytogenes the number of viable listerias decreased rapidly. On carrot slices stored at 8 degrees C there was a decrease after 3d followed by an increase, after 7d, to numbers similar to those present initially. The numbers of spoilage micro organisms increased throughout storage at 8 degrees C. Carrots macerated in a Stomacher Lab Blender also showed an antilisterial activity which resulted in a decrease in number of viable bacteria and in sublethal damage. The effect was shown by five carrot cultivars and acted on nine strains of L. monocytogenes and single strains of L. innocua, L. ivanovii, L. seeligeri, L. melshimeri. This antilisterial effect was heat-labile, was inactivated after a few hours at 4 degrees C or at 30 degrees C and was active over the pH range 5.8 to 7.0. Maceration of carrots in an Atomix blender for 1 min or in liquid nitrogen destroyed the antilisterial activity. PMID- 1938671 TI - Behaviour of Listeria monocytogenes in meat and its control by a bacteriocin producing strain of Lactobacillus sake. AB - Lactobacillus sake Lb 706 can release a bacteriocin inhibitory to Listeria monocytogenes. In MRS broth, viable counts decreased rapidly when Lact. sake Lb 706 was added, whereas growth of the listerias was not affected by a bacteriocin negative variant of the same Lactobacillus strain. Inhibition of L. monocytogenes was also observed in pasteurized minced meat inoculated with Lact. sake Lb 706. The bacteriocin produced is apparently effective in meat. However, the effect of the bacteriocin producer was less evident in minced meat than in broth. In comminuted cured raw pork filled into casings (German-type 'fresh Mettwurst'), L. monocytogenes was able to grow at a pH of 6.3, but addition of Lact. sake Lb 706 prevented the growth of listerias during the first few days after manufacture. At normal pH (5.7) L. monocytogenes did not multiply and addition of Lact. sake Lb 706 reduced viable counts of listerias by about one log cycle. Lactobacillus sake Lb 706 therefore may have some potential as a protective culture in meat products. PMID- 1938673 TI - Thermal inactivation of Listeria monocytogenes during a process simulating temperatures achieved during microwave heating. AB - Conventional heating was used to expose cells of Listeria monocytogenes, either in broth or in situ on chicken skin, to the mean times and temperatures that are achieved during a 28 min period of microwave cooking of a whole chicken. Heating L. monocytogenes by this method in culture broth resulted in a reduction in viable cell numbers by a factor of greater than 10(6) upon reaching 70 degrees C. Simulated microwave cooking of L. monocytogenes in situ, on chicken skin, resulted in more variability in the numbers of survivors. Heating for the full cook time of 28 min, however, resulted in a mean measured temperature of 85 degrees C and no surviving listerias were detected. This indicated a reduction in viable numbers of greater than 10(6). To reduce temperature variation, cells were heated on skin in a submerged system in which exposure to 70 degrees C for 2 min resulted in a reduction in viable cell numbers of all strains of listerias tested of between 10(6) and 10(8). These results show that when a temperature of 70 degrees C is reached and maintained for at least 2 min throughout a food there is a substantial reduction in the numbers of L. monocytogenes. The survival of this organism during microwave heating when temperatures of over 70 degrees C are reported is probably due to uneven heating by microwave ovens resulting in the presence of cold spots in the product. The heat resistance of L. monocytogenes is comparable with that of many other non-sporing mesophilic bacteria. PMID- 1938674 TI - Removal of faecal indicator bacteria and bacteriophages from the common mussel (Mytilus edulis) under artificial depuration conditions. AB - Artificial self-purification (depuration) of mussels (Mytilus deulis) was undertaken at three temperatures, under conditions similar to those likely to be experienced in the commercial shellfish industry of the UK. During a 72 h depuration period, samples of mussel flesh were examined for three faecal indicator bacteria, Escherichia coli, Group D faecal streptococci and sulphite reducing Clostridium spores, and two types of bacteriophage. There was a statistically significant difference in the elimination rate of faecal indicator bacteria compared with the slower rate for both bacteriophages. PMID- 1938675 TI - Decreased DNA damage by acid and increased repair of acid-damaged DNA in acid habituated Escherichia coli. AB - A study of the conjugal transfer of ColV,I-K94 tn 10 from acid-treated donors suggested that acid-habituated recipients repair acid-damaged plasmid DNA better than those that are not habituated. The presence of an increased repair activity for acid-damaged DNA in habituated cells was confirmed by isolating pBR322 from acid-treated organisms; habituated cells produced more transformants when transformed by it than did non-habituated ones. Additionally, agarose gel electrophoretic studies of pBR322 DNA isolated from acid-damaged cells and tests of its transforming activity both indicated that plasmid DNA in habituated cells is less damaged by extreme acidity than is that in non-habituated organisms. PMID- 1938677 TI - A note on the isolation of psychrotrophic coliform organisms from faecal-polluted environments. AB - The Simmons citrate salicin (SCS) medium was developed for the enrichment and isolation of presumptive psychrotrophic coliforms from polluted environments. The selectivity and resolution of the medium were tested with pure and mixed laboratory cultures. A procedure for the isolation of psychrotrophic coliforms from polluted environments using a lactose-bile broth and SCS medium is presented. PMID- 1938676 TI - Establishment in the piglet gut of lactobacilli capable of degrading mixed-linked beta-glucans. AB - The establishment in piglets of lactobacilli with ability to degrade mixed-linked (1----3), (1----4) beta-D-glucans was studied in faeces from 15 animals. The piglets had free access to creep feed with an estimated content of 2% beta-D glucans from 5 days of age. On days 3 and 35, ca log 8 cfu/g of beta-glucan degrading lactobacilli were found in a majority of the samples. On days 7, 14 and 21 such bacteria were only found occasionally. During establishment of the microflora in the neonate, the faecal lactobacilli of the piglet seemed related to those of the sow. Later, the metabolic activity of the lactobacilli in piglet faeces showed a connection to the composition of the diet. The possible relation of these bacteria to occurrence of beta-glucanases attributed to be endogenous in the pig is discussed. PMID- 1938678 TI - Enumeration by a miniaturized method of Escherichia coli, Streptococcus bovis and enterococci as indicators of the origin of faecal pollution of waters. AB - Counts of Escherichia coli, faecal streptococci and enterococci were made on faecal specimens from human and animal origin and urban raw sewage waters, with microtiter plates containing selective substances. Escherichia coli was more numerous than faecal streptococci and enterococci in 80% of the samples regardless of the origin. Consequently the use of the ratio E. coli/faecal streptococci to distinguish human from animal origin of faecal pollution is questionable. Enterococcus faecalis was predominant in human and poultry faeces, Streptococcus bovis was typical of the bovine faeces and to a lesser extent also of pig faeces whereas Enterococcus durans, Ent. hirae and Ent. faecium did not characterize any faecal source. Streptococcus bovis could be distinguished in the microtiter plate by its inability to reduce triphenyl tetrazolium chloride (TTC) in the medium. PMID- 1938679 TI - From accuracy towards truth: the BSAC Working Party's guide to sensitivity testing. PMID- 1938680 TI - From foreign pharmacopoeias: 'new' antibiotics from old? PMID- 1938681 TI - Cloning of the type Ib trimethoprim-resistant dihydrofolate reductase gene and preparation of a specific biotinylated DNA probe. AB - A 3.0-kb PstI/HindIII fragment encoding the type Ib trimethoprim-resistant dihydrofolate reductase (DHFR) was cloned into pUC18. Following successive subcloning, the type Ib DHFR gene was identified within a 500 bp HincII fragment. The 500 bp fragment was purified, biotinylated and tested for its suitability as a specific DNA probe in non-isotopic hybridisation experiments with standard plasmids carrying genes for the available known Gram-negative DHFR types. Under conditions of high stringency the probe was specific for the type Ib gene and hence will be useful for monitoring the spread of this particular trimethoprim resistance gene. PMID- 1938682 TI - Susceptibility of Bacteroides ureolyticus to antimicrobial agents and identification of a tetracycline resistance determinant related to tetM. AB - The in-vitro activity of ten antimicrobial agents was evaluated for 28 clinical isolates of Bacteroides ureolyticus, an obligate anaerobe associated with non gonococcal urethritis. The isolates were characterized by plasmid DNA profile and PAGE protein pattern. All isolates were inhibited at concentrations equal to or lower than the recommended breakpoint concentration for ampicillin (16 mg/l), metronidazole (16 mg/l) and erythromycin (4 mg/l). Twenty-seven isolates were inhibited by less than or equal to 2 mg/l of ciprofloxacin, pefloxacin and ofloxacin. Four isolates were tetracycline-resistant requiring 2-64 mg/l of tetracycline, minocycline or doxycycline for inhibition. In two tetracycline resistant isolates tetM was demonstrated by dot-blot and Southern hybridizations. These two isolates did not contain a plasmid and had a PAGE protein pattern type III. These data confirm the spread of the tetM determinant in various bacteria of the genital tract. PMID- 1938683 TI - Factors influencing the uptake of norfloxacin by Escherichia coli. AB - The effect of cyanide, arsenate, Mg++ or EDTA on the uptake of norfloxacin in Escherichia coli was measured. Uptake of norfloxacin was suppressed by either 0.1 mM MgSO4 or 0.1 mM EDTA, while the presence of 0.1 mM MgSO4 increased the minimum suppressive concentration of EDTA from 0.1 to 0.2 mM. Increased uptake in the presence of 10 mM cyanide was observed, but the addition of 10 mM arsenate had no significant effect. Concentration of norfloxacin in bacterial cells was observed even when uptake was suppressed by the addition of 10 mM EDTA. Uptake in mini cells was comparable to that in whole cells. These results suggest that the uptake of norfloxacin in E. coli, in addition to influx by simple diffusion and energy-dependent efflux, is influenced by binding of norfloxacin to the cell surface as a result of chelating activity to Mg++, together with an unknown concentration step resulting from binding to cell components other than the chromosome. PMID- 1938684 TI - Ionic binding, adaptive resistance and post-antibiotic effect of netilmicin and ciprofloxacin. AB - Ionic binding, post-antibiotic effect (PAE) and adaptive resistance to netilmicin and ciprofloxacin were investigated in 11 distinct clinical isolates. Both netilmicin and ciprofloxacin showed concentration dependent kill and PAE when bacteria were exposed to these antibiotics at 37 degrees C. The effects of netilmicin were maintained at 4 degrees C, when there is no energy dependent cell uptake of antibiotic, but were partially inhibited by exposure to NaCl and EDTA although not by Ca++. This supports the concept that ionic binding to the bacterial cell wall is important in the initial uptake of netilmicin. Ciprofloxacin showed no such effects at 4 degrees C. Adaptive resistance (reduced bacterial kill on second exposure) occurred with both netilmicin and ciprofloxacin but was seen more frequently with netilmicin. It persisted longer than classical PAE but, even after continuous exposure, was not enough to suggest a loss of kill with a twice daily dosing regimen of netilmicin or ciprofloxacin. PMID- 1938685 TI - Activity of clavulanate combinations against TEM-1 beta-lactamase-producing Escherichia coli isolates obtained in 1982 and 1989. AB - Recent reports of decreased susceptibility to amoxycillin/clavulanate and ticarcillin/clavulanate combinations amongst Escherichia coli isolates have been attributed to an increased frequency of hyperproduction of TEM-1 beta-lactamase. To test this claim we compared the activities of clavulanate combinations against consecutive E. coli isolates producing TEM-1 beta-lactamase that were obtained from clinical material at The London Hospital during 1982 (n = 50) and 1989 (n = 46). Enzyme production was quantified and related to the level of clavulanate required to potentiate amoxycillin and ticarcillin. The levels of TEM-1 enzyme production varied 150-fold amongst the isolates, partly because of variation in the gene copy number. A clear correlation existed between enzyme quantity and levels of resistance to the clavulanate combinations. However, there was no significant difference (P greater than 0.05, Mann-Whitney U test) between the isolates obtained in 1982 and 1989 in terms of the clavulanate concentrations required to potentiate the penicillins, or in the distribution of beta-lactamase activities present. PMID- 1938686 TI - Synergy with cefsulodin or piperacillin and three aminoglycosides or aztreonam against aminoglycoside resistant strains of Pseudomonas aeruginosa. AB - Fifty-one strains of Pseudomonas aeruginosa, with resistance to one or more amino glycosides, were tested for synergy with cefsulodin or piperacillin plus amikacin, tobramycin, gentamicin or aztreonam by the agar dilution technique. Cefsulodin plus any one of the three aminoglycosides regardless of the degree of resistance to the aminoglycoside was synergistic against P. aeruginosa for two thirds of the isolates. In contrast, synergy rates with piperacillin were much less uniform. The highest rate of synergy with piperacillin (90.0%) was observed with gentamicin for the gentamicin resistant strains. The lowest rate of synergy was observed with piperacillin plus amikacin (32.2%) for isolates with moderate resistance to amikacin. Synergy for strains with moderate resistance to amikacin was observed more commonly with cefsulodin than with piperacillin. Synergy for strains with a known mechanism of resistance to amikacin was more common with cefsulodin regardless of the mechanism of resistance. Cefsulodin or piperacillin in combination with aztreonam was rarely synergistic (less than 12%). PMID- 1938687 TI - In-vitro activity of imipenem combined with beta-lactam antibiotics for methicillin-resistant Staphylococcus aureus. AB - The in-vitro activity of imipenem combined with beta-lactam antibiotics was studied for 25 strains of methicillin and imipenem-resistant Staphylococcus aureus (MRSA) in comparison with that of fosfomycin combined with cefmetazole. Using the chequerboard agar dilution method, strong synergy was seen for all strains for imipenem with cefoperazone, cefotiam, cefpiramide or piperacillin. All fractional inhibitory concentration indices (FIC indices) of these combinations were less than or equal to 0.12. For the combination of imipenem with cefotiam the synergy was found to be bactericidal, but was not affected by the temperature of incubation, the concentration of sodium chloride in the medium or beta-lactamase production. However, for the combination of fosfomycin with cefmetazole only 44% of the strains with a mean FIC index of 0.55, showed synergy. The remaining 56% of strains showed either partial synergy (44%) or additive activity (12%). The combinations of imipenem with the beta-lactam antibiotics were more effective than that of fosfomycin with cefmetazole. PMID- 1938688 TI - Synergistic killing of gram-negative bacilli by cefotaxime, its desacetyl metabolite and human polymorphonuclear neutrophils. AB - Using an in-vitro model the effects of sub-MIC cefotaxime and its desacetyl metabolite singly and in combination on killing of E. coli by PMNs were studied. Our purpose was to determine if the parent compound and its metabolite had a synergistic effect on killing of E. coli by PMNs. Thymidine-labelled serum resistant Escherichia coli 018:K1:H7 were incubated during log phase growth with varying sub-MICs (1/2, 1/8, 1/32) of cefotaxime, its desacetyl metabolite and both agents together, or phosphate buffered saline (PBS) as a control for 90 min at 37 degrees C. The bacteria were then washed and a series of opsonization experiments was performed using intact and sonicated PMNs. Killing of bacteria was determined at 3, 10 and 20 min. Uptake and killing of bacteria by PMNs were measured using standard techniques. Pre-treatment of E. coli with cefotaxime alone and desacetyl cefotaxime and cefotaxime together resulted in significantly enhanced bacterial killing by PMNs at all three exposure times to PMNs. Pre treatment of the bacteria with sub-MICs of desacetyl cefotaxime alone showed enhanced killing only after exposure for three minutes. In all cases, any increased killing was independent of ingestion by the phagocytes. The opsonization experiments demonstrated that contact between bacteria and PMNs was necessary for optimal killing to occur. The enhanced killing of the sub-MIC antibiotic pre-treated bacteria was seen even when sonicated PMNs were used. The extent of bacterial killing, however, was less than that seen with intact PMNs. PMID- 1938689 TI - Factors affecting duration of in-vivo postantibiotic effect for aminoglycosides against gram-negative bacilli. AB - A murine thigh-infection model was used to determine the effect of certain host- and drug-related factors on the duration of the in-vivo postantibiotic effect (PAE) observed with aminoglycosides against Gram-negative bacilli. The role of neutrophils (PMNs), pharmacokinetics and variation among species and strains were studied. PAEs were quantitated after a single injection of gentamicin or amikacin. PAEs were several hours longer in normal mice than in neutropenic mice, in mice with renal impairment than in those with normal renal function, and with strains of Klebsiella pneumoniae than with strains of Escherichia coli, Serratia marcescens and Enterobacter cloacae. Among the 15 strains of Enterobacteriaceae studied, the duration of the in-vivo PAE did not correlate with MIC, duration of in-vitro PAE, and extent of in-vivo bactericidal activity. We conclude that prolonged PAEs are consistently observed in vivo with aminoglycosides against Enterobacteriaceae, and that this duration is enhanced in the presence of PMNs and by pharmacokinetic properties simulating those observed in humans. PMID- 1938690 TI - Plasma pharmacokinetics and tissue penetration of a novel antifungal triazole, Bay R 3783, and its long-lasting active metabolite, Bay U 3625, in rabbits. AB - The plasma pharmacokinetics and tissue penetration of Bay R 3783 (BR), a new antifungal triazole, and one of its active metabolites, Bay U 3625 (BU), were studied in rabbits. Plasma levels of BR and BU were determined simultaneously in five rabbits for six days after a single oral dose of 20 or 40 mg/kg BR. For BR, the mean Cmax was 1.9 +/- 0.4 mg/l, the Tmax 2.0 +/- 0.7 h, the AUC alpha 7.5 +/- 1.6 mg.h/l, and the terminal plasma T1/2 2.1 +/- 0.1 h. For BU, the mean Cmax was 0.84 +/- 0.09 mg/l, the Tmax 24 +/- 4 h, the AUC alpha 61.9 +/- 6.5 mg.h/l, and the plasma T1/2 was 48 +/- 3 h. In a multi-dose study, the plasma BR clearance during wash-out gradually diminished, suggesting possible metabolite inhibition of BRs biotransformation. No hepatic or renal toxicity was seen after 28 days of dosing with BR 40 mg/kg/d. Both BR and BU penetrated well into tissues, with tissue drug concentrations over three times higher than in plasma at multiple tissue sites. Persistence of BU in plasma, however, resulted in prolonged, higher tissue levels of BU than of BR. We conclude that BR is converted to a long lasting active metabolite BU, that persistence of BU in tissue is prolonged, and that these properties may permit BU to contribute significantly to the antifungal activity of BR. PMID- 1938691 TI - Nephrotoxicity in bone marrow transplant recipients receiving aminoglycoside plus cyclosporine or aminoglycoside alone. AB - We performed a retrospective analysis of the medical records of allogeneic bone marrow transplantation (BMT) patients receiving cyclosporine plus an aminoglycoside and autologous BMT patients receiving an aminoglycoside without concurrent cyclosporine in the immediate post-transplant period. Acute nephrotoxicity was not seen in any of the patients. Concomitantly used agents such as acyclovir, vancomycin and amphotericin did not worsen renal function. The present study suggests that aminoglycosides, if carefully monitored, can be safely combined with continuous infusion of cyclosporine without excessive nephrotoxicity. PMID- 1938692 TI - Treatment failure and recurrent human listeriosis. AB - We review 12 patients and report an additional two new patients, each of whom had two episodes of listeriosis. In seven patients the two episodes were due to the same strain of Listeria monocytogenes, and we speculate that this was a reactivation of the original infection. In one patient, isolates of L. monocytogenes from the two episodes differed, suggesting a chance reinfection. Twelve of the patients in this series received inappropriate therapy. Ampicillin plus an aminoglycoside for three to four weeks remain the treatment of choice. PMID- 1938693 TI - Out of the test tube into the frying pan: post-growth, pre-test variables. PMID- 1938694 TI - Phenotypic variability and sensitivity tests: carry on regardless. PMID- 1938695 TI - Calculating MIC50. PMID- 1938696 TI - The relationship between the 39 kb tetracycline-resistance plasmid and the 36 kb conjugative plasmid of Neisseria gonorrhoeae. PMID- 1938697 TI - Problems with Iso-Sensitest agar. PMID- 1938698 TI - Determination of Pseudomonas aeruginosa susceptibility to aminoglycosides using API and Autobac semi-automated systems. PMID- 1938699 TI - Interpretive criteria for antimicrobial susceptibility tests with cefodizime discs. PMID- 1938700 TI - Susceptibility of Enterococcus faecium to ampicillin. PMID- 1938701 TI - Necessity of a loading dose when using vancomycin in critical-ill patients. PMID- 1938702 TI - Opportunistic and pathogenic fungi. AB - The number of fungal species reported to cause disease in man is increasing rapidly. Very few of these fungi are capable of infecting a normal host. Important progress has been achieved in an understanding of fungal pathogenicity including the mechanisms of adherence to host tissues, penetration of tissues, multiplication within the host, and the interaction of fungal cells with host effector cells. In addition to the increase in infections by opportunistic and pathogenic fungi in compromised patients, caused by Candida spp., Aspergillus spp., Cryptococcus neoformans, Histoplasma capsulatum and Coccidioides immitis, many fungi that occur as saprophytes in the environment and which had previously been considered to be nonpathogenic are now being encountered as causes of human infection. The advent of these unusual infections has led to reappraisal of the diagnostic tests involved in the investigation of fungal infections and has had important implications for the choice of treatment. Many of these fungi have a similar tissue appearance and the organisms must be isolated and identified to ensure that the most appropriate treatment is given. PMID- 1938703 TI - The clinical presentation and diagnosis of invasive fungal infections. AB - The frequency of invasive fungal infections is increasing owing to the increasing numbers and improved survival of immuno-compromised patients. The fungi responsible for these infections are predominantly opportunistic pathogens. The clinical features and diagnosis of the four commonest infections (invasive candidosis and aspergillosis, cryptococcosis and mucormycosis) are discussed. Particular emphasis is given to the identification of risk factors for these infections, which are different for each disease. As these organisms are common contaminants or commensals, definitive diagnosis requires culture from sites that are normally sterile or histological demonstration of tissue invasion. Definitive diagnosis is not always possible, in part owing to the severe nature of patients' underlying illnesses. A high proportion of cases are diagnosed post mortem because of difficulties in establishing a diagnosis. Clinical diagnoses thus need to be made early in the course of these infections, but a high index of suspicion and knowledge of the clinical manifestations are required. PMID- 1938704 TI - Developments in the serological diagnosis of opportunistic fungal infections. AB - Recent years have seen some progress in the design of serodiagnostic tests for the medically important invasive mycoses. This has included the introduction of latex agglutination tests for antigen detection in systemic candidosis and invasive aspergillosis. The circulating cytoplasmic antigens of Candida albicans and Aspergillus fumigatus have recently been delineated as heat-shock proteins of approximate molecular weight 90 KD. PMID- 1938705 TI - Antifungal therapy and the new azole compounds. AB - At present there are weaknesses in the range and scope of antifungal chemotherapy. The development of a new group of azole drugs, the triazoles, has introduced antifungal agents with broad-spectrum activity which can be given by the oral route. Fluconazole is very well absorbed and has good penetration. While its principal activity is against yeasts and there are clinical data to support its use in candida and cryptococcus infections, little work has been completed on its clinical use in aspergillosis. Itraconazole is less well absorbed, but highly bound in tissue. Its spectrum of activity is somewhat broader than that of fluconazole and it is clinically active against superficial mycoses and some of the infections caused by pathogenic fungi such as Histoplasma capsulatum. There is some early evidence of efficacy in aspergillosis but more studies are required in neutropenic patients. Both drugs show promise but comparative assessments are sorely needed. PMID- 1938706 TI - Developments in the management of superficial fungal infections. AB - In the common superficial mycoses, caused by the dermatophytes and by Candida spp., the established agents, amphotericin B and griseofulvin (themselves important advances over the previously available simple topical preparations) have been limited in effectiveness in some situations. The introduction of the azole group of drugs, with a broad spectrum of activity and availability in varied preparations, has diversified the treatment possibilities in dermatophytoses and candidosis, and also in pityriasis versicolor and related conditions. Two other introductions appear promising: terbinafine has been very effective in early trials in dermatophytoses, and amorolfine may have a particular role in isolated nail infection, whether caused by dermatophytes or by less common fungi. PMID- 1938707 TI - Vulvovaginal candidosis. AB - Vulvovaginal candidosis is increasing in incidence in many developed countries. Although for many women the sporadic occurrence of symptomatic episodes causes no more than temporary inconvenience and discomfort, in others the chronic or recurrent pattern of symptoms can be very distressing and disabling. Knowledge of the pathogenesis, predisposing factors and clinical features, although still incomplete, permits improved individual patient management and more appropriate use of specific antifungal therapy. Topical treatment with either polyenes or imidazoles gives short term mycological cure rates greater than 90%, but subsequent recolonization of the vagina and symptomatic relapse is common. Azole drugs offer the possibility of oral treatment which has increased patient acceptability; in particular, fluconazole, in a single dosage of 150 mg, is effective, well tolerated and safe. In chronic or recurrent disease, when underlying and predisposing conditions have been excluded, intermittent prophylaxis (topical or oral) may reduce the frequency of acute symptomatic episodes. PMID- 1938708 TI - Clinical management of fungal infection in patients with AIDS. AB - The frequency of disseminated fungal infection in patients with the Acquired Immune Deficiency Syndrome (AIDS) has provided a major impetus for the reevaluation of standard antifungal protocols as well as accelerating the development and clinical testing of new agents. As a result, useful clinical guidelines regarding the use of amphotericin B and flucytosine in cryptococcosis are beginning to emerge that relate specifically to patients with AIDS. Oral agents, most notably fluconazole have shown promise and are now being evaluated in controlled clinical trials. Histoplasmosis and coccidioidomycosis have emerged as significant infections and pose new problems in both diagnosis and management. Although amphotericin B and flucytosine must still be used for induction therapy in patients with these infections, preliminary studies of itraconazole suggest that it could be useful for maintenance therapy. Despite there being considerably less clinical experience with histoplasmosis and coccidioidomycosis than with cryptococcosis, it is hoped that the lessons learnt with cryptococcosis will accelerate the development of new diagnostic assays and improved therapeutic approaches. PMID- 1938709 TI - Fungal infections in drug users. AB - Fungal infections may account for 5-50% of serious infections in intravenous drug users, and for 5-50 per 100,000 hospital admissions. The fungi most commonly encountered are Candida and Aspergillus spp. Candidosis may be disseminated, with lesions in superficial structures, the eye and the skeletal system, or limited to the eye, the heart (as endocarditis) or the central nervous system. Aspergillosis usually presents as endophthalmitis or as central nervous system infection. Mucormycosis is also met with occasionally, and various fungi may cause endophthalmitis or endocarditis. Antifungal therapy for intravenous drug use related infections is no different from that for similar mycoses in other patients, but the management of intravenous drug users requires considerable clinical skill. PMID- 1938710 TI - The prophylaxis of fungal infections. AB - With the increase in use of immunosuppressive therapies, solid organ and bone marrow transplantation and the recognition of the acquired immune deficiency syndrome (AIDS) an increased incidence and awareness of fungal infection has occurred in almost all disciplines of medicine. The problem of being unable to identify such infections accurately before serious morbidity or mortality occurs indicates a continued need for a prophylactic approach to these infections. Fortunately, the development of new, safer antifungal agents appears to be occurring. Novel approaches with amphotericin B and the use of bone marrow growth factors merit attention. Specific recommendations for antifungal prophylaxis depend on a number of factors pertinent to the individual treatment centre. PMID- 1938711 TI - Pleural liquid pressure. AB - The knowledge of pleural liquid pressure (Pliq) is essential for understanding the mechanical coupling between lung and chest wall and the liquid exchanges of the pleural space. In the last decade, research in this field contributed new ideas and stimulating controversies but also caused some confusion. These aspects, along with the older contributions, are considered in this review, which is divided into three sections. The topics of the first section are 1) measurements of Pliq with different techniques in various mammals and various regions of the pleural space, 2) comparison of Pliq with the pressure exerted by the lung recoil (Ppl), and 3) vertical gradient of Pliq and downward flow of pleural liquid. In the second section the mechanisms absorbing liquid from the pleural space are analyzed: 1) Starling forces of the visceral pleura, 2) lymphatic drainage through the stomata of the parietal pleura, and 3) active transport of solutes. The third section deals with 1) measurements of pleural liquid thickness with two approaches in the costal region of various mammals and 2) mechanisms preventing a complete removal of pleural liquid and, thus, ensuring the lubrication. PMID- 1938712 TI - Vascular resistance and Kf in normal and PMA-injured rabbit lungs: effects of adenosine. AB - The effects of adenosine (ADO) on pulmonary vascular resistance (PVR) distribution, vascular compliance (C), and permeability were determined in normal and PMA-injured isolated rabbit lungs perfused with a 1:1 mixture of 6% albumin in Krebs-Henseleit buffer and autologous blood. ADO or vehicle was continuously infused into the reservoir at 1,4, or 5 mumol/min after a 1-mumol bolus of ADO or vehicle. The capillary filtration coefficient (Kf) and arterial, venous, and double occlusion pressures were measured at baseline and 30 min after phorbol myristate acetate (PMA; 4 x 10(-8) M) or vehicle. Perfusate differential and total leukocyte counts as well as adenine nucleotides, 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TxB2) concentrations were determined at each measurement period. ADO was recovered as hypoxanthine and inosine in the perfusate. ADO alone did not alter PVR, C, Kf, or TxB2 but reduced 6-keto-PGF1 alpha levels. PMA induced an increase in Kf (0.024 +/- 0.002 to 0.040 +/- 0.006 g.cmH2O-1.min-1, P less than 0.05) that was completely blocked by 4 or 5 mumol/min ADO. PVR increased by 63 +/- 11% after PMA, primarily in the arteries and arterial and venous microvessels. The postcapillary resistance increase was blunted by 4 mumol/min ADO; 5 mumol/min ADO prevented the PVR increase in all segments. ADO did not affect the initial adherence of neutrophils in the lung or the PMA-induced 87 +/- 2% decrease in circulating leukocytes (greater than 98% lymphocytes) or threefold increase in TxB2 levels. These results suggest that protection by ADO is not mediated by the altering of cyclooxygenase products or by leukocyte adherence. PMID- 1938713 TI - Response of slowly adapting pulmonary stretch receptors to reduced lung compliance. AB - We examined the steady-state response of slowly adapting pulmonary stretch receptors (SAPSRs) to reduced lung compliance in open-chest cats with lungs ventilated at eupneic rate and tidal volume (VT) and with a positive end expiratory pressure (PEEP) of 3-4 cmH2O. Transient removal of PEEP decreased compliance by approximately 30% and increased transpulmonary pressure (Ptp) by 1 2.5 cmH2O. Reduction of compliance significantly decreased SAPSR discharge in deflation and caused a small increase in discharge at the peak of inflation; it had little effect on discharge averaged over the ventilatory cycle. Increasing VT to produce a comparable increase in Ptp significantly increased peak discharge. Thus unlike rapidly adapting receptors, whose discharge is increased more effectively by reduced compliance than by increased VT, SAPSRs are stimulated by increased VT but not by reduced compliance. We speculate that the most consistent effect of reduced compliance on SAPSRs (the decrease in deflation discharge) was due to the decreased time constant for deflation in the stiffer lung. This alteration in firing may contribute to the tachypnea evoked as the lungs become stiffer. PMID- 1938714 TI - Effects of pyridostigmine bromide on human thermoregulation during cold water immersion. AB - This study examined the effects of an oral 30-mg dose of pyridostigmine bromide (PYR) on thermoregulatory and physiological responses of men undergoing cold stress. Six men were immersed in cold water (20 degrees C) for up to 180 min on two occasions, once each 2 h after ingestion of PYR and 2 h after ingestion of a placebo. With PRY, erythrocyte cholinesterase inhibition was 33 +/- 12% (SD) 110 min postingestion (10 min preimmersion) and 30 +/- 7% at termination of exposure (mean 117 min). Percent cholinesterase inhibition was significantly related to lean body mass (r = -0.91, P less than 0.01). Abdominal discomfort caused termination in three of six PYR experiments but in none of the control experiments (mean exposure time 142 min). During immersion, metabolic rate, ventilatory volume, and respiratory rate increased significantly (P less than 0.05) over preimmersion levels and metabolic rate increased with duration of immersion (P less than 0.01) in both treatment but did not differ between conditions. PYR had no significant effect on rectal temperature, mean body temperature, thermal sensations, heart rate, plasma cortisol, or change in plasma volume. It was concluded that a 30-mg dose of PYR does not increase an individual's susceptibility to hypothermia during cold water immersion; however, in combination with cold stress, PYR may result in marked abdominal cramping and limit cold tolerance. PMID- 1938715 TI - Effect of triiodothyronine-induced thyrotoxicosis on airway hyperresponsiveness. AB - To determine whether thyrotoxicosis has an effect on the asthmatic state in subjects with mild asthma, airway responsiveness, lung function, and exercise capacity were measured in a randomized double-blind placebo-controlled trial before and after liothyronine (triiodothyronine, T3)-induced thyrotoxicosis. Baseline evaluation of 15 subjects with mild asthma included clinical evaluation, thyroid and routine pulmonary function tests, airway responsiveness assessment by methacholine inhalation challenge, and a symptom-limited maximal exercise test. For all subjects, the initial testing revealed that the dose of methacholine which provoked a 20% fall in forced expiratory volume in 1s (PD20) was in a range consistent with symptomatic asthma. There was no significant change in pulmonary function tests, airway reactivity (PD20), or exercise capacity in either the placebo or the T3-treated groups. Thyroid function tests confirmed mild sustained thyrotoxicosis in the T3-treated groups. We conclude that mild T3-induced thyrotoxicosis of 4-wk duration had no effect on lung function, airway responsiveness, or exercise capacity in subjects with mild asthma. PMID- 1938716 TI - Factors controlling fat mobilization from human subcutaneous adipose tissue during exercise. AB - To investigate possible factors that limit fat utilization during exercise, arteriovenous differences of plasma nonesterified fatty acids (NEFA) and glycerol were measured across the subcutaneous adipose tissue of the anterior abdominal wall in nine subjects who exercised for 60 min at 50-70% of their maximal O2 consumption. The large gradient of NEFA concentration from adipose tissue venous to arterial plasma increased throughout the exercise period. Maximal plasma NEFA concentrations in adipose venous drainage were reached postexercise (median 3,800 mumol/l), with a median NEFA-to-albumin molar ratio of 5.7. Fractional reesterification of fatty acids within the tissue (assessed from the ratio of NEFA to glycerol release) was 20-30% in the basal state and declined during exercise. After exercise there was apparently negative reesterification, implying release of NEFA retained in adipose tissue during exercise. Although these findings challenge current views on the regulation of NEFA release, they are in agreement with the concept of supply of fatty acids from adipose tissue as the major factor limiting fat oxidation during sustained exercise. PMID- 1938717 TI - Short-term effect of tidal pleural pressure swings on pulmonary blood flow during rest and exercise. AB - Because pleural pressure (Ppl) has important effects on venous return and left ventricular function, it is possible that the magnitude of respiratory fluctuations in Ppl importantly influences cardiac output (pulmonary blood flow, QL) during exercise. To examine this question, we increased (+15 cmH2O) and decreased (-11 cmH2O) the amplitude of fluctuations in Ppl by elastic loading and unloading, respectively, during steady-state exercise (50 W) and estimated the corresponding changes in QL from measurement of breath-by-breath alveolar O2 consumption [(Vo2)A] by a modification of the technique of Beaver et al. (J. Appl. Physiol. 51: 1662-1675, 1981). Load changes were applied for three breaths. Using oscilloscopic volume feedback, subjects maintained constant breathing pattern and end-expiratory volume during control and experimental breaths. This procedure minimized errors in computing (Vo2)A. Furthermore, because over the brief period of load change (especially the first 1 or 2 breaths) mixed venous and arterial O2 contents were not likely to have changed, changes in (Vo2)A reflected changes in QL according to the Fick principle. In six normal subjects, neither loading nor unloading had any effect on (Vo2)A in the first, second, or third breath (P greater than 0.5). Additional studies at rest produced equally negative results. We conclude that the magnitude of respiratory fluctuations in Ppl has no short-term effect on pulmonary blood flow at rest or during mild exercise. PMID- 1938718 TI - Persistence of the Hering-Breuer reflex beyond the neonatal period. AB - There is conflicting evidence regarding the persistence of the Hering-Breuer reflex (HBR) beyond the 1st wk of life. This study was designed to assess the influence of postnatal age on the HBR. The airway occlusion technique was used to assess changes in respiratory timing during stimulation of the HBR in healthy full-term unsedated infants measured shortly after birth and at 6-8 wk of life. The strength of the HBR was assessed from the relative change in expiratory time (TE) after end-inspiratory occlusion compared with resting TE during spontaneous breathing. Paired studies were performed in 31 infants at approximately 2 days and 6 wk of age. There was a significant increase in TE during each occlusion in every infant irrespective of age at measurement. No maturational changes were observed. The increase in TE after end-inspiratory occlusion was 91.9 +/- 31.6% (SD) (range 38-158%) at approximately 2 days and 89.8 +/- 30.7% (range 44-175%) at approximately 6 wk. We conclude that the activity of the HBR during tidal breathing persists beyond the neonatal period and that there is no statistically significant change in its strength during the first 2 mo life in healthy infants during natural sleep. PMID- 1938719 TI - Plasma protein osmotic pressure equations and nomogram for sheep. AB - The equations developed by Landis and Pappenheimer (Handbook of Physiology. Circulation, 1963, p. 961-1034) for calculating the protein osmotic pressure of human plasma proteins have been frequently used for other animal species without regard to the fractional albumin concentration or correction for protein-protein interaction. Using an electronic osmometer, we remeasured the protein osmotic pressure of purified sheep albumin and sheep plasma partially depleted of albumin. We measured protein osmotic pressures of serial dilutions over the concentration range 0-180 g/l for albumin and 0-100 g/l for the albumin-depleted proteins at room temperature (26 degrees C). Using a nonlinear least squares parameter-fitting computer program, we obtained the equation of best fit for purified albumin, and then we used that equation together with the measured albumin fraction to obtain the best-fit equation for the nonalbumin proteins. The equation for albumin is IIcmH2O,39 degrees C = 0.382C + 0.0028C2 + 0.000013C3, where C is albumin concentration in g/l. The equation for the nonalbumin fraction is IIcmH2O,39 degrees C = 0.119C + 0.0016C2. Up to 200- and 100-g/l protein concentration, respectively, these equations give the least standard error of the estimate for each of the virial coefficients. The computed number-average molecular weight for the nonalbumin proteins is 222,000. Using the new equations, we constructed a nomogram, based on the one of Nitta and co-workers (Tohoku J. Exp. Med. 135: 43-49, 1981). We tested the nomogram using 144 random samples of sheep plasma and lymph from 31 sheep. We obtained a correlation coefficient of 0.99 between the measured and nomogram estimates of protein osmotic pressure. PMID- 1938720 TI - Changes in upper airway muscle activation and ventilation during phasic REM sleep in normal men. AB - Several investigators have observed that irregular breathing occurs during rapid eye-movement (REM) sleep in healthy subjects, with ventilatory suppression being prominent during active eye movements [phasic REM (PREM) sleep] as opposed to tonic REM (TREM) sleep, when ocular activity is absent and ventilation more regular. Inasmuch as considerable data suggest that rapid eye movements are a manifestation of sleep-induced neural events that may importantly influence respiratory neurons, we hypothesized that upper airway dilator muscle activation may also be suppressed during periods of active eye movements in REM sleep. We studied six normal men during single nocturnal sleep studies. Standard sleep staging parameters, ventilation, and genioglossus and alae nasi electromyograms (EMG) were continuously recorded during the study. There were no significant differences in minute ventilation, tidal volume, or any index of genioglossus or alae nasi EMG amplitude between non-REM (NREM) and REM sleep, when REM was analyzed as a single sleep stage. Each breath during REM sleep was scored as "phasic" or "tonic," depending on its proximity to REM deflections on the electrooculogram. Comparison of all three sleep states (NREM, PREM, and TREM) revealed that peak inspiratory genioglossus and alae nasi EMG activities were significantly decreased during PREM sleep compared with TREM sleep [genioglossus (arbitrary units): NREM 49 +/- 12 (mean +/- SE), TREM 49 +/- 5, PREM 20 +/- 5 (P less than 0.05, PREM different from TREM and NREM); alae nasi: NREM 16 +/- 4, TREM 38 +/- 7, PREM 10 +/- 4 (P less than 0.05, PREM different from TREM)]. We also observed, as have others, that ventilation, tidal volume, and mean inspiratory airflow were significantly decreased and respiratory frequency was increased during PREM sleep compared with both TREM and NREM sleep. We conclude that hypoventilation occurs in concert with reduced upper airway dilator muscle activation during PREM sleep by mechanisms that remain to be established. PMID- 1938721 TI - Effects of volume history and vagotomy on pulmonary and chest wall mechanics in cats. AB - Using the technique of rapid airway occlusion during constant-flow inflation, we studied the effects of inflation volume, different baseline tidal volumes (10, 20, and 30 ml/kg), and vagotomy on the resistive and elastic properties of the lungs and chest wall in six anesthetized tracheotomized paralyzed mechanically ventilated cats. Before vagotomy, airway resistance decreased significantly with increasing inflation volume at all baseline tidal volumes. At any given inflation volume, airway resistance decreased with increasing baseline tidal volume. After vagotomy, airway resistance decreased markedly and was no longer affected by baseline tidal volume. Prevagotomy, pulmonary tissue resistance increased progressively with increasing lung volume and was not affected by baseline tidal volume. Pulmonary tissue resistance decreased postvagotomy. Chest wall tissue resistance increased during lung inflation but was not affected by either baseline tidal volume or vagotomy. The static volume-pressure relationships of the lungs and chest wall were not affected by either baseline tidal volume or vagotomy. The data were interpreted in terms of a linear viscoelastic model of the respiratory system (J. Appl. Physiol. 67: 2276-2285, 1989). PMID- 1938722 TI - Hypobaric hypoxia (380 Torr) decreases intracellular and total body water in goats. AB - The effects of prolonged hypoxia on body water distribution was studied in four unanesthetized adult goats (Capra lircus) at sea level and after 16 days in a hypobaric chamber [(380 Torr, 5,500 m, 24 +/- 1 degrees C); arterial PO2 = 27 +/- 2 (SE) Torr]. Total body water (TBW), extracellular fluid volume (ECF), and plasma volume (PV) were determined with 3H2O, [14C]inulin, and indocyanine green dye, respectively. Blood volume (BV) [BV = 100PV/(100 - hematocrit)], erythrocyte volume (RCV) (RCV = BV - PV), and intracellular fluid (ICF) (ICF = TBW - ECF) and interstitial fluid (ISF) (ISF = ECF - PV) volumes were calculated. Hypoxia resulted in increased pulmonary ventilation and arterial pH and decreased arterial PCO2 and PO2 (P less than 0.05). In addition, body mass (-7.1%), TBW ( 9.1%), and ICF volume (-14.4%) all decreased, whereas ECF (+11.7%) and ISF (+27.7%) volumes increased (P less than 0.05). The decrease in TBW accounted for 89% of the loss of body mass. Although PV decreased significantly (-15.3%), BV was unchanged because of an offsetting increase in RCV (+39.5%; P less than 0.05). We conclude that, in adult goats, prolonged hypobaric hypoxia results in decreases in TBW volume, ICF volume, and PV, with concomitant increases in ECF and ISF volumes. PMID- 1938723 TI - Net lactate uptake during progressive steady-level contractions in canine skeletal muscle. AB - The purpose of this study was to determine the changes in net lactate uptake (L) by skeletal muscle with a constant elevated blood lactate concentration during steady-level contractions of increasing intensity. The gastrocnemius-plantaris muscle group was isolated in situ in 11 anesthetized dogs. An infusion of lactate/lactic acid at a pH of 3.5-3.7 established a blood lactate concentration of approximately 9 mM while maintaining normal blood gas/pH status. L was measured during three consecutive 30-min periods during which the muscles 1) rested, 2) contracted at 1 Hz, and 3) contracted at 4 Hz. L was always positive, indicating net uptake throughout the lactate/lactic acid infusion. Steady-level O2 uptake averaged 10.9 +/- 2.2 ml.kg-1.min-1 (0.49 +/- 0.10 mmol.kg-1.min-1) at rest, 39.3 +/- 2.1 (1.75 +/- 0.09) at 1 Hz, and 127.8 +/- 9.2 (5.70 +/- 0.41) at 4 Hz. Steady-level L increased with the metabolic rate from 0.113 +/- 0.058 mmol.kg-1.min-1 at rest to 0.329 +/- 0.026 at 1 Hz and 0.715 +/- 0.108 at 4 Hz. The increase in L from rest to 1 Hz was accomplished mainly by an increase in arteriovenous lactate difference, whereas the increase from 1 to 4 Hz was entirely due to a large increase in blood flow. These results support the idea that skeletal muscle is not simply a producer of lactate but can be a significant consumer of lactate even during contractions with a large elevation in metabolic rate. PMID- 1938724 TI - Effects of invariant sympathetic activity on cutaneous circulatory responses to heat stress. AB - This study investigated the role of sympathetic withdrawal on blood flow responses in cutaneous arteriovenous anastomoses (AVAs) and capillaries to direct and indirect heat stress. This was achieved by clamping sympathetic activity (SC) to the tail of anesthetized rats so that constrictor tone remained invariant during exposure of either the animal's tail (direct heating) or body (indirect heating) to a 35 degrees C environment. Flow through the AVAs in the tail was evaluated by laser-Doppler flowmetry (LDF), while capillary flow was investigated by videodensitometry measurements of blood cell velocity (CBV) in single capillaries within the subepidermal vascular plexus. Both direct and indirect heating significantly increased LDF and CBV. In comparison to blood flow responses in sham-operated control rats, the SC procedure resulted in significantly lower LDF responses to both direct and indirect heat stress. By contrast, the response of CBV was not significantly affected by SC during either mode of heating. These results indicate that the withdrawal of sympathetic constrictor tone plays a role in the response of cutaneous AVAs, but not precapillary arterioles, to direct as well as indirect heat stress. Additional studies on unanesthetized animals showed that superimposing body heating on a base of local heating elicited a further increase in LDF, suggesting that local heating does not deplete neural mediated dilatory reserve. PMID- 1938725 TI - Activity of pulmonary surfactant after blocking the associated proteins SP-A and SP-B. AB - To investigate the role of the pulmonary surfactant-associated proteins SP-A and SP-B, the respective monoclonal antibody (anti-A or anti-B) was added to porcine pulmonary surfactant at a weight ratio of 1:2, and the mixtures were tested on surfactant-deficient immature newborn rabbits (gestational age 26 days). Under pentobarbital sodium anesthesia and mechanical ventilation with a 25-cmH2O peak insufflation pressure, the tidal volumes of the animals given surfactant alone and of those given surfactant containing anti-A were 27.9 +/- 5.1 and 25.1 +/- 9.6 (SD) ml/kg, respectively, whereas that of those given surfactant with anti-B was 5.8 +/- 3.6 ml/kg (P less than 0.05). The surface adsorption times of surfactant alone and of anti-A-containing surfactant were less than 0.8 s compared with greater than 120 s (P less than 0.01) for anti-B-containing surfactant. The anti-B suppressed the surfactant activity until the weight ratio was decreased to 2:100. The role of SP-A could not be clarified, but it was concluded that SP-B is an essential factor for surfactant activity. PMID- 1938726 TI - High pressure modifies respiratory activity in isolated rat brain stem-spinal cord. AB - Exposure to hyperbaric pressure causes a constellation of motor disturbances and ventilatory difficulties in animals and humans. The present experiments were designed to examine the effects of hyperbaric pressure on the rhythmic activity of the respiratory center in the absence of peripheral sensory afferents by using the isolated brain stem-spinal cord preparation from newborn rats. In addition, we examined the effect of pressure on the response of the respiratory center to sensory input from the trigeminal and vagus cranial nerves. Hyperbaric pressure significantly depressed the mean inspiratory drive (frequency X time integral of single electrical bursts) in C5 but not in C1 ventral roots. Pressure also reduced the amount of inhibition on the respiratory activity normally exerted by trigeminal and vagal nerve stimulation and in some cases reversed it to excitation. It is concluded that in the absence of sensory input, exposure to hyperbaric pressure depresses central respiratory activity. However, in an intact system, it may alter the balance between excitation and inhibition and render the system hyperexcitable to the same sensory input. PMID- 1938727 TI - Oronasal partitioning of ventilation during exercise in humans. AB - The partitioning of oronasal breathing was studied in five normal subjects during progressive exercise. Subjects performed three to five identical runs, each consisting of four 1-min work periods at increments of 50 W. Nasal and oral airflow were measured simultaneously using a partitioned face mask both during and for 4 min after exercise. Total mean flows were the sum of nasal and oral flows. At a total mean inspiratory flow of 2 l/s, the nasal fraction of total flow was 0.36 +/- 0.04 (SE) and decreased by 6 +/- 3% between total flows of 1.5 and 2.5 l/s. Throughout exercise, the nasal fraction of total mean inspiratory flow did not differ from that of total expiratory flow and was similar to that of total mean inspiratory flow during the postexercise period at a corresponding total mean flow (both P greater than 0.02). The results show that oronasal flow partitioning is not directly due to the exercise itself but is related to the level of ventilation and is uninfluenced by the direction of upper airway flow (i.e., inspiratory vs. expiratory). These findings suggest tightly controlled modulation of the relative resistances of the oral and/or nasal pathways. PMID- 1938729 TI - Rostrocaudal pattern of fiber-type changes in an overloaded rat ankle extensor. AB - Our aim was to quantify the overload-induced hypertrophy and conversion of fiber types (type II to I) occurring in the medial head of the gastrocnemius muscle (MG). Overload of MG was induced by a bilateral tenotomy/retraction of synergists, followed by 12-18 wk of regular treadmill locomotion (2 h of walking/running per day on 3 of 4 days). We counted all type I fibers and determined type I and II mean fiber areas in eight equidistant sections taken along the length of control and overloaded MG. Increase in muscle weights (31%), as well as in total muscle cross-sectional areas (37%) and fiber areas (type I, 57%; type II, 34%), attested to a significant hypertrophic response in overloaded MG. An increase in type I fiber composition of MG from 7.0 to 11.5% occurred as a result of overload, with the greatest and only statistically significant changes (approximately 70-100%) being found in sections taken from the most rostral 45% of the muscle length. Results of analysis of sections taken from the largest muscle girth showed that it significantly underestimated the extent of fiber conversion that occurred throughout the muscle as a whole. These data obtained on the MG, which possesses a compartmentalization of fiber types, support the notion that all fiber types respond to this model with a similar degree of hypertrophy. Also, they emphasize the complex nature of the adaptive changes that occur in these types of muscles as a result of overload. PMID- 1938728 TI - Influence of active muscle mass on glucose homeostasis during exercise in humans. AB - To study the effect of increasing amounts of exercising muscle mass on the relationship between glucose mobilization and peripheral glucose uptake, seven young men (23-28 yr) bicycled for 70 min at a work load of 55-60% VO2max. From minute 30 to 50, arm cranking was added and total work load increased to 82 +/- 4% VO2max. During leg exercise, hepatic glucose production (Ra) increased in parallel with peripheral glucose uptake (Rd) and euglycemia was maintained. During arm + leg exercise, Ra increased more than Rd and accordingly plasma glucose increased from 5.11 +/- 0.22 to 8.00 +/- 0.66 mmol/l (P less than 0.05). Plasma catecholamines increased three- to four-fold more during arm + leg exercise than during leg exercise. Leg glucose uptake increased with time regardless of arm cranking. Net leg lactate release during leg exercise was reverted to a net leg lactate uptake during arm + leg exercise. The rate of glycogen breakdown in exercising leg muscle was not altered by addition of arm cranking. In conclusion, when large amounts of muscle mass are active, plasma catecholamines increase sharply and mobilization of glucose exceeds peripheral glucose uptake. This indicates that mechanisms other than feedback regulation to maintain euglycemia are involved in hormonal and substrate mobilization during intense exercise in humans. PMID- 1938730 TI - Relationships between abdominal and diaphragmatic volume displacements. AB - We investigated the relationship between the volumes displaced by the diaphragm and the abdominal wall during spontaneous breathing in supine anesthetized dogs. Diaphragmatic volume displacement (Vdi) was calculated from measurements taken from anteroposterior fluoroscopic images employing a previously described geometric model. The volume displacement of the abdominal wall (Vabd) was measured with a calibrated Respitrace. Shortening of single diaphragm muscle bundles in costal and crural regions was measured as the distance between radiopaque beads sutured to the peritoneal surface of the muscle. We found that Vdi always exceeded Vabd, but Vabd/Vdi was larger in animals in which the abdominal wall was more compliant. In this preparation, Vdi is better correlated with costal than with crural shortening. Vabd did not correlate with either costal or crural shortening. We infer that the difference between Vdi and Vabd reflects the volume displacement of the lower rib cage caused by diaphragm contraction. This volume difference was tightly correlated with costal shortening. We conclude from these data that coupling between Vdi and Vabd is influenced by the relative compliances of the chest wall and abdomen. Shortening of regions of the diaphragm may have variable relationships to the measured volume displacement, but costal shortening is intimately related to expansion of the lower rib cage. PMID- 1938731 TI - Regional distribution of blood flow within the diaphragm. AB - We investigated the regional distribution of blood flow (Q) within the costal and crural portions of the diaphragm in a total of eight anesthetized supine mongrel dogs. Q was measured with 15-microns microspheres, radiolabeled with three different isotopes, injected into the left ventricle during spontaneous breathing (SB), inspiratory resistive loading (IR), and mechanical ventilation after paralysis (P). At necropsy, the costal and crural portions of each hemidiaphragm were arbitrarily subdivided along a sagittal plane into five to seven and three sections, respectively. During P, there was a dorsoventral Q gradient within the costal part of the diaphragm. During SB there was a fourfold increase in the gradient of Q. Furthermore, during IR, in which mouth pressures of -16 +/- 4 cmH2O were generated, there was a further increase in the gradient of Q. During both SB and IR, Q to the most ventral portion of the costal diaphragm was 26 +/- 6% less than the peak value. In two dogs, studied prone and supine, there was no difference in the Q gradients between the two postures. Over the dorsal 80% of the costal diaphragm there was also a dorsoventral gradient of muscle thickness, such that the most dorsal part was 54 +/- 2% (n = 5) that of the ventral portion. In contrast, there was no consistent gradient of Q or muscle thickness within the crural diaphragm. Our results demonstrate a topographical gravity-independent distribution of Q in the costal, but not the crural, diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938732 TI - Heat loss from the human head during exercise. AB - Evaporative and convective heat loss from head skin and expired air were measured in four male subjects at rest and during incremental exercise at 5, 15, and 25 degrees C ambient temperature (Ta) to verify whether the head can function as a heat sink for selective brain cooling. The heat losses were measured with an open circuit method. At rest the heat loss from head skin and expired air decreased with increasing Ta from 69 +/- 5 and 37 +/- 18 (SE) W (5 degrees C) to 44 +/- 25 and 26 +/- 7 W (25 degrees C). At a work load of 150 W the heat loss tended to increase with increasing Ta: 119 +/- 21 (head skin) and 82 +/- 5 W (respiratory tract) at 5 degrees C Ta to 132 +/- 27 and 103 +/- 12 W at 25 degrees C Ta. Heat loss was always higher from the head surface than from the respiratory tract. The heat losses, separately and together (total), were highly correlated to the increasing esophageal temperature at 15 and 25 degrees C Ta. At 5 degrees C Ta on correlation occurred. The results showed that the heat loss from the head was larger than the heat brought to the brain by the arterial blood during hyperthermia, estimated to be 45 W per 1 degree C increase above normal temperature, plus the heat produced by the brain, estimated to be up to 20 W. The total heat to be lost is therefore approximately 65 W during a mild hyperthermia (+1 degrees C) if brain temperature is to remain constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938733 TI - Interactive effects of body posture and exercise training on maximal oxygen uptake. AB - To determine the effect of posture on maximal O2 uptake (VO2 max) and other cardiorespiratory adaptations to exercise training, 16 male subjects were trained using high-intensity interval and prolonged continuous cycling in either the supine or upright posture 40 min/day 4 days/wk for 8 wk and 7 male subjects served as non-training controls. VO2 max measured during upright cycling and supine cycling, respectively, increased significantly (P less than 0.05) by 16.1 +/- 3.4 and 22.9 +/- 3.4% in the supine training group (STG) and by 14.6 +/- 2.0 and 6.0 +/- 2.0% in the upright training group (UTG). The increase in VO2 max measured during supine cycling was significantly greater (P less than 0.05) in the STG than in the UTG. The increase in VO2 max in the UTG was significantly greater (P less than 0.05) when measured during upright exercise than during supine exercise. However, there was no significant difference in posture-specific VO2 max adaptations in the STG. A postural specificity was also evident in other maximal cardiorespiratory variables (ventilation, CO2 production, and respiratory exchange ratio). In the UTG, maximal heart rate decreased significantly (P less than 0.05) only during supine cycling; there was no significant difference in maximal heart rate after training in the STG. We conclude that posture affects maximal cardiorespiratory adaptations to cycle training. Additionally, supine training is more effective than upright training in increasing maximal cardiorespiratory responses measured during supine exercise, and the effects of supine training generalize to the upright posture to a greater extent than the effects of upright training generalize to the supine posture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938734 TI - Increased resistance in postobstructive pulmonary vasculopathy: structure function relationships. AB - Postobstructive pulmonary vasculopathy (POPV) was produced by chronic ligation (120 days) of the left main pulmonary artery of seven dogs. To explain the abnormal physiological changes found using arterial and venous occlusion (AVO) in POPV (J. Appl. Physiol. 69: 1022-1032, 1990), the light-microscopic morphology, morphometry (n = 5), and ultrastructure (n = 6) of ligated left lower lobes were compared with contralateral control right lower lobes. First, there was a proliferation of bronchial vessels around pulmonary vessels and airways to explain bronchial blood flow rates of 330 ml/min in left lower lobes. The walls of the bronchial vessels contained smooth muscle with minimal elastic tissue and prominent myoendothelial junctions. Second, focal bronchopulmonary anastomoses were seen in pulmonary arteries approximately equal to 100 microns diam, which is consistent with our conclusion that the major site of communication is at the precapillary level and suggests that the limit between arterial and middle segments defined by AVO may lie in arteries of approximately equal to 100 microns. Third, to explain the increased arterial resistance in POPV, the pulmonary arteries had an increased percent medial muscle thickness, peripheral muscularization, and focal intimal thickening but had no plexiform lesions. The ultrastructure of the arteries revealed new intimal cells and numerous myoendothelial junctions rarely found in controls. Capillaries and veins were only subtly altered. Fourth, the hyperreactivity of arteries to serotonin and of veins to histamine found using AVO was partially explained by the increased medial thickness and decreased diameter but may also be due to increased receptor concentration or related to the myoendothelial junctions. We conclude that most of the hemodynamic alterations in POPV are related to morphological abnormalities and that this model has clinical and experimental relevance in the study of bronchopulmonary vascular interactions. PMID- 1938735 TI - Effect of increased acceleration on regional pleural pressure in dogs. AB - The variation of pleural pressure was measured in anesthetized spontaneously breathing dogs subjected to increased acceleration (0-4 G) in a centrifuge. Two groups of animals were studied. In one group, the resultant acceleration was in a direction either ventral-to-dorsal (+Gx) or dorsal-to-ventral (-Gx), with a relatively small residual cranial-to-caudal acceleration. In the other group, the resultant acceleration was either cranial-to-caudal (+Gz) or caudal-to-cranial ( Gz), with a relatively small residual dorsal-to-ventral acceleration. Pleural liquid pressure (Ppl) was measured by two rib capsules that were separated by 7-9 cm and oriented either in the dorsal-to-ventral or cranial-to-caudal direction. At functional residual capacity, Ppl in the nondependent lung region became more negative when the acceleration was in the +Gx or +Gz direction. Thus the lung would be susceptible to damage that results from overexpansion in these acceleration directions. By contrast, acceleration in the -Gx or -Gz direction produced values of Ppl at functional residual capacity that were positive. Thus, in these acceleration directions, the respiratory muscles must provide greater force during inspiration to overcome lung compression before lung ventilation can occur. The Ppl gradients with respect to the acceleration directions increased approximately in proportion to acceleration in the +Gx, -Gx, and -Gz directions but remained relatively constant in the +Gz direction. PMID- 1938736 TI - Gravity is a minor determinant of pulmonary blood flow distribution. AB - Regional pulmonary blood flow in dogs under zone 3 conditions was measured in supine and prone postures to evaluate the linear gravitational model of perfusion distribution. Flow to regions of lung that were 1.9 cm3 in volume was determined by injection of radiolabeled microspheres in both postures. There was marked perfusion heterogeneity within isogravitational planes (coefficient of variation = 42.5%) as well as within gravitational planes (coefficient of variation = 44.2 and 39.2% in supine and prone postures, respectively; P = 0.02). On average, vertical height explained only 5.8 and 2.4% of the flow variability in the supine and prone postures, respectively. Whereas the gravitational model predicts that regional flows should be negatively correlated when measured in supine and prone postures, flows in the two postures were positively correlated, with an r2 of 0.708 +/- 0.050. Regional perfusion as a function of distance from the center of a lung explained 13.4 and 10.8% of the flow variability in the supine and prone postures, respectively. A linear combination of vertical height and radial distance from the centers of each lung provided a better-fitting model but still explained only 20.0 and 12.0% of the flow variability in the supine and prone postures, respectively. The entire lung was searched for a region of contiguous lung pieces (22.8 cm3) with high flow. Such a region was found in the dorsal area of the lower lobes in six of seven animals, and flow to this region was independent of posture. Under zone 3 conditions, neither gravity nor radial location is the principal determinant of regional perfusion distribution in supine and prone dogs. PMID- 1938737 TI - Pressure-induced striatal dopamine release correlates hyperlocomotor activity in rats exposed to high pressure. AB - Free-moving rats chronically implanted in the striatum with multifiber carbon electrodes selective to dopamine were compressed in a helium-oxygen mixture to 80 bars. Extracellular dopamine level and behavioral symptoms of high-pressure neurological syndrome were simultaneously recorded. Under these conditions, the extracellular level of dopamine monitored by differential pulse voltammetry was found to be pressure dependent, and hyperlocomotor activity, a behavioral symptom of high-pressure neurological syndrome, was found to be linked to these pressure induced changes in dopamine release. PMID- 1938738 TI - A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women. AB - The isokinetic strength of the elbow and knee extensors and flexors was measured in 200 healthy 45- to 78-yr-old men and women to examine the relationship between muscle strength, age, and body composition. Peak torque was measured at 60 and 240 degrees/s in the knee and at 60 and 180 degrees/s in the elbow by use of a Cybex II isokinetic dynamometer. Fat-free mass (FFM) was estimated by hydrostatic weighing in all subjects, and muscle mass (MM) was determined in 141 subjects from urinary creatinine excretion. FFM and MM were significantly lower (P less than 0.001) in the oldest group. Strength of all muscle groups at both testing speeds was significantly (P less than 0.006) lower (range 15.5-26.7%) in the 65- to 78- than in the 45- to 54-yr-old men and women. When strength was adjusted for FFM or MM, the age-related differences were not significant in all muscle groups except the knee extensors tested at 240 degrees/s. Absolute strength of the women ranged from 42.2 to 62.8% that of men. When strength was expressed per kilogram of MM, these gender differences were smaller and/or not present. These data suggest that MM is a major determinant of the age- and gender-related differences in skeletal muscle strength. Furthermore, this finding is, to a large extent, independent of muscle location (upper vs. lower extremities) and function (extension vs. flexion). PMID- 1938739 TI - Effect of axillary blockade on regional cerebral blood flow during static handgrip. AB - Regional cerebral blood flow (rCBF) was determined at rest and during static handgrip before and after regional blockade with lidocaine. A fast rotating single photon emission computer tomograph system with 133Xe inhalation was used at orbitomeatal plane (OM) +2.5 and +6.5 cm in eight subjects. Median handgrip force during the control study was 41 (range 24-68) N, which represented 10% of the initial maximal voluntary contraction (MVC) and was 24 (18-36) N after axillary blockade (P less than 0.05), which represented 21% of the new MVC. During static handgrip, the rating of perceived exertion was 14 (10-16) exertion units before and 18 (15-20) after blockade (P less than 0.05). Hemispheric mean CBF did not change during handgrip. However, premotor rCBF increased from 55 (44 63) to 60 (50-69) ml.100 g-1.min-1 (P less than 0.05) and motor sensory rCBF from 57 (46-65) to 63 (55-71) ml.100 g-1.min-1 (P less than 0.05) to both the ipsilateral and contralateral sides during handgrip before, but not after, axillary blockade. There was no change in rCBF to other regions of the brain. Regional anesthesia with lidocaine did not alter resting rCBF. However, despite a greater sense of effort during static handgrip, there was no increase in rCBF after partial sensory and motor blockade. Thus bilateral activation occurs in the premotor and motor sensory cortex during static handgrip, and this activation requires neural feedback from the contracting muscles. PMID- 1938740 TI - Role of bronchial basement membrane in airway collapse. AB - Bronchial basement membrane is an elastic structure that has the potential to be load bearing and thus to contribute to the mechanical stiffness of the bronchus. To investigate this possible role, the membrane was modeled as a thin-walled linearly elastic tube surrounded by a uniform liquid on the outside and by air on the inside. When the external pressure on such a tube exceeds the internal pressure by a critical amount, the tube buckles reversibly into two or more folds. The critical buckling pressure varies as the square of the number of folds. The analysis was used to investigate the collapse behavior of the model tube into patterns ranging from 2 to 24 folds. This showed that the resistance to collapse increases rapidly as the number of folds increases. Data in the literature lead to the conclusion that the pressures involved in collapsing the tubes are probably in the physiological range. It is suggested, on the basis of the model results reported here, that bronchial hyperresponsiveness could be related to the number of folds into which the basement membrane buckles when the bronchial muscle contracts. A reduced number of folds would yield an increased response. PMID- 1938741 TI - Enhanced protein breakdown after eccentric exercise in young and older men. AB - The effects of eccentric exercise on whole body protein metabolism were compared in five young untrained [age 24 +/- 1 yr, maximal O2 uptake (VO2max) = 49 +/- 6 ml.kg-1.min-1] and five older untrained men (age 61 +/- 1 yr, VO2max = 34 +/- 2 ml.kg-1.min-1). They performed 45 min of eccentric exercise on a cycle ergometer at a power output equivalent to 80% VO2max (182 +/- 18 W). Beginning 5 days before exercise and continuing for at least 10 days after exercise, they consumed a eucaloric diet providing 1.5 g.kg-1.day-1 of protein. Leucine metabolism in the fed state was measured before, immediately after, and 10 days after exercise, with intravenous L-[1-13C]leucine as a tracer (0.115 mumol.kg-1.min-1). Leucine flux increased 9% immediately after exercise (P less than 0.011) and remained elevated 10 days later, with no effect of age. Leucine oxidation increased 19% immediately after exercise and remained 15% above baseline 10 days after exercise (P less than 0.0001), with no effect of age. In the young men, urinary excretion of 3-methylhistidine per gram of creatinine did not increase until 10 days postexercise (P less than 0.05), but in the older men, it increased 5 days after exercise and remained high through 10 days postexercise (P less than 0.05), averaging 37% higher than in the young men. These data suggest that eccentric exercise produces a similar increase in whole body protein breakdown in older and young men, but myofibrillar proteolysis may contribute more to whole body protein breakdown in the older group. PMID- 1938742 TI - Effect of carbohydrate supplements and water on exercise metabolism in the heat. AB - Carbohydrate (CHO) supplements of different concentrations were compared with water to determine their effects on thermal regulation and plasma volume maintenance while subjects exercised for 2 h in the heat and to determine their impact on carbohydrate utilization. Trained cyclists (n = 12) rode at 48.8 +/- 0.8% maximal O2 consumption in an environmental chamber maintained at 33.0 +/- 0.1 degree C and 51.7 +/- 1.4% relative humidity on three separate occasions. During each exercise bout the subjects received 3 ml/kg body wt of H2O, a 2.0% glucose polymer (LC) solution, or an 8.5% glucose polymer (HC) solution every 15 min. Muscle biopsies from the vastus lateralis were obtained before and after the H2O and HC trials only. Rectal temperature and heart rate, but not O2 consumption, rose from the 10- to 120-min period of exercise. No differences among treatments were found for these variables. There were also no significant differences among treatments for percent changes in plasma volume and blood volume. Plasma glucose and insulin were unchanged during the H2O and LC trials but were significantly elevated during the HC trial. In addition, CHO oxidation was significantly greater during the HC trial than during the H2O trial from 60 to 120 min of exercise. However, the reduction in muscle glycogen during the HC trial (206.5 +/- 23.6 mumol/g protein) was significantly less (P less than 0.05) than during the H2O trial (342.3 +/- 41.9 mumol/g protein).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938743 TI - Interleukin 1 protects rats against oxygen toxicity. AB - We studied the effect of interleukin 1 alpha (IL-1) in the protection against O2 toxicity. Tracheal insufflation of IL-1 resulted in a dose-dependent protection against O2 toxicity. All control rats died within 3 days of O2 exposure. In contrast, 84, 71, and 20% of rats insufflated with 5, 1, and 0.2 microgram(s) IL 1 (150, 30, and 6 x 10(4) U), respectively, survived 100% O2 exposure for greater than 11 days. At 2.3 days after O2 exposure, control rats showed severe pulmonary injury, which insufflation of 5 microgram(s) IL-1 markedly attenuated. The protection against O2 toxicity was associated with a selective enhancement of pulmonary Mn-superoxide dismutase (Mn-SOD) activity in IL-1-insufflated rats. In rats insufflated with IL-1 that survived exposure to 100% O2 for 7 days, the activities of pulmonary Mn-SOD, Cu,Zn-SOD, catalase, and glutathione peroxidase were all increased. The increased pulmonary Mn-SOD activity demonstrated in IL-1 insufflated rats at 2.3 days after O2 exposure may contribute to the protection against acute O2 toxicity, and the markedly increased activities of all pulmonary antioxidant enzymes shown in rats insufflated with IL-1 that survived O2 exposure for 7 days may in part be responsible for the chronic adaptation of these rats to a 100% O2 environment. PMID- 1938744 TI - Accuracy of measurements of small changes in soft tissue mass by use of dual photon absorptiometry. AB - Dual-photon absorptiometry (DPA) has recently been applied to the assessment of body composition. To evaluate the accuracy of DPA in detecting small changes in the lean soft tissue mass, we performed DPA with the use of the Norland 2600 Dichromatic densitometer on six healthy adult males before and after a 30-ml/kg transfusion of saline and before and after exercise in a warm environment, resulting in a greater than or equal to 1-kg weight loss. Absolute weight [baseline pretransfusion r2 = 0.999, standard error of estimate (SEE) = 590 g; posttransfusion r2 = 0.999, SEE = 300 g; baseline pretranspiration r2 = 0.999, SEE = 230 g; posttranspiration r2 = 0.999, SEE = 240 g] was accurately reflected in DPA total mass. Weight changes due to transfusion were poorly reflected by changes in DPA total mass (r2 = 0.417, SEE = 404 g). However, changes posttranspiration were accurately reflected in the DPA total mass (r2 = 0.886, SEE = 106 g posttranspiration). Similarly, weight changes due to transfusion were poorly measured by changes in DPA soft mass (r2 = 0.478, SEE = 365 g), but changes posttranspiration were highly correlated with DPA soft mass changes (r2 = 0.909, SEE = 92 g). Weight changes were not reflected by changes in the DPA lean soft tissue mass (r2 = 0.006, SEE = 1,737 posttransfusion, r2 = 0.094, SEE = 1,038 g posttranspiration). DPA-derived nonfat mass was highly correlated with skinfold-derived nonfat mass (r2 = 0.96, SEE = 2,400 g). Accuracy of total and soft tissue measurements implied correct mineral mass assessment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938745 TI - Effects of cold on microvascular fluid movement in the cat limb. AB - We investigated the effects of low temperatures down to approximately 5 degrees C on postcapillary resistance (Rv) and isogravimetric capillary pressure (Pci) in the isolated constant-flow-perfused cat hindlimb to see if a low-temperature induced increase in Rv and decrease in Pci could lead to an increase in filtration pressure and edema formation. A low-viscosity perfusate (20% cat plasma, 80% albumin-electrolyte solution; viscosity approximately 1 cP) was used. Isoproterenol (10(-7) M) was added to vasodilate the limb and achieve normal microvascular permeability. Rv and Pci were estimated from the slope and zero flow intercept, respectively, of the straight-line fit to the isogravimetric venous pressure vs. flow data. Rv and Pci were determined in each experiment at an initial 37 degrees C control, at a lowered temperature (30, 23, 15, or 5-10 degrees C), and then at 37 degrees C again. The ratio of Rv at the low temperatures relative to the initial 37 degrees C control increased almost linearly as temperature was reduced. The increase was 3.4 times control at the lowest temperature. Pci decreased significantly from control only in the lowest temperature group where the change was -5.4 mmHg. Analysis of our data with the low-viscosity perfusate shows that the limb can become edematous if temperature is lowered to approximately 5 degrees C unless venous pressure (Pv) is lowered to venous collapse and flow reduced to less than approximately 20 ml.min-1.100g 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938746 TI - Effects of hypoxia and hypercapnia on geniohyoid contractility and endurance. AB - Sleep apnea and other respiratory diseases produce hypoxemia and hypercapnia, factors that adversely affect skeletal muscle performance. To examine the effects of these chemical alterations on force production by an upper airway dilator muscle, the contractile and endurance characteristics of the geniohyoid muscle were examined in situ during severe hypoxia (arterial PO2 less than 40 Torr), mild hypoxia (PO2 45-65 Torr), and hypercapnia (PCO2 55-80 Torr) and compared with hyperoxic-normocapnic conditions in anesthetized cats. Muscles were studied at optimal length, and contractile force was assessed in response to supramaximal electrical stimulation of the hypoglossal nerve (n = 7 cats) or geniohyoid muscle (n = 2 cats). There were no significant changes in the twitch kinetics or force frequency curve of the geniohyoid muscle during hypoxia or hypercapnia. However, the endurance of the geniohyoid, as reflected in the fatigue index (ratio of force at 2 min to initial force in response to 40-Hz stimulation at a duty cycle 0.33), was significantly reduced by severe hypoxia but not by hypercapnia or mild hypoxia. In addition, the downward shift in the force-frequency curve after the repetitive stimulation protocol was greater during hypoxia than hyperoxia, especially at higher frequencies. In conclusion, the ability of the geniohyoid muscle to maintain force output during high levels of activation is adversely affected by severe hypoxia but not mild hypoxia or hypercapnia. However, none of these chemical perturbations affected muscle contractility acutely. PMID- 1938747 TI - Lung edema formation following inhalation injury: role of the bronchial blood flow. AB - We investigated the contribution of the bronchial blood flow to the lung lymph flow (QL) and lung edema formation after inhalation injury in sheep (n = 18). The animals were equally divided into three groups and chronically prepared by implantation of cardiopulmonary catheters and a flow probe on the common bronchial artery. Groups 1 and 2 sheep were insufflated with 48 breaths of cotton smoke while group 3 received only room air. Just before injury, the bronchial artery of group 2 animals was occluded. The occlusion was maintained for the duration of the 24-h study period. At the end of the investigation, samples of lung were taken for determination of blood-free wet weight-to-dry weight ratio (W/D). Inhalation injury induced a sevenfold increase in QL in group 1 (7 +/- 1 to 50 +/- 9 ml/h; P less than 0.05) but only a threefold increase in group 2 (10 +/- 2 to 28 +/- 7 ml/h; P less than 0.05). The mean W/D value of group 1 animals was 23% higher than that of group 2 (5.1 +/- 0.4 vs. 3.9 +/- 0.2; P less than 0.05). Our data suggest that the bronchial circulation contributes to edema formation in the lung that is often seen after the acute lung injury with smoke inhalation. PMID- 1938749 TI - Dynamic performance of a load-moving skeletal muscle. AB - The dynamic response of the tibialis anterior muscle of the cat was determined while it was subjected to sinusoidally varying orderly stimulation of motor units and to different isotonic loads in the range of 14-85% of the maximal isometric force. The dynamic response consisted of three major components: the displacement gain, the displacement attenuation, and a pure time delay. The displacement gain was dependent on the passive load applied to the muscle and the active force generated during contraction, which could be determined from the length-tension relationships and the corresponding shortening velocity. In general, the load displacement decreased as the load mass increased from 25 to 85% of the maximal isometric force. For loads less than 25% of the maximal isometric force, slight decrease in displacement was consistently observed. The displacement attenuation was dependent on the contraction frequency but uniform for all the load masses applied to the muscle. A pure time delay of 5 ms was present and accounted for various physiological processes such as conduction time in nerve and muscle, neuromuscular junction transmission, and excitation-contraction coupling. A quantitative equation was developed to describe the muscle's dynamic response under isotonic conditions and for a wide range of loads for use in various applications. PMID- 1938748 TI - Pulmonary surfactant will secure free airflow through a narrow tube. AB - Well functioning pulmonary surfactant is necessary to ensure alveolar stability. It is proposed that surfactant is also required to keep the finest cylindrical airways open, thereby securing an unrestricted flow of air to and from the alveoli. If the surfactant is inadequate in quality or quality there is a risk that liquid will accumulate in the most marrow section of the airway and form a blocking column. To study that possibility special glass capillaries were used. The glass capillaries were heated and extended to make a short section very narrow. In the lumen of that section a minute volume (1 microliter) of liquid was deposited, which formed a blocking column. When pressure was raised on one side of the column, it forced the liquid to move away from the narrow section. Pressure dropped to zero as air could pass, and if the liquid column consisted of calf lung surfactant extract (CLSE), pressure remained at zero because a new liquid column did not form. If, on the other hand, the liquid column consisted of saline solution it would repeatedly reform as soon as it had been pressed out of the capillary's narrow section. The same occurred if the CLSE suspension forming the liquid column was very dilute or contained inhibiting proteins. These observations did not require that the capillary consisted of the material glass; they were also noted when the narrow tube was outlined by epithelium. PMID- 1938750 TI - Modeling the effect of flow heterogeneity on coronary permeability-surface area. AB - In 11 anesthetized pigs, the left anterior descending coronary artery (LAD) was cannulated and pump perfused with blood before and during maximum adenosine vasodilation. For LAD plasma flows (F) ranging from 0.42 to 3.6 ml.min-1.g perfused tissue-1, we injected radiolabeled microspheres to measure heterogeneity and used the multiple indicator-dilution method to measure permeability-surface area product (PS) for EDTA. Heterogeneity of flow from the LAD was expressed as relative dispersion (RD) = standard deviation of flow/mean flow. Values of RD, corrected for tissue sample size using fractal theory, ranged from 13 to 87%, approaching 16-35% at high F. We developed a "variable-recruitment model" of regional heterogeneous capillary transport to correct PS for flow heterogeneity and capillary surface area recruitment. Values of PS ranged from 0.14 to 0.96 ml.min-1.g-1. Accounting for heterogeneity increased PS values by 0-18% compared with homogeneous values. Results revealed PS to be proportional to flow up to F = 1.5-2.1 ml.min-1.g-1 and then was constant at higher flows. The initial increase of PS with F may be due to capillary recruitment. When full recruitment is reached, PS becomes independent of F. We conclude that flow heterogeneity is significant but not readily predictable in the pig myocardium and that the use of microspheres to correct indicator-dilution data for flow heterogeneity improves the interpretation of multiple-tracer studies, particularly when tracers are used to study interventions that may alter flow distribution. PMID- 1938751 TI - Measurement of total respiratory impedance in infants by the forced oscillation technique. AB - The forced oscillation technique according to Landser et al. (J. Appl. Physiol. 41:101-106, 1976) was modified for use in infants. Adaptations, including a flexible tube to connect the infant to the measuring system and a bias flow to avoid rebreathing, did not influence impedance values. The linearity of the respiratory system was assessed and confirmed by 1) applying pseudo-random noise oscillations at three different amplitudes to 7 infants and 2) comparing in 12 infants impedance values obtained with pseudo-random noise and with sinusoidal oscillations at 12 and 32 Hz. Intersubject variability, averaged for all frequencies, was 6%. In 17 infants the relative error (+/- SD) between two series of five measurements within a time interval of 15 min was 0.5 +/- 5.7%. No statistically significant difference was found between impedance values before and after repositioning of the infant's head, whereas rotation resulted in a decrease in resistance and no effect on reactance. Our results indicate that the infant-adapted forced pseudo-random noise oscillation technique has the potential to give valuable information about ventilatory lung function in infants. PMID- 1938752 TI - Overexpansion pulmonary edema. PMID- 1938753 TI - Myeloablative therapy for follicular lymphoma. AB - Myeloablative therapy with autologous bone marrow transplantation is currently being investigated in follicular lymphoma. The number of patients treated to date is small and the follow-up time relatively short. However, the preliminary results warrant further evaluation. PMID- 1938754 TI - Radiolabeled monoclonal antibodies in the treatment of non-Hodgkin's lymphoma. AB - The use of radiolabeled monoclonal antibodies in the treatment of non-Hodgkin's lymphoma offers the hope of delivering radiation to tumor with relative specificity, thereby providing significant antitumor effects with limited toxicity. In this article the results of recently initiated trials are summarized, and the major unresolved issues concerning this approach are reviewed. PMID- 1938755 TI - Cytokines in the pathogenesis and management of non-Hodgkin's lymphomas. AB - Recombinant DNA technology has made possible the analysis of cytokine gene expression in both in vitro and in vivo studies of human hematopoietic malignancies and has facilitated the production of large amounts of recombinant cytokines. This development has led to advances in our understanding of the role of aberrant cytokine production in these diseases. These results support the concept of autocrine stimulation of leukemic growth, for instance, in multiple myeloma and acute myelogenous leukemia, and may lead to new therapeutic concepts such as the application of antibodies directed against these cytokines. Availability of recombinant cytokines has also allowed clinical testing in settings of disease- or therapy-related neutropenias and anemias, and particularly GM-CSF, G-CSF, and EPO have proven efficient in this respect. Thus, there is the prospect of more dose-intensive chemotherapy protocols as well as combinations of different cytokines that may prove more effective than application of a single compound. PMID- 1938756 TI - Non-Hodgkin's lymphoma. PMID- 1938757 TI - The therapy of non-Hodgkin's lymphomas. Introduction and overview. AB - Non-Hodgkin's lymphomas represent a diverse group of diseases that require an extensive knowledge base in order for physicians to utilize state-of-the-art therapies. This introduction outlines the current classification schemes and combination chemotherapy plans utilized for the non-Hodgkin's lymphomas. PMID- 1938758 TI - Chromosomal aberrations in non-Hodgkin's lymphoma. Biologic and clinical correlations. AB - Molecular characterization of chromosomal aberrations in non-Hodgkin's lymphoma (NHL) has provided a basic understanding of mechanisms of oncogene deregulation. Cytogenetic aberrations have been correlated with histologic subtype, immunophenotype, and clinical features of NHL. Although the incomplete specificity of some of the observed associations may limit the routine use of these markers in a clinical setting, the utilization of cytogenetic analysis can contribute to the diagnosis and management of patients with NHL. PMID- 1938759 TI - Immunologic markers in non-Hodgkin's lymphoma. AB - The majority of non-Hodgkin's lymphomas (NHLs) are of B-cell lineage, with less than 20% of cases being of T-cell lineage. The B-cell NHLs phenotypically correspond to normal cells in the mid stages of normal differentiation. More specifically, by their expression of B-cell activation antigens, these tumors are the neoplastic counterparts of normal activated B cells. The follicular lymphomas -including the small cleaved, mixed small and large cell, and large cell types, as well as the small noncleaved cell (Burkitt's) lymphomas--represent malignant expansions of normal germinal center B cells by their expression of pan-B cell antigens, B-cell activation antigens, and CD10 (CALLA). The diffuse lymphomas also correspond to normal activated B cells. The small lymphocytic lymphomas express the low-affinity IL-2 receptor and CD5, both of which are induced on normal B cells following mitogen stimulation. The other diffuse B-cell NHLs similarly express activation antigens and resemble "transformed" B cells. The T cell NHLs generally correspond to normal activated CD4+ T cells. These tumors- which include most peripheral T-cell lymphomas, cutaneous T-cell lymphomas, and HTLV-I-associated adult T-cell leukemias/lymphomas--express antigens induced on activated T cells, including IL-2 and transferrin receptors (CD25 and CD71, respectively), as well as HLA-DR. The lymphoblastic lymphomas, which are generally of T-cell lineage, phenotypically correspond to stages of intrathymic differentiation, often by their coexpression of CD4 and CD8, as well as expression of CD1. It remains controversial whether the immunophenotype of lymphoblastic lymphoma differs significantly from T-cell acute lymphoblastic leukemia. Since immunologic heterogeneity of NHL was first observed, attempts have been made to employ the data as a prognostic variable. Early studies suggested that lineage derivation or expression of markers of proliferating cells affected outcome in NHL. However, these reports were often retrospective, included various histologies, and did not treat patients uniformly. More recent prospective studies with relatively uniformly treated patients, predominantly involving DLCL, suggest that certain immunologically defined subgroups may have significantly different clinical outcomes. However, additional clinical studies will be necessary before treatment options are based upon immunologic markers. PMID- 1938760 TI - Molecular biologic studies in the clinical evaluation of non-Hodgkin's lymphoma. AB - Recent advances in DNA technology have revealed new information about the biology of the non-Hodgkin's lymphomas that is both provocative and exciting. Because these technologies are just beginning to be applied to the clinical evaluation of the non-Hodgkin's lymphomas, the results of clinical studies must be regarded as preliminary. At this time we can only speculate on how they might lead to improved clinical management or provide the basis for new therapies. PMID- 1938761 TI - New biologic markers in non-Hodgkin's lymphomas. AB - Many of the tumor markers mentioned in this article may seem to be of only research or theoretic interest. However, many of those mentioned are likely to be of great clinical utility in the future. In particular, the strength of these immunohistochemical findings have been compared with standard clinical prognostic features (e.g., stage, age, B symptoms) and have been modeled to show independent prognostic relevance in both intermediate-grade and low-grade lymphomas. Beyond their predictive value, these markers have identified phenotypes that may serve as new therapeutic targets: (1) restoration of HLA loss with alpha and gamma interferons; and (2) restoration of tumor-infiltrating T-cell lymphocytes with interleukin-2. New phenotype-directed cytokine therapies seem compelling with this new knowledge. We await future prospective trials of phenotyping to further refine this new exciting prospect. PMID- 1938762 TI - Newly recognized variant forms of non-Hodgkin's lymphomas. AB - High-resolution ancillary diagnostic methods, in concert with conventional histomorphology, have allowed recognition over the past 8 years of distinct clinical-pathologic variants of non-Hodgkin's lymphomas. With the insights previously offered by these studies, the pathologist can establish, or at least strongly suggest, the diagnosis of these entities on the basis of conventional histomorphology alone. As always, clinical information is essential for arriving at the correct diagnosis. Allocation of a rapidly frozen block of tumor tissue is a convenient, reliable "insurance policy" for the optional application of immunophenotyping and, if necessary, genetic probe analysis to resolve unusual or subtle subclassification problems. Because of clinical management implications, hematologists and oncologists should be aware of these newly recognized variant forms of non-Hodgkin's lymphomas. PMID- 1938763 TI - The malignant lymphomas in Africa. AB - Africa, the "dark continent" and the source of such wonderful tales as King Solomon's Mines and Jock of the Bushveld, has an equally enthralling story to tell about malignant disease in general and the lymphomas in particular as they occur among its varied people. It is uncertain how far back in history contact existed with the rest of the world, primarily in the form of slave trading and colonization by, among others, the Portuguese and the British. Until recent times, however, Africa's secrets have remained largely undisturbed. Fragments of medical information are recorded in the diaries of those early, intrepid explorers, such as Albert Cook, Henry Stanley, David Livingstone, and Albert Schweitzer. However, it is only in recent years that the great natural experiments that have for so long been underestimated, and very much less understood, belatedly started to attract attention. Examples are the systematic studies by Denis Burkitt, who through perseverance unraveled the lymphoma that now bears his name, and the thought-provoking description of the immunoproliferative small intestinal disease carried out by the Cape Town group, with both illustrating the axiom that "the study of man is man." Despite such occasional outstanding achievements, there is still considerable paucity of data pertaining to the various lymphoreticular malignancies, so that only limited conclusions are possible. Certainly, lymphoma in Africa differs from that elsewhere in the world. In part, this may reflect a background of immunologic disturbance attributable to parasitic infestation, viral infection, rampant malnutrition, and the impact of a wide variety of vectors, such as mosquitoes, in disease transmission. Striking differences exist in the distribution of these tumors as the incidence and pattern are followed from the equator to the milder climates in the south. This confirmed phenomenon gives rise to the tantalizing suggestion that, to some significant extent, the changes reflect the influence of geography. Thus, there may be associated alterations in the fauna and flora that determine the presence of intermediary hosts that have an impact on the eventual expression of the malignant clone. Many questions remain unanswered. For example, how can the lower incidence of Hodgkin's disease and the predominance of high grade malignancies in the tropics and subtropics be explained? To what extent does the lymphocytic and plasmacytic hyperplasia, ascribed to intense antigenic stimulus in Burkitt's lymphoma and myeloma--perhaps even other lymphomas, such as IPSID--predispose the host to a mutational event that leads to the emergence of each distinctive neoplasm?(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1938764 TI - Non-Hodgkin's lymphomas in Asia. AB - The relative frequencies of the various histopathologic types of lymphomas are generally similar among Asian countries. Hodgkin's disease and follicular lymphomas are relatively rare in Asia. Among NHL, the Asians have a higher rate of aggressive NHL, as compared with the NCI data. Immunologic analysis revealed that PTCL is common in Asia. The relative frequency of PTCL is comparable among Chinese in Taiwan, the east coast of China, and Hong Kong, as well as in adult T cell leukemia/lymphoma (ATLL) nonendemic areas in Japan. The increased rate of T cell lymphomas in Asia is attributed to the low incidence of follicular lymphomas. The similar patterns of distribution in histopathologic and immunologic subtypes of NHL in Asia suggest that a common ethnic or geographic factor exists. To elucidate it, further detailed epidemiologic studies are needed. Primary extranodal NHL is slightly more prevalent in Asia than in the United States; the most frequent primary site is Waldeyer's ring in Japanese patients and the GI tract in Chinese patients. Primary small intestinal lymphoma in Asia showed the pattern of the Western type. Primary cutaneous lymphomas are rare in Asia. The clinical features of PTCL in Asia are comparable with those described in the United States, except for a predilection for the nasal/paranasal region. In Asia, outside Japan, ATLL has been reported only in Taiwan. The seroepidemiologic survey of carriers of ATLL showed the rate of seropositivity for HTLV-I in Taiwan was similar to that in nonendemic areas in Japan. The clinicopathologic features of ATLL in Taiwan and Japan are essentially identical. In children in Japan and Taiwan, Hodgkin's disease is much less frequent than in the West. However, the relative frequencies of the histopathologic and immunologic subtypes of childhood NHL in Japan and Taiwan do not differ significantly from those of the West. Although Burkitt's lymphoma in Japan and Taiwan is of nonendemic type, in India it may comprise both endemic and nonendemic types in almost equal number. PMID- 1938765 TI - Cough in children. PMID- 1938766 TI - Cough in children. PMID- 1938767 TI - Sensitivity of FEV1 response following one and two inhalations of albuterol: a pilot study. AB - Eleven patients entered a pilot study designed to evaluate the proportion of eligible responders following a single inhalation of albuterol aerosol, the degree of response, and the sensitivity to distinguish between one and two inhalations based on FEV1 response. Each patient received a single inhalation at 0 and 60 minutes. FEV1 was measured 30 and 60 minutes after each inhalation. Most patients (82%) responded to a single inhalation and the majority (73%) were capable of further response after two inhalations. This study design was able to distinguish FEV1 responses to one and two inhalations of albuterol and provide upward and downward sensitivity sufficient to detect major differences in products. PMID- 1938768 TI - Systemic allergic reactions to corticosteroids. AB - Allergic anaphylactic (type I) reactions to corticosteroid medications are uncommon; however, a number of well-documented cases have been reported. We present a review of the literature, and report on two patients who suffered anaphylaxis after injections of corticosteroids. The first patient, a registered nurse, was finally found to be sensitive to all corticosteroid preparations containing carboxymethylcellulose, as well as the pure carboxymethylcellulose. The second patient had positive skin tests to hydrocortisone, hydrocortisone sodium succinate, methylprednisolone sodium succinate, and suxamethonium. Both patients were tested on two occasions; four normal subjects were tested in parallel, and did not elicit any positive skin reaction. In patients with systemic severe reactions to injectable corticosteroids, we recommend careful and comprehensive skin testing with most available corticosteroids, as well as the components of the injectables. PMID- 1938770 TI - Asthma camp/education for living. PMID- 1938769 TI - Effect of milk ingestion on pulmonary function in healthy and asthmatic subjects. AB - Since Maimonides, it has been common in folk medicine to proscribe milk for asthmatics because its putative stimulation of mucus production can exacerbate asthma symptoms. A literature review, however, failed to reveal any data supporting this notion. We, therefore, compared the effects of ingesting 16 oz. of whole milk (16 g lipid), skim milk (2 g lipid), and water (each on a separate day) on: (1) forced expiratory volume in 1 second (FEV1), (2) forced expiratory flow at 50% of vital capacity (V50), and (3) pulmonary diffusing capacity (DLCO) in 11 asthmatic and 10 nonasthmatic subjects. Measurements were taken at 30 minute intervals for 3 hours. The two milk types did not significantly change FEV1 or V50 in either group, indicating that the amount ingested did not change airway resistance sufficiently to alter airflow parameters. In the asthmatic group, however, DLCO decreased progressively over the 3 hours by 6.8 +/- 1.4% (mean +/- SE) per hour after whole milk (maximum reduction = 21 +/- 1.4%) but not after water or skim milk. In the nonasthmatic group, no significant effects were observed on DLCO after any of the liquids. These data suggest that milk lipids can disturb gas exchange in asthmatic patients. PMID- 1938771 TI - Metaproterenol (Alupent) metered dose inhaler in children 5-12 years of age. AB - This multiclinic study was performed to evaluate the safety and efficacy of metaproterenol sulfate (Alupent) metered dose inhaler in children with asthma ages 5 to 12 years. A total of 268 children completed this study according to the protocol, having received either metaproterenol or placebo for 30 consecutive days. Full spirometric testing was done pre- and postdose on Days 1 and 30 for a total duration of 6 hours on each day. The results showed that metaproterenol was consistently superior to placebo in all pulmonary function parameters measured on Days 1 and 30. This difference was statistically significant for peak values and areas under the curves for both FEV1 and FEF25-75%. There were no significant side effects noted. We conclude that metaproterenol metered dose inhaler is safe and effective in the treatment of asthma in children ages 5 to 12 years. PMID- 1938772 TI - Relapse and repeated remission of asthma after cancer chemotherapy and secondary hormonal changes. PMID- 1938773 TI - Social policy on the use of aversive interventions: empirical, ethical, and legal considerations. AB - In an effort to address the controversy regarding the use of aversive interventions in the treatment of individuals with developmental disabilities, this paper presents a review of the literature on the efficacy of such interventions, along with brief reviews of the ethical and legal issues involved. In general, there appears to be empirical, ethical, and legal support for the continued availability of aversive interventions as treatment options, but only if sufficient safeguards are in place. PMID- 1938774 TI - Changes in cognitive and language functioning of preschool children with autism. AB - Preschool children with autism and their normally developing peers were compared on the Stanford-Binet IV and Preschool Language Scale before and after 1 school year. Both measures showed that although the children with autism functioned at a lower level than their normally developing peers, the children with autism had narrowed this gap after treatment, making a nearly 19-point increase in IQ and an 8-point gain in language quotient. The IQ measure remained stable for the normally developing peers while their language showed a 7.73-point increase. The data support the notion that young children with autism can make very significant developmental gains. PMID- 1938775 TI - Though disorder in high-functioning autistic adults. AB - Examined thought disorder in a sample (n = 11) of high-functioning autistic young adults and older adolescents (mean IQ = 83) utilizing objective ratings from the Thought, Language and Communication Disorder Scale (TLC Scale) and projective data from the Rorschach ink blots. Results from the TLC Scale pointed to negative features of thought disorder in this sample (e.g., Poverty of Speech). Rorschach protocols revealed poor reality testing and perceptual distortions in every autistic subject, and also identified several areas of cognitive slippage (e.g., Incongruous Combinations, Fabulized Combinations, Deviant Responses, Inappropriate Logic). Comparing TLC Scale and Rorschach results to schizophrenic reference groups, autistic subjects demonstrated significantly more Poverty of Speech and less Illogically on the TLC Scale, and on the Rorschach they evidenced features of thought disorder that are encountered also in schizophrenia. Results are discussed in relation to the measures employed, and to areas of similarity and difference between autism and schizophrenia. PMID- 1938776 TI - Exploring the experience of autism through firsthand accounts. AB - Two firsthand accounts from verbal, high-functioning individuals with autism are presented. Participants include a 27-year-old man and a 13-year-old boy and his parents. Data collection included participant observation, formal and informal interviewing, correspondence, and collection of personal documents such as poems, art work, and essays. It was our aim to explore the participants' perceptions, mental processes, and experiences of living with autism. Five salient themes are identified and discussed: sensory processing, memory, stereotypical behaviors, social interaction, and empathy. Multichanneled sensory processing appeared in both participants, as well as a remarkably detailed memory of past events. Both participants were able to bring their stereotypical behaviors under voluntary control as a result of their awareness of nonautistic individuals' reactions to these behaviors. PMID- 1938777 TI - An investigation of the calendar calculation ability of a Chinese calendar savant. AB - A Chinese calendar savant was investigated on his exceptional proficiency in calendar calculation and his culture-specific talent of converting the Gregorian calendar to the Chinese calendar. Results did not support any one of the hypotheses of eidetic imagery, high-speed calculation, rote memorization, keying off (anchoring) strategy, use of calendar regularities or monthly configuration as the only explanation proposed in earlier investigations. The savant's calculation ability is hypothesized to be brought about by his familiarity of the 14 calendar templates and the knowledge of matching the templates to every year. For dates that are beyond the 20th century, the calculation is by regressing the date to a corresponding year in the 20th century by additions or subtractions of 28 or 700 years with his accurate use of the simple operations in arithmetic. PMID- 1938778 TI - Brainstem auditory evoked potential study in children with autistic disorder. AB - Brainstem auditory evoked potentials were compared in 109 children with infantile autism, 38 with autistic condition, 19 with mental retardation, and 20 normal children. Children with infantile autism or autistic condition had significantly longer brainstem transmission time than normal (p less than .001). Autistic features, rather than age, sex, or lower mentality, correlated with brainstem transmission time (p less than .0001). The autistic characteristics may be related to dysfunction of the brainstem which affects the processing of the sensory input through the auditory pathway. The brainstem lesion may be part of a generalized process of neurological damage that accounts for the deviant language, cognitive, and social development in the spectrum of autistic disorder. PMID- 1938779 TI - Brief report: biological factors associated with Asperger syndrome. PMID- 1938780 TI - Brief report: violence in Asperger syndrome, a critique. PMID- 1938781 TI - Brief report: effects of fenfluramine on communicative, stereotypic, and inappropriate behaviors of autistic-type mentally handicapped individuals. PMID- 1938783 TI - Current developments in the understanding of mental retardation. Part I: Biological and phenomenological perspectives. AB - During the past decade, noteworthy advances have taken place within the field of mental retardation. The application of advanced biological techniques in such areas as molecular genetics and neuroimaging has substantially improved our ability to identify the biological factors that underlie the origin and pathogenesis of an increasing number of mental retardation syndromes. Refined genetic and psychosocial assessments have highlighted the impressive degree of heterogeneity that is present within and across many mental retardation syndromes, stimulating increasing interest and study. This, the first of a two part review, will focus on recent developments in biological and phenomenological aspects of mental retardation. PMID- 1938782 TI - Brief report: haloperidol treatment of trichotillomania in a boy with autism and mental retardation. PMID- 1938784 TI - Impact of HIV on child and adolescent psychiatry. PMID- 1938785 TI - Child and adolescent psychiatrists and HIV disease: a survey. AB - During the spring and summer of 1989, all members of the American Academy of Child and Adolescent Psychiatry in nine states were sent questionnaires to determine the extent of child and adolescent psychiatrists' human immunodeficiency virus (HIV)-related knowledge, experience, comfort in working with HIV patients, and opinions regarding perceived educational needs about HIV. The response rate was 54% (N = 511). Two-thirds of the respondents indicated they had treated or had consulted on an HIV-infected patient. Most psychiatrists indicated reasonable comfort in working with HIV patients. Knowledge about HIV was found to be variable. Results suggest that child psychiatrists are engaging in HIV-related activities in all parts of the country, and further information or education would be welcomed by a majority of Academy members, particularly at nationally sponsored events. PMID- 1938786 TI - An AIDS education and prevention program for hospitalized adolescents. AB - This paper describes the development of a human immunodeficiency virus Prevention Program for a University-based adolescent psychiatric unit. The intervention spans 8 days with components in school, activity therapies, and a specific group that teaches sexual education. Important aspects that have contributed to the success of this intervention include its integration into a general sex education program, the utilization of the psychiatric milieu for promotion of the intervention, the participation of a person with acquired immune deficiency syndrome (AIDS) in the educational process, "high tech" components, such as attractive well-designed videos, and assessment and evaluation. The importance of AIDS education for psychiatrically hospitalized adolescents will be further elaborated. PMID- 1938787 TI - Prevalence and correlates of cutting behavior: risk for HIV transmission. AB - The prevalence of cutting behavior among a population of 76 psychiatrically hospitalized adolescents was found to be 61.2%. The frequency ranged from a single occasion to over 50 instances, with a mean of 9.9 occasions. Increased self-mutilation was not found to be associated with gender, age, ethnicity, or primary psychiatric diagnosis. A significant association was identified between adolescents who report forced sex and those who report cutting behavior. Approximately 26.7% of those reporting this behavior also report sharing cutting implements with other adolescents. This article raises concern about this behavior as it relates to the transmission of human immunodeficiency virus and makes recommendations for clinicians treating this population. PMID- 1938788 TI - Fear of AIDS related to development of obsessive-compulsive disorder in a child. AB - Fear of acquired immune deficiency syndrome (AIDS) has been associated with a variety of psychiatric disorders in adults and in some adolescents. A case is reported of a child with an unrealistic fear of AIDS who developed an obsessive compulsive disorder. This case illustrates the importance of providing adequate AIDS information to children. PMID- 1938790 TI - Adolescents with ADHD: patterns of behavioral adjustment, academic functioning, and treatment utilization. AB - Adolescents with attention deficit hyperactivity disorder (ADHD) were compared with a control group on a comprehensive assessment battery. More ADHD teenagers had oppositional defiant disorder (68%) and conduct disorder (39%) and were rated as more impaired in social competence, behavioral and emotional adjustment, and school performance by parents and teachers than control teens. The ADHD youths, however, rated themselves as better adjusted than did their parents and teachers, differing only from controls in depressive symptoms and antisocial acts. Poorer performances in verbal learning and vigilance and greater ADHD behaviors during a math task also distinguished the ADHD from control teenagers. PMID- 1938789 TI - Young adult mental status of hyperactive boys and their brothers: a prospective follow-up study. AB - This study reports on the psychiatric outcome as young adults (ages 16-23) of 50 hyperactive boys compared with their nonhyperactive brothers and to unrelated controls. Siblings provide a built-in control for potentially important factors, such as social class and parental psychopathology. Blind assessments at follow-up showed that significantly more probands (30%) than siblings (6%) and controls (10%) had multiple DSM-III diagnoses. Moreover, probands had a more severe form of antisocial disorder than siblings. In conclusion, the increased risk for multiple and more pervasive mental disorder in the young adulthood of hyperactive boys cannot be attributed to childhood factors shared with siblings. PMID- 1938791 TI - Treatment of ADHD with fluoxetine: a preliminary trial. AB - Nineteen children and adolescents with attention-deficit hyperactivity disorder were treated with fluoxetine hydrochloride. The drug was administered in an open label fashion for 6 weeks. At completion of the study, nearly 60% were judged to be at least moderately improved. No effects on appetite or weight were observed, and side effects were minimal. These findings suggest that fluoxetine may prove to be an alternative treatment for some attention-deficit hyperactivity disorder patients. PMID- 1938792 TI - Effects of dextroamphetamine on the cognitive and social play of a preschooler with ADHD. AB - This study investigates how deficits in attention and impulse control are reflected in the social and cognitive play of a 4-year-old boy with attention deficit hyperactivity disorder. In addition, an A-B-A-B reversal design was employed to evaluate the effectiveness of dextroamphetamine (2.5 mg, twice a day) for treatment of preschool attention-deficit hyperactivity disorder. The most dramatic effects of medication were observed on the level of sustained attention and the pattern of cognitive play. Sustained attention during play and in a structured group activity improved, and play became more sequentially organized and symbolic. Results are discussed with respect to the following: 1) attention deficit hyperactivity disorder and preschool play; 2) the efficacy of psychostimulant medication; and 3) the adequacy of teacher ratings versus direct observation in measuring medication response. PMID- 1938793 TI - Intranasal abuse of prescribed methylphenidate by an alcohol and drug abusing adolescent with ADHD. AB - A rare case is described where an adolescent with attention deficit hyperactivity disorder diagnosed in childhood subsequently developed alcohol and drug abuse. He later developed intranasal methylphenidate abuse and dependence after realizing that urine drug screens were expected to be positive for prescribed methylphenidate. This report is to alert physicians to the rare possibility of intranasal methylphenidate abuse in chemically dependent teenagers treated for ADHD and also to the possibility of group methylphenidate abuse at special education schools where many teenagers may be treated with stimulant medication. PMID- 1938794 TI - Physical and sexual abuse in childhood: relationship with post-traumatic stress disorder. AB - This study describes the reactions of children and adolescents to physical and/or sexual abuse, suggesting two distinct symptom pictures. Findings indicate that a majority (55%) of this clinical population develop symptoms characteristic of post-traumatic stress disorder, whereas abused children and adolescents who do not develop associated post-traumatic stress disorder symptoms exhibit more anxiety, depression, externalizing behaviors, and more problems overall. Significant differences were also found between children and adolescents reacting to single event abuse who display more behavior disorders and victims of ongoing abuse who appear significantly more disturbed, with symptoms ranging from depression to psychosis. PMID- 1938795 TI - Growth hormone response patterns in sexually or physically abused boys. AB - The ratio of growth hormone response to clonidine and L-dopa challenge was compared in 74 boys: 15 with purported physical abuse, 7 with purported sexual abuse, 13 normal controls, and 39 psychiatric controls. Sexually abused boys demonstrate a statistically significant elevated ratio of growth hormone response to clonidine versus response to L-dopa. Physically abused boys demonstrate lower clonidine/L-dopa growth hormone response ratios compared with controls. These effects widen with increasing physical development. PMID- 1938796 TI - Differentiating hypererotic states in the evaluation of sexual abuse. AB - When young children behave in a sexual manner, they may be suspected of having been sexually abused. However, this behavior may or may not indicate sexual abuse. Case studies suggest that nonsexually abused children can manifest an increase in erotic behavior on the basis of unusually intense but nonabusive sexual experiences or as part of a compulsion. When the sexual behavior is secondary to abuse, it can be related to posttraumatic stress disorder or intense and prolonged sexual experience. PMID- 1938797 TI - Adolescent suicidality: a clinical-developmental approach. AB - This study investigates the relation of ego development, age, gender, and diagnosis to suicidality among 219 adolescent psychiatric inpatients. Using the Diagnostic Interview Schedule for Children, adolescents were classified as suicide attempters or as nonsuicidal and were categorized into three diagnostic groups: affective disorder, conduct disorder, or mixed conduct-affective disorder. Ego development measurement was used to assess developmental maturity. Chi-square analyses demonstrated a relation between suicide attempts and developmental complexity. Attempters were more likely to be diagnosed with affective or mixed conduct-affective disorders and to be girls. Suicidality was not associated with age in this sample. Log-linear analyses demonstrated the interplay of known suicide risk factors with the important new dimension of developmental level. PMID- 1938798 TI - The 3-year longitudinal course of suicidality and predictive factors for subsequent suicidality in youths with major depressive disorder. AB - This study followed the course of suicidal thoughts and behaviors in youths 7 to 17 years of age who recently experienced an episode of major depression. Suicidal was expressed by 72% of the youths at some time during the study. These predominantly outpatient youths tended to be suicidal on multiple occasions, but their severity of suicidality did not increase over time. Three variables at presentation predicted later suicidality: severity of initial suicidality, anger, and age. These results suggest that milder forms of suicidality represent a feature of depression rather than characterizing a subgroup of high-risk depressed youths. The results also suggest that suicidality and anger may mark a predominantly irritable form of depression as youths mature. PMID- 1938799 TI - The impact of curriculum-based suicide prevention programs for teenagers: an 18 month follow-up. AB - In a long-term follow-up of a study designed to assess the impact of school-based suicide prevention curricula on high school students, a group of 174 students from two high schools who were exposed to a prevention program were compared with a group of 207 control students from two additional high schools who were not exposed to the curriculum. A questionnaire, designed to measure the effects of the prevention program on actual help-seeking behaviors and suicide morbidity during the follow-up period, was administered 18 months after delivery of the program. The study failed to find convincing evidence of any program effect. PMID- 1938800 TI - Methylphenidate and thioridazine in the treatment of intellectually subaverage children: effects on cognitive-motor performance. AB - Twenty-seven children (or smaller subgroups depending upon task difficulty and subject ability) with subaverage IQs took part in a double-blind, placebo controlled, cross-over study of methylphenidate (0.4 mg/kg/day) and thioridazine (1.75 mg/kg/day). The children were tested for IQ performance, breadth of attention, and performance on a series of electronically controlled cognitive motor tests. Methylphenidate improved accuracy on a memory task, reduced omission errors on an attentional task, and reduced seat movements on two tasks. Thioridazine failed to have any deleterious effects on IQ performance when subjects received reinforcers for correct answers. Thioridazine at the given dose did not adversely affect performance on any of the cognitive-motor performance tests. Methylphenidate appears likely to enhance sustained attention and motivation in appropriately selected children with mild developmental delays, whereas thioridazine at this modest dose does not appear to impair performance on most psychomotor tests. PMID- 1938801 TI - The prevalence of fragile X in a sample of autistic individuals diagnosed using a standardized interview. AB - The study examined 75 autistic individuals who met DSM-III-R criteria for autistic disorder at 5 years of age. Diagnosis was based on information elicited using a standardized interview for autism. Two of 75 (2.7%) autistic subjects expressed the fragile X marker (Xq27.3) in 40% of cells counted and had other affected family members. Two additional subjects expressed the fragile X anomaly at low rates (1%). These rates are compared with those reported in other studies. Methodological differences, which may underlie the varying rates reported across studies, are discussed. PMID- 1938803 TI - Biased reporting by parents undergoing child custody evaluations. AB - This study tested the hypothesis that a parent undergoing a child custody evaluation will bias his or her report of the children's symptoms in a direction that supports the parent's aim in the litigation. Parents in 196 court-ordered child custody evaluations rated their children using the Achenbach Child Behavior Checklist. Additional families undergoing evaluations of visitation disputes (N = 34) and custody/visitation disputes complicated by sexual abuse allegations (N = 15) were used as comparison groups to test alternative explanations of the findings. Results were strongly supportive of the hypothesis that parental bias was present and quantifiable. PMID- 1938802 TI - Imipramine treatment of ADHD in a fragile X child. AB - Fragile X syndrome, an X-linked genetic disorder, is the third most common cause of mental retardation. The following is a case of a 6-year-old boy with fragile X syndrome and its characteristic cognitive and behavioral symptomatology, including attention deficit hyperactivity disorder. In addition, this child experienced initial insomnia and nocturnal enuresis, problems not previously reported with fragile X. Previous pharmacological treatment of the syndrome's behavioral difficulties and attention deficit has included stimulants, folic acid, and neuroleptics. This is the first report of the successful use of imipramine. Imipramine also improved the boy's insomnia and enuresis, whereas methylphenidate caused an overall worsening of his condition. PMID- 1938804 TI - The U.S. Supreme Court on victimized children: the constitutional rights of the defendant versus the best interests of the child. AB - In deciding seven recent landmark child abuse cases, the U.S. Supreme Court has addressed and sought to balance the inherent conflict between the constitutional rights of the defendant and the best interests of the child. In four of the cases, the Court found that the interests of the child superseded the rights of the defendant. In three cases, the Court gave more validity to the constitutional rights of the defendant. The author examines the lengthy nature of such legal proceedings and the reasoning forming the basis for the Supreme Court's decisions. PMID- 1938805 TI - The cardiotoxicity of the tricyclics. PMID- 1938806 TI - Suicide in Japan. PMID- 1938807 TI - Does satanism exist? PMID- 1938808 TI - Fluoxetine mechanism of action. PMID- 1938809 TI - Hypomania with fluoxetine. PMID- 1938810 TI - Transient psychosis with fluoxetine. PMID- 1938811 TI - Fluoxetine side effects. PMID- 1938812 TI - The panic disorder controversy continues. PMID- 1938814 TI - Prosthetic valve problems. PMID- 1938813 TI - Pharmacotherapy of eating and behavioral problems. PMID- 1938815 TI - Umbilical transillumination: an accurate means to diagnose minimal ascites associated with umbilical hernias. AB - A new bedside clinical test for the diagnosis of minimal ascites associated with reducible umbilical hernia is described. This test is based on transillumination of the hernial sac in the knee-elbow position. The test is easy to perform and has no equivocal results. PMID- 1938816 TI - Metabolic and cardiac effects of Clistanthus collinus poisoning. AB - A prospective study of 11 cases of Clistanthus collinus leaf poisoning was undertaken to evaluate the mechanism of hypokalaemia that occurs in these cases. Continuous cardiac monitoring was done. Ventricular ectopics, ventricular tachycardia and fibrillation were the important arrhythmias. No atrioventricular blocks or other significant bradyarrhythmias were noted. The renal potassium loss was found to be very high (120 +/- 87.95 mEq/L) even in the presence of hypokalaemia and in spite of continuing drop in serum potassium concentration. Metabolic study established that renal potassium leak is the mechanism by which hypokalaemia was mediated. PMID- 1938817 TI - Changing response to diamidine compounds in cases of kala-azar unresponsive to antimonial. AB - Two hundred and forty patients of kala-azar unresponsive to antimonial were treated with pentamidines in a dose of 4 mg/kg body weight on alternate days for 20 injections. Of these, 175 were treated with pentamidine isethionate and 65 with pentamidine methane sulphonate (Lomidine). Clinical and parasitological cure were significantly higher with lomidine as compared to pentamidine isethionate. However, cardiovascular, gastrointestinal and metabolic toxicity including hyperglycaemia were more marked with lomidine. Mortality rate was also significantly (P less than .05) higher with lomidine therapy. Significantly lower clinical and parasitological cure and higher relapse rate were observed in the present study compared with an earlier study in which pentamidine was used in the same doses for 10-12 injections only. PMID- 1938818 TI - Clinical and computed tomography analysis of intracerebral haemorrhage. AB - The clinical records and computed tomography scans of 50 consecutive patients with intracerebral haemorrhage (ICH) were analysed. Putaminal (48%) and thalamic (16%) ICH comprised the largest group, followed by cerebellar haemorrhage (12%). Intraventricular haemorrhage was observed in 14 cases, a majority being secondary to parenchymal haemorrhage. Hypertension remained the most important risk factor, occurring in 64% of the whole group and 83% of those with putaminal ICH. No predisposing factors for the haemorrhage were identified in 28% of patients. Twenty-seven patients were comatose; the incidence of coma in association with intraventricular haemorrhage was 79%. At the third week, 13 patients had died, a mortality rate of 26%. PMID- 1938819 TI - Plasma renin activity in diabetics with and without microangiopathy. AB - Plasma renin activity was measured in ten diabetics with nephropathy, 10 uncomplicated diabetics and 10 normal healthy controls. All the groups were comparable for age, sex, and duration of diabetes. Plasma renin activity was found to be significantly lower in patients with nephropathy in comparison to uncomplicated diabetics and normal healthy controls. There was no correlation between plasma renin activity and mean blood pressure or degrees of renal failure. These findings raise the possibility that microangiopathic changes occurring in the glomeruli and juxta-glomerular apparatus may alter the renin angiotensin system. Also the finding of low renin in diabetics with nephropathy may modify management policies. PMID- 1938820 TI - Epilepsy as a manifestation of neurocysticercosis. AB - Epilepsy is the commonest manifestation of neurocysticercosis. Epilepsy was observed in 127 of 150 cases (84.7%) of neurocysticercosis seen over a period of 17 years. The basis of diagnosis was clinical presentation and concomitant evidence of extraneural cysticercosis in the pre-computed tomography (CT) scan era, and typical CT findings in later years. Eighty one cases (54%) who primarily presented as epilepsy without any neurological deficit have been analysed in detail. In the pre-CT period the occurrence of epilepsy as a presenting feature in neurocysticercosis was 43.5% whereas in later years it was 61.4%. Primary generalised seizure (49 cases) was more common than partial seizure (29) and partial complex seizure (3). Status epilepticus was seen in 6 cases. Magnetic resonance imaging, done in 8 cases, proved to be more sensitive in demonstrating various stages in the development of noncalcified cysticercosis. The new larvicidal drugs offer a potential cure and cysticercosis should be entertained as a cause of epilepsy especially in endemic areas. PMID- 1938821 TI - A prospective study of 14 cases of motor neuron disease. AB - Fourteen consecutive patients with motor neuron disease were studied during a period of one year. Seven patients were in the second decade of life, with eleven below the age of 40 years. Males accounted for 13 cases. Four had sustained some trauma in the past, one had poliomyelitis. Younger patients (average age 17.9 years) usually had an asymmetrical lower motor neuron lesion which was gradually progressive (the Norris score reached an average of 89.9 in a mean period of 36.9 months). A largely symmetrical distribution affecting both the upper and lower motor neurons and the lower cranial nerves with a rapidly downhill course (the Norris score fell to 80.3 in 12.9 months) were the features observed in older patients (average age 46.7 years). Cerebrospinal fluid protein was raised in four cases. Anti-neural antibodies were not demonstrable in any of the patients. PMID- 1938822 TI - Thrombolytic therapy in clotted prosthetic mitral valve. AB - Thrombosis of a Bjork-Shiley valve in the mitral position was suspected clinically and confirmed by echocardiography and cine fluoroscopy. Streptokinase therapy followed by intravenous heparin infusion was given and the clot lysed successfully. The patient was asymptomatic upto two years of follow-up. PMID- 1938823 TI - Juxta splenic hydatid cyst. AB - A forty year old female who presented with intra-abdominal lump in the left hypochondrium was clinically suspected to have a juxta splenic hydatid cyst. Histopathology and cytology of the specimen removed at surgery confirmed the diagnosis. PMID- 1938824 TI - Homozygous familial hypercholesterolaemia. Report of three cases. AB - Homozygous familial hypercholesterolaemia is a rare disorder encountered in one in a million in the general population. Case reports of three patients from two families are presented. A 25 year male presented with extensive myocardial infarction and had a fatal outcome. His younger brother (14 years), as also a 12 year girl from another family with multiple planar xanthomata and tuberose xanthomata, are presented. PMID- 1938825 TI - Congenital factor XIII deficiency: two case reports. AB - Two patients with factor XIII deficiency, presenting with bleeding disorder since birth, are reported. The condition is rare and is likely to be missed unless clot solubility in 5 M urea is performed as a screening test in all patients with bleeding disorders. A correct diagnosis is essential as prophylactic management is practicable in this disorder. PMID- 1938826 TI - Boerhaaves' syndrome. AB - A 47 year old male with Boerhaaves' syndrome is described. A brief review of the literature is also presented. PMID- 1938827 TI - Enalapril induced persistent hypotension and acute renal failure. PMID- 1938828 TI - Coexistent hydatid disease and pulmonary tuberculosis in a five year old girl. PMID- 1938830 TI - Thyrotoxic vomiting. PMID- 1938829 TI - Intravenous magnesium in acute myocardial infarction. PMID- 1938831 TI - Acute renal failure due to acute diarrhoeal diseases. PMID- 1938832 TI - Insulin requirement formula. PMID- 1938833 TI - Rapid and simple method to control hyperglycaemia. PMID- 1938834 TI - Vasculitis--a complication of hypothyroidism. PMID- 1938835 TI - Metronidazole in acid peptic disease. PMID- 1938836 TI - Fluorosis in Maharashtra. PMID- 1938837 TI - Acute segmental enteritis presenting as lower gastrointestinal bleed. PMID- 1938838 TI - Cardiac involvement in rheumatoid arthritis. PMID- 1938839 TI - Familial hypercholesterolaemia in association with aortic stenosis. PMID- 1938840 TI - Neuroleptic malignant syndrome improved by bromocriptine. PMID- 1938841 TI - Megaloblastosis: a cause of false negative NESTROFT. PMID- 1938842 TI - Emergence of drug resistance in salmonellosis. PMID- 1938843 TI - The problem of emerging chloramphenicol resistance in typhoid fever--a preliminary report. AB - Drug sensitivity of Salmonella typhi isolated from 25 blood culture positive cases of typhoid fever who presented between May and July 1990 was tested to determine their in vitro susceptibility to various antimicrobials. Twenty-one of them (84%) showed resistance to chloramphenicol and 24 (96%) to cotrimoxazole. All the 25 cases were sensitive to norfloxacin, gentamicin and cephalexin. Sixteen of 21 chloramphenicol resistant typhoid cases in whom chloramphenicol was initially started failed to respond to this drug even after 5 to 7 days, thereby indicating that in vivo response matched with the in vitro sensitivity. Clinical response to norfloxacin, whether given initially or following chloramphenicol failure, was prompt and satisfactory. Norfloxacin thus appears to be a good choice in such cases. PMID- 1938844 TI - Some prospective observations on recent outbreak of typhoid fever in West Bengal. AB - The present study was designed to study the clinical behaviour of a recent epidemic of typhoid fever in West Bengal. Of 46 cases studied, 67% (31) had chloramphenicol resistant typhoid fever. The chloramphenicol-resistant cases were comparatively severe in nature with higher complication and mortality rates. Salmonella typhi resistant to chloramphenicol were also resistant to ampicillin, cloxaxillin and cotrimoxazole. Strains of Salmonella typhi sensitive to chloramphenicol retained their sensitivity to these other antimicrobials. PMID- 1938846 TI - Blood group and shigellosis. AB - A study on the distribution of ABO blood groups was carried out on 85 patients with clinically and bacteriologically proven shigellosis. A significant association (P less than 0.01) of blood group B was observed with shigellosis cases in comparison to controls from whom no Shigella species or other enteropathogen could be isolated. Patients with isoagglutinin B or those who possess blood group B antigen may be at a relatively increased risk of shigellosis. PMID- 1938845 TI - Preliminary observation on drug resistant cases of typhoid fever. AB - We report here a sudden and marked increase in the occurrence, in a captive population, of typhoid fever cases showing multiple drug resistance. Fifty one cases of typhoid fever were seen from January '90 to June '90 of which 49% showed multiple drug resistance. Comparative figures for resistance in the previous three years were 0% (1987), 5% (1988), 14% (1989). Shared resistance to chloramphenicol, ampicillin, amoxycillin and sensitivity to gentamicin, kanamycin, sisomycin, cephazolin, norfloxacin and ciprofloxacin in most of our cases suggest infection by a common strain with R-factor, mediated resistance. The illness was prolonged and associated with serious complications. Therapy with combination of quinolone derivatives and aminoglycoside antibiotics seemed justified on the basis of the in-vitro tests and clinical response. Efforts to identify the strain and stern public health measures to prevent further development of drug resistant S typhi are urgently indicated. PMID- 1938847 TI - Excessive polycythaemia of high altitude. Pulmonary function studies including carbon monoxide diffusion capacity. AB - Pulmonary function studies were done in 21 soldiers (low landers) posted at high altitude (average height 4773 metres) for prolonged periods (average 77.09 months), who had developed excessive polycythaemia, mean haemoglobin concentration being 23.06 g/dl. Studies revealed significant reduction in diffusion capacity of lungs which gradually returned to normal on sojourn at low altitudes for 70 days. Both the degree of polycythaemia and reduction in lung diffusion capacity were much more pronounced in smokers than in non-smokers. Vital capacity did not show any difference in these subjects while forced expiratory volume in 1 sec and ratio of forced expiratory volume to vital capacity (FEV1/VC) revealed only obstructive features in smokers. PMID- 1938848 TI - Blood carboxyhaemoglobin levels in smokers of Indian cigarettes with and without filters. AB - Blood carboxyhaemoglobin levels showed no significant difference between smokers of Indian cigarettes with and without filters (14.66 +/- 1.85 vs 16.07 +/- 1.92%; p greater than 0.05), although the value was slightly lower in the former. This may be because filters do not provide protection against absorption of carbon monoxide in the smoke. Further study in a large number is required. PMID- 1938849 TI - Effects of verapamil and nifedipine on psychomotor performance in human subjects. AB - The present study was undertaken to evaluate the effects of two structurally dissimilar calcium channel blockers, verapamil (a phenylalkylamine) in a single dose of 40 and 80 mg, and nifedipine (a dihydropyridine) in a single dose of 10 and 15 mg, on psychomotor performance and higher mental functions in human volunteers. Placebo and diazepam (5 mg) were used as negative and positive controls respectively. For evaluating these functions, tests employed were arithmetic ability, visual and auditory reaction time, letter (alphabet) cancellation, rapid fire arithmetic deviation and short term memory for playing cards. Careful record was kept of the heart rate, blood pressure and side effects of the therapy, each time the psychomotor tests were performed. Verapamil, both in 40 and 80 mg dose, was found to impair the performance of subjects to a significant extent in auditory reaction time, letter cancellation and short term memory. These effects were similar to those observed with administration of diazepam. With nifedipine, impairment in performance was observed only in rapid arithmetic deviation test. Thus, calcium channel antagonists, specially verapamil, impaired psychomotor performance of human subjects in our study. PMID- 1938850 TI - Effect of salbutamol on pulmonary diffusion functions in asymptomatic smokers. AB - Pulmonary functions including transfer factor for CO and its components (TIco, Dm, Vc) were studied in 45 asymptomatic subjects (25 smokers, 20 non smokers) using single breath technique. Ventilatory functions of smokers were significantly reduced; these improved significantly after salbutamol inhalation but most still remained lower than in non smokers. VA and Dm were marginally higher while Vc was significantly reduced in smokers. Their TIco1(20) was influenced only insignificantly. However, after salbutamol, both Dm and Vc were significantly lowered, resulting in further reduction (p 0.01) of TIco120 in smokers. The effect of salbutamol in non smokers was insignificant. PMID- 1938851 TI - Cirrhosis of liver simulating congenital cyanotic heart disease. AB - During the last 26 years, 21 patients with cirrhosis of the liver with severe cyanosis and gross clubbing simulating congenital cyanotic heart disease were subjected to cardiac catheterisation and angiography, splenography, liver function tests and liver biopsy. One patient had tetralogy of Fallot in addition, which was satisfactorily corrected. He continued to be intensely cyanosed and dyspnoeic despite adequate surgical correction of his cardiac defect as demonstrated on cardiac catheterisation and angiocardiography. Portupulmonary fistulas could not be demonstrated in any patient. The cyanosis and clubbing were secondary to right to left intrapulmonary shunting across multiple tiny pulmonary arteriovenous fistulas in all cases. In 16 cases selective pulmonary angiography revealed discrete arteriovenous fistulas. In 5 cases the angiogram did not reveal any convincing evidence of pulmonary arteriovenous fistulas. In 2 of these 5 cases peripheral vein contrast echocardiography, which seems to be a sensitive investigation, demonstrated right to left intrapulmonary shunting. Open lung biopsy in one case showed evidence of pulmonary arteriovenous fistulas. PMID- 1938852 TI - Food reduces isoniazid bioavailability in normal volunteers. AB - Food and drug interaction is a major variable in bioavailability of drugs. Isoniazid is the most common antitubercular drug used in India. We studied the effect of standard Indian breakfast and lunch on the bioavailability of isoniazid in a single dose crossover study in normal male volunteers. The standard breakfast and lunch significantly reduced plasma AUC, Cmax and Kabs values of isoniazid. Isoniazid, thus, should not be administered with food. PMID- 1938853 TI - Progressive supranuclear palsy. Report of 14 cases with special reference to unusual features. AB - The clinical features and course of 14 patients with progressive supranuclear palsy (PSP) were analysed. PSP formed 2.3 percent of the parkinsonian population. Blepharospasm, hypersomnia, athetosis, action dystonia, action myoclonus and family history of dementia were the unusual features. Half of the patients had dementia at presentation. Drug therapy was uniformly disappointing. The mean duration from onset to death in 4 patients who died was 4.5 years. The histopathological features in a patient with the disease for one year and who died of acute myocardial infarction showed moderately severe changes characteristic of the disease. PMID- 1938854 TI - Statistics for clinicians. 6. Interval data (II). PMID- 1938855 TI - Recombinant human erythropoietin (rHuEPO) in the treatment of anaemia of chronic renal failure. PMID- 1938856 TI - Acute necrotizing myelopathy with complete myelographic block. AB - Acute necrotizing myelopathy is a rare disorder. A case showing complete myelographic block extending from D3 to D6 level is described. The suspected aetiological factors for acute necrotizing myelopathy are discussed. PMID- 1938857 TI - Supravalvar aortic stenosis secondary to familial hypercholesterolaemia. Report of two cases. AB - Two cases of supravalvar aortic stenosis secondary to familial hypercholesterolaemia (type II A hyperlipoproteinaemia) are reported and the role of echocardiography in the diagnosis of this uncommon condition is discussed. The management of these patients is difficult and in one patient the serum cholesterol decreased substantially after treatment with gemfibrozil. PMID- 1938858 TI - Sphincteric involvement in organophosphorus poisoning. AB - Neurological complications like type II paralysis are well described in organophosphorus poisoning. Sphincteric involvement is not described. We report two patients of organophosphorus poisoning who had sphincteric involvement as an unusual manifestation of type II paralysis. PMID- 1938859 TI - Cerebral venous thrombosis in paroxysmal nocturnal haemoglobinuria--a complication of blood transfusion. PMID- 1938860 TI - Congenital hemihypertrophy: report of four cases. AB - Congenital hemihypertrophy is a rare condition. We came across four such cases within a period of six months. These cases are presented here and their unusual features highlighted. PMID- 1938861 TI - Mycobacterium tuberculosis infection presenting as pancytopenia with hypocellular bone marrow. PMID- 1938862 TI - Cardiac mesothelioma. AB - A patient with mesothelioma arising from the pericardium is being reported. The patient presented as a case of fever of unknown origin. PMID- 1938863 TI - Sodium valporate formulations. PMID- 1938864 TI - Prolactin levels in epilepsy. PMID- 1938865 TI - Nifedipine-induced gum hyperplasia. PMID- 1938866 TI - Nifedipine-induced gingival hyperplasia. PMID- 1938867 TI - Tetanus with hyperactivity of a portion of the platysma muscle. PMID- 1938868 TI - HIV infection after a solitary heterosexual contact. PMID- 1938869 TI - Spontaneous bacterial peritonitis and diaphragmatic movements. PMID- 1938870 TI - Cysticercal meningoencephalitis. PMID- 1938871 TI - Pathways for metabolism of ketoaldonic acids in an Erwinia sp. AB - The pathways involved in the metabolism of ketoaldonic acids by Erwinia sp. strain ATCC 39140 have been investigated by use of a combination of enzyme assays and isolation of bacterial mutants. The catabolism of 2,5-diketo-D-gluconate (2,5 DKG) to gluconate can proceed by two separate NAD(P)H-dependent pathways. The first pathway involves the direct reduction of 2,5-DKG to 5-keto-D-gluconate, which is then reduced to gluconate. The second pathway involves the consecutive reduction of 2,5-DKG to 2-keto-L-gulonate and L-idonic acid, which is then oxidized to 5-keto-D-gluconate, which is then reduced to gluconate. Gluconate, which can also be produced by the NAD(P)H-dependent reduction of 2-keto-D gluconate, is phosphorylated to 6-phosphogluconate and further metabolized through the pentose phosphate pathway. No evidence was found for the existence of the Entner-Doudoroff pathway in this strain. PMID- 1938872 TI - Pseudomonas aeruginosa outer membrane protein OprH: expression from the cloned gene and function in EDTA and gentamicin resistance. AB - Overexpression of major outer membrane protein OprH of Pseudomonas aeruginosa as a result of mutation (in strain H181) or adaptation to low Mg2+ concentrations (in parent strain H103) is accompanied by increased resistance to polymyxin B, gentamicin, and EDTA. A 2.8-kb EcoRI fragment containing the oprH gene was subcloned into several different expression plasmids in Escherichia coli. These experiments showed that significant levels of OprH could be produced from a promoter on the EcoRI fragment; that the cloned oprH gene was not regulated by Mg2+ deficiency; that there were no differences in the expression of OprH in any construction, regardless of whether the gene from strain H103 or its OprH overexpressing, polymyxin B-resistant derivative, strain H181, was used; and that overexpression of OprH in E. coli to the level observed in P. aeruginosa H181 did not result in a resistance phenotype. These results favored the conclusion that the mutation in strain H181 was a regulatory rather than a promoter mutation. The oprH gene was cloned behind the benzoate-inducible pm promoter in plasmid pGB25 and transferred to P. aeruginosa H103. Overexpression of OprH from the cloned gene in H103/pGB25 resulted in EDTA resistance but not polymyxin B resistance. This result suggested that another factor, possibly lipopolysaccharide, was affected by the mutation in strain H181. Consistent with this suggestion was the demonstration that mutants of strain H181 with alterations in lipopolysaccharide had reverted to wild-type polymyxin B susceptibility but had unaltered gentamicin and EDTA resistance. These data were consistent with the hypothesis that OprH replaces outer membrane-stabilizing divalent cations. PMID- 1938873 TI - Biochemical evidence for the existence of thymidylate synthase in the obligate intracellular parasite Chlamydia trachomatis. AB - Since eucaryotic cell-derived thymidine or thymidine nucleotides are not incorporated into Chlamydia trachomatis DNA, we hypothesized that C. trachomatis must obtain dTTP for DNA synthesis by converting dUMP to dTMP. In most cells, this reaction is catalyzed by thymidylate synthase (TS) and requires 5,10 methylenetetrahydrofolate as a cofactor. We used C. trachomatis serovar L2 and a mutant CHO K1 cell line with a genetic deficiency in folate metabolism as a host for chlamydial growth. This cell line lacks a functional dihydrofolate reductase (DHFR) gene and, as a result, is unable to carry out de novo synthesis of dTTP. C. trachomatis inclusions form normally when DHFR- cells are starved for thymidine 24 h prior to and during the course of infection. When [6-3H]uridine is used as a precursor to label C. trachomatis-infected CHO DHFR- cells, radiolabel is readily incorporated into chlamydia-specific DNA. When DNA from [6-3H]uridine labelled infected cultures is acid hydrolyzed and subjected to high-performance liquid chromatography analysis, radiolabel is detected in thymine and cytosine nucleobases. By using the DHFR- cell line as a host and [5-3H]uridine as a precursor, we could monitor intracellular C. trachomatis TS activity simply by following the formation of tritiated water. There is a good correlation between in situ TS activity and DNA synthesis activity during the chlamydial growth cycle. In addition, both C. trachomatis-specific DNA synthesis and 3H2O release are inhibited by exogenously added 5-fluorouridine but not by 5 fluorodeoxyuridine. Finally, we demonstrated in vitro TS activity in crude extracts prepared from highly purified C. trachomatis reticulate bodies. The activity is dependent on the presence of methylenetetrahydrofolic acid and can be inhibited with 5-fluoro-dUMP. Taken together, these results indicate that C. trachomatis contains a TS for the synthesis of dTMP. PMID- 1938874 TI - Deletion of spoIIAB blocks endospore formation in Bacillus subtilis at an early stage. AB - During an early stage of endospore formation in Bacillus subtilis, the cell divides asymmetrically into two compartments that follow different developmental paths. The differential expression of genes in these two compartments is controlled in part by the production of compartment-specific transcription factors, sigma G and sigma K. It is not known how sigma G accumulation is restricted to one of the two compartments, the forespore. However, the observations that sigma F directs transcription of the structural gene for sigma G and that sigma F activity can be modified by the product of a gene, spoIIAB, has led us to investigate the role of spoIIAB during sporulation. We have isolated mutants that carry deletion alleles of spoIIAB. Electron microscopic examination of these mutants revealed that these mutations blocked endospore formation at an early stage before septation and caused extensive cell lysis. The spoIIAB deletion alleles caused hyperexpression of genes that are normally expressed exclusively in the forespore compartments of sporulating wild-type cells, whereas these alleles reduced expression of other genes, including spoIIE, which is expressed before septation in wild-type cells. These observations confirm that spoIIAB is essential for sporulation and are consistent with models in which the product of spoIIAB plays a role in regulating the timing and/or compartment specificity of sigma F- and sigma G-directed transcription. PMID- 1938875 TI - Inactivation of the Escherichia coli priA DNA replication protein induces the SOS response. AB - Many of the proteins that operate at the replication fork in Escherichia coli have been defined genetically. These include some of the subunits of the DNA polymerase III holoenzyme, the DnaB replication fork helicase, and the DnaG primase. The multiprotein primosome (which includes the DnaB and DnaG proteins), defined biochemically on the basis of its requirement during bacteriophage phi X174 complementary-strand synthesis, could serve as the helicase-primase replication machine on the lagging-strand template. In order to determine if this is the case, we have begun an investigation of the phenotypes of mutants with mutations priA, priB, and priC, which encode the primosomal proteins factor Y (protein n'), n, and n", respectively. Inactivation of priA by insertional mutagenesis resulted in the induction of the SOS response, as evinced by induction of a resident lambda prophage, extreme filamentation, and derepression of an indicator operon in which beta-galactosidase production was controlled by the dinD1 promoter. In addition, the copy numbers of resident pBR322 plasmids were reduced four- to fivefold in these strains, and production of phi X174 phage was delayed considerably. These results are discussed in the context of existing models for SOS induction and possible roles for the PriA protein at the replication fork in vivo. PMID- 1938876 TI - Purification, cloning, and primary structure of a new enantiomer-selective amidase from a Rhodococcus strain: structural evidence for a conserved genetic coupling with nitrile hydratase. AB - A new enantiomer-selective amidase active on several 2-aryl propionamides was identified and purified from a newly isolated Rhodococcus strain. The characterized amidase is an apparent homodimer, each molecule of which has an Mr of 48,554; it has a specific activity of 16.5 mumol of S(+)-2-phenylpropionic acid formed per min per mg of enzyme from the racemic amide under our conditions. An oligonucleotide probe was deduced from limited peptide information and was used to clone the corresponding gene, named amdA. As expected, significant homologies were found between the amino acid sequences of the enantiomer selective amidase of Rhodococcus sp., the corresponding enzyme from Brevibacterium sp. strain R312, and several known amidases, thus confirming the existence of a structural class of amidase enzymes. Genes probably coding for the two subunits of a nitrile hydratase, albeit in an inverse order, were found 39 bp downstream of amdA, suggesting that such a genetic organization might be conserved in different microorganisms. Although we failed to express an active Rhodococcus amidase in Escherichia coli, even in conditions allowing the expression of an active R312 enzyme, the high-level expression of the active recombinant enzyme could be demonstrated in Brevibacterium lactofermentum by using a pSR1-derived shuttle vector. PMID- 1938877 TI - Telomere length constancy during aging of Saccharomyces cerevisiae. AB - It has been proposed that a decrease in the length of telomeres with the successive rounds of DNA replication that accompany mitotic division could play a causal role in the aging process. To investigate this possibility, telomeres from cells of the budding yeast Saccharomyces cerevisiae that varied in replicative age were examined. No change in the lengths of the telomeres was observed in cells that had completed up to 83% of the mean life span. We conclude that the length of the telomeres is not a contributing factor in the natural aging process in individual yeast cells. PMID- 1938878 TI - Identification of dcmR, the regulatory gene governing expression of dichloromethane dehalogenase in Methylobacterium sp. strain DM4. AB - The genes for dichloromethane utilization by Methylobacterium sp. strain DM4 are encoded on a 2.8-kb sequenced DNA fragment, the dcm region. This fragment contains dcmA, the structural gene of dichloromethane dehalogenase and, upstream of dcmA, a 1.5-kb region responsible for inducibility of dichloromethane dehalogenase by dichloromethane. A fragment of the dcm region covering dcmA and 230 bp of its upstream region was integrated into the chromosome of a Methylobacterium sp. strain DM4 mutant deleted for the dcm region. This yielded a strain expressin dichloromethane dehalogenase constitutively at the induced level. Plasmids carrying various segments of the 1.5-kb regulatory region were tested for their ability to restore regulation. The data obtained led to the identification of dcmR, the structural gene of a putative dcm-specific repressor. Transcription of dcmR was divergent from dcmA. dcmR encoded a 30-kDa protein with a helix-turn-helix motif near the amino terminus. The transcription start sites of dcmA and dcmR were identified by nuclease S1 mapping. The promoter regions of these genes contained nearly identical 12-bp sequences covering positions -14 to 25 relative to the mRNA start sites. Experiments with dcmR'-'lacZ fusions demonstrated that dcmR expression was markedly autoregulated at the level of transcription and less so at the protein level. These findings are compatible with both dcmA and dcmR expression being negatively controlled at the transcriptional level by the DcmR protein. PMID- 1938879 TI - The Psu protein of bacteriophage P4 is an antitermination factor for rho dependent transcription termination. AB - A 0.7-kbp DNA fragment from bacteriophage P4 that contained the polarity suppression (psu) gene was cloned in an expression plasmid. Induction of the plasmid-borne psu gene resulted in the overproduction of a protein having the biological properties of the P4-induced polarity suppressor. In vivo, Psu protein acted in trans to suppress rho-dependent polarity in the late genes of an infecting P2 phage, in plasmid operons, and in the host chromosome. Psu action did not require the presence of other P2 or P4 phage genes. Psu caused efficient readthrough (antitermination) by Escherichia coli RNA polymerase at the rho dependent terminators tR1 and TIS2, individually and in tandem, but did not affect termination at rho-independent sites. Neither the conserved antitermination sequence boxA nor any unique promoter or utilization sequence was required for Psu activity. PMID- 1938881 TI - Cloning and characterization of cutE, a gene involved in copper transport in Escherichia coli. AB - The copper-sensitive/temperature-sensitive phenotype of the Escherichia coli cutE mutant has been complemented by cloning wild-type genomic DNA into the plasmid vector pACYC184 and selecting transformants on medium containing 4 mM copper sulfate and chloramphenicol. One of these complementing clones, designated pCUT1, contained a 5.6-kb BamHI fragment. This recombinant plasmid transformed cutE, allowing wild-type growth of transformants on medium containing copper sulfate. Complementation of copper sensitivity was assessed by comparing both cell survival at increased copper levels and the results of 64Cu accumulation assays. An EcoRI subclone, 2.3 kb in size, was also shown to complement cutE when cloned in both medium- and high-copy-number vectors and was completely sequenced. This clone was mapped on the E. coli physical map at 705.70 to 707.80 kb. A series of subclones was constructed from pCUT1 and used to show that the large open reading frame of the translated sequence was essential for complementation. This open reading frame has a potential upstream promoter region, ribosome-binding site, and transcriptional terminator and encodes a putative protein of 512 amino acids that contains a region showing some homology to a putative copper-binding site. PMID- 1938880 TI - Characterization of the Butyrivibrio fibrisolvens glgB gene, which encodes a glycogen-branching enzyme with starch-clearing activity. AB - A Butyrivibrio fibrisolvens H17c glgB gene, was isolated by direct selection for colonies that produced clearing on starch azure plates. The gene was expressed in Escherichia coli from its own promoter. The glgB gene consisted of an open reading frame of 1,920 bp encoding a protein of 639 amino acids (calculated Mr, 73,875) with 46 to 50% sequence homology with other branching enzymes. A limited region of 12 amino acids showed sequence similarity to amylases and glucanotransferases. The B. fibrisolvens branching enzyme was not able to hydrolyze starch but stimulated phosphorylase alpha-mediated incorporation of glucose into alpha-1,4-glucan polymer 13.4-fold. The branching enzyme was purified to homogeneity by a simple two-step procedure; N-terminal sequence and amino acid composition determinations confirmed the deduced translational start and amino acid sequence of the open reading frame. The enzymatic properties of the purified enzyme were investigated. The enzyme transferred chains of 5 to 10 (optimum, 7) glucose units, using amylose and amylopetin as substrates, to produce a highly branched polymer. PMID- 1938882 TI - Molecular analysis of the Salmonella typhimurium phoN gene, which encodes nonspecific acid phosphatase. AB - The phoN gene of Salmonella typhimurium encodes nonspecific acid phosphatase (EC 3.1.3.2), which is regulated by a two-component regulatory system consisting of the phoP and phoQ genes. We cloned the phoN region into a plasmid vector by complementation of a phoN mutant strain and determined the nucleotide sequence of the phoN gene and its flanking regions. The phoN gene could encode a 26-kDa protein, which was identified by the maxicell method as the product of phoN. Results of the enzyme assay and Southern hybridization with chromosomal DNA of Escherichia coli K-12 suggests that there is no phoN gene in E. coli. The regulatory pattern of phoN in E. coli and Southern hybridization analysis of the E. coli chromosome with the S. typhimurium phoP gene suggest that E. coli K-12 also harbors the phoP and phoQ genes. PMID- 1938883 TI - Murein-metabolizing enzymes from Escherichia coli: sequence analysis and controlled overexpression of the slt gene, which encodes the soluble lytic transglycosylase. AB - The complete nucleotide sequence of the slt gene encoding the soluble lytic transglycosylase (Slt; EC 3.2.1.-) from Escherichia coli has been determined. The largest open reading frame identified on a 2.5-kb PvuII-SalI fragment indicates that the enzyme is translated as a preprotein of either 654 or 645 amino acids, depending on which of two potential start codons is used. The two possible translation products differ only in the lengths of their predicted signal peptides, 36 or 27 amino acids, respectively. In both cases, processing results in a soluble mature protein of 618 amino acids (Mr = 70,468). The deduced primary structure of the mature protein was confirmed by N-terminal sequencing and determination of the amino acid composition of the isolated transglycosylase. The slt gene contains a high percentage of rare codons, comparable to other low expressed genes. A hairpin structure that could serve as a transcriptional terminator is located downstream of the slt coding region and precedes the trpR open reading frame at 99.7 min on the E. coli chromosomal map. A computer assisted search did not reveal any significant sequence similarity to other known carbohydrate-degrading enzymes, including lysozymes. Interestingly, a stretch of 151 amino acids at the C terminus of the transglycosylase shows similarity to the N-terminal portion of the internal virion protein D from bacteriophage T7. Overexpression of the slt gene, under the control of the temperature-inducible phage lambda pR promoter, results in a 250-fold overproduction of the mature transglycosylase, whereas after deletion of the signal peptide a 100-fold overproduction of the enzyme is observed in the cytoplasm. PMID- 1938884 TI - Growth regulation of a Salmonella plasmid gene essential for virulence. AB - The Salmonella dublin plasmid gene vsdC is essential for virulence. We have constructed a vsdC-lacZ translational fusion to demonstrate that vsdC is selectively expressed during the stationary phase of bacterial cell growth. This pattern of expression has been confirmed by mRNA hybridization studies. Carbon starvation is able to induce vsdC expression by limiting bacterial growth. The expression of vsdC is dependent upon an upstream gene, vsdA, whose gene product possesses significant amino-terminus homology with the LysR family of transcriptional activator proteins. We have further demonstrated that vsdC expression is not dependent upon the known Salmonella chromosomal virulence regulatory loci ompR, phoP, and cya-crp and that vsdC can be expressed in a range of nontyphoidal Salmonella serovars, including some serovars in which introduction of the virulence plasmid does not confer mouse virulence. The vsd system provides a model for the study of transcriptional activation, a basis for the development of new expression vectors, and a novel mechanism of virulence gene regulation. Bacterial growth limitation within the phagosomes of host phagocytic cells may be the environmental signal inducing plasmid-mediated virulence gene expression in salmonellae. PMID- 1938885 TI - Targeted disruption of the Myxococcus xanthus orotidine 5'-monophosphate decarboxylase gene: effects on growth and fruiting-body development. AB - The Myxococcus xanthus gene coding for orotidine 5'-monophosphate (OMP) decarboxylase (EC 4.1.1.23) was cloned. The M. xanthus uraA gene efficiently complemented an Escherichia coli OMP decarboxylase mutant, permitting it to grow in the absence of uracil. Electroporation of M. xanthus with a circular plasmid carrying a selectable uraA::kan gene disruption resulted in homologous recombination at the chromosomal uraA locus. Chromosomal integration of the gene disruption plasmid created heterozygous (uraA+/uraA::kan) tandem duplications. These tandem duplications were unstable and segregated auxotrophic uraA::kan daughters at frequencies of 2 x 10(-4) to 8 x 10(-4) per viable cell. Rare uraA::kan segregants were easily obtained by selecting for resistance to the toxic analog 5-fluoroorotic acid. Our experiments suggest that the cloned uraA gene could facilitate the use of gene duplications in the genetic analysis of M. xanthus development. The uraA mutants could utilize uracil, uridine, or uridine 5'-phosphate for growth, indicating that M. xanthus has pyrimidine salvage pathways. During multicellular development, uraA::kan gene disruption mutants sporulated to wild-type levels but formed smaller and more numerous aggregates than did their uraA+ parent, regardless of whether uracil was added to the medium. Pyrimidine deprivation of uraA mutants, under conditions that otherwise supported vegetative growth, failed to induce fruiting-body development or sporulation. PMID- 1938887 TI - The spectrum of spontaneous mutations in a Saccharomyces cerevisiae uracil-DNA glycosylase mutant limits the function of this enzyme to cytosine deamination repair. AB - Uracil-DNA-glycosylase has been proposed to function as the first enzyme in strand-directed mismatch repair in eukaryotic organisms, through removal of uracil from dUMP residues periodically inserted into the DNA during DNA replication (Aprelikova, O. N., V. M. Golubovskaya, T. A. Kusmin, and N. V. Tomilin, Mutat. Res. 213:135-140, 1989). This hypothesis was investigated with Saccharomyces cerevisiae. Mutation frequencies and spectra were determined for an ung1 deletion strain in the target SUP4-o tRNA gene by using a forward selection scheme. Mutation frequencies in the SUP4-o gene increased about 20-fold relative to an isogenic wild-type S. cerevisiae strain, and the mutator effect was completely suppressed in the ung1 deletion strain carrying the wild-type UNG1 gene on a multicopy plasmid. Sixty-nine independently derived mutations in the SUP4-o gene were sequenced. All but five of these were due to GC----AT transitions. From this analysis, we conclude that the mutator phenotype of the ung1 deletion strain is the result of a failure to repair spontaneous cytosine deamination events occurring frequently in S. cerevisiae and that the UNG1 gene is not required for strand-specific mismatch repair in S. cerevisiae. PMID- 1938886 TI - The agmR gene, an environmentally responsive gene, complements defective glpR, which encodes the putative activator for glycerol metabolism in Pseudomonas aeruginosa. AB - The genes for the peripheral glycerol carbon metabolic pathway (glp) in Pseudomonas aeruginosa are postulated to be positively regulated by GlpR. A gene complementing the glpR2 allele, affecting expression of the putative activator, was cloned by a bacteriophage mini-D3112-based in vivo cloning method. Mini-D3112 replicons were isolated by transfecting glpR2 strain PRP406 and selecting clones able to grow on minimal medium containing glycerol as the sole carbon and energy source. Preliminary biochemical characterization indicated that the cloned activator gene for glycerol metabolism (agmR) may not be allelic to glpR. Restriction analysis and recloning of DNA fragments located the agmR gene to a 2.3-kb EcoRV-SstI DNA fragment. In a T7 RNA polymerase expression system, a single 26,000-Da protein was expressed from this DNA fragment. The amino acid sequence of this protein, deduced from the nucleotide sequence reported here, demonstrates its homology to the effector (or regulator) proteins of the environmentally responsive two-component regulators. The carboxy-terminal region of AgmR contains a possible helix-turn-helix DNA-binding motif and resembles sequences found in transcriptional regulators of the LuxR family. PMID- 1938888 TI - Molecular organization and nucleotide sequence of the recG locus of Escherichia coli K-12. AB - The nucleotide sequence of the Escherichia coli K-12 recG gene was determined. recG was identified as an open reading frame located between the spoT operon and the convergent gltS gene. It encodes a polypeptide of 693 amino acids which was identified as a 76-kDa protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after it was labeled with [35S]methionine in maxicells. The sequence determined revealed no obvious promoter. Synthesis of RecG by plasmids carrying the intact gene varied with the orientation of the insert relative to the vector promoter and with the extent of upstream spoT operon sequence included in the construction. It is concluded that recG is the fourth and last gene in the spoT operon, although a possible promoter for independent transcription of spoU and recG was identified near the end of the spoT gene. The primary sequence of RecG revealed that it is related to proteins that act as helicases and has a well conserved motif identified with ATP binding. PMID- 1938889 TI - Purification and characterization of Acinetobacter calcoaceticus isocitrate lyase. AB - Acinetobacter calcoaceticus is capable of growing on acetate or compounds that are metabolized to acetate. During adaptation to growth on acetate, A. calcoaceticus B4 exhibits an increase in NADP(+)-isocitrate dehydrogenase and isocitrate lyase activities. In contrast, during adaptation to growth on acetate, Escherichia coli exhibits a decrease in NADP(+)-isocitrate dehydrogenase activity that is caused by reversible phosphorylation of specific serine residues on this enzyme. Also, in E. coli, isocitrate lyase is believed to be active only in the phosphorylated form. This phosphorylation of isocitrate lyase may regulate entry of isocitrate into the glyoxylate bypass. To understand the relationships between these two isocitrate-metabolizing enzymes and the metabolism of acetate in A. calcoaceticus B4 better, we have purified isocitrate lyase to homogeneity. Physical and kinetic characterization of the enzyme as well as the inhibitor specificity and divalent cation requirement have been examined. PMID- 1938890 TI - Isolation from Candida albicans of a functional homolog of the Saccharomyces cerevisiae KRE1 gene, which is involved in cell wall beta-glucan synthesis. AB - The KRE1 gene of Saccharomyces cerevisiae, sacKRE1, appears to be involved in the synthesis of cell wall beta-glucan. S. cerevisiae strains with mutations in the KRE1 gene produce a structurally altered cell wall (1----6)-beta-glucan, which results in resistance to K1 killer toxin. We isolated the canKRE1 gene from Candida albicans by its ability to complement a kre1 mutation in S. cerevisiae and confer sensitivity to killer toxin. Sequence analysis revealed that the predicted protein encoded by canKRE1 shares an overall structural similarity with that encoded by sacKRE1. The canKRE1 protein is composed of an N-terminal signal sequence, a central domain of 46% identity with the sacKRE1 protein, and a C terminal hydrophobic tract. These structural and functional similarities imply that the canKRE1 gene carries out a function in C. albicans cell wall assembly similar to that observed for sacKRE1 in S. cerevisiae. PMID- 1938891 TI - Role of the S layer in morphogenesis and cell division of the archaebacterium Methanocorpusculum sinense. AB - Thin sections, freeze-etched, and negatively stained preparations of Methanocorpusculum sinense cells reveal a highly lobed cell structure with a hexagonally arranged surface layer (S layer). Digital image processing of negatively stained envelope fragments show that the S layer forms a porous but strongly interconnected network. Since the S layer is the exclusive cell envelope component outside the cytoplasmic membrane it must have a cell shape determining and maintaining function. Although lattice faults such as disclinations and dislocations are a geometrical necessity on the surface of a closed protein crystal, our data indicate that they also play important roles as sites for the incorporation of new morphological units, in the formation of the lobed cell structure, and in the cell division process. In freeze-etched preparations of intact cells numerous positive and negative 60 degree wedge disclinations can be detected which form pentagons and heptagons in the hexagonal array. Complementary pairs of pentagons and heptagons are the termination points of edge dislocations. They can be expected to function both as sites for incorporation of new morphological units into the lattice and as initiation points for the cell division process. The latter is determined by the ratio between the increase of protoplast volume and the increase in actual S-layer surface area during cell growth. We postulate that this mode of cell fission represents a common feature in lobed archaebacteria which possess an S layer as the exclusive wall component. PMID- 1938892 TI - Cloning and characterization of the gene for an additional extracellular serine protease of Bacillus subtilis. AB - We have purified a minor extracellular serine protease from a strain of Bacillus subtilis bearing null mutations in five extracellular protease genes: apr, npr, epr, bpr, and mpr (A. Sloma, C. Rudolph, G. Rufo, Jr., B. Sullivan, K. Theriault, D. Ally, and J. Pero, J. Bacteriol. 172:1024-1029, 1990). During purification, this novel protease (Vpr) was found bound in a complex in the void volume after gel filtration chromatography. The amino-terminal sequence of the purified protein was determined, and an oligonucleotide probe was constructed on the basis of the amino acid sequence. This probe was used to clone the structural gene (vpr) for this protease. The gene encodes a primary product of 806 amino acids. The amino acid sequence of the mature protein was preceded by a signal sequence of approximately 28 amino acids and a prosequence of approximately 132 amino acids. The mature protein has a predicted molecular weight of 68,197; however, the isolated protein has an apparent molecular weight of 28,500, suggesting that Vpr undergoes C-terminal processing or proteolysis. The vpr gene maps in the ctrA sacA-epr region of the chromosome and is not required for growth or sporulation. PMID- 1938893 TI - Salmonella acid shock proteins are required for the adaptive acid tolerance response. AB - Salmonella typhimurium, as well as other enteric bacteria, experiences significant fluctuations in H+ ion concentrations during growth in diverse ecological niches. In fact, some pH conditions which should kill cells rapidly, such as stomach acidity, are nevertheless tolerated. The complete mechanism for this tolerance is unknown. However, I have recently demonstrated that S. typhimurium has the ability to survive extreme low pH (pH 3.0 to 4.0) if first adapted to mild pH (pH 5.5 to 6.0). This phenomenon has been referred to as the acidification tolerance response (ATR). The exposure to mild acid is referred to as preshock, and the proteins involved are called preshock ATR proteins. A second type of encounter with acid, called acid shock, involves shifting cells directly from alkaline conditions (pH 7.7) to acid conditions (pH 4.5 or below). During acid shock, the organism immediately ceases reproduction and dramatically changes the expression of at least 52 proteins. All but four are distinct from the preshock ATR proteins. Surprisingly, acid shock alone did not afford significant protection against strong acid challenge in minimal medium. Furthermore, inhibiting protein synthesis prior to acid shock revealed that the acid shock proteins do not appear to contribute to acid survival in minimal medium even at pH 4.3. Constitutive cellular pH homeostatic mechanisms seem sufficient to protect cells at this pH. The data suggest that the induction of acid shock and preshock ATR proteins are separate processes requiring separate signals. However, for S. typhimurium to survive extreme acid conditions, it must induce both the preshock and acid shock systems. Preventing the expression of one or the other eliminates acid tolerance. I propose a two-stage process that allows S. typhimurium to phase in acid tolerance as the environmental pH becomes progressively more acidic. PMID- 1938894 TI - Mutations in the draT and draG genes of Rhodospirillum rubrum result in loss of regulation of nitrogenase by reversible ADP-ribosylation. AB - Reversible ADP-ribosylation of dinitrogenase reductase forms the basis of posttranslational regulation of nitrogenase activity in Rhodospirillum rubrum. This report describes the physiological effects of mutations in the genes encoding the enzymes that add and remove the ADP-ribosyl moiety. Mutants lacking a functional draT gene had no dinitrogenase reductase ADP-ribosyltransferase (DRAT, the draT gene product) activity in vitro and were incapable of modifying dinitrogenase reductase with ADP-ribose in vivo. Mutants lacking a functional draG gene had no dinitrogenase reductase-activating glycohydrolase (DRAG, the draG gene product) activity in vitro and were unable to remove ADP-ribose from the modified dinitrogenase reductase in vivo. Strains containing polar mutations in draT had no detectable DRAG activity in vitro, suggesting likely cotranscription of draT and draG. In strains containing draT and lacking a functional draG, dinitrogenase reductase accumulated in the active form under derepressing conditions but was rapidly ADP-ribosylated in response to conditions that cause inactivation. Detection of DRAT in these cells in vitro demonstrated that DRAT is itself subject to posttranslational regulation in vivo. Mutants affected in an open reading frame immediately downstream of draTG showed regulation of dinitrogenase reductase by ADP-ribosylation, although differences in the rates of ADP-ribosylation were apparent. PMID- 1938895 TI - A Bacteroides ruminicola 1,4-beta-D-endoglucanase is encoded in two reading frames. AB - Escherichia coli transformed with a plasmid containing a Bacteroides ruminicola endoglucanase (carboxymethyl cellulase [CMCase]) gene produced three immunologically cross-reacting CMCases which had molecular weights of 40,500, 84,000, and 88,000, while B. ruminicola produced CMCases with molecular weights of 82,000 and 88,000. The two B. ruminicola enzymes (purified from culture supernatants) had different N-terminal amino acid sequences, but each enzyme was encoded by the same gene (three independent clones had the same DNA sequence). The 88,000-molecular-weight CMCase (88K CMCase) gene appeared to contain two open reading frames which overlapped for 18 bp and were -1 out of frame, and each open reading frame contained several stop codons near the overlap region. The two 88K CMCase open reading frames had enough DNA to produce a protein of 106K, but the mobility of the enzyme in sodium dodecyl sulfate gels gave a value which was 20% lower. On the basis of the -1 frame shift and the large deviation in theoretical versus actual size, it appears that an unusual event (e.g., ribosomal hopping or RNA splicing) is involved in either the translation or the transcription of the 88K B. ruminicola CMCase gene. The 82K CMCase was completely encoded in the second reading frame, and its size was in agreement with the DNA sequence. PMID- 1938896 TI - Control of bacteriophage P2 gene expression: analysis of transcription of the ogr gene. AB - The bacteriophage P2 ogr gene encodes an 8.3-kDa protein that is a positive effector of P2 late gene transcription. The ogr gene is preceded by a promoter sequence (Pogr) resembling a normal Escherichia coli promoter and is located just downstream of a late transcription unit. We analyzed the kinetics and regulation of ogr gene transcription by using an ogr-specific antisense RNA probe in an S1 mapping assay. During a normal P2 infection, ogr gene transcription starts from Pogr at an intermediate time between the onset of early and late transcription. At late times after infection the ogr gene is cotranscribed with the late FETUD operon; the ogr gene product thus positively regulates its own synthesis from the P2 late promoter PF. Expression of the P2 late genes also requires P2 DNA replication. Complementation experiments and transcriptional analysis show that a nonreplicating P2 phage expresses the ogr gene from Pogr but is unable to transcribe the late genes. A P2 ogr-defective phage makes an increased level of ogr mRNA, consistent with autogenous control from Pogr. Transcription of the ogr gene in the prophage of a P2 heteroimmune lysogen is stimulated after infection with P2, suggesting that Pogr is under indirect immunity control and is activated by a yet-unidentified P2 early gene product during infection. PMID- 1938897 TI - Chemical and biological activities of a 64-kilodalton outer sheath protein from Treponema denticola strains. AB - This study examined the distribution of the major outer sheath proteins (MOSP) in several Treponema denticola strains and reports the isolation of a 64-kDa protein from the outer sheath of human clinical isolate T. denticola GM-1. The outer sheath was isolated by freeze-thaw procedures, and the distribution of outer sheath proteins was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). T. denticola GM-1, MS25, SR-5, and three low-passage clinical isolates possessed an MOSP with a relative molecular mass of 60 to 64 kDa. This MOSP was absent in T. denticola ATCC 35404 (TD-4) and clinical isolate SR-4. The latter possessed an MOSP of 58 kDa. 125I labeling revealed both MOSP to be dissociated forms of higher-molecular-mass oligomeric units between 116 and 162 kDa. Two-dimensional SDS-PAGE confirmed the modifiability of these MOSP. Isoelectric focusing of the 64-kDa MOSP indicated a pI of 6.7. Immunoblots with antiserum to GM-1 whole cells revealed the 64-kDa protein to be immunogenic and not cross-reactive with the MOSP of TD-4 or SR-4, and monospecific antibody to the 64-kDa protein recognized common epitopes on the high-molecular-weight oligomeric protein. These antibodies did not react with any component of TD-4 whole cells in immunoblots or in immunogold electron microscopy. Fab fragments inhibited the adherence of T. denticola GM-1 to human gingival fibroblasts by 78% (1:1,600; 0.72 micrograms of protein per ml), while TD-4 adherence was not inhibited. Amino acid analysis revealed a slightly acidic protein, devoid of cysteine, with 36% hydrophobic residues. Cyanogen bromide fragmentation of the 64 kDa protein revealed that a 42-kDa fragment contained a T-L-D-L-A-L-D segment which was 100% homologous with an integrin alpha subunit of a human leukocyte adhesion glycoprotein p 150,95. PMID- 1938898 TI - The product of the split sunY gene of bacteriophage T4 is a processed protein. AB - The sunY gene of bacteriophage T4 contains a self-splicing group I intron. The ligated exons encode an open reading frame of 605 amino acids, whose inferred molecular mass is 68 kDa. However, none of the proteins made following T4 infection have been assigned to the sunY gene, and no mutations have been mapped to this locus. We show here that the primary product of the sunY gene is a protein with an apparent molecular mass of 64 kDa, which is processed to a protein approximately 4 kDa smaller. Unlike most other processed T4 proteins, cleavage occurs independently of both the T4 processing protease, the product of gene 21, and late phage protein synthesis. Insertional mutagenesis demonstrated that the sunY protein is not necessary for normal T4 growth under the conditions tested. PMID- 1938899 TI - Five independent combinations of mutations can result in low-affinity penicillin binding protein 2x of Streptococcus pneumoniae. AB - Penicillin-binding protein 2x (PBP 2x) of Streptococcus pneumoniae is one of the high-molecular-weight PBPs involved in the development of intrinsic beta-lactam resistance. Point mutations in the PBP 2x genes (pbpX) have now been characterized in five independent spontaneous laboratory mutants in order to identify protein regions which are important for interaction with beta-lactam antibiotics. All mutant genes contained two to four mutations resulting in amino acid substitutions within the penicillin-binding domain of PBP 2x, and none of the mutants carried an identical set of mutations. For one particular mutant, C606, carrying four mutations in pbpX, the mutations at positions 601 and 597 conferred first- and second-level resistance when introduced into the susceptible parent strain S. pneumoniae R6. However, the other two mutations, at amino acid positions 289 and 422, which were originally selected at the fifth and sixth isolation steps, did not contribute at all to resistance in similar experiments. This suggests that they are phenotypically expressed only in combination with mutations in other genes. Three PBP 2x regions were mutated in from two to all four mutants carrying a low-affinity PBP 2x. However, in a fifth mutant containing a PBP 2x with apparent zero affinity for beta-lactams, the three mutations in pbpX mapped at entirely different positions. This demonstrates that different mutational pathways exist for remodeling this PBP during resistance development. PMID- 1938900 TI - Isolation and expression of a gene cluster responsible for biosynthesis of the glycopeptidolipid antigens of Mycobacterium avium. AB - Bacteria within the Mycobacterium avium complex are prominent in the environment and are a source of serious disseminated infections in patients with AIDS. Serovars of the M. avium complex are distinguished from all other mycobacteria and from one another by the presence of highly antigenic glycolipids, the glycopeptidolipids, on their surfaces. A genomic library of DNA from serovar 2 of the M. avium complex was constructed in the Escherichia coli-Mycobacterium shuttle cosmid, pYUB18, and used to clone and express in Mycobacterium smegmatis the genes responsible for the biosynthesis of the oligosaccharide segment of the M. avium serovar 2-specific glycopeptidolipid. The responsible gene cluster was mapped to a 22- to 27-kb functional region of the M. avium genome. The recombinant glycolipid was also isolated by high-pressure liquid chromatography and chemically characterized, by gas chromatography-mass spectrometry and fast atom bombardment-mass spectrometry, to demonstrate that the lipopeptide core originated in M. smegmatis, whereas the oligosaccharide segment arose from the cloned M. avium genes. This first-time demonstration of the cloning and expression, in a nonpathogenic mycobacterium, of the genes encoding complex cell wall glycoconjugates from a pathogenic mycobacterium presents a new approach for studying the role of such products in disease processes. PMID- 1938902 TI - A novel, highly efficient gene-cloning system for Micromonospora strains. AB - A highly efficient gene-cloning system for Micromonospora olivasterospora, a producer of the antibiotic fortimicin A (astromicin), suited to shotgun cloning has been developed. The system is supported by two new advancements accomplished in this study. One is the construction of novel plasmid vectors pMO116, pMO126, pMO133, pMO136, and pMO217, all consisting of replicons from newly found Micromonospora plasmids and selectable markers cloned from a neomycin-producing Micromonospora strain. The other advancement is the establishment of a new protocol for bacterial protoplasting in which some kinds of sugar alcohols are added in precultures. Such sugar alcohols were found to sensitize a wide taxonomical range of bacteria to lysozyme. The system is reproducible and reliable and has a high efficiency of more than 10(6) CFU/micrograms of DNA. PMID- 1938901 TI - Frameshifting in gene 10 of bacteriophage T7. AB - Gene 10 of bacteriophage T7, which encodes the most abundant capsid protein, has two products: a major product, 10A (36 kDa), and a minor product, 10B (41 kDa). 10B is produced by frameshifting into the -1 frame near the end of the 10A coding frame and is incorporated into the capsid. The frameshift occurs at a frequency of about 10% and is conserved in bacteriophage T3. This study shows that sequences important to frameshifting include the originally proposed frameshift site, consisting of overlapping phenylalanine codons and the 3' noncoding region that includes the transcriptional terminator over 200 bases downstream of the frameshift site. The frameshift occurs at the overlapping phenylalanine codons as determined from peptide sequencing data. Complementation studies show that there is only a very weak phenotype associated with phage infections in which there is no 10A frameshifting. Capsids from such infections are devoid of 10B and are as stable as wild-type capsids. PMID- 1938903 TI - Biochemical basis of mitochondrial acetaldehyde dismutation in Saccharomyces cerevisiae. AB - As reported previously, Saccharomyces cerevisiae cells deficient in all four known genes coding for alcohol dehydrogenases (ADH1 through ADH4) produce considerable amounts of ethanol during aerobic growth on glucose. It has been suggested that ethanol production in such adh0 cells is a corollary of acetaldehyde dismutation in mitochondria. This could be substantiated further by showing that mitochondrial ethanol formation requires functional electron transport, while the proton gradient or oxidative phosphorylation does not interfere with reduction of acetaldehyde in isolated mitochondria. This acetaldehyde-reducing activity is different from classical alcohol dehydrogenases in that it is associated with the inner mitochondrial membrane and also is unable to carry out ethanol oxidation. The putative cofactor is NADH + H+ generated by a soluble, matrix-located aldehyde dehydrogenase upon acetaldehyde oxidation to acetate. This enzyme has been purified from mitochondria of glucose-grown cells. It is clearly different from the known mitochondrial aldehyde dehydrogenase, which is absent in glucose-grown cells. Both acetaldehyde-reducing and acetaldehyde-oxidizing activities are also present in the mitochondrial fraction of fermentation-proficient (ADH+) cells. Mitochondrial acetaldehyde dismutation may have some significance in the removal of surplus acetaldehyde and in the formation of acetate in mitochondria during aerobic glucose fermentation. PMID- 1938904 TI - Use of 23Na nuclear magnetic resonance spectroscopy to determine the true intracellular concentration of free sodium in a halophilic eubacterium. AB - We present new data obtained by 23Na nuclear magnetic resonance spectroscopy, which can distinguish free intracellular sodium from cell-bound sodium, showing that the intracellular concentration of Na+ the halophilic eubacterium Vibrio costicola is only 5 to 20% of that in the extracellular medium. Previous methods could not distinguish free intracellular Na+ from that bound to cell structures, and it was believed that in halophilic eubacteria the total monovalent cation concentration inside matched that of the NaCl outside. Information obtained by the newer technology raises fundamental questions about the ways in which these organisms and others which live in hypersaline environments function and cope with osmotic stress. PMID- 1938905 TI - Fragments of the internal transcribed spacer 1 of pre-rRNA accumulate in Saccharomyces cerevisiae lacking 5'----3' exoribonuclease 1. AB - The portion of the internal transcribed spacer 1 found on 20S pre-rRNA accumulates in Saccharomyces cerevisiae lacking 5'----3' exoribonuclease 1, showing that an endonucleolytic cleavage at the 3' terminus of 18S rRNA is involved in the 20S pre-rRNA to 18S mature rRNA conversion. Smaller fragments of the spacer sequence are also found. The exoribonuclease may be involved as a cytoplasmic RNase in the hydrolysis of the spacer. PMID- 1938906 TI - Evidence for interactions between MotA and MotB, torque-generating elements of the flagellar motor of Escherichia coli. AB - Cells that overexpress MotA (encoded on a plasmid derived from pBR322) grow slowly because of proton leakage. We have traced this defect to the coexpression of a fusion protein consisting of 60 amino acids from the N terminus of MotB and 50 amino acids specified by pBR322. Mutations within the N terminus, known to abolish function when present in full-length MotB, reversed the growth defect. Growth also was normal when MotA was coexpressed with wild-type MotB or with a series of MotB N-terminal fragments. PMID- 1938907 TI - Nucleotide sequence and expression analysis of the Acetobacter xylinum uridine diphosphoglucose pyrophosphorylase gene. AB - The nucleotide sequence of the Acetobacter xylinum uridine diphosphoglucose pyrophosphorylase gene was determined; this is the first procaryotic uridine diphosphoglucose pyrophosphorylase gene sequence reported. The sequence data indicated that the gene product consists of 284 amino acids. This finding was consistent with the results obtained by expression analysis in vivo and in vitro in Escherichia coli. PMID- 1938908 TI - Purification and N-terminal amino acid sequences of Chlamydia trachomatis histone analogs. AB - DNA-binding proteins specific to Chlamydia trachomatis elementary bodies have been described and recently characterized as procaryotic histone analogs. I have developed an affinity purification procedure for the 18-kDa histone analog, Hc1, based on its affinity for polyanions. The availability of highly purified Hc1 has allowed for determination of its N-terminal amino acid sequence and should prove useful in studies of its biological function. The variable C. trachomatis histone analog not obtained by this procedure was electrophoresed onto Immobilon paper for sequencing. The N terminus of the variable histone was conserved among C. trachomatis serotypes L2, D, and B and was distinct from that of Hc1. PMID- 1938909 TI - Arrangement of nitrogenase structural genes in an aerobic filamentous nonheterocystous cyanobacterium. AB - Members of the marine filamentous, nonheterocystous cyanobacterial genus Trichodesmium not only are capable of fixing nitrogen aerobically in the light but when grown under a light-dark cycle will fix nitrogen only during the light phase. In this study, we constructed a restriction map of the structural nitrogen fixation genes (nifHDK) in Trichodesmium sp. strain NIBB 1067. We found that the organization of the nif genes in Trichodesmium sp. strain NIBB 1067 is contiguous, as found in other nonheterocystous cyanobacteria and in heterocysts. Furthermore, the nif gene arrangement was identical when the cultures were grown with combined nitrogen or under nitrogen-fixing conditions. Therefore, no gene rearrangements occur, such as those that occur during the development of heterocysts in heterocystous species. PMID- 1938911 TI - Independent regulation of nifHDK operon transcription and DNA rearrangement during heterocyst differentiation in the cyanobacterium Anabaena sp. strain PCC 7120. AB - The filamentous cyanobacterium Anabaena sp. strain PCC 7120 expresses the genes required for nitrogen fixation in terminally differentiated cells called heterocysts. The nifHDK operon encodes the nitrogenase polypeptides and is expressed at high levels in heterocysts. During heterocyst differentiation, an 11 kb DNA element is excised from the nifD gene by site-specific recombination. The xisA gene, located on the 11-kb element, is required for the excision of the element. Transcription and DNA rearrangement of the nifHDK operon both occur late during heterocyst differentiation, about 18 to 24 h after induction, suggesting that the regulation of these events might be coupled. We show that heterocyst specific transcription and DNA rearrangement of the nifHDK operon are independent of one another. Northern (RNA) analysis of the xisA mutant strain DW12-2.2, which cannot excise the nifD 11-kb element or fix nitrogen, showed that the nifH and nifD genes are transcribed on unrearranged chromosomes. The nifK gene was not transcribed in DW12-2.2, indicating that its expression is dependent on the nifH promoter and excision of the 11-kb element from the operon. A 1.68-kb DNA fragment containing the nifH promoter was deleted from the chromosome to produce the mutant strain LW1. LW1 formed heterocysts but did not grow on nitrogen-free medium and showed no transcription through nifD. Southern analysis of LW1 showed normal excision of the 11-kb element from the nifHDK operon, indicating that transcription from the nifH promoter is not required for the developmentally regulated DNA rearrangement. PMID- 1938910 TI - Atypical lipoteichoic acids of gram-positive bacteria. PMID- 1938912 TI - Purification and characterization of a soybean flour-inducible ferredoxin reductase of Streptomyces griseus. AB - We have purified an NADH-dependent ferredoxin reductase from crude extracts of Streptomyces griseus cells grown in soybean flour-enriched medium. The purified protein has a molecular weight of 60,000 as determined by sodium dodecyl sulfate gel electrophoresis. The enzyme requires Mg2+ ion for catalytic activity in reconstituted assays, and its spectral properties resemble those of many other flavin adenine dinucleotide-containing flavoproteins. A relatively large number of hydrophobic amino acid residues are found by amino acid analysis, and beginning with residue 7, a consensus flavin adenine dinucleotide binding sequence, GXGXXGXXXA, is revealed in this protein. In the presence of NADH, the ferredoxin reductase reduces various electron acceptors such as cytochrome c, potassium ferricyanide, dichlorophenolindophenol, and nitroblue tetrazolium. However, only cytochrome c reduction by the ferredoxin reductase is enhanced by the addition of ferredoxin. In the presence of NADH, S. griseus ferredoxin and cytochrome P-450soy, the ferredoxin reductase mediates O dealkylation of 7 ethoxycoumarin. PMID- 1938914 TI - Expression of the avirulence gene avrBs3 from Xanthomonas campestris pv. vesicatoria is not under the control of hrp genes and is independent of plant factors. AB - The avirulence gene avrBs3 from Xanthomonas campestris pv. vesicatoria pepper race 1 is responsible for the induction of a race-specific hypersensitive reaction in resistant pepper cultivars. A DNA region of 3.7 kb, containing several open reading frames and an internal repetitive region, was shown previously to be necessary for avirulence activity (U. Bonas, R. E. Stall, and B. Staskawicz, Mol. Gen. Genet. 218:127-136, 1989). The promoter of avrBs3 was identified by using gene fusions to beta-glucuronidase. Also, we mapped the transcription start site and showed that the avrBs3 gene is expressed constitutively in cells grown in minimal or complex medium and in planta. Polyclonal antibodies raised against a fusion protein produced in Escherichia coli allowed the identification of a 122-kDa protein in X. campestris pv. vesicatoria cells expressing the avrBs3 gene. The antibody is specific for AvrBs3 in X. campestris pv. vesicatoria cells but also recognizes homologous proteins in other pathovars of X. campestris. We found that AvrBs3 is localized intracellularly in X. campestris pv. vesicatoria and is mainly in the soluble fraction. The effect of mutations in the hrp gene cluster on the function of AvrBs3 was examined. Expression of AvrBs3 in X. campestris pv. vesicatoria grown in minimal or complex medium is independent of the hrp gene cluster that determines pathogenicity and hypersensitivity to X. campestris pv. vesicatoria. In the plant, however, the hrp genes are required for elicitation of a race specific resistance response. PMID- 1938913 TI - Multiple domains in endoglucanase B (CenB) from Cellulomonas fimi: functions and relatedness to domains in other polypeptides. AB - Endoglucanase B (CenB) from the bacterium Cellulomonas fimi is divided into five discrete domains by linker sequences rich in proline and hydroxyamino acids (A. Meinke, C. Braun, N. R. Gilkes, D. G. Kilburn, R. C. Miller, Jr., and R. A. J. Warren, J. Bacteriol. 173:308-314, 1991). The catalytic domain of 608 amino acids is at the N terminus. The sequence of the first 477 amino acids in the catalytic domain is related to the sequences of cellulases in family E, which includes procaryotic and eucaryotic enzymes. The sequence of the last 131 amino acids of the catalytic domain is related to sequences present in a number of cellulases from different families. The catalytic domain alone can bind to cellulose, and this binding is mediated at least in part by the C-terminal 131 amino acids. Deletion of these 131 amino acids reduces but does not eliminate activity. The catalytic domain is followed by three domains which are repeats of a 98-amino acid sequence. The repeats are approximately 50% identical to two repeats of 95 amino acids in a chitinase from Bacillus circulans which are related to fibronectin type III repeats (T. Watanabe, K. Suzuki, K. Oyanagi, K. Ohnishi, and H. Tanaka, J. Biol. Chem. 265:15659-15665, 1990). The C-terminal domain of 101 amino acids is related to sequences, present in a number of bacterial cellulases and xylanases from different families, which form cellulose-binding domains (CBDs). It functions as a CBD when fused to a heterologous polypeptide. Cells of Escherichia coli expressing the wild-type cenB gene accumulate both native CenB and a stable proteolytic fragment of 41 kDa comprising the three repeats and the C-terminal CBD. The 41-kDa polypeptide binds to cellulose but lacks enzymatic activity. PMID- 1938915 TI - Effects of glucosamine on lysis, glycerol formation, and sporulation in Myxococcus xanthus. AB - Glucosamine (GlcN), which has previously been shown to rescue fruiting body formation, lysis, and sporulation in a developmental mutant (G. Janssen and M. Dworkin, Dev. Biol. 112:194-202, 1985), induced lysis in vegetative and developing wild-type cells and inhibited fruiting body formation. It also resulted in a transient, intracellular increase in the concentration of glycerol, a known sporulation inducer, and sporulation of the surviving cells. Phospholipase activity, which was shown to be normally developmentally regulated, increased 7.6-fold after treatment of vegetative cells with 50 mM GlcN. Likewise, autocidal activity, which normally increased 18 to 24 h after the initiation of development, increased 20% when vegetative or developing cells were exposed to GlcN. Two mutants resistant to GlcN-induced lysis (MD1021 and MD1022) were isolated and showed neither an increase in autocide production nor an increase in phospholipase activity in response to added GlcN. MD1021 was developmentally deficient, and GlcN rescued fruiting body formation as well as phospholipase activity and autocide production. We propose that GlcN exerts its lytic effect by regulating the activity of phospholipase enzymes that release autocides, compounds that are believed to be responsible for developmental autolysis. GlcN induced sporulation was found to depend on several factors: the initial cell density, the amount of lysis induced by GlcN, and the presence of tan-phase variants. An initial cell density of greater than 2 x 10(5) cells per ml was required to support GlcN-induced sporulation, and sporulation did not occur unless 50 to 75% of these cells had lysed. Mutants that were resistant to GlcN induced lysis also did not sporulate in the presence of GlcN. The effects of GlcN on developing cells depended on the concentration of GlcN added; the addition of low concentrations of GlcN resulted in enhancement of sporulation, while higher concentrations resulted in the inhibition of sporulation. The ultrastructure of GlcN-induced spores resembled that of spores induced by the exogenous addition of glycerol, in contrast to spores isolated from mature fruiting bodies. A model by which GlcN may regulate both lysis and sporulation is presented. PMID- 1938916 TI - Upstream induction sequence, the cis-acting element required for response to the allantoin pathway inducer and enhancement of operation of the nitrogen-regulated upstream activation sequence in Saccharomyces cerevisiae. AB - Expression of the DAL2, DAL4, DAL7, DUR1,2, and DUR3 genes in Saccharomyces cerevisiae is induced by the presence of allophanate, the last intermediate of the allantoin degradative pathway. Analysis of the DAL7 5'-flanking region identified an element, designated the DAL upstream induction sequence (DAL UIS), required for response to inducer. The operation of this cis-acting element requires functional DAL81 and DAL82 gene products. We determined the DAL UIS structure by using saturation mutagenesis. A specific dodecanucleotide sequence is the minimum required for response of reporter gene transcription to inducer. There are two copies of the sequence in the 5'-flanking region of the DAL7 gene. There are one or more copies of the sequence upstream of each allantoin pathway gene that responds to inducer. The sequence is also found 5' of the allophanate inducible CAR2 gene as well. No such sequences were detected upstream of allantoin pathway genes that do not respond to the presence of inducer. We also demonstrated that the presence of a UIS element adjacent to the nitrogen regulated upstream activation sequence significantly enhances its operation. PMID- 1938917 TI - Mismatch repair genes of Streptococcus pneumoniae: HexA confers a mutator phenotype in Escherichia coli by negative complementation. AB - DNA repair systems able to correct base pair mismatches within newly replicated DNA or within heteroduplex molecules produced during recombination are widespread among living organisms. Evidence that such generalized mismatch repair systems evolved from a common ancestor is particularly strong for two of them, the Hex system of the gram-positive Streptococcus pneumoniae and the Mut system of the gram-negative Escherichia coli and Salmonella typhimurium. The homology existing between HexA and MutS and between HexB and MutL prompted us to investigate the effect of expressing hex genes in E. coli. Complementation of mutS or mutL mutations, which confer a mutator phenotype, was assayed by introducing on a multicopy plasmid the hexA and hexB genes, under the control of an inducible promoter, either individually or together in E. coli strains. No decrease in mutation rate was conferred by either hexA or hexB gene expression. However, a negative complementation effect was observed in wild-type E. coli cells: expression of hexA resulted in a typical Mut- mutator phenotype. hexB gene expression did not increase the mutation rate either individually or in conjunction with hexA. Since expression of hexA did not affect the mutation rate in mutS mutant cells and the hexA-induced mutator effect was recA independent, it is concluded that this effect results from inhibition of the Mut system. We suggest that HexA, like its homolog MutS, binds to mismatches resulting from replication errors, but in doing so it protects them from repair by the Mut system. In agreement with this hypothesis, an increase in mutS gene copy number abolished the hexA-induced mutator phenotype. HexA protein could prevent repair either by being unable to interact with Mut proteins or by producing nonfunctional repair complexes. PMID- 1938918 TI - Linear plasmids of Borrelia burgdorferi have a telomeric structure and sequence similar to those of a eukaryotic virus. AB - Spirochetes of the genus Borrelia have double-stranded linear plasmids with covalently closed ends. The physical nature of the terminal connections was determined for the 16-kb linear plasmid of the B31 strain of the Lyme disease agent Borrelia burgdorferi. Native telomeric fragments representing the left and right ends of this plasmid were isolated and subjected to Maxam-Gilbert sequence analysis. At the plasmid ends the two DNA strands formed an uninterrupted, perfectly palindromic, AT-rich sequence. This Borrelia linear plasmid consisted of a continuous polynucleotide chain that is fully base paired except for short single-stranded hairpin loops at each end. The left and right telomeres of the 16 kb plasmid were identical for 16 of the first 19 nucleotide positions and constituted an inverted terminal repeat with respect to each other. The left telomere of the 49-kb plasmid of strain B31 was identical to the corresponding telomere of the 16-kb plasmid. Different-sized plasmids of other strains of B. burgdorferi also contained sequences homologous to the left end of the 16-kb plasmid. When the borrelia telomeres were compared with telomeric sequences of other linear double-stranded DNA replicons, sequence similarities were noted with poxviruses and particularly with the iridovirus agent of African swine fever. The latter virus and a Borrelia sp. share the same tick vector. These findings suggest that the novel linear plasmids of Borrelia originated through a horizontal genetic transfer across kingdoms. PMID- 1938920 TI - Recombination in Escherichia coli and the definition of biological species. AB - The DNA sequence of part of the gnd (6-phosphogluconate dehydrogenase) gene was determined for eight wild strains of Escherichia coli and for Salmonella typhimurium. Since a region of the trp (tryptophan) operon and the phoA (alkaline phosphatase) gene have been sequenced from the same strains, the gene trees for these three regions were determined and compared. Gene trees are different from species or strain trees in that a gene tree is derived from a particular segment of DNA, whereas a species or strain tree should be derived from many such segments and is the tree that best represents the phylogenetic relationship of the species or strains. If there were no recombination in E. coli, the gene trees for different genes would not be statistically different from the strain tree or from each other. But, if the gene trees are significantly different, there must have been recombination. Methods are proposed that show these gene trees to be statistically different. Since the gene trees are different, we conclude that recombination is important in natural populations of E. coli. Finally, we suggest that gene trees can be used to create an operational means of defining bacterial species by using the biological species definition. PMID- 1938919 TI - Formation in vitro of complexes between an abnormal fusion protein and the heat shock proteins from Escherichia coli and yeast mitochondria. AB - Heat shock proteins (HSPs) of the Hsp70 and GroEL families associate with a variety of cell proteins in vivo. However, the formation of such complexes has not been systematically studied. A 31-kDa fusion protein (CRAG), which contains 12 residues of cro repressor, truncated protein A, and 14 residues of beta galactosidase, when expressed in Escherichia coli, was found in complexes with DnaK, GrpE, protease La, and GroEL. When an E. coli extract not containing CRAG was applied to an affinity column containing CRAG, DnaK, GroEL, and GrpE were selectively bound. These HSPs did not bind to a normal protein A column. DnaK, GrpE, and the fraction of GroEL could be eluted from the CRAG column with ATP but not with a nonhydrolyzable ATP analog. The ATP-dependent release of DnaK and GroEL also required Mg2+, but GrpE dissociated with ATP alone. The binding and release of DnaK and GroEL were independent events, but the binding of GrpE required DnaK. Inactivation of DnaJ, GrpE, and GroES did not affect the association or dissociation of DnaK or GroEL from CRAG. The DnaK and GrpE proteins could be eluted with 10(-6) M ATP, but 10(-4) M was required for GroEL release. This approach allows a one-step purification of these proteins from E. coli and also the isolation of the DnaK and GroEL homologs from yeast mitochondria. Competition experiments with oligopeptide fragments of CRAG showed that DnaK and GroEL interact with different sites on CRAG and that the cro derived domain of CRAG contains the DnaK-binding site. PMID- 1938922 TI - Growth stage signal transduction and the requirements for srfA induction in development of competence. AB - srfA is an operon needed for the development of genetic competence in Bacillus subtilis. This operon is normally expressed at a low level during growth, and its transcription increases sharply just before the transition to stationary phase. The genetic requirements for the full expression of srfA were previously examined in several laboratories and shown to include spo0A, spo0H, spo0K, comQ, and comA. In the present study these results were confirmed with an isogenic set of strains. We have also shown that comP is needed for srfA expression but that other regulatory genes required for competence (degU, sin, and abrB) are not needed for the expression of srfA. We have used the expression of srfA under control of the regulatable Pspac promoter to study the kinetics of competence development and to determine whether the genes ordinarily required for expression of srfA are needed for any additional roles during the development of competence. When expression of srfA was driven from Pspac, competence was expressed constitutively throughout growth. Furthermore, when srfA was expressed from Pspac, the spo0K, comQ, comP, and comA determinants were no longer required for the expression of competence. We conclude therefore that the multiple signals which trigger the initiation of competence development in relation to growth stage are ordinarily received prior to the increase in srfA expression. We propose that these signals are mediated by the products of spo0K, comQ, comP, and comA, resulting in the phosphorylation of ComA by ComP. This in turn would enable ComA to function as a positive transcription factor for srfA, leading to the elaboration of the srfA product(s) and the consequent initiation of competence. We also propose that this is the major, and possibly the only, role for the spo0K, comQ, comP, and comA products during competence development. PMID- 1938921 TI - The primary role of comA in establishment of the competent state in Bacillus subtilis is to activate expression of srfA. AB - The establishment of genetic competence in Bacillus subtilis requires the genes of the competence regulon which function in the binding, processing, and transport of DNA. Their expression is governed by multiple regulatory pathways that are composed of the comA, comP, sin, abrB, spo0H, spo0K, spo0A, degU, and srfA gene products. Among these, srfA is thought to occupy an intermediate position in one of the pathways that controls late competence gene expression. The full expression of srfA requires the gene products of comP, comA, and spo0K. To determine the role of these genes in the regulation of competence development, the expression of the srfA operon was placed under control of the isopropyl-beta D-thiogalactopyranoside (IPTG)-inducible promoter Pspac and the expression of the Pspac-srfA construct was examined in mutants blocked in early competence. By monitoring the IPTG-induced expression of Pspac-srfA with a srfA-lacZ operon fusion, it was observed that srfA expression was no longer dependent on the products of comP, comA, and spo0K. Production of the lipopeptide antibiotic surfactin in Pspac-srfA-bearing cells was induced in the presence of IPTG and was independent of ComP and ComA. Competence development was induced by IPTG and was independent of comP, comA, and spo0K in cells carrying Pspac-srfA. These results suggest that the ComP-ComA signal transduction pathway as well as Spo0K is required for the expression of srfA in the regulatory cascade of competence development. Studies of Pspac-srfA also examined the involvement of srfA in the growth stage-specific and nutritional regulation of a late competence gene. PMID- 1938923 TI - The cell cycle-regulated flagellar gene flbF of Caulobacter crescentus is homologous to a virulence locus (lcrD) of Yersinia pestis. AB - We have characterized flbF, a key locus located at the top of the flagellar gene hierarchy of Caulobacter crescentus. This gene is required for transcription from sigma 54 promoters of fla genes expressed late in the cell cycle. We have determined the nucleotide sequence of the gene, mapped the 5' end of the flbF RNA, and examined the pattern of expression in the cell cycle. Our results show that flbF is expressed earlier in the cell cycle than other fla genes, that it is expressed at a low level throughout the stalked cell cycle, and that its 5' regulatory region contains sequences that can be aligned with the sigma 28 promoter consensus reported for enteric bacteria. flbF contains an open reading frame of 700 residues with an amino-terminal half rich in hydrophobic residues that could correspond to six to eight transmembrane domains. The translated flbF sequence is very similar to LcrD (low calcium response) encoded by virulence plasmids of pathogenic Yersinia spp. (G. Plano, S. Barve, and S. Straley, J. Bacteriol. 173:7293-7303, 1991). LcrD and FlbF can be aligned over the entire length of the proteins with the greatest degree of sequence identity (45%) in the hydrophobic amino-terminal region. The high degree of sequence homology of proteins derived from widely differing organisms, including Caulobacter and Yersinia species, suggests that FlbF and LcrD may be representatives of a larger family of regulatory proteins with a common sensor mechanism for modifying responses to appropriate stimuli. PMID- 1938924 TI - Physiological sources of reductant for nitrogen fixation activity in Nostoc sp. strain UCD 7801 in symbiotic association with Anthoceros punctatus. AB - Pure cultures of the symbiotic cyanobacterium-bryophyte association with Anthoceros punctatus were reconstituted by using Nostoc sp. strain UCD 7801 or its 3-(3,4-dichlorophenol)-1,1-dimethylurea (DCMU)-resistant mutant strain, UCD 218. The cultures were grown under high light intensity with CO2 as the sole carbon source and then incubated in the dark to deplete endogenous reductant pools before measurements of nitrogenase activities (acetylene reduction). High rates of light-dependent acetylene reduction were obtained both before starvation in the dark and after recovery from starvation, regardless of which of the two Nostoc strains was reconstituted in the association. Rates of acetylene reduction by symbiotic tissue with the wild-type Nostoc strain decreased 99 and 96% after 28 h of incubation in the dark and after reexposure to light in the presence of 5 microM DCMU, respectively. Supplementation of the medium with glucose restored nitrogenase activity in the dark to a rate that was 64% of the illuminated rate. In the light and in the presence of 5 microM DCMU, acetylene reduction could be restored to 91% of the uninhibited rate by the exogenous presence of various carbohydrates. The rate of acetylene reduction in the presence of DCMU was 34% of the uninhibited rate of tissue in association with the DCMU-resistant strain UCD 218. This result implies that photosynthates produced immediately by the cyanobacterium can supply at least one-third of the reductant required for nitrogenase activity on a short-term basis in the symbiotic association. However, high steady-state rates of nitrogenase activity by symbiotic Nostoc strains appear to depend on endogenous carbohydrate reserves, which are presumably supplied as photosynthate from both A. punctatus tissue and the Nostoc strain. PMID- 1938925 TI - Identification of the DNA region responsible for sulfur-oxidizing ability of Thiosphaera pantotropha. AB - For the identification of the DNA region responsible for the sulfur-oxidizing ability (Sox) of Thiosphaera pantotropha, we used previously isolated Tn5-mob insertional Sox- mutants. For seven mutants, the Tn5-mob insertion was localized on the chromosome rather than on the megaplasmids pHG41 or pHG42 by using the Tn5 mob-harboring vehicle pSUP5011 as probe. The specific insertion of Tn5-mob into a sox gene was determined for one Sox- mutant, strain TP19. An 18-kb EcoRI fragment was cloned in Escherichia coli by using the mobilizable plasmid pSUP202 as vector and the kanamycin resistance gene of Tn5 as marker. Conjugal transfer of the resulting hybrid plasmid, pKS3-13, to the wild type resulted in two phenotypically different groups of recombinants. Ninety-five percent of the recombinants were Sox+, kanamycin resistant, and tetracycline resistant; 5% were homogenote recombinants exhibiting the Sox-, kanamycin-resistant, tetracycline sensitive phenotype, and these indicated the specific insertion. To isolate the respective wild-type sox gene, total DNA from a heterogenote recombinant was partially restricted with EcoRI, religated, and transformed in E. coli. Transformants carrying a pSUP202-derived hybrid plasmid with the intact sox gene were identified by screening for a tetracycline-resistant, kanamycin-sensitive, and chloramphenicol-sensitive phenotype and by complementation of the Sox- mutant TP19. A plasmid of this type, pEG12, contained an insert of 13 kb which gave a positive signal in Southern hybridization with the homologous probe of pKS3-13. pEG12 was used to determine the DNA homology of the sulfur-oxidizing enzyme systems of other thiobacteria. Strong hybridization signals were obtained with total DNA of the neutrophilic sulfur-oxidizing bacteria Paracoccus denitrificans, Thiobacillus versutus, and Rhodobacter capsulatus. No hybridization signal was obtained with DNA of other neutrophilic or acidophilic thiobacteria examined. PMID- 1938927 TI - Cloning and structural characterization of the mcrA locus of Escherichia coli. AB - Escherichia coli has DNA restriction systems which are able to recognize and attack modified cytosine residues in the DNA of incoming bacteriophages and plasmids. The locus for the McrA/RglA system of modified cytosine restriction was located near the pin gene of the defective element, e14. Hence, loss of the e14 element through abortive induction after UV irradiation caused a permanent loss of McrA restriction activity. e14 DNA encoding McrA restriction was cloned and sequenced to reveal a single open reading frame of 831 bp with a predicted gene product of 31 kDa. Clones expressing the complete open reading frame conferred both McrA and RglA phenotypes; however, a deletion derivative was found which complemented RglA restriction against nonglucosylated T6gt phage but did not complement for McrA restriction of methylated plasmid DNA. Possible explanations for this activity and a comparison with the different organization of the McrB/RglB restriction system are discussed. PMID- 1938928 TI - Conversion of Bacillus subtilis 168 to a subtilin producer by competence transformation. AB - Subtilin is a ribosomally synthesized peptide antibiotic produced by Bacillus subtilis ATCC 6633. B. subtilis 168 was converted to a subtilin producer by competence transformation with chromosomal DNA from B. subtilis ATCC 6633. A chloramphenicol acetyltransferase gene was inserted next to the subtilin structural gene as a selectable marker. The genes that conferred subtilin production were derived from a 40-kb region of the B. subtilis ATCC 6633 chromosome that had flanking homologies to the B. subtilis 168 chromosome. The subtilin produced by the mutant was identical to natural subtilin in its biological activity, chromatographic behavior, amino acid composition, and N terminal amino acid sequence. PMID- 1938926 TI - One-step cloning system for isolation of bacterial lexA-like genes. AB - A system to isolate lexA-like genes of bacteria directly was developed. It is based upon the fact that the presence of a lexA(Def) mutation is lethal to SulA+ cells of Escherichia coli. This system is composed of a SulA- LexA(Def) HsdR- strain and a lexA-conditional killer vector (plasmid pUA165) carrying the wild type sulA gene of E. coli and a polylinker in which foreign DNA may be inserted. By using this method, the lexA-like genes of Salmonella typhimurium, Erwinia carotovora, Pseudomonas aeruginosa, and P. putida were cloned. We also found that the LexA repressor of S. typhimurium presented the highest affinity for the SOS boxes of E. coli in vivo, whereas the LexA protein of P. aeruginosa had the lowest. Likewise, all of these LexA repressors were cleaved by the activated RecA protein of E. coli after DNA damage. Furthermore, under high-stringency conditions, the lexA gene of E. coli hybridized with the lexA genes of S. typhimurium and E. carotovora but not with those of P. aeruginosa and P. putida. PMID- 1938929 TI - Induction of the second exopolysaccharide (EPSb) in Rhizobium meliloti SU47 by low phosphate concentrations. AB - In previous work, Rhizobium meliloti SU47 produced its alternative exopolysaccharide (EPSb [also called EPS II]) only in strains that were genetically altered to activate EPSb synthesis. Here we report that EPSb synthesis is not entirely cryptic but occurred under conditions of limiting phosphate. This was shown in several different exo mutants that are blocked in the synthesis of the normal exopolysaccharide, succinoglycan. In addition, EPSb biosynthetic gene expression was markedly increased by limiting phosphate. An apparent regulatory mutant that does not express alkaline phosphatase activity was unable to produce EPSb under these conditions. A mucR mutant that was previously shown to produce EPSb instead of the normal exopolysaccharide, succinoglycan, was not sensitive to phosphate inhibition of EPSb synthesis. No evidence was found to indicate that exoX, which affects succinoglycan synthesis, had any influence on EPSb synthesis. In contrast to limiting phosphate, limiting nitrogen or sulfur did not stimulate EPSb synthesis as it does succinoglycan. PMID- 1938931 TI - Differential response of the bvg virulence regulon of Bordetella pertussis to MgSO4 modulation. AB - Magnesium sulfate is known to repress the expression of the virulence factors of Bordetella pertussis that are coordinately regulated by the bvg locus. We have tested the time required by MgSO4 to repress the synthesis of several bvg regulated mRNA species and found that the promoters of the virulence genes (pertussis toxin, adenylate cyclase, and filamentous hemagglutinin) are repressed in 6 min, while the autogenously regulated promoters of the bvg locus (P1, P3, and P4) are repressed only several hours later. These data show a differential behavior between regulated and autoregulated genes of the bvg regulon. PMID- 1938932 TI - Location of the fadBA operon on the physical map of Escherichia coli. PMID- 1938933 TI - Locations of the genes from pepD through proA on the physical map of the Escherichia coli chromosome. PMID- 1938930 TI - Absence of hisT-mediated tRNA pseudouridylation results in a uracil requirement that interferes with Escherichia coli K-12 cell division. AB - We show that hisT function is required for normal growth of Escherichia coli K 12, since a lack of hisT-mediated pseudouridine tRNA modification causes a uracil requirement that interferes with cell division. We also show that hisT transcription is positively growth rate regulated in exponentially growing bacteria and is induced during the transition from exponential to stationary growth phase. PMID- 1938934 TI - Location of pinO, a new gene located between tufA and rpsJ, on the physical map of the Escherichia coli chromosome. PMID- 1938935 TI - Physical maps of the rfa loci of Escherichia coli K-12 and Salmonella typhimurium. PMID- 1938936 TI - Locations and orientations on the Escherichia coli physical map of the mgl operon and galS, a new locus for galactose ultrainduction. PMID- 1938937 TI - The Escherichia coli fdv gene probably encodes mutS and is located at minute 58.8 adjacent to the hyc-hyp gene cluster. PMID- 1938938 TI - Molecular cloning of the extracellular endodextranase of Streptococcus salivarius. AB - We report the cloning in Escherichia coli of the gene encoding an extracellular endodextranase (alpha-1,6-glucanhydrolase, EC 3.2.1.11) from Streptococcus salivarius PC-1. Recombinants from a S. salivarius PC-1-Lambda ZAP II genomic library specifying dextranase activity were identified as plaques surrounded by zones of clearing on blue dextran agar. One such clone, PD1, had a 6.3-kb EcoRI fragment insert which encoded a 190-kDa protein with dextranase activity. The recombinant strain also produced two lower-molecular-mass polypeptides (90 and 70 kDa) that had dextranase activity. Native dextranase was recovered from concentrated culture fluids of S. salivarius as a single 110-kDa polypeptide. PD1 phage lysate and PC-1 culture supernatant fluid extract were used to measure substrate specificity of the recombinant and native forms of dextranase, respectively. Analysis of these reaction products by thin-layer chromatography revealed the expected isomaltosaccharide products yielded by the recombinant specified enzyme but was unable to resolve the larger polysaccharide products of the native enzyme. Furthermore, S. salivarius utilized neither the substrates nor the products of dextran hydrolysis for growth. PMID- 1938939 TI - The yeast heat shock response is induced by conversion of cells to spheroplasts and by potent transcriptional inhibitors. AB - We report here that procedures commonly used to measure transcription and mRNA decay rates in Saccharomyces cerevisiae induce the heat shock response. First, conversion of cells to spheroplasts with lyticase, a prerequisite for nuclear runoff transcription, induces the expression of HSP70 and HSP90 heat shock genes. The transcript levels of the non-heat-shock gene ACT1 are slightly depressed, consistent with the general yeast stress response. Second, the DNA intercalator, 1,10-phenanthroline, widely employed as a general transcriptional inhibitor in S. cerevisiae, enhances the mRNA abundance of certain heat shock genes (HSP82, SSA1 SSA2) although not of others (HSC82, SSA4, HSP26). Third, the antibiotic thiolutin, previously demonstrated to inhibit all three yeast RNA polymerases both in vivo and in vitro, increases the RNA levels of HSP82 5- to 10-fold, those of SSA4 greater than 25-fold, and those of HSP26 greater than 50-fold under conditions in which transcription of non-heat-shock genes is blocked. By using an episomal HSP82-lacZ fusion gene, we present evidence that lyticase and thiolutin induce heat shock gene expression at the level of transcription, whereas phenanthroline acts at a subsequent step, likely through message stabilization. We conclude that, because of the exquisite sensitivity of the yeast heat shock response, procedures designed to measure the rate of gene transcription or mRNA turnover can themselves impact upon each process. PMID- 1938940 TI - Dosage of the smallest chromosome affects both the yeast-hyphal transition and the white-opaque transition of Candida albicans WO-1. AB - The WO-1 strain of Candida albicans is capable of alternating between two highly distinct yeast cell types termed white and opaque (E. H. A. Rikkerrink, B. B. Magee, and P. T. Magee, J. Bacteriol. 170:895-899, 1988; B. Slutsky, M. Staebell, J. Anderson, L. Risen, M. Pfaller, and D. R. Soll, J. Bacteriol. 169:189-197, 1987). We have isolated WO-1 mutants that show a marked deficiency at being able to switch from the white form to the opaque form under conditions normally favorable for this transition. Pulsed-field electrophoresis demonstrated that one of the initial two spontaneous nonswitching mutants lacked the smallest chromosome that is normally present in WO-1. The availability of a WO-1 derivative whose only functional ADE2 gene is located on this small chromosome made possible, through the induction of chromosome nondisjunction, the isolation of numerous new mutants missing this chromosome as well as mutants containing two copies of the chromosome. Mutants missing the smallest chromosome showed a greatly diminished ability to produce opaque sectors and to produce germ tubes in the presence of human serum. Mutants containing two copies of the small chromosome showed an increased ability to produce germ tubes. These results indicate that this small chromosome carries one or more genes involved in both the white-opaque switch and the yeast-hyphal switch. PMID- 1938941 TI - Bacillus subtilis CheN, a homolog of CheA, the central regulator of chemotaxis in Escherichia coli. AB - The Bacillus subtilis cheN gene was isolated, sequenced, and expressed. It encodes a large negatively charged protein with a molecular weight of approximately 74,000. The predicted protein sequence has 33 to 34% identity with the Escherichia coli and Salmonella typhimurium CheA and Myxococcus xanthus FrzE sequences. These proteins are found to autophosphorylate and are members of the same histidine kinase signal modulating family. CheN has several conserved regions (including the histidine that is phosphorylated in CheA) that coincide with other autophosphorylated signal transducers. A null mutant is defective in attractant-induced methanol formation and shows no behavioral response to chemoeffectors. These results imply that in B. subtilis the mechanism of chemotaxis involves phosphoryl transfer similar to that in E. coli. However, the CheN null mutant mostly tumbles, whereas CheA mutants swim smoothly, and only in B. subtilis does excitation lead to methyl transfer and methanol formation. Thus, the overall mechanism of chemotaxis is different in the two organisms. PMID- 1938942 TI - Copper-zinc superoxide dismutase of Haemophilus influenzae and H. parainfluenzae. AB - Copper-zinc superoxide dismutase ([Cu,Zn]-SOD) is widely found in eukaryotes but has only rarely been identified in bacteria. Here we describe sodC, encoding [Cu,Zn]-SOD in Haemophilus influenzae and H. parainfluenzae, frequent colonists and pathogens of the human respiratory tract. In capsulate H. influenzae, sodC was found in only one division of the bacterial population, and although the protein it encoded was clearly [Cu,Zn]-SOD from its deduced sequence, it lacked enzymatic activity. In H. parainfluenzae, in contrast, active enzyme was synthesized which appeared to be secreted beyond the cytoplasm when the gene was expressed in Escherichia coli minicells. The origin of gene transcription differed between the Haemophilus species, but protein synthesis from cloned genes in vitro was comparable. A C-T transition was found in the H. influenzae sequence compared with the H. parainfluenzae sequence, leading to a histidine, known to be crucial in eukaryotic [Cu,Zn]-SOD for copper ion coordination and so for enzymatic activity, to be changed to tyrosine. This is speculated to be the cause of inactivity of the H. influenzae enzyme. Secreted SODs have only been described in a few bacterial species, and this is the first identification of [Cu,Zn]-SOD in a common human upper respiratory tract colonist. The role of secreted bacterial SODs is unknown, and we speculate that in Haemophilus species the enzyme may confer survival advantage by accelerating dismutation of superoxide of environmental origin to hydrogen peroxide, disruptive to the normal mucociliary clearance process in the host. PMID- 1938943 TI - Transformation system for an asporogenous methylotrophic yeast, Candida boidinii: cloning of the orotidine-5'-phosphate decarboxylase gene (URA3), isolation of uracil auxotrophic mutants, and use of the mutants for integrative transformation. AB - An integrative transformation system was established for an asporogenous methylotrophic yeast, Candida boidinii. This system uses a uracil auxotrophic mutant of C. boidinii as the host strain in combination with its URA3 gene as the selectable marker. First, the C. boidinii URA3 gene coding for orotidine-5' phosphate decarboxylase (ODCase) was cloned by using complementation of the pyrF mutation of Escherichia coli. Next, the host ODCase-negative mutant strains (ura3 strains) were isolated by mutagenesis and selection for 5-fluro-orotic acid (5 FOA) resistance. Five ura3 host strains that exhibited both a low reversion rate and good methylotrophic growth were obtained. All of these strains could be transformed to Ura+ phenotype with a C. boidinii URA3-harboring plasmid linearized within the Candida DNA. The transformants had a stable Ura+ phenotype after nonselective growth for 10 generations. These results and extensive Southern analysis indicated that the linearized plasmid was integrated into the host chromosomal DNA by homologous recombination at the URA3 locus in C. boidinii. PMID- 1938944 TI - Characterization of the major promoter for the plasmid-encoded sucrose genes scrY, scrA, and scrB. AB - Sucrose genes from a Salmonella thompson plasmid were cloned in Escherichia coli K-12. A physical map and a genetic map of the genes were constructed, revealing strong homology with the scr regulon from the Salmonella typhimurium plasmid pUR400. Two promoters were examined after being subcloned into transcriptional fusion vectors. Primer extension analysis and site-directed mutagenesis were used to identify the precise location of the promoter of scrY, scrA, and scrB. Transcription from this promoter was regulated over a 1,000-fold range by the combined effects of ScrR-mediated repression and catabolite repression. A putative cyclic AMP receptor protein binding site centered 72.5 bp upstream of the start point of transcription of scrY appeared to be essential for full activity of the scrY promoter. Transcription from the putative scrK promoter was far less sensitive to repression by ScrR. In ScrR+ cells, readthrough transcription from the putative scrK promoter into scrY accounted for less than 10% of scrY expression. PMID- 1938945 TI - Multiple mechanisms contribute to osmotic inducibility of proU operon expression in Escherichia coli: demonstration of two osmoresponsive promoters and of a negative regulatory element within the first structural gene. AB - Transcription of the proU operon in Escherichia coli is induced several hundredfold upon growth of cells in media of elevated osmolarity. A low-copy number promoter-cloning plasmid vector, with lacZ as the reporter gene, was used for assaying the osmoresponsive promoter activity of each of various lengths of proU DNA, generated by cloning of discrete restriction fragments and by an exonuclease III-mediated deletion approach. The results indicate that expression of proU in E. coli is directed from two promoters, one (P2) characterized earlier by other workers with the start site of transcription 60 nucleotides upstream of the initiation codon of the first structural gene (proV), and the other (P1) situated 250 nucleotides upstream of proV. Furthermore, a region of DNA within proV was shown to be involved in negative regulation of proU transcription; phage Mu dII1681-generated lac fusions in the early region of proV also exhibited partial derepression of proU regulation, in comparison with fusions further downstream in the operon. Sequences around promoter P1, sequences around P2, and the promoter-downstream negative regulatory element, respectively, conferred approximately 5-, 8-, and 25-fold osmoresponsivity on proU expression. Within the region genetically defined to encode the negative regulatory element, there is a 116-nucleotide stretch that is absolutely conserved between the proU operons of E. coli and Salmonella typhimurium and has the capability of exhibiting alternative secondary structure. Insertion of this region of DNA into each of two different plasmid vectors was associated with a marked reduction in the mean topological linking number in plasmid molecules isolated from cultures grown in high-osmolarity medium. We propose that this region of DNA undergoes reversible transition to an underwound DNA conformation under high-osmolarity growth conditions and that this transition mediates its regulatory effect on proU expression. PMID- 1938946 TI - Mutations in rpoA affect expression of anaerobically regulated genes in Salmonella typhimurium. AB - oxrB8, a mutation that diminishes the anaerobic induction of pepT and other anaerobically regulated, oxrA (fnr)-dependent Salmonella typhimurium genes, is an allele of rpoA, the gene for the alpha subunit of RNA polymerase. Four additional rpoA mutations that affect anaerobic pepT expression have been isolated after localized mutagenesis of the rpoA region. All but one of these rpoA mutations appear to have relatively specific effects on genes that require the OxrA (FNR) protein, a positive transcriptional regulator of a family of anaerobically expressed genes. All of these mutations lead to amino acid substitutions in the C terminal region of the alpha subunit. These results taken with a number of previous observations suggest a role for the alpha subunit in the interaction between RNA polymerase and positive transcriptional regulatory proteins. They also suggest that the C-terminal region of alpha is important for these interactions. PMID- 1938947 TI - Expression of the psbDII gene in Synechococcus sp. strain PCC 7942 requires sequences downstream of the transcription start site. AB - The psbDI and psbDII genes in Synechococcus sp. strain PCC 7942 encode the D2 polypeptide, an essential component of the photosystem II reaction center. Previous studies have demonstrated that transcripts from psbDII, but not psbDI, increase in response to high light intensity. Soluble proteins from Synechococcus cells shifted to high light were found to have affinity for DNA sequences upstream from the psbDII coding region. DNA mobility-shift and copper phenanthroline footprinting assays of a 258-bp fragment revealed three distinct DNA-protein complexes that mapped to the untranslated leader region between +11 and +84. Deletion of the upstream flanking region to -42 had no effect on the expression of a psbDII-lacZ reporter gene or its induction by light, whereas a promoterless construct supported only minimal background levels of beta galactosidase. A 4-bp deletion within the first protected region of the footprint decreased the beta-galactosidase activity to approximately 2% of that of the undeleted control, but gene expression remained responsive to light. Deletion of the three protected regions completely abolished both gene expression and light induction. These results suggest that the psbDII gene requires elements within the untranslated leader region for efficient gene expression, one of which may be involved in regulation by light. PMID- 1938948 TI - Temporal sequence of the recovery of traits during phenotypic curing of a Cytophaga johnsonae motility mutant. AB - The lack of cell translocation and the resulting formation of nonspreading colonies of mutants of the gram-negative gliding bacterium Cytophaga johnsonae have been correlated with the loss of cell surface features of the organism. These cell surface traits include the ability to move polystyrene-latex beads over the cell surface and the ability to be infected by bacteriophages that infect the parent strain. In order to assess whether these traits reflect structures or functions that actually play a role in gliding, we studied a mutant (21A2I) selected for its inability to form spreading colonies; it is deficient in sulfonolipid, lacks bead movement ability, and is resistant to at least one bacteriophage. The provision of cysteate (a specific sulfonolipid precursor) restores lipid content and gliding to the mutant; hence, the lipids are necessary for motility. Growth with cysteate also restores bead movement and phage sensitivity. In order to determine the temporal relationship of these traits, we undertook a kinetic study of the appearance of them after addition of cysteate to the mutant. One predicts that appearance of a trait essential for cell translocation will either precede or accompany the appearance of this ability, while a nonessential trait need not do so. Sulfonolipid synthesis was the only trait that appeared before gliding; this is consistent with its established importance for motility. Bead movement and phage sensitivity first appeared only after gliding started, suggesting that the machinery involved in those processes is not necessary, at least for the initiation of gliding. PMID- 1938949 TI - Potential DNA slippage structures acquired during evolutionary divergence of Acinetobacter calcoaceticus chromosomal benABC and Pseudomonas putida TOL pWW0 plasmid xylXYZ, genes encoding benzoate dioxygenases. AB - The xylXYZ DNA region is carried on the TOL pWW0 plasmid in Pseudomonas putida and encodes a benzoate dioxygenase with broad substrate specificity. The DNA sequence of the region is presented and compared with benABC, the chromosomal region encoding the benzoate dioxygenase of Acinetobacter calcoaceticus. Corresponding genes from the two biological sources share common ancestry: comparison of aligned XylX-BenA, XylY-BenB, and XylZ-BenC amino acid sequences revealed respective identities of 58.3, 61.3, and 53%. The aligned genes have diverged to assume G+C contents that differ by 14.0 to 14.9%. Usage of the unusual arginine codons AGA and AGG appears to have been selected in the P. putida xylX gene as it diverged from the ancestor it shared with A. calcoaceticus benA. Homologous A. calcoaceticus and P. putida genes exhibit different patterns of DNA sequence repetition, and analysis of one such pattern suggests that mutations creating different DNA slippage structures made a significant contribution to the evolutionary divergence of xylX. PMID- 1938951 TI - Analysis of the upstream activating sequence and site of carbon and nitrogen source repression in the promoter of an early-induced sporulation gene of Bacillus subtilis. AB - The transcription from the spoVG promoter of Bacillus subtilis is induced at the start of the stationary phase of growth and is dependent on the expression of the spoOA, spoOB, and spoOH genes. It is repressed in cells grown in the presence of excess glucose and glutamine and is under the negative control of the abrB gene. The spoOA and spoOB gene products function to suppress the negative control exerted by abrB. Transcription initiation requires the form of RNA polymerase holoenzyme that contains the spoOH gene product, sigma H. Optimal transcription also requires an upstream A-T-rich region termed the upstream activating sequence (UAS). The mechanism of UAS function was examined through mutational analysis of the spoVG promoter region. Deletion of the UAS or positioning the UAS one half turn or one full turn of the DNA helix upstream of its location in wild-type spoVG resulted in a severe reduction in promoter activity. Deletion of most of the UAS abolished the abrB-dependent repression of spoVG transcription. Higher activity was observed when the UAS was inserted 10 bp (one turn of the helix) upstream than when the sequence was repositioned either 5 or 13 bp upstream. Sequences upstream of the UAS were found not to be involved with the position dependent function of the UAS. Positioning the UAS 42 or 116 bp upstream eliminated the stimulatory effect of the sequence on spoVG transcription. These data indicate that the UAS functions effectively when it is in close proximity to the -35 region. In vitro transcription analysis indicated that the deletion and insertion mutation affecting the UAS impair RNA polymerase-spoVG promoter interaction. Deletion of the UAS showed that the negative effect of exogenous glucose and glutamine is not dependent on the UAS but is exerted at a site within or near the -35 and -10 regions. PMID- 1938950 TI - Functional complementation between bacterial MDR-like export systems: colicin V, alpha-hemolysin, and Erwinia protease. AB - The antibacterial protein Colicin V (ColV) is secreted from gram-negative bacteria by a signal sequence-independent pathway. The proteins that mediate the export of ColV share sequence similarities with components from other signal sequence-independent export systems such as those for alpha-hemolysin (Hly) and Erwinia protease (Prt). We report here that the intact HlyBD export system can export active ColV from Escherichia coli strains lacking the ColV export proteins CvaA and CvaB. The individual Hly export genes complement mutations in their respective ColV homologs, but do so at a lower efficiency. When CvaA or CvaB is expressed along with the intact HlyBD exporter, the Cva export protein interferes with export of ColV through the HlyBD system. Gene fusions and point mutations in the ColV structural gene were used to define signals in ColV recognized by the Hly exporter. An export signal in ColV recognized by HlyBD is localized to the amino-terminal 57 amino acids of the protein. In addition, mutations in the ColV export signal differentially affect export through CvaAB and HlyBD, suggesting differences in signal specificity between the Cva and Hly systems. The three Erwinia protease export proteins can also export active ColV, and interference is seen when CvaA or CvaB is expressed along with the intact Prt exporter. Functional complementation is not reciprocal; alpha-hemolysin is not exported through either the ColV system or the Prt system. PMID- 1938953 TI - Replication and temperature-sensitive maintenance functions of lactose plasmid pSK11L from Lactococcus lactis subsp. cremoris. AB - The replication region of pSK11L, the lactose plasmid of Lactococcus lactis subsp. cremoris (L. cremoris) SK11, was isolated on a 14.8-kbp PvuII fragment by shotgun cloning into an Escherichia coli vector encoding erythromycin resistance and selection for erythromycin-resistant transformants of L. lactis subsp. lactis (L. lactis) LM0230. Deletion analysis and Tn5 mutagenesis of the resulting plasmid (pKMP1) further localized the replication region to a 2.3-kbp ScaI-SpeI fragment. DNA sequence analysis of this 2.3-kbp fragment revealed a 1,155-bp open reading frame encoding the putative replication protein, Rep. The replication origin was located upstream of rep and consisted of an 11-bp imperfect direct repeat and a 22-bp sequence tandemly repeated three and one-half times. The overall organization of the pSK11L replicon was remarkably similar to that of pCI305, suggesting that pSK11L does not replicate by the rolling-circle mechanism. Like pSK11L, pKMP1 was unstable in L. lactis LM0230. Deletion analysis allowed identification of several regions which appeared to contribute to the maintenance of pKMP1 in L. lactis LM0230. pKMP1 was significantly more stable in L. cremoris EB5 than in L. lactis LM0230 at all of the temperatures compared. This stability was lost by deletion of a 3.1-kbp PvuII-XbaI fragment which had no effect on stability in L. lactis LM0230. Other regions affecting stability in L. cremoris EB5 but not in L. lactis LM0230 were also identified. Stability assays conducted at various temperatures showed that pKMP1 maintenance was temperature sensitive in both L. lactis LM0230 and L. cremoris EB5, although the plasmid was more unstable in L. lactis LM0230. The region responsible for the temperature sensitivity phenotype in L. lactis LM0230 was tentatively localized to a 1.2-kbp ClaI-HindIII fragment which was distinct from the replication region of pSK11L. Our results suggest that the closely related L. lactis and L. cremoris subspecies behave differently regarding maintenance of plasmids. PMID- 1938952 TI - Nucleotide sequence and mutational analysis of the vnfENX region of Azotobacter vinelandii. AB - The nucleotide sequence (3,600 bp) of a second copy of nifENX-like genes in Azotobacter vinelandii has been determined. These genes are located immediately downstream from vnfA and have been designated vnfENX. The vnfENX genes appear to be organized as a single transcriptional unit that is preceded by a potential RpoN-dependent promoter. While the nifEN genes are thought to be evolutionarily related to nifDK, the vnfEN genes appear to be more closely related to nifEN than to either nifDK, vnfDK, or anfDK. Mutant strains (CA47 and CA48) carrying insertions in vnfE and vnfN, respectively, are able to grow diazotrophically in molybdenum (Mo)-deficient medium containing vanadium (V) (Vnf+) and in medium lacking both Mo and V (Anf+). However, a double mutant (strain DJ42.48) which contains a nifEN deletion and an insertion in vnfE is unable to grow diazotrophically in Mo-sufficient medium or in Mo-deficient medium with or without V. This suggests that NifE and NifN substitute for VnfE and VnfN when the vnfEN genes are mutationally inactivated. AnfA is not required for the expression of a vnfN-lacZ transcriptional fusion, even though this fusion is expressed under Mo- and V-deficient diazotrophic growth conditions. PMID- 1938954 TI - Genome conservation in isolates of Leptospira interrogans. AB - Reference strains for each of the 23 serogroups of Leptospira interrogans yielded different pulsed-field gel electrophoresis patterns of NotI digestion products. This was also the case for the 14 serovars belonging to serogroup Icterohaemorrhagiae (with one exception). The NotI restriction patterns of 45 clinical leptospiral isolates belonging to serovar icterohaemorrhagiae were analyzed and compared with those of type strains. No differences were observed between isolates from countries of different continents, namely, France, French Guiana, New Caledonia, and Tahiti. The pattern was indistinguishable from that of the reference strain of serovar icterohaemorrhagiae. PMID- 1938955 TI - Neisseria gonorrhoeae prepilin export studied in Escherichia coli. AB - The pilE gene of Neisseria gonorrhoeae MS11 and a series of pilE-phoA gene fusions were expressed in Escherichia coli. The PhoA hybrid proteins were shown to be located in the membrane fraction of the cells, and the prepilin product of the pilE gene was shown to be located exclusively in the cytoplasmic membrane. Analysis of the prepilin-PhoA hybrids showed that the first 20 residues of prepilin can function as an efficient export (signal) sequence. This segment of prepilin includes an unbroken sequence of 8 hydrophobic or neutral residues that form the N-terminal half of a 16-residue hydrophobic region of prepilin. Neither prepilin nor the prepilin-PhoA hybrids were processed by E. coli leader peptidase despite the presence of two consensus cleavage sites for this enzyme just after this hydrophobic region. Comparisons of the specific molecular activities of the four prepilin-PhoA hybrids and analysis of their susceptibility to proteolysis by trypsin and proteinase K in spheroplasts allow us to propose two models for the topology of prepilin in the E. coli cytoplasmic membrane. The bulk of the evidence supports the simplest of the two models, in which prepilin is anchored in the membrane solely by the N-terminal hydrophobic domain, with the extreme N terminus facing the cytoplasm and the longer C terminus facing the periplasm. PMID- 1938956 TI - Defects in gliding motility in mutants of Cytophaga johnsonae lacking a high molecular-weight cell surface polysaccharide. AB - We previously observed (W. Godchaux, L. Gorski, and E.R. Leadbetter, J. Bacteriol. 172:1250-1255, 1990) that two mutants (strains 21 and NS-1) of the gliding bacterium Cytophaga johnsonae that were totally deficient in motility dependent colony spreading, movement of rafts (groups) of cells as observed with a microscope, and movement of polystyrene-latex spheres that attached to the cell surface (observed in wet mounts) were also deficient in a high-molecular-weight cell surface polysaccharide (HMPS) and suggested a role for that substance in gliding motility. Antisera have been prepared against the purified HMPS, and these were used to select mutants specifically and highly deficient in the polysaccharide. All five such mutants had rates of colony spreading and raft movement that were much lower than those of the parent strain, but the rate of increase in colony diameter was higher than that found for strains NS-1 and 21 (which do not undergo raft movement at all). Unlike these latter two strains, the HMPS mutants retained the ability to move polystyrene-latex spheres over their surfaces. Hence, HMPS deficiency results in defective motility but not nonmotility, and the HMPS deficiency cannot fully explain the phenotype of mutants 21 and NS-1; in these strains, gliding must be affected by additional biochemical lesions. The HMPS may, nonetheless, be advantageous in that it supports greater gliding speeds. PMID- 1938957 TI - Function of MglA, a 22-kilodalton protein essential for gliding in Myxococcus xanthus. AB - Single mutations in the mglA gene in Myxococcus xanthus render cells incapable of gliding. The mglA strains are unique in that all other nonmotile strains of M. xanthus isolated are the result of at least two independent mutations in separate motility system genes. Translational fusions of trpE, or of lacZ, to mglA were constructed, and the resulting fusion polypeptides were used to generate antibodies. Antibodies specific to MglA protein were purified. Antibody-tagged MglA was found localized to the cytoplasm of M. xanthus cells both by fractionation of cell extracts and by electron microscopy of thin sections of whole cells. Four of the five mglA missense mutants tested failed to produce detectable levels of the MglA antigen in whole cell extracts. Nonmotile double mutants (A-S-), which have one mutation in a gene of system A and one mutation in a gene of system S, have the same phenotype as null mglA mutants but produce wild type levels of MglA protein. MglA protein is conserved in all strains of myxobacteria tested. The amino acid sequence of MglA protein includes three sequence motifs characteristic of GDP/GTP-binding proteins. On the basis of its genetic properties, intracellular location, and amino acid sequence, it is argued that MglA protein is a regulator in the sequence of functions leading to cell movement. PMID- 1938958 TI - Upstream gene of the mgl operon controls the level of MglA protein in Myxococcus xanthus. AB - The mgl operon contains two open reading frames (ORFs) which are transcribed together. A collection of nonmotile mutants helped to define the downstream ORF as the mglA gene. Single mutations at the mglA locus completely abolish motility. A series of deletion mutations was constructed to determine the role of the upstream ORF (now called mglB). A strain carrying a deletion in mglB and with an intact mglA produces small colonies. The cells are motile, but their rate of swarm spreading is reduced. Measurements of cell movement showed that mglB mutant cells advanced, on average, less than 0.1 cell length in 5 min. The mglB+ cells advanced an average of 1.3 cell lengths in the same time. Extracts of delta mglB cells contain 15 to 20% as much of the 22-kDa MglA protein as do mglB+ cells, as measured in Western immunoblots and enzyme-linked immunosorbent assays. However, the amount of mgl transcript is the same in the delta mglB mutants as in the mglB+ strain. Heterozygous partial diploids mglB/mglA with the wild-type alleles in trans have normal motility, demonstrating that the largest of the mglB deletions is not polar on mglA. Like other motility defects, a delta mglB mutation alters fruiting body development and sporulation. The mglB mutants delayed aggregation, produced small immature fruiting bodies, and sporulated at 45 to 50% wild-type levels. All aspects of the mglB mutant phenotype are explained by the reduced levels of mglA protein and the assumption that it limits the amount of gliding. PMID- 1938959 TI - A second gene in the Staphylococcus aureus cadA cadmium resistance determinant of plasmid pI258. AB - Two open reading frames on a 3.7-kb BglII-XbaI fragment which encodes the Staphylococcus aureus cadA cadmium (and zinc) resistance determinant of plasmid pI258 were identified (G. Nucifora, L. Chu, T. K. Misra, and S. Silver, Proc. Natl. Acad. Sci. USA 86:3544-3548, 1989). The [35S]methionine-labelled protein products of the 727-amino-acid CadA ATPase and of the 122-amino-acid CadC polypeptide in Escherichia coli were identified by using the T7 RNA polymerase promoter expression system. A truncated CadA polypeptide (402 amino acids) did not confer resistance in S. aureus but was expressed in E. coli under control of the T7 RNA polymerase-promoter. Removal of 678 nucleotides from the 5' end of the published sequence (which includes the cadA promoter) abolished resistance to cadmium, whereas a 146-nucleotide-shorter deletion was without effect. The cadC gene is needed in addition to cadA for full resistance to cadmium in S. aureus and Bacillus subtilis. cadC functions both in cis and in trans. PMID- 1938960 TI - Regulation of the cadA cadmium resistance determinant of Staphylococcus aureus plasmid pI258. AB - Regulation of the cadA cadmium and zinc resistance determinant of Staphylococcus aureus plasmid pI258 was demonstrated by using gene fusions and direct measurements of transcription. In growth experiments, cells harboring the intact cadA operon were induced with different cations and challenged by an inhibitory concentration of ZnCl2, a substrate of the CadA resistance system. Uninduced cells did not grow for 8 h after Zn2+ addition, whereas induced cells grew in the presence Zn2+. Cd2+ was a strong inducer, and Bi3+ and Pb2+ also induced well; Co2+ and Zn2+ were weak inducers. A translational beta-lactamase fusion to the cadA gene showed the same induction specificity as that seen with growth experiments with the intact cadA operon. A short beta-lactamase transcriptional fusion to the cadC gene also showed the same pattern of induction, establishing that the cadC gene was not involved in regulation. In Northern (RNA) blot hybridization experiments, a cadmium-inducible, 2.6-kb, operon-length transcript was detected. Primer extension experiments determined that Cd(2+)-inducible transcription of the cadA operon begins at nucleotides 676 and 677 of the published sequence (G. Nucifora, L. Chu, T. K. Misra, and S. Silver, Proc. Natl. Acad. Sci. USA 86: 3544-3548, 1989). PMID- 1938961 TI - Molecular and genetic analysis of a region of plasmid pCF10 containing positive control genes and structural genes encoding surface proteins involved in pheromone-inducible conjugation in Enterococcus faecalis. AB - Exposure of Enterococcus faecalis cells carrying the tetracycline resistance plasmid pCF10 to the heptapeptide pheromone cCF10 results in an increase in conjugal transfer frequency by as much as 10(6)-fold. Pheromone-induced donor cells also express at least two plasmid-encoded surface proteins, the 130-kDa Sec 10 protein, which is involved in surface exclusion, and the 150-kDa Asc10 protein, which has been associated with the formation of mating aggregates. Previous subcloning and transposon mutagenesis studies indicated that the adjacent EcoRI c (7.5 kb) and e (4.5 kb) fragments of pCF10 encode the structural genes for these proteins and that the EcoRI c fragment also encodes at least two regulatory genes involved in activation of the expression of the genes encoding Asc10 and Sec10. In this paper, the results of physical and genetic analysis of this region of pCF10, along with the complete DNA sequences of the EcoRI c and e fragments, are reported. The results of the genetic studies indicate the location of the structural genes for the surface proteins and reveal important features of their transcription. In addition, we provide evidence here and in the accompanying paper (S. B. Olmsted, S.-M. Kao, L. J. van Putte, J. C. Gallo, and G. M. Dunny, J. Bacteriol. 173:7665-7672, 1991) for a role of Asc10 in mating aggregate formation. The data also reveal a complex positive control system that acts at distances of at least 3 to 6 kb to activate expression of Asc10. DNA sequence analysis presented here reveals the positions of a number of specific genes, termed prg (pheromone-responsive genes) in this region of pCF10. The genes mapped include prgA (encoding Sec10) and prgB (encoding Asc10), as well as four putative regulatory genes, prgX, -R, -S, and -T. Although the predicted amino acid sequences of Sec10 and Asc10 have some structural features in common with a number of surface proteins of gram-positive cocci, and the Asc10 sequence is highly similar to that of a similar protein encoded by the pheromone-inducible plasmid pAD1 (D. Galli, F. Lottspeich, and R. Wirth, Mol. Microbiol. 4:895-904, 1990), the regulatory genes show relatively little resemblance to any previously sequenced genes from either procaryotes or eucaryotes. PMID- 1938962 TI - Role of the pheromone-inducible surface protein Asc10 in mating aggregate formation and conjugal transfer of the Enterococcus faecalis plasmid pCF10. AB - The high transfer frequency of pheromone-inducible conjugative plasmids of Enterococcus faecalis in liquid culture is due in part to the formation of mating aggregates. These aggregates result from the interaction of two surface components, aggregation substance (AS), which is plasmid encoded, and the chromosomally encoded binding substance (BS). In the accompanying paper (S.-M. Kao, S. B. Olmsted, A. S. Viksnins, J.C. Gallo, G. M. Dunny, J. Bacteriol, 173:7650-7664, 1991), the sequence of the prgB gene encoding the AS molecule (Asc10) produced by pheromone-induced cells carrying plasmid pCF10 is presented. Here we report the results of genetic and immunological experiments which define the role of Asc10 in aggregation and plasmid transfer. These data indicate expression of AS on the surface of an E. faecalis cell and its binding to BS expressed on a second cell are required for the formation of a mating pair and the efficient transfer of pCF10 in liquid matings. However, the orientation of the receptors was not critical for transfer; ie., AS expressed on recipient cells could facilitate plasmid transfer via binding to BS on the donor. Our results suggest that additional (as yet unidentified) products are involved in forming the channel that ultimately serves to transfer the DNA, with AS-BS binding serving primarily to generate the initial attachment between cells. The putative prgC gene product, identified by DNA sequencing (data presented in the accompanying paper), could be involved in transfer events occurring subsequent to aggregation. PMID- 1938963 TI - Sequence analysis of the clpG gene, which codes for surface antigen CS31A subunit: evidence of an evolutionary relationship between CS31A, K88, and F41 subunit genes. AB - The clpG gene coding for the CS31A subunit was localized on a 0.9-kb SphI fragment from the recombinant plasmid pAG315. This was established by testing the ability of subclones to hybridize with a 17-meric oligonucleotide probe obtained from N-terminal analysis of the CS31A subunit. The nucleotide sequence of the region coding for CS31A was determined. From primer extension analysis, two initiation translation start sites were detected. Two possible promoterlike sequences were identified; the ribosome binding site and the translation terminator are proposed. Inverted repeat sequences leading to the formation of possible hairpin structures of the transcripts were found on the 5' untranslated region of clpG. The deduced amino acid composition was in close agreement with the chemical amino acid composition and sequence match with the first 25 N terminal amino acids from the published N-terminal sequence of the purified CS31A subunit. The clpG gene codes for a mature protein of 257 amino acids with a molecular size of 26,777 Da. An obvious homology was observed when the amino acid sequence of CS31A was compared with those of K88 and F41. This homology includes five different conserved sequences of up to 19 identical amino acids, which is associated with conserved proline. An extensive change in the CS31A region homologous to that identified to contain the K88 receptor binding site might be responsible for the functional divergence between CS31A and K88. PMID- 1938965 TI - The Escherichia coli terB sequence affects maintenance of a plasmid with the M13 phage replication origin. AB - Replication initiated at the bacteriophage M13 origin can be affected by interaction of a properly oriented termination signal terB and the Tus protein. The effect can be alleviated by overproduction of the M13 replication gene protein II. PMID- 1938964 TI - Amount of peptidoglycan in cell walls of gram-negative bacteria. AB - The amount of diaminopimelic acid (Dap) in the cell wall of Escherichia coli was measured in two ways. A radiochemical method first described by us in 1985 (F. B. Wientjes, E. Pas, P. E. M. Taschner, and C. L. Woldringh, J. Bacteriol. 164:331 337, 1985) is based on the steady-state incorporation of [3H]Dap during several generations. Knowing the cell concentration and the specific activity of the [3H]Dap, one can calculate the number of Dap molecules per sacculus. The second method measures the Dap content chemically in sacculi isolated from a known number of cells. With both methods, a value of 3.5 x 10(6) Dap molecules per sacculus was obtained. Combined with electron microscopic measurements of the surface area of the cells, the data indicate an average surface area per disaccharide unit of ca. 2.5 nm2. This finding suggests that the peptidoglycan is basically a monolayered structure. PMID- 1938966 TI - Positive selection for uracil auxotrophs of the sulfur-dependent thermophilic archaebacterium Sulfolobus acidocaldarius by use of 5-fluoroorotic acid. AB - Uracil auxotrophs of Sulfolobus acidocaldarius were positively selected by using 5-fluoroorotic acid. The wild-type strain was unable to grow in medium containing 5-fluoroorotic acid, whereas the mutants grew normally. Positive selection could be done for the auxotrophs. Mutants deficient in orotidine-5'-monophosphate pyrophosphorylase activity were isolated. PMID- 1938967 TI - Molecular analysis of the TyrR protein-mediated activation of mtr gene expression in Escherichia coli K-12. AB - Expression of the mtr gene, which encodes a tryptophan-specific transport system in Escherichia coli K-12, is activated by the TyrR protein. Two TyrR protein binding sites (TYR R boxes) are positioned upstream of the -35 promoter region. Mutational and DNase protection studies indicate that TyrR protein binds preferentially to the TYR R box closest to the promoter, and this is essential for activation of gene expression. In the presence of tyrosine and ATP, a second TyrR molecule is able to cooperatively bind to the second box and cause a further increase in the level of activation. PMID- 1938969 TI - Isolation of mutants blocked in calicheamicin biosynthesis. AB - Blocked mutants of Micromonospora echinospora defective in the production of the potent antitumor agent calicheamicin are described. Analysis of intermediates produced by blocked mutants indicates a branched biosynthetic pathway. Mutants that produced some, but not all, calicheamicin forms are also described. PMID- 1938968 TI - Two beta-glycanase genes are clustered in Bacillus polymyxa: molecular cloning, expression, and sequence analysis of genes encoding a xylanase and an endo-beta (1,3)-(1,4)-glucanase. AB - Two genes, xynD and gluB, encoding a xylanase and an endo-beta-(1,3)-(1,4) glucanase (lichenase) from Bacillus polymyxa have been cloned and expressed in Escherichia coli and Bacillus subtilis. A sequenced DNA fragment of 4,466 bp contains both genes, which are separated by 155 bp. The xynD and gluB genes encode proteins of 67.8 kDa (XYND) and 27 kDa (GLUB). Two peptides with molecular masses of 62 and 53 kDa appear in cell extracts of E. coli and culture supernatants of B. subtilis clones containing the xynD gene. Both peptides show xylanase activity in zymogram analysis. The XYND enzyme also shows alpha-L arabinofuranosidase activity. The XYND peptide and the xylanase XYNZ from Clostridium thermocellum (O. Grepinet, M. C. Chebrou, and P. Beguin, J. Bacteriol. 170:4582-4588, 1988) show 64% homology in a stretch of about 280 amino acids. PMID- 1938970 TI - Escherichia coli alkaline phosphatase fails to acquire disulfide bonds when retained in the cytoplasm. AB - The cysteines of the Escherichia coli periplasmic enzyme alkaline phosphatase, which are involved in disulfide bonds in the native enzyme, were found to be fully reduced when the protein was retained in the cytoplasm. Under these circumstances the cysteines remained reduced for at least several minutes after the synthesis of the protein was completed. This contrasted with the normally exported protein, wherein disulfide bonds formed rapidly. Disulfide bond formation accompanied export and processing. The implications of these findings for the inactivity of the enzyme in the cytoplasm are discussed. PMID- 1938971 TI - A semiquantitative bioassay for relative virulence of Agrobacterium tumefaciens strains on Bryophyllum daigremontiana. AB - An assay to determine the relative virulence of wild-type and mutant strains of Agrobacterium tumefaciens on leaves of Bryophyllum daigremontiana has been developed. This assay is reproducible, is easy to learn, is not time consuming, and requires little space. The relative virulence of cellulose-minus mutants of A. tumefaciens was investigated with this assay. Some of these mutants were unaltered in virulence, while others showed a marked reduction in virulence. PMID- 1938972 TI - Selectable mutant phenotypes of the extremely thermophilic archaebacterium Sulfolobus acidocaldarius. AB - As a first step toward developing the genetic potential of extremely thermophilic archaebacteria, mutant strains of Sulfolobus acidocaldarius were selected by plating cells directly on solid medium containing one of several growth inhibitors. Three spontaneous resistance phenotypes were observed (5-fluorouracil resistance, novobiocin resistance, and L-ethionine resistance), each at a different average frequency. Characterization of representative strains showed each of the three mutant phenotypes to provide a potentially useful genetic marker. PMID- 1938973 TI - In vitro type II binding of chromosomal DNA to membrane in Bacillus subtilis. AB - DNA-membrane association critical for initiation of DNA replication in Bacillus subtilis can be classified into two types. Type I is salt resistant and dependent on the initiation gene, dnaB, and type II is salt sensitive and independent of the dnaB gene. We found and sequenced two adjacent areas of type II binding within 1% of oriC on the B. subtilis chromosome. PMID- 1938975 TI - An overview of chronic fatigue syndrome. AB - BACKGROUND: Psychological and immunologic factors both appear to contribute to chronic fatigue syndrome (CFS). By comparing CFS with other disorders in which fatigue is a prominent symptom, the association between fatigue, psychological vulnerability, depression, and immune function may be further defined. Recent data from psychological, neurologic, and immunologic studies that address these issues are reviewed. METHOD: Articles and abstracts covering CFS and related topics of fatigue, depression, and postinfectious syndromes were identified through MEDLINE and Index Medicus (1980-1990) and by bibliographic review of pertinent review articles. RESULTS: The 1988 definition of CFS by the Centers for Disease Control encompasses several conditions in which the major characteristic is severe fatigue associated with constitutional symptoms. Several studies have identified immune dysfunction in CFS patients, but the specificity of these findings remains unclear. Most studies have shown that CFS patients, compared with other patients with chronic medical illness, experience more disabling fatigue. Some investigators have found a higher incidence of concurrent and past psychiatric illness in CFS patients compared with other medical patients, thereby suggesting an underlying psychopathology in CFS. However, other studies have not found a higher than expected incidence of past depression in CFS patients and have further shown that many CFS patients have no identifiable psychopathology. CONCLUSION: CFS appears to be a heterogenous entity. Although there may be a high coincidence of major depression in CFS, a substantial proportion of patients lack any identifiable DSM-III-R psychiatric disorder yet still manifest the syndrome, thereby suggesting it has an autonomous entity. Despite the evolving nature of our current understanding of CFS, a rational diagnostic and therapeutic approach to CFS is possible. PMID- 1938974 TI - Induction of the alkA gene of Escherichia coli in gram-negative bacteria. AB - A broad-host-range plasmid containing a fusion of the alkA and lacZ genes of Escherichia coli was introduced into various aerobic and facultative gram negative bacteria--33 species belonging to 19 genera--to study the induction of expression of the alkA gene by alkylating agents. The bacteria included species of the families Enterobacteriaceae, Pseudomonadaceae, Rhizobiaceae, Vibrionaceae, Neisseriaceae, Rhodospirillaceae, and Azotobacteraceae. Results obtained show that all bacteria tested, except Aeromonas hydrophila, Agrobacterium tumefaciens, Hafnia alvei, Rhizobium meliloti, Salmonella enteritidis, Xanthomonas campestris, and those of the genus Rhodobacter, are able to induce the alkA gene of E. coli in the presence of N-methyl-N'-nitro-N-nitrosoguanidine. All these data indicate that the adaptive response to alkylating agents is present in bacterial species of several families and that the Ada box sequence must be widely conserved. PMID- 1938976 TI - Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder, and schizophrenia. AB - BACKGROUND: Although growing research indicates that the atypical antipsychotic agent clozapine is effective in patients with schizophrenia, little is known about the efficacy of clozapine in patients with schizoaffective disorder or psychotic mood disorders. The purpose of this study was to assess whether or not clozapine is effective in some patients with schizoaffective disorder or psychotic mood disorders. METHOD: By surveying treating clinicians and chart data, we assessed treatment response in 85 consecutive patients, including 39 with schizophrenia, 25 with schizoaffective disorder, and 14 with bipolar disorder with psychotic features, who received clozapine for at least 6 weeks at our center. RESULTS: All patients were either inadequately responsive to or unable to tolerate standard somatic therapies. Compared to patients with schizophrenia, patients with schizoaffective disorder and bipolar disorder with psychotic features displayed significantly higher response rates to clozapine. CONCLUSION: Clozapine may be a useful drug in the treatment of patients with schizoaffective disorder or psychotic mood disorders who are treatment resistant or intolerant of side effects. PMID- 1938977 TI - Estimated lifetime prevalence of trichotillomania in college students. AB - BACKGROUND: Trichotillomania, a disorder of hair pulling, has been considered a rare condition. Estimations of the prevalence of this disorder have been based largely on clinical experience, and there have been no estimates of its prevalence based on data collected from a large, nonclinical population. METHOD: 2579 freshman college students at two state universities and one liberal arts college were asked to provide written responses to questions designed to practically apply DSM-III-R criteria for trichotillomania and estimate the prevalence of trichotillomania in this population. RESULTS: 2534 students (97.9% of the study population) responded. We found a 0.6% lifetime prevalence of DSM III-R trichotillomania for both male and female respondents. Hair pulling resulting in visible hair loss, but failing to meet full DSM-III-R criteria, was identified in 1.5% of males and 3.4% of females. CONCLUSION: Trichotillomania may not be as rare as previously suspected and may affect males as often as females. PMID- 1938978 TI - Obsessive compulsive disorder, depression, and fluoxetine. AB - BACKGROUND: Fluoxetine, a selective serotonin reuptake blocker, is an antidepressant medication that has also been shown in open clinical trials and one controlled trial to be effective in the treatment of obsessive compulsive disorder (OCD). OCD is often complicated by depression, and depressive symptoms may interfere with response to both pharmacologic and behavioral treatments. METHOD: We describe pilot data from 10 outpatients who met DSM-III-R criteria for OCD in whom the possibility of a depressive reaction or lack of antidepressant response occurred during an open trial of fluoxetine. RESULTS: Rapid increase in fluoxetine dose to high doses was associated with depressive symptoms in 6 patients. In 8 patients, improvement in depression was associated with addition of a tricyclic antidepressant to fluoxetine treatment. In 5 patients, both OCD and depressive symptoms improved when the patient was switched to the partially selective serotonin reuptake blocker clomipramine. CONCLUSION: This paper serves to alert clinicians to the possibility of a depressive reaction, or lack of antidepressant response, to fluoxetine in OCD patients. This possibility can only be resolved scientifically by adequately controlled experimental trials. If depression occurs, combined fluoxetine and tricyclic treatment, or a switch to a partially selective serotonin reuptake inhibitor, may be helpful. Special considerations and side effects of combined fluoxetine-tricyclic treatment are described. PMID- 1938980 TI - Fluoxetine and dreaming. PMID- 1938979 TI - Prophylactic efficacy of maprotiline on unipolar depression relapse. AB - BACKGROUND: Although antidepressant medications have been in use for about 30 years, the question remains about their utility in the prophylaxis of recurrent depression. The purpose of this study was to evaluate the efficacy of maprotiline, a tetracyclic antidepressant, for depression prophylaxis. METHOD: We conducted a vast, prospective, multicenter, double-blind, placebo-controlled study of 1141 outpatients suffering from depression and treated with maprotiline or placebo for 1 year. The very large size of the study population allowed for the testing of two drug doses. The study design included a pre-inclusion treatment phase that assured that all study patients had recently suffered from a depressive episode and were in remission at the time they were randomized into two treatment groups (1 and 1/2 tablet of maprotiline 75 mg) and two control groups (1/2 and 1 tablet of placebo). RESULTS: The actuarial relapse rate at 1 year was 16% for maprotiline 75 mg, 1 tablet; 23.8% for maprotiline 75 mg, 1/2 tablet; 31.5% for 1 tablet placebo, and 37.5% for 1/2 tablet placebo. The difference between each group is statistically significant, except for the difference between the two placebo groups. The actuarial incidence of adverse drug reactions during the year was not statistically significant between the treatment and control groups. CONCLUSIONS: This study demonstrates maprotiline's prophylactic effectiveness for depressive relapses, the 75-mg dose being more effective than the 37.5-mg dose. The patients' tolerance of maprotiline therapy was satisfactory at both doses with prolonged prescription. PMID- 1938981 TI - Raised serum levels of desipramine with the antiarrhythmic propafenone. PMID- 1938982 TI - Defining recovery and remission. PMID- 1938984 TI - Depression: patient profile and treatment options. Confront issues with the experts. PMID- 1938983 TI - Surreptitious drug use by panic disorder patients. PMID- 1938985 TI - Comorbidity and medical complications of bulimia nervosa. AB - The syndrome of bulimia nervosa has been associated with a high rate of comorbidity with other psychiatric disorders. In particular, high rates of affective disorders, chemical dependency problems, anxiety disorders, and personality disorders have been described among these patients and, in some studies, among their relatives. The reasons for this elevated comorbidity remain unclear. It is frequently difficult to tell which condition develops first. Bulimia nervosa has also been associated with significant medical complications. Most patients with bulimia evidence metabolic and endocrine changes suggestive of a state of semistarvation. Fluid and electrolyte abnormalities are common, as are dental complications. Gastrointestinal complications are rare, but can be quite serious. A careful physical assessment is indicated for each bulimic patient. PMID- 1938986 TI - Nonpharmacologic treatments of bulimia nervosa. AB - The principal psychosocial approach to the treatment of bulimia nervosa has been cognitive-behavioral therapy, the effectiveness of which has been extensively documented in controlled trials, with full recovery (cessation of binge eating and purging) in some 50% to 60% of patients. More recently, interpersonal therapy, first introduced for the treatment of depression, has been shown in preliminary studies to be as effective as cognitive-behavioral therapy, particularly at follow-up. The evidence for effectiveness of psychosocial therapies in bulimia nervosa is first reviewed, and consideration is then given to what is known concerning the combination of psychosocial and psychopharmacologic treatment approaches and to the overall implications for the treatment of bulimia nervosa. PMID- 1938987 TI - Psychopharmacologic treatment of bulimia nervosa. AB - Much recent research on bulimia nervosa has focused on the development of pharmacologic treatments for this disorder. Of the various classes of compounds which have been tested to date, only the antidepressants have displayed consistent and reproducible antibulimic efficacy. Double-blind, placebo controlled trials have demonstrated that virtually all medications with antidepressant properties--tricyclic antidepressants, monoamine oxidase inhibitors, and atypical antidepressants, such as fluoxetine--significantly reduce the frequency of bingeing and purging in both depressed and nondepressed bulimics. However, the place of antidepressants in the overall treatment of bulimia nervosa remains unclear. Concerns about residual symptoms and long-term outcome, as well as the concomitant development of effective forms of psychotherapy, highlight the need for additional research to define an optimal therapeutic regimen for bulimia nervosa. PMID- 1938988 TI - Recent advances in bulimia nervosa. PMID- 1938989 TI - The course and outcome of bulimia nervosa. AB - Although knowledge of the long-term course and outcome of bulimia nervosa is critical to the effective management of the bulimic patient, research in this area is still in its infancy. Comparisons between existing outcome studies are complicated by differences in research design and methods, a lingering confusion over the definition of terms such as recovery and relapse, and the possibility of multiple forms of bulimia nervosa with varying outcomes. Nonetheless, these studies agree that bulimia nervosa is a chronic disorder, characterized by high rates of relapse and persistent subclinical symptomatology. Future investigations into the course and outcome of bulimia nervosa should focus on the derivation of a universally acceptable terminology and the identification of clinical and psychosocial variables predicting recovery. PMID- 1938990 TI - Family-genetic studies of eating disorders. AB - The possible contribution of genetic factors to the etiology of anorexia nervosa and bulimia nervosa is a question of mounting interest. Empirical studies are few in number, yet there is suggestive evidence of familial aggregation. The existing literature is reviewed and methodological problems are highlighted. It is suggested that predisposing elements are best accounted for by genetically transmitted dispositional traits, especially as are observed in the background of individuals with anorexia nervosa. PMID- 1938991 TI - Hematologic aspects of HIV disease: diagnostic and therapeutic considerations. PMID- 1938992 TI - Passive hyperimmune therapy in the treatment of AIDS and ARC. PMID- 1938993 TI - Impact of the HIV epidemic on therapeutic apheresis: nursing considerations. PMID- 1938994 TI - The Fenwal CS3000 inline pack is acceptable for donor blood sampling. AB - A blood sampling pack is available on closed system apheresis kits for the Fenwal CS3000 blood cell separator to facilitate same day donor testing while maintaining the closed system. Conceivably, the accuracy of complete blood counts (CBC) performed using pack samples might be compromised by clotting in the pack, by adherence of blood cells to the inner surface of the pack, or by dilution of the sample with priming fluid--should it inadvertently contaminate the pack. We studied paired blood samples collected simultaneously via the pack and a separate venipuncture in 17 donors. When collected properly, CBC values from pack and vein were nearly identical. Even when purposely contaminated with saline, pack values were lowered only slightly. Thus, the inline pack permits accurate sampling of donor blood for CBC while maintaining a closed system. PMID- 1938995 TI - Plateletpheresis with the new Fresenius AS 104 blood cell separator. AB - Among the many blood cell separators introduced into the international market in these last few years, the Fresenius AS 104 represents an advanced and safe thrombocytapheresis machine whose development took advantage of extensive worldwide experience with blood cell separation. Nonetheless the AS 104 has generated most interest in West Germany and most, if not all, the studies published on its platelet collection efficiency have been carried out in that country. It is normally reported that from 2.7 to 3.5 x 10(11) platelets can be collected in approximately 80 minutes. Since these results could not be duplicated routinely in our hemapheresis unit, we set up a study by modifying the standard procedure. It was possible to reduce the procedure time and to collect platelet concentrates containing more than 4 x 10(11) cells on a routine basis by using the following procedure: ACD-A/blood ratio 1:10; Interface position 6:2; blood flow rate always exceeding 65 mL/min; rpm 1750; cell collection from 4 to 7 mL/min; volume of blood processed 3.6 L followed by the rinsing of the system with 200 ml of saline; extraction of the content of the secondary separation chamber by the action of the plasma pump working at 20 mL/min for 2 min. With this procedure the platelet yield in 34 collections exceeded 3.1 x 10(11) and averaged 4.06 x 10(11). The procedure time was reduced to 56.5 minutes with a mean blood flow rate of 62.3 mL/min. The leukocyte and erythrocyte contamination of the products were in the range of 1 x 10(7) and 1 x 10(8) respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1938996 TI - Concentration of activated T lymphocytes in extracorporeal blood circulation for plasma separation. AB - To investigate whether the proportion of activated T lymphocytes changes in an extracorporeal blood flow, we compared paired samples collected at the inlet and outlet lines of an artificial circuit for plasma separation, using a dual immunofluorescence flow cytometric technique. In our series of materials from patients with rheumatoid arthritis or systemic lupus erythematosus, the percentages of HLA-DR-positive cells in both CD4+ (P less than 0.01, n = 6) and CD8+ (P less than 0.05, n = 10) subsets were significantly increased in the outlet lines compared with the inlet lines, suggesting that activated T lymphocytes pass through an extracorporeal blood circuit more easily than resting T lymphocytes. PMID- 1938997 TI - Status of therapeutic apheresis in Europe. AB - The development and future trend of therapeutic apheresis in Europe was analyzed. Demographic data on its distribution were collected with the help of the marketing departments of four commercial companies. The differences in application in European countries were examined and compared with North America and Japan. PMID- 1938998 TI - Experimental models of plasma perfusion. AB - A system allowing repeated plasma perfusion in the unrestrained conscious rat was developed in order to examine the effects of plasma filtration with on-line sorbent treatment of plasma in various models of disease. In experimental autoimmune glomerulonephritis, perfusion over a column coated with glomerular basement membrane (GBM) antigen lowered circulating levels of anti-GBM antibodies. In experimental endotoxaemia, perfusion over a column coated with polymixin B (PB) lowered circulating endotoxin levels and protected animals from haematological abnormalities and death. In experimental acute hepatic failure, perfusion over a combination of charcoal, resin, and PB columns improved survival in grades II and III hepatic coma. This experimental system has allowed preclinical evaluation of the effectiveness of different sorbents in the treatment of a range of disorders. PMID- 1938999 TI - Yeast gene which suppresses the defect in protein export of a secY mutant of E. coli. AB - To find factors participating in protein translocation in yeast, we screened a yeast genomic library for genes which, when introduced into Escherichia coli, suppressed secY24, a temperature sensitive mutation of an essential integral membrane protein (SecY) required for protein export. We isolated and characterized a gene (YSY6) which improved the translocation of the OmpA protein in mutant strain IQ85(secY24). It could also suppress another mutant [rplO215(Am)], in which the level of expression of the SecY protein is decreased at high-temperature. The YSY6 gene encodes a small amphiphilic peptide consisting of 65 amino acids, which can be expressed in E. coli cells. PMID- 1939000 TI - Does protein secretion activity vary during the cell cycle of Escherichia coli? AB - It is not known whether the activity of the Escherichia coli protein export system changes during the division cycle. To address and answer this question, we took two approaches. First, we pulse-labeled a random culture and size fractionated the labeled cells in the presence of inhibitors of secretion. Second, we pulse-labeled synchronously growing cells at different phases in the cell cycle. In the latter experiment, we used a new method of synchronization in which a random culture was simply filtered through glass fiber filters. In both cases, the proportions of unprocessed precursor molecules were measured by immunoprecipitation and gel electrophoresis for some representative periplasmic and outer membrane proteins. Within the sensitivity limits of these methods, we could not detect any significant variation in the precursor labeling for cells of different ages. Thus, E. coli cells appear to secrete proteins continuously throughout the division cycle. PMID- 1939001 TI - Both induction and activation of the branched-chain 2-oxo acid dehydrogenase complex in primary-cultured rat hepatocytes by clofibrate. AB - Clofibrate administration to rats caused both the activation and induction of the branched-chain 2-oxo acid dehydrogenase complex in the liver; the former phenomenon occurred within the first 6 h after clofibrate administration whereas the latter occurred after 12 h. Essentially the same results were obtained with primary cultures of rat hepatocytes in the presence of 0.5 mM clofibrate, though about three-fourths of the enzyme complex in control cells (without clofibrate addition) was inactivated during a culture for 44 h, with little reduction of the enzyme amount. This was also confirmed by immunotitration analysis with antibodies raised against the purified decarboxylase and transacylase components of the enzyme complex. On the other hand, the activity of dihydrolipoamide dehydrogenase (a constituent of the complex) was little affected by clofibrate administration. The half lives of the decarboxylase and transacylase components in the primary cultures were estimated to be in the range of 22-26 h, and were unchanged in the presence of clofibrate, when determined with the use of cycloheximide and by a pulse-chase experiment. On the contrary, the rates of synthesis of these two enzyme components had increased to about 1.9-fold after 32 h cultivation in the presence of clofibrate. Thus, the increase in the synthesis of both the components resulted in induction of the complex. PMID- 1939002 TI - Structure and organization of the mouse acrosin gene. AB - The genomic region carrying the mouse acrosin gene, including the 5'-flanking sequence, has been isolated and characterized. The acrosin gene consists of five exons separated by four introns. Organization of this gene is very similar to those of the genes for other typical serine proteases, except for the phase class of the first intron. Riboprobe mapping and primer extension analyses showed that the start site of transcription initiation in the acrosin gene is heterogeneous, including three major sites. Thus, the structure and organization of the mouse acrosin gene are different from those of the human gene [Keime, S., Adham, I.M., & Engel, W. (1990) Eur. J. Biochem. 190, 195-200] in two respects: the number of transcription initiation sites and the phase class of the third intron. The putative promoter regions of the mouse and human acrosin genes lack typical sequences of TATA, CAAT, and GC boxes, but contain a consensus sequence, GGGTGGG, known to be specific for the phosphoglycerate kinase-2 gene, and the protamine-1 and 2 genes that are uniquely expressed during spermatogenesis. PMID- 1939003 TI - Isolation and characterization of a lectin from the mushroom, Lactarius deliciosus. AB - A lectin (LDL) has been isolated from carpophores of the edible mushroom, Lactarius deliciosus, using a combination of affinity chromatography on stromas of group O erythrocytes embedded in polyacrylamide gel and hydroxylapatite, and gel filtration chromatography. Its molecular weight, as determined by gel filtration, is about 37,000 and its structure is dimeric, with two distinct types of subunits (about 19,000 and 18,000). It appeared homogeneous on HPLC gel filtration, but exhibited microheterogeneity on isoelectric focusing. Amino acid analysis revealed that it contains a large amount of glycine. Hapten inhibition assaying indicated that the Lactarius lectin is most specific for D-Gal beta 1--- 3D-GalNAc. The lectin was found in the mycelium and its possible role in the fungus is discussed. PMID- 1939004 TI - Role of an intrachain disulfide bond in the conformation and stability of ovalbumin. AB - Ovalbumin, which contains one intrachain disulfide bond and four cysteine sulfhydryls, was reduced with dithiothreitol under non-denaturing conditions, and its conformation and stability were compared with those of the disulfide-bonded form. The CD spectrum in the far-UV region revealed that the overall conformation of the reduced form is similar to that of the disulfide-bonded one. Likewise, the inaccessibility to trypsin and the non-reactivity of the four cysteine sulfhydryls, exhibited by the native disulfide-bonded ovalbumin, were still retained in the disulfide-reduced form. Thus, the reduced ovalbumin appeared to substantially take the native-like conformation. However, the near-UV CD spectrum slightly differed between the native and disulfide-reduced forms. Protein alkylation with a fluorescent dye and subsequent sequence analysis showed that the two sulfhydryls (Cys73 and Cys120) originating from the disulfide bond are highly reactive in the reduced form. Furthermore, upon proteolysis with subtilisin, the N-terminal side of Cys73 was cleaved in the reduced form, but not in the disulfide-bonded one. Upon heat denaturation, the transition temperature of the reduced form was lower, by 6.8 degrees C, than that of the disulfide bonded one. Thus, we concluded that ovalbumin has a native-like conformation in its disulfide-reduced form, but that the local conformation of the reduced form fluctuates more than that of the disulfide-bonded one. Such local destabilization may be related to the decreased stability against heat denaturation. PMID- 1939005 TI - Molecular cloning and nucleotide sequence of 3-isopropylmalate dehydrogenase gene (leuB) from an extreme thermophile, Thermus aquaticus YT-1. AB - A gene (leuB) coding for 3-isopropylmalate dehydrogenase [EC 1.1.1.85] from an extreme thermophile, Thermus aquaticus YT-1 was cloned in Escherichia coli and the nucleotide sequence was determined. It contains an open reading frame of 1,035 bp encoding 344 amino acid residues. The homology with that from T. thermophilus HB8 is 87.0% in nucleotide and 91.3% in amino acid sequences. No overlapped gene was found in the present leuB gene, in contrast to the previous prediction that Thermus leuD gene is overlapped with leuB [Croft et al. (1987) Mol. Gen. Genet. 210, 490-497]. Substitutions in the primary structure which are unique for the thermophile sequences are discussed in relation to the unusual stability of the thermophile dehydrogenase based on amino acid sequence comparison of 9 microorganisms including thermophiles and mesophiles. PMID- 1939007 TI - Genomic organization of a Drosophila phospholipase C, norpA, and molecular lesions in two temperature-sensitive mutants. AB - The Drosophila mutant no receptor potential A (norpA) is the phototransduction defective mutant which lacks phosphatidylinositol-specific phospholipase C (PI PLC) activity. Recently, norpA cDNA was isolated and its homology to a bovine PI PLC was demonstrated [Bloomquist, B.T. et al. (1988) Cell 54, 723-733]. On the basis of its cDNA, we determined the genomic organization of the norpA gene and revealed that the norpA gene consists of 13 coding exons spreading over a 15 kb genomic area. Furthermore, we identified the mutational sites of two temperature sensitive (ts) mutants. The analysis of norpAH52 revealed that the single amino acid change from Ser-551 to Tyr causes the PI-PLC activity to become temperature sensitive. The other allele, norpAKO50, has two substitutions from Ser-406 to Phe and from Gly-451 to Ser. These three mutations are located in regions highly conserved in other mammalian PI-PLC molecules. This suggests that these regions are important for PI-PLC catalytic activity. PMID- 1939006 TI - In vitro movement of actin filaments on gizzard smooth muscle myosin: requirement of phosphorylation of myosin light chain and effects of tropomyosin and caldesmon. AB - ATP-dependent movement of actin filaments on smooth muscle myosin was investigated by using the in vitro motility assay method in which myosin was fixed on the surface of a coverslip in a phosphorylated or an unphosphorylated state. Actin filaments slid on gizzard myosin phosphorylated with myosin light chain kinase (MLCK) at a rate of 0.35 micron/s, but did not slide at all on unphosphorylated myosin. The movement of actin filaments on phosphorylated myosin was stopped by perfusion of phosphatase. Subsequent perfusion with a solution containing MLCK, calmodulin, and Ca2+ enabled actin filaments to move again. The sliding velocities on monophosphorylated and diphosphorylated myosin by MLCK were not different. Actin filaments did not move on myosin phosphorylated with protein kinase C (PKC). The sliding velocity on myosin phosphorylated with both MLCK and PKC was identical to that on myosin phosphorylated only with MLCK. Gizzard tropomyosin enhanced the sliding velocity to 0.76 micron/s. Gizzard caldesmon decreased the sliding velocity with increase in its concentration. At a 5-fold molar ratio of caldesmon to actin, the movement stopped completely. This inhibitory effect of caldesmon was relieved upon addition of excess calmodulin and Ca2+. PMID- 1939008 TI - Identification and distribution of tropomyosin isoforms in chicken digestive canal. AB - Two-dimensional gel electrophoresis of eight digestive organ extracts from 60-day old chicks was performed. Judging from the similarity of their protein maps, the organs were classified into the following four types: 1) esophagus type, 2) proventriculus type, 3) gizzard type, and 4) intestine type. In four representative organs of these types, the distribution of tropomyosin isoforms was examined, and four high- and five low-Mr-type isoforms in addition to alpha and beta isoforms were detected in the embryonic organs. In the adult organs, however, there were three high- and four low-Mr-type isoforms, which were restricted to the mucous membrane, in addition to alpha and beta isoforms. Immunoblot analysis indicated that the high- and low-Mr-type isoforms in the embryo corresponded with those in the adult mucous membrane, but differences in the number and amount of the isoforms were found between the embryo and the adult mucous membrane. PMID- 1939009 TI - Metabolism of sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate in hamsters. AB - Metabolism of sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate, the sulfonate derivative of chenodeoxycholic acid, was studied in hamsters. In bile fistula hamsters, the sulfonate analogue was efficiently absorbed from the ileum and secreted rapidly into the bile without any modification such as conjugation. However, absorption from the jejunum was smaller than that observed for the ileum. After oral administration, the sulfonate analogue of chenodeoxycholic acid was recovered quantitatively in the feces as the unchanged form in contrast to simultaneously administered chenodeoxycholic acid, which was entirely converted to lithocholic acid during its passage through the intestinal tract. These results demonstrate that the sulfonate analogue is absorbed mainly from the ileum by active transport, enters the enterohepatic circulation like the endogenous conjugated bile acids, and completely resists bacterial degradation. PMID- 1939011 TI - Characterization and changes of glycosphingolipids in the aorta of the Watanabe hereditable hyperlipidemic rabbit. AB - Characterization and elucidation of the changes of glycosphingolipids in the aorta along with the progression of atherosclerosis were performed in the Watanabe hereditable hyperlipidemic (WHHL) rabbit, an animal model for human familial hypercholesterolemia, as compared with in the normal rabbit. Neutral glycosphingolipids in aortae of both normal and WHHL rabbits were composed of glucosylceramide, galactosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, and galactosylneolactotetraosylceramide. The total amount of neutral glycosphingolipids in the aorta of the WHHL rabbit (557 nmol/g tissue) was increased about 5-fold compared to the normal level (107 nmol/g tissue). Prominent increases were observed in glucosylceramide (13-fold the normal level) and lactosylceramide (12-fold the normal level). The amount of total gangliosides in the aorta of the WHHL rabbit (207 micrograms NeuAc/g tissue) was markedly increased, being about 12-fold the normal level (17 micrograms NeuAc/g tissue). GM3 ganglioside was increased about 11-fold compared to normal. GD3 ganglioside, which was almost undetectable in normal aorta, also showed a marked increase in that of the WHHL rabbit (51.7 micrograms NeuAc/g tissue). Sulfatide, which was absent in the aorta of the normal rabbit, was markedly accumulated in that of the WHHL rabbit (280 nmol/g tissue). The fatty acid composition of neutral glycosphingolipids of WHHL rabbit was found to include a higher amount of C23:0, which is the major fatty acid of glycolipids in serum lipoproteins. Gangliosides in the aorta of the WHHL rabbit contained more C16:0 than in the normal rabbit. Sphingosine of sulfatide in the aorta of the WHHL rabbit was composed of sphingenine (86%), sphinganine (9%), 4-D-hydroxysphinganine (4%), and 4-D hydroxyeicosasphinganine (less than 1%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939010 TI - Expression of a synthetic gene for human cap binding protein (human IF-4E) in Escherichia coli and fluorescence studies on interaction with mRNA cap structure analogues. AB - An artificial gene coding for the human cap binding protein (hCBP: human IF-4E) was chemically synthesized and expressed in Escherichia coli under the control of a trp promoter. The DNA duplex of 662 bp was designed and constructed from 44 oligodeoxynucleotide fragments of typically 30 nucleotides in length. Although the hCBP gene was not directly expressed in E. coli HB101, we succeeded in its high-level expression as a fusion protein connected with a portion of human growth hormone through a tetradecapeptide (Asp-Asp-Pro-Pro-Thr-Val-Glu-Leu-Gln Gly-Leu-Val-Pro-Arg) that contains the recognition sequence for a site-specific protease alpha-thrombin. Upon induction with 3-indoleacrylic acid, the fusion protein accumulated with a yield of about 20% of the total proteins of the host cell. Upon the treatment of the fusion protein with alpha-thrombin, which recognizes the sequence "Val-Pro-Arg," specific proteolysis at the fused junction occurred efficiently. In this system, nonspecific digestion by alpha-thrombin was not marked. About 15 mg of recombinant hCBP was obtained from a 1-liter culture. Association constants between the recombinant hCBP and mRNA cap structure analogues were determined by fluorescence spectroscopy. The values obtained for the m7GpppA, m7GTP, and m7GMP were almost the same as those reported for the IF 4E isolated from human erythrocyte cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939012 TI - Cysteine residues in the active site of Corynebacterium sarcosine oxidase. AB - Sarcosine oxidase from Corynebacterium sp. U-96 is inhibited by iodoacetamide (IAM) and the inhibition is prevented by the substrate analog, sodium acetate. To elucidate the mechanism of inhibition of the enzyme by IAM, we determined the amino acid sequences around the IAM-reactive cysteine residues, and the effects of the modification on the enzyme activity and the oxidation-reduction of the FAD moieties of the enzyme. The enzyme was specifically labeled with [14C]IAM, and the labeled subunit B was digested with trypsin and chymotrypsin. The HPLC profiles of the proteolytic digests showed mainly two radioactive peaks. The 14C labeled peptides were purified, and their N-terminal sequences were determined to be Cys-Gly-Thr-Pro-Gly-Ala-Gly-Tyr (TC-1) and Ala-Gly-Ile-Ala-Cys-Xaa-Asp-Xaa-Val Ala(-)- (TC-2). Peptide TC-2 contains a covalent FAD-binding sequence [Asx-His Val-Ala; Shiga et al. (1983) Biochem. Int., 6, 737]. [14C]IAM-incorporation into the TC-1 sequence was strongly inhibited by sodium acetate. The N-terminal amino acid sequence of the CNBr fragment containing the TC-1 sequence (65 residues) was determined. According to the secondary structure predictions, Gly-Thr-Pro-Gly-Ala Gly of the TC-1 sequence is located between the beta sheet and alpha helix of the sequence, indicating the presence of an AMP-binding site in the TC-1 region. The activity of the enzyme treated with IAM in the presence and absence of sodium acetate was not inhibited by sodium sulfite, which is known to react specifically with covalent FAD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939013 TI - Tissue specific expression of the plasma glutathione peroxidase gene in rat kidney. AB - Rat plasma glutathione peroxidase (GSH-Px) was purified 1,400-fold from rat serum by a combination of phenyl Sepharose, DEAE Sephacel, blue Sepharose and Sephacryl S-200 column chromatographies. The purified GSH-Px migrated as a single band corresponding to a molecular weight of 22,500 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme was used for the immunization of chickens to obtain a specific antibody and for determination of its amino acid sequence. Two overlapping cDNA clones for rat plasma GSH-Px were isolated from a placental cDNA library. The composite nucleotide sequence is 1,529 base-pairs long and encodes 226 amino acids. The deduced amino acid sequence completely coincided with the sequences of five individual peptide fragments derived from the purified plasma GSH-Px on digestion with lysyl endopeptidase. In order to identify the tissue(s) generating this plasma GSH-Px, immunoblot analysis was performed on homogenates prepared from 13 tissues. A single immunoreactive band of 22.5 kDa, corresponding to plasma GSH-Px, was detected for the kidney homogenate. A much fainter band was observed for the lung preparation, but liver, spleen, bone marrow, and other tissues examined were negative. Northern blot analysis further revealed that the expression level of the plasma GSH-Px gene was high in kidney and low in lung. No transcript was detected in liver or spleen. These results indicate that plasma GSH-Px is predominantly synthesized and secreted by renal cells. PMID- 1939014 TI - Reconstitution of new inhibitors through mutual exchange of Ile(64)-Met(84) peptides of soybean trypsin inhibitors, Tia and Tib. AB - Singly modified soybean trypsin inhibitors (STIs), Tia* [Tia cleaved at Arg(63) Ile(64)] and Tib* [Tib cleaved at Arg(63)-Ile(64)], were prepared by limited proteolysis with trypsin at pH 3.0. These singly modified inhibitors were further modified to yield doubly modified inhibitors, Tia** and Tib**, by limited proteolysis with subtilisin BPN', which cleaved the Met(84)-Leu(85) bonds of Tia* and Tib*, respectively. The doubly modified inhibitors could be separated into two parts: protein moiety A and peptide moiety a (IRFIAEGHPLSLKFDS-FAVIM) for Tia**, and protein moiety B and peptide moiety b (IRFIAEGNPLRLKFDS-FAVIM) for Tib**. These protein and peptide moieties showed no trypsin inhibitory activities alone. However, the inhibitors can be reconstituted through the mutual exchange of the protein and peptide moieties isolated from STIs. The reconstituted inhibitor which has tyrosine at position 62 and histidine at position 71 shows the highest inhibitory activity. Its Ki value for bovine trypsin is around 10( 10) M, which is almost the same as that of Tia for bovine trypsin. The inhibitor possessing either tyrosine at position 62 or histidine at position 71 exhibits a Ki value of around 10(-9) M, which is between those of Tia and Tib. The inhibitor having phenylalanine and asparagine at positions 62 and 71, respectively, shows the weakest inhibitory activity of around 10(-8) M similar to that of Tib for bovine trypsin. PMID- 1939015 TI - Secretory expression of the human serum albumin gene in the yeast, Saccharomyces cerevisiae. AB - We have fused a cDNA gene encoding mature human serum albumin (HSA) to several secretory leader-encoding sequences. The hybrid genes were cloned into an episomal vector under the control of several yeast promoters and then introduced into yeast cells. The GAL1 promoter in combination with either the native HSA pre sequence or a modified HSA pre-sequence gave the highest production of immunoreactive HSA, 90 mg/liter being reached in a shake flask culture. The invertase pre-sequence, the mating factor alpha 1 prepro-sequence, and the modified HSA pre-sequence directed accurate processing. In contrast, the chicken lysozyme pre-sequence and the native HSA pre-sequence directed incorrect processing. Episomal vectors were unstable within the host cells under non selective culture conditions. To improve the plasmid stability, the hybrid genes were incorporated into an integrative vector. Transformants carrying multicopies of the plasmid integrated at the LEU2 locus stably secreted HSA. The highest yield of 65 mg/liter in a shake flask culture was obtained with the combination of the yeast glyceraldehyde-3-phosphate dehydrogenase promoter and the modified HSA pre-sequence. By constructing transformed strains containing multicopies of plasmids integrated at both the chromosome LEU2 and HIS4 loci, we have obtained a stable strain that continuously secretes as much as 85 mg HSA per liter of culture medium. PMID- 1939016 TI - The nucleotide sequence for a proline-activating domain of gramicidin S synthetase 2 gene from Bacillus brevis. AB - A fragment encoding proline-activating domain (grs 2-pro) of gramicidin S synthetase 2 (GS 2) was found in an 8.1-kilobase pairs (kb) DNA fragment of Bacillus brevis Nagano, which contained the full length of GS 1 gene (grs 1). The clones designated GS719 and GS708, which expressed gramicidin S synthetase 1, were elucidated to express immunoreactive proteins to GS 2 antibodies with approximate molecular weights of 115,000, 105,000 (GS719), and 110,000 (GS708). The partial purification of the gene products of these clones was carried out using DEAE-Sepharose CL-6B column chromatography. The immunoreactive proteins to GS 2 antibodies were separated from gramicidin S synthetase 1 protein and had specific proline-dependent ATP-32PPi exchange activity. The nucleotide sequence for the proline-activating domain in the 8.1-kb insert was determined. This fragment was 2,879 base pairs long, and encoded 959 amino acids. The calculated molecular weight of 111,671 was consistent with the apparent molecular weight of 115,000 found in SDS-PAGE of the immunoreactive products to GS 2 antibodies. The open reading frame for this protein followed grs 1 gene, though two were separated by a 73-base pair noncoding sequence, and remained open to the end.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939018 TI - Glycosphingolipids of human large intestine: detailed structural characterization with special reference to blood group compounds and bacterial receptor structures. AB - Non-acid glycosphingolipid expression was studied in the large intestines from four individuals with the A1Le(a-b+), BLe(a-b+), and OLe(a-b+) blood group phenotypes. In the A1Le(a-b+) case, specimens were taken from the ascending and sigmoid parts of the large intestine in order to compare the expression of glycolipids in the proximal and distal regions of the intestine. In one blood group OLe(a-b+) individual, epithelial cells were isolated from the residual stroma to compare the glycolipid compositions in these two tissue compartments. GlcCer, GalCer, LacCer, Gb3Cer, and Gb4Cer were the major compounds in all three individuals, as shown by mass spectrometry, proton NMR spectroscopy, and degradation studies. The Lea-5 glycolipid was the major complex blood group glycolipid in all individuals, except in the proximal ascending part of the large intestine of the A1Le(a-b+) case, in which the Leb-6 glycolipid was predominant. There were trace amounts of blood group ABH glycolipids, in agreement with the ABO blood group phenotypes of the donors, Lewis antigens with more than six sugar residues in the carbohydrate chain, and blood group X and Y glycolipid antigens. The epithelial cells were dominated by monoglycosylceramides and the Lea-5 glycolipid, while only trace amounts of di-, tri-, and tetraglycosylceramide structures were present. No reactivity was seen in the epithelial cell fraction with Gal alpha 1-4Gal specific Escherichia coli, anti-Pk, or anti-P antibodies, indicating the absence of the glycolipid-borne Gal alpha 1-4Gal sequence in human large intestinal epithelial cells. PMID- 1939019 TI - Application of 2-aminopyridine fluorescence labeling to glycosaminoglycans. AB - A pyridylamination method was applied to glycosaminoglycans and the characteristics of the resulting pyridylamino glycosaminoglycans were examined. First, glycosaminoglycan chains, which uniformly possess a xylose residue at their reducing termini, were liberated from proteoglycan by successive digestion with protease and endo-beta-xylosidase. Then the glycosaminoglycan chains were coupled with 2-aminopyridine by reductive amination with sodium cyanoborohydride for 15 h according to the method of Hase, S. et al. [J. Biochem. 95, 197-203 (1984)]. The pyridylamination reaction caused neither depolymerization, de-N acetylation, nor de-N- or de-O-sulfation. The pyridylamino glycosaminoglycan chains had an intact linkage region (GlcA-Gal-Gal-Xyl) between the carbohydrate chain and the peptide core of the proteoglycan. These pyridylamino glycosaminoglycans should be useful as substrates for endo-type glycosidases that act on glycosaminoglycan chains and as markers for studies of glycosaminoglycan metabolism. PMID- 1939020 TI - Purification and characterization of a sea squirt beta-galactosidase. AB - A beta-galactosidase was extracted from the internal organs of a sea squirt, Styela plicata, and purified 959-fold, with an 18% yield, by successive gel chromatography, anion-exchange chromatography, chromatofocusing, and affinity chromatography on a Con A-Sepharose column. The purified enzyme was fairly homogeneous, as judged on disc PAGE, SDS-PAGE, and gel chromatography on a Sephadex G-200 column. The molecular weight of the enzyme was estimated to be 77,000 and 75,000 by gel chromatography and SDS-PAGE, respectively, and its isoelectric point was determined to be 4.9 by the isoelectric focusing method. The enzyme was substantially stable in the pH range of 3.5 to 7.5, the optimum pH being 4.0. The enzyme was significantly inhibited by 9 mM HgCl2 and 9 mM DFP, while the inhibition by 0.9% PCMB was only 60% at 0 degrees C for 30 min. The purified beta-galactosidase apparently liberated galactose from a sea squirt antigen (H-antigen), two allergenically active glycopeptides (Gp-1 and Gp-2) derived from another sea squirt antigen (Gi-rep), asialo-ovomucoid glycopeptide, asialo-fetuin glycopeptide, GA1, CDH, and an ABEE-derivative (Gal beta 1--- 3ThrNAc-ABEE) of Gal beta 1----3GalNAc-ol isolated from bovine submaxillary gland mucin. PMID- 1939017 TI - Molecular parameters of gangliosides in monolayers: comparative evaluation of suitable purification procedures. AB - The molecular area, collapse pressure, and surface potential of gangliosides obtained by different methods were systematically compared in monolayers at the air-water interface. Different values of these parameters are obtained depending on the purification procedure employed for the isolation of pure gangliosides. This is due to impurities (such as peptidaceous material) that remain in different amounts in the various preparations and that modify the ganglioside surface behavior. Routine purity checking by HPTLC analysis of gangliosides usually fails to reveal these impurities. On the other hand, even if the monolayer technique cannot identify the nature or amount of contaminants, it is extremely sensitive to reveal alterations of the surface molecular parameters caused by relatively small amounts of other components coextracted with the ganglioside or adventitiously introduced with the solvents or subphases employed. This is a serious problem for the obtention of correct and reproducible values of such important parameters as the molecular area of gangliosides, their electrostatic potential in oriented interfaces, and their interactions with other lipids and proteins. A procedure leading to consistent molecular parameters that remain reproducible after several repurification cycles is to perform an alkaline treatment on previously purified gangliosides species with NaOH, this is followed by dialysis against bidistilled water, rechromatography on DEAE-Sephadex A25, silicic acid or Iatrobeads, and Sephadex LH-20 columns; repurified gangliosides are stored in chloroform-methanol-0.01 M NaOH (60:30:4.5). PMID- 1939021 TI - Characterization of the hydrophobic region of heat shock protein 90. AB - The modes of binding of heat shock protein 90 with phenyl-Sepharose, myristoylated AE-cellulose, and monomyristoylated lysozyme were studied to characterize a hydrophobic region(s) on the surface of the heat shock protein 90 molecule and the following results were obtained. (1) The binding of heat shock protein 90 with phenyl-Sepharose was inhibited by the addition of 30% ethylene glycol. This indicates that the binding involves a hydrophobic interaction. (2) The binding was strengthened by the addition of 10 mM Mg2+, Ca2+, Sr2+, and Ba2+ ions, but not by K+ or Na+ ions. (3) The binding of hsp 90 with phenyl-Sepharose decreased initially and then increased as the temperature was increased from 0 to 50 degrees C, with a minimum at around 35 degrees C. (4) Lowering the pH stimulated the binding of hsp 90 with phenyl-Sepharose. (5) Heat shock protein 90 bound to myristoylated AE-cellulose, which has aliphatic hydrophobic residues, but not to acetylated AE-cellulose. (6) Heat shock protein 90 bound to monomyristoylated lysozyme, but not to control unmodified lysozyme. Based on these results, the possible function of the hydrophobic region(s) of heat shock protein 90 in the interaction with hydrophobic proteins is discussed. PMID- 1939022 TI - Amino acid sequence of nuclease S1 from Aspergillus oryzae. AB - The amino acid sequence of nuclease S1, a nuclease which cleaves both single stranded DNA and RNA, from Aspergillus oryzae was determined. Reduced and S carboxymethylated or S-aminoethylated nuclease S1 was digested with Achromobacter protease I, Staphylococcus aureus V8 protease, or endoproteinase Asp-N. Peptides thus obtained were purified by reverse-phase high-performance liquid chromatography and sequenced, and the complete primary structure was established. Nuclease S1 consists of a single peptide chain of 267 amino acid residues bearing N-glycosylated Asns 92 and 228. Five half-cystine residues are present at positions 25, 72, 80, 85, and 216, and the latter four residues are implicated in the formation of disulfide bonds by analogy with those in nuclease P1. Two short stretches of sequences involving His 60 and His 125 are shown to be identical with those involving active site His 119 in bovine ribonuclease A and active-site His 134 in porcine deoxyribonuclease I, respectively. PMID- 1939023 TI - Purification and characterization of neutral alpha-mannosidase that is activated by Co2+ from Japanese quail oviduct. AB - An alpha-mannosidase was purified from the magnum section of Japanese quail oviduct by ammonium sulfate precipitation, DEAE-Sephacel chromatography, Sephacryl S-300 chromatography, mannan-Sepharose 4B chromatography, and hydroxyapatite chromatography. The purified alpha-mannosidase (referred to as neutral alpha-mannosidase) showed a single band on polyacrylamide gel with or without sodium dodecyl sulfate. Its molecular weight was found to be 330,000 by gel chromatography. Neutral alpha-mannosidase hydrolyzed p-nitrophenyl alpha-D mannopyranoside and the pyridylamino derivative of Man alpha 1-6(Man alpha 1 3)Man alpha 1-6(Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc (Km value was 3 mM). Mannosyl alpha 1-2 linkages in the pyridylamino derivative of Man alpha 1-2 Man alpha 1-6(Man alpha 1-2Man alpha 1-3)Man alpha 1-6(Man alpha 1-2Man alpha 1 2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc were hardly hydrolyzed. Its optimum pH was found to be 7.0. The activity of the enzyme was activated by CO2+, and was potently inhibited by Cu2+, Hg2+, swainsonine, and 1-deoxymannojirimycin. PMID- 1939024 TI - Molecular weight determination of phospholamban oligomer in the presence of sodium dodecyl sulfate: application of low-angle laser light scattering photometry. AB - The number of polypeptides constituting the oligomeric structure of canine phospholamban (a putative regulator of Ca(2+)-ATPase of cardiac sarcoplasmic reticulum) stable even in the presence of sodium dodecyl sulfate was estimated through determination of the molecular weight of the oligomer. Owing to the small molecular size, the low UV-absorptivity and the limited availability, the molecular weight determination required very sophisticated application of the following technique, used as the only recourse: low-angle laser light scattering measurement combined with high-performance gel chromatography. The molecular weight of phospholamban oligomer was found to be 30,400 and the number of subunits was concluded to be five after correction for the dependence of the apparent molecular weights on the protein concentration. PMID- 1939025 TI - Crystallization and main-chain structure of neutral protease from Streptomyces caespitosus. AB - A neutral protease, i.e., a zinc-containing metalloendoprotease from Streptomyces caespitosus, has been crystallized using acetone as a precipitating agent. The crystals diffract to better than 1.5 A resolution when a rotating anode X-ray generator is used as an X-ray source. Protein phase angles were calculated by the multiple isomorphous replacement method using two heavy-atom derivatives (HgCl2 and CH3HgCl). A 6 A resolution electron density map clearly showed molecular boundaries. Although its amino acid sequence is not known, the folding pattern of the polypeptide chain could be traced on a 2.5 A resolution electron density map. A large cleft, which is located on the molecular surface, was proved to be the active site of the enzyme by structure analyses of inhibitor-complex crystals. The highest electron density peak, which corresponds to the cleft, was assigned to a catalytically essential zinc atom on difference Fourier synthesis between native and EDTA-soaked crystals. PMID- 1939026 TI - Differential effects of phospholipids on two similar forms of UDP glucuronyltransferase purified from rat liver and kidney microsomes. AB - Two isoforms of UDP-glucuronyltransferase purified from rat liver (named GT-1) and kidney (named GT-2) have various properties in common but differ in their NH2 terminal sequences. In this study, the two forms were further found to have common immunochemical properties, i.e., they could not be distinguished by Ouchterlony double diffusion and immunoblotting analyses. These isoforms also had the same inducibility as shown by immunoblotting analysis: GT-2 protein in rat was increased by treatment with beta-naphthoflavone and 3-methylcholanthrene, whereas GT-1 was inducible by 3-methylcholanthrene. However, the effects of phospholipids on these enzymes were extremely different. 1-Naphthol glucuronizing activity of GT-1 was increased 7.5-8-fold by lysophosphatidylcholine, but the activity of GT-2 was increased only 3-3.6-fold. The transferase activity of GT-1 toward 4-methylumbelliferone was increased 2-2.5-fold by dilauroylphosphatidylcholine, but that of GT-2 was reduced, while its 4 nitrophenol glucuronidation activity was increased 1.5-fold by the phospholipid. These results indicate that the two similar UDP-glucuronyltransferases from rat liver and kidney interact differently with phospholipids and that the activation level of UDP-glucuronyltransferase activity with phospholipids depends on the aglycone substrates. PMID- 1939027 TI - The primary structure of skeletal muscle myosin heavy chain: I. Sequence of the amino-terminal 23 kDa fragment. AB - Subfragment-1 was prepared from adult chicken pectoralis myosin by limited digestion with alpha-chymotrypsin, and an amino-terminal 23 kDa fragment of the heavy chain was obtained by digesting the subfragment-1 with trypsin. The 205 residue sequence of the fragment was determined by sequencing its cyanogen bromide, tryptic, and chymotryptic peptides. The amino-terminal alpha-amino group of the fragment was acetylated, and two methylated lysines; epsilon-N monomethyllysine and epsilon-N-trimethyllysine were recognized at the 35th and 130th positions, respectively, as in rabbit skeletal myosin. Comparing the 205 residue sequence of the skeletal myosin with those of cardiac, and gizzard myosins from chicken, considerable differences are recognized, especially in the amino-terminal region, but strong homologies are observed around the reactive lysine residue, around the epsilon-N-trimethyllysine residue, and around the consensus sequence of GXXGXGKT for nucleotide-binding proteins. On the other hand, only 12 amino acid substitutions are recognized between adult and embryonic skeletal myosins, allowing for the post-translational methylation. PMID- 1939028 TI - The primary structure of skeletal muscle myosin heavy chain: II. Sequence of the 50 kDa fragment of subfragment-1. AB - The complete amino acid sequence of the 50 kDa fragment of subfragment-1 from adult chicken pectoralis muscle myosin was determined. It contained 431 residues including an epsilon-N-trimethyllysine at position 346. The 431-residue sequence corresponds to the sequence of residues 206 to 639 of chicken embryonic breast muscle myosin heavy chain which was predicted from the nucleotide sequence of the cDNA by Molina et al. [Molina, M. I., Kropp, K.E., Gulick, J., & Robbins, J. (1987) J. Biol. Chem. 262, 6478-6488]. Comparing the two sequences, 23 amino acid substitutions and three deletions/insertions are recognized. PMID- 1939029 TI - The primary structure of skeletal muscle myosin heavy chain: III. Sequence of the 22 kDa fragment and the alignment of the 23 kDa, 50 kDa, and 22 kDa fragments. AB - The amino acid sequence of the 197-residue 22 kDa fragment from chicken pectoralis muscle was determined to be as follows: K-K-G-S-S-F-Q-T-V-S-A-L-F-R-E N-L-N-K-L- M-A-N-L-R-S-T-H-P-H-F-V-R-C-I-I-P-N-E-T-K-T-P-G-A-M-E-H-E-L-V-L-H-Q-L R- C-N-G-V- L-E-G-I-R-I-C-R-K-G-F-P-S-R-V-L-Y-A-D-F-K-Q-R-Y-R-V-L-N-A-S-A-I-P-E-G Q- F-M-D-S- K-K-A-S-E-K-L-L-G-S-I-D-V-D-h-T-Q-Y-R-F-G-H-T-K-V-F-F-K-A-G-L-L-G-L-L E- E-M-R-D- D-K-L-A-E-I-I-T-R-T-Q-A-R-C-R-G-F-L-M-R-V-E-Y-R-R-M-V-E-R-R-E-S-I-F-C I- Q-Y-N-V-R-S-F-M-N-V-K-H-W-P-W-M-K-L-F-F-K, where h stands for 3-N methylhistidine. The amino acid sequences of the 22 kDa fragment and its equivalent fragment from chicken ventricle and gizzard muscle myosins were also determined by our group. Predicted secondary structures of these 22 kDa fragment regions and of the reported chicken embryo myosin revealed some possible structural differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939030 TI - The primary structure of skeletal muscle myosin heavy chain: IV. Sequence of the rod, and the complete 1,938-residue sequence of the heavy chain. AB - In the preceding paper [Maita, T., Miyanishi, T., Matsuzono, K., Tanioka, Y., & Matsuda, G. (1991) J. Biochem. 110, 68-74], we reported the amino-terminal 837 residue sequence of the heavy chain of adult chicken pectoralis muscle myosin. This paper describes the carboxyl terminal 1,097-residue sequence and the linkage of the two sequences. Rod obtained by digesting myosin filaments with alpha chymotrypsin was redigested with the protease at high KCl concentration, and two fragments, subfragment-2 and light meromyosin, were isolated and sequenced by conventional methods. The linkage of the two fragments was deduced from the sequence of an overlapping peptide obtained by cleaving the rod with cyanogen bromide. The rod contained 1,039 amino acid residues, but lacked the carboxyl terminal 58 residues of the heavy chain. A carboxyl-terminal 63-residue peptide obtained by cleaving the whole heavy chain with cyanogen bromide was sequenced. Thus, the carboxyl terminal 1,097-residue sequence of the heavy chain was completed. The linkage of subfragment-1 and the rod was deduced from the sequence of an overlapping peptide between the two which was obtained by cleaving heavy meromyosin with cyanogen bromide. Comparing the sequence of the adult myosin thus determined with that of chicken embryonic myosin reported by Molina et al. [Molina, M.I., Kropp, K.E., Gulick, J., & Robbins, J. (1987) J. Biol. Chem. 262, 6478-6488], we found that the sequence homology is 94%. PMID- 1939033 TI - Strategic planning: a biomedical communications model. AB - This article describes a biomedical communications approach to strategic planning. This model produces a short-term plan that allows a department to take the competitive advantage, react to technological change, and make timely decisions on new courses of action. The model calls for self-study, involving staff in brainstorming sessions where options are identified and ideas are prioritized into possible strategies for success. The article recommends that an evaluation and monitoring schedule be implemented after decisions have been made. PMID- 1939032 TI - Adenosine induces System A amino acid transport in cultured rat hepatocytes. AB - Adenosine caused a 2.5-fold increase in the sodium-dependent uptake of 2 aminoisobutyric acid in rat hepatocytes in primary culture following incubation for 3 h. The range of stimulating concentrations of adenosine corresponded to that of cAMP formation. Adenosine increased the Vmax of the transport without altering the Km for 2-aminoisobutyric acid. These effects of adenosine were abolished by actinomycin D. N6-L-Phenylisopropyladenosine also caused twofold increase in the amino acid transport. These findings suggest that adenosine induces System A amino acid transport in a transcription-dependent manner, and the P1-purinergic receptors are mainly involved in this action of the nucleoside. PMID- 1939031 TI - Kinetics of the hydrolysis of monodispersed and micellar phosphatidylcholines catalyzed by a phospholipase C from Bacillus cereus. AB - The phosphatidylcholine-hydrolyzing phospholipase C, so-called "phospholipase C" (PLC), was isolated from the culture of Bacillus cereus strain IAM 1208. The amino-acid composition and partial N-terminal sequence of the purified enzyme were in good agreement with those expected from the nucleotide sequence for a PLC of strain ATCC 10987 [Johansen et al. (1988) Gene 65, 293-304]. The chain-length dependence of kinetic parameters for the PLC-catalyzed hydrolysis of monodispersed short-chain phosphatidylcholines (diCNPC, N = 3-6) was studied by a pH-stat assay method at 25 degrees C, pH 8.0, and ionic strength 0.2 in the presence of saturating amounts of Zn2+ (0.1 mM). The result was compared with those for snake venom phospholipases A2 [Teshima et al. (1989) J. Biochem. 106, 518-527]. It was found that the interaction of the PLC with the head group of the substrate molecule is very important for the binding. The pH dependences of kinetic parameters for the hydrolysis of monodispersed diC5PC and mixed micelles of diC16PC with Triton X-100 were also studied under the same conditions. An ionizable group, whose pK value is perturbed from 7.77 to 8.30 by substrate binding, was found to be essential to the catalysis. This group was tentatively assigned to His 14 on the basis of the results on X-ray crystallographic and chemical modification studies [Hough et al. (1989) Nature 338, 357-360 and Little (1977) Biochem. J. 167, 399-404].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939034 TI - Videodisc technology trends in the health sciences: revisited. AB - This paper describes a national study to determine levels and kinds of videodisc utilization in health science institutions throughout North America. In the winter of 1989, 922 surveys were mailed to six different health science professional groups; 244 (26%) completed survey forms were returned. A comparison between this survey and one conducted by the authors in 1987 clearly shows that videodisc technology for medical education is varied and expanding within academic health science centers in North America. PMID- 1939035 TI - Leon Schlossberg: a career in retrospect. AB - Featured here is a look at the career of medical illustrator Leon Schlossberg. A charter member of the Association of Medical Illustrators, he was presented the 1990 Lifetime Achievement Award at the 45th Annual AMI meeting in Philadelphia. For over 50 years, Schlossberg has served as illustrator and educator. Through his skillful and precise illustrations, he has contributed greatly to the establishment of the professional protocol for the relationship between the medical illustrator and the surgeon. PMID- 1939036 TI - A quantitative study of the ultrastructure of fibroblasts within the enamel related connective tissue of the rat incisor. AB - A quantitative ultrastructural study was made of the fibroblasts of the enamel related connective tissue and periodontal ligament of the rat incisor. The two populations of fibroblasts were very similar in morphology, the only difference found in the parameters measured being the increased number of microtubules in the enamel-related connective tissue. The data do not lend support to the idea that the fibroblasts of the periodontal ligament generate the eruptive force by their motility or contractility. PMID- 1939037 TI - [A model of an in vitro biological assay controlled by immunofluorescence and scanning electron microscopy]. AB - This study was designed to complete the cell culture test for the cytotoxicity assessment of dental material presented by Christen et al. (1989) and Regad et al. (1989). Two liner materials were selected for this experiment which had already been subjected to both in vivo and in vitro tests. After 2, 7 and 14 days of contact with the test materials, the cell responses were evaluated under the light microscope by their growth pattern and morphological aspects. Cell synthesis of fibronectin and type I and III collagen was studied by immunofluorescence. Surface appearance of the cells in contact with the materials as well as their structures were observed by scanning electron microscopy. This study confirmed the viability of the in vitro cytotoxicity assessment methods with cell cultures. The results also demonstrated the potentials of this method in the early screening of dental materials for their biological compatibility. PMID- 1939038 TI - Targetting the production of monoclonal antibodies to the hemagglutinating adhesin of Bacteroides (Porphyromonas) gingivalis by injection of an immunoprecipitate from crossed immunoelectrophoresis. AB - This study has demonstrated that the production of monoclonal antibodies (MAbs) can be targetted to a predetermined antigen by immunization with the relevant immunoprecipitate (IP) excised from an agarose gel. The target antigen was the hemagglutinating adhesin HA-Ag2 of Bacteroides (Porphyromonas) gingivalis precipitated from a crude antigen extract with a rabbit antiserum in crossed immunoelectrophoresis. The immunization protocol used included: subcutaneous injection of 1 IP in Freund's complete adjuvant to Balb/c mice on day 0 and of 0.5 IP on day 8, followed by an intravenous booster injection of outer membranes on day 15, 4 days before the fusion. Of the 9 MAbs obtained, 8 were specific for HA-Ag2 since they reacted with its characteristic electrophoretic bands at 43 and 49 kDa. The ninth MAb was specific for the B. gingivalis lipopolysaccharide. The method allows for easy obtention of MAbs of predetermined specificity without purification of the antigen. PMID- 1939039 TI - [The transmission of Actinobacillus actinomycetemcomitans between spouses]. AB - The aim of this investigation was to study the transmission of Actinobacillus actinomycetemcomitans (A.a) between husband and wife when one of them was affected by acute juvenile periodontitis (P.A.J.). The hypothesis tested was the role played by the reservoir of the non-infected partner in explaining the frequent recurrences of the disease in the affected spouse despite combined antibiotherapeutical and surgical treatments. Twenty subjects with P.A.J. were studied. A.a. was found in the sub-gingival flora of nineteen of them. This micro organism was also isolated in each of the partners of the nineteen patients. Each couple presented strains of the same biotype. The serotypes were studied in seven of these couples and confirmed the results of the biotypes. All theses results are in favour of the transmission of A.a. between partners. PMID- 1939040 TI - Toothbrushing with the root of Euclea natalensis. AB - The custom of cleaning teeth and the gums with a chewed root of the tree Euclea natalensis, in the belief that it benefits oral health, is practised in South Africa by married women of an African Zanzibari community. The root of E. natalensis contains naphthoquinones which are bactericidal and, as they are also pigments, the mouths of the root users are stained bright orange. Samples of fresh root were tested against Streptococcus mutans and organisms in saliva and from deep periodontal pockets. Aerobic as well as anaerobic bacterial growth was suppressed in all instances. In addition we compared the plaque index (Silness et Loe), the periodontal index (CPITN), the DMFT and the state of the oral mucosa of root users and non-users. No significant differences were recorded in any of the variables. Although the beneficial effects claimed for this custom may have scientific validity, it is concluded that the daily practice is too limited to have a demonstrable beneficial effect. PMID- 1939041 TI - [A clinical and histological study of the efficacy of betadine on gingival inflammation]. AB - 12 patients (7 men and 5 women) with advanced periodontitis and probing depths of 4mm or more were selected to assess the effectiveness of an antiseptic: betadine used in situ, as a subgingival irrigation in periodontal pockets. Although widely used in other fields of medicine such as gynecology and dermatology, betadine has not been used in periodontology. However, betadine is an excellent antiseptic with a wide range of action. The slow release of iodine explains why this antiseptic is well tolerated by mucosae. The oral cavity was divided in 2 parts: the left side was irrigated with betadine while the right side was irrigated with saline which was used as a control. Irrigations were performed once a day during a period of 15 days. Patients were able to carry out the irrigations themselves after careful, instruction. Thc practitioner carried out the irrigation on day 0 and day 8. The comparison of clinical and histological data showed a decrease in gingival inflammation after 15 days of treatment. By means of the Student "t" test significant decreases in the plaque index, the gingival, index and the bleeding index were observed between day 0 and day 15 as well as a significant increase in recession. These clinical results were correlated with histological findings. Significant decreases in the volumetric density of the infiltrated connective tissue, the non collagenous structures and the number of plasma cells were observed as well as significant increases in the volumetric density of the non-infiltrated connective tissue of the collagenous structures and the number of fibroblasts. PMID- 1939042 TI - The effect of topical vitamin C on palatal oral mucosal carcinogenesis using 4 nitroquinoline-1-oxide. AB - Vitamin C is an essential nutrient whose protective influence in carcinogenesis has been reported frequently. In general, evidence suggests that vitamin C inhibits the formation of some carcinogens and decreases the incidence and delays the onset of neoplastic lesions but the mechanisms by which this occurs are not known. In 1973, Wallenius and Lekholm induced intra-oral palatal squamous cell carcinomas by the use of the water soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) applied thrice weekly to the palatal mucosa of rats. The aim of this study was to determine if in rats topically applied vitamin C had an effect on the process of carcinogenesis caused by the application of 4NQO. The results of this study showed that in the 4NQO treated animals a progression through mild, moderate and severe dysplasia occurred prior to neoplastic changes at 24 weeks and that this progression was delayed in the animals treated topically with vitamin C. It can be concluded that topically applied vitamin C has a modulating effect on the neoplastic process induced by 4NQO in the palatal mucosa of rats. PMID- 1939043 TI - The healing of cranial defects by demineralized osseous implants: a radiographic, histological and radioisotope-uptake study in rats. AB - The purpose of this study was to evaluate by different techniques the healing effect of demineralized allogeneic bone in parietal cranial defects in rats. 45Ca incorporation was measured for nine consecutive weeks in groups of control and implanted rats. Repeated 99mTc MDP uptake measurements were performed for nine weeks on the same group of rats. Each measurement was preceded by a cranial radiography. At the end of the study the animals were sacrificed for histologic evaluation. The results of the 45Ca incorporation, 99mTc MDP uptake measurements and the histologic pictures confirmed the osteogenic capacity of demineralized allogenic bone. From the results it can concluded that 99mTc MDP uptake measurements are a powerful tool in the evaluation of the healing process. It can be utilized sequentially in the same animal and gives detailed information about the progress of osteogenic activity over the entire implant area. PMID- 1939044 TI - [The distribution and prevalence of Haemophilus actinomycetemcomitans in the oral cavity]. AB - The prevalence and distribution of Haemophilus actinomycetemcomitans (H.a.) were studied in 3292 specimens of subgingival plaque on the four subgingival aspects of all teeth of the dental arch, 150 specimens from the mucosal surface (tongue and cheek) and 30 saliva specimens in 30 subjects. The sample population of 30 subjects was subdivided into three groups: 10 normal subjects, 10 subjects with localised juvenile periodontitis (SLJP) and 10 subjects with adult chronic periodontitis (SACP). The prevalences of H.a. in subgingival areas of each group mentioned were 30%, 90% and 60% respectively. Scores for prevalence obtained with other types of specimens proved to be lower except for saliva specimens which appear to be a less representative marker of subgingival prevalence of H.a.. Histograms for the distribution of H.a. revealed a predominance of this microorganism on the proximal surface of molar teeth in the three groups of patients. Only the SLJP also exhibited a high prevalence on the proximal aspect of the incisor teeth. The wide distribution of H.a. in all of the clinical groups studied suggests that this bacterium is not a good marker of periodontal disease and that it is necessary to define the most characteristic phenotypes and genotypes. PMID- 1939045 TI - [A comparative study of the in vitro biocompatibility of 2 root canal sealing cements]. AB - The aim of this study was to evaluate the biocompatibility of radicular sealing cements with agarose cell culture. The two cements studied were Sealite and Pulp Canal Sealer with different mixing times. In the experimental conditions used the cytocompatibility of Sealite was better than that of Pulp Canal Sealer. The cytotoxicity of both products was not negligible and corresponded to those of other studies with Pulp Canal Sealer and a cement with amount similar composition to Sealite. Because theses cements are currently used with success in humans, the results of this test raise the question of extrapolation to man. PMID- 1939047 TI - Survival of Prevotella intermedia (Bacteroides intermedius) in transport media. AB - Five transport media were selected for testing, in vitro, the survival of a pure strain of Prevotella intermedia (Bacteroides intermedius) for 6, 24, and 72 hours. Two were non-nutrient transport media (RTF and VMG IV). The three others (TG, PY, PYG) were nutrient media. An increase in the transport time, and manipulations in an aerobic atmosphere compromised the survival of the bacteria. PY ensured good survival of the bacteria. RTF seems to be the best medium for the transport of P. intermedia, when quantitative analysis is required. PMID- 1939046 TI - Effect of sodium lauryl sulfate on the uptake of fluoride from NaF and MFP by etched enamel in vitro. AB - Melsen and Rolla (1983) have previously shown that sodium lauryl sulfate may reduce the cariostatic effect of fluoride when present together with sodium monofluorophosphate during topical application. The aim of the present study was to examine the in vitro deposition of fluoride on etched enamel during topical application with sodium fluoride in combination with sodium lauryl sulfate. In addition, uptake by etched enamel of fluoride sodium monofluorophosphate in combination with sodium lauryl sulfate was examined. It was found that sodium lauryl sulfate decreased the amount of fluoride taken up by the enamel. PMID- 1939048 TI - Surface studies on titanium IMZ implants. AB - The aim of this study was to investigate the surface feature of the IMZ implant. Eight non-implanted new samples and four implanted samples removed one year after insertion were prepared. The 8 non-implanted samples were divided into two groups. The first group was sterilized and the second group was manipulated by bare hands. The implanted samples underwent a careful procedure to recover the metal surface. Then, both the non-implanted new samples and implanted samples were subjected to X-ray electron spectroscopy (XPS) and Rutherford back scattering spectroscopy (KBS) analyses. Subsequently, all the samples were subjected to scanning electron microscopic (SEM) examination, and surface roughness and profilometric measurements. The SEM photomicrograph showed a rough surface composed of fused granular metal separated by gaps. Sometimes the presence of isolated well-shaped granules of 0.8-1.8 microns in diameter was observed. This structure was related to the manufacturing process of the IMZ implant. The implanted surfaces showed no intergranular gaps and appeared less rough (average roughness: Ra = 1.91 +/- 0.1 microns) compared with the new non implanted surfaces (Ra = 4.93 +/- 0.3). XPS analysis at a maximum resolution depth of 1.5 nm revealed TiO2, C, O compounds on sterilized non-implanted surfaces. The hand-handled non-implanted surfaces on the contrary did not show TiO2 due to contamination. The elements Ca, C, O and N were found on the one-year implanted IMZ surfaces; TiO2, however, was absent. RBS analysis at a maximum resolution depth of 1000 nm, indicated a decrease of the total thickness of TiO2 after one year of IMZ implantation. The TiO2 thickness was 0.5-0.7 microns for the non-implanted new IMZ surfaces and 0.03-0.2 microns for implanted IMZ surfaces. PMID- 1939050 TI - Structural features in eukaryotic mRNAs that modulate the initiation of translation. PMID- 1939049 TI - Intratubular crystal deposition and remineralization of carious dentin. AB - An analysis of accumulated experimental results, the mechanism of intratubular crystal deposition in the transparent layer and remineralization of the matrix of carious dentin has led to a more rounded concept and understanding of dentin caries relevant to clinical practice. The transparent layer of carious dentin is not sclerotic but is part of the demineralized softened dentin. The crystal precipitation in the tubules is an intermediate product in a slow demineralization process. Physiological remineralization occurs in matrix of the inner carious dentin which has crossbanded collagen fibers and odontoblastic processes. The overall process of dentin caries is re-examined and described in view of these concepts. PMID- 1939051 TI - Identification of a cis-acting sequence in the collagen II enhancer required for chondrocyte expression and the binding of a chondrocyte nuclear factor. AB - Collagen II is synthesized at high levels by differentiated chondrocytes. A 620 base pair DNA sequence in the first intron of the rat collagen II gene was previously determined to have chondrocyte-specific enhancer activity. Using mobility shift assays, we have defined a decamer sequence, 5'-CACAATGCAT-3', in the middle of the enhancer that binds a protein or protein complex expressed by chondrocytes but not by NIH3T3 cells or L2 rat fibroblasts. This protein was also induced during the differentiation of limb bud mesenchymal cells into chondrocytes. Mutational analyses, coupled with both in vitro binding studies and direct assays of enhancer activity following transfection into cells, demonstrated that this sequence is involved in the binding of the chondrocyte nuclear protein(s) and is necessary for the enhancer activity. This sequence has homology to the consensus binding sequence for helix-loop-helix transcription factors. PMID- 1939052 TI - Mitochondrial phosphate transport. The Saccharomyces cerevisiae (threonine 43 to cysteine) mutant protein explicitly identifies transport with genomic sequence. AB - The yeast mitochondrial phosphate transport protein (PTP) has only 38% sequence similarity to the bovine heart protein, and it has recently been postulated to code for a mitochondrial import receptor. Since the reconstitutively active protein is not completely pure, it is important to demonstrate explicitly that the yeast gene codes for PTP. We have replaced Thr43 with Cys (T43C) and show that its unidirectional and pH gradient-dependent inorganic phosphate transport activity becomes highly sensitive to N-ethylmaleimide. This new PTP/T43C catalyzes less than 10% of the wild type transport activity (1 mM [Pi]e, pHe (6.80); 0 mM [Pi]i, pHi (8.07); 30 s [Pi] uptake) suggesting that Thr43 occupies an important position in the PTP. PMID- 1939053 TI - Trimethoprim binds in a bacterial mode to the wild-type and E30D mutant of mouse dihydrofolate reductase. AB - Previous crystallographic studies of the antibacterial trimethoprim in complexes with bacterial and avian dihydrofolate reductases have shown substantial differences in the mode of binding, providing plausible explanations for the origin of the remarkable species selectivity of this inhibitor (Matthews, D. A., Bolin, J. T., Burridge, J. M., Filman, D. J., Volz, K. W., Kaufman, B. T., Beddell, C. R., Champness, J. N., Stammers, D. K., and Kraut, J. (1985) J. Biol. Chem. 260, 381-391; Matthews, D. A., Bolin, J. T., Burridge, J. M., Filman, D. J., Volz, K. W., and Kraut, J. (1985) J. Biol. Chem. 260, 392-399). A major species difference between the active sites is that the only carboxylate present is always Glu in vertebrates and Asp in bacteria. Crystallographic studies of the wild-type and E30D mutant of the enzyme from mouse now reveal that in both cases trimethoprim is bound in an identical fashion to that observed with the bacterial enzyme, and there is no obvious single explanation for the origin of the 10(5) fold selectivity of trimethoprim binding. In an earlier study of a mouse wild type enzyme using more limited data it was proposed that trimethoprim bound in the avian mode (Stammers, D. K., Champness, J. N., Beddell, C. R., Dann, J. G., Eliopoulos, E. E., Geddes, A. J., Ogg, D., and North, A. C. T. (1987) FEBS Lett. 218, 178-184), but a re-examination indicates that the occupancy of the active site by trimethoprim is less than had been thought, and we are currently unable to make an unambiguous interpretation of the electron density maps and cannot confirm the avian mode of binding in those crystals. PMID- 1939054 TI - Aromatase mRNA in the extragonadal tissues of chickens with the henny-feathering trait is derived from a distinctive promoter structure that contains a segment of a retroviral long terminal repeat. Functional organization of the Sebright, Leghorn, and Campine aromatase genes. AB - The henny-feathering trait is an autosomal dominant mutation that causes the expression of aromatase activity and accumulation of aromatase mRNA in extragonadal tissues of chickens. The current studies establish that the aromatase gene is not amplified and is organized similarly in control (Leghorn) and henny-feathered (Sebright and Campine) birds. Nucleotide sequence analysis of the nine coding exons of the aromatase gene reveals that the predicted amino acid sequence is identical in all three strains. We, therefore, characterized the genomic DNA segments flanking the coding segment of the Sebright, Leghorn, and Campine aromatase genes. The site of transcription initiation utilized in the ovary of all three strains is located approximately 147 nucleotides upstream of the initiator methionine. In addition to aromatase mRNA derived from this common ovarian promoter, another species of aromatase mRNA is present in Sebright and Campine ovary and is the only type detected in Sebright fibroblasts. cDNA copies of this second species of aromatase mRNA contain a unique 5' terminus, suggesting that a second promoter controls extragonadal aromatase expression in birds that carry the henny-feathering trait. Nucleotide sequence analysis of this 5' terminus indicates that this segment is derived from a retroviral long terminal repeat. PMID- 1939056 TI - Characterization of a mutation affecting the function of Escherichia coli folylpolyglutamate synthetase-dihydrofolate synthetase and further mutations produced in vitro at the same locus. AB - The folC gene from mutant strain SF4 was cloned into a pUC19 plasmid. Expression of the mutant gene from the lac promoter of the plasmid complemented the auxotrophy for methionine of the SF4 strain. The only difference in sequence between the mutant and wild-type genes was a G925A base change resulting in an A309T amino acid change. The mutant enzyme had a 30-fold higher Km for 10 formyltetrahydrofolate as well as a 60-fold higher Km for glutamate and a 200 fold higher Km for dihydropteroate of the dihydrofolate synthetase activity. Site specific mutagenesis was used to substitute other amino acids at codon 309. Mutants with glycine, isoleucine, and valine substitutions at this position, when expressed from multicopy plasmids, complemented the SF4 strain. The glycine mutant had properties similar to the wild-type enzyme, whereas the isoleucine and valine mutants had properties similar to the threonine mutant, SF4. Mutant genes with arginine, glutamate, and leucine substitutions, which did not complement the SF4 strain, could complement a folC deletion strain, but produced smaller colonies on complex plates and did not grow on minimal medium. In the deletion strain, an increasing requirement for folate product supplements was observed as the folylpolyglutamate synthetase-dihydrofolate synthetase activities of the complementing mutants decreased. PMID- 1939055 TI - The high and low affinity transport systems for dipeptides in kidney brush border membrane respond differently to alterations in pH gradient and membrane potential. AB - The principal aim of the present study was to investigate the effects of variation in proton gradient and membrane potential on the transport of glycyl-L glutamine (Gly-Gln) by renal brush border membrane vesicles. Under our conditions of transport assay, Gly-Gln was taken up by brush border membrane vesicles almost entirely as intact dipeptide. This uptake was mediated by two transporters shared by other dipeptides and characterized as the high affinity (Kt = 44.1 +/- 11.2 microM)/low capacity (Vmax = 0.41 +/- 0.03 nmol/mg protein/5 s) and low affinity (Kt = 2.62 +/- 0.50 mM)/high capacity (Vmax 4.04 +/- 0.80 nmol/mg protein/5 s) transporters. In the absence of a pH gradient, only the low affinity system was operational, but with a reduced transport capacity. Imposing a pH gradient of 1.6 pH units increased the Vmax of both transporters. Kinetic analysis of the rates of Gly-Gln uptake as a function of external pH revealed Hill coefficients of close or equal to 1, indicating that transporters contain only one binding site for the interaction with external H+. The effects of membrane potential on Gly Gln uptake were investigated with valinomycin-induced K+ diffusion potentials. The velocity of the high affinity system but not of the low affinity system increased linearly with increasing inside-negative K+ diffusion potentials (p less than 0.01). The Kt of neither system was affected by alterations in either pH gradient or membrane potential. We conclude that (a) the high affinity transporter is far more sensitive to changes in proton gradient and membrane potential than the low affinity transporter and (b) in the presence of a pH gradient, transport of each dipeptide molecule requires cotransport of one hydrogen ion to serve as the driving force. PMID- 1939057 TI - Phosphorylation by cdc2 kinase modulates DNA binding activity of high mobility group I nonhistone chromatin protein. AB - Chromatin high mobility group protein I (HMG-I) is a mammalian nonhistone protein that has been demonstrated both in vitro and in vivo to preferentially bind to A.T-rich sequences of DNA. Recently the DNA-binding domain peptide that specifically mediates the in vitro interaction of high mobility group protein (HMG)-I with the narrow minor groove of A.T-DNA has been experimentally determined. Because of its predicted secondary structure, the binding domain peptide has been called "the A.T hook" motif. Previously we demonstrated that the A.T hook of murine HMG-I protein is specifically phosphorylated by purified mammalian cdc2 kinase in vitro and that the same site(s) are also phosphorylated in vivo in metaphase-arrested cells. We also found that the DNA binding affinity of short synthetic binding domain peptides phosphorylated in vitro by cdc2 kinase was significantly reduced compared with unphosphorylated peptides. Here we extend these findings to intact natural and recombinant HMG-I proteins. We report that the affinity of binding of full-length HMG-I proteins to A.T-rich sequences is highly dependent on ionic conditions and that phosphorylation of intact proteins by cdc2 kinase reduces their affinity of in vitro binding to A.T-DNA by about 20 fold when assayed near normal mammalian physiological salt concentrations. Furthermore, in cell synchronization studies, we demonstrated that murine HMG-I proteins are phosphorylated in vivo in a cell cycle-dependent manner on the same amino acid residues modified by purified cdc2 kinase in vitro. Together these results strongly support the assertion that HMG-I proteins are natural substrates for mammalian cdc2 kinase in vivo and that their cell cycle-dependent phosphorylation by this enzyme(s) significantly modulates their DNA binding affinity, thereby possibly altering their biological function(s). PMID- 1939058 TI - Iron oxidation chemistry in ferritin. Increasing Fe/O2 stoichiometry during core formation. AB - The origin of previously observed variations in stoichiometry of iron oxidation during the oxidative deposition of iron in ferritin has been poorly understood. Knowledge of the stoichiometry of Fe(II) oxidation by O2 is essential to establishing the mechanism of iron core formation. In the present work, the amount of Fe(II) oxidized was measured by Mossbauer spectrometry and the O2 consumed by mass spectrometry. The number of protons produced in the reaction was measured by "pH stat" titration and hydrogen peroxide production by the effect of the enzyme catalase on the measured stoichiometry. For protein samples containing low levels of iron (24 Fe(II)/protein) the stoichiometry was found to be 1.95 +/- 0.18 Fe(II)/O2 with H2O2 being a product, viz. Equation 1. 2Fe2+ + O2 + 4H2O--- 2FeOOH + H2O2 + 4H+ (1) EPR spin trapping experiments showed no evidence of superoxide radical formation. The stoichiometry markedly increased with additional iron (240-960 Fe/protein), to a value of 4 Fe(II)/O2 as in Equation 2. 4Fe2+ + O2 + 6H2O----4FeOOH + 8H+ (2) As the iron core is progressively laid down, the mechanism of iron oxidation changes from a protein dominated process with H2O2 being the primary product of O2 reduction to a mineral surface dominated process where H2O is the primary product. These results emphasize the importance of the apoferritin shell in facilitating iron oxidation in the early stage of iron deposition prior to significant development of the polynuclear iron core. PMID- 1939059 TI - Phosphorylation of caldesmon by p34cdc2 kinase. Identification of phosphorylation sites. AB - It has recently been shown that caldesmon from non-muscle (Yamashiro, S., Yamakita, Y., Hosoya, H., and Matsumura, F. (1991) Nature 349, 169-172) and smooth muscle cells (Mak, A. S., Watson, M. H., Litwin, C. M. E., and Wang, J. H. (1991) J. Biol. Chem. 266, 6678-6681) can be phosphorylated in vitro by p34cdc2 kinase resulting in the inhibition of caldesmon binding to F-actin and Ca(2+) calmodulin. In this study, we have identified five phosphorylation sites in smooth muscle caldesmon at Ser582, Ser667, Thr673, Thr696, and Ser702. All the sites bear some resemblance to the S(T)-P-X-X motif recognized by p34cdc2. The preferred site of phosphorylation at Thr673 accounts for about 40% of the total phosphorylation. Four of the sites occur in two pairs of closely spaced sites, Ser667/Thr673 and Thr696/Ser702; phosphorylation of one site in each pair inhibits strongly the phosphorylation of the second site in the same pair, presumably due to the close proximity of the two sites. Similar negative cooperativity in phosphorylation of Ser667 and Thr673 was observed using a 22 residue synthetic peptide containing the two sites. Phosphorylation of Ser667/Thr673 and Thr696/Ser702 account for about 90% of the total level of phosphorylation and these sites are located within the 10-kDa CNBr fragment at the COOH-terminal end of caldesmon known to bind actin and Ca(2+)-calmodulin. PMID- 1939060 TI - NADPH-cytochrome P-450 oxidoreductase. The role of cysteine 566 in catalysis and cofactor binding. AB - Site-directed mutagenesis was employed to investigate the role of Cys566 in the catalytic mechanism of rat liver NADPH-cytochrome P-450 oxidoreductase. Rat NADPH cytochrome P-450 oxidoreductase and mutants containing either alanine or serine at position 566 were expressed in Escherichia coli and purified to homogeneity. Substitution of alanine at position 566 had no effect on enzymatic activity with the acceptors cytochrome c and ferricyanide but did increase trans-hydrogenase activity with 3-acetylpyridine adenine dinucleotide phosphate by 79%. The Km for NADPH was increased 2.5-fold, and the NADP+ KI was increased 4.8-fold compared with that found for the wild-type enzyme. The conservative substitution, Ser566, produced a 50% decrease in cytochrome c reductase activity whereas activity with ferricyanide was decreased 57%, and 3-acetylpyridine adenine dinucleotide phosphate activity was unaffected. The NADPH Km was increased 4.6-fold, and the NADP+ KI increased 7.6-fold. The dependence of cytochrome c reductase activity on the KCl concentration was markedly altered by the Cys566 substitutions. Maximum activity for the wild-type enzyme was observed at approximately 0.18 M KCl whereas maximum activity for the mutant enzymes was observed between 0.04 and 0.09 M KCl. The pH dependence of cytochrome c reductase activity, cytochrome c Km, and flavin content were unaffected by these substitutions. These results demonstrate that Cys566 is not essential for activity of rat liver NADPH cytochrome P-450 oxidoreductase although the cysteine side chain does affect the interaction of NADPH with the enzyme. PMID- 1939061 TI - Inactivation of dihydropyrimidine dehydrogenase by 5-iodouracil. AB - 5-Iodouracil was a substrate for bovine liver dihydropyrimidine dehydrogenase (DHPDHase) and was a potent inactivator of the enzyme. NADPH increased the rate of inactivation and thymine protected against inactivation. These findings suggest that 5-iodouracil was a mechanism-based inactivator. However, dithiothreitol and excess 5-iodouracil protected the enzyme against inactivation. Thus, a reactive product, presumably 5-iodo-5,6-dihydrouracil generated through the enzymatic reduction of 5-iodouracil, was released from DHPDHase during processing of 5-iodouracil. Since only 18% of [6-3H]5-iodouracil reduced by DHPDHase was covalently bound to the enzyme and radiolabel was not lost to the solvent as tritium, the partition coefficient for inactivation was 4.5. However, the enzymatic activity was completely titrated with 1.7 mol of 5-iodouracil per mol of enzyme-bound flavin. These results indicate that there was 0.31 mol of enzyme-bound inactivator per mol of enzyme flavin. This suggests there were 3.2 flavins per active site, which is consistent with the report of multiple flavins per enzymic subunit (Podschun, B., Wahler, G., and Schnackerz, K. D. (1989) Eur. J. Biochem. 185, 219-224). DHPDHase was inactivated by 2.1 mol of racemic 5-iodo 5,6-dihydrouracil per mol of active sites. The stoichiometry for inactivation of the enzyme by the nonenzymatically generated enantiomer of 5-iodo-5,6 dihydrouracil was calculated to be 1. Two radiolabeled fragments were isolated from a tryptic digest of DHPDHase inactivated with radiolabeled 5-iodouracil. The amino acid sequences of these peptides were Asn-Leu-Ser-X-Pro-His and Asn-Leu-Ser X-Pro-His-Gly-Met-Gly-Glu-Arg where X was the modified amino acid containing radiolabel from [6-3H]5-iodouracil. Fast atom bombardment mass spectral analysis of the smaller peptide yielded a protonated parent ion mass of 782 daltons that was consistent with X being a S-(hexahydro-2,4-dioxo-5-pyrimidinyl)cysteinyl residue. PMID- 1939063 TI - Primary structure of rat ribosomal protein S2. A ribosomal protein with arginine glycine tandem repeats and RGGF motifs that are associated with nucleolar localization and binding to ribonucleic acids. AB - The amino acid sequence of the rat 40 S ribosomal subunit protein S2 was deduced from the sequence of nucleotides in two recombinant cDNAs and confirmed from the amino acid sequence of a cyanogen bromide peptide obtained from the protein. Ribosomal protein S2 has 293 amino acids and has a molecular weight of 31,211. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 23-28 copies of the S2 gene. The mRNA for the protein is about 1,000 nucleotides in length. The highly conserved repetitive mammalian gene family designated LLRep3, but not identified before, encodes ribosomal protein S2. Rat S2 is related to Saccharomyces cerevisiae S4, Methanococcus vannielii S5, Escherichia coli S5, and other members of the prokaryotic S5 family. S. cerevisiae S4 and E. coli S5 are involved in the binding of aminoacyl-tRNA to ribosomes and in conditioning the fidelity of translation; it is plausible to assume that rat S2 serves similar functions. The NH2-terminal region of S2 is rich in arginine-glycine repeats including eight that occur in tandem and has two consecutive copies of the motif RGGF; these sequences have been associated with nucleolar localization and binding to RNA. PMID- 1939062 TI - The interaction of caldesmon with the COOH terminus of actin. AB - Caldesmon interacts with the NH2-terminal region of actin. It is now shown in airfuge centrifugation experiments that modification of the penultimate cysteine residue of actin significantly weakens its binding to caldesmon both in the presence and absence of tropomyosin. Furthermore, as revealed by fluorescence measurements, caldesmon increases the exposure of the COOH-terminal region of actin to the solvent. This effect of caldesmon, like its inhibitory effect on actomyosin ATPase activity, is enhanced in the presence of tropomyosin. Proteolytic removal of the last three COOH-terminal residues of actin, containing the modified cysteine residue, restores the normal binding between caldesmon and actin. These results establish a correlation between the binding of caldesmon to actin and the conformation of the COOH-terminal region of actin and suggest an indirect rather than direct interaction between caldesmon and this part of actin. PMID- 1939064 TI - Bovine heart microsomes contain an Mr = 66,000 non-heme iron protein which stimulates NADPH oxidation. AB - Bovine heart microsomes have been found to contain a non-heme iron protein which serves as an electron acceptor for NADPH-cytochrome P-450 reductase and therefore stimulates NADPH oxidation. This protein, tentatively referred to as Microsomal Iron Protein (MIP), has been extracted with Triton N-101 and purified by ion exchange chromatography on CM- and DEAE-celluloses and gel filtration on Sepharose 6B. MIP is an Mr = 66,000 monomer with 17 atoms of Fe(III)/molecule. Incubation with dithionite removes iron from MIP and abolishes the stimulation of NADPH oxidation, but subsequent incubation with nitrilotriacetic-Fe(III) reincorporates iron and restores the stimulation of NADPH oxidation. Oxygen is the ultimate electron acceptor. In the presence of oxygen, the enzymatic reduction of MIP Fe(III) is followed by the reoxidation of Fe(II) at the expense of oxygen, generating superoxide anion and regenerating MIP Fe(III) for the continuous oxidation of NADPH. In the absence of oxygen, electron transfer from the reductase to MIP Fe(III) causes the release of Fe(II), which limits the ability of MIP to serve as an electron acceptor and stimulate NADPH oxidation. The--NH2-terminal of MIP has been sequenced, and no homology has been found with the sequence of other iron storage or transport proteins such as ferritin or transferrin. PMID- 1939065 TI - Identification of lamin B2 as a substrate of protein kinase C in BALB/MK-2 mouse keratinocytes. AB - Protein phosphorylation by activation of protein kinase C was examined using quiescent cultures of the mouse epidermal keratinocyte line BALB/MK-2. Treatment with phorbol ester caused rapid phosphorylation of five proteins with molecular weights of 80,000, 70,000, 40,000, 34,000, 28,000. Of these proteins, the 70,000 molecular weight one (p70) was studied further. Its position on two-dimensional gel suggested that p70 is nuclear envelope lamin B. This possibility was confirmed by the co-migration of p70 with the lamin fraction of mouse liver and its immunoprecipitation with antinuclear lamina antibody. The lamin B fraction consists of lamin B1 and lamin B2. Evidence that p70 is lamin B2 was obtained by peptide mapping and amino acid sequencing. Lamin B2 is the only lamin that shows a substantial increase in phosphorylation on treatment of BALB/MK-2 cells with phorbol ester. PMID- 1939066 TI - The T4 DNA polymerase accessory proteins form an ATP-dependent complex on a primer-template junction. AB - The DNA polymerase holoenzyme of bacteriophage T4 contains, besides the DNA polymerase itself (the gene 43 protein), a complex of the protein products of T4 genes 44 and 62 (a DNA-dependent ATPase) and of gene 45. Together, the 44/62 and 45 proteins form an ATP-dependent "sliding clamp" that holds a moving DNA polymerase molecule at the 3' terminus of a growing DNA chain. We have used a unique DNA fragment that forms a short hairpin helix with a single-stranded 5' tail (a "primer-template junction") to map the binding sites for these polymerase accessory proteins by DNA footprinting techniques. In the absence of the DNA polymerase, the accessory proteins protect from DNase I cleavage 19-20 nucleotides just behind the 3' end of the primer strand and 27-28 nucleotides on the complementary portion of the template strand. Detection of this DNA-protein complex requires the 44/62 and 45 proteins plus the nonhydrolyzable ATP analogue adenosine 5'-O-(thiotriphosphate). The complex is not detected in the presence of ATP. We suggest that ATP hydrolysis by the 44/62 protein normally activates the accessory proteins at a primer-template junction, permitting the DNA polymerase to bind and thus form the complete holoenzyme. However, when the polymerase is missing, as in these experiments, ATP hydrolysis is instead followed by a release (or loosening) of the accessory protein complex. PMID- 1939067 TI - DNA footprinting studies of the complex formed by the T4 DNA polymerase holoenzyme at a primer-template junction. AB - We have used DNA footprinting techniques to analyze the interactions of five DNA replication proteins at a primer-template junction: the bacteriophage T4 DNA polymerase (the gene 43 protein), its three accessory proteins (the gene 44/62 and 45 proteins), and the gene 32 protein, which is the T4 helix-destabilizing (or single-stranded DNA-binding) protein. The 177-nucleotide-long DNA substrate consisted of a perfect 52-base pair hairpin helix with a protruding single stranded 5' tail. As expected, the DNA polymerase binds near the 3' end of this molecule (at the primer-template junction) and protects the adjacent double stranded region from cleavage. When the gene 32 protein binds to the single stranded tail, it reduces the concentration of the DNA polymerase required to observe the polymerase footprint by 10-30-fold. Periodic ATP hydrolysis by the 44/62 protein is required to maintain the activity of the DNA polymerase holoenzyme (a complex of the 43, 44/62, and 45 proteins). Footprinting experiments demonstrate the formation of a weak complex between the DNA polymerase and the gene 45 protein, but there is no effect of the 44/62 protein or ATP on this enlarged footprint. We propose a model for holoenzyme function in which the complex of the three accessory proteins uses ATP hydrolysis to keep a moving polymerase tightly bound to the growing 3' end, providing a "clock" to measure polymerase stalling. PMID- 1939068 TI - Chemistry of the inactivation of 4-aminobutyrate aminotransferase by the antiepileptic drug vigabatrin. AB - The chemical modification of pig liver 4-aminobutyrate aminotransferase by the antiepileptic drug 4-aminohex-5-enoate (Vigabatrin) has been studied. After inactivation by 14C-labeled Vigabatrin, the enzyme was digested with trypsin, and automated Edman degradation of the purified labeled peptide gave the sequence FWAHEHWGLDDPADVMTFSKK. Chymotryptic digestion of the tryptic peptide and sequencing of a resulting tripeptide identified the penultimate lysine residue of this peptide as the site of covalent modification. This lysine normally binds the coenzyme. Absorption spectroscopy demonstrated the absence of coenzyme from the tryptic peptide, and mass spectrometry showed its mass/charge ratio to be increased by 128. All of the bound coenzyme released after denaturation of the inactivated enzyme was as pyridoxamine phosphate. The structural nature of the modification is deduced, and mechanisms for its occurrence identified. Initially, 1 mol of radiolabeled inhibitor was bound per mol of monomer of the enzyme, although approximately half was released during denaturation and digestion, while the remainder was irreversibly bound. Coenzyme not released as pyridoxamine phosphate retained the absorbance characteristics of the aldimine, although the enzyme was completely inactive. Mass spectrometry of the sample of purified radiolabeled tryptic peptide revealed the presence of an approximately equal amount of a second fragment that contained no modification and from which the second lysine was absent, indicating that at the time of proteolysis the active site lysine was unaltered in 50% of the enzyme molecules. PMID- 1939069 TI - Suppression of Ca2+ oscillations in cultured rat hepatocytes by chemical hypoxia. AB - The model of "chemical hypoxia" with KCN plus iodoacetic acid mimics the ATP depletion and reductive stress of hypoxia. Here, we examined the effects of chemical hypoxia on cytosolic free Na+ and Ca2+ in single cultured rat hepatocytes by multiparameter digitized video microscopy and ratio imaging of sodium-binding furan indicator (SBFI) and Fura-2. Intracellular Na+ increased from about 10 mM to more than 100 mM after 20 min of chemical hypoxia, whereas cytosolic free Ca2+ remained virtually unchanged. In normoxic hepatocytes, phenylephrine (50 microM) and Arg-vasopressin (20-40 nM) induced Ca2+ oscillations in 70 and 40% of cells, respectively. These Ca2+ oscillations were suppressed after one spike following the onset of chemical hypoxia. Phenylephrine and vasopressin also increased inositol phosphate formation by 22 and 147%, respectively. This effect was suppressed by KCN plus iodoacetate. Intracellular acidosis is characteristic of chemical hypoxia. Intracellular acidosis induced by 40 mM Na-acetate suppressed Ca2+ oscillations but did not inhibit hormone-induced inositol phosphate formation. Cytosolic alkalinization also suppressed Ca2+ oscillations. However, prevention of intracellular acidosis with monensin (10 microM) did not prevent suppression of Ca2+ oscillations during chemical hypoxia. Mitochondrial depolarization with uncoupler did not change free Ca2+ levels during chemical hypoxia, indicating that mitochondria do not regulate free Ca2+ during chemical hypoxia. From these results, we conclude: 1) chemical hypoxia does not block Na+ influx across the plasma membrane; 2) Chemical hypoxia inhibits hormone-stimulated Ca2+ flux pathways across cellular membranes by two different mechanisms: (a) by ATP depletion, which disrupts hormone-myo-inositol 1,4,5-triphosphate coupling, and (b) by intracellular acidosis, which inhibits myo-inositol 1,4,5-triphosphate-stimulated Ca2+ release from intracellular stores; 3) during ATP depletion by chemical hypoxia, mitochondria do not take up Ca2+ to maintain cytosolic free Ca2+ at low concentrations. PMID- 1939070 TI - Micellar subunit assembly in a three-layer model of oligomeric alpha-crystallin. AB - Differential scanning calorimetry was performed to monitor the heat-induced changes that occur in the structural domain of lens alpha-crystallin. Circular dichroism and fluorescence also were used to resolve the controversial issue of the quaternary structure of alpha-crystallin. Based on the thermal behavior as monitored by these techniques, a model is proposed that can account for all previous data as well as the currently reported thermal data. The proposed model of native alpha-crystallin has a three-layer structure in which the inner layer (core) is a micelle containing 12 subunits arranged in cuboctahedral symmetry. The apolar region is directed inward constituting a hydrophobic core similar to a micelle and adding structural stability. A second layer of six subunits has a similar but not identical structure to the first layer, directing its apolar face toward the hydrophobic core. Thus, these two layers constitute a micelle-like structure with octahedral symmetry. The third layer adds more subunits for a total of not more than 24. Differential scanning calorimetry, circular dichroism, and fluorescence studies indicated that the inner two-layer structure of molecular mass 360 kDa is highly stable and is most likely of the alpha m form. The three-layer structure of the native protein, however, is rather unstable. At 35-45 degrees C the outer layer dissociates from the inner two layers, and at higher temperatures rapidly reassociates to a slightly modified two-layer structure with a stability similar to that of alpha m. The proposed model does not require any specific assembly of the alpha A and alpha B subunits in each layer, but the fluorescence results suggest that the native inner two layers probably contain mostly alpha A. PMID- 1939071 TI - Crystallographic analysis at 3.0-A resolution of the binding to human thrombin of four active site-directed inhibitors. AB - The mode of binding of four active-site directed inhibitors to human thrombin has been determined by x-ray crystallographic analysis. The inhibitors studied are benzamidine, PPACK, NAPAP, and MD-805, of which the last three are compounds evolved specifically to inhibit thrombin. Crystal structures were determined in the presence of both the inhibitor and the undecapeptide [des-amino Asp55]hirudin(55-65) which binds distant from the active site. Despite having significantly different chemical structures, NAPAP and MD-805 bind to thrombin in a very similar "inhibitor binding mode" which is not that expected by direct analogy with the binding of substrate. Both inhibitors bind to thrombin in a similar way as to trypsin, but thrombin has an extra loop, the "Tyr-Pro-Pro-Trp loop," not present in trypsin, which gives further binding interactions and is seen to move somewhat to accommodate binding of the different inhibitors. The fact that NAPAP and MD-805 require different stereochemistry for potent inhibition is demonstrated, and its structural basis clarified. The wealth of data on analogs and variants of these lead compounds is shown to be compatible with this inhibitor binding mode. PMID- 1939072 TI - Depalmitylation with hydroxylamine alters the functional properties of rhodopsin. AB - Rhodopsin, the photosensitive protein found in rod photoreceptors, has two covalently attached palmitates that are thought to anchor a portion of the C terminus to the disc membrane, forming a fourth cytoplasmic loop. Using hydroxylamine (NH2OH) to cleave the thioester linkage, we have characterized the effect of depalmitylation on certain functional properties of rhodopsin. Treatment of rod outer segment membranes (prepared from rat retinas previously labeled in vivo with [3H]palmitate) with 1 M NH2OH typically removed greater than or equal to 75% of the [3H]palmitate initially bound to rhodopsin. Spectrophotometry of rod outer segment membranes that had been treated with 1 M NH2OH indicated preservation of 85% of the native rhodopsin and no effect on the shape of the absorbance spectrum of rhodopsin. In vivo labeled rhodopsin that had been treated with 1 M NH2OH did not reincorporate free endogenous [3H] palmitate over a 2-h incubation period. Both NH2OH-treated and untreated rhodopsin incorporated [14C]palmitate from exogenously added [14C]palmitoyl-CoA. This incorporation was substantially greater in the NH2OH-treated sample. The removal of palmitate by NH2OH inhibited rhodopsin regeneration by 44% and increased the ability of rhodopsin to activate transducin's light-dependent GTPase activity by 61%. However, the removal of palmitate from rhodopsin did not affect the light dependent binding of transducin (T alpha and T beta gamma). PMID- 1939073 TI - Functional mapping of anthrax toxin lethal factor by in-frame insertion mutagenesis. AB - Linker insertion mutagenesis was employed to create structural disruptions of the lethal factor (LF) protein of anthrax toxin to map functional domains. A dodecameric linker was inserted at 17 blunt end restriction enzyme sites throughout the gene. Paired MluI restriction sites within the linker allowed the inserts to be reduced from four to two amino acids. Shuttle vectors containing the mutated genes were transformed into the avirulent Bacillus anthracis UM23C1-1 for expression and secretion of the gene products. Mutations at five sites in the central one-third of the sequence made the protein unstable, and purified protein could not be obtained. Mutated LF proteins with insertions at the other sites were purified and assessed for toxic activity in a macrophage lysis assay and for their ability to bind to the protective antigen (PA) component of anthrax toxin, the receptor binding moiety. Most insertions located in the NH2-terminal one third of the LF protein eliminated both toxicity and binding to PA, while all four insertions in the COOH-terminal one-third of the protein eliminated toxicity without affecting binding to PA. These data support the hypothesis that the NH2 terminal domain contains the structures required for binding to PA and the COOH terminal domain contains the putative catalytic domain of LF. PMID- 1939074 TI - Systematic use of the incomplete factorial approach in the design of protein crystallization experiments. AB - We have used the Incomplete Factorial Approach (Carter, C. W., and Carter, C. W., Jr. (1979) J. Biol. Chem. 254, 12219-12223) in conjunction with the program Cristal (Roussel, A., Serre, L., Frey M., and Fontecilla-Camps, J. (1990) J. Crystal Growth 106, 405-409) to crystallize six different proteins. We were able to obtain crystals and to identify the critical factors for crystallization for each of these six proteins. In some of the cases, we succeeded on the first try while using only minute amounts of protein. This study proves that the Incomplete Factorial Approach is a powerful tool in identifying the factors that need to be varied to achieve crystallization. Single crystals of adequate size were obtained for all the proteins reported here, although some did not diffract well enough to be studied by x-ray diffraction methods; the asymmetric units of these latter crystals contain a large metric units of these latter crystals contain a large number of molecules, which is most likely due to the presence of significant amounts of carbohydrate in the proteins. PMID- 1939075 TI - Activated protein C-catalyzed inactivation of human factor VIII and factor VIIIa. Identification of cleavage sites and correlation of proteolysis with cofactor activity. AB - Human factor VIII and factor VIIIa were proteolytically inactivated by activated protein C. Cleavages occurred within the heavy chain (contiguous A1-A2-B domains) of factor VIII and in the heavy chain-derived A1 and A2 subunits of factor VIIIa, whereas no proteolysis was observed in the light chain or light chain-derived A3 C1-C2 subunit. Reactivity to an anti-A2 domain monoclonal antibody and NH2 terminal sequence analysis of three terminal digest fragments from factor VIII allowed ordering of fragments and identification of cleavage sites. Fragment A1 was derived from the NH2 terminus and resulted from cleavage at Arg336-Met337. The A2 domain was bisected following cleavage at Arg562-Gly563 and yielded fragments designated A2N and A2C. A third cleavage site is proposed at the A2-B junction (Arg740-Ser741) since fragment A2C was of equivalent size when derived either from factor VIII or factor VIIIa. The site at Arg562 was preferentially cleaved first in factor VIII(alpha) compared with the site at Arg336, and it was this initial cleavage that most closely correlated with the loss of cofactor activity. Factor VIIIa was inactivated 5-fold faster than factor VIII, possibly as a result of increased protease utilization of the site at Arg562 when the A2 subunit is not contiguous with the A1 domain. When initial cleavage occurred at Arg336, it appeared to preclude subsequent cleavage at Arg562, possibly by promoting dissociation of the A2 domain (subunit) from the A1/light chain dimer. This conclusion was supported by the failure of protease treated A1/A3-C1-C2 dimer to bind A2 subunit and gel filtration analysis that showed dissociation of the A2 domain-derived fragments, A2N and A2C, from the A1 fragment/light chain dimer. These results suggest a mechanism for activated protein C-catalyzed inactivation of factor VIII(alpha) involving both covalent alteration and fragment dissociation. PMID- 1939076 TI - Molecular cloning and targeted mutagenesis of the gene psaF encoding subunit III of photosystem I from the cyanobacterium Synechocystis sp. PCC 6803. AB - Photosystem I is one of the two multisubunit pigment-protein complexes in the thylakoid membranes of cyanobacteria. Subunit III of photosystem I complex was isolated from a mutant of the cyanonbacterium Synechocystis sp PCC 6803, which lacks subunit II. The sequence of its NH2-terminal residues was determined and corresponding oligonucleotide probes were used to isolate the gene encoding this subunit. The gene, designated as psaF, codes for a mature protein of 15705 Da that is synthesized with a 23-amino acid extension. The deduced amino acid sequence is homologous to subunit III from spinach and Chlamydomonas reinhardtii. The presequence of subunit III shows characteristics typical of bacterial presequences and exhibits remarkable amino acid identity around the proteolytic processing site when compared to corresponding regions from the precursors of eukaryotic subunit III. There are two conserved hydrophobic regions in the mature subunit III which may cross or interact with thylakoid membrane. The gene psaF exists as a single copy in the genome and is expressed as a monocistronic RNA. A stable mutant strain in which the gene psaF was replaced by a gene conferring resistance to kanamycin was generated by targeted mutagenesis. Photoautotrophic growth of the mutant strain was comparable with that of the wild type suggesting that function of subunit III is dispensable for photosynthesis in Synechocystis sp. PCC 6803. Addition of more MgSO4 to BG11 medium enhanced growth of the mutant strain but not of the wild type cells. PMID- 1939078 TI - Covalent modification of guanine bases in double-stranded DNA. The 1.2-A Z-DNA structure of d(CGCGCG) in the presence of CuCl2. AB - We have solved the single crystal structure to 1.2-A resolution of the Z-DNA sequence d(CGCGCG) soaked with copper(II) chloride. This structure allows us to elucidate the structural properties of copper in a model that mimics a physiologically relevant environment. A copper(II) cation was observed to form a covalent coordinate bond to N-7 of each guanine base along the hexamer duplex. The occurrence of copper bound at each site was dependent on the exposure of the bases and the packing of the hexamers in the crystal. The copper at the highest occupied site was observed to form a regular octahedral complex, with four water ligands in the equatorial plane and a fifth water along with N-7 of the purine base at the axial positions. All other copper complexes appear to be variations of this structure. By using the octahedral complex as the prototype for copper(II) binding to guanine bases in the Z-DNA crystal, model structures were built showing that duplex B-DNA can accommodate octahedral copper(II) complexes at the guanine bases as well as copper complexes bridged at adjacent guanine residues by a reactive dioxygen species. The increased susceptibility to oxidative DNA cleavage induced by copper(II) ions in solution of the bases located 5' to one or more adjacent guanine residues can thus be explained in terms of the cation and DNA structures described by these models. PMID- 1939077 TI - Intracellular Ca2+ pools in PC12 cells. Three intracellular pools are distinguished by their turnover and mechanisms of Ca2+ accumulation, storage, and release. AB - Three, non-cytosolic Ca2+ pools were characterized in intact PC12 cells. The first pool, sensitive to both inositol 1,4,5-trisphosphate and caffeine (Zacchetti, D., Clementi, E., Fasolato, C., Zottini, M., Grohovaz, F., Fumagalli, G., Pozzan, T., and Meldolesi, J. (1991) J. Biol. Chem. 266, 20152-20158) accounts for approximately equal to 200 microM of Ca2+/liter of cell water (less than 30% of total exchangeable Ca2+) and takes up Ca2+ from the cytosol via a Ca(2+)-ATPase, blocked by thapsigargin. A second pool, approximately equal to 400 microM/liter, is insensitive to both inositol 1,4,5-trisphosphate, caffeine, and thapsigargin and is released by the Ca2+ ionophore ionomycin. This pool is probably heterogeneous and its intracellular localization and physiological roles remain undefined. The third pool, approximately equal to 170 mumoles of Ca2+/liter, was discharged by the combination of ionomycin together with a substance that collapsed intracellular pH gradients, such as monensin or NH4Cl. This indicates that the pool is acidic, at variance with the first two. When exocytosis was stimulated, the size of this pool declined, indicating its primary residence within secretory granules. In the conditions of our experiments no major transfer of Ca2+ among the pools seemed to occur. This is the first comprehensive description of non-cytosolic Ca2+ pools investigated in intact neurosecretory cells by non-invasive procedures. PMID- 1939079 TI - Base-specific binding of copper(II) to Z-DNA. The 1.3-A single crystal structure of d(m5CGUAm5CG) in the presence of CuCl2. AB - The single crystal structure of d(m5CGUAm5CG) soaked with copper(II) chloride was solved to atomic (1.3 A) resolution to study the base specificity of copper binding to double-stranded DNA. In the present copper(II) chloride-soaked structure, four crystallographically unique copper(II) complexes were observed bound to five of the six purine bases in the hexamer duplex. Covalent copper(II) binding occurred at N-7 of all four guanine bases and at one of the two adenine bases in the DNA duplex. Copper binding was not observed at the position (Ade4) located in an open solvent channel, whereas the second adenine site (Ade10) shared a complex with a guanine residue (Gua12) of a neighboring symmetry-related hexamer. The coordination geometries and distribution of these copper(II) complexes at the guanine bases in the crystal were comparable to the analogous sites in the isomorphous copper(II) chloride-soaked d(CGCGCG) crystal (Kagawa, T., Geierstanger, B. H., Wang, A. H.-J., and Ho, P.S. (1991) J. Biol. Chem. 266, 20175-20184). Thus, the decreased copper(II) binding affinity for Ade4 was not an artifact of crystal packing, but is intrinsic to the chemical properties of this purine base in duplex DNA. This suggests that the adenine bases in dilute solutions of Z-DNA and more generally other duplex DNA conformations are not susceptible to copper(II) modification. Thus, preferential copper(II) binding at guanine bases over adenine bases in double-stranded DNA may explain the observed specificity of copper(II)-induced oxidative DNA damage near guanine residues (Yamamoto, K., and Kawanishi, S. (1989) J. Biol. Chem. 264, 15435-15440; Sagripanti, J.-L., and Kraemer, K. H. (1989) J. Biol. Chem. 264, 1729-1734). The sharing of a single copper(II) complex by Ade10 and Gua12 of an adjacent hexamer suggests that additional and perhaps specific DNA-DNA interactions, as may be found in the densely packed environment of the nuclear matrix in the cell, may render N-7 of adenine bases prone to copper(II) modification. PMID- 1939080 TI - Thyroglobulin processing by thyroidal proteases. Major sites of cleavage by cathepsins B, D, and L. AB - The normal provision of thyroid hormones to the body requires their release from the prohormone, thyroglobulin (Tg). Previous work established the importance of cathepsins B, D, and L (formerly designated cysteine proteinase I) to this process but had not defined the points of proteolytic attack for each enzyme. In the present study we labeled rabbit Tg in vivo with sodium 125I and performed limited digestions with cathepsins B, D, and L, purified from human thyroids. The resultant peptide fragments were analyzed by amino-terminal sequencing and located within the Tg molecule by comparison with the cDNA-derived sequences from human Tg. We identified three cleavage points for cathepsin B, corresponding to P'1 residues 532, 795, and 2487; four cleavage points for cathepsin L, corresponding to P'1 residues 2389, 2452, 2490, and 2657; and four cleavage points for cathepsin D, corresponding to P'1 residues 551, 1835, 2468, and 2643. None of the cleavage points was near Tgs known hormonogenic sites, but these peptide fragments contained three of the four major hormonogenic sites in rabbit Tg, suggesting some preference for their early proteolytic processing. Cathespin B alone among the three endopeptidases had some exopeptidase activity toward Tg. The cleavage specificities for each of the endopeptidases resembled those described with other protein substrates. Thus, cathepsin D preferentially cleaved bonds between hydrophobic residues, and cathespin L cleaved bonds with hydrophobic residues at P2 and P3. Although cathepsin Bs specificity was less obvious, it produced a major cleavage between 2 leucine residues. The existence of three endopeptidases cleaving at different sites shows that Tg proteolysis is a complex process, suggests synergism among their enzyme activities, and provides a physiological mechanism for selective hormone release, including its regulation by TSH. PMID- 1939081 TI - Enzymatic properties of mutant Escherichia coli tryptophan synthase alpha subunits. AB - Thirty-nine mutant tryptophan synthase alpha subunits have been purified and analyzed (in the presence of the beta 2-subunit) for their enzymatic (kcat, Km) behavior in the reactions catalyzed by the alpha 2.beta 2 complex, the fully constituted form of this enzyme. The mutant alpha subunits, obtained by in vitro random, saturation mutagenesis of the encoding trpA gene, contain single amino acid substitutions at sites within the first 121 residues of the alpha polypeptide. Four categories of altered residues have been tentatively assigned roles in the catalytic functions of this enzyme: 1) catalytic residues (Glu49 and Asp60); 2) residues involved in substrate binding or orientation (Phe22, Thr63, Gln65, Tyr102, and Leu105); 3) residues involved in alpha.beta subunit interactions (Gly51, Pro53, Asp56, Asp60, Pro62, Ala67, Phe72, Thr77, Pro78, Tyr102, Asn104, Leu105, and Asn108); and 4) residues with no apparent catalytic roles. Catalytic residue alterations result in no detectable activity in the alpha-subunit specific reactions. Substrate binding/orientation roles are detected enzymatically primarily as rate defects; alterations only at Tyr102 result in apparent Km effects. alpha.beta interaction roles are detected as rate defects in all tryptophan synthase reactions plus Km increases for the alpha subunit substrate, indole-3-glycerol phosphate, only when L-serine is present at the beta 2-subunit active site. A substitution at only one site, Asn104, appears to be unique in its potential effect on intersubunit channeling of indole, the product of the alpha-subunit specific reaction, to the beta 2-subunit active site. PMID- 1939082 TI - Evidence that functional erythrocyte-type glucose transporters are oligomers. AB - In this study we tested the hypothesis that functional erythrocyte-type glucose transporters (GLUT1) exist as oligomeric complexes by expressing chimeric transporter proteins in Chinese hamster ovary cells harboring endogenous GLUT1 transporters. The chimeric transporters were GLUT1-4c, in which the 29 C-terminal residues of human GLUT1 were replaced by the 30 C-terminal residues of rat skeletal muscle glucose transporter (GLUT4), and GLUT1n-4, containing the N terminal 199 residues of GLUT1 and the 294 C-terminal residues of GLUT4. Endogenous GLUT1 was quantitatively co-immunoprecipitated by using an anti-GLUT4 C-terminal peptide antibody from detergent extracts of Chinese hamster ovary cells expressing either of the chimeric proteins, as detected by immunoblotting the precipitates with an anti-GLUT1 C-terminal peptide antiserum. No co immunoprecipitation of native GLUT1 with native GLUT4 from extracts of 3T3-L1 adipocytes, which contain both these transporters, was observed with the same antibody. These data are consistent with the hypothesis that GLUT1 transporters exist as homodimers or higher order oligomers and that a major determinant of oligomerization is located within the first 199 residues of GLUT1. PMID- 1939083 TI - The N-terminal acidic domain of heparin cofactor II mediates the inhibition of alpha-thrombin in the presence of glycosaminoglycans. AB - Heparin cofactor II (HCII) is a glycoprotein in human plasma that inhibits thrombin and chymotrypsin. Inhibition occurs when the protease attacks the reactive site peptide bond in HCII (Leu444-Ser445) and becomes trapped as a covalent 1:1 complex. Dermatan sulfate and heparin increase the rate of inhibition of thrombin, but not of chymotrypsin, greater than 1000-fold. The N terminal portion of HCII contains two acidic repeats (Glu56-Asp-Asp-Asp-Tyr-Leu Asp and Glu69-Asp-Asp-Asp-Tyr-Ile-Asp) that may bind to anion-binding exosite I of thrombin to facilitate covalent complex formation. To examine the importance of the acidic domain, we have constructed a series of 5' deletions in the HCII cDNA and expressed the recombinant HCII (rHCII) in Escherichia coli. Apparent second-order rate constants (k2) for inhibition of alpha-thrombin and chymotrypsin by each variant were determined. Deletion of amino acid residues 1 74 had no effect on the rate of inhibition of alpha-thrombin or chymotrypsin in the absence of a glycosaminoglycan. Similarly, the rate of inhibition of alpha thrombin in the presence of a glycosaminoglycan was unaffected by deletion of residues 1-52. However, deletion of residues 1-67 (first acidic repeat) or 1-74 (first and second acidic repeats) greatly decreased the rate of inhibition of alpha-thrombin in the presence of heparin, dermatan sulfate, or a dermatan sulfate hexasaccharide that comprises the minimum high-affinity binding site for HCII. Deletion of one or both of the acidic repeats increased the apparent affinity of rHCII for heparin-Sepharose, suggesting that the acidic domain may interact with the glycosaminoglycan-binding site of native rHCII. The stimulatory effect of glycosaminoglycans on native rHCII was decreased by a C-terminal hirudin peptide which binds to anion-binding exosite I of alpha-thrombin. Furthermore, the ability of native rHCII to inhibit gamma-thrombin, which lacks the binding site for hirudin, was stimulated weakly by glycosaminoglycans. These results support a model in which the stimulatory effect of glycosaminoglycans on the inhibition of alpha-thrombin is mediated, in part, by the N-terminal acidic domain of HCII. PMID- 1939084 TI - Phorbol ester-stimulated hydrolysis of phosphatidylcholine and phosphatidylethanolamine by phospholipase D in HeLa cells. Evidence that the basal turnover of phosphoglycerides does not involve phospholipase D. AB - 12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulated the release of [3H]ethanolamine from HeLa cells prelabeled with [3H]ethanolamine within 2 min, and of [3H]choline from cells prelabeled with [3H]choline after a lag of 10-20 min. This result suggests that TPA activates phospholipase D. Propranolol alone or propranolol plus TPA stimulated phosphatidic acid (PA) labeling in cells prelabeled with [3H]hexadecanol. In the presence of ethanol, TPA stimulated the accumulation of labeled phosphatidylethanol (PEth); no PEth was formed in the absence of TPA. TPA-dependent PEth accumulation was not observed in cells pretreated with TPA to down-regulate protein kinase C, whereas propranolol induced accumulation of PA was unaffected by TPA pretreatment. Incubation of prelabeled cells with propranolol alone caused a rapid loss of label and phospholipid mass from both phosphatidylethanolamine and phosphatidylcholine (PC) together with an accumulation of PA and phosphatidylinositol plus phosphatidylserine. When [3H]hexadecanol-prelabeled cells were pulse labeled with 32P to label nucleotide pools, propranolol induced the accumulation of both 3H- and 32P-labeled PA. When cells were prelabeled with lyso-PC double labeled with 3H and 32P, and incubated with propranolol, only 3H-labeled PA accumulated, indicating that the pathways involved in the basal turnover of PC resulted in the loss of 32P from the lipid. These results suggest that the basal turnover of phosphatidylethanolamine and PC involves the sequential actions of phospholipase C, diglyceride kinase, and PA phosphohydrolase. PMID- 1939085 TI - Structural characterization of the asparagine-linked oligosaccharides from Trypanosoma brucei type II and type III variant surface glycoproteins. AB - The complete primary structures of the major Asn-linked oligosaccharides from the type II variant surface glycoproteins (VSGs), MITat 1.2 and MITat 1.7, and the type III VSG, MITat 1.5, were determined using a combination of exo- and endoglycosidase digestions, methylation analysis, acetolysis, and 500 MHz 1H NMR spectroscopy. Each variant contained classical branched oligomannose-type and biantennary complex oligosaccharides, a proportion of the latter substituted with terminal alpha(1-3)-linked galactose residues, the first report of the presence of this epitope in Trypanosoma brucei. In addition both the type II variants contained relatively large amounts of the unusual small oligomannose-type oligosaccharides, Man4GlcNAc2 and Man3GlcNAc2, and a diverse array of novel branched poly-N-acetyllactosamine oligosaccharides, similar but not identical to those from mammalian glycoproteins. These latter structures were also partially substituted with terminal alpha(1-3)-linked galactose residues. Glycosylation in the type II variants showed site specificity in that the poly-N-acetyllactosamine and Man(9-5)GlcNAc2 oligosaccharides were located exclusively at Asn glycosylation site 1 very close to the C terminus, whereas the Man(4-3)GlcNAc2 and biantennary complex oligosaccharides were located exclusively at site 2. This is the first report of the presence of poly-N-acetyllactosamine oligosaccharides in protozoa. PMID- 1939087 TI - Mitochondrial creatine kinase mediates contact formation between mitochondrial membranes. AB - Purified mitochondrial creatine kinase (Mi-CK) (EC 2.7.3.2) from chicken heart was shown to interact simultaneously with purified inner and outer mitochondrial membranes, thereby creating an intermembrane chondrial membranes, thereby creating an intermembrane were purified from rat liver and thus were fully devoid of Mi-CK. Intermembrane contact formation was demonstrated by measuring the binding of inner membrane vesicles to outer membranes spread at the air-water interface. Mi-CK also mediated intermembrane adhesion when membranes formed with total lipid extracts of both membranes were used, pointing to the role of lipids as potential membrane anchors of Mi-CK in the mitochondrial intermembrane space. Other enzymes of the intermembrane space that (like Mi-CK) are also cationic, as well as cytosolic isoenzymes of creatine kinase, failed to induce contact formation. Thus, of the proteins tested, membrane contact formation was specific for Mi-CK. The two oligomeric forms of Mi-CK (octamer and dimer) differed in their ability to mediate intermembrane adhesion, the octamer being more potent. Highly basic peptides, i.e. poly-L-lysines, were shown to strongly interact with membranes formed with lipid extracts of mitochondrial membranes: they both induced intermembrane binding and fusion. Interestingly, the extent of contact formation mediated by poly-L-lysines was lower than that of octameric Mi-CK. The implications of these findings on the function and localization of Mi-CK and on the structure of the mitochondrial intermembrane compartment are discussed. PMID- 1939086 TI - Expression of a G protein subunit, alpha i-1, in Balb/c 3T3 cells leads to agonist-specific changes in growth regulation. AB - Cellular receptors for many hormones, neurotransmitters, and growth factors are coupled to intracellular effector enzymes or ion channels through a set of heterotrimeric G proteins. In order to determine whether isoforms of G protein alpha subunits contribute differentially to mitogenic responses, we introduced an alpha subunit isoform, alpha i-1, into Balb/c 3T3 cells that normally lack this subtype. Balb/c 3T3 cells transfected with a plasmid containing cDNA encoding alpha i-1 expressed the alpha i-1 protein as judged both by the appearance of immunoreactive alpha i-1 protein on Western blots and by two-dimensional analysis of the proteins [32P]ADP-ribosylated by pertussis toxin. The amount of alpha i-1 expressed is less than the amount of alpha subunits endogenously present in these cells. Expression of alpha i-1 in the transfected cells slightly blunts stimulation of adenylylcyclase by GTP, guanosine 5'-3-O-(thio)triphosphate, or forskolin, but has no major effect on the ability of thrombin to inhibit the enzyme. In contrast, the expression of alpha i-1 has significant effects on cell growth and on the mitogenic response to thrombin. The alpha i-1-transfected cells have a doubling time that is twice as long as control cells transfected with the same plasmid without a cDNA insert. Despite their slower growth, thymidine incorporation in response to thrombin is greater in transfected than in control cells. Thrombin-stimulated DNA synthesis is sensitive to inhibition by pertussis toxin and is 5-fold more sensitive to inhibition by pertussis toxin in transfected cells than in control cells. The changes are receptor-specific since the mitogenic response to platelet-derived growth factor is indistinguishable between control and transfected cells. These studies suggest that the alpha i subunit composition of the cell may have profound effects on its growth and its response to stimulation through a specific cell surface receptor. PMID- 1939088 TI - Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding. AB - To further evaluate the bioenergetic role of phosphocreatine, we assessed several parameters in normal and depleted rat hearts. Rats were fed (8 weeks) a diet containing either 1% beta-guanidinoproprionic acid or 2% beta-guanidinobutyric acid (beta-GBA), resulting in an 80% phosphocreatine depletion compared to controls. Left ventricular pressure-volume curves were obtained to determine contractile function. At any volume, the developed pressure in depleted hearts was lower than in controls. At the plateau, the rate-pressure product was between 37-45% lower: 34,000 (beta-GBA), 30,174 (beta-guanidinoproprionic acid) versus 54,400 (control). 31P NMR spectroscopy on beta-GBA-treated hearts obtained the [ATP] and [phosphocreatine], which with saturation transfer estimated the rates of creatine kinase and ATP production. In depleted hearts, the rate constant for ATP synthesis from phosphocreatine was increased 33%. However, the flux was 72% lower. ATP production from ADP and Pi were similar under normal conditions, in spite of higher rates of oxygen consumption in the depleted hearts. The addition of 50 mM creatine to control perfusate had no effect on function or high energy phosphates. In contrast, a 28% increase in function and a 52% increase in [phosphocreatine] was seen in beta-GBA hearts. There was a marked increase in free [ADP] in beta-GBA hearts, resulting in a lower estimated ATP phosphorylation potential. Overall, the results suggest that phosphocreatine may play an important function by optimizing the thermodynamics of cardiac high energy phosphate utilization. PMID- 1939089 TI - Molecular cloning of the mouse mast cell protease-5 gene. A novel secretory granule protease expressed early in the differentiation of serosal mast cells. AB - cDNAs were isolated that encode mouse mast cell protease-5 (MMCP-5), an approximately 30,000 Mr serine protease stored in the secretory granules of serosal mast cells (SMC) and Kirsten sarcoma virus-immortalized mast cells. Based on the deduced amino acid sequences of these cDNAs, MMCP-5 is synthesized as a 247-amino acid preproenzyme composed of a novel 19-residue hydrophobic signal peptide, a Gly-Glu activation peptide not present in other mast cell chymases, and a 226-amino acid protein that represents the mature enzyme. MMCP-5 possesses a unique Asn residue in the substrate binding cleft at residue 176 and is highly basically charged. The MMCP-5 gene was isolated, sequenced, and found to belong to a distinct subset of chymase genes. Allelic variations of the MMCP-5 gene were also detected. MMCP-5 is expressed in bone marrow-derived mast cells (BMMC), Kirsten sarcoma virus-immortalized mast cells, and SMC, but not in gastrointestinal mucosal mast cells of helminth-infected mice. The abundant levels of MMCP-5 mRNA in immature BMMC indicate that this chymase is expressed relatively early during the differentiation of mast cells. MMCP-5 is the first chymase to be molecularly cloned from progenitor mast cells and is also the first chymase shown to be expressed preferentially in the SMC subclass. PMID- 1939090 TI - Phagocytic cell molecules that bind the collagen-like region of C1q. Involvement in the C1q-mediated enhancement of phagocytosis. AB - C1q binds to and elicits cellular responses by several cell types, including monocytes, macrophages, neutrophils, B cells, and fibroblasts. The cell-binding domain is located within the collagen-like pepsin-resistant region of the C1q molecule (C1q tails). An affinity matrix of C1q tails coupled to Sepharose was used to select C1q-binding proteins from detergent extracts of surface-iodinated human monocytes, polymorphonuclear leukocytes, and the U937 cells. The major radiolabeled polypeptide eluted specifically from the ligand affinity column had an apparent molecular mass (Mr) of 126,000. Minor iodinated components eluted from Sepharose-tails migrated with Mr of 216,000 and 55,000. When subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions no change in the migration of any of these polypeptide bands was detected. None of these polypeptides reacted with antibodies directed against the integrins alpha 5 beta 1 (fibronectin receptor) or alpha v beta 3 (vitronectin receptor), LFA-1, or to several other cell adhesion molecules. The Mr 126,000 band was found to contain more than one polypeptide. Lectin binding properties, susceptibility to glycosidases and proteases, and immunoreactivity with the monoclonal antibody L-10, indicated that CD43 (sialophorin/leukosialin) is a component of this band. However, further data show that a monoclonal antibody, generated by immunization with the isolated Clq-binding fractions, recognizes a cell surface sialoglycoprotein distinct from CD43 and inhibits the C1q-mediated enhancement of phagocytosis in monocytes. These latter observations provide the first definitive connection between a specific phagocytic cell surface protein and a known C1q-mediated function. While these proteins contain sialic acid, binding assays and functional assays using neuraminidase-treated cells demonstrate that the functional interaction between C1q and the cell surface is not via sialic acid. The data taken together indicate either that the functional C1q receptor on phagocytic cells is a multi-subunit complex or that multiple proteins can interact with the fragment of C1q containing the cell-binding domain, at least one of which is involved in the C1q-mediated enhancement of phagocytosis. PMID- 1939091 TI - Alteration of N-terminal residues of mature human lysozyme affects its secretion in yeast and translocation into canine microsomal vesicles. AB - Signal sequences play a central role in the initial membrane translocation of secretory proteins. Their functions depend on factors such as hydrophobicity and conformation of the signal sequences themselves. However, some characteristics of mature proteins, especially those of the N-terminal region, might also affect the function of the signal sequences. To examine this possibility, several mutants of human lysozyme modified in the N-terminal region of the mature protein were constructed, and their secretion in yeast as well as in vitro translocation into canine pancreatic microsomes were analyzed using an idealized signal sequence L8 (MR(L)8PLAALG). Our results show the following. (1) Change in the charge at the N terminal residue of the mature protein does not affect secretion drastically. (2) Substitution of a proline residue at the N terminus prevents cleavage of the signal sequence, although translocation itself is not impaired. (3) Excessive positive charges in the N-terminal region delay translocation of the precursor protein across the membrane. (4) Polar and negatively charged residues introduced into the N-terminal region affect the secretion of the mature protein by preventing its correct folding. PMID- 1939092 TI - Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts. AB - We have investigated the nature of immediate cell signals produced by occupancy of the chicken osteoclast alpha v beta 3 integrin. Synthetic osteopontin and peptides from the osteopontin and bone sialoprotein sequences containing Arg-Gly Asp stimulated immediate reductions in osteoclast cytosolic Ca2+. The changes in cytosolic Ca2+ required the Arg-Gly-Asp sequence and were blocked by a monoclonal antibody to the alpha v beta 3 integrin, LM609. Osteoclast stimulation by the proteins through the integrin did not require immobilization since soluble peptides produced changes in cytosolic Ca2+ and inhibited osteoclast binding to bone particles and bone resorption. The decrease in cytosolic Ca2+ stimulated by osteopontin and related peptides appeared to be due to activation of a plasma membrane Ca(2+)-ATPase by calmodulin. Thus, the data suggest that ligand binding to the osteoclast alpha v beta 3 integrin results in calmodulin-dependent reduction in cytosolic Ca2+ which participates in regulation of osteoclast function. PMID- 1939093 TI - The length of the aminoacyl-acceptor stem of the selenocysteine-specific tRNA(Sec) of Escherichia coli is the determinant for binding to elongation factors SELB or Tu. AB - Mutations in selC, which reduce the 8-base pair aminoacyl-acceptor helix to the canonical 7-base pair length (tRNA(Sec)(delAc] or which replace the extra arm of tRNA(Sec) by that of a serine acceptor tRNA species (tRNA(Sec)(ExS), block the function in selenoprotein synthesis in vivo (Baron, C., Heider, J., and Bock, A. (1990) Nucleic Acids Res. 18, 6761-6766). tRNA(Sec), tRNA(Sec)(delAc), and tRNA(Sec)(ExS) were purified and analyzed for their interaction with purified seryl-tRNA synthetase, selenocysteine synthase and translation factors SELB and EF-Tu. It was found that seryl-tRNA synthetase displays 10-fold impaired Km and Kcat values for tRNA(Sec) in comparison to tRNA(Ser), decreasing the overall charging efficiency (Kcat/Km) of tRNA(Sec) to 1% of that characteristic for tRNA(Ser). tRNA(Sec)(ExS) was a less efficient substrate for the enzyme (Kcat/Km 0.2% of the tRNA(Ser) value) whereas the tRNA(Ser)(delAc) variant was charged with an approximately 2-3-fold improved rate compared to wild-type tRNA(Sec). Both mutant tRNA variants, when charged with L-serine, were able to interact with selenocysteine synthase to give rise to selenocysteyl-tRNA with tRNA(Sec)(ExS) being as efficient as wild-type tRNA(Sec). Seryl-tRNA(Sec)(delAc), on the other hand, was selenylated very slowly. Reduction of the length of the aminoacyl acceptor stem to 7 base pairs prevented the interaction with translation factor SELB but allowed binding to EF-Tu, irrespective of whether tRNA(Sec)(delAc) was charged with serine or selenocysteine. The aminoacyl-acceptor helix of tRNA(Sec), therefore, is a major determinant directing binding to SELB and precluding interaction with EF-Tu. PMID- 1939095 TI - Promoter activity and distance constraints of one versus two Sp1 binding sites. AB - In the simple adenovirus 2 early 1B (E1B) promoter, moving the single Sp1 transcription factor binding site (GC box) from its wild-type position eight base pairs (bp) from the TATA box to 30 bp upstream is equivalent to its deletion (Wu, L., and Berk, A. (1988) Genes & Dev. 2, 403-411). In more complex promoters, multiple upstream elements regulate transcription over greater distances. To understand these spacing constraints, we placed two GC boxes in phase at various distances from the E1B TATA box. Whereas one GC box at eight bp from TATA increases transcription in vivo 5-fold compared with TATA alone (Wu, L., Rosser, D. S. E., Schmidt, M. C., and Berk, A. (1987) Nature 326, 512-515), two GC boxes increased in vivo transcription 25-30-fold. Transcriptional stimulation by two GC boxes fell off rapidly in vivo at 30 bp from TATA, remained approximately constant through 50 bp, then decreased again at 70 bp. Consequently, two GC boxes have a multiplicative effect at eight bp from TATA and continue to stimulate transcription at a greater distance from TATA than a single Sp1 site. Quantitatively different results were observed for in vitro transcription using a nuclear extract; a more linear fall off with increasing distance from TATA was observed. Separating the two GC boxes progressively decreased transcription. E1A stimulation of these promoters in vivo indicates that Sp1 transcription control is independent of E1A transactivation. PMID- 1939096 TI - Nutritional regulation and tissue-specific expression of the serine dehydratase gene in rat. AB - The mechanism of dietary regulation and tissue-specific expression of the serine dehydratase gene in rat has been studied. The hepatic serine dehydratase activity and its mRNA showed a parallel increase with increasing protein content in the diet. However, when rats that had been maintained on a high protein diet were fed a protein-free diet, the mRNA level rapidly decreased to 0.5 in 3 h, whereas the enzyme activity gradually fell to a low level over a period of 5 days. With animals maintained on a high protein diet or on a protein-free diet, we examined the sites hypersensitive to DNase I in the 5'-flanking region of serine dehydratase gene in the liver chromatins. A series of DNase I-hypersensitive sites were located within 10.5 kilobase pairs upstream of the transcription start site. The DNA regions at -3050 and -3180 (region II) and -3600 to -3850 (region III) were more susceptible to the nuclease in the expressing than in the nonexpressing liver. A reverse situation obtained at -100 (region I). Kidney contained serine dehydratase mRNA at a level of 5% of liver as determined by Northern blotting. The kidney chromatin was found to be susceptible to DNase I only at region I. No conspicuous DNase I-hypersensitive sites were observed in the relevant regions of chromatins from brain and lung, in which serine dehydratase mRNA was scarcely transcribed. These results suggest that nutritional control and tissue-specific expression of the serine dehydratase gene is closely associated with the alteration of DNase I hypersensitivity at specific sites of the 5'-flanking region of the gene. PMID- 1939094 TI - Phosphorylation of the beta subunit of casein kinase II in human A431 cells. Identification of the autophosphorylation site and a site phosphorylated by p34cdc2. AB - To examine the phosphorylation of casein kinase II in cells, the enzyme was isolated by immunoprecipitation from metabolically labeled human epidermal carcinoma A431 cells using polyclonal antipeptide antibodies specific for either the alpha subunit or the beta subunit of the enzyme. When isolated from 32P labeled cells, the beta subunit was found to be significantly labeled on serine residues whereas only minimal labeling was associated with the alpha subunit. In vitro, the beta subunit of purified bovine casein kinase II was autophosphorylated, also on serine residues. Cleavage of the beta subunit, that had been autophosphorylated in vitro, at tryptophan 9 and tryptophan 12 using N chlorosuccinimide demonstrated that the autophosphorylation site is located near the amino terminus of the protein, most likely at serine 2 and serine 3. Two dimensional maps of phosphopeptides generated by digestion of the beta subunit with endoproteinase Glu-C indicted that the majority of the phosphate that was incorporated into the protein in cells was at sites that were indistinguishable from the sites that were autophosphorylated in vitro. In addition to phosphorylation at the autophosphorylation site, the beta subunit is also phosphorylated at an additional site, serine 209, in intact cells. This residue, which is near the carboxyl terminus of the protein, can be phosphorylated in vitro by p34cdc2. PMID- 1939097 TI - Cartilage matrix proteins. A basic 36-kDa protein with a restricted distribution to cartilage and bone. AB - A non-collagenous quantitatively prominent protein was purified from guanidine hydrochloride extracts of bovine tracheal cartilage. Purification was achieved by cesium chloride density gradient centrifugation and chromatography on DEAE cellulose at pH 7.0 followed by CM-cellulose at pH 5.0. The protein has a marked tendency to form aggregates in denaturing solutions of high ionic strength, e.g. 6 M guanidine hydrochloride. The purified protein contains a single, Mr 36,000 polypeptide chain, with a particularly high content of leucine. It contains about 1% carbohydrate with a remarkable absence of hexosamines and sialic acid, whereas xylose, galactose, mannose, and fucose were identified in the preparation. The protein was identified in extracts of cartilage and bone and could be shown to be primarily extracellular. Tendon may contain trace amounts of the protein, whereas extracts of several other tissues showed no immunoreactivity in enzyme-linked immunosorbent assay. PMID- 1939098 TI - Identification, expression, and deduced primary structure of transketolase and other enzymes encoded within the form II CO2 fixation operon of Rhodobacter sphaeroides. AB - Previous studies had indicated that the form II or B cluster of CO2 fixation structural genes is part of a large operon in Rhodobacter sphaeroides (Gibson, J. L., Chen, J.-H., Tower, P. A., and Tabita, F. R. (1990) Biochemistry 29, 8085 8093). In this investigation, we have sequenced the DNA between the prkB and rbpL genes and provide evidence for three distinct open reading frames which encode additional structural genes of the Calvin reductive pentose phosphate pathway; these genes encode the enzymes transketolase, glyceraldehyde phosphate dehydrogenase, and aldolase. Noteworthy is transketolase, which may be expressed to high levels in Escherichia coli. This study thus represents the initial description of the primary structure of bacterial transketolase, a key enzyme of the reductive and the oxidative pentose phosphate pathways. Each of the genes are separated by short stretches of intergenic sequence, consistent with earlier evidence which suggested that these genes are cotranscribed and part of a large operon controlled by sequences upstream from fbpB. PMID- 1939099 TI - Transcriptional activation of yeast nucleotide biosynthetic gene ADE4 by GCN4. AB - The yeast transcriptional regulator protein GCN4 harbors the bZIP DNA binding motif, which is common to a family of DNA-binding proteins in eukaryotic organisms from yeast to man. GCN4 and the mammalian activator protein AP-1 (jun/fos) regulate transcription by binding the same consensus DNA sequence ATGA (C/G)TCAT. GCN4 positively regulates the production of precursors of protein synthesis in yeast cells in response to the environmental signal "amino acid starvation." We find three GCN4 responsive elements (GCREs) in the 5'-flanking region of the purine biosynthetic gene ADE4 and demonstrate that GCN4 efficiently activates transcription of ADE4. Two GCREs are essential to synergistically activate ADE4 transcription by binding GCN4. The distal GCRE1 is also required for basal transcription of ADE4. Therefore, transcription factor GCN4 affects, in addition to protein biosynthesis, also nucleotide biosynthesis and, comparable to its mammalian counterpart AP-1, has a more general function within the yeast cell than previously assumed. PMID- 1939100 TI - Purification of diphtheria toxin receptor from Vero cells. AB - Diphtheria toxin receptor has been solubilized from Vero cell membranes with octyl beta-D-glucoside. CRM197, the product of a mutated diphtheria toxin gene, was used for the identification of the receptor. The binding activity of the solubilized receptor was assayed by precipitating the receptor with acetone in the presence of phospholipids and carrier proteins. The solubilized receptor was purified by the combination of several chromatographic steps in the presence of the detergent, resulting in about a 10(6)-fold purification of the receptor. The purified receptor showed essentially a single band of 14.5 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When partially purified receptor fractions were subjected to ligand blotting analysis using 125I-CRM197 as the probe, the 14.5-kDa protein and a few minor protein bands were identified as diphtheria toxin-binding molecules. These results show clearly that the 14.5-kDa protein is the diphtheria toxin receptor, or at least the major diphtheria toxin binding molecule. When partially purified receptor was applied to a Sephacryl S 300 column in the presence of detergent, the receptor was eluted in the fractions corresponding to the 60-90-kDa size range. This suggests that the protein forms a complex with itself or with another protein. PMID- 1939101 TI - An antibody that inhibits the binding of diphtheria toxin to cells revealed the association of a 27-kDa membrane protein with the diphtheria toxin receptor. AB - A monoclonal antibody that blocks the binding of diphtheria toxin to Vero cells was isolated by immunizing mice with Vero cell membrane. The antibody inhibits the binding of diphtheria toxin and also CRM197, a mutant form of diphtheria toxin, to Vero cells, and consequently inhibits the cytotoxicity of diphtheria toxin. This antibody does not directly react with the receptor molecule of diphtheria toxin (DTR14.5). Immunoprecipitation and immunoblotting studies revealed that this antibody binds to a novel membrane protein of 27 kDa (DRAP27). When diphtheria toxin receptor was passed through an affinity column made with this antibody, the receptor was trapped only in the presence of DRAP27. These results indicate that DRAP27 and DTR14.5 closely associate in Vero cell membrane and that the inhibition of the binding of diphtheria toxin to the receptor is due to the binding of the antibody to the DRAP27 molecule. Binding studies using 125I labeled antibody showed that there are many more molecules of DRAP27 on the cell surface than diphtheria toxin-binding sites. However, there is a correlation between the sensitivity of a cell line to diphtheria toxin and the number of DRAP27 molecules on the cell surface, suggesting that DRAP27 is involved in the entry of diphtheria toxin into the target cell. PMID- 1939102 TI - The COOH terminus of several liver carboxylesterases targets these enzymes to the lumen of the endoplasmic reticulum. AB - To investigate the potential role of the COOH-terminal peptides in retaining a family of soluble carboxylesterases in the lumen of the endoplasmic reticulum, the pI 6.1 esterase cDNA has been cloned into the pKCR3 vector for transient expression in COS cells. The plasmid-encoded product appeared to be identical to the authentic enzyme: it was active on alpha-naphthyl acetate and behaved as a homotrimer of noncovalently bound 60-kDa subunits which contain a single, endo beta-N-acetylglucosaminidase H-sensitive oligosaccharide chain. This enzyme was retained in the transgenic COS cells. In contrast, a mutated form ending in HVER COOH was secreted, indicating that the natural terminus HVEL-COOH contains topogenic information, with the ultimate Leu residue as an essential part. Variants of pI 6.1 esterase ending in HIEL-COOH, or HTEL-COOH were retained in cells to the same extent as the wild-type protein. Therefore, the sequences HIEL and HTEL present at the COOH termini of several liver esterases (rabbit forms 1 and 2, human esterase, mouse egasyn, and rat pI 6.4 esterase) most likely have a function in their localization in the endoplasmic reticulum. Finally, an HDEL COOH variant of pI 6.1 esterase was also normally retained, demonstrating that this signal can be correctly decoded by the sorting machinery of mammalian cells. Cell retention signals of the type HXEL-COOH appear to be common in higher eukaryotes and tolerate considerable variation at the antepenultimate X residue. PMID- 1939103 TI - Covalent linkage between nucleotides and platelet-derived endothelial cell growth factor. AB - Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa peptide mitogen which is present in platelets and placenta and produced by certain cultured cell lines. Immunoprecipitation of A431 cells metabolically labeled with [32P]orthophosphate revealed the incorporation of 32P radioactivity into PD-ECGF. Phosphoamino acid analysis showed that serine residues of PD-ECGF were phosphorylated in vivo. Forskolin, 12-O-tetradecanoylphorbol-13-acetate, and epidermal growth factor had no effect on the in vivo phosphorylation of PD-ECGF. Moreover, incubation of pure PD-ECGF with [gamma-32P]ATP led to labeling of PD ECGF. Optimal labeling was achieved by incubation at 95 degrees C for 5 min in the presence of sodium dodecyl sulfate, dithiothreitol, and Mg2+ or Mn2+. PD-ECGF was also labeled with [2,8-3H]ATP, [2,5',8-3H]ATP, or [alpha-32P]ATP. ATP and GTP were the preferred nucleotide substrates by comparison with other nucleotides and related components. Partial amino acid hydrolysis liberated a significant amount of O-[32P]phosphoserine from PD-ECGF labeled in vitro with [gamma-32P] ATP. Furthermore, 32P-radiolabeled nucleotides were released after snake venom phosphodiesterase or piperidine treatment from PD-ECGF labeled in vitro with [alpha-32P]ATP or [gamma-32P]ATP, as well as from PD-ECGF labeled in vivo with [32P]orthophosphate. These data indicate that serine residues of PD-ECGF can be covalently linked to phosphate groups of nucleotides, resulting in a nucleotidylated protein. The functional significance of this post-translational modification remains to be determined. PMID- 1939104 TI - Regulation of endoplasmic reticulum stress proteins in COS cells transfected with immunoglobulin mu heavy chain cDNA. AB - The mechanism by which endoplasmic reticulum (ER) stress proteins are induced by the accumulation of incompletely assembled or malfolded proteins in the ER is poorly understood. The 78-kDa glucose-regulated protein (BiP), one of the ER stress proteins, has often been detected in stable complexes with these accumulated proteins. We have transfected COS cells with an immunoglobulin (Ig) mu heavy chain expression plasmid. Expressed mu-chain accumulated in the cells and formed stable complexes with BiP. As a result, the synthesis of three ER stress proteins, BiP, the 94-kDa glucose-regulated protein (GRP94/ERp99), and ERp72, was increased as were their mRNA levels. In addition, the degradation rate of BiP was increased, possibly because of its interaction with mu-chain. Cotransfection of the mu-chain plasmid with an Ig lambda light chain expression plasmid resulted in the appearance of mu-chain in the media in a covalent complex with lambda-chain. An intracellular consequence of this was a reduction in the levels of BiP.mu-chain complex, and a diminished stimulation in the synthesis of the ER stress proteins. These results suggest that the BiP.mu-chain complex in the ER may be involved in the signaling pathway for the induction of ER stress proteins and may represent one regulatory mechanism operating in differentiating B-lymphocytes. PMID- 1939105 TI - Structure and expression of the gene encoding cystatin D, a novel human cysteine proteinase inhibitor. AB - A new member of the human cystatin multigene family has been cloned from a genomic library using a cystatin C cDNA probe. The complete nucleotide sequence of a 4.3-kilobase DNA segment, containing a complete gene with structure very similar to those of known Family 2 cystatin genes, was determined. The novel gene, called CST4, is composed of three exons and two introns. It contains the coding information for a protein of 142 amino acid residues, which has been tentatively called cystatin D. The deduced amino acid sequence includes a putative signal peptide and presents 51-55% identical residues with the sequences of either cystatin C or the secretory gland cystatins S, SN, or SA. The cystatin D sequence contains all regions of relevance for cysteine proteinase inhibitory activity and also the 4 cysteine residues that form disulfide bridges in the other members of cystatin Family 2. Northern blot analysis revealed that the cystatin D gene is expressed in parotid gland but not in seminal vesicle, prostate, epididymis, testis, ovary, placenta, thyroid, gastric corpus, small intestine, liver, or gall-bladder tissue. This tissue-restricted expression is in marked contrast with the wider distribution of all the other Family 2 cystatins, since cystatin C is expressed in all these tissues and the secretory gland cystatins are present in saliva, seminal plasma, and tears. Cystatin D, being the first described member of a third subfamily within the cystatin Family 2, thus appears to have a distinct function in the body in contrast to other cystatins. PMID- 1939106 TI - Apolipoprotein B mRNA editing is an intranuclear event that occurs posttranscriptionally coincident with splicing and polyadenylation. AB - The subcellular compartment in which apolipoprotein (apo) B mRNA is edited is unknown. We studied the site of endogenous apoB mRNA editing and correlated the extent of editing with mRNA maturation in the rat liver. RNA editing activity was demonstrated in both nuclear and cytoplasmic extracts. The specific activity of the editing activity was 5.5-fold higher in the nuclear extract, which was not accounted for by activators, inhibitors, or modulators. However, the total editing activity was 3.1 times higher in the cytoplasmic extract. Highly purified rat liver nuclear apoB mRNA contained 17.3 +/- 1.45% edited sequences compared with 56 +/- 2.5% and 62.15 +/- 6.2% edited sequences in hepatic total and polysomal RNAs, respectively. Because of the significant extent of editing of total nuclear RNA, we fractionated it into a poly(A-) and poly(A+) fraction. While the poly(A-) nuclear fraction contained only 10.4 +/- 1.1% edited sequences, which represents a maximum estimate, the poly(A+) nuclear apoB mRNA contained 50 +/- 1.8% edited sequences, a value very similar to that for polysomal RNA. By direct sequencing of cDNA and genomic clones, we found that as in the case of the human apoB gene, the rat apoB gene contains an intron 25 immediately upstream of the edited exon 26. Using this information, we developed a method to examine in a highly selective manner apoB mRNA that is present in the nucleus before splicing of intron 25 and after splicing of this intron. The unspliced nuclear pre-mRNA contained 7.4 +/- 0.2% edited sequences compared with 51.0 +/- 0.9% edited sequences in the spliced nuclear apoB mRNA. Furthermore, in the poly(A-) pool of apoB pre-mRNA, unspliced nuclear pre-mRNA contained hardly any (1.56%) edited sequences, and the spliced nuclear pre-mRNA contained 7.8 +/- 0.6% edited mRNA. In the poly(A+) fraction, unspliced nuclear pre-mRNA had 25.4 +/- 0.05% and spliced nuclear mRNA 53 +/- 0.6% of its apoB mRNA in an edited form. We conclude that in the rat liver apoB mRNA editing is not a cotransciptional event. It occurs posttranscriptionally, but the process is essentially complete in the spliced polyadenylated apoB mRNA before it leaves the nucleus. Little, if any, additional editing occurs in the cytoplasmic compartment. PMID- 1939107 TI - Molecular genetics of Alzheimer disease amyloid. PMID- 1939109 TI - The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, induces specific transcription by RNA polymerase III in Drosophila Schneider cells. AB - We have examined the ability of the tumor-promoting phorbol ester, 12-O tetradecanoylphorbol-13-acetate (TPA), to regulate RNA polymerase III gene expression in Drosophila. Using nuclear run-on assays, we detected a 3-5-fold increase in tRNA synthesis following treatment of Drosophila Schneider S2 cells with TPA, whereas transcription from the actin 5C, fos-, and jun-related antigen promoters was unaffected. This response is rapid and transient, peaking at about a 45-min exposure of the cells to TPA, and dissipating after 60 min. We have reproduced this stimulation in vitro. Extracts prepared from cells treated with TPA show an approximate 10-fold increase in specific transcription using a 5 S RNA and various tRNA gene templates. The nonspecific transcription by RNA polymerase III in these extracts, however, is essentially unchanged. Mixing the extracts derived from uninduced and induced cells suggests that the TPA stimulation observed may be due to the increase of a positive-acting factor. These results are the first to demonstrate that a phorbol ester can induce RNA polymerase III gene expression. The ability to reproduce this activation in vitro will now allow us to assess the role of the transcription components in this regulatory event, and the biochemical consequence of this signaling pathway. PMID- 1939108 TI - An inhibitory mutant of c-Raf-1 blocks v-Src-induced activation of the Egr-1 promoter. AB - The protein-tyrosine kinase activity of v-Src leads to the transcriptional activation of the mitogen-responsive transcription factor Egr-1. c-Raf-1 is a serine/threonine protein kinase that has been implicated in the transduction of signals induced by mitogens. The involvement of c-Raf-1 in v-Src-induced Egr-1 expression was investigated using an inhibitory mutant of c-Raf-1. We report here that expression of a kinase-defective mutant of c-Raf-1 inhibits v-Src-induced activation of the Egr-1 promoter. This inhibition is reversed by overexpression of wild type c-Raf-1. Consistent with an involvement of c-Raf-1 in a signaling pathway leading to Egr-1 expression, we find that v-Raf induces Egr-1 promoter activation. These data suggest that c-Raf-1 is a component in an intracellular signaling pathway initiated by v-Src leading to the induction of the mitogen responsive transcription factor Egr-1. PMID- 1939110 TI - A factor that activates oscillatory chloride currents in Xenopus oocytes copurifies with a subfraction of serum albumin. AB - Vertebrate blood sera contain a factor that elicits oscillatory chloride currents in Xenopus oocytes through activation of the phosphatidylinositol second messenger system. This factor was purified from rabbit and human sera by a sequence of Blue-Agarose chromatography, concanavalin A affinity chromatography, and hydroxyapatite fractionation, yielding a single active protein band (67 kDa). This protein is a subfraction of serum albumin, as revealed by its molecular mass, isoelectric properties, peptide maps, amino acid composition, and NH2 terminal sequence. Moreover, the factor could be purified with a monoclonal antibody to serum albumin and its ability to elicit oscillatory currents was inhibited by several polyclonal-monospecific antibodies to serum albumin. Various commercial high purity albumin preparations elicited oscillatory currents in oocytes. The activity of albumin was partially reduced by charcoal absorption and was greatly diminished when crystalline albumin was extracted with dry methanol. However, the activity was resistant to extraction with chloroform/ether, disulfide cleavage, and denaturation with 8 M urea, 6 M guanidinium chloride, and 1% sodium dodecyl sulfate. Trypsin or lipase treatment substantially reduced the potency of the active albumin, but neither treatment alone abolished the factor even after prolonged digestion. In contrast to serum or serum albumin, freshly collected blood plasma or purified plasma albumin did not evoke oscillatory currents. This indicates that some of the plasma albumin changes during blood coagulation and acquires a "factor" that makes it capable of activating the phosphatidylinositol-Ca2+ system in Xenopus oocytes. The serum factor also activates the phosphatidylinositol system in a variety of mammalian cells, suggesting that the modified albumin may play a role in cellular events related to tissue repair following injury. PMID- 1939111 TI - Biosynthesis of riboflavin. Studies on the mechanism of L-3,4-dihydroxy-2 butanone 4-phosphate synthase. AB - The riboflavin precursor, L-3,4-dihydroxy-2-butanone 4-phosphate, is formed from D-ribulose 5-phosphate by a single 24-kDa enzyme. Studies with various specifically 13C-labeled D-ribulose 5-phosphates as substrate showed that the carbon atoms 1-3 of the enzyme product correspond to carbon atoms 1-3 of the substrate, whereas C-4 of the product stems from C-5 of the substrate. Carbon atom 4 of the substrate is released as formate together with the hydrogen atom attached to it. The skeletal rearrangement which leads to the loss of C-4 and the direct linkage between C-3 and C-5 of the substrate is an intramolecular reaction. The hydrogen atom at C-3 of the enzyme product is introduced from solvent water. A reaction mechanism which is in agreement with all experimental data is proposed. PMID- 1939112 TI - Human red cell acid phosphatase (ACP1). The amino acid sequence of the two isozymes Bf and Bs encoded by the ACP1*B allele. AB - The pair of isozymes, Bf and Bs, encoded by the human red cell acid phosphatase ACP1*B allele has been sequenced. Similar but not identical primary structures were observed. Both isozymes consist of a single peptide chain of 157 amino acid residues, which is acetylated at the amino-terminal alanine residue. The Bf and Bs isozymes are not glycosylated, and the calculated molecular masses are 17,932 and 17,867 Da, respectively. They are identical except for the sequence segment 40-73, which is peculiar to the respective isozyme. This is consistent with our hypothesis that the two isozymes are generated as the result of alternative splicing of the primary RNA transcript. The finding of a signature sequence offers the basis for the characteristic differences in catalytic and molecular properties of the Bf and Bs isozymes. A high degree of homology was found between the Bs isozyme and the 18-kDa cytosolic acid phosphatase from bovine liver. No homology was observed with other sequenced proteins, and this establishes these low molecular weight acid phosphatases as products of a distinct gene family. PMID- 1939113 TI - The pH variation of steady-state kinetic parameters of site-specific Co(2+) reconstituted liver alcohol dehydrogenase. A mechanistic probe for the assignment of metal-linked ionizations. AB - To identify ionizations of the active site metal-bound water in horse liver alcohol dehydrogenase (alcohol:NAD+ oxidoreductase; EC 1.1.1.1), the pH, solvent isotope, temperature, and anion dependences of the steady-state kinetic parameters kcat and kcat/KM have been evaluated under initial velocity conditions for the native and the active site-specific Co(2+)-reconstituted enzyme. In the oxidation of benzyl alcohol, a bell-shaped pattern of four prototropic equilibria was observed under conditions of saturating concentrations of NAD+. It is shown that the ionizations governing kcat (pK1 congruent to 6.7, pK2 congruent to 10.6) belong to the ternary enzyme-NAD(+)-alcohol complex, whereas the ionizations governing kcat/KM (pK1' congruent to 7.5, pK2' congruent to 8.9) belong to the binary enzyme-NAD+ complex. The ionizations pK1 and pK1' are not influenced by metal substitution and are ascribed to His-51 on the basis of experimental estimates of their associated enthalpies of ionization. On the other hand, pK2 and pK2' are significantly decreased (delta pKa congruent to 1.0) in the Co(2+) enzyme and are attributed to the active site metal-bound water molecule. The shape of the pH profiles requires that the metal ion coordinates a neutral water molecule in the ternary enzyme-NAD(+)-alcohol complex under physiological conditions. The possible catalytic role of the water molecule within a pentacoordinate metal ion complex in the active site is discussed. PMID- 1939114 TI - On the mechanism and rate of substrate oxidation by amine oxidase from lentil seedlings. AB - The kinetics of reaction between lentil seedlings amine oxidase and two amine substrates, namely putrescine and dimethylaminomethylbenzylamine, have been studied by rapid mixing with diode array detection. In this way several wavelengths can be monitored at once allowing the simultaneous measurement of enzyme bleaching and formation of a yellow radical intermediate. The two substrates are oxidized at rates that differ by one order of magnitude in favor of putrescine. Of the individual five rate constants measured and/or calculated from the experimental ones, k2 alone, the monomolecular transformation of ES to EP accounts for this difference. The reoxidation step is instead not rate limiting and identical for the two substrates. PMID- 1939115 TI - Nucleoside hydrolase from Crithidia fasciculata. Metabolic role, purification, specificity, and kinetic mechanism. AB - Crithidia fasciculata cells grown on complex medium with added [8-14C, 5' 3H]inosine or [8-14C,5'-3H]adenosine metabolize greater than 50% of the salvaged nucleosides through a pathway involving N-glycoside bond cleavage. Cell extracts contain a substantial nucleoside hydrolase activity but an insignificant purine nucleoside phosphorylase. The nucleoside hydrolase has been purified 1000-fold to greater than 99% homogeneity from kilogram quantities of C. fasciculata. The enzyme is a tetramer of Mr 34,000 subunits to give an apparent holoenzyme Mr of 143,000 by gel filtration. All of the commonly occurring nucleosides are substrates. The Km values vary from 0.38 to 4.7 mM with purine nucleosides binding more tightly than the pyrimidines. Values of Vmax/Km vary from 3.4 x 10(3) M-1 s-1 to 1.7 x 10(5) M-1 s-1 with the pyrimidine nucleosides giving the larger values. The turnover rate for inosine is 32 s-1 at 30 degrees C. The kinetic mechanism with inosine as substrate is rapid equilibrium with random product release. The hydrolytic reaction can be reversed to give an experimental Keq of 106 M with H2O taken as unity. The product dissociation constants for ribose and hypoxanthine are 0.7 and 6.2 mM, respectively. Deoxynucleosides or 5' substituted nucleosides are poor substrates or do not react, and are poor inhibitors of the enzyme. The enzyme discriminates against methanol attack from solvent during steady-state catalysis, indicating the participation of an enzyme directed water nucleophile. The pH profile for inosine hydrolysis gives two apparent pKa values of 6.1 with decreasing Vmax/Km values below the pKa and a plateau at higher pH values. These effects are due to the pH sensitivity of the Vmax values, since Km is independent of pH. The pH profile implicates two negatively charged groups which stabilize a transition state with oxycarbonium character. PMID- 1939117 TI - Inhibition of the action of the stimulatory GDP/GTP exchange protein for smg p21 by the geranylgeranylated synthetic peptides designed from its C-terminal region. AB - smg p21B, a member of the ras p21-like small GTP-binding protein superfamily, undergoes post-translational modifications, which are geranylgeranylation of the cysteine residue in the C-terminal region followed by removal of the three C terminal amino acids (QLL) and the subsequent carboxyl methylation of the exposed prenylated cysteine residue. smg p21B has a polybasic region upstream of the prenylated cysteine residue. We have previously proposed that these C-terminal structures of smg p21B are essential for the action of its stimulatory GDP/GTP exchange protein, named GDP dissociation stimulator (GDS). We studied here which structure of the C-terminal region of smg p21B is important for its interaction with smg p21 GDS. For this purpose, we synthesized a peptide according to the C terminal structure of smg p21B, which was PGKARKKSSC-geranylgeranyl-carboxyl methyl, and its variously modified peptides and examined their ability to interact with smg p21 GDS and to interfere with the smg p21 GDS action to stimulate the GDP/GTP exchange reaction of smg p21B. The results indicate that the phosphorylated form of PGKARKKSSC-geranylgeranyl stoichiometrically interacts with smg p21 GDS, that the presence of the geranylgeranyl moiety is essential for, but not sufficient for, the smg p21 GDS action, and that the presence of the methyl moiety, removal of the three C-terminal amino acids, and the presence of the polybasic amino acids also affect the smg p21 GDS action. It is likely that all the steps of the post-translational processing and presence of the polybasic region in the C-terminal region of smg p21B are related to its interaction with smg p21 GDS. PMID- 1939116 TI - Crystal structures of the apo- and holomutant human lysozymes with an introduced Ca2+ binding site. AB - The three-dimensional structures of apo- and holomutant human lysozymes (D86/92 lysozyme), in which a calcium binding site was designed and created for enhancing molecular stability by replacing both Gln86 and Ala92 with aspartic acids, were refined at 1.8-A resolution by x-ray crystallography. The overall structures and crystallographic thermal factors of all three proteins, the apo-, holo-D86/92, and the wild-type human lysozymes, were essentially identical; these results showed that the introduction of the calcium binding site did not affect either the overall structure or molecular rigidity of the proteins. However, structure analyses of the apo-D86/92 lysozyme revealed that the mutations affected the side chain conformation of residue 86 and hydrogen networks between the protein and the internal solvent molecules. In the structure of the holo-D86/92 lysozyme, seven oxygen ligands formed a slightly distorted pentagonal bipyramid around the calcium ion, indicating that the coordination around the calcium ion was quite similar to that in baboon alpha-lactalbumin. The pentagonal bipyramid coordination could be one of the most widely found and appropriate calcium binding schemes in proteins. PMID- 1939118 TI - Physical characterization and crystallization of the carbohydrate-recognition domain of a mannose-binding protein from rat. AB - A portion of rat mannose-binding protein A (MBP-A), a Ca(2+)-dependent animal lectin, has been overproduced in a bacterial expression system, biochemically characterized, and crystallized. A fragment corresponding to the COOH-terminal 115 residues of native MBP-A, produced by subtilisin digestion of the bacterially expressed protein, contains the carbohydrate-recognition domain (CRD). Gel filtration, chemical cross-linking, and crystallographic self-rotation function analyses indicate that the subtilisin fragment is a dimer, although the complete bacterially expressed fragment, containing the neck and CRD of MBP-A, is a trimer. Crystals of the minimal CRD, obtained only as a complex with a Man6GlcNAc2Asn glycopeptide, diffract to Bragg spacings of at least 1.7 A. Several trivalent lanthanide ions (Ln3+) can substitute for Ca2+, as assessed by their ability to support carbohydrate binding and to protect the CRD from proteolysis in a manner similar to that observed for Ca2+. These assays indicate that Ln2+ binds about 30 times more tightly than Ca2+ to the CRD, and that two Ca2+ or Ln3+ bind to each monomer, a result confirmed by determination of the Ho3+ positions in a Ho(3+)-containing crystal of the CRD. Crystals grown in the presence of Ln3+ belong to different space groups from those obtained with Ca2+ and are therefore not useable for traditional crystallographic phase determination methods, but are well-suited for high resolution structure determination by multiwavelength anomalous dispersion phasing. PMID- 1939119 TI - Reactions of lignin peroxidase compounds I and II with veratryl alcohol. Transient-state kinetic characterization. AB - Stopped-flow techniques were utilized to investigate the kinetics of the reaction of lignin peroxidase compounds I and II (LiPI and LiPII) with veratryl alcohol (VA). All rate data were collected from single turnover experiments under pseudo first-order conditions. The reaction of LiPI with VA strictly obeys second-order kinetics over the pH range 2.72-5.25 as demonstrated by linear plots of the pseudo first-order rate constants versus concentrations of VA. The second-order rate constants are strongly dependent on pH and range from 2.62 x 10(6) M-1 s-1 (pH 2.72) to 1.45 x 10(4) M-1 s-1 (pH 5.25). The reaction of LiPII and VA exhibits saturation behavior when the observed pseudo first-order rate constants are plotted against VA concentrations. The saturation phenomenon is quantitatively explained by the formation of a 1:1 LiPII-substrate complex. Results of kinetic and rapid scan spectral analyses exclude the formation of a LiPII-VA cation radical complex. The first-order dissociation rate constant and the equilibrium dissociation constant for the LiPII reaction are also pH dependent. Binding of VA to LiPII is controlled by a heme-linked ionizable group of pKa approximately 4.2. The pH profiles of the second-order rate constants for the LiPI reaction and of the first-order dissociation constants for the LiPII reaction both demonstrate two pKa values at approximately 3.0 and approximately 4.2. Protonated oxidized enzyme intermediates are most active, suggesting that only electron transfer, not proton uptake from the reducing substrate, occurs at the enzyme active site. These results are consistent with the one-electron oxidation of VA to an aryl cation radical by LiPI and LiPII. PMID- 1939121 TI - The role of cysteine 206 in allosteric inhibition of Escherichia coli citrate synthase. Studies by chemical modification, site-directed mutagenesis, and 19F NMR. AB - Escherichia coli citrate synthase is strongly and specifically inhibited by NADH, but this inhibition can be prevented by reacting the enzyme with Ellman's reagent. We have now labeled the single reactive cysteine covalently with monobromobimane and isolated and sequenced the bimane-containing cyanogen bromide peptide and identified the cysteine as Cys-206. Modeling studies suggest that this residue is on the subunit surface, 25-30 A from the active site. Mutation of Cys-206 to serine (C206S), or of Gly-207 to alanine (E207A), weakened NADH binding and inhibition; when these mutations were present together, NADH binding was weaker by 18-fold and inhibition by 250-fold. The mutations also had small effects on substrate binding at the active site. Cys-206 of wild type enzyme and of the mutant E207A was alkylated with 1,1,1-trifluorobromoacetone and the environment of the fluorine nuclei studied by 19F NMR. With wild type enzyme, the NMR spectrum consisted of two peaks of about equal intensity but different line widths, at -8.65 ppm (line width 11.2 +/- 0.5 Hz) and -7.6 ppm (line width 57 +/- 4 Hz). As the labeled wild type citrate synthase was titrated with KCl, the narrow peak converted to the broad one. The same range of KCl concentrations was needed for this conversion as for the allosteric activation of E. coli citrate synthase. The E207A mutant gave the broader NMR peak almost exclusively. We propose that the fluorine label in wild type citrate synthase exists in two conformational states with different mobilities, exchanging slowly on the NMR time scale, and that treatment with KCl, or truncation of the Glu-207 side chain by mutagenesis, stabilizes one of these states. Consistent with this explanation is the finding that Cys-206 reacts more quickly with Ellman's reagent in the presence of KCl, and that this rate is faster yet in the E207A mutant. PMID- 1939120 TI - Generation of the mitochondrial permeability transition does not involve inhibition of lysophospholipid acylation. Acyl-coenzyme A:1-acyllysophospholipid acyltransferase activity is not found in rat liver mitochondria. AB - The possible involvement of acyl-coenzyme A:1-acyllysophospholipid acyltransferase activity and phospholipid acylation-deacylation cycles in regulating the mitochondrial permeability transition have been examined by direct methods. 1-Acyllysophospholipid acyltransferase activity found in mitochondrial preparations obtained by differential centrifugation is inhibited by several transition-inducing agents and by glutathione disulfide. However, marker enzyme analysis employing mitochondria prepared by Percoll density gradient centrifugation or fractionated by a shear force-dependent method indicate that this activity is associated with contaminating microsomes and not with mitochondria. The absence of phospholipid acylation-deacylation cycles in isolated mitochondria is demonstrated by the absence of 18O incorporation from H2(18)O into phospholipid acylester carbonyl groups, confirming conclusions arrived at from marker enzyme data by a definitive independent approach. Mitochondria prepared by differential centrifugation and Percoll density gradient centrifugation are shown to be equivalent in requirements for induction of the permeability transition and the apparent rate of this process. It is concluded that 1-acyllysophospholipid acyltransferase activity and phospholipid acylation deacylation cycles are not factors regulating the transition in isolated mitochondria. However, mitochondrial phospholipase A2 activity remains as a potential regulating factor, whereas the action of transition-inducing agents on microsomal 1-acyllysophospholipid acyltransferase may be important in mechanisms of cell injury. PMID- 1939122 TI - Initiation of protein synthesis in animal mitochondria. Purification and characterization of translational initiation factor 2. AB - Bovine liver mitochondrial translational initiation factor 2 (IF-2mt) has been purified to near homogeneity. The scheme developed results in a 24,000-fold purification of the factor with about 26% recovery of activity. SDS polyacrylamide gel electrophoresis indicates that IF-2mt has a subunit molecular mass of 85 kDa. IF-2mt promotes the binding of formyl(f)Met-tRNA to mitochondrial ribosomes but is inactive with the nonformylated derivative. IF-2mt is active on chloroplast 30 S ribosomal subunits, but IF-2chl has no activity in promoting fMet-tRNA binding to animal mitochondrial ribosomes. IF-2mt is sensitive to elevated temperatures and is inactivated by treatment with N-ethylmaleimide. It is partially protected from heat and N-ethylmaleimide inactivation by the presence of either GTP or GDP suggesting that guanine nucleotides may bind to this factor directly. The binding of fMet-tRNA to mitochondrial ribosomes requires the presence of GTP and is inhibited by GDP. DeoxyGTP is very effective in replacing GTP in promoting fMet-tRNA binding to ribosomes and some activity is also observed with ITP. No activity is observed with ATP, CTP, or UTP. Nonhydrolyzable analogs of GTP can promote formation of both 28 S and 55 S initiation complexes indicating that GTP hydrolysis is not required for subunit joining in the animal mitochondrial system. PMID- 1939124 TI - Identification by photoaffinity labeling of fatty acid-binding protein as a potential warfarin receptor in rat liver. AB - Two different photoaffinity analogs of 4-hydroxy coumarin, 3-(p-azidobenzyl)-4 hydroxycoumarin (AzBHC) and 3-(4-azido-5-iodosalicylamido)-4-hydroxycoumarin (AzISAHC), are being used in the identification of warfarin-binding proteins present in mammalian tissue (Myszka, D. G., and Swenson, R. P. (1990) Biochem. Biophys. Res. Commun. 172, 415-422; Myszka, D. G., and Swenson, R. P. (1991) J. Biol. Chem. 266, 4789-4797). In this study, [14C]AzBHC, but not [125I]AzISAHC, was observed to specifically label a 15,000-dalton protein present in both the microsomal and cytosolic fractions of rat liver. Pretreatment of the crude protein samples with warfarin or dicoumarol completely protected the 15-kDa protein from modification by [14C]AzBHC, indicating that this photoaffinity reagent is specifically labeling a coumarin-binding protein. 4-Hydroxycoumarin itself and AzISAHC were unable to block the incorporation of this photoaffinity probe. The 15-kDa protein was isolated by two-dimensional electrophoresis and subjected to amino-terminal sequence analysis. The first 20 amino acid residues analyzed were found to be identical with the amino-terminal sequence of rat liver fatty acid-binding protein (L-FABP) (Gordon J. I., Alpers, D. H., Ockner, R. K., and Strauss, A. W. (1983) J. Biol. Chem. 258, 3356-3363). Photoaffinity labeling and protection experiments carried out on purified preparations of L-FABP paralleled the labeling results obtained in the microsomes and cytosol, confirming that L-FABP is capable of specifically binding AzBHC, warfarin, and dicoumarol. Oleic acid, an established ligand for L-FABP, can compete with the binding of the photoaffinity probe; however, it was less effective in protecting the protein than warfarin. The specificity of labeling of crude liver fractions by warfarin photoaffinity analogs reported here as well as the high concentration of FABP in liver tissue together suggest that this protein may represent a major hepatic receptor responsible for the uptake and/or transport of various oral 4 hydroxycoumarin-based anticoagulant drugs. PMID- 1939123 TI - The cloning and expression of a gene encoding Old Yellow Enzyme from Saccharomyces carlsbergensis. AB - We have identified a gene that encodes Old Yellow Enzyme in brewer's bottom yeast. The open reading frame encodes a polypeptide of 400 amino acids with Mr = 45,021. Using the T7 RNA polymerase system, recombinant enzyme was expressed in Escherichia coli. 17 mg of Old Yellow Enzyme was obtained from a 3-liter cell culture, and the recombinant enzyme had NADPH oxidase activity. On fast protein liquid chromatography separation, the recombinant enzyme showed a single large peak, while native enzyme from brewer's bottom yeast separated into five fractions on fast protein liquid chromatography. Southern blot analysis showed that there are at least two Old Yellow Enzyme genes in brewer's bottom yeast genomic DNA. These results suggest that the heterogeneity of Old Yellow Enzyme in Saccharomyces carlsbergensis is due to the presence of multiple genes. PMID- 1939126 TI - Arrangement of the substrates at the active site of brain pyridoxal kinase. AB - The distances between enzyme-bound paramagnetic CrATP (a stable, beta, gamma bidentate complex of Cr3+ and ATP) at the active site of sheep brain pyridoxal kinase and the protons of bound inhibitor 4-dPyr (4-deoxypyridoxine) were determined in the ternary enzyme-CrATP.4-dPyr complex by measuring the paramagnetic effects of Cr3+ on the longitudinal relaxation rates (1/T1p) of the protons of 4-dPyr. The correlation time for the Cr(3+)-4-dPyr dipolar interaction on the enzyme was estimated as 1.59 ns by the frequency dependence of 1/T1p of water protons. Temperature dependence of 1/T1p values indicated the fast exchange of 4-dPyr from the paramagnetic enzyme.CrATP.4-dPyr complex; hence the measured 1/T1p values can be used for metalnucleus distance determinations. The distances from the Cr3+ of the enzyme-bound CrATP to the 2-methyl (7.19 A), 4-methyl (7.18 A), and H6 proton (6.18 A) of the 4-dPyr are too great to permit a direct coordination of any group from 4-dPyr. However, these distances can be built into a model in which phosphorus of the gamma-phosphoryl group of ATP is 4 A away from the oxygen atom of the 5-CH2OH group of the 4-dPyr. This suggests that phosphorylation of pyridoxal can occur via direct transfer of the phosphoryl group between the bound substrates at the active site of pyridoxal kinase. PMID- 1939125 TI - Overexpression of seleno-glutathione peroxidase by gene transfer enhances the resistance of T47D human breast cells to clastogenic oxidants. AB - The role of seleno-glutathione peroxidase (GSHPx; EC 1.11.1.9) in the cellular defense against oxidative stress was selectively investigated in novel cell models. Expression vectors designed to overexpress human GSHPx efficiently in a broad range of mammalian cells were used to transfect T47D human breast cells which contain very low levels of endogenous GSHPx. Several stable transfectants expressing GSHPx to various extents, up to 10-100 times more than parental cells, were isolated and characterized. Growth inhibition kinetics following transient exposure to increasing concentrations of H2O2, cumene hydroperoxide or menadione (an intracellular source of free radicals and reactive oxygen intermediates) showed that transfectants overexpressing GSHPx were considerably more resistant than control T47D cell derivatives to each of these oxidants. A sensitive DNA end labeling procedure was used as a novel approach to compare relative extents of DNA strand breakage in these cells. In contrast to the extensive DNA damage induced in control transfectants by 1-h exposure to cytotoxic concentrations of menadione, the extent of DNA breakage detected in GSHPx-rich transfectants was remarkably reduced (6- to 9-fold, p less than 0.005). PMID- 1939128 TI - Site-directed mutagenesis of Escherichia coli succinyl-CoA synthetase. Histidine 142 alpha is a facilitative catalytic residue. AB - There are 11 histidine residues in Escherichia coli succinyl-CoA synthetase. His 246 alpha is well established as the phosphorylation site of the enzyme. Replacement of this histidine by asparagine (Mann, C. J., Mitchell, T., and Nishimura, J. S. (1991) Biochemistry 30, 1497-1503) or by aspartic acid (Majumdar, R., Guest, J. R., and Bridger, W. A. (1991) Biochim. Biophys. Acta 1076, 86-90) through site-directed mutagenesis resulted in complete loss of enzyme activity. Chemical modification experiments suggested a second histidine at the active site (Collier, G. E., and Nishimura, J. S. (1979) J. Biol. Chem. 254, 10925-10930). In the present study, we have changed His-142 alpha to an asparagine residue using the technique of site-directed mutagenesis and have purified the mutant enzyme to homogeneity. The resulting mutant enzyme is practically devoid of enzyme activity but can be thiophosphorylated with adenosine 5'-O-(thiotriphosphate) and dethiophosphorylated with ADP at rates that are significantly faster than those with wild type enzyme. The observation that phosphorylated mutant enzyme can be dephosphorylated with succinate and with succinate plus desulfo-CoA at rates comparable with those with wild type enzyme suggests that mutant enzyme can bind succinate and CoA. Dethiophosphorylation of the enzyme in the presence of CoA plus succinate proceeds much faster with wild type than with mutant. While there was no significant change in KCoA or Ksuccinate, the turnover number for dethiophosphorylation of the mutant was 10 fold lower. These data are consistent with location of His-142 alpha at the active site and a facilitative role for this residue in catalysis. PMID- 1939127 TI - Purification and characterization of an endotoxin-binding protein with protease inhibitory activity from Limulus amebocytes. AB - Using a lipopolysaccharide affinity column and ion exchange chromatography, a 12 kDa protein has been purified from Limulus amebocytes. In solid phase binding assays, the radiolabeled protein binds specifically to lipopolysaccharide (LPS) with a Kd value on the order of 10(-7) M. A cDNA coding for this protein has been isolated and sequenced. The amino acid sequence deduced from the cDNA indicates that this protein shares no sequence homology with LPS-binding proteins isolated from different species of vertebrates (Schumann, R. R., Leong, S. R., Flaggs, G. W., Gray, P. W., Wright, S. D., Mathison, J. C., Tobias, P. S., and Ulevitch, R. J. (1990) Science 249, 1429-1431) and invertebrates (Aketagawa, J., Miyata, T., Ohtsubo, S., Nakamura, T., Morita, T., Hayashida, H., Miyata, T., Iwanaga, S., Takao, T., and Shimonishi, Y. (1986) J. Biol. Chem. 261, 7357-7365). The binding to LPS can be displaced by the unlabeled 12-kDa protein, polymyxin B, lipid A, and to a lesser extent by D-glucosamine. In whole cell binding assays, the 12-kDa protein has also been shown to bind to Escherichia coli. Using both [14C]casein and a synthetic substrate, the protein has been shown to inhibit the proteolytic activity of trypsin, with an IC50 of approximately 10(-7) M. In the presence of LPS, the antitryptic acitivity of the Limulus endotoxin-binding protein-protease inhibitor remains unaffected. The protein is a major component of the cytoplasmic proteins (1%). Immunocytochemical analysis reveals that this protein exists in the secretory granules of the amebocytes where enzymes and substrates for the clotting cascade reside. Based on the unusual dual functional properties, the newly isolated protein was named a "Limulus endotoxin-binding protein-protease inhibitor" (LEBP-PI). PMID- 1939129 TI - Expression of insulin-like growth factor I in developing lens is compartmentalized. AB - We, and others, have recently reported that insulin-like growth factor I (IGF-I) mRNA is expressed in multiple tissues during embryogenesis and in whole embryos during early organogenesis. Therefore, it is likely that, in addition to any effect on embryo growth, IGF-I plays a paracrine/autocrine role in development. The embryonic chicken lens, an avascular organ composed by a single type of cell that undergoes differentiation in vivo and in vitro, is an ideal model to characterize the paracrine/autocrine action of IGF-I. The lens cells express IGF I receptors, and respond to exogenous IGF-I with induction of fiber cells differentiation and stimulation of delta-crystallin gene transcription. Whether embryonic lens cells express IGF-I was uncertain. In the present study, we used a sensitive semiquantitative method (reverse transcription of RNA followed by amplification with the polymerase chain reaction) to analyze IGF-I gene expression. An amplified product of the expected length (209 base pairs) was found in days 8, 12, 15, and 19 lenses. At all embryo ages studied, the product was more readily detected in the lens than in the liver, while in eye tissues (excluding lens), IGF-I expression was relatively high. After microdissection of the epithelial cells from the fully differentiated fiber cells, IGF-I expression was detected exclusively in the epithelial cells. IGF-I immunoactivity was found using high performance liquid chromatography followed by radioimmunoassay in the days 8-19 lens extracts, and in primary cultures of isolated epithelial cells. Our previous and present findings show that the lens has all the elements for IGF I autocrine/paracrine action in development. PMID- 1939130 TI - Purification and cDNA cloning of rat 6-pyruvoyl-tetrahydropterin synthase. AB - 6-Pyruvoyl-tetrahydropterin synthase, which catalyzes the second step in the biosynthesis of tetrahydrobiopterin, was purified approximately 18,000-fold to apparent homogeneity from rat liver. The molecular mass of the native enzyme was estimated to be 83 kDa by gel filtration. The enzyme showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis corresponding to a molecular mass of 17 kDa. Up to 24 residues of the NH2-terminal sequence were determined by Edman degradation, which released a single amino acid at each step. These results indicate that the enzyme consists of identical subunits. The purified enzyme was digested with lysyl endopeptidase or V8 protease, and 11 peptide fragments were isolated. On the basis of the sequences of these peptides, oligonucleotides were synthesized and used to screen a rat liver cDNA library, and one cDNA clone was isolated. The complete nucleotide sequence of the 1176 base pair cDNA was then determined. The deduced amino acid sequence contained 144 amino acid residues, but a NH2-terminal four-amino acid sequence was not found in the purified protein. Therefore, the mature protein consists of 140 amino acids. A single mRNA band of 1.3 kilobases was obtained by RNA blot analysis of rat liver. The predicted amino acid sequence of 6-pyruvoyl-tetrahydropterin synthase was compared with the Protein Sequence Database of the National Biomedical Research Foundation, revealing significant local similarity to large T antigens from the polyomavirus family. PMID- 1939132 TI - Carboxypeptidase Y stability. AB - The stability of carboxypeptidase Y under different reaction conditions and in the presence various cosolvents was investigated. Loss of both hydrolysis and transpeptidation activities was monitored. Incubation of the enzyme at high temperatures or high pH resulted in the loss of both activities at the same rate. Addition of ammonium sulfate resulted in loss of transpeptidation activity but not hydrolysis activity. Addition of some organic solvents or Triton X-100 to the incubation mixture resulted in loss of both activities with transpeptidation being lost more rapidly than hydrolysis activity, while other organic solvents were observed to eliminate both activities entirely. Incubation of the enzyme in the presence of sodium dodecyl sulfate resulted in a decrease in both activities but hydrolysis was lost more rapidly than the transpeptidase activity. Implications of the observed preferential loss of activities to the labeling of peptides and proteins is discussed. PMID- 1939131 TI - cDNA and deduced amino acid sequence of a mouse DNA repair enzyme (APEX nuclease) with significant homology to Escherichia coli exonuclease III. AB - We purified a mouse DNA repair enzyme having apurinic/apyrimidinic endonuclease, DNA 3'-phosphatase, 3'-5'-exonuclease and DNA 3' repair diesterase activities, and designated the enzyme as APEX nuclease. A cDNA clone for the enzyme was isolated from a mouse spleen cDNA library using probes of degenerate oligonucleotides deduced from the N-terminal amino acid sequence of the enzyme. The complete nucleotide sequence of the cDNA (1.3 kilobases) was determined. Northern hybridization using this cDNA showed that the size of its mRNA is about 1.5 kilobases. The complete amino acid sequence for the enzyme predicted from the nucleotide sequence of the cDNA (APEX nuclease cDNA) indicates that the enzyme consists of 316 amino acids with a calculated molecular weight of 35,400. The predicted sequence contains the partial amino acid sequences determined by a protein sequencer from the purified enzyme. The coding sequence of APEX nuclease was cloned into pUC18 SmaI and HindIII sites in the control frame of the lacZ promoter. The construct was introduced into BW2001 (xth-11, nfo-2) strain cells of Escherichia coli. The transformed cells expressed a 36.4-kDa polypeptide (the 316 amino acid sequence of APEX nuclease headed by the N-terminal decapeptide of beta-galactosidase) and were less sensitive to methyl methanesulfonate than the parent cells. The fusion product showed priming activity for DNA polymerase on bleomycin-damaged DNA and acid-depurinated DNA. The deduced amino acid sequence of mouse APEX nuclease exhibits a significant homology to those of exonuclease III of E. coli and ExoA protein of Streptococcus pneumoniae and an intensive homology with that of bovine AP endonuclease 1. PMID- 1939133 TI - Structural requirements for nucleophilic substrates of carboxypeptidase Y. AB - The composition and structural aspects of the amino and carboxylic acid groups required for incorporation into peptides by transpeptidation and inhibition of hydrolysis in carboxypeptidase Y-catalyzed reactions were studied. Separation of these two groups by even one carbon prevents incorporation by transpeptidation and does not inhibit incorporation of other amino acids into model peptides. Substitution of phosphonic or sulfonic acids for the carboxylic acid group also results in loss of incorporation by transpeptidation. Only the sulfonic acid analog of glycine causes inhibition of hydrolysis and this inhibition is lost when serine is included in the reaction. d-Serine is not incorporated by carboxypeptidase Y, and its presence in the reaction mixture does not inhibit the incorporation of the L-isomer. PMID- 1939134 TI - Different amino acid substitutions at the same position in the nucleotide-binding site of aspartate transcarbamoylase have diverse effects on the allosteric properties of the enzyme. AB - Site-directed mutagenesis was used to determine how the allosteric properties of aspartate transcarbamoylase (ATCase) are affected by amino acid replacements in the nucleotide binding region of the regulatory polypeptide chains. Amino acid substitutions were made for both Lys-60 and Lys-94 in the regulatory chain since those residues have been implicated by x-ray diffraction studies, chemical modification experiments, and site-directed mutagenesis as playing a role in binding CTP and ATP. Lys-60 was replaced by His, Arg, Gln, and Ala, and Lys-94 was changed to His. These mutant forms of ATCase exhibit bewildering changes in the allosteric properties compared to the wild-type enzyme as well as altered affinities for the nucleotide effectors. The enzyme containing His-60 lacks both homotropic and heterotropic effects and exhibits no detectable binding of nucleotides. In contrast, the holoenzymes containing either Gln-60 or Arg-60 retain both homotropic and heterotropic effects. Replacement of Lys-60 by Ala yields a derivative exhibiting altered heterotropic effects involving insensitivity to CTP and activation by ATP. The mutant enzyme containing His-94 in place of Lys exhibits cooperativity with reduced affinity for nucleotides. The multiple substitutions at Lys-60 in the nucleotide binding region of the regulatory chains of ATCase demonstrate that different amino acids in the same location can alter indirectly the delicate balance of interactions responsible for the allosteric properties of ATCase. The studies show that it is hazardous and frequently unwarranted from single amino acid replacements of a specific residue to attribute to that residue the properties observed for the wild-type enzyme. PMID- 1939135 TI - Identification of the human platelet GTPase activating protein for the CDC42Hs protein. AB - The CDC42Hs protein appears to be an isoform of the ras-related GTP-binding protein G25K and is an apparent human homolog of the Saccharomyces cerevisiae cell-division-cycle protein, CDC42Sc. In this study, we report the identification of a GTPase-activating protein (GAP) for CDC42Hs from human platelets (designated from here on as CDC42Hs-GAP). The CDC42Hs-GAP activity was solubilized from platelet membranes, recovered through successive chromatography steps (the final step being Mono-Q chromatography), and purified approximately 3500-fold. The CDC42Hs-GAP activity appeared to correspond to a polypeptide with an apparent Mr of approximately 25,000. The GTPase activities of the purified human platelet CDC42Hs, the Escherichia coli-recombinant CDC42Hs, and the Spodoptera frugiperda recombinant GTP-binding proteins are all stimulated by the CDC42Hs-GAP to identical extents, which indicates that the recombinant CDC42Hs proteins are as effective as the native human platelet protein in coupling to the GAP. However, a mutant form of the E. coli-recombinant CDC42Hs which contains a valine residue at position 12 (CDC42HsVal-12) has a significantly reduced intrinsic GTPase activity (relative to the wild type CDC42HsGly-12) which is not stimulated by the CDC42Hs GAP. The CDC42Hs-GAP also does not stimulate the GTPase activities of the ras or rap GTP-binding proteins; however, it is capable of a weak stimulation of the GTPase activity of mammalian rho. Based on the apparent similarities in the molecular size of the CDC42Hs- and rho-GAPs (i.e. 25-30 kDa), and the cross reactivity of rho with the CDC42Hs-GAP, it seems likely that the CDC42Hs- and rho GAPs will constitute a specific subclass of the ras-related GAP superfamily. PMID- 1939136 TI - Membrane insertion of the Escherichia coli MalF protein in cells with impaired secretion machinery. AB - The MalF protein is an integral membrane protein of Escherichia coli containing eight membrane-spanning stretches and a large periplasmic domain of approximately 180 amino acids. We have asked whether this protein is dependent for its membrane insertion on the bacterial secretion machinery specified by the sec genes. Using azide to inhibit the SecA protein and sec mutants to reduce the functioning of the machinery, we have studied the membrane assembly of MalF and beta galactosidase and alkaline phosphatase fusions to MalF. In no case did we see an effect of reducing sec gene function on the insertion of MalF or fusion proteins. Selection for mutants that would cause internalization of a MalF-beta galactosidase hybrid protein yielded no mutations in sec genes. Our results suggest that MalF can assemble in the membrane independently of the bacterial secretion machinery. PMID- 1939137 TI - Amino acid sequence of long chain alpha-hydroxy acid oxidase from rat kidney, a member of the family of FMN-dependent alpha-hydroxy acid-oxidizing enzymes. AB - The complete amino acid sequence of rat kidney long chain alpha-hydroxy acid oxidase has been determined by microsequencing, using a number of standard enzymatic and chemical cleavages. Peptides were purified by high pressure liquid chromatography or by gel electrophoresis followed by electrotransfer. The sequence comprises 352 residues and ends with a peroxisomal targeting sequence SRL. The present work definitely establishes that hydroxy acid oxidase is a member of the family of FMN-dependent alpha-hydroxy acid-oxidizing enzymes. The family includes lactate oxidase, short chain alpha-hydroxy acid oxidase (glycolate oxidase), flavocytochrome b2, and mandelate dehydrogenase. There are altogether 45 totally conserved positions among the six sequences known. The sequence similarities are analyzed in light of the known three-dimensional structure of flavocytochrome b2 and glycolate oxidase. It is concluded that long chain hydroxy acid oxidase should be folded as a beta 8 alpha 8 barrel and should dehydrogenate alpha-hydroxy acids according to the same chemical mechanism as other enzymes of the family, in spite of a Tyr----Phe substitution at the active site. PMID- 1939138 TI - Kluyveromyces bulgaricus yeast lectins. Isolation of two galactose-specific lectin forms from the yeast cell wall. AB - Incubation of galactose treated Kluyveromyces bulgaricus yeast cells in EDTA/phosphate-buffered saline led to an extract possessing hemagglutinating and yeast flocculating properties. Purification of this extract by affinity chromatography and gel filtration gave two lectin forms, Kb-CWL I and Kb-CWL II, with an apparent molecular mass of 38,000 and 150,000 Da, respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that Kb-CWL I and Kb CWL II were dimeric and octameric of a subunit of 18,900 Da. At high concentration, purified Kb-CWL I associated to give Kb-CWL II. This association seemed to be independent on pH. The two lectin forms were glycoproteins, the peptide counterpart was very rich in Lys, Glu, and Gly, and the carbohydrate part represented 1% of the whole molecule and was composed of Glc, Man, and Ara. The two lectin forms (KB-CWL I and Kb-CWL II) agglutinated human red blood cells and flocculated EDTA-treated K. bulgaricus yeast cells. The activity of both lectin forms required Ca2+ ions, while Sr2+ showed some competitive inhibition. Optimal activity was obtained within a pH range of 4-6.5 for both forms. Temperatures of 80-90 degrees C for 20 min, or proteolytic treatment reduced irreversibly the activity of Kb-CWL I and Kb-CWL II. The role of the cell wall phosphopeptidomannan as a ligand and a potential physiological receptor of these lectin forms was demonstrated. PMID- 1939139 TI - Interferon-alpha treatment of Daudi cells down-regulates the octamer binding transcription/DNA replication factors Oct-1 and Oct-2. AB - Treatment of Daudi cells with alpha-interferon (alpha-IFN) results in a considerable decrease in the levels of the octamer-binding DNA replication/transcription factors Oct-1 and Oct-2 and specifically inhibits gene expression by octamer-containing promoters. The inhibitory effect on octamer binding proteins also occurs after culturing cells with phorbol 12-myristate 13 acetate but it does not occur following alpha-IFN treatment of an alpha-IFN resistant variant of the Daudi cell line or of HeLa cells. We discuss the potential role of the decreased levels of octamer-binding proteins in the inhibition of cell proliferation. PMID- 1939140 TI - Locating a low density lipoprotein-targeting domain of human apolipoprotein B-100 by expressing a minigene construct in transgenic mice. AB - Through its interaction with the low density lipoprotein (LDL) receptor, apolipoprotein (apo) B-100 is a major determinant of LDL metabolism and plasma cholesterol. Its receptor binding ability is conformation-dependent and requires its expression on the right lipoprotein particles. The structural signal that targets apoB-100 to LDL is unknown. We have microinjected a human apoB-100 minigene construct comprising less than 25% of the apoB-100 sequence driven by the natural apoB promoter to produce transgenic mice. The transgene product was expressed at a high level and was present exclusively in the LDL of these animals. Analysis of the responsible sequence (residues 2878-3925 of apoB-100) reveals unique structural features that may be important in its role as an LDL targeting domain. PMID- 1939141 TI - Coexistence of the genes for putrescine transport protein and ornithine decarboxylase at 16 min on Escherichia coli chromosome. AB - The nucleotide sequence of one of the putrescine transport operons (pPT71), located at 16 min of the Escherichia coli chromosome, was determined. It contained the genes for an induced ornithine decarboxylase and a putrescine transport protein. The gene for the ornithine decarboxylase contained a 2,196 nucleotide open reading frame encoding a 732-amino acid protein whose calculated Mr was 82,414, and the predicted amino acid sequence from the open reading frame had 65% homology with that of a constitutive ornithine decarboxylase encoded by the gene at 64 min. The ornithine decarboxylase activity was observed in the cells carrying pPT71 cultured at pH 5.2, but not in the cells cultured at pH 7.0. The gene for the putrescine transport protein contained a 1,317-nucleotide open reading frame encoding a 439-amino acid protein whose calculated Mr was 46,494. The hydropathy profile of the putrescine transport protein revealed that it consisted of 12 putative transmembrane spanning segments linked by hydrophilic segments of variable length. The transport protein was in fact found in the membrane fraction. When the gene for the putrescine transport protein was linked to the tet promoter of the vector instead of its own promoter, the putrescine transport activity increased greatly. The results suggest that the gene expression of the operon is repressed strongly under standard conditions. PMID- 1939142 TI - Characteristics of the gene for a spermidine and putrescine transport system that maps at 15 min on the Escherichia coli chromosome. AB - The nucleotide sequence of the gene for the spermidine and putrescine transport system that maps at 15 min on the Escherichia coli chromosome was determined. It contained four open reading frames encoding A, B, C, and D proteins. By making several subclones, we showed that expression of all the four proteins was necessary for maximal spermidine and putrescine transport activity. A single transport system was involved in the transport of both spermidine and putrescine. The A protein (Mr 43K) was found to be associated with membranes, as shown by Western blot analysis of the cell fractions. In addition, it had consensus amino acid sequences for the nucleotide binding site. B (Mr 31K) and C (Mr 29K) proteins consisted of six putative transmembrane spanning segments linked by hydrophilic segments of variable length as shown by cell localization of the proteins synthesized in maxicells and by hydropathy profiles. D protein (Mr 39K) was inferred to be a polyamine binding protein existing in a periplasmic fraction from the results of Western blot analysis of the cell fractions and from measurements of polyamine binding to the protein. These results indicate that the spermidine and putrescine transport system can be defined as a bacterial periplasmic transport system. PMID- 1939143 TI - Purification and interaction properties of the human RNA polymerase B(II) general transcription factor BTF2. AB - A general transcription factor (BTF2) has been purified from HeLa whole cell extract and shown to be absolutely required for the formation of a functional initiation complex. We also demonstrate that this factor binds in solution to RNA polymerase B(II) and to the other general transcription factors BTF1(TFIID), BTF3, and BTF4. These results strongly suggest the existence of multiple interactions between the various components of the multiprotein initiation complex. PMID- 1939144 TI - Site-directed mutagenesis studies on the recombinant thioesterase domain of chicken fatty acid synthase expressed in Escherichia coli. AB - The animal fatty acid synthase is a multifunctional protein with a subunit molecular weight of 260,000. We recently reported the expression and characterization of the acyl carrier protein and thioesterase domains of the chicken liver fatty acid synthase in Escherichia coli. In order to gain insight into the mechanism of action of the thioesterase domain, we have replaced the putative active site serine 101 with alanine and cysteine and the conserved histidine 274 with alanine by site-directed mutagenesis. While both the Ser101--- Ala and His274----Ala mutant proteins were inactive, the Ser101----Cys mutant enzyme (thiol-thioesterase) retained considerable activity, but the properties of the enzyme were changed from an active serine esterase to an active cysteine esterase, providing strong evidence for the role of Ser101 as the active site nucleophile. In order to further probe into the role of His274, a double mutant was constructed containing both the Ser101----Cys and the His274----Ala mutations. The double-mutant protein was inactive and exhibited diminished reactivity of the Cys-SH to iodoacetamide as compared to that of the Ser101--- Cys-thioesterase, suggesting a role of His274 as a general base in withdrawing the proton from the Cys-SH in the thiol-thioesterase or Ser101 in the wild-type enzyme. Incubation of the recombinant thioesterases with [1-14C] palmitoyl-CoA resulted in the incorporation of [1-14C] palmitoyl into the enzyme only in the double mutant, suggesting that Cys-SH of the double mutant is reactive enough to form the palmitoyl-S-enzyme intermediate. This intermediate is not hydrolyzed because of the lack of His274, which is required for the attack of H2O on the acyl enzyme. These results suggest that the catalytic mechanism of the thioesterases may be similar to that of the serine proteases and lipases, which employ a serine-histidine-aspartic acid catalytic triad as part of their catalytic mechanism. PMID- 1939145 TI - UDP-rhamnose:flavanone-7-O-glucoside-2''-O-rhamnosyltransferase. Purification and characterization of an enzyme catalyzing the production of bitter compounds in citrus. AB - The rhamnosyltransferase catalyzing the production of the bitter flavanone glucosides, naringin and neohesperidin, was purified to homogeneity. The enzyme catalyzes the transfer of rhamnose from UDP-rhamnose to the C-2 hydroxyl group of glucose attached via C-7-O- of naringenin or hesperetin. To our knowledge this is the first complete purification of a rhamnosyl-transferase. The enzyme from young pummelo leaves was purified greater than 2,700-fold to a specific activity of over 600 pmol/min/mg of protein by sequential column chromatographies on Sephacryl S-200, reactive green 19-agarose, and Mono-Q. The enzyme was selectively eluted from the green dye column with only three other proteins by a pulse of the substrate hesperetin-7-O-glucoside followed by UDP. The rhamnosyltransferase is monomeric (approximately 52 kDa) by gel filtration and electrophoresis. The enzyme rhamnosylates only with UDP-rhamnose. Flavonoid-7-O glucosides are usable acceptors but 5-O-glucosides or aglycones are not. It is inhibited by 10 microM UDP, its end product, but not by naringin or neohesperidin. Several flavonoid-aglycones at 100 microM inhibited the rhamnosyltransferase; UDP-sugars did not. The Km for UDP-rhamnose was similar with prunin (1.3 microM) and hesperetin-7-O-glucoside (1.1 microM) as substrate. The affinity for the natural acceptor prunin (Km = 2.4 microM) was much higher than for hesperetin-7-O-glucoside (Km = 41.5 microM). The isolation of the gene may enable its use in genetic engineering directed to modifying grapefruit bitterness. PMID- 1939146 TI - Protection from tumor necrosis factor-mediated cytolysis by overexpression of plasminogen activator inhibitor type-2. AB - Pretreatment of HT-1080 fibrosarcoma cells with tumor necrosis factor (TNF) induced resistance to the cytolytic activity of this cytokine in combination with cycloheximide. This resistance correlated with the synthesis of plasminogen activator inhibitor type-2 (PAI-2). HT-1080 cells were transfected with a PAI-2 expression vector in both sense and antisense orientation. The resistance to TNF mediated cytolysis of transfected cell clones was correlated with the level of PAI-2 expression. Cells expressing antisense PAI-2 RNA showed reduced expression of PAI-2 and increased sensitivity to TNF-mediated cytolysis. Cells expressing constitutively PAI-2 were treated with TNF and cycloheximide to select cells with increased resistance to cytolysis and enhanced PAI-2 expression. PAI-2 gradually disappeared during a treatment with TNF and cycloheximide. This finding suggested that PAI-2 formed a complex with a target proteinase, which could be involved in mediating the cytolytic activity of TNF. PMID- 1939148 TI - 19F NMR quantitation of lens aldose reductase activity using 3-deoxy-3-fluoro-D glucose. AB - In the present study we have determined the kinetics of 3-deoxy-3-fluoro-D glucose (3-FG) as a substrate for the aldose reductase reaction in vitro. In addition, we compared the 3-deoxy-3-fluoro-sorbitol (3-FS) production rates from 3-FG in the intact lens using 19F NMR with conventional aldose reductase determinations in extracts from the same lenses. The affinity of in vitro aldose reductase for 3-FG was approximately 20 times greater (9.3 mM) than that for glucose (188 mM). An excellent correlation between the rate of 3-FS production in the intact canine lens, determined with 19F NMR, and extracted aldose reductase activity was observed. The relatively high affinity of aldose reductase for 3-FG and the correlation of 3-FS production with enzyme activity in the intact lens suggests that 3-FS production from 3-FG detected by 19F NMR could provide an accurate noninvasive determination of aldose reductase activity in the eye lens. PMID- 1939147 TI - Expression of truncated forms of the bovine growth hormone gene in cultured mouse cells. AB - A synthetic oligonucleotide, 5'-d(CTAGT-CTAGACTAG)-3' which encodes translational termination codons in three reading frames, was inserted into either exon IV (pbGH-4A) or V (pbGH-5A) of the bovine growth hormone gene. The resultant plasmids, under the transcriptional regulation of the mouse metallothionein 1 promoter, were introduced into cultured mouse L-cells or rat GH3 cells. Compared to wild type bGH RNA, bGH-specific RNA transiently expressed from pBGH-5A or pBGH 4A DNA in mouse L-cells was similar or slightly smaller in size, respectively. Unexpectedly, bGH-4A RNA lacked exon IV sequences. Immunofluorescence and immunoprecipitation analyses revealed that wild type bGH was localized to the Golgi apparatus, while truncated hormones were confined to the cytoplasmic compartment of transfected cells. In addition, truncated hormones were shown to be secretion-defective albeit the bGH signal peptide was efficiently and precisely processed. Thus, structural alterations in the bGH gene can dramatically affect bGH precursor mRNA processing and hormone localization within cultured mouse fibroblast or rat pituitary cells. PMID- 1939149 TI - Regulated expression of p18, a major phosphoprotein of leukemic cells. AB - p18 is a phosphoprotein that is present in great abundance in acute leukemia blasts and in less abundance in proliferating lymphocytes. This protein undergoes major changes in its state of phosphorylation upon induction of differentiation of leukemic cells in culture. The same protein appears to be involved in a variety of other cellular processes that include regulation of hormone secretion, T cell activation, muscle differentiation, and brain development. In this report, we describe our studies of the regulation of expression of this gene in leukemic cells. We show that the expression of this gene is markedly reduced upon induction of differentiation of a variety of leukemic cells in culture. We use a cDNA clone that we constructed earlier which encodes this protein as a probe to isolate the human chromosomal p18 gene. We characterize the 5' end of this gene in detail and identify its promoter element. We also identify a regulatory element in the first intervening sequence (IVS-1) of this gene which loses its DNase I hypersensitivity upon induction of differentiation of leukemic cells in culture. Our DNase I footprinting experiments demonstrate nuclear protein binding to multiple sequence motifs within its promoter element and its IVS-1 regulatory element. Functional studies using a transient expression system show that deletion of these sequence motifs has profound effects on the expression of this gene. These studies begin to shed some light on the mechanism of regulation of a gene that may be involved in control of cell growth and differentiation and in a variety of other vital cellular processes. PMID- 1939150 TI - Conversion of the Alzheimer's beta-amyloid precursor protein (APP) Kunitz domain into a potent human neutrophil elastase inhibitor. AB - Site-specific mutagenesis techniques have been used to construct active site variants of the Kunitz-type protease inhibitor domain present in the Alzheimer's beta-amyloid precursor protein (APP-KD). Striking alteration of its protease inhibitory properties were obtained when the putative P1 residue, arginine, was replaced with the small hydrophobic residue valine. The altered protein was no longer inhibitory toward bovine pancreatic trypsin, human Factor XIa, mouse epidermal growth factor-binding protein, or bovine chymotrypsin, all of which are strongly inhibited by the unaltered APP-KD (Sinha, S., Dovey, H. F., Seubert, P., Ward, P. J., Blacher, R. W., Blaber, M., Bradshaw, R. A., Arici, M., Mobley, W. C., and Lieberburg, I. (1990) J. Biol. Chem. 265, 8983-8985). Instead, the P1-Val APP-KD was a potent inhibitor of human neutrophil elastase, with a Ki = 0.8 nM, as estimated by the inhibition of the activity of human neutrophil elastase measured using a chromogenic substrate. It also inhibited the degradation of insoluble elastin by the enzyme virtually stoichiometrically. Replacement of the P1' (Ala) and P2' (Met) residues of P1-Val-MKD with the corresponding residues (Ser, Ile) from alpha 1-proteinase inhibitor resulted in an inactive protein, underscoring the mechanistic differences between the serpins from the Kunitz-type protease inhibitor family. These results confirm the importance of the P1 arginine residue of APP-KD in determining inhibitory specificity, and are also the first time that a single amino acid replacement has been shown to generate a specific potent human neutrophil elastase inhibitor from a human KD sequence. PMID- 1939152 TI - The use of chemical nucleases to analyze RNA-protein interactions. The TFIIIA-5 S rRNA complex. AB - The complex of Xenopus transcription factor IIIA (TFIIIA) with 5 S rRNA was analyzed in nuclease protection experiments using hydroxyl radical. The protection pattern reveals that TFIIIA interacts with a substantial amount of the RNA molecule, with close association between the factor and the arm of the RNA composed of helix IV-loop E-helix V. Additional sites of protection punctuate the other arm of the molecule. Important contact sites within the complex were identified in "missing nucleoside" experiments. Random single-nucleoside gaps were introduced into 5 S rRNA using either Fe[EDTA]2-/H2O2 or bis(1,10 phenanthroline)copper(I). This modified RNA was allowed to bind to TFIIIA in an exchange reaction, and, afterward, bound and unbound fractions were separated on nondenaturing polyacrylamide gels. Missing nucleoside positions specifically enriched in the unbound fraction of RNA are located in the two strands that comprise loop E. These are not necessarily sites of sequence-specific contacts, but rather may constitute a region of secondary structure essential to recognition and binding of TFIIIA to 5 S rRNA. PMID- 1939151 TI - Des-Arg9 bradykinin modulates DNA synthesis, phospholipase C, and protein kinase C in cultured mesangial cells. Distinction from effects of bradykinin. AB - The effects of the neuropeptide bradykinin (BK) and its natural proteolytic fragment Des-Arg9 bradykinin (DBK) on DNA synthesis and phospholipase C activation were investigated in cultured mesangial cells. DBK, acting through a distinct bradykinin receptor, induced DNA synthesis in serum-starved cultured mesangial cells. The effect of DBK was dose dependent (ED50 = 0.6 microM) and was strongly potentiated by insulin. Under the same conditions, BK had no effect. Down-regulation of protein kinase C by long term pretreatment with 12-O tetradecanoylphorbol-13-acetate (TPA) markedly reduced DBK-induced DNA synthesis. In the same way, co-incubation with the protein kinase C inhibitor staurosporine potently attenuated the response to DBK, suggesting a role of protein kinase C in DBK-induced mitogenesis. Analysis of phosphoproteins from 32P-labeled mesangial cells by two-dimensional gel electrophoresis revealed that DBK, like TPA but not BK, induced a net increase in the phosphorylation of an acidic cellular protein migrating with an apparent Mr = 80,000 (termed 80K), identified as a major and specific substrate of protein kinase C. Phosphorylation of the 80K protein by DBK or TPA was completely abolished in cells depleted of protein kinase C. DBK and TPA also induced an increase in phosphorylation of an Mr = 28,000 protein. Moreover, DBK but not TPA stimulated the phosphorylation of an Mr = 18,000 protein in normal as well as in protein kinase C-depleted cells. Analysis of phospholipase C activation revealed that DBK induced a large and sustained increase in diacylglycerol production and inositol phosphate accumulation over a 10-min incubation. BK had only a minor effect on both parameters. These results demonstrate that DBK, but not BK, modulates DNA synthesis through protein kinase C activation in cultured mesangial cells. PMID- 1939153 TI - Kinetic analysis of the inhibition of the epidermal growth factor receptor tyrosine kinase by Lavendustin-A and its analogue. AB - Lavendustin-A was reported to be a potent tyrosine kinase inhibitor of the epidermal growth factor (EGF) receptor (Onoda, T., Iinuma, H., Sasaki, Y., Hamada, M., Isshibi, K., Naganawa, H., Takeuchi, T., Tatsuta, K., and Umezawa, K. (1989) J. Nat. Prod. 52, 1252-1257). Its inhibition kinetics was studied in detail using the baculovirus-expressed recombinant intracellular domain of the EGF receptor (EGFR-IC). Lavendustin-A (RG 14355) is a slow and tight binding inhibitor of the receptor tyrosine kinase. The pre-steady state kinetic analysis demonstrates that the inhibition corresponds to a two-step mechanism in which an initial enzyme-inhibitor complex (EI) is rapidly formed followed by a slow isomerization step to form a tight complex (EI*). The dissociation constant for the initial rapid forming complex is 370 nM, whereas the overall dissociation constant is estimated to be less than or equal to 1 nM. The difference between the two values is due to the tight binding nature of the inhibitor to the enzyme in EI*. The kinetic analysis using a preincubation protocol to pre-equilibrate the enzyme with the inhibitor in the presence of one substrate showed that Lavendustin-A is a hyperbolic mixed-type inhibitor with respect to both ATP and the peptide substrate, with a major effect on the binding affinities for both substrates. An analogue of Lavendustin-A (RG 14467) showed similar inhibition kinetics to that of Lavendustin-A. The results of the pre-steady state analysis are also consistent with the proposed two-step mechanism. The dissociation constant for the initial fast forming complex in this case is 3.4 microM, whereas the overall dissociation constant is estimated to be less than or equal to 30 nM. It is a partial (hyperbolic) competitive inhibitor with respect to ATP. Its inhibition is reduced to different extents by different peptide substrates, when the peptide is added to the enzyme simultaneously with the inhibitor. When studied with the least protective peptide, K1 (a peptide containing the major autophosphorylation site of the EGF receptor), RG 14467 acts as a hyperbolic noncompetitive inhibitor with respect to the peptide. PMID- 1939154 TI - Cytotoxic properties of DAB486EGF and DAB389EGF, epidermal growth factor (EGF) receptor-targeted fusion toxins. AB - Elevated expression of the receptor for epidermal growth factor (EGF) is a characteristic of several malignancies including those of the breast, bladder, prostate, lung, and neuroglia. To therapeutically target the cytotoxic action of diphtheria toxin to EGF receptor-expressing tumor cells, we have constructed a hybrid gene in which the sequences for the binding domain of diphtheria toxin have been replaced by those for human EGF. The resulting fusion toxins, DAB486EGF and DAB389EGF, bind specifically to the EGF receptor and inhibit protein synthesis in a variety of EGF receptor expressing human tumor cell lines with an IC50 as low as 0.1 pM. Comparisons of DAB486EGF and DAB389EGF showed that DAB389EGF was consistently 10- to 100-fold more cytotoxic than DAB486EGF. Like diphtheria toxin, the cytotoxic action of DAB389EGF results from ADP-ribosylation of elongation factor-2 and is sensitive to the action of chloroquine. Studies of the kinetics of cellular intoxication showed that a 15-min exposure of EGF receptor-expressing A431 cells to DAB389EGF results in complete protein synthesis inhibition within 4 h. Furthermore, inhibition of protein synthesis results in elimination of human tumor cell colonies. These findings show that DAB389EGF is a potential therapeutic agent for a wide variety of EGF receptor-expressing solid tumors. PMID- 1939155 TI - Turnover of the transferrin receptor is not influenced by removing most of the extracellular domain. AB - We treated intact cells with trypsin to remove most of the external domain of the transferrin receptor and investigated what effect the absence of the external domain had on the turnover of the fragment that remained associated with the cells. To detect the cell-associated tryptic fragment, which contains a small amount of the external domain, the transmembrane domain, and the cytoplasmic domain, we prepared an anti-peptide antibody against a segment of the cytoplasmic domain. This antibody specifically immunoprecipitated the intact transferrin receptor as well as a 21-kDa peptide from trypsin-treated HeLa cells. Several lines of evidence indicated that the 21-kDa peptide was the cell-associated tryptic fragment of the transferrin receptor. The fragment was only present in trypsin-treated cells; the fragment migrated as a dimer in nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, as it should if it were derived from the transferrin receptor; a goat antibody prepared to the purified human transferrin receptor also precipitated the 21-kDa peptide from trypsinized cells. In addition, treating the tryptic fragment with neuraminidase increased the electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels, suggesting the fragment contained O-linked carbohydrate. When cells were trypsinized and then incubated at 37 degrees C, the half-life of the tryptic fragment (15 +/- 4 h) was not significantly different than the half-life of the intact receptor (19 +/- 6 h). This indicates that removing 95% of the external domain of the transferrin receptor has little effect on processes operating in the turnover of the receptor. PMID- 1939156 TI - Metabolic derepression of alpha-amylase gene expression in suspension-cultured cells of rice. AB - We present evidence to show that the alpha-amylase gene family in rice is under two different modes of regulation: 1) hormonal regulation in germinating seeds, and 2) metabolic repression in cultured cells by available carbohydrate nutrients. Expression of alpha-amylase genes in deembryoed rice seeds is known to be induced by exogenous gibberellic acid. On the other hand, expression of alpha amylase genes in suspension-cultured cells is induced by the deprivation of carbohydrate nutrient. A lag period of 2-4 h is required for the induction of alpha-amylase mRNA in sucrose-depleted medium. The induction of alpha-amylase expression is extraordinarily high and levels of alpha-amylase mRNA can be increased 8-20-folds after 24 h of sucrose starvation. The synthesis and secretion of alpha-amylase is also dependent upon the level of carbon source. The derepression or repression of alpha-amylase synthesis can be readily reversed by the deprivation or replenishment of sucrose in the medium, respectively. Glucose and fructose exert a repression on the alpha-amylase synthesis similar to that of sucrose. A hypothesis that explains the induction of alpha-amylase synthesis by carbohydrate starvation is proposed. Our data have suggested a hitherto undiscovered, potentially important control mechanism of carbohydrate metabolism in higher plants. PMID- 1939157 TI - Carboxyl-terminal proteolytic processing of matrix Gla protein. AB - The present study was undertaken to determine the extent of COOH-terminal proteolytic processing in matrix Gla protein (MGP), a 10-kDa protein which contains 5 residues of the vitamin K-dependent Ca2+ binding amino acid, gamma carboxyglutamic acid (Gla). Two forms of MGP were isolated from demineralization and urea extracts of bovine cortical bone, one 79 residues in length with the COOH terminus Phe-Arg-Gln and the other 83 residues in length with the COOH terminus Phe-Arg-Gln-Arg-Arg-Gly-Ala. The 84-residue form of bovine MGP predicted from the message structure could not be detected in the bone extracellular matrix extracts, and it therefore seems probable that the lysine at position 84 was removed by the action of a carboxypeptidase B-like enzyme prior to secretion. A plausible sequence of proteolytic cleavages that could generate the 79-residue form of MGP would be a trypsin-like cleavage at Arg80-Arg81 or Arg81-Gly82 followed by carboxypeptidase B-like cleavage to remove COOH-terminal arginine(s). Since essentially equal amounts of the 79- and 83-residue forms of MGP were also detected in bovine articular cartilage and plasma, it seems likely that the COOH terminal processing events identified in bone apply to many of the other tissues which synthesize this protein. Only one form of MGP was detected in human bone extracts, a 77-residue protein that lacks the COOH-terminal residues Arg-Lys-Arg Arg-Gly-Thr-Lys. This shortened version of human MGP is consistent with the proposed model for COOH-terminal processing, since the amino acid substitution in the COOH terminus of the human protein, Lys79 for Gln79, would allow removal of the additional basic residues from the human MGP COOH terminus by the action of the carboxypeptidase B-like enzymic activity. Recent studies have shown that MGP is strongly induced by retinoic acid in fibroblasts, chondrocytes, and osteoblasts, a response which suggests that MGP mediates an action of retinoic acid on an aspect of cell growth or differentiation. If this hypothesis is true, the present evidence for complex COOH-terminal processing events could provide a means to regulate the as yet unknown activity of MGP in the extracellular environment in a mechanism similar to the activation of hormones such as anaphlotoxins and kinins. PMID- 1939158 TI - Characterization of progesterone receptor binding to the 90- and 70-kDa heat shock proteins. AB - In this study a model system for expression of the chicken progesterone receptor in cultured cells was developed using a quail fibroblast cell line, QT6. The chicken progesterone receptor form A expressed in QT6 cells was evaluated and determined to have a number of similarities to receptor isolated from chicken oviduct. These include hormone binding, sedimentation profile, phosphorylation pattern, heat shock protein (hsp) 70 and hsp90 associations and the ability to stimulate a reporter gene construct. Therefore, the receptor expressed in this system functioned adequately for further evaluation of the particular region (or regions) involved in hsp70 and hsp90 binding. Several receptor deletion mutants were tested for hsp70/hsp90 binding; only the d369-659 mutant, which has the entire steroid-binding domain deleted, was unable to bind hsp90 and hsp70. Three separate regions of the steroid-binding domain were found to partially restore hsp90 and hsp70 binding to the d369-659 mutant protein. However, hsp binding was not abolished when these or other regions of the steroid binding domain were deleted individually. These findings indicate that hsp90 and hsp70 both bind to the steroid-binding domain of the receptor through interactions at multiple locations or through some structural quality that is distributed throughout this region of the protein. PMID- 1939159 TI - Mutation of a single amino acid converts germ cell alkaline phosphatase to placental alkaline phosphatase. AB - Human placental and germ cell alkaline phosphatases (PLAP and GCAP, respectively), are characterized by their differential sensitivities to inhibition by L-leucine, EDTA, and heat. Yet, they differ by only 7 amino acids at positions 15, 67, 68, 84, 241, 254, and 429 within their respective 484 residues. To determine the structural basis and the amino acid(s) involved in these physicochemical differences, we constructed three GCAP mutants by site directed mutagenesis and six GCAP/PLAP chimeras and then expressed these alkaline phosphatase mutants in COS-1 cells. We report that the differential reactivity of PLAP and GCAP depends critically on a single amino acid at position 429. GCAP with Gly-429 is strongly inhibited by L-leucine, EDTA, and heat, whereas PLAP with Glu-429 is resistant. By substituting Gly-429 of GCAP with a series of amino acids, we demonstrate that the relative sensitivities of these mutants to L leucine, EDTA, and heat inhibition are, in general, parallel. Mutants in the order of resistance to these treatments are: Glu (most resistant), Asp/Ile/Leu, Gln/Val/Lys, Ser/His, and Arg/Thr/Met/Cys/Phe/Trp/Tyr/Pro/Asn/Ala/Gly (least resistant). However, the Ser-429 and His-429 mutants were more resistant to EDTA and heat inhibition than the wild-type GCAP, but were equally sensitive to L leucine inhibition. Structural analysis of mammalian alkaline phosphatase modeled on the refined crystal structure of Escherichia coli alkaline phosphatase indicates that the negative charge of Glu-429 of PLAP, which simultaneously stabilizes the protein as a whole and the metal binding specifically, probably acts through interactions with the metal ligand His-320 (His-331 in E. coli alkaline phosphatase). Replacement of codon 429 with Gly in GCAP leads to destabilization and loosening of the metal binding. The data suggest that the natural binding site for L-leucine may be near position 429, with the amino and carboxyl groups of L-leucine interacting with bound phosphate and His-432 (His 412 in E. coli alkaline phosphatase), respectively. PMID- 1939161 TI - Protein synthesis inhibition stabilizes urokinase-type plasminogen activator mRNA. Studies in vivo and in cell-free decay reactions. AB - Inhibition of protein synthesis stabilizes a number of mRNAs, but little is known about the mechanism. To understand the relationship between protein synthesis and mRNA stability, we studied the degradation of calcitonin-induced urokinase-type plasminogen activator (uPA) mRNA in LLC-PK cells. uPA mRNA became highly stable by pretreatment with either cycloheximide or pactamycin, and the stabilizing effect of cycloheximide treatment was time dependent with the full effect exerted by 60 min. Stabilization was also observed with histone H4 mRNA but only partially with c-myc mRNA. To further analyze, we developed a cell-free decay reaction system based on post-mitochondrial supernatant (PMS). In this system, uPA mRNA was completely stable when fractions were obtained from cells pretreated with cycloheximide, but very unstable in control fractions, paralleling uPA mRNA stability in intact cells. However, in contrast to uPA mRNA and the in vivo observation, histone H4 mRNA was unstable whether or not the cells were pretreated with cycloheximide. These results suggest that inhibition of protein synthesis stabilizes mRNAs in at least two different ways in LLC-PK1 cells. When PMS from cycloheximide/calcitonin-treated cells was mixed with PMS from untreated cells, uPA mRNA was not destabilized. This suggests that a putative labile factor responsible for uPA mRNA degradation is not a soluble protein. PMID- 1939160 TI - Insulin-induced p21ras activation does not require protein kinase C, but a protein sensitive to phenylarsine oxide. AB - Insulin treatment of fibroblasts overexpressing the insulin receptor causes a rapid accumulation of the GTP-bound form of p21ras. We have studied the involvement of protein kinase C (PKC) in, and the effect of phenylarsine oxide (PAO), a putative inhibitor of tyrosine phosphatase activity on, this process. Activation of p21ras was not observed when the cells were stimulated with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and pretreatment with TPA for 16 h, sufficient to down-regulate PKC activity, did not abolish p21ras activation by insulin. These results show that PKC is not involved in the insulin induced activation of p21ras. Pretreatment of the cells with PAO for 5 min completely blocked insulin-induced p21ras activation. Addition of 2,3 dimercaptopropanol prevented this inhibition by PAO. Also, addition of PAO after insulin stimulation could reverse the activation of p21ras. Since PAO did not affect overall phosphorylation of the insulin receptor beta-chain, we conclude that a PAO-sensitive protein is involved in the induction of p21ras activation by insulin. PMID- 1939162 TI - Cytotoxic potential of ribonuclease and ribonuclease hybrid proteins. AB - Pancreatic RNase injected into Xenopus oocytes abolishes protein synthesis at concentrations comparable to the toxin ricin yet has no effect on oocyte protein synthesis when added to the extracellular medium. Therefore RNase behaves like a potent toxin when directed into a cell. To explore the cytotoxic potential of RNase toward mammalian cells, bovine pancreatic ribonuclease A was coupled via a disulfide bond to human transferrin or antibodies to the transferrin receptor. The RNase hybrid proteins were cytotoxic to K562 human erythroleukemia cells in vitro with an IC50 around 10(-7) M whereas greater than 10(-5) M native RNase was required to inhibit protein synthesis. Cytotoxicity requires both components of the conjugate since excess transferrin or ribonuclease inhibitors added to the medium protected the cells from the transferrin-RNase toxicity. Compounds that interfere with transferrin receptor cycling and compartmentalization such as ammonium chloride decreased the cytotoxicity of transferrin-RNase. After a dose dependent lag period inactivation of protein synthesis by transferrin-RNase followed a first-order decay constant. In a clonogenic assay that measures the extent of cell death 1 x 10(-6) M transferrin-RNase killed at least 4 logs or 99.99% of the cells whereas 70 x 10(-6) M RNase was nontoxic. These results show that RNase coupled to a ligand can be cytotoxic. Human ribonucleases coupled to antibodies also may exhibit receptor-mediated toxicities providing a new approach to selective cell killing possibly with less systemic toxicity and importantly less immunogenicity than the currently employed ligand-toxin conjugates. PMID- 1939163 TI - Comparison of RNases and toxins upon injection into Xenopus oocytes. AB - Several toxins abolish cellular protein synthesis by attacking specific sites in 28 S RNA. One of these toxins, alpha-sarcin, is an RNase that also cleaves nonspecifically on the 3' side of purines in deproteinized RNA. Several other RNases were injected into Xenopus oocytes, examined for their ability to abolish protein synthesis, and compared with alpha-sarcin and ricin. Surprisingly, pancreatic RNase A or B abolished oocyte protein synthesis at concentrations (approximately 0.03 nM) comparable to, or lower than, the amount of alpha-sarcin (approximately 2 nM) or ricin (approximately 0.07 nM) required to abolish protein synthesis. RNases S and T1 only inhibited oocyte protein synthesis when used at concentrations approximately 10 x higher than RNase A whereas RNases C, T2, U2, and nuclease P1 required concentrations approximately 100 times higher than RNase A to abolish protein synthesis. There was a direct correlation between the degradation of oocyte RNA and the inhibition of protein synthesis. The RNase inhibitors RNasin and Inhibit-Ace injected into the oocyte both prevented RNase A from hydrolyzing oocyte rRNA and abolishing protein synthesis. Enzymatically inactive oxidized RNase A did not inhibit protein synthesis when injected into the oocyte. None of the RNases or alpha-sarcin abolished protein synthesis when added to oocyte extracellular medium. Angiogenin is a human plasma protein that induces blood vessel formation in chick embryos, has 35% amino acid identity with RNase A, and cleaves 18 S and 28 S RNA in rabbit reticulocyte lysates (St. Clair, D. K., Rybak, S. M., Riordan, J. F. & Vallee, B. L. (1988) Biochemistry 27, 7263 7268, and references therein). Recombinant angiogenin injected into oocytes abolished protein synthesis, and this toxic effect was inhibited by RNasin but was not inhibited by Inhibit-Ace. Unlike RNase A and the other nucleases that hydrolyzed cellular rRNA, no cleavage of 18 or 28 S RNA by recombinant angiogenin was seen at concentrations 100 x greater than necessary to abolish protein synthesis. Recombinant angiogenin must selectively attack specific RNA(s) or another target in the cell. PMID- 1939164 TI - Pancreatic beta cells express two autoantigenic forms of glutamic acid decarboxylase, a 65-kDa hydrophilic form and a 64-kDa amphiphilic form which can be both membrane-bound and soluble. AB - The 64-kDa pancreatic beta-cell autoantigen, which is a target of autoantibodies associated with early as well as progressive stages of beta-cell destruction, resulting in insulin-dependent diabetes (IDDM) in humans, has been identified as the gamma-aminobutyric acid-synthesizing enzyme glutamic acid decarboxylase. We have identified two autoantigenic forms of this protein in rat pancreatic beta cells, a Mr 65,000 (GAD65) hydrophilic and soluble form of pI 6.9-7.1 and a Mr 64,000 (GAD64) component of pI 6.7. GAD64 is more abundant than GAD65 and has three distinct forms with regard to cellular compartment and hydrophobicity. A major portion of GAD64 is hydrophobic and firmly membrane-anchored and can only be released from membrane fractions by detergent. A second portion is hydrophobic but soluble or of a low membrane avidity, and a third minor portion is soluble and hydrophilic. All the GAD64 forms have identical pI and mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Results of pulse-chase labeling with [35S]methionine are consistent with GAD64 being synthesized as a soluble protein that is processed into a firmly membrane-anchored form in a process which involves increases in hydrophobicity but no detectable changes in size or charge. All the GAD64 forms can be resolved into two isoforms, alpha and beta, which differ by approximately 1 kDa in mobility on sodium dodecyl sulfate polyacrylamide gel electrophoresis but are identical with regard to all other parameters analyzed in this study. GAD65 has a shorter half-life than the GAD64 forms, remains hydrophilic and soluble, and does not resolve into isomers. Comparative analysis of the brain and beta-cell forms of GAD show that GAD65 and GAD64 in pancreatic beta-cells correspond to the larger and smaller forms of GAD in brain, respectively. The expression of different forms and the flexibility in subcellular localization of the GAD autoantigen in beta-cells may have implications for both its function and autoantigenicity. PMID- 1939165 TI - The PQ/PQH2 ratio and occupancy of photosystem II-QB site by plastoquinone control the degradation of D1 protein during photoinhibition in vivo. AB - Photoinactivation of photosystem II (PSII) and light-dependent degradation of the reaction center II (RCII) protein D1 have been investigated in Chlamydomonas reinhardtii mutants D6, AC208, and B4 deficient in cytochrome b6/f, plastocyanin, and photosystem I (PSI) activity, respectively. These mutants possess active PSII and reduce plastoquinone (PQ) but cannot oxidize plastoquinol (PQH2) via light dependent reduction of NADP. In light-exposed cells a high ratio PQH2/PQ and a low turnover of PQ/PQH2 at the RCII-QB site are maintained. In all mutants photoinactivation of RCII was slower as compared to the wild-type (wt) cells, and D1 degradation was drastically decreased. The degradation of D1 was also lower in the wt cells under anaerobic conditions and presence of ascorbate, while raising the concentration of dissolved oxygen increased the degradation of the D1 protein in the AC208 mutant. Photoinactivation and light-dependent degradation of the D1 protein were drastically increased in the Scenedesmus obliquus LF-1 mutant cells altered in its PSII manganese binding and thus unable to reduce PQ using water as an electron donor. Diuron inhibited the light-dependent degradation of D1 protein in both the LF-1 mutant and wt cells. Based on these results we propose that availability of PQ at the QB site is required for (i) the photoinactivation process of the RCII acceptor side followed by inactivation of the donor side leading to the generation of harmful cation radicals (Z+, P680+, chlz+) which damage the D1 protein, and (ii) the accessibility of the cleavage site of the damaged D1 protein to proteolytic degradation. PMID- 1939166 TI - Retinoic acid induces the expression of alkaline phosphatase in P19 teratocarcinoma cells. AB - Retinoic acid (RA), the natural acid derivative of vitamin A, can induce the differentiation of some cell lines, such as the murine P19 teratocarcinoma cell line. RA can alter the expression of specific genes and the level of the corresponding protein. This report describes the effect of RA on the level of the alkaline phosphatase (ALP) mRNA and protein in P19 teratocarcinoma cells. RA caused a rapid, dose-dependent, and protein synthesis-dependent induction of ALP activity. The increased enzyme activity was detected 4 h after initiation of treatment and maximum induction of ALP activity required 48 h of RA exposure. Increased enzymatic activity was coincidental with increased levels of both a 67 kDa ALP protein and ALP mRNA. By Northern (RNA) blot analysis the increase of a 2.7-kilobase ALP mRNA was observed within 3 h of RA treatment. The RA-induced enhanced ALP mRNA level did not appear to be mainly due to the stabilization of preexisting mRNA, but rather to an increase in transcription of the ALP gene. PMID- 1939167 TI - xP1 and xP4. P-domain peptides expressed in Xenopus laevis stomach mucosa. AB - Two different precursors for secretory polypeptides from the stomach of Xenopus laevis have been characterized by cDNA cloning. Both mature polypeptides are potential candidates for gastrointestinal growth factors. One, xP1, is the X. laevis homologue of the pS2 gene product consisting only of a single P-domain, whereas the second, xP4, is a novel polypeptide formed by four P-domains arranged in tandem. Northern analysis detected both transcripts in the stomach but not in the skin or the brain. In situ hybridizations localized the expression of both precursors in surface mucous cells of the gastric mucosa. With an antibody generated against the deduced C-terminal end of xP4, the mature polypeptide was investigated by Western analysis revealing N-glycosylation of xP4. PMID- 1939168 TI - Lysosomal membrane glycoproteins. Structure, biosynthesis, and intracellular trafficking. PMID- 1939169 TI - Expression of the human beta-amyloid protein of Alzheimer's disease specifically in the brains of transgenic mice. AB - The human beta-amyloid protein is deposited in senile plaques and in the cerebro vasculature of people with Alzheimer's disease and Down's syndrome. The precise role of beta-amyloid in Alzheimer's disease pathology is presently unknown. To study the properties of beta-amyloid in vivo, we generated transgenic mice that harbor the gene for the carboxyl-terminal 100 amino acids of the human amyloid precursor protein, beginning with the beta-amyloid region, under control of the JC viral early region promoter. The mRNA is expressed exclusively in brain tissue. Further, we demonstrate increased levels of beta-amyloid immunoreactivity on fixed brain tissue. These animals will be useful as a model to study beta amyloid deposition and its consequences. PMID- 1939170 TI - Isolation and characterization of a Saccharomyces cerevisiae mutant disrupted for the succinate dehydrogenase flavoprotein subunit. AB - A partial genomic clone of the flavoprotein subunit of the mitochondrial enzyme, succinate dehydrogenase (EC 1.3.99.1) from Saccharomyces cerevisiae has been isolated. The partial clone was used to construct, by targeted gene disruption, a yeast mutant with a defective flavoprotein subunit gene. Submitochondrial membranes from the mutant are defective in activities requiring a functional succinate dehydrogenase but not in other respiratory chain activities. In addition, the mutant contains significantly lower levels of covalently attached flavin adenine dinucleotide cofactor than does the wild type. Disruption of the flavoprotein subunit gene results in the simultaneous loss of both the iron sulfur and the flavoprotein subunits from mitochondrial membranes. PMID- 1939171 TI - Structure of a recombinant calmodulin from Drosophila melanogaster refined at 2.2 A resolution. AB - The crystal structure of calmodulin (Mr 16,700, 148 residues) from Drosophila melanogaster as expressed in a bacterial system has been determined and refined at 2.2-A resolution. Starting with the structure of mammalian calmodulin, we produced an extensively refitted and refined model with a conventional crystallographic R value of 0.197 for the 5,239 reflections (F greater than or equal to 2 sigma (F)) within the 10.0-2.2-A resolution range. The model includes 1,164 protein atoms, 4 calcium ions, and 78 water molecules and has root mean square deviations from standard values of 0.018 A for bond lengths and 0.043 A for angle distances. The overall structure is similar to mammalian calmodulin, with a seven-turn central helix connecting the two calcium-binding domains. The "dumb-bell" shaped molecule contains seven alpha-helices and four "EF hand" calcium-binding sites. Although the amino acid sequences of mammalian and Drosophila calmodulins differ by only three conservative amino acid changes, the refined model reveals a number of significant differences between the two structures. Superimposition of the structures yields a root mean square deviation of 1.22 A for the 1,120 equivalent atoms. The calcium-binding domains have a root mean square deviation of 0.85 A for the 353 equivalent atoms. There are also differences in the amino terminus, the bend of the central alpha-helix, and the orientations of some of the side chains. PMID- 1939174 TI - Alcohol dehydrogenase controls the flux from ethanol into lipids in Drosophila larvae. A 13C NMR study. AB - The dependence of the flux in the alcohol-degrading pathway on the activity of alcohol dehydrogenase was investigated in Drosophila larvae. Third-instar larvae were supplied with [2-13C]ethanol as a dietary carbon source. Specific carbon enrichments in de novo synthesized fatty acids were determined in vitro by means of 13C nuclear magnetic resonance spectroscopy. Carbon fluxes deduced from these enrichment patterns were correlated with the in vitro alcohol dehydrogenase activities in three different Adh genotypes in seven different strains. The flux control coefficient for alcohol dehydrogenase was shown to be approximately 1.0. This indicates that the alcohol dehydrogenase gene-enzyme system in Drosophila larvae can be a major target of natural selection. PMID- 1939172 TI - The astacin family of metalloendopeptidases. AB - Molecular cloning of a human intestinal brush border metalloendopeptidase (N benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase, PPH) and a mouse kidney brush border metalloendopeptidase (meprin A) has revealed 82% identity in the NH2 terminal amino acid sequences (198 residues) of the mature enzymes. Furthermore, searching of protein sequence data bases with the inferred peptide sequences as probes revealed strong similarities to astacin, a crayfish digestive protease, and an NH2-terminal domain of a human bone morphogenetic protein (BMP-1). Meprin A and PPH both have approximately 30% identity with astacin and BMP-1. Multiple alignment analysis indicated that 37 residues, including 3 cysteine residues, are strictly conserved for the four proteins in a sequence frame equivalent to the complete 200-amino acid astacin sequence. The four proteins contain a zinc binding motif (HEXXH), found at the active site of most metalloendopeptidases, within an extended sequence of HEXXHXXGFXHE which is unique to this subgroup of metalloendopeptidases. In addition, the four proteins have 54% identity in a 24 amino acid sequence that includes the putative active site. A fifth protein, Xenopus laevis developmentally regulated protein UVS.2, also shares sequence identity with the metalloendopeptidases. These data provide strong evidence for an evolutionary relationship of these proteins. It is suggested that this new family of metalloendopeptidases be called the "astacin family." PMID- 1939173 TI - Purification and properties of an ommochrome-binding protein from the hemolymph of the tobacco hornworm, Manduca sexta. AB - A yellow-colored protein (YCP) was isolated from the hemolymph (i.e. blood) of fifth instar wandering stage larvae of Manduca sexta. The molecular mass of YCP was 31 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gel filtration chromatography suggested that native YCP was a monomer. The absorbance spectrum of YCP revealed maxima at 278 and 405 nm. Chromophore was released from YCP through denaturation of the protein with methanol and chloroform. In neutral solution and in acid, the released chromophore showed the absorbance characteristics of an ommochrome: ommatin D. In addition, the chromophore was sensitive to treatment with arylsulfatase as would be expected for ommatin D. The amino acid composition and the N-terminal sequence of YCP were determined. The YCP polypeptide chain was found to be glycosylated. Carbohydrate analysis suggested that Man and GlcNAc were present in a 3:1 ratio. Circular dichroism indicated that YCP consisted of 68% beta-pleated sheet with no alpha-helices being detected. An in vitro incubation of larval fat body in the presence of [35S]methionine indicated that this organ was the site of synthesis. Ommochromes arise in insects as end products of the metabolism of tryptophan. It is well documented that ommochromes occur in both the tissues and the excreta of insects. We propose that in M. sexta, one such tryptophan metabolite is found in the hemolymph associated with a specific protein. PMID- 1939175 TI - Redox forms of human placenta glutathione transferase. AB - Human placenta glutathione transferase (EC 2.5.1.18) pi undergoes an oxidative inactivation which leads to the formation of an inactive enzymatic form which is homogeneous in several chromatographic and electrophoretic conditions. This process is pH dependent, and it occurs at appreciable rate in alkaline conditions and in the presence of metal ions. Dithiothreitol treatment completely restores the active form. -SH titration data and electrophoretic studies performed both on the oxidized and reduced forms indicate that one intrachain disulfide is formed, probably between the two faster reacting cysteinyl groups of each subunit. By the use of a specific fluorescent thiol reagent the disulfide forming cysteines have been identified as the 47th and 101th residues. The disulfide formation causes changes in the tertiary structure of this transferase as appears by CD, UV, and fluorometric analyses; evidences are provided that one or both tryptophanyl residues of each subunit together with a number of tyrosyl residues are exposed to a more hydrophilic environment in the oxidized form. Moreover, electrophoretic data indicate that the subunit of the oxidized enzyme has an apparent molecular mass lower than that of the reduced transferase, thereby confirming structural differences between these forms. PMID- 1939176 TI - Movement of zymosterol, a precursor of cholesterol, among three membranes in human fibroblasts. AB - Where examined, cholesterol is synthesized in the endoplasmic reticulum; however, its precursor, zymosterol, is found mostly in the plasma membrane. The novel implication of these disparate findings is that zymosterol circulates within the cell. In tracing its movements, we have now established the following: (a) in human fibroblasts, zymosterol is converted to cholesterol solely in the rough ER. (b) Little or no zymosterol or cholesterol accumulates in the rough ER in vivo. (c) Newly synthesized zymosterol moves to the plasma membrane without a detectable lag and with a half-time of 9 min, about twice as fast as cholesterol. (d) The pool of radiolabeled zymosterol in the plasma membrane turns over rapidly, faster than does intracellular cholesterol. Thus, plasma membrane zymosterol is not stagnant. (e) [3H]Zymosterol pulsed into intact cells is initially found in the plasma membrane. It is rapidly internalized and is then converted to [3H] cholesterol. Half of the [3H]cholesterol produced returns to the plasma membrane within 30 min of the initial [3H]zymosterol pulse. (f) Nascent zymosterol accumulates in a buoyant sterol-rich intracellular membrane before it reaches the plasma membrane. This membrane also acquires nascent cholesterol, exogenous [3H]zymosterol pulsed into intact cells, and [3H]cholesterol synthesized from the exogenous [3H] zymosterol. These results suggest that at least one sterol moves rapidly and in both directions among the rough endoplasmic reticulum, a sterol-rich intracellular membrane bearing nascent cholesterol, and the plasma membrane. PMID- 1939177 TI - Processing of the papain precursor. Purification of the zymogen and characterization of its mechanism of processing. AB - The precursor of the cysteine protease papain has been expressed and secreted as propapain from insect cells infected with a recombinant baculovirus expressing a synthetic gene coding for prepropapain. This 39-kDa secreted propapain zymogen molecule is glycosylated and can be processed in vitro into an enzymatically active authentic papain molecule of 24.5 kDa (Vernet, T., Tessier, D.C., Richardson, C., Laliberte, F., Khouri, H. E., Bell, A. W., Storer, A. C., and Thomas, D. Y. (1990) J. Biol. Chem. 265, 16661-16666). Recombinant propapain was stabilized with Hg2+ and purified to homogeneity using affinity chromatography, gel filtration, and ion-exchange chromatographic procedures. The maximum rate of processing in vitro was achieved at approximately pH 4.0, at a temperature of 65 degrees C and under reducing conditions. Precursor processing is inhibited by a variety of reversible and irreversible cysteine protease inhibitors but not by specific inhibitors of serine, metallo or acid proteases. Replacement by site directed mutagenesis of the active site cysteine with a serine at position 25 also prevents processing. The inhibitor 125I-N-(2S,3S)-3-trans hydroxycarbonyloxiran-2-carbonyl-L-tyrosine benzyl ester covalently labeled the wild type papain precursor, but not the C25S mutant, indicating that the active site is accessible to the inhibitor and is in a native conformation within the precursor. Based on biochemical and kinetic analyses of the activation and processing of propapain we have shown that the papain precursor is capable of autoproteolytic cleavage (intramolecular). Once free papain is released processing can then occur in trans (intermolecular). PMID- 1939179 TI - Roles of metal ions in the maintenance of the tertiary and quaternary structure of arginase from Saccharomyces cerevisiae. AB - Arginase from Saccharomyces cerevisiae has long been known to be a metal ion requiring enzyme as it requires heating at 45 degrees C in the presence of 10 mM Mn2+ for catalytic activation. Metals are also thought to play a structural role in the enzyme, but the identity of the structural metal and its precise structural role have not been defined. Analysis of the metal ions that bind to yeast arginase by atomic absorption spectroscopy reveals that there is a weakly associated Mn2+ that binds to the trimeric enzyme with a stoichiometry of 1.04 +/ 0.05 mol of Mn2+ bound per subunit and an apparent K'D value of 26 microM at pH 7.0 and 4 degrees C. A more tightly associated Zn2+ ion can only be removed by dialysis against chelating agents. In occasional preparations, this site contained some Mn2+; however, Zn2+ and Mn2+ together bind to high affinity sites with a stoichiometry of 1.14 +/- 0.25/mol of subunit. Both the loosely associated catalytic Mn2+ ion and the more tightly associated structural Zn2+ ion confer stability to the enzyme. Removal of the weakly bound Mn2+ ion results in a 3 degree C decrease in the midpoint of the thermal transition (T 1/2) (from 57 by 54 degrees C) as monitored by UV difference absorption spectroscopy. Removal of the tightly bound Zn2+ ion produces a 19 degrees C decrease in T 1/2 (to 38 degrees C). Similar results are obtained by circular dichroism measurements. When the Zn2+ ion is removed, the steady-state fluorescence intensity increases 100% as compared to the holoenzyme, with a shift in the emission maximum from 337 to 352 nm. This suggests that in the folded trimeric metalloenzyme, the tryptophan fluorescence is quenched and that upon removal of the structural metal, the quenching is relieved as tryptophan residues become exposed to more polar environments. Equilibrium sedimentation experiments performed after dialysis of the enzyme against EDTA demonstrate that arginase exists in a reversible monomer trimer equilibrium, in the absence of metal ions, with a KD value of 5.05 x 10( 11) M2. In contrast, the native enzyme exists as a trimer with no evidence of dissociation when Mn2+ and Zn2+ are present (Eisenstein, E., Duong, L.T., Ornberg, R. L., Osborne, J.C., Jr., and Hensley, P. (1986) J. Biol. Chem. 261, 12814-12819). In summary, the study presented here demonstrates that binding of a weakly bound Mn2+ ion confers catalytic activity. In contrast, binding of a more tightly associated Zn2+ ion confers substantial stability to the tertiary and quaternary structure of the enzyme. PMID- 1939178 TI - Expression of calreticulin in Escherichia coli and identification of its Ca2+ binding domains. AB - Recombinant calreticulin and discrete domains of calreticulin were expressed in Escherichia coli, using the glutathione S-transferase fusion protein system, and their Ca2+ binding properties were determined. Native calreticulin bound 1 mol of Ca2+/mol of protein with high affinity, and also bound approximately 20 mol of Ca2+/mol of protein with low affinity. Both Ca2+ binding sites were present in the recombinant calreticulin indicating that proper folding of the protein was achieved using this system. Calreticulin is structurally divided into three distinct domains: the N-domain encompassing the first 200 residues; the P-domain which is enriched in proline residues (residue 187-317); and the C-domain which covers the carboxyl-terminal quarter of the protein (residues 310-401), and contains a high concentration of acidic residues. These domains were expressed in E. coli, isolated, and purified, and their Ca2+ binding properties were analyzed. The C-domain bound approximately 18 mol of Ca2+/mol of protein with a dissociation constant of approximately 2 mM. The P-domain bound approximately 0.6 1 mol of Ca2+/mol of protein with a dissociation constant of approximately 10 microM. The P-domain and the C-domain, when expressed together as the P+C-domain, bound Ca2+ with both high affinity and low affinity, reminiscent of both full length recombinant calreticulin and native calreticulin. In contrast the N domain, did not bind any detectable amount of 45Ca2+. We conclude that calreticulin has two quite distinct types of Ca2+ binding sites, and that these sites are in different structural regions of the molecule. The P-domain binds Ca2+ with high affinity and low capacity, whereas the C-domain binds Ca2+ with low affinity and high capacity. PMID- 1939180 TI - The processing of human proinsulin and chicken proalbumin by rat hepatic vesicles suggests a convertase specific for X-Y-Arg-Arg or Arg-X-Y-Arg sequences. AB - Vesicles from rat and chicken livers contain very similar Ca2(+)-dependent proteases that respectively cleave (human) proalbumin at an Arg-Arg site and chicken proalbumin at an Arg-Phe-Ala-Arg site. Similar Ca2(+)-dependent proteases are also present in pancreatic secretory granules and cleave proinsulin at two sites, Arg-Arg and Lys-Arg. The mammalian liver processes a large variety of different proproteins and in order to assess its processing site requirements, we investigated the ability of rat hepatic vesicle extracts to cleave purified chicken proalbumin and human proinsulin. Despite having only a monobasic processing site, chicken proalbumin was cleaved faster than human proalbumin which not only contains a dibasic site, but has an identical propeptide to that of the rat's own proalbumin. Human proinsulin was processed by the rat liver extracts; however, no mature insulin was produced. Cleavage occurred in only one place, presumably the Arg-Arg site at the B-C chain junction. This suggests that the mammalian liver might not contain a Type II Lys-Arg-directed convertase, only a Type I Arg-Arg-specific enzyme. The Type I enzyme that cleaves human proalbumin appears to be the same activity that cleaves chicken proalbumin, suggesting a specificity for either X-Y-Arg-Arg or Arg-X-Y-Arg sequences. This proposal is in keeping with the processing site motif of some 16 different proproteins that are known to be processed in the liver and is entirely consistent with the known in vivo specificity of the enzyme defined by naturally occurring variants of human proproteins. PMID- 1939181 TI - Mechanism of the potentiating effect of ribavirin on the activity of 2',3' dideoxyinosine against human immunodeficiency virus. AB - Ribavirin enhances the anti-human immunodeficiency virus activity of 2',3' dideoxyinosine (ddIno) in MT-4, CEM and peripheral blood lymphocyte cells. Ribavirin causes an increase in the levels of IMP, the presumed phosphate donor for the conversion of ddIno to ddIMP by 5'-nucleotidase. Consequently, ribavirin stimulates the conversion of ddIno to its antivirally active metabolite ddATP. Ribavirin also causes a marked depletion of the guanine nucleotide pools. The increase in IMP pool levels may result from (i) a direct inhibitory effect of ribavirin 5'-monophosphate on IMP dehydrogenase (which converts IMP to XMP) and (ii) an indirect inhibition of adenylosuccinate synthetase by the decreased GTP and dGTP pools (since GTP is an obligatory cofactor in the conversion of IMP to succinyl AMP). GTP depletion plays a key role in the accumulation of IMP and the resultant higher rate of ddIno phosphorylation to ddIMP and eventually ddATP. Our findings are in agreement with the observations that guanosine and 2' deoxyguanosine, but not 2'-deoxyadenosine, reverse (i) the stimulatory effect of ribavirin on the anti-human immunodeficiency virus activity of ddIno and (ii) the accumulation of endogenous IMP pools as well as accumulation of [3H]IMP from exogenous [3H]hypoxanthine in ribavirin-treated cells. PMID- 1939182 TI - Effects of farnesylcysteine analogs on protein carboxyl methylation and signal transduction. AB - Several proteins associated with signal transduction in eukaryotes are carboxyl methylated at COOH-terminal S-farnesylcysteine residues. These include members of the Ras superfamily and gamma-subunits of heterotrimeric G-proteins. The enzymes that catalyze the carboxyl methylation reaction also methylate small molecules such as N-acetyl-S-trans, trans-farnesyl-L-cysteine (AFC). AFC inhibits carboxyl methylation of p21ras and related proteins both in vitro and in vivo. Saturating concentrations of AFC cause a greater than 80% inhibition of chemotactic responses of mouse peritoneal macrophages. Our results suggest that carboxyl methylation may play a role in the regulation of receptor-mediated signal transduction processes in eukaryotic cells. PMID- 1939183 TI - The refined crystal structure of alpha-cobratoxin from Naja naja siamensis at 2.4 A resolution. AB - The crystal structure of the "long" alpha-neurotoxin alpha-cobratoxin was refined to an R-factor of 19.5% using 3271 x-ray data to 2.4-A resolution. The polypeptide chain forms three loops, I, II, III, knotted together by four disulfide bridges, with the most prominent, loop II, containing another disulfide close to its lower tip. Loop I is stabilized by one beta-turn and two beta-sheet hydrogen bonds; loop II by eight beta-sheet hydrogen bonds, with the tip folded into two distorted right-handed helical turns stabilized by two alpha-helical and two beta-turn hydrogen bonds; and loop III by hydrophobic interactions and one beta-turn. Loop II and one strand of loop III form an antiparallel triple-pleated beta-sheet, and tight anchoring of the Asn63 side chain fixes the tail segment. In the crystal lattice, the alpha-cobratoxin molecules dimerize by beta-sheet formation between strands 53 and 57 of symmetry-related molecules. Because such interactions are found also in a cardiotoxin and alpha-bungarotoxin, this could be of importance for interaction with acetylcholine receptor. PMID- 1939184 TI - Mechanism of mutual activation of the tryptophan synthase alpha and beta subunits. Analysis of the reaction specificity and substrate-induced inactivation of active site and tunnel mutants of the beta subunit. AB - The origin of reaction and substrate specificity and the control of activity by protein-protein interaction are investigated using the tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium. We have compared some spectroscopic and kinetic properties of the wild type beta subunit and five mutant forms of the beta subunit that have altered catalytic properties. These mutant enzymes, which were engineered by site-directed mutagenesis, have single amino acid replacements in either the active site or in the wall of a tunnel that extends from the active site of the alpha subunit to the active site of the beta subunit in the alpha 2 beta 2 complex. We find that the mutant alpha 2 beta 2 complexes have altered reaction and substrate specificity in beta-elimination and beta-replacement reactions with L-serine and with beta-chloro-L-alanine. Moreover, the mutant enzymes, unlike the wild type alpha 2 beta 2 complex, undergo irreversible substrate-induced inactivation. The mechanism of inactivation appears to be analogous to that first demonstrated by Metzler's group for inhibition of two other pyridoxal phosphate enzymes. Alkaline treatment of the inactivated enzyme yields apoenzyme and a previously described pyridoxal phosphate derivative. We demonstrate for the first time that enzymatic activity can be recovered by addition of pyridoxal phosphate following alkaline treatment. We conclude that the wild type and mutant alpha 2 beta 2 complexes differ in the way they process the amino acrylate intermediate. We suggest that the wild type beta subunit undergoes a conformational change upon association with the alpha subunit that alters the reaction specificity and that the mutant beta subunits do not undergo the same conformational change upon subunit association. PMID- 1939185 TI - Crystallographic analysis of two site-directed mutants of Azotobacter vinelandii ferredoxin. AB - The crystal structure of the C24A mutant of Azotobacter vinelandii 7Fe ferredoxin (FdI) has been solved and refined at 2.0-A resolution. The structure is isomorphous to native FdI except at the site of mutation where A24 moves toward the [4Fe-4S] cluster. In spite of this inefficient packing results: three of five van der Waals contacts from the S gamma of C24 in native FdI are lost and the remaining two become longer. Consequently, the [4Fe-4S] cluster is either disordered or has a higher temperature factor (B factor) compared to the rest of the C24A FdI molecule. In addition, the entire C24A FdI structure has a higher overall B factor than native FdI. Therefore, in comparison to native FdI, the C24A mutant is isomorphous but exhibits large differences in B factor, especially at the [4Fe-4S] cluster. In contrast, the C20A FdI structure (Martin, A. G., Burgess, B. K., Stout, C. D., Cash, V. L., Dean, D. R., Jensen, G. M., and Stephens, P. J. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 598-602), which contains large structural rearrangements in the vicinity of the [4Fe-4S] cluster, exhibits essentially no change in B factor. The conformational change observed at residue 24 is similar in both C24A and C20A FdI structures. The solvent accessibility of the Fe atoms in the [3Fe-4S] and [4Fe-4S] clusters is similar in C24A, C20A, and native FdI. PMID- 1939186 TI - Purification and characterization of GDP-L-fucose-N-acetyl beta-D-glucosaminide alpha 1----6fucosyltransferase from cultured human skin fibroblasts. Requirement of a specific biantennary oligosaccharide as substrate. AB - GDP-L-fucose-N-acetyl-beta-D-glucosaminide alpha 1----6fucosyltransferase which catalyzes the transfer of fucose from GDP-L-fucose to the asparagine-linked N acetyl-beta-D-glucosamine of N-linked glycoproteins has been purified 37,000-fold from cultured human skin fibroblasts. The Km values for the substrate asialoagalactotransferrin glycopeptide, and GDP-L-fucose were 66 and 4.2 microM, respectively. The Vmax was 1.4 mumols/mg/min. The key step in enzyme purification was affinity chromatography using the immobilized substrate asialoagalactotransferrin glycopeptide-CH-Sepharose. The affinity-purified enzyme had a minimum substrate requirement for a biantennary oligosaccharide with GlcNAc in terminal position, having a Km value of 55 microM. It was heretofore unexpected that the oligosaccharide would serve as substrate, since the site of enzyme activity is GlcNAc-1-linked to Asn. Although the presence of amino acids on this oligosaccharide enhanced the activity 3-fold, it is proposed that this may be the result of an alpha/beta anomeric mixture (2:1) of oligosaccharide used in these studies with only the beta anomer active as substrate. The implication is that the amino acid is required only to retain the beta anomeric position of the substrate. Removal of GlcNAc or addition of Gal to either the oligosaccharide or glycopeptide destroyed the ability to serve as substrates. In addition, di-N acetylchitobiose, tri-N-acetylchitotriose and GlcNAc beta 1----Asn were nonpermissible substrates. This rigid substrate requirement is unique among fucosyltransferases thus far reported, since the natural substrates for the other enzymes may be substituted by one of several disaccharides. PMID- 1939187 TI - Protein topography of Sulfolobus solfataricus ribosomes by cross-linking with 2 iminothiolane. Sso L12e, Sso L10e, and Sso L11e are neighbors. AB - Large ribosomal subunits from Sulfolobus solfataricus were cross-linked with 2 iminothiolane in order to investigate the arrangement of proteins in the region containing the multicopy acidic protein Sso L12e, the protein homologous to Escherichia coli L7/L12. Proteins from cross-linked 50 S subunits were extracted and fractionated by chromatography on CM-cellulose. Fractions containing Sso L12e were analyzed by "diagonal" (two-dimensional reducing/nonreducing) dodecyl sulfate polyacrylamide gel electrophoresis. Sso L12e appeared in cross-linked homodimers and also in cross-linked complexes that contained Sso L10e, the protein equivalent to E. coli L10. In addition, Sso L12e was found in cross-links to L4, L6a, L26, and L29. N-terminal sequences obtained for L6a and L26 showed them to have significant homologies to E. coli proteins L11 and L23, respectively. The results indicate the presence in this archaebacterial ribosome of Sso L12e dimers and their location near Sso L10e and Sso L11e. The Sso L12e L29 (Sso L23e) cross-link suggests proximity between components of the factor binding and peptidyltransferase domains, since E. coli L23 is a protein affinity labeled by puromycin. The (Sso L12e)4-Sso L10 pentameric complex, identified previously from studies in solution, appears to represent correctly the arrangement of these proteins in the ribosome. The occurrence in the archaebacterial ribosome of this unique structural element, similar to those shown previously in eubacteria and eukaryotes, reinforces the concept that the protein quaternary structure of the ribosomal factor-binding domain is highly conserved. PMID- 1939188 TI - Oscillations of intracellular calcium induced by vasopressin in individual fura-2 loaded mesangial cells. Frequency dependence on basal calcium concentration, agonist concentration, and temperature. AB - Intracellular free calcium concentration ([Ca2+]i) was measured in fura-2-loaded single rat mesangial cells by dual wavelength spectrofluorometry. Stimulation with arginine vasopressin (AVP) caused an initial sharp rise of [Ca2+]i followed by repetitive spikes. The frequency of the oscillations was dependent on the concentration of AVP. At 0.1, 1.0, 10.0, and 100.0 nM AVP, the frequencies of oscillations were 0.17 +/- 0.05 (n = 6), 0.32 +/- 0.05 (n = 6), 0.49 +/- 0.05 (n = 6), and 0.48 +/- 0.05 min-1 (n = 5), respectively. Reduction in extracellular [Ca2+] reduced the frequency of AVP-induced oscillations but did not abolish the oscillations. The frequency of calcium oscillations, upon stimulation with 1.0 nM AVP, was directly correlated with the basal [Ca2+]i prior to stimulation. Oscillation frequency increased with increasing temperature. An Arrhenius plot between 24 and 37 degrees C indicated a strong temperature dependency of the oscillations with a Q10 of 3.0. Protein kinase C stimulation by active phorbol esters inhibited AVP-induced calcium oscillations but not the initial [Ca2+] response to AVP. These observations are consistent with a model incorporating a feedback loop linking [Ca2+]i to the mechanism of [Ca2+]i increase. Ca(2+) induced Ca2+ release may be involved, whereby inositol 1,4,5-trisphosphate (inositol 1,4,5-P3) formation releases Ca2+ from an inositol 1,4,5-P3-sensitive pool, with subsequent Ca2+ uptake and release from an inositol 1,4,5-P3 insensitive pool. PMID- 1939189 TI - The hydrophobic photoreagent 3-(trifluoromethyl)-3-m-([125I] iodophenyl) diazirine is a novel noncompetitive antagonist of the nicotinic acetylcholine receptor. AB - We have shown previously that the lipophilic photoreagent 3-(trifluoromethyl)3-m ([125I]iodophenyl)-diazirine ([125I]TID) photolabels all four subunits of the Torpedo nicotinic acetylcholine receptor (AChR) and that greater than 70% of this photoincorporation is inhibited by cholinergic agonists and some noncompetitive antagonists, including histrionicotoxin (HTX), but not phencyclidine (PCP; White, B.H., and Cohen, J.B. (1988) Biochemistry 27, 8741-8751). We have now examined the effects of nonradioactive TID on (a) AChR photoincorporation of [125I]TID, (b) AChR-mediated ion transport, and (c) AChR binding of several cholinergic ligands. We find that TID inhibits [125I]TID photoincorporation into the AChR to the same extent as carbamylcholine. The saturable component of [125I]TID photolabeling is half-maximal at 4 microM [125I]TID with 0.5 mol specifically incorporated per mol of AChR after 30 min photolysis with 60 microM [125I]TID. Repeated labeling of membranes at a fixed [125I]TID concentration gave results consistent with a maximal incorporation of one [125I]TID molecule per AChR. Nonradioactive TID also noncompetitively inhibits agonist-stimulated 22Na+ efflux from Torpedo vesicles with an IC50 of 1 microM. Furthermore, TID inhibits allosterically the binding of [3H]HTX, decreasing its affinity for the AChR 5 fold both in the presence and absence of agonist. In contrast, TID has little effect on [3H]PCP binding in the absence of agonist but completely inhibits it in the presence of agonist. TID enhances the cooperativity of [3H]nicotine binding. [125I]TID is thus a photoaffinity label for a novel noncompetitive antagonist binding site on the AChR that is linked allosterically to the binding sites of both agonists and other noncompetitive antagonists. The [125I]TID site is presumably located within the central pore of the AChR. PMID- 1939190 TI - Functional characteristics of the rrnD promoters of Escherichia coli. AB - The function of the tandem rrnD promoters (P1, P2) of Escherichia coli, which are highly efficient in directing rRNA synthesis, was studied in vitro using the strong hybrid promoter PtacI as a reference. One of the characteristics of the rrnD promoters is a pronounced instability of binary and initiating complexes formed with RNA polymerase. The rate of productive complex formation and of chain initiation at these promoters was found to be limited by a step in binary complex transitions with an apparent first-order rate constant equal to 3.9 x 10(-2) s-1. A comparison of this rate with that determined previously by filter binding assays (Gourse, R. (1988) Nucleic Acids Res. 16, 9789-9809) suggests that the rate-limiting step is a conversion of an intermediate species of open complex to one that is efficient in productive initiation. The slow rate of this reaction and the instability of open complexes account for the relatively low competitive strengths of the rrnD promoters. However, this limitation of rrn promoter function changes with promoter occupancy because the rate of chain initiation increased after completion of the first round of initiation. Despite their poor competitive strength, the rrnD promoters are more productive than PtacI at nonlimiting RNA polymerase concentrations. This can be ascribed to the different rates with which RNA polymerases leave PtacI and the rrnD promoters. These functional differences of the promoters are consistent with a "stressed intermediate" model of chain initiation (Straney, D.C., and Crothers, D.M. (1987) J. Mol. Biol. 193, 267-278) which predicts that rapid clearance of the rrn promoters is mechanistically related to the instability of the binary complexes. PMID- 1939191 TI - Mechanism of bovine liver S-adenosylhomocysteine hydrolase. Steady-state and pre steady-state kinetic analysis. AB - The kinetic mechanism of S-adenosylhomocysteine hydrolase was investigated by stopped-flow spectrofluorometry at pH 7.0 and 25 degrees C. Pre-steady-state kinetic steps were identified with chemical steps proposed for the mechanism of this enzyme (Palmer, J.L., and Abeles, R.H. (1979) J. Biol. Chem. 254, 1217 1226). The steady-state kinetic constants for the hydrolysis or synthesis of S adenosylhomocysteine were in good agreement with those values calculated from the pre-steady-state rate constants. The equilibrium constant for dehydration of 3' ketoadenosine to 3'-keto-4',5'-dehydroadenosine on the enzyme was 3. The analogous equilibrium constant for addition of L-homocysteine to S-3'-keto-4',5' dehydroadenosylhomocysteine on the enzyme was 0.3. The elimination of H2O from adenosine in solution had an equilibrium constant of 1.4 (aH2O = 1). Thus, the equilibrium constants for these elimination reactions on the enzyme were probably not perturbed significantly from those in solution. The equilibrium constant for the reduction of enzyme-bound NAD+ by adenosine was 8, and the analogous constant for the reduction of the enzyme by S-adenosylhomocysteine was 4. The equilibrium constant for the reduction of NAD+ by a secondary alcohol in solution was 5 x 10( 5) at pH 7.0. Consequently, the reduction of enzyme-bound NAD+ by adenosine was 10(5)-fold more favorable than the reduction of free NAD+. The magnitude of the first-order rate constants for the interconversion of enzyme-bound intermediates varied over a relatively small range (3-80 s-1). Similarly, the magnitude of the equilibrium constants among enzyme-bound intermediates varied over a narrow range (0.3-10). These results were consistent with the overall reversibility of the reaction. PMID- 1939192 TI - The assignment of carbon monoxide association rate constants to the alpha and beta subunits in native and mutant human deoxyhemoglobin tetramers. AB - The association kinetics of CO binding to site-directed mutants of human deoxyhemoglobin were measured by stopped-flow rapid mixing techniques at pH 7.0, 20 degrees C. Hemoglobin tetramers were constructed from one set of native subunits and one set of mutated partners containing His(E7) to Gly, Val(E11) to Ala, or Val(E11) to Ile substitutions. The reactivity of beta Cys93 with p hydroxymercuribenzoate was measured to ensure that the mutant deoxyhemoglobins were capable of forming T-state quaternary conformations. Time courses for the complete binding of CO were measured by mixing the deoxygenated proteins with a 5 fold excess of ligand in the absence and presence of inositol hexaphosphate. Association rate constants for the individual alpha and beta subunits in the T state conformation were assigned by measuring time courses for the reaction of a small, limiting amount of CO with a 20-fold excess of deoxyhemoglobin (i.e. Hb4 + CO----Hb4(CO)). The effects of the E7 and E11 mutations in T-state alpha subunits were qualitatively similar to those observed for the same subunit in the R-state (Mathews, A.J., Rohlfs, R.J., Olson, J.S., Tame, J., Renaud, J-P., and Nagai, K. (1989) J. Biol. Chem. 264, 16573-16583). The alpha His58(E7) to Gly and Val62(E11) to Ala substitutions caused 80- and 3-fold increases, respectively, in k'CO for T-state alpha subunits, and the alpha Val62(E11) to Ile mutation caused a 3-fold decrease. The beta His63(E7) to Gly and Val67(E11) to Ala substitutions produced 70- and 8-fold increases, respectively, in k'CO for T-state beta subunits whereas these same mutations caused little effect on the rate of CO binding to R-state beta subunits. The beta Val67(E11) to Ile mutation produced the same large effect, a 23-fold reduction in k'CO, in both quaternary conformations of beta subunits. These kinetic results can be interpreted qualitatively in terms of differences between the alpha and beta subunits in the deoxy and liganded crystal structures of human hemoglobin (Perutz, M.F. (1990) Annu. Rev. Physiol. 52, 1-25). Both the structural and functional data suggest that the distal portion of the beta heme pocket is tightly packed in deoxyhemoglobin whereas the CO binding site in R-state beta subunits is much more open. In contrast, the distal portion of the alpha heme pocket is restricted sterically in both quaternary states.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1939193 TI - The Na(+)-independent Ca2+ efflux mechanism of liver mitochondria is not a passive Ca2+/2H+ exchanger. AB - Whether the Na(2+)-independent Ca2+ efflux mechanism of liver mitochondria is a Ca2+/2H+ exchanger and whether this exchanger is a passive mechanism have been controversial since shortly after the discovery of this mechanism. Here, a new approach to determining if the mechanism is passive is developed based on the energy available to a passive Ca2+/2H+ exchanger. Conditions are identified in which the Na(+)-independent Ca2+ efflux mechanism transports Ca2+ out of mitochondria against a Ca2+ gradient many times greater than that possible for a passive Ca2+/2H+ exchanger, thus ruling this out as a possible mechanism. PMID- 1939194 TI - Mechanism-based inactivation of alanine racemase by 3-halovinylglycines. AB - Alanine racemase, an enzyme important to bacterial cell wall synthesis, is irreversibly inactivated by 3-chloro- and 3-fluorovinylglycine. Using alanine racemase purified to homogeneity from Escherichia coli B, the efficient inactivation produced a lethal event for every 2.2 +/- 0.2 nonlethal turnovers, compared to 1 in 800 for fluoroalanine. The mechanism of inhibition involves enzyme-catalyzed halide elimination to form an allenic intermediate that partitions between reversible and irreversible covalent adducts, in the ratio 3:7. The reversible adduct (lambda max = 516 nm) decays to regenerate free enzyme with a half-life of 23 min. The lethal event involves irreversible alkylation of a tyrosine residue in the sequence -Val-Gly-Tyr-Gly-Gly-Arg. The second-order rate constant for this process with D-chlorovinylglycine (122 +/- 14 M-1 s-1), the most reactive analog examined, is faster than the equivalent rate constant for D-fluoroalanine (93 M-1 s-1). The high killing efficiency and fast turnover of these mechanism-based inhibitors suggest that their design, employing the haloethylene moiety to generate a reactive allene during catalysis, could be extended to provide useful inhibitors of a variety of enzymes that conduct carbanion chemistry. PMID- 1939195 TI - The unique feature of dog liver cytosolic glutathione S-transferases. An isozyme not retained on the affinity column has the highest activity toward 1,2-dichloro 4-nitrobenzene. AB - In the adult dog liver cytosol we identified four glutathione S-transferase (GST) subunits, Yd1 (Mr 26,000), Yd2 (Mr 27,000), Yd3 (Mr 28,000), and Ydf (Mr 27,400), and purified GST forms comprising Yd1, Yd2, and Yd3, to apparent homogeneity. Unlike rat transferases the enzyme activity toward 1,2-dichloro-4-nitrobenzene (DCNB) was not retained on the affinity column. Thus the DCNB-active enzyme, GST YdfYdf, from the flow-through fraction of the affinity column was also purified to homogeneity by gel filtration, DE52 chromatography, chromatofocusing, and hydroxylapatite column chromatography. Immunoblot analysis of dog GSTs revealed that the subunits Yd1, Yd2, and Yd3 belong to the pi, alpha, and mu class, respectively. On the contrary, Ydf had no reactivity with antibodies raised against any of the three classes of GST. Each subunit, Yd1, Yd2, Yd3, and Ydf, was distinguishable by its own retention time on reverse-phase high performance liquid chromatography. N-terminal amino acid sequences of the dog GSTS Yd1Yd1 and Yd3Yd3 revealed a high degree of homology to the pi and mu class transferases from rat, human, and mouse, respectively, while the N terminus of Yd2Yd2 is blocked. N-terminal amino acid sequences of GST YdfYdf showed no homology to any of the three classes of GST. The most significant property noted of GST YdfYdf is the high specific activity toward DCNB, exceeding by 1 order of magnitude the corresponding values for the known mu class GSTs. The present results strongly suggest that dog GST YdfYdf is a unique enzyme distinct from the hitherto characterized GST isozymes. PMID- 1939196 TI - Abnormal tau proteins from Alzheimer's disease brains. Purification and amino acid analysis. AB - Abnormal tau proteins (PHF-tau) were isolated from Alzheimer's disease brains by treatment of paired helical filament enriched-fractions with perchloric acid and boiling of the acid precipitable fraction with beta-mercaptoethanol. These proteins were purified further by a second perchloric acid treatment. The purified PHF-tau proteins were soluble in buffers devoid of sodium dodecyl sulfate. However, they were similar to the abnormal tau extracted from paired helical filaments with sodium dodecyl sulfate, also named A68, in molecular mass (68, 64, and 60 kDa), isoelectric point (pI 5.5-6.5), reactivity with anti-tau antibodies, and in requirement for alkaline phosphatase treatment to bind the Tau 1 antibody. Compared to normal tau, the soluble PHF-tau contained 100% more glycine and 35% less lysine residue. The results suggest that besides phosphorylation other types of modification may be involved in differentiating PHF-tau from normal tau. PMID- 1939197 TI - Three distinct DNA ligases in mammalian cells. AB - The major DNA ligase of proliferating mammalian cells, DNA ligase I, catalyzes the joining of single strand breaks in double stranded DNA and is active on a synthetic substrate of oligo(dT) hybridized to poly(dA). DNA ligase I does not catalyze the joining of an oligo(dT).poly(rA) substrate. Two additional DNA ligases, II and III, which can act on the latter substrate have been purified from calf thymus. DNA ligase II, which has been described previously, is a 72-kDa protein. DNA ligase III migrates as a 100-kDa protein in denaturing gel electrophoresis. Structural, immunochemical, and catalytic studies on the three DNA ligase activities strongly indicate that they are the products of three different genes. PMID- 1939198 TI - Glycolytic enzymes and a GLUT-1 glucose transporter in the outer segments of rod and cone photoreceptor cells. AB - The presence of glycolytic enzymes and a GLUT-1-type glucose transporter in rod and cone outer segments was determined by enzyme activity assays, glucose uptake measurements, Western blotting, and immunofluorescence microscopy. Enzyme activities of six glycolytic enzymes including hexokinase, phosphofructokinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, pyruvate kinase, and lactate dehydrogenase, were found to be present in purified rod outer segment (ROS) preparations. Immunofluorescence microscopy of bovine and chicken retina sections labeled with monoclonal antibodies against glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase, and lactate dehydrogenase have confirmed that these enzymes are present in rod and cone outer segments and not simply contaminants from the inner segments or other cells. Rod outer segments were also found to contain glucose transport activity as detected by 3-O [14C]methylglucose uptake and exchange. The glucose transporter had a Km of 6.3 mM and a Vmax of 0.15 nmol of 3-O-methylglucose/s/mg of ROS membrane protein for net uptake and a Km of 29 mM and a Vmax of 1.06 nmol of 3-O-methylglucose/s/mg of ROS membrane protein for equilibrium exchange. These Km values for net uptake and equilibrium exchange are similar to values obtained for human red blood cells and are characteristic of GLUT-1-type glucose transporter. The transport was inhibited by both cytochalasin B and phloretin. Western blot analysis and immunofluorescence microscopy using type-specific glucose transporter antibodies indicated that both rod and cone outer segment plasma membranes have a GLUT-1 glucose transporter of Mr 45K as found in red blood cells and brain microsomal membranes. Solid-phase radioimmune competitive inhibition studies indicated that rod outer segment plasma membranes contained 15% the number of glucose transporters found in human red blood cell membranes and had an estimated density of 400 glucose transporter per micron2 of plasma membrane. These studies support the view that outer segments can generate energy in the form of ATP and GTP by anaerobic glycolysis to supply at least some of the energy requirements for phototransduction and other metabolic processes. PMID- 1939200 TI - Activation of casein kinase II by sphingosine. AB - Sphingosine activates casein kinase II in the presence of endogenous substrates as well as a synthetic peptide substrate. The activation response occurred between 12 and 25 micrograms/ml sphingosine and exhibited positive cooperativity with a Hill coefficient of 3.0. Sphingosine not only increased the Vmax of casein kinase II but decreased the Km(app) for the peptide substrate from 0.5 to 0.08 mM. In contrast, the Km(app) for MgCl2 was increased from 0.12 to 0.7 mM. Consequently, sphingosine altered significantly several parameters which determine casein kinase II activity. The effect of sphingosine was relatively specific, inasmuch as related lipids were less potent activators or largely ineffective in stimulating casein kinase II. On the other hand, the effect of sphingosine itself could be potentiated or inhibited by other lipids. Ceramide and sphingosylphosphorylcholine augmented the sphingosine effect. Phospholipids alone did not alter the activity of casein kinase II significantly, but abolished enzyme activation by sphingosine with different potencies (phosphatidylserine greater than phosphatidylethanolamine greater than phosphatidylinositol greater than phosphatidylcholine). Moreover, the sphingosine effect could be abrogated by KCI and NaCl, which alone are known to induce enzyme activation and dissociation of aggregated casein kinase II protein; LiCl and NH4Cl also inhibited the sphingosine effect. Polyamines, known activators of casein kinase II, partially mimicked the effect of sphingosine on endogenous polypeptide phosphorylation but failed to do so with the peptide substrate. These observations demonstrate that sphingosine is a potent activator of casein kinase II. The potential pharmacological and physiological modulation of casein kinase II by sphingoid bases is discussed. PMID- 1939199 TI - The murine adenosine deaminase promoter requires an atypical TATA box which binds transcription factor IID and transcriptional activity is stimulated by multiple upstream Sp1 binding sites. AB - We have explored the template and factor requirements for in vitro transcription of the GC-rich promoter of the murine adenosine deaminase gene. The core promoter consists of an A-rich sequence (TAAAAAA) 27 base pairs upstream of the initiation site which binds transcription factor IID (TFIID) and a high affinity Sp1 binding site located 27 base pairs further upstream. Multiple upstream elements increased core promoter activity 20-fold and correspond to protected regions in DNase I footprinting assays with purified Sp1 protein. Internal deletion of the TA6 element alone eliminated transcription in spite of the presence of all other promoter elements including four Sp1 binding sites. Recombinant human TFIID supported weak basal transcription in heat-treated nuclear extracts whereas a partially purified TFIID fraction from HeLa cells reconstituted a maximal level of transcription. Inclusion of 12 base pairs immediately adjacent to the proximal Sp1 site resulted in a 5-fold boost in transcriptional activity and corresponds to a second Sp1 binding site. These results serve as a basis for further exploration of the factors involved in the developmental and selective high level tissue expression of the murine adenosine deaminase gene. PMID- 1939201 TI - Crystal structure of recombinant rabbit interferon-gamma at 2.7-A resolution. AB - The crystal structure of recombinant rabbit interferon-gamma was solved by the multiple isomorphous replacement technique at 2.7-A resolution and refined to a crystallographic R-factor of 26.2%. The interferon crystallizes with one-half of the functional dimer in the asymmetric unit, with the two polypeptide chains of the dimer related by a crystallographic 2-fold symmetry axis. The structure is predominantly alpha-helical with extensive interdigitation of the alpha-helical segments of the two polypeptide chains. PMID- 1939202 TI - Phosphorylation of neurofilament H subunit at the tail domain by CDC2 kinase dissociates the association to microtubules. AB - We sought the mammalian neurofilament tail domain-specific kinase. Several well known kinases including cAMP-dependent protein kinase, protein kinase C, Ca(2+) calmodulin-dependent protein kinase II, casein kinase I, and casein kinase II phosphorylated the high (NF-H) and middle molecular mass subunit (NF-M) of bovine neurofilaments, but they did not reduced the electrophoretic mobility of the dephosphorylated form of NF-M and NF-H by phosphorylation nor was the amount of phosphorylation increased by dephosphorylation of NF proteins, indicating that the phosphorylation sites by these kinases are not major in vivo phosphorylation sites at the tail domain. In contrast, cdc2 kinase phosphorylated specifically the dephosphorylated form of NF-H. 4 mol of phosphates were incorporated per mol of NF-H and this phosphorylation returned the electrophoretic mobility of the dephosphorylated form of NF-H to the position of the isolated, fully phosphorylated form of NF-H. Furthermore, the phosphorylation by cdc2 kinase dissociated the binding of dephosphorylated NF-H to microtubules. Phosphorylation sites were located at the carboxyl-terminal tail domain. The KSPXK motif, but not KSPXX, in the repetitive sequence was suggested to be the phosphorylation site by using synthetic peptides. PMID- 1939203 TI - Insulin-stimulated serine and threonine phosphorylation of the human insulin receptor. An assessment of the role of serines 1305/1306 and threonine 1348 by their replacement with neutral or negatively charged amino acids. AB - Insulin promotes insulin receptor beta-subunit phosphorylation on tyrosine, serine, and threonine residues in a variety of cells, including simian COS cells which transiently express human insulin receptors following transfection with a cDNA encoding the wild-type receptor protein. To examine the potential roles of serines 1305 and 1306 and threonine 1348 as sites of insulin-stimulated phosphorylation in these cells, these residues (i.e. either serines 1305 and 1306, or threonine 1348) were replaced with neutral (alanine) or negatively charged (aspartate) amino acids. Following transient expression of each of these mutant receptors in COS cells, two-dimensional phosphopeptide mapping reveals that threonine 1348 is the major, if not the only, insulin-stimulated threonine phosphorylation site. In contrast, while serines 1305 and/or 1306 are phosphorylated in an insulin-dependent manner, these sites comprise only a minor proportion of insulin receptor serine phosphorylation in these cells. Substitution of either serines 1305 and 1306 or threonine 1348 with neutral or negatively charged amino acids has no effect on insulin-stimulated tyrosine autophosphorylation of these mutant receptors in intact cells. Furthermore, insulin-stimulated exogenous protein-tyrosine kinase activity of the mutant receptors is unaffected, as assessed following either phosphorylation of receptors in intact cells or following immunopurification of receptors and their autophosphorylation in vitro. PMID- 1939204 TI - A calmodulin-binding peptide of caldesmon. AB - Caldesmon is a major actin-binding protein identified in smooth muscle and many non-muscle cells. It also interacts with calmodulin and a number of other acidic proteins. We have shown previously that the polypeptide stretch from Val629 to Ser666 near the C terminus contains a calmodulin binding site (Wang, C.-L. A., Wang, L.-W. C., Xu, S., Lu, R. C., Saavedra-Alanis, V., and Bryan, J. (1991) J. Biol. Chem. 266, 9166-9172). On the other hand, Bartegi et al. (Bartegi, A., Fattoum, A., Derancourt, J., and Kassab, R. (1990) J. Biol. Chem. 265, 15231 15238) reported a cyanogen bromide fragment beginning at Trp659 which is also capable of binding both calmodulin and actin. A comparison of the overlapping sequence between these two peptides suggests that this calmodulin binding site is localized in a 7-residue segment, 659Trp-Glu-Lys-Gly-Asn-Val-Phe665. We have chemically synthesized an 18-residue peptide (GS17C, from Gly651 to Ser667 with an added cysteine at the C terminus) that contains this segment. This peptide was purified by high performance liquid chromatography and labeled with fluorescent probes at the terminal cysteine residue. We found that GS17C indeed binds calmodulin in a Ca(2+)-dependent manner (Kd = 8 x 10(-7) M) and appears to compete with caldesmon. Interestingly, this synthetic peptide also co-sediments with F-actin, binding to actin being displaceable by calmodulin, as in the case of the native caldesmon. But GS17C does not have any effect on the actomyosin ATPase activity, indicating that this peptide segment does not contain the inhibitory region. PMID- 1939205 TI - Determinants of regional sucrase-isomaltase expression in adult rat small intestine. AB - Sucrase-isomaltase (SI) expression along the longitudinal and vertical axis of the small intestine was studied by sequentially isolating enterocytes from villus to crypt of rat proximal jejunum and distal ileum. Gradients of sucrase activity were observed with greatest activity occurring in jejunal and villus regions. Along the villus-to-crypt axis, gradients of SI mRNA abundance corresponded with activity. However, along the longitudinal axis no differences in SI mRNA levels were observed, thus not accounting for the observed 3-5-fold difference in SI activities between jejunum and ileum. Comparison of SI immunoprecipitates from jejunal and ileal mucosal scrapings showed significant differences in gel mobilities of the more mature forms, which did not appear to affect SI functional activities. When relative rates of de novo SI protein synthesis were compared, [35S]methionine incorporation into all SI forms was observed to be 3-5-fold greater in jejunum than in ileum at all time points. Because these results suggested differences in regional translational regulation, subcellular distribution of SI mRNA in jejunal and ileal epithelial cells was compared. A greater proportion of jejunal SI mRNA was found to be associated with membrane bound polyribosomes. We conclude 1) sucrase expression along the villus-to-crypt axis correlates with SI mRNA abundance, 2) post-translational processing of SI differ in ileum and jejunum, but appear not to determine SI expression, and 3) differences in translational processing in distal ileum and proximal jejunum may determine sucrase activity along the longitudinal axis of rat small intestine. PMID- 1939206 TI - Loss of intragenomic DNA repair heterogeneity with cellular differentiation. AB - The influence of terminal differentiation on UV-induced DNA damage and its repair in transcriptionally active and inactive genomic sequences was investigated using the murine 3T3-T proadipocyte cell culture system. Actively cycling 3T3-T cells terminally differentiate into adipocytes after exposure to media containing platelet-depleted human plasma. Suitable DNA fragments were analyzed from four genes: beta-actin, adenosine deaminase, dihydrofolate reductase, and lipoprotein lipase. As a result of 3T3-T cell differentiation, lipoprotein lipase and beta actin expression was modified, whereas adenosine deaminase and dihydrofolate reductase expression was not affected. A DNA fragment representing the transcriptionally inactive locus 70-38 was also evaluated. UV-induced cyclobutane pyrimidine dimers, detected as UV-specific endonuclease-sensitive sites, in each fragment increased linearly as a function of UV dose (0-20 J/m2) independently of gene expression or differentiation. Sequence-specific repair of dimers was measured in stem and terminally differentiated 3T3-T cells after UV irradiation (10 J/m2). For undifferentiated stem cells, the rate and extent of dimer repair was higher in the actively transcribed adenosine deaminase and dihydrofolate reductase genes than in the inactive lipoprotein lipase or 70-38 fragments, the greater difference being observed in the first 8 h post-UV irradiation. In contrast, similar dimer repair rates were found for each DNA fragment in terminally differentiated 3T3-T cells. These data suggest that cellular differentiation is accompanied by a loss of heterogeneity in intragenomic DNA repair. PMID- 1939207 TI - Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma. AB - A novel plasminogen-binding protein has been isolated from human plasma utilizing plasminogen-Sepharose affinity chromatography. This protein copurified with alpha 2 antiplasmin when the plasminogen affinity column was eluted with high concentrations of epsilon-aminocaproic acid (greater than 20 mM). Analysis by sodium dodecyl sulfate suggests this protein has an apparent Mr of 60,000. The amino-terminal amino acid sequence showed no similarity to other protein sequences. Based on the amino-terminal amino acid sequence, oligonucleotide probes were designed for polymerase chain reaction primers, and an approximately 1,800 base pair cDNA was isolated that encodes this Mr 60,000 protein. The deduced amino acid sequence reveals a primary translation product of 423 amino acids that is very similar to carboxypeptidase A and B and consists of a 22-amino acid signal peptide, a 92-amino acid activation peptide, and a 309-amino acid catalytic domain. This protein shows 44 and 40% similarity to rat procarboxypeptidase B and human mast cell procarboxypeptidase A, respectively. The residues critical for catalysis and zinc and substrate binding of carboxypeptidase A and B are conserved in the Mr 60,000 plasminogen-binding protein. The presence of aspartic acid at position 257 of the catalytic domain suggests that this protein is a basic carboxypeptidase. When activated by trypsin, it hydrolyzes carboxypeptidase B substrates, hippuryl-Arg and hippuryl Lys, but not carboxypeptidase A substrates, and it is inhibited by the specific carboxypeptidase B inhibitor (DL-5-guanidinoethyl)mercaptosuccinic acid. We propose that the Mr 60,000 plasminogen-binding protein isolated here is a novel human plasma carboxypeptidase B and that it be designated pCPB. PMID- 1939209 TI - Induction of expression of the alpha v beta 1 and alpha v beta 3 integrin heterodimers during retinoic acid-induced neuronal differentiation of murine embryonal carcinoma cells. AB - All-trans-retinoic acid, an endogenous morphogen, induced neuronal differentiation of P19 murine embryonal carcinoma cells. Peak differentiation, as judged by the elaboration of neuronal processes, occurred 8 days after exposure of the cells to 0.5 mM retinoic acid, a concentration known to induce neuronal differentiation. An examination of the expression of the extracellular matrix receptors, integrins, during this retinoic acid-induced differentiation period, demonstrated a specific and strong induction of expression of two polypeptides (130 and 115 kDa) immunoprecipitated with an anti-human vitronectin receptor antiserum. The expression of a 90-kDa polypeptide, also immunoprecipitating with this antiserum was induced as well, but to a much smaller extent. The expression of a 96-kDa polypeptide immunoprecipitated by this antiserum and present in the untreated cells was not induced by retinoic acid. The increase in the expression of these polypeptides paralleled the neuronal differentiation of the P19 embryonal carcinoma cells. The expression of these integrins was not induced in a variant of the P19 cells, P19RAC65, which are resistant to differentiation induction by retinoic acid. Utilizing integrin subunit-specific anti-cytoplasmic peptide antibodies together with immunoprecipitation and Western blot analysis, the 130- and 115-kDa polypeptides were identified as the integrin alpha v and beta 1 subunits, respectively. The 90-kDa polypeptide, also induced by retinoic acid, was identified as beta 3, whereas the identity of the uninduced 96-kDa polypeptide remains unclear as yet. Peptide map analysis of deglycosylated polypeptides demonstrated that the 90- and 96-kDa polypeptides are distinct proteins and that the 115-kDa polypeptides immunoprecipitated with either anti alpha v or anti-beta 1 antibodies are identical, further establishing that the 115-kDa polypeptide associating with alpha v is beta 1. The retinoic acid-induced expression of beta 1 occurred at the level of mRNA expression which also paralleled neuronal differentiation, but peaked slightly ahead of the cell surface expression of beta 1. The expression of other beta 1-associated alpha subunits was not induced by retinoic acid in these cells. These data demonstrate that retinoic acid strongly induces the expression of the integrin heterodimer alpha v beta 1 and also, to a smaller extent, the expression of alpha v beta 3. The retinoic acid-induced, high level surface expression of the alpha v beta 1 heterodimer is tightly correlated with the induction of neuronal differentiation by retinoic acid. This finding suggests an important role for the alpha v beta 1 heterodimer in the neuronal differentiation process. PMID- 1939208 TI - Transcriptional repression of the GLUT4 and C/EBP genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha. AB - Fully differentiated 3T3-L1 adipocytes were chronically exposed to 5 nM tumor necrosis factor-alpha (TNF). This resulted in the development of an insulin resistance based on the inability of insulin to stimulate hexose uptake. Western blot analysis for glucose transporter protein in isolated membrane fractions indicated a total depletion of GLUT4 protein (insulin-responsive glucose transporter) in cells chronically treated with TNF. Plasma membrane content of GLUT1 protein (growth-related glucose transporter) was similar in both control and TNF-treated cells; however, the GLUT1 content of the intracellular membrane compartment had decreased markedly after TNF treatment. Continuous exposure to TNF resulted in an 85-90% decrease in the mRNA content for both GLUT4 and 422 (aP2, a lipid binding protein) genes relative to age matched controls, whereas insulin receptor mRNA levels declined by at least 50%. This was preceded by a marked decrease in mRNA accumulation for C/EBP, a transcription factor proposed to control expression of both GLUT4 and 422. The specificity of these observations was demonstrated by the lack of an effect of the chronic TNF treatment on either beta-actin or lipoprotein lipase mRNA content. The decreased content of GLUT4 and C/EBP mRNA was judged to be regulated at least in part at the level of transcription, based on the results of transcription run-on assays. Thus, the lack of response to insulin appeared due to a suppression of GLUT4 expression as well as a decreased intracellular content of GLUT1. PMID- 1939210 TI - Meizothrombin formation during factor Xa-catalyzed prothrombin activation. Formation in a purified system and in plasma. AB - Meizothrombin and thrombin formation were quantitated during factor Xa-catalyzed activation of human prothrombin in reaction systems containing purified proteins and in plasma. In the purified system considerable amounts of meizothrombin accumulated when prothrombin was activated by factor Xa (with or without accessory components) under initial steady state conditions. The ratio of the rates of meizothrombin and thrombin formation was not influenced by variation of the pH, temperature, or ionic strength of the reaction medium. When 2 microM prothrombin was activated by the complete prothrombinase complex (factor Xa, factor Va, Ca2+, and phospholipid) 80-90% of the initially formed reaction product was meizothrombin. Lowering the prothrombin concentration from 2 to 0.03 microM caused a gradual decrease in the ratio of meizothrombin/thrombin formation from 5 to 0.6. When the phosphatidylserine content of the phospholipid vesicles was varied between 20 and 1 mol % and prothrombin activation was analyzed at 2 microM prothrombin the relative amount of meizothrombin formed decreased from 85 to 55%. With platelets, cephalin, or thromboplastin as procoagulant lipid, thrombin was the major reaction product and only 30-40% of the activation product was meizothrombin. We also analyzed complete time courses of prothrombin activation both with purified proteins and in plasma. In reaction systems with purified proteins substantial amounts of meizothrombin accumulated under a wide variety of experimental conditions. However, little or no meizothrombin was detected in plasma in which coagulation was initiated via the extrinsic pathway with thromboplastin or via the intrinsic pathway with kaolin plus phospholipid (cephalin, platelets, or phosphatidylserine-containing vesicles). Thus, thrombin was the only active prothrombin activation product that accumulated during ex vivo coagulation experiments in plasma. PMID- 1939211 TI - Bacterial expression and secretion of various single-chain Fv genes encoding proteins specific for a Salmonella serotype B O-antigen. AB - Active single-chain Fv molecules encoded by synthetic genes have been expressed and secreted to the periplasm of Escherichia coli using the ompA secretory signal. Four different constructs were developed to investigate the effects of peptide linker design and VL-VH orientation on expression, secretion, and binding to a Salmonella O-polysaccharide antigen. Peptide linker sequences derived from the elbow regions of the Fab molecule were used alone or in combination with the flexible (GGGGS)2 sequence. VL and VH domain order in the single chain molecules had a profound effect on the level of secretion but hardly influenced total expression levels, which were approximately 50 mg/liter, chiefly in the form of inclusion bodies. With VL in the NH2-terminal position, the amount of secreted product obtained was 2.4 mg/liter, but when VH occupied this position the yield was less than 5% of this value. Enzyme immunoassays of the four products showed domain order and linker sequence affected antigen binding by less than an order of magnitude. Attempts to express active Fv from dicistronic DNA were unsuccessful, but active Fv was obtained from single-chain Fv by enzymic cleavage at a site in the elbow linker peptide. The thermodynamic binding parameters of intact and cleaved single-chain Fvs determined by titration microcalorimetry were similar to those of bacterially produced Fab and mouse IgG. PMID- 1939212 TI - Characterization of estrogen-responsive mouse lactoferrin promoter. AB - Mouse lactoferrin is expressed in a variety of tissues under different types of control. To understand how molecular mechanisms govern the mode of lactoferrin expression, we isolated and characterized the 5'-flanking region of the lactoferrin gene. Several clones containing lactoferrin gene fragments were isolated from a mouse (129/J) genomic library including clone lambda J14, which contains a 7.5-kilobase pair 5'-flanking sequence. Sequence analysis of the region flanking the transcription initiation site revealed the following: a TATA like sequence, two CAAT boxes, three GC boxes including one within the first intron, an AP2 site, seven PU boxes, an AC-rich region, a B1 sequence, and an estrogen-responsive element consensus sequence over-lapping with a chicken ovalbumin upstream promoter-binding element. Footprinting analysis demonstrated that several regions, including the putative estrogen-responsive element region, in the 5'-flanking sequence were protected from DNase I digestion. Promoter fragments were cloned into a chloramphenicol acetyltransferase receptor plasmid to study functional activity. The mouse lactoferrin gene promoter was active in human endometrium carcinoma RL 95-2 cells and in rat glioma C6 cells. Multiple upstream elements modulated the basal transcriptional promoter activity. The transcription level directed by this minimal promoter was controlled by both positive (between -1739 and -922) and negative (between -2644 and -1739, and between -589 and -291) regulatory sequences. A tissue-specific regulatory sequence was critical for the establishment of lactoferrin expression in human endometrium carcinoma cells, but not in rat glioma cells located between -1739 and -922. Reporter plasmid 0.6 mL14-CAT, containing the estrogen-responsive element sequence, was estrogen-responsive in the presence of estrogen receptor in human endometrium carcinoma RL 95-2 cells. PMID- 1939213 TI - Negative regulatory elements in the human parathyroid hormone gene. AB - We have identified and characterized a pair of negative regulatory elements far upstream of the transcription start site of the human parathyroid hormone (hPTH) gene. Transfection of various types of cultured cells with a fusion plasmid containing 4.7 kilobase pairs of the 5'-flanking portion of the hPTH gene linked to the chloramphenicol acetyltransferase (CAT)-coding sequence generated only 10% of the CAT activity of a plasmid containing 684 base pairs of the 5'-flanking region of the hPTH gene. Deletion analyses reveal that there are at least two separate upstream DNA elements in the hPTH gene responsible for the negative regulation. We find that these cultured cells possess nuclear factors which specifically bind to several short DNA sequences within these elements and that these sequences can suppress transcription of the hPTH gene. PMID- 1939214 TI - Short chain collagens in sponges are encoded by a family of closely related genes. AB - Two previously described sponge cDNAs, EmC4 and C23, respectively encoding a short chain collagen and a fibrillar collagen, were used to characterize collagen gene families in a freshwater sponge. EmC4 detected several clones when used to screen a cDNA library. Two overlapping clones, EmC13 1 and 2, were sequenced and appeared highly homologous to EmC4. Contrarily to C23, EmC4 hybridized with 10-12 fragments of genomic DNA digested with restriction endonucleases and detected 10 times more positive clones than C23 when used to screen a genomic library. The genomic clone G41 contained two closely related genes, COLNF13, corresponding to EmC13 and COLNF6. Partial characterization of COLNF13 revealed two partial exons and four complete exons of 153, 219, 207, and 144 base pairs, with split glycine codons at their boundaries. The deduced encoded protein is a short chain collagen containing two uninterrupted collagenous domains of 66 and 171 amino acids and non-collagenous domains. A characterized 207-base pair exon of COLNF6 is 77% identical with the comparable COLNF13 exon. In situ hybridization using EmC4 cDNA and electron microscopy suggested that the cells expressing these genes were secreting spongin, a non-fibrillar, surface collagen of these sponges. PMID- 1939215 TI - Isolation and structural elucidation of a novel type of ganglioside, deaminated neuraminic acid (KDN)-containing glycosphingolipid, from rainbow trout sperm. The first example of the natural occurrence of KDN-ganglioside, (KDN)GM3. AB - Rainbow trout sperm contained almost exclusively monoanionic ganglioside fraction as a major acidic glycosphingolipid. Two monoacidic gangliosides were isolated and purified in this study and designated as sperm ganglioside 1 and 2 (sg-1 and sg-2). The two gangliosides, sg-1 and sg-2, contained the same neutral sugars, galactose and glucose in molar ratio of 1:1 and no GalNAc except for the presence of N-acetyl-neuraminic acid (NeuAc) in sg-1 and deaminated neuraminic acid (KDN; 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid) in sg-2. The complete structures of these gangliosides were determined by a combination of methylation analysis, fast atom bombardment mass spectrometry, 400-MHz one- and two-dimensional 1H nuclear magnetic resonance spectroscopy, fatty acid analysis, and endoglycoceramidase digestion NeuAc alpha 2----3Gal beta 1----4Glc beta 1----Cer sg-1 [(NeuAc)GM3] KDN alpha 2----3Gal beta 1----4Glc beta 1----Cer sg-2 [(KDN)GM3] where, for both sg-1 and sg-2, the ceramide moieties (Cer) were found to be made up of 4-sphingenine and mainly C16:0 fatty acid (palmitate; 95%) with a minor amount of C24:1 fatty acyl chain (nervonate, 5%). The structure of sg-2 is novel and represents the first example of a new class of gangliosides, i.e. KDN-gangliosides. PMID- 1939216 TI - Histone deacetylase is a component of the internal nuclear matrix. AB - In chicken immature erythrocytes, approximately 4% of the modifiable histone lysine sites participate in active acetylation. There are two categories of actively acetylated histone H4. Although both are acetylated at the same rate (t1/2 = 12 min), one is acetylated to the tetraacetylated form and is rapidly deacetylated (class 1), and the other is acetylated to mono- and diacetylated forms and is slowly deacetylated (class 2). We show that the chromatin distribution of the class 1 labeled tetraacetylated H4 species paralleled that of the transcriptionally active DNA sequences. For example, the chromatin fragments of the insoluble nuclear material contained 76% of the active DNA and 74% of the labeled tetraacetylated H4. Class 2 labeled acetylated H4 species were found in repressed chromatin and were enriched in active/competent gene-enriched chromatin fragments. The majority of the histone deacetylase activity (75-80%) was located with the insoluble residual nuclear material. Further, approximately 40-50% of the enzyme activity was associated with nuclear matrices prepared by two methods using high salt and intermediate/high salt extraction. Histone deacetylase was solubilized by extracting the nuclear matrices with high salt and 2 mercaptoethanol, a procedure that generates nuclear pore-lamina complexes. These results demonstrate that histone deacetylase is a component of the internal nuclear matrix. PMID- 1939217 TI - The role of von Willebrand factor multimers and propeptide cleavage in binding and stabilization of factor VIII. AB - von Willebrand factor (vWF) is a multimeric glycoprotein that promotes platelet aggregation and stabilizes coagulation factor VIII in the plasma. vWF is also required for the stable accumulation of recombinant factor VIII secreted from cells in a heterologous expression system. In this report, we show that vWF can promote the in vitro reconstitution of factor VIII activity from dissociated heavy and light chains of factor VIII, suggesting that vWF may act to promote stable assembly of factor VIII subunits at the site of secretion. The structural requirements for vWF propeptide cleavage and for vWF multimerization in its binding and stabilization of factor VIII was examined using specifically altered recombinant vWF. The mutant vWF molecules were also assayed for their function in ristocetin-induced platelet agglutination mediated through the platelet receptor GPIb. Deletion of the vWF propeptide produced a dimeric vWF molecule that failed to mediate platelet agglutination, suggesting that multimerization is required for vWF to attain functional GPIb binding. This mature dimeric form of vWF, however, was fully capable of binding to and supporting stable secretion of factor VIII. A vWF mutant with an altered propeptide cleavage site formed large multimers of uncleaved pro-vWF that functioned in platelet agglutination. However, this noncleavage mutant neither bound to or supported stable accumulation of factor VIII. Analysis of the vWF propeptide, expressed independently, demonstrated that it could not bind factor VIII or stabilize its secretion. These results show that the dimeric mature vWF subunit is sufficient to bind and stabilize factor VIII and that the presence of uncleaved vWF propeptide inhibits both factor VIII binding and stabilization. PMID- 1939218 TI - Identification of a negative regulatory region 5' of the human apolipoprotein B promoter. AB - We have identified a negative regulatory region between positions -1802 and -3211 of the human apolipoprotein B gene that reduces expression of the gene. This "reducer" effect was detected in transient transfection experiments performed with hepatic (HepG2 and Hep3B) cells as well as intestinal (CaCo-2) cells. It appears to be specific for the apolipoprotein B promoter because it did not affect expression from the heterologous thymidine kinase promoter. This reducer segment operated in the presence or absence of the transcriptional enhancer from the second intron of the apolipoprotein B gene, suggesting that the protein factors involved in the enhancer and reducer effect can interact with the transcriptional machinery independently of each other. Deletion experiments further localized the positions of the negative regulatory elements in HepG2 cells: sequences between positions -2738 and -2470 together with those from -2118 to -1802 are required for the reducer activity. DNase I footprinting of these two reducer DNA segments identified several DNA sequences that are bound by nuclear proteins from HepG2 cells. Analysis of the nucleotide sequences within these footprints demonstrated a high degree of similarity with sequences within negative regulatory regions of other genes. PMID- 1939219 TI - Zinc-binding subunits of yeast RNA polymerases. AB - The zinc-binding subunits of yeast RNA polymerase A(I) and B(II) have been identified by a zinc-blotting technique. The two largest subunits of each enzyme (A190, A135, B220, and B150), as well as A12.2, A10, B44.5, B12.6, and B10, bind 65Zn(II). Predicted zinc-binding motifs have been noted in the NH2-terminal part of B220 and the COOH-terminal region of B150 subunits. Subdomains encompassing these motifs have been overproduced as MalE-fusion proteins and shown to retain zinc binding activity. Site-directed mutagenesis in the predicted metal-binding domain of B150 demonstrated its role in zinc binding. Mutations of cysteine residues C1163, C1166, C1182, and C1185 affected 65Zn2+ binding in vitro and caused a lethal or thermosensitive phenotype for growth. The ability to bind zinc is not sufficient for function since mutations in vicinal residues not affecting zinc binding were either lethal or thermosensitive. The role of zinc in RNA polymerase structure and function is discussed in the light of the present results. PMID- 1939220 TI - Genetic regulation of malic enzyme activity in the mouse. AB - Cytosolic malic enzyme catalyzes the NADP(+)-dependent oxidative decarboxylation of malate to pyruvate and CO2. Additionally, this enzyme produces large amounts of reducing equivalents (NADPH) required for de novo fatty acid synthesis and provides a precursor for oxaloacetate replacement in the mitochondria. Malic enzyme is considered a key lipogenic enzyme and changes in enzyme activity parallel changes in the lipogenic rate. As would be expected, the activity of malic enzyme responds to a variety of dietary and hormonal factors acting mainly on the rate of enzyme synthesis. In the mouse, the structural locus for malic enzyme (Mod-1) is located on chromosome 9. Two alleles reflecting differences in electrophoretic mobility have been identified. This report demonstrates that the amount of hepatic malic enzyme activity is strain-dependent and is regulated by a malic enzyme regulator locus (Mod1r) located on the proximal end of chromosome 12. Two alleles have been identified: Mod1ra, conferring high enzyme activity (C57BL/6J), and Mod1rb, conferring low enzyme activity (C57BL/KsJ). Biochemical studies have demonstrated differences in the apparent Km and Vmax and in specific activity on purification and immunoprecipitation, features that suggest changes in enzyme structure even though no differences were observed by electrophoresis and isoelectric focusing. These combined data suggest that differences in both enzyme quantity and structure may be involved in the genetic regulation of malic enzyme activity in mice. PMID- 1939221 TI - Phorbol ester stimulation of protein kinase C activity and ribosomal DNA transcription. Role in hypertrophic growth of cultured cardiomyocytes. AB - The mechanism by which phorbol esters induce hypertrophic growth of cardiomyocytes was investigated. Control and 4 alpha-phorbol 12,13-didecanoate treated myocytes demonstrated a slow rate of growth as measured by the protein/DNA ratio and cell area. In contrast, treatment with phorbol 12-myristate 13-acetate (PMA) stimulated protein accumulation by 34%, while cell area was increased by 68% over control myocytes after 72 h. RNA content in PMA-treated myocytes was 33% higher than in control cells and 4 alpha-phorbol 12,13 didecanoate-treated cells after 72 h. Membrane-associated protein kinase C activity was transiently increased after PMA treatment but returned to normal by 48 h. Cytosolic protein kinase C activity was not significantly altered by PMA. Membrane-associated and cytosolic protein kinase C activities were not altered by 4 alpha-phorbol 12,13-didecanoate. Protein kinase C activity, RNA polymerase I activity, and the transcriptional rate of ribosomal DNA (rDNA) were increased in nuclei isolated from PMA-treated cells. However, consistent with a high rate of processing of pre-ribosomal RNA (pre-rRNA), the pool size of pre-rRNA relative to the 28 S rRNA was unaltered by PMA treatment. These data demonstrated that PMA induced hypertrophic growth of cardiomyocytes was due to an increase in the capacity for protein synthesis (rRNA), and suggest that this results from protein kinase C mediated increase in the rate of transcription of rDNA. PMID- 1939222 TI - Biosynthesis of delta-aminolevulinic acid and the regulation of heme formation by immature erythroid cells in man. AB - Heme formation in the erythron is subject to end product regulation by negative feedback, but the exact point of metabolic control in human erythroid cells is unknown. To investigate the mode of action of heme on its own formation, the effects of micromolar concentrations of hemin on de novo synthesis of protoporphyrin IX and delta-aminolevulinate (delta-ALA) by intact human reticulocytes were examined in the presence of 1 mM alpha,alpha'-bipyridyl and 200 microM 4,6-dioxoheptanoate to block their further conversion by ferrochelatase or delta-ALA dehydrase, respectively. At final concentrations (25 40 microM), hemin, which is known to reduce incorporation of [2-14C]glycine into cellular heme, significantly inhibited formation of protoporphyrin IX and total delta-aminolevulinate in situ by these cells. Since synthesis of the first committed precursor, delta-aminolevulinate, as well as protoporphyrin (which is derived from it) were diminished, the effects of hemin on delta-aminolevulinate synthase (EC 2.3.1.37) were studied. Hemin, at concentrations up to 40 microM, had no direct effect on enzymatic activity, as measured with [5-14C] alpha ketoglutarate (in hypotonically lysed cells) or [1,4-14C]succinyl coenzyme A (in deoxycholate lysates), even after preincubation. However, when intact human reticulocytes were incubated with hemin before assay for delta-ALA synthase, there was a rapid, concentration-dependent reduction in enzymatic activity (mean 42 and 23% inhibition after 60 min for these two substrates, respectively). Hemin had no effect on steady-state levels of delta-ALA synthase mRNA, as determined by Northern blot hybridization using an erythroid-specific human cDNA probe. Thus, a mechanism for inducing feedback inhibition of the tetrapyrrole pathway exists in human erythroid cells. It controls formation of the first committed precursor of protoporphyrin IX, delta-aminolevulinate, and hence regulates heme biosynthesis by limiting the availability of the porphyrin, rather than the metal substrate for the ferrochelatase reaction. Hemin interacts with constituents of the intact reticulocyte significantly to reduce delta-aminolevulinic acid synthase activity by an indirect cellular process that does not influence the abundance of erythroid-specific synthase mRNA but may either inhibit its ribosomal translation in an unknown manner or promote degradation of the enzyme itself by specific proteolysis. PMID- 1939223 TI - The microtubule-associated protein tau forms a triple-stranded left-hand helical polymer. AB - High resolution transmission electron microscopy (TEM) has shown that bovine tau are 2.1 +/- 0.2-nm diameter filaments which are triple-stranded left-hand helical structures composed of three 1.0 +/- 0.2-nm strands. The reported amino acid sequence of human and bovine tau have been computer processed to predict secondary structure. Within the constraints imposed by the images, the secondary structure models and other structural information have been used to calculate tau's maximum and minimum length. The length calculations and secondary structure form the basis for image interpretation. This work indicates that each approximately 1.0-nm strand is a tau polypeptide chain and that the approximately 2.1-nm filament is composed of three separate tau chains (tau3). Bovine tau length measurements indicate that tau trimer filaments are generally longer than a fully extended tau monomer. These measurements indicate that each trimer, tau3, is joined with other trimers to form long tau polymers, (tau3)n. An inverse temperature transition has been found in the circular dichroism spectrum of tau indicating that its structure is less ordered below 20 degrees C and more ordered at 37 degrees C. The implications of this phenomenon with respect to tau's temperature-dependent ability to reconstitute microtubules is discussed and a mechanism for the possible abnormal aggregation of tau into neurofibrillary tangles in Alzheimer's disease is proposed. PMID- 1939224 TI - Phosphorylation of Gz in human platelets. Selectivity and site of modification. AB - We have demonstrated previously that the G protein alpha subunit Gz alpha (or Gx alpha) in human platelets is subject to phosphorylation by agents that activate protein kinase C, including phorbol 12-myristate 13-acetate, thrombin, and the thromboxane A2 analog U46619. We examine here the site and selectivity of phosphorylation both in vitro using recombinant G protein alpha subunits and in situ using permeabilized and intact platelets. Protein kinase C catalyzes the rapid and nearly stoichiometric phosphorylation of recombinant Gz alpha, with the modification occurring preferentially for the GDP-bound form of the subunit. Under the same conditions, phosphorylation of recombinant Gi alpha 1, Gi alpha 2, Gi alpha 3, Gs alpha-S, Gs alpha-L, and Go alpha 1 was minimal. Phosphorylation of both rGz alpha and platelet Gz alpha occurs at a serine residue near the amino terminus. This conclusion is supported by phosphoamino acid analysis and the incorporation of radiolabel from [gamma-32P]ATP into the amino-terminal CNBr peptide (residues 2-53 of the encoded protein). One of the antisera used in this study (6354, directed toward residues 24-33) recognizes only the nonphosphorylated form of Gz alpha, providing strong evidence that Ser25 or Ser27 is the site of phosphorylation. Results obtained with 6354 also suggest that phorbol ester-promoted phosphorylation of Gz alpha approaches 1 mol of phosphate per mol of subunit in permeabilized platelets. PMID- 1939225 TI - Evaluation of the role of conserved His and Met residues among lipoxygenases by site-directed mutagenesis of recombinant human 5-lipoxygenase. AB - The 5-, 12-, and 15-lipoxygenases contain a highly conserved sequence of the form His-(X)4-His-(X)4-His-(X)17-His-(X)8-His which represents a potential binding site for non heme iron to the protein. The importance of selected amino acids within this His cluster for the activity of human 5-lipoxygenase was investigated by site-directed mutagenesis using bacteria and insect cells expression systems. After single mutation of each of the 5 His residues at positions 363, 368, 373, 391, and 400 by Ser, Cys, or Lys, measurable levels of 5-lipoxygenase activity could be recovered in Escherichia coli only for the Ser363 and Cys363 mutants, with most amino acid substitutions causing a decrease in the levels of expression of the soluble protein. In contrast, 25-80% of soluble 5-lipoxygenase activity was recovered after the replacement of several of the hydrophobic amino acids in this region: Tyr384 by Ser or Phe; Phe394 by Trp and Val375 by Ala. Met436 could be replaced by Leu with little effect on 5-lipoxygenase activity or turnover inactivation half-time. High levels of mutant 5-lipoxygenases containing a Ser residue instead of His at each of the five positions were also expressed in Spodoptera frugiperda (Sf9) cells infected with recombinant baculovirus. The specific activity (58-75% of control) and the reaction time course of the Ser363, Ser391, and Ser400 mutants were comparable with that of native 5-lipoxygenase whereas inactive proteins were obtained for the Ser368 and Ser373 mutants. These results show that His368 and His373 residues are important for 5-lipoxygenase activity and that the other conserved His363, His391, His400, and Met436 residues are not crucial for the catalytic cycle or for the mechanism of self-inactivation of 5-lipoxygenase. PMID- 1939226 TI - Lysine residues 165 and 166 are essential for the cofactor function of tissue factor. AB - Tissue factor, a 45-kilodalton membrane glycoprotein, is an essential cofactor for the plasma serine protease factor VII which activates factor X in the first step of the extrinsic coagulation cascade. Two adjacent lysine residues (numbers 165 and 166) were identified in the extracytoplasmic domain of tissue factor that are crucial for function. Site-directed mutagenesis of both lysines to alanines results in complete loss of activity. Mutation of either lysine alone results in a molecule which is much more sensitive to the phospholipid composition of the activating surface than the wild-type molecule. It is postulated that interactions between the extracytoplasmic domain of tissue factor and the membrane surface are necessary for bound factor VII or VIIa to assume a conformation capable of efficient catalysis. PMID- 1939227 TI - Conotoxins. PMID- 1939228 TI - Direct injection of hepatitis B virus DNA into liver induced hepatitis in adult rats. AB - Hepatitis B virus (HBV) surface antigen (HBsAg) genes were injected directly into the liver of adult rats with non-histone chromosomal protein high mobility group 1 by the hemagglutinating B virus of Japan (Sendai virus)-liposome method (Kato, K., Nakanishi, M., Kaneda, Y., Uchida, T., and Okada, Y. (1991) J. Biol. Chem. 266, 3361-3364). Immunohistochemical analysis showed that HBV surface antigen was expressed by the hepatocytes in vivo. On successive injections of the HBsAg genes, the antibody to HBV surface polypeptides was produced in the rats, and characteristic pathological changes of lymphocytic focal necrosis and denaturation of hepatic cells were observed in the liver of all the rats. We conclude that hepatitis is caused by the direct injection of HBsAg genes. PMID- 1939229 TI - Creation of "super" glucocorticoid receptors by point mutations in the steroid binding domain. AB - Almost all modifications of the steroid binding domain of glucocorticoid receptors are known to cause a reduction or loss of steroid binding activity. Nonetheless, we now report that mutations of cysteine 656 of the rat receptor, which was previously suspected to be a crucial amino acid for the binding process, have produced "super" receptors. These receptors displayed an increased affinity for glucocorticoid steroids and a decreased relative affinity for cross reacting steroids such as progesterone and aldosterone. The increased in vitro affinity of the super receptors was maintained in a whole cell bioassay. These results indicate that additional modifications of the glucocorticoid receptor, and probably the other steroid receptors, may further increase the binding affinity and/or specificity. PMID- 1939230 TI - Proteolytic cleavage of ricin A chain in endosomal vesicles. Evidence for the action of endosomal proteases at both neutral and acidic pH. AB - Macrophages actively internalize macromolecules into endosomal vesicles containing proteases. The plant toxin, ricin A chain delivered into this pathway by receptor-mediated endocytosis, was found to be exquisitely sensitive to cleavage by these proteases. Proteolytic fragments of ricin A chain were generated within cells as early as 2-3 min after internalization. Toxin proteolysis was initiated in early endosomal vesicles, and transport to lysosomes was not required. As endosomes transit the cell, their lumenal pH drops from neutral to acidic. Previous studies in macrophages had suggested that endosomal proteolysis is dependent on vesicle acidification. Isolated endosomal vesicles containing ricin A chain catalyzed the cleavage of this protein in vitro; however, proteolysis was observed at both neutral and acidic pH. Experiments using isolated endosomes demonstrated that both cysteine and aspartyl proteases were responsible for the cleavage of ricin A chain. The cysteine protease, cathepsin B, catalyzed toxin proteolysis in endosomes between pH 4.5 and 7.0 while aspartyl protease activity was maximal below pH 5.5. Radiolabeling the lumenal contents of macrophage endosomes confirmed that both the cysteine protease, cathepsin B, and the aspartyl protease, cathepsin D, were present in these vesicles. These proteases were not present on the plasma membrane but were found in early endosomes indicating they are derived from an intracellular source. The presence of proteases with different pH optima in early endosomes suggests that processing in these vesicles may be regulated by changes in endosomal pH. This result represents an important difference in protein processing in endosomes versus lysosomes and provides new insights into the function of endosomal proteases. PMID- 1939231 TI - Chemical and transient state kinetic studies on the formation and decomposition of horseradish peroxidase compounds XI and XII. AB - Previous studies on the chlorination reaction catalyzed by horseradish peroxidase using chlorite as the source of chlorine detected the formation of a chlorinating intermediate that was termed Compound X (Shahangian, S., and Hager, L.P. (1982) J. Biol. Chem. 257, 11529-11533). These studies indicated that at pH 10.7, the optical absorption spectrum of Compound X was similar to the spectrum of horseradish peroxidase Compound II. Compound X was shown to be quite stable at alkaline pH values. This study was undertaken to examine the relationship between the oxidation state of the iron protoporphyrin IX heme prosthetic group in Compound X and the chemistry of the halogenating intermediate. The experimental results show that the optical absorption properties and the oxidation state of the heme prosthetic group in horseradish peroxidase are not directly related to the presence of the activated chlorine atom in the intermediate. The oxyferryl porphyrin heme group in alkaline Compound X can be reduced to a ferric heme species that still retains the activated chlorine atom. Furthermore, the reaction of chlorite with horseradish peroxidase at acidic pH leads to the secondary formation of a green intermediate that has the spectral properties of horseradish peroxidase Compound I (Theorell, H. (1941) Enzymologia 10, 250-252). The green intermediate also retains the activated chlorine atom. By analogy to peroxidase Compound I chemistry, the heme prosthetic group in the green chlorinating intermediate must be an oxyferryl porphyrin pi-cation radical species (Roberts, J. E., Hoffman, B. M., Rutter, R. J., and Hager, L. P. (1981) J. Am. Chem. Soc. 103, 7654-7656). To be consistent with traditional peroxidase nomenclature, the red alkaline form of Compound X has been renamed Compound XII, and the green acidic form has been named Compound XI. The transfer of chlorine from the chlorinating intermediate to an acceptor molecule follows an electrophilic (rather than a free radical) path. A mechanism for the reaction is proposed in which the activated chlorine atom is bonded to a heteroatom on an active-site amino acid side chain. Transient state kinetic studies show that the initial intermediate, Compound XII, is formed in a very fast reaction. The second-order rate constant for the formation of Compound XII is approximately 1.1 x 10(7) M-1 s-1. The rate of formation of Compound XII is strongly pH-dependent. At pH 9, the second-order rate constant for the formation of Compound XII drops to 1.5 M-1 s 1. At acidic pH values, Compound XII undergoes a spontaneous first-order decay to yield Compound XI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1939232 TI - Different interactions of Cro repressor dimer with the left and right halves of OR3 operator DNA. AB - lambda Cro repressor protein is titrated with two half-operator DNA duplexes comprising the right and left halves of the major binding site on phage lambda DNA, the OR3 operator. The comparison of binding strengths and the conformation of Cro repressor in the two protein-DNA complexes shows that base pair differences between the two halves of the OR3 operator affect the binding of Cro repressor protein. Some 1H NMR resonances are assigned for both protein and DNA in the Cro-operator DNA complexes which are then used to highlight differences between Cro right half and Cro left half protein-operator DNA interactions. These differences are compared to the asymmetry found in the lambda C1 repressor operator DNA complex. Mechanisms for the recognition of the Cro transcriptional regulatory protein have considered only interactions between a single Cro monomer and a consensus half-operator site with the assumption that the interactions in the remaining half-site are related by the 2-fold symmetry of the complex. A revised model is suggested that allows asymmetry in the two halves of the protein DNA complex. Methods are proposed to avoid problems in the general use of 1H NMR spectroscopy to study protein-DNA interaction such as intermediate exchange behavior and sample aggregation. PMID- 1939234 TI - Catalytic and regulatory properties of native and chymotrypsin-treated pyridoxine 5-phosphate oxidase. AB - Brain pyridoxine-5-P oxidase is activated by the tryptophan metabolites 3 hydroxyanthranilate and 3-hydroxykynurenine. 3-Hydroxyanthranilate at concentrations of 0.03 mM relieves the inhibition elicited by accumulation of the substrate pyridoxine-5-P (Ki = 60 microM). The results of fluorometric measurements indicate that four molecules of 3-hydroxyanthranilate bind to the dimeric enzyme (56 kDa) with an association constant of 5.5 x 10(4) M-1. Differential spectral measurements failed to detect any direct interaction between the cofactor FMN and the effector 3-hydroxyanthranilate. These results are consistent with the hypothesis that the effector molecules bind to sites of the dimeric protein distinct from the cofactor site. Limited chymotrypsin digestion of pyridoxine-5-P oxidase yields catalytically active species that are no longer susceptible to activation by 3-hydroxykynurenine. A polypeptide of 16 kDa containing FMN and endowed with full catalytic activity was isolated by ion exchange chromatography. It is postulated that the structural domain associated with catalytic activity composes approximately one-half of the molecular mass of pyridoxine-5-P oxidase (28 kDa), whereas the remaining portion of the macromolecule contains regulatory binding sites. PMID- 1939233 TI - Monoclonal antibodies to Escherichia coli ribosomal proteins L9 and L10. Effects on ribosome function and localization of L9 on the surface of the 50 S ribosomal subunit. AB - Monoclonal antibodies against Escherichia coli ribosomal proteins L9 and L10 were obtained and their specificity confirmed by Western blot analysis of total ribosomal protein. This was particularly important for the L9 antibody, since the immunizing antigen mixture contained predominantly L11. Each antibody recognized both 70 S ribosomes and 50 S subunits. Affinity-purified antibodies were tested for their effect on in vitro assays of ribosome function. Anti-L10 and anti-L9 inhibited poly(U)-directed polyphenylalanine synthesis almost completely. The antibodies had no effect on subunit association or dissociation and neither antibody inhibited peptidyltransferase activity. Both antibodies inhibited the binding of the ternary complex that consisted of aminoacyl-tRNA, guanylyl beta, gamma-methylenediphosphonate, and elongation factor Tu, and the binding of elongation factor G to the ribosome. The intact antibodies were more potent inhibitors than the Fab fragments. In contrast to the previously established location of L10 at the base of the L7/L12 stalk near the factor-binding site, the site of anti-L9 binding to 50 S subunits was shown by immune electron microscopy to be on the L1 lateral protuberance opposite the L7/L12 stalk as viewed in the quasisymmetric projection. The inhibition of factor binding by both antibodies, although consistent with established properties of L10 in the ribosome, suggests a long range effect on subunit structure that is triggered by the binding of anti L9. PMID- 1939235 TI - Glycine reductase protein C. Properties and characterization of its role in the reductive cleavage of Se-carboxymethyl-selenoprotein A. AB - The clostridial glycine reductase complex catalyzes the reductive deamination of glycine in an energy-conserving process that results in the esterification of orthophosphate. The complex consists of three protein components: selenoprotein A; protein B, a carbonyl group protein; and protein C, a sulfhydryl protein. The protein C component also catalyzes the arsenate-dependent decomposition of acetyl phosphate. Reaction of protein C with iodoacetate inhibits its ability to decompose acetyl phosphate, but this inactivation of the enzyme by alkylation is prevented in the presence of the substrate indicating the formation of an unreactive enzyme-bound acetylthiol ester. The Se-carboxy-methylselenocysteine residue of the selenoprotein A component of glycine reductase was generated by selective alkylation of the ionized selenol group at pH 6 with [14C]bromoacetate. Using this pure alkylated selenoprotein A as substrate, it was shown that protein C catalyzes the conversion of the [14C]carboxymethyl group, in selenoether linkage to protein A, to [14C]acetate in the presence of arsenate, dithiothreitol, and Mg2+. A procedure using hydrophobic chromatographic matrices was developed for the large scale isolation of protein C, and a number of the properties of the enzyme were determined. PMID- 1939236 TI - The synergistic inhibition of Escherichia coli aspartate carbamoyltransferase by UTP in the presence of CTP is due to the binding of UTP to the low affinity CTP sites. AB - Escherichia coli aspartate carbamoyltransferase controls pyrimidine biosynthesis by feedback inhibition involving both CTP and UTP, although UTP only inhibits the enzyme in the presence of CTP (Wild, J. R., Loughrey-Chen, S. J., and Corder, T. S. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 46-50). The mechanism by which the enzyme can discriminate between these two pyrimidines is unknown, as well as where UTP binds and its mode of action. A mutant version of the enzyme with a single amino acid substitution in the regulatory site (Asp-19----Ala) causes loss of the synergistic inhibition of UTP in the presence of CTP, and furthermore, this enzyme is inhibited by UTP alone. Analysis of CTP binding to the mutant enzyme reveals that UTP can bind to the mutant enzyme in the absence of CTP but not in its presence. This is completely opposite to the wild-type enzyme in which case UTP only exhibits significant binding in the presence of CTP. Further analysis of the binding data for the wild-type enzyme reveals that, in the presence of UTP, CTP only binds to three sites, although CTP binds to six sites, three with high affinity and three with low affinity in the absence of UTP. Parallel UTP binding experiments in the presence of CTP suggest that UTP binds to the three weak CTP sites. The Asp-19----Ala substitution prevents UTP binding in the presence of CTP and allows UTP to bind and inhibit the enzyme in the absence of CTP. Since the x-ray data indicate no specific interactions between the amino group of cytosine and amino acid side chains in the regulatory binding site, the discrimination between UTP and CTP by the wild-type enzyme must be due to subtle differences in the binding sites rather than direct side chain contacts. PMID- 1939237 TI - Identification of substrate recognition determinants for human ERK1 and ERK2 protein kinases. AB - Two epidermal growth factor-stimulated protein kinases that correspond to ERK1 and ERK2 have been purified from human epidermoid carcinoma cells (Northwood, I. C., Gonzalez, F. A., Wartmann, M., Raden, D. L., and Davis, R. J. (1991) J. Biol. Chem. 266, 15266-15276). A consensus primary sequence for substrates of ERK1 has been identified as -Pro-Leu-Ser/Thr-Pro- (Alvarez, E., Northwood, I. C., Gonzalez, F. A., Latour, D. A., Seth, A., Abate, C., Curran, T., and Davis, R. J. (1991) J. Biol. Chem. 266, 15277-15285). However, the structural determinants for substrate recognition are not understood. We performed a systematic analysis of the effect of point mutations in the primary sequence of peptide substrates on the rate of phosphorylation by ERK1 and ERK2. The results of this investigation demonstrate that the substrate specificities of the ERK1 and ERK2 protein kinases are very similar. We propose that the primary sequence of substrates for ERK1 and ERK2 protein kinases can be generalized as -Pro-Xaan-Ser/Thr-Pro- (where Xaa is a neutral or basic amino acid and n = 1 or 2). PMID- 1939238 TI - Mitosis-specific phosphorylation of myosin light chain kinase. AB - Cell cytosol preparations from mitotic HeLa cells exhibit a kinase activity that phosphorylates myosin light chain kinase (MLCK). This MLCK kinase activity is apparently distinct from the known MLCK kinases, including cAMP-dependent protein kinase, cGMP-dependent protein kinase, Ca(2+)-activated phospholipid-dependent protein kinase, or Ca(2+)-calmodulin-dependent protein kinase II, based on the following criteria. First, the MLCK kinase activity of mitotic cells does not respond to a variety of characteristic activators or inhibitors of these known kinases. Second, one- and two-dimensional peptide maps have revealed that the site of phosphorylation by the MLCK kinase of mitotic cells differs from those by these known kinases. The mitotic MLCK kinase phosphorylates MLCK at a threonine residue at a ratio of up to 1 mol of phosphate/mol of chicken gizzard MLCK. The MLCK kinase is mitosis-specific because mitotic cell extracts show much higher phosphorylation activity than nonmitotic cell extracts. PMID- 1939239 TI - Intrahepatic conversion of a glutathione conjugate to its mercapturic acid. Metabolism of 1-chloro-2,4-dinitrobenzene in isolated perfused rat and guinea pig livers. AB - Because of the low hepatic activity of gamma-glutamyl-transferase in the rat, the liver is generally considered to play only a minor role in the degradation of glutathione conjugates, a limiting step in mercapturic acid formation. Recent findings indicate, however, that the liver has a prominent role in glutathione catabolism, particularly in species other than rat. To examine the contributions of liver to mercapturic acid biosynthesis, mercapturate formation was compared in isolated perfused livers from rats and guinea pigs dosed with either 0.3 or 3.0 mumol of 1-chloro-2,4-dinitrobenzene (CDNB). Chemically synthesized glutathione conjugate, mercapturic acid, and intermediary metabolites of CDNB were used as standards in the high performance liquid chromatography analysis of bile and perfusate samples. Biliary excretion accounted for almost all of the recovered metabolites. A marked species difference was observed in the pattern of CDNB metabolism. Rat livers dosed with 0.3 mumol of CDNB excreted 55% of total biliary metabolites as the glutathione conjugate and 8.2% as the mercapturic acid, whereas guinea pig livers excreted only 4.8% as the glutathione conjugate and 47% as the mercapturate. Mercapturic formation was also dose-dependent, with a larger fraction formed at the 0.3- versus the 3.0-mumol dose (8.2 versus 3.7% in the rat; 47 versus 19% in the guinea pig). Hepatic conversion of the glutathione conjugate to the mercapturic acid was markedly inhibited in both species after retrograde intrabiliary infusion of acivicin, an inhibitor of gamma glutamyltransferase activity. These findings provide direct evidence for intrahepatic biosynthesis of mercapturic acids. Thus, glutathione conjugates synthesized within hepatocytes are secreted into bile and broken down to cysteine conjugates; the latter are then presumably reabsorbed by the liver, N-acetylated to form the mercapturic acid and re-excreted into bile. PMID- 1939240 TI - Biochemical evidence for a third chain of the interleukin-2 receptor. AB - Two receptor proteins that specifically bind interleukin-2 (IL-2) have been identified previously. The L (Tac or alpha) chain can bind IL-2 with a Kd value of 10 nM (low affinity). Although the H (beta) chain expressed on lymphocytes can bind IL-2 with a Kd value of 1 nM (intermediate affinity), transfected fibroblasts expressing the H chain cannot bind IL-2, suggesting the involvement of other lymphocyte-specific factors for the function of the H chain. To obtain direct evidence for the presence of a third component of the IL-2 receptor, we examined the IL-2 binding activity of detergent-solubilized cell membrane preparations. We found that lysates of transfected Cos7 cells expressing H chains can bind IL-2 when mixed with lysates from lymphocytes that cannot bind IL-2. Chemical cross-linking of 125I-IL-2-bound lysate mixture and subsequent immunoprecipitation with a noncompetitive anti-H chain antibody gave rise to two 125I-IL-2-bound proteins, a 56-kDa protein (p56) and the H chain, although neither the H chain nor p56 alone is able to bind IL-2. These results indicate that p56 is the IL-2 receptor third chain that is required for IL-2 binding to the H chain. A similar lysate mixing experiment also showed that p56 is involved in IL-2 binding to the high affinity IL-2 receptor by forming the quaternary complex of IL-2, p56, L chain, and H chain. PMID- 1939242 TI - NAD(+)-dependent isocitrate dehydrogenase. Cloning, nucleotide sequence, and disruption of the IDH2 gene from Saccharomyces cerevisiae. AB - NAD(+)-dependent isocitrate dehydrogenase from Saccharomyces cerevisiae is composed of two nonidentical subunits, designated IDH1 (Mr approximately 40,000) and IDH2 (Mr approximately 39,000). We have isolated and characterized a yeast genomic clone containing the IDH2 gene. The amino acid sequence deduced from the gene indicates that IDH2 is synthesized as a precursor of 369 amino acids (Mr 39,694) and is processed upon mitochondrial import to yield a mature protein of 354 amino acids (Mr 37,755). Amino acid sequence comparison between S. cerevisiae IDH2 and S. cerevisiae NADP(+)-dependent isocitrate dehydrogenase shows no significant sequence identity, whereas comparison of IDH2 and Escherichia coli NADP(+)-dependent isocitrate dehydrogenase reveals a 33% sequence identity. To confirm the identity of the IDH2 gene and examine the relationship between IDH1 and IDH2, the IDH2 gene was disrupted by genomic replacement in a haploid yeast strain. The disruption strain expressed no detectable IDH2, as determined by Western blot analysis, and was found to lack NAD(+)-dependent isocitrate dehydrogenase activity, indicating that IDH2 is essential for a functional enzyme. Overexpression of IDH2, however, did not result in increased NAD(+) dependent isocitrate dehydrogenase activity, suggesting that both IDH1 and IDH2 subunits are required for catalytic activity. The disruption strain was unable to utilize acetate as a carbon source and exhibited a 2-fold slower growth rate than wild type strains on glycerol or lactate. This growth phenotype is consistent with NAD(+)-dependent isocitrate dehydrogenase performing an essential role in the oxidative function of the citric acid cycle. PMID- 1939241 TI - Alteration of channel activities and gating by mutations of slow ISK potassium channel. AB - ISK is a small membrane protein consisting of 129-130 amino acid residues with a single putative transmembrane domain and induces a very slow voltage-dependent K+ channel activity in the Xenopus oocyte expression system. We investigated the nature and structure-function relation of ISK by examining the effects of various mutations of ISK on the K+ channel activities measured in Xenopus oocytes. Deletion and truncation of the ISK protein indicated that the 63-amino acid sequence covering a transmembrane domain is sufficient for eliciting a K+ channel activity characteristic of ISK. Amino acid substitutions at a total of 31 positions within and surrounding the transmembrane domain caused different effects on the channel activity. A channel activity was enhanced by substitution of leucine with isoleucine at position 52 within the transmembrane domain, and the kinetic analysis of this mutation indicated that the enhancement of the channel activity is due to an alteration of a gating property of the ISK protein and thus supported the view that ISK forms an integral part of the K+ channel itself. The substitutions at many positions of the membrane-following region produced drastic reduction of the channel activity, and this is in marked contrast to the lack of effects of amino acid substitutions at the membrane preceding region. Thus, the cytoplasmic portion immediately following the transmembrane domain plays a crucial role in inducing the channel activity of ISK. PMID- 1939243 TI - Characterization of mutations in oligomerization domain of Lac repressor protein. AB - A series of mutant lac repressor proteins at positions 281 or 282 was isolated for detailed characterization. Although Cys281 modification by sulfhydryl reagents abrogates pH effects on inducer binding and diminishes operator binding (Daly, T. J., Olson, J. S., and Matthews, K. S. (1986) Biochemistry 25, 5468 5474), substitution at this site by alanine, serine, phenylalanine, isoleucine, or methionine did not abolish completely the pH shift nor affect operator affinity. Thus, ionization of the sulfhydryl residue does not account fully for the alterations in inducer affinity and cooperativity of binding observed with elevated pH. Substitution for Cys281 did, however, alter the kinetic parameters for inducer association with the protein. The polarity of the side chain at 281 influenced the rates of sugar binding, presumably by altering the rate of opening/closing of the binding site. Furthermore, the presence of the branched side chain of isoleucine at position 281 disrupted oligomerization of the repressor. In contrast to the tolerance for substitution at 281, the only amino acid side chain exchanges for Tyr282 which yielded tetrameric protein with near normal operator binding characteristics were phenylalanine and leucine; this result is consistent with studies of suppressed nonsense mutations at position 282 which indicated repression occurred only for the corresponding substitutions (Kleina, L. G., and Miller, J. H. (1990) J. Mol. Biol. 221, 295-318). Despite the tetrameric character of the Y282F mutant protein, the pH dependence and cooperativity of inducer binding for this mutant protein were altered. All amino acid substitutions other than phenylalanine and leucine at this position resulted in either monomeric protein or no detectable repressor in the cell. Thus, the hydrophobic character of the side chain at position 282 is essential for tetramer formation, and the phenyl ring alone alters inducer binding parameters. The monomeric mutant proteins with substitutions for Tyr282 exhibited lower stability than their tetrameric counterparts, and the absence of dimer formation suggests alterations at this site affect both dimer and tetramer interfaces. Based on previous genetic studies and our detailed mutant characterization, the region encompassing 281 and 282, indicated by secondary structure prediction to be a turn or coil, is essential for oligomer formation and additionally exerts a strong influence on the dynamic properties of the protein, presumably mediated by interactions at the subunit interface which regulate the rate of opening and closing of the inducer binding cleft. PMID- 1939244 TI - Holophytochrome assembly. Coupled assay for phytochromobilin synthase in organello. AB - Utilizing an in vitro coupled assay system, we show that isolated plastids from cucumber cotyledons convert the linear tetrapyrrole biliverdin IX alpha to the free phytochrome chromophore, phytochromobilin, which assembles with oat apophytochrome to yield photoactive holoprotein. The spectral properties of this synthetic phytochrome are indistinguishable from those of the natural photoreceptor. The plastid-dependent biliverdin conversion activity is strongly stimulated by both NADPH and ATP. Substitution of the nonnatural XIII alpha isomer of biliverdin for the IX alpha isomer affords a synthetic holophytochrome adduct with blue-shifted difference spectra. These results, together with experiments using boiled plastids, indicate that phytochromobilin synthesis from biliverdin is enzyme-mediated. Experiments where NADPH (and ATP) levels in intact developing chloroplasts are manipulated by feeding the metabolites 3 phosphoglycerate, dihydroxyacetone phosphate, and glucose 6-phosphate or by illumination with white light, support the hypothesis that the enzyme that accomplishes this conversion, phytochromobilin synthase, is plastid-localized. It is therefore likely that all of the enzymes of the phytochrome chromophore biosynthetic pathway reside in the plastid. PMID- 1939245 TI - Rap1A antagonizes the ability of Ras and Ras-Gap to inhibit muscarinic K+ channels. AB - Rap1A is a Ras-related GTP binding protein which has an amino acid sequence identical to that of Ras in the putative "effector" domain (amino acids 32-40). The binding of Rap1A to Ras-GTPase activating protein (GAP) through this domain is a potential mechanism for explaining the observation that Rap1A can antagonize the ability of oncogenic Ras to transform cells. It was recently shown (Yatani, A., Okabe, K., Polakis, P., Halenbeck, R., McCormick, F., and Brown, A. M. (1990) Cell 61, 769-776) that the activation of M2-muscarinic receptor-coupled K+ channels in heart is inhibited by the addition of exogenous Ras and Ras-GAP. We have made use of this system in the present paper to show that Rap1A is able to effectively block this inhibitory action of Ras-GAP. We observed that both Rap1A GDP and Rap1A-guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) were able to block the inhibitory effect of Ras-GAP upon channel activation. This effect occurred at picomolar concentrations of Rap1A, and the GTP gamma S-bound form of the protein was consistently found to be more potent than the GDP form. A Rap1A Thr35----Ala mutation which bound GTP gamma S did not prevent K+ channel inhibition by Ras-GAP, suggesting that the antagonism by wild type Rap1A involves an interaction with GAP in the effector domain. The effectiveness of Rap1A to inhibit Ras-GAP is dependent upon the amount of Ras-GAP present in the assay and can also be overcome by the addition of GTP-bound N-Ras (GC-43), suggesting a competitive mechanism is operative. Finally, a truncated form of Ras-GAP (GAP32) which is no longer dependent upon Ras for inhibition of the M2-activated K+ channel is also no longer sensitive to blockade by added Rap1A. These data support the concept of GAP as an effector of Ras action and indicate that Rap1A can serve as an inhibitor of Ras action in a system distinct from cell transformation by a competitive mechanism involving the GAP binding domain of Rap1A. PMID- 1939246 TI - Catalysis of acetyl-CoA cleavage and tetrahydrosarcinapterin methylation by a carbon monoxide dehydrogenase-corrinoid enzyme complex. AB - An enzyme complex containing carbon monoxide dehydrogenase and a corrinoid protein has been isolated from Methanosarcina barkeri. Sodium dodecyl sulfate-gel electrophoresis revealed five polypeptides of molecular masses alpha = 19,700, beta = 84,500, gamma = 63,200, delta = 53,000, and epsilon = 51,400 Da in equimolar amounts. One mol of cobamide cofactor was found per minimal alpha beta gamma delta epsilon unit. The molecular mass of the native complex was 1,600,000 Da by high pressure liquid chromatography (HPLC) gel filtration, which suggested an alpha 6 beta 6 gamma 6 delta 6 epsilon 6 oligomeric structure. Catalysis of a reaction involving cleavage of acetyl-CoA and methylation of tetrahydrosarcinapterin was indicated by spectrophotometric analyses; a time dependent absorption decrease in the 300-320 nm region was observed in the complete reaction mixture which contained acetyl-CoA, tetrahydrosarcinapterin, and the enzyme complex. In control samples lacking any one of the these components the absorption spectrum remained virtually unaltered. Reversed-phase HPLC analysis confirmed that tetrahydrosarcinapterin was converted to a product that co-eluted with authentic methyltetrahydrosarcinapterin. The product also exhibited the UV-visible absorption spectrum expected for methyltetrahydrosarcinapterin. Free CoA was identified as an additional product of the reaction. The carbonyl group of acetyl-CoA was oxidized to carbon dioxide. Spectral changes indicated concomitant Fe/S center reduction. Production of CoA was essentially stoichiometric with methyltetrahydrosarcinapterin formation and tetrahydrosarcinapterin consumption. Analyses during purification showed that catalytic activity was restricted exclusively to the fractions that contained the carbon monoxide dehydrogenase-corrinoid enzyme complex. PMID- 1939247 TI - Ultraviolet light activates blocking actions of dantrolene on intracellular Ca2+ release in bullfrog sympathetic neurones. AB - Effects of dantrolene, a blocker of intracellular Ca2+ release, on the oscillation of the intracellular Ca2+ ([Ca2+]i) induced by caffeine were studied in bullfrog sympathetic ganglion cells, using a Fura-2 fluorescence technique. Dantrolene blocked the Ca2+ oscillation only in the cell illuminated by ultraviolet light (335-385 nm). Likewise, the blocking effects on rhythmic Ca(2+) dependent hyperpolarizations, representing Ca2+ oscillations via activation of Ca(2+)-dependent K+ channel, occurred only under the illumination with ultraviolet light (335-385 nm), but not with visible light (404-417 nm). This wavelength dependence differs from the absorbance spectrum of dantrolene. On the other hand, dantrolene preirradiated with ultraviolet light under dark condition or ultraviolet light itself did not affect the [Ca2+]i oscillation. The blocking action was not prevented by the pretreatment of the cells with reducing agents. These results indicate that illumination of the Ca2+ release channel or dantrolene itself with ultraviolet light (possibly the former) is necessary for the drug to exert its blocking effect. Furthermore, dantrolene was found to decrease Fura-2 fluorescence and to increase cell autofluorescence, leading sometimes to a false decrease in the basal [Ca2+]i. PMID- 1939248 TI - Phenylarsine oxide causes an insulin-dependent, GLUT4-specific degradation in rat adipocytes. AB - An incubation of rat adipocytes with phenylarsine oxide (PAO) and then with insulin caused an inhibition of 3-O-methylglucose equilibrium exchange flux and a parallel reduction in cellular GLUT4 content detected by Western blots. Both the transport inhibition and the GLUT4 reduction were saturable with an increasing concentration of PAO showing essentially an identical Ki value of 35 microM. Both effects were not observed in the absence of insulin or if cells were incubated with insulin first. The reduction was specific to GLUT4; the immunoreactivities of GLUT1, insulin receptor, and clathrin were not affected in these experiments. The GLUT4 reduction occurred only in intact cells and was not observed in homogenized cells or fractionated membranes. GLUT4 in both the microsomal storage pool and the plasma membrane pool were affected with no indication of insulin induced recruitment impairment. GLUT4 reduction was not observed in the presence of chloroquine or at 18 degrees C suggesting involvement of the lysosomal pathway. Based on these results, we propose that there is a PAO-sensitive protein mechanism that controls an insulin-dependent GLUT4 degradation pathway in adipocytes. This protein mechanism and the GLUT4 degradation pathway may play an important role in determining the steady-state GLUT4 level in the insulin sensitive peripheral tissues in normal and diseased states. PMID- 1939249 TI - Cholate-independent retinyl ester hydrolysis. Stimulation by Apo-cellular retinol binding protein. AB - Apo-cellular retinol-binding protein (apoCRBP) activated the hydrolysis of endogenous retinyl esters in rat liver microsomes by a cholate independent retinyl ester hydrolase. A Michaelis-Menten relationship was observed between the apoCRBP concentration and the rate of retinol formation, with half-maximum stimulation at 2.6 +/- 0.6 microM (mean +/- S.D., n = 5). Two other retinol binding proteins, bovine serum albumin and beta-lactoglobulin, acceptors for the rapid and spontaneous hydration of retinol from membranes, had no effect up to 90 microM. These data suggest activation of the hydrolase by apoCRBP directly, rather than by facilitating removal of retinol from membranes. The hydrolase responding was the cholate-independent/cholate-inhibited retinyl ester hydrolase as shown by: 60% inhibition of the apoCRBP effect by 3 mM cholate; apoCRBP enhancement of retinyl ester hydrolysis in liver microsomes that had no detectable cholate-enhanced activity; inhibition of cholate-dependent, but not apoCRBP-stimulated retinyl ester hydrolysis by rabbit anti-rat cholesteryl esterase. Compared to the rate (mean +/- S.D. of [n] different preparations) supported by 5 microM apoCRBP in liver microsomes of 6.7 +/- 3.7 pmol/min/mg protein [10], microsomes from rat lung, kidney, and testes had endogenous retinyl ester hydrolysis rates of 1.8 +/- 0.3 [5], 0.5 +/- 0.2 [3], and 0.3 +/- 0.2 [5] pmol/min/mg protein, respectively. N-Ethylmaleimide and N-tosyl-L-phenylalanine chloromethyl ketone were potent inhibitors of apoCRBP-stimulated hydrolysis with IC50 values of 0.25 and 0.15 mM, respectively, but phenylmethylsulfonyl fluoride and diisopropyl-fluorophosphate were less effective with IC50 values of 1 mM, indicating the importance of imidazole and sulfhydryl groups to the activity. These data provide evidence of a physiological role for the cholate-independent hydrolase in retinoid metabolism and suggest that apoCRBP is a signal for retinyl ester mobilization. PMID- 1939250 TI - A1 adenosine receptors of bovine brain couple to guanine nucleotide-binding proteins Gi1, Gi2, and Go. AB - A1 adenosine receptors and associated guanine nucleotide-binding proteins (G proteins) were purified from bovine cerebral cortex by affinity chromatography (Munshi, R., and Linden, J. (1989) J. Biol. Chem. 264, 14853-14859). In this study we have identified the pertussis toxin-sensitive G protein subunits that co purify with A1 adenosine receptors by immunoblotting with specific antipeptide antisera. Gi alpha 1, Gi alpha 2, Go alpha, G beta 35, and G beta 36 were detected. Of the total [35S]guanosine 5'-O-(3-thio)triphosphate [( 35S]GTP gamma S) binding sites, Gi alpha 1 and Go alpha each accounted for greater than 37% whereas Gi alpha 2 comprised less than 13%. G beta 35 was found in excess over G beta 36. Low molecular mass (21-25 kDa) GTP-binding proteins were not detected. We also examined the characteristics of purified receptors and various purified bovine brain G proteins reconstituted into phospholipid vesicles. All three alpha subunits restored GTP gamma S-sensitive high affinity binding of the agonist 125I aminobenzyladenosine to a fraction (25%) of reconstituted receptors with a selectivity order of Gi2 greater than Go greater than or equal to Gi1 (ED50 values of G proteins measured as fold excess over the receptor concentration were 4.7 +/- 1.2, 24 +/- 5, and 34 +/- 7, respectively). Furthermore, receptors occupied with the agonist R-phenylisopropyladenosine catalytically increased the rate of binding of [35S]GTP gamma S to reconstituted G proteins by 6.5-8.5-fold. These results suggest that A1 adenosine receptors couple indiscriminately to pertussis toxin-sensitive G proteins. PMID- 1939251 TI - Characterization of a cis-acting element required for efficient transcriptional activation of the collagen IV enhancer. AB - Two regulatory regions in the murine collagen IV enhancer were identified. Transient transfection assays delimited a 210-base pair fragment within the first intron of the alpha 1(IV) collagen gene that had significant transcriptional enhancer activity. DNase I protection and gel mobility shift confirmed that two regions, designated footprints A and B, within this fragment bound nuclear factors. Gel shift studies suggested that the CCTTATCTCTGATGG motif (A-34) in the footprint A region was important for specific nuclear factor binding. Mutations in the A-34 motif abolished factor binding as detected by gel shift and resulted in a significant decrease in enhancer activity in transient transfection assays of F9 teratocarcinoma cells. Two putative transcription factors of Mr = 37,000 and Mr = 94,000, which interact with the A-34 motif, were purified from Engelbreth-Holm-Swarm tumor tissue using DEAE-Sephacel, heparin-Sepharose, salmon sperm DNA-Sepharose, and specific A-34 oligonucleotide affinity chromatography. Southwestern analysis revealed that both of these factors were capable of binding the A-34 oligonucleotide directly and did not require additional subunits for binding. These data suggest that positively acting transcription factor(s) interact with the A-34 site in the enhancer and are required for efficient transcription of the alpha 1 and alpha 2(IV) collagen chain genes. PMID- 1939252 TI - Nuclear import substrates compete for a limited number of binding sites. Evidence for different classes of yeast nuclear import receptors. AB - A nuclear receptor likely involved in nuclear protein import is described. Purified ATP-depleted yeast nuclei show saturable high-affinity binding of the yeast nuclear protein Mcm1. The dissociation constant for the binding is 0.5 microM, and the number of binding sites is approximately 3,500 per nucleus, equivalent to 10-30 binding sites per nuclear pore. Mcm1 competes with other yeast nuclear proteins Ste12 and Swi5, but not with Rap1 or Nop1, indicating that there may be different types of import receptors. Bound Mcm1 is resistant to extraction by nucleases, salt, and non-ionic detergent, but can be released by 5 M urea, suggesting that Mcm1 binds to a yeast equivalent of the nuclear pore complex-lamina fraction of higher eukaryotes. PMID- 1939253 TI - Protease specificity and heparin binding and activation of recombinant protease nexin I. AB - Structural and functional properties of alpha-protease nexin I (alpha-PNI) expressed in Chinese hamster ovary cells were studied. All three cysteines were in the reduced form, showing that the potential disulfide bridge between residues Cys117 and Cys131 was not formed. Heparin association rate enhancements were from ka = 8.3 x 10(5) to 0.7-1.6 x 10(9) M-1 s-1 for the interaction of PNI with thrombin, from ka = 5.1 x 10(3) to 3.5 x 10(5) M-1 s-1 for interaction with Factor Xa, and from ka = 2.2 x 10(6) to 1.0 x 10(7) M-1 s-1 for interaction with trypsin; there was no rate enhancement of the plasmin interaction (ka = 1.0 x 10(5) M-1 s-1). The minimal heparin pentasaccharide had no effect on these interactions. Cleavage of the reactive center loop of PNI by three different proteases gave the typical stressed to relaxed change in thermal stability, but unlike with antithrombin III, there was no loss of heparin affinity. A similar difference from antithrombin was that PNI-thrombin complexes retained normal heparin affinity. These results are compatible with a role for protease nexin I as a cell-associated thrombin inhibitor that remains bound to the cell surface even after complexing with the protease, as compared with the role of antithrombin III as a circulating inhibitor of thrombin that becomes activated on binding to the microvasculature and is released on complex formation. PMID- 1939254 TI - Stimulation of glycogen synthesis by proglycosyn (LY177507) by isolated hepatocytes of normal and streptozotocin diabetic rats. AB - The phenacylimidazolium compound LY177507 was shown by Harris et al. (Harris, R. A., Yamanuchi, K., Roach, P. J., Yen, T. T., Dominiani, S. J., and Stephens, T. W. (1989) J. Biol. Chem. 264, 14674-14680) to stimulate glycogen synthesis greatly in isolated rat hepatocytes. We extended studies with this compound, designated proglycosyn (Yamaguchi, K., Stephens, T. W., Chikadar, K., Depaoli Roach, A., And Harris, R. A. (1991) Diabetes 40, (Suppl. 1) 102 (abstr.] employing hepatocytes from normal and streptozotocin diabetic rats. Proglycosyn is more effective than amino acids in stimulating glycogen synthesis. In cells incubated with glucose, lactate, or dihydroxyacetone the effect of glutamine and proglycosyn was synergistic. In cells incubated with glucose plus lactate, or glucose plus dihydroxyacetone, the stimulation by the two agonists was additive. Proglycosyn diverted the gluconeogenic flux from glucose to glycogen. The maximal rates of glycogen deposition attained in the presence of glutamine and proglycosyn from cells incubated with glucose plus lactate, or glucose plus dihydroxyacetone, where about 80 and 110 mumols/h/g of liver, respectively. Proglycosyn depressed glycogenolysis in hepatocytes of fed rats and stimulated glycogen synthesis from lactate and dihydroxyacetone. The incorporation of [U 14C]glucose and [U-14C]lactate in these cells occurred in the presence of glycogen breakdown or exceeded net production, indicating the occurrence of recycling of glycogen in hepatocytes of fed rats. Hepatocytes from fasted streptozotocin diabetic rats contained high levels of glycogen. Glycogenolysis was markedly depressed by proglycosyn. Glycogen synthesis from lactate and dihydroxyacetone in these cells was stimulated by glutamine and proglycosyn in a fashion similar to that in cells from fasted control rats, and the rates of glycogen synthesis were similar in cells of control and diabetic rats. With glucose as sole substrate, glutamine did not stimulate glycogen synthesis. When both agonists were present, there was a marked synergism and substantial glycogen formation. Streptozotocin diabetic rats prior to the onset of cachexia have a normal capacity for glycogen synthesis. PMID- 1939255 TI - Biosynthesis of phycobilins. Ferredoxin-mediated reduction of biliverdin catalyzed by extracts of Cyanidium caldarium. AB - Cell-free extract of the unicellular rhodophyte, Cyanidium caldarium catalyzes enzymatic reduction of biliverdin IX alpha to phycocyanobilin, the chromophore of the light-harvesting phycobiliprotein, phycocyanin. The enzyme activity is soluble, and the required reductant is NADPH. The extract has been separated into three protein fractions, all of which are required to reconstitute biliverdin reduction. One fraction contains ferredoxin, which was identified by its absorption spectrum. This fraction could be replaced with commercial ferredoxin derived from spinach or the red alga, Porphyra umbilicalis. The second protein fraction contains ferredoxin-NADP+ reductase, which was identified by the ability to catalyze ferredoxin-dependent reduction of cytochrome c in the presence of NADPH. This fraction could be replaced with commercial spinach ferredoxin-NADP+ reductase. These two components appear to be identical to previously described components of the algal heme oxygenase system that catalyzes biliverdin IX alpha formation from protoheme in C. caldarium extracts. The third protein fraction, in the presence of the first two (or their commercial counterparts) plus NADPH, catalyzes the reduction of biliverdin IX alpha to phycocyanobilin. The results indicate that the transformation of biliverdin to phycocyanobilin catalyzed by C. caldarium extracts is a ferredoxin-linked reduction process. The results also suggest the possibility that heme oxygenation and biliverdin reduction may occur in C. caldarium on associated enzyme systems. PMID- 1939256 TI - Biosynthesis of phycobilins. 3(Z)-phycoerythrobilin and 3(Z)-phycocyanobilin are intermediates in the formation of 3(E)-phycocyanobilin from biliverdin IX alpha. AB - An enzyme extract from the phycocyanin-containing unicellular rhodophyte, Cyanidium caldarium, reductively transforms biliverdin IX alpha to phycocyanobilin, the chromophore of phycocyanin, in the presence of NADPH. Unpurified cell extract forms both 3(E)-phycocyanobilin, which is identical to the major pigment that is released from phycocyanin by methanolysis, and 3(Z) phycocyanobilin, which is obtained as a minor methanolysis product. After removal of low molecular weight material from the cell extract, only 3(Z)-phycocyanobilin is formed. 3(E)-Phycocyanobilin formation from biliverdin IX alpha, and the ability to isomerize 3(Z)-phycocyanobilin to 3(E)-phycocyanobilin, are reconstituted by the addition of glutathione to the incubation mixture. Partially purified protein fractions derived from the initial enzyme extract form 3(Z) phycocyanobilin plus two additional, violet colored bilins, upon incubation with NADPH and biliverdin IX alpha. Further purified protein fractions produce only the violet colored bilins from biliverdin IX alpha. One of these bilins was identified as 3(Z)-phycoerythrobilin by comparative spectrophotometry, reverse phase high pressure liquid chromatography, and 1H NMR spectroscopy. A C. caldarium protein fraction catalyzes the conversion of 3(Z)-phycoerythrobilin to 3(Z)-phycocyanobilin. This fraction also catalyzes the conversion of 3(E) phycoerythrobilin to 3(E)-phycocyanobilin. The conversion of phycoerythrobilins to phycocyanobilins requires neither biliverdin nor NADPH. The synthesis of phycoerythrobilin and its conversion to phycocyanobilin by extracts of C. caldarium, a species that does not contain phycoerythrin, indicates that phycoerythrobilin is a biosynthetic precursor to phycocyanobilin. The enzymatic conversion of the ethylidine group from the Z to the E configuration suggests that the E-isomer is the precursor to the protein-bound chromophore. PMID- 1939257 TI - Biosynthesis of phycobilins. 15,16-Dihydrobiliverdin IX alpha is a partially reduced intermediate in the formation of phycobilins from biliverdin IX alpha. AB - A partially purified protein fraction from the phycocyanin-containing unicellular rhodophyte, Cyanidium caldarium, reductively transforms biliverdin IX alpha to a violet colored bilin in the presence of NADPH, ferredoxin, and ferredoxin-NADP+ reductase. This bilin has a violin-like absorption spectrum with maxima at 335 and 560 nm in methanolic HCl and at 337, 567, and 603-604 nm in CHCl3. The bilin has been determined to be 15,16-dihydrobiliverdin IX alpha by comparative spectrophotometry and 1H NMR spectroscopy. This product of biliverdin IX alpha reduction is converted enzymatically to phycobilins by further reduction. A general biosynthetic pathway is proposed which accounts for the formation of the phycobilins from biliverdin IX alpha by a two-step reduction process followed by isomerization. PMID- 1939258 TI - pH-dependent pore formation properties of pardaxin analogues. AB - The interaction of pardaxin, a shark-repellent neurotoxin, and its charge modified analogues with vesicles and human erythrocytes is described. The following six analogues and derivatives were synthesized by a solid phase method: [Glu8, Glu16]pardaxin, [N1-succinamido,Glu8,Glu16]pardaxin, [N1,Lys8,Lys16 triacetyl]pardaxin, des-[1----9]pardaxin (Shai, Y., Bach, D., and Yanovsky, A. (1990) J. Biol. Chem. 265, 20202-20209), and des-[1----9] [Glu16]pardaxin. The relative hydrophobic characteristics of the analogues were examined using reverse phase high performance liquid chromatography. The pH-dependent spectroscopic and functional characteristics of the analogues were also investigated at either neutral or acidic pH. Spectroscopic characterization was achieved by measuring circular dichroism both before and after binding to vesicles, at either neutral or acidic pH. The ability of the peptides to dissipate a diffusion potential, to cause calcein release or the pH-dependent release of 8-aminonaphthalene-1,3,6 trisulfonic acid disodium salt/p-xylene-bis[pyridinium bromide] from sonicated unilamellar liposomes, as well as measurements of cytolytic activity on human erythrocytes, served to functionally characterize the peptides. We show a direct correlation between alpha-helical content, the analogues' hydrophobicity, and their pore-forming properties at the different pH values tested. We also demonstrate that the charge of the N terminus and of the peptide backbone, but not of the C terminus, affects the secondary structure as well as the activities of the analogues. Finally, we show that the cytolytic activity of pardaxin at neutral pH is not retained by any of the analogues. PMID- 1939259 TI - Leucine aminopeptidase-like activity in Aplysia hemolymph rapidly degrades biologically active alpha-bag cell peptide fragments. AB - We have investigated the role that proteolytic enzymes in Aplysia hemolymph play in the inactivation of the neurotransmitter alpha-bag cell peptide (alpha-BCP(1 9), Ala-Pro-Arg-Leu-Arg-Phe-Tyr-Ser-Leu). alpha-BCP fragments containing Pro in positions 1 or 2, or Tyr in position 1, were degraded relatively slowly (half life, t1/2 = 10-64 min), whereas fragments lacking these residues were degraded relatively rapidly (t1/2 = 0.5-2.7 min). Of 12 peptidase inhibitors tested, only bestatin, amastatin, and phenanthroline significantly inhibited alpha-BCP(3-9) degradation. alpha-BCP(3-9) yielded only four observable cleavage products (in order of decreasing abundance at early time points): alpha-BCP(4-9), alpha-BCP(5 9), alpha-BCP(6-9), and alpha-BCP(7-9). Degradation of alpha-BCP(3-9), alpha BCP(4-9), alpha-BCP(5-9), alpha-BCP(6-9), or alpha-BCP(7-9) was strongly inhibited by bestatin, moderately inhibited by amastatin, and not inhibited by arphramenine B. The rates of degradation of eight alpha-BCP fragments and three other peptides in plasma were well correlated with their rates of degradation in mammalian leucine aminopeptidase (LAP, EC 3.4.11.1). Collectively our data support the following ideas. 1) In hemolymph one or more LAP-like enzymes rapidly and sequentially cleave alpha-BCP(3-9) or other small peptides lacking Pro at positions 1 or 2 or Tyr at position 1. 2) LAP-like peptidases in hemolymph may act in concert with previously described ganglionic peptidases to degrade neurally released alpha-BCP(1-9) and alpha-BCP(1-8) into inactive fragments. PMID- 1939260 TI - Site-directed mutagenesis of a conserved region of the 5-enolpyruvylshikimate-3 phosphate synthase active site. AB - The active site of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) has been probed using site-directed mutagenesis and inhibitor binding techniques. Replacement of a specific glycyl with an alanyl or a prolyl with a seryl residue in a highly conserved region confers glyphosate tolerance to several bacterial and plant EPSPS enzymes, suggesting a high degree of structural conservation between these enzymes. The glycine to alanine substitution corresponding to Escherichia coli EPSPS G96A increases the Ki(app) (glyphosate) of petunia EPSPS 5000-fold while increasing the Km(app)(phosphoenolpyruvate) about 40-fold. Substitution of this glycine with serine, however, abolishes EPSPS activity but results in the elicitation of a novel EPSP hydrolase activity whereby EPSP is converted to shikimate 3-phosphate and pyruvate. This highly conserved region is critical for the interaction of the phosphate moiety of phosphoenolpyruvate with EPSPS. PMID- 1939261 TI - A 9-base pair deletion in COL1A1 in a lethal variant of osteogenesis imperfecta. AB - A proband with lethal osteogenesis imperfecta has been investigated for the causative defect at the levels of collagen protein, mRNA, and DNA. Analysis of type I collagen synthesized by the proband's fibroblasts showed excessive post translational modification of alpha 1(I) chains along the entire length of the helix. Oververmodification of alpha chains could be prevented by incubation of the cells at 30 rather than 37 degrees C, and the thermal stability of the triple helix, as determined by protease digestion, was normal. RNase A cleavage of RNA:RNA hybrids formed between the proband's mRNA and antisense RNA derived from normal pro-alpha 1(I) chain cDNA clones was used to locate an abnormality to exon 43 of the proband's pro-alpha 1(I) collagen gene (COL1A1). The nucleotide sequence of the corresponding gene region showed, in one allele, the deletion of 9 base pairs, not present in either parent, within a repeating sequence of exon 43. The mutation causes the loss of one of three consecutive Gly-Ala-Pro triplets at positions 868-876, but does not otherwise disrupt the Gly-X-Y sequence. Procollagen processing in fibroblast cultures and susceptibility of the mutant collagen I to cleavage with vertebrate collagenase were normal, indicating that the slippage of collagen chains by one Gly-X-Y triplet does not abolish amino propeptidase and collagenase cleavage sites. How the mutation produces the lethal osteogenesis imperfecta phenotype is not entirely clear; the data suggest that the interaction of alpha chains immediately prior to helix formation may be affected. PMID- 1939262 TI - In vivo and in vitro inhibition of JE gene expression by glucocorticoids. AB - Glucocorticoids are potent anti-inflammatory agents which affect cell growth and migration in a wide variety of systems and have profound effects on monocytes, decreasing their circulating number as well as inhibiting their accumulation at sites of inflammation and injury. Although the mechanisms by which glucocorticoids regulate gene induction have been established, the mechanisms by which they inhibit inflammation or cell growth and migration have yet to been determined. JE is one of the most abundant genes induced by platelet-derived growth factor (PDGF) in vitro and is also induced in vivo in response to ischemia or injury. JE encodes a low molecular weight glycoprotein that functions in part as a monocyte chemotactic factor and thus may be important in recruiting monocytes to sites of tissue injury and/or inflammation. We report that glucocorticoids block the induction of JE mRNA by serum or PDGF in cultured vascular smooth muscle cells. The effect of glucocorticoids appears largely due to destabilization of JE mRNA and has specificity for JE, in that other "early" PDGF-inducible genes are not inhibited by glucocorticoids. The effect of glucocorticoids also occurs in vivo: methyl prednisolone blocks the constitutive expression and inhibits the ischemia-induced elevation of JE mRNA levels in rat kidneys. The inhibition of JE mRNA accumulation by glucocorticoids may be related to the anti-inflammatory effects of these agents and defines JE as a member of what may be a group of PDGF-inducible genes that are responsive to corticosteroids. PMID- 1939263 TI - Pyruvate dehydrogenase and pyruvate carboxylase. Sites of pretranslational regulation by glucose of glucose-induced insulin release in pancreatic islets. AB - It has been shown previously that glucose-induced insulin release is completely absent in rat pancreatic islets that had been cultured for 1 day at low glucose (1 mM) and that it is restored by culturing islets for a 2nd day at high (20 mM) glucose (MacDonald, M. J., Fahien, L. A., McKenzie, D. I., and Moran, S. M. (1991) Am. J. Physiol. 259, E548-E554). It has been suggested that the incapacitation of glucose's insulinotropism is due to down-regulation of the synthesis of enzymes that process glucose's metabolic signal for insulin release. In the current study, results of metabolic, enzymic, and molecular biologic experiments were each consistent with (an) intramitochondrial site(s) of down regulation in islets cultured at low glucose. Glucose metabolism was inhibited 80% in islets cultured at 1 mM glucose. The suppression of release of 14CO2 from [6-14C]glucose greater than from [U-14C]glucose greater than [3,4-14C]glucose greater than from [1-14C]glucose in islets cultured at low glucose indicated a mitochondrial site of down-regulation because C-6 of glucose can only be converted to CO2 in the citric acid cycle, whereas C-1 can be released as CO2 in the 6-phosphogluconate dehydrogenase [corrected] reaction, and C-6 of glucose dwells in the citric acid cycle longer than carbons 2-5 of glucose. Since carbons 3 and 4 of glucose can be decarboxylated in the pyruvate dehydrogenase reaction, incomplete suppression of CO2 formation from these carbons is consistent with suppression of pyruvate carboxylation as well as decarboxylation. Formation of 3HOH from [5-3H]glucose was equal in the two groups of islets, indicating that glycolysis as far as phosphoenolpyruvate was intact. This idea was supported by assays which showed that activities of enzymes of the glycolytic pathway between glucokinase/hexokinase and pyruvate kinase were equal in both types of islets. Additional studies indicated that regulation by glucose was at transcription of genes coding for some mitochondrial enzymes. Glucokinase, malic enzyme, and fumarase mRNAs were not affected by glucose, whereas the pyruvate dehydrogenase E1 alpha subunit and pyruvate carboxylase mRNAs were decreased 85-90% in islets cultured at 1 mM glucose. Pyruvate dehydrogenase enzyme activity was decreased to a similar extent in these islets. About 24 h was required for maximal (de)induction of pyruvate dehydrogenase E1 alpha and pyruvate carboxylase mRNAs, and the amounts of transcripts were proportional to the concentrations of glucose between 1 and 20 mM.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1939264 TI - Compartmentation of multiple forms of creatine kinase in the distal nephron of the rat kidney. AB - Creatine kinase enzymes are present in tissues such as muscle and brain to interconvert creatine phosphate and ADP, thus providing a system to interconnect energy production and utilization (Bessman, S. P., and Carpenter, C. L. (1985) Annu. Rev. Biochem. 54, 831-862). Creatine kinase isoenzymes in kidney have received little attention since kidney contains relatively low creatine kinase activity compared with muscle and brain and because there is disagreement regarding the identity of the specific isoforms expressed in kidney. Using a combination of chromatographic and immunological techniques, we have identified two isoforms of creatine kinase in rat kidney supernatants, B creatine kinase, and the non-sarcomeric form of the mitochondrial creatine kinase, which represent 82 and 15%, respectively, of the total creatine kinase activity in this tissue. The identity of the non-muscle form of the mitochondrial creatine kinase was confirmed by N-terminal sequence analysis and compared with recently published cDNA sequences (Haas, R. C., and Strauss, A. W. (1990) J. Biol. Chem. 265, 6921 6927). We prepared multiple antisera specific for each isoform using synthetic peptide immunogens based upon nonhomologous regions from the primary sequence of each creatine kinase isoform. Immunocytochemical results demonstrate that both creatine kinase isoforms are colocalized in the inner stripe of the outer medulla in tubules of the distal nephron. A similar distribution of creatine kinase isoforms was obtained when different layers of the renal cortex and medulla were examined for creatine kinase activity and isozyme content using nondenaturing electrophoresis. In general, the distribution of creatine kinase enzymes in kidney corresponds to the regions of greatest ATP utilization, oxygen consumption, and sodium transport. These results suggest a role for creatine kinase enzymes in the coupling of ion transport and oxidative phosphorylation in the distal nephron of the mammalian kidney. PMID- 1939265 TI - Myosin heavy chain gene expression in mouse embryoid bodies. An in vitro developmental study. AB - Embryoid bodies (EBs) are obtained when mouse pluripotential embryonic stem cells are grown in the absence of an embryonic fibroblast feeder layer. Seven- to 9-day old EBs undergo rhythmical, spontaneous contractions and express the appropriate tissue- and developmental stage-specific cardiac and skeletal myosin heavy chain (MHC) genes. To study the expression patterns of these MHC genes in vitro we isolated and partially sequenced the cDNAs expressed in EBs such that specific oligonucleotides suitable for polymerase chain reaction analyses and appropriate riboprobes for in situ hybridizations could be made. The data show the beta cardiac gene is expressed first during EB development (days 3 and 4), and alpha cardiac gene expression begins at approximately day 8. A similar pattern of expression is also detected during mouse embryogenesis in utero. Only those EBs that expressed both the alpha- and beta-cardiac transcripts contracted. In situ hybridization of EBs using riboprobes shows that the spatial distribution of the cardiac MHC transcripts differs. No expression of the genes was detected in day 8 or older nonbeating EBs. These data suggest that developing EBs closely mimic the pre- and early postsomitic patterns of in vivo expression of the cardiac MHC genes and thus provide a useful system in which to study early aspects of mammalian cardiogenesis. PMID- 1939266 TI - Purification, characterization, and amino acid sequences of pepsinogens and pepsins from the esophageal mucosa of bullfrog (Rana catesbeiana) AB - Two pepsinogens (pepsinogens 1 and 2) were purified from the esophageal mucosa of the bullfrog (Rana catesbeiana), and their molecular weights were determined to be 40,100 and 39,200, respectively, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The NH2-terminal 70-residue sequences of both pepsinogens are the same, including the 36-residue activation segment. Furthermore, a cDNA clone encoding frog pepsinogen was obtained and sequenced, which permitted deduction of the complete amino acid sequence (368 residues) of one of the pepsinogen isozymogens. The calculated molecular weight of the protein (40,034) coincided well with the values obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results are incompatible with the previous report (Shugerman R. P., Hirschowitz, B. I., Bhown, A. S., Schrohenloher, R. E., and Spenney, J. G. (1982) J. Biol. Chem. 257, 795-798) that the major pepsinogen isolated from the bullfrog esophageal gland is a unique "mini" pepsinogen with a molecular weight of approximately 32,000-34,000. The two pepsinogens were immunologically indistinguishable from each other and related to human pepsinogen C. The deduced amino acid sequence was also more homologous with those of pepsinogens C than those of pepsinogens A and prochymosin. These results indicate that the frog pepsinogens belong to the pepsinogen C group. They were both glycoproteins, and therefore, this is the first finding of carbohydrate containing pepsinogens C. Both pepsinogens were activated to pepsins in the same manner by an apparent one-step mechanism. The resulting pepsins were enzymatically indistinguishable from each other, and their properties resembled those of tuna pepsins. PMID- 1939267 TI - Nucleotide excision repair of DNA by human cell extracts is suppressed in reconstituted nucleosomes. AB - Nucleotide excision repair is a complex biochemical process that corrects DNA damage caused by a broad spectrum of physical and chemical agents. We examined the effect of the assembly of ultraviolet-irradiated plasmid DNA into nucleosomes on nucleotide excision repair supported by human cell extracts. Repair synthesis in unassembled UV-irradiated plasmid DNA was readily detected in extracts from repair-proficient human cells. In contrast, repair synthesis was markedly suppressed in UV-irradiated DNA assembled into nucleosomes (minichromosomes). This suppression occurred at a step(s) which precedes repair synthesis during nucleotide excision repair. Human cell extracts were unable to effectively assemble plasmid DNA into nucleosomes under repair synthesis conditions. The addition of purified histones to the extracts restored their capacity for nucleosome assembly and simultaneously led to the suppression of repair synthesis. We propose that the preferential repair of actively transcribed genes relative to transcriptionally silent genes may reflect altered nucleosome conformation during transcription. PMID- 1939268 TI - Phosphorylation of maize RAB-17 protein by casein kinase 2. AB - The maize gene RAB-17, which is responsive to abscisic acid, encodes a basic glycine-rich protein containing, in the middle part of its sequence, a cluster of 8 serine residues followed by a putative casein kinase 2-type substrate consensus sequence. This protein was found to be highly phosphorylated in vivo. Here, we show that RAB-17 protein is a real substrate for casein kinase 2. RAB-17 protein is phosphorylated in vitro by casein kinase 2 isolated from rat liver cytosol and from maize embryos. A maximum of 4 mol of phosphate were incorporated per mol of RAB-17 protein following incubation with casein kinase 2. Phosphopeptide mapping experiments show that the peptide phosphorylated by casein kinase 2 in vitro is identical to that derived from the protein phosphorylated in vivo. Purification by high performance liquid chromatography and partial sequencing of the phosphopeptide indicate that it corresponds to the region of the protein (residues 56-89) containing the cluster of serine residues. Our results indicate that RAB-17 is phosphorylated by casein kinase 2 or a kinase with a similar specificity and that phosphorylation takes place in the serine cluster region of the protein both in vitro and in vivo. PMID- 1939269 TI - Characterization of rabbit lung lysosomes and their role in surfactant dipalmitoylphosphatidylcholine catabolism. AB - Although alveolar surfactant is rapidly catabolized in adult rabbit lungs, the pathways have not been characterized. Pathways of surfactant secretion and recycling involve lamellar bodies and multivesicular bodies, organelles shown to be related to lysosomes by cytochemistry and autoradiography. Since lysosomes are central to intracellular catabolic events, it is possible that lysosomes are involved in intrapulmonary surfactant catabolism. Lysosomes relatively free of contaminating organelles (as determined morphologically and by marker enzymes for mitochondria, endoplasmic reticulum, peroxisomes, and plasma membranes) were obtained from post-lavage lung homogenates of 1-kg rabbits by differential centrifugation in buffered sucrose and gradient separation in percoll (density, 1.075-1.165). The role of lung lysosomes in catabolism of dipalmitoylphosphatidylcholine (DPC) was then studied in rabbits killed 4, 12, and 24 h following intratracheal injection of [3H]DPC and [14C] dihexadecyl phosphatidylcholine (DPC-ether). While equal amounts of label were in the lamellar body containing fractions at 4 h, nearly 6-fold more DPC-ether label than DPC label was recovered in the lysosomal fractions. By 24 h, there was 15 fold more DPC-ether in the lysosomes. This is the first report of successful isolation of lysosomes relatively free of other organelles from rabbit lungs. The tracer studies indicate DPC and DPC-ether follow similar intracellular processing after alveolar uptake. The subsequent accumulation of the ether analog in the lysosomal fractions supports a role for these organelles in surfactant DPC catabolism. PMID- 1939271 TI - Abortive initiation is increased only for the weakest members of a set of down mutants of the adenovirus 2 major late promoter. AB - We have shown that accurate initiation of productive RNA synthesis in vitro at the adenovirus 2 major late promoter is accompanied by abortive initiation of very short transcripts (Luse, D. S., and Jacob, G. A. (1987) J. Biol. Chem. 262, 14990-14997). We made a set of sequence variants of this promoter, using every possible base at position -28 (in the TATA box) in the context of either the normal base (A) or a T at position +1 on the nontemplate strand. All changes from wild type reduced promoter strength. The two weakest promoters were 10- and 30 fold less active than wild type in productive RNA synthesis. We tested the possibility that the down mutations also caused an increase in the proportion of in vitro initiations which are abortive. This effect was seen only with the two weakest members of the promoter set. For these promoters, which share an A----C change at the -28 position of the TATA box, the ratio of abortive to productive initiations was 3-4-fold higher than for the other promoters. Interestingly, the sequence change at +1, although a down mutation, did not lead to an increase in abortive initiation. PMID- 1939270 TI - Altered regulation of mRNA levels encoding the type I isozyme of cAMP-dependent protein kinase in neoplastic mouse lung epithelial cells. AB - Neoplastic mouse lung epithelial cells express greatly diminished activity, protein, and mRNA for the type I isozyme of cAMP-dependent protein kinase (PKA I). To address the mechanism of this decrease, the turnover rate of PKA subunit mRNA was examined. Northern blot analysis of PKA mRNAs from transcriptionally inhibited cells indicated that these messages exhibit different stabilities and that they are more stable in neoplastic E9 cells than in normal C10 cells. This suggests that the mechanism of decreased PKA I mRNA in E9 cells resides at the level of transcription. To examine whether this was due to an altered responsiveness to agents which regulate PKA transcription, PKA levels were experimentally manipulated in C10 and E9 cells by long-term treatment with forskolin or 8-chloro-cAMP. PKA activity and the concentration of RI (regulatory subunit of PKA I) and C (catalytic subunit) are coordinately regulated in both cell lines, but this does not reflect the changes in PKA I subunit mRNAs. RI alpha mRNA is specifically induced by forskolin in normal C10 cells, but not in E9 cells. C alpha mRNA is forskolin-inducible in E9 cells, but this enhanced level of expression does not approach that found constitutively in C10 cells. Thus, while C10 and E9 undergo similar changes in PKA I protein subunits following these treatments, a differential modulation of their PKA I mRNA occurs. These cell-specific mRNA responses to cAMP-mediated induction suggest that the mechanism of the decreased constitutive concentration of PKA I in E9 cells involves altered regulation of PKA I mRNAs. PMID- 1939272 TI - Effects of amino acid sequence, buffers, and ionic strength on the rate and mechanism of deamidation of asparagine residues in small peptides. AB - The nonenzymatic rates of deamidation of Asn residues in a series of pentapeptides with the sequences VSNXV and VXNSV, where X is one of 10 different amino acids, were determined at neutral, alkaline, and acid pH values. The results demonstrate that in neutral and alkaline solutions the amino acid residue on the amino side of the Asn had little or no effect on the rate of deamidation regardless of its charge or size. The group on the carboxyl side of Asn affected the rate of deamidation significantly. Increasing size and branching in the side chain of this residue decreased the rate of deamidation by as much as 70-fold compared to glycine in the N-G sequence, which had the greatest rate of deamidation. In acidic solution, the rate of deamidation of the Asn residue was not affected by the amino acid sequence of the peptide. The products for each deamidation reaction were tested for the formation of isoAsp residues. In neutral and alkaline solutions, all products showed that the isoAsp:Asp peptide products were formed in about a 3:1 ratio. In acidic solution, the Asp peptide was the only deamidation product formed. All peptides in which a Ser residue follows the Asn residue were found to undergo a peptide cleavage reaction in neutral and alkaline solutions, yielding a tripeptide and a dipeptide. The rate of the cleavage reaction was about 10% of the rate of the deamidation pathway at neutral and alkaline pH values. The rates of deamidation of Asn residues in the peptides studied were not affected by ionic strength, and were not specific base catalyzed. General base catalysis was observed for small bases like ammonia. A model for the deamidation reaction is proposed to account for the observed effects. PMID- 1939273 TI - Molecular cloning and expression of a mouse muscle cDNA encoding adenylosuccinate synthetase. AB - Adenylosuccinate synthetase (EC 6.3.4.4) catalyzes the first step in formation of AMP from IMP. At least two isozymes exist in vertebrate tissue. An acidic form, present in most tissues, has been suggested to be involved in de novo biosynthesis while a basic isozyme, which predominates in muscle, appears to function in the purine nucleotide cycle. Antibodies specific for the basic isozyme detect a single protein in mouse tissues with highest levels in skeletal muscle, tongue, esophagus, and heart tissue consistent with a role for the enzyme in muscle metabolism. A series of degenerate oligonucleotides were constructed based on peptide sequences from purified rat muscle enzyme and then used to clone a mouse muscle cDNA encoding the basic isozyme. The clone contains a open reading frame of 1356 bases with 452 amino acids. Northern analysis of RNA from mouse tissues showed a tissue distribution similar to that of the protein, indicating a high level of gene expression in muscle. Transfection of COS cells with the mouse muscle cDNA allows expression of a functional protein with a molecular mass of approximately 50 kDa, consistent with the open reading frame and the size of the isolated rat enzyme. The deduced amino acid sequence of the mouse synthetase is 47 and 37% identical to the synthetase sequences from Dictyostelium discoideum and Escherichia coli, respectively. The availability of antibodies and cDNA clones specific for the basic isozyme of adenylosuccinate synthetase from muscle will facilitate future genetic and biochemical analysis of this protein and its role in muscle physiology. PMID- 1939275 TI - Photoaffinity labeling and fatty acid permeation in 3T3-L1 adipocytes. AB - Long chain fatty acid uptake was investigated in 3T3-L1 cells. Differentiation of these cells from fibroblasts to adipocytes was accompanied by an 8.5-fold increase in the rate of oleate uptake. This was saturable in adipocytes with apparent Kt and Vmax values of 78 nM and 16 nmol/min/mg cell protein, respectively. A number of proteins in various subcellular fractions of differentiated cells were labeled with the photoreactive fatty acid 11-m diazirinophenoxy[11-3H]undecanoate. A 15-kDa cytoplasmic protein was induced upon differentiation to adipocytes. This protein was labeled with the photoreactive fatty acid in cytoplasm isolated from differentiated adipocytes, but not in cytoplasm from undifferentiated, fibroblastic cells. Furthermore, a high affinity fatty acid binding protein of 22 kDa was identified in plasma membranes of undifferentiated cells, and its level of labeling increased 2-fold upon differentiation. These results indicate the usefulness of the photoreactive fatty acid in identifying cellular fatty acid binding proteins, and its potential to elucidate the spatial and temporal distribution of fatty acids in intact cells. PMID- 1939274 TI - Agonist binding site of Torpedo electric tissue nicotinic acetylcholine receptor. A negatively charged region of the delta subunit within 0.9 nm of the alpha subunit binding site disulfide. AB - The positively charged quaternary ammonium group of agonists of the nicotinic acetylcholine (ACh) receptor binds to a negative subsite at most about 1 nm from a readily reducible disulfide. This disulfide is formed by alpha Cys192 and Cys193 (Kao and Karlin, 1986). In order to identify Asp or Glu residues that may contribute to the negative subsite, we synthesized S-(2 [3H]glycylamidoethyl)dithio-2-pyridine. Purified ACh receptor from Torpedo californica was mildly reduced and reacted with S-(2-[3H]glycylamidoethyl)dithio 2-pyridine. The predominant product was a mixed disulfide between the 3H-N glycylcysteamine moiety and alpha Cys192 or Cys193. In the extended conformation of [3H] N-glycylcysteamine, the distance from the glycyl amino group to the cysteamine thio group is 0.9 nm. Thus, the amino group of disulfide-linked [3H]N glycylcysteamine could react with carboxyls within 0.9 nm of Cys192/Cys193. To promote amide bond formation between the tethered amino group and receptor carboxyls, we added 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide. The predominant sites of amide coupling were on the delta subunit, in CNBr fragment 4 (delta 164-257). This reaction was inhibited by ACh. Only the first 61 residues of delta CNBr 4 are predicted to be extracellular, and there are 11 Asp or Gly residues in this region. One or more of these residues is likely to contribute to the binding of ACh. PMID- 1939276 TI - The nuclear growth hormone receptor binding protein. Antigenic and physicochemical characterization. AB - The mechanisms involved in transcriptional regulation by growth hormone (GH) remain unknown. We report here that GH receptor immunoreactivity can be demonstrated in the nuclei of GH-responsive rat and rabbit tissues at both the light and electron micrograph level using monoclonal antibodies to the receptor extracellular domain. Nuclear staining is heterogeneous and associated with both chromatin and the nuclear membrane. To confirm these observations, nuclei were isolated from rabbit liver by two methods, one involving extensive nonionic detergent washes. Scatchard analysis of nuclear fractions revealed high affinity somatogenic receptor in nuclear membranes, nucleoplasm, and chromatin fractions. A panel of GH receptor monoclonal antibodies was used to further define these nuclear binding sites as being antigenically identical to microsomal receptor in all but one case. In addition, affinity cross-linking experiments showed the somatogenic binding subunit to have a reduced Mr of 67,000, similar to the Mr of the GH binding protein. We propose that the association of a GH binding protein with the nucleus may provide a means whereby GH can regulate the transcription of specific genes either directly or indirectly through nuclear kinase C activation. This speculation is congruent with the recent demonstration of a GH response element by Yoon et al. (Yoon, J. B., Berry, S. A., Seelig, S., and Towle, H. C. (1990) J. Biol. Chem. 265, 19947-19954). PMID- 1939278 TI - A MyoD1-independent muscle-specific enhancer controls the expression of the beta myosin heavy chain gene in skeletal and cardiac muscle cells. AB - The beta-cardiac myosin heavy chain is the major contractile protein expressed in two sarcomeric muscles of distinct embryologic origins, the ventricular myocardium and slow twitch skeletal muscle. Characterization of the cis-acting regulatory sequences of the human and the rat beta-MHC genes established that their expression in these two muscle types is controlled, at least in part, by common mechanisms involving a muscle-specific enhancer. This enhancer consists of distinct but cooperative subelements that interact with muscle-specific nuclear proteins. In contrast to other muscle-specific enhancers, the beta-MHC gene enhancer is unresponsive, directly or indirectly, to the muscle lineage determining and muscle gene-transactivating helix-loop-helix factors MyoD and myogenin. A MyoD-binding site in the rat beta-MHC promoter is not required for transcriptional activity in skeletal and cardiac cells, but is necessary for activation in 10T1/2 and CV1 cells transfected with MyoD. In addition, this element is absent from the human beta-MHC promoter. Thus, MyoD and MyoD-related processes are neither required nor sufficient for the expression of the beta-MHC gene either in cardiac or skeletal muscle cells. These observations provide evidence for the existence of myogenic regulatory programs that precede and/or differ from those governed by known myogenic helix-loop-helix transactivators. PMID- 1939277 TI - The yeast mitochondrial RNA polymerase specificity factor, MTF1, is similar to bacterial sigma factors. AB - We have purified the protein that confers selective promoter recognition on the core subunit of the yeast mitochondrial RNA polymerase. The N-terminal sequence of the 43-kDa specificity factor identified it as the product of the MTF1 gene described by Lisowsky and Michaelis (1988). We confirmed that MTF1 encoded the specificity factor by analyzing extracts from a yeast strain bearing a disruption of the gene. The extracts contained normal levels of core RNA polymerase but lacked selective transcription activity; adding the purified 43-kDa protein restored selective transcription. Comparison of the MTF1 protein sequence to the family of bacterial sigma factors has revealed striking similarity to domains identified with--10 promoter recognition, promoter melting, and holoenzyme stability. PMID- 1939279 TI - Expression, purification, and properties of the flavoprotein domain of cytochrome P-450BM-3. Evidence for the importance of the amino-terminal region for FMN binding. AB - Comparison of the amino acid sequences of several microsomal cytochrome P-450 reductases to the flavoprotein domain (BMR) of cytochrome P-450BM-3 has revealed that this class of flavoproteins contains evolutionarily conserved regions that are important for their interaction with nucleotide substrates and cofactors. In order to understand the properties of BMR, the region encoding this protein, beginning at residue Lys-472 of cytochrome P-450BM-3, was subcloned and expressed in Escherichia coli. The recombinant protein (more than 50% of host-soluble proteins) was purified to homogeneity using conventional purification procedures. BMR (Mr 66,000) showed typical flavoenzyme absorbance spectra, contained FAD and FMN in a stoichiometry of 1:1, and catalyzed reduction of several artificial electron acceptors with rates comparable to those of the microsomal NADPH cytochrome P-450 oxidoreductase. Limited trypsinolysis of BMR, under non denaturing conditions, revealed that the protease removed the NH2-terminal 122 residues. This region was postulated to contain amino acids that are important for FMN binding (Porter, T. D. (1991) Trends Biochem. Sci. 16, 154-158). Consistent with this hypothesis, the major tryptic product of BMR (BMR-52, Mr 52,000) contained only FAD, in an equimolar ratio to the protein. Also, like the FMN-depleted microsomal NADPH-cytochrome P-450 oxidoreductase (Kurzban, G. P., Howarth, J., Palmer, G., and Strobel, H. W. (1990) J. Biol. Chem. 265, 12272 12279), BMR-52 was active for only catalyzing ferricyanide reduction. These data provide strong experimental evidence for a discrete multidomain structure of BMR, as proposed for the membrane-bound reductases, with an amino-terminal FMN binding region and carboxyl-terminal FAD- and NADPH binding regions. Thus, BMR strongly resembles the microsomal cytochrome P-450 reductase and offers an opportunity to better understand the structure-function relationships of this class of flavoproteins. PMID- 1939280 TI - Molecular cloning of rat intestinal mucin. Lack of conservation between mammalian species. AB - We have prepared antisera to deglycosylated rat intestinal mucin and used it to obtain immunoreactive clones from a rat jejunum cDNA library. Four of these clones were sequenced, and all were found to be partial cDNAs that contained 18 base pair tandem repeats characteristic of a mucin. These cDNAs encoded a repetitive peptide with a consensus sequence of TTTPDV. Thus, they bear little resemblance to either of the two human intestinal mucin cDNAs isolated previously (Gum, J. R., Byrd, J. C., Hicks, J. W., Toribara, N. W., Lamport, D. T. A., and Kim, Y. S. (1989) J. Biol. Chem. 264, 6480-6487 and Gum, J. R., Hicks, J. W., Swallow, D. M., Lagace, R. E., Byrd, J. C., Lamport, D. T. A., Siddiki, B., and Kim, Y. S. (1990) Biochem. Biophys. Res. Commun. 171, 407-415). One of these rat mucin clones, designated RMUC 176, was chosen for further analysis. This clone recognized a band of approximately 9 kilobases when used to probe RNA blots. A strong hybridization band was present using rat small intestine and colon RNA but was not detectable when RNA isolated from heart, liver, or kidney was tested. The RMUC 176 clone and the two previously isolated human intestinal mucin cDNA clones were used to probe blots prepared from BamHI-digested DNA of various species. Here, the human probes detected fragments present only in human and chimpanzee DNA, whereas the RMUC 176 clone recognized fragments only in rat and mouse DNA. Thus, the repetitive portions of intestinal mucin genes are apparently not well conserved between phylogenetically distant species. PMID- 1939281 TI - Catalytic subunit of human DNA polymerase alpha overproduced from baculovirus infected insect cells. Structural and enzymological characterization. AB - The human DNA polymerase alpha catalytic polypeptide has been functionally overexpressed by a recombinant baculovirus in insect cells at greater than 1000 fold higher levels than that found in cultured normal human cells. The recombinant polymerase alpha protein is translated from its natural translation start codon under the control of the baculovirus polyhedron promoter producing a protein of 180 kDa, identical in size to that isolated from cultured human cells. This recombinant polymerase alpha is phosphorylated and reactive to a panel of monoclonal antibodies directed against the native polymerase alpha-primase complex and to polyclonal antisera against N- and C-terminal peptides of the polymerase alpha catalytic polypeptide. The recombinant enzyme was immunopurified from insect cells as a single polypeptide. The single subunit recombinant polymerase alpha has no detectable 3'-5' exonuclease activity. The Km for primer template and dNTP, reactivity to inhibitors, N2-(p-n-butylphenyl)-dGTP (BuPdGTP) and aphidicolin, thermosensitivity, and DNA synthetic processivity and fidelity of the recombinant polymerase alpha are identical to that observed with the four subunit polymerase alpha-primase complex immunopurified from cultured human cells. These results strongly suggest that the presence of the other subunits, (the p70 and the two primase subunits, p48 and p58), does not influence kinetic parameters of polymerase alpha catalysis, sensitivity to inhibitors, or DNA synthetic fidelity and processivity. PMID- 1939282 TI - Mitogen-activated 70K S6 kinase. Identification of in vitro 40 S ribosomal S6 phosphorylation sites. AB - Recently we purified and cloned the mitogen/oncogene-activated Mr 70,000 (70K) S6 kinase from the livers of rats treated with cycloheximide (Kozma, S. C., Lane, H. A., Ferrari, S., Luther, H., Siegmann, M., and Thomas, G. (1989) EMBO J. 8, 4125 4132; Kozma, S. C., Ferrari, S., Bassand, P., Siegmann, M., Totty, N., and Thomas, G. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 7365-7369). Prior to determining the ability of this kinase to phosphorylate the same sites observed in S6 in vivo, we established the effects of different cations and autophosphorylation on kinase activity. The results show that the 70K S6 kinase is dependent on Mg2+ for activity and that this requirement cannot be substituted for by Mn2+. Furthermore, 50-fold lower concentrations of Mn2+ block the effect of Mg2+ on the kinase. This effect is not limited to Mn2+ but can be substituted for by a number of cations, with Zn2+ being the most potent inhibitor, IC50 approximately 2 microM. In the presence of optimum Mg2+ concentrations the enzyme incorporates an average of 1.2 mol of phosphate/mol of kinase and an average of 3.7 mol of phosphate/mol of S6. The autophosphorylation reaction appears to be intramolecular and leads to a 25% reduction in kinase activity toward S6. In the case of S6 all of the sites of phosphorylation are found to reside in a 19-amino acid peptide at the carboxyl end of the protein. Four of these sites have been identified as Ser235, Ser236, Ser240, and Ser244, equivalent to four of the five sites previously observed in vivo (Krieg, J., Hofsteenge, J., and Thomas, G. (1988) J. Biol. Chem. 263, 11473-11477). A fifth mole of phosphate is incorporated at low stoichiometry into the peptide, but the amino acid which is phosphorylated cannot be unequivocally assigned. The low level of phosphorylation of the fifth site in vitro is discussed with regard to known results and to a potential three-dimensional model for the carboxyl terminus of S6. PMID- 1939283 TI - Evidence that angiotensin II enhances noradrenaline release from sympathetic nerves in mouse atria by activating protein kinase C. AB - 1. Mouse atria were incubated with [3H]-noradrenaline and the outflow of radioactivity induced by electrical field stimulation (5 Hz, 60 s) was used as an index of noradrenaline release. Angiotensin II (1 x 10(-8) M) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity. 2. Phorbol 12 myristate 13-acetate (0.001-1.0 x 10(-6) M) and phorbol 12, 13-dibutyrate (0.001 1.0 x 10(-6) M), protein kinase C activating phorbol esters, significantly enhanced the S-I outflow of radioactivity. Phorbol dibutyrate produced a greater maximal enhancement of S-I outflow of radioactivity than phorbol myristate acetate. The enhancement of S-I outflow of radioactivity produced by the combination of phorbol dibutyrate (1.0 x 10(-7) M) and phorbol myristate acetate (1.0 x 10(-7) M) was no greater than that produced by phorbol dibutyrate (1.0 x 10(-7) M) alone. The enhancement of S-I outflow of radioactivity produced by phorbol myristate acetate (1.0 x 10(-7) M) was constant whether the tissue was exposed for 15, 45 or 75 min. 3. When angiotensin II (1.0 x 10(-8) M) was present with the maximally effective concentration of phorbol dibutyrate (1.0 x 10(-7) M) it did not increase S-I outflow of radioactivity. 8-bromo-cyclic AMP (9.0 x 10( 5) M) by itself increased the S-I outflow of radioactivity and in the presence of the maximally effective concentration of phorbol dibutyrate the enhancement of S I outflow of radioactivity produced by 8-bromo-cyclic AMP was maintained. 4. A protein kinase inhibitor, K-252a (1.0 x 10(-6) M), did not affect S-I outflow of radioactivity. K-252a significantly reduced the enhancement of S-I outflow of radioactivity produced by both phorbol myristate acetate (0.03 or 0.1 x 10(-6) M) and phorbol dibutyrate (0.01 or 1.0 x 10(-6) M). 5. K-252a (1.0 x 10(-6) M) blocked the enhancement of S-I outflow of radioactivity produced by angiotensin II (1.0 x 10(-8) M) and tetraethylammonium (1.0 x 10(-4) M). 6. These results suggest that angiotensin II receptors may enhance noradrenaline release through the pool of protein kinase C that is activated by phorbol dibutyrate. PMID- 1939284 TI - Regional differences in cholinergic innervation and drug sensitivity in the smooth muscles of pig stomach. AB - 1 To evaluate the regional differences in cholinergic mechanisms in the stomach, innervation and receptor distribution were investigated by isometric tension recording, receptor binding assay and measurement of nerve-related enzyme activity in longitudinal and circular smooth muscle layers isolated from various regions of the pig stomach. 2 The response to transmural nerve stimulation (TMS) varied with the muscle layer and portion of stomach tested. Contraction was predominant in the smooth muscle from the pyloric antrum, relaxation in the corpus region. 3 The contraction to TMS was abolished by atropine (0.1-0.5 microM) and potentiated by physostigmine (1-2 microM). On the other hand, relaxation to TMS was unaffected by a combination of phentolamine and carteolol but was abolished by tetrodotoxin (TTX) (0.67-1.54 microM). In all preparations from various portions, physostigmine unmasked the contraction and atropine revealed the relaxation to TMS. 4 The activity of choline acetyltransferase (ChAT) and cholinesterase (ChE) was higher in longitudinal than in circular muscle layers and was also higher in the fundus than in any other portion. 5 The sensitivity (pD2 value) to acetylcholine (ACh) was higher in the longitudinal than in the circular muscle layers but did not differ largely among different regions of the stomach. The maximum response induced by ACh was also highest in longitudinal muscle of the fundus. In contrast, the population of muscarinic receptors, estimated from [3H]-QNB binding, increased from the fundic to pyloric portions. 6 These results suggest that there are regional differences in the responses to nerve stimulation in pig stomach, which are likely to depend partly on the quantitative differences in cholinergic nerve supply and in the responsiveness to ACh. PMID- 1939285 TI - Imidazole binding sites in rabbit kidney and forebrain membranes. AB - 1. The binding of [3H]-clonidine, [3H]-idazoxan and [3H]-yohimbine to rabbit forebrain and kidney membranes was compared. 2. Yohimbine bound exclusively to adrenergic sites, idazoxan to non-adrenergic sites and clonidine to both non adrenergic and adrenergic sites. 3. Differences were observed between the ligands not only in binding at adrenergic and non-adrenergic sites but also between the non-adrenergic binding of [3H]-clonidine and [3H]-idazoxan. 4. However, no tissue specific differences were found. PMID- 1939287 TI - Fertility levels and trends in Arsi and Shoa regions of Central Ethiopia. AB - Levels and trends of fertility in the Arsi and Shoa regions of Central Ethiopia are examined, using data from the 1986 Population, Health and Nutrition baseline survey of the Ministry of Health of Ethiopia. The population has high fertility. Total fertility of six children per woman in the late 1960s increased to eight children per woman in the early 1980s, then declined to seven children per woman in the mid-1980s. Urban fertility declined by a substantial amount during the 15 years before the survey while rural fertility increased during the same period. The implications of high fertility are considered. PMID- 1939286 TI - Predicting alcohol use by adolescent males. AB - An attempt was made to predict alcohol use among 101 American white boys aged 13 16. The model combined genetic and social variables. The analysis revealed evidence of a genotype-environment interaction and thus the use of either the biological or social variables alone poorly predicts alcohol use. PMID- 1939288 TI - Biosocial correlates of stature in a 16-year-old British cohort. AB - Analyses of the height variation of 16-year-old members of the British National Child Development Study revealed a number of biological and social variables which associated with stature. After multiple regression analyses only eight variables, namely social class, family size, tenure (owner occupied or one of several types of rented home), crowding status, number of children sleeping in the bed, region of the country, sex of child, and pubic hair rating, remained significant. The total variation explained by these biosocial variables was 37.5%. PMID- 1939289 TI - Reaction times and intelligence: a comparison of Japanese and British children. AB - Japanese and British 9-year-old children were compared on the standard progressive matrices and twelve reaction time parameters providing measures of simple and complex decision times, movement times and variabilities. The mean of the Japanese children on the progressive matrices exceeded that of the British children by 0.65 SD units and on the decision times component of reaction times by 0.50 SD units, suggesting that the high Japanese mean on psychometric intelligence is largely explicable in terms of the more efficient processing of information at the neurological level. Japanese children also showed faster movement times but, contrary to expectation, had greater variabilities than British children. PMID- 1939290 TI - Birthweight and sociobiological factors in Ilorin, Nigeria. AB - Social and biological factors influencing birthweight of 3053 Ilorin babies were studied. The mean birth weights were 2.998 kg +/- 0.133 (SD) for males and 2.932 kg +/- 0.154 (SD) for females. Multiple regression analysis showed that maternal weight, height, age, education and ethnicity, and child's sex, significantly affected birthweight of infants. Some quadratic and interaction terms also contributed significantly to the prediction of birthweight. The strategies to control the incidence of low birth weight are discussed. PMID- 1939291 TI - Socioeconomic, demographic and environmental determinants of infant mortality in Nepal. AB - The Nepal Fertility and Family Planning Survey of 1986 demonstrated that demographic variables, previous birth interval and survival of preceding child, still predominated as determinants of infant mortality, particularly in rural areas of Nepal. However, in urban Nepal, where the level of socioeconomic development is higher, an environmental variable, along with previous birth interval and survival of preceding child emerges as important in determining infant mortality. Separate policy measures for child survival prospects in rural and urban Nepal are suggested. PMID- 1939292 TI - Effect of education and household characteristics on infant and child mortality in urban Nepal. AB - Infant and child mortality differentials are analysed by education of parents and other family members, access to toilet, electricity and source of drinking water in urban Nepal, using data from the Nepal Fertility and Family Planning Survey, 1986. The analyses showed significant effects of education, access to toilet and electricity in lowering infant and child mortality. Access to toilet and electricity are proxies for household socioeconomic status which suggests that education and household resources are complementary in lowering the infant and child mortality. PMID- 1939293 TI - Birth spacing and infant mortality: evidence for eighteenth and nineteenth century German villages. AB - Data from an historical population in which fertility control was minimal and modern health services were mostly unavailable are used to show that there appears to have been a strong association between previous birth interval length and infant mortality, especially when the previous child survived. Although only imperfect proxies for breast-feeding practices and other potentially confounding factors are available for this population, the results suggest that the association between previous interval length and infant mortality in this population is not solely, or primarily, a function of differences in breast feeding behaviour or socioeconomic status. Other factors, e.g. maternal depletion or sibling competition, are more likely to explain the observed association. PMID- 1939294 TI - Infecundity and subfertility among the rural population of Ethiopia. AB - A 1980-81 survey of the rural population of Ethiopia found high levels of infecundity and subfertility, although there was considerable variation by region, ethnicity and age of women. Higher levels of infecundity were geographically concentrated in a broad belt that ran from the south and south west of the country, across to the north-east. The analyses suggest that infecundity is influenced by ecological factors, more than by ethnicity. PMID- 1939295 TI - Birth weight and other determinants of infant and child mortality in three provinces of China. AB - Information on levels, trends and determinants of infant and child mortality was available from the 1985 In-depth Fertility Survey which was conducted in three provinces of China. Mortality of children below age 5 varied from 49 per 1000 live births in Shaanxi to 20 in Shanghai in 1980-85 and has declined substantially since 1960, from 206 in Shaanxi and 66 in Shanghai. Male mortality was considerably higher than female mortality in the neonatal and post-neonatal period, and at ages 1-5 years. Birth weight, place of residence and mother's education were found to be important determinants of mortality; age of mother and parity were less important. PMID- 1939296 TI - Family environment and cognitive correlates of young adults' social status attainment: ethnic group differences. AB - A longitudinal sample of 21-year-old Australians from Anglo-Australian, Greek and Southern Italian families was used to examine relationships of children's cognitive performance, family learning environments, adolescents' perceptions of family learning contexts, and measures of young adults' social status attainment. Generally, the findings using a regression approach indicated that there were ethnic group differences in the relations between parents' academic socialisation, children's cognitive performance, and measures of young adults' social status attainment. The results also showed that in each ethnic group, adolescents' perceptions of parents' support for learning had strong associations with young adults' status attainment. PMID- 1939297 TI - Matriarchy, polyandry, and fertility amongst the Mosuos in China. AB - A survey of 232 households of the Mosuo minority group in Yunnan Province, People's Republic of China, suggested that polyandrous matriarchy did not raise the birth rate per household, but lowered the community birth rate by restricting many women's chances of marrying. The results imply that tolerance by the national government of polyandry within certain minority groups (e.g. Mosuos and Tibetans) will not prevent but may aid the attainment of zero population growth by China in the twenty-first century. PMID- 1939298 TI - Weak direct current accelerates split-thickness graft healing on tangentially excised second-degree burns. AB - We have examined the effects of direct current (DC) conducted through silver nylon dressings on the healing time and morphologic maturation of split-thickness grafts placed on tangentially excised deep partial-thickness burn wounds. Male guinea pigs (n = 120) were used as the experimental hosts. The DC-treated animals required 2 days for complete revascularization of their grafts; control animals required 7 days (p less than 0.01). The DC-treated animals had increased epithelial proliferation at the graft-wound interface as compared with controls (p less than 0.01). Grafts from DC-treated animals were firmly adherent within 4 days, whereas graft adherence in controls was weak before 7 days after grafting. At 3 months after grafting, control animal grafts had mild contraction with moderate hair loss and thick subepidermal fibrosis; the grafts in DC-treated animals expanded with the growth of the animals and had abundant hair growth and significantly reduced dermal fibrosis (p less than 0.01). PMID- 1939299 TI - Causes of colonization of autografted burn wounds. AB - The progression of autograft colonization to infection presents significant problems in the care of grafted burn wounds. To determine whether graft colonization arises from self-contamination or from some exogenous source, we characterized pregraft and graft Candida albicans isolates through serotyping and biotyping (Leicester system) and Pseudomonas aeruginosa isolates through serotyping (Japan Pseudomonas aeruginosa Society system). In 21 of 24 patients, the serotype/biotype of the graft isolate was the same as the serotype/biotype of a C. albicans strain previously isolated from the same patient. Fifteen of 16 P. aeruginosa graft contaminants also showed the same serotype as that in a pregraft isolate. Therefore, whereas it has long been surmised that the grafts of patients with burns are self-colonized, this study provides definite data showing that most C. albicans and P. aeruginosa autograft isolates are indeed self contaminants. PMID- 1939300 TI - Elastase and alpha 1-protease inhibitor in burn wound exudates. AB - By degrading antithrombin III, polymorphonuclear neutrophil (PMN) elastase can become a procoagulant. Because intravascular coagulation may accompany severe burn injury, this study examined burn wound exudates for PMN elastase and its physiologic inhibitor, plasma alpha 1-protease inhibitor (alpha 1-PI), as a step in evaluating their contributions to coagulopathy in patients with burns. Each of the nine exudates examined were inhibitory for PMN elastase. Chromatographic characterization of the inhibitor indicated that it was alpha 1-PI; its elution volume for four exudates was identical to that of pure alpha 1-PI. Confirmation of the inhibitor's identity was achieved by reaction of anti-alpha 1-PI antibody with each exudate and with inhibitory chromatographic fractions of exudates with the most inhibitory activity. Inhibitor potency, determined from dose-response curves against a standard PMN elastase activity, varied twentyfold among exudates. Only one exudate had catalytic activity with the PMN elastase substrate. Although this enzyme had elastase-like properties, it appeared to differ from PMN elastase. The presence of alpha 1-PI in the wound exudate suggests that this inhibitor may act to diminish fibrin formation from the level that might otherwise have been seen if excess elastase were free to degrade antithrombin III. PMID- 1939301 TI - Antigenic cross-reactivity between media supplements for cultured keratinocyte grafts. AB - Patients who were grafted with cultured human keratinocytes have been shown to make antibodies to the xenogeneic proteins, which supplement the culture media. An immune response to these antigens may lead to late graft loss or accelerated rejection of subsequent cultured keratinocyte grafts. Methods to eliminate this potential problem include growing cells in a serum-free medium with bovine pituitary extract as a serum substitute. To determine whether bovine pituitary extract would be subject to an immune response similar to that which is evoked by fetal bovine serum, we investigated their antigenic cross-reactivity. When compared by sodium dodecylsulfate-polyacrylamide gel electrophoresis, considerable similarity was identified between the two supplements. Immunostaining with antibodies to both bovine pituitary extract and fetal bovine serum confirmed antigenic cross-reactivity. Inhibitory enzyme-linked immunosorbent assay studies demonstrated specific cross-reactivity that ranged from 60% to 68%. When tested for antibody cross-reactivity to bovine pituitary extract, serum samples from five patients who were receiving human-keratinocyte grafts that were grown in fetal bovine serum-supplemented media and that exhibited a positive antibody titer to fetal bovine serum showed cross-reactivity that ranged from 30% to 141%. Bovine pituitary extract contains proteins that cross-react with fetal bovine serum. Human keratinocytes that are cultured in media that is supplemented with bovine pituitary extract would therefore be subject to an immune response similar to that which is evoked by human keratinocytes that have been cultured in fetal bovine serum. PMID- 1939303 TI - Classifying patients with burns for hospital reimbursement: diagnosis-related groups and modifications for severity. AB - This study was designed to evaluate the relative severity and resource consumption of hospitalized patients with burns in a national cross section of hospitals, both with and without burn centers. We investigated to determine whether clinical variables or severity of illness measures not recorded in the Uniform Hospital Discharge Data Set are significant in explaining variation in length of stay, total cost, and mortality for patients with burns. The ability of the six burn diagnosis-related groups (DRGs) to explain variation in patients' length of stay was 20% and their ability to predict total costs was 24%. For the same patient population, the explanatory power of the DRGs improved to 54% for length of stay and 44% for costs when these variables were adjusted by the Severity of Illness Index. We also investigated whether hospitals with burn centers treated a more severely ill population of patients with burns than did hospitals without such centers. Significantly higher levels of severely ill patients with burns (p less than or equal to 0.0001) were found at burn center hospitals. Other patients or treatment variables, combined with a case-mix severity measure, were evaluated for their ability to further increase the explanatory power of DRGs. We also discuss here the use of the study results for reevaluating reimbursement policy. PMID- 1939302 TI - Endoscopic laser flowmetry: a valid method for detection and quantitative analysis of inhalation injury. AB - Hyperemia of the tracheobronchial area is a major sign of inhalation injury. However, this is usually a qualitative symptom, without quantitative measurement. We have developed a technique to diagnose inhalation injury and to analyze damaged areas quantitatively with laser-doppler flowmetry. In chronically instrumented sheep (N = 10), the tissue blood flow in the wall of second generation bronchi was determined with an endoscopic flowmeter probe. After baseline data had been obtained, the right lung was exposed to smoke in seven animals. Three sham-smoked animals underwent the same procedure, but without actual smoke. The bronchial blood flow was measured again 30 minutes after insufflation in both groups. Inhalation injury caused a significant increase in flow, from 35.1 +/- 2.6 to 51.7 +/- 2.1 ml/min.100 gm tissue in the airway of the smoked lungs but not in the control lungs. This increase correlated with an increase in the carboxyhemoglobin level (r = 0.87). The sham-smoked animals showed no change in bronchial blood flow. A valid technique for diagnosing inhalation injury in the early phase and a quantitative analysis of injured areas has been demonstrated. PMID- 1939305 TI - Salvage of ear cartilage in patients with acute full-thickness burns. AB - Three cases in which the temporoparietal fascial flap was used to salvage denuded ear cartilage during the acute period after burn injury are reported. Patients' burns ranged from 30% to 75% total body surface area. The full-thickness burn was acutely excised, exposing the auricular cartilage. The temporoparietal facial flap was elevated and wrapped around the cartilage. The flap was then covered with a split-thickness skin graft. All flaps and skin grafts survived. Additional reconstructive procedures have been performed on two of the patients and are planned for the third. PMID- 1939304 TI - The relationship of patient stress to burn injury. AB - The stress of burn injury can have an especially profound psychologic effect on individuals with recent histories of stress life events. A review of the literature reveals a model for this effect and documents the possibility of burn prone patients, a concept that may explain the high number of patients with burns who also report a high level of stress before injury. This study was designed to assess the proportion of patients with burns reporting previous stress and to assess the relationship of this stress to burn injury and its exacerbating effects. A definite correlation between previous stress and burn injury was found, indicating that many patients with burns may have been in a vulnerable state at injury. Since such vulnerable patients will show a more severe reaction and more serious level of psychologic dysfunction than the seriousness of their injuries might indicate, their identification would have decided benefits in their psychologic rehabilitation. PMID- 1939306 TI - A desensitization process to facilitate first visits between burn-scarred parents and young children. AB - The young children of patients with severe burns need particular attention in preparation for their first visit with their parent. A desensitization process was developed and proven to be quite effective for both child and parent. PMID- 1939307 TI - Topical treatment of toxic epidermal necrolysis with Iodoplex. AB - Toxic epidermal necrolysis (TEN) is characterized by extensive exfoliation of the epidermis, mucosal ulcerations and fever, after a recent intake of a new drug. TEN developed in an 8-year-old girl after she ingested sulfonamides and sustained skin injuries of 90% total body surface area. In addition to her critical care management, local treatment consisted of Iodoplex cream (Biosearch Laboratories, Haifa, Israel), a long-acting antimicrobial agent from which iodine is slowly released over 48 hours. Healing was observed within 8 to 17 days after initial application. Iodoplex cream is an additional topical agent for the local treatment of TEN when porcine heterografts or allografts might not be feasible. PMID- 1939308 TI - An anesthetic technique to fabricate a pressure mask for controlling scar formation from facial burns. AB - An anesthetic technique, involving nasotracheal intubation, after mask induction with halothane, nitrous oxide, and oxygen, is described for use during fabrication of a contoured facial pressure mask. Rationale and benefits are discussed, and particular emphasis is placed on the potential problems of the commonly used ketamine-based technique. PMID- 1939309 TI - Silicone patches as a supplement for pressure therapy to control hypertrophic scarring. PMID- 1939310 TI - Use and efficacy of a nutrition protocol for patients with burns in intensive care. AB - The University of Michigan Burn Center uses a protocol to standardize the assessment, initiation, and monitoring of nutritional support for patients with burns of greater than 30% total body surface area (TBSA). Six patients with 20% to 80% TBSA burns were followed for 3 weeks to determine the effect of the protocol on the assessment, initiation, monitoring, and adequacy of nutritional support. The protocol calls for resting energy expenditure (REE) measurement within 24 hours of injury, to be repeated 3 times per week, for assessment of caloric requirements. Patients experienced an average delay before first REE measurement of 3 days after burn injury because measurements were unavailable on weekends and surgical days. REE measurements were used to determine caloric requirements and to tailor nutritional support to fluctuating metabolic needs. In four of the six patients a Dobhoff feeding tube (Biosearch Medical Products, Inc., Somerville, N.J.) was placed in the small bowel and enteral nutrition was initiated within 24 hours of admission, as outlined in the protocol. Two patients received concurrent parenteral nutrition because of difficulty in placing the Dobhoff feeding tube when fluoroscopy was not available. The three patients receiving nutrition solely through enteral feeding had achieved 100% of their caloric requirements by day 2, 4, and greater than 7 days after injury, respectively. Overall, the six patients received enterally an average of 75% of their caloric requirements. The major reason for inadequate enteral support was interruption of tube feedings because of tube dislodgment or multiple surgical procedures. The protocol used weekly measurements of total iron-binding capacity and prealbumin level s parameters of nutritional support.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939311 TI - Research priorities for burn nursing: patient, nurse, and burn prevention education. AB - Fifteen of the 101 research questions that were assigned priorities in the Burn Nursing Delphi study by Marvin et al. (Marvin JA, Carrougher GJ, Bayley EW, Weber B, Knighton J, Rutan RL. Burn nursing Delphi study: setting research priorities. J BURN CARE REHABIL 1991;12:190-7) addressed education from the perspectives of patients, their families, and burn nurses; the study also addressed the issue of burn prevention education. Questions concerning patient education were assigned the highest priority in this education subgroup with respect to the potential for research that would have an impact on patient welfare. The question that rated highest as a priority for its potential impact on the profession of burn nursing addressed the core competencies needed for safe and effective burn nursing practice. Prevention education was generally found to be a low priority in the Delphi study. Many of the questions in the education subgroup can best be answered by comparative or experimental studies designed to explain and predict the effects of various teaching strategies on behavioral outcomes. Research on patient, nurse, and burn prevention education provides a fertile ground for nurse researchers and an opportunity to contribute knowledge of vital importance to clinicians, educators, managers, and the public. PMID- 1939312 TI - Torque and the quantification of joint stiffness. PMID- 1939313 TI - What is the place of pulmonary embolectomy today? AB - From 1.1970 to 31.12.1989, 134 patients with pulmonary embolism were treated by pulmonary embolectomy (74 women and 60 men) of mean age 55 years (23-78 years); 93 (69%) of these patients developed embolism during the postoperative period following surgery for another condition. In 12 cases the embolectomy was performed without circulatory assistance by a modified Trendelenburg operation after an average delay time of 2 hours. In 122 cases, extracorporeal circulation (ECC) was used, preceded in 64 cases, by a femoral-femoral bypass (the average delay interval of operation being 16.9 hours). At operation, 23 patients were in complete circulatory failure needing external cardiac massage, 34 were in cardiogenic shock with systolic arterial pressures (SAP) less than 60 mmHg, 42 maintained their arterial pressure between 60 and 100 mmHg, and only 35 were seen with SAP higher than 100 mmHg under vasopressive drugs. No haemodynamic and angiographic investigations could be undertaken in 31 patients because of their dramatic clinical state. In the other 103 patients who had invasive angiographic investigations performed the pulmonary bed was obstructed from 65% to 90% (mean 79.4%) according to Miller's index. The mean arterial pulmonary pressure was 51.2 mmHg. The survival rate at the 30th postoperative day showed 113 patients were alive (84.3%) with 7 among the 12 operated by the Trendelenburg's modified method and 106 among the 122 operated under ECC. The main causes of the 21 deaths were: peroperative 8, neurological 4, cardiac 4, respiratory 1, recurrent embolism 1, acute thrombosis of the IVC 1. Our results of pulmonary embolectomy can be compared favorably to those obtained by thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939314 TI - New technique for infusion of cardioplegic solution in aortic valve incompetence. AB - Direct coronary cannulation for induction of cardioplegia in patients with aortic valve incompetence may result in ostial stenosis. In order to circumvent this problem, a technique by which the valve was made competent by suturing the cusps together has been recently applied. Thus, an effective aortic cardioplegic infusion could be accomplished. PMID- 1939315 TI - A comparative study of the St. Jude Medical and Bjork-Shiley convexo-concave prostheses in isolated valve replacement. AB - This is a study of 199 consecutive patients who survived isolated mitral or aortic valve replacement with a Bjork-Shiley (B-S) or St. Jude Medical (SJM) prostheses. Mean follow-up was 36 months. Preoperative status was similar for both groups (B-S or SMJ). Five year survival rates for mitral valve replacement (MVR) were 91% for B-S and SJM, and for aortic valve replacement (AVR) 96% vs 91% for SJM (p less than 0.06). Linearized incidence of thromboembolism in MVR was 5.62% patient year for BS and 5.23% patient year for SJM (p = NS). Classical risk factors for thromboembolism were evaluated on a univariate analysis: no single risk factor was identified. Only the association of two or more was possibly significant. The presence of inadequate anticoagulation (prothrombin index greater than 50%) was the main risk factor for thromboembolism, as the incidence rate was 19% per patient year when poorly anticoagulated versus 4.6% per patient year incidence in the whole series (p less than 0.01). PMID- 1939316 TI - The problems of valve surgery in a developing country. AB - The management of young patients with valvular heart disease is a difficult problem in developing countries. At our Institution, 765 valves were operated upon in 523 patients over a period of two years. Rheumatic etiology was seen in 70% of the valves and 60% of all the valves were repaired. The hospital mortality and morbidity in the form of thromboembolic episodes were less in the repair group; 35 valves in 26 patients had to be reoperated upon for instability of the primary repair. Despite this high and early reoperation rate in the repair group and considering the higher mortality plus the problems of anticoagulation and limited durability of bioprostheses in the replacement group, conservation of the patient's own valve remains a better alternative in the long-term. PMID- 1939318 TI - Ligation in adult persistent ductus arteriosus. AB - Seventy one patients with a persistent ductus arteriosus were operated upon at the Cardiovascular Unit in Gulhane Military Medical Academy. The mean age of these cases was 24 years. Twenty five patients (35%) were asymptomatic. The average pulmonary artery systolic pressure was 50 +/- 22 mmHg. In the majority of the cases the ductus was ligated (91.5%), but 6 of the cases were treated by division (8.5%). Early and late complications or mortality were not encountered. In this study 71 cases are reviewed: the preoperative cardiac catheterization and the operative findings are studied in relation to the surgical procedures used. Ligation is a simple, quick and effective surgical treatment for persistent ductus arteriosus in adults. PMID- 1939317 TI - Prevention of perioperative neurological dysfunction. A six year perspective of cardiac surgery. AB - Neurological dysfunction following cardiac surgical procedures is now well recognized. In order to minimise this serious complication, we instituted various protocols related to the potential causes of perioperative stroke such as: (1) components and use of the heart-lung machine; (2) air embolization; (3) intrinsic cerebro-vascular disease; (4) atheroemboli from the ascending aorta and (5) clot emboli from the left ventricle. We employed certain methods of operation of the heart-lung machine, air evacuation manoeuvres and a pharmacological brain protection protocol. These protocols were applied in a series of 1487 consecutive cardiac surgical procedures performed between 1984 and 1989; 127 patients died (8.54% mortality) and 16 patients (1.08%) suffered major neurological syndromes. Among the latter patients, 4 distinct groups were identified. Group A consisted of 6 patients who remained unresponsive after operation. In group B were 6 patients who awakened after operation but had clinical evidence of focal cerebral infarction. Group C included 3 patients who were initially intact neurologically but in whom neurological deficits developed later. Group D contained 1 patient who had severe mental aberration but no focal neurological deficits. Causative factors, including atheromatous embolism, perioperative hypotension and air embolism, were suspected in 12 of these 16 patients (75%) in groups A, B and C. The outcome was poor for unresponsive patients and 9 out of the 16 died or remained comatose (56.6%). PMID- 1939319 TI - Correction of tetralogy of Fallot accompanied by malignant hyperthermia. Case report. AB - A 5-year-old girl susceptible to malignant hyperthermia underwent total repair of tetralogy of Fallot. The initial operation was canceled because of abrupt hyperthermia and metabolic acidosis of unknown cause. Dantrolene was given orally as preoperative treatment and administered intermittently during surgery. Postoperative hyperthermic crisis was successfully treated with intravenous dantrolene combined with surface cooling, gastric tube irrigation with cold saline, and alcohol vaporization. PMID- 1939321 TI - Blood cyst originating from tricuspid septal leaflet. AB - Successful removal of a blood cyst of the tricuspid valve in a 34 years old man is reported. The rarity of this cyst in an adult and diagnostic clues are discussed. PMID- 1939320 TI - Post traumatic tricuspid insufficiency: when to intervene? AB - Isolated post traumatic tricuspid insufficiency is a rare entity with an increasing incidence. It is associated with insidious yet unequivocal hemodynamic alterations leading to severe incapacity. Early surgery rather than medical treatment is the therapeutic modality of choice. PMID- 1939322 TI - Carotid surgery. Is regional anesthesia always appropriate? AB - We retrospectively studied a series of 385 carotid endarterectomies performed either under general anesthesia (242) or under local anesthesia (145) to compare the peri-operative mortality and morbidity rate and to identify factors which may influence the choice of anesthesia. The rate of transient ischaemic attacks (TIA), stroke, death, combined mortality, severe neurological and cardiac morbidity were not statistically different. Under general anesthesia, more shunts were inserted (17% versus 7%, p less than 0.05) and more myocardial infarctions occurred (5% versus 0%, p less than 0.05). However, more strokes due to technical imperfection were seen under regional anesthesia. We concluded that regional anesthesia is more appropriate in patients with coronary artery disease and in patients at risk of intolerance to cross clamping. General anesthesia is more appropriate in poorly cooperative patients or in those with unfavorable operative conditions. PMID- 1939323 TI - Severe injuries resulting from operations for thoracic outlet syndrome: can they be avoided? AB - Surgery for thoracic outlet syndrome (TOS) is claimed to have a low risk of severe complications. To re-evaluate this, a questionnaire was sent out to the French vascular surgical community. There were 66 replies. While some surgeons had operated on several hundred patients without any severe complications, others had experienced rare but dramatic complications including wounds or thrombosis of the axillary artery, vein injuries or thrombosis, transient or definitive paralysis of the brachial plexus, long thoracic or phrenic nerves, hemothorax, and chylothorax. Two resulted in the death of young patients. The results of the present study, as well as rare reports in the literature, demonstrate that these complications may occur even with experienced surgeons using either the supraclavicular or transaxillary approaches. We conclude that: (1) operation for TOS should be considered only when the diagnosis is certain and when operative decompression is the sole solution; (2) the choice of an adequate approach, good vision during operation, and meticulous technique are all mandatory for full security. Surgical guidelines are suggested. PMID- 1939324 TI - Subclavian artery stenosis: hemodynamic aspects and surgical outcome. AB - Ninety seven patients (mean age: 58 years) with lesions involving the subclavian artery were studied to determine the relationship between clinical symptoms, angiographic lesions and Doppler-detected hemodynamic disorders. Ninety patients had vertebro-basilar insufficiency (VBI) and 7 had hemispheric manifestations or upper limb ischemia. Of the 105 lesions of the subclavian artery, we observed 76 stenoses greater than 50% and 29 complete occlusions. Thirty seven patients presented a unilateral subclavian lesion and 63 multiple lesions. Doppler examination of the vertebral artery including an upper limb hyperaemic test allowed classification of the patients into three stages: stage 1 "pre-subclavian steal" (35 patients): sudden decrease in the systolic vertebral flow with complete interruption during hyperaemia; stage 2 "intermittent subclavian steal" (18 patients): transient inversion of vertebral during systole with permanent inversion for 1 or 2 minutes after hyperaemia; stage 3 "permanent subclavian steal" (33 patients): complete inversion of the vertebral flow without diastolic flow and increase of flow during hyperaemia. The clinical, hemodynamic and angiographic findings were compared. In stage 1, 65.7% of the patients presented severe VBI (at least two signs) and 66% had a 50 to 70% stenosis of the subclavian artery. In stage 2, 66.6% of the patients presented severe VBI and 78% had a 75 to 95% stenosis. In stage 3, 72.7% of the patients had severe VBI and 73% had either subtotal or complete occlusion of the subclavian artery. There was no correlation between the severity of VBI and the hemodynamic stages but a strong correlation between the hemodynamic grades and the anatomical lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939325 TI - Traumatic lesions of the thoracic aorta. A report of 73 cases. AB - In a 24 year period we treated 73 traumatic lesions of the thoracic aorta; 36 of these were acute ruptures and 37 post traumatic pseudo-aneurysms. All these cases were associated with violent, sudden deceleration and in 68 instances the cause of this was a traffic accident. Fifty two patients (70%) had severe associated lesions involving the cranium, abdomen, thorax or leg fractures and dislocations but in 5 patients the aortic rupture was the only injury observed. Thirty four patients with acute aortic lesions were operated upon; 30 with extracorporeal circulatory assistance (CA) and 4 with aortic cross clamping alone. Twenty one were repaired by direct suture, 13 by prosthetic graft interposition and there were 8 deaths (23.5%) and one case of post-operative paraplegia. Thirty six traumatic aneurysms were operated upon; 34 with CA and 2 with cross clamping. Only two were repaired by direct suture, 5 by prosthetic angioplasty and 29 required prosthetic interposition grafts; there were no deaths or paraplegias in this group. Aortic rupture demands early diagnosis and immediate surgery. Associated abdominal injuries are easily missed and therefore exploratory laparotomy should be considered after every acute aortic repair. PMID- 1939326 TI - Outcome of asymptomatic cervical bruits in a veteran population. AB - The potential risk of stroke in patients with a localized asymptomatic cervical bruit continues to be a source of debate. We identified 273 patients with 374 asymptomatic mid-cervical bruits. Using Doppler with spectral analysis, the internal carotid artery (ICA) was stratified into one of three groups; greater than or less than 75% cross section area stenosis, or occlusion. Each carotid artery was evaluated for progression of stenosis and occurrence of neurologic events (TIA's and strokes). During an average follow-up of 29.6 months, 26 neurologic events (10 strokes, 16 TIA's) occurred ipsilateral to the carotid bruits. Most asymptomatic bruits (308/374; 82%) were associated with carotid arteries having less than 75% stenosis and the risk of stroke from those arteries remaining at less than 75% stenosis (254/308) was 1.5%. However, progression to greater than 75% stenosis or occlusion as determined at the most recent noninvasive examination (54/308) was associated with a significant risk for stroke (7.4%; p less than 0.001). Progression to occlusion in the total population was highly significant for the risk of developing stroke (4 out of 19; p less than 0.001). PMID- 1939327 TI - Surgery for abdominal aortic aneurysms. A survey of 656 patients. AB - Between 1979 and 1988, 656 patients were operated upon for abdominal aortic aneurysm. Elective operation was performed in 287 patients (44%) and acute operation in 369 patients. A ruptured aneurysm was found in 218 patients (33%). Patients with arteriosclerotic heart disease, hypertension, impaired renal function or chronic pulmonary disease showed an increased perioperative mortality. Development of postoperative cardiac and renal complications could not be related to previous cardiac or renal diseases. The major postoperative complications were renal failure in 81 patients (12%), pulmonary insufficiency in 77 patients (11%) and cardiac complications in 96 patients (13%). Failure of one or more organs occurred in 153 patients (23%) and the mortality rate for patients with multiorgan failure was 68%. Complications leading to reoperation occurred in 93 patients (14%). The perioperative mortality was 18.8%. The mortality for elective cases was 4.8%, for symptomatic cases 17.2% and 37% for ruptured aneurysms. The five-year survival rate was 48% for ruptured aneurysms, 70% for symptomatic cases and 75% for elective cases. After six months the life expectancy in these three groups of patients were identical and comparable to the expected survival for a sex and age matched control population. PMID- 1939328 TI - Acute aortic occlusion presenting with lower limb paralysis. AB - In a two year period eight patients have presented with acute aortic occlusion and a poor outcome in seven. Initial failure to diagnose aortic occlusion, with a mean delay from presentation to diagnosis of 24 hours, was mainly responsible. All patients had varying degrees of paralysis on presentation which misled clinicians although other findings of acute ischaemia (pain, absent pulses, colour change and anaesthesia) were always present. Two patients were initially referred to a neurologist, another to a neurosurgeon, and the fourth to an orthopaedic surgeon. Even after diagnosis had been established, the need for urgent revascularization was not always recognized, the mean time from diagnosis to revascularization being 13 hours. Unnecessary aortography contributed to this delay in four patients. In two patients operative treatment was not undertaken while six were treated operatively by: aortic bifurcation graft (3), aortic thromboendarterectomy and femoropopliteal bypass (1), open aortic embolectomy (1) and bilateral femoral embolectomy (1). The causes of aortic occlusion were thrombosis of an atherosclerotic aorta (5), thrombosis of an aneurysm (2) and embolism (1). In the latter patient, the heparin induced thrombocytopenia syndrome (HITS) was primarily responsible. The outcomes in the eight patients were death (5), paraplegia (1), amputation (1), and uncomplicated recovery (1). The single patient who made an uncomplicated recovery had the shortest delay from presentation to revascularization of only 2 1/4 hours. Acute aortic occlusion rivals aortic rupture as a vascular emergency and demands immediate operative intervention. PMID- 1939329 TI - The effect of intraabdominal pressure and saline infusion on abdominal aortic hemorrhage. AB - Blood loss, survival, and hemodynamics were monitored for 1 hour or until death in 30 anesthetized pigs with a 0.5 cm abdominal aortic laceration. Eight animals (Group I) had no treatment; 7 animals (Group IA) had saline infusion at a maximum rate of 200 mls/min to maintain carotid artery pressure (CP); 8 animals (Group II) had intraabdominal pressure increased to 60 torr by pneumatic antishock garment (PASG) inflation; and 7 animals (Group IIA) had PASG inflation with saline infusion to maintain CP. Groups I and IA survived 9.5 +/- 4.2 minutes and 28.0 +/- 5.5 minutes, respectively (p less than 0.05). Groups II and IIA survived the 1 hour. Saline infusion (5400 +/- 120 mls in Group IA and 535 +/- 180 mls in Group IIA, p less than 0.05) increased blood loss without PASG inflation (1289 +/ 49 mls in Group I vs. 4840 +/- 1350 mls in Group IA, p less than 0.05) as well as with PASG inflation (438 +/- 64 mls in Group II vs. 1235 +/- 68 mls in Group IIA, p less than 0.05). CP could not be maintained in spite of saline infusion in Group IA but in Group IIA CP was maintained with saline infusion. In an otherwise fatal abdominal aortic laceration, increasing intraabdominal pressure improves survival and decreases hemorrhage. While saline infusion may prolong survival it increases hemorrhage both in the presence and absence of increased intraabdominal pressure. PMID- 1939330 TI - Deterioration of PTFE-prostheses wall. A SEM study. AB - Specimens of long-term femoro-popliteal ePTFE bypass implants were examined by means of scanning electron microscopy in order to analyze the structure of the prosthetic wall. Twelve months after implantation, the structure of the ePTFE wall was inhomogeneous with a widening of the micropores, and both compressed and ruptured fibrils. The most significant disturbances were observed in the knee joint area. Our results suggest that deterioration of the prosthetic wall is possible and indicate the necessity for a wrap to protect against aneurysm formation, as well as an external supportive device to prevent the graft from bending. PMID- 1939331 TI - Studies of reperfusion injury in skeletal muscle: preserved cellular viability after extended periods of warm ischemia. AB - Four hours of complete normothermic ischemia in the rat hindlimb has been thought to produce extensive and irreversible damage and no possibility of salvage by reperfusion. This study tests the hypothesis that, in contrast to conventional wisdom, the cellular integrity is preserved after 4 hours of complete warm ischemia and control of the initial reperfusion can restore immediate contractility in these limbs. Ninety-two rat hindlimbs were isolated and 26 of the 92 did not undergo ischemia or reperfusion and served as controls. Sixty-six limbs were subjected to 4 hours of complete warm ischemia; of those 34 were assessed after the ischemic period without reperfusion and 32 were reperfused after the ischemic period. Nineteen hindlimbs were reperfused with Krebs Henseleit buffer at a pressure of 100 mmHg to simulate embolectomy (uncontrolled reperfusion). In 13 legs a modified reperfusate at a pressure of 60 mmHg was used during the initial 30 minutes followed by an additional 30 minutes of reperfusion with 100 mmHg using Krebs-Henseleit buffer (controlled reperfusion). At the end of each experimental protocol, limbs were assessed by the following methods: muscle contraction, water content, volume, high energy phosphate content, muscle pH, effluent pH, mitochondrial function, ultrastructure, flow, and creatinkinase activity in the effluent. Data are expressed as mean +/- SEM. Significant differences were defined as probabilities for each test of p less than 0.05. Four hours of complete warm ischemia resulted in a severe reduction of adenosine triphosphate (4.0 +/- 0.8 vs 27.1 +/- 6.7 mumol/gm protein, p less than 0.001) and no contractions could be stimulated (0.0 +/- 0.0% CC). Muscle pH fell to 6.3 +/- 0.1 (p less than 0.001), and ultrastructural damage occurred (score 3.3 +/- 0.4 vs 0.8 +/- 0.1, p less than 0.002). However, there was only a slight increase in water content of the soleus muscle (78.7 +/- 0.2% vs 74.8 +/- 1.1%, p less than 0.05) without increase in limb volume (103.6 +/- 0.6% CV). In addition mitochondrial function was preserved well: mitochondrial oxidative phosphorylation capacity remained at 94% of control levels, ST3 at 93%, and ADP/O at 100% of control. Most importantly, controlled reperfusion restored immediate contractility in all limbs and was superior in all parameters investigated compared to uncontrolled reperfusion. These data support our inference that necrosis of skeletal muscle does not invariably occur after four hours of complete warm ischemia and suggest that muscle salvage by controlled reperfusion is possible after at least 4 hours of warm ischemia. PMID- 1939332 TI - Perioperative arterial monitoring in patients with severe occlusive disease. AB - Special problems exist in the study and intraoperative monitoring of patients with severe occlusive vascular disease involving all extremities and with symptomatic brachiocephalic or coronary artery disease. We report 3 such patients who underwent arteriography via a percutaneous translumbar aortic catheter. All patients then underwent successful arterial reconstructive procedures utilizing the same translumbar catheter for arterial pressure monitoring and blood gas analysis. Percutaneous translumbar aortic catheters provide both a safe method for studying patients with four extremity occlusive vascular disease and reliable arterial access to monitor these patients intraoperatively. PMID- 1939333 TI - Outcome of intraarterial urokinase for acute vascular occlusion. AB - Intraarterial urokinase (IAUK) was administered to 33 patients on 40 occasions for the treatment of acute extremity ischemia and long-term patency was assessed. Lysis was successful in 39 of the 40 cases (95%). Occlusive thrombus was cleared in 12 of 13 patients with native artery occlusion (7 complete, 5 partial), 8 of 9 with autologous vein grafts (5 complete, 3 partial), and in all 18 patients with synthetic grafts (17 complete, 1 partial). The primary cumulative patency following successful IAUK was 100% for native arteries and 47% for synthetic grafts at 12 months, and 23% for autologous grafts at 9 months. The difference in rethrombosis rate between autologous vein (67%) and native artery (0%) was significant (p = 0.02) as was the difference between infrainguinal prosthetic grafts (63%) and native artery (p = 0.025). IAUK is most effective for the treatment of native artery occlusion, but is significantly less effective for thrombosed infrainguinal autologous vein or synthetic grafts due to the likelihood of reocclusion, despite the high immediate success rate. For autologous vein grafts, lysis is frequently incomplete and patency rapidly deteriorates regardless of adjunctive therapy to relieve the underlying obstruction. PMID- 1939334 TI - The Vena Tech filter: evaluation of a new inferior vena cava interruption device. AB - Expanded indications for caval interruption and earlier diagnosis of deep venous thrombosis have resulted in increased use of transvenous caval interruption devices and have intensified the search for the ideal caval filter. The Vena Tech vena cava filter is a percutaneous, transvenous caval interruption device which was recently introduced in the United States. We reviewed our experience with this filter. During the period of September 1989 to July 1990, 41 patients underwent placement of the Vena Tech filter. Indications for filter insertion included deep venous thrombosis with a contraindication to anticogulation (61%), pulmonary embolism while on anticoagulant therapy (29%), and prophylaxis (10%). Insertion was accomplished percutaneously in 40 patients (98%) and via cutdown in one patient. Thirty-nine (95%) were placed from the right internal jugular vein and two (5%) from the right femoral vein. There were no deaths related to filter placement. Incomplete opening of the filter occurred in 8 patients (19%); however, the incidence of deployment problems decreased as our experience increased. Pulmonary embolism after filter placement occurred in one patient (2%). Duplex scan was obtained postoperatively in 15 patients (mean follow-up 120 days). The inferior vena cava was patent in all patients, although nonoccluding thrombus was identified in the filter in one patient. We conclude the Vena Tech filter is an effective device for caval interruption, is easily inserted, and is associated with minimal morbidity. PMID- 1939335 TI - Popliteal artery entrapment syndrome. Report of two cases. AB - We treated two patients with popliteal artery entrapment syndrome. In one, the popliteal artery was entrapped and obstructed in its abnormal course around the medial head of the gastrocnemius muscle, which was inserted into the femur laterally and cephalad (type II in Delaney's classification). In the other patient, the popliteal artery followed a normal course but was compressed laterally by the medial head of the gastrocnemius muscle, which was aberrantly inserted into the femur considerably higher and more lateral than usual, and was occluded. This could not be fitted into Delaney's or Insua's classification. Arterial reconstruction was successful with an autovein graft in the former case and an in situ bypass graft in the latter. We suggest a modification of type IV in Delaney's classification, so that when the popliteal artery is compressed by an aberrant muscular or tendinous structure in the popliteal fossa it can be included. PMID- 1939336 TI - Adventitial cystic disease of the popliteal artery: early recurrence after CT guided percutaneous aspiration. AB - Adventitial cystic disease of the popliteal artery is a rare condition of debated aetiology. The recommended treatment has been cyst removal with or without replacement of the artery. Recently percutaneous aspiration has been suggested as another method of treatment for this condition. In this case, percutaneous aspiration was performed twice. Surgical intervention was eventually performed because of early cyst recurrence. Our experience suggests that aspiration is a treatment option but, if used, close long-term follow-up is necessary to detect recurrence. PMID- 1939337 TI - Atheroembolism presenting as selective muscle embolisation. AB - Two cases of occult aneurysmal disease presenting with select muscle embolisation are described. Both cases were characterised by symptomatology suggestive of occlusive disease but in the presence of normal pulses. It is concluded that the clinical features allow early diagnosis of this uncommon presentation of aneurysmal disease. PMID- 1939338 TI - Biologic fate of cryopreserved human saphenous allografts: case report and hypothesis. AB - A femoroperoneal bypass using a cryopreserved human saphenous allograft was performed on a patient who presented with critical ischemia of the left lower extremity. The patient died of myocardial infarction 48 hours later and the graft was examined histologically. There was karryorhexis and focal neutrophilic infiltrate in the media underlying a layer of fibrin on the intimal surface. Immunoperoxidase studies showed nonspecific luminal deposition of immunoglobulins and fibrinogen. The histologic changes that occur in cryopreserved venous allografts are similar in experimental and human material and may be the result of anoxia of the vessel wall rather than immunologic mechanisms. PMID- 1939339 TI - Human keratinocyte growth-promoting activity on the surface of fibroblasts. AB - To proliferate in serum-containing medium, normal human keratinocytes must be co cultured with fibroblast feeder cells. Conditioned medium from feeder cell cultures cannot substitute for the cells themselves. We tested the hypothesis that fibroblasts display a keratinocyte growth-promoting activity on their outer cell surface. The results of our investigation showed that (1) glutaraldehyde fixed fibroblast feeder cells promote keratinocyte growth, (2) the growth promoting effect requires contact between fixed fibroblasts and keratinocytes, and (3) feeder activity is highly enriched within the plasma membrane fraction of fibroblasts. We conclude that at least part of the fibroblast "feeder" activity involves a keratinocyte growth-promoting factor which is bound to the outer surface of fibroblast plasma membranes. PMID- 1939340 TI - Interleukin-6 and transforming growth factor-beta synergistically stimulate chondrosarcoma cell proliferation. AB - This study examines the regulation of Swarm rat chondrosarcoma (SRC) cell proliferation in vitro. In serum-free cultures, SRC cells showed only transient DNA synthesis and this was increased by serum. Transforming growth factor-beta (TGF-beta) was identified as an essential serum component, since the mitogenic effect of sera was related to their TGF-beta content and neutralized by antibody to TGF-beta. Among a large panel of agents tested, TGF-beta was the only factor that stimulated proliferation in serum-free media. The TGF-beta isoforms TGF-beta 1 and TGF-beta 2 induced similar dose-dependent increases with maximal 62.5-fold stimulation at 10 ng/ml. Interleukin-6 (IL-6) was identified as a new factor that stimulated SRC proliferation. IL-6 effects were serum-dependent and their magnitude correlated with the TGF-beta content in different serum preparations. In serum-free cultures where IL-6 by itself had no detectable effect it caused up to 7.6-fold increased proliferation in the presence of small doses of TGF-beta (0.01-0.1 ng/ml). This synergy was unique, since no other factor tested synergized with IL-6 or TGF-beta. In examining potential mechanisms for this synergy it was found that TGF-beta increased IL-6 receptor expression. In summary, these results identify IL-6 as a new and TGF-beta as the most potent growth factor for chondrosarcoma cells and describe novel interactions between these factors in the regulation of cell growth. PMID- 1939341 TI - Inhibition of phorbol ester-induced monocytic differentiation by dexamethasone is associated with down-regulation of c-fos and c-jun (AP-1). AB - Previous studies have shown that treatment of human myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of monocytic differentiation and expression of the c-jun and c-fos early response genes. The present work demonstrates that the glucocorticoid dexamethasone inhibits TPA-induced increases in c-jun and c-fos mRNA levels in U-937 leukemia cells. These findings were associated with a block in appearance of the monocytic phenotype, including inhibition of TPA-induced increases in lamin A, lamin C, and vimentin transcripts. Other studies have demonstrated that TPA-induced monocytic differentiation and expression of the c-jun and c-fos genes in myeloid leukemia cells are regulated by protein kinase C (PKC). The finding that dexamethasone has no effect on TPA-induced activation of PKC suggests that this glucocorticoid inhibits signals downstream or parallel to this enzyme. Nuclear run-on assays demonstrate that: (1) induction of c-jun and c-fos expression by TPA is regulated by transcriptional mechanisms, (2) TPA-induced expression of c-jun and c-fos does not require protein synthesis, and (3) TPA-induced expression of both genes is inhibited at the transcriptional level by dexamethasone. To further define the effects of dexamethasone at the molecular level, we prepared a series of deleted c-jun promoter fragments linked to the chloramphenicol acetyltransferase (CAT) gene. Increases in CAT activity during transient expression of these constructs in TPA-treated U-937 cells could be assigned to the region (-97 to -20) of the promoter that contains the AP-1 binding site. This induction of CAT activity was sensitive to dexamethasone. These findings suggest that dexamethasone down regulates TPA-induced transcription of the c-jun gene during monocytic differentiation by inhibiting activation of the AP-1 site. PMID- 1939342 TI - Recycling kinetics and transcytosis of transferrin in primary cultures of bovine brain microvessel endothelial cells. AB - Primary cultures of bovine brain microvessel endothelial cells (BMECs) were used to examine the cycling kinetics of ferrotransferrin (Tf) and to provide evidence for a transcytotic pathway in vitro. Binding of 125I-Tf to BMECs grown on matrix coated plastic was measured in the presence of saponin to calculate the total number of transferrin receptors (TfRs). Nonlinear regression analysis of the binding isotherm showed that there were 100,000 high-affinity receptors per cell and that expression was maximum at cell confluence. Binding of Tf at 4 degrees C indicated that there was a large intracellular receptor pool comprising 85-90% of the total cellular receptors. Accumulation of Tf at 37 degrees C, inhibited at low temperature and in the presence of metabolic poisons, occurred with an initial rate coefficient of 0.030 min-1 and this decreased by 83% after 60 min. Concomitant accumulation of 59Fe from Tf-59Fe was linear. In the absence of externally added ligand, 80% of the accumulated 125I-Tf was released into the medium with a rate coefficient of 0.017 min-1 and this was inhibited at low temperature. In the presence of the weak base primaquine, the accumulation of Tf and 59Fe and the efflux of Tf were decreased. Moreover, phorbol myristate acetate (PMA) caused a 30% increase in surface TfRs and an 82% increase in Tf accumulation, although the size of the recycling pool remained unchanged. Despite the low numbers of TfR expressed by post-confluent cells, filter-grown BMEC monolayers were used to measure transcytosis of Tf. A small portion of the Tf that was accumulated from the apical side entered a transcytotic pathway. Most of the Tf and all of an accumulated fluid-phase tracer were recycled towards the apical side. These results showed that cultured BMECs cycle Tf-TfR complexes slowly and vectorially and suggested that the large intracellular receptor pool may facilitate steady state accumulation and regulate transcellular transport of iron. PMID- 1939343 TI - Enhanced sulfated-proteoglycan core protein synthesis by incubation of rabbit chondrocytes with recombinant transforming growth factor-beta 1. AB - Rabbit articular chondrocytes were incubated with recombinant transforming-growth factor-beta 1 (rhTGF-beta 1) and its effect on newly synthesized proteoglycan measured. rhTGF-beta 1 stimulated proteoglycan synthesis at a concentration as low as 5 ng/ml without further increases in radiosulfate incorporation up to 50 ng/ml. The quantitative increase in radiosulfate incorporation in rh-TGF-beta 1 treated chondrocytes was greater in the cell-associated culture compartment than in the medium compartment. rhTGF-beta 1 promoted an increased proteoglycan retention in the cell-associated compartment as evidenced by an increase in the t1/2 of retention from 8 h to 11 h. Specific enhanced synthesis of [35S] methionine-labeled core proteins was seen in rh-TGF-beta 1-treated chondrocytes. rh-TGF-beta 1 increased the synthesis of the 2 core proteins derived from hydrodynamically large proteoglycans. They possessed apparent molecular weights of greater than 480 kD and 390 kD after 3-5% acrylamide gel electrophoresis. A compartmental analysis revealed that the cell-associated culture compartment contained only the larger of the 2 core proteins derived from large proteoglycans. Two other core proteins with apparent molecular weights 52 kD and 46 kD were also stimulated by rhTGF-beta 1. These results indicated that TGF-beta probably plays a significant role in stimulating proteoglycan core protein synthesis in articular chondrocytes and therefore may be an important growth factor in the restoration of cartilage extracellular matrix after injury. PMID- 1939344 TI - Regulation of expression and intracellular distribution of calreticulin, a major calcium binding protein of nonmuscle cells. AB - In the present study we have demonstrated the presence of calreticulin, a major Ca(2+)-sequestering protein of nonmuscle cells, in a variety of cell types in tissue culture. The protein localizes to the endoplasmic reticulum in most cell types and also to the nuclear envelope or nucleoli-like structures in some cell types. Calreticulin is enriched in the rough endoplasmic reticulum, suggesting a possible involvement in protein synthesis. Calreticulin terminates with the KDEL COOH sequence, which is likely responsible for its endoplasmic reticulum localization. Unlike some other KDEL proteins, calreticulin expression is neither heat-shock nor Ca(2+)-shock dependent. Using a variety of metabolic inhibitors, we have shown that the pool of calreticulin in L6 cells has a relatively slow turnover and a stable intracellular distribution. In proliferating muscle cells in culture (both L6 and human skeletal muscle) calreticulin is present in the endoplasmic reticulum, and additional intranuclear staining is observed. When fusion of the L6 cells is inhibited with either a high serum concentration or TGF beta or TPA, the nucleolar staining by anticalreticulin antibodies is diminished, although the presence of calreticulin in the endoplasmic reticulum remains unchanged. In contrast, in differentiated (i.e., fused) muscle cells neither intranuclear nor intracellular staining for calreticulin is present. We conclude, therefore, that calreticulin is abundant in the endoplasmic reticulum in proliferating myoblasts, while it is present in only small amounts in sarcoplasmic reticulum membranes in terminally differentiated myotubes. We propose a model for the domain structure of calreticulin that may explain the differential subcellular distribution of this protein. Because of its widespread distribution in nonmuscle tissues, we postulate that calreticulin is a multifunctional protein that plays an important role in Ca(2+) sequestering and thus that it is the nonmuscle analog of calsequestrin. PMID- 1939345 TI - Caco-2 cells cultured in serum-free medium as a model for the study of enterocytic differentiation in vitro. AB - Caco-2 cells, which express spontaneous enterocytic differentiation at confluency, is one of the most relevant in vitro models for the study of differentiation and regulation of intestinal functions. However, these cells are normally cultured in the presence of 15-20% serum which renders extremely complex the identification of the factors involved in the regulation of both proliferation and differentiation. This study has been devoted to the establishment of chemically defined culture conditions which can sustain growth and differentiation of Caco-2 cells. The replacement of serum by ITS (insulin, transferrin, and selenium) allowed for normal structural and functional differentiation of cells as revealed by the establishment of cell polarity and the expression of brush-border membrane enzyme markers (sucrase, maltase, lactase, alkaline phosphatase, gamma-glutamyltransferase, aminopeptidase N, and dipeptidyl-dipeptidase IV), although the levels of sucrase activity were lower in ITS-supplemented medium. Coating petridishes with either type IV collagen or basement membrane proteins (Matrigel) did not improve the differentiation of cells, brush-border membrane enzyme activities being, in fact, lower when the cells were grown on these substrata. When triiodothyronine (T3, 5 x 10(-8) M) was added to the ITS-supplemented medium, disaccharidase and alkaline phosphatase activities were significantly increased while gamma-glutamyltransferase activity was diminished by T3 and stimulated by epidermal growth factor (1.6 x 10(-6) M). On the other hand, hydrocortisone (HC, 10(-6) M) did not modify disaccharidase and peptidase activities. These data clearly show that Caco-2 cells can be maintained in serum-free medium and that this system allows the study of the factors involved in the regulation of the differentiation of enterocyte in vitro. PMID- 1939346 TI - Responsiveness of the increase in C-fos mRNA levels depends on the inducer and the cell's past. AB - In this paper we show that in C3H10T1/2 mouse fibroblasts, the inducibility of c fos mRNA by heat shock or serum addition is strongly dependent on the cell's past. Four hours after a heat shock, a time point where the induced c-fos mRNA has disappeared, c-fos mRNA could not be induced again by a second heat shock. Four hours after serum addition, by which c-fos was induced, a second serum addition also failed to induce c-fos mRNA again. When, however, serum was added 4 hours after heat shock or heat shock was given 4 hours after serum addition, levels of c-fos mRNA could be enhanced again. The induction by serum of c-fos mRNA levels in thermotolerant cells might be related to their increased stimulation of DNA synthesis as compared to control cells. PMID- 1939347 TI - Isolation of variants of Chinese hamster ovary cells with abnormally low levels of GSH: decreased ability to cleave endocytosed disulfide bonds. AB - Mutants of Chinese hamster ovary cells were selected for resistance to a 3 hour exposure to 4 microgram/ml N-methyl-N'-nitro-N-nitrosoguanidine and tested for glutathione (GSH) levels. Six of eight clones that survived the initial treatment had reduced GSH levels ranging from 26 to 61% of wild-type values. These eight cell lines were tested for their susceptibility to a drug conjugate in which methotrexate (MTX) is disulfide-linked to poly(D-lysine) (MTX-SS-PDL) to test their capacity to cleave the endocytosed disulfide bond and release free MTX from this otherwise undegradable drug conjugate. We had shown that wild-type cells were killed by approximately 1 x 10(-7) M MTX given as free drug, as MTX-poly(L lysine) or as MTX-SS-PDL, but were not affected by MTX-poly(D-lysine). All six lines with abnormally low levels of GSH were resistant to MTX-SS-PDL. The variants with the lowest levels of GSH (MNR-5 and MNR-10) were tested further and showed near-normal sensitivity to MTX and MTX poly(L-lysine). As expected, both lines were hypersensitive to melphalan. They were, however, normally sensitive to diphtheria toxin and ricin, indicating that some cleavage of the interchain disulfides in these protein toxins occurs even when cellular GSH is abnormally low. The lesser GSH requirement for toxin activation may be due to their extraordinary potency. PMID- 1939348 TI - Differences in preferential synthesis and redistribution of HSP70 and HSP28 families by heat or sodium arsenite in Chinese hamster ovary cells. AB - Since both heat and sodium arsenite induce thermotolerance, we investigated the differences in synthesis and redistribution of stress proteins induced by these agents in Chinese hamster ovary cells. Five major heat shock proteins (HSPs; Mr 110, 87, 70, 28, and 8.5 kDa) were preferentially synthesized after heat for 10 min at 45.5 degrees C, whereas four major HSPs (Mr 110, 87, 70, and 28 kDa) and one stress protein (33.3 kDa) were preferentially synthesized after treatment with 100 microM sodium arsenite (ARS) for 1 hr. Two HSP families (HSP70a,b,c, and HSP28a,b,c) preferentially relocalized in the nucleus after heat shock. In contrast, only HSP70b redistributed into the nucleus after ARS treatment. Furthermore, the kinetics of synthesis of each member of HSP70 and HSP28 families and their redistribution were different after these treatments. The maximum rates of synthesis of HSP70 and HSP28 families, except HSP28c, were 6-9 hr after heat shock, whereas those of HSP70b and HSP28b,c were 0-2 hr after ARS treatment. In addition, the maximum rates of redistribution of HSP70 and HSP28 families occurred 3-6 hr after heat shock, whereas that of HSP70b occurred immediately after ARS treatment. The degree of redistribution of HSP70b after ARS treatment was significantly less than that after heat treatment. These results suggest that heat treatment but not sodium arsenite treatment stimulates the entry of HSP70 and HSP28 families into the nucleus. PMID- 1939349 TI - The level of substrate ornithine can alter polyamine-dependent DNA synthesis following phorbolester stimulation of cultured hepatoma cells. AB - Although the precise intracellular function(s) of the polyamines remain incompletely defined, a myraid of evidence now shows that the polyamines must accumulate or be maintained at a specific intracellular concentration in order for all mammalian cells to grow or divide. The initial step in polyamine biosynthesis normally involves the decarboxylation of ornithine by the enzyme ornithine decarboxylase (ODCase E.C. 4.1.1.17) to yield putrescine. Increases in the steady-state level of intracellular ornithine have been reported to markedly alter the accumulation of the polyamines following stimulation of Reuber H35 Hepatoma cells with 12-O-tetradecanoylphorbol-beta-acetate (TPA) in the presence of serum (Wu and Byus: (Biochem. Biophys. Acta 804:89-99, 1984); Wu et al.: (Cancer Res. 41:3384-3391, 1981). We wished to determine whether or not incubation of H35 hepatoma cells with exogenous ornithine would result in a stimulation of DNA synthesis following treatment with the mitogens TPA and insulin. For these studies, H35 cells were maintained under serum-free conditions for 2-3 days in order to obtain synchronous cultures suitable for analysis of the level of DNA synthesis. Cultures treated in this manner were highly viable, maintained similar growth rates, and possessed the equivalent levels of intracellular ornithine and polyamines as the serum-containing cultures. Arginine levels, however, were approximately twofold higher following culture under serum restricted conditions for 3 days. The addition of exogenous ornithine (0.5 mM) was accompanied by a 4-5-fold increase in intracellular steady-state ornithine levels and by a 6-8-fold increase in the presence of TPA and ornithine. In a manner identical to the serum-containing cultures (Wu and Byus (1984] the addition of TPA and exogenous ornithine to the serum-free cells caused a dose dependent increase in intracellular putrescine (up to 5-fold) and a concomitant decrease in ODC activity in comparison to stimulation with TPA alone. The addition of TPA led to a 3-5-fold increase in the incorporation of tritiated thymidine into DNA. In the presence of exogenous ornithine, TPA-induced DNA synthesis was further stimulated more than twofold in a dose-dependent manner. Insulin (10(-10)-10(-8) M) proved to be more efficacious as a mitogen in the H35 cells and led to greater stimulation of DNA synthesis than TPA. Insulin alone also resulted in a higher steady-state level of ornithine and putrescine in comparison with TPA alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939350 TI - An update on wound management. AB - This article provides an update on wound management with wound diagnosis and treatment discussed in terms of the normal cellular events of the wound healing process. The role of growth factors as cell regulators, the importance of wound fluids to wound metabolism, and the deleterious effects of some wound cleansers, disinfectants, and modalities are reviewed. Treatment guidelines are suggested based on negative or positive cellular response to individual management techniques. Wound evaluation, diagnosis, and treatment are considered in terms of a new color concept that simplifies clinical decision making. An explanation of the relatively new microenvironmental dressings designed to maintain wound humidity and speed wound healing is provided. A more physiologic approach to managing the simple and complex wound may prove to speed the process of epithelialization, contraction, and collagen deposition while diminishing the problems associated with delayed or inadequate healing. The wound healing process is subject to manipulation and facilitation by the clinician, a concept that is certain to receive much attention in the next decade. The importance of a scientific approach to this aspect of our discipline cannot be overemphasized. PMID- 1939351 TI - Frontiers in hand rehabilitation. PMID- 1939353 TI - Review and comparison of current trends in the postoperative management of tendon repair. AB - The precision of the Evans/Burkhalter protocol and the work by Silverman and associates exemplify one of the most valuable of all current trends in rehabilitation of the healing tendon. Knowledge of tendon excursion at each level and throughout the range of motion in each joint gives us safe parameters for tendon mobilization. Hand rehabilitation is becoming more of a science while remaining an art. Research into tendon healing, nutrition, anatomy, biomechanics, and physiology gives us a solid basis for our treatment techniques. We now need to replicate studies already performed and quantify more precisely the data we have. Many questions remain unanswered. There is a wide variety in the position of splinting for flexor tendon mobilization under current protocols: What joint positions are optimal and why? The number and frequency of repetitions in early mobilization protocols varies greatly: What number and frequency is more appropriate for which patients? How much tendon excursion will control adhesions, promote healing, and avoid gap formation or elongation of the repair? How much force should we apply passively to maintain or increase joint motion? How soon should we start active motion, and how can we control the strength of those early muscle contractions? Do "place-hold" exercises truly place less tension on the repair site? How soon should we begin resisted exercise, and how much resistance are we applying with each type of exercise? Should blocking exercises be considered resistive? How should tendon management protocols be adapted in the presence of associated injuries? Lack of space has prevented discussion here of recent and needed research in a number of areas, such as the effectiveness and appropriate precautions for the use of ultrasound, iontophoresis, and neuromuscular electrical stimulation in tendon management. The evidence is growing, but we have a long way to go. To improve our clinical results, the trend toward precision must continue and grow. PMID- 1939352 TI - AIDS in the hand patient: the team approach. AB - Hand surgeons and therapists were faced with a new clinical entity in the 1980s with the emergence of hand and upper extremity infections in patients with AIDS and HIV disease. This entity has become a worldwide epidemic of vast proportions and has proven to be one of the major health concerns of the 1990s. It seems likely that treatment of patients with this devastating disease for hand infections or more routine upper extremity problems will become routine in the future. The reality of surgical treatment and hands-on rehabilitative therapy for patients with a life-threatening infectious disease has been a concern voiced publicly by very few health care professionals, yet discussed quietly among colleagues quite frequently. Our aim must be to provide the highest quality of health care to this group of hand patients, just as we do for all other patients, while at the same time providing the safest possible environment for all members of the health care team. It appears that there is a higher incidence of HIV infection among hand patients than is noted in the general public; therefore, the hand surgeon and medical team should pay particular attention to the rapidly advancing front of new information available regarding care for this challenging group of patients. Hand surgeons and therapists are entering the 1990s armed with a wealth of new and valuable information about HIV disease that has been produced by intensive basic science research and clinical observations accumulated over the last 10 years. The fears generated by the initial misinformation and lack of information concerning modes of transmission of HIV have generally been supplanted by a more rational approach to patient care, fostered by the more accurate scientific information currently becoming available. Unfortunately, the rational approach to the HIV-related political and socioeconomic issues has not yet overtaken the discrimination and stereotyping of the populace stricken with HIV disease. It remains the responsibility of the medical community to continue research efforts aimed at delineating the clinical deficiencies manifested by these patients and determining their effects on treatment regimens for both the unique and commonplace medical and orthopedic problems noted in this patient population. PMID- 1939354 TI - Microsurgery: directions for the 1990s. AB - Speculating on the possible advances of microsurgery in the 1990s has encompassed discussion of transplantation technique, biochemistry, monitoring, and nerve and motor reconstruction. This article, however, is by no means exhaustive, and many other discoveries and innovations may come from areas not discussed here. The only clearly incorrect possibility concerning microsurgery in the 1990s is that nothing exciting will happen. PMID- 1939355 TI - Physiology of nerve repair: a research update. AB - Understanding the anatomy and response to injury of the peripheral nerve is important for the surgeon treating peripheral nerve injuries. Appropriate treatment also requires proper classification of the injury. Although great advances have been made in the area of microsurgical repair, results remain unpredictable. Future work in the areas of immunology, nerve conduits, and growth factors will, it is hoped, provide further information to allow for better functional recovery. PMID- 1939357 TI - Stress testing in nerve compression. AB - Peripheral nerve compression syndromes most often produce neuropathic changes that are recordable by conventional electrophysiologic testing techniques. Occasionally, a patient exhibits all the appropriate clinical signs, symptoms, and history of a compartment syndrome, such as a carpal tunnel syndrome, but electrophysiologic testing procedures will be normal, thus seeming to identify no neuropathic component to the syndrome. Researchers have reasonably concluded that wrist position or hand activity can have an adverse affect on intracompartmental carpal pressures, with resultant ischemic changes in epineural blood supply and subsequent compromise in nerve conduction parameters during and for a short time after the ischemic event. The stress testing protocol presented here identifies such changes, which would otherwise go undetected or undocumented and which may lead to unsuccessful clinical decisions regarding management. Sample tracings of actual cases are presented to demonstrate actual changes produced by the use of the protocol. This test protocol is used only when conventional testing is normal in the presence of appropriate clinical symptomatology. PMID- 1939356 TI - Therapeutic techniques to enhance nerve gliding in thoracic outlet syndrome and carpal tunnel syndrome. AB - By studying capabilities inherent in the nerve proper and carefully considering patient complaints and limitations, the surgeon-therapist team may be able to guide patients through a restorative phase via nerve gliding techniques. Nerve symptoms must be heeded when employing rehabilitation techniques. Rather than encouraging the patient to push beyond nerve pain either proximally or distally, the patient is instructed to perform exercises in positions that enhance nerve gliding in a slow, controlled manner. "Tincture of time" is prescribed as the patient advances to a less symptomatic level of function. PMID- 1939358 TI - Advances in sensibility evaluation. AB - What is needed is a quick, practical, cost-effective measurement instrument that can be depended upon to provide clear and reliable information regarding normal versus abnormal function. In the future, objective measurements will enable review of patient peripheral nerve injuries and neuropathies in treatment populations and will allow direct correlation of peripheral nerve status with treatment. Important points can be summarized as follows: (1) With newer technology, improved testing instruments are possible that can both expand understanding of clinical conditions and in the end simplify testing through stimulus control with errors eliminated. (2) With understanding of the requirements for controlled stimuli, clinicians can assess the objectivity of any current and future test instrument and/or can use an instrument in as repeatable a method as possible within its identified limitations. (3) Many current test instruments have been helpful in providing useful clinical information, but better instrument control is needed to improve the quality of information and to develop minimum recommendations for testing. (4) Newer instruments that have undergone instrument reliability testing should be compared with existing instruments that have met the requirements for reliability in a valid protocol before they can be said to have greater or less value in detecting clinical status. (5) Data regarding reliability studies should be available and should not be taken at face value alone; just because a manufacturer states reliability studies have been done, or a paper concludes an instrument is reliable, does not mean the instrument or testing protocol meets the requirements for scientific design. (6) A test instrument needs to be as sensitive as the system it is trying to measure; most currently available instruments apply stimuli too gross to sensitively detect abnormal function, or to sensitively detect early changes (improvement or worsening) in clinical status. (7) For the first time there exists the possibility of computer-controlled instruments for evaluating long standing physiologic concepts, and there will soon be an explosion of newer information under which all instruments should be considered. (8) The Semmes Weinstein monofilaments are one of the most objective instruments (if not the most) and are available for clinical testing either for detailed mapping or for screening extent and degree of nerve pathology; combination with electroneuromyography is recommended in determining level of involvement. PMID- 1939359 TI - Update in splinting materials and methods. AB - Current hand splinting methods, materials, and components are reviewed and summarized. Additional subjective and objective tests of thermoplastic materials are performed and results combined with those from other studies. Available samples of thermoplastic materials are tested for fatigue and viscoelastic properties using standard compression cycling methods. Soft splint materials are seeing increased application and appear to be the material for the future. PMID- 1939360 TI - Cumulative trauma disorder of the upper limb. AB - The current status of cumulative trauma disorder of the upper limb is examined from the standpoint of its long history, its current controversies, and the philosophic basis of the present laws, which control management of the condition. The future needs that should permit cumulative trauma disorders to be better understood, better managed, and better legislated are also addressed. PMID- 1939361 TI - Work hardening: a mandate for hand therapy. AB - Conditioning for return to work has become an integral part of the comprehensive hand rehabilitation program. Through experience and the development of guidelines, the practice of work hardening has matured. Skillful evaluation of the injured worker has enhanced the efficacy of work hardening programs. An understanding of program planning, implementation, and influential economic factors assist the work hardening team in creating and maintaining program excellence. PMID- 1939362 TI - Immunobiochemical evidence for the loss of sperm specific histones during male pronucleus formation in monospermic zygotes of sea urchins. AB - To obtain information on the remodeling of sperm chromatin during male pronuclei formation, we have followed the sperm specific histones (SpH) that form the nucleosomal core by Western immunoblot analysis with polyclonal antibodies directed against the core SpH. The results obtained indicate that the complete set of SpH is absent from zygote chromatin at the beginning of the first S phase. The disappearance of SpH is not coincidental for the five histone classes: SpH4 and SpH3 are lost 5-15 min post insemination (p.i.), SpH2B and SpH2A disappear 20 40 min p.i., and SpH1 is progressively diminished up to 30 min p.i. This order of sperm chromatin remodeling is not affected by the inhibition of protein synthesis by emetine, indicating that the factor(s) responsible for SpH disappearance are present in unfertilized eggs. The lost SpH's are not replaced by newly synthesized CS variants, since the basic proteins synthesized de novo during male pronuclei formation are not incorporated into chromatin remaining in the cytoplasm. These newly synthesized proteins are different from the CS variants as judged by their electrophoretic migration. PMID- 1939363 TI - Probing nucleosome core secondary structure before and after alpha-chymotrypsin treatment by Raman spectroscopy and thermal denaturation. AB - Nucleosome cores were digested with alpha-chymotrypsin until histone H3 was degraded to a partial histone, CP1. As we reported previously, cleavage occurred at leucine 20 to H3 and resulted in an increase in circular dichroism between 265 to 285 nm. Some modest core unfolding was also observed as determined by a small decrease in the sedimentation coefficient. Studies reported here deal with the analysis of core secondary structure and subsequent perturbation caused by treatment with alpha-chymotrypsin. Raman spectroscopy indicated that chymotryptic treatment promoted a change in the conformational environment of a population of core histone tyrosines. In addition, a shift from B-form to an intermediate B- or A-form was observed for core DNA. High-resolution thermal denaturation was used to determine alterations in the stabilization of core DNA related to perturbation of the core histones. Brief chymotryptic treatment indicated changes in both pre melt and irreversible transitions. PMID- 1939364 TI - Glucocorticoid regulation of rat liver urate oxidase. AB - Urate oxidase, an enzyme involved in purine catabolism, comprises the crystalline core of rat liver peroxisomes. An affinity-purified monospecific antibody was developed to study the expression of urate oxidase protein levels. Immunoreactive urate oxidase was not detectable in prenatal liver; however, it is present at low levels after birth until approximately day 15 (postnatal age); expression sharply increases just prior to day 20, after which the enzyme is maintained at adult levels. This pattern of expression was similar to that of another peroxisomal enzyme, catalase; these developmental increases reflect the increase in peroxisomal number. Administration of exogenous glucocorticoid hormone to 10-day old rats resulted in a precocious rise (2.5-fold) in urate oxidase levels. Adrenalectomy at 10 days of age did not cause decreased levels in the fourth week of life. In adult animals, while exogenous glucocorticoid administration did not influence urate oxidase levels, adrenalectomy at 60 days of age decreased urate oxidase levels to 40 percent of control levels. Subsequent administration of exogenous glucocorticoid hormone restored urate oxidase to normal levels. Parallel studies of catalase levels indicate that this glucocorticoid-sensitive response is not generalized for all peroxisomal proteins. Our results suggest that peroxisomes proliferate during early postnatal development, but after this process is complete, the biogenesis of individual peroxisomal proteins may be independently regulated. PMID- 1939366 TI - Adenosine deaminase deficiency due to heterozygous abnormality consisting of a deletion of exon 7 and the absence of enzyme mRNA. AB - An adenosine deaminase (ADA;EC 3.5.4.4)-deficient B lymphoblastoid cell line BADO5 derived from a Japanese patient with severe combined immunodeficiency disease and two B lymphoblastoid cell lines, BAMO5 from his mother and BAFO5 from his father, were characterized. To identify mutations affecting ADA activity, we prepared cDNAs to ADA mRNAs of the BADO5 cell line for nucleotide sequencing. Sequence analysis of one of the BADO5 ADA cDNA clones revealed deletion of exon 7, and one point mutation of base 629 from G to A that did not affect the amino acid sequence. All clones of the BADO5 cell line so far examined showed the absence of exon 7 by Southern blotting analysis. Ribonuclease protection assay with an RNA probe spanning from exon 5 to exon 11 showed that the BADO5 ADA mRNA had a deletion of exon 7, the BAMO5 mRNA had normal length, and the BAFO5 mRNA had two species with a deletion of exon 7 and with normal length. Consequently, the patient's ADA genes resulted from one allele of the BAMO5 ADA gene that did not produce a detectable mRNA, and the other allele of the BAFO5 ADA gene producing an aberrant mRNA without exon 7. PMID- 1939365 TI - Co-regulation of heme oxygenase and erythropoietin genes. AB - The mechanism responsible for the accumulation of heme oxygenase and erythropoietin (epo) transcripts due to cobalt chloride (CoCl2) administration was investigated in rat kidney using a rat heme oxygenase and mouse epo probes. We found an increase of heme oxygenase transcripts in kidney in response to CoCl2. Quantitative evaluation of the heme oxygenase mRNA changes, by scanning densitometry, indicated that the levels of mRNA encoding heme oxygenase were increased by about fiftyfold in rat kidney after administration of CoCl2. That the increase in heme oxygenase mRNA levels resulted from enhanced transcription of the heme oxygenase gene was confirmed by nuclear runoff using isolated rat kidney nuclei after CoCl2 administration. Transcription of the heme oxygenase gene is greatly increased in rat kidney within 1 hr of administration of CoCl2 as evidenced from the levels of 32P-UTP incorporation into the specific transcript. Time course studies showed that stimulation of transcription was increased about fortyfold 3 hr after CoCl2 administration. This stimulation is the most rapid transcriptional response to heavy metals yet described. In addition, Northern blot analysis demonstrated that epo mRNA was first detected 4 hr following CoCl2 administration and reached a maximum at 5 hr. On the other hand, PCR analysis indicated that epo mRNA was increased as early as 1 hr following CoCl2 administration. The fact that CoCl2 caused increased transcription of both the epo and heme oxygenase genes suggests that a common mechanism may be involved in the regulation of these two genes by the heavy metal ion. PMID- 1939367 TI - Facile platelet adhesion to collagen requires metabolic energy and actin polymerization and evokes intracellular free calcium mobilization. AB - The attachment of platelets to collagen-coated microtiter plates at 20 degrees C was inhibited strongly by depletion of metabolic energy or by addition of cytochalasins and was slightly inhibited by the intracellular Ca2+ chelator BAPTA. In keeping with their respective potencies as inhibitors of actin polymerization, cytochalasins D and H were the most potent inhibitors of adhesion, while cytochalasin B was the least potent. Energy depletion, cytochalasin D or, to a much lesser extent, BAPTA also inhibited platelet adhesion to collagen in a suspension assay system at 37 degrees C. Collagen induced platelet cytosolic Ca2+ mobilization was inhibited up to 70% by cytochalasin D and abolished by energy depletion or BAPTA. Elevation of intracellular platelet calcium by treatment with ionomycin had little effect on platelet adhesion to collagen. We propose that rapid platelet spreading along collagen fibers is both energy- and actin-dependent and necessary to produce maximal adhesion needed to elicit Ca2+ mobilization required for subsequent responses. PMID- 1939368 TI - The nucleolus today. PMID- 1939369 TI - Differential dissociation of chromatin digests: a novel approach revealing a hierarchy of DNA-protein interactions within chromatin domains. AB - We describe here a novel approach to the dissection of chromatin structure by extracting DNA fragments from digested nuclei irreversibly immobilized (via proteins) on Celite columns. Three successive gradients (NaCl, LiCl-urea, temperature) are used to release three families of DNA fragments: namely, the 'DNA adherence' classes DNA-0, DNA-I and DNA-II, respectively. This 'protein image' DNA chromatography separates DNA fragments in accordance with the tightness of their bonds with proteins in situ. There are at least two DNA skeleton attachment sites differing from each other by their resistance to the dissociating agents used as well as their susceptibility to DNAase I and S1 nuclease treatments, DNA cross-linking and single-stranded breaks. Several lines of evidence show a specific, topological rather than chemical, DNA-protein linkage at the tight attachment site. A hierarchy of chromatin loops demarcated by these attachment sites was determined. The technique described is generally applicable and can be used both to probe DNA-protein interactions and to map specific DNA sequences within the chromatin domain. PMID- 1939370 TI - Telophase disc: a new mammalian mitotic organelle that bisects telophase cells with a possible function in cytokinesis. AB - We have discovered a novel mitosis-specific human autoantigen that arises at the centromeres of prophase chromosomes, but ultimately participates in formation of an organelle that bisects the cell at late anaphase and during telophase. The organelle, discernible as a three-dimensional disc by confocal microscopy, encompasses the entire midzone diameter, and its distribution survives disassembly of interpolar microtubules by cold temperature treatment and detergent lysis of cells. Cytokinetic furrow contraction proceeds normally in dihydrocytochalasin B (DCB)-treated cells, and antigen distribution in the furrow is unaltered. In DCB, the furrow retracts in early interphase, coincident with loss of normal membrane association with the disc, resulting in the formation of binucleate cells. The midzone disc in both drug-treated and normal cells is present at the correct time and position to play a central role in cytokinesis. By immunocytochemistry, the disc appears to contain myosin but not actin. The position of the disc and the possible presence of myosin suggest that cytokinesis may involve the interaction of the disc organelle with actin in the cell cortex to produce cleavage in mammalian cells. PMID- 1939371 TI - Unexpected destruction of chitosomal chitin synthetase by an endogenous protease during sucrose density gradient purification. AB - Because of their intrinsic low buoyant density, chitosomes can be separated from crude cell homogenates (1000 g or 35,000 g supernatants) of Mucor rouxii by isopycnic sedimentation in sucrose density gradients. To accelerate and simplify the isolation of chitosomes, we centrifuged the cell-free extracts at ultrahigh speed (in a fixed-angle rotor at forces up to 311,000 g Rav) and found that the duration of centrifugation was critical. Prolonged centrifugation at ultrahigh speed caused severe distortion of the chitin synthetase profile in the gradient as the peak of chitosomal chitin synthetase nearly disappeared. We traced the problem to a soluble protease(s) that moved into the chitosome band during protracted centrifugation and destroyed the chitin synthetase activity. The interfering protease was a soluble protein with a sedimentation coefficient of 4.6 S and a pH optimum of 7-7.5, and it was sensitive to PMSF (phenylmethylsulfonyl fluoride), indicating that it was a serine protease. Unlike other proteases, it destroyed chitin synthetase but did not activate the chitin synthetase zymogen. The interfering protease could be eliminated either by adding PMSF to the cells immediately after breakage or by removing the upper part of the sucrose gradient midway through the centrifugation of the cell-free extract and then completing the sedimentation with the 'decapitated' gradient. PMID- 1939372 TI - Adhesion of L1210 cells to modified styrene copolymer surfaces in the presence of serum. AB - The static adhesion of living L1210 cells (in serum-containing medium) to the surface of (styrene/methylmethacrylate) copolymers differing in styrene content (from 5% to 50% of styrene units) was investigated. The examination of wettability of the copolymer surfaces showed that the contact angle of water on the hydrophobic surfaces is an increasing linear function of styrene content in the copolymer. Cell adhesion to the unwettable surfaces is low (within 2-4%). A novel method of modification of the styrene copolymer surfaces was used to render these surfaces suitable for cell attachment. The modification consists of sulfonation of the surfaces with sulfur trioxide at the gas/solid interface. The contact angle of sulfonated copolymer surfaces is a decreasing linear function of styrene content in the copolymer. The contact angle decreases due to the increased number of highly hydrophilic sulfonic groups bonded to styrene. By acetylation of the sulfonated surfaces it was shown that cell adhesion to acetylated surfaces is not diminished and is at the same level as cell adhesion to sulfonated copolymer surfaces. Thus, it can be concluded that sulfonation of copolymer surfaces does not form hydroxyl groups. Cell adhesion to substrata of high wettability stabilizes after 30s. The relative number of cells adhering to the sulfonated copolymer surfaces is a decreasing linear function of the contact angle. For the copolymer surfaces containing 50% of styrene units the contact angle decreases sevenfold, due to sulfonation, and the number of adhering cells increases 40-fold. The results obtained show that for cell-substratum adhesive interaction the presence of sulfonic groups at the substratum surface is important. PMID- 1939373 TI - Smooth muscle alpha-actin is a marker for hair follicle dermis in vivo and in vitro. AB - We have examined the expression of smooth muscle alpha-actin in hair follicles in situ, and in hair follicle dermal cells in culture by means of immunohistochemistry. Smooth muscle alpha-actin was present in the dermal sheath component of rat vibrissa, rat pelage and human follicles. Dermal papilla cells within all types of follicles did not express the antigen. However, in culture a large percentage of both hair dermal papilla and dermal sheath cells were stained by this antibody. The same cells were negative when tested with an antibody to desmin. Overall, explant-derived skin fibroblasts had relatively low numbers of positively marked cells, but those from skin regions of high hair-follicle density displayed more smooth muscle alpha-actin expression than fibroblasts from areas with fewer follicles. 2-D SDS-PAGE confirmed that, unlike fibroblasts, cultured papilla cells contained significant quantities of the alpha-actin isoform. The rapid switching on of smooth muscle alpha-actin expression by dermal papilla cells in early culture, contrasts with the behaviour of smooth muscle cells in vitro, and has implications for control of expression of the antigen in normal adult systems. The very high percentage of positively marked cultured papilla and sheath cells also provides a novel marker of cells from follicle dermis, and reinforces the idea that they represent a specialized cell population, contributing to the heterogeneity of fibroblast cell types in the skin dermis, and possibly acting as a source of myofibroblasts during wound healing. PMID- 1939374 TI - The synthesis of type X collagen by bovine and human growth-plate chondrocytes. AB - Chondrocytes were isolated from bovine growth-plate cartilage and cultured within type I collagen gels. A major collagen with chains of Mr 59,000, decreasing to 47,000 on pepsinization, was synthesized and identified as type X collagen. This collagen was cleaved at two sites by mammalian collagenase, resulting in a major triple-helical fragment with chains of Mr 32,000. The species of Mr 59,000, 47,000 and 32,000 were not detected by SDS-polyacrylamide gel electrophoresis before reduction, indicating the presence of disulphide bonds within the triple helix. In contrast, similar biosynthetic studies with human growth-plate cartilage in organ culture, indicated that human type X collagen does not contain disulphide bonds. A polyclonal antiserum was raised to bovine type X collagen and used in immunolocalization studies to provide direct evidence for the association of type X collagen with the hypertrophic chondrocytes in both bovine and human growth plates during development. PMID- 1939375 TI - Transferrin gene expression and transferrin immunolocalization in developing foetal rat lung. AB - In previous studies we have shown that transferrin (Tf) specifically stimulates dermatan- and chondroitin-sulphate proteoglycan accumulation around lung cells, and in the extracellular matrix of lung tissue, in vitro. The aim of this study was to determine whether the gene for Tf was activated in specific lung cells during development, and whether the protein product showed evidence of association with extracellular matrix. The expression of the gene in developing lung was shown by the hybridization of a Tf cDNA to a 2.4 kb (kilobase) mRNA species in total RNA extracts of foetal lung. The expression of the Tf gene in comparison to a control gene (GAPD, glyceraldehyde phosphate dehydrogenase) was greatest in 19, 20 and 21 day foetal lung, rising from low levels on day 18 and decreasing markedly at term (day 22). Extracts of RNA from primary cultures of mesenchymal fibroblasts and type II epithelial cells were also analysed for Tf mRNA. These experiments indicated that Tf gene expression was predominantly confined to the mesenchymal compartment. The presence of Tf in histological sections of foetal lung was demonstrated by immunohistochemistry and showed a distinct pattern, with intense staining of the alveolar and the capillary basement membranes. The matrix surrounding the mesenchymal fibroblasts was stained in a diffuse network while epithelial cells were unstained. The staining was low from days 12-16 of gestation, increased to a maximum at days 19-20 but decreased markedly toward term. The Tf staining did not co-localize with transferrin receptor, also demonstrated by immunohistochemistry. These results suggest that Tf is not only present at specific sites in the developing lung, but also is synthesized according to a strict developmental schedule of gene expression. PMID- 1939376 TI - Extracellular matrix adhesion-promoting activities of a dermatan sulfate proteoglycan-associated protein (22K) from bovine fetal skin. AB - A 22 x 10(3) Mr protein (abbreviated 22K) that copurifies with dermatan sulfate proteoglycans (DS-PGs) following the biochemical fractionation of bovine fetal skin has been evaluated for adhesion-promoting activity in vitro using Balb/c 3T3 cells, as well as bovine and human dermal fibroblasts. Substrata coated with 22K protein promote attachment of a subset of 3T3 and dermal fibroblasts that respond to plasma fibronectin (pFN) substrata. Cells on 22K protein display partial cytoplasmic spreading, comparable to that of cells adhering to cell-binding fragments of pFN. Adhesion activity of 22K is not due to contamination with known adhesive proteins of dermal matrices and is not dermal cell type-specific, since two classes of neuronal cells also respond effectively to 22K substrata. DS-PGs from cartilage or skin completely inhibit 22K adhesion activity when the PGs are adsorbed to 22K substrata under conditions prohibiting PGs from binding to substrata directly. Cartilage chondroitin/keratan sulfate proteoglycan at much higher concentrations is only partially inhibitory. Inhibition by DS-PGs is mediated by DS chains binding to 22K. Properties of the cell surface 'receptor' for 22K protein were tested by several approaches. It is not cell surface DS-PG, since: (1) cells unable to produce this proteoglycan class also responded; (2) cells treated with chondroitinase ABC responded equally well; and (3) substrata of proteoglycan-binding platelet factor-4 generated responses from cells that were quantitatively and qualitatively different. A synthetic peptide in the medium containing the Arg-Gly-Asp-Ser (RGDS) sequence completely inhibited responses to 22K substrata. This observation, coupled with sequencing data of 22K protein revealing an Arg-Gly-Ala-Thr sequence at residues 151-154, suggest that 22K protein mediates adhesion by cell surface integrin binding. Therefore, this newly discovered matrix protein from skin may serve as a communication link between the dermal fibroblast cell surface and its extracellular matrix environment. PMID- 1939377 TI - Graded postischemic reoxygenation ameliorates inhibition of cerebral cortical protein synthesis in dogs. AB - The purpose of this study was to determine the effect of normoxic reperfusion and graded postischemic reoxygenation on cerebral protein synthesis in a cell-free system. Ischemia alone produced a relatively small decrease (15-17%) in activity in all the subcellular systems studied. After a 15-min interval of normoxic reperfusion (75-90 mmHg O2 in arterial blood), a 40% decrease (p less than 0.01) in [14C]leucine incorporation was observed. Reoxygenation with hypoxemic blood containing 37.5 mm Hg O2 at 0-5 min and 56 mm Hg O2 at 6-10 min of recirculation followed by 5 min of normoxic reperfusion resulted in a significant increase (p less than 0.05) of polypeptide chain synthesis in vitro when compared with normoxic reperfusion. The results obtained by this experimental approach tend to show that graded postischemic reoxygenation could be used as a simple and effective neuroprotective tool that substantially diminishes the secondary postischemic damage in nervous tissue, including the newly synthesized proteins. PMID- 1939378 TI - Insulin attenuates ischemic brain damage independent of its hypoglycemic effect. AB - Insulin, an endogenously produced circulating peptide that enters the brain, has been shown to reduce ischemic brain and spinal cord damage in several animal models. Because of its potential clinical use in humans, the present study was undertaken to test the hypotheses that (a) survival and regional ischemic brain necrosis are improved by insulin; (b) insulin requires concomitant hypoglycemia to exert its neuroprotective effect; (c) insulin is still neuroprotective with delayed administration after an episode of postischemic hypotension; and (d) insulin is beneficial after normoglycemic, as well as hyperglycemic ischemia. Rats were subjected to 10.5 min two-vessel occlusion forebrain ischemia followed by 30 min of hypotension to increase the infarction rate. Insulin administered concomitantly with glucose significantly reduced the seizure rate, as well as cortical and striatal neuronal necrosis below that seen in untreated animals. Neuroprotection was seen whether insulin was given before or after a 30-min episode of postischemic hypotension. Insulin reduced pan-necrosis in addition to selective neuronal necrosis: The infarction rate was reduced in the cerebral cortex, thalamus, and substantia nigra pars reticulata. Normoglycemic ischemia produced only selective neuronal necrosis, but a beneficial effect on structural damage was also seen. The results indicate that insulin acts directly on the brain, independent of hypoglycemia, to reduce ischemic brain necrosis. Possible direct CNS mechanisms of action include an effect on central insulin receptors mediating inhibitory neuromodulation, an effect on central neurotransmitters, or a growth factor effect of insulin. PMID- 1939379 TI - Protection after transient focal cerebral ischemia by the N-methyl-D-aspartate antagonist dextrorphan is dependent upon plasma and brain levels. AB - Dextrorphan is a dextrorotatory morphinan and a noncompetitive N-methyl-D aspartate (NMDA) receptor antagonist. We studied the dose response characteristics of dextrorphan's neuroprotective efficacy and side effects, correlating these beneficial and adverse responses with plasma and brain levels in a rabbit model of transient focal cerebral ischemia. Thirty-three rabbits, anesthetized with halothane, underwent occlusion of the left internal carotid and anterior cerebral arteries for 1 h, followed by 4.5 h of reperfusion. One hour after the onset of ischemia, they were treated with an i.v. infusion of varying dextrorphan doses or normal saline. After killing, the brains were analyzed for ischemic high signal intensity using magnetic resonance imaging (MRI) and for ischemic neuronal damage with histopathology. A separate group of 12 anesthetized ischemic rabbits received similar doses of dextrorphan, correlating plasma with brain dextrorphan levels. Twenty-six additional dextrorphan unanesthetized, nonischemic rabbits received infusions of dextrorphan to correlate behavioral side effects with dextrorphan dose and levels. Compared with controls, dextrorphan 15 mg/kg group had significantly less cortical ischemic neuronal damage (5.3 versus 33.2%, p = 0.01) and a reduction in cortical MRI high signal area (9.1 versus 41.2%, p = 0.02). The dextrorphan 10 mg/kg rabbits showed less cortical ischemic neuronal damage (27.2%) and less MRI high signal (34.8%) but this was not statistically significant (p = 0.6). Dextrorphan 5 mg/kg had no benefit on either neocortical ischemic neuronal damage (35.8%) or MRI high signal (42.9%). The protective effect of dextrorphan was correlated with plasma free dextrorphan levels (r = -0.50, p less than 0.02 for ischemic neuronal damage; r = -0.66, p less than 0.001 for ischemic MRI high signal). All the rabbits with plasma levels greater than 2,000 ng/ml had less than 12% cortical ischemic neuronal damage and less than 34% MRI high signal. All rabbits with plasma levels greater than 3,000 ng/ml showed less than 7% ischemic neuronal damage and less than 11% MRI high signal. Plasma levels of approximately 2,500 ng/ml correlated with brain dextrorphan levels of approximately 6,000 ng/g. Unanesthetized rabbits with plasma levels of approximately 2,500 ng/ml demonstrated loss of the righting reflex. These results demonstrate that systemic treatment with dextrorphan after 1 h focal ischemia can significantly protect against cerebral damage if adequate plasma and brain levels of dextrorphan are achieved. The brain levels necessary to obtain in vivo protection are similar to concentrations that prevent glutamate or NMDA-induced injury in neuronal culture. PMID- 1939380 TI - Reduction of infarct volume by magnesium after middle cerebral artery occlusion in rats. AB - The effects of magnesium, an endogenous inhibitor of calcium entry into neurons, upon ischemic brain damage were investigated using a well-characterized model of focal cerebral ischemia in rats. Infarct volumes were determined by 2,3,5 triphenyltetrazolium chloride transcardiac perfusion 48 h after middle cerebral artery (MCA) occlusion. The area of ischemic damage was quantified by image analysis in coronal sections taken every 0.5 mm. MgCl2 (1 mmol/kg) was injected intraperitoneally just after MCA occlusion and again 1 h later. Posttreatment with MgCl2 (16 control and 16 treated rats) significantly reduced the cortical infarct volume. Compensation for the hyperglycemic effect of MgCl2 with insulin (17 rats) further reduced the infarct volume in the neocortex. No systemic effects of either treatment could account for the observed neuroprotection. PMID- 1939381 TI - Cerebral blood flow reactivity to changes in carbon dioxide calculated using end tidal versus arterial tensions. AB - We retrospectively examined arerial and end-tidal estimations of CO2 tension used to calculate cerebrovascular reactivity in 68 anesthetized patients. CBF was measured using the intravenous 133Xe technique at mean +/- SD PaCO2 values of 28.2 +/- 5.2 and 38.8 +/- 4.8 mm Hg. The correlation between all PaCO2 and end tidal PCO2 (PetCO2) values was y = 0.85x - 0.49 (r = 0.93, p = 0.0001). There was a moderate correlation between age and the difference between PaCO2 and PetCO2 (y = 0.11x + 0.79; r = 0.73, p = 0.0001). Cerebrovascular reactivity to changes in CO2 (ml 100 g-1 min-1 mm Hg-1) was similar (p = 0.358) when calculated by using either PaCO2 (1.9 +/- 0.8) or PetCO2 (1.8 +/- 0.8) and highly correlated (y = 0.86x + 0.23; r = 0.91, p = 0.0001). The CBF response to changes in CO2 tension can be reliably estimated from noninvasive measurement of PetCO2. PMID- 1939382 TI - Safety of hypercapnic challenge: cardiovascular and neurologic considerations. AB - The hemodynamic, cerebrovascular, and neurologic effects of hypercapnia with 4% and 6% CO2 were retrospectively reviewed in 217 patients referred for regional CBF (rCBF) procedures. Inhalation of CO2 significantly increased rCBF, blood pressure, and pulse from baseline. The findings suggest a higher incidence of side effects with 6% CO2 concentration and an equivalent vasoreactivity to 4%. We recommend the use of 4% CO2 for hypercapnic stimulation, and present safety guidelines for its use. PMID- 1939383 TI - Louis Sokoloff at three score and ten. PMID- 1939384 TI - L-6-[18F]fluoro-dopa metabolism in monkeys and humans: biochemical parameters for the formulation of tracer kinetic models with positron emission tomography. AB - Characterization of peripheral and cerebral L-3,4-dihydroxy-6 [18F]fluorophenylalanine (FDOPA) metabolism in humans and monkeys has shown FDOPA to be an analogue of L-DOPA for the study of the dopaminergic system with positron emission tomography (PET). In human studies with carbidopa pretreatment, L-3,4-dihydroxy-6-[18F]fluoro-3-O-methylphenylalanine (3-OMFD) was the only FDOPA metabolite detected in plasma. FDOPA administration in monkeys resulted in selective accumulation of FDOPA metabolites in central dopaminergic regions, whereas 3-OMFD of peripheral origin was uniformly distributed among putamen, caudate, frontal cortex, and cerebellum. At 60 min, 3-OMFD and 6 [18F]fluorodopamine (FDA) each represented approximately 35% of the total activity, the remainder being FDOPA and FDA metabolites. These data on monkey and human FDOPA metabolism provide the basis for the configuration of an FDOPA tracer kinetic model with PET. PMID- 1939385 TI - Kinetics and modeling of L-6-[18F]fluoro-dopa in human positron emission tomographic studies. AB - Kinetics of L-3,4-dihydroxy-6-[18F]fluorophenylalanine (FDOPA) in striatum and cerebellum were measured in 10 normal human subjects with positron emission tomography (PET) from 0 to 120 min after an intravenous bolus injection of the tracer. The time course of the arterial plasma concentrations of the tracer and its metabolites was also assayed biochemically. FDOPA compartmental models that are based on biochemical information were investigated for their consistency with the measured striatal and cerebellar tissue kinetics. A modeling approach was also developed for separating plasma FDOPA and metabolite time-activity curves from the measured total 18F time-activity curve in plasma. Results showed that a model consisting of three separate compartments for tissue FDOPA, tissue 6 [18F]fluorodopamine (FDA) and its metabolites, and tissue L-3,4-dihydroxy-6 [18F]fluoro-3-O-methylphenylalanine (3-OMFD) could describe adequately the striatal kinetics in humans. Based on this model, the FDOPA transport constant across the blood-brain barrier (BBB) (K1), the FDOPA decarboxylation rate constant (k3), and the turn-over rate constant of FDA and its metabolites (k4) could be estimated by model fitting to the tissue kinetics and were found for the normal subjects to be 0.031 +/- 0.006 ml/min/g (mean +/- SD), 0.041 +/- 0.015/min, and 0.004 +/- 0.002/min, respectively. About 50% of the FDOPA that crossed the BBB from plasma to striatum was decarboxylated. The decarboxylation constant with respect to plasma FDOPA (K3) was 0.015 +/- 0.003 ml/min/g. The BBB transport corresponded to a permeability-surface area product of 0.032 ml/min/g for FDOPA. For 3-OMFD, the BBB transport was 1.7 times faster. The effects of tissue heterogeneity on the FDOPA kinetics and on the estimated model parameters were also investigated. The usefulness and implications of these findings for interpretation of PET FDOPA studies are discussed. PMID- 1939386 TI - Rapid feasibility studies of tracers for positron emission tomography: high resolution PET in small animals with kinetic analysis. AB - The development of methods for production of a radiotracer for use in human studies with positron emission tomography (PET) is often a time-consuming process of optimizing radiolabelling yields and handling procedures. Sometimes the radiotracer is not the original drug, but rather a derivative with unknown in vivo pharmacological properties. We have developed a fast and simple method of testing putative new PET tracers in vivo in small animals. The procedure has been validated in rats with different PET tracers with known kinetic and pharmacological properties ([2-18F]2-fluoro-2-deoxy-D-glucose, [N-methyl-11C]Ro 15-1788, and [15O]butanol). The tracer concentration in arterial blood was continuously measured to obtain the brain input function. Following image reconstruction of the scans, time-activity curves of selected regions of interest were generated. Estimations of CMRglc (1.0 +/- 0.2 mumol g-1 min-1), CBF (1.4 +/- 0.4 ml g-1 min-1) and transport rate constants for [N-methyl-11C]Ro 15-1788 (K1 = 0.44 +/- 0.01 ml g-1 min-1 and k2 = 0.099 +/- 0.005 min-1) as well as calculated first pass extraction (0.32 +/- 0.1) are in reasonable agreement with literature values. Small animal studies require minimal amounts of radioactivity and can be performed without sterility and toxicology tests. They may serve as a preliminary basis for radiation safety calculations because whole body scans can be performed even with a head scanner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939387 TI - Prepro-vasoactive intestinal polypeptide-derived peptide sequences in cerebral blood vessels of rats: on the functional anatomy of metabolic autoregulation. AB - This study describes the distribution of peptide sequences derived from the prepro-vasoactive intestinal polypeptide (preproVIP) molecule in perivascular nerves of rat brain arteries and arterioles. The peptides were identified by immunohistochemistry using highly specific antibodies. Five peptide sequences (preproVIP 60-76, peptide histidine isoleucine (PHI), preproVIP 111-122, VIP, and preproVIP 156-170) were identified in the perivascular nerves throughout the arterial cerebral circulation. The density of the immunoreactive fibers was highest in the nerves of the larger extracerebral arteries, declining in smaller branching arteries. All peptide sequences were identified in the nerves of small pial arterioles overlying the cortical convexity, whereas capillaries and veins contained no immunoreactive material. Dendritic processes of neocortical neurons immunoreactive for VIP and PHI could be followed towards the brain surface where the processes penetrated into the pial layer, often close to the pial vasculature. Some of the processes were also observed to enter the Virchow-Robin space, close to the arterioles. It is possible that cortical nerve cells containing VIP and PHI release the peptides in the perivascular space during periods of activity and thereby contribute to local vasodilatation associated with changes of neuronal function. PMID- 1939388 TI - A new method for producing temporary complete cerebral ischemia in rats. AB - A new model of temporary complete cerebral ischemia was developed and tested in 64 rats. With use of microsurgical techniques, both pterygopalatine and external carotid arteries were occluded and the basilar artery was coagulated to reduce potential collateral CBF during ischemia. After this preliminary five-vessel occlusion, temporary global ischemia was induced by occluding the common carotid arteries (CCAs) with microclips. To validate the method, CBF was measured autoradiographically in 24 anatomical regions at death after 5 min of ischemia or after 15 min of ischemia followed by 5 min of reperfusion. Mean arterial blood pressure and arterial blood gases remained stable under controlled endotracheal ventilation and anesthesia (halothane, 70% N2O, and 30% O2) throughout the CBF experiments, except for a 10-15% increase in mean arterial blood pressure for 1-5 min after bilateral CCA occlusion. After the initial five-vessel occlusion, the EEG did not change, and local CBF levels were comparable to those in anesthetized non-surgical controls. When the CCAs were occluded, the EEG flattened rapidly; after 5 min of ischemia, autoradiography showed no detectable blood flow in the forebrain and cerebellum. The local CBF levels measured after 15 min of temporary global ischemia and 5 min of reperfusion demonstrated relatively homogeneous postischemic hyperperfusion; only two of eight rats had several 1- to 3-mm areas of no-reflow. Survival studies showed increasing motor impairment after 10, 15, 30, and 60 min of temporary CCA occlusion. Ischemic neuronal damage was observed histologically in the hippocampus and basal ganglia 24 h after 10 min of temporary ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939389 TI - Hemodynamic consequences of common carotid artery thrombosis and thrombogenically activated blood in rats. AB - We documented the hemodynamic consequences of nonocclusive common carotid artery thrombosis (CCAT) and tested the hypothesis that vasoactive substances capable of altering local CBF (LCBF) are released into the systemic circulation following cerebrovascular injury. Ten minutes after photochemically induced CCAT, an autoradiographic determination of LCBF was conducted with [14C]iodoantipyrine. In blood transfusion studies using donor and recipient rats, a 1-ml sample of thrombogenically activated blood (TAB) collected downstream from the forming thrombus was reinjected into a recipient rat 15 or 60 min before CBF study. A heterogeneous pattern of abnormal LCBF was documented in the ipsilateral hemisphere of CCAT rats and recipient rats receiving TAB 15 min before CBF study. Acute hemodynamic abnormalities included ischemic (less than 35% of control) and hyperemic (greater than 125% of control) foci and more global reductions (50-80% of control) in cortical and subcortical LCBF. Border zone hyperemia exceeding 2.0 ml/g/min was associated with focal sites of severe LCBF reductions. Although recipient rats that received TAB 15 min before CBF study displayed similar hemodynamic abnormalities, LCBF values in 60-min recipient rats were not significantly different from control despite ischemic foci. Humoral factors generated during CCAT appear to be responsible for the acute LCBF consequences of cerebrovascular thrombosis. Vasoactive substances released from a thrombotic site, capable of regionally affecting vascular reactivity in a time-dependent fashion, might be expected to participate in the pathogenesis of transient ischemic attacks and acute stroke. PMID- 1939390 TI - Hippocampal damage following repeated brief hypotensive episodes in the rat. AB - We examined the brain damage following repeated hypotensive episodes in the rat. Severe hypotension was induced by withdrawal of arterial blood. The MABP was maintained at about 25 mm Hg with isoelectric EEG and the shed blood was retransfused. After 1 week of recovery, histopathological changes were examined. No brain damage was observed after 1 min of isoelectric EEG. Mild neuronal damage to the hippocampal CA1 subfield was seen in some animals after two episodes of 1 min isoelectric EEG at a 1-h interval. Significant and consistent neuronal loss in the hippocampal CA1 subfield was observed after three episodes of 1-min isoelectric EEG. Scattered neuronal damage in the thalamus was additionally seen in some animals. The present study indicates that repeated brief hypotensive episodes produce brain damage depending on the number of episodes, even though no brain damage results when induced as a single insult. This animal model may reproduce hemodynamic transient ischemic attacks in humans. PMID- 1939391 TI - Modulation of ornithine decarboxylase mRNA following transient ischemia in the gerbil brain. AB - Ornithine decarboxylase (ODC) is the rate-limiting enzyme that catalyzes the synthesis of polyamines from ornithine and is thought to be involved in the cellular response to growth, differentiation, and stress. Previous studies have demonstrated that transient cerebral ischemia results in an increase in ODC activity and polyamine synthesis. We have used the Mongolian gerbil as a model system to test the hypothesis that the cellular response to ischemia induces a distinct pattern of ODC gene expression. Our results indicate that transient ischemia, induced by bilateral carotid occlusion, elevates ODC mRNA within 1-4 h after reperfusion, which correlates with increased ODC activity and polyamine synthesis. Increased ODC mRNA can be detected in the forebrain, striatum, hippocampus, and midbrain but not the cerebellum, which is not subject to ischemic injury. In contrast, c-fos mRNA increased by 15 min after reperfusion and actin mRNA did not demonstrate alterations in level after ischemia. Pentobarbital prevented the increase in ODC mRNA, whereas the glutamate antagonist MK-801 had no effect on the elevation of ODC gene expression after ischemia. We conclude that the ischemia-induced increase in ODC enzyme activity may be attributed in part to transcriptional activation of the ODC gene. PMID- 1939392 TI - Adenosine release and changes in pial arteriolar diameter during transient cerebral ischemia and reperfusion. AB - We utilized the closed cranial window technique in the anesthetized rat to determine changes in CSF concentrations of adenosine, inosine, and hypoxanthine and pial arteriolar diameter during transient (20 min) forebrain ischemia and reperfusion. After mock CSF under the cranial window was allowed to equilibrate with cerebral interstitial fluid, endogenous adenosine concentration was found to be 0.16 +/- 0.05 microM, while inosine and hypoxanthine were 0.35 +/- 0.17 and 1.23 +/- 0.47 microM, respectively. The concentration of adenosine in CSF increased 4.2-fold during ischemia and 13.8-fold during the first 5 min of reperfusion. Inosine and hypoxanthine concentrations were also significantly increased during ischemia and reperfusion. After 1 h of reperfusion, CSF adenosine and inosine levels had decreased from peak value but remained significantly above preischemic values. In contrast, hypoxanthine remained at peak concentrations even after 60 min of reperfusion. Preischemic arteriolar diameter was 42.6 +/- 11.3 microns and was not significantly changed after 20 min of ischemia. However, during the first 5 min of reperfusion, arteriolar diameter increased significantly (p less than 0.05), coincident with peak adenosine concentrations. By 60 min of reperfusion, arteriolar diameter had returned to baseline. These results indicate that during the postischemic period, adenine nucleosides and hypoxanthine in CSF are elevated and could affect reperfusion. PMID- 1939393 TI - The contribution of reoxygenation to ischemic brain damage. AB - This study examined the hypothesis that the level of postischemic reperfusion affects the severity of the resulting neuronal necrosis. In rats, tissue PO2% was monitored as an index of flow (reoxygenation) at four cortical sites by chronically implanted platinum electrodes. Twenty minutes of total global cerebral ischemia was followed by 30 min of reoxygenation. The level of reoxygenation was controlled to maintain the PO2 nearly constant at one or more of the cortical electrodes. Tissue from within 400 microns of each of 19 electrode sites among seven rats was evaluated histologically. There was a positive correlation between reoxygenation level and severity of neuronal damage. Perineuronal lucent halo formation, probably representing astrocyte foot process swelling, was negatively correlated with reoxygenation level. This study demonstrates that ischemic neuronal damage was aggravated by increased reoxygenation but that perineuronal swelling, as evidenced by halo formation, was somewhat ameliorated. PMID- 1939394 TI - A stereochemically accurate chemical substance database based on the systematic names of organic compounds. 1. Low molecular weight organic compounds. AB - A chemical substance database, containing chemical structures generated automatically from their IUPAC systematic names, is described. The structure generation program can convert the names of natural products, peptides, and stereochemically complex names into stereochemically correct connection tables. More than 300,000 commonly encountered compounds are stored in the database and are publicly accessible through the JOIS-F online system, which also offers mass spectral, thermochemical, and other factual databases. PMID- 1939395 TI - MAPOS: a computer program for organic synthesis design based on synthon model of organic chemistry. AB - The program MAPOS is a logically oriented computer program for computer-aided organic synthesis design suitable both for forward and retrosynthetic synthesis planning. It is based on the synthon model of organic chemistry, introduced by the authors. The fundamentals of the model as well as the basic algorithms are described. Examples of the use of the program are given. PMID- 1939396 TI - Fast drug-receptor mapping by site-directed distances: a novel method of predicting new pharmacological leads. AB - The searching and characterization of large chemical databases has recently provoked much interest, particularly with respect to the question of whether any of the compounds in the database could serve as new leads to a compound of pharmacological interest. This paper introduces a fast and novel method of determining whether any of a given series of compounds are able, on geometrical grounds, to interact with an active site of interest. The C program written to implement the method is able to make a qualitative prediction for a given compound in about 1 s per structure (for drug-sized molecules), while still permitting the compound complete conformational freedom. However, the algorithm is sufficiently flexible to permit distance constraints to be placed on the molecules while docking. The test system studied was a family of Baker's triazines docking into the active site of dihydrofolate reductase (DHFR), as defined by a methotrexate/NADPH complex. PMID- 1939397 TI - Computer-assisted infrared identification of vapor-phase mixture components. AB - The IRBASE/MIXIR system was originally tested on interpretation of infrared spectra of condensed-phase mixtures. The system has now been adapted to allow interpretation of vapor-phase mixture spectra. The dynamic interpretation capabilities of the system have been expanded to allow runtime manipulation of complete peak lists, allowing generation of the optimum spectral description for the interpretation at hand. The modifications to the system are described, along with the results of testing on actual mixtures of varying complexity. PMID- 1939398 TI - THERM: a computer code for estimating thermodynamic properties for species important to combustion and reaction modeling. AB - A computer package has been developed called THERM, an acronym for THermodynamic property Estimation for Radicals and Molecules. THERM is a versatile computer code designed to automate the estimation of ideal gas phase thermodynamic properties for radicals and molecules important to combustion and reaction modeling studies. Thermodynamic properties calculated include heat of formation and entropies at 298 K and heat capacities from 300 to 1500 K. Heat capacity estimates are then extrapolated to above 5000 K, and NASA format polynomial thermodynamic property representations valid from 298 to 5000 K are generated. This code is written in Microsoft Fortran version 5.0 for use on machines running under MSDOS. THERM uses group additivity principles of Benson and current best values for bond strengths, changes in entropy, and loss of vibrational degrees of freedom to estimate properties for radical species from parent molecules. This ensemble of computer programs can be used to input literature data, estimate data when not available, and review, update, and revise entries to reflect improvements and modifications to the group contribution and bond dissociation databases. All input and output files are ASCII so that they can be easily edited, updated, or expanded. In addition, heats of reaction, entropy changes, Gibbs free-energy changes, and equilibrium constants can be calculated as functions of temperature from a NASA format polynomial database. PMID- 1939399 TI - An integrated approach to three-dimensional information management with MACCS-3D. AB - In the past decade, the scientific community has realized the value of three dimensional (3D) structural information and '3D searching' has started to become an important new methodology for computer-aided drug design. During this time, molecular modeling information generated from various sources has proliferated due to the growing availability of software and hardware and the increasing use of crystallographic and spectroscopic techniques. This information needs to be organized to allow for its effective storage and retrieval. This paper presents an approach to address this problem with a recently introduced program, MACCS-3D. In particular, this approach utilizes MACCS-3D's capability of handling data specific for atoms and atom pairs. With this software, various biological, computational, and spectroscopic data can be merged, allowing scientists from different disciplines to access and use this information more efficiently. PMID- 1939400 TI - Sticks, stones and names can hurt you--reflections on language and illness. PMID- 1939401 TI - The placebo shrine. PMID- 1939402 TI - The long-term risks and benefits of hormone replacement therapy. AB - There is increasing awareness that the long-term consequences of ovarian failure can be prevented or reduced with appropriate hormone replacement therapy (HRT). After the menopause, there is a rapid loss of trabecular bone resulting in a one in two lifetime risk of osteoporotic fracture. HRT prevents this bone loss and decreases the incidence of fracture. A minimum of 5 years treatment is recommended for significant benefit. Epidemiological evidence is accumulating that post-menopausal oestrogen therapy reduces the risk of cardiovascular disease and stroke by between 30 and 70% even in the presence of established risk factors. Given the prevalence of cardiovascular disease, this is likely to be one of the principle benefits of HRT in the next decade. Concerns about the long-term safety of HRT have focused on endometrial and breast cancer. The increase in risk of endometrial cancer associated with oestrogen only therapy is abolished with the sequential addition of a progestogen for 10-12 days each cycle. The possible effect of HRT on breast cancer risk has to be considered against the background of a one in 12 lifetime risk of developing this disease. The epidemiological studies investigating this relationship are reviewed in this paper. There is a broad consensus that 5-6 years duration of HRT does not increase breast cancer risk. Longer durations of therapy (10-15 years) have been reported to increase this risk although not all the data are in agreement. Other factors, such as family history and benign breast disease, may also influence the risk of breast cancer. The potential benefits of HRT on mortality and morbidity are enormous. Against this is a possible small increase in breast cancer risk with long-term usage. Greater awareness of the long term consequences of the menopause and the potential benefits of HRT should be encouraged so that women can make informed decisions about their need for HRT. PMID- 1939403 TI - Simultaneous high performance liquid chromatographic determination of dapsone and monoacetyldapsone in human plasma and urine. AB - A rapid, specific and a one-stage protein precipitation method for simultaneous estimation of dapsone (DDS) and monoacetyldapsone (MAD) concentration in plasma and urine using high performance liquid chromatography (HPLC) is described. The applicability of the method for monitoring DDS and MAD blood levels in two different acetylator phenotype volunteers following the administration of 100-mg oral dose of DDS was shown. Cumulative urinary excretion of DDS and MAD were studied in the same volunteers. PMID- 1939404 TI - Simultaneous determination of carbamazepine and its major metabolites in human plasma and urine by HPLC. AB - A method is described for the analysis of carbamazepine and its major metabolites in biological fluids. The method uses a HPLC system based on a C18 Partisil column. The metabolites were extracted from chloroform in the presence of an internal standard. The method was specific, precise and reproducible. PMID- 1939405 TI - Gynaecomastia and heart failure--adverse drug reaction or disease process? AB - The presence of gynaecomastia was assessed in 444 male patients in order to determine the overall incidence of this condition. In addition, patients were assessed for liver function, age, weight, height and drug therapy, in an attempt to identify causative factors for the presence of gynaecomastia. The results indicate that there is a positive correlation between gynaecomastia and right and/or left cardiac failure. In addition, drug therapy with frusemide, amiloride and captopril was significantly correlated with an increased incidence of gynaecomastia in the study population; however this correlation was not present for either age or body weight index. These drugs are commonly used in the therapy of heart failure. This study highlights the difficulty of differentiating between whether or not pathology or drug therapy is the main contributing factor to a proposed adverse drug reaction. PMID- 1939406 TI - Serum concentrations of gentamicin in patients with myelomeningocele. AB - Gentamicin serum concentrations were studied in 18 paediatric and adult patients. The doses of gentamicin had to be adjusted for 6 of 18 patients to keep peak and trough serum concentrations below 8 and 2 micrograms/ml, respectively. Thus, serum concentrations monitoring of gentamicin may be useful to individualize doses in patients with myelomeningocele. Additional studies are needed to define specific dosage guidelines in patients of varying ages and disease severity for optimal therapy. PMID- 1939407 TI - Pharmacokinetics of intravenous caffeine in critically ill patients. AB - The pharmacokinetics of intravenous caffeine used to measure liver function were evaluated in 20 critically ill patients. Each patient received a single dose of 3.0 mg/kg of caffeine benzoate as a 30-min i.v. infusion. Caffeine serum concentrations were analysed by an enzyme-multiplied immunoassay technique (EMIT). Caffeine pharmacokinetics fitted an open one-compartment model. The mean value for the half-life (t1/2) was 9.46 +/- 4.32 h, the volume of distribution was 0.55 +/- 0.13 l/kg, and the plasma clearance (Cl) was 0.85 +/- 0.44 ml/min/kg. The pharmacokinetics parameters of caffeine in critically ill patients compared with normal volunteers were characterized by a reduction in plasma clearance and prolongation in plasma half-life, whereas the volume of distribution remained unchanged. PMID- 1939408 TI - Influence of age and concurrent medication on steady-state valproic acid serum level-dose ratios in Japanese paediatric patients. AB - The effects of age and co-medication on steady-state valproic acid (VPA) level/dose (L/D) ratios were evaluated retrospectively in 382 paediatric patients. The VPA L/D ratio increased significantly with age up to 15 years of age in patients on monotherapy (L/D = 0.149 x AGE + 2.708, n = 192, r = 0.549, P less than 0.001). In patients taking three or more anti-epileptic drugs, including VPA, there was no such effect. Associated anti-epileptic therapy affected the VPA L/D ratio, which was significantly reduced in patients on polytherapy as compared to patients on monotherapy. Therefore, routine monitoring of VPA serum levels would be extremely useful, especially in the paediatric age group, and in patients who require associated anti-epileptic medication. PMID- 1939409 TI - In-use life of levothyroxine sodium tablets. PMID- 1939410 TI - Multiple system organ failure and the sepsis syndrome. PMID- 1939411 TI - The GP/FP backbone. PMID- 1939413 TI - How mouse became a verb. PMID- 1939412 TI - The changing epidemiology of HIV transmission. AB - Globally, heterosexual transmissions are outdistancing all other categories and may account for 80% of HIV infections by the end of the decade. With rapid spread of the epidemic in southern and southeastern Asia, WHO projects that the total number of HIV-infected adults will reach 30 million by the year 2000, with an additional 10 million pediatric cases. PMID- 1939414 TI - John Hughlings Jackson and the evolution of modern neurology. PMID- 1939415 TI - A tennis player with a swollen calf. PMID- 1939416 TI - An anemia called pernicious. PMID- 1939417 TI - Extreme tachycardia in a kindergartner. PMID- 1939419 TI - Decision making. PMID- 1939420 TI - Hydrophilic-interaction chromatography of peptides on hydrophilic and strong cation-exchange columns. AB - Hydrophilic-interaction chromatography (HILIC) was recently introduced as a potentially useful separation mode for the purification of peptides and other polar compounds. The elution order of peptides in HILIC, which separates solutes based on hydrophilic interactions, should be opposite to that obtained in reversed-phase chromatography, which separates solutes based on hydrophobic interactions. Three series of peptides, two of which consisted of positively charged peptides (independent of pH at pH less than 7) and one of which consisted of uncharged or negatively charged peptides (dependent on pH), and which varied in overall hydrophilicity/hydrophobicity, were utilized to examine the separation mechanism and efficiency of HILIC on hydrophilic and strong cation-exchange columns. PMID- 1939418 TI - Neurologic presentations in Lyme disease. PMID- 1939422 TI - Silica versus polymer-based stationary phases for reversed-phase high-performance liquid chromatographic analyses of rat insulin biosynthesis. A comparison of resolution and recovery. AB - Because of the problems caused by the irreversible binding of insulins and proinsulins to several silica-based reversed-phase columns, the use of polymeric reversed-phase columns was investigated for the analysis of rat islet polypeptides involved in insulin biosynthesis. No irreversible binding of insulins and proinsulins was observed for the polymeric reversed-phase columns, probably due to the absence of silanol groups. The six polypeptides involved in insulin biosynthesis in rat islets were equally well resolved in shallow trifluoroacetic acid-acetonitrile gradients on the silica-based Nucleosil 300-5C4 column (45 degrees C), the polymer-based Asahipak C4P-50 (25 and 45 degrees C), and ODP-50 columns (45 degrees C). In shallow triethylammonium phosphate acetonitrile gradients (25 degrees C) satisfactory resolution of the two rat proinsulins was only obtained on the polymer-based Asahipak C4P-50 and C8P-50 columns. Increasing the separation temperature to 45 degrees C improved the separation of the two insulins and the two proinsulins in all cases. The shifts in retention times for the individual islet polypeptides observed in relation to the increased separation temperature were found to be different for the silica C4 and the polymer C4 columns. Recoveries of rat islet polypeptides were comparably high from the silica- and the polymer-based C4 columns and linear load-response curves were obtained in the microgram to picogram mass range on both columns. PMID- 1939421 TI - Characterization of synthetic macroporous ion-exchange resins in low-pressure cartridges and columns. Evaluation of the performance of Macro-Prep 50 S resin in the purification of anti-Klenow antibodies from goat serum. AB - Three ion-exchange materials and one hydrophobic-interaction chromatography packing, based on a rigid macroporous polymer with large, relatively uniform pores, have been evaluated for low-pressure liquid chromatography of antibodies. These sorbents have high capacities for both small and large proteins and are mechanically, chemically, and thermally stable. Macro-Prep 50 S. CM and Q ion exchange materials are strongly acidic, weakly acidic, and strongly basic, respectively. Protein binding and recovery, pressure-flow properties, and chemical and thermal stability were determined for each sorbent. A rapid, two step method for the purification of anti-Klenow antibodies from goat serum was developed, based on the Macro-Prep 50 S strong-acid cation-exchange material and the Econo-Pac HIC prepacked hydrophobic-interaction cartridge. PMID- 1939423 TI - Purification of Phleum pratense pollen extract by immunoaffinity chromatography and high-performance ion-exchange chromatography. AB - Basic allergens of Phleum pratense pollen extract have been purified by either sequence gel filtration-ion-exchange high-performance liquid chromatography (HPIEX) and size-exclusion HPLC or sequence gel filtration-immunoaffinity chromatography and HPIEX. The second procedure seems to be suitable for preparative purposes. PMID- 1939424 TI - A ten-residue fragment of an antibody (mini-antibody) directed against lysozyme as ligand in immunoaffinity chromatography. AB - The interaction between an antibody molecule and a protein antigen is an example of "natural" protein modelling. Amino acids of the antigen-binding site consisting of three hypervariable segments (L1, L2, L3) of the light (L) and three (H1, H2, H3) of the heavy (H) chain of an antibody molecule interact with amino acids present in an epitope of a protein. A ten-residue peptide was synthesized with an amino acid sequence analogous to the hypervariable L3 segment of a monoclonal antibody directed against lysozyme. The peptide was immobilized on CH-Sepharose 4B and the affinity adsorbent was used to purify lysozyme added to a detergent extract of insect cells infected with a recombinant baculovirus. This methodology may also be applicable to other antigen-antibody combinations, in immunoaffinity chromatography for selective purification of a protein or in an immunosensor for detection of a protein. PMID- 1939425 TI - Effect of antigen size on optimal ligand density of immobilized antibodies for a high-performance liquid chromatographic support. AB - The antigen binding capacities for purified polyclonal antibodies immobilized onto a silica-based high-performance liquid chromatographic (HPLC) affinity support are described for three serum proteins over a range of antibody ligand densities. The rate of decline in the specific activity of the immobilized antibodies with respect to increasing ligand density was found to increase with the molecular weights of the antigens. The antibodies used were purified from whole antiserum using high-performance affinity chromatography and were examined using HPLC on an SCX stationary phase. Conditions are also described for efficient coupling of the ligand to the support. PMID- 1939426 TI - Multi-column preparative reversed-phase sample displacement chromatography of peptides. AB - Preparative reversed-phase sample displacement chromatography (SDC) of peptides was examined utilizing a multi-column approach. The effects of various SDC run parameters (flow-rate, run time and sample load) on the distribution of a single purified peptide and a mixture of three synthetic peptides was examined. The peptides in the mixture were closely related in hydrophobicity and mixed in a 1:4:1 ratio designed to mimic a typical preparative separation problem frequently encountered in crude synthetic peptide mixtures, that is, where there exist both hydrophobic and hydrophilic synthetic impurities close to the product of interest. Based on the results of these model systems, a SDC protocol was applied to the preparative purification of a crude synthetic peptide. The multi-column SDC approach provides rapid separations that are easy to employ because isocratic elution is utilized both in the separation process and in elution of the column segments. There is minimal fraction analysis, minimal use of organic solvents and increased utilization of the stationary phase such that the method involves considerably lower costs than traditional gradient-elution chromatography. PMID- 1939427 TI - Glycosylation of extracellular superoxide dismutase studied by high-performance liquid chromatography and mass spectrometry. AB - Extracellular superoxide dismutase, EC-SOD, the main superoxide dismutase in biological fluids, is known from its lectin binding to be a glycoprotein. We have characterized the glycosylation of recombinant EC-SOD. A tryptic digest of the protein contained only one glycosylated peptide. This peptide was specifically bound to lectins and stained by periodic acid-Schiff stain. Although appearing very large on size-exclusion chromatography, it was shown to be glycosylated at only one site, asparagine-89, by specific cleavage with glycanases followed by mass spectrometry of the resulting peptide. Based on the binding properties of the peptide to concanavalin A and lentil lectin and the elution profile of N glycanase-treated glycopeptide on ion-exchange chromatography, the carbohydrate appears to be the complex biantennary type with a core fucose. PMID- 1939429 TI - Fingerprinting of molecular components in individual human cerebrospinal fluid samples with a new micropurification system. AB - This paper reports a rapid and sensitive microtechnique for fingerprinting as little as 20 microliters of cerebrospinal fluid (CSF) from individual humans. Different molecular components were also isolated from the fluid. The SMART system, a new system optimized for high-recovery micropurification, was used for this purpose. The CSF sample, obtained by lumbar puncture, was applied directly into the system, and the patterns recorded for different individuals under various physiological conditions were compared. The results indicate that the procedure provides a powerful tool for the identification or recovery of CSF components and may also be of importance for diagnostic use. PMID- 1939428 TI - Peptide maps at picomolar levels obtained by reversed-phase high-performance liquid chromatography and pre-column derivatization with phenyl isothiocyanate. Microsequencing of Phenylthiocarbamyl Peptides. AB - A new reversed-phase high-performance liquid chromatography approach to the production of analytical peptide maps by pre-column derivatization using phenylisothiocyanate is described. Tryptic peptide digests were derivatized with phenyl isothiocyanate to form the phenylthiocarbamyl peptides followed by reversed-phase high-performance liquid chromatographic analysis. The phenylthiocarbamyl peptides were separated by reversed-phase high-performance liquid chromatography with the conventional gradient elution system of water acetonitrile containing trifluoroacetic acid. The sensitivity of detection of these peptide derivatives was within the range 5-10 pmol with a constant baseline at 254-260 nm. The isolated phenylthiocarbamyl peptides can be subjected to automatic Edman degradation. The effectiveness of this method was exemplified by microsequencing of phenylthiocarbamyl peptides isolated from tryptic digests of three different proteins: alpha-lactalbumin, beta-lactoglobulin and a lambda light-chain immunoglobulin. PMID- 1939430 TI - High-performance liquid chromatographic determination of peptides in biological fluids by automated pre-column fluorescence derivatization with fluorescamine. AB - Peptides containing a free alpha- or epsilon-amino group react with fluorescamine under mild alkaline conditions to generate a highly fluorescent but unstable reaction product and, consequently, practical high-performance liquid chromatographic (HPLC) approaches to analysis have typically involved the use of postcolumn derivatization. An automated precolumn approach is reported in which peptides are reacted with fluorescamine just prior to HPLC analysis by a commercially available autoinjector with derivatization capabilities. The autoinjector added base and fluorescamine reagent solutions to a sample vial containing peptide analytes, and the derivatization reaction was allowed to proceed for 5 min at room temperature prior to injection into the HPLC system. The derivatized peptides were analyzed by reversed-phase HPLC with fluorescence detection (excitation at 390 nm; emission 470-nm cut-off filter) on an octylsilica column. Optimization of the precolumn reaction conditions and the use of narrower HPLC columns (2 mm I.D.) resulted in a typical on-column detection limit of 30-50 fmol of peptide, which was substantially lower than that in previously reported post-column methods. This approach was applied to the HPLC of several naturally occurring and synthetic peptides containing alpha- and epsilon amino groups. In combination with solid-phase extraction, prior to automated precolumn fluorescence derivatization and chromatographic analysis, the methodology was used for the determination of a synthetic growth hormone releasing peptide in plasma samples. PMID- 1939431 TI - Separation of acidic peptides by reversed-phase ion-pair chromatography. Analytical application to a series of acidic substrates of casein kinases. AB - A series of small peptides including clusters of glutamyl residues, synthesized to study the site specificity of rat liver (L-CK2) and yeast (Y-CK2) casein kinase-2, are analytically characterized by ion-pair high-performance liquid chromatography using tetrabutylammonium as counter-ion and acetonitrile as modifier of the aqueous phase. Under these conditions peptides of slightly different acidity can be separated and the elution order parallels the hydrophobicity of the ion-pair-peptide complexes, which increases with the number of the acidic functions present in the sequence. PMID- 1939432 TI - Animal test or chromatography? Validated high-performance liquid chromatographic assay as an alternative to the biological assay for ornipressin. AB - Ornipressin is a peptide drug which is usually assayed by a test on live rats. In order to reduce the animal experiments an alternative method was developed which uses gradient high-performance liquid chromatography (HPLC) on reversed-phase. The HPLC method was validated and shown to be selective and precise. Correlation studies were performed on samples of different dosage strengths and on thermally degraded samples, showing good correlation with the results obtained by the biological assay. The HPLC method was applied on various batches of ornipressin in bulk and in pharmaceutical preparations. HPLC is a rapid and inexpensive method which can replace the animal assay. A new quality control concept is proposed which uses HPLC for the analysis of ornipressin in bulk and in pharmaceutical preparations. With this concept animal testing can be reduced by 90%. PMID- 1939433 TI - Non-radioactive detection of MHC class II-peptide antigen complexes in the sub picomole range by high-performance size-exclusion chromatography with fluorescence detection. AB - In order to avoid chemical or structural modification of T-cell epitopes by labelling, a high-performance size-exclusion chromatographic fluorescence binding assay was developed, based on the intrinsic Trp fluorescence of major histocompatibility complex (MHC) proteins. The increase in Trp fluorescence intensity of the isolated human MHC product HLA-DR 1 on complex formation with unlabelled influenza matrix peptide[18-29] (IM[18-29]) was examined. Binding of IM[18-29] to the heterodimeric form of HLA-DR 1 (Kd = 4.8 mM) and to the disassembled alpha-and beta-subunits (Kd = 9.2 mM) could be demonstrated. In addition, the assay showed the peptide-induced formation of a dimeric conformer of HLA-DR 1, the nature of which is still undefined. Detection of HLA-DR 1 subunit-peptide complexes was possible in amounts of 25 ng in 10 microliter (80 fmol/microliter). The technique proved to be reproducible and less time consuming than common methods that need fluorescence or radioactive labelling. PMID- 1939434 TI - Phenotyping of bovine milk proteins by reversed-phase high-performance liquid chromatography. AB - A reversed-phase high-performance liquid chromatographic method for the separation of the most common and some less common genetic variants of the bovine caseins is described. When the method is used for analysing clarified skim milk, simultaneous identification of casein variants and major they protein variants can be effected in a single run. The potential of the method for quantitative application is discussed. PMID- 1939435 TI - Separation and quantitation of serum proinsulin and proinsulin intermediates in humans. AB - Two reversed-phase high-performance liquid chromatographic (RP-HPLC) systems were developed for the separation of human insulin, proinsulin and the major proinsulin intermediates. The individual components were quantified using two enzyme-linked immunosorbent assays for insulin and proinsulin immunore-active material (PIM) after (passive) evaporation of the organic modifier. Serum samples from normal subjects and patients with non-insulin-dependent diabetes mellitus were immunopurified and analysed in one of the RP-HPLC systems. The proportion of PIM relative to insulin immunoreactive material was higher in the diabetic patient compared with that in the normal subject. In both, PIM was heterogeneous, consisting of intact proinsulin and des-proinsulin intermediates. PMID- 1939436 TI - Application of the split-peak effect to study the adsorption kinetics of human serum albumin on a reversed-phase support. AB - The adsorption step of human serum albumin on a reversed-phase support was analyzed by studying the "split-peak" effect in mass-overload conditions. This behavior is characterized by the occurrence of a first non-retained fraction and is described by an analytical expression in the case of a Langmuirian adsorption isotherm. The method was applied to determine the column loading capacity, the number of mass-transfer units and the apparent adsorption rate constant measured at a given flow-rate. The nature of the organic modifier influences the split peak effect: it increases with the eluotropic strength of the organic solvent added to the buffer. Compared to the results with pure buffer, it is the association of two effects, the decrease of the column loading capacity and that of the apparent adsorption rate constant, which increases the split-peak effects observed when methanol and 2-propanol are added to the eluent. These results allow us to gain a better understanding of the role of the organic solvent in the elution behavior of proteins in reversed-phase high-performance liquid chromatography. PMID- 1939437 TI - [High resolution gas phase chromatography-mass spectrometry of polychlorinated biphenyl congener residues in samples of biologic origin]. AB - A study is performed on polychlorinated biphenyl (PCB) congener residues in samples of human blood and milk as well as in falcon and pigeon eggs. Most of the PCB congeners found in these biological samples were quantified by high resolution gas chromatography (HRGC). A PCB technical mixture--namely, DP6 (Phenochlor)--was used for the calibration as its composition was previously determined by HRGC-mass spectrometry. The usefulness of such a congener analysis is outlined. It is the first time to the best of our knowledge that a Phenochlor mixture is used for standardization. PMID- 1939438 TI - Rapid method for the determination of organochlorine pesticides in milk. AB - This method involved one step solvent extraction of milk with ethyl acetate acetone-methanol by ultrasonication. The supernatants were further cleaned-up and enriched by solid-phase extraction using octadecyl (C18)-bonded silica cartridges, then assayed by capillary gas-liquid chromatography with electron capture detection. The recoveries of eleven organochlorine pesticides (OCPs) from raw milks were quantitative, ranging from 90-110% at 10 times the limit of detection (LOD). The LOD ranged from 0.5 micrograms/l whole milk for alpha hexachlorocyclohexane to 2.5 micrograms/l whole milk for 1,1,1-trichloro-2,2 bis(p-chlorophenyl)ethane. The day-to-day variation of the method was evaluated over 7 days using 3 different pools of spiked cow milks (at the LOD, 5 and 10 times the LOD). The coefficient of variations (C.V.s) were 16 +/- 6, 10 +/- 2 and 9 +/- 3% (mean S.D.), respectively. The method showed no emulsion problems common with conventional non-polar solvent extraction, and the use of solid-phase extraction considerably reduced the sample clean-up process compared with the existing methods. The method also showed that OCPs in milk could be extracted quantitatively without extraction of total fat, and that OCPs spiked into cows milk could be used to construct calibration curves for human milk determinations. PMID- 1939439 TI - Removal of organic pollutants from aqueous solution. V. Comparative study of the extraction, recovery and chromatographic separation of some organic insecticides using unloaded polyurethane foam columns. AB - The concentration of dissolved insecticides in aqueous media was determined by chromatographic separation on polyurethane foam columns. The results of preliminary screening tests on the removal of insecticides by the unloaded polyurethane foam indicated that a reasonable percentage of the insecticides was retained on the foam. Therefore attempts were made to extract these compounds from aqueous media using foam columns. Various parameters affecting the retention and separation of these compounds were studied, including temperature, flow-rate, pH, insecticide concentration, shaking time, sample volume and eluting solvent. The complete separation and quantitative recovery of these compounds from the foam with acetone in a Soxhlet extractor were achieved. The method can be used to preconcentrate insecticides in tap water and modified to determine dissolved insecticides in industrial and natural waters. Polyurethane foam has a good capacity for use when large volume samples need to be handled and is an inexpensive sorbent compared to other known solid sorbents. PMID- 1939441 TI - Chemically bonded phases for the reversed-phase high-performance liquid chromatographic separation of basic substances. AB - A chemically bonded phase with a peptide group (PB) for reversed-phase high performance liquid chromatography (HPLC) is described. This packing was prepared by a two-stage modification of the surface of silica gel with mono- and trifunctional 3-aminopropylsilane and then with an appropriate derivative of a fatty acid. Packings prepared in this way were compared with standard C18 materials used in HPLC. Surface characteristics of the packings before and after chemical modification were determined by different physico-chemical methods, e.g., porosimetry, elemental analysis, 13C and 29Si cross-polarization magic angle spinning NMR and HPLC. Chromatographic properties of these packings were evaluated by comparison between log k' of one phase and log k' of a second phase for substances with different chemical natures. The PB packing was found to be especially useful for the separation of basic substances. PMID- 1939440 TI - Bead cellulose derivatives as supports for immobilization and chromatographic purification of proteins. AB - Characteristic data are presented for Divicell, a macroporous bead cellulose with excellent flow parameters. The preparation of Divicell derivatives and their properties are described with respect to their application as chromatographic supports. The ion exchangers Divicell DEAE and Divicell CM were manufactured in two types with different exclusion limits and an available capacity for proteins of up to 100 mg/ml gel. Divicell Blue is a bead cellulose with covalently bound Cibacron Blue F3G-A and was found to be a very suitable adsorbent for the selective separation and purification of human serum albumin. Activation of Divicell with sodium periodate, epichlorohydrin and 5-norbornene-2,3 dicarboximido carbonochloridate provided activated supports used for immobilization of ligands in organic solvents and in aqueous solutions. Coupling of amines, diamines, amino acids, carbohydrates and proteins is described. The immobilized ligands retained their biological activity as determined by their specific adsorption of proteins. Divicell alkyl derivatives were tested in hydrophobic interaction chromatography with bovine serum albumin as a model. Examples are presented of the application of Divicell derivatives to the purification of biomacromolecules such as immunoglobulins and lectins by affinity chromatography. The results were comparable to those obtained using the corresponding Sepharose-derived absorbents. PMID- 1939442 TI - High-performance liquid chromatography in enzymatic analysis. Opening lecture. AB - During the previous two decades, high-performance liquid chromatography (HPLC) has proven to be an extremely useful technique with which to study the activity of enzymes and this paper will explore some of these uses. The success of the method can be seen not only from the increase in the number of papers utilizing this technique but also from the insights gained from its use on cellular phenomena. Given this success, it is no wonder that HPLC has become the technique of choice for many biologists seeking a more quantitative understanding of biological processes. Based on past experience, there is every reason to expect that the application of HPLC to the assaying of enzymatic activities will usher in another era of fundamental discoveries in the biological sciences. HPLC is particularly well suited to the assay of one activity in the presence of other activities obviating the need for extensive and tedious purification of biological samples. This advantage makes this technique particularly well suited to those who wish to use enzymes as markers for cellular processes, as indicators of metabolic activity and as evidence of gene function. To date, well over 100 activities have been assayed by this method. The method is particularly suited to problem-solving especially in such cases as when the presence of competing reactions prevents the recovery of the expected reaction products. Of the many applications, examples will be given on the use of HPLC for (1) monitoring the activity of an enzyme in a cell-free system, (2) monitoring the flow of metabolites through a multienzyme system and (3) the detection and study of new enzymatic activities. Some generalizations about the use of HPLC methods for the analysis of enzymatic activities will be presented. PMID- 1939443 TI - Application of high-performance liquid chromatography to the study of biogenic amine-related enzymes. AB - The application of high-performance liquid chromatography to the study of biogenic amine-related enzymes is reviewed. Biogenic amines include catecholamines (dopamine, norepinephrine and epinephrine), indoleamines (serotonin and melatonin), imidazoleamines (histamine), polyamines (putrescine, spermidine and spermine) and acetylcholine. Three particular aspects are covered. The first aspect is the assay of enzyme activities of biogenic amine-related enzymes, such as tyrosine hydroxylase, tryptophan hydroxylase, aromatic L-amino acid decarboxylase, dopamine beta-hydroxylase and phenylethanolamine N methyltransferase. The introduction of highly sensitive assays of biogenic amines with electrochemical detection or fluorescence detection have made possible the non-isotopic assay of these activities, replacing the previously used radioisotopic methods. The second aspect is the purification of these enzymes. Since biogenic amine-synthesizing enzymes are generally unstable, rapid and efficient purification of these enzymes is very useful. The third aspect is the assay of biogenic amines (for example, acetylcholine and polyamines) using post column derivatization with biogenic amine oxidases and electrochemical detection. PMID- 1939444 TI - Construction of kinetic models to understand metabolism in vivo. AB - This review describes increasingly complex kinetic models that simulate carbohydrate metabolism in a simple eucaryotic system which undergoes differentiation. Dynamic models of complex metabolic networks serve to organize and analyze the many interdependent variables involves and to define the rate limiting events controlling metabolism in vivo. Since the ultimate justification for and test of any model are its predictive values, a series of predictions and related experiments will be described. PMID- 1939445 TI - Automated high-performance liquid chromatographic assay of enzymatic activities. AB - High-performance liquid chromatography (HPLC) is a powerful technique which enables a reliable and quantitative determination of enzyme activities. The purpose of the work reported here was to develop an automatic assay of enzymatic activity. Using an automatic sample processor and injector, a program was developed which allows the complete automation of each step of analysis (calibration, enzymatic reaction, HPLC determination). This program can be adapted to different experimental requirements as each step can be performed independently and each input (time, volume, number of standards) is made by answering questions asked by instrument. Using this approach both kinetic and single-point determinations can be carried out, and in the latter case different samples can be analysed sequentially. This paper reports the automated analysis of trypsin. PMID- 1939446 TI - Direct injection high-performance liquid chromatographic method with electrochemical detection for the determination of ethanol and methanol in plasma using an alcohol oxidase reactor. AB - A highly sensitive reversed-phase high-performance liquid chromatographic assay for ethanol and methanol in plasma, using a post-column enzymic reactor with electrochemical detection, has been developed. The alcohols, separated on the column, were converted by immobilized alcohol oxidase into their respective aldehydes with formation of stoichiometric amounts of hydrogen peroxide, detected via oxidation at a platinum electrode. As the chromatographic column, two glass cartridges (150 mm x 3 mm I.D.) in series, packed with 10 microns HEMA-S 1000 packing, were used. Alcohol oxidase from Candida boidinii was immobilized onto HEMA-BIO 1000 VS-L (10 microns), packed in a 30 mm x 3 mm I.D. glass cartridge. The reaction product, hydrogen peroxide, was detected with an amperometric detector with a platinum electrode, operated at +500 mV vs. an Ag/AgCl reference electrode. A 20-microliters volume of ten-fold diluted plasma was injected without any pre-treatment. Under the described conditions, methanol and ethanol were well resolved from each other and from the "front" of the chromatogram. The limit of detection was ca. 2.5 nmol for ethanol and 0.6 nmol for methanol in plasma, at a signal-to-noise ratio of 3. Excellent linearity was observed for ethanol, in the range 0.125-4 micrograms injected (r = 0.9999). In contrast, the response for methanol was markedly non-linear above 500 micrograms injected, presumably owing to progressive saturation of the reactor. The precision and accuracy of the assay were satisfactory, as was the reactor life (one month). PMID- 1939447 TI - Carrier membrane as a stationary phase for affinity chromatography and kinetic studies of membrane-bound enzymes. AB - The use of membrane supports as stationary phase, coupled with ligands of choice, allows all kinds of chromatography [Dj. Josic, K. Zeilinger, Y. Lim, M. Raps, W. Hofmann and W. Reutter, J. Chromatogr., 484 (1989) 327] and offers a powerful alternative to both soft gel chromatography and high-performance liquid chromatography. In this work we present affinity membrane chromatography for purification of the enzyme carbonic anhydrase from haemolysates of human erythrocytes. Furthermore, the coupling of the enzymes to the membrane support allows kinetic investigations. As an example, kinetic experiments were carried out by means of carbonic anhydrase coupled to the membrane support using 4 nitrophenyl acetate and 2-chloro-4-nitrophenyl acetate as substrates. PMID- 1939448 TI - Purification of carbonic anhydrase isoenzymes by high-performance affinity chromatography and hydrophobic interaction chromatography. AB - Isoenzymes of carbonic anhydrase were purified by a combination of affinity chromatography and hydrophobic interaction chromatography. Immobilization of sulfonamides on an epoxy-activated support provided a stationary phase for affinity chromatography which was stable to hydrolysis by carbonic anhydrase. A first purification step allowed the isolation of enzymes directly from homogenates of human erythrocytes and rat stomach. Without any further preparation, except the addition of ammonium sulfate to the eluate from affinity chromatography, the isoenzymes could be separated by hydrophobic interaction chromatography with very high recovery of protein and retention of enzymatic activity. PMID- 1939449 TI - Immobilization of ultra-thin layer of monoclonal antibody on glass surface. AB - When preparing an affinity column and a biosensor, it is desirable to immobilize a unimolecular layer of pure protein on a matrix. In this work, we tried to immobilize a monoclonal antibody on a surface of a glass test-tube as a model, to confirm the stability of this ultra-thin layer by an enzyme immunoassay, and to estimate the thickness of the layer on a slide glass by Fourier transform infrared reflection spectrometry. A new test-tube was washed and dried. The tube was filled with 5% 3-aminopropyltriethoxysilane. The 3-aminopropylsilylated surface was treated with glutaraldehyde and 5.6.10(-2) mg/ml solution of a normal mouse monoclonal antibody. The Schiff base between glutaraldehyde and the antibody was further reduced with 7.9.10(-3)% NaBH4. The tube was washed with 0.05% Tween 20 to block non-specific binding. The antibody immobilized on the surface was measured by an enzyme immunoassay based on a reaction of anti-mouse immunoglobulin G labelled with alkaline phosphatase, with which p-nitrophenol was produced from p-nitrophenylphosphate as a substrate. Meanwhile, various amounts of the antibody were immobilized on slide glasses in the same manner. The antibody on each surface was measured by Fourier transform infrared reflection spectrometry. The antibody immobilized under the final conditions was detectable by the enzyme immunoassay, and stable at 4 degrees C for ten days. The antibody on the slide glass was a unimolecular layer, as judged from the Fourier transform infrared spectra referred to -CONH- band semiquantitatively. Thus, we found the optimal conditions for immobilizing an ultra-thin layer of the monoclonal antibody on the glass surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939450 TI - High-performance liquid chromatographic assay of human lymphocyte kynureninase activity levels. AB - Human lymphocyte kynureninase activity was assessed in homogenized cells by determination of 3-hydroxyanthranilic acid production as a function of time after addition of the substrate, 3-hydroxykynurenine. The product, 3-hydroxyanthranilic acid, was determined by isocratic high-performance liquid chromatography and fluorescence detection. Mean (+/- S.D.) lymphocyte kynureninase activity in a group (n = 12) of vitamin B6-deficient men was 5.04 +/- 0.81 pmol 3 hydroxyanthranilic acid formed per mg protein per min, which was significantly (p = 0.005) lower than the 6.69 +/- 1.70 pmol 3-hydroxyanthranilic acid formed per mg protein per min in men with a normal vitamin B6 status. This indicates that lymphocyte kynureninase activity is depressed during a vitamin B6 deficiency. PMID- 1939452 TI - Random decarboxylation of uroporphyrinogen III by human hepatic uroporphyrinogen decarboxylase. AB - The type III heptacarboxylic porphyrinogens derived from enzymic decarboxylation of an acetic acid substituent on uroporphyrinogen III to a methyl group by human hepatic uroporphyrinogen decarboxylase has been analysed by reversed-phase high performance liquid chromatography with electrochemical detection. The results showed that all four possible heptacarboxylic acid porphyrinogen isomers, with the methyl group attached to rings A, B, C and D of the tetrapyrrole macrocycle, respectively, were formed in almost equal proportions. It was concluded that the normal pathway of uroporphyrinogen III decarboxylation in human liver follows a random mechanism. PMID- 1939451 TI - High-performance liquid chromatographic assays for protoporphyrinogen oxidase and ferrochelatase in human leucocytes. AB - Rapid, sensitive and specific high-performance liquid chromatographic assays are described for protoporphyrinogen oxidase and ferrochelatase in human leucocytes. The enzyme reaction products were separated and quantitated by reversed-phase high-performance liquid chromatography with fluorescence detection. The optimal pH for the protoporphyrinogen oxidase assay was 8.6 and the Michaelis constant for protoporphyrinogen IX was 9.78 +/- 0.96 microM (mean +/- S.D.). The mean (+/- S.D.) activity of protoporphyrinogen oxidase in fourteen apparently healthy subjects was 0.146 +/- 0.023 nmol protoporphyrin IX per min per mg protein. In one patient with variegate porphyria, the activity was 0.028 nmol protoporphyrin IX per min per mg protein. The optimal pH for ferrochelatase was 7.4 and with protoporphyrin and Zn2+ as substrates, the Michaelis constants were 1.49 and 8.33 microM, respectively. The mean activity of ferrochelatase in ten control subjects was 0.24 nM Zn-protoporphyrin or 2.05 nM Zn-mesoporphyrin formed per h per mg protein. PMID- 1939453 TI - Determination of 125I-labelled thyroxine glucuronide by reversed-phase high performance liquid chromatography using on-line radiochemical detection to determine UDPglucuronosyltransferase activity. AB - A convenient, fast and highly sensitive high-performance liquid chromatographic method, using on-line radiochemical detection, is described for the determination of [125I]thyroxine glucuronide. The method involves direct injection of the supernatant, a total analysis time of 30 min and a detection limit of 1 pmol. The results demonstrate that the method is suitable for the determination of UDPglucuronosyltransferase activity with thyroxine as substrate in native hepatic microsomes. The rate of thyroxine glucuronidation in microsomes from rats treated with Arodor 1254 was ten times higher than in control microsomes, indicating that with this method, increases of UDPglucuronosyltransferase thyroxine activities, often associated with hepatic induction process involved in thyroid hypertrophy, can be easily detected. This method could also be applied to all experimental biological systems that involve the separation and quantification of [125I]thyroxine and [125I]thyroxine glucuronide. PMID- 1939454 TI - Use of anion-exchange high-performance liquid chromatography for the study of smooth muscle myosin light-chain kinase and its catalytic domain. AB - Avian myosin light-chain kinase from smooth muscle of the gizzard and its catalytic domain, derived from the intact enzyme by trypsin digestion, was purified within 30-40 min by both analytical and preparative anion-exchange high performance liquid chromatography. The proteins obtained were more than 95% pure and retained their biological activity. The high-performance anion-exchange chromatography protocols represent a significant decrease in purification time when compared with conventional ion-exchange chromatography. PMID- 1939455 TI - Radio-detection high-performance liquid chromatographic enzyme assay for inhibitors of fungal sterol delta 14-reductase. AB - An enzyme assay for inhibitors of fungal sterol delta 14-reductase employing isocratic reversed-phase high-performance liquid chromatography is described. A Hypersil 5-microns octadecylsilyl (ODS) column (250 mm x 4.6 mm I.D.) was used and a mobile phase consisting of methanol-water-ethanol (86:4:10, v/v) was pumped at a flow-rate of 1.5 ml/min. Typical analysis times were 15 min. Using [4 14C]ignosterol as a substrate and an enzyme preparation from Saccharomyces cerevisiae, this method was used to compare the inhibition of sterol delta 14 reductase by the fungicides fenpropidin and fenpropimorph with three N substituted 8-azadecaline compounds. PMID- 1939456 TI - p-nitrophenyllaurate: a substrate for the high-performance liquid chromatographic determination of lipase activity. AB - Many assay procedures have been devised to measure lipolytic activity, but none is without problems. It is for this reason that new methods are still being proposed. In this work we have investigated the use of two esters of p nitrophenol, the palmitic acid and lauric acid esters, as substrates for a highly sensitive high-performance liquid chromatographic method. Data on recovery, specific activity and reproducibility are reported only for the lauric ester, because the palmitic ester turned out to be a very poor substrate. PMID- 1939457 TI - High-performance liquid chromatographic investigation of product formation in the horseradish peroxidase-enhanced chemiluminescence of luminol with different enhancers. AB - A reversed-phase high-performance liquid chromatographic method for the investigation of the chemiluminescence-producing oxidation of luminol by the enzyme horseradish peroxidase is presented. Both the kinetics and the mechanism of product formation can be monitored. Special attention is paid to the mechanism of enhancement of the chemiluminescence by phenolic compounds, such as p iodophenol, p-hydroxycinnamic acid and 6-hydroxybenzothiazole. The function of the enhancers was elucidated partially by the observation of a higher degradation rate of luminol. In addition, it was concluded that the mechanism of enhancement is probably different for the various enhancers, based on the product formation. PMID- 1939458 TI - Determination of proteolytic hydrolysis of thyroglobulin. AB - A method for the determination of the free thyronine- and tyrosine-like amino acids in the thyroidal protein thyroglobulin is presented. The compounds of interest are monoiodotyrosine, diiodotyrosine, thyronine, diiodothyronine, triiodothyronine and tetraiodothyronine. The extent of proteolysis was followed by high-performance liquid chromatographic monitoring of both the remaining peptides and the formation of the free thyroidal amino acids. Total hydrolysis was achieved by a combination of proteolytic enzymes. A number of enzymes were tested, such as trypsin, chymotrypsin, pronase, aminopeptidase-M, carboxypeptidase-A, carboxypeptidase-P and carboxypeptidase-Y. The best combination turned out to be pronase followed by aminopeptidase-M. The relative amounts of the enzymes, with respect to the substrate thyroglobulin, and the time of incubation were optimized to achieve total proteolysis in 4 h. The method was applied successfully to samples from a toxicological experiment with sodium bromide. PMID- 1939460 TI - Determination of biocatalyst consumption in an aminopeptidase process using automated sample preparation and high-performance liquid chromatography. AB - A rapid and sensitive method has been developed for the determination of the biocatalyst consumption in the chemo-enzymic production of optically pure natural and synthetic alpha-H-amino acids. It is based on automated sample preparation from an enzymic reaction mixture, reversed-phase high-performance liquid chromatographic separation, post-column reaction and fluorimetric detection. The assay procedure has been applied to the enzymic conversion of racemic norvaline amide into L-norvaline, catalysed by an L-specific aminopeptidase from Pseudomonas putida. Both norvaline amide and norvaline can be analysed in a single assay in the low nanogram range. The method yields reproducible results and requires 30 min from the time of sampling the enzymic reaction mixture to quantitation. The reaction mixture is automatically sampled and analysed several times during the course of the reaction. With the results obtained a conversion curve can be constructed from which the exact biocatalyst consumption can be calculated. By adaptation of the mobile phase, the method can also be applied to other amino acid amides used as substrates in the aminopeptidase reaction. PMID- 1939461 TI - Behaviour studies of the fungicide cymoxanil in two strains of the fungus Botrytis cinerea and in haemolymph of locust and lobster. I. In situ monitoring by internal surface reversed-phase high-performance liquid chromatography. AB - A method for following the metabolism of the fungicide cymoxanil in various biological media is described. By using a recently developed high-performance liquid chromatographic method, with an internal surface reversed-phase column, it is unnecessary to clean up the sample before analysis. Thus this technique makes monitoring in fungi as well as in arthropod haemolymph easier and faster. PMID- 1939459 TI - 5-Methylcytosine content of DNA in blood, synovial mononuclear cells and synovial tissue from patients affected by autoimmune rheumatic diseases. AB - The percentage of 5-methylcytosine (m5Cyt) has been determined in peripheral blood, synovial mononuclear cells and synovial tissue from patients affected by various rheumatic autoimmune diseases. The determination was performed by reversed-phase high-performance liquid chromatography. Fifteen controls were compared to twenty-one patients affected by rheumatoid arthritis and to nine patients affected by systemic lupus erythematosus. The mean percentage of m5Cyt in normal individuals was significantly higher than in the rheumatoid arthritis and systemic lupus erythematosus patients. In addition, patients with active disease showed lower values than patients in remission. This finding is in agreement with the hypothesis that DNA hypomethylation may play a role in the pathogenesis of the autoimmune diseases, resulting in altered oncogene expression. Therapy with cyclosporin A led to a decrease in the percentage of m5Cyt in three rheumatoid arthritis patients, but a rebound was observed when the cyclosporin A was suspended. The percentage of m5Cyt in the DNA of synovial tissue from four rheumatoid arthritis patients and five patients with osteoarthritis was similar; this observation confirms that, in addition to disease-specific and disease activity-specific variations, the percentage of m5Cyt may also show tissue-specific variations. PMID- 1939462 TI - Direct in vitro and in vivo monitoring of destruxins metabolism in insects using internal surface reversed-phase high-performance liquid chromatography. I. Behaviour of E destruxin in locusts. AB - High-performance liquid chromatography with internal surface reversed-phase packing provides an analytical tool for studying the in vitro and in vivo metabolism of A and E destruxins in the haemolymph and various organs of male adults of Locusta migratoria. A slight amount of injected E destruxin is shown to be hydrated into E-diol destruxin in the haemolymph. The rest of the toxin is recovered unchanged in the fat-body, pericardial tissues and Malpighian tubules, and some further E-diol destruxin formation occurs in these organs. Because E diol destruxin is only weakly toxic, this appears to be a detoxication process. PMID- 1939463 TI - Gas chromatographic-mass spectrometric assay to measure urinary N tau methylhistamine excretion in man. AB - An assay has been developed for N tau-methylhistamine, a major metabolite of the autocoid histamine, based on gas chromatography-electron-capture negative-ion chemical ionisation mass spectrometry. N tau-Methylhistamine was extracted from urine by cation-exchange chromatography and converted to its di-(3,5 bistrifluoromethylbenzoyl) derivative. The latter has good chromatographic properties and gives a negative-ion mass spectrum with the molecular ion (M., m/z 605) as base peak. A commercially available trideuterated analogue of N tau methylhistamine was used as internal standard. Basal urinary excretion of N tau methylhistamine in five normal subjects was found to be 0.21 +/- 0.05 mumol/h (289 +/- 74 mumol/mol of creatinine). This value was not significantly altered in these subjects following the infusion of a subpharmacological dose of histamine. In eight atopic volunteers, basal urinary excretion of N tau-methylhistamine was also not significantly changed following challenge with inhaled allergen. PMID- 1939464 TI - Determination of estradiol 2- and 4-hydroxylase activities by gas chromatography with electron-capture detection. AB - A highly sensitive assay has been developed for measuring the rate of formation of 2-hydroxyestradiol and 4-hydroxyestradiol from estradiol by microsomal preparations. Catechol estrogens were converted to heptafluorobutyryl esters, which were separated by capillary column gas chromatography and quantified using electron-capture detection. 2-Hydroxyestradiol 17-acetate was used as an internal standard. The identity of catechol estrogen derivatives was verified by gas chromatography-mass spectrometry using negative-ion chemical ionization. Estrogens were identified by negative molecular ions and/or by characteristic fragments. This procedure permits quantification of catechol estrogens at the subpicogram level. The assay was validated by comparing estrogen 2- and 4 hydroxylase activities in microsomes from hamster and rat liver with values reported previously. PMID- 1939465 TI - Separation and determination of saturated very-long-chain free fatty acids in plasma of patients with adrenoleukodystrophy using solid-phase extraction and high-performance liquid chromatographic analysis. AB - An improved method was developed for the isolation of very-long-chain free fatty acids (VLCFFAs) in plasma and their separation and determination by high performance liquid chromatography (HPLC). The method includes sample clean-up using solid-phase extraction, fluorophoric labelling of the FFAs and reversed phase HPLC separation. The solid-phase extraction was carried out with aminopropyl-bonded phase columns. The FFAs were then derivatized with 9 anthryldiazomethane (fluorescent) reagent and separated by HPLC on an RP-18 column with methanol as the mobile phase. Using this method, the concentrations of C20:0, C22:0, C24:0 and C26:0 were determined in the plasma of five adrenoleukodystrophy (ALD) patients, one obligatory heterozygote, four healthy male volunteers and one child with cerebral leukodystrophy but without any other ALD symptoms. Statistically significant differences were found in the levels of C24 and C26 and in the ratios C24/C22 and C26/C22 in ALD patients and in normal controls. The values were higher in patients with X-ALD. This method therefore provides a rapid and accurate procedure for the laboratory confirmation of X-ALD. PMID- 1939466 TI - Determination of urinary vanillactic acid and plasma dihydroxyphenylalanine as markers of non-secreting neuroblastoma by high-performance liquid chromatography with electrochemical detection. AB - An accurate and precise isocratic high-performance liquid chromatographic technique for the analysis of urinary vanillactic acid (VLA) and plasma dihydroxyphenylalanine (DOPA), especially at low concentrations (pmol/l) for VLA and nmol/l for DOPA), is described. The compounds were purified in a single step, (on an anion exchanger for VLA and on aluminium oxide for DOPA), separated by ion pair reversed-phase liquid chromatography, and detected electrochemically. A single analysis was complete within 18 min. Mean recoveries of 103 and 81% were obtained for VLA and DOPA, respectively, and the limits of detection were 42 and 76 pmol/l, respectively. The mean values of the intra-assay coefficient of variation were 14 and 7.1% for VLA and DOPA, respectively, and the mean values of the inter-assay coefficient of variation were 15.7 and 11.6%, respectively. Modifications of the retention times (between 2 and 42 min) induced by changes in the eluent were determined. Reference values for normal children and children with neuroblastoma or various tumours are given. PMID- 1939467 TI - Studies on steroids. CCLII. Separation and characterization of 3-oxobile acids in serum by high-performance liquid chromatography with fluorescence detection. AB - The separation of unconjugated and glycine- and taurine-conjugated bile acids with a C-3 oxo group has been carried out by high-performance liquid chromatography on a reversed-phase column. The chromatographic behaviour of these 3-oxobile acids was dependent on the number and positions of hydroxyl groups and the structure of the side-chain. The newly developed method has been applied to the characterization of 3-oxobile acids in biological fluids. The bile acid fraction was obtained from a serum specimen by passing it through a Sep-Pak C18 cartridge. 3-Oxobile acids were derivatized quantitatively to fluorescent oximes through the oxo group by treatment with O-(2-anthrylmethyl)hydroxylamine. The derivatives were separated into the unconjugated and glycine- and taurine conjugated fractions by ion-exchange chromatography on a lipophilic gel, piperidinohydroxypropyl Sephadex LH-20. Subsequent resolution of each fraction into individual 3-oxobile acids was achieved by chromatography on a Nova-Pak Phenyl column using 3% methanol in 0.3% potassium phosphate buffer (pH 7.0) acetonitrile (8:5, v/v) as the mobile phase. The derivatized 3-oxobile acids were monitored by fluorescence detection (excitation wavelength 260 nm and emission wavelength 405 nm), the limit of detection being 20 fmol. Glycine- and taurine conjugated 7 alpha,12 alpha-dihydroxy- and 7 alpha-hydroxy-3-oxo-5 beta-cholanoic acids in human serum were unambiguously idenitified on the basis of their chromatographic behaviour using mobile phases of different pH values. PMID- 1939468 TI - Analysis of plasma catecholamines by high-performance liquid chromatography with fluorescence detection: simple sample preparation for pre-column fluorescence derivatization. AB - Analysis of plasma catecholamines (norepinephrine, epinephrine and dopamine) by high-performance liquid chromatography using 1,2-diphenylethylenediamine as a fluorescent reagent is described. We have developed an automatic catecholamine analyser, based on pre-column fluorescence derivatization and column switching. The analysis time for one assay was 15 min. The correlation coefficients of the linear regression equations were greater than 0.9996 in the range 10-10,000 pg/ml. The detection limit, at a signal-to-noise ratio of 3, was 2 pg/ml for dopamine. A new method of sample preparation for the pre-column fluorescence derivatization of plasma catecholamines was used. In order to protect the catecholamines from decomposition, an ion-pair complex between boric acid and the diol group in the catecholamine was formed at a weakly alkaline pH. The stabilities of plasma catecholamines were evaluated at several temperatures. After complex formation, the catecholamines were very stable at 17 degrees C for 8 h, and the coefficients of variation for norepinephrine, epinephrine and dopamine were 1.2, 4.2 and 9.3%, respectively. PMID- 1939469 TI - Quantities of adult, fetal and embryonic globin chains in the blood of eighteen- to twenty-week-old human fetuses. AB - The prenatal diagnostic program, established at Hacettepe University in Ankara for the purpose of detecting beta-thalassemia (beta-thal), sickle cell anemia (SS), and Hb S-beta-thal, offered the opportunity of evaluating the relative quantities of adult (beta A, beta S), fetal (G gamma, A gamma, A gamma T), and embryonic (epsilon, zeta) chains in 26 fetuses, aged 18-20 weeks. Methodology involved micro high-performance liquid chromatographic (HPLC) procedures and immunology using an mAb, specific for the embryonic epsilon chain. A good correlation was observed between the beta/gamma in vitro chain synthesis ratio and the level of beta A and/or beta S chains determined by reversed-phase HPLC; the combination of these two sets of data strengthens the prenatal diagnostic approach of detecting beta-thal major but not beta-thal trait. The levels of the different gamma chains were about as observed in newborn babies; the frequency of the A gamma T variant in the 26 fetuses was the same as observed for a larger group of Turkish newborn babies. The level of the embryonic zeta chain was higher than seen in full-term babies and varied between 0 and 1.3%; 5 of the 26 fetuses showed the complete absence of zeta. The embryonic epsilon chain was not detectable, not even in babies with beta-thal major. These data indicate that the synthesis of epsilon is completely turned off in fetuses at the age of 18-20 weeks, while that of zeta continues, albeit at a low level. PMID- 1939470 TI - Assay of human transthyretin-bound holo-retinol-binding protein with reversed phase high-performance liquid chromatography. AB - We describe a reversed-phase high-performance liquid chromatographic method for the determination of vitamin A-transporting (holo) transthyretin-bound (TTR) retinol-binding protein (RBP) concentrations in serum or plasma. Holo-TTR-RBP and free retinol derived primarily from free RBP are consistently observed with this chromatographic method. Holo-TTR-RBP concentrations determined by this method are highly correlated to holo-TTR-RBP concentrations measured by chromatography. This method has the advantage of using less expensive columns and having peak areas which are more proportional to their true concentrations in plasma, as determined by comparison to purified protein spectrophotometry and radial immunodiffusion. The percentage of RBP circulating as holo-TTR-RBP decreased significantly as the total concentration of RBP or retinol increased. Because purified holo-TTR-RBP did not dissociate under these chromatographic conditions, this suggests that more vitamin A circulates as holo-free RBP or free retinol in the blood of people with high serum RBP. PMID- 1939471 TI - High-performance liquid chromatographic procedure for the simultaneous determination of aromatic L-amino acid decarboxylase activity towards 3,4 dihydroxyphenylalanine and 5-hydroxytryptophan. AB - A high-performance liquid chromatographic method with electrochemical detection has been developed and applied in the simultaneous determination of aromatic L amino acid decarboxylase activity with respect to L-3,4-dihydroxyphenylalanine and 5-hydroxytryptophan as substrates. Both substrates are included in the incubation mixture, and the decarboxylated products, dopamine and serotonin, respectively, are detected. In contrast to several earlier claims, we found that the ratio of the decarboxylase activity to L-3,4-dihydroxyphenylalanine and 5 hydroxytryptophan is quite constant across several different rat tissues, supporting the notion that there is only one major single enzyme rather than two. We also observed that an erroneous ratio with respect to the L-3,4 dihydroxyphenylalanine/5-hydroxytryptophan decarboxylation activities, is obtained if these activities are assessed under non-linear kinetic conditions. PMID- 1939472 TI - Development of analytical methods for some penicillins in bovine milk by ion paired chromatography and confirmation by thermospray mass spectrometry. AB - Analytical methods for the determination of cloxacillin, ampicillin/hetacillin, and amoxicillin in bovine milk were developed. The methods involved ultrafiltration of milk diluted with methanol, acetonitrile, and water on a 10,000-dalton cut-off filter. Separation of penicillins from other milk components was accomplished by ion-paired chromatography using a microbore column. The penicillins were detected using ultraviolet photodiode array (UV-PDA) detection and confirmed by thermospray liquid chromatography-mass spectrometry (LC-MS). The thermospray spectra of these compounds exhibited [M + H]+ and [M + Na]+ ions along with several fragment ions. The limits of detection for these antibiotics were estimated to be 50 to 100 ppb for LC with UV-PDA detection and 100-200 ppb for thermospray LC-MS detection. PMID- 1939474 TI - Determination of diclofenac and its metabolites in plasma and cerebrospinal fluid by high-performance liquid chromatography with electrochemical detection. AB - A reversed-phase high-performance liquid chromatographic method with electrochemical detection for the quantitation of diclofenac and metabolites in plasma and cerebrospinal fluid has been developed. Pirprofen is employed as internal standard. Samples are extracted with C18 solid-phase extraction columns and eluted with methanol. Oxidation potentials for detection were established by constructing voltammograms for each compound. In the concentration range found in human studies, the intra-day coefficients of variation were always less than 6%. The procedure allows the simultaneous determination of diclofenac and its four major metabolites with very low detection limits (less than 1 ng/ml), which were sufficient even for kinetic studies in cerebrospinal fluid. PMID- 1939473 TI - Simple and accurate determination of methylpyrazines in biofluids using high performance liquid chromatography. AB - The determination of six methylpyrazines was performed using high-performance liquid chromatography (HPLC). Methylpyrazines were simultaneously extracted and injected onto a silica gel column with a syringe-type minicolumn packed with diatomaceous earth granules. The extraction-injection solvent used was dichloromethane and the mobile phase solvent for HPLC was dichloromethane containing 0.08% of 1.65 M ammonia solution and 0.5% of methanol. Methylpyrazines were detected using an ultraviolet detector set at 275 nm. Linear relationships between the amount of sample and peak height were confirmed from 50 ng/ml to 10 micrograms/ml of the biofluids. When an aliquot of 10 microliters of biofluid was introduced to the minicolumn, the detection limit of methylpyrazines was as low as 30 ng/ml with each pyrazine derivative. The method is simple and accurate and is thus applicable to pharmacokinetic studies which are performed on animals. The results showed that the possible pharmacological effects of methylpyrazines might be evaluated pharmacokinetically using this newly developed technique. PMID- 1939475 TI - High-performance liquid chromatographic assay with ultraviolet detection for the determination of etoperidone and two active metabolites, 5-(1-hydroxyethyl) etoperidone and 1-(3-chlorophenyl)piperazine, in plasma. AB - A selective and sensitive high-performance liquid chromatographic assay with ultraviolet detection for the determination of the antidepressant drug etoperidone and two active metabolites in plasma is described. The drug, metabolites and internal standard are isolated from plasma using a two-step liquid-liquid extraction procedure. The resulting sample is chromatographed on a C18 column (10 cm x 2.1 mm I.D.) with ultraviolet detection at 254 nm. Standard curves are linear for each compound over the concentration range 2-1000 ng/ml. The accuracy and precision of the assay, expressed as the percentage deviation of measured values from the true value and the relative standard deviation (inter run), are less than or equal to 10% at all concentrations except the minimum quantification limit. Using an automated injector and computerized data acquisition, eighty samples can be routinely processed in one day. The assay has been successfully used for the analysis of plasma samples from pharmacokinetic studies in mice, rats, dogs and humans. PMID- 1939476 TI - Sensitive one-step extraction procedure for column liquid chromatographic determination of fluvoxamine in human and rat plasma. AB - A normal-phase column liquid chromatographic assay for fluvoxamine, a recently introduced atypical antidepressant, has been developed. Prior to analysis, aliquots of alkalinized plasma were extracted with n-hexane. These extracts were then injected into a 5-microns Resolve spherical silica column. Fluvoxamine and the internal standard, clovoxamine, were detected at a wavelength of 254 nm. Standard curves were linear over the concentration range 2-400 ng/ml. Acceptable coefficients of variation were obtained for both within-run and day-to-day studies. The estimated limit of detection is 0.5 ng/ml, and selected drugs checked for coadministration show no analytical interference. This assay was used to evaluate the pharmacokinetics of fluvoxamine in rats. PMID- 1939477 TI - High-performance liquid chromatographic assay for amiloride in plasma and urine. AB - A sensitive and simplified high-performance liquid chromatographic procedure has been developed for quantification of amiloride in rabbit plasma, as well as human plasma and urine. Following protein precipitation with perchloric acid, the supernatant was directly injected into a C18 Nucleosil column. The mobile phase consisted of methanol-water (45:55) containing 0.1 M perchloric acid, and the compound was quantitated using a fluorescence detector at excitation and emission wavelengths of 286 and 418 nm, respectively. The average recovery was 97.6%. The calibration curve was linear over the range 2.0-20.0 ng/ml. The limit of detection was 0.5 ng/ml. PMID- 1939478 TI - High-performance liquid chromatographic determination of histamine N methyltransferase activity. AB - A method for the determination of histamine N-methyltransferase (HMT) activity by high-performance liquid chromatography based on post-column derivatization with omicron-phthalaldehyde is described. The determination involves the separation of the substrate, histamine, from its product. N tau-methylhistamine, using a weak cation exchanger, followed by on-line derivatization of these imidazoleamines with omicron-phthalaldehyde and their detection and quantitation with a fluorimetric detector. This assay method is suitable for the measurement of HMT activity during enzyme purification. PMID- 1939479 TI - Determination of a new blood glucose-lowering agent in biological fluids by capillary gas chromatography using electron-capture detection. AB - A gas chromatographic method for the determination of 5-(4-chlorophenyl)-2-[(4 methylphenyl)sulphonyl]-4-pentynoic acid (I) in plasma (serum) and urine has been developed. After an extraction process, the cleaned-up organic extract was derivatized with diazomethane at ambient temperature. Results are evaluated from peak-height ratios with respect to the appropriate internal standard. The detection limit following extraction of a 1-ml plasma sample is about 20 ng/ml. PMID- 1939480 TI - High-performance liquid chromatographic method for the simultaneous determination of R-(-)- and S-(+)-hexobarbital in rat plasma. AB - The enantiospecific determination of R- and S-hexobarbital in rat plasma is described. The method involves liquid-liquid extraction of racemic hexobarbital from plasma, separation of the underivatized enantiomers by high-performance liquid chromatography on an alpha 1-acid glycoprotein column and ultraviolet detection. The mobile phase consists of a phosphate buffer (pH 5.4) containing 0.4% 2-propanol as organic modifier. An alpha 1-acid glycoprotein guard column is used to increase the lifetime of the analytical column. Heptabarbital is the achiral internal standard. With detection limits of ca. 0.05 microgram/ml for both R- and S-hexobarbital, the assay is suitable for pharmacokinetic studies of the enantiomers in rats. PMID- 1939481 TI - Determination of naltrexone and 6 beta-naltrexol in plasma by high-performance liquid chromatography with coulometric detection. AB - A simple and reliable reversed-phase high-performance liquid chromatographic method with coulometric detection is described for the quantitation of naltrexone and its metabolite, 6 beta-naltrexol, in plasma samples of healthy volunteers who received orally 50 mg of naltrexone. The analytes and the internal standard, naloxone, are extracted with an octadecyl solid-phase extraction column before chromatography. The mobile phase is 0.01 M potassium phosphate (pH 3) acetonitrile (85:15, v/v) and it is pumped at 0.8 ml/min. The coulometric detector is formed by two electrodes set at +0.20 V and +0.70 V, with a palladium reference electrode. The limit of quantitation observed was 5 ng/ml for both naltrexone and 6 beta-naltrexol. This method can be used to investigate pharmacokinetic parameters of different pharmaceutical preparations of this opioid antagonist. PMID- 1939482 TI - Method for separation and determination of lactone and hydroxy acid forms of a new HMG CoA reductase inhibitor (RG 12561) in plasma. AB - The new drug RG 12561 (I) is a lactone that is undergoing clinical evaluation for its cholesterol lowering effect based on potent HMG CoA reductase inhibitory activity displayed by its open hydroxy acid form. To determine the dispositional characteristics of the drug, a method was developed for determination of the two forms in plasma. A 0.25-ml aliquot of plasma was deproteinized with 0.5 ml of methanol, and the lactone was extracted with hexane-ethyl acetate (75:25, v/v). The methanolic plasma was then acidified followed by extraction of the hydroxy acid with hexane-ethyl acetate. The extracts were dried, reconstituted and analyzed by isocratic, reversed-phase high-performance liquid chromatography using ultraviolet absorbance at 254 nm. The separations were performed utilizing a C18 column with mobile phase consisting of acetonitrile, 2-propanol and 0.1 M acetate buffer (pH 5), the proportions of which differed depending on the form of drug analyzed. The method was found to be selective and a quantitation limit of 50 ng/ml was established. Validation studies demonstrated that the method was sufficiently accurate and precise for determining disposition of the drug in the dog. PMID- 1939483 TI - Detection and determination of free and plasma protein-bound astemizole by thin layer chromatography: a useful technique for bioavailability studies. AB - A thin-layer chromatographic (TLC) procedure has been developed for the determination of astemizole in plasma as the free and as protein-bound substance. The detection and quantification were performed without using internal standards. In earlier described methods for the estimation of astemizole by high-performance liquid chromatography and radioimmunoassay, only free levels in plasma were quantified, at 3.3% of the total astemizole, with the remaining 96.7% bound to plasma protein and tissue. Our method employs proteolysis of plasma proteins by incubating plasma for 2 h in pepsin. After proteolysis the astemizole is extracted, and a known amount of the extract is spotted on precoated silica gel F 254 plates. Astemizole was quantified using a Shimadzu CS-930 dual-wavelength TLC scanner. The method provides a direct estimate of total astemizole present in the plasma. PMID- 1939485 TI - Biomedical applications of electrophoretic techniques. PMID- 1939484 TI - New assay method for the determination of vinpocetine in human plasma by gas chromatography-mass spectrometry without transesterification caused by solvents: a reply. PMID- 1939486 TI - Application of capillary isotachophoresis in peptide analysis. AB - This paper gives a broad and detailed review of the applications of one of the modern high-performance electromigration separation techniques--capillary isotachophoresis (ITP)--in peptide analysis. Examples are presented of the utilization of capillary ITP for peptide analysis in the fields of chemistry, general and clinical biochemistry, biology, biotechnology, pharmacy and the food industry. The complete composition of all the electrolyte systems used for peptide ITP analyses in both cationic and anionic techniques is given in tabular form. According to the purpose of analysis the applications are divided into several sections: model studies, determination of physico-chemical characteristics, purity control of both intermediate and final peptide preparations, including the determination of low-molecular-mass ionogenic admixtures, and the analysis of peptides in biological fluids and tissue extracts. In addition to the main applications the theoretical and methodological aspects of peptide ITP analysis are discussed. The basic electromigration properties of peptides (their polyampholyte character, effective and absolute mobilities, acid-base equilibria) are explained and the selection of parameters for peptide ITP analysis is described in detail. The advantages and disadvantages of ITP compared with other electrophoretic and chromatographic methods used for peptide analysis are discussed. PMID- 1939487 TI - Isoelectric focusing in immobilized pH gradients: applications in clinical chemistry and forensic analysis. AB - The applications of isoelectric focusing in immobilized pH gradients in clinical chemistry and forensic analysis are reviewed. Strong emphasis is given to the separation of serum proteins, in particular alpha 1-acidic glycoprotein, acid phosphatase, alkaline phosphatase, alpha 1-antitrypsin, apolipoproteins, complement component, factor B, factor XIIIB, group-specific component, lecithin:cholesterol acyltransferase, phosphoglucomutase, prealbumin, protein C and transferrin. The analysis of human parotid salivary proteins is discussed and an assessment is given of the state of the art in thalassaemia screening. PMID- 1939488 TI - Sodium dodecyl sulphate electrophoresis of urinary proteins. AB - The analysis of urinary proteins and their identification are discussed, particularly in regard to the technique of sodium dodecyl sulphate electrophoresis in polyacrylamide gradient gels. Urine collection, storage and preparation are evaluated, especially in regard to problems connected with concentration and dialysis of such samples. The instrumental approach to sodium dodecyl sulphate polyacrylamide gel electrophoresis represented by the Phast System appears to be particularly valuable in routine clinical analysis of urine specimens, since no sample pretreatment is required. The following types of proteinurias are evaluated: (a) orthostatic proteinurias; (b) post-renal proteinurias; (c) Bence-Jones proteinuria; (d) lower and upper urinary tract infection (cystitis and pyelonephritis) and (e) diabetes mellitus proteinurias. PMID- 1939489 TI - Clinical applications of electrophoresis of human salivary proteins. AB - Human salivary proteins have been studied by electrophoresis in denaturing and non-denaturing polyacrylamide gel electrophoresis (PAGE) as well as by isoelectric focusing (IEF) and two-dimensional procedures, and the clinical applications of this have been reviewed. Whilst non-denaturing PAGE is useful in studying polymorphisms, sodium dodecylsulphate PAGE appears to be otherwise preferable. Immobilized pH gradients containing carrier ampholytes (CAs) give better resolution than CA-based IEF and overcome the problems of cathode drift and loss of basic material. Proline-rich proteins stain poorly with conventional procedures and special techniques are necessary. In clinical studies, findings must be viewed over and above the large number of polymorphisms which occur normally. Studies relating salivary protein and peptide profiles to dental caries susceptibility are encouraging. Specific protein abnormalities have been associated with connective tissue disorders and could form the basis of new non invasive diagnostic procedures. Protein differences associated with cystic fibrosis and diabetes mellitus, however, merit reinvestigation with the new procedures now available. Detection of HIV antigens in saliva is a new area of research. In the light of new techniques available and new information which has arisen from DNA studies, future prospects for the clinical applications of electrophoresis of saliva look good. PMID- 1939490 TI - Analysis of cerebrospinal fluid proteins by electrophoresis. AB - The cerebrospinal fluid (CSF) is a specific ultrafiltrate of plasma, which surrounds the brain and spinal cord. The study of its proteins and their alteration may yield useful information on several neurological diseases. By using various electrophoretic separation techniques, several CSF proteins have been identified derived from plasma or from brain. Different one-dimensional methods, such as agarose gel electrophoresis and isoelectric focusing, are of similar value in identifying the non-specific oligoclonal bands, which are mainly helpful in the diagnosis of multiple sclerosis and other inflammatory diseases. Isoelectric focusing has a greater resolution than other one-dimensional methods, and it yields additional data about disease-associated proteins occurring in Alzheimer's disease, Huntington's chorea and amyotrophic lateral sclerosis. Silver-stained two-dimensional gels provide more information about the complex protein composition of CSF, particularly about proteins produced in the brain, such as apolipoprotein E and neuron-specific enolase. For the detection of oligoclonal antibodies, the investigation of protein changes revealed by Parkinson's disease, schizophrenia and Creutzfeldt-Jakob disease, and the analysis of CSF immune complexes, two-dimensional electrophoresis has a greater sensitivity. PMID- 1939491 TI - Theoretical background for clinical and biomedical applications of electromigration techniques. AB - This review presents the theoretical principles of analytical electrophoresis. The basic rules which control the movement of ionic species in electrostatic fields, together with the phenomenological theory of the resulting mass transport are analysed. The separation principles and capabilities of zone electrophoresis, isotachophoresis, isoelectric focusing, micellar electrokinetic chromatography and gel electrophoresis are evaluated. The most important effects accompanying electrophoresis, such as the production of Joule heat, electroosmosis and diffusion are discussed. PMID- 1939492 TI - Electrophoresis of serum isoenzymes and proteins following acute myocardial infarction. AB - The clinical significance of the serum enzymes creatine kinase (CK, EC 2.7.3.2), lactate dehydrogenase (LD, EC 1.1.1.27) and aspartate aminotransferase (EC 2.6.1.1), and the isoenzymes CK 1-3 and LD 1-5, in acute myocardial infarction (AMI) is reviewed. Particular attention is given to electrophoretic analysis of the isoenzymes (and the CK isoforms/subforms) following AMI and thrombolytic therapy. Other protein markers for the monitoring of AMI, including myoglobin and muscle contractile proteins, are also discussed and the potential for the detection of new marker proteins using high-resolution two-dimensional electrophoretic methods is demonstrated. Whilst emphasis is placed upon electrophoretic methods the value of complementary immunoassays is acknowledged in order to maintain a balanced perspective. PMID- 1939493 TI - Electrophoretic analysis of enzyme-linked immunoglobulins and their clinical significance. AB - The appearance of circulating enzyme-linked immunoglobulin complexes (E-Ig) is common for most enzymes used in clinical biochemical tests. The presence of E-Ig may result in altered enzyme activity in serum and interfere with the measurement of isoenzymes, and is thus of diagnostic importance. E-Ig can be identified by confirming that the binding protein is an immunoglobulin by its reaction with specific anti-human immunoglobulin antibodies. Currently, the presence of E-Ig in an individual is regarded as a benign phenomenon, not indicative of any particular disease process. However, it is becoming clear that E-IgG are closely associated with autoimmune states. PMID- 1939494 TI - Utility of protein electrophoretic analysis in the characterization of malignant tissues. AB - High-resolution electrophoresis of samples from malignant tissues and tumour cells has developed from a simple analytical tool to a high-tech system requiring a lot of satellite techniques. Though this developmental history now demands additional expensive instrumentation and a detailed knowledge of protein chemistry, the usefulness of this technique in tumour biology has been dramatically enhanced. Consequently, electrophoretic techniques combined with additional high-resolution and sensitive analytical tools can now be used to elucidate a particular phenotype of a cancer cell; moreover, the chemical nature of this phenotype can be revealed. The way from the protein backwards to the gene is now open! PMID- 1939496 TI - Electrophoresis of mutant proteins in inherited diseases. AB - The electrophoretic approaches for detection of mutant proteins in inherited diseases are briefly reviewed and discussed. Mutation of a protein, known to be associated with a specific inherited disease, is detected by immunoblotting, immunoprecipitation or enzyme staining, combined with various electrophoretic techniques. Some instrumental and technological devices for two-dimensional electrophoresis have been reported for the screening of mutant proteins in diseases of currently unknown etiology. PMID- 1939495 TI - Electrophoretic analysis of nuclear matrix proteins and the potential clinical applications. AB - Nuclear matrix proteins form the skeleton of the nucleus and participate in the various cellular functions of the nucleus. These proteins have been demonstrated to be tissue-type specific and can potentially reflect changes in the state of differentiation of the cell. Elucidating nuclear matrix protein changes necessitates the use of high-resolution two-dimensional polyacrylamide gel electrophoresis. Separation of this complex mixture into its component parts resolves protein changes when comparing the normal state to a diseased state of a cell. Evidence has been reviewed which shows the potential use of nuclear matrix proteins and antibodies to nuclear matrix proteins as diagnostic tools for various cancers, autoimmune diseases, adenoviral infection, and other diseases. Consequently, the central functions of the nuclear matrix in the cell allow it to have significant potential as a diagnostic agent. PMID- 1939497 TI - Biomedical relevance of two-dimensional protein mapping. AB - State-of-the-art and future perspectives are discussed for the application of two dimensional protein maps to basic medical research and routine clinical chemistry problems. Despite the technical advances that allow effective processing of a large number of samples and the refinement of devices and procedures for image analysis, at present two-dimensional maps are mostly confined to research purposes, i.e. to the inventory of normal constituents of body fluids and tissues on the one hand, and to qualitative-quantitative alterations of some protein spots in a number of instances (genetic, degenerative, infectious or xenobiotic diseases) on the other. It is hoped that in some instances a single primarily affected component will be able to be identified and then specifically tested (for instance by immunological means) as a diagnostic marker, but complex pathological patterns would still require the analysis of a large number of peptides at the resolution level only afforded by two dimensions. Further simplification of the protocols, for example with ready-made gels, and data reduction systems might then allow the application of the technique to be extended to general clinical laboratories. PMID- 1939498 TI - Capillary zone electrophoresis: its applicability and potential in biochemical analysis. AB - Recent developments in capillary zone electrophoresis (CZE) are reviewed, starting with available instrumentation, a description of different operational modes and the most commonly used detection systems. Appropriate attention is paid to CZE-mass spectrometry coupling and coupling of electrophoretic and chromatographic procedures. The possibility of separating chiral molecules is also discussed. Examples of applications concern mainly amino acids, peptides, proteins, nucleic acids and their constituents. PMID- 1939500 TI - Post-column on-line HPLC measurement of reaction rates by using an open-closed derivatizing system. AB - An open-closed high-performance liquid chromatography (HPLC) assembly that enables post-column derivatization of the eluates and kinetic measurements (reaction-rate methods) with enhanced sensitivity and selectivity is constructed and tested by applying it to the separation and determination of the three main creatine kinase (CK) isoenzymes in serum samples with excellent results (consistent with those provided by the standard method) and recoveries between 95 and 105%. PMID- 1939499 TI - Identification of minor C18 triene and conjugated diene isomers in hydrogenated soybean oil and margarine by GC-MI-FT-IR spectroscopy. AB - Vegetable oils are partially hydrogenated in order to produce palatable products of suitable plasticity. The constituents of these new dietary products are complex mixtures of fatty acid isomers with different nutritional properties. A rapid method is described for separating and identifying fatty acid methyl ester (FAME) isomers of linolenic (octadecatrienoic, 18:3) acid and of conjugated octadecadienoic (18:2) acid, minor species found in hydrogenated soybean oil and margarine, by capillary gas chromatography-matrix isolation-Fourier transform infrared (GC-MI-FT-IR) spectroscopy. FAMEs of 18:3 acid isomers in margarine, soybean oil hydrogenated in our laboratory, and isomerized linolenic acid were identified by this method, and MI-FT-IR spectra of FAME geometric isomers of octadecatrienoic and conjugated octadecadienoic acids are reported for the first time. Five major C18 triene GC peaks are found in chromatograms of isomerized methyl linolenate, representing species with tri-cis and tri-trans configurations and three species with cis-trans mixed configurations. FAME isomers with these configurations are also found for a hydrogenated soybean oil having an iodine value of 111. Methyl linolenate (tri-cis) is no longer found when soybean oil is further hydrogenated to an iodine value of 96. IR spectra characteristic of a tri trans isomer are obtained for two test samples with iodine values of 111 and 96. Besides methyl linolenate, only isomers with a mono-trans di-cis configuration are found for the margarine analyzed. Conjugated cis-trans and trans-trans 18:2 FAME isomers are also found in all the hydrogenated soybean oil and margarine analyzed. PMID- 1939501 TI - Detection of double-stranded RNA by ELISA and dot immunobinding assay using an antiserum to synthetic polynucleotides. AB - An antiserum against polyinosinic-polycytidylic acid (In-Cn) was used to detect double-stranded RNA (dsRNA) by several serological techniques. DsRNA was readily detected by indirect ELISA (ELISA-I) and dot immunobinding assay (DIA). Addition of the antigen to poly-L-lysine-precoated plates and blocking with uncreamed milk powder allowed detection levels of 100 pg.ml-1 In-Cn by ELISA-I. Concentrations as low as 1 ng.ml-1 were detected by DIA using polyvinyliden difluoride (PVDF) membranes. Detection capacity with nitrocellulose membranes was 1000 times lower than with PVDF. ELISA-I and DIA enabled detection of dsRNA in enriched fractions from cucumber mosaic virus (CMV)- and citrus tristeza virus (CTV)-infected plants and from virus-infected Penicillium chrysogenum mycelium. These techniques showed similar or higher sensitivity for detection of dsRNA than separation by polyacrylamide gel electrophoresis and silver staining. PMID- 1939502 TI - An ELISA procedure for the diagnosis of dengue infections. AB - Although the hemagglutination-inhibition (HI) test has been the standard test used by the World Health Organization (WHO) for the classification of serologic response in dengue infections, it is slow, requiring paired specimens. Furthermore, not all investigators have accepted the classification. Thus, there is an urgent need to develop a rapid test which employs a single specimen. We developed an enzyme-linked immunosorbent assay (ELISA) for rapid classification of serologic responses in dengue infections based on the ratio of IgM and IgG in a single specimen. Using the criteria established by the WHO (1986) for comparison, concordant results were obtained in 81% and 95% of primary and secondary infections, respectively, when serum specimens were tested as pairs. When tested as single specimens, the diagnoses by ELISA and HI agreed in 41% and 52% of acute specimens of primary and secondary infections, respectively. The lower rate of concordance in acute-phase samples was due to the absence of detectable IgM in acute specimens collected at outpatient clinics. On the other hand, diagnoses by ELISA and HI agreed in 79% and 95% of primary and secondary infections when single convalescent specimens were used. Analysis of the discordant results between the two tests revealed that the interpretation by the IgM-IgG ratio agreed better with HI classifications practised by some investigators than it did with the WHO. PMID- 1939503 TI - Generation of mammalian cells expressing stably measles virus proteins via bicistronic RNA. AB - The proteins of measles virus are believed to be cytotoxic, and have never been expressed stably from the cloned genes in cultured cells. We found that measles viral proteins can be expressed via a bicistronic RNA. The dominantly selectable DHFR* protein-coding region encoding a mutant dihydrofolate reductase was inserted into the 3'-untranslated regions of the measles viral genes encoding nucleoprotein (N), matrix (M) protein, and hemagglutinin (H). The tandemly arranged cistrons were placed under control by the inducible promoter of human metallothionein IIA gene, or the noninducible early promoter of simian virus 40. Upon transfecting into mammalian cells, these gene constructs synthesized bicistronic RNAs. The downstream DHFR* gene conferred resistance to methotrexate (MTX). Cells that survived MTX selection expressed stably the N, M, or H protein of measles virus. Expression of N protein was further inducible by cadmium chloride treatment. This system will be useful for studying the protein functions of measles virus, and could be applied to express other potentially toxic gene products. PMID- 1939504 TI - A microcomputer program simulating rate zonal centrifugation. PMID- 1939505 TI - Detection and identification of human influenza viruses by the polymerase chain reaction. AB - A series of oligonucleotide primers are described which hybridize to conserved regions of influenza virus cDNA and prime DNA synthesis in Taq polymerase catalyzed amplification reactions (PCR). Primers were designed to hybridize as nested pairs and, following a two-step amplification, produce uniquely sized DNA fragments diagnostic for viral type and subtype. Influenza A and B matrix-protein genes and the influenza C haemagglutinin gene were targets for the type-specific primers. Subtype-specific primers targeted conserved sequences within the three haemagglutinin or two neuraminidase subtypes of different human influenza isolates. The utility of this method was demonstrated using computer search methods and by accurately amplifying DNA from a variety of influenza A, B, and C strains. Type-specific primer sets showed a broad type specificity and amplified DNA from viral strains of unknown sequence. Restriction mapping and DNA sequencing showed that fragments amplified in this manner derived from the input template, confirming the accuracy of the method and demonstrating how PCR can be used to quickly derive sufficient sequence information for analysis of viral relatedness. Subtyping primers were able to distinguish accurately between the three haemagglutinin (H1, H2, H3) and two neuraminidase (N1, N2) alleles of human influenza A isolates. Again DNA was amplified from viruses of unknown sequence confirming that most of these primer sets may prove useful as broad range subtyping reagents. In order to simplify the work associated with analysis of many samples, we have also devised a rapid method for the isolation of viral RNA and synthesis of cDNA. Using this 'mini-prep' technique, it is possible to detect, amplify, and identify picogram quantities of influenza virus in a single day, confirming that PCR provides a useful alternative to existing methods of influenza detection. PMID- 1939506 TI - Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24- or 96-well plates. AB - Titers of lymphocytic choriomeningitis virus (LCMV) were determined on adherent fibroblast cell lines in 24- or 96-well plates. After absorption of virus by cells and 48 h incubation under a methylcellulose overlay, cell monolayers were fixed with 4% formaldehyde in phosphate-buffered saline, permeabilized by incubation in 0.5% Triton X-100 in balanced salt solution and then stained with a monoclonal rat anti-LCMV and a peroxidase-labeled second stage antibody. The sensitivity of the assay is within a factor of 2-4 of conventional plaquing methods. The method also detects poorly or non-plaquing LCMV isolates, and therefore drastically reduces the need for titration of LCMV in mice. The method is quicker (2-3 days), as compared to conventional methods (4-6 days) and less expensive in terms of work and materials. PMID- 1939508 TI - Stability and extractability of double-stranded RNA of pangola stunt and sugarcane Fiji disease viruses in dried plant tissues. AB - When leaves infected with pangola stunt virus (PaSV) were dried at 23, 37, 50, 70 or 105 degrees C, the dsRNA was stable and could be extracted after aerobic storage at room temperature for 1 month, although at 105 degrees C the amount obtained was reduced. The dsRNA was also recovered after leaves were freeze dried and stored in vacuo at room temperature for 6 months, or were dried and stored aerobically at room temperature for 10.5 months. dsRNA of sugarcane Fiji disease virus (FDV) was also stable when infected leaves were dried at 23, 37, 50 or 105 degrees C and stored aerobically for 3 months or for at least 6 months when infected leaves were dried at 70 degrees C. The unexpected high stability and extractability of both PaSV and FDV dsRNA when dried in leaves at low or high temperatures and stored at room temperature indicate that these, and probably other plant-infecting reoviruses, can be transported readily in desiccated host tissue between different countries for later extraction and comparison of their dsRNAs. PMID- 1939507 TI - Purification of epizootic haematopoietic necrosis virus and its detection using ELISA. AB - Epizootic haematopoietic necrosis virus (EHNV) was grown in Bluegill fry (BF-2) cells and purified using differential and gradient centrifugation. The lower band (B2) from 15-60% sucrose gradients contained infective EHNV but few contaminating cell components when assessed by electron microscopy, SDS-PAGE, and Western blotting using anti-BF-2 serum and anti-B2 serum. Both rabbit and sheep anti-B2 sera precipitated B2 in agarose gel immunodiffusion and detected EHNV in cell culture supernatant when used in an indirect antigen-capture ELISA. Rabbit anti B2 serum was used as capture antibody while sheep anti-B2 serum was used to detect viral antigen. Pre-adsorption of diluted sheep anti-B2 serum using BF-2 cell lysate greatly improved the specificity and sensitivity of the technique. PMID- 1939509 TI - Comparison of Immobilon-N membrane and other membranes for the detection of HIV-1 genome in high risk patients using PCR. AB - The polymerase chain reaction (PCR) was used for detection of the HIV-1 genome from the peripheral blood lymphocytes of high risk patients. The gag regions of HIV-1 (SK38-SK39) were chosen to amplify viral DNA and the amplified products were spotted onto membrane filters and hybridized with a 32P-labeled SK19 probe. Nitrocellulose, nylon and polyvinylidene difluoride (PVDF) membrane filters were used and compared in dot-blot hybridization. PVDF (Immobilon-N, trade name) filter membranes were demonstrated to be the best membranes on the basis of hybridization data and showed a stronger signal on autoradiograms than the other two types (nitrocellulose and nylon). PMID- 1939510 TI - Diagnosis of measles by fluorescent antibody and culture of nasopharyngeal secretions. AB - An indirect fluorescent antibody test (IFA) was evaluated using commercial mouse anti-measles monoclonal antibody and FITC-labeled goat anti-mouse immunoglobulin. For measles isolation, specimens were inoculated into Rhesus monkey kidney (RMK) cells and, when available, CV-1 cells. 381 specimens were tested by IFA and 408 specimens were cultured from patients suspected of having measles. For the 381 specimens tested by both methods, IFA and culture were positive for 31%, culture alone for 14%, IFA alone for 15%, and both negative for 40%. This study indicates that both IFA and culture are required for maximum measles virus detection. Of the positive specimens, 48% were detected either by IFA only (24%) or culture only (24%). IFA was positive in 69% of the culture-positive specimens and therefore, provided rapid diagnosis for many patients. PMID- 1939511 TI - Determination of HBsAg subtypes in different high risk populations using monoclonal antibodies. AB - Monoclonal antibodies with restricted specificity were used in a modified commercial enzyme immunoassay for detection of HBsAg to subtype HBsAg in sera from 122 Southeast Asian refugees entering the United States, 62 inmates of a correctional facility, and 19 homosexual men. This method was able to classify HBsAg as aywl-2, ayw3, ayw4, ayr, adw2, adw4, or adr. The HBsAg subtype was identified in 183 (90.1%) of the serum samples, but the serum HBsAg concentration was too low to determine the subtype for the 20 (9.9%) remaining samples. Among the Southeast Asian refugees, aywl-2 was demonstrated in 35 (33.0%) of the subtyped serum samples, the adw2 subtype was identified in 33 (31.1%) sera, adr was detected in 37 (34.9%) sera, and the adw 4 subtype as found in 1 (0.9%). The most common subtypes in Vietnam, Laos, and Cambodia were aywl-2, adw2, and adr, respectively. In prison inmates, the ayw3 subtype accounted for 31 (52.5%) of the subtyped serum samples, an ayw2 variant and the adw2 subtype were each found in 13 (22.0%) sera, and the aywl-2 subtype was detected in 2 (3.4%) sera. Many of these inmates admitted intravenous drug use. Among homosexual men, the adw2 subtype was identified in 16 (88.9%) of the subtyped serum samples and the ayw3 subtype was detected in 2 (11.1%) sera. This subtyping method can distinguish between most of the nine major HBsAg subtypes and can be easily performed with these monoclonal antibodies and commercially available reagents. PMID- 1939512 TI - Epidemiology of measles in the Cameroons between 1984 and 1986: comparison of the effectiveness of different serological methods in rural regions. AB - Epidemiological studies were carried out in Yaounde and in Ngaoundere from 1984 to 1986, in an attempt to develop adequate methods of collecting blood from small children and of diagnosing measles appropriate to conditions in the field. Alternative methods were necessary since classical methods used in modern laboratories are unsuitable in rural regions. Each study was carried out on a representative sample of 6- to 36-months-old infected children seen at consultation. This group was chosen because it suffers the highest mortality rate. The blood was obtained by digital puncture on blotting paper because venepuncture required sterile equipment and also the establishment of a cold chain for transporting the samples to the laboratory. The first criteria examined were the relative titers of sera taken by finger prick. Four serological techniques were used: indirect immunofluorescence (IIF), indirect immunoperoxidase (IIP), hemagglutination inhibition (HAI) and ELISA. Antimeasles antibodies were detected in 12% of infected children using IIF and in 18% using IIP. When sera were examined by HAI the percentage of positives was 54% and by ELISA 75%. These results clearly indicate that ELISA is the most effective and practical technique for diagnosing measles under field conditions. PMID- 1939514 TI - Pituitary enlargement with suprasellar extension in functional hyperprolactinemia due to lactotroph hyperplasia: a pseudotumoral disease. AB - Beside the well characterized PRL-secreting adenomas, a wide spectrum of functional hyperprolactinemic states exists. We describe here five women, 21-38 yr old, all suspected of having a PRL-secreting adenoma because of a pseudotumoral appearance of the pituitary on computerized tomographic (CT) scan or magnetic resonance imaging (MRI). Four had oligomenorrhea with or without galactorrhea, one had amenorrhea with galactorrhea, and two complained of infertility. In the same patient, basal plasma PRL levels were variable on different days, sometimes normal (mean +/- SEM, 11.3 +/- 1.5 micrograms/L), sometimes elevated (49 +/- 7 micrograms/L), but in all cases, a PRL response of large amplitude to TRH (6- to 8-fold increase in the basal value) was observed. Basal plasma levels of estradiol were within luteal phase normal values (0.41 +/- 0.13 pmol/L), while progesterone levels were low (1.92 +/- 0.47 nmol/L). CT scan or MRI showed an intrasellar mass with suprasellar extension, suggesting a tumoral process. However, the signal intensity was homogeneous, and on coronal views, the suprasellar extension was pyramidal and symmetrical, and the pituitary stalk was always in the midline. The five patients were operated on by the transsphenoidal route, but no adenoma was found. Surgical biopsies were taken in four cases, and lactotroph hyperplasia, i.e. enlarged cell cords consisting mainly of PRL cells, was found in three of them. One case displayed a continuum between areas of lactotroph hyperplasia and adenomatous PRL cells. We conclude that functional hyperprolactinemia may mimic on CT scan or MRI a PRL-secreting adenoma. PMID- 1939513 TI - Glycosylation of parathyroid hormone-related peptide secreted by human epidermal keratinocytes. AB - While the gene and mRNA transcripts encoding PTH-related peptide (PTHrP) have been well characterized, the actual secretory form(s) of the peptide is unknown. Accordingly, synthetic and recombinant PTHrPs employed to date for biological and immunological characterization have necessarily been of arbitrary lengths. No prior evidence for glycosylation of PTHrPs has been described. To define the naturally occurring form(s) of this peptide secreted by human epidermal keratinocytes, we have affinity purified, using an anti-PTHrP-(1-36) antibody column, human PTHrP secreted under conditions of protease protection. Human keratinocyte-conditioned medium collected without measures to protect against proteolytic degradation contains multiple PTHrP immunoreactive and bioactive species. In contrast, under conditions of protease protection, human keratinocyte conditioned medium contains a single 18,000 mol wt (Mr) form of the peptide. In contrast to recombinant and synthetic PTHrPs, which migrate as distinct, well focussed bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, this 18,000 Mr PTHrP displays the broad electrophoretic profile of a glycoprotein. Treatment of this peptide with trifluoromethanesulfonic acid, an agent that deglycosylates both O- and N-linked saccharides from their core proteins, shifted the Mr of the protein to approximately 10,000. In contrast, exposure of recombinant PTHrP-(1-141) to the same agent results in no change in electrophoretic mobility. These studies indicate that the 18,000 Mr species of PTHrP secreted by human epidermal keratinocytes is a glycoprotein. PMID- 1939515 TI - Hormone and receptor studies: relationship to linear growth in childhood and puberty. AB - Preliminary data suggested different patterns of hormonal control of linear growth in males and females. To better define these patterns, serum samples were collected from 75-125 boys and a similar number from girls for each year of age between 3-16 yr (n = 2416). Fewer samples were collected from 2-yr-olds, newborns, and adults (n = 151). Samples for each age were aliquoted, combined, and assayed for GH, GH-binding protein (GHBP), insulin-like growth factor-I, and testosterone. GHBP, expressed as a percentage of the [125I]GH bound, increased yearly in males and females, with no relationship to the secretion of sex hormones. The increase in binding of [125I]GH and, by inference, GH receptors occurred at a greater rate between the ages of 2-10 yr than between 10-16 yr (in terms of absolute binding, 1.2 +/- 0.11% vs. 0.38 +/- 0.04% yearly; P less than 0.001). In each age group, however, the increase in GHBP exhibited a strong positive correlation with linear height (r = 0.96-0.98 in males; r = 0.92-0.99 in females). Before puberty, GH and insulin-like growth factor-I concentrations were consistently greater in females. Between 10-16 yr of age, height velocity (centimeters of growth per yr) correlated strongly with GH in girls (r = 0.86), but did not correlate with GH in boys of a similar age (r = -0.13). The major pubertal growth spurt in males strongly correlated with a rise in serum testosterone concentration beginning at age 11 yr (r = 0.92). Small peaks of GH secretion before and after the major period of accelerated growth in males possibly prolonged the major growth phase, but did not initiate it. PMID- 1939517 TI - Role of tumor necrosis factor-alpha and interferon-gamma as growth factors to the human fetal beta-cell. AB - The effects of the cytokines tumor necrosis factor-alpha and interferon-gamma on the adult beta-cell have been well described: a reduction of insulin secretion and content and death of the cell. For this reason and because these cytokines may be released from activated lymphocytes and macrophages that infiltrate islets in insulin-dependent diabetes, they have been implicated in the pathophysiology of this form of diabetes. As to whether the human fetal beta-cell, which differs from the adult beta-cell in not releasing insulin in response to the nutrient glucose and not being adversely affected by the toxin streptozotocin, is similarly affected is unknown. To examine this question we cultured monolayers of a single cell suspension of human fetal pancreas in the presence or absence of 1000 U/mL of these cytokines for 7 days. Chronic insulin release was enhanced for the first 2 days of culture, but unchanged thereafter. Acute insulin release in response to the secretagogue theophylline (10 mM) was enhanced on day 7, but not earlier. There was an increase in the insulin content of the cells by the fourth day, probably due to an increase in the number of beta-cells present (45 +/- 5% vs. 22 +/- 3%). Microscopically, non-beta-cells also seemed to increase in number; there was an increase in both DNA and cell number by the seventh day. In contrast to these beneficial effects on the human fetal beta-cell, treatment of adult rat insulinoma cells, represented by RIN-m5F cells, resulted in inhibition of insulin secretion during the first day of culture and subsequent death of 86% of the cells by the sixth day of culture. It is hypothesized that the functional immaturity and lack of normal (adult) metabolic activity of the human fetal beta cell somehow confers protection on these cells from the cytotoxic effects of tumor necrosis factor-alpha and interferon-gamma. Indeed, our findings suggest that these cytokines may be trophic for the developing beta-cell. PMID- 1939516 TI - Effects of pituitary-testicular axis suppression in utero and during the early neonatal period with a long-acting luteinizing hormone-releasing hormone analog on genital development, somatic growth, and bone density in male cynomolgus monkeys in the first 6 months of life. AB - The specific role of late fetal and early neonatal gonadotropins and/or sex steroids on genital development, linear growth, and bone mass accretion remains unclear. To investigate this, we attempted to selectively suppress pituitary testicular activation from midgestation through early infancy with a long-acting LHRH agonist (LHRHA), D-Trp6,Pro9-NEt-LHRH, in microspheres. The agonist was injected sc on days 72-81 in utero, on day 1 of life, and 3 months postnatally in male cynomolgus monkeys. Control animals were treated with placebo. We then examined the consequences of such an intervention in the first 6 months of life. In the LHRHA-treated animals, marked suppression of plasma testosterone and gonadotropin levels were evident in the first 3 months of life compared to control values. The mean testicular volumes of the LHRHA group were significantly lower at birth and in the first 2 months of life than those of the placebo group (P less than 0.05). However, by 4 months of age, the mean testicular volumes of the two groups were comparable. Similarly, the mean stretched phallic lengths of the LHRH approximately A group were significantly lower than those of the placebo group throughout the first 6 months of life (P less than 0.05). By contrast, LHRHA treatment had no effect on somatic growth, as mean body weights, total body lengths, and trunk lengths of the two groups were similar over the first 6 months of life. Mean bone widths and densities of the distal third of the left radius and the left midfemur were similar in the two groups at 1 and 6 months of life. We conclude that pituitary-testicular axis suppression with a long-acting LHRHA in utero and during early infancy results in markedly stunted penile and testicular growth without affecting general somatic growth and bone density of appendicular cortical bone in the cynomolgus monkey in the first 6 months of life. Thus, an intact fetal and neonatal pituitary-testicular axis is critical for normal genital growth. However, the sex steroid requirement for maintenance of bone mineral content of appendicular cortical bone may be lower than that necessary for normal genital development. PMID- 1939518 TI - Inverse relation between iodine intake and thyroid blood flow: color Doppler flow imaging in euthyroid humans. AB - High intake of iodine inhibits iodide trapping, iodide organification, and hormone release from the human thyroid. We investigated whether iodine intake also affects thyroid blood flow, as was suggested by a recent study in euthyroid rats. With a Color Doppler device we made 14 consecutive Duplex-Doppler registrations of both superior thyroid arteries in 10 euthyroid volunteers during baseline iodine intake (1 week), iodine restriction (2 weeks), return to baseline (1 week), and iodine excess (1 week; 80 mumol sodium iodide/day). Vessel diameters and mean flow velocity were measured on videotape recordings by a "blinded" observer. Baseline iodide excretion was 0.88 +/- 0.38 (+/- SD) mumol/day. Mean flow velocity was 13.9 +/- 4.1 cm/s, and vessel diameter was 1.07 +/- 0.22 mm. Blood flow was 7.7 +/- 3.8 mL/min.superior thyroid artery. During the low iodine diet, excretion dropped to 0.49 +/- 0.16 mumol/day, and blood flow increased to 11.0 +/- 5.0 mL/min (P less than 0.001), remaining elevated (10.3 +/ 4.4 mL/min) during the second baseline diet. During high iodide intake, blood flow averaged 5.8 +/- 3.4 mL/min (P less than 0.001), and the expected decrease in thyroid hormone levels and increase in TSH were seen. We conclude that thyroid blood flow responds inversely, and independently from TSH, to changes in iodine intake in euthyroid humans. PMID- 1939519 TI - Insulin-resistant diabetes mellitus and hypermetabolism in mandibuloacral dysplasia: a newly recognized form of partial lipodystrophy. AB - Mandibuloacral dysplasia (MAD) is a syndrome characterized by partial lipodystrophy and a distinct phenotype, which includes progressive osteolysis of the mandible and clavicles, cutaneous atrophy, joint contractures, and diabetes mellitus. We now describe the results of hyperinsulinemic glucose clamps performed in conjunction with indirect calorimetry in two subjects with MAD. At a glucose level of 5 mmol/L and insulin concentration of over 6.5 x 10(4) pmol/L, glucose disposal rates were less than 20% of maximum insulin-stimulated glucose disposal in five nondiabetic controls. Basal hepatic glucose output was elevated in the two patients and was incompletely suppressed by a 1200 mU/m2.min infusion of insulin. Glucose and lipid oxidation rates were inappropriately elevated, reflecting marked hypermetabolism. Pharmacological concentrations of insulin failed to normally suppress lipid oxidation, diminish FFA levels, or adequately suppress glucagon levels. In summary, MAD is a unique form of lipodystrophic diabetes characterized by typical somatic features, extreme insulin resistance, and marked hypermetabolism. PMID- 1939520 TI - Plasma beta-endorphin in neonates: effect of prematurity, gender, and respiratory status. AB - A consecutive cohort of 87 infants (46 infants less than 37 weeks gestational age and 41 term infants greater than or equal to 37 weeks gestation) admitted to the Neonatal Intensive Care Unit (NICU) and a convenience cohort of 27 term well babies at the University of Nebraska Medical Center (Omaha, NE) were evaluated for plasma beta-endorphin (beta E) levels during the first 4 h after birth. Demographic data, maternal history, and respiratory status at the time of sampling as well as development of documented apneic episodes during the initial hospitalization were analyzed for all infants. All NICU infants had higher plasma beta E levels than the control infants. Premature infants had significantly higher neonatal plasma beta E levels than term infants in either the control or NICU groups, but the response was gender specific; premature males had higher plasma beta E than premature females (P = 0.008). Perinatal stress, including respiratory problems, was associated with the increase in plasma beta E, but prematurity and being male were significantly predictors of an elevated plasma beta E level. Immaturity in respiratory control, as evaluated by the development of documented apneic episodes during the infant's initial hospitalization, did not correlate with an elevated perinatal plasma beta E level. PMID- 1939521 TI - Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. AB - Magnesium (Mg) deficiency in man may result in hypocalcemia, impaired PTH secretion, and low serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D]. To determine whether these changes are due to selective Mg depletion, we studied 26 normal subjects before and after a 3-week low Mg (less than 1 meq/day) diet. This diet induced Mg deficiency, as demonstrated by a fall in pre- to postdiet serum Mg levels from 0.80 +/- 0.01 to 0.61 +/- 0.02 mmol/L (P less than 0.001), an increase in Mg retention from 11 +/- 4% to 62 +/- 4% (P less than 0.001), and a fall in red blood cell free Mg2+ from 205 +/- 10 to 162 +/- 7 microM (P less than 0.001). Serum calcium (Ca) fell significantly from 2.36 +/- 0.02 to 2.31 +/- 0.03 mmol/L (P less than 0.05), and serum 1,25-(OH)2D fell from 55 +/- 4 to 43 +/ 3 pmol/L (P less than 0.05). PTH secretion was impaired, as demonstrated by a fall or no change in serum PTH in 20 of 26 subjects despite a fall in the serum Ca and Mg. In addition, an iv injection of Mg in eight subjects after the diet resulted in a significant rise in PTH from 15 +/- 2 to 19 +/- 2 ng/L (P less than 0.01), whereas a similar injection given to six of the subjects before the diet resulted in a significant fall from 28 +/- 5 to 13 +/- 3 ng/L (P less than 0.001). The fall in serum 1,25-(OH)2D may be due to both the decrease in PTH secretion and a renal resistance to PTH. PTH resistance was suggested, as no increase in serum 1,25-(OH)2D was observed in the six subjects in which the PTH concentration rose by mean of 68% after the diet. Also, the rise in serum 1,25 (OH)2D after a 6-h human PTH-(1-34) infusion was significantly less after Mg deprivation. The results demonstrate that mild Mg depletion can impair mineral homeostasis and may be implicated as risk factor for osteoporosis in disorders such as chronic alcoholism and diabetes mellitus, in which Mg deficiency and osteoporosis are both common. PMID- 1939522 TI - Decreased metabolic clearance of endogenous growth hormone and specific alterations in the pulsatile mode of growth hormone secretion occur in prepubertal girls with Turner's syndrome. Genentech Collaborative Group. AB - We have used deconvolution analysis to test the hypothesis that specific facets of GH secretion and clearance differ in young patients with Turner's syndrome and normal prepubertal girls. To this end, we sampled blood at 20-min intervals for 12 h overnight in 50 girls, 37 of whom had Turner's syndrome and 13 of whom were healthy Tanner stage I controls. Deconvolution analysis revealed that the half life of endogenous GH in Turner's syndrome was significantly prolonged at 14 +/- 0.93 vs. 11 +/- 0.44 min in normal girls (P = 0.029). The number of significant GH secretory bursts was reduced in Turner's patients to 4.7 +/- 0.27 vs. 6.8 +/- 0.60 events/12 h in healthy girls (P less than 0.01). GH secretory burst half duration was significantly prolonged in Turner's syndrome, viz. 23 +/- 1.3 vs. 15 +/- 0.87 min (controls; P less than 0.001). The changes in GH secretory burst frequency, duration, and half-life were specific, since neither the mass of GH secreted per burst nor the maximal rate of GH secretion attained per burst (amplitude of the secretion pulse) was significantly different in the 2 study groups. Thus, although 12-h GH secretion rates corrected for body weight were similar (3.9 +/- 0.76 in Turner's patients and 3.3 +/- 0.76 micrograms/L.kg/12 h in the control girls), equivalent GH production rates were achieved by different mechanisms in the 2 groups. We conclude that specific alterations in GH secretory burst frequency and duration and endogenous GH half-life can be documented in young girls with Turner's syndrome. PMID- 1939523 TI - Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. AB - Mean plasma GH concentrations are controlled by the frequency, amplitude, and duration of underlying GH secretory bursts as well as by the half-life of endogenous GH. We investigated the specific mechanisms that subserve the clinically recognized negative effects of age and adiposity on mean serum GH concentrations. To this end, 21 healthy men, aged 21-71 yr, who were of nearly normal body weight underwent blood sampling at 10-min intervals for 24 h. Deconvolution analysis was used to estimate specific features of GH secretion and clearance. Compared to younger men, the older tertile of men had significant reductions in 1) GH secretory burst frequency, 2) the half-life of endogenous GH, and 3) the daily GH secretory rate, but not 4) GH secretory burst half-duration, amplitude, or mass. Linear regression analysis disclosed that age was a major negative statistical determinant of GH secretory burst frequency (r = -0.80; P = 0.005) and endogenous GH half-life (r = -0.70; P = 0.024). Body mass index, an indicator of relative obesity, was a significant negative correlate of GH half life (P = 0.045) and GH secretory burst amplitude (P = 0.031). Age and body mass index each correlated negatively with the daily GH secretion rate (P = 0.0031 and P = 0.027, respectively), and together accounted for more than 60% of the variability in 24-h GH production rates (r = -0.78; P = 0.00056). On the average, for a normal body mass index, each decade of increasing age attenuated the GH production rate by 14% and the GH half-life by 6%. Conversely, each unit increase in body mass index, at a given age, reduced the daily GH secretion rate by 6%. We conclude that age and relative adiposity are distinct and specific correlates of individual attributes of GH secretion and clearance in men. PMID- 1939524 TI - The influence of academic stress and season on 24-hour concentrations of growth hormone and prolactin. AB - Stress has been considered a physiological regulator of GH and PRL secretion in humans. The stressors used in studies have often been extreme. The influence of commonplace stressors on the endocrine system has not been clarified. Therefore, to better define the role of commonplace stressors on GH and PRL secretion, we evaluated the effect of examination stress on GH and PRL secretion in 37 male medical students. We performed hourly sampling for 24 h for GH and PRL 4 weeks before, during exam week, and 2 weeks after major examinations in the fall and spring of their first year. Stress, as evaluated by the Perceived Stress Scale (PSS), increased as expected during examination weeks, but there was no correlation between the PSS scores and mean day or night GH and PRL secretion. Twenty-four-hour GH and PRL secretion was not significantly altered during examinations in either fall or spring. A significant seasonal influence, however, was noted on GH secretion, with both daytime and nocturnal GH secretion being consistently higher in the Fall than in the Spring. We conclude that examination stress does not significantly influence mean daytime or nocturnal GH and PRL concentrations. We suggest that serum GH and PRL levels may not be significantly altered in man by commonplace stressors. Also, seasonal effects may be operative in the control of human GH secretion. PMID- 1939525 TI - Naloxone increases the frequency of pulsatile luteinizing hormone secretion in women with hyperprolactinemia. AB - The ability to change the frequency and amplitude of pulsatile GnRH secretion may be an important mechanism in maintaining regular ovulatory cycles. Hyperprolactinemia is associated with anovulation and slow frequency LH (GnRH) secretion in women. To assess whether the slow frequency of LH (GnRH) secretion is due to increased opioid activity, we examined the effect of naloxone infusions in eight amenorrheic hyperprolactinemic women (mean +/- SE, serum PRL, 160 +/- 59 micrograms/L). After a baseline period, either saline or naloxone was infused for 8 h on separate days, and LH was measured in blood obtained at 15-min intervals. Additional samples were obtained for plasma FSH, PRL, estradiol, and progesterone. Responses to exogenous GnRH were assessed at the end of the infusions. LH pulse frequency increased in all subjects from a mean of 4.0 +/- 0.5 pulses/10 h (mean +/- SE) during saline infusion to 8.0 +/- 1.0 pulses/10 h during naloxone infusion (P less than 0.01). LH pulse amplitude did not change, and mean plasma LH increased from 7.4 +/- 0.8 IU/L (+/- SE) to 11.2 +/- 1.5 IU/L during naloxone (P less than 0.01). A small but significant increase was seen in mean plasma FSH. Plasma PRL, estradiol, and progesterone were unchanged by naloxone infusion. These data suggest that elevated serum PRL reduces the frequency of LH (GnRH) secretion by increasing hypothalamic opioid activity and suggest that the anovulation in hyperprolactinemia is consequent upon persistent slow frequency LH (GnRH) secretion. PMID- 1939526 TI - Interactions between oleic acid and drug competitors influence specific binding of thyroxine in serum. AB - Long chain nonesterified fatty acids and various drugs may share albumin-binding sites in common. We questioned whether serum binding of T4 could be indirectly influenced by displacement of drug competitors from these sites by nonesterified fatty acids. The influence of oleic acid on drug-induced inhibition of [125I]T4 binding was measured by equilibrium dialysis, using undiluted serum in order to avoid dilution-related artefacts. Oleic acid (1 mmol/L) alone did not inhibit serum protein binding of T4, but this concentration augmented the inhibitory effects on T4 binding of diflunisal, mefenamic acid, meclofenamic acid, and aspirin. This effect increased with increasing concentrations of mefenamic acid, meclofenamic acid, and furosemide. The T4-displacing effect of fenclofenac was not augmented by oleic acid. The mechanism of these interactions was studied by examining 1) oleic acid effects on drug binding, and 2) drug effects on oleic acid binding in undiluted serum. Increments in added oleic acid (0.5-2.0 mmol/L) progressively increased the mean unbound fractions of [14C]aspirin, [14C] diflunisal, and [14C]furosemide, but did not displace [14C]fenclofenac. At the relevant total and free drug concentrations, the inhibitory effect of oleic acid on drug binding and its influence on drug-induced displacement of T4 were concordant in the order: meclofenamic acid greater than aspirin greater than mefenamic acid greater than diflunisal greater than furosemide greater than fenclofenac. In contrast, drug-induced increases in the unbound fraction of [14C]oleic acid did not correlate with augmentation of T4 displacement. We conclude that synergistic effects of oleic acid and drugs on T4 binding result from drug displacement by oleic acid, rather than the reverse effect. Hence, substances that increase the unbound concentration of a competitor by displacing it from albumin can increase its T4-displacing potency. Interactions between various ligands may exert a greater hormone-displacing effect than the sum of each alone. PMID- 1939527 TI - 1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial. AB - An unexplained loss of muscle strength occurs with aging. Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [1,25-(OH2)D3] to persons with low serum concentrations can improve strength. To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [1,25-(OH2)D3], we conducted a randomized, controlled, double blinded trial in 98 men and women volunteers over 69 yr old. Treatment consisted of 0.25 micrograms 1,25-(OH)2D3, orally, twice per day or identical placebo for 6 months. Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer. There was no difference between the two groups at 1 week, 1 month, or 6 months of treatment in any of the measures of muscle strength. We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons. Further research is needed to determine the etiology of the decline in muscle strength associated with aging. PMID- 1939528 TI - Serum bioactive follicle-stimulating hormone-like activity in human pregnancy is a methodological artifact. AB - Serum from pregnant women has been shown to contain both FSH-like and FSH antagonistic activities when measured by an in vitro bioassay based upon FSH dependent aromatase activity of immature rat Sertoli cells. In the present study we further tested the hypothesis that the FSH-like bioactivity of pregnancy serum was due to an authentic aromatase stimulator. A potent inhibitor of aromatase which completely blocked the FSH action on Sertoli cells had no effect on the bioactivity of pregnancy serum. Experiments using conversion of tritiated testosterone to estradiol showed that the factor did not stimulate aromatase activity in rat Sertoli cells. After incubation with pregnancy serum, equally high amounts of estradiol were measurable in the medium in both the absence and presence of Sertoli cells. The activity was almost completely lost after charcoal treatment or ether extraction of the serum and was shown to probably be due to the release of endogenous estrogens by the carrier proteins in the incubation medium of the Sertoli cell assay. These data suggest that the FSH-like bioactivity in serum from pregnant women is an artifact due to nonspecific interference(s) in the bioassay. PMID- 1939529 TI - Testicular tumors in congenital adrenal hyperplasia: steroid measurements from adrenal and spermatic veins. AB - The present study reports the case of a 25-yr-old man with congenital adrenal hyperplasia due to 21-hydroxylase deficiency in whom bilateral testicular tumors did not regress after suppressive treatment with dexamethasone. Catheterization of left testicular and adrenal veins confirmed the enzyme deficiency in the gonadal lesions. The presence of specific 11 beta-hydroxylated steroids (11 beta hydroxyandrostenedione, 21-deoxycortisol, and 21-deoxycorticosterone) in the gonadal vein demonstrated the adrenal nature of the testicular tumor. In addition, catheterization allowed further study of the secretion of mineralocorticoids and androgens in the adrenal venous effluent. Plasma levels of deoxycorticosterone were increased in the peripheral vein and decreased in the adrenal vein, confirming the conversion of progesterone by peripheral 21 hydroxylase activity. Plasma levels of delta 5-3 beta-hydroxysteroids, particularly dehydroepiandrosterone and its sulfate, were very low, suggesting a sustained stimulation of 3 beta-hydroxysteroid dehydrogenase activity. This study documents that in patients with congenital adrenal hyperplasia and bilateral testicular tumors, catheterization of a gonadal vein measuring specific 11 beta hydroxylated steroids confirms the adrenal nature of the gonadal lesions. PMID- 1939530 TI - Localization and secretion of inhibin/activin subunits in the human and subhuman primate fetal gonads. AB - Little is known about the ability of the fetal primate gonads to produce inhibin/activin. We investigated the presence of the alpha-, beta A-, and beta B subunits of inhibin/activin in fetal human (16-23 weeks gestational age) and rhesus monkey (days 150-157 of gestation; term = 165 days) testes and ovaries by immunocytochemistry. The regulation of alpha-inhibin secretion by gonadotropins was studied in fetal testicular cultures. In the human fetal testis, alpha subunit immunostaining was found in interstitial and intratubular cells, while beta A- and beta B-subunit immunostaining occurred in clusters of Leydig cells that were clearly demarcated from groups of Leydig cells that were immunonegative. In the late gestational monkey testis, the alpha-subunit was localized in tubular cells, and the beta B-subunit was present in the tubules and interstitium. Testicular cells from midgestation human testes secreted detectable immunoreactive alpha-inhibin in response to FSH and hCG stimulation; alpha inhibin levels were significantly higher after hCG than FSH. In contrast, levels of alpha-inhibin secreted by rhesus monkey testicular cells were significantly increased by FSH, but not hCG. In the ovary, only weak beta B-subunit immunoreactivity was detected in granulosa cells of a few primary follicles from midgestational human fetal ovaries. In contrast, all three subunits were found in granulosa cells of numerous primary and secondary follicles in the late gestation rhesus monkey ovary. In light of recent evidence that inhibins/activins have actions on gonadal differentiation and growth modulation in vitro, as well as endocrine effects on the fetal pituitary, we propose that these proteins may have intragonadal and endocrine roles in human and subhuman intrauterine gonadal development. PMID- 1939531 TI - Clinical review 27: Effects of hormonal replacement on lipids and lipoproteins in postmenopausal women. PMID- 1939532 TI - Type I pseudohypoaldosteronism includes two clinically and genetically distinct entities with either renal or multiple target organ defects. AB - Type I pseudohypoaldosteronism (PHA) is a hereditary disease characterized by salt wasting resulting from target organ unresponsiveness to mineralocorticoids. We have studied two kindreds including a total of nine patients with PHA. In kindred I, the propositus presented with renal salt wasting in infancy (vomiting, failure to thrive, short stature, hyponatremia, hyperkalemia) and responded dramatically to a high salt diet (2.5 g/day). Sodium supplementation was discontinued at the age of two. In seven additional family members from three generations, clinical expression of PHA varied from asymptomatic to moderate. In affected members (propositus, mother, and two brothers), hyperaldosteronism persisted over 13 yr; however, the PRA decreased gradually to near normal values. Persistent hyperaldosteronism in the face of a decrease in PRA indicated the development of tertiary hyperaldosteronism due to autonomously functioning zona glomerulosa. The pedigree was consistent with an autosomal dominant mode of transmission with variable expression. In kindred II, the propositus, who was the product of a consanguineous marriage, developed severe renal salt losing at age 9 days. She had also increased salivary and sweat electrolytes consistent with PHA resulting from multiple organ unresponsiveness to mineralocorticoids. Life threatening episodes of salt wasting recurred beyond the age of 2 yr. At 5 yr of age she still requires high amounts of salt supplements (14 g/day). A sister died at 9 days of age with PHA symptoms. Six close relatives (parents, three siblings, maternal uncle) showed no biochemical abnormalities. This pedigree was consistent with an autosomal recessive mode of inheritance. In view of the findings on these two kindreds and the analysis of those in the literature, we conclude that type I PHA includes two clinically and genetically distinct entities with either renal or multiple target organ defects. PMID- 1939533 TI - Diagnosis under random conditions of all disorders of the renin-angiotensin aldosterone axis, including primary hyperaldosteronism. AB - Theoretically, the relationship between plasma aldosterone (PA) and PRA in normal subjects under random conditions should differ from that in patients with primary hyperaldosteronism or primary adrenal failure, but should be similar to that in patients with secondary hyperaldosteronism or hyporeninemic hypoaldosteronism. PA, expressed as a function of PRA, the PA/PRA ratio, provides an index of adrenal sensitivity in normal subjects under routine conditions. The random PA/PRA ratios in patients with primary adrenal disorders did not overlap with those in normal subjects, patients with secondary adrenal disorders, hypertensive subjects, or other patients. A single elevated PA/PRA ratio, i.e. more than 920, associated with elevated PA in 4 patients or normal PA in 6 patients indicated primary hyperaldosteronism in 10 patients. However, 5 of 17 patients with chronic renal failure had elevated PA/PRA ratios, but did not have primary hyperaldosteronism. All 14 patients with secondary hyperaldosteronism had elevated PA associated with normal PA/PRA ratios. A single PA/PRA ratio of less than 28 associated with low PA in 18 patients and a normal PA in 1 patient indicated primary adrenal insufficiency, while a low PA associated with a normal PA/PRA ratio indicated hyporeninemic hypoaldosteronism in 7 patients. Fifty-nine patients with nonadrenal disorders other than renal failure had normal PA and PA/PRA ratios. Therefore, with the exception of patients with advanced renal failure, only a single blood sample is required to establish all diagnoses of disorders of the renin-angiotensin-aldosterone axis under random conditions. PMID- 1939534 TI - The steroid hormonal milieu of the undisturbed human fetus and mother at 16-20 weeks gestation. AB - The interrelations of steroid hormone levels in plasma and amniotic fluid from mothers and their undisturbed fetuses at early midgestation of human pregnancy have not been defined previously. We, therefore, studied 12 healthy mothers and their fetuses undergoing termination of pregnancy for social reasons at 16-20 weeks gestation. Fetal arterial and venous blood was obtained by direct vessel puncture through a fetoscope in the conscious sedated mothers immediately before termination of pregnancy. Simultaneously, maternal peripheral venous blood and amniotic fluid were collected. Aldosterone (Aldo), corticosterone (B), 11 deoxycorticosterone, progesterone (P), 17-hydroxyprogesterone (17OHP), 11 deoxycortisol, cortisol (F), and cortisone were simultaneously determined by specific RIA after extraction and chromatography. Positive fetal arterio-venous differences were found for F, B, and Aldo, whereas arteriovenous differences were negative for P and 17OHP. In amniotic fluid, six of the eight corticosteroids showed significantly lower levels during fetoscopy than during routine amniocentesis, as reported previously using the same analytical methods. The present study demonstrates that the undisturbed human fetus at 16-20 weeks gestation actively secretes the most important gluco- and mineralocorticoids, F, B, and Aldo, independent of the mother. P and 17OHP were shown to be primarily derived from placental production and supplied to the fetus as a source of F and Aldo biosynthesis. The fetoscopy procedure with premedication seemed to give rise to less stress to the fetus than routine amniocentesis without sedation. Fetoscopy is, therefore, an ideal method to study feto-maternal steroid interrelations in human pregnancy. PMID- 1939535 TI - Effects of sodium supplementation during energy restriction on plasma norepinephrine levels in obese women. AB - We tested whether sodium restriction would counteract the decrease in sympathetic nervous system activity usually associated with marked energy restriction. The effects of two levels of energy restriction, with different sodium intakes, on plasma norepinephrine (NE) levels while supine and in response to standing were studied. Twenty-two healthy normotensive obese female subjects (body mass index, 34 +/- 1 kg/m2; weight, 90 +/- 2 kg) followed one of three 3-week protocols: 1) total fasting with 80 mmol/day NaCl, 2) a very low energy diet (VLED) containing 1.7 MJ, 93 g protein, and 90 mmol Na/day, with an additional 60 mmol/day NaCl supplement, or 3) total fasting without NaCl (0 Na fast). At the end of the baseline isocaloric diet and of total fasts or VLED, pulse, blood pressure, and plasma NE were measured after 4 h of recumbency and 5 and 10 min after assuming the upright posture. These measurements were repeated after 1 L physiological saline was infused into the 0 Na fast subjects. Cumulative negative sodium balance was observed only in the 0 Na fasting subjects. Supine blood pressure decreased from baseline with fasting, but not with the VLED. The decreases in systolic pressure and increases in heart rate on standing observed with all diets were greatest with the 0 Na fast. Supine plasma NE (vs. baseline value) declined (P less than 0.05) with the VLED, remained unchanged with the Na supplemented fast, but increased with the 0 Na fast (P less than 0.05). The upright plasma NE values were highest in the 0 Na fast subjects, but lower after the saline infusion as well as in the subjects on the VLED. Thus, the decrease in NE due to energy restriction with normal sodium intake was counteracted by moderate sodium restriction, and levels increased with zero sodium intake. Therefore, sodium depletion can override the suppressive effect of energy restriction and, instead, increase the activity of the sympathetic nervous system, as reflected by plasma NE. PMID- 1939536 TI - Twenty-four-hour profile of plasma glucose and glucoregulatory hormones during normal living conditions in trained and untrained men. AB - Compared with untrained (UT) subjects, in trained (T) subjects the increased insulin sensitivity and decreased glucose induced insulin secretion would tend to promote health by decreasing glucose levels and insulin secretion whereas the increased food intake would tend to increase these variables. To study the net effect of training, blood was sampled from seven T and eight UT young men [VO2max: 76 +/- 2 (T) vs. 48 +/- 1 (UT) mL.kg-1.min-1] for 24 h during ordinary living conditions. Athletes exercised 204 +/- 20 min and ate 50% more calories and 130% more carbohydrate than UT subjects (P less than 0.05). However, 24-h integrated plasma concentrations of glucose, C-peptide, glucagon, free fatty acids, and glycerol as well as glycosylated hemoglobin levels were identical in T and UT subjects. Mean insulin concentration was 41% lower in T than in UT but levels differed significantly (P less than 0.05) only late during the night. Urinary excretion of pancreatic peptides paralleled plasma concentrations. In conclusion, during training adaptations in pancreas- and insulin-sensitive tissues allow the necessary increase in food intake without harmful hyperglycemia and overloading of beta-cells, but sparing of insulin secretion and reductions in glucose levels are only relative to food intake. However, training may be wholesome by increasing hepatic insulin extraction and thereby decreasing arterial insulin levels. Training-induced beta-cell adaptation is not caused by diminished average glucose levels. Finally, renal handling of insulin, C-peptide, and glucagon is not influenced by training. PMID- 1939537 TI - Counterregulatory adaptation to recurrent hypoglycemia in normal humans. AB - We evaluated the effect of antecedent hypoglycemia on glucose counterregulation during hypoglycemia in non-diabetic human subjects. In single hypoglycemia studies, glucose production [( 3H]3-glucose) and counterregulatory hormone concentrations were measured (after a 3.5-h baseline period of euglycemia) during 120 min of hypoglycemia (glucose clamped at 3.0 mmol/L). During the final 60 min of hypoglycemia, counterregulation resulted in significant increments in glucose production (12.88 +/- 0.83 mumol/kg.min), and plasma glucagon (IRG; 185 +/- 22 ng/L), GH (29.3 +/- 7.0 micrograms/L), cortisol (630 +/- 100 nmol/L), epinephrine (3.44 +/- 0.76 nmol/L), and norepinephrine (2.02 +/- 0.21 nmol/L). In the recurrent hypoglycemia experiment, an antecedent period of identical hypoglycemia was induced. Glucose counterregulation during the second of two periods of hypoglycemia (HYPO 2) was then compared to that in single hypoglycemia studies. During HYPO 2, there were decreased responses in Ra (by 32%; P less than 0.03), GH (by 67%; P less than 0.05), F (by 41%; P less than 0.03), and norepinephrine (by 20%; P = 0.03) compared to those in the single hypoglycemia study. In contrast, plasma IRG values were similar in the single hypoglycemia studies and HYPO 2, but were reduced relative to those during the first hypoglycemic period of recurrent hypoglycemia (IRG, 263 +/- 18 ng/L; P less than 0.025 vs. HYPO 2 and P less than 0.05 vs. single hypoglycemia). Our results suggest that 1) antecedent hypoglycemia may alter glucose counterregulation during hypoglycemia; and 2) recurrent hypoglycemia may result in alterations in reduction of hepatic glucose production. PMID- 1939538 TI - The efficiency and efficacy of IVF and GIFT. AB - Data relating to the rate of clinical pregnancy obtained with in-vitro fertilization--embryo transfer (IVF-ET) and gamete intra-Fallopian transfer (GIFT) are available for Australia, UK, USA and France. For IVF-ET the value is not affected by the indication but is affected by the age of the woman. The rate of spontaneous abortion, at approximately 20-25% also increases with age and is an important consideration in view of the increased age of patients undergoing IVF-ET. A take-home baby rate of 30% is obtained from an estimated 70% of clinical pregnancies leading to live births and an estimate of 42.8% pregnancies after three attempts. The greater number of oocytes transferred with GIFT may be associated with the increased frequency of multiple pregnancies. PMID- 1939539 TI - Epidermal growth factor receptor in human uterine tissues. AB - Epidermal growth factor receptor (EGFR) was studied in human endometrium and myometrium collected throughout the menstrual cycle (five follicular, five luteal specimens) by immunohistochemistry and quantitative ligand binding. EGFR was principally present on the cell surface of glandular epithelium of the endometrium. Staining was no different between the follicular and luteal phases. There was more EGFR binding in endometrium than myometrium by quantitative ligand binding in membrane preparations: endometrium, median = 92.5 fmol/mg protein (range 25.3-294) n = 10; myometrium, median = 43.0 fmol/mg protein (range 23.4 57) n = 10. There was no difference in the level of binding in the follicular and luteal phases. PMID- 1939540 TI - Effect of exogenous progesterone administration on the morphology of normally developing endometrium in the pre-implantation period. AB - The effects on endometrial morphology of a single, intramuscular dose of 100 mg of progesterone administered in the early luteal phase, between days LH + 1 and LH + 6, were studied in a group (n = 8) of normal, fertile subjects by morphometric techniques and transmission electron microscopy. While the dose of progesterone administered consistently resulted in an increase of salivary progesterone concentration to above the upper limit of the reference range, no significant effect on endometrial development was observed; in particular, endometrial development was not advanced. PMID- 1939541 TI - A scanning electron microscopic study of the human ovarian surface epithelium: characterization of two cell types. AB - The surface of the ovary has two types of epithelial cells. We have called these A and B cells and they are found in their own respective zones (A and B). To assess the scanning electron microscopic features of these cell types, 65 ovarian samples were collected from biopsies taken from 35 women with normal ovaries. Biopsies included developing follicles, corpora lutea and ovarian capsules. Type A cells were cuboidal and sometimes tall, with a mean diameter of 6.49 microns, and a mean density of microvilli of 6.48/microns 2. Type B cells, on the other hand, were flat squamous cells with broader and flat apices with mean diameters and microvillus density of 11.71 microns and 3.88/microns 2 respectively. The A and B zones were common to all surfaces including the distending follicle. Type A cells overlying the distended surface of a follicle had a mean diameter of 7.03 microns compared to a mean of 6.05 microns for the capsular surface. Type B cell diameters and the microvillus density of both types were more variable and did not differ significantly over any of the surfaces. We suggest that previous human studies which identified flattening of cells over the distending follicle were probably observing B cells. The relationship of the B zones to papillae and surface bridges on the ovarian surface, and the association of these with ovulation sites, suggests that B cells are probably metaplastic cells derived in response to chronic surface injury with ovulation. PMID- 1939542 TI - Recurrent empty follicle syndrome. AB - We report a case of recurrent empty follicle syndrome over two stimulated cycles in a patient having immunological infertility. All follicles contained follicular fluid but aspirated granulosa cells were rarely observed. No oocytes were obtained from a total of 24 follicles. PMID- 1939543 TI - The effects of clomiphene citrate upon ovulation and endocrinology when administered to patients with unexplained infertility. AB - Twenty-four couples with unexplained infertility were studied in a spontaneous cycle followed by a clomiphene citrate (CC) cycle (150 mg, days 5-9). All spontaneous cycles were ovulatory, as defined by follicular collapse determined by transvaginal sonography. In CC cycles, 6/24 (25%) cycles demonstrated luteinized unruptured follicles (LUF). In 2/6 LUF cycles there was no apparent luteinizing hormone (LH) surge. LUF cycles had significantly elevated LH levels in the follicular phase compared to ovulatory CC cycles. There was no apparent difference in serum oestradiol. In CC cycles multifollicular development occurred in 87.5% of cycles, with significantly elevated serum oestradiol. Luteinizing hormone and follicle-stimulating hormone were elevated in the follicular phase compared to spontaneous cycles. This study suggests a high incidence of LUF when CC is administered to ovulatory patients, and its use in patients with ovulatory infertility is questioned. PMID- 1939545 TI - Spontaneous pregnancies in two women with Laron-type dwarfism: are growth hormone and circulating insulin-like growth factor mandatory for induction of ovulation? AB - It has recently been claimed that growth hormone (GH) and insulin-like growth factors have a role in follicular development; different mechanisms of action have been proposed. Of late, many investigators have been led by these findings to use GH and growth hormone-releasing hormone (GHRH) for induction of ovulation, in combination with human menopausal gonadotrophins. It is, however, still doubtful whether or not growth hormones and/or insulin-like growth factors are mandatory for follicular development and fertility. In this study we describe two women with Laron-type dwarfism who lacked insulin-like growth factors and who had spontaneous pregnancies. We also discuss different natural defects in the production and metabolism of growth hormone and insulin-like growth factors in humans, and the fertility performance of the affected females. It is our assumption that GH and systemic insulin-like growth factors may modulate follicular development, but that they are not necessarily mandatory for ovarian follicular development. PMID- 1939544 TI - Hormonal profiles and follicular growth in cycles with imminent ovarian hyperstimulation. AB - Ovarian hyperstimulation syndrome is a common and serious complication of human menopausal gonadotrophin/human chorionic gonadotrophin treatment. We evaluated the changes in the pituitary and ovarian hormone profiles and ultrasonographic follicular regression in 12 patients in whom human menopausal gonadotrophin was discontinued due to 'imminent' ovarian hyperstimulation. Following discontinuation, three distinct periods were observed: (i) days 1-2, the levels of oestradiol, testosterone and prolactin, and the total number of follicles continued to rise; (ii) days 3-6, the levels of oestradiol, testosterone and prolactin declined sharply and the total number of follicles was reduced significantly, while the large and medium sized follicles continued to increase. Levels of follicle-stimulating hormone and luteinizing hormone gradually declined to reach their lowest levels by days 5-6 and then increased. (iii) Thereafter the number of follicles and steroid output declined to early follicular phase levels. We conclude that discontinuation of human menopausal gonadotrophin and withholding human chorionic gonadotrophin in cycles with laboratory signs of 'imminent' ovarian hyperstimulation syndrome, allows regression of the ovarian ultrasonographic finding and prevents the development of clinical symptoms. However, if rescue of the cycle is attempted, human chorionic gonadotrophin should be given during the first 4 days after discontinuation of stimulation. PMID- 1939546 TI - Transvaginal intratubal embryo transfer: a new treatment of male infertility. AB - Intratubal embryo transfer is a new method in the treatment of human infertility. Following transvaginal sonographic oocyte retrieval, in-vitro fertilization (IVF) is performed and embryos are transferred into the Fallopian tube transvaginally. In comparison with gamete intra-Fallopian transfer (GIFT), 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, embryonic development occurs in the physiological milieu of the oviduct. Transvaginal intratubal embryo transfer was performed in 95 patients with male factor infertility. In 29 cases (31%), a pregnancy was achieved. One abortion, but no ectopic pregnancy was observed. This method combines the advantages of IVF and GIFT and offers a successful procedure for the treatment of infertility. PMID- 1939547 TI - Routine application of partial zona dissection for male factor infertility. AB - Partial zona dissection (PZD) increases the chances of fertilization by improving the access of spermatozoa to the perivitelline space (PVS) helping those spermatozoa unable to penetrate the zona pellucida (ZP) and possibly those poorly able to penetrate the oolemma. Problems arise in assessing semen to decide which parameters might indicate defects of this nature. PZD, by circumventing the ZP, may also increase the rate of polyspermy, especially in infertility where ZP and oolemmal penetration are not defective. Given these drawbacks, we performed PZD as routine treatment for male infertility in 70 in-vitro fertilization cycles. In three different groups, PZD proved to be either effective, ineffective or unnecessary. In the first group of 35 cycles, fertilization was 23% with initial PZD and 33% with PZD reinsemination (36% and 41% polyspermy respectively). No fertilization occurred following conventional insemination (CONV). Four pregnancies occurred in this group. In a second group of 19 cycles, fertilization did not occur with either PZD or CONV. In the final group of 16 cycles, fertilization was similar following both PZD and CONV, but polyspermy was 48% in the PZD category. Transfer of mixed PZD and CONV embryos in this group yielded 10 pregnancies. Assessment of all patient and seminal profiles, and those in an oligozoospermic subcategory, revealed no parameters of relevance to success or failure with PZD. However, one subgroup in the group of total failure to fertilize did have a significantly lower percentage of normal morphology (P less than 0.005), suggesting that degree of teratozoospermia may be a prognosticator of success using PZD. PMID- 1939548 TI - Selective follicular reduction following ovulation induction by exogenous gonadotrophins in polycystic ovarian disease. A new approach to treatment. AB - Seven patients with polycystic ovarian disease (PCO) and having polyfollicular development following ovulation induction by human menopausal gonadotrophin underwent selective follicular reduction by transvaginal ultrasound-guided aspiration of all follicles greater than or equal to 10 mm in diameter leaving two or three preovulatory mature follicles. Twenty-four and 48 h after injection of human chorionic gonadotrophin, the couples had intercourse. Five patients achieved pregnancy in 15 treatment cycles, four in their first cycle after 14 previous unsuccessful stimulation cycles. Four have delivered healthy children: three singletons and one set of twins. One patient spontaneously aborted twins in week 22 of pregnancy. No major complications were encountered. Selective follicular reduction seems to be a possible approach to the treatment of PCO patients having polyfollicular development following ovulation induction. PMID- 1939550 TI - Comparison of transvaginal and transabdominal ultrasound for monitoring follicular development in an in-vitro fertilization programme. AB - Although nowadays most oocyte retrievals for in-vitro fertilization (IVF) are performed using a transvaginal, ultrasound-directed technique, monitoring of follicular development is still often performed via the abdominal route. On the bases of 106 sonographies carried out on 71 patients during ovulation monitoring within an IVF programme, we demonstrated that the number of follicles visualized endovaginally was significantly higher than that visualized by the abdominal route: n = 1124 versus n = 772 respectively, and that their size was significantly greater using the transvaginal approach: 20.8 mm versus 18.8 mm respectively, for the largest follicle. Consequently, if ovulation monitoring is carried out transvaginally, the follicular size criteria on which human chorionic gonadotrophin is administered must be reconsidered. PMID- 1939549 TI - Replacement of frozen-thawed embryos in artificial and natural cycles: a prospective semi-randomized study. AB - This prospective partly-randomized study assessed the relative efficacy of two strategies of patient management for the replacement of frozen-thawed embryos. A luteinizing hormone-releasing hormone (LHRH) agonist was used to induce a temporary hypogonadism in a group of patients who were then prepared for implantation by endometrial priming with hormone replacement therapy (HRT): oral oestradiol valerate and then oestradiol valerate and injections of progesterone. A second group of patients had their frozen-thawed embryos replaced during their natural cycles. Of the 84 patients treated with the LHRH regimen, 80 had embryos replaced and 16 (20%) clinical pregnancies were established. Of the 78 patients treated with natural cycles, 70 had embryos replaced and 14 (20%) achieved clinical pregnancies. There were no statistical differences between the two groups in terms of age, obstetric history, duration of infertility, number of oocytes retrieved and fertilized or the number of embryos frozen following ovarian stimulation in the embryo 'generating' cycle. In terms of pregnancy rates, both protocols were equally effective. However, the LHRH-HRT protocol was of great value in the management of oligomenorrhoeic patients and in establishing standard conditions for implantation in cyclic patients. PMID- 1939551 TI - Diethylstilbestrol-induced mullerian abnormalities, septate uterus, genital tuberculosis and twin pregnancy with term delivery after in-vitro fertilization. AB - We report a case of a twin pregnancy at term obtained after five multiple embryo transfers in a patient who presented diethylstilbestrol (DES)-associated cervical and uterine structural abnormalities, a septate uterus and bilateral tuberculous salpingitis. The suitability of in-vitro fertilization/embryo transfer in DES exposed women is discussed. PMID- 1939552 TI - Endometriosis in pregnant and non-pregnant women at tubal sterilization. AB - The prevalence of endometriosis was investigated in 208 women at the time of laparoscopic tubal sterilization. In 101 women who were in the first trimester of pregnancy, 16% endometriosis was found. In 107 non-pregnant women, 22% endometriosis was detected. Endometriosis in the pregnant women showed more superficial, non-pigmented, gland-like lesions than in the non-pregnant group. In 23% of the endometriotic lesions from pregnant women, no decidualization was found. No special risk factors for developing endometriosis were found. PMID- 1939553 TI - The effect of in-vitro ageing on mouse sperm chromosomes. AB - In-vitro ageing has long been suspected to affect adversely the ability of spermatozoa to fertilize and produce viable zygotes. A comparison of the first cleavage chromosome complement of 824 mouse embryos fertilized with fresh spermatozoa and 656 embryos fertilized with spermatozoa aged for 12, 24 or 48 h is reported herein. The chromosome analysis of first-cleavage embryos allows us to study directly the paternal and maternal chromosome complements which contribute to the embryo. Both chromosome clusters remain separate when an antimitotic agent is used to prevent metaphase synchronization, allowing identification of maternal and paternal chromosomes. We show that after sperm ageing, there is a decrease in the fertilization rate from 75% in the controls to 57.5% (12 h of ageing), 63.5% (24h of ageing) and 4.4% (48 h of ageing). Simultaneously, the level of chromosome structural abnormalities increase from 1.3% in the controls to 16.5% after 12 h of ageing, 18.8% after 24 h of ageing and 59% after 48 h of ageing. The incidence of aneuploidy and polyploidy is not affected by ageing of the spermatozoa. Most of the structural abnormalities are paternal in origin and are presumably induced by the ageing of spermatozoa. PMID- 1939554 TI - Cytogenetic study of human oocytes uncleaved after in-vitro fertilization. AB - Chromosome analysis of oocytes uncleaved after IVF allows the cause of the failure of cleavage to be determined and shows the incidence of chromosome disorders among human oocytes. A total of 198 uncleaved oocytes fixed 40 h after insemination were successfully analysed according to Tarkowski's air-drying method: 78.3% were unfertilized and arrested in metaphase II. Among them, 70% were normal (23,X) and 30% aneuploid (16% were hypohaploid, 14% were hyperhaploid). The incidence of chromosome breaks was 18%. In 12.1% of the oocytes, sperm chromosome condensation appeared premature usually in the G1 phase. This was especially observed in idiopathic infertility (7% of fertilized oocytes versus 2% in tubal infertility cases). In 8.1% of the cases, chromosome analysis showed diploidy which may be interpreted by either an absence of extrusion or a reintrusion of the polar body or by first cleavage failure during mitosis. In 1% of the cases triploidy was observed. Our results show that the main reason for failure of cleavage is related to failure of fertilization (78.3%). However, premature condensation of sperm chromosomes at the G1 phase appears to be quite frequent. This may be involved in the aetiology of some cases of idiopathic infertility. Finally, the high rate of chromosomal disorders (30%) in human oocytes may explain the high rate of chromosomal abnormalities in preimplantation embryos. PMID- 1939555 TI - Presence of a 16 kd protein in human seminal plasma counteracts the effects of the anti-fertility agent, gossypol. AB - Gossypol inhibited lactate dehydrogenase (LDH) noncompetitively in human spermatozoa. The inhibitory effect of gossypol on LDH was cancelled by the addition of human serum albumin, human gamma-globulin, bovine serum albumin or human seminal plasma. Seminal plasma was at least 10 times more effective than the other three proteins, when expressed on a per mg protein basis. Attempts were made to purify the active fraction from human seminal plasma. The purification steps included gel filtration, ammonium sulphate precipitation, centrifugal microconcentration and fast-performance liquid chromatography. A single active protein of Mr = 16,000 was purified to a final yield of 0.18%. The 16 kd protein was not observed in male blood plasma. The protein was found to be heat-stable and leucine-rich (16% of the molecule), and has been designated 'gossact'. The inhibitory effect of gossypol on the LDH reaction was completely blocked by the addition of gossact (5 micrograms/ml); human blood plasma (25 micrograms/ml) and human serum albumin (200 micrograms/ml) were far less potent in this assay. In addition, gossact bound 1.4 mol of gossypol/mol of protein with the dissociation constant (Kd) = 3.06 x 10(-5) M. The role of gossact in the protection of LDH from gossypol is discussed. PMID- 1939557 TI - Ureaplasma in semen and IVF. AB - Ureaplasma urealyticum (U.U.) screening has been systematically performed in tests carried out before IVF cycles. In 42% of the cases (306 couples), at least one partner presented a monomicrobian U.U. infection. U.U. infection of at least one fraction of the split ejaculate was observed in 32% of the cases and found in similar proportions at the prostatic and seminal vesicle levels. The U.U. infected group presented a similar number of cytological abnormalities to the noninfected samples. However, there was a significant reduction in the pregnancy rate after embryo transfer in the infected group whereas U.U. did not alter fertilization parameters, embryo retrieval or pregnancy rates per puncture. The preliminary results of a complementary prospective study (70 couples) point to the likely role of sexually transmitted Ureaplasma at the endometrial level. PMID- 1939556 TI - A follow-up study of sperm preparation for IVF by swim-up in a solution of hyaluronate. AB - Spermatozoa prepared for in-vitro fertilization (IVF) by swim-up in a balanced salt solution containing hyaluronate gave rates of fertilization, cleavage and pregnancy which were not significantly different from those obtained with sperm prepared by swim-up in standard IVF medium followed by centrifugation. However, the content of prostaglandin F2alpha in the final sperm suspension was higher using hyaluronate but this seemed to be of no consequence for IVF. Thus, preparation of normal sperm samples for IVF may be simplified by performing swim up in a balanced salt solution containing hyaluronate. PMID- 1939558 TI - The effects of endotoxins on gametes and preimplantation embryos cultured in vitro. AB - Culture media used for human in-vitro fertilization (IVF) can be contaminated with bacterial endotoxins. All five tested types of commercially available albumin, sometimes used as a protein supplement to IVF media, were shown to contain endotoxins in varying concentrations. Endotoxins are suspected to cause embryo fragmentation and low pregnancy rates in human IVF. However, human sperm viability and the IVF of mouse oocytes and subsequent culture of the zygotes were shown to be unaffected by relatively high endotoxin concentrations. Therefore these techniques cannot be used as quality control assays to detect endotoxins in the IVF culture media. PMID- 1939559 TI - Clinical experience with ultra-rapid freezing of embryos. AB - A modified ultra-rapid freezing technique was introduced in January 1989 in our clinical in-vitro fertilization freezing programme. Thus, we wish to report our 1 1/2 year experience with ultra-rapid freezing as a simple and inexpensive method of routine cryopreservation. Of 181 frozen-thawed embryos, 110 (61%) survived with 50-100% blastomeres intact, and were used in 91 embryo replacements. Nine clinical pregnancies were established including two sets of twins. There was one miscarriage and one ectopic pregnancy. So far, five patients have delivered six normal, healthy infants and two other pregnancies are normally ongoing, including another twin pregnancy. These results were similar to those obtained by the conventional slow freezing method using propanediol. There is no doubt that there is a marked advantage of ultra-rapid freezing when compared to previous methods in terms of cost and time. We therefore believe that more clinical attention should be given to ultra-rapid freezing and it should become increasingly the method of choice for human embryo freezing in IVF programmes. PMID- 1939560 TI - Lack of placental protein 14 production in pregnancy after frozen embryo transfer, down-regulation of anterior pituitary and administration of exogenous oestradiol and progesterone. AB - The circulating levels of placental protein 14 (PP14) and progesterone were measured in three pregnancies resulting from the transfer of cryopreserved embryos. Two of these women had suppressed ovarian activity as a result of pituitary down-regulation with the luteinizing hormone-releasing hormone agonist (buserelin) prior to treatment with exogenous oestradiol and progesterone. After 14 days of oral oestradiol treatment and if the endometrial thickness was greater than 7 mm, progesterone was given intramuscularly for a further 14 days with embryo transfer on the third day of this treatment. On confirmation of pregnancy by human chorionic gonadotrophin analysis, progesterone administration was altered to transvaginal pessaries for maintenance of adequate progesterone levels and endometrial support. In the two women with ovarian suppression, PP14 levels remained below the 2.5th centile of the normal range for pregnancy. In the third pregnancy, embryo transfer was performed 3 days after a spontaneous luteinizing hormone surge in a normal menstrual cycle. In this pregnancy, PP14 levels were within the normal range. Ultrasonic examination confirmed three normal ongoing singleton pregnancies. These results suggest that the majority of PP14 production in normal pregnancy is under ovarian or anterior pituitary control and that the influence of progesterone is of a secondary nature. PMID- 1939561 TI - Uterine activity and decidual prostaglandin production in women in early pregnancy in response to mifepristone with or without indomethacin in vivo. AB - Mifepristone stimulates uterine activity in pregnant women in the first trimester. In-vitro studies have shown that the addition of mifepristone to culture medium increases the ability of decidual cells to generate prostaglandins. In this study, pregnant women of less than 56 days gestation were treated with mifepristone (600 mg) 24, 36 or 48 h prior to surgical termination of pregnancy. Another cohort of women were similarly treated with mifepristone, but also received indomethacin (100 mg b.d.). Control groups, given indomethacin alone (100 mg b.d. for 48 h) or no treatment, were also included. Uterine activity was measured immediately prior to surgical termination of pregnancy and the ability of decidua obtained at operation to generate prostaglandins in culture was measured. Uterine activity was increased in all groups pretreated with mifepristone, an increase which was not prevented by co-administration of indomethacin. In the groups pretreated with mifepristone 36 h previously, the production of prostaglandin F2 alpha (PGF2 alpha) by decidua in vitro was increased. In the group in whom indomethacin was given in addition to mifepristone 36 h prior to the study, there was a marked reduction in the ability of decidua to generate PGF2 alpha. In spite of this suppression, the increase in uterine activity was similar to the group which had not received indomethacin. These results suggest that factors other than an increase in decidual prostaglandin production are responsible for the increase in uterine activity seen following mifepristone administration in vivo. PMID- 1939562 TI - Heat shock protein 88 and Aspergillus infection. AB - Immunoblotting was used to dissect the antibody responses in the sera of 50 patients with proven invasive aspergillosis, 28 patients with suspected invasive aspergillosis, 35 patients with allergic bronchopulmonary aspergillosis, and 10 patients with an aspergilloma. This demonstrated the immunodominance of antigenic bands at 88, 84, 51, and 40 kDa. Monoclonal antibodies against the heat shock protein 90 complexes of Candida albicans and the water mold Achlya ambisexualis identified these four antigenic bands as homologous proteins. Similar antigens have been described in humans, mice, Saccharomyces cerevisiae, chickens, and Drosophila species. The antibody against A. ambisexualis has previously been shown to cross-react with antigens belonging to the human heat shock protein 90 complex. Aspergillus heat shock protein 90 was extracted from the sera of patients with invasive aspergillosis by affinity chromatography. This was done with both a rabbit hyperimmune antiserum raised against an extract of Aspergillus fumigatus NCPF 2109 and a monoclonal antibody against the heat shock protein 90 of C. albicans. In vivo expression of the antigen was demonstrated in an aspergilloma surgically removed from a patient. The role of the antigen as an allergen in allergic bronchopulmonary aspergillosis is also discussed. PMID- 1939563 TI - Proposed interpretive criteria and quality control parameters for testing in vitro susceptibility of Neisseria gonorrhoeae to ciprofloxacin. AB - Ciprofloxacin was subjected to a multilaboratory study designed to determine its in vitro susceptibility criteria for Neisseria gonorrhoeae and its quality control parameters for both agar dilution and disk diffusion susceptibility testing for this species. All clinical isolates were susceptible, i.e., MICs were less than or equal to 0.06 microgram/ml and zones of inhibition were greater than or equal to 36 mm. A resistant category could not be defined, but in vitro selected mutants gave zones of less than or equal to 35 mm, and MICs for these strains were greater than or equal to 0.12 microgram/ml. For quality control of ciprofloxacin agar dilution tests on supplemented GC agar, MICs for Staphylococcus aureus ATCC 29213 ranged from 0.12 to 0.5 microgram/ml. For quality control of 5-micrograms ciprofloxacin disk tests, N. gonorrhoeae ATCC 49226 and S. aureus ATCC 25923 produced acceptable zone diameter ranges of 48 to 58 mm and 22 to 26 mm, respectively. PMID- 1939564 TI - Identification of Toxoplasma gondii infections by BI gene amplification. AB - The diagnosis of toxoplasmosis in congenitally infected children or in immunocompromised patients can be difficult; serology is not reliable, and the diagnosis must be based on the combination of symptomatology and the direct demonstration of the parasite in clinical specimens by microscopy, antigen detection, or inoculation of samples into mice or tissue cultures. These techniques are either insensitive or time-consuming. To determine the value of the polymerase chain reaction (PCR) for the diagnosis of Toxoplasma gondii infections, we compared this technique with conventional detection techniques, such as microscopy, tissue culturing, and mouse inoculation. We were able to detect T. gondii by PCR in clinical specimens and tissue samples that were obtained postmortem from a bone marrow recipient with cerebral toxoplasmosis and from three congenitally infected children. The presence of T. gondii was demonstrated in brain tissue, cerebrospinal fluid, the heart, and skeletal muscle tested fresh or after fixation in Formalin. In only one sample was T. gondii isolated by mouse inoculation but not detected by PCR. Because it is a sensitive, relatively rapid, and specific method and because it can be applied to a variety of different clinical samples, PCR can be considered a valuable additional tool for the identification of T. gondii infections. PMID- 1939565 TI - Characterization of risk factors for Helicobacter pylori infection among men attending a sexually transmitted disease clinic: lack of evidence for sexual transmission. AB - The mechanism of transmission of Helicobacter pylori is unknown. To investigate the role of sexual behavior and demographic factors in the acquisition of H. pylori infection, we evaluated the seroprevalence of antibody to H. pylori in 370 men attending an urban sexually transmitted diseases clinic. Sera from the following three groups were analyzed by enzyme-linked immunosorbent assay for H. pylori-specific immunoglobulin G: 78 human immunodeficiency virus (HIV) seropositive homosexual men, 102 HIV-seronegative homosexual men, and 190 HIV seronegative heterosexual men. Overall, the seroprevalence of H. pylori was 100 of 370 men (27%), with rates of 18% in HIV-seropositive homosexual men and 20% in HIV-seronegative homosexual men versus 35% in heterosexual men (P less than 0.005, chi 2 test). By ethnic group, 21 (12%) of 181 Caucasian men, 40 (41%) of 97 black men, and 37 (43%) of 87 Hispanic men were seropositive (P less than 0.001, chi 2 test). Multivariate analysis revealed that race was associated with H. pylori seropositivity independent of HIV status, sexual preference, or age. There was no relationship between H. pylori seropositivity and the number of lifetime sexual partners or previous sexually transmitted diseases. Three HIV seropositive men with H. pylori immunoglobulin G had essentially identical antibody titers over 8 to 16 months of follow-up. In conclusion, black and Hispanic men have significantly higher H. pylori seroprevalence rates than do Caucasian men, but neither sexual behavior nor HIV infection influences the presence or persistence of H. pylori antibody. Further evaluation of the factors associated with these ethnic differences may lead to a better understanding of H. pylori acquisition and transmission. PMID- 1939566 TI - Heterogeneity, persistence, and distribution of Pseudomonas aeruginosa genotypes in cystic fibrosis patients. AB - A collection of 222 isolates of Pseudomonas aeruginosa was obtained from the respiratory tract of 16 patients with cystic fibrosis over a 4- to 9-month period. Fourteen of these patients were unrelated, while the remaining two were siblings. Isolates were typed by conventional pyocin typing and also by the use of a DNA probe containing 741 bp immediately upstream of the exotoxin A structural gene and the initial 732 bp of the exotoxin A structural gene. By pyocin typing, 69% (11 of 16) of the patients were shown to harbor a single type that persisted in the lung throughout the study. By genotyping (DNA probe typing), all but three patients (13 of 16, 81%) harbored a single persistent genotype in their lungs. Six patients other than the sibling pair (6 of 14, 43%) shared a common genotype in their lungs as judged by DNA probing, and the pyocin type of these isolates was also identical. In four of these six patients, the shared genotype was also the persistent genotype. The sibling pair studied also carried a common genotype in their lungs as indicated by DNA probing, even though the pyocin type of these isolates varied. Results presented suggest that the majority of patients harbor a persistent strain in their lungs and that cross colonization may occur. PMID- 1939567 TI - Amplification of a species-specific DNA fragment of Mycobacterium tuberculosis and its possible use in diagnosis. AB - In recent work, a species-specific Mycobacterium tuberculosis DNA fragment was cloned and sequenced. On the basis of its nucleotide sequence, two oligonucleotides were synthesized and used as primers for polymerase chain reaction (PCR) amplification. A 396-bp fragment was specifically amplified from the M. tuberculosis genome. No amplification was observed from any of 10 different mycobacterial strains, included those belonging to the M. tuberculosis complex. Neither was this fragment amplified from genomes of humans or different species of clinically important bacteria. The PCR product was detected by dot blot hybridization even when as little as 10 fg of purified M. tuberculosis DNA was used. This amplification method was subsequently used to detect and identify bacilli in different clinical samples, such as sputum, urine, and cerebrospinal fluid. A good correlation was observed between the results obtained with the PCR method that we describe and other diagnostic tests currently used. Thus, PCR amplification of this genomic fragment is proposed as a specific, rapid, and sensitive test for the diagnosis of infection with M. tuberculosis. PMID- 1939568 TI - Microbial stabilization of antibiotic-containing urine samples by using the FLORA STAT urine transport system. AB - The FLORA-STAT Urine Transport System (Wadley Biosciences Corp./Lymphokine Partners Ltd., Dallas, Tex.) was evaluated for its efficacy in maintaining organism count and in effectively blocking the bactericidal action of therapeutic antimicrobial agents in urine samples when the urine samples were held at room temperature. Reconstructions with 53 organism-antimicrobial combinations were performed at 0, 4, 8, and 24 h in which the FLORA-STAT system was compared with two boric acid-based systems (Urine C&S Transport Kit [Becton Dickinson VACUTAINER Systems, Rutherford, N.J.]; Sage Urine Collection Kit for Culture [Sage Products, Inc., Cary, Ill.]) and untreated urine. At 24 h, less than 1-log unit changes in organism counts were found in 100, 92, and 10% of the urine samples without antimicrobial agents and in 97, 65, and 16% of the urine samples with antimicrobial agents for FLORA-STAT-treated, boric acid-treated, and untreated urine samples, respectively. The FLORA-STAT system was further evaluated by sending split samples prepared from laboratory-inoculated patient urine samples (57 without and 50 with antimicrobial agents) to four commercial laboratories by using their respective transport devices and procedures. Samples were also sent to a local reference laboratory which provided prompt processing. Each laboratory received independently labeled transport devices containing untreated, FLORA-STAT-treated, and preservative-treated (if provided by the commercial laboratory) samples prepared from the same urine specimen of a patient. Average estimated transport times ranged from 13 to 24 h for the commercial laboratories; the transport time was less than 4 h for the local reference laboratory.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939569 TI - Development of simian immunodeficiency virus isolation, titration, and neutralization assays which use whole blood from rhesus monkeys and an antigen capture enzyme-linked immunosorbent assay. AB - Assays that use rhesus macaque whole blood and an antigen capture enzyme-linked immunosorbent assay for the simian immunodeficiency virus (SIV) p27 core protein were developed for the isolation of SIV from the blood of infected animals, the titration of infectivity of SIV inocula, and the quantitation of virus neutralizing antibodies in serum. These assays required small amounts of whole blood, were adaptable to a microtiter format, and used substrates mainly of rhesus macaque origin. PMID- 1939570 TI - Direct identification of bacterial isolates in blood cultures by using a DNA probe. AB - This study involved the rapid, direct identification of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, Enterococcus sp., and Streptococcus agalactiae from positive blood culture bottles (BACTEC, Johnston Laboratories, Inc.) by using the AccuProbe (Gen-Probe, San Diego, Calif.) culture confirmation test. This method uses a chemiluminescent DNA probe that detects the rRNA of the target organisms. The manufacturer's instructions were modified to use a pellet of bacteria made directly from positive blood culture broth rather than a colony from an agar plate. Two separate procedures of selective centrifugation were employed in order to obtain the pellet. The first utilized a routine clinical centrifuge and a large volume of broth (10 to 12 ml) from the blood culture bottle. The second method used a microcentrifuge and less volume (1 to 1.5 ml). A total of 196 clinical specimens taken directly from positive blood culture broths were correctly identified by AccuProbe from pellets made by using the clinical centrifuge technique, while 166 clinical specimens used as negative controls failed to show hybridization. The microcentrifuge technique for obtaining pellets was performed on 105 patient specimens, and all were correctly identified. When combined with the microcentrifuge technique for pellet preparation, the AccuProbe test has several advantages: (i) direct identification of bacteria from blood culture broths, (ii) rapid turn-around time (30 min), (iii) simplicity of the procedure, and (iv) relative low cost. PMID- 1939571 TI - Evaluation of the E test for susceptibility testing of anaerobic bacteria. AB - The susceptibilities of 105 clinical isolates of anaerobic bacteria were determined by a new method, the E test (AB Biodisk, Solna, Sweden), and were compared with the MICs for these organisms obtained by the reference agar dilution method by using supplemented brucella and Wilkins-Chalgren agars. The E test is a plastic strip with a predefined antibiotic gradient immobilized on one side and a MIC interpretive scale printed on the other side. Strips with cefoxitin, cefotaxime, imipenem, penicillin, metronidazole, and clindamycin were used in this study. A suspension of the test strain equal to the visual turbidity of a no. 0.5 McFarland standard was prepared and swabbed onto a 150-mm-diameter plate. The strips were applied in a radial fashion, and the plates were incubated under anaerobic conditions. After growth had occurred, an ellipse of inhibition was seen around each strip. At the point of intersection of the ellipse with the strip, the MIC was read from the interpretive scale. For most antibiotic-organism combinations, the ellipse was clear and the endpoint was sharp. The E-test MICs were interpreted after overnight and 48-h incubation for 58 of the strains. After overnight incubation, 87% of the E-test MICs were within 1 dilution of the agar dilution MICs, and 98% were within 2 dilutions. After 48 h of incubation, agreement was 86 and 97% respectively. E-test MICs obtained for the Bacteroides fragilis group after overnight incubation were more comparable than those obtained after 48 h of incubation to agar dilution MICs determined at 48 h for all drugs except clindamycin. On brucella agar, there was a 2% categorical discrepancy rate between the E-test MICs and agar dilution MICs, which occurred mostly with cefoxitin. The E test is easy to perform and read, is suitable for all anaerobes, can be used to test single patient isolates as needed, and offers the laboratory a reliable method for susceptibility testing of anaerobic bacteria. PMID- 1939572 TI - Identification of two new antigenic subgroups within the genus Mobiluncus. AB - Classifications of 48 atypical clinical isolates of Mobiluncus spp. were determined on the basis of biochemical reactions, morphology, antigenic profiles, and DNA hybridization studies. Two new subgroups with unique antigenic profiles are described. Like typical Mobiluncus species, the antigenic variant of M. mulieris is associated with bacterial vaginosis. The atypical isolates of M. curtisii were frequently recovered from women with normal vaginal flora and were also recovered from sterile body sites. These isolates may be incorrectly identified if current biochemical and morphological criteria are used for identification. Gram stain morphology, however, correctly identifies these isolates to the species level. The characterization of these atypical isolates has important implications for future investigations in which serological methods are used for diagnosis, epidemiology, and determination of pathogenicity of Mobiluncus spp. PMID- 1939573 TI - Detection of rubella virus immunoglobulin G (IgG) and IgM antibodies in whole blood on Whatman paper: comparison with detection in sera. AB - We compared detection of rubella virus hemagglutination inhibition (HI) antibody and rubella virus-specific immunoglobulin M (IgM) in dried whole blood spotted onto Whatman filter paper and serum samples, both of which were obtained from the same subject by venipuncture. Of 1,000 paired serum samples obtained to study HI antibodies, 807 dried blood samples had HI titers identical to those of the corresponding serum samples, and 193 dried blood samples showed 1 dilution difference. Storage of dried blood at room temperature for 28 days did not affect the HI antibodies. In a study of specific IgM by a solid-phase immunosorbent HI test done with blood from healthy subjects and patients with rubella, the result of the presence, positive or negative, of specific IgM from both blood sample sources corresponded when the dried blood samples were stored at room temperature from 5 h to 38 days. This study demonstrated that the use of Whatman filter paper as a transport medium for blood samples for the determination of rubella virus immunity and the diagnosis of rubella virus infection is possible. PMID- 1939574 TI - Evaluation of the L-CLONE Legionella pneumophila Serogroup 1 Urine Antigen Latex Test. AB - The purpose of this study was to evaluate the L-CLONE Legionella pneumophila Serogroup 1 Urine Antigen Latex Test (Access Medical Systems, Inc., Branford, Conn.) for detection of Legionella antigen in urine. A total of 481 frozen urine samples previously tested by an in-house solid-phase radioimmunoassay (RIA) was thawed and retested by using L-CLONE. Included in this sample were 140 RIA positive samples from culture-positive or serologically confirmed cases of legionellosis and 341 RIA-negative samples from patients with non-Legionella respiratory disease or bacteriuria. The original RIA test result was accepted as the true value. L-CLONE correctly identified 76 of 140 (54%) known positive samples. False-negative results could not be attributed to a low Legionella antigen concentration or to a Legionella antigen subgroup. L-CLONE correctly identified 252 of 341 (74%) known negative samples. False-positive results were experienced in all groups of negative samples, regardless of the patients' underlying diseases. A total of 141 fresh urine samples was tested; all were Legionella antigen negative by RIA. L-CLONE provided 86% specificity. The sensitivity of the L-CLONE in testing fresh urine samples could not be evaluated because of the lack of Legionella antigen RIA-positive samples. PMID- 1939575 TI - Diagnostic application of polymerase chain reaction for detection of Ehrlichia risticii in equine monocytic ehrlichiosis (Potomac horse fever). AB - Genomic amplification by the polymerase chain reaction (PCR) was used to identify a unique genomic sequence of Ehrlichia risticii directly in DNA isolated from peripheral-blood buffy coat cells of E. risticii-infected horses (Potomac horse fever) and from infected cell cultures. A specific primer pair, selected from a cloned, species-specific, 1-kb DNA fragment of the E. risticii genome as a template, was used for the amplification of the target DNA of 247 bp. The optimal number of 40 PCR cycles, determined by analyzing an amplification profile obtained with a constant Taq polymerase concentration, was used to achieve maximum amplification of the E. risticii DNA segment. Efficient amplification of target DNA was achieved with specimens processed by either the phenol extraction or rapid lysis method. The specificity of the amplified DNA product was confirmed by the proper size (247 bp) and appropriate restriction enzyme cleavage pattern of the amplified target DNA, as well as by the specific hybridization signal obtained by using a PCR-amplified 185-bp internal DNA probe. A 10(5)- to 10(6) fold amplification of target DNA, which allowed detection of E. risticii from as few as two to three infected cells in culture and from a very small volume of buffy coat cells from infected horses, was achieved. This PCR amplification procedure was found to be highly specific and sensitive for the detection of E. risticii for the study of Potomac horse fever. PMID- 1939576 TI - Differences in genomic DNA sequences between pathogenic and nonpathogenic isolates of Entamoeba histolytica identified by polymerase chain reaction. AB - A lambda gt11 cDNA library was constructed from the poly(A)+ RNA of trophozoites of Entamoeba histolytica HM-1:IMSS strain. The library was immunologically screened with monoclonal antibody 4G6, which is specific for the 30,000-Mr antigen of pathogenic isolates. A 0.7-kb clone was isolated, and its nucleotide sequence was determined. To examine whether this gene was specific for pathogenic isolates, a polymerase chain reaction was performed by using four sets of primers and the genomic DNA of pathogenic and nonpathogenic isolates as templates. Amplified DNAs were detected not only in pathogenic isolates but also in nonpathogenic isolates. However, when sequences of amplified DNA of these isolates were compared, minor differences were observed. By considering the presence or absence of recognition sites of some endonucleases, it was possible to distinguish between the pathogenic and nonpathogenic isolates. When various isolates with different zymodemes were examined by polymerase chain reaction and enzyme digestion, the results of typing were entirely in accord with those of zymodeme analysis. These results indicate that there is dimorphism in the genomic DNA coding the 30,000-Mr antigen of E. histolytica and that the combined use of the polymerase chain reaction and enzyme digestion is a useful strategy for identification of species and determination of pathogenicity. PMID- 1939577 TI - Identification of methicillin-resistant strains of staphylococci by polymerase chain reaction. AB - A simple and reliable method using a polymerase chain reaction (PCR) was devised to identify methicillin-resistant staphylococci. By using lysates of the strain to be tested as templates and 22-mer oligonucleotides as primers, a 533-bp region of mecA, the structural gene of a low-affinity penicillin-binding protein (PBP 2'), was amplified by PCR and detected by agarose gel electrophoresis. Results obtained by this method were compared with those obtained by broth microdilution MIC determination for 210 and 100 clinical isolates of Staphylococcus aureus and coagulase-negative staphylococci, respectively. Of 99 mecA-negative S. aureus isolates, 100% of the strains were methicillin susceptible and 98% of the strains were oxacillin susceptible. Three strains (3%) of 111 mecA-positive S. aureus isolates exhibited almost the same susceptibility to beta-lactams as the mecA negative ones and did not produce detectable amounts of PBP 2' despite the presence of the mecA gene. One of them yielded typically methicillin-resistant variants at a low frequency with concomitant recovery of PBP 2' production. The mecA gene was also found in coagulase-negative Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus sciuri, Staphylococcus saprophyticus, and Staphylococcus caprae and conferred resistance on most of the bacteria. PMID- 1939578 TI - Clinical comparison of the resin-containing BACTEC 26 Plus and the Isolator 10 blood culturing systems. AB - The new resin-containing BACTEC 26 Plus blood culturing system (Becton Dickinson Diagnostic Instrument Systems, Towson, Md.) was compared with the Isolator 10 system (Wampole Laboratories, Cranbury, N.J.). Blood samples were drawn by syringe, and equal 10-ml volumes were evaluated in each blood culture system by the recommended methods. Both systems were incubated aerobically with 5% CO2. Of 11,506 acceptable study specimens, 1,788 aerobic isolates were recovered. Overall, recoveries was similar for the two systems, with 626 bacteria or fungi recovered in the BACTEC 26 Plus system only, 499 recovered in the Isolator system only, and 663 recovered in both systems. Of 345 gram-negative rods, 62 grew in the BACTEC system only and 109 grew in the Isolator system only (P less than 0.001). Thirty-three of these Isolator-only gram-negative organisms were Acinetobacter spp. Of 209 yeasts, 38 grew in BACTEC only and 81 grew in Isolator only (P less than 0.001). Of 200 streptococci and enterococci, 98 were recovered in BACTEC only and 26 grew in Isolator only (P less than 0.001). Two hundred twenty-eight independent episodes of gram-negative rod bacteremia occurred. Isolator was the first system positive in 59 of 197 episodes, compared with 45 of 197 for BACTEC when Acinetobacter episodes were excluded. Times to detection were similar for the two systems. High colony counts correlated with repeat positive blood cultures. Isolator and BACTEC had similar overall recoveries, with individual merits and deficiencies for both systems. The additional quantitative information derived from Isolator had utility in our institution. PMID- 1939579 TI - Immunodot detection of Escherichia coli heat-stable enterotoxin b by using enhanced chemiluminescence reaction. AB - An indirect immunodot assay with rabbit antibodies raised against purified heat stable enterotoxin type b (STb) and with a Western blotting (immunoblotting) detection system (ECL; Amersham International plc, Amersham, United Kingdom) was developed for the detection of STb toxin. Culture supernatants of 62 Escherichia coli isolates from pigs with diarrhea were blotted onto nitrocellulose and incubated with anti-STb serum. The chemiluminescence produced by the action of horseradish peroxidase with luminol and H2O2 was recorded by exposure of X-ray film. Over 90% correlation was observed between the rat or pig intestinal ligated loop assay and a radioactive DNA probe and the ECL immunodot assay for the detection of STb. In addition, using this new and sensitive technique, we could detect STb in the feces of a newborn pig inoculated with an STb-producing E. coli strain. Detection of STb-producing E. coli in pigs with diarrhea will be greatly facilitated by the use of this convenient and rapid diagnostic assay. PMID- 1939580 TI - Synthetic peptide-based immunoassays for distinguishing between human T-cell lymphotropic virus type I and type II infections in seropositive individuals. AB - Until now, serologic tests that distinguish the closely related human T-cell lymphotropic virus types I (HTLV-I) and II (HTLV-II) infections have not been available. Synthetic peptide assays, employing peptides derived from the core and envelope proteins of HTLV-I and HTLV-II (SynthEIA and Select-HTLV tests), were evaluated for the ability to serologically discriminate HTLV-I and HTLV-II infections. Of 32 HTLV-I- and 57 HTLV-II-positive serum specimens from individuals whose infections were confirmed by polymerase chain reaction, the SynthEIA test categorized 29 (91%) as HTLV-I and 50 (88%) as HTLV-II, and 10 (11%) were nontypeable. In contrast, the Select-HTLV test categorized 32 (100%) as HTLV-I and 55 (96%) as HTLV-II, and 2 (2%) were nontypeable. The specificity of both the assays in seropositive serum specimens was 100% in that none of the specimens were incorrectly classified. Additional serum specimens obtained from clinically diseased patients from the United States (n = 8) and asymptomatic carriers and patients from Japan (an endemic population for HTLV-I; n = 40) were categorized as HTLV-I by at least one of the assays, while serum specimens from Guaymi Indians from Panama (an endemic population for HTLV-II; n = 13) were categorized as HTLV-II. Thus, peptide enzyme immunoassays appear to represent a simple technique employing chemically synthesized antigens for discrimination between antibodies of HTLV-I and HTLV-II. PMID- 1939581 TI - Immunomagnetic separation and DNA hybridization for detection of enterotoxigenic Escherichia coli in a piglet model. AB - Enterotoxigenic Escherichia coli (ETEC) strains were detected by stool blot hybridization assays using different oligonucleotide probes for the colonization fimbrial antigen F4, heat-stable enterotoxin I (ST I), and heat-labile enterotoxin (LT I) genes. Forty-eight fecal samples and seven samples of intestinal content from ETEC-challenged newborn piglets were processed in two ways: (i) by direct inoculation of bacterial suspension onto nylon membranes overlaying blood agar and (ii) by immunomagnetic enrichment of F4+ ETEC using magnetic beads coated with F4 monoclonal antibodies before inoculation onto nylon membranes. In samples obtained from nondiarrheic piglets pre- and postchallenge, E. coli genes for F4, ST I, and LT I could be detected only after immunomagnetic enrichment. No difference between the two methods in detection of these E. coli genes was observed when stool blots from diarrheic piglets were examined. By using magnetic separation, it was easy to decrease background bacterial flora, intestinal cells, and fecal debris and thus produce purer specimens. The method evaluated in this animal model appeared simple and quick and increased the sensitivity of detection of ETEC strains 100-fold compared with the direct stool blot hybridization assays. Prior bacterial isolation and identification were not necessary. PMID- 1939582 TI - Use of chemotaxonomy as an aid to differentiate among Capnocytophaga species, CDC group DF-3, and aerotolerant strains of Leptotrichia buccalis. AB - Four strains of fastidious gram-negative rods, thought to be Capnocytophaga species (formerly CDC group DF-1 or Bacteroides ochraceus) or CDC group DF-3 on the basis of conventional phenotypic criteria, were also analyzed for cellular fatty acid (CFA) composition. It was found that the CFA compositions of these strains were qualitatively incorrect for those taxa. Subsequently, it was determined that all four bacteria were in fact aerotolerant strains of Leptotrichia buccalis, based on biochemical reactions, CFA composition, and lactic acid as the major end product of glucose fermentation. It is recommended that, in addition to conventional cultural and biochemical criteria, all strains of Capnocytophaga or CDC group DF-3 should also be tested for metabolic end products of fermentation and CFA composition as essential adjuncts for identification. PMID- 1939583 TI - Advantages of a human immunodeficiency virus type 1 (HIV-1) persistently infected HeLa T4+ cell line for HIV-1 indirect immunofluorescence serology. AB - A HeLa T4+ cell line persistently infected with human immunodeficiency virus type 1 (HIV-1) was used in an indirect immunofluorescent antibody assay (IFA) system to explore its potential suitability as an alternative source of viral antigen for confirmatory IFA in HIV serology. In a study of 121 serum samples chosen because they were reactive on repeat examination by enzyme immunoassay but nonspecific by IFA by using HIV-1-infected H9 cells (H9 IFA) or gave discrepant results by enzyme immunoassay and H9 IFA, the specificity and sensitivity of the HeLa T4+ IFA were comparable to those of Western blot (immunoblot), and identification of the true positive samples among these discrepant or nonspecific samples by HeLa T4+ IFA was approximately twice that by H9 IFA. The primary advantages of using the HeLa cell line rather than lymphoid cell lines in IFA are that cells can be grown as a monolayer and that the individual cells are much larger. The cell membrane, cytoplasm, and nucleus are easily discernible; this allows specific and nonspecific staining to be distinguished. At least eight different nonspecific nuclear and cytoplasmic staining patterns were identified in this study by using T4+ cells. PMID- 1939584 TI - Comparison of five commercial enzyme-linked immunosorbent assays and Western immunoblotting for human immunodeficiency virus antibody detection in serum samples from Central Africa. AB - Detection by five different enzyme-linked immunosorbent assays (ELISAs) of antibody to human immunodeficiency virus (HIV) in sera from three Zairian populations consisting of 1,998 individuals with various risks for HIV infection was evaluated. Sera that were reactive by at least one assay and 10% of the nonreactive serum samples were analyzed by Western blot (immunoblot) by using U.S. Public Health Service interpretation criteria. Sera which were positive by ELISA for detection of antibody to HIV-1 and HIV-2 and negative or indeterminate by HIV-1 Western blot were also analyzed by HIV-2 Western blot. Overall, 443 (22.2%) serum specimens were HIV-1 Western blot positive, 390 (19.5%) had indeterminate HIV-1 Western blot patterns, and no samples were HIV-2 Western blot positive. The sensitivity of the ELISAs ranged from 97.5 to 99.8%, and the specificity ranged from 51.7 to 98.4%. By population group, the negative predictive value ranged from 97.1 to 100%, in contrast to the positive predictive value, which varied from 6.6 to 100%. Follow-up results for sera which were indeterminate for antibody to HIV-1 documented only four seroconversions (6.0%) among 67 individuals at high risk for HIV-1 infection and no seroconversions among 202 individuals at relatively low risk for HIV-1 infection. This study demonstrates the importance of evaluating commercial ELISAs with sera from appropriate geographical regions in order to select the most cost-effective and practical assay for use in that region. Furthermore, the high frequency of indeterminate Western blots for African sera emphasizes the continual need for improved confirmatory assays and interpretation criteria. PMID- 1939586 TI - Platelia-Toxo IgA, a new kit for early diagnosis of congenital toxoplasmosis by detection of anti-P30 immunoglobulin A antibodies. AB - With the aim of achieving earlier diagnosis of congenital toxoplasmosis, anti-P30 immunoglobulin A (IgA) antibodies were assayed by using a Platelia-Toxo IgA kit with samples from 72 children born to mothers who seroconverted during pregnancy. A total of 148 serum samples and 1 cerebrospinal fluid samples were from 23 congenitally infected children (2 serum samples were collected from fetuses), and 74 serum samples were from 49 uninfected children. Among the 23 infected children, anti-P30 IgA antibodies were present in all infants either at birth or in the following weeks, whereas anti-P30 IgM antibodies were present in 13 from the 23 infected children either at birth or in the following weeks. Serum samples collected in utero from two infected children were also tested. One of these samples was positive for both anti-P30 IgA and anti-P30 IgM antibodies, whereas both children were negative at birth for these antibodies. Neither anti-P30 IgA nor anti-P30 IgM antibodies were detected in 47 of 49 uninfected children. These results suggest that detection of anti-P30 IgA antibodies by the Platelia-Toxo IgA kit is a very effective method for early diagnosis of congenital toxoplasma infection. PMID- 1939585 TI - Serology and leprosy: immunoassays comparing immunoglobulin G antibody responses to 28- and 30-kilodalton proteins purified from Mycobacterium bovis BCG. AB - Two major proteins from Mycobacterium bovis BCG culture filtrates with molecular masses of 28 kDa (P28) and 30 kDa (P30), identified as components of the BCG 85 complex, were purified and used in enzyme-linked immunosorbent assays (ELISAs) for the determination of specific immunoglobulin G (IgG) levels in patients with leprosy or tuberculosis or with exposure to these diseases. High reactivity to both antigens was observed with sera from lepromatous leprosy patients, whereas antibody levels in sera from paucibacillary leprosy patients were not significantly different from those in sera from healthy individuals from an area in which leprosy is endemic. High IgG responses were also found in some contacts of lepromatous leprosy patients. A comparison of the levels of anti-P28 and anti P30 within the multibacillary leprosy patient group showed much higher IgG reactivity to P28 than to P30, suggesting that the antibody response of lepromatous patients is directed predominantly against the 28-kDa protein. A high degree of correlation in values of ELISAs based on P28 and on the phenolic glycolipid of Mycobacterium leprae was observed in all groups analyzed. The potential use of an assay based on the 28-kDa protein to selectively distinguish individuals destined to develop multibacillary leprosy is discussed, as also is the likelihood that the 28-kDa-30-kDa complex, part of the fibronectin-binding family, is an important component of M. leprae. PMID- 1939587 TI - Evaluation of the MicroScan Rapid Yeast Identification panel. AB - The MicroScan Rapid Yeast Identification (RYI) panel is a 4-h microdilution system for identification of clinical yeastlike isolates. Its accuracy was evaluated by using 357 isolates encompassing 11 genera and 30 species. The RYI panel identifications were compared with those obtained by the API 20C system assisted with morphological characterization on cornmeal-Tween 80 agar. The panels were read both visually and with the AutoScan-4, a computer-controlled microplate reader. Both the RYI panel and the API 20C system correctly identified 78% of the strains within 4 and 72 h, respectively, with no additional tests. Supplementary tests recommended by the manufacturers made it possible to identify up to 96.6% (AutoScan-4) and 98.9% (API 20C) of the strains. The accuracy of the RYI panel was 99.5% with common strains and 92.1% with less common strains. The RYI panel misidentified 10 or 12 strains and failed to identify 2 or 3 strains, depending on whether it was read with the AutoScan-4 or visually. Errors occurred with one strain of Torulopsis glabrata and the less common yeasts T. candida, Candida lusitaniae, C. lambica, C. rugosa, C. stellatoidea, Cryptococcus albidus, C. laurentii, and C. uniguttulatus. Overall, the RYI panel appears to be a reliable system for identification of the more common clinical yeast isolates. PMID- 1939588 TI - Enterosistem 18-R: description and comparative evaluation with conventional methods for identification of members of the family Enterobacteriaceae. AB - The efficiency and accuracy of Enterosistem 18-R (Liofilchem s.r.l., Roseto degli Abruzzi, Teramo, Italy) were compared with those of conventional biochemical methods to identify 360 members (38 species) of the family Enterobacteriaceae. Overall, 329 strains (91.3%) were correctly identified (percentage of identification, greater than or equal to 90.0), with 37 (11.2%) requiring additional tests for complete identification. For 11 isolates (3.1%), Enterosistem 18-R gave only genus identifications, and for 14 (3.9%), the strains did not correspond to any key in the codebook and could not be identified by the manufacturer's computer service. Only six isolates (1.7%) were misidentified. The new system accurately identified common and several newly described isolates of the family Enterobacteriaceae, such as Enterobacter gergoviae, Providencia rustigianii, Serratia odorifera, and Serratia rubidaea. The system is highly reproducible, simple to perform, easy to handle, and inexpensive. With adjustments in supplementary code numbers for some strains, Enterosistem 18-R is a suitable alternative for identification of members of the Enterobacteriaceae in clinical laboratories. PMID- 1939589 TI - Tests for detecting degradation of gelatin: comparison of five methods. AB - Five methods for detecting degradation of gelatin by bacteria were compared. These were liquefaction in nutrient broth, hydrolysis in nutrient agar, hydrolysis of charcoal gelatin strips, degradation of the gelatin on strips of photographic film, and alkalinization of gelatin agar. Degradation of photographic film is a rapid and convenient method but, like hydrolysis of gelatin in broth and in agar, may fail to detect weakly positive strains of bacteria. Alkalinization of gelatin in an agar medium is a convenient and sensitive method to detect degradation of gelatin, particularly by Pseudomonas fluorescens, but this method may not be applicable to some species. PMID- 1939590 TI - Comparison of preservation methods for enterotoxigenic Escherichia coli producing heat-labile enterotoxin. AB - Ten strains of enterotoxigenic Escherichia coli producing heat-labile enterotoxin (LT) were preserved under 12 different conditions. After 1 month, 9 months, and 3 years of preservation, the cultures were recovered and examined for LT production. Preservation of the cultures on Dorset Egg Medium at 4 degrees C and preservation by freezing the cell suspensions in tryptic soy broth with 20% glycerol were found to be suitable preservation methods; all strains were alive for 3 years and had a minimum loss of LT production. PMID- 1939591 TI - Superiority of methylprednisolone over dexamethasone for induction of Pneumocystis carinii infection in rats. AB - Because of difficulties in in vitro cultivation, the basic Pneumocystis carinii studies have been carried out on animal models, mainly on rodents immunosuppressed by corticosteroids. Commonly used dexamethasone and methylprednisolone procedures were evaluated. The intensity of infection in rats was statistically significantly higher after 9 weeks' immunosuppression with methylprednisolone than with dexamethasone. PMID- 1939592 TI - Novel plasmid combinations in Haemophilus ducreyi isolates from Thailand. AB - Thirty isolates of Haemophilus ducreyi collected in Thailand in 1984 were characterized by plasmid content. Three novel plasmids with estimated molecular masses of 1.8, 2.6, and 2.8 MDa were observed in 29 isolates, in addition to the 3.2-, 5.7-, and 7.0-MDa beta-lactamase and 4.4-MDa sulfonamide resistance plasmids. At least three of the seven plasmids were observed in each of the 29 isolates. The number and diversity of plasmids observed in these isolates of H. ducreyi distinguish them from strains previously described. PMID- 1939593 TI - Vancomycin susceptibility and identification of motile enterococci. AB - Thirty-seven clinical isolates of Enterococcus gallinarum and Enterococcus casseliflavus and three type or reference strains of the species were studied with respect to vancomycin susceptibility and key identification characteristics. With the exception of one clinical isolate of E. casseliflavus (MIC, 4 micrograms/ml), MICs of vancomycin were 8 to 32 micrograms/ml. The type strain of E. gallinarum, NCDO 2313, and five of the clinical isolates had similar penicillin-binding protein profiles and shared 90 to 100% DNA homology. Two isolates, identified as E. gallinarum by conventional tests, were shown to be non pigment-producing E. casseliflavus on the basis of penicillin-binding protein profile and DNA homology. The type and reference strains of E. casseliflavus, ATCC 25788 and ATCC 25789, were nonmotile in our experiments. However, both shared 65 to 100% DNA homology with each other and with five clinical isolates of E. casseliflavus. These data suggest that the MICs of vancomycin observed for strains of E. gallinarum and E. casseliflavus are higher than those usually associated with other enterococci and may be a common property of these species. Additionally, pigment production and motility may occasionally be misleading criteria for definitive identification of these organisms. PMID- 1939594 TI - Identification of related DNA sequences in Borrelia burgdorferi and two strains of Leptospira interrogans by using polymerase chain reaction. AB - The suitability of a polymerase chain reaction assay for Borrelia burgdorferi in epidemiological studies of infected tick populations was evaluated by using 28 strains of Leptospira interrogans and lysates of fixed adult Ixodes tick tissues. Two false positives representing leptospires were differentiated from B. burgdorferi by using an oligonucleotide probe. PMID- 1939596 TI - Detection and differentiation of antibodies to human T-cell lymphotropic virus types I and II by the immunofluorescence method. AB - We compared the sensitivities of the prototype human T-cell lymphotropic virus type I (HTLV-I)- and HTLV-II-transformed cell lines, MT2 and Mo-T, with that of an HTLV-II-infected cell line, clone 19, established in our laboratory, in the immunofluorescence (IF) test for detection of antibody to HTLV-I and HTLV-II. In addition, IF antibody titers with the three antigens were determined, and the results were compared with HTLV-I and HTLV-II typing by polymerase chain reaction (PCR). The MT2 cell line was more sensitive than the two HTLV-II cell lines for detecting HTLV-I antibody by IF, and clone 19 was more sensitive than Mo-T or MT2 for measuring HTLV-II antibody. In the titration study, the antigen that gave the highest titer correlated completely with the HTLV type determined by PCR, indicating that the relatively simple IF titration method can be used for differentiating HTLV-I and HTLV-II antibody in sera and plasmas. PMID- 1939595 TI - Convenient agarose medium for simultaneous determination of the low-calcium response and Congo red binding by virulent strains of Yersinia enterocolitica. AB - A simple, efficient method for identification and differentiation of Yersinia enterocolitica containing virulent plasmid-bearing clones is described. The method is based on temperature of incubation and the low calcium response of the organism in an agarose Congo red medium. PMID- 1939597 TI - Chemical characterization of clinical isolates which are similar to CDC group DF 3 bacteria. AB - Six clinical isolates, taken from blood or wounds, that had biochemical characteristics most similar to Centers for Disease Control group DF-3 bacteria were examined for cellular fatty acid composition and isoprenoid quinone content to evaluate their chemical relatedness to known bacterial species and groups. The fatty acids were liberated from whole cells by base hydrolysis, methylated, and analyzed by capillary gas-liquid chromatography. The isoprenoid quinones were extracted from lyophilized whole cells and analyzed by reverse-phase high performance liquid chromatography. All six strains, which were designated group DF-3-like, possessed a distinct fatty acid profile that was characterized by large amounts (greater than 20%) of 13-methyltetradecanoate (i-C15:0) and 12 methyltetradecanoate (a-C15:0), moderate amounts of saturated branched-chain 13 carbon acids (i-C13:0 and a-C13:0) and hexadecanoate (n-C16:0), and small to moderate amounts of both branched- and straight-chain hydroxy acids (i-3-OH C15:0, 3-OH-C16:0, i-3-OH-C17:0, and 2-OH-C17:0). This fatty acid profile was unique compared with the profiles of group DF-3 and other bacteria we have previously tested and is useful for the rapid identification of group DF-3-like isolates. The isoprenoid quinone content of four group DF-3-like strains was similar, with ubiquinone-9 (Q-9) and Q-10 as their major quinones, while the other two group DF-3-like strains contained Q-7 as their major quinones, with smaller amounts of Q-8 and Q-9. PMID- 1939598 TI - Use of Rambach Propylene Glycol Containing Agar for identification of Salmonella spp. AB - When grown on Rambach Propylene Glycol Containing Agar (Rambach agar), 216 of 230 (93.9%) Salmonella organisms isolated from patients and 54 of 62 (87.1%) Salmonella stock cultures produced a crimson-colored growth. Of the 14 clinical Salmonella isolates which displayed colors other than crimson, 8 were Salmonella typhi, 2 were Salmonella paratyphi A, and 4 belonged to other commonly isolated serotypes. All eight Salmonella stock cultures which failed to produce a crimson color belonged to rarely isolated serotypes. In contrast, of 83 non-Salmonella stock cultures distributed among 29 bacterial species, none produced a crimson color. These results suggest that while Rambach agar cannot preidentify S. typhi and S. paratyphi A, the medium can be used for the presumptive identification and can assist in the definitive identification of the overwhelming majority of Salmonella isolates. PMID- 1939599 TI - Detection of salmonellae by using Rambach agar and by a C8 esterase spot test. AB - In food microbiology, Rambach agar facilitates the differentiation of non-typhi Salmonella through a specific red pigmentation of the colonies. The usefulness of Rambach agar was examined relative to its usefulness to the field of clinical microbiology. Of 170 non-typhi Salmonella strains, 92 and 97% gave bright red colonies after 24 and 48 h of incubation, respectively, while 100% of 112 other members of the family Enterobacteriaceae were of a different color (blue, green, beige, or colorless). Red colonies were also found with five of five Acinetobacter isolates and one of three Pseudomonas isolates. To further detect Salmonella typhi and the rare beige or colorless colonies atypical of Salmonella isolates, a C8 esterase detection spot test was carried out. With UV light, that test revealed fluorescent colonies for all Salmonella isolates tested. PMID- 1939600 TI - Amino acid sequences of myosin essential and regulatory light chains from two clam species: comparison with other molluscan myosin light chains. AB - We have determined the amino acid sequences of the essential light chains (ELC) and regulatory light chains (RLC) of myosin from two species of clam, Mercenaria mercenaria and Macrocallista nimbosa, using protein chemistry methods. The N termini of all four proteins were blocked, and sequencing was carried out on various chemically and enzymatically produced peptide fragments. Cleavage of either Mercenaria RLC (MRLC) or Macrocallista RLC (VLC) at its 3 Arg yielded four peptides, three of which could not be sequenced directly, due to an N-terminal blocking group and 2 Arg-Gln bonds in these proteins. The fourth peptide was partially and specifically cleaved at an unusually reactive residue, Met-64, which is invariant in all known RLC sequences. A comparison of all available molluscan ELC and RLC sequences was carried out in search of clues to functionally important features of these proteins in muscles which are regulated by a Ca(2+)-sensitive myosin. By analogy with other RLCs, VRLC and MRLC may be phosphorylated at Ser-11 by an endogenous kinase. All myosin light chains, like troponin C and calmodulin, contain four homologous regions, I to IV, each of which contains a twelve-residue potential Ca(2+)-binding loop flanked on either side by a pair of helices. All RLCs, including those from Ca(2+)-insensitive myosins, contain a divalent cation-binding site in region I. Clam and other molluscan ELCs contain a single Ca(2+)-binding site in region III. This site is present only in the ELCs of myosins that are regulated by direct binding of Ca2+. The ELC site III is likely to play a key role in the regulation of molluscan muscle contraction. PMID- 1939601 TI - Fish myosin alkali light chains originate from two different genes. AB - We have determined the amino acid sequences of mullet white skeletal muscle myosin alkali light chains, LC1 and LC3. These are the first available fish myosin sequences. There are 29 differences between the mullet LC1 and LC3 sequences, spread throughout all regions of their polypeptide chains, leading us to conclude that fish myosin alkali light chains originate from two different genes. This finding is in sharp contrast to all previous studies on vertebrate fast skeletal muscle myosins, which showed that in birds and mammals LC1 and LC3 are produced from a single gene by alternative RNA transcription and splicing, yielding proteins which differ only in their N-terminal segments. PMID- 1939602 TI - Sequence of an avian non-muscle caldesmon. AB - We have sequenced a cloned cDNA from a chicken gizzard library which encodes a short version of caldesmon with the properties expected for the non-muscle protein. The predicted protein is 524 amino acids long with a molecular mass of 60,174 daltons. Expression in bacteria produces a protein with an apparent molecular weight on SDS gels of 75-77,000, that comigrates with human platelet caldesmon. The expressed protein binds to F-actin and is retained on calmodulin Sepharose in the presence, but not absence of Ca2+. This non-muscle caldesmon isoform is identical to the smooth muscle protein at the N- and C-terminal ends, but is missing 232 amino acids from the centre. This central segment is thought to be helical, suggesting that non-muscle caldesmon is approximately 35 nm shorter, about 40 nm overall length, than smooth muscle caldesmon. PMID- 1939603 TI - Simulation of stochastic processes in motile crossbridge systems. AB - The underlying stochastic nature of many models of the actomyosin interaction should result in fluctuations in both force and shortening velocity. In classical experimental approaches involving intact or glycerinated muscle preparations these fluctuations are too small to resolve owing to the large numbers of crossbridges involved. However, new experimental techniques allow mechanical measurements to be made in systems in which small numbers of myosin heads act on a single actin filament, or small numbers of kinesin molecules act on a single tubulin filament. In these systems, stochastic effects should be evident. To understand better the nature of the expected stochastic effects, we have used computer simulation to investigate the fluctuations predicted by the original model for muscle crossbridge mechanics proposed by A.F. Huxley. We consider three situations: (1) the translation of actin or tubulin filaments by myosin or kinesin motors immobilized on a fixed substrate, (2) the production of tension by ensembles of immobilized myosin which involve the displacement of an elastic load, and (3) the fluctuations in axial displacement of a single, bipolar myosin thick filament interacting with actin filaments as in a sarcomere. In all three cases, fluctuations are clearly evident in simulations involving small numbers of motors. For case (1), we show that translation velocities can vary with crossbridge density. Whether one motor translates a filament faster, slower or at the same speed as many motors depends on the relative magnitudes of the attachment and detachment rate functions. Analytical expressions are provided to quantitate this relationship. For case (2), we show that fluctuations predicted assuming perfectly isometric conditions differ form those observed when the 'isometric state' is achieved against an elastic load. 'Elastic damping' of the fluctuations in the system results from the presence of many attached motors. In case (3) we show that in spite of the presence of stochastic fluctuations which can destabilize the uniformity of filament overlap in a sarcomere, the magnitude of thick filament displacement is less than might be anticipated over time periods of in vivo contraction. Taken together, these simulations allow one to better interpret experimental data in terms of current models of motor function. PMID- 1939604 TI - Distribution of actin filament lengths and their orientation measured by gel electrophoresis in capillaries. AB - F-actin was electrophoresed in capillary tubes filled with agarose gel. The use of capillary imparted high resistance on the gel allowing the use of high enough concentration of salts to keep F-actin polymerized, and allowed the application of high electric fields without liberating considerable amount of heat. The intensity profile of the electrophoretic band of F-actin showed a peak, which in 1% agarose in the electric field of 17.8 V cm-1 at 0 degree C, migrated at 3.4 cm hr-1. Microscopic observation of actin filaments extracted from different positions along the gel showed that during electrophoresis filaments distributed themselves in such a manner that the longest polymers migrated slowest and the shortest migrated fastest. Using this observation we calculated the weight and number distributions of filament lengths from corresponding experimental intensity profiles. Phalloidin-labelled F-actin oriented in the gel upon application of an electric field. F-actin showed unusual orientational response: it oriented rapidly when the field was applied, but relaxed very slowly when the field was removed. Orientation of F-actin varied within an electrophoretic band, longest polymers showing the best orientation and short oligomers and monomers not orienting at all. The degree of orientation increased with the size of the electric field. When F-actin was labelled with phalloidin before electrophoresis, it was no longer able to migrate in the gel, but the electric field oriented it in the same way as when it was labelled after the electrophoresis. These results show that the electrophoresis of F-actin in agarose fractionates it according to its length, that by using electrophoresis it is possible to rapidly obtain distribution of filament lengths, and that F-actin migrates in agarose by the process of reptation. PMID- 1939606 TI - Vertebrate muscle Z-line structure: an electron microscopic study of negatively stained myofibrils. AB - Structural features of the Z-lines of rabbit psoas muscle myofibrils have been studied in the electron microscope with a negative staining technique. The results obtained suggest the presence of about 20 nm periodicity in the structural organization of the Z-line region: a band pattern of five bands of extra density spaced about 20 nm apart was revealed in the Z-region and the Z filaments connecting actin filaments from neighbouring sarcomeres often appeared to be positioned at intervals of 17-20 nm. An electron microscopic investigation of the interaction in vitro of two major Z-line proteins, alpha-actinin and F actin, indicated that the positions of alpha-actinin bridges between actin filaments are defined by relative azimuthal positions of actin subunits. A possible arrangement of actin-linking macromolecular bridges in the Z-region is considered. It is supposed that the arrangement of the Z-filaments is related to the helical symmetry of actin-containing filaments. Also, the banded appearance of the Z-region is interpreted as arising from the arrangement of crossbridges connecting thin filaments of the same sarcomeres. PMID- 1939605 TI - Differential activation of myofibrils during fatigue in phasic skeletal muscle cells. AB - In fatigued muscles the T-system is swollen; thus the action potential may fail to travel along the T-system or the T-tubule terminal cisternae signal may fail to bring about TC Ca2+ release. This would lead to a decrease in the number of myofibrils activated and in force development, but if fatigue is the result of a generalized process, all the myofibrils would be affected equally leading to a lower activation of all of them. We have investigated this possibility in isolated twitch muscle fibres by giving them repetitive tetanic stimulations until fatigue developed. The behaviour of myofibrils was followed with cinemicrophotography. Before fatigue, no lack of shortening of myofibrils could be found. During fatigue groups of myofibrils became wavy. When exposed to caffeine, the wavy myofibrils disappeared and tension similar to the control developed. The tension-caffeine concentration relationship was shifted to the left after development of fatigue. In low Na+ solution fatigue developed faster and after reintroducing normal Ringer, tension recovered substantially. K contractures were smaller during fatigue. These results indicate that in this type of fatigue, a step in the EC coupling chain of events is involved in its development. PMID- 1939607 TI - Inter- and intra-specific variation in myosin light chain and troponin I composition in fast muscle fibres from two species of fish (genus Oreochromis) which have different temperature-dependent contractile properties. AB - The contractile properties and myofibrillar protein composition of fast muscle have been characterized in pure strains of two tropical fish Oreochromis niloticus and O. andersoni. Single fast muscle fibres were isolated from the abdominal myotomes and chemically skinned. The maximum tension-temperature relationships of fibres were similar at 25-30 degrees C, but diverged below 17 degrees C. At 10 degrees C, maximum tension was around 60% higher in O. andersoni (160 +/- 15 kN m-2) than O. niloticus (105 +/- 13 kN m-2) (mean +/- SD). The myofibrillar protein composition of fast fibres was investigated using one dimensional and two-dimensional gel electrophoresis and peptide mapping. The two Oreochromis species differed with respect to the composition of myosin light chains, troponin I and myosin heavy chains (V8 protease and chymotrypsin peptide maps). An unexpected finding was the presence of two isoforms of myosin light chain 1 in O. andersoni, with apparent molecular masses of 27.5 kDa (LC1f1) and 26.9 kDa (LC1f2). Individuals with LC1f1 (n = 20) and LC1f1 + LC1f2 (n = 12) were represented in the population studied. The myosin light chain 3 (LC3f) content of fibres was similar in both cases. Breeding experiments established that these intra-specific variations in isoform composition were heritable. Fast muscle from O. niloticus and O. andersoni contain two isoforms of troponin I (TNIfl + TNIf2) which were both expressed in single fibres. The identity of TNI was confirmed using a stationary phase troponin-C affinity column. Of the 20 O. niloticus studied seven contained only TNIf1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939608 TI - Identification and pattern of transitions of some developmental and adult isoforms of fast troponin T in some human and rat skeletal muscles. AB - Using a monoclonal antibody (F24) in an immunoblotting procedure, the composition of fast troponin T in several adult and developing skeletal muscles of rat and human was studied. With the exception of diaphragm, four isoforms of fast troponin T (HF1-HF4) were detected in all the adult human skeletal muscles investigated. Another isoform of fast troponin T undetectable in the adult human skeletal muscles, designated the fetal isoform (HFF1), was found to be present in all fetal skeletal muscles at 20 weeks of gestation except the diaphragm. Unlike isoform HF4 that was undetectable in all the fetal skeletal muscles, isoforms HF1 HF3 were present in all the human fetal skeletal muscles including the diaphragm. At least five isoforms of fast troponin T (AF1-AF5) could be detected in adult rat skeletal muscles. An additional isoform designated (D) appeared to be present in the rat diaphragm. In some muscles one of the isoforms, AF1, could be further resolved into two to three variants. The proportions and the level of expression of AF1-AF5 isoforms varied not only in different muscles but in some cases also in different parts of the same muscle. In addition to the adult isoforms, four other developmental isoforms termed fetal (FF1 and FF2) and neonatal (NF1 and NF2), were detected during the early development in the rat skeletal muscles. Their presence was first detected during the late fetal to early neonatal period and these isoforms were generally undetectable in a majority of the muscles after 1-2 months of age although their low level of expression persisted in a small number of muscles. PMID- 1939609 TI - Quantitative model for Schadler's isometric oscillations in insect flight and cardiac muscle. AB - Schadler and colleagues (1969, 1971) and Steiger (1977a) have found that tetanized insect fibrillar and cardiac muscles exhibit damped isometric oscillations in tension following a quick stretch. This behaviour cannot be explained by the conventional sliding filament model at full activation, or by including stretch activation in the obvious way. However, it is predicted by a sliding filament model which allows these muscles to be further activated by an increase in thin-filament tension even at high calcium levels (above 10(-5) M), providing the strength gamma of strain-activation coupling exceeds a critical value. Calculations from a comprehensive model of the actin-myosin contraction cycle suggest that this can be achieved if the phosphate release and head rotation steps are both regulated by calcium and thin-filament tension. The model also predicts a delayed tension rise following a quick release for subcritical values of gamma. Current knowledge of sarcomere structure and regulation of contractility in striated muscle indicates that this strain-activation mechanism alone cannot account for all stretch-activation phenomena, although many can be predicted if the regulatory filament is allowed to carry passive tension. PMID- 1939610 TI - Myosin heads contact with thin filaments in compressed relaxed skinned fibres of frog skeletal muscle. AB - When skinned skeletal muscle fibres with rest sarcomere length (L = 2.5 microns) are compressed by the addition of various concentrations ([PVP]) of polyvinylpyrrolidine, the relation between the 1,0 spacing (d) of thick filament lattice and [PVP] has been known to break at d of around 35 nm, resulting in a steeper slope of the relationship at d greater than 35 nm. To clarify the cause of this, X-ray diffraction and crosslinking experiments were carried out. The d versus [PVP] relationship of stretched fibres (L = 3.5 microns) breaks at a d of around 29 nm. The difference between these characteristic d values, 35-29 = 6 nm, is close to the diameter of thin filaments (8 nm). The crosslinking efficiency of formaldehyde between myosin heads and thin filament surface, measured by radial stiffness increase, was found to begin to markedly increase when the relaxed fibre with rest L was compressed to a d of nearly 35 nm. In addition to these results, the d versus [PVP] relationship obtained in rigor and in high [Mg2+] (30 mM) relaxing solutions, and the crosslinking efficiency seen in high [Mg2+] solutions supported our previous hypothesis that in normal relaxing solution (containing 1 mM Mg2+) the probability of myosin heads coming into contact with the thin filament surface abruptly increases at d near 35 nm in fibres with rest L. PMID- 1939612 TI - Maxillary protraction therapy: diagnosis and treatment. PMID- 1939611 TI - Parvalbumin in the cardiac muscle of normal and haemoglobin-myoglobin-free antarctic fish. AB - Three parvalbumin isotypes were isolated from the white muscle of haemoglobin myoglobin-free antarctic fish Channichthys rhinoceratus. Antibodies against the parvalbumin mixture were raised in rabbits and used for discovery, quantitation and isolation by affinity chromatography of parvalbumin in the cardiac muscle of three antarctic fish species: Channichthys rhinoceratus, Champsocephalus gunnari and Notothenia neglecta. The cardiac muscle of these species contains parvalbumin in concentration close to 1 mumol per kg wet weight. PMID- 1939613 TI - Reasons for broken and canceled appointments in a British orthodontic clinic. PMID- 1939614 TI - In-vivo remineralization after air-rotor stripping. PMID- 1939615 TI - Determining physiologic archforms. PMID- 1939616 TI - Ectopic maxillary second molars. PMID- 1939617 TI - A sliding bridge appliance for space closure. PMID- 1939619 TI - Derotating a tooth with a lingual rotation tie. PMID- 1939618 TI - 1990 JCO study of orthodontic diagnosis and treatment procedures. 1. Results and trends. PMID- 1939620 TI - Convertible Haas-type rapid palatal expander. PMID- 1939621 TI - A cephalometric analysis based on natural head position. PMID- 1939622 TI - 1990 JCO study of orthodontic diagnosis and treatment procedures. 2. Breakdowns of selected variables. PMID- 1939623 TI - Computer-aided space analysis. PMID- 1939624 TI - Modified maxillary splint for Class II, division 1 treatment. PMID- 1939626 TI - Finishing and detailing with a preadjusted appliance system. PMID- 1939625 TI - A plier for tying continuous ligatures. PMID- 1939627 TI - 1990 JCO study of orthodontic diagnosis and treatment procedures. 3. More breakdowns of selected variables. PMID- 1939628 TI - Panoramic surveys and the missing mesiodens. PMID- 1939629 TI - The effect of a contingency contracting procedure on patient compliance with removable retention. PMID- 1939630 TI - A nickel titanium separating spring. PMID- 1939631 TI - Banded mandibular adjustable retainer. PMID- 1939632 TI - Quality in orthodontic practice. PMID- 1939633 TI - Strength of ceramic brackets in shear and torsion tests. PMID- 1939634 TI - Clinical considerations in the use of retraction mechanics. PMID- 1939635 TI - Clinical applications of superelastic nickel titanium wires. PMID- 1939636 TI - Orthodontic office design. Planning a sterilization area. PMID- 1939637 TI - Molecular genetics of intestinal glucose transport. PMID- 1939638 TI - Genetic causes of aortic aneurysms. Unlearning at least part of what the textbooks say. PMID- 1939639 TI - Antimalarial effects of peptide inhibitors of a Plasmodium falciparum cysteine proteinase. AB - We previously identified a Plasmodium falciparum trophozoite cysteine proteinase (TCP) and hypothesized that it is required for the degradation of host hemoglobin by intraerythrocytic malaria parasites. To test this hypothesis and to evaluate TCP as a chemotherapeutic target, we examined the antimalarial effects of a panel of peptide fluoromethyl ketone proteinase inhibitors. For each inhibitor, effectiveness at inhibiting the activity of TCP correlated with effectiveness at both blocking hemoglobin degradation and killing cultured parasites. Benzyloxycarbonyl (Z)-Phe-Arg-CH2F, the most potent inhibitor, inhibited TCP at picomolar concentrations and blocked hemoglobin degradation and killed parasites at nanomolar concentrations. Micromolar concentrations of the inhibitor were nontoxic to cultured mammalian cells. These results support the hypothesis that TCP is a necessary hemoglobinase and suggest that it is a promising chemotherapeutic target. PMID- 1939640 TI - Activation of T lymphocytes in dengue virus infections. High levels of soluble interleukin 2 receptor, soluble CD4, soluble CD8, interleukin 2, and interferon gamma in sera of children with dengue. AB - It has been reported that the severe complication of dengue virus infection, dengue hemorrhagic fever (DHF) is much more commonly observed during secondary dengue virus infections than primary infections. In order to elucidate the role of T lymphocytes in the pathogenesis of DHF, we attempted to determine whether T lymphocytes are activated in vivo during dengue virus infections, by examining the levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4), soluble CD8 (sCD8), interleukin-2 (IL-2) and interferon-gamma (IFN gamma) in the sera of 59 patients with DHF and 41 patients with dengue fever (DF). The levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma were significantly higher in the acute sera of patients with DHF than in the sera of healthy children (P less than 0.001 for all markers). The acute sera of patients with DF contained higher levels of sIL-2R, sCD4, IL-2, and IFN gamma than the sera of healthy children (P less than 0.001 for sIL-2R, IL-2, and IFN gamma; P less than 0.05 for sCD4), but did not have elevated levels of sCD8. The levels of sIL-2R (P less than 0.05), sCD4 (P less than 0.001), and sCD8 (P less than 0.001) were higher in DHF than in DF on days 3 4 after the onset of fever. The levels of IL-2 and IFN gamma in patients with DHF were highest 1 d before defervescence. There were no significant differences in the levels of sIL-2R, sCD4, sCD8, IL-2, and IFN gamma among grades 1, 2, and 3 of DHF. These results indicate (a) T lymphocytes are activated and produce IL-2 and IFN gamma in vivo during DHF and DF, (b) CD4+ T lymphocytes are activated in DHF and DF, and the level of activation is higher in DHF than in DF, and (c) activation of CD8+ T lymphocytes is evident in DHF, but not in DF. PMID- 1939641 TI - Influence of apolipoprotein E polymorphism on apolipoprotein B-100 metabolism in normolipemic subjects. AB - This study examined apolipoprotein (apo) B metabolism in normolipemic subjects homozygous for the apo E2 (n = 4), apo E3 (n = 5), or apo E4 (n = 5) phenotype. Radioiodinated very low density lipoprotein (VLDL1) (ultracentrifuge flotation rate [Sf] 60-400) and VLDL2 (Sf 20-60) were injected into volunteers and the conversion of apo B was followed through intermediate density lipoprotein (IDL) to low density lipoprotein (LDL). Subjects homozygous for E3 converted approximately 50% of LVDL2 to LDL, the remainder being lost by direct catabolism. Those with the E2 phenotype produced less VLDL1, but converted more of it to VLDL2 (compared to E3 subjects). They displayed a characteristic dyslipidemia with the presence of slowly catabolized VLDL1 and VLDL2 remnants. LDL levels were low owing to increased direct catabolism of VLDL2 and IDL and a reduced efficiency of delipidation; only 25% of VLDL2 apo B was directed to LDL production. In contrast, E4 subjects converted more VLDL2 apo B to LDL than E3 subjects. About 70% of VLDL2 apo B was found in LDL; direct catabolism of VLDL and IDL was reduced as was the fractional catabolic rate of LDL (0.2 vs. 0.26 in E3 subjects). These changes in the VLDL----IDL----LDL metabolic cascade can in part be explained by alterations in hepatic LDL receptors with E2 subjects having higher and E4 subjects lower activities than those in E3 homozygotes. PMID- 1939642 TI - Mesangial cell autoantigens in immunoglobulin A nephropathy and Henoch-Schonlein purpura. AB - The autoantigen(s) that we have previously described in human glomeruli, recognized in IgA nephropathy, has (have) been identified as mesangial cell in origin. Cultured mesangial cells expressed 48- and 55-kD components binding IgG isotype autoantibodies (IgG-MESCA) present in sera of patients with both IgA nephropathy and Henoch-Schonlein purpura (HSP). IgG-MESCA were not detected in sera of normals, or patients with other autoimmune-mediated glomerulonephritides: anti-glomerular basement membrane disease, Wegener's granulomatosis, or in IgM mesangial proliferative disease. Binding specificity was proven by F(ab')2 studies in enzyme-linked immunosorbent assay (ELISA) and Western blotting, and there was no significant affinity of IgA or IgM immunoglobulins. Fluorescein isothiocyanate-conjugated IgG from ELISA-positive sera localized to the mesangium and peripheral capillary loops of glomeruli, supporting the belief that the antigen is expressed in normal human renal tissue. However, only about one third of mesangial cells in culture showed affinity for IgG from ELISA-positive sera, suggesting variable expression of the antigen(s) in vitro. The only autoantigen(s) present in glomeruli, and extractable from whole normal glomeruli by the techniques employed, localized on the mesangial cell. In both IgA nephropathy and HSP, autoimmunity was intermittently present, with fluctuating levels of IgG-MESCA detectable in sera. There were positive correlations with the degree of glomerular injury assessed by erythrocyturia and proteinuria in IgA nephropathy, but significance was reached with only the degree of hematuria in HSP. These findings suggest a contributing role in the pathogenesis of the mesangial proliferative lesions and demonstrate autoimmunity common to both IgA nephropathy and HSP. PMID- 1939643 TI - Effect of denervation on the expression of two glucose transporter isoforms in rat hindlimb muscle. AB - Denervation rapidly (within 24 h) induces insulin resistance of several insulin responsive pathways in skeletal muscle, including glucose transport; resistance is usually maximal by 3 d. We examined the effect of denervation on the expression of two glucose transporter isoforms (GLUT-1 and GLUT-4) in rat hindlimb muscle; GLUT-4 is the predominant species in muscle. 1 d postdenervation, GLUT-1 and GLUT-4 mRNA and protein concentrations were unchanged. 3 and 7 d postdenervation, GLUT-4 mRNA and protein (per microgram DNA) were decreased by 50%. The minor isoform, GLUT-1 mRNA increased by approximately 500 and approximately 100%, respectively, on days 3 and 7 while GLUT-1 protein increased by approximately 60 and approximately 100%. The data suggest that the insulin resistance of glucose transport early after denervation does not reflect a decrease in total glucose transporter number; however, decreased GLUT-4 expression may contribute to its increased severity after 3 d. Parallel decreases in GLUT-4 mRNA and GLUT-4 protein postdenervation are consistent with pretranslational regulation; GLUT-1 expression may be regulated pre- and posttranslationally. The cell type(s) which overexpress GLUT-1 postdenervation need to be identified. Nervous stimuli and/or contractile activity may modulate the expression of GLUT-1 and GLUT-4 in skeletal muscle tissue. PMID- 1939644 TI - Evidence from oocyte expression that the erythrocyte water channel is distinct from band 3 and the glucose transporter. AB - It has been proposed that the mercurial-sensitive water transporter in mammalian erythrocytes is the anion exchanger band 3 (AE1) and/or the glucose transporter, band 4.5 (GLUT1). Using a functional assay for water channel expression in Xenopus oocytes (Zhang, R., K. A. Logee, and A. S. Verkman. 1990. J. Biol. Chem. 265:15375-15378), we compared osmotic water permeability (Pf) of oocytes injected with water, reticulocyte mRNA, AE1 mRNA, and GLUT1 mRNA. Injection of oocytes with 5-50 ng of in vitro-transcribed AE1 mRNA had no effect on Pf, but increased trans-stimulated 36Cl uptake greater than fourfold in a dinitro-disulfonic stilbene (DNDS)-inhibitable manner. Injection with 1-50 ng of in vitro transcribed GLUT1 mRNA increased 3H-methylglucose uptake greater than 15-fold in a cytochalasin B-sensitive manner and increased Pf from (3.7 +/- 0.4) x 10(-4) cm/s (SE, n = 16, 10 degrees C) in water-injected oocytes up to (13 +/- 1) x 10( 4) cm/s (n = 18). Both the increments in sugar and water transport were inhibited by cytochalasin B (25 microM) and phloretin (0.2 mM); neither was inhibited by 0.3 mM HgCl2. In oocytes injected with 50 ng of rabbit reticulocyte mRNA, the Pf of (18 +/- 2) x 10(-4) cm/s (n = 18) was reduced to (4.0 +/- 0.6) x 10(-4) cm/s (n = 10) by HgCl2, but was not inhibited by DNDS (0.4 mM), cytochalasin B or phloretin. Coinjection of reticulocyte mRNA with antisense oligodeoxyribonucleotides against AE1 or GLUT1 did not affect Pf, but inhibited completely the incremental uptake of 36Cl or 3H-methylglucose, respectively. Expression of size-fractionated mRNA from reticulocyte gave a 2-2.5-kb size for water channel mRNA, less than the 4-4.5-kb size for the Cl transporter. These results provide evidence that facilitated water transport in erythrocytes is mediated not by bands 3 or 4.5, but by distinct water transport protein(s). PMID- 1939645 TI - von Willebrand factor binding to platelet GpIb initiates signals for platelet activation. AB - The hypothesis that von Willebrand factor (vWF) binding to platelet membrane glycoprotein Ib (GpIb) initiates intracellular pathways of platelet activation was studied. We measured the biochemical responses of intact human platelets treated with ristocetin plus vWF multimers purified from human cryoprecipitate. vWF plus ristocetin causes the breakdown of phosphatidylinositol 4,5 bisphosphate, the production of phosphatidic acid (PA), the activation of protein kinase C (PKC), increase of ionized cytoplasmic calcium ([Ca2+]i), and the synthesis of thromboxane A2. PA production, PKC activation, and the rise of [Ca2+]i stimulated by the ristocetin-induced binding of vWF multimers to platelets are inhibited by an anti-GpIb monoclonal antibody, but are unaffected by anti-GpIIb-IIIa monoclonal antibodies. Indomethacin also inhibits these responses without impairing platelet aggregation induced by vWF plus ristocetin. These results indicate that vWF binding to platelets initiates specific intraplatelet signaling pathways. The mechanism by which this occurs involves an arachidonic acid metabolite-dependent activation of phospholipase C after vWF binding to platelet membrane GpIb. This signal then causes PKC activation and increases of [Ca2+]i, which promote platelet secretion and potentiate aggregation. PMID- 1939646 TI - Regulation of transforming growth factor-beta 1 gene expression by glucocorticoids in normal human T lymphocytes. AB - Glucocorticoids (GC) modulate immune function in a number of ways, including suppression of T cell proliferation and other IL-2-mediated T cell functions. These inhibitory effects are similar to those induced by transforming growth factor-beta 1 (TGF-beta 1), a cytokine with potent T cell inhibiting activities. We examined the hypothesis that GC effects may be at least partially achieved through modulation of the expression of the TGF-beta 1 gene in activated T cells. Normal T cells were cultured with or without purified phytohemagglutinin (PHA-p) and 4 beta-phorbol 12-myristate 13-acetate (PMA) in the presence or absence of the synthetic GC, dexamethasone (100-200 micrograms/ml). The production of latent and active forms of TGF beta by these cells were analyzed by immunoblotting and bioassays. The steady-state levels of TGF-beta 1 mRNA were analyzed in total RNA from these cells by Northern hybridizations using a human TGF-beta 1 cDNA. The results showed that dexamethasone caused an increase in TGF beta production and a dose-dependent two to fourfold increase in TGF-beta 1 mRNA in activated as well as in unstimulated T cells, 1 h after exposure of the cultures to the steroid. The increase in TGF-beta 1 mRNA levels by dexamethasone was further potentiated two to threefold by cycloheximide, suggesting that the steroid effect may be due to inhibition of the synthesis of proteins that decrease TGF-beta 1 gene transcription or the stability of its transcripts. Finally, in vitro nuclear transcription studies indicated the dexamethasone effects on TGF-beta 1 gene expression to be largely transcriptional. PMID- 1939647 TI - Systemic lysis protects against the effects of platelet activation during coronary thrombolysis. AB - Systemic lysis may protect against the platelet activation and ongoing thrombosis associated with coronary thrombolysis. To address this hypothesis, we compared urokinase and tissue-type plasminogen activator (t-PA) given intravenously in a chronic, canine model of coronary thrombosis. T-PA 10 micrograms/kg per min induced reperfusion in 55 +/- 7 min but complete reocclusion occurred in 9/10 animals. Reocclusion was prevented by combining t-PA with 7E3, an antibody to the platelet glycoprotein IIb/IIIa which abolished ex vivo platelet aggregation. A similar time to reperfusion was seen with urokinase 750-1,000 U/kg per min. In contrast to t-PA, complete reocclusion occurred in only 1/20 cases (P less than 0.001 vs. t-PA), despite evidence of continued platelet activation in vivo and platelet aggregation ex vivo. Furthermore, this did not reflect a difference in the clearance of the two plasminogen activators. However, plasma fibrinogen was undetectable after urokinase in contrast with t-PA. Furthermore, in animals treated with prourokinase 20 micrograms/kg per min, reocclusion (4/7) correlated with the degree of systemic lysis. To determine whether platelet activation modified the response to urokinase, it was combined with 7E3. 7E3 0.8 mg/kg reduced the time to reperfusion with t-PA (30 +/- 5, n = 6; P = 0.025), but not with urokinase (56 +/- 8 vs. 62 +/- 6, P = ns). Systemic lysis protects against the propensity of continued thrombosis during coronary thrombolysis to delay reperfusion and induce reocclusion. This may modify the requirement for adjunctive antiplatelet therapy. PMID- 1939648 TI - Cytogenetic and molecular genetic studies of follicular and papillary thyroid cancers. AB - Cytogenetic studies have shown frequent clonal abnormalities in papillary carcinoma (PTC) and follicular carcinoma (FTC). Loss of heterozygosity (LOH) may suggest the presence of tumor suppressor genes and has not been reported in these neoplasms. These studies were undertaken to determine if consistent chromosomal abnormalities are associated with thyroid cancer, to determine likely regions for molecular genetic investigations, and to determine if there is allelic loss in thyroid tumors. Cytogenetic analysis of 26 PTC and 5 FTC showed clonal abnormalities in 9 and included -Y, +5, or inv(10)(q11.2q21.2) in PTC, and -Y or near haploidy in FTC. Using DNA probes specific for chromosomes 1, 3, 10, 16, and 17, we carried out restriction fragment length polymorphism analysis on 6 FTC, 3 follicular adenomas (FA), and 12 PTC. LOH of all informative loci on chromosome 3p was observed in all 6 FTC, but not in FA or PTC. No LOH was observed for loci mapped to chromosome 10 in PTC. Our results suggest: cytogenetic abnormalities of chromosome 10q are associated with PTC; cytogenetic and molecular abnormalities of chromosome 3 are associated with FTC; and a tumor suppressor gene may be present on the short arm of chromosome 3 important for the development or progression of FTC. PMID- 1939649 TI - Accumulation of hyaluronan and tissue edema in experimental myocardial infarction. AB - Experimental myocardial infarction was induced in rats. The myocardial accumulation of hyaluronan (HA) and water during the development of infarction was measured. The extractable HA content of the infarcted area increased progressively from day 1 and on day 3 reached a threefold increase compared with the HA amounts in myocardium of sham operated controls. The relative water content of infarcted areas also increased progressively reaching a maximum value by day 3 and was strongly correlated with the HA accumulation. Affinity histochemistry visualized a thin rim of HA in the endoperimysium in healthy myocardium. By day 2 an interstitial edema with inflammatory cells was apparent. The widened endoperimysium stained extensively for HA. By its water-binding ability, interstitial accumulation of HA will contribute to the interstitial edema in infarcted myocardial tissue. An interstitial edema is likely to influence the electromechanical characteristics of the myocardium and facilitate reentry phenomena due to a loss of contact between muscle cells. The edema also induces an increased extracellular pressure and an altered myocardial wall compliance that might impair myocardial microcirculation. The findings are relevant to an understanding of the beneficial effect of hyaluronidase treatment in limiting cellular damage during myocardial ischemia. PMID- 1939650 TI - Sjogren-Larsson syndrome. Deficient activity of the fatty aldehyde dehydrogenase component of fatty alcohol:NAD+ oxidoreductase in cultured fibroblasts. AB - Sjogren-Larsson syndrome (SLS) is an inherited disorder associated with impaired fatty alcohol oxidation due to deficient activity of fatty alcohol:NAD+ oxidoreductase (FAO). FAO is a complex enzyme which consists of two separate proteins that sequentially catalyze the oxidation of fatty alcohol to fatty aldehyde and fatty acid. To determine which enzymatic component of FAO was deficient in SLS, we assayed fatty aldehyde dehydrogenase (FALDH) and fatty alcohol dehydrogenase in cultured fibroblasts from seven unrelated SLS patients. All SLS cells were selectively deficient in the FALDH component of FAO, and had normal activity of fatty alcohol dehydrogenase. The extent of FALDH deficiency in SLS cells depended on the aliphatic aldehyde used as substrate, ranging from 62% of mean normal activity using propionaldehyde as substrate to 8% of mean normal activity with octadecanal. FALDH activity in obligate SLS heterozygotes was partially decreased to 49 +/- 7% of mean normal activity using octadecanal as substrate. Differential centrifugation studies in fibroblasts indicated that this FALDH enzyme was largely particulate; soluble FALDH activity was normal in SLS cells. Intact SLS fibroblasts oxidized octadecanol to fatty acid at less than 10% of the normal rate, but oxidized free octadecanal normally, suggesting that the FALDH affected in SLS is chiefly involved in the oxidation of fatty alcohol to fatty acid. These results show that the primary enzymatic defect in SLS is the FALDH component of the FAO complex, which leads to deficient oxidation of fatty aldehyde derived from fatty alcohol. PMID- 1939651 TI - Evidence for direct estrogen regulation of the human gonadotropin-releasing hormone gene. AB - This study is an attempt to determine whether estrogen could directly regulate human gonadotropin-releasing hormone (GnRH) gene expression. Human GnRH expression vectors were constructed by fusing various 5' flanking regions of the human GnRH gene upstream of the luciferase reporter gene (LUC) or the thymidine kinase promoter linked to the chloramphenicol acetyltransferase reporter gene (CAT). These constructs were transiently transfected into a human choriocarcinoma cell line (JEG-3) and LUC or CAT activity was measured after either no treatment or treatment with various concentrations of estradiol. A stimulatory estrogen response element (ERE) was localized to a 32-bp region between -547 and -516 bp. To determine whether estrogen receptor bound to this region of the gene, we performed DNase I footprinting using purified calf uterine estrogen receptor. DNase I footprinting demonstrates a strong footprint between -567 and -514 bp of the human GnRH gene. In addition, an avidin-biotin complex DNA-binding assay demonstrated that a biotinylated DNA fragment containing -541 to -517 bp of the human GnRH gene bound 35S-labeled estrogen receptor as well as a biotinylated DNA fragment containing the xenopus vitellogenin ERE. On the other hand, the negative control biotinylated DNA fragment derived from adenovirus 5 bound insignificant amounts of 35S-labeled estrogen receptor. Both the GnRH ERE and vitellogenin ERE bound 35S-labeled estrogen receptor with high affinity (approximately 1 nM). These data indicate that the human GnRH gene contains an ERE sufficient to mediate a stimulatory response to estrogen in heterologous cells. Based upon these data we hypothesize that the human GnRH gene might also be directly regulated by estrogen in the hypothalamus, and that this regulation may explain the GnRH hypersecretion observed at the time of the preovulatory luteinizing hormone (LH) surge. PMID- 1939652 TI - Evidence for persistent hepatitis C virus (HCV) infection in hemophiliacs. AB - Hepatitis C virus (HCV) is the major etiologic agent associated with non-A, non-B hepatitis. This study was designed to assess virologic and serologic markers in hemophiliacs exposed to non-heat-treated and/or virus-inactivated plasma derivatives. Serial bleeds from 48 hemophilic patients were analyzed for the presence of HCV viral RNA sequences as detected by polymerase chain reaction (PCR) and antibodies to structural (core) and nonstructural (C-100 and 33C) proteins by specific dot immunoblot assay. All patients exposed to non-heat treated products, and four of six patients exposed only to virus inactivated products, had evidence of HCV infection. However, over the 5-yr study period, six exposed patients (13%) consistently lacked detectable anti-C-100 and seven (15%) lost this antibody. HCV viremia (PCR positive) was found in 91% of exposed patients, and was significantly more frequent in HIV seropositive hemophiliacs (P less than 0.05). Six patients had high antibody level to HCV and elevated ALT, but appeared to clear viremia. Four hemophiliacs were HCV seropositive but lacked detectable viremia. These data indicate that hemophiliacs remain persistently infected by HCV and that antibody to the core antigen of HCV is a reliable marker of this transfusion transmissible agent. PMID- 1939653 TI - Factor XSanto Domingo. Evidence that the severe clinical phenotype arises from a mutation blocking secretion. AB - Factor X (FX) is a vitamin K-dependent plasma protein required for the intrinsic and extrinsic pathways of blood coagulation. FXSanto Domingo is a hereditary FX deficiency which is characterized clinically by a severe bleeding diathesis. The proposita has a FX activity of less than 1% and a FX antigen of less than 5%. We have determined the molecular basis of the defect in the FXSanto Domingo gene by amplification of all eight exons with polymerase chain reaction and subsequent sequence analysis. The patient is homozygous for a G----A transition in exon I at codon -20 (numbering the alanine at the NH2 terminus of the mature protein as +1), resulting in the substitution of arginine for glycine in the carboxy terminal part of the signal peptide. This amino acid change occurs near the presumed cleavage site of the signal peptidase. We hypothesized that the mutation might prevent cleavage by the signal peptidase which in turn would impair proper secretion of the FX protein. To test this hypothesis, we compared the expression of wild type and mutant FX cDNA in a human kidney cell line. Wild type and mutant constructs in the expression vector pCMV4 were introduced into the human embryonic kidney cell line 293 by calcium phosphate transfection. FX antigen levels in the supernatant of the cells harboring the wild type construct were 2.4 micrograms/10(7) cells per 24 h, whereas antigen levels in media from cells containing the FXSanto Domingo construct were undetectable. No FX antigen was detected in the cell lysates of cells transfected with the mutant construct. To insure that the difference in protein levels was not due to a difference in steady state levels of mRNA, Northern analysis was performed on RNA from the cell lysates of both constructs. The results showed a transcript of the same size, present in roughly equal amounts, in both cases. Thus, the defect in the signal sequence of FXSanto Domingo exerts its effect posttranscriptionally. FXSanto Domingo is the first described example of a bleeding diathesis due to a mutation in the signal sequence. PMID- 1939654 TI - Inhibition of platelet function by an aspirin-insensitive endothelial cell ADPase. Thromboregulation by endothelial cells. AB - We previously reported that platelets become unresponsive to agonists when stimulated in combined suspension with aspirin-treated human umbilical vein endothelial cells. Inhibition occurred concomitant with metabolism of platelet derived endoperoxides to prostacyclin by endothelial cells. We now demonstrate that if aspirin-treated platelets which fully respond to appropriate doses of agonists are exposed to aspirin-treated endothelial cells, they remain unresponsive despite absence of prostacyclin. Platelet inhibition is due in large part to ecto-ADPase activity on the endothelial cells. This was established by incubating aspirin-treated endothelial cells with 14C-ADP. Radio-thin layer chromatography and aggregometry demonstrated that 14C-ADP and induction of platelet activation decreased rapidly and concurrently. AMP accumulated transiently, was further metabolized to adenosine, and deaminated to inosine. The apparent Km of the endothelial cell ADPase was 33-42 microM and the Vmax 17-43 nmol/min per 10(6) cells, values in the range of antithrombotic potential. Thus, at least three complementary systems in human endothelial cells control platelet responsiveness: a cell-associated, aspirin-insensitive ADPase which functions in parallel with fluid phase autacoids such as the aspirin-inhibitable eicosanoids, and the aspirin-insensitive endothelium-derived relaxing factor. PMID- 1939655 TI - In vitro growth rate of placental fibroblasts is developmentally regulated. AB - Placental cells of mesenchymal origin were used to study the regulation of fetal growth at the cellular level. A significant difference in the in vitro growth rates of placental fibroblasts was observed as a function of gestational age. Cells derived from 10-19-wk placentae exhibited proliferative rates two to three times greater than cells derived from 7-9-wk placentae (16-30 h vs. 30-60 h, P less than 0.001). The proliferation rate remained stable throughout multiple passages in culture. Additionally, these two groups of cell strains exhibited marked differences in their responsiveness to mitogenic stimuli. Using maximal effective concentrations, insulin-like growth factor I interacted synergistically with epidermal growth factor and fibroblast growth factor to stimulate DNA synthesis in cells derived from 10-19-wk placentae. By contrast, the interaction of insulin-like growth factor 1 with epidermal growth factor and fibroblast growth factor exhibited significantly less synergy in 7-9-wk cells. These findings argue that the accelerated growth rate of human fetal cells results primarily from developmental events intrinsic to the cells and is associated with enhanced responsiveness to the mitogenic action of peptide growth factors. PMID- 1939656 TI - Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. AB - Urethral obstruction produces increased voiding frequency (0.7 +/- 0.06 to 1.1 +/ 0.08 h-1) and hypertrophy of the urinary bladder (89 +/- 1.7 to 708 +/- 40 mg) with profound increments in the dimensions of afferent (4, 6) and efferent neurons (299 +/- 4.7 to 573 +/- 8.6 microns2) supplying this organ in the rat. We discovered that hypertrophied bladders of rat and human contain significantly more nerve growth factor (NGF) per milligram wet weight, protein, and DNA than normal bladders. The temporal correlation between NGF content, neuronal hypertrophy, and bladder weight was consistent with a role for this growth factor in the neurotrophic effects associated with obstruction. Autoimmunity to NGF abolished the hypertrophy of NGF-sensitive bladder neurons in the pelvic ganglion after obstruction. Relief of urethral obstruction reduced bladder size (349 +/- 78 mg), but neuronal hypertrophy (460.2 +/- 10.2 microns2) and elevated NGF levels were only partially reversed. Bladder hypertrophy (133 +/- 4.3 mg) induced by osmotic diuresis slightly increased ganglion cell area (365.2 +/- 6.1 microns2) and only doubled NGF content of the bladder. These findings provide important new evidence that parenchymal cells in the hypertrophied bladder can synthesize NGF and possibly other molecular messengers that act to alter the size and function of neurons in adult animals and man. PMID- 1939657 TI - Molecular and metabolic basis for the metabolic disorder normotriglyceridemic abetalipoproteinemia. AB - We have previously described a disorder, normotriglyceridemic abetalipoproteinemia, that is characterized by the virtual absence of plasma low density lipoproteins and complete absence of apoB-100, but with apparently normal secretion of triglyceride-rich lipoproteins containing apoB-48. The patient's plasma lipoproteins were shown on polyacrylamide gels and by antibody mapping to have a new truncated apoB variant, apoB-50, circulating along with her apoB-48. We have found this individual to be homozygous for a single C-to-T nucleotide substitution at apoB codon 2252, which produces a premature in-frame stop codon. Thus, this is a rare example of homozygous hypobetalipoproteinemia. Electron photomicrographs revealed that the diameters of particles in the d less than 1.006 g/ml lipoprotein fraction, in both the postprandial and postabsorptive state, are bimodally distributed. The molar ratio of apoE to apoB in these particles is 3.5:1, similar to normal VLDL. The plasma LDL interval contains both spherical and cuboidal particles. Autologous reinfusion of labeled d less than 1.006 g/ml lipoproteins showed exponential disappearance from plasma, with an apparent half-removal time of 50 min, somewhat slower than for normal chylomicrons but within the normal range for VLDL. The calculated production rate for apoB was within the normal range in this subject. A very small amount of label was found briefly in the IDL fraction, but none at any time in LDL or HDL. Therefore, because LDL particles that contain apoB-50 lack the putative ligand domain of the LDL receptor, we conclude that the very low level of LDL is due to the rapid removal of the abnormal VLDL particles before their conversion to LDL can take place. PMID- 1939658 TI - Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease. AB - A viable autosomal recessive mutation (named fch, or ferrochelatase deficiency) causing jaundice and anemia in mice arose in a mutagenesis experiment using ethylnitrosourea. Homozygotes (fch/fch) display a hemolytic anemia, photosensitivity, cholestasis, and severe hepatic dysfunction. Protoporphyrin is found at high concentration in erythrocytes, serum, and liver. Ferrochelatase activity in various tissues is 2.7-6.3% of normal. Heterozygotes (+/fch) are not anemic and have normal liver function; they are not sensitive to light exposure; ferrochelatase activity is 45-65% of normal. Southern blot analysis using a ferrochelatase cDNA probe reveals no gross deletion of the ferrochelatase gene. This is the first spontaneous form of erythropoietic protoporphyria in the house mouse. Despite the presence in the mouse of clinical and biochemical features infrequent in the human, this mutation may represent a model for the human disease, especially in its severe form. PMID- 1939660 TI - Active site-blocked factor IXa prevents intravascular thrombus formation in the coronary vasculature without inhibiting extravascular coagulation in a canine thrombosis model. AB - To assess the contribution of Factor IX/IXa, to intravascular thrombosis, a canine coronary thrombosis model was studied. Thrombus formation was initiated by applying current to a needle in the circumflex coronary artery. When 50% occlusion of the vessel developed, the current was stopped and animals received an intravenous bolus of either saline, bovine glutamyl-glycyl-arginyl-Factor IXa (IXai), a competitive inhibitor of Factor IXa assembly into the intrinsic Factor X activation complex, bovine Factor IX, or heparin. Animals receiving saline or Factor IX developed coronary occlusion due to a fibrin/platelet thrombus in 70 +/ 11 min. In contrast, infusion of IXai prevented thrombus formation completely (greater than 180 min) at doses of 460 and 300 micrograms/kg, and partially blocked thrombus formation at 150 micrograms/kg. IXai attenuated the accumulation of 125I-fibrinogen/fibrin at the site of the thrombus by approximately 67% (P less than 0.001) and resulted in approximately 26% decrease in serotonin release from platelets in coronary sinus (P less than 0.05). Hemostatic variables in animals receiving IXai, remained within normal limits. Animals given heparin in a concentration sufficient to prevent occlusive thrombosis had markedly increased bleeding, whereas heparin levels that maintained extravascular hemostasis did not prevent intracoronary thrombosis. This suggests that Factor IX/IXa can contribute to thrombus formation, and that inhibition of IXa participation in the clotting mechanism blocks intravascular thrombosis without impairing extravascular hemostasis. PMID- 1939659 TI - Dysregulation of in vitro cytokine production by monocytes during sepsis. AB - The production by monocytes of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF alpha) in intensive care unit (ICU) patients with sepsis syndrome (n = 23) or noninfectious shock (n = 6) is reported. Plasma cytokines, cell-associated cytokines within freshly isolated monocytes and LPS-induced in vitro cytokine production were assessed at admission and at regular intervals during ICU stay. TNF alpha and IL-6 were the most frequently detected circulating cytokines. Despite the fact that IL-1 alpha is the main cytokine found within monocytes upon in vitro activation of cells from healthy individuals, it was very rarely detected within freshly isolated monocytes from septic patients, and levels of cell-associated IL-1 beta were lower than those of TNF alpha. Cell-associated IL 1 beta and TNF alpha were not correlated with corresponding levels in plasma. Upon LPS stimulation, we observed a profound decrease of in vitro IL-1 alpha production by monocytes in all patients, and of IL-1 beta, IL-6, and TNF alpha in septic patients. This reduced LPS-induced production of cytokines was most pronounced in patients with gram-negative infections. Finally, monocytes from survival patients, but not from nonsurvival ones recovered their capacity to produce normal amounts of cytokines upon LPS stimulation. In conclusion, our data indicate an in vivo activation of circulating monocytes during sepsis as well as in noninfectious shock and suggest that complex regulatory mechanisms can downregulate the production of cytokines by monocytes during severe infections. PMID- 1939662 TI - Comparison of sandwich-ELISA and GM1-ELISA for the detection of Escherichia coli thermolabile enterotoxin. AB - Two different microtiter plate ELISA tests were devised for the detection of Escherichia coli thermolabile toxin (LTh) either free or extracted from isolated colonies. Both tests used as detection systems purified anti-LTh rabbit immunoglobulins conjugated to biotin, streptavidin peroxidase and TMB. The tests differed by their capture phase which was the GM1-ganglioside for GM1-ELISA and purified anti-LTh rabbit immunoglobulins for sandwich ELISA. The two methods were rapid since they could be performed in less than 2 hours. The detection limits for purified LT were 50 pg/ml and 1.3 ng/ml for sandwich ELISA and GM1-ELISA respectively. For the detection of toxinogenic isolates the extraction buffer containing Triton X-100 was always superior to polymyxin buffer. Using the polymyxin extraction buffer the sandwich ELISA was again more sensitive than the GM1-ELISA since a lower number of isolated colonies could be used for the detection of positive strains. With the Triton X-100 buffer both ELISAs could detect positive strains using a single colony but the sandwich ELISA gave the highest delta OD. We concluded that our sandwich ELISA can rapidly detect either the free Escherichia coli thermolabile toxin or LTh producing strains and could be applied routinely. PMID- 1939661 TI - Lactate activates ATP-sensitive potassium channels in guinea pig ventricular myocytes. AB - The functional significance of cardiac ATP-sensitive potassium channels remains controversial because of the discrepancy between the low levels of ATP at which activation of the channels occurs and the much higher levels of ATP maintained during myocardial ischemia. We studied the effects of (+)-lactate, which accumulates in large quantity as a result of increased glycolysis during ischemia, on ATP-sensitive potassium channels in adult guinea pig ventricular myocytes using the whole-cell patch-clamp technique. Lactate at 20-40 mM in the internal solution activated ATP-sensitive potassium channels and shortened action potential duration. Activation of the channels occurred even in the presence of 2 5 mM ATP in the internal solution and was dependent on intracellular free magnesium levels. Our results suggest that intracellular lactate may play a significant role in activating cardiac ATP-sensitive potassium channels and shortening action potential duration even at ATP levels similar to those resulting from moderate to severe myocardial ischemia. PMID- 1939663 TI - Quantitative determination of different apolipoprotein B containing lipoproteins by an enzyme linked immunosorbent assay: apo B with apo C-III and apo B with apo E. AB - A non competitive enzyme-linked immunosorbent assay (ELISA) for total apolipoprotein (apo) B, apo B with apo C-III (LpC-III:B), and apo B with apo E (LpE:B), was developed. Microtiter plates were used as solid-phase, and subdivided into three parts, coated respectively with affinity purified antibodies to apo B, to apo C-III and to apo E. After incubating the antigen with coated plates, a horseradish peroxidase-labelled antibody to apo B was added to all the plates to estimate total apo B, LpC-III:B and LpE:B. PMID- 1939664 TI - Use of flagellin-enriched antigens in a rapid, simple and specific quantitative enzyme immunoassay for Lyme disease antibodies in human serum samples. AB - An enzyme immunoassay (EIA, ELISA) using microwells coated with a flagellin enriched fraction of B. burgdorferi and absorbent-containing sample diluent for the quantitative determination of Lyme disease (LD) IgG and IgM antibodies in human serum samples was described. This LD EIA required three 15-minute incubations at room temperature, followed by a 1-step normalization of photometer readings to EIA units (EU/ml). Compared with tests using the whole bacterial extract as antigens and a sample diluent containing 6% BSA, this new LD EIA revealed lower values for 20 syphilis (SS) and 21 normal serum samples (NS) but about the same for 21 Lyme disease (LD) samples, allowing lower cut-off points which would place almost all these SS and NS samples below while almost all LD samples above the positive cut-off point. The LD EIA results of larger numbers (67 to 291) of mixed samples correlated with results of four reference EIA. However, the LD EIA gave lower (2 to 4 fold) reactivities (index values) with SS and NS samples but higher values with positive serum samples than reference EIA. Thus, this LD EIA showed improvements in both specificity and sensitivity over other tests compared. PMID- 1939666 TI - Development of a highly sensitive enzyme linked immunosorbent assay for human serum progesterone using penicillinase. AB - A simple, highly sensitive, heterologous, competitive, penicillinase based tube ELISA for human serum progesterone has been developed. Specific antisera against progesterone was raised in rabbits using 11 alpha - hydroxyprogesterone hemisuccinate-BSA. Progesterone-3-CMO was coupled to penicillinase by the carbodiimide method. The standard curve covered a wide range from 5 pg/tube to 800 pg/tube. The sensitivity of the assay was 3.8 pg/tube. The intrassay coefficient of variation ranged from 8.6% to 11.2% at low concentration while at medium and high concentrations it ranged from 5.3% to 8.9%. The interassay coefficient of variation for the low, medium and high concentrations of progesterone were 9.6%, 10.7% and 6.5% respectively. Parallelism between the standard curve and the sample dilution curve indicated accuracy of the assay. Samples measured by RIA and ELISA showed an excellent correlation (r = 0.98). PMID- 1939665 TI - A sensitive immunoassay for von Willebrand factor. AB - We have developed an ELISA specific for canine von Willebrand factor antigen (vWF:Ag) that also strongly reacts with the VWF:Ag of humans and many other vertebrates. This assay was designed to avoid the use of immunoreagents of human origin, however, commercially available antibodies to human vWF:Ag may also be used. von Willebrand factor (vWF) was quantitated using a modified double sandwich ELISA with polyclonal antibodies specific for canine vWF:Ag. The assay was as sensitive for measuring canine vWF:Ag as previously published immuno radiometric assays and the most sensitive ELISA for human vWF:Ag. Employing commercially available antibodies to human vWF:Ag in the same double-sandwich configuration, the lower limit of detection for human vWF:Ag was 4.8 x 10(-6) units/ml, lower by a factor of ten than previously reported ELISAs. In addition, a wide range of vWF:Ag levels can be determined with just a single plasma dilution. The assay readily distinguishes type III von Willebrand disease from other types of von Willebrand disease having very low levels of vWF. This vWF ELISA can be used to evaluate large numbers of plasma samples simultaneously and is therefore well-suited for large-scale screening programs. PMID- 1939667 TI - Production and characterization of monoclonal antibodies reactive with melatonin. AB - Monoclonal antibodies(moAbs) reactive with melatonin(MT) were produced using MT, coupled to bovine serum albumin(BSA) with the Mannich reaction, as immunogen and conventional hybridoma techniques. Hybridoma clones secreting the moAbs were selected by an enzyme-linked immunosorbent assay system using MT carboxymethylchitin and BSA as screening antigens. The moAbs from 6 clones were characterized by a cross-reactivity test using radioimmunoassay with 125I labelled MT. The moAbs recognized MT but hardly recognized other analogues except for N-acetylserotonin with a crossreactivity of 0.81%. An inhibition curve for MT was obtained in the range of 50 pg to 100 ng and 1.4 ng of MT inhibited the value of the assay by half. There is interference from some unknown source in human serum. PMID- 1939668 TI - Application of a sol particle immunoassay to the determination of affinity constants of monoclonal antibodies. AB - The affinity constants (Ka) of monoclonal antibodies (MAb) for binding to their corresponding antigens (Ag), unlabelled and in buffered solution were determined by the following procedure: 1. Incubation of MAb (fixed concentration) with Ag (concentration dilution series). 2. Rapid bound/free separation by adding immobilized second antibody, followed by centrifugation. 3. Determination of free Ag in the supernatant using a gold sol particle agglutination immunoassay (SPIA) in a microtitration plate format. 4. Calculations and interpretation were based on Scatchard and Sips plots. Ka values found by this procedure were found to be similar to those obtained by a radio-immunoassay (RIA) procedure. The present method avoids possible artefacts in Ka values introduced by the procedure or chemical modification due to labelling of MAb or Ag. It enables rapid, simultaneous screening of a considerable number of different MAbs under non specialized (i.e. RIA) laboratory conditions. PMID- 1939669 TI - Vascularized cranial bone grafts for mandibular and maxillary reconstruction. The parietal osteofascial flap. AB - The authors have performed 13 cases of vascularized cranial bone grafts for reconstruction of maxillofacial defects since 1986. Two types of flaps were used: the parietal osteofascial flap pedicled to the parieto-temporal fascia based on the superficial temporal artery and the temporalis osteomuscular flap pedicled to the temporalis muscle based on the deep temporal artery. Zygomatico-orbital complex, maxilla and mandible were reconstructed and hemifacial microsomia was also treated. The results of vascularized cranial bone grafts pedicled to fascia were as good as those of grafts pedicled to muscle. There were no major complications. Two types of vascularized cranial bone grafts seem to be useful in reconstruction of maxillofacial defects with avascular recipient beds because of their good blood supply. The parietal osteofascial flap has additional advantages including easy rotation of the flap to the defect, particularly a mandibular defect, and versatile use of fascia without bulkiness for reconstruction of soft tissue defects. This flap can be designed as a full- or partial-thickness cranial bone graft with good vascularity. In this paper, our technique for mandibular and maxillary reconstruction using the parietal osteofascial flap is introduced, and the results compared with our temporalis osteomuscular flap technique are reported. PMID- 1939670 TI - Osteosynthetic titanium mini-plate fixation of composite radial forearm flaps in mandibular reconstruction. AB - This paper describes the evolution and refinement, over a four-year period, of a simple technique for shaping and stabilising the bony component of a composite radial forearm free flap to reconstruct the mandible following segmental resection for neoplastic disease. The results of reconstruction in 30 consecutive patients are reported. The current method of adapting and stabilising the radial bony strut using a specially designed 32 hole osteosynthetic miniplate is described. PMID- 1939671 TI - Frontal cephalometric evaluation of transverse dentofacial morphology and growth of children with isolated cleft palate. AB - The transverse dentofacial morphology and growth of 64 children operated on for clefting of the hard and soft palate was studied by means of a frontal proportional cephalometric analysis and was compared to a normal sample at the ages 3-4, 8-9 and 12 years. The cross-sectional comparison of the cleft palate and normal samples at the three periods indicated: (a) The presence in the cleft group of significantly increased ratios of the inner orbital width to the interorbital width and of the width of the nasal cavity to the interorbital width; (b) the absence of any significant differences in the ratio of the maxillary intermolar width to the interorbital width; and (c) the presence of almost identical ratios of the intergonial width of the mandible to the interorbital width and of the width of the maxilla to the intergonial width of the mandible. Evaluation of the changes of all cephalometric variables during the period 8-12 years showed the absence of any significant difference between the cleft palate and normal groups. PMID- 1939672 TI - The significance of an erroneous recording of the centre of mandibular rotation in orthognathic surgery. AB - The effect of post-operative jaw position of an error in locating the true centre of mandibular rotation was evaluated using a computer-simulation model and a mock surgery model. The centre of the condyle serves as a reference point in surgical procedures involving the maxilla. The purpose of this study was to describe the amount of malpositioning of the jaws at surgery due to a discrepancy between a simulated true centre of rotation and the centre of the condyle. The results showed, that a 20 mm error in location of the true centre of rotation could result in a 3 mm horizontal malpositioning of the maxilla. PMID- 1939673 TI - Acinic cell carcinoma of the salivary glands. A review of 20 new cases. AB - Twenty patients with acinic cell carcinoma of the salivary glands are presented. Seventeen tumours were located in the parotid and three in minor salivary glands, one being considered intraosseous. According to the growth patterns, they were classified as solid-acinar in 8 patients, microcystic in 5 patients, follicular in 3 patients and papillocystic in 4 patients. 9 cases were considered high grade malignant tumours and among the 11 well-differentiated, 2 suffered dedifferentiation in local recurrences. Local recurrence appeared in 9 cases. Three cases had nodal disease on admission while 5 developed this during the course of the disease. Distant metastasis appeared in 2 cases. Local recurrence and nodal disease correlated with the degree of differentiation and state of the margins in the surgical specimen. We recommend an aggressive surgical approach followed by postoperative radiotherapy for the undifferentiated tumours and extensive ones. For the limited and better differentiated, a more limited excision, such as total parotidectomy preserving the facial nerve is suggested. PMID- 1939674 TI - Ameloblastic carcinoma. Report of an aggressive case and review of the literature. AB - Odontogenic carcinomas of the jaws are classified as malignant ameloblastoma, ameloblastic carcinoma or primary intraosseous carcinoma. Because these lesions are extremely rare, microscopic diagnosis is difficult. An aggressive case of ameloblastic carcinoma of the mandible is presented. In spite of radical surgery and radiotherapy, the patient expired eight months following initial diagnosis. - A review of the literature seems to indicate that so called simple ameloblastomas rarely can dedifferentiate and metastasize following multiple inadequate surgical procedures. Although radical surgery is not necessary, local excision should be thorough. - Ameloblastic carcinoma and primary intraosseous carcinomas may be histogenetically similar. They are highly malignant tumours which should be treated aggressively. Metastasis is common and prognosis is poor. PMID- 1939675 TI - Mucormycosis in an apparently normal host. Case study and literature review. AB - Mucormycosis refers to an opportunistic fungal infection most often related to predisposing conditions, especially uncontrolled diabetes. It can occur as a rapidly extending rhinocerebral infection presenting a high mortality rate. The same micro-organism has, however, been identified in benign paranasal infections in the absence of a general debilitating condition, suggesting that host factors are of the utmost importance in the outcome of paranasal mucormycosis. PMID- 1939676 TI - Attention deficit hyperactivity disorder: does cognitive behavioral therapy improve home behavior? AB - This study evaluates the effectiveness of cognitive behavioral therapy (CBT) in improving the home behavior of children with attention deficit hyperactivity disorder (ADHD). Twenty-five boys (age 7 to 13) with a diagnosis of ADHD were randomized to a CBT or supportive therapy control group. Outcome measures included parent and teacher ratings of the child on the Behavior Problem Checklist-Attention Problem Subscale (BPC-AP), and the Self-Control Rating Scale (SCRS), parent ratings on the Modified Werry Weiss Activity Scale, and child ratings on the Piers Harris Self-Concept Scale and Matching Familiar Figures Task. Data were analyzed using a two-way analysis of variance for main effects. A significant improvement favoring CBT was found on the Werry Weiss Scale, which measures the parent's perception of the child's hyperactivity in the home, and the child's rating of his/her self-esteem on the Piers Harris Self-Concept Scale. Other outcome measures did not demonstrate statistical differences. This research provides support for the use of CBT in children with ADHD. CBT was found to improve the parent's perception of the child's hyperactivity in the home as well as the child's self-esteem. PMID- 1939677 TI - Teaching developmentally disabled children with chronic illness to swallow prescribed capsules. AB - Child noncompliance with prescribed medical regimens, including nonacceptance of oral medication, frequently impedes medical treatment and achievement of clinical aims. During this study, we used a single-subject experimental design to evaluate the effectiveness of a capsule-swallowing training curriculum specifically developed to promote acceptance of oral medication by multihandicapped children. Four such children participated, each diagnosed with a chronic pediatric illness requiring daily intake of oral medication. Training consisted of verbal instruction, demonstration, reinforcement for swallowing candies/capsules progressively larger in size, ignoring mild inappropriate behavior, and gradually providing less guidance and structure. In each case, the curriculum produced routine independent swallowing of prescribed capsules/tablets. Follow-up assessments, coupled with parent satisfaction ratings, suggest that skill acquisition was both enduring and clinically significant. This study validates a brief, readily exportable, and effective approach to teaching handicapped children to swallow capsules. PMID- 1939678 TI - Perceptions of medical compliance in children and adolescents with cystic fibrosis. AB - One hundred patients aged 5 through 20 years with cystic fibrosis, their parents, and their physicians were interviewed to assess patients' perceptions of compliance with prescribed treatments. Measures included self-administered questionnaires and the Medical Compliance Incomplete Stories Test. It was hypothesized that age-related differences in perceived compliance would be found and that such perceptions would vary as a function of four sociobehavioral factors (perceived severity of illness, optimism, level of independence in medical therapy, and degree of knowledge/understanding of illness). In addition, it was anticipated that the relationships between perceived compliance and the sociobehavioral factors would vary with age. Support for each hypothesis was found. Perceived compliance was related to age, with younger children showing greater perceived compliance to the medication regimen. Better perceived compliance was found to be associated with higher levels of optimism and child knowledge of the disease. Age differences in relationships between perceived compliance and optimism and child knowledge were found. Developmental implications for practice and future research are suggested. PMID- 1939679 TI - Evaluation of developmental/behavioral training in primary care. AB - Primary care and regular track residents in one pediatric program were compared with respect to knowledge, perceived level of competence, and attitudes relative to developmental and behavioral pediatrics from beginning to end of the residency. Measures of knowledge and self-perception of competence showed a common pattern characterized by (1) no differences between primary care and regular track residents on entry into the program, (2) significant progress in both groups over the period of the residency, (3) significantly greater progress by primary care residents. Ratings regarding relevance of developmental and behavioral issues for pediatric practice showed that ratings of relevance were significantly higher at the beginning of the residency among primary care residents and remained higher throughout. PMID- 1939680 TI - Effects of formula change on intestinal hydrogen production and crying and fussing behavior. AB - To determine whether incomplete carbohydrate absorption plays a role in mediating the effects of formula change on babies' crying, breath hydrogen excretion and behavior were measured in 17 normal formula-fed infants who entered a feeding trial at 28 days of life. The trial permitted two comparisons between (1) lactose and reduced lactose soy-based formulae, and (2) the infant's usual pretrial formula and the subsequent soy-based variable-carbohydrate formulae. Reduced lactose formula was associated with a small reduction in H2 excretion (from a mean of 15 to 7 ppm, p = .07) but no difference in crying or fussing. However, compared with their usual pretrial formula, the change to soy-based variable carbohydrate formulae was associated with a substantial and sustained reduction in H2 excretion (mean 32 to 11 ppm, p less than .03) and a modest 21% decline in fussing (90.4 to 71.5 min/24 hr, p less than .08). By 8 days after the formula change, there was a 40% decline (90.4 to 53.9 min/24 hr) in fussing. These results suggest that, although behavioral changes due to differences in carbohydrate content are unlikely in normal infants, formula changes involving protein and carbohydrate can reduce colonic gas production and may have some effect on crying. Such effects may be implicated when feeding changes occur in normal infants, but their potential role in treatment of crying problems (colic) is yet to be demonstrated. PMID- 1939681 TI - The effect of a multidisciplinary team approach on weight gain in nonorganic failure-to-thrive children. AB - Failure-to-thrive (FTT) is a chronic symptom accounting for 1% of all patients admitted to pediatric hospitals. FTT, which is traditionally attributed to organic (OFTT) and/or nonorganic (NFTT) causes, results in undernutrition. Undernutrition has potentially serious effects on child development, behavior, and cognitive skills. We undertook a study of children with FTT to determine whether multidisciplinary team treatment resulted in improved weight gain compared with children treated in a primary care setting. Fifty-three children with NFTT referred to our outpatient FTT consultative clinic and 107 children with NFTT identified as comparison subjects from our primary care clinic (PCC) were enrolled in the study. Growth outcomes over a 6-month follow-up were analyzed using growth quotient (GQ) analysis. Children followed in the multidisciplinary team clinic grew better (GQ = 1.75 +/- 0.39 SD) than did children in the PCC (GQ = 1.18 +/- 0.42 SD, p less than .001). The use of a multidisciplinary team offers special advantages in the rapid correction of undernutrition in children with NFTT. PMID- 1939682 TI - Failure-to-thrive: lessons from animal models and developing countries. AB - To better understand the complex associations between undernutrition and poverty in determining behavioral outcome for infants with failure-to-thrive (FTT), we have reviewed findings from research in undernutrition among animal models and among children in developing countries, where rates of infant undernutrition are extremely high. The associations among undernutrition, poverty, and family functioning persist in both animal and human research, whether manipulated in laboratory settings or observed in natural settings. Although environmental support and stimulation appear to ameliorate many of the negative consequences associated with undernutrition, infants with a history of nutritional deprivation are at increased risk for behavioral and emotional problems. Recommendations for prevention and intervention follow an ecological framework and include adequate access to food, knowledge of nutritional requirements and feeding approaches, support for parents and families, and a nurturant environment for infants. PMID- 1939683 TI - Neonatal bilirubin exposure and psychoeducational outcome. AB - The association between neonatal bilirubin exposure and psychoeducational outcome was investigated in a group of grade school children 9 to 11 years old who required neonatal intensive care between 1977 and 1980. Seventy-four children were evaluated with four measures of psychoeducational outcome, including the Kaufman Mental Processing and Achievement Scales, the Beery Visual Motor Integration Test, and the Vineland Adaptive Behavior Scale. A measure of bilirubin binding calculated directly from the albumin concentration correlated significantly with the Kaufman Mental Processing Composite, although other more direct measures of bilirubin exposure (such as maximum serum bilirubin, direct measures of binding, and cumulative bilirubin exposure) did not. Thus, it is possible that the impact on psychoeducational outcome is the result of some other effect of low serum albumin itself, in addition to its ability to bind bilirubin. The correlation of the calculated albumin-determined binding value with the Kaufman Mental Processing Composite suggests that this level, rather than total serum bilirubin, may be more appropriate in determining clinical management. PMID- 1939684 TI - Learning disabilities and school problems in a regional cohort of extremely low birth weight (less than 1000 G) children: a comparison with term controls. AB - We compared the prevalence of learning disabilities at age 8 years in a subgroup of 68 of 129 (53%) regional cohort of extremely low birth weight (ELBW) children who were considered "normal" neurologically and intellectually (IQ greater than or equal to 85) with that of 114 term group matched controls (C). Both groups were tested with a battery of psychoeducational measures, and parents and teachers completed questionnaires on the school performance of the children. ELBW children were comparable with C on measures of intelligence (ELBW 101 +/- 8, C 104 +/- 11), language, and academic achievement but fared significantly less well in motor performance (p less than .0001). The prevalence of learning disabilities (by predefined criteria) in ELBW children (26%) was not increased compared with C (19%). However, teachers rated significantly more ELBW children as performing below grade level than were C (31% vs 16%, p less than .05), and by parent report, a higher proportion of ELBW children had received special assistance in school compared with C (37% vs 16%, p less than .001). We conclude that although the prevalence of learning disabilities in normal ELBW children was not different from that in controls, ELBW children did less well and utilized more special resources. PMID- 1939685 TI - Early genital naming. AB - To evaluate the clinical impression that young girls are given little or confusing information about their genitals, a sample of 117 mothers with 1- to 4 year-old children were asked which words for genitals, if any, they used with their children. The ethnically and socioeconomically heterogeneous sample was composed of 63 girls and 54 boys, with the average ages of 26 and 29 months, respectively. Neither boys nor girls were likely to be given a standard anatomical genital term, although many children received colorful colloquial expressions. However, girls were less likely than boys to receive a term for their genitals. Receiving names for genitals was related to certain family circumstances, such as higher parental education, exposure to adult male nudity, having a sibling of the opposite sex, and cosleeping. Pediatric health professionals have the opportunity to contribute to early sex education by conveying accurate information regarding genital terms in the course of routine physical examinations. PMID- 1939686 TI - Teaching pediatric residents about child maltreatment. AB - Child maltreatment is a growing problem faced by pediatricians; however, there are many deficiencies in pediatricians' relevant knowledge and skills. Residency programs typically have included limited teaching in the area of child maltreatment. Fifty pediatric residents participated in an evaluation of a model educational course in child maltreatment developed by an interdisciplinary faculty. The course resulted in significant short-term improvements in knowledge and skills as well as a greater sense of competence in managing cases of child maltreatment. The importance of teaching pediatric residents about the "new morbidity" is discussed. PMID- 1939687 TI - Treatment of infant sleep disturbance by trimeprazine in combination with extinction. AB - Chronic sleep disturbance is a common problem in preschool children. Prescription and non-prescription sedatives provide short-term palliative relief. Behavioral extinction by withdrawal of parental attention is enduringly effective but may be distressing short-term because of postextinction bursts of intense activity by the child. This study evaluated the effects of combining extinction and sedative medication (trimeprazine tartrate), prescribed in a reducing dose over the first 10 days of extinction. Control groups received either extinction alone or a placebo administered double-blind. After baseline, all subjects reduced their sleep disturbance to low levels, the extinction and placebo groups declining slowly, the medication group abruptly. These gains were maintained at follow-up. Measures of infant security and maternal anxiety showed improvements with treatment. PMID- 1939688 TI - Children with phenylketonuria: the interface of family and child functioning. AB - Functioning and coping of 43 families with children with phenylketonuria (PKU) was investigated. A significant positive correlation was found among perceived family cohesion, dietary adherence associated with metabolic control, and child IQ. Parental education also significantly related to dietary adherence and to higher IQ level in the child. In addition, paternal perception of family adaptability was related to the child's IQ. Child depression as perceived by the parents was related to family functioning and coping variables. Functioning of PKU families is discussed in relation to current theories of family functioning under stress. PMID- 1939689 TI - Central auditory processing in the school-aged child: is it clinically relevant? PMID- 1939690 TI - Latent variable path analysis in clinical research: a beginner's tour guide. AB - Latent variable path analysis (LVPA) is undoubtedly one of "the" new statistical techniques being used increasingly often by clinical researchers. Although well suited for some types of clinical research, LVPA can be a somewhat intimidating technique for novices. This work is intended to provide a non-mathematical introduction to the advantages and problems of LVPA for clinical researchers who are not yet familiar with this powerful procedure. The conceptual bases of LVPA, its relation to other statistical techniques, and possible uses and misuses in clinical research are considered. Many practical recommendations for the appropriate use of LVPA also are offered, as is a suggested reading list for researchers who wish to learn more about LVPA and related approaches. PMID- 1939691 TI - The reasons for living inventory and a college population: adolescent suicidal behaviors, beliefs, and coping skills. AB - The suicidal behavior of a college population (N = 205) was assessed. Individuals were categorized into four groups: never suicidal, brief suicidal ideation, serious suicidal ideation, and parasuicidal. They also answered questions about why they would not choose suicide, on the Reasons For Living (RFL) Inventory. Depression, hopelessness, and social desirability scales also were presented. A significant difference existed between suicidal and nonsuicidal individuals on the RFL. Hopelessness and depression were found to be correlated significantly with suicidal behavior; social desirability was found to be high among those who were not suicidal and declined as suicidal behaviors became more severe. PMID- 1939692 TI - Narcissism and the use of fantasy. AB - This study examined the relationship between narcissism and the use of daydreams and fantasy in samples of 129 and 193 subjects. In sample 1, it was found that (1) narcissistic individuals experience achievement, heroic, sexual, hostile, self-revelation, and future-oriented daydreams; and (2) these six types of daydreams represent a coherent "narcissistic" fantasy style. In sample 2, narcissistic individuals who were experiencing higher levels of daily stress report using more self-admiration, power and revenge, and suffering fantasies to cope with stress. The narcissistic theme of entitlement is uniquely related to narcissistic fantasy and the narcissists' use of sustaining fantasies to cope with stress. Results are consistent with clinical literature on the narcissistic personality. PMID- 1939693 TI - Depression and engagement in pleasant and unpleasant activities in normal children. AB - This study investigated Lewinsohn's reinforcement model of depression by examining the relationship between depressive symptomatology and mood-related activities in normal children. Subjects were 138 children aged 8 to 14 years. Children and their parents rated the children's depression and engagement in pleasant and unpleasant activities. It was found that children's depression was correlated positively with increased engagement in unpleasant activities. However, the predicted negative correlation between children's depression and engagement in pleasant activities was supported only when children's mood was assessed by parental report, and not by children's self-report. PMID- 1939694 TI - Assessment of schizophrenic inpatients with the MCMI. AB - The Million Clinical Multiaxial Inventory (MCMI) Psychotic Thinking scale previously was found insensitive in the detection of schizophrenia. The MCMI also was shown to be susceptible to undetected "faking good." We hypothesized that the insensitivity of the MCMI Psychotic Thinking scale was due to an unwillingness of schizophrenic patients to report psychotic symptoms. The MCMI was administered to 258 male schizophrenic inpatients who were classified as symptom-reporters or nonreporters based upon whether they endorsed psychotic symptoms on a separate problem checklist. Willingness to report psychotic symptoms was a significant factor in MCMI Psychotic Thinking scale scores as well as many other MCMI scales. PMID- 1939695 TI - A short form of the Mississippi Scale for Combat-Related PTSD. AB - At the present time, The Mississippi Scale for Combat-Related PTSD (Mississippi Scale) is the best paper-and-pencil measure of this disorder. This study carried out a test-retest reliability on 52 chronic Vietnam veterans with PTSD and established three psychometric criteria for item retention in order to establish a short form of the Mississippi Scale. Ten items met these criteria and had a test-retest reliability coefficient of .66 (under the most stringent of conditions, treatment). This 10-item measure (Miss-10) then was applied to 95 new PTSD cases. This scale yielded two factors, guilt and numbing/anger. Discussion addressed its use as part of a screening battery or for monitoring change across time. PMID- 1939697 TI - Reading difficulty of MMPI-2 subscales. AB - Average reading difficulty based upon the Lexile value was computed for the 567 items and 61 sub/special scales of the MMPI-2. The mean for all items was 600.02 (SD = 304.57), which roughly corresponds to a fifth-grade reading level. Approximately 90% of the items require less than a ninth-grade reading level; 3 items require a high-school education or more. The Amorality (Mal) subscale had an average reading level greater than eighth grade. Nine subscales had 25% or more items above an eighth-grade reading level. The Hypomania (MA) subscales were the most demanding. For persons with low reading proficiency, interpretation of the nine subscales should be made cautiously. PMID- 1939696 TI - Reliability and validity of the Florida Sexual History Questionnaire. AB - The Florida Sexual History Questionnaire (FSHQ) is a brief 20-item questionnaire designed to assess male sexual dysfunction. The validity and reliability of the scale were examined in 33 diabetic impotent males and 58 nondiabetic, age equivalent nonimpotent males. The FSHQ was found to have high internal consistency and split-half reliability and significantly discriminated between nonimpotent and impotent subjects. Among diabetic impotent subjects, some of the test items were correlated significantly with physiological measures of sexual functioning. However, the FSHQ failed to discriminate between diabetics diagnosed as having organic or psychogenic impotence. This latter finding is discussed within the context of recent suggestions that it may not be possible to draw a clear dichotomy between organic and psychogenic impotence. PMID- 1939698 TI - Reliability and validity of the Mini-Mental State Exam in neurologically intact elderly. AB - Reliability and validity of MMSE were explored in a sample of 122 healthy, community-residing elderly volunteers between the ages of 57 and 85, who were tested with a battery of neuropsychological tests over three annual probes. Test retest reliability ranged between .45 and .50 over a 1-year interval and was .38 over a 2-year period. Change on the MMSE of more than 5 points over a 2-year period was associated with a neurological disorder. Significant correlations were found with many neuropsychological measures, especially with a measure of verbal learning. PMID- 1939700 TI - Analysis of WAIS-R factor patterns by sex and race. AB - Factor analyses of WAIS-R standardization data for samples grouped by sex and race (Black-White) produced congruent factors for the various samples and offered good support for Wechsler's two-scale division of the subtests. The factor structures for males and females produced some interesting differences across the age range that were related to sex-related findings in studies of patients with unilateral brain damage. Additionally, Black males and Black females seemed to use different strategies for solving Wechsler's verbal and nonverbal subtests. PMID- 1939699 TI - Intellectual loss in Alzheimer's dementia and WAIS-R intrasubtest scatter. AB - Patterns of intrasubtest scatter in the WAIS-R protocols of patients (n = 32) with Alzheimer's disease were compared to those of normal elderly controls (n = 32). The Alzheimer's patients showed more randomly dispersed item failures on some subtests, but normal controls showed more intrasubtest variability on other measures. Rates of correct diagnostic classification based on scatter measures were only slightly better than chance despite the presence of prominent anomia, memory impairment, construction apraxia, and significant decline from premorbid intellectual level in demented patients. In contrast, demographically based estimates of intellectual loss produced accurate diagnostic classification in 81% of the cases. The incremental validity of qualitative scatter analysis in the evaluation of suspected Alzheimer's disease appears to be minimal. PMID- 1939701 TI - Estimating WAIS-R IQ from the Shipley Institute of Living Scale: a replication. AB - Zachary, Crumpton, and Spiegel (1985) introduced a linear regression and continuous norming procedure for estimating Full Scale WAIS-R IQ from the Shipley Institute of Living Scale. The present study replicated their method with 55 adult psychiatric inpatients and day hospital patients. A high correlation (r = .85), an extremely small mean difference in IQ (.8 points), and an acceptable average absolute difference (7.6 points) were found between estimated and obtained WAIS-R. Sines and Simmons tables (1959) for Shipley estimates of WAIS IQ produced a high correlation (r = .86), but large mean and average absolute differences (13.1 and 13.6 points, respectively). The study supports use of the Zachary et al. procedure for estimating WAIS-R IQ from Shipley scores in a psychiatric population. PMID- 1939702 TI - A comparison of borderline and mild mental retardates assessed on the memory for designs and the WAIS-R. AB - A matched group (N = 114) between high errors and no error conditions on the MFD was examined in a population of borderline and mild mental retardates. Matched variables were sex, Full Scale IQ, and age. The MFD, PIAT, and the WAIS-R were administered to all subjects. Results on achievement tests showed that the mild mental retardation subjects with high errors on the MFD had lower achievement scores on the PIAT compared to the non-error group. The non-error group performed at a higher level on the Picture Arrangement, Vocabulary, Math, and Reading Comprehension. Borderline retardation subjects showed no significant differences between error and non-error groups on the PIAT and WAIS-R. These conclusions indicate that the MFD is a more sensitive indicator of intelligence differences than of organicity differences. PMID- 1939703 TI - Self-esteem, internal-external locus of control, and their relationship to weight reduction. AB - One hundred sixteen women participated in a 10-week weight reduction program and lost on the average of 7 kg. Family-related variables and two personality constructs, self-esteem and Internal-External Locus of Control (I-E Loc), were examined as predictors for success in weight loss. Principal findings were: (a) Subjects with low self-esteem scores lost significantly less weight than subjects with medium and high scores (4.3 kg vs. 8.7 and 6.4, respectively); (b) No significant differences were recorded between Internals and Externals with regard to weight reduction; and (c) Family-related variables, marriage and number of children, did not directly affect weight loss, but their effect was observed within the three self-esteem and the two I-E Loc groups. PMID- 1939704 TI - Self-acceptance, acceptance of others, and SYMLOG: equivalent measures of the two central interpersonal dimensions? AB - After 50 hours of small group participation during 9 weeks, 91 young adults rated each same-group member's conduct on SYMLOG's dimensions of dominance, friendliness, and task-orientedness. Earlier, they made similar ratings twice, several weeks apart, on separate measures of self-acceptance and acceptance of others. Individuals' mean SYMLOG dominance ratings by group peers correlated much more highly with aggregated ratings for self-acceptance (.83) than for other acceptance (.02), while SYMLOG friendliness correlated more positively with acceptance of others (.85) than with self-acceptance (.05). Self-ratings yielded parallel, but weaker associations. After attenuation corrections, these divergent approaches to assessing the interpersonal domain's central dimensions yielded empirically equivalent results. Both methods provide measures relevant to small group processes. PMID- 1939705 TI - Irrational beliefs, perceived availability of social support, and anxiety. AB - Based on the assumption that individual difference factors can influence aspects of the social environment, it was predicted that individuals who exhibit high levels of irrational beliefs would appraise their interpersonal environment as less supportive than would individuals with lower levels of irrational beliefs. The second prediction was that irrational beliefs would be related positively to anxiety. Thirdly, it was expected that perceived social support would be related inversely to anxiety. The final prediction was that deficits in social support among individuals who exhibit irrational beliefs may account, in part, for their relatively high levels of anxiety. Results based on questionnaire data obtained from 39 college students supported all four hypotheses. PMID- 1939706 TI - The assessment of involvement in role playing. AB - Two experiments (N = 169) focused on involvement in role playing. Subjects rated their level of involvement after each enactment; in addition, a probe procedure was used with prompts, increasingly disparate from the content of the role play. In the first experiment, subjects role played an anger of sad scenario; both measures of involvement correlated with emotional response, but were not correlated with each other. In the second experiment, involvement was manipulated experimentally; both measures varied as expected with the manipulation. PMID- 1939707 TI - The Exner Rorschach: an analysis of its clinical validity. AB - Data from Exner's 1985 and 1989 normative samples on nonpatient adults and comparison samples of patients with schizophrenia, depression, and character problems were reanalyzed using a standard of clinical significance appropriate for N = 1. The 1989 norms, which exclude Rorschach protocols with less than 14 responses, alter not only the number of significant variables, but also alter the ability of most variables that relate to form quality to differentiate among the patient comparison groups. The Exner Rorschach is judged to be a valid test for schizophrenia, but to have demonstrated little differential utility for depression and character disorders. It is recommended that the scoring of nonsignificant variables be abandoned. PMID- 1939708 TI - The influence of depressive symptomatology on alcoholics' locus of control: a methodological note and a correction. AB - In a previously published experiment from our laboratory, we reported two findings. First, controls showed the expected negative correlation between internal and external LOC dimensions, while alcoholics did not. Second, a difference score between LOC-internal and LOC-external was correlated significantly and positively with alcoholics' abstracting impairment. Data from two new independent samples of alcoholics and controls confirmed the first finding, but not the second; further, a calculation error was discovered in the previously published data that invalidated the second result. However, in all three studies, depressive symptomatology was found to be correlated negatively with the internal-external LOC difference score in both alcoholics and controls. It is suggested that depressive symptomatology be assessed in any study that investigates LOC. PMID- 1939709 TI - Adolescents, the MMPI, and the issue of K correction: a contemporary normative study. AB - Current adolescent norms for the MMPI are based on data obtained 25 to 45 years ago, from samples established in 1947 to 1957 and 1964 to 1965 (Marks & Briggs, 1967). Recently, MMPIs from 1,315 normal adolescent females and males, aged 13 through 17 years, were gathered from a three-state midwest area. There were significant differences between contemporary adolescent MMPI response patterns and those obtained from the earlier adolescent samples. This article presents new K-corrected normalized T-score conversion tables to encourage research that compares the relative efficacy of profiles calculated with and without K correction. PMID- 1939710 TI - The CAL: an MMPI alcoholism scale for general medical patients. AB - We developed a MMPI alcoholism scale based on adult medical patient samples. Our criterion group consisted of 736 inpatients (525 males; 211 females) diagnosed as having alcoholism according to DSM-III criteria. Three contrast samples that totaled 13,120 individuals were used for control purposes. MMPI items were chosen by means of logistic regression. The 33 items yielded by this procedure formed a provisional scale (CAL, for common alcoholism logistic) that worked equally well for males and females. With new cross-validation samples, with sensitivity (proportion of alcoholics correctly identified) set at 90%, the specificity (proportion of nonalcoholics correctly identified) ranged from 90% to 96% for selected contrast samples. We conclude that this scale shows promise as a screening device in similar populations. PMID- 1939711 TI - Comparisons among children's responses to the Hand Test by grade, race, sex, and social class. AB - Four hundred sixty-four children in grades K-8 of an urban school were tested in order to develop norms, check for the presence of developmental trends, and compare the performance of different demographic groups on the Hand Test. Comparisons across grade, race, sex, and socioeconomic class indicated that separate norms for grades, but single norms for race, sex, and socioeconomic levels are appropriate for elementary school children. Discrepancies in the developmental trends raised concern about the validity of indices of psychopathology especially as they apply to children in grades K-8. PMID- 1939712 TI - Concurrent validity between the California Psychological Inventory-revised and the Student Adaptation to College Questionnaire. AB - The present study examined the concurrent validity of the newest version of the California Psychological Inventory (CPI) with the Student Adaptation College Questionnaire. The sample consisted of 142 college students at a midwestern, technically oriented university. Significant differences in the expected directions were found between higher and lower adjusted students with regard to Gough's (1987) new control (p less than .001), flexibility (p less than .003), and consensuality (p less than .005) factors and also with respect to the new norm-favoring (p less than .01) and self-realization (p less than .008) thematic vectors of the revised CPI. PMID- 1939713 TI - Depression and personality disorder: differential diagnosis with the MMPI. AB - This study assessed the effectiveness of the MMPI in differentiating four clinically relevant types of depression. MMPI profiles of 53 subjects with major depression and personality disorder, 44 subjects with other depression and personality disorder, 27 subjects with major depression without personality disorder, and 20 subjects with other depression without personality disorder were compared via MANOVA, high-point pair analysis, and discriminant analysis. The instrument was found somewhat effective in differentiating the groups at a statistically significant level, but the differences were too subtle to be considered clinically useful. Thus, while the MMPI has some usefulness in the differential diagnosis of depression, it is best used in conjunction with other test data and relevant historical data. PMID- 1939714 TI - A neuropsychological screening battery for emergency assessment of carbon monoxide-poisoned patients. AB - The Carbon Monoxide Neuropsychological Screening Battery (CONSB) was developed to improve the neurological assessment of CO-poisoned patients in an emergency setting. Traditional assessment methods (clinical examination and carboxyhemoglobin [CoHb] levels) readily can identify unconscious, severely involved patients; however, many CO-intoxicated patients with cerebral impairment who also require aggressive hyperbaric oxygen therapy are assessed inadequately by such methods. Administration of the CONSB to 66 CO-poisoned patients and 66 volunteer controls revealed significant differences in performance between the two groups. It was concluded that the CONSB enhanced the accuracy of the evaluation of cerebrally impaired CO-poisoned patients. Failure to assess the cerebral functioning of patients exposed to CO and to identify those who require aggressive oxygen therapy could have neurological sequelae. PMID- 1939716 TI - The construct validity of the Multidimensional Aptitude Battery: a word of caution. AB - Results of an hierarchical factor analysis with university students (N = 101) do not support the construct validity of the Multidimensional Aptitude Battery (MAB). Although the MAB Full Scale IQ seems to be a valid measure of general mental ability, the construct validity of the Verbal and Performance scale IQs is not supported. Therefore, the Verbal and Performance IQs should be interpreted with caution, if at all. In addition, re-analysis of previous investigations of the MAB underscores the importance of ascertaining the reading level of subjects prior to the administration of the MAB. Marginal reading proficiency, especially on a timed paper-and-pencil test such as the MAB, will confound results. PMID- 1939715 TI - Major depressives' and dysthmics' performance on the Wisconsin Card Sorting Test. AB - Despite awareness that depression may affect performance on commonly used neuropsychological tests, little research has been conducted on the relative impact of severity and type of depression on higher problem-solving ability. Major depressives (n = 13), dysthymics (n = 17), and non-psychiatric comparison subjects (n = 18) were administered the Wisconsin Card Sorting Test (WCST). Although diagnostic category was related only marginally to some WCST measures after controlling for intellectual function, depressive symptom severity emerged as an independent predictor of Total Errors, Perseverative Responses, and Failure to Maintain Set. These findings lend support to the suggestion that neuropsychological test batteries should include assessment for depression and suggest that even relatively mild depression may affect WCST scores. PMID- 1939717 TI - Predictive validity of two short-forms of the WPPSI: a 3-year follow-up study. AB - An equally weighted WPPSI short-form (Comprehension, Arithmetic, Block Design, and Picture Completion) was administered to 64 prekindergarten children, while a verbally weighted WPPSI short-form (Comprehension, Arithmetic, Block Design, and Vocabulary) was administered to 63 prekindergarten children. All subjects subsequently were administered school achievement tests at the end of the first- and second-grade years. Low, but significant correlations between the FSIQ and achievement test scores were obtained; the Arithmetic and Block Design subtests were the best subtest predictors of school achievement in grades one and two. The predictive validities of the two WPPSI short-forms were found to be essentially equivalent. PMID- 1939718 TI - Clinical features of eating disorders and individual psychological functioning. AB - Relationships between the clinical features of eating disorders and individual psychological functioning were investigated in a population of 114 eating disordered females, which consisted of 63 bulimics, 9 anorexics, 7 bulimic anorexics, 23 with eating disorders not otherwise specified, and 12 with indications of an eating disorder, but without sufficient data for further differential diagnosis. No significant differences in psychological functioning were found when diagnosis was used to classify the subjects into groups, but significant differences did emerge when subjects were classified by specific clinical features. Among the clinical features associated with greater psychopathology were: low body weight, frequent weight fluctuations, amenorrhea of longer duration, purging via laxatives, frequent exercising, and more frequent binges of longer duration. PMID- 1939719 TI - Personality dimensions reflected by the Rorschach and the 16PF. AB - This study examined the relationships between Rorschach variables and the 16PF in a sample of 62 university students. Good form level was associated with ego strength, and Popular responses were associated inversely with a scale of rebelliousness. The results did not support some hypotheses, for example, that the Difference score, inanimate movement, and diffuse shading would correlate with 16PF indicators of good coping. On the contrary, the Difference score was associated with a scale that suggests anxiety. Further examination revealed that EA, M, and M+ also were associated with 16PF scales of guilt and anxiety. FC+, T, and to a lesser extent S, were associated with indications of good, relatively anxiety-free functioning. PMID- 1939721 TI - What is codependency? AB - This article examines the rapidly developing codependency movement and appeals to psychologists to investigate this area systematically. An effort is made to clarify factors that have contributed to confusion about the meaning of codependency, and an argument is made for the use of operationally defined diagnostic criteria. Literature is reviewed on both dependency and codependency, and important differences between these two concepts are discussed. Cermak's (1986) proposition that codependency be added to the Diagnostic and statistical manual of mental disorders--revised (DSM-III-R; American Psychiatric Association, 1987) as an Axis II personality disorder also is considered. Research possibilities and clinical applications are explored in the areas of assessment and treatment and in considering the comorbidity of codependency with psychological and physical disorders. PMID- 1939720 TI - Verbal fluency deficits in female alcoholics. AB - Verbal fluency deficits in female alcoholics (n = 48) were investigated using Thurstone's Word Fluency Test (TWFT) and a category fluency test. Overall, alcoholics performed less well than did controls (n = 36). Simple effects indicate that although controls performed less well on category fluency than on the TWFT, alcoholics did not differ between the two tests. Simple effects also show that controls' performance was superior to that of alcoholics on the category fluency test, but the groups did not differ on the TWFT. The pattern of results suggests that the process of shifting rapidly between categories is more difficult than perusing a mental lexicon. Correlations between these tasks and other tests of cognitive functioning suggest that the TWFT and the category fluency test may be assessing different types of verbal fluency. PMID- 1939722 TI - Whither high technology? PMID- 1939723 TI - An evaluation of two signal-processing hearing aids. AB - Various forms of signal processing are used in modern ASP hearing aids. The present study investigated the relationship between sentence recognition ability and two types of signal processing used in commercially available hearing aids. Results indicated a significant improvement in sentence recognition ability employing an instrument with adaptive compression (variable release time) versus an instrument with an adaptive high-pass filter with short attack and release times. Data were obtained for a single-talker competing message at several message-to-competition ratios. The adaptive compression system may prove to be beneficial to hearing-impaired listeners in certain background noise environments. PMID- 1939724 TI - Toward implementation of a flexible hearing aid measurement system. AB - An evaluation of a computerized hearing aid measurement system was performed with input and output compression hearing aids stimulated using high-quality audio equipment. The results of the computer measurements were compared to those from a manual technique using conventional laboratory instrumentation. The results from the computerized and manual methods matched very closely. However, the computer system was found to be considerably more flexible than conventional instrumentation and was much easier to use. PMID- 1939725 TI - Simulating reflex induced changes in the acoustic impedance of the ear. AB - A simple procedure for measuring changes in the acoustic impedance of the ear is described. The technique has several applications, including simulation using a standard coupler of changes in real ear impedance produced by the acoustic reflex. The technique has also been used for calibrating the response time of an otoadmittance meter used in measuring the temporal characteristic of reflex activity. PMID- 1939726 TI - Evaluation of a dereverberation technique. AB - A two-microphone dereverberation technique was evaluated by obtaining speech recognition measures and preference judgments from normal-hearing and hearing impaired listeners. Monaural speech recognition performance was measured for two reverberation conditions (0.4 second and 1.2 seconds) with and without processing. Binaural speech recognition performance was also measured for the unprocessed conditions. In addition, paired-comparison judgments of preference were obtained for all combinations of the processed and unprocessed monaural stimuli. For both groups of subjects, scores at the shorter reverberation time were significantly higher than scores for the longer reverberation time. For the normal-hearing subjects, processing to dereverberate had no significant effect on speech recognition performance. Binaural presentation of the unprocessed signal yielded significantly higher scores. For the hearing-impaired subjects, performance was significantly better in the unprocessed condition than the processed condition, but was not significantly different from the binaural condition. Paired-comparison judgments revealed differences in patterns of preference between normal-hearing and hearing-impaired listeners. PMID- 1939727 TI - The problem of feedback in hearing aids. AB - One of the factors that limits hearing-aid performance is feedback. This paper discusses the problem of feedback in hearing aids, illustrated with examples based on a computer simulation of hearing-aid behavior. The available technology for dealing with the problem of feedback is then reviewed, and new digital signal processing approaches are described that may finally solve the feedback problem. PMID- 1939728 TI - Continuous discourse tracking: an analysis of the procedure. AB - The method of continuous discourse tracking was evaluated in terms of the strategies used by the talker and the types of responses elicited from the listener. Talker utterances were classified into four categories: 1. Complete repetition (of the initial utterance); 2. Partial repetition; 3. Repetition with change in emphasis; and 4. A combined strategy using two or more correction strategies. Listener responses were classified into three categories: 1. Correct repetition of intended utterance; 2. Partially correct repetition; and 3. Totally incorrect repetition or no response. The listeners showed small but statistically significant differences in their response patterns. Much larger differences were observed in the pattern of correction strategies used by the talkers. Differences in correction strategy were also observed between the early and later stages of a talker-listener exchange. PMID- 1939729 TI - Immunohistochemical localization of calretinin in the rat hindbrain. AB - The localization of calretinin in the rat hindbrain was examined immunohistochemically with antiserum against calretinin purified from the guinea pig brain. Calretinin immunoreactivity was found within neuronal elements. The distribution of calretinin-immunoreactive cell bodies and fibers is presented in schematic drawings and summarized in a table. Major calretinin-immunoreactive neurons were found in the lateral and medial geniculate nuclei, substantia nigra, ventral tegmental area, interpeduncular nucleus, periaqueductal gray, mesencephalic trigeminal nucleus, superior and inferior colliculi, pontine nuclei, parabrachial nucleus, dorsal and laterodorsal tegmental nuclei, cochlear nuclei, vestibular nuclei, medullary reticular nuclei, nucleus of the solitary tract, area postrema, substantia gelatinosa of the spinal trigeminal nucleus, and cerebellum. These results show that distinct calretinin-immunoreactive neurons are widely distributed in the rat hindbrain. PMID- 1939730 TI - Ultrastructural evidence that early synapse formation on central vestibular sensory neurons is independent of peripheral vestibular influences. AB - Migration and early differentiation of neurons of the tangential vestibular nucleus of the chick take place between embryonic days 5 and 8. In the absence of primary vestibular afferents (otocyst-ablation), a previous light microscope study documented that early developmental events still occurred, but the neurons failed to complete differentiation and to survive. In order to understand why these neurons undergo normal early development, we have repeated the vestibular deafferentation paradigm followed by ultrastructural observations on these neurons. We found that the ultrastructural events associated with migration and differentiation in the deafferented tangential nucleus were essentially normal from 5 to 8 days. Most important, longitudinal fibers, presumably of central, nonvestibular origins, formed the first synapses at the same time and sequence as observed in normal embryos. Thus vestibular sensory neurons receive their first input from central fibers, initiating events in the formation of a central vestibular circuitry without the influence of peripheral vestibular fibers or endorgan. PMID- 1939731 TI - Organization of the histaminergic system in the brain of the teleost, Trachurus trachurus. AB - To accumulate phylogenetic information on the central histaminergic system, we investigated the histaminergic system in the brain of a teleost, the jack mackerel (Trachurus trachurus), using the indirect immunofluorescent method with antiserum against histamine. A small number of histamine-immunoreactive cell bodies were observed in the posterior hypothalamus around the posterior recess. Histamine-immunoreactive fibers innervated the telencephalon, diencephalon, tegmentum, and rostral part of the medulla oblongata. The immunoreactive fibers were very sparse or absent in the olfactory bulb, optic tectum, cerebellum, caudal part of the medulla oblongata, spinal cord, and hypophysis. Ascending fiber bundles were seen in the basal hypothalamus, supplying fiber collaterals to the telencephalon and diencephalon, whereas descending fibers were observed in the midline of the lower brainstem. These findings suggest that the central histaminergic system of the jack mackerel is homologous to those of mammals, reptiles, and amphibians, although poorly developed compared with them. The histamine-immunoreactive neuronal cell bodies found in the border area between the mesencephalon and rhombencephalon of the river lamprey were not detected in the brain of the jack mackerel. PMID- 1939732 TI - Myelo- and cytoarchitecture of the granular frontal cortex and surrounding regions in the strepsirhine primate Galago and the anthropoid primate Macaca. AB - As the first part of a comparative investigation of primate frontal cortex, we compared the frontal architectonic organization of Galago, a small-brained, strepsirhine (or "prosimian") primate, to that of an anthropoid primate, Macaca, by using myelin- and Nissl-stained material. We were able to distinguish many more areas in both taxa than have been recognized in most previous studies of the primate frontal lobe. In particular, we were able to subdivide many of the areas shown in the commonly cited architectonic map of Walker (J. Comp. Neurol. 73:59 86, 1940). Delineation of areas was greatly facilitated by the use of the Gallyas technique for staining myelin. The areal organization of much of frontal cortex (specifically, the premotor, orbital, and medial regions) appears to be very similar in Galago and Macaca. In these regions, we were able to recognize the same complement of areas in both taxa, with few exceptions. In the granular frontal cortex (GFC), by contrast, we were able to distinguish about twice as many areas in Macaca as in Galago. For most of the GFC areas of Galago, there are architectonically similar areas in Macaca; the areas shared by both taxa correspond mainly to the arcuate and superior areas of Macaca (i.e., the region encompassed by Walker's areas 45, 8A, and 8B). However, there are many additional, more rostral, areas in Macaca for which there are no obvious homologues in Galago. In particular, Galago lacks cortex resembling the distinctive, lightly myelinated cortex of the Macaca principal sulcus (Walker's area 46 and its subdivisions). Our results are difficult to reconcile with the view that frontal lobe organization varies little across taxa. Rather, they suggest that granular frontal cortex underwent considerable change during primate evolution, including the addition of new areas in anthropoids. PMID- 1939733 TI - Architectonics of the parietal and temporal association cortex in the strepsirhine primate Galago compared to the anthropoid primate Macaca. AB - A number of higher order association areas have been described in the parietal and temporal cortex of large-brained anthropoid primates such as Macaca. However, little is known about the evolution of these areas, and the existence of homologous areas has not yet been clearly demonstrated in other mammalian groups. We addressed this issue by comparing the myelo- and cytoarchitecture of posterior association cortex in the anthropoid Macaca to that of the small-brained, strepsirhine ("prosimian") primate Galago. Our results suggest that Galago possesses many, if not most, of the areas present in Macaca. We were able to identify regions in Galago which resemble Macaca posterior parietal area 7, superior temporal polysensory cortex (ST), inferotemporal visual cortex (IT), the temporoparietal auditory area (Tpt), and posterior parahippocampal cortex (areas TH and TF). Area 7, ST, and IT can each be subdivided further in Macaca, and for most of these subdivisions we were able to identify counterparts in Galago. However, we could not distinguish as many divisions of ST cortex in Galago as in Macaca, and it is possible that new areas arose in this region during anthropoid evolution. There also appear to be general differences in architectonic organization between these animals, with Macaca exhibiting greater development of pyramidal layer IIIc and of the internal granular layer (IV) across much of the parieto-temporal cortex. These findings suggest that many, although possibly not all, of the parietal and temporal association areas present in the modern anthropoid Macaca evolved early in primate history, prior to the divergence of the lineages leading to strepsirhines and anthropoids. PMID- 1939734 TI - Distribution of FMRFamide-related peptides in the blood-feeding bug, Rhodnius prolixus. AB - Immunohistochemistry was used to study the distribution of FMRFamide-like material in the central and peripheral nervous systems and visceral tissues of 5th instar Rhodnius prolixus. Over 200 immunoreactive cell bodies and their processes as well as extensive neuropile regions were distributed throughout the nervous system. Immunoreactive processes were seen over the cephalic aorta, corpus cardiacum/corpus allatum complex, and in neurohaemal sites on the abdominal nerves. In visceral tissues, immunoreactive processes were seen innervating the salivary glands, the foregut, and the hindgut. Immunoreactive cells were also found in the anterior midgut (i.e., the crop and the anterior intestine). A radioimmunoassay specific for "RFamide" carboxy-terminal peptides was used to quantify the amount and the distribution of FMRFamide-like material. Reversed-phase high performance liquid chromatography of nervous tissue extracts revealed several peaks of immunoreactive material. The results suggest the existence of a number of FMRFamide-related peptides in Rhodnius which may have roles in both central and peripheral transmission, may be released as neurohormones and may have endocrine functions in the gut. PMID- 1939735 TI - Development of the rabbit retina: II. Muller cells. AB - Muller (glial) cells of the rabbit retina were stained with antibodies against the intermediate filament protein vimentin in retinal wholemounts from various developmental stages. Both the density of stained profiles and the mean diameter of these profiles were measured, with the microscope focus in the inner plexiform layer of the retinae. Within this retinal layer, every Muller cell possesses one stout vitread process; thus counts of the stained profiles allow an estimation of their number. After postnatal day (P) 9, the total number of stained cells was slightly above 4 million per retina; for the adult rabbit retina, this agrees well with earlier data obtained by our group based on another method, as well as with published data from other groups. We suggest that after P 9, only Muller cells are stained, and this population is numerically stable. In contrast, neonatal retinae contained significantly more stained profiles. This indicates that either the total number of Muller cells is reduced by "physiological cell death" or that additional cells are stained neonatally. We discuss why we favour the second possibility. After P 9, two peculiarities occur in the Muller cell population: (1) their density decreases gradually, to a greater extent in the retinal periphery than in the center (i.e., in the "visual streak"), and (2) Muller cell diameters increase, again more in the periphery than in the center. We argue that differential retinal expansion leads to dispersion of the pre existing cell population and allows for widening of the Muller cell processes. We conclude that Muller cells can be used postnatally in the rabbit retina as "landmarks" of expansion. PMID- 1939737 TI - Effect of cooling rate on the survival of frozen wood frogs, Rana sylvatica. AB - Wood frogs (Rana sylvatica) were frozen to -2.5 degrees C under five distinct cooling regimes to investigate the effect of cooling rate on survival. Frogs survived freezing when cooled at -0.16 degrees C.h-1 or -0.18 degrees C.h-1, but mortality resulted at higher rates (-0.30 degrees C.h-1, -1.03 degrees C.h-1, and -1.17 degrees C.h-1). Surviving frogs in the latter groups required longer periods to recover, and transient injury to the neuromuscular system was evident. Some of the frogs that died had patches of discolored, apparently necrotic skin; vascular damage, as indicated by hematoma, also occurred. It is concluded that slow cooling may be critical to the freeze tolerance of wood frogs. Additional studies examined the effect of cooling rate on physiological responses promoting freeze tolerance. Mean glucose concentrations measured in plasma (15-16 mumol.ml 1) and liver (42-45 mumol.g-1) following a 2-h thaw did not differ between slowly and rapidly-cooled frogs but in both groups were elevated relative to unfrozen controls. Thus, freezing injury to rapidly-cooled frogs apparently was not mitigated by the presence of elevated glucose. Water contents of liver tissue, measured 2 h post-thawing, did not differ between slowly-cooled (mean = 77.6%) and rapidly-cooled (mean = 78.5%) frogs. However, the mean hematocrit of slowly cooled frogs (48%) was significantly higher than that (37%) of frogs cooled rapidly, possibly owing to differences in the dynamics of tissue water during freezing. PMID- 1939736 TI - Sexually dimorphic distribution of neurotensin/neuromedin N mRNA in the rat preoptic area. AB - Neurotensin release from estrogen-responsive neurons in the rostral preoptic area of the female rat may play an important role in triggering preovulatory secretion of gonadotropin-releasing hormone on proestrus. We investigated the possibility of sexually differentiated biosynthesis of neurotensin in the rostral preoptic area, using in situ hybridization histochemistry to detect neurotensin/neuromedin N (NT/N) mRNA in adult male rats and adult female rats at proestrus and the first day of diestrus. In sections through the anteroventral periventricular nucleus (AVPv), the number of labeled cells in proestrous females was four times that in males. Diestrus females exhibited half the number of labeled cells present at proestrus, and there was evidence for a significant correlation between circulating estradiol level and number of labeled cells in the AVPv. In the rostral portion of the medial preoptic nucleus (MPN), two contiguous groups of labeled cells were especially prominent. One group, in the medial half of the MPN, was located closer to the midline in females than in males and displayed greater labeling in males than in females. Furthermore, labeling in the rostral MPN was greater at proestrus than at diestrus. These results indicate that biosynthesis of neurotensin and neuromedin N in the rostral preoptic area may be sexually differentiated and, in the female, may vary across the estrous cycle in parallel with circulating estradiol levels, consistent with the view that neurotensin neurons in this area are involved in the regulation of preovulatory secretion of gonadotropin-releasing hormone. The sex- and region-specific expression of NT/N mRNA in the rostral preoptic area suggests functional heterogeneity of neurotensin neuronal populations in this area and implies complex regulation of NT/N gene expression in the rat brain. PMID- 1939738 TI - Circulation, metabolic rate, and body size in mammals. PMID- 1939739 TI - Measurement of branchial vascular space of trout, Oncorhynchus mykiss: effects of adrenaline. AB - Using the isolated-perfused head preparation at a constant flow rate, hemodynamic effects of adrenaline were studied in trout gills. The calculation of the vascular spaces was performed with the isotopic pulse technique allowing measurement of the distribution space of the tracer. The results show that the branchial arterial circuit was cleared more quickly than the branchial venous and cephalic circuits. Adrenaline addition significantly increased the volume of the branchial arterial circuit at the expense of the venous circuit, illustrating the closing of arterio-venous sphincters under catecholamine control. The increase of the arterial volume could be explained by a vasodilation of the arterial circuit, rather than resulting from lamellar recruitment. Furthermore, the flow rate of the cephalic circuit represented 5% of the total branchial flow rate. PMID- 1939740 TI - Effects of serum, its protein and lipid extracts, and commercial serum proteins and lipid on the isolated frog heart. AB - This study investigates the inotropic effects of serum, its protein and lipid extracts, and commercial serum proteins and lipid on the isolated, spontaneously beating heart and superfused, hypodynamic ventricle of the frog. Serum taken from either man, horse, calf, frog, or rabbit evoked marked positive inotropic responses which were unaffected by cholinergic, serotonergic, and adrenergic receptor antagonists. Dialysed serum (dialisand) and void volume fractions from Sephadex G200-120 columns corresponding to large molecular weight constituents evoked marked positive inotropic responses. When serum was separated into fractions containing either proteins or lipids/lipoproteins by high-density ultracentrifugation or activated charcoal, both extracts evoked marked positive inotropic responses. Commercial serum globulins and serum containing a high proportion of immunoglobulins elicited large increases in contractile force, whereas serum albumin evoked a negative inotropic effect. Serum which was either boiled and/or treated with chymotrypsin to denature proteins also caused a marked increase in isometric twitch tension in the frog heart. Similar inotropic response was obtained with fractions of boiled serum eluted on columns of Sephadex G200-120. These fractions corresponded to molecular weight in the region of 60-70 kDa. However, the inotropic effect of boiled serum was abolished following pretreatment with lipase. Superfusion of frog hearts with commercial cardiolipin resulted in marked dose-dependent increases in contractile force. The results demonstrate the presence of at least two large molecular weight cardioactive principles in serum. These substances are comparable in size to constituents of serum proteins (e.g., globulins and immunoglobulins) and serum lipids/lipoproteins (e.g., cardiolipin) and may serve as physiological regulators of cardiac function. PMID- 1939741 TI - Regulation of body temperature, metabolic rate, and sleep in fasting pigeons diurnally infused with glucose or saline. AB - To test the hypothesis that nocturnal body temperature (Tb) and metabolic rate (MR) in the pigeon are regulated during sleep at levels proportional to energy reserves, continuous recordings of Tb, oxygen consumption (VO2), carbon dioxide production, and electrophysiological measures were taken from five pigeons subjected to two separate 4-day fasts. Energy reserves were depleted differentially during the fasts by 12-h diurnal infusions of either saline or isosmotic glucose solutions. Although Tb and VO2 were closely correlated, VO2 declined throughout the fast during diurnal and nocturnal phases of the 12:12 light-dark cycle whereas significant declines in Tb were restricted to the night. Diurnal thermal conductance declined over days of fasting, especially during saline infusions, and was reduced to minimal levels each night. The durations and distributions of arousal states did not change during the fast or differ between conditions. The results were consistent with the hypothesis of a nocturnal regulation of Tb and metabolic rate proportional to energy reserves. PMID- 1939742 TI - Defects in resting metabolic rates and mitochondrial respiration in Kwashiorkor and dietary obese rats. AB - Resting metabolic rates have been measured and compared with hepatic mitochondrial respiration in Kwashiorkor and diet-induced obese weaned rats. In Kwashiorkor, resting metabolic rate was 21% lower than the value of controls, while that of the obese rats was 14% higher than in control animals. The resting metabolic rate for Kwashiorkor animals was 50% of the predicted basal metabolic rate (BMR), whereas that of the obese rats was 23% higher than the predicted BMR. The mitochondrial oxygen consumption patterns, using malate plus glutamate or succinate as respiratory substrates, revealed that the resting respiration (state 4) was 23.9% higher in Kwashiorkor and 29.1% higher in obese animals, while the active (state 3) respiration was 34.8% lower in Kwashiorkor and 43.3% lower in obese rats compared to controls. The respiratory control ratios (RCR) were 51.1% and 43.8% in Kwashiorkor and obese rats, respectively, relative to the values in control rats. It is concluded from these studies that Kwashiorkor disease and diet-induced obesity appear to interfere with oxygen utilization at the level of state 3 mitochondrial respiration, which is markedly decreased when compared to the values for control animals. PMID- 1939743 TI - Adaptation of intestinal hydrolases to starvation in rats: effect of thyroid function. AB - The effects of long-term starvation on the activities of sucrase, lactase, and aminopeptidase, and on their respective mRNA were determined in the small intestine of thyroidectomized and sham-operated adult rats. Thyroidectomy reduced the protein loss at the level of the intestinal brush border membranes during starvation. Prolonged fasting caused a significant decrease in sucrase activity, but thyroidectomy partly prevented this effect. However, the amount of the corresponding mRNA dropped during long term starvation without incidence of thyroidectomy. Lactase activity in the brush border membranes was increased by starvation, and thyroidectomy caused a further elevation of the enzyme activity. Simultaneously, lactase mRNA content rose only slightly compared to the enzyme activity. Aminopeptidase activity and mRNA content decreased during starvation and thyroidectomy did not prevent this process. These results indicate that intestinal hydrolases respond non-coordinately to long-term food deprivation. In addition, the thyroid status of the animals has a direct influence on the adaptation of several brush border hydrolases to starvation. This suggests that the drop in plasma thyroid hormones during fasting allows a better maintenance of protein content and of hydrolase activities in the brush border membranes of the small intestine. These adaptive processes seemed to be partly controlled at a post-transcriptional level. PMID- 1939744 TI - A positive fever response in Agama agama and Sceloporus orcutti (Reptilia: Agamidae and Iguanidae). AB - Three species of lizards (Agama agama, Mabuya perrotetii, and Sceloporus orcutti) were tested for a possible increase in mean selected body temperature (MSBT) in response to intraperitoneal injection of alcohol-killed Aeromonas sobria, a gram negative bacterium known to be pathogenic to reptiles. A paired experimental design was utilized in which each animal was given an injection of sterile saline and 1.10(10) A. sobria. Body temperatures were monitored via indwelling cloacal thermocouples at 4-min intervals for one 12-h light period under saline injection and for two consecutive 12-h light periods under bacteria injection. Agama agama demonstrated a significant increase in MSBT on both day 1 and day 2 of bacteria injection with increases of 2.7 and 2.3 degrees C, respectively. The latency period on day 1 averaged 6.4 h. Sceloporus orcutti demonstrated a significant decrease in MSBT on day 1 of bacteria injection and a significant increase in MSBT of 1.0 degree C on day 2 of bacteria injection. No fever was evident in S. orcutti until the beginning of day 2. Mabuya perrotetii did not exhibit a significant change in MSBT on either day 1 or day 2 of bacteria injection. Agama agama (family Agamidae) is the first Old World reptile to exhibit a fever response to bacteria injection, and with these results fever has now been demonstrated in the lizard families Agamidae, Iguanidae, and Teiidae. PMID- 1939745 TI - Regulation of ion and water transport across the eel intestine: effects of acetylcholine and serotonin. AB - Both acetylcholine (ACh) and serotonin (5-HT) lowered the serosa-negative transepithelial potential difference (PD) and the short-circuit current (Isc), accompanied by a decrease in NaCl and water absorption across the eel intestine. These inhibitory effects of ACh and 5-HT were blocked by atropine, a muscarinic receptor antagonist, and ICS-205930, a 5-HT3 receptor antagonist, respectively. Even after blocking the ACh receptor with atropine, 5-HT inhibited the PD and Isc, and ACh lowered them after blocking the 5-HT receptor with ICS-205930, indicating that ACh and 5-HT act independently. Similar inhibition in the PD and the Isc was observed after electrical field stimulation (EFS) which is expected to release endogenous regulators. These effects of EFS were reduced by 70% after simultaneous addition of atropine and ICS-205930. Since atropine and ICS-205930 block ACh and 5-HT receptors, respectively, these results suggest that endogenous ACh and 5-HT are released by EFS. PMID- 1939746 TI - Short-chain fatty acids and CO2 as regulators of Na+ and Cl- absorption in isolated sheep rumen mucosa. AB - Unidirectional 22Na+ and 36Cl- fluxes were determined in short-circuited, stripped rumen mucosa from sheep by using the Ussing chamber technique. In both CO2/HCO3(-)-containing and CO2/HCO3(-)-free solutions, replacement of gluconate by short-chain fatty acids (SCFA, 39mM) significantly enhanced mucosal-to-serosal Na+ absorption without affecting the Cl- transport in the same direction. Short chain fatty acid stimulation of Na+ transport was at least partly independent of Cl- and could almost completely be abolished by 1 mM mucosal amiloride, while stimulation of Na+ transport was enhanced by lowering the mucosal pH from 7.3 to 6.5. Similar to the SCFA action, raising the PCO2 in the mucosal bathing solution led to an increase in the amiloride-sensitive mucosal-to-serosal Na+ flux. Along with its effect on sodium transport, raising the PCO2 also stimulated chloride transport. The results are best explained by a model in which undissociated SCFA and/or CO2 permeate the cell membrane and produce a raise in intracellular H+ concentration. This stimulates an apical Na+/H+ exchange, leading to increased Na+ transport. The stimulatory effect of CO2 on Cl- transport is probably mediated by a Cl-/HCO3- exchange mechanism in the apical membrane. Binding of SCFA anions to that exchange as described for the rat distal colon (Binder and Mehta 1989) probably does not play a major role in the rumen. PMID- 1939747 TI - The effect of corticosterone on standard metabolic rates of small passerine birds. AB - Resting metabolic rates of Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) and pine siskins (Carduelis pinus) were evaluated at thermoneutral temperatures before and after administration of corticosterone (B) at physiological doses. There was no effect of B on basal metabolic rate of either species, but nocturnal metabolic rate varied significantly less over the 3 h period of measurement in B-treated sparrows and siskins than in control birds. These results, coupled with observations of caged birds, suggest that corticosterone has no direct effect on avian resting metabolism but does reduce the responsiveness of birds to external stimuli and thus promotes nocturnal restfulness. PMID- 1939748 TI - MR and CT imaging of paraspinal textiloma (gossypiboma). AB - This report describes two cases of textiloma (gossypiboma, foreign body granuloma). These so-called "cottonoids" (Codman, U.S.A.) were inadvertently left behind in the operation wound following spinal surgery for an intervertebral disk herniation. Both textilomas were located paraspinally. These relatively uncommon lesions should be differentiated from paraspinal tumors, as well as from other postoperative complications, such as scar formation. Although plain radiography generally gives a characteristic image due to a marking filament, the CT and especially MR findings are less well known. PMID- 1939749 TI - MR and CT in the evaluation of sarcoid myopathy. AB - Sarcoid myopathy is a relatively rare extrapulmonary complication of sarcoidosis. We evaluated the diagnostic utility of MR at 1.5 T in four patients with sarcoid myopathy of the lower extremities established by biopsy. Two of the patients were of the "atrophic type" and two of the "nodular type." The findings on MR were compared with the findings on CT, gallium scanning, and electromyography. Only MR was positive in all cases. The T2-weighted scans (spin echo 2,000/80) revealed two distinctly different patterns of abnormality (i.e., discrete foci of high signal intensity lesions in the patients with the nodular type of sarcoid myopathy and atrophic muscle of high signal intensity in the patients with the atrophic type). Due to its ability to provide objective findings of the extent and distribution of muscle involvement, MR should prove useful in the detection, diagnosis, and monitoring of sarcoid myopathy. PMID- 1939750 TI - MR imaging of periosteal chondroma. PMID- 1939752 TI - MR study of normal joint function using a low field strength system. AB - A functional MR study was performed using a 0.064 T permanent magnet MR system. The shoulder joints, elbow joints, hip joints, and knee joints of three volunteers (mean height and weight, 176 cm and 71 kg, respectively) were examined at incremental joint angles in three to eight stages during flexion-extension, abduction-adduction, or pronation-supination movement. Each set of 16 images was obtained in 4 min, 49 s using three-dimensional Fourier transformation methods with gradient echo pulse sequences. The images were evaluated in static mode and sometimes in cine mode. The findings obtained about the physiology of these normal joints was generally compatible with findings previously accumulated in the field of kinesiology. The study suggests that this method can be useful for in vivo study of kinesiology and pathogenesis of diseases and that patients with most types of contracture or deformity can be examined by MR imaging. PMID- 1939751 TI - MR of enchondroma and chondrosarcoma: rings and arcs of Gd-DTPA enhancement. AB - MR studies of five chondrosarcomas and three enchondromas were performed with intravenous Gd-DTPA administration. All tumors showed enhancement of scalloped margins and curvilinear septa (ring-and-arc pattern) on T1-weighted SE sequences with Gd-DTPA. On radiologic-pathologic correlation, the enhanced areas corresponded to fibrovascular bundles surrounding hyaline cartilage lobules. The rings and arcs of enhancement with Gd-DTPA on MR is a reflection of the lobulated growth pattern of cartilaginous tumors and therefore helpful in differential diagnosis of bone tumors. PMID- 1939753 TI - Giant cell tumors of bone containing large amounts of hemosiderin: MR-pathologic correlation. AB - We present three giant cell tumors of bone that contained large amounts of hemosiderin and compare their MR appearance with intraoperative findings and histological characterization. Histologically, hemosiderin was found in multinucleated giant cells, mononuclear stromal cells, and xanthoma cells. All cases showed markedly decreased signal areas on both T1- and T2-weighted MR imaging due to hemosiderin deposition; this made evaluation of the integrity of the adjacent cortices difficult. In one case, extraosseous tumor extension appeared as a signal void area on MR imaging. Findings on immunohistochemical studies suggested the giant cells may have a histiocytic nature. Because the tumor cells themselves have a phagocytic nature, the decreased signal areas in and around giant cell tumors should be regarded as active tumor tissues in delineating the tumor on MR imaging. PMID- 1939754 TI - MR imaging of cardiac mass in Wegener granulomatosis. AB - Wegener granulomatosis is a disorder of unknown etiology characterized by a necrotizing granulomatous vasculitis that primarily affects the paranasal sinuses, lungs, and kidneys. It is usually a disease of adults with infrequent cardiac involvement. We report the unusual presentation of this disorder in an adolescent with a cardiac mass. The findings on two-dimensional echocardiography and MR imaging are discussed. PMID- 1939755 TI - CT of nodular hyperplasia of the liver in non-Hodgkin lymphoma. AB - During follow-up of non-Hodgkin lymphoma in a 60-year-old man, multiple hepatic small lesions were incidentally found by sonography. Dynamic CT disclosed enhancing masses in both the right and left lobes and faint arterioportal shunting in the left lobe of the liver. These findings were confirmed by angiography. Portal hypertension was, however, not present. Exploratory laparotomy revealed nodular regenerative hyperplasia of the liver. The nontumorous liver was normal. PMID- 1939756 TI - Biliary cystadenoma with intratumoral bleeding: radiologic-pathologic correlation. AB - We report a case of a 35-year-old woman with a mucinous biliary cystadenoma of the liver. The patient presented with the acute onset of upper abdominal pain and jaundice, symptoms caused by bleeding into the cystadenoma. Findings of a variety of imaging modalities including ultrasound, CT angiography, MR imaging, and endoscopic retrograde cholangiopancreatography are correlated and verified by pathological studies performed on the material obtained surgically. PMID- 1939757 TI - CT of primary adrenal lymphoma. AB - We present a case of primary adrenal lymphoma with CT appearance of a cystic mass containing mural calcification. Sonographic findings are correlated. Comparison of imaging features is made with the few previously reported cases of this rare entity. PMID- 1939758 TI - MR diagnosis of subdiaphragmatic anomalous pulmonary venous drainage in a newborn. AB - Our report describes a case of infradiaphragmatic total anomalous pulmonary venous return diagnosed by MR in a newborn with an interruption of the aortic arch with ventricular septum defect and anomalous pulmonary venous drainage. The severity of the congenital cardiopathy did not permit surgical treatment and the infant died soon after. Pathology confirmed the MR findings. Magnetic resonance not only complements echocardiography but also can be used for patients in intensive care and can in our case avoid angiography. PMID- 1939759 TI - Percutaneous extraction of an osteoid osteoma of the lumbar spine under CT guidance. AB - We report one case of percutaneous extraction of an osteoid osteoma of the lumbar spine under CT guidance. We describe the procedure of nidus extraction. This technique allows precise removal of the nidus with pathologic verification after extraction. PMID- 1939760 TI - Blood-brain-barrier disruption in acute Wernicke encephalopathy: MR findings. AB - The clinical and MR features of an alcoholic woman with Wernicke encephalopathy are reported. During the acute stage Gd-diethylenetriamine pentaacetic acid enhanced MR revealed damage of the blood-brain barrier bilaterally and symmetrically adjacent to the third ventricle, cerebral aqueduct, and fourth ventricle. The enhancement disappeared after successful thiamine therapy, as demonstrated in a repeat postcontrast MR 1 week later. PMID- 1939761 TI - Thoracic meningocele in neurofibromatosis: CT and MR findings. AB - A case of lateral intrathoracic meningocele incidentally found in association with neurofibromatosis Type 1 is presented. Magnetic resonance imaging proved most valuable in diagnosis. PMID- 1939762 TI - Eccentric cystic facial schwannoma: CT and MR features. AB - Facial schwannomas are uncommon lesions with a fairly characteristic range of clinical and radiographic presentations. This report describes an unusual case of facial schwannoma that clinically and radiographically mimicked a cystic skull base lesion extrinsically compressing the facial nerve. The MR findings are presented. PMID- 1939763 TI - Fractured submandibular gland: CT findings. AB - A patient presented 12 h following trauma with a slowly expanding neck mass. Both CT and sialographic evaluation demonstrated a fracture of the left submandibular gland. PMID- 1939764 TI - Splenic hemangiomatosis: CT and MR features. PMID- 1939765 TI - Renocolic fistula with abscess masquerading as a renal cell carcinoma: CT findings. PMID- 1939766 TI - Double-echo MPGR imaging of the rotator cuff. AB - T2-weighted gradient recalled (T2*) sequences are often used in place of T2 sequences when imaging the shoulder. The main advantages of these sequences are the decreased imaging time, the better demonstration of cartilage disorders, and the added tissue information that can be garnered due to the increased sensitivity to magnetic susceptibility with T2* sequences. Unfortunately, one drawback of T2* sequences that is less apparent with spin-echo techniques is the sensitivity of tissue close to the surface coil to undergo diffusely increased signal throughout an area in close proximity to the coil (coil-burnout). This phenomenon is a very bothersome artifact that can obscure tissue differentiation in this area. Fluid detection, especially in the subacromial bursa, can be especially difficult to diagnose in the presence of coil-burnout. We describe MR imaging of the shoulder using double-echo T2-weighted multiplanar gradient recalled sequences, which allow better evaluation of shoulder pathology. PMID- 1939767 TI - Physiological effects of fast oscillating magnetic field gradients. AB - To evaluate the physiological thresholds of neuromuscular stimulation relevant to very fast NMR imaging studies that use gradient switching at frequencies of 1-2 kHz and a maximum magnetic field of up to 10 mT, a series of studies were done with human volunteers using an experimental echo planar gradient coil set. The threshold for induction of localized and momentary sensations in the human back and abdomen for 10 subjects is 60 T/s for sinusoidally oscillating magnetic fields at 1.27 kHz. The threshold relates to an E field of 6 V/m and is shown to vary with number of oscillations and frequency in accord with theory. Using a simple model of E field induction, the threshold for stimulation of cardiac electrical events should be greater than 4 times this value. PMID- 1939768 TI - Localized proton NMR spectroscopy of brain tumors using short-echo time STEAM sequences. AB - Recent progress in localized proton NMR spectroscopy has been utilized to improve the spatial resolution and the metabolic specificity in a study of 19 patients with intracranial tumors. Selected examples demonstrate that short echo time stimulated echo acquisition mode sequences are able (a) to account for macroscopic tissue heterogeneity by reducing the volume of interest to 2-8 ml and (b) to facilitate a reasonable characterization of tumor metabolism by increasing the number of accessible metabolites. Proton NMR spectra were acquired within measuring times of 6.5 min on a 2.0 T whole-body system using the imaging headcoil. PMID- 1939769 TI - MR color mapping of myelin fiber orientation. AB - Diffusion of water in brain white matter has been shown to be anisotropic: Water mobility is lower when measured perpendicular to the fiber direction rather than parallel to it. This feature was used to produce images of the myelin fiber orientation. Coronal and sagittal MR diffusion images were obtained in volunteers using an echo-planar imaging sequence sensitized to molecular diffusion in perpendicular directions. Color-coded images of myelin orientation were then generated by combining these images together. The orientation of the white matter tracts was found to be in excellent agreement with known anatomy. Myelin fiber orientation mapping may offer a new perspective to evaluate white matter disorders. PMID- 1939770 TI - Screening protocol for MR imaging of the internal auditory canal. AB - We have previously shown that 5 mm axial T1-weighted images following Gd diethylenetriamine pentaacetic acid (DTPA) administration were sufficient as a screening examination of the internal auditory canal (IAC) and cerebellopontine angle cistern in 80% of cases with sensorineural hearing loss. In the remaining 20% of cases 3 mm slices were necessary for confirmation of the diagnosis. To reduce the number of cases requiring the additional examination, we have modified our protocol to include a coronal "scout" T1-weighted sequence followed by 5 mm axial sections angled through the IACs. Routine axial T2-weighted images of the posterior fossa were also obtained. One hundred eleven patients were studied with this protocol. In all but two of these the 5 mm sections unequivocally provided the diagnosis and in those two cases the coronal images confirmed the diagnosis suspected on the axial study. Three millimeter slices were not necessary in any patient. This three sequence, post-Gd-DTPA protocol, which requires only 12 min of scan time, is recommended as a screening protocol for IAC and cerebellopontine angle disease. PMID- 1939771 TI - MR imaging of middle ear cholesteatomas. AB - We prospectively evaluated MR images of 14 patients who had chronic otitis media and who were suspected of having cholesteatomas on otologic examination and/or on high resolution CT. Cholesteatomas were verified in the middle ear and/or mastoid at surgery in nine patients. Cholesteatomas appeared isointense relative to gray matter on T1-weighted spin echo MR images (T1WI) and hyperintense on T2-weighted spin echo MR images (T2WI) in eight patients. Two cholesterol granulomas appeared hyperintense on both T1WI and T2WI. In three patients with chronic otitis media the associated mixed granulation tissue and fluid collection was revealed as nonspecific, heterogeneous signal intensity in two cases. In the third case the signal intensity was similar to that found in cholesteatomas. PMID- 1939772 TI - Pulmonary alveolar microlithiasis: CT findings. AB - We present five cases with confirmed diagnosis of pulmonary alveolar microlithiasis that illustrate the appearance of this rare chronic lung disease on conventional and high-resolution CT. Pulmonary alveolar microlithiasis is characterized by widespread intraalveolar calcification of both lungs. Conventional CT confirmed the inferior and posterior predominance of the lesions in four of our cases and showed an exceptionally high concentration of microliths in the subpleural parenchyma and along the bronchovascular bundles. High resolution CT revealed a perilobular and bronchovascular distribution of the disease process at the level of the secondary pulmonary lobule. This pattern correlated closely with pathologic findings. PMID- 1939773 TI - Wegener granulomatosis: CT features of parenchymal lung disease. AB - Chest CT from eight patients with pulmonary Wegener granulomatosis were reviewed. The CT features of parenchymal lung involvement included multiple nodules or masses (seven of eight; 88%), ranging in size from 0.3 to 5.0 cm. Lung nodules demonstrated distinct feeding vessels in seven of eight patients (88%); and lesions similar to pulmonary infarcts, i.e., peripheral wedge-shaped lesions abutting the pleura, were identified in seven cases (88%). Scarring, spiculation, and pleural tags emanating from pulmonary nodules were prominent features (seven of eight; 88%). Other findings included cavitation (four of eight; 50%), air bronchograms through nodules (two of eight; 25%), and pleural effusions (two of eight; 25%). One patient on immunosuppressant therapy also demonstrated scattered ground glass infiltrates due to complicating pneumocystis pneumonia. In comparison to corresponding conventional chest radiography, CT examinations revealed more parenchymal lesions in five of eight cases (63%) and bilateral disease instead of unilateral disease in one of eight cases (13%). Feeding vessels were only identified on CT. Wegener granulomatosis is a primary necrotizing granulomatous vasculitis, and when it affects the lung it demonstrates CT features that are similar to other vessel-related disorders of the lung such as septic emboli, pulmonary infarcts, and tumor emboli of hematogenous metastases. We believe that these CT features--nodules with feeding vessels and wedge-shaped lesions abutting the pleura--are related to the necrotizing angiitis that affects pulmonary arteries and veins in this disease. PMID- 1939774 TI - Cardiac tumors: assessment with Gd-DTPA enhanced MR imaging. AB - Previous studies have shown the value of MR imaging for the identification of cardiac masses. The distinction of intramural tumors from normal myocardium may be equivocal because of the similarity of signal intensity between tumor and normal myocardium on ECG-gated SE images. The purpose of this study was to assess the role of Gd-DTPA for improving the contrast between cardiac tumors and myocardium. Four patients with established or suspected cardiac tumors were imaged with a 1.5 T imager. The T1-weighted images (TR = RR interval, TE = 20-30 ms) were obtained before and immediately after the intravenous injection of Gd DTPA, at a dosage of 0.1 mmol/kg. Tumors were identified in three patients. All tumors were isointense to the myocardium in precontrast images but demonstrated differential enhancement relative to myocardium after the administration of Gd DTPA. Two tumors were hyperintense relative to myocardium, and the third was mostly hypointense, surrounded by a hyperintense rim. In the remaining case, no tumor was found and the myocardium was homogeneously enhanced on postgadolinium images. Gadolinium DTPA can produce differential enhancement of tumor from normal myocardium and therefore demonstrate intramural masses. PMID- 1939775 TI - Cardiac first-pass and myocardial perfusion in normal subjects assessed by sub second Gd-DTPA enhanced MR imaging. AB - To evaluate first pass in the right ventricular (RV) and left ventricular (LV) cavities and myocardial perfusion, subsecond MR imaging was performed in seven normal subjects following intravenous bolus injection of Gd-DTPA. After the baseline scans, sequential ECG-triggered images were obtained every three to four RR intervals. The procedure consisted of an initial presaturation pulse (150 degrees), and the acquisition time for one image was approximately 500 ms with 64 phase-encoding steps. After bolus administration of Gd-DTPA (0.05 mmol/kg body wt), progressively increasing signal intensities were observed in the RV cavity, the LV cavity, and the myocardial wall. Gadolinium DTPA enhanced subsecond MR offers temporal information of the first transit in the cardiac chambers and may provide useful clinical reference data for assessment of myocardial perfusion in patients with coronary artery disease. PMID- 1939777 TI - Preoperative 3D rendering of MR imaging in liver metastases. AB - In 15 patients who were to undergo resection of hepatic metastases, three dimensional (3D) images of the liver were rendered from axial T2-weighted MR images by a dedicated 3D workstation. This report assesses the utility of these images in preoperative planning and intraoperative guidance. In three patients, the preoperative 3D images convinced the surgeon of resectability. All patients had laparotomies and in 12 patients, in whom the liver lesions were evaluated, there was good to excellent spatial correlation. Intraoperatively, the 3D images aided the surgeon by allowing early detection of unresectability, by showing relationships of lesions to major vessels, and by directing the surgeon to lesions otherwise difficult to find. In two patients, the original MR images failed to show multiple small lesions, thus limiting the usefulness of the 3D images. PMID- 1939776 TI - MR imaging of the pancreas at high field strength: comparison of six sequences. AB - The authors compared six MR sequences comprising conventional breath-hold [rapid spin echo (RASE) repetition time (TR) 240 ms/echo time (TE) 8 ms/90 degrees, fast low angle shot (FLASH) 130/4.5/80 degrees, TurboFLASH 6.5/3.5/8 degrees], fat suppressed regular spin echo (FS SE 330/15/90 degrees), and two combined fat suppressed breath-hold sequences (FS FLASH 130/8/80 degrees, FS RASE 240/10/90 degrees) for studying the normal pancreas. Sequences were selected on the basis of features desirable for demonstrating the pancreas, particularly absence or decrease in artifacts and improved dynamic range of intraabdominal tissue signal intensities. Ten normal volunteers were studied, six at 1.5 T and four at 1.0 T, and comparison was made to regular short TR/TE SE. Quantitative pancreas signal to-noise (S/N) and pancreas fat-to-noise (SD/N) measurements and qualitative evaluation of overall resolution and artifacts were determined. Fat suppressed FLASH had the highest S/N (44.1 +/- 10.8, p less than 0.0001) and SD/N (35.0 +/- 11.9, p less than 0.0001), and seven studies were considered good or very good. Fat suppressed SE had good S/N (32.6 +/- 7.7) and SD/N (19.0 +/- 3.6), and eight FS SE studies were considered good or very good. Among the nonsuppressed sequences, FLASH had the best combination of quantitative and qualitative measurements. Our results suggest that fat suppression may be important for studying the pancreas and that nonsuppressed FLASH may be a reasonable alternative. PMID- 1939778 TI - Exercise-induced acute renal failure and patchy renal vasoconstriction: CT and MR findings. AB - Contrast-enhanced CT and MR imaging of the kidney were performed in two patients with acute renal failure and severe loin pain following a track race. Prior to the exercise both patients had had flu-like symptoms and took oral medications. There was no evidence of myoglobinuria. Immediate postcontrast CT of the kidney showed multiple patchy areas of poor contrast enhancement; after 24 h, there were multiple patchy enhancing cortical areas on CT without further use of intravenous contrast media. Magnetic resonance imaging of the kidney showed patchy areas of high signal intensity with obliteration of the corticomedullary contrast on T1 weighted images. On T2-weighted images the signal intensity of the lesion was high in one patient and low in the other. PMID- 1939779 TI - Spin-echo and STIR MR imaging of sports-related muscle injuries at 1.5 T. AB - Seventy patients with clinically diagnosed athletic muscle injuries of varying severity were studied with MR imaging at 1.5 T. Twenty underwent follow-up MR studies. In all cases, SE T1-weighted and double-echo T2-weighted pulse sequences were used. These were supplemented by short T1 inversion recovery (STIR) sequence in 36 cases. Muscle injuries were more readily seen with STIR images than with SE T2-weighted images. In both initial assessment and follow-up of tears, the use of the STIR technique allowed the greatest lesion/muscle contrast. Short TR, short TE SE images provided anatomic detail and were an adjunct to T2-dependent SE images in the evaluation of organized hematomas (11 cases). Follow-up MR studies in 20 patients at variable time intervals allowed demonstration of regression of the tear in 11 cases, fibrous scar formation in 5 cases, and recurrence of the tear in 4 cases. Evolution of hematomas into scar and into cyst was demonstrated in three and two cases, respectively. Owing to the additive effect of T1 and T2 mechanisms, the STIR sequence is well suited for initial evaluation and can replace T2-weighted images in the follow-up of muscle trauma. PMID- 1939780 TI - Classification of cutaneous squamous cell carcinoma. PMID- 1939781 TI - Microvenular hemangioma. AB - Ten examples of a distinctive vascular tumor are reported. These benign acquired lesions typically occur as small, enlarging lesions that favor the extremities, particularly the forearms, of young to middle-aged adults. Clinically, they are purple to red lesions generally thought to be hemangiomas. Histologically, there is a pattern of irregular, branching venules with inconspicuous lumina and lack of cellular atypia. Because the lesions do not conform to existing classifications of vascular tumors, they have been designated with the histologically descriptive name of microvenular hemangioma. Although speculative, they are felt to represent a form of acquired venous hemangioma. PMID- 1939782 TI - Dermatofibrosarcoma protuberans presenting in infancy and childhood. AB - Dermatofibrosarcoma protuberans (DFSP) is a not uncommon low-grade cutaneous sarcoma of uncertain histogenesis, which typically arises in early to middle adult life. Traditionally, it is regarded as extremely uncommon in infants and children, and this diagnosis may therefore easily be overlooked in young patients. Eight such cases (representing 5.9% of the available DFSPs on file) are presented of which two were congenital. Age range at presentation was 14 months to 12 years. Five arose on the trunk. Most had originally been mistaken for unclassified sarcoma, a fibromatosis, or diffuse neurofibroma. The histologic features were entirely comparable to the more usual adult cases except that all had a plaque-like, rather than nodular, growth pattern. Short-term follow up has revealed no recurrences. DFSP is not so rare in childhood and warrants wider recognition in order to ensure appropriate treatment. PMID- 1939783 TI - Morphogenesis of the cornoid lamella: histochemical, immunohistochemical, and ultrastructural study of porokeratosis. AB - To elucidate the morphogenesis of cornoid lamellae (CL) in porokeratosis, skin lesions of three cases of disseminated superficial actinic porokeratosis and a case of linear porokeratosis were examined. By N-(7-dimethylamino-4-methyl-3 coumarinyl)maleimide staining, SH groups were present in the living layer of the epidermis beneath CL and irregularly disappeared at the bottom of CL, whereas SS linkages appeared in dyskeratotic cells in the living layer and in the irregularly shaped cell membranes of the horny cells. Epidermis beneath CL showed an increased and irregular involucrin expression. Ultrastructurally, the living keratinocytes contained many cytoplasmic vacuoles and had a smaller number of lamellar bodies than normal. Intercellular lamellar sheets were incompletely formed. The dyskeratotic cells and the lower horny cells contained many small vacuoles but formed a marginal band. The horny cells of CL also formed a marginal band and, further, a keratin pattern. CL may be formed by hyperproliferative atypical kertatinocytes which keratinize rapidly and irregularly and show defective desquamation due to the paucity of intercellular lamellar sheets. PMID- 1939784 TI - HMB-45 staining of dysplastic melanocytic nevi in melanoma risk groups. AB - To evaluate the hypothesis that reactivity of the intradermal component of melanocytic nevi to the monoclonal antibody HMB-45 correlates with melanoma risk, dysplastic compound melanocytic nevi were examined for expression of the HMB-45 epitope in three subject groups differing in epidemiological risk for melanoma. The study groups consisted of 10 subjects with dysplastic nevi and a personal history of melanoma, 25 subjects with dysplastic nevi and a history of melanoma in one or more first degree relatives, and 15 population control subjects with sporadic dysplastic nevi. For each case, sections from one lesion, immunohistochemically processed for HMB-45 binding, were evaluated by two pathologists without knowledge of the clinical data. Of all dysplastic nevi, 98% showed diffusely positive cytoplasmic staining of the junctional nevomelanocytes and 90% had such positive staining of those cells within the superficial dermis. Nevus cells within the deeper dermis did not stain positively in any case. Furthermore, the data showed no differences in frequency, pattern, or intensity of HMB-45 reactivity between the subject groups. These observations indicate that evaluation of dysplastic nevi with the monoclonal antibody HMB-45, an apparent marker of proliferative or otherwise stimulated melanocytes, has no discriminating value for identifying subjects at increased historical risk for melanoma. The data, however, support the concept that so-called dysplasia within nevi, as defined by histologic criteria, actually represents the active or proliferative phase of melanocytic nevi. PMID- 1939785 TI - Analysis of HMB-45 immunoreactivity in common and cellular blue nevi. AB - HMB-45 is generally thought of as a melanoma specific antibody; however, there are certain exceptions. It is known that most dermal nevi show no reactivity; however, the dermal nevus component within dysplastic nevi and certain Spitz nevi show positive reactivity. In order to further examine this observation, we undertook a study to examine blue nevi, both common and cellular, for the expression of HMB-45. Cases were stained with antibodies directed at both HMB-45 and S100 protein. Of 16 common blue nevi studied, 14 were positive with HMB-45, as were 6 of 6 cellular blue nevi. Staining for HMB-45 was quite variable in intensity amongst cases labelled common blue nevi. In contrast, cellular blue nevi were uniformly strongly positive. It is therefore concluded that blue nevi, including cellular blue nevi, exhibit an activated phenotype as demonstrated by HMB-45 reactivity. PMID- 1939786 TI - Lack of evidence of Ki-ras codon 12 mutations in melanocytic lesions. AB - A number of studies have failed to detect point mutations at codon 12 in the Ki ras gene in melanocytic neoplasms. One recent study, however, has found a high percentage of Ki-ras codon 12 point mutations. In an effort to resolve this difference, the present study examined noncultured melanocytic lesions (i.e., 5 benign nevi, 10 dysplastic nevi, and 8 primary melanomas: 4 in situ and 4 invasive) for point mutations at codon 12 in the first exon of the Ki-ras proto oncogene using polymerase chain reaction methodology with oligonucleotide hybridization and direct DNA sequencing. The results of this study indicates no detectable mutations in the 12th codon of the first exon of the Ki-ras gene in any premalignant or malignant melanocytic lesion examined. PMID- 1939787 TI - Application of DNA flow cytometry from paraffin-embedded tissue to the diagnosis of mycosis fungoides. AB - The distinction of mycosis fungoides from benign inflammatory lesions is sometimes difficult by conventional histological techniques. Aneuploidy, a feature often associated with malignant tumors, can be assessed even in tissue routinely processed in paraffin using the flow cytometric technique of Hedley and associates. In many tumor systems, there are significant diploid clones. We have evaluated the flow cytometric DNA ploidy of paraffin-embedded tissue in the diagnosis and prognosis of mycosis fungoides (MF). We studied 22 cases of MF and 10 control cases of inflammatory skin lesions with epidermal involvement. Aneuploidy was found in 27% of the MF cases, but in none of the controls (ED). Aneuploid features were seen in 23% of tissues from early stage disease. Aneuploidy did not correlate with atypia, epidermotropism, or number of mitoses. There was a trend towards showing adverse outcome in those patients with aneuploid lesions. The detection of aneuploidy might be helpful for early diagnosis of MF. PMID- 1939788 TI - Keratoacanthoma within a superficial spreading malignant melanoma in situ. AB - A case of a keratoacanthoma arising from the center of a superficial spreading malignant melanoma in situ is presented. The keratoacanthoma already showed regressive changes in its central area, and the superficial spreading malignant melanoma had partially disappeared at the site in which the keratoacanthoma had arisen. The possible mechanisms of these interactions are discussed. PMID- 1939789 TI - Splendore-Hoeppli phenomenon in Pityrosporum folliculitis (pseudoactinomycosis of the skin). AB - Actinomyces-like granules showing the Splendore-Hoeppli phenomenon have been demonstrated in histologic material, e.g. uterine curettings, in various conditions unrelated to genuine actinomycotic infection. The exact nature of the granules and the mechanism of their formation is open to speculation. We report two patients with a follicular skin eruption (Pityrosporum folliculitis) where pseudoactinomycotic granules were found in the skin biopsies. To the best of our knowledge, such findings have not previously been reported, but supposedly they are not rare. In order to avoid an incorrect diagnosis of actinomycosis, and unnecessary therapy, it is important to be familiar with the phenomenon. PMID- 1939790 TI - Medusa head-like granules in squamous cell carcinoma with differentiation toward a hair follicle structure. AB - A case of squamous cell carcinoma (SCC) with regional lymph node metastasis in a 69-year-old Japanese man is reported. The tumor was characterized by the proliferation of peripheral basaloid, inner squamoid, and glycogen-rich cells, the presence of trichilemmal keratinization, and the presence of ladder-like, membrane-coating granules. These findings suggested that this tumor differentiates toward a hair-follicle structure. The most interesting feature of this tumor was the presence of medusa head-like granules in the cytoplasm of the clear squamoid cells adjacent to the keratinized cells. We have been unable to find any other studies of these granules in squamous cell carcinoma. PMID- 1939791 TI - A clinical study on direct and indirect Class II posterior composite resin restorations: design of the investigation. AB - The combination of composite resins with adhesive intermediate agents and techniques is still questionable with respect to application to posterior regions of the dentition. To add data to the information already available about the clinical behavior and longevity of class II composite resin restorations, a longitudinal study has been started; its design is discussed in this paper. PMID- 1939792 TI - The treatment of erosion using porcelain veneers. AB - Two cases reported here demonstrate the use of porcelain veneers to restore lost tooth tissue due to erosion. The veneers have advantages compared with other restorations in terms of aesthetics and resistance to wear. The patients described in these two reports have been seen over periods of two and three years and have been satisfied with the results, with each reporting no further pain. PMID- 1939793 TI - The CO2 laser in surgery of vascular tumors of the oral cavity in children. AB - The three cases of children treated for excision of oral hemangiomas presented here illustrate the advantages of using the CO2 laser rather than a scalpel in surgery for vascular lesions of the oral cavity. This laser has the ability to coagulate, vaporize, or cut; its main advantage, however, is its ability to seal blood vessels during surgery. Satisfactory healing in infants and children makes the CO2 laser the preferred method for performing vascular surgery. PMID- 1939794 TI - A study of children's taste and visual preferences in dentifrices. AB - Variables and gimmicks can make choosing a dentifrice for a child complicated. Various flavors, colors, shapes, consistency, labelling, and type of dispensers provide a constellation of choices for the consumer. This study sought to determine whether children actually prefer the dentifrices designed for them. Visually the child-oriented products were preferred; modern containers were preferred over the traditional. In terms of taste, however, "child-flavored" dentifrices were not preferred over the regular flavor of the same brand, when one is tasted after the other. PMID- 1939795 TI - Child patient behavior: a new perspective. AB - All behavior depends on responses of the nervous system (Shepherd 1988). Alkon demonstrated physical changes in the nervous systems of Hermissenda crassicornis and rabbits at the molecular level following behavioral conditioning. This physical change resulted in a reduced flow of potassium ions across the neuronal cell membrane for some time, with resultant enhanced excitability during this period. It is suggested that behavioral deterioration in children during sequential dental visits might be the result of a reduced potassium ion flow across the neuronal cell membrane, with resultant enhanced excitability during this period. Alkon also reported that in a "conditioned" stimulus, information flows along a "collateral pathway" formed in the course of the learning experience. It is hypothesized that behavioral improvement in children following positive dental experiences (model learning and desensitization) may be due to the information of the "conditioned" dental stimulus flowing along a "collateral pathway" formed in the course of the learning experience. PMID- 1939796 TI - Management of a departmental budget using an electronic spreadsheet. AB - Many dental school departments utilize computers, which provide the chairperson with important information on the status of the departmental budget. With the appropriate software, awareness of the funds remaining in each of the budget categories allows rapid decisions on a variety of issues. A computer-driven spreadsheet can be indispensable, providing essential information on current income and disbursements, and facilitating comparison with previous, current, and projected operations. PMID- 1939797 TI - A model for a children's dental health carnival. AB - A children's dental health carnival can yield many benefits. Some of these are: The general public becomes better informed regarding the importance of dentistry for children; children are presented with preventive-dentistry information in an entertaining environment; and students gain experience in organizing and participating in a community service project. The Children's Dental Health Carnivals have provided the children of Lincoln, Nebraska and the University of Nebraska Medical Center College of Dentistry with these benefits. The authors would be pleased to share additional information with interested parties. PMID- 1939798 TI - Impeded eruption of a permanent maxillary incisor by a denticle and a cyst. AB - Cysts and tumors, including odontomas, can delay the eruption of teeth. In this case the delay was due to a denticle and a cyst. PMID- 1939799 TI - Ingestion of dental mirror fragments: report of case. AB - A case is reported in which one treated pediatric patient gave his plastic, disposable dental mirror to a 2.5-year-old sibling, who while playing chewed on the mirror and the mirrored glass surface broke in the child's mouth. After thorough examination including x-rays, the patient was released with no further complications. Potentially severe injuries could have occurred, resulting in legal liabilities. PMID- 1939800 TI - The strained relationship between rights and responsibilities: an enigma. PMID- 1939802 TI - AIDS and HIV infections in children. PMID- 1939801 TI - Evaluation of treatment times for Class II composite resin restorations. AB - This article describes the results of an investigation into the treatment time required for the placement of Class II composite resin restorations. For purposes of this study, three dentists made 183 standard Class II composite resin restorations, both two-surface and three-surface, according to a detailed treatment protocol. Time registrations were carried out during the treatments, and each treatment was divided into five sections, each representing one stage in the restorative process. Of the various factors which may affect treatment time, the following were studied: the dentist; the type of tooth; the type of restoration; and the presence of an existing amalgam restoration in the tooth to be restored. Following in transformation of the treatment times obtained, an analysis of variance was employed. In this study the average treatment time for Class II composite resin restoration was 41.8 minutes. The results indicated that the factors mentioned above significantly affect the treatment time. In addition, the treatment time of one of the dentists was influenced by a marked learning effect. PMID- 1939803 TI - The prevalence of postoperative sensitivity in teeth restored with Class II composite resin restorations. AB - Postoperative sensitivity is one of the problems a dentist can encounter after restoration of a tooth with composite resin. To reduce the possible causes of these complaints, the operative procedure has been adapted to some suggestions of other investigators. In this study the postoperative sensitivity was evaluated in a comparison between composite resin and amalgam: 244 (standard) class II restorations were made by three dentists in fifty-six patients. Each patient received one or two series of four experimental restorations: three of composite resin (Herculite XR, Clearfil Ray Posterior, Visiomolar) and one of amalgam (Tytin). All restorations were made according to a fixed protocol. The occurrence of postoperative sensitivity was recorded. Fifty-seven restorations showed a varying period of postoperative sensitivity; no case lasted longer than half a year. Molars have more postoperative sensitivity than premolars; the difference, however, is not significant (P greater than 0.05). The study shows further that there is no difference in postoperative sensitivity between restorations of composite resin and those of amalgam. The occurrence of postoperative sensitivity does not seem to be influenced by the choice of treatment procedure, type of tooth (premolar/molar), or by the patient or the dentist. PMID- 1939805 TI - Generalized juvenile periodontitis in a thirteen-year-old child. AB - There have been two previous cases reported in which children with a possible history of Prepubertal Periodontitis (PP) developed Generalized Juvenile Periodontitis (GJP) in their permanent dentitions at circumpubescent ages. This paper reports a case in which an apparently healthy 13-year-old girl, whose radiographs at 6 1/2 years of age showed horizontal bone loss around the primary molars, developed GJP. Blood tests (CBC, WBC differential, fasting glucose level, serum alkaline phosphatase) and a gingival biopsy were performed to exclude possible systemic diseases that might have been associated with alveolar bone resorption. Neutrophil (PMN) chemotaxis (CX) and adhesion molecule CD11b levels were also examined. The results of these tests were all within the normal range. This case report illustrates that an apparently healthy patient with PP may develop advanced periodontitis at a circumpubescent age. PMID- 1939804 TI - Management of oral complications associated with cancer therapy in pediatric patients. AB - Treatment for childhood malignancies has improved markedly in recent years. However, radiation and chemotherapy are often associated with morbidity involving oral tissues. Complications include mucositis, infection, xerostomia, and gingival bleeding. Children often acquire additional long-term sequelae due to potential impairment of growth and development. Management of oral complications has routinely consisted of multi-agent topical mouthrinses; oral and intravenous agents are also prescribed depending on the nature and severity of complications. The efficacy of multi-agent topical regimens is difficult to assess and long-term studies supporting such treatment are not available. Consequently, use of multiagent mouthrinses is declining in favor of 0.12 percent chlorhexidine rinse. In children, appropriate management and prevention of oral complications are essential and require that dental care be integrated with cancer treatment. PMID- 1939807 TI - Increasing numbers of pediatric AIDS patients. AB - Few--if any--dental practitioners are unaware of the increasing changes occurring in dental and medical practices as a result of this deadly disease. PMID- 1939806 TI - Radiographic features of the bones of the hand and wrist in achondroplasia: report of case. AB - Achondroplasia is a well-established and documented medical condition. Most of the diagnostic features are discernible from a clinical examination, which are complemented by radiographic findings of the bones of the skeleton. The findings from the hand-and-wrist radiograph of an affected Southern Chinese male infant, age thirty-nine-months, are reported. The findings from this case indicated an infrequently reported abnormality in the development of the hand in achondroplasia. PMID- 1939808 TI - Water purification systems and recommendations for fluoride supplementation. AB - In communities that do not fluoridate water supplies, or homes that have fluoride removed from their water, fluoride supplementation may be necessary. The AAPD guide is reviewed, with dosage recommendations provided. Water purifications are described and reviewed. Dentists should ask their patients about their drinking water. PMID- 1939810 TI - Single maxillary central incisors in the midline. AB - A single maxillary central incisor in both the primary and the permanent dentition is a rare phenomenon. Attempts to explain the etiology of this condition included "fusion across the midline", "conation" and "double tooth". Three cases are presented with morphologically normal single incisors in the permanent dentition, and evidence of single central incisors in the primary dentition. Agenesis seems to be the preferred etiologic explanation. PMID- 1939811 TI - HIV infection and AIDS in children increase. PMID- 1939809 TI - Premature extractions of primary molars and the crown/root ratio of their permanent successors. AB - The effect of premature extractions of primary molars on further development of their successors was studied. A group of forty-six children with fifty-three unilaterally extracted mandibular primary molars was examined when the successors completed their root development. Radiographs of the successors to the extracted molars and their antimeres, which served as internal controls, were taken using the long-cone technique. Crown and root length and area in cross-section, were measured from tracings of the studied teeth and crown/root ratios were calculated. Significantly (p less than 0.05) larger area ratio in the extraction group was found suggesting a smaller root area. In addition, root foreshortening for the first premolars and diminished root area for the second premolars, both successors to teeth extracted after the age of eight years, were found. Although statistically significant, all of the differences were of no clinical importance. PMID- 1939812 TI - Responsibilities of the health professional. PMID- 1939813 TI - Response of the oral mucosa to denture wearing. AB - This paper reviews both past and current knowledge concerning the controversial subject of mucosal responses associated with denture wearing. The subject has been considered in terms of both gross clinical and histopathological changes arising from daily prosthesis use. Displacement of basal seat tissues during function has been discussed, along with denture-induced alterations of the local microfloral ecosystems. The influences of common drugs and therapeutic regimens such as ionizing radiation treatments have been considered, and as with all the fields discussed, have been related to clinical use and success of prostheses. PMID- 1939814 TI - Dentine hypersensitivity--effects of some proprietary mouthwashes on the dentine smear layer: a SEM study. AB - Exposed dentine may be sensitive to stimuli depending on the patency of the dentinal tubules. Most abrasive elements tend to produce a smear layer which obturates the dentinal tubules. This layer is easily removed by a number of erosive agents, particularly dietary acids. Mouthwashes are increasingly used and largely investigated for possible benefits to dental health. Rarely do studies assess potential detrimental activity. The aim of the present study was to examine effects of mouthwashes on dentine. Smear layers artificially produced on dentine sections were exposed, for time periods ranging from 3 to 300 min, to mouthrinses alone, or with subsequent brushing for 2 min using water or a fluoride toothpaste. Assessments were made by scanning electron microscopy. Of the nine rinses tested, six produced no consistently observable changes compared to water treated controls at any time period with or without brushing. A hexetidine rinse and a fluoride/antiseptic rinse both exposed tubules after exposure times of 2 h and longer, an effect enhanced by post-treatment brushing. A phenolic antiseptic rinse consistently removed the smear layer from specimens, an effect enhanced by brushing such that after 10 min exposure and 2 min brushing many tubules were open at the surface. The results indicate that the use of some mouthrinses could predispose to excessive tooth substance loss and dentine hypersensitivity, particularly if used prior to toothbrushing. There is a need to determine whether the intermittent use of some mouthrinses produces cumulative effects on dentine. PMID- 1939815 TI - Five-year findings of a multiclinical trial for a posterior composite. AB - This paper reports the 5-year findings of a multiclinical (n = 11) trial of a posterior composite restorative. The overall findings, based on data collected from 649 (68 per cent) of the 958 restorations originally included in the study, indicate that the material evaluated satisfies established clinical requirements for posterior composites over periods of up to 5 years. Deviations in the reporting of certain elements of the data appear to have been related to local variations in method. PMID- 1939816 TI - A preliminary investigation into the longevity and causes of failure of single unit extracoronal restorations. AB - Four types of single unit restoration, including porcelain jacket, full and partial veneer, and metal ceramic crowns provided at the Prince Philip Dental Hospital in Hong Kong were investigated for evidence of failure. Of the 4658 units of restoration provided between 1981 and 1989, 100 restorations of each type were selected at random by computer. The relevant patient were identified and invited to return for a review appointment. A total of 132 patients attended and 152 crowns were examined. The average length of service was 34 months at the date of examination. Using strict criteria, 21 (14 per cent) restorations were deemed to have failed. Technical failure was the most prevalent cause of failure, followed by aesthetic complaints and endodontic problems. The failure rates ranged from 2.4 to 7.8 per cent per year for the different crowns in order of: partial veneer less than full veneer less than metal ceramic less than porcelain jacket crowns. Fracture of restoration, which affected metal ceramic and porcelain jacket crowns, was the single most frequent cause of failure observed in this study. PMID- 1939817 TI - Clinical, radiographic and histological characteristics of secondary retention of permanent molars. AB - Secondary retention refers to the cessation of eruption of a tooth after emergence neither due to a physical barrier in the path of eruption nor as a result of an abnormal position. In this study, the clinical and radiographic features of 81 secondary retained permanent molars in a group of 53 patients were evaluated. Retained molars removed for therapeutic reasons (n = 38) were examined histologically to detect any areas of ankylosis. The first molars in the mandible and maxilla were most frequently affected. The mean infraocclusion at the patients' first visit was 4.3 +/- 1.9 mm. After 6 months, infraocclusion increased in adolescents but was stable in adults. Tilting of the adjacent teeth was observed in 39 cases. A sharp, solid percussion sound and a partial absence of the periodontal ligament space on radiographs were noted in less than one fifth of the affected molars, while histological evaluation revealed that local areas of ankylosis were present in all cases. From the data relating to the 38 molars removed for therapeutic reasons, the sensitivity of the percussion test and radiographic evaluation was found to be 29 and 21 per cent respectively. During a period of 4 years, six new cases of secondary retention were observed in the same population. From this study it is concluded that secondary retention of permanent molars seems to be associated with focal ankylosis and that percussion tests and radiographs are not sufficiently reliable to exclude the presence of ankylotic areas. The presence of ankylotic areas and tendency of infraocclusion to increase in adolescents but to be stable in adults have major implications for therapy. PMID- 1939818 TI - Tin oxide coating of aluminous porcelain by reactive ion plating. AB - Alumina reinforced dental porcelain has been coated directly with tin oxide by reactive ion plating. Samples were prepared at different distances from the tin source in the ion plating rig. Tensile bond strengths of treated and untreated porcelain discs to a commercially available phosphate-methacrylate based dental cement were determined. Bond strengths of certain coated samples were found to be in excess of the cohesive strength of the porcelain substrates (greater than 7.8 MPa), whereas untreated porcelain achieved an average bond strength of only 3.4 MPa. The microstructures of coatings produced under conditions similar to those which yielded the maximum bond strength were examined in a scanning electron microscope and were found to be approximately 0.5 microns thick. It is believed that ion plating has great potential for rendering inert ceramic surfaces capable of direct bonding to dental cements. PMID- 1939819 TI - Acrylic denture distortion following double processing with microwaves or heat. AB - The present study compared the fit of acrylic resin bases subjected to two curing cycles in a water-bath or in a microwave oven. Resin bases were processed on duplicate stone casts prepared from a cobalt chromium master die. Ten bases, composed of conventional polymethylmethacrylate, were cured in a water-bath for 7 h at 70 degrees C and 3 h at 100 degrees C, and a further 10 cured in a domestic microwave oven at 65 W for 25 min. Ten bases composed of polymethylmethacrylate modified by means of a chemical activator were cured at 100 degrees C in a water bath for 20 min. All bases were then subjected to a second curing cycle following addition of new acrylic resin to the alveolar ridge areas. Following each curing cycle the fit of the posterior border of each base was evaluated. A silicone impression material was used to form indices between the bases and the master die, these were then invested in stone and sectioned to allow cross-sectional measurement by means of an eyepiece micrometer. A one-way analysis of variance and unpaired Student's t tests were employed to compare the differences in distortion of the three groups. The differences in distortion between the first and second curing cycles were significant for all curing methods (P less than 0.001). However, microwave curing caused significantly less distortion of the denture base than short water-bath curing, especially in the centre of the palate (P less than 0.001). PMID- 1939820 TI - Accuracy of dental surveyors. AB - Maximum lateral forces as measured by strain gauges mounted on the analysing rod of a Nesor surveyor for four operators during surveying procedures ranged from 81 to 110 cN (mean 92.4 cN). Maximum lateral forces used when trimming blockout and inlay wax ranged from 159 to 184 cN (mean 169 cN) and 137 to 196 cN (mean 172 cN), respectively. Mean tilting errors produced in the vertical surveying arm by lateral loads of 98 and 196 cN (i.e. weights of 100 and 200 g) were determined to be 0.29 and 0.42 degrees for five Nesor surveyors and 0.21 and 0.36 degrees for five Krupps surveyors, respectively. All surveyors had been in constant use for at least 12 years. Play in the bearings of the horizontal arm due to loads of the same magnitude applied obliquely produced an additional mean error of approximately 0.5 degrees in the Krupps surveyors. Finally, discrepancies of up to approximately +/- 0.04 mm were found in 10 undercut gauges in each of the nominal sizes 0.25, 0.50 and 0.75 mm. It is concluded that surveyors and their accessories should be checked and serviced regularly, and possible sources of error pointed out to potential users. PMID- 1939822 TI - Application of a sucrose indicator strip to evaluate salivary sucrose clearance. AB - This study examined salivary sucrose clearance times of 96 subjects using sucrose indicator strips. Subjects with high caries experience had a longer salivary sucrose clearance time than those with a low caries experience. The flow rate of unstimulated but not of stimulated saliva was significantly related to sucrose clearance. This finding is consistent with that of other studies on salivary clearance. The sucrose indicator strips are simple to use and sucrose clearance tests using these strips do involve instrumental analyses. It is concluded that the strips investigated are simple and effective and merit further investigation. PMID- 1939821 TI - Influence of mixing disinfectant solutions into alginate on working time and accuracy. AB - Possible transfer of pathogens from dental surgery to dental laboratory is of concern to the profession. This study investigates changes in the working time and accuracy of an alginate impression material when mixed with solutions of selected disinfectants rather than water. The results indicate that certain disinfectant solutions, when used as a water substitute, do not modify the working time of the alginate investigated beyond acceptable limits and have no significant effect on the dimensional accuracy of that material. The use of a 0.2 per cent solution of chlorhexidene gluconate is recommended as a water substitute for the alginate investigated. PMID- 1939823 TI - Alfentanil with methohexitone in paediatric dental anaesthesia. AB - Children recovering from intravenous methohexitone anaesthesia given for simple dental extractions frequently cry, or are restless and confused, during emergence from anaesthesia. This is disturbing for parents and other children. In an attempt to resolve this problem various doses of alfentanil (2.5, 5.0, 7.5 and 10 micrograms/kg) were added to a standard intravenous dose of methohexitone (2 mg/kg), with the effects being assessed by comparison with a control group who received methohexitone only. The incidence of crying recorded was significantly lower in the group receiving the highest alfentanil supplement (10 micrograms/kg), when compared with the incidence in the group given lower doses of alfentanil or methohexitone alone. Among those who cried, there was a significant delay in onset in the high alfentanil dose group. No adverse effects were observed. PMID- 1939824 TI - Lack of correlation between food retention on the human dentition and consumer perception of food stickiness. AB - When dental health professionals advise that sticky foods be avoided, it is left to the consumer to choose correctly among different foods. In this study, comparisons were made among consumer ratings of stickiness of 21 commercially available foods and objective measurements of tooth retention of each of the foods. No correlation was found between the two, and neither the rates of clearance of food particles from the teeth nor the rates of clearance of food derived sugars from the saliva correlated with ratings of food stickiness. Cookies, crackers, and potato chips were most retentive, whereas caramels, jelly beans, raisins, and milk chocolate bars were among those poorly retained. Clearance rates appeared to vary inversely with initial retention. However, chocolate-caramel bars exhibited high initial retention and a very rapid rate of clearance from the teeth. The findings show that consumers cannot accurately assess the retentiveness of foods and, thus, the advise simply to avoid sticky ones is inadequate. PMID- 1939825 TI - Compensatory hyperplasia of the rat submandibular gland following unilateral extirpation. AB - This study investigated the morphological changes in rat submandibular glands undergoing compensatory hyperplasia. Fifteen adult male rats underwent left submandibulectomy, after which they were killed in groups of five (at days 3, 7, and 14), and their right submandibular glands (SMG) were excised. Fifteen control rats were killed in groups of five (at days 0, 7, and 14), and their right SMG were removed. Sections of 3 microns were cut, and the parenchymal and stromal cells were counted in 50 microscopic fields and sorted according to their morphological features and "class". Class is equivalent to the number of nuclei in an acinar or tubular cross-section. No change in glandular weight was noted post-surgery. Total cell count/field rose to 138.5 +/- 7.1% of control values on day 3 after gland extirpation, remaining almost constant thereafter until the end of the experiment. Acinar cell count and class showed a 154.1% peak on day 3, followed by a 30% drop in cell count by day 7 and an equivalent decline in class by day 14. Tubular cell count increased gradually to 146.5% by day 14, without a change in class. In the first week, the increase in tubular cells was mainly due to intercalated duct (ID) cells, while in the second week, there was a sharp rise in granular duct (GD) cells. This diverging cellular behavior indicates that the GD cell stems from the ID cell. The cellular changes in the hyperplastic SMG indicate death of newly generated acinar cells and expansion of the glandular progenitor compartment, as expressed in elongation of the ID. PMID- 1939826 TI - Scanning and contact microradiographic study of the effect of degree of saturation on the rate of enamel demineralization. AB - The effect of degree of saturation with respect to hydroxyapatite (DSHA) on enamel section demineralization was studied by contact and scanning microradiography (CMR and SMR). Two aspects were studied: (1) the effect of different values of DSHA at constant pH, and (2) the effect of constant DSHA with variable pH. In the pH range (2.5-4.5) and time scale (0-120 h) studied, the DSHA was more important in determining the rate of enamel lesion progression than was the pH. PMID- 1939827 TI - Induction of calcium phosphate precipitation by titanium dioxide. AB - Titanium powder and various titanium dioxides were tested for their capacity to reduce the induction time for calcium phosphate precipitation from supersaturated solutions. Only after a pretreatment aimed at increasing its oxide surface layer was titanium powder found to accelerate the precipitation from solutions containing 2 mmol/L CaCl2, 2 mmol/L KH2PO4, 50 mmol/L Hepes, pH 7.2, and to induce precipitation from metastable solutions containing 1.2 mmol/L CaCl2, 1.2 mmol/L KH2PO4, 50 mmol/L Hepes, pH 7.2, at 37 degrees C. Even stronger effects were found when suspensions of the titanium dioxides anatase or rutile (10-50 micrograms/mL) were added to these solutions. TiO2 appeared to serve as a reactive substrate for secondary nucleation at a wide range of calcium-to phosphate ratios and concentrations, even in the presence of 40 mg/mL bovine serum albumin, which completely inhibited precipitation in control incubations. These results suggest that the oxide surface layer of titanium implants may induce calcium phosphate precipitation in the metal-to-bone interface, which may play a role in the integration of such implants in bone. PMID- 1939828 TI - Age-hardening mechanisms in a commercial dental gold alloy containing platinum and palladium. AB - The age-hardening mechanism of a commercial dental gold alloy containing platinum and palladium (in wt.%, 15 Cu, 6 Ag, 5 Pt, 3 Pd, 3 Zn, with the balance as gold) was elucidated by means of electrical resistivity, hardness tests, x-ray and electron diffraction and electron microscopy, as well as high-resolution electron microscopy. The sequence of phase transformations during isothermal aging below the critical temperature, Tc = 825 K, was described as follows: disordered solid solution alpha 0 (FCC)----metastable AuCu I' ordered phase (FCT)----metastable alpha 2 disordered phase (FCC) equilibrium AuCu I ordered phase (FCT) + equilibrium alpha 2 disordered phase (FCC). The hardening was due to the introduction of coherency strain at the interface between the AuCu I' platelet and the matrix. These ordered platelets had mutually perpendicular c-axes to compensate for the strain introduced by their tetragonality. A loss of coherency at the interface brought about softening of the alloy, i.e., over-aging. PMID- 1939829 TI - Physical properties of stainless-steel and silver-reinforced glass-ionomer cements. AB - The purpose of this study was to compare specific physical properties of an experimental stainless-steel-reinforced glass-ionomer cement with those of two commercially available silver-reinforced cements. Properties evaluated were compressive and diametral tensile strengths (one and 24 h), percent solubility in 0.01 mol/L lactic acid over 23 h, and working and setting times. Cylindrical specimens 6 mm (diameter) x 12 mm were prepared and maintained in distilled water at 37 +/- 2 degrees C and then tested on an MTS mechanical testing machine with a cross-head displacement rate of 0.5 mm/min for the diametral tensile strength test and 1.0 mm/min for the compressive strength test. ANOVA and Tukey's Studentized Multiple Range Test indicated significant differences between the experimental and commercially available cements for both compressive and tensile strengths at one and 24 h (p less than 0.01). The experimental stainless-steel reinforced cement appeared to be significantly stronger in both tensile and compressive strengths than either of the commercially available cements. Working and setting times--as well as acid solubility of the experimental cement--also compared favorably with those of the commercial cements. Results suggest that the stainless-steel-reinforced glass-ionomer cement possesses strength properties that should lead to a stronger, more fracture-resistant restorative filling material when compared with those presently available. PMID- 1939830 TI - Kinetics of bone-resorbing activity in developing periapical lesions. AB - The presence and kinetics of bone-resorbing activity in periapical lesions were studied with a rat model system. Lesions were found to expand most rapidly between induction on day 0 and day 15 ("active phase"), with enlargement occurring at a slower rate thereafter (days 20 and 30, "chronic phase"), as assessed by measurement of magnified radiographs and automated image analysis. Pooled extracts of periapical tissues obtained on day 15 contained significant levels of bone-resorbing activity, as determined by 45Ca release from pre-labeled fetal rat long bones. Normal rat dental pulp and periodontal ligament contained no activity. In two kinetic experiments, highest levels of bone-resorbing activity were detected in tissues on days 10 (10.4% and 11.6% specific 45Ca release/mg/mL) and 15 (8.9%). Activity declined thereafter on day 20 (4.4% and 6.1%) to near baseline levels by day 30 (1.4% and 3.3%). Identical levels of resorbing activity were found in the presence or absence of polymyxin-B, an inhibitor of bacterial lipopolysaccharide. These findings demonstrate that bone resorbing activity is temporarily related to periapical bone destruction and suggest that this model may be useful for studies of mediators that are involved in the pathogenesis of inflammatory bone resorption. PMID- 1939831 TI - Characteristics of masticatory mandibular movements and velocity in growing individuals and young adults. AB - Studies of the development of mastication in the normal growing individual have received little attention in the literature. The aim of this study was to determine whether changes in oral motor function occurred during growth. Ninety healthy individuals with normal occlusion were divided into six groups of males and females, 9-10, 13-15, and 20-22 years of age. Oral motor function, with respect to mandibular displacement and velocity, was monitored with an opto electronic method. The results revealed that the total duration of the masticatory cycle was not influenced by age or gender. However, the time distribution between the different phases was found to be influenced by the age factor, causing a longer opening time and a shorter closing time in the adults. In mastication, both mandibular displacement and the mandibular velocity in closing were less in females. A reduction of the masticatory opening velocity and an increase in closing velocity were observed with increasing age. Physiological maturation of the masticatory system due to central and peripheral changes and functional adjustments due to changes in dentition and skeletal growth may be the underlying reasons for our findings. PMID- 1939832 TI - A quantitative analysis of mineral loss and shrinkage of in vitro demineralized human root surfaces. AB - Demineralization of dentin specimens proceeds at a faster rate than that of enamel. Although this is generally accepted, a quantification of the rate of formation of root lesions is hampered by the shrinkage of the lesions when these are dried prior to microradiographic analysis. This leads to a significant underestimation of the lesion depth and total mineral loss. The aim of this paper was to quantitate the rate of mineral loss during root lesion formation in vitro and to determine the shrinkage of root specimens as a result of drying. Unerupted roots of human teeth were subjected to a demineralizing system of 0.1 mol/L lactate buffer (pH = 4.8) with 0.2 mmol/L methanehydroxydiphosphonate during four, 11, 22, and 44 days. The root lesions were assessed by quantitative microradiography. The demineralizing solutions were analyzed to determine the amounts of root tissue dissolved. A comparison of these two sets of data showed that, with the demineralizing system used, root lesions may shrink up to 62%. Fixation of the specimens in fixative did not affect this shrinkage. Chemical analysis showed that mineral loss proceeded linearly with time. From the data sets of this study, a model was developed to compensate for the shrinkage in the dentin specimens. In this way, it was possible to calculate the lesion depth at four demineralization times as being 130, 220, 320, and 530 microns, respectively. These values were in agreement with a microscopic determination of the lesion depth. PMID- 1939833 TI - Enumeration of oral streptococci on media containing different concentrations of sodium and potassium ions. AB - Laboratory "type" strains of oral streptococci were screened for their ability to grow on mitis-salivarius agar (MSA) in the presence of increasing concentrations of either Na+ or K+ up to 500 mmol/L. Strains were generally better able to withstand increasing concentrations of Na+ than K+, although low numbers of colony-forming units (cfus) were seen with the highest concentration of either cation. Two strains of Streptococcus mutans, Ingbritt 162 and Ingbritt 175, behaved differently when the concentration of cation was increased from 50 to 200 mmol/L; the latter showed a marked increase in the number of cfus when the Na+ concentration was increased from 50 to 200 mmol/L, whereas there was a decrease with strain Ingbritt 162. Strains of oral streptococci from the saliva of adults and children were isolated on modified MSA containing known concentrations of Na+ and K+ and further examined if they showed "mutans-like" colony morphology. The number of cfus generally dropped as the concentration of Na+ or K+ was increased from 200 to 350 or 500 mmol/L. Greater numbers of streptococci were tolerant to Na+ than to K+. Half of the isolates were members of the Streptococcus sanguis group (SSG), either Streptococcus mitis or S. sanguis II, and these were more tolerant to high concentrations of Na+ or K+ than other isolates that were identified as Streptococcus morbillorum, Streptococcus acidominimus, and Streptococcus milleri. PMID- 1939834 TI - Effect of examining half the teeth in a partial periodontal recording of older adults. AB - Limited evidence to date has suggested that half-mouth examinations can be used in epidemiological surveys for accurate estimation of the prevalence of periodontal conditions. This study investigated the accuracy and efficiency of half-mouth periodontal examinations of mesial and buccal sites by comparing whole mouth findings from those sites with findings that would have been obtained by examining only two randomly selected quadrants of teeth in three older dentate adult populations: 263 whites in Iowa, 309 whites in North Carolina, and 384 blacks in North Carolina. Mean half-mouth scores for gingival recession, pocket depth, attachment loss, and Extent and Severity Index were almost identical to those of mean whole-mouth scores, with correlations between means exceeding 0.93. However, the proportions of the population having selected levels of moderate or severe periodontal disease in mesial and buccal sites were underestimated by as much as 13%. This study showed that half-mouth examinations can be accurate and efficient in estimating mean periodontal measures, but may underestimate the prevalence of periodontal conditions. PMID- 1939836 TI - General practice residency. PMID- 1939835 TI - The effect of crown receipt on measures of gingival status. AB - Although the association between crown margins and increased inflammation and probing depth is well-established, studies examining these effects have been largely post hoc. Change in gingival status measures due to receipt of crowns may affect longitudinal evaluations in clinical trials and epidemiological studies. This study examined the effects of receipt of crowns on the periodontal health of the Ramfjord index teeth. Gingival status descriptors included measures of plaque, gingival inflammation, calculus, probing depth, and gingival recession. Changes in periodontal status scores (1987-89) for teeth receiving crowns among 67 patients were compared with change in scores for teeth not receiving crowns. Teeth that were crowned showed small, but significant, differences. These teeth had greater decreases in calculus scores for both surfaces, increases in inflammation compared with decreases for teeth not receiving crowns, and increased facial probing depths. Change in gingival recession was markedly decreased on facial surfaces among teeth receiving crowns. The results suggest that crown status should be recorded routinely in clinical trials involving gingival status, and that teeth receiving crowns during the course of the study should be eliminated from the analyses. PMID- 1939837 TI - Can learning theory and research solve some curriculum problems? PMID- 1939838 TI - Some comments on the state of dental informatics. PMID- 1939839 TI - Attributes of growth in the U.S. dental economy, 1950-89. AB - Previous research has established dentistry as a growth sector of the U.S. economy. This study examines the economic relationship between dentistry's growth and factors operating on the demand and supply sides of the dental market. Output, defined as real per capita dental expenditures, was hypothesized to be a function of consumer income, dental insurance and the supply of dentists. Data for the period 1950-89, were analyzed using a generalized least squares approach. The analysis supported the hypothesis, indicating a significant relationship between growth in the dental sector and economic market factors. The study concludes that dentistry's real growth since 1950 was: (1) induced by increases in demand, mainly attributable to insurance and to a lesser extent consumer incomes; and (2) supported by increases in supply. The findings provide support for the insurance hypothesis, which suggests that growth in dental insurance has had a significant impact on the dental economy in recent years. PMID- 1939840 TI - Proceedings of the joint symposium of the Section on Educational Research/Development and Curriculum, and the Special Interest Group of Academic Deans: faculty development: essence of vitality. PMID- 1939841 TI - Faculty development: essence of faculty and institutional vitality. PMID- 1939842 TI - Development strategies: more than workshops. PMID- 1939843 TI - The developmental nature of faculty careers. PMID- 1939845 TI - AADS involvement in faculty development: where we have been and where we are going. PMID- 1939844 TI - Faculty development: policies and practices. PMID- 1939846 TI - Mentoring: an administrative perspective. PMID- 1939847 TI - The research consultant in dental education. PMID- 1939848 TI - Mentoring and pretenure faculty development. PMID- 1939849 TI - The future of promotion and tenure for dental school faculty--a view from the university. PMID- 1939850 TI - Enrollment trends, women, and minorities in advanced general dentistry programs. PMID- 1939851 TI - Stimulation of fibronectin secretion in cultured human keratinocytes by transforming growth factor-beta not by other growth inhibitory substances. AB - We investigated the effects of various growth inhibitory substances on fibronectin secretion in cultured normal human keratinocytes. Fibronectin secretion in keratinocytes was expressed by two methods: immunofluorescent staining of cells with anti-human fibronectin antibody, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis of [35S]-labeled proteins secreted by the cells followed by autoradiography. With immunofluorescent staining, the extracellular fibronectin was observed as coarse fibrils only in some cells of the control culture, while cells treated with 20 ng/ml transforming growth factor beta 1 (TGF-beta 1) showed intense fluorescences in a radiating pattern around most of the cells, indicating that TGF-beta 1 markedly increased fibronectin secretion in keratinocytes. Analysis of [35S]-methionine labeled proteins also revealed that TGF-beta 1 increased fibronectin secretion eight fold in culture medium. TGF-beta 2 has also induced weak increase of fibronectin secretion 1.8 fold in keratinocytes. In contrast, other growth inhibitory substances, such as tumor necrosis factor-alpha, 1,25-dihydroxyvitamin D3 and cyclosporin A, did not show any significant effects on fibronectin secretion. These results indicated that increase of fibronectin secretion is not associated with growth inhibitory effect, but rather with a specific effect of TGF-beta. PMID- 1939852 TI - Lowered Cu, Zn-superoxide dismutase activity in human malignant skin tumors. AB - We examined Cu, Zn-superoxide dismutase (SOD) activities of fifteen malignant skin tumors (four malignant melanomas, three squamous cell carcinomas, four Bowen's diseases, two basal cell epitheliomas, one sebaceous epithelioma, and one extramammary Paget's disease) and compared them with those in adjacent normal tissues of the same patients. Though there were some individual differences, all the SOD activities in tumor tissues were significantly lower than those in adjacent normal tissues of the same subjects. The average SOD activity in tumor tissues was 12.01 +/- 2.17 unit/mg protein, while that of normal tissues was 17.62 +/- 2.85. These findings agree with previous reports from various other organ tumors. PMID- 1939853 TI - Development of the hair in the rat: in vivo and in transplanted tissue. AB - Differentiation of the hair was examined in the head skin of rat embryos aged from days 12.5 to 18.5 of gestation. In 12.5-day-old embryos, the skin consisted of single layered epidermis and underlying loose connective tissue. On day 17.5 of gestation, the epidermis appeared to have a two or three layered epithelium, and the subepidermal connective tissue gave rise to an overlying dense tissue, into which blood capillaries arose from the deeper layer. The epidermis showed partial thickenings, where basal cells were arranged perpendicular to the surface of the epidermis. Beneath the epidermal thickenings, a number of connective tissue cells appeared to have accumulated and occasionally were accompanied by blood capillaries. In sequential development of the skin, the thickenings protruded as cords to the underlying dermal tissue and formed hair follicles covered with a connective tissue sheath. Skin obtained from 12.5-day-old embryos was transplanted singly or with cerebral cortex into the third ventricle of adult male rats. Thirty days after the transplantation, hairs and sebaceous glands had developed from the grafted skin. Hair growth tended to be more prominent in the cotransplanted skin grafts. However, no nerve fibers immunoreactive for substance P or calcitonin gene-related peptide (CGRP) were found in the grafted skin, although these fibers appeared in the dermis at the end of gestation in vivo. These results showed that the skin of 12.5-day-old embryos was able to induce hair growth in the third ventricle without accompanying peripheral neuronal fibers or blood capillaries, although the effects of connective tissue cells could not be ruled out. PMID- 1939854 TI - Leukemia cutis in acute myelomonocytic leukemia: infiltration to minor traumas and scars. AB - We describe a patient with acute myelomonocytic leukemia who demonstrated leukemic cell infiltration to scratched wounds and scars from trauma. A 65-year old Japanese woman developed low grade fever, headache and exanthema. Hematology testing disclosed leukocytosis of 95,600/mm3 with 65% monocytes and 9% blast cells. Infiltrated erythema and nodules were disseminated over most of her body. Moreover, linear scratched wounds and traumatic scars were indurated. Skin biopsy showed dense atypical mononuclear cell infiltration with monocytic characteristics. We discuss the possible reasons for the infiltration of leukemia cells into the wounds and scars from trauma. PMID- 1939855 TI - Diffuse neonatal hemangiomatosis with a giant cutaneous hemangioma on the axilla. AB - A case of diffuse neonatal hemangiomatosis is described. At birth, a giant tumor, 10 cm in diameter and 6 cm in height, was present on the left axilla and associated with thrombocytopenia. Numerous cherry-red papules were present on the skin and buccal mucosa. On the second day of life, the giant tumor was excised. Histological examination of the tissue revealed masses of endothelial cells embedded in fibrous tissues. Plain and enhanced computed tomography of the brain revealed a hemorrhage and two hemangiomas. The associations of intravascular papillary endothelial hyperplasia were discussed. PMID- 1939857 TI - Purpuric cutaneous manifestations in mitochondrial encephalomyopathy. AB - A six-month-old boy with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome developed repeated crops of purpuric macules on his soles and palms, which were histologically identified as hemorrhage into the dermis without inflammatory infiltrates. Transmission electron microscopy of the skin eruptions revealed various stages of endothelial degeneration in the dermal capillaries associated with consequent extravasation of erythrocytes. The degenerative change was characterized by swollen and vacuolated mitochondria which showed disintegration of their cristae. These morphological changes in the mitochondria of the endothelial cells resembled those seen in skeletal muscle fibers. Similar changes were also noted in other tissues of the skin, such as the axons of myelinated peripheral nerves and some of the keratinocytes in the epidermis. Although these fine structural features are difficult to differentiate from artifacts, abnormal mitochondria could result in functional disturbance particularly in the tissues that require relatively high kinetics, and thus contribute the symptoms of myopathy, encephalopathy, acidosis and stroke-like episodes. PMID- 1939856 TI - An unusual mechanical hyperkeratosis of the soles--health sandals keratosis. AB - A series of 13 patients with hyperkeratosis of both soles of the feet are presented. All patients developed hyperkeratosis after wearing the so-called "health sandals", which have multiple projections on their upper surfaces to stimulate the soles while walking. There was no evidence of hereditary or systemic factors producing the hyperkeratosis and it was concluded to be due to chronic mechanical stimulation of the soles. This side effect of the wearing of "health sandals" (health sandals keratosis) should be noted by dermatologists. PMID- 1939858 TI - Cutaneous porphyrias in China. AB - In China, 78 cases of cutaneous porphyrias, together with 67 cases reported by other clinicians from 1979 to 1990, were reviewed. Of a total of 145 cases, 75.2% were EPP (109 cases), but only 28 cases (19.3%) were PCT. This prevalence differs from that in other parts of the world. The article discussed this disparity and some notable points. Early diagnosis of EPP using the fluorescence microscopic test for determination of RBC protoporphyrin is important. The complication of hepatobiliary aspects in PCT and EPP was noticed. Liver disease seems to be an important precipitating factor in China. PMID- 1939859 TI - Transcutaneous PO2 and PCO2 measurements in various skin lesions. AB - Low tcPO2 levels were observed in various skin lesions, indicating that most pathological changes in the skin induce such a reduction. In contrast, the tcPCO2 changed less, with the exception of marked elevations in bullous or prenecrotic lesions. This procedure may have practical applications in clinical dermatology, particularly in quantitating the response to therapy and in predicting a necrotic change. PMID- 1939860 TI - Immunohistochemistry of cutaneous graft-versus-host disease after allogeneic bone marrow transplantation. AB - Graft-versus-host disease (GVHD) is an immunologically mediated disease occurring most frequently after allogeneic bone marrow transplantation. The aim of this study was to evaluate the contribution of immunohistochemistry in the diagnosis of cutaneous GVHD. Patients transplanted for either leukemia or beta-thalassemia were included in the study. Skin lesions of acute and chronic GVHD were examined both by direct immunofluorescence to detect immunoglobulin deposits and by an avidin-biotin-peroxidase complex technique to evaluate the inflammatory cell infiltrate. Epidermal and dermal fluorescent bodies (IgG and IgM) were frequently found in both acute and chronic GVHD. Most of the infiltrating cells were CD3+ T lymphocytes, with CD8+ cells representing the major cell population invading the epidermis both in acute GVHD and in chronic lichenoid GVHD. A small proportion of the dermal cells were CD14+ macrophages; no B cells were detected. HLA-DR, but not HLA-DQ antigens, were variably expressed by keratinocytes in all cases of acute GVHD and in chronic lichenoid GVHD. KL-1, a monoclonal antikeratin antibody specific for the 56.5 KD acidic polypeptide usually present in suprabasal keratinocytes, stained all epidermal layers, including the basal layer. Langerhans cells were dramatically reduced in number in the epidermis of both acute and chronic lichenoid GVHD. It is concluded that immunohistologic analysis may be supportive in the diagnosis of acute and early chronic lichenoid cutaneous GVHD. PMID- 1939862 TI - Clinical and immunohistochemical responses of plantar warts to topical immunotherapy with diphenylcyclopropenone. AB - A 30-year-old man with bilateral plantar warts of the mosaic type which had been resistant to standard treatment modalities was treated with diphenylcyclopropenone. After 10 weeks, the treated warts had disappeared; the untreated warts, although showing some involution, still persisted. The untreated warts, serving as a control to prove the effectiveness of topical immunotherapy, responded likewise to subsequent treatment with diphenylcyclopropenone. Wart regression was reflected histopathologically by decreases in acanthosis, papillomatosis, granular vacuolation, and hyperkeratosis. Immunohistochemically, Ki-67 expression was markedly reduced, and a reversal of the CD4/CD8 ratio was seen. These findings suggest a major role of a cell-mediated immune response in the spontaneous resolution of warts. PMID- 1939861 TI - Treatment of vitiligo with oral 5-methoxypsoralen. AB - Thirty-six patients with vitiligo were treated with oral 5-methoxypsoralen (5 MOP) and subsequently exposed to UVA irradiation. The patients were treated once or twice weekly over a period of 2-10 months, taking 40-60 mg of 5-MOP 2 hours before exposure to UVA light. The amount of exposure to UVA light was slowly increased according to the patient's tolerance. Eleven (31%) patients showed remarkable repigmentation of the areas of vitiligo within six months. Overall, 78% of the patients showed effective repigmentation. Areas of vitiligo on the face and trunk were more responsive to treatment than those on the distal part of limbs. Adverse effects due to the drug included 2 patients with nausea and 1 patient with headache. It is suggested that treatment with systemic 5-MOP is effective, safe, and useful in selected cases of vitiligo. PMID- 1939863 TI - Granulomatous tissue reaction following cosmetic eyebrow tattooing. AB - We report a case of epithelioid granuloma which occurred at the site of a previous cosmetic eyebrow tattooing. A biopsy specimen showed the organized appearance of epithelioid cell granulomas containing little pigment as well as occasional giant cells, mainly of Langhans' type, thus showing the characteristic features of granulomatous hypersensitivity. With the use of energy dispersive X ray microanalysis and inductively coupled plasma spectrometry, the presence of copper, iron, cobalt, and chromium was demonstrated. PMID- 1939864 TI - Tinea corporis due to Microsporum canis from an asymptomatic dog. AB - The patient was a 19-year-old female student who purchased a puppy from a pet shop four weeks earlier. At the time of her first examination, an annular edematous erythema with adherent scales and vesicles surrounding its margin was seen on the left forearm. On direct examination of the vesicles, fungal elements were detected, and Microsporum canis was isolated. The puppy was a Pomeranian and was kept in the house at all times. No clinical lesions were seen on the puppy, and the Wood's lamp test was negative. However, M. canis was isolated from the animal by the hairbrush method. Symptoms disappeared after the patient was treated topically with terbinafine cream for three weeks. Although the dog received no treatment whatsoever, there was no evidence of the disease on the pet. Results of the hairbrush method performed on the pet two and three weeks later were negative, but, at five weeks, it was again positive. Human infection with M. canis from an asymptomatic dog was demonstrated in this case. Attention should be paid to preventing infections from animals without lesions. PMID- 1939865 TI - Inhibition spectra of solar urticaria: a case report and a review of the Japanese cases. AB - A 34-year-old Japanese female with solar urticaria is described, who had an episode of urticarial response when she was exposed to indoor fluorescent light first and sunlight later. The action spectrum was found to range from 480 to 520 nm with an inhibition spectrum above 650 nm in the visible light by both postirradiation and preirradiation. Injection of in vitro-irradiated serum did not produce an urticarial wheal on the patient. In the Japanese literature, 17 cases of solar urticaria with inhibition spectra have been reported. The wavelength of the inhibition spectrum was longer than that of the action spectrum in each case. PMID- 1939866 TI - Interplay of intrapulmonary and extrapulmonary factors on pulmonary gas exchange during weaning. PMID- 1939867 TI - Percutaneous tracheotomy--novel technique or technical novelty? PMID- 1939869 TI - A prospective comparison of a percutaneous tracheostomy technique with standard surgical tracheostomy. AB - A prospective non-randomized study was undertaken to compare, in intensive care patients, the safety and utility of a percutaneous tracheostomy technique performed at the bedside with a surgical tracheostomy technique performed in the operating room. During a 21 month period, 153 percutaneous tracheostomies were performed. Complications occurred in 6 patients (3.9%). Secondary wound haemorrhage occurred in 4 patients and primary wound haemorrhage occurred in 2 patients. During the same period, 74 surgical tracheostomies were performed. Complications occurred in 14 patients (18.9%) which included tracheal obstruction, haemorrhage, pneumothorax, wound infection, wound breakdown and one death. In comparison to surgical tracheostomies, percutaneous tracheostomies were rapidly and easily performed at the bedside and were associated with significantly fewer complications. PMID- 1939868 TI - The pulmonary circulation in acute lung injury: a review of some recent advances. AB - 1. According to the Starling resistor model of the pulmonary circulation, the pulmonary hypertension of oleic acid lung injury, an experimental model close to the early stage of clinical ARDS, primarily results from an increased vascular closing pressure which exceeds Pla and becomes the effective outflow pressure of the pulmonary circulation. Therefore, calculated pulmonary vascular resistance should be interpreted cautiously during haemodynamic investigations in patients with ARDS. 2. Part of this increased vascular closing pressure is functional. During acute lung injury pulmonary vasomotor tone can be reduced by vasodilators, or increased by cyclooxygenase inhibitors and almitrine. 3. Pulmonary vasodilation due to infused vasodilators usually impairs gas exchange in ARDS. 4. There is evidence that HPV is altered during ARDS. Drugs capable of enhancing the efficacy of HPV could improve gas exchange. If proven safe in the future, cyclooxygenase inhibitors and almitrine are interesting compounds to be tested in ARDS. PMID- 1939870 TI - Current practice regarding invasive monitoring in intensive care units in Finland. A nationwide study of the uses of arterial, pulmonary artery and central venous catheters and their effect on outcome. The Finnish Intensive Care Study Group. AB - As part of a nationwide evaluation of intensive care, we examined patient- and hospital-related factors which could influence the patterns of utilization of arterial cannulae and central venous and pulmonary artery catheters. We also studied the possible impact of these interventions on the short-term outcome among 14,951 consecutive ICU admissions to 25 intensive care units (75% of all ICU beds) in Finland. There was considerable variation between individual units in the use of these devices even if the differences in severity of illness were taken into account. Arterial cannulation was used in 71.2%, PA catheterization in 10.6% and CVP monitoring in 49.3% of cases in teaching ICUs, excluding cardiac surgery, and in 38.5%, 2.6% and 33.1% of cases in non-teaching ICUs respectively. The factors predicting the use of invasive monitoring included extensive surgery causing a risk of cardiovascular instability, needs for mechanical ventilation, infusion of vasoactive drugs and complicated fluid therapy. Cardiovascular problems among non-operative patients increased the odds for PA catheterization but reduced them for arterial and CV cannulation. No clear-cut benefit could be found in the form of hospital mortality reduction from invasive haemodynamic monitoring, used as described in this study. PMID- 1939871 TI - Factors influencing transcutaneous oxygen and carbon dioxide measurements in adult intensive care patients. AB - Transcutaneous PO2 (PtcO2) is suggested to reflect tissue oxygenation in intensive care patients, whereas transcutaneous PCO2 (PtcCO2) is advocated as a noninvasive method for assessing PaCO2. In 24 critically ill adult patients (mean Apache II score 14.2, SD 4.7) we investigated the impact of variables that are commonly thought to determine PtcO2 and PtcCO2 measurements. A linear correlation was found between PtcO2 and PaO2 (r = 0.6; p less than or equal to 0.0001) and between PtcO2 and mean arterial blood pressure (MAP; r = 0.42; p less than or equal to 0.003). Cardiac index (CI) correlated with tc-index (PtcO2/PaO2; r = 0.31; p less than or equal to 0.03). There was no relationship between PtcO2 and hemoglobin concentration (Hb) and the position of the oxygen dissociation curve (ODC). Stepwise multiple regression analysis demonstrated a significant influence of PaO2 and MAP on PtcO2. The contribution of CI, Hb and the ODC was not significant. Only 40% of the variability of a single PtcO2 measurement could be explained by PaO2 and MAP. A significant linear correlation was demonstrated between PtcCO2 and PaCO2 (r = 0.76; p less than or equal to 0.0001) but not between PtcCO2 and CI, MAP and arterial base excess (BEa). Stepwise multiple regression analysis revealed an influence of PaCO2 and of CI on PtcCO2; 66% of the variability of a single PtcCO2-value could be explained by PaCO2 and CI. Our data demonstrate that transcutaneous derived gas tensions result from complex interaction between hemodynamic, respiratory and local factors, which can hardly be defined in ICU-patients. PMID- 1939872 TI - Procedure-related rate of contact of intensive care unit personnel with patient body fluids. AB - We prospectively recorded the frequency with which ICU personnel came in contact with body fluids in order to provide an empirical basis for the recommendation of relevant protective precautions. ICU personnel completed a questionnaire when performing a range of 29 standardized procedures. The rate of contact with body fluid was: manual ventilation (55%); catheterization of peripheral vein (36%); insertion of central venous catheter (69%); arterial puncture (18%); tracheal intubation (76%); tracheal extubation (87%); suction from mouth, pharynx or trachea (82%); drawing of blood sample (52%); establishing or discontinuing blood transfusion (50%); establishing or discontinuing infusion (20%); changing of wound dressing (52%). We suggest that the contact rates observed should be used in combination with a universal precautions policy, in order to identify procedures that are likely to involve contact with body fluid. By using gloves 95% of contacts to body fluid would have been prevented. PMID- 1939873 TI - Endoscopic injection of adrenaline for severe peptic ulcer haemorrhage in high surgical risk patients. AB - Endoscopic adrenaline-hypertonic injection was attempted in 40 patients admitted for oesophagogastroduodenal ulcer haemorrhage unresponsive to conventional medical treatment and presenting with severe underlying disease or advanced age (less than 80 years). The results were compared with our own historical controls (43 patients) treated by conventional therapy, meeting the same inclusion criteria. Permanent haemostasis was achieved in 32 patients in the injection group and 30 in the control group (NS) but emergency surgery was less frequent in the injection group (2 vs 25, p less than 0.001). Blood transfusion requirements were less in the injection group (8.5 +/- 6.2 vs 10.2 +/- 5.4, p less than 0.05) but length of hospital stay was not really different (15.7 days +/- 9.3 vs 20.9 +/- 14.4). Unfortunately, mortality was not reduced in the injection group (14/40 vs 17/43). Two lethal complications attributable to injection treatment occurred. This treatment could represent an alternative to conventional haemostatic treatment in high surgical risk patients with severe clinical bleeding, avoiding emergency surgery. In spite of the fact that we selected high-risk patients, endoscopic treatment was not able to lower the mortality (about 37%). Due to severe unpredictable side effects and potential risks of long-term massive rebleeding, this treatment should be performed electively in patients with severe clinical bleeding, as first line treatment when surgical risk factors exist or immediately before surgery in low risk patients. PMID- 1939874 TI - Measuring quality of life with the sickness impact profile: a pilot study. AB - A pilot-study was done to investigate the applicability of the sickness impact profile (SIP) in ex-ICU patients. For this study 221 consecutively admitted patients were reviewed retrospectively after excluding children, deceased patients and readmissions. SIP was assessed in these patients by either interview or questionnaire. These were divided into three groups: i) Patients interviewed at home (n = 26). ii) Patients receiving the SIP-questionnaire by mail (n = 93). iii) As for group ii, but after receiving a telephone invitation to participate (n = 102). Highest mean SIP-score was found in group i (16.3). Groups ii and iii scored 10.2 and 7.9 respectively. Analysis of variance demonstrated overall SIP scores of these groups to be significantly different. The response in group iii (77%) was significantly higher compared to group ii (56%). Data collection in Group i appeared to be most expensive costing $13.20 per patient, followed by group iii ($3.79) and group ii ($2.56). It is concluded that the self administered SIP is suitable for measuring outcome in ICU-patients and is much cheaper than the direct interview technique. The 3 different approaches should be considered as independent methods of which individual results cannot be compared. The response can be improved significantly by calling the patients before sending the questionnaire. PMID- 1939875 TI - Acute carbon monoxide intoxication and hyperbaric oxygen in pregnancy. AB - Modalities of oxygen therapy for pregnant women intoxicated with carbon monoxide (CO) are ill defined. Hyperbaric oxygen (HBO) is presumed to be hazardous to the pregnancy. On the other hand CO entails anoxic injuries in the mother and fetus. We have entered 44 pregnant women who sustained an acute carbon monoxide poisoning at home, into a prospective study in order to assess HBO tolerance. They were treated within 5.3 +/- 3.7 h (range: 1-12) of the intoxication with a combination of 2 h of HBO at a pressure of 2 atmospheres absolute (ATA) and 4 h of normobaric oxygen, irrespective of the clinical severity of the intoxication and of the age of pregnancy. Six patients were lost to obstetric follow-up. Only 2 patients sustained a spontaneous abortion: 1 within 12 h and 1 within 15 days of the intoxication. Thirty-four women gave birth to normal newborns. Finally 1 elected to undergo abortion for reasons unrelated to the intoxication and 1 gave birth to a baby with Down's syndrome. There is no evidence that HBO was involved with either abortion of our study. We conclude that HBO may be carried out in pregnant women acutely intoxicated with carbon monoxide. PMID- 1939877 TI - Percutaneous balloon pericardiostomy for non-surgical management of recurrent pericardial tamponade: a case report. AB - We report the case of a 26-year-old male with recurrent hemorrhagic cardiac tamponade occurring after initial management by needle pericardiocentesis and pigtail catheter drainage. As an alternative to open surgical pericardial fenestration, a percutaneous balloon pericardiostomy was performed with an 18 mm balloon catheter and over-the-wire insertion of a 16 F chest tube for 72 h of pericardial drainage. This non-surgical approach resulted in successful resolution of recurrent cardiac tamponade. PMID- 1939876 TI - The consequences of continuous haemofiltration on lung mechanics and extravascular lung water in a porcine endotoxic shock model. AB - Endotoxinaemia (E. coli endotoxin, 0.111.B4) and pulmonary hypertension were evoked in 20 swine, randomly assigned to receive either zero-balanced venovenous haemofiltration (HF) with an ultrafiltration and replacement rate of 600 ml/h (HF group, n = 10) or to undergo an uninfluenced spontaneous course (E group, n = 10) during a constant infusion of endotoxin until the end of the experiment. Endotoxin-induced pulmonary dysfunction was assessed on the basis of extravascular lung water (EVLW) using a thermo-dye technique via a fiberoptic intra-aortic probe, gas exchange and lung mechanics, the latter derived by a pressure-volume loop (P/V loop) of the respiratory system (super syringe, flow 30 ml/s, tidal volume 600 ml). A comparable increase in alveolo-arterial oxygen difference and a constant EVLW was observed in both groups. The progressive deterioration of hysteresis area and compliance parameters by endotoxinaemia was significantly blunted by HF. Independent of an impact on pulmonary oedema zero balanced HF modifies endotoxin induced lung injury, probably by the convective transport of mediator substances. PMID- 1939878 TI - Oesophageal obstruction during nasogastric feeding. AB - Although complications of enteral feeding are usually minor, we report an unusual and serious case of oesophageal obstruction after feeding with osmolite, a commonly used polymeric enteral feeding preparation. The patient described underwent rigid oesophagoscopy to remove the feed which had solidified and blocked the entire oesophageal lumen. The procedure resulted in oesophageal perforation which needed surgical repair by thoracolaparotomy and was followed by a difficult postoperative course. In vitro tests showed that all commonly used feeds containing casein (osmolite, ensure, ensure plus, paediasure, fortison, and pulmocare) solidified at a pH of less than 5. Clinifeed (containing dried skim milk) and peptamen (containing peptides) remained liquid at a pH of less than 1. Solidified feed could be liquefied by the addition of pepsin or pancrex V (a pancreatic enzyme formulation). We conclude that solidification could occur in all feeds containing casein and that alternative feeds should be considered in patients with increased gastric acidity. In addition, pepsin or pancrex V could be used to liquefy solidified feed. PMID- 1939879 TI - Vincristine-induced recurrent laryngeal nerve paralysis in children. AB - Stridor developed in 2 children during vincristine therapy for malignancies. Indirect laryngoscopy revealed left vocal cord paralyses in both patients. One child had generalized neurotoxicity from vincristine including hypotonia, decreased gastrointestinal motility, and painful paresthesias while laryngeal nerve paralysis was the only neurotoxic manifestation in the other patient. Stridor resolved in both patients after discontinuing or decreasing the dose of vincristine. Visualization of the airway not only confirms the diagnosis, but also rules out treatable causes of stridor in the febrile, immunocompromised patient. PMID- 1939880 TI - Complete airway obstruction following near-drowning in chlorinated water. PMID- 1939881 TI - Ajmaline in non-responders to lidocaine with malignant ventricular arrhythmia after thrombolytic therapy in acute myocardial infarction. PMID- 1939882 TI - Stress-generated electric potential in renal stones due to ultrasound [43.35.Cg, 43.80.Cs, 62.20.Dc]. AB - The presence of renal calculi in the kidney causes discomfort and pain to the patients and so removal of such stones is thus important. These days, nonsurgical and noninvasive techniques are used for this purpose. In this laboratory, an ultrasonic kidney stone disintegrator is being developed. In order to know design parameters for such instrument, various physical and mechanical properties of renal calculi, have been studied. During the course of ultrasonic studies in kidney stones, "stress-generated electric potential" has been observed. The in vitro samples of the kidney stones were obtained from local hospitals in Delhi. The stones were sliced into a regular shape of 1 x 1 cm. An ultrasonic field at 2.5 and 5.5 MHz was applied to the samples normal incidence to one surface. On the two surfaces parallel to the ultrasonic beam, two electrodes were applied and an electric potential was measured across these electrodes. This stress-generated potential was measured with the help of an electrometer, and varied from 0.50 to 3.0 mV and 3.10 to 12.50 mV at the two frequencies, respectively. This investigation shows that the renal calculi exhibit a stress-generated electric voltage due to their piezoelectric property. PMID- 1939883 TI - Speech-perception aids for hearing-impaired people: current status and needed research. Working Group on Communication Aids for the Hearing-Impaired. AB - Both the overall aging of the population and its exposure to higher noise levels have increased the tendency to hearing loss and the importance of improved hearing aids for speech perception. This article reviews improvements in conventional electroacoustic hearing aids, as well as recently developed alternative classes of speech-perception aids, including surgically implanted cochlear stimulators, and vibrotactile, electrocutaneous and optical stimulating devices. It is concluded that the most effective aid for the vast majority of hearing-impaired persons is, and will remain for the immediate future, the electroacoustic hearing aid. In those cases for which no benefit is demonstrated for the electroacoustic aid, generally meaning persons with profound hearing loss, either the cochlear implant or a tactile aid may provide some improvement in the understanding of speech. In rare cases, some speech understanding in the absence of lip reading is achieved by patients with cochlear implants, for unexplained reasons. This and other pressing questions about speech processing need to be addressed by the research community if more effective aids are to be developed for the use of the 36.5 million hearing-impaired persons expected in the U.S. by the year 2050. PMID- 1939884 TI - A composite model of the auditory periphery for the processing of speech based on the filter response functions of single auditory-nerve fibers. AB - A composite model of the auditory periphery, based upon a unique analysis technique for deriving filter response characteristics from cat auditory-nerve fibers, is presented. The model is distinctive in its ability to capture a significant broadening of auditory-nerve fiber frequency selectivity as a function of increasing sound-pressure level within a computationally tractable time-invariant structure. The output of the model shows the tonotopic distribution of synchrony activity of single fibers in response to the steady state vowel [e] presented over a 40-dB range of sound-pressure levels and is compared with the population-response data of Young and Sachs (1979). The model, while limited by its time invariance, accurately captures most of the place synchrony response patterns reported by the Johns Hopkins group. In both the physiology and in the model, auditory-nerve fibers spanning a broad tonotopic range synchronize to the first formant (F1), with the proportion of units phase locked to F1 increasing appreciably at moderate to high sound-pressure levels. A smaller proportion of fibers maintain phase locking to the second and third formants across the same intensity range. At sound-pressure levels of 60 dB and above, the vast majority of fibers with characteristic frequencies greater than 3 kHz synchronize to F1 (512 Hz), rather than to frequencies in the most sensitive portion of their response range. On the basis of these response patterns it is suggested that neural synchrony is the dominant auditory-nerve representation of formant information under "normal" listening conditions in which speech signals occur across a wide range of intensities and against a background of unpredictable and frequently intense acoustic interference. PMID- 1939885 TI - Spectral cues to perception of /d, n, l/ by normal- and impaired-hearing listeners. AB - The alveolar consonants /d, n, l/ occur frequently in intervocalic position in conversational speech but have received little study for differences in their acoustic cues. Impaired- and normal-hearing listeners were investigated for use of consonant-segment versus transition-segment cues to recognition of /d, n, l/ in /aeCae/ tokens extracted from sentences. To examine the cues' contribution to /d, n, l/ recognition, the segments were degraded singly or in combinations in the tokens as follows: [aeC] or [Cae] transitions were replaced by adjacent pitch periods from the respective vowels; the consonant segments were replaced by silence or by a synthetic consonant approximating the summed low-frequency spectra of the /d, n, l/ murmurs. The results with normal-hearing listeners showed that the presence of any one of the three segments, [aeC] transition, [Cae] transition, or natural consonant segment, supported a moderate to high level of /d, n, l/ recognition, depending on the phoneme. In contrast, the severely hearing-impaired listeners' consonant recognition was poor on the basis of transition information, but better in the presence of the natural consonants. The /aeCae/'s with the synthetic consonant yielded chance level performance for the hearing-impaired listeners but good consonant recognition for the normal hearing listeners--a further indication that cues in the transitions were quite useful for the normal-hearing group but not for the hearing-impaired group. PMID- 1939887 TI - Comodulation masking release as a function of level. AB - These experiments examine the effects of masker level on the magnitude of comodulation masking release (CMR). In experiment 1, threshold was measured for detecting a 2000-Hz signal in noise bands 100 or 3200 Hz wide, centered at the signal frequency. The noise was either amplitude modulated by a low-pass-filtered noise, or was unmodulated. At noise spectrum levels of 30 and 50 dB, thresholds were lower in the 3200-Hz-wide modulated noise than in the 100-Hz-wide modulated noise or the 3200-Hz-wide unmodulated noise, indicating a CMR. The magnitude of this CMR decreased at a noise spectrum level of 10 dB, and was very small at a spectrum level of -10 dB. In experiment 2, threshold was measured for a 700-Hz signal centered in a 20-Hz wide band of noise (the on-frequency band, OFB), both in the presence and absence of eight flanking bands (FBs) whose envelopes were either identical with that of the OFB (correlated condition) or were uncorrelated. Thresholds were lower in the correlated than in the uncorrelated condition, indicating a CMR. When the OFB and the FBs were presented to the same ear, the CMR decreased when the spectrum level of all bands was below 30 dB, or when the spectrum level of the FBs was decreased below 40 dB keeping the level of the OFB constant at 40 dB. When the OFB and the FBs were presented to opposite ears, the CMR decreased when the spectrum level of all bands was decreased below 30 dB or when the spectrum level of the FBs was decreased below 40 dB, keeping the level of the OFB fixed at 40 or 60 dB. However, the CMR was almost independent of the spectrum level of the OFB (over the range 10-70 dB) when the spectrum level of the FBs was held constant at 60 dB. The results are interpreted in terms of perceptual grouping mechanisms. Implications for the measurement of CMR in hearing-impaired subjects are also discussed. PMID- 1939886 TI - Analysis of vocal tract shape and dimensions using magnetic resonance imaging: vowels. AB - Magnetic resonance imaging (MRI) techniques were used to gather basic data to apply in computational models of speech articulation. Two experiments were performed. In experiment 1, voice recordings from two male subjects were obtained simultaneously with axial, coronal, or midsagittal MR images of their vocal tracts while they produced the four point vowels. Area functions describing the individual tract shapes were obtained by measurements performed on the MR images. Digital filters derived from these functions were then used to resynthesize the vowel sounds which were compared, both perceptually and acoustically, with the subjects' original recordings. In experiment 2, axial images of the pharyngeal cavity were collected during the production of an ensemble of nine vowels. Plots of cross-sectional area versus the midsagittal width of the tract at different locations within the pharynx and for different vowel productions were used to derive a functional relationship between the two variables. Data from experiment 1 relating midsagittal width to cross-sectional area within the oral cavity were also examined. PMID- 1939888 TI - Effect of amplitude modulation on profile detection. AB - The effect of amplitude modulation on profile detection was examined in three experiments. The observer's task was to determine in which observation interval an increment was added to the 1000-Hz target component of a multitone complex in which the components were equally spaced on a logarithmic frequency scale from 200 to 5000 Hz. The target was unmodulated throughout the study. In some conditions, all nontarget components of the standard were modulated in phase; in other conditions, they were modulated with random phase. In experiment 1, the threshold was measured as a function of the modulation rate. The results show that, at low modulation rates, 5 Hz for example, modulation elevates threshold by about 13 dB. The threshold decreases as the modulation rate increases, with the threshold elevation being only 3 dB at 80 Hz. In experiment 2, threshold was measured as a function of modulation depth for both 21- and 5-component complexes. The results show that for a 5-Hz modulation rate the threshold decreases as the modulation depth decreases, and that the rate of decrease is greater for the 21-component complex than for the 5-component complex. In experiment 3, the effects of random-phase modulation were explored; the phase of the modulation waveform was randomly chosen for each component. The results show that there is no difference between in-phase and random-phase modulation when each component occupies a different critical band. If, however, two or more components occupy the same critical band, then randomizing the phase of modulation reduces the effective depth of modulation within that critical band, and the effect of modulation is thereby lessened. PMID- 1939889 TI - Effect of time compression and expansion on the discrimination of tonal patterns. AB - This experiment tested how well human listeners can discriminate between temporal patterns that are compressed or expanded in time. The listener's task was to determine whether two arrhythmic, tonal sequences had the same or different temporal patterns. According to the pattern correlation model [R. D. Sorkin, J. Acoust. Soc. Am. 87, 1695-1701 (1990)], listeners perform this task by computing the correlation between the pattern of time intervals marked by the tones in each sequence. Listener performance dropped when one of the sequences was compressed or expanded in time. In order for the model to describe the observed performance, it was necessary to postulate an internal noise component that was proportional to the magnitude of the difference between the sequence transformations. PMID- 1939890 TI - Temporal integration and multiple looks. AB - The decrease in detection and discrimination thresholds with increases in signal duration has often been taken to indicate that a process of relatively long-term temporal integration occurs in hearing. Two experiments are reported that suggest that no such process occurs. The first experiment is similar to the two-pulse experiment reported by Zwislocki [J. Zwislocki, J. Acoust. Soc. Am. 32, 1046-1059 (1960)] in which the threshold in quiet for a pair of brief pulses is measured as a function of the temporal separation between them. Our data indicate that power integration occurs only for separations less than approximately 5 ms. For separations larger than 5-10 ms, thresholds do not change with separation and the pulses appear to be processed independently. In the second experiment, brief 1 kHz tone pulses separated by 100 ms are presented during gaps in a wideband noise. The threshold for a pair of pulses is lower than that for either pulse presented alone, indicating that some type of "integration" occurs. However, the threshold for the pulse pair is not affected by changes in the level of the noise during the interval between the pulses. These data are inconsistent with the classical view of temporal integration that involves long-term integration. They are consistent with the notion that the input is sampled at a fairly high rate and that these samples or "looks" are stored in memory and can be accessed and processed selectively. This multiple-look model can account for the data from the present experiment and also can account for the data on temporal integration for tones and noise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939891 TI - Turning on a tone. AB - It is possible to choose the starting phase of a pure tone in a way that minimizes the onset noise when the tone is turned on abruptly. A spectral model shows that when the tone has a low frequency, minimum onset noise is expected for a starting phase of zero (turning on a sine tone) but when the tone has a high frequency, minimum onset noise is expected for a starting phase of +/- 90 deg (turning on a cosine tone). Listening experiments confirm the above expectations and show that the transition between low- and high-frequency domains is sharp and depends upon both the electroacoustical transducer and the individual listener. PMID- 1939892 TI - Dynamic processes in the precedence effect. AB - Three experiments were conducted to investigate the dependence of echo suppression on the auditory stimulation just prior to a test stimulus. Subjects sat in an anechoic chamber between two loudspeakers, one which presented the "lead" sound, and the other the delayed "lag" sound. In the first experiment, subjects reported whether or not they heard an echo coming from the vicinity of the lag loudspeaker during a test click pair. In seven of nine listeners, perception of the lagging sound was strongly diminished by the presence of a train of "conditioning" clicks presented just before the test click. Echo threshold increased (subjects were less sensitive to echoes) as the number of clicks in the train increased from 3 to 17. For a fixed number of clicks, the effect was essentially independent of click rate (from 1/s through 50/s) and duration of the train (from 0.5 through 8 s). A second experiment demonstrated a similar buildup of echo suppression with white noise bursts, regardless of whether the bursts in the conditioning train were repeated samples of frozen noise, or were independent samples of noise. Using an objective procedure for measuring echo threshold, the third experiment demonstrated that both lead and lag stimuli must be presented during the conditioning train in order to produce the buildup of suppression. When only the lead sound was presented during the conditioning train, the perceptibility of the lag sound during the test burst appeared to be enhanced. PMID- 1939893 TI - The effect of frequency-selective attenuation on the speech-reception threshold of sentences in conditions of low-frequency noise. AB - Within a study on the merits of a multichannel automatic gain control in hearing aids, the effect of frequency-selective amplification on the masked speech reception threshold (SRT) for sentences is measured in conditions of seriously disturbing low-frequency noise, with the effect of wideband amplification as a reference. Speech and noise are both spectrally shaped according to the bisector line of the listener's dynamic-range of hearing, but with the noise in a single octave band (0.25-0.5 or 0.5-1 kHz) increased by 20 dB relative to this line. The increase of noise level is steady state in the first experiment, and time varying in the second experiment. Results for 12 normal-hearing and 12 hearing-impaired listeners indicate that, in both experiments, frequency-selective compression of the signal in the octave band with the 20-dB increase of noise is more beneficial than wideband compression. For the hearing-impaired group, wideband compression does not give any systematic change in intelligibility. Frequency-selective compression in steady-state conditions may, for both groups of listeners, give a decrease of masked SRT (relative to a condition without compression) of up to 4 dB for a compression factor of 100%. Roughly comparable effects are seen for frequency-selective compression in time-varying conditions. The superiority of frequency-selective over wideband compression is attributed to a more effective reduction of upward spread of masking. PMID- 1939894 TI - On the transmission of sound generated by an electromagnetic device from the mastoid process to the petrous bone. AB - An electromagnetic device (EMD) for sound transmission from the mastoid process to the petrous part of the temporal bone was designed, built, and analyzed. A theoretical model was developed in order to predict the EMD acoustical performance and the distortion caused by skull bones. This model enabled the investigation of various technical improvements and calibration options. The EMD was miniaturized by using rare earth magnets in the construction of both external transmitter and internal receiver. In vitro implantation of the internal receiver into the mastoid process was carried out by simple mastoidectomy techniques. The input and output powers of the system, including the EMD and skull bones components, were measured and the power transfer function was calculated. The sound, which was generated by the EMD and transmitted through the dry as well as simulated cadaver skull, had high fidelity in spite of some vibratory distortion at the lower sonic frequencies. Results suggest that further development of hearing aids based on electromechanical sound transmission should take into account the specific acoustic response pattern of the skull bones. PMID- 1939895 TI - An evaluation of eight computer models of mammalian inner hair-cell function. AB - Eight computer models of auditory inner hair cells have been evaluated. From an extensive literature on mammalian species, a subset of well-reported auditory nerve properties in response to tone-burst stimuli were selected and tested for in the models. This subset included tests for: (a) rate-level functions for onset and steady-state responses; (b) two-component adaptation; (c) recovery of spontaneous activity; (d) physiological forward masking; (e) additivity; and (f) frequency-limited phase locking. As models of hair-cell functioning are increasingly used as the front end of speech-recognition devices, the computational efficiency of each model was also considered. The evaluation shows that no single model completely replicates the subset of tests. Reasons are given for our favoring the Meddis model [R. Meddis, J. Acoust. Soc. Am. 83, 1056-1063 (1988)] both in terms of its good agreement with physiological data and its computational efficiency. It is concluded that this model is well suited to provide the primary input to speech recognition devices and models of central auditory processing. PMID- 1939896 TI - Discrimination of formant transition onset frequency: psychoacoustic cues at short, moderate, and long durations. AB - Two experiments determined the just noticeable difference (jnd) in onset frequency for speech formant transitions followed by a 1800-Hz steady state. Influences of transition duration (30, 45, 60, and 120 ms), transition-onset region (above or below 1800 Hz), and the rate of transition were examined. An overall improvement in discrimination with duration was observed suggesting better frequency resolution and, consequently, better use of pitch/timbre cues with longer transitions. In addition, falling transitions (with onsets above 1800 Hz) were better discriminated than rising, and changing onset to produce increments in transition rate-of-change in frequency yielded smaller jnd's than changing onset to produce decrements. The shortest transitions displayed additional rate-related effects. This last observation may be due to differences in the degree of dispersion of activity in the cochlea when high-rate transitions are effectively treated as non-time-varying, wideband events. The other results may reflect mechanisms that extract the temporal envelopes of signals: Envelope slope and magnitude differences are proposed to provide discriminative cues that supplement or supplant weaker spectrally based pitch/timbre cues for transitions in the short-to-moderate duration range. It is speculated that these cues may also support some speech perceptual decisions. PMID- 1939897 TI - Elastic models of vocal fold tissues. AB - Elastic properties of canine vocal fold tissue (muscle and mucosa) were obtained through a series of experiments conducted in vitro and were modeled mathematically. The elastic properties play a significant role in quantitative analysis of vocal fold vibrations and theory of pitch control. Samples of vocalis muscle and mucosa were dissected and prepared from dog larynges a few minutes premortem and kept in a Krebs solution at a temperature of 37 +/- 1 degrees C and a pH of 7.4 +/- 0.05. Samples of muscle tissue and mucosa were stretched and released in a slow, sinusoidal fashion. Force and displacement of the samples were measured with a dual-servo system (ergometer). After digitization, stress strain data for samples of muscle tissue and cover tissue were averaged. The stress-strain data were then fitted numerically by polynomial and exponential models. PMID- 1939898 TI - Listening bandwidths and frequency uncertainty in pure-tone signal detection. AB - The effect of frequency uncertainty on the detection of tonal signals in noise was studied using a modified probe-signal method. Widths of the listening bands used during detection were measured directly, allowing for an analysis that separates the effects of having to monitor multiple independent bands from those due to limited frequency resolution. Uncertainty was varied by beginning each trial with a cue consisting of one, two, or four randomly chosen, simultaneously presented tones. An expected signal, whose frequency matched one of the components in a cue, was presented on a majority of trials. However, on remaining trials, the signal was a probe, which meant that its frequency differed from one of the components in the cue by a constant ratio. Performance as measured in percent correct declined for probes at increasingly distant ratios from the expected values. The results were converted to dB using individual psychometric functions for expected signals and listening bands were fitted using the rounded exponential filter of Patterson et al. [J. Acoust. Soc. Am. 72, 1788-1803 (1982)]. The obtained bandwidths are comparable to those reported using notched noise maskers, but there is a small but consistent increase in bandwidth with increased numbers of components in the cues. The primary results is that the effects due to uncertainty are well described by a 1-of-M orthogonal band model, which takes into consideration limitations of the detector, including the widths of the listening bands. PMID- 1939899 TI - Evaluation of simple models of auditory profile analysis using random reference spectra. AB - This article describes further study of the finding reported by Green et al. [J. Acoust. Soc. Am. 73, 639-643 (1983)] and others that, in certain conditions, the threshold of detectability for an intensity increment to the center tone of a multitone reference spectrum decreased as the number of nonsignal tones increased. That result was considered remarkable since critical-band theory would predict that these nonsignal tones, spaced outside the "critical band" containing the signal, would have no effect on or, at most, slightly decrease within-band detectability--and certainly could not account for the result of improved detectability found in the study cited above. Recently, Henn and Turner [J. Acoust. Soc. Am. 88, 126-131 (1990)] were unable to replicate the result described above, concluding that the phenomenon exists only in "limited conditions" and that is "highly individual" in nature. Further, they speculated that the most likely reason for the discrepancy between their study and previous studies was the selection and/or training of the observers. The present study addressed the effects of the amount of subject training on the finding of Green et al. while controlling the potential effects of stimulus order. Specifically, for a group of three "naive" listeners, thresholds were measured for 3-, 7-, and 21-tone inharmonic complexes as a function of the amount of practice in a mixed block design. In all cases the group mean thresholds decreased as the number of nonsignal tones increased both initially and after extensive practice for both fixed- and roving-level conditions. Thus the effect does not appear to be an artifact of the amount or order of training subjects receive. The possible role of subject sample size and the magnitude of individual differences in obtaining the effect remains an open question. Two hypotheses suggested to account for the improvement in threshold with increasing number of nonsignal tones were evaluated. The hypotheses were represented by simple mathematical models, referred to as the "multiple-comparison" and "pitch-cue" models. The predictions of both models were compared with the results of a series of detection experiments in which the independent variables were the number of nonsignal tones and amount of random, within-trial "amplitude perturbation" [cf. Kidd et al., J. Acoust. Soc. Am. 79, 1045-1053 (1986)] of the nonsignal tones. Neither model, as applied, provided a satisfactory account of the effects of the main variables of number of tones and amount of perturbation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1939900 TI - Free-field release from masking. AB - Free-field release from masking was studied as a function of the spatial separation of a signal and masker in a two-interval, forced-choice (2IFC) adaptive paradigm. The signal was a 250-ms train of clicks (100/s) generated by filtering 50-microseconds pulses with a TDH-49 speaker (0.9 to 9.0 kHz). The masker was continuous broadband (0.7 to 11 kHz) white noise presented at a level of 44 dBA measured at the position of the subject's head. In experiment I, masked and absolute thresholds were measured for 36 signal source locations (10 degree increments) along the horizontal plane as a function of seven masking source locations (30 degree increments). In experiment II, both absolute and masked thresholds were measured for seven signal locations along three vertical planes located at azimuthal rotations of 0 degrees (median vertical plane), 45 degrees, and 90 degrees. In experiment III, monaural absolute and masked thresholds were measured for various signal-masker configurations. Masking-level differences (MLDs) were computed relative to the condition where the signal and mask were in front of the subjects after using absolute thresholds to account for differences in the signal's sound-pressure level (SPL) due to direction. Maximum MLDs were 15 dB along the horizontal plane, 8 dB along the vertical, and 9 dB under monaural conditions. PMID- 1939902 TI - Comodulation masking release over a three octave range. PMID- 1939901 TI - Psychometric functions for level discrimination. AB - To determine the form of psychometric functions for 2I,2AFC level discrimination (commonly called intensity discrimination), ten increment levels were presented in random order within blocks of 100 trials. Stimuli were chosen to encompass a wide range of conditions and difference limens: eight 10-ms tones had frequencies of 0.25, 1, 8, or 14 kHz and levels of 30, 60, or 90 dB SPL; two 500-ms stimuli also were tested: a 1-kHz tone at 90 dB SPL and broadband noise at 63 dB SPL. For each condition, at least 20 blocks were presented in mixed order. Results for five normal listeners show that the sensitivity, d', is nearly proportional to delta L (= 20 log [(p + delta p)/p], where p is sound pressure) over the entire range of difference limens. When d' is plotted against Weber fractions for sound pressure, delta p/p, or intensity, delta I/I, exponents of the best-fitting power functions decrease with increasing difference limens and are less than unity for large difference limens. The approximately proportional relation between d' and delta L agrees with modern multichannel models of level discrimination and with psychometric functions derived for single auditory-nerve fibers. The results also support the notion that the difference limen, expressed as delta LDL and plotted on a logarithmic scale, is an appropriate representation of performance in level discrimination experiments. PMID- 1939903 TI - An interleaved tracking procedure to monitor unstable psychometric functions. AB - In some experimental situations, the psychometric function underlying performance may not be stable, but instead may shift along the stimulus axis in response to changes in attention, learning, or task difficulty. When this occurs, the measured threshold may be influenced and the slope of the measured function will be inaccurately shallow. With commonly used experimental procedures, it is difficult to know whether a shallow psychometric function slope is a true reflection of the sensory process, or is a result of "averaging" a highly variable underlying function. Here, a new method is described of estimating psychometric function slope from the variability in two interleaved adaptive tracks, consulted on alternate trials, that is resistant to the effects of shifting performance levels. Further, a mechanism is described for assessing the likelihood that a threshold was, in fact, stable over the course of its measurement. Computer simulations are reported as well as verification of the method in measurements of human performance on a psychophysical task. Several conditions of externally imposed variability were simulated to establish the ability of these procedures to identify unstable functions and produce accurate slope estimates. The procedures worked well for thresholds shifting by as little as 4 dB if the variation did not occur too rapidly. The procedure and associated analyses are recommended as a relatively "free" means of calculating slope and quantifying threshold reliability with little extra experimental effort. PMID- 1939904 TI - Human brain-stem auditory evoked responses obtained by cross correlation to trains of clicks, noise bursts, and tone bursts. AB - Brain-stem auditory evoked responses (BAERs) were obtained in eight normal hearing young adults. Stimuli included clicks, noise bursts, and tone bursts. Tone bursts included carrier frequencies of 1, 2, 4, and 8 kHz. All stimuli were presented at 60 dB nHL. BAERs were obtained by presenting stimuli in pseudorandom trains, called maximum length sequences (MLSs). BAERs were recovered by cross correlating the responses with a recovery sequence. MLS-BAERs were obtained with minimum pulse intervals (MPIs) of 6, 4, and 2 ms. Conventional BAERs were also obtained for stimuli presented at a rate of 30 Hz. BAERs were obtained for all stimuli, for both the conventional averaging technique and for the cross correlation technique. BAERs were observed for MPIs as short as 2 ms for all stimuli. Wave V was the only peak consistently identifiable for these stimuli. For all stimuli, wave V latency increased and wave V amplitude decreased with decreasing MPI. This is the first demonstration of the use of maximum length sequences combined with cross correlation to obtain BAERs to noise burst and tone burst stimuli. PMID- 1939905 TI - Effects of relative starting phase and frequency separation of two-tone stimuli on the brain-stem auditory-evoked response. AB - Brain-stem auditory-evoked responses (BAERs) were obtained in six normal-hearing adults using single-tone and two-tone stimuli arithmetically centered around 4000 Hz. Two-tone stimuli varied in frequency separation from 200 to 3200 Hz, and started in-phase (homophasic) or 180 deg out-of-phase (antiphasic) with each other. Responses to each of the single-tone components of the two-tone stimuli were elicited and then summed for comparison with responses to the two-tone stimuli. Results indicated no significant difference in wave V latency between homophasic or antiphasic two-tone conditions, and summed single-tone conditions. Under the homophasic condition, the mean latency for the widest frequency separation of the tones was significantly longer than those for narrower separations. A significant difference in wave V amplitude between two-tone phase conditions was found for frequency separations of 200, 400, and 3200 Hz only. Summed single-tone BAERs demonstrated a significantly larger wave V amplitude than responses from either two-tone phase condition at all frequency separations. PMID- 1939906 TI - Focalization: environmental focusing and source localization. AB - Conventional matched-field processing (MFP) requires accurate knowledge of the ocean-acoustic environment. Focalization, which simultaneously focuses and localizes, eliminates this stringent requirement by including the environment in the parameter search space. This generalization of MFP involves defining an appropriate high-resolution cost function, parametrizing the search space of the environment and source, constructing solutions of the wave equation, and utilizing a nonlinear optimization method to search the parameter landscape for the global minimum of the cost function. Focalization is implemented using cost functions based on ray theory and wave theory, empirical orthogonal functions for the environmental description, and simulated annealing for optimization. Numerical simulations are presented to demonstrate the feasibility of focalization. PMID- 1939908 TI - Acoustic microcavitation: its active and passive acoustic detection. AB - In this work acoustic microcavitation in water is studied primarily at 0.75 MHz and 1% duty cycle. To detect cavitation, two kinds of acoustic detectors are used. The first one is an unfocused, untuned 1-MHz receiver transducer that serves as a passive detector. The other one is a focused 30-MHz transducer that is used in pulse-echo mode and is called the active detector. Cavitation itself is brought about by a focused PZT-8 crystal driven in pulse mode. The active detector is arranged confocally with respect to the cavitation transducer. Both the interrogating pulse and the cavitation pulse arrive simultaneously at the common focus, which is the region of cavitation. With the test chamber filled with clean water, no cavitation is observed, even when the cavitation transducer is driven to give its peak output of 22 bar peak negative. Cavitation is, however, observed when polystyrene microparticles are added to the host water. Our view of how these smooth, spherical, monodispersed microparticles give rise to cavitation is described with some estimates. An attempt has been made to understand whether the presence of "streaming" affects the thresholds, and it has been found that the active detector field affects the cavitation process. PMID- 1939907 TI - Acoustic microcavitation: enhancement and applications. AB - Experimental investigation into acoustic microcavitation is extended to include "cavitation activity" in addition to the threshold measurements using acoustic detectors. The primary setup incorporates two detectors: an unfocused, untuned 1 MHz transducer, which serves as a passive detector, and a focused 30-MHz transducer used in pulse-echo mode as the active detector. Cavitation itself is brought about by a focused piezoelectric transducer driven in pulse mode. The active detector is arranged confocally with respect to the cavitation transducer. Both the interrogating pulse and the cavitation pulse arrive simultaneously at the common focus which is the region of cavitation. Cavitation is conducted primarily at 0.75 MHz and 1% duty cycle in clean water using microparticles to seed the events. Cavitation activity appears to be directly proportional to the number density of the particles present in the cavitation medium. The fact that the active detector affects the cavitation process can be further exploited to seek interesting applications leading possibly to submicronic particle counting and testing of surface characteristics of silica particles used in liquid chromatography. PMID- 1939909 TI - Spherical-wave expansions of piston-radiator fields. AB - Simple spherical-wave expansions of the continuous-wave fields of a circular piston radiator in a rigid baffle are derived. These expansions are valid throughout the illuminated half-space and are useful for efficient numerical computation in the near-field region. Multipole coefficients are given by closed form expressions which can be evaluated recursively. PMID- 1939911 TI - Postlingual deaf speech and the role of audition in speech production: comments on Waldstein's paper [R.S. Waldstein, J. Acoust. Soc. Am. 88, 2099-2114 (1990)]. AB - Using acoustic analysis techniques, Waldstein [J. Acoust. Soc. Am. 88, 2099-2114 (1990] reported abnormal speech findings in postlingual deaf speakers. She interpreted her findings to suggest that auditory feedback is important in motor speech control. However, it is argued here that Waldstein's interpretation may be unwarranted without addressing the possibility of neurologic deficits (e.g., dysarthria) as confounding (or even primary) causes of the abnormal speech in her subjects. PMID- 1939910 TI - A datalogger to identify vocalizing dolphins. AB - A datalogger was developed to identify vocalizing dolphins within socially interacting captive groups. Every 50 ms the logger stores data on the level and frequency of detected sound. Dataloggers are temporarily attached to dolphins by suction cups for data collection sessions lasting up to 45 min. Later, computer analysis of data from the dataloggers reveals which dolphin produced each vocalization recorded during the session. Results from use of dataloggers with two captive bottlenose dolphins (Tursiops truncatus) at the New England Aquarium in Boston, MA are presented. The possible use of dataloggers with wild dolphins is discussed. PMID- 1939912 TI - Analytic and synthetic pitch of two-tone complexes. AB - An experiment was performed in which subjects had to judge whether the pitch of two sequential sounds went up or down. The sounds were harmonic two-tone complexes. They were constructed in such a way that the frequency of one harmonic remained fixed, the frequency of the other went up or down, and the missing fundamental moved in the opposite direction. Results show that, for partials of low harmonic order, most subjects tend to follow the frequency of the moving partial, whereas for partials of order 6 or higher, responses are divided more or less equally between tracking of the moving partial and tracking of the missing fundamental. PMID- 1939913 TI - Helping people who want to stop smoking. PMID- 1939914 TI - Assessing patients' pain: identifying reasons for error. AB - Accurate pain assessment is vital for good medical care, and yet the literature indicates that nurses often provide inaccurate and biased estimates of their patients' pain. The following paper reviews the methods used to assess nurses' accuracy, and reasons offered for the errors observed. Practical options for improving pain assessment and pain management are discussed. PMID- 1939915 TI - Myocardial infarction survivors: age and gender differences in physical health, psychosocial state and regimen adherence. AB - Little is known about women's and older adults' experiences after myocardial infarction (MI). The purpose of this study was to determine if gender and age differences exist in psychosocial condition, health state and therapeutic regimen adherence among MI survivors. Adults aged 40 to 88 years (n = 197) were interviewed 1 to 2 years after their first MI. The Profile of Mood States was used to measure anxiety and depression, the Personal Resources Questionnaire was used to measure social support, the Rosenberg Self-Esteem scale was used to measure self-esteem, the Perceived Quality of Life scale was used to measure quality of life, and the Health Behaviour Scale was used to assess therapeutic regimen adherence. Cardiac rehabilitation participation was recorded from rehabilitation centre records. Subjective health appraisals were assessed using investigator-developed questions. Increased age was associated with higher depression scores, lower quality of life, less social support, less participation in formal cardiac rehabilitation, less therapeutic exercise and poorer general health. Women reported poorer health than men. Findings indicated older males may be at risk for lower social support and continued smoking after infarction. These findings suggest that the often-reported experience of middle-aged males post-MI cannot be generalized to all adults experiencing infarction. PMID- 1939916 TI - Quality of life after organ transplantation. AB - Organ transplants are being conducted with increasing frequency. It is generally known that these procedures increase length of life, but less is known about the quality of that life. In this paper, the literature pertaining to quality of life of patients with kidney, pancreas, heart, heart-lung, liver and bone marrow transplants is reviewed. On the basis of this review, it seems that quality of life after kidney and heart transplantation is very good, when compared to the pretransplant state. However, more research is required to examine quality of life of recipients of other types of transplantation. There are many issues that pertain to measurement of quality of life that remain to be addressed. These include: definitions of quality of life, dimensions of quality of life, expectations of quality of life and clinical assessment of quality of life. PMID- 1939917 TI - Attitudes toward nurses discussing sexual concerns with patients. AB - Attitudes toward nurses discussing sexual concerns with clients were examined in 73 healthy subjects using Section A of the Sexual Adjustment Questionnaire. The variables of age, sex, race, occupation, educational level, marital status, importance of sexual activity, frequency of discussing sexual relationship with partner, and number of others with whom sexual concerns are discussed were examined to determine influence on subject's attitudes. Ninety-two per cent of subjects thought that nurses should discuss sexual concerns with clients. Weighted least squares analysis showed that only two variables (number of others with whom sexual concerns are discussed and race) were significant predictors of attitudes. PMID- 1939918 TI - The theory-practice gap in nurse education: its causes and possible solutions. Findings from an action research study. AB - Kurt Lewin, the originator of action research, proposed that it was valuable not only for innovating change, but also the process of change could lead to new insights into the nature of the problem that was being tackled. This action research project developed and evaluated a teaching model that aimed to help RGN (registered general nurse) students to bridge the theory-practice gap. During the course of this work, the possible reasons for a theory-practice gap started to become clear. This paper provides a discussion of these factors. The viewpoint for this discussion is that of the student nurse. The student is assumed to 'own' the problem and it is from her perspective that the theory-practice gap is analysed. The paper includes a critical examination of books, lectures, the school curriculum and ward nursing practice. Finally, possible solutions to the theory-practice problem are discussed and it is hoped that these will provide a rational basis for tackling the problem. PMID- 1939919 TI - How accurately do nurses perceive patients' needs? A comparison of general and psychiatric settings. AB - This paper examines to what extent nurses' perceptions of patients' needs correspond to the patients' views of their own needs. A questionnaire was designed to assess patients' emotional and physical needs in general medical wards and in acute psychiatric wards. Sixty patients, 30 psychiatric and 30 general, together with their 'key' nurses, took part in the study. Results indicate that, despite there being no evidence of appreciable disagreement between the 'average' psychiatric nurse and the 'average' psychiatric patient, there is little evidence that individual nurses and their patients, whether psychiatric or general, agree. The nurses' inability to perceive patients' needs on an individual basis is consistent with other studies which suggest that nurses use stereotypes when perceiving patients' needs. Implications for nursing care are discussed. PMID- 1939920 TI - The prevalence of psychiatric morbidity on a coronary care ward. AB - Numerous studies have documented the high prevalence of psychological and emotional disorders in patients seen in general medical settings. However, despite the emphasis placed on holistic approaches to nursing care in all professional models of nursing practice, much of this distress is still missed by nursing staff. The Hospital Anxiety and Depression (HAD) scale is an easy-to-use self-administered screening instrument purportedly designed to detect psychological distress amongst hospitalized patients with physical illnesses. On using the HAD scale on patients admitted to a coronary care ward of a district general hospital, 44% were found to be suffering high levels of anxiety or depression. This figure is consistent with the results of similar studies in other cardiac wards and out-patient clinics. In most cases, the levels of distress found were not sufficiently severe to warrant seeking specialist psychiatric support. Instead, there is much that the general nurse can do to alleviate the understandable fears and worries of patients being treated for cardiac disease. However, to respond appropriately, nursing staff must be able to identify psychological distress in patients. The HAD scale, if it can be validated in cardiac in-patient settings, provides an instrument which could easily become part of the routine assessment of patients' nursing needs. PMID- 1939921 TI - The stressors and strains of health visiting: demands, supports, constraints and psychological health. AB - An empirical study investigated the work stressors and psychological strains experienced by health visitors in three areas of Hertfordshire and Bedfordshire. A questionnaire, based on Payne's model of occupational stress, probed the perceived demands, supports and constraints of the work and the coping strategies used by the health visitors. The research aimed to establish the extent and nature of strain using validated indicators of general anxiety and depression, to pinpoint specific features of the work which are associated with the strain measures, and to suggest possible changes to working practices. While health visitors found their jobs generally satisfying, a significant number of staff were under strain even though the mean levels of strain were lower than those observed in social workers and hospital-based nursing staff working with people who have a mental handicap, and little different from women who work in industry. Many aspects of the job were perceived to be demanding yet the demanding nature of cases was not related to strain measures. There were, however, interesting statistical relationships between strain scores and demands concerned with colleagues and managers and the amount of support a health visitor perceived. PMID- 1939922 TI - The Burford Nursing Development Unit holistic model of nursing practice. AB - This paper offers a new approach for developing a model of nursing emerging from and hence inherently compatible with a philosophy for practice. It builds on the author's earlier work of describing a paradigm for writing a philosophy for practice. The model is that of the Burford Nursing Development Unit in Oxfordshire, England. PMID- 1939923 TI - The failure of exposure treatment in agoraphobia: implications for the practice of nurse therapists and community psychiatric nurses. AB - There are no systematic studies of the failure of psychiatric nursing interventions and few very such studies in the psychological/psychiatric outcome literature. This study reports a controlled study of exposure treatment with agoraphobic clients who were treated by nurse therapists and psychologists. This includes an analysis of the four categories of treatment failure (i.e. treatment refusers, treatment dropouts, failures and relapsers). The analysis consisted of an examination of the outcome data of clients who met a priori criteria for the categories of failure and an examination of questionnaire responses. The results have implications for psychiatric nursing practice, particularly with regard to preparation for treatment. Additionally, the results indicate that much more research needs to be carried out on treatment methods and that exposure alone produces a significant but limited effect. Finally, the paper suggests that outcome research is a priority in psychiatric nursing. PMID- 1939924 TI - A study of the teaching and learning of the biological sciences in nurse education. AB - The study was designed to explore the teaching and learning of the biological sciences in nurse education in an attempt to identify why some students are failing to support their practice with theory. Questionnaires were sent to third year nurse students (n = 140) and nurse teachers (n = 43) in three schools of nursing. Several findings emerged from the study: (a) the balance between the behavioural and biological sciences in nurse education was perceived by the students as being too much in favour of the behavioural sciences; (b) the level of knowledge from the biological science taught was perceived by the students as being inappropriate for RGN training; (c) teachers felt inadequately prepared to teach the biological sciences and, similarly, nurse students felt inadequately prepared in these sciences; and (d) self-directed methods of teaching and learning, although used most frequently, were perceived by the students as being the most ineffective. PMID- 1939925 TI - An analysis of the concept of experience. AB - This paper is an analysis of the concept of experience. It begins with an examination of some of the methods used in concept analysis. Following this, an eclectic approach is taken by the combination of many aspects from some of the analysis methods discussed. It shows that the term experience is used in four ways in normal nursing usage: exposure to a particular event, emotion, information or situation; time spent in the service of nursing; the amount of knowledge gained over a period of time; and an event, situation or emotion. Various methods are used then to define experience and to delineate the meaning of experience in the profession of nursing. It is made clear that the measurement of experience in quantitative terms is widespread, but that measurement in qualitative terms is less well understood, but may prove to be more important. PMID- 1939927 TI - Health systems and policy in the USA and in the United Kingdom: an overseas programme. AB - An international programme, especially in a developed country, dramatically increases a student's understanding of health care systems. Students from a university programme in the USA learn about the development and structure of the British National Health Service through lectures and discussion in the US and England, and through 2 weeks of experience in England which include working with community health nurses in a district health authority. Related special experiences are planned which may include interviews with nurses involved in policy development, education, administration and specialty areas. Each student identifies an interest to pursue independently from the perspective of community care. As the student participates in the programme, alternative ways to give familiar care challenge formerly held beliefs. Health care emerges as a dynamic system, one that responds to issues, effects policy, and influences the role of health care providers. PMID- 1939926 TI - An evaluation of the Johnson Behavioural System Model of Nursing. AB - In this paper the authors evaluate the Johnson Behavioural System Model of Nursing by applying the assessment criteria described in an earlier paper. Data for the evaluation were collected by one of the authors (W.R.) at the UCLA Neuropsychiatric Institute and Hospital, and the UCLA School of Nursing, Los Angeles. The major focus of this paper relates to how nurses at the above facilities apply the Johnson Behavioural System Model of Nursing and how that relates to the questions posed in a previous paper which should be asked by clinicians when assessing the relevance of a model to clinical nursing practice: namely, (a) to what extent does the model assist with the identification of the range of human responses to actual or potential health problems? (b) How does the model enable a nursing diagnosis to be made, and what is the basis of that diagnosis? (c) Does the model explain why individuals respond to health problems in the way that they do? (d) Does the model inform clinicians of the nursing interventions required to enable the client to move towards optimum health? (e) Does the model help to provide an understanding of the desired outcome of nursing intervention? PMID- 1939928 TI - The temporal onset of individual symptoms in winter depression: differentiating underlying mechanisms. AB - The transition from well to depressed offers a window to the mechanisms which underlie depressive symptoms. We examined the onset of each of 15 symptoms in 53 patients with winter depression. Three symptoms had a risk of onset closely associated with the onset of the episode itself and may represent a core syndrome. The risk of onset for the remaining symptoms was unrelated to the onset and the course of the episode. The symptoms were equally likely to begin at any time during the episode and suggest a different pathological mechanism. A dual vulnerability hypothesis is proposed; research and treatment implications are discussed. PMID- 1939929 TI - Major depression and personality disorder. AB - The authors examined an interview and paper-and-pencil assessment of the DSM-III personality disorders (PDs) in depressed inpatients, and depressed relatives of psychiatric patients and never-ill controls who had a lifetime history of major depression. The rates of PDs according to the Structured Interview for DSM-III Personality Disorders (SIDP) were similar in the two groups, except for borderline PD which was more frequent in the inpatients. Of the individuals with a PD, the patients were more likely than the relatives to have two or more PDs, and the borderline and histrionic patients were more prototypic of these disorders than were the borderline and histrionic relatives. In contrast to the SIDP results, the rates of PDs according to the Personality Disorders Questionnaire (PDQ) were higher in the patient sample. These results thus extend the previously described high rates of PDs in depressed patients to a sample of individuals with a lifetime history of treated or untreated depression, and they suggest that interview assessments of personality may be less sensitive to the state effects of depression than are questionnaires. PMID- 1939930 TI - The development and descriptive use of the Lithium Attitudes Questionnaire. AB - Studies of patients' attitudes towards lithium treatment are reviewed. In the present work, a brief questionnaire was developed as a means of identifying and grouping the problems patients commonly have with taking lithium regularly. This 'Lithium Attitudes Questionnaire' was found to yield consistent results which patients later confirmed at interview. It was also evaluated in relation to assessments patients made, prior to its first administration, of the main advantages and disadvantages of lithium treatment. Its subscores were then used to describe patients who expressed opposition to continuing on lithium, and those who missed their hypomanic episodes. PMID- 1939931 TI - Further exploration of the relationship between depression and dependence. AB - Two instruments, the Self Rating Questionnaire and the Interpersonal Dependency Inventory, were used to examine further the relationship between dependence and depression. Dependence scores on both measures correlated highly with scores on measures of neuroticism, self-esteem, depressive cognition and depression. Dependence scores were significantly higher in samples of depressed subjects than in samples of non-depressed subjects. The scores of depressives who fully recovered dropped, but those of depressives who remained depressed or who only partially recovered remained high. In non-depressed subjects there was no relationship between dependence and gender. There was no support for the use of subscales of dependence. PMID- 1939932 TI - MMPI measures of impulsivity and depression correlate with CSF 5-HIAA and HVA in depression but not schizophrenia. AB - Recent studies have linked impulsivity with CSF concentrations of both 5 hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA). One work found a negative correlation between the MMPI psychopathic deviate (Pd) scale and 5-HIAA in personality disordered men (Brown et al., 1982). We found that the 5-HIAA/Pd correlation extends (P less than 0.05) to unmedicated depressed patients (n = 21). A trend was found between HVA and Pd in depression. There was no relationship between either metabolite and the Pd scale in unmedicated schizophrenics (n = 24). A significant inverse correlation was found between the MMPI depression scale and CSF HVA but not 5-HIAA in the depressed patients. PMID- 1939933 TI - The course of a seasonal bipolar disorder influenced by caffeine. AB - A longitudinal case report shows a sudden remission of the severe course of a seasonal bipolar disorder after 10 years of psychopharmacological treatments. The discontinuation of heavy caffeine intake appears to have contributed to the outcome. PMID- 1939934 TI - Time to move forward: an agenda for campus sexual health promotion in the next decade. PMID- 1939935 TI - College student's perceptions of sources of information about AIDS. AB - Public communication campaigns and social marketing literature identify principles for developing effective AIDS education and prevention efforts. Planners need to know the audience, identify salient audience segments, and understand the characteristics of information sources that the particular audience finds believable and is likely to use. In this study, the authors investigated college students' perceptions of (1) the credibility and likelihood of using a variety of interpersonal, media, and institutional sources of information about AIDS; (2) the sources that have provided them with the most information about AIDS; and (3) the relationships among those perceptions. They also investigated potential gender differences in perceptions of sources of AIDS information. Respondents to a larger probability sample survey rated 35 sources of information about AIDS. Although mass media sources clearly provided the greatest amount of information, they were conspicuously less prominent in their acceptability to respondents. Leaflets were the only kinds of media sources that the respondents rated high on both believability and likelihood of use. In contrast, three interpersonal sources and four institutional sources appeared as best choices on the combined criteria. Results are discussed in terms of implications for planning and implementing AIDS education and prevention programs for the college-student audience. PMID- 1939936 TI - Student and faculty knowledge, attitudes, and behaviors related to AIDS: implications for health educators. AB - Results of a random survey of university faculty and students regarding their knowledge, behavior, and attitudes concerning AIDS are reported. The majority of faculty and students held enlightened views of AIDS. Faculty, however, tended to be better informed than students in a number of areas. These findings are consistent with results of surveys of students at two other universities. Implications for health educators are discussed. PMID- 1939937 TI - Effects of a peer-led AIDS intervention with university students. AB - Acquired immune deficiency syndrome (AIDS) has become a major health threat to university students. This study evaluated a peer-led AIDS intervention program with university students (1) increase knowledge of human immunodeficiency virus (HIV) transmission and infection; (2) change attitudes to reflect scientific information on AIDS-related facts; and (3) change behavioral intentions to correspond with safer sexual practices. Subjects were students (N = 142) from four undergraduate classes and were predominantly female (65%), white (82%), and sexually active (86%). A non-equivalent control group design was used, with two classes receiving the intervention and two classes receiving no information. For the intervention, peer educators presented AIDS-related information, modeled ways to use condoms safely and ways to discuss condom use with sexual partners, and led discussions on HIV infection and use with sexual partners, and led discussions on HIV infection and AIDS, relationships, sexuality, and condom use. A questionnaire was administered to assess differential changes in AIDS-related knowledge, attitudes, and behavioral intentions between the intervention and control groups. The results showed significant improvements among intervention subjects on the knowledge, attitudes, and behavioral intentions scales compared with the control group. PMID- 1939938 TI - Barrier versus oral contraceptive use: a study of female college students. AB - Although they provide birth control and are easier to use, oral contraceptives (OCPs) are not the preferred approach to preventing sexually transmitted disease (STD). Do the knowledge, attitudes, and experiences of oral contraceptive users place them at greater risk for STDs than those who employ barrier methods? This study examined differences between sexually active female college students (ie, those who reported ever having had vaginal intercourse) who used OCPs and those who employed barrier methods of contraception at the time of their most recent intercourse. The authors analyzed HIV- and other STD-related knowledge, attitudes, and behaviors from three consecutive annual health surveys of young women about to begin their first year of college. Findings showed barrier and OCP users to be comparable in knowledge about the effectiveness of various contraceptive methods in protecting them against STDs, perceived personal susceptibility to HIV, and experiences with alcohol before sexual intercourse. Oral contraceptive users, compared with those in the group who used barrier methods, reported a greater number of recent partners (p less than .03) and greater perceived vulnerability to STDs (p less than .03). Student healthcare providers must develop creative educational strategies to encourage simultaneous use of both oral contraceptives and barrier methods to protect students against STDs and pregnancy. PMID- 1939939 TI - What is the impact of a campus AIDS education course? AB - To meet a graduation requirement at a state university, 225 students took a 1 semester interdisciplinary course on AIDS. In addition to lectures, readings, and recitation sections, all the students participated in three small-group discussions of their feelings on AIDS-related issues. Students in other courses at the same university served as controls. Anonymous questionnaires were administered before and after the course to assess changes in knowledge, attitudes, and behaviors related to AIDS. When compared with the control group, students in the course had become more knowledgeable about the disease, less fearful of AIDS, and less homophobic. They perceived the AIDS epidemic as more severe than they did before the course, but they were more likely to believe that effective preventive measures were possible. They were also more likely to believe that others in their peer group were taking action to prevent HIV infection. There was no significant increase in either the experimental or the control group in the students' belief that they were personally vulnerable to AIDS, nor was there any statistically significant change in AIDS-related sexual or drug-abuse behaviors. PMID- 1939940 TI - Development of a classroom-based AIDS education program at a New Jersey State College. PMID- 1939941 TI - Is value-free sex talk valuable? PMID- 1939942 TI - Recommended guidelines for in-hospital cardiac monitoring of adults for detection of arrhythmia. Emergency Cardiac Care Committee members. PMID- 1939943 TI - Events in the cardiac arrhythmia suppression trial: baseline predictors of mortality in placebo-treated patients. AB - Patients randomized to placebo in the encainide and flecainide arms of the Cardiac Arrhythmia Suppression Trial (CAST) have been found to have a relatively low 1-year mortality rate of 3.9% in comparison with previous studies of patients in the postmyocardial infarction period. To determine the comparability of CAST with previous studies, baseline variables were examined in the 743 patients randomized to placebo in the flecainide and encainide arms of CAST. Twenty-three baseline characteristics were correlated with major outcome events: arrhythmic death (16 events), total mortality (26 events) and congestive heart failure (51 events). On multivariate analysis the risk of new or worsening congestive heart failure was significantly associated with diuretic use, diabetes, high New York Heart Association functional class, age, prolonged QRS duration and low ejection fraction. The risk of arrhythmic death or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, history of heart failure, use of digitalis, diabetes and prolonged QRS duration. Total mortality or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, diabetes, ST segment depression, high functional class, prolonged QRS duration and low ejection fraction. The variables at baseline associated with mortality from all causes or arrhythmic death or resuscitated cardiac arrest and heart failure in the CAST placebo-treated patients are similar to those identified in previous postmyocardial infarction studies. Thus, the observation of increased mortality in CAST associated with the administration of encainide and flecainide for suppression of ventricular premature depolarizations is probably applicable to any comparably defined group of patients in the postmyocardial infarction period. PMID- 1939944 TI - Effect of intracoronary stenting on intimal dissection after balloon angioplasty: results of quantitative and qualitative coronary analysis. AB - The effect of the Palmaz-Schatz stent on the angiographic appearance and residual luminal stenosis in patients with intimal dissection after balloon angioplasty was evaluated in 84 consecutive patients (90 lesions). Coronary angiography was performed before angioplasty, after conventional angioplasty and after stent implantation. The degree of intimal disruption was assessed as follows: grade 0, no dissection; grade 1, simple dissection (intraluminal linear defect or extraluminal cap extravasation); or grade 2, complex dissection (nonlinear spiral defect or luminal defect with multiple irregular borders). Quantitative coronary analysis of digitized cineangiograms was performed with use of a computerized automatic edge detection algorithm. After balloon angioplasty, 31 (34%) of 90 lesions demonstrated intimal dissection (18 simple, 13 complex). After stent implantation, intimal dissection improved by greater than or equal to 1 grade in 29 (94%) of the 31 lesions with 27 (87%) reduced to grade 0 (that is, no dissection). Dissection grade improved after stenting in 16 (89%) of 18 simple dissections and in all 13 complex dissections. Mean diameter stenosis was 77 +/- 17% before angioplasty, 47 +/- 17% after angioplasty and 14 +/- 10% after stenting (before angioplasty vs. after angioplasty and after angioplasty vs. after stenting, p less than 0.0001). In conclusion, intracoronary stenting is effective in reducing the residual luminal stenosis and in improving the angiographic appearance of intimal dissections after conventional balloon angioplasty. PMID- 1939945 TI - Diagnosis of acute pulmonary embolism in the elderly. AB - The diagnostic features of acute pulmonary embolism among 72 patients greater than or equal to 70 years old were evaluated and compared with characteristics of pulmonary embolism among 144 patients 40 to 69 years and 44 patients less than 40 years old. Syndromes characterized by either 1) pleuritic pain or hemoptysis, 2) isolated dyspnea, or 3) circulatory collapse were observed with comparable frequency among patients greater than or equal to 70 years old and younger patients. One of these presenting syndromes occurred in 64 (89%) of the 72 patients greater than or equal to 70 years old. Those who did not show these syndromes were identified on the basis of unexpected radiographic abnormalities, which may have been accompanied by tachypnea or a history of thrombophlebitis. Among the 72 patients greater than or equal to 70 years with pulmonary embolism, dyspnea or tachypnea (respirations greater than or equal to 20/min) occurred in 66 (92%), dyspnea or tachypnea or pleuritic pain in 68 (94%) and dyspnea or tachypnea or radiographic evidence of atelectasis or a parenchymal abnormality in 72 (100%). Complications of angiography were evaluated among patients with and without pulmonary embolism. Major complications of pulmonary angiography among patients greater than or equal to 70 years old (2 [1%] of 200) were not more frequent than among younger patients (6 [1.1%] of 562) (p = NS). However, renal failure (major or minor) was more frequent in patients greater than or equal to 70 years old than in younger patients (6 [3%] of 200 versus 4 [0.7%] of 562) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939946 TI - Clinical and angiographic characteristics and outcome of patients with rest unstable angina occurring during regular aspirin use. AB - Today many patients admitted with an acute coronary syndrome are already taking aspirin. Because they have symptoms despite antithrombotic therapy, these patients are presumed to be at higher risk for subsequent clinical events. In a pilot trial of antithrombotic therapy in patients with unstable angina at rest or non-Q wave infarction, 93 patients admitted within 48 h of pain were prospectively followed up for 12 weeks. On admission, 29 patients (31%) were already taking daily aspirin; 64 (68%) were receiving no antiplatelet agent. After enrollment all patients received antithrombotic therapy with either aspirin or heparin according to protocol regardless of prior aspirin use. The two groups (prior users versus nonusers of aspirin) were similar with regard to age, gender, coronary risk factors, prior antianginal medication, duration of symptomatic coronary disease, presentation with non-Q wave infarction and extent of electrocardiographic changes on admission. Quantitative analysis of coronary arteriograms (on a 0 to 10 scale) showed similar myocardium-in-jeopardy scores (JS). Follow-up events (recurrent ischemia [Isch], infarction [MI] and revascularization [Revasc]) were: (formula: see text) Aspirin users experiencing rest angina are similar to other patients with ischemic rest pain. The "resistant to aspirin" group does not constitute a subgroup that is at higher risk for cardiac events or revascularization. PMID- 1939947 TI - Absence of myocardial dysfunction during stress in patients with syndrome X. AB - Stress two-dimensional echocardiographic studies were performed in 18 patients with angina, a positive exercise test and normal findings on coronary angiography (syndrome X). Rest and immediate posttreadmill exercise two-dimensional echocardiograms were performed with a digitized cine loop and side by side visual analysis in all patients. In 16 of these patients, right atrial pacing up to 160 beats/min was also performed and percent systolic wall thickening was calculated at five equally spaced segments around the left ventricle, each corresponding to an anterior, lateral and inferior wall and the posterior and the anterior ventricular septum. Measurements of percent systolic wall thickening were established in 10 age- and gender-matched normal persons for comparison. ST segment depression occurred in all patients during exercise and persisted for 42.1 s (range 18 to 75) into the recovery period. Immediate postexercise echocardiography was started within 20.1 +/- 5.4 s and completed in 54.1 +/- 11.3 s. No patient had regional wall motion abnormalities seen on two-dimensional imaging of any myocardial segment. Thirteen patients (72%) reported reproduction of their usual chest pain, which led to termination of the test. During rapid right atrial pacing, nine patients (56%) developed ST segment depression that was associated with angina in seven. In all 16 patients, percent systolic wall thickening increased over values at rest in each myocardial segment. Percent systolic wall thickening averaged 47.1 +/- 6.1% at rest and increased to 74 +/- 8% during right atrial pacing (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939949 TI - Thallium-201 for assessment of myocardial viability: quantitative comparison of 24-hour redistribution imaging with imaging after reinjection at rest. AB - Redistribution thallium-201 imaging 2 to 4 h after exercise may be incomplete and therefore may be inadequate to fully assess myocardial variability. Late redistribution imaging 24 h after exercise has been proposed to overcome this limitation of thallium stress imaging. However, because of poor count density the image quality on these studies is often suboptimal. In the present study the diagnostic information on 24-h planar thallium redistribution images was compared with that on images obtained after a reinjection of thallium at rest. Eighty-four patients with a stress thallium-201 defect had delayed redistribution imaging after 2 to 4 h and 24 h later, and again after an injection of thallium at rest. Defect reversibility on 24-h redistribution images was compared quantitatively with that on images after injection of thallium at rest. The quality of thallium images at rest was consistently better than that of 24-h redistribution images. Poor quality studies occurred in 13% of 24-h redistribution images compared with 0.4% of the studies at rest. Significantly more defect reversibility was detected on images after the reinjection at rest. Of 41 patients who appeared to have a fixed defect at 2- to 4-h redistribution imaging, 11 (27%) had a reversible defect by 24-h redistribution imaging compared with 29 (71%) after thallium-201 reinjection. No clinical variables at the time of stress testing were predictive of late defect reversibility. It is concluded that in patients with fixed a thallium defect at 2 to 4 h after exercise, reimaging after a reinjection at rest provides better diagnostic information than does 24-h late redistribution imaging. PMID- 1939948 TI - Dobutamine thallium myocardial perfusion tomography. AB - Dobutamine has favorable properties for the pharmacologic manipulation of myocardial oxygen demand in the provocation of ischemia during the investigation of coronary artery disease. The value of dobutamine infusion for thallium myocardial perfusion tomography was assessed in 50 patients with exertional chest pain undergoing coronary arteriography. Dobutamine was infused in 5-min stages at incremental rates from 5 to 20 micrograms/kg per min or until limited by symptoms. The myocardium was divided into nine segments for analysis of perfusion. Thirty-nine of 40 patients with coronary artery disease had a reversible perfusion defect demonstrated by dobutamine thallium tomography (sensitivity 97%) and 8 of 10 patients with normal coronary arteries had normal myocardial perfusion (specificity 80%). These values were significantly better than the sensitivity and specificity of exercise electrocardiography (78% and 44%, respectively; p less than 0.01). There was a significant relation between the mean number of segments with abnormal perfusion and the number of diseased coronary vessels (0.6, 2.6, 4.4 and 6 segments in zero-, one-, two- and three vessel disease, respectively; p less than 0.001). There was also a significant relation between the maximal tolerated dose of dobutamine and the treadmill exercise time (r = 0.56, p less than 0.001), but a wide range of exercise times was achieved in the 15- and 20-micrograms/kg per min groups, principally because of exercise limitation by noncardiac symptoms. Dobutamine infusion was well tolerated in all patients, including six with asthma. There were no significant arrhythmias or limiting symptoms other than chest pain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939950 TI - Heart rate adjustment of the time-voltage ST segment integral: identification of coronary disease and relation to standard and heart rate-adjusted ST segment depression criteria. AB - To assess the effect of heart rate adjustment of the magnitude of the ST integral (ST-HR integral) on exercise test performance, the exercise electrocardiogram (ECG) of 50 clinically normal subjects and 100 patients with known or suspected coronary artery disease was analyzed. At matched specificity of 96% with standard ECG criteria (greater than or equal to 0.1 mV of additional horizontal or downsloping ST segment depression), an unadjusted ST integral partition of 16 microV-s identified coronary disease in the 100 patients with known or suspected disease with a sensitivity of only 41%, a value significantly lower than the 59% sensitivity of standard ECG criteria (p less than 0.01) and the 65% sensitivity of an ST depression partition of 130 microV (p less than 0.001). However, test performance of the ST integral was greatly improved by simple heart rate adjustment: at a matched specificity of 96%, an ST-HR integral partition of 0.154 microV-s/beat per min identified coronary disease in the 100 patients with a sensitivity of 90%, a value significantly greater than the 59% sensitivity of standard criteria and 65% sensitivity of ST depression criteria (each p less than 0.001) and similar to the 91% sensitivity of the ST-HR index and 93% sensitivity of the ST-HR slope (each p = NS). Comparison of receiver-operating characteristic curves confirmed the superior overall test performance of the ST-HR integral relative to the ST integral and ST segment depression, and demonstrated improved performance that was comparable with that of the ST-HR index and the ST-HR slope.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939951 TI - Patterns of normal transvalvular regurgitation in mechanical valve prostheses. AB - The magnitude and spatial distribution of normal leakage through mechanical prosthetic valves were studied in an in vitro model of mitral regurgitation. The effective regurgitant orifice was calculated from regurgitant rate at different transvalvular pressure differences and flow velocities. This effective orifice area was 0.6 to 2 mm2 for three tilting disc prostheses (Medtronic-Hall sizes 21, 25 and 29) and 0.2 to 1.1 mm2 for three bileaflet valves (St. Jude Medical sizes 21, 25 and 33). In the single disc valves, Doppler color flow examination disclosed a prominent central regurgitant jet around the central hole for the strut, accompanied by minor leakage along the rim of the disc (central to peripheral jet area ratio 3.3 +/- 1.2). The bileaflet prostheses showed a peculiar complex pattern: in planes parallel to the two disc axes, convergent peripherally arising jets were visualized, whereas in orthogonal planes several diverging jets were seen. Mounting the disc and bileaflet valves on a water filled tube allowed reproduction and interpretation of this pattern: for the bileaflet valve, the jets originated predominantly from valve ring protrusions that contained the axis hinge points and created a converging V pattern in planes parallel to the leaflets and a diverging V pattern in orthogonal planes. Similar patterns were observed during transesophageal echocardiography in 20 patients with a normally functioning St. Jude prosthesis. In 10 patients with a Medtronic Hall valve, a dominant central jet was observed with one or more smaller peripheral jets. The median central to peripheral jet area ratio was 5 to 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939952 TI - Doppler evaluation of aortic valve area in children with aortic stenosis. AB - To evaluate the usefulness of the Doppler-derived aortic valve area calculated from the continuity equation in assessing the hemodynamic severity of aortic valve stenosis in infants and children, two-dimensional and Doppler echocardiographic examinations were performed on 42 patients (aged 1 day to 24 years) a median of 1 day before or after cardiac catheterization. The left ventricular outflow tract diameter was measured from the parasternal long-axis view at the base of the aortic cusps from inner edge to inner edge in early systole. The flow velocities proximal to the aortic valve were measured from the apical view with use of pulsed Doppler echocardiography; the jet velocities were recorded from the apical, right parasternal and suprasternal views by using continuous wave Doppler echocardiography. The velocity-time integral, mean velocity and peak velocity were measured by tracing the Doppler waveforms along their outermost margins. Seventeen patients (all less than or equal to 6 years old) had a very small left ventricular outflow tract diameter (less than or equal to 1.4 cm) and cross-sectional area (less than or equal to 1.5 cm2). The Doppler aortic valve area calculated with use of velocity-time integrals in the continuity equation (0.57 +/- 0.25 cm2/m2, mean value +/- SD) correlated well with the Doppler aortic valve area calculated by using mean (0.55 +/- 0.25 cm2/m2) and peak (0.54 +/- 0.24 cm2/m2) velocities, with correlations of r = 0.97 and 0.95, respectively. Thirty-four patients had sufficient catheterization data to calculate aortic valve area from the Gorlin formula.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939953 TI - Transesophageal echocardiographic monitoring of interventional cardiac catheterization in children. AB - Transesophageal echocardiography was used prospectively in 22 children scheduled for interventional cardiac catheterization (9 with pulmonary valvuloplasty, 5 with aortic valvuloplasty, 1 with pulmonary angioplasty, 2 with aortic angioplasty, 2 with patent ductus arteriosus occlusion and 3 with Mustard baffle dilation) to determine its potential value as a monitoring technique. The patients ranged in age from 0.9 to 14.6 years (mean 5.4) and in weight from 9.5 to 49.2 kg (mean 21.1). Studies were completed in all patients without complications. Preintervention studies provided important new information in two patients, leading to cancellation of the planned procedure. Major contributions of transesophageal monitoring included 1) a real time assessment of catheter placement across either atrioventricular valve and the aortic valve during balloon valvuloplasty; 2) immediate assessment of aortic valve and aortic wall morphology during balloon dilation; and 3) detailed morphologic and hemodynamic information together with enhanced catheter guidance during Mustard baffle dilation. After pulmonary valvuloplasty, partial chordal rupture of the tricuspid valve was documented in one patient. In two patients, balloon catheter position was modified according to the transesophageal findings. The assessment of changes in pulmonary valve morphology and transcatheter occlusion of a patent ductus arteriosus was not enhanced by single-plane transesophageal monitoring. Pulsed wave Doppler studies contributed additional information in the assessment of immediate hemodynamic changes after interventional procedures. Transesophageal echocardiography is a new important guiding and monitoring technique during interventional cardiac catheterization procedures in children. It can provide additional real time imaging information, immediate identification of complications and assessment of hemodynamic changes. PMID- 1939954 TI - Advances in transesophageal echocardiography: impact of a changing technology on children with congenital heart disease. PMID- 1939955 TI - Recanalization of chronically occluded aortocoronary saphenous vein bypass grafts by extended infusion of urokinase: initial results and short-term clinical follow up. AB - Chronic occlusion of saphenous vein aortocoronary bypass grafts is a common problem. Although percutaneous transluminal angioplasty of a saphenous vein with a stenotic lesion is feasible, angioplasty alone of a totally occluded vein graft yields uniformly poor results. Patients with such occlusion are often subjected to repeat aortocoronary bypass surgery. Experience with a new technique that allows angioplasty to be performed in a totally occluded saphenous vein bypass graft is reported. This technique utilizes infusion of prolonged low dose urokinase directly into the proximal portion of the occluded graft. Forty-six consecutive patients with 47 totally occluded grafts were studied. Patients had undergone end to side saphenous vein bypass grafting 1 to 13 (mean 7) years previously. All patients presented with new or worsening angina pectoris with ST T changes or non-Q wave acute myocardial infarction and all had a totally occluded saphenous vein bypass graft. The new technique entailed the positioning of an angiographic catheter into the stub of the occluded graft and the advancement of an infusion wire into the graft. Patients were returned to the coronary care unit, where urokinase was delivered at a dose of 100,000 to 250,000 U/h. The total dose of urokinase ranged from 0.7 to 9.8 million U over 7.5 to 77 h (mean 31). After therapy, recanalization was seen in 37 (79%) of the 47 grafts. In 20 successfully treated patients, angiography was performed 1 to 24 (mean 11) months after treatment; 13 (65%) of these grafts were patent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939956 TI - Coronary aneurysms after stent placement: a suggestion of altered vessel wall healing in the presence of anti-inflammatory agents. AB - Coronary aneurysms are rare after conventional angioplasty and have not been reported after coronary stenting. Coronary artery stent sites were examined by follow-up angiography at a median of 4 months in 29 patients who received the Cook stent (Gianturco-Roubin) for acute coronary closure. Nineteen patients were treated with glucocorticoids administered intravenously or orally, or both, with or without colchicine and results were compared with those in 10 patients who were treated with neither agent. Standard therapy for all patients included routine administration of aspirin and heparin before and warfarin sodium (Coumadin) and aspirin after stent placement. Most patients also received dipyridamole and lovastatin during the follow-up period. Compliance with medications was confirmed by telephone conversation with each patient. Six (32%) of the 19 stented arteries showed evidence of coronary artery aneurysm, defined as expansion of the lumen outside the margins of the stent. None of the patients in the control group (who did not receive steroids or colchicine) developed aneurysm. This pattern of altered vascular healing in stented coronary segments appears to be due to the addition of multiple anti-inflammatory drugs rather than to stent presence alone. This observation demonstrates the possibility of medical impairment of normal vascular remodeling after acute injury and stent placement, which may be of benefit in designing future trials on restenosis. PMID- 1939958 TI - Inhibition of platelet function in vivo or in vitro by organic nitrates. PMID- 1939957 TI - The antiplatelet effects of organic nitrates and related nitroso compounds in vitro and in vivo and their relevance to cardiovascular disorders. AB - Organic nitrates, cornerstones of antianginal therapy, are believed to exert their principal anti-ischemic benefit by relaxing vascular smooth muscle. Recent evidence suggests that these compounds and related nitro(so) vasodilators are also potent platelet inhibitors. In view of the well recognized role of thrombotic events mediated by platelets in acute coronary syndromes, the antiplatelet effect of nitrates may also be of mechanistic importance in the treatment of these disorders. This review details the biochemical mechanism by which nitro(so) compounds inhibit platelet function and summarizes the in vitro and in vivo evidence that supports their antithrombotic effects. PMID- 1939960 TI - Augmentation of plasminogen activator inhibitor type 1 activity in plasma by thrombosis and by thrombolysis. AB - Both activation of platelets and elevation of plasminogen activator inhibitor type 1 (PAI-1) activity in plasma have been associated with acute myocardial infarction. Growth factors from platelet alpha-granules have been shown to increase PAI-1 synthesis in liver and endothelial cells in culture. The present study was designed to determine whether activation of platelets in vivo increases PAI-1 activity in plasma, thereby potentially attenuating thrombolysis. Carotid arteries in rabbits were stimulated with transluminal anodal current to initiate thrombosis manifested initially by cyclic flow variations known to reflect platelet activation. Flow was monitored with Doppler flow probes. Plasma PAI-1 activity (mean +/- SEM) assayed spectrophotometrically increased from 6.8 +/- 0.8 arbitrary units (AU)/ml to a peak of 19.1 +/- 2.9 AU/ml (n = 15) 4.8 +/- 0.6 h after the onset of cyclic flow variations. The magnitude of peak PAI-1 values correlated closely with the frequency and duration of antecedent cyclic flow variations. Complete thrombotic occlusion did not elevate PAI-1 beyond that seen with severe, repetitive partial occlusions (18.7 +/- 4.6 vs. 19.6 +/- 3.8 AU/ml). However, when recanalization of completely occluded vessels was induced with tissue-type plasminogen activator (t-PA), plasma PAI-1 increased more markedly (from 5.6 +/- 0.7 to 112.8 +/- 22.3 AU/ml, n = 11), exceeding the increase after corresponding intervals in animals in which t-PA failed to induce recanalization (from 5.2 +/- 1.1 to 28.3 +/- 6.1 AU/ml, n = 6). Thus, activation of platelets accompanying thrombosis or thrombolysis, or both, markedly increases PAI-1 activity in plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939959 TI - Clinical and pathologic manifestations of pulmonary vascular disease in the toxic oil syndrome. AB - The toxic oil syndrome in Spain affected greater than 20,000 people. In the initial stages, it was characterized by a respiratory distress syndrome with myalgias and eosinophilia. Pulmonary hypertension developed in 20% of the patients and in many, it has spontaneously regressed. Nevertheless, in a small subgroup, it has progressed to a malignant course of cor pulmonale, leading rapidly to death. Clinical and pathologic features of 40 patients with severe pulmonary hypertension due to the toxic oil syndrome are presented (32 female and 8 male patients; mean age 26 +/- 13 years). The study began in June 1981, which was near the onset of the toxic oil epidemic, and ended in December 1987, greater than 6 years later. The pulmonary hypertension is clinically and pathologically indistinguishable from primary pulmonary hypertension. Direct endothelial injury by the toxic agent is proposed as the initial trigger of this type of pulmonary hypertension, but an interaction between the toxic agent and specific individual susceptibility is probably required in its pathogenesis. PMID- 1939961 TI - Effects of pacing rate and timing of defibrillation shock on the relation between the defibrillation threshold and the upper limit of vulnerability in open chest dogs. AB - To test the relation between the defibrillation threshold and the upper limit of vulnerability, the shock strength associated with 50% probability of successful defibrillation (DFT50) and that associated with 50% probability of reaching the upper limit of vulnerability (ULV50) were determined in 20 open chest dogs with use of the delayed up-down method, with pacing drive cycle lengths of 150 to 500 ms and either single 6-ms shocks (10 dogs) or 12-ms biphasic shocks (10 dogs) given at the mid-upslope, peak and mid-downslope of the T wave of electrocardiographic lead II. The shocks were given by means of a patch-patch configuration on the anterior and posterior surfaces of the heart, which was paced from a stimulating electrode attached to the left ventricular apex. Analysis of variance showed no statistically significant differences in ULV50 as determined with different pacing cycle lengths. For monophasic shocks, DFT50 (331 +/- 66 V or 5.8 +/- 2.7 J) was not significantly different from ULV50 determined at the mid-upslope of the T wave (318 +/- 64 V or 5 +/- 2 J). The correlation coefficients between the two values were 0.74 (p = 0.014) for voltage and 0.67 (p = 0.034) for energy. In contrast, DFT50 was significantly higher than ULV50 as determined at the peak of the T wave (219 +/- 43 V or 2.3 +/- 1 J) and mid downslope of the T wave (200 +/- 38 V or 1.9 +/- 0.9 J). In three dogs, ventricular fibrillation could not be induced at the mid-downslope of the T wave with any baseline pacing (Si) cycle length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939962 TI - Right atrial ischemia exacerbates hemodynamic compromise associated with experimental right ventricular dysfunction. AB - To determine the importance of right atrial function with acute right ventricular dysfunction, sequential right ventricular and right atrial ischemia were induced in 15 dogs. Right ventricular ischemia resulted in right ventricular free wall dyskinesia, right ventricular dilation by ultrasound, elevated right ventricular filling pressure and paradoxic septal motion. There were decrements in right ventricular systolic pressure (28.9 +/- 5.5 to 25.5 +/- 4.6 mm Hg) (p less than 0.05 for these and all subsequent values) and stroke work (5.66 +/- 0.94 to 2.66 +/- 0.62 g.m/m2), resulting in reductions in left ventricular preload, systolic pressure (123 +/- 11 to 97 +/- 12 mm Hg) and stroke volume (24.2 +/- 4.3 to 19.1 +/- 5.2 ml). Right atrial contractility was augmented, as indicated by increases in peak A wave amplitude (ratio of peak A wave to mean right atrial pressure 1.22 +/- 0.02 to 1.46 +/- 0.3) and right atrial stroke work (0.11 +/- 0.02 to 0.25 +/- 0.05 g.m/m2). Right atrial ischemia depressed right atrial contraction, as indicated by decreased A wave amplitude (ratio of peak A wave to mean right atrial pressure 1.46 +/- 0.3 to 1.04 +/- 0.2) and stroke work (0.25 +/- 0.05 to 0.04 +/- 0.01 g.m/m2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1939963 TI - Thrombolysis: the need for a critical review. AB - The (Thrombolysis in Myocardial Infarction) TIMI-I trial led to the hypothesis that the greater reperfusion rate seen with recombinant tissue-type plasminogen activator (rt-PA) versus streptokinase would result in greater reductions in infarct size and mortality in patients with acute myocardial infarction. Despite extensive investigation, no trial comparing rt-PA with streptokinase (European Cooperative Study Group, Plasminogen Activator Italian Multicenter Study [PAIMS], Gruppo Italiano per lo Studio della Sopravvivenze nell'Infarto Miocardico [GISSI 2], International Study on Infarct Survival [ISIS-3], even TIMI-I itself) nor rt PA and anisoylated plasminogen-streptokinase activator complex (APSAC or anistreplase) (Bassand, TEAM-3, ISIS-3), have confirmed this hypothesis. In a reversal of traditional scientific method, the studies, rather than the unconfirmed hypothesis, have been rejected. A lack of independent review of this subject may have contributed to this outcome. It is proposed that standards of review and editorial comment mandating true critical distance and independence be followed, permitting greater independence of scientific inquiry, review and debate. PMID- 1939964 TI - Creation of the recombinant tissue plasminogen activator (rt-PA) image and its influence on practice habits. AB - American physicians have commonly practiced thrombolytic therapy for acute myocardial infarction with the recombinant form of tissue plasminogen activator (rt-PA), although its cost is much higher than that of streptokinase. The greater popularity of rt-PA is based on the belief that it is a more effective and a safer drug for achieving myocardial salvage and mortality reduction. However, a series of studies testing this assumption have not substantiated its greater efficacy or safety with respect to not only streptokinase but also urokinase and anisoylated plasminogen-streptokinase activator complex (APSAC). This editorial reviews the sequence of events that led to the creation of the rt-PA image, the mistaken premises on which it was based and the questions that need to be addressed if we are to strengthen the scientific method for evaluating similar types of drugs and its influence on practice habits including the costs to the health system. PMID- 1939965 TI - The Medicare fee schedule. PMID- 1939966 TI - Subaortic obstruction after pulmonary artery banding in patients with tricuspid atresia and double-inlet left ventricle and ventriculoarterial discordance. PMID- 1939967 TI - Effectiveness and cost effectiveness of nutrition care: a critical analysis with recommendations. PMID- 1939968 TI - Phase II: recommendations from experts in health care financing. PMID- 1939969 TI - Phase III: research designs for future studies. PMID- 1939970 TI - Lipid profiles of older women. PMID- 1939972 TI - Table tents pitch nutrition tips. PMID- 1939971 TI - Ventilatory status and patient diagnosis. PMID- 1939973 TI - Many factors influence college students' eating patterns. PMID- 1939974 TI - The next rung of the ladder: achieving and expanding reimbursement for nutrition services. PMID- 1939975 TI - A brief dietary assessment to guide cholesterol reduction in low-income individuals: design and validation. AB - Low-income Americans are at greatest risk for coronary heart disease. Dietary assessment methods are needed that can efficiently and effectively guide diet counseling to reduce serum cholesterol in this population. The Dietary Risk Assessment is a brief food frequency questionnaire designed to guide an intervention program for cholesterol reduction. It can easily be administered and scored in 10 to 15 minutes by persons who are not trained in nutrition. The assessment is culturally specific for a low-income southern population, identifies positive as well as problematic dietary behaviors, is easily interpreted, and measures potential barriers to dietary change. The assessment was validated against 3 days of dietary recall data in a sample of 42 low-income individuals recruited from the waiting room of an ambulatory care clinic. A Keys score, which measures the serum-cholesterol-raising potential of the diet, was calculated for each patient from their recall data. The Keys and Dietary Risk Assessment scores were significantly correlated (r = .60, P less than .001). We conclude that the Dietary Risk Assessment can rank individuals by level of dietary atherogenic risk adequately to guide a dietary treatment program for low income patients, an underserved population with a high prevalence of diet-induced elevations in serum cholesterol. PMID- 1939977 TI - Nutrition knowledge, attitudes, and practices of older and younger elderly in rural areas. AB - Using a mailed survey, we gathered data to examine selected aspects of nutrition attitudes, knowledge, and practices of two groups of randomly selected older individuals living in rural areas. In one group respondents were 75 through 85 years old, and in the other group respondents were 60 through 70 years old. A senior nutrition survey and a shelf inventory were used to obtain information from the 698 respondents. The 60- through 70-year-old group expressed significantly more (P less than .001) positive attitudes for efficacy, intention, and outcome expectation than the older group. In addition, the younger group had a higher level (P less than .01) of knowledge about fat and salt. They also tended to make more healthful food selections in 7 of 11 categories of the shelf inventory. Our study suggests that 75- through 85-year-old individuals have different nutrition attitudes, knowledge, and practices. Nutrition education should focus on positive messages that are age appropriate, practical, and achievable. Specific topics should include information about beneficial outcomes of healthful eating behaviors. PMID- 1939976 TI - Gender differences in adults' knowledge about fat and cholesterol. AB - Cognitive learning theories suggest that an individual's prior knowledge is a major factor for determining what can be learned. The objectives of this study were to compare the organization of knowledge about fat and cholesterol in adult, middle-class men and women and changes in that knowledge after reading an educational bulletin. Forty men and 48 women participated in two semistructured interviews to assess their knowledge; half received a US Department of Agriculture bulletin on fat and cholesterol at the end of the first interview. Concept maps (two-dimensional representations of an individual's cognitive knowledge structure) were made from the interview transcripts to assess knowledge organization. Both genders had limited knowledge, scoring less than 25% of the maximum possible score at interview 1. Overall, known and not known concepts were similar in men and women; however, women had slightly more integrated knowledge and more misconceptions than men. Both groups receiving the bulletin made significant gains in knowledge at interview 2, but knowledge gains were twice as great in men as in women. Our findings indicate that practitioners need not create separate materials about fat and cholesterol for middle-class men and women. PMID- 1939978 TI - Anthropometry and health in the elderly. AB - Measurements of height, weight, skinfold thicknesses, and circumferences were obtained along with data on health practices and disease from 424 independent living elderly in the Houston area. The objectives of the study were to examine anthropometric measurements of younger (58 through 74 years) and older (75 through 100 years) elderly individuals and to assess relationships between these measurements and health behaviors and disorders. Results demonstrated differences in anthropometric indexes due to aging and sex. Individuals who considered themselves to be more active than peers or who smoked had lower values for some anthropometric variables such as body mass index and waist circumference. Those who drank alcoholic beverages had lower values for some variables than those who stated that they did not drink alcohol. Diabetes and hypertension in the younger elderly were associated with higher values of some measurements, including waist circumference and body mass index. Anthropometric measurements in the elderly varied with sex, age, health practices, and the presence of certain disorders. PMID- 1939979 TI - Inconsistent associations among anthropometric measurements in elderly Dutch men and women. AB - In a national survey of 515 apparently healthy Dutch elderly people aged 65 through 79 years, interrelationships among weight, height, weight-for-height indexes (especially the Quetelet index), body fatness (assessed by skinfold measurements), and 24-hour urinary creatinine excretion were investigated in various age groups. Body weight, body height, and 24-hour urinary creatinine excretion (absolute and per kilogram body weight) were lower in older age groups. In men the correlation coefficient between weight and body fatness was .54 for the group aged 65 through 69 years and .33 for the group aged 75 through 79 years. In women the correlation between weight and percentage of body fat varied from .52 to .70 among the age groups. In comparison with results reported for younger adults, a lower correlation between the Quetelet index and body fatness was observed (r = .49 in men, r = .64 in women). The correlation of the Quetelet index with both height and urinary creatinine excretion tended to be higher in the older age groups. We concluded that some of the associations found were inconsistent and that there may be some doubt about the adequacy of the Quetelet index as a measure of body fatness among the elderly. However, no convenient alternative weight-for-height index is presently available. Perhaps circumferences are a better option to choose for elderly people. PMID- 1939980 TI - Warning signals for malnutrition in the elderly. AB - Aging and disability are often assumed to coexist in Western society. Nevertheless, most elderly people live in noninstitutional settings. Monitoring and improving the nutritional integrity of the elderly could play a part in helping them remain healthy and independent. A community-based approach to the prevention of malnutrition in elderly people has been developed. This approach teaches warning signals for malnutrition to care providers who are in contact with elderly men and women. Care providers learn to recognize a group of circumstances (warning signals) that could have a negative impact on an elderly person's nutritional status. Examples of risk factors are given, and the interplay between risk factors and warning signals is discussed as well as their combined application. Practical steps for simple intervention are suggested. The dietitian is the nutrition educator and coordinator of this service. PMID- 1939982 TI - Individualized menu slips improve the accuracy of patient food trays. AB - We evaluated the effect of five menu slip formats on worker preference and accuracy of food trays in a simulated hospital tray line. Menu slip formats were either individualized or preprinted, and various combinations of color coding, large type, and bold print were used to code the type of diet and the menu choices to be placed on the tray. Student volunteers who had not worked in hospital foodservice were used as tray line workers to reduce the possibility of prior preference for a menu slip format. Results indicate that menu slip format significantly affects both worker preference and the accuracy of assembled food trays. Errors were significantly lower with individualized formats that identified menu selections in bold print and type of diet in either large type or colored ink. The highest error rate was found with preprinted formats. An individualized menu slip that identified menu selections and diet orders with large type and bold print received the highest worker preference rating and resulted in the most accurate tray assembly. PMID- 1939981 TI - Characteristics of older adult learners: a guide for dietetics practitioners. AB - Characteristics of older adult learners are described and related to program development, implementation, and evaluation. The framework for designing learning experiences consists of four steps: assessment of the needs of the learner; development of learning objectives and determination of content; selection and implementation of appropriate learning activities; and evaluation of the results of learning. Four major assumptions about older adult learners are discussed based on a model designed specifically for adult learners. Active involvement through self-administered questionnaires, interviews, or focus groups helps ensure that nutrition education programs are responsive to the older adult's needs. Age-related changes (ie, in senses of sight and hearing, reaction time, and memory) and psychologic and social changes (ie, loneliness, depression, illness, financial difficulties, or loss of a loved one) may occur in many older learners and need to be considered when selecting appropriate learning activities. A single approach to nutrition education is unlikely to meet the needs and preferences of all older adults. To maximize their effect as educators, dietetics practitioners need to adjust their teaching styles and program development strategies to better fit the characteristics of older adult learners. PMID- 1939983 TI - Relationship of vitamin/mineral supplementation to certain psychologic factors. PMID- 1939984 TI - Computerized nutrition program: effect on nutrient intake of senior citizens. PMID- 1939985 TI - Indoor walking program increases lean body composition in older women. PMID- 1939986 TI - Adherence to the cardiac diet: attitudes of patients after myocardial infarction. PMID- 1939987 TI - Estimating the nutrient intake of older adults: components of variation and the effect of varying the number of 24-hour dietary recalls. PMID- 1939988 TI - Position of the American Dietetic Association: the role of the registered dietitian in enteral and parenteral nutrition support. PMID- 1939989 TI - Anita L. Owen, MA, RD, receives 1991 Copher Memorial Award. PMID- 1939990 TI - Clinical and theoretical aspects of enactment. AB - Enactment as a concept can serve analytic discourse through its established meaning of an act intended strongly to influence, persuade, or force another to react. We might agree to use the term in two complementary ways: Broadly, enactment can designate all behaviors of both parties in the analytic relationship, even verbal, in consequence of the intensification of the action intent of our words created by the constraints and regressive push induced by the analytic rules and frame. Patient and analyst are vulnerable to falling back on behaviors that actualize their intentions, doing so in ways motivated by and reflecting transference hopes, fears, and compromises shaped in their developmental past. Specifically, enactment can then be defined as those regressive (defensive) interactions between the pair experienced by either as a consequence of the behavior of the other. While nominally an interpersonal perspective, this concept of enactment facilitates more balanced attention to the involvement of both parties and to the intrapsychic dynamics in both that specifically shape their interactions. A clinical vignette illustrates the analyst's contributions to enactment, especially those reflecting his reactivated conflicts and their relation to his theoretical and technical preferences. PMID- 1939991 TI - Is the Oedipus complex still the cornerstone of psychoanalysis? Three obstacles to answering the question. AB - Current controversies about the centrality of the Oedipus complex in psychoanalysis are difficult to resolve unless we address three obstacles in the way of rational examination. The first is that the Oedipus complex, Freud's "shibboleth" of psychoanalysis, is politically controversial. Second is the great difficulty in agreeing upon the definition and boundaries of the Oedipus complex, especially the necessary complexities introduced with the negative Oedipus complex, female sexuality, the nature of the preoedipal, and counteroedipal fantasies and actions. The third obstacle involves basic questions of psychoanalytic epistemology: our criteria for evidence to prove or disprove any particular proposition. I conclude that the awareness of these difficulties signifies a certain maturation in our thinking and that the complexity introduced by these obstacles can in time provide the groundwork for a set of formulations that is richer and closer to the complexities and ambiguities of the clinical situation. PMID- 1939992 TI - Patient's surface, clinical surface, and workable surface. AB - Surface is a term often used in clinical theory, which seems to have eluded a reliable definition. Freud used the term mostly to denote the analysand's consciousness. This patient's surface does not always coincide with the data the analyst can observe, i.e., the clinical surface. It is proposed that clinical surface be understood, in contrast to other psychoanalytic concepts, as the clinical evidence that does not need conjecture to be grasped cognitively. The concept of "average expectable apperception" is introduced. Workable surface is defined as those aspects of the clinical surface that lend themselves well to the exploration of unconscious dynamics or genesis. Ideas about which surfaces are optimally workable vary according to different schools of technique. The advantages of considering clinical surface the objective anchorage of psychoanalysis as a positive science and of differentiating it from patient's surface and workable surface are discussed. PMID- 1939993 TI - The analyst's self-analysis and its impact on clinical work: a comment on the sources and importance of personal insights. AB - In reviewing descriptions of self-analysis in the literature, as part of an ongoing inquiry into the nature and role of self-analysis in the life and work of the psychoanalyst, the author noted a focus on circumscribed self-analytic work, or on a method for self-analysis that did not stress its clinical relevance. Missing were descriptions of the encompassing, multi-sourced, multimotivated, interminable nature of self-analysis in the analyst's work life and personal life. In response to those findings, the author focuses on the conduct of his self-analysis over a period of several months, following an illness experienced by his mother. He attempts to convey certain qualities of his self-analysis: it goes on all the time, it is variously fueled by experiences in and outside his consulting room, and it is practiced self-consciously and with self-discipline. He also describes the ways in which his self-analysis enhances his clinical effectiveness and promotes his personal growth, and notes that all of an analyst's experiences are interconnected opportunities for personal and professional development. PMID- 1939994 TI - A patient's transference to the analyst's supervisor: effect of the setting on the analytic process. AB - A case is presented in which the patient's transference to the analyst's supervisor became evident just prior to the switch from clinic to private patient status. The patient experienced the supervisor as a restraining father figure who protected her from acting on her erotic wishes toward the analyst. Analysis of this led to the recall of previously repressed memories of sexual wishes toward her brother, and the sense of protection from these wishes that she had gotten from the presence of her father. The literature on transference involving the supervisory constellation and the training setting is reviewed, and the concepts of split and institutional transference are examined. Factors inhibiting the analysis of patients' fantasies about the analyst's status as trainee, including the presence of the supervisor and the institute, are discussed. PMID- 1939995 TI - Presentation of clinical experience. Panel report. PMID- 1939996 TI - Sadomasochism in the perversions. Panel report. PMID- 1939997 TI - Poisoning by Gyromitra esculenta--a review. AB - Gyromitra esculenta (Pers.: Fr.) Fr. and a few other mushrooms have caused severe poisonings and even deaths in humans. Clinical data are characterized primarily by vomiting and diarrhoea, followed by jaundice, convulsions and coma. Gastrointestinal disorders distinguish this poisoning. Frequent consumption can cause hepatitis and neurological diseases. The species of concern are mainly G. esculenta and G. gigas (Kromb.) Cooke (non Phill.). Nevertheless, recent advances in chromatography, biochemistry and toxicology have established that other Ascomycetes species also may prove toxic. Gyromitrin (acetaldehyde methylformylhydrazone, G) and its homologues are toxic compounds that convert in vivo into N-methyl-N-formylhydrazine (MFH), and then into N-methylhydrazine (MH). The toxicity of these chemicals, which are chiefly hepatotoxic and even carcinogenic, has been established through in vivo and in vitro experiments using animals, cell cultures and biochemical systems. When we consider the chemical nature and the reactivity of these natural compounds, we suggest that chemical and biochemical mechanisms may explain their intrinsic biological activity. PMID- 1939998 TI - Altered developmental toxicity caused by three carrier solvents. AB - Many aquatic bioassays rely on chemical solvents to solubilize water-insoluble test materials. Interactions between solvents and test materials can lead to false positive or negative results. For this reason, tests for interactions between solvents and test materials were performed. The Frog Embryo Teratogenesis Assay--Xenopus (FETAX) was chosen because of its capacity to assess three different endpoints; mortality, malformation and embryo growth. Three solvents- dimethylsulfoxide (DMSO), acetone and triethylene glycol (TG)--were tested with two teratogens--methylmercury chloride (MMC) and trichloroethylene (TCE). DMSO potentiated the lethal effect of both teratogens but did not alter significantly the rate of malformation. Acetone increased the mortality for both teratogens, but only increased the MMC malformation greater than the additive effects. TG only increased the mortality and malformation with TCE. There were additive effects for growth for all solvents with the teratogens. The carrier solvents caused interactions even at their no-observable-effect concentration (NOEC). Therefore, the choice of carrier solvent should be made with caution. This study shows that different results can occur depending on the solvent used, and that a difference in one endpoint does not necessarily change the other endpoints. PMID- 1939999 TI - Possible involvement of 1,2-diacetylbenzene in diethylbenzene-induced neuropathy in rats. AB - The role of 1,2-diacetylbenzene (1,2-DAB) in the peripheral nerve toxicity of 1,2 diethylbenzene (1,2-DEB) was investigated in rats. Gas chromatography-mass spectrometry identified 1,2-DAB in the urine samples of rats given 165 mg kg-1 1,2-DEB orally on four consecutive days. 1,2-DAB shared not only the ability of 1,2-DEB to cause bluish discoloration of skin, internal organs and urine, but unlike 1,2-DEB it turned hair blue at the site of intraperitoneal injection. Intraperitoneal administration of 10 mg kg-1 and 20 mg kg-1 1,2-DAB to groups of 12 rats, 4 days a week for 11 and 6 weeks, caused a dose- and time-dependent decrease in mean sensory and motor conduction velocities. Recovery in a 5-week post-exposure period was gradual but consistent. The effect of 1,2-DAB on the amplitude of the sensory action potential was ambiguous. The findings support the hypothesis that the formation of 1,2-diacetylbenzene derivatives contributes to the neurotoxicity of 1,2-DEB. PMID- 1940000 TI - Organophosphate poisoning in urban zimbabwe. AB - A total of 606 organophosphate poisoning admission incidents were recorded and analysed retrospectively at the six central hospitals of Zimbabwe. The incidents covered a period of 10 years, i.e. from 1980 to 1989, inclusively. This accounted for 12% of all poisoning admission cases recorded at these hospitals and 84% of all pesticide poisoning cases. Of these organophosphate poisoning cases, 75% (450) were suicides and or parasuicides, 21% (126) were accidental, 2% (12) were homicides and 5% (30) were cases of an undetermined nature. The mortality rate was established at 8% (48). The study revealed that the 21-30-year-old age group is significantly more prone to poisoning (42% of the total) than other age groups. The mean period of hospitalization of an organophosphate-poisoned patient was found to be 8 days (the range was 1-29 days). The mean cost of keeping a poisoned patient in hospital during that period was calculated at Z$450.00 (i.e. US$225), excluding the cost of treatment. The total number of hospitalization days was 1599 and the total cost of keeping the patients in hospital was therefore Z$89,943,75, i.e. Z$11,242,96 per year. The most popular (utilized) first-line treatment (22% of all patients) was a combination of ipecacuanha syrup plus atropine, with atropine alone a poor second (10% of treated patients). PMID- 1940001 TI - Influence of age and time of administration of dithiocarbamate analogues on cadmium retention in rats. AB - In the present study the influence of age and time of chelation therapy on cadmium retention in 6-, 11-and 14-day-old rats and in 6-week-old rats has been investigated. Chelating agents N-benzyl-dithiocarboxy-D-glucamine (BDCG), sodium N-(metho-xybenzyl)-D-glucamine dithiocarbamate monohydrate (MeOBDCG) and N-methyl N-dithiocarboxy-D-glucamine (MDCG) were administered intraperitoneally to three different groups at a dose of 1 mmol kg-1 body weight on two occasions following 115mCd intraperitoneal administration; immediately and after 24 h; after 24 h and 48 h; or after 48 h and 72 h. The 115mCd retention in the whole body and organs was determined 6 days after cadmium administration. Chelation therapy very effectively reduced cadmium retention in the whole body and organs, MeOBDCG being the most effective. The effects of chelating agents were significantly more pronounced in older than younger animals and in the case of early rather than late administration. The highest fraction of cadmium administered was retained in the liver, where also the strongest effect of chelation therapy was observed. Mobilized cadmium was excreted almost exclusively by the faecal route. PMID- 1940003 TI - Interaction of ethanol and xylene in their effects on erythrocytes and other haematological parameters in the rat. AB - Rats were given ethanol in drinking water for 8 months, followed by inhalation exposure (5 h daily) to 12,000 mg m-3 xylene for 9 days. Combined exposure to xylene and ethanol induced the same changes in the haematological, biochemical and biophysical parameters of the erythrocyte membrane as those found previously in our experiment with toluene-ethanol. Macrocytosis, a decrease in sedimentation rate and erythrocyte packing difference, as well as decreased fluidity of the erythrocytes membrane in the middle zone of the lipid bilayer, were the most significant changes of exposure to ethanol and xylene. PMID- 1940002 TI - Ni3S2 uptake by lung cells and its interaction with plasma membranes. AB - The uptake and biological transformation of Ni3S2 was studied on guinea pig alveolar macrophages (GPAM) in primary culture. Two different pathways are observed: (i) phagocytosis of alpha Ni3S2 crystals and subsequent degradation to minute particles, which are recovered bound to the membranes of phagocytic vacuoles and to lysosomal membranes. These degradation products contain sulphur in very reduced quantities, as revealed by energy-dispersive spectrometry (EDS). (ii) Extracellular degradation to regular round particles (0.1-0.2 microns) and irregular minute particles (10-30 nm). Round particles may enter the cell by pinocytosis and are characterized by the loss of sulphur. Minute particles are bound preferentially to cell membranes, to cytoplasmic organelles, such as endoplasmic reticulum, mitochondria and peroxysomes, to liposomes and to the euchromatinic part of nuclei. EDS analyses in these particles revealed the substitution of sulphur by phosphorus. This observation suggests the formation of an Ni-P complex with the phosphate groups of membranous and liposomal phospholipids and of the euchromatinic part of DNA or RNA. Steady-state fluorescence polarization analysis were carried out on GPAM and, for comparative purposes, on human embryonic pulmonary epithelial cells (L132 cell line). In both cell types they revealed a significant increase of membrane fluidity, induced either by desaturation of aliphatic chains or directly by the cleavage of fatty acid chains. PMID- 1940005 TI - Four-week inhalation exposures of rats to aerosols of three lubricant base oils. AB - Sprague-Dawley rats were exposed to aerosols of one of three base stocks used to formulate lubricating oils. These stocks were a solvent-refined oil (SRO), a hydrotreated and acid-washed white oil (WTO) and a severely hydrotreated and hydrocracked oil (HBO). Exposures were for 6 h per day, 5 days per week for ca. 4 weeks. There were four groups of rats for each study (10 per sex per group). Aerosol concentrations were ca. 0, 50, 210 and 1000 mg m-3 for each material; the mass median aerodynamic diameter was ca. 1 microns. Following the last exposure, all animals were sacrificed and necropsied. Samples were taken for serum chemistry, hematology, sperm morphology, weights of seven organs and histopathology on at least nine organs. Body weights and clinical signs were not affected by exposures. The only treatment-related changes were in the lung and associated lymph nodes. Both the wet weight of the lung and the dry/wet weight ratio increased in a concentration-related manner. Associated with the increased weight were accumulations of foamy alveolar macrophages, particularly in alveoli close to alveolar ducts. Mild infiltration by neutrophils was observed with WTO and SRO; thickened alveolar walls were noted with the highest concentration of HBO. These mild responses to exposures at very high concentrations indicate a low degree of toxicity for these aerosols. PMID- 1940004 TI - Effects of soman on calcium uptake in microsomes and mitochondria from rabbit aorta. AB - Daily administration of soman for several days results in several alterations in the vascular neuroeffector system. To determine whether or not soman alters intracellular Ca2+ uptake, the effects of acute exposure to soman or 7-day administration of 5 micrograms kg-1 of soman on the capacity of microsomes and mitochondria from rabbit aortic vascular smooth muscle to take up 45Ca2+ were determined. Acute exposure to soman concentrations of 1-100 microM did not alter significantly (P greater than 0.05) 45Ca2+ uptake by either microsomes or mitochondria. On the other hand, 7-day soman administration markedly reduced (P less than 0.05) 45Ca2+ uptake by both microsomes and mitochondria. Thus, calcium uptake and intracellular calcium uptake-dependent responses will be affected by repeated soman administration. PMID- 1940006 TI - Physico-chemical properties of amphoteric, isoelectric, macroreticulate buffers. AB - We report here the properties of a new family of resins possessing an amphoteric character and able to strongly buffer at their pI values. They have been adopted as carriers for growth of cells in tissue culture and for hydroponics (Righetti et al. 1991; J. Biotechnol. 17, 169-176) but it is to be expected that such resins could have interesting chromatographic applications. It has been found that such beads [made by incorporating a pK 6.2 weak acrylamido base and a pK 4.6 weak acrylamido acid in a 2:1 ratio (thus with a pI of 6.2) into a neutral polyacrylamide backbone], independently from their initial conditioning (acid- or base-washed), spontaneously seek their equilibrium position (pI value) upon washing off excess titrant. Thus, upon potentiometric titration, they are seen to buffer in both directions of the pH scale (contrary to the behaviour of a pure carboxyl or a pure amino surface, which will exhibit only unidirectional buffering power). From the behaviour of these amphoteric beads when polymerized in the absence or in the presence of salts (0.2 M NaCl), it is hypothesized that, for exerting buffering power, both the buffering ion and its counterion must be incorporated non-randomly in the chain, but as a couple or in close proximity. Upon random incorporation of the two ions, buffering power is lost. PMID- 1940007 TI - Turbidity as a measure of particulate subcellular fraction yield. AB - Turbidity measurement, as an estimate of the concentration of a particulate subcellular membrane fraction, is an effective alternative to protein assay. As exemplified by purified myelin membrane the technique is fast, accurate, and consumes no sample, giving it certain advantages over protein assay in some applications. PMID- 1940008 TI - Studies of the effect on tumor and normal cells in vitro with bioactive materials isolated from algae by a microcalorimetric method. AB - Recently much attention has been focused on the human physiological actions with bioactive materials from algae to enhance immunocompetence and to strengthen antineoplastic activity. In the study reported in this paper an MS 80 standard Calvet microcalorimeter was used for measuring the thermogram of HeLa, human breast carcinoma (Bcap-37) and diploid fibroblasts from human feral lung (2BS) under conditions with or without the presence of bioactive materials (Sp) from algae. At the same time, the cell number was counted, the inhibition rate of growth and the death rate were obtained. It has been shown that the Sp (100 micrograms/ml) was the growth inhibitor and lethal to tumor cells (Bcap-37 and HeLa), but had no influence on the normal (2BS) cells under the same conditions in vitro. PMID- 1940009 TI - Evaluation of the reticuloendothelial system function by the vascular clearance of chondroitin sulfate iron colloid. AB - Vascular clearance of chondroitin sulfate iron colloid (CSFe) was evaluated as a test for the reticuloendothelial system (RES) in rabbits. Injected CS59Fe was taken up by the RES in the liver (49%) and bone marrow (41%) after 60 min, suggesting its application for the RES function test. The clearance rate (K value) of CSFe from the blood was calculated by measuring serum Fe concentrations after releasing iron from CSFe at certain intervals after injection. Depending upon different injected doses, K-values were varied and the phagocytic velocity, computed by multiplying K-values by corresponding injected doses, reached a plateau at high doses, indicating the phagocytosis of CSFe by the RES takes a saturation process. Double-reciprocal plotting of the dose and the phagocytic velocity showed a linear relationship, which provided the data on the maximum phagocytic velocity (Vmax), 0.122 mg/kg/min, and the CSFe concentration producing 1/2 Vmax (Kp), 0.426 mg/kg. Thus, this CSFe clearance test can be used for the evaluation of the RES function. PMID- 1940010 TI - Thermogenesis of white adipocytes: a novel method allowing long-term microcalorimetric investigations. AB - A microcalorimetric method was developed to facilitate long-term assessment of energy balance in isolated fat cells. White rat adipocytes were primary cultured in glass ampoules with a matrix of agar-gel. Heat production was measured continuously over 3 days with an LKB BioActivityMonitor. In order to assist interpretation of the microcalorimetric measurements, glucose consumption and lactate and pyruvate production were determined in parallel cultures. Heat production, glucose consumption and lactate production were in an apparent steady state throughout the study whether employing aerobic (94 pW, 0.50 and 0.44 pmol/cell. h, respectively) or partial anaerobic experimental conditions (39 pW, 0.41 and 0.57 pmol/cell.h, respectively). However, oxygen availability influenced the apparent heat production and glucose and lactate metabolism. With partial anaerobiosis a 59% lower heat production, an 18% lower glucose consumption and a 30% higher lactate production than by employing aerobic experimental conditions were observed. PMID- 1940011 TI - Innovative developments in isotachophoresis (displacement electrophoresis). AB - This Mini Review is aimed at characterizing the innovative developments in isotachophoresis (ITP) during the past few years, discussing in turn new theoretical, analytical, preparative and applicative aspects of this unique separation method. Examples given from our laboratory include the study of the detailed dynamics of the ITP separation of four components by computer simulation and experimental validation in a capillary-type instrument with multiple sensors along the separation trough; the anionic ITP analysis in presence of a strong cathodic electroosmotic flow using an open-tubular fused-silica capillary with on column multiwavelength detection, and the fractionation of proteins in a screen segmented, rotating column as well as by recycling ITP. PMID- 1940012 TI - In memoriam: Chandler McCuskey Brooks. PMID- 1940013 TI - Peripheral arterial chemoreceptors and hypertension. AB - Functional studies in humans and animals with essential hypertension have shown a hyperventilation under resting conditions and striking respiratory and circulatory reactions to hypoxic and hyperoxic tests. There is some evidence that these reactions are due to enhanced activity of the peripheral arterial chemoreceptors. In contrast, in secondary (renal) hypertension such findings could not be observed. Many morphological, morphometrical and biochemical studies have been performed on the carotid bodies of a variety of hypertensive patients and animal models. Whilst their structure and catecholamine content are changed in hypertension, there are many differences in different types of hypertension and, furthermore, a convincing link between the morphological and biochemical findings from the carotid body studies and their functional overactivity has not been shown. Some of these alterations are caused by the elevated blood pressure (e.g. vascular pathology); others are the expression of general disturbances in the hypertensive disease state (e.g. differences in catecholamine content) whilst others are probably of genetic origin but independent of elevated blood pressure (carotid body volume in different rat models of hypertension). This paper reviews the findings on carotid body structure and function in a variety of animal models of hypertension and in primary and secondary human hypertension. PMID- 1940015 TI - Lesions of the amygdaloid central nucleus block conditioned cardiac arrhythmias in the rabbit receiving digitalis. AB - We have previously reported [15] that malignant cardiac arrhythmias can be evoked in the rabbit receiving digitalis by cardiovascular changes in response to (a) a Pavlovian aversively conditioned stimulus (CS) or (b) electrical stimulation of the amygdaloid central nucleus (ACE), a structure which contributes to Pavlovian conditioned cardiovascular responses in the rabbit. The present study was designed to examine further the role of the ACE in arrhythmogenesis by determining the effect of lesions of the ACE on the occurrence of CS-evoked arrhythmias during digitalis administration in the rabbit. Two groups of rabbits (ACE lesion and SHAM) received electrodes implanted bilaterally in the ACE, while a third group (UNOP) served as an unoperated control. All rabbits were given Pavlovian conditioning trials in which a tone conditioned stimulus (CS) was paired with an eyelid shock as an unconditioned stimulus (US). Twenty-four h later, rabbits in the lesion group received bilateral lesions of the ACE. Twenty four h after the lesion, rabbits in all three groups were given a retention test in which an i.v. infusion of ouabain was delivered, followed by 20 CS alone trials. Presence or absence of arrhythmias was scored during the pre-CS baseline and CS periods for each trial. All three groups exhibited few instances of pre-CS baseline arrhythmias, the frequency of which did not differ between groups. The SHAM and UNOP control groups exhibited a significant increase in the occurrence of CS-arrhythmias compared to pre-CS levels. This increase was blocked in the group receiving lesions of the ACE, as was CS-induced bradycardia which typically occurs in response to the CS in the rabbit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940016 TI - Epicardial distribution of ST segment and T wave changes produced by stimulation of intrathoracic ganglia or cardiopulmonary nerves in dogs. AB - Sixty-three ventricular epicardial electrograms were recorded simultaneously in 8 atropinized dogs during stimulation of acutely decentralized intrathoracic autonomic ganglia or cardiopulmonary nerves. Three variables were measured: (1) isochronal maps representing the epicardial activation sequence, (2) maps depicting changes in areas under the QRS complex and T wave (regional inhomogeneity of repolarization), and (3) local and total QT intervals. Neural stimulations did not alter the activation sequence but induced changes in the magnitude and polarity of the ST segments and T waves as well as in QRST areas. Stimulation of the same neural structure in different dogs induced electrical changes with different amplitudes and in different regions of the ventricles, except for the ventral lateral cardiopulmonary nerve which usually affected the dorsal wall of the left ventricle. Greatest changes occurred when the right recurrent, left intermediate medial, left caudal pole, left ventral lateral cardiopulmonary nerves and stellate ganglia were stimulated. Local QT durations either decreased or did not change, whereas total QT duration as measured using a root-mean-square signal did not change, indicating the regional nature of repolarization changes. Taken together, these data indicate that intrathoracic efferent sympathetic neurons can induce regional inhomogeneity of repolarization without prolonging the total QT interval. PMID- 1940014 TI - Regional extraction of circulating norepinephrine, DOPA, and dihydroxyphenylglycol in humans. AB - Dihydroxyphenylglycol (DHPG) is the main intraneuronal metabolite of the sympathetic neurotransmitter, norepinephrine (NE), and dihydroxyphenylalanine (DOPA) the immediate product of the rate-limiting step in catecholamine biosynthesis. Simultaneous measurements of regional rates of appearance (spillovers) of NE, DOPA, and DHPG in plasma have the potential to provide unique information about aspects of sympathoneural function but have not actually been measured in humans. In the present study, spillovers of DHPG, DOPA, and NE in the heart, head, leg, and lungs, were estimated from regional extraction fractions of infused [3H]-1-NE, DHPG, and [13C6]DOPA or unlabelled DOPA in humans during cardiac catheterization. There was little cardiac extraction of DHPG (7 +/- SEM 2%) or DOPA (8 +/- 4%) but substantial extraction of NE (69 +/- 4%). Values for cardiac spillover of DHPG and DOPA therefore were similar to values for the arteriovenous increment times plasma flow (arteriovenous production rate), whereas the cardiac spillover of NE averaged about 7-times the NE arteriovenous production rate. Cardiac DHPG spillover (28 +/- 3 ng/min) exceeded the spillovers of NE (9 +/- 2 ng/min) and DOPA (15 +/- 4 ng/min). In contrast, cranial DOPA spillover (159 ng/min) exceeded those of NE and DHPG by 8- and 2-fold and accounted for about 1/10 of the total spillover of DOPA into arterial plasma. In the femoral vascular bed, arteriovenous production rates of NE and DHPG were unrelated to femoral spillovers of NE and DHPG. Arterial and regional clearances of [13C6]DOPA were similar to those of unlabelled DOPA. The results suggest that (1) endogenous NE, DOPA, and DHPG all are released into the bloodstream by the heart, head, and limbs of humans; (2) DHPG and DOPA are not co-released with NE; (3) cardiac arteriovenous production rates of DOPA and DHPG can be used to indicate cardiac spillover of these catechols, whereas the cardiac NE arteriovenous production rate substantially underestimates cardiac NE spillover; and (4) estimates of limb spillover of NE and DHPG require concurrent measurements of the corresponding regional clearances. PMID- 1940017 TI - The sympathoexcitatory response following selective activation of a spinal cholinergic system in anesthetized rats. AB - This study was performed to help elucidate the role of spinal cholinergic neurons in cardiorespiratory function by selective activation of spinal or medullary cholinergic systems in anesthetized rats. A selective site of action of cholinergic drugs on the spinal cord was obtained by refining the method of intrathecal (i.t.) drug injection to localize drug distribution to specific spinal segments. I.t. injection of the cholinesterase (ChE) inhibitor, neostigmine (NEO), produced a significant reduction in spinal, but not medullary tissue levels of ChE, and evoked marked pressor and tachycardic responses without any changes in respiratory parameters. In contrast to i.t. injection, intracisternal (i.c.) injection of NEO which inhibited both spinal and medullary ChE, produced characteristic respiratory changes--increased tidal volume and decreased respiratory rate and minute volume, as well as pressor and tachycardic responses. I.t. injection of the muscarinic antagonist, methylatropine, inhibited the cardiovascular responses to i.t. NEO, but not the cardiorespiratory responses to i.c. NEO. These cardiovascular responses to i.t. NEO were blocked by spinal transection, but not by midcollicular transection. Finally, the pressor and tachycardic responses to i.t. NEO were inhibited following peripheral alpha adrenergic and beta-adrenergic blockade, respectively. These results indicate that activation of the spinal cholinergic system selectively produces a sympathoexcitatory response through spinal muscarinic receptor activation independent of respiratory changes. This finding is consistent with the possibility that such responses are elicited by activation of a non-cholinergic bulbo-spinal sympathoexcitatory pathway at the spinal level, or at higher centers through an ascending pathway. In either case, the spinal cholinergic system appears to be anatomically and pharmacologically distinct from the medullary pathway and may subserve a different function. PMID- 1940018 TI - Interactions between reflexes evoked by distension and mucosal stimulation: electrophysiological studies of guinea-pig ileum. AB - Intracellular recording methods were used to examine stereotyped reflexes evoked in the circular muscle of guinea-pig small intestine by distension or repetitive deformation of the mucosal villi, in vitro. Both stimuli evoked compound excitatory junction potentials (EJPs) on the oral side of the site of stimulation and compound inhibitory junction potentials (IJPs) on the anal side. Stimulation of the mucosa by application of 10 microliters of 0.5 M HCl evoked similar reflex responses in the circular muscle. The compound EJPs evoked by mucosal stimulation were depressed, but not abolished, by 1 microM hyoscine, indicating that these responses were partially mediated by release of acetylcholine, as are the equivalent responses evoked by distension. The compound EJPs and the compound IJPs evoked by maintained distension or by repeated mechanical stimulation of the mucosa were transient, lasting in most cases for 3-5 s before the membrane potential returned to resting level. This decline (rundown) occurred in part of the circuit close to the site of stimulation as stimuli applied elsewhere during the period of rundown evoked normal EJPs and IJPs. Mechanical stimuli (brush strokes that deformed the mucosal villi) applied to the mucosa at the site of a maintained distension evoked responses of normal amplitude during the period when the response to the distension had declined to zero. In contrast, during the period when the responses to repetitive mechanical stimulation of the mucosa had disappeared, the reflex responses evoked by distension at the same site were substantially augmented. Chemical stimulation of the mucosa with acid also enhanced the responses to distension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940019 TI - Acrylamide-induced autonomic neuropathy of rat mesenteric vessels: histological and pharmacological studies. AB - The effects of chronic acrylamide treatment on the autonomic nervous system were investigated by histochemical and pharmacological studies. Histochemical studies showed that acrylamide caused different degrees of damage to different nerve fibre types: calcitonin gene-related peptide (CGRP)-immunoreactive (IR) nerves showed the greatest reduction in intensity and number; noradrenaline (NA) containing nerves were somewhat less affected; substance P (SP)-IR nerves were reduced in number, but this was not significant. The profiles of SP- and particularly of CGRP-IR nerves from treated animals were noticeably different to those from the control group, being flattened and irregular. Periarterial nerve stimulation (4-32 Hz) of the isolated rat mesenteric arterial bed preparation at basal tone elicited frequency-dependent vasoconstrictor responses. The magnitude of these responses was significantly reduced at higher frequencies in acrylamide treated animals. In preparations with tone raised by the addition of methoxamine (10(-5) M), and in the presence of guanethidine (5 x 10(-6) M), periarterial nerve stimulation elicited vasodilator responses. These responses, which result from stimulation of sensory nerves, were greatly reduced in acrylamide-treated animals. There was a tendency for mesenteric beds from acrylamide-treated animals to show increased vasoconstrictor responses to doses of exogenous NA, although this was not significant. Responses to exogenous adenosine 5'-triphosphate (a cotransmitter with NA from sympathetic nerves) were not affected. In the raised tone preparation, vasodilator responses to exogenous CGRP (the principal vasodilator sensory transmitter of rat mesenteric arteries) were not affected by acrylamide treatment. Hence, it is unlikely that the reduced responses to nerve stimulation were due to defects in the postjunctional receptors for the principal transmitters of sympathetic and sensory-motor nerves. There was no difference in the ability of mesenteric beds from control and treated animals to vasodilate in response to acetylcholine or sodium nitroprusside, or to vasoconstrict in response to potassium chloride, indicating normal smooth muscle and endothelial responses. These results suggest that chronic acrylamide treatment produces peripheral autonomic neuropathy of rat mesenteric vessels, manifested as a dysfunction of sympathetic and sensory-motor nerves. Furthermore, the graded destruction of nerve types, such that damage occurred in the order: CGRP-IR greater than NA greater than SP-IR, indicated a differential sensitivity of different nerves to this toxin. PMID- 1940020 TI - Changes in brain glucose retention produced by the stimulation of an insulin sensitive reflexogenic zone in rats. AB - Although it has been reported that insulin decreases glucose efflux from the brain causing an increase in brain glucose retention, its mechanism of action is still unknown. The present results indicate that peripheral insulin may act through the stimulation of insulin-sensitive receptors localized in the region irrigated by the coeliac trunk and innervated by the vagus nerve. Stimulation of this zone in anaesthetized, artificially ventilated rats with a bolus millidose of insulin (50 mU) caused a significant increase in brain glucose retention as a result of decreased glucose efflux from the brain. The same dose of insulin injected 1-2 cm caudally in the abdominal aorta below the coeliac trunk failed to increase brain glucose retention. The effects of insulin above the coeliac trunk disappear when the vagus nerve is sectioned, suggesting that the vagus participates as the afferent pathway of this reflex. PMID- 1940021 TI - Effects of depleting central and peripheral adrenaline stores on blood pressure in stroke-prone spontaneously hypertensive rats. AB - The potential role of adrenaline, both circulating and in the central nervous system, in the maintenance of high blood pressure was examined in stroke-prone spontaneously hypertensive rats (SHRSP). alpha-Monofluoromethyldopa, a long lasting inhibitor of dopa decarboxylase, was used to induce rapid depletion of central and peripheral catecholamine stores. Subsequent inhibition of phenylethanolamine-N-methyltransferase (PNMT) allowed the gradual restoration of dopamine and noradrenaline but not adrenaline, resulting in a greater relative depletion of adrenaline. Adrenaline was almost totally depleted in the circulation and peripheral tissues. The resting level of blood pressure, however, was unaffected, excepting after administration of a vasopressin (AVP) antagonist. Moreover, there was no reduction in the magnitude of acute pressor responses to electrical stimulation of the rostral ventrolateral medulla oblongata (C1 area), despite extensive loss of adrenaline from the brainstem and spinal cord. The results suggest that adrenaline contributes to the resting level of blood pressure but that its loss can be offset by the pressor activity of AVP. Thus neither central nor peripheral adrenaline stores appear to be essential for the maintenance of hypertension or for centrally-evoked vasoconstriction in adult SHRSP. PMID- 1940022 TI - Influence of higher brain centres and vasopressin on the haemodynamic response to acute central hypovolaemia in rabbits. AB - We tested whether suprapontine brain centres contribute to the sudden failure of vasoconstriction that occurs in unanaesthetized rabbits during acute reduction in central blood volume. Haemorrhage was simulated by gradually inflating a cuff around the thoracic inferior vena cava so that cardiac output fell by about 8% per min. In intact rabbits, and in rabbits that had undergone craniectomy but not decerebration, the haemodynamic response to simulated haemorrhage was always biphasic. During the first, compensatory phase, systemic vascular conductance fell almost in proportion to the fall in cardiac output so that arterial pressure fell by only about 10 mmHg. When cardiac output had fallen by about 50%, a decompensatory phase supervened in which systemic vascular conductance rose abruptly, arterial pressure fell steeply to less than 40 mmHg, and the plasma arginine vasopressin (AVP) level rose. High mesencephalic decerebration did not affect the compensatory phase, but it abolished the decompensatory phase and there was no rise in the plasma AVP level. The decompensatory phase was not restored by intravenous administration of AVP. We came to two conclusions as a result of this study. Suprapontine brain centres do not influence the arterial baroreflex-mediated vasoconstriction that occurs during the first phase of acute central hypovolaemia. However, the sudden failure of vasoconstriction that occurs during the second phase of acute central hypovolaemia, attributable to a signal from the heart and mediated by a delta-opioid receptor mechanism in the brainstem, does depend on the integrity of suprapontine brain centres, though not on neurohypophysial AVP release. PMID- 1940023 TI - Autonomic nervous system tests depend on resting heart rate and blood pressure. AB - In order to study the effects of baseline blood pressure and heart frequency on autonomic function tests, 75 normal subjects (aged 8-96 years) were investigated. Heart rate variability was studied at rest, during deep breathing, following standing up and during a Valsalva manoeuvre. Blood pressure changes were recorded during standing up and during sustained handgrip. Responses were described as ratios and as differences to study the efficacy of both methods. Multiple regression analysis showed that significant relationships with the resting heart rate existed for ratios but not for differences. The blood pressure rise in the sustained handgrip test showed a significant relationship with resting blood pressure regardless of the description method. As expected, relationships with age existed for all four heart rate tests regardless of the description method. The blood pressure responses were not significantly related to age. We advise that heart rate test results should be presented as differences, as this avoids the need for correction for the resting heart rate. Correction for the resting blood pressure improves the accuracy of the standing up blood pressure test. Correction for age remains necessary for heart rate tests but not for blood pressure tests. PMID- 1940024 TI - Transient appearance of immunoreactivity for Ca-binding protein (spot 35 calbindin) in small principal neurons in the superior cervical ganglion of pre weanling rats. AB - Immunoreactivity for rat cerebellar calbindin, termed spot 35-calbindin, is transiently expressed largely in numerous small principal neurons of the superior cervical ganglion in pre-weanling rats and disappears by the fourth postnatal week. Preganglionic denervation results in a slower rate of disappearance of the immunoreactivity in ganglion neurons. This finding suggests that small principal neurons in the superior cervical ganglion may exert some yet to be determined Ca mediated functions that are not shared with larger neurons at the pre-weanling stage. PMID- 1940025 TI - Assessment of the neural control of the circulation during psychological stress. AB - In this study, we used spectral analysis of short-term R-R and systolic arterial pressure (SAP) variabilities to estimate the changes in neural control of the circulation produced by psychological stress. The 0.1 Hz low-frequency (LF) component of R-R and SAP variabilities provided a quantitative index of the sympathetic activity controlling heart rate and vasomotion. Conversely the high frequency (HF) respiratory component of R-R variability provided an index of vagal tone. In conscious dogs we used the seemingly stressful situation of being accompanied for the first time to the experimental laboratory as a stimulus. In human subjects we used mental arithmetic. In both cases LF of R-R and SAP variabilities increased significantly suggesting enhanced sympathetic activity both to the SA node and the vasculature. In man, the index alpha, a measure of the overall gain of baroreceptor mechanisms, was found to be reduced during mental arithmetic. Spectral analysis of cardiovascular variabilities thus suggests that in man and in conscious dogs psychological challenges induce a profound re-arrangement of neural control of the circulation, which appears to be characterised by sympathetic predominance and which can be monitored by this technique. PMID- 1940026 TI - Differentiated hemodynamic responses to central versus peripheral administration of corticotropin-releasing factor in conscious rats. AB - Corticotropin-releasing factor (CRF) modifies cardiovascular function and hemodynamic status after administration into the central nervous system and into the peripheral circulation. The mechanisms by which CRF alters arterial pressure and heart rate have been examined in detail whereas little information exists regarding the processes mediating CRF-induced changes in regional blood flow. Therefore, studies were performed in conscious, unrestrained Sprague-Dawley rats to examine potential mechanisms underlying the regional hemodynamic effects of intracerebroventricular versus intravenous administration of CRF. Intracerebroventricular administration of CRF increased arterial pressure, heart rate, and mesenteric vascular resistance while decreasing iliac vascular resistance. Intravenous pretreatment with the CRF receptor antagonist, alpha helical CRF9-41, did not alter the cardiovascular and hemodynamic responses to central administration of CRF. In contrast, prior ganglionic blockade prevented CRF-induced responses except for the reduction in iliac vascular resistance. Intravenous administration of CRF reduced arterial pressure and mesenteric vascular resistance, elevated heart rate, and transiently increased iliac vascular resistance. Intravenous pretreatment with alpha-helical CRF9-41 completely abolished the cardiovascular and hemodynamic responses to peripheral administration of CRF. Ganglionic blockade prior to intravenous administration of CRF augmented the reductions in arterial blood pressure and mesenteric vascular resistance, prevented the increase in heart rate, and unmasked a decrease in iliac vascular resistance. The divergent actions and mechanisms of action of CRF on regional hemodynamics when administered peripherally, as opposed to centrally, indicate that this peptide produces different hemodynamic effects that are specific to its site of action. PMID- 1940027 TI - Secretory reflexes in ileum and jejunum: absence of remote effects. AB - We have tested the hypothesis that luminal secretagogues initiate neural reflexes that alter ion transport in small intestinal segments proximal or distal to the site of the secretory stimulus. Effects of secretagogues that act by different mechanisms were studied in vitro by measuring short circuit current (ISC) of ileum or jejunum mounted in a unique flux chamber while proximal mucosa in neural continuity with the tissue was perfused with secretagogues (Na deoxycholate. Escherichia coli STa, 5-hydroxytryptamine, theophylline) or was stimulated electrically (EFS). No proximal stimulus affected distal ISC. We also studied in vivo adjacent segments of ileum or jejunum in neural continuity but with unconnected lumens. In anesthetized rabbits, we measured transmural electrical potential difference and fluid movement (Phenol red marker). Stimulation of proximal segments of ileum or jejunum with STa, or of ileum with 5-HT or Na deoxycholate did not affect distal transport. Stimulation of distal segments of ileum and jejunum with STa or 5-HT, or of jejunum with Ha deoxycholate did not affect proximal transport. We conclude that the secretion caused by luminal secretagogues in the rabbit small intestine is limited to the area of stimulation. PMID- 1940028 TI - Disturbed metabolism of glucose and related hormones in familial amyloidotic polyneuropathy: hypersensitivities of the autonomic nervous system and therapeutic prevention. AB - Regulation of glucose metabolism was evaluated by oral glucose tolerance test (OGTT) in patients with familial amyloidotic polyneuropathy (FAP). Upon oral administration of a loading dose of glucose, plasma levels of glucose, insulin and glucagon changed abnormally in all FAP patients tested. Although plasma levels of glucose and insulin in the fasted patients were within normal ranges, 33% of FAP patients showed hypoglycemia after transient hyperinsulinemia during the examination. Furthermore, another three patients showed transient hypoglycemia during their daily life. Thus, perturbed glucose metabolism should be taken into account for treating patients with FAP. The salivary glands as well as the lacrimal glands showed transient hypersecretion after chewing a gum. Histochemical analysis at autopsy revealed significant amyloid deposition in the stroma, nerves and vessels of the pancreas, but not in Langerhans islets. Similar appearance was recognized in the salivary glands. These results suggest that denervation supersensitivity might occur not only in the exocrine glands but also in the endocrine gland. PMID- 1940029 TI - Neurotensin-like immunoreactivity in presumptive baroreceptor neurons innervating the guinea pig carotid sinus. AB - This study was carried out to determine the ultrastructure and origin of previously described neurotensin-like immunoreactive (NT-LI) nerve fibres in the wall of the carotid sinus of the guinea pig. In our degeneration experiments, these NT-LI axons were unaffected by surgical sympathectomy but disappeared in response to transection of the carotid sinus nerve, thus suggesting a sensory origin. This assumption could be supported by combined retrograde tracing and immunohistochemistry. Primary afferent neurons of the sensory glossopharyngeal (petrosal) ganglion projecting to the carotid sinus were identified by injecting the retrograde fluorescent tracer, Fluoro-Gold, into the sinus wall, and some of these neurons displayed NT-LI. Within the carotid sinus, the terminals of these NT-LI sensory neurons exhibited ultrastructural features characteristic of baroreceptor endings, i.e. axonal swellings filled with mitochondria and closely associated to elastin. However, many endings also fulfilling the ultrastructural criteria for baroreceptors were devoid of immunolabelling. Thus, we conclude that the NT-LI terminals constitute a subgroup rather than the entire population of baroreceptor endings within the guinea pig carotid sinus. With respect to the established pharmacological effects of NT in guinea pig, we propose an involvement of NT-LI fibres in the modulation of baroreception at the peripheral level. PMID- 1940030 TI - Calbindin-immunoreactive nerve terminals in the guinea pig coeliac ganglion originate from colonic nerve cells. AB - Previous work has shown that calbindin-immunoreactive (calbindin-IR) nerve terminals are numerous in guinea pig prevertebral ganglia. A high proportion of those colonic nerve cells that project to the inferior mesenteric ganglia are calbindin-IR, but none of the neurons that project from the small intestine to the coeliac ganglion are immunoreactive for calbindin. The present work was designed to determine the source of the calbindin-IR fibres and the pathways by which they reach the coeliac ganglion. Sections through the major nerve trunks that connect with the coeliac ganglion revealed numerous calbindin-IR fibres in the inferior coeliac nerves and in the intermesenteric nerves, while there were very few fibres in the splanchnic or superior coeliac nerves. When all peripheral nerve connections to a lobe of the coeliac ganglion were cut, all calbindin-IR terminals degenerated. Cutting the ileo-caeco-colic nerves caused a substantial reduction in the density of nerve fibres in the coeliac ganglion, whereas no significant reduction could be detected when the intermesenteric nerves were cut. However, lesion of both the ileo-caeco-colic and intermesenteric nerves caused all the calbindin-IR nerve fibres in the coeliac ganglion to degenerate. It is concluded that most or all of the calbindin-reactive nerve terminals in the coeliac ganglion originate from the large intestine and that most reach the ganglion via the ileo-caeco-colic nerves. Thus many colonic intestinofugal neurons, supplying both the coeliac and inferior mesenteric ganglia, are immunoreactive for calbindin, whereas small intestinal intestinofugal neurons are not immunoreactive for this protein. PMID- 1940032 TI - Hyperperfusion and enhanced metabolic state of the brain during sudden lowering of the cutaneous temperature in rats. AB - Forty-eight anesthetized and artificially ventilated rats were pretreated with the ganglion blocking agent, pentolinium (5 mg/kg, i.v.), followed by continuous phenylephrine infusion for maintenance of normotension. The rats were subjected to mock treatment (16 rats), to sudden exposure to thermoneutral water (34-36 degrees C, 16 rats), or to cold water (16 degrees C, 16 rats). The latter treatment lowered the cutaneous temperature to 25-30 degrees C. Neither one of these treatments produced any significant changes in arterial pressure or heart rate. Exposure to cold elicited hyperperfusion (microsphere method) in each of the brain regions studied. The increase in cerebral cortical blood flow (by 59 +/ 8%, mean +/- SEM) was most significant. The cerebral cortical metabolic rate for oxygen was increased by 46 +/- 10%. During the cold exposure, excellent tight coupling between the metabolic rate and blood flow was observed in the cerebral cortex. Mock treatment and exposure to thermoneutral water resulted in only trivial increases in blood flow and in metabolic rate. Thus, during cold exposure, an enhanced metabolic state of the brain represented the primary determinant increasing the brain blood flow, provided that normotension was maintained. PMID- 1940031 TI - Hyperperfusion of the rat brain during reflex hypertension induced by sudden lowering of the cutaneous temperature. AB - In anesthetized and artificially ventilated rats, passive or reflex hypertension was produced by ligation of the abdominal aorta (12 rats), or sudden lowering of the cutaneous temperature to 25-30 degrees C achieved by exposure to cold water (26 rats), respectively. Cold exposure increased the blood flow (microsphere method) in all of the brain regions studied by 54-174% in the face of a reflex increment in the arterial pressure by 40% on average. The vascular resistance was changed by 0-(-)32%. Such hemodynamic alterations were greater in almost all of the brain regions than would be anticipated from the autoregulatory function of the brain circulation, as evidenced by a comparison with those observed during passive hypertension. Exposure to thermoneutral water resulted in the minimal changes in the hemodynamic states of the systemic as well as brain circulations (5 rats). The sympathetic nerves innervating the cranial vessels were strongly activated during the cold exposure, as confirmed by the observation of a large increase in flow in the temporalis muscle after acute surgical sympathectomy. However, sympathetic denervation did not alter the degree of hemodynamic changes occurring in the brain regions during cold exposure. We conclude that, in the face of reflex hypertension induced by cold exposure, the powerfully activated sympathetic nerves failed to exert their well-known effect on the brain blood flow which prevents it from rising to an excessively high level. PMID- 1940033 TI - Bunionectomy with metatarsal osteotomy. PMID- 1940034 TI - Calcaneal "L" osteotomy: a retrospective study. AB - In this retrospective study of 36 patients and 58 feet, the "L" shaped osteotomy of the calcaneus body was investigated. The procedure, designed to add intrinsic stability to the shape of the osteotomy, was performed to correct triplane deformities of the heel in a variety of pathologic foot types. A retrospective analysis of clinical and radiographic data suggests that this procedure is a valuable alternative for surgical treatment of deformities of the calcaneus. Advantages appear to be predictability, stability, and versatility with respect to triplane reduction of deformities. A reliable method of evaluating calcaneal position both perioperatively and intraoperatively is also presented. PMID- 1940035 TI - Retrospective statistical analysis of factors influencing the formation of long term complications following hallux abducto valgus surgery. AB - A retrospective analysis was performed to determine the long-term results of hallux abducto valgus surgery done under the auspices of the Texas Health Science Center at San Antonio and its teaching hospitals. Two hundred eighty-five patients with a postoperative follow-up ranging from 3 to 10 years were studied. Attempts were made to study many of the patient demographic factors and perioperative procedures that acted to affect the development of a long-term complication. It was found that type of procedure, past medical history, age, medical control, and location of the surgical suite were all important variables to consider in this regard. PMID- 1940036 TI - Ganglions in the sinus tarsi. AB - The contents of the sinus tarsi are reviewed along with an analysis of ganglions. The possibility of ganglions as a cause of sinus tarsi syndrome is supported by the case reports. The formation of ganglions in the sinus tarsi and their role in the etiology for this condition are emphasized. PMID- 1940038 TI - Infected granuloma and inclusion cyst secondary to a retained foreign body. AB - Foreign body granuloma formation and epidermal inclusion cyst formation are a common result of retained foreign bodies. The subsequent rupture of an inclusion cyst will result in abscess formation along with ulceration. The following is a review of pathology involved in granuloma formation, as well as a presentation of an interesting case involving granuloma formation secondary to a retained foreign body. PMID- 1940037 TI - Characteristics and operative management of supination external rotation ankle fractures. AB - Identification and management of the acutely fractured ankle is discussed by the authors. The Lauge Hansen classification system, and in particular, supination external rotation injuries, is evaluated. Intraoperative technique, perioperative considerations, and generalized management of these pathologic conditions are reviewed, according to the authors' experiences. PMID- 1940039 TI - Postoperative evaluation of Keller's arthroplasty and arthrodesis of the first metatarsophalangeal joint using the EMED gait analysis system. AB - The authors examined 10 patients who had arthrodesis at the first metatarsophalangeal joint and 10 patients who had Keller's arthroplasty operation. The EMED gait analysis was used to measure the pressure distribution over the sole of the foot during walking. Arthrodesis group had significantly increased maximum pressure in the first and third metatarsal regions. The Keller arthroplasty group had the lowest maximum pressure in the big toe but it was not significant. PMID- 1940040 TI - The triplane Austin bunionectomy: a review and retrospective analysis. AB - The purpose of this manuscript is to introduce an alternative method of performing triplane Austin bunionectomies using a 0.062-inch Kirschner wire for fixation. This procedure was employed in clinical situations where there was an elevated first ray and/or a submetatarsal two lesion intractable plantar keratoma. X-ray criteria include a mild to moderate increase in the intermetatarsal angle (IMA) and a proximal articular set angle (PASA) deformity. Elevatus of the first ray is evident. Thirty-six cases were reviewed over a 5 year period. Follow-up ranged from 6 months to 3 years. Statistical results support the use of this capital osteotomy for the reduction of intermetatarsal angle and proximal articular set angle, and to plantarflex the first ray. Early mobilization with return of function of first metatarsophalangeal joint (MPJ) range of motion makes this an ideal procedure for the podiatric surgical patient who needs to return to activity as soon as possible. PMID- 1940041 TI - Calcaneonavicular bar resection: a retrospective study. AB - Fourteen patients (16 feet) were reviewed an average of 4.5 years after undergoing treatment by calcaneonavicular bar resection. After subjective and objective evaluation, 75% (12 feet) were judged to have had satisfactory results. Preoperative degenerative changes in the rearfoot correlated directly with poor results. Recurrence of the bar in every case was associated with inadequate resection. The study showed no difference in the results when resecting completely ossified bars as compared with resecting incompletely ossified bars. PMID- 1940042 TI - Spontaneous Achilles tendon rupture in a patient with systemic lupus erythematosus. AB - Spontaneous rupture of the Achilles tendon, which is associated with underlying systemic disease and concurrent oral corticosteroid therapy, is a relatively rare occurrence, with very few cases reported in the English medical literature to date. Patients with this affliction frequently present weeks to months after the rupture occurs because there is no succinct traumatic event. The neglected rupture renders surgical repair more difficult secondary to the retraction of the triceps surae muscle group and the concomitant increase in width of the defect that results. The authors present a case report of a patient with a neglected spontaneous rupture of the Achilles tendon who had been on oral corticosteroid therapy to treat the manifestations of systemic lupus erythematosus. A gastrocnemius recession was performed in a "V to Y" fashion to gain needed lengthening, and an end-to-end anastomosis was also performed. The plantaris tendon was then used to help reinforce the anastomosed site. PMID- 1940043 TI - Organizing thromboembolus in the plantar venous arch. AB - The authors present a case report of a symptomatic organizing thromboembolus in the plantar venous arch. Surgical intervention is curative. A review of the literature as it pertains to venous thrombogenesis is presented. PMID- 1940044 TI - Macrodactylia fibrolipomatosis of the foot. AB - Macrodactylia fibrolipomatosis is a rare congenital anomaly or neonatal form of enlargement of the digits. An infant with this malady affecting the left foot is described by the author. Initial observation, followed by appropriate surgical intervention, consisted of amputation and debulking procedures. Improved functional and cosmetic appearance is the desired result. PMID- 1940045 TI - Plantaris tendon reconstruction of the lateral ankle ligaments. AB - Numerous procedures have evolved to operatively stabilize the ankle suffering from chronic inversion instability. The use of the plantaris tendon to anatomically reconstruct the lateral collateral ankle ligaments is among those that avoid the complication of restriction of subtalar joint range of motion. The authors present a modified technique of reconstructing the calcaneofibular and anterior talofibular ligaments using a plantaris tendon that maintains its insertion. A retrospective study of eight patients that elected the procedure for chronic ankle instability was conducted. The average follow-up was 12.7 months. Significant improvement in functional score (p less than 0.01) and talar tilt (p less than 0.05) was noted following the procedure. No restriction of subtalar joint motion was observed in any patient after the procedure. The advantages and disadvantages of the procedure are discussed. The authors conclude that the procedure appears to be a desirable alternative in achieving ankle stability while maintaining normal hindfoot function. PMID- 1940046 TI - The Keller arthroplasty with use of the Dow Corning titanium hemi-implant. AB - Complications following the Keller arthroplasty, such as instability, shortening, and recurrence, are well known. Implants acting as a joint spacer may present some of these complications. Presently, silicone is the implant material most widely accepted and used, despite its unsuitability for long-term use and potential to produce bone and soft tissue pathology. Titanium is a more suitable material for long-term implantation and has been available since 1986 for use in the first metatarsophalangeal joint. Presented is a brief review of first metatarsophalangeal arthroplasty progressing to the development of the Titanium hemi-implant and a case report of its use with a 3-year followup. PMID- 1940047 TI - Diseases of the foot: test of radiographic interpretation. AB - The authors present a variety of radiographic pathologies affecting the foot and ankle. Some of these are intrinsic to the body part, while others reflect more systemic etiologies. Queries are initially posed, answers provided, and then justification of the correct response afforded. PMID- 1940048 TI - Amphotericin B selectively stimulates macrophages from high responder mouse strains. AB - Lymphoid cells from most inbred mouse strains respond to amphotericin B (AmB) induced immunostimulation. However, C57BL/6 mice and related strains display low or absent lymphoid cell stimulation by AmB and enhanced susceptibility to AmB toxicity. Experiments reported here show that in vitro incubation with AmB can stimulate AKR (AmB-high responder strain) macrophage proliferation. Intraperitoneal injection of AKR mice with AmB also elicits a population of macrophages primed for enhanced oxidative burst activity after triggering by zymosan particles. Under the same experimental conditions, AmB elicits a population of very weakly responsive macrophages from C57BL/6 mice. The low responsiveness of C57BL/6 macrophages correlates with previous observations that AmB is a potent immunoadjuvant and B cell mitogen in most inbred strains, but it selectively lacks immunoadjuvant effects in C57BL/6 mice and it also fails to induce polyclonal B cell stimulation in their spleen cell suspensions. Similarly, in measurements of protein synthesis in vitro, high concentrations of AmB produce a greater inhibition of protein synthesis in C57BL/6 peritoneal macrophages than in parallel cultures of AKR macrophages. These findings support the hypothesis that the macrophage is an important target cell in the mediation of AmB-induced immunomodulation. PMID- 1940049 TI - Cytokine inhibition by a novel steroid, mometasone furoate. AB - Mometasone furoate (9 alpha, 21 dichloro-11 beta, 17 alpha dihydroxy-16 alpha methyl-1,4 pregnadiene-3, 20 dione-17-[2'] furoate) was an unexpectedly potent inhibitor of the in vitro production of three inflammatory cytokines, IL-1(1), IL 6, and TNF-alpha. The potency of mometasone furoate in inhibiting cytokine production was compared to that of hydrocortisone, betamethasone, dexamethasone, and beclomethasone. IL-6 and TNF-alpha were both produced by WEHI-265.1 (murine myelomonocytic leukemia) cells following stimulation by lipopolysaccharide (LPS). Twenty-four hours after stimulation by LPS, the cell-free supernatant fluids were removed. Their cytokine content was analyzed using ELISAs specific for each cytokine. IL-1 synthesis was induced in the harvested peritoneal macrophages of BALB/c mice by incubation with LPS for twenty-four hours. The IL-1 content in the cell-free supernatant fluids was determined by the thymocyte-costimulator bioassay. Using these systems, mometasone furoate was found to be the most potent steroid tested for inhibiting the production of the three cytokines. The IC50's were 0.05 nM (IL-1), 0.15 nM (IL-6), and 0.25 nM (TNF-alpha). The inhibition of the production of proinflammatory mediators by extremely low concentrations of mometasone furoate suggests that this steroid should be highly effective in various disorders. PMID- 1940051 TI - Mitogen induced proliferative responses of lymphocytes from spot (Leiostomus xanthurus) exposed to polycyclic aromatic hydrocarbon contaminated environments. AB - The marine fish spot, Leiostomus xanthurus, was collected from five sites in the lower Chesapeake Bay system representing a gradient of sediment polycyclic aromatic hydrocarbon (PAH) concentrations. The proliferative responses to mitogens by anterior kidney lymphocytes were assessed using [3H]-thymidine uptake by replicating DNA. The data shows two different mitogen-dependent lymphocytic responses as the sediment PAH levels increase at the sampling sites; a suppression of the response to the T cell mitogens, concanavalin A (Con A) and phytohemagglutinin, and a sharp augmentation of the response to B cell mitogen, lipopolysaccharide (LPS), as well as to poke weed mitogen and peanut agglutinin. The magnitude of the lymphoproliferative responses correlated strongly with the total sediment PAH concentrations (r2 greater than 0.8). A similar correlation was also observed with 15 selected individual PAH compounds regardless of their molecular weights. By maintaining the fish in clean York River water for up to 24 weeks, it was possible to reverse the augmented proliferative responses to LPS of fish from all sampling sites and to increase the reduced responses to Con A, in fish from three sites, and partially in two sites where sediments were highly contaminated with PAH. These results suggest that the proliferative responses of fish lymphocytes to mitogens may be a potentially sensitive biomarker of exposure to, and effects of xenobiotics. PMID- 1940050 TI - Influence of arecoline on immune system: II. Suppression of thymus-dependent immune responses and parameter of non-specific resistance after short-term exposure. AB - Arecoline, a major alkaloid of arecanut was screened to explore its modulatory influence on cell-mediated immune response in a murine model system. The in vivo and in vitro effects were evaluated at subtoxic concentrations of arecoline. Delayed type hypersensitivity (DTH) reactions to sheep red blood cells (SRBC) were evaluated in male mice. When treated subcutaneously with 20 mg/kg bw (1/5 of LD50) dose of arecoline for 1, 2 or 3 weeks, the DTH reactions were significantly suppressed. At arecoline concentration of 10 mg/kg bw, there was a moderate reduction in DTH response, while no appreciable change was observed at a dosage of 5 mg/kg bw. The effects were not dependent on the duration of treatment. In contrast, treating with arecoline continuously for 4 days following SRBC immunization showed significant suppression in DTH reactions at both 10 and 20 mg/kg bw doses. When treated after 12 h following immunization with 20 mg/kg bw arecoline, significant reduction in DTH reactions were seen. While moderate reduction in response was observed with arecoline dosage of 10 mg/kg bw, there was no alteration in response at the dose level of 5mg/kg bw. Recovery experiments in mice revealed that arecoline mediated effects are of a reversible nature. Arecoline treatment did not appreciably alter the host resistance to endotoxin shock. In vitro experiments revealed both dose-dependent and time dependent cytotoxic effects of arecoline when spleen cells were incubated with varying concentrations of arecoline. Concomitant exposure of arecoline at concentrations of 10(-6) - 10(-4) M with con A, markedly suppressed both 3H thymidine incorporation and interleukin-2 production of splenic cells. In contrast, concomitant exposure of arecoline with IL-2 did not alter 3H-thymidine incorporation in the IL-2 dependent cytolytic T-lymphocyte line (CTLL), except at the concentration of 10(-4) M arecoline. From these studies it is concluded that the dose-dependent suppressive effects of arecoline on DTH response to SRBC and on certain in vitro lymphocyte functions are more clear than the host resistance to endotoxin shock. PMID- 1940052 TI - Membrane depolarization was required to induce DNA synthesis in murine macrophage cell line PU5-1.8. AB - The role of membrane potential (Em) on the initiation of DNA synthesis in murine macrophage cell line PU5-1.8 was investigated with fluorescent probes bis-oxonol and diS-C3-(5). Incubation of PU5-1.8 cells in high K(+)-HEPES buffer or with gramicidin at 37 degrees C for 1h that depolarized the membrane induced [3H] thymidine incorporation and expression of early response gene such as c-myc and c fos. When PU5-1.8 cells were treated with a number of agents including fetal calf serum (FCS), lipopolysaccharide (LPS), epidermal growth factor (EGF), N-formyl methionyl-leucyl-phenylalanine (FMLP) and bradykinin (BK), only FCS caused DNA synthesis and membrane depolarization. Other agents had no effect on these events. The FCS-mediated DNA synthesis in PU5-1.8 cells was inhibited by clamping the membrane potential with valinomycin. Moreover, intracellular alkalinization induced by nigericin at pH 7.9, which is believed to be a permissive signal for mitogenesis, caused membrane depolarization. On the other hand, challenge of cells with phorbol 12-myristate 13 acetate (PMA) suppressed the K(+)-mediated DNA synthesis. However, the treatment of cells with PMA did not change the membrane potential but suppressed the gramicidin-mediated membrane depolarization. These observations suggest that there is a correlation between membrane depolarization and initiation of DNA synthesis in PU5-1.8 cells. PKC may be acting as a modulator in this transducing pathway. PMID- 1940053 TI - Immuno-enhancing effects of ricin. AB - The effect of ricin on human peripheral blood mononuclear cells (PBMC) was tested in vitro. At low concentrations (10(-3) and 10(-4) micrograms/ml), ricin potentiated the effect of lipopolysaccharide to induce interleukin 1 (IL-1). Ricin was not mitogenic or co-mitogenic with phytohaemagglutinin or concanavalin A in PBMC cultures at low concentrations (less than 10(-4) micrograms/ml). Higher concentrations of ricin (greater than 10(-3) micrograms/ml) inhibited production of IL-1 by PBMC and the mitogen-driven proliferation of PBMC cultures. PMID- 1940054 TI - The dose-dependent influence of mechloretamine on the response to sheep erythrocytes in mice. Comparison of immunostimulating properties of mechloretamine with levamisole. AB - The effect of the following doses of mechloretamine: 1, 5, 10, 25, 50, 100, 250 and 500 micrograms/kg on the immunological response in mice immunized with sheep red blood cells (SRBC) was investigated. The number of plaque forming cells (PFC) to SRBC, the serum hemagglutinins level and the number of lymphocytes forming E or EAC-rosettes were determined. Depending on mechloretamine dose the following effects on the tested parameters were obtained: (i) only stimulating--1 and 5 micrograms/kg, (ii) stimulating or suppressive according to the test--10-100 micrograms/kg, (iii) only suppressive--250 and 500 micrograms/kg. Mechloretamine (5 micrograms/kg) induced the increase in PFC in comparison with levamisole (2 mg/kg). The difference between the action of mechloretamine and levamisole used in immunostimulating doses on the increased anti-SRBC antibodies or on the E rosette forming lymphocytes was revealed. PMID- 1940055 TI - Enhanced macrophage anti-microbial activity following dimethylnitrosamine exposure in vivo is related to augmented production of reactive oxygen metabolites. AB - Previous results demonstrated that mice exposed in vivo to DMN were more resistant to both bacterial and tumor challenges. Furthermore, macrophages (M phi) isolated from these animals demonstrated increased functional properties. As reactive oxygen intermediates (ROI) represent a key mechanism of anti-microbial action, it was important to determine whether ROI levels in M phi were related to augmented anti-microbial action in animals exposed to DMN in vivo. Peritoneal exudate M phi elicited with either thioglycollate (TG), Con A or C. parvum (CP) were examined for the production of ROIs. TG-M phi, Con A-M phi and CP-M phi obtained from animals exposed to DMN showed increased superoxide anion (O2-) production in vitro following stimulation with either phorbol myristate acetate (PMA) or opsonized zymosan (Op-zym) when compared to vehicle M phi. ROI production by bone marrow-derived macrophages (BMDM) produced by either GM-CSF or CSF-1 was also determined. BMDM from DMN-exposed animals obtained using either growth factor, had increased ROI production at 3, 5, 7 and 9 d of culture compared to vehicle BMDM. There was no shift in the kinetics of ROI production during differentiation of these BMDM. Analysis of extracellular anti-listericidal activity of TG- and CA-elicited M phi demonstrated that only TG-M phi obtained from DMN-exposed animals had enhanced killing capacity. There were no differences in intracellular anti-microbial activity in TG- and CA-elicited M phi obtained from either vehicle or DMN-exposed animals. TG-elicited M phi from either vehicle or DMN-exposed animals were examined for anti-microbial activity and H2O2 production following in vitro exposure to PMA. M phi from both vehicle and DMN treatment groups had enhanced killing and H2O2 production following PMA treatment, while PMA-stimulated TG-M phi from DMN-exposed animals demonstrated significantly higher levels of H2O2 production and cell killing as compared to all other treatment groups. These results suggest that previously observed increases in anti-microbial action by M phi from DMN-exposed animals are due in part to enhanced ROI production. PMID- 1940056 TI - A study on the B cell activity in protein deficient rats exposed to methyl isocyanate vapour. AB - The effect of MIC on the humoral immunity of the malnourished (protein deficient) subjects has been investigated. A single exposure of MIC (1.60 mg/l) on protein deficient rats showed no significant change in the body weight and mortality rate compared with the normal but the serum protein levels were found significantly low (P less than 0.01) in the protein deficient diet fed control (PDC) ones. Both PDC and protein deficient MIC exposed (PDMIC) rat showed diminished B-cell proliferation with the optimal dose of LPS, compared to the NDC and normal diet fed MIC exposed (NDMIC) group. Furthermore significant suppression (P less than 0.01) in the B-cell activation by LPS was observed in the PDMIC compared to PDC. The total IgM level in PDMIC was 43% less while 26% higher in NDMIC compared to NDC. The total IgG level in PDMIC and NDMIC was higher (20%) compared to NDC, while 25% less in PDC. The antigen specific B-cell immunity was affected in PDMIC, PDC and NDMIC. As the terminal differentiation process of B-cells were found equally affected in both PDC and NDMIC, it appears that MIC has no synergistic effect on the humoral immunity of the protein malnourished host. PMID- 1940057 TI - Role of levamisole as immunomodulant in mouse lymphoma model. AB - Levamisole (LMS) has been considered an immunorestorative agent capable of enhancing host's antitumor immune responses. Clinical studies showed that LMS plays a significant role in adjuvant chemotherapy of colorectal cancer. Therefore studies were performed to test whether LMS would be able to restore graft responsiveness in mice with drug-dependent, age-dependent or virus-dependent immunodeficiency. The results show that LMS has little or no influence on the limited antitumor effects of Dacarbazine or Ara-C in mice bearing allogeneic leukemias (i.e. in a host-tumor model in which immuno-chemotherapy synergism occurs with less immunodepressive anticancer drugs). Moreover LMS does not alleviate allograft response inhibition produced by high-dose Dacarbazine or by a mouse RNA virus. However the agent restored graft responsiveness in aged animals. The limited immunoenhancing effects of LMS, as detected in the present study, suggest that the clinical efficacy of the agent could be due to mechanisms not entirely related to its immunopharmacological properties. PMID- 1940058 TI - Clinical and immunologic effects of combination therapy with intravenous immunoglobulins and AZT in HIV-infected patients. AB - 30 patients with HIV infection were enrolled to evaluate the clinical efficacy and toxicity of zidovudine (AZT), 0.5 g/day p.o. (Group A) vs. AZT 0.5 g/day p.o. plus intravenous immunoglobulins (IVIG), 0.4 g/kg of body weight for three consecutive days, followed by one treatment of 0.6 g/kg of body weight every fourth week (Group B), over a period of one year. The study was open and randomized. The treatment groups were compared using the following study variables: 1) type of infections, recurrences and severity; 2) change in CD4+ T and CD8+ T cell count; 3) change in platelet count; 4) change in TNF alpha serum levels; 5) the probability of not developing an opportunistic infection over a period of 12 months. Patients from Group B developed less pathological events in comparison to Group A. No significative differences were evident with regard to values of T cell subsets obtained before and after treatment in each group and between the two groups. On the contrary, in 12 out of 15 patients from Group B there was a significant increase in platelet count. In both groups there was a significant decrease of mean serum levels of TNF alpha when a comparison was made between time 12 vs. time 6. However, when data were expressed as single values, in three subjects from Group B TNF alpha was still detectable by time 12 vs. 9 individuals in Group A. The cumulative probabilities of developing an opportunistic infection over the 12 months of treatment in the Group A subjects were significantly higher than in the Group B subjects (p less than 0.01). Adverse effects--nausea and gastric pain--were reported for 3 individuals (20%) from Group A and 4 patients (26%) from Group B. In conclusion, patients treated with AZT are especially likely to benefit from IVIG prophylaxis. PMID- 1940059 TI - Expression of estradiol and progesterone receptors by histologically normal endometria of women with postmenopausal bleeding. AB - Estradiol and progesterone receptor levels (RE2, RP) were measured in histologically normal endometria of women with postmenopausal bleeding (PMB) and the results were compared to those in histologically normal endometria of premenopausal and postmenopausal (PM) women and to those in pathological PM endometria. In histologically normal PMB endometria, RP levels were comparable to those in secretory premenopausal endometria and significantly higher than those in PM atrophic endometria. The RP levels in the former group correlated with the respective RE2 levels and the values of the ratio RP/RE2 occupied a mid-zone between those ratio values of normal premenopausal or pathological PM endometria on the one hand and normal PM endometria, on the other hand. The cytosolic/nuclear distribution of both receptor levels revealed that in both PMB and in pathological PM endometria, only a small fraction of the receptor was recovered in the nuclear extract. Expression of the RE2 and RP in the PMB and in the pathological PM endometria were associated with undetectable plasma E2 levels. These results indicate that histologically normal PMB endometria are biochemically active and suggest that endometrial growth and RE2, RP expression in PMB and pathological PM endometria are stimulated by a factor which acts distal to the RE2 acceptor. PMID- 1940060 TI - Papillary thyroid carcinoma: occurrence and types of lymph node metastases. AB - Fifty-seven (35.6%) of 160 patients with papillary thyroid carcinoma had lymph node metastases at the primary treatment. Children and adolescents were most frequently affected (69.2%), followed by the age group of 21-40-year olds (38.8%). Those older than 40 had the lowest incidence of lymph node metastases (29.6%; p less than 0.05). One fifth of all patients had lymph node metastases as first indication of papillary thyroid carcinoma. Two thirds of these patients were 40 years old or younger. Lymph node involvement affected the jugular vein in nearly all cases (78.8%) and the upper mediastinum as well in just under 15%. Women predominated (67.5 vs. 35.3%; p less than 0.05) if there was intrathyroidal tumor growth with lymph node metastases which occurred most frequently in the age group of 21-40-year olds. On the other hand, men had the highest incidence (67.7 vs. 32.5%; p less than 0.05) of lymph node metastases in connection with tumor growth outside the organ. Fixed lymph node metastases occurred more often in men, particularly in those older than 40 years of age. A pT4 stage (tumor growth outside the organ, 66.7%) was often present at the same time. Especially young patients had a high incidence of lymph node metastases in connection with multifocal intrathyroidal tumor growth, the lymph node metastases often being substantially larger than the mostly occult foci of thyroid carcinomas. Cystic degenerations were occasionally mistaken for cervical cysts. PMID- 1940061 TI - Thyroid hormones in tissues from human embryos and fetuses. AB - This study was intended to quantify T3 and T4 in various human tissues at different stages of gestation as a contribute in the evaluation of the role of thyroid hormones in fetal development, particularly before the maturation of fetal thyroid function. Moreover, for a better comprehension of the influence of thyroid hormone status in tissues, the study was extended to adults. Embryonic specimens were obtained from voluntary abortions between 6 and 12 weeks of gestation, fetal and neonatal specimens from fetuses and neonates between 15 and 36 weeks of gestation after spontaneous abortion or stillbirth, and adult specimens from men (age range: 45-65 years) after death for cardiovascular diseases. Thyroid hormones were measured by the method of Gordon and coworkers. In embryos T3 and T4 were measured in limbs, carcasses, brain and liver: considering all values measured in the period 9-12 weeks, a mean concentration of 0.11 ng/g for T3 and 1.28 ng/g for T4 was obtained. In pooled limbs of 6-8 weeks T3 was barely measurable (0.01 ng/g). In the carcasses there was an increase in T3 and T4 concentrations of 40 and 20 times respectively from the 9th to the 12th week, when thyroid follicles organization takes place. In fetuses and adults T3 and T4 were measured in brain, heart, kidney, liver, lung, skeletal muscle and skin (mean concentrations: 0.86 ng/g for T3 and 7.44 ng/g for T4 in fetuses and neonates; 1.36 ng/g for T3 and 12.75 ng/g for T4 in adults). Hormones concentration increased with gestational age; the T3/T4 ratio increased until 22 24 weeks, when the prevalent increment in T4 occurs. T3 concentration up to 30 weeks was generally higher in tissues than in cord serum of the corresponding age. During the last month of gestation T3 increment was faster in serum. T4 level was always predominant in serum. In conclusion, T3 and T4 have been detected in the limbs of embryos before the onset of thyroid hormone secretion. Concentrations were 1/150 and 1/70, of the normal maternal blood values respectively. It is conceivable that these hormones are of maternal origin, and the question of whether such small quantities may play a role in fetal development is open. PMID- 1940062 TI - The role of hyperinsulinemia in the development of lipid disturbances in nonobese and obese women with the polycystic ovary syndrome. AB - In order to establish the role of insulin in the pathogenesis of lipid abnormalities in hyperandrogenic women with the polycystic ovary syndrome (PCO) 49 women aged 18 to 35 yr with a normal glucose tolerance test were studied. They were divided into two groups: 27 women with PCO (9 obese and 18 nonobese), and 22 healthy women (12 with simple obesity and 10 with normal body weight). In the PCO group, the fasting insulin levels and the insulin response to oral glucose load were higher than in the matched controls. Significantly lower levels of HDL2 cholesterol and higher levels of apolipoprotein B were observed in obese and non nonobese PCO patients. In obese women with PCO this was associated with lower levels of HDL-cholesterol and apolipoprotein A-I (Apo A-I), whereas the levels of total triglycerides and VLDL-triglycerides (VLDL-TG) were increased. Multiple regression analysis in PCO women, after adjustment for age, body mass index and the levels of insulin and sex hormones, showed a strong positive correlation between the fasting insulin levels and total triglycerides and VLDL-TG, while a negative correlation was found between fasting insulin levels and apo A-I. These results indicate that hyperinsulinemia may play a role in the development of lipid disturbances in women with the PCO. PMID- 1940063 TI - Changes in parafollicular cells of rats neonatally treated with estradiol. AB - The parafollicular cells of male and female rats neonatally (3rd day) treated with a single dose (1 mg) of estradiol dipropionate, and sacrificed in peripubertal (38th day) or adult (80th day) period of life, were investigated. These studies included examinations of silver-stained properties of parafollicular cells, morphometric analyses of both the cells and nuclear area and ultrastructural characteristics. Estradiol treatment led to a significant increase of the cellular and nuclear area (micron 2) in both females and males. Different from intact animals remarkable degranulation and hyperplasia of parafollicular cells were evident in estradiol-treated rats. It may be concluded that this sexual hormone applied in neonatal period has an effect on parafollicular cells expressed up to adult period of life. PMID- 1940064 TI - Leydig cell tumor estrogen secretion: suppression by a gonadotropin releasing hormone agonist. AB - A 35-year-old patient and a 48-year-old patient with a benign feminizing Leydig cell tumor were treated just before orchiectomy with a GnRH agonist, respectively buserelin, administered subcutaneously for 7 days (500 micrograms/8 h) and intranasally for the following 7 days (400 micrograms/8 h), and long acting detryptoreline in a single im injection of 3.75 mg. After 10 days of treatment, breast pain was relieved. In the first patient, serum immunoassayable FSH and LH first rose and reached a peak by the first day, then decreased to nearly basal values; they unexpectedly rose again and the second peak was as high as the first one; they again decreased just before orchiectomy. The bioassayable to immunoassayable LH ratio rose and reached a peak on day 3; then it decreased and reached a nadir before orchiectomy. In the second patient, after the initial increase, FSH and LH decreased regularly with no subsequent increase. In both patients, an increase in plasma testosterone (T) and estradiol (E2) followed the first gonadotropin peak, then T and E2 decreased progressively and reached castration levels. It was thus possible to strongly inhibit both E2 tumoral secretion and T secretion. Our findings suggest that E2 tumoral secretion inhibition by GnRH agonists might be proposed as an alternative treatment to surgery, i.e. for patients who refuse orchiectomy or for whom surgery is contraindicated. PMID- 1940065 TI - Post-partum hypercalcemia in hereditary hyperphosphatasia (juvenile Paget's disease). AB - Hereditary hyperphosphatasia is a rare bone disorder characterized by increased bone turnover, elevated alkaline phosphatase (ALP) and bone deformity. We describe a patient with a mild form of hereditary hyperphosphatasia who was initially hypercalcemic in childhood with remission after puberty. Symptomatic hypercalcemia recurred during lactation after each of two pregnancies, associated with increased bone turnover (rise in ALP, osteocalcin, and urine hydroxyproline excretion) which appeared to be independent of changes in major calcium regulating hormones. The mechanism for the development of post-partum hypercalcemia remains unclear but may relate to the relative estrogen deficiency of lactation. We postulate that acute estrogen withdrawal may result in hypercalcemia in the presence of markedly increased bone turnover. PMID- 1940066 TI - Moebius syndrome in association with hypogonadotropic hypogonadism. AB - The association between hypogonadotropic hypogonadism and multiple CNS lesions in a variety of disorders suggests a possible causative link between these clinical findings. Neural afferent input into the hypothalamus from higher CNS centers modulates GnRH secretion and derangements of these neural pathways could potentially result in diminished gonadotropin secretion and hypogonadism. This report describes a patient with multiple CNS defects secondary to Moebius syndrome and hypogonadotropic hypogonadism whose clinical features support the hypothesis that his CNS and endocrine defects may be causally associated. Comprehensive clinical evaluation in this patient revealed severe mental retardation; cranial nerve palsies; motor, reflex, and gait disturbances; and sexual infantilism secondary to hypogonadotropic hypogonadism. An MRI of the brain revealed atrophy or hypoplasia of the third cranial nerve and the olfactory gyri. Numerous syndromes including the Moebius syndrome are now described in which hypogonadotropic hypogonadism and CNS defects are associated. Detailed neuroanatomic and embryologic studies have demonstrated the important functional interrelationships between higher central nervous system centers and the hypothalamus. Taken together, these findings provide support for the causative association of multiple CNS defects and hypogonadotropic hypogonadism. PMID- 1940068 TI - Historical aspects about the development of our knowledge of morbus Basedow. PMID- 1940067 TI - Macroorchidism and testicular fibrosis associated with autoimmune thyroiditis. AB - A 16-year-old male with long-standing atrophic chronic lymphocytic thyroiditis was evaluated for macroorchidism. A testicular biopsy prior to treatment revealed peritubular and interstitial fibrosis, reduced spermatogenesis and sparse Leydig cells with nonprominent smooth endoplasmic reticulum. Biological/immunological LH and FSH ratios were reduced, I-LH and FSH response to GnRH was blunted, and levels of testosterone and androstenedione were low. Twenty-two months after thyroid treatment, the testicular size was unchanged, and the degree of fibrosis showed minimal regression. Spermatogenesis with normal morphology was present, Leydig cells with Reinke crystals were present, and surface area and diameter of the seminiferous tubules had increased only slightly. There was a normal I-LH and FSH response to GnRH, and normal levels of testosterone and androstenedione. This study, along with previous reports, suggests that the etiology of the hypothyroid state may influence the development of testicular fibrosis. PMID- 1940069 TI - Response to the Institute of Medicine report, "Extending Life, Enhancing Life: A National Research Agenda on Aging." The Gerontological Society of America. PMID- 1940070 TI - On models and the study of senescence: reflections on the state of biogerontology and a farewell. PMID- 1940071 TI - Stable Lyonization of X-linked pgk-1 gene during aging in normal tissues and tumors of mice carrying Searle's translocation. AB - We investigated whether age-dependent reactivation of a repressed X-linked gene occurs. Subjects were female mice, carrying the X-autosomal translocation, T(X;16)16H (Searle's translocation). The mice were also heterozygous, for the X linked gene coding for phosphoglycerate kinase (T16H pgk-1b/+ pgk-1a and pgk-1a was selectively repressed in these mice (McMahon and Monk, 1983). An electrophoretic method was applied to determine the PGK-1 allozyme patterns in blood, bone marrow, brain, gastrointestinal tract, liver, heart, spleen, and uterus (including tumor tissues when found). Samples were collected from mice of three different ages: 2 months (n = 4), 11 to 12 months (n = 10), or 18 to 21 months (n = 15). The lowest detection limit of the relative cellular population expressing the PGK-1A allozyme was found to be 2%, which was sensitive enough to detect the reported reactivation ratio (more than 10% of cells in a lower power microscopic field). We could not detect PGK-1A activity in any organ, including tumors in any age group, leading to the conclusion that reactivation of the repressed pgk-1a gene did not occur during aging. PMID- 1940072 TI - Exposure of rat muscle phosphoglycerate kinase to a nonenzymatic MFO system generates the old form of the enzyme. AB - The occurrence of age-related modifications in enzymes is a well-established symptom of aging that has been explained by several possible mechanisms including the oxidation of amino acid residues by mixed-function oxidation (MFO) systems. In the present study native old phosphoglycerate kinase was compared with young enzyme which had been modified by oxidation with ascorbate: FeCl3 followed by reduction. The comparison was done by monitoring the rates of heat denaturation of these enzyme forms, as well as their inactivation by trypsin. A remarkable similarity between the old and treated young enzyme was revealed, while native young phosphoglycerate kinase was inactivated with a different rate. Extensive unfolding followed by refolding converted both old and MFO-treated young phosphoglycerate kinase to species which greatly resemble the native young enzyme in their heat inactivation kinetics. These results demonstrate that the exposure of phosphoglycerate kinase to the mixed-function oxidation system introduces some modifications which are not reversed by subsequent enzyme reduction and which resemble those found in the native old enzyme. This mechanism, therefore, may account for the aging of phosphoglycerate kinase in vivo. PMID- 1940073 TI - Age- and dose-dependent naproxen disposition in Fischer 344 rats. AB - The effects of age and dose on the pharmacokinetics of naproxen were evaluated in young and senescent male Fischer 344 rats after 2.5 and 25 mg/kg doses. Pharmacokinetic parameters based on free naproxen concentrations demonstrated a significant decrease in free clearance and free steady-state volume of distribution in the aged rats. In vitro enzyme kinetic studies also demonstrated an age-related decline in the metabolic activity and affinity of the metabolic enzymes for naproxen in the aged rats. Plasma protein binding studies revealed a larger free fraction of drug in the plasma of senescent rats. Total clearance and steady-state volume of distribution were indistinguishable between young and old rats owing to the higher free fraction in aged rats. Dose had a significant effect with free clearance and free volume of distribution decreasing as dose increased. The binding of naproxen to plasma proteins was dependent on drug concentration. Unlike the parameters based on free naproxen concentrations, total plasma clearance and volume of distribution increased with increasing dose, due to the nonlinear protein binding. PMID- 1940075 TI - Postural sway characteristics of the elderly under normal and altered visual and support surface conditions. AB - One of the most pervasive findings in the literature on the aged is the general slowing of cognitive-motor responses with advancing age. Hence, an increased slowness in the processing of information from vestibular, visual, and somatosensory systems could contribute greatly to a decline in postural stability. To examine this question, in a cross-sectional investigation, postural sway behavior of elderly (n = 18) and young (n = 10) adults was examined under conditions that stressed the slower integrative mechanisms rather than the reflexive mechanisms of postural control. The postural sway behavior of young and elderly subjects was examined for a prolonged duration (80 s), under altered visual and/or support surface (5 cm thick foam surface) conditions, and contrasted with normal stance. Results showed that the exclusion or disruption of one of the sensory inputs, alone, was not consistently sufficient to differentiate between elderly and young adults, because of compensation by the remaining sensory sources. Both alterations together (i.e., visual and surface), however, had a substantially greater effect upon the elderly than the young. PMID- 1940074 TI - Aging and restriction of dietary calories increases insulin receptor mRNA, and aging increases glucocorticoid receptor mRNA in the liver of female C3B10RF1 mice. AB - We investigated the influence of age and a 20% or 52% reduction in dietary calories (caloric restriction) on expression of mRNA for a number of transcription factors and signal-transducing proteins using 4, 16, and 30-month old female mice of the long-lived C3B10RF1 strain. In all age groups, 52% caloric restriction, which extends maximum life span by approximately 33%, increased insulin receptor mRNA by 15% to 25% over the levels in animals fed ad libitum. Aging increased insulin receptor mRNA and glucocorticoid-receptor mRNA in all dietary groups. A similar increase in glucocorticoid receptor mRNA was not observed for male mice of three other strains, suggesting the change is sex- or strain-specific and not a general feature of aging. These changes appear to be specific. Neither caloric restriction nor age had an effect on the level of mRNA for insulin-like growth factor-I, RNA polymerase II elongation-factor S-II, or transcription factors Sp1, CCAAT and enhancer binding protein, or proto-oncogene c-jun. PMID- 1940076 TI - Compensation of the age-related decline in hippocampal muscarinic receptor density through daily exercise or underfeeding. AB - A decline in muscarinic receptor density of the hippocampus during aging has been previously observed. In the present investigation, the physiological treatments of underfeeding (every-other-day feeding) and exercise (daily treadmill running), initiated at 3 months or 10 months of age, compensated for this age-related decline in hippocampal muscarinic receptor density in F344 rats. Muscarinic receptor density in aged rats, 27 or 24 months of age, was maintained to levels comparable to rats 12 or 10 months of age, respectively. In addition, with the protocols used in this study, underfeeding appeared to be more effective than exercise in muscarinic receptor upregulation. PMID- 1940077 TI - The influence of visual factors on fall-related kinematic variables during stair descent by older women. AB - Despite the documented health hazards associated with stair descent, the mechanisms of falling on stairs remain relatively unexamined. The objectives of this study were to define kinematic variables that could be used to describe foot stair spatial relationships during the mid-stair phase of stair descent, and to investigate the effects of various visual and environmental conditions on those variables in a group of 36 healthy women between the ages of 55 and 70. Foot clearance and foot placement were measured through high-speed film analysis. Clearance between the foot and the stair during swing phase was small under all visual conditions. Degraded visual acuity had a significant effect on cadence, foot placement, and foot clearance, but visual surround conditions did not. The kinematic variables used in this experiment may be helpful in future studies to assess the results of interventions aimed at reducing the frequency of falls on stairs. PMID- 1940079 TI - Clinical spectrum of pulmonary tuberculosis in older patients: comparison with younger patients. AB - We compared the clinical-radiographic presentations of bacteriologically proven tuberculosis in 72 elderly (mean age: 71 yr) and 73 younger patients (mean age: 39 yrs). The tuberculin test (2 TU PPD) was positive in 55% and 92%, respectively. The prevalence of cough, dyspnea, anorexia, and weight loss was higher in the elderly (p less than .05), and night sweats were more prevalent in the younger patients (p less than .01). The radiographic pattern was not different between both groups (p greater than .10): "usual" apicoposterior lesions (with or without other abnormalities) were found in more than 70% of both groups; isolated "unusual" lesions consisted in both groups mainly of anterobasal infiltrations and sometimes of pleural effusions, rounded nodules, or miliary patterns. Yet, initially a wrong diagnosis was made more often in the elderly (p = .05). Malignancy, chronic pulmonary disease, and immunosuppression were more frequently encountered in the elderly (p less than .05), whereas alcoholism and smoking were more frequent in the younger patients (p less than .001). Tuberculosis-related mortality occurred in 6 elderly and 1 younger patient. PMID- 1940078 TI - Stepping over obstacles: gait patterns of healthy young and old adults. AB - Falls associated with tripping over an obstacle can be devastating to elderly individuals, yet little is known about the strategies used for stepping over obstacles by either old or young adults. The gait of gender-matched groups of 24 young and 24 old healthy adults (mean ages 22 and 71 years) was studied during a 4 m approach to and while stepping over obstacles of 0, 25, 51, or 152 mm height and in level obstacle-free walking. Optoelectronic cameras and recorders were used to record approach and obstacle crossing speeds as well as bilateral lower extremity kinematic parameters that described foot placement and movement trajectories relative to the obstacle. The results showed that age had no effect on minimum swing foot clearance (FC) over an obstacle. For the 25 mm obstacle, mean FC was 64 mm, or approximately three times that used in level gait; FC increased nonlinearly with obstacle height for all subjects. Although no age differences were found in obstacle-free gait, old adults exhibited a significantly more conservative strategy when crossing obstacles, with slower crossing speed, shorter step length, and shorter obstacle-heel strike distance. In addition, the old adults crossed the obstacle so that it was 10% further forward in their obstacle-crossing step. Although all subjects successfully avoided the riskiest form of obstacle contact, tripping, 4/24 healthy old adults stepped on an obstacle, demonstrating an increased risk for obstacle contact with age. PMID- 1940080 TI - Extension-induced changes in the microrelief of the human volar forearm: variations with age. AB - The skin microrelief can be assessed in vivo using a noninvasive method based on the image analysis of negative replicas, shadowed by oblique illumination. This technique was used to study changes in the surface furrows of the human volar forearm, related to the degree of extension, in volunteers of three age groups. Results confirmed that the skin in elderly subjects can be characterized by the lack of one of the two perpendicular furrow orientations observed in the young. During extension of the arm, the response of the microrelief in young subjects was clearly different from that in the elderly. Young skin buffered strain through a progressive shift in line density and furrow depth from one orientation to the other, whereas in the elderly, a progressive rotation of the single furrow orientation occurred. These differences would appear to be related to changes in the architecture and physical properties of the dermis. Microrelief, in the elderly subjects, showed a mean line density of 24/cm, regardless of the degree of extension. This constancy may reflect the ultimate stage in the chronological aging of the skin and may be characteristic of a loosened and relaxed dermis. PMID- 1940081 TI - Continuity and change in personality in old age--evidence from five longitudinal studies: introduction to a special issue. AB - This short essay introduces some of the current problems in developmental personality theory and comments on the five articles that follow, all of which arise from longitudinal studies of aging in Israel, Sweden, and the United States. Although the study of personality has always been of central interest in psychology, personality development in advanced old age is a very new topic. We hope that this Special Issue will stimulate a lively discussion and will provoke further studies of personality in old age, which is indeed a "special issue." PMID- 1940082 TI - Adult personality and psychomotor performance: cross-sectional and longitudinal analyses. AB - Results are presented from cross-sectional and longitudinal analyses of data from the Test of Behavioral Rigidity for 3,442 subjects over the age range from 22 to 84 years. Data are presented on the Behavioral Flexibility, Attitudinal Flexibility, and Social Responsibility questionnaire scales, as well as on performance score measures indexing Associational Flexibility, Instructional Set Flexibility, Copying Speed, and Associational Speed. Data on these scales were obtained for 5 samples examined 7 years apart (1956, 1963, 1970, 1977, and 1984). These data permit analyses of birth cohort differences and rate of change within the same individuals, as well as successive samples drawn from the same cohort over as long as 28-year periods. Results of the analyses confirm the presence of substantial generational differences, with generally only limited change over time within cohorts. PMID- 1940084 TI - The association of ancestral longevity with successful aging. AB - A cohort of 184 men from socioeconomically advantaged ancestors has been followed from ages 18 to 65. In order to test the hypothesis that ancestral longevity would predict both mental and physical vigor, the men's physical and psychosocial health have been prospectively monitored, and the age at death of their parents and grandparents obtained. Ancestral longevity was strongly predictive of chronic illness at age 60 +/- 1 years and mortality at age 68 +/- 1 years. Long-lived ancestors, however, exerted little effect in predicting psychosocial vigor and mental health at age 65. PMID- 1940083 TI - Stability and change of personality in old age and its relation to survival. AB - Stability of personality characteristics with increasing age was analyzed in a Swedish longitudinal study using a modified version of the Rod-and-Frame Test. This test was analyzed in a serial manner in order to emphasize cognitive style. Two important findings emerged. First, during the 6 years between the ages of 67 and 73, 80% of the study participants showed stability in the field independence dependence dimension. Second, stability of the field independence-dependence trait between ages 67 and 73 predicted survival to age 83, whereas destabilization (i.e., changes of Rod-and-Frame Test classification) was significantly associated with earlier death. In most cases, destabilization meant that field-independent subjects became field dependent. The results are discussed in relation to dispositional and situational factors. Causative factors for destabilization are hypothesized. PMID- 1940085 TI - Personality in advanced old age: continuity or change? AB - A longitudinal study of elderly persons found evidence of personality development even in advanced old age. Five traits, similar to traits found in younger persons, were identified. Although considerable continuity was found, change also was apparent. An increase in agreeableness was observed for the old-old, bringing their scores up to the level maintained by the oldest-old. Two traits were stable: satisfaction (65% did not change reliably) and intellect (63% did not change reliably). A decline in extraversion occurred in both age groups. Energetic, in which 40% declined, may be more affected than the other traits by external, environmental circumstances. The study confirms the findings of longitudinal studies of children and younger adults and extends them into the final stages of life. PMID- 1940086 TI - Who and how: some unanswered questions in adult development. AB - This study argues that a better understanding of the processes of life span and adult development can be reached if there is a distinction made between the concepts of stability and continuity. The latter implies both stability and change. To assess continuity, a model of personality development must be adopted that covers both general and differential aspects of its course during the life span. This makes it possible to identify and assess individual variations or types of individual development, as well as general developmental trends. Because statements about stability and continuity are inevitably contingent upon techniques of data collection and statistical methods, it is recommended that research designs should be used that permit comparison of normative and ipsative approaches to the same population. To illustrate and support this argument, the design and rationale of the Jerusalem Study of Psychological Development during Middle and Later Adulthood are briefly described, as well as the resulting personality types and their development as empirically identified by application of Q-technique. PMID- 1940087 TI - The use of the Lanthony New Color Test in determining the effects of aging on color vision. AB - The primary purpose of this study was to collect data on the loss of color vision as a function of age. The Lanthony New Color Test (NCT), which measures acquired losses of color vision in the dimensions of hue, saturation, and brightness, was used to compile data on 68 subjects. The minimum number of subjects were 10 per decade from age 30 to 90 years. An age gradient of selective loss of discrimination of saturation beginning at age 50 was demonstrated, with rapid change noted after age 60. Similar findings were seen for hue but were not evident for brightness. By age 70, a neutral zone emerged at blue/purple, Munsell chroma level 2. The instrument was shown to be reliable and valid in comparison to the Farnsworth Dichotomous Panel D.15. It is seen that this information will provide a basis for planning safer, more functional environments for elderly people. PMID- 1940088 TI - Psychophysics of reading--X. Effects of age-related changes in vision. AB - This study examined the influence of age-related changes in vision on reading performance. Maximum reading speed was measured in groups of young (n = 16, mean age 21.6 years) and old (n = 14, mean age 68.3 years) subjects, all with acuities of 20/32 or better. A psychophysical procedure was used for measuring reading speed that has proven reliable and sensitive to visual factors in previous research. Data were collected for character sizes ranging from .15 degrees to 12 degrees. Research revealed that old subjects who were free of eye disease read as fast as the young subjects for character sizes ranging from .3 degrees to 1.0 degrees. This is the range in which reading speed is maximum for young subjects. Research also revealed that old subjects showed a deficit when reading text composed of very small or very large characters. Their speeds dropped to about 70% of the young adult speeds. These deficits may be due to age-related losses in visual contrast sensitivity. PMID- 1940089 TI - Age differences in retrieval consistency and response dominance. AB - The probability of generating dominant responses and producing the same response on two occasions was compared for older and younger adults over three different intervals. Continuous retrieval from broadly defined semantic and orthographic categories was examined in Experiment 1; single-word retrieval from restricted categories was tested in Experiment 2 using a picture-naming task. There was no age difference in the tendency to generate normatively dominant responses in either experiment, but there were age differences in consistency. For broad categories, older were less consistent than younger adults at each intersession interval. With restricted categories, older adults showed a systematic decline in consistency over increasing intersession interval, while younger adults showed no change. Unlike prior research, we failed to find evidence for a positive relationship between verbal ability and response dominance. PMID- 1940090 TI - Aging, inhibitory processes, and negative priming. AB - The hypothesis that older adults experience a decline in the efficiency of inhibitory processes was tested in a negative priming experiment. Negative priming is interpreted as being due to the previous inhibition of a subsequent target item. An experiment involving a visual selective attention task with a negative priming condition was conducted with 20 college students and 20 older adults. A letter-reading task with partially superimposed red and green letters was used to assess age differences in negative priming. Subjects read red letters and ignored green letters. Results showed a significant interaction between age and the effect of distracting information, with older adults being more slowed by the presence of green letters than young adults. However, older adults failed to show negative priming effects, whereas young adults did show negative priming. These findings are interpreted in the context of age deficits in inhibitory processes, which may lead to decreased performance on selective attention tasks. PMID- 1940091 TI - Syntactic complexity and adults' running memory span. AB - This study investigated age group differences in adults' running memory span for prose. College students and adults 60 to 94 years of age listened to a prose passage that was interrupted occasionally by pauses. At each pause, the adults attempted to recall the immediately preceding text. The pauses followed either two single-clause sentences, a two-clause right-branching sentence, or a two clause left-branching sentence. There was a significant Age Group x Syntactic Form x Clause Order interaction such that the age group differences in verbatim recall were exacerbated by the effects of syntactic complexity. The elderly recalled 25% fewer words from the first embedded clause of the left-branching sentences than the college students, whereas they recalled only 4% fewer words from the first of two successive single-clause sentences. Performance on the running memory span task was also correlated with two measures of the adults' working memory: forward digit span and backward digit span. The pattern of correlations indicated that working memory limitations determine adults' running memory span for prose and contribute to age-group deficits in comprehension. PMID- 1940093 TI - Predictors of behavioral disturbance in Alzheimer's disease. AB - The relationship of behavioral disturbances in Alzheimer's disease to disease severity, age at onset, and the presence of extrapyramidal signs was investigated in three studies. Five categories of behavior disturbance were ascertained through structured interview with the patient's primary caregiver: apathy, agitation, psychotic symptoms, disinhibition, and irritability. In Study 1, measures of disease severity accounted for 42% of the variance in the Apathy scale but less than 20% of the variance in the remaining scales. In Study 2, the presence of extrapyramidal signs was associated with increased Apathy and moderated the association between disease severity and the Psychotic Symptoms and Irritability scales. In Study 3, age at onset was associated with the Agitation scale and moderated the association between disease severity and the Apathy, Psychotic Symptoms, and Irritability scales. The findings are discussed in terms of the clinical heterogeneity within Alzheimer's disease, the possible biological bases of these behavioral disturbances, and the psychometric issues pertinent to their measurement. PMID- 1940092 TI - Long-term effects of exercise on psychological functioning in older men and women. AB - The purpose of this study was to determine the psychological, behavioral, and cognitive changes associated with up to 14 months of aerobic exercise training. For the first 4 months of the study, 101 older (greater than 60 years) men and women were randomly assigned to one of three conditions: Aerobic exercise, Yoga, or a Waiting List control group. Before and following the intervention, all subjects completed a comprehensive assessment battery, including measures of mood and cognitive functioning. A semi-crossover design was employed such that, following completion of the second assessment, all subjects completed 4 months of aerobic exercise and underwent a third assessment. Subjects were given the option of participating in 6 additional months of supervised aerobic exercise (14 months total), and all subjects, regardless of their exercise status, completed a fourth assessment. Results indicated that subjects experienced a 10-15% improvement in aerobic capacity. In general, there were relatively few improvements in cognitive performance associated with aerobic exercise, although subjects who maintained their exercise participation for 14 months experienced improvements in some psychiatric symptoms. However, the healthy subjects in this study were functioning at a relatively high level to begin with, and exercise training may produce greater improvements among elderly with concomitant physical or emotional impairments. PMID- 1940094 TI - Imipramine in the treatment of depressed Alzheimer's patients: impact on cognition. AB - A double-blind study evaluated the impact of imipramine on cognitive function in 61 patients with Alzheimer's disease. Twenty-eight patients had coexistent depression and dementia; 33 had dementia only. All were randomly assigned to an 8 week trial of imipramine or placebo. For both depressed and nondepressed subjects, the effect of imipramine on cognition was minimal. A subtle decrement in general cognitive function was evident in those treated with imipramine, as compared with those treated with placebo. No effects were observed on memory. Clinicians are advised that very low doses of imipramine (25 mg/daily) may be tolerated in depressed Alzheimer patients, but that cognitive changes do occur in some patients and should be carefully monitored. PMID- 1940095 TI - Elders' schema for taking medication: implications for instruction design. AB - We examined whether elders share a schema for taking medication and if instructions are better understood and recalled when organized to match this pre existing schema. Experiment 1 investigated if elders agree on how to group medication information into categories, and if they agree on an order for arranging this information. Elders tended to organize information into three categories, arranged in the following order: General information about the medication (purpose), How to take (dose and schedule), and Outcomes (emergency information). In Experiment 2, we compared instructions that were: (a) compatible with this schema in terms of grouping and order, (b) compatible only in terms of grouping (category order was changed), and (c) incompatible, not matching the model in terms of either grouping or order. Memory for medication information increased with the compatibility of the instructions to the model. Elders also preferred the more compatible instructions. The findings suggest that elders possess a schema for taking medication, which they use to understand and recall medication instructions. PMID- 1940096 TI - The economic impact of prospective population changes in advanced industrial countries: an historical perspective. AB - Demographic projections to the year 2050 for advanced industrial nations, implying low or negative population growth and a sharp rise in old age dependency, have created concerns about the long-term economic outlook in these countries. An analysis of these projections in the light of the demographic and economic experience of the past century raises doubt about these concerns. There is little empirical evidence that declining population growth has slowed the rate of economic growth. Although the burden of aged dependents will reach a new high, the projected total dependency rate is not out of line with prior experience. Thus, the ability of the working population to shoulder the burden of higher taxes to support programs for older dependents will be greater because of reduced needs to support younger dependents. This conclusion holds for a number of variant projections, the only clear exception being one that implies a mortality revolution at older ages. PMID- 1940097 TI - Patterns of economic change surrounding the death of a spouse. AB - The timing of economic changes near the death of a spouse is not well understood. Using multiple regression analysis and longitudinal data from the Panel Study of Income Dynamics, the economic situations of middle-aged and older widows and widowers were compared to those of otherwise similar intact couples over an 11 year period. The analysis shows that all four widowed groups had fewer economic resources 5 years after the death than did their married counterparts. Yet, each group took very different economic paths to get to this point. For example, older widows and widowers begin the analysis with significantly lower income-to-needs ratios 5 years prior to the death, while middle-aged widows experience more economic change near the time of the death. These findings suggest that both middle-aged and older cohorts of widowed individuals may have made consumption choices over the life cycle that differ from those made by their intact counterparts. PMID- 1940098 TI - Cultural differences among elderly women in coping with the death of an adult child. AB - This article describes differences between elderly Jewish and non-Jewish women in dealing with the death of an adult child. Dimensions of difference include the meaning of the death to the mother, her expression of grief, and her conceptualization of the future in the face of the loss. Results are based on data from 12 Jewish and 17 non-Jewish women taking part in a larger study examining generativity as a predictor of well-being in women over 60. Data collection included in-depth life histories and quantitative evaluations of well being, affect, generativity, and personality variables associated with mothering. Qualitatively, Jewish women were depressed and fixed in grief, with the loss remaining central to their lives. Non-Jewish women articulated philosophies of acceptance, putting the death in a perspective that enabled them to move beyond their loss. Well-being, affect, generativity, and personality measures statistically supported the qualitative differences found between the groups. PMID- 1940099 TI - The effects of early family relationships on contemporary relationships and assistance patterns between adult children and their parents. AB - We investigated the influence of early parent-child relationships on contemporary adult child-parent relationships and the effects of these relationships on the level of assistance between adult child and parent. A sample of 902 married men and women were questioned regarding their current relationships with their elderly parents, the level of assistance provided them, and the quality of their relationship with their parents when they were growing up. The findings indicated that early parent-child relationships and the characteristics of parents when adult children were growing up influenced contemporary adult child-parent relationships. In turn, the quality of the contemporary adult child-parent relationship was found to have a slight effect on assistance from adult children to their parents. PMID- 1940100 TI - Sexual relations in later life: a national study of married persons. AB - Sexual behavior among married persons 60 years of age and older was examined using data from the National Survey of Families and Households. About 53 percent of the entire sample, and 24 percent of those 76 years of age and older, report having had sexual relations at least once within the past month. Persons who have been sexually active within the past month report having sex about four times during the month. While respondent's age is significantly related to sexual behavior, the monthly incidence and overall sexual frequency variables are not influenced by gender, race, or a Gender by Spouse's Health Status interaction term. While the NSFH variables included in our model are poor predictors of elderly persons' sexual behavior, analyses reveal that a person's sense of self worth/competence and his/her partner's health status are significantly and positively related to the incidence of sex within the past month. PMID- 1940101 TI - The use of health services by older adults. AB - Using baseline data on the 5,151 respondents surveyed as part of the panel design of the Longitudinal Study on Aging (LSOA), this article estimates, cross sectionally, the relationships hypothesized in the behavioral model of health services utilization. In addition to the traditional indicators of the predisposing, enabling, and need characteristics, the richness of the LSOA permits the inclusion of measures of multigenerational living arrangements, kin and nonkin social supports, health worries and the sense of health control, health insurance coverage, residential stability, and several multiple-item scales of functional limitations. Despite these innovations, the ability of the behavioral model to accurately predict the use of health services by older adults remains relatively unchanged. Important conceptual clarifications involving the hypothesized relationships, however, are identified and discussed. PMID- 1940102 TI - The effect of retirement on health services utilization: the Kaiser Permanente Retirement Study. AB - The relationship of retirement and use of medical services was investigated among members of the Kaiser Permanente Medical Care Program in Northern California. A mailed survey of a 10 percent random sample of members 60-66 years old (N = 10,202) was followed by a telephone interview of (a) all respondents who had planned to retire in the next year, and (b) a random sample of respondents who had not planned to retire: 253 had retired (Retired group) and 238 were still working 20 hours a week or more (Not Retired group). Medical charts were reviewed for one year before and after the retirement date for the Retired group and for one year before and after a randomly assigned anchor date for the Not Retired group. With the exception of urgent care and emergency visits, no significant difference was found between the two groups in overall use of outpatient and inpatient services following retirement. PMID- 1940103 TI - A literature review: HIV seropositivity in the elderly. AB - 1. AIDS affects all segments of the population, including the elderly. Elders at risk are recipients of blood products prior to 1985 and their spouses; and persons having unprotected anal or vaginal intercourse outside of a mutually monogamous relationship. 2. Because of stereotyping and lack of awareness, health care professionals have underserved the needs of the elderly for AIDS care. 3. Elderly persons experience the manifestations of HIV in unique ways, and the consequences of the infection are particularly destructive to their lifestyles and support systems. 4. There is an acute need for nursing intervention in the area of AIDS education targeted to the elderly population. In addition, nurses should be at the forefront of development of a comprehensive home health plan geared specifically for the elderly AIDS client. PMID- 1940104 TI - Nurse empathy to caregivers of chronically ill elders. AB - 1. Findings showed that differences exist with regard to the amount of strain family caregivers experience and how caregivers perceive the nurses' empathy. 2. Caregivers to older persons requiring more health care services experienced more objective strain (ie, lack of time or more physical demands) than caregivers to persons who required less health care services. 3. Caregivers in isolated environments viewed nurses as more empathic compared with caregivers residing in areas where there was opportunity for more interaction with others. PMID- 1940105 TI - Teaching the elderly stress reduction. AB - 1. Psychological or physiological stressors cause changes within the body through the action of the hypothalamus. 2. There are several techniques for stress management, including progressive muscle relaxation and guided imagery. 3. The nurse can teach stress management techniques to the elderly using teaching modifications to respond to changes due to aging. 4. The nurse can teach stress management in various settings to clients who have a nursing diagnosis such as anxiety, alteration in comfort, or sleep pattern disturbance. PMID- 1940106 TI - The development of ethical thought in long-term care. AB - 1. Pervasive medical technology influences treatment decisions in long-term care. Clinical decision-making is enhanced by the development of an ethical thought process among staff. 2. Disagreements among staff about the appropriateness of clinical decisions can lower staff morale and negatively affect the work environment. 3. Staff education about ethical principles and how they influence decision-making helps to define the patient's rights and the caregiver's responsibilities. 4. The use of staff experiences in teaching ethical principles is successful in educating all levels of staff about everyday ethics in long-term care. PMID- 1940107 TI - Clearing up the confusion: adverse effects of medications in the elderly. AB - 1. Physiological changes normally seen in elderly patients affect the pharmacodynamics of medications and may contribute to adverse effects. 2. A large number of medications can potentially cause confusion as an adverse effect in the vulnerable elderly patient. 3. Inadequate patient education contributes to noncompliance and errors in self-administration of medications. 4. A high index of suspicion is indicated when the nurse observes changes in mental status in the older adult after a new prescription is begun, when multiple medications are taken, and when some medications have been taken for extended periods. PMID- 1940108 TI - Gerontological nursing. Faculty preparation for teaching. AB - 1. As the number of older adults in the US increases, nurse educators must be prepared to teach gerontological nursing to their students. A 3-year project addresses the need for faculty development in gerontological nursing. 2. A major objective of the project is to provide basic knowledge of gerontological nursing to regional nursing faculty through a series of 1-week workshops that include didactic content and clinical observation experiences. 3. All 1990 workshops were filled to capacity, with participants exhibiting wide variation in their gerontological knowledge base. PMID- 1940109 TI - Three wise phrases: "thank you," "I love you," and "goodbye". PMID- 1940110 TI - Geriatric tinnitus: causes, clinical treatment, and prevention. AB - 1. Tinnitus is seldom recorded in the clinical database of the elderly, despite the fact that next to hearing loss, tinnitus is the most commonly reported ear problem by the elderly population. 2. Common problems of the elderly that demand special counseling and teaching skills of the nurse are decreased tolerance to tinnitus due to coexistent complex morbidity, social problems, and losses; worry that the tinnitus is a sign of an impending crisis, such as stroke, brain tumor, or insanity; and boredom with excess time with little to do but to listen to one's tinnitus. 3. Tinnitus in aging is a symptom that is usually due to an identifiable disease, and is rarely of subjective type, high-pitched quality, chronic, irreversible, idiopathic, and bilateral. 4. The common causes and aggravating factors about tinnitus in aging can provide the clues to effective nursing-initiated measures, many of which are simple household activities or personal interactions. PMID- 1940111 TI - Age and health perceptions among elderly blacks. AB - 1. By the year 2000, minority group members will comprise 20% of the total elderly population. Three million blacks will be 65 years or older by that time. 2. Many health-care providers have limited knowledge, experience, or understanding of the minority perspective as it relates to those decisions that influence the health and illness behaviors of this underserved group. 3. A person's self-perception of his physical and mental abilities, as well as his own health status, will influence his willingness to seek and accept help. 4. Interacting with the black elderly about age and health perceptions can allow nurses to demonstrate personal interest, obtain pertinent health-related data, and gain insights into the coping strategies that these individuals have successfully used for long periods. PMID- 1940112 TI - A clinical possibility: preventing health problems after the age of 65. AB - 1. There are a number of common health problems of the elderly that have the potential to be prevented, postponed, or reversed even after age 65. 2. The nurse's knowledge of the difference between normal aging and a disease process is essential to enable the nurse to detect whether a health problem can be prevented, postponed, or reversed. 3. It is being discovered that there is an alarmingly high number of seniors whose "dementia" is not permanent, but rather is reversible or treatable. PMID- 1940113 TI - The prevalence of orthostatic hypotension in high-risk ambulatory elders. AB - 1. Orthostatic hypotension may be a serious threat, especially among the elderly. It may be characterized as a change in diastolic or systolic blood pressure, a narrowing of pulse pressure, or tachycardia. 2. Physiological changes of aging super-imposed on illness or the use of medications appear to contribute to the prevalence of orthostatic hypotension and its symptoms. It is the combination of known risk factors of debility, medications, and common geriatric illnesses, such as diabetes, that notably create the symptoms. 3. Nurses can do much to reduce the associated symptoms and threat of synergistic effects on blood pressure. Careful measurements of blood pressure and pulse in various positions should be incorporated into routine nursing practice. Management of patients with orthostatic hypotension necessitates that nursing interventions be aimed at preventing injuries from associated falls. PMID- 1940114 TI - Crisis intervention: elders awaiting placement in an acute care facility. AB - 1. Awaiting nursing home placement may be viewed as a situational crisis for elders in acute care facilities. 2. Crisis intervention techniques focus on solving the immediate problem in the person's life to re-establish emotional equilibrium in the individual. 3. The more predictable the new nursing home environment is to the elder, the less negative the effects of relocation. 4. Ethically, it must be assumed that cognitively impaired elders will benefit from some form of crisis intervention prior to nursing home relocation. PMID- 1940115 TI - Urinary incontinence: nursing home staff reaction toward residents. AB - 1. ISQ-SR is a reliable and valid tool to measure psychological stress associated with working with urinary incontinent patients. 2. ISQ-SR can be used to measure efficacy of continuing education programs aimed at reducing staff stress associated with urinary incontinence. 3. Eighty percent of the staff reported that they looked for ways to help patients with their incontinence all the time, but only 50% said that they felt comfortable working with urinary incontinent patients all of the time. 4. Sixty-three percent of the staff reported that they felt frustrated about working with urinary incontinence some of the time, indicating a need for continuing education. PMID- 1940117 TI - Nutritional status of institutionalized older Americans. PMID- 1940116 TI - Tips on promoting food and fluid intake in the elderly. AB - Nurses have a crucial role in ensuring adequate food and fluid intake in the elderly. Nurses can improve the nutritional intake of their elderly patients by obtaining proper nutritional assessments, addressing risk factors for malnutrition and fluid deficit, providing enough staff and volunteers to help feed impaired patients, honoring each older person's meal pattern, scheduling drug regimens that do not interfere with food and fluid intake, not scheduling food-related activities and visits too near mealtime, serving food that is palatable and attractively served, ensuring adequate fluid intake, and being creative in finding ways to keep the restless, wandering patient well-nourished and hydrated. Monitoring food and fluid intake requires precise recording of what foods and fluids the older person is ingesting, keeping accurate intake and output records, determining periodic weights, informing the physician of patients' weight loss in a timely manner, and instituting corrective measures at once. PMID- 1940118 TI - Clinical considerations. Midlife daughters and their aging parents. AB - 1. As North America ages, complex parent care issues are becoming part of the lives of already busy midlife daughters. 2. The midlife daughter involved in parent care is at risk for becoming a "hidden patient" in the health-care system. 3. Group intervention with midlife daughters helps them to anticipate and avoid the stress of elder care to learn coping skills and to access support. PMID- 1940119 TI - Neuropathologic findings in patients receiving long-term vigabatrin therapy for chronic intractable epilepsy. AB - Vigabatrin is a new antiepileptic drug that acts by the irreversible inhibition of gamma-aminobutyric acid (GABA) aminotransferase. During animal safety testing, vigabatrin was found to cause reversible intramyelinic edema in the brains of rodents and dogs but not in primates. In humans, the drug is well tolerated, and extensive clinical, neurophysiologic, neurochemical, and psychometric testing has failed to demonstrate any evidence of neurotoxicity. Neuropathologic examination has now been carried out on 62 patients with refractory epilepsy, who were on vigabatrin therapy either prior to undergoing neurosurgery for their epilepsy or before death. A further ten similar cases have been included in the study from age-matched patients with refractory epilepsy who had not been treated with vigabatrin prior to surgery or death. None of the neuropathologic changes seen in the preclinical animals studies have been observed in the human cases. In no case was there considered to be any evidence of myelin microvacuolation or myelin sheath splitting that could be attributed to vigabatrin treatment. Demyelination has never been observed in either the animal or human material. These findings support the clinical tolerability seen in long-term treatment. PMID- 1940120 TI - Vigabatrin in refractory epilepsy in adults and its application in children. AB - Vigabatrin has been studied in adult drug-resistant epilepsy since 1982 in single blind and double-blind studies followed by long-term, open evaluations. These studies have provided evidence that vigabatrin is a potent and well-tolerated antiepileptic drug and support its potential value in pediatric epilepsy. The lack of any evidence of human neurotoxicity in these patients is also reassuring regarding its use in children. PMID- 1940121 TI - Vigabatrin: a new antiepileptic medication. PMID- 1940123 TI - Vigabatrin in pediatric epilepsy--an open study. AB - The antiepileptic effect of vigabatrin in adults has been demonstrated in a number of controlled studies. In children, the effect of vigabatrin has been investigated only to a limited extent. In order to assess the long-term effect and safety of vigabatrin in patients with severe epilepsy, an open, add-on, dose ranging study was initiated. To date, 27 children with partial epilepsy, two with generalized epilepsy, two with Lennox-Gastaut syndrome, and one with nonclassifiable epilepsy have been enrolled in the trial. Fifty-four percent of patients have experienced a greater than 50% reduction in seizure frequency, and four patients have become seizure free. A significant reduction in seizures was noted across the patient population, although patients who were recorded as seizure free at 3 and 6 months did suffer some recurrence of seizures. However, when seizures recurred, they did so at much lower frequency than recorded at the start of the study. Thirteen patients (39%) reported adverse events attributable to vigabatrin; one was immediately withdrawn from the study, and six had their vigabatrin dose reduced. No physiologic effects were noted on normal growth or clinical physical examination. PMID- 1940122 TI - Vigabatrin in childhood epilepsy. AB - Sixty-six children with various types of severe drug-resistant epilepsy were entered into a long-term, dose-rising study of vigabatrin after a 4-week run-in placebo period. All the children were receiving one to three other antiepileptic drugs, the doses of which were not changed during the 6-month dose titration phase. Following the introduction of vigabatrin, 11 patients became seizure free, and 28 responded with a greater than 50% reduction in seizure frequency. The following types of epilepsy responded favorably in order of decreasing efficacy: cryptogenic and symptomatic partial epilepsy, other symptomatic generalized epilepsy, and Lennox-Gastaut syndrome. However, three of nine patients with myoclonic epilepsy showed an increase in seizure frequency. Optimal responses were found with vigabatrin doses of 40 to 80 mg/kg/day, although no significant adverse effects were noted with doses of higher than 100 mg/kg/day. Thirty-eight responders continued on vigabatrin, 19 of whom have been treated for more than 1 year, with generally good efficacy. As a result of discontinuing concomitant antiepileptics, six patients are on monotherapy with vigabatrin, four of whom are seizure free. Vigabatrin tolerability was good, with 39 of 66 children reporting no adverse effects. Hyperkinesia was reported in 17 patients (26%), and two had to drop out of the study. All these patients had a history of hyperkinesia or mental retardation. In patients in whom vigabatrin dose was reduced because of hyperkinesia, a dose increase could later be instituted without recurrence of symptoms. There was no change in neurologic examination and no drug-related abnormalities in clinical laboratory data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940124 TI - Dose-response study of vigabatrin in children with refractory epilepsy. AB - Twenty children aged 2 months to 18 years were included in a dose-response study of vigabatrin as add-on therapy to preexisting antiepileptic drugs (up to two per patient). All children had severe refractory epilepsy: partial seizures with or without secondary generalization in 19, and myoclonic seizures in one. After a 2 month observation period and a 1-month add-on placebo period, a fixed dose of add on vigabatrin was given for 2 months: 1, 1.5, or 2 g/day, according to body weight (mean dose, 60 mg/kg/day). Three patients (15%) became seizure free, and nine (45%) showed a 50% to 99% reduction in seizure frequency. In the 17 patients whose seizures were not totally suppressed, vigabatrin dose was increased for a further 2 months, and in 7 patients who still showed less than 50% reduction in seizure frequency, vigabatrin dose was increased again. Efficacy appeared unchanged by these higher doses. During a 9-month follow-up phase, no tolerance to the effects of vigabatrin was observed, with three children seizure free and 13 (65%) reporting a 50% to 99% reduction in seizure frequency. During the study, adverse effects were recorded in three children (15%), namely drowsiness, constipation, fatigue, and apathy. These effects were generally transient, being observed during the dose-modification phase and disappearing either spontaneously or on reduction of vigabatrin dose. Clinical and laboratory tolerability to vigabatrin appeared to be very good, with no patients having withdrawn from the study because of side effects. A slight reduction in red blood cell count and hemoglobin levels was noted but was of doubtful clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940126 TI - Randomized controlled pilot study of vigabatrin versus carbamazepine monotherapy in newly diagnosed patients with epilepsy: an interim report. AB - At present, 34 patients aged 15 to 63 years with newly diagnosed epilepsy have been randomly assigned to vigabatrin (n = 17) or carbamazepine (n = 17). Evaluation of clinical data, neuropsychological assessment, quantitative spectral electroencephalogram (EEG), and somatosensory- and visual-evoked potentials at baseline and after a 3 months' maintenance phase are presented for 12 patients on vigabatrin and for 11 patients on carbamazepine. Among these patients, retention rate in the maintenance phase of the study is 75% for vigabatrin patients (two noncompliant patients and one nonresponder dropped out) followed up for a mean of 11 months (range, 5 to 16 months). The retention rate for carbamazepine is 100% for the 11 patients, followed up for a mean of 9 months (range, 3 to 17 months). Patients receiving vigabatrin showed significant improvements in sustained concentration and tasks requiring flexible mental processing after the 3-month maintenance period, compared to baseline. In the carbamazepine group, there was improvement only in delayed list recall, and in contrast, errors in visuomotor tasks requiring processing increased significantly. Patients on carbamazepine demonstrated slowed occipital mean frequencies, but vigabatrin treatment was not associated with any significant quantitative EEG changes. Significant prolongation of somatosensory-evoked potential N19 latencies was seen with both carbamazepine and vigabatrin. PMID- 1940125 TI - Therapeutic trial of vigabatrin in refractory infantile spasms. AB - Infantile spasms usually start during the first year of life and constitute one of the most difficult types of epilepsy to treat. They carry a very poor prognosis for both epilepsy and mental development. Seventy children, including 47 infants, with intractable infantile spasms were entered into an open study with vigabatrin as add-on therapy to the usual anticonvulsant treatment. All were resistant to previous treatments, including corticosteroids (43 patients), carbamazepine, benzodiazepines, and sodium valproate. Two children withdrew from the study because of intolerance to vigabatrin (hypotonia or hypertonia) before evaluation of efficacy could be made. Of the remaining 68 children, 29 (43%) showed complete suppression of spasms. Forty-six children had a greater than 50% reduction in spasms. The best response was observed in those with tuberous sclerosis (12/14 compared with 12/18 with symptomatic infantile spasms of other origin and 22/36 with cryptogenic infantile spasms). Following the initial response to treatment of these patients (n = 68), a long-term response was confirmed in 75% of children with symptomatic infantile spasms and 36% of children with cryptogenic infantile spasms. In eight children, all other anticonvulsant medication could be definitively withdrawn. Tolerability appeared excellent, with 52 of 70 patients reporting no side effects. Somnolence, hypotonia, weight gain, excitation, and insomnia were the most common problems at the beginning of the study and were usually transient. Given the poor prognosis of this type of childhood epilepsy, vigabatrin appears to be a very interesting advance in the management of drug-resistant infantile spasms. PMID- 1940127 TI - Pharmacology and clinical pharmacology of vigabatrin. AB - Vigabatrin is an enzyme-activated, irreversible inhibitor of gamma-aminobutyric acid (GABA) aminotransferase, which causes a marked increase in cerebral GABA concentration and a resulting anticonvulsant action. Recovery from its effects requires the synthesis of new enzyme, and this may take several days following a single dose. The pharmacokinetics of vigabatrin are not a good guide to its duration of action. It is cleared rapidly by renal elimination (giving a plasma half-life of approximately 7 to 9 hours), and therefore the effect of the drug long outlasts its presence in the body. Plasma drug level monitoring is therefore of little value in regulating vigabatrin therapy. The drug is not bound to plasma proteins. Interactions with other drugs would not be expected because of its predominant renal elimination and its lack of protein binding. Also, vigabatrin does not induce liver enzymes, as do many of the standard antiepileptic drugs. In several trials, however, a small but significant reduction in phenytoin levels has been seen following the addition of vigabatrin to the antiepileptic medication. The mechanism for this reduction in phenytoin levels has not yet been elucidated, though it does not appear to be of clinical significance. PMID- 1940128 TI - Neural tube defects: epidemiology. PMID- 1940129 TI - Organic acidurias: a review. Part 2. AB - Laboratory findings are an essential part of the diagnostic approach to organic acidemias. In most organic acidemias, metabolism of glucose, ketone bodies, and ammonia is deranged primarily or secondarily, in addition to derangement of the acid-base balance. Hypoglycemia, lactic and/or ketoacidosis, and hyperammonemia of varying severity accompany the overt or compensated acidosis. In most instances, a definite diagnosis will be achieved by gas chromatography/mass spectrometry (GC/MS) studies of the urine. We detail the pattern of excreted organic acids in the major disorders. When the diagnosis reached by clinical and laboratory assessments is not conclusive, it must be supported by loading tests. We list the available methods of demonstrating the putative enzyme deficiency in the patient's cells and tissues. The majority of organic acidemias may be treated by limiting the source of or removing the toxic intermediary metabolite. We provide lists of available diets, supplements, and medications. In some instances, residual defective enzyme activity may be stimulated. We describe symptomatic management of the disturbed acid-base and electrolyte balance. PMID- 1940130 TI - Anencephaly in the United States, 1968-1987: the declining incidence among white infants. AB - The ethical issues concerning the use of fetal tissue as a source for organ transplantation has focused interest on anencephaly. For reasons that are not entirely clear, the incidence of anencephaly has been declining. As anencephaly is easily recognized and invariably fatal, mortality figures provide an excellent reflection of incidence. In the United States, between 1968 and 1987, infant mortality rates per 100,000 live births due to anencephaly declined from 22.4 to 12.1 (46.0%) for male infants and from 32.7 to 16.6 (49.2%) for female infants. However, when separated by race, the mortality rate declined for white male infants from 25.0 to 13.3 (46.8%) but only decreased from 9.0 to 7.7 (14.4%) for nonwhite male infants. The mortality rate declined for white female infants from 36.7 to 17.6 (52.0%) and actually increased slightly from 12.8 to 13.2 (3.1%) for nonwhite female infants. Thus, the declining incidence of anencephaly reflects a declining incidence of affected white infants but not of affected nonwhite infants. PMID- 1940131 TI - Learning disabilities in children with congenital adrenal hyperplasia. AB - Early exposure to androgens may be a cause of the higher incidence of learning disabilities among males. To test this hypothesis, we determined the frequency of learning disabilities, as measured by extent of Wechsler Verbal-Performance IQ discrepancy, among female patients with congenital adrenal hyperplasia, who are exposed in utero to excess androgens for their sex. A significantly larger Verbal Performance IQ discrepancy (10.1 vs 7.7) was found for the 18 female patients than for 27 unaffected female siblings (P = .045, one-tailed). The Verbal Performance IQ discrepancy of the females with congenital adrenal hyperplasia is in the male range (10.4 to 13.4), similar to males with congenital adrenal hyperplasia (n = 20) and unaffected male siblings (n = 31). In addition to the sex effect, there is an effect of the type of congenital adrenal hyperplasia on the frequency of learning disabilities. Simple virilizers are more likely to be learning disabled than salt-wasters (P = .04, one-tailed). However, salt-waster patients have a lower IQ (104 vs 117) than simple virilizer patients (P = .005, one-tailed). Presumably, this is because some salt-waster patients suffer brain injury from episodes of hypotension and hyponatremia. The diffuse insult to the central nervous system may overide the androgen effect and result in a general cognitive impairment. Because of this confounding effect on IQ in the salt-waster form of congenital adrenal hyperplasia, the simple virilizer female versus unaffected female siblings reprsents the best test of the hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940132 TI - Unusual variants of infantile spasms. AB - During evaluation of video-electroencephalograms (EEGs) performed in our laboratory, we identified 11 patients who had unusual repetitive movements that appeared to be variants of infantile spasms. Movements included yawning, facial grimacing, eye movements, and transient focal motor activity. These symptoms coincided with generalized attenuation, slow-wave transients, or other EEG ictal changes characteristic of infantile spasms. The background EEGs showed true or modified hypsarrhythmia. This series of patients shows that infantile spasms may be extremely subtle and clinically atypical. Patients who have these variants may or may not also have typical infantile spasms. In some patients, the seizures appear to be time-related or medication-induced modifications of more typical infantile spasms. PMID- 1940133 TI - Lorazepam in the treatment of refractory neonatal seizures. AB - We report the results of treatment of intractable seizures with lorazepam in seven neonates. All of the patients were part of a prospective study, who failed to respond to 40 mg/k of phenobarbital. Lorazepam was given intravenously at 0.05 mg/k and repeated up to a total dose of 0.15 mg/k if necessary. The diagnosis of seizures and the efficacy of treatment was assessed clinically and by EEG during the administration of lorazepam in three patients and on clinical grounds in four patients. Six patients were full term and one was premature; there were five males and two females. Four patients had hypoxic-ischemic encephalopathy, two had intracranial hemorrhage, and one had bacterial meningitis. Two patients received one dose of lorazepam, three received two doses, and two received three doses. Six patients responded with a complete cessation of seizures within three minutes of their last dose; the remaining patient (who received two doses) had a reduction in seizures. No patients developed apnea or hypotension during or immediately after the infusion of lorazepam and no other adverse effects were observed. Four patients remained seizure-free for the rest of the neonatal period and no other anticonvulsant medications were added. Seizures recurred in one patient at 16 hours; subsequent intermittent seizures were managed with additional phenobarbital. In another patient, seizures recurred at 12 hours and subsequent intermittent seizures were managed with phenytoin. In one patient, seizures continued with reduction of frequency and duration. We conclude that lorazepam may be effective in the treatment of neonatal seizures refractory to phenobarbital and that further treatment with intravenous phenytoin may be unnecessary under these circumstances. PMID- 1940134 TI - Muscle biopsy and the clinical course of infantile spinal muscular atrophy. AB - Eight infants with severe early infantile spinal muscular atrophy diagnosed by clinical presentation and muscle biopsy were studied. The extent of alterations in muscle histology, histochemistry, and ultrastructure did not reflect the relative severity of the clinical presentation or the course of the illness. In seven biopsies, ultrastructural studies demonstrated empty sleeves of basal lamina projecting from the surface of small myofibers. We conclude that severe infantile spinal muscular atrophy often results in myofiber atrophy similar to that found in other motor neuron diseases, and it is not solely a hypotrophic process. Muscle biopsy findings are important because they help to establish the diagnosis, but they do not help predict the severity of disease among infants with this condition. PMID- 1940135 TI - Selective type II muscle fiber hypertrophy in severe infantile spinal muscular atrophy. AB - The diagnostic muscle biopsy finding in severe infantile spinal muscular atrophy (Werdnig-Hoffmann disease, SMA type 1) is considered to be large-group atrophy with isolated clusters of hypertrophic type I myofibers. We present a unique case of severe infantile spinal muscular atrophy with selective hypertrophy of type II myofibers. A male infant presented at age 2 months with breathing difficulties and by age 4 months was hypotonic and weak. Electromyography revealed denervation in all extremity muscles, and nerve conduction velocities were normal but with small compound muscle action potentials. Quadriceps muscle biopsy revealed many hypertrophied type II myofibers (myofibers with a mean least diameter of 25.4 microns). In contrast, the largest type I myofibers were 20 microns in least diameter (mean diameter, 14.9 microns), and there was a normal-size population of type II fibers (mean diameter, 15.7 microns). In addition, sheets of atrophic type I and type II fibers averaged 2.0 microns in least diameter. Sural nerve biopsy was normal. Breathing difficulties progressed, with death ensuing at age 5 1/2 months. Autopsy revealed atrophy of ventral spinal roots with normal dorsal roots. There was loss of anterior horn cells, while remnant neurons were reduced in size. No other pathologic changes were identified. This case indicates that in severe infantile spinal muscular atrophy, relative sparing of the motor units with type II myofibers may occur. PMID- 1940136 TI - Benign familial neonatal convulsions are epileptic. AB - An infant with benign familial neonatal convulsions fortuitously had a clinical seizure during a routine EEG. The seizures had started on day 2 of life, and the EEG recording was performed on day 6. The EEG, although not complete, did show a simultaneous electrographic seizure. Our finding establishes that benign familial neonatal convulsions are indeed epileptic. PMID- 1940137 TI - Illustrated lecture by J. Ramsay Hunt. PMID- 1940138 TI - The epidemiology and natural history of infantile spasms. AB - Few population-based studies of infantile spasms have been done, and most reports have not included comparison groups. In spite of these limitations, this review attempts to summarize what is known about the distribution, etiology, and natural history of infantile spasms in populations; discusses the limitations of current data; and includes suggestions for further population-based research. Most estimates of the incidence of infantile spasms are between 0.25 and 0.42 per 1000 live births per year. Among children less than 10 years of age, the annual prevalence of infantile spasms is 0.14 to 0.19 per 1000. The peak age at onset of spasms is 4 to 6 months, and there appears to be a slight excess of male cases. The etiology of infantile spasms is unknown for 40% to 50% of affected children. Selected syndromes (eg, Aicardi syndrome, Down syndrome, etc) and inherited disorders (eg, tuberous sclerosis) may account for as many as one third of cases. Other factors, such as intrauterine infection, "birth injury," and head trauma have not been systematically evaluated, and thus, their contribution to the etiology of infantile spasms is uncertain. Areas for future etiologic research include controlled studies of immunologic factors and in utero and postnatal infections and further exploration of the interrelationship between infantile spasms and Lennox-Gastaut syndrome. PMID- 1940139 TI - The future of child neurology. PMID- 1940140 TI - Magnetic resonance imaging (MRI)--morphometric study. PMID- 1940141 TI - Catecholamine concentrations in plasma and organs of the fetal guinea pig during normoxemia, hypoxemia, and asphyxia. AB - To examine the responses of the sympatho-adrenal system to reduced oxygen supply we studied plasma and tissue concentrations of catecholamines during normoxemia, hypoxemia, and asphyxia in 22 fetal guinea pigs near term. Fetal blood was obtained by cardiopuncture in utero under ketamine/xylazine-anesthesia. Catecholamines were determined in plasma and tissue of 15 organs and 14 brain parts by HPLC-ECD. During normoxemia (SO2 54 +/- 4 (SE) %, pH 7.36 +/- 0.02, n = 5) plasma catecholamine levels were low (norepinephrine 447 +/- 53, epinephrine 42 +/- 12, dopamine 44 +/- 6 pg/ml). During hypoxemia (SO2 27 +/- 3%, pH 7.32 +/- 0.01, n = 6) and asphyxia (SO2 24 +/- 2%, pH 7.23 +/- 0.02, n = 11) tissue catecholamine concentrations changed with changing blood gases and with increasing plasma catecholamines. Norepinephrine concentrations increased in both skin and lung and decreased in liver, pancreas, and scalp; those of epinephrine increased in the heart, lung liver, and scalp and decreased in the adrenal. There were only minor changes in brain catecholamine concentrations except for a 50% reduction in dopamine in the caudate nucleus. Concentrations of dopamine catabolite 3,4-dihydroxyphenylacetic acid decreased in many brain parts, suggesting that cerebral catecholamine metabolism was affected by hypoxemia and asphyxia. We conclude that the sympatho-adrenal system of fetal guinea pigs near term is mature and that its stimulation by reduced fetal oxygen supply leads to changes in both plasma and tissue catecholamine concentrations. PMID- 1940143 TI - ECG waveform, short term heart rate variability and plasma catecholamine concentrations in response to hypoxia in intrauterine growth retarded guinea-pig fetuses. AB - After unilateral uterine artery ligation in midpregnancy twelve guinea-pig does were anesthetized at 63 days of gestation. The ST waveform of the fetal electrocardiogram and the short term heart rate variability were studied during normoxia and in response to acute hypoxia in growth retarded fetuses (n = 12, mean +/- SEM, 58.5 +/- 3.9 g) and their normal sized littermates (n = 12, 94.3 +/ 3.5 g). Hypoxia was induced by letting the doe breathe a low-oxygen gas mixture. After 10 min of hypoxia fetal blood was sampled by decapitation and blood gases, acid-base status and catecholamine concentrations were analyzed. The does responded to decrease in inspired oxygen concentration with changes in oxygen tension (13.8 +/- 0.8 to 4.3 +/- 0.2 kPa) and oxygen saturation (99.9 +/- 0.1% to 70.5 +/- 1.8%). Fetal blood gases and plasma catecholamine concentrations did not differ between the groups. In the growth retarded group standard bicarbonate was significantly lower compared to controls. The T/QRS ratio (the quotient between T wave height and QRS peak to peak amplitude) was normal and similar in both groups prior to the hypoxic period. In response to hypoxia T/QRS ratio increased in the normal sized group and T/QRS was correlated to carbon dioxide tension, oxygen saturation, pH, lactate, standard bicarbonate concentration, standard base excess and plasma noradrenaline concentration, respectively. The growth retarded fetuses presented a completely different pattern where 7 out of 12 fetuses showed a biphasic ST waveform during hypoxia with depression and downward sloping of the ST segment and negative T wave.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940142 TI - The blood supply to the heart and brain in the growth retarded guinea pig fetus. AB - Blood flow to the heart and brain of 31 control and 15 growth retarded (IUGR) guinea pig fetuses was measured between 60-64 days of pregnancy by the microsphere technique. The animals were anaesthetized with diazepam and pentobarbitone. Brain weight was reduced by 11% in IUGR fetuses from 2.61 +/- 0.03 to 2.33 +/- 0.05 g and heart weight by 39% from 0.42 +/- 0.01 to 0.25 +/- 0.01 g, compared to a decrease in body weight of 42% from 83.6 +/- 2.3 to 48.2 +/ 2.2 g. The myocardial blood flow of control animals was negatively correlated to arterial O2 content (r = 0.78, P less than 0.001) and arterial pH (r = 0.68, P less than 0.001). Brain blood flow was inversely correlated to arterial O2 content in control fetuses (r = 0.79, P less than 0.001). Eight regions of the brain were examined: cerebral hemispheres, caudate nucleus, hippocampus, thalamus + hypothalamus, cerebellum, pons, and medulla. Regional blood flows were significantly correlated to fetal oxygenation in the controls. Growth retarded fetuses were characterized by poor oxygenation (arterial O2 content less than or equal to 2.5 mM) and were frequently acidaemic (pH less than 7.20). No relation could be demonstrated between the myocardial or cerebral blood flows of IUGR fetuses and arterial O2 content or pH. It is concluded that growth retarded fetuses are unable to maintain O2 delivery to the brain and myocardium by increases in blood flow. Although O2 extraction could be increased to meet the O2 requirements of the heart, IUGR fetuses had a lower rate pressure product, suggesting a decline in myocardial O2 consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940144 TI - Effects of severe reduction in maternal placental blood flow on blood flow distribution in the sheep fetus. AB - To test the hypothesis that fetal lambs are able to maintain oxygen delivery to myocardial, brain and adrenal tissues during reduction in uterine blood flow to 25% of control, we performed experiments on five ewes and their fetuses. A snare occluder was placed around the maternal common hypogastric artery and catheters were placed for measurement of blood pressures, flows, blood gas tensions, pH and oxygen content. After a five day recovery period, control measurements were made. The snare occluder was then closed until the artery was fully occluded. The arterial occlusion caused uteroplacental blood flow to fall to 32 +/- 4% and maternal placental blood flow to fall to 25 +/- 3% of control values. This level of asphyxia was maintained for 19 +/- 3 minutes, when maternal and fetal blood flows were measured again. In response to occlusion, fetal ascending aortic PO2 fell from 21 +/- 2 (SEM) to 13 +/- 2 mmHg (P less than or equal to 0.01), oxygen content from 4.3 +/- 0.3 to 1.4 +/- 0.2 mM (P less than or equal to 0.01) and pH from 7.37 +/- 0.01 to 7.21 +/- 0.05 (P less than or equal to 0.01). PCO2 rose from 48 +/- 1 to 62 +/- 3 mmHg (P less than or equal to 0.01). Fetal arterial blood pressure increased from 51 +/- 3 to 61 +/- 3 mmHg (P less than or equal to 0.001) and heart rate decreased from 172 +/- 10 to 104 +/- 4 beats.min-1 (P less than or equal to 0.01). The heart, brain and adrenals showed vasodilation in response to the asphyxic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940145 TI - Cardiovascular responses to acute, severe haemorrhage in fetal sheep. AB - In adults, the responses to acute haemorrhage vary greatly depending on the amount of blood lost. While many studies have documented fetal responses to mild haemorrhage, fetal responses to severe haemorrhage are not known. In this study we examined the effect of acute, severe haemorrhage in fetal lambs. Despite the severity of haemorrhage, we found that mean arterial blood pressure was restored within 2 min, and heart rate was restored within 30 min. This restoration of blood pressure and heart rate was facilitated by an increase in peripheral vascular resistance mediated in part by secretion of catecholamines and plasma renin. In addition, about 40% of the shed blood volume was restored within 30 min by fluid from either the fetal interstitium or placenta. The PO2 of umbilical venous blood increased from 33 +/- 9 mmHg to 49 +/- 17 mmHg 2 min post haemorrhage, and to 47 +/- 15 mmHg 30 min post-haemorrhage. However, this increase was not sufficient to offset the fall in both haemoglobin concentration and umbilical-placental blood flow, so that oxygen delivery decreased from 21.1 +/- 5.5 ml/min per kg to 9.1 +/- 5.2 ml/min per kg 2 min post-haemorrhage, and 14.1 +/- 9.2 ml/min per kg 30 min post-haemorrhage. Because of this decrease in oxygen delivery, oxygen consumption fell and a metabolic acidemia ensued. Nevertheless, oxygen delivery to the heart and brain was maintained because hepatic vasoconstriction diverted more of the well oxygenated umbilical venous return through the ductus venosus. Although the fetus was able to tolerate acute loss of 40% of blood volume, larger volumes of haemorrhage resulted in fetal death. PMID- 1940146 TI - The response of small vessel endothelial cells from fetal rat lung to growth factors. AB - Small vessel pulmonary endothelial cells were obtained from rat fetal lung at day 20 of gestation, and were maintained in culture to passage three for study. Endothelial cells grown on a collagen matrix with Dulbecco's minimal essential medium: Ham's F12 medium (1:1, v/v) supplemented with 20 ml/l fetal bovine serum, bovine pituitary extract (50 mg/l), endothelial cell growth supplement (100 mg/l), hydrocortisone (1 mg/l) and an increased (10 mmol/l) magnesium concentration retained the characteristic endothelial cell marker factor VIII antigen during the third passage in culture. The factors responsible for small vessel growth in the developing fetal lung are unknown. To test the hypothesis that small vessel pulmonary endothelial cells would respond to autocrine or paracrine growth factors the effects of conditioned media from fetal lung endothelial cells, fibroblasts and pneumocytes from lungs of the same gestational age were studied in vitro. None of the tested conditioned media had any effect on endothelial cell DNA synthesis in the presence of 20 ml/l fetal bovine serum. Since no paracrine or autocrine effects of conditioned media were observed, the effect of other growth factors that could be derived from the circulation, or from storage sites in subcellular matrix, were studied for effect. When endothelial cells were studied in the presence of 20 ml/l fetal bovine serum and 100 mg/l endothelial cell growth supplement they had enhanced DNA synthesis in response to the progression-type growth factors insulin (5 mg/l), insulin-like growth factor-I and insulin-like growth factor-II (20 micrograms/l) and epidermal growth factor (10 micrograms/l). In the absence of serum or endothelial growth supplement endothelial cell DNA synthesis was enhanced by the competence-type growth factors acidic and basic fibroblastic growth factors at 100 micrograms/l and platelet derived growth factor at 10 micrograms/l. In the absence of exogenous competence-type growth factors neutralizing antibodies to basic fibroblast growth factor reduce DNA synthesis. Of various cytokines tested only interleukin-1 (1 x 10(3) U/l) and tumor necrosis factor (25 x 10(4) U/l) had an effect on endothelial cell DNA synthesis. Endothelial cell division during fetal lung development may be controlled by progression growth factors present in serum, and by either autocrine release of the competence factor basic fibroblast growth factor or paracrine release of platelet-derived growth factor by other cell types. PMID- 1940147 TI - Quantitative studies of the vasculature of the carotid body in fetal and newborn sheep. AB - Resetting of the hypoxic sensitivity of the carotid chemoreceptors from the fetal to the adult arterial PO2 range follows the rise in PO2 which occurs after birth. The mechanism of this resetting is unknown. To study whether it is accompanied by a change in the carotid body microvasculature, 2 pairs of carotid bodies from fetal sheep (145 days gestation) and 2 pairs from 7-8 days-old lambs were examined. The ratio of the area of small vessels (6-16 microns diameter) or of larger vessels (greater than 16 microns diameter) to the total area of individual lobules of the carotid body was measured, using a semi-automatic image analysis system. This quantified the number and total cross-sectional area of small vessels and of larger vessels in 20 sections of 5 microns thickness taken at random from 200-350 sections cut from each carotid body. When the carotid bodies of the fetus and neonate were compared, the neonates showed increases in the percentage of the lobule area occupied by both small and large vessels, but the difference was only significant in the case of the larger vessels. There was no difference in the ratio of the area occupied by smaller vessels to the extravascular area of the lobule. Our results do not support the idea that the post-natal resetting of chemoreceptor sensitivity from the fetal to the post natal range is accompanied by a change in the perfusion of the carotid body chemoreceptor cells. PMID- 1940148 TI - Arousal response to upper airway obstruction in young lambs: comparison of nasal and tracheal occlusion. AB - Experiments were done on seven lambs to determine if site of occlusion--nasal versus tracheal--influences the cardiopulmonary and arousal responses from sleep to upper airway obstruction. Each lamb was anesthetized and instrumented for sleep staging and measurements of heart rate and arterial hemoglobin oxygen saturation. A tracheostomy was also done and a fenestrated tracheostomy tube placed in the trachea. Prior to an experiment, A 5F balloon-tipped catheter was inserted through the decannulation cannula into the tracheostomy tube so that tracheal occlusions could be accomplished by inflating the balloon. In addition, a 5F balloon-tipped catheter was inserted into the inlet of a pre-formed silicone mask sealed to the animals snout with silicone rubber foam so that nasal occlusions could be accomplished by inflating the balloon. During an experiment, measurements were made in quiet sleep and in active sleep during control periods of tidal breathing and during experimental periods of nasal or tracheal occlusion. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred sooner following nasal occlusion than during tracheal occlusion in quiet sleep; 64 percent of arousals occurred within five seconds of nasal occlusion whereas only 14 percent of arousals occurred within five seconds of tracheal occlusion in quiet sleep. In addition, SaO2 and heart rate decreased more before arousal following tracheal occlusion than following nasal occlusion. However, there was not a significant effect of site of obstruction on time to arousal or the change in SaO2 before arousal in active sleep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940149 TI - Effects of altering umbilical flow and umbilical free fatty acid concentration on transfer of free fatty acids across the rabbit placenta. AB - The transfer of free fatty acids across the placenta perfused in situ was studied in anaesthetized rabbits in late gestation. In the first series of experiments, umbilical flow rate was varied between 0.6 and 4.0 ml/min in nine rabbits. Although increasing umbilical flow rate significantly decreased the free fatty acid concentration in the umbilical venous effluent (P = 0.0001), placental clearance of free fatty acids from the maternal circulation was not significantly changed by alterations in umbilical flow rate. In the second series of experiments, the materno-fetal free fatty acid concentration gradient was varied between + 1.58 mmol/l and -2.81 mmol/l in eight rabbits. There was a significant relationship between increasing materno-fetal gradient and increasing transfer of free fatty acids across the placenta (P less than 0.001). Moreover, net transfer of free fatty acids into the umbilical circulation was observed even with zero concentration gradient. Net transfer of free fatty acids from fetus to mother occurred when umbilical arterial free fatty acid concentration exceeded maternal arterial concentration by 1.3 mmol/l. PMID- 1940150 TI - Fever in young lambs: temperature, metabolic and cardiorespiratory responses to a small dose of bacterial pyrogen. AB - Experiments were done on ten lambs ranging in age from 15 to 25 days to define the temperature, metabolic and cardiorespiratory responses to intravenous administration of a small dose of bacterial pyrogen (SAE). Administration of SAE but not normal saline produced a short-lived fever of about 0.7 degrees C. The increase in body-core temperature was preceded by a surge in total body oxygen consumption and the onset of shivering which was influenced by behavioral state (ie, shivering was inhibited during active sleep). The increase in total body oxygen consumption was initially met by an increase in total body oxygen extraction and then by an increase in systemic oxygen delivery. Systemic arterial blood pressure did not change significantly during the febrile response; however, pulmonic arterial blood pressure increased significantly. Thus, our experiments provide new data on oxygen supply and demand during the development of fever and that shivering thermogenesis is inhibited in active sleep following the administration of bacterial pyrogen in young lambs. The influence of active sleep on the overall febrile response, and whether or not there is a shift from shivering thermogenesis to non-shivering thermogenesis remains to be determined. PMID- 1940151 TI - Influence of sympathetic innervation on the membrane electrical properties of neonatal rat cardiomyocytes in culture. AB - Co-cultures of rat ventricular myocytes and sympathetic neurons were established. Superior cervical ganglia and ventricles from newborn rats were enzymatically dissociated and plated in a culture dish. Experiments were done between the 3rd (when evidence of neuron-myocyte proximity arises) and the 5th day in culture (before the myocytes become confluent). Simultaneous intracellular recording from a cardiomyocyte and an attached neuron was done using conventional microelectrode techniques (resistance of 60-100 Mohm). The myocytes in co-culture were either quiescent or spontaneously contracting. The contracting cells were either latent pacemaker or ventricular-like myocytes. The action potential (AP) characteristics of cardiomyocytes in co-cultures were comparable to those recorded in cardiomyocytes in pure cultures. Sympathetic innervation of the cardiomyocytes in co-cultures was evidenced by stimulating the neuron and observing an increase in rate of beating in latent pacemaker myocytes (average increase of 19.4 +/- 4.6%). In quiescent cardiomyocytes, neural stimulation evoked a slow depolarization that can reach threshold and initiate APs in the cell. This response is similar to slow excitatory postsynaptic potentials (EPSPs) observed in other synapses. Slow ESPSs could also be recorded in spontaneous beating cells, made quiescent by nifedipine (1x10(-6)-1x10(-7) M). These results indicate that functional synaptic contacts are developed in co-culture of sympathetic neurons and cardiac myocytes, and slow EPSPs can be evoked in cardiomyocytes as well as in other excitable cells. The sympathetic innervation occurring in culture did not significantly modify the spontaneous AP characteristics of the cardiomyocytes. PMID- 1940152 TI - Identification of the hyperpolarization-activated inward current in young embryonic chick heart myocytes. AB - Whole-cell voltage-clamp experiments were performed to examine the underlying currents flowing during the pacemaker potential of spontaneously-beating embryonic chick ventricles. The holding potential was -30 mV. Long-duration (3 s) hyperpolarizing pulses were applied to -40 to -120 mV, in increments of 10 mV. A marked hyperpolarization-activated inward current (If) was produced. In cells from 3-day-old hearts, the threshold potential for the inward current was -50 to 60 mV. In 17-day-old cells, there was almost no If current. At -120 mV, the inward current was -93.8 +/- 6.3 pA (n = 5) in 3-day-old cells and -15.7 +/- 2.8 pA (n = 5) in 17-day-old cells. The average capacitances were 10.1 +/- 2.0 pF (n = 17) in 3-day-old cells, and 6.9 +/- 1.2 pF (n = 14) in 17-day-old cells. The reduction of If paralleled the decrease in spontaneous activity. In the presence of 3 mM CsCl, the inward current was blocked completely, and the tail current was reduced. In addition, 3 mM CsCl depressed the spontaneous action potentials and had a negative chronotropic effect. These results indicate that the hyperpolarization-activated inward If current exists in young embryonic chick heart cells, and decreases during development. This If current may contribute somewhat to the electrogenesis of the pacemaker potential. PMID- 1940153 TI - Dupuytren's disease among the Chinese in Taiwan. AB - A retrospective study was made of 41 cases of Dupuytren's disease observed from 1970 to 1988 at the Veterans General Hospital-Taipei, Taiwan. The patients' ages ranged from 49 to 78 years; 21 patients had only one hand involved; 20 patients showed bilateral involvement. Thirty-three of 35 diseased hands with contracture were treated by regional fasciectomy. A follow-up study was done in 32 hands. The operative results of 30 hands were rated as good (94%); 3 showed extension of the disease and 1 had evidence of recurrence. Treatment was not given to 26 hands without contracture; 14 of these showed no change in the lesions, 3 improved, and 6 were worse when seen on subsequent visits. Seventeen of 33 excised thickened palmar fasciae contained nodules. All histological sections of nodule-free specimens showed dense connective tissues. Based on the fibroblastic activity and the amount of collagen, three easily discernible features of the histological make-up of the nodules were found. PMID- 1940154 TI - Nodular fasciitis: a rapidly growing tumor of the hand. AB - Nodular fasciitis is an uncommon benign neoplasm infrequently seen in the hand. There are often difficulties in diagnosis of this tumor. It is usually surgically excised while it is still small. The patient described here had a large and aggressive tumor that ruptured through the skin of the hand and extended to the periosteum of the ring metacarpal. PMID- 1940156 TI - Tendon transfers in patients with cervical spinal cord injury. AB - Between 1983 and 1988, 32 patients with cervical spinal cord injuries underwent 124 upper limb tendon transfers during 85 procedures. Of the numerous surgical procedures that have been recommended for treatment of this condition, my experience indicates that the most successful are posterior deltoid-to-triceps transfer, restoration of finger flexion, and restoration of thumb opposition. Longitudinal incisions prove to be quite cosmetic. PMID- 1940155 TI - Reconstruction of finger and elbow function after complete avulsion of the brachial plexus. AB - Simultaneous reconstruction of elbow and finger function with free muscle and nerve transfers after complete avulsion of the brachial plexus (nerve roots C5 to T1) and its long-term results are presented. The basic procedure combined free or vascular pedicle latissimus dorsi muscle transfer with reinnervation by the spinal accessory nerve to obtain elbow and finger flexion, intercostal nerve transfer of the radial nerve to activate elbow and wrist extensors, and suture of the supraclavicular nerve or intercostal sensory rami to the median nerve to restore hand sensibility. Six patients had some or all of these procedures. Postoperative follow-up ranged from 2 to 5 years. Elbow function was restored completely, and some finger flexion was achieved in all cases, although a dynamic splint was necessary to straighten the digits. Patients have continued to improve in grasp power and finger control. This procedure appears to be promising for the restoration of basic hand function in severely handicapped patients. PMID- 1940157 TI - Creation of an opposable small finger by muscle transfer. AB - We present a case of a child born with metacarpal synostosis of the index, long, and ring fingers associated with a simple syndactyly of the small finger and an absent thumb. At age 7 months, a syndactyly release with skin grafting to the small finger was accomplished so that it became the new thumb. At age 4 years, one of the muscles on the radical border of the hand was transferred to the small finger to act as an opposition transfer. At follow-up, the transfer contracted well and the functional capability of the hand was improved. This operation will not often be used but should be considered for the occasional patient with congenital anomalies. PMID- 1940158 TI - Surgical correction of claw fingers in Hansen's disease by palmar plate shortening and pulley advancement. AB - A simple technique has been used to correct the clawing of fingers in patients with Hansen's disease. The distal part of the palmar plate is excised and the remaining portion is advanced and sutured with a single horizontal mattress suture to prevent hyperextension of the metacarpophalangeal joint. A pulley advancement is also done. One hundred five claw hands were corrected in 99 patients from December 1985 to September 1988. Follow-up period varied from 6 months to 3 1/2 years. The results were assessed for correction of deformity, power grip, motion, and function. Out of 94 hands that were followed up after operation, power grip remained static in most cases. Correction of deformity was satisfactory in 85 hands, motion and function of the fingers were satisfactory in 63 hands, and correction of the clawing was statistically significant in two fingers (p less than 0.01). PMID- 1940159 TI - The abductor digiti minimi muscle flap: an adjunct in the treatment of metacarpal osteomyelitis. AB - The abductor digiti minimi muscle has a constant 1 to 1.5 cm neurovascular pedicle that arises from the ulnar artery and nerve within Guyon's canal. We have successfully used the abductor digiti minimi as a pedicle transfer as an adjunct in the treatment of chronic osteomyelitis of the small and ring finger metacarpal shafts. PMID- 1940160 TI - Solitary osseous sarcoidosis in a finger. AB - Sarcoidosis confined to a single bone in a patient with chronic systemic sarcoidosis and seen as a soft tissue mass is exceedingly rare. The combination of lytic and sclerotic changes within one bone has not been previously reported. PMID- 1940161 TI - Management of potentially infected complex hand injuries. AB - Fifteen patients with contaminated, and thus potentially infected, hand injuries were treated. All had segmental bone loss: six metacarpals, three proximal phalanges, three middle phalanges, and three joint injuries. The treatment was based on the simultaneous primary application of external minifixators and antibiotic-loaded bone cement beads and completed by early bone grafting. This external fixation and internal antibiotic treatment has synergic effect both mechanically and biologically. Thus potentially infected fresh injuries were treated in exactly the same way as an established osteomyelitis. Although there were a few minor wound problems and superficial pin tract infections, there were no deep infections, and no bone grafts were lost. All of the patients were grafted with autologous bone taken from the ilium within 7 to 8 days. Rehabilitation time was markedly decreased by this method, and all of the patients returned to work within 8 months. PMID- 1940162 TI - Pathologic fractures: a complication of microparticulate synovitis. AB - We report seven cases of pathologic fracture in adult patients that were seen an average of 5 years (range from 33 to 114 months) after silicone wrist (three) and trapezial (four) arthroplasty. All patients had initially done well after their operation. At return, all had radiographic evidence of generalized implant and intramedullary bone destruction, the latter always including endosteal scalloping and widening from cortical resorption. These radiographic changes may be less striking than the discrete osteolytic lesions seen after degeneration of carpal implants. Our patients represent examples of pathologic fracture as the end stage of untreated microparticulate synovitis, a consequence of prosthetic wear. Our experience suggests that careful and continuous follow-up justified after insertion of stemmed silicone implants, and that patients should be informed of the potential late complications of this procedure, including pathologic fracture. PMID- 1940163 TI - Pilon fractures of the proximal interphalangeal joint. AB - A pilon fracture is an uncommon intraarticular fracture of the proximal interphalangeal (PIP) joint resulting in comminution, central depression, and splay, sagittally and coronally, of the articular surface of the base of the middle phalanx. This study reviews three treatment methods and results in 20 patients. Injury was produced by an axial load and occurred primarily to the ulnar digits. Clinical and radiographic follow-up averaged 25 months. Treatment was divided into three categories: splint (four patients), skeletal traction through the middle phalanx (seven patients), and open reduction with Kirschner pins (nine patients). Anatomic restoration of PIP articular contour was not achieved, regardless of technique. No patient regained full mobility at either interphalangeal joint. Treatment by immobilization is undesirable. Open reduction should be approached cautiously and may result in significant complications. Skeletal traction is safe and gives results that are radiographically and clinically comparable to those achieved with open reduction. PMID- 1940164 TI - Stress relaxation of a peripheral nerve. AB - This study determines the change in tension after an acute nerve lengthening, as would occur in peripheral nerve repair. Stress relaxation, a viscoelastic property, was studied with the use of 24 rabbit tibial nerves. The nerves were divided into three groups and were stretched 6%, 9%, or 12% beyond their original resting length. The mean 1-hour stress relaxations for the three groups were 48%, 34%, and 34%, respectively. Nerve stress relaxation was significantly greater at 6% strain than at 9% or 12% strain. These biomechanical findings have important clinical implications for nerve-stretch injury and for nerve repair. PMID- 1940166 TI - Sebaceous gland carcinoma of the finger. AB - We report a patient with sebaceous gland carcinoma of the finger. Sebaceous gland carcinomas located outside the ocular adnexa are rare, with fewer than 100 cases documented to date. The majority of these arise in the head and neck where sebaceous glands are plentiful. Because this tumor shows no pathognomonic characteristics, accurate histologic evaluation is essential to its diagnosis. Local excision may not be adequate treatment for a sebaceous gland carcinoma of the digit. Ray amputation was the treatment of choice for this patient. PMID- 1940165 TI - Sensory neural loop of the median nerve at the carpal tunnel. AB - This article discusses a sensory neural loop on the radial aspect of the median nerve in the palm. The surgeon should be aware of this anomaly when the transverse carpal ligament is divided to approach the structures contained in the carpal canal. PMID- 1940167 TI - Neurofibrosarcomas of the upper extremity. AB - A retrospective review of all malignant hand tumors seen at the University of Michigan from 1950 to 1987 demonstrated six biopsy-proven cases of neurofibrosarcoma involving the upper extremity. There were four male and two female patients; average age at presentation was 37 years and ages ranged from 15 to 63 years. All patients had a history of von Recklinghausen's disease. Three patients were seen initially with painful enlarging masses, one with a painful mass with a neurological deficit, and two with painless enlarging masses. Three patients had radical excisions requiring upper extremity or forequarter amputation, and three patients received limited or no surgical treatment. Five patients died of metastases an average of 3 years after diagnosis. One patient remains alive 18 years after upper extremity amputation despite an early local recurrence. Early diagnosis and radical surgical excision offer the best chance of long-term survival from this highly lethal cancer. PMID- 1940168 TI - Fibrosarcoma of metacarpal treated by combined therapy and immediate reconstruction with vascularized bone graft. AB - Fibrosarcomas of the bones of the hand are very rare entities. We present a case of low-grade fibrosarcoma of the left third metacarpal that was successfully treated by preoperative intraarterial chemotherapy, wide local excision, and immediate reconstruction with a vascularized bone graft from the ipsilateral radius. Excellent hand function has been preserved and the patient remains free of recurrence 5 years after presentation. PMID- 1940169 TI - Digital ranges of motion: normal values in young adults. AB - Analysis of the range of motion of fingers was done in young (eighteen to thirty five year old) adult volunteers with no history of previous injury to their hands. The data show that there are slight differences between the individual digits. Notably, metacarpophalangeal flexion and total active motion increase linearly in proceeding from the index to the small finger. There were also minor differences in comparing sexes. Women have greater extension at the metacarpophalangeal joint in both active and passive motion and have a greater total active motion at all digits as a result. A significant tenodesis effect was found at the distal interphalangeal joint in normal subjects. No differences were found that could be attributable to handedness. PMID- 1940170 TI - Measurements of carpal bone angles on lateral wrist radiographs. AB - Measurements of carpal bone angles on lateral wrist radiographs can be of assistance in the diagnostic evaluation of wrist malalignment. A series of 75 normal wrists was examined by use of a standardized radiographic technique. The normal carpal bone angles were determined using the bone axes with the least observer variability (mean and range): radiolunate, -1.02 (-10 to 12), radioscaphoid, 51.80 (35 to 65), and scapholunate, 50.77 (36 to 66). Normal mean values and ranges for intercarpal bone angles may be of assistance in the diagnostic evaluation of ligamentous injury to the wrist. PMID- 1940171 TI - Observer variability in measurements of carpal bone angles on lateral wrist radiographs. AB - Determinations of carpal bone angles are used in the clinical evaluation of carpal malalignment. Eleven frequently referred radiological measures in lateral projection of the wrists in 23 wrists were assessed using different definitions of axes. Interobserver- and intraobserver variations were calculated. The standard deviation of the interobserver variation ranged from 2.60 degrees to 18.15 degrees, and the intraobserver variation from 1.89 degrees to 4.66 degrees depending on the angles measured. The use of three angles for the least observer variability in assessment of carpal alignment is recommended. These angles were defined from the following carpal bone axes: radius, the line through the center of the medullary canal at 2 cm and 5 cm proximal to the radiocarpal joint; lunate, the line perpendicular to the tangent of the two distal poles; scaphoid, the tangent of the palmar proximal and distal margins, and capitate, the tangent of the dorsal margin of the diaphysis of the third metacarpal bone (substitute axis). PMID- 1940172 TI - Computed analyses of the pathomechanics of scaphoid waist nonunions. AB - The computed tomography scans of both the injured and the normal wrists of nine patients with a scaphoid nonunion of 5 to 120 months' duration were used to create three-dimensional computer models. When the computer images of the normal and the contralateral fractured scaphoids were superimposed, it was possible to calculate the volume of bone that was lost as a result of the injury and its failure to heal, as well as the angular relationship of the fracture components to one another. The amount of the scaphoid bone that was lost varied from 6% to 15% of bone volume and did not show a linear correlation with the duration of the nonunion. The configuration of the missing bone was consistent and exhibited a prismatic shape whose base is quadrilateral and faces palmarly. The proximal scaphoid fracture component is extended, radially deviated, and supinated in relation to its distal fracture component. The consistent fracture deformity and the configuration of the bony defect in the scaphoid waist nonunions should be helpful in the understanding and treatment of the condition. PMID- 1940173 TI - Biomechanical comparison of fixation devices in experimental scaphoid osteotomies. AB - This study determined the force, bending rigidity, and bending moment at failure of three types of internal fixation systems for the scaphoid bone. A pair of parallel, 0.045-inch Kirschner wires were compared on a paired, bilateral basis with either a Herbert screw or a 3.5 millimeter cannulated screw in repairing a transverse waist osteotomy in cadaver scaphoids. The mean values at failure of the Herbert screw and the cannulated screw versus the paired, parallel Kirschner wires for force (65 N and 77 N versus 23.7 N), rigidity (0.47 Nm2 and 0.54 Nm2 versus 0.16 Nm2) and bending (0.98 Nm and 1.15 Nm versus 0.36 Nm) were approximately three times greater. These differences were statistically significant when compared on a paired basis. This experiment demonstrates that the Herbert screw and cannulated screw are significantly stronger in resisting bending forces than paired, parallel Kirschner wires. PMID- 1940174 TI - Treatment of nonunions of the scaphoid with the Ender compression blade plate system. AB - A relatively high failure rate is associated with bone grafting with or without screw fixation in scaphoid nonunions. Complicating factors include avascular necrosis, cystic degeneration, and osseous size discrepancy or compromise. The Ender blade plate is suitable for adding stability in these cases, in spite of the necessity for late removal and the possibility of articular impingement. Twenty patients were treated with this technique. Nine of these patients had had previous unsuccessful attempts at nonunion repair. Nineteen had satisfactory results, but one had a persistent nonunion. The use of the Ender blade plate system is applicable for treatment of these difficult cases that are not ideally suited to compression screw fixation. PMID- 1940175 TI - Clinical application of sapphire pins as an internal fixation device for the upper extremity. AB - Since June 1980, sapphire pins (monocrystalline alumina ceramic pins) have been used in 22 patients as an internal fixation device for hand and elbow problems. In our follow-up studies, good bone healing was observed in all cases except for one delayed union in a fracture of the diaphysis of the proximal phalanx. Radiographs showed no pin migration or osteolytic reaction around the pins. We therefore conclude that our device and its insertion technique can be successfully applied to intraarticular fractures and fractures in the vicinity of the joint. PMID- 1940176 TI - Use of the Ilizarov technique to treat radial nonunion with physeal arrest. PMID- 1940177 TI - Callotasis lengthening in the upper extremity: indications, techniques, and pitfalls. AB - Bone lengthening through callotasis has been performed in 12 bones of the upper extremity in eight patients. Diagnoses included congenital amputations, phocomelia, radial agenesis, traumatic amputations, and infected fracture with bone loss. Nine of the 12 procedures resulted in complete consolidation of the transport gap with new bone without need for bone graft. One patient died of unrelated illness before completion of treatment but demonstrated early consolidation of the gap. In two cases bone graft was required. Complications included one superficial pin tract infection and one case of premature cessation of lengthening because of hand deviation. Early experience with this technique indicates that it is effective in the management of bone defects in the upper extremity. It appears that in most cases a half-frame lengthening device, rather than a more complex circular frame, can be used in the non-weight-bearing upper extremity. Adequate control of the distal segment, appropriate choice of location for corticotomy, and gentle handling of the bone and periosteum can improve results and minimize complications. PMID- 1940178 TI - Reconstruction of the humerus by soft tissue distraction and vascularized fibula transfer. AB - We report a case of reconstruction of the humeral shaft by soft tissue lengthening according to the method of Ilizarov, followed by skeletal reconstruction with a vascularized fibular graft. Skeletal union and initiation of functional activity were achieved within 4 months. Lengthening of the soft tissue and the vascular tree by slow distraction did not compromise the subsequent reconstructive microsurgical procedure. PMID- 1940179 TI - The management of trigger thumb in children. AB - Trigger thumb in children is an uncommon condition. We reviewed 41 patients with 53 trigger thumbs. Although the current accepted approach to the treatment of congenital trigger thumbs is a prolonged period of observation, our findings indicate that all of our patients eventually required surgical release of the flexor pollicis longus tendon. Waiting 3 years before a surgical release was done did not affect the surgical result. PMID- 1940180 TI - Correction of constriction rings. AB - A refinement in the correction of deep and shallow constriction rings, in which subcutaneous fat and fascial flaps are advanced into the defect to prevent recurrent contour deformities, is presented. A straight-line dorsal closure is preferred, with Z-plasties placed along the side of the digits, forearm, or arm. Long-term follow-up is presented in 58 patients with 116 constriction rings corrected by either traditional serial Z-plasties of skin (n = 61 rings) or this new method of contour correction (n = 55 rings). Specific correction of soft tissue is recommended when tissue is available. PMID- 1940181 TI - "Hand complications in children from digital sucking". PMID- 1940182 TI - "Transthecal digital block: flexor tendon sheath used for anaesthetic infusion". PMID- 1940183 TI - Gastroduodenal mucosal injury--acute and chronic: pathways, mediators, and mechanisms. AB - This review provides evidence that gastroduodenal mucosal injury is a complex process because of the heterogenous structure and multiple functions of the gut. The action of exogenous etiologic agents is usually mediated in part or amplified by endogenous mediators that very often exert biphasic, i.e., damaging and protective, effects. The pathogenetic pathways involved are direct/indirect chemical injury, vascular damage and its consequences, and acute or chronic inflammatory processes following infectious, chemical, or ischemic injury. The role of oxygen, free radicals, calcium, and proteases as well as the components and forms of gastroduodenal injury, e.g., reversible and irreversible cell injury, tissue necrosis, and acute and chronic inflammation, are also briefly discussed. PMID- 1940184 TI - Role of epidermal growth factor in protection and repair of gastric mucosal injury. AB - A role of epidermal growth factor (EGF) in protection and repair of gastric mucosal injury caused by p.o. administration of 0.6 N HCl was investigated in male Wistar rats. Previous to the study on the role of EGF in gastric mucosal protection and repair, changes of gastric mucosal EGF level was determined sequentially by RIA for 180 min after treatment with 0.6 N HCl and intraperitoneal injection of recombinant hEGF. Concentration of incorporated hEGF into the gastric mucosa reached the peak level at 30 min after injection of hEGF. On the other hand, the gastric endogenous EGF level fell remarkably immediately after treatment with 0.6 N HCl. Successively, an association with the mucosal levels of incorporated hEGF and gastric ulcer indices was investigated in the rats in which hEGF was injected intraperitoneally 30 min prior to or at the same time as oral administration of 0.6 N HCl. In conclusion, pretreatment with hEGF protected significantly against gastric mucosal injury with 0.6 N HCl, whereas simultaneous administration of hEGF could not protect against mucosal injury but indicated possible stimulation of the repair process from acute gastric mucosal damage. PMID- 1940185 TI - Expression of epidermal growth factor receptor in rat gastric oxyntic mucosa. AB - Epidermal growth factor (EGF) is a mitogenic polypeptide that inhibits gastric acid secretion, protects the gastric mucosa against acute injury, and accelerates ulcer healing. In the present study we demonstrated immunohistochemically, using two different techniques, localization of EGF receptors in normal rat gastric oxyntic mucosa: in proliferative zone cells and in some parietal cells. It is likely that these cells represent the major targets for the EGF [and transforming growth factor alpha (TGF-alpha) which shares a common receptor with EGF] actions, stimulating cell proliferation and inhibiting acid secretion. PMID- 1940186 TI - Helicobacter pylori: current perspectives. AB - Within the past decade, there has been an explosion of investigative activity and publications about Helicobacter pylori (H. pylori). Its role in gastroduodenal disease is becoming greater with definite etiologic association in chronic type B gastritis and a probable role in duodenal ulcer, a probable role in gastric ulcer, and possibly a factor in the development of interstitial type gastric carcinoma. Epidemiologic studies have shown H. pylori to be worldwide in distribution with higher prevalence rates and earlier initial infection rates in developing countries compared with industrialized nations. Person-to-person transmission appears to occur via the fecal-oral route. Pathogenesis of H. pylori associated diseases remains unclear. We are, however, gaining insights into the role that H. pylori extracellular products play in damage to mucin and gastric epithelial cells as well as other gastroduodenal physiologic processes. Antimicrobial treatment, when effective, produces remission of mucosal pathologic changes and reduces duodenal recurrence rates. A major as yet unsolved problem is that there is no completely effective treatment regimen that consistently eradicates H. pylori in infected patients. Concepts of pathogenesis and future directions of research are discussed. PMID- 1940187 TI - Evaluation of peptic ulcer healing with a highly magnifying endoscope: potential prognostic and therapeutic implications. AB - Gastric and duodenal ulcer healing and scarring were evaluated with a highly magnifying endoscope. The appearance of scar was classified into three types: Sa, with a depression at the center; Sb, with a pattern of regenerated mucosa reaching the center; and Sc, with a uniform pattern throughout. The relationship between regenerative mucosal patterns and histologic findings of biopsy specimens was investigated in 58 patients with gastric ulcer. Mucosal regeneration was sufficient in 26.7% of patients with Sa pattern, 79.2% of patients with Sb pattern, and 100% with Sc pattern. From prospective endoscopic follow-up observations, the relationship between endoscopic findings of ulcer scars and ulcer relapses was investigated in 80 patients with gastric ulcer and 56 patients with duodenal ulcer. As a result, patients who completed the cycle of ulcer healing from Sa pattern through Sb to Sc patterns had rarely relapse. In contrast, patients with a Sa pattern of mucosal scar showed a high rate of recurrence: 88.8% for gastric ulcer, and 88.0% for duodenal ulcer. Our method of evaluation of gastric and duodenal ulcer healing with a highly magnifying endoscope may have important prognostic and therapeutic implications. It may indicate a population of patients (with Sa scarring pattern) with a high risk of ulcer recurrence and therefore requiring prolonged prophylactic treatment. PMID- 1940188 TI - Morphologic and ultrastructural effects of Maalox TC on human gastric and duodenal mucosa. AB - Prostaglandins (PGs) and aluminum-containing antacids (Al.AAs) are effective in preventing gastric and duodenal lesions induced by neutralizing agents. The efficacy of Al.AAs is thought to be due to neutralizing properties and to stimulation of endogenous PGs synthesis. Liquid Maalox has the same effect as cimetidine 400 mg on postprandial duodenal acid load. In numerous prospective studies, Al.AAs have been shown to be as effective as cimetidine in the short term treatment of duodenal ulcer (DU). Maalox TC at a dosage of 3 tablets b.i.d. provides an effective method for preventing DU relapse. Its effect is similar to that of nighttime cimetidine. Meta-analysis of prospective trials suggests that Al.AAs prevent stress ulcers more effectively than does cimetidine. It has been suggested that Al.AA acts by inducing surface epithelial cell disruption. Al induced mucosal protection could be caused by a stimulated release of endogenous PGs, induced by Al microcrystal penetration of cells. In a recent study, we showed that small amounts of Al were absorbed by human gastric mucosa and accumulated in lysosomes; however, we did not observe any histological or ultrastructural lesions of the gastric mucosa. Prostaglandins (enprostil, misoprostol, and rioprostil) are as effective as cimetidine, but less effective than ranitidine, in healing DU. Enprostil and rioprostil have been shown to be as effective as ranitidine in treating gastric ulcer (GU). Moreover, enprostil inhibits postprandial gastrin release, whereas H2-blockers increase gastrin levels. Coadministration of misoprostol with aspirin is highly effective in healing aspirin-induced gastroduodenal lesions. Moreover, cotreatment with misoprostol was associated with a marked decrease in GU in patients with osteoarthritis receiving NSAIDs chronically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940189 TI - Low-dose antacids and nonsteroidal anti-inflammatory drug-induced gastropathy in humans. AB - Gastroduodenal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) is common. As yet, the ideal means to prevent NSAID-related mucosal injury remains controversial. Antacids are effective agents in treating gastric and duodenal ulcers unrelated to NSAIDs. The aim of this study was to assess the ability of a low-dose antacid to prevent NSAID injury in humans. Fifty healthy human volunteers were studied using a randomized, double-blind, placebo controlled, crossover design. After initial endoscopy, subjects were randomized to either Maalox TC (1 tablet q.i.d., acid neutralizing capacity of 104 mEq/day) or identical placebo while receiving 500 mg of naproxen b.i.d. for 21 days. After this period, a second endoscopy was performed to count antral and duodenal erosions and to evaluate symptoms and compliance with study medications. A 21-day washout period ensued, followed by a third endoscopy to insure a return to endoscopically normal mucosa. Subjects then crossed over into the alternate treatment arm for a further 21 days, followed by a fourth endoscopy to assess erosions. Forty subjects completed the study. Subjects receiving Maalox TC developed a significantly greater number of gastric erosions than did those on placebo. While this result was unforeseen, it is supported by statistical analysis and may have clinical relevance in regard to short-term NSAID therapy. PMID- 1940191 TI - Mechanisms of mucosal protective and healing action of antacids and other topically active agents. Facts, hypotheses, and speculations. PMID- 1940192 TI - Increased susceptibility of the portal hypertensive gastric mucosa to damage. AB - Portal hypertensive gastropathy has recently been recognized as a unique entity distinct from other gastropathies involving the normotensive gastric mucosa. To delineate the pathophysiology of this disorder, we developed a rat model of portal hypertension using two-staged portal vein ligation. In this model, features of the portal hypertensive mucosa include increased luminal hydrogen ion loss, reduced electronegativity of potential difference, and increased submucosal edema. Ultrastructurally, the portal hypertensive gastric mucosa has marked endothelial hypertrophy of capillaries resulting in prominent compromise of microvascular lumina. Combined with the submucosal edema, the microvasculopathy results in reduced oxygenation of the surface gastric mucosa. This is associated with diminished prostaglandin production, which impairs gastric mucosal protection in portal hypertension. These observations are strengthened by experiments that demonstrated significantly increased gastric mucosal damage by alcohol, bile acids, aspirin, and shock/reperfusion in portal hypertensive rats compared to normotensive sham-operated controls. Many of our experimental findings have been confirmed clinically; however, much more research in this area is clearly needed. PMID- 1940190 TI - Duodenal ulcer therapy with low-dose antacids: a multicenter trial. AB - One hundred outpatients with endoscopically verified duodenal ulcer were treated in a double-blind, randomized, multicenter trial with either low-dose antacid (AA, Supralox, 1 tablet three times a day 1 h a.c. and 2 tablets at bedtime, with acid binding capacity of 225 mEq) or misoprostol (MS, Cytotec, 400 micrograms p.o. b.i.d.). Patients were treated up to 4 weeks and underwent endoscopic and clinical evaluation at 2 and 4 weeks. Clinical symptoms were recorded at the beginning and at 2 and 4 weeks. Ninety-eight patients completed the study. After 4 weeks of treatment, the healing rate in the AA group was 79.6% compared with 74.4% in the MS group. The difference in healing rates between these two groups was statistically not significant. The effect on clinical symptoms assessed as percentage improvement during the therapy was similar under both medications. However, the relief of night pain was significantly higher during the first 2 weeks of AA therapy. The side effects of both treatments were minimal, with a higher rate of side effects (especially diarrhea) in the MS group. Thus, a low dose antacid tablet regimen is safe and effective therapy for duodenal ulcer patients. PMID- 1940193 TI - Assessment of mucus glycoprotein erosion by measurement of sialic acid in gastric secretions: pathophysiologic and therapeutic aspects. AB - The quantification of mucus glycoproteins (GPs) faces paramount difficulties in terms of methods and interpretation. Mucus glycoprotein erosion, however, might be quantified in gastric juice by measurement of GP-bound sialic acid. Basal sialic acid content was low in normal healthy subjects (N) and in nonulcer dyspepsia (NUD) patients. They were five to six times higher in duodenal ulcer (DU), or more in Zollinger-Ellison patients. Pentagastrin stimulation induced a five- to sixfold rise in N and NUD patients although it did not affect DU patient sialic acid contents. Relationships between sialic acid content and pepsin output in DU indicate that pepsin exerts a variable mucolytic activity depending on disease evolution. In addition to pepsin, duodenogastric reflux exerts a potent mucolytic effect. Therapeutically, highly selective vagotomy without recurrent ulcer markedly reduced mucus erosion. The reduction of mucus erosion by protective drugs has been observed in some cases but in other cases sialic acid measurement did not allow to verify a protective effect. Adherent mucus analysis by high-performance liquid chromatography (HPLC) should allow one to appreciate GP fractions qualitatively. Combination of both methods should allow further determination of the mucus protective role, simultaneously investigating the adherent mucus quality and eroded GPs. PMID- 1940194 TI - Gastric cytoprotection by ornoprostil, a PGE1 analogue, in human subjects. AB - Ornoprostil, a methyl derivative of PGE1 developed in Japan, was tested for its effect on gastric mucosal damage caused by ethanol in human subjects. Sixteen healthy volunteers were given either ornoprostil or a placebo, followed by 20 ml of 70% ethanol instilled into the gastric antral mucosa. Fifteen minutes later, visible mucosal lesions were evaluated endoscopically. The biopsy specimens were obtained from mucosa that had been exposed to ethanol but looked normal. The specimens were assessed by light microscopy and scanning electron microscopy. The gross mucosal damage demonstrated endoscopically was significantly less (p less than 0.05) in the subjects receiving ornoprostil than those receiving placebo. Hyperemia and hemorrhage in the mucosa were also significantly less (p less than 0.05) in the subjects given ornoprostil pretreatment. Ornoprostil, however, failed to prevent the disruption of surface epithelial cells as assessed by scanning electron microscopy. These data suggest that ornoprostil protects gastric mucosa against damage caused by concentrated ethanol. PMID- 1940195 TI - Repair and healing of established gastric mucosal injury. AB - Superficial injury of the gastric mucosa, such as occurs after ethanol or aspirin ingestion, is usually resurfaced in 1 or 2 h. This is accomplished by rapid migration of surface mucous cells to cover the defect, followed by a later increase in cellular proliferation to restore the pits to their original length. This rapid restitution has been documented with electron microscopy, and is also reflected in the speedy return to baseline of the transmucosal potential difference and ionic barrier function after superficial injury. Deeper mucosal injury--which occurs focally after injury by aspirin, other NSAIDs, and restraint stress--is evident as macroscopically visible erosions. These heal more slowly, and are resurfaced after several hours with apparently undifferentiated cells. These are probably derived from surviving surface mucous cells that rapidly dedifferentiate. Cell proliferation peaks after about 12 h, but too late to contribute to the resurfacing process. Specialized cells reappear 1 or 2 days later, and glandular remodeling is needed in the deeper lesions. Ulcers heal by processes analogous to the deeper erosions, but the time needed is much longer (weeks). Additional tasks are the re-formation of the muscularis mucosae, and the creation of pits and glands from the initially single sheet of migrating cells. PMID- 1940196 TI - Epithelial renewal in protection and repair of gastroduodenal mucosa. AB - The constant, rapid renewal of the gastroduodenal epithelium is an important mechanism of mucosal protection because it maintains the functional integrity of the epithelium. It also is necessary for the repair of mucosal injury. Aspirin, indomethacin, and ethanol all have been shown to stimulate epithelial proliferation in the experimental setting. The stimulatory effects of these agents may be a compensatory reaction to mild injury and may contribute to the process of mucosal adaptation. On the other hand, corticosteroids, physiologic stress, and smoking appear to depress epithelial proliferation, which could render the mucosa susceptible to the effects of other ulcerogens as well as retard the healing of existing mucosal lesions. Epithelial proliferation in mucosa adjacent to active duodenal ulcers as well as from nonulcerated duodenitis is increased when compared to normal-appearing mucosa. This stimulation of epithelial proliferation may be caused by inflammation; it is not known whether ulcer patients have a defect in epithelial proliferation that precedes ulceration. Although prostaglandins (PGs) protect ulceration. Although prostaglandins (PGs) protect the gastroduodenal mucosa, the weight of evidence indicates that PGs do not have a primary effect on epithelial proliferation but rather retard senescence and loss of epithelial cells. The result is thickening of the mucosa, which may contribute to the protective effects of PGs. Ulcerogenic agents or conditions may either depress epithelial proliferation, which predisposes to ulceration or the ulcerogenic effects of other ulcerogens, or result in a hyperproliferative response, which may contribute to the process of mucosal adaptation and protection. PMID- 1940197 TI - Effects of prostaglandins on hydrocortisone-induced delayed healing of chronic gastric ulcers in the rat. AB - We have previously shown that chronic steroid administration delays the healing of experimental gastric ulcers in rats. This study was designed to test the beneficial effects of 16,16-dimethylprostaglandin E2 or TRY-200, a stable prostaglandin I2 analogue, on the delayed healing by hydrocortisone (HC) of chronic gastric ulcers in rats. Chronic gastric ulcers were produced in male Wistar rats, weighing 180 g, by serosal application of 100% acetic acid. The rats were randomly divided into six groups: (1) saline, (2) saline, HC-treated, (3) 10 micrograms/kg of 16,16-dimethylprostaglandin E2, (4) TRY-200, a stable prostaglandin I2 analogue, at 5 micrograms/kg, or (5) 10 micrograms/kg, or (6) 30 micrograms/kg. All rats, except for control, were given daily intraperitoneal injection of 2.5 mg/kg of HC sodium phosphate. Tested drugs were administered intragastrically twice a day for 2 weeks. Rats were killed 14 days later and ulcer size was measured. Chronic administration of HC sodium phosphate resulted in a significant delay of ulcer healing induced by acetic acid. Treatment with TRY-200 at 10 or 30 micrograms/kg abolished the deleterious effect of steroids, whereas 16,16-dimethylprostaglandin E2 had no effect. These results indicate that prostaglandin I2 is more effective than prostaglandin E2 in reversing the delayed healing by steroids of chronic gastric ulcers in the rat. PMID- 1940198 TI - Gastric mucosal repair in vitro. AB - We tested whether cultured gastric mucosal cells would be suitable to study the two major steps of repair: restitution and proliferation. Preparations of freshly isolated epithelial cells of guinea pig gastric mucosa were used for the studies. The cells attached to Petri dishes within 10 h and formed monolayers after 48-72 h. Electron microscopy showed that each cell type was able to form lamellipodia (i.e., cell protrusions) during restitution in vivo. When monolayers were wounded with a razor blade, most cells at the edge of damage died within a few minutes, but some recovered from injury. Later, intact cells migrated from the edge into the denuded zone and restored the monolayer within 24-48 h. An increased number of cells near the edge started to synthesize DNA. In conclusion, this model allows one to study in vitro both aspects of mucosal repair. PMID- 1940199 TI - Role of prostaglandins in gastroduodenal mucosal protection. AB - Prostaglandins protect the gastroduodenal mucosa from damage caused by diverse noxious agents. This protection (cytoprotection) occurs under experimental conditions where intraluminal acid is required for maximal expression of damage (e.g., stress, aspirin, and bile acids), as well as where damage occurs irrespective of the presence of acid (e.g., 100% ethanol, boiling water, and lye). Prostaglandins stimulate several factors felt to be important in maintaining normal mucosal integrity, such as mucus synthesis and secretion, mucosal bicarbonate secretion, mucosal blood flow, and cellular repair. Inhibition of the prostaglandin synthetic enzyme, cyclooxygenase, by nonsteroidal anti-inflammatory drugs (NSAIDs), is associated with increased gastroduodenal mucosal damage and ulceration. This damage is primarily the result of decreased tissue levels of prostaglandins, but may also be due to direct NSAID actions on the mucosa, as well as with shifting of arachidonic acid metabolism from synthesizing protective prostaglandins to increased production of injurious leukotrienes. There is also evidence that patients with peptic ulcer disease have a deficiency of gastroduodenal mucosal prostaglandin synthesis, so that prostaglandins may play a pathophysiologic role in this disorder. Prostaglandins have a unique ability to prevent NSAID-induced gastric damage in humans, and also appear to improve ulcer healing during the continuation of NSAID therapy. PMID- 1940200 TI - Is there a role for dietary essential fatty acids in gastroduodenal mucosal protection? AB - A great deal is known about methods to diminish intragastric acid concentration, but far less is known about the ability of the gastroduodenal mucosa to resist injury or accelerate its healing. One group of compounds that plays a key role in the endogenous ability of the mucosa to protect itself against injury and perhaps to accelerate healing is the prostaglandins (PGs). The gastroduodenal mucosa synthesizes PGs from fatty acids precursors--predominantly linoleic and arachidonic. PGE1 or PGE2 have been shown to possess cytoprotective activity in the stomach and duodenum. In laboratory animals, linoleic acid feeding increased PG synthesis and diminished injury. When presented in a detergent solubilized form, arachidonic acid can also provide acute protection against injury by alcohol, bile acids, and aspirin. Arachidonic acid can also promote angiogenic response and thereby, perhaps, accelerate the healing process. Epidemiological evidence points toward a parallel between the decrease in peptic ulcer disease virulence and incidence and the total ingestion of linoleic acid by the population in the U.S. and the United Kingdom. Therefore, dietary essential fatty acids may play a key role in mucosal defense and restitution, and perhaps in the diminished incidence and virulence of peptic ulcer disease in the Western world. PMID- 1940201 TI - Gastrin: friend or foe of peptic ulcer? AB - Gastrin represents a direct pathogenic factor only in rare subgroups of ulcer patients, such as in the Zollinger-Ellison syndrome, the antral G-cell hyperplasia syndrome, and in patients in whom the gastric antrum was erroneously retained following partial gastrectomy. Gastrin may play a contributory role in the pathogenesis of uncomplicated peptic ulcer disease, as an exaggerated, but reversible gastrin release appears to be associated with Helicobacter pylori colonization. The known trophic effects of gastrin could account for the overall increase in the parietal cell mass of patients suffering from duodenal ulcer disease. Circumstantial evidence suggests that the abnormal gastrin release could also explain the upregulation of the parietal cell to the acid stimulatory effect and the consequent increase in gastrin sensitivity in patients suffering from duodenal ulcer disease. Conversely, the trophic effects of gastrin have also been linked to ulcer healing, especially since potent acid inhibitors induce a substantial hypergastrinemia. The evidence for such an association, however, is only circumstantial and potent and selective gastrin receptor antagonists are necessary to fully clarify the role gastrin exerts in ulcer healing. PMID- 1940203 TI - Epidermal growth factor in protection, repair, and healing of gastroduodenal mucosa. AB - Gastrointestinal mucosa is one of the most rapidly proliferating tissues in the body and the alteration in the balance between cell regeneration and cell loss may lead to mucosal lesions and ulcerations. Mucosal growth is under the influence of various growth factors, among which epidermal growth factor (EGF) and polyamines seem to play a crucial role. EGF is produced in large quantities in salivary and pancreatic glands and secreted mainly into the gut lumen and partly released into the bloodstream from where it is cleared by the kidneys and excreted into the urine as urogastrone. The physiological role of EGF is still under active investigations but it appears that EGF may be required for the maintenance of mucosal integrity and healing of mucosal defects due to its accumulation in the lesion area and local stimulation of healing processes. The mechanism of protective and ulcer healing effects of EGF involves the activation of ornithine decarboxylase (ODC), the key enzyme in the biosynthesis of polyamines, which play a crucial role in the growth-promoting action of EGF. Substances that affect the generation and/or catabolism of polyamines affect the gastroprotective and ulcer healing effect of EGF but not that of exogenous polyamines. Mucosal generation of protective prostaglandins appears to be essential mainly for the gastro-protective effects of EGF but seem to be of little importance in the healing effects of EGF on acute and chronic gastroduodenal ulcerations. PMID- 1940202 TI - Secretin as a potential mediator of antiulcer actions of mucosal protective agents. AB - Recently, we have reported that several nonacid agents including phenylpentol, methanol extract of licorice root (FM 100), plaunotol, and teprenon stimulate release of endogenous secretin in humans, dogs, and rats. The latter three are antiulcer agents developed in Japan that have a protective effect on the gastric mucosa. We have clearly shown that plaunotol inhibits postprandial gastrin release and gastric acid secretion that parallel the increase in plasma secretin concentration. It has also been recently demonstrated that the secretin-induced inhibition of gastric acid secretion in rats is completely blocked by indomethacin, a potent inhibitor of prostaglandin synthesis. It appears that the inhibitory action of secretin on gastric acid secretion is mediated mainly by endogenous prostaglandins. Because the three antiulcer agents FM 100, plaunotol, and teprenon have been shown to increase the content of endogenous prostaglandins in the gastric mucosa, endogenous secretin released by these agents may play a significant role in their mucosal protective action. It is concluded that the antiulcer effect of these drugs could in part be attributable to their unique ability to release endogenous secretin, and that secretin is a potential mediator of the antiulcer actions of mucosal protective agents. PMID- 1940204 TI - Gastric microcirculation and its regulating factors in stress. AB - Gastric mucosal blood flow and its regulating factors were studied in normal and stressed rats. In addition, vascular regulating factors and the role of CoQ10 anion radical and SOD (superoxide dismutase) level in gastric mucosa were also investigated as well as the influence of 5-HT (5-hydroxytryptamine) on gastric mucosal blood flow. Gastric mucosal blood flow was measured by the hydrogen gas clearance method. The vascular pattern of the stomach was investigated by the infusion method with two-colored silicon rubber. CoQ10 anion radical and SOD levels in gastric tissue were assayed by electron spin resonance (ESR) and radioimmunoassay. The gastric mucosal blood flow decreased significantly early after the induction of stress. Impairment of gastric mucosal blood flow was highly correlated with 5-HT and CoQ10 anion radical and SOD levels. Reduction in gastric mucosal blood flow was consequently due to opening of arteriovenular shunt and hyperpermeability of true capillaries influenced by 5-HT. These results demonstrate that ischemia and reperfusion after reduction of the gastric mucosal blood flow resulted in the sequence of events that led to formation of acute gastric mucosal lesions. PMID- 1940205 TI - Role of polyamines and prostaglandins in gastroprotective action of epidermal growth factor against ethanol injury. AB - Epidermal growth factor (EGF) exhibits its gastroprotective action against a variety of irritants and ulcerogens and plays an important role in healing of acute and chronic gastroduodenal ulcerations, but the mechanisms of these effects are not known. The present study was undertaken to determine whether polyamines (such as spermine or putrescine) and prostaglandins (PGs), which also show protective properties, contribute to the gastroprotective effect of EGF against ethanol injury in rats. It was found that both EGF and polyamines significantly and dose-dependently prevented the formation of gastric lesions induced by absolute ethanol, the effect being similar to that obtained with 16,16 dimethylprostaglandin E2. Pretreatment with indomethacin failed to affect the gastroprotective action of EGF and polyamines, suggesting that endogenous PGs may not play any major role in this protection. Our finding that the protective effect of EGF can be abolished by pretreatment with DFMO, an inhibitor of the polyamine biosynthetic pathway, suggests that gastroprotection by EGF is due, at least in part, to stimulation of biosynthesis of protective polyamines. PMID- 1940206 TI - Childhood parental loss and adult depression. AB - Previous research demonstrates convincingly that childhood parental deaths and parental divorces have implications for adult well-being as defined by levels of depression, educational attainment, early age at marriage, and risk of divorce. What this research has failed to examine are the interconnections among these outcomes. Specifically, are the socioeconomic and marital outcomes of parental loss implicated in the observed higher levels of depression? This analysis takes a first step in answering this question. Using data from a sample of 1,755 married men and women, I estimated regression models which examine the extent to which adult socioeconomic status and current marital quality mediate and/or modify the loss-depression relationship. Parental divorce was strongly related to socioeconomic and marital outcomes. Furthermore, current marital quality contributed importantly to understanding the higher levels of depressed mood observed among persons from divorced homes. Parental death was much more weakly related to socioeconomic and marital outcomes, and these outcomes played little role in explaining its relationship to depression. Finally, all of these relationships were stronger among women than men. These findings support the utility of life-course approaches to understanding adult mental health. PMID- 1940207 TI - Becoming married, depression, and alcohol problems among young adults. AB - This paper examines three questions regarding the relationship between marriage and mental health, specifically depression and alcohol problems. First, does marriage lead to improved mental health compared to never marrying? Second, do any mental health benefits of marriage primarily accrue to men? Third, what qualitative aspects of marriage are related to psychological disorder? We explore these questions in a longitudinal sample of young adults sampled at age 21 and again at age 24. We find no indication that marriage reduces depression. Married people do report fewer alcohol problems than the never-married but this could be due to the selection of less problematic drinkers into marriage. We also fail to find that men receive disproportionate mental health benefits from marriage. Finally, we find that marital conflict is associated with problem drinking for men and depression for women. The results indicate the importance of considering stage in the life cycle and gender-sensitive indicators of psychological disorder in studies of marriage and mental health. PMID- 1940208 TI - Stress from infertility, marriage factors, and subjective well-being of wives and husbands. AB - Stress associated with the inability to have a child is linked to four aspects of marriage and to five dimensions of life quality. Data come from 157 couples who met a standard medical definition for infertility. Wives and husbands were interviewed independently, and most of the following findings apply to both. A causal model suggests that fertility problem stress has direct effects that increase marital conflict and decrease sexual self-esteem, satisfaction with own sexual performance, and frequency of sexual intercourse. Also, fertility problem stress has both direct and indirect effects (via the marriage factors) that decrease evaluations of life-as-a-whole, self-efficacy, marriage, intimacy, and health. The negative effects on life quality are stronger for wives than for husbands. The model suggests that the life quality of couples with fertility problems could be improved if health care providers and couples themselves took steps to reduce such stresses and/or reduce their impact on the marriage factors. PMID- 1940209 TI - Convenience and independence: do physicians strike a balance in admitting decisions? AB - This paper contrasts economic and professional models of physician admitting behavior. Economic models emphasize physician convenience and income maximization, while professional models emphasize physician autonomy and independence. The paper examines the relative power of these models to explain two types of admitting decisions made by physicians: which hospitals to begin admitting patients to, and how many patients to admit to a hospital. Analyses of physician admitting patterns over a three-year period suggest that economic considerations outweigh professional considerations in both decisions. Results are interpreted in light of recent changes in the profession of medicine and physician-hospital relationships. PMID- 1940210 TI - A minor office: the variable and socially constructed character of death certification in a Scottish city. AB - Those doctors in a Scottish city who had completed the most death certificates in 1985 were identified, interviewed about their certifying practices, and asked, for comparative purposes, to complete a series of dummy death certificates, based on case summaries. Analysis of the dummy certificates indicated substantial inter practitioner variations in practice. From the interview data it is clear that the completion of death certificates is a very minor office: for most certifying doctors, death certification is an unsupervised, unreported, invisible, and unconsidered activity. It is argued that doctors who write large numbers of certificates conduct their certifications in Schutz's "world of routine activities" (Schutz 1970). It is this routinized orientation to certification that allows the practitioner to dwell within the "habitus" (Bourdieu 1977) of the medical collectivity but outside a normative order. Death certification may stand as an exemplar of a large number of medical activities, where wide and largely unacknowledged variations in practice occur with each practitioner investing his or her own practices with moral worth. Routinization ensures a moral order in the habitus, but not a normative order. PMID- 1940211 TI - Adolescent drug use, psychological distress, and physical symptoms. AB - The longitudinal interrelationships among general drug use, psychological distress, and physical symptoms were investigated in a three wave panel study of a community sample of adolescents interviewed when they were 12, 15, and 18 years of age. Results did not provide any support for the hypothesis that adolescents use drugs in general to cope with pre-existing psychological distress and physical symptoms. In contrast, the results supported the hypothesis that general drug use contributes to physical and psychological impairments over time. However, such drug-induced psychological distress and physical symptoms only occurred in later adolescence (from ages 15 to 18), and no evidence of impairments due to general drug use or specific alcohol use was found in early adolescence (from ages 12 to 15). Psychological distress and physical symptoms influenced each other over time, and physical symptoms partially mediated longitudinal changes in psychological distress. However, general drug use did not mediate any longitudinal changes in psychological distress and physical symptoms. PMID- 1940212 TI - The effectiveness of stigma coping orientations: can negative consequences of mental illness labeling be avoided? AB - Recent research has assigned a prominent role to labeling and stigma as factors that impair the social and psychological functioning of people officially labeled mentally ill. But can the effects of labeling and stigma be overcome by adopting a few simple approaches to coping with these problems? If so, the stigma-induced problems of social awkwardness, demoralization and unemployment emphasized by recent research may not be as severe as claimed. Using a sample of psychiatric patients, we examine this issue by assessing whether patients can ameliorate labeling effects by keeping their history of treatment a secret, educating others about their situation, or avoiding situations in which rejection might occur. None of these coping orientations were effective in diminishing negative labeling effects on unemployment or on psychological distress/demoralization. In fact, the three coping strategies show consistent effects in the direction of producing more harm than good, and with respect to withdrawal-avoidance this effect is significant. Based on these results we argue that stigma is powerfully reinforced by culture and that its effects are not easily overcome by the coping actions of individuals. Using C. Wright Mills's (1967) distinction we conclude that labeling and stigma are "social problems" not "individual troubles." PMID- 1940213 TI - An in vivo chloroquine sensitivity study in relation to low transmission potential and imported malaria in Kerala. AB - The study highlights the presence of chloroquine resistant Plasmodium falciparum strains in Kerala state, India for the first time. The emergence of chloroquine resistant P. falciparum in a low transmission area is dependent on the imported cases while build up of resistance is mainly due to persistence of resistant parasites which have more opportunities for transmission. PMID- 1940214 TI - Changing response of Plasmodium falciparum to chloroquine in West Bengal during 1980-1988. AB - A total of 314 cases of Plasmodium falciparum malaria studied during 1980-88 in nine times monitoring revealed three RIII foci i.e. two in Jalpaiguri and one in Purulia districts. The studies showed a parasite clearance of 40 per cent and 32 per cent of P. falciparum cases within seventh day in Purulia and Jalpaiguri districts respectively, with a dosage of 25 mg per kg body weight, spread over three days in divided doses. Increase in transmission potential and prolonged drug pressure with single drug have been noted in association with development of resistance. Malaria parasite clearance time (MPCT) value of sensitive and resistant cases reach parallelism and malaria parasite recrudescence time (MPRT) value starts declining, giving an indication of stabilisation of genetic change in the parasite. PMID- 1940215 TI - A quantitative survey of anophelines in six villages of Kheda District, Gujarat. AB - Sampling of anophelines from six villages of Kheda district, Gujarat was done using four different methods viz. indoor resting, outdoor resting, bovine bait trap and immature collections. A total of 113,487 specimens representing 17 species were collected. An. subpictus (66.51 per cent) was most abundant species followed by An. culicifacies (14.12 per cent) and An. tessellatus (5.24 per cent). Bovine bait collections were found most productive yielding maximum species and highest number of anophelines per unit of collection efforts. Indoor resting collections yielded poorest diversity and greater number of specimens per unit of collection effort than outdoor resting collections. Maximum diversity was observed in outdoor collections. Most of the species exhibited unimodal prevalence. PMID- 1940216 TI - Man vector contact in microfilaraemic and amicrofilaraemic human population--a case control study. AB - A case control study was undertaken in rural areas of Varanasi, U.P., to study the relationship of Culex quinquefasciatus landing on microfilaria--carriers and amicrofilaraemic controls. No statistically significant difference was observed in the vector landing in these two groups. PMID- 1940217 TI - Long term effect of diethylcarbamazine medicated common salt on bancroftian filariasis. PMID- 1940218 TI - Serodiagnosis of Indian kala-azar: evaluation of IFA, ELISA and CIEP tests. AB - The sensitivity and specificity of three serological tests viz. indirect immunofluorescent antibody test (IFAT), enzyme linked immunosorbent assay (ELISA) and counterimmunoelectrophoresis (CIEP) for the diagnosis of Indian kala-azar were evaluated. Of the 209 patients in whom Leishmania donovani parasite could be demonstrated in bone marrow, 207 (99.04 per cent) could be diagnosed with IFAT, 203 (96.6 per cent) with CIEP and 208 (99.5 per cent) with ELISA. None of these serological tests was positive in 40 healthy individuals and 10 patients each with tuberculosis, toxoplasmosis and malaria. In only one out of 10 patients with malaria ELISA alone gave false positive result. Of the 119 patients who had clinical features simulating kala-azar but were negative for Leishmania donovani in bone marrow and responded to treatment other than that for Indian Kala-azar, IFAT, CIEP and ELISA were false positive in three (2.5 per cent), nil and three (2.5 per cent) cases, respectively. The use of serodiagnostic tests like ELISA for mass screening and CIEP in less well equipped peripheral laboratories is suggested. PMID- 1940219 TI - Leishmanin skin test in clinical and subclinical kala-azar cases. AB - Leishmanin skin test was done on 25 active kala-azar (KA) patients, 41 healthy persons residing with KA patients and 14 treated cases of KA. All active cases of KA were Leishmanin test negative. Nine out of 41 (21.9 per cent) healthy household members gave positive reaction to Leishmanin antigen. These persons were previously exposed to Leishmania donovani infection which was overcome by developing cell mediated immunity. The infection in these persons remained subclinical or asymptomatic. This shows that all L. donovani infections do not progress to clinical stage. PMID- 1940220 TI - Demographic features of sporadic acute hepatitis as determined by viral hepatitis markers. AB - The demographic features of acute x sporadic viral hepatitis as diagnosed by specific markers of viral infection in four different cities in north and north east India, were examined. Of 405 patients examined, 26 per cent had HB,Ag, 5.9 per cent IgM-anti-HAV antibody, and 8.4 per cent IgM-anti-HBc antibody. Hepatitis B occurred more frequently in male patients (76 per cent) compared to hepatitis A (54 per cent), and in the young adult age group (21-30 years), compared to the latter, which occurred predominantly in children (0-10 years). By using tests to detect HbsAg and IgM-anti-HBc antibody, this study found that hepatitis B accounted for 3 per cent and 8.8 per cent of clinically detected acute sporadic hepatitis in patients less than and older than 10 years of age respectively, which is in contrast with previously-reported rates from India. This study also suggests that many of the infections thought to have been due to HBV, may be due to NANB hepatitis virus. This study emphasizes the importance of specific laboratory tests to draw epidemiologic conclusions regarding hepatitis. PMID- 1940221 TI - Comparison between indirect fluorescent antibody and Weil-Felix tests for detecting antibodies against rickettsia. AB - Comparative evaluation of indirect fluorescent antibody test (IFAT) and Weil Felix test (WFT) was carried out for detecting rickettsial antibodies in 102 patients with pyrexia of unknown origin (P.U.O.), 20 brucellosis cases and 20 normal healthy controls (N.H.C.). Of 102 sera of cases with P.U.O., antibodies against rickettsia could be detected in 11 (10.7 per cent) cases by IFAT and in 10 (9.8 per cent) cases by WFT, but amongst these 10 sera, antibodies could be detected only in six by IFAT. All 20 brucella positive sera were negative for rickettsia by IFAT but by WFT in 6 sera antibodies against rickettsia could be detected and 20 N.H.C. sera were negative by both the tests. Thus the advantages of IFAT over WFT in detecting antibodies against rickettsia in terms of sensitivity and specificity make it a more reliable test. PMID- 1940222 TI - Evaluation of different commercial kits for HIV/HTLV-III EIA. AB - Choice of an ideal, cost-effective and rapid diagnostic test for HIV infection is of immense value in developing countries like India where resources are limited. A number of commercial HIV antibody testing kits are now available with varying sensitivities and specificities. Six different commercial HIV kits namely, Wellcozyme, Flow HIV-TEKG, Abbott HIV EIA, Abbott VIA, Dip-stick EIA and Abbott env/core recombinant EIA were evaluated. Du-Pont Western blot (W.B.) kit was used as gold standard to compare the results. Of the 376 sera from various high-risk individuals screened, Wellcozyme kit yielded 100 per cent concordant results with W.B. Abbott VIA and Abbott env/core also yielded results in confirmation with W.B., excepting the fact that both detected one extra sample positive, which was negative in W.B. Abbott EIA yielded 4 false positive results. Dip-stick kit yielded the maximum number of false positives. The study indicated that 3 kits, namely Wellcozyme, Abbott VIA and Abbott EIA could be used to achieve optimum and acceptable results. PMID- 1940223 TI - Comparison of enzyme linked immunosorbent assay and indirect haemagglutination test in serologic diagnosis of toxoplasmosis. AB - The antibody response against Toxoplasma gondii was evaluated by ELISA and indirect haemagglutination test (IHA) in 100 antenatal cases with bad obstetric history. 30 per cent of the cases were found to be positive by the IgM ELISA test and 22 per cent were positive by the IHA test. ELISA was found to be a more specific, reliable and easy test for screening of antenatal cases. PMID- 1940224 TI - Nocardia associated with pulmonary tuberculosis. AB - A total of 209 cases of pulmonary tuberculosis were screened for the presence of Nocardia in their sputa. In 2.9 per cent of the cases Nocardia asteroides was isolated. The increasing importance of this microorganism has been discussed in the light of other reports from India. PMID- 1940225 TI - Plant sources of fructose to sandflies, particularly Phlebotomus argentipes in nature. PMID- 1940226 TI - Mosquito collections by light traps in Bastar. PMID- 1940227 TI - A preliminary observation on larval diapause of Phlebotomus argentipes (Diptera: Psychodidae). PMID- 1940228 TI - Outbreak of soya milk poisoning in Delhi. PMID- 1940229 TI - Vector control through environmental management with special reference to India- approach prospectives. AB - The introduction of different types of pollutants like those from industrial effluence, bye-products from petro-chemical industries, pesticidal application, wastages of nuclear power industries, etc. is viewed seriously by the society. For the control of vectors of disease the adoption of environmental management is, therefore, imperative. The physical methods like drainage of excess and waste water, making water unsuitable for vector breeding by adopting various indigenous methods in vogue, the intra and inter-sectrol coordination and community based activities are identified as the basic approaches for achieving this goal. Minimising the potentiality of vector breeding through source reduction and water management is thought to be the simplest, cheapest and most permanent method. For the society having varying types of habitation and varying degree of habitational facilities like planned housing, water supply and disposal, sanitation and organized anti-vector measures, the adoption of environmental management to exercise check over vector population is a promising proposition. The suitability of such an approach has already been demonstrated by MRC, (ICMR), Delhi and V.C.R.C., Pondicherry. The implementation of these methods is to be initiated right from Primary Health Centre and district level onwards and community is to be motivated to the extent that the various methods of environmental management for vector control are adopted in the routine way of life. In the present article these ideas have been touched upon and various methods of environmental management described in brief. In addition what other Governmental agencies are required to do in order to effectively implement environmental management methods are briefly enlisted. PMID- 1940230 TI - Malaria as anthropo-ecosystem. Part VI: Demographic subsystem (DSS). AB - Demographic Subsystem (DSS) comprising structure, distribution, along with its dynamic process has been identified to influence Malaria as Anthropo-Ecosystem (MAES) broadly in two ways. Innate characters of some essential elements of DSS viz. growth, age and sex composition, infants, children, young and old adults, non-pregnant and pregnant and lactating mothers exert direct influence while other elements, viz. spatial distribution, density, configuration of settlements and migration are influenced by environmental factors and affect MAES indirectly. Attempt has been made to discuss each of these factors in the light of present knowledge and available data. PMID- 1940231 TI - Rate of clearance of ethanol from the blood of intoxicated patients in the emergency department. AB - One hundred and three patients presenting to the Mt. Sinai Medical Center emergency department (ED), who appeared on clinical grounds to be acutely intoxicated, were studied to determine the rate of clearance of ethanol from blood. The mean presenting serum ethanol level was 299 mg/dL. The rate of clearance was found to be 20.43 mg/dL/h with a standard deviation of 6.86 mg/dL/h. No correlation was found between rate of ethanol clearance and serum levels of amylase, alkaline phosphatase, glutamate-oxaloacetate or glutamate pyruvate transaminase, lactic dehydrogenase, or total bilirubin. Similarly, no correlation was found between rate of clearance and race, sex, age, or time of day. We conclude that although the average patient presenting to the emergency department will clear ethanol at about 20 mg/dL/h, a standard deviation of 6 mg/dL/h means that only 83% of these patients will have clearance rates between 8 and 32 mg/dL/h, and that if accurate estimates are necessary, serial determinations of two or more levels are needed. PMID- 1940233 TI - Prevention of oral bacterial flora transmission by using mouth-to-mask ventilation during CPR. AB - The Emergency Cardiac Care Committee of the American Heart Association has recently recommended utilizing protective barrier precautions during CPR (1,2). We assessed 17 mask and faceshield resuscitation devices for adequacy of barrier protection. Eight of the devices were faceshields (CPR Microshield, Hygenic, MedCare Mask, Resusci, Samaritan, Sealeasy, Portex); 8 were mask devices (Laerdal, Dyna Med, MTM Emergency Lung Ventilator, MTM Emergency Resuscitator, Res-Q-Flo, Rightway Mouth-to-Mask Resuscitation, Trufit), and one of the devices did not meet the criteria for either faceshield or mask (Lifesaver). All masks were disinfected, applied to the investigator's face as directed by the manufacturers' instructions, and then cultured for oral aerobic bacterial flora on the rescuer side. No mask devices cultured positive for oral aerobic bacterial flora, while 6 of 8 faceshield devices cultured positive for oral aerobic bacterial flora (P less than 0.007). The CPR Microshield and the Portex faceshield were the only devices that did not develop a positive culture. We conclude that all ventilation devices with a one-way valve, except the Sealeasy device, provide adequate barrier type protection from oral aerobic bacterial flora when simulating mouth-to-barrier type protection when performing mouth-to mouth ventilation. PMID- 1940232 TI - Sympathetic responses in out-of-hospital cardiac arrest. AB - To determine the clinical relevance of the sympathetic response to out-of hospital cardiac arrest, we measured plasma concentrations of catecholamine and cortisol in ten such arrested patients on their arrival. The duration of cardiac arrest was estimated from 9 to 200 min before basic life support was initiated by ambulance personnel. Two of the patients developed spontaneous pulses in response to ALS and were resuscitated, and the others were not, although the length and the extent of ALS were not different between the two groups. Plasma concentrations of epinephrine (EN), norepinephrine (NE) and cortisol prior to ALS in both groups were markedly elevated. In particular, the patients who never regained spontaneous pulses showed 58-fold and 12-fold increase in the plasma EN and NE levels, respectively, which were much higher than those in the resuscitated cases; 8- and 1.7-fold increase, respectively. These massive EN and NE discharges correlated well with the arrest time (r = 0.96 and 0.94, respectively) and the degree of acidosis (r = -0.82 and -0.82, respectively). PMID- 1940234 TI - The reversal of the ischemic effects of epinephrine on a finger with local injections of phentolamine. AB - The use of phentolamine (Regitine) as a specific competitive antagonist of epinephrine by virtue of its alpha-blocking properties is well known. Its use via digital nerve block infiltration has been described in cases of IV infiltration of sympathomimetics. We discuss a recent case of local and direct infiltration of phentolamine along the course of the digital arteries and directly into the thumb tuft to reverse the local ischemic effects of epinephrine. PMID- 1940235 TI - Pneumomediastinum as a complication of upper gastrointestinal endoscopy. AB - Secondary or complex pneumomediastinum following esophagoscopy is due to an esophageal perforation. Primary or simple pneumomediastinum may be caused by maneuvers such as coughing, gagging, swallowing, choking, and valsalva. These maneuvers are common during upper gastrointestinal endoscopy. Esophageal perforation is a potentially life threatening event, while simple pneumomediastinum is usually a benign self-limited disorder. Although the presentation may be similar, different morbidities compel prompt evaluation for distinction between these two entities and appropriate management. We present a case of pneumomediastinum that developed immediately following upper gastrointestinal endoscopy. Implications of diagnosis, management, and prognosis are discussed. PMID- 1940236 TI - Rare congenital anomalies simulating upper cervical spine fractures. AB - Congenital anomalies of the cervical spine are rare, especially those involving the atlas. Two cases are reported, one each of an unfused anterior arch and an unfused posterior arch of C1 that on plain film radiographs simulated unusual odontoid fractures. A general discussion of the development of the dens and the atlas follows. PMID- 1940237 TI - Intussusception in the adult--a rare disease. AB - We present two cases of intussusception in the adult. Both cases were secondary to a benign lipoma as the lead point. These cases represent typical cases of adult intussusception, a rare disease characterized by insidious onset, vague abdominal symptoms, and elusive diagnosis. A diagnostic and therapeutic approach to adult intussusception is suggested. The need to consider this rare entity in the differential diagnosis of chronic abdominal complaints in the adult is emphasized. PMID- 1940239 TI - Unusual cases of intussusception. AB - Intussusception occurs most commonly in the first five years of life and is classically associated with intense intermittent abdominal pain, vomiting, bloody mucoid diarrhea, and a palpable abdominal mass. These cardinal findings are frequently not present, however, particularly outside the usual age range. The emergency physician must therefore be vigilant in considering intussusception as a potential cause for intestinal obstruction in all patients, if ischemic complications are to be avoided. We present three cases of "unusual" intussusception, and provide a review of this entity and a guide to its consideration and work-up in the emergency department. PMID- 1940240 TI - Diltiazem overdose: case report and review. AB - We present a case of diltiazem overdose in which the patient ingested 4.2 grams in an apparent suicide attempt. He arrived in the emergency department two hours postingestion with a blood pressure of 60/40 torr and a heart rate of 62 beats/min in a junctional rhythm. Intervention included activated charcoal, gastric lavage, intravenous fluids, calcium (both chloride and gluconate), dopamine, and atropine with improvement in vital signs. Diltiazem levels were obtained and half-life calculated. This ingestion is one of the largest reported in the literature and is remarkable in that the patient recovered without pacing or other extraordinary measures. All eight previously published cases of diltiazem overdose, including all unpublished reports to the manufacturer, are reviewed and their management strategies examined. Successful treatment in which recovery has occurred in less than 48 hours, includes pressors, calcium, glucagon, pacing, and charcoal hemoperfusion. A strategy for emergency physicians to use when approaching this problem is suggested from the review. PMID- 1940238 TI - Aortoenteric fistula in a 21-year-old. AB - We present the case of a 21-year-old male with recurrent, severe gastrointestinal hemorrhage, who eventually proved to have an aortoduodenal fistula. The fistula arose from an aortic repair done after a stab wound four years previously. The diagnosis of aortoenteric fistula was not initially suspected because of the patient's age, inability to provide details of his previous surgery, and false negative endoscopic and radiologic studies. We believe that this is the youngest reported patient who developed an aortoenteric fistula after aortic surgery. The presence of an aortoenteric fistula should be suspected in any patient with a GI bleed and previous aortic surgery, regardless of the patient's age. PMID- 1940241 TI - High pressure injection injuries: an overview. AB - Injuries resulting from the use of high pressure injectors and spray guns are relatively rare; however, the potential tissue damage caused by the injury as well as the extent of the injury itself may go unrecognized by the primary physician. The purpose of this paper is to inform the emergency physician of the nature and standard management of this type of injury. A basic understanding of the pathophysiology of the high pressure injection injury (HPII) is essential in avoiding the mistakes in management that have been reported in the literature. The emergency management of the HPII includes: evaluation and immobilization, tetanus and antimicrobial prophylaxis, supportive and resuscitative measures, analgesia, and minimizing the time to definitive surgical treatment. PMID- 1940242 TI - A private view. PMID- 1940243 TI - Use of famotidine for the treatment of urticaria. PMID- 1940244 TI - Descriptive analysis of residency-trained emergency medicine physicians. AB - The purpose of this study was to analyze the demographics, practice characteristics, and job satisfaction of physicians who completed emergency medicine residencies. A questionnaire was mailed to 858 physicians who graduated from residencies between 1978 and 1982. A 62.8% response rate (n = 539) was achieved. The majority of respondents were satisfied or very satisfied with their choice of a career in emergency medicine and with the quality of their residency training. Over 22% of respondents cited lack of preparation to perform administrative tasks as a significant weakness of their residency training. The results of survey indicate that emergency medicine physicians are engaged primarily in clinical practice, but that administrative duties increase rapidly in the years following residency graduation. Emergency medicine physicians are still highly concentrated in states in which emergency medicine residencies are located. The percentage of graduates choosing academic careers is smaller than reported in studies of earlier graduates. PMID- 1940245 TI - The daily cercarial emission rhythm of Schistosoma margrebowiei with particular reference to dark period stimuli. AB - The cercariae of Schistosoma margrebowiei showed two peaks of emergence from Bulinus natalensis in a 12 h light/dark cycle. Peak emission occurred at 0700 h (one hour after the onset of light) and at 1900 h (one hour after the onset of darkness). Both peaks were of equal magnitude and were maintained during constant illumination indicating that the rhythm is innate. Delaying or advancing the timing of the dark period did not affect the timing of these two peaks. Following a five minute dark treatment elevation in cercarial output resulted irrespective of when the treatment was applied. Subjecting snails to various intensities of light only resulted in an elevation in output when a sudden change in intensity from 0 to 360 Lux or the reverse was applied. No response was seen to a gradual change in light intensity although the parasite could detect a change in light from 1 to 0 Lux. These responses appear to optimize the chances of host parasite contact. PMID- 1940246 TI - Studies on the infectivity of Diplostomum spathaceum in rainbow trout (Oncorhynchus mykiss). AB - The infectivity of Diplostomum spathaceum (Digenea: Trematoda) cercariae to rainbow trout and the efficacy of the diplostomule migration to the lens following different routes of administration was examined. The optimum age of infectivity for cercariae was between 0-5 h after liberation from the snail and for intraperitoneally injected diplostomules, 5 h post-transformation in vitro through fish skin. After exposure of the entire fish body or head to cercariae, metacercariae first appeared in the lens at 5 h and their numbers gradually increased until 22 h. Following exposure of the tail region of rainbow trout to cercariae, metacercariae first appeared in the lens at 14 h. Significantly more metacercariae established in the lens of fish following exposure of the fish head compared with the tail region; 40% of penetrating cercariae reached the lens of fish following exposure of the head or entire body, 20% of cercariae or diplostomules injected either intraperitoneally, intramuscularly or intracardially reached the lens while only 5% of cercariae established as metacercariae following exposure of the tail region. PMID- 1940247 TI - Effect of water temperature on the ability of Diplostomum spathaceum miracidia to establish in lymnaeid snails. AB - The effects of water temperature on the ability of Diplostomum spathaceum miracida to infect and establish patent infections in Lymnaea peregra and L. stagnalis were investigated. Snails were infected over a range of temperatures (6 20 degrees C) and kept thereafter at 20 degrees C or were infected at 20 degrees C and kept at either 14, 20, or 25 degrees C. Infection success was determined after 8 weeks by either observing cercarial shedding or examining snail viscera for sporocysts. The establishment of miracidia declined at lower water temperatures despite maintenance for 8 weeks at 20 degrees C while exposure of snails to miracidia at 20 degrees C and maintenance at different temperatures had little apparent effect. Infection success under these conditions was related more to the numbers of miracidia to which the snails were exposed. However, under this latter experimental regime, the time taken for the infection to become patent clearly depended upon maintenance temperature. PMID- 1940248 TI - Some enzymes of carbohydrate metabolism in Mesocestoides corti and Heterakis spumosa. AB - The activities of selected enzymes of carbohydrate metabolism were measured in tetrathyridia of Mesocestoides corti and in adult females and males of Heterakis spumosa. When the species were compared, only lactate dehydrogenase and phosphoenolpyruvate carboxykinase activities were considerably higher in M. corti. Activities of other enzymes were higher in H. spumosa, with malate dehydrogenase activity being considerably so. In H. spumosa, enzyme activity was higher, and succinate dehydrogenase markedly so in males, when compared with females. Tetrathyridia aged 170 and 210 days show relatively stable malate and lactate dehydrogenase activities, and mice of ICR and BALB/c strains are suitable for the maintenance of tetrathyridia. PMID- 1940249 TI - In vitro stress selection of nematophagous fungi for biocontrol of parasitic nematodes in ruminants. AB - Laboratory experiments were designed to select nematophagous fungi that were able to survive in vitro conditions simulating passage through the gastro-intestinal tract of cattle. All of the tests were conducted at 39 degrees C. In a primary stress selection step in diluted rumen fluid, 21 isolates were obtained. Each of the primary stress selected isolates was tested in synthetic saliva, rumen fluid simulating the activity in the rumen, rumen fluid followed by pepsin-hydrochloric acid treatment simulating the additional effect of ruminal and abomasal activity, pepsin-hydrochloric acid solution simulating conditions in the abomasum and finally in a trypsin solution as an example of enzyme activity in the gut. The effect of the rumen fluid alone, or rumen fluid followed by pepsin-hydrochloric acid treatment, were responsible for the reduction in surviving fungal isolates. Only six of thirteen isolates belonging to the genus Arthrobotrys survived while seven of eight isolates of the genus Duddingtonia survived. Fourteen isolates were tested for their predatory capacity in a dung pat bioassay. Fungi of the genera Arthrobotrys and Duddingtonia reduced the development of Ostertagia ostertagi third stage larvae by approximately 75% and 96% respectively compared to the number of larvae that developed from fungus-free control pats. PMID- 1940250 TI - Survival of sheep and goat first stage protostrongylid larvae in experimental conditions: influence of humidity and temperature. AB - The survival of first-stage larvae of a laboratory strain of Muellerius capillaris and of a natural multispecific infection (Neostrongylus linearis, Cystocaulus nigrescens, Protostrongylus rufescens) was studied for 10 to 12 day periods. The survival was estimated either on larvae in faeces or kept in tap water. Temperature (-18 degrees C to 37 degrees C) and desiccation were the ecological factors investigated. M. capillaris was the most tolerant to these factors but showed better survival at 4 degrees C (and at -18 degrees C on one occasion). N. linearis survived better at 25 degrees C or -18 degrees C and C. nigrescens at 4 degrees C and -18 degrees C. Humidification of faeces was unfavourable to the latter species. All the species could stand desiccation of faeces up to 67% of dry-matter for M. capillaris or 82% for other species. Larval survival estimated for L1 in tap water was different from that estimated for larvae in faeces. The variation in resistance to unfavourable temperatures or moisture conditions may account partly for the geographical distribution of the species. PMID- 1940251 TI - Chromosome numbers in Onchocerca dukei and O. tarsicola. AB - Testicular examination of male Onchocerca dukei and German O. tarsicola revealed five pairs of chromosomes, which is typical of most filariae. In contrast to German O. tarsicola, specimens from Sweden had only three pairs of chromosomes. PMID- 1940253 TI - Recovery of adult stages and microfilaraemia after low dose inoculation of third stage larvae of Litomosoides carinii in Sigmodon hispidus. AB - Because of the negative binomial distribution of filarial third stage larvae (L3) in their vectors, under natural conditions only a few are usually transferred per bite. After an inoculation of 5 L3 per animal into eight host animals at least one developed a long lasting patency based on one reproductive female only. After an inoculation of 15 L3, three of eight animals developed long lasting patency, harbouring between two and five fertile females. The rates of adult stages recovered were 0.43 and 0.30 respectively. The parasitaemias of the six patent animals in both experimental groups increased with the number of reproductive females present (r = 0.89, p = less than 0.005). All non-patent animals which were mf-negative in the pleural fluid and lung blood as well had a single sex or no worm load. In only one animal was there an apparently normal but non reproductive pair of worms without any pathological alterations of the host animal. Encapsulated adult worms were found rarely, but independent of the final worm load or inoculation dose and always beside normal adults. In three of the 16 animals inoculated with 5 or 15 L3 patency passed after 10-12 weeks p.i., in two others it seemed to pass soon. After inoculation of 30, 40 or 60 L3 per animal patency passed early in about one half of 105 animals, when they were observed up to 24-36 weeks p.i. In conclusion all types of host defensive reactions are already visible after inoculation with such small doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940252 TI - Acanthocheilonema viteae (Dipetalonema viteae) in mice: differences in the relative binding of microfilarial surface-specific antibody may explain the contrasting response phenotypes of BALB/c and C57BL/10. AB - Experiments were carried out to obtain additional data concerning the role of IgM antibodies, specific for the cuticular surface of the microfilariae (mf) of A. viteae, in clearing microfilaraemia from high- and low-responder mice infected by transplanted adult worms. Although BALB/c mice, which sustain a chronic microfilaraemia, produced IgM mf surface-specific antibodies, the binding to target mf was weak when compared to that of antibodies from the serum of the resistant C57BL/10 mice. Furthermore, antibodies from BALB/c mice were not as efficient as those from C57BL/10 mice in promoting the adherence of immune or control leukocytes to mf in vitro. Evidence is provided to show that mf shed surface bound antibody. Although the results do not establish conclusively the mechanism underlying the contrasting response phenotypes of C57BL/10 and BALB/c mice, they provide support for the involvement of antibody in controlling microfilaraemia and suggest that quantitative and qualitative differences in the amount and affinity of IgM antibody specific for the mf surface, together with the natural tendency of the mf to shed surface bound antibody at 37 degrees C, may combine to allow the former strain to clear microfilaraemia efficiently whilst the latter sustains a chronic infection. PMID- 1940254 TI - First record of the larval parasitic nematode Rhabditis orbitalis from Japanese wood mice (Apodemus spp.). AB - Parasitic larvae of Rhabditis orbitalis (formerly confused with Pelodera strongyloides) were found in the conjunctival sacs of the eyes of Apodemus argenteus and A. speciosus from Japanese islands. PMID- 1940255 TI - Cocaine and the liver. PMID- 1940256 TI - Prevention of recurrent variceal bleeding in alcoholic cirrhotic patients: prospective controlled trial of propranolol and sclerotherapy. AB - We conducted a prospective randomized controlled study to evaluate the effectiveness of propranolol and sclerotherapy, compared to a control group, in the prevention of variceal rebleeding in alcoholic cirrhotic patients. Among the 79 patients included, the distribution of patients according to Child-Pugh classification was: A, 22%; B, 40%; and C, 38%. Propranolol was given twice daily with a mean final dose of 54 +/- 16 mg/day, this resulted in a mean reduction in resting heart rate of 26 +/- 7%. Sclerotherapy was performed weekly using 1% polidocanol. End points were rebleeding or death. During the mean follow up of 19 +/- 16 months, 43 patients bled and 22 patients died. The cumulative percentages of patients free of rebleeding at 1 year were: propranolol, 81% (95% confidence interval (CI): 63-92); sclerotherapy, 64% (95% CI: 45-82); control, 54% (95% CI: 36-71); these differences did not reach statistical significance. The cumulative percentages of patients alive at 1 year were: propranolol, 92% (95% CI: 76-98); sclerotherapy, 79% (95% CI: 58-91); control, 81% (95% CI: 60-93); these differences were not statistically significant. Alcohol withdrawal, which occurred in 66% of patients, was an independent predictive factor associated with a decreased risk of rebleeding or death. In conclusion, a life table analysis of patients free of rebleeding, as well as of patients surviving, revealed a tendency in favour of propranolol. The lack of a statistical support for these two favorable effects could be due to poor statistical power.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940257 TI - Effect of Silibinin on biliary lipid composition. Experimental and clinical study. AB - The effect of Silymarin, a natural flavonoid, on biliary lipid composition, was studied in rats and humans. Bile flow, biliary cholesterol, phospholipid and total bile salt concentrations were measured in 23 control rats and in 27 rats treated with Silibinin, the active component of Silymarin, at the dose of 100 mg/kg body weight i.p. (n = 21) or 50 mg/kg body weight i.p. (n = 6) for 7 days. Biliary cholesterol and phospholipid concentrations were significantly reduced after the higher Silibinin dose (60.9 and 72.9% of the control values), whereas bile flow and biliary total bile salt concentration were unchanged. After the lower Silibinin dose all parameters remained unchanged. Total liver cholesterol content was not affected by Silibinin. On the other hand, in vitro determination of rat liver microsomal 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity showed a significant dose-dependent inhibition by Silibinin (0.5-8 mg/kg). Biliary lipid composition was also assayed in four gallstone and in 15 cholecystectomized patients before and after Silymarin (420 mg per day for 30 days) or placebo administration. In both groups, biliary cholesterol concentrations were reduced after Silymarin treatment and the bile saturation index significantly decreased accordingly. These data suggest that Silibinin induced reduction of biliary cholesterol concentration both in humans and in rats might be, at least in part, due to a decreased synthesis of liver cholesterol. PMID- 1940258 TI - Inhibitors of the lipoxygenase arachidonic acid pathway impair glycocholate efflux in isolated rat hepatocytes. AB - Lipoxygenase arachidonic acid metabolites mediate secretory processes in several tissues, but their possible involvement in liver transport functions is still unknown. This study evaluated the influence of the lipoxygenase inhibitor nordihydroguayaretic acid (NDGA), the cyclooxygenase inhibitor indomethacin (INDO), and the dual cyclo and lipoxygenase inhibitors 3-amino-1-[m (trifluoromethyl)-phenyl]-2-pyrazoline (BW 755c) and eicosatetraynoic acid (ETYA) on the handling of glycocholic acid (GC) by isolated rat hepatocytes. No drug modified cell viability or oxygen consumption in hepatocytes. In 30-min incubations with 50 microM GC the initial rate of GC uptake (V0) in control hepatocytes was 1.15 +/- 0.09 nmol.mg protein-1.min-1. The cellular GC content remained constant from 10 to 30 min (steady-state phase), the 30-min value being 6.63 +/- 0.35 nmol.mg protein-1. NDGA (10-50 microM), BW 755c (25-200 microM) and ETYA (5-100 microM), prevented the steady-state phase occurring, thus determining a progressive accumulation of GC in cells with time. As compared to controls, 50 microM NDGA (+37%, p less than 0.01), 200 microM BW 755c (+39%, p less than 0.01) and 5 microM ETYA (+19%, p less than 0.05) induced the highest increases in the amount of GC in cells at 30 min, in all cases V0 being unchanged. Concentrations of BW 755c and ETYA above those indicated also decreased V0. Both V0 and the amount of cellular GC in the steady-state phase were proportionally decreased by high INDO concentrations (25-100 microM) which did not modify the morphology of the uptake curve. Since experiments with dual and lipoxygenase inhibitors suggested an impairment of GC efflux, the initial rate of GC efflux (V0ef) was measured in hepatocytes preloaded with 50 microM GC and transferred to a GC-free medium. In controls, V0ef was 1.12 +/- 0.12 nmol.mg protein-1.min-1. BW 755c (200 microM) and NDGA (50 microM) reduced V0ef by 45 and 38%, respectively. The kinetic analysis of the effect of 200 microM BW 755c on the efflux process using hepatocytes preloaded with GC from 5 to 200 microM disclosed a non-competitive inhibition. Vmax was reduced from 1.37 +/- 0.15 to 0.89 +/- 0.10 (p less than 0.01), whereas Km was unchanged (3.79 +/- 0.33 vs. 4.25 +/- 0.54, N.S.). In summary, inhibitors of the lipoxygenase arachidonic acid pathway impaired the efflux of GC from isolated rat hepatocytes. The hypothesis is raised that oxidized metabolites of arachidonic acid may participate on the secretion of bile salts in these cells. PMID- 1940259 TI - Hepatic dysfunction accompanying acute cocaine intoxication. AB - We identified 39 patients with acute cocaine intoxication and rhabdomyolysis over an 8-year period. Twenty-three of the patients (59%) demonstrated biochemical evidence for hepatic dysfunction. Sixteen of these patients had severe liver injury as defined by an alanine aminotransferase (ALT) of greater than 400 U/l (group A). Seven had an ALT between 36-399 U/l (group B) and 16 showed no evidence of liver injury (group C). In contrast to those with normal ALT, the clinical course of the group A patients was more often accompanied by profound hypotension (44 vs. 0%, p less than 0.025), disseminated intravascular coagulation (50 vs. 0%, p less than 0.005), hyperpyrexia (75 vs. 25%, p less than 0.025) and acute renal failure (81 vs. 0%, p less than 0.001). Seven of the group A patients expired (44%). Histologic examination of liver tissue obtained from post-mortem samples demonstrated extensive centrilobular and midzonal necrosis in three cases and panlobular necrosis in two others. A mild lymphocytic infiltrate with bile duct proliferation was present in each specimen. We conclude that cocaine intoxication can be accompanied by liver dysfunction which is most likely multifactorial; the presence of severe dysfunction identifies a patient with potentially significant morbidity and mortality. PMID- 1940260 TI - Twenty-one percent partial hepatectomy. In vivo rat model for the study of liver regeneration. AB - We describe a new model of submaximal stimulation of liver regeneration in the rat. Removal of the right lateral lobes in the rat produced a 21% hepatectomy. The measurement accuracy of the incorporation rate of [14C]thymidine into DNA 24 h after 21% hepatectomy (n = 32) was less than that after the standard 34% hepatectomy (n = 32), with S.D./mean being 35% and 130%, respectively (F-test, p less than 0.025). This model was able to detect regeneration-stimulation activity present in liver cytosol extract and serum of 68% hepatectomized rats. Using this model we identified a subfraction of rat serum achieved after treatment of serum with ethanol and ion-exchange column, which had a highly stimulatory effect. Stimulation obtained with serum from hepatectomized pigs showed that these factors are not species specific. PMID- 1940261 TI - Ultrasound examination in jaundiced patients. Is computer-assisted preclassification helpful? AB - In this study we attempted to determine the diagnostic accuracy and reproducibility of ultrasonography (US) for jaundice and to see how US can best be combined with preliminary clinical-biochemical diagnoses to plan the invasive work-up. US proved reproducible in two diagnostic departments (127 agreements in 135 cases). But, since obstruction was underdiagnosed (15 double-false negatives), the predictive value of a negative result was only 0.83. By adding a term which represents the US conclusion, obstruction or not, to the Copenhagen pocket diagnostic chart score (based on the logistic model) we found that an obstructive conclusion increases the odds of obstruction by a factor of 25, and a non-obstructive conclusion decreases the odds by a factor of only 1.9. We conclude that the preliminary diagnosis is frequently sufficiently certain to be unalterable by US. This leaves only 40% of the jaundice cases in which US is necessary to plan invasive work-up. The US workload can even, it appears, be reduced to about 22% without appreciable penalty in terms of unrewarding invasive procedures. Using these strict indications, four US examinations seem to suffice to avoid one such error. Relying on either US or clinical-biochemical data alone is inferior to the combined strategy. PMID- 1940263 TI - Liver sinusoidal cytotoxic cells are recruited from blood and divide locally. AB - Liver sinusoids contain marginated mononuclear cells which are highly cytotoxic against several tumor cell lines. These cells may play an important role in the elimination of tumor and viral antigens of enteric origin. The question arises whether they are bloodborne, temporarily resident, replacable or permanently resident cells. In order to obtain the answer, a cytogenetic analysis of sex chromosomes in the mononuclear cells from a liver sinusoidal washout of male Lewis rats who had received liver transplants from syngeneic female donors was performed 4 weeks after grafting. About 9% of the liver sinusoidal mononuclear cells obtained from both control and transplanted livers showed mitotic activity, whereas no dividing cells could be found in peripheral blood. In all experiments karyotypic studies of these dividing liver sinusoidal mononuclears from female livers transplanted to syngeneic males revealed in all experiments the male (XY) karyotype. This finding indicates that the cells under study were of blood origin and are not a constitutive cellular component of the liver. They are probably recruited by the liver and divide locally at a signal of a so far unknown origin. PMID- 1940262 TI - Treatment of gallstones with piezoelectric lithotripsy and oral bile acids. A multicenter study. AB - The efficacy of the combination of piezoelectric lithotripsy and oral bile acids in the treatment of gallbladder stones was assessed. Three hundred and sixty three patients with symptomatic radiolucent gallstones in functioning gallbladder were treated in five medical centers using the same protocol with the EDAP LT 01 lithotripter. No anesthesia, analgesia or sedation was used. After one session of lithotripsy, fragmentation was observed in 89% of the patients, and satisfactory fragmentation (fragments less than or equal to 5 mm) in 29%. The satisfactory fragmentation rate was higher in patients with solitary stones less than or equal to 20 mm than in patients with solitary stones 21-35 mm or multiple stones (p less than 0.001). After multiple sessions (mean 1.6 session/patient, range 1-5) the overall rate of satisfactory fragmentation was 50%. After 12 months on oral bile acid therapy, complete clearance of the gallbladder was observed in 69% of patients with solitary stones less than or equal to 20 mm, 25% of patients with solitary stones 21-35 mm and 37% of patients with multiple stones. No complication was observed during the lithotripsy. During follow-up under bile acid therapy, there were five complications (1.4%): four patients had acute cholecystitis and one had mild, self-limited pancreatitis. We conclude that piezoelectric lithotripsy with the EDAP lithotripter is a safe and effective treatment which can be performed in outpatients. Satisfactory fragmentation and rapid disappearance of stones are obtained mainly in patients with solitary stones less than or equal to 20 mm. PMID- 1940264 TI - Maintenance of mixed-function oxidase and conjugation enzyme activities in hepatocyte cultures prepared from normal and diseased human liver. AB - Isolated hepatocytes were prepared from normal and diseased human livers and maintained in primary monolayer culture for up to 96 h. The viability and yields of cell preparations obtained from diseased livers did not differ significantly from those obtained from normal livers. During the culture period a significant increase in cell protein/DNA ratio was observed in both normal and diseased hepatocytes. The maintenance of a number of drug metabolising enzyme activities was determined in these hepatocytes during 96 h of culture. In normal hepatocytes the maintenance pattern of mixed-function oxidase activities (ethoxycoumarin-O deethylase and ethoxyresorufin-O-deethylase) was clearly different from that of the conjugating enzymes (sulfotransferase and glutathione transferase). Whereas ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase activities declined sharply over the first 24 h in culture and then either totally or partially recovered, sulfotransferase and glutathione transferase activities were found to be relatively more stable initially but thereafter decline progressively. In diseased hepatocytes mixed-function oxidase activities were maintained less well than the corresponding activities in normal hepatocytes whereas conjugation enzyme activities were maintained to a similar extent. PMID- 1940265 TI - Effects of ethanol and hepatic vitamin A on the proliferation of lipocytes in regenerating rat liver. AB - The effects of ethanol and hepatic vitamin A on lipocyte proliferation were studied in regenerating rat livers. Positive identification of proliferating lipocytes was achieved by a double immunostaining sequence for cytoplasmic desmin and bromodeoxyuridine-labelled nuclei. Ethanol administration caused a 76 and 36% reduction in labelling indices of lipocytes 2 and 3 days after hepatectomy, respectively, thereby delaying the onset of the proliferative peak of lipocytes by 1 day compared to the control. Hepatic vitamin A did not decrease until 4 days after hepatectomy. The relationship between hepatic vitamin A and lipocyte proliferation was further evaluated in rats fed diets containing four different amounts of vitamin A. Despite the striking differences in liver vitamin A levels, the proliferative activity of lipocytes was unaffected, as measured at the peak of lipocyte proliferation 2 days after hepatectomy. These data indicate that ethanol ingestion suppresses the proliferative response of lipocytes to partial hepatectomy but that this ethanol effect is independent of changes of vitamin A levels in the liver. PMID- 1940266 TI - Recovery of bile secretion following orthotopic liver transplantation. AB - Recovery of hepatic function following orthotopic liver transplantation includes the ability to produce 'adequate' bile. What constitutes adequate bile flow, however, has not previously been defined. The present study was undertaken to characterize biliary water and electrolyte secretion following hepatic transplantation. Bile was sampled from nine liver transplant recipients for 15-25 consecutive days during chronic t-tube biliary drainage. Liver biopsies and t tube cholangiograms were unremarkable in all patients. During the first post operative day mean bile flow, bile salt concentration, [BS], and bile salt output (BSO) were 60.0 microliters/min, 6.8 mM and 0.41 mumol/min, respectively. [BS] increased over days 1-5 and then plateaued at 12.2 mM over days 6-25 post transplant. BSO and bile flow increased over days 1-12 before achieving steady state values of 4.52 mumol/min and 334.7 microliters/min, respectively. In each patient bile flow increased linearly with increasing BSO. Choleretic index (CI), varied from 36.9-77.1 microliters/mumol (mean: 50.7 +/- 8.8). The y-intercept for this relationship ranged from 52.4-156.9 microliters/min (mean: 95.9 +/- 81.8). Only primary bile salts (82% cholate and 17% chenodeoxycholate), were observed in the bile of each patient. Biliary electrolyte concentrations were similar to that observed in plasma. Each was relatively unaffected by changes in bile flow and BSO. Electrolyte outputs increased linearly with respect to both BSO and bile flow. We conclude that recovery of bile secretion following orthotopic liver transplantation occurs gradually over a 10-12 day period and is strongly dependent upon bile salt secretion. PMID- 1940267 TI - Reduction of transmural oesophageal variceal pressure by metoclopramide. AB - In nineteen patients with portal hypertension and oesophageal varices, transmural variceal blood pressure was determined endoscopically by direct puncture of the varices before and after intravenous administration of 20 mg metoclopramide or placebo. No change in pressure was observed after placebo (mean difference -1.3 +/- 24.5%, N.S.), however, metoclopramide reduced the pressure by 17.6 +/- 18.6% (p = 0.02). Our results suggest that metoclopramide may be beneficial for the prevention or treatment of variceal haemorrhage. PMID- 1940269 TI - Detection of HBV-DNA using a digoxigenin-labelled probe. A rapid technique without loss of sensitivity. AB - The sensitivity of four different non-radiolabelled HBV-DNA probes (digoxigenin-, biotin-, acetylaminoflorene-, chemiprobe-labelled) in detecting HBV-DNA were compared with a 32P-labelled HBV-DNA probe using a spot hybridisation assay. Of the non-radiolabelled probes, the probe using digoxigenin labelling was the most sensitive with reliable and reproducible detection to between 1-3 pg HBV-DNA. The use of digoxigenin-labelled HBV-DNA hybridisation assay deserves wider application for the detection of HBV-DNA because of a number of advantages including ease, speed, safety and cost. PMID- 1940268 TI - Identification of PiZ gene products in liver tissue by a monoclonal antibody specific for the Z mutant of alpha 1-antitrypsin. AB - Globular inclusions of abnormal alpha 1-antitrypsin (AAT) in the rough endoplasmic reticulum of hepatocytes is a characteristic feature of AAT deficiency of the PiZ phenotype. It is also seen in some rare M-like Pi types (including M-Cagliari) having low plasma AAT levels and M-like mobility on isoelectric focusing. In this report the ability of a monoclonal antibody (ATZ 11) raised against PiZ hepatocytic AAT to identify AAT inclusions by immunohistochemical techniques is evaluated. The antibody was found to specifically and selectively identify the PiZ gene products in hepatocytes, but not M-Cagliari AAT. Application of the method thus allows distinction of PiZ gene carriers from PiM-like subjects in the absence of serum protein analysis. PMID- 1940270 TI - Recent developments in liver transplantation. Lessons from a 5-year experience. PMID- 1940271 TI - The potential risk of HLA matching after liver transplantation. PMID- 1940272 TI - Beneficial effects of Phyllanthus amarus for chronic hepatitis B, not confirmed. PMID- 1940273 TI - A pseudo-outbreak in a nursing home. PMID- 1940274 TI - Candida species: emerging hospital bloodstream pathogens. PMID- 1940275 TI - Infections and antibiotic use in a community hospital, 1971-1990. AB - OBJECTIVE: To determine the prevalence of infections and antibiotic use at a community hospital in 1990 and to compare the results with those from previous surveys in 1971, 1979, and 1984. DESIGN: Point prevalence survey. SETTING: Community teaching hospital. PATIENTS: All hospitalized patients, excluding those on the nursery, psychiatry, and short-stay wards. INTERVENTION: Medical records were reviewed and a pertinent physical examination was performed on each patient. RESULTS: Overall, 46 (20.1%) of 229 patients had infection in 1990. Community acquired and hospital-acquired infections were present in 26 (11.4%) and 24 (10.5%) of the patients, respectively. The most common site of community-acquired infection was the deep abdomen in 8 (25.8%) of 32 sites, while hospital-acquired infection most frequently involved the lower respiratory tract in 8 (25.0%) of 32 sites. Antimicrobial agents were being administered to 88 (38.4%) of the patients. Cephalosporins (particularly newer, broad-spectrum agents) were the most frequently used antibiotics, comprising 53 (45.3%) of the 117 total antimicrobial prescriptions. Seven (18.4%) of the 38 antibiotics used for surgical prophylaxis were given for more than 48 hours. Trend analysis revealed no significant changes in the proportions of patients with community-acquired, hospital-acquired, or total infection over the last 20 years (p = .18, p = .12, and p = .07, respectively). While the overall use of antibiotics increased (p less than .001), the administration of prophylactic perioperative antibiotics for greater than 48 hours decreased (p = .009). CONCLUSIONS: Despite major shifts in factors associated with an increased risk of infection, the overall prevalences of hospital-acquired and community-acquired infections remained remarkably constant during the last 20 years. Although total antibiotic use increased, the duration of surgical prophylaxis decreased and the pattern of use of therapeutic antibiotics also changed with increased use of broad-spectrum agents. PMID- 1940276 TI - Microbial growth and endotoxin production in the intravenous anesthetic propofol. AB - OBJECTIVE: In this study, we measured microbial growth and endotoxin production in the intravenous anesthetic propofol using 10 different microbial strains; 6 isolated from outbreak cases and 4 from laboratory stock cultures. DESIGN: In each trial, endotoxin-free glass tubes containing 10 ml propofol were inoculated with 10(0)-10(3) CFU/ml of the test organism and incubated at 30 degrees C for 72 hours. SETTING: In May and June 1990, the Centers for Disease Control received reports of 5 outbreaks in 5 states of postsurgical patient infections and/or pyrogenic reactions. Epidemiologic and laboratory investigations implicated extrinsic contamination of an intravenous anesthetic, propofol, as the probable source of these outbreaks. RESULTS: After 24 hours, 9 of the 10 cultures increased in viable counts by 3 to 6 logs. At least 1 ng/ml of endotoxin was produced within 24 hours by Escherichia coli, Enterobacter cloacae, and Acinetobacter calcoaceticus subspecies anitratus. CONCLUSIONS: Propofol can support rapid microbial growth and endotoxin production. To avoid infectious complications, scrupulous aseptic technique should be used when preparing or administering this anesthetic. PMID- 1940278 TI - Ofloxacin. AB - Ofloxacin is a newly licensed fluoroquinolone with an antimicrobial spectrum similar to ciprofloxacin. Compared with ciprofloxacin, the MIC90 values for ofloxacin are lower for S aureus, C trachomatis, and Ureaplasma urealyticum, but somewhat higher against gram-negative bacteria (especially P aeruginosa). Ofloxacin has favorable pharmacokinetics with almost 100% bioavailability; peak serum concentrations obtained one to two hours following oral dosing are higher than those achieved with ciprofloxacin. The oral bioavailability is decreased by the coadministration of antacids, but ofloxacin does not alter serum theophylline concentrations. Ofloxacin has demonstrated bacteriologic and clinical efficacy in the treatment of urinary tract infections, respiratory tract infections, prostatitis, and skin and soft tissue infections caused by susceptible organisms, although there are little data to recommend ofloxacin over ciprofloxacin for these indications. Ofloxacin should not be used alone to treat anaerobic or mixed aerobic/anaerobic infections, and a penicillin or cephalosporin is preferred for known or suspected streptococcal or pneumococcal infection. Ofloxacin is the only quinolone currently approved for the treatment of uncomplicated gonorrhea. It also is effective therapy for nongonococcal urethritis, although the tetracyclines are much less expensive. Ofloxacin has a good safety profile, but, as with other fluoroquinolones, it should not be used in children or in pregnant or nursing women. Further comparative trials may broaden the range of infections that can be treated with ofloxacin. PMID- 1940277 TI - Complications associated with central venous catheters inserted in critically ill neonates. AB - OBJECTIVE: To assess the incidence and spectrum of complications associated with central venous catheter (CVC) placement in the critically ill infant. DESIGN: A prospective study of all babies hospitalized in a neonatal intensive care unit (NICU) from January 1989 to December 1989. Potential risk factors associated with infection were evaluated by a case-control comparison. SETTING: Conducted at a university-affiliated, tertiary care community hospital. PATIENTS: Neonates requiring intensive care and a central venous catheter. Controls consisted of noninfected babies. RESULTS: Of 263 critically ill neonates, only 13 (4.9%) required a CVC insertion. Seventeen CVCs were placed in these 13 neonates for a total duration of 600 days (median, 32 days/cannula). Fifteen (88%) of these cannulas had one or more complications during its catheter life including dislodgement or leakage (53%), occlusion or thrombosis (47%), infections (29%), or minor bleeding (12%). Five babies (29%) developed 6 episodes of bloodstream infection including 3 sporadic cases due to Staphylococcus epidermidis and a cluster of fungemia due to Malassezia furfur associated with lipid emulsion therapy. Infants with a CVC-associated infection were a younger gestational age (24 weeks versus 32 weeks, p = .04) and weighed less at birth (580 g versus 1285 g, p = .02). The overall rate of bloodstream infection was one episode per 100 days of catheter use. CONCLUSIONS: CVCs may be lifesaving to a critically ill neonate, but complications occur frequently. Use must be restricted to infants in whom alternate delivery routes of intravenous therapy or support are otherwise unavailable. PMID- 1940279 TI - Cholera, travel, and infection control. AB - The spread of cholera is a testimony to our inability to provide a consistently decent standard of living to the peoples of the world. Simply separating human sewage from potable water sources would curtail, if not eliminate, the disease. Even persons who acquire cholera would not die if they were given access to rehydration. American travelers should follow sensible food and water precautions, but need not curtail their travels to countries that have cholera. PMID- 1940280 TI - On the evolution of genome size of birds. AB - We measured genome size (nuclear DNA content) by fluorescence flow cytometry in 55 species of birds representing 12 different orders. Similar studies were performed in approximately 100 species by laboratories using absorption cytophotometry of Feulgen-stained nuclei. Although there have been apparent discrepancies in the assigned values for the species used as a reference, the values obtained in the different laboratories are generally in agreement. When the data are standardized in relation to a diploid (2C) value of 2.5 picograms (pg) of DNA for the domestic chicken (Gallus gallus domesticus), the mean for DNA content in 135 species representing 17 orders is 2.82 +/- 0.33 (SD) pg with a range of 2.0-3.8 pg. Thus the genome size of birds is the most conservative of any vertebrate class and, all values considered, is smaller and more uniform in size than previous estimates would indicate. This could be explained by a previously unexplored hypothesis: that the genome of birds has evolved from a small ancestral genome that was reduced before emergence of the protoavian. PMID- 1940282 TI - Polydactyly lethal: a new mutant spontaneously occurring in the FPL strain of rats. AB - A new mutant gene that causes preaxial polydactyly in the hindlimbs was found in the strain of rats with fused pulmonary lobes (fpl). Genetic analysis has revealed that the new mutation is inherited as an autosomal recessive trait and is not closely linked with the fpl gene. Since homozygous mutants die within the first 2 days after birth, the mutant gene was named polydactyly lethal, gene symbol pl. A test for allelism between the pl gene and another gene, pd, which also causes preaxial duplication anomalies, showed no allelism between these two genes. Skeletal examination revealed that all pl/pl newborns had thickening and/or bifurcation of tarsal I and metatarsal I, as well as duplication of the proximal and distal phalanges of digit I in the hindlimbs. In some cases, phalangeal duplication or bifurcation in digit I with thickening of metacarpal I was also found in the forelimbs, although extra forelimb digits were not detected externally. The pl/pl newborns showed hunchback-like abnormal posture externally and had several associated vertebral abnormalities in varying degrees, i.e., kyphosis, scoliosis, splitting of the thoracic vertebral bodies, and fusion of the lumbar vertebral bodies. No major malformations were seen in the visceral organs. The cause of neonatal deaths has not yet been determined. PMID- 1940281 TI - Analytical DNA fingerprinting in lions: parentage, genetic diversity, and kinship. AB - The application of hypervariable minisatellite genomic families to the reconstruction of population genetic structure holds great promise in describing the demographic history and future prospects of free-ranging populations. This potential has not yet been realized due to unforeseen empirical constraints associated with the use of heterologous species probes, to theoretical limitations on the power of the procedure to track genic heterozygosity and kinship, and to the absence of extensive field studies to test genetic predictions. We combine here the technical development of feline-specific VNTR (variable number tandem repeat) families of genetic loci with the long-term demographic and behavioral observations of lion populations of the Serengeti ecosystem in East Africa. Minisatellite variation was used to quantify the extent of genetic variation in several populations that differed in their natural history and levels of inbreeding. Definitive parentage, both maternal and paternal, was assessed for 78 cubs born in 11 lion prides, permitting the assessment of precise genealogical relationships among some 200 lions. The extent of DNA restriction fragment sharing between lions was empirically calibrated with the coefficient of relatedness, r, in two different populations that had distinct demographic histories. The results suggest that reliable estimates of relative genetic diversity, of parentage, and of individual relatedness can be achieved in free-ranging populations, provided the minisatellite family is calibrated in established pedigrees for the species. PMID- 1940283 TI - Mapping the mouse craniofacial mutation first arch (Far) to chromosome 2. AB - First arch (Far) is a semidominant mutation that causes severe craniofacial defects in mice. Here we report the results of linkage studies with the chromosome 2 markers nonagouti, pallid, and Ulnaless. Far is loosely linked to nonagouti (24-37 cM), more closely linked to pallid (13-28 cM), and closely linked to Ulnaless (2.3 +/- 1.5 cM). The embryological defect in Far mutants is confined to one segmentally-derived region of the head, the anterior first branchial arch. It may therefore be significant that, in mapping near Ulnaless, Far also maps in the vicinity of the Hox-4 gene cluster. PMID- 1940284 TI - Occurrence of haploid cells bearing Y chromosomes in bovine embryos fertilized in vitro. AB - Haploid cells bearing Y chromosomes were observed in bovine embryos derived from in vitro fertilization of in vitro-matured follicular oocytes in Japanese Black cattle. The androgenic embryos described in this article might be caused by abnormality in the formation of the female pronucleus. PMID- 1940286 TI - A program to detect linkage between genetic markers and nonadditive quantitative trait loci. PMID- 1940285 TI - Morphological analysis of hair in the hr-2 mutant deer mouse (Peromyscus maniculatus). AB - Skin from 36 hairless deer mice (Peromyscus maniculatus) homozygous for the recessive hr-2 mutation were analyzed for structural defects in hair and hair loss. Comparison of mutant to wild-type hairs demonstrated characteristic abnormalities in cellular organization, hair shape, length, and fragility. Matings between mutants homozygous for the hr-2 gene and for a second mutation producing hairlessness in deer mice, hr-1, showed that these two genes were nonallelic. Structural abnormalities in hairs associated with the expression of this gene suggest that its primary effect may be on the epidermis. PMID- 1940287 TI - Ernest R. Sears (1910-1991): a scientist, a man, a visionary. PMID- 1940288 TI - Video display terminals: potential health effects of office automation. AB - The use of video display terminals (VDTs) has increased dramatically in the past 10 years and is projected to increase. Particular concerns related to the use of VDTs include vision, radiation, reproduction, dermatitis, stress and ergonomics. This article summarizes the current literature related to possible effects of VDT use and health. PMID- 1940289 TI - Neuroimaging of AIDS. AB - A retrospective review of the neuroimaging procedures of 84 patients with the diagnosis of AIDS was performed. Both computed tomography (CT) and magnetic resonance imaging (MRI) procedures were evaluated for the presence of atrophy, enhancing lesions and focal non-enhancing lesions. The imaging findings in several infectious conditions (toxoplasmosis, cytomegalovirus, papovavirus, HIV virus, tuberculosis and histoplasmosis) are described. Intracranial lymphoma, another complication of AIDS, also is discussed. PMID- 1940290 TI - Warts: benign or malignant? AB - The number of identifiable types of human papillomavirus (HPV), based on deoxyribonucleic acid (DNA) sequence, has steadily increased in recent years. Although at one time verruca vulgaris was considered a benign reactive proliferation, current evidence submits that this is not the case; some types of HPV are malignant. PMID- 1940291 TI - Death occurring within one week of cardiac transplantation: findings in eight patients. AB - Between October 1982 and July 1988, 85 patients underwent orthotopic heart transplantation at Methodist Hospital of Indiana. Excluding perioperative deaths, survival rates at six months, one year, two years and three years were 94%, 80%, 74% and 61%, respectively. However, eight patients (9.4%) died within one week of the transplantation. Causes of death included acute failure of the right side of the heart in four patients; compression of the proximal portions of the coronary arteries in one patient; hyperacute rejection in one patient; acute pneumonia and the adult respiratory distress syndrome in one patient; and sudden death of unknown etiology in one patient. The varied causes of death in this group of patients made it inaccurate to assume a particular cause of death for an individual patient, based on the length of the postoperative period alone. We reviewed these eight deaths in detail to better understand and, therefore, reduce the risk of early postoperative death in future patients. PMID- 1940292 TI - Posterior interosseous syndrome. PMID- 1940294 TI - Treatment of chemically dependent physicians. PMID- 1940293 TI - Optometric prescribing becomes law: how did it happen? PMID- 1940295 TI - From the museum. PMID- 1940296 TI - Conservative treatment of genu valgus and varum with medial/lateral heel wedges. AB - Symptomatic bowlegs and knock-knees are common in the aging person and aging athlete secondary to knee trauma. Diagnosis is made by observation and in mild degrees by a standing alignment x-ray that shows narrowing of the joint surface on the appropriate side. The patients complained of pain on the convexity side of the deformity. Treatment consisted of a simple exercise program, non-steroidal anti-inflammatory drugs and appropriate 1/8-inch wedges on the lateral side of the heel for bowlegs or on the medial side of the heel for knock-knees. The effect of a simple heel wedge formed the basis for conservative treatment of symptomatic knee deformities. PMID- 1940297 TI - Surgical myocardial revascularization for the 1990s. AB - After two decades, coronary artery surgery remains a reliable mainstay in the treatment of select patients suffering from ischemic heart disease. However, surgical myocardial revascularization has undergone continuous evolution. Several trends have emerged, including increased use of autogenous artery for bypass conduit, extending indications to include patients with poor ventricular function or following recent myocardial infarction and new techniques, such as surgical angioplasty of the left main coronary artery. PMID- 1940298 TI - Ultrasound and computed tomography-guided percutaneous cholecystostomy. PMID- 1940299 TI - Thymic hyperplasia after chemotherapy: two case reports and a literature review. AB - The development of mediastinal masses in patients previously treated for cancer frequently indicates recurrent or metastatic disease. In this article we describe two patients previously treated for malignancies who had new or recurrent anterior mediastinal masses. These masses proved to be markedly enlarged thymuses due to thymic hyperplasia. The development of thymic hyperplasia after systemic chemotherapy is an uncommon but well known phenomenon. The management of such patients includes close observation or surgical intervention. Empiric antineoplastic therapy is not indicated. PMID- 1940300 TI - Digest of health and medical laws. 1991 Indiana General Assembly. PMID- 1940301 TI - Continuing care contacts. PMID- 1940302 TI - Indiana Medical History Museum. PMID- 1940303 TI - In situ analysis of proteolipid protein gene transcripts during persistent Theiler's virus infection. AB - SJL/J mice inoculated intracranially with the DA strain of Theiler's virus exhibit a persistent demyelinating disease of the central nervous system. To investigate the effect of persistent infection of oligodendrocytes on the expression of myelin genes, we analyzed the level of PLP mRNA in infected as well as uninfected oligodendrocytes. This study was performed at the single-cell level using the simultaneous detection of viral antigens by immunocytochemistry and PLP mRNAs by in situ hybridization with 35S-labeled oligonucleotide probes. Our data indicate that viral infection of oligodendrocytes reduces the level of PLP mRNA by about 80%. PMID- 1940304 TI - Dynamics of Ca2+ transients in norepinephrine-stimulated individual H-35 hepatoma cells: fura-2 digital imaging microscopy and high time-resolution microspectrofluorometry. AB - We investigated spatiotemporal changes in cytoplasmic free Ca2+ concentration ([Ca2+]i) in norepinephrine (NE)-stimulated and fura-2-loaded individual H-35 rat hepatoma cells, using digital imaging microscopy and high time-resolution microspectrofluorometry. Application of NE (5 x 10(-6) M) resulted in an initial transient increase in [Ca2+]i, followed by a small sustained [Ca2+]i plateau above the pre-stimulation level. The initial peak and the small sustained plateau originated from intracellular stores and the extracellular space, respectively. The initial transient evoked by NE was totally blocked by phentolamine, an alpha adrenergic antagonist, but was not blocked by either pre-incubation with nominally Ca(2+)-free medium or by pre-treatment of cells with La3+. On the other hand, the sustained plateau was eliminated by Ca(2+)-free medium or La3+. Therefore, H-35 cells have a Ca(2+)-signaling pathway which is activated via alpha-adrenergic receptors. Mn2+ entered the cytosol after NE stimulation, as shown by quenching of fura-2. This indicates that H-35 hepatoma cells possess Mn(2+)-permeable Ca2+ channels at the plasma membrane. In addition, the Ca2+ efflux pattern from H-35 cells to the extracellular space during NE stimulation was visualized by digital imaging microscopy when free fura-2 was equilibrated between the cells and the extracellular space. The efflux of Ca2+ from H-35 begins between the initial [Ca2+]i transient and the sustained [Ca2+]i plateau. PMID- 1940305 TI - A temporal and ultrastructural relationship between heparan sulfate proteoglycans and AA amyloid in experimental amyloidosis. AB - Previous histochemical studies have suggested a close temporal relationship between the deposition of highly sulfated glycosaminoglycans (GAGs) and amyloid during experimental AA amyloidosis. In the present investigation, we extended these initial observations by using specific immunocytochemical probes to analyze the temporal and ultrastructural relationship between heparan sulfate proteoglycan (HSPG) accumulation and amyloid deposition in a mouse model of AA amyloidosis. Antibodies against the basement membrane-derived HSPG (either protein core or GAG chains) demonstrated a virtually concurrent deposition of HSPGs and amyloid in specific tissue sites regardless of the organ involved (spleen or liver) or the induction protocol used (amyloid enhancing factor + silver nitrate, or daily azocasein injections). Polyclonal antibodies to AA amyloid protein and amyloid P component also demonstrated co-localization to sites of HSPG deposition in amyloid sites, whereas no positive immunostaining was observed in these locales with a polyclonal antibody to the protein core of a dermatan sulfate proteoglycan (known as "decorin"). Immunogold labeling of HSPGs (either protein core or GAG chains) in amyloidotic mouse spleen or liver revealed specific localization of HSPGs to amyloid fibrils. In the liver, heparan sulfate GAGs were also immunolocalized to the lysosomal compartment of hepatocytes and/or Kupffer cells adjacent to sites of amyloid deposition, suggesting that these cells are involved in HSPG production and/or degradation. The close temporal and ultrastructural relationship between HSPGs and AA amyloid further implies an important role for HSPGs during the initial stages of AA amyloidosis. PMID- 1940306 TI - Surfactant protein A is localized at the corners of the pulmonary tubular myelin lattice. AB - Immunogold labeling on sections of a freeze-substituted tubular myelin-enriched fraction isolated from a bronchoalveolar lavage of rat lung showed that surfactant protein A (SP-A) occurs predominantly at the corners of the tubular myelin lattice. Seventy-nine percent of the gold particles were located within 20 nm from a corner. Extracellular SP-A was detected only in the tubular myelin lattice and not in vesicles or secreted lamellar bodies. Ultra-thin cryosections of rat lung fixed in vivo showed that intracellular SP-A was distributed homogeneously over the stacked membranes of lamellar bodies in alveolar Type II cells. The presence of SP-A at the corners of the tubular myelin lattice suggests an important role of this protein in the formation and/or maintenance of this highly ordered lattice. PMID- 1940307 TI - Immunoelectron microscopic evidence for organ differences in the composition of peroxisome-specific membrane polypeptides among three rat organs: liver, kidney, and small intestine. AB - We examined the distribution of peroxisome-specific membrane polypeptides (PMPs) among peroxisomes of the liver, renal cortex, and jejunal mucosa, using antibodies for 70 KD, 26 KD and 22 KD PMPs. Immunoblot analysis showed signals for 70 KD polypeptide in all three kinds of tissue, but for the other two only in the liver and renal cortex, with neither being detected in jejunal mucosa. The total amounts of PMPs increased in all three organs with DEHP (di-(2 ethylhexyl)phthalate) administration. By immunoelectron microscopic analysis using protein A-gold, the three PMPs were localized along the peroxisomal membrane. Quantitation of the gold particles associated with the peroxisomal membrane showed an increase in the density of 70 KD and 26 KD PMPs but a decrease in 22 KD PMP with the administration of DEHP. The presence of tissue-specific localizations of PMPs suggest the 70 KD PMP is a common constituent of peroxisomes of these three tissues, whereas 26 KD and 22 KD PMPs are absent in microperoxisomes of jejunal mucosal epithelium. PMID- 1940308 TI - Thrombospondin: a component of microfibrils in various tissues. AB - We used antisera directed against human platelet thrombospondin (TSP) and microfibril-associated GP 128 to localize the presence of these glycoproteins in fixed sections of human placenta or porcine arteries and skin by immunogold labeling, using electron microscopy. These two antibodies reacted with both human and porcine tissues and always recognized the same structures. In all three tissues the antibodies were associated with the basement membranes and, more precisely, with the microfibrillar structures present at the junction between the basement membrane and the adjacent connective tissue. This localization indicates that GP 128 and TSP are associated with the microfibrils, and suggests their possible role in the attachment of basement membrane to the connective tissue meshwork. Their presence in microfibrils associated with the subendothelial basement membrane in arteries may be important in regard to the thrombogenicity of the subendothelium since, after an endothelial lesion, they may be directly accessible to blood platelets. PMID- 1940310 TI - Immunogold electron microscopy of soluble proteins: localization of Bet v I major allergen in ultra-thin sections of birch pollen after anhydrous fixation techniques. AB - To localize the highly water-soluble major allergen Bet v I in ultra-thin sections of birch pollen, pollen grains were cracked, air-dried, and processed for electron microscopy using one of the following preparation techniques: fixation in aqueous p-formaldehyde + cetylpyridinium chloride; fixation in p formaldehyde vapor; fixation in benzoquinone vapor; inert dehydration; or no fixation. Afterwards the pollen grains were embedded in Lowicryl K4M resin at low temperature. Ultra-thin sections were cut and incubated with a monoclonal antibody against Bet v I, followed by a gold-labeled secondary antibody. In some experiments, commercial rabbit IgG antibodies against birth pollen allergens were also used, followed by incubation with the protein A-gold complex. Bet v I could be localized only after vapor fixation and in the inert dehydrated specimens. Best preservation of ultrastructure and antigenicity was obtained after p formaldehyde vapor fixation. Bet v I antibody binding sites were detected only in the cytoplasmic matrix of the pollen grain, never in the pollen wall. Commercial rabbit antibodies bound to cytoplasm and wall of all prepared specimens, even after aqueous fixation. This might be explained by the assumption that these antibodies recognize a variety of antigenic and allergenic structures, not all of which are so highly soluble as Bet v I. PMID- 1940309 TI - Binding and endocytosis of thrombospondin and thrombospondin fragments in endothelial cell cultures analyzed by cuprolinic blue staining, colloidal gold labeling, and silver enhancement techniques. AB - We investigated the distribution of thrombospondin-specific binding sites and the uptake of thrombospondin-gold conjugates in cultured porcine endothelial cells by light and electron microscopy. Colloidal gold marker and silver enhancement techniques were applied for cytochemical detection of monomeric thrombospondin and fragments of thrombospondin. Thrombospondin binds to granular and fibrillar structures and to sites of cell-cell contact on the cell surface, as indicated by many proteoglycan-cuprolinic blue precipitates. Cell migration tracks on the culture dish bottom are most heavily stained. Labeling of intact thrombospondin and of proteolytic fragments of thrombospondin with colloidal gold followed by silver intensification enables one to detect its binding and uptake in endothelial cells. Binding to the cell surface and uptake of thrombospondin-gold particles was inhibited by heparin but not by hyaluronic acid or chondroitin sulfate. The heparin binding region at the N-terminal end of the thrombospondin molecule proved to be essential for cell surface binding. Gold-conjugated thrombospondin fragments devoid of the heparin binding region were not internalized. After 60 min incubation at 37 degrees C, thrombospondin-gold particles accumulated in the lysosomal compartment close to the nucleus. In the presence of monensin and ammonium chloride, vesicles in this area are swollen and the concentration of particulate marker is reduced. Binding and uptake of thrombospondin by vascular endothelial cells appears to require linkage of the heparin binding region of the thrombospondin molecule to coated pits and heparan sulfate-rich molecules as receptors. Colloidal gold conjugation of thrombospondin fragments proved to be useful for cytochemical characterization of molecular domains. PMID- 1940311 TI - Localization of 17 beta-hydroxysteroid dehydrogenase throughout gestation in human placenta. AB - 17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) is the enzyme responsible for the formation of all sex steroids in gonadal as well as extragonadal tissues. To obtain more information about the age-specific expression of 17 beta-HSD in the human placenta, we have localized this enzyme by immunocytochemistry at the light microscopic level at different periods of gestation. In the 7- and 9-week-old placenta, immunostaining was detected exclusively in the cytoplasm of the syncytiotrophoblast. Between the tenth and thirteenth weeks of gestation, immunolabeling was also observed in the cytoplasm of the cytotrophoblastic cells, suggesting that these cells could be transiently involved in the biosynthesis of sex steroids. Interestingly, between the fourteenth and twenty-fifth weeks of gestation, 17 beta-HSD was observed in both the cytoplasm and nucleus of the syncytiotrophoblast. The reaction product was much more intense in nuclei than in cytoplasm. During the last trimester of gestation, strong immunocytochemical staining was observed in all the nuclei of the syncytiotrophoblast, the cytoplasm being unstained. The meaning of this nuclear staining for 17 beta-HSD is still unclear and remains to be extensively investigated. PMID- 1940312 TI - Antiserum to a novel peptide sequence reacts selectively with epithelial subpopulations. AB - A synthetic peptide corresponding to a novel protein sequence isolated from bovine kidney was used to immunize rabbits. When applied to Western blots of bovine kidney extracts, antiserum to this peptide recognizes proteins with molecular weights of 23 and 18 KD. Immunohistochemical examination of a variety of bovine and rat tissues with this antiserum revealed a unique distribution of immunoreactivity with the intermediate layers of a variety of stratified epithelia, in addition to renal glomeruli. The pattern of reactivity differed from previously described epithelial markers such as cytokeratins. These results indicate that this antiserum may be useful as a tool for the identification of cells of the intermediate layer of stratified epithelia and, as such, may aid in the study of this differentiating/proliferating tissue compartment. PMID- 1940313 TI - Acid phosphatase activity is detected preferentially in the osteoclastic lineage by pre-treatment with cyanuric chloride. AB - We previously reported a simple method to detect osteoid matrices in decalcified bone sections by pre-treatment with cyanuric chloride. We have applied this technique to identify osteoclasts and their precursors in rats. In JB-4 sections prepared from untreated bone tissues with cyanuric chloride, both acid phosphatase (ACP) and tartrate-resistant acid phosphatase (TRAP) were found not only in osteoclasts and bone marrow mononuclear cells but also in osteoblasts. In contrast, treatment of bones with cyanuric chloride resulted in staining ACP preferentially in osteoclasts and mononuclear cells adjacent to the bone surface. In the osteoclasts and most of the ACP-positive mononuclear cells, autoradiography showed calcitonin binding. Decalcification with EDTA did not affect the staining for ACP activity in bones treated with cyanuric chloride. It was possible to simultaneously identify ACP and osteoid matrix in a decalcified section. In soft tissues without treatment with cyanuric chloride, both ACP and TRAP were detected in splenic macrophages, alveolar macrophages, and proximal convoluted ducts in kidney. Neither ACP nor TRAP was found in these cell types in the tissues treated with cyanuric chloride. This procedure provides a new, simple method to identify a more restricted population in the osteoclastic lineage than that detected by TRAP staining. PMID- 1940314 TI - In vitro bromodeoxyuridine labeling of nuclei: application to myotube hybridization. AB - Rat myoblast nuclei were labeled with various concentrations of bromodeoxyuridine (BrdU), an analogue of thymidine, for 24 or 48 hr. Almost every myoblast was labeled with BrdU at concentrations between 10(-7) M and 10(-5) M. When the cells were labeled with 0.5 microM or more, the percentage of labeled cells remained over 90% and 80% at 2 and 5 days, respectively. However, when the cells were labeled with BrdU concentration lower than 10(-7) M the percentage of labeled nuclei decreased more rapidly with time. The BrdU-labeled cells were mixed with an unlabeled population to determine whether their capacity to fuse was reduced. At a BrdU concentration of 0.5 x 10(-6) M, labeled myoblasts fused to a similar extent as unlabeled myoblasts, and a high percentage of marked cells were still perceptively labeled after 5 days. In contrast, the fusion capacity of myoblasts incubated with more than 10(-6) M BrdU was inhibited after only few rounds of DNA synthesis. These myoblasts were eventually able to fuse, however, when the BrdU diminished in the DNA due to cell division. These results indicate that labeling with BrdU at a concentration of 0.5 x 10(-6) M and an incorporation time of 48 hr is optimal to obtain perceptible immunocytochemical staining without affecting myoblast fusion. Such BrdU immunolabeling could be used as a nuclear marker for hybridization studies. PMID- 1940315 TI - Subcellular localization of N-acetylglucosaminide beta 1-4 galactosyltransferase revealed by immunoelectron microscopy. PMID- 1940317 TI - In situ visualization of hemopoietic cell subsets and stromal elements in rat and mouse bone marrow by immunostaining of frozen sections. AB - We have developed a method to section frozen long bones of rat and mouse and stained bone marrow (BM) by (double) immunofluorescence and immunoperoxidase. Here we report this method and reveal the location of early hemopoietic progenitors (Thy-1) and myeloid cells (Mac-1) in mouse BM, and early hemopoietic progenitors and lymphoid cells (Thy-1), erythroid cells (HIS49), and macrophages (ED2) in rat BM. In mouse BM our new findings include (a) the scattered localization of early hemopoietic progenitors (Thy-1low) all over the marrow, and (b) the presence of Thy-1+ stromal cells, mainly subendosteally. In rat BM an important finding is that of (a) a subendosteal region of 12-14 hemopoietic cell layers characterized by an abundance of Thy-1 and the virtual absence of erythroid cells, and (b) the scattering of Thy-1very bright cells which are candidates for the earliest hemopoietic progenitors in this species. The results illustrate that the technique is an excellent tool for studying the topology of BM as an organ of hemopoiesis. PMID- 1940316 TI - Rumenectomy-induced proliferation in duodenal villous epithelium is mechanistically related to the disappearance of statin, a non-proliferation specific nuclear protein. AB - We undertook this study to determine the effect of rumenectomy (a known cause of duodenal crypt cell hyperplasia) on the epithelial growth kinetics of the crypt villus axis in rat duodenum. Ten rats were randomly assigned to control (gastrotomy) and experimental (rumenectomy) groups. After 14 days rats were sacrificed and representative sections were stained with the monoclonal antibody to statin, a non-proliferation-specific protein, by the immunoperoxidase procedure. In the control group, the mean percentages of statin-positive cells in the proximal duodenum, distal duodenum, proximal jejunum, and distal jejunum were 79 +/- 8.5, 79.5 +/- 5.7, 85 +/- 1.4, and 83.5 +/- 0.7, respectively. In the rumenectomy group, statin-positive nuclei were found in the region of the villous apices only, and the corresponding values for the above four areas were 26.2 +/- 4.9, 24.5 +/- 3.5, 31.7 +/- 4.5, and 80.5 +/- 2.1. Except for distal jejunum, the differences in statin expression in the control and experimental groups were significant (p less than 0.001). Rumenectomy leads to the disappearance of statin from the villous column cells of the duodenum and proximal small bowel. The lack of expression of statin in the rumenectomy group documents the potential usefulness of this measure in future studies in neoplasia were understanding of the proliferative status is of crucial importance. PMID- 1940318 TI - Measurement of NADPH-ferrihemoprotein reductase content in sections of liver. AB - We developed a method for measuring the content of NADPH-ferrihemoprotein reductase in sections of liver. First, reductase in sections of rat liver was detected with the indirect immunoperoxidase reaction. Subsequently, specific absorbances were measured in the stained sections by microphotometry. Then, the resulting specific absorbances were converted into the reductase content in the sections using an apparent extinction coefficient obtained from a nitrocellulose binding assay. The average of the reductase content in hepatocytes in periportal, intermediate, and perivenous zones thus measured was consistent with the value in liver homogenates estimated by enzyme-linked immunosorbent assay. Therefore, the present method gave accurate measurement of the reductase content in the sections. Perivenous hepatocytes contained 1.5 times as much reductase (1.15 nmol/g liver, mean for five animals) as that in periportal hepatocytes (0.74 nmol/g liver). The reductase content in hepatocytes in the intermediate zone (0.93 nmol/g liver) was intermediate between values of the periportal and perivenous hepatocytes. PMID- 1940319 TI - Measurement of extracellular space in the rabbit AV node. AB - We used quantitative histochemistry to measure the size of the extracellular space (ESC) in various regions of the rabbit heart. When inulin, sucrose, and sorbitol were used as ECS markers, the ECS of the AV-nodal tissue was found to be, respectively, 2.4, 2.2, and 2.5 times larger than that of left ventricular muscle. Glucose was also measured over a 50-fold serum concentration range as an extracellular marker for AV-nodal tissue, left ventricular muscle, and Purkinje fibers. Measurements with glucose also revealed that the ECS of the AV node was 2.5-2.8 times larger than that of ventricular muscle. In contrast, the ECS of the AV node was the same as that of Purkinje fibers when glucose was used as an extracellular marker. ATP content, measured as an intracellular marker, was similar in both AV-nodal and contractile tissue. Collectively, the data obtained with all extracellular markers indicate that the ECS of the AV-nodal region is approximately 2.5 times larger than that of adjacent contractile tissue. Differences in the size of the ECS in various regions of the heart probably have functional significance and should be considered appropriately during the interpretation of data obtained by biochemical and densitometric approaches. PMID- 1940321 TI - A neonatal secretory protein associated with secretion granule membranes in developing rat salivary glands. AB - In the perinatal submandibular gland, the secretion granules of Type I cells contain protein C (89 KD) and those of Type III cells have Bl-immunoreactive proteins (Bl-IP, 23.5-27.5 KD). In this report we used immunocytochemistry at the light and electron microscopic levels to describe the developmental distribution and localization of protein D (175 KD), which is secreted by both Type I and Type III cells. At its first appearance in Type I cells at 18 days and in Type III cells at 19 days post conception, protein D immunoreactivity (D-IR) is associated with secretion granule membranes; this is more pronounced in Type I than in Type III cells. In early postnatal life the label remains membrane associated, but as Type III cells differentiate into seromucous acinar cells, the lower level of label present in these cells is found in the granule content. Label is found associated with the membrane in secretion granules of Type I cells as long as these cells are identifiable in acini, and subsequent to this similarly labeled cells are seen in intercalated ducts. In the sublingual gland (SLG), D-IR is membrane associated in secretion granules of serous demilune cells, and is present in the secretion granule content in mucous acinar cells. D-IR is also found in the lingual serous (von Ebner's) glands, lacrimal gland, and tracheal glands, primarily in the ducts, where it is localized in the content of secretion granules. PMID- 1940320 TI - Lectin histochemistry of mouse vagina during the estrous cycle. AB - Estrous cycle-related histochemical changes in the vaginal epithelium of sexually mature female mice were studied with 30 fluorescein isothiocyanate (FITC)-labeled lectins. On the basis of the staining pattern the lectins were divided into five groups: I, seventeen lectins that reacted with mucinous surface layer of proestrus. This group comprised two subgroups: Ia, seven lectins that reacted exclusively with the mucinous layer, and Ib, ten lectins that reacted with mucinous cells and the underlying squamous epithelium of proestrus; II, two lectins that reacted with squamous epithelium of proestrus only but were unreactive with mucinous cells; III, three lectins that reacted in a phase specific manner with squamous epithelium; IV, six lectins that showed increased luminal surface reactivity in diestrus and/or metestrus; and V, eleven lectins that were unreactive with vaginal epithelium. These data indicate that the cyclic changes in the morphology of the vaginal epithelium are accompanied by distinct lectin reactivity patterns. PMID- 1940322 TI - Expression of transforming growth factor beta 1 in the submandibular gland of the rat. AB - We employed immunocytochemical and in situ hybridization techniques to study the expression of transforming growth factor beta 1 (TGF-beta 1) in rat submandibular gland. Immunoreactivity for TGF-beta 1 was observed in the cells of granular convoluted tubules (GCTs), striated ducts, and excretory ducts, whereas it was absent in the intercalated ducts and secretory acini in both male and female rats. Immunoelectron microscopy revealed the ultrastructural localization of TGF beta 1 in the secretory granules of GCT cells. On the other hand, signals for rat TGF-beta 1 mRNA were abundant in the GCT and striated duct cells but were lacking in the excretory duct cells. These results provided evidence for the production of TGF-beta 1 in the GCTs and striated ducts of rat submandibular gland. PMID- 1940323 TI - Image cytometry of progesterone receptor expression during the cell cycle in the MCF-7 cell line. AB - Progesterone receptors (PR) appear to be distributed in a heterogeneous way in mammary tumor cells. The study presented here was designed to examine if heterogeneity of PR expression is cell-cycle dependent. Immunofluorescence techniques were used to label PR on the MCF-7 human breast cancer cell line and image cytometry was used to analyze the PR expression during G0 (Ki-67 antigen negative cells), G1, S, and G2/M cell-cycle phases. A second PR, BrdU, and DNA analysis was performed to study PR expression in the S-phase (BrdU-positive cells). Our results show that PR synthesis occurs preferentially during the G0-G1 transition and that PR levels are constant during the G1-G2 transition. The PR expression appears to be cell-cycle related and may therefore explain the heterogeneity of PR expression. However, the possibility that PR heterogeneity may be linked to the existence of PR-negative subclones cannot be ruled out. PMID- 1940324 TI - One-step double immunolabeling of mouse interdigitating reticular cells: simultaneous application of pre-formed complexes of monoclonal rat antibody M1-8 with horseradish peroxidase-linked anti-rat immunoglobulins and of monoclonal mouse anti-Ia antibody with alkaline phosphatase-coupled anti-mouse immunoglobulins. AB - A novel one-step double immunolabeling method was elaborated on the basis of the simultaneous application of preformed molecular complexes of two primary antibodies with their specific secondary antibodies labeled with different enzymes. Treatment with a rat monoclonal antibody (MAb), M1-8, pre-coupled with horseradish peroxidase-linked sheep anti-rat immunoglobulins, and enzyme reaction revealed by the 3-amino-9-ethylcarbazole/hydrogen peroxide reaction, resulted in red-brown intracytoplasmic staining of interdigitating reticular cells in the lymph nodes of Balb/c mice. Another molecular complex, made of mouse anti-Ia MAb with alkaline phosphatase-linked rabbit anti-mouse immunoglobulins, applied at the same time and then developed with naphthol AS-BI-phosphate/fast blue BB as substrate, yielded blue surface staining of this cell type in addition to labeling of B-lymphocytes. The method described provides the possibility of relatively rapid double antigen detection where the binding sites of the secondary antibodies are saturated by the specific primary immunoglobulins. This approach seems to avoid nonspecific binding of primary antibodies to Fc receptors, and the unwanted binding of secondary antibodies with cell surface immunoglobulins on B-lymphocytes or with crossreactive primary antibodies used in the other sequence, if the primary antibodies and the tissue are the same or crossreactive animal species. PMID- 1940325 TI - Application of the FITC-anti-FITC-gold system to ultrastructural localization of antigens. AB - We report the application of a fluorescein isothiocyanate (FITC)-anti-FITC method to localize antigens at the ultrastructural level. In the systems studied, the anti-FITC-based detection method displays high specificity and sensitivity. These observations, combined with ease of production and with availability of FITC protein conjugates, suggest that the FITC-anti-FITC method is a good alternative to presently used methods and is widely applicable to immunochemical and immunocytochemical procedures. The same preparation and protocol can be used for light and electron microscopic studies, thereby reducing possible artifacts introduced if different procedures are used. In the present study, two systems were used to test the method. One system used an FITC-labeled monoclonal antibody (MAb) to schistosome circulating cathodic antigen. In this system, the label was detected in the gut of adult Schistosoma mansoni by an anti-FITC MAb conjugated to 10-nm gold particles. The second system used human IgM antibodies pooled from patients infected with Schistosoma mansoni. In this system detection was accomplished using an anti-human IgM-FITC conjugate followed by the anti-FITC-Au antibody conjugate. PMID- 1940326 TI - Carbon disulfide exposure attenuates adrenergic inotropic response in rats. AB - Catecholamine-induced myocardial necrosis is enhanced in carbon disulfide exposed rats. We investigated whether the reported morphological findings after carbon disulfide exposure are accompanied by functional disturbances of the adrenergic inotropic response as well as by biochemical alterations. The cardiac effects of epinephrine and norepinephrine were studied in urethane-anesthetized rats which had been subacutely exposed to carbon disulfide. Compared with not exposed control animals left ventricular inotropic response was diminished and the transient T-wave elevation of the ECG due to ischemic episodes was enhanced in carbon disulfide-exposed rats. Activity of LDH-isozymes in the myocardium was shifted toward LDH-M. Our results support the hypothesis that carbon disulfide causes disturbances of energy supply in the heart. PMID- 1940327 TI - Environmental health in primary schools in a developing country. AB - In an effort to elucidate the environmental health in developing countries, the environmental and sanitary conditions of Riyadh primary schools were assessed by use of a scoring evaluation sheet for 20 schools representative of primary schools of Riyadh. 20% of schools have been found to be ideally situated and only one fourth of schools with proper building. As regards class rooms, only 25% of them have adequate floor area, window area and are suitably illuminated. Drinking fountains per pupil were inadequate. Overall, environmental rating of 10% excellent, 30% good, and 60% bad were detected in present study. The bad situation of almost two-thirds of primary school buildings in Riyadh is alarming. Remedial suggestion have been forwarded. PMID- 1940328 TI - Schistosomiasis in Cross River State, Nigeria: 1. Prevalence and intensity of infection in Adim, Akamkpa Local Government Area. AB - Mid-stream urine was randomly collected from 248 subjects in Adim. Blood and protein concentrations were determined semi-quantitatively using Combi-7 reagent strips. The urine samples were then processed and any ova of Schistosoma haematobium present were counted per 10 ml urine. Fresh stool samples were also randomly collected, processed and examined for S. masoni and other helminthic ova. The prevalence of S. haematobium in the area was 43.5% and this was found to be age-related but not sex-related. Mean egg count was 137.2 per 10 ml urine. Intense haematuria of 250 ery/microliters and proteinuria of 500 mg/dl accompanied the high egg counts. The stool examination showed no cases of Manson's schistosomiasis but polyparasitism with other intestinal helminths was common particularly among children under 10 years old. This is the first report of urinary schistosomiasis in this area and the high prevalence rate is consistent with the rice farming occupation of the natives of the area. The sensitive nature and the case of application of the reagent strips in determining heavy infections by measuring haematuria and proteinuria is once again confirmed. PMID- 1940329 TI - Transaminases changes and worm burden in multiple infection of Ancylostoma caninum in mice. AB - Aspartate transaminase level was significantly increased in intestine of experimentals that received multiple doses of infection. The level of alanine transaminase rose to a significant value in liver of mice infected with multiple doses. Rise of transaminases is correlated with the necrosis (disruption of intestina) hepatic cells in infected mice. Changes and/or the distribution of aspartate transaminase and alanine transaminase with regard to the dosage is discussed. PMID- 1940330 TI - In vitro antimicrobial efficacy of Centratherum anthelminticum seeds extracts. AB - The in vitro antimicrobial efficacy of different extracts of seeds of Centratherum anthelminticum was studied by the filter paper disk method against several human pathogenic bacteria and fungi. Some of the extracts showed significant effect over tested bacteria and fungi. PMID- 1940331 TI - Lepromatous leprosy in Saudi female from central region. AB - Leprosy is an uncommon disease in Saudi population. Lepromatous leprosy is a most contagious form of leprosy. Erythema nodosum leprosum is an unusual complication of leprosy. We report an unusual case of leprosy from the central region of Saudi Arabia presenting as erythema nodosum leprosum. PMID- 1940332 TI - Long-term yersiniosis surveillance project in Czechoslovakia. AB - The paper presents an epidemiological analysis of 8,232 cases of yersiniosis caused by Y. enterocolitica 03 over 1972-1988 as reported by Hygienic Stations. The steady epidemiological characteristics of yersiniosis were the prevalence of children and boys and a typical seasonal pattern with differences between the Czech and Slovak Republics. In the Czech Republic, there were several incidence peaks following, when summarized, the incidence curve of other alimentary infections, whereas in the Slovak Republic morbidity reached its peak during winter months. The numbers of isolated strains oscillated significantly between districts and by years. It appears that the number of positive findings in different districts is not only an objective value reflecting a mosaic-like pattern of incidence but also depends on the quality of microbiological diagnostics. PMID- 1940333 TI - Comparison of the activity of imipenem and beta-lactams combined with sulbactam and clavulanic acid in beta-lactamase-producing strains of Bacteroides fragilis. AB - We compared the "in vitro" activity of imipenem with 14 beta-lactams, both alone and in combination with clavulanic acid, and sulbactam against 110 beta-lactamase producing strains of Bacteroides fragilis. The following antibiotics were tested: amoxycillin, penicillin, mezlocillin, piperacillin, cephalothin, cephazolin, cefamandole, cefmetazole, cefonicid, cefoxitin, cefotaxime, ceftazidime, ceftizoxime, and ceftriaxone. In all cases, except those of cefoxitin and cefmetazole, these combinations showed a statistically significant increase in beta-lactam activity, which was, however, never higher than that of imipenem, the antibiotic which performed best against Bacteroides fragilis. PMID- 1940334 TI - On the microbiological diagnostics of Campylobacter jejuni. AB - Investigation of campylobacteriosis cases in 1983-1989 resulted in the isolation of a total of 245 antigenically identified and 23 unidentified strains from humans, animals and foods. A commonly accepted method developed in 1985 using our own experience was used for strain isolation and culturing. A variety of nutrient media in combination with different supplementary substances (antibiotics, growth factors) and additives, such as horse serum, were verified as well as filtration and Fortner's procedures. The best results were obtained when material was stored in thioglycolate transport medium accompanied by cold enrichment (24 h at 4 degrees C) and repeated inoculation into appropriate solid nutrient medium. Owing to the simple culturing of C. jejuni, the number of not elucidated diarrheas was reduced and the incidence of campylobacteriosis (approximately 12 %) is higher than that of salmonellosis and shigellosis. A total of 245 C. jejuni strains was classified using Kahlich's antigenic scheme. The incidence of serovars 1 and 2 was greater than 10 %. Five serovars (13, 17, 25, 26 and 27) were represented by only one strain. The study of campylobacteriosis also revealed the long-term excretion of C. jejuni by convalescents (71 days at most) as well as the occurrence of family outbreaks. Procedures were developed to ensure short-term and long-term (freeze-drying) preservation of isolated strains. The number of cases reported by microbiological laboratories in the framework of the Hygienic Service throughout Czechoslovakia suggest an increase in positive findings with C. jejuni as the etiological agent. PMID- 1940336 TI - On the toxinogenicity of Pseudomonas aeruginosa strains. AB - Investigation of 367 P. aeruginosa strains primarily isolated from clinical and other biological material as well as from the environment yielded results suggesting a substantial toxinogenic potential. 92.6% of the assayed culture filtrates derived from the strains under investigation proved positive in the early skin tests on rabbits. 49.7% of the assayed material induced cytotoxic alterations on Vero cells, the rates for Y1 and CHO cells being 50.3% and 43.5% respectively. 54.3% culture filtrates caused haemolysis of rabbit RBC and 52.7% lysed horse RBC. Gelatinase activity was found in 96.3% of tested material, protease in 89.8%, lecithinase in 62.4% and elastase in 29.6%. 12.6% of tested material induced fluid accumulation in a ligated intestinal loop. None of the culture filtrates elicited a positive reaction in the suckling mice test suggesting the absence of the thermostable enterotoxin. PMID- 1940335 TI - Characterization of Campylobacter jejuni strains occurring in the USSR and the Czech Republic. AB - In 1986-1989 the microbiological laboratory in Prague obtained 100 Campylobacter jejuni strains while its counterpart in Moscow gained 120 such strains. The strains were primarily isolated from humans with diarrheal disease, from domestic and wild animals and from the environment. Most C. jejuni strains were successfully specified and classified using a Czechoslovak serotyping scheme proposed by Kahlich. Serotypes 1, 2, 7, 15, 22 and 24 occurred most frequently in the Czech Republic whereas in the Soviet Union the most common serotypes were 7, 16, 5, 2, 1. The proportion of strains which could not be identified in the serotyping scheme was about 10% in the USSR and 20% in the Czech Republic. Our findings suggest differences between the USSR and the Czech Republic in the prevalence and incidence particular serotypes of C. jejuni strains. PMID- 1940337 TI - Inhibition by brefeldin A of the specific B cell antigen presentation to MHC class II-restricted T cells. AB - We have shown previously that specific Ag presentation is prevented by the inhibition of protein synthesis but nonspecific presentation is not. In the present paper, Ag presentation by Ag-specific B cells was examined for sensitivity to brefeldin A (BFA), which blocks protein export from the endoplasmic reticulum. A20-HL B lymphoma expressing surface receptors specific for TNP was used as a B cell, and TNP-OVA was used as a specific Ag. The presence of BFA during pulsing of A20-HL cells with TNP-OVA inhibited the ability of the pulsed cells to stimulate 42-6A T cell clone, specific for OVA323-339 and Iad. The inhibition was not due to nonspecific toxicity of BFA, because the presence of BFA during pulsing of A20-HL cells with OVA323-339 did not affect their APC function. Ag binding to the receptor on A20-HL cells and internalization by the cells were observed in the presence of BFA. Thus, BFA might inhibit intracellular processing of specific Ag or intracellular complex formation of antigenic peptide from specific Ag with MHC class II molecules. Nonspecific Ag presentation by A20 HL cells, however, was resistant to BFA. A20-HL cells pulsed with OVA in the presence of BFA, even after fixation, could stimulate 42-6A cells to produce IL 2, although the IL-2 production was lower than that induced by A20-HL cells pulsed in the absence of BFA. These results suggest that the processing pathways for specific Ag and nonspecific Ag are different from each other, at least partly, in A20-HL cells. PMID- 1940338 TI - Murine cryoglobulinemia: pathogenic and protective IgG3 self-associating antibodies. AB - A murine IgG3 mAb, 6-19, derived from autoimmune MRL-lpr/lpr mice, is a rheumatoid factor (RF) specific for IgG2a and is able to generate cryoglobulins via nonspecific IgG3 Fc-Fc interaction. Intra-peritoneal passive transfer of ascites containing the 6-19 mAb into BALB/c mice induces skin leukocytoclastic vasculitis and acute glomerulonephritis associated with cryoglobulinemia. Because IgG3 interact with each other, we have determined whether noncryoprecipitating IgG3 mAb were able to inhibit the cryoprecipitation of 6-19 mAb and the development of related tissue lesions. In vitro, the cryoprecipitation of 6-19 mAb was almost completely inhibited by a fourfold excess of a noncryoprecipitating non-RF IgG3 (9-106) mAb derived from MRL-lpr/lpr mice. Cryoprecipitation of five other IgG3 mAb was similarly inhibited by the 9-106 mAb, and two other noncryoprecipitating IgG3 mAb, including the 2-6D antinuclear autoantibody, inhibited the cryoprecipitation of 6-19 mAb. In vivo, pretreatment of BALB/c mice with 9-106 or 2-6D mAb prevented the development of skin vasculitis and glomerulonephritis induced by the 6-19 mAb. The cryoglobulin formation was greatly diminished in 9-106 or 2-6D mAb-treated mice, although their serum levels of 6-19 mAb and RF activity were comparable to those of control mice. This indicated that pretreatment with non-cryoglobulin IgG3 inhibited the cryoglobulin generation and cryoglobulin-associated tissue lesions induced by an IgG3 RF cryoglobulin-generating mAb. These results suggest that the balance of formation of IgG3 autoantibodies with or without the cryoglobulin activity may be critical for the development of IgG3 cryoglobulin-mediated tissue lesions in murine lupus, particularly in MRL-lpr/lpr mice. PMID- 1940339 TI - Effects of recombinant transforming growth factor-beta 1 on hematologic recovery after treatment of mice with 5-fluorouracil. AB - Transforming growth factor beta 1 (TGF-beta 1) has been shown to inhibit bone marrow colony formation after in vitro treatment as well as after in vivo administration to normal mice. These data suggest that TGF-beta might either protect, or further depress, progenitor cell levels in mice exposed to a cell cycle-active drug such as 5-fluorouracil (5FU). rTGF-beta 1 was administered repeatedly by either the i.v. or i.p. routes to mice during the hyperproliferative state of the bone marrow that occurs 7 to 9 days after the i.v. administration of 150 mg/kg 5FU. The formation of both multilineage and the more differentiated (CFU-c) colonies was inhibited by 20 to 40%/culture, and 66 to 93%/mouse. When multiple doses of rTGF-beta 1 were administered systemically immediately before the injection of 5FU, the resulting rebound in the number of CFU-c and multilineage colonies containing granulocyte, erythroid, megakaryocyte, and macrophage lineage colonies per culture was markedly inhibited by 30 to 77%, whereas the total number of CFU per mouse was inhibited up to 93%. This effect was maximal when rTGF-beta 1 was administered at daily doses of greater than or equal to 5 micrograms/mouse for at least 3 days. This inhibition of the recovery of the bone marrow from 5FU treatment induced by rTGF-beta 1 was a delayed transient response because by day 16 the progenitor cell numbers and bone marrow cellularity were identical to the 5FU-treated marrow controls. PMID- 1940341 TI - Characterization of a subset of human B lymphocytes interacting with natural killer cells. AB - Tonsil B cells were analyzed for their capacity to interact directly with NK cells in vitro. A specific, direct interaction between NK cells and B cells could be detected by direct conjugation and by cold target inhibition using the B lymphoblastoid cell line BJA.B as a labeled target. The data further suggest that the B cell interaction with NK cells specifically activates the NK effectors and induces their production of IFN-gamma. The NK-interactive population of tonsil B cells were characterized as low-buoyant density cells (by Percoll gradient fractionation) that stained more brightly with Hoechst 33342, both characteristics of activated B cells. Immunofluorescent staining of NK cell-B cell conjugates allowed determination of the cell-surface antigenic phenotype of conjugate-forming B cells. B cell targets were ICAM-1bri, 4F2+, TfR+, CD32+, BB1+, and CD77-. They tended to be CD38-, but overlapped the CD38+ population. No correlation was seen with CD37, CD44, CD75, CD76, HC2, or Ig kappa. This phenotype is most consistent with a late activation stage of differentiation, just before and overlapping the expression of CD38. These B cells do not appear significantly sensitive to NK-mediated cytolysis, suggesting that NK cell cytokine synthesis and secretion (e.g., IFN-gamma) may be more important in the NK cell regulation of the humoral response. PMID- 1940340 TI - Blood transfusion induced changes in cell-mediated lympholysis: to immunize or not to immunize. AB - We have recently observed that the HLA-DR match between recipients and transfusion donors influences the beneficial effect of blood transfusions on allograft survival. To examine the immunologic effects of one-HLA-DR-Ag-matched and completely DR-mismatched transfusions, transfusion-induced changes in cell mediated lympholysis (CML) were investigated. Blood donor directed CTL activity was measured in vitro before and after blood transfusion in 56 candidates for organ transplantation who received planned HLA-typed blood. We report that blood donor-directed CTL activity increased substantially after a single transfusion mismatched with the recipient for two HLA-DR Ag (p less than 0.0001). A transfusion matched for one HLA-DR Ag did not enhance CTL activity. No correlation was found between CTL reactivity and sharing of HLA class I Ag. The present study supports our previous observation that matching for at least one HLA class II Ag (HLA-DR) between transfusion recipient and blood donor is required if immunization by blood transfusion is to be avoided. These data show that the presence or absence of "autologous" HLA-DR Ag on the leucocytes of the transfusion donor plays a decisive rol whether immunization or immune suppression will ensue. PMID- 1940342 TI - The IL-2 receptor alpha-chain alters the binding of IL-2 to the beta-chain. AB - The binding of IL-2 to its high affinity receptor results in the formation of the ternary complex consisting of IL-2, alpha-chain (p55, Tac) and beta-chain (p75). We studied the role of alpha-chain in IL-2 binding to the high affinity receptor using IL-2 analog Lys20 which was made by the substitution of Lys for Asp20 of wild-type rIL-2. Lys20 bound to MT-1 cells solely expressing alpha-chain at low affinity, but did not bind to YT-2C2 cells which solely expressed beta-chain. However, direct binding of radiolabeled Lys20 to ED515-D cells, an HTLV-I infected and IL-2-dependent T cell line, revealed both high affinity and low affinity binding although the Kd value of high affinity binding was 50 to 100 times higher than that of the high affinity binding of wild-type rIL-2. High affinity binding of Lys20 was completely blocked by 2R-B mAb recognizing IL-2R beta-chain. Anti-Tac mAb recognizing IL-2R alpha-chain abolished all of the specific Lys20 bindings. In contrast to the replacement of cell bound 2R-B mAb with wild-type rIL-2 at 37 degrees C, the addition of an excess of Lys20 did not cause the detachment of cell-bound radiolabeled or FITC-labeled 2R-B mAb. Consistent with the results of binding studies, Lys20 induced the proliferation of ED515-D cells, but not large granular lymphocyte leukemic cells. The growth of ED-515D cells was completely suppressed by either anti-Tac mAb or 2R-B mAb. These results strongly suggest that coexpression of the IL-2R alpha- and beta-chains alters the binding affinity of Lys20 and that the interaction between IL-2 and the alpha-chain is a key event in the formation of the IL-2/IL-2R ternary complex. PMID- 1940343 TI - Identification of a cytoplasmic protein kinase regulated by IL-1 that phosphorylates the small heat shock protein, hsp27. AB - IL-1 increases phosphorylation of the small heat shock protein (hsp27) in intact cells. This change was also shown both by introducing [gamma-32P]ATP and Mg2+ into MRC-5 fibroblasts permeabilized by LPC after stimulation by IL-1, and by adding the labeled ATP and Mg2+ to cell extracts. Hsp27 phosphorylated in permeabilized cells or cell extracts was shown by 2D electrophoresis to comprise the three forms seen in metabolically labeled cells, suggesting that the physiologically relevant kinase was acting on the substrate in vitro. Mixing of extracts of resting and IL-1-stimulated cells revealed that stimulated cells contained increased levels of kinase activity that phosphorylated substrate hsp27 in the extracts of resting cells. Existence of the activated kinase was confirmed by showing that extracts of IL-1-stimulated cells phosphorylated purified homogeneous hsp27 at a greater rate than those of resting cells. The kinase activity was maximal in cells stimulated with IL-1 for 5 to 10 min, but had declined to the resting level after stimulation for 40 min. Membrane and cytosolic fractions prepared from cell homogenates both contained hsp27 kinase, but the IL-1-dependent increase was associated with the cytosolic fraction. TNF stimulated cells also contained increased hsp27 kinase activity in the cytosol. The evidence suggests that the cytosolic hsp27 kinase is responsible for the changes in hsp27 phosphorylation induced by the cytokines in intact cells. PMID- 1940344 TI - Differential regulation of human monocyte programmed cell death (apoptosis) by chemotactic factors and pro-inflammatory cytokines. AB - In the absence of appropriate stimuli, monocytes undergo programmed cell death (PCD) or apoptosis. IL-1 beta and TNF-alpha prevent monocyte PCD, which suggests that viability may be regulated by biologically active peptides released during inflammation. To explore this possibility, we evaluated several chemotactic factors and pro-inflammatory cytokines for their ability to regulate PCD. The recruitment factors, FMLP, C fragment C5a, monocyte chemotactic protein-1, or transforming growth factor-beta 1, were incapable of rescuing monocytes from PCD nor did they enhance PCD, whereas several inflammatory cytokines in addition to IL-1 beta and TNF-alpha, including granulocyte-monocyte-CSF and IFN-gamma, prevented monocyte PCD provided that sufficient levels of these cytokines were continuously maintained in the cultures. Cytokine-mediated inhibition of PCD could be blocked by specific antisera, ruling out potential effects caused by LPS contamination. When tested at equivalent concentrations, IL-2, IL-4, and IL-6 had no effect on PCD indicating selectivity in cytokine modulation of monocyte PCD. Because monocytes produce IL-1 beta, TNF-alpha, and granulocyte-monocyte CSF when activated, the data suggest autocrine as well as paracrine control of cell survival and accumulation. The results also suggest that monocytes recruited to a site of inflammation will undergo PCD in the absence of specific cytokines and/or other stimuli that block this process. PMID- 1940345 TI - Characterization of the murine IL-5 receptor complex with the use of a panel of monoclonal antibodies. Relationship to the murine IL-3 receptor. AB - To obtain mAb against the murine IL-5R (mIL-5R), Wistar rats were immunized with B13 cells, a murine Ly-1+ (CD5+) pre-B cell line which is dependent on IL-3 or IL 5 for its growth. A first group of six mAb could immunoprecipitate, from detergent-lysed B13 cells, a 60-kDa polypeptide (p60) corresponding to the recently cloned mIL-5R alpha-chain. A second group of three mAb was able to immunoprecipitate a protein doublet of 130 to 140 kDa (p130 and p140) corresponding to the previously characterized mIL-3R and mIL-3R-like polypeptide, respectively. One mAb (25C9) specifically bound the p130 polypeptide only. Here we show that: 1) mAb directed against the mIL-5R p60 component completely block IL-5 binding; 2) mAb recognizing the p130-p140 doublet interfere with both IL-3 and IL-5 binding; 3) mAb recognizing p130-p140 block the high affinity binding of IL-5 and hence the high affinity mIL-5R consists of the association of the p60 and p130 and/or p140 component; 4) one particular mAb, 25C9, which binds only to the p130 polypeptide, interferes with only IL-3 binding, and has no effect on the binding of IL-5. These results on binding were corroborated by a biologic assay based on the cytokine-dependent proliferation of B13 cells. The results presented here support a model for the mIL-5R consisting of the alpha-chain (p60) associated with the p140 (IL-3R-like), whereas the p130 (IL-3R) is not involved in the IL-5R complex. PMID- 1940346 TI - Characterization of a critical binding site for human polymeric Ig on secretory component. AB - Secretory component (SC) is an integral membrane glycoprotein of secretory epithelial cells which is responsible for the specific transport of polymeric Ig (PIg) to external mucosal surfaces. The ectoplasmic segment which binds polymeric Ig is comprised of five Ig-type domains. Chemically and enzymatically modified forms of the ectoplasmic portion of SC (FSC) were produced and tested for their ability to bind to PIgA and PIgM. Deglycosylated FSC bound specifically to PIg, indicating that N-linked carbohydrate moieties on FSC are not required for binding. Denatured, reduced, and alkylated FSC did not bind to PIgA, and bound to PIgM with significantly reduced affinity, suggesting that native conformation of the polypeptide backbone of SC was important to binding. Tryptic fragments of FSC which bound to PIg were isolated and identified to be derived from domain I of SC. Synthetic peptides comprising overlapping portions of domain I bound to PIg to varying degrees. The strongest affinity was demonstrated by a peptide comprised of residues 15 to 37 of SC. A comparison of the amino acid sequences of human, rabbit, and rat SC indicated that this region contained a high degree of residue identity (78%) and may represent a consensus sequence for binding of FSC to PIg. Importantly, the peptide comprised of residues 15 to 37 was also recognized by a monoclonal antibody, 6G11, which inhibited the binding of FSC to PIgA. These results demonstrate that the binding of human SC to PIg is critically dependent on a highly conserved peptide region within the first domain of SC centering at residues 15-37. PMID- 1940347 TI - Differential expression of Q4 proteins (Qb-1) in fibroblasts and lymphocytes. AB - The Qb-1 protein is coded for by the Q4 gene. This gene appears to be widely transcribed in murine tissues. We have examined the subcellular localization and processing of Qb-1 in fibroblast cells. This protein has previously been reported to be secreted from activated lymphocytes. However, we report that high levels of Qb-1 are present on the surface of B10.P fibroblast cells. We also observed an unusual intracellular distribution for Qb-1. The protein appears to be highly concentrated in the endoplasmic reticulum, in addition to being on the surface. This distribution is not due to inefficient processing. The kinetics of Qb-1 processing and transport are not unusual for class I molecules. Complete resistance to endo-beta-N-acetylglucosaminidase H is acquired, indicating terminal processing. This unusual localization in fibroblast cells and the differential expression of this protein between cell types may reflect a specific role for Qb-1. PMID- 1940348 TI - Glucocorticoids inhibit cytokine-mediated eosinophil survival. AB - Glucocorticoids characteristically induce eosinopenia in vivo and are effective for treating allergic and other eosinophilic disorders. We studied the effect of glucocorticoids on cytokine-induced survival of human eosinophils in vitro. Eosinophils were purified from normal or mildly atopic volunteers by Percoll density gradient and incubated for 4 days in the presence of cytokine plus steroid. Cell viabilities were determined by staining cells with fluorescein diacetate and propidium iodide. In the absence of glucocorticoids, human rIL-5 enhanced eosinophil survival in a dose-dependent manner, from 22 fM for a minimal effect to 2200 fM for maximal effect. When eosinophils were cultured with a submaximal concentration of rIL-5 (220 fM), dexamethasone, methylprednisolone, and hydrocortisone inhibited eosinophil survival in a dose-dependent manner. Inhibition was time-dependent and required at least 2 days' exposure of eosinophils to dexamethasone. Dexamethasone, methylprednisolone, and hydrocortisone at 1000 nM inhibited survival by 88 +/- 2, 66 +/- 9 and 37 +/- 7%. In contrast, estradiol and testosterone (1000 nM) had no effect on eosinophil survival. When eosinophils were incubated with varying concentrations of human rIL-5 and 1000 nM dexamethasone, survival inhibition was reduced at higher concentrations of human rIL-5, and completely abolished by human rIL-5 23,000 fM. Human recombinant granulocyte-macrophage CSF, human rIL-3, and human rIFN-gamma also enhanced eosinophil survival in a dose-dependent manner and dexamethasone (1000 nM) strongly inhibited cell survival when submaximal concentrations of these cytokines were used. The effects of dexamethasone were reversed by higher concentrations of granulocyte-macrophage CSF (10 U/ml) and IL-3 (3 ng/ml). However, even 1000 U/ml IFN-gamma did not overcome dexamethasone inhibition, indicating a difference between the mechanism of eosinophil survival induced by IFN-gamma and other cytokines. These results suggest that glucocorticoids exert a direct, inhibitory effect on eosinophil survival, which may be important in the treatment of allergic and other eosinophilic disorders. Antagonism of this effect by higher amounts of cytokine may be a mechanism for glucocorticoid resistance. PMID- 1940349 TI - Protection of mice from fatal Toxoplasma gondii infection by immunization with p30 antigen in liposomes. AB - Using liposomes as adjuvant, a purified membrane Ag from Toxoplasma gondii (p30) has been tested for its protective effect in mice. Immunization with p30 in liposomes resulted in only one in 15 mice dying from a challenge that killed 11 of 15 control mice (receiving only buffer or liposomes without p30). The p30 Ag alone gave intermediate levels of protection, with 5 of 15 animals dying. The source of the p30 Ag was the rapidly growing, laboratory-adapted strain of T. gondii, RH; challenge was with the recently isolated C strain which still has all the properties of a wild-type strain. To assess the validity of this combination, the amino acid sequence of p30 from these two strains (as predicted from the corresponding gene sequence) was compared and found to differ in only eight residues. This minimal variation argued that RH was a valid source of material for a subunit vaccine, as subsequently confirmed by the protection studies. These results indicate that p30 is an appropriate Ag for development into a subunit vaccine for immunization of humans and/or domestic livestock, which are a major source of human infection. PMID- 1940350 TI - A purified parasite antigen (p30) mediates CD8+ T cell immunity against fatal Toxoplasma gondii infection in mice. AB - Induction of protective immunity against acute and chronic toxoplasmosis can be achieved using p30, the major membrane and excreted/secreted protein of Toxoplasma gondii. This protein, when administered to outbred mice in the presence of the saponin Quil A, is able to induce almost 100% protection against acute infection without evidence of intracerebral cyst development. Adoptive transfer of immune splenocytes from immunized inbred A/J mice conferred a significant level (p less than 0.001) of protection against subsequent challenge. Phenotypic analysis in outbred as well as two different strains of inbred mice (A/J and C57BL/6) demonstrated that CD8+ T cells are selectively stimulated by this immunization protocol. T cell depletion studies using specific mAb directed at either CD3+ or CD8+ T cell phenotype, followed by adoptive transfer, failed to confer protective immunity, whereas CD4+ depletion had no effect. These cytotoxic CD8+ T cells produced high titers of both IFN-gamma and IL-2. Moreover, these CD8+ T cells were directly parasiticidal against radiolabeled extracellular T. gondii, further supporting the critical immune function of these p30 Ag-specific CD8+ T cells in host immunity against T. gondii infection. PMID- 1940351 TI - Influenza A virus infection of macrophages. Enhanced tumor necrosis factor-alpha (TNF-alpha) gene expression and lipopolysaccharide-triggered TNF-alpha release. AB - We have previously shown that infection of macrophages by influenza A virus is capable of priming for a high TNF-alpha production in response to LPS. The present study was designed to examine in more detail TNF-alpha gene expression and TNF-alpha protein release of virus-infected, murine PU5-1.8 macrophages in the presence or absence of low and by itself rather inefficient concentrations of LPS (10 ng/ml). Although influenza A virus infection alone induced a massive TNF alpha mRNA accumulation, translation into the bioactive TNF-alpha protein was low as intra- and extracellularly determined by bioassay, specific ELISA and Western blot. However, when LPS was added simultaneously or up to 4 h after infection, a high TNF-alpha production was initiated. The virus-induced TNF-alpha mRNA accumulation appeared to be due to both transcriptional and post-transcriptional changes: an enhanced TNF-alpha gene transcription as determined by nuclear run-on transcription assay and a markedly prolonged half-life of TNF-alpha mRNA as shown in actinomycin D-treated macrophages. These findings imply that influenza A virus may 1) either directly or indirectly stimulate TNF-alpha gene transcription activators or may interfere with labile transcription repressor proteins and 2) may stabilize TNF-alpha mRNA by delaying its degradation. Both mechanisms, taken together, prime influenza A virus-infected macrophages for a high TNF-alpha release in response to LPS which, as clinical cases show, may adversely affect patients with combined influenza A virus and bacterial infections. PMID- 1940352 TI - Abrogation of tolerance to a chronic viral infection. AB - This study documents failure of peripheral tolerance mechanisms in a chronic viral infection and shows that T cell tolerance to a viral Ag seen as self from fetal life can be broken despite the presence of this Ag in extrathymic tissues. Congenital infection of mice with lymphocytic choriomeningitis virus (LCMV) results in T cell tolerance to the virus. Such mice become carriers for life harboring virus in many tissues including the thymus and exhibit no LCMV-specific CTL responses. Our previous studies have documented the curing of this congenitally acquired chronic infection after adoptive transfer of CD8+ T cells from LCMV-immune mice and the presence of host-derived, LCMV-specific CTL in these "cured" carriers. In this study we have examined the mechanism by which these carriers acquired T cell competence and show that these CTL differentiated from the bone marrow after elimination of viral Ag from the thymus. These results demonstrate that even when a chronic infection has been established in utero, the adult thymus retains the ability to restore immunocompetence to the host and to provide protection against reinfection. Surprisingly, these LCMV specific CTL were acquired at a time when infectious virus and intracellular viral Ag, although cleared from the thymus, were readily detectable in organs such as the kidney, testes, and brain. In fact, active viral replication in peripheral tissues was ongoing when these mice acquired new virus-specific T cells. These results show that clearance of virus form the thymus was sufficient to abrogate tolerance to a congenitally acquired chronic infection and that Ag in peripheral tissues did not tolerize newly developing T cells. These findings suggest that mechanisms that operate on immature cells within the thymus to silence self reactive T cells are effective in induction of tolerance to viruses, but mechanisms of tolerizing mature T cells are likely to breakdown. This has implications for virus-induced autoimmunity and for treatment of chronic infections. PMID- 1940353 TI - A systematic molecular analysis of the T cell-stimulating antigens from Mycobacterium leprae with T cell clones of leprosy patients. Identification of a novel M. leprae HSP 70 fragment by M. leprae-specific T cells. AB - Both protective immunity and immunopathology induced by mycobacteria are dependent on Ag-specific, CD4+ MHC class II-restricted T lymphocytes. The identification of Ag recognized by T cells is fundamental to the understanding of protective and pathologic immunity as well as to the design of effective immunoprophylaxis and immunotherapy strategies. Although some T cell clones are known to respond to recombinant mycobacterial heat shock proteins (hsp) like hsp3 65, the specificity of most T cells has remained unknown. We therefore have undertaken a specificity analysis of 48 well defined Mycobacterium leprae- and/or Mycobacterium tuberculosis-reactive (Th-1-like) T cell clones. Most clones (n = 44) were derived from different leprosy patients, and the remainder from one healthy control. Their HLA restriction molecules were DR2, DR3, DR4, DR5, DR7, DQ, or DP. T cell clones were stimulated with large numbers (n = 20 to 40) of mycobacterial SDS-PAGE-separated fractions bound to nitrocellulose. Each clone recognized a single fraction or peak with a particular Mr range. Some of the clones (n = 7) recognized the fraction that contained the hsp 65 as confirmed with the recombinant Ag. Most clones (n = 41), however, responded to Ag other than the hsp 65. Nine clones responded to a 67- to 80-kDa fraction. Five of them responded also to an ATP-purified, 70-kDa M. leprae protein, but only one of these five (that was HLA-DR2 restricted and cross-reactive with M. tuberculosis) recognized the recombinant C-terminal half (amino acids 278-621) of the M. leprae hsp 70 molecule and also recognized the recombinant M. tuberculosis hsp 70. We therefore have used the 5' part of the M. leprae hsp 70 gene that we have cloned recently. This fragment (that encodes amino acids 6-279) was indeed recognized by the other four M. leprae-specific T cells that were all HLA-DR3 restricted and did not cross-react with the highly homologous (95%) M. tuberculosis hsp 70. These results suggest that this novel fragment is a relevant T cell-stimulating Ag for leprosy patients. A panel of other recombinant Ag, including hsp 18 was tested. The majority of T cell clones appeared to recognize antigenic fractions distinct from hsp. In conclusion, T cells of leprosy patients see a large variety of different Ag including non-hsp, and one newly recognized moiety is the N terminal M. leprae hsp 70 fragment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1940354 TI - The Leishmania donovani lipophosphoglycan T lymphocyte-reactive component is a tightly associated protein complex. AB - Lymphocytes from mice immunized with Leishmania donovani (LPG) were specifically stimulated to proliferate in vitro by purified LPG or its delipidated congener, phosphoglycan. The response was dose dependent and required prior immunization with either LPG or phosphoglycan. Proliferation was eliminated by specific depletion of Thy-1+ cells with antisera and C and the proliferating T cell subset was shown to be CD4+CD8-. Tests of various LPG fragments indicated that the T cell stimulation was associated with the core structure of LPG rather than the lipid or phosphoglycan repeat structure. However, amino acid analysis of LPG and active LPG fragments, after acid hydrolysis, showed the presence of amino acids in peptide linkage. Specific hydrolysis of the glycosidic linkages in LPG with trifluoromethanesulfonic acid provided polypeptide material reactive with two mAb previously believed to be LPG carbohydrate core specific. The protein was separated from LPG by reverse phase chromatography and shown to be a complex of proteins with common epitopes recognized by the two mAb. The dominant species isolated from LPG was a set of small, approximately 11,000 Mr, molecules. Subsequent T cell proliferation studies showed that the lymphocyte stimulation was associated with the protein component of LPG and not the glycan. PMID- 1940355 TI - Enhanced resistance to HIV-1 replication in U937 cells stably transfected with the human IFN-beta gene behind an MHC promoter fragment. AB - Cells of the monocyte lineage act as a major reservoir for HIV, and ways of enhancing the resistance of mononuclear phagocytes to HIV replication would be useful for delaying the onset of AIDS in infected individuals. Seif et al. (J. Virol. 65:664, 1991) have recently shown the possibility of obtaining stable antiviral expression (SAVE), directed against three nonretroviral RNA viruses, and normal cell viability in a significant percentage of murine BALB/c 3T3 cells transformed with an IFN-beta expression plasmid under the control of the 0.6-kb XhoII-NruI promoter region of the murine H-2Kb MHC gene. In the present paper, we show that it is possible to establish SAVE in human promonocytic cells. Cells of the human promonocytic U937 line were stably transfected with a human IFN-beta expression plasmid carrying the neo- and human IFN-beta-coding sequences under the control of the H-2Kb promoter fragment previously used in murine cells. After selection with G418, two transformed clones were isolated that released small amounts of human IFN-beta into the culture medium, without affecting the expression of CD4 and leucocyte function-associated Ag-1 differentiation Ag. The presence of construct-derived IFN-beta mRNA was demonstrated by polymerase chain reaction amplification of cDNA, and the level of 2-5A synthetase, one of the major IFN-induced antiviral proteins, was shown to be constitutively increased. These clones were less permissive for HIV-1 than control clones transformed with the neo gene only. The antiviral state could be modulated by anti-IFN-beta antibodies, in that the continuous presence of antibodies in the culture medium abolished the enhanced resistance to HIV-1 replication, whereas the withdrawal of the antiserum restored the antiviral state, indicating that it did indeed result from the constitutive synthesis of human IFN-beta. These results demonstrate the possibility of restricting HIV-1 replication in human promonocytic cells by establishing SAVE. Further exploration of this method as a possible approach to somatic cell gene therapy of HIV infection appears worthwhile. PMID- 1940356 TI - Human T cell responses to gp63, a surface antigen of Leishmania. AB - gp63, an abundant and conserved leishmania cell surface protein, has been implicated in the ability of these parasitic protozoa to infect macrophages in vitro and has shown potential as a protective immunogen in mice. However, little is known regarding human immune responses to this glycoprotein Ag. In this study, human T lymphocyte responses to Leishmania amazonensis native gp63 and to recombinant gp63 (rgp63) produced in Escherichia coli were evaluated in individuals with active or cured cutaneous, mucosal or visceral leishmaniasis. Both native and rgp63 elicited strong proliferative responses in all patients tested. In addition, IFN-gamma was produced in response to stimulation with both forms of the protein. T cell lines generated from PBMC by stimulation with native or rgp63 were phenotypically similar, and proliferated and produced IFN-gamma in response to stimulation with both forms of the molecule. These results suggest that gp63 is a strong T cell immunogen and that the recombinant and native forms can elicit the same type of T cell response from infected patients. In order to compare the immunogenic properties of these two forms of gp63, PBMC from naive (uninfected) donors were sensitized in vitro with native or rgp63. T cell lines generated against rgp63 proliferated in response to rgp63, but failed to proliferate in response to native gp63 or to promastigote lysate. Thus, rgp63 was effective in eliciting T cell responses from patients with active or cured leishmania infection, but did not effectively induce T cell responses under the conditions used. PMID- 1940357 TI - Transforming growth factor-beta modulates T cell-mediated encephalitis caused by Borna disease virus. Pathogenic importance of CD8+ cells and suppression of antibody formation. AB - Borna disease is a virus-induced, immune-mediated encephalomyelitis based on a delayed-type hypersensitivity reaction. The severity of clinical symptoms after intracerebral infection of rats with Borna disease virus was reduced after treatment with transforming growth factor (TGF-beta 2). Intraperitoneal injection of the recombinant molecule, rTGF-beta 2, started on the day of infection at a dose of either 1 micrograms given every day or every other day for 8 consecutive days or 2 micrograms every third day, was found to result in the absence of typical Borna disease symptoms at 14 days after infection in most of the TGF-beta treated rats, a time point at which all infected control animals not treated with rTGF-beta 2 showed distinct signs of Borna disease. The inhibition of the disease was paralleled by a significant reduction of the inflammatory reaction in the brain. However, the efficacy of treatment with rTGF-beta 2 was transient, because after day 21 only a slight or no reduction of the inflammatory reaction and, consequently, symptoms of Borna disease could be observed. Immunohistologic investigations revealed reduced CD4+ T cell numbers and no changes in macrophage counts in encephalitic lesions of rTG-beta treated rats. However, CD8+ cells were markedly decreased in the encephalitic lesions. Furthermore, the expression of MHC class II Ag was significantly reduced in the brain of rTGF-beta 2 treated Borna disease virus-infected rats, whereas MHC class I Ag expression was not. Most treated animals showed a reduction of Borna disease virus-specific serum antibodies, the result of an inhibition of the IgG response. The results presented here suggest a distinct influence of rTGF-beta 2 on T cell-mediated immune functions during the early phase of Borna disease virus-induced encephalomyelitis. PMID- 1940358 TI - Early changes in cytosolic calcium and membrane potential induced by Actinobacillus actinomycetemcomitans leukotoxin in susceptible and resistant target cells. AB - Actinobacillus actinomycetemcomitans produces a cytolytic peptide leukotoxin which kills susceptible target cells, including human neutrophils, monocytes, lymphocytes, and HL-60 promyelocytic leukemia cells. Cell death occurs as a consequence of colloid osmotic lysis. In the present investigation early leukotoxin-induced changes in membrane permeability were studied by flow cytometry and quantitative spectrofluorimetry in leukotoxin-susceptible and resistant targets. Within 5 s toxin-susceptible cells exhibited concentration dependent, sustained increases in systolic free Ca2+, and this was rapidly followed by a progressive fall in membrane potential. These early manifestations of membrane injury occurred approximately 10-15 min before cell death, as reflected by flow cytometric analysis of propidium iodide stained cells. The rise in cytosolic Ca2+ was almost entirely due to an influx of extracellular Ca2+. The results of Hill plots for the action of leukotoxin on Ca2+ permeability in human neutrophils or HL-60 cells suggested that two or more toxin molecules participate in the assembly of an ion conducting pore in the plasma membrane. Changes in membrane permeability or cell viability were not observed in response to heat inactivated toxin. Under appropriate conditions toxin-induced membrane abnormalities were inhibited by leukotoxin-neutralizing mAb or relatively high concentrations (greater than or equal to 2.5 mM) of extracellular Ca2+. Leukotoxin-resistant target cells showed no evidence of membrane injury even when exposed to high concentrations of leukotoxin for prolonged periods of time. These included resistant human K562 erythroleukemia cells and murine SP2 myeloma cells which have previously been shown to adsorb the toxin, suggesting that they possess a protective mechanism(s) which impedes toxin insertion or assembly in the lipid bilayer. These data support the concept that A. actinomycetemcomitans leukotoxin acts as a cell-specific, pore-forming protein which permeabilizes the plasma membrane of susceptible target cells. PMID- 1940359 TI - Transcriptional regulation of cytokine genes in nontransformed T cells. Apparent constitutive signals in run-on assays can be caused by repeat sequences. AB - Cytokines are immunoregulatory proteins that are secreted by T lymphocytes and other cells upon activation. A controversy exists as to whether the induction of cytokine production is mediated at the transcriptional level by the initiation of RNA synthesis or at the post-transcriptional level by the enhancement of mRNA stability. We show that in a nontransformed T cell clone the induction of all of the cytokines that are analyzed in this report is mediated transcriptionally. We also found that a constitutive signal was seen in resting cells when the probes used in the nuclear run-on assay contained some potential cross-hybridizing sequences, for example a poly (A) tract in a cDNA probe. This observation could explain the constitutive signals seen in other studies that claim cytokine production is regulated by differential mRNA stability. PMID- 1940360 TI - Expression of antibody Fab domains on bacteriophage surfaces. Potential use for antibody selection. AB - We describe a method for expressing an antibody Fab fragment on the surface of M13 filamentous bacteriophage. The L chain gene, preceded by an Escherichia coli signal sequence, is linked to the 5' end of the gene for the M13 major coat protein. A partial H chain gene, preceded by an E. coli signal sequence and truncated at the end of the CH1 region, is inserted on a plasmid adjacent to the fused L chain gene, so both genes are under the transcriptional control of an inducible promoter. The plasmid also contains the M13 origin of replication. When the promoter is induced, functional antibody Fab fragment appears on the surface of the E. coli inner membrane, as shown by specific binding to an Ag-affinity matrix. When the E. coli are further infected with a helper phage, allowing replication and packaging of the plasmid into phage particles, the resulting phage specifically bind to an Ag-coated plate, indicating they have antibody Fab fragment on their surface. The antibody-expressing phage can also be specifically bound to and eluted from an Ag-affinity column. These observations support the possibility of a new way of generating antibodies, in which amplified Ig cDNA from an appropriate B cell population is cloned into a suitable M13 vector, and phage containing the genes for desired antibodies are selected directly by binding to an Ag-affinity matrix. PMID- 1940361 TI - Structural basis of a conserved idiotope expressed by an autoreactive human B cell lymphoma. Evidence that a VH CDR3 mutation alters idiotypy and specificity. AB - Our laboratory has previously investigated the relationship of autoimmune disease and B cell neoplasia in a patient with a diffuse, well differentiated splenic B cell lymphoma and associated autoimmune hemolysis due to an anti-Pr2 antibody. EBV-immortalized B cell clones, established from this lymphoma, were shown to secrete the same pathologic anti-Pr2 antibody. The antiidiotypic mAb, RI.1, defined a private Id (IdRI.1) of the anti-Pr2 antibody that was related to the Ag binding site and was expressed by both the lymphoma and derived cell lines. This unique Id was expressed by the majority of splenic tumor B cells and also was conserved over a period of 4 yr. In this report, the structural basis of IdRI.1 expression was investigated by analysis of Id- variants isolated by flow microfluorimetry using RI.1. Six Id- cell lines that secrete IgM kappa but lack Pr2 specificity were generated from an Id+ cell line, LS2. These lines were shown to be related to LS2 and the lymphoma by karyotype and by restriction fragment analysis of Ig gene rearrangements. Shared and unshared nucleotide substitutions in the VH and VL regions of the six independent clones were used to construct a genealogic tree relating the Id- clonal members to a common Id+ precursor. The tree illustrates that the base changes occurred sequentially, suggesting that they were introduced by somatic point mutation. Only one VH CDR3 bp difference from the LS2 nucleic acid sequence is common to all Id- sequences, resulting in an amino acid substitution of cysteine 108 to tyrosine. Taken together, these findings suggest that both the expression of IdRI.1 and Ag binding are affected by a single mutation localized to the D region of the anti-Pr2 antibody. PMID- 1940362 TI - Comparative studies of the cytotoxic T lymphocyte-mediated cytotoxicity and of extracellular ATP-induced cell lysis. Different requirements in extracellular Mg2+ and pH. AB - We recently proposed that extracellular ATP (ATPo) may be involved in CTL mediated cytotoxicity by acting in concert with yet unidentified cellular components (ATPo receptors/ATPo-binding proteins, ectoprotein kinases). The TCR triggered ATPo accumulation by CTL has been demonstrated, whereas the resistance of CTL to ATPo was explained by the action of highly active ecto-ATPases or by the absence of relevant ATP-binding proteins. However, no data were available to discriminate between the possibilities of: i) ATPo acting alone as a "hit" molecule because of the cell-permeabilizing properties of ATP4- or ii) ATPo acting as a "messenger" (as MgATP2-) in concert with other molecules. Comparing ATPo-induced and CTL-mediated cell lysis, we found that ATPo-induced lysis of some target cells is greatly decreased at neutral and acidic pH, whereas Ca(2+) dependent CTL-mediated lysis of the same cells is barely affected. In agreement with the observed pH dependency, at low Mg2+ concentrations, which favor ATP4- over MgATP2-, maximal ATPo-induced lysis was observed. However, CTL-mediated cytotoxicity in both Ag-specific and retargeting assays was markedly reduced at low Mg2+ concentrations. These results suggest that ATPo acting alone as a "hit" molecule cannot fully account for the extracellular Ca(2+)-dependent lethal hit delivery by CTL or that ATP4- is active at very low concentrations. This conclusion was further supported by studying the lytic effect of ATPo and CTL on the anti-TCR mAb-coupled SRBC. CTL were efficient in the SRBC lysis, whereas no lysis of SRBC by ATPo was detected. The resistance of SRBC to ATPo is not caused by a high ATPo degradation, because the ecto-ATPase activity of SRBC was much lower than in ATPo-resistant CTL OE4 cells and comparable with EL4 tumor cells, which were easily lysed by ATPo. These data suggested the need for careful consideration of the pH and cation composition of the media used for studying ATPo effects. The caveats in the use of ATP-degrading enzymes to implicate the role of extracellular ATPo in the CTL-mediated cytotoxicity are described here. A clarification of the previously described cytotoxicity inhibition by hexokinase, which is caused by an inhibitory salt effect, is presented. It is suggested that if Ca(2+)-dependent lysis of SRBC and of other target cells by CTL does involve extracellular ATP, it may function as a "messenger" in concert with other extracellular molecules.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1940363 TI - Immunogenicity of human T cell leukemia virus type-I (HTLV-I) antigens for cytotoxic T lymphocytes in the rat system. AB - We showed previously that WKA (rat MHC, RT-1k) and DA (RT-1a) rat CTL specific for human T cell leukemia virus type-I (HTLV-I) recognized the gag and pX gene encoded Ag. In the present study, we explored HTLV-I Ag recognized by CTL from other MHC genotype (RT-1l) rats, LEW and F344, and examined whether HTLV-I Ag expressed by recombinant vaccinia viruses (rVV) could prime WKA and LEW rats for HTLV-I-specific CTL. Upon priming in vivo and repetitive stimulation in vitro with HTLV-I+ syngeneic T cells, HTLV-I-specific CD8+ CTL were demonstrated in LEW and F344 rat spleen cell cultures. Interestingly, these CTL were directed against HTLV-I env and pX gene products. Immunization of LEW and WKA rats with the env and gag gene-expressing rVV, respectively, resulted in generation of HTLV-I specific CD8+ CTL. However, a pX-gene expressing rVV failed to prime either rat strain. In addition, HTLV-I-specific CD8+ CTL from F1 hybrid (WKA x LEW) rats generated by immunization and restimulation with HTLV-I+ syngeneic T cells showed gag and pX Ag specificity on WKA rat cells and env and pX Ag specificity on LEW rat cells. These results suggest that immunogenicity of HTLV-I gag and env Ag in induction of HTLV-I-specific CTL varies depending on MHC, and that the pX Ag expressed by rVV is not a potent immunogen for rats. PMID- 1940364 TI - Stability changes in pim-1 proto-oncogene mRNA after mitogen stimulation of normal lymphocytes. AB - mRNA expression of the serine/threonine kinase protooncogene Pim-1 was investigated in mitogen-treated normal bovine lymphocytes. After stimulation with Con A and phorbol ester (PMA), normal bovine PBMC exhibited a 3.5-fold induction of pim-1 mRNA within 4 h of stimulation. By 17 h poststimulation, however, the level of pim-1 mRNA had fallen to approximately 50%. Similar transient kinetics of pim-1 expression were also observed in mitogen-stimulated bovine lymph node lymphocytes and the amount of pim-1 mRNA induced was dependent on the type of mitogen stimulus. Typically, stimulation with Con A and PMA together acted synergistically resulting in a greatly increased amount of pim-1 mRNA induction compared to stimulation with either Con A or PMA alone. To determine if an increase in pim-1 mRNA stability contributed to the overall increase in pim-1 mRNA levels observed after mitogen stimulation, RNA half-life studies were performed. At 4 h poststimulation, pim-1 mRNA in bovine lymph node lymphocytes was relatively stable with a t1/2 of approximately 80 min; at 17 h poststimulation, however, the t1/2 (approximately 35 min) was markedly decreased. In addition, cyclohexamide treatment was found to markedly increase the stability of pim-1 transcripts in bovine PBMC suggesting that a protein synthesis-dependent posttranscriptional pim-1 mRNA degradation pathway may be involved in the regulation of pim-1 mRNA levels in lymphoid cells. To investigate the possible contribution of the destabilizing (UAUU)n motif to pim-1 mRNA stability, the t1/2 of the short 2.4-kb germ cell-specific pim-1 transcript found in rat testes was compared to that of the longer 2.8-kb somatic transcript expressed in stimulated rat lymphocytes. t1/2 determination experiments showed that the 2.4-kb testes specific transcript, which is missing the destabilizing (UAUU)n sequence, was quite stable (t1/2 much greater than 6 h). In contrast, the t1/2 of the longer 2.8 kb somatic cell pim-1 transcript that contains this A/U-rich sequence motif was found to be much shorter (t1/2 approximately 130 min) in mitogen-activated rat lymphocytes. Together these findings indicate that the transient induction of pim-1 gene expression is associated with normal lymphocyte activation and that the stability of pim-1 transcripts is regulated in lymphocytes during the course of activation. In addition, the differences in pim-1 mRNA stability observed in germ cells and lymphocytes of the same animal are likely the result of molecular mechanisms involving differential regulation by the message destabilizing (UAUU)n motif. PMID- 1940365 TI - Differential stability of antigenic MHC class I-restricted synthetic peptides. AB - Various synthetic peptides recognized as Ag by CTL in the context of MHC class I molecules were tested for stability in vitro and in vivo. Peptide inactivation in vitro was quantitated by titrating the amount of peptide required to sensitize target cells for lysis by specific CTL clones. The degree of inactivation after overnight incubation at 37 degrees C varied widely among a series of antigenic peptides. Some were nearly unaffected, whereas others lost activity by more than 100-fold or even 10,000-fold. However, no correlation was found between susceptibility to serum inactivation and antigenic potency as measured in short term cytolytic assays. No inactivation occurred at 4 degrees C, or at 37 degrees C in the absence of serum, under the conditions used. Serum inactivation most likely involved proteolysis because it could be inhibited by protease inhibitors. Moreover, presumed cleavage products of a radiolabeled susceptible peptide could be visualized by TLC. In vivo, the persistence of the antigenic activity of the injected peptides, either in extracellular fluids or on tumor target cells growing in an ascites form, correlated with the degree of stability found for the peptides in vitro. The differential stability of synthetic peptides may have important consequences for attempts to manipulate the development of an immune response in vivo. PMID- 1940366 TI - IgE and IgG binding of peptides expressed from fragments of cDNA encoding the major house dust mite allergen Der p I. AB - Large peptides expressed from cDNA fragments of a clone encoding the mite allergen Der p I were able to bind IgE and IgG in sera from allergic individuals. The binding was found for peptides from sequences throughout the molecule, with at least five regions, comprising residues 1-56, 53-99, 98-140, 166-194, and 188 222. The only limitation was that more than 30 amino acid residues were required for consistent binding. Each of seven sera examined showed a different profile of antibody binding to the peptides. For the most part the pattern of IgE and IgG binding to the peptides for each serum was similar, demonstrating a concordant repertoire. In 5/7 sera, however, IgG bound to some peptides which had little or no IgE binding activity, thus showing more diverse specificities. It is suggested that some divergence of repertoire can develop during the maturation of the B cell response. PMID- 1940367 TI - Prolactin influences autoimmune disease activity in the female B/W mouse. AB - Prolactin, an anterior pituitary hormone, stimulates humoral and cell-mediated immunity. This study investigated effects of manipulating prolactin levels in the autoimmune B/W mouse model of SLE. A group of B/W females was treated with daily injections of the prolactin-suppressing drug, bromocriptine. These mice had delayed elevation of anti-DNA antibodies and serum IgG; longevity was increased compared to control mice. Functioning syngeneic pituitary glands, implanted under the renal capsule, produced prolonged hyperprolactinemia in a separate group of female B/W mice. Hyperprolactinemic animals were characterized by premature albuminuria, elevated circulating gp70IC and IgG, and accelerated mortality. Analyses of thymic and splenic lymphocytes revealed no differences in lymphocyte subpopulations in mice with altered prolactin levels. This is the first report to substantiate an immunomodulatory role for prolactin in B/W mice. Further evaluation of this model may identify specific means of intervening clinically with immunosuppressive hormone-modulating therapy in SLE. PMID- 1940368 TI - IL-4 inhibits the costimulatory activity of IL-2 or picolinic acid but not of lipopolysaccharide on IFN-gamma-treated macrophages. AB - We reported previously that IL-2 induces tumoricidal activity in IFN-gamma treated murine macrophages. The present study was performed to investigate the regulation of IL-2-dependent tumoricidal activity in murine macrophage cell lines. The v-raf/v-myc-immortalized murine macrophage cell lines ANA-1, GG2EE, and HEN-CV did not express constitutive levels of cytotoxic activity against P815 mastocytoma cells. Moreover, these macrophage cell lines did not become tumoricidal after exposure to IL-4, IFN-gamma, IL-2 or LPS. However, these macrophages developed cytotoxic capabilities after incubation with either IFN gamma plus IL-2 or IFN-gamma plus LPS. IL-4 inhibited IFN-gamma plus IL-2- but not IFN-gamma plus LPS-induced tumoricidal activity. This effect of IL-4 was not restricted to v-raf/v-myc-immortalized macrophage cell lines because similar results were obtained by using a macrophage cell line that was established from a spontaneous histiocytic sarcoma. The suppressive activity of IL-4 on the ANA-1 macrophage cell line was dose-dependent (approximately 12-200 U/ml) and was neutralized by the addition of anti-IL-4 mAb. IL-4 decreased the IFN-gamma induced expression of mRNA for the p55 (alpha) subunit of the IL-2R in ANA-1 macrophages. Therefore, at least one mechanism by which IL-4 may have inhibited IFN-gamma plus IL-2-induced tumoricidal activity was by reducing macrophage IL-2R alpha mRNA expression. We have previously reported that picolinic acid, a tryptophan metabolite, is a costimulator of macrophage tumoricidal activity. We now report that IL-4 also inhibited IFN-gamma plus picolinic acid-induced cytotoxicity in ANA-1 macrophages. We propose that IL-2 and picolinic acid may have a common mechanism of action that is susceptible to IL-4 suppression. PMID- 1940369 TI - IL-10 inhibits cytokine production by activated macrophages. AB - IL-10 inhibits the ability of macrophage but not B cell APC to stimulate cytokine synthesis by Th1 T cell clones. In this study we have examined the direct effects of IL-10 on both macrophage cell lines and normal peritoneal macrophages. LPS (or LPS and IFN-gamma)-induced production of IL-1, IL-6, and TNF-alpha proteins was significantly inhibited by IL-10 in two macrophage cell lines. Furthermore, IL-10 appears to be a more potent inhibitor of monokine synthesis than IL-4 when added at similar concentrations. LPS or LPS- and IFN-gamma-induced expression of IL-1 alpha, IL-6, or TNF-alpha mRNA was also inhibited by IL-10 as shown by semiquantitative polymerase chain reaction or Northern blot analysis. Inhibition of LPS-induced IL-6 secretion by IL-10 was less marked in FACS-purified peritoneal macrophages than in the macrophage cell lines. However, IL-6 production by peritoneal macrophages was enhanced by addition of anti-IL-10 antibodies, implying the presence in these cultures of endogenous IL-10, which results in an intrinsic reduction of monokine synthesis after LPS activation. Consistent with this proposal, LPS-stimulated peritoneal macrophages were shown to directly produce IL-10 detectable by ELISA. Furthermore, IFN-gamma was found to enhance IL-6 production by LPS-stimulated peritoneal macrophages, and this could be explained by its suppression of IL-10 production by this same population of cells. In addition to its effects on monokine synthesis, IL-10 also induces a significant change in morphology in IFN-gamma-stimulated peritoneal macrophages. The potent action of IL-10 on the macrophage, particularly at the level of monokine production, supports an important role for this cytokine not only in the regulation of T cell responses but also in acute inflammatory responses. PMID- 1940370 TI - IL-4 promotes anti-Ig-mediated protein kinase C translocation and reverses phorbol ester-mediated protein kinase C down-regulation in murine B cells. AB - Co-stimulation of B lymphocytes with IL-4 plus nonmitogenic concentrations of anti-Ig antibodies, or protein kinase C (PKC) activators, drives resting B cells into DNA synthesis. Although cross-linking of the sIg receptors provokes the generation of the intracellular second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol, the molecular mechanism utilized by IL-4R in murine B cells has not, as yet, been defined. In human B cells IL-4 has been shown to induce a transient rise in IP3 followed by a sustained elevation of cAMP. However, in murine B cells, IL-4 does not induce the release of IP3, Ca2+ mobilization, PKC translocation, or indeed modify signaling via the phosphoinositide pathway induced by ligation of sIg receptors. We now present evidence that, in murine B cells, IL-4 synergizes with nonmitogenic concentrations of anti-Ig to provoke translocation of PKC from the cytosol to membranes. In addition, the lymphokine up-regulates PKC levels and activity and prevents phorbol ester-induced PKC down-regulation in B cells. We therefore propose that (unknown) signals generated via IL-4R potentiate and/or prolong sIg induced PKC activation. These observations may therefore provide a biochemical basis for explaining how IL-4 and anti-Ig synergize to induce B cell activation. PMID- 1940371 TI - IL-3 and IL-5 prime normal human eosinophils to produce leukotriene C4 in response to soluble agonists. AB - Eosinophils (Eos) produce large amounts of leukotriene C4 (LTC4) and platelet activating factor (PAF) in response to calcium ionophore. However, the capacity of naturally occurring soluble agonists to promote lipid mediator formation by Eos is largely unknown. Our previous studies on neutrophils and basophils showed that certain hematopoietic growth factors are important regulators of lipid mediator formation. We examined LTC4 production by normal human Eos from healthy donors in response to soluble agonists with or without preincubation with the cytokines IL-3 and IL-5. Among three agonists (FMLP, C5a, PAF) tested over a wide concentration range, only FMLP induced some LTC4 formation by itself in normal Eos. However, after preincubation with IL-3 or IL-5, Eos produced detectable amounts of LTC4 in response to all three agonists. Eos primed by IL-3 or IL-5 generated at least 1 order of magnitude more LTC4 in response to FMLP as compared to C5a or PAF. FMLP-induced LTC4 production was enhanced by 26 to 635% (n = 16) and 67 to 611% (n = 12) after preincubation with IL-3 or IL-5, respectively. Priming for LTC4 production was concentration dependent occurring at IL-3 or IL-5 concentrations of 3 to 30 ng/ml and required an optimal preincubation period of 90 min. Thus, IL-3 and IL-5 profoundly modulate the production of lipid mediators by Eos in response to the soluble agonists FMLP, C5a, and PAF. Our data further support the importance of these cytokines in inflammatory reactions involving Eos. PMID- 1940372 TI - Inactivation of recombinant human tumor necrosis factor-alpha by proteolytic enzymes released from stimulated human neutrophils. AB - Activated human neutrophils (PMN) degrade rTNF-alpha resulting in a loss of cytotoxic activity against murine L-929 cells (L cells). This inactivation is mediated through proteases released from activated PMN. Exposure of TNF to H2O2, glucose oxidase, xanthine oxidase, or myeloper-oxidase-H2O2-halide did not affect TNF cytotoxicity for L cells. Exposure to trypsin, chymotrypsin, pronase E, or elastase, however, did diminish TNF bioactivity. FMLP-stimulated PMN in the presence, but not in the absence, of cytochalasin B reduced TNF activity, whereas PMA-stimulated PMN did not affect TNF. Stimulation of PMN with opsonized bacteria also induced TNF inactivation as well as the supernatant of FMLP-stimulated cells. Addition of protease inhibitors to the FMLP-stimulated cytochalasin B treated PMN abrogated the inactivation of TNF cytotoxicity for L cells, whereas scavengers were not protective. In addition, PMN from a chronic granulomatous disease patient also decreased TNF bioactivity. Inactivation of TNF by activated PMN correlated with granule release and not with superoxide production. Exposure of TNF to proteases and FMLP-activated PMN also resulted in a loss of reactivity with anti-TNF antibodies, as measured by ELISA, and in the formation of an approximately 10-kDa split product from the 17-kDa rTNF molecule. Partial degradation of TNF by proteases released from activated PMN may result in a diminished TNF bioactivity and thereby contribute to the regulation of local inflammatory reactions. PMID- 1940373 TI - Staphylococcal toxins bind to different sites on HLA-DR. AB - Staphylococcal enterotoxins (SE) and toxic shock syndrome toxin 1 (TSST-1) bind to MHC class II molecules and the toxin-class II complexes induce proliferation of T cells bearing specific V beta sequences. We have previously reported that these toxins display varying binding affinities for HLA-DR1. We now investigated whether these differences simply reflected differences in binding affinity for a single class II binding site or, at least in part, the engagement of different binding sites on the HLA-DR complex. Through competitive binding studies we show that SEB and TSST-1, which are not closely related by their amino acid sequences, bind to two different sites on HLA-DR. Both of these sites are also occupied by staphylococcal enterotoxin A (SEA), enterotoxin D (SED), and enterotoxin E (SEE) which exhibit more than 70% amino acid sequence homology. SEB and TSST-1 failed to inhibit SEA binding to HLA-DR. These studies suggest that there may be three distinct, although perhaps overlapping, binding sites on HLA-DR for these toxins. Further, although SED and SEE are similar to SEA in structure, and appear to bind the same sites on HLA-DR as SEA, they displayed significantly lower binding affinities. T cell proliferative responses to SED required a higher concentration of the toxin than SEA, probably reflecting its lower binding affinity. SEE, however, elicited T cell responses at very low concentrations, similar to SEA, despite its much lower binding affinity. Therefore, although the affinities of these toxins to MHC class II molecules appear to significantly influence the T cell responses, the effective recognition of the toxin-class II complex by the TCR may also contribute to such responses. PMID- 1940374 TI - Biochemical and functional analysis of extracellular stress proteins of Mesocestoides corti. AB - Previous studies of the serum antibody response in mice to Mesocestoides corti infection indicated that molecules released by the parasite influenced the production of IgM and IgG1 to the exclusion of other isotypes. Two proteins isolated from M. corti culture supernatants were found to be homologous to the 70 kDa heat shock proteins (hsp70) and Escherichia coli GroEL families of stress proteins. The proliferative responses of splenic lymphocytes from infected mice were assessed to unfractionated M. corti supernatants as well as the 70- and 60 kDa stress protein homologs isolated from supernatants. Lymphocytes from infected mice respond to complete supernatant and both of the isolated p70 and p60 stress protein homologs. In addition, supernatant from M. corti cultures stimulates an in vitro antibody response restricted to IgM and IgG1; the same isotypes induced during infection. These results suggest that stress proteins play an integral part in the immune response to M. corti and the associated isotype restriction. PMID- 1940375 TI - Influence of adjuvants on the antibody specificity to the Plasmodium falciparum major merozoite surface protein, gp195. AB - The effect of adjuvants on the specificity of immune responses to the Plasmodium falciparum gp195 protein was investigated using adjuvant formulations based on synthetic muramyl dipeptide and monophosphoryl lipid A derivatives, in parallel with CFA and alum. Although these immunomodulators were as effective as CFA in inducing an antibody response to gp195, there were distinct differences in the recognition of B cell epitopes by these antibody populations. We have also demonstrated that MHC control of antibody specificity can be related to the adjuvant used for immunization. In general, the potency of adjuvants, their ability to induce antibodies of a particular specificity, or their ability to overcome MHC control of immune responsiveness varied independently. These findings suggest a critical role of adjuvants in the determination of the specificity of the immune response to protein Ag. Thus, the influence of adjuvants should be a major consideration in studies on immunologic recognition, as well as in the design of modern subunit vaccines. PMID- 1940376 TI - Survival of human macrophages infected with Mycobacterium avium intracellulare correlates with increased production of tumor necrosis factor-alpha and IL-6. AB - The long term survival of peripheral blood derived human macrophages (M phi) from normal, healthy donors after infection with Mycobacterium avium intracellulare (MAI) correlates with the increased induction of TNF-alpha and IL-6 mRNA and protein by the infected M phi. This conclusion is based on the following observations: M phi from approximately 30% of the blood donors in our study die 3 to 4 days after inoculation (MAI-growth nonsupportive (NS], whereas M phi from the other donors survive inoculation with MAI for 7-10 days (MAI-growth supportive (S)). S-type M phi when infected with MAI had markedly increased amounts of TNF-alpha and IL-6 mRNA and protein when compared to NS-type M phi. The effect of LPS on the induction of TNF-alpha mRNA and protein was also significantly enhanced in S-type M phi in comparison to NS cells. In contrast, IL 1 beta mRNA and protein production had similar increases in both donor types when infected with MAI or stimulated with LPS. The phenotype of the donors in the amount of TNF-alpha and IL-6 produced in response to MAI infection remained stable for a period of more than 1 yr. Pretreatment of NS M phi with recombinant human granulocyte-macrophage-CSF, but not IFN-gamma, however, converted NS M phi into a S-type cell phenotype. These granulocyte-macrophage-CSF pretreated NS M phi survived infection with MAI for a longer period of time and also had increased production of both TNF-alpha and IL-6 mRNA and protein. Cultures of S type M phi infected with MAI had higher numbers of intracellular bacteria when compared to cultures of NS-infected M phi. Thus, increased survival of MAI infected human M phi in vitro is correlated to increased production of TNF-alpha and IL-6 in response to infection with MAI. PMID- 1940377 TI - Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. II. In vitro granuloma modulation induced by polyclonal idiotypic antibodies. AB - We have previously reported on Id/anti-Id-receptor interactions in clinical human schistosomiasis. These findings support a hypothesis that anti-SEA cross-reactive Id develop in some patients during the course of a chronic infection and participate in regulation of anti-SEA cellular immune responses. We report here on experiments that extend those observations to the regulation of granulomatous hypersensitivity measured by an in vitro granuloma model. T cells from chronic intestinal schistosomiasis patients were stimulated in vitro with anti-SEA Id and assayed in an autologous in vitro granuloma assay for modulation of granuloma formation. These anti-SEA Id-reactive T cells were capable of regulating autologous in vitro granuloma formation. Both CD4 and CD8 T cells could be activated to regulate granuloma formation. This regulatory activity, initiated with stimulatory anti-SEA idiotypic antibodies, was antigenically specific and was dependent on the presence of intact F(ab')2 Ig molecules. The ability to elicit this regulatory activity appears to be dose dependent and is more easily demonstrated in chronically infected intestinal patients or SEA-sensitized individuals. These data support the hypothesis that anti-SEA cross-reactive Id are important in regulating granulomatous hypersensitivity in chronic intestinal schistosomiasis patients and these cross-reactive Id appear to play a major role in cell-cell interactions that result in the regulation of anti-SEA cellular immune responses. PMID- 1940378 TI - Murine CD8+ cytotoxic T lymphocytes lyse Toxoplasma gondii-infected cells. AB - Studies were performed to determine whether CTL against Toxoplasma gondii infected cells could be induced in a murine model of T. gondii infection in which CD8+ T lymphocytes have been shown to play a major role in resistance against this parasite. In 51Cr release assays, nylon wool nonadherent spleen cells from BALB/c (H-2d) mice immunized with the temperature-sensitive (ts-4) mutant strain of T. gondii were cytotoxic for T. gondii-infected P815 (H-2d) mastocytoma cells but not for uninfected cells. This cytotoxic activity was remarkably increased after in vitro stimulation with T. gondii-infected syngeneic spleen cells. The effector cells were shown to be CD8+ T lymphocytes, because the cytotoxicity was significantly inhibited by depletion of CD8+ T lymphocytes but not by depletion of CD4+ T lymphocytes. This cytotoxic activity was genetically restricted. Spleen cells from T. gondii-immune BALB/c mice were not cytotoxic for T. gondii-infected EL4 (H-2b) thymoma cells, whereas spleen cells from T. gondii-immune C57B1/6 (H 2b) mice were cytotoxic for T. gondii-infected EL4 cells but not for T. gondii infected P815 cells. The cytolytic activity of CD8+ T lymphocytes against T. gondii-infected cells might be a mechanism whereby these cells confer resistance against T. gondii. PMID- 1940379 TI - Regulation of HILDA/LIF gene expression in activated human monocytic cells. AB - We have previously shown that human monocytes express HILDA/LIF gene and its protein product upon stimulation. In the present study we have investigated some of the possible mechanisms involved in the regulation of HILDA/LIF gene expression in activated human monocytes and compared them to those of granulocyte colony-stimulating factor (G-CSF) and IL-1 beta gene expression. In the absence of added stimuli HILDA/LIF mRNA was barely detectable in isolated monocytes. HILDA/LIF mRNA accumulation was weakly induced by stimuli such as LPS or phorbol ester. However, a synergy was observed when each stimulus was used in combination with 1,25-dihydroxyvitamin D3. Nuclear run-on analysis did not detect an increase in HILDA/LIF gene transcription upon stimulation with LPS or phorbol ester in combination with 1,25-dihydroxyvitamin D3. HILDA/LIF mRNA half-life showed an increase when phorbol ester and 1,25-dihydroxyvitamin D3 were used in combination over that obtained for each stimuli alone. HILDA/LIF mRNA expression was largely inhibited when monocytes were stimulated in the presence of cycloheximide (CHX) added either at the onset or 4 h after the beginning of the stimulation period. When CHX was added at later time points, 2 h before cell harvesting, HILDA/LIF mRNA levels were superinduced when compared with those in cells stimulated in the absence of CHX. This superinduction can be at least partially explained by post transcriptional mechanisms, since HILDA/LIF mRNA half-life in CHX-superinduced cells was significantly increased when compared with values on stimulated CHX untreated cells. In contrast to HILDA/LIF, G-CSF and IL-1 beta mRNA accumulation showed a different response pattern to the same stimuli, and a augmentation of their gene transcription was detected by the run-on technique in activated monocytic cells when compared with controls. Furthermore, G-CSF and Il-1 beta mRNA levels were superinduced in monocytes stimulated in the presence of CHX from the onset of the stimulation period. These studies indicate that, when compared to G-CSF and IL-1 beta, the expression of HILDA/LIF gene is under the control of relatively specific regulatory mechanisms. HILDA/LIF gene expression is controlled by newly synthesized proteins acting at early and late time points of the stimulation period and with opposite effects on HILDA/LIF mRNA levels. Finally, HILDA/LIF mRNA levels are regulated by post-transcriptional mechanisms of mRNA stabilization probably controlled through labile newly synthesized proteins. PMID- 1940380 TI - Expression of protein kinase C genes in hemopoietic cells is cell-type- and B cell-differentiation stage specific. AB - We have studied the expression of mRNA encoding all known protein kinase C (PKC) isozymes (alpha, beta, gamma, delta, epsilon, zeta, and eta) in murine tumor cell lines that exemplify hemopoietic cells arrested at different stages of development as well as in normal hemopoietic cells. We demonstrate that some of the isozymes, PKC-alpha, -beta, and -eta, are differentially expressed in different lineages. PKC-alpha and -beta generally are not detectable in myeloid cell lines, where PKC-delta is the predominant isoform. Both PKC-alpha and -beta are abundant in most T and B lymphocytic lines, but steady state levels of PKC beta mRNA are lowest in plasma cell tumors, which exemplify the terminally differentiated B lymphocyte. In contrast, the levels of PKC-alpha mRNA remain high in plasma cell tumors, and a novel, 2.5-kb PKC-alpha mRNA gains prominence. PKC-eta mRNA is the major PKC isoform expressed in T lymphocytes, but it also is highly abundant in some myeloid lines. PKC-delta is expressed at high levels in all the lines we studied, whereas PKC-epsilon and -zeta are found in most cells but only at rather low levels. Analysis of myeloid clones derived from bipotential B lineage progenitor cell lines suggests that the B cell phenotype is associated with the expression of PKC-alpha. The close correlation of protein levels with mRNA levels indicates that PKC expression in hemopoietic cells is mainly regulated at the level of mRNA. The lineage- and differentiation stage specific patterns of PKC-isozyme expression presented here suggest the involvement of specific PKC isozymes in differentiation as well as lineage determination of hemopoietic cells. PMID- 1940381 TI - Gene expression of the A- and B-chain of mouse C1q in different tissues and the characterization of the recombinant A-chain. AB - Immunoscreening of a mouse macrophage cDNA library with an anti-mouse C1q antibody resulted in the isolation of cDNA clones. The deduced amino acid sequence was homologous to the A-chain of human C1q. Homology on the DNA level was found to be 76% and on the protein level 72% thus it appeared the clones coded for the mouse C1q A-chain. An immunoblot of murine serum C1q separated by SDS-PAGE was detected with an A-chain specific antibody that had been affinity purified on recombinant mouse C1q A-chain expressed in Escherichia coli. The antibody preparation reacted exclusively with the mouse C-chain (as defined by SDS-PAGE). Northern blot analysis with strand-specific cDNA probes coding for the A- and B-chain of murine C1q showed that mouse peritoneal macrophages produced the highest concentration of C1q gene transcripts. RNA from mouse spleen, thymus, heart, and brain gave substantial hybridization signals, whereas RNA preparations from liver, kidney, lung, and small intestine appeared to contain only trace amounts of C1q mRNA. In a Northern blot analysis of different guinea pig cells and tissues, only RNA preparations from peritoneal macrophages hybridized with the mouse C1q probes. These results indicate that macrophages are a major site of C1q biosynthesis. PMID- 1940382 TI - Clonal characterization of the human IgG antibody repertoire to Haemophilus influenzae type b polysaccharide. IV. The less frequently expressed VL are heterogeneous. AB - We previously demonstrated that the human anti-Haemophilus influenzae type b polysaccharide (Hib-PS) VL repertoire is dominated by a product of the V kappa II gene, A2, and that V kappa II-A2 anti-Hib-PS antibodies have little or no somatic mutation in VL. To further study this VL repertoire, we studied non-A2 anti-Hib PS antibodies that were identified either serologically or by amino-terminal amino acid sequence analysis. Of 15 non-A2 anti-Hib-PS antibodies from 12 vaccinated adults, we found four V lambda, five V kappa I, one non-A2 V kappa II, four V kappa III, and one V kappa IV antibodies. As expected, all but two of these subjects also produced V kappa II-A2 antibodies. Interestingly, one of these subjects lacks the A2 gene in the germ line. However, both subjects who did not produce detectable V kappa II antibody did produce normal amounts of total anti-Hib-PS antibody after vaccination. Candidate V kappa genes for the non-A2 antibodies were identified by comparison of up to 60 VL amino acid residues, including CDR1 and CDR2, with all sequenced V kappa genes. V kappa I antibodies appear to be products of three newly sequenced V kappa I genes, O8, O18, and L11, that are reported here. The O8 and O18 genes encode identical amino acid sequences. The non-A2 V kappa II antibody is a likely product of the A1 or A17 genes, the V kappa III antibodies are likely products of the A27 gene, and the V kappa IV antibody is a product of the single V kappa IV gene, B3. Unlike V kappa II-A2 antibodies, the V kappa I, V kappa III, and V kappa IV antibodies differed by one to five CDR residues from the germ line product of the candidate genes, suggesting the presence of somatic mutations. Thus, anti-Hib-PS antibodies can be divided into two types, the most frequently observed A2 antibodies with little or no somatic mutation and non-A2 antibodies that likely contain somatic mutations. PMID- 1940383 TI - VDJ genes in VHa2 allotype-suppressed rabbits. Limited germline VH gene usage and accumulation of somatic mutations in D regions. AB - In this study we investigate the molecular genetic basis for VHa- Ig. Knowing that the expression of VHa allotype Ig is suppressed by neonatal injection of rabbits with anti-VHa allotype antibody, and that the decreased level of VHa allotype Ig, VHa+, in the suppressed rabbits is compensated for by an increase in VHa- Ig, we determined the nucleotide sequences of 41 VDJ genes from a2/a2 rabbits neonatally suppressed for the expression of a2 Ig. We compared these nucleotide sequences to each other and identified two groups of VH sequences. We predict that the molecules of each group are encoded by one germline VH gene. Inasmuch as VHa+ Ig is encoded predominantly by one germline VH gene, VH1, it appears that more than 95% of the VDJ repertoire of rabbits may be encoded by as few as three germline VH genes. A genomic VDJ gene whose VH sequence was similar to those of group I molecules was expressed in vitro and was shown by ELISA to encode molecules of the VHa- allotype, y33. Analysis of the D regions in the VDJ gene indicated that germline D2b and D3 gene segments were preferentially used in the VDJ gene rearrangement. A comparison of sequences of D regions of the 41 VDJ gene rearrangements in 3-, 6-, and 9-wk-old rabbits to sequences of germline D gene segments showed an accumulation of mutations in the D region. Inasmuch as we have previously shown that V regions of rabbit VDJ genes are diversified, in part, by somatic gene conversion, it appears now that rabbit VDJ genes diversify by a combination of somatic mutation and somatic gene conversion. PMID- 1940385 TI - Thiophilic adsorbents for RIA and ELISA procedures. AB - Three types of agarose derivatives have been prepared and investigated as adsorbents for radioimmunoassay and ELISA analysis. The analytical systems were evaluated using beta 2 microglobulin as a model. After a competitive reaction between the immunocomponents in solution, the formed immune complexes were adsorbed onto the adsorbent in the presence of 0.5 M potassium sulfate in 0.1 M Tris, pH 7.5. The binding constant between the interaction site on human IgG and the adsorbent 3-(2-pyridylthio)-2-hydroxypropylagarose (Py-S-gel) was determined to be 1.5 x 10(7) M-1 and the binding capacity was 20 mg/ml gel. The immune complex was desorbed by deleting potassium sulfate from the buffer, and only 0.5% of the total applied protein remained after washing the adsorbent with 0.5 M NaOH. The same adsorbent can be used repetitively with different systems. PMID- 1940384 TI - Treatment of mice bearing BCL1 lymphoma with bispecific antibodies. AB - Bispecific antibodies with specificity for the CD3/TCR complex of CTL and a target cell Ag can bridge both cell types and trigger cellular cytoxicity. We have produced bispecific antibodies, directed against the surface-expressed Id of the mouse BCL1 lymphoma and the mouse CD3 complex, by hybrid-hybridoma fusion. Two recombination Ig were purified to homogeneity: B1 X 7D6F, which is univalent for Id and CD3 binding and B1 X 7D6M, which is univalent for Id binding but has lost the CD3 binding because of association of the anti-CD3 H chain with the inappropriate L chain. In vitro studies indicate that bridging the TCR/CD3 complex of resting T cells with tumor IgM Id and the appropriate bispecific antibody induced proliferation and secretion of IL-2. Furthermore, in cytotoxicity assays using 51Cr-labeled tumor cells, preactivated T cells could be targeted with the bispecific antibody to give complete lysis of the Ag+ tumor. Finally, the activity of the bispecific antibody was confirmed in vivo. Animals treated i.v. with 5 micrograms of bispecific antibody 9 days after receiving BCL1 cells were cured. Furthermore, when these animals were checked at 150 days for dormant or variant tumors, as have been reported after other forms of immunotherapy in this model, none could be found. Immunotherapy experiments comparing a mixture of control antibodies with the bispecific antibody demonstrate that tumor cell-T cell bridging is established in vivo and is required for therapeutic success. These results indicate the importance of bispecific antibodies as a novel form of treatment for cancer. PMID- 1940386 TI - Prevention of nonspecific binding of immunoglobulin to Staphylococcus aureus protein A in ELISA assays. AB - The Fc region of IgG of most mammals binds protein A on S. aureus resulting in high backgrounds when measuring specific antibodies to S. aureus in the ELISA. Removal of protein A from S. aureus or modification of the Ig Fc to prevent binding to protein A could affect specific antibody binding. We compared effects of blockage of Fc binding to protein A with purified protein A to trypsin removal of protein A from S. aureus, on specific antibody binding. When NMS was incubated without and with protein A (0 microgram, 50 micrograms, 200 micrograms and 400 micrograms) and high protein A Cowan I was the bound S. aureus antigen in the ELISA, absorbance OD405 was 0.769, 0.240, 0.224 and 0.210 +/- SE 0.026. When mouse Mab (IgG1, kappa) to bovine IgA was incubated without and with protein A (400 micrograms) prior to reaction with bovine IgA in the ELISA, absorbance was 0.645 and 0.639, indicating protein A had no effect on specific antibody binding. To determine the effect of trypsin on specific binding, Becker S. aureus was trypsin treated before linking it to microtiter wells. When Mab (IgM) to Becker (Nelles et al., Infect. Immun. (1985) 49, 14) was incubated with protein A (400 micrograms) before use in the ELISA, trypsin treatment of Becker resulted in reduced specific antibody activity (untreated Becker = 1.306, trypsin treated Becker = 0.331). These results suggest that purified protein A can be used to block nonspecific binding via Fc of Ig to S. aureus, thus avoiding trypsin denaturation of surface antigens. PMID- 1940387 TI - Quantitation of solid-phase immunoassays using a fibre-optic reflectance spectrophotometer. AB - A reflectance measuring instrument (fibre-optic spectrometer linked to a personal computer) which will quantitate the results of immunoassays that result in the deposition of a coloured chromophore on a membrane or other similar solid phase (SP) is described and the reflectance spectra of some chromophores which are commonly produced or used in SP immunoassays are presented. The instrument has been used in conjunction with silver-enhanced SP-immunogold capture assays to determine the concentrations in serum of IgG and of IgM rheumatoid factor (RF) and the results have been compared with those obtained by rate nephelometry and latex agglutination assays, respectively. It is concluded that fibre-optic reflectance photometry is an accurate and useful means of quantitating SP immunoassays in which coloured chromophores are produced and that the results obtained from such immunoassays are comparable to those given by established procedures. PMID- 1940388 TI - Antigen detection in invasive aspergillosis. AB - The application of a reverse passive latex agglutination test and dot-blot assay are reported in the diagnosis of 50 proven cases of invasive aspergillosis and 28 suspected cases. At a latex titre cut off of greater than or equal to 1 in 8 the test had a sensitivity of 29.4%, specificity of 96.3% and efficiency of 41.4%. This was in sera taken when the diagnosis was first suggested. The sensitivity rose to 55.1% when sera with the maximum level of antigen were examined. The dot blot was more sensitive with 33.3% of cases being positive in the initial sera. This increased to 61.5% when the serum with the maximum antigen level was taken. PMID- 1940389 TI - Production of monoclonal antibodies against inactivated alpha 1-antitrypsin. Cross-reactivity with complexed alpha 1-antitrypsin and application in an assay to determine inactivated and complexed alpha 1-antitrypsin in biological fluids. AB - 15 different monoclonal antibodies (mcAbs) have been raised against the cleaved (inactive) form of the serpin alpha 1-antitrypsin (AT). In initial experiments these mcAbs were analysed for their ability to bind the native and the cleaved form of this inhibitor: eight of the 15 mcAbs appeared to react predominantly with cleaved AT. Additional experiments with mixtures of purified native AT, AT complexed to neutrophilic elastase and inactivated AT revealed that all mAbs that preferentially reacted with inactivated AT also bound to complexed AT. Using two of the mcAbs against inactivated AT a quantitative and sensitive sandwich-type radioimmunoassay was developed to determine levels of proteolytically inactivated AT in biological fluids. With this assay increased levels of inactivated AT were found in synovial fluid from patients with rheumatoid arthritis corresponding to about 2.4% (range 0.3-11%) of total AT. Approximately 10% of this inactivated AT appeared to consist of AT complexed to neutrophil elastase. The mcAbs described here further illustrate the structural resemblance between the complexed and cleaved forms of AT. In addition, these mcAbs appear to be useful tools for the study of AT in human disease. PMID- 1940390 TI - Long term cultures of human monocytes in vitro. Impact of GM-CSF on survival and differentiation. AB - In vitro differentiation of human monocytes (Mo) provides large amounts of mature and functionally competent macrophages (M phi) which may be used as potentially powerful anticancer agents for adoptive immunotherapy. Granulocyte macrophage colony stimulating factor (GM-CSF) was evaluated for its ability to influence long term cultures of Mo-derived M phi. Large quantities of Mo isolated by leukapheresis and elutriation were cultured in non-adherent cell culture bags or in plastic flasks with or without GM-CSF. At various stages of differentiation, GM-CSF treated M phi were recovered and assayed for survival, morphology, surface antigens, functional properties and proliferation in comparison with control M phi. In the present paper, we demonstrate that GM-CSF at a concentration of 50 U/ml (5 ng/ml) promotes better cell survival and the differentiation of Mo into M phi displaying certain morphological differences as compared to control M phi such as an increased expression of Max-1 antigen, CR3 and Fc gamma II receptors, higher phagocytic properties and increased capacities of cytotoxicity and TNF secretion when the cells are further activated by IFN-gamma. Furthermore, GM-CSF treated cells exhibit a low-grade proliferation although the nature of the proliferating cells has not been entirely elucidated. We conclude that the GM-CSF treated M phi would be particularly suitable for adoptive immunotherapy. PMID- 1940391 TI - Measurement of anti-phospholipid antibodies by ELISA using beta 2-glycoprotein I as an antigen. AB - The requirement of plasma cofactor beta 2-glycoprotein I for binding autoantibodies against anionic phospholipids has been reported. We describe the development of an enzyme-linked immunosorbent assay (ELISA) for anti-phospholipid antibodies using highly purified beta 2-glycoprotein I for coating microtitre plates. Intra- and interassay coefficients of variation, determined with serum pools of low, medium and high positivity, ranged between 3% and 18%. 54 sera from patients with systemic lupus erythematosus and related autoimmune disorders were analyzed by this assay; the results correlated well to those obtained in an ELISA using anionic phospholipids on the solid phase (r = 0.85, P less than 0.001). The two ELISA systems showed similar sensitivities although 8/31 positive sera scored negative in the beta 2-glycoprotein I ELISA. The latter group of eight sera showed significantly higher anti-phosphatidylcholine/anti-phosphatidylserine binding ratios than the group of 23 sera which scored positive in both assays. This new assay should permit accurate measurement of most of the clinically relevant anti-phospholipid antibodies and avoid inconsistencies likely to arise from secondary interactions that characterize lipid-based ELISA. PMID- 1940392 TI - Preparation of clinical grade proteins produced by recombinant DNA technologies. AB - Methods were developed for the production of clinical grade malaria vaccine candidates expressed in E. coli by recombinant DNA technologies. The essential features of the purification protocol consist of (1) mechanical breakage of host cells and solubilization of the recombinant proteins in 6 M guanidine hydrochloride; (2) ammonium sulfate fractionation; (3) affinity chromatography on a Ni(2+)-chelate gel in the presence of 6 M guanidine hydrochloride; and (4) ion exchange chromatograph on a Phospho Ultrogel column in the presence of 6 M urea. The use of undesirable chemicals (PMSF, DFP, TFA, acetonitrile, etc.) was avoided rather than demonstrating their complete removal after the purification steps. Testing of chromatographic fractions for host-cell proteins and the elimination of fractions with E. coli protein content was found necessary to obtain a final product that contained less than 0.01% of host derived proteins. The recombinant proteins were renatured either from 8 M urea or from 6 M guanidine hydrochloride by increasing the pH to 10.5 in the presence of glycine and EDTA, reduction with DTT, dilution to a protein concentration below 1 mg.ml-1, and dialysis against 0.9% NaCl. The method presented here can be tailor-fit, with minor modification, for the purification of almost any recombinant protein and the final product satisfies current regulations concerning the production of clinically acceptable therapeutic products. PMID- 1940393 TI - A specific and reliable bioassay for the detection of femtomolar levels of human and murine tumor necrosis factors. AB - A reliable, highly sensitive, cytolytic bioassay for the quantitation of both human and murine tumor necrosis factor (TNF) is described. The assay is 2-180 fold more sensitive than other currently described bio- or immunoassays (limits of detection: 500 fg/ml (29 fmol/l) human TNF-alpha, 200 fg/ml (12 fmol/l) murine TNF-alpha and 130 fg/ml (7 fmol/l) human TNF-beta). The assay, which uses L929-8, a newly isolated subclone of the murine fibroblastoid cell line L929, detects human TNF-alpha approximately 180-fold more sensitively than previously described L929 subclone assays. Maximum sensitivity is obtained by preincubating L929-8 cells at 37 degrees C with 2 micrograms/ml actinomycin D (1-2 h), then culturing with TNF at 40 degrees C for 20 h in medium containing high serum (15% FBS). Relative viable cell content in 96-well microtiter plates is determined colorimetrically by uptake of the non-carcinogenic dye neutral red. Other cytokines have no effect, either alone or in combination with TNF. Cytokines tested were IL-1 through IL-6, GM-CSF, G-CSF, CSF-1, LIF, TGF-beta, NGF, Epo or IFN-gamma, LPS, PGE2, dexamethasone and cyclosporin A, also have no effect, either alone or in combination with TNF. L929-8 cells maintain the above sensitivity to TNF for at least 4 months in continuous culture. Thus, the assay allows rapid, inexpensive, reliable and specific quantitation of rodent and human TNFs. Its very high sensitivity should allow accurate detection of biologically active TNF in biological fluids such as human serum. PMID- 1940394 TI - Paratesticular fibrosarcoma. PMID- 1940395 TI - Some observations on neuro-enteric cysts. PMID- 1940396 TI - Injury and the spleen: to remove it or not to remove it. PMID- 1940397 TI - Rheumatoid arthritis. PMID- 1940398 TI - World Health Day. PMID- 1940399 TI - Aims of the IMA and medical universities potential. PMID- 1940401 TI - Reversal of nostril dominance by posture. AB - Reflex reversal of differential air flow through nostrils (DAFTN) by the adoption of suitable lateral recumbent position was studied in male Nigerian subjects. The subjects who demonstrated more air flow through the left nostril initially in the supine position, adopted left lateral recumbent (LLR) position which brought the decongested left nostril to the down-side and the congested right nostril to the upside. Within 3 to 4 minutes after the adoption of LLR position, the air flow through the nostrils was equalised and by 11th minute the DAFTN was reversed, with more air flowing through the upsided right nostril. Return of the subjects to supine position could not result in the recovery to the initial pattern of DAFTN. It is suggested that reversal of DAFTN with adoption of suitable lateral recumbent position was a reflex effect due to the pressure stimuli to the lower lateral side of the body particularly around the shoulder region and effect was mediated through the sympathetic innervation to mucosal venous sinuses of the nostrils. Possibility of gravitational effect was ruled out. PMID- 1940400 TI - Radioiodine therapy in thyrotoxicosis. AB - One hundred and two patients (81 females, 21 males) suffering from thyrotoxicosis as diagnosed clinically and confirmed by laboratory investigations including the estimation of thyroid hormones in blood were treated with radioiodine (I-131) at the University of Minnesota Hospital between 1976 and 1986. Nine (9%) patients needed two and 3 (3%) patients needed three therapeutic doses of I-131. The age range of the patients was 17-82 years (mean 43, SD 17). The doses of I-131 administered ranged from 3.9 to 100 mCi (mean 13.7). Twenty of these patients received a relatively high dose from 20 to 100 mCi. The others were given smaller calculated doses based on radioiodine uptake and thyroid size is determined by palpation and nuclear scans. Of the 73 patients for whom follow-up information was available, 66 (90%) eventually became hypothyroid as judged by clinical criteria. These data also suggest that the incidence of hypothyroidism is quite independent of the dose (microCi/g thyroid) administered. PMID- 1940402 TI - Transferrin saturation studies in male adults showing high prevalence of iron deficiency. AB - Estimation of serum iron, total iron binding capacity (TIBC) and transferrin saturation was performed in 62 apparently healthy male medical students. All had haemoglobin over 140 g/1. Low serum iron, elevated level of TIBC and transferrin saturation under 20% indicating iron deficiency state was found in 2 subjects. Elevated values of TIBC was found in 25 (40.32%) students as evidence of latent iron deficiency. Such high prevalence of iron deficiency in an affluent group indicates widespread iron deficiency in the general population. PMID- 1940403 TI - Incidence of neonatal bacterial infection in cases of prolonged rupture of amniotic membrane. AB - Thirty cases of premature rupture of amniotic membrane were studied bacteriologically. Twenty cases showed growth of organisms from one or more sites at birth. From 20 control cases no pathogenic organism could be isolated. Out of these 20 cases showing growth of organisms 8 neonates developed clinical infection (deep and superficial) subsequently. The organisms grown from vaginal swab and umbilical swab culture showed maximum correlation to the organism from the infected neonates. Esch coli was found to be most common organism causing infections, next to it was Staph aureus. Growth of anaerobic organisms was found only in cases of prolonged rupture of membrane in mother, but not isolated from infected babies. So bacteriological studies of vaginal, placental, umbilical and nasal swabs and cord blood just after the birth of baby may be of some help in predicting the onset of neonatal infection. PMID- 1940404 TI - Ultrasound in choledocholithiasis. AB - Twenty-five patients of obstructive jaundice due to choledocholithiasis, were prospectively evaluated by ultrasonography and cholangiography. Ultrasound could demonstrate choledocholithiasis in 10 patients (40%). Choledocholithiasis in non dilated ducts could be demonstrated only in one patient. All cases were diagnosed by cholangiography. Ultrasound, though an accepted modality of choice for diagnosing cholelithiasis, has a limited role in the diagnosis of choledocholithiasis. Ultrasonography (USG) is the screening modality of choice to distinguish obstructive from non-obstructive jaundice. It is highly accurate in the diagnosis of cholelithiasis but its role in detection of choledocholithiasis is less clear. Choledocholithiasis complicates 10% of all cases of cholecystitis and occurs in 2-4% of postcholecystectomy patients. The present study deals with the diagnostic value of USG in cases of choledocholithiasis subjected to USG prior to cholangiography and surgery. PMID- 1940405 TI - Perinatal mortality rate in a south Indian population. AB - Perinatal mortality rate was assessed for 13964 consecutive births in SAT Hospital, Trivandrum, South India, during a period of one year. The overall perinatal mortality rate was 42.75, stillbirth rate 24.41 and early neonatal mortality rate 18.79. The perinatal mortality rate in multiple pregnancy was 156.65. Preventable causes of perinatal mortality still make a major contribution to perinatal deaths in developing countries. PMID- 1940406 TI - Hazards of smoking. AB - A strong association exists between cigarette smoking and several diseases namely, cancer of the lung, bronchitis and emphysema, cancer of the larynx, oral cavity and oesophagus, gastric and duodenal ulcers, Crohn's disease, cancer of the bladder, coronary artery disease, macrocytosis, polycythaemia, leukaemia, etc. This is due to the harmful constituents of cigarette and other modalities smoking. Smokers not only harm themselves but also harm those around. Foetal malformations, abortions, stillbirths, prematurity and low birth weight are common in smoker mothers. These are the effects of passive smoking. There is no safer cigarette in the market even by lowering its harmful constituents. Mass education about the hazards of smoking with emphasis on complete stoppage of smoking is the only way to prevent its rising incidence. PMID- 1940407 TI - Congenital malformations--time to act. PMID- 1940408 TI - Reproductive rights of women and AIDS. PMID- 1940410 TI - Prevalence of hepatitis B virus (HBV) markers and human immunodeficiency virus (HIV) in employees of a blood transfusion centre. AB - Blood bank staff, 8 out of 25 (32%) have been exposed to hepatitis B virus (HBV) and the prevalence of HBV markers in blood bank employees handling high risk subjects show hepatitis B surface antigen (n = 1), hepatitis B surface antibody (n = 7), hepatitis B core antibody (n = 6) and combined hepatitis B surface antibody and hepatitis B core antibody (n = 6) seropositivity but all are negative to human immunodeficiency virus (HIV). Serum alanine aminotransferase was raised in the employees than normal subjects and it is suggestive of sub clinical hepatitis. The employees of blood bank should be trained for proper handling of test materials and must be periodically monitored for HBV and HIV. Immunisation for HBV is mandatory only for the employees of transfusion centre which handles high risk subjects. PMID- 1940409 TI - Opinion survey of physicians on ethical issues in medical research. AB - A total of 3622 physicians registered in the Association of Physicians of India were contacted through mail and requested to respond to a semistructured questionnaire pertaining to different aspects of medical ethics, with particular focus on informed consent. Six hundred twenty-nine physicians (17.4%) responded to the questionnaire; 86% of the respondents reported having had no formal training in medical ethics; 49% of the subjects who undertook research obtained oral consent only. Majority of the respondents noted the relevance of ethics in different medical situations, though in certain areas like community health and research using animals ethical issues were felt to be less important. Patients' inability to come for regular follow-up and illiteracy were opined to be the main constraints in obtaining consent. Opinion on the amount of information to be imported to research participants as part of informed consent was at variance with standard guidelines. Physicians who reported having had an orientation course in medical ethics and those with prior research experience were more aware of ethical issues. Majority of the professionals desired for inclusion of ethics in medical curriculum. PMID- 1940411 TI - Fine needle aspiration cytology, imprint cytology and tru-cut needle biopsy in breast lumps: a comparative evaluation. AB - Fine needle aspiration cytology, imprint cytology and tru-cut needle biopsy were performed in 86 patients with breast lump and the results of these techniques were finally compared with the incisional or excisional biopsy in all the patients. Fine needle aspiration cytology had the sensitivity of 96.8% and specificity of 100%, the imprint cytology had the sensitivity of 98.4% and specificity of 100%. While the tru-cut needle biopsy had the sensitivity and specificity of 100% though in this technique 15 of 86 (17.4%) specimens were rejected as insufficient for any diagnosis. PMID- 1940412 TI - Malabsorption in thyroid dysfunctions. AB - Studies of intestinal absorptive functions in 11 hyperthyroid and 14 hypothyroid patients showed that steatorrhoea was common in hyperthyroid patients and rare in hypothyroid patients. D-xylose malabsorption was present in both the groups of thyroid disorders being more common in hypothyroid one. Occasionally vitamin B12 malabsorption was found in 2 hypothyroid patients. Jejunal mucosal changes were almost unremarkable. Both fat and carbohydrate malabsorption in both groups of patients appeared to be casually related to the thyroid dysfunction. PMID- 1940414 TI - Protrusion of upper lumbar intervertebral discs (long term follow-up of operated cases). AB - Fifteen operated cases of upper lumbar disc prolapse have been reviewed. They were categorised under 4 types of clinical presentation. There was no clear correlation between the level of the prolapse, clinical presentation, and type of disc prolapse as observed at surgery. On long term follow-up 11 of the 15 (73%) cases had an excellent result and were leading a normal life. The result is poor in patients with severe paraplegia. PMID- 1940413 TI - Outcome of teenage pregnancy and labour: a retrospective study. AB - During the period of study of 3 years (1985-1987), 4698 (18.68%) cases of labour in teenage mothers were recorded out of a total of 25,142 deliveries in the obstetric unit. Preponderance of primigravida (76.6%) and cases from rural areas (51.3%) were recorded. Antenatal care was nil or inadequate in 48.6% cases. Eclampsia and pre-eclampsia affected teenage mothers (10.6%) were much more frequent than mothers of 20 years of age and above (5.2%). Incidence of 30% low birth weight baby, 20.1% prematurity and 16.4% perinatal mortality were recorded. PMID- 1940415 TI - Non-sporing anaerobes in hospital sepsis. AB - In comparison to normal controls, the non-sporing anaerobes were often isolated from orodental sepsis (42% to 44.4%), chronic suppurative otitis media (40%), septic abortion (40.3%), uterocervical wound (45.4%), vaginitis (50%) and cancer cervix (50%). This was true (40%) in perforating ulcers of foot in leprosy. These organisms were less frequently noted in abdominal (11%) and episiotomy (22.8%) wounds and leucorrhoea (33.3%). The role of non-sporing anaerobes was also suggested by the high percentage ratio of number of isolates to number of cases and by its primary isolation in moderate to heavy number. Barring the cases of cancer cervix, the aerobic bacteria were the most common (78.8% to 100%) in all other conditions. PMID- 1940417 TI - Labial agglutination. PMID- 1940416 TI - Study of ascitic fluid in relation to systemic and portal venous blood in hepatic cirrhosis. AB - Twenty uncomplicated cases of cirrhosis of liver, proved by liver biopsy, and free from other systemic diseases were studied. Glucose (pre- and postprandial) and electrolytes (Na+, K+, Cl-) values were compared to those of systemic and portal venous blood. Chloride level in ascitic fluid was found to be significantly high in cirrhosis, as compared to portal and systemic venous blood. Sodium and glucose levels were similar in ascitic fluid and portal venous blood except in two cases complicated with tuberculous peritonitis, where pre- and postprandial glucose levels were considerably low. In 55% cases, there was impaired glucose tolerance, as measured by pre- and postprandial glucose levels in systemic venous blood. PMID- 1940418 TI - Barotrauma: an unusual cause of bilateral tension pneumothorax. PMID- 1940420 TI - Paroxysmal nocturnal haemoglobinuria and hepatic venous thrombosis: an update. PMID- 1940419 TI - Tuberculous brain abscess. PMID- 1940421 TI - Consumer Protection Act and doctors. PMID- 1940422 TI - Current status of treatment in rheumatic disorders (the newer generation of non steroidal anti-inflammatory drugs). PMID- 1940423 TI - [Future of hospitals]. PMID- 1940424 TI - [Burch's procedure. Value of association with fixation to the promontorium and colpoperineorrhaphy]. AB - One hundred and ninety nine patients complaining of genuine stress incontinence not previously treated underwent Burch colposuspension. The operation has been either isolated (42.2%) or associated to a vaginal repair (36.2%) or associated to a vaginal repair and a sacral hysteropexy (21.6%). No serious operative complication occurred. The overall rate of postoperative complications was of 14% without significant difference between the surgical procedures. The overall clinical cure rate for stress incontinence was 90%. The rate of failure was significantly higher when the Burch operation was performed alone. The failures were revealed mostly in the six first months, confirming the stability of the results (20 months average follow-up). The present data confirms that Burch colposuspension is effective in stress urinary incontinence. The authors recommend a systematic association to a vaginal repair and, in case of bladder descent, to a sacral hysteropexy. PMID- 1940425 TI - [Treatment of calculi to the terminal ureter by extracorporeal piezoelectric lithotripsy. First experiment in Grenoble]. AB - Piezo-electric shock wave lithotripsy was successfully performed in 20 patients out of 25 presenting with distal ureteral stones. Echographic adjustment of the stone remains the very most important point of the technique. The treatment is non invasive, doesn't require any in-hospital stay and displays good tolerance. PMID- 1940426 TI - [Lithotripsy for pelvic lithiasis with the Dornier system with radiological location]. AB - The authors report their results with 58 patients presenting with pelvic lithiasis who were treated by extracorporeal lithotrity with the Dornier HM3 system. They describe the appropriate procedure of analgesia and emphasize the difficulties to locate the pelvic calculi, which sometimes requires resorting to urography during the treatment. Out of the 58 cases, success was total in 55 (94.83%), after one session of lithotrity in 52 of them and after two sessions in 3. In 2 of the 3 cases of failure, the calculi were monohydrated calcium oxalate stones located very high in the ischiadic incisure. Five cases of presacral lithiasis were treated in the ventral position, successfully in 3 cases and without success in 2. Thus it appears that shock wave lithotrity with the Dornier HM3 system with radiological location is highly effective for the treatment of pelvic lithiasis. PMID- 1940427 TI - [Is dysuria an objective or subjective concept?]. AB - A prospective study was carried out in 100 consecutive male patients coming to consultation in the department. These men, whose average age was 65 years (32 82), and who had come for various reasons, answered a questionnaire on the quality of their urine flow, which was rated on a scale ranging from 1 to 4. The results of flow rate measurements were classified in 4 categories according to the maximum flow rate and to the volume of micturation, which always was greater than 150 ml. The comparison of the subjective appreciation and of the objective value showed frequent discrepancies (over- or under-evaluation). These results were analysed according to various parameters, and in particular to the patients' age. It thus appears that one third of the patients only have an accurate appreciation of the quality of their micturation. PMID- 1940428 TI - [Relative phimosis on erection. Conservative plastic procedure with an asymmetrical Z plasty]. PMID- 1940429 TI - [Tumor of the urinary tract discovered after renal trauma. Medico-legal implications of a case]. AB - A case of a tumor of the urinary tract discovered after renal trauma is reported. The clinical and radiolocal observations are presented as well as the interest of this case in forensic medicine. A review of the legal aspects recalls the principles of imputability in cases of cancer and trauma. While malignant tumors discovered after renal trauma are often renal cancers, urinary tract tumors can also be revealed after renal trauma. This unfrequent circumstance of discovery underlines the importance of control urography in cases of renal trauma, of history taking (smoking), and of the requirement for follow-up investigations if intra-luminal urographic abnormalities persist without damage to the renal parenchyma on the CAT scan. PMID- 1940430 TI - [Apropos of the article: Low-pressure substitution ileo-cystoplasty after total cysto-prostatectomy]. PMID- 1940431 TI - Human melanocyte growth and differentiation: a decade of new data. PMID- 1940432 TI - Differential protection by two sunscreens from UV radiation-induced immunosuppression. AB - A controversy has arisen concerning the ability of sunscreens to protect mice from the immunosuppressive effects of UV radiation. We have assessed the photoprotection in hairless mice of two sun protection factor (SPF)15 sunscreens containing different UVB (280-320-nm) absorbers, namely, octyl-N-dimethyl-p aminobenzoate (o-PABA) or 2-ethylhexyl-p-methoxycinnamate (2-EHMC). Following three minimum erythemal exposures to UV radiation, both systemic suppression of contact hypersensitivity to 2,4-dinitrofluorobenzene and induction of susceptibility to transplanted UV radiation-induced tumor cells was established. Topically applied 2-EHMC sunscreen protected totally from both forms of immunosuppression, but the o-PABA sunscreen failed to protect, although both sunscreens were equally effective in protection from UV radiation-induced erythema and edema. PMID- 1940433 TI - Hypoxia upregulates the synthesis of TGF-beta 1 by human dermal fibroblasts. AB - In this report, we have investigated the secretion and synthesis of transforming growth factor-beta 1 (TGF-beta 1) by human dermal fibroblast cultures in response to hypoxia (2% oxygen), and have compared it to standard oxygen culture conditions (15% oxygen at the cell surface). Sandwich enzyme-linked immunosorbent assay (SELISA) showed a selective and progressive increase in secretion of the TGF-beta 1 isoform in response to hypoxia, up to ninefold after cultures were exposed to low oxygen for 72 h; TGF-beta 2 peptide levels were not increased. We then investigated the transcriptional regulation of the TGF-beta 1 gene in response to low and standard oxygen tensions. In the first 24-48 h, TGF-beta 1 mRNA levels decreased steadily in both oxygen environments. This mRNA decline continued for up to 72 h in standard oxygen but not in cultures exposed to low oxygen tension. At 72 h, steady-state TGF-beta 1 mRNA levels were 8 times greater in low compared to standard oxygen, and this increase was reversible upon re exposure of fibroblast cultures to standard oxygen tension for 24 h. Elevated TGF beta 1 m-RNA levels in both low and standard oxygen declined steadily and with the same half-life after the addition of actinomycin D, suggesting that hypoxia increased TGF-beta 1 transcription rather than mRNA stability. We conclude that low oxygen tension upregulates the synthesis of TGF-beta 1 by human dermal fibroblasts, and leads to increased secretion of this peptide. PMID- 1940434 TI - Elastin-associated microfibrils (10 nm) in a three-dimensional fibroblast culture. AB - The purpose of this study is to present a three-dimensional dermal fibroblast model. Skin fibroblasts cultured in this system deposit large amounts of collagen and microfibrils. Fibroblasts were seeded onto a nylon filtration mesh and incubated in the presence or absence of ascorbic acid. Collagen fibril formation was found in the presence of ascorbic acid whereas microfibril formation was seen independent of ascorbic acid supplementation. Immunoelectron microscopy revealed that microfibrils were labeled with fibrillin at 67 nm periodicity. Isolated microfibrils studied by rotary shadowing had a beaded appearance consisting of beads linked to each other by a filamentous structure. The spaces between the beads ranged from 10.00-33.33 nm, suggesting that these microfibrils may have an extension-contraction mechanism. Furthermore, the size and spacing of the beads were similar to that seen in microfibrils from tissues (measured after rotary shadowing). Fibroblasts cultured in a three-dimensional mesh represent an effective in vitro model with which to study microfibril formation. PMID- 1940435 TI - Effects of steroid, retinoid, and protease inhibitors on the formation of acantholysis induced in organ culture of skins from patients with benign familial chronic pemphigus. AB - Skin explants from two lesional areas and four normal-appearing areas of four patients with benign familial chronic pemphigus (BFCP) were organ cultured with and without various reagents. After 24-h culturing of involved skin with medium only, dissociation of keratinocytes, which was also observed prior to culturing, was exacerbated, and the epidermis became edematous, with a large section detaching from the dermis. These phenomena were not suppressed even when betamethasone, retinol acetate, or camostat mesilate (serine protease inhibitor) was added to the medium. On the other hand, in the cultures of uninvolved skin explants with medium only, widened intercellular spaces were observed 24-48 h after initiation of culture, and dissociation of keratinocytes and acantholytic clefts became apparent after 72 h. Such culture-induced acantholysis was almost completely suppressed by the addition of betamethasone, but not suppressed by the addition of retinol acetate, EDTA, N-ethylmaleimaide, or pepstatin A. Camostat and SBTI incompletely suppressed the acantholysis. These findings suggest the possibility that steroid may reduce blistering and that an organ culture of non lesional benign familial chronic pemphigus (BFCP) skin may be useful for clarifying the pathogenesis, as well as for discovering new drugs for the treatment of BFCP. Further experiments are required to clarify the role of serine proteases in the acantholysis in this disease. PMID- 1940436 TI - Reconstitution of the histologic characteristics of a giant congenital nevomelanocytic nevus employing the athymic mouse and a cultured skin substitute. AB - This study addresses the development of an animal model for human giant congenital nevomelanocytic nevi (GCNN). Skin grafts were made from 1) non involved split-thickness skin from a 12-month-old GCNN patient, 2) nevus split thickness skin from the same GCNN patient, 3) nevus full-thickness skin, and 4) cadaveric human split-thickness skin. For groups 1) and 2), human epidermal and dermal cells were enzymatically isolated and expanded in tissue culture. Composite grafts were made by placing the cultured dermal cells into a collagen glycosaminoglycan (GAG) matrix, followed by placement of the epidermal cells onto the opposite, laminated side of the matrix. All grafts were placed onto full thickness wounds of athymic mice and biopsies were obtained from 6 to 38 weeks later for light microscopy including S-100 immunoperoxidase staining, and electron microscopy. The GCNN cultured skin mice (group 2) developed black, raised skin in the healed wounds. None of the group 1 mice developed lesions, grossly or histologically. All of the nevus full-thickness mice retained the nevus grossly. Histopathologic examination at 38 weeks of the black, raised plaques of group 2 demonstrated a reconstituted dermis similar to group 3. Nevus cells were larger and more epithelioid in the upper dermis, as seen with true GCNN. These nevomelanocytes were not seen in the dermis at 24 weeks, suggesting that the nevus cells migrated from the epidermal component of the cultured graft to the dermis during this time frame (24-38 weeks). The melanocyte identity of these cells was confirmed with S-100 immunoperoxidase staining and electron microscopy. These findings are unique to this composite cultured graft system. The ability to culture specific types of melanocytes and place them int skin substitutes on athymic mice provides a basis for the study of GCNN and melanocyte biology in vivo. PMID- 1940437 TI - C-fos and c-jun proto-oncogene expression is decreased in psoriasis: an in situ quantitative analysis. AB - Psoriasis is a common, sometimes severe, non-malignant skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes. Because proto-oncogenes are implicated in both cell proliferation and differentiation, their expression could be modified in skin diseases such as psoriasis. The c-fos and c-jun proto-oncogenes, whose products associate to form a heterodimeric transcription factor, are among the first genes to be expressed when certain cells are stimulated to either proliferate or differentiate. Recent studies in our laboratory have shown that the c-fos proto-oncogene is highly expressed in normal human adult skin. In the present study, we used in situ hybridization with RNA to compare the expression and localization of c-fos and c-jun transcripts in 15 lesional and non-lesional psoriatic skin samples. Two clinical variants of psoriasis were studied: the most severe and chronic form or plaque-type psoriasis (N = 10) and rapidly resolutive guttate-type psoriasis (N = 5). Quantitative analysis was performed using a semi-automatic image analyzer and the "Starwise grain" software program. Our control samples included 10 normal skins and eight specimens from other benign hyperproliferative non-psoriatic skin diseases, consisting of three with inflammation (seborrheic dermatitis and atopic dermatitis), and 5 without inflammation (seborrheic keratoses). Control genes we used for in situ hybridization and RNA integrity were keratin 14, which is expressed in the epidermis and was normally expressed in all tissue analyzed, and ribosomal RNA. Our data showed that c-fos and c-jun were expressed to an equivalent extent, both spatially and quantitatively, in all specimens tested. Expression was significantly decreased in plaque-type but not in guttate-type psoriasis. It was also decreased in the three other benign inflammatory cutaneous hyperproliferative disorders, but not in the five non-inflammatory cases. These results were surprising because hyperproliferation was here associated with a decrease in proto-oncogene expression, thus suggesting that c-fos and c-jun do not play a crucial role in the control of keratinocyte proliferation in vivo. However, their reduced expression in some abnormally differentiated skins indicates that both c-fos and c-jun proto-oncogenes may play a key role in keratinocyte differentiation. Their altered expression correlated with severity of the disease and the presence of an inflammatory infiltrate. These data offer a new insight into the role and regulation of these proto-oncogenes in vivo in humans. PMID- 1940439 TI - Stimulation of collagen and glycosaminoglycan production in cultured human adult dermal fibroblasts by recombinant human interleukin 6. AB - Interleukin (IL) 6 is a pleiotropic cytokine synthesized by fibroblasts in response to many stimuli, including IL-1 beta. To evaluate the possibility that previously observed stimulation of fibroblast biosynthetic functions by IL-1 beta may be mediated by autocrine IL-6, we investigated the effect of recombinant human (rh) IL-6 on the connective tissue-related biosynthetic functions of three lines of cultured human adult dermal fibroblasts. We found that rhIL-6 mimicked some of the activities of IL-1 beta, as 24-96-h treatment of confluent fibroblast cultures with rhIL-6 caused concentration (10 to 1000 ng/ml)-dependent increases in the production of collagen and the glycosaminoglycans (GAG), hyaluronic acid and chondroitin-4/6-sulfates, but had little effect on fibronectin or total protein production. Although the effective stimulating concentrations of IL-6 were within the range (approximately 100 ng/ml) we found produced by rhIL-1 beta treated fibroblast cultures, rhIL-1 beta at 0.2-1.0 ng/ml induced significantly greater amounts of collagen and GAG than the maximum effective concentrations of IL-6. Moreover, an anti-rhIL-6 antibody, which effectively neutralized the fibroblast-stimulating activities of rhIL-6, only fractionally blocked the fibroblast-stimulating actions of rhIL-1 beta, suggesting autocrine IL-6 only partially mediates the effects of IL-1 beta on fibroblasts. Conversely, the fibroblast-stimulating effects of rhIL-6 are unlikely due to autocrine IL-1 beta, as an anti-rhIL-1 beta antibody had only minimal inhibitory action on rhIL-6 treated fibroblast cultures. Overall these results suggest that IL-6 could function as a paracrine/autocrine regulator of dermal fibrotic repair. PMID- 1940438 TI - Growth stimulation of human keratinocytes by tissue inhibitor of metalloproteinases. AB - Human recombinant tissue inhibitor of metalloproteinases (rTIMP) at 0.2-4.6 microM was found to stimulate the growth of normal human keratinocytes, in primary cultures on a plastic support, and to markedly increase their growth on a tridimensional culture system, the skin equivalent, as shown by histology, DNA measurements, and planimetry. In contrast, rTIMP had no effect on the growth of normal human fibroblasts. The growth of keratinocytes on extracellular matrix components produced by keratinocytes cultured in the presence or absence of rTIMP was similar, suggesting that rTIMP does not stimulate keratinocyte growth by modifying either the quantity or the composition of the extracellular matrix deposited. rTIMP was labeled with 125iodine in order to study its interaction with keratinocytes in culture. Binding of (125I) rTIMP to keratinocytes was found to be temperature and time dependent. Under steady-state conditions at 22 degrees C, one class of specific rTIMP binding sites was identified with KD of 8.7 nM and 135,000 sites/cell. Such findings are in keeping with the known potentiating effect of TIMP on erythroid precursors, and indicate that this protein has at least two distinct activities. PMID- 1940440 TI - Gene rearrangement studies in the diagnosis of primary systemic and nodular primary localized cutaneous amyloidosis. AB - Difficulties may arise in the diagnosis of patients with clinical features suggestive of plasma cell dyscrasia-related amyloidosis (amyloidosis L), but without evidence of a paraprotein. We have employed gene rearrangement methodology to demonstrate the clonality of bone marrow cells not only in a patient with myeloma-associated systemic amyloidosis, but also in a patient with "primary" systemic amyloidosis without overt myeloma or a detectable paraprotein. Furthermore, we have shown the clonality of the amyloid-producing plasma cells within a skin nodule of a patient with primary localized cutaneous amyloidosis; by contrast, clonal rearrangement was not detected in bone marrow cells from this patient. This finding provides definitive proof that organ-limited nodular primary localized cutaneous amyloid deposits arise in relation to cutaneous plasmacytomas. Gene rearrangement studies may enable early diagnosis and initiation of treatment in patients with systemic amyloidosis L, as well as their differentiation from patients with organ-limited nodular cutaneous amyloidosis, who do not require aggressive therapy. PMID- 1940441 TI - HLA DQB1*0301 allele is involved in the susceptibility to erythema multiforme. AB - Erythema multiforme (EM) is an acute, episodic inflammatory disorder of the skin and mucous membranes of various etiology that could be related to immunologic hypersensitivity response. EM has been previously reported to be associated with serologically defined HLA-DRw53 and DQw3 antigens. In this report, we reevaluate the role of HLA class II alleles in EM manifestations. With use of the polymerase chain reaction, followed by sequence-specific oligonucleotide hybridization, 35 unrelated Caucasian EM patients and 80 randomly selected healthy subjects were studied, and the DRB3, DRB4, DQA1, and DQB1 alleles were analyzed. The comparison of frequencies of these alleles indicates that (i) susceptibility to EM disease is more associated with the HLA-DQ than the HLA-DR subregions and (ii) that the DQB1*0301 is the most frequent allele among EM patients. Sixty-six percent of the patients had the DQB1*0301 allele compared to 31% of the controls (RR = 4.1; p less than 0.001). An even stronger DQB1*0301 association was found in the patient group with herpes-associated EM (76%; RR = 6.5; p less than 0.001). Our data demonstrate a clear association between an HLA-DQB1 allele and susceptibility to EM. PMID- 1940442 TI - Molecular cloning, occurrence, and expression of a novel partially secreted protein "psoriasin" that is highly up-regulated in psoriatic skin. AB - Analysis of the protein patterns of normal and psoriatic noncultured unfractionated keratinocytes has revealed several low-molecular-weight proteins that are highly up-regulated in psoriatic epidermis. Here, we have cloned and sequenced the cDNA (clone 1085) for one of these proteins that we have termed psoriasin. The deduced sequence predicted a protein of molecular weight of 11,457 daltons and a pI of 6.77. The protein co-migrated with psoriasin as determined by two-dimensional (2D) gel analysis of [35S]-methionine-labeled proteins expressed by RK13 cells transfected with clone 1085 using the vaccinia virus expression system. Analysis of the predicted sequence revealed a potential calcium-binding sequence of the EF-hand type, as well as the absence of a signal sequence at its amino terminal. Psoriasin is not related to other proteins that migrate closely in 2D gels (MRP 14, also known as calgranulin B, L1 and calprotectin; MRP 8, or calgranulin A and cystatin A or stefin A), and bears no significant sequence homology with any other protein of known primary structure. Increased expression of psoriasin mRNA in psoriatic keratinocytes was confirmed by Northern blotting and in situ hybridization. Psoriasin showed a restricted occurrence in fetal human tissues as determined by 2D gel electrophoresis. Of 21 tissues analyzed, only ear, skin, and tongue showed significant levels of this protein. Psoriasin was not detected in normal human fibroblasts, lymphocytes, endothelial cells and transformed epithelial cells of keratinocyte origin. Granulocyte extracts contained this protein suggesting that its overexpression by psoriatic keratinocytes may be linked to the inflammatory stimuli. PMID- 1940443 TI - Simple mucin-type carbohydrates in oral stratified squamous and salivary gland epithelia. AB - Simple mucin-type carbohydrate antigens, T, Tn, and sialosyl-Tn, have been found to be good markers of malignant transformation in several epithelial tissues as a result of incomplete synthesis with precursor accumulation. The T, Tn, and sialosyl-Tn antigens represent the initial, most immature glycosylation of serine and threonine amino acids of proteins. In normal adult cells these structures are generally masked by addition of further saccharides to form more complex structures. We analyzed simple mucin-type carbohydrates in human labial stratified squamous and minor salivary gland epithelia in order to define the glycosylation pattern in normal cells in relation to epithelial differentiation and maturation. A panel of monoclonal antibodies with well-characterized specificity for T, Tn, sialosyl-Tn and the histo-blood group H and A variants hereof were used in immunohistology of sections from 30 individuals with known ABO, Lewis, and secretor status. In stratified epithelium the sialylated T structure was confined to cell membranes of immature basal cells, whereas the H and A variants were observed on cell membranes of more mature parabasal and spinous cell layers. Furthermore, superficial spinous cells produced a fine granular cytoplasmic staining for Tn and sialosyl-Tn antigens. In minor salivary glands mucous cells expressed Tn and sialosyl-Tn as well as the H and A variants in the area of the nucleus, whereas T and the H variant were found in duct cells and unsubstituted T antigen in myoepithelial cells. These results indicate that incomplete synthesis, i.e., deletion of sialyltransferases and/or histo-blood group ABH transferases, may result in accumulation of T, Tn, and sialosyl-Tn antigens in oral epithelia, thus offering a baseline for further studies of changes in premalignant and malignant oral epithelia. PMID- 1940444 TI - Expression and characterization of membrane co-factor protein (MCP) in human skin. AB - Membrane co-factor protein (MCP; CD46) is an integral membrane protein with molecular weight (MW) of the two species of 63 kD and 55 kD, and regulates autologous complement activation, with the activity of factor I cofactor. The quantity of each species is genetically regulated, and two codominantly inherited allelic variants account for the three phenotypic patterns. By immunohistochemical study, MCP was found both in the intercellular spaces of the epidermis and on the endothelial cells in the dermis of normal human skin in vivo. The intensity of the staining pattern was higher in the basal layer than in the granular layer. By Western blot analysis with use of a monoclonal antibody, MCP in the epidermis appeared as several bands ranged from 60-50 kD, with a major band of 56 kD, which was different from those in either polymorphonuclear cells, platelets, and cultured keratinocytes. No other variants were found in the epidermis obtained from skin of 20 normal humans. Complement activation in human skin may be regulated at several steps, including DAF and HRF20, thereby protecting cells from autologous complement attack. PMID- 1940445 TI - Characterization of bullous pemphigoid antibodies by use of recombinant bullous pemphigoid antigen proteins. AB - The seroreactivity of patients with bullous pemphigoid (BP) to recombinant proteins representing sequences in the carboxyl domain of the murine 230-kD BP antigen (BPA) was determined. Sera from 133 patients with BP, 20 patients with pemphigus, and 21 normal subjects were examined by Western blotting by using two recombinant proteins: RP120 (MW = 120 kD), representing the C-terminal half of the 230-kD BPA, and RP60 (MW = 60 kD), representing the C-terminal quarter. These RP120 and RP60 were recognized by 84% and 61%, respectively, of the BP sera that reacted with the 230-kD BPA in epidermal extract, and not by any of pemphigus or normal sera. Furthermore, these RP120 and RP60 were not recognized by any BP sera that reacted only with the 170-kD BPA, which is known to be another major BPA. These findings indicate that one or more of the major antigenic regions localizes in the carboxyl-half domain of the 230-kD BPA, and also suggest that the 230-kD BPA may be distinct from the 170-kD BPA. PMID- 1940447 TI - Increase of sialylated tetraantennary sugar chains in parallel to the higher lung colonizing abilities of mouse melanoma clones. AB - The N-linked sugar chains of melanoma cell membrane from five murine B16 melanoma clones (F1, F10, BL6, W1-4, and C4-1) with different degrees of metastatic abilities after intravenous and intrafootpad injections were released quantitatively as oligosaccharides by hydrazinolysis, and their structures were analyzed by serial lectin column chromatography, Bio-Gel P-4 column chromatography, and sequential glycosidase digestion. Sugar chain structures of each clone have shown to consist of the same elemental oligosaccharides, but to differ in their percent compositions. More than 84% of the neutral oligosaccharides were high mannose-type sugar chains. Most complex-type sugar chains were sialylated, of which the major structure was tetraantennary sugar chain. Highly lung-colonizing F10 cells had 1.4 and 1.7 times more non-repeated tetraantennary sugar chains than moderately colonizing F1 and C4-1 cells, respectively, and 2.5 times more than poorly colonizing W1-4 cells. BL6 cells, which are also highly lung-colonizing, had 1.5 and 1.9 times more non-repeated tetraantennary sugar chains than F1 and C4-1 cells, respectively, and 2.8 times more than W1-4 cells. These results suggest that increase of sialylated tetraantennary complex-type sugar chains without N-acetyllactosamine repeating units of B16 melanoma cells might correlate with the higher lung-colonizing ability after intravenous injection. PMID- 1940446 TI - Effects of ultraviolet B light on cutaneous immune responses of humans with deeply pigmented skin. AB - The incidence of skin cancers of the basal and squamous cell types is extremely low among genetically black-skinned human beings, whereas these types of skin cancers are common among Caucasians, especially those who live in geographic areas of high sun exposure. Ultraviolet B light (UVB) is thought to be the primary oncogenic agent in sunlight. We have recently demonstrated that acute, low-dose exposure of Caucasian skin to UVB impairs the induction of contact hypersensitivity to dinitrochlorobenzene (DNCB) in approximately 40% of normal individuals. Importantly, this trait--termed UVB susceptibility--was found to be a characteristic of virtually 100% of patients with a history of biopsy-proved skin cancer, implying that UVB susceptibility may be a risk factor for this disease. Because melanin pigment is thought to be protective of some of the deleterious effects of UVB radiation, we have examined the capacity of a low-dose regimen of UVB to alter induction of contact hypersensitivity in individuals with genetically melanized or heavily tanned skin. Our results indicate that UVB radiation depletes heavily pigmented skin of Langerhans cells, just as it does in Caucasian skin. Moreover, UVB-susceptibility exists as a polymorphic trait in individuals with genetically determined black skin, as well as in individuals with heavily tanned skin, and the incidence of this trait is similar to that found among normal Caucasian subjects. Thus, melanin does not appear to protect against the deleterious effects of an acute, low-dose regimen of UVB on induction of cutaneous immunity, and the UVB susceptibility trait is equally well represented in both black- and Caucasian-skinned individuals. We conclude that although UVB susceptibility may function as a risk factor for skin cancer in Caucasians, it does not function similarly in black-skinned human beings, probably because melanin effectively protects against the mutagenic properties of UVB radiation. PMID- 1940448 TI - Autoantigens for IgA anti-intercellular antibodies of intercellular IgA vesiculopustular dermatosis. AB - A new disease characterized by the presence of in vivo bound and/or circulating IgA anti-intercellular (IC) antibodies has recently been identified. We propose the term intercellular IgA vesiculopustular dermatosis (IAVPD) for this entity, which seems to be divided clinicopathologically into at least two distinct subtypes: intraepidermal neutrophilic IgA dermatosis (IEN type) and subcorneal pustular dermatosis-like cases (SPD type). Using immunoblot technique, we examined the antigen substances for the IgA anti-IC antibodies in the sera from one Japanese patient with IEN type of IAVPD and three Japanese patients with SPD type. A serum from a patient with IEN type reacted exclusively with a 120-kD protein in both the normal human skin extract and the bovine desmosome sample. Sera from three patients with SPD type reacted specifically with a doublet of 115 kD and 105-kD proteins, which appeared to be identical to desmocollins I and II, well known desmosomal core proteins, in the bovine desmosome sample. IgA antibody from our patients with IAVPD bound to neither pemphigus vulgaris antigen nor pemphigus foliaceus antigen. From these results, we suggest that IAVPD is different from pemphigus and is heterogeneous in terms of the antigens to which IgA autoantibodies bind. PMID- 1940449 TI - Adverse effect of lignocaine (lidocaine) on skin destined for keratinocyte culture. PMID- 1940450 TI - Can some melanotropins modulate keratinocyte proliferation? PMID- 1940451 TI - Liposomal hamycin: reduced toxicity and improved antifungal efficacy in vitro and in vivo. AB - Hamycin has been used to treat a variety of yeast and other fungal infections by oral, topical, and intraperitoneal routes. However, its parenteral use has been reported to be associated with high toxicity. Multilamellar liposomes composed of dimyristoyl phosphatidyl choline, dimyristoyl phosphatidyl glycerol, and various amounts of cholesterol were used as drug carriers for hamycin. The antifungal activity of hamycin was maintained after liposome encapsulation (MIC range, 0.6 1.2 micrograms/ml), and toxicity was reduced in vitro and in vivo as the concentration of cholesterol was increased to an appropriate ratio. Mice were treated with various doses of free or liposomal hamycin 2 days after infection. Although free drug did not significantly improve survival, liposomal hamycin at an equivalent dose (0.6 mg/kg) increased the survival from 18 to 38 days. Higher doses (1.2 and 1.8 mg/kg) showed further improvement in survival and reduction in numbers of colony-forming units in the kidneys. Liposome encapsulation resulted in improved therapeutic index of hamycin. PMID- 1940452 TI - Clinical evaluation of the cysticercosis enzyme-linked immunoelectrotransfer blot in patients with neurocysticercosis. AB - During the 3 years that the enzyme-linked immunoelectrotransfer blot (EITB) assay for the diagnosis of human cysticercosis has been in use at the Centers for Disease Control, 50 patients with both pathologically confirmed neurocysticercosis and computed tomographic (CT) or magnetic resonance imaging (MRI) scan results were identified. Of 32 patients with two or more lesions, 94% had detectable antibodies by EITB compared with 28% of 18 patients with single lesions. Patients with only calcified cysts (single or multiple) were less likely to have EITB-positive results than were those with noncalcified, enhancing lesions. Antibody was detectable more frequently in serum than in cerebrospinal fluid, regardless of the number or apparent condition of the cysts. These findings confirm that the EITB assay for cysticercosis antibodies is highly sensitive in patients with multiple, enhancing intracranial lesions but is less sensitive in patients with single lesions and in those with calcified lesions. PMID- 1940453 TI - Trichinella infection in travelers. AB - To define the incidence of trichinosis associated with foreign travel and characterize the epidemiologic and clinical features of cases acquired abroad, all case report forms submitted to the Centers for Disease Control through state health departments and the National Morbidity Reporting System from 1975 to 1989 were reviewed. Twenty-six cases of travel-associated trichinosis were identified during that period. Most reported cases (73%) occurred between 1982 and 1987. Affected patients were more likely to have traveled to Mexico and Asian countries (65%). Reported high-risk behaviors included consumption of undercooked pork products, use of unsanitary cooking practices, and importation of potentially contaminated meat products into the United States. Trichinosis should be considered in the differential diagnosis of eosinophilia in travelers returning from abroad. Pretravel counseling that includes information concerning the risk of eating improperly prepared meat products may help future travelers minimize the risk of acquiring this illness. PMID- 1940454 TI - A "sentinel" technique for monitoring viral aerosol contamination. PMID- 1940455 TI - Cytokine levels in serum and cerebrospinal fluid in patients with chronic fatigue syndrome and control subjects. PMID- 1940456 TI - DNA amplification of human T lymphotropic virus type I (HTLV-I) proviral DNA in breast milk of HTLV-I carriers. PMID- 1940457 TI - Human T cell lymphotropic virus type II infection in Argentina. PMID- 1940458 TI - Natural killer cytotoxic test in the presence of phytohemagglutinin distinguishes between patients in the early and late stages of human immunodeficiency virus infection. PMID- 1940459 TI - Analysis of survival in 281 patients with AIDS in southern France. PMID- 1940460 TI - Growth of Vibrio vulnificus in serum from alcoholics: association with high transferrin iron saturation. PMID- 1940461 TI - Lymphocytes from the site of disease in reactive arthritis indicate antigen specific immunopathology. PMID- 1940462 TI - Tumor necrosis factor in paracoccidioidomycosis patients. PMID- 1940463 TI - Ivermectin therapy: a 5-year follow-up. PMID- 1940464 TI - Lack of evidence for a causal association between parasitic infections and acute appendicitis. PMID- 1940465 TI - In vitro inhibition of hepatitis B virus replication by 2',3'-dideoxyguanosine, 2',3'-dideoxyinosine, and 3'-azido-2',3'-dideoxythymidine in 2.2.15 (PR) cells. AB - Hep G2-derived hepatoblastoma cells (2.2.15), which actively produce hepatitis B virus (HBV), were cultured in the presence of 2',3'-dideoxyguanosine (ddG), 2',3' dideoxyinosine, or 3'-azido-2',3'-dideoxythymidine (AZT). ddG was the most potent agent. It diminished viral replication by up to 95%, as assessed by the amount of episomal HBV DNA, without impairing cellular growth. AZT was the least effective against HBV. Northern blot analysis revealed no apparent difference in the pregenomic viral RNA profile, suggesting that these dideoxynucleosides suppress reverse transcription in the replicative cycle of HBV. The effect of varying the time of drug exposure showed that these agents can suppress HBV replication even when added late in culture. HBV replication in another 2.2.15 cell population of the same lineage was affected by ddG differently, which may enable the investigation of phenotypic or genetic alterations during culture. The present data suggest that some 2',3'-dideoxynucleosides can exert a potent antiviral activity against HBV in vitro, at least under certain circumstances, although the data do not prove that any of these agents have utility in patients with hepatitis. PMID- 1940466 TI - In vivo stability of heterogeneous expression classes in clinical isolates of methicillin-resistant staphylococci. AB - To define the stability of methicillin-resistant Staphylococcus aureus (MRSA) in vivo, 22 isolates collected at one New York institution in 1989 and 1990 were studied. All 22 belonged to one of two distinct methicillin-resistant phenotypes (class 3 or 2), which were precisely identified as belonging to two distinct genotypes. Genotypic classification was based on restriction analysis of chromosomal DNA with EcoRI and HindIII and Southern analysis of ClaI digests using two DNA probes. One was specific for the mec gene; the other was specific for transposon Tn554. The findings suggest that the MRSA isolates studied were representative of two genetically distinct MRSA "clones," each with a unique strain-specific methicillin-resistant phenotype that is stable under the conditions of invasive disease, carriage, and spread from patient to patient. PMID- 1940468 TI - Hyperendemic shigellosis in the United States: a review of surveillance data for 1967-1988. AB - In 1988, 22,796 Shigella isolates were reported to the Centers for Disease Control, the highest number since national surveillance was begun in 1967. From 1986 to 1988, isolation rates increased from 5.4 to 10.1 per 100,000 persons. Increased isolation of Shigella sonnei, primarily among children and young women, occurred throughout the United States in a manner similar to the nationwide increase that occurred during the early 1970s. The highest rates during 1987-1988 were reported from countries with relatively high proportions of urban, ethnic ethnic minority, and poor residents, groups traditionally at high risk. The greatest percentage increases in isolation rates, however, occurred in relatively wealthy counties with predominantly white residents. Between 1967 and 1988, the proportion of Shigella species isolated from persons greater than or equal to 20 years of age increased 118%, while the proportion of the resident population in this age group increased only 16%. These data indicate a shift toward increased infection at older ages and the potential for periodic hyperendemic rates of shigellosis nationwide, which may be due to changing levels of immunity to S. sonnei. PMID- 1940467 TI - Triple-combination penicillin-vancomycin-gentamicin for experimental endocarditis caused by a moderately penicillin- and highly glycopeptide-resistant isolate of Enterococcus faecium. AB - An in vitro bacteriostatic synergy between beta-lactam and glycopeptide antibiotics has been recently described against isolates of Enterococcus faecium moderately resistant to penicillin and highly resistant to vancomycin. The relevance of this synergy in a rabbit endocarditis model was evaluated. Penicillin was tested at low- (LoD) and high-dose (HiD) regimens, alone or combined with vancomycin and/or gentamicin. Compared with controls, after a 5-day treatment: LoD penicillin, vancomycin, gentamicin, LoD penicillin plus gentamicin or vancomycin, and vancomycin-gentamicin were not effective; LoD penicillin vancomycin caused a small reduction of bacterial titers in vegetations that was strongly enhanced by adding gentamicin; HiD penicillin-gentamicin, the most effective regimen, was not significantly better than LoD penicillin-vancomycin gentamicin. These results suggest that the relative in vivo inefficacy of penicillin-vancomycin might be related to the fact that this combination was poorly bactericidal, and the triple combination of LoD penicillin-vancomycin gentamicin or the combination of HiD penicillin-gentamicin should be considered in the treatment of serious infections due to beta-lactam- and glycopeptide resistant enterococci. PMID- 1940469 TI - Oral aminoglycoside and ofloxacin therapy in the prevention of gram-negative sepsis after irradiation. AB - To investigate whether oral gentamicin or ofloxacin therapy protects against gram negative sepsis after irradiation, B6D2F1 mice were exposed to 7.5 Gy of radiation from 60Co, infected with 10(7) Pseudomonas aeruginosa or Klebsiella pneumoniae orally 3 days after irradiation, and treated with oral (15 mg/kg/day) or intramuscular (im; 7.5 mg/kg/day) gentamicin or oral (40 mg/kg/day) ofloxacin. For P. aeruginosa, gentamicin therapy was started orally 10 and 24 h and im 24 h after inoculation. For K. pneumoniae, gentamicin was started orally 24, 48, and 72 h and im 24 h after inoculation; ofloxacin was started 24 h after inoculation. Mice that received oral gentamicin early (10 h for P. aeruginosa, 24 h for K. pneumoniae), im gentamicin, or oral ofloxacin showed significantly (P less than .05) reduced colonization, translocation, and mortality compared with mice that received oral gentamicin late. These data support the use of selective antimicrobial therapy to reduce colonization, translocation, and mortality from gram-negative bacteria in irradiated animals. PMID- 1940470 TI - Progressive disseminated infection with Mycobacterium avium complex after intravenous and oral challenge in cyclosporine-treated rats. AB - Male Sprague-Dawley rats, immunosuppressed with cyclosporine (CsA), developed disseminated infection after intravenous or oral challenge with Mycobacterium avium complex (MAC). Disseminated infection leading to bacillemia could be established after intravenous inoculation with as few as 5 x 10(3) organisms. When CsA was not given or when CsA was stopped 1 month after infection, animals cleared the bacilli from blood and tissue. Animals developed disseminated infection after oral challenge with as few as 10(6) organisms. Persistent bacillemia occurred when organisms in the spleen exceeded 10(7). Differences in virulence among strains were observed. Infected tissues showed histopathologic changes similar to those seen in patients with AIDS. The CsA-treated rat is a new model that appears useful for studies of the virulence of MAC strains and the pathogenesis of disseminated MAC infection. PMID- 1940471 TI - Candida albicans stimulates endothelial cell eicosanoid production. AB - The response of human umbilical vein endothelial cells to invasion by Candida species was examined in vitro. Live Candida albicans caused significant endothelial release of eicosanoids, mainly prostaglandins. Since prostaglandin I2 (PGI2) is an important prostaglandin produced by endothelial cells, factors influencing its release were studied. The ability of different strains and species of Candida to induce endothelial PGI2 release was closely related to their capacity to injure the endothelium (r = .99). C. albicans was the only species tested that either stimulated PGI2 release or damaged the endothelial cells; only this organism possessed detectable phospholipase activity. Candida glabrata and Candida tropicalis had no phospholipase activity and neither increased PGI2 release nor caused significant endothelial damage. Close proximity with germinated C. albicans was required for endothelial injury and PGI2 release. The ability of C. albicans to stimulate endothelial cells may have important implications in regulating neutrophil activities against organisms that interact with endothelial cells. PMID- 1940472 TI - Acquired immunity to systemic candidiasis in immunodeficient mice. AB - Twenty-seven percent of beige-athymic (bg/bg nu/nu) mice died of systemic candidiasis 7-20 weeks after gastrointestinal tract colonization with Candida albicans. Conversely, beige-euthymic (bg/bg nu/+) mice colonized with C. albicans for a similar time period did not die or develop systemic candidiasis. C. albicans-colonized bg/bg nu/+ mice, but not bg/bg nu/nu mice, developed C. albicans-specific T cell-dependent antibody- and cell-mediated immune responses, indicating that T cell-dependent responses might explain the acquired resistance of bg/bg nu/+ mice to systemic candidiasis. Colonization with C. albicans enhanced the resistance of T cell-competent bg/bg nu/+ mice, but not bg/bg nu/nu mice, to systemic candidiasis. T cell-mediated immunity activated after mucosal colonization with C. albicans plays an important role in resistance to systemic candidiasis. PMID- 1940473 TI - Experimental fusarial hyalohyphomycosis in a murine model. AB - The pathogenicity of two clinical strains of Fusarium solani was studied in normal and transiently neutropenic outbred CF1 and CD1 male mice. Three inocula (5 x 10(5), 1 x 10(6), and 5 x 10(6) spores/animal) were tested. Groups of 10 mice each were injected with a single intravenous dose of one inoculum. Mortality correlated with the dose of inoculum, as survival was significantly shorter in mice injected with 5 x 10(6) cfu/mouse than in mice that received 1 x 10(6) or 5 x 10(5) cfu/mouse (P less than .001). Necrotizing abscesses with acute branching septate hyphae, neutrophil and macrophage infiltration, and hemorrhage were observed. The median survival of neutropenic mice was shorter than that of normal mice (P less than .001). Neutropenic mice did not show evidence of an inflammatory cellular reaction and exhibited significantly higher numbers of fungi per gram of infected tissue (P less than .001). Intact host defenses in normal mice were able to confine the infection to the kidneys after initial dissemination. In contrast, disseminated infection persisted in most organs in immunosuppressed animals. PMID- 1940474 TI - Development of immunity against Plasmodium falciparum malaria: clinical and parasitologic immunity cannot be separated. AB - A total of 1622 individuals of all ages living under conditions of continuous malarial transmission in Liberia were enrolled in a cross-sectional study of parasite rates, positive parasite densities, and body temperatures. The age specific Plasmodium falciparum-positive parasite densities were greatest at ages 0.5-1.0 year, then slowly declined into adulthood. The age-specific mean body temperature at parasite isodensity showed a steady decline even in the oldest age group. The results do not support the hypothesis that adults have higher body temperatures at a given parasite density than do children with the same parasite density. The age-specific P. falciparum parasite density for specific isotemperatures showed that a subgroup of children in the age group 0.5-1.0 year had low temperatures (less than 36.5 degrees C) despite high parasite densities. This indicates that low body temperature should be investigated further as a possible indicator of serious malaria in young children. Parasitologic and clinical immunity develops concomitantly and cannot be separated. The findings do not support the hypothesis that a special "anti-disease" immunity exists independently of parasitologic immunity. PMID- 1940475 TI - Lack of detection of human immunodeficiency virus in persistently seronegative homosexual men with high or medium risks for infection. AB - Some studies have suggested that seronegative homosexual men who have practiced high-risk sexual behavior can carry the human immunodeficiency virus (HIV) in a silent state, detectable only by polymerase chain reaction (PCR) or selective viral culture. To assess this concept, blood specimens were studied from 59 homosexual men with recognized risk behaviors: unprotected anal receptive intercourse at least once and many lifetime sex partners. After extensive virologic studies and PCR analysis, only one virus-positive, antibody-negative individual was identified. These findings indicate that HIV virus-positive, seronegative individuals are rare. PMID- 1940476 TI - Absence of chronic human immunodeficiency virus infection without seroconversion in intravenous drug users: a prospective and retrospective study. AB - It has been reported that human immunodeficiency virus type 1 (HIV-1) infection may exist in persons without specific antibodies for years. To measure the frequency of a silent carrier state, a study was conducted in a cohort of 124 intravenous drug users (IVDUs) without anti-HIV-1 antibodies. All the participants had engaged in high-risk behavior for HIV-1 transmission for a number of years until 1987 or later. Samples were analyzed at 6-month intervals for the presence of HIV-1 provirus using DNA amplification and for the appearance of anti-HIV-1 antibodies. HIV-1 provirus and antibodies were undetectable in 122 participants, whereas seroconversion was observed in 2. In one of these, both amplified HIV-1 pol gene segment and anti-HIV-1 antibodies were detected simultaneously, and in the other, provirus was detected 1 month before seroconversion. This study suggests that long-term HIV-1 infection without anti HIV-1 antibodies is rare and that repeated antibody testing is sufficient to determine the HIV-1 status of a person no longer at high risk for HIV-1 infection. PMID- 1940477 TI - Virulence of rimantadine-resistant human influenza A (H3N2) viruses in ferrets. AB - The influence of rimantadine-resistance mutations on the virulence of human H3N2 viruses in ferrets was examined. The similarities in virulence of the drug resistant mutants with single amino acid substitutions at three different locations, 27, 30, and 31, within the M2 sequence and their corresponding sensitive wild-type isolates contrasted with differences in virulence between the three pairs of viruses. These data provide further evidence that rimantadine resistant viruses that emerge during treatment of patients with the drug are unaltered both in their growth characteristics and virulence. PMID- 1940478 TI - Intestinal secretory immune response to infection with Aeromonas species and Plesiomonas shigelloides among students from the United States in Mexico. AB - Intestinal secretory IgA (sIgA) response or lack of response among adults in Mexico with diarrhea was used as an indicator of enteropathogenicity of Aeromonas species and Plesiomonas shigelloides. sIgA was extracted from stool specimens obtained at day of presentation and 5 days later. Total sIgA was standardized, and specific sIgA titer against the organism being shed by each patient was determined. Western blotting was used to determine which microbial antigens elicited an intestinal sIgA response. Of 12 subjects shedding Aeromonas sobria or Aeromonas hydrophila, 11 had a fourfold or greater sIgA titer rise against the infecting strain. Western blotting showed that somatic lipopolysaccharides were the immunodominant antigens. No sIgA titer rises were detected among two patients shedding Aeromonas caviae or in 14 shedding P. shigelloides. This study provides further evidence of the significance of A. sobria and A. hydrophila as pathogens in acute diarrhea but raises additional questions about the role of P. shigelloides, at least in US adults with travelers' diarrhea. PMID- 1940480 TI - An ELISA for the detection of localized adherent classic enteropathogenic Escherichia coli serogroups. AB - An ELISA for the detection of classic enteropathogenic Escherichia coli (EPEC) serogroups was developed. It detected EPEC positive for localized adherence (LA) by HeLa cell assay and EPEC positive for EPEC adherence factor (EAF) by DNA probe assay. A specific antiserum was raised with LA+ EPEC strain E2348/69 (serotype O127:H6) by immunizing rabbits and then absorbing the antiserum with its LA- derivative, MAR20. The absorbed antiserum reacted specifically with all 90 strains of E. coli belonging to eight different EPEC serogroups that were LA+ by HeLa cell assay and EAF+ by DNA probe assay. All E. coli strains including EPEC serogroups that were LA- by HeLa cell assay and EAF- by DNA probe assay were also negative by ELISA. Thus the ELISA is 100% sensitive and specific in detecting LA+ classic EPEC serogroups. PMID- 1940479 TI - Reduction of oropharyngeal carriage of Haemophilus influenzae type b (Hib) in children immunized with an Hib conjugate vaccine. AB - The oropharyngeal carriage of Haemophilus influenzae type b (Hib) was studied among 725 healthy 3-year-old children who had or had not been immunized with an Hib conjugate vaccine. Oropharyngeal swabs were collected during the childrens' well-child visit to their local child health center. Fourteen (3.5%) of the 398 unvaccinated children were oropharyngeal carriers of Hib, whereas none of the 327 children who had received Hib conjugate vaccine carried Hib (P less than .001). Carriage rates of non-type b H. influenzae (19%) or Streptococcus pneumoniae (18%) were the same irrespective of the Hib vaccination status of the children. Thus Hib conjugate vaccine, unlike Hib polysaccharide vaccine, seems to be able to prevent oropharyngeal colonization by Hib. PMID- 1940481 TI - Mycobacterium leprae-induced interferon-gamma production by household contacts of leprosy patients: association with the development of active disease. AB - Identification of individuals at risk for developing leprosy and their early diagnosis are central to effective disease control. Lack of immunologic response to Mycobacterium leprae among persons exposed to the infectious agent may be predictive of susceptibility. M. leprae-induced interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells was used as a measure of immune responsiveness. Household contacts of multibacillary patients likely to be at risk of developing active disease were identified, and a preliminary analysis after 2 years of follow-up is presented. A persistent in vitro negative response to M. leprae was present in 34.6% of the contacts, and a decrease in IFN-gamma production was noted in 52.5%. Five contacts (6.41%) developed leprosy during follow-up and, as predicted, belonged to the group of individuals who were negative or showed reduced levels of IFN-gamma in response to the antigen. PMID- 1940482 TI - Endemic and epidemic aspergillosis associated with in-hospital replication of Aspergillus organisms. AB - When a new hospital opened in 1983, environmental culturing for Aspergillus organisms and surveillance for nosocomial aspergillosis cases were begun to characterize the relationship between environmental contamination and infection. Monthly air sampling demonstrated increasing concentrations of Aspergillus flavus and Aspergillus fumigatus to mean levels greater than 1 cfu/m3 during 1986-1987, accompanied by a progressive increase in incidence of aspergillosis to 1.2% in immunocompromised patients. This prompted an inspection that revealed heavy growth of Aspergillus organisms on air filters. Subsequent inspections of hospital wards showed small foci of A. flavus growth on other materials. Removal of the contaminated filters and improved environmental maintenance were associated with reduction in A. flavus and A. fumigatus to 0.01 cfu/m3 and a fourfold decline in aspergillosis incidence during the next 2 years. These findings, together with laboratory studies that showed aspergilli could proliferate on common hospital materials when moistened, indicate a need for careful environmental maintenance. PMID- 1940483 TI - Inappropriate pain management results in high jury award. PMID- 1940484 TI - Character of terminal illness in the advanced cancer patient. PMID- 1940485 TI - Validation of World Health Organization guidelines for cancer pain relief during the last days and hours of life. AB - The efficacy of the World Health Organization's guidelines for cancer pain relief was examined in 401 dying patients. At the time of death, only 3% of the patients experienced severe or very severe pain; whereas 52% had no pain at all, 24% experienced only mild or moderate pain, and 20% were unable to rate their pain intensity. Analgesic drugs were the mainstay of therapy during the last 24 hr of life, being administered by mouth in 47% and parenterally in 44% of the patients. Only 9% of the patients required no systemic analgesics. Nonopioid analgesics alone were effective in 5% and a combination of nonopioids and "weak" opioids were effective in 16% of the patients. In the remaining 70% of the patients "strong" opioids alone or in combination with nonopioid analgesics were necessary to achieve adequate pain reduction. Additional adjuvant drugs to treat special types of pain or other symptoms were prescribed in 90% of the patients. Nonpharmacological measures, such as radiotherapy, nerve blocks or neurosurgery played only a very minor role at this stage of the disease. This study shows that cancer pain can be treated satisfactorily until death. PMID- 1940486 TI - A clinical study on the use of codeine, oxycodone, dextropropoxyphene, buprenorphine, and pentazocine in cancer pain. AB - The authors report a prospective study on 944 cancer pain patients treated with one of the following opioids: codeine, oxycodone, dextropropoxyphene, buprenorphine, and pentazocine. Level of analgesia, duration of treatment, side effects, and drop out were evaluated for each drug. Twenty-four percent of the patients still benefitted from treatment at the fourth week of study, even if high drug dosages were not used. Pentazocine did not show an evident analgesic effect during the first 2 wk of treatment. The other opioids were found to be valid therapeutic instruments for chronic cancer pain control in a limited number of patients. PMID- 1940487 TI - The incidence of narcotic-induced emesis. AB - Epidemiologic studies of the incidence of emesis induced by narcotic analgesics are lacking. The histories of 260 cancer patients receiving oral narcotic analgesics prescribed at the Pain Clinic of our Institute from December 1988 to December 1989 were reviewed. Of the 260 patients, 120 were women, median age 61 (range 30-90) yr and 140 were men, median age 62 (range 30-82) yr. Nausea and vomiting associated with assumption of the various narcotics were buprenorphine 8.3% and 22.7%, morphine 18.3% and 28%, codeine 16.2% and 29.7%, and oxycodone 10% and 40%, respectively. Since the use of narcotic analgesics can effectively relieve pain and improve quality of life in cancer patients, it is important to be aware of the incidence of narcotic-induced emesis in order to use appropriate prophylactic antiemetic therapy. PMID- 1940488 TI - The reproducibility of bioavailability of oral morphine from solution under fed and fasted conditions. AB - The reproducibility in bioavailability of orally administered morphine (as a solution) under fed and fasted conditions was studied in 5 patients with chronic pain on three occasions over 1 yr (0, 6, and 12 mo). During each study period (i.e.. 0, 6, and 12 mo), patients received the 50 mg oral dose both in the fasted state (10 hr since food) and immediately after a high fat content breakfast, in randomly determined sequence. Frequent blood samples were collected for 10 hr after the dose. There was no significant difference in the maximum blood morphine concentration (Cmax) or the time to Cmax among the three study periods or between the fed and fasted states. Bioavailability, as assessed by log(AUC), was significantly greater in the fed compared to the fasted state (P less than .01) but did not differ over the three study periods (Two-factor analysis of variance). Intrapatient variability contributed 32% and 54% to total variation in log(AUC) under fed and fasted conditions, respectively. PMID- 1940489 TI - Pain and paresthesia in patients with healed burns: an exploratory study. AB - The present study was designed to examine the prevalence and characteristics of painful and paresthetic sensations in a group of patients with healed burns. Adult patients who had been hospitalized for burn injuries during a 7-yr period were contacted and given a structured interview that included a series of questions about their present condition. Patients' medical charts were reviewed to obtain relevant demographic and medical information. The results show that abnormal sensations in healed burns are frequently reported as long as several years after the injury. Of 104 patients interviewed 1 yr or more after a burn injury, 82% reported paresthetic sensations such as tingling, stiffness, cold sensations, and numbness; and 35% complained of pain in the scarred tissue. The prevalence of these sensations was not related to age, sex, or etiology of the burns, but was associated with burn size and skin grafting. The theoretical and clinical implications of these results are discussed with particular emphasis on the need to pursue research on the long-term adverse effects of burn injuries. PMID- 1940490 TI - Physician cancer pain education: a report from the Wisconsin Cancer Pain Initiative. AB - The Wisconsin Cancer Pain Initiative was established in 1986 to address the various public and professional barriers to cancer pain management. This report discusses the initiative's model for physician education, which includes increasing factual knowledge, legitimizing cancer pain as an important treatment priority, and developing clinical role models. Our progress in implementing this education model will be discussed. PMID- 1940491 TI - Urinary catheters in palliative care. PMID- 1940492 TI - The underutilization of oxycodone. PMID- 1940493 TI - Infectious mononucleosis presenting as a parotid mass with associated facial nerve palsy. AB - A case of infectious mononucleosis presenting as parotid lymphadenopathy and associated partial facial nerve palsy is described and the possible diagnostic confusion with a malignant neoplasm emphasised. Infectious mononucleosis and other viral diseases which caused facial nerve palsy are discussed and the literature reviewed. PMID- 1940494 TI - Pilomatrixoma in the oro-facial region. PMID- 1940495 TI - Osteopetrosis presenting with paroxysmal trigeminal neuralgia. A case report. AB - Osteopetrosis is a rare disease of unknown aetiology. The relentless bone growth may progressively obliterate the various craniofacial skeletal foramina leading to nerve compression and a diversity of neurological disorders. A case is reported of a 37-year-old woman who was seen because of frequent attacks of paroxysmal trigeminal neuralgia (PTN); other orofacial neurologic deficits and generalised craniofacial skeletal thickening. The prompt recognition and management of associated disorders such as PTN is emphasized. Despite the lack of definitive treatment modalities for both osteopetrosis and PTN, the patient's quality of life must be sustained. PMID- 1940496 TI - Sublingual adult rhabdomyoma. Report of a case. AB - A case of intraoral adult extracardiac rhabdomyoma is reported. There has been no recurrence in 4 years follow-up. We estimate this to be the 111th reported case of extracardiac rhabdomyoma, the 29th to present in the tongue and sublingual regions. PMID- 1940498 TI - Unusual dislocation of the temporo-mandibular joints. A case report. AB - A case of an unusual bilateral mediolateral dislocation of the mandibular joints is reported. The condyle of the laterally displaced side was additionally fractured at the neck. No other fractures were present. PMID- 1940497 TI - Facial fractures occurring in a medium-sized metropolitan area: recent trends. AB - A retrospective 3-year survey of 311 patients sustaining 564 facial fractures in a medium-sized metropolitan area is presented. Etiology, distribution and treatment of these facial fractures are reported and compared with earlier studies, where changing patterns of etiology and treatment were noted. Contemporary knowledge of facial injuries is important if diagnosis and treatment are to be accurate and treatment optimal. PMID- 1940499 TI - Bicoronal flap approach to the temporomandibular joints. AB - The bicoronal scalp flap provides an excellent approach to the temporomandibular joint, particularly in cases where bilateral operation is required. It is also indicated when wide exposure is required and when previous surgery may make more conventional techniques difficult. In this report, the anatomy and indications for this approach are reviewed, the operative technique is described and complications are discussed. PMID- 1940500 TI - Surgical orthodontic treatment of anterior skeletal open bite using small plate internal fixation. One to five year follow-up. AB - Thirty-eight patients with skeletal open bite were studied retrospectively to assess stability of surgical-orthodontic treatment when small plate internal fixation was used. 86% of the sample population showed stable clinical results. Follow-up was from 1-5 years. Only 1 patient experienced skeletal relapse (3%) and 5 patients (13%) dento-alveolar relapse. Fifty percent of relapses were due to transverse relapse of orthodontically expanded maxillary arches. No relapse was seen with surgically assisted orthodontic expansion or surgical expansion at the time of osteotomy. Stable results can be achieved in treating skeletal open bite when small plate internal fixation is used and proper consideration given to the cause of skeletal open bite when planning treatment. PMID- 1940501 TI - Osteosarcoma of the maxilla. Case report and ultrastructural study. AB - An osteosarcoma, occurring in the maxillary alveolar ridge of a 17-year-old girl is presented. The tumor consisted predominantly of pleomorphic, mainly osteoblast like and anaplastic cells. At the ultrastructural level the osteoblast-like cells were characterised by excentrically situated lobed nuclei, extensively swollen, dilated and rough endoplasmic reticulum (RER), polymorphism of mitochondria and sparse Golgi-systems. The undifferentiated cells were characterized by large, electron-lucent nuclei and paucity of non-dilated RER and mitochondria. The intercellular matrix contained collagen fibers with areas of focal collections of calcification. PMID- 1940502 TI - Malignant melanotic schwannoma of the oral cavity. AB - Intraoral malignant melanotic schwannoma is an extremely rare tumor. Two cases are presented, one occurring in the mandible of a 62-year-old man, the other in the maxilla of a 79-year-old man. The clinical presentation, light microscopic findings and immunohistopathological features are described. The difficulty of diagnosing this special tumor at initial presentation correctly, is discussed. PMID- 1940503 TI - Experimental transplantation of vascularized autologous and allogenic bone grafts for mandibular defects. Anatomical, immunological and surgical basis for vascularized bone transfer in the Gottingen minipig. AB - The Gottingen minipig serves as a suitable animal model for studying microsurgically reanastomosed iliac crest grafts for reconstruction of bone defects of the mandible. Because of the vascularization pattern of the hip bones of the Gottingen minipig, the cranioventral region of the ilium is especially suitable as a donor site. The separate vascularization of this area allows the excision of a bone block with sufficient volume, mechanical strength and a reliable vascular pedicle. The high degree of immunological variability of the minipigs demonstrated by isoelectric focusing and subsequent immunoblotting of lymphocyte membrane proteins offers possibilities for allogenic transplantation models. The surgical technique of harvesting and transplantation of the bone graft is described in detail. PMID- 1940504 TI - Increase of temperature during osteotomy. In vitro and in vivo investigations. AB - Direct temperature measurements using copper-constantan thermocouples were performed during in vitro and in vivo bone cuttings while the load of the oscillating saw and irrigation were varied. Very high temperatures during continuously applied load were observed. Consequent irrigation may reduce temperature elevation, but only intermittent sawing combined with irrigation diminishes temperature elevation adequately, which allows for an osteotomy without discernible bone damage. In practice, the available oscillating saws should be handled with great care, which implies that the osteotomy should be performed with maximum irrigation and intermittent use. PMID- 1940506 TI - Rapid heating: critical theoretical assessment of thermal gradients found in hyperthermia treatments. AB - There is increasing evidence that many hyperthermia failures are closely related to the large variability of temperatures found in the treatment field. These are linked to thermal gradients near the treatment boundary, vascular perfusion differences, localized cooling, and poor distribution of energy deposition in the tissues. One way of reducing the temperature gradients is to replace traditional heating treatments of 30-60 min by a rapid heating technique, in which the treatment time is a few seconds combined with higher treatment temperatures. The purpose of this paper is to model potential advantages of using various rapid heating protocols, and to compare them with traditional treatments. Theoretical models (in agreement with clinical treatments) suggest that traditional hyperthermia treatments often do not produce the necessary temperature homogeneity needed to kill the last malignant cells in the tumour due to cooler regions in the field. The simulations presented in this paper suggest that much shorter treatment times (1-10 s) should give significant improvements in the treatment field for both the temperature homogeneity and equivalent thermal doses. PMID- 1940505 TI - Design of intracavitary microwave applicators for the treatment of uterine cervix carcinoma. AB - A 915 MHz intracavitary applicator was designed to heat tumours in the cervical and upper vaginal regions. The applicator has a 3.5-turn helical coil wound around the distal 19 mm of a dielectric rod 43 mm long and 30 mm in diameter. For treating uterine cancer, a 2450 MHz, 4 mm diameter helical applicator was made by replacing 6 cm of the outer conductor of a coaxial cable with six turns of copper wire soldered to the outer conductor. The heating patterns were determined thermographically in a muscle phantom. The maximum heating rates were 0.42 and 0.83 degrees C/W-min, respectively, for the 915 and 2450 MHz applicators. Intracavitary temperature distributions in the upper vagina, cervix and uterus were measured at the surface of the applicators with thermocouples. The average temperature was 46.0 +/- 2.1 degrees C (S.D.) at mid-tumour and 44.5 +/- 0.8 degrees C at the tumour periphery. The maximum temperature, up to 51.5 degrees C, was measured at the surface of the cervical applicator. The majority of the patients (28/30) tolerated the investigational treatment without burns or pain. Rectal temperatures were also monitored. The location of the hot-spot (40.7 degrees C) in the rectum, 5-7 cm above the anus, corresponded to the tip of the cervical applicator (47.1 degrees C). PMID- 1940507 TI - Modified thermal clearance technique for determination of blood flow during local hyperthermia. AB - The thermal clearance method utilizes the rate of temperature decay after the applied power is turned off to estimate the local blood flow. A limitation of this method has been its inability to account for the contribution of thermal conduction to the rate of temperature decay. As a result, the blood flow is generally overestimated. A modification of the thermal clearance method is described in this paper which enables the conduction component to be determined. Profiles of the tissue temperature are obtained in three mutually orthogonal directions about the point where thermal clearance is measured. The Laplacian of the temperature is evaluated from these profiles by the method of finite differences. The tissue thermal conductivity is estimated from literature values. The greatest source of error is the uncertainty in the location of the washout point in each catheter. Strict thermometry requirements must be adopted to reduce the localization error to +/- 0.25 cm. The thermometry catheters should be orthogonal to within +/- 10 degrees and all three catheters should be in contact at the washout point. The methodology was tested in a phantom, studied by use of a computer model, and implemented in the clinic. The experimental error in the conduction component is typically 50%. The resulting error in the blood flow depends on the relative rates of energy removal by blood flow and thermal conduction. When perfusion is the dominant mode of energy removal, the resulting uncertainty in the blood flow is typically in the range 20-30%. PMID- 1940508 TI - Errors in the two-dimensional simulation of ferromagnetic implant hyperthermia. AB - An empirical power absorption formula developed by Haider et al. (1991) for thermally self-regulating nickel-silicon ferromagnetic seeds has been incorporated into a three-dimensional patient treatment planning programme to calculate the seed power absorption as a function of seed temperature. The programme has been used to evaluate systematically the accuracy of two- versus three-dimensional simulations for ferromagnetic implant hyperthermia. The results show that two-dimensional simulations can significantly overestimate temperatures. Consequently, three-dimensional simulations are necessary for accurate hyperthermia treatment planning. PMID- 1940509 TI - Effect of chronic thermotolerance on thermosensitization in Chinese hamster ovary cells studied at various temperatures. AB - The effect of chronic thermotolerance on the thermal responses of Chinese hamster ovary (CHO) cells to single and step-down heating was studied. Thermotolerance was induced by pre-heating exponentially growing cells at 39 degrees C for 9 h, followed by test treatments for variable times at temperatures ranging from 39 to 43 degrees C. In the temperature range studied, the heat sensitivity of thermotolerant CHO cells was characterized by an Arrhenius activation energy of Ea = 1175 +/- 40 kJ/mol. This value agreed well with Ea = 1180 +/- 45 kJ/mol measured after single heating, indicating that the induction of chronic thermotolerance did not affect the activation energy for cell killing by heat. Thermosensitization was studied after a priming treatment at 43 degrees C for 50 min followed by step-down heating at temperatures ranging from 39 to 43 degrees C. The temperature dependence of the thermal response after step-down heating was characterized by an activation energy of Ea = 490 +/- 17 kJ/mol. When the cells were pre-treated for 1-16 h at 39 degrees C prior to step-down heating (43 degrees C, 50 min, followed by graded exposure to 39-43 degrees C), the activation energy was gradually enhanced and approached Ea = 825 +/- 42 kJ/mol for 39 degrees C, 16 h. This change in Ea reflects the effect of thermotolerance on the priming treatment at 43 degrees C for 50 min, whereas the effect on the final test treatment resulted in a parallel shift of the Arrhenius curve without changing the slope, indicating that the effect of thermotolerance on the priming and the test treatment is expressed in the Arrhenius diagram in different ways. PMID- 1940510 TI - Oxidative stress as a precursor to the irreversible hepatocellular injury caused by hyperthermia. AB - Heat-induced hepatotoxicity accompanying hyperthermic liver perfusion was studied in the isolated, haemoglobin-free perfused rat liver. Trypan blue uptake, a sensitive indicator of cell death, was used to examine the relationship between the efflux of oxidized glutathione (oxidative stress), the appearance of cytosolic enzymes in the perfusate and cell death. Livers were perfused at 37, 42, 42.5 and 43 degrees C. The efflux of total glutathione (GSH) and oxidized glutathione (GSSG) increased with time and temperature. Differences between temperature groups were significant for both parameters for 37 versus 42, 42.5 and 43 degrees C (p less than 0.05). Temperature-related differences in GSH levels appeared at 15 min for 37 versus 42 degrees C and in GSSG levels at 30 min for 37 versus 42 and 42.5 degrees C. Biliary excretion of total GSH increased from 72 nmol at 37 degrees C to 144 nmol at 42 degrees C, 160 nmol at 42.5 degrees C and 124 nmol at 43 degrees C, which was significant for 37 versus 42 and 42.5 degrees C (p less than 0.05). The release of allantoin into the perfusate, a measure of purine catabolism and flux through xanthine oxidase, was increased at 42, 42.5 and 43 degrees C compared to 37 degrees C (p less than 0.05). Liver injury was assessed by measuring the release of asportate aminotransferase (AST) and lactate dehydrogenase (LDH) and uptake of trypan blue after perfusion at each temperature. There was a pronounced release of LDH and AST into the perfusate after 60 min of perfusion at 42, 42.5 and 43 degrees C, the levels of which were significantly different from the 37 degrees C mean level. There was no uptake of trypan blue after 60 min perfusion at 37 degrees C. Perfusion at 42, 42.5 and 43 degrees C resulted in the uptake of trypan blue in the pericentral areas, but the dye uptake was significant (p less than 0.05) compared to 37 degrees C at 42.5 and 43 degrees C only. These data show that heat induced pericentral cell death is minimal after 60 min at 42-43 degrees C, and that the biochemical process which occurred during this period suggest 'oxidative stress' as a causative factor in hyperthermic hepatotoxicity. In addition, this liver toxicity is probably related to xanthine oxidase activity or the depletion of GSH as the initiating event which leads to lipid peroxidation and cellular damage. PMID- 1940511 TI - Enhancement of sensitivity to hyperthermia by lonidamine in human cancer cells. AB - Human glioma (87MG) and squamous cell carcinoma of the head and neck UMSCC-1 were shown to be sensitized to hyperthermia by Lonidamine treatment before and during hyperthermia. The degree of thermal sensitization increased with increasing heating times and temperatures. In addition, the thermal sensitization by Lonidamine as well as cellular thermal sensitivity were dependent on pH and increased with the more acidic pH. Even though plateau phase cells were more thermally resistant than exponentially growing cells, Lonidamine treatment caused thermal sensitization under both conditions. These data show that Lonidamine may hold potential to enhance the effectiveness of hyperthermia in cancer treatment and that especially in tumours with low pH an enhanced therapeutic gain may be achieved. PMID- 1940512 TI - Thermal sensitivity of the murine CFU-S-12: role of environmental cells. AB - The hyperthermic sensitivity of the CFU-S-12 in bone marrow from normal and anaemic mice was determined. The terminal slope of the survival curves, demonstrated by the T0 values, does not significantly differ in the resting and active cycling stem cells. In the active cycling stem cells the initial shoulder region was less dominant compared with the resting stem cells. The difference in heat sensitivity between resting and active proliferating CFU-S-12 might be explained by a difference in the accumulation of damage before lethality becomes manifest. The difference in heat sensitivity appears to be independent of the environmental accessory cells, demonstrated by a similar hyperthermic effect of the purified stem cells from bone marrow and spleen and the stem cells in the total cell suspensions. Therefore the heat sensitivity of the haemopoietic stem cell is not mediated by a release of injurious substances from environmental heat damaged cells. The heat treatment does not result in a selection of macroscopic detectable colonies 12 days after inoculation, as is demonstrated by the same morphology of the spleen colonies from the stem cells before and after the hyperthermic treatment. PMID- 1940513 TI - [Ten years experience with the St. Jude Medical valve prosthesis for mitral valve replacement]. AB - During the 10-year period between 1980 and December 1989, isolated mitral valve replacement (MVR) with the St. Jude Medical (SJM) valve prosthesis was performed on 404 patients at our hospital, and a long-term postoperative follow-up was conducted. There were 161 males and 243 females ranged in age from 1 year to 73 years. Early operative mortality was 5.2%. Follow-up period for 383 patients who discharged from the hospital was 1970.7 patient-years. Twenty of these patients died during the follow-up period, and a late mortality rate was 5.2%. During 10 years, thromboembolic event occurred in 8 patients. Four patients had anticoagulant-related bleeding, 4 had paravalvular leak, and 5 underwent re operations. There was neither structural valve failure nor prosthetic valve endocarditis. Therefore, the actuarial survival rate and the valve-related death free rate at 10 years were 83.2%, and 96.8%. Of the patients who survived, New York Heart Association class improved significantly (93% in classes II and III preoperatively and 71% in class I postoperatively). Linearized rates for thromboembolism, anticoagulant-related bleeding, and hemolysis were 0.41%, 0.20% and 0.36%/100 patient-years, respectively. The actuarial estimate of incidence free from all complications was 92.0% at 10 years. On the basis of this 10 years' experience, we believe that the SJM valve prosthesis is an excellent mechanical prosthesis for mitral valve replacement, in terms of hemodynamic performance and low thrombogenicity in patients receiving anticoagulants. PMID- 1940514 TI - [Analysis of flow cytometric nuclear DNA content of the thymoma and its relationship to malignant intensity]. AB - Determination was made of the nuclear DNA content of paraffin-embedded specimens of resected thymoma using flow cytometry in 39 patients. Relationships among nuclear DNA content, clinicopathological findings and prognosis were studied. The frequency of DNA aneuploid tumors was 30.8%, 6.7% in stage I (15 patients), 28.6% in stage II (7 patients), 44% in stage III (9 patients) and 62.5% in stage IV (8 patients) according to Masaoka's classification, indicating more in increase with advancing stage and significant (p less than 0.05) more increase invasive thymoma than in noninvasive thymoma. The 5 year and 10 year survival rates of DNA diploid tumors were each 94%, while DNA aneuploid tumors, 75% and 45%. Patients with DNA aneuploid tumors showed less favorable prognosis than those with DNA diploid tumors. Similar results were found in patients with invasive thymoma and in those on whom subtotal or partial resection were performed. The present results indicate DNA aneuploid tumors to have greater malignant intensity than DNA diploid tumors in resected thymoma. Flow cytometric nuclear DNA content analysis provides useful biological data and new indices for evaluating the malignancy of resected thymoma. PMID- 1940515 TI - [Changes of hypothalamo-pituitary-thyroid function after open heart surgery- especially evaluated by TRH test]. AB - Changes of pituitary and thyroid functions after operation were studied in the cases with cardiopulmonary bypass (ECC group) and without bypass (Control group). To know mechanisms of these changes, reaction of hypothalamo-pituitary-thyroid axis by using thyrotropin-releasing hormone (TRH) test and influence of serum cortisol level were examined. Serum concentrations of free T3, free T4 and TSH decreased after open heart surgery. The levels of TSH and free T4 were recovered at the second or third post operative day in Control group, but remained low level at the third POD in ECC group. The level of free T3 continued low level at the 7th POD. The feedback mechanism of the hypothalamo-pituitary-thyroid system was not seen in this series. The response of TSH and free T3 due to TRH test decreased in ECC group, and it was suppressed more clearly in the cases of longer bypass than in those of shorter ones. Serum cortisol level was significantly increased at the 3-hours after the operation in ECC group, and was more increased in the cases of longer bypass than in those of shorter ones. The results indicate that the pituitary and thyroid function on the post bypass period remains euthyroid sick syndrome and hypothalamo-pituitary axis remains suppressed state. Those phenomenon suggest that TRH test may be useful in evaluation of the intensity of surgical stress, especially in those who undergo the cardiopulmonary bypass. PMID- 1940516 TI - [Evaluation of cardio-pulmonary function for lobectomy under the condition of selective pulmonary arterial occlusion test (SPAO)]. AB - We performed selective pulmonary arterial occlusion test (SPAO) and unilateral pulmonary arterial occlusion test (UPAO) in 30 patients with lung cancer who would be undertaken right lower lobectomy or middle and lower lobectomy, and evaluated the preoperative cardio-pulmonary function. The lung hemodynamics during SPAO were different from those during UPAO. This indicates that SPAO evaluated reserve capacity of vascular bed in the right upper lobe which would be remained at the surgery. Moreover, the ratio of total pulmonary vascular resistance during SPAO to that of before SPAO was not differed in two groups, one was a group with and the other was a group without impaired reserve capacity of vascular bed in the contralateral lung. This suggests that reserve capacity of pulmonary vascular bed including right upper lobe would be well compensated even in the patients with highly impaired capacity in the contralateral lung. Based on these findings, we performed lung resections in 9 patients, who were judged contraindications for lung resection by the results of UPAO, and no patient suffered postoperative cardio-pulmonary complications. Total pulmonary vascular resistance immediately after the right middle and lower lobectomy were equal to those during SPAO. Thus we conclude that SPAO is very useful technique for evaluating cardiopulmonary function after right lower lobectomy or middle and lower lobectomy, and that it would be possible to extend the boundaries of safety for lung resection based on evaluation of cardio-pulmonary function by SPAO. PMID- 1940517 TI - [Clinical study of centrifugal pump bypass as an auxiliary technique for surgical treatment of descending thoracic aorta]. AB - Left heart bypass or arterial bypass using a centrifugal pump (Bio-pump bypass) with a H-PSD shunt tube was performed as an auxiliary technique for the treatment of descending thoracic aorta in 13 cases. Hemodynamic differences during aortic clamp were compared between cases using Bio-pump bypass and 4 cases of axillo femoral temporary bypass which were carried out in the first term. Furthermore, in Bio-pump bypass cases, the bypass route was investigated from the point of view of operative complications in relation to bypass technique. Peripheral blood pressure and urinary output during aortic clamp were significantly increased in the Bio-pump bypass group. Those results indicated that the Bio-pump bypass was useful as an auxiliary technique especially for high risk patients with low renal function. In particular, left heart bypass was a beneficial technique which was not affected by modality or region of disorder in the descending thoracic aorta. However, this technique should be selected carefully for patients with cardiac disease, for instance severe left ventricular hypertrophy, because two cases of operative complications consisting of pericardial effusion related to the bypass technique were experienced in this study. PMID- 1940518 TI - [Cardiac function during exercise in patients with coronary bypass surgery assessed by continuous ventricular function monitoring]. AB - The response of left ventricular function during exercise and recovery after exercise was assessed in 52 patients with coronary artery bypass surgery by means of a radionuclide continuous ventricular function monitor. This system consists of 2 radionuclide detectors, recorder and a computer. After the equilibration of 20 mCi technetium 99m-labeled autologaous red blood cells into the intravascular space, the beat by beat radionuclide data were summed for 20-sec intervals to measure left ventricular ejection fraction (EF). Before surgery, the mean EF decreased with exercise from 51 +/- 9% to 45 +/- 11% (p less than 0.001). Cardiac response was divided into 4 types according to the profiles of the EFs during exercise. In 6 patients, EF continued to increase until maximal exercise (type A). In 10 patients, EF initially increased and then decreased in late exercise stages (type B). In 9 patients, EF did not change significantly during exercise (type C). In 27 patients, EF decreased throughout exercise (type D). After surgery, the mean EF increased with exercise from 53 +/- 10% to 60 +/- 13% (p less than 0.001). Thirty-five patients showed type A, 9 type B, 5 type C, and 3 type D. Two type D and 5 type B patients had occluded grafts or ungrafted coronary arteries. Four patients with complete revascularization including an internal thoracic artery and saphenous vein grafts showed type B. Three patients with extensive infarction and poor left ventricular function showed type C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940519 TI - [Prediction of postoperative exercise capacity in lung resection candidates]. AB - The relation between submaximal oxygen consumption (MVO2) before and after lung resection was studied, and the possibility to predict postoperative MVO2 was investigated. Thirty four patients (19 lobectomies, 9 bi-lobectomies, 6 pneumonectomies) performed exercise tests one week before operation and at the time when they were able to resume work daily after operation (in two to eleven months). Predicted postoperative MVO2 was calculated from preoperative MVO2 as follows: 0.8 x resection rate x age index x preoperative MVO2 + 183. In this formula the resection rate means [the number of total lung segments--the number of non-working segments]. The age index is 1.5 for patients under 50 years, 1.0 for those between 50 to 69, and 0.8 for those over 70. This predicted MVO2 had strong correlation with actual postoperative MVO2 (r = 0.94, t = 13.4, y = 1.08x 83) in twenty five patients. Correlation was low in the remaining nine patients, however. The nine had old myocard infarction, postoperative cerebral infarction, marked wet lung, anticancerous chemotherapy within ten days or marked reduced exercise capacity (below 3 METS at maximal exercise). From these results, we concluded it is possible to predict the postoperative MVO2 using preoperative MVO2 except in cases which have some exercise limiting factors or whose exercise capacity is very small. PMID- 1940520 TI - [Pulmonary thromboembolectomy of subacute massive pulmonary thromboembolism in a patient with familial antithrombin III deficiency]. AB - Reported is a case of successful pulmonary thromboembolectomy and inferior caval vein interruption in a patient with subacute massive pulmonary thromboembolism (PTE). He had been complicated by the right atrial and deep vein thrombosis due to type I familial antithrombin III (ATIII) deficiency. Pulmonary embolectomy and caval interruption was performed 20 days after the initial attack and followed by anti-coagulation therapy. Thrombi weighed 50 gm were removed mainly from the left pulmonary artery. The right atrial thrombus which had got smaller by the preoperative fibrinolytic therapy could not be found with right atriotomy. Respiratory function at rest and slightly elevated pulmonary arterial pressure was normalized post-operatively. Although the PTE in this patient was considered to be subacute by the histological findings of the fibrin thrombus removed, tapering of pulmonary arteries in PAG and obstructive intimal hypertrophy of the small vessels in the lungs suggests the chronic nature of the PTE (post thrombotic obstruction of pulmonary arteries) caused by the hyper-coagulable state. In patients with familial ATIII deficiency, 50% of normal ATIII activity can be expected because they are heterozygotes, so the cardio-pulmonary bypass should be run with special caution to the heparin dosage. Caval vein interruption and warfarin therapy are recommended for prophylaxis of recurrent PTE. PMID- 1940521 TI - [Left atrial myxoma in a 16-year-old girl following acute myocardial infarction- a case report and a review of 17 cases in the world]. AB - A 16-year-old girl had clinical signs of an acute myocardial infarction. Echocardiography revealed left atrial myxoma and coronary angiography demonstrated a complete obstructive lesion at LAD. Coronary arterial embolization from myxoma was strongly suggested. The tumor was removed successfully 32 days after acute coronary embolization. Coronary embolization from left atrial myxoma is extremely rare. There are only 17 reports in the world and we reviewed these reports. PMID- 1940522 TI - [Mitral and aortic valve replacement with tricuspid annuloplasty in a patient suffering from hereditary spherocytosis]. AB - A 51-year-old woman was admitted with increasing shortness of breath. Preoperative evaluation disclosed MSr + ASr + TR. She had been undergone a splenectomy at 35-year-old for hereditary spherocytosis (HS). The patient underwent successful mitral valve replacement with a No. 25 Bjork-Shiley (BS) valve, aortic valve replacement with a No. 21 BS valve, and tricuspid valve annuloplasty by means of membrane oxygenator (COBE). Haptoglobin and poloxamer 188 were used for prevention of hemolysis during extracorporeal circulation. No significant hemolysis occurred intra-or postoperatively. A very rare case of open heart surgery associated with HS was reported. PMID- 1940523 TI - [Complete resection of thymic carcinoma supported by cardiopulmonary bypass]. AB - We would like to report on a case of thymic carcinoma that could be completely resected supported by extracorporeal circulation. A 53-year-old female complaining of severe coughing and hoarseness was admitted to our hospital. Her chest X-ray film revealed an abnormal shadow in the upper mediastinum and an elevation of the left diaphragm. Chest CT and MRI showed an anterior mediastinal mass that invaded the main pulmonary artery. The preoperative histological diagnosis of thymoma was made by mediastinoscopic specimen. After 50 Gy irradiation, surgery was performed. During the operation, after resection of the left brachiocephalic vein and a part of the upper lobe of the left lung, the tumor was detached from the wall of the aorta and resected with the invaded part of the pulmonary artery supported by cardiopulmonary bypass. Reconstruction of the pulmonary wall defect was accomplished with Xenomedica. The final pathological diagnosis was thymic adenosquamous carcinoma. The postoperative course has been uneventful 24 months after surgery. Extracorporeal circulation is a useful technique in operations involving malignant diseases when complete resection is able to be accomplished. PMID- 1940524 TI - [Cervical and mediastinal node dissection four and a half years after operation for pulmonary adenocarcinoma]. AB - Metastasis to bilateral mediastinal and cervical lymphnodes was noted in a 58 year old male four and a half years after left lower lobectomy of the lung with lymphnode dissection (R2a, P-T1N2M0) by posterolateral incision. This case was treated by dissection of the left cervical and bilateral mediastinal lymphnodes from left cervical and median sternal incisions. Metastasis to the right supraclavicular lymphnodes was noted 11 days after discharge, and additional right cervical dissection was performed with satisfactory results. These possible routes include the tracheobronchial lymphnodes and the carinal nodes, via the upper or anterior portion of the left main bronchus. The routes continue via the nodes surrounding the trachea and the right paratrachea to the cervical nodes. This case suggests the necessity of bilateral mediastinal dissection and the significance of cervical dissection in left lung cancer. PMID- 1940525 TI - [Surgical repair of Scimitar syndrome with azygos connection by extracardiac conduit between right pulmonary vein and left atrium]. AB - We present a surgical case of 41-year-old woman with Scimitar syndrome. Preoperative catheterization showed azygos connection and L-R shunt ratio of 45% without intracardiac malformations. To our knowledge, this combination has not been previously reported. At operation the right single pulmonary vein was found and drained into the inferior vena cava below the diaphragm. Because of counter clockwise rotation of the heart the distance of the scimitar vein and the left atrium was too long for direct anastomosis, a polytetrafluoroethylene tube (10 mm in diameter) was utilized for an extracardiac conduit using cardiopulmonary bypass. Postoperative course was uneventful. We conclude that this technique is effective for this syndrome with a large amount of L-R shunt and a sufficient patency is expected. PMID- 1940526 TI - [Chronic hemorrhagic empyema developed in thirty three years after the right pneumonectomy--a case report]. AB - A 55-year-old man was admitted because of exertional dyspnea. He had the right pneumonectomy thirty three years ago. Chest X-ray showed the mediastinal shift to the left. And chest CT scan showed right intrathoracic mass. The bloody pleural effusion was aspirated (Hb 9.4 g/dl) and its examination revealed Staphylococcus epidermidis. We resected the empyema cavity. During the operation, massive bleeding was experienced (total 23200 ml). Pathologically, micro blood vessels were marked in the organized hematomas and the pleura. Chronic hemorrhagic empyema is a specific type of chronic empyemas and it is dangerous to remove of the hematomas because of massive bleeding. PMID- 1940527 TI - [Successful repair of subvalvular annular aneurysm of the left ventricle]. AB - A 62-year-old woman was admitted to our hospital due to congestive heart failure. On the chest X-ray film, cardiomegaly and prominent pulmonary congestion were revealed. She became well with bed rest and medication of digitalis and diuretics. Echocardiogram established the diagnosis of severe mitral regurgitation. In addition, cineangiography of the left ventricule showed cystic left ventricular aneurysm which originated from below the posterior mitral annulus. Operation was performed on July 16, 1990. Under cardiopulmonary bypass, we reflected the apex of the LV upwards, but failed to identify the aneurysm. Then, left atrium was opened through Dubost incision. As regards mitral valve structures, there were no abnormal findings except moderate enlargement of it's orifice. After resection of the mitral valve, orifice of the aneurysm (0.5 X 2.0 cm) was recognized, which was closed with the buttressed sutures. Afterwards, MVR was performed with 25 mm Medtronic Hall valve. The patient had a smooth postoperative course without complication. PMID- 1940528 TI - [A surgically treated case with lung cancer on maintenance hemodialysis]. AB - Maintenance hemodialysis for chronic renal failure has spread all over the country, and the number of patients in whom surgical indications are considered to concomitant diseases has been increasing. A 76-year-old male was admitted due to lung cancer on maintenance hemodialysis. The chest roentgenogram showed a 2.5 cm sized coin lesion in the right middle lung field. Preoperative examinations, chest tomography, chest CT-scanning, bone scintigraphy, bronchofiberscopic biopsy, etc. led to a diagnosis of primary lung cancer (squamous cell carcinoma). Hemodialysis with prescribing nafamostat mesilate (40 mg/hour) was performed the day before the operation and on the first, fourth and sixth postoperative days. There was no postoperative bleeding. The patient has been well for 27 months postoperatively. PMID- 1940529 TI - [Occlusion of the right pulmonary artery due to acute dissecting aortic aneurysm]. AB - A 58-year-old female was admitted with an abrupt onset of chest and back pain. The CT scan of the chest showed aortic dissection of the ascending aorta and proximal aortic arch, but the false lumen of the aortic dissection had already been occluded by a blood clot. After admission, she complained of chest pain with hemoptysis and presented facial edema and the distention of the neck veins. The pulmonary angiogram showed complete occlusion of the right pulmonary artery at the proximal segment. These findings were interpreted as pulmonary embolism. She was treated with intravenous heparin and urokinase, but these treatments did not demonstrate any improvement. She underwent a surgical exploration on the fourth hospital day. During surgery, the right pulmonary artery was discovered to be compressed and occluded by the large dissecting aneurysm of the ascending aorta. In addition, hematoma was seen between the right pulmonary artery. The ascending aorta and pulmonary trunk, which was injured in the operative procedure, were replaced with an artificial graft successfully. Postoperative pulmonary angiogram showed no stenosis of right pulmonary artery. The occlusion of the pulmonary artery by an acute dissecting aneurysm is an extremely rare complication and it is often wrongly diagnosed as pulmonary embolism. In such cases, the correct diagnosis and prompt surgical treatment is essential and antithrombolytic and anticoagulant therapy should be avoided. PMID- 1940530 TI - [A case of pulmonary coccidioidomycosis]. AB - A 55-year-old Japanese woman was admitted to our hospital, complaining of flu like symptoms and left-sided chest pain. Her chest X-ray films revealed a solitary coin lesion in the left middle lung field. She had traveled to California and Arizona 3 months before being taken ill. Because of negative result in sputum cytology and trans-bronchial lung biopsy examination, open lung biopsy and wedge resection was performed. Histological examination revealed endosporulating spherules in a caseous lesion of the epithelioid granulomas, and fungal cultures demonstrated barrel-shaped arthropores. Pulmonary coccidioidomycosis was diagnosed. Coccidioidomycosis is a rare fungal disease found in certain endemic areas in the southwestern region of the United States. She had been infected during her travels in America, and this is the second case in Japan who had taken surgical intervention for pulmonary coccidioidomycosis. PMID- 1940531 TI - [A case report of entrapment of PTCA balloon catheter caused by its rupture]. AB - This is a report of a rare case in which an angioplasty balloon catheter became entrapped within the lumen of the coronary artery after the balloon ruptured during percutaneous transluminal coronary angioplasty (PTCA). The patient was a 69-year-old man who underwent elective PTCA of the circumflex coronary artery (Cx) with USCI 2.5 mm new Probe. The inflation failed to dilate the lesion up to 18 bar; at this pressure, balloon rupture was observed. Any attempt to withdraw the balloon catheter across the lesion was not successful, and then the patient was transferred to the operating room for removal of the balloon catheter. After establishing cardiopulmonary bypass, an arteriotomy in the Cx confirmed that the balloon fragment had become entrapped at a sharp edge of calcific stenosis after balloon rupture. The entrapped catheter was successfully removed from the arteriotomy of the Cx, and coronary bypass grafting was performed to the left anterior descending artery which had restenosis after PTCA 3 months ago. The patient had an uneventful postoperative course and was discharged in excellent condition 30 days after surgery. The balloon rupture of PTCA had been considered a minor problem, however, as this case demonstrated, this seemingly benign complication may lead to potentially disastrous consequences. PMID- 1940532 TI - [Coronary artery bypass grafting using the right gastroepiploic artery--an experience of simultaneous operation]. AB - Coronary artery bypass grafting using the right gastroepiploic artery and cholecystectomy were simultaneously performed on a 62-year-old woman with both angina pectoris and cholecystolithiasis, with good results being obtained. No case of combined surgery with such coronary bypass has been reported yet. The present simultaneous surgery from our recent experience was regarded as a very useful surgical approach because of only one possible risk of surgical complications such as anesthetic accident, infection, etc, and of easy availability of the right gastroepiploic artery at laparotomy for coronary artery bypass grafting requiring some arterial graft. PMID- 1940533 TI - [A case report: coronary artery bypass grafting for the patient with essential thrombocythemia]. AB - A 53-year-old man was suffered from progressive effort angina. Coronary angiogram revealed complete obstruction of the left anterior descending artery with collaterals from posterior descending artery. The essential thrombocythemia was diagnosed from platelet count over 1,000,000/mm3 with bleeding tendency. And hyperlipidemia was not observed. After the platelet count was reduced into normal range by administration of Melphalan, coronary artery bypass grafting using the left internal thoracic artery was performed successfully. The main cause of his coronary artery disease was thought to be secondary to the essential thrombocythemia as his past history included cerebral infarction secondary to transient thrombus formation in the common carotid artery which was confirmed with cerebral angiography. He has been on melphalan, warfarin and dipyridamol therapy after the operation without chest symptom. PMID- 1940534 TI - [A case report on the perforation of a gastric tube ulcer after esophageal reconstruction for cancer]. AB - The development of peptic ulcers in gastric tubes used for esophageal reconstruction for cancer are rare. However, they can potentially cause serious complications, including perforation and hemorrhaging. We experienced a case in which an ulcer of large size developed in the gastric tube, and it was very difficult to treat. The patient was a 72-year-old man, who had undergone an esophagotomy of the thoracic portion, an gastroesophagoplasty through the anterior portion of the sternum, and postoperative radiotherapy 2 years ago. Eight days after his admission, the ulcer began excessive bleeding, and we performed an emergency operation. The ulcer perforated into the mediastinum, and developed an abscess involving the intrathoracic artery. After hemostasis and debridement, we resected the upper half of the gastric tube, closed the oral side of the remaining portion, and converted the cervical esophageal stump into an external fistula. The wound was covered with a flap. A histological examination showed an ulcer with no evidence of malignancy, and without any signs of healing. Five months were required for the wound to heal completely. After that, we succeeded in reconstruction through jejunal free-transfer, using the microvascular surgery technique. Some pathogenesis is suggested for gastric ulcers after gastroesophagoplasty. Despite performing a vagotomy, the secretion of acid from the gastric mucosa is common. Both this condition, and the deterioration of the mucosal barrier caused by surgery, can play significant roles in the development of the ulcer. The histological influence of postoperative radiotherapy is also important, as this treatment aggravates the circulatory disturbance, and disturbs the histological reaction necessary for healing. PMID- 1940535 TI - [Angiosarcoma of the chest wall with chronic empyema--a case report]. AB - A 65-year-old man admitted to our hospital with a complaint of painful tumor of chest wall. By preoperative aspiration cytology and biopsy, the tumor was diagnosed as a sort of sarcoma. Tumor, empyema cavity and lower lobe of the right lung was resected en bloc. Pathological diagnosis was angiosarcoma originated from the chest wall with chronic empyema. Chest wall angiosarcoma is a rare disease, and its prognosis is grave. One of the causes of chest wall sarcoma with chronic empyema is considered to be repeated chronic inflammation. PMID- 1940536 TI - Lag screw versus position screw techniques for rigid internal fixation of sagittal osteotomies: a comparison of stability. AB - Both lag screw and position screw techniques have potential advantages and disadvantages when used for securing sagittal osteotomies of the mandible. This study evaluated 56 patients undergoing bilateral sagittal split osteotomies for mandibular advancements. Osteotomies were fixed with either a position screw or lag screw technique using 2-mm self-threading screws. Five cephalometric points and two angles were used to evaluate skeletal changes. There were no statistically significant differences in the postsurgical movement of point B or the mandibular incisor. There were slight statistically significant differences in the horizontal and vertical movements of gonion. Overall, similar postoperative stability existed in both groups. Gonion and gonial angle changes were detected cephalometrically but had no effect on the clinical outcome. PMID- 1940537 TI - Longitudinal study of combined orthodontic and surgical treatment of Class II malocclusion with deep overbite. AB - Twenty-one patients who had undergone orthodontic treatment in combination with mandibular advancement surgery to treat Class II malocclusion and deep overbite were followed up. Median vertical relapse at the bony chin (after a mean followup of 16 months) was found to be 2.9 mm (44%). Sagittal advancement was found to have good stability; most of the patients exhibited some additional anterior movement of the chin during the follow-up period. At the same time, the entire mandible rotated counterclockwise and the gonial angle increased. Individual response to treatment varied greatly; two patients exhibited major horizontal relapse. Controlling the position of the mandibular proximal segment seemed to be the most important factor in posttreatment stability of this sample. PMID- 1940538 TI - Effects of interdental osteotomies on the periodontal and osseous supporting tissues. AB - The effects of 40 interdental osteotomies on surrounding osseous and periodontal structures were evaluated clinically and radiographically. No statistically significant changes were noted in any of the clinical parameters except gingival height, which decreased slightly in the maxilla and increased in the mandible. These changes were found to be statistically significant, but not clinically significant, and are most likely explained by the direction of movement of the bony segment. Radiographic evaluations revealed no statistically significant changes other than an increase in interdental width in both the maxillary and mandibular sites. These measurements were made at the root level, and, although the crowns were moved closer, the roots may actually have flared apart because the anterior segment was tipped to upright the incisors. The lack of change in the other radiographic parameters indicated that there was no loss of alveolar bone support. PMID- 1940540 TI - Laboratory evaluation of surgical ball hook crimping pliers. AB - Newly introduced crimping pliers for use with surgical ball hooks were laboratory tested against the previous design, because in the past hooks have been lost during the surgical procedure. The new pliers demonstrated an improved "friction lock" over the old design. However, it is still recommended that a continuous ligature be used with the final surgical arch wire to avoid the possibility of displacing hooks laterally off the arch wire during surgical and postsurgical procedures. PMID- 1940539 TI - Condylar hyperplasia: remodeling of facial structures following condylectomy. Report of two cases. AB - Condylectomy accompanied by either simultaneous or postponed surgical correction of facial asymmetry is the treatment of choice in cases of condylar hyperplasia in its active stage. However, spontaneous remodeling processes in facial structures following the elimination of an actively growing hyperplastic condyle may bring about improvement in symmetry without further surgical intervention. Two cases are presented. PMID- 1940541 TI - Stability after surgical-orthodontic correction of skeletal Class III malocclusion. I. Mandibular setback. AB - Postsurgical stability of mandibular setback to correct mandibular prognathism was compared for three approaches: transoral vertical ramus osteotomy, bilateral sagittal split osteotomy with wire osteosynthesis and maxillomandibular fixation, and bilateral sagittal split osteotomy with rigid internal fixation via bone screws. In the transoral vertical ramus osteotomy group, the mean postsurgical change in chin position was almost zero, but nearly 50% of the patients did have clinically significant changes in chin position; two thirds of these movements were posterior and one third anterior. In the bilateral sagittal split osteotomy groups, the chin either stayed in its immediately postsurgical position or moved anteriorly. In one fourth of the patients who received maxillomandibular fixation and in nearly half of the patients who received rigid internal fixation, the chin moved forward more than 4 mm. PMID- 1940542 TI - [Cellular localization of aromatase in human endometrium]. AB - The expression of aromatase was examined in human endometrium throughout the menstrual cycle, early pregnancy, and ovarian endometriosis with a specific monoclonal antiserum to human purified placental aromatase cytochrome P-450 (P 450AROM). Tissues were obtained from women undergoing hysterectomy, oophorectomy and/or intrauterine curettage. The day of the cycle was determined from the onset of the last menstrual period and confirmed by endometrial histology. In secretory endometrium, stronger immunoreactivity of aromatase was observed in epithelial gland than immunoreactivity of stroma, especially in mid and late secretory endometrium. In endometrium of early pregnancy, significant immunoreactivity was seen in both glandular cells and stromal cells. However, weak immunoreactivity was seen only in epithelial gland of ovarian endometriosis. There was no immunoreactivity in atrophic endometrium or late proliferative endometrium. These results show that the physiological action of endometrial aromatase is modulated by progesterone and equipped with the capacity for cyclic change throughout the menstrual cycle. The presence of aromatase in the ovarian endometriosis is of interest, since it is histologically different from normal cyclic endometrium, and this is consistent with the ability to synthesize estradiol. But the weak intensity in endometriosis probably means that only a small amount of estradiol was synthesized, which served to explain the poor response to GnRHa or danazol administered on ovarian cystic endometriosis. PMID- 1940543 TI - [In vitro studies on the expression of c-myc oncogene product in gynecological cultured cancer cells]. AB - In this study, immunocytochemical and biochemical detection of c-myc protein in gynecological cultured cancer cells were performed together with gene expression of the cells. OMC-1 (cervical squamous carcinoma cell line), OMC-2 (endometrial adenocarcinoma cell line), OMC-3 (ovarian mucinous adenocarcinoma cell line) and OMC-4 (cervical adenocarcinoma cell line) were used. Immunocytochemically, c-myc protein was detected in both nuclei and cytoplasms of cultured cells when they were fixed in 95% ethanol, 10% formalin and 4% paraformaldehyde (PFA) including 10mM NaCl. However, it was detected in the nuclei of almost all of the cells in nuclei of the cells when they were fixed in 4% PFA including 1,000mM NaCl. Western blotting against a nuclear fraction of the cells demonstrated 66Kd protein in OMC-1 and 62Kd protein in OMC-2,3,4, respectively. They were completely absorbed by c-myc synthetic peptide. However, there was no reaction against the cytoplasmic fraction of the cells. Slot blot hybridization against the DNA of the cells demonstrated 15 times and 5 times c-myc gene amplification in OMC-2 and OMC-4, respectively. These results suggest that OMC-1,2,3,4 can be used as positive controls for the immunocyto- and histochemical detection of c myc protein in clinical materials. However, it must be noted that the redistribution of c-myc nuclear protein into the cytoplasm may occur in the fixation process. PMID- 1940545 TI - [Evaluation of the diagnostic criteria of gestational diabetes mellitus in Japan: a study of women with mild glucose intolerance during late pregnancy]. AB - To evaluate the validity of the diagnostic criteria of gestational diabetes (GDM) recommended by the Japan Society of Obstetrics and Gynecology (JSOG), we investigated women with mild glucose intolerance during pregnancy, using the borderline criteria of the Japan Diabetes Society (JDS), cut-off values of which are lower than those of the JSOG criteria. Five hundred seventy one pregnant women were screened for GDM after 20 weeks' gestation using a 50g glucose challenge test. Only ten women (1.8% of total), who fulfilled the JSOG criteria, were found (GDM group). At the same time, eighteen women (3.2% of total), who did not fulfill the JSOG criteria but who met two or more abnormal values of the JDS borderline criteria, were also found (A2 group). There was no significant difference between the two groups in either mean maternal age or the percentage of women over 30 years of age. delta IRI/delta BS in a 75g glucose tolerance test in the A2 group was 0.58 (median), which was similar to that in the GDM group (0.42). This result, however, was significantly lower than that in both the normal control group (1.00, p less than 0.01) and the group of women with only one abnormal value among the JDS criteria (A1 group, 0.88, less than 0.01). Before therapy, there was no significant difference in the diurnal plasma glucose level between the GDM group, who could be treated with diet therapy, and the A2 group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940544 TI - [An analysis of factors associated with ectopic pregnancy following in vitro fertilization and embryo transfer]. AB - Five ectopic pregnancies occurred in 75 in vitro fertilization and embryo transfer (IVF-ET) pregnancies (6.7%) in Ogikubo Hospital IVF program between 1985 and 1989. The indication for IVF in 70 pregnancies was a tubal factor. Thirty cases were among 70 pregnancies with hydrosalpinx, and 40 cases were with other tubal conditions. All of the five cases had tubal disease. Four of them had hydrosalpingos. The percentage of ectopic pregnancies for the 30 pregnancies with hydrosalpinx was 13.3%, while for 40 pregnancies with other tubal conditions it was 2.5%. However, there was no significant difference between the two groups. No correlation was found in other parameters including superovulatory methods, oocyte recovery procedure, number of embryos transferred, embryo transfer procedure, and endocrine changes after embryo transfer. In this study, we were unable to identify a difference between ectopic pregnancy and intra-uterine gestation in IVF-ET. However, further study is required to clarify whether hydrosalpinx increases the risk of ectopic pregnancy in IVF-ET. PMID- 1940546 TI - [Effect of maternal postural change on maternal hemodynamics in late pregnancy- supine hypertension]. AB - The purpose of this investigation was to ascertain the effect of postural change in late pregnant women from the left lateral recumbent position to the supine position on their blood circulation. Patients in whom the blood pressure at the right upper limb in the supine position increased by at least 20mmHg or more (diastolic and/or systolic pressure) were classified as the supine hypertensive group. Patients in whom the blood pressure of the right upper limb decreased by at least 20mmHg or more were classified as the supine hypotensive group. And other patients were classified as the no blood pressure change group. The results were as follows. 1. The incidence of supine hypertension was 48% in primigravidas and 38% in multigravidas. Supine hypertension was especially common in PIH (pregnancy induced hypertension) complicated women (75%). 2. Maternal cardiac function: With postural change from the left lateral recumbent position to the supine position, CO (cardiac output) decreased and SVR (systemic vascular resistance) was increased in both the supine hypertensive and the no blood pressure change groups by the thermodilution method (n = 14). CVP (central venous pressure) and PCWP (pulmonary capillary wedge pressure) shows different pattern of change in the supine hypertensive group and the no blood pressure change group. In the former group, CVP was decreased by 45 +/- 16% and PCWP was increased by 21 +/- 9% in the supine position compared with in the left lateral recumbent position. However, in the latter group, CVP decreased by 87 +/- 69% and PCWP decreased by 53 +/- 46% as the result of the same postural change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940547 TI - [The effects of insulin-like growth factor-I (IGF-I) and IGF-II on prolactin (PRL) release from human decidua and amniotic fluid circulation]. AB - It has been reported that insulin-like growth factor (IGF) may play an important role in the feto-placental environment during pregnancy. The present study was undertaken to investigate the effect of IGF-I and IGF-II on prolactin (PRL) release from human decidual cells in vitro and in vivo. The human decidua in early pregnancy was obtained by D & C, and was enzymatically dispersed into a monocellular suspension. Monolayer cultures of these cells were exposed for 96 hours to either control media or medium supplemented with IGF-I and IGF-II. PRL levels in the media were measured by EIA. Five days after dispersion, the intracellular calcium concentration [( Ca]2+i) in cultured decidual cells was measured by the Fura-2 fluorescence method with a Spectrofluorometer. PRL and IGF I levels in amniotic fluid of 2nd trimester and term pregnancy were measured by RIA for in vivo study. In an in vitro study, IGF-I increased PRL release from decidual cells significantly during a 96 hour culture. However, IGF-II did not enhance this PRL release. IGF-I stimulation had no effect on [Ca]2+i. In an in vivo study, amniotic fluid IGF-I levels in the 2nd trimester (139.8 +/- 28.1 ng/ml) were significantly higher than those in term pregnancy (46.4 +/- 14.2 ng/ml), and a significant positive correlation (r = 0.852, p less than 0.001) was observed between IGF-I and PRL levels in the amniotic fluid. The present in vivo and in vitro studies indicated that IGF-I plays an important role in PRL release from decidua into amniotic fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940548 TI - [Prenatal evaluation of the platelet counts in the fetuses and the neonates of the mothers complicated with idiopathic thrombocytopenic purpura]. AB - We investigated 25 pregnancies with ITP. The results were as follows. 1. The platelet counts of the maternal blood just before delivery were not correlated with those of the cord blood. 2. It was suggested that the maternal PAIgG value just before delivery could foretell the onset of neonatal thrombocytopenic purpura. 3. The platelet counts in fetal scalp blood were correlated with those of the cord blood, but falsely lower platelet counts were found in the fetal scalp samples. 4. We saw 5 cases of percutaneous umbilical blood sampling (PUBS) in pregnancies with ITP. PUBS was found to be a useful and safe method. The indications for PUBS and fetal platelet transfusion in pregnancy with ITP are discussed. PMID- 1940550 TI - [Modification of endocrine function of trophoblasts by thyroid hormone]. AB - Direct effects of L-triiodothyronine(T3) on placental endocrine function were investigated in vitro with an organ culture system for human placental tissues. Explants of trophoblastic tissues obtained from early and term placentas were cultured with or without graded doses of T3 in a serum-free condition. The addition of an optimal concentration of T3(10(-3) M T3) stimulated daily secretion of progesterone and estradiol from cultured early placental tissues by acting at the level of 3 beta-hydroxysteroid dehydrogenase and aromatase enzyme activity, together with the enhancement of hCG(alpha, beta) and hPL secretion. The addition of higher or lower concentrations of T3 gave attenuated effects and the addition of an excessive concentration of T3(10(-3) M T3) resulted in remarkable inhibition of progesterone and estradiol secretion by cultured early placental tissues. These results suggest that the optimal concentration of thyroid hormone acts as a biological amplifier of endocrine function of cultured trophoblasts obtained from early placentas. Unlike the early placental tissues, cultured term placental tissues did not respond to the addition of graded doses of T3 with increased endocrine function. Thus, the frequent occurrence of spontaneous abortion in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of the trophoblast, followed by diminished endocrine function of early placental trophoblasts. PMID- 1940549 TI - [Effects of various growth factors on the proliferation and the differentiation of trophoblastic cells in vitro]. AB - EGF, PDGF, IL-6, TGF-beta 1 and supernatants from decidual cell cultures were added in various concentrations to cultures of normal trophoblastic cells in vitro. Effects on cell proliferation and differentiation were assessed by using 3H-thymidine uptake test and measuring hPL, hCG production in culture media, respectively. EGF stimulated only hPL, hCG production and in contrast, PDGF stimulated 3H-thymidine uptake only. IL-6, TGF-beta 1 and decidual supernatants stimulated both hPL, hCG production and 3H-thymidine uptake, especially TGF-beta 1 and decidual supernatants. These results suggest that EGF is related to the differentiation, PDGF is to the proliferation, and IL-6, TGF-beta 1 and decidual supernatants are to both the differentiation and proliferation of trophoblastic cells. Further understanding of the effects of these products on trophoblastic growth may provide important insights into mechanisms of early pregnancy development. PMID- 1940551 TI - [Clinico-statistical study on pyometra in high-aged outpatients]. AB - We clinico-statistically studied outpatients with pyometra aged 60 or older who visited our outpatient clinic during the past four years. 1. Pyometra was diagnosed in 48 cases (13.6%) of 353 in which the uterine cavity could be examined. The incidence became significantly higher with age (p less than 0.01). 2. Thirty-two patients with pyometra were found to require a wheelchair or to be in an immobilized state (bedridden). These patients with poor activity in daily living amounted to 76.2% of 42 cases which were not a complication of malignant uterine tumor or tuberculous endometritis. 3. Pyometra was diagnosed in 29 patients of 96 with urinary and/or rectal incontinence (30.2%). This incidence was significantly higher than that in our patients without incontinence (5.5%) (p less than 0.01). 4. Hematological and blood chemistry study revealed abnormality of the peripheral leucocyte count in 34.5% and CRP abnormality in 70.4% of all the cases of pyometra. 5. Mixed infection by both aerobic and anaerobic bacteria was observed in 16 cases of 36 in which strain could be determined by pus culture. Streptococcus sp. and Bacteroides sp. were predominant as aerobic and anaerobic bacteria, respectively. The present study on pyometra cases of aged people demonstrated that poor activity in daily living and incontinence were significant factors causing this disease. It also revealed the various features of pyometra in aged people. PMID- 1940552 TI - [Ultrastructural abnormalities of spermatozoa in infertile male patients and their implications in fertilizing capacity in vitro]. AB - The purpose of this study was to clarify the relation between ultrastructural abnormalities of spermatozoa and the fertilizing capacity of the spermatozoa in vitro. The infertile male patients who underwent in vitro fertilization were divided into two groups: the no fertilization group (NFG, n = 20) and the fertilization group (FG, n = 18). Morphological features of the spermatozoa in the two groups were studied by transmission electron microscopy (TEM). 1) The percentage of normal heads in the FG was significantly higher than that in the NFG (27.9 +/- 15.4% vs 9.6 +/- 13.3%, p less than 0.001). The percentage of abnormal acrosomes (62.3 +/- 16.4% vs 78.9 +/- 17.6%, p less than 0.01) and nuclear defect of spermatozoa (14.5 +/- 7.2% vs 24.9 +/- 13.3%, p less than 0.01) in the FG was significantly lower than that in the NFG. 2) The percentage of normal tails in the FG was significantly higher than that in the NFG (64.9 +/- 20.2% vs 47.7 +/- 18.9%, p less than 0.05). The percentage of deleted peripheral microtubules was significantly lower in the FG (9.3 +/- 5.9% vs 15.8 +/- 9.4%, p less than 0.02). 3) Three effective variables, normal heads, deleted peripheral microtubules, and nuclear defects, were selected by the forward selection method to discriminate the two groups. The discriminant analysis by means of these three variables showed that apparent accuracy was 84%. The present study demonstrated that the ultrastructural analysis by TEM makes it possible to show more precisely the abnormalities of acrosomes and tails of spermatozoa. This may be useful in evaluating the fertilizing capacity of spermatozoa in male infertility. PMID- 1940553 TI - [Evaluation of the renal artery in the fetuses with growth retardation and oligohydramnios by two dimensional Doppler ultrasonography]. AB - Renal blood flow dynamics were studied with color and pulsed Doppler ultrasound in 102 normal fetuses at 20 to 40 weeks of gestation, 11 growth retarded fetuses (group A), 15 fetuses with oligohydramnios (group B) and 10 growth retarded and oligohydramniotic fetuses (group C) at 32-40 weeks of gestation. The maximum systolic velocity (VMAX), early diastolic peak velocity (VEA), end diastolic velocity (VED) and resistance index (RIEA:VMAX-VEA/VMAX and RIED:VMAX-VED/VMAX) were measured in the renal artery. VMAX was also measured in the ascending aorta (AO) and pulmonary artery (PA). In the normal fetuses, blood flow velocity increased with gestational age, but VMAX and VEA remained constant after 28 weeks of gestation. The resistance index decreased with gestational age, but RIEA remained constant after 28 weeks of gestation. RIED in groups A and C increased significantly, and VMAX in groups B and C, and VED in group C decreased significantly compared with normal fetuses. VMAX in AO and PA decreased remarkably in the three abnormal groups. It was concluded that the kidneys were poorly perfused in the growth retarded fetuses with oligohydramnios, which may, in part, depend on the decreased stroke volume. PMID- 1940554 TI - [Fetal heart rate patterns in response to acoustic stimulation]. AB - Fetal heart rate response to fetal acoustic stimulation (FAST) during the antepartum period after 25 weeks of gestational age was studied in 157 cases of normal pregnancy, 22 cases of fetal distress, 12 cases of SFD, 10 cases of fetal malformation, 9 cases of placental dysfunction, 4 cases of oligohydramnios, 12 cases of toxemia of pregnancy, and 15 cases of SLE. Five different types of response were observed: Type I through type V. 1. FAST was available to evaluate fetal well-being from 27 weeks of gestational age, although a nonstress test (NST) has been used after 31 weeks of gestational age. 2. Type IV was observed frequently in the case of coiling of the umbilical cord. 3. In acute fetal distress abnormality was detected by NST prior to FAST, but in latent fetal distress abnormality was detected by FAST prior to NST. 4. Cases classified as FAST types III and IV, which remained unchanged or deteriorated to III, IV or V were almost all characterized by poor fetal outcome. PMID- 1940555 TI - [A new criterion for hCG administration in human IVF programs: importance of serum LH levels]. AB - A new, simple criterion for hCG administration to induce ovulation for IVF is described. Serum LH levels were measured daily, and hCG was administered, independent of follicle size or estradiol levels, the night of the day when the LH level first exceeded the J level, defined as the minimum value + (the day 3 value-the minimum value) x 1/3. Based on this hCG criterion, the total and ongoing pregnancy percentages per cycle were 35% and 27%, respectively. It appears that the pregnancy rate decreases when hCG is administered one day before or one day after the criterion is met. Pregnancies resulting from hCG administration based on the criterion had a wide range both of dominant follicle diameter (14-21 mm) and estradiol level (229-2,050 pg/ml). The serum LH level is recommended as a useful parameter in timing hCG administration for IVF. PMID- 1940557 TI - [Microdetermination of developmental changes in the uptake of glucose by preimplantation mouse embryo]. PMID- 1940556 TI - Biophysical profile and its relation to fetal blood gas level obtained by cordocentesis. AB - Biophysical profile (BPP) score was assessed immediately before fetal blood sampling by cordocentesis in 150 fetuses referred to our hospital, 95 after and 55 before 30 weeks of gestation. In 95 fetuses after 30 weeks of gestation, 39 fetuses were evaluated with BPP scores of 12, 35 were from 8 to 11 and 21 were less than 7. In 55 fetuses before 30 weeks of gestation, 8 fetuses were evaluated with BPP scores of 12, 27 were from 8 to 11 and 20 were less than 7. pO2, pH and pCO2 in fetuses with a score less than 7, either before or after 30 weeks of gestation, (with a score less than 7) did not significantly differ, in comparison to the other two groups. No variables in the biophysical profile precisely reflect fetal hypoxemia, acidemia or hypercarbia. Since even the fetus with a BPP score of greater than 8 may not always be assured of well-being and not all fetuses with a score of less than 7 are necessarily in a deteriorated condition, it is necessary to evaluate fetal condition on the basis of fetal blood gas data obtained by cordocentesis, especially when the fetus is additionally handicapped by prematurity or morbidities such as growth-retardation. PMID- 1940558 TI - Alternative treatment for unexplained recurrent spontaneous abortion. PMID- 1940559 TI - [A case report of pregnancy associated with Crohn's disease maintained on enteral hyperalimentation]. PMID- 1940561 TI - [A study of the magnetic resonance image]. AB - MR imaging offers the superior evaluation of soft tissue structures without the use of ionizing radiation or intracapsular injection. In addition, the influence of MR imaging on the field of T.M.J. may be quite substantial. The purpose of this study is to demonstrate the principles of MR imaging, to determine the normal and abnormal T.M.J. imaging, and to compare MR imaging with transcranial, arthrography, tomography, and computed tomography. PMID- 1940560 TI - [Clinical study on treatment of internal derangement of the T.M. joint]. AB - The author has studied on treatment of internal derangement of the temporomandibular joint induced by incision of the retrodiscal ligament, and on an extracapsular surgical treatment method composed of lower repositioning of the mandibular condyle with oblique osteotomy of the ramus on the animals and 5 patients with internal derangement of the T.M. joint. To induce internal derangement on experimental animals, 5 Malaysian monkeys aging around 2 years and weighing about 3kg. were used, the retrodiscal ligament of the left temporomandibular joint was incised, and 1mm lower repositioning surgery of the condyle was performed 3 weeks after. The animals were observed and sacrificed on the 1st, 2nd, 3rd, 4th and 5th weeks thereafter, and the temporomandibular joints and their surrounding tissues were obtained to make microscopic specimens stained with Hematoxylin-Eosin and with Van Gieson method and patient treated by means of lower reposition surgery and 5 patients treated have been observed clinically. And 5 patients treated have been observed clinically. The results obtained were as follows: 1. Internal derangement of the T.M. joint occurred in by resecting retrodiscal ligament. 2. A lots of bone resorption on articular eminence was shown, 1-2 weeks after lower repositioning surgery. 3. Bone healing on articular eminence was shown, 3-5 weeks after lower repositioning surgery. 4. Displased articular disks came back to normal positions by lower repositioning surgery. 5. 5 patients with internal derangement completely treated by application of lower repositioning surgery. PMID- 1940562 TI - [Cytotoxicity evaluation of root canal sealers by fibroblast culture]. AB - This study was undertaken to evaluate the cytotoxic effects of 8 root canal sealers. Fibroblasts of human gingiva were employed to determine the comparative cytotoxicity of the 8 experimental materials. The results of this experiment were analyzed by counting the cells on the 2nd, 4th and 7th day. The results were as follows: 1. All experimental groups exhibited significant decrease of cell numbers in compared with control. All experimental groups showed cytotoxicity at 2, 4, 7 days (P less than 0.05). 2. All experimental groups except AH26 exhibited the decrease of mean of cell numbers with increasing time. 3. On the 7th day, AH26' Tubli-Seal and NOgenol showed lower cytotoxic effect than Apatite root sealer (Type I, II, III), N2 universal and Sealapex. 4. There was no statistical significance of cytotoxicity among the experimental groups (Type I, II, III) of Apatite root sealer (P greater than 0.05). PMID- 1940563 TI - [A case report of premolar autotransplantation]. AB - The patient was a 12-year-old female with Angle's Class II malocclusion accompanying congenital missing of upper premolar. The results were as follows: 1. After autotransplantation, orthodontic treatment time was 26 months. 2. In panoramic and periapical radiographs demonstrated closed root apex of transplanted tooth. 3. Autotransplanted tooth responses about vitality test. 4. Periodontal probing was within normal limits in the transplanted area. PMID- 1940564 TI - Oculomotor nerve palsy from posterior communicating artery aneurysm. AB - The mortality rate for posterior communicating artery (PCA) aneurysm with oculomotor nerve palsy is 33 per 100. The incidence of oculomotor palsy with PCA aneurysm varies from 34% to 56%. The classic presentation of a PCA aneurysm involving the oculomotor nerve is sudden onset of severe unilateral frontal headache, ptosis, a dilated and fixed pupil, and limitations of adduction, depression, and elevation of the eye. Carotid arteriography is diagnostic. This case is presented because of the high probability of being seen first by a primary care physician. Delay in clinical recognition and treatment can have dire consequences for the patient. PMID- 1940565 TI - Incidental ileal carcinoid associated with multiple urologic malignancies. AB - Although associated primary neoplasms frequently occur with carcinoid tumors, associated nonendocrine urologic malignancies are uncommonly encountered. We report the first case of an incidental ileal carcinoid associated with bilateral renal cell carcinoma and prostatic adenocarcinoma. PMID- 1940566 TI - ECG of the month. Cold turkey. Cardiac pacemaker. PMID- 1940567 TI - The Medicare peer review organization program: what every physician should known about PRO activities and how to handle notices. A report from the LSMS Physician/Patient Advocacy Committee. PMID- 1940569 TI - Traumatic perforation of the tympanic membrane. AB - Traumatic perforations of the tympanic membrane are not uncommon injuries. The various etiologies of this injury along with the appropriate evaluation will be discussed. The goal of this review is to enhance the nonotolaryngologist's knowledge of this condition and its treatment. PMID- 1940568 TI - Indigenous amebiasis. AB - A case of amebic anemia in a 53-year-old Louisianian prompted us to report it, in order to create awareness of such cases occurring in the absence of foreign travel. If one is cognizant of amebiasis it will be included in the differential diagnosis when it is proper to do so. PMID- 1940570 TI - Assessment of zinc nutriture. PMID- 1940571 TI - Biologic significance of the erythrocyte complement receptor: a primate perquisite. PMID- 1940572 TI - Ecto 5' nucleotidase (5'NT) as a sensitive indicator of human zinc deficiency. AB - Ecto 5' nucleotidase (5'NT) is an integral plasma membrane enzyme located on most mammalian cells, and it is zinc dependent. We assayed 5'NT activity in the lymphocytes of two groups of subjects. The first group of six subjects had a mild state of zinc deficiency, as measured on the basis of zinc levels in lymphocytes, granulocytes, and platelets, but were otherwise healthy. They received 50 mg zinc as acetate orally for 12 weeks. The second six subjects were normal human volunteers in whom a mild state of zinc deficiency was induced experimentally by dietary techniques (4.2 to 5.6 mg daily zinc intake). For the assay of 5'NT, intact lymphocytes were incubated with 8-14C-labeled inosine monophosphate as substrate. Product and substrate were separated by thin-layer chromatography. Zinc level in cells was measured by flameless atomic absorption technique. In the first group of subjects with zinc deficiency, the decreased activity of 5'NT was corrected and the cellular zinc levels were normalized by oral zinc supplementation (p less than 0.01). In the second group of subjects, the baseline data were compared with those in early zinc depletion (4 to 8 weeks) and late depletion periods (greater than 20 weeks). A decrease in the activity of 5'NT was observed during the early zinc depletion phase. Zinc levels in lymphocytes, granulocytes, and platelets decreased significantly only during the late zinc depletion phase (p less than 0.01). Plasma zinc level did not change even during the late zinc depletion phase. Our studies show that 5'NT activity may be a sensitive and useful indicator of mild deficiency of zinc in human subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940573 TI - Activated factor IX-antithrombin III complexes in human blood: quantification by an enzyme-linked differential antibody immunoassay and determination of the in vivo half-life. AB - An enzyme-linked immunoassay has been developed to quantitate the activated human factor IX-antithrombin III complex (IXa-AT III). Test plasma was absorbed onto barium citrate and eluted to remove free antithrombin III (AT III). The IXa-AT III complex in the eluate was then measured by using polystyrene balls coated with immobilized rabbit anti-AT III antibody-binding fragments and anti-factor IX (anti-FIX) antibody-binding fragments labeled with beta-D-galactosidase. The assay was very sensitive, detecting a concentration as low as 0.15 fmol/assay/100 microliters plasma, which corresponds to as little as 0.002% of activated FIX in plasma. Experiments with purified FIX, IXa-alpha, AT III, IXa-AT III, normal plasma, AT III-depleted plasma, and FIX-deficient plasma demonstrated that the assay is specific. IXa-AT III generation could be detected in normal native whole blood within 2.0 minutes after venipuncture. The complex could not be detected in native whole blood from patients with severe hemophilia B even at 1 hour after venipuncture. The mean plasma level of IXa-AT III in healthy adults (n = 32, ages 23 to 54 years) was 9.67 +/- 2.86 pmol/L (mean +/- SD), whereas in eight patients with disseminated intravascular coagulation levels ranged from 11.7 to 35.0 pmol/L. The IXa-AT III titer was significantly reduced in three patients with severe factor VII deficiency (5.70 +/- 1.99 pmol/L) but was normal in three patients with severe factor XI deficiency (11.2 +/- 1.59 pmol/L). Purified IXa-AT III was cleared in vivo in rabbits with a half-life value of 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940574 TI - An inhibitor of tumor necrosis factor found in pleural effusions. AB - Tumor necrosis factor (TNF) has significant biologic effects. Inhibitors of TNF have been isolated from urine and blood. We studied pleural fluid from 22 patients with benign or malignant effusions. Pleural macrophages from these effusions were capable of releasing TNF, especially when stimulated with lipopolysaccharide. The cell-free supernatant from some of these pleural effusions contained an inhibitor of TNF. Fluid from 12 malignant effusions contained an inhibitor of 17% +/- 15.4% (mean +/- SD) of 500 U/ml of TNF activity, whereas the mean inhibition in 10 benign effusions was 2% +/- 5.6% (p less than 0.05). Only one of 10 benign effusions had more than 10% inhibitory activity. This inhibitor was found to be heat sensitive and unaffected by dialysis, and the molecular weight of at least one of the inhibitors was 60 to 80,000 daltons. Enzyme digestion studies were consistent with a protein portion being the major determinant of activity. We conclude that some malignant effusions contain an inhibitor of TNF activity. PMID- 1940575 TI - Influence of plasma and red cell factors on the rheologic properties of oxygenated sickle blood during clinical steady state. AB - Yield stress is a sensitive index of blood fluidity at low shear stress. Using a method that measured the stress required to cause motion of a thin sedimenting layer of red cells, we found significant elevations of yield stress in patients with homozygous sickle cell anemia during clinical steady state. Mixing studies of sickle cells in normal plasma and buffered saline and of normal red cells in sickle plasma showed (1) that the increased yield stress of sickle blood was not due to differences between sickle and normal plasma factors and (2) that yield stress of sickle cells was not increased in the absence of plasma proteins. Multivariate regression analysis was performed to determine the dependence of sickle blood yield stress on several red cell and plasma factors. The yield stress measurements were normalized for differences in plasma fibrinogen concentration. Other factors studied included cell density, fetal hemoglobin concentration, alpha globin genotype, cell deformability as measured by high shear viscosity, and fibronectin and von Willebrand factor concentrations. Cell density was the primary determinant of yield stress. Measurements of yield stress on density fractionated sickle cells confirmed that the increased yield stress of sickle blood was due to the dense sickle erythrocyte. We conclude that the increased yield stress of sickle blood during clinical steady state was due to an abnormal interaction between the dense sickle cell membrane and plasma protein(s). PMID- 1940576 TI - Unsaturated fatty acids and lipoxygenase products regulate phagocytic NADPH oxidase activity by a nondetergent mechanism. AB - Neutrophils produce reactive oxygen species (superoxide anion [O2-]) via activation of reduced nicotinamide dinucleotide phosphate oxidase. In the intact neutrophil, this enzyme can be activated by increases in cytosolic calcium, protein kinase C, and unsaturated fatty acids such as arachidonic acid, all of which are produced on stimulation by chemotactic peptides like N-formyl-methionyl leucyl-phenylalanine. Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) do not stimulate the respiratory burst but instead prime the cell for an enhanced response by an appropriate stimulus. We examined the role and potential mechanisms of free fatty acids in stimulating or priming neutrophil O2- production. Except for arachidonic acid, the ability of an unsaturated fatty acid to stimulate O2- production was not correlated with its critical micellar concentration, suggesting that detergent action was not the primary mechanism. Eicosatetraynoic acid, which blocks further arachidonate metabolism by the 5- and 15-lipoxygenases, inhibited O2- production by arachidonic acid. However, eicosatetraenoic acid did not inhibit other unsaturated fatty acid or phorbol ester-induced O2- production, suggesting that the effects of arachidonic acid were mediated at least in part by a metabolite. The same negatively charged, unsaturated fatty acids that directly stimulated O2- production when used in micromolar concentrations also primed neutrophils when added in nanomolar concentrations. The amount of a priming response was independent of chain length or number of double bonds. The magnitude of priming observed in GM-CSF-treated cells could be reconstituted with combinations of arachidonic acid and its lipoxygenase products.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940578 TI - Relative enrichment of hematopoietic progenitor cells: efficiency of a repeated density centrifugation. AB - Low-density cells were prepared from 11 bone marrow samples by centrifugation on Ficoll-sodium diatrizoate. Repeated density gradient centrifugation of the cells collected from the interface of the first gradient removed most nonnucleated erythroid cells. A mean of 47.9% (19.4% to 76.0%) of the mononuclear cells collected after the initial centrifugation were recovered from the interface of the second gradient, whereas 13.3% (3.7% to 34.9%) of the MNCs were counted in the high-density pellet and 38.9% (3.8% to 65.7%) of the MNCs were lost unspecifically. In contrast, a mean of 71.7% (43.0% to 91.3%) of the colony forming units were recovered from the interface after the second centrifugation (as determined by colony formation assays), whereas only 3.2% (0.5% to 7.0%) were found in the high-density pellet. The unspecific loss of colony-forming units was 25.1% (1.7% to 51.4%). The results demonstrate a relative enrichment of colony forming units in the culture assay by 1.7 times (average). The method is recommended as an additional preparative step before fluorescence-activated sorting of viable cells, because removal of most erythrocytes and late normoblasts strongly reduces the time required for sorting. PMID- 1940577 TI - Reperfusion of ischemic skeletal muscle causes erythrocyte hemolysis and decreases subsequent oxidant-mediated lung injury. AB - A prior transient hindlimb ischemia/reperfusion (I/R) insult decreased acute lung injury in rats subsequently treated with cobra venom factor. I/R-mediated protection was associated with erythrocyte hemolysis, increased plasma catalase activity, and increased plasma hydrogen peroxide scavenging activity. In contrast, hindlimb I/R did not increase lung catalase activity, and large amounts of injected catalase were required to increase lung catalase activity. The results suggest that limited I/R in one organ can induce systemic processes that may decrease a subsequent O2 metabolite-mediated injury in another distant organ. The mechanism may involve release of catalase from hemolyzed erythrocytes at levels that are not sufficient to measurably increase total lung catalase activity. PMID- 1940579 TI - The irradiation-associated decline in the in vivo uptake of glucose observed in rats fed fish oil is prevented by feeding a diet enriched in saturated fatty acids. AB - Previous in vitro studies have shown that abdominal irradiation diminishes the uptake of many nutrients and that the extent of this effect can be modified by varying the type of dietary fatty acid. This study was undertaken to determine (1) the effect of dietary fish oil fatty acids (FO) on the in vivo absorption of D-glucose and (2) the effect of feeding isocaloric diets containing FO or beef tallow (BT) on the in vivo uptake of glucose 2 weeks after a single 600 cGy exposure to abdominal irradiation from a 137Cs source. Feeding FO reduced the jejunal and ileal maximal transport rate (Vmax) and Michaelis constant (Km) for glucose uptake in nonirradiated control animals. In irradiated rats the Vmax was higher and the Km was lower in animals fed BT than in those fed FO. The passive component of glucose uptake was higher in control rats fed FO than in those fed BT yet was lower in irradiated animals fed FO compared with those fed BT. Although the value of the Km fell with FO, the effective resistance of the intestinal unstirred water layer rose so that the uptake of lower concentrations of glucose was undisturbed. However, FO reduces the uptake of higher concentrations of glucose as a result of a decline in the value of the Vmax that is sufficiently large to override the enhanced passive permeability of the intestine to glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940580 TI - Differences in thromboxane A2 synthesis by megakaryocytes and platelets. AB - The capacity for thromboxane A2 synthesis in response to exogenous arachidonic acid, calcium ionophore A23187, thrombin, and collagen was studied during megakaryocyte maturation. Studies were performed in (1) isolated megakaryocytes not separated, (2) isolated megakaryocytes separated into subgroups at different stages of maturation, and (3) washed platelets. When comparisons were based on equal amounts of cell protein (10(5) megakaryocytes vs 10(8) platelets), isolated megakaryocytes, not separated into subgroups, responded to exogenous arachidonic acid with synthesis of thromboxane A2 equal to that of platelets from the same animals at their respective times of maximum synthesis (30 minutes vs 10 minutes). In similar fashion, megakaryocytes and platelets synthesized thromboxane A2 from endogenous arachidonic acid at the same minimum concentration of A23187, 0.1 mumol/L, and showed equal maximum synthesis at 1 mumol/L (167 +/- 9 pmol and 150 +/- 18 pmol, respectively). In contrast, maximum thromboxane A2 synthesis in response to thrombin (10 U/ml) was three times higher in platelets than in megakaryocytes (230 +/- 15 pmol and 74 +/- 5 pmol, respectively), and synthesis in response to collagen (20 micrograms/ml) was 20 times higher in platelets (130 +/- 20 pmol vs 7 +/- 1.2 pmol). When synthesis was studied in isolated megakaryocytes at different stages of maturation, the capacity for thromboxane A2 synthesis was established in immature megakaryocytes but was not fully developed in the most immature megakaryocytes. Synthesis in response to thrombin was not significantly enhanced by megakaryocyte maturation. Thus the ability to metabolize arachidonic acid occurs early during megakaryocyte maturation, but the ability to respond to thrombin and collagen is only fully established in platelets. PMID- 1940581 TI - High hemoglobin A2 beta-thalassemia. PMID- 1940582 TI - Christian Doppler (1803-1853): an ingenious theory, an important effect. PMID- 1940583 TI - Radical thoughts about kidneys. PMID- 1940584 TI - Evaluation of the role of reactive oxygen species in doxorubicin hydrochloride nephrosis. AB - In subcellular systems, doxorubicin hydrochloride (ADR) leads to the generation of reactive oxygen species such as superoxide anion. Because reactive oxygen species have been shown to be important mediators of glomerular injury in several animal models, we sought to determine whether reactive oxygen species play a significant role in the pathogenesis of ADR-induced nephrotic syndrome in the rat. Rats pretreated with a variety of free radical scavengers (superoxide dismutase conjugated to polyethylene glycol [PEGSOD], catalase, catalase plus PEGSOD, dimethylsulfoxide, desferoxamine, or n-acetyl cysteine) had no significant reduction in proteinuria at 3 weeks after ADR administration when compared with rats receiving ADR in the absence of scavengers. No evidence was seen of increased lipid peroxidation or depletion of reduced glutathione in renal cortex tissue obtained up to 24 hours after administration of ADR. No changes were seen in the renal cortical levels of either enzyme activity or immunoreactive protein for the endogenous antioxidant enzymes superoxide dismutase (either the Mn or CuZn forms) or catalase after ADR. Total and MnSOD activities in glomeruli isolated from rats after ADR administration fell significantly, though CuZnSOD activity was increased. The effect of ADR on cultured rat mesangial or epithelial cells was also evaluated. ADR inhibited growth of both cell types at concentrations of approximately 5 to 10 mumol/L, an order of magnitude below the reported Michaelis-Menten constant for ADR-induced superoxide production. The growth inhibitory effect could not be prevented in either cell type by treatment with PEGSOD, catalase, or PEGSOD plus catalase. This combination of results from in vivo and in vitro studies provides no evidence for an important role of reactive oxygen species in ADR nephrosis and suggests that other known mechanisms of ADR cytotoxicity, such as interference with DNA metabolism, mediate the glomerular injury. PMID- 1940585 TI - Characterization of the binding of thrombospondin to human platelets and its association with the platelet cytoskeleton. AB - To characterize the interaction between thrombospondin and human platelets, thrombospondin was purified from the supernatant of thrombin-activated human platelets, labeled with iodine 125, and allowed to interact with the washed platelets. With concentrations of 10 to 50 micrograms/ml, only minute amounts of 125I-labeled thrombospondin bound to resting platelets or to platelets activated by adenosine diphosphate. In contrast, when platelets were stimulated with thrombin, binding increased fivefold to sixfold in a time-dependent and 125I labeled thrombospondin concentration-dependent manner. Binding of 125I-labeled thrombospondin to thrombin-activated platelets required the presence of divalent cations, proceeded concomitantly with platelet release, and at a concentration of 1 nmol/L thrombin, reached a maximum of 2200 +/- 260 molecules of 125I-labeled thrombospondin bound per platelet. After its binding to platelets, 125I-labeled thrombospondin was not internalized, because up to 85% of the 125I-labeled thrombospondin was dissociated from the cell surface by adding ethylenediaminetetraacetic acid. Using various experimental approaches, including studies with severe type I thrombasthenic platelets, we further demonstrated that the interaction of 125I-labeled thrombospondin with thrombin-stimulated platelets occurred as a fibrinogen- and fibrin-independent process, and that the glycoprotein IIb-IIIa complex did not function as a physiologic plasma membrane receptor for 125I-labeled thrombospondin. Last, about 60% of the 125I-labeled thrombospondin molecules bound to the platelet surface were found to be associated with the platelet cytoskeleton recovered from platelets solubilized with Triton X-100. On Western blot analysis, this cytoskeletal fraction lacked detectable glycoprotein IV, the putative platelet receptor for thrombospondin. These results suggest that on the surface of thrombin-activated platelets, a fraction of 125I-labeled thrombospondin does not associate with glycoprotein IV but instead with other plasma membrane components that have yet to be identified. PMID- 1940586 TI - Diagnosis and characterization of presymptomatic patients with Wilson's disease and the use of molecular genetics to aid in the diagnosis. AB - Wilson's disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. Although fatal if untreated, the condition can be treated effectively. Autosomal recessive inheritance indicates that siblings of affected patients are at 25% risk of having the disease. If they are diagnosed prior to becoming symptomatic, affected siblings can be kept free of symptoms by prophylactic therapy. In this paper we have examined the utility of copper-related variables, along with other clinical and molecular findings, in identifying those siblings of affected patients who should be further evaluated with a liver biopsy. Data are presented on a series of 13 presymptomatic patients in whom we have made the diagnosis of WD based on liver biopsy findings. Signs of liver disease were present in 12 out of 13 cases. The classic, noninvasive, screening approaches that we evaluated were not adequate to identify all cases of WD in this group of patients. These included positive Kayser-Fleischer (KF) rings, elevated liver serum alanine transferase, elevated urine copper, or elevated plasma nonceruloplasmin copper. We have introduced the use of molecular genetics for screening siblings of affected patients for WD. We show that a probe from the linked retinoblastoma (RB) gene can be very helpful in problem cases. However, at this time, the quantitative determination of liver copper concentration remains as the definitive diagnostic criterion. PMID- 1940587 TI - Treatment of Wilson's disease with zinc. IX: Response of serum lipids. AB - Zinc therapy in Wilson's disease is a lifelong treatment to prevent reaccumulation of copper. Previous reports have shown that in normal male subjects, zinc ingestion has reduced high-density lipoprotein cholesterol level. This finding raises the possibility that lifelong zinc therapy could be atherogenic. In the present work, the effects of zinc therapy on serum lipids over a period of years is evaluated in patients with Wilson's disease. Zinc therapy reduces total cholesterol level by about 10% in both sexes and reduces high-density lipoprotein cholesterol level by about 20% in male patients. The mechanisms of these interesting effects of zinc on cholesterol metabolism are unknown. The coronary heart disease risk factor is not changed significantly by zinc therapy in either sex, and further, it remains below average in these patients after zinc therapy. We conclude that zinc therapy in Wilson's disease is not atherogenic. PMID- 1940588 TI - A predictive model for the clearance of soluble phospholipase A2 during septic shock. AB - Circulating phospholipase A2 (PLA2) has been recognized as a mediator of cardiovascular collapse in septic shock. Proximal mediators of endotoxemia, including tumor necrosis factor and interleukin 1, induce PLA2 synthesis and release, but the factors regulating PLA2 elimination are unknown. Similarly, the kinetics of PLA2 clearance during recovery from septic shock have not been examined. An autoregressive mathematical model was developed to describe the rate of PLA2 clearance during the recovery phase of septic shock. This model (which estimates that the current day's PLA2 level is 77% of the previous day's level), accounted for 89% of the variability seen in the data. The estimated circulating half-life of soluble PLA2 in septic shock in man was 32 hours. Since elevation in serum PLA2 activity is closely associated with bacteremia or endotoxemia, a significant deviation from predicted PLA2 values may denote impending relapse. PMID- 1940590 TI - Localization of human blood phenol sulfotransferase activities: novel detection of the thermostable enzyme in granulocytes. AB - Phenol sulfotransferases (PSTs) catalyze the sulfate conjugation of catecholamines and a variety of phenolic compounds. Thermolabile and thermostable forms of PST exist in human tissue. Blood component thermostable PST activities have proved useful as measures of the enzyme activities in other tissues such as the liver. The most thoroughly studied blood component is the human platelet, which contains both thermolabile and thermostable PST activities. Partial localization of PST activity in blood has been characterized only for thermolabile PST. We performed the studies reported here to define the cellular and subcellular localization of both thermolabile and thermostable PST activities in blood elements. Blood samples from four adults were pooled and aliquots for platelet studies were anticoagulated with ethylenediaminetetraacetic acid. Aliquots for studies of granulocytes, mononuclear cells, and erythrocytes were defibrinated to avoid platelet contamination and were separated through Ficoll Hypaque gradients. Cytosol thermolabile PST activities assayed with dopamine as the substrate and expressed as a percent of the total thermolabile PST activity per milliliter of whole blood were as follows: platelets, 97%; granulocytes, 0.6%; mononuclear cells, 0.7%; and erythrocytes, 0.4%. Cytosol thermostable PST activities measured with p-nitrophenol were as follows: platelets, 77% of the total activity; granulocytes, 19%; mononuclear cells, 1.2%; and erythrocytes, 0.5%. Plasma and membrane-bound activities were less than 2.3% of total activities for each form. Because granulocyte thermostable PST was present in an amount greater than expected, it was further characterized. The Michaelis-Menten constant values for p-nitrophenol and 3'-phosphoadenosine-5'-phosphosulfate were 1.13 mumol/L and 0.6 mumol/L, respectively. The pH optimum of 6.6, a 50% inhibitory concentration for 2,6-dichloro-4-nitrophenol of 1.0 mumol/L, and retention of 56% of activity after preincubation at 45 degrees C for 15 minutes were the same for the granulocytes as for platelet thermostable PST. In summary, our study confirms and extends our knowledge of localization of blood thermolabile PST. Our data define for the first time the localization of blood thermostable PST and highlight the substantial contribution of granulocyte thermostable PST activity. Granulocytes represent an easily obtained nucleated cell for the study of human thermostable PST. PMID- 1940589 TI - Naloxone increases water and electrolyte excretion after water loading in patients with cirrhosis and ascites. AB - Endogenous opioids may be involved in the pathogenesis of ascites and edema in patients with liver cirrhosis. We administered the opioid antagonist naloxone (5 mg bolus followed by a 0.06 mg/min infusion) to eight male patients with alcoholic cirrhosis and ascites and to five healthy age- and sex-matched control subjects and determined the effects of naloxone on water and electrolyte excretion after a nonsustained water load (20 ml/kg). In comparison with saline vehicle infusion carried out in the same subjects, naloxone administration resulted in a 50% increase in urine output and creatinine clearance and twofold increases in sodium and potassium excretion in patients with cirrhosis. Fractional sodium and potassium excretion, minimal urinary osmolality, plasma vasopressin and aldosterone levels, arterial blood pressure, and heart rate were not affected by naloxone treatment. The diuretic effect of naloxone was not observed in control subjects. Plasma naloxone levels were about six times higher in patients with cirrhosis than in control subjects (probably because of impaired metabolism of the drug) but only a weak correlation was found between drug levels and the degree of diuresis observed. The diuretic effect of naloxone may be related to an increase in glomerular filtration rate, possibly in conjunction with altered tubular reabsorption. PMID- 1940591 TI - Problem solving and transfer. AB - Problem solving is an important yet elusive educational goal. This article briefly reviews the research on the components of problem solving and two mechanisms for fostering the transfer of problem-solving strategies--low-road transfer and high-road transfer. The interactions between these two mechanisms and two types of content (domain-specific knowledge and higher order thinking) are then discussed. Exploratory research on one of the interactions (low-road transfer of higher-order thinking) is summarized, with a particular focus on the performance of students with disabilities. Finally, some implications for curriculum and instruction are outlined. PMID- 1940592 TI - Shared understandings: structuring the writing experience through dialogue. AB - When teachers view writing as a social process in which authors write for real audiences and authentic purposes, they change their instruction accordingly to meet the needs of writers with learning disabilities. As more experienced members of a larger community of writers, teachers play a primary role in apprenticing students into the inherently social functions of writing. Through teacher-student dialogues about the complexities of the writing process, students gradually develop and control their own writing "voice" as they use and transform the shared understandings of the group process. Text structure, writing strategies, and metacognitive knowledge of the writing process provide opportunities for teachers and students with learning disabilities to interact and create shared understandings about the composition process. This article reviews some recent attempts to use text structures and the writing process as frameworks to guide the composition dialogue. PMID- 1940593 TI - The fundamental skills of higher order thinking. AB - It may be possible to teach reasoning strategies to subjects with poor reasoning, including many subjects with learning disabilities (LD), using curriculum designed around a sameness analysis. The higher order thinking skills of analogical and logical reasoning are defined using the sameness analysis methodology. The sameness in the strategy for forming a generalization from experience is called "reasoning by analogy," while the sameness in the strategy for applying generalizations is described by the syllogism (logical reasoning). The research base for effective instruction in analogical and logical reasoning, particularly with subjects with LD, is summarized. The wide applicability of reasoning by analogy and by syllogism as complementary strategies is illustrated through their use in a critical review of the editorial page of a daily newspaper, and in linking content material in several domains. PMID- 1940594 TI - Instructional and curricular requisites of mainstreamed students with learning disabilities. AB - The successful integration of students with learning disabilities into mainstream reading classes may require teachers to adapt instruction and curricula in major ways. In this article, we discuss the relation between the instruction prescribed by standardized commercial curricula and the reading achievement of mainstreamed students with learning disabilities and other low-performing nonhandicapped students. An instructional template designed to complement commercially published reading lessons is described and its effects on the reading achievement of mainstreamed students with learning disabilities examined. Next, the limitations of generic instructional procedures to rectify the deficiencies of mainstream curricular programs for students with greater-than-average instructional needs are reviewed. We conclude with a discussion of the complexity of educating instructively needy learners in mainstream settings and the significance of well designed instruction. PMID- 1940595 TI - Implications of the sameness analysis for curriculum developers and curriculum users. PMID- 1940596 TI - Toward a scientific pedagogy of learning disabilities: a sameness in the message. AB - The development of a scientific pedagogy of learning disabilities as called for by Kirk and Bateman (1962) requires the rendering of a science of learning disabilities and a pedagogy derived from that science. But such a pedagogy is necessarily incomplete if it fails to recognize that the structure of the curriculum significantly shapes the act of teaching students identified as learning disabled. The current thinking about curricula is that the universe of information that a curriculum program comprises need only be organized around subject area topics (e.g., mathematics, reading, language arts, science, social studies) and hierarchically arranged in a scope and sequence that has as its main characteristic the general ordering of skills from simple to complex. For all practical purposes, information is viewed as raw material (Kaufman et al., 1990) that can be nominally organized and readily packaged. The information is then consumed as curriculum that requires little or no transformation of its form or structure. The articles in this series of the Journal of Learning Disabilities provide examples of how transforming information by identifying and developing curricula around structural samenesses can lead to a pedagogy that is efficient and effective. The development of a scientific pedagogy of learning disabilities requires that the field acknowledge the importance of curriculum structure and the complexity of information. The field must also examine the intricacies of designing curricula with the same kind of commitment and passion it has demonstrated in the last 30 years in investigating the etiology and organic basis of learning disabilities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940597 TI - Neverstreaming: prevention and early intervention as an alternative to special education. PMID- 1940599 TI - Word and letter reversals in persons with dyslexia. PMID- 1940598 TI - Vocabulary training for children with dyslexia. AB - A vocabulary training program, using the parents as sole instructors, led to significant and lasting improvements in word knowledge and lexical access speed for 13 adolescents with dyslexia. Furthermore, when the trained words matched the current vocabulary age of the child, the improvement generalized to untrained words. PMID- 1940600 TI - A review of social interventions for students with learning disabilities. AB - Twenty-two studies are reviewed that report the effects of social skills training and intervention with 572 children identified as learning disabled between 5 and 19 years of age. These studies are reviewed to examine characteristics and components of intervention effectiveness. Age and sex of subjects, grade grouping, group size, intervention duration, intervention procedures, subject selection, and type of interventional model are examined to find patterns that reflect intervention success. Several intervention characteristics and components are associated with social intervention effectiveness: selecting subjects who had social skills difficulties or low peer acceptance, using cognitive-behavioral intervention procedures, providing individual or small group instruction, and applying long-term intervention and training. Discussion focuses on difficulties in comparing studies to determine intervention effectiveness through the examination of outcome measures, a call for revisions in future reporting of social interventions in the literature, and those intervention factors that relate to increases in peer acceptance. PMID- 1940601 TI - A change in legal status: an overlooked dimension in the transition to higher education. AB - The transition from high school to college entails a change in legal status for individuals with learning disabilities. As students leave high school and the dominion of P.L. 94-142, they enter a setting structured by Section 504 of the Rehabilitation Act of 1973. How does this change in legal status affect student rights and responsibilities? Do students with learning disabilities need specific skills to facilitate their legal transition into higher education? Is current transition programming addressing To investigate these questions, basic provisions of P.L. 94-142 and Section 504 were reviewed. Implications of the change in legal status were discussed, and existing transition programs were examined. Guidelines are proposed for incorporating legal transition skills in future transition programming. PMID- 1940602 TI - The form and substance of secondary resource models: content area versus skill instruction. AB - The provision of core content coursework instruction by secondary learning disability (LD) teachers has increased dramatically in recent years. This article describes the results of a study that compared the perceptions of 48 LD content teachers and 45 basic skills teachers concerning (a) their relationship with the mainstream, (b) curricular structure, (c) instructional methodology, and (d) the behavioral characteristics of their students. Differences in the teachers' judgements were evaluated by t tests. Results indicated that, despite pronounced differences in caseloads and class sizes, the two groups are very similar in how they evaluate their instructional emphases. The data also indicate that the groups differ not so much in how they teach as in how they perceive their interactions and their students' with the mainstream. PMID- 1940603 TI - A comparison of three methods of reading-while-listening. AB - This study tries to distinguish between the effects of spoken text in reading while-listening (RwL) and those of text repetition by determining whether repeated RwL of the same text leads to better results than RwL of different texts. Moreover, it is investigated whether the results of RwL can be improved by asking the reader to detect mismatches between written and spoken texts. Subjects were 36 young backward readers (25 boys, 11 girls) from the Netherlands. Mean age was 111 months. With all three methods a practice effect was found for texts as well as for single words. Reading the same text, however, did not lead to better results than reading different texts. Nor were the effects of RwL of different texts improved by mismatch detection. Only the reading speed for the training texts increased following text repetition and mismatch detection. PMID- 1940604 TI - Psychopharmacological intervention. II: Teacher perceptions of psychotropic medication for students with learning disabilities. AB - The perceptions, knowledge, and opinions of 104 teachers of students with learning disabilities regarding medication used with their students were investigated. The students' doctors were perceived as the professionals primarily responsible for making the decision to have the student either placed on or taken off medication. The teachers indicated that global impressions and direct behavioral observations were used to assess the effects of medication but that they would prefer to use behavioral observations and rating scales. Hyperactivity and delusions/hallucinations were perceived as the problems most likely to lead to medication. Less than 15% of the teachers indicated that their professional preservice training had provided them with sufficient information on the use of medication for children with behavior problems, and less than 20% had a similar opinion regarding their inservice training on the same topic. PMID- 1940605 TI - Prevalence of adoptees among special education populations. AB - A statewide survey of public and private schools was conducted to determine the prevalence of adoptees among children classified for educational purposes as neurologically impaired (NI), perceptually impaired (PI), or emotionally disturbed (ED). Results indicated that adopted children were overrepresented in these special education populations, accounting for 6.7% of NI students, 5.4% of PI students, and 7.2% of ED students. Implications of the findings for educational and clinical intervention are discussed. PMID- 1940606 TI - Positive mood and math performance. AB - Two studies are reported that assessed the impact of positive moods on students' feelings of self-efficacy and math performance. In the first study, 32 black and Hispanic girls and boys in the third to fifth grades, who had been identified by teachers as at risk for school failure, and a control sample of normally achieving classmates served as subjects. In the second study, 15 males and 3 females in junior high and high school attending a private school for students with learning disabilities served as subjects. In both studies, students were randomly assigned to a positive-mood induction condition or a no-treatment control condition. Following this, they completed a measure of self-efficacy for math and were then given 5 minutes to do 50 math problems. In both studies, analyses of covariance using standardized math scores as the adjustor variable found that children in the positive-mood condition completed significantly more problems accurately than children in the no-treatment control condition. In addition, in the junior high and high school sample, students in the positive mood induction condition expressed greater self-efficacy for math than students in the control condition. The results of these two studies raise many questions about the role of affect, positive and negative, in the learning and performance of students with learning disabilities that researchers and teachers might explore. PMID- 1940607 TI - A review of states' criteria and procedures for identifying children with learning disabilities. AB - The purpose of this study was to investigate whether (a) states have altered their definitions and/or eligibility criteria for learning disabilities (LD) since the last review; (b) states have specified-IQ cutoffs below which a child would not be eligible for LD services; (c) the types of methods states use to quantify an ability/achievement discrepancy vary; and (d) an increase in the number of children identified as LD is related to the method or criterion used to quantify an ability/achievement discrepancy. States' guidelines and/or information obtained from state directors of special education were analyzed for all states and the District of Columbia. Results of the review revealed that 40% of states had revised their guidelines between 1988 and 1990; 76% of the states specified a method for determining an ability/achievement discrepancy and the method recommended most frequently was the standard score comparison method. No significant differences were obtained between type of discrepancy method employed by a state and its yearly increase in LD. However, a significant relationship existed between magnitude of a state's ability/achievement criterion and its yearly increase in LD from 1987-88 to 1988-89. The review also revealed an increase in the number of states that specified an IQ cutoff below which a student would not qualify for LD services. PMID- 1940608 TI - Identifying students with learning disabilities: the effect of implementing statewide guidelines. AB - Methods for identifying students with learning disabilities continue to be an area of controversy. The present investigation examined the impact of implementing statewide guidelines for the identification of these students. Data were collected from multidisciplinary team reports on 718 students with learning disabilities who were referred and labeled during the 1983-84 school year (before implementation of statewide learning disability guidelines) and 790 students who were identified during 1987-88 (after implementation of the guidelines). The results of the study revealed that the statewide guidelines significantly changed the characteristics of students who were identified. After the implementation of the guidelines, students with much more severe academic problems were identified. These students were much more likely to have a severe discrepancy and be chronically failing in the regular classroom. However, even with explicit, widely accepted guidelines, approximately one third of all students identified in 1987 88 failed to meet the stated criteria for identification. The implications of these findings for professional practice and future research are discussed. PMID- 1940609 TI - Preschool literacy experience and later reading achievement. AB - During their children's preschool years, parents were asked about the frequencies of adult reading, parent-child reading, and children's solitary book activities in the home. Parental responses were compared for three groups of children defined according to the parents' reading skills and the children's reading achievement in Grade 2. The results indicated that the 22 preschoolers who became poorer readers had less frequent early literacy-related experiences than the 34 children who became better readers. PMID- 1940610 TI - Production of granulocyte-macrophage colony-stimulating factor or GM-CSF-like growth factor by rat thymic epithelial cell line. AB - An epithelial cell line, IT-45R1, has been established from a thymus of normal Wistar rat and was found to produce growth factor which stimulated the proliferation of bone marrow cells. This growth factor induced the formation of colonies composed of macrophages, granulocytes, or both, in semi-solid medium and stimulated the proliferation of an interleukin 3 (IL3)/granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent clone. Neither IL3-dependent clone nor IL6-dependent clone responded to IT-45R1 factor. Additionally, IT-45R1 factor acted on both rat and mouse bone marrow cells but not on human bone marrow cells. Molecular weight of IT-45R1 factor was 30 kD and its isoelectric point was 4.5. To determine whether IT-45R1 factor is GM-CSF or not, Northern blot analysis and neutralization with anti-mouse GM-CSF antibody were carried out. IT-45R1 expressed GM-CSF mRNA, but neither M-CSF nor IL6 transcripts. However, antiserum specific for mouse GM-CSF did not neutralize IT-45R1 factor. Taken together, a rat thymic epithelial cell line, IT-45R1, constitutively produces GM-CSF or GM CSF-like growth factor. PMID- 1940611 TI - Effect of interleukin-1, GM-CSF, erythropoietin, and lithium on the toxicity associated with 3'-azido-3'-deoxythymidine (AZT) in vitro on hematopoietic progenitors (CFU-GM, CFU-MEG, and BFU-E) using murine retrovirus-infected hematopoietic cells. AB - The drug 3'-azido-3'-deoxythymidine (AZT), a synthetic thymidine analogue, has been used clinically in the management of acquired immune deficiency syndrome (AIDS). The drug is an effective antiviral agent due to its ability to block reverse transcriptase activity. This action of AZT was demonstrated in the Rauscher leukemia virus (RLV)-induced murine erythroleukemia model system. Unfortunately, associated with AZT has been the development of hematopoietic toxicity manifested by anemia, neutropenia, and overall bone marrow suppression. Hematopoietic growth factors (GM-CSF, erythropoietin), cytokines (interleukin-1), and agents known to potentiate hematopoiesis (lithium) have been demonstrated to modulate drug and/or radiation-induced hematopoietic toxicity. We report the results of further studies designed to investigate the ability of GM-CSF, erythropoietin, interleukin-1, and lithium to modulate AZT toxicity on murine hematopoietic granulocyte-macrophage (CFU-GM), megakaryocytic (CFU-Meg), and erythroid (BFU-E) progenitors cultured from bone marrow and spleen cells from mice infected with RLV. Hematopoietic progenitors from either normal or RLV infected animals when exposed to AZT demonstrated concentration-dependent toxicity and differed for each progenitor with BFU-E being the most sensitive (ID50 concentration, 5 x 10(-9) M) and CFU-GM the least sensitive (ID50 concentration, 5 x 10(-5) M). As has been previously demonstrated using normal murine hematopoietic progenitors, when cultured with RLV-infected marrow or spleen cells, addition of GM-CSF, Meg-CSF or erythropoietin failed to inhibit AZT toxicity in vitro on CFU-GM, CFU-Meg, and BFU-E, respectively. However, in the presence of interleukin-1 (recombinant human IL-1 alpha, 30 ngm) or lithium chloride (ultra-pure, 1.0 mM), AZT toxicity CFU-GM, CFU-Meg, and BFU-E cultured from RLV-infected marrow or spleen cells was reduced. These results further demonstrate interleukin-1 and lithium are effective in modulating the toxic action of AZT on hematopoietic progenitors and that RLV-infected animals serve as a useful viral model system to study the effect of agents capable of modulating hematopoiesis in the presence of the anti-viral drug AZT. PMID- 1940612 TI - Histochemical and immunochemical study of the fate of Candida albicans inside human neutrophil phagolysosomes. AB - To further define the ultrastructural events associated with the killing of Candida albicans by human neutrophils, four methods were used: (1) the periodate thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining of vicinal-glycol containing complex carbohydrates; (2) the localization of thermostable immunodeterminants of the yeast cell wall, mannans or mannoproteins, using monospecific antibodies and a protein A-gold complex (monAb-gold); (3) the localization of mannose residues with concanavalin A labeled with gold particles (Con A-gold); (4) the localization of chitin oligomers using wheat germ agglutinin and ovomucoid labeled with gold particles (WGA-gold). The mannan-rich cell wall layers were progressively lost as shown by altered PA-TCH-SP reactivity and a diffuse pattern of staining with Con A-gold and monAb-gold. The de novo appearance of conspicuous amounts of glycogen-like particles near the plasmalemma and in the cell wall was interpreted as evidence of a reparative process of the yeast cell wall. Chitin was seemingly unaltered and readily demonstrated by the WGA-gold in the wall remnants of ghost cells. PMID- 1940613 TI - Induction of tumor necrosis factor and macrophage-mediated cytotoxicity by horseradish peroxidase and other glycosylated proteins: the role of enzymatic activity and LPS. AB - Recent studies by these investigators have shown that horseradish peroxidase (HRP) can cause murine thioglycollate-induced peritoneal macrophages (M phi) to produce both tumor necrosis factor (TNF) and enhance macrophage-mediated cytotoxicity (MMC) to 3T12 target cells. The present study identifies the roles of both enzymatic activity and contaminating lipopolysaccharides (LPS) (less than or equal to 1 ng) on these activities. The addition of 100 ng/ml of polymyxin B (PB) to enzymatically active HRP significantly reduced TNF production but did not affect MMC. Enzymatically inactive HRP (DHRP) was more effective than HRP in both TNF production and MMC but was not affected by PB. The inability of PB to modify DHRP-induced TNF suggests that LPS was not required. The induction of TNF and MMC in the absence of LPS was also corroborated by similar studies using M phi from endotoxin-resistant C3H/HeJ mice. Glycosylated proteins such as HRP, DHRP, and mannosylated bovine serum albumin (M-BSA) are known to bind to mannose receptors (mannosyl-fucosyl receptor [MFR]) on the surface of M phi. In the present studies, M-BSA behaved similarly to DHRP in that it induced both TNF secretion and MMC. These results suggest that binding to the MFR may be sufficient to induce TNF secretion and MMC. In addition, the data suggest that neither enzymatic activity nor LPS was required for DHRP-induced TNF. PMID- 1940614 TI - Cryopreserved cytoplasts from human neutrophils migrate across monolayers of human endothelial cells in response to a chemoattractant gradient. AB - We have measured the capacity of two types of granule-poor anucleate cytoplasmic fragments (cytoplasts) from human polymorphonuclear leukocytes (PMN) to migrate across the barrier imposed by monolayers of human umbilical vein endothelial cells (EC) with and without chemotactic stimulation by fMLP. Cytoplasts were made by brief heating of PMN attached to surfaces (CKP) or by discontinuous gradient centrifugation (U-CYT). In the absence of chemoattractant, both types of cytoplast adhered poorly to endothelial cell monolayers, as did unstimulated intact PMN from which the cytoplasts were derived. In the presence of a transendothelial chemoattractant gradient both types of cytoplast exhibited a marked increase in adherence to, and migration across, endothelial monolayers; CKP did so to the same extent as chemoattractant-stimulated intact PMN. Since these motile cytoplasts are markedly deficient in most cytoplasmic organelles they may serve as useful tools for the dissection of cellular mechanisms that mediate PMN migration across endothelia. PMID- 1940616 TI - ApoB-54.8, a truncated apolipoprotein found primarily in VLDL, is associated with a nonsense mutation in the apoB gene and hypobetalipoproteinemia. AB - A new, large kindred with hypobetalipoproteinemia and a previously undescribed truncated form of apolipoprotein B (apoB) has been identified. The asymptomatic, Caucasian male proband (CK, aged 37 years) has total plasma cholesterol, triglyceride, low density lipoprotein-(LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and apoB concentrations of 108, 131, 32, 50, and 16 mg/dl, respectively. Plasma samples of 11 family members spanning three generations, which had less than 5th percentile concentrations of LDL-cholesterol, contained three apoB bands detected on immunoblots: the normal apoB-100 and apoB-48 and an unusual band of apparent molecular mass of 299,356 +/- 9580 daltons (approximately 54% the molecular weight of apoB-100). Additional immunoblotting experiments using several different anti-apoB monoclonal antibodies showed that the carboxyl terminal of apoB-100 had been deleted somewhere between amino acid residues 2148-2488. A segment of genomic DNA from the proband was amplified by polymerase chain reaction (PCR) between nucleotides 7491-7791 of Exon 26 of the apoB gene. The DNA segment was cloned into pGEM3Zf(-) and sequenced. A C----T transition was found at nucleotide 7665, resulting in a premature stop codon at amino acid residue 2486 corresponding to apoB-54.8. These results were confirmed by direct sequencing of PCR products from three apoB-54.8 positive and three apoB 54.8 negative kindred members. Allele-specific oligonucleotides were used to identify other affected family members. Cosegregation of apoB-54.8 with the C--- T transition occurred in all cases. Based on haplotypes constructed from restriction fragment length polymorphism, variable number of tandem repeats, and 5' insertion/deletion analyses and from the presence or absence of apoB-54.8, it was possible to assign a single allele of apoB to the mutation throughout the family. In contrast with other shorter truncations such as apoB-31, apoB-40, and apoB-46, which are found with particles in the HDL density range, and apoB-89 that is found primarily with LDL, apoB-54.8 was found primarily in very low density lipoproteins, much less in LDL, and was virtually absent in HDL. This suggests that the length of the truncation may significantly affect the metabolism of the associated lipoprotein particles. PMID- 1940615 TI - Role of antibody-dependent cellular cytotoxicity and lymphokine-activated killer cells in AIDS and related diseases. AB - This overview summarizes current knowledge on the overall efficacy and potential contribution of antibody-dependent cellular cytotoxicity (ADCC) and lymphokine activated killer cell (LAK) activities in evoking non-major histocompatibility complex (non-MHC) cytolytic responses to human immunodeficiency virus-1 (HIV-1) infected targets. High titers of ADCC antibodies to the HIV-1 virion are present in HIV-1-seropositive populations at all stages of disease. These antibodies are broadly reactive with a large number of HIV-1 strains and are predominantly directed against envelope determinants spanning both gp120 and gp41. However, the relative ability of natural killer (NK) effectors, derived from HIV-seropositive individuals, to evoke ADCC responses becomes increasingly impaired with disease progression. HIV-1-seropositive individuals also show marked decreases in both production of and responsiveness to interleukin-2 (IL-2). HIV-1-seropositive individuals generally have the ability to generate ex vivo propagated LAK cells; however, these cytolytic effectors are less effective than their counterparts derived from healthy controls. Increased understanding and control of non-MHC restricted cytotoxic-responses to HIV, and their induction by lymphokines, may lead to improved treatment strategies for the management of AIDS and related diseases. PMID- 1940618 TI - Use of an unsaturated fatty acid auxotroph of Saccharomyces cerevisiae to modify the lipid composition and function of mitochondrial membranes. AB - KD115 (ol1), an unsaturated fatty acid auxotroph of S. cerevisiae, was grown in a semi-synthetic medium supplemented with 3.3 x 10(-4) M palmitoleic (cis 16:1) or palmitelaidic (trans 16:1) acids. The parent strain S288C was studied as a control. The lipid composition (fatty acids, neutral lipids, and phospholipids), respiratory activity (O2 consumption), and ultrastructure were compared in mutant yeast grown with each unsaturated fatty acid supplement. The fatty acid supplement represented 70-80% of the yeast fatty acids. Yeast grown in trans 16:1 contained more squalene, a higher ratio of phosphatidylethanolamine (PE) to phosphatidylcholine (PC), and had 10-20% of the respiratory activity compared to the same yeast grown in cis 16:1. The mitochondrial morphology of yeast in each growth supplement was notably different. The use of mixtures of cis and trans 16:1 in different proportions revealed that the PE/PC ratio, the squalene content, the respiratory defect, and the mitochondrial morphology were all similarly dependent on the fraction of trans 16:1 in the mixtures. As little as 10-20% of cis 16:1 in the mixture was sufficient to abrogate the physiological effects of trans 16:1 on each of the parameters noted above. The combined effects of high content of trans unsaturated fatty acid and the altered phospholipid composition seem to account for the decrease in lipid fluidity, the defective structure and function of the mitochondrial membrane. PMID- 1940617 TI - Lipoproteins in pinnipeds: analysis of a high molecular weight form of apolipoprotein E. AB - We have examined the apolipoprotein content of the lipoproteins of several marine mammals by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Their apolipoprotein (apo) B-100, apoB-48, and apoA-I migrated to virtually the same position as the comparable human apolipoproteins. In cetaceans (bottlenose dolphins and killer whales), the molecular mass of the apoE was identical to that of human apoE (35 kDa). In contrast, in the lipoproteins of pinnipeds (harbor seals, sea lions, and walrus) there was no protein comparable in size to human apoE; however, there were two proteins in the 40- to 44-kDa range. The protein with the higher apparent molecular weight (44 kDa) was apoA-IV, as determined by NH2-terminal amino acid sequencing. Sequencing of the NH2-terminal 15 amino acids of the lower molecular weight protein (40-42 kDa) revealed no obvious homology with human apoE. However, a human apoE-specific monoclonal antibody, 1D7, bound to the 40- to 42-kDa protein, allowing us to identify that protein as apoE. Sequencing of sea lion apoE cDNA clones demonstrated that sea lion apoE is 311 amino acids in length, 12 residues longer than human apoE. All 12 additional residues are located in the NH2-terminal 31 amino acids, a region that has extremely low homology with the NH2-terminal portion of human apoE. The remainder of the sea lion apoE sequence is 74% homologous to human apoE. The sea lion apoE cDNA was expressed in Chinese hamster ovary (CHO) cells as well as CHO ldlD cells, a cell line that is deficient in O-glycosylation of proteins. The size of the sea lion apoE secreted by these two cell lines, compared with the apoE in sea lion plasma, indicated that the predominant form of apoE in sea lion plasma must be posttranslationally modified. Thus, our studies have demonstrated that the higher apparent molecular weight of pinniped (sea lion) apoE is due to a longer polypeptide chain as well as posttranslational modification of the protein. PMID- 1940619 TI - Measurement of in vivo cholesterol synthesis from 2H2O: a rapid procedure for the isolation, combustion, and isotopic assay of erythrocyte cholesterol. AB - A rapid preparative scale purification of erythrocyte free cholesterol has been developed for measurements of in vivo cholesterol synthesis from 2H2O. The quantity and purity of cholesterol obtained is suitable for combustion, zinc reduction of the water formed, and determination of deuterium isotopic content by gas isotope ratio mass spectrometry. The ability to detect and to quantitate a range of cholesterol synthesis rates is illustrated by measurements on young pigs receiving diets without and with added dietary cholesterol. PMID- 1940620 TI - Quantitation of plasma mevalonic acid using gas chromatography-electron capture mass spectrometry. AB - Circulating concentrations of mevalonic acid (MVA) change in parallel with, and may be used as a marker of cholesterol biosynthesis. Plasma MVA levels have been quantified using a sensitive and specific capillary gas chromatography-electron capture mass spectrometric assay. The detection limit for MVA in plasma is 100 pg/ml; the intra-assay variation is 5.11%; the inter-assay variation is 7.7%. Using this assay, the mean plasma MVA in 15 normolipidemic subjects was 2.37 +/- 1.2 ng/ml (range 0.41-5.31 ng/ml). Administration of 40 mg of simvastatin (an HMG CoA reductase inhibitor) significantly accenutated the diurnal decrease in plasma MVA levels. This assay may be useful in investigating cholesterol synthesis rates in different dyslipidemias and individual responses of HMG-CoA reductase inhibiting drugs. PMID- 1940621 TI - Induction of fatty liver by fasting in suncus. AB - We found that a fatty liver was easily induced in a novel experimental animal, Suncus murinus (suncus), by withholding food. Hepatic triglyceride content increased linearly for up to 24 h after fasting in these animals. Serum levels of neutral lipids are very low in the fed state compared with those in rats, and decreased significantly after 24 h fasting. On the other hand, serum free fatty acids, which are at the same level in fed animals as in rats, increased threefold in the fasting suncus. In order to learn whether the fatty liver induced by fasting is an unusual physiological state or a pathological on-going state in suncus, they were refed after 24 h fasting. Refeeding resulted in a decrease in hepatic triglyceride content to the level of fed animals. Serum lipid levels, which decreased with fasting, returned to those of fed animals. This evidence indicates that hepatic lipid secretion is impaired even in a physiological state to some extent and that starvation causes increasing influx of free fatty acid to the liver, which might be followed by esterification and result in triglyceride accumulation in the liver. In conclusion, hepatic lipid and lipoprotein metabolism is unique to the suncus, which is a useful animal model for the study of intra-hepatic lipid transport. PMID- 1940622 TI - Lanosterol 14 alpha-demethylase (P45014DM): effects of P45014DM inhibitors on sterol biosynthesis downstream of lanosterol. AB - Lanosterol 14 alpha-demethylase (P45014DM) is the cytochrome P450 enzyme complex responsible for an early step in cholesterol biosynthesis, namely the 14 alpha demethylation of lanosterol. We have synthesized a novel series of steroidal substrate analogues, designed to be specific and potent inhibitors of P45014DM. We describe here the effects of these compounds on sterol biosynthesis downstream from lanosterol, focusing ultimately on their efficacy as inhibitors of cholesterol biosynthesis. Results using a radio-high performance liquid chromatography (HPLC) assay show that in rat liver microsomal preparations, with [24,25-3H]dihydrolanosterol as substrate, the compounds do indeed inhibit the biosynthesis of sterols downstream from lanosterol. A range of inhibitory potencies was observed, and the key enzyme being inhibited was believed to be P45014DM. Inhibitor efficacy was readily correlated with non-metabolized [24,25 3H]dihydrolanosterol, formation of 4,4-dimethyl-cholest-8-en-3 beta-ol, and formation of lathosterol, a sterol believed to be an excellent indicator of whole body cholesterol biosynthesis in humans. PMID- 1940623 TI - Size transformations of intermediate and low density lipoproteins induced by unesterified fatty acids. AB - Plasma from individual human subjects is known to contain multiple discrete subpopulations of low (LDL) and intermediate (IDL) density lipoproteins that differ in particle size and density. The metabolic origins of these subpopulations are unknown. Transformation of IDL and larger LDL to smaller, denser LDL particles had been postulated to occur as a result of the combined effects of triglyceride hydrolysis and lipid transfer. However, the presence of multiple small LDL subspecies has been described in patients lacking cholesteryl ester transfer protein. We have characterized an alternative pathway in which size decrements in IDL or LDL are produced in the presence of unesterified fatty acids and a source of apolipoprotein (apo) A-I. Incubation of IDL or LDL subfractions with palmitic acid and either high density lipoproteins (HDL), apoHDL, or purified apoA-I gives rise to apoA-I, apoB-containing complexes that can dissociate into two particles, an apoB-containing lipoprotein with particle diameter 10-30 A smaller than the starting material, and a still smaller species (apparent peak particle diameter 140-190 A) containing lipid and apoA-I but no apoB. The newly formed IDL or LDL are depleted in phospholipid and free cholesterol with no change in apoB-100 as assessed by SDS gel electrophoresis. We hypothesize that this reaction may contribute to the formation of discrete IDL and LDL subpopulations of varying size during the course of hydrolysis of triglyceride-rich lipoproteins in plasma. PMID- 1940624 TI - Dissociation of high density lipoprotein precursors from apolipoprotein B containing lipoproteins in the presence of unesterified fatty acids and a source of apolipoprotein A-I. AB - Incubation of low (LDL), intermediate (IDL), or very low density lipoproteins (VLDL) with palmitic acid and either high density lipoproteins (HDL), delipidated HDL, or purified apolipoprotein (apo) A-I resulted in the formation of lipoprotein particles with discoidal structure and mean particle diameters ranging from 146 to 254 A by electron microscopy. Discs produced from IDL or LDL averaged 26% protein, 42% phospholipid, 5% cholesteryl esters, 24% free cholesterol, and 3% triglycerides; preparations derived from VLDL contained up to 21% triglycerides. ApoA-I was the predominant protein present, with smaller amounts of apoA-II. Crosslinking studies of discs derived from LDL or IDL indicated the presence of four apoA-I molecules per particle, while those derived from large VLDL varied more in size and contained as many as six apoA-I molecules per particle. Incubation of discs derived from IDL or LDL with purified lecithin:cholesterol acyltransferase (LCAT), albumin, and a source of free cholesterol produced core-containing particles with size and composition similar to HDL2b. VLDL-derived discs behaved similarly, although the HDL products were somewhat larger and more variable in size. When discs were incubated with plasma d greater than 1.21 g/ml fraction rather than LCAT, core-containing particles in the size range of normal HDL2a and HDL3a were also produced. A variety of other purified free fatty acids were shown to promote disc formation. In addition, some mono and polyunsaturated fatty acids facilitated the formation of smaller, spherical particles in the size range of HDL3c. Both discoidal and small spherical apoA-I-containing lipoproteins were generated when native VLDL was incubated with lipoprotein lipase in the presence of delipidated HDL. We conclude that lipolysis product-mediated dissociation of lipid-apoA-I complexes from VLDL, IDL, or LDL may be a mechanism for formation of HDL subclasses during lipolysis, and that the availability of different lipids may influence the type of HDL precursors formed by this mechanism. PMID- 1940625 TI - Effects of pravastatin and cholestyramine on products of the mevalonate pathway in familial hypercholesterolemia. AB - Patients with heterozygous familial hypercholesterolemia (n = 12) were treated either with pravastatin, a specific inhibitor of HMG-CoA reductase, or cholestyramine, followed by a period of combined treatment with both drugs. Initially, these patients had increased serum levels of low density lipoprotein (LDL) cholesterol (8.77 +/- 0.48 mmol/l; SEM), lathosterol (5.32 +/- 0.60 mg/l), and ubiquinone (0.76 +/- 0.09 mg/l), while the serum dolichol concentration was in the normal range. Cholestyramine treatment (n = 6) decreased the levels of LDL cholesterol (-32%) and increased lathosterol (+125%), but did not change dolichol or ubiquinone levels in a significant manner. Pravastatin treatment (n = 6) decreased LDL cholesterol (-27%), lathosterol (-46%), and ubiquinone (-29%). In this case, the amount of dolichol in serum also showed a small but statistically insignificant decrease (-16%) after 12 weeks of treatment. Combined treatment with cholestyramine and pravastatin (n = 6) resulted in changes that were similar to, but less pronounced than, those observed during pravastatin treatment alone. In no case was the ratio between ubiquinone and LDL cholesterol reduced. Possible effects on hepatic cholesterol, ubiquinone, and dolichol concentrations were studied in untreated (n = 2), cholestyramine-treated (n = 2), and pravastatin treated (n = 4) gallstone patients and no consistent changes could be observed. The results indicate that treatment with pravastatin in familial hypercholesterolemia decreases serum ubiquinone levels in proportion to the reduction in LDL cholesterol. PMID- 1940627 TI - Altered ultrastructural morphology of self-aggregated low density lipoproteins: coalescence of lipid domains forming droplets and vesicles. AB - Lipid droplets and vesicles can presumably be formed directly from lipoproteins in the extracellular space in atherosclerosis, but an in vitro demonstration of the phenomenon in the absence of cellular pathways has been lacking. Low density lipoproteins (LDL) are known to undergo self-aggregation after brief vortexing in vitro. In the present study, LDL aggregates were examined by electron microscopy, using new mordant techniques for lipid visualization, and by chemical analysis. Aggregation of LDL by vortexing is regularly accompanied by the formation of comparatively large lipid droplets (up to 600 nm diameter) and vesicles. Aggregates containing droplets and vesicles were formed after as little as 5 sec of vortexing, and LDL protein and cholesteryl ester were almost completely (95%) incorporated into aggregates after 4 min vortexing. Substantial fractions of phospholipid and unesterified cholesterol from the original LDL remained in solution even after 4 min vortexing, forming large multilamellar vesicles that did not adhere to the aggregated material. Spontaneous aggregates retrieved from LDL solutions after prolonged storage were also examined by electron microscopy, revealing similar lipid droplets and vesicles. The ultrastructural appearance of LDL aggregated in vitro is remarkably similar to the appearance of extracellular lipid deposits in atherosclerosis, lending credence to the hypothesis of direct extracellular formation of these deposits from lipoproteins. PMID- 1940626 TI - Regulation of hepatic apolipoprotein synthesis in the 17 alpha-ethinyl estradiol treated rat. AB - Regulatory mechanisms of hepatic apolipoprotein synthesis were studied in groups of male Sprague-Dawley rats made severely hypolipidemic by treatment with pharmacological doses of 17 alpha-ethinyl estradiol. Treatment resulted in a marked reduction of plasma cholesterol and apolipoproteins B, A-I, and A-IV. Hepatic apoA-I mRNA and apoA-I synthesis were increased in the ethinyl estradiol treated animals. Hepatic apoA-IV protein synthesis rates were unaltered; however, a reduction of the apoA-IV mRNA level was observed. Diet-control studies suggested the effects of 17 alpha-ethinyl estradiol on apoA-I, unlike those on apoA-IV, appeared to be related to the steroid and not to reduced caloric intake. Livers of control and ethinyl estradiol-treated rats synthesized both apoBH and apoBL. Total hepatic apoB (apoBL plus apoBH) synthesis and apoB mRNA levels in the ethinyl estradiol-treated rats were similar to ad libitum fed or diet controls. In ad libitum fed and diet-control rats, 21% and 32%, respectively, of newly synthesized hepatic apoB was apoBH. In contrast, 47% of the newly synthesized apoB in the ethinyl estradiol-treated animal was apoBH. Nucleotide sequence analysis of hepatic apoB mRNA confirmed a marked decrease in the proportion of the apoBL mRNA in ethinyl estradiol-treated animals. After cessation of 17 alpha-ethinyl estradiol treatment, the hepatic apolipoprotein A-I synthesis rate, apolipoprotein A-I and A-IV mRNA levels, and the apoBH and apoBL synthesis rates, as well as plasma apolipoprotein and cholesterol levels, returned to normal. A major finding of the present study is that pharmacological doses of ethinyl estradiol do not affect total hepatic apoB synthesis, but increase the relative amount of apoBH synthesized. PMID- 1940628 TI - Expression of rat hepatic lipase in heterologous systems: evidence for different sites for interface binding and catalysis. AB - Rat hepatic triglyceride lipase was expressed as a bacterial fusion protein and as a secreted protein in eukaryotic cells. The bacterial fusion construct coded for seven amino acids at the N-terminus which are not present in the hepatic lipase cDNA, but otherwise consisted of only the complete mature lipase sequence. Fusion protein was isolated as an insoluble product which did not have lipase or phospholipase activities; it was, however, active as an esterase when solubilized after preparative gel electrophoresis. The fusion protein was used to raise polyclonal antibodies that recognize native rat hepatic lipase and inhibit its activity. For eukaryotic expression, a full-length rat hepatic lipase cDNA clone was inserted into the metallothionein promoter expression vector pMTSV40polyA.Bam. Transfected CHO cells, induced with ZnSO4, secreted an immunoreactive protein of Mr approximately 57,000. A lipase-producing clonal cell line was isolated and used to characterize the enzyme. The protein was purified from serum-free medium by heparin-Sepharose and DEAE-Trisacryl M column chromatography. It was apparently identical to native rat hepatic lipase, with the exception of the conformation of the linkage of the sialic acids which form part of the N-linked carbohydrate complexes. The bacterial fusion protein, the CHO-produced lipase, and native rat hepatic lipase were all inhibited by phenylmethylsulfonyl fluoride, implying that they function catalytically as serine esterases. Substrate competition studies indicated that the esterase and lipase activities use the same active site; thus, the major defect in the fusion protein was probably in triglyceride substrate binding. These results suggest that interface binding and catalysis occur at different sites in the protein. PMID- 1940629 TI - Selective reduction of oxo bile acids: synthesis of 3 beta-, 7 beta-, and 12 beta hydroxy bile acids. AB - Preparation of some biologically important keto bile acids is described. Advantage is taken of the preferential ketalization of 3-oxo group in bile acids over 7- and 12-oxo groups for the selective reduction of these keto groups. The method was found to be specially useful for preparation of 7 beta-, 12 alpha, and 12 beta-[3H]-3-oxo bile acids. Improved methods are also described for the preparation of epimers of naturally occurring bile acids at C-3, C-7, and C-12. 3 beta-Hydroxy bile acids (iso-bile acids) were prepared with the use of diethylazodicarboxylate/triphenylphosphine/formic acid. Iso-bile acids were obtained in excellent yields (80-95%) except during synthesis of isoursodeoxycholic acid (yield, 50%). Isoursodeoxycholic acid was, however, prepared in very good yield via epimerization of 3 alpha-hydroxyl group in 7 oxolithocholic acid followed by stereoselective reduction of 7-oxo group. A highly efficient method for the reduction of 7-oxo and 12-oxo groups was developed. Thus, 7-oxolithocholic acid and 7-oxoisolithocholic acid on reduction with potassium/tertiary amyl alcohol yielded ursodeoxycholic acid and isoursodeoxycholic acid in yields of 96% and 94%, respectively, while reduction of 7-oxodeoxycholic acid resulted in ursocholic acid in 93% yield. In a similar manner, reduction of 12-oxolithocholic acid and 12-oxochenodeoxycholic acid yielded 3 alpha, 12 beta-dihydroxy-5 beta-cholanoic acid (lagodeoxycholic acid; 92% yield) and 3 alpha, 7 alpha, 12 beta-trihydroxy-5 beta-cholanoic acid (lagocholic acid, 86% yield). PMID- 1940630 TI - Utilization of different fatty acids for hepatic and biliary phosphatidylcholine formation and the effect of changes in phosphatidylcholine molecular species on biliary lipid secretion. AB - Biliary cholesterol secretion is ordinarily tightly coupled to phosphatidylcholine (PC) secretion. Bile PCs are distinct in composition and predominantly composed of molecular species with 16:0 in the sn-1 position and 18:2 and 18:1 in the sn-2 position. In an attempt to acutely change the composition of biliary PCs and to assess the effect of a change in PCs on biliary cholesterol secretion, isolated livers were perfused with a variety of single free fatty acids. Rat livers with bile duct cannulas were perfused with a recirculating medium, taurocholate (40 mumol/h), and albumin-bound 16:1, 17:1, 18:1, 20:1, 18:2, 20:4, or 20:5 fatty acids (90 mumol/h) for 2 h. Biliary lipid secretion was measured and bile and liver PC compositions were compared at the start and end of perfusion. Results showed 1) greater utilization of shorter chain than longer chain fatty acids for bile PC formation (16:1 greater than 17:1 greater than 18:2 or 18:1 greater than 20:5, 20:4 or 20:1); 2) no similar pattern of FA utilization for liver PC formation; 3) preferentially greater incorporation of fatty acids into bile PCs compared to liver PCs when perfused fatty acids were used for esterification at both sn-1 and sn-2 positions of PC (to form diunsaturated PCs); and 4) increased biliary secretion of cholesterol relative to PC only when the population of PCs that was newly formed included more hydrophilic molecular species of PC than are present in native bile (that was observed only with perfusion of 16:1). Changes in biliary PC secretion or cholesterol/PC secretion occurred independently of any change in bile salt secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940631 TI - Incorporation of a stable isotopically labeled amino acid into multiple human apolipoproteins. AB - Procedures are presented for the separation and determination of the isotopic enrichment of multiple human apolipoproteins labeled in vivo with a stable isotope amino acid. The isotopic enrichments of plasma lysine and plasma apolipoproteins were monitored for 16 days after a single intravenous dose of [4,4,5,5-2H4]lysine (5 mg/kg body weight). The use of a multiply deuterated amino acid enabled the measurement of isotopic enrichments above background over the entire 16-day time course in all proteins. Individual apolipoproteins were separated on a specially designed gradient sodium dodecyl sulfate polyacrylamide gel electrophoresis system cast in a conventional slab gel apparatus which resolved apoB-100, apoE, apoA-I, apoA-II, apoC-I, apoC-II, apoC-III-1, and apoC III-2 on a single gel. After staining with Coomassie blue, proteins bands (containing 5 to 30 micrograms of individual apolipoprotein) were excised from the gel. Amino acids were recovered from hydrolyzed gel slices, derivatized, and analyzed by gas chromatography-mass spectrometry for determination of lysine isotopic enrichments. The utility of the method is demonstrated using examples of apolipoproteins B-100, A-I, A-II, C-I, C-II, and C-III from either total plasma d less than 1.21 g/ml lipoproteins or selected lipoprotein subfractions. Lysine isotopic enrichments of proteins were generally determined with a precision of better than 5%. The isotopic enrichment profiles were consistent with literature reports of apolipoprotein metabolic kinetics based on the use of radioiodinated apolipoproteins. The procedures outlined can be used to separate and measure the isotopic enrichment of virtually any apolipoprotein from any chosen lipoprotein fraction. Thus, these procedures should find wide application in the study of apolipoprotein metabolic kinetics. PMID- 1940632 TI - Mechanism of the HDL2 stimulation of progesterone secretion in cultured placental trophoblast. AB - Lipoprotein cholesterol (C) supports the high rate of progesterone production by the human placenta as endogenous cholesterol synthesis is low. To study underlying mechanisms whereby lipoproteins, including high density lipoprotein-2 (HDL2), stimulate progesterone secretion, trophoblast cells were isolated from human term placentas and maintained in primary tissue culture. Lipoproteins were added at several concentrations and medium progesterone secretion was determined. HDL2 (d 1.063-1.125 g/ml) as well as low density lipoproteins (LDL) (d 1.019 1.063 g/ml) but not HDL3 (d 1.125-1.21 g/ml) stimulated progesterone secretion in a dose-dependent manner, with HDL2 cholesterol entering the cell and serving as substrate for progesterone synthesis. Conversely, LDL and HDL2 produced a significant decrease in [2-14C]acetate incorporation into cell cholesterol. Cholesterol-depleted lipoproteins did not stimulate progesterone secretion. The stimulating effect of LDL was abolished by apolipoprotein modification by cyclohexanedione or reductive methylation and by the addition of anti-LDL receptor antibody or 10 microM chloroquine to the medium. [14C]acetate conversion into cholesterol was accelerated by these procedures. However, HDL2 stimulation of progesterone secretion and reduction of [14C]acetate incorporation into cholesterol was not blocked by chemical modification of apolipoproteins, anti-LDL receptor antibody, or chloroquine. Treatment of HDL2 with tetranitromethane or dimethylsuberimidate also did not block the stimulation of progesterone. To determine whether the capacity of HDL2 to deliver cholesterol to the trophoblast cells was restricted to subfractions differing in apoE content, HDL2 was chromatographed on heparin-Sepharose and three fractions (A, B, and C) were obtained. Fraction A was poorest in apoE and free cholesterol, fraction B contained the majority of cholesterol, and fraction C was the richest in apoE and free cholesterol. When added to trophoblast cells, fraction A stimulated little progesterone secretion, fraction B stimulated moderately, and fraction C did so greatly. Modification of these subfractions with cyclohexanedione or reductive methylation did not inhibit these effects. In conclusion, HDL2 stimulated progesterone secretion in human trophoblast cell culture. Contrary to LDL, the HDL effect was not mediated by apolipoproteins or the LDL receptor pathway. The ability of HDL2 to stimulate progesterone secretion is consistent with the passive transfer of free cholesterol to the cell membrane from a physicochemically specific subfraction of HDL. This mechanism may be an auxiliary source of cholesterol for human steroidogenic cells. PMID- 1940634 TI - De novo production of low density lipoproteins: fact or fancy. AB - Many investigators, observing an apparent dilution in the plasma specific activity (SA) of apolipoprotein B-100 (apoB) in low density lipoprotein (LDL) as compared with that in very low density lipoprotein (VLDL) after injection of radiolabeled VLDL, have formulated kinetic hypotheses incorporating the concept of de novo production of LDL to explain their data in humans and other mammals. These hypotheses, with rare exception, do not account for the kinetic heterogeneity known to exist in the apoB of human VLDL on the basis of size and in the apoB of rabbit VLDL on the basis of size and presence of apolipoprotein E. When a logical analysis of such kinetic heterogeneity of apoB in plasma VLDL is performed, it becomes clear that the apparent dilution of the SA of apoB in LDL relative to that in VLDL can be explained without the requirement for de novo production of LDL. Although this alternative hypothesis, incorporating the concept of kinetic heterogeneity of apoB in VLDL, does not exclude the process of de novo production of LDL, which so many investigators have invoked to explain their data, it does raise a question as to the existence of such a process since an alternative hypothesis can explain such data just as well. Clearly, more experimental data on the kinetic heterogeneity of human and other mammalian VLDL are needed before a reasonable choice can be made between these two hypotheses. PMID- 1940633 TI - Control of variance in experimental studies of hyperlipidemia using the WHHL rabbit. AB - Between-animal variability has frustrated many experimental studies in outbred animal models of human disease. Variability that arises from genetic heterozygosity can be minimized by use of experimental designs that match littermates (polyzygotic twins) across control and treatment groups. Poor breeding vigor has prevented use of this experimental design in the WHHL rabbit model of hyperlipidemia and atherosclerosis. A comparison of reproduction in WHHL and normal rabbits demonstrated that litter size is limited by functional deficits at ovulation, implantation, and gestation in WHHL females. Superovulation of females reliably produced expanded litters of WHHL rabbits. Plasma lipids were measured in expanded litters of Japanese White WHHL (JW-WW) and English Half-lop WHHL (EHL-WW) rabbits. The variance of plasma cholesterol within sibships was two- to three-fold less than that between-litters. Intraclass correlation of total cholesterol within litters of EHL-WW was 0.72 and within litters of JW-WW was 0.67. These data provide evidence of genetic modulation of hypercholesterolemia in WHHL rabbits and demonstrate that experimental designs in which littermates are paired across groups can decrease the number of animals needed or increase the sensitivity of hypothesis tests by two- to threefold. PMID- 1940635 TI - Activated platelets secrete a protein-like factor that stimulates oxidized-LDL receptor activity in macrophages. AB - Platelet secretory products were shown to modulate the interaction between lipoproteins and their receptors on macrophages. Preincubation of macrophages for 2 h at 37 degrees C with platelet conditioned medium (PCM), followed by its removal and a further 5-h incubation in the presence of oxidized-LDL (Ox-LDL), resulted in increased cellular degradation of Ox-LDL (34%), stimulation of cellular cholesterol esterification (31%), and mass accumulation of esterified and nonesterified cholesterol (25% and 41%, respectively). These effects were found to be the result of a PCM-mediated increase in the number of Ox-LDL receptors on macrophages. PCM was shown to interact with the macrophage scavenger receptor. Enhanced Ox-LDL uptake by macrophages preincubated with PCM could not be reproduced when PCM remained in the incubation medium. Maintenance of PCM in the incubation medium reduced Ox-LDL uptake by macrophages (40%) and was shown to be PCM dose-dependent. Whereas incubation at 37 degrees C demonstrated enhanced uptake of Ox-LDL, preincubation of macrophages with PCM at 4 degrees C exhibited a 64% reduction in Ox-LDL-mediated cellular cholesterol esterification. Thus, PCM internalization by macrophages after its binding to the scavenger receptor is required to promote the enhancing effect of PCM on Ox-LDL uptake by macrophages. PCM activity was associated with platelet degranulation, and was recovered in the protein fraction of PCM. It was found to be heat- and trypsin-labile with a molecular weight greater than 25,000. PCM obtained from platelets derived from a patient with alpha granules deficiency failed to enhance the uptake of Ox-LDL by macrophages, suggesting that the active protein-like factor in PCM originated from platelet alpha granules. These results indicate that a platelet-secreted protein-like factor can modulate macrophage uptake of Ox-LDL with subsequent effect on foam cell formation. PMID- 1940636 TI - Beta-VLDL increases endothelial cell plasma membrane cholesterol. AB - In this study, the distribution of free cholesterol in cholesterol-loaded endothelial cells was examined. For these studies, cell fractionation methods were used to assess marker enzyme activity and cholesterol distribution. Treatment of rabbit aortic endothelial cells for 3 days with 50 micrograms/ml of beta-very low density lipoprotein (beta-VLDL) or malondialdehyde-low density lipoprotein (MDA-LDL) but not LDL caused a 50-100% increase in total cell unesterified cholesterol. The accumulation of free rather than esterified cholesterol in endothelial cells may be due to the ratio of hydrolysis to esterification, which we have shown in this study to be 10-fold higher in endothelial cells than in smooth muscle cells. This free cholesterol is found in the fractions enriched in plasma membrane markers and, to a lesser extent, in the Golgi-enriched fractions. The amount of cholesterol per mg of protein was increased approximately 50% in these fractions from cells treated for 3 days with 50 micrograms/ml of beta-VLDL. These increases in cholesterol content were reversible upon incubation of cells for 3 days in medium containing 15% fetal bovine serum. Alterations in several membrane functions were also observed in cholesterol-loaded cells. The activity of alkaline phosphatase, an enzyme marker for plasma membranes, was decreased by 25% and an alteration in membrane associated microfilaments was seen with phalloidin staining. This morphological change in microfilaments was reflected in a decrease in filament ends as shown by cytochalasin binding and occurred without a change in total actin or vinculin. These microfilament changes were reversible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940637 TI - Abnormal clearance of postprandial Sf 100-400 plasma lipoproteins in insulin dependent diabetes mellitus. AB - Studies were carried out in three normolipidemic non-obese men with insulin dependent diabetes mellitus (IDDM) and three normal men, to assess whether the clearance of postprandial Sf 100-400 lipoproteins is decreased in IDDM. Sf greater than 100 lipoproteins isolated from plasma 4.5 h after fat ingestion were labeled with 125I and injected into the same subject intravenously. ApoB radioactivity was measured over time in Sf greater than 400, Sf 100-400, and Sf 20-100 lipoproteins isolated from plasma and analyzed using a kinetic model that included both fast and slow delipidation cascades, where lipolysis and uptake of particles by the liver and other tissues were represented. Fractional catabolic rates of Sf 100-400 lipoproteins (min-1) were decreased in diabetic versus control subjects: fast = 0.170 +/- 0.126 versus 0.680 +/- 0.242 (mean +/- SD) (P less than 0.05, two-tailed) and slow = 0.011 +/- 0.006 versus 0.031 +/- 0.015 (P less than 0.05, one-tailed). Kinetic analysis showed that the data were consistent with decreased uptake by the tissues for the fast cascade (diabetic, 0.084 +/- 0.082, vs. control, 0.617 +/- 0.328, P less than 0.05, one-tailed). A similar trend was observed for the slow cascade. There were no significant differences between the two groups in the intraplasma lipolysis rates of Sf 100 400 particles. Analysis of the composition of the injected particles showed that they were total cholesterol (TC)- versus triglyceride (TG)-enriched (P less than 0.001, log-ratio analysis of composition) in IDDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940638 TI - Role of cholesterol synthesis in regulation of bile acid synthesis and biliary cholesterol secretion in humans. AB - We used lovastatin, a specific inhibitor of HMG-CoA reductase, to study the role of cholesterol synthesis in regulation of both bile acid synthesis, measured by release of 14CO2 from [26-14C]cholesterol, and biliary cholesterol secretion, measured by standard marked perfusion techniques, in humans. Six volunteers were studied in each of four periods: a) control; b) 6-10 hours after a single 40 mg oral dose of lovastatin to study acute effects; c) after 5-6 weeks of lovastatin 40 mg orally twice a day to study steady-state effects; and d) 24 h after cessation of chronic lovastatin. Mean bile acid synthesis fell to 69% of control (P less than 0.01) after single-dose lovastatin and remained at 83% of control after 5-6 weeks on lovastatin (P less than 0.05). After withdrawal of lovastatin, mean bile acid synthesis was 88% of control (NS). Mean biliary cholesterol secretion did not change after single-dose lovastatin (103% of control), but fell to 81% of control during chronic lovastatin treatment (P less than 0.05). After withdrawal of lovastatin, mean cholesterol secretion remained at 80% of control (P less than 0.05). These data suggest that in humans cholesterol synthesis is an immediate regulator of bile acid synthesis. Cholesterol synthesis also regulates biliary cholesterol secretion, but the effect is not immediate and therefore may be indirect. PMID- 1940639 TI - Regulation of epidermal sphingolipid synthesis by permeability barrier function. AB - A mixture of sphingolipids, cholesterol, and free fatty acids forms the intercellular membrane bilayers of the stratum corneum which are presumed to regulate epidermal barrier function. Prior studies have shown that both cholesterol and fatty acid synthesis are rapidly regulated by epidermal barrier requirements. In contrast, the importance of sphingolipids in barrier function has not been directly demonstrated. Here, we have assessed both sphingolipid synthesis by [3H]H2O incorporation and serine palmitoyl transferase (SPT) activity in relation to modulations in barrier function. Incorporation of [3H]H2O into sphingolipids increased after barrier disruption with acetone, with maximal increase (170%) occurring 5-7 h after treatment (P less than 0.005). As barrier function returned to normal over 24 h, incorporation of tritium into sphingolipids normalized. SPT activity also increased after barrier disruption, peaking at 6 h (150%) (P less than 0.05), and returning towards normal by 24 h. Artificial restoration of the barrier with a water vapor-impermeable membrane prevented the increases in both [3H]H2O incorporation into sphingolipids and enzyme activity. Finally, SPT activity was increased in two other models of barrier dysfunction, cellophane tape-stripping and essential fatty acid deficiency. Occlusion normalized SPT activity in both of these models as well. These studies: a) demonstrate a distinctive, delayed increase in epidermal sphingolipid synthesis in response to barrier requirements that contrasts with the immediate responses of cholesterol and fatty acid synthesis; and b) suggest that sphingolipids are important for the maintenance of the epidermal permeability barrier. PMID- 1940640 TI - Differential turnover of polyunsaturated fatty acids in plasmalogen and diacyl glycerophospholipids of isolated cardiac myocytes. AB - To investigate the relative turnover of esterified polyunsaturated fatty acids in diacylglycerophospholipids and plasmalogens in isolated cardiac myocytes, we characterized the phospholipid composition and distribution of radiolabel in different phospholipid classes and in individual molecular species of diradyl choline (CGP) and ethanolamine (EGP) glycerophospholipids after incubation of isolated cardiac myocytes with [3H]arachidonate or [14C]linoleate. Plasmalogens in CGP (55%) and EGP (42%) quantitatively accounted for the total plasmalogen content (39%) of cardiac myocyte phospholipids. Plasmalogens comprised 86% and 51% of total arachidonylated CGP and EGP mass, respectively, and [3H]arachidonate was primarily incorporated into plasmalogens in both CGP (65%) and EGP (61%) classes. The specificity activity of [3H]arachidonylated diacyl-CGP was approximately 2- to 5-fold greater than that of [3H]arachidonylated choline plasmalogen, whereas comparable specific activities were found in the [3H]arachidonate-labeled ethanolamine plasmalogen and diacyl-EGP pools. Of the total linoleate-containing CGP and EGP mass, 54% and 57%, respectively, was esterified to plasmalogen molecular species. However, [14C]linoleate was almost exclusively incorporated into diacyl-CGP (96%) and diacyl-EGP (86%). The specific activities of [14C]linoleate-labeled diacyl-CGP and diacyl-EGP were 5- to 20-fold greater than that of the [14C]linoleate-labeled plasmalogen pools. The differential incorporation of polyunsaturated fatty acids in plasmalogens and diacylglycerophospholipids demonstrates that the metabolism of the sn-2 fatty acyl moiety in these phospholipid subclasses is differentially regulated, possibly fulfilling separate and distinct physiologic roles. PMID- 1940641 TI - Apparent convergence (at 2-monoacylglycerol level) of phosphatidic acid and 2 monoacylglycerol pathways of synthesis of chylomicron triacylglycerols. AB - Dietary fats are converted into chylomicron triacylglycerols via the 2 monoacylglycerol and phosphatidic acid pathways of acylglycerol formation. In view of the known positional and fatty acid specificity of the acyltransferases, the triacylglycerol structures resulting from the two pathways would be expected to differ, but this has not been demonstrated. We have performed stereospecific analyses on the chylomicron triacylglycerols from rats fed menhaden oil and the corresponding fatty acid alkyl esters, which would be expected to be assimilated via the monoacylglycerol and the phosphatidic acid pathways, respectively. The results show a remarkable similarity between the two triacylglycerol types in the fatty acid composition of the sn-1 and sn-3 positions, along with marked differences in the composition of the sn-2 positions. The triacylglycerols from rats fed oil retained about 85% of the original fatty acids in the sn-2 position, including a high proportion of the long chain polyunsaturates (e.g., 5-7% 20:5 and 4-5% 22:6). The triacylglycerols from rats fed the alkyl ester contained large amounts of endogenous fatty acids in the sn-2 position (e.g., 18% 16:1, 14% 18:1, 14% 18:2, and 2.5% 20:4), which approximated the composition of the sn-2 position of the presumed phosphatidic acid intermediates. The sn-1 position contained a much higher proportion of polyunsatured fatty acids (e.g., 12-13% 20:5, 5-6% 22:6) than the sn-2 position (e.g. 2-3% 20:5, 0-0.6% 22:6) of triacylglycerols from rats fed the ester. We conclude that the chylomicron triacylglycerols arising via the 2-monoacylglycerol and the phosphatidic acid pathways differ mainly in the composition of the fatty acids in the sn-2 position. The similarity in the acids of the sn-1 and sn-3 positions of the chylomicron triacylglycerols from rats fed oil or ester is consistent with a hydrolysis of the acylglycerol products of the phosphatidic acid pathway to 2 monoacylglycerols prior to reconversion to triacylglycerols via the monoacylglycerol pathway and secretion as chylomicrons. PMID- 1940642 TI - Crystal structure of cholestanyl caprylate and binary phase behavior with cholesteryl caprylate. AB - The crystal structure of cholestanyl n-octanoate (caprylate) (C35H62O2) is monoclinic with space group A2 and cell dimensions a = 10.103(7), b = 7.646(7), c = 87.63(7) A, beta = 90.51(6) degrees; Z = 8 [two molecules (A, B) in asymmetric unit], V = 6769 A3, Dc = 1.010 g cm-3. Integrated X-ray intensities for 3798 reflections with I greater than 2 sigma (I) were measured with a rotating anode diffractometer at room temperature. The structure was determined using direct methods. Block diagonal least squares refinement gave R = 0.111. Molecules A and B have almost fully extended conformations, but differ significantly in the rotation about the ester bond and in the C17 chains. The molecular packing in the crystal structure of cholestanyl caprylate consists of stacked bilayers each having d002 = 43.8 A in thickness and within each bilayer, cholestanols pack with cholestanols and caprylate chains pack with caprylate chains. The crystal structure is very similar to that of cholesteryl myristate but is quite different from that of cholesteryl caprylate. The phase equilibria of the cholestanyl caprylate/cholesteryl caprylate binary system have been shown to involve limited mutual solubility of the two components and to have a eutectic point at 73% cholestanyl caprylate. The cholesteric mesophase is monotropic at all compositions except for a narrow range near the eutectic point where it is enantiotropic. PMID- 1940643 TI - Influence of dietary n-3 fatty acids on macrophage glycerophospholipid molecular species and peptidoleukotriene synthesis. AB - The study examined the ability of dietary n-3 fatty acids to modify mouse peritoneal macrophage glycerophospholipid molecular species and peptidoleukotriene synthesis. After a 2-week feeding period, fish versus corn oil feeding significantly (P less than 0.01) lowered n-6 polyunsaturated fatty acid (PUFA) mol % levels, i.e., arachidonic acid (20:4n-6) in diacylphosphatidylserine (PtdSer), diacylphosphatidylinositol (PtdIns), diacylglycerophosphoethanolamine (PtdEtn), alkenylacylglycerophosphoethanolamine (PlsEtn), and diacylglycerophosphocholine (PtdCho). A notable exception was alkylacylglycerophosphocholine (PakCho), where only moderate decreases in 16:0 20:4n-6 and 18:0-20:4n-6 species were observed after fish oil supplementation. The predominant n-3 PUFA in macrophage phospholipid subclasses was docosapentaenoic acid (22:5n-3). The major n-3 species were 18:0-22:5n-3 in PtdIns, PtdSer, glycerophosphoethanolamines (EtnGpl) and 16:0-22:5n-3 in PtdCho and PlsEtn. The major n-3-containing species in PakCho were 16:0-20:5n-3 and 18:1 22:6n-3. These findings indicate that n-3 PUFA are differentially incorporated into macrophage phospholipid subclasses after dietary fish oil supplementation, and suggest that phospholipid remodeling enzymes selectively discriminate between substrates based on compatibility of sn-1 covalent linkage and the composition of the sn-1 and sn-2 aliphatic chains. Macrophage peptidoleukotriene synthesis was also strongly influenced after fish oil feeding; the LTC5/LTC4 ratio was significantly higher (P less than 0.01) in fish oil-fed animals than in corn oil fed animals, 0.85 versus 0.01, respectively. These ratios were subsequently compared to phospholipid molecular species 20:5n-3/20:4n-6 ratios in order to determine potential sources of eicosanoid precursors. PMID- 1940645 TI - [Vascular manifestation of thoracic outlet syndrome. Prospective study of 104 patients]. AB - On the basis of a prospective study of 104 patients, the authors discuss the diagnostic value of the clinical symptoms revealing the thoracic outlet syndrome (TOS), as well as the specificity of the vascular functional exploration carried out to establish the diagnosis. Non-systematized pain and dysesthesia in the upper limb, with a postural or nocturnal onset, and Raynaud's sign are the most frequently observed signs. The "candlestick" maneuver still is the most reliable clinical triggering maneuver. The clinical features and the vascular functional explorations (capillaroscopy and digital plethysmography) allow demonstrating the existence of a true Raynaud's syndrome secondary to the TOS. The results of the arterial Doppler study distinguish the symptomatic and asymptomatic sides in the same patient, though without any correlation with the symptoms observed. The Doppler examination therefore seems to be reliable to demonstrate an anatomical duct, but remains insufficient to establish a causal relationship with the signal symptoms in most cases. PMID- 1940644 TI - Inhibitors of sterol synthesis. Characterization of beta,gamma-unsaturated analogs of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one and their effects on 3 hydroxy-3-methylglutaryl coenzyme A reductase activity in CHO-K1 cells. AB - Treatment of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (1), a potent regulator of cholesterol metabolism, with perchloric acid in methanol resulted in its partial isomerization to the beta,gamma-unsaturated 15-ketosterols, 3 beta hydroxy-5 alpha,14 beta-cholest-8-en-15-one (2) and 3 beta-hydroxy-5 alpha,14 beta-cholest-7-en-15-one (3), which were easily separated from 1 by chromatography. Isomers 1, 2, and 3 could be distinguished by their chromatographic retention times as well as by their physical and spectral properties. Reduction of 2 with sodium borohydride gave 5 alpha,14 beta-cholest-8 ene-3 beta,15 beta-diol (4), for which the C-15 configuration was established from the lanthanide-induced shifts of its 3 beta-tert-butyldimethylsilyl ether. 1H and 13C NMR chemical shift differences between 2, 3, and 4 indicated the involvement of variable populations of conformers that differ in the flexible C-D ring system and in the side chain. Compounds 2, 3, and 4 lowered the levels of 3 hydroxy-3-methylglutaryl coenzyme A reductase activity in CHO-K1 cells. PMID- 1940646 TI - [Self-expanding endoprostheses. Applications in iliac and femoro-popliteal arteries]. AB - Vascular endoprosthesis are aimed at optimizing the results of angioplasty. They are metallic cylinders, most often meshed, laid against the wall of the vessel and progressively incorporated into the intima by endothelial coverage. Experimental studies show that this incorporation occurs within a few weeks. The prosthesis are either self-expanding or mounted on a dilatation balloon. Their aim is to restore a good-quality caliber by smoothing the parietal irregularities that were frequently encountered after dilatation. They are a true parietal prop, inserted into the arterial lumen through a percutaneous approach. The middle-term results of iliac and femoropopliteal implants are very encouraging, and they suggest that this technique may be a very useful complement to transluminal angioplasty in cases of poor results or recurrence. The insertion of an endoprosthesis also allows to extend the indications of transluminal angioplasty to cases that had been regarded as hardly favorable so far: long, irregular stenosis, iliac obliteration, etc. PMID- 1940647 TI - [Traumatic arterio-venous fistula. Experience with 9 cases]. AB - Traumatic arteriovenous fistulas (TAF) are rare forms of vascular injuries. The authors report an experience of nine new cases. Three of them result from a minor traumatism, while the six others are iatrogenic. The symptoms and the physical examination are very helpful in the diagnosis. Selective arteriography is the most useful paraclinical examination to confirm the affection and for the choice of the mode of therapy: surgery, selective arterial embolization, alone or used with surgery according to the characteristics and the location of the fistula. PMID- 1940648 TI - [In situ bypasses in limb salvage. Late results and patency factors]. AB - One hundred limbs with critical ischemia (stages III and IV) were saved from 1983 to 1987 by in situ venous bypass at the lower femoropopliteal or femorotibial level. The average age of the patients was 66 (40-89) years. The surgical indication involved 51 cases of stage III ischemia and 49 of stage IV. The etiology of the ischemia was occlusive chronic arteritis (n = 67), diabetic arteritis (n = 20), embolic disease (n = 10) and aneurysmal disease (n = 3). The systolic pressure index in the ankle recovered an average value of 0.42 preoperatively. In 48 cases, the distal implantation of the graft was on the lower popliteal artery, and on the arteries of the leg in 52 cases. During the immediate postoperative period, 8 patients died and 13 underwent amputation. At 5 years, the limb salvage rate was 72%. The primary patency at 5 years, calculated with the actuarial method, was 51% and the secondary patency at 5 years was 62%. Among the factors likely to significantly influence patency, only the site of the lower anastomosis and the quality of the III and IV segments of the popliteal artery were selected (p less than 0.05), while the number of patent vessels in the leg and the clinical stage did not influence patency. PMID- 1940649 TI - [Venous thrombosis in gastroenterology]. AB - Venous thrombosis involving the digestive tract affects the suprahepatic veins and the terminal part of the inferior vena cava, the portal vein and its roots. The etiology and diagnosis of this condition have made considerable progress. A thrombogenic disease can now be recognized in 90% of cases of involvement of the suprahepatic veins, and 75% of portal involvements. The most frequent causes are primary myeloproliferative syndromes, paroxysmal nocturnal hemoglobinuria, hereditary deficiency in coagulation proteins and circulating anticoagulants. The cause of involvement of the portal vein also include insults during biliary surgery and abdominal infections, particularly those caused by Bacteroides fragilis. Mechanical involvement due to compression finally plays a minor role in the etiology. Noninvasive techniques of diagnosis are now available, including ultrasound, computed tomography and magnetic resonance imaging. The expression of obstruction of the suprahepatic veins predominantly consists in ascites and hepatomegaly. Thrombosis of the portal vein preserving the mesenteric arches usually remains asymptomatic until the intrahepatic block is revealed by a digestive hemorrhage caused by portal hypertension. Isolate involvement of the splenic vein exceptionally causes the rupture of gastric or esophageal collateral veins. The treatment should combine the prevention of further thromboses by anticoagulants and the specific treatment of the venous obstruction. In case of suprahepatic obstruction, there are several methods of restoring a canal of drainage for hepatic blood. Their indications depend on the patency of the inferior vena cava and of the portal vein. In case of portal obstruction, portal systemic bypass is feasible only if one of the major roots of the portal vein still is patent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940650 TI - [Cerebral venous thrombosis. Report of 76 cases]. AB - Progress in neuroimaging has led to a considerable change in our knowledge of cerebral venous thrombosis (CVT). Together with a series of 76 cases, a review of literature is presented. CVT is a far from negligible variety of stroke. It may occur at any age and despite numerous causes (nowadays mostly non infective), the proportion of cases of unknown aetiology remains around 25%. Superior sagittal sinus and lateral sinus are the most frequently involved, often associated with cortical vein thrombosis. Cavernous sinus thrombosis remains the most common form of septic thrombosis. Thrombosis of the galenic system and of cerebellar veins are uncommon. The clinical picture is extremely variable with a mixture of focal signs (deficits or seizures) and symptoms of raised intracranial pressure. The mode of onset is also variable, over hours, days, weeks or months. The presentation can thus be very misleading, simulating an arterial stroke or an abscess, an encephalitis, a tumor or a pseudo-tumor cerebri. CT scan is crucial to rule out other conditions and angiography to confirm the diagnosis of cerebral venous thrombosis. MRI is very performing since it visualizes the thrombus itself and allows a non invasive follow up. Most cases have a benign course but mortality is still around 30% in infective cases and 10% in non infective ones. Although it has long been debated, the benefit of anticoagulant (heparin) is now well established. PMID- 1940651 TI - [Thrombosis of renal veins]. AB - According to whether they are acute or progressive, complete or partial, uni- or bilateral, renal venous thromboses have quite various clinical expressions and biological consequences. The diagnosis is readily suggested by acute pain in the side with an increase in the size of one or both kidneys, associated with hematuria, proteinuria, or in case of renal failure, which is characteristic of acute bilateral thrombosis. On the other hand, chronic thrombosis of a renal vein is sometimes suggested only when complications such as pulmonary embolism occur. This explain why it is often discovered on autopsy. The diagnosis is confirmed on the basis of radiology, with ultrasound combined with vascular Doppler becoming increasingly important. Renal venous thrombosis may have various causes: disorders in renal blood flow, especially in the acute forms in newborns; hypercoagulability, in particular in nephrotic syndromes and above all in extramembranous glomerulonephritis; extension of vena cava thrombosis; retroperitoneal diseases involving the renal pedicle or extension of a renal tumor. The treatment of renal vein thrombosis is mainly medical and based on anticoagulants. The role of fibrinolytic treatment is controversial. Surgery is exceptional. PMID- 1940652 TI - [Hemorheology in clinical practice. Introduction to the notion of hemorheologic profile]. AB - Although the non-Newtonian characteristics of blood have now been accurately defined, the influence and effect of a hyperviscosity syndrome at the onset of ischemia and in oxygen transport to the tissues remains within the realm of assumptions. Using a simple theoretical approach it can be shown that oxygen transport capacity to the tissues is proportional to the radio H/eta s (where H = hematocrit, eta s = blood viscosity), as long as vascular bed geometry remains constant (with no sign of compensatory vasodilation). With the help of examples, the authors show the changes in oxygen transport as a function of various rheological parameters (red cell aggregation ans deformability). Further, the authors introduce the concept of a hemorheological profile for taking all the hemorheological parameters into consideration and for standardising the presentation of the results for hyperviscosity syndromes. PMID- 1940653 TI - [Erythrocyte aggregation in vascular disease. Influence++ of hypertension]. AB - In vascular diseases, when the vasomotor reserve is exhausted, microcirculation is strongly dependent on blood fluidity. For patients with vascular disorders, it was therefore decided to evaluate red blood cells (RBC) aggregation and disaggregation (SEFAM erythro-aggregometer) which are important factors determining blood viscosity in low flow areas. Our results show that, in essential hypertension (EH), RBC aggregation is significantly increased (+15%), and disaggregation is decreased (-20%). The highest frequency of troubles was found in EH. This observation led to exclusion of EH subjects in all the other studied pathological groups. When EH is excluded from a group of 70 patients with cerebrovascular disorders (CVD), we did not observe significant changes in RBC aggregation. However, in essential and post-thrombotic venous insufficiency there remains a significant increase in RBC aggregation (+10%) and a decrease in disaggregation (-13%). In diabetes, disaggregation is more disabled than for controls (-16%). In all these pathologies presence of EH magnifies the abnormalities, or makes them appear like in CVD. This study underlines the critical importance of taking the influence of hypertension into consideration when evaluating RBC aggregation in vascular pathology. The increase in RBC aggregability and in the shear resistance of the aggregates, when present in vascular pathology, is likely to add a burden to the circulatory system already hindered by a deficient vasomotor regulation system. PMID- 1940654 TI - [Alterations in erythrocyte membrane. Effect of neutrophil activation]. AB - White blood cells, especially polymorphonuclear neutrophils (PMN), are known to alter some hemorheological parameters. Most of in vitro results have been obtained with passive PMN. Stimulated PMN also lead to other hemorheological changes. In our study, we have firstly activated PMN with opsonized zymosan and collected a PMN-free supernatant after 30 minutes activation. This supernatant was secondarily incubated with erythrocytes either in whole blood or in suspension. After 10 minutes incubation, hemorheological parameters were evaluated: 1) red blood deformability (RBC) (Ektacytometer* Technicon), 2) RBC filtration (Hemorheometer MK 1), 3) RBC aggregation (Erythroaggregometer* Sefam), 4) Plasmatic and whole blood viscosities (Low Shear 30* Contraves). Our results show that activated PMN-supernatant increases rigidity index (IR) of RBC in suspensions (IR of RBC control = 14.59 +/- 3.30 towards RI of incubated RBC = 22.91 +/- 7.06 p less than 0.001). Other rheological parameters remain unchanged. Activated PMN suspenatant influence on RBC is slight but could suggest of an alteration of RBC membrane. With an in vitro model of washed platelets aggregation, we have previously demonstrated that proaggregant activity of PMN supernatant was inhibited by specific Platelet-Activating Factor (PAF-acether) antagonists: BN 52021, BN 50723, Web 2086. We have so compared both effects of activated PMN-supernatant and synthetic PAF-acether on RBC membrane fluidity. Membrane fluidity was studied by fluorescence polarization of 4 probes embedded at different deep in the membrane of intact RBC. Similar modifications of RBC membrane fluidity are observed with either synthetic PAF-acether or PMN supernatant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940655 TI - [Hemorheologic effects following ergometric-controlled physical exercise]. AB - In collaboration with the Laboratory of Physiology, the Unity of Biorheology realized hemorheological studies on healthy volunteers who performed four kinds of well-controlled exercises on a cycle ergometer. Blood was always collected just before exercise and just after exercise. Rheological measurements were performed (blood and plasma viscosities, blood thixotropy and blood viscoelasticity) as well as biological (plasma proteins) and biophysical (osmolarity, pH) measurements. In all the cases, results show the importance of a hemoconcentration and its hemorheology consequences. PMID- 1940656 TI - [Erythrocyte aggregation in patients with monoclonal gammopathies: effect of plasma exchange treatment]. AB - Analyses of erythrocyte aggregation have been carried out in 15 patients with multiple myeloma or Waldenstrom's macroglobulinemia before and after plasma exchange. The volume of exchanged plasma was about 1.2-1.5 plasmatic mass. It was replaced by the same volume of a 4% solution of human albumin. Each treatment included at least 3 plasma exchanges at 48 hours intervals. The kinetic (aggregation times) and rheological (dissociation threshold) parameters of erythrocyte aggregation were determined before and immediately after each plasma exchange using a device based on the analysis of the backscattered light by a blood suspension. Before the first plasma exchange, erythrocyte aggregation measurements revealed a pronounced reduction in time aggregation and high values of dissociation thresholds indicating an hyperaggregation of red cells. The successive plasma exchanges produced very different changes in erythrocyte aggregation. For some patients, the aggregation parameters presented normal values from the first plasma exchange when similar changes were only noted after the second plasma exchange in other patients. Finally, in some cases, an hyperaggregation state was maintained after a series of three plasma exchanges. The influence of the nature and the concentration of monoclonal immunoglobulin as well as plasmatic fibrinogen are discussed. PMID- 1940657 TI - [Improvement of hemorheologic parameters in hemodialyzed patients treated with human recombinant erythropoietin]. AB - Recombinant human erythropoietin (rhu EPO) is the choice treatment of dialytic anemia; however, this therapy has side effects due to the increased number of blood components involved. It seemed to us worth assessing, by hemorheological study, the impact of such a treatment on blood flow properties, already impaired in this type of patients. This study was designed to measure the evolution of hemorheological parameters in 16 hemodialysed patients before and after 2.3 and 6 months of treatment with rhu EPO. Hemorheological work-ups included: erythrocyte filtration with a hemorheometer; blood and plasma viscosities (LS30), ATP and 2.3 DPG, RBC aggregation (Sefam erythroaggregameter), RBC morphology under a scanning electron microscope; blood counts and full biochemical work-ups were performed to explore renal function. The results showed, besides a significant increase in hemoglobin: normalized rigidity index, reflecting the better deformability of erythrocytes; a moderate increase in blood viscosity with uncorrected hematocrit, becoming significant after 6 months of treatment. This increase however did not reach the values that could be expected with the increased hematocrit (it was probably balanced by improved erythrocyte deformability, which is confirmed by the fact that with corrected hematocrit, blood viscosity decreases during treatment). Studying erythrocyte aggregation in hemodialysed patients reveals, in the absence of any treatment, a decrease in aggregation time and a higher dissociation threshold, which reflects a tendency to erythrocyte hyperaggregation enhanced by erythropoietin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940658 TI - [Aneurysms of the popliteal vein. Description of 2 cases]. AB - Primitive vein popliteal aneurysms are an extremely rare pathology whose treatment is still matter of controversy. Its rare incidence, the diagnostic and clinical problems ensuing to the possible pulmonary embolism, explain the interest developed by these lesions. The authors report two cases of popliteal vein aneurysm observed in their Institute and diagnosed because seat of vein thrombosis and source of pulmonary embolism. PMID- 1940659 TI - [Superior vena cava syndrome and Riedel's thyroiditis. Report of a case: review of the literature]. AB - The authors present the case of a 42-year-old female patient, initially admitted to hospital for the etiological diagnosis--which remained negative--and the treatment of a superior vena cava syndrome. This patient was seen again two years later as the superior vena cava syndrome recurred, while a thyroid syndrome appeared at the same time. Exeresis followed by a clinicopathological study demonstrated Riedel's chronic fibrous thyroiditis. The authors study the causal relationships between both conditions and their integration into multifocal fibroses. To their knowledge, this is the first case in which the superior vena caval syndrome is the site of occurrence of fibrosis, precedes the thyroid involvement. The new radiological technique at our disposal--CT, MRI--should allow more easily searching for the various sites of the fibrosing disease (biliary ducts, pancreas, duodenum, retroperitoneum, mediastinum, orbits), and immunological studies will make it possible to better classify them and define their pathogenesis. PMID- 1940660 TI - [Pelvic venous thrombosis and abnormality of the post-renal inferior vena cava]. AB - After angiography, a 17 year-old male patient presented a pseudo appendicular syndrome. After two poorly contributive surgical explorations, CT and MR Imaging showed atresia of the infra-renal vena cava, with pelvic thrombophlebitis extending to the gonadal and lumbar collateral circulation. PMID- 1940661 TI - [Stenosis of the right renal artery caused by the crura of the diaphragm. Report of a case]. AB - We present one case of arterial hypertension that had rapidly developed in a 23 year-old patient. Arteriography demonstrates a light stenosis of the root of the right renal artery and an obstruction of the superior mesenteric artery. After an attempt of intraluminal dilatation had failed, we decided to carry out double revascularization with a venous graft. Postoperative control arteriography demonstrated early thrombosis in both grafts. Our second operation directly approached the lesion on the root of the renal artery, which was stenosed by muscle fibers from the right column of the diaphragm muscle. The resection of these fibers released the renal artery, which was otherwise normal, as was confirmed by the postoperative arteriogram. In a second part, we discuss the etiology of this double stenosis and our surgical strategy. PMID- 1940663 TI - An eikonal-curvature equation for action potential propagation in myocardium. AB - We derive an "eikonal-curvature" equation to describe the propagation of action potential wavefronts in myocardium. This equation is used to study the effects of fiber orientation on propagation in the myocardial wall. There are significant computational advantages to the use of an eikonal-curvature equation over a full ionic model of action potential spread. With this model, it is shown that the experimentally observed misalignment of spreading action potential "ellipses" from fiber orientation in level myocardial surfaces is adequately explained by the rotation of fiber orientation through the myocardial wall. Additionally, it is shown that apparently high propagation velocities on the epicardial and endocardial surfaces are the result of propagation into the midwall region and acceleration along midwall fibers before reemergence at an outer surface at a time preceding what could be accomplished with propagation along the surface alone. PMID- 1940662 TI - Selection and mutation at a diallelic X-linked locus. AB - Equilibria and convergence of gene frequencies are studied in the case of a diallelic X-linked locus under the influence of selection and mutation. The model used is that of an infinite diploid population with nonoverlapping discrete generations and random mating. It is proved that if the mutation rates and fitnesses are constant and the mutation rates are less than one-third, then global convergence of gene frequencies to equilibria occurs. The phase portraits of the dynamical system describing the change of allelic frequencies from one generation to the next are determined. Convergence of gene frequencies is monotone from a certain generation on if every other generation is skipped. In the case without mutation, our proof of this monotone convergence simplifies G. Palm's original proof. PMID- 1940665 TI - Convergence of one-dimensional diffusion processes to a jump process related to population genetics. AB - A conjecture on the convergence of diffusion models in population genetics to a simple Markov chain model is proved. The notion of bi-generalized diffusion processes and their limit theorems are used systematically to prove the conjecture. Three limits; strong selection-weak mutation limit, moderate selection-weak mutation limit, weak selection-weak mutation limit are considered for typical diffusion models in population genetics. PMID- 1940664 TI - Multilocus autosomal sex determination. AB - The two basic one locus sex determination models, diploid individual sex determination and parental sex determination, are generalized to the multilocus framework. As in the single locus case, it is established that there are two classes of polymorphic equilibria, equilibria with even sex ratio and equilibria with equal allele frequencies in the two sexes. The condition for external stability of this second class equilibria to invasion by a "new" mutant allele is that a "new" appropriately averaged sex ratio near the equilibrium be moved closer to the even sex ratio. However, stable polymorphisms with noneven sex ratio are not those that have a sex ratio as close as possible to 1/2, in contrast to the single locus case. PMID- 1940666 TI - The searchlight hypothesis. PMID- 1940667 TI - Quantitative analysis of the Hopf bifurcation in the Goodwin n-dimensional metabolic control system. AB - We study, from a quantitative point of view, the Hopf bifurcation in an ODE model of feedback control type introduced by Goodwin (1963) to describe the dynamics of end-product inhibition of gene activity. We formally prove that the exchange of linear stability of the positive equilibrium in the n-dimensional Goodwin system with equal reaction constants coexists with a Hopf bifurcation of nontrivial periodic solutions emanating from this equilibrium, without any further restriction on the dimension n greater than or equal to 3 or on the Hill coefficient. The direction of the bifurcation and the stability and the period of the bifurcating orbits are estimated by means of the algorithm proposed by Hassard et al. (1981). PMID- 1940668 TI - Which locus has the oldest allele? AB - This paper studies aspects of the distribution of non-mutant ancestors of a sample of gametes in a two-locus infinitely-many-alleles model. The ancestral process of two gametes is considered in detail. Included are algorithms for calculating the probability that the oldest allele is from the first locus, and the expected age of the oldest allele. Extensions to an r-locus model in the cases of complete linkage and independence are also studied. PMID- 1940669 TI - On the uniqueness of endemic equilibria of an HIV/AIDS transmission model for a heterogeneous population. AB - In this paper, we examine an HIV/AIDS transmission model which has been widely used for studying the spread of HIV/AIDS through sexual contact. Some sufficient conditions are obtained for the uniqueness of endemic equilibrium. We also present a two-group model whose no-disease equilibrium is unstable but it has at least three positive endemic equilibria. PMID- 1940671 TI - Women impact dentistry. PMID- 1940670 TI - Ameloblastoma. A clinico-pathologic presentation. PMID- 1940672 TI - The treatment of TMJ disorders: a current update. PMID- 1940673 TI - Dr. William J. Gies's contribution to dental research, education, and journalism. PMID- 1940674 TI - Changes in open-field behavior of rats following spinal nerve root sectioning. AB - The open-field behavior of of 30 laboratory albino rats was measured after selective unilateral sectioning of either the L2, L3, L4 or L5 spinal nerve root using a novel abdominal entry. Although treated subjects displayed observable motor dysfunction of the operated limb, no differences were found in open-field ambulation, rearing, defecation or urination based either on the level of the sectioned nerve root or on the day the behavior was measured, suggesting that there was an effect of the treatment not measurable by standard statistical procedures, quite possibly due to the small sample size. PMID- 1940675 TI - Osteopathic vs. chiropractic education: a student perspective. AB - This study compares nationwide survey results from 506 second year students of 11 osteopathic schools and 881 students from the first and second academic year (third term/fourth quarter) of eight chiropractic colleges. Each student was given a questionnaire regarding his/her perspective on the education he/she was receiving. Both populations were questioned about whether or not they came from an osteopathic/chiropractic family, their application process, the efficacy of osteopathic manipulative therapy (OMT)/chiropractic adjustments, their first year attitude concerning the efficacy of OMT/chiropractic adjustments, the integration of osteopathic/chiropractic principles into the curriculum and the justification for separate health care professions. Osteopathic and chiropractic students entered their respective professions from nonosteopathic/non-chiropractic families. Although both populations selected their profession as a first and primary choice, chiropractic students were more substantially represented. Upon entering their program, osteopathic students were not convinced, but had an open mind concerning the effectiveness of osteopathic manipulative therapy (OMT), and were divided as to whether there is enough of a distinction between DOs and MDs to justify separate professions. Chiropractic students, on the other hand, entered their program convinced that chiropractic adjustments are effective, and saw a clear distinction between the roles of chiropractic physicians and medical doctors. PMID- 1940676 TI - Evaluation and manipulative therapy of patellar malalignment: a clinical review and preliminary report. AB - Patellar malalignment is difficult to diagnose, but can respond well to conservative care. This paper discusses the clinical and radiographic diagnostic features of patellar malalignment, as well as conservative care for this condition. PMID- 1940677 TI - The subluxation complex does exist. PMID- 1940678 TI - Commentary: belief in science and medicine. PMID- 1940679 TI - Bronchogenic carcinoma presenting as neuromusculoskeletal pain. PMID- 1940680 TI - Is there a chiropractic science? PMID- 1940681 TI - Chiropractic in Australia. PMID- 1940682 TI - Effects of cervical adjustments on lateral-flexion passive end-range asymmetry and on blood pressure, heart rate and plasma catecholamine levels. AB - The biomechanical and physiological effects of a single, unilateral lower cervical spinal adjustment delivered to the most restricted side of cervical lateral-flexion passive end-range were examined. Only healthy, asymptomatic male subjects who exhibited goniometrically verified lateral-flexion passive range of motion asymmetries of 10 degrees or greater on the morning of the experiment were chosen for the study. Posttreatment goniometric measurements revealed that in sham-adjusted controls, mean lateral-flexion asymmetries had not changed significantly during the 4-hr time period examined. However, in subjects who received lower cervical adjustments, dramatic ameliorations of asymmetry magnitude were observed which persisted throughout the entire 4-hr posttreatment time period. On the other hand, in the face of this rather robust biomechanical effect, heart rate and blood pressure measurements obtained at -60 and -15 min prior to treatments, and at 5, 30, 60, 120 and 240 min following treatments, revealed no significant differences between adjusted and sham-adjusted subjects at any of the time periods examined. Consistent with this, analysis of the plasma concentrations of norepinephrine, epinephrine and dopamine in serial blood samples collected at these same times also failed to reveal significant differences between treatment groups at any of the time periods examined. The results of this investigation indicate that lower cervical adjustments are capable, at least in asymptomatic subjects, of inducing relatively robust biomechanical effects related to passive cervical end-range capability without simultaneously inducing significant alterations in the overall activity of the sympathetic nervous system. PMID- 1940684 TI - An American clinic for traditional Chinese medicine: comparisons to family medicine and chiropractic. AB - Patient self-selection delimits the kinds of disorders treated by practitioners of acupuncture and other traditional Chinese modalities in the United States. Based upon a questionnaire administered to 200 first-time patients in a teaching clinic for traditional Chinese medicine (TCM) in California, it was determined that practitioners of TCM attract patients whose health problems would also be appropriate for management by family physicians, chiropractors or mental health professionals. Approximately one-third of presenting complaints can be categorized as presumed organic disorders (many of which may have been medical treatment failures); one-third comprise musculoskeletal problems and headaches; and one-third appear to be psychological or psychosomatic in nature. PMID- 1940683 TI - The comparative assessment of paraspinal tissue compliance in asymptomatic female and male subjects in both prone and standing positions. AB - Segmental bilateral paraspinal tissue compliance measures were obtained from 50 male and 50 female asymptomatic subjects (vertebral segments C7-L5). Interexaminer concordance for the taking of the measure was found to be extremely high (r greater than .90). Additionally, test-retest measures obtained from the same subjects initially, and again 15 min or 2 wk later indicated fairly low short-term as well as long-term temporal variabilities for the measure. The greatest levels of variability were encountered at lumbar segments, particularly with 2 wk intervals between assessments, and when measures were obtained with subjects in the standing, rather than prone, position. Data generated by this study suggest that tissue compliance assessments may provide useful information with respect to the contractile state of the paraspinal musculature at various regions or segmental levels. PMID- 1940685 TI - Systemic abnormalities in idiopathic scoliosis. AB - Sixty-five to ninety percent of all scoliosis is of unknown origin or idiopathic. During the last 30 yr, researchers worldwide have found a variety of abnormalities in tissues throughout the body including peripheral muscle, skin, ligaments, platelets, bone, intervertebral discs, serum and urine. The primary defects appear to be related to collagen and proteoglycan synthesis. The systemic abnormalities seen in idiopathic scoliosis cannot be explained by the biomechanical effects of the curvature. PMID- 1940686 TI - Development and use of clinical algorithms in chiropractic. PMID- 1940687 TI - The validation of the diagnosis "joint dysfunction" in the synovial joints of the cervical spine. PMID- 1940688 TI - A look in the mirror: a critical and exploratory study of public perceptions of the chiropractic profession in New Jersey. PMID- 1940689 TI - Assessment of cervicogenic vertigo. PMID- 1940690 TI - Commentary: stop paradigm erosion. PMID- 1940692 TI - Science in chiropractic clinical practice: identifying a need. PMID- 1940693 TI - Vae victis. PMID- 1940691 TI - Chiropractic in Australia. PMID- 1940694 TI - The incidence and significance of the posterior gastric artery in human anatomy. AB - This study examines the incidence of the posterior gastric artery in a series of 75 adult cadavers. We clearly identified the posterior gastric artery in 36 (48%) cadavers as a 1- to 2-mm vessel arising from the cranial border of the splenic artery within 3 cm of the celiac trunk and coursing dorsally to the posterior parietal peritoneum where it forms a fold before supplying the upper part of the posterior gastric wall. Identifying this vessel is difficult during surgery that compromises vascular tributaries of the stomach, and the obscure course and high incidence of this vessel necessitates awareness that, in a 75-85% gastrectomy, the short gastric artery or branches of the left gastric artery should be preserved since the posterior gastric artery will be sacrificed in 13% of these cases. PMID- 1940695 TI - Examination of collateral flow and anomalies of the left renal vein with clinical correlations. AB - The anatomy of the left renal vein, especially knowledge of collateral flow, is extremely important to the modern surgeon, since division of the left renal vein is common to many procedures. This study examines the left renal venous drainage system in 20 human cadavers for evidence of collateral flow and anomalies. Ten cadavers underwent dissection of the tissues surrounding the left renal vein, except for the left suprarenal and left gonadal veins, and 10 did not. Water and methylene blue were injected into the left renal vein to check for extravasation, and the veins were subsequently divided. There was no evidence of additional tributaries off the left renal vein as no extravasation occurred, and opening of the left gonadal and left suprarenal veins did not reveal any direct connections to the inferior vena cava. Thus, this experiment did not demonstrate evidence of a systemic collateral flow system draining the left kidney once the left renal vein was divided. Anomalies of the left renal venous drainage system occurred in six of 20 (30%) of cadavers, with one anomaly of the left renal vein itself (5%) manifested as a supernumerary left renal vein. The other anomalies included bifurcation of the gonadal vein, bifurcation of the suprarenal vein, the inferior phrenic vein draining into the left renal vein distal to the superior mesenteric artery, and the presence of a lumbar vein draining into the left renal vein in two cadavers. The lumbar veins may perhaps represent a normal variant. PMID- 1940696 TI - Cardiac angiosarcoma: a case report. AB - Primary neoplasms of the heart are rare and difficult to diagnose prior to surgery, even with modern imaging techniques. Often, the tumors are diagnosed only at autopsy. Angiosarcoma is the most common malignant neoplasm. This disease is most commonly found in middle-aged men, and the tumor is most often located in the right atrium. It commonly causes blood flow abnormalities, extensively infiltrates cardiac structures, and may extend through the heart wall to involve adjacent structures. Metastatic spread at the time of diagnosis is common, and surgical mortality is high. We present a case of primary angiosarcoma involving the right ventricle of the heart. This tumor developed 6 months after the patient had undergone coronary artery bypass surgery. The patient was initially thought to have a massive thrombus within the right ventricle but at surgery was found to have a malignant neoplasm invading the myocardium. Subsequently, he was found to have pulmonary metastases. A debulking procedure was performed, and the patient was started on chemotherapy. Rather prompt improvement occurred after the debulking procedure, but subsequent studies have indicated progression of the pulmonary metastases despite ongoing chemotherapy. PMID- 1940697 TI - The history of the small bowel. PMID- 1940698 TI - The personal and professional life of John Hunter. PMID- 1940699 TI - Cholesterol screening in children: a consensus statement--finally. PMID- 1940700 TI - Oral cancer. PMID- 1940701 TI - Motor neurone disease in Thailand: the clinical aspects of 77 patients. AB - This is the first large scale case series of motor neurone disease (MND) in Thailand. Seventy-seven patients were identified between 1978 and 1984 at Siriraj Hospital Medical School, Bangkok, Thailand. Fifty-five patients were male (71.43%) and the mean age of the patients was 51.55 (SD 14.26) years with the range of 17 to 78 years. Clinical classification of MND was categorized as progressive bulbar palsy (PBP), 26 patients (33.77%); amyotrophic lateral sclerosis (ALS), 42 patients (54.54%); and progressive spinal atrophy (PSA), 9 patients (11.69%). The mean age of PBP, ALS and PSA were in the order of 57.61 (SD 12.09), 52.81 (SD 11.18), and 28.11 (SD 9.44) years. Progressive spinal atrophy group was younger than PBP and ALS groups significantly at the P-value less than 0.05 by analysis of variance and Duncan tests. Fifty-three patients (72.60%) were resident in Bangkok and the central part of Thailand. The main presenting symptoms were wasting of the small muscles of both hands, leg weakness, and speech and/or swallowing difficulties. These symptoms were found in 62 patients (81.58%). Nearly half of the patients (48.68%) came to our care within six months of onset, 22.8 per cent presented with asymmetry of motor wasting, while limb and trunk fasciculation was seen in 73.61 per cent. Dysarthria, dysphagia and tongue fasciculation were recorded as 51.32, 48.68, 60.53 per cent respectively. Exaggerated deep tendon reflexes were noted as 65.79 and 80.26 per cent over the upper and lower limbs, while Babinski sign was elicited in only 23.3 per cent of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940702 TI - Risk factors in puerperal infection. AB - Puerperal infection is one of the most common obstetric complications which leads to certain serious sequelas for those parturients. The study of 92 postpartum women at Siriraj Hospital from April 1, 1980 to March 1, 1983 was conducted to investigate the risk factors of puerperal infection. All 92 cases were diagnosed for puerperal infection according to the criteria of the Joint Committee on Maternal Welfare. Irregular antenatal care or no antenatal care, sexual intercourse during the last week before delivery and pelvic examination during pregnancy were found to be important predisposing factors in the antepartum period. Pelvic examination during labor accounted for 78 per cent of the patients and played an important role, while operative obstetrics (30%) and concomitant diseases during pregnancy (27%) were the next significant factors. PMID- 1940703 TI - Application of problem-based learning in orthopaedic surgery for 5th year medical student at Prince of Songkla University. AB - Problem-based learning should be continued and extended to more topics. However, the steps and details of the process should be modified to each group of students. The students and tutors should have a period for preparing themselves for the process. The learning media should be improved in quality, quantity and variety to serve almost all of the students. PMID- 1940704 TI - Final diagnosis of "suspicious for malignancy" from bronchial washing cytology. AB - Our study showed that patients whose first bronchial washing cytology was reported "suspicious for malignancy" had 82 per cent positive predictive value for malignancy. Repeat bronchoscopy should be offered to those with a visible endobronchial mass, and transthoracic needle aspiration should be performed in patients with peripheral lesions. PMID- 1940705 TI - Rapid karyotyping in the second and third trimesters for fetuses at risk of chromosomal abnormalities at Chulalongkorn Hospital. AB - Transabdominal fetal blood sampling under ultrasonic guidance was performed in 20 fetuses at 18 to 34 weeks gestation. Pure fetal blood was obtained in all cases; 11 from the umbilical veins at the placental cord insertion, 7 from the fetal intrahepatic veins and 2 from the fetal hearts. Rapid karyotype was obtained within 7 days by fetal lymphocyte culture. Chromosomal abnormality was detected in 5 (25.0%) fetuses. Abnormal karyotype was found in 4 of 8 fetuses with structural malformations detected by antenatal ultrasound and in 1 of 5 fetuses of elderly mothers at advanced gestational ages. This suggested that in fetuses at risk of chromosomal abnormality, rapid karyotype should be obtained and fetal blood sampling is justified in the second or third trimester. PMID- 1940706 TI - Thyroid function test in patient with acute-severe-nonthyroidal illnesses. AB - Patients with acute-severe-nonthyroidal illnesses had FT4 and T3 values below the normal range with the magnitude of change greater for T3 than FT4. Some patients had depressed and some had elevated TSH values. In the recovery phase, FT4 levels appeared to rise before T3 levels and TSH exhibited an exaggerated increase. These results are consistent with other studies which suggest that dysfunction of the hypothalamic-pituitary-thyroid axis may be associated with anomalous results for thyroid function test parameters in patients with acute-severe-nonthyroidal illnesses. This anomaly should be given due consideration when interpreting results of thyroid function test parameters in such patients. PMID- 1940707 TI - Plasma amino acid patterns in normal Thais and in patients with chronic renal failure. AB - The effect of chronic renal failure (CRF) on the pattern of plasma free amino acid concentrations was studied in 22 healthy controls (group 1); 43 CRF patients of which serum creatinine levels were 2-4.9 mg/dl (group 2, n = 11), 5-10 mg/dl (group 3, n = 10), more than 10 mg/dl (group 4, n = 9), and chronically hemodialysed patients (group 5, n = 13). In all renal failure groups, plasma concentrations of eight free essential amino acids-isoleucine, leucine, lysine, methionine, threonine, tryptophan, tyrosine and valine and those of three non essential amino acids-alanine, glutamate and serine were significantly lower than those in controls. Plasma concentrations of free arginine, cystine, glutamate and serine were significantly higher in CRF patients. Patterns of change of plasma aminogram were similar among CRF patients regardless of the stages of renal function or dialytic treatment. Stepwise changes of some plasma free amino acids were observed as renal function became worse. The molar ratios of plasma free valine/glycine, serine/glycine and tyrosine/phenylalanine were decreased accordingly. Our study confirms the presence of abnormal plasma aminogram, specifically that of essential amino acids, in CRF. Therapeutic intervention is warranted but still needs further investigations. PMID- 1940708 TI - Elucidation on acidity and low glucose concentration in parapneumonic effusion. AB - Studies were conducted on three consecutive patients with parapneumonic effusions by (a) serial analyses of plasma -pleural fluid glucose, pH, PCO2, and antimicrobial levels, and (b) serial analyses to determine the pH and PCO2 levels of pleural fluids that underwent in vitro incubation, before and after antimicrobial administration. The pleural fluid pharmacokinetics of the three antimicrobials followed a large reservoir model by increasing drug levels gradually, reaching the peak values at about two to seven hours following administration, while serial pleural fluid glucose levels showed a delayed rise or no rise in concentration, respectively. The molecular weights of the three antimicrobials are greater than that of the glucose, thus suggesting that over utilization of glucose within the pleural cavity is more likely the cause of this situation than the transport defect. In the in vitro incubation study, the serial pleural fluid pH and PCO2 levels before antimicrobial administration progressively decreased, while those following the administration of antimicrobials were stable during the first few hours. The results indicate that, in cases of parapneumonic effusion, the inflamed pleurae and the infectious pleural fluid (empyema) over-utilizes pleural fluid glucose leading to increased fluid acidity. PMID- 1940709 TI - Bilateral facial nerve paresis in eosinophilic meningitis. AB - A 29-year-old man presented with headache, nuchal rigidity and bilateral facial paralysis. Lumbar puncture revealed eosinophilic CSF pleocytosis. Facial diplegia was improved by supportive treatment. Thus, eosinophilic meningitis is one of the etiologies of bilateral facial nerve paresis. PMID- 1940710 TI - Shrinkage of recurrent endometrioma, after danazol. AB - A 29-year-old woman presented with a history of primary infertility one year after excision of endometrioma of the left ovary. On the first pelvic examination at the Infertility Clinic, the uterus was of normal size, retroversion and rather fixed with 0.5 cm firm nodule at its posterior surface. There was a tense cystic mass about 4-5 cm at the right adnexa. Three months later this mass was noted to have increased in size and the ultrasound revealed a slight, thick wall cystic mass with the largest diameter of 7 cm. The impression was endometriotic cyst of the right ovary. The patient was put on danazol 200 mg daily. After 6 months of treatment, the right ovarian mass was found to be 3.3 cm in the largest diameter by ultrasound. So the medication was discontinued. The patient conceived on the third cycle after discontinuing danazol. A healthy male infant, birth weight 3,320 g was delivered by elective cesarean section at term. PMID- 1940712 TI - Transplacental passage of a human relaxin administered to rhesus monkeys. AB - A synthetic version of the human relaxin encoded by the human gene 2 (hR1x-2) was administered to pregnant rhesus monkeys (Macaca mulatta) on gestational days 141 158. Monkeys (three per group) received doses of 100 micrograms/kg or 2000 micrograms/kg as a continuous i.v. infusion over 2 h into a radial vein. One monkey in the low-dose group received, along with the unlabelled hR1x-2, 25.5 microCi/kg of the test material internally labelled with [35S]cysteine. Immunoreactive hR1x-2, as measured by enzyme-linked immunosorbent assay, appeared in all fetuses within 30 min (the first sampling time) of beginning the infusions. Peak fetal plasma levels of hR1x-2 were only 0.8-1.5% of the maternal values. Only 8-15% of the fetal serum radioactivity was hR1x-2. Radioactivity from maternal urine pooled over the 4-h experiment did not elute at the volume corresponding to hR1x-2, but near the column volume. PMID- 1940711 TI - Administration of growth hormone to pigs alters the relative amount of insulin like growth factor-I mRNA in liver and skeletal muscle. AB - The relative amount of insulin-like growth factor-I (IGF-I) mRNA was determined in the liver and skeletal muscle of market weight crossbred barrows (castrated male pigs) using a solution hybridization-nuclease protection assay. Pigs were given either 50 micrograms recombinant porcine GH per kg body weight or vehicle daily for 24 days i.m. They were fed corn-soybean meal diets containing either 140 or 200 g crude protein/kg (low or high protein). The percentage of muscle in the carcasses of pigs given GH was greater (P less than 0.01) than that of controls. Relative to controls, GH increased (P less than 0.05) the amount of liver IGF-I mRNA by 2.7-fold in pigs fed the low protein diet and 3.0-fold in pigs fed the high protein diet. The amount of IGF-I mRNA in the muscles of GH treated pigs was 77% and 84% of control pigs in those fed the low and high protein diets respectively (P less than 0.08). GH increased (P less than 0.001) the serum concentration of IGF-I 1.6-fold in pigs fed the low protein diet and 2.0-fold in those fed the high protein diet. These results indicate that the administration of GH to pigs influences the relative amount of liver IGF-I mRNA. The increased amount of liver IGF-I mRNA and the increased serum IGF-I concentrations suggest that IGF-I plays an endocrine role in mediating GH-induced muscle hypertrophy in pigs. PMID- 1940713 TI - Roles of progesterone and oestradiol in determining the temporal sequence and quantitative expression of sexual receptivity and the preovulatory LH surge in the ewe. AB - In a series of experiments using a quantitative method for measuring receptivity and implants that allowed rapid and controlled changes in the blood concentrations of oestradiol-17 beta and progesterone, we have re-examined the roles of these steroids in the induction of sexual behaviour and the LH surge in ovariectomized ewes. Progesterone priming was found to increase the proportion of ewes showing oestrus, reduce the latency to the onset of oestrus, and increase the 'intensity' of the behaviour as measured by the receptivity index, but it did not affect the size of the LH surge. Progesterone was able to facilitate the expression of oestrus even when it was withdrawn 8 days before oestrogen treatment, suggesting that it exerts its effect by restoring the sensitivity of the oestrogen-refractory animal to oestrogen. When it was present at the time oestrogen was administered, progesterone inhibited the stimulatory effect of oestrogen, but this effect disappeared as soon as the progesterone was withdrawn. Thereafter, expression of both the behavioural and endocrine responses was delayed by 24-30 h. These data show that the timing of the preovulatory behavioural and endocrine events is determined primarily by the time of progesterone withdrawal. The amount of oestradiol and the timing of any rise in concentration serve only to modulate these effects. PMID- 1940714 TI - The cell-adhesive effect of basic fibroblast growth factor on pituitary cells in vitro. AB - Both native and recombinant basic fibroblast growth factor (FGF) exerted a marked effect on the morphology of a pituitary clonal somatotroph-like cell line (MtT/S) in vitro. Addition of 10 pg-20 ng bovine basic FGF/ml caused the cells to flatten and spread out over the culture dish, the cells showing strong surface contact. Those in contact with the culture dish were epithelial in appearance, being polygonal, closely apposed and forming a pavement-like monolayer. Basic FGF inhibited cell proliferation in a dose-dependent manner at the higher concentrations tested (0.5-20 ng/ml). This cell-adhesive effect of basic FGF was also observed in normal dispersed pituitary cells. The observed stimulation of pituitary cell adhesion is the first report of a morphological effect of basic FGF on pituitary cells and could explain the physiological significance of basic FGF and its high concentration in the pituitary gland. PMID- 1940715 TI - Role of the placenta in the control of the ante-partum surge of prolactin in the rat. AB - A nocturnal surge of prolactin secretion occurs in the dark period preceding parturition in the rat. The aim of this study was to examine the role of the placenta in the control of this prolactin surge. Plasma prolactin and progesterone were measured by radioimmunoassay in serial blood samples collected after surgical removal of conceptuses during late pregnancy, and after intracerebroventricular (i.c.v.) injection of placental lactogen (PL) before the prolactin surge. In intact control animals, prolactin secretion remained low until a nocturnal surge of secretion occurred in the dark period preceding parturition, peaking at 269 +/- 51 (S.E.M.) micrograms/l at 03.00 h on day 21. Progesterone levels fell from greater than 200 nmol/l on day 19 to less than 40 nmol/l by 12.00 h on day 20 of pregnancy. PL levels during late pregnancy were modified by partial or complete removal of conceptuses at 10.00 h on day 19 of pregnancy. Removal of all but one or two conceptuses did not change the normal pattern of prolactin or progesterone secretion. Removal of all conceptuses, however, induced a large nocturnal surge of prolactin secretion, peaking at 211.7 +/- 78 micrograms/l at 03.00 h on day 20, 24 h earlier than the surge in intact animals. Progesterone levels after removal of all conceptuses fell to less than 40 nmol/l by 23.00 h on day 19, approximately 12 h before the decline in intact animals. Maintenance of increased progesterone levels after conceptus removal using silicone tubing implants significantly (P less than 0.05) reduced the peak of the premature prolactin surge to 79.7 +/- 18 micrograms/l at 05.00 h on day 20.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940716 TI - Growth hormone receptors in the liver and osmoregulatory organs of rainbow trout: characterization and dynamics during adaptation to seawater. AB - Specific binding sites for chum salmon growth hormone (sGH) were identified in the membranes obtained from tissues of rainbow trout. Specific binding of 125I labelled sGH (% per mg protein) was found in the liver (37%), ovary (6%), brain (6%), gill (4%), intestine (4%) and posterior body kidney (4%). Specific binding was not significant in head kidney, anterior body kidney, spleen, heart, skeletal muscle or skin. Scatchard analyses demonstrated the presence of a single class of high-affinity low-capacity receptors in the liver, gill, intestine and kidney. The association constants for the membranes from liver, gill, intestine and kidney were of the same order (1 litre/nmol). Chum salmon prolactin did not inhibit the binding of 125I-labelled sGH to receptors in the liver, gill, intestine and kidney. Transfer of rainbow trout from fresh water to 80% seawater evoked a rise in plasma concentration of GH and a significant decrease in the GH binding to the liver membranes after 1 day. Binding in the gill and kidney was not altered significantly. Membranes were treated with 4 mol MgCl2/l to remove bound GH from the receptors, and the results indicated that the reduction in binding in the liver after transfer to seawater was probably due to receptor occupancy by increased endogenous GH. The occupancy of liver GH-binding sites was maximal 4 days after transfer. Total (MgCl2-treated) binding sites in the liver increased significantly 14 days after transfer. Scatchard analysis indicated that receptors were altered in capacity without changes in binding affinity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940717 TI - Long-term effects of recombinant human growth hormone treatment on skeletal maturation and growth in female rhesus monkeys with normal pituitary function. AB - Female rhesus monkeys (n = 5), having normal pituitary function, were treated for 50 months with recombinant human growth hormone (rhGH; 250 micrograms/kg) 3 days/week (Monday, Wednesday and Friday) and rates of growth were compared with a group of age-matched untreated females (n = 6). Treatment was initiated at 20 months of age, approximately 10 months before the expected age of menarche. Long term treatment with rhGH accelerated bone maturation and increased the velocity of increase in crown-rump length, tibia length and body weight. The period of acceleration occurred coincident with the occurrence of spontaneous puberty. Body measurements remained larger in the treated females until growth ceased. Long term rhGH treatment increased final adult crown-rump length by some 3%, with a slight increase in tibia length and body weight, without having any untoward effects on reproductive capacity or health. One treated animal exhibited higher estimates of antibodies to rhGH throughout the study period, and this female also had a smaller increment in crown-rump length than the other treated females. These data suggest that long-term treatment of normal-pituitary females with rhGH augments crown-rump growth without any untoward effects of health. PMID- 1940718 TI - Evidence against a role for blastocyst-secreted oxytocin in early pregnancy maintenance in sheep. AB - Analysis of ovine conceptus RNA by slot blotting, Northern analysis and nested polymerase chain reaction failed to detect oxytocin-neurophysin prohormone mRNA. Probes used hybridized with both the 3' end of the prohormone mRNA and the oxytocin-coding sequence. Northern analysis of bovine and porcine conceptus RNA was also negative, and polymerase chain reaction demonstrated oxytocin neurophysin mRNA in ovine corpus luteum, but not in human corpus luteum or decidua, or in ovine endometrium. Infusion of oxytocin into the uterine lumen in cyclic ewes between days 9 and 19 or 20 after oestrus failed to prolong the luteal phase of the cycle and had no effect on endometrial oxytocin receptor concentrations or uterine prostaglandin F secretion. Oxytocin administered systematically prevented luteolysis and reduced uterine prostaglandin F secretion. Taken together, these data suggest that blastocyst-derived oxytocin is unlikely to contribute to corpus luteum maintenance in early pregnancy. They are inconsistent with a previous report that the ovine blastocyst synthesizes and secretes oxytocin. PMID- 1940719 TI - Diurnal changes in the plasma concentrations of LH and hypothalamic contents of LHRH-I and LHRH-II in the domestic hen. AB - Diurnal changes of LH secretion in sexually immature hens of 9, 11, 13 and 15 weeks of age consisted of 25-40% increases in the mean concentrations of LH in plasma between 15.00 and 18.00 h, i.e. between 2 h before and 1 h after the onset of darkness. During this time there was a tendency for the mean contents of LHRH I in the anterior hypothalamus and posterior hypothalamus to increase by 21-74% and 20-56% respectively. In hens of 9 and 15 weeks, diurnal changes in the plasma concentration of LH closely paralleled those of LHRH-I content in the posterior hypothalamus. In contrast, the diurnal rhythm of LH secretion in hens of 11 and 13 weeks was more marked and plasma concentrations of LH continued to rise steeply between 18.00 and 21.00 h, i.e. between 1 and 4 h after the onset of darkness. At 11 weeks, this was associated with a reduction (P less than 0.01) in the contents of LHRH-I and LHRH-II, particularly in the anterior hypothalamus. In laying hens, a diurnal decline (P less than 0.01) in the plasma concentration of LH between 1 and 4 h after the onset of darkness was preceded by a fall (P less than 0.05) in the content of LHRH-I in the posterior hypothalamus and in the total hypothalamic content of LHRH-II (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940720 TI - The use of low doses of ACTH in the investigation of adrenal function in man. AB - We have investigated the adrenal response, in eight healthy adult men, to low doses of ACTH(1-24) in order to define a dose which will elicit a response similar to that obtained with the short Synacthen test. The studies were performed at 14.00 h and blood samples were withdrawn at 5-min intervals after an i.v. bolus injection of ACTH(1-24). The sampling interval was crucial in determining the timing of the peak response. Using sampling times of 0, 10, 15, 20, 25 and 30 min ensured detection of 47 out of 48 peaks. A dose-dependent rise in plasma cortisol concentration was observed with bolus injections of ACTH(1-24) between 30 and 250 ng/1.73 m2 body surface area. Increasing the dose to 500 ng/1.73m2 (500 times less than that used in the short Synacthen test) elicited an increment of plasma cortisol concentration of 200 nmol/l or greater in all subjects. Pretreatment with dexamethasone (1 mg) did not alter the timing of the peak cortisol concentration but blunted the increase (pretreatment: median, 159 nmol/l; range 83-239; on dexamethasone; median 62 nmol/l; range 21-207; P = 0.04). These data suggest that a dose of ACTH(1-24) of 500 ng/1.73 m2 satisfies the criteria of the short Synacthen test and may provide a useful method of investigating adrenal function. PMID- 1940721 TI - Leakage after lateral condensation with finger spreaders and D-11-T spreaders. AB - The purpose of the study was to determine the leakage after lateral condensation with the use of finger spreaders and D-11-T spreaders. Fifty root canals were instrumented, and laterally condensed with gutta-percha and Grossman's cement. In 20 canals finger spreaders were used for the condensation and in a further 20 canals D-11-T spreaders were used. After 24 h in 100% humidity, the roots were painted with nail polish except for their apical 2 mm, which remained exposed. Five canals were not obturated (negative control) and five canals were obturated and the apices sealed with sticky wax (positive control). The expressed root tips were suspended in 2% methylene blue dye for 48 h. The teeth were then split longitudinally and the apical leakage measured and compared for each group. The results obtained by the positive and negative control teeth confirmed the effectiveness of the methodology used. Average dye penetration for the finger spreaders was statistically significantly less than for the D-11-T spreaders. Dye penetration of more than 0.5 mm occurred in 6 roots for the finger spreaders and in 12 roots for the D-11-T spreaders. PMID- 1940722 TI - Detection of immunoglobulins from explant cultures of periapical lesions. AB - The presence of immunoreactive cells in periapical inflammatory lesions suggests that immune responses participate in the disease process. The purpose of this study was to determine the presence and concentration of immunoglobulins in the supernatant fluids of explant cultures of periapical lesions. Ninety periapical lesions that had been contiguous with the apex of a root were removed and maintained in explant cultures for 96 h. Tissue culture medium was replenished at 24, 48, 72, and 96 h. Double diffusion in agarose assays demonstrated the presence of IgG in 100% of the 24-h supernatant fluids and IgA in 65% of the 24-h supernatant fluids. However, IgM was not detected. Radial immunodiffusion assays were used to detect and quantitate IgG, IgA, and IgM in samples of 24-h supernatant fluids from 90 explant cultures. IgG was the predominant immunoglobulin followed by IgA. A radioimmunosorbent test was used to detect and quantitate IgE in samples of 24-h supernatant fluids from 90 explant cultures. Forty of the 90 supernatant fluids contained measurable IgE. All detected immunoglobulins decreased in concentration in daily supernatant fluids with time (24, 48, 72, and 96 h) in the culture. PMID- 1940724 TI - Dentinal permeability of the dog canine after exposure of a cervical cavity to the beam of a CO2 laser. AB - The dentinal permeability of the axial wall of a class V cavities in the canine of the dog was analyzed before and after its laser CO2 irradiation at two energy levels: 285 J per cm2 and 570 J per cm2. The sealing of the exposed dentin was verified by means of a pellet of cotton wool placed in contact with the axial wall and on which 20 microliters of a 50 mg per ml solution of noradrenaline was injected with a micrometric syringe. The transdentinal passage of noradrenaline induces a vasoconstriction of the pulp which is attested by a drop in its blood pressure. The absence of any variation in the pulpal pressure is an indication of the sealing to noradrenaline of the dentinal wall irradiated with an energy level of 570 J per cm2. This experimentation illustrates that it is possible to obtain dentinal sealing by means of laser irradiation without affecting the underlying pulp. The quality of this reduction in permeability is dependent upon the different factors which define the energy level. PMID- 1940723 TI - The efficacy of step-down procedures during endosonic instrumentation. AB - The step-back method of root canal preparation may not be suitable for endosonic files as they may be prevented from working efficiently within the apical region. This study determined the debris present in the apical portion of the canal after using three different endosonic instruments and compared the step-back versus the step-down technique; the latter involves initial preparation of the upper regions of the root canal which may reduce file constraint. Thirty-six teeth were prepared by either the step-back or step-down method using endosonic generators (magnetostrictive, piexoelectric, and sonic). Preparation times were standardized so that files were used for the same period. From scanning electron micrographs, debris removal was scored on a four-point scale by four clinicians. A log linear analysis showed that there was significantly less debris present with the step down method using piezoelectric and sonic devices. More debris was present when files driven by a magnetostrictive instrument were used with the step-back method. This study showed that the step-down method may be useful when using certain types of endosonic generators. PMID- 1940725 TI - Endodontic retreatment in large and small straight canals. AB - The change in original canal size and location after canal preparation and after reinstrumentation using a step-back technique was studied in small and large canals with less than 20-degree curvature. Teeth were mounted in jigs and then sectioned. The jig permitted the sectioned teeth to be repositioned exactly. Slides were made of the canal in the coronal, middle, and apical at the following intervals: before instrumentation, after instrumentation, and after reinstrumentation. The increase in canal area and the direction of movement was measured. The data were analyzed by ANOVA and Duncan's multiple range test. The results showed: (a) All canal areas increased after retreatment. The retreated apical canal increased in area significantly more (25.4%) than middle (4.0%) or coronal (3.0%) regardless of whether the canal was large or small. (b) The retreated canals tended to move in the same direction they moved after first instrumentation. PMID- 1940727 TI - Four root canals in a mandibular second premolar. AB - A case report is presented involving the successful endodontic treatment of a mandibular second premolar with four canals in a single root. Statistics of morphological variations are irrelevant when the involved tooth is an anomaly. PMID- 1940726 TI - A pilot study of Japanese green tea as a medicament: antibacterial and bactericidal effects. AB - Antibacterial and bactericidal actions of extracts of four kinds of Japanese green tea were tested against 24 bacterial strains isolated from infected root canals. The extracts of all four teas had antibacterial and bactericidal actions against many of the bacteria. PMID- 1940728 TI - Autotransplantation using endosseous implants as stabilizers. AB - The surgical transfer of a tooth from one site to another in the same individual is known as autotransplantation. Usually the tooth transferred is an unerupted or partially erupted third molar which is placed into a first molar position with some external fixation. In this case report, the first molar was already missing and the second molar was hopeless. An erupted third molar was autotransplanted into the second molar site and endosseous implants were used to stabilize the tooth. A fixed bridge was placed 6 months later and the progress followed for 4 yr. PMID- 1940729 TI - Generic tricalcium phosphate plugs: an adjunct in endodontics. AB - Unusual endodontic situations may necessitate an immediate plug inside the tooth in order to dry the canal system and provide resistance to condensation. Generic tricalcium phosphate is a powder that when hydrated handles like silver amalgam and is condensable into a hard plug deep inside the tooth. It is fast, relatively technique insensitive, comfortable postoperatively, biocompatible, inexpensive, and readily available. A practical technique is presented and two case reports illustrate its use as an apical plug and a furcation perforation plug. PMID- 1940730 TI - The concentration of prostaglandin E2 in human periradicular lesions. AB - Prostaglandins (PG) have been implicated in the genesis of periapical lesions. Periapical specimens from patients with clinical signs and symptoms of chronic and acute apical periodontitis were obtained and immediately frozen in liquid nitrogen. Periradicular tissues from unerupted third molars were frozen and used as controls. The concentration of PGE2 was determined by radioimmunoassay. Low levels of PGE2 were found in the control tissues as compared with those detected in chronic and acute lesions. Significantly higher levels of PGE2 were found in acute lesions than those found in chronic lesions. The results show that acute lesions have higher concentrations of PGE2 than chronic lesions and confirm the role of prostaglandins in the pathogenesis of human periapical lesions. PMID- 1940731 TI - Biosynthesis of IgG in periapical lesion explant cultures. AB - The presence of immunoglobulins has been demonstrated in periapical inflammatory lesions associated with endodontic disease. The purpose of this study was to determine if IgG is synthesized in vitro in explant cultures of untreated periapical inflammatory lesions and to determine the level of IgG in isolated samples. Periapical lesions associated with infected root canals were removed from the roots and cultured in tissue culture medium containing tritiated amino acids. Supernatant fluids from the explant tissue cultures were passed through staphylococcal protein A affinity columns to isolate IgG. When the staphylococcal protein A eluents (24-h samples) from six periapical lesions were used in double diffusion in agarose assays, the presence of IgG was demonstrated in all the samples. Radial immunodiffusion assays to quantitate the IgG in staphylococcal protein A eluents showed that the levels of IgG detected in each successive daily supernatant fluid always decreased or else fell below the lower limits of detection. The in vitro biosynthesis of IgG in explant cultures of periapical lesions was demonstrated by the incorporation of tritiated amino acids into isolated IgG. PMID- 1940732 TI - Effect of coronal-radicular flaring on apical transportation. AB - The purpose of this study was to evaluate the effect early and late radicular flaring has on apical canal transportation when using balanced force instrumentation. Sixty-six extracted human teeth with curvatures ranging from 20 to 65 degrees were equally divided into two groups. Canals were cleaned and shaped using balanced force and one of two flaring techniques. A pre- and postoperative double exposure radiographic technique was used to evaluate apical canal transplantation. While early radicular flaring made instrumentation much easier, no significant differences were found when comparing apical transportation between the two experimental groups. PMID- 1940733 TI - An ultrastructural and immunohistochemical study of human dental pulp: identification of Weibel-Palade bodies and von Willebrand factor in pulp endothelial cells. AB - Special and specific immunohistochemical techniques as well as routine transmission electron microscopy were used to identify the presence of von Willebrand factor (vWF), a blood clotting factor essential to normal hemostasis, and Weibel-Palade bodies (WPB's), respectively, in the endothelial cells lining the blood vessels from both normal and inflamed human pulpal tissues. In human endothelial cells, WPB's are peculiar and specialized organelles which store vWF. All classes of blood vessels (capillaries, arterioles, arteries, venules, and veins) were vWF positive. The fine structural studies showed similar results with regard to the presence of WPB's. Interestingly, morphometric analyses conducted on the same tissues using either light or transmission electron microscopy showed that significantly more vWF-positive blood vessels were seen in the inflamed tissues. In agreement with the latter observation, transmission electron microscopy showed that more vascular endothelial cells contained WPB's in the inflamed tissues when compared with the normal tissues. From this it appears that during pulpal inflammation, the cascade of events associated with hemostasis may be activated with the increased synthesis and release of vWF by endothelial cells. PMID- 1940734 TI - Effect of water leaching the adhesion of composite resin to bleached and unbleached bovine enamel. AB - Standardized cylinders of light-cured composite resin were bonded to the ground labial enamel surface of bovine incisor teeth that had been immersed in double distilled water for 7 days after having been (a) immersed in hydrogen peroxide for 5, 30, or 60 min, then etched for 60 s with 37% phosphoric acid; (b) immersed in saline for 5, 30, or 60 min, then etched for 60 s with 37% phosphoric acid; (c) etched with 37% phosphoric acid for 60 s, then immersed in hydrogen peroxide for 5, 30, or 60 min; or (d) etched with 37% phosphoric acid for 60 s, then immersed in saline for 5, 30, or 60 min. The enamel surface was washed with water for 1 min and dried with compressed air for 30 s prior to applying the resin. The tooth and applied resin were stored in water at 37 degrees C for 1 day prior to shear and tensile testing. A total of 192 specimens was used, 8 for each enamel preparation mode, for each time period, and for each test. Test values were tabulated and statistically analyzed. Analysis of variance revealed significantly higher bond strength values (p less than 0.005) for hydrogen peroxide-treated as compared with saline-treated specimens. A significant interaction was also noted between test solution and etching order. Scanning electron microscopic examination of failed shear- and tensile-tested specimens revealed no significant solution-related differences in the fracture pattern or the resin quality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940735 TI - The solvent effects of calcium hydroxide irrigating solution on bovine pulp tissue. AB - The solvent effects of calcium hydroxide irrigating solution (used alone and in combination with sodium hypochlorite) on bovine pulp tissue were studied. Forty pieces of pulp tissue weighing 90 mg each were treated with calcium hydroxide solution alone, calcium hydroxide and sodium hypochlorite alternated, sodium hypochlorite alone, and saline alone. Each piece of tissue was treated for 32 min. Desiccated pretreatment and posttreatment weights were compared. There was no significant difference between the dissolution capability of calcium hydroxide solution used alone and of saline. No significant difference was noted between calcium hydroxide solution and sodium hypochlorite used alternately, and sodium hypochlorite used alone. However, both of these groups were significantly more effective at dissolving tissue than calcium hydroxide solution alone or saline. Calcium hydroxide solution was an ineffective solvent of pulpal tissue. If tissue dissolution is desired during root canal therapy, the use of calcium hydroxide solution as the sole irrigant is no more effective than saline. PMID- 1940736 TI - Detection and treatment of multiple canals in mandibular premolars. AB - The endodontic treatment of mandibular premolars may not be successful because of failure to recognize and/or treat multiple canals when they are present in these teeth. Factors such as an awareness of data pertaining to the number of canals, knowledge of canal morphology, correct radiographic interpretation, and tactile examination of canal walls are important in detecting the presence of multiple canals. These factors, as well as guidelines for subsequent canal preparation and obturation, are provided. PMID- 1940737 TI - Treatment considerations in a geminated maxillary lateral incisor. AB - A patient with anomalous maxillary lateral incisor was referred for endodontic therapy. A diagnosis of irreversible pulpitis of a geminated maxillary lateral incisor was made. The preoperative radiograph revealed an image of a single root canal but in fact the tooth had two separate and distinct root canals. Treatment considerations of this anomaly are discussed. PMID- 1940738 TI - Zebra Hunt. Peripheral ossifying fibroma. PMID- 1940739 TI - Reactivity of IgG from explant cultures of periapical lesions with implicated microorganisms. AB - The presence of IgG in periapical inflammatory lesions suggests that immune responses participate in the disease process. The purpose of this investigation was to study the reactivity of IgG from the supernatant fluids of explant cultures of periapical lesions with microorganisms implicated in infections of endodontic origin. Ninety periapical lesions that had been contiguous with the apex of a root were removed and maintained in explant cultures. A dot-enzyme linked immunosorbent assay (dot-ELISA) was used to demonstrate the presence of IgG in the supernatant fluids of the explant cultures reactive with a panel of microorganisms associated with infections of endodontic origin. The percentages of reactivity by dot-ELISA follow: Bacteroides intermedius (84%), B. buccae (12%), Porphyromonas (Bacteroides) gingivalis (50%), P. endodontalis (58%), P. asaccharolyticus (17%), Peptostreptococcus micros (44%), P. anaerobius (26%), Eubacterium alactolyticum (34%), Fusobacterium nucleatum (14%), and Actinomyces israelii (6%). At least one of the three species of B. intermedius, P. gingivalis, or P. endodontalis tested gave a positive dot-ELISA with 89% of the supernatant fluids from explant cultures of periapical lesions. A lack of cross reactivity of IgG in supernatant fluids from explants of periapical lesions was demonstrated for the four strains of black-pigmented Bacteroides/Porphyromonas by dot-ELISA. PMID- 1940740 TI - Specificity of antibodies present in human periapical lesions. AB - Various classes of immunoglobulins have been found in human periapical lesions. The specificity of secreted antibodies against antigens egressing from the root canal system has yet to be thoroughly investigated. The purpose of this study was to test the specificity of antibodies present in human periapical lesions. Human periapical biopsies were removed and cultured as organ culture explants. Antibodies present in the lesions were extracted in the cell culture fluids. A modified enzyme-linked immunosorbent assay was used to determine the presence, type, and concentration of different classes of antibodies against a number of commonly found bacterial species present in the root canal system. The data show the presence of specific antibodies (IgG, IgM, and IgA) against all 16 microorganisms tested. Peptostreptococcus micros, Actinomyces israelii, Staphylococcus intermedius, and Fusobacterium nucleatum produced significantly high levels of IgG antibodies in these lesions. PMID- 1940741 TI - Dynamic fracture of hybrid endodontic hand instruments compared with traditional files. AB - The purpose of this study was to analyze in vitro the dynamic fracture of some endodontic hand instruments. The K file and H file were tested as reference traditional files; the K-Flex, Flexofile, Unifile, and Helifile were tested as newly developed hybrid instruments. The files were mounted in a lathe and rotated with cyclical axial motion in the lumen of a curved tempered steel groove until failure occurred. The results showed that the life span of instruments, the distance between the instrument tip and the rupture point, and the resistance to fracture were dependent on the size and design of the instruments. Moreover, scanning electron microscopic photographs revealed two types of breakage patterns. The K file, H file, Unifile, and Helifile showed a distinct fracture starting point with crack striations and ductile fractures. The K-Flex and Flexofile showed only plastic deformations and axial fissures. PMID- 1940742 TI - Effectiveness of halothane used with ultrasonic or hand instrumentation to remove gutta-percha from the root canal. AB - This study compared halothane and chloroform used with hand or ultrasonic instrumentation to remove gutta-percha and sealer from root canals. Apically extruded debris, residual debris, time for filling removal, and amount of solvent used were determined. The differences in extruded apical debris and radiographically visible residual debris were not significant (p greater than 0.05). Ultrasonic instrumentation required significantly less time to remove the root canal filling than did hand instrumentation (p = 0.02). The only significant difference in the amount of solvent used occurred when the ultrasonic-chloroform group was compared with the hand instrumentation-chloroform group (p = 0.05). Halothane was found to be an acceptable alternative to chloroform for removing gutta-percha and sealer from the obturated root canal. PMID- 1940743 TI - Silver glass ionomer cement as a retrograde filling material: a study in vitro. AB - Comparison was made of the apical microleakage of retrograde fillings with amalgam and with silver glass ionomer cements using a modified dye penetration method. Forty instrumented human teeth were divided into four groups. Each group was characterized by a different retrograde filling material or technique: Group 1--silver glass ionomer (SGI); group 2--SGI with previous acid wash of the cavity; group 3--SGI in a previously acid washed cavity, protected with varnish; and group 4--zinc-free amalgam. A paper cone for dye adsorption analysis was placed in contact with retrofill and the main canal was obturated with thermoplasticized gutta-percha. All teeth were coated, immersed in methylene blue dye, and evacuated to assure complete penetration of the dye in any possible void. Later the teeth were cleared and evaluated under stereomicroscope. Statistical analysis showed that group 1 had the least microleakage of all. In addition, the biocompatibility of the SGI and varnish was compared with that of amalgam using the 51Cr release evaluation method. The results showed that SGI and varnish were less cytotoxic than amalgam. It was concluded that SGI cement can be considered an alternative retrograde filling material. PMID- 1940744 TI - Effect of cementum defects on radicular penetration of 30% H2O2 during intracoronal bleaching. AB - Bleaching pulpless teeth with 30% hydrogen peroxide has been reported to cause external cervical root resorption. It has been hypothesized that H2O2 penetrating through open dentin tubules can initiate an inflammatory reaction which could result in root resorption. Extracted human premolars were treated endodontically and bleached intracoronally using the thermocatalytic technique. The teeth were divided into three groups; one group with no cementum defects at the cementoenamel junction, one group with artificial cementum defects at the cementoenamel junction, and another group with artificial cementum defects at the middle third of the root. The radicular penetration of 30% hydrogen peroxide in the three groups was assessed directly and compared using an in vitro model. Radicular penetration of hydrogen peroxide was found in all of the groups tested. The penetration of hydrogen peroxide was significantly higher in teeth with cementum defects at the cementoenamel junction than in those without defects. PMID- 1940745 TI - Histological study of furcation perforations treated with tricalcium phosphate, hydroxylapatite, amalgam, and Life. AB - One-hundred twenty experimental furcation perforations were created in the mandibular and maxillary premolars and molars of six rhesus monkeys. Tricalcium phosphate, hydroxylapatite, amalgam, and Life were used to repair the furcation perforations. The animals were sacrificed at the intervals of 2, 4, and 6 months after the experiment. Histological evaluation revealed lack of complete healing of furcation perforations repaired with any materials. Epithelium was present in the furcation perforations in both experimental and positive control groups. No hard tissue formation was observed in this study. Inflammation in the furcation area may be due to inadequate sealing ability of the repair materials. PMID- 1940746 TI - Relation of pre- and intraoperative factors to prognosis of posterior apical surgery. AB - The relation of preoperative and intraoperative factors to the prognosis of apical surgery was studied in 136 premolar and molar roots. The evaluated factors were: clinical signs and symptoms, size of the periapical lesion, root canal obturation, tooth restoration, apical retrofilling, and the operating surgeon. A significantly higher success rate was found in roots obturated 2 mm or shorter of the apex, in roots without post restoration, and after retrofilling of roots with apparently well-condensed obturation. The prognosis differed significantly following treatment by various operators but was unrelated to their experience. PMID- 1940747 TI - Vital bleach of hemorrhagic discoloration. AB - An unusual case is presented of a maxillary central incisor with hemorrhagic discoloration that was successfully treated with the thermocatalytic vital bleach technique. This case emphasizes the need for a thorough radiographic and clinical examination to include vitality tests when a patient presents with a discolored tooth. PMID- 1940748 TI - Complex facial radicular groove in a maxillary lateral incisor. AB - A case report of a developmental anomaly known as a radicular groove is presented. This case is unusual in that it is believed to be the first reported case of complex involvement of the entire facial aspect of a tooth root. An alveolar crest to apex facial root defect in a maxillary right lateral incisor of a 12-yr-old black female led to early pulpal necrosis and periapical rarefaction. Clinical and histologic findings as well as morphologic and treatment ramifications are discussed. PMID- 1940749 TI - Resistance to fracture of endodontically treated premolars restored with glass ionomer cement or acid etch composite resin. AB - MOD cavity preparations in 64 endodontically treated premolars were restored using four different methods. Copper rings were filled with commercial hard setting cement and the teeth were placed into the cement up to the level of the cementoenamel junction. The teeth were grouped according to restorative method, mounted in an Instrom T.T. machine, and the buccal walls subjected to a slowly increasing compressive force until fracture occurred. The force of fracture of the walls of each tooth was recorded and the results in the various groups compared. All teeth fractured in a similar manner irrespective of the restorative method used. The resistance to fracture of the teeth was the same when they were restored with glass ionomer cement as a base over which an amalgam or composite resin was placed or with acid-etched resin. When the entire cavities were filled with glass ionomer cement the resistance to fracture of the teeth decreased significantly compared with the acid etch resin technique. PMID- 1940751 TI - Determination and relationship of C-reactive protein in human dental pulps and in serum. AB - C-reactive protein (CRP), an acute phase protein synthesized by the liver, increases in serum as much as 3000 times above its normal level in response to acute inflammation. The purpose of this study was to determine whether CRP levels in dental pulps could be correlated with the histological disease status of the pulp and with systemic blood levels of CRP. Inflamed and necrotic pulps were extirpated during routine endodontic therapy. Normal pulps were removed from extracted, intact third molars. One half of each pulp specimen was placed in formalin for histological study; the other half was frozen for immunological study. A serum sample was obtained from each patient at the end of the dental visit. CRP levels were determined by the enzyme-linked immunosorbent assay. Pulps were categorized histologically as normal, inflamed, inflamed/necrotic, or necrotic. The correlation between CRP levels of pulp and serum was not significant. CRP levels of normal pulps differed significantly only from inflamed pulps (p less than 0.05, Dunnett). This increase in CRP appears to be a local phenomenon resulting from the interaction of CRP with various inflammatory mediators in the pulp. PMID- 1940750 TI - A comparison of thermoplasticized injectable gutta-percha obturation techniques. AB - This study compared the quality of obturation of high- and low-temperature thermoplasticized injectable gutta-percha techniques and standard lateral condensation. A new model system was developed to more closely simulate the clinical environment. All obturations were performed in this same model which allowed direct comparisons between the different techniques. The resultant mass of gutta-percha was visually examined and graded for each obturation. Statistical analysis of the results indicated that both thermoplasticized injectable techniques were significantly better than lateral condensation. There was no significant difference between either of the thermoplastic obturation techniques. PMID- 1940752 TI - A clinical evaluation of the Endocater--an electronic apex locator. AB - The purpose of this study was to evaluate the accuracy of an electronic apex locator, the Endocater, in determining the location of the apical constriction or cementodentinal junction (CDJ). Measurements made by the Endocater were also compared with the adjustments recommended by an experienced endodontist. A total of 69 teeth with 99 canals from nine patients were evaluated. The results indicated that the evaluator was 95.8% and the Endocater 67.7% accurate in positioning the probe within +/- 1.000 mm from the CDJ. Thirty-three canals or 34.4% appeared to be clinically acceptable radiographically and no adjustments were deemed necessary by the evaluator. There was a significant difference (p less than 0.003) between the evaluator's ability to adjust the electronically generated file length radiograph to acceptable clinical standards and the Endocater's ability to determine the location of the CDJ. A total of 59 canals (59.6%) of the electronically determined working lengths were beyond the CDJ (n = 99). In 27 canals, the tip of the probe was greater than 1 mm beyond the constriction. Without radiographs to confirm working lengths, many canals in this study would have been overinstrumented. Future research with electronic apex locators is needed before accepting the technique as a substitution for radiographic working length determination. PMID- 1940753 TI - A comparison of weights of debris extruded apically by conventional filing and Canal Master techniques. AB - Sixty extracted human teeth were divided into three groups of 20 each. Apically extruded debris and irrigant were collected, dried, and weighed by the following three instrumentation techniques: (a) group 1, filing 1 mm short of the foramen; (b) group 2, Canal Master instrumentation to the foramen; and (c) group 3, filing to the foramen (for a relative comparison). The results indicated that all three groups were significantly different from one another. Group 1 had the least amount of debris extruded. Of the two groups instrumented to the foramen, group 3 had twice as much debris extruded as group 2. An apical dentinal plug was frequently found in group 1 and was probably a major reason why this group had the least amount of extruded debris. The significance of this dentinal plug and possible indications for instrumentation to the foramen are discussed. PMID- 1940754 TI - The effect of essential oil type on the setting time of Grossman's sealer and Roth root canal cement. AB - Setting times were determined for mixtures consisting of the powder components of Grossman's sealer or Roth root canal cement with either eugenol, oil of pimento or oil of Melaleuca. The powder component of Grossman's sealer, when mixed with eugenol or oil of pimento, had a significantly shorter setting time than did the powder component of Grossman's sealer mixed with oil of Melaleuca or Roth root canal cement mixed with eugenol, oil of pimento, or oil of Melaleuca. PMID- 1940755 TI - Corrosion pattern of silver points in vivo. AB - The purpose of this study was to examine the electrochemical behavior of silver points in vivo. The apices of silver points removed from teeth with successful or failed endodontic treatments were subjected to complete surface characterization by small-area ESCA, scanning electron microscopy, and electron probe microanalyzer. Cross-sections of the points near the apex were examined with scanning electron microscopy and electron probe microanalyzer to identify the depth of corrosion involvement. According to the results, all silver points manifested evidence of corrosion attack. Electron probe microanalyzer showed no difference in the elemental distribution found on the points. ESCA analysis of the uppermost 5-nm point layer revealed the presence of N on silver points removed from failed treatments. The examination of cross-sections manifested deep S penetration in the bulk of the points removed from failed treatments. Considering the results of this study, no direct association seems to exist between the extent of the corrosion involvement and the prognosis of the treatment. Handling factors and the presence of bacteria are probably the parameters determining the outcome of a treatment. PMID- 1940756 TI - An new concept for removal of dental fluorosis stains. AB - Bleaching has been suggested by several authors in order to treat the unaesthetic aspect of dental fluorosis. Many results are, however, unsatisfactory. A different method, based on the structural characteristics of the fluorotic tooth and the organic and exogenous nature of fluorotic enamel stains, includes three principal stages: 1--enamel etching with 12% HCl in order to eliminate the posteruptive calcified layer that covers the fluorotic enamel surface and to denude the microcavities containing the organic elements; 2--application of pure manufactured sodium hypochlorite to remove these organic stains; and 3--filling the chemically opened microcavities with a light-cured dental adhesive to provide the tooth with a smooth and even surface and to prevent restaining. To improve the aesthetic aspect of intensely discolored teeth, it is possible to use a variety of tints available in several composite resin kits. Teeth with a rough enamel surface react more positively than ones with a smooth surface. The enamel adhesives provide better results than the amelo-dentinal ones. PMID- 1940757 TI - Retrospective study of tapered, smooth post systems in place for 10 years or more. AB - A total of 211 consecutive patients of a restorative dentist who received full mouth radiographs between October 1988 and March 1989 were screened for teeth treated endodontically at least 10 years earlier. In all, 51 patients had 138 teeth treated and restored by the authors. All involved teeth were restored with tapered smooth posts, cores with complete or 7/8 cast ferrules, and an onlay or cast precious metal crown (with or without veneering). No posts, splints, or bridges were loose, and only one crown was loose. There were nine failures in 138 teeth (6.5%)--three restorative, two endodontic, two root fractures, and two periodontal. When tapered smooth posts are used properly, retentive problems do not occur. PMID- 1940758 TI - Maxillary first molar with three palatal canals. AB - A case report is presented involving the endodontic treatment of a maxillary first molar with an unusual morphological variation of the palatal root. The palatal root canal system was characterized by a single canal orifice, a trifurcation on the apical one third of the root and three separate foramina. PMID- 1940759 TI - Development and crossmodal transfer of contextual control of emergent stimulus relations. AB - Six normally capable adults first learned three conditional relations in each of two prospective equivalence classes via match-to-sample training with figures as conditional (sample) and discriminative (comparison) stimuli. Then one trained conditional relation in each prospective class was brought under the control of contextual stimuli, two dictated nonsense syllables. Test performances indicated the emergence of untrained conditional relations, and therefore two equivalence classes, that were conditional on the contextual stimuli. These tests involved untrained combinations of contextual stimuli and stimuli in conditional relations, suggesting that the contextual stimuli functioned independently to control conditional relations rather than forming compound stimuli with samples and comparisons in training. Next, two novel figures were made equivalent to each of the original dictated contextual stimuli by match-to-sample training and testing. On subsequent tests, all subjects demonstrated transfer of conditional control of untrained conditional relations from the original auditory contextual stimuli to equivalent visual stimuli. These outcomes further supported the conclusion that the contextual stimuli exerted true conditional control over conditional relations in the equivalence classes and were not merely elements of compound stimuli. PMID- 1940760 TI - Transient effects of acquisition history on generalization in a matching-to sample task. AB - This study examined the role of learning history on the acquisition of a matching to-sample task. Twelve preschool children learned four stimulus classes through instructions, shaping, or imitation. After reaching criterion, the subjects were exposed to changed discrimination contingencies to determine how each learning history affected the acquisition of responses appropriate to the new contingencies. All subjects reached criterion on the new relations, although the subjects with a shaping history adapted slightly more quickly than those subjects with a history of instructions or imitation. Given sufficient exposure to changed contingencies, rule-driven insensitivity to contingencies was overcome by experience with consequences. This result may be specific to younger subjects, but it suggests that instructions can be used in education without creating insensitivity to contingencies. PMID- 1940761 TI - Preference for less frequent shock under fixed-interval schedules of electric shock presentation. AB - Lever pressing by 2 squirrel monkeys was maintained under fixed-interval 6-min and fixed-interval 2-min schedules of electric-shock presentation. Preference for these schedules was assessed during three experimental phases. In all phases, responses on one lever produced shock according to one or the other fixed interval schedule, and responses on a second, changeover, lever switched between schedules. The opportunity to change over was presented during separate choice periods (during which the fixed-interval schedules did not operate) that followed the first through fourth shocks in each schedule. If no changeover occurred during those choice periods, a changeover automatically occurred following the fifth shock. In Phase I, durations of the choice periods were fixed. In Phase II, the choice periods equaled a proportion of their respective fixed interval. During Phase III (completed with 1 monkey) a response on the changeover lever during a given choice period reinstated the most recent fixed interval, and a failure to respond resulted in a changeover. During each of these phases, distinct preferences developed for the 6-min schedule. These results suggest that the maintenance of lever pressing by fixed-interval presentation of electric shock may not be an example of positive reinforcement, and that the response maintaining characteristics of shock presentation may derive from other properties of the schedule. PMID- 1940762 TI - An experimental analysis of the cost of food in a closed economy. AB - Rats lived in individual chambers in which the only food available was delivered for lever pressing. During Stage I, a fixed number of presses was required for each food pellet. As this fixed ratio of presses per food pellet was increased daily, a rat's daily intake of food was reduced. During Stage II, the cost of a food pellet was increased by replacing each fixed ratio with its interval equivalent. Each interval was a rat's mean time between the first press of a ratio and the delivery of a pellet during Stage I. During Stage II, only two presses were every required for a food pellet: The first press initiated a delay and the second activated the pellet dispenser after that delay elapsed. Food intakes for the series of fixed ratios and a rat's series of delay equivalents were very similar when plotted as a function of delay, but not when plotted as a function of presses per pellet. Consequently, the fixed ratio reduced food intake because larger ratios increased delay to food from the first press of a ratio. Observations and an analysis of interresponse times further revealed that as the fixed ratio increased, and local as well as overall rate of food intake decreased, lever pressing became more stereotyped. Because this increased stereotypy resulted in greatly increased rates of lever pressing, delay to food was minimized, and perhaps more importantly, so too was the reduction of a rat's baseline daily intake. PMID- 1940763 TI - The interaction between stimulus and reinforcer control on remembering. AB - In a symbolic matching-to-sample task, 6 pigeons obtained food by pecking a red side key when the brighter of two white lights had been presented on the center key and by pecking a green side key when the dimmer of two white lights had been presented on the center key. Across Part 1 and Parts 6 to 10, the delay between sample-stimulus presentation and the availability of the choice keys was varied between 0 s and 25 s. Across Parts 1 to 5, the delay between the emission of a correct choice and the delivery of a reinforcer was varied between 0 s and 30 s. Although increasing both types of delay decreased stimulus discriminability, lengthening the stimulus-choice delay produced a greater decrement in choice accuracy than did lengthening the choice-reinforcer delay. Additionally, the relative reinforcer rate for correct choice was varied across both types of delay. The sensitivity of behavior to the distribution of reinforcers decreased as discriminability decreased under both procedures. These data are consistent with the view, based on the generalized matching law, that sample stimuli and reinforcers interact in their control over remembering. PMID- 1940764 TI - Effects of varying stimulus disparity and the reinforcer ratio in concurrent schedule and signal-detection procedures. AB - The present study measured the effects of stimulus and reinforcer variations on pigeons' behavior in two different choice procedures. Two intensities of white light were presented as the stimuli on the main key in a switching-key concurrent schedule and as the sample stimuli in a signal-detection procedure. Under both procedures, the scheduled rate of reinforcement was varied across conditions to produce various ratios of obtained reinforcement. These ratios were obtained for seven pairs of light intensities. In the concurrent schedules, the effects of reinforcer-ratio variations were positively correlated with the physical disparity between the two light intensities. In the signal-detection procedure, changes in the reinforcer ratio produced greater effects on performance when stimulus disparity was very low or very high compared to those found at intermediate levels of stimulus disparity. This discrepancy creates a dilemma for existing behavioral models of signal-detection performance. PMID- 1940765 TI - Stimulus generalization, discrimination learning, and peak shift in horses. AB - Using horses, we investigated three aspects of the stimulus control of lever pressing behavior: stimulus generalization, discrimination learning, and peak shift. Nine solid black circles, ranging in size from 0.5 in. to 4.5 in. (1.3 cm to 11.4 cm) served as stimuli. Each horse was shaped, using successive approximations, to press a rat lever with its lip in the presence of a positive stimulus, the 2.5-in. (6.4-cm) circle. Shaping proceeded quickly and was comparable to that of other laboratory organisms. After responding was maintained on a variable-interval 30-s schedule, stimulus generalization gradients were collected from 2 horses prior to discrimination training. During discrimination training, grain followed lever presses in the presence of a positive stimulus (a 2.5-in circle) and never followed lever presses in the presence of a negative stimulus (a 1.5-in. [3.8-cm] circle). Three horses met a criterion of zero responses to the negative stimulus in fewer than 15 sessions. Horses given stimulus generalization testing prior to discrimination training produced symmetrical gradients; horses given discrimination training prior to generalization testing produced asymmetrical gradients. The peak of these gradients shifted away from the negative stimulus. These results are consistent with discrimination, stimulus generalization, and peak-shift phenomena observed in other organisms. PMID- 1940766 TI - Adrenergic stimulation of substrate utilization by cardiac myocytes isolated from rainbow trout. AB - A method is described for the isolation of calcium-tolerant myocytes from adult rainbow trout. Isolated myocytes remain viable for at least 4 h in suspension as indicated by (1) maintenance of ATP, phosphocreatine (PCr) and glycogen levels; (2) maintenance of the integrity of cell membranes, shown by low rates of leakage of lactate dehydrogenase (LDH) to the medium and exclusion of Trypan Blue; (3) the ability to metabolize substrates; and (4) sensitivity to adrenergic agonists. CO2 production from both glucose and lactate was sensitive to adrenergic stimulation, with the following order of potency: isoproterenol greater than noradrenaline much greater than adrenaline greater than phenylephrine, which indicates the presence of beta 1-adrenoceptors. Myocytes isolated from trout acclimated to 20 degrees C in the summer were more sensitive to beta-adrenergic stimulation than myocytes isolated from trout acclimated to 9 degrees C in either summer or winter. In the absence of exogenous fuel, there was a net reduction in myocyte glycogen content and glycogenolysis was further stimulated by 10(-7) mmol l-1 noradrenaline. However, in the presence of exogenous fuel (either 5 mmol l-1 lactate or 5 mmol l-1 glucose), glycogen was 'spared' and noradrenaline stimulated glycogenolysis was apparently inhibited. PMID- 1940767 TI - Physiological significance of behavioral hypothermia in hypoxic toads (Bufo marinus). AB - We tested the hypotheses that hypoxic toads (Bufo marinus) in a thermal gradient would select a lower than normal temperature and that this behavioral response would be beneficial. Under normoxic conditions, selected body temperature was 24.2 +/- 3.6 degrees C. When inspired O2 was 10% or less, mean selected temperature decreased to 15.3 +/- 2.4 degrees C. The theoretical advantages of hypoxia-induced hypothermia we tested include (1) a reduction of oxygen uptake (VO2) by a Q10 effect; (2) increased arterial saturation (SaO2), (3) a decreased ventilatory response, and (4) a decreased stress response. Gas exchange, hematocrit, hemoglobin, SaO2, PaO2 and pH were measured at 25 degrees C (normal preferred temperature) and 15 degrees C (hypoxia preferred temperature) in toads breathing normoxic or hypoxic gas mixtures. During graded hypoxia at 15 degrees C, SaO2 was significantly increased and VO2 was significantly reduced compared with 25 degrees C. Graded hypoxia did not significantly affect VO2 at 25 degrees C, despite evidence for increased ventilation at that temperature (increased pH and respiratory exchange ratio, RE). At 15 degrees C, graded hypoxia had a significant effect on VO2 only at an inspired O2 of 4%. Increased RE with hypoxia was significant at 25 degrees C but not at 15 degrees C. Hematocrit and [hemoglobin] rose significantly during graded hypoxia at 25 degrees C but did not change at 15 degrees C. Toads exposed to 10% O2 (the value that elicits behavioral hypothermia) showed a significant respiratory alkalosis at 25 degrees C but not at 15 degrees C. Likewise, hypoxia caused a significant drop in SaO2 and PO2 at 25 degrees C. Cooling to 15 degrees C during hypoxia caused a significant rise in SaO2 but no change in PaO2. In conclusion, behavioral hypothermia is a beneficial response to hypoxia in Bufo marinus. PMID- 1940768 TI - K+ transport across the lamprey erythrocyte membrane: characteristics of a Ba(2+) and amiloride-sensitive pathway. AB - The characteristics of K+ transport in erythrocytes from the river lamprey (Lampetra fluviatilis) were investigated using standard radioisotope flux techniques. The cells were shown to have a ouabain-sensitive transport pathway that carried 43K+ and 86Rb+ into the cell at similar rates. Most of the ouabain resistant 43K+ and 86Rb+ influx was via a pathway that was insensitive to cotransport inhibitors and to the replacement of extracellular Cl- or Na+. This pathway showed a strong selectivity for 43K+ over 86Rb+. It was inhibited fully by Ba2+ (I50 approximately 2.8 mumol l-1), amiloride (I50 approximately 150 mumol l-1) and ethylisopropylamiloride (I50 approximately 3.3 mumol l-1) and less effectively by quinine and by the tetraethylammonium ion. Inhibition by Ba2+ took full effect within a few minutes whereas the full inhibitory effect of amiloride took more than 1 h to develop. Experiments with the membrane potential probe [14C]tetraphenylphosphonium ion gave results consistent with the lamprey erythrocyte membrane having a Ba(2+)-sensitive K+ conductance that was significantly greater than the membrane Na+ conductance and which gave rise to a marked dependence of the membrane potential on the extracellular K+ concentration. The rate constants for Ba(2+)-sensitive 43K+ and 86Rb+ influx decreased (proportionally) with increasing extracellular K+ concentration in a manner that was consistent with the transport being via a conductive pathway. The decrease was attributed to a depolarisation of the membrane (in response to the increasing extracellular K+ concentration) and a consequent decrease in the driving force for the conductive movement of 43K+ and 86Rb+ into the cells. Ba(2+)-sensitive 86Rb+ influx increased significantly with decreasing cell volume and with increasing intracellular pH (at a constant extracellular pH) but increased only slightly with increasing extracellular pH. The pathway operated normally in the complete absence of extracellular Ca2+ but its activity decreased in cells pretreated with ionomycin and EGTA; this suggests a role for intracellular Ca2+ in the operation of the pathway. PMID- 1940769 TI - The effect of N-ethylmaleimide on K+ and Cl- transport pathways in the lamprey erythrocyte membrane: activation of K+/Cl- cotransport. AB - The effect of the sulphydryl reagent N-ethylmaleimide on the K+ and Cl- transport pathways of the lamprey erythrocyte membrane was found to be quite complex. N Ethylmaleimide inhibited the Ba(2+)-sensitive pathway that mediates most of the ouabain-resistant influx of K+ into the cell under physiological conditions but stimulated a Cl(-)-dependent, B(2+)-resistant K+ transport pathway that was inhibited by compounds that inhibit Cl(-)-dependent K+ transport in the human erythrocyte. N-Ethylmaleimide (in most cases) reduced the total influx of Cl- into the lamprey erythrocyte but (in all cases) introduced a K(+)-dependent component into the measured Cl- uptake; this was explained in terms of N ethylmaleimide having inhibited the pathway primarily responsible for Cl- influx under physiological conditions but having stimulated a second, K(+)-dependent Cl- transport pathway. Although the magnitude of the K+ and Cl- fluxes stimulated by N-ethylmaleimide varied widely between cells from different lampreys, there was, in each individual case, a close similarity between the magnitude of the Cl(-) dependent K+ influx (calculated from the 86Rb+ uptake) and the K(+)-dependent Cl- influx; the mean value for the ratio of the former to the latter was 1.01 +/- 0.03 (N = 5). The results are therefore consistent with the sulphydryl reagent having activated a K+/Cl- cotransport system similar to that present in erythrocytes from many mammalian species. This raises the possibility that the lamprey red cell may be a uniquely suitable system in which to study the characteristics of Cl- transport by this pathway. PMID- 1940770 TI - Acid-base regulation and blood gas transport following exhaustive exercise in an agnathan, the sea lamprey Petromyzon marinus. AB - Exhaustive exercise in cannulated sea lampreys, Petromyzon marinus, resulted in a marked extracellular acidosis in the arterial blood which had both a respiratory and a metabolic component. Blood CO2 tension (PCO2) returned to control levels within an hour after exercise, but the metabolic acidosis had a somewhat longer time course and the extracellular pH (pHe) did not fully recover until the 4 h recovery sample. The magnitude and duration of the changes in both the plasma lactate concentration and the concentration of metabolic protons were very similar and the maximal proton deficit after exercise was, therefore, only 1.5 mequiv l-1. In contrast to the changes in pHe, there were no significant changes in the erythrocyte pH (pHi) following the exercise period. The regulation of pHi was apparently not adrenergically mediated, however, since addition of catecholamines to lamprey blood in vitro had no significant effect on pHi. In addition, the period of exhaustive exercise in vivo was not associated with any significant changes in the mean cellular hemoglobin concentration. The total carbon dioxide concentration in the arterial whole blood and true plasma were both significantly reduced after exercise, but the total carbon dioxide concentration within the erythrocytes was transiently increased. Finally, there was a marked decrease in the arterial PO2 immediately after exercise, which was associated with a significant reduction in the amount of oxygen bound to hemoglobin; however, within 30 min, these values had both returned to normal. The maintenance of pHi presumably contributes to the regulation of oxygen transport in lampreys and it may be particularly important during the brief period immediately after exercise when oxygen transport is clearly compromised. Although several studies have provided evidence that chloride/bicarbonate exchange limitations may exist in agnathan blood in vitro, the present results demonstrate that the characteristics of carbon dioxide transport and acid-base regulation after exercise in P. marinus are not markedly different from those in other lower vertebrates. PMID- 1940771 TI - Habituation of the ultrasound-induced acoustic startle response in flying crickets. AB - The ultrasound-induced negative phonotactic response of tethered, flying Australian field crickets habituates to repeated stimuli. Using the magnitude of the metathoracic leg's swing during a series of ultrasonic stimuli as a measure of habituation, we show that: (1) the response declines exponentially; (2) the response recovers spontaneously; (3) repeated trials produce more rapid and stronger habituation; (4) successive stimuli presented more rapidly produce more rapid and stronger habituation; (5) a weaker stimulus intensity produces more rapid and stronger habituation; (6) the habituation shows stimulus generalization (i.e. the response is similar for different ultrasonic frequencies); (7) a novel stimulus produces dishabituation; and (8) the effect of the dishabituating stimulus habituates after repeated trials. These findings place habituation of cricket negative phonotaxis in the context described for habituation in mammals. PMID- 1940772 TI - Influence of pregnancy on the oxygen affinity of red cells from the northern Pacific rattlesnake Crotalus viridis oreganus. PMID- 1940773 TI - Non-surgical therapy of gallstone disease--present situation. PMID- 1940774 TI - The polymerase chain reaction and its potential role in clinical diagnostics and research. AB - In-vitro amplification of deoxyribonucleic acid molecules by means of the polymerase chain reaction (PCR) must be regarded as the most important advance in the life sciences to take place during the last decade. Originally applied to the identification of mutations in well-known and fully sequenced human genes, its applications have now been extended to a wide variety of biological and medical disciplines, accompanied by significant technical improvements and sophisticated variations of the basic principle. Specialized molecular genetics laboratories were the first to employ this new method, and they still are in the process of extending its potential. Due to its unique properties, applications of PCR quickly spread to other areas of research, and numerous clinical studies have already employed PCR. The field is currently still expanding rapidly. PMID- 1940775 TI - Effect of apolipoprotein E polymorphism and XbaI polymorphism of apolipoprotein B on response to lovastatin treatment in familial and non-familial hypercholesterolaemia. AB - Despite the well-documented efficacy of lovastatin, a wide inter-individual variation in treatment responses has been observed. The aim of the present study was to investigate the possible roles of apolipoprotein E (apo E) phenotype and apolipoprotein B (apo B) XbaI genotype on this variation. The apo E phenotype was determined in 232 subjects (78 cases of familial hypercholesterolaemia [FH] and 154 cases of non-familial hypercholesterolaemia [non-FH]) and the apo B XbaI genotype was determined in 211 subjects (67 cases of FH, 144 cases of non-FH). Depending on their baseline total serum cholesterol levels, these patients used a starting dose of lovastatin of either 20 or 40 mg nightly. After 6 weeks of therapy, slightly but significantly smaller reductions in LDL-cholesterol were observed in patients with the E4/3 phenotype compared with those with the E3/3 phenotype in non-FH with lovastatin 20 mg (-20 vs. -28%; P = 0.043) and in total cholesterol in FH with lovastatin 40 mg (-23 vs. -27%; P = 0.023). No significant differences were found in non-FH patients starting with lovastatin, 40 mg. After doubling of the lovastatin doses, all treatment responses became similar among apo E phenotypes. Moreover, when all patients using lovastatin 40 mg either at 6 or 12 weeks were pooled (n = 224), no differences in treatment responses were observed between the E3/2, E3/3, E4/3 and E4/4 phenotypes. The apo B XbaI genotype did not affect the hypocholesterolaemic efficacy of lovastatin in any of the patient groups. Thus our results indicate that inter-individual variation in the treatment response to lovastatin in both familial and non-familial hypercholesterolaemia is mainly due to factors other than the apo E phenotype or apo B XbaI genotype. PMID- 1940777 TI - A 4-year prospective follow-up study of the role of alcohol in recurrences of atrial fibrillation. AB - Alcohol consumption data for 98 consecutive young and middle-aged patients presenting with new-onset atrial fibrillation (AF) were obtained on admission to hospital. The patients were subsequently followed up for 4 years in order to study the rate of recurrence of AF and its possible association with alcohol use. Neither recent alcohol intake, assessed as the amount of alcohol consumed during the week preceding AF, nor chronic alcohol use, assessed by the CAGE questionnaire, were significantly related to AF recurrence or development of chronic AF. This was also true for individuals with idiopathic AF. Left atrial diameter on echocardiography was significantly greater among the patients who developed chronic AF than among the others (P = 0.03). In this prospective study chronic alcohol abuse, as assessed by the CAGE questionnaire, was not associated with either subsequent recurrence of AF or development of chronic AF. PMID- 1940776 TI - A comparison between nicotinic acid and acipimox in hypertriglyceridaemia- effects on serum lipids, lipoproteins, glucose tolerance and tolerability. AB - Serum and lipoprotein lipid levels, oral glucose tolerance and side-effects were compared in an open cross-over study of 31 non-diabetic patients with hypertriglyceridaemia (type II B and IV) before and after 6 weeks of treatment with nicotinic acid (3 g daily) and acipimox (0.75 g daily), a new nicotinic acid like drug, respectively. Acipimox was about equally potent in reducing serum and VLDL lipid levels and in increasing HDL cholesterol levels. Acipimox had no significant negative effects on glucose metabolism measured by an oral glucose tolerance test compared with nicotinic acid, which decreased the late glucose tolerance as well as the area under the glucose curve (P less than 0.05 for the difference between the two treatments). The incidence and severity of flush or any other recorded side-effects was higher after nicotinic acid treatment than after acipimox. In addition, no effects on laboratory parameters such as liver enzymes and uric acid were seen after treatment with acipimox. The results of this study demonstrate that acipimox is a satisfactory alternative to nicotinic acid in patients with hypertriglyceridaemia. PMID- 1940778 TI - Cardiac rehabilitation--a cost analysis. AB - This economic evaluation is based on a 5-year follow-up study comparing a comprehensive cardiac rehabilitation programme with standard care after myocardial infarction (MI). The intervention group consisted of 147 non-selected MI patients aged less than 65 years, who were participating in a rehabilitation programme consisting of follow-up at a post-MI clinic, health education and physical training in out-patient groups. The control group consisted of a non selected MI-population aged less than 65 years (n = 158), who were receiving standard care. The rehabilitation programme did not increase the health-care costs of post-MI care, as the increase in cost due to participation in the programme was balanced by a decrease in readmissions for cardiovascular diseases. On average, the rehabilitated patient returned to work more frequently, resulting in decreased costs due to loss of production. The mean patient total cost of a 5 year MI follow-up was SEK 73,500 lower in the rehabilitated group. The outstanding winner of the rehabilitation programme was the Swedish National Health Insurance System (NHIS). It must be concluded that the comprehensive cardiac rehabilitation programme is a major strategy that leads to both lowered costs and positive health effects. The cardiac rehabilitation programme is therefore highly cost-effective. PMID- 1940779 TI - Cigarette smoking and urinary albumin excretion in insulin-treated diabetics without manifest nephropathy. AB - The frequency of microalbuminuria and glomerular hyperfiltration in insulin treated diabetics without manifest nephropathy was studied in 76 patients, 20-40 years of age and with a diabetes duration not exceeding 20 years. Clinical determinants of urinary albumin excretion (UAE) with regard to smoking were studied further in a sample of male diabetics (n = 49) without manifest nephropathy. All patients had an age-related glomerular filtration rate (GFR) exceeding -2 SD, and their diastolic blood pressure (DBP) did not exceed 90 mmHg. GFR was assessed by 51Cr-EDTA-clearance, and UAE was analysed using an immunochemical method. Diabetic smokers with a long diabetes duration (10-20 years) had a significantly higher UAE (39.5 +/- 2.4 mg 24 h-1 vs. 17.1 +/- 2.4 mg 24 h-1; P = 0.03), a higher mean arterial blood pressure (MAP) (97.9 +/- 7.5 mmHg vs. 91.5 +/- 6.3 mmHg; P = 0.02) and a higher frequency of micro-albuminuria (85.7% vs. 37%; P = 0.028) than non-smoking diabetics. Smokers with a short diabetes duration (0-10 years) had a significantly higher frequency of glomerular hyperfiltration (64% vs. 15%; P = 0.005) than non-smokers. The frequency of microalbuminuria or blood pressure did not differ significantly. In male non smokers (n = 35) UAE was positively correlated with HbAlc and negatively correlated with age of onset. In male smokers (n = 14) regression analysis showed that UAE was positively correlated only with duration of smoking. We conclude that smoking is associated with two accepted risk factors for nephropathy in insulin-treated diabetics, namely hyperfiltration and microalbuminuria. A positive linear relationship between smoking parameters and UAE in male diabetics also supports the view that smoking may increase the risk of nephropathy development in insulin-treated diabetics. PMID- 1940780 TI - Features of Sjogren's syndrome in patients with primary biliary cirrhosis. AB - Twenty-six consecutive patients with primary biliary cirrhosis (PBC) from northern Sweden were studied regarding the occurrence and features of Sjogren's syndrome (SS). In more than 50% of the patients the rose bengal dye test showed conjunctival and/or corneal staining. In six patients keratoconjunctivitis sicca (KCS) was present with positive rose bengal and Schirmer tests. In a further three patients only the results of the Schirmer tests were abnormal. Radiological findings of sialectasia were demonstrated in six patients, five of whom had KCS. Two of the seven patients who fulfilled our criteria for Sjogren's syndrome were HLA-B8 positive. A high prevalence of increased immune globulins and rheumatic factor was found, but this did not correlate with the presence of Sjogren's syndrome. Some features of Sjogren's syndrome were found in 73% of PBC patients, and keratoconjunctivitis sicca and/or sialectasia were found in 27% of PBC patients. This constitutes a high frequency of secondary manifestations of the liver disease. PMID- 1940781 TI - Extensor digitorum brevis in diabetic neuropathy: a controlled evaluation in diabetic patients aged 15-50 years. AB - A reduction in the bulk of the extensor digitorum brevis muscle (EDB) may be a sign of diabetic neuropathy. We devised a semi-quantitative scale (normal, reduced or absent) for assessing the bulk of the EDB muscle, and judged it to be a sign of neuropathy in 375 of 395 diabetic patients aged 15-50 years in the county of Umea, 79% of whom had Type 1 diabetes mellitus (DM), and in 100 healthy controls. Reduced or absent EDB was significantly more common in patients with Type 1 and Type 2 DM than in controls (44 and 48 vs. 12%; P less than 0.001). In patients with Type 1 DM, reduced or absent EDB was significantly correlated with age, longer duration of DM, smoking, dry feet, and foot ulcers, but not with fallen forefoot arch, hammer toes or callosities. Reduced or absent EDB was also associated with skin and nail lesions, including Melin's shin spots, purpura and yellow toenails, but not with necrobiosis. Sensory thresholds for vibration, perception and pain were all significantly elevated in Type 1 diabetic patients with impaired EDB, compared to Type 1 diabetics with normal EDB. In controls, impaired EDB was only significantly correlated with smoking. We conclude that the EDB test is easy to perform, and may be used to screen for neuropathy in Type 1 diabetic patients. PMID- 1940782 TI - Lack of association of migraine with coronary vasospasm. AB - Previous reports have found an association between coronary vasospasm and migraine. It has been speculated that migraine and variant angina might be manifestations of a generalized vasospastic disorder. To investigate this hypothesis, 74 patients with frequent attacks of migraine were studied using 24-h continuous ambulatory electrocardiography to identify the presence of coronary vasospasm. Control groups consisted of 19 patients with tension headaches, and 38 healthy individuals. All subjects were free of heart disease. One patient in the migraine group and one patient in the control group had symptomless episodes of ST-segment depression not indicative of coronary vasospasm. Our data do not support the hypothesis that migraine and variant angina are components of a generalized vasospastic disorder. PMID- 1940783 TI - Misoprostol-induced urinary incontinence. AB - In a young woman with rheumatoid arthritis misoprostol induced urinary incontinence. The urodynamic study described here revealed a deficiency in urethral resistance which may explain the phenomenon. This side-effect may be more common than expected, and misoprostol should be administered with caution to patients suffering from urinary stress incontinence. PMID- 1940784 TI - Rapidly fatal Addison's disease: three case reports. AB - Recently, three young individuals died unexpectedly outside hospital. Their past medical histories revealed complaints of weakness, anorexia and nausea, none of which had led to adequate medical examination. The present paper calls for vigilance when patients present with non-specific manifestations such as anorexia and weakness. Autopsies confirmed that the deaths were caused by adrenalitis, a diagnosis unsuspected at the time of death. The value of different post-mortem laboratory findings is discussed. PMID- 1940785 TI - Phenolic glycolipid-1 of Mycobacterium leprae binds complement component C3 in serum and mediates phagocytosis by human monocytes. AB - Previous studies from this laboratory have demonstrated that Mycobacterium leprae, an obligate intracellular bacterial parasite, enters human mononuclear phagocytes via complement receptors on these host cells and bacterium-bound C3. The present study investigates the role of M. leprae surface molecules in C3 fixation and phagocytosis. By enzyme-linked immunosorbent assay, C3 binds selectively to phenolic glycolipid-1 (PGL-1), a major surface molecule of the leprosy bacillus. C3 fixation to PGL-1 is serum concentration dependent and is abolished in heat-inactivated serum or serum containing ethylenediaminetetraacetic acid. C3 fixation is also abolished in serum containing ethyleneglycol-bis (beta-aminoethyl ether)N,N,N'-tetraacetic acid and MgCl2 indicating that isolated PGL-1 fixes C3 via the classical complement pathway. The capacity of PGL-1 to fix C3 is dependent upon its terminal trisaccharide since sequential removal of monosaccharide units of the trisaccharide results in a stepwise reduction in C3 fixation. Deacylation of PGL 1 also abolishes C3 fixation. C3 fixes to the trisaccharide of PGL-1 that is chemically linked to bovine serum albumin via the chemical carrier, 8 methoxycarbonyloctanol. PGL-1 mediates C3 fixation to polystyrene microspheres, and PGL-1 and C3 together mediate ingestion of polystyrene microspheres by human monocytes, wherein these inert test particles reside in membrane-bound phagosomes. Thus, complement receptors on mononuclear phagocytes, complement component C3, and PGL-1 comprise a three-component receptor-ligand-acceptor molecule system for mediating phagocytosis of M. leprae. PMID- 1940786 TI - Severe combined immunodeficiency (SCID) in man: B cell-negative (B-) SCID patients exhibit an irregular recombination pattern at the JH locus. AB - Human severe combined immunodeficiency (SCID) patients were analyzed by a polymerase chain reaction assay for their recombination capability at the DHQ52 JH region of the immunoglobulin heavy chain locus. Five patients with B cells (B+ SCID) exhibited a recombination pattern also observed in healthy persons. In contrast, six patients lacking B cells (B- SCID) showed a grossly altered rearrangement pattern characterized by the (partial) absence of regular DHQ52-JH recombinations and the presence of abnormal rearrangements. These events were caused by deletions surpassing the boundaries of immunoglobulin coding elements and thus resemble the pattern of deletional recombinations previously described in SCID mice. PMID- 1940787 TI - Lysozyme is an inducible marker of macrophage activation in murine tissues as demonstrated by in situ hybridization. AB - This study demonstrates the induction of lysozyme mRNA expression in situ in tissue macrophages (M phi) of mice following in vivo stimulation. The resting resident tissue M phi of most tissues do not contain enough lysozyme mRNA to be detected by in situ hybridization using 35S-labeled RNA probes. Following Bacille Calmette Guerin or Plasmodium yoelli infection, however, M phi recruited to liver and spleen hybridize strongly to the lysozyme probe. Within 24 h of infection, cells found in the marginal zone of the spleen begin to produce lysozyme mRNA. This response is also evoked by a noninfectious agent (intravenously injected sheep erythrocytes), and is possibly the result of an early phagocytic interaction. Later in the infection, other cells in the red and white pulp of the spleen, and cells in granulomas in the liver, become lysozyme-positive. Kupffer cells are rarely lysozyme-positive. Lysozyme mRNA levels in liver granulomas remain relatively constant during the infection, and lysozyme is produced by most granuloma cells. This contrasts with tumor necrosis factor alpha (TNF alpha) mRNA, which is produced by fewer cells in the granuloma, and which can be massively induced by lipopolysaccharide administration. The production of lysozyme, previously considered a constitutive function of M phi, is therefore an indicator of M phi activation in vivo, where immunologically specific and nonspecific stimuli both stimulate lysozyme production at high levels in subpopulations of cells occupying discrete anatomical locations. PMID- 1940788 TI - On the nature of peptides involved in T cell alloreactivity. AB - The strong reaction of T cells against foreign major histocompatibility complex (MHC) antigens, commonly termed "alloreactivity", is not only a nuisance for clinical organ transplantation; it also remains a puzzling question for immunologists. By making use of recent technical developments, alloreactive T cells nominally directed against a mutation in a single MHC class I molecule were found to fall into several major categories. One is recognizing peptides whose occurrence is dependent on one particular MHC allele, another is recognizing peptides supported by several MHC alleles, and a third is recognizing peptides occurring independently of MHC alleles. In a fourth category, the binding to MHC of any of a broad range of peptides appears sufficient. In addition, there are T cells for which no peptide involvement could be detected at all. Even within these categories, the heterogeneity of T cells is considerable: among 16 Kb reactive T cells analyzed, 15 different modes of reactions were found. PMID- 1940789 TI - The Salmonella typhimurium locus mviA regulates virulence in Itys but not Ityr mice: functional mviA results in avirulence; mutant (nonfunctional) mviA results in virulence. AB - The virulent Salmonella typhimurium strain WB600 carries the mviA allele of the gene mouse virulence A. As shown here, the virulent phenotype of WB600 is the result of a nonfunctional mviA gene. As compared to the functional allele mviA+, mviA increases virulence in Itys mice, but not in Ityr mice. A specific BglII site, mviA4185, between osmZ and galU, located at approximately 35 min on the salmonella chromosome, was within mviA. Insertion of an antibiotic cassette in the mviA4185 site of mviA+ or the homologous mviA4093 site of mviA DNA resulted in virulence when either cassette was recombined into the chromosome. When mviA and mviA+ were both expressed in the same strain with one carried in the chromosome and the other on a plasmid, avirulence was dominant. Replacement of the mviA allele of strain WB600 using P22 transductions of linked antibiotic cassettes cloned into the chromosome of virulent S. typhimurium strains (SR-11, TML, SL1344, C5, ATCC14028, W118-2, and WB600) showed that all but WB600 contained the avirulent mviA+ allele. Southern hybridizations provided no evidence for a second mviA allele anywhere in the genome of the six non-WB600 strains. PMID- 1940790 TI - Molecular definition of a polymorphic antigen (LA45) of free HLA-A and -B heavy chains found on the surfaces of activated B and T cells. AB - A monomoprhic monoclonal antibody (LA45 antibody) reactive with "a new activation induced surface structure on human T lymphocytes" (LA45 antigen) that resembled free class I heavy chains has recently been described (Schnabl, E., H. Stockinger, O. Majdic, H. Gaugitsch, I.J.D. Lindley, D. Maurer, A. Hajek Rosenmayr, and W. Knapp. 1990. J. Exp. Med. 171:1431). This antibody was used to clone a class I-like heavy chain (LA45 gene) from the HUT 102 tumor cell, which paradoxically did not give rise to the LA45 antigen on transfection into monkey COS cells. We show here that the LA45 gene is HLA-Aw66.2, a previously uncharacterized allele of the HLA-A locus. The previously determined LA45 sequence differs from that of HLA-Aw66.2, from HUT 102, and the CR-B B cell line derived from the same individual as HUT 102 by substitution of tryptophan for serine at position 4 in the alpha 1 domain. Transfection of HLA-Aw66.2, and of a mutant of this gene with serine 4 substituted for tryptophan, into a human B cell line (C1R) both resulted in expression of the LA45 epitope. Furthermore, we find expression of the LA45 epitope on Epstein Barr virus-transformed B cell lines as well as lectin-activated T cells, but not on long-term T cell lines or unstimulated peripheral blood T cells. The specificity of the LA45 antibody is polymorphic and the presence of the LA45 epitope is precisely correlated with the sequence arginine, asparagine (RN) at residues 62 and 63 of the helix of the alpha 1 domain. The LA45 epitope is broadly distributed, being associated with half the alleles of both HLA-A and -B loci but none of the HLA-C locus. All the results are consistent with the presence of pools of free HLA-A and -B heavy chains at the surfaces of certain cell types but not others. Such molecules are probably responsible for the HLA-associated class I alloantigens of lectin activated T cells. We hypothesize the free heavy chains result from dissociation of beta 2-microglobulin from subpopulations of empty HLA-A,B molecules, or molecules with weakly bound peptides, that vary in size depending on cellular activation and peptide supply. PMID- 1940791 TI - COOH terminus of membrane IgM is essential for an antigen-specific induction of some but not all early activation events in mature B cells. AB - Transfectants of mature B cell lines that bind phosphorylcholine were made in order to understand the role of the COOH terminus of the mu chain of membrane IgM (mIgM) in generation of antigen-specific signals. A chimeric receptor (I-A alpha tail) was constructed by replacing 40 amino acids from the mu COOH terminus with that of major histocompatibility complex class II I-A alpha chain. The effect of wild-type and chimeric tails were studied on representative immediate-early antigen-specific signals. The I-A alpha tail hybrid, but not the wild-type receptor, was defective in antigen-driven Ca2+ mobilization, although it could effectively endocytose ligand-receptor complexes. Signal(s) transduced through the wild-type receptor led to transient induction of selected immediate-early gene messages (Egr-1, c-fos, Jun) above basal levels. However, the signal(s) generated after crosslinking of the I-A alpha tail receptor either showed no effect (c-fos) or actually repressed basal level expression of Egr-1 and Jun. Thus, we have established that receptor-mediated endocytosis can be distinguished from other early events associated with B cell activation, based on their differential dependence upon the structural fidelity of the COOH-terminal sequence of mIgM. PMID- 1940792 TI - Enhanced binding of peptide antigen to purified class II major histocompatibility glycoproteins at acidic pH. AB - Helper T lymphocytes recognize peptide antigens stably associated with class II major histocompatibility complex (MHC) glycoproteins on the surface of antigen presenting cells and serve to regulate a wide variety of immune responses. A previous study from our laboratory had demonstrated that the functional association of various peptide antigens with the antigen-presenting cell membrane was increased at pH 5 as compared to pH 7, consistent with the potential role of acidic endosomal compartments in antigen processing. The mechanism for this effect was not determined. In the present study, assays using purified class II glycoprotein were used to further define this mechanism. The potential requirement for pH-dependent interactions involving non-MHC membrane components was excluded in functional assays with purified class II reconstituted in artificial membranes containing only neutral phospholipids and cholesterol. The association of HEL(104-120) with I-Ed, and OVA(323-339) with I-Ad, was increased at pH 5, as measured by activation of specific T cell hybridomas. An enzyme immunoassay was developed to measure the binding of biotin-labeled peptides to purified class II in detergent micelles. The pH dependence of binding paralleled our previous functional results. Optimum binding of biotin-HEL(104-120) to I-Ed was observed at pH approximately 4.5, whereas maximum binding of biotin-Myo(106 118) to I-Ad occurred at pH approximately 5.5. The latter peptide also bound weakly to I-Ed, but with a pH dependence similar to that observed using HEL(104 120). Further experiments with biotin-HEL(104-120)/I-Ed indicated that both the apparent affinity and the apparent concentration of peptide-binding sites are increased as hydrogen ion concentration is increased from pH 7 to pH 5. The effect of pH in this range was largely reversible and was not associated with a change in peptide dissociation that could be measured with our assay system. Binding was not inhibited in the presence of 1.5 M NaCl, suggesting that electrostatic interactions between HEL(104-120) and I-Ed are not essential for binding. It is proposed that protonation of a critical group(s) in the class II molecule regulates its capacity to form stable complexes with peptide. However, this effect alone does not fully account for the rapid kinetics of peptide binding observed in experiments with intact antigen-presenting cells. PMID- 1940793 TI - Reduction of disulfide bonds during antigen processing: evidence from a thiol dependent insulin determinant. AB - Previous studies have demonstrated that insulin, like other protein antigens, requires processing in metabolically active antigen-presenting cells (APC) before it can be recognized by class II-restricted T lymphocytes. Unlike many other proteins, insulin peptides of minimal size retain the requirement for antigen processing. We demonstrate that this requirement can be bypassed by incubation of insulin with reducing agents in the presence of aldehyde-fixed APC. Fixed APC treated in this way were able to stimulate I-Ab- and I-Ad-restricted T cell hybridomas. Data are presented that demonstrate that cloned and polyclonal T cells recognize a determinant within the NH2-terminal 14 residues of the beef insulin A chain with no requirement for B chain residues. The common feature among peptides capable of stimulating these cells in the presence of live APC is the chemical form of the cysteine thiol groups. Those forms that produce free thiols upon reduction are active, whereas those with irreversibly protected sulfhydryls are not. Functional experiments with fixed APC and competition binding experiments with purified I-Ad indicate that only A chain peptides with free thiols are able to stably associate with the peptide-binding site on class II in a form that is recognized by specific T cells. Our findings indicate that reduction of disulfide bonds is both necessary and sufficient for presentation of insulin to a major population of class II-restricted T cells. The results provide strong support for the hypothesis that protein disulfides can be reduced during physiologic antigen processing. PMID- 1940794 TI - T cell receptor V-segment frequencies in peripheral blood T cells correlate with human leukocyte antigen type. AB - We compared T cell receptor (TCR) V-segment frequencies in human leukocyte antigen (HLA) identical siblings to sibling pairs who differ at one or both HLA haplotypes using four V beta-specific and one V alpha-specific monoclonal antibody. In every one of nine families HLA-identical sibs had the most similar patterns of V-segment frequencies in their peripheral blood, whereas totally mismatched sibs were, in general, the most dissimilar; HLA haploidentical sibs tended to be intermediate between the two groups. The degree of similarity among HLA-identical sibs was comparable to that observed among three pairs of identical twins suggesting that HLA is the major genetic component influencing TCR V segment frequency. Consistent with this observation, it was found that the frequency of T cells expressing particular V beta segments was skewed towards either CD4+ or CD8+ cells indicating that T cells expressing some V beta genes may be positively selected primarily by class I or class II major histocompatibility complex proteins. Finally, it was observed that individuals who express the HLA class I specificity, B38, tend to express high levels of V alpha 2.3+ cells among their CD8+ T cells. These observations represent definitive proof that human V-segment frequencies are profoundly influenced by the HLA complex. PMID- 1940796 TI - Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice. AB - Antigens and infectious agents that stimulate interferon alpha(IFN-alpha) production in mice induce antibody responses that are predominantly of the immunoglobulin (Ig)G2a isotype and contain little or no IgE. This suggested the possibility that IFN-alpha might have a role in directing Ig isotype selection. Consistent with this possibility, we have found that injection of mice with recombinant mouse IFN-alpha suppresses IgE secretion, enhances IgG2a secretion, and has no independent effect on IgG1 secretion in mice stimulated with a foreign anti-IgD antibody. Injection of mice with polyinosinic acid.polycytidylic acid (poly I.C), an inducer of macrophage IFN-alpha production, also suppresses the anti-IgD antibody-induced IgE response and stimulates the IgG2a response; these effects are blocked by a sheep antibody that neutralizes mouse IFN-alpha/beta. Both recombinant IFN-alpha and poly I.C have maximum IgE suppressive and IgG2a stimulatory effects when injected early in the anti-IgD antibody-induced immune response. Addition of IFN-alpha to mouse B cells cultured with lipopolysaccharide (LPS) + interleukin 4 (IL-4) suppresses both IgG1 and IgE production, but much less potently than IFN-gamma. IFN-alpha suppresses anti-IgD antibody-induced increases in the level of splenic IL-4 mRNA, but enhances the anti-IgD antibody induced increase in the splenic level of IFN-gamma mRNA. These results are consistent with the effect of IFN-alpha on Ig isotype expression in mice, as IL-4 stimulates IgE and suppresses IgG2a secretion while IFN-gamma exerts opposite effects. These observations suggest that antigen presenting cells, by secreting IFN-alpha early in the course of an immune response, can influence the nature of that response both through direct effects on B cells and by influencing the differentiation of T cells. PMID- 1940795 TI - Regulation of cytokine production in the human thymus: epidermal growth factor and transforming growth factor alpha regulate mRNA levels of interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6 in human thymic epithelial cells at a post transcriptional level. AB - Human thymic epithelial (TE) cells produce interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6, cytokines that are important for thymocyte proliferation. The mRNAs for these cytokines are short-lived and are inducible by multiple stimuli. Thus, the steady-state levels for IL-1 and IL-6 mRNAs are critical in establishing the final cytokine protein levels. In this study we have evaluated the effect of epidermal growth factor (EGF), a growth factor for TE cells, and its homologue transforming growth factor alpha (TGF-alpha), on primary cultures of normal human TE cells for the levels of IL-1 alpha, IL-1 beta, IL-6, and TGF alpha mRNA. We showed that TE cells expressed EGF receptors (EGF-R) in vitro and in vivo, and that treatment of TE cells with EGF or TGF-alpha increased IL-1 and IL-6 biological activity and mRNA levels for IL-1 alpha, IL-1 beta, and IL-6. Neither EGF nor TGF-alpha increased transcription rates of IL-1 alpha, IL-1 beta, and IL-6 genes, but rather both EGF and TGF-alpha increased cytokine mRNA stability. By indirect immunofluorescence assay, TGF-alpha was localized in medullary TE cells and thymic Hassall's bodies while EGF-R was localized to TE cells throughout the thymus. Thus, TGF-alpha and EGF are critical regulatory molecules for production of TE cell-derived cytokines within the thymus and may function as key modulators of human T cell development in vivo. PMID- 1940797 TI - Selection of antigen-specific, idiotype-positive B cells in transgenic mice expressing a rearranged M167-mu heavy chain gene. AB - Flow cytometric analysis of antigen-specific, idiotype-positive (id+), B cell development in transgenic mice expressing a rearranged M167-mu gene shows that large numbers of phosphocholine (PC)-specific, M167-id+ B cells develop in the spleen and bone marrow of these mice. Random rearrangement of endogenous V kappa genes, in the absence of a subsequent receptor-driven selection, should give rise to equal numbers of T15- and M167-id+ B cells. The observed 100-500-fold amplification of M167-id+ B cells expressing an endogenous encoded V kappa 24]kappa 5 light chain in association with the M167 VH1-id transgene product appears to be an antigen driven, receptor-mediated process, since no amplification of non-PC-binding M167 VH1/V kappa 22, T15-id+ B cells occurs in these mu-only transgenic mice. The selection and amplification of antigen specific, M167-id+ B cells requires surface expression of the mu transgene product; thus, no enhancement of M167-id+ B cells occurs in the M167 mu delta mem transgenic mice, which cannot insert the mu transgene product into the B cell membrane. Surprisingly, no selection of PC-specific B cells occurs in M167-kappa transgenic mice although large numbers of B cells expressing a crossreactive M167 id are present in the spleen and bone marrow of these mice. The failure to develop detectable numbers of M167-id+, PC-specific B cells in M167-kappa transgenic mice may be due to a very low frequency of M167-VH-region formation during endogenous rearrangement of VH1 to D-JH segments. The somatic generation of the M167 version of a rearranged VH1 gene may occur in less than one of every 10(5) bone marrow B cells, and a 500-fold amplification of this M167-Id+ B cell would not be detectable by flow cytometry even though the anti-PC antibody produced by these B cells is detectable in the serum of M167-kappa-transgenic mice after immunization with PC. PMID- 1940798 TI - Recombinant Pfs25 protein of Plasmodium falciparum elicits malaria transmission blocking immunity in experimental animals. AB - Pfs25 is a sexual stage antigen of Plasmodium falciparum that is expressed on the surface of zygote and ookinete forms of the parasite. Monoclonal antibodies directed against native Pfs25 can block completely the development of P. falciparum oocysts in the midgut of the mosquito vector. Thus, this 25-kD protein is a potential vaccine candidate for eliciting transmission-blocking immunity in inhabitants of malaria endemic regions. We have synthesized, by secretion from yeast, a polypeptide analogue of Pfs25 that reacts with conformation-dependent monoclonal antibodies, and elicits transmission-blocking antibodies when used to immunize mice and monkeys in conjunction with a muramyl tripeptide adjuvant. Our results suggest the further evaluation of recombinant DNA-derived Pfs25 in transmission-blocking vaccination studies in humans. PMID- 1940799 TI - Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. AB - In the present study we demonstrate that human monocytes activated by lipopolysaccharides (LPS) were able to produce high levels of interleukin 10 (IL 10), previously designated cytokine synthesis inhibitory factor (CSIF), in a dose dependent fashion. IL-10 was detectable 7 h after activation of the monocytes and maximal levels of IL-10 production were observed after 24-48 h. These kinetics indicated that the production of IL-10 by human monocytes was relatively late as compared to the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and granulocyte colony-stimulating factor (G-CSF), which were all secreted at high levels 4-8 h after activation. The production of IL-10 by LPS activated monocytes was, similar to that of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, inhibited by IL-4. Furthermore we demonstrate here that IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level. Viral-IL-10, which has similar biological activities on human cells, also inhibited the production of TNF alpha and GM-CSF by monocytes following LPS activation. Activation of monocytes by LPS in the presence of neutralizing anti-IL-10 monoclonal antibodies resulted in the production of higher amounts of cytokines relative to LPS treatment alone, indicating that endogenously produced IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL 6, IL-8, TNF alpha, GM-CSF, and G-CSF. In addition, IL-10 had autoregulatory effects since it strongly inhibited IL-10 mRNA synthesis in LPS activated monocytes. Furthermore, endogenously produced IL-10 was found to be responsible for the reduction in class II major histocompatibility complex (MHC) expression following activation of monocytes with LPS. Taken together our results indicate that IL-10 has important regulatory effects on immunological and inflammatory responses because of its capacity to downregulate class II MHC expression and to inhibit the production of proinflammatory cytokines by monocytes. PMID- 1940800 TI - Perforin-expressing granulated metrial gland cells in murine deciduoma. AB - It has previously been shown that granulated metrial gland (GMG) cells of the pregnant uterus express abundant quantities of the lymphocyte pore-forming protein, perforin. No perforin was present before implantation of the embryo, but large numbers of perforin-producing GMG cells were observed after implantation, which coincides with decidualization of the uterus. The possible source of the activation factors responsible for perforin gene induction in GMG cells was studied here with the pseudopregnancy model, in which cervical stimulation of mice during estrus leads to a series of hormonal changes resembling those seen in pregnancy, but in the absence of an embryo. Subsequent stimulation of the uterus of pseudopregnant mice with oil causes the stimulated portion of the endometrium to differentiate into decidual tissue. Perforin-containing GMG cells were in fact present in the deciduomata, but not in adjacent nondecidualized tissues of the same mice. These results suggest that maternal factors associated with decidual tissue are responsible for the local expression of perforin in GMG cells. PMID- 1940801 TI - Human autoantibody to RNA polymerase I transcription factor hUBF. Molecular identity of nucleolus organizer region autoantigen NOR-90 and ribosomal RNA transcription upstream binding factor. AB - In dividing eukaryotic cells, nucleoli disperse before mitosis and reform in daughter cells at sites of ribosomal RNA (rRNA) gene clusters that are at the secondary constrictions of chromosomes, called nucleolus organizer regions (NORs). In this study, cDNA clones for a NOR autoantigen (NOR-90) were selected using a specific human autoantibody probe and were subsequently identified to encode an alternative form of the reported human upstream binding factor (hUBF). Results from immunoprecipitation showed that anti-NOR-90 antibodies recognized both forms of hUBF/NOR-90. Our data therefore showed that UBF, a critical factor in the regulation of rRNA transcription, was tightly bound to NOR during mitosis even when rRNA synthesis was thought to be minimal. Furthermore, we identified a nucleolar transcription factor as a novel target for human autoimmune response. PMID- 1940803 TI - Identification of C3 beta chain as the human serum eosinophil cytotoxicity inhibitor. AB - An eosinophil cytotoxicity inhibitor (ECI) was purified from serum of a human subject with severe allergic dermatitis. Molecular weight of the isolated polypeptide (75,000) and its NH2-terminal amino acid sequence identified it as the beta chain of the C3 complement component (apparently free, but perhaps attached to very small fragments of the alpha chain). Free beta chain, prepared from normal plasma by reduction of C3, inhibited both eosinophil cytotoxicity and neutrophil adherence functions, with half-maximal activity at approximately 250 ng/ml. Apparently free C3 beta chain was detected in certain human biological fluids associated with inflammation; the presence of C3 beta chain correlated with ECI activity. This evidence demonstrates a potential role for free C3 beta chain as a suppressor of eosinophil and neutrophil functions in inflammation. PMID- 1940802 TI - High frequency of t(14;18) translocation in salivary gland lymphomas from Sjogren's syndrome patients. AB - Sjogren's syndrome (SS) is a chronic autoimmune disorder characterized by lymphocytic infiltration of the salivary and lacrimal glands. These patients have a markedly increased frequency of developing non-Hodgkin's lymphoma in their salivary glands and cervical lymph nodes. Translocations of proto-oncogene bcl-2 t(14;18) were observed in five of seven SS-associated lymphomas by Southern blot analysis. Using primers specific for chromosomes 14 and 18, translocation of the proto-oncogene bcl-2 was detected by polymerase chain reaction (PCR) in all five lymphomas positive by Southern blot analysis. Among SS patients lacking clinical evidence of coexistent lymphoma, no bcl-2 translocations were detected in 50 consecutive salivary gland biopsies. Of particular interest, pre-lymphoma biopsies were available from the seven SS patients who subsequently developed lymphoma and these DNA samples lacked detectable t(14;18) translocations even though they exhibited oligoclonal rearrangements of their immunoglobulin genes. We conclude that the great sensitivity of PCR can help us in detecting early onset of lymphoma in SS patients and aid in understanding the transition from autoimmunity to lymphoma. PMID- 1940804 TI - Characterization and clonal distribution of four alleles of the speA gene encoding pyrogenic exotoxin A (scarlet fever toxin) in Streptococcus pyogenes. AB - Streptococcus pyogenes strains producing pyrogenic exotoxin A (scarlet fever toxin) have recently caused episodes of streptococcal toxic-shock-like syndrome (TSLS). We exploited knowledge of genetic diversity and relationships among exotoxin A-producing patient strains provided by multilocus enzyme electrophoresis to select strains for comparative sequencing of toxin genes. Our analysis identified four alleles of speA in natural populations, one of which (speA1) occurs in many distinct clonal lineages and is probably old. Two other alleles (speA2 and speA3), characterized solely by single amino acid substitutions, were each identified in single clones that together have caused the majority of TSLS episodes. It is unlikely that these alleles have had a long association with S. pyogenes clones. A fourth allele (speA4) also is present in a single phylogenetic lineage and is 9% divergent from the other three toxin alleles. An absence of synonomous (silent) nucleotide changes in speA2 and speA3 is unusual and suggests that the allelic variation is not selectively neutral, which implies that the toxins are not functionally equivalent. These results may be important in helping to understand the recent increase in frequency and severity of disease caused by S. pyogenes. PMID- 1940805 TI - Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels. AB - Vascular permeability factor (VPF) is a highly conserved 34-42-kD protein secreted by many tumor cells. Among the most potent vascular permeability enhancing factors known, VPF is also a selective vascular endothelial cell mitogen, and therefore has been called vascular endothelial cell growth factor (VEGF). Our goal was to define the cellular sites of VPF (VEGF) synthesis and accumulation in tumors in vivo. Immunohistochemical studies were performed on solid and ascites guinea pig line 1 and line 10 bile duct carcinomas using antibodies directed against peptides synthesized to represent the NH2-terminal and internal sequences of VPF. These antibodies stained tumor cells and, uniformly and most intensely, the endothelium of immediately adjacent blood vessels, both preexisting and those newly induced by tumor angiogenesis. A similar pattern of VPF staining was observed in autochthonous human lymphoma. In situ hybridization demonstrated VPF mRNA in nearly all line 10 tumor cells but not in tumor blood vessels, indicating that immunohistochemical labeling of tumor vessels with antibodies to VPF peptides reflects uptake of VPF, not endogenous synthesis. VPF protein staining was evident in adjacent preexisting venules and small veins as early as 5 h after tumor transplant and plateaued at maximally intense levels in newly induced tumor vessels by approximately 5 d. VPF-stained vessels were also hyperpermeable to macromolecules as judged by their capacity to accumulate circulating colloidal carbon. In contrast, vessels more than approximately 0.5 mm distant from tumors were not hyperpermeable and did not exhibit immunohistochemical staining for VPF. Vessel staining disappeared within 24-48 h of tumor rejection. These studies indicate that VPF is synthesized by tumor cells in vivo and accumulates in nearby blood vessels, its target of action. Because leaky tumor vessels initiate a cascade of events, which include plasma extravasation and which lead ultimately to angiogenesis and tumor stroma formation, VPF may have a pivotal role in promoting tumor growth. Also, VPF immunostaining provides a new marker for tumor blood vessels that may be exploitable for tumor imaging or therapy. PMID- 1940806 TI - "Increased frequency of T cell receptor V alpha 12.1 expression on CD8+ T cells: evidence that V alpha participates in shaping the peripheral T cell repertoire". PMID- 1940808 TI - Practice-based research. PMID- 1940807 TI - The V beta 17+ T cell repertoire: skewed J beta usage after thymic selection; dissimilar CDR3s in CD4+ versus CD8+ cells. AB - To ascertain how the actual repertoire of T cell receptors (TCRs) deviates from the theoretical, we have generated a large number of junctional region sequences from TCRs carrying the V beta 17 variable region. The greater than 600 sequences analyzed represent transcripts from nine different cell populations, permitting several comparisons: transcripts from an expressed vs. a non-expressed V beta 17 allele, those from E+ vs. E- mice, transcripts from immature vs. mature thymocytes, those from thymic vs. peripheral T cells, and those from CD4+ vs. CD8+ cells. These comparisons have allowed us to distinguish between the influence of molecular events involved in TCR gene rearrangement and that of various selection events that shape the T cell repertoire. Our most striking findings are: (a) that J beta usage is markedly skewed, partly due to recombination mechanics and partly due to selection forces: in particular, those mediated by the class II E molecule in the thymus; and (b) that TCRs on CD4+ and CD8+ cells show intriguing dissimilarities. In addition, we present evidence that N nucleotide additions occur with clear biases, probably due to idiosyncrasies of the recombination enzymes, and provide arguments that TCR and immunoglobulin CDR3s have distinct structures. PMID- 1940809 TI - Environmental health resources. PMID- 1940810 TI - Visiting professor series. PMID- 1940811 TI - Laboratory testing in the 1990s. PMID- 1940812 TI - Factors related to accuracy in office cholesterol testing. Iowa Academy of Family Physicians Research Network. AB - BACKGROUND: There has been growing interest in the performance of diagnostic testing in physician office laboratories (POLs). Since the measurement of cholesterol is a well-defined and standardized laboratory test, it was selected to assess factors related to test accuracy in POLs. METHODS: One hundred thirty one family practice offices were eligible to participate in the survey. Each was mailed a cholesterol specimen with a standardized value in October 1988. The laboratory characteristics of those POLs with results that were within 10% of the true specimen value were compared with those with results that were greater than 10% in error. RESULTS: Of the 131 POLs, 122 returned an answer for the unknown specimen. Ninety-eight (80%) were within 10% of the true value, and 114 (93%) were within 15%. Factors that were related to lower error rates (more likely to be within 10% total error) were whether the laboratory performed more than 25 laboratory tests per day, participated in a proficiency testing program, and ran daily quality controls, as well as the type of instrument the laboratory used. CONCLUSIONS: Overall performance of the POLs compared favorably with reference laboratories; however, running controls and participating in a proficiency testing program may further improve POL test accuracy. PMID- 1940813 TI - Effect of the white blood count on the clinical management of the febrile infant. AB - BACKGROUND: The white blood count is commonly used in the evaluation of the febrile infant without a focal source of infection. This study describes the physician's use of diagnostic tests in this clinical situation and also evaluates the effect of an elevated white blood count (WBC) on diagnostic test ordering and patient management. METHODS: A case scenario describing a febrile infant was mailed to all 294 pediatric, family, general, and emergency physician members of the Academy of Medicine of Cleveland. Questions about test ordering and case management were asked, both before and after the patient's WBC was known. Physicians were randomly assigned to receive a case scenario with either a normal or an elevated WBC. RESULTS: Of the 294 physicians contracted, 196 (67%) returned usable questionnaires. Physicians ordered an average of 1.4 tests in the initial management of the case, for an average cost of $82. Emergency physicians ordered more tests than other physicians (2.4 vs 1.2 tests, P = .001). Once the WBC was known, physicians in the high WBC group ordered more additional tests than the normal WBC group (0.89 vs 0.33 tests, P less than .001), and were more likely to change to a more aggressive therapeutic management strategy (P less than .001). CONCLUSIONS: The cost of physician-ordered laboratory testing is significant for the clinical scenario of a febrile infant without a localizing source. An elevated WBC affects physician management by causing more tests to be ordered and by influencing some physicians to choose more aggressive management strategies. PMID- 1940814 TI - Screening for asymptomatic bacteriuria in pregnancy: urinalysis vs urine culture. AB - BACKGROUND: Asymptomatic bacteriuria is common during pregnancy. Its average prevalence is 6%. It is an important risk factor for acute pyelonephritis, hypertension, preeclampsia, fetal wastage, low birthweight, and prematurity. This study was performed to determine the usefulness of urine microscopy as a substitute for doing a screening urine culture. METHODS: The medical records of all first trimester obstetric visits from 1984 to 1990 were reviewed at a major university. The results of 888 screening urinalyses were recorded and compared with those of subsequent urine cultures. RESULTS: Fifty-four cultures had growth of a single organism with a bacteria level of at least 1000 organisms per milliliter. In the prediction of a positive culture, the microscopic findings of five or more leukocytes per high-power field (HPF) showed a sensitivity of 94.4% and a specificity of 95.0%. CONCLUSION: Physicians should test the urine of all prenatal patients at their first visit and send to the laboratory only those specimens with 5 or more leukocytes per HPF. Using this method, unnecessary screening urine cultures will be substantially reduced. PMID- 1940815 TI - A comparison of albuterol and erythromycin for the treatment of acute bronchitis. AB - BACKGROUND: Based on observations that pulmonary function tests of patients with acute bronchitis resemble those of patients with asthma, it was hypothesized that a bronchodilator may be an effective form of treatment for patients with acute bronchitis. METHODS: Albuterol was compared with erythromycin in a prospective, randomized, double-blinded fashion. Participants were patients who presented to family physicians with a history of having a productive cough of less than 30 days' duration, no history or evidence of pneumonia, and no other pulmonary or cardiac disease. Patients completed a 7-day symptom diary and returned to their physician after 1 week of therapy for reexamination. RESULTS: Patients treated with albuterol were less likely to be coughing after 7 days of treatment than patients treated with erythromycin (41% vs 88%, P less than .05). This was true for both smokers and nonsmokers and in patients with purulent-appearing sputum. Trends toward an earlier improvement in cough and an improved feeling of well being also were observed in the albuterol group. No differences between groups were found as to the length of time before patients returned to work, the length of time until patients resumed normal activities, or the overall improvement in patient well-being. Minor side effects were equal in both groups. CONCLUSIONS: Oral albuterol may be more effective than commonly used antibiotics in relieving the symptoms of acute bronchitis. PMID- 1940816 TI - Lack of seasonal variability for recurrent otitis media in very young children. AB - BACKGROUND: Effective strategies are available to prevent recurrent otitis media (ROM). Because epidemiologic studies have demonstrated marked seasonal variation in acute otitis media (AOM), clinical guidelines often recommend cessation of prophylactic measures during the summer. Unfortunately, those studies did not separately assess seasonal variation in children with ROM, the group most likely to benefit from preventive measures. METHODS: The charts of 648 children who had at least one diagnosis of AOM were reviewed to count AOM rates by calendar month and age. Children with at least three infections in a 6-month period were assigned to a ROM group and analyzed separately. Seasonal variability was statistically assessed using the ranked-sums method of Hewitt. RESULTS: The criterion for ROM was met by 176 children (27%), who had 1096 episodes of AOM and accounted for 52% of all infections. In the ROM group, the monthly infection rate remained above 10% for the first 2 years of life. There was no seasonal variation in the ROM group under 1 year of age. The recurrence risk for those who met the ROM criterion was very high: first month, 32%; second month, 30%; third month, 22%; fourth month, 20%. CONCLUSIONS: The youngest otitis-prone children show a high rate of infection in the summer months and a very high rate of recurrence. In these children, decisions about beginning or continuing preventive measures should not be influenced by the season of the year. PMID- 1940817 TI - Influenza immunization: the impact of notifying patients of high-risk status. AB - BACKGROUND: The influenza immunization rate in the high-risk military and retired military population has not been reported. To determine this rate, and to test whether the rate could be improved by notifying patients of their high-risk status, a clinical trial was conducted using a postcard reminder as an intervention. METHODS: All 1068 high-risk patients enrolled in a large, residency affiliated, military family practice department were identified. Of these, 519 patients were randomly selected to receive a reminder postcard; the remainder (549) were not sent a card. The immunization rates of each group were compared. RESULTS: A significantly higher percentage of those to whom postcards were sent received an influenza immunization (25.2% vs 9.1%, P less than .001). This difference was significant in all demographic groups except in those less than 21 years of age and those 21 to 40 years of age, in which very few patients presented for immunization. In those in the study group aged 65 years and over, 46.7% were immunized vs 20% of controls (P less than .001). Those aged 65 years and older and those in the higher income group had higher immunization rates, while those aged 40 years and under had very low immunization rates. CONCLUSIONS: The influenza immunization rate among military beneficiaries in high-risk groups is low, but can be significantly improved with a reminder postcard. This intervention may be more effective in the older and higher-income segments of the high-risk population. The low immunization rates of the lower-income group and the younger age groups have significant public health implications and should be studied further. PMID- 1940818 TI - Caring for the terminally ill: resolving conflicting objectives between patient, physician, family, and institution. PMID- 1940819 TI - Herpetic whitlow: a case report. PMID- 1940820 TI - Shoulder dystocia caused by axillary cystic hygroma. PMID- 1940821 TI - Paying for prevention: recent developments and future strategies. PMID- 1940822 TI - Reduced calcium and inhibition of protein kinase C mimic the enhancement of ornithine decarboxylase activity of prolactin in Ambystoma tigrinum tissues. AB - We previously reported that prolactin (PRL) could increase the activity of ornithine decarboxylase (ODC) in liver slices taken from larval tiger salamanders (Ambystoma tigrinum). This action of the hormone was inhibited by oxytocin (OT), the calcium ionophore A23187, and diacyglycerol (DG) and was duplicated by 10 microM verapamil (VML), a calcium channel blocker. Here, we expand these results to show that 1) a higher dose of VML (50 microM) produces an additive effect with PRL; 2) addition of small amounts of calcium (0.1 mM) to the liver culture medium blocks PRL action; 3) neither nifedipine (NIF), a different type of calcium channel blocker, nor EDTA alter PRL action; and 4) gossypol, a reported inhibitor of protein kinase C, mimics PRL action. Additionally, we show that PRL increases ODC activity in tiger salamander tail skin in vitro, a tissue previously demonstrated to be a PRL target tissue in this species. The same set of treatments which we have shown to modify PRL effects on ODC in liver slices affects PRL action in the tail skin in a parallel manner. Thus, the mechanism whereby PRL enhances ODC activity appears to be the same in both these tissues. These results are discussed in conjunction with the findings from similar studies using mammalian tissues in an attempt to assess the current picture of the mechanism of PRL action and the possible role of inositol phospholipid turnover, calcium, and protein kinase C in the action of this hormone. PMID- 1940823 TI - The influence of denervation on grafted hindlimb regeneration of larval Xenopus laevis. AB - The aim of the present research is to ascertain whether in larval Xenopus laevis nerve-independence for the regeneration of early stage limbs and nerve-dependence of late stage limbs observed in a previous work (Filoni and Paglialunga, '90) is related to extrinsic (systemic) factors or to intrinsic changes taking place in the limb cells themselves during development. In this paper the regenerative capacity of early and late stage hindlimbs under the same extrinsic conditions, insofar as both are grafted onto the denervated hindlimbs of host larvae at the same developmental stage, is studied. All the grafted limbs are amputated after the host larvae have reached stage 57-58 (according to Nieuwkoop and Faber, '56). In experiment I, the grafted limb is amputated at stage 52, at the thigh level; in experiment II, the grafted limb is amputated at stage 54-55, at the tarsalia level; in experiment III the grafted limb is amputated at stage 57, at the tarsalia level. In all three experiments, together with the grafted limb, also the host limb is amputated at the tarsalia level. The results show that while grafted limbs amputated at stages 52 and 54-55 regenerate in the absence of nerves, grafted limbs amputated at stage 57 cannot. The failure of late stage grafted limbs to regenerate cannot be explained in terms of an immune-type inhibiting reaction since it has been observed also in denervated autografted limbs and in the host limbs. Since all the grafted limbs are in the same environmental conditions, the results show that in larval Xenopus laevis nerve independence for regeneration of early stage limbs and nerve-dependence of late stage limbs are not related to factors extrinsic to the limb but to intrinsic changes taking place in the limb cells themselves during development. PMID- 1940824 TI - Lens formation from the cornea following implantation into hindlimbs of larval Xenopus laevis: the influence of limb innervation and extent of differentiation. AB - Corneal fragments of larval Xenopus laevis at stage 48 (according to Nieuwkoop and Faber, '56), were implanted into sham denervated unamputated hindlimbs, denervated unamputated hindlimbs, amputated and sham denervated hindlimbs, and amputated and denervated hindlimbs of larvae at stages 52 and 57. The results show that unamputated limbs at stage 52, either innervated or denervated, manifest a weak capacity to promote the first lens-forming transformations of the outer cornea. This capacity is absent in both limb types at stage 57. After amputation, limbs of both early and late stages form a regenerative blastema and support lens formation from the outer cornea. Denervation of early stage limbs has no appreciable effect on blastema formation and lens-forming transformation of corneal implants. However, denervation of late stage limbs inhibits both processes. These results indicate that the limb tissues of the early stage limbs contain non-neural inductive factors at a low level and that after limb amputation and blastema formation the level of these factors becomes high enough to promote lens formation from implanted cornea, even after denervation. In contrast, the limb tissues of late stage limbs do not contain a suitable level of non-neural inductive factors. PMID- 1940825 TI - Growth and differentiation of the cultured secretory cells of the cow oviduct on reconstituted basement membrane. AB - Isolated bovine oviduct epithelial cells were cultured on plastic precoated with matrigel. The epithelial cells seeded on 10 mg/ml matrigel often organized themselves into hollow tubes or spheres with microvilli directed towards the lumen. This is the first report of describing the spontaneous tube formation of oviduct epithelial cells in vitro. The epithelial cells growing on this substratum became fully differentiated with the formation of junctional complexes and the production of secretory vesicles which migrated to apical plasmalemma. Epithelial cells seeded on 2 mg/ml matrigel (dry film) formed a subconfluent monolayer in 15-20 days after seeding. The histoarchitecture of the secretory cells growing on the matrigel dry film closely resembled that of intact epithelial cells. Occasional ciliated cells containing large numbers of mitochondria were observed in cell colonies growing on 2 mg/ml matrigel but they possessed very few intact cilia. The monolayer linearly incorporated 35S methionine into proteins up to 8 hr in presence of estradiol or progesterone. The fluorography of the newly synthesized proteins indicated that the cell extracts of estradiol-stimulated cells contained an additional protein of approximate molecular weight of 60 kd as compared to the extracts of cells incubated without steroids or incubated with progesterone. PMID- 1940826 TI - Initiation of placental lactogen-I production by blastocysts growing on a two dimensional surface and in hanging drops. AB - The mouse blastocyst undergoes a program of protein secretion during the perimplantation period including the initial production of placental lactogen-I (mPL-I) on day 6 of pregnancy. Although blastocysts collected on day 5 also produce mPL-I when cultured to form outgrowths on plastic dishes, it was not known if embryos have an intrinsic ability to produce mPL-I during culture in vitro, or if a specific uterine influence is necessary. Earlier experiments also suggested that attachment of the trophoblast to a stable surface may be a prerequisite for synthesis of mPL-I. Both questions were addressed by examining mPL-I production by day 3 and day 4 embryos cultured either on a two-dimensional tissue culture dish surface or in hanging drops. The presence of intracellular mPL-I was assayed by immunohistochemistry, while the secreted hormone was detected by its known position in two-dimensional electrophoresis gels. These experiments demonstrated that these earlier stage embryos do have an intrinsic program for mPL-I production which proceeds in vitro under various culture conditions. Synthesis of mPL-I occurred in embryos suspended in hanging drops as well as in those spreading on a solid two-dimensional surface, thus showing that adhesion to a surface is not required for production of this hormone. Although some mPL-I synthesis was seen in embryos cultured in medium containing BSA as the sole macromolecule, the inclusion of fibronectin either in dishes, where it supports attachment, or in the hanging drop system stimulated mPL-I secretion. Serum supplementation in both culture systems further increased growth and differentiation of the embryo, as well as mPL-I secretion, compared to fibronectin supplementation. PMID- 1940828 TI - Ethical issues in the forensic sciences. PMID- 1940827 TI - Peroxisomal beta-oxidation: insights from comparative biochemistry. AB - The activities of fatty acyl-CoA oxidase (FAO) and carnitine palmitoyl transferase (CPT), indices of the capacities of peroxisomal beta-oxidation and mitochondrial beta-oxidation, respectively, were determined in livers of several vertebrate species notable for differences in dietary fatty acid composition. In suckling rats FAO activities were half that in adult rats and CPT/FAO ratios twice that of adult rats. As their milk diet is dominated by medium chain fatty acids, this observation is consistent with current ideas about the role of peroxisomal beta-oxidation in rat liver in oxidation of long chain unsaturated fatty acids. In nectar-feeding hummingbirds (fatty acids synthesized de novo) FAO activities were 50% greater than adult rats and CPT/FAO ratios one-third less than adult rats, suggesting that peroxisomal beta-oxidation is relatively more important in this species, despite a fatty-acid-poor diet. In marine fish (herring, dogfish shark, hagfish) FAO activities were all less than 15% that of rats and undetectable in hagfish. CPT/FAO ratios were greater in herring (8.1) and hagfish (greater than 30) than adult rats (3.1), suggesting that peroxisomal beta-oxidation is relatively less important in these species despite a natural diet containing high levels of long chain polyunsaturated fatty acids. These data are discussed in relation to current ideas about the role of peroxisomes in beta oxidation of fatty acids. PMID- 1940829 TI - Policy options in forensic science--relevance to privatization. PMID- 1940830 TI - Managing change in a national forensic laboratory system. PMID- 1940831 TI - Privatization of forensic science laboratories--six years experience in South Australia. PMID- 1940832 TI - What made us ever think we could individualize using statistics? PMID- 1940833 TI - Forensic application of the polymerase chain reaction. PMID- 1940834 TI - Evaluation of DNA profiles: sense and nonsense. PMID- 1940835 TI - DNA analysis in human bone and other specimens of forensic interest: PCR typing and testing. PMID- 1940836 TI - Doping control of anabolic steroids. PMID- 1940837 TI - Addiction to what: will the real dopes please stand up. PMID- 1940838 TI - Doping in sport: old and new aspects of a worrying problem. PMID- 1940839 TI - The identification and analysis of Canadian designer drugs. PMID- 1940840 TI - Robotic automation of illicit heroin analyses. PMID- 1940841 TI - Steps towards automated forensic drug analysis. PMID- 1940842 TI - Mass poisoning in Perak, Malaysia or the Tale of the Nine Emperor Gods and rat tail noodles. PMID- 1940843 TI - Bits and pieces: investigation and analysis. PMID- 1940844 TI - Bits and pieces: serology, criminalistics, anthropology and odontology. PMID- 1940845 TI - Proceedings of the 12th meeting of the International Association of Forensic Sciences, Adelaide, 24-29 October 1990. PMID- 1940846 TI - Single channel studies of the phosphorylation of K+ channels in the squid giant axon. I. Steady-state conditions. AB - Phosphorylation of the delayed rectifier channel of squid potentiates the macroscopic K+ current and slows its activation kinetics. We have studied this phenomenon at the single channel level using the cut-open axon technique under steady-state conditions. In 10 mM external K+/310 mM internal K+ there are predominantly two types of channels present, a 20-pS and a 40-pS channel. In steady state at depolarized potentials, the 40-pS channel was most active, whereas the 20-pS channel tended to disappear due to a slow inactivation process. Two methods were developed to shift the population of channels toward a dephosphorylated state. One method consisted of predialyzing a whole axon with solutions containing no ATP, while recording the currents under axial-wire voltage clamp. A piece of axon was then removed and cut open, and single channel currents were recorded from the cut-open axon. A second method was based on the difference in diffusion coefficients for ATP and proteins such as the endogenous phosphatase. The axon was cut open in a solution that did not contain Ca2+ or Cl- in order to maintain the axoplasm structurally intact and permit endogenous phosphatase to act on the membrane while ATP diffused away, before removing the axoplasm and forming a membrane patch. When dephosphorylating conditions were used, the steady-state open probability of the 40-pS channel at 42 mV was very low (less than 0.0002), and the channel openings appeared as a series of infrequent, short-duration events. The channel activity was increased up to 150 fold by photoreleasing caged ATP inside the patch pipette in the presence of the catalytic subunit of protein kinase A. The sharp increase in open probability could be accounted for by a decrease of the slow component of the closed time distribution from 23 s to 170 ms with little change in the distribution of open times (1-2 ms) and no change in the single channel current amplitude. In voltage jump experiments the contribution of the 40-pS channel to the delayed rectifier current was often small due to the large values of the latency to the first opening. PMID- 1940847 TI - Competitive Mg2+ block of a large-conductance, Ca(2+)-activated K+ channel in rat skeletal muscle. Ca2+, Sr2+, and Ni2+ also block. AB - The patch-clamp technique was used to investigate the effect of intracellular Mg2+ (Mgi2+) on the conductance of the large-conductance, Ca(2+)-activated K+ channel in cultured rat skeletal muscle. Measurements of single-channel current amplitudes indicated that Mgi2+ decreased the K+ currents in a concentration dependent manner. Increasing Mgi2+ from 0 to 5, 10, 20, and 50 mM decreased channel currents by 34%, 44%, 56%, and 73%, respectively, at +50 mV. The magnitude of the Mgi2+ block increased with depolarization. For membrane potentials of -50, +50, and +90 mV, 20 mM Mgi2+ reduced the currents 22%, 56%, and 70%, respectively. Mgi2+ did not change the reversal potential, indicating that Mg2+ does not permeate the channel. The magnitude of the Mgi2+ block decreased as the concentration of K+ was increased. At a membrane potential of +50 mv, 20 mM Mgi2+ reduced the currents 71%, 56%, and 25% for Ki+ of 75, 150, and 500 mM. These effects of Mgi2+, voltage, and K+ were totally reversible. Although the Woodhull blocking model could approximate the voltage and concentration effects of the Mgi2+ block (Kd approximately 30 mM with 150 mM symmetrical K+; electrical distance approximately 0.22 from the inner surface), the Woodhull model could not account for the effects of K+. Double reciprocal plots of 1/single channel current vs. 1/[K+] in the presence and absence of Mgi2+, indicated that the Mgi2+ block is consistent with apparent competitive inhibition between Mgi2+ and Ki+. Cai2+, Nii2+, and Sri2+ were found to have concentration- and voltage-dependent blocking effects similar, but not identical, to those of Mgi2+. These observations suggest the blocking by Mgi2+ of the large conductance, Ca(2+)-activated K+ channel is mainly nonspecific, competitive with K+, and at least partially electrostatic in nature. PMID- 1940848 TI - Single channel studies of the phosphorylation of K+ channels in the squid giant axon. II. Nonstationary conditions. AB - The effects of phosphorylation on the properties of the 20-pS channel of the squid giant axon were studied using the cut-open axon technique. Phosphorylation of the channel was achieved by photoreleasing caged ATP (inside the patch pipette) in the presence of the catalytic subunit of the protein kinase A. An inverted K+ gradient (500 K+ external parallel 5 K+ internal) was used to study the activation process. Phosphorylation decreased the frequency of openings of the channel at most potentials by shifting the probability vs. voltage curve toward more positive potentials. The mean open times showed no voltage dependence and were not affected by phosphorylation. The distribution of first latencies, on the other hand, displayed a sharp voltage dependence. Phosphorylation increased the latency to the first opening at all potentials, shifting the median first latency vs. voltage curve toward more positive potentials. The slow inactivation process was studied in the presence of a physiological K+ gradient (10 K+ external parallel 310 K+ internal). Pulses to 40 mV from different holding potentials were analyzed. Phosphorylation increases the overall ensemble probability by decreasing the number of blank traces. A single channel inactivation curve was constructed by computing the relative appearance of blank traces at different holding potentials before and after photoreleasing caged ATP. As determined in dialyzed axons, the effect of phosphorylation consisted in a shift of the inactivation curve toward more positive potentials. The 20-pS channel has the same characteristics as the delayed rectifier current in activation kinetics, steady-state inactivation, and phosphorylation effects. PMID- 1940849 TI - Dual effect of adenosine triphosphate on the apical small conductance K+ channel of the rat cortical collecting duct. AB - We used the patch-clamp technique to study the effects of ATP on the small conductance potassium channel in the apical membrane of rat cortical collecting duct (CCD). This channel has a high open probability (0.96) in the cell-attached mode but activity frequently disappeared progressively within 1-10 min after channel excision (channel "run-down"). Two effects of ATP were observed. Using inside-out patches, low concentrations of ATP (0.05-0.1 mM) restored channel activity in the presence of cAMP-dependent protein kinase A (PKA). In contrast, high concentrations (1 mM) of adenosine triphosphate (ATP) reduced the open probability (Po) of the channel in inside-out patches from 0.96 to 0. 1.2 mM adenosine diphosphate (ADP) also blocked channel activity completely, but 2 mM adenosine 5'-[beta,gamma-imido]triphosphate (AMP-PNP), a nonhydrolyzable ATP analogue, reduced Po only from 0.96 to 0.87. The half-maximal inhibition (Ki) of ATP and ADP was 0.5 and 0.6 mM, respectively, and the Hill coefficient of both ATP and ADP was close to 3. Addition of 0.2 or 0.4 mM ADP shifted the Ki of ATP to 1.0 and 2.0 mM, respectively. ADP did not alter the Hill coefficient. Reduction of the bath pH from 7.4 to 7.2 reduced the Ki of ATP to 0.3 mM. In contrast, a decrease of the free Mg2+ concentration from 1.6 mM to 20 microM increased the Ki of ATP to 1.6 mM without changing the Hill coefficient; ADP was still able to relieve the ATP-induced inhibition of channel activity over this low range of free Mg2+ concentrations. The blocking effect of ATP on channel activity in inside-out patches could be attenuated by adding exogenous PKA catalytic subunit to the bath. The dual effects of ATP on the potassium channel can be explained by assuming that (a) ATP is a substrate for PKA that phosphorylates the potassium channel to maintain normal function. (b) High concentrations of ATP inhibit the channel activity; we propose that the ATP induced blockade results from inhibition of PKA-induced channel phosphorylation. PMID- 1940850 TI - Kinetics of a Ca(2+)-sensitive cross-bridge state transition in skeletal muscle fibers. Effects due to variations in thin filament activation by extraction of troponin C. AB - The rate constant of tension redevelopment (ktr; 1986. Proc. Natl. Acad. Sci. USA. 83:3542-3546) was determined at various levels of thin filament activation in skinned single fibers from mammalian fast twitch muscles. Activation was altered by (a) varying the concentration of free Ca2+ in the activating solution, or (b) extracting various amounts of troponin C (TnC) from whole troponin complexes while keeping the concentration of Ca2+ constant. TnC was extracted by bathing the fiber in a solution containing 5 mM EDTA, 10 mM HEPES, and 0.5 mM trifluoperazine dihydrochloride. Partial extraction of TnC resulted in a decrease in the Ca2+ sensitivity of isometric tension, presumably due to disruption of near-neighbor molecular cooperativity between functional groups (i.e., seven actin monomers plus associated troponin and tropomyosin) within the thin filament. Altering the level of thin filament activation by partial extraction of TnC while keeping Ca2+ concentration constant tested whether the Ca2+ sensitivity of ktr results from a direct effect of Ca2+ on cross-bridge state transitions or, alternatively, an indirect effect of Ca2+ on these transitions due to varying extents of thin filament activation. Results showed that the ktr-pCa relation was unaffected by partial extraction of TnC, while steady-state isometric tension exhibited the expected reduction in Ca2+ sensitivity. This finding provides evidence for a direct effect of Ca2+ on an apparent rate constant that limits the formation of force-bearing cross-bridge states in muscle fibers. Further, the kinetics of this transition are unaffected by disruption of near-neighbor thin filament cooperativity subsequent to extraction of TnC. Finally, the results support the idea that the steepness of the steady-state isometric tension-calcium relationship is at least in part due to mechanisms involving molecular cooperativity among thin filament regulatory proteins. PMID- 1940851 TI - Separation of intramembrane charging components in low-calcium solutions in frog skeletal muscle. AB - The inactivation of charge movement components by small (-100 to -70 mV) shifts in holding potential was examined in voltage-clamped intact amphibian muscle fibers in low [Ca2+], Mg(2+)-containing solutions. The pulse protocols used both large voltage excursions and smaller potential steps that elicited prolonged (q gamma) transients. Charge species were distinguished through the pharmacological effects of tetracaine. These procedures confirmed earlier observations in cut fibers and identified the following new properties of the q gamma charge. First, q gamma, previously defined as the tetracaine-sensitive charge, is also the component primarily responsible for the voltage-dependent inactivation induced by conditions of low extracellular [Ca2+]. Second, this inactivation separates a transient that includes a "hump" component and which has kinetics and a voltage dependence distinct from the monotonic decay that remains. Third, q gamma, previously associated with delayed charge movements, can also contribute significant charge transfer at early times. These findings suggest that the parallel inhibition of calcium signals and charge movements reported in low [Ca2+] solutions arises from influences on q gamma charge (Brum et al., 1988a, b). They also reconcile reports that implicate tetracaine-sensitive (q gamma) charge in excitation-contraction coupling with evidence that early intramembrane events are also involved in this process (Pizarro et al., 1989). Finally, they are relevant to hypotheses of possible feedback or feed-forward roles of q gamma in excitation-contraction coupling. PMID- 1940852 TI - Comparison of charge movement components in intact and cut twitch fibers of the frog. Effects of stretch and temperature. AB - Charge movements were measured in frog intact fibers with the three microelectrode technique and in cut fibers with the double Vaseline gap technique. At 13-14 degrees C, the ON segments of charge movement records from both preparations showed an early I beta component and a late I gamma hump component. When an intact fiber was cooled to 4-7 degrees C, the time-to-peak of I gamma (tp,gamma) was prolonged, but I gamma still appeared as a hump. Q-V plots from intact fibers at 4-7 degrees C were fitted with a sum of two Boltzmann distribution functions (method 1). The more steeply voltage-dependent component, identified with Q gamma, accounted for 32.1% (SEM 2.2%) of the total charge. This fraction was larger than the 22.6% (SEM 1.5%) obtained by separating the ON currents with a sum of two kinetic functions (method 2). The total charge in cut fibers stretched to a sarcomere length of 3.5 microns at 13-14 degrees C was separated into Q beta and Q gamma by methods 1 and 2. The fraction of Q gamma in the total charge was 51.3% (SEM 1.7%) and 53.7% (SEM 1.8%), respectively, suggesting that cut fibers have a larger proportion of Q gamma:Q beta than intact fibers. When cut fibers were stretched to a sarcomere length of 4 microns, the proportion of Q gamma:Q beta was unchanged. Between 4 and 13 degrees C, the Q10 of l/tp,gamma in intact fibers was 2.33 (SEM 0.33) and that of 1/tau beta was less than 1.44 (SEM 0.04), implying that the kinetics of I gamma has a steeper temperature dependence than the kinetics of I beta. When cut fibers were cooled from 14 to 6 degrees C, I gamma in the ON segment generally became too broad to be manifested as a hump. In a cut fiber in which I gamma was manifested as a hump, the Q10 of l/tp,gamma was 2.08 and that of l/tau beta was less than 1.47. Separating the Q-V plots from cut fibers at different temperatures by method 1 showed that the proportion of Q gamma:Q beta was unaffected by temperature change. The appearance of I gamma humps at low temperatures in intact fibers but generally not in cut fibers suggests an intrinsic difference between the two fiber preparations. PMID- 1940853 TI - Kinetic properties of intramembrane charge movement under depolarized conditions in frog skeletal muscle fibers. AB - Intramembrane charge movement was measured on skeletal muscle fibers of the frog in a single Vaseline-gap voltage clamp. Charge movements determined both under polarized conditions (holding potential, VH = -100 mV; Qmax = 30.4 +/- 4.7 nC/micro(F), V = -44.4 mV, k = 14.1 mV; charge 1) and in depolarized states (VH = 0 mV; Qmax = 50.0 +/- 6.7 nC/micro(F), V = -109.1 mV, k = 26.6 mV; charge 2) had properties as reported earlier. Linear capacitance (LC) of the polarized fibers was increased by 8.8 +/- 4.0% compared with that of the depolarized fibers. Using control pulses measured under depolarized conditions to calculate charge 1, a minor change in the voltage dependence (to V = -44.6 mV and k = 14.5 mV) and a small increase in the maximal charge (to Qmax = 31.4 +/- 5.5 nC/micro(F] were observed. While in most cases charge 1 transients seemed to decay with a single exponential time course, charge 2 currents showed a characteristic biexponential behavior at membrane potentials between -90 and -180 mV. The voltage dependence of the rate constant of the slower component was fitted with a simple constant field diffusion model (alpha m = 28.7 s-1, V = -124.0 mV, and k = 15.6 mV). The midpoint voltage (V) was similar to that obtained from the Q-V fit of charge 2, while the steepness factor (k) resembled that of charge 1. This slow component could also be isolated using a stepped OFF protocol; that is, by hyperpolarizing the membrane to -190 mV for 200 ms and then coming back to 0 mV in two steps. The faster component was identified as an ionic current insensitive to 20 mM Co2+ but blocked by large hyperpolarizing pulses. These findings are consistent with the model implying that charge 1 and the slower component of charge 2 interconvert when the holding potential is changed. They also explain the difference previously found when comparing the steepness factors of the voltage dependence of charge 1 and charge 2. PMID- 1940854 TI - Solvent drag measurement of transcellular and basolateral membrane NaCl reflection coefficient in kidney proximal tubule. AB - The NaCl reflection coefficient in proximal tubule has important implications for the mechanisms of near isosmotic volume reabsorption. A new fluorescence method was developed and applied to measure the transepithelial (sigma NaClTE) and basolateral membrane (sigma NaClcl) NaCl reflection coefficients in the isolated proximal straight tubule from rabbit kidney. For sigma NaClTE measurement, tubules were perfused with buffers containing 0 Cl, the Cl-sensitive fluorescent indicator 6-methoxy-N-[3-sulfopropyl] quinolinium and a Cl-insensitive indicator fluorescein sulfonate, and bathed in buffers of differing cryoscopic osmolalities containing NaCl. The transepithelial Cl gradient along the length of the tubule was measured in the steady state by a quantitative ratio imaging technique. A mathematical model based on the Kedem-Katchalsky equations was developed to calculate the axial profile of [Cl] from tubule geometry, lumen flow, water (Pf) and NaCl (PNaCl) permeabilities, and sigma NaClTE. A fit of experimental results to the model gave PNaCl = (2.25 +/- 0.2) x 10(-5) cm/s and sigma NaClTE = 0.98 +/ 0.03 at 23 degrees C. For measurement of sigma NaClbl, tubule cells were loaded with SPQ in the absence of Cl. NaCl solvent drag was measured from the time course of NaCl influx in response to rapid (less than 1 s) Cl addition to the bath solution. With bath-to-cell cryoscopic osmotic gradients of 0, -60, and +30 mosmol, initial Cl influx was 1.23, 1.10, and 1.25 mM/s; a fit to a mathematical model gave sigma NaClbl = 0.97 +/- 0.04. These results indicate absence of NaCl solvent drag in rabbit proximal tubule. The implications of these findings for water and NaCl movement in proximal tubule are evaluated. PMID- 1940855 TI - Low molecular weight mRNA encodes a protein that controls serotonin 5-HT1c and acetylcholine M1 receptor sensitivity in Xenopus oocytes. AB - Serotonin 5-HT1c and acetylcholine M1 receptors activate phosphoinositidase, resulting in an increased formation of IP3 and 1,2 diacylglycerol. In Xenopus oocytes injected with mRNA encoding either of these receptors, Ca2+ released from intracellular stores in response to IP3 then opens Ca(2+)-gated Cl-channels. In the present experiments, oocytes expressing a transcript from a cloned mouse serotonin 5-HT1c receptor were exposed to identical 15-s pulses of agonist, administered 2 min apart; the second current response was two to three times that of the first. However, in those oocytes coinjected with the 5-HT1c receptor transcript and a low molecular weight fraction (0.3-1.5 kb) of rat brain mRNA, the second current response was approximately 50% of the first. Thus, the low molecular weight RNA encodes a protein (or proteins) that causes desensitization. Experiments using fura-2 or a Ca(2+)-free superfusate indicated that desensitization of the 5-HT1c receptor response does not result from a sustained elevation of intracellular Ca2+ level or require the entry of extracellular Ca2+. Photolysis of caged IP3 demonstrated that an increase in IP3 and a subsequent rise in Ca2+ do not produce desensitization of either the IP3 or 5-HT1c peak current responses. Furthermore, in oocytes coinjected with the low molecular weight RNA and a transcript from the rat M1 acetylcholine receptor, the M1 current response was greatly attenuated. Our data suggest that the proteins involved in attenuation of the M1 current response and desensitization of the 5 HT1c current response may be the same. PMID- 1940856 TI - Acquisition of tomato yellow leaf curl virus by the whitefly Bemisia tabaci. AB - Tomato yellow leaf curl virus (TYLCV) genomic DNA can be detected by Southern blot analysis in nucleic acid extracted from a single whitefly. Acquisition of TYLCV by individual whiteflies in relation to the length of the access period, the virus concentration in, and the developmental stage of plant tissues was studied. The frequency of TYLCV detection increased with the length of the access period; DNA was detected in 15% of whiteflies tested after a period of access to infected tissue of 30 min, regardless of whether it had a high or a low virus content (5 ng or 0.05 ng TYLCV DNA/micrograms plant chromosomal DNA), and in all insects tested after an 8 h period of access to all the plants. Those insects which had access to the youngest leaves of source plants, which have a high virus content, acquired detectable TYLCV DNA within 2 h. Insects which had access to a tissue for the same period acquired variable amounts of TYLCV DNA; insects feeding on plants with a low virus concentration acquired amounts of viral DNA comparable to those acquired by insects feeding on plants containing a 100-fold greater concentration of virus. Viruliferous insects retained TYLCV DNA for at least 13 days when placed on uninfected tomato plants. In these tests, whitefly could not acquire more than 600 million virus genomes (1 ng viral DNA), suggesting the existence of factors controlling the number of virions present in an insect. PMID- 1940857 TI - Tubular structures involved in movement of cowpea mosaic virus are also formed in infected cowpea protoplasts. AB - In cowpea plant cells infected with cowpea mosaic virus, tubular structures containing virus particles are formed in the plasmodesmata between adjacent cells; these structures are supposedly involved in cell-to-cell spread of the virus. Here we show that similar tubular structures are also formed in cowpea protoplasts, from which the cell wall and plasmodesmata are absent. Between 12 and 21 h post-inoculation, tubule formation starts in the periphery of the protoplast at the level of the plasma membrane. Upon assembly, the virus containing tubule is enveloped by the plasma membrane and extends into the culture medium. This suggests that the tubule has functional polarity and makes it likely that a tubule 'grows' into a neighbouring cell in vivo. On average, 75% of infected protoplasts were shown to possess tubular structures extending from their surface. The tubule wall was 3 to 4 nm thick and they were up to 20 microns in length, as shown by fluorescent light microscopy and negative staining electron microscopy. By analogy to infected plant cells, both the viral 58K/48K movement and capsid proteins were located in these tubules, as determined by immunofluorescent staining and immunogold labelling using specific antisera against these proteins. These results demonstrate that the formation of tubules is not necessarily dependent on the presence of plasmodesmata or the cell wall, and that they are composed, at least in part, of virus-encoded components. PMID- 1940858 TI - The complete nucleotide sequence of pea seed-borne mosaic virus RNA. AB - The complete nucleotide sequence of the RNA genome of pea seed-borne mosaic virus (PSbMV) was determined from cloned cDNA and by direct sequencing of viral RNA. The PSbMV genomic sequence was determined to be 9924 nucleotides in length excluding the poly(A) tract. The RNA contained an open reading frame (ORF) of 9618 nucleotides with the potential to encode a polyprotein with a calculated Mr of 364000 (364K). The ORF was flanked by a 5' untranslated leader sequence of 143 nucleotides and a 3' untranslated region of 163 nucleotides. A comparison of the PSbMV polyprotein with the polyproteins of the potyviruses tobacco etch virus (TEV), tobacco vein mottling virus (TVMV), plum pox virus (PPV) and potato virus Y (PVY) showed that PSbMV had a similar genome organization. The polyproteins had a high level of amino acid identity except in the N-terminal region, which varied in both sequence and length. Putative proteolytic cleavage sites were identified in the polyprotein of PSbMV by comparison with those identified for other potyviruses. The cleavage site between the 6K protein and the 49K proteinase is proposed to occur at the C-terminal side of glutamic acid and not at the C terminal side of glutamine as in other potyviruses. In addition to the five proteolytic cleavage sites for the 49K proteinase identified previously, a sixth putative cleavage site was identified internally in the 49K proteinase of PSbMV, as well as in the 49K proteinases of TEV, TVMV, PPV, PVY and soybean mosaic virus. Cleavage at this site in the 49K proteinases of TEV, TVMV and PPV would result in an N-terminal protein of 22K to 24K, which is similar in size to the size determined for their VPgs. PMID- 1940859 TI - The location of the 5' end of the potato leafroll luteovirus subgenomic coat protein mRNA. AB - Northern blot analysis of nucleic acid from potato plant tissues and tobacco protoplasts infected with a Scottish isolate of potato leafroll luteovirus (PLRV) detected the 6 kb genomic RNA and one subgenomic RNA species of about 2.7 kb; RNA extracted from virus particles contained only the genomic species. Blotting with small defined probes suggested that the location of the 5' end of the subgenomic RNA was between 2380 and 2510 nucleotides from the 3' end of the PLRV genome (between 3370 and 3500 nucleotides from the 5' end of PLRV Dutch isolate RNA). When RNA extracted from PLRV-infected or mock-inoculated protoplasts was used as the template for primer extension using primers complementary to the sequence at, or upstream of, the initiation codon of the coat protein gene, a single major infection-specific product was detected. A primer complementary to the sequence between 162 and 179 nucleotides upstream of the coat protein AUG yielded a product of 56 nucleotides. Thus, the subgenomic RNA has a leader sequence of 212 nucleotides, is 2505 nucleotides in length and starts at a position equivalent to 3376 nucleotides from the 5' end of the PLRV-Dutch genome, 11 nucleotides upstream of the termination codon of the putative polymerase gene. The nucleotide sequence immediately downstream of this position closely resembles that of the 5' end of the PLRV genomic RNA. PMID- 1940860 TI - Infectious in vitro RNA transcripts derived from cloned cDNA of the cucurbit potyvirus, zucchini yellow mosaic virus. AB - A full-length cDNA clone of the RNA genome of the cucurbit potyvirus zucchini yellow mosaic virus (ZYMV) was constructed downstream from a bacteriophage T7 RNA polymerase promoter. A single extra guanosine residue not present in ZYMV RNA was added to the 5' and 3' ends. Capped (m7GpppG) ZYMV RNA transcripts were infectious in 10 of 91 Cucurbita pepo test plants; uncapped RNA transcripts were not infectious. The appearance of symptoms in plants inoculated with the infectious transcript was delayed for more than a week compared to plants inoculated with native viral RNA. The progeny virions recovered from infected plants had the same biological properties (aphid non-transmissibility and typical symptoms) as the parental virus. The progeny virions also reacted positively with ZYMV antiserum and ZYMV-specific probes by dot blot hybridization. The authenticity of the progeny virus was verified by identifying a specific molecular marker (C substituted for T in the 3' non-coding region) using nucleotide sequence analysis. PMID- 1940862 TI - Selection kinetics during serial cell culture passage of mixtures of wild-type Autographa californica nuclear polyhedrosis virus and its recombinant Ac360-beta gal. AB - Detailed analysis of the selection process in serial co-infections of cell cultures by wild-type Autographa californica nuclear polyhedrosis virus (AcNPV) strain E2 (AcNPV/E2) and Ac360-beta-gal, a genetically engineered strain, shows that the unaltered strain was clearly dominant even when it initially constituted the minority component in the inoculum. A method of calculating a selection coefficient that quantifies the relative advantage of one strain of virus over the other under specific culture conditions is described. Calculated selection coefficients were relatively homogeneous and almost exclusively favoured the progenitor. Selection pressure was not influenced by the relative proportions of the two strains in the population. Selection coefficients, as determined in the present study, may be useful for evaluating the effect of a genetic alteration on viral fitness under specified conditions. Unexpected high frequencies of mixed phenotype plaques were observed during infectivity titrations of media from early serial passages of co-infected cultures. Statistical evaluation implicates some non-heritable combinational phenomenon. Virus plated from mixed phenotype plaques show high segregation of phenotypes implying that genetic recombination does not contribute in a major way to the high mixed phenotype frequencies. Electron microscopic examination of virion pellets from infected 72 h cell culture media similarly argue against co-envelopment as a major contributory factor to the high frequency of mixed phenotype plaques. The cause remains undetermined. PMID- 1940861 TI - Location and nucleotide sequence of the gene encoding the viral enhancing factor of the Trichoplusia ni granulosis virus. AB - The gene encoding the viral enhancing factor (VEF) of Trichoplusia ni granulosis virus has been cloned from a lambda gt11 expression library, and the complete nucleotide sequence determined. The VEF gene encodes a protein with a predicted Mr of 104K which does not share homology with any previously reported proteins. A possible promoter is located four nucleotides upstream of the initiation codon and represents a consensus baculovirus late promoter (ATAAG). This has been confirmed by the identification of VEF mRNA in Northern blots of infected larvae 6 days but not 3 days post-infection. Using an anti-VEF-TrpE polyclonal antiserum in Western blots of dissolved viral occlusion bodies, related proteins have been identified in both Pseudaletia unipuncta granulosis virus Hawaiian strain (PuGV H) and Heliothis armigera GV (HaGV), but not in Erinnyis ello GV (EeGV), T. ni singly enveloped nuclear polyhedrosis virus (TnSNPV) or Autographa californica multiply enveloped NPV (AcMNPV). Similar results were obtained with Southern blots of genomic digests. DNA fragments homologous to an internal portion of the VEF gene were found in PuGV-H and HaGV but not in EeGV, TnSNPV or AcMNPV. PMID- 1940863 TI - Involvement of the influenza A virus PB2 protein in the regulation of viral gene expression. AB - To determine the function(s) of the PB2 protein of influenza A virus, six temperature-sensitive (ts) mutants of A/Udorn/72 (H3N2) virus, each carrying a ts mutation in the PB2 gene, were analysed for virus RNA and protein synthesis. One of the mutants, ICRC27, exhibited unique phenotypes and was characterized in detail. At the non-permissive temperature, 40 degrees C, the accumulation of mRNA for each genome segment was reduced severely, leading to delayed and reduced synthesis of viral proteins, complementary and viral RNAs (cRNAs and vRNAs). At the permissive temperature, 34 degrees C, the mutant virus produced several-fold greater concentrations of both mRNAs and cRNAs of PB2, PB1 and PA segments than wild-type virus. The synthesis of the three polymerase proteins and the induction of RNA polymerase activity were also greatly increased. By contrast, the expression of the haemagglutinin (HA) gene was severely suppressed. The over production of the polymerase mRNAs was not observed during primary transcription, i.e. in the presence of cycloheximide. The ts+ revertants of ICRC27 did not exhibit the ts defects and also lost most of the non-ts phenotypes at 34 degrees C. These observations indicate that the PB2 protein participates not only in the synthesis of viral RNAs, but also in the regulation of viral gene expression, i.e. in the down-regulation of the three polymerase genes and the up-regulation of the HA gene during secondary transcription. PMID- 1940864 TI - Sequence analysis of the haemagglutinin (HA) of influenza A (H1N1) viruses present in clinical material and comparison with the HA of laboratory-derived virus. AB - We used the polymerase chain reaction to amplify the HA1 coding region of influenza A (H1N1) viruses present in clinical material from recent cases of influenza in the U.K. Previously, we have demonstrated that isolation of human influenza viruses in embryonated hens' eggs selects variants which have amino acid substitutions in their haemagglutinin (HA) clustering around the receptor binding site. Such egg-selected variants are often antigenically distinct from each other and from corresponding viruses isolated on mammalian cells. Since in general the virus used for vaccine production is an egg-adapted virus, it is important to determine the extent to which these variants are present in the natural virus which causes disease in man. To achieve this, amplified products from clinical material were cloned and many individual clones sequenced. Our results indicate that the HA of the naturally occurring virus is relatively homogeneous and represented by virus isolated in the laboratory on MDCK cells, whereas the variants isolated in eggs are present only at low levels in clinical material. PMID- 1940865 TI - Glycosylation of measles virus haemagglutinin protein in infected cells. AB - Processing of the measles virus haemagglutinin (H) protein was analysed by the pulse-chase method, immunoprecipitation with an anti-H monoclonal antibody and SDS-polyacrylamide gel electrophoresis, combined with the addition of carbonyl cyanide m-chlorophenylhydrazone (CCCP) or monensin (inhibitors of intracellular processing of secretory proteins) to cultures and digestion of the protein with endoglycosidase H or neuraminidase. The apparent Mr of the H protein was increased from 74K to 78K during the chase period. Addition of either CCCP or monensin to the chase medium inhibited the appearance of the 78K H protein, but not the immunoreactivity of the H protein or dimer formation, suggesting that these two events occur in the rough endoplasmic reticulum. The 74K H protein processed in the presence of CCCP was fully sensitive to endoglycosidase H digestion, whereas the 74K H protein processed in the presence of monensin was partially resistant to endoglycosidase H. In experiments using 3H-labelled sugars, [3H]galactose was incorporated into the 74K H protein in the presence of monensin. Neuraminidase treatment increased the electrophoretic mobility of the 78K H protein to 74K. Only the 78K H protein was detected on the surface of untreated cells, and it was resistant to endoglycosidase H digestion. These data suggest that after galactose addition sialic acid is added to the H protein in the trans-Golgi complex and then the mature 78K H protein is transported to the cell surface. PMID- 1940867 TI - In vitro homotypic and heterotypic interference by defective interfering particles of West Nile virus. AB - Defective interfering (DI) particles of the flavivirus West Nile (WN) were generated after as few as two high multiplicity serial passages in Vero and LLC MK2 cells. Six cell lines (Vero, LLC-MK2, L929, HeLa, BHK-21 and SW13) were used to assay interference by DI particles in a yield reduction assay. Interference was found to vary depending on the cell type used. The highest levels of interference were obtained in LLC-MK2 cells, whereas no detectable effect was observed in BHK-21 and SW13 cells. The ability of DI virus to be propagated varied depending on the cell line used; no detectable propagation of DI virus was observed in SW13 cells. Optimum interference was obtained following co-infection of cells with DI virus and standard virus at a multiplicity of 5. Interference between DI and standard viruses occurred only when they were co-infected or when cells were infected with DI virus 1 h before standard virus. Investigation of heterotypic interference by DI particles of WN virus strains from Sarawak, India and Egypt revealed that interference was dependent on the strain of WN virus or flavivirus used as standard virus. A measure of the similarity between five strains of WN virus and other flaviviruses was made on the basis of interference by DI viruses, and was found to be similar to that based on haemagglutination inhibition tests using a panel of monoclonal antibodies. PMID- 1940866 TI - Enhancement of human immunodeficiency virus type 1 infection by cationic liposomes: the role of CD4, serum and liposome-cell interactions. AB - We have reported previously the enhancement of the infectivity of human immunodeficiency virus type 1 (HIV-1) by liposomes composed of the cationic lipid N-[2,3-(dioleyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTMA). To determine the mechanism by which this process occurs, we have investigated the role of CD4, serum concentration and liposome-cell interactions in the DOTMA mediated stimulation of HIV-1 infection of A3.01 cells. Serum alone significantly inhibited the binding and infectivity of HIV-1, but DOTMA-mediated enhancement of infectivity was more pronounced in the presence of serum than in its absence. HIV 1 binding to cells was increased in the presence of DOTMA liposomes, DEAE-dextran and polybrene, all of which also enhanced infectivity to a similar extent at comparable concentrations. Fluorescence dequenching measurements indicated that DOTMA liposomes fused with HIV-1, but not with cell membranes, in the presence of serum. The enhancing effect of DOTMA liposomes on HIV-1 infectivity was CD4 dependent, and appeared to involve virus-liposome fusion and liposome binding to the cell surface. DOTMA liposomes did not mediate infection of the CD4-K562 and Raji cell lines. PMID- 1940868 TI - Intragenic and intergenic recombination between temperature-sensitive mutants of vaccinia virus. AB - The frequency of recombination for a complete set of two-factor crosses between vaccinia virus mutations separated by distances of between 54 and 10692 bp was determined. The results show that in intragenic crosses there is a linear relationship between the recombination frequency observed and distances between the mutations of up to 700 bp. However, no length dependence of the recombination frequency in intergenic crosses with a distance between mutations of 328 to greater than 10000 bp is observed. We attribute this lack of dependence to the high rate of viral DNA interchange, which makes some step other than the cross over event rate-limiting. Furthermore, we believe that the observed difference in recombination frequency between inter- and intragenic recombination is due to complementation between temperature-sensitive mutants at the permissive temperature. PMID- 1940869 TI - Prostaglandin A inhibits replication of human immunodeficiency virus during acute infection. AB - An antiviral effect of prostaglandins (PGs) of the A series on the replication of human immunodeficiency virus (HIV) has been determined. In the T cell line C8166 under single growth cycle conditions, PGA1 reduced the number of infectious progeny 1000-fold in the absence of cytotoxicity. Thus, inhibition of HIV replication by PGA1 represents a true antiviral phenomenon. The number and size of virus-induced syncytia, and the amount of viral antigen were also drastically reduced. The effect was specific for PGAs because PGA2 was also inhibitory, whereas PGB1, PGE1 and PGE2 were inactive. Virus adsorption and penetration do not appear to be targets of antiviral action because PGA1 substantially reduced virus replication, even when added 5 h post-infection. PGA1 did not inhibit viral reverse transcriptase, as determined by in vitro assays, suggesting that its antiviral action is not the consequence of a direct inhibitory effect on this enzyme. PGA1 also inhibited the replication of HIV-1 in CEM x 174 cells, but with less potency. Previously, intravenous infusion of PGA1 into human volunteers has shown no significant deleterious side-effects and thus these observations suggest that PGAs might have potential as antiviral agents in humans. PMID- 1940870 TI - Monoclonal antibodies differentiate between the haemagglutinating and the receptor-destroying activities of bovine coronavirus. AB - A relatively simple and sensitive method is described which enables the effect of monoclonal antibodies (MAbs) on the receptor-destroying enzyme (RDE) and the haemagglutination (HA) activity of bovine coronavirus (BCV) to be analysed in one assay. A lysate of HRT-18 cells infected with the L9 strain of BCV was found to have a higher RDE:HA ratio than purified virus. At 4 degrees C the lysate induced an HA pattern which completely disappeared upon raising of the temperature to 37 degrees C. This L9-infected cell lysate was used to determine the HA inhibition (HAI) titres of MAbs directed against the surface glycoproteins S and HE of BCV. Thereafter, the test plates were incubated at 37 degrees C to enable the ability of the MAbs to prevent elution of virus from BCV-erythrocyte complexes to be assessed. No inhibition of RDE was detectable with MAbs against glycoprotein S, which had HAI titres ranging from 1:16 to 1:128. On the other hand, MAbs directed against glycoprotein HE had similar HAI titres, but they inhibited elution of 8 HA units of BCV at titres of up to 1:65,000. PMID- 1940871 TI - Expression of the tobacco mosaic virus movement protein using a baculovirus expression vector. AB - A cDNA clone of the tobacco mosaic virus 30K movement protein (MP) gene was constructed and introduced into an Autographa californica nuclear polyhedrosis baculovirus expression vector. Infection of Spodoptera frugiperda cells with the vector resulted in the synthesis of low levels of MP, which was detected by anti MP serum as two closely related species of Mr approximately 34K and a third species of 32K. The authenticity of the recombinant MP was confirmed by comparison of the protein, on the basis of migration during SDS-PAGE, with authentic MP from several sources. It appeared that the recombinant MP was not modified by N-linked glycosylation, but was phosphorylated. The recombinant MP was produced in both a phosphorylated and an unphosphorylated state and the former species was shown to comigrate with plant-expressed MP during SDS-PAGE. PMID- 1940872 TI - Nucleotide sequences of genome segments S8, encoding a capsid protein, and S10, encoding a 36K protein, of rice gall dwarf virus. AB - The nucleotide sequences of DNAs complementary to the eighth (S8) and the tenth (S10) largest of the 12 genome segments of rice gall dwarf virus (RGDV) were determined. The S8 and S10 segments consist of 1578 and 1198 nucleotides, each with a single open reading frame extending for 1278 nucleotides from nucleotide 21, and 960 nucleotides from nucleotide 22, respectively. S8 encodes a polypeptide of 426 amino acids with an Mr of 47419. The amino acid sequences of several peptide fragments of the major outer capsid protein reported as 45K were contained in the predicted polypeptide. This protein, renamed the 47K protein, showed high homology with the outer capsid proteins of rice dwarf virus (RDV) and wound tumour virus (WTV); there was 56, 52 and 48% amino acid sequence identity between RGDV and WTV, RGDV and RDV, and RDV and WTV, respectively. S10 had the coding potential for a polypeptide of 320 amino acids with an Mr of 36,095 (36K protein), which exhibits 32% and 35% amino acid sequence identity with the predicted translation product of RDV S9 and the P9 capsid protein encoded by WTV S11, respectively. The conserved terminal sequences 5' GG...GAU 3' which are present in all genome segments of WTV and RDV so far analysed, and in S9 of RGDV, were also found in RGDV S8 and S10. This conserved sequence together with the segment-specific inverted repeats found in the terminal sequence of RGDV S8 and S10 are thus characteristic structures common to all three phytoreoviruses. The nucleotide sequence of the region surrounding the inverted repeats was more similar between RGDV and WTV than between RGDV and RDV. PMID- 1940874 TI - Analysis of the potential promoter sequences of African cassava mosaic virus by transient expression of the beta-glucuronidase gene. AB - DNA fragments from promoter regions of the geminivirus, African cassava mosaic virus, were cloned into pG1, a vector based on pUC18, producing transcriptional fusions with the beta-glucuronidase (GUS) gene and nopaline synthase termination sequence. The activity of each promoter construct was assessed by analysing the transient expression of GUS in Nicotiana clevelandii protoplasts. The results demonstrated that constructs containing the common region of DNA A showed much stronger promoter activity in the complementary sense than in the viral sense. These results were supported by the analysis of promoter activity in transgenic N. benthamiana plants. In comparison, in protoplasts a region upstream of the AC2 open reading frame was shown to have moderate promoter activity. Unlike DNA A, the complementary sense DNA B promoter constructs had weak activity; the viral sense DNA B promoter constructs appeared to be regulated by host factors. The implications of these results for the regulation of early and late genes are discussed. PMID- 1940873 TI - Use of the asymmetric polymerase chain reaction and DNA sequencing to determine genetic variability of bean golden mosaic geminivirus in the Dominican Republic. AB - A combination of the polymerase chain reaction (PCR), asymmetric PCR (A-PCR) and DNA sequencing was used to determine the nucleotide sequence of a hypervariable region of the bipartite genome of bean golden mosaic geminivirus (BGMV). This region, which was part of the intergenic region of the DNA-B component, was amplified using primers designed from the nucleotide sequence of a DNA-B component clone (pDRB1) of an isolate of BGMV from the Dominican Republic (BGMV DR). pDRB1 is infectious on beans when coinoculated with the DNA-A component of BGMV-DR (pDRA1), and typical bean golden mosaic symptoms are observed on infected plants. Bean leaf tissue infected with BGMV was collected at five separate field locations in the Dominican Republic and the hypervariable region was amplified by PCR, ssDNA was produced using A-PCR, and partial nucleotide sequences were determined. The sequences of the hypervariable region from the field-collected samples ranged from 95% (one sample) to 98% (four samples) identical to the sequence of pDRB1. This contrasts with sequence identities of 86, 75 and 46% between the pDRB1 hypervariable region and the hypervariable regions of BGMV isolates from Guatemala, Puerto Rico and Brazil respectively, and 42% with bean dwarf mosaic geminivirus. These results indicate that Dominican Republic isolates of BGMV are very similar and should be considered isolates of the same virus (BGMV-DR), and that the infectious clones of BGMV-DR are representative of BGMV isolates in the Dominican Republic. The procedures described for DNA extraction from leaf tissue and for production of high quality ssDNA using PCR and A-PCR are rapid and efficient and could be applied to studies of variability and epidemiology of other viruses. PMID- 1940875 TI - Detection of the movement protein of red clover necrotic mosaic virus in a cell wall fraction from infected Nicotiana clevelandii plants. AB - The movement protein of red clover necrotic mosaic virus (RCNMV) was expressed in Escherichia coli as a fusion with a maltose-binding protein using the vector pMAL cRI and used to produce an antiserum. The RCNMV movement protein was detected in a cell wall fraction obtained from infected Nicotiana clevelandii leaf tissue by immunoblotting using the movement protein antiserum. The movement protein could be detected 6 h after inoculation and reached a maximum after 24 h. In contrast, the virus capsid protein, detected in a soluble fraction by immunoblotting using a capsid antiserum, continued to increase for 72 h after inoculation. PMID- 1940877 TI - Hepatitis delta virus cDNA sequence from an acutely HBV-infected chimpanzee: sequence conservation in experimental animals. AB - Hepatitis delta virus (HDV) RNA was isolated from the serum of a chimpanzee acutely infected with hepatitis B virus (HBV) and superinfected with HDV. Interference of HDV with HBV resulted in decreased HBV DNA levels in the serum. This interference did not change the size of the two HBV specific RNAs present in the liver of the chimpanzee. The complete cDNA sequence of the HDV RNA (5th passage) was determined. Comparison of this cDNA sequence with our previously published sequence (4th passage), located in the variable domain of HDV, was highly conserved. The HDV strain used for these infections originated from a human HDV isolate also used for five to seven HDV passages in chronic HBV carrier chimpanzees (subtypes adw and ayw) or woodchucks chronically infected with woodchuck hepatitis virus (WHV). The complete HDV cDNA sequence showed an extreme conservation (up to 99.8% homology) with the previously published animal-derived HDV cDNA sequences irrespective of passage number and animal species. In contrast a markedly lower homology (85-89%) was found when compared with 3 human-derived HDV cDNA sequences. Comparison of our complete cDNA sequence with the human derived cDNA sequences showed that the nucleotide changes in the human-derived isolates were restricted to specific regions on the genome and to specific basepair substitutions. The hepatitis Delta antigen (HDAg) is highly conserved both in the human- and animal-derived cDNA sequences showing mainly conservative amino acid changes. PMID- 1940878 TI - Persistence of HIV-1 silent infection in seronegative subjects at high risk. AB - Twenty regular sexual partners of HIV-1 infected subjects, without detectable human immunodeficiency virus (HIV-1) antibody and positive for HIV-1 genome by in situ hybridization (ISH), were selected and studied longitudinally for 6-36 months to estimate the duration of silent infection. During the follow-up period, 10 showed atypical Western Blot (WB) patterns. Two seronegative partners seroconverted. Rapid progress to AIDS was observed in 7 seropositive subjects. PMID- 1940879 TI - Prevalence of hepatitis C virus infections among heterosexuals with multiple partners. AB - A study among heterosexual men and women with multiple sexual partners was carried out to assess the seroprevalence of antibody against hepatitis C virus (HCV). The 468 participants were recruited among visitors to the Clinic for Sexually Transmitted Diseases in Amsterdam. Sera were tested by an enzyme-linked immunosorbent assay (ELISA; Ortho), a recombinant-based immunoblot assay (RIBA; Chiron), and the polymerase chain reaction (PCR). A total of 468 persons were tested, and seven (1.5%) were found ELISA positive. Another 25 (5%) were ELISA indeterminate. Six of the seven ELISA-positive cases were RIBA positive. Further serum samples from five HCV ELISA-positive persons were tested by PCR, and four were found to be positive. The HCV ELISA-positive/RIBA-indeterminate reaction was PCR negative. None of the 17 RIBA-tested sera of the ELISA-indeterminate group yielded a positive result. There was a good correlation between an ELISA optical density/cut-off ratio greater than 2 and a positive RIBA result. The risk factor for HCV appeared to be the type of sexual partner, i.e., belonging to a "high risk" group for human immunodeficiency virus infection and origin from hepatitis B-endemic countries. It is concluded that HCV may be transmitted through heterosexual contact but probably with low efficiency. PMID- 1940876 TI - Outbreak of acute hepatitis E virus infection among military personnel in northern Ethiopia. AB - An outbreak of acute hepatitis E virus (HEV) infection occurred from October 1988 to March 1989 in military camps in northern Ethiopia. The epidemic was waterborne and entirely confined to military men, of whom 423 hospitalized, icteric patients were studied. The clinical course was mild and short, without any fulminant hepatitis or death. All sera tested for anti-HAV-IgM were negative and among 54 (13%) patients who were positive for HBsAg, 7 (2%) were positive for anti-HBc IgM. On the other hand, 28 of 30 (93%) patients had antibodies against hepatitis E virus (anti-HEV) in contrast to 1 of 29 (3%) asymptomatic controls (P less than .01). The need for an easily available, inexpensive serologic test for HEV infection, protection of water supplies from fecal contamination, adequate chlorination and/or boiling of drinking water, and health education about personal and environmental hygiene, especially in communities at high risk, is emphasized. PMID- 1940880 TI - Removal of parvovirus B19 from contaminated factor VIII during fractionation. AB - A solution of pooled cryo-precipitate for preparing factor VIII (F VIII) by the solvent/detergent method was contaminated experimentally with parvovirus B19 positive plasma to evaluate virus reduction achieved by the final steps of the F VIII production process. Virus reduction was at least 2 logs of the total amount of B19 virus added to the pooled cryo-precipitate. The major amount of B19 virus was detected in the solution used to regenerate the F VIII-selective anion exchange chromatography column. A few viral particles were detected in the final F VIII concentrate before filtration but these were aggregates and were removed by filtration, and in the solution used to regenerate the anion exchange resin. It is not known whether the residual viral DNA present in the final product represents infectious or inactivated particles. PMID- 1940881 TI - Treatment with human gamma interferon of chronic hepatitis B: comparative study with alpha interferon. AB - A pilot study was designed to determine the tolerance and effectiveness of natural or recombinant gamma interferon in patients with chronic hepatitis B. Sixteen patients received 0.5 to 3.0 million units (MU) per day of gamma interferon (IFN-gamma) for 7 days. Nineteen chronic hepatitis B patients who were treated with 5-6 MU leukocyte-derived alpha interferon (IFN-alpha) daily served as controls. All completed the treatment schedule. IFN-gamma exerted mild, but significant inhibitory effects (P less than .05) on serum DNA polymerase levels. However, the changes were significantly less (P less than .001) than those seen with IFN-alpha therapy when compared with percent change from basal values. In contrast, serum 2', 5'-oligoadenylate synthetase (2-5 AS) activities were markedly enhanced to a similar extent during therapy with both IFNs. Serum beta 2 microglobulin values were significantly increased by administration with both IFNs, although higher values were seen with IFN-gamma. Five patients received 1 MU IFN-gamma for 28 consecutive days and their HBeAg levels similarly decreased as those seen in patients treated with IFN-alpha. Side effects seemed to be greater during IFN-gamma therapy than IFN-alpha despite the lower doses used. The antiviral effect on serum HBV levels appeared less with IFN-gamma than with IFN alpha. Alternatively immunomodulatory functions may have been enhanced with IFN gamma in patients with chronic HBV infection. PMID- 1940882 TI - Direct measurement of viraemia in patients infected with HIV-1 and its relationship to disease progression and zidovudine therapy. AB - Cell-free human immunodeficiency virus type-1 (HIV-1) was precipitated from archival serum with polyethylene glycol (PEG), and HIV-1 RNA was detected and quantified by reverse transcription and amplification in a nested polymerase chain reaction (PCR). The assay of end-point dilutions cDNA in nested PCRs allowed an estimation of the minimum RNA copies per unit volume of serum. RNA titres correlated with the classification of HIV-1 infection by CDC disease groups (30 patients). The geometric mean titres of HIV-1 serum RNA from patients grouped by disease stage gave minimum estimates of 340 and 400 virions per millilitre of serum in CDC groups II and III (n = 6 and 10, respectively) and 4,240 virions per millilitre in CDC group IV (n = 14). An overall fall in viral titre measured in this way was observed in 3 patients during zidovudine treatment. HIV-1 titres increased in a further 4 patients when therapy was interrupted, stopped, or complicated by secondary infection. PMID- 1940883 TI - Analysis of a pregnancy-screening and neonatal-immunization program for hepatitis B in Hamilton, Ontario, Canada, 1977-1988. AB - During the 12 years from January, 1977, to December, 1988, the Hamilton Centre of the Canadian Red Cross Society (CRCS) Blood Transfusion Service screened 98,712 pregnant patients for hepatitis B surface antigen (HBsAg) and identified 120 positives (0.12%). The number of positives ranged from six to 16 per year. We were able to trace and enroll 65 mothers (54%) and 96 of their children in the follow-up study. The majority of the women were between 20 and 30 years of age (95.4%) and married (86%), and about one-half were employed outside the home. Sixty-five percent were white and 34% Asian, and 20 countries were listed as their places of origin. Hepatitis B immune globulin (HBIG) was available for neonatal immunization since 1977 and combined with vaccine since 1982. Of the 96 candidates for HBIG, 60 (63%) received HBIG within 24 hr, one after 3 months, four unknown, and 31 did not receive it. Of the 56 candidates for vaccination from 1982 to 1989, 26 (46%) received three doses, seven had two doses, eight had one dose, one was unknown, and 14 had none. HBsAg tests were performed on 69 children (71.8%) and anti-HBs on 61 (63.5%). Four of the children are HBsAg positive, 31 have anti-HBs, and 31 have no detectable antibodies. All four HBsAg positives had not received vaccine, and only one had received HBIG. Of the children positive for hepatitis B surface antibodies, five had received no immunization and therefore had been subclinically infected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940884 TI - Hepatitis B virus DNA in sera of virus carriers positive exclusively for antibodies to the hepatitis B core antigen. AB - The prevalence of serum HBV DNA in individuals positive for anti-HBc alone was determined by the polymerase chain reaction in two groups with endemic HBV infection from Canton (group A) and Hainan (group B), provinces of China. Twenty one out of 294 individuals in group A (7.2%) and 193 out of 1995 in group B (9.7%) were positive for anti-HBc but negative for other markers of ongoing or past HBV infection (HBsAg and anti-HBs). HBV DNA was detected in 6/21 sera in group A (28.6%) and 68/193 in group B (35.2%) in their initial serum specimen. One of the six HBV-DNA-positive individuals in group A became negative after 6 months and four of the 58 positive in group B became negative at 4 years of follow-up. All of the individuals remained positive for anti-HBc and negative for anti-HBs, but one of them became positive for HBsAg on follow-up. None of the anti-HBc- and HBV-DNA-positive subjects had symptoms of liver diseases. They were, therefore, defined as chronic asymptomatic HBV carriers with undetectable HBsAg. This type of carrier should be added to the typical HBsAg-positive carrier, who constitutes about 10-15% of the general Chinese population, to give a more complete estimate of asymptomatic HBV carriers in China. PMID- 1940885 TI - Influence of volume expansion on capillary transport in the gut of Pichinde virus infected strain 13 guinea pigs. AB - Hydropenic strain 13 guinea pigs (GP13) injected with Pichinde virus show marked jejunal capillary disruption determined by a reduction in protein reflection coefficient (sigma) [Katz and Starr, 1990]. These studies examined whether this is reversed by a 2% Ringer's expansion, and whether anorexia may contribute to reduced sigma. GP13 were either infected or given a 60% expected ad lib diet, and were studied while under a 2% Ringer's expansion. The results showed 1) infected GP13 separated into groups with either a persistently low sigma (volume unresponsive) or a normal sigma (volume responsive), but no obvious feature of the animals could predict responsiveness; 2) caloric restriction had minimal to no effect on sigma; and 3) both responsive and unresponsive GP had increased heart, lung, and kidney weights. Volume expansion may have salutary effects in some infected GP13, and this is probably due to pressure mediated effects on the capillary wall. The findings support the possibility that conservative management of hemorrhagic fevers may directly ameliorate capillary leak. PMID- 1940887 TI - Three forms of somatization in primary care: prevalence, co-occurrence, and sociodemographic characteristics. AB - Three definitions of somatization were operationalized: (a) high levels of functional somatic distress, measured by the Somatic Symptom Index (SSI) of the Diagnostic Interview Schedule; (b) hypochondriasis measured by high scores on a measure of illness worry in the absence of evidence for serious illness; and (c) exclusively somatic clinical presentations among patients with current major depression or anxiety. Of 685 patients attending two family medicine clinics, 26.3% met criteria for one or more forms of somatization. While DSM-III somatization disorder had a prevalence of only 1% in this population, 16.6% of the patients met abridged criteria for subsyndromal somatization disorder (SSI 4,6). Hypochondriacal worry had a prevalence of 7.7% in the clinic sample. Somatized presentations of current major depression or anxiety disorder had a prevalence of 8%. The three forms of somatization were associated with different sociodemographic and illness behavior characteristics. A majority of patients met criteria for only one type of somatization, suggesting that distinct pathogenic processes may be involved in each of the three types. PMID- 1940886 TI - Quantitation of HIV: correlation with clinical, virological, and immunological status. AB - A quantitative assay has been used to measure titres of infectious HIV in peripheral blood of symptomatic and asymptomatic patients. Viral titres were assessed in conjunction with virological and immunological status of patients including measurement of p24 antigen, antibody responses to structural (gp41, p24) and regulatory gene products (NEF, REV, TAT, and VIF), determination of beta 2 microglobulin levels and enumeration of lymphocyte subsets. Titres of HIV were significantly higher among symptomatic than asymptomatic patients. Viral load was closely associated with the number of CD4+ cells, the proportion of these cells harbouring HIV increasing with disease progression. Higher titres of infectious HIV among symptomatic patients was also associated with p24 antigenaemia and decreased antibody responses to NEF. PMID- 1940888 TI - Adult vulnerability for psychiatric disorders: interactive effects of negative childhood experiences and recent stress. AB - The effects of negative childhood experiences on adult psychiatric status remain unclear because of inconsistent findings in previous studies. In this study, we examine the extent to which parental separation/divorce before the age of 10, parental death before the age of 10, and self-reports of parental mental illness during early childhood interact with recent stressful life events to increase the probability of multiple psychiatric disorders and psychiatric symptoms during adulthood. Data are from a stratified random sample of 3801 adults residing in a five-county catchment area in North Carolina. The Diagnostic Interview Schedule was used to measure psychiatric disorders and symptoms during the 6 months prior to the interview. Regression analyses were used to determine whether negative childhood experiences interact with recent stressful life events to increase the probability of psychiatric disorders or symptoms, with other risk factors statistically controlled. Results suggest that: a) parental mental illness increases the likelihood that stressful life events will result in depression, although it is unclear whether this increased vulnerability is due to genetic or environmental factors; b) parental separation/divorce interacts with stressful life events to increase vulnerability to alcohol problems and psychiatric disorders more generally; and c) parental death does not interact with recent events to affect the likelihood of psychiatric problems. PMID- 1940889 TI - Sleep and dreaming in Holocaust survivors. Dramatic decrease in dream recall in well-adjusted survivors. AB - Sleep data were obtained on 12 well-adjusted and 11 less-adjusted Holocaust survivors and on 10 control subjects. Each was also awakened from rapid eye movement sleep for dream recall. The less-adjusted survivors had more prolonged sleep latency than the well-adjusted and the control groups and lower sleep efficiency than the control subjects. The well-adjusted group had a significantly lower dream recall rate (33.7%) than the less-adjusted (50.5%) and control groups (80%). There were also significant between-groups differences in dream structure and dream content, in the direction of less complex and less salient dreams in the well-adjusted survivors. It is suggested that the decrease in dream recall is one of the forms of long-term adjustment to severe traumatic events. PMID- 1940891 TI - Life course of depressive illness and characteristics of current episode in patients with double depression. AB - It has been suggested recently that major depression and concurrent chronic minor depression, or "double depression" (DD), may have a different course and presentation from major depression alone (MDA). The present study compares 41 patients with DD and 60 patients with MDA for differences in life course of depressive illness and characteristics of the current depressive episode. Patients with DD, as compared with patients with MDA, had an earlier age of onset of mood disturbance, more episodes of major depression, and more frequent concurrent anxiety disorders. However, patients with DD were not significantly different from patients with MDA who had greater than a 6-month history of mood disturbance, with regard to life course of illness variable. The characteristics of current depression in patients with DD and MDA were not significantly different. The clinical and theoretical implications of these findings are discussed. PMID- 1940890 TI - Prevalence and correlates of depressive symptoms among former prisoners of war. AB - Studies of former prisoners of war (POWs) provide valuable insights into posttraumatic adaptation because they gather information from a large population who survived the traumatic experiences of military captivity. Previous studies of POWs have shown elevated rates of psychiatric symptoms and disorders. This report presents evidence from a longitudinal study of three large, representative, national samples of former POWs. The study finds that depressive symptomatology, as measured by the Center for Epidemiologic Studies Depression Scale, is elevated in World War II POWs from the Pacific and European theaters and in Korean conflict POWs. Decades later, depressive symptomatology is found to be strongly associated with prior treatment in captivity. Differences in depressive symptomatology among the three POW groups can be attributed to captivity-related factors and to buffering factors, such as age at capture and education. PMID- 1940892 TI - A controlled quantitative study of facial expression in Parkinson's disease and depression. AB - A microcomputer-based approach to the quantification of facial expression was used to measure and compare the smiling behavior of a group of Parkinson's disease sufferers, a group of patients with major depression, and a control group of comparable age. Subjects were asked to view a series of amusing slides and their expressions were recorded. The most animated smile for each subject was chosen for analysis and scores on 12 computer-generated measures were obtained using the Facial Expression Measurement program. These measures are end-lip measure, mouth width measure, mouth-opening measure, mid-top measure, mid-lower lip measure, top lip-thickness measure, lower lip-thickness measure, eye-opening measure, top eyelid/iris intersect measure, lower eyelid/iris intersect measure, inner eyebrow measure, and mid-eyebrow measure. The depressed group differed significantly from the other groups, with higher scores on end-lip measure, mid top lip measure, and mid-eyebrow measure. All subjects completed the Levine Pilowsky Depression Questionnaire. The depressed patients obtained higher depression scores than the parkinsonian group, who in turn had significantly higher depression scores than the control group. The depression score was correlated with end-lip measure, mouth width measure, mid-top lip measure, eye opening measure, and mid-eyebrow measure in the population as a whole. A significant negative correlation emerged between the depression score and mid eyebrow measure in the depressed group. Both the depressed group and the parkinsonian group were found to smile significantly less often during the slide session when compared with the control group. These results are discussed in the light of earlier findings. PMID- 1940893 TI - Screening for psychosis in the general population with a self-report interview. AB - This analysis applies methods of screening to the problem of psychosis. A probability sample of 810 individuals from the Eastern Baltimore Mental Health Survey was interviewed in the self-report modality with the Diagnostic Interview Schedule and shortly thereafter by a psychiatrist. It is shown that a configuration of responses in the self-report modality can screen moderately well for psychosis, as measured by psychiatrists in the clinical modality. PMID- 1940894 TI - Personality and sexual functioning of transvestitic fetishists and other paraphilics. AB - Utilizing the NEO Personality Inventory (NEO-PI) and the Derogatis Sexual Functioning Inventory (DSFI), 24 transvestitic fetishists (TVs) were compared with a similar clinic-evaluated group of 26 other paraphilics (OPs). The data replicated previous results and extended them by showing that TVs did not differ from OPs on most dimensions of the NEO-PI and the DSFI. Both groups were significantly higher on neuroticism and significantly lower on agreeableness than the NEO-PI male normative population. The other paraphilic group tended to score lower on conscientiousness than the TVs and the normative comparison group. For nine of the 10 DSFI variables, there were no significant differences between the TVs and the OPs. The TVs were significantly higher than the OPs on role identity, indicating a more feminine identification. Both the TVs and OPs reported elevated levels of fantasy. The implications of these findings suggest that, in general, TVs and OPs are more similar than they are different, with a common personality profile and a similar pattern of sexual functioning. PMID- 1940895 TI - Combination of treatments for attention deficit hyperactivity disorder in adults. AB - Three adults with DSM-III-R diagnoses of attention deficit hyperactivity disorder were treated with a combination of a psychostimulant and nadolol. Previous treatment with only a psychostimulant had not been effective or had not been tolerated. The combination treatment resulted in an increase in attention and focusing capacities, along with a decrease in anxiety, impulsiveness, and somatic discomfort. These improvements suggest an effective regimen for treatment resistant adults with attention deficit hyperactivity disorder. PMID- 1940896 TI - Bipolar disorder associated with Turner's syndrome. PMID- 1940897 TI - Assault increases the cost of care among inpatient veterans with schizophrenia. PMID- 1940898 TI - Structure and antimicrobial activity of some new azopyrazolone chelates of Ni(II) and Cu(II) acetates, sulfates, and nitrates. AB - Four coordinate Ni(II) and Cu(II) chelates formed by reaction of two azopyrazolone derivatives with metal sulfate, acetate, or nitrate are described. It is concluded that the ligands possess tautomeric equilibria and can coordinate to the metal ion as neutral or monobasic bidentates. The so-obtained complexes are characterized by elemental and thermal analyses, IR and electronic spectra, as well as conductivity measurements. A pseudo-tetrahedral polymeric structure is proposed for all the complexes in which the acetate, nitrate, or sulfate is attached to the metal ion in the bridging bidentate mode. It is observed that the chelates formed are more potent as antimicrobial agents than the free ligands. PMID- 1940899 TI - Palladium, platinum, cadmium, and mercury complexes with neutral isoorotic and 2 thioisoorotic acids: IR and NMR spectroscopies, thermal behavior and biological properties. AB - Seven complexes containing neutral isoorotic and 2-thioisoorotic acids, as well as thiocyanate and chloride anions as lignands, have been synthesized and characterized by means of both spectral (IR, 1H, and 13C NMR) and thermal (TG and DSC) methods, as well as conductivity measurements. Spectral data suggest that any binding metal-ligand mode for uracil derivatives is not easy to propose. Therefore, isoorotic ligands must link through some oxygen atom. Likewise, 2 thioisoorotic acid seems to be [N,S] bonded in Pd(II) and Pt(IV) complexes, whereas for Hg(II) complex a distorted tetrahedral HgCl2S2 structure has been proposed. In the cadmium complex, the metal ion exhibits a CdCl2O2 coordination sphere. Antimicrobial activities of the complexes against Pseudomonas sp, E. coli, Proteus sp, Salmonella sp, Micrococcus sp, Staphylococcus sp, Bacillus sp and Candida sp were performed as a previous step in the study of their biological activity. PMID- 1940900 TI - Changes in poly[d(T-G).d(C-A)] chirality due to Hg(II)-binding: circular dichroism (CD) studies. AB - The conformation of poly[d(T-G).d(C-A)] in aqueous solution (0.1 M NaClO4, 5 mM cacodylic acid buffer, pH 6.9) was studied by circular dichroism (CD) spectroscopy in the ultraviolet. The conformation of the polynucleotide, as reflected by its chiroptical signature, changes in a highly cooperative fashion in the presence of Hg(ClO4)2. The CD changes signal transitions first from the B to a modified B-state (B*), or to a non-B structure termed X, and finally to a form that is presumably Z. The alterations are totally reversible subsequent to the removal of mercury with the help of a suitable complexing agent such as sodium cyanide, indicating that mercuration does not disrupt Watson-Crick hydrogen bonding to any extent. PMID- 1940901 TI - Preparation, characterization, and antitumor activity of water-soluble aminoalkanol platinum(II) complexes. AB - A new series of highly water-soluble aminoalkanol platinum(II) complexes have been synthesized and characterized by elemental analysis, conductance, IR, and 195Pt NMR. Preliminary in vitro and in vivo screening tests for antitumor activities of these complexes against L1210 murine leukemia were performed. In general, these compounds were far less cytotoxic than cisplatin and possessed only a moderate degree of antitumor activity. PMID- 1940902 TI - Regulation of 109Cd2+ uptake into isolated neurohypophysial peptidergic nerve terminals. AB - Cadmium (109Cd2+) uptake was studied in a preparation of isolated neurohypophysial nerve terminals. By use of a filter separation method, together with a permeabilizing agent (Triton X-100), two cellular Cd2+ pools have been distinguished. The uptake into the intraterminal pool was governed mainly by a process that displayed saturable kinetics, with a Vmax of 0.15 nmol of Cd2+/mg of protein/min and a Km of 0.18 mM, consistent with a transport system. The superficially bound Cd2+ pool (Triton insensitive), which represented 30-50% of the total Cd2+ bound to the cellular system, was very sensitive to the ionic composition of the incubation medium. Reducing the extracellular Ca2+ or Na+ concentration caused a significant increase in the size of the Triton-insensitive Cd2+ pool. Whereas Na+ did not affect Cd2+ uptake, Ca2+ induced a small, but significant, increase of Cd2+ uptake into the terminals. It is concluded that there is a significant intraterminal uptake of Cd2+, which could explain several physiological effects of this ion. PMID- 1940903 TI - Age-dependent increase in neuropeptide Y gene expression in rat adrenal gland and specific brain areas. AB - Age-dependent changes in the expression of neuropeptide Y (NPY) peptides and prepro-NPY mRNA (NPY mRNA) were studied in rat adrenal gland and brain areas by means of radioimmunoassay, immunohistochemistry, and northern blot analysis. In the adrenal gland, NPY immunoreactivity (NPY-I) increased by 80-fold, mainly in the chromaffin cells, during aging (from 7 to 33 weeks old). The increase in NPY I was accompanied by a concomitant increase in the content of NPY mRNA (800 bases in size, by 16-fold) and putative NPY pre-mRNA, a result suggesting that this increase results from that in NPY gene expression, probably at the level of transcription. In contrast, in some brain areas, such as striatum and medulla oblongata plus pons, NPY-I decreased in an age-dependent manner, whereas NPY mRNA abundances in these areas increased by twofold with age (from 7 to 33 weeks old). The opposite changes between NPY and NPY mRNA content in specific brain areas suggested the accelerated turnover/degradation of NPY peptide in the brain areas. Furthermore, beta-actin mRNA abundance did not change in rat adrenal gland and brain areas during aging. Thus, the characteristic age-related increase in NPY gene expression in rat adrenal gland and some brain areas seems to be important for physiological regulation of some neuronal functions, such as blood pressure, in aged animals. PMID- 1940904 TI - Ryanodine inhibits caffeine-evoked Ca2+ mobilization and catecholamine secretion from cultured bovine adrenal chromaffin cells. AB - The effects of ryanodine, a selective inhibitor of the Ca(2+)-induced Ca2+ release mechanism, on caffeine-evoked changes in cytosolic Ca2+ concentration ([Ca2+]i) and catecholamine secretion were investigated using cultured bovine adrenal chromaffin cells. Caffeine (5-40 mM) caused a concentration-dependent transient rise in [Ca2+]i and catecholamine secretion in Ca2+/Mg(2+)-free medium containing 0.2 mM EGTA. Ryanodine (5 x 10(-5) M) alone had no effect on either [Ca2+]i or catecholamine secretion. Although the application of ryanodine plus caffeine caused the same increase in both [Ca2+]i and catecholamine secretion as those induced by caffeine alone, ryanodine (4 x 10(-7) - 5 x 10(-5) M) irreversibly prevented the increase in both [Ca2+]i and catecholamine secretion resulting from subsequent caffeine application over a range of concentrations. The secretory response to caffeine was markedly enhanced by replacement of Na+ with sucrose in Ca2+/Mg(2+)-free medium, and this enhanced response was also blocked by ryanodine. Caffeine was found to decrease the susceptibility of the secretory apparatus to Ca2+ in digitonin-permeabilized cells. These results indicate that caffeine mobilizes Ca2+ from intracellular stores, the function of which is irreversibly blocked by ryanodine, resulting in the increase in catecholamine secretion in the bovine adrenal chromaffin cell. PMID- 1940905 TI - Tellurium blocks cholesterol synthesis by inhibiting squalene metabolism: preferential vulnerability to this metabolic block leads to peripheral nervous system demyelination. AB - Inclusion of 1.1% elemental tellurium in the diet of postweanling rats produces a peripheral neuropathy due to a highly synchronous primary demyelination of sciatic nerve; this demyelination is followed closely by remyelination. Sciatic nerves from animals fed tellurium for various times were removed and incubated ex vivo for 1 h with [14C]acetate, and radioactivity incorporated into individual lipid classes was determined. In nerves from rats exposed to tellurium, there was a profound and selective block in the conversion of radioactive acetate to cholesterol. Another radioactive precursor, [3H]water, gave similar results. We suggest that tellurium feeding inhibits squalene epoxidase activity and that the consequent lack of cholesterol destabilizes myelin, thereby causing destruction of the larger internodes. Ex vivo incubation experiments were also carried out with liver slices. As with nerve, tellurium feeding caused accumulation in squalene of label from radioactive acetate, whereas labeling of cholesterol was greatly inhibited. Unexpectedly, however, incorporation of label from [3H]water into both squalene and cholesterol was increased. Relevant is the demonstration that liver was the primary site of bulk accumulation of squalene, which accounted for 10% of liver dry weight at 5 days. Thus, accumulation of squalene (and other mechanisms, possibly including up-regulation of cholesterol biosynthetic pathways) drives squalene epoxidase activity at normal levels in liver even in the presence of inhibitors of this enzyme. This is reflected by continuing incorporation of [3H]water into cholesterol; incorporation of this precursor takes place at many of the postsqualene biosynthetic steps for sterol formation. [14C]Acetate entering the sterol pathway before squalene in liver is greatly diluted in specific activity when it reaches the large squalene pool, and thus increased squalene epoxidase activity does not transfer significant 14C label to sterols. In contrast to the situation with liver, synthesis of sterols is markedly depressed in sciatic nerve, and squalene does not accumulate to high levels. PMID- 1940906 TI - Tellurium-induced alterations in 3-hydroxy-3-methylglutaryl-CoA reductase gene expression and enzyme activity: differential effects in sciatic nerve and liver suggest tissue-specific regulation of cholesterol synthesis. AB - The demyelination of peripheral nerves that results from exposure of developing rats to tellurium is due to inhibition of squalene epoxidase, a step in cholesterol biosynthesis. In sciatic nerve, cholesterol synthesis is greatly depressed, whereas in liver, some compensatory mechanism maintains normal levels of cholesterol synthesis. This tissue specificity was further explored by examining, in various tissues, gene expression and enzyme activity of 3-hydroxy-3 methylglutaryl-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Exposure to tellurium resulted in pronounced increases in both message levels and enzyme activity in liver, the expected result consequent to up regulation of this enzyme in response to decreasing levels of intracellular sterols. In contrast to liver, levels of mRNA and enzyme activity in sciatic nerve were both decreased during the tellurium-induced demyelinating period. The temporal pattern of changes in 3-hydroxy-3-methylglutaryl-CoA reductase message levels in sciatic nerve seen following exposure to tellurium was similar to the down-regulation seen for mRNA specific for PNS myelin proteins. Possible mechanisms for differential control of cholesterol biosynthesis in sciatic nerve and liver are discussed. PMID- 1940907 TI - A fast axonally transported protein of the frog sciatic sensory axons undergoes similar qualitative changes during regeneration in vitro and in vivo. AB - The adult frog sciatic sensory neurons have been shown to regenerate in vitro. If a crush injury is made at the beginning of culture, regeneration starts after 3.4 days and proceeds at a rate of approximately 0.8 mm/day for several days. Two dimensional gel electrophoresis was used to study the patterns of radiolabeled, fast axonally transported proteins during the first 7 days of regeneration. Interest was focused on one protein, referred to as rrp31 (regeneration-related protein 31), which changed in apparent pI from 4.9 to 5.3 when the outgrowth of new fibers started. The change was noticeable 3 days after injury and became prominent during day 5 of culturing. By day 7 the pI changed again, this time toward the original value. The in vitro results were supported by experiments in vivo. In this case the change occurred earlier, with a peak only 3 days after injury, after which the pI decreased. If adenosine at 1 mM was included in the culturing medium, the outgrowth of sensory axons was inhibited in a nontoxic way, and the pI changes of rrp31 were prevented. The temporal nature of the pI changes suggests a role for rrp31 in the initiation of the regeneration process. PMID- 1940908 TI - Axonal transport reversal of acetylcholinesterase molecular forms in transected nerve. AB - Reversal of anterograde rapid axonal transport of four molecular forms of acetylcholinesterase (AChE) was studied in chick sciatic nerve during the 24-h period following a nerve transection. Reversal of AChE activity started approximately 1 h after nerve transection, and all the forms of the enzyme, except the monomeric ones, showed reversal of transport. The quantity of enzyme activity reversed 24 h after transection was twofold greater than that normally conveyed by retrograde transport. We observed no leakage of the enzyme at the site of the nerve transection and no reversal of AChE activity transport in the distal segment of the severed nerve, a result indicating that the material carried by retrograde axonal transport cannot be reversed by axotomy. Thus, a nerve transection induces both quantitative and qualitative changes in the retrograde axonal transport, which could serve as a signal of distal injury to the cell body. The velocity of reverse transport, measured within 6 h after transection, was found to be 213 mm/day, a value close to that of retrograde transport (200 mm/day). This suggests that the reversal taking place in severed sciatic nerve is similar to the anterograde-to-retrograde conversion process normally occurring at the nerve endings. PMID- 1940909 TI - Pergolide presynaptically inhibits calcium-stimulated release of gamma aminobutyric acid. AB - The release of gamma-aminobutyric acid (GABA) in rat dorsolateral striatum was studied using in vivo microdialysis. Dialysis was conducted 2 days after probe implantation in awake, freely moving rats using a modified Ringer solution. Calcium induced a reversible increase in GABA release that was abolished by tetrodotoxin but was only slightly attenuated by a maximally effective dose of pergolide, a D2 receptor agonist. It was thus concluded that pergolide inhibits calcium-stimulated release of GABA presynaptically by a mechanism distinct from that of tetrodotoxin. PMID- 1940910 TI - Rapid internalization and intracellular metabolic processing of exogenous ganglioside by cerebellar granule cells differentiated in culture. AB - Ganglioside GM1, tritiated at the level of the long chain base (sphingosine) [( Sph-3H]GM1), sialic acid (N-acetylneuraminic acid) [( NeuAc-3H]GM1), or terminal galactose [( Gal-3H]GM1) was supplied to cerebellar granule cells differentiated in vitro, and its metabolic processing was followed with pulse time. Using [Sph 3H]GM1 and [NeuAc-3H]GM1 the formation of radioactive compounds of catabolic origin (GM2, GM3, lactosylceramide, glucosylceramide, and ceramide) started being detectable at 10-15 min of pulse, whereas compounds of biosynthetic origin (GD1a, GD1b, GT1b, O-acetylated GT1b, spingomyelin, and sialoglycoprotein) appeared after 15-30 min of pulse. Using [Gal-3H]GM1 two radioactive substances were formed, GD1a and GT1b, with the former (produced by direct sialosylation of GM1) appearing after 30 min of pulse and the latter (formed by biosynthetic recycling of released galactose) appearing after 2 h. The radioactivity linked to all metabolites increased with increasing pulse time until 4 h. The percentage of GM1 taken up and subjected to metabolic processing was found to increase from 1.8% after 10 min of pulse to 12.5% after 4 h. Cerebellar granule cells were able to release enzymes of lysosomal origin, beta-D-N-acetylhexosaminidase and beta-D galactosidase, into the culture medium, with the release being markedly decreased by the absence in the medium of fetal calf serum, a condition that was used for studying exogenous GM1 uptake and metabolization. However, these enzymes exerted no activity at the pH of the culture medium, and no radioactive gangliosides, besides GM1, were detected in the culture medium during pulse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940911 TI - 1-Methyl-1,2,3,4-tetrahydroisoquinoline, decreasing in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-treated mouse, prevents parkinsonism-like behavior abnormalities. AB - In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse brain, there was no significant increase or decrease in the content of an endogenous amine, 1,2,3,4-tetrahydroisoquinoline (TIQ), which is well noted for inducing parkinsonism, whereas another endogenous amine, 1-methyl-1,2,3,4 tetrahydroisoquinoline (1-MeTIQ), was markedly reduced. This result agrees with the finding in human idiopathic parkinsonianism, confirmed by our previous research. In addition, pretreatment with 1-MeTIQ completely prevented MPTP- or TIQ-inducing bradykinesia, a symptom of parkinsonism. This study confirmed that 1 MeTIQ plays an important role in preventing the pathogenesis of parkinsonism and is a possible leading compound of anti-parkinsonism agents. PMID- 1940912 TI - Effect of unilateral perinatal hypoxic-ischemic brain injury in the rat on striatal muscarinic cholinergic receptors and high-affinity choline uptake sites: a quantitative autoradiographic study. AB - The binding characteristics and distribution of M1 and M2 muscarinic cholinergic receptors and high-affinity choline uptake sites were studied in the striatum of the rat at 3-4 and 9-12 weeks of age after exposure to unilateral perinatal hypoxic-ischemic brain injury. High-affinity choline uptake sites were labeled with [3H]hemicholinium-3, M1 receptors with [3H]pirenzepine, and M2 receptors with [3H]AF-DX 116. Saturation experiments revealed a significant decrease in the maximal binding capacity (Bmax) for [3H]pirenzepine-labeled M1 receptors in the lesioned caudate/putamen complex in immature rats with moderate brain injury, in comparison with controls. In contrast, the Bmax value for [3H]hemicholinium-3 labeled high-affinity choline uptake sites was significantly increased. No changes in dissociation constants (KD) were observed. These changes were most pronounced in the dorsolateral region of striatum. Striatal regional distribution of [3H]AF-DX 116 was not affected. In mature rats, binding of [3H]pirenzepine returned to control values, whereas [3H]hemicholinium binding showed a persistent increase (23%). The increase in [3H]hemicholinium-3 binding, as a specific marker of cholinergic nerve terminals, is consistent with our prior morphologic studies demonstrating relative preservation of cholinergic neurons and neuropil, and supports the concept that striatal cholinergic systems are resistant to hypoxic ischemic injury. PMID- 1940913 TI - Characterization of rat ARPP-21 mRNA: sequence analysis, tissue distribution, and regulation. AB - ARPP-21 (cyclic AMP-regulated phosphoprotein; Mr = 21,000) is a cytosolic neuronal phosphoprotein that is highly enriched in the striatum and in other dopaminoceptive regions of the brain. The state of phosphorylation of ARPP-21 is also regulated by vasoactive intestinal peptide in intact cells. We previously reported the sequence analysis of bovine ARPP-21 cDNA and have now characterized rat ARPP-21 cDNA to study further the molecular biology of this protein. The sequence of the coding region is 82 and 85% identical at the nucleotide and amino acid levels, respectively, between the two species. There are two major classes of clones, differing only in the lengths of their 3' untranslated ends, suggesting that the different ARPP-21 mRNAs are derived from the use of alternate polyadenylation sites. Both major mRNA species, 2.6 and 0.7 kb, are present at the highest concentration in the striatum, followed by the cortex, consistent with previous immunocytochemical results. Southern blot analysis reveals a simple hybridization pattern, consistent with the presence of a single rat gene encoding ARPP-21. The steady-state levels of the ARPP-21 mRNAs are developmentally regulated but, in the neonatal and mature animal, are not altered following 6 hydroxydopamine lesions of the substantia nigra or by pharmacologic treatments that up-regulate the D1- or D2-dopamine receptors. PMID- 1940914 TI - Evidence for an association of the 15-kDa proteolipid of mediatophore with a 14 kDa polypeptide. AB - The present report shows that mediatophore, a nerve terminal membrane protein that translocates acetylcholine on calcium action, forms a complex with a 14-kDa polypeptide. The complex was identified based on the following results. (a) A polyclonal antimediatophore antiserum that immunoprecipitates activity precipitates both the 15- and 14-kDa polypeptides. (b) After HPLC purification of mediatophore, both antigens were found in the same peak. (c) After 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonate solubilization of presynaptic membranes or of the purified mediatophore, an immunoaffinity column made with the anti-14-kDa antigen monoclonal antibody retained both the 14-kDa and the 15-kDa polypeptide. Similarly, immunoprecipitation experiments using protein A-coated beads sedimented an immunocomplex in which both antigens were found. (d) The 14 kDa antigen could be localized in the synaptosomal membrane where mediatophore and its 15-kDa component are found. PMID- 1940915 TI - GD3 prevalence in adult rat retina correlates with the maintenance of a high GD3 /GM2-synthase activity ratio throughout development. AB - Unlike neurons from avian retina and other regions of avian and mammalian brain, neurons from mammalian retina not only contain gangliosides of the gangliotetraosyl ceramide series but also maintain a prevalence of GD3, a ganglioside of the lactosylceramide series characteristic of proliferative neural cells, when they are fully differentiated. We show here that GD3 is prevalent at all developmental periods of the rat retina from birth [50% of total gangliosidic N-acetylneuraminic acid (NeuNAc)] to adult (30% of total gangliosidic NeuNAc). GD3-synthase specific activity increased about 1.5-fold from birth to day 7 and essentially plateaued thereafter. The GD3-/GM2-synthase specific activity ratio was compared in rat and chicken retina at early and late developmental stages. In chicken retina the ratio was about 0.7 at early (when GD3 is prevalent) and decreased to 0.07 at late (when GD1a is prevalent) developmental stages. In rat retina the ratio was about 13 and 6 at, respectively, early and late developmental stages. These findings suggest that the prevalence of GD3 and of other "b" pathway gangliosides in adult rat retina neurons could be due in part to the maintenance of a high GD3-/GM2-synthase activity ratio throughout development of the tissue. PMID- 1940916 TI - Classical conditioning-induced changes in low-molecular-weight GTP-binding proteins in rabbit hippocampus. AB - Classical conditioning of Hermissenda, involving paired light-rotation events, results in a 30-35% decrease in the levels of a 20-kDa G protein (cp20). To test whether a similar protein exists in vertebrates, rabbits were trained to associate a tone with periorbital electrical stimulation and G proteins were analyzed by photoaffinity labeling with [alpha-32P]GTP-azidoanilide. A 20-kDa G protein similar to cp20 decreased by 36% in the hippocampus of rabbits subjected to paired tone and electrical stimulation, but not in unpaired controls. Learning specific decreases were also found in the amount of ras protein. PMID- 1940918 TI - The cholinergic regulation of intracellular calcium in the human neuroblastoma, SH-SY5Y. AB - The regulation of intracellular calcium by cholinergic agonists was investigated in the human neuroblastoma SH-SY5Y, loaded with fura-2. The resting free Ca2+ concentration in this cell line was 199 +/- 14 nM (mean +/- SEM, n = 19). At 1 mM extracellular Ca2+, high concentrations of carbachol and acetylcholine evoked a biphasic change in intracellular Ca2+ concentration, consisting of a transient initial peak followed by a decline to a plateau that was significantly higher than the basal level. Carbachol (0.5 mM) and acetylcholine (10 microM) caused a maximal increase in the intracellular Ca2+ concentration, reaching a peak of 465 +/- 52 (mean +/- SEM, n = 12) and 422 +/- 48 nM (mean +/- SEM, n = 7), respectively, in less than 4 s. This initial calcium transient declined to a plateau of 268 +/- 36 and 240 +/- 27 nM for carbachol and acetylcholine, respectively, in approximately 40 s. The plateau persisted until the agonist was displaced by the addition of antagonist. Atropine, hexahydrosiladifenidol (HHSD), pirenzepine, and methoctramine inhibited the carbachol-evoked initial calcium transient with Ki values of 0.85 +/- 0.05, 8.3 +/- 1.6, 411 +/- 36, and 240 +/- 46 nM (mean +/- SEM, n = 3), respectively, and the acetylcholine-induced initial calcium transient with Ki values of 0.48 +/- 0.18, 13.5 +/- 8.5, 192 +/- 32, and 414 +/- 25 nM (mean +/- SEM of two experiments), respectively, results suggesting that an M3 muscarinic receptor was predominantly mediating these effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940917 TI - Dopaminergic neurotoxicity in vivo and inhibition of mitochondrial respiration in vitro by possible endogenous pyridinium-like substances. AB - Elucidation of the mechanism(s) by which 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+) cause parkinsonism in humans and other primates has prompted consideration of possible endogenous MPTP/MPP(+)-like neurotoxins in the etiology of idiopathic Parkinson's disease. Here we examined inhibition of mitochondrial respiration in vitro and neurotoxicity in rats in vivo produced by beta-carbolinium compounds that are presumed to form following Pictet-Spengler cyclization of serotonin. We also evaluated N-methylisoquinolinium, a putative endogenous neurotoxin, in the same manner. The latter compound exhibited MPP(+)-like mitochondrial respiratory inhibition, whereas the beta-carbolinium compounds, although more potent inhibitors of electron transport, exhibited weak accumulation-dependent enhancement of inhibition in intact mitochondria. It is interesting that the beta carbolinium compounds inhibited succinate- as well as glutamate-supported respiration, and are best described as inhibitor-uncouplers. The results of partitioning experiments suggest that both the low accumulation potential and the inhibition of succinate respiration may be a consequence of the beta-carboliniums being in equilibrium with neutral "anhydro" bases. Relative to MPP+, all compounds tested had weak dopaminergic uptake activity in vitro and weak dopaminergic toxicity in vivo, consistent with other findings of relatively low neurotoxic potential for presumed endogenous pyridiniums. PMID- 1940919 TI - Intranigral iron injection induces behavioral and biochemical "parkinsonism" in rats. AB - Elevated iron concentrations in the substantia nigra (SN) pars compacta have been implicated in the development of idiopathic Parkinson's disease. Because, as a transitional metal, iron promotes free radical formation, the role of iron in the degeneration of the nigrostriatal dopamine neurons in Parkinson's disease has received much attention. This study further investigates the cytotoxic effects of iron in the SN. Various concentrations of FeCl3 (1, 5, and 50 micrograms of Fe3+ in 5 microliters) were unilaterally injected into the SN of adult rats. The two lower doses of iron had no effect on striatal dopamine levels or on the behavioral responses of the rats. However, injection of 50 micrograms of Fe3+ resulted in a substantial selective decrease of striatal dopamine (95%), 3,4 dihydroxyphenylacetic acid (82%), and homovanillic acid (45%), without any change in norepinephrine concentration. Dopamine-related behavioral responses, such as spontaneous movements in a novel space and rearing, were significantly impaired, whereas amphetamine administration induced ipsilateral rotation in the iron treated rats. The present study indicates that the nigrostriatal dopamine neurons are susceptible to the presence of ionic iron and thus supports the assumption that iron initiates dopaminergic neurodegeneration in Parkinson's disease. PMID- 1940920 TI - A one-step procedure for isolation of poly(A)+ mRNA from isolated brain capillaries and endothelial cells in culture. AB - The study of the regulation of low-abundance blood-brain barrier (BBB) transcripts either in isolated brain microvessels or in endothelial cells in tissue culture (ECL cells) requires isolation of poly(A)+ mRNA. Therefore, we describe here a single-step method for isolation of poly(A)+ mRNA from brain capillaries or ECL cells using proteinase K/sodium dodecyl sulfate cell lysis and oligo-deoxythymidine cellulose affinity chromatography. The yield of poly(A)+ mRNA was approximately 15-19 micrograms/g of brain or choroid plexus, 14-17 micrograms per batch of isolated capillaries in a single bovine forebrain (190 g), and 6-12 micrograms/10(7) ECL cells. Northern blot analysis showed characteristic and undegraded 2.1- and 1.7-kb actin transcripts in brain capillaries and a 2.1-kb actin mRNA in brain and ECL cells. Northern analysis was also used to quantify the glucose transporter type I transcript, which is very rare in basal ECL cells, and this mRNA was shown to be up-regulated by glucose deprivation. This method represents a significant improvement in the mRNA yield for brain capillaries or cultured endothelial cells compared with the conventional two-step method. PMID- 1940921 TI - Exogenous GM3 ganglioside stimulates process formation and glycoprotein release by cultured bovine oligodendrocytes. AB - Isolated adult bovine oligodendrocytes maintained in vitro for 10 days were treated for 1 day with 50 micrograms/ml of GM3 ganglioside (NeuNac alpha 2-3Gal beta 1-4Glc beta 1-1'ceramide) in serum-free culture medium. The treated oligodendrocytes had significantly longer processes with more branching than control cells in the same medium without GM3. The treatment also stimulated the release of a series of 22-100-kDa, [3H]glucosamine-labeled glycoproteins into the culture medium. Treatment of oligodendrocytes maintained in vitro for 50 days with GM3 for 1 day resulted in a thickening of the processes and the appearance of many fine branches on existing processes as well as a similar stimulation of glycoprotein release into the medium. PMID- 1940922 TI - Methodology for restoring functional leg length in revision total hip arthroplasty. AB - Functional leg length was measured in 30 patients before and after revision total hip arthroplasty. The authors emphasize the importance of preoperative planning, and determination of adjustment of the leg length should be aimed at a balanced attitude of the entire pelvis and lower back. In order to correct the length inequality, the leg was lengthened in the revision in 25 cases, left unchanged in 2 cases, and shortened in 3 cases. The mean functional leg-length inequality was 13 mm before operation and 4 mm after operation. The mean radiographic inequality between the upper surfaces of the iliac crest was 13 mm before operation and 9 mm after operation. The side operated was more often functionally shorter than the other side before operation, and longer than the other side after operation. The authors emphasize the importance of functional leg length in revision hip arthroplasty. The functional length discrepancy can be corrected in revision, but there appears to be a risk of overlengthening. PMID- 1940923 TI - Vitallium-mold arthroplasty of the knee. A case report with 30-year follow-up study. AB - A case was reviewed of a 52-year-old woman who underwent vitallium-mold arthroplasty of the right knee in 1958. After more than 30 years her Hospital for Special Surgery knee score continued to show an excellent rating. The anatomic designed implant, made of cobalt-chrome material and inserted cementless, appears to have withstood the test of time in the knee. PMID- 1940924 TI - Distal femoral plug migration with cement pressurization in revision surgery and a simple technique for its prevention. AB - The notes and radiographs of a consecutive series of 83 hip revisions were studied. In 69 hips, a cemented femoral component was used in which the cement was pressurized and the canal was blocked by an intramedullary plastic plug. It was found that distal migration of this plug occurred very frequently and, in 14 hips (20%), the migration was considered severe. The causes and implications of this are discussed, and a simple technique for preventing the problem is described. PMID- 1940925 TI - Constrained total elbow arthroplasty. AB - In 1972, the senior author designed a condylar-sparing constrained hinge elbow prosthesis with a high-density polyethylene bushing. The condylar-sparing design allows both intercondylar and intramedullary fixation of the humeral component with methylmethacrylate cement. Reattachment of the muscles and collateral ligaments to the preserved condyles provides further stability. The clinical experience spans more than 16 years in 42 elbows with a relatively low loosening rate of 7%. The implant was removed and not replaced in three elbows: one for late infection, one for posttraumatic comminuted fracture of the distal humerus, and one for loosening of a humeral component. A series of 27 patients (31 elbows) with 24-204 months of follow-up study (average, 77 months) had excellent pain relief and an average range of motion of 129 degrees flexion, -44 degrees extension, 69 degrees pronation, and 61 degrees supination. PMID- 1940926 TI - Compressive behavior of human bone-cement composites. AB - Current surgical practice in the implantation of cemented total joint arthroplasties generally creates a zone of variable thickness in which polymethylmethacrylate (PMMA) is intermixed with trabecular bone. The authors' objectives in these experiments were to characterize the compressive mechanical properties of this bone-cement composite material. They found that the mechanical properties of bone-cement composite specimens, fabricated under in vitro conditions that would promote nearly complete cement filling, are closer to the properties of trabecular bone than to those of cement. For both low-viscosity cement (LVC) and PMMA specimens, with the cement introduced by either hand packing or pressurized injection at periods of 2 and 7 minutes, the compressive strengths ranged from 29 MPa to 50 MPa and the compressive moduli from 539 MPa to 1,210 MPa. Cement volume fractions achieved using different filling methods ranged from 76% to 87%. In contrast to previous studies of bone-cement composites using high-density bovine bone, neither mechanical properties nor filling parameters correlated significantly with bone porosity measured prior to filling. The authors expect that the mechanical properties of bone-cement regions created at surgery under less than these ideal in vitro filling conditions will only approach their values as an upper limit. Thus, bone-cement composites created in situ at surgery will also exhibit mechanical properties well below previously assumed values. PMID- 1940927 TI - The metal-backed patella. An invitation for failure? AB - Thirty-one cases of failed metal-backed patellar components requiring revision surgery are reviewed. Two modes of implant failure onset were noted. Within each group, delays in patient presentation and diagnosis of the failed component were encountered. The syndrome of the failed metal-backed patellar component is proposed. The authors conclude that: (1) more of these failures will be seen in the future; (2) this patient population needs appropriate counsel concerning the signs and symptoms of this syndrome as well as more frequent follow-up evaluations; (3) surgeons treating this complication should be prepared to revise all components; and (4) the use of metal-backed patellar components should be discontinued. PMID- 1940928 TI - A relationship between stem orientation and function following total hip arthroplasty. AB - A retrospective gait analysis of patients with cemented Charnley-Mueller total hip arthroplasties was conducted to determine if functional differences exist between patients with femoral stems placed in varus and valgus orientations. Twenty patients and ten normals were studied using gait analysis to quantify joint motion and moments during level walking. In addition, a radiographic analysis of stem placement and mechanics of the reconstructed hip was performed on the total hip patients. All patients selected for the study had excellent clinical results on the basis of a score of 95 or better on the Harris hip rating form. The patients were divided into two subgroupings on the basis of stem orientation. A valgus group was defined as having a valgus stem orientation relative to the femoral shaft, with the femoral head-shaft offset shortened by 5 mm or greater compared to the contralateral unoperated hip, while the varus group was defined on the basis of having a varus stem orientation relative to the femoral shaft, with the femoral head-shaft offset restored to normal or greater than normal. A difference in gait was found between the varus and valgus patient groupings. The varus group had abnormal gait characteristics in the range of hip motion, the flexion-extension moments at the hip, and stride length. The patients in the valgus group had statistically normal gait. The differences in the gait characteristics were interpreted as an attempt to alter forces on the hip joint for patients in the varus group. These alterations were possibly an early indication of a subtle adaptation in patients with varus-placed femoral stems since, historically, a greater percentage of the patients in this configuration, retrospectively, go on to mechanical failures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940930 TI - Effects of hypotensive anesthesia, nonsteroidal antiinflammatory drugs, and polymethylmethacrylate on bleeding in total hip arthroplasty patients. AB - One hundred forty patients ranging in age from 26 to 88 years, who had primary total hip arthroplasty (performed by the same surgeon and lateral surgical approach), were analyzed for intraoperative and postoperative blood loss. The factors affecting blood loss, which include bleeding disorders, medications, duration of surgery, the mean intraoperative blood pressure, and use of cement, were all recorded. A significant reduction in the intraoperative blood loss was observed in the group of patients with hypotensive anesthesia (greater than 20 mmHg drop in the mean intraoperative blood pressure using inhalation anesthetics) compared to the group of patients who did not have hypotensive anesthesia. The patients who had been on aspirin or nonsteroidal antiinflammatory drugs prior to surgery had increased intraoperative and postoperative blood loss compared to the patients who did not take such medications. The effect of cementing with methylmethacrylate on bleeding was also observed; the patients with uncemented implants had a greater blood loss after operation than the patients who had cemented prosthetic components. PMID- 1940929 TI - Evaluation of the painful prosthetic joint. Relative value of bone scan, sedimentation rate, and joint aspiration. AB - Seventy-two joint arthroplasties undergoing total hip or total knee surgery were studied prospectively with plain radiographs, three-phase bone imaging (3PBI), erythrocyte sedimentation rate (ESR), aspiration of the joint for culture, and multiple intraoperative cultures at the time of revision. Intraoperative cultures and the operative appearance were used to form a diagnosis of definite infection (unequivocal microbiology and gross sepsis), possible infection (positive microbiology or gross sepsis), or no infection (neither positive microbiology nor gross sepsis). For the preoperative diagnosis of infection, as opposed to aseptic loosening, 3PBI alone had a sensitivity of 33% and a specificity of 86%. In conjunction with plain radiographs, minimal improvement in accuracy was seen. A preoperative ESR greater than 30 had low sensitivity (60%) and a specificity of (65%). However, the ESR was statistically significantly higher in the joints with definite infection as compared to those joints without infection. The preoperative joint aspiration had a sensitivity of 67% and a specificity of 96% and, therefore, appears to be the most useful single test in the workup of a painful total joint arthroplasty. PMID- 1940931 TI - Effect of patella thickness on patella strain following total knee arthroplasty. AB - Patellar complications following total knee arthroplasty (TKA) have begun to emerge as a major cause of failure. In an effort to understand some of the mechanical factors that might contribute to patellar component failure, a biomechanical study was performed. Quadriceps force and anterior patellar strain were measured during dynamic flexion in 10 fresh, paired human cadaver knee joints. First, tests were performed in the intact knee, followed by either posterior cruciate ligament (PCL) retention or sacrifice of TKA without patellar resurfacing. Tests were then performed following patellar resurfacing with an overly thick, optimum and thin, bony patella. Patellar strain increased in each specimen (with flexion angles of up to 80 degrees), was most pronounced as the bony patella became thinner, was closest to the intact knee when the patella was not resurfaced, and was unaffected by PCL retention or sacrifice. Patellar osteotomy, resulting in a bony patellar thickness of less than 15 mm, resulted in significantly increased strain. TKA systems should include instrumentation that allows precise restoration of overall patellar thickness while maintaining a bony patellar thickness of at least 15 mm. PMID- 1940932 TI - Effect of short-course indomethacin on heterotopic bone formation after uncemented total hip arthroplasty. AB - One hundred consecutive total hip arthroplasties (THA) were allocated into two groups: 92 patients received 25 mg of indomethacin three times daily for 10 days starting on the first postoperative day; 108 patients received no prophylactic treatment. Clinical examination and radiographs were evaluated by an independent observer at 3, 6, 12, and 24 postoperative months. No difference was noted at the bone-prosthesis interface between the two groups. Short-course indomethacin was felt to deter heterotopic bone formation significantly, while having no deleterious effect on stabilization of the St. Michael's madreporic system. Clinical examination and radiographs were evaluated by an independent observer at 3 and 6 postoperative months; all patients have continued to be observed, with an average follow-up period of 2 years following surgery. PMID- 1940933 TI - Evaluation of micromotion in cemented vs uncemented knee arthroplasty in osteoarthrosis and rheumatoid arthritis. Randomized study using roentgen stereophotogrammetric analysis. AB - Twenty-four patients (25 knees) with osteoarthrosis (OA) and 19 patients (20 knees) with rheumatoid arthritis (RA) were operated with bi-tricompartmental knee arthroplasty. The patients were randomized to cemented or cementless fixation of the tibial component. The fixation of the tibial components was examined with roentgen stereophotogrammetric analysis (RSA) up to 24 months after operation. The following parameters representing tibial component micromotion were measured: (1) maximum migration of the prosthetic edge (maximum total point motion, MTPM); (2) distal migration of the prosthetic center (subsidence); (3) maximum proximal movements of the prosthetic edge ("lift-off"); and (4) prosthetic rotations, corresponding to internal/external rotation, adduction/abduction, and forward/backward tilt of the tibial component. All prostheses displayed significant micromotions, which tended to decrease 3-6 months after the operation. The average migration after 2 years, when measured as maximum single axis rotation, and MTPM were about 0.9 degrees-1.5 degrees and 1.0-1.5 mm, respectively, in all four groups. There were no statistically significant differences between cemented and cementless prostheses in either the OA or the RA group. The fixation in the RA patients did not significantly differ from that of the OA patients, perhaps because the RA patients had lower weight and were living a more sedentary life. PMID- 1940934 TI - Revision total knee arthroplasty using the total condylar III prosthesis. AB - Implant selection for the severely damaged knee being treated by revision is difficult. Fixed or rotating hinges have provided mixed results with a high frequency of complication. An alternative to a hinge implant is the total condylar III prosthesis, which can substitute for a deficient collateral ligament. Between August 1980 and April 1987 total condylar III prostheses were used for revision of failed total knee arthroplasties (TKA) of 21 knees in 19 patients. In the same time interval, 649 TKA revisions were performed for a frequency of 3.2% using this prosthesis. The indications for using this prosthesis were bone loss in 10 knees, instability in 9 knees, supracondylar femur fracture in 1 knee, and implant malposition in one knee. At a 4-year follow up evaluation the knee scores were excellent in 25%, good in 25%, fair in 25%, and poor in 25%. Complications occurred in 33% of the knees. The total condylar III prosthesis provided results similar to other constrained implants used for revision in patients with severe bone loss and ligamentous instability. PMID- 1940935 TI - Chronic fatigue syndrome. PMID- 1940936 TI - Glutathione peroxidase in early and advanced Parkinson's disease. AB - A defective antioxidant scavenging system plays a major role in one of the theories of the pathogenesis of Parkinson's disease. The aim of this study was to investigate whether there is a general difference in antioxidant activity between early and advanced cases of Parkinson's disease. Twenty five recently diagnosed patients, without any clinical fluctuations (group A), and 25 patients in a late phase of the disease with severe fluctuations in response to levodopa therapy (group B) were included in the study. Erythrocyte glutathione peroxidase was determined as a measure of antioxidant activity and significantly lower values were found in group B than in group A. Regression analyses in groups A and B showed significant correlation between glutathione peroxidase and duration of disease, but not between glutathione peroxidase and age of patients. PMID- 1940937 TI - Avicenna or Ibn Sina (980-1036 AD). PMID- 1940939 TI - Multiple sclerosis, tropical spastic paraparesis and HTLV-1 infection in Afro Caribbean patients in the United Kingdom. AB - Forty four consecutive patients of Afro-Caribbean origin resident in the United Kingdom (UK) were studied, based on a provisional diagnosis of myelopathy of unknown cause, tropical spastic paraparesis (TSP) or multiple sclerosis (MS). Of 30 patients with progressive paraparesis 27 had serum antibodies to HTLV-1 and were classified as having TSP. Fourteen patients fulfilled the criteria for MS and none of 12 tested had HTLV-1 antibodies. All the TSP patients and nine of those with MS were born in the West Indies. Five of the West Indianborn MS patients had migrated to the UK after adolescence but the duration of residence in the UK before symptoms of MS developed was similar to those born in the UK (average 18 years). The features that differentiated MS from TSP patients, apart from HTLV-1 status, included clinical evidence of cranial nerve involvement, more extensive abnormalities on the brain and cervical cord MRI and asymmetry of the VEP latency increase, all of which were more frequent in the MS group. Of the three patients without a diagnosis one, born in the UK, had marked abnormalities on MRI of the brain indistinguishable from those seen in MS. PMID- 1940938 TI - Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: concerted action guidelines. AB - Serial gadolinium enhanced MRI of the brain detects much clinically silent disease activity in early relapsing-remitting and secondary progressive multiple sclerosis (MS), and thus has an important role in monitoring the effects of therapy. Based on the proceedings of a recent Commission of the European Communities (CEC) workshop and a review of the literature, guidelines are presented for using MRI to monitor treatment trials in MS. The guidelines consider: A) MRI system and techniques; B) patient selection; C) trial design; D) analysis of results. Priorities for future research are also indicated. PMID- 1940940 TI - SEPIVAC: a community-based study of stroke incidence in Umbria, Italy. AB - The SEPIVAC study is a community-based epidemiological survey of incidence and outcome of acute cerebrovascular disease in the Sixth Local Health Unit, Umbria, Italy (population 49,218). The study was carried out from 1 September 1986 to 31 August 1989. There were 375 patients who were registered with a first ever stroke, with a crude rate of 2.54 (95% confidence limits 2.29-2.81) per 1000 per year; the rate adjusted to the European population is 1.55 (CL 1.36-1.77). The age adjusted relative risk for males is 1.35 (CL 1.10-1.66). Up to 15% of the patients were not admitted to hospital during the acute phase of their disease. At least 286 (76.3%, CL 72-80.6) of the cases were due to cerebral ischaemia; in 56 of these (19.6%, CL 15-24.2) a clinical diagnosis of lacunar ischaemia was made. The 30 day case fatality rate was 20.3% (CL 16.2-24.3); between one and six months 7.5% (CL 5-10.6) of patients died. PMID- 1940941 TI - Factors influencing dressing performance after stroke. AB - Sixty consecutive patients with a diagnosis of stroke were assessed using the Nottingham stroke dressing assessment as well as a series of physical and cognitive assessments. Generally the items of clothing worn on the lower half of the body were significantly correlated with the physical assessments and the items of clothing worn on the upper half were significantly correlated with the cognitive assessments. These results support other studies which suggest that motor recovery and perceptual abilities are important determinants of dressing ability. PMID- 1940942 TI - Single small enhancing CT lesions in Indian patients with epilepsy: clinical, radiological and pathological considerations. AB - Thirty consecutive Indian patients with focal or generalised seizures and single, small (less than 10 mm), enhancing lesions on CT scans (SSECTL) were studied. Five patients (Group A) were treated with anticonvulsants alone and did not have a biopsy. In ten patients (Group B) a CT guided stereotaxic biopsy of the lesion was carried out and in the remainder (15-Group C) and excision biopsy of the lesion was carried out following CT guided stereotaxic localisation. In all patients in Group B the lesion were reported as "chronic nonspecific inflammation". In seven of 15 patients in Group C the lesions showed a cysticercus with a granuloma and in a further five the pathology was that of a "parasitic granuloma" but the parasite could not be identified. Biopsy did not reveal a tuberculoma or neoplasm in any of the patients. The lesions studied are the same as "disappearing" CT lesions reported in Indian patients, as in 12 of 15 patients in Groups A and B, who could be followed up for more than three months, the lesions had spontaneously disappeared or left calcific residues. It is concluded that in Indian epileptic patients with SSECTL cysticercosis is the commonest aetiology. A treatment protocol for these patients is suggested on the basis of the findings. PMID- 1940943 TI - Central sleep apnoea in congenital muscular dystrophy. AB - Sleep-disordered breathing may occur in a wide variety of neuromuscular syndromes, and may present with diverse, often isolated, symptoms or findings such as excessive daytime sleepiness, pulmonary hypertension, congestive heart failure, morning headaches, or hypoxia-induced nocturnal seizures. The authors report two sisters with congenital muscular dystrophy in whom central sleep apnoea resulted in the isolated symptom of nocturnal seizures in one, and morning headaches in the other. Review of the literature reveals that sleep-disordered breathing may be common in neuromuscular disorders, and may often be present when clinical weakness is mild, and insufficient to result in diurnal respiratory dysfunction. PMID- 1940944 TI - The relationship between trauma and idiopathic torsion dystonia. AB - Generalised, multifocal or segmental idiopathic torsion dystonia (ITD), is caused by an autosomal dominant gene with reduced penetrance in about 85% of cases. Of 104 patients with these types of ITD, 17 (16.4%) gave a history which suggested that dystonic movements had been precipitated or exacerbated by trauma. Eight of these 17 patients had affected relatives. If precipitated, dystonia appeared first in the injured part of the body within days or up to 12 months after the trauma and later became more widespread. Peripheral injuries may influence basal ganglia function and provoke the onset of dystonic movements in individuals who are ITD gene carriers. PMID- 1940945 TI - Treating organic abulia with bromocriptine and lisuride: four case studies. AB - Abulia refers to an impairment of will, or the inability to initiate behaviour and action. There are reports of successful treatment of akinetic mutism, the most severe form of abulia, with bromocriptine. Four case studies are presented describing the successful treatment of abulia at a lesser severity than akinetic mutism with bromocriptine. Abulia was caused by brain damage due to alcohol in two cases, Wilson's disease and basal ganglia infarct in one each. Maximum bromocriptine dose varied from 25-70 mg. All improved considerably. Withdrawal or reduction of medication in three produced deterioration. The prescription of a neuroleptic drug had a similar effect in the fourth. One patient with a previous history developed a depressive relapse and so the drug was withdrawn and lisuride introduced. This produced a similar improvement. These cases highlight the value of identifying the syndrome of organic abulia and suggest that dopamine agonists may have a place in its treatment, though controlled studies are needed. PMID- 1940946 TI - Platinum-based chemotherapy for recurrent CNS tumours in young patients. AB - Twenty nine patients (median age 12 years) with a CNS tumour, received platinum based chemotherapy for assessable disease. In 23 patients there was an objective response with improvement lasting for a median duration of 11 months. There was little difference in the response to cisplatinum or carboplatin therapy. The response rates in specific disease groups were: medulloblastoma 8/10, two with a complete response (CR) and six with a partial response (PR); ependymoma 1/5 PR; pineal retinoblastoma 5/5 with three CR and two PR; primitive neurectodermal tumours (PNET) 2/2 PR and pineal germ cell tumours 6/6 with four CR and two PR. It is concluded that platinum-based chemotherapy has a beneficial effect on CNS tumours of the CNS, especially medulloblastoma, ectopic intracranial retino blastoma and pineal germ cell tumours. PMID- 1940948 TI - Monosporium apiospermum meningoencephalitis: a clinico-pathological case. AB - Twenty nine cases of central nervous system infection due to Monosporium apiospermum have been reported. Six of them occurred after an aspiration pneumonia following a near drowning. The case of a 53 year old man is reported: M apiospermum was isolated from cerebrospinal fluid, sputum, urine and from the mud of the ditch where the patient had fallen. Though the treatment used recommended doses of intravenous, intrathecal and intraventricular amphotericin B, it was ineffective and the patient died 97 days after the near drowning. Necropsy showed that the ventricular infectious process was more prominent distant from the antifungal ventricular source. PMID- 1940949 TI - The muscle findings in the neuroleptic malignant syndrome associated with lysergic acid diethylamide. AB - A detailed pathological description of the muscle findings in a case of the neuroleptic malignant syndrome (NMS) following ingestion of lysergic acid diethylamide (LSD) is given, including the first ultrastructural analysis. Focal necrosis, oedema, and hypercontraction of fibres with glycogen and lipid depletion, were identified, all of which had resolved completely a year later. The findings are compared with those in malignant hyperthermia. It is suggested that the results support the view that in NMS, the muscle rigidity is due to central mechanisms and, in both this disorder and malignant hyperthermia, it is responsible for the hyperpyrexia and its life-threatening complications. PMID- 1940947 TI - The influence of food on postural hypotension in three groups with chronic autonomic failure--clinical and therapeutic implications. AB - The effect of a balanced liquid meal on supine and postural blood pressure (BP) responses was investigated in three groups of patients with chronic autonomic failure; 10 with associated neurological impairment (multiple system atrophy (MSA), Shy-Drager syndrome) and seven without (of which five had pure autonomic failure (PAF); and two had a deficiency of the enzyme dopamine beta hydroxylase, DBH-deficiency). All had marked postural hypotension. Subjects with normal autonomic function were also studied. In MSA and PAF food lowered supine BP substantially, with a more rapid and greater fall in PAF. After food, the levels of BP reached were considerably lower because of the reduced supine BP and many had to be returned to the horizontal position earlier than before. Ingestion of a similar volume of water alone had no effect in MSA or PAF. In DBH deficiency, food had variable but minimal effects on BP while supine and during head-up tilt. In subjects with normal autonomic function food did not affect BP. The BP responses to food thus varied in the three groups with chronic autonomic failure. The influence of food on both supine and postural BP therefore should be considered in the clinical and laboratory assessment of autonomic dysfunction and in relation to therapeutic approaches, designed to alleviate postural hypotension. PMID- 1940950 TI - Migraine coma. PMID- 1940951 TI - Lamellated sensory corpuscles within the endoneurium. PMID- 1940952 TI - Permanent oculomotor palsy with occlusion of the internal carotid artery. PMID- 1940953 TI - Penicillamine treatment of Wilson's disease and optic neuropathy. PMID- 1940954 TI - Serum erythropoietin levels in von Hippel-Lindau syndrome. PMID- 1940955 TI - Application of gadolinium-DTPA magnetic resonance imaging for detection of a filum terminale myxopapillary ependymoma allowing successful surgical resection. PMID- 1940956 TI - Plasma dopamine-beta-hydroxylase activity in depressed patients: role of treatment. PMID- 1940958 TI - Complications of carotid angiography. PMID- 1940957 TI - Asymmetrical "temporal" Pick's disease? PMID- 1940959 TI - Diaphragmatic weakness in hereditary motor and sensory neuropathy. PMID- 1940960 TI - Effects of CDP-choline on the recovery of patients with head injury. AB - A single blind randomized study has been conducted in 216 patients with severe or moderate head injury, with the aim of comparing the evolution of those that received only conventional treatment with the evolution of those treated with CDP choline. Our results indicate that CDP-choline improves the global outcome of patients. We have found a trend towards a greater improvement in motor, cognitive and psychic alterations in the patients treated with CDP-choline, as well as a shortening of the stay in the hospital ward in the patients receiving this drug that initially presented with severe head injuries. PMID- 1940961 TI - Biochemical rationale for the use of CDPcholine in traumatic brain injury: pharmacokinetics of the orally administered drug. AB - A pharmacokinetic analysis of CDPcholine has been carried out treating either rats or dogs by oral administration with the double labelled molecule. [methyl 14C,5-3H]CDPcholine represents a useful tool to test the structural integrity of this compound during the transmembrane transport and to follow the metabolic fate of cytidine and choline fragments. Furthermore, the identification of the labelled metabolites of the exogenously administered CDPcholine in the various organs allows us to draw inferences about its pharmacological mechanism(s). These studies appear of great interest in view of the extensive therapeutic use of the molecule in the treatment of several CNS pathologies including traumatic brain injury. The results of this work can be summarized as follows. (a) The molecule is rapidly cleaved at the level of the pyrophosphate bridge and a fast uptake of the hydrolytic products occurs. (b) The metabolism of the molecule is characterized by a differential utilization of the two moieties by the various organs. Liver is the most active organ in utilizing CDPcholine with a preferential uptake of the choline fragment. (c) The [3H]cytidine moiety, in all the organs examined, appears to be incorporated into the nucleic acid fraction via the cytidine nucleotide pool. The [14C]choline moiety is in part converted into betaine, which in turn acts as methyl donor to homocysteine, yielding [14C]methionine, subsequently incorporated into proteins. The time-dependent increase in the labelling of phospholipids is indicative of a recycling of choline methyl groups via CDPcholine and/or S-adenosylmethionine. (d) The uptake of CDPcholine by the brain is relatively low; however, a good metabolic utilization of the drug can be observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1940962 TI - Head injuries: incidence and outcome. PMID- 1940963 TI - Traumatic brain injuries: structural changes. AB - A host of complications and consequences may follow a contusion or other brain injury of any sort. An appreciation of the temporal evolution of the contusion from a microscopic standpoint is useful to a full understanding of the process by which physical force damages the brain and how the brain reacts to this damage. Some disruptions of the blood brain barrier quite early will result in extracellular edema. The microscopic appearance of an edematous area is usually spongy with numerous vacuoles. The neuropil may appear bubbly, and glial cells may be swollen. If edema has been long standing, the vacuoles may be larger and in fact a small cyst may appear in the white matter. If focal cerebral edema is not present for long periods of time and the underlying cause has been corrected, residual fluid and electrolytes are eventually removed, restoring the neuropil to a normal state, leaving no sign of its presence. However, in longer standing lesions, myelin pallor and some reactive gliosis may remain indefinitely. Neurons may show swelling very early and for a short period of time, which gives way to shrinkage, eosinophilia, and nuclear pyknosis. These changes may be observed at the periphery of lesions for as long as 5 or 6 months after the initial event. Before dissolution, nuclear pyknosis may remain in the tissue for many days and possibly longer, and may even become mineralized in situ (ferruginated neurons) to remain for years. In a traumatic lesion, swollen and ballooned axons may be found in and around the contusion but also at great distances from it (diffuse axonal injury). Axonal ballooning may be observed between 24 and 48 h postinjury and may persist wherever found for many years. Selective axonal calcification has been observed in humans as well as in experimental trauma. At about 7-10 days postinjury increased numbers of astroglia probably are present. Over the ensuing weeks and months, and probably years, astrocytes increase in number and in fibrillary appearance, eventually resulting in a glial scar in and about the injured area. It is thought that this reactive gliosis results in restoration of the blood-brain barrier in the damaged area. PMID- 1940964 TI - Changing patterns in acute management of head injury. PMID- 1940965 TI - Treatment of postconcussional symptoms with CDP-choline. AB - To evaluate the efficacy of cytidine diphosphoryl choline (CDP-choline) in treating postconcussional symptoms for one month after mild to moderate closed head injury (CHI), we completed a preliminary double blind placebo-controlled study. Fourteen young men admitted to the neurosurgery service after sustaining mild to moderate CHI were randomized to oral CDP-choline (1 g) and placebo control groups which were matched for age, education and severity of impaired consciousness. Baseline (prior to discharge) and one month examinations consisted of a structured postconcussional symptom interview and neuropsychological tests. Results (Wilcoxon test) showed that CDP-choline produced a greater reduction of postconcussional symptoms than placebo (P less than 0.005). Analysis of the neuropsychological findings revealed a significantly greater improvement in recognition memory for designs in the CDP-choline treated patients (P less than 0.02) whereas other changes in test performance did not differ for the two groups. Pending replication in a larger series of patients, our findings suggest that CDP-choline may be effective in treating sequelae of mild to moderate CHI. PMID- 1940966 TI - CDP-choline in the treatment of cranio-encephalic traumata. PMID- 1940967 TI - Ways to facilitate rehabilitation in neurotraumatology. PMID- 1940968 TI - Cardiovascular autonomic function in multiple sclerosis. AB - In this study blood pressure (BP) and heart rate (HR) responses to standing and HR responses to deep breathing were assessed in 34 patients with clinically definite multiple sclerosis (MS) and 63 healthy subjects. Normal ranges, which were clearly age related for both HR responses, were obtained. The BP response to standing was abnormal in 13% of the MS patients, these patients demonstrating significant postural hypotension. The HR response to standing was abnormal in 28% of the MS patients, with a normal initial increase in heart rate and a significantly reduced reflex bradycardia. On deep breathing 36% of MS patients showed abnormal HR changes. The resting HR did not differ between both groups. Abnormalities of one or more tests were found in 53% of the MS patients. No relationship was found between abnormal cardiovascular autonomic responses and the symptoms, duration, severity and progression of the disease. Based on clinical and magnetic resonance imaging findings no indications were found for localisation of the autonomic disturbances in the brainstem. It is suggested that at least a part of the cardiovascular autonomic lesions in MS is located outside the brainstem, i.e. in supramedullary reflex pathways or in the spinal cord. PMID- 1940970 TI - Clinical signs in severe Guillain-Barre syndrome: analysis of 63 patients. AB - Clinical data are presented of 63 artificially ventilated Guillain-Barre patients. About half of them had an antecedent event. In 57% the disease was heralded by sensory symptoms. The mean progressive phase lasted 12 days, the plateau 12 days and the recovery phase 568 days. In all patients one or more cranial nerves were involved, most often leading to facial palsy or difficulties in swallowing. Three-quarters of the patients had sensory signs, proprioceptive more often than superficial. Autonomic disturbances were common, especially hypertension and tachycardia. Twenty-two percent of the patients were severely confused in the first weeks of the disease. Laboratory examination showed atypical lymphocytes in the blood of 37% of patients and disturbed hepatic function tests in 79%. CSF protein level was elevated in all patients, with a mean value of 1.5 g/l. PMID- 1940969 TI - PET studies of cortical diaschisis in patients with motor hemi-neglect. AB - Six patients presenting with multimodal, predominantly motor hemi-neglect, were investigated by 15O2 or 18F-DG and PET to study the local cerebral metabolism in intact regions. All had suffered from an acute right-sided (n = 5) or left-sided (n = 1) focal hemispheric lesion (cortico-subcortical and purely subcortical in three patients each). Frontal and parietal cortices on the side of the lesion were significantly hypometabolic relative to the other side in each case, presumably as a result of diaschisis, whereas thalamic hypometabolism was significant in only 4 patients. Compared to absolute metabolic rates for controls, the uninjured hemisphere showed a trend towards hypometabolism. Hence, true hyperactivity of the contralateral hemisphere with respect to the ipsilateral cerebral cortex was not associated with motor hemineglect in this series. On the contrary, hemineglect was associated with a widespread hypometabolism of the entire ipsilateral cerebral cortex in the context of a moderately reduced metabolism of the ipsilateral thalamus and contralateral cerebral cortex. These findings are consistent with the implication of a cortico subcortical network serving attention. PMID- 1940971 TI - Residual signs in severe Guillain-Barre syndrome: analysis of 57 patients. AB - The residual signs in a group of seriously paralyzed Guillain-Barre patients are reported (follow-up 2-24 years) and the social effects of the illness are discussed. Thirty-five percent of the patients had recovered completely at the time of the follow-up examination, 35% had minimal residual motor signs and 30% had a moderate or severe residual paresis. The most serious residua were found distally in the legs. Muscles innervated by nerves running along an entrapment site had the most severe deficits. Sensory signs were present in 49% of the patients. More than half of the patients considered themselves to be cured. The others were more or less handicapped by their sequelae. Of the adults, 60% resumed work, 25% found a less demanding job and 15% did not return to work. Statistically significant correlations were found between the degree of residual motor deficit and the severity of the weakness in the acute phase, the duration of the plateau phase or the duration of the artificial ventilation. PMID- 1940972 TI - Nuclear magnetic resonance T2 relaxation times in multiple sclerosis. AB - An original method was used to carry out the mathematical analysis of T2 transverse magnetization decay curves and the measure of T2 relaxation times on multiple sclerosis (MS) patients. The presumably normal white matter (WM) of these patients presented higher T2 relaxation times (98.6 msec), in comparison with that found in a population sample (88 msec). In this case, magnetization decay curves remain mostly monoexponential and are characterized by a single T2. On the other hand, areas of increased signal (AIS) curves are always better fitted by a biexponential function characterized by a short (82 msec) and a long (greater than 200 msec) T2. The spreading out of long T2 varies from one AIS to another in the same patient and among different patients; values of long T2 also vary with time, but without any correlation with the clinical state. In fact, no correlation was been established between relaxation times and clinical parameters. Quantitative MRI therefore enables a different approach to interpret MRI images; results suggest that several histobiochemical parameters play a role in the pathogenesis of an AIS and that MS is a dynamic and constantly evolving disease. PMID- 1940973 TI - Muscle regeneration after imposed injury is better in younger than older mdx dystrophic mice. AB - The ability of a fast-twitch dystrophic muscle to regenerate was compared at two ages to control muscle regeneration. Myofiber growth, and the distribution of nuclei in fibers were used to characterize the muscle regeneration 3 and 6 weeks after injury. In control and mdx muscles, myosatellite cell proliferation was completed by 3 weeks after injury. Mdx muscle regenerated as well as controls, based on similar distribution of myofiber cross sectional area, and the percent of centronucleation, typical of regenerated fibers. In addition, muscle from the younger dystrophic mdx mice grew to unoperated levels with no net change in fiber area distribution, while older muscles did not regenerate as well. There were also more peripheral (satellite cell) nuclei observed in younger mdx muscle than in older muscles, after the most active phase of dystrophy. PMID- 1940974 TI - Autoantibodies to GM1 ganglioside: different reactivity to GM1-liposomes in amyotrophic lateral sclerosis and lower motor neuron disorders. AB - We studied the ability of anti-GM1 ganglioside antibodies to bind to GM1 in a lipid, "membrane-like" environment. Liposomes containing GM1 were synthesized to simulate this environment. We then compared the binding of anti-GM1 a autoantibodies to GM-1-liposomes and to purified GM1. Antibody binding was quantitated using enzyme-linked immunosorbent assay methodology. Our results showed a 250-fold variation in the ability of anti-GM1 antibodies to bind to GM1 liposomes. There was no correlation between GM-1-liposome binding and the carbohydrate specificities of the anti-GM1 antibodies. However, anti-GM1 antibodies from patients with amyotrophic lateral sclerosis (ALS) showed a 4 fold greater binding to GM1-liposomes than antibodies from patients with lower motor neuron (LMN) syndromes. We conclude that a lipid, presumably "membrane-like", environment may greatly influence the degree of anti-GM1 antibody binding to GM1. The low levels of anti-GM1 antibody binding to GM1-liposomes in patients with LMN syndromes may provide a diagnostic means for distinguishing these patients from those with ALS. Anti-GM1 antibodies from patients with ALS may bind especially well to neuronal membranes containing GM1 in vivo. PMID- 1940975 TI - Comparative analysis of cytokine patterns in immunological, infectious, and oncological neurological disorders. AB - Interleukins (IL) 1, 2, 4, 6 and soluble IL-2 receptor (sIL-2R), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were measured in CSF and serum from patients with relapsing-remitting and chronic multiple sclerosis, Guillain-Barre syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, HIV infection, bacterial meningitis, viral encephalitis, meningeal carcinomatosis, hematologic meningeal malignancies, and disseminated melanoma. Our findings suggest that monitoring of disease activity in neuroimmunologic disorders by means of IL-1 beta, IL-2, sIL-2R, or IL-4 determination will not prove useful. IL-6, on the other hand, indicates relapse in multiple sclerosis and active disease in Guillain-Barre syndrome and meningeal carcinomatosis. High CSF TNF-alpha in metastatic melanoma and frequent detection in CSF of the multifunctional B-cell growth factor, IL-6 (27/30) and oligoclonal immunoglobulin bands (33%) in meningeal carcinomatosis confirm an intrathecal immune response in disseminated leptomeningeal neoplasia which might be amenable to therapeutic immunomodulation. PMID- 1940976 TI - Noradrenergic nerve fibers of the rectal mucosa in autonomic disorders: comparison of histochemical study with clinical severity and changes in plasma noradrenaline induced by standing. AB - A histochemical study was carried out on the rectal mucosae biopsied from 20 patients with autonomic dysfunctions and 13 controls using a catecholamine fluorescent staining method, and the rectal noradrenergic nerve fiber lesions were compared with the severity of autonomic symptoms and disturbance of plasma noradrenaline increase in response to standing in 17 patients. In 9 patients with type I familial amyloid polyneuropathy and 1 with acute pandysautonomia, the number of fluorescent nerve fibers was greatly reduced, and the degree of depletion correlated well with the other 2 parameters showing the severity of autonomic dysfunction. In contrast, rectal noradrenergic nerve fibers were normally preserved in 10 patients with multiple system atrophy, although they suffered from severe autonomic symptoms with poor noradrenaline response to the postural loading. It is concluded that noradrenergic nerve fiber lesions in the biopsied rectal mucosa may represent the systemic involvement of sympathetic post ganglionic nerves. PMID- 1940978 TI - MAP5 in cultured hippocampal neurons: expression diminishes with time and growth cones are not immunostained. AB - A monoclonal antibody was used to determine both the expression of the microtubule-associated protein MAP5 in cultured foetal rat hippocampal neurons as a function of culture age and the cellular distribution of the protein. When cultures at days 2 and 3 were examined by fluorescence microscopy, MAP5 immunostaining was localized intensely in neuronal cell bodies and neurites but not in growth cones. Extensive labelling of axons was seen at days 4 and 5. MAP5 staining was still prominent in neurons after 16 days in culture, and neurites at this time had grown over astrocytes but had completely avoided islands of non astrocytic cells. MAP5 immunostaining was almost undetectable in cells that had been in culture for 20 days. The decreasing expression of MAP5 in cultured neurons as a function of time parallels that previously shown for MAP5 in intact neonatal rat brain. The effect of elevated temperature on MAP5 expression was also examined. Neurons grown for 9 days at 40 degrees C showed the same cellular distribution of MAP5 as cells grown at 37 degrees C. In particular, growth cones were again negative for MAP5 immunostaining. The absence of MAP5 in growth cones appears consistent with the fact that these structures contain labile microtubules. MAP5 has been shown to be a component of microtubule crossbridges and its absence might thus be expected to contribute to microtubule lability. PMID- 1940977 TI - Tumor necrosis factor and interleukin-1 in the CSF and sera of patients with multiple sclerosis. AB - Serum and cerebrospinal fluid (CSF) from 31 patients with multiple sclerosis (MS) were examined to determine the levels of tumor necrosis factor (TNF) and interleukin (IL)-1 alpha (or IL-1 beta) by an enzyme-linked immunosorbent assay. TNF was detected in 29 (93.5%) of CSF from 31 cases of MS. TNF was also detectable in 100% of CSF from patients with acute relapsing MS in exacerbation. Patients with acute relapsing MS in exacerbation showed significantly higher CSF levels of TNF as compared with either those in remission or the controls (P less than 0.001 and P less than 0.0001, respectively). Increased levels of TNF were also detected in 35.5% of the MS sera, and especially in those with acute relapsing MS in exacerbation. Increased TNF levels were also frequent in the CSF and sera of patients with Guillain-Barre syndrome (GBS), which is also a demyelinating disease. No IL-1 alpha (or IL-1 beta) was detected in either CSF or sera of 31 MS patients. It is considered likely that TNF CSF levels may reflect disease activity in MS. PMID- 1940979 TI - Concomitant salicylate-induced alterations of outer hair cell subsurface cisternae and electromotility. AB - Isolated cochlear outer hair cells undergo rapid, force-generating length changes in response to electrical stimulation. The cellular mechanism responsible for electromotility and its structural substrate is not yet known. Salicylates reduce and block electromotility in vitro. Therefore, we exposed isolated outer hair cells from the guinea pig cochlea to various doses of sodium salicylate and evaluated both ultrastructural changes and responses to electrical stimulation. Following salicylate superfusion, the subsurface cisternae showed dilatation, vesiculation and a deviation from their normal, unfenestrated, axial orientation below the plasma membrane. These changes were time and dose dependent and reversible over a time course of about 30 min. Electromotility was blocked and showed recovery following the same time course as the salicylate-induced reversible structural changes. These results indicate that intact, unfenestrated subsurface cisternae are required for the optimal generation of electrically induced motility in mammalian outer hair cells. PMID- 1940981 TI - Distribution of parvalbumin immunoreactivity in the human brain. AB - The cellular distribution of parvalbumin-like immunoreactivity (PA-LI) in the human brain was investigated by peroxidase-antiperoxidase methods using antiserum to rat skeletal muscle parvalbumin. PA-LI was present in non-pyramidal neurons of the cerebral cortices, stellate cells, basket cells and Purkinje cells in cerebellar cortices, and neurons of some nuclei in human brain stem; the distribution of PA-LI in human brain was very similar to that in rat brain. These results indicate that PA-LI is widely distributed in a specific subpopulation of neurons of the human brain. PMID- 1940980 TI - Pharmacokinetics of total and free valproic acid during monotherapy in infants. AB - The pharmacokinetics of free and total valproic acid (VPA) in plasma and whole blood after oral administration during steady state was investigated in seven infants (mean age 10.7 months) receiving monotherapy. The VPA concentrations in whole blood closely followed those in plasma but at a reduced level. A positive correlation was found between dose and mean plasma concentration (r = 0.71). Mean terminal half-lives were similar in plasma and whole blood (12.5 and 15.5 h, respectively), but were considerably longer than for free VPA (6.4 and 6.5 h, respectively; P less than 0.01). There was a significant decrease in half-lives with increasing age (P less than 0.05). Plasma and whole blood clearance for total VPA was higher than reported in older infants and adults (17.8 and 28.9 ml/kg per hour) and was considerably higher for free VPA (127.6 and 188.8 ml/kg per hour, respectively). The increase in clearance compared with that in older subjects is well in concordance with a lower protein binding of VPA (mean 85.3%). Of special importance is that the percentage of unbound VPA increased with increasing concentrations of total VPA. The fraction of unbound VPA in plasma increased even more in subjects with low albumin concentrations (P less than 0.01). PMID- 1940982 TI - Myoglobinuria and carnitine palmityl transferase deficiency in father and son. AB - A 18-year-old man had recurrent myoglobinuria following exercise and fasting. His parents originated from the same village, which has less than 1000 inhabitants. His 53-year-old father suffered from similar episodes, whereas his mother and elder brother were symptom free. Biochemical investigations on muscle and platelets disclosed carnitine palmityl transferase (CPT) deficiency in the patient and his father. His mother and brother showed intermediate CPT values consistent with their being heterozygotes. This appears to be the first report of CPT deficiency with recurrent myoglobinuria in two generations (so-called quasidominant transmission). PMID- 1940983 TI - Complement allotypes in familial and sporadic Alzheimer's disease. AB - To resolve conflicting findings on the association of complement allotypes with Alzheimer's disease (AD) we have studied the C4 phenotypes in 33 sporadic cases and in one family with familial AD. We found no association with complement alleles in familial or sporadic AD, even though a familial case had absence of the C4 null allele (C4BQ0). Our data do not suggest a role for complement genes in the pathogenesis of AD. It also seems that the C4B2 allele cannot be used as a marker for AD as has been suggested by others. PMID- 1940984 TI - Wilson's disease: normalisation of cortically evoked motor responses with treatment. AB - A newly diagnosed patient with Wilson's disease is reported in whom the only clearly pathological neurophysiological findings before treatment were abnormal electromyographic (EMG) responses evoked by transcranial magnetic brain stimulation. Serial examinations over 10 months following commencement of treatment with D-penicillamine revealed normalisation of EMG responses. Pathophysiologically, the initially abnormal EMG responses probably resulted from reversible impairment of impulse propagation along cortico-motor-neuronal pathways and/or a reduced excitability of cortical cells due to impaired function of the basal ganglia. PMID- 1940986 TI - A case of unilateral opercular syndrome associated with a subcortical lesion. AB - A patient who developed a unilateral opercular syndrome following a cerebrovascular accident is described. Computed tomography showed that the lesion did not affect the opercular cortex, but involved deep white matter and the head of the caudate nucleus of the left hemisphere. Persistent hypophonia and transient aphasia were associated. Comparison with previous cases is discussed. PMID- 1940985 TI - Immunoglobulin G subclass preference of intrathecally produced HIV-specific oligoclonal antibodies. AB - Cerebrospinal fluid (CSF) and serum samples from 16 HIV-seropositive subjects were examined by ELISA and isoelectric focusing for the presence of HIV-specific immunoglobulin G (IgG) subclass antibodies. Autochthonous synthesis of IgG in the CSF was demonstrated in 11 patients. Intrathecally synthesized antibodies specific for individual HIV structural proteins were largely restricted to IgG1 (10 of 11 patients). One patient revealed additional local synthesis of IgG2 antibodies related to HIV-p15. In another patient locally produced antibodies specific for HIV consisted entirely of IgG4. In this patient amounts of locally produced antibodies were too low to be detected by routine procedures (calculation from an evaluation graph). No local synthesis of HIV-related IgG3 was demonstrated in any patient. Further studies will be needed to show whether determination of IgG-subclass-restricted antibodies to HIV is of prognostic value. PMID- 1940988 TI - A case of progressive supranuclear palsy with widespread senile plaques. AB - A case of progressive supranuclear palsy (PSP) with frontal lobe atrophy is reported, in which many senile plaques were widely distributed in the neocortex, the entorhinal cortex, the amygdala, and, to a lesser extent, the cerebellar cortex, but not in the hippocampus. Most of the plaques were of the diffuse and primitive types. They were well visualized by beta-protein immunostaining, modified Bielschowsky staining and methenamine silver staining, but were not seen by Bodian staining. The widespread distribution of senile plaques in the cerebral and cerebellar cortices was far beyond that seen in normal aging, and was reminiscent of concomitant Alzheimer's disease (AD). Unlike AD, however, this case had neither senile changes in the hippocampus nor neurofibrillary tangles in the amygdala and entorhinal cortex. It seems that many senile plaques may appear widely in the cerebral cortex and even, to a lesser extent, in the cerebellar cortex of some patients with PSP. Additional case studies using sensitive silver and amyloid antibody preparations are required to elucidate the presence of senile plaques in the cerebral cortex of PSP. PMID- 1940987 TI - MRI in tuberculous meningoencephalitis: report of four cases and review of the neuroimaging literature. AB - The contribution of MRI is reported in four adult patients with tuberculous meningoencephalitis (TbM) and with autopsy correlation in one. Contrast-enhanced T1-weighted MRI revealed the characteristic basal meningeal inflammation of TbM and its focal spreading into adjacent brain. Mixed and T2-weighted pulse sequences delineated a plethora of parenchymal abnormalities. Their relation to TbM was established by a close matching of the patient's neurological findings, contrast enhancement or a change in lesion size. The latter accurately reflected the clinical course in all patients. It remained difficult, however, to distinguish between ischaemic and inflammatory changes, which in some locations were intermixed even histologically. From our experience and that of other groups, MRI provides more diagnostic information in TbM than CT. Moreover, MRI promises to be a useful tool for monitoring treatment response. PMID- 1940989 TI - Reversal of severe neurological abnormalities after vitamin B12 replacement in the Imerslund-Grasbeck syndrome. AB - Vitamin B12 malabsorption in the ileum has been postulated as the underlying cause of the Imerslund-Grasbeck syndrome comprising megaloblastic anemia, proteinuria, and multiple neurological abnormalities. A young Saudi child with spasticity, truncal ataxia, cerebral atrophy, megaloblastic anaemia and proteinuria is described. Replacement therapy with parenteral vitamin B12 resulted in the complete resolution of his neurological findings and brain atrophy. PMID- 1940991 TI - Pseudotumour cerebri and carpal tunnel syndrome associated with danazol therapy. PMID- 1940990 TI - Korsakoff's syndrome as the initial presentation of multiple sclerosis. AB - A 37-year-old man presented with an acute amnestic syndrome of Korsakoff's type and an upper brain-stem oculomotor syndrome. After a moderate improvement with steroid therapy, he developed progressive behavioural changes due to a frontal lobe syndrome, in addition to motor and visual impairment. Memory performance was investigated on several occasions during an 11-year follow-up. Diagnosis of laboratory-supported definite multiple sclerosis was established and magnetic resonance imaging showed disseminated white matter lesions, especially in both medial temporal lobes. No other cause than multiple sclerosis was found for the amnestic syndrome. Among the rare cases of Korsakoff's syndrome in the course of multiple sclerosis, this is to our knowledge the first case in which a memory deficit was the initial manifestation of the disease. PMID- 1940992 TI - Acute ataxia coincident with seroconversion for anti-HIV. PMID- 1940993 TI - The incidence of thoracic vertebral fractures in a Japanese population, Hiroshima and Nagasaki, 1958-86. AB - The incidence of thoracic vertebral fractures (TVF) in a Japanese population of 14,607 individuals from Hiroshima and Nagasaki was determined by sex, age, birth cohort, and exposure to atomic bomb radiation. The diagnosis of TVF was based on lateral chest radiographs made from 1 July 1958 to 28 February 1986. The subjects, who were born between 1880 through 1939, were categorized by sex into 10-year birth cohorts. TVF incidence increased by a factor of 1.7 in all birth cohorts with each 10-year increase in age in females, but did not increase with age in males. The incidence was significantly lower in the younger birth cohorts in both sexes. The incidence declined by a factor of 0.5 in males and 0.6 in females for each 10-year decrease in the year of birth. TVF incidence did not differ between the cities, and no correlation with atomic bomb radiation exposure was demonstrated. PMID- 1940994 TI - An application of longitudinal methods to the analysis of menstrual diary data. AB - Despite the considerable morbidity associated with menstrual dysfunction and mounting evidence that women's endogenous endocrine environment influences their long term health, epidemiologic investigation of menstruation is limited. A major obstacle has been the difficulty in analyzing menstrual diary data. This paper describes the variability in menstrual cycle length in college women using a longitudinal perspective. We first characterize the distribution of cycle length and show that it can be approximated by a mixture of a nearly symmetric distribution centered at 28 days and a stochastically larger component which produces a long right tail. After assessing the degree of heterogeneity in cycling patterns, we propose an analytical approach that examines cycle lengths within the symmetric portion of the distribution and cycle lengths within the tail of the distribution separately using random effects models. PMID- 1940995 TI - The reliability of neonatal head circumference measurement. AB - Interobserver reliability in head circumference measurement was assessed in a cohort of 1105 low birthweight (less than or equal to 2000 g) infants enrolled in a study of brain hemorrhage. In 927 (83.9%) subjects, head circumference was measured both by a pediatric resident or admitting pediatrician, and by a trained ultrasound technologist. The Pearson correlation coefficient for these two sets of measurements was 0.934 (p less than 0.01), and the intraclass correlation coefficient was 0.933. By contrast, analysis of differences revealed that the limits of agreement were from -1.99 to 2.03 cm, indicating that 5% of measurements differed by 2 cm or more. Using clinicians' measurements as the gold standard, ultrasound technologists detected abnormal head circumferences with a sensitivity of 91.2%, a specificity of 97.2%, and a positive predictive value of 88.0%. For clinical purposes this level of reliability may be acceptable, but in research studies this degree of misclassification would lead to attenuation of the odds ratio. PMID- 1940997 TI - Taxonomic axes of epidemiologic study designs: a refutationist perspective. AB - Overlap among the axes of study design used for classifying epidemiologic research creates a taxonomic problem, the complexity of which may be illustrated by Venn diagrams. The diagrams also suggest a solution: to rank axes according to their bearing on study validity. This is consistent with the refutationist criterion for distinguishing strong from weak science--the potential to refute alternative explanations. In epidemiology, this means refuting confounding, reverse-causation bias, selection or allocation bias, and misclassification bias. Using susceptibility to bias as a criterion for ranking axes, a simple taxonomy emerges that is compatible with widespread usage of terminology. PMID- 1940996 TI - Impairment of physical and psychosocial function in recurrent syncope. AB - Physical and psychosocial function have rarely been assessed in syncope. We used two valid and reliable measures of health status, the Sickness Impact Profile (SIP) and the Symptom Checklist 90 (SCL-90-R), to assess functional impairment in 62 patients with recurrent syncope seen in a syncope specialty clinic. Mean total SIP scores were markedly elevated at 17 (SD = 14), indicating a level of impairment similar to severe rheumatoid arthritis and chronic low back pain. SIP psychosocial scores were significantly greater than SIP physical scores (20 vs 11, p less than 0.0001). SCL-90-R scores were also high, comparable to those of psychiatric inpatients. Somatization, anxiety and depression dimensions of the SCL-90-R were particularly elevated. SCL-90-R subscale scores were highly correlated with SIP psychosocial scores (all r greater than 0.4, and p less than 0.001). Neither age nor number of comorbid diseases correlated with measures of psychosocial function, suggesting that syncope itself causes psychosocial impairment. Although this was a referral population, these data suggest that function can be seriously impaired by syncope, that the degree of impairment is similar to that reported in other chronic diseases, and that syncope leads to significantly greater psychosocial than physical impairment. PMID- 1940998 TI - Repeated serum and urinary androgen measurements in premenopausal and postmenopausal women. AB - Intra-individual variability for serum and urinary hormones has been inadequately considered in previous studies. Therefore, in the planning phase of a prospective study of Hormones and Diet in the Etiology of Breast Cancer (ORDET study), androgen levels have been examined at two different times in 56 women (26 in premenopause and 30 in postmenopause). Hormonal measurements in serum showed a good level of agreement for both premenopause (pre) and postmenopause (post): androstenedione pre r = 0.70 (p less than 0.0001), post r = 0.77 (p less than 0.0001); testosterone pre r = 0.73 (p less than 0.0001), post log values r = 0.74 (p less than 0.0001). Dihydrotestosterone showed a good level for premenopause only: log values pre r = 0.82 (p less than 0.0001), post r = 0.41 (p less than 0.05). Agreement levels in urine were inferior to those of serum: testosterone pre r = 0.53 (p less than 0.05), post r = 0.41 (p less than 0.05); androstanediol log values r = 0.46 (p less than 0.001), post log values r = 0.57 (p less than 0.05). Correlation between the two measurements improves considering age, parity, time of blood collection and, for urine, the interval of sample collections. PMID- 1940999 TI - Relating patient characteristics at the time of admission to outcomes of hospitalization. AB - In clinical practice, physicians informally address patient characteristics such as illness severity, comorbidity, functional status and stability when considering prognosis and diagnostic or therapeutic interventions. These same attributes, more formally measured, have been used as measures of casemix in clinical research to classify patients into similar risk strata. To determine whether physician estimates of illness severity, function status and stability were predictive of morbidity, mortality, length of stay and average daily ancillary charges, a cohort of 604 patients was studied. The predictive ability of the patient characteristics were found to be outcome specific. Illness severity was a significant predictor of in-hospital morbidity and mortality, length of stay and charges (p less than 0.001). Functional status was predictive of in-hospital morbidity and mortality, 1 year mortality, length of stay and charges (p less than 0.01). Physician estimates of stability were predictive only of morbidity (p less than 0.01) and comorbidity was only a preditor of 1 year mortality (p less than 0.001). Stratifying patients on the basis of specific clinical characteristics determined at the time of admission will be useful in studies of patient outcomes and resource utilization. PMID- 1941000 TI - Gender differences in the reliability of reporting symptoms of angina pectoris. AB - Numerous studies have shown that the symptoms of angina pectoris are more prevalent in women than men, than other manifestations of coronary heart disease, with the greatest discrepancies at younger ages. Variation in symptom reliability between genders could be a potential explanation for these differences. The Lipid Research Clinics Prevalence Study included two standardized Rose Questionnaire interviews, allowing evaluation of the relationship between reliability and prevalence of angina pectoris. Analyses of the results of two interviews in 2348 men and 2085 women who were at least 30 years old in 1972-1976 showed that women generally had lower reliability estimates, but that the differences were minimal for age groups where prevalence differences were greatest. Furthermore, for interviews less than 1 month apart differences in symptom reliability were quite small (kappa = 0.65 for men and 0.58 for women). In addition, if consistently positive interviews were used to define angina, gender differences in prevalence decreased but did not disappear. In the LRC population, reporting unreliability did not explain the higher prevalence of angina pectoris in young women. PMID- 1941001 TI - Impact of liver disease on daily living in transplantation candidates. AB - The impact of different types of liver diseases on life quality in transplantation candidates was assessed. For all disease types, psychosocial impairment exceeded physical impairment. Among the various disease conditions, differences on the pattern and severity of life quality disturbances were observed. PMID- 1941002 TI - Comparison of hospital and neighborhood controls in a study of coronary artery disease. AB - Case-control studies of risk factors for coronary artery disease (CAD) have almost invariably employed hospital controls, with minimal or no coronary artery stenosis. Although there is an important advantage in knowing the CAD status of controls, such groups are subject to bias related to hospitalization. To evaluate the generalizability of results obtained from studies using hospital controls, we compared risk factors in 342 hospital controls free of angiographic evidence for CAD, 168 neighborhood controls without symptoms of CAD, and 450 CAD patients. Coronary artery disease in cases and hospital controls was established arteriographically. No significant differences were found between the male control groups for total and low density lipoprotein (LDL) cholesterol, LDL apo B, pack-years of smoking, body mass index, proportion with hypertension, diabetes and family history of coronary heart disease. Compared with neighborhood controls, male hospital controls had significantly lower high density lipoprotein (HDL) cholesterol, higher triglycerides and uric acid and scored higher on the Framingham Type A behavior pattern scale. Among women, the hospital control group had significantly lower LDL cholesterol and fewer pack-years of smoking, and a greater prevalence of hypertension than the neighborhood group. A greater proportion of both male and female hospital controls had left ventricular hypertrophy, and there were more current smokers among the neighborhood controls in both sexes. Age adjustment did not change these comparisons. While very few neighborhood controls were treated with beta-blockers, 32.7% of male and 41.4% of female hospital controls were so medicated. Control for beta-blocker use eliminated the difference in HDL cholesterol and triglycerides between the two male control groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941003 TI - Comparison of recruitment strategies for a large-scale clinical trial in the elderly. AB - Formal evaluation of recruitment strategies for clinical trials conducted in the community setting, rather than in hospitals, is limited despite recruitment rates and costs having significant implications for the planning of large trials. As part of the development of a large-scale primary prevention trial of low-dose aspirin in 15,000 elderly persons (aged 70 years and above) to be undertaken in a community setting, a pilot study involving 400 participants was carried out to evaluate different recruitment strategies. Three techniques were compared: recruiting from the electoral roll (by individual invitation using direct mail), local community approach (through retirement villages, local media, elderly community groups), and using general/family practice (identifying persons over 70 within a practice and direct mail invitation to participate). Screening of potential participants was carried out by a trained trial nurse with limited involvement only of medical practitioners. The target recruitment figure was achieved in 4 months using the equivalent of 1.5 full-time nurses. General practice was the most effective method utilized, with a yield of one participant recruited per six approached at an estimated cost of A$48.36 per recruited participant. This compares with yield rates of 1 per 29 (for the local community approach) and 1 per 17 for the electoral roll, and costs per participant of A$42.54 and A$59.37 respectively. Other less tangible benefits of general practice include the greater cooperation of primary care practitioners in patient follow-up and end-point ascertainment. PMID- 1941004 TI - Taking things apart and the art of arrangement. PMID- 1941005 TI - Validity of case simulations. PMID- 1941006 TI - Imprecision of the clinical diagnosis of coronary heart disease in epidemiological studies and atherogenesis. AB - Coronary heart disease (CHD) is an imprecise diagnosis associated with a substantial diagnostic error and provides an erroneous assessment of the morbidity and mortality of myocardial ischemia and of severe coronary atherosclerosis. Due to the inability to measure the severity of atherosclerosis during life, epidemiologists frequently use the incidence of CHD as a surrogate monitor of severe atherosclerosis. It is therefore important in clinical epidemiological studies to appreciate the degree of inaccuracy of CHD statistics, which detracts from the value of such studies and their reliability. PMID- 1941007 TI - "Prudence" in disease prevention. PMID- 1941008 TI - Natural history of chronic left ventricular aneurysm; a population based cohort study. AB - In order to evaluate the morbidity and mortality of chronic left ventricular aneurysm a population based cohort study was carried out. All cardiac catheterizations performed in Iceland during the years 1983-1985 were examined (n = 1261). Sixty seven patients with left ventricular aneurysm defined as: (1) normal diastolic contour with segmental dyskinesis (n = 6), (2) abnormal diastolic contour with (a) akinetic (n = 36) or (b) dyskinetic (n = 25) segments in systole, were included. Sixty seven patients with normal diastolic contour and akinetic segments in systole served as controls. The groups had similar mean age, sex ratio, number of diseased vessels and left ventricular end diastolic pressure. Mean ejection fraction was significantly lower in the aneurysm group (46 vs 56%, p = 0.00005). Collaterals were detected significantly more often in controls (88 vs 72%, p = 0.03). At follow up in 1989, 19 in the aneurysm group had died as compared to 12 in the control group. Life table analysis revealed significant differences between survival curves. The relative risk ratio was 2.18 with 95% confidence interval of 1.00-4.74 (p less than 0.05). However, when the amount of myocardial damage was taken into account the differences in survival were no longer statistically significant (relative risk ratio 1.77 with 95% confidence interval of 0.79-3.99). We conclude that the reduced survival probability of patients with chronic left ventricular aneurysm in comparison to controls with akinetic scars is accounted for by the more extensive myocardial damage and not by the presence of aneurysm per se. PMID- 1941009 TI - Assessing predictive accuracy: how to compare Brier scores. AB - Several investigators have used the Brier index to measure the predictive accuracy of a set of medical judgments; the Brier scores of different raters who have evaluated the same patients provides a measure of relative accuracy. However, such comparisons may be difficult to interpret because of the lack of a statistical test for differentiating between two Brier scores. To demonstrate a method for addressing this issue we analyzed the judgments of five medical students, each of whom independently evaluated the same 25 patients with recurrent chest pain. Using the method we determined that two of the students gave judgments that were incompatible with the actual observed outcomes (p less than 0.05); of the three remaining students we detected a significant difference between two (p less than 0.05). These results differed from receiver operating characteristic curve area analysis, another technique used to evaluate predictive accuracy. We suggest that the proposed method can provide a useful tool for investigators using the Brier index to compare how well clinicians express uncertainty using probability judgments. PMID- 1941010 TI - Epidemiology of headache in a general population--a prevalence study. AB - We present the first prevalence study of specific headache entities using the operational diagnostic criteria of the International Headache Society. One thousand 25-64 year old men and women, who lived in the western part of Copenhagen County were randomly drawn from the Danish National Central Person Registry. All subjects were invited to a general health examination focusing on headache and including: a self-administered questionnaire concerning sociodemographic variables, a structured headache interview and a general physical and neurological examination. The participation rate was 76%. Information about 79% of the non-participants showed a slightly differing headache prevalence which was not quantitatively important. The following results in participants are therefore representative of the total sample. The lifetime prevalences of headache (including anybody with any form of headache), migraine, and tension-type headache were 93, 8 and 69% in men; and 99, 25 and 88% in women. The point prevalence of headache was 11% in men and 22% in women. Prevalence of migraine in the previous year was 6% in men and 15% in women and the corresponding prevalences of tension-type headache were 63 and 86%. Differences according to sex were significant with a male: female ratio of 1:3 in migraine, and 4:5 in tension-type headache. The prevalence of tension-type headache decreased with increasing age, whereas migraine showed no correlation to age within the studied age interval. Headache disorders are extremely prevalent and represent a major health problem, which merits increased attention. PMID- 1941011 TI - Childhood brain tumor risk in relation to birth characteristics. AB - A population-based case-control study was conducted utilizing linked cancer registry and birth certificate data to examine potential associations between selected birth characteristics and the occurrence of brain tumors in children. Cases (n = 157) were those children ages 10 and under who were born in Washington state and who were diagnosed with a primary brain tumor between 1974 and 1986. Controls were randomly selected from the Washington State birth files and were matched 5:1 to cases on year and county of birth. A limited number of positive findings emerged from the study. Results suggested that high birthweight may be related to an increased risk of childhood brain tumor (odds ratio (OR) = 1.4, 95% CI 1.0-2.0 for all histologies combined; OR = 1.9, 95% CI 1.1-3.1 for astrocytomas). The risk of astrocytoma was also observed to be associated with older maternal age (OR = 2.2, 95% CI 1.2-4.0) and a history of prior fetal death(s) (OR = 1.9, 95% CI 1.0-3.8). PMID- 1941012 TI - Functional capacity in two elderly populations aged 75 or over: comparisons at 10 years' interval. AB - The functional capacity of two different non-institutionalized elderly populations and the resources available were compared in the same geographical area at 10 years' interval. The study shows that a 1.5-fold increase in the non institutionalized population aged 75 or over combined with a fixed number of institutional beds in 10 years resulted in more disability among the elderly at home. The nursing home population at the latter point of time was older and showed a higher mortality, indicating increased pressure and selection to the nursing home. The first study comprised 82.8% and the second 89.2% of all community-living persons aged 75 or over. In 1988, the functional status of the aged living at home was significantly lower than in 1978, in 8 out of 12 functional activities of daily living (ADL). The Basic ADL Index decreased significantly both in men and in women, and mobility also deteriorated. The Instrumental ADL Index decreased significantly in men, while the Index was equally poor in women in both interviews. The poor functional status of the elderly in 1988 was accompanied by moving to the town centre and considerably improved housing standards. Home care services had more than doubled, and home nursing visits had also increased. PMID- 1941013 TI - Strategies of prevention revisited: effects of imprecise measurement of risk factors on the evaluation of "high-risk" and "population-based" approaches to prevention of cardiovascular disease. AB - Imprecise measurement of risk factors causes misclassification of individuals, limits sensitivity to detect those with high true levels, and dilutes associations between risk factors and disease. The implications of these effects for two particular examples were explored using data from a large prospective study relating plasma cholesterol to coronary heart disease (CHD) mortality and diastolic blood pressure (DBP) to fatal stroke. The absolute and relative effectiveness of three "high-risk" strategies of screening and treatment and a "population-based" shift in the risk factor distribution were compared, assuming different degrees of measurement error. The absolute benefits of each strategy were greater than suggested by unadjusted estimates from survey data. For cholesterol and CHD (a linear relationship in this cohort), uncorrected estimates tended to exaggerate the effectiveness of "high-risk" strategies relative to the "population-based" approach. For DBP and stroke (an exponential relationship), the relative effectiveness of screening and treatment was underestimated if no allowance was made for measurement error. These findings are strictly applicable only to the middle-aged men from whom they were derived, but the effects of misclassification and regression dilution need to be considered in any assessment of preventive strategies. PMID- 1941014 TI - The relationship between body mass and breast cancer among women enrolled in the Cancer and Steroid Hormone Study. AB - We examined the relationship between body mass [weight (kg)/height (m)2] and breast cancer using data from the Cancer and Steroid Hormone Study. The study compared 4323 women aged 20-54 years with newly diagnosed breast cancer identified through population-based tumor registries with 4358 women randomly selected from the general population of the same geographic areas. Among naturally menopausal women, risk of breast cancer increased with increasing body mass index (BMI); those severely overweight (BMI greater than or equal to 32.30) had nearly 3-fold higher risk of breast cancer compared with women in the leanest category (BMI less than 20.00). This positive association appeared stronger with increasing years since menopause and in women who had ever used estrogen replacement therapy. A positive association between body mass and breast cancer risk also was observed among premenopausal women; however, risk estimates were substantially lower. Substantial weight gain from adolescence to adulthood was a more important risk factor than lifelong obesity. Prevalence of obesity increases with age; our results suggest that interventions that prevent this trend could have an important effect on breast cancer risk, especially during the menopausal years. PMID- 1941015 TI - The association of physical activity and diabetic complications in individuals with insulin-dependent diabetes mellitus: the Epidemiology of Diabetes Complications Study--VII. AB - The relationship between leisure-time physical activity and diabetes complications was examined in 628 individuals with insulin-dependent diabetes mellitus. Neuropathy was based upon clinical exam; retinopathy by fundus photographs; nephropathy by urine samples and macrovascular disease by clinician diagnosis. Past week physical activity was found to be inversely related to complication status but since current inactivity could be the result of the complications, historical activity (estimated leisure activity during ages 14-17) was also examined in relation to complication status. Males reporting higher levels of historical physical activity had a significantly lower prevalence of nephropathy and neuropathy but not retinopathy as demonstrated by multivariate analysis (controlling for duration of disease, age, and current activity levels). The lack of similar findings in women may be due to their low levels of reported physical activity. The consistent relationship between historical leisure physical activity and development of complications in males suggests that activity may be protective or at least not detrimental to the individual with insulin-dependent diabetes. PMID- 1941016 TI - The case-control design and the assessment of the efficacy of cancer screening. AB - Case-control studies have been used in recent years to evaluate the efficacy of cancer screening. However, relatively little work has been done to examine the methodology itself for this purpose. In this paper, it is demonstrated that because of self-selection bias the case-control study can yield a biased estimate of screening efficacy. Further, it is shown how this bias can be assessed using data from a randomized trial. Using data from the HIP breast cancer screening study, the magnitude of the self-selection bias is estimated and is seen to be substantial. PMID- 1941017 TI - How independent are "independent" effects? Relative risk estimation when correlated exposures are measured imprecisely. AB - A relative risk estimate which relates an exposure to risk of disease will tend to be estimated too close to unity if that exposure is subject to random measurement error or intra-subject variability. "Independent" relative risk estimates, for the effect of one exposure after adjusting for confounding exposures, may be biased in either direction, depending on the amount of measurement imprecision in the exposure of interest and in the confounders. We describe two methods which estimate the bias in multivariate relative risk estimates due to the effect of measurement imprecision in one or more of the exposure variables in the model. Results from the two methods are compared in an example involving HDL cholesterol, triglycerides and coronary heart disease. In this example, the degree of bias in relative risk estimates is shown to be highly dependent on the amount of measurement imprecision ascribed to the exposures. It is concluded that when two exposures are substantially correlated, and one or both is subject to sizeable measurement imprecision, a study in which exposures are measured only once will be inadequate for investigating the independent effect of the exposures. Where feasible, epidemiologists should seek study populations where the correlation between the exposures is smaller. PMID- 1941018 TI - How soon after quitting smoking does risk of heart attack decline? AB - A population-based case-control study (involving 1282 cases and 2068 controls) was conducted to examine the risk of myocardial infarction or coronary death after cigarette smokers quit smoking. The odds ratios for current smokers were significantly elevated compared to non-smokers (OR = 2.7 for men and OR = 4.7 for women). For ex-smokers odds ratios declined rapidly after quitting and after about 3 years they were not significantly different from unity. Fibrinogen concentrations measured in the controls only were higher in current smokers and ex-smokers up to 2 years after quitting than in non-smokers and after that time were similar to levels in non-smokers; however, most of the differences among categories of smokers were not statistically significant. These results support the hypothesis that risk of a coronary event in ex-smokers declines rapidly after quitting and within 2-3 years is similar to the risk for non-smokers. PMID- 1941019 TI - Physical activity, dietary habits and adenomatous polyps of the sigmoid colon: a study of self-defense officials in Japan. AB - Physical activity and dietary habits were compared between 80 men with adenomatous polyps of the sigmoid colon and 1148 men with normal colonoscopy among male retiring self-defense officials. Physical activity as expressed in terms of time spent doing strenuous activities during leisure time was inversely related to the risk of adenomatous polyps. Controlling for rank, smoking, alcohol and body mass index (BMI), odds ratios for the categories of 0, 1-59, 60-119 and greater than or equal to 120 minutes per week were 1.0, 0.88, 0.70 and 0.44, respectively (trend p = 0.015). Among a limited range of foods and beverages, the consumption of rice, green tea and instant coffee tended to be associated with a decreased risk of adenomatous polyps. Although the associations observed with dietary habits still need to be substantiated, the findings on physical activity lend further evidence to the hypothesis that physical activity may be protective in the development of colon cancer. PMID- 1941021 TI - Trichotomous decisions do not imply trichotomous tests. PMID- 1941020 TI - Using ordinal logistic regression to estimate the likelihood of colorectal neoplasia. AB - The utility of ordinal logistic regression in the prediction of colorectal neoplasia was demonstrated in a group of 461 consecutive patients undergoing colonoscopy in a community practice. One hundred twenty-nine patients had adenomatous polyps and 34 had colorectal adenocarcinoma. An ordinal logistic regression model developed in a random subset (292 patients) identified five predictors of colorectal neoplasia. Colorectal neoplasia risk could be predicted using the patient's age, sex, hematocrit, fecal occult blood test result and indication for colonoscopy. The risk of colorectal neoplasia in the remaining subset of patients (169) could be reliably estimated from the model. Ordinal logistic regression analysis in this select group of patients can accurately estimate the likelihood of colorectal neoplasia. Because the generalizability of our findings are unknown, the model should not be applied to other patients. However, application of this technique to an unselected group of patients not already referred for colonoscopy could provide unbiased estimates of colorectal neoplasia risk in individual patients. PMID- 1941022 TI - Differential recall as a source of bias. PMID- 1941023 TI - Structured abstracts of proposals for clinical and epidemiological studies. PMID- 1941024 TI - Structured abstracts: a modest dissent. PMID- 1941025 TI - An overview of body weight of older persons, including the impact on mortality. The National Health and Nutrition Examination Survey I--Epidemiologic Follow-up Study. AB - The authors studied distributions of body weight for height, change in body weight with age, and the relationship between body mass index and mortality among participants in the Epidemiologic Follow-up Study of the first National Health and Nutrition Examination Survey (NHEFS) (n = 14,407), a cohort study based on an representative sample of the U.S. population. Percentiles of body weight for height according to age and sex are presented. Cross-sectional analyses of body weight suggest that mean body weight increases with age until late middle age, then plateaus and decreases for older aged persons. However, longitudinal analysis of change in weight with age shows that younger persons in the lower quintile at baseline tend to gain more than those in the higher quintile. Older persons in the higher quintile at baseline have the greatest average loss in weight. The relationship of body mass index to mortality is a U-shaped curve, with increased risks in the lowest and highest 15% of the distribution. Increased risk of mortality associated with the highest 15th percentile of the body mass index distribution, as well as the highest 15% of the joint distribution of body mass index and skinfold thickness, is statistically significant for white women. However, the risk diminishes when adjusted for the presence of disease and factors related to disease. More noteworthy is the fact that there is a statistically significant excess risk of mortality for both race and sex groups in the lowest 15% of the body mass index distribution after adjusting for smoking history, and presence of disease. Those in the lowest 15% of the joint body mass index and skinfold thickness distribution, were also at increased risk. Risk of mortality for both men and women who have lost 10% or more of their maximum lifetime weight within the last 10 years is statistically significant, even when controlling for current weight. This study has replicated previously reported relationships, while correcting for several methodological issues. PMID- 1941027 TI - Likelihood ratios with confidence: sample size estimation for diagnostic test studies. AB - Confidence intervals are important summary measures that provide useful information from clinical investigations, especially when comparing data from different populations or sites. Studies of a diagnostic test should include both point estimates and confidence intervals for the tests' sensitivity and specificity. Equally important measures of a test's efficiency are likelihood ratios at each test outcome level. We present a method for calculating likelihood ratio confidence intervals for tests that have positive or negative results, tests with non-positive/non-negative results, and tests reported on an ordinal outcome scale. In addition, we demonstrate a sample size estimation procedure for diagnostic test studies based on the desired likelihood ratio confidence interval. The renewed interest in confidence intervals in the medical literature is important, and should be extended to studies analyzing diagnostic tests. PMID- 1941026 TI - Alcohol consumption and the risk of breast cancer: a report from the Tecumseh Community Health Study. AB - The relationship between prior alcohol consumption and the risk of breast cancer was studied in 1954 women in the Tecumseh Community Health Study (TCHS) who entered the cohort in 1959-1960 and were followed potentially for 28 years. The mean alcohol consumption at baseline was 0.89 (SD 2.2) oz/week for premenopausal women and 0.85 (SD 2.2) oz/week for postmenopausal women. Only 25% of the cohort consumed more than 0.5 oz of ethanol/week or about 1.6 g/day. The adjusted relative risks (RRs) for breast cancer associated with the use of ethanol vs never drinking were 0.93 (95% CI, 0.40-2.18) for ex-drinkers, 1.08 (95% CI, 0.64 1.82) for 0- less than 1 drink/day, 1.23 (95% CI, 0.49-3.10) for 1- less than 2 drinks/day and 1.12 (95% CI, 0.25-5.01) for greater than or equal to 2 drinks/day. There were only 37 subjects in the group at the highest level of consumption (greater than or equal to 2 drinks/day). There was no significant interaction between alcohol and the period of onset of breast cancer (premenopausal or postmenopausal). In the TCHS, alcohol consumption generally at levels not exceeding 2 drinks/day, was not significantly associated with an increased risk of breast cancer. Although we have found little excess risk associated with alcohol consumption, the wide confidence intervals summarized above are not inconsistent with previously published reports that have suggested a modest positive association. PMID- 1941028 TI - A randomized controlled trial comparing quantitative informed consent formats. AB - Informed consent has been indirectly studied only in settings that do not replicate the actual consent process. We designed a sham study and randomly allocated adult ambulatory patients to receive one of two consent forms: Consent A (n = 52) described a randomized trial of usual treatment vs a new medication that "may work twice as fast as the usual treatment"; or Consent B (n = 48) that described a randomized trial of a new medication that "may work half as fast as the usual treatment". Patients randomized to Consent A were more likely to consent than those randomized to Consent B (consent rate A = 67%, consent rate B = 42%, p less than 0.01). Among patients who cited quantitative information, the difference in consent rate was even more marked (95% vs 36%, p less than 0.001); patients who did not cite quantitative information had equivalent consent rates. Patients who perceived minimal or severe symptoms had lower consent rates than those with mid-range symptom scores (chi 2(2) = 8.35, p = 0.015). Patients who recognize quantitative information will use it to make informed consent decisions. PMID- 1941029 TI - Comparison of perceived health status and conventional functional evaluation in stable patients with coronary artery disease. AB - A cross-sectional study of stable coronary hospital patients was carried out to compare perceived health assessment with conventional clinical measures; 93 consecutive patients were studied, 45 of whom had undergone bypass surgery. Exercise tests and clinical functional classification were obtained together with blind concurrent self-responses to the Nottingham Health Profile (NHP), a measure of distress. Coronary arteriography was available for all patients. Patients with negative exercise tests had lower NHP scores (lower levels of distress) than those with positive or inconclusive tests, especially in the energy, pain and physical mobility NHP dimensions (p less than 0.01). High Spearman correlation coefficients were found between exercise performance and energy (rs = -0.51) and pain (rs = -0.36) scores. This correlation was closer than that found with clinical functional class. In these patients, exercise performance closely correlated with perceived distress. Self-perceived health status measures may improve the evaluation of coronary patients based on clinical assessment alone. PMID- 1941030 TI - Weight and mortality in Finnish women. AB - Mortality in relation to body mass index (BMI) was studied in 17,159 healthy Finnish women aged 25-79 followed up for a median of 12 years. Mortality from all cases was related to BMI only in non-smokers aged 25-64, among whom the mortality pattern was "U"-shaped, with a minimum in the second quintile of BMI (the reference range), and about 1.5 times higher in quintiles I and V. Most of the excess risk of mortality among overweight women was due to cardiovascular diseases. During the first 7 years of follow-up, and high risk (relative risk (RR) = 1.7, 95% confidence interval (CI) = 1.0-2.9 for quintile V compared to quintile II) depended on the association of BMI with the initial blood pressure level, but in the later years, the relative risk of cardiovascular death, ranging from 1.6 (95% CI = 1.0-2.5) for women in quintile III up to 2.6 (95% Ci = 1.7 4.0) for those in quintile V, was largely independent of the baseline levels of the main biological risk factors. The excess mortality among thin women under the age of 65 was mainly due to non-cardiovascular diseases (RR = 1.7, 95% CI = 1.2 2.3 for quintile I compared to quintile II) and was not attributable to antecedent disease, smoking or the biological risk factors studied. Among women aged 65 and over, overall mortality varied little with BMI, but thinness seemed to predict deaths from cancers (RR = 1.6, 95% CI = 0.9-3.0).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941031 TI - Concordance of ischemic heart disease in the NHLBI twin study after 14-18 years of follow-up. AB - Morbidity and mortality were assessed in the NHLBI twin study at the end of 1987. Deaths were greater in DZ twins (58/520, 11.2%) than MZ twins (38/508, 7.5%). Ischemic heart disease concordances were 2.3 times higher in MZ pairs and 2.8 times higher in DZ pairs than expected based on the prevalence of ischemic heart disease in the cohort. Family history scores for heart disease, calculated 14-18 years earlier at entry to the study, were significantly higher in DZ pairs where one or both members later developed ischemic heart disease and in corcordant MZ pairs than in twin-pairs without any subsequent heart disease. Concordance rates were not significantly different between MZ and DZ pairs. The results agree with previous suggestions that selection at enlistment into the armed services over 40 years ago, as well as later volunteering for the NHLBI twin study, resulted in a decline in the number of concordant MZ pairs. PMID- 1941032 TI - The role of socioeconomic factors in the survival of patients with colorectal cancer in Saarland/Germany. AB - The role of socioeconomic factors in the survival of patients with colorectal cancer was assessed using data from the cancer registry of Saarland/Germany, and census information. Among 2627 patients with colorectal cancer diagnosed from 1974 to 1983, patients from communities in the lowest of three categories defined by socioeconomic factors showed significantly lower survival rates than patients from other communities. After adjustment for potential biological and other sociogeographic risk factors in multivariate analyses, relative hazard of death associated with low socioeconomic status (SES) compared with high SES was estimated to be 1.22 (95% CI: 1.01-1.47) for colon cancer and 1.32 (95% CI: 1.09 1.60) for rectum cancer. The results are in agreement with earlier studies from North America, Hawaii and Sweden and indicate that an attempt to improve health care services and acceptance and possibly other relevant general living conditions in socioeconomically less privileged communities may be a rewarding approach towards increasing survival of patients with colorectal cancer. PMID- 1941033 TI - The cholesterol trap: how doctors and patients could avoid overevaluation of a single cholesterol value. PMID- 1941034 TI - Pharmacoepidemiology and clinical research. PMID- 1941035 TI - Drugs as determinants of health and disease in the population. An orientation to the bridge science of pharmacoepidemiology. PMID- 1941036 TI - Judging the effectiveness of antihypertensive therapy in an individual patient. AB - The physician's decision as to whether a hypertensive drug has produced satisfactory blood pressure lowering is more difficult than it is usually perceived to be. Variability of blood pressure, regression to the mean and habituation to the taking of blood pressure all conspire to blur the significance of the observed drop. We present algorithms outlining the number of visits before and after the initiation of therapy and the mmHg drop required for determination with acceptable certainty that any response to the hypotensive drug has occurred. Our conclusion is that the variability of blood pressure limits the clinician's ability to confidently conclude that antihypertensive therapy is effective unless the change in blood pressure exceeds a relatively high threshold and/or the number of visits both before and after the initiation of antihypertensive therapy is large. Because regression to the mean will be minimized, fewer visits and/or a lesser blood pressure fall in the treated patient changing or adding medications will be necessary to determine that a real decline has occurred. PMID- 1941037 TI - Methodological standards for assessing therapeutic equivalence. AB - This paper reviews issues related to defining and demonstrating therapeutic equivalence. A set of guidelines are proposed to critically review clinical trials to determine whether there is sufficient evidence to conclude that an experimental therapy is therapeutically equivalent to a standard one. These guidelines include criteria for assessing whether imprecision pertaining to the measurement of outcomes impinges on the validity of an equivalence test. PMID- 1941038 TI - Pharmacoepidemiology in pre-approval clinical trial safety monitoring. AB - Applications of pharmacoepidemiology to the pre-approval safety monitoring of investigational drugs are examined and compared with the post-approval applications. Pre-approval epidemiologic assessments of drug safety can complement clinical assessments of rare, serious adverse events occurring in open label uncontrolled clinical trials. Applications include retrospective identification of patient risk factors for adverse drug events and incidence comparisons based on historical controls. While similar in concept to applications of pharmacoepidemiology in the analyses of uncontrolled open label post-marketing surveillance studies, answers are often needed in days rather than weeks and the emphasis is on whether human studies can continue. Advance planning of historical data sources is essential as is an effective clinical trial data management system. Implications for methodologic research and for drug development are discussed. PMID- 1941039 TI - Why has the utilization of antiasthmatics increased in Finland? AB - The sales of antiasthmatics have increased rapidly in the Nordic countries during the 1980s. The causes for this growth in Finland were studied. Four nationwide population surveys show that the prevalence of self-reported asthma has risen, a larger proportion of asthmatic patients are under medication, the number of antiasthmatics per patient has increased, and the dosage recommendations of inhalation glucocorticoids and beta-agonists have grown. The average cost of medical treatment of an asthmatic patient was FIM 1848 (approximately U.S. $510.00) in 1990. The highest average expenses in the 21 districts studied were FIM 2171 and the lowest FIM 1535. To identify the consequences of these variations, the frequency of symptomatic periods as well as the quality of life of the asthmatic patients should be studied. PMID- 1941040 TI - Baldness and coronary disease. PMID- 1941041 TI - Right ventricular dysfunction. PMID- 1941043 TI - Assessment of right heart function. AB - Growing recognition of the contribution of right heart function to cardiac output in a variety of pathologic conditions lends a new outlook to cardiac assessment, especially when cardiac output is inadequate for physiologic needs. Signs and symptoms of right heart dysfunction made by physical assessment can be validated by radiologic techniques as well as a newly available bedside method of thermodilution determination of right ventricular ejection fraction and right ventricular end-diastolic and end-systolic volumes. Assessment of right ventricular function can aid clinical decision making when pressure readings obtained by usual hemodynamic monitoring techniques are altered by changes in intrathoracic pressure or ventricular compliance. This article reviews physical assessment of right heart function, signs and symptoms of right heart dysfunction, radiographic evaluations and their limitations and introduces the thermodilution evaluation of right ventricular performance. Clinical examples are presented to illustrate the utility of this new technique along with selected nursing diagnoses and outcome criteria. PMID- 1941042 TI - The right ventricle: significant anatomy, physiology, and interventricular considerations. AB - The crucial role of the right ventricle for optimal global cardiac function has only recently become appreciated. Once thought of as dispensable, the right ventricle now is viewed as an integral component of biventricular function. Key anatomical and physiological differences between the ventricles affect the right heart's response to alterations in the determinants of cardiac output. Disruption of the strong interrelationship between the two ventricles can lead to the pathophysiologic sequelae of biventricular failure. PMID- 1941045 TI - Right ventricular myocardial infarction. AB - Right ventricular myocardial infarction (RVMI) is recognized as an important clinical entity. The clinical course of patients with RVMI may be benign, or it may progress to profound hypotension and cardiogenic shock. The medical and nursing management of these patients differs significantly from that of patients with left ventricular infarction. The nurse must be familiar with the clinical signs and medical treatment of RVMI to facilitate early diagnosis and to plan appropriate acute and long-term nursing management of these patients. PMID- 1941044 TI - Electrocardiographic assessment of right heart dysfunction. AB - The electrocardiogram, when used in light of other clinical data, can be a powerful tool in detecting right heart dysfunction. Right bundle branch block can be identified on the electrocardiogram by the presence of an RSR' configuration in right-sided chest leads. Right atrial enlargement produces tall pointed P waves in lead II and biphasic P waves in V1, whose initial upstroke is larger than the terminal downstroke. Right ventricular enlargement is best seen on the electrocardiogram by a reverse in the pattern of normal R wave progression across the precordium. Occurring most often with an inferior wall myocardial infarction, a right ventricular infarction is depicted by ST segment elevations in right sided precordial leads. The ability to detect these electrocardiographic changes will enhance the nurse's assessment and management of patients with right heart dysfunctions. PMID- 1941046 TI - Noncardiogenic mechanisms of right heart dysfunction. AB - Alterations in right ventricular (RV) performance are critical to the cardiac dysfunction witnessed in adult respiratory distress syndrome (ARDS), septic shock (SS), and as a consequence of positive end-expiratory pressure (PEEP) administration during mechanical ventilation. The authors review evidence for right heart dysfunction in these circumstances. In ARDS, an increase in RV afterload with the onset of pulmonary artery hypertension is the predominant factor promoting RV dysfunction. In SS, most investigators agree that a primary decrease in myocardial contractility is the major factor limiting RV performance. The application of PEEP during mechanical ventilation can potentiate alterations in RV preload, afterload, and/or contractility, all of which promote RV dysfunction and compromise left ventricular filling. As RV dysfunction may seriously affect global myocardial performance in all of these settings, the clinician must identify that RV function is impaired, discern the contributing mechanism, and select an appropriate therapeutic regimen targeted at addressing this predominant mechanism. Assessment and management strategies are described. PMID- 1941047 TI - Interventions to support the failing right ventricle. AB - Right ventricular failure is a critical event that quickly improves or deteriorates. Interventions to support the failing right ventricle are extensive, beginning with adequate volume loading and vasopressor support. If these methods are not effective, invasive support is instituted, including intrapulmonary artery balloon counterpulsation and ventricular assist devices. This article discusses volume loading and vasopressive therapy, including drugs and doses. Invasive therapy of intrapulmonary artery balloon counterpulsation and ventricular assist devices are included, as well as institution and weaning procedures. Appropriate nursing considerations and interventions are outlined in detail. PMID- 1941048 TI - Case study in perioperative right heart failure. AB - Today, we are increasingly aware of the important role the right ventricle plays in maintaining hemodynamic stability. When the right ventricle fails, added stress is placed on the cardiovascular system. This article focuses on patients with perioperative right heart failure and the associated complex nursing care that is needed to manage these patients. Three major nursing diagnoses are reviewed, including decreased cardiac output, impaired gas exchange, and high risk for ineffective family coping. PMID- 1941049 TI - Monitoring right ventricular function. AB - A new catheter developed by Edwards Critical-Care Division measures right ventricular ejection fraction and calculates right ventricular stroke volume, end systolic volume, and end-diastolic volume. The nurse can thus assess a patient's right ventricular function curves using the relationship between stroke volume and end-diastolic volume. This article critiques a study that used this new technology and discusses implications for clinical practice and nursing research. PMID- 1941050 TI - On clinical trial participation. PMID- 1941051 TI - Poorly differentiated carcinoma of unknown primary site: clinical usefulness of immunoperoxidase staining. AB - To assess the clinical utility of immunoperoxidase tumor-cell staining in patients with poorly differentiated carcinoma of unknown primary site, we performed a battery of stains on tumors from 87 patients treated between August 1978 and April 1983. Poorly differentiated carcinoma or poorly differentiated adenocarcinoma was diagnosed on the basis of light microscopic examination, and all patients were treated before the technology of immunoperoxidase staining was routinely used. Therefore, results of immunoperoxidase staining can be correlated with clinical outcome in this group of similarly treated patients with a long median follow-up. Immunoperoxidase staining confirmed the diagnosis of poorly differentiated carcinoma in 49 patients (56%) and yielded other diagnoses in 14 patients (16%): melanoma, eight; lymphoma, four; prostatic carcinoma, one; and yolk sac carcinoma, one. In 24 patients (28%) the immunoperoxidase staining pattern was inconclusive; electron microscopy was usually helpful in clarifying the diagnosis in these patients. Seventy-five patients (86%) received combination chemotherapy with a cisplatin-based regimen, and 24 patients (28%) had a complete response. Nine of these patients were later given specific diagnoses by immunoperoxidase staining (lymphoma, four; melanoma, four; yolk sac tumor, one). All patients with an immunoperoxidase diagnosis of lymphoma also had clinical features compatible with lymphoma and are long-term survivors. Patients with immunoperoxidase features suggesting melanoma were surprisingly responsive to chemotherapy, with three of seven complete responses and two long-term survivors. Patients with melanoma diagnosed by immunoperoxidase staining should not be excluded from a trial of cisplatin-based therapy. Immunoperoxidase staining is useful in the routine evaluation of metastatic poorly differentiated carcinoma of unknown primary site, as it can occasionally suggest the lineage of the tumor and have specific therapeutic implications. PMID- 1941052 TI - Phase II trial of carboplatin plus cisplatin in recurrent and advanced squamous cell carcinoma of the head and neck. AB - Cisplatin is one of the most active chemotherapeutic agents for the treatment of squamous carcinoma of the head and neck; however, neurotoxicity and nephrotoxicity are dose-limiting. The analog, carboplatin, is a promising new agent with similar activity but a different spectrum of toxicity. To evaluate if a therapeutic advantage could be achieved with acceptable toxicity, a combination of carboplatin 350 mg/m2 and cisplatin 50 mg/m2 were administered every 28 days to patients with recurrent or metastatic disease who had received no prior chemotherapy. Of 24 patients enrolled in this study, 21 were assessable for response and toxicity. Five partial responses were observed (24%; 95% confidence interval [Cl], 4.9% to 38.6%). No complete response occurred. Two of these patients received definitive radiotherapy and achieved complete responses. The median survival of all patients was 24 weeks. Hematologic toxicity was dose limiting necessitating a decrease in the starting dose of carboplatin to 300 mg/m2. Nonhematologic toxicity was infrequent and mild. Significant renal impairment occurred in only two patients. Although treatment with the combination of carboplatin and cisplatin is feasible, we found no therapeutic advantage in terms of an increased response or survival. PMID- 1941053 TI - Maternal and fetal outcome after invasive cervical cancer in pregnancy. AB - Invasive carcinoma of the cervix is the most common gynecologic malignancy to occur during the reproductive years. To analyze the effects of pregnancy on the course and survival of invasive cervical cancer, we compared 40 women with invasive cervical cancer to 89 nonpregnant controls matched for age, calendric year of diagnosis, stage, and tumor type. Additionally, we compared the distribution of invasive cervical cancer stages among the 40 pregnant women with that among the 1,963 cases of invasive cervical cancer treated during the same 30 years in women less than 45 years of age registered in the same hospital. To evaluate pregnancy outcome, we compared babies born to women with invasive cervical cancer to babies born of women matched for maternal age and not exposed to known teratogens or reproductive risks during pregnancy. Thirty-year survival of pregnant women with invasive cervical cancer was identical to that of their matched controls. Women having invasive cervical cancer were 3.1 times more likely to be diagnosed with stage I disease (95% confidence interval, 1.6 to 6.2). Additionally, they had a significantly lower chance of being diagnosed with stages III and IV (P = .02). Babies born to women with invasive cervical cancer were similar in gestational age and rates of prematurity but had a lower birth weight than the matched controls. There were two stillbirths among the 24 pregnancies that continued to term (8%), not statistically different from the 1.1% rate for Ontario. Our data suggest that pregnancy per se does not adversely affect the survival of women with invasive cervical cancer. However, this study provides evidence that pregnant women are more likely to present with early disease because of regular, pregnancy-related obstetric exams. Moreover, there is an increased risk for stillbirth, which should lead to follow-up of these patients by a high-risk perinatal unit. PMID- 1941054 TI - Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study. AB - Ninety-six assessable patients with advanced or recurrent uterine sarcomas, who were no longer controllable with surgery and radiotherapy, and who had not received prior chemotherapy were treated with cisplatin 50 mg/m2 intravenously every 3 weeks. Of 63 cases with mixed mesodermal tumors, five complete responses (CRs; 8%) and seven partial responses (PRs; 11%) were observed (95% confidence interval [CI], 10.3% to 30.9%). Of 33 patients with leiomyosarcoma, one PR (3%) was observed (95% CI, .1% to 15.8%). Adverse effects included leukopenia (23%), nausea and vomiting (73%), and mild azotemia (42%). No patients experienced life threatening toxicity. Cisplatin has definite activity when given at the dose and schedule that we tested for patients with mixed mesodermal sarcomas who have not received prior chemotherapy, but has little activity in patients with leiomyosarcoma. PMID- 1941055 TI - Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer. AB - In a previous study (J Clin Oncol 7:1407-1417, 1989), we identified two dosage administration schedules of fluorouracil (5FU) combined with leucovorin that were superior to single-agent 5FU for the treatment of advanced colorectal cancer. In this same study, a regimen of 5FU plus high-dose methotrexate (MTX) demonstrated a suggestive advantage over 5FU alone. To permit a more definitive comparison, we have extended our evaluation of these three regimens to involve an additional 259 patients. In all, 457 patients with advanced colorectal cancer were randomly assigned to one of the following regimens: 5FU plus low-dose leucovorin, 5FU plus high-dose leucovorin, or 5FU plus high-dose MTX with leucovorin rescue. We have found that each of the 5FU/leucovorin regimens demonstrates a significant (P less than or equal to .01) advantage over 5FU plus high-dose MTX for objective tumor response and interval to tumor progression. Moreover, 5FU plus low-dose leucovorin confers a significant survival benefit (P less than or equal to .01) compared with 5FU plus high-dose MTX. The 5FU plus high-dose leucovorin regimen shows a survival benefit only in unadjusted analyses (P = .04), but this difference is not significant when adjusted for imbalances in prognostic variables (P = .44). Evaluation of the two 5FU/leucovorin regimens rules out a 10% decrease in death rate for the high-dose leucovorin regimen compared with the low-dose leucovorin regimen (P less than .05). The regimen of 5FU plus low-dose leucovorin has now been shown to offer a statistically significant survival advantage versus 5FU alone and versus 5FU plus high-dose MTX, a regimen that had shown promise in earlier trials. These data confirm the efficacy of leucovorin combined with 5FU in patients with advanced colorectal cancer and establish that it is not necessary to use high doses of leucovorin to achieve these results. PMID- 1941056 TI - CNS involvement in small noncleaved-cell lymphoma: is CNS disease per se a poor prognostic sign? AB - Of 120 patients with small noncleaved-cell lymphoma who were entered sequentially on four National Cancer Institute (NCI) protocols, 29 (24%) had CNS involvement at some time in their clinical course. Seventeen had initial CNS involvement, and 12 developed CNS involvement at the time of first relapse. All 29 patients had extensive disease at presentation. The median serum lactate dehydrogenase (LDH) levels at presentation were 1,150 IU/L for patients with initial CNS involvement and 1,083 IU/L for patients with CNS involvement at relapse. CNS disease was significantly associated with serum LDH levels (P less than .0001), bone marrow involvement (P less than .0001), and jaw involvement (P = .018), but not involvement of the abdomen. There were nine long-term survivors among the 29 patients (31%). CNS disease did not appear to confer a worse prognosis on these patients than on patients without CNS involvement who had similar degrees of serum LDH elevation or who had bone marrow involvement, suggesting that extensive disease rather than CNS involvement was responsible for the poor prognosis. Event free survival for patients with serum LDH levels above 500 IU/L was not different whether CNS disease was present or not (P = .29), nor was event-free survival different for patients with stage IV disease, whether CNS disease was present or not (P = .92). Although some patients had CNS radiation, there was no evidence that this was of therapeutic benefit. Intrathecal (IT) chemoprophylaxis effectively prevented spread to the CNS in patients without initial CNS involvement. Five of 18 patients (28%) who received no IT prophylaxis had CNS relapse (four isolated to the CNS), but only seven of the 85 patients (8%) who received IT prophylaxis had CNS relapse (two isolated to the CNS). The differences in overall and isolated CNS relapse rates were statistically significant (P = .034 and P = .008, respectively). PMID- 1941057 TI - Combined modality therapy of Hodgkin's disease: 10-year results of National Cancer Institute of Canada Clinical Trials Group multicenter clinical trial. AB - The purpose of this study was to compare four methods of treatment for stage III IV Hodgkin's disease. Between January 1972 and September 1976, 266 patients with stage IIIB, IVA, and IVB Hodgkin's disease from 21 cancer treatment centers across Canada were registered as eligible; 40 were found to be ineligible. Of the 226 remaining patients, only seven were followed for less than 10 years. All patients received three courses of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, which induced a complete response (CR) in 36%; an additional 42% obtained adequate disease control. Patients were randomly assigned to (1) treatment with radiation to the abdomen and mantle (group AX3, 62 patients) or (2) continue their treatment with an additional three courses of MOPP (group A, 105 patients). For the A group, a second randomization took place 3 months later (regardless of status at that time) to (1) no further treatment (AC6, 23 patients), (2) radiotherapy to the abdomen and mantle (AX6, 48 patients), or (3) maintenance chemotherapy at 3-month intervals for 1 year (AC10, 26 patients). The survival of AX3 patients was somewhat better than for the A group, but the difference was not significant (P = .0565). However, there was a significant interaction (P = .0029) between age and treatment, so that among patients less than 30 years of age, the survival of the A group was better, whereas for older patients, treatment with AX3 resulted in improved survival. Age itself remained a significant prognostic factor for survival after controlling for the amount of radiotherapy delivered to the abdomen and the dose intensity of vincristine for the first three courses of chemotherapy. The addition of radiation therapy to MOPP significantly reduced the frequency of nodal relapses. These results suggest that combined modality therapy may be beneficial for some patients with Hodgkin's disease and that age must be carefully considered in interpreting the results of clinical trials in Hodgkin's disease. PMID- 1941058 TI - Cutaneous lymphomas other than mycosis fungoides: follow-up study of 52 patients. AB - Cutaneous lymphomas other than mycosis fungoides (MF) represent a rare and heterogeneous group of lymphomas. Their clinical behavior remains largely unknown. In this study, the clinical and immunohistologic characteristics and follow-up data of 52 well-documented cases of cutaneous lymphomas other than MF, presenting with initial cutaneous lesions, were reviewed. Twenty-seven patients presented with skin disease alone (stage IE), and 25 patients had concurrent cutaneous and extracutaneous disease (stage IV). The tumors were grouped into high-grade lymphomas (HGLs; 21%), intermediate-grade lymphomas (IGLs; 58%), and low-grade lymphomas (LGLs; 21%). A B-cell phenotype was most often expressed by cutaneous lymphomas (73%), particularly by stage IE lymphomas (85%). Among 13 cases of T-cell lymphomas, loss of one of the pan-T-cell antigens was detected in all cases but one. The clinical course of cutaneous lymphoma was closely dependent on stage and histologic subtype but not on T-cell or B-cell phenotype. Of 20 patients with stage IV HGL or IGL, 13 were treated by polychemotherapy with curative potential. Their median survival was 37 months. Fourteen patients with stage IE HGL or IGL were treated by radiotherapy alone. Nine patients (69%) relapsed within 2 years posttreatment. Seven of them relapsed in the skin outside the initial site involved, suggesting that radiotherapy alone is not an adequate treatment for these patients. Preliminary results concerning seven other patients with stage IE IGL or HGL treated by an initial third-generation polychemotherapy regimen are presented. PMID- 1941059 TI - The effects of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphocytic leukemia: a prospective randomized clinical trial by Cancer and Leukemia Group B. AB - Cancer and Leukemia Group B undertook a randomized trial of intensification treatment in adults aged 15 to 79 years with acute lymphocytic leukemia (ALL) in complete remission (CR). Daunorubicin (DNR), prednisone, vincristine (VCR), intrathecal (IT) methotrexate (MTX), and asparaginase produced 177 CRs in 277 patients. One hundred fifty-one patients were randomly assigned to receive treatment as follows: 74 received intensive cytarabine and DNR, and 77 received cycles of mercaptopurine (6-MP) and MTX, followed by 6MP, MTX, VCR, and prednisone for 3 years in all. One hundred twelve patients received CNS prophylaxis. Intensification produced major myelosuppression but did not improve remission duration (median, 21 months). Of the 151 patients with CRs who entered the intensification phase, 29% remain in continuous CR (43 to 117 months); in 19 patients, CRs have lasted for longer than 7 years. No relapses occurred after 60 months. Median survival from the time of randomization was 30 months. Those under 30 years of age responded more frequently, with longer CR and survival. While 53% of those aged 15 to 19 years remain in continuous CR, 92% of patients over 59 years have relapsed. The presence of a myeloid antigen on the leukemic cells was adversely prognostic for CR achievement and for survival. Pretreatment WBC and platelet levels independently affected CR duration and survival. Early M1 marrow development presaged longer remissions. CNS relapse occurred in 47 of 256 patients with normal CSF before treatment, in 29 before CNS prophylaxis. CNS disease occurred after CNS prophylaxis in 18 patients: 13 of 61 who had received standard premaintenance and five of 51 who received intensification. No advantage in CR duration or survival resulted from intensive treatment with DNR and cytarabine following induction of CR. PMID- 1941060 TI - Mesna versus hyperhydration for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation. AB - Hemorrhagic cystitis is a major complication of high-dose cyclophosphamide therapy used in preparation for allogeneic or autologous bone marrow transplantation. Although previous reports had suggested that the sulfhydryl containing compound mesna might be superior to forced diuresis in preventing hemorrhagic cystitis, there were concerns about the effect of mesna on engraftment in these studies. To address these concerns, 100 patients were randomized to receive mesna or forced saline diuresis while undergoing bone marrow transplant conditioning with regimens that included high-dose cyclophosphamide. To try to minimize the likelihood of graft rejection, patients who were being transplanted with cyclophosphamide as a sole agent were excluded from the study. After randomization and administration of therapy, patients were monitored by microscopic and dip-stick urinalyses; they were also followed for effects of therapy on engraftment. The incidence of consistent or severe hematuria was 33% in the mesna arm and 20% in the hyperhydration arm (P = .31). Severe bleeding occurred in 12.5% of mesna patients and 7.5% of hyperhydration patients (P = .71). No unexpected toxicities were encountered, and engraftment times did not differ. Based on this randomized trial of 100 patients, we conclude that mesna and hyperhydration are equally effective in preventing cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation patients. PMID- 1941061 TI - Treatment of chemotherapy-induced anemia with recombinant human erythropoietin in cancer patients. AB - Thirty patients with chemotherapy-induced anemia were treated with recombinant human erythropoietin for 4 weeks. In this dose-escalation study, cohorts of five to eight patients were treated per dose level. The doses of erythropoietin were 25, 50, 100, 200, or 300 IU/kg/d given intravenously for 5 days each week. Of 30 patients, 15 (50%) had a greater than 10% increase of their hemoglobin (Hb) values and were considered responders. At the two highest dose levels, 11 of 13 patients (85%) responded. In the 15 responding patients, the mean Hb level increased by 1.7 g/dL from baseline compared with an average decrease of 1.5 g/dL in the previous cycles of chemotherapy without erythropoietin administration. Recombinant human erythropoietin is effective in ameliorating chemotherapy induced anemia when administered in adequate doses. PMID- 1941062 TI - Pharmacokinetic and pharmacodynamic analysis of fluorouracil during 72-hour continuous infusion with and without dipyridamole. AB - During a phase I trial of 3-day simultaneous continuous intravenous infusions of varying doses of fluorouracil (5FUra) and 7.7 mg/kg/d of dipyridamole, we examined the relationships between 5FUra dose and steady-state plasma concentration (Css) and the percentage reduction in WBCs, as well as the percentage frequency of stomatitis. The 5FUra was administered at doses ranging from 185 mg/m2/d times three to 3,600 mg/m2/d times three. In 42 patients, 86 cycles of 5FUra plus dipyridamole and 28 cycles of 5FUra alone were analyzed. The Css of 5FUra varied even within the same dose level. When patients receiving the same 5FUra dose were considered, the interpatient coefficient of variation of 5FUra Css in cycles of 5FUra plus dipyridamole was 23% +/- 4.2%. For courses of 5FUra alone, the coefficient of variation of 5FUra was 15.6% +/- 6.5%. When the occurrence of any degree of stomatitis was related to the Css 5FUra, with patients grouped in cohorts of 2-mumol/L increments, the following equations accurately described the frequency of stomatitis: for 5FUra plus dipyridamole, percentage frequency of stomatitis = 100(1-e-0.114Css), r2 = 0.88; for 5FUra alone, percentage frequency stomatitis = 100(1-e0.122Css), r2 = 0.80. When 5FUra dose was substituted for Css, these relationships were as follows: percentage frequency of stomatitis = 100(1-e-0.00031 [dose]), r2 = 0.85; and percentage frequency of stomatitis = 100(1-e-0.00051 [dose]), r2 = 0.80. When the relationship between the percentage reduction in WBC and Css 5FUra was examined, statistically significant relationships were also apparent: for 5FUra plus dipyridamole, percentage reduction in WBC = 100(1-e-0.085Css), r2 = 0.46; for 5FUra alone, percentage reduction in WBC = 100(1-e-0.060Css), r2 = 0.61. When 5FUra dose was substituted for Css, these relatinships were as follows: percentage reduction in WBC = 100(1-e-0.00023 [dose]), r2 = 0.40; percentage reduction in WBC = 100(1-e-0.00024 [dose]), r2 = 0.65. The relationship between either Css 5FUra or dose 5FUra and either stomatitis or myelosuppression were also well described by the modified Hill equation (J Theor Biol 20:171-201, 1968). These analyses indicate that it should be possible to develop therapeutic regimens wherein 5FUra is administered to achieve a targeted Css determined by the risk and severity of toxicity deemed acceptable. PMID- 1941063 TI - The calculation of actual or received dose intensity: a comparison of published methods. AB - Two recent reports of the same combination chemotherapy program, cyclophosphamide, doxorubicin, etoposide, methotrexate, cytarabine, vincristine, bleomycin, and prednisone (ProMACE-CytaBOM), in similar subsets of patients with advanced-stage aggressive-histology lymphoma used two different methods to report the actual dose-intensity (DI) data. One method treats DI as a property of a particular cycle of treatment within the entire population that received that cycle. The other treats DI as a characteristic of a particular patient's entire treatment course. We have applied both methods to the same set of data and provide evidence that the latter method is preferable for at least two reasons: (1) it more accurately reflects actual DI by clearly incorporating the duration of the actual treatment course and, thus, can be used to compare the administration of same or related regimens to distinct patient populations; and (2) it allows assignment of a numerical value to an individual patient's treatment course or a group of patients' treatment courses such that DI can be examined for its impact on treatment outcome just like any other prognostic factor. The observed differences in treatment outcome between the Southwest Oncology Group (SWOG) and National Cancer Institute (NCI) studies are not clearly related to differences in distribution of clinical prognostic factors in the two study populations. The differences in methods of reporting DI prohibit evaluation of the influence of dose-related variables on outcome in the two studies. Adoption of a standard method of calculating and reporting DI data would facilitate evaluation of the prognostic significance of DI. PMID- 1941064 TI - Levamisole: known effects on the immune system, clinical results, and future applications to the treatment of cancer. AB - Levamisole has been used in a wide array of clinical research and treatment settings over the past two decades, ranging from such diseases as helminthic infestations to various autoimmune diseases. Numerous preclinical evaluations and clinical trials with levamisole in the cancer arena have been sponsored by the National Cancer Institute and other agencies worldwide with the hopes of demonstrating anticancer activity. Trials in advanced breast cancer, lung cancer, colorectal cancer, melanoma, and lymphoproliferative diseases have generally been negative or inconclusive. However, there is some indication that levamisole may be useful by itself as an adjuvant therapy for resected melanoma; recently it has been shown to be effective in combination with fluorouracil (5-FU) as adjuvant therapy for tumor-node-metastasis (TNM) stage III (Dukes' C) colon carcinoma. In the aggregate, the past 20 years of clinical experience with levamisole has resulted in as many questions as answers. However, further testing of the anticancer activity of levamisole can be expected in clinical research trials over the next few years. Hopefully, these future trials will include studies of the mechanisms of action of this agent. PMID- 1941065 TI - Oncologists' reluctance to accrue patients onto clinical trials: an Illinois Cancer Center study. AB - Clinical trials are recognized as the standard of care for the cancer patient, and the randomized, controlled trial represents the most definitive method to determine the effectiveness or ineffectiveness of a cancer treatment. However, less than 3% of all eligible patients enter a clinical trial. Of the 437 physician members of the Illinois Cancer Center (ICC), 244 responded to a survey designed to determine factors that present a significant barrier to entering patients on clinical trials. Rigid protocol design was the primary deterrent to accrual, especially for medical oncologists. Surgeons, radiation oncologists, and medical oncologists differed with respect to several factors, including willingness to seek a clinical trial, tendency to treat patients off study, quality-of-life issues, and the belief that trials were too excessive in time commitment (P less than .05). Compared with hospital-based physicians, community oncologists had fewer patients on trial, were more likely to enter patients on the basis of age, and were more concerned about aspects of informed consent and the financial burden of a trial (P less than .01). One third of the physicians never pursued a clinical trial because of conflict with the priorities of individual care and excessive follow-up time. Fourteen percent indicated that they discouraged patients from participating in a clinical trial due to the risk of a patient receiving a placebo and patient follow-up requirements (P less than .05). Subgroups of physicians differ in their reluctance to accrue patients, and there are clusters of beliefs expressed by physicians concerning their clinical trial activity. Current conduct of clinical trials needs to be reassessed, and intervention studies are required to determine the best methodology to alter physician reluctance to pursue clinical trials. PMID- 1941066 TI - Fluorouracil/leucovorin study update. PMID- 1941067 TI - Role of radiotherapy in neuroblastoma. PMID- 1941068 TI - Chemotherapy in advanced gastric carcinoma. PMID- 1941069 TI - Hepatic resection in colorectal carcinoma and survival. PMID- 1941071 TI - Functional specificity of a long-range horizontal connection in cat visual cortex: a cross-correlation study. AB - Anatomical investigations of the visual cortex revealed a regular set of interlaminar connections and long-range horizontal connections. An important component of the intrinsic cortical circuit is the projection from layer 5 to layer 6 over long horizontal distances. Previous work has shown that when layer 5 is locally inactivated, layer 6 cells lose their response in a segment of their receptive fields corresponding to the blocked area in layer 5. It has therefore been proposed that the long receptive fields characteristic of layer 6 cells might be generated by concatenating layer 5 cells with similar orientation preferences. In the present study, we used cross-correlation analysis to examine both source and target cells of the interlaminar connection from layer 5 to layer 6. We found correlated firing between cells separated by up to 4.2 mm, the longest horizontal distance studied. The occurrence of correlated firing depended on the functional properties and on the topographic position of the cells in layer 5 and layer 6. Interactions were only observed if the cells had matching orientation tuning and similar eye preference and if the layer 5 cells lay within the summation area of the layer 6 cells. Both simple and complex cells in layer 6 fired in synchrony with layer 5 cells. In layer 5, mainly standard complex cells, but very few special complex cells, participated in correlated firing with layer 6 cells. These results suggest that cells in layer 6 receive their input from cooriented, coaxially aligned standard complex cells in layer 5. This topographic arrangement and the length summation properties of standard complex cells in layer 5 are well suited to generate long receptive fields in layer 6. Thus, our experiments provide evidence for the functional specialization of a particular component of cortical circuitry. PMID- 1941070 TI - Muller cells are a preferred substrate for in vitro neurite extension by rod photoreceptor cells. AB - To define the factors important in photoreceptor cell morphogenesis, we have examined the ability of rods to extend neurites in vitro. Retinas from neonatal rats were dissociated and plated onto substrate-bound extracellular matrix (ECM) components or cell monolayers. When rods, identified with monoclonal antibodies to opsin, were in contact exclusively with purified ECM (e.g., laminin, fibronectin, type I collagen, or Matrigel), neurite outgrowth was extremely limited. By contrast, rods extended long neurites on Muller cells. Retinal or brain astrocytes, endothelial cells, 3T3 fibroblasts, or other retinal neurons were less supportive of rod process outgrowth. These data demonstrate regional specificity in the promotion of neurite outgrowth by glia and suggest that not all neurons within the retina require the same morphogenic factors. PMID- 1941072 TI - Developmental changes in the membrane current pattern, K+ buffer capacity, and morphology of glial cells in the corpus callosum slice. AB - Recent studies indicated that glial cells in tissue culture can express a variety of different voltage-gated channels, while little is known about the presence of such channels in glial cells in vivo. We used a mouse corpus callosum slice preparation, in which after postnatal day 5 (P5) more than 99% of all perikarya belong to glial cells (Sturrock, 1976), to study the current patterns of glial cells during their development in situ. We combined the patch-clamp technique with intracellular labeling using Lucifer yellow (LY) and subsequent ultrastructural characterization. In slices of mice from P6 to P8, we predominantly found cells expressing delayed-rectifier K+ currents. They were similar to those described for cultured glial precursor cells (Sontheimer et al., 1989). A-type K+ currents or Na+ currents were not or only rarely observed, in contrast to cultured glial precursors. LY labeling revealed that numerous thin processes extended radially from the perikaryon of these cells, and ultrastructural observations suggested that they resemble immature glial cells. In slices of older mice (P10-13), when myelination of the corpus callosum has already commenced, many cells were characterized by an almost linear current voltage relationship. This current pattern was similar to cultured oligodendrocytes (Sontheimer et al., 1989). Most processes of LY-filled cells with such a current profile extended parallel to each other. Electron microscopy showed that these processes surround thick, unmyelinated axons. We suggest that cells with oligodendrocyte-type electrophysiology are promyelinating oligodendrocytes. In contrast to cultured oligodendrocytes, membrane currents of promyelinating oligodendrocytes in the slice decayed during the voltage command. This decay was due not to inactivation, but to a marked change in the potassium equilibrium potential within the voltage jump. This implies that, in the more mature corpus callosum, small membrane polarizations in a physiological range can lead to extensive changes in the K+ gradient across the glial membrane within a few milliseconds. PMID- 1941073 TI - Target-dependent hormonal control of neuron size in the rat spinal nucleus of the bulbocavernosus. AB - The spinal nucleus of the bulbocavernosus (SNB) in the rat is a cluster of sexually dimorphic motoneurons that innervate perineal muscles. In adult male rats, the size of SNB neurons is reduced following castration, and this effect is reversed by treatment with testosterone. However, androgen receptors are present in the perineal muscles as well as in SNB neurons. Therefore, it is not clear whether the neuronal size is regulated by direct action of the hormone on SNB neurons or by a target-derived factor that may be controlled via hormonal action on the innervated muscle. To address this question, the peripheral (pudendal) nerve of SNB neurons on one side was cut and united to the grafted soleus muscle, which lacks androgen sensitivity. On the control side, the pudendal nerve was similarly cut but was allowed to reinnervate the perineal muscles. The size of SNB neurons was measured on both sides after a postoperative period of 10 weeks, during which the animal had been castrated or treated with testosterone after castration. The size of SNB neurons that had reinnervated perineal muscles was reduced following castration and enlarged by testosterone treatment. In contrast, the size of SNB neurons that had innervated the soleus muscle remained unaltered in response to testosterone manipulation. It is concluded that hormonal regulation of the size of SNB neurons in adult rats is mediated by their target muscles. PMID- 1941074 TI - The neurotrophic effects of fibroblast growth factors on dopaminergic neurons in vitro are mediated by mesencephalic glia. AB - Neurotrophic support is generally believed to result from a direct action of growth factors on developing neurons. However, there is increasing evidence that growth factors can indirectly affect neuronal development by glial-mediated processes. To investigate a possible role of glia in mediating neurotrophic effects on dopaminergic neurons, four purified growth factors were screened for dual effects on the survival and differentiation of dopaminergic neurons and on the proliferation of mesencephalic glial cells in vitro. Dissociated embryonic day 14.5 rat mesencephalon was grown at low cell density without serum, conditions under which both glial growth and neuronal survival are not optimal. Treatment of these cultures with acidic fibroblast growth factor (aFGF) or basic fibroblast growth factor (bFGF) increased the number of surviving tyrosine hydroxylase-immunoreactive (TH-IR) neurons by 90-110% [corrected] at 8 d in vitro in a dose-dependent manner. The effects of these factors were not additive. High affinity dopamine uptake was increased by bFGF, but not by aFGF. Length of TH-IR neurites was not affected by either aFGF or bFGF. Both growth factors induced proliferation of mesencephalic astrocytes as demonstrated by autoradiographic labeling with 3H-thymidine combined with immunocytochemistry for glial fibrillary acidic protein (GFAP). In contrast, platelet-derived growth factor (PDGF) and interleukin-1 had no effect on the survival or differentiation of dopaminergic neurons or the proliferation of mesencephalic astrocytes. Inhibition of glial proliferation abolished the neurotrophic effects exerted by aFGF or bFGF on dopaminergic neurons. Moreover, conditioned medium derived from mesencephalic glial cultures replated in the virtual absence of neurons also contained neurotrophic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941075 TI - Voltage-sensitive potassium channels in Drosophila photoreceptors. AB - A preparation of dissociated Drosophila ommatidia is described that allows single channel and whole-cell patch-clamp analysis of currents in identified sensory neurons. Three distinct classes of voltage-sensitive potassium conductances are characterized; all were detected in distal parts of ommatidia from sevenless mutants and hence in one cell class (R1-6 photoreceptors). Rapidly inactivating A channels (IA), coded by the Shaker gene, were isolated in multichannel patches from adult flies. While showing similar kinetics to muscle A-channels, they differ from previously characterized wild-type Shaker channels in having a much more negative voltage operating range, being half-inactivated at approximately 70 mV. Two delayed rectifier conductances were characterized in whole-cell recordings from pupal photoreceptors. The most commonly encountered class (IKs) is similar to previously reported delayed rectifier conductances in Drosophila. It inactivates slowly (time constant, approximately 500 msec) and is half inactivated at approximately -40 mV. A more rapidly inactivating delayed rectifier (IKf) was detected in approximately 30% of cells; it is half inactivated at approximately -80 mV. Both IKs and IKf are blocked by 100 microM quinidine. Neither are greatly affected by 4-aminopyridine, which blocks IA at 1 5 mM. None of the three conductances was calcium dependent, nor were they obviously affected by the eag mutation, which affects K channels in muscle. The developmental profile of the channels is the inverse of that described in muscle. Both IKs and IKf are present at the earliest pupal stages examined (approximately 60 hr), but IA was only first detected at approximately 76 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941076 TI - Reversible inhibition of voltage-dependent outer hair cell motility and capacitance. AB - Outer hair cells (OHC) from the organ of Corti are capable of fast voltage induced length changes (Santos-Sacchi and Dilger, 1988), suggesting that an associated voltage sensor should reside in the OHC plasma membrane. Voltage dependent mechanical responses and nonlinear charge movement of isolated OHCs from the guinea pig were analyzed using the whole-cell voltage-clamp technique. Ionic currents in the cells were blocked. Nonlinear voltage-dependent charge movement or, correspondingly, voltage-dependent capacitance was measured with step or AC analysis. OHC movements were measured either from video or using a differential photodiode technique. Maximum charge movements up to 2.5 pC were measured in OHCs from the low-frequency region of the cochlea. Both AC and step analyses indicated a peak nonlinear capacitance of 16-17 pF. The voltage dependence was fit to a Boltzmann relation with the step analysis indicating a maximum nonlinear capacitance at -23 mV step potential from a holding potential of about -120 mV, and AC analysis indicating a maximum at a holding potential near -40 mV. AC analysis probably provides a more accurate evaluation of voltage dependence. Measures of OHC motility magnitude versus voltage follow the nonlinear capacitance-voltage function obtained from AC measures. Treatment of the cells with gadolinium ions (0.5-1 mM) blocked OHC motility. This treatment also produced a shift of the nonlinear capacitance function along the voltage axis in the depolarizing direction, which can be explained by membrane surface charge screening. However, maximum capacitance was reduced as well and may correspond to the reduction or abolition of OHC motility in response to gadolinium treatment. Gadolinium effects were reversible. Nonlinear capacitance is not a function of membrane deformation due to length changes, since removal of OHC cytosol via the patch pipette abolished longitudinal movement but did not reduce nonlinear charge movement. It is interesting to note that the nonlinear capacitance will dynamically influence the time constant of the OHC during acoustically evoked receptor potential generation. PMID- 1941078 TI - Neurofilament redistribution in transected nerves: evidence for bidirectional transport of neurofilaments. AB - Nerve fibers of the C57BL/6/Ola mouse exhibit very slow Wallerian degeneration following axotomy, thus allowing prolonged observation of mammalian axons separated from their cell bodies. The present study utilized teased-fiber preparations, silver histochemistry, immunocytochemistry, and electron microscopy to examine the distribution of axonal components in the distal stumps of axotomized sciatic nerves in C57BL/6/Ola mice. In examining nerve segments at varying intervals after nerve transection, we found no evidence of proximal-to distal "emptying out" of the cytoskeleton, as would be predicted if the cytoskeleton in these transected nerves were undergoing anterograde transport as an assembled structure. Instead, we observed a gradual redistribution of cytoskeletal constituents over time, dominated by the progressive accumulation of neurofilaments at the severed ends of axons. In particular, there were massive accumulations at the proximal ends of the distal stumps. These results strongly suggest that, at least in transected nerve fibers, neurofilaments can be transported bidirectionally. PMID- 1941077 TI - Ciliary neurotrophic factor enhances neuronal survival in embryonic rat hippocampal cultures. AB - First described as a survival factor for chick ciliary ganglion neurons, ciliary neurotrophic factor (CNTF) has recently been shown to promote survival of chick embryo motor neurons. We now report neurotrophic effects of CNTF toward three populations of rat hippocampal neurons, the first demonstration of effects of CNTF upon rodent CNS neurons in culture. CNTF elicited an increase in the neurofilament content of hippocampal cultures prepared from embryonic day 18 (E18) rat brain. This was accompanied by increases of 2-, 28-, and 3-fold in the number of GABAergic, cholinergic, and calbindin-immunopositive cells, respectively. CNTF totally prevented the 67% loss of GABAergic neurons that occurred in control cultures over 8 d. CNTF also increased high-affinity GABA uptake and glutamic acid decarboxylase activity. Effects of CNTF were in all cases dose dependent, with maximal stimulation at approximately 100 pg/ml. When addition was delayed for 3 d, CNTF failed to elicit increases either in the number of cholinergic neurons or in GABA uptake. PMID- 1941079 TI - Tuning of spinal networks to frequency components of spike trains in individual afferents. AB - Cord dorsum potentials (CDPs) evoked by primary afferent fiber stimulation reflect the response of postsynaptic dorsal horn neurons. The properties of these CDPs have been shown to vary in accordance with the type of primary afferent fiber stimulated. The purpose of the present study was to determine the relationships between frequency modulation of the afferent input trains, the amplitude modulation of the evoked CDPs, and the type of primary afferent stimulated. The somata of individual primary afferent fibers were impaled in the L7 dorsal root ganglion of alpha-chloralose-anesthetized cats. Action potentials (APs) were evoked in single identified afferents via the intracellular microelectrode while simultaneously recording the response of dorsal horn neurons as CDPs, or activity of individual target interneurons recorded extracellularly or intracellularly. APs were evoked in afferents using temporal patterns identical to the responses of selected afferents to natural stimulation of their receptive fields. Two such physiologically realistic trains, one recorded from a hair follicle and the other from a slowly adapting type 1 receptor, were chosen as standard test trains. Modulation of CDP amplitude in response to this frequency-modulated afferent activity varied according to the type of peripheral mechanoreceptor innervated. Dorsal horn networks driven by A beta afferents innervating hair follicles, rapidly adapting pad (Krause end bulb), and field receptors seemed "tuned" to amplify the onset of activity in single afferents. Networks driven by afferents innervating down hair follicles and pacinian corpuscles required more high-frequency activity to elicit their peak response. Dorsal horn networks driven by afferents innervating slowly adapting receptors including high-threshold mechanoreceptors exhibited some sensitivity to the instantaneous frequency, but in general they reproduced the activity in the afferent fiber much more faithfully. Responses of synaptically coupled dorsal horn neurons belonging to either hair follicle or SA1 fiber-driven networks to frequency-modulated input were in agreement with the CDP results, confirming that CDP amplitude modulation is a true reflection of EPSP amplitude modulation in at least a subset of dorsal horn neurons comprising the network. PMID- 1941080 TI - Network modulation of a slow intrinsic oscillation of cat thalamocortical neurons implicated in sleep delta waves: cortically induced synchronization and brainstem cholinergic suppression. AB - A slow (0.5-4 Hz) oscillation of thalamic neurons was recently described and attributed to the interplay of two intrinsic currents. In this study, we investigated the network modulation of this intrinsic thalamic oscillation within the frequency range of EEG sleep delta-waves. We performed intracellular and extracellular recordings of antidromically identified thalamocortical cells (n = 305) in sensory, motor, associational, and intralaminar nuclei of anesthetized cats. At the resting membrane potential, Vm (-60.3 +/- 0.4 mV, mean +/- SE), cortical stimulation induced spindle-like oscillations (7-14 Hz), whereas at Vm more negative than -65 mV the same stimuli triggered an oscillation within the EEG delta-frequency (0.5-4 Hz), consisting of low-threshold spikes (LTSs) followed by after hyperpolarizing potentials (AHPs). The LTS-AHP sequences outlasted cortical stimuli as a self-sustained rhythmicity at 1-2 Hz. Corticothalamic stimuli were able to transform subthreshold slow (0.5-4 Hz) oscillations, occurring spontaneously at Vm more negative than -65 mV, into rhythmic LTSs crowned by bursts of Na+ spikes that persisted for 10-20 sec after cessation of cortical volleys. Cortical volleys also revived a hyperpolarization activated slow oscillation when it dampened after a few cycles. Auto- and crosscorrelograms of neuronal pairs revealed that unrelated cells became synchronized after a series of corticothalamic stimuli, with both neurons displaying rhythmic (1-2 Hz) bursts or spike trains. Since delta-thalamic oscillations, prevailing during late sleep stages, are triggered at more negative Vm than spindles characterizing the early sleep stage, we postulate a progressive hyperpolarization of thalamocortical neurons with the deepening of the behavioral state of EEG-synchronized sleep. In view of the evidence that cortical-elicited slow oscillations depend on synaptically induced hyperpolarization of thalamocortical cells, we propose that the potentiating influence of the corticothalamic input results from the engagement of two GABAergic thalamic cell classes, reticular and local-circuit neurons. The thalamocorticothalamic loop would transfer the spike bursts of thalamic oscillating cells to cortical targets, which in turn would reinforce the oscillation by direct pathways and/or indirect projections relayed by reticular and local-circuit thalamic cells. Stimulation of mesopontine cholinergic [peribrachial (PB) and laterodorsal tegmental (LDT)] nuclei in monoamine-depleted animals had an effect that was opposite to that exerted by corticothalamic volleys. PB/LDT stimulation reduced or suppressed the slow (1-4 Hz) oscillatory bursts of high-frequency spikes in thalamic cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1941082 TI - Regulation of neuropeptide stoichiometry in neurosecretory cells. AB - Peptidergic neurons and neurosecretory cells often contain multiple peptides, where they may be present in characteristic ratios. In this article, we describe how a set of five colocalized and coreleased peptides, two adipokinetic hormones (AKH I and AKH II), and three dimeric peptides (APRP 1, 2, and 3) are synthesized by the neurosecretory cells of the corpora cardiaca of the locust Schistocerca gregaria. We show that the five peptides are produced from two prohormones called pro-AKH I, or A-chain, and pro-AKH II, or B-chain. The amino acid sequences as determined by direct protein sequencing are given for both. Prior to processing, the two prohormones form the three possible dimers by the oxidation of the single cysteine residues found in each. The dimers, not the prohormones, are the direct precursors of the peptides. The dimeric precursors are called P1 (A-A), P2 (A-B), and P3 (B-B). Processing results in the generation of the two AKH peptides and the three dimers called adipokinetic hormone precursor-related peptides, or APRPs. Throughout postembryonic development, we show that the ratios of the AKHs and APRPs change dramatically and systematically. We show that these changes can be explained by the differential regulation of the synthesis of the two prohormones and their random association into dimers that are then completely processed. Regulation of peptide stoichiometry may expand the potential information content of the signals generated by multipeptide-producing neurons. PMID- 1941081 TI - Identification and localization of muscarinic acetylcholine receptor proteins in brain with subtype-specific antibodies. AB - mRNAs encoding five genetically distinct muscarinic ACh receptors are present in the CNS. Because of their pharmacological similarities, it has not been possible to detect the individual encoded proteins; thus, their physiological functions are not well defined. To characterize the family of proteins, a panel of subtype selective antibodies was generated against recombinant muscarinic receptor proteins and shown to bind specifically to each of the cloned receptors. Using immunoprecipitation, three receptor proteins (m1, m2, and m4) accounted for the vast majority of the total solubilized muscarinic binding sites in rat brain. These receptor subtypes had marked differences in regional and cellular localization as shown by immunocytochemistry. The m1-protein was present in cortex and striatum and was localized to cell bodies and neurites, consistent with its role as a major postsynaptic muscarinic receptor. The m2-receptor protein was abundant in basal forebrain, scattered striatal neurons, mesopontine tegmentum, and cranial motor nuclei; this distribution is similar to that of cholinergic neurons and suggests that m2 is an autoreceptor. However, m2 was also present in noncholinergic cortical and subcortical structures, providing evidence that this subtype may presynaptically modulate release of other neurotransmitters and/or function postsynaptically. The m4-receptor was enriched in neostriatum, olfactory tubercle, and islands of Calleja, indicating an important role in extrapyramidal function. These results clarify the roles of these genetically defined receptor proteins in cholinergic transmission in brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941083 TI - Membrane resealing in cultured rat septal neurons after neurite transection: evidence for enhancement by Ca(2+)-triggered protease activity and cytoskeletal disassembly. AB - Neurites of cultured septal neurons were transected with a laser under sterile conditions, and the subsequent membrane resealing was assayed using a dye exclusion method. In agreement with findings in other preparations, Ca2+ enhanced resealing: in normal culture medium the percentage of lesioned neurons that resealed within 20-30 min after transection increased with increasing bath [Ca2+] over the range 10(-7) to 2 x 10(-3) M; about 75% of cells resealed in 2 mM Ca2+. Mn2+ and Sr2+ also enhanced resealing, but Mg2+ inhibited it. The percentage of resealing neurons was sensitive to agents known to alter the stability of cytoskeletal components. Agents that tend to disassemble microtubules and/or neurofilaments (e.g., colchicine, low-ionic-strength media) strongly promoted resealing, whereas treatments that tend to stabilize microtubules (taxol, Mg2+) inhibited resealing. Addition of exogenous proteases (papain, trypsin, or dispase) enhanced resealing, whereas inhibitors of cysteine proteases (including a specific inhibitor of calpain, a Ca-activated neutral protease) strongly inhibited resealing. Calmodulin inhibitors inhibited resealing, consistent with reports that calmodulin facilitates calpain-mediated proteolysis of fodrin, a component of the cortical cytoskeleton. Based on these results, we hypothesize that one of the major mechanisms involved in resealing is activation of endogenous proteases by Ca2+ entry into the injured neurite. The resulting changes in the cellular cytoskeleton might promote fusion and resealing of the cut ends of the plasma membrane by enhancing membrane mobility and/or by removing structures that normally prevent membrane-membrane contact. PMID- 1941084 TI - Effects of monocular visual deprivation on geniculocortical innervation of area 18 in cat. AB - The effects of long-term monocular visual deprivation (MD) on the structure of the terminal arborizations of individual Y-type geniculocortical axons was studied in the cat's cortical area 18. Physiologically classified axons were filled with HRP by intracellular injection, and the three-dimensional distribution of the axons' terminal arborizations was quantified. Individual boutons observed at the light microscope (LM) level were verified as sites of synaptic contact by correlated light and electron microscopy (EM). Single boutons were serially sectioned and reconstructed for subsequent three-dimensional analysis. The arborizations of 17 Y-axons [6 normal (N), 6 nondeprived (ND), and 5 deprived (D)] were analyzed at the LM level, and 372 boutons (104 N, 129 ND, and 139 D) were fully reconstructed from serial sections for analysis at the EM level. MD leads to an expansion in the size of ND arborizations and a variable reduction in the size of the D arbors, which also have a higher bouton density than ND arborizations. ND axons form ectopic synapses, contacting proportionally more dendritic shafts than N or D boutons, and form more synapses per bouton, on average, than either N or D boutons. Compared to ND and N boutons, boutons of D axons are smaller, have fewer mitochondria, generally form synapses on a single target (usually dendritic spines), and occasionally make no synaptic contacts. The structural changes in the extent of individual axon arborizations may be the basis for change in ocular dominance column size with MD. However, the higher bouton density and variable effect on the extent of D axon arborization size suggest that considerable geniculocortical innervation from the deprived eye remains intact. The change in target preference for ND axons suggests that instead of a direct competition for postsynaptic sites by the developing geniculocortical axons innervated by the two retinas, the ND axon arborizations expand to invade synaptic space not normally occupied in such high proportion in the normal cortex. The severe changes in individual boutons following MD indicate that arborization size alone is not the only structural substrate underlying the altered responses of cortical neurons; changes in synaptic distribution onto target neurons may also play a role. PMID- 1941086 TI - Serotonergic facilitation of quantal release at central inhibitory synapses. AB - The teleost Mauthner (M)-cell is subjected to a powerful glycinergic inhibition that regulates its threshold for initiation of a vital escape reflex. The effects of 5-HT on this inhibition were studied in current- and voltage-clamp experiments because the M-cell and its afferents have a profuse serotonergic innervation, including axoaxonal contacts with terminals of the inhibitory interneurons. Local applications of the amine and/or of its uptake blockers markedly enhanced inhibitory currents evoked by synchronous activation of two identified presynaptic networks. In order to determine the site of this 5-HT action, we exploited the fact that in the M-cell, synaptic noise is predominantly inhibitory. Furthermore, its quantal components can be resolved providing a means to distinguish pre- and post-synaptic loci underlying variations in synaptic efficacy. As in other cell types, it consists of spontaneous exocytotic events and multiquantal responses triggered by action potentials in afferent neurons. 5 HT or its uptake blockers produced a long-lasting enhancement of this noise, manifested as a shift to the right of amplitude distribution histograms of the individual inhibitory postsynaptic currents (IPSCs) and an increase in the mean quantal content of noise. In contrast, the size of the miniature IPSC (mIPSCs) remained constant in these experiments and in another series where 5-HT was given in presence of TTX. In this case, the amine also increased the rate of occurrence of single quanta. Taken together, these data indicate that 5-HT acts presynaptically to increase the probability of evoked and spontaneous release of glycine. This conclusion was reinforced by evidence that the overall frequency of the responses in noise could be unaltered by 5-HT, indicating that the afferent firing pattern had remained constant. Extracellular recordings of the presynaptic volleys showed that action potentials were not prolonged and suggested that 5-HT closes K+ channels in the terminal membrane, leading to an increase of resistance and a larger depolarization in that region as a possible mechanism for the facilitation of release. While the enhancement of transmitter release persisted for 20 min or more, there was also a transient induction of a K+ inward rectifying current in the M-cell. These results indicate that 5-HT increases the efficacy of inhibitory synaptic transmission in the vertebrate CNS by a presynaptic action. PMID- 1941085 TI - Exposure to high-pH medium increases the incidence and extent of dye coupling between rat hippocampal CA1 pyramidal neurons in vitro. AB - Previous studies have demonstrated that dye coupling between neurons can be reduced by maneuvers that reduce intracellular pH. However, it is apparent that marked extracellular alkaline- as well as acid-going pH shifts can occur in the mammalian CNS. In light of the fact that an applied change in extracellular pH may produce a damped change in intracellular pH in the same direction, in this study we have examined the effects of exposure to high extracellular pH (achieved by raising [HCO3-] at a constant PCO2) on the incidence of Lucifer yellow dye coupling between CA1 pyramidal neurons in the rat hippocampal slice. Under standard conditions (pH 7.4), 44% of CA1 pyramidal neurons were dye-coupled, and the mean number of neurons stained per injection was 1.62. A marked increase in the incidence (88%) and extent (mean number of neurons stained per injection, 3.25) of dye coupling was observed during exposure to high-pH medium (pH 7.9). Under both standard and high-pH conditions, dye coupling was associated with the ability of CA1 pyramidal neurons to generate bursts of action potentials in response to intracellularly applied depolarizing current pulses. The results provide additional evidence that dye coupling between hippocampal pyramidal neurons may be modulated dynamically and may have implications for the genesis of synchronized epileptiform activity under alkalotic conditions. PMID- 1941087 TI - Distribution of Ca2+ and Na+ conductances during neuronal differentiation of chick DRG precursor cells. AB - The distribution of Ca2+ and Na+ conductances on neuronal precursor cells was investigated during differentiation. Ionic conductances on the soma or on the growth cone were isolated by superfusing all other parts of the cells with sucrose. Conductances on the neuritic shaft were detected as additional conductances after removing sucrose from the neuritis shaft. Neuronal precursor cells were isolated from chick dorsal root ganglia by selectively killing differentiated neurons. Cultured precursor cells differentiated into morphological and functional mature neurons. Functionally undifferentiated precursor cells (during the first 10 hr in culture) expressed only low-voltage activated (LVA) Ca2+ currents. High-voltage-activated (HVA) Ca2+ and Na+ currents appeared delayed after more than 10 hr in culture. Voltage-dependent conductances, if expressed by a cell, were present on all parts of the surface membrane at all stages of differentiation. LVA Ca2+ conductances were well represented on the growth cone as well as on the soma in functionally undifferentiated precursor cells. During differentiation of precursor cells, LVA Ca2+ and HVA Ca2+ as well as Na+ conductances were expressed on the somatic membrane, on the neuritic shaft, and on the growth cone. These results demonstrate the expression of Ca2+ channels on growth cones during differentiation. PMID- 1941088 TI - Patterns of activity coding discrimination of auditory stimuli differ between mid and posterolateral thalamus of cats. AB - The auditory function of units in the mid- (lateralis dorsalis and centrolateral nuclei) and posterolateral (lateralis posterior-pulvinar complex) thalamus of cats was assessed during performance of conditioned eye blink responses (CRs) elicited discriminatively by a forward-paired, 70 dB click conditioned stimulus (CS) as opposed to a backward-paired, 70 dB hiss discriminative stimulus (DS). Discharges in response to the CS or DS were found in over 40% of units tested in each area, with onset latencies as short as 28-32 msec in mid-thalamus and 14 msec in posterolateral thalamus. The results provide evidence that both mid- and posterolateral thalamic regions of cats contain sufficient numbers of auditory responsive neurons to be considered part of the auditory system functionally. Patterns of activity changed after conditioning discriminative responses to the click CS. In mid-thalamus, the ratio of CS-evoked activity to baseline activity increased relative to levels found before conditioning. This increase was attributable to an increase in the magnitude of response to the CS. In posterolateral thalamus, an increase in the signal: noise ratio of activity in response to the CS was also found after conditioning, but this increase depended in large part on a decrease in the rate of baseline firing. Posterolateral thalamic units had substantially higher mean rates of baseline firing than mid thalamic units before any conditioning sessions were begun.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941089 TI - Differential expression of synaptophysin and synaptoporin mRNAs in the postnatal rat central nervous system. AB - Synaptophysin and synaptoporin are two homologous integral membrane proteins of small synaptic vesicles. Here, the distribution of the corresponding transcripts in the CNS of the rat was investigated by in situ hybridization using sequence specific oligonucleotide probes. Synaptophysin mRNA was abundantly distributed through all major brain regions, whereas synaptoporin transcripts displayed a more restricted localization in telencephalic structures. Resolution at the cellular level disclosed a differential labeling of distinct cell types in different areas, suggesting that synaptophysin and synaptoporin are expressed by specific subpopulations of central neurons. Consistent with this conclusion, relative synaptoporin mRNA contents were found to vary between different brain regions during postnatal development, whereas synaptophysin transcripts showed a more uniform increase during the same period. PMID- 1941090 TI - The major 35S-methionine-labeled rapidly transported protein (superprotein) is identical to SNAP-25, a protein of synaptic terminals. AB - Superprotein is a rapidly axonally transported protein that is conspicuously labeled with 35S-methionine supplied to the cell bodies of retinal ganglion cells. Superprotein candidates are apparent among the rapidly transported proteins of many neurons from the CNS and PNS, including cranial, sympathetic, sensory, and motor neurons from mammals, fish, and amphibians. To determine the identity of Superprotein, we purified it from rabbit visual system and spinal cord and determined the amino acid sequence of seven of its tryptic peptides. The sequence shows that Superprotein is SNAP-25, a protein recently predicted from a cDNA sequence; SNAP-25 has been reported to be concentrated in the synaptic terminals of a selected population of CNS neurons. We measured the amount of radioactivity associated with Superprotein in tissue containing axons (optic tract) and synaptic terminals (superior collicules) of rabbit retinal ganglion cells. Labeled Superprotein disappeared from the superior colliculus more rapidly than another protein (synapsin I-like protein) that is concentrated in synaptic terminals. These results serve to unite the observations on the synthesis, distribution, metabolism, and axonal transport of Superprotein with observations of SNAP-25 and its mRNA. PMID- 1941091 TI - Does primate motion perception depend on the magnocellular pathway? AB - This study examined the importance of the primate magnocellular retinocortical pathway in the perception of moving stimuli. A portion of the magnocellular pathway was permanently and selectively interrupted by ibotenic acid injections in the LGN of macaque monkeys. We then tested contrast sensitivity for detecting moving stimuli, as well as two indices of motion perception, contrast sensitivity for opposite direction discrimination and speed difference thresholds, in the affected portion of the visual field. Magnocellular lesions greatly reduced detection contrast sensitivity at high temporal and low spatial frequencies and had a similar effect on contrast sensitivity for opposite direction discrimination under these same stimulus conditions. Consequently, opposite direction discriminations could be made at contrast threshold, suggesting that magnocellular lesions reduced the visibility of stimuli used to test direction perception, but did not act directly on direction perception. Magnocellular lesions also elevated speed difference thresholds under some stimulus conditions. However, this deficit was reduced or eliminated by raising the contrast of the test stimulus. Together, these findings suggest that magnocellular lesions reduce the visibility of stimuli used to test motion perception but that they do not appear to alter motion perception otherwise. PMID- 1941092 TI - The monaural nuclei of the lateral lemniscus in an echolocating bat: parallel pathways for analyzing temporal features of sound. AB - In echolocating bats, three cell groups in the lateral lemniscus are conspicuous for their large size and high degree of differentiation. These cell groups are the intermediate nucleus (INLL), columnar nucleus (VNLLc), and multipolar cell area (VNLLm). All receive projections from the contralateral cochlear nucleus. Previous anatomical studies suggest the hypothesis that these nuclei are important for analyzing the temporal structure of sound. To investigate this possibility, we recorded responses of single units in the INLL, VNLLc, and VNLLm of Eptesicus fuscus. The results show that each cytoarchitectural division contains a complete tonotopic representation. Certain response properties are common to all three nuclei. First, virtually all units are monaural. Second, all are broadly tuned to frequency; their average Q10dB value of 9.1 is considerably lower than values measured in the inferior colliculus of Eptesicus. Third, most units have little or no spontaneous activity. Fourth, all have short integration times, responding robustly to stimuli less than 5 msec in duration. The broad tuning, lack of spontaneous activity, and short integration time all make these neurons well suited for the accurate encoding of temporal information. Although there are many similarities, there are also important differences among nuclei. The clearest evidence of specialization is in VNLLc. Neurons here are more broadly tuned than those in INLL or VNLLm, have no spontaneous activity, and always respond with one spike per stimulus. The latency of the spike is precisely locked to the stimulus onset, with variability from trial to trial as low as 0.03 msec. In addition, the latency remains constant over large variations in frequency or intensity. In INLL and VNLLm, response patterns are about equally distributed between tonic, chopping, and phasic; there are no single-spike constant-latency responses of the type seen in VNLLc, although some choppers and pausers do respond with constant first-spike latency. The results indicate that VNLLc is specialized to encode very precisely the onset of sound; the other nuclei may encode ongoing properties of a sound. PMID- 1941093 TI - Guidance of callosal axons by radial glia in the developing cerebral cortex. AB - During development, columns of the mammalian cerebral cortex are formed by migration of neurons along fascicles of radial glia. Subsequently, axons of the corpus callosum connect reciprocal regions of each cerebral hemisphere. To determine whether the radial growth of callosal afferents through the developing cortex may be guided by particular cellular elements, we examined the ultrastructural relationship between callosal afferents and radial fibers in the early postnatal hamster sensorimotor cortex. Developing callosal axons and their growth cones were labeled with HRP injected into the cortex at 3 d postnatal when the growth cones have extended across the callosum and are just entering the contralateral cortex. An EM analysis of 30 HRP-labeled axons and their growth cones revealed that they extended upon fascicles of radial processes associated with migrating neurons. Reconstruction of seven of these growth cones, serially sectioned in their entirety, showed that growth cones were associated with the same radial fascicle as their axon. Growth cones also touched other cellular elements such as axons. However, the finding that callosal afferents, from the point at which they enter the cortex to their growth cones, were apposed to a continuous fascicle of radial fibers suggests that callosal axons are tracking along radial processes. We conclude that the majority of the radial processes within fascicles are likely to be glial, based on their relatively large diameters, electron-lucent cytoplasm with a regular array of microtubules, the presence of glycogen granules, occasional cytoplasmic protrusions lacking microtubules, and their consistent association with migrating neurons. We propose therefore that radial glia may serve a guidance function for growing callosal axons in their radial trajectory through the developing cerebral cortex. PMID- 1941094 TI - Antibody markers identify a common progenitor to sympathetic neurons and chromaffin cells in vivo and reveal the timing of commitment to neuronal differentiation in the sympathoadrenal lineage. AB - Using specific antibody markers and double-label immunofluorescence microscopy, we have followed the fate of progenitor cells in the sympathoadrenal (SA) sublineage of the neural crest in developing rat embryos. Such progenitors are first recognizable in the primordial sympathetic ganglia at embryonic day 11.5 (E11.5), when they express tyrosine hydroxylase. At this stage, the progenitors also coexpress neuronal markers such as SCG 10 and neurofilament, together with a series of chromaffin cell markers called SA 1-5 (Carnhan and Patterson, 1991 a). The observation of such doubly labeled cells is consistent with the hypothesis that these cells represent a common progenitor to sympathetic neurons and adrenal chromaffin cells. Subsequent to E 11.5, expression of the chromaffin markers is extinguished in the sympathetic ganglia but retained by cells within the adrenal gland. Concomitant with the loss of the SA 1-5 immunoreactivity in sympathetic ganglia, a later sympathetic neuron-specific marker, B2, appears. In dissociated cell suspensions, some B2+ cells that coexpress SA 1 are seen. This implies a switch in the antigenic phenotype of developing sympathetic neurons, rather than a replacement of one cell population by another. The SA 1----B2 transition does not occur for the majority of cells within the adrenal primordium. In vitro, most B2+ cells fail to differentiate into chromaffin cells in response to glucocorticoid. Instead, they continue to extend neurites and then die. Taken together, these data imply that the SA 1----B2 transition correlates with a loss of competence to respond to an inducer of chromaffin differentiation. Thus, the development of SA derivatives is controlled both by environmental signals and by changes in the ability of differentiating cells to respond to such signals. PMID- 1941095 TI - Spectrin isoforms in the mammalian retina. AB - Spectrin is a major component of the mammalian neuronal cytoskeleton. In the CNS, three isoforms of brain spectrin are known to exist: a cellular and dendritic isoform, (240/235E), related to neurons and glia; a cellular and axonal isoform, (240/235), related to neurons; and an isoform specific for astrocytes, (240/235A). In the present study, brain spectrins (240/235E) and (240/235) were localized within the mouse retina and optic nerve. Immunoblot analyses of proteins isolated from mouse retinas utilizing polyclonal antibodies to either brain spectrin (240/235) or brain spectrin (240/235E) revealed that these spectrins are present in the retina and that the two isoforms are the same molecular weights as those found in the brain. Immunocytochemical studies revealed that spectrin (240/235E) was localized in cell bodies of the inner nuclear, outer nuclear, and ganglion cell layers, and processes arborizing within the inner and outer plexiform layers. Spectrin (240/235) was distributed diffusely within the retina, lightly staining neurons in both the inner nuclear and outer nuclear layers, and the ganglion cell layer. In contrast to the situation found in the brain, spectrin (240/235) was but one of the axonal forms in the retina. We found that spectrin (240/235E) was also present in the axon rich fiber layer and in the optic nerve and was often associated with fibrous elements. Spectrin (240/235) was also detected in the nerve fiber layer and optic nerve, but this isoform was not localized to fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941096 TI - The monoclonal antibody E587 recognizes growing (new and regenerating) retinal axons in the goldfish retinotectal pathway. AB - E587 is a new monoclonal antibody against a 200 kDa cell-surface glycoprotein in the fish retinotectal pathway. The E587 antigen probably belongs to the class of cell adhesion molecules, and more specifically, to the family of L1-like molecules. The immunopurified protein is recognized by the antibody against the HNK1/L2 sugar epitope (associated with most cell adhesion molecules) and by a polyclonal antiserum against chick G4, which is related to the cell adhesion molecule L1 in mouse. Moreover the NH2-terminal sequence of E587 shows similarity with L1 and Ng-CAM. The E587 immunostaining pattern in the fish retinotectal pathway suggests that the E587 antigen is a growth-associated molecule on fish retinal axons. In fish embryos, all retinal axons are labeled. In adult fish, however, only the young axons from newly added ganglion cells carry E587 staining. After optic nerve transection (ONS) and retinal axonal regeneration, all axons reexpress the E587 antigen into their terminal processes in the tectal retinorecipient layers. The reexpression of the E587 antigen is temporally regulated, and E587 immunoreactivity declines by 7 months and disappears at 12 months after ONS. We hypothesize that the E587 antigen may mediate axon-axon associations. In its restricted appearance on young axons in normal adult fish, it may contribute to the selective fasciculation of the newest axons with young axons and thus participate in the creation of the age-related fiber organization in the fish optic nerve. PMID- 1941097 TI - A study of the mechanism of Ca2+ current inhibition produced by serotonin in rat dorsal raphe neurons. AB - Calcium currents and their modulation by 5-HT were studied using both whole-cell and single-channel patch-clamp techniques in acutely isolated adult rat dorsal raphe neurons. Evidence for three types of Ca channels (T, N, L) was obtained in both whole-cell and single-channel experiments. Approximately 4% of the total high-threshold Ca current (L-type) was sensitive to dihydropyridines (DHPs) while approximately 40% of the Ca current (N-type) was sensitive to omega-conotoxin (omega-CgTx). About 56% of the whole-cell current was insensitive to either DHPs or omega-CgTx and may thus represent a different kind of Ca current. 5-HT reduced raphe neuron Ca currents by approximately 50%, while slowing activation. 5-HT inhibited both omega-CgTx-sensitive and -insensitive Ca current. Inhibition by 5 HT was voltage dependent; prepulses to +80 mV lasting for 20 msec almost completely abolished the 5-HT-mediated inhibition. The voltage dependence of the response to 5-HT suggested that trains of action potentials might overcome the inhibition due to 5-HT. Trains of brief depolarizations were used to simulate action potentials; only about 5% of the 5-HT-induced inhibition was relieved by the trains. These results suggest that while large depolarizations could restore the Ca current inhibited by 5-HT, physiological stimuli, such as trains of action potentials, could not. The action of 5-HT was made irreversible by inclusion of GTP-gamma-S in the patch pipette, suggesting a G-protein mediation of the response to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941098 TI - Denervation does not alter the number of neuronal bungarotoxin binding sites on autonomic neurons in the frog cardiac ganglion. AB - The binding of neuronal bungarotoxin (n-BuTX; also known as bungarotoxin 3.1, kappa-bungarotoxin, and toxin F) was analyzed in normal and denervated parasympathetic cardiac ganglia of the frog Rana pipiens, n-BuTX blocks both EPSPs and ACh potentials at 5-20 nM, as determined by intracellular recording techniques. Scatchard analysis on homogenates indicates that cardiac ganglia have two classes of binding sites for 125I-n-BuTX: a high-affinity site with an apparent dissociation constant (Kd,app) of 1.7 nM and a Bmax (number of binding sites) of 3.8 fmol/ganglion and a low-affinity site with a Kd,app of 12 microM and a Bmax of 14 pmol/ganglion. alpha-Bungarotoxin does not appear to interfere with the binding of 125I-n-BuTX to either site. The high-affinity binding site is likely to be the functional nicotinic ACh receptor (AChR), given the similarity between its affinity for 125I-n-BuTX and the concentration of n-BuTX required to block AChR function. Light microscopic autoradiographic analysis of 125I-n-BuTX binding to the ganglion cell surface reveals that toxin binding is concentrated at synaptic sites, which were identified using a synaptic vesicle-specific antibody. Scatchard analysis of autoradiographic data reveals that 125I-n-BuTX binding to the neuronal surface is saturable and has a Kd,app similar to that of the high-affinity binding site characterized in homogenates. Surface binding of 125I-n-BuTX is blocked by nicotine, carbachol, and d-tubocurarine (IC50 less than 20 microM), but not by atropine (IC50 greater than 10 mM). Denervation of the heart increases the ACh sensitivity of cardiac ganglion cells but has no effect upon the number of high-affinity binding sites for 125I-n-BuTX in tissue homogenates. Moreover, autoradiographic analysis indicates that denervation does not alter the number of 125I-n-BuTX binding sites on the ganglion cell surface. n BuTX is as effective in reducing ganglion cell responses to ACh in denervated ganglia as it is in normally innervated ganglia. These results suggest that denervation alters neither the total number of nicotinic AChRs in the cardiac ganglion nor the number found on the surface of ganglion cells. These autonomic neurons thus respond differently to denervation than do skeletal myofibers. The increase in ACh sensitivity displayed by cardiac ganglion cells upon denervation cannot be explained by changes in AChR number. PMID- 1941099 TI - Calcium-activated chloride conductance in frog olfactory cilia. AB - We have measured the effects of cytoplasmic Ca2+ on the conductance of single cilia excised from frog olfactory receptor neurons. When free cytoplasmic Ca2+ is buffered at 0.1 microM, ciliary conductance is low. As Ca2+ is increased, ciliary conductance increases. Maximal conductance averages sevenfold higher than that measured in the absence of Ca2+. We estimate that the K1/2 for Ca2+ activation is 5 microM; the dose-response curve indicates some positive cooperativity of Ca2+ binding. Activation by Ca2+ is rapid and fully reversible. Most of the Ca(2+) activated current is carried by Cl- and persists in the absence of Na+ and K+. The Cl- channel inhibitor 3',5-dichlorodiphenylamine-2-carboxylate (300 microM) reduces the Ca(2+)-activated current by 90%. Odorants induce a Ca2+ influx in some olfactory receptor neurons, but the consequences of this influx for neuronal function are not well understood. Our findings allow us to predict that a Ca2+ influx would increase the permeability of the olfactory cilia to Cl-. How this would affect the neuronal potential is uncertain, since the equilibrium potential for Cl- in olfactory receptor neurons is unknown. PMID- 1941100 TI - Identification and characterization of cerebral-to-buccal interneurons implicated in the control of motor programs associated with feeding in Aplysia. AB - We identified candidate neurons in the cerebral ganglion that regulate feeding responses mediated by the buccal ganglion. Backfilling the cerebral-buccal connectives revealed that each cerebral hemi-ganglion contains approximately 20 neurons that project axons to the buccal ganglion. Three M-cluster neurons (CBI 1, CBI-2, CBI-3) and one E-cluster neuron (CBI-4) were identified as cerebral-to buccal interneurons (CBIs) based on position, morphology, synaptic connections, and ability to drive buccal motor programs (BMPs). CBI-1 responds to touch of the tentacles, lips, and buccal mass. It receives monosynaptic EPSPs from interganglionic, cerebral-to-buccal mechanoafferent (ICBM) neurons and monosynaptically excites buccal cells, some of which are also excited by the ICBMs. Tonic firing of CBI-1 usually evokes a single cycle of BMP activity. CBI-1 phase-shifts the rhythmic BMP driven by firing a dopaminergic neuron in the buccal ganglion. CBI-1 itself exhibits dopamine-like histofluorescence following formaldehyde-glutaraldehyde fixation. CBI-2 is excited by food stimuli applied to the lips. Constant-current intracellular stimulation of CBI-2 produces phasic firing of the cell that reliably evokes a rhythmic BMP that incorporates buccal and cerebral motor neurons, putative pattern-generating and pattern-initiating neurons, and neuromodulatory cells (metacerebral cells). CBI-4 also evokes a rhythmic BMP, but the details of its actions and synaptic effects differ from that of CBI-2. CBI-3 does not evoke a BMP, even though it is excited by food stimuli applied to the lips, and it makes monosynaptic connections (both excitatory and inhibitory) to many follower cells of the other CBIs. Firing of CBI-3 phase-delays the BMP driven by CBI-2. Since its activity is incorporated into BMPs and it provides direct inputs to elements of the feeding circuitry, it may play a role in pattern generation. The distinctive features of the CBIs suggest that the consummatory phase of feeding may be controlled by a population of interneurons that subserve different roles. PMID- 1941101 TI - Functional organization of human supplementary motor cortex studied by electrical stimulation. AB - The presence of somatotopic organization in the human supplementary motor area (SMA) remains a controversial issue. In this study, subdural electrode grids were placed on the medial surface of the cerebral hemispheres in 13 patients with intractable epilepsy undergoing evaluation for surgical treatment. Electrical stimulation mapping with currents below the threshold of afterdischarges showed somatotopic organization of supplementary motor cortex with the lower extremities represented posteriorly, head and face most anteriorly, and the upper extremities between these two regions. Electrical stimulation often elicited synergistic and complex movements involving more than one joint. In transitional areas between neighboring somatotopic representations, stimulation evoked combined movements involving the body parts represented in these adjacent regions. Anterior to the supplementary motor representation of the face, vocalization and speech arrest or slowing of speech were evoked. Various sensations were elicited by electrical stimulation of SMA. In some cases a preliminary sensation of "urge" to perform a movement or anticipation that a movement was about to occur were evoked. Most responses were contralateral to the stimulated hemisphere. Ipsilateral and bilateral responses were elicited almost exclusively from the right (nondominant) hemisphere. These data suggest the presence of combined somatotopic organization and left-right specialization in human supplementary motor cortex. PMID- 1941102 TI - Association of heparan sulfate proteoglycan with the neurofibrillary tangles of Alzheimer's disease. AB - The major intracytoplasmic lesion of Alzheimer's disease is the neurofibrillary tangle (NFT), which is primarily composed of paired helical filaments (PHFs). The mechanism responsible for the formation of PHFs, as well as their insolubility and apparent heterogeneity, is unknown. We found that basic fibroblast growth factor (bFGF) binds to heparinase-sensitive sites in NFTs. bFGF binding is due to a heparan sulfate proteoglycan (HSPG) immunocytochemically identified in NFTs. In the presence of polycations (e.g., Ca2+), HSPG will bind to free carboxyl groups in NFT proteins. HSPG binding may play a role in transforming normal soluble proteins into insoluble PHFs. PMID- 1941103 TI - Health promotion behaviors of private practice dental hygienists. AB - Today, there is increased emphasis in oral healthcare on health promotion and disease prevention. This is consistent with the focus of the dental hygiene profession. The purpose of this study was to investigate the health promotion behaviors of private practice dental hygienists within the ADHA District X region (Colorado, Montana, Utah, Wyoming). Statistical analysis procedures (frequencies, tests of statistical significance, and factor analysis) were performed on the questionnaire responses of 817 respondents who were employed in private practice settings. The results indicated that most respondents spent approximately five to 10 minutes on oral hygiene instruction (OHI) during a prophylaxis appointment, and focused on a variety of "traditional instructional" activities (e.g., discussing brushing and flossing, plaque control, caries, and periodontal disease). The majority of the respondents were satisfied with the amount of time they spent on OHI. When asked what factors limited the amount of time spent on OHI, the respondents most often cited "lack of interest on the part of the patient." Most respondents indicated there was no separate fee charged for OHI, even if separate OHI appointments were scheduled. The factor analysis indicated that some low-frequency behaviors (e.g., use of disclosants) were related more strongly to the concept of health promotion than were some high-frequency behaviors (e.g., use of a periodontal probe). The results of this study indicate that although health promotion services are provided frequently by dental hygienists, these services may not be provided consistently in the most effective way. Future research efforts could investigate the health promotion behaviors of private practice hygienists across the nation with a revised questionnaire to determine more adequately the status of these behaviors. PMID- 1941104 TI - Identification of nontraditional dental hygienists and their educational degrees. A strategy for baccalaureate program recruitment. AB - A pilot project was conducted to increase student applicant interest in a degree completion program. Since applicants reported a preference for employment in nontraditional settings, and questioned whether further education was needed, a strategy was developed to identify dental hygienists in Michigan who were so employed, and to establish their educational levels. Through telephone interviews, nontraditional dental hygienists were asked to identify additional professionals that were known within the nontraditional network. Nontraditional employment was defined as any setting other than a private dental office, with job responsibilities not confined to patient care; dental hygiene educators were excluded. The interviews were conducted by one graduate student, one day a week, for 15 weeks. The interviewer generated a list of 44 Michigan dental hygienists employed in nontraditional job settings as defined in this study. In terms of educational levels, 23% had certificate/associate degrees (n = 10) as their highest degrees, 41% had bachelor's degrees (n = 18), and 36% had master's degrees (n = 16). Non-patient care was the job description for 93% of the nontraditional settings (n = 41). The implied need for baccalaureate and/or graduate education for nontraditional employment has positively affected recruitment for the degree-completion program. The relationship that has been established with the network of nontraditional dental hygienists has also improved recruitment efforts and enhanced the curriculum. This project suggests that the definition of nontraditional dental hygiene employment should not be limited to settings which involve patient care. Similar projects should be initiated in other states to improve interest in baccalaureate education. PMID- 1941105 TI - A nonclinical model for predicting scaling and root planing case difficulty. AB - As students progress through their clinical education, the integration of patient types challenging the development of scaling and root planing skills is necessary. A clinical screening to determine case type is ideal; however, some programs do not have the time or resources for a clinical screening, and some patients do not want to take the time for the additional screening appointment. The intent of the screening process is to determine case type and/or treatment needs. In some cases, this information is used to match student educational requirements with patient needs. Even though an institution or program may have a clinical screening process, patient assignment can still be haphazard, resulting in an inequitable distribution of patient case types to students. It seems the problem is due, in part, to the absence of a mechanism for early identification and distribution of case types. The purpose of this study was to develop a model for initially predicting patient scaling and root planing case difficulty from nonclinical, patient variables obtained during a telephone interview. Dental hygiene student evaluation forms (n = 1,356) at the University of North Carolina at Chapel Hill School of Dentistry were gathered and categorized by patient case difficulty. A sample of charts was selected from each scaling classification. The scaling classifications were then subdivided into two samples for developing and testing the model. Variables selected from the patient charts as possible predictors were smoking status, race, age, gender, date of last prophylaxis, periodontal classification, and oral hygiene habits (brushing and flossing).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941107 TI - Basic studies on visible light-curing resin for denture base. Part 8. The hardening depth of denture relining material after penetration of light through the denture base resin. AB - A study was performed to examine how the duration of irradiation at the time of relining with visible light-curing material influences the depth of hardening of the relining material, in relation to the thickness of the denture base placed between the denture and the relining material. It was found that for a range of denture base thickness of 1-2.5 mm, a desirable degree of hardening could be obtained using an irradiation time of 20 s for relining material with a thickness of up to 4 mm used for the basal surface. PMID- 1941106 TI - Effect of systemic doxycycline administration on the subgingival microbial flora: a dark-field microscopy study. AB - The effect of systemically administered doxycycline hydrochloride on subgingival microbial plaque morphotypes was evaluated using dark-field microscopy. After 1 week of drug administration, while the percentage of coccoid bacteria showed a significant increase, the percentages of spirochetes, motile rods and non-motile rods tended to decrease. Since spirochetes and/or motile rods are considered to be associated with the pathogenesis of periodontal disease, the significant decrease in the proportions of these bacteria are considered to be important. Therefore, it is suggested that doxycycline may be beneficial for the treatment of periodontal disease as an adjunct to traditional therapeutic methods. PMID- 1941108 TI - Clinical course of multiple primary oral cancer: three of 13 cases with second primary tumor. AB - Of 124 patients with oral squamous cell carcinomas treated during the past 14 years, 13 developed second primary cancers with clinical symptoms in the same tissues or in organs different from those of the initial lesions during follow up. The second primary tumors also appeared in the oral cavity in 3 of the patients, the hypopharynx in 1, the esophagus in 2, the stomach in 2, the colon in 1, the thyroid gland in 2 and the lung in 2. Of the 3 patients with second tumors in the oral cavity, 1 underwent surgery after chemo- and radiotherapy and 2 underwent laser surgery or chemo- and radiotherapy only. The second primary cancers appeared on the contralateral or ipsilateral side, completely separate from the sites of the primary lesions during a period of 1 to 3 years. One patient with triple cancers involving the oral cavity, esophagus and hypopharynx is still alive after 15 years. The other two patients died of cervical or lung metastases after 3 years. PMID- 1941109 TI - Assessment of the nasopharyngeal area by cephalometry in cases of cleft lip and palate. AB - The nasopharyngeal area in 149 patients with cleft lip and palate and 157 normal individuals was evaluated by cephalometric radiography. The patients were male and female Caucasians, ranging in age from 12 to 16 years. Linear cephalometric parameters: (Ptm'-Sl; Ptm'-IPPF; IPPF-I, I-Ptm'), ANS angle and nasopharyngeal area were utilized. From comparative analysis of nasopharyngeal area in the cleft and the control groups, the following conclusions were made: 1) The nasopharyngeal area was smaller in the cleft group. 2) There was no correlation between ANS angle and nasopharyngeal area in either group. PMID- 1941110 TI - Suprascapular nerve entrapment. PMID- 1941111 TI - Technique of autoadrenal transplantation. PMID- 1941112 TI - Odontoid fractures. PMID- 1941113 TI - The role of neuroeffector mechanisms in cerebral hyperperfusion syndromes. AB - Cerebral hyperperfusion, a state in which blood flow exceeds the metabolic needs of brain, may complicate a number of neurological and neurosurgical conditions. It may account for the propensity with which hemorrhage, cerebral edema, or seizures follow embolic stroke, carotid endarterectomy, or the excision of large arteriovenous malformations, and for some of the morbidity that accompanies acute severe head injury, prolonged seizures, and acute severe hypertension. Hyperperfusion syndromes have in common acute increases in blood pressure, vasodilatation, breakdown of the blood-brain barrier, and the development of cerebral edema. These common features suggest the possibility that they share the same pathogenic mechanisms. It was believed until recently that reactive hyperemia was caused primarily by the generation of vasoactive metabolites, which induced vasodilatation through relaxation of vascular smooth muscle. However, the authors have recently established that the release of vasoactive neuropeptides from perivascular sensory nerves via axon reflex-like mechanisms has a significant bearing upon a number of hyperperfusion syndromes. In this article, the authors summarize their data and discuss possible therapeutic implications for blockade of these nerves or their constituent neuropeptides. PMID- 1941114 TI - Combined endovascular embolization and surgery in the management of cerebral arteriovenous malformations: experience with 101 cases. AB - The authors describe their experience with 101 cerebral arteriovenous malformations (AVM's) treated by endovascular embolization followed by surgical removal. Fifty-three patients presented with intracranial hemorrhage and 35 had seizures. Based on the classification of Spetzler and Martin, two AVM's were Grade I, 13 were Grade II, 26 were Grade III, 43 were Grade IV, and 17 were Grade V. Fifty-six AVM's were in the right hemisphere, 28 were in the left hemisphere, 12 were in the corpus callosum, and five involved the cerebellum. In 50 cases, presurgical obliteration of 50% to 75% of the AVM nidus was achieved by embolization, and in 31 cases this percentage increased to between 75% and 90%. In 97 (96%) patients, complete surgical removal of the AVM was obtained. Morbidity resulting from preoperative endovascular embolization was classified as mild in 3.9% of the cases, moderate in 6.9%, and severe in 1.98%. The death rate related to embolization was 0.9%. The immediate postsurgical morbidity was classified as mild in 5.9% of the cases, moderate in 10.8%, and severe in 5.9%. The overall long-term morbidity was mild in 5.9% of the cases, moderate in 6.9%, and severe in 1.98%. Two patients (1.98%) died due to intractable intraoperative hemorrhage and two (1.98%) as a result of postsurgical pulmonary complications. PMID- 1941115 TI - Stereotactic third ventriculostomy in patients with nontumoral adolescent/adult onset aqueductal stenosis and symptomatic hydrocephalus. AB - Sixteen consecutive patients with obstructive hydrocephalus due to nontumoral aqueductal stenosis of adolescent or adult onset underwent computerized tomography-guided stereotactic third ventriculostomy. Computer-assisted angiographic target-point cross-registration was used in surgical planning to reduce morbidity. The procedure was used as primary treatment in five previously unshunted patients and in 11 patients who had previously received shunts and who presented when their shunts became obstructed (five patients), became infected (five patients), or required multiple revisions (one patient). At the time of third ventriculostomy, shunt hardware was removed in patients with infected shunts and the distal element of the shunt was ligated in all patients with obstructed shunts except one, who later required repeat third ventriculostomy; the distal shunt was ligated at that time. Follow-up data (range 1 to 5 years, mean 3 1/2 years, after surgery) showed that only one of the 16 patients had undergone a shunting procedure after the third ventriculostomy. The other 15 patients are asymptomatic and shunt-independent. In previously shunt-dependent patients, the peripheral subarachnoid space and cerebrospinal fluid absorption mechanism remained patent in spite of shunts placed earlier. Therefore, in patients with obstructive hydrocephalus due to aqueductal stenosis of adolescent or adult onset, stereotactic third ventriculostomy should be seriously considered as primary surgical management in previously unshunted patients and in shunt dependent patients with obstructed or infected shunts. PMID- 1941116 TI - A clinicopathological study of dissecting aneurysms of the intracranial vertebral artery. AB - Five autopsied cases of dissecting aneurysms of the intracranial vertebral artery are reported and the literature is reviewed to clarify the clinicopathological correlations. In an autopsy series of 110 patients with subarachnoid hemorrhage (SAH), the incidence of this entity was 4.5%, with all five cases progressing rapidly to death from massive SAH. Cases of intracranial vertebral dissection can be divided clearly into two groups based on the clinical and pathological features. In the first group, the dissection is confined to the vertebral artery and a massive SAH develops caused by the rupture of the arterial wall. The plane of dissection is mainly subadventitial. In the second group, brain-stem infarction develops resulting from luminal occlusion by intramural hematoma. The plane of dissection is mainly subintimal, with the dissection extending to the basilar artery. The condition in the second group affects patients at a younger age. If the lesion is localized within the vertebral artery and does not extend to the basilar artery, the disease seems not to be fatal. The clinical features of the vertebral dissection are largely determined by the plane and extension of dissection. Vertebral artery dissection is due to many causative factors including hypertension, congenital or degenerative changes in the arterial wall, and anatomical and pathological characteristics of the vertebral artery. PMID- 1941117 TI - Operative management of bilateral facet dislocation. AB - Fifty-two patients with acute traumatic bilateral locked facets were treated at one trauma center during a 3 1/2-year period (July, 1987, to December, 1990). The patients presented with complete motor quadriplegia (34 cases), incomplete myelopathy (13 cases), or intact long-tract function (five cases). The injuries occurred at C2-3 (one patient, with intact function), C4-5 (12 patients), C5-6 (16 patients), C6-7 (19 patients), and C7-T1 (four patients). Immediate traction (with increasing weight and serial x-ray studies) and/or induction of general anesthesia and muscle relaxation reduced the dislocation in 40 patients, but 12 needed prompt operative reduction as their injuries failed to reduce within 4 hours. Stabilization was indicated for all patients, but three did not undergo surgery: two elderly patients with complete injuries (one refused surgery and one died), and one patient with multiple injuries (fusion was achieved by halo-vest immobilization for 3 months). Of the 49 patients treated operatively, 23 (44.2%) underwent surgery on the day of injury and 26 on a delayed basis (mean 8.7 days postinjury). Surgical treatment included fusion of the posterior facet to a spinous process (44 cases), an anterior Caspar plate technique (three cases), and both procedures (two cases). Of these 49 patients, three (6.1%) with complete injuries died due to an adult respiratory distress syndrome. Improvement of cord function, judged by functional grade change, was observed at discharge in 15 patients (31.9%) and in 15 (71.4%) of the 21 patients with a 1-year follow-up period. Of the 34 patients with complete myelopathy on admission, three are ambulatory after 1 year, and 13 others have gained function in at least one nerve root. It is concluded that prompt reduction (nonoperative or surgical) and internal stabilization facilitate recovery even in neurologically compromised patients, and that early operative intervention is a wiser option than conservative management. This report also documents a higher incidence of this injury without deficit (five of the 52 cases) than reported in other series. PMID- 1941118 TI - Morphological study of clinically nonsecreting pituitary adenomas in patients under 40 years of age. AB - Clinically nonsecreting pituitary adenomas removed at surgery from 69 patients under 40 years of age were studied by histological, immunocytochemical, and transmission electron microscopic examination. By morphological analysis, 19 tumors were found to be null-cell adenomas, 17 silent gonadotroph adenomas, 14 silent subtype 3 adenomas of unknown cellular origin, 13 silent subtype 1 or subtype 2 corticotroph adenomas, three oncocytomas, and three silent thyrotroph adenomas. These results indicate that the incidence of null-cell adenomas and oncocytomas, which are known to be the most common types of nonsecreting pituitary adenomas in patients over 40 years of age, is relatively low in younger patients. This trend is even more obvious in patients younger than 30 years of age. It can be concluded that clinically nonsecreting pituitary adenomas represent a heterogeneous group morphologically, and that the incidence of the different tumor types varies depending on the patient's age. These findings underline the importance of careful morphological studies. It is proposed that, in order for the correct morphological diagnosis to be made, tumors removed surgically from patients with clinically nonsecreting pituitary adenomas (especially younger patients) should be investigated not only by histological means but also by immunocytochemical and electron microscopic examination. The information obtained from such analysis may be useful in assessing prognosis and deciding on the appropriate treatment. PMID- 1941119 TI - Effect of chemical sympathectomy on cerebral blood flow in rats. AB - Thirty male Wistar rats, weighing 350 to 400 gm each, received stereotactic injections of 6-hydroxydopamine (300 micrograms/kg) into the left lateral ventricle. The same amount of saline was injected into a control group of 15 rats. Seven days after this procedure, cerebral blood flow (CBF) was measured by the hydrogen clearance method. A hypertensive condition at a mean arterial pressure of about 160 mm Hg was maintained for 1 hour by intravenous infusion of phenylephrine. In the 6-hydroxydopamine-treated group, CBF increased significantly after the elevation of systemic blood pressure compared with that in the control group, and cerebral autoregulation was impaired. After a 1-hour study, the specific gravity of the cerebral tissue in the treated group significantly decreased; electron microscopic studies at that time revealed brain edema. It is suggested that depletion of brain noradrenaline levels causes a disturbance in cerebral microvascular tone and renders the cerebral blood vessels more vulnerable to hypertension. PMID- 1941120 TI - Histopathology of experimental hematomyelia. AB - The pathology of hematomyelia was examined in 35 rats following the stereotactic injection of 2 microliters blood into the dorsal columns of the thoracic spinal cord. This experimental model produced a small ball-hemorrhage without associated neurological deficits or significant tissue injury. Histological sections of the whole spinal cord were studied at intervals ranging from 2 hours to 4 months after injection. In acute experiments (2 to 6 hours postinjection), blood was sometimes seen within the lumen of the central canal extending rostrally to the level of the fourth ventricle. Between 24 hours and 3 days, the parenchymal hematoma became consolidated and there was an intense proliferation of microglial cells at the perimeter of the lesion. The cells invaded the hematoma, infiltrated its core, and removed erythrocytes by phagocytosis. Rostral to the lesion, the lumen of the central canal was found to contain varying amounts of fibrin, proteinaceous material, and cellular debris for up to 15 days. These findings were much less prominent in the segments of the canal caudal to the lesion. Healing of the parenchymal hematoma was usually complete within 4 to 6 weeks except for residual hemosiderin-laden microglial cells and focal gliosis at the lesion site. It is concluded that the clearance of atraumatic hematomyelia probably involves two primary mechanisms: 1) phagocytosis of the focal hemorrhage by microglial cells; and 2) drainage of blood products in a rostral direction through the central canal of the spinal cord. PMID- 1941121 TI - The effect of age on outcome following traumatic brain injury in rats. AB - Age of the patient is one of the most important predictors of outcome following human traumatic brain injury. This study employs the fluid-percussion model to investigate the effects of aging on outcome following traumatic brain injury in rats. The results revealed that there was an age-associated increase in mortality rate following both low (1.7 to 1.8 atm) and moderate (2.00 to 2.25 atm) levels of traumatic brain injury. Age-related changes in systemic physiological, neurological, and histopathological indexes of brain injury were also examined following a low level of traumatic brain injury. Traumatic brain injury produced equivalent acute hypertension and increased plasma glucose levels in both young adult and aging rats. Injury produced an acute increase in heart rate in the young adult rat group, while the heart rate decreased in the aged rats. At low levels of brain injury, no significant gross histopathological alterations were produced in either age group. Neurological outcome was assessed by measuring the duration of suppression of a number of nonpostural and postural reflexes and more complex somatomotor functions (righting, escape, head support). Except for head support, there was a significant age-related increase in the duration of the suppression of these reflexes following brain injury. These data demonstrate that aging is associated with an increased mortality rate and greater acute neurological deficits following traumatic brain injury. These data also demonstrate the usefulness of the fluid-percussion model for studying the mechanisms responsible for the age-related increase in vulnerability to brain injury. PMID- 1941122 TI - Expression and modulation of major histocompatibility antigens on murine primary brain tumor in vitro. AB - Lysis of tumor cells by activated cytotoxic lymphocytes requires their recognition of antigens associated with major histocompatibility complex molecules. The authors studied the constitutive expression of Class I and Class II major histocompatibility complex antigens on mouse brain-tumor cells and the capacity of different cytokines and cytokine combinations to alter this expression in vitro. Cells from the murine glioma 26 (GL26), glioma 261 (GL261), and ependymoblastoma A (EpA) cell lines were established in monolayer culture and treated for 48 hours with either alpha interferon, gamma interferon, tumor necrosis factor alpha, tumor necrosis factor alpha plus gamma interferon, or interleukin-2. They were then analyzed by flow cytometry for baseline and cytokine-altered major histocompatibility complex expression. All cell lines had a similar constitutive major histocompatibility complex pattern with low Class I antigen expression and no detectable Class II antigen expression. Alpha interferon substantially induced and up-regulated Class I antigen expression, but had no effect on Class II antigen expression. Gamma interferon also stimulated up regulation of Class I antigen expression, generally doubling the anti-Class I antigen fluorescence of treated cells. Its effect on Class II antigen expression was more extensive. In the GL26 and GL261 cell lines the expression of Class II antigen determinants increased to 12 x and 14 x control values and as many as 75% of cells that had no detectable constitutive expression of Class II antigen expressed this antigen after priming with gamma interferon. The addition of tumor necrosis factor alpha to gamma interferon further increased Class II antigen expression on EpA tumor cells only. Interleukin-2 and tumor necrosis factor alpha alone had no effect on Class I or Class II antigen expression of any cell lines. It is concluded that Class I and Class II antigen expression in mouse glioma cell lines is induced and enhanced after treatment with certain cytokines in vitro. Use of these cell lines to create in situ primary brain tumors in C57BL/6 mice should provide an excellent animal system to study major histocompatibility complex modulation in brain tumor cells and to examine the potential impact of major histocompatibility complex up-regulation on the response of brain tumors to immunotherapy. PMID- 1941123 TI - A sacral dural arteriovenous fistula presenting with an intermittent myelopathy aggravated by menstruation. Case report. AB - The case is reported of a woman with a spinal dural arteriovenous fistula whose intermittent myelopathy became aggravated with menstruation. Her symptoms recurred in spite of successful acrylic embolization of the lateral sacral arteriovenous fistula. Repeat angiography showed venous drainage from the uterus toward the medullary vein. Total abdominal hysterectomy cured her symptoms. The pathophysiological basis for this peculiar clinical manifestation and its management are discussed. PMID- 1941124 TI - Cervical disc herniation presenting as a mass lesion posterior to the odontoid process. Report of two cases. AB - The authors report two cases of herniated intervertebral disc presenting as a mass posterior to the odontoid process and causing myelopathy in previously healthy elderly women. The differential diagnosis of a mass at the craniovertebral junction is reviewed, and the implications of these cases are discussed. PMID- 1941126 TI - Enlargement of basilar artery aneurysms following balloon occlusion--"water hammer effect". Report of two cases. AB - Two patients with distal basilar aneurysms were treated with intra-aneurysmal balloon occlusion. After apparently successful therapy, follow-up angiograms demonstrated aneurysm enlargement with balloon migration distally in the sac. Geometric mismatch between the base of the balloons and the aneurysm neck together with transmitted pulsation through the 2-hydroxyl-ethylmethacrylate (HEMA)-filled balloon directly contributed to aneurysm enlargement. In this report, the authors discuss the problems of progressive aneurysm enlargement due to a "water-hammer effect" and the possibility of hemorrhage following subtotal occlusion. PMID- 1941125 TI - Obstructive hydrocephalus caused by an abnormal vein in the aqueduct. Case report. AB - A case is reported of aqueductal stenosis caused by an abnormal draining vein and demonstrated by computerized tomography and magnetic resonance imaging. Placement of a ventriculoperitoneal shunt relieved the patient's progressive headaches. PMID- 1941127 TI - Hemorrhage into an intradiploic arachnoid cyst. Case report. AB - Intracranial arachnoid cysts are relatively rare; it is believed that they account for only 1% of all intracranial space-occupying lesions. When they occur in the intracranial cavity, they usually develop in relation to an arachnoid cistern as a pocket of cerebrospinal fluid within two layers of arachnoid membrane. Five cases of intradiploic arachnoid cysts have been reported, but an arachnoid cyst presenting as an extradural mass has not been described before. The authors present an unusual case of hemorrhage into a massive intracranial extradural arachnoid cyst with no intradural communication. PMID- 1941128 TI - Metastatic juvenile pilocytic astrocytoma. Case report. AB - The authors report the case of a metastatic juvenile pilocytic astrocytoma of the hypothalamic region in a 10-year-old boy. Eight years after craniotomy and radiation therapy, the tumor spread via cerebrospinal fluid pathways to the left cerebellar tonsil and the lumbosacral region. Histological evaluation of both the original hypothalamic and the new lumbosacral masses showed features of a slow growing juvenile pilocytic astrocytoma with no evidence of malignant transformation. The clinical implications and possible mechanisms of metastatic spread are discussed. PMID- 1941129 TI - Intradural extraosseous chordoma in the foramen magnum region. Case report. AB - Chordomas that are entirely extraosseous and intradural are extremely rare. The tumors described in the literature were observed mostly in the prepontine region. This is the first case reported of an intradural extraosseous chordoma occurring in the foramen magnum region. The tumor was totally excised. The distinction between an intradural extraosseous chordoma and a classic chordoma is important from a clinical viewpoint because of the potential for complete surgical excision and a more benign growth pattern. PMID- 1941130 TI - Extraosseous spinal chordoma. Case report. AB - An extraosseous extradural tumor of the lumbar region with the histological appearance of chordoma produced symptoms in a 58-year-old woman. The tumor occupied the epidural space and produced scalloping of the adjacent vertebral body and pedicle without associated bone destruction. The location of the tumor within Batson's plexus and lack of osseous connection facilitated complete removal. Although the lesion exhibited the classic histological features of a chordoma, it differed significantly in its extraosseous location. Like the rare intradural chordoma arising in the cranium, this tumor presumably represents neoplastic development in an extraosseous notochordal rest. PMID- 1941131 TI - Anomalous subarcuate loop. Technical note. AB - An anomalous subarcuate loop of the anterior inferior cerebellar artery is described in which the artery is adherent to or penetrates the posterior fossa dura in the subarcuate fossa. When encountered during acoustic neurilemoma surgery, the artery should be carefully mobilized along with a sleeve of dura to prevent its injury. PMID- 1941132 TI - Peter Bent Brigham Hospital. AB - The Peter Bent Brigham Hospital was established in Boston in 1913. The purchase of the site defined what would become one of the largest medical complexes in the world. This hospital was intended to be a university hospital based on the model created by Johns Hopkins University. The pioneering work of Harvey Cushing while at the Peter Bent Brigham Hospital is briefly touched on. PMID- 1941133 TI - Everyone is guilty in everything. The 1991 Harvey Cushing oration. AB - In the 1991 Cushing oration, Russian poet Yevgeny Yevtushenko examines the concept of guilt and responsibility for the condition of mankind. Literature and recent history offer examples of response to shame. He discusses the importance to the future of man of the acknowledgment of guilt and the concept of global patriotism. PMID- 1941134 TI - Fast diagnosis of abdominal infections and inflammations with technetium-99m HMPAO labeled leukocytes. AB - The diagnostic value of early 99mTc-HMPAO-leukocyte images (2 min, 0.5 hr, 2 hr and 4 hr) was studied in 87 prospectively performed investigations in 80 patients with a suspicion of abdominal inflammation or infection. Sensitivity, specificity and accuracy were 74%, 85% and 77% in the 2-min scans, 88%, 81% and 86% in the 0.5-hr scans, 95%, 85% and 92% in the 2-hr scans, and 96%, 92% and 95% in the 4 hr scans. Nonspecific bowel accumulation was seen in 7% of patients at 2 hr and in 28% at 4 hr but was easily distinguishable from pathologic activity. The uptake in early images represents an active accumulation of granulocytes at the site of inflammation rather than nonspecific blood-pool activity judged by results of 99mTc-HMPAO-RBC imaging. We found that imaging within 2 hr from injection has a high diagnostic value, and that the activity accumulates in areas of infection and inflammation faster than in the intestinal background. PMID- 1941135 TI - Imaging of inflammatory sites in the 1990s: new horizons. PMID- 1941136 TI - Noninvasive delineation of the effects of moderate aging on myocardial perfusion. AB - Aging is accompanied by a decline in many aspects of cardiovascular function but little is known regarding its influence on myocardial perfusion. Eleven young adults (mean age 25 +/- 4 (s.d.) yr) and 15 older adults (mean age 55 +/- 9 yr) without history or symptoms of cardiovascular disease were studied using H2 15O and positron emission tomography under resting conditions and following administration of intravenous dipyridamole. Myocardial perfusion at rest was similar in the older and younger subjects, averaging 1.17 +/- 0.35 and 1.16 +/- 0.32 ml/g/min, respectively (p = ns). Following dipyridamole, peak myocardial perfusion was blunted in the older subjects, averaging 3.12 +/- 1.09 ml/g/min compared with 4.25 +/- 1.54 ml/g/min in the young adults (p = 0.044). Accordingly, present standards for normal perfusion responses to intravenous dipyridamole may require adjustment for age. PMID- 1941137 TI - The transport of tyrosine into the human brain as determined with L-[1 11C]tyrosine and PET. AB - An alteration of dopaminergic transmission in the brain has been proposed for schizophrenia. To explore this, the rate constant for the intransport of L tyrosine across the blood-brain barrier in healthy controls and in patients with schizophrenia (DSM-III-R) was determined with PET and L-[1-11C] tyrosine as the tracer. Kinetics for tyrosine transport were determined according to a two compartment model using radioactivity data of arterial blood and brain tissue sampled between 1 and 3.5 min after a bolus injection of L-[1-11C] tyrosine. Radioactivity was measured every second in the blood and in 10-sec intervals in the brain tissue. In the normal controls the brain intransport rate constant for tyrosine was 0.052 ml/g/min with an influx rate of 2.97 nmol/g/min. The patients had a similar intransport rate constant (0.045 ml/g/min) but a lower influx rate of tyrosine 1.95 nmol/g/min (p less than 0.05). The patients' tyrosine concentrations in the blood were lower. For data sampled between 5 and 25 min, the net accumulation rate of tyrosine into the brain was 0.015 ml/g/min in the controls which did not differ to the patients' rate. However, the net utilization of tyrosine was lower in the patients (0.672 nmol/g/min) than in the controls (0.883 nmol/g/min) despite similar tissue concentrations of tyrosine. PMID- 1941138 TI - A decision analysis approach to the treatment of patients with suspected pulmonary emboli and an intermediate probability lung scan. AB - There remains no clear consensus as to the appropriate further investigation and management of the patient suspected of pulmonary embolism (PE) who has an intermediate lung scan. Clinical assessment is documented as unreliable, yet many of these patients are unlikely to be treated or to have further tests despite a 36% chance of having PE. Using Medical Decision Analysis, four management strategies for such patients have been examined in terms of mortality and morbidity up to 6 mo post-presentation. The strategies were: (1) treat all patients; (2) treat no patients; (3) perform pulmonary angiography; and (4) perform contrast venography. In the last two strategies, the patients with positive examinations are treated; those with negative examinations are not treated. An extensive literature review was performed to provide probability estimates of chance events and outcomes. If all patients are treated, there is 96.8% chance of survival, with an 85.8% chance of survival with no major complications. If no patients are treated, survival is 89.3% and complication free survival is 89.3%. Angiography and venography results were 96.7%, 93.1% and 94.6% and 89.6%, respectively. We conclude that in patients suspected of PE who have intermediate lung scan results, the optimal strategy is pulmonary angiography since this results in the highest survival with the lowest complications. PMID- 1941140 TI - Immunoscintigraphy for lung cancer detection: reality testing. PMID- 1941139 TI - Detection of suspected primary lung cancer by scintigraphy with indium-111-anti carcinoembryonic antigen monoclonal antibodies (type F023C5) AB - Immunoscintigraphy with 111In-labeled anti-CEA-Mab (F023C5i) was carried out in 66 patients strongly suspected for a primary lung cancer and in 8 control patients suffering from different chest diseases. A sensitivity of 0.90, a specificity of 0.45 and an accuracy of 0.85 were calculated. False-negative results were mainly obtained in patients in whom the size of the lesion was below 2 cm and the tumor was centrally located. All patients affected by small-cell carcinoma were correctly identified. In 89% of the patients, a positive immunoscintiscan was associated with the presence of the antigen in the tumor. False-positive results were observed in control patients suffering from different chest diseases due to the nonspecific uptake of the tracer. The tumor definition was generally better after 120 hr than at an earlier time after injection due to the reduction of background activity. SPECT imaging defined the tumor better in each patient but did not reveal any tumor not seen on planar studies. PMID- 1941141 TI - Inadequate exercise leads to suboptimal imaging. Thallium-201 myocardial perfusion imaging after dipyridamole combined with low-level exercise unmasks ischemia in symptomatic patients with non-diagnostic thallium-201 scans who exercise submaximally. AB - This study was undertaken to establish the additional value of 201TI imaging after dipyridamole in combination with low-level exercise in 15 symptomatic patients with non-diagnostic 201TI scans, who exercised submaximally. Most patients had angina, ST-segment depression and even exertional hypotension and were referred for stress 201TI testing for determining the functional significance of known coronary artery disease. Six patients with a normal exercise 201TI test and one patient with an apical defect only were found to have 37 segments (of 105 segments) with reversible perfusion defects after dipyridamole infusion. One patient showing two reversible defects after exercise had five reversible segments after dipyridamole. Seven patients with fixed defects in 28 segments after exercise and two with small areas of border zone ischemia in seven additional (sub)segments, demonstrated fixed in defects in only nine segments but reversible defects in 40 segments after dipyridamole. Quantitative analysis resulted in 24.8 +/- 28.5 (mean value) sample points below 2 s.d. of the mean normal uptake after exercise, which increased to 72 +/- 26.5 after dipyridamole infusion (p less than 0.005). The washout analysis resulted in a mean value of 5.5 +/- 8.1 sample points below -2 s.d. after exercise, increasing to 33.3 +/- 22.1 after dipyridamole (p less than 0.005). Thallium-201 myocardial perfusion imaging after dipyridamole combined with low-level upright bicycle exercise may unmask scintigraphic evidence for ischemia in symptomatic patients who would otherwise have non-diagnostic imaging studies during submaximal exercise. PMID- 1941142 TI - Infectious imaging with indium-111-labeled nonspecific polyclonal human immunoglobulin. AB - Nonspecific polyclonal immunoglobulin (IgG), prepared from pooled human serum gamma globulin and labeled with 111In has been reported to be equivalent to antigen-specific antibody in the detection of focal infection or inflammation during the first 24 hr after injection. We describe our experience in a Phase II clinical study using 111In-IgG in 15 patients (8 males, 7 females) ranging from 26 to 80 (mean = 50) yr of age with suspected focal infection/inflammation. Pathologic confirmation was obtained in 5/15 cases. A combination of clinical course, laboratory results, and other imaging procedures were used to categorize the other 10 patients. One possible false-negative involved a presumed aspiration pneumonia in a patient with a history of aspiration, bibasilar infiltrates on chest film, and no other identified source of infection. Otherwise, there were 10 confirmed positives, 4 confirmed negatives, and no false-positives. Our findings confirm earlier reports that 111In-IgG may be a superior imaging agent for infection/inflammation with practical advantages over 67Ga-citrate and 111In labeled leukocytes. PMID- 1941143 TI - A comparison of scintigraphy, thermography, ultrasound and phlebography in grading of clinical varicocele. AB - Varicocele, a varicosity of the pampiniform plexus, usually on the left side, is a common urologic problem. It may be associated with symptoms of local discomfort or abnormal spermatogenesis. Internal spermatic vein phlebography is the "gold standard" investigative technique, but it is invasive. Noninvasive studies include: labeled blood-pool scintigraphy, thermography and ultrasound. Two hundred sixty-three patients were investigated with various combinations of these modalities. The degree of abnormality for each modality was graded semiquantitatively and the results compared. In addition, the results of semen analysis were correlated to imaging results. Ninety-six patients were investigated with all four tests (scintigraphy, thermography, ultrasound and phlebography). The correlation of positive phlebography to positive scintigraphy was 98%, to thermography 100% and to ultrasound 98%. The concordance (grade for grade) was 71% for scintigraphy, 68% for thermography and 62% for ultrasound. There was no obvious correlation between abnormalities of semen analysis and grading of varicocele. We conclude that the diagnostic accuracy and grading of severity by noninvasive techniques (including scintigraphy) compare very favorably with that of phlebography. Moreover, scintigraphy allows the noninvasive evaluation of reflux through the internal spermatic vein, which may be useful in planning therapy. PMID- 1941144 TI - Follow-up study of postoperative patients with thyroid cancer by thallium-201 scintigraphy and serum thyroglobulin measurement. AB - The utility of 201TI scintigraphy and thyroglobulin measurement in the follow-up observation of postoperative patients with thyroid cancer was evaluated. Thallium 201 scintigraphy was performed in 149 postoperative patients with thyroid cancer. Serum thyroglobulin concentration was concomitantly evaluated in 86 patients. Among 55 patients with positive 201TI scans, 51 patients (92.7%) had recurrent diseases, while 80 of 94 patients (85.1%) with negative scans were free of disease. Twenty-five of 28 patients (89.3%) with elevated thyroglobulin levels were recurrent and 43 of 58 patients (74.1%) with normal thyroglobulin level had no recurrence nor metastasis. All 19 patients with positive 201TI scans and elevated thyroglobulin level had recurrent lesions. Seven of 10 patients with negative 201TI scans and elevated thyroglobulin level showed the presence of metastasis. By concomitant measurement of serum thyroglobulin, more than half of the recurrent patients with negative 201TI scintigraphy were detected. Both 201TI scintigraphy and serum thyroglobulin measurement should be undertaken in the follow-up evaluation of postoperative patients with thyroid cancer. PMID- 1941145 TI - An evaluation of forearm bone mineral measurement with dual-energy X-ray absorptiometry. AB - Dual-energy x-ray absorptiometry (DEXA) has been reported to be a valuable means of bone mineral measurement of the lumbar spine and hip. In order to determine whether DEXA could be as useful for bone mineral analysis of the forearm, we compared its accuracy, precision and measurement performance to single-photon absorptiometry (SPA). There was high correlation between these techniques for integral bone mineral density in standard aluminum tubes (r = 0.99) and 30 adult volunteers or patients with osteoporosis (r = 0.95). The mean short-term precision of DEXA was 0.9% in vitro and about 1.5% in vivo. DEXA produced excellent bone images which enhance long-term in vivo precision. The measurement performance of both instruments was largely unaffected by localized fat deposits or increases in forearm thickness or proportion of fat subcutaneously. We conclude that DEXA is a clinically useful alternative to SPA for forearm bone mineral assessment. PMID- 1941146 TI - Safety of dipyridamole-thallium imaging in high risk patients with known or suspected coronary artery disease. AB - The effects of an oral dipyridamole suspension were studied in 400 consecutive patients to determine if certain subsets of patients were at greater risk of suffering major complications. Most patients (69%) experienced at least one side effect. Severe chest pain, severe hypotension, and severe dyspnea occurred in 9%, 2.5%, and 0.3% of patients respectively. Two patients were hospitalized for persistent chest pain but none suffered a myocardial infarction, malignant ventricular arrhythmia, or death. The test was found to be safe for patients over 70 yr old. Severe dyspnea was rare even among patients with lung disease who were withdrawn from theophylline prior to testing. Patients with three-vessel coronary artery disease were more likely to experience severe chest pain and those with significant left ventricular dysfunction were more likely to develop severe hypotension. In 99.5% of patients, side effects were promptly reversed by aminophylline. Dipyridamole-thallium imaging has an acceptable safety profile for a wide variety of patients, including those with severe coronary disease and/or left ventricular dysfunction. PMID- 1941147 TI - Dipyridamole/thallium-201 imaging: how safe is it? When should it be used? PMID- 1941148 TI - Monitoring tumor radiotherapy. PMID- 1941149 TI - The localization of indium-111-leukocytes, gallium-67-polyclonal IgG and other radioactive agents in acute focal inflammatory lesions. AB - A variety of radioactive agents, injected directly intravenously have demonstrated foci of inflammation by gamma camera imaging, avoiding the in vitro preparation of labeled leukocytes. This study sought to find out if any of these agents mimicked the biodistribution in abscesses and non-target organs of labeled mixed leukocyte suspensions. Eight different agents were compared with 111In oxine labeled leukocytes in an acute soft tissue E. coli abscess and an acute arthritic lesion in 24 dogs one day after intravenous administration. These included 67Ga-citrate, human and canine polyclonal immunoglobulin (IgG), rabbit anti-dog polyclonal IgG, serum albumin, monoclonal antibody TNT-1 F(ab')2 against nuclear antigens, 57Co-porphyrin and serum albumin nanocolloid. None of these agents achieved abscess concentrations approaching those obtained with labeled leukocytes, and their abscess/blood and abscess/muscle concentration ratios were considerably lower. No statistically significant differences were found between the different radiolabeled proteins evaluated. The abscess concentration of 99mTc nanocolloid was much lower than that of other agents, and the results with the oldest agent, 67Ga-citrate, were disappointing in these acute experiments. PMID- 1941150 TI - Indium-111-labeled low-density lipoprotein binds with higher affinity to the human liver as compared to iodine-123-low-density-labeled lipoprotein. AB - The interaction of 111In-low-density lipoprotein (LDL) and 123I-LDL with human liver-plasma membranes was investigated and compared. LDLs were isolated by sequential ultracentrifugation and radiolabeled either with 123I (using lodogen or iodine-monochloride) each followed by purification with gel-chromatography or dialysis) or 111In (using cyclic DTPA-anhydride). LDL concentrations of 0.1 to 32 micrograms protein/ml were used for direct binding assays investigating the specific binding of labeled LDL (in the presence of a 50-fold excess of unlabeled LDL) to human liver apoB-receptors. In separate experiments, displacement of bound 111In-(123I)-LDL by unlabeled LDL was studied. Human liver plasma membranes bound 239 +/- 26 ng protein of 111In-LDL/mg protein and 148 +/- 18 ng protein of 123I-LDL/mg protein specifically (p less than 0.001). The corresponding dissociation constants were 0.6 +/- 0.2 and 1.2 +/- 0.7 micrograms protein/ml, respectively (p less than 0.001). The capacity of unlabeled LDL to displace bound 111In-LDL was four times higher than that for 123I-LDL (IC50: 1.7 +/- 0.7 versus 7.7 +/- 1.0 micrograms protein/ml). No significant differences among the different methods of iodination of LDL were found. The findings show that 111In labeled lipoproteins might be a better ligand for lipoprotein-receptor binding studies as compared to radioiodinated lipoprotein products. PMID- 1941151 TI - Neutron-activated holmium-166-poly (L-lactic acid) microspheres: a potential agent for the internal radiation therapy of hepatic tumors. AB - Biodegradable Poly(L-lactic acid) microspheres containing neutron-activable 165Ho were designed for internal radiation therapy of hepatic tumors. Spheres composed of Poly(L-lactic acid) (PLA) were prepared with excellent reproducibility containing up to 36% of a holmium complex. The prepared spheres were irradiated in a high neutron flux converting 165Ho to 166Ho (Emax = 1.84 MeV, half-life = 26.9 hr). Thus, these microspheres can be prepared under conditions that do not require the handling of a hazardous radionuclide, and then irradiated just prior to administration. In vitro studies in plasma (n = 6) revealed 97.3% (+/- 1.9) retention of 166Ho in the microspheres after 240 hr. PLA spheres administered via the portal vein in rabbits (n = 6) show 94.5% (+/- 3.4) retention of the original 166Ho activity in the liver after 6 days. PMID- 1941152 TI - Lymphoscintigraphic abnormalities in venous thrombosis. PMID- 1941153 TI - Benefit of tomography in the scintigraphic localization of cerebrospinal fluid leak. AB - A CSF leak was demonstrated by tomography after planar acquisition failed to localize it. The rotatogram was more definitive than the reconstructed images in showing the leak. Tomography should be considered when the leak may be in an unusual location and the patient does not have rhinorrhea or otorrhea. Tomography allows a complete 360 degrees survey to examine for the best angle for inspection of the leak, whereas the empirically oriented planar study can sample only limited projections, particularly if given time limitations for acquisition. PMID- 1941154 TI - Simple quantification of regional myocardial uptake of fluorine-18-deoxyglucose in the fasting condition. AB - Quantitative measurement of myocardial uptake of fluorine-18-deoxyglucose (FDG) is required for assessing tissue viability in the fasting state due to suppressed FDG uptake in the normal myocardium. A simple FDG uptake index (% dose per 100 ml tissue) has been introduced to compare with the fractional FDG uptake in 21 patients who underwent serial arterial blood sampling (14 under fasting and 7 under post-prandial conditions) and to measure the normal range in each myocardial segment in the study of 10 normal subjects (all in the fasting condition). Since the integral of plasma FDG values correlated with the body weight corrected injected FDG dose (r = 0.82), an excellent correlation was observed between the FDG uptake index and the fractional FDG uptake (r = 0.98) in the fasting condition. In addition, the FDG uptake index correlated well with the regional metabolic rate of glucose calculated with the Patlak graphic analysis (r = 0.99). But this correlation was different in the postprandial condition and in the fasting condition in diabetic patients. In the study of normal subjects, the FDG uptake index was slightly higher in the lateral and inferior segments, as compared to the septal and anterior segments (p less than 0.05, each). We conclude that the FDG uptake index is considered as a simple and reliable parameter for quantitative assessment of myocardial FDG uptake in the nondiabetic patients in the fasting condition. Since its uptake was heterogeneous, FDG uptake should be carefully evaluated for assessing myocardial viability by comparing normal values in each segment. PMID- 1941155 TI - Development and clinical performance of an automated, portable tungsten 178/tantalum-178 generator. AB - An automated, portable 178W/178Ta generator system has been developed for use in first-pass radionuclide angiography studies with the multiwire gamma camera. Eluant (0.03N HCI, 0.1% H2O2) and buffer (0.13 N Na2HPO4) are delivered with a dual channel peristaltic pump. The generator column is a borosilicate glass tube with 30 microns fused glass frit containing 0.75 ml AG1X8 anion exchange resin. This column and associated plumbing are assembled, integrally autoclaved, and then connected to sterile eluant and buffer containers. Automatic push-button elution directly into an injection syringe is provided. Three such generators have been employed in the study of 78 patients in the catheterization laboratory utilizing a mobile, multiwire gamma camera. Over a 3-mo period, 301 sterile pyrogen-free doses ranging from 15 to 99.5 mCi were supplied with a mean breakthrough level of 2.1 +/- 3.6 microCi. This automated, portable, high-yield 178W/178Ta generator represents a major advancement that will significantly facilitate first-pass radionuclide angiography with 178Ta and the multiwire gamma camera. PMID- 1941157 TI - Comparison of left anterior oblique and geometric mean gastric emptying. AB - A left anterior oblique image (LAO) and the geometric mean of anterior and posterior counts have both been proposed as methods for acquiring gastric emptying data. Both approaches are used to correct for the changes in attenuation that occur as the depth of radiolabeled solids changes during gastric emptying. These two methods were compared by using a power exponential curve fit to calculate a lag phase, an equilibrium emptying rate, and a half-time for gastric emptying in 20 patients. There were no significant differences (mean +/- 1 s.e.m.) in the measured half-emptying time (115 +/- 10 versus 104 +/- 7 min) (p = 0.08) or rate of gastric emptying (0.015 +/- 0.002 versus 0.015 +/- 0.002 min-1) (p = 0.56) for LAO imaging versus the geometric mean. However, the LAO measurements of the lag phase were significantly higher (69 +/- 7 min) than the geometric mean (53 +/- 6 min) measurements (p = 0.004). This resulted in 4/20 (20%) of patients with normal geometric mean lag phase measurements who would have been reclassified as abnormal using the LAO method. PMID- 1941156 TI - Myocardial tissue fraction--correction for partial volume effects and measure of tissue viability. AB - We have compared two independent methods of correcting the systematic underestimation in measurements of myocardial radiotracer concentration due to wall motion and small transmural wall thickness in cardiac PET studies. The first technique was based on measurement of the tissue fraction by fitting 15O-labeled water dynamic PET data. The other technique involved the subtraction of the C15O blood volume scan from the transmission data, producing an image of extravascular density. In normal myocardial regions, both values were observed to be about 60% of myocardial tissue density. The tissue fraction was approximately 10% larger than the extravascular density in normal tissue regions. The ratio of alpha/Dev indicates the proportion of the total extravascular tissue for a given ROI that is perfusable by water--independent of the partial volume effect. This ratio was confirmed to be the expected value in normal tissue regions but was reduced in regions of infarction. The use of 15O-water, C15O and transmission data may aid in the differentiation between perfusable and nonperfusable tissue in the infarcted myocardium. PMID- 1941158 TI - Brain tumor uptake of iodo-alpha-methyl-tyrosine. PMID- 1941159 TI - False-positives in immunoscintigraphy. PMID- 1941160 TI - Diagnosing prosthetic joint infection. PMID- 1941161 TI - Finance for nurse managers: a software package. PMID- 1941162 TI - HIV report. PMID- 1941163 TI - Administrative prosperity: principle III, nurturing a creative spirit. PMID- 1941164 TI - Graduate nursing education. PMID- 1941165 TI - Advanced directives. In search of self-determination. AB - Patients are seeking self-determination in health-care through the use of advanced directives. The author discusses advanced directives focusing on patient rights in decision making, autonomy, and the right to refuse life-sustaining treatment. Highlighted is the Patient Self-Determination Act of 1990, including strategies for its implementation in healthcare agencies. PMID- 1941166 TI - Compensation of home health, public health, and hospital nurses. Extrinsic and intrinsic rewards. AB - Despite the proliferation of home health agencies and increased numbers of nurses working in these settings, little is known about home health nurses or how they might differ from their public health and hospital counterparts. The authors discuss differences in monetary compensation and skill usage, as well as the relationship between compensation and retention, among hospital, home health, and public health staff nurses. The results show that these nurses receive different intrinsic and extrinsic rewards and that their reasons for remaining with their employers are similar, yet unique. Implications for nurse administrators and educators are discussed, along with recommendations for further research. PMID- 1941167 TI - Recruiting and retaining registered nurses in rural community hospitals. Some administrative assessments. AB - The costs and impacts associated with the recruitment and retention of nurses are substantial. In rural areas, these efforts are hampered by the recurring maldistribution of available nurses away from such environments. Based on a survey of 195 directors of nursing (DONs) practicing in rural community hospitals, the authors compare administrative assessments of recruitment and retention efforts of DONs practicing in various-sized rural facilities. Current full-time equivalent registered nurse staff vacancy rates are also reported in relation to these differing assessments. PMID- 1941168 TI - Nurse satisfaction with work in rural hospitals. AB - Little is written about retention and recruitment of nurses in small rural hospitals. The authors present findings of a nursing study that identified factors that encouraged and deterred nurses to practice in the rural environment. PMID- 1941169 TI - Empowering nurses. Patient satisfaction with primary nursing in home health. AB - Responsibility, accountability, and authority are the tools of primary nursing that enable nurses to impact patient care. It is important to determine if nurses empowered by a primary nursing care delivery system can positively influence patient outcomes. The authors describe an outcome audit conducted to study patient satisfaction with nursing care, one indicator of quality patient care. PMID- 1941170 TI - There is a better way ... an admission assessment coordinator. PMID- 1941171 TI - Automated nursing documentation system provides a favorable return on investment. AB - Severe competition for the limited investment capital available and the high acquisition cost of bedside terminal systems require that the full benefit potential they offer be identified and realized. The authors discuss a multiple phase study process used to: 1) identify the savings potential offered (to cost justify its acquisition); and 2) assure the savings potential offered was realized. PMID- 1941173 TI - Marketing home health care. AB - This case study focuses on the physician as an important customer for home care services. The author describes how Visiting Nurse Service of New York developed and implemented a direct sales strategy to increase the number of referrals from physicians. Five of the direct sales consultants were registered nurses. The tactics used to increase the percentage of cases referred directly by physicians are discussed. PMID- 1941172 TI - HIV test cost debated. PMID- 1941174 TI - Common-sense ethics in administrative decision making. Part II, Proactive steps. AB - This article is the second in a two-part study on common-sense ethics. In Part 1 (October 1991 JONA), the authors presented preparatory steps for the nurse administrator to consider in the management of diverse ethical issues. In Part 2, the authors delineate proactive steps to facilitate the resolution of administrative problems with economic, social, and ethical dimensions. They apply the model to the problem of the nursing shortage. Although no guarantees are assured in following the steps, decision making may be facilitated during the ethical conflict. PMID- 1941175 TI - The possible, the probable, and the unlikely: forecasting the future. AB - Nurse executives, administrators, and managers are constantly being challenged by the changes in healthcare. Although it sometimes seems there is really nothing new, proactive visionary nurse administrators can rediscover, redesign, and redirect their own and others' activities to achieve organizational effectiveness. Such approaches require periodic examination of all strategies and practices--past, present, and future--for their relevance, practicality, and success. The editors of "Executive Development" reflect on topics important to organizational life. PMID- 1941176 TI - Rudolf Schoenheimer and the concept of the dynamic state of body constituents. AB - In 1935 Rudolf Schoenheimer (1898-1941) introduced the isotopic tracer technique in metabolic research. The results of his experiments led to a new view of metabolism and nutrition and the evolution of a concept of "continual regeneration," i.e., of continual release and uptake of substances by the cell and, thus, of a "dynamic state of body constituents." This dynamic view of metabolism can be traced back to the thinking of some investigators of the 19th and early 20th century, notably C. Bernard and F. G. Hopkins. It was Schoenheimer, however, who provided clear experimental evidence of the dynamic concept of metabolism. PMID- 1941177 TI - Plasma very low density lipoproteins from male rats fed casein or soybean protein diets: a comparison of fatty acid composition and influence on prostanoid production. AB - In studies with male rats fed for 4 wk semipurified diets containing olive oil and casein or soybean protein, protein-dependent effects were observed in the fatty acid composition of the VLDL lipids, especially with regard to the pattern of polyunsaturated fatty acids. Compared with VLDL from rats fed soybean protein diet (S-VLDL), VLDL from casein-fed rats (C-VLDL) contained a greater level of oleic acid, and a reduced level of linoleic acid and arachidonic acid, in the phosphatidylcholine fraction. The proportion of 5,8,11-eicosatrienoic acid, 20:3 (n-9), varied among the different lipid classes. The highest concentration of this fatty acid (13% by weight of total fatty acids) was observed in the phosphatidylinositol fraction of C-VLDL. The level of linoleic acid was approximately halved in the triacylglycerol and cholesteryl ester fractions of C VLDL compared with S-VLDL. When mouse peritoneal macrophages were incubated with different concentrations of S-VLDL, a saturable accumulation of 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) was observed in the cell medium. In contrast, very low levels of 6-keto-PGF1 alpha and TXB2 were observed in the cell medium of macrophages incubated with C-VLDL at different lipoprotein concentrations, suggesting that the composition of VLDL may play an important role in relation to cellular prostanoid metabolism. PMID- 1941178 TI - 13-cis-retinoic acid alters methionine metabolism in rats. AB - The effect of dietary 13-cis-retinoic acid (CRA) on hepatic methionine metabolism was examined in young male rats. Rats were fed a 10% casein diet (controls) or this diet supplemented with L-methionine (10 g/kg diet), with or without the addition of CRA (100 mg/kg diet), for 10 d. Methionine-supplemented rats exhibited 7.3- and 1.7-fold greater concentrations of hepatic S adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), respectively, relative to controls, which resulted in a 4.9-fold greater SAM:SAH ratio. Likewise, hepatic methionine and taurine concentrations were 6.9- and 4.3-fold greater, respectively, in methionine-supplemented rats than in controls. The addition of CRA to the methionine-supplemented diet prevented the elevations in the hepatic methionine concentration and the SAM:SAH ratio, whereas taurine levels were greater than in methionine-supplemented rats. In rats pretreated with the methionine-supplemented diet, a reduction in the SAM:SAH ratio occurred within 2 d following the addition of CRA to the methionine-supplemented diet. Rats receiving the methionine-supplemented diet exhibited 9.2- and 3.7-fold greater urinary taurine and inorganic sulfate excretions, respectively, relative to controls. Addition of CRA to the methionine-supplemented diet significantly reduced sulfate excretion by 21%. These findings indicate that dietary CRA has the ability to alter the catabolism of methionine and subsequently influence hepatic transmethylation as reflected by the SAM:SAH ratio. PMID- 1941179 TI - Use of a four-parameter logistic equation to evaluate the response of growing rats to ten levels of each indispensable amino acid. AB - Over a 21-d period, 400 [four rats/level, 10 levels/amino acid, 10 indispensable amino acids (IAA)] male weanling rats (65.9 +/- 0.3 g; mean +/- SEM) were fed diets with one of 10 levels of each of the 10 IAA. In addition, four rats were fed an amino acid-free diet and 16 rats were killed on d 0 for individual body composition. With the exception of the limiting amino acid (LAA), an increment (35% of the requirement) of each IAA was added to the mixture to insure that the LAA remained first limiting. A four-parameter logistic equation was used to describe the nitrogen and weight gain responses of rats to each IAA. Conservation of nitrogen, defined as a predicted y-intercept value greater than the value observed for rats fed an amino acid-free diet (-0.304 +/- 0.023 g N/21 d), was seen when diets devoid of total aromatic amino acids or lysine (-0.062 +/- 0.013 g N/21 d) or histidine, leucine, tryptophan or valine (-0.115 +/- 0.011 g N/21 d) were fed. When total sulfur amino acids were first limiting, diminishing returns (a decrease in the first derivative) was evident from zero intake to Rmax (estimated asymptotic response maximum). In contrast, when other IAA were limiting, diminishing returns were apparent after approximately the first third of the full response. Based on the first derivative of the response curves, the efficiency of nitrogen gain depends on the LAA. The dietary LAA would be expected to influence the shape of the response curve and therefore influence the quantitative aspects of diminishing returns. PMID- 1941180 TI - High propionic acid fermentations and mineral accumulation in the cecum of rats adapted to different levels of inulin. AB - The digestive and metabolic effects of inulin (from chicory) were studied in rats adapted to semipurified diets containing 0, 5, 10 or 20% inulin (wt/wt). Moderate levels of inulin (5-10%) did not significantly affect food intake or body weight gain. Dietary inulin resulted in considerably greater cecal fermentation and a significantly greater intraluminal concentration of propionate (peaking at 58.4 mmol/L). A lower concentration of acetate (42.6 mmol/L) was observed in rats fed 20% inulin. Lactic fermentations were observed in rats fed the 10 or 20% inulin diets. The cecal pool of volatile fatty acids tended to reach a plateau in rats fed diets containing more than 10% inulin (up to 600-700 mumol), but volatile fatty acid absorption was a slightly hyperbolic function of the dietary inulin level. Butyrate absorption was proportionally lower than that of propionate. Inulin-containing diets induced an enlargement of the cecal pool of calcium, phosphate and (to a lesser extent) magnesium. There was also an enhanced absorption of these divalent cations. The cecal pool of bile acids was greater in rats fed inulin, and this oligosaccharide displayed a slight hypocholesterolemic effect, even in rats fed the 5% inulin diet. However, plasma triglycerides were depressed only in rats fed the 20% inulin diet. In conclusion, inulin seems very effective in promoting propionic fermentation and in enhancing the calcium content of the large intestine. However, high levels of inulin (greater than 10%) may affect growth in rats and lead to acidic (pH 5.65) cecal fermentation. PMID- 1941181 TI - Pyridoxal-5'-phosphate and pyridoxal biokinetics in male Wistar rats fed graded levels of vitamin B-6. AB - Biokinetic parameters of plasma pyridoxal-5'-phosphate (PLP) and pyridoxal (PL) disposition were studied in male Wistar rats (age 8 mo) fed a purified diet containing less than 0.5, approximately 3 or approximately 6 mg pyridoxine.HCl/kg diet from weaning, with animals fed the 6 mg/kg diet serving as the control group. Basal plasma PLP concentration was lower in both the less than 0.5 and 3 mg/kg diet groups than in control animals (98 +/- 12, 314 +/- 40 and 514 +/- 56 nmol/L, respectively). Basal plasma PL concentration was lower in the less than 0.5 mg/kg diet group only [60 nmol/L (measured in pooled samples), 190 +/- 73 and 235 +/- 63 nmol/L for less than 0.5, 3 and 6 mg/kg diet groups, respectively]. In both the less than 0.5 and 3 mg/kg diet groups, PLP clearance was lower than in control rats (0.158 +/- 0.025, 0.131 +/- 0.040 and 0.240 +/- 0.051 L.h-1.kg body weight-1, respectively). In the less than 0.5 mg/kg diet group, PLP synthesis was more efficient than in control animals (34.7 +/- 9.3, 12.1 +/- 2.5 and 16.7 +/- 11.4% for less than 0.5, 3 and 6 mg/kg diet groups, respectively). In both the less than 0.5 and 3 mg/kg diet groups, volume of distribution of PLP as well as of PL was larger than in controls. It is concluded that B-6 vitamer metabolism is influenced by vitamin B-6 status. The metabolic pathway involved (PLP synthesis and/or PLP degradation) was observed to depend on degree of vitamin B-6 deficiency. PMID- 1941182 TI - Lactose, calcium source and age affect calcium bioavailability in rats. AB - Calcium bioavailability was defined as either retention of 45Ca in tibias (Experiment 1) or retention of 47Ca in carcasses (Experiment 2). In Experiment 1, rats (age 21, 40 or 100 d) were fed purified meals extrinsically labeled with 45Ca. The meals contained either 0.5% Ca (control) or 1% Ca [control supplemented with CaCO3, calcium citrate-malate (CCM), milk or cheese] and either no lactose or 20% lactose. Lactose increased Ca bioavailability (P less than 0.05) from the control and milk meals in all age groups. Increases from CCM and CaCO3 were significantly only in the 21-d-old group. Lactose did not affect bioavailability from cheese. In Experiment 2, suckling rats (age 7, 12 or 17 d) were gavaged with 47Ca-labeled milk (fluid skim or lactose-hydrolyzed fluid skim) or an aqueous CaCl2-casein mixture (containing either no sugar, glucose + galactose, or lactose). Bioavailability from milk was higher than from lactose-hydrolyzed milk in all age groups. Lactose and glucose + galactose increased bioavailability over the sugar-free CaCl2-casein mixture in all age groups. Data from these experiments show that lactose enhances Ca bioavailability at several stages of development and the effect is not markedly diminished by high Ca diets. Lactose increases Ca bioavailability from a variety of sources but the magnitude of the effect may vary among sources. PMID- 1941183 TI - Dietary citrate and kidney function affect aluminum, zinc and iron utilization in rats. AB - Four studies were conducted to examine the effect of dietary citrate and calcium and modest reductions in kidney function on aluminum utilization in rats. Ingestion of citrate increased retention of aluminum in bones of rats fed 1 mg Al/g diet and increased apparent absorption of zinc. The increased retention of aluminum was not linearly related to dietary citrate levels. These data suggest that citrate had a general effect on the solubility of trace elements in the gut that promoted absorption. When dietary calcium intake was increased from 67 to 250 mumol/g diet, aluminum concentrations in bone were reduced without a change in growth of rats. A reduction (approximately 30%) in kidney function, which was insufficient to alter growth, increased aluminum retention in bone by 34% in rats injected with aluminum and by 13% in rats fed aluminum. Rats fed aluminum seemed to retain in tissues only 0.01 to 0.05% as much aluminum as those injected with aluminum. Thus, tissue concentrations of aluminum, and presumably toxicity, can be altered by moderate changes in diet and kidney function even though overall retention of orally administered aluminum is extremely low. PMID- 1941184 TI - Compromised zinc status in rats adversely affects calcium metabolism in platelets. AB - The effect of zinc status on external calcium uptake by rat platelets and the relation of uptake to aggregation malfunction were studied. For 11 d, immature male rats were fed either a low zinc diet (0.3 mg/kg) ad libitum, a zinc-adequate diet (100 mg/kg) ad libitum, or the adequate diet pair-fed. Washed platelets were loaded with fura-2 acetoxymethyl ester for measurement of cytosolic free calcium. The resting calcium concentration was higher in platelets from rats of low zinc status than in those from controls. When platelets were stimulated with a minimal level (0.12 mumol/L) of ADP, the free cytosolic calcium concentration increased to a greater extent when calcium was present in the external medium than in its absence. The difference was considered to be external uptake. Zinc status had no effect on internal release, but platelets from zinc-deficient rats took up significantly less external calcium. In conclusion, low zinc status in rats adversely affects calcium metabolism in platelets. Decreased uptake of external calcium by ADP-stimulated platelets is associated with defective aggregation. PMID- 1941185 TI - Human calcium absorption from whole-wheat products. AB - Fractional calcium absorption from wheat products and the influence of co ingested wheat products on calcium absorption from milk were measured in a series of randomized crossover studies in healthy adult women. The wheat had been intrinsically labeled with 45Ca during growth. In the first study, fractional calcium absorption from leavened whole-wheat bread averaged 0.817 +/- 0.124. By comparison, absorption from milk, ingested at a comparable load in the same women, averaged only 0.589 +/- 0.111. When labeled bread was co-ingested with milk, at the same aggregate load as for bread alone, bread calcium absorption fell to 0.748 +/- 0.103 (P less than 0.05). In a second study, calcium absorption from an extruded cereal prepared from intrinsically labeled wheat bran was compared with milk. Calcium absorption from the cereal (0.223 +/- 0.046) was significantly less than from milk (0.375 +/- 0.072) (P less than 0.001). When the two were co-fed at the same total load, milk calcium absorption fell to 0.258 +/- 0.055 (P less than 0.001). In a third study, the effect of phytate hydrolysis through yeast fermentation and of Maillard browning on calcium absorption was investigated using leavened bread and underbaked and overbaked cookies, each made with intrinsically labeled wheat flour. Calcium absorption from cookies was not affected by the extent of browning and averaged 0.652 +/- 0.087. However, calcium absorption from bread in these same women averaged 0.703 +/- 0.108. This was significantly more than from the cookies (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941186 TI - Phosphorus, but not calcium, affects manganese absorption and turnover in chicks. AB - Two balance studies with growing chicks were conducted to evaluate the effects of excess Ca or excess P on endogenous fecal Mn excretion and true Mn absorption. An isotope-dilution technique was used to estimate endogenous manganese in excreta. Supplements were added to a corn-soybean diet containing 1% Ca, 0.7% P (0.5% available P) and 37 mg Mn/kg. In Experiment 1, supplemental Ca levels of 0, 0.5 and 1.0% from feedgrade limestone were compared. True absorption of Mn was not affected by Ca level (P greater than 0.10) and averaged 2.8% for birds fed the Mn unsupplemented diet. In Experiment 2, a 2 x 3 factorial arrangement of treatments included: 100 and 1000 mg/kg supplemental Mn (from MnSO4.H2O) and 0, 0.4 and 0.8% added P supplied by dicalcium phosphate. Excess P significantly decreased true absorption of Mn (P less than 0.01). In birds fed 100 mg/kg supplemental Mn, absorption of Mn decreased 22% as excess P increased from 0 to 0.8%, whereas in birds fed 1000 mg/kg supplemental Mn, Mn absorption decreased 59% as a result of 0.8% P supplementation. These results confirm that the antagonism of Mn by inorganic P is due to reduced gut absorption of Mn. PMID- 1941188 TI - Energy restriction and the partitioning of energy among the costs of reproduction in rats in relation to growth of the progeny. AB - Compared with well-nourished controls, progeny of energy-restricted females are smaller and grow less well. The mechanisms behind these effects are frequently studied in rats but interpretation of such studies requires knowledge about the partitioning of dietary energy among the costs of reproduction and maternal needs. Energy partitioning was studied in rats fed ad libitum or 70% of ad libitum intake from 24-34 d before conception until d 14 of lactation and in virginal controls. Body composition was estimated for adult rats on d 1 of gestation, for adult rats and litters on d 1, 9 and 14 of lactation and for virginal controls after 65 d of dietary treatment. Milk production and composition were also studied. Dams in the two groups retained similar amounts of energy during pregnancy. Mobilized body energy corresponded to only 6 and 12% of the energy in milk for ad libitum-fed and restricted rats, respectively. Adult energy-restricted rats were smaller than their ad libitum-fed counterparts and thus needed less energy for maintenance. During lactation, energy-restricted rats used less energy per unit body size than ad libitum-fed rats. Pups of restricted dams were not only smaller, they also utilized milk energy less efficiently than did pups of well-fed dams. PMID- 1941187 TI - Absorption of short-chain fatty acids from the rat cecum in vivo. AB - Absorption of the short-chain fatty acids (SCFA), acetate, propionate and butyrate, was studied in vivo by measuring their disappearance from the washed cecum of anesthetized rats. The SCFA seemed to be absorbed predominantly by simple passive diffusion, because there was linear absorption over a wide concentration range, and no evidence of competition or enhancement of absorption when more than one SCFA was present in the lumen. Absorption of these three SCFA was independent of chain length. Their absorption was clearly limited by the lipid membrane, because permeability through the unstirred water layers was much greater than through the lipid membrane. Absorption was unaffected by altering the pH of the luminal infusate between 5.4 and 7.4. Based on our observation that, during absorption, there were increases in pH, total CO2 and HCO3- but no change in pCO2, we suggest that SCFA are absorbed primarily via diffusion involving anionic exchange with HCO3-. PMID- 1941189 TI - Dietary fat saturation affects glucose metabolism without affecting insulin receptor number and affinity in adipocytes from BHE rats. AB - The effects of dietary fat source on epididymal fat cell insulin receptor binding and affinity and on glucose transport and use by genetically diabetic rats were studied. Male BHE rats were fed 6% fat/64% sucrose diets. The fat consisted of 1% corn oil plus 5% beef tallow, menhaden oil or corn oil. Glucose tolerance was assessed at 100, 300 and 600 d of age. At 100 d of age the fat pads were excised, isolated adipocytes prepared and insulin receptor number, receptor affinity, 3-O methyl glucose uptake and glucose use determined. Insulin receptor number and binding affinity were not affected by dietary fat type. The transport and subsequent use of glucose were greater in fat cells from rats fed beef tallow compared with those from rats fed corn oil or menhaden oil. All three groups exhibited a deterioration in glucose tolerance with age. Although we observed greater glucose transport, oxidation and conversion to fatty acids in beef tallow fed rats, we saw no differences in these measurements between cells from corn or menhaden oil-fed rats. Thus, we conclude that the effects of these dietary lipids are attributable to effects of saturated fatty acids on intracellular events rather than on the insulin receptor per se, and that the type of unsaturated fatty acid [(n-3) vs. (n-6)] is of little importance to the regulation of glucose metabolism by isolated adipocytes. PMID- 1941190 TI - Dietary fat saturation affects hepatocyte insulin binding and glucose metabolism in BHE rats. AB - The influence of feeding 6% hydrogenated coconut oil, corn oil or menhaden oil on hepatocyte insulin binding, receptor number and glucose use was studied. Hepatocytes isolated from rats fed menhaden oil had a significantly greater affinity for insulin than hepatocytes from rats fed hydrogenated coconut oil. Glucose use was not influenced by diet; uniformly labeled glucose was metabolized to CO2 or to lipid similarly in cells isolated from rats fed the three oils. Thus, dietary fat type in a low fat diet influenced events at the plasma membrane without influencing intracellular events. PMID- 1941191 TI - The drug LY79771 affects fat regain by starved and refed BHE rats. AB - The effect of the drug LY79771 on the fat rebound response of BHE rats to starvation-refeeding was studied. Three experiments were conducted. Experiment 1 determined the effect of the drug on the composition of the regained weight following a period of starvation. The drug-treated rats had significantly less body fat after refeeding than did the control rats. Experiment 2 measured the liver and fat pad lipid levels and the activities of two NADP-linked enzymes after starvation-refeeding. The classic two- to threefold hepatic glucose-6 phosphate dehydrogenase and malic enzyme overshoot and increase in liver and fat pad lipid levels were seen in refed controls but not in refed LY79771-treated rats. Experiment 3 measured de novo fatty acid synthesis in LY79771-treated and control rats. Treatment with LY79771 resulted in lower hepatic fatty acid synthesis in starved and refed rats. These observations suggest that LY79771 can be effective in preventing fat regain following energy deprivation. PMID- 1941192 TI - Interpretation of nutrient-response relationships in rats. AB - Nutrient-response curves are nonlinear and, as is true of other curves that define the rates of biological reactions, these curves can be described by rational polynomials. These nutrient-response curves presumably reflect the metabolic fate of the nutrient. Data reported for the accumulation of body nitrogen in rats fed three different proteins are interpreted in terms of the biochemical systems theory and metabolic control theories. Analysis of the rational polynomials that define the nutrient-response curves permits partitioning the nutrient between a number of grossly defined metabolic pathways. The power law formalism of the biochemical systems theory is discussed with respect to the well-established relationship between body weight and basal energy requirement. PMID- 1941193 TI - Influence of intake of skim milk from cows immunized with intestinal bacterial antigens on onset of renal disease in (NZB x NZW)F1 mice fed ad libitum or restricted in energy intake. AB - Autoimmune disease-prone (NZB x NZW)F1 (B/W) female mice are a model of human lupus erythematosus. Immune milk, obtained from cows immunized with various intestinal bacterial antigens, was given to B/W mice as a component of diets beginning at 8 wk of age. Diets were fed ad libitum or restricted to 60% of ad libitum energy intake. Controls were fed commercial skim milk. In B/W mice fed ad libitum, the titers of anti-single-stranded DNA antibodies were significantly lower in immune milk-fed mice at 4 and 6 mo of age. Onset of proteinuria was delayed and life span was significantly prolonged by immune milk feeding. Surface phenotypes of the T cells and levels of the responsiveness of lymphocytes to mitogens were not changed by immune milk feeding. The B/W mice restricted to 60% of ad libitum energy intake, which preserved immune responsiveness, had not developed proteinuria by 14 mo of age, irrespective of immune milk feeding or control milk feeding. However, at 10 mo of age, the level of plasma antibodies against intestinal bacteria was significantly higher in energy-restricted mice fed control milk than in those fed immune milk or in mice fed ad libitum. PMID- 1941194 TI - Iron supplementation increases gentamicin nephrotoxicity in rats. AB - Gentamicin (GM), an aminoglycoside antibiotic, can cause acute renal failure in humans and experimental animals. It has been proposed that lipid peroxidation may play a role in GM nephrotoxicity. Nutrients such as copper, selenium or iron that influence lipid peroxidation may also be a factor in toxicity. This study investigated the effect of supplemental dietary iron on the nephrotoxicity of GM. Weanling male Sprague-Dawley rats were fed control [0.75 mmol (42 mg) iron/kg] or iron-supplemented [4.32 mmol (242 mg) iron/kg] diets for 3 wk. Rats were subsequently injected intraperitoneally with GM (50 or 100 mg.kg body wt-1.d-1) or saline for 8 d. High dietary iron resulted in greater sensitivity to GM (100 mg/kg body wt) toxicity in terms of elevated urinary excretion of n-acetyl-beta glucosaminidase (NAG) and increased mineralization, casts and megalocytes in renal tubules. After GM treatment was terminated, NAG excretion decreased with both dietary treatments. However, renal tubular cell damage, due to GM, remained higher than in saline-treated controls in rats fed 4.32 mmol iron/kg diet. PMID- 1941195 TI - The effect of diet, exercise and 7,12-dimethylbenz(a)anthracene on food intake, body composition and carcass energy levels in virgin female BALB/c mice. AB - This study investigated the effect of diet, exercise and , 7,12 dimethylbenz(a)anthracene (DMBA), a mammary-tumor carcinogen, on food intake, energy consumption, body weight and body composition in virgin female BALB/c mice. Interactions were examined among three diet conditions (standard AIN-76A, restricted AIN-76A and high fat AIN-76A diet), two exercise conditions (with and without treadmill exercise) and two treatment conditions (carcinogen or corn oil sham). Mice were randomized to one of 12 groups at 6 wk of age; beginning at 8 wk of age, all mice received either 7,12-dimethylbenz(a)anthracene (1 mg/0.2 mL corn oil) or 0.2 mL of corn oil via gastric tube once each week for six consecutive weeks. Exercise in a rotating-drum treadmill was initiated at 10 wk of age and was increased to a final rate of 6 m/min for 60 min, 5 d/wk. Mice were killed at 24 wk of age, confirmed to be tumor-free and analyzed for protein and fat content, from which body energy was calculated. Energy consumption was highest in the standard diet-fed groups followed by the high fat diet-fed groups and the restricted diet-fed groups. The groups fed the standard diet and restricted diet had similar body weight and carcass energy. Exercise or DMBA treatment generally reduced food consumption, energy intake, body weight and carcass energy. In summary, diet, exercise and DMBA all had pronounced effects on energy consumption, which in turn affected body composition. These treatments may influence expression of breast cancer via their effects on body composition. PMID- 1941196 TI - Reduced energy intake and moderate exercise reduce mammary tumor incidence in virgin female BALB/c mice treated with 7,12-dimethylbenz(a)anthracene. AB - This study evaluated the concurrent effects of diet (standard AIN-76A, restricted AIN-76A and high-fat diet) and moderate rotating-drum treadmill exercise on the incidence of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in virgin female BALB/cMed mice free of murine mammary tumor virus. Exercise significantly reduced food consumption in the groups fed the standard diet and high fat diet. Although food consumption varied widely, final body weight was similar in all groups. Exercise had no effect on mammary tumor incidence in the standard diet fed groups (without exercise, 47%; with exercise, 45%); however, exercise reduced mammary tumor incidence in the other groups as follows: restricted diet/no exercise, 28%; restricted diet/with exercise, 13%; high fat diet/no exercise, 31%; high fat diet/with exercise, 19%. Restricting food intake reduced mammary tumor incidence, but had no effect on body weight. Although energy intake was related to mammary tumor incidence, neither body weight nor dietary fat predicted tumor incidence. PMID- 1941197 TI - History of nutrition: history and current status of research in human energy metabolism. PMID- 1941198 TI - Assumptions used in measurements of energy metabolism. AB - The knowledge that the chemical burning of nutrients and the oxidation of nutrients in animals were similar energy-releasing processes laid the foundations for the study of energy metabolism by direct and indirect calorimetry. The early development of calorimetry and its pioneers will be reviewed. PMID- 1941199 TI - The measurement of energy expenditure. AB - This is a brief account of the development of energy expenditure measurements, from speculations by early philosophers on the nature of the "innate fire," through the beginnings of quantitative animal calorimetry and to the combined material and energy balances of Rubner and of Atwater and Benedict, which established the science of nutritional energy. The equivalence of oxidation rate and heat loss led to the simplification of indirect calorimetry, followed by the era of studies of basal metabolic rate. Current practices are reviewed for measuring energy expenditure by indirect calorimetry (respiration chambers, ventilated hoods, doubly labeled water) and direct calorimetry (rooms, suits). Because problems remain in the exact account of energy balance during weight change, growth, pregnancy and exercise, perhaps it may be time to combine once again carbon balance with energy balance, using modern methods. PMID- 1941200 TI - Thermodynamics and living systems: problems and paradigms. AB - The utility of thermodynamic laws in biological systems is reviewed. The joint historical development of thermodynamics and of respiratory physiology in the 19th century is surveyed. From first principles of thermodynamics, problems are noted in their application to physiological calorimetry. PMID- 1941201 TI - Practical estimates of energy requirements. AB - The scientific genealogy of those who studied human energy expenditure is reviewed. The genealogic review is followed by a discussion of the basal metabolic rate as the basis for calculations of energy requirements in humans. PMID- 1941202 TI - Contribution of the dog to the science of nutrition. AB - In the 19th century when the basic principles of nutrition were established, the main work was done first in France and then in Germany. In each country dogs were the overwhelming choice as the model experimental animal. In France the complexity of nutritional requirements first came to be appreciated and the inadequacy of gelatin as a substitute for muscle protein was identified. In Germany quantitative balance procedures for nutrients were developed and it was shown that balance could be achieved at many levels after a period of adaptation. In the U.S.A. at the beginning of this century, Russell Chittenden showed that dogs could do well when fed low protein diets so long as they contained some nonprotein factors that were provided by meat and milk. On the basis of that work Joseph Goldberger developed a diet which produced a condition analogous to pellagra in dogs. This led to the discovery that yeast was a potent preventive of the disease and to the eventual identification of niacin as the primary active factor. Work in Britain with dogs as models for experimental rickets gave apparently conflicting results, with either environmental or dietary changes apparently protecting from the disease. Further work showed that calciferol could be obtained either by irradiation of the skin or by the consumption of another animal's store. Lastly, Edward Mellanby's continued work on the rachitic effect of cereals led to the spin-off finding that wheat flour improved with nitrogen chloride, although nontoxic to rats, was responsible for the problem of canine hysteria in dogs that had developed in the 1930s and 1940s. Its use by millers was than banned. PMID- 1941203 TI - Growth and skeletal development in Great Dane pups fed different levels of protein intake. AB - Feeding a dog of a large breed with a diet exceeding the National Research Council (1974) recommendations for energy, protein, calcium, phosphorus and vitamin D may result in disturbances of skeletal development. The effects of excess energy and various calcium:phosphorous ratios per se have been reported by others. The role of dietary protein, especially with regard to calcium metabolism and skeletal development, in large breed-dogs is reported in this article. Seventeen Great Dane pups, 7 wk of age, were divided into three groups. During 18 wk each group received isoenergetic dry food (approximately 15 kJ metabolizable energy/g) containing 31.6, 23.1 or 14.6% protein on dry matter basis. No differences were found among the high (H-Pr), normal (N-Pr) and low protein (L Pr) groups for the height at the shoulder. Significant differences were found between the H-Pr and L-Pr groups for body weight and plasma albumin and among all three groups for plasma urea. The differences in protein intake per se had no demonstrable consequences for calcium metabolism and skeletal development. A causative role for dietary protein in the development of osteochondrosis in dogs is unlikely. PMID- 1941204 TI - Relationship between nutrition and bone growth in large and giant dogs. AB - The pathogenesis of the osteochondrosis syndrome was studied in large and giant breeds of dogs. Spontaneous cases of osteochondrosis were examined in large breed dogs, and experimental disease was investigated in Great Dane puppies fed ad libitum or restricted diets until 6 mo of age. This investigation concluded that the primary lesion occurring in osteochondrosis of dogs from the large and giant breeds is an acquired pattern of osteopenic and biomechanically weak subchondral spongiosa that cannot provide adequate bony support for the articular cartilage of joints. Excessive biomechanical loading of the inadequately supported epiphyseal articular cartilage leads to secondary disturbances in the nutrition, metabolism, function and viability of the chondrocytes in the developing joint surface. The primary lesion in the subchondral spongiosa develops when overnutrition (ad libitum feeding) overstimulates skeletal growth and cancellous bone remodelling mechanisms in those breeds of dogs who already have an inherent capacity for rapid skeletal growth. The epiphyseal spongiosa of rapidly growing dogs of the larger breeds is inherently less dense and less strong per unit area than epiphyseal spongiosa of dogs from the smaller breeds. Overnutrition in dogs from the larger breeds exaggerates this tendency to create osteopenia by increasing the rates of skeletal growth and remodeling of the newly formed cancellous bone. Accelerated rates of bone growth and bone remodeling act in concert to product a pattern of epiphyseal spongiosa that is composed of fine trabecular systems that are spaced relatively far apart and that are ultimately less strong per unit area than in small breeds of dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941206 TI - Role of diet in the progression of chronic renal failure: experience with human studies and proposed mechanisms by which nutrients may retard progression. PMID- 1941205 TI - Body composition of cats as a basis for factorial calculation of energy and nutrient requirements for growth. PMID- 1941207 TI - Dietary protein intake and the glomerular adaptations to partial nephrectomy in dogs. AB - After partial nephrectomy (Nx) in rats, a temporal pattern of progressively declining renal function often develops. This pattern has been attributed to the development of glomerular hyperfiltration, hypertension and hypertrophy in remnant nephrons. In rats, dietary protein restriction prevents these adaptive changes in remnant nephrons, thereby preserving renal structure and function. However, long-term studies of the temporal pattern of renal function have failed to identify a consistently progressive deterioration of renal function in partially Nx dogs, and a protective effect of protein restriction has not been apparent in this species. To address these issues in dogs, we evaluated the single nephron adaptations to partial Nx in dogs and the effect of dietary protein restriction on these adaptations. Results of our micropuncture studies in partially Nx dogs indicate that remnant nephrons of dogs exhibit glomerular hyperfiltration (single nephron glomerular filtration rate of 144 +/- 8 vs. 71 +/ 4 nL/min in controls, P less than 0.05), hypertension (glomerular capillary pressure of 75.1 +/- 1.6 vs. 63.2 +/- 1.9 mmHg in controls) and hypertrophy (glomerular volume of 3.54 +/- 0.24 x 10(6) vs. 2.04 +/- 0.05 x 10(6) microns3 in controls, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941208 TI - Influence of dietary protein on renal function in dogs. AB - Two previously published studies in dogs with reduced renal function are reviewed. In the first study, renal function and biochemical responses to dietary changes were studied in four dogs with stable chronic renal failure. The objective was to determine if dogs with moderate stable failure adjust to diets with varied protein and electrolyte content. These dogs were found to have the capacity to adapt to a wide range of dietary protein and electrolyte intake. The only exception was found in dogs fed a reduced-protein diet, which failed to appropriately adjust renal tubular excretion of sodium and phosphate. The only advantage of reduced dietary protein in this study was a reduction in blood urea nitrogen (BUN). Disadvantages of reduced-protein diets were reduced glomerular filtration rate (GFR) and renal plasma flow. In the second study, the hypothesis that large amounts of dietary protein sustain renal hyperfunction and produce progressive glomerulosclerosis in dogs as previously reported in rats was tested. Results failed to find a pattern of deterioration of renal function over 4 y. Light microscopic changes and electron microscopy also failed to find glomerular injury similar to that reported in rodents. These results do not support the hypothesis that feeding a high protein diet had a significant adverse effect on renal function or morphology. PMID- 1941209 TI - Effect of modified protein diets in dogs and cats with chronic renal failure: current status. AB - Studies in rodents indicate that diet influences progression of renal failure. Excessive dietary intakes of protein, fat, energy and phosphorus have been implicated in promoting progression of renal failure, while restriction of some or all of these dietary constituents limits progressive renal injury. Studies confirm that renal failure is progressive in some dogs with moderate-to-advanced renal dysfunction. Recent studies also indicate that unrestricted intakes of protein promotes proteinuria in dogs and cats and glomerular injury in cats. PMID- 1941210 TI - Effects of medium protein diets in dogs with chronic renal failure. AB - To study dietary management of chronic renal failure (CRF), 1600 dogs older than 5 y were screened for serum urea and serum creatinine concentration. Three hundred fifty-eight dogs (22.4%) showed values above normal (6.67 mmol/L of serum urea, 88.4 mul/L of serum creatinine). Sixty of these dogs with slight or moderate clinical signs of CRF, at least polyuria, were selected for the study. Thirty-two dogs were fed a commercial canned medium protein diet (MPD) [27% protein, 0.36% phosphorus in dry matter (DM)] and 28 dogs were fed a homemade diet (HMD; 21.5% protein, 0.38% phosphorus in DM). Dogs were reevaluated for clinical status, blood chemistry profile (urea, creatinine, total protein, calcium and phosphorus) and urinalysis at 9 intervals over 28 wk. In general, palatability of both diets was high and dogs maintained their body weight. Nevertheless eight dogs of the MPD and six dogs of the HMD group died or had to be killed during the study. In surviving dogs, serum urea, creatinine, phosphorus and [P x Ca] were significantly reduced nearly to the normal range after 4 wk. A slight increase at the end of the study occurred because clients did not adhere strictly to dietary instruction after recovery of the dogs. These results suggest that elderly dogs frequently show a mild or moderate CRF, and dietary treatment with medium protein and low phosphorus diets is effective in improving blood chemistry data as well as physical condition of those dogs. PMID- 1941211 TI - Abnormal intestinal permeability could play a role in the development of gluten sensitive enteropathy in Irish setter dogs. PMID- 1941212 TI - Delayed introduction of dietary cereal may modulate the development of gluten sensitive enteropathy in Irish setter dogs. PMID- 1941214 TI - Body condition and energy intakes of dogs in a referral teaching hospital. PMID- 1941213 TI - Dietary management of idiopathic feline hepatic lipidosis with a liquid diet supplemented with citrulline and choline. PMID- 1941215 TI - Occurrence of ascites abdominalis in dogs. PMID- 1941216 TI - Safety of ethoxyquin in dog foods. PMID- 1941217 TI - Dietary taurine and feline reproduction and development. AB - The reproductive performance of female cats is severely affected by dietary taurine deficiency resulting in excessive reproductive wastage, including frequently resorbed or aborted fetuses and stillborn or low birth-weight live kittens. These studies were performed using female cats fed a completely defined purified diet (taurine-free) alone or supplemented with taurine for greater than or equal to 6 mo before mating, and their breeding performance was monitored for several years. Diets containing 0, 0.005 or 0.01% taurine produced severe taurine depletion and poor reproductive performance. Those containing 0.05, 0.2 or 1% taurine resulted in no apparent abnormalities and a normal breeding performance. A diet containing 0.02% taurine resulted in no apparent abnormalities and a normal breeding performance. A diet containing 0.02% taurine resulted in modest taurine depletion and a partially compromised reproductive performance. Kittens from taurine-deficient mothers have a poor survival rate and grow at a slower rate than kittens from females fed an adequate taurine diet. The brain weights of kittens from taurine-deficient mothers are significantly smaller than normal, both at birth and at weaning at 8 wk. Surviving kittens exhibit a number of abnormalities. The differences in maternal dietary taurine are reflected in the taurine concentrations found in the milk of lactating females. Our results strongly suggest that a certain amount of taurine is mandatory for survival and normal development in the cat. PMID- 1941218 TI - Plasma taurine levels in healthy cats and cats with cardiac disorders. PMID- 1941219 TI - Gender and dietary amino acid supplementation influence the plasma and whole blood taurine status of taurine-depleted cats. PMID- 1941220 TI - Influence of taurine intake on plasma taurine values and renal taurine excretion of cats. PMID- 1941221 TI - Effect of meal-feeding and food deprivation on plasma and whole blood taurine concentrations in cats. PMID- 1941222 TI - Feline plasma and whole blood taurine levels as influenced by commercial dry and canned diets. PMID- 1941224 TI - Effect of dietary protein and taurine on enzyme activities involved in cysteine metabolism in cat tissues. PMID- 1941223 TI - Dogs large and small: the allometry of energy requirements within a single species. AB - Dogs are unique among mammals in having a 100-fold range in body weight for nonobese adults. This variation makes the calculation of the power function for metabolic body size and hence the allometry of energy requirements a particularly challenging subject. Several functions have been proposed from W0.68 to W0.88 (W = body weight in kg). In the present study we measured the heat output of 22 dogs representing seven breeds, aged 1-10 y with W from 5.8 to 48.8 kg, using a whole body calorimeter specifically designed for this purpose. Regression of log energy output against log W gave the equation 678 W0.64 (r = 0.96; P less than 0.001), which is considered to represent resting energy expenditure (REE) as kJ/d. If estimates of the energy cost of activity are added to REE, new equations of 655 W0.69 (low activity) and 643 W0.73 (higher activity) are obtained, depending on the amount of activity included in the calculation. From these results we suggest that the allometry of energy requirements of adult dogs is a function of different exponents for REE and the energy cost of activity. It does not appear to exceed W0.75 and may be nearer to W0.67. PMID- 1941225 TI - The nutrition of the budgerigar (Melopsittacus undulatus). AB - Growing interest in the nutrition of the budgerigar (Melopsittacus undulatus) has highlighted the paucity of knowledge in this area. The aims of this study were to review the available literature on their individual nutrient requirements and relate this to the nutrient content of their predominantly seed-based diet and to investigate the effect of the bird's daily energy requirement on the fluctuations in body weight. Studies were conducted at the Waltham Centre to measure the relationship between daily metabolizable energy intake (kJ/kg BW) and body weight change (g/d) for groups of adult budgerigars. The birds were found to require daily 48-128 kJ/bird depending on their body mass (birds in our colony typically weigh 30-80 g). During a series of breeding trials the daily energy intake for a breeding pair plus their three chicks, at peak energy intake, was found to be 483 505 kJ (at pairing, the mean daily energy intake of the breeding pairs was 231 kJ). Apparent metabolizability of the major nutrients from a seed diet were generally found to be greater than 80%, which allows these birds to assimilate the high levels of energy needed for their basal metabolism. In summary, the nutrient requirements of the budgerigar (where known) were found to be similar to those of other avian species, however, further work is needed, especially in the area of availability of key nutrients. Further developments in the dietary management of these birds will only be possible if researchers can overcome the birds' poor acceptance of novel foods and satisfy their high basal energy requirements before establishing their requirements for individual nutrients. PMID- 1941226 TI - Formulated diets versus seed mixtures for psittacines. AB - Psittacines are often classified as seed eaters despite studies that have established great diversity in food habits in the wild. While seeds are consumed, so are flowers, buds, leaves, fruits and cambium. Some psittacines consume part of greater than 80 species of grasses, forbs, shrubs and trees. In addition, insects may be important. Although there are few controlled studies of the requirements of psittacines, it is probable that most nutrient needs are comparable to those of domesticated precocial birds that have been thoroughly studied. Commercial seed mixes for psittacines commonly contain corn, sunflower, safflower, pumpkin and squash seeds, wheat, peanuts, millet, oat groats and buckwheat, although other seeds may be present. Because hulls/shells comprise 18 69% of these seeds and they are removed before swallowing, a significant proportion of typical seed mixtures is waste. Some of the seeds also are very high in fat and promote obesity. Common nutrient deficiencies of decorticated seeds include lysine, calcium, available phosphorus, sodium, manganese, zinc, iron, iodine, selenium, vitamins A, D, E and K, riboflavin, pantothenic acid, available niacin, vitamin B-12 and choline. Attempts to correct these deficiencies by incorporating pellets into seed mixes are usually thwarted by rejection of the pellets and disproportionate consumption of items that are more highly favored. An extruded diet formulated to meet the projected nutrient needs of psittacines was fed with fruits and vegetables to eight species of psittacines for 1 y. Fledging percentage was increased to 90% from the 66% observed during the previous 2 y when these psittacines were fed seeds, fruits and vegetables. Although this extruded diet was well accepted in a mixture of fruits and vegetables and met nutrient needs, analyses have shown that not all commercial formulated diets are of equal merit. PMID- 1941227 TI - Basic data for factorial derivation of energy and nutrient requirements of growing canaries. PMID- 1941228 TI - Intoxication in canaries due to endrin-contaminated feedstuff. PMID- 1941229 TI - Evaluation of the energy requirements of adult kennel dogs. AB - The objective of this experiment was to compare the energy requirements of healthy adult kennel dogs to those recommended by the National Research Council (NRC). The energy requirements of six beagles, six Siberian huskies and six Labrador retrievers were determined over a 54-wk period. Dogs were housed in groups of three in heated indoor-outdoor runs and fed a complete and balanced commercial dry dog food. Beagles had an average daily energy intake of 3414 kJ/dog with monthly averages ranging from 3146 to 3740 kJ/dog. Siberian huskies had an average daily energy intake of 5021 kJ/dog. Average monthly energy intakes ranged from 4715 to 5238 kJ/dog. Labrador retrievers had an average daily intake of 5611 kJ/dog with monthly averages ranging from 5063 to 6623 kJ/dog. Seasonal variation appeared to affect the breeds differently, with long-haired Siberian huskies showing less seasonal variation than the shorter-haired breeds. For all dogs energy intake (kJ/kg body weight 0.75) declined with age. The energy intake of each group of dogs was considerably below that recommended by the NRC. The reason for this discrepancy is unknown, although these data suggest that environmental conditions, breed and/or age play an important role. PMID- 1941230 TI - Energy requirements for maintenance and growth of wild mammals, birds and reptiles in captivity. AB - A wide range of wild animals are maintained in captivity as pets and an increasing number are likely to become dependent on captive breeding for conservation. Generally, these animals are fed ad libitum and a knowledge of their energy requirements is not essential. However, estimates of energy requirements are helpful in several situations: treating obesity, providing nutritional support to anorexic animals and feeding neonates. Data on basal metabolic rates (BMR) are available for approximately 5% of avian and 17% of mammalian species, and the maintenance requirement can be estimated at twice BMR. Estimates for other species can be based on allometric equations relating energy expenditure to body weight in the species that have been studied. Although between species time taken to grow increases with adult mass, wide variation remains after the effect of adult mass is considered. A model is developed which illustrates the impact of variation in time taken to grow on daily growth rate (per metabolic mass) at all stages of maturity. This model may assist in estimating the lower limit to energy requirements during growth. PMID- 1941231 TI - Energy requirements of growing Great Danes. PMID- 1941232 TI - Energy requirement for maintenance of adult dogs. PMID- 1941233 TI - Maintenance energy requirement of dogs: what is the correct value for the calculation of metabolic body weight in dogs? PMID- 1941234 TI - Nutrition of old dogs. PMID- 1941235 TI - Energy requirements of the queen during lactation and kittens from birth to 12 weeks. PMID- 1941236 TI - Digestible energy requirements of adult cats at maintenance. PMID- 1941237 TI - Use of ultrasound in the measurement of subcutaneous fat and prediction of total body fat in dogs. AB - An ultrasonographic unit (A-scan mode) has been evaluated as a noninvasive method for estimating body fat in 25 dogs. Six anatomical sites were defined and subcutaneous fat thickness was measured by means of ultrasound and histology. Total body fat was subsequently calculated in 12 dogs. There was a high correlation between histology and ultrasound for the measurement of subcutaneous fat (r = 0.81; P less than 0.001). Total body fat was successfully predicted using measurements taken with ultrasound at the lumbar area (r = 0.87; P less than 0.001). Measurements of subcutaneous fat thickness from other anatomical sites did not estimate body fat with the same accuracy. These results suggest that ultrasound can reliably measure subcutaneous fat in dogs and that these measurements, when taken from the mid lumbar area, can be used to predict total body fat. PMID- 1941238 TI - Investigations on palatability, digestibility and tolerance of low digestible food components in cats. PMID- 1941239 TI - Body condition and diet of relatively healthy older dogs. PMID- 1941240 TI - Effect of portosystemic shunting on nitrogen retention of dogs. PMID- 1941241 TI - Amino acid composition and digestibility of four protein sources for dogs. PMID- 1941242 TI - Effects of 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol in dogs with impaired renal function. PMID- 1941243 TI - Biotin deficiency in cats as induced by feeding a purified diet containing egg white. PMID- 1941244 TI - Role of the pancreas in the absorption and malabsorption of cobalamin (vitamin B 12) in dogs. PMID- 1941246 TI - Body mass, maintenance and basal metabolism in dogs. AB - Basal metabolism and body mass are related by the metabolic power function: P = aMb, where P = basal metabolism in Watts, a = mass coefficient, M = body mass in kg, and b = mass exponent. The mass exponent of 117 dogs from the literature b dog = 0.885 +/- 0.024 (r = 0.960; F = 1387; df = 1,115). This mass exponent is significantly greater than the commonly accepted value of 0.75 for mammals. The dog's 95% confidence ellipse is compared with that of mammals with body mass (M) less than 3.2 kg (the lower limit of the mass range in dogs) and greater than 3.2 kg. When M greater than 3.2 kg the interspecific metabolic mass exponent (bi) in mammals is also significantly greater than 0.75 and not different from b dog (bi = 0.869 +/- 0.034; r = 0.919; F = 648; df = 1,120). In mammals M less than 3.2 kg bi is significantly smaller than 0.75 (bi = 0.634 +/- 0.010; r = 0.941; F = 4319; df = 1,561). These data show that in mammals the relationship between the logarithms of basal metabolism and body mass is not accurately described by a single regression line. They also indicate that the commonly accepted 0.75 mass exponent is not applicable to the prediction of basal metabolism in dogs and mammals. The relationship between body mass and maintenance energy metabolism (MEM) in 332 dogs shows that the prediction interval is too wide to reasonably predict MEM in individual dogs. However, the minimum maintenance energy metabolism (MMEM in Watts) can be accurately predicted by a simple algorithm: MMEM = 10.3 + 1.41 x M. The theoretical meaning of the basal metabolic power function is discussed. PMID- 1941245 TI - Effects of two levels of zinc intake on growth and trace element status in Labrador puppies. PMID- 1941247 TI - Zinc, copper, iron and calcium concentrations in bitch milk. PMID- 1941248 TI - Investigations on copper deficiency in growing dogs. PMID- 1941249 TI - An alternative method for the collection of urine and feces and its application in measuring urinary mineral excretion in cats fed diets containing various amounts of phosphorus. PMID- 1941250 TI - Influence of food composition on the urine pH in cats. PMID- 1941251 TI - Effect of low potassium commercial nonpurified diet on renal function of adult cats. PMID- 1941253 TI - Intracellular cations: out of sight, out of mind? PMID- 1941252 TI - Effect of macromineral composition of diets on blood acid-base equilibrium and urinary acidity in dogs. PMID- 1941254 TI - Calcium metabolism in Great Dane dogs fed diets with various calcium and phosphorus levels. AB - The influence of dietary calcium on calcium metabolism was investigated in growing dogs that reach an adult body weight similar to that of humans. Seven groups of dogs (n greater than or equal to 5) were raised on a diet with a composition meeting the National Research Council (NRC) requirements (1974), but differing in calcium content, with or without a constant ratio to phosphorus. Control dogs fed 1.1% calcium and 0.9% phosphorus (all on a dry matter basis) were fed ad libitum (n = 10) or in restricted amounts (n = 6); dogs fed high calcium (3.3%) diets received either 0.9% phosphorus (n = 6) or 3.0% phosphorus (n = 6); dogs fed low calcium (0.55%) diets received either 0.9% phosphorus (n = 5 + 6) or 0.5% phosphorus (n = 8). Food intake, circulating total calcium and inorganic phosphorus concentrations and calcium metabolism, with 45Ca kinetics, were studied at 8, 14, 20 and 26 wk of age. Except for the difference in food intake in two groups at 14 wk (i.e., 0.55% calcium-0.9% phosphorus higher and 3.3% calcium-0.9% phosphorus lower, respectively, than the controls) no differences were noticed during the rest of the study. The mean plasma calcium concentrations did not differ between groups during the studies, whereas that of inorganic phosphorus revealed temporal aberrations in two groups. An absorption coefficient alpha of 45-66% was found for the control group. High and low calcium diets gave rise to values of 23-43% and 70-97%, respectively, for alpha irrespective of the phosphorus content of the diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941255 TI - Maternal dietary fat type influences the growth and fatty acid composition of newborn and weanling rats. AB - To determine whether the long-term consumption of different amounts or types of fat by female rats affects the growth and development of their progeny, Wistar rats were fed from weaning either a low fat diet (4.5% by weight) or one of three high fat (32%) diets containing predominantly beef tallow (high saturated fat), corn oil (high polyunsaturated fat) or equal portions of tallow and corn oil (high mixed fat). Offspring were killed at birth or weaning. Weight of newborn pups was lower with maternal consumption of high polyunsaturated fat diets. Carcass composition of newborn pups and body weight of weanling rats was unaffected by maternal diet. The percentage of carcass lipid was greater in weanling rats from all high fat-fed dams. In both newborn pups and weanling rats, percent composition in carcass lipids of 16:0, 16:1 and 18:1 fatty acids generally decreased and 18:2 increased as the high fat maternal diet became more unsaturated. The consumption of diets high in polyunsaturated fatty acids prior to and throughout gestation thus seemed to have a transitory effect on reducing fetal growth in rats. PMID- 1941257 TI - Dietary excesses of leucine influence growth and body composition of rainbow trout. AB - This study examined the hypothesis that a diet containing excess leucine may promote protein deposition in the body of rainbow trout. Diets were formulated with wheat germ meal and crystalline amino acids as major nitrogen sources. In Experiment 1, diets containing 1.1, 1.5, 2.2, 2.7, 3.5, 4.5, 6.0 and 6.5% leucine in wheat germ meal-crystalline amino acid diets were fed to fingerling rainbow trout. Diets containing up to 6.5% leucine did not inhibit weight gain or food intake. Body protein concentration tended to decrease as dietary leucine increased. In Experiment 2, fish were fed similar diets containing 3.3, 6.2, 9.2 and 13.4% leucine. After 10-11 wk of feeding, gross lesions including scoliosis, deformed opercula, scale deformities, scale loss, spongiosis of epidermal cells and scale regeneration were observed in 20% of the fish fed diets containing 13.4% leucine. High dietary leucine did not depress plasma valine or isoleucine concentrations. Therefore, the gross lesions could be attributed to a toxic effect of excess dietary leucine. Polyamine concentrations, which were used as a metabolic indicator for growth, were not significantly different in the tissues of fish receiving different treatments, thus supporting the hypothesis that increasing dietary leucine did not increase body protein deposition. PMID- 1941256 TI - High levels of the (n-6) fatty acid 4,7,10,13,16-docosapentaenoate in the retinas of rabbits are reduced by feeding dietary fish oil from birth to adult life. AB - High levels of 4,7,10,13,16-docosapentaenoic acid [22:5(n-6)], a fatty acid usually associated with (n-3) fatty acid deficiency, have been reported in the retina of young rabbits. We studied the fatty acid composition of the rabbit retina throughout development, from birth to adult life. We also attempted to modify the fatty acid composition of the retina by the feeding of fish oil, high in docosahexaenoic acid [22:6(n-3), DHA]. Female rabbits were fed either a control or 2% fish oil diet through pregnancy and the nursing period. Weaned rabbits received the mothers' diet. In the retinas of control rabbits, 22:5(n-6) represented 3.7% of total fatty acids at birth, reached 15.1% at 9 wk and declined to 5.6% in adult rabbits. However, 22:6(n-3) increased steadily from birth onwards, from 3.8% of total fatty acids at birth to 19.6% in adults. Dietary fish oil increased the trace concentrations of long-chain (n-3) fatty acids in the milk to 10% of total fatty acids, reduced retinal 22:5(n-6) to less than or equal to 0.5% at all ages, and increased DHA to approximately 30% by 9 wk. Retinal phosphatidylethanolamine was even more sensitive to the impact of the fish oil diet, with DHA levels in newborn rabbits rising from 10% (control diet) to 43% of total fatty acids. These results demonstrated that 22:5(n-6) in the normal rabbit retina remains elevated (compared with other species) at all ages even as retinal DHA increases. The great increase of DHA in newborns whose mothers were fed fish oil suggests placental transfer of DHA and incorporation into retinal lipids. PMID- 1941258 TI - Vitamin B-12 deficiency increases the specific activities of rat liver NADH- and NADPH-linked aquacobalamin reductase isozymes involved in coenzyme synthesis. AB - Rat liver contains both NADH- and NADPH-linked aquacobalamin reductases, which are involved in the synthesis of the vitamin B-12 coenzymes and are distributed in both the mitochondrial and microsomal membranes. To clarify the physiological roles of these hepatic enzymes, vitamin B-12-deficient rats were used to study the effect of the deficiency on the enzyme activities. Male rats fed a vitamin B 12-deficient diet for 11 wk developed a severe vitamin B-12 deficiency with a high urinary methylmalonate excretion (214.3 +/- 115.2 mumol/d) and approximately 96% lower hepatic vitamin B-12 content. Tissues of the vitamin B-12-deficient rats were assayed for NADH- and NADPH-linked aquacobalamin reductase activities. The specific activities of both enzymes in homogenates of liver, kidney or upper intestine were shown to be three- to 20-fold greater in the vitamin-deficient rats than in the control rats. In liver, the vitamin deficiency specifically elevated the specific activities of the mitochondrial NADH-linked and microsomal NADPH-linked enzymes. These are likely the isozymes involved in vitamin B-12 coenzyme synthesis. PMID- 1941260 TI - Mitogen response of B cells, but not T cells, is impaired in adult vitamin A deficient rats. AB - The effect of vitamin A deficiency on the mitogen response of splenic B and T lymphocytes was determined in adult vitamin A-deficient rats. Female weanling Brown Norway/Billingham-Rijswijk (BN/BiRij) and Sprague-Dawley rats were fed a semipurified, essentially vitamin A-free diet, which resulted in clinical symptoms of vitamin A deficiency and severely decreased plasma retinol contents at the age of about 17 and 41 wk for BN/BiRij and Sprague-Dawley rats, respectively. A lower B cell proliferative response after stimulation with lipopolysaccharide in combination with dextran sulfate was observed in vitamin A deficient rats of both strains, but the T cell proliferative response after concanavalin A stimulation was unchanged. The lower B cell mitogen response was not associated with changes in the cellular composition of the spleen (as analyzed with monoclonal antibodies specific for the various subsets of T and B cells and of macrophages). We suggest that the age at which clinical symptoms of vitamin A deficiency are induced may be an important determinant for the immunological variables affected. PMID- 1941259 TI - Bacterially synthesized folate in rat large intestine is incorporated into host tissue folyl polyglutamates. AB - Unlike mammalian tissues, certain intestinal microflora are capable of de novo synthesis of folate. To explore the availability of bacterially synthesized folate to the host organism, we used [3H] p-aminobenzoic acid (3H PABA) to label folate newly synthesized by the intestinal microflora. Labeled folates were isolated by affinity chromatography and identified by ion-pair HPLC. In this study [3H]PABA was injected into rat cecum to determine whether the [3H]folate synthesized by bacteria appeared in rat liver and other tissues. Rats were kept in sling suits to prevent coprophagy. Ion-pair chromatography of the purified liver folate demonstrated that bacterially derived [3H]folate was incorporated into all host liver-specific folate polyglutamates, mostly penta- and hexaglutamyl derivatives. Similar results were observed in kidney folates. These data provide direct evidence that some of the folate synthesized by the microflora in the rat large intestine is incorporated into the tissue folate of the host. PMID- 1941262 TI - Thiamin requirement of juvenile shrimp (Penaeus monodon). AB - In a 9-wk feeding trial, juvenile shrimp (Penaeus monodon) were fed semipurified diets containing seven levels (0, 20, 40, 60, 80, 160 and 320 mg/kg diet) of supplemental thiamin hydrochloride. The dietary thiamin level required for optimal growth in P. monodon was found to be approximately 14 mg/kg diet based on hemolymph (blood) thiamin analysis. The minimum dietary thiamin level that produced substantial shrimp growth was approximately 13 mg/kg diet. Shrimp fed unsupplemented diets (thiamin content of 0.12 mg/kg diet) did not demonstrate specific deficiency signs, except those universal signs such as retarded growth, poor food conversion and low survival rates. PMID- 1941261 TI - Glutathione blood levels and other oxidant defense indices in men fed diets low in vitamin C. AB - Because ascorbic acid is an important contributor to the oxidant defense system in body tissues, we studied the effects of a low dietary intake of ascorbic acid on various indicators of oxidant defense and oxidant damage. During a 13-wk study eight healthy men (25-43 y), residing in a live-in metabolic unit, were fed controlled diets containing different amounts of ascorbic acid for four consecutive periods: period 1 = 250 mg/d for 4 d; period 2 = 5 mg/d for 32 d; period 3 = 10 or 20 mg/d for 28 d and period 4 = 60 or 250 mg/d for 28 d. Measurements were made at several time intervals of the activities of glutathione peroxidase and superoxide dismutase in RBC, DNA strand breaks in mononuclear leucocytes, glutathione concentrations in plasma and RBC and NAD and NADP in RBC. After 60 d of low ascorbic acid intakes and associated with plasma ascorbic acid levels less than 6 mumol/L, the total glutathione concentration and the reduced glutathione:oxidized glutathione ratio were decreased in plasma. At the same time NAD and NADP levels in RBC were elevated. It seems that chronic marginal vitamin C deficiency states may be associated with selected biochemical changes in oxidant defense indices. PMID- 1941263 TI - Age-related changes in whole-body amino acid kinetics and protein turnover in rats. AB - We studied whole-body amino acid kinetics in rats of approximately 70, 160, 315 and 586 g body weight. The animals were infused simultaneously with L-[U 14C]lysine, L-[1-14C]leucine, L-[U-14C]tyrosine, L-[U-14C]threonine and L-[U 14C]histidine. The plasma flux of each amino acid was estimated from its plasma specific radioactivity at the end of the infusion. Indirect estimates of whole body protein turnover were calculated, based on the plasma flux of each amino acid. Body protein synthesis was determined from the ratio of the specific radioactivities of the protein-bound and free lysine in tissue homogenate (direct method). Amino acid oxidation was calculated from the difference between the alimentary intake of each amino acid and the amount of each retained in protein. Whatever the amino acid, the plasma flux decreased progressively during growth. Positive correlations were obtained between the plasma flux of the various amino acids. The difference in indirect estimates of whole-body protein turnover obtained with different amino acids was relatively small and did not exceed 40%. At each age, the plasma flux of the various amino acids was related to their content in whole-body protein. The alimentary intake accounted for 25 to 40% of the flux for all amino acids except tyrosine (16 to 28%). The amount of each amino acid that was oxidized generally accounted for 17% of the flux.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941264 TI - Fructose and sucrose feeding during pregnancy and lactation in rats changes maternal and pup fuel metabolism. AB - We examined the effects of feeding a fructose, sucrose or reference diet during gestation and lactation on blood substrate levels and insulin sensitivity in rat adipose tissue. Female rats were fed either 50% fructose or 50% sucrose purified diets or a nonpurified diet ad libitum during gestation and lactation. Fasting blood samples were taken on d 10 of gestation and one oral glucose tolerance test was conducted on d 19 of gestation, with a second test performed on the day of weaning. All dams were killed 2 d after weaning. During gestation, fructose feeding induced hyperglycemia and hypertriglyceridemia in early pregnancy (d 10) relative to sucrose-fed rats, and hypotriglyceridemia in late pregnancy (d 19) as compared with the group fed the reference diet. Compared with the reference group, sucrose feeding also caused hypotriglyceridemia during late pregnancy. Pups delivered to fructose-fed dams were hyperglycemic at birth. In comparison with the reference group, fructose-fed dams were hypoglycemic, whereas sucrose fed dams were hypertriglyceridemic at weaning. There was no difference in each of the two oral glucose tolerance test responses between the three groups after adjusting for the baseline difference in glucose levels. However, lipid synthesis in isolated fat cells in response to insulin stimulation was significantly lower in fructose-fed and sucrose-fed rats relative to the reference group. PMID- 1941265 TI - Assessment of thermal status of somatotropin-injected lactating Holstein cows maintained under controlled-laboratory thermoneutral, hot and cold environments. AB - Two experiments, with a single-reversal design and 12 cows per experiment, were conducted to study the effects of somatotropin on thermal status of lactating cows under laboratory thermoneutral (18 to 22 degrees C, 30-50% relative humidity), hot (24-35 degrees C, 30-50% relative humidity) and cold (-5 (-) +5 degrees C, 50-55% relative humidity) conditions. Throughout the experiment six cows were injected with somatotropin (25 mg/d) and six with sodium bicarbonate. All injections were started the first day of the 30-d natural environmental period (22-35 degrees C and 41-97% relative humidity for summer experiment, and 5 (-) +5 degrees C and 4-25% relative humidity for winter experiment) before the cows were exposed alternatively to laboratory thermoneutral and hot or cold environments. The somatotropin-treated cows had higher energy intake (13 and 17%), heat production (19 and 25%), heat loss (36 and 24%) and milk energy (40 and 49%), than control cows under thermoneutral and hot conditions, respectively. The somatotropin-treated cows had higher heat production (18 and 10%), respiratory heat loss (27 and 17%) and milk energy (14 and 25%) than control cows under thermoneutral and cold conditions, respectively. The increased heat production associated with somatotropin was accompanied by increased heat losses. Part of the increased heat production was attributed to the increased milk energy and energy intake. These results suggest that increased heat production during somatotropin treatment was within the range that could be dissipated by the cows. PMID- 1941266 TI - Abomasal casein infusion and exogenous somatotropin enhance nitrogen utilization by growing lambs. AB - Growing Dorset wether lambs (23 kg initial body weight) were used to determine whether the magnitude of nitrogen retention response to daily administration of exogenous somatotropin is limited by post-ruminal amino acid availability in growing ruminants. Eight lambs surgically fitted with abomasal cannulae were fed a total mixed ration of 85% of ad libitum intake. All lambs received a continuous abomasal infusion of 2 L of water or casein and twice daily subcutaneous injections of 0 or 100 micrograms recombinant bovine somatotropin (rbST)/kg body wt for 15 d per treatment in a 2 x 2 single reversal design. The casein solution was infused at a rate (4 to 5 g nitrogen/d) to achieve 25% of nitrogen intake observed with ad libitum feeding prior to initiation of treatments. Each lamb received all four treatments. Nitrogen balance was determined on d 8 to 14 of each treatment. Casein infusion increased nitrogen balance 43.4% (P less than 0.001), and rbST increased nitrogen balance 33.5% (P less than 0.001), without significant interaction (P less than 0.88). Combined effects of casein and rbST were additive, resulting in an 89% increase in nitrogen balance when compared with water plus excipient treatment. Results suggest that the quantity or composition of absorbed amino acids, or both, limit nitrogen retention by growing lambs, and that rbST increases the efficiency of utilization of absorbed amino acids for protein deposition. PMID- 1941267 TI - Sodium pivalate treatment reduces tissue carnitines and enhances ketosis in rats. AB - Sodium pivalate, a compound conjugated to carnitine and excreted in the urine was used to induce a secondary carnitine deficiency. In the first series of experiments, rats received in their drinking water either 20 mmol/L sodium pivalate (experimental) or 20 mmol/L sodium bicarbonate (control) for 4 d, 2 wk, or 8 wk. Tissues and urine were collected, and carnitine concentrations in liver, skeletal muscle, heart, plasma and urine were determined. The total carnitine concentrations in tissues and plasma of pivalate-treated rats were significantly depressed (P less than 0.05) at all time points, except at 4 d for skeletal muscle and at 4 d and 2 wk for liver. The acylcarnitine:free carnitine ratios in urine and plasma of the pivalate-treated animals were significantly higher at all time points relative to the controls. In the second experiment, rats received either the pivalate or the bicarbonate treatments for 15 d followed by a 2-d fast. After fasting, the plasma beta-hydroxybutyrate of pivalate-treated rats was significantly higher relative to controls, but there was no significant difference in plasma glucose concentrations. The reduced plasma and tissue carnitine concentrations, increased acylcarnitine:free carnitine ratio in plasma and urine, and fasting ketosis found in pivalate-treated rats are findings also reported for human secondary carnitine deficiency due to organic acidurias. PMID- 1941268 TI - Supplementation of humans with vitamin E. PMID- 1941269 TI - Contrasting enrollment trends for BSN students in the United States and in New York State: an assessment and analysis. AB - The paper provides a description, assessment, and analysis of enrollment trends for generic and registered nurse students in baccalaureate programs in both the United States and New York state over the past 30 years. The analysis focuses on the reasons for the recent declining enrollment of both types of BSN students in New York state. Primary data sources were the National League for Nursing's annual student census statistics, policy statements and reports of the NLN and the American Nurses Association (ANA), and statements on the recruitment and retention of nurses. PMID- 1941270 TI - Research on nursing curricula content. PMID- 1941271 TI - Needs of nurse educators & clinical nurses regarding quality assurance education. AB - A study was done to determine the needs and educational interest regarding quality assurance of nurses practicing in both academic and clinical settings in Western New York. A written survey questionnaire was developed and distributed to a convenience sample. Responses were received from 98 nurse educators (47% of those contacted) and from 148 clinical area nurses (42% of those contacted). Concepts about quality assurance were itemized and respondents indicated their level of interest in obtaining further information to increase their QA competencies about each. The topics of interest to both groups were similar and included standards of care, legal issues, documentation, techniques for implementation of QA in clinical practice, and measures of quality of care. Characteristics about a continuing education offering that would be desirable were specified. PMID- 1941272 TI - Inclusion of alcoholism and drug abuse content in curricula of varied health care professions. AB - Alcoholism and drug abuse are prevalent health problems in the United States. Practitioners in nursing, medicine, and dentistry need to be cognizant of the insidious signs of chemical dependency. A descriptive survey using a researcher designed questionnaire yielded a sample which consisted of 11 medical schools, 2 dental schools, 25 baccalaureate and higher degree nursing programs, and 38 associate degree nursing programs. The survey findings indicated that the curricula for nursing, medicine, and dentistry were inadequate in chemical dependency content. This survey evidenced the need for a stronger educational effort addressing both knowledge of alcoholism/drug abuse and impaired professional practice in the curricula of the health professional programs examined. PMID- 1941273 TI - Women and AIDS: the evolution of an epidemic. AB - AIDS has only recently been recognized as a disease of women. The impact of this epidemic among the female population goes far beyond studies of contagion and prognosis. The ANA's response to the AIDS epidemic, Personal Heroism, Professional Activism: Nursing and the Battle Against AIDS (Bennett, Champlain, Grimaldi, 1988), has been to marshal the forces of nurses as caregivers, advocates, educators, and policymakers. This manuscript examines the evolution of the AIDS epidemic and its impact on women in our society. Statistics from the greater New York City area and New York state are used as a predictive microcosm for epidemiological trends in the contiguous US. Some thought is given to further evolution of the disease given present treatment modalities. Following the commitment to excellence first noted by the ANA, nursing's response to emerging trends in the epidemiology of AIDS is examined. PMID- 1941274 TI - Women's health care issues. PMID- 1941275 TI - Participatory decision making: issues and guidelines. AB - The concept of shared responsibility in decision making through the use of participatory decision making has received considerable support in nursing education. There are important omissions in the discussions and applications of this concept. Problems in the use of participatory decision making as related to information transmission; conflict, consensus, and coalitions; and faculty/administrator role differences are analyzed. Criteria and guidelines for the appropriate use of participatory decision making are provided. PMID- 1941276 TI - The relationship of predominant behavioral state and salivary cortisol in the human neonate. AB - The relationship of predominant behavioral state to levels of salivary cortisol in the newborn infant was examined. A sample of 99 healthy newborns were dichotomized into groups representing characteristic predominant state following multiple observations of state behavior. Group A (state predominance sleep) babies had a mean salivary cortisol level of 1.18 micrograms per deciliter (micrograms/dl) and Group B (state predominance awake) babies had a mean salivary cortisol level of 0.83 micrograms/dl. Analysis of variance revealed a statistically significant difference in cortisol levels between the predominance of state groups; however, the direction of the difference did not conform to the expected pattern. The role of state predominance in infant research and the unexpected directions of the cortisol levels are explored. Obtaining small samples of saliva for the measurement of cortisol was demonstrated to be an easy and unobtrusive means of studying adrenal response. Categorization of infants into state predominance groups promises to provide continued research direction as it evolves into a clinically useful tool for nursing practice. PMID- 1941277 TI - Tracking back injuries. PMID- 1941278 TI - Working hours of medical residents and housestaff. PMID- 1941279 TI - A ranking of occupations based on the blood pressures of incumbents in the National Health and Nutrition Examination Survey I. AB - Data were drawn from a subsample of the National Health and Nutrition Examination Survey I, 1971 to 1975, consisting of persons 25 years of age and older who stated they were employed in one of roughly 400 US Census three-digit occupations (n = 8130). Occupations with fewer than five persons were excluded from the analysis. Diastolic and systolic blood pressures were calculated for each of 244 occupations, simultaneously adjusting for age, gender, and body mass in an analysis of covariance model. A disproportionately high number of craft, operative, laboring, and farming jobs have incumbents with higher than average blood pressures, and a disproportionately low number of professional, managerial, and clerical jobs have incumbents with higher than average blood pressures. Jobs whose incumbents have especially high blood pressures include bartenders and dry cleaning operatives. Whether jobs cause high blood pressure or persons with high blood pressure choose those particular jobs remains unknown. PMID- 1941280 TI - Employee assistance program compliance: impact of contrasting insurance coverage. AB - Employee assistance programs are offered by employers to assist employees with personal problems through professional evaluation of the problem and referral to an appropriate treatment source. Although some research has been conducted to document the effect of these programs on such variables as absenteeism and disciplinary action, little information is available regarding compliance with clinical recommendations, ie, initiating and remaining in prescribed treatment. The present study evaluated the effect of two different rates of insurance coverage for outpatient mental health services offered by two comparable blue collar organizations. Employees from the organization with a higher rate of payment were significantly more likely to initiate treatment and to remain in treatment longer. This outcome was not accounted for by demographic differences between the groups or by differences in diagnostic categories or treatment approaches. Implications of this finding are discussed as well as the utility of an employee assistance program to prepare employees for treatment. PMID- 1941281 TI - Work-site health promotion: an economic model. AB - Despite a burgeoning interest in and acceptance of corporate health promotion, the overall economic effects of these programs are not clear. Although ultimate resolution of this question awaits detailed empiric research, a theoretical approach can be useful in structuring the problem and understanding the critical issues. The financial model presented views the firm as a value-maximizing enterprise and evaluates health promotion as a use of corporate assets. The model projects the benefits and costs to the firm of a 7-year health promotion program under a variety of assumptions regarding the employee mix and the effects of the health promotion program on health and productivity. The analysis reveals that the base case assumptions result in a program that creates value for the firm when the cost is less than $193 per participating employee per year. Firms with a highly productive, difficult to replace, and older employee group are most likely to find health promotion to be a good investment. Productivity gains produce the majority of the economic benefits of the program. Effects on health care expense alone are projected to be relatively small. Gains from reduction in employee mortality or retiree health expense are found to be insignificant in this model. PMID- 1941282 TI - Universal precautions and mortuary practitioners: influence on practices and risk of occupationally acquired infection. AB - Embalming, the most common funeral practice in the United States, may expose the embalmer to infectious diseases and blood. We surveyed the 860 members of the National Selected Morticians in 1988 to estimate the incidence of self-reported occupational contact with blood and infectious disease, assess morticians' knowledge of acquired immunodeficiency syndrome (AIDS), determine their adherence to universal precautions, and identify predictors of practices designed to reduce risk of occupational exposure to infections. Of 539 (63%) respondents, 212 (39%) reported needle-stick injuries in the past 12 months, and 15 (3%) reported percutaneous exposures to the blood of a decedent with AIDS. Those rating the risk of occupationally acquired human immunodeficiency virus infection as very high or high (194/539 [36%]) were more likely to decline funerals of decedents with antemortem diagnosis of AIDS (59/194 [30%]) and/or to charge more for such funerals (133/194 [69%]) than those who rated the risk as low to moderate (31/345 [9%], 174/135 [51%]). PMID- 1941283 TI - Industrial noise exposure and ambulatory blood pressure and heart rate. AB - Studies on the effects of long-term exposure to industrial noise on resting blood pressure have yielded inconsistent results. Ambulatory blood pressure and heart rate were monitored simultaneously with noise exposure in normotensive male industrial workers in Israel (85 aged 25 to 44 and 77 aged 45 to 65 years). In the younger group, average ambulatory systolic blood pressure was 3.2 mm Hg higher and diastolic blood pressure 2.3 mm Hg higher in subjects exposed to more than 85 dBa (P less than .001), after adjusting for potential confounding variables. In those aged 45 to 65, ambulatory systolic blood pressure was 3.3 mm Hg lower and diastolic blood pressure unchanged in noise-exposed subjects. Ambulatory heart rate was 2.7 and 2.6 beats per minute higher at the higher noise level (P = .002) in the respective age groups. These findings suggest that industrial noise exposure is associated with higher ambulatory blood pressure and heart rates in men under 45 years old, but the effect on blood pressure appears to diminish considerably with age. PMID- 1941284 TI - Effect of a total work-site smoking ban on employee smoking and attitudes. AB - A "smoke-free" policy was adopted at the Duke University Medical Center but not at the adjacent University Campus. Three months after the smoking prohibition went into effect, a cross-sectional telephone survey was conducted, using randomly selected groups of 400 employees from each campus. Subjects were queried about current and previous smoking histories and their opinion of the smoking ban. As determined retrospectively from this survey, at the time of the announcement of the policy and 6 months before implementation, 23.6% of employees at the Medical Center were smokers, compared with 20.3% on the University Campus. Three months after implementation of the Medical Center smoking prohibition, smoking cessation rates were 12.6% at the Medical Center and 6.9% on the University Campus dating back 9 months to the time of policy announcement (P less than 0.10). Mean cigarette consumption during work hours declined over this same period from 8.1 +/- 6.8 (mean +/- SD) to 4.3 +/- 4.4 at the Medical Center but showed little change on the University Campus (9.3 +/- 7.5 v 8.7 +/- 8.0). Overall, 75.8% of subjects at the Medical Center "somewhat" or "strongly" agreed with the policy compared with 73.2% on the University Campus. A follow-up survey of the cohort of current or recent ex-smokers identified on the initial survey was conducted 6 months later. This survey revealed a smoking cessation rate of 22.5% at the Medical Center and 6.9% on the University Campus, dating back 15 months to the time of policy announcement (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941285 TI - Health and illness behavior of Type A persons. AB - The complex and controversial relationship of type A behavior to myocardial infarction and other illnesses may be mediated through health habits and illness behavior. We hypothesized that type A persons tend to reject the sick role, delay in seeking medical care, seek convenient medical care facilities, are impatient for recovery, return to work before they have fully recovered, and are less likely to engage in positive health habits. A cross-sectional survey was conducted at a large corporation in Cleveland, Ohio. A detailed questionnaire that examined health-promoting and illness behaviors was sent to 385 managers, 54% of whom responded. Models tested using path analysis supported the hypotheses that type A persons are more likely than are type B employees to reject the sick role, delay in seeking medical care, be impatient for recovery, and return to work before a full recovery. The study findings imply that type A employees may be less likely to miss work for minor illnesses, but they may be prone to adverse outcomes from illnesses that require early care or assumption of the sick role. The hypothesis that type A persons are less likely to engage in positive health habits behavior was not supported. PMID- 1941287 TI - Lung cancer in metal workers. PMID- 1941286 TI - A cohort study among workers at a metal components manufacturing facility. AB - To follow-up on a proportional mortality study that showed significantly elevated proportional mortality ratios for lung cancer and a subgroup of nonmalignant respiratory diseases, we conducted a cohort mortality study (1950-1987) among 4627 employees of a metal components manufacturing facility. The findings of this study showed lower than expected mortality from all causes of death and all cancers. However, lung cancer mortality was significantly elevated (standardized mortality ratio = 131, 95% confidence interval (102-165), owing to elevated mortality among hourly workers (standardized mortality ratio = 153, 95% confidence interval 118-195). Hourly workers also showed a significantly elevated rate for the residual category "other nonmalignant respiratory disease" (standardized mortality ratio = 170, 95% confidence interval 110-251) and a significant deficit of leukemia (standardized mortality ratio = 16, 95% confidence interval 0-87). Analyses by duration of employment did not show significant trends for any cause of death. Smoking information was not available, but several indirect methods were used to estimate the potential confounding effect of smoking. PMID- 1941288 TI - Industrial accident experience of one company on 8- and 12-hour shift systems. AB - The accident reports of a company were analyzed for 10 years before and after change from 8- to 12-hour shifts. Age-sex standardized ratios were calculated for each year for on- and off-the-job accidents by severity. Times of occurrence of on-the-job accidents were also examined. Overall accident rates were reduced on the 12-hour shift schedule, but statistical significance was reached only for lower accident categories. Off-the-job injuries increased on the 12-hour shift. There were significant gender differences in accident rates on 8-hour but not 12 hour shifts. A distinct circadian pattern of accident frequency was observed. We concluded that the introduction of a 12-hour shift system did not result in increased accidents. PMID- 1941289 TI - Diversity, debate, and discourse. PMID- 1941291 TI - Postpartum mothers' preferences for nighttime care of the neonate. AB - This study, conducted in response to issues raised during implementation of a dyad care delivery system, investigated preferences of postpartum mothers for nighttime care of the neonate. For dyad as well as traditional care subjects, the availability of individual care options emerged as a theme in both personal preference and preference based on available hospital accommodation. Significant differences existed between dyad and traditional care subjects on second choices for nighttime care and on environmental variables. PMID- 1941290 TI - Second-trimester termination of pregnancy: nursing care. AB - Termination of pregnancy because of fetal abnormalities is a physically and emotionally painful event. Prostaglandin E2 (PGE2) intravaginal suppositories are an effective method for inducing labor. Patient care and pain management require both knowledge and sensitivity on the part of the nurse. PMID- 1941292 TI - Early parental touch and preterm infants. AB - Thirty-six parents were videotaped during visits with their preterm infants in a neonatal intensive care unit in order to describe some characteristics of parental touch. Parents most often touched infants' hands, backs, and heads, using stroke, hold, or contact actions of moderate intensity. Mothers and grandmothers provided more touch than fathers, and parents provided less touch to infants at or below a gestational age of 28 weeks. The results can be used as a basis for more controlled experimental studies evaluating preterm infants' physiologic responses to early parental touch. PMID- 1941293 TI - Maternal identity and early mothering behavior in previously infertile and never infertile women. AB - The differences in maternal identity and early mothering behavior were compared in previously infertile and never infertile women in this pilot study to evaluate the relationship between previous infertility and the early maternal experience. Women were tested by questionnaire, observation, and interview. No significant differences were noted between groups for quantitative early mothering behavioral measurements. Previously infertile mothers demonstrated lower postpartum maternal identity scores, delay in preparation of the home environment, and less self confidence. PMID- 1941294 TI - Clomiphene-induced mood swings. AB - A study of couples' perceptions of infertility treatment with clomiphene (clomiphene citrate) revealed mood swings in 9 out of 14 women using the drug. This paper describes the mood swings and the responses of women and their spouses. Three phases of mood swing response emerged from the data: lacking awareness of the relation of the mood swings to the drug; gaining awareness of that relation; and managing the mood swings. The results of the study provide important information for nurses counseling couples who are experiencing clomiphene-induced mood swings. PMID- 1941295 TI - Marketing the nursing practice of obstetrics. AB - This article offers nurses a conceptual framework for marketing their skills and discusses how that framework can be applied to obstetric nursing practice. A thorough understanding of the framework presented will provide maternity nurses with the foundation they need to participate effectively in a marketing plan. Examples of the application of the framework to specific clinical situations are examined. PMID- 1941296 TI - Slow and fast pathways in the human rod visual system: electrophysiology and psychophysics. AB - Under most conditions, increasing the intensity of a flickering light makes the flicker more conspicuous. For a light flickering at 15 times per second, however, increasing the intensity can cause the flicker to disappear before reappearing again at higher intensities [Vision Res. 29, 1539 (1989)]. This flicker disappearance or null is also evident in human electrophysiological recordings at the same intensity levels. These results point to a duality within the rod visual pathway, in which flicker signals travel through a slow and a fast pathway and then recombine at a later stage. At 15 Hz the slow rod flicker signals are delayed by half a cycle relative to the fast signals. Thus, when the two signals are recombined, they destructively interfere and diminish the perception of flicker. The dual-pathway interpretation is supported by both electroretinographic and psychophysical evidence showing a phase difference of half a cycle between 15-Hz rod signals just below and just above the null region. These effects are apparent not only in the normal observer but also in an achromat observer who lacks functioning cone vision. PMID- 1941297 TI - Spatial linearity of the pattern electroretinogram. AB - We modeled the spatial-frequency sensitivity of the human pattern-reversal electroretinogram (PERG) with the linear, two-parameter, spatially bandpass model of Kelly [J. Opt. Soc. Am. A 2, 810 (1985)]. In the model temporal linearity or linearity with luminance is not assumed, but linearity with contrast is assumed. Measurements relating PERG amplitudes to stimulus element size were taken from 13 earlier reports. Stimuli were two-dimensional Fourier analyzed. The bandpass model fitted well and thus supported linearity (spatial superposition) and suggested that large PERG's to large checks (low-pass data) reflect mainly responses to higher-spatial-frequency stimulus components. PMID- 1941298 TI - Simple expressions for scattering by a chiral elliptic cylinder of small cross sectional dimensions. AB - An integral-equation method is used to derive simple expressions for the field scattered by infinitely long chiral cylinders of elliptic cross sections; the derived expressions are applicable when the cross-sectional dimensions are electrically small. Reductions for the scattering of plane waves are obtained. The derived results can be extended to thin strips. PMID- 1941299 TI - Reversed rotary motion perception. AB - A stroboscopically presented revolving annulus composed of dots is used to elicit rotary motion perception. Observers judge the direction of rotary motion. We find sharp and gradual transitions in the probability for reversed motion perception as a function of the angle of rotation between successive frames. These transitions reveal that matches between nonsuccessive frames can dominate motion perception. The transitions are scale invariant. The strength of a match is discussed in terms of a motion strength function, which is a separable function of the angle of rotation between successive frames and the frame repetition rate. The dependence of motion strength on the frame repetition rate (time function) is computed from the transitions. The similarity of this time function for rotary motion with the time function for linear motion [Psychol. Rev. 88, 171 (1981)] suggests that mechanisms for the discrimination of rotary motion address local detectors of linear motion. PMID- 1941301 TI - Involuntary insurance. PMID- 1941300 TI - Enterococcus: an old pathogen with new tricks. AB - Recent clinical enterococcal isolates from the Oklahoma City Department of Veterans Affairs Medical Center were screened for high-level aminoglycoside resistance, vancomycin resistance, beta-lactamase production, and hemolysin production. Twenty-nine of 53 (55%) enterococcal isolates had high-level resistance to gentamicin, kanamycin, or streptomycin; 27 of these isolates were from the blood and 16 (59%) showed high-level gentamicin resistance. Twenty-one percent of 259 enterococcal isolates from blood, urine, stool, and other sources were hemolytic. Of thirteen blood isolates tested for both high-level gentamicin resistance and hemolysin production, 6 (46%) showed both characteristics. Vancomycin-resistant or beta-lactamase-producing isolates were not found. Nineteen of 21 charts from patients with premortem enterococcal blood isolates were reviewed, and no correlation was found between appropriate antibiotic treatment for high-level gentamicin-resistant or susceptible enterococcal bacteremia and outcome. Enterococci with multiple high-level aminoglycoside resistance, but not vancomycin resistance or beta-lactamase production, are common at this referral medical center. Clinical microbiology laboratories in Oklahoma should routinely screen enterococcal isolates causing potentially serious infections (eg, from blood or cerebral spinal fluid) for high-level aminoglycoside resistance. PMID- 1941302 TI - Health screening in elderly Oklahomans. AB - A total of 550 males and 457 females in their 60s and 70s were screened for height and weight, blood pressure, glucose, cholesterol, and hemoglobin. Statistical analysis was performed using SAS software. Male values were abnormal for all screening parameters except for cholesterol. Statistically significant lower hemoglobin in males suggests that blood loss may be a problem, and in males increases in body weight and glucose may herald a higher frequency of cardiovascular disease. Control of blood pressure, weight reduction, decreased consumption of fat and salt, and regular exercise may be the health imperatives in this group of elderly Oklahomans. PMID- 1941303 TI - Interview with Senator Don Nickles on domestic health care issues. Interview by Richard L. Reece. AB - Senator Nickles (R-Okla) was interviewed in March in his Oklahoma City office on the 18th floor of the Liberty Bank Building. The interview was shortened by a late start and because the Senator was on his way to an editorial meeting of the Daily Oklahoman. Nonetheless, Senator Nickles, a young and energetic man in his early forties, was relaxed and in no apparent rush. Nickles, still the youngest Senator in Washington, has been a US Senator for 11 years. Because of the combination of youth and promise of long tenure, he is considered to be a rising power in the Senate. He is a conservative and a philosophical ally of medicine. PMID- 1941304 TI - A case for capital punishment. PMID- 1941305 TI - Long-term effects of tibial angular malunion on the knee and ankle joints. AB - Twenty-seven patients with 28 tibial fractures were evaluated for an average of 8.2 years (range 6.0-12.3 years) following their injuries. There were 16 closed and 12 open fractures, all of which healed uneventfully. Overall, 50% of the ankles and 75% of the knees were rated good to excellent. The patients' knee and ankle joint malalignments were extrapolated using a method previously published. This was made possible by knowing both the degree and site of angular deformity. Correlation between joint malalignments and clinical outcome were performed. Analysis showed that greater degrees of ankle malalignment produce poorer clinical results (p = 0.001). Conversely, the patients with lesser degrees of ankle joint malalignment had a higher percentage of good to excellent results (p = 0.006, p = 0.003, p = 0.03). The knee results did not correlate with the degree of joint malalignment (p = 0.82). The findings in this study show that there is merit in reducing tibial fractures as close to anatomical configuration as possible to lessen the chance of early degenerative arthritis. PMID- 1941306 TI - Percutaneous and limited open reduction of the articular surface of the distal radius. AB - Between 1979 and 1986, 40 patients with intraarticular fractures of the distal radius, in which anatomic reduction could not be obtained by closed manipulation or external fixation, underwent a combination of percutaneous and/or limited open reduction techniques to restore articular congruity. All 40 patients' radiographs that were retrospectively reviewed with an average follow-up of 4 years showed satisfactory extraarticular alignment in 85% of cases, and 37 patients (92.5%) demonstrated an articular step-off of less than or equal to 1 mm. Thirty-one patients retrieved for follow-up had a good functional result. The treatment goals of intraarticular fractures of the distal radius are anatomic restoration of the joint surface and optimal fixation to maintain reduction in an effort to prevent posttraumatic arthrosis of the wrist. PMID- 1941307 TI - Ligamentotaxis for comminuted distal radial fractures modified by primary cancellous grafting and functional bracing: long-term results. AB - Ligamentotaxis with the use of external fixator offers a sound method for treating comminuted distal radial fractures. In an effort to shorten the period of external fixation, primary cancellous bone grafting and functional bracing were used as an adjunct to ligamentotaxis. The external fixator was left in place for 3 weeks, followed by functional bracing for another 3 weeks. This paper presents the results of 54 patients with an average follow-up of 31.5 months. Results showed that 80% of the patients regained full range of motion in their hands, wrists, and forearms. More than 80% of the patients regained strong and pain-free wrist functions. Radiologically, there was no loss of reduction or shortening. Nine percent of patients suffered mild arthritic changes in the radiocarpal joints. Final assessment showed that 90% of patients had excellent or good results. Late complications were minimal, apart from the problems of the distal radio-ulnar joints. PMID- 1941308 TI - Immediate internal fixation of high-energy open forearm fractures. AB - Eighteen patients with Gustilo and Anderson Grade III A (7), III B (8) or III C (3) open diaphyseal forearm fractures were treated with a protocol consisting of extensive primary debridement, immediate open reduction, dynamic compression plate fixation, and vascular repair when indicated. This was followed by routine redebridement at 24 to 48-h intervals until wound status allowed completion of soft tissue reconstruction. Bone grafting was performed at 8 to 10 weeks following obtainment of a closed soft tissue envelope for injuries with extensive comminution or bone loss (5 patients, 7 fractures). Subsequent procedures such as tendon transfers, scar revision, joint arthrodesis, or secondary nerve reconstruction were required in 8 of 18 patients. Minor complications related to delayed wound healing occurred in 3 individuals (15%). One deep infection of a fractured radius occurred in a patient with a floating elbow and failed free flap. Salvage with debridement, retention of hardware, and a second free flap resulted in fracture union. One patient required a second bone graft to obtain union of a segmental forearm defect. Amputation was performed in one patient following failed forearm replantation with greater than 8 h warm ischemia time. Immediate debridement and plate fixation of Grade III forearm fractures performed in conjunction with aggressive soft tissue management provided good or excellent results in 12 patients (66%) and is an acceptable treatment alternative in these difficult injuries. PMID- 1941309 TI - Internal fixation with a self-compressing plate and lag screw: improvements of the plate hole and screw design. 1. Mechanical investigation. AB - For a number of years, self-compressing plates, with oval holes and using special drill guides, have been in use. Recently, the advantages offered by lag screw interfragmentary compression inserted through the plate have gained prominence. Often such screws are inserted in an inclined position toward the fracture plane for better efficiency. It has also become evident that inclined screws placed into oval holes undergo a displacement toward the fracture. Efforts to improve the effect of this technique have led to a new plate and screw interaction that is described herein. The result is versatility and efficiency of the fracture fixation. PMID- 1941310 TI - Internal fixation with a self-compressing plate and lag screw: improvements of the plate hole and screw design. 2. In vivo investigations. AB - A mechanically improved design of bone plate and screw was compared in vivo with conventional plate fixation. This method was investigated biologically in a standardized osteotomy model on sheep tibiae. It was found that maintenance of reduction of an osteotomy was facilitated and there was no adverse effect of this fracture fixation system on bone remodeling. The modified implant permits the reduced surgical approach to the bone through one plane and optimal fixation of the fracture or osteotomy. PMID- 1941311 TI - Surgical treatment of fractures of the capitellum in adults: a modified technique. AB - Five adults with fractures of the capitellum (Hahn-Steinthal type) were treated by a modified improved technique of open reduction and internal fixation in 1988 and 1989. Full range of motion was achieved in all cases at 4 months. PMID- 1941312 TI - Supraintercondylar fractures of the distal humerus: results of internal fixation. AB - Operative treatment is considered to be the primary method of treatment for supraintercondylar fractures of the distal end of the humerus. Anatomical reduction and stable fixation of the fracture allows for early postoperative functional treatment and, subsequently, better results than other methods. Two series of patients with supraintercondylar fractures of the humerus, one from 1969 to 1980, and the second from 1981 to 1988, are presented. Although these series do not differ widely in their final outcomes, certain philosophies and operative techniques did change for the better. PMID- 1941313 TI - Occult orthopaedic trauma in the multiply injured patient. AB - A retrospective review of 111 multitrauma patients revealed that of 401 orthopaedic injuries, 24 injuries (6%) were not initially diagnosed in 20 patients. Patients with occult injuries tended to have greater overall trauma, as reflected by lower trauma and lower Glasgow coma scores and longer hospital and intensive-care unit stays. Twenty prospectively identified cases were added to the series to further define risk factors. Seventy percent of occult bony injuries were ultimately diagnosed by physical examination and plain radiographs alone. Only 27% of cases required sophisticated imaging techniques for diagnosis. Based on these 44 cases of occult injuries in multitrauma victims, the following risk factors were identified: (1) significant multisystem trauma with another more apparent orthopaedic injury within the same extremity, (2) trauma victim too unstable for full initial orthopaedic evaluation, (3) altered sensorium, (4) hastily applied emergency splint obscuring a less apparent injury, (5) poor quality or inadequate initial radiographs, and (6) inadequate significance assigned to minor signs/symptoms in a major trauma victim. Due to the nature and extent of the overall trauma, all injuries cannot be diagnosed on initial patient evaluation. PMID- 1941314 TI - Biomechanical testing of new and old fixation devices for vertical shear fractures of the pelvis. AB - Malgaigne fractures of the pelvis have been treated with many different methods of fixation. We developed a plate for use on the anterior aspect of the sacroiliac (SI) joint using information obtained from cadaveric dissections and computed tomography (CT) scans of male (50) and female (50) pelvises. We tested each of six pelvises in the Instron, with five different fixation systems. Our results showed that the weakest system was the anterior quadrilateral frame plus two symphyseal plates. When comparing three posterior screws with the SI joint plate, the difference was not statistically significant. However, in both of these systems, a second symphyseal plate added to the overall stability. PMID- 1941315 TI - Bipolar hemiarthroplasty for fracture of the femoral neck. AB - Controversy in the treatment of displaced femoral neck fractures in the elderly focuses on the use of fixation versus the use of a prosthesis. Beginning in 1980, at The New York Hospital-Cornell Medical Center, it became routine to treat elderly patients for displaced fractures with bipolar hemiarthroplasty. This retrospective study evaluates the morbidity, mortality, and clinical and social functioning of 246 consecutive patients treated with bipolar hemiarthroplasty for Garden III and Garden IV nonpathological fractures. Follow-up ranged from 1 to 6 years. Of the 246 patients with 247 femoral neck fractures, 201 were female and 45 were male; the average age was 78 years. Fourteen patients (5.7%) died during the postoperative hospitalization. Thirty-one patients (13.3%) died within the first year following surgery. Mortality was related to the number of preexisting medical conditions: patients with four or more preexisting conditions had a significantly higher mortality than others (p less than 0.001: chi 2). The overall wound infection rate was 3.2%. There were only two failures (0.9%), both for deep infection, requiring Girdlestone debridement. One patient was revised for infection with successful reimplantation. There were two postoperative dislocations (0.9%), both reduced closed. Only one bipolar (0.4%) required conversion to a total hip replacement for a fractured acetabulum, none for arthritic wear. No radiographic evidence of significant acetabular erosion or protrusion nor femoral component loosening was noted. Clinical results were evaluated using the Hospital for Special Surgery Hip Rating Scale.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941316 TI - Fatigue failure of the sliding screw in hip fracture fixation: a report of three cases. AB - Hardware failure of the sliding screw system used in hip fracture fixation is rare. The fatigue failure of the sliding screw is always related clinically to nonunion or refracture along the path of the screw. In both situations, cyclic loading of the implant exceeds its endurance limit, and failure can ensue. Three cases of failure of the sliding screw are presented: a nonunion of a basicervical fracture, a nonunion secondary to stress fracture at the plate-barrel junction, and a refracture through the femoral neck after healing of an intertrochanteric fracture. A biomechanical analysis of the stresses on the sliding screw focuses on design features such as the internal threaded region used for the compression screw or the barrel length that creates increased stresses in the screw, thus lowering the number of cycles to failure. Based on this analysis, recommendations are made concerning implant design and surgical technique. PMID- 1941317 TI - Mechanical characterization of femoral interlocking intramedullary nailing systems. AB - The most important mechanical characteristics of a nailing system are related to its stiffness (rigidity) and strength. This study evaluates the properties of three commercially available interlocking intramedullary nail systems using standardized test methods. An understanding of the mechanical properties along with the clinical data will assist the surgeon in choosing the optimum implant. Testing indicates that the bending strength and stiffness of the Grosse & Kempf, the AO/ASIF Universal, and the Russell-Taylor interlocking intramedullary nail designs are comparable. It is therefore not surprising that all of these nail systems have excellent clinical results. However, the nonslotted design is approximately 30 times more resistant to torsional loading than either the partially slotted design of the Grosse & Kempf nail or the fully slotted design of the AO/ASIF nail. The clinical relevance of the torsional values may not be known until a long-term comparison of the complication rates for these different systems is available. Analysis of screw design reveals a tradeoff in bending strength when compared to amount of bone purchase. The bending strength of fully threaded screws (allowing bicortical fixation) is less than that of partially threaded screws (allowing only unicortical fixation), which shows that for the implants tested, increased bone purchase requires a compromise in strength for similar sized screws. PMID- 1941318 TI - Unilateral external fixation until healing with the dynamic axial fixator for severe open tibial fractures. AB - One hundred one cases of open tibia fractures were treated until healing with a unilateral external fixation device that permits fracture site compression with weight bearing. There were 38 type II and 63 type III (24 IIIA, 33 IIIB, six IIIC) open fractures. A standard protocol was followed including irrigation and debridement and, when necessary, flap coverage (19 cases) and bone grafting (31 cases). Fixators were applied at the first debridement and removed when the fracture was healed. All patients were permitted early partial weight bearing and progressed to full weight bearing with fixator dynamization. Ninety-six cases healed in the fixator (12-50 weeks; average, 24.6). Three of the five failures were associated with screw complications. Five patients required screw changes and 29 required oral antibiotic therapy for screw complications. Ninety-five percent of healed cases had angulation of less than 10 degrees (in any plane). There were only six fracture site infections during the course of treatment. Dynamic axial fixation may be applied at the first debridement and be used until healing in severe open tibia fractures. Change of the fixator to another treatment method is not required. PMID- 1941319 TI - Assessment of tibial fracture union by 35-45 degrees internal oblique radiographs. AB - Thirty-five to 45 degrees internal oblique radiographs were used in the assessment of tibial fracture healing. This view is particularly helpful when routine radiographic examinations (anteroposterior and lateral) are nondiagnostic in assessing tibial fracture healing. The technique was helpful in the diagnosis of four occult nonunions as well as in showing the position of a bone graft when used. The authors recommend this view when a decision about tibial fracture healing cannot be made from routine radiographs. They recommend this view before resorting to tomograms of the tibia. PMID- 1941320 TI - Healing patterns of transverse and oblique osteotomies in the canine tibia under external fixation. AB - Healing patterns were compared between transverse and 60 degrees oblique osteotomies in canine tibiae stabilized under external fixation. Under similar in vitro testing conditions (osteotomy ends in contact), the axial stiffness of the oblique osteotomy under external fixation was 45% of the paired transverse osteotomy. Under torsion and bending, the two sides exhibited similar fixation rigidity. The animals put significantly less weight on the oblique side than on the transverse side in the early phases of bone healing (p less than 0.05 for static and p = 0.024 for dynamic weight bearing). The osteotomy bending stiffness at 60 days (in vivo) and the torsional stiffness of osteotomy union measured after sacrifice at 90 days were significantly higher on the transverse side (p = 0.013 and p = 0.016, respectively). Intracortical new bone formation was significantly higher on the transverse side (p less than 0.01), indicating a difference in the rate of cortical healing and remodeling. The average pin removal torque was significantly lower on the oblique side (p less than 0.05), a sign of increased pin loosening. In the clinical situation, unstable oblique or spiral fractures should be protected from weight bearing even under stable external fixation due to the delayed recovery of bone union stiffness property as well as increased pin tract problems. PMID- 1941321 TI - Radiological evaluation of peroneal tendon pathology associated with calcaneal fractures. AB - Review of MRI, CT, and radiographic views of 21 intraarticular calcaneal fractures revealed eight cases of peroneal tendon subluxation or dislocation. Routine radiographs were nondiagnostic for the soft tissue injury in five of these eight patients. The anatomic relationships between the tendons, retinaculum, and fibular groove could typically be identified easily on MRI or CT scan. In this combined injury, recognition of the peroneal tendon subluxation or dislocation and its proper management may reduce subsequent tendon dysfunction; it may also alter the calcaneal fracture management. PMID- 1941322 TI - Nonunion of a carpal scaphoid fracture in a child. AB - We report a case of a nonunion of a carpal scaphoid in a child treated successfully by cast immobilization. Contrary to the general opinion that nonunion of the scaphoid bone should be treated operatively, even in children, we showed that healing can be obtained by nonoperative treatment methods. PMID- 1941323 TI - Monteggia type I equivalent lesion: diaphyseal ulna and proximal radius fracture with a posterior elbow dislocation in a child. AB - A rare type I equivalent Monteggia lesion in a child, diaphyseal ulna and proximal radius fracture with a posterior elbow dislocation, is described, as well as the probable mechanism of injury. An excellent result was obtained with nonoperative treatment. PMID- 1941325 TI - Dislocations of the sternoclavicular joint: anatomic basis, etiologies, and radiologic diagnosis. AB - Dislocations of the sternoclavicular joint are relatively uncommon, but diagnosis and management can be difficult, with posterior dislocations being potentially very serious. The anatomy of the joint, and the mechanisms of dislocation, are described. The radiologic diagnosis is discussed and three case reports are presented to illustrate varieties of dislocation. Although computed tomography is the ideal method of demonstrating the sternoclavicular joint, some specialized plain film projections are often useful. These should be more widely known and are described and illustrated. Treatment is briefly discussed. PMID- 1941324 TI - A calcified ligamentum teres mimicking entrapped intraarticular bony fragments in a patient with acetabular fracture. AB - A motor vehicle accident victim presented with a fractured acetabulum and had apparent entrapped bony intraarticular fragments seen on computed tomography scanning. At surgery, these fragments were found to be a partially avulsed calcified ligamentum teres that was apparently caused by a previous injury of the same hip. Excision of the calcified ligament and surgical stabilization of the acetabulum were performed. A calcified ligamentum teres may be confused with entrapped bony fragments and therefore cause difficulty in the evaluation and management of acetabular fractures. PMID- 1941326 TI - The anterosuperior insertion of the temporomandibular joint capsule and condylar mobility in joints with and without internal derangement: a double-contrast arthrotomographic investigation. AB - The insertion of the anterior temporomandibular joint capsule at the temporal bone constitutes an anatomic boundary of the joint. When condylar translation exceeds this site, the joint is classified as hypermobile. In this study, the distance from the apex of the articular eminence to the antero-superior capsule insertion was assessed in double-contrast arthrotomograms from 192 joints with and without disc displacement. Maximum condylar translation was also measured. The insertion point of the antero-superior capsule was, on the average, located 4.4 mm (SD, 1.7 mm) anterior to the apex of the eminence, regardless of disc position. Hypermobility was present in 56 joints. Sixty-eight percent of the hypermobile joints had a reducing disc and 62% of all the joints with a reducing disc were hypermobile. In joints with permanent disc displacement, the condyle generally was halted posterior to the apex of the eminence, but could pass extensively anterior to it. Condylar hypermobility thus does not exclude the presence of a permanently displaced disc. In 71% of patients with hypermobility, the condition was bilateral. Because of the close topographic relationship between the joint and nerve branches in the anterior vicinity of the joint, a hypermobile condyle may mechanically irritate the masseteric and deep posterior temporal nerve branches. PMID- 1941327 TI - Measurement standards for the prevertebral region in the lateral soft-tissue radiograph of the neck. AB - One hundred thirty-one lateral soft-tissue radiographs of the neck, taken over a 6-month period, were reviewed. Eighty-six radiographs were normal. The mean prevertebral soft-tissue thickness in the posterior-anterior dimension for each normal radiograph was measured. The mean thickness in the retropharyngeal region ranged from 6.2 mm in the infant to 3.7 mm in the adult, while the mean thickness in the retrotracheal region ranged from 9.2 mm in the preschool group to 12.1 mm in the adult. PMID- 1941328 TI - Changing trends in oral cancer in the United States, 1935 to 1985: a Connecticut study. AB - An extensive epidemiologic study was undertaken in an attempt to analyze patterns of oral cancer distribution and demography in Connecticut between 1935 and 1985. Sources of data for the investigation included both the Connecticut Tumor Registry (CTR) and the University of Connecticut Oral Pathology Biopsy Service. During the 51-year study period, 9,708 cases of primary oral cancer were reported to the CTR. Male age-adjusted incidence rates for overall oral cancer remained stable between 1935 and 1964 (14.5 to 14.8 per 100,000), with a gradual decline to 10.9 per 100,000 in the early 1980s. In contrast, age-adjusted rates for females advanced approximately threefold, from 1.4 per 100,000 in the 1930s to 4.1 per 100,000 in the early 1980s. There was a decrease in age-specific rates of oral cancer in males aged 70 and older; in contrast, age-specific incidence rates in females increased steadily over the same period. It was also found that female birth cohorts born in 1900 and later exhibited higher oral cancer incidence rates than those of previous cohorts. Between the 1960s and the present, male patients 30 to 39 years of age exhibited a nearly fourfold increase in oral cancer incidence; this was not observed among similarly aged females. Connecticut counties with highest oral cancer incidence rates in both sexes were the more densely populated Hartford and New Haven counties. In general, the picture of oral cancer, as revealed through analysis of cases accessioned by the University biopsy service between 1975 and 1986, exhibited similar trends to those disclosed by analysis of CTR data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941329 TI - Correlation between pain and synovitis in patients with internal derangement of the temporomandibular joint. AB - A correlation between pain scores by questionnaire and synovitis index via arthroscopic inspection was made in 28 patients with internal derangement of the temporomandibular joint (TMJ) with closed lock. A statistically significant but weak correlation was found between the visual analog scale of pain and the index of distribution of synovitis. However, in the questionnaire, pain on chewing had a positive correlation with both the intensity and distribution of synovitis in the TMJ. This study indicates that synovitis is one cause of TMJ pain in patients with closed lock. PMID- 1941330 TI - Temporomandibular joint arthrocentesis: a simplified treatment for severe, limited mouth opening. AB - Seventeen patients complaining of suddenly occurring, severe, and persistent limited mouth opening were treated by irrigation of the upper compartment of the affected temporomandibular joint with lactated Ringer's solution. This simple treatment was found to be highly effective in reestablishing normal opening and relieving pain for a follow-up period of 4 to 14 months. PMID- 1941331 TI - Comparative study of the treatment of mandibular fractures with vestibular and lingual wire splints. AB - One hundred forty-two patients with mandibular fractures were studied during the 3-year period of 1988 to 1990. One hundred ten patients treated with lingual arch wires comprised the study group and 32 treated with routine labia/buccal arch wires formed the control group. Bone healing was analyzed with clinical and sonic methods in both groups. It was estimated that the clinical and sonic evidence of the mandibular body fragments union appeared earlier and the infection rate was lower in the study group than in the control group. It was concluded that lingual wire splints are preferable for treating fractures of mandibular body, alveolar ridge, and in patients with deep overbite. PMID- 1941333 TI - A comparative study of the treatment of unilateral fractured and dislocated mandibular condyles in the rabbit. AB - This study evaluated the results of three methods of managing simulated unilateral dislocated fractured mandibular condyles in the rabbit. The first method consisted of surgical reduction of the fractured condyle to its anatomic position and its subsequent fixation with a titanium plate. The second method differed from the first by completely detaching the condyle, then replacing it as free graft. The third method left the fractured condyle in its dislocated position outside the glenoid fossa. Eighteen rabbits were used, 6 animals for each method. Half the animals in each group were killed at 4 weeks, the other half at 14 weeks postoperatively. Clinical, morphologic, functional, radiologic, and histologic examinations were conducted on all animals. The results indicated that open reduction with internal fixation with no disruption of the blood supply to the condyle provided the most favorable results. While closed reduction without internal fixation gave good functional results, definite reduction in ramus height on the operated site was observed in this group of animals. Animals that had open reduction and internal fixation using the condyle as a free graft did not do as well as the other two groups. Despite good mouth opening and occlusion, more animals showed facial asymmetry and it was more severe. None of the condyles were lost as result of necrosis, but healing took longer when compared with the other group of animals. PMID- 1941332 TI - Growth potential of the rat clavicle. AB - An experiment was performed to determine whether the clavicle, which is capped with secondary cartilage at both ends, is endowed with a tissue-separating quality or is only adaptive to forces exerted by the surrounding structures. The medial end of the clavicle from 10-day-old male rats was transplanted across the interparietal suture into an opening in the adjoining parietal bones corresponding to the outline of the transplant. The transverse dimensions of the neurocranium when measured at 25 and 35 days of age were greater in the animals with transplants than in the untreated controls. Histologic examination showed that although the cartilaginous component of the transplants was reduced, the zonal arrangements was comparable to that in situ. It was concluded that the medial end of the clavicle has a potential for separating skeletal components and that preservation of the basic structure is dependent on mechanical resistance. PMID- 1941334 TI - Biomechanical performance of tapercut needles for oral surgery. AB - A new tapercut needle has been designed and developed for closure of the oral mucous membrane in oral surgery. It is a sharp needle with short cutting edges that easily penetrates through a small needle puncture hole. It is manufactured from a unique stainless steel alloy that resists bending and fracture. Biomechanical performance tests and clinical experience confirm its superiority over the standard reverse cutting edge needle for use in oral surgery. PMID- 1941336 TI - Standardized surgical terminology for the excision of lesions in bone: an argument for accuracy in reporting. PMID- 1941335 TI - Assessing neck extension-flexion as a basis for temporomandibular joint dysfunction. AB - In the August 1987 issue of the Journal of Oral and Maxillofacial Surgery, Weinberg and LaPointe published an article entitled "Cervical Extension-Flexion Injury (Whiplash) and Internal Derangement of the Temporomandibular Joint" in which they proposed an explantation for injury to the temporomandibular joint resulting from certain motor vehicle accidents. In this article, the previous mechanism is assessed and the authors conclude that it is inaccurate. PMID- 1941337 TI - Amputation neuroma: a late complication following sagittal split osteotomy of the mandible. PMID- 1941338 TI - Bilateral submandibular sialolithiasis and concurrent sialadenitis: a case report. PMID- 1941339 TI - A conservative approach to the management of orofacial vascular lesions in infants and children: report of cases. PMID- 1941340 TI - Pseudoaneurysm as a complication of arthroscopy: a case report. PMID- 1941341 TI - Polycystic parotid disease: a case report. AB - A case report of a 14-year-old girl, presumed to have PPD, is presented. Those manifestations of this patient's disease that can be added to the classic picture of PPD include a decreased salivary flow rate and a sialochemistry that reflects a mild chronic parotitis. In addition, cysts and sialoliths were demonstrated grossly rather than microscopically. PMID- 1941342 TI - Infiltrating (intramuscular) benign lipoma of the head and neck. PMID- 1941344 TI - Infection associated with orbital subcutaneous emphysema. PMID- 1941343 TI - Angioedema associated with angiotensin-converting enzyme inhibitors. AB - A review of two cases of angioedema associated with therapeutic doses of the angiotensin-converting enzyme inhibitor enalapril are presented along with a review of the relevant literature. Although angioedema of the facial and oral pharyngeal regions is a relatively rare occurrence with the use of ACE inhibitors, recognition of these agents as the cause of such a condition, when subacute, can lead to a rapid cure. Knowledge of these effects may also be helpful in the management of an acute clinical manifestation and, as importantly, may help prevent a recurrent episode due to the ill-guided continuation of the drug. PMID- 1941345 TI - Central neurofibroma of the mandible: report of a case. PMID- 1941346 TI - Auxiliary devices for open reduction and fixation of displaced mandibular angle fractures. PMID- 1941347 TI - Seeing is believing. PMID- 1941348 TI - An accurate point of view? PMID- 1941349 TI - Advantages and disadvantages to hiring an associate with no contract. PMID- 1941350 TI - Evaluation of direct agglutination test (DAT) and ELISA for serodiagnosis of visceral leishmaniasis in India. AB - The direct agglutination test (DAT) and the enzyme-linked immunosorbent assay (ELISA) were used for serodiagnosis of parasitologically confirmed Indian visceral leishmaniasis (VL) cases. All the sera of VL cases were positive by both the methods. DAT titres of VL cases were greater than or equal to 1:3,200, and ELISA values were greater than or equal to 0.55 1:400 dilution. In the control group, sera of widely prevalent diseases of India, such as leprosy, tuberculosis, malaria, and liver cirrhosis, were included. Both tests could discriminate between VL and other patients of the control group. The sera of post-kala-azar dermal leishmaniasis (PKDL) patients gave OD values of greater than 0:55 and had DAT titres of 1:1,600. Both tests are sensitive and specific for the diagnosis of VL cases. DAT, being simpler and more economical, will be suitable for diagnosis and epidemiological studies for VL under rural conditions of India. PMID- 1941351 TI - Neopterin and beta 2-microglobulin and the assessment of intra-blood-brain barrier synthesis of HIV-specific and total IgG. AB - In HIV-seropositive patients, we evaluated the clinical utility of measuring combinations of serum and CSF levels of neopterin and beta 2-microglobulin (beta 2-M) (by RIA), as well as the intra-blood-brain-barrier (IBBB) IgG synthesis rate, IgG index, and HIV antibody index (by rate nephelometry, EIA, and formulae) for the assessment of HIV infection of the CNS. We studied paired sera and CSF from 31 HIV-seropositive patients: asymptomatic (16), ARC (12), and AIDS (3). A normal serum neopterin level predicts normal levels of serum beta 2-M, CSF neopterin, or CSF beta 2-M in 90%, 100%, and 100%, respectively, of our patients. An elevated serum neopterin level predicts an elevated level of serum beta 2-M or CSF neopterin in 81% and 62%, respectively, of cases. The HIV antibody index and IBBB IgG synthesis rate or IgG index must be determined separately because they do not predict each other and are not predicted by levels of neopterin or beta 2 M. PMID- 1941352 TI - Evaluation of a new western blot strip for human immunodeficiency virus. AB - With the isolation of the human immunodeficiency virus (HIV), numerous assays have been developed to detect antibodies to the retrovirus. The manufacturers' recommend that all sera exhibiting a positive enzyme immunoassay be confirmed by the more specific Western blot test (WBT). Recently, a new WBT strip was released for detection of antibodies to HIV. Four hundred patients' sera and 22 CDC proficiency samples were each tested with these strips and with a WBT strip prepared within the laboratory using the CDC techniques. The strips were then evaluated for banding pattern with the reactions recorded on a scale of 0 to 4+ for each band consistent with HIV response. Criteria for positive results were based on the ASTPHLD/CDC criteria. Primary emphasis was on antibody banding to gp41 (envelope protein) and p24 (core protein). The new strips showed appropriate changes in level of antibody, especially for declining antibody to p24. When the banding pattern for antibody to gp41 was compared to the standard strips, the new strips showed a sensitivity of 99.6% and specificity of 99.4%. The presence or absence of antibody to p24 on the new strips versus the standard strips showed a sensitivity of 93.7% and specificity of 99.5%. PMID- 1941353 TI - Bilirubin diglucuronide as the main source for in vitro formation of delta bilirubin. AB - To clarify which of the bilirubin moieties is responsible for the formation of bilirubin bonded to albumin (delta bilirubin) in icteric serum, the in vitro formation of delta bilirubin from bile acid-free bilirubin glucuronides and unconjugated bilirubin was examined by high-performance liquid chromatography. Bovine serum albumin (150 mumol/liter) was mixed with equimolar bilirubin diglucuronide (BDG), bilirubin monoglucuronide (BMG), or unconjugated bilirubin (UCB) and incubated in the dark at 37 degrees C under argon gas saturation. Although no delta bilirubin was formed immediately, formation eventually occurred and increased with time. A similar amount of delta bilirubin was formed when human serum albumin was used instead of bovine serum albumin. Of the three types of bilirubin, BDG was found to be the greatest source of delta bilirubin, whereas UCB produced the least. On the other hand, photoirradiation of a mixture of bovine serum albumin and UCB at a molar ratio of 1:1 resulted 6 hr later in the formation of three times as much delta bilirubin as in nonirradiated specimens. This photoinduced delta bilirubin formation increased further when the UCB/albumin molar ratio was increased to 2:1. PMID- 1941354 TI - Evaluation of four commercially available ELISA assays for the serologic diagnosis of Lyme disease. AB - We evaluated four commercially available ELISAs for detection of antibody to Borrelia burgdorferi with 21 sera from patients with clinically diagnosed Lyme disease and 89 patient control sera. Patient control sera included 28 sera from patients with rheumatoid arthritis (RA), 17 sera from patients with systemic lupus erythematosus (SLE), and 44 sera containing antibodies reported to cross react in some Lyme disease tests. The ELISAs tested (Cambridge Bioscience, Diamedix, 3M, and Zeus) detect antibodies (IgM and/or IgG) that bind Borrelia burgdorferi antigen attached to microtiter wells. Antibody reactivity in the sera from patients with clinically diagnosed Lyme disease was characterized by using Zeus immunoglobulin class-specific assays (IgM and IgG). Sensitivities in early and late Lyme disease were as follows: Cambridge and Diamedix, 57% and 100%; 3M, 57% and 93%; and Zeus, 71% and 86%. Reactivities within a patient control population were: Cambridge and Diamedix, 3%; 3M, 7%; and Zeus, 10%. PMID- 1941355 TI - Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. AB - The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin super-gene family and can be divided into two main subgroups based on sequence comparisons. In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes. The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted. Splice variants of individual genes and differential post-translational modifications of the resulting proteins, e.g., by glycosylation, indicate a high complexity in the number of putative CEA-related molecules. So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene. Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts. However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups. Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity. Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed. PMID- 1941356 TI - Detection of group A streptococci by aerobic culture and a new simplified immunoassay in three pediatric practices and a hospital laboratory. AB - Duplicate throat swabs for detection of group A streptococci were collected in three pediatric offices from 1,035 patients with symptoms of pharyngitis. In the collecting office and in the hospital laboratory, one swab from each patient was first inoculated to sheep blood agar (incubated at 35 degrees C aerobically for 2 days) and then tested for group A streptococcal antigen by using the SMART enzyme immunoassay technique (New Horizons Diagnostics Corp) incubated for up to 24 hours. Group A streptococci were recovered in culture (from one or both swabs) and serologically identified from 444 (42.9%) of the patients. Pediatric offices numbers 1, 2, and 3 detected 84.4%, 84.6%, and 82.2%, respectively, of their patients who had positive cultures (in the office and/or laboratory) by using their own culture system and 82.6%, 71.1%, and 84.9%, respectively, of these same patients by using the SMART technique. In the laboratory, SMART test sensitivity and specificity were 71.4% and 98.7%, respectively, after 5 minutes of test incubation. However, SMART test sensitivity improved to 86.5% after overnight incubation of the immunoassay and to 91.3% if the data from one defective lot of seven SMART production lots studied were excluded. SMART test results which are negative after 5 minutes of incubation should therefore be confirmed both by reincubation of the antigen test up to 24 hours and by culture. PMID- 1941357 TI - Work stress and job satisfaction in hospital-based home care. AB - The entire staff of the hospital-based home care (HBHC) at Motala (n = 35) participated in a study concerning work stress and job satisfaction. A significant number of the patients in the HBHC have advanced malignancies and most of them are terminally ill. A total of 219 questions about stress and job satisfaction were asked in a self-administered questionnaire. Only 3%-17% of the staff often or very often experienced stress factors such as high expectations, confusing orders, or lack of information. Instead, a majority stated that they often/very often experienced different aspects of job satisfaction, such as meaningfulness, security, and stimulation. Staff members stating that they often were proud/very proud of their jobs, members feeling that their skill and experience were needed, as well as staff members who often received praise from their superiors, were less prone to look for other jobs (p less than 0.01, p less than 0.05, and p less than 0.05, respectively). Those who often/very often were allowed to take initiatives of their own more often regarded their jobs as non monotonous (p less than 0.05) and stimulating to their personal development (p less than 0.001). Despite demanding jobs with severely ill patients, most of the staff gave high ratings for different aspects of job satisfaction. This positive spirit was also reflected in the exceptionally low job turnover among them. Possible explanations may be a careful selection of personnel and an organization which both stimulates the staff's own initiatives and provides support when necessary. PMID- 1941358 TI - Asthenia in cancer patients: a double-edged inflammatory response against the tumor? PMID- 1941359 TI - Psychostimulants for hypoactive-hypoalert delirium? PMID- 1941361 TI - Ascribed meaning: a critical factor in coping and pain attenuation in patients with cancer-related pain. AB - Advanced cancer is frequently associated with severe pain, and some patients suffer markedly more than others. The experience of pain is a multifactorial phenomenon involving not only sensory but also cognitive, affective, motivational, and behavioral dimensions. The latter variables were investigated within the framework of Melzack and Wall's gate control model of pain and Lazarus' coping psychology model. Quantitative measures of the McGill Pain Questionnaire, a self-report depression scale, and a coping strategy questionnaire were employed, and a face-to-face interview was conducted in which patients ascribed meaning to their pain. One hundred terminal cancer patients in the Winnipeg, Manitoba area were studied, all of whom received care at home, with one half having access to support from a hospital palliative care unit (PCU) and one half not. Analgesic medication levels were recorded and converted to a common standard. Statistical results showed that the ability to cope with the pain experience was little influenced by access to the PCU; nor was medication level a confounding variable. Variance analysis showed that the strongest impact on pain, depression, and coping scores was made by the meaning ascribed to pain by patients (p = 0.0001). The most frequently ascribed meanings were challenge (n = 30), punishment (n = 26), and enemy (n = 20). Successful pain attenuation thus depends in part on understanding the cognitive processing of pain by individual patients. PMID- 1941360 TI - Is there only one right way to die? PMID- 1941362 TI - Drug sharing and HIV transmission risks: the practice of frontloading in the Dutch injecting drug user population. AB - Injecting drug users may now be the largest group at risk for contracting HIV, mainly through the sharing of drug injection equipment (including lending, borrowing, and renting). This article presents the results of an ongoing ethnographic study into the drug-taking rituals of heroin addicts. A possible additional route of HIV contamination is presented, namely the ritual sharing of drugs through a practice termed "frontloading," which is embedded in a broader pattern of the sharing of resources among addicts. It is hypothesized that in the Netherlands this practice may be responsible for a substantial proportion of HIV spread among injecting drug users. PMID- 1941363 TI - The crack life: an ethnographic overview of crack use and sexual behavior among African-Americans in a midwest metropolitan city. AB - The use of crack cocaine and its associations with high-risk sexual behavior in view of the AIDS epidemic is reported commonly for major East and West Coast urban centers. This article describes and analyzes ethnographic data on crack use in Dayton, Ohio, a small midwestern city of less than 200,000 people. The results of 15 tape-recorded interviews are employed to sketch the basic outlines of crack use among African-Americans. A major focus is placed on analyzing the characteristics of the exchange of crack for sexual favors. High-risk behaviors for the transmission of HIV and other sexually transmitted diseases are explored. PMID- 1941364 TI - Ambivalence toward methadone treatment among intravenous drug users. AB - Interviews were conducted with a sample of jailed intravenous opioid users who were not in treatment at the time of their arrest and who were admitted to an in jail methadone maintenance program. At release, subjects were to be referred to dedicated slots in participating community methadone programs. Virtually all subjects were daily injectors of heroin and cocaine. Although the majority of subjects had previous episodes of methadone maintenance, most reported anxieties about methadone, such as bone decalcification and possible overdosing. Women and subjects who shared needles were more likely to report fears about methadone. Only 52% of the subjects stated that they intended to report to a methadone program after their release and 45% did not expect to remain in treatment for more than one year. Subjects who stated that they were not afraid of methadone, frequently injected drugs, and rarely used crack were more likely to express intentions to enroll and remain in community methadone treatment. Ambivalence toward methadone treatment may be a result of unrealistic concerns about the side effects of methadone and personal heuristics regarding the nature of addiction and the efficacy of treatment. PMID- 1941366 TI - An ethnomycological review of psychoactive agarics in Australia and New Zealand. AB - A comprehensive review is presented of the recreational and accidental ingestion of psychoactive mushrooms in Australia and New Zealand; 15 recognized species are considered from Australia and eight from New Zealand. Common epithets, potency levels, and methods of ingestion are discussed. Legal aspects involving the use of these psychoactive fungi are noted. In addition, medical and psychoactive effects of these mushrooms and treatment for psilocybian mushroom poisoning are described. Numerous case reports, with commentary, are also presented. PMID- 1941365 TI - Human hallucinogenic drug research in the United States: a present-day case history and review of the process. AB - Legitimate human research with hallucinogenic drugs, although of great theoretical and practical interest, involves daunting regulatory hurdles that have discouraged investigators from attempting such work. Using the example of the author's own application for and receipt of federal permission to administer N,N-dimethyltryptamine (DMT) to humans, this article reviews the application process, obstacles and their solutions, and the local and federal issues involved. Further human research with hallucinogens is possible if a persistent and collaborative effort is made with the relevant institutions that oversee the performance of this type of research. PMID- 1941367 TI - Attitudes about decriminalization of drug use. PMID- 1941368 TI - Substance abuse, post-traumatic stress, and ethnicity. PMID- 1941369 TI - Edmond decourtive and the first thesis on hashish: a historical note and translation. PMID- 1941370 TI - Controlled drinking, treatment effectiveness, and the disease model of addiction: a commentary on the idealogical wishes of Stanton Peele. PMID- 1941371 TI - Central nervous system (CNS) activity of two new psychoactive compounds. PMID- 1941372 TI - First, get the casual user. PMID- 1941373 TI - The medical review officer. PMID- 1941374 TI - The child with cancer and infection. I. Empiric therapy for fever and neutropenia, and preventive strategies. PMID- 1941375 TI - Nephrotic syndrome associated with acquired immunodeficiency syndrome in children. AB - We report here the cases of 15 children in whom nephrotic syndrome developed, from among 164 children (55% male, 90% black) followed in our acquired immunodeficiency syndrome clinic from 1984 through 1990. Mean age at onset of nephrotic syndrome was 4.9 +/- 2.6 years. Fourteen patients were black and one was Hispanic. Seventy-three percent of our patients with nephrotic syndrome were girls. The mean duration of clinical acquired immunodeficiency syndrome before development of nephrotic syndrome was 1.7 +/- 1.1 years. In eight patients, nephrotic syndrome appeared between 3 and 11 months after intravenous infusions of immune globulin or albumin were administered as part of a research protocol; this incidence (8/47) was higher than the incidence of nephrotic syndrome among those who did not receive intravenous infusions (7/117, p less than 0.05). Tissue for histologic examination was available for 80% of the patients, and histologic examination demonstrated mesangial hypercellularity (5 patients), focal segmental glomerulosclerosis (4 patients), minimal change disease (2 patients), and IgM nephropathy (1 patient). Deposition of one or more immunoglobulins was noted in all but one patient studied with immunofluorescence. Corresponding electron-dense deposits were seen by electron microscopy in 78% of specimens. Prednisone did not induce a remission of nephrotic syndrome in the 13 patients treated, whereas cyclosporine did so in the 3 patients to whom it was administered. Five patients were in the end stage of renal disease within 8 months. Successful maintenance peritoneal dialysis was performed in three patients, but 80% of patients have died of human immunodeficiency virus-related complications; one patient was lost to follow-up. We conclude that immune-complex deposition is consistently seen in children with human immunodeficiency virus-associated nephrotic syndrome. This nephrotic syndrome is resistant to steroid therapy, but we observed a remission of the proteinuria with cyclosporine therapy in three patients. For patients with end-stage renal disease, maintenance peritoneal dialysis may improve the quality of life. PMID- 1941376 TI - Familial hyperinsulinism: successful conservative management. AB - A large family in whom 4 of 13 children were affected with hyperinsulinism of variable severity is described. The oldest affected child required subtotal pancreatectomy to control the hypoglycemia, but the three younger children were managed successfully with prolonged conservative therapy with maintenance oral doses of diazoxide. The three affected school-age children in the family have deficits in the areas of visuomotor integration and short-term memory. The three youngest children have normal intelligence compared with four unaffected siblings; only the oldest child, who has undergone pancreatectomy, has low average intelligence (IQ80). We conclude that in infants with persistent but asymptomatic hyperinsulinemic hypoglycemia every effort should be made to treat conservatively with antihypoglycemic agents such as diazoxide for as long as possible to allow for spontaneous remission and thereby avoid pancreatectomy. PMID- 1941377 TI - Familial and sporadic hyperinsulinism: histopathologic findings and segregation analysis support a single autosomal recessive disorder. AB - We evaluated the possible genetic contribution to hyperinsulinism in a series of patients seen during the past 15 years. Of 26 families, 5 (19%) had more than one child affected (multiplex family). There were no apparent differences between patients in the 5 multiplex and 21 simplex families, clinically, biochemically, or on histologic examination of the pancreatic specimens. The families studied had a total of 63 offspring; the 26 index patients had 37 siblings, 6 of whom were affected. After four patients with hyperinsulinism caused by adenoma were excluded from the study, segregation analysis was carried out to test the data for agreement with results expected if familial and isolated hyperinsulinism represented a single disease with recessive mode of inheritance and a segregation ratio of 0.25. Excellent agreement was found between the observed number of affected siblings (20) and the expected number (19.65), with a segregation ratio of 0.254. The results were consistent with the hypothesis that in most or all cases, hyperinsulinism is inherited as an autosomal recessive disease. There was no evidence of distinct familial and sporadic types. PMID- 1941378 TI - Interval between symptom onset and diagnosis of pediatric solid tumors. AB - Lag time (the interval between symptom onset and diagnosis) was described for 2665 children with lymphoma or a solid tumor who participated in Pediatric Oncology Group therapeutic protocols from 1982 until 1988. Median lag time ranged from 21 days for neuroblastoma to 72 days for Ewing sarcoma. Significant differences in lag time were found among diagnostic groups (p less than 0.001), even after adjustment for age, gender, and race. Age was significantly associated with lag time for all diagnoses (p less than 0.05) except Hodgkin disease. Girls had increased lag times for non-Hodgkin lymphoma (p = 0.02) but decreased lag times for Ewing sarcoma (p = 0.02). Differences in lag time related to race were significant only for children with osteosarcoma (p = 0.02), for which white children had longer lag times. Type of tumor and age were strongly associated with lag time. Within diagnostic groups, age, gender, and race failed to explain more than 16% of the variance in lag time, suggesting that other factors may play more prominent roles. Further study is necessary to identify these factors and to assess the relationship between lag time, stage of disease at diagnosis, and prognosis, especially before designing early-detection interventions for childhood cancer. PMID- 1941379 TI - Thyroid function after treatment of brain tumors in children. AB - In 134 children who had been treated for a brain tumor not involving the hypothalamic-pituitary axis, thyroid function was assessed up to 24 years after treatment with cranial or craniospinal irradiation. In addition, 78 children received up to 2 years of cytotoxic chemotherapy. Of 85 children who received craniospinal irradiation, 30 (35%) had abnormalities of thyroid function, and 10 (20%) of 49 who received cranial irradiation had such abnormalities. Frank hypothyroidism developed in three children and thyrotoxicosis in one. Thirty-six children had an elevated thyroid-stimulating hormone level in the presence of a normal thyroxine level; in 16 of them the thyroid-stimulating hormone level subsequently returned to normal. Twenty-eight children who were treated between 1960 and 1970 were excluded from the analysis. Of 34 children who received cranial irradiation, five had thyroid dysfunction and 24 of 72 who received craniospinal irradiation had such dysfunction (p = 0.013). Thyroid dysfunction was present in 4 of 35 children who received no chemotherapy and in 25 of 71 who received chemotherapy (p = 0.014). Direct irradiation plus chemotherapy was more damaging than irradiation alone. These data confirm the high incidence of thyroid dysfunction when the thyroid gland is included in the radiation field. However, in a high proportion, the thyroid abnormalities are minor and revert to normal with time; life-long replacement therapy with thyroxine may be unnecessary. PMID- 1941380 TI - Management of hyperinsulinism in infants. PMID- 1941381 TI - Value of bronchoalveolar lavage in diagnosing severe respiratory syncytial virus infections in infants. PMID- 1941382 TI - Cancer risk among patients with cystic fibrosis. PMID- 1941383 TI - Ureteropelvic junction obstruction in the first year of life. PMID- 1941384 TI - Spectrum of renal anomalies in patients with Williams syndrome. PMID- 1941385 TI - Obesity and erythrocyte sedimentation rate in children. PMID- 1941386 TI - Reduction of plasma cortisol levels in childhood obesity. PMID- 1941388 TI - Significance of seizures associated with extracorporeal membrane oxygenation. AB - We previously reported a predominance of left focal motor seizures in infants receiving extracorporeal membrane oxygenation (ECMO), raising concerns about possible ischemia resulting from the right common carotid artery ligation. We therefore evaluated the neurologic and psychologic outcome at 2 years of age of all infants with ECMO-related seizures. Although 8 of 12 infants had left focal seizures in infancy, there was no lateralization of motor findings at 2 years of age; left hemiparesis was present in three of the infants and right hemiparesis in three. The developmental quotient was normal in 6 of 12 infants, low-average in three, borderline in two, and in the mentally handicapped range in one. We conclude that any ischemia resulting from carotid ligation is not great enough to produce long-term lateralizing findings but that seizures during ECMO are a risk factor for later cerebral palsy or developmental delay. PMID- 1941387 TI - Recombinant erythropoietin compared with erythrocyte transfusion in the treatment of anemia of prematurity. AB - To assess the risks and benefits of erythropoietin versus erythrocyte transfusion in the treatment of the anemia of prematurity, we randomly assigned 19 anemic preterm infants (birth weight 988 +/- 227 gm; gestational age 27.6 +/- 1.2 weeks; age 41 +/- 15 days; all values mean +/- SD) to receive either transfusion or subcutaneously administered erythropoietin (200 units/kg every other day for 10 doses). In the 10 erythropoietin recipients, corrected reticulocyte counts increased from 2% +/- 1% to 7% +/- 2% (p less than 0.001) and hematocrits increased from 27% +/- 2% to 30% +/- 4% (p less than 0.05). In the nine infants who underwent transfusion, reticulocyte counts did not increase, but hematocrits increased from 28% +/- 4% to 41% +/- 2% after initial transfusion (p less than 0.001) and had decreased to 34% +/- 5% by day 20. Signs attributed to anemia (tachycardia, apnea with bradycardia, and poor weight gain) declined in both the erythropoietin recipients and those who underwent transfusion. However, five of nine infants who underwent transfusion had symptoms within 10 to 14 days and were given further transfusions. Marrow aspiration performed after 7 to 10 days of treatment showed that infants receiving erythropoietin had greater percentages of erythropoietic precursors (p less than 0.01), greater concentrations of mature erythroid progenitors (p less than 0.001), and higher cycling rates of erythroid progenitors (p less than 0.001). The percentage of mature stored neutrophils in marrow was lower in the erythropoietin group than in the transfusion group, resulting in an inverse myeloid/erythroid ratio (0.5:1 vs 6.2:1; p less than 0.001). After 20 days, absolute blood neutrophil counts were lower in the erythropoietin recipients (1.8 +/- 0.9 x 10(3) cells/microliters) than in the infants who underwent transfusion (3.9 +/- 1.9 x 10(3) cells/microliters; p less than 0.05). Administration of erythropoietin thus stimulated erythropoiesis and relieved signs attributed to anemia; the significance of the relative neutropenia remains to be determined. We conclude that erythropoietin administration offers promise as an alternative to erythrocyte transfusion in neonates with symptomatic anemia of prematurity. PMID- 1941389 TI - Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children. AB - We determined four carnitine constituents (total and free carnitine and short- and long-chain fatty acid carnitine esters) in serum from 471 patients treated for convulsions with phenobarbital, valproic acid, phenytoin, and/or carbamazepine. The 471 patients were in eight treatment groups; four were treated with monotherapy and four with polytherapy. The means of all four carnitine constituents were significantly reduced in all treatment groups (except for free carnitine in four groups). Total carnitine was reduced by 23% to 48%, free carnitine by 9% to 45%, short-chain fatty acid carnitine by 46% to 64%, and long chain fatty acid carnitine by 6% to 29%. Patient frequency of reduction for total carnitine was 20% of all patients (10% for free carnitine), 23% of patients receiving valproate (9% for free carnitine), 36% of those receiving phenobarbital (21% for free carnitine), 12% of those receiving phenytoin (8% for free carnitine), and 8% of those receiving carbamazepine (1% for free carnitine). Only for phenobarbital was there an inverse correlation between the serum concentration of the drug and that of carnitine concentration. One patient receiving carbamazepine had a 59% reduction in the total and a 65% reduction in the free carnitine concentration and a fivefold increase in long-chain fatty acid carnitine, values similar to those seen in neonatal lethal carnitine palmitoyl transferase II deficiency. It remains to be determined whether a reduction in serum carnitine values in patients receiving anticonvulsant therapy is of clinical consequence, whether the reduction is present in some patients before the start of therapy, when and by what mechanism carnitine levels may become reduced during therapy, and whether the reduction exists in the solid tissues of these patients. PMID- 1941390 TI - Single-dose, placebo-controlled comparative study of ibuprofen and acetaminophen antipyresis in children. AB - Ibuprofen was evaluated as an antipyretic agent in 178 children (aged 3 months to 12 years) to compare dosage (5 vs 10 mg/kg), establish absolute efficacy (with a placebo control group), determine relative efficacy (ibuprofen vs acetaminophen), evaluate maximum efficacy, and identify potential confounding variables. Ibuprofen 5 mg/kg was minimally effective in children less than 6 years of age who had an initial temperature of at least 38.8 degrees C (101.9 degrees F). Ibuprofen 10 mg/kg was more effective for febrile children. The area under the curve for temperature (or change in temperature) captured the net effect of each drug and provided the best estimate for efficacy comparison during a defined period. A linear correlation between initial temperature and measures of efficacy was observed. A twofold increase in efficacy was observed for children with an initial temperature less than 38.8 degrees C. A similar effect was noted for each treatment group. Age was also found to have confounding effects on antipyretic response. A complex interaction between antipyretic response, initial temperature, and age raises questions about the pharmacodynamics of the antipyretic response. We conclude that the most important variable in antipyretic study design is initial temperature. The influence of initial temperature on the magnitude of the response to an antipyretic drug is a previously unappreciated finding with potential impact on pharmacodynamic investigations of antipyretic medications. We describe this finding as nonlinear pharmacodynamics. PMID- 1941391 TI - Randomized, double-blind, multicenter, controlled trial of ibuprofen versus acetaminophen (paracetamol) and placebo for treatment of symptoms of tonsillitis and pharyngitis in children. PMID- 1941392 TI - Paucity of renal complications associated with nonsteroidal antiinflammatory drugs in children with chronic arthritis. PMID- 1941393 TI - Membranous glomerulonephritis and chronic persistent hepatitis B in a child: treatment with recombinant interferon alfa. PMID- 1941395 TI - Perspectives on cholesterol screening programs for children. PMID- 1941394 TI - Psychosocial and behavioral factors associated with risk of sexually transmitted diseases, including human immunodeficiency virus infection, among urban high school students. AB - The main purpose of this study was to evaluate the role of multiple psychosocial and knowledge-related antecedent factors that may predict sexual and alcohol and drug use behaviors that are associated with the transmission of sexually transmitted diseases (STDs), including human immunodeficiency virus infection. Five hundred forty-four ninth-grade urban high school students were surveyed regarding knowledge, attitudes, and behaviors related to STDs and acquired immunodeficiency syndrome (AIDS). Results of multiple regression analyses indicate that higher levels of STD and AIDS knowledge were associated with lower levels of STD and AIDS anxiety (R2 delta = 0.09; p less than 0.001), fewer negative attitudes toward people with AIDS (R2 delta = 0.09; p less than 0.001), stronger perceptions of self-efficacy (R2 delta = 0.03; p less than 0.01), and stronger peer affiliation (R2 delta = 0.02; p less than 0.05). Negative attitudes toward people with AIDS were inversely related to knowledge (R2 delta = 0.08; p less than 0.001), social support (R2 delta = 0.02; p less than 0.01), and perceived self-efficacy (R2 delta = 0.01; p less than 0.05). Predictors of alcohol and drug use included perceived peer norms (R2 delta = 0.08; p less than 0.001) and strong peer affiliation (R2 delta = 0.05; p less than 0.001). The best predictor of sexual risk behavior was alcohol and drug use (R2 delta = 0.07; p less than 0.001). Lower levels of knowledge (R2 delta = 0.14; p less than 0.01) and perceived peer norms (R2 delta = 0.05; p less than 0.05) predicted nonuse of condoms. Our results indicate that several factors relate to adolescent risk for STDs: the connection between peer influence and adolescent risk behaviors, the link between alcohol and drug use and sexual risk behavior, and the role of knowledge in determining nonuse of condoms. PMID- 1941396 TI - Cow milk protein hydrolysate infant formulas not always "hypoallergenic". PMID- 1941397 TI - Bone marrow examination in prolonged fever. PMID- 1941398 TI - Treatment of shigellosis. PMID- 1941399 TI - Proteinuria and prognosis in hemolytic-uremic syndrome. PMID- 1941400 TI - Safety of loperamide in infants with diarrhea. PMID- 1941401 TI - Role of the pediatrician in promoting breast-feeding. PMID- 1941402 TI - Selenium and the very-low-birth-weight infant. PMID- 1941403 TI - Selenium absorption and retention by very-low-birth-weight infants: studies with the extrinsic stable isotope tag 74Se. AB - Measurements of dietary selenium absorption and retention were obtained after administration of a single dose of the extrinsic stable isotope tag 74Se in 20 appropriate for gestational age premature infants with birth weights between 720 and 1,630 g and gestational ages between 26 and 33 weeks. Infants were assigned randomly to receive a standard premature formula (1.34 microgram of Se/dl) or a selenium-supplemented version of that formula (2.03 micrograms of Se/dl). Each study consisted of one feeding that had been extrinsically labeled with 74Se (1.03 microgram/kg) and a timed stool and urine collection. The percent 74Se absorption was 91.2 +/- 5.4% (mean +/- SD) from the standard formula and 86.2 +/- 3.0% from the selenium-supplemented formula (p less than 0.05), but the percent of the absorbed 74Se retained was not different, i.e., 96.6 +/- 2.1% and 95.0 +/- 2.8%, respectively. The percent net absorption and net retention were also not different between the standard and selenium-supplemented formulas; net absorption was 72.7 +/- 18.1% vs. 67.8 +/- 18.8% and net retention was 57.2 +/- 17.6% vs. 53.3 +/- 20.2%, respectively. The percent 74Se absorption and true selenium absorption were significantly correlated with the percent net selenium absorption and net selenium absorption, respectively. We conclude that an extrinsically administered dose of 74Se can be used to study selenium nutrition in growing premature infants. PMID- 1941404 TI - Effect of intravenous calcium infusions on serum chemistries in neonates. AB - In 36 newborn infants admitted to the Children's Hospital of Oklahoma, we studied the hypotheses that intravenous bolus infusions of Ca as calcium gluconate over 10 min may (a) result in acute metabolic acidosis, (b) increase serum osmolality, (c) increase serum free bilirubin, and (d) decrease serum phosphorus concentrations. All infants received 18 mg/kg of elemental calcium, as either a 5 or 10% solution of calcium gluconate. Blood ionized calcium (iCa) rose significantly with i.v. bolus Ca infusion (p less than 0.005) and blood pH and serum P declined significantly (p less than 0.05) with i.v. bolus Ca infusion in infants. Serum free bilirubin was not significantly altered. Serum osmolality rose significantly from baseline with bolus infusion of Ca as a 10% calcium gluconate solution and did not change significantly with bolus infusion of a diluted 5% solution. In neonates, intravenous bolus calcium infusion (a) decreases blood pH, (b) infusion of 10% but not 5% calcium gluconate increases serum osmolality, (c) serum free bilirubin concentrations were not altered, and (d) serum phosphorus concentrations were decreased. PMID- 1941405 TI - Effect of breast feeding on the plasma cholesterol and growth of infants. AB - The effect of breast-feeding on plasma cholesterol, body weight, and body length was studied longitudinally in a large free-living cohort of infants (n = 512) from birth until the age of 1 year. Of the cohort, 21.4% were exclusively breast fed for at least 3 months, 39.3% received bottle-feeding, and 39.3% received a combination of breast- and bottle-feeding. At birth the plasma cholesterol was similar in the three groups. After 3 months the mean plasma cholesterol and proportion of hypercholesterolemic infants in the breast-fed group were significantly (p less than 0.001) higher than that of the other two groups. These differences had disappeared at the age of 1 year. Breast-fed infants weighed less at 3 and 12 months, but body length was similar to those of the other groups. These results suggest that breast-feeding elevates plasma cholesterol by a direct mechanism and that the effect persists only as long as the breast-feeding is continued. PMID- 1941406 TI - Fat absorption in premature infants: medium-chain triglycerides and long-chain triglycerides are absorbed from formula at similar rates. AB - Fat absorption from two different premature infant formulas and one full-term formula containing three different fat blends was investigated in two groups of premature infants. The first group of nine infants (gestational age, 29.1 +/- 0.88 weeks; postnatal age, 3.13 +/- 0.71 weeks) was fed alternately for 1 week each SMA preterm formula containing either high levels (50%) of medium-chain triglycerides (MCT) (6:0, 8:0, and 10:0) or high levels (86%) of long-chain triglycerides (LCT) (greater than or equal to C12). Except for fat blends, the formulas were otherwise identical. The second group of 11 infants (gestational age, 30.5 +/- 0.77 weeks, studied at a postnatal age of 4.33 +/- 0.91 weeks) was fed for 1 week a full-term infant formula, S-26, containing 98% LCT. Fat absorption (studied during a 3-day fat balance period) was similar irrespective of fat blend: 89.08 +/- 2.37% during feeding of preterm SMA, 50% MCT; 87.0 +/- 3.81% during feeding of preterm SMA, 86% LCT; and 83.00 +/- 2.89% during feeding of S-26, 98% LCT. Weight gain (grams per day) and increase in length (centimeters per day) were 23.2 +/- 1.7, 21.20 +/- 1.7, and 14.28 +/- 2.9, and 0.17 +/- 0.06, 0.16 +/- 0.04, and 0.22 +/- 0.07 during feeding of the three fat blends, respectively. Lipase activity levels in fasting gastric aspirates were higher during feeding of the LCT than the MCT formula. The possible stimulation of gastric lipase secretion secondary to long-chain fatty acid stimulation of cholecystokinin secretion might be related to the efficient digestion of formula fat, irrespective of triglyceride-fatty acid chain length.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941408 TI - The effect of sugar cereal with and without a mixed meal on glycemic response in children with diabetes. AB - The effect of sucrose consumption on glycemic control in children with insulin dependent diabetes mellitus is unclear. Eight young subjects, 7-16 years of age, with a duration of diabetes of 2-8 years participated in this study. All subjects consumed four different breakfasts--oatmeal (OM) alone, oatmeal-sucrose (OMS), oatmeal-protein (OMP), and oatmeal with protein and sucrose (OMPS)--on four different days. Addition of sucrose resulted in a slightly greater area under the tolerance curve in 50% of the subjects; however, in 38% of subjects, the area decreased. The peak glucose level was lowest for OM, but there was no statistical difference in the peak levels of the four test meals. The most significant effect on glucose response was a delay in the peak time when protein was added to the meals. Peak times for OM and OMS (mean of 38 min) when fed alone were significantly (p less than 0.05, ANOVA) shorter when compared to the peak time for OMP and OMPS (mean of 54 min). The average recovery time for OMP was longest. Other indices (tolerance index and change of rise in blood glucose) measured were not significantly different among the test meals. This study demonstrates that adding limited sucrose to OM cereal has little effect on the blood glucose response in children with diabetes. Addition of protein and fat clearly delays the glycemic response. PMID- 1941409 TI - Steatocrit test after a standard fatty meal: a new simple and sensitive test to detect malabsorption. AB - The steatocrit test, a simple semiquantitative method for determining fat content in stool, was performed after a standard fatty meal to detect malabsorption in patients with celiac disease. Thirty-seven children (mean age 2.6 +/- 2.1 years) with total atrophy of the intestinal villi and 79 controls (mean age 3.5 +/- 2.8 years) were studied. All subjects underwent a small-bowel biopsy, a D-xylose absorption test, a rapid triglyceride absorption test, and a steatocrit determination first on an uncontrolled diet and then again after a standard fatty meal. The steatocrit test after a fatty meal did not detect any false-positive or false-negative results, while the D-xylose test showed two false-negative and four false-positive results, and the rapid triglyceride absorption test found two false-negative and 23 false-positive results. We conclude that the determination of steatocrit after a standard fatty meal is a useful, simple, and noninvasive test to identify patients with total intestinal villous atrophy. PMID- 1941410 TI - Assessment of preclinical vitamin A deficiency in children with persistent diarrhea. AB - To explore the relationship between vitamin A deficiency and persistent diarrhea among young children, we studied the vitamin A status of 23 children greater than 5 years of age with persistent diarrhea by performing conjunctival impression cytology (CIC) and the relative dose-response test (RDR) as a measure of liver reserve of vitamin A. The control group consisted of 23 age- and sex-matched children who were otherwise healthy in whom CIC was performed and fasting plasma retinol values were determined. The criteria for vitamin A deficiency in CIC were paucity of goblet cells and scanty, abnormal epithelial cells. None of these children had ocular manifestations of vitamin A deficiency. Among the children with persistent diarrhea, CIC characteristic of vitamin A deficiency was found in 17 (group 1) and CIC results were normal in six (group 2). In group 1, the serum retinol levels were 1 +/- 1 microgram/dl, and RDR was 88 +/- 14. In group 2, the serum retinol levels were 8 +/- 4 micrograms/dl (p less than 0.001) and the RDR was 16 +/- 12 (p less than 0.001). In the control group, the CIC results were normal in all the children and the plasma retinol levels in these children were 19 +/- 8 micrograms/dl. In conclusion, 17 of 23 children with persistent diarrhea had abnormal CIC results, significantly low serum retinol levels, and significantly high RDR results, although they had not yet manifested xerophthalmia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941407 TI - Growth and metabolic responses in low-birth-weight infants fed human milk fortified with human milk protein or with a bovine milk protein preparation. AB - Unfortified human milk does not normally provide enough protein to secure maximal growth in low-body-weight (LBW) infants. Due to the practical difficulties in obtaining human milk protein (HMP), a bovine milk protein preparation (BMP) was designed by computer calculation to contain as close as possible the amino acid composition of the nutritionally available human milk proteins. Twenty-one AGA, LBW infants (BW of 1,180 to 1,600 g, GA of 27 to 33 weeks) were randomly assigned to be fed HM enriched either with HMP (9 infants) or BMP (12 infants). When full volume intake (170 ml/kg/day) was reached, the protein intakes were 3.6 +/- 0.5 and 3.3 +/- 0.3 g/kg/day, respectively, in the two diet groups. During the study period of 24 days, the infants achieved intrauterine or better weight gains: 32.9 +/- 3.3 g/day (17.7 +/- 1.9 g/kg/day) in the HMP group and 34.7 +/- 7.3 g/day (18.3 +/- 3.5 g/kg/day) in the BMP group. Serum urea nitrogen, acid-base status, and albumin values were normal and similar in both groups of infants. Plasma concentrations of total essential and total amino acids at the end of the study were 3,999 and 1,539 mumol/L and 3,899 and 1,422 mumol/L in the HMP and the BMP groups, respectively. The concentrations of all individual plasma amino acids were similar in both feeding groups. These results show that feeding human milk fortified with a modified bovine milk protein preparation produces satisfactory growth and a plasma amino acid profile similar to that found in LBW infants fed exclusively human milk protein at similar intakes. PMID- 1941411 TI - Urinary hydroxyproline: relationship to growth, bone mineral content, and serum alkaline phosphatase level in premature infants. AB - There is little information on urinary hydroxyproline (UHP) excretion in premature infants. We hypothesized that UHP excretion would positively correlate with growth in premature infants, and that there would be correlations between UHP excretion and serum alkaline phosphatase concentration as well as bone mineral content (BMC). Twenty-six premature infants (birth weight, less than 1,300 g; gestational age, less than or equal to 32 weeks) received one of four oral feedings. Seven received mother's own milk (HM), and eight received mothers own milk fortified with 0.85 g/dl of bovine whey, 90 mg/dl of Ca, and 45 mg/dl of P. Six and five infants received Similac, 20 cal/oz (SIM) and Similac Special Care, 20 cal/oz, respectively. Measurements of UHP, serum alkaline phosphatase, BMC (photon absorptiometry), and growth were made during the 1st 7 weeks of life. The lowest UHP excretion was in the HM group. For all infants, there was a significant correlation between UHP excretion (mg/day) and absolute weight (r = 0.64, p less than 0.001), as well as rate of weight gain (r = 0.50, p less than 0.01). The UHP excretion (milligrams per day) also correlated with absolute length (r = 0.41, p less than 0.01) and rate of gain in length (centimeters per week) (r = 0.70, p less than 0.001). The UHP excretion did not correlate significantly with BMC or serum alkaline phosphatase concentration. We conclude that UHP excretion is increased in the growing premature infant compared to older infants and adults and is a good marker for somatic growth in this population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941412 TI - The adaptive response of rectal electrolyte absorption to impaired sodium balance in young children. AB - Rectal electrolyte transport was measured in nine children (median age 160 days) with ileostomies, using a nonequilibrium dialysis technique. Rectal sodium absorption and potassium secretion were significantly higher in children with a subnormal sodium balance compared with children with a positive sodium balance. Rectal sodium absorption and potassium secretion were unchanged after ileostomy closure. These data indicate that rectal electrolyte transport in children can adapt to even modestly impaired sodium balance. PMID- 1941413 TI - Serum IgG and IgA anti-gliadin antibodies as markers of mucosal damage in children with suspected celiac disease upon gluten challenge. AB - Serum anti-gliadin antibodies (AGAs) of the IgG and IgA isotypes were determined in 17 children (mean age of 5.6 years) by means of an enzyme-linked immunosorbent assay (ELISA). All children were suspected of celiac disease. They had been on dietary treatment for at least 10 months before they were challenged with gluten. Based on jejunal biopsy findings, 10 of the 17 children had to be considered positive. The sensitivity of the measurement of AGA at 6 weeks after gluten challenge was found to be 90% for IgG, 100% for IgA, and 100% for IgG/IgA combined. The specificity for IgG, IgA, and the IgG/IgA combination was 100, 71, and 100%, respectively. Twelve weeks after gluten challenge, the sensitivity as well as the specificity of AGA determination for IgG, IgA, and IgG/IgA were 100%. It is concluded that testing both IgG AGA and IgA AGA in children suspected of celiac disease is valuable in monitoring the course of the diagnostic provocation protocol and that jejunal biopsies can be abolished. This inexpensive tool can be useful in reducing the number of intestinal biopsies. PMID- 1941414 TI - Coombs-positive hemolytic anemia preceding ulcerative proctitis. AB - A 12-year-old girl is described who developed rectal bleeding 5 months after being diagnosed as having a Coombs-positive hemolytic anemia. Colonoscopy showed that the rectal bleeding was due to ulcerative proctitis. This is the first case report of Coombs-positive hemolytic anemia preceding the onset of ulcerative proctitis in a child. PMID- 1941415 TI - Childhood protein-losing enteropathy associated with Helicobacter pylori infection. AB - Helicobacter pylori was found in a gastric biopsy specimen of a child with protein-losing gastropathy. Through erythromycin therapy, clinical and ultrasonographic recovery was associated with the disappearance of the pathogen on repeated biopsy. The association of H. pylori with protein-losing gastropathy has been reported only once in children, to our knowledge. Although the causative correlation between the pathogen and the disease has not been proven yet, we suggest that future cases of protein-losing gastropathy be studied for the presence of H. pylori and followed up by ultrasonographic investigation and urea breath test. Appropriate treatment should be given to suspected cases. PMID- 1941416 TI - Hyperplastic polyp of the stomach simulating hypertrophic pyloric stenosis. AB - We describe a rare case of hyperplastic polyp of the stomach having its clinical origin in the neonatal period and initially stimulating hypertrophic stenosis of the pylorus. After this neoformation, which almost completely obstructed the pylorus, was endoscopically removed, vomiting ceased and a rapid weight gain was observed. It is known that tumors are a rare cause of gastric outlet obstruction if compared with hypertrophic stenosis of the pylorus. However, our experience suggests that in the case of atypical symptoms, the investigations should be extended, especially to endoscopic examination of the upper digestive tract. PMID- 1941417 TI - Cystic fibrosis and diabetes mellitus: interactive or idiopathic? PMID- 1941418 TI - Nucleotide stability in infant formula. PMID- 1941419 TI - Impression cytology with transfer: a novel nutritional index. PMID- 1941420 TI - Distribution of synapses in Hirschsprung's disease. PMID- 1941422 TI - A developmental history of the Society of Pediatric Psychology. AB - Presented history of the field of pediatric psychology in general and, more specifically, the development of the Society of Pediatric Psychology. Review began with 1896 concepts of Lightner Witmer and followed with 1960 activities by Logan Wright which led to the formation of the Society. The developmental phases of the Society are described with respect to goals, publications, financial status, training issues, and awards established. Present activities of liaisons with numerous outside organizations and agencies and regional conferences are detailed. PMID- 1941421 TI - Autoimmune polyendocrine candidiasis syndrome with associated chronic diarrhea caused by intestinal infection and pancreas insufficiency. PMID- 1941423 TI - Cautions in using the Child Behavior Checklist: observations based on research about children with a chronic illness. AB - The Child Behavior Checklist (CBCL) and the related instruments, the Teacher's Report Form (TRF) and Youth Self-Report (YSR), are frequently used in research assessing the behavioral adjustment of children. This paper describes some issues relevant to children with a chronic physical illness that should be considered when using these instruments. Salient problems include (a) possible bias in interpreting data concerning physical symptoms; (b) limited sensitivity to identify mild adjustment problems of the sort most often encountered in children with chronic physical illnesses; and (c) incomplete and potentially misleading assessment of social competence. When using these instruments investigators should also be aware of several general methodologic issues before collecting, analyzing, and interpreting data regarding children with chronic illnesses. PMID- 1941424 TI - Cognitive abilities and achievement status of children with myelomeningocele: a contemporary sample. AB - Designed study as a conceptual replication of Shaffer, Friedrich, Shurtleff, and Wolf (1985). Intelligence, school achievement, and perceptual motor skill data from 73 children with uncomplicated myelomeningocele were examined to determine their deviation from test norms. The respective impact of shunting and functional motor level was also assessed. The sample as a whole functioned below WISC-R and VMI norms. On the WRAT, deviation from the norms was evident only for the Arithmetic subtest. Partial replication of the Shunt X Motor level interaction reported by Shaffer et al. (1985) was obtained. Limitations of small-sample studies are discussed. PMID- 1941425 TI - Psychology in primary health care: effects of brief targeted therapy on children's medical care utilization. AB - Evaluated the impact of psychological treatment for 93 children (ages 1-15) with common behavior, toilet, school, and psychosomatic problems. Children and parents, who were members of a health maintenance organization, had 1-6 visits to a primary care-based psychological consultation service. Individualized treatment was guided by problem-specific behavioral protocols. Parent outcome and behavior checklist ratings indicated improvement or resolution for 74% of children and high satisfaction with the psychological service. Children's use of medical services, especially acute primary care visits, was reduced during the year after treatment; a matched comparison group's use was unchanged. Addressing children's unmet mental health needs reduces medical care utilization. A primary health care model of psychological services provides an integrated system for serving the health and mental health needs of children. PMID- 1941426 TI - Psychosocial adjustment among pediatric cancer patients: a multidimensional assessment. AB - Identified types and frequencies of psychological difficulties manifested by pediatric oncology patients and child-, family-, and illness-related correlates of adjustment. Parents of 48 children with cancer, 4 to 17 years of age, completed the Personality Inventory for Children (PIC). Analysis of mean PIC scores indicated that the children had a high frequency of somatic concerns and problems in academic functioning. Similar mean PIC profiles were obtained for children across gender, age, and diagnostic groups. Overall, 52% of the children had profiles with two or more clinically significant problem areas. Children's adjustment was associated with gender, social competence, and parental coping. Boys exhibited significantly more problems than did girls. Children whom teachers rated as less socially competent and whose parents reported few effective coping responses exhibited greater difficulties in adjustment. PMID- 1941427 TI - Cognitive effects of childhood leukemia therapy: a case for four specific deficits. AB - Prophylactic treatment of the central nervous system (CNS) with cranial irradiation and antineoplastic drugs has made childhood acute lymphoblastic leukemia (ALL) a survivable disease, but at the same time there have been many reports of iatrogenic effects, including deficits in cognitive functioning. Previous research suggests a particular effect on the Freedom from Distractibility factor of the WISC-R, memory, and attention. These particular abilities are tested in a group of 43 ALL survivors, with comparisons against solid tumor as well as sibling controls. The results indicate that four cognitive processes are affected by CNS prophylaxis for ALL: short-term memory, speed of processing, visuomotor coordination, and sequencing ability. Younger children have a more severe speed of processing deficit and children treated with a less rigorous protocol appear to be slightly less affected generally. The specific cognitive deficits found are related to neurological evidence on both theoretical and empirical grounds. Results suggest that children who have received CNS prophylaxis are able to learn, but may be slower to acquire new material and may benefit from bimodal presentation. PMID- 1941428 TI - Preparation of children for emergency medical care: a primary prevention approach. AB - Increased emergency room use and the resulting rise in pediatric visits have prompted interest in psychological aspects of pediatric emergency care. This study evaluated the efficacy of a multicomponent hospital program designed to prepare children for emergency room visits. In Phase 1, 148 kindergarteners completed measures of medical fears and knowledge at pretreatment, posttreatment, and a 4-week follow-up. Program attenders had significantly fewer medical fears and higher medical knowledge at posttest and follow-up than control children. The program was more effective for black than white children. In Phase 2, 51 high fear children from Phase 1 were selected randomly to attend a medical examination in an emergency room. No effects for program emerged on the observational distress measures or physiological arousal. Phase 2 children showed significantly increased medical knowledge at follow-up compared to children who did not receive the medical exam. PMID- 1941429 TI - An epizootic of cutaneous zygomycosis in cultured dwarf African clawed frogs (Hymenochirus curtipes) due to Basidiobolus ranarum. AB - Morbidity and mortality approaching 100% occurred in dwarf African clawed frogs (Hymenochirus curtipes) from a culture facility in central California. Moribund frogs exhibited preference for a terrestrial environment rather than their normal aquatic environment. Affected animals had a slight pallor of the integument but were otherwise grossly unremarkable. Microscopic examination revealed a fungal infection of the integument primarily characterized by the presence of surface and intra-epidermal conidia. Skin cultures of the infected animals yielded an organism identified as Basidiobolus ranarum, based on the formation of conidia in culture with internal cleavage to form sporangiospores. The organism was transmitted to healthy frogs by co-habitation with infected frogs but not by short-term immersion exposure of healthy frogs to homogenized broth cultures of the fungus. Benzalkonium chloride at 2.0 mg l-1 was efficacious in controlling the infection. Although Basidiobolus species are normally found in the intestinal tract of amphibians, the severity of this epizootic indicates that B. ranarum may be an important pathogen of amphibians reared in culture facilities. PMID- 1941430 TI - Ultrastructure of the pseudo-cleistothecia produced by the Trichophyton mentagrophytes complex. AB - The internal structure and the formation processes of pseudo-cleistothecia in Arthroderma vanbreuseghemii, a member of the Trichophyton mentagrophytes complex, were observed by light and electron microscopy. The structure of pseudo cleistothecia, obtained by single spore culture of A. vanbreuseghemii, developed as a clump of hyphae producing microconidia which increased gradually in size. Echinulations appeared on the surrounding hyphae, which developed into peridial hyphae with characteristic constrictions. These pseudo-cleistothecia contained the microconidia. During the mating of A. vanbreuseghemii and Arthroderma simii, pseudo-cleistothecia structures developed from organs similar to the gametangia. These pseudo-cleistothecia contained interwoven hyphae but no microconidia. PMID- 1941431 TI - 'Antibiobodies': antibiotic-like anti-idiotypic antibodies. AB - Pathogenic micro-organisms such as Candida albicans may be susceptible to the activity of antimicrobial products like yeast killer toxins due to the presence of specific cell wall receptors for these agents. Anti-idiotypic antibodies (anti Ids) were produced that competed for these receptors with the yeast killer toxin of a strain of Pichia anomala. We report here that affinity chromatography purified anti-Ids may kill C. albicans cells in vitro which are susceptible to the activity of the yeast killer toxin, as well as P. anomala killer cells which are obviously immune to their own toxin despite possessing specific cell wall receptors which can be detected by indirect immunofluorescence with anti-Ids. We propose that these conceptually new antimicrobial immunoglobulins acting as antibiotics be called 'antibiobodies'. PMID- 1941433 TI - The effect of dermatophyte species and density of infection on the pathology of ringworm. AB - In this study we have measured the mean hyphal length as a function of the density of infection in skin surface biopsies from patients suffering from infection with different species of dermatophyte. The tissue response in the epidermis and dermis of these patients was evaluated for the degree of eczematization (epidermal thickening, spongiosis and dermal infiltrate) in periodic acid Schiff stained histological sections, employing visual analogue scales. There was no correlation between mean hyphal density and the degree of eczematization. PMID- 1941432 TI - Intrahyphal hyphae in corneal tissue from a case of keratitis due to Lasiodiplodia theobromae. AB - Lasiodiplodia theobromae, a recognized plant pathogen, was isolated in culture from a case of human mycotic keratitis. Chemotherapy with a variety of azoles was unsuccessful and the lesion was removed surgically. Electron microscopy of thin sections of the excised corneal tissue revealed several examples of intrahyphal hyphae, a unique process described previously in in vitro cultures of various zoopathogenic fungi. We believe this to be the first report of the presence of intrahyphal hyphae in parasitized animal or human tissue. The demonstration of this process in vivo is thought to be consistent with the hypothesis that intrahyphal hyphae might represent an attempt by the invading fungus to survive in an otherwise unfavourable environment. PMID- 1941434 TI - Liposomes as cyclosporin A carriers: the influence of ordering of hydrocarbon chains of phosphatidylglycerol liposomes on the association with and topography of cyclosporin A. AB - The addition of cholesterol and stearylamine to liposomes prepared from phosphatidylglycerol containing saturated and unsaturated fatty acids was studied to determine the effect on binding of cyclosporin A (CsA). It was found that liposomes containing phosphatidylglycerol-stearylamine-cholesterol in the molar ratio of 7:2.25:2 had the highest capacity to bind CsA (36.7 mol of phospholipid to 1 mol of CsA), while binding of CsA to phosphatidylglycerol liposomes, phosphatidylglycerol-stearylamine liposomes, or phosphatidylglycerolcholesterol liposomes was significantly lower (342.9, 174.4 and 422.3 mol of phospholipid to 1 mol of CsA, respectively). The binding of CsA to all these liposomes was compared with their order parameters, obtained by electron spin resonance spectroscopy using 5-nitroxide stearic acid spin probe. It was found that increased binding of CsA paralleled the increased ordering of hydrocarbon chains achieved by addition of cholesterol to these liposomes. When liposomes were prepared from pure dimyristoylphosphatidylglycerol (DMPG), 30.7 mol of DMPG were required to bind 1 mol of CsA. The topography of CsA in phosphatidylglycerol liposomes was established by using 5-nitroxide stearic acid as a spin probe. In DMPG liposomes, CsA was found in hydrocarbon chains adjacent to the polar head group, while in liposomes prepared from phosphatidylglycerol containing mixed fatty acids, CsA was associated with the polar head group region without penetrating the hydrocarbon chains of phosphatidylglycerol. PMID- 1941435 TI - Preparation and performance evaluation of plain proliposomal systems for cytoprotection. AB - Plain liposomal systems composed of soyabean lecithin, cholesterol and stearylamine were formulated using various approaches. The prepared products were characterized and evaluated for their cytoprotective performance against the necrotizing NSAID's (i.e. aspirin and phenylbutazone). Liposomes derived from proliposomes (effervescent granules based) demonstrated the best cytoprotective activity and physical and stability characteristics. This system was shown to be superior. An increased availability of regular and small sized liposome born phospholipids to the damaged mucosal systems accounted for its better and enhanced performance. PMID- 1941436 TI - Controlled release from cylindrical microstructures. AB - Microtubules formed from diacetylenic phosphatidyl-cholines can be made rugged and solvent resistant through electroless deposition of metals (Rudolph et al. 1990). Once dried tubules can capture a range of materials by capillary action when added to a hydrating medium, thus retaining and controlling the release rates of these materials. We report the encapsulation in tubules of a mixture of tetracycline, epoxy monomers and polymers and their in vitro release kinetics in both dynamic and static environments. PMID- 1941437 TI - Semi-permeable microcapsules for cell culture: ultra-structural characterization. AB - Microcapsules made from alginate-poly(L-lysine)-alginate membranes have been studied as vehicles for cell culture in a number of laboratories. We have examined their permeability, robustness and ultrastructure in detail. Permeability to globular proteins could be controlled by using poly-lysine of different mean MW in their construction. However, this parameter also affected the degree to which microencapsulated living cells leaked out of the capsules during and after preparation. Poly-lysine of low MW produced a relatively permeable and robust membrane whereas a high MW produced capsules with the reverse characteristics. A MW of 22,000 appears to be optimal in forming robust capsules which are relatively impermeable to high MW species such as immunoglobulins. The structure of the semipermeable membrane was investigated by electron microscopy and found to be complex but entirely consistent with the data on protein permeability and cell leakage. Microcapsules were not disrupted by gentle treatment with trypsin or chelating agents but dissolved with the addition of heparin, sodium dodecyl sulphate or sodium hydroxide. Empty microcapsules implanted into the peritoneal cavity of rats elicited a host cellular reaction but remained intact for at least three months. PMID- 1941438 TI - Preparation of enteric-coated microspheres of Mycoplasma hyopneumoniae vaccine with cellulose acetate phthalate: I. Formation condition and micromeritic properties. AB - The solvent evaporation method was employed to encapsulate Mycoplasma hyopneumoniae vaccine (MHV) using cellulose acetate phthalate (CAP) as an enteric coating material. Glucose was used as a diluent. The effect of some factors, such as encapsulating temperature, surfactant concentration, mechanical agitation and CAP concentration on the formation condition, particle size distribution, morphology, surface topography and antigen content of MHV microspheres, was investigated. The result indicates that the optimal operating conditions were: encapsulating temperatures, 20 degrees C; stirring speed, 400 rpm; span 80 concentration, 0.6; and 8 per cent of CAP concentration, 30 ml. The optimal condition can be used to prepare the desirable microspheres. The content uniformity of MHV microspheres was also indicated. PMID- 1941439 TI - Preparation and performance of cross-linked agar encapsulated activated charcoal (CAAC-III). AB - A technique is described to encapsulate activated charcoal for hemoperfusion to be used in an artificial liver support. Spherical activated charcoal was coated with agar and shaped in organic solvent, as well as cross-linked by epichlorohydrin (40-50 degrees C). The product withstood autoclaving at 121 degrees C for 0.5 hours, and had a good adsorption ability for compounds with molecular weight ranging from 113-5200. The adsorption kinetic showed pore diffusion limitation to compounds of small molecular weight, and film diffusion limitation to compounds of large molecular weight. Microparticles of charcoal release were greatly reduced, and within the permissible range according to the requirements in the U.S. Pharmacopeia (1985). PMID- 1941440 TI - Mixed-wall microcapsules made of cross-linked proteins and polysaccharides: preparation and properties. AB - Microcapsules were prepared through an interfacial cross-linking process using terephthaloylchloride and applied to mixtures of a protein (human serum albumin or gelatin) and a polysaccharide. Their properties were compared with those of microcapsules prepared from the protein alone. Morphological characteristics of mixed-walled microcapsules were often modified, as seen by light and electron microscopy. Otherwise, they appeared to be more resistant to digestive media: they were gastroresistant, and their degradation time in pancreatin was prolonged upon raising the amount of polysaccharide. Moreover, the lysis time was shown to depend on the nature of the polysaccharide: microcapsules prepared from acidic polysaccharides at pH 9.8 were hydrolyzed faster. Lastly, the resistance increased upon decreasing the polymers/acylchloride ratio, or upon raising the reaction pH. Encapsulation assays were carried out with sodium salicylate, which was incorporated with a high efficiency. Mixed-walled microcapsules allowed a prolonged release of the tracer in vitro. As compared with protein microcapsules, the release profiles of batches prepared with hydroxyethylstarch exhibited only slight modifications of the initial part of the curve, while a significant burst effect was observed with carboxymethylcellulose-containing microcapsules. PMID- 1941441 TI - Liposomes as a model for studying the effect of UV radiations on biomembranes. AB - Sonicated vesicles prepared from lecithin and rat brain or liver lipid extracts were exposed to ultraviolet radiations (UV), and the formation of thiobarbituric acid reactive products of lipid peroxidation were followed. Long range UV (UVA) was found to be more active than short UV (UVC). Incorporation of different amounts of pure Cu-Zn superoxide dismutase, caused a consistent increase in thiobarbituric acid reactive products in the case of UVC, but with UVA, higher doses were inhibitory. Incorporation of alpha-tocopherol into the vesicles, helped to entrap more calcium ions within the dialysed liposomes, but UV exposure did not significantly influence calcium leakage. Liposomes appear to be convenient in vitro models for studying the phototoxic effects mediated through active oxygen species, membrane damage and altered calcium fluxes. PMID- 1941442 TI - A new technique for the encapsulation of water insoluble drugs using ethyl cellulose. AB - A new technique for encapsulation of water insoluble drugs has been developed utilizing ethyl cellulose as a wall forming material. Ethyl cellulose was dissolved in a water immiscible, volatile organic solvent, containing sulphadiazine as a model drug. This dispersion was emulsified into an aqueous bentonite suspension and phase separation was induced by solvent evaporation. The effect of bentonite concentration, core to coat ratio, organic solvent, speed of agitation and temperature was studied with respect to the microcapsule size and size distribution, drug content, in vitro release and surface characteristics. PMID- 1941443 TI - Effect of nanoparticles on transdermal drug delivery. AB - The purpose of the present study was to assess by in vitro means the effect of poly (methylmethacrylate) nanoparticles and poly (butylcyanoacrylate) nanoparticles on transdermal drug delivery. Methanol and octanol were chosen as test permeants. In order to distinguish between thermodynamic effect and those due to biological consequences, two different membranes were employed, i.e., full thickness hairless mouse skin and silicone elastomer sheeting (175 microns). It is evident that poly (methylmethacrylate) nanoparticles and poly (butylcyanoacrylate) nanoparticles increase the permeability of methanol through hairless mouse skin by a factor of 1.2-2. The permeability of lipophilic octanol is either unaffected by nanoparticles or decreases as a function of nanoparticle concentration depending on the lipophilicity of the polymer material. PMID- 1941444 TI - Study of some improved shellac derivatives as microencapsulating materials. AB - Shellac was chemically modified to alter its permeability and to prevent its 'after hardening'. Various shellac derivatives such as with succinic anhydride, phthalic anhydride, ethylenediamine and myristic acid were prepared. Salicylic acid granules were coated and evaluated for flow properties, moisture absorption and release characteristics before and after ageing. These derivatives imparted better flow properties and showed excellent ageing properties. PMID- 1941445 TI - Encapsulation of drugs into large unilamellar liposomes prepared by an extemporaneous method. AB - The method we developed for extemporaneous preparation of large unilamellar liposomes (Philippot et al. 1984) was applied to the encapsulation of 12 different antibiotic, anti-asthmatic and anti-inflammatory drugs. The behaviour of these drugs, during encapsulation, assigns them to one of the three classes: hydrophilic, hydrophobic or both. Alone, the first type of compound gave an appreciable encapsulation. However, the entrapment yield depended on the respective charges of the liposome and the drug. The amphiphile molecules tested are permeant and thus did not stay inside the liposomes. Only one of the hydrophobic drugs analysed associated with the liposome membrane lipids with a good yield. PMID- 1941446 TI - Distribution of liposome-incorporated carboxyfluorescein in rabbit eyes. AB - The penetration of liposomal drugs into rabbit eyes was investigated using 6 carboxyfluorescein (6-CF) as a water-soluble model substance. It was possible to incorporate 4.1 mg 6-CF into the aqueous space of 1 ml of liposomes produced with reverse phase technique. In comparison to aqueous 6-CF, liposomal 6-CF reached extremely high concentrations in all parts of the eye, and was released slowly over many days. The highest concentration of liposomal 6-CF (55 micrograms g-1) was found in the sclera 30 minutes after injection. The corresponding value of aqueous 6-CF was 5 micrograms g-1. After 7 days, liposomal 6-CF was still detectable at the subconjunctival injection location as well as in the sclera, retina, chorioid and cornea. In clinical examination and fluorescence photography no side effects were observed except for moderate and transitory conjunctivitis. In conclusion, liposomes are appropriate drug carriers for delivery of drugs to the posterior eye segment. This method is, however, limited to drugs with chemical properties which permit incorporation in pharmacologically relevant amounts. PMID- 1941448 TI - Central venous catheter-related complications in newborns and infants: a 587-case survey. AB - In an attempt to identify factors determining central venous catheter-related complications in newborns and infants, 587 cases have been retrospectively analyzed. Attention has been paid to the influence of the incidence of babies' body weight, site of insertion, and technique of placement of the catheter and the material used, ie, silicone (SI) or polyurethane (PU). Overall complications occurred in 28% of the catheters with 2 deaths due to cardiac tamponade. Mechanical complications happened in 22% of the catheters, including dislodgement (11.6%), extracorporeal perforation (5.3%), and obstruction (5%). Septic complications occurred in 4% catheters, including proven bacteriemia (2.5%), abscess at the entry site (1%), and isolated fever (0.8%). Clinically evident caval thrombosis occurred in 1% of the catheters. Overall complications were significantly higher when the body weight was lower than 2,500 g (P less than .01) due to a significantly higher incidence of septic complications (P less than .05). When a proximal site of placement of the catheter was used, both septic and mechanical complications were more frequent than in the distal approach (P less than .01). The incidence of complications was similar in surgically and in percutaneously placed catheters as in SI and PU catheters. Nevertheless, fatal complications occurred only in PU catheters, leading us to avoid the choice of such material in newborns and small infants. PMID- 1941447 TI - Eudragit E microspheres containing bacampicillin: preparation by solvent removal methods. AB - Eudragit E microspheres containing bacampicillin hydrochloride were prepared by solvent evaporation and solvent extraction methods. Three different systems of solvents were used: methyl acetate, acetone and methanol/liquid paraffin. The success of the procedures depended mostly on the lipophilicity of the solvent. The particle size of microspheres was determined by sieve analysis. The results showed that the average size of microspheres is influenced greatly by the type of solvent. Scanning electron microscopy was used for observation of the shape of microspheres. Microspheres prepared by the solvent evaporation method in systems with acetone and methyl acetate were all of a regular spherical shape. The surface of all other microspheres were folded. The influence of magnesium stearate content in microspheres was also studied in terms of different methods, solvents and processing conditions. PMID- 1941449 TI - Management of pediatric laryngotracheal stenosis. AB - In the past 6 years, 40 children underwent surgery for laryngotracheal stenosis; 32 by the external approach and 8 by endoscopic CO2 laser. Twenty-seven children (67%) were less than 5 years old at the time of treatment and 80% of the stenoses (n = 32) corresponded to an etiology that is secondary to endotracheal intubation and/or tracheotomy. By grading the stenoses according to the amount of narrowing of the lumen, the authors emphasize the interest of conservative treatment (endoscopic for grade I [less than 70%, n = 8], and treatment by external surgical methods for grade II [70% to 90%, n = 13], grade III [90% to 99%, n = 14], and grade IV [total obstruction, n = 5]). At this time, the most commonly used technique is laryngotracheoplasty with costal cartilage interposition. In this series, 88% of the patients were successfully decannulated. As for the treatment of stenosis in infants, the authors describe their recent experience of laryngotracheofissure in 7 patients as an alternative to either tracheotomy in cases of difficult extubation or laryngotracheoplasty when the child is underweight. PMID- 1941450 TI - Predicting outcome following pulmonary resection in cystic fibrosis patients. AB - A small subset of cystic fibrosis (CF) patients develop pulmonary disease primarily limited to one lobe or lung segment requiring prolonged recurrent hospitalizations with intensive medical therapy. Although surgery has been advocated for patients who do not respond to medical therapy, very little is known about criteria for selection of patients who might benefit from resection of the involved parenchyma. In an attempt to further define criteria for pulmonary resection in these patients, we retrospectively reviewed our experience at Tulane Medical Center over the past 10 years. Fourteen patients with CF, ranging from 3 to 30 years of age, underwent 17 pulmonary resections. Indications for surgery were persistent lobar or pulmonary atelectasis and bronchiectasis requiring multiple hospitalizations and unresponsive to medical therapy (n = 13), bronchopleural fistula (n = 2), or hemoptysis not responding to medical therapy or selective embolization (n = 2). Thirteen lobectomies and four pneumonectomies were performed. Only two resections were on the left side and 11 right upper lobectomies were performed. Postoperative hospitalization ranged from 5 to 21 days (mean, 8.5 days). Preoperative pulmonary function tests showed widely divergent function in these patients. Forced expiratory volume (FEV1) ranged from 11% to 88% whereas forced vital capacity (FVC) ranged from 20% to 100% of predicted values. Oxygen saturation ranged from 86% to 99%. Although there was no significant difference in preoperative and postoperative FVC or O2 saturation, there was a significant (P less than .003) decrease in the postoperative FEV1. In the 12 surviving patients followed for at least 1 year, there was also a significant reduction (P less than .001) in the number of hospitalizations required due to pulmonary exacerbations from an average 2.2 admissions per year (range, 0.44 to 3.5 admissions per year) to 1.1 admissions per year (range, 0 to 8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941451 TI - Tracheoaortopexy via midline sternotomy in tracheomalacia. AB - Symptomatic tracheomalacia associated with congenital tracheoesophageal fistula requires active treatment. When symptoms are severe, consideration should be given for surgical correction. Aortopexy via a lateral thoracotomy and tracheopexy via an anterior cervical approach have been described. We present two patients with extensive tracheomalacia who benefited from combined tracheoaortopexy via a midline sternotomy approach. PMID- 1941452 TI - Persistent third branchial apparatus. AB - Neck sinuses, cysts or fistulae arising from the third branchial apparatus, have seldom been reported. Between 1979 and 1989, 16 cases were diagnosed as persistent third branchial apparatus based on a fistula open or in proximity to the pyriform sinus. There were 8 boys and 8 girls whose ages ranged from newborn to 13 years. Esophagogram was performed in 6; 4 showed a fistula tract leading to the pyriform sinus. Others were demonstrated at surgery. The main presentations were suppurative thyroiditis (5), lateral neck fistula (5), cyst (3), mass (1), abscess (1), and esophageal stricture (1). This was interpreted as a spectrum of disease that in the newborn may present as a cyst, and later in childhood as a fistula in the lower neck or recurrent suppurative thyroiditis if the fistula ends in the thyroid gland. It is imperative to search for this internal communication to the pyriform sinus to make a correct diagnosis and to avoid development of esophagocutaneous fistula postoperatively. With more awareness of this disease entity, the noted incidence should increase. PMID- 1941453 TI - Oral suction in infants. AB - This is a description of a simple sucking sump catheter for continuous saliva removal. PMID- 1941454 TI - Diagnosis of H-type tracheoesophageal fistula. AB - A study was made of the diagnostic aspects of 11 cases of congenital tracheoesophageal fistula without atresia (H-fistula) seen in the 17 years 1971 through 1988. The features of aspiration with feeding were present from birth in all cases, and yet the diagnosis was often delayed. The results emphasise the complimentary diagnostic roles of contrast esophagogram and rigid open-tube endoscopy. The latter not only yields a high diagnostic rate but is necessary for evaluation of associated congenital anomalies of the aerodigestive tract. PMID- 1941456 TI - Total gastric transposition: an alternative to esophageal replacement in children. AB - Total gastric transposition was performed in 21 children as an alternative procedure for esophageal replacement. The age at the operation ranged from 15 months to 11 years. Half of the children were less than 2 years old. Fifteen patients had esophageal atresia. The stomach was passed toward the neck either through the esophageal bed (6 cases, with concomitant blunt esophagectomy without thoracotomy) or the retrosternal route (15 cases). There was one death in the early postoperative period secondary to an anastomotic leak and acute mediastinitis in a case of pharyngogastric anastomosis. Three other patients developed cervical leak with spontaneous closure but this ultimately led to a late anastomotic stricture (more than 6 months) requiring endoscopic dilatation. Only one child needed more than three attempts of endoscopic dilatation. None of these patients required surgical revision. The mean follow-up was 60 months (range, 10 to 122 months). Despite bulky atonic intrathoracic stomach occurring in some children, only two patients developed regurgitation and symptoms of poor gastric emptying. There were neither early nor late respiratory problems. Excellent and good functional outcome were achieved in 85% and 15% of the patients, respectively. Two patients have not undergone a weight catch-up phase. The majority of the children have been between the 20th and 80th percentile for weight. Five children remain below the 20th and two below the 5th percentile. The remarkably low morbidity and mortality combined with satisfactory functional results indicate that the total gastric transposition is a safe and easy alternative surgical procedure for esophageal replacement in children. PMID- 1941455 TI - Acquired tracheoesophageal fistula in infancy and childhood. AB - Acquired tracheoesophageal fistula (TEF) is a rare entity in the pediatric age group. We report two pediatric patients with acquired TEF caused by shells of pistachio nuts. In both patients the primary operation did not resolve the problem and a second intervention for recurrent fistula was needed. The special nature of acquired TEF, particularly the one described herein, requires delayed surgical intervention and meticulous separation of the respiratory and alimentary tracts by an intercostal muscle flap. PMID- 1941457 TI - Esophageal pH monitoring for gastroesophageal reflux: a United Kingdom study. AB - Esophageal pH monitoring is the accepted standard for the investigation of gastroesophageal reflux (GER) in adults. A postal questionnaire was sent to 912 United Kingdom paediatric physicians & surgeons. Five hundred forty-seven (61%) replied, with 124 (22.7%) currently using the technique, mostly in conjunction with barium swallow and/or esophagoscopy. The use of pH monitoring to quantify GER was also accepted in principal as being the best determinant of reflux by a further 186 (34%), but as yet was unavailable in their hospitals. Pediatricians were also questioned as to their management of children with GER. The majority were treated medically with a variety of antireflux medication, with only 237 (42%) referring cases for surgery. PMID- 1941458 TI - The mean duration of gastroesophageal reflux during sleep as an indicator of respiratory symptoms from gastroesophageal reflux in children. AB - The coexistence of gastroesophageal reflux (GER) and respiratory symptoms has been reported in children, but identifying a reliable indicator of reflux-induced respiratory symptoms has been difficult. The mean duration of reflux episodes during sleep (ZMD), extracted from a 18- to 24-hour esophageal pH recording, has been presented previously as a reliable correlate of respiratory symptoms caused by GER in infants. To reexamine the accuracy of the ZMD we report 519 consecutive children with respiratory symptoms (aged 1 week to 15 years) who were referred for documentation of GER by 18- to 24-hour esophageal pH monitoring. Follow-up information was obtained on 388 patients 1 to 115 months later (mean, 23 months). From the follow-up information, 259 children could be reliably classified; 128 as having reflux-related and 131 as having reflux-unrelated respiratory symptoms. None of the 131 children with reflux-unrelated respiratory symptoms had a prolonged ZMD (greater than 3.8 minutes). In comparison, 119 of the 128 children (93%) with reflux-related respiratory symptoms had a prolonged ZMD (P less than .001). The nine children who had a normal ZMD and improvement in their respiratory symptoms with the successful control of GER had advanced esophagitis (n = 4), central apnea (n = 3), or associated disorders in which respiratory symptoms improved with the avoidance of oral feedings (n = 2). In conclusion, the ZMD was confirmed to correlate directly with both the presence and absence of respiratory symptoms caused by GER in children. PMID- 1941459 TI - The risk of sudden infant death from gastroesophageal reflux. AB - Gastroesophageal reflux (GER) has been a suspected cause of infant deaths and sudden infant death syndrome (SIDS). We examined our 10-year experience with 499 consecutive infants 6 months of age or less who had extended (18 to 24 hours) esophageal pH monitoring performed to evaluate for GER. The data extracted from the esophageal pH records included the pH score, the pattern of GER (type I, II, or III), and the mean duration of reflux during sleep (ZMD). All infants were followed to determine the occurrence and cause of death during the first year of life. Of the 19 deaths found in the series, three were classified as SIDS and two were in-hospital deaths caused by reflux-induced aspiration. All five of these infants who died had a prolonged ZMD (greater than 3.8 minutes) and received either basic medical (n = 4) or no (n = 1) antireflux therapy. Four infants also had the type I pattern of GER. There was a 9.1% (4/44; 95% confidence limits, 2.5% to 21.7%) incidence of reflux-related or SIDS deaths in infants with type I GER and a prolonged ZMD who were treated nonoperatively, compared with none (0/83, P = .03) in the same group of infants treated with antireflux surgery. The incidence of SIDS was higher in infants with type I GER and a prolonged ZMD who were treated nonoperatively (3/44, 6.8%) compared with all other infants treated nonoperatively (0/265, 0%; P = .003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941460 TI - Evaluation of Nissen fundoplication in neurologically impaired children. AB - The value of performing Nissen fundoplication in neurologically impaired children is a controversial issue. To evaluate the benefit of fundoplication in these children, hospital records were reviewed for 77 children who underwent fundoplication for gastroesophageal reflux (GER). Fifty-two children were neurologically impaired; 25 children had no neurological impairment. Impaired children had significantly fewer hospital admissions (1.8 v 0.7; P less than .005) and total days of hospitalization (36 v 14; P less than .005) during the first postoperative 6 months, compared with the immediate preoperative 6-month period. Normal children had fewer hospital admissions and days postoperatively, but the difference was not significant. Impaired children with preoperative failure to thrive (FTT had significantly increased average monthly weight gain over the first 6-month period postoperatively, compared with preoperative growth rate (3.0% v 0.9% of total body weight; P less than .05). Average monthly weight gain at 1 and 2 years postoperatively was not significantly different from preoperative values for impaired children. Growth rate of normal children with FTT did not change significantly postoperatively. Symptomatic relief was comparable in the normal and impaired children. Perioperative mortality was 0% in the normal children and 6% in the impaired children. This study demonstrates that Nissen fundoplication in neurologically impaired children with GER can be performed safely, reduces the frequency of hospitalization, and improves short term weight gain. PMID- 1941461 TI - The surgical approach for reconstruction of the sternal and epigastric defects in children with Cantrell's deformity. AB - Children with Cantrell's deformity manifest a midline defect of the lower sternum and epigastrium. A surgical technique is described that uses the lowermost sternocostal cartilages in reconstructing the defected sternum and simultaneously reapproximating the rectus abdominis muscles in the middle line for repair of the epigastric defect. Solid cardiac protection and superior cosmetic results were obtained without the use of foreign prosthetic material. PMID- 1941462 TI - The fundal pile: bleeding gastric varices. AB - Bleeding from esophageal varices is a common cause of major upper gastrointestinal tract blood loss in children with portal hypertension but usually ceases spontaneously or is satisfactorily managed by nonoperative measures. Massive hemorrhage from gastric fundal varices may be difficult to control with compression and sclerotherapy; in these cases, a direct surgical approach may be indicated. Since 1984, 27 children have undergone aggressive injection sclerotherapy for bleeding esophageal/gastric varices. Nine (6 with portal vein thrombosis) bled from gastric fundal varices. In 5 of these, medical management and sclerotherapy failed to control the acute bleed. In all 5 there was "rupture" of a large gastric fundal varix or "pile" and bleeding was controlled at emergency laparotomy by underrunning the varices through a high anterior gastrotomy. Four have subsequently been successfully managed by continued sclerotherapy and one patient with cirrhosis has died of liver failure. In 3 of the survivors both esophageal and gastric fundal varices have been completely obliterated. No further life-threatening hemorrhage has occurred in any case during a follow-up period of 1 to 5 years. Bleeding from gastric varices is more common than previously recorded and more difficult to control by nonoperative management, including injection sclerotherapy. In uncontrolled hemorrhage from gastric varices, surgical underrunning offers a means of providing initial control. Thereafter, the inevitable variceal recurrence may be successfully treated with sclerotherapy. PMID- 1941463 TI - Failure of duplex sonography to diagnose hepatic artery thrombosis in a high-risk group of pediatric liver transplant recipients. AB - Excellent correlation between angiographic findings and duplex sonography has been previously reported in the diagnosis of hepatic artery thrombosis (HAT), the most common technical complication of pediatric orthotopic liver transplantation (OLT). We now report a significant incidence of false-negative sonograms, ie, hepatic artery reported as patent but thrombosed on subsequent angiography. HAT was diagnosed in 10 of 57 pediatric OLT recipients evaluated prospectively by duplex sonography. In 5 patients HAT was diagnosed only by angiography even though arterial wave forms were observed on duplex sonography. Selective angiography demonstrated extensive collateral vessel formation arising from the superior mesenteric artery, the celiac axis, or both. The 5 patients shared very similar clinical courses marked by relapsing bacteremias with multiple enteric organisms, associated with focal infarctions of the liver. Four of the grafts had difficult arterial reconstructions and 3 of 5 had segmental bile duct dilation. We conclude that duplex sonography has proven to be a valuable screening tool in evaluating hepatic artery patency but must be correlated with angiography studies in a high-risk group of pediatric transplant patients characterized clinically by relapsing bacteremia and radiographically by false-negative duplex examinations. PMID- 1941465 TI - Primary anastomosis in apple-peel bowel syndrome. AB - During a 15-year period, 12 infants with apple-peel bowel were treated; the first 4 by initial enterostomy with delayed anastomosis and the remaining 8 by primary anastomosis. All four infants in the enterostomy group required parenteral nutrition, compared with only six of the eight who had a primary anastomosis. Seven of the eight infants treated by primary anastomosis were in hospital for less than 50 days, (however, the remaining child was an in-patient for over 2 years, but did suffer from short-bowel syndrome with only 17 cm of small intestine). In comparison, all four of the enterostomy group were hospitalised for between 70 and 175 days. All twelve patients survived. PMID- 1941464 TI - Spontaneous, isolated intestinal perforations in neonates with birth weight less than 1,000 g not associated with necrotizing enterocolitis. AB - From January 1986 through December 1988, we have seen 7 cases of isolated intestinal perforation in 250 infants with birth weights less than 1,000 g (3% incidence) without histological or clinical evidence of necrotizing enterocolitis (NEC). Patients had a mean birth weight of 670 g, gestational age of 25.1 weeks, and sustained a perforation at a chronological age of 10.4 days. No infants had been fed. A definite, blue-discolored abdomen was the only consistent clinical sign (n = 7). Free intraperitoneal air on radiograms was rarely observed (n = 1). Abdominal ultrasounds (n = 3) and metrizamide contrast studies (n = 3) were not diagnostic. The presence of an umbilical artery catheter (7/7), falling hematocrit (6/7), thrombocytopenia (5/7), and a positive diagnostic paracentesis were most commonly found. In 6 of 7 patients, this perforation was associated with coagulase-negative staphylococcal sepsis. Surgical or histological diagnosis showed focal perforation in either the terminal ileum (n = 4) or the transverse and descending colon (n = 3). Survival was 3 of 7; 2 patients died of intracranial hemorrhage and 2 died of Candida sepsis. We conclude that (1) intestinal perforation can occur in the absence of NEC; (2) bluish discoloration of the abdomen is the most reliable clinical finding; and (3) perforation may be associated with coagulase-negative staphylococcal infection. PMID- 1941466 TI - Experience with intestinal lengthening for the short-bowel syndrome. AB - Patients with the short-bowel syndrome frequently develop dilated intestinal segments that may lead to impaired motility and malabsorption. Although intestinal tapering alone improves motility, the intestine can be lengthened as well. We reviewed our experience with six children undergoing intestinal lengthening to improve intestinal absorption secondary to the short-bowel syndrome. The procedure was performed by dissecting the vessels along the mesenteric border and dividing the intestine longitudinally with a stapler. Five patients were receiving total parenteral nutrition (TPN) and one was becoming malnourished with enteral feedings alone. Bacterial overgrowth was documented in four patients and abnormal liver function in three patients. The intestinal segments were dilated up to 10 cm in diameter and remnant length ranged from 15 to 79 cm. Segments 5 to 25 cm in length were divided, resulting in an average increase in length of 52%. Necrosis of one of the divided limbs necessitated resection in one patient. Follow-up ranged from 2 to 84 months. TPN has been discontinued in four patients and avoided in another. Symptomatic improvement occurred in all patients. We feel the tapering and lengthening procedure should be considered in patients with symptomatic, dilated intestinal segments in whom the need for TPN may potentially be obviated. PMID- 1941467 TI - Posterior transposition of anterior ectopic anus. AB - A method of posterior transposition of anterior ectopic anus is described in which the ectopic anus is incorporated in one flap of a Z-plasty. When the flaps are transposed the anus is brought into its normal anatomical position with the added advantages that the mucocutaneous junction and part of the innervation and the blood supply are preserved. The results of 24 girls treated with this technique are presented. In spite of a high incidence of sepsis resulting from less than ideal operative conditions, the repair remained intact. PMID- 1941468 TI - Giant hemangioma of the arm associated with cardiac failure and the Kasabach Merritt syndrome in a neonate. AB - We report a neonate who presented within hours of birth with severe congenital cardiac failure, thrombocytopenia, and consumption coagulopathy, caused by a massive hemangioma of the left arm. Initial treatment with glucocorticoids, platelet and clotting factor replacements, and cardiovascular support failed to control these hemangioma effects and amputation was avoided only when axillary artery ligation and an intermittent pneumatic compression device, manufactured in this hospital, achieved control of this lesion and hastened its subsequent resolution. The treatment of such lesions is reviewed, emphasizing individualized treatment protocols, and stressing that such lesions and their effects, cannot be regarded as variants of a single disease entity when planning management. PMID- 1941469 TI - Primary lesser saphenous vein aneurysm in a child. AB - True primary venous aneurysms are rare. This is the first report of such an aneurysm involving the lesser saphenous vein. Though most often a medical curiosity, such lesions can result in serious morbidity and even mortality. Because of their rarity they are often misdiagnosed. Salient features pertaining to classification, diagnosis, and treatment are reviewed. PMID- 1941470 TI - In utero arterial embolism from renal vein thrombosis with successful postnatal thrombolytic therapy. AB - Thromboembolic events in the pediatric age group occur most commonly in neonates, and newborns of diabetic mothers are particularly at risk. We report a newborn with right renal vein and inferior vena cava thrombosis who apparently embolized across the foramen ovale antenatally with resultant right brachial artery occlusion. The baby was delivered by cesarean section from an insulin-dependent diabetic mother. At the time of birth, there was severe right arm ischemia with absent brachial and radial pulses. There was clinical evidence of distal embolization with a "trash" lesion of the distal right middle finger as well as a midforearm area of full-thickness skin loss. Ultrasound demonstrated a right renal vein thrombosis and a 95% occlusion of the inferior vena cava. Regional urokinase therapy was instituted through a lower extremity vein with a 5,000 U/kg bolus and then 5,000 U/kg/h continuous infusion. Twelve hours of infusion of urokinase led to clinical resolution of the right arm ischemia, with return of pulses. Follow-up ultrasound showed the right renal vein thrombosis and inferior vena cava clot to be completely resolved. The right middle finger and forearm lesions subsequently have healed primarily. We report this as a case of in utero arterial embolization with successful postnatal therapy using regional urokinase infusion. PMID- 1941471 TI - Successful use of a vascularized intercostal muscle flap to seal a persistent intrapleural cerebrospinal fluid leak in a child. AB - The diagnosis and management of a persistent intrapleural-dural cerebrospinal fluid fistula following excision of a large mediastinal ganglioneuroma with intraspinal extension is reported. Use of a vascularized intercostal muscle flap to close the dural fistula was curative in this 4-year-old patient. PMID- 1941472 TI - Spontaneous rupture of a noninfected urachal cyst. AB - Spontaneous rupture of a noninfected, asymptomatic urachal cyst has not been previously reported. Thus, the following case report is of interest. PMID- 1941473 TI - Increased intraabdominal pressure and anuria in the newborn. AB - Elevated intraabdominal pressure as a cause of anuria in the critically ill newborn with ascites should be considered after hypovolemia and other causes of intrinsic renal disease or obstruction have been excluded. In the rare patient with ascites who develops anuria, paracentesis should be considered if urine output cannot be established. PMID- 1941474 TI - Esophageal atresia, distal tracheoesophageal fistula, and an air shunt that compromised mechanical ventilation. PMID- 1941475 TI - Pediatric extracorporeal membrane oxygenation in posttraumatic respiratory failure. AB - The leading cause of death in the pediatric population in the United States is trauma. A retrospective review of patients treated with extracorporeal membrane oxygenation (ECMO) for traumatic respiratory failure was performed. Eight children were treated at the Ochsner Medical Foundation and additional data on six children were available from the National Registry. Six children developed respiratory failure as a result of blunt trauma and eight as a result of near drowning. Standard venoarterial ECMO was used with a circuit very similar to that used in neonatal ECMO. Vascular access was via the common carotid artery and the internal jugular vein. Ventilatory support was weaned to minimal settings during ECMO. Central hyperalimentation and systemic antibiotics were used in all of the cases. Four of six children survived in the blunt trauma group; three of eight children survived in the near drowning group. Although significant conclusions cannot be drawn from a small group of patients the average pre-ECMO PO2 for survivors was 87 mm Hg, whereas for nonsurvivors the average PO2 was only 46 mm Hg. Ventilatory support for both groups was not remarkably different, and the average PCO2 was lower in the nonsurvivor group. The cause of death in this group of patients is usually multisystem organ failure. In the four patients treated at Ochsner who did not survive, all had positive blood cultures and presumed systemic sepsis. ECMO has been demonstrated to be very successful in neonatal respiratory failure. Predicting mortality and morbidity in pediatric respiratory failure has been more difficult.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941476 TI - Pulmonary edema and fluid mobilization as determinants of the duration of ECMO support. AB - The physiological variables that govern recovery of pulmonary function during neonatal extracorporeal membrane oxygenation (ECMO) remain poorly understood. We hypothesized that pulmonary hypertension (PHN) resolves soon after starting ECMO and that neonatal weight gain, pulmonary edema, and fluid mobilization are major determinants of recovery of pulmonary function and the ability to decrease ECMO support. To evaluate this, 17 consecutive neonates requiring ECMO for severe respiratory failure were reviewed. PHN was studied by daily echocardiography to assess the direction of ductal shunting. To evaluate fluid flux, pulmonary function, and edema during ECMO, we measured body weight, urine output, and ECMO flow every 12 hours. To evaluate pulmonary edema, serial chest radiographs obtained every 12 hours were randomly reviewed and scored by two radiologists with a semiquantitative chest radiograph index score (CRIS). By 25% of bypass time, PHN had resolved in all patients. However, at that time, weight had increased to 9.16% +/- 1.78% above birth weight, and the CRIS was 44% worse than the value just prior to ECMO. From 25% time on bypass, as urine output increased, patient weight and CRIS progressively decreased, allowing ECMO support to be weaned. At the time of discontinuation of ECMO support, weight had decreased to 2.0% +/- 1.3% above birth weight, and urine output remained steady at 3.0 +/- 0.3 mL/kg/h. Within 24 hours of stopping ECMO, the CRIS showed a 58% improvement compared to maximal scores during ECMO. We conclude that PHN decreases early in ECMO and that edema and its mobilization are important determinants of the improvement in pulmonary function and duration of ECMO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941477 TI - Congenital diaphragmatic hernia, extracorporeal membrane oxygenation, and death: a spectrum of etiologies. AB - Extracorporeal Life Support Organization (ELSO) registry data show increased mortality in congenital diaphragmatic hernia (CDH) infants compared with other extracorporeal membrane oxygenation (ECMO) indications. To test the hypothesis that death might be related to various clinical parameters, retrospective data collection was solicited on 175 ECMO-related CDH deaths from 41 American ECMO centers (ELSO Registry 1980 through 1989). Data capture forms were received on 100 of 175 infants representing 29 of 41 centers. After review of all available material, a predominant cause of death was assigned. Other diagnoses were given secondary status. We analyzed arterial blood gas values at 6, 3, and 1 hour pre ECMO, as well as at the time of highest recorded PO2 (preductal and postductal) and lowest recorded PCO2, and correlated these findings with predominant cause of death. The relationship between individual variables and cause of death was assessed by t test. Multivariate analysis was performed by using a stepwise discriminate procedure. The most common predominant causes of death were brain death (29%), pulmonary hypertension (25%), and pulmonary hypoplasia (17%). Correlation of arterial blood gas values at 6, 3, and 1 hour pre-ECMO with predominant causes of death established the following statistically significant associations (P less than .05): (1) pulmonary hypoplasia and low PO2 at 6 hours pre-ECMO; (2) brain death and low pH at 1 hour pre-ECMO; and (3) pulmonary hypertension and high HCO3- at 1 hour pre-ECMO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941478 TI - Congenital diaphragmatic hernia: predictors of severity in the ECMO era. AB - Infants with congenital diaphragmatic hernia (CDH) demonstrate a wide range of anatomic and physiologic abnormalities, making it difficult to compare the efficacy of new forms of therapy such as extracorporeal membrane oxygenation (ECMO) among institutions. This study was undertaken to determine whether any predictors of severity could be identified in the ECMO era. The charts of all patients with CDH treated at this institution since 1984, when ECMO became available. (n = 110), were reviewed. Infants were considered high risk and included in this study if they presented with respiratory distress within the first 6 hours of life (n = 94). In order to focus on predictors of pulmonary insufficiency, patients who died of nonpulmonary causes or had other significant congenital anomalies were excluded from this review, leaving 59 patients for analysis. All the infants during this period had intensive pharmacological and ventilatory support. When needed, ECMO was offered postoperatively from 1984 to 1987, and preoperatively from 1987 to the present. Forty-five of 59 had a best postductal PO2 (BPDPO2) greater than 100 mm Hg, and 41 of these responders survived (91%). Fourteen patients had a BPDPO2 less than 100 mm Hg and only one survived (7%) (P = .0001). Mean BPDPO2 between survivors with or without ECMO, and nonsurvivors were also significantly different (P = .001). To incorporate ventilatory information, an oxygenation/ventilation index was devised: [OVI = PO2/(mean airway pressure x respiratory rate) x 100]. Differences in OVI between these three groups were also significant. When analyzing the data by the method proposed by Bohn (PCO2 v VI), no correlation between ventilatory parameters and outcome was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941479 TI - The irreducible ovary: a true emergency. AB - The management of a child with an irreducible ovary remains inconsistent in pediatric surgical centers. An informal survey of senior pediatric surgeons and an extensive review of the literature showed a prevailing view that the trapped ovary is not at significant risk of vascular compromise. Two recent cases prompted a review of our experience from 1984 to 1989, during which 1,699 children with inguinal hernias underwent operation, 386 (23%) of whom were girls. Fifteen girls (4%) had irreducible ovaries present at the time of operation and in 4 of the 15 (27%) the ovary was twisted and infarcted. Two of the 4 girls were known to have an irreducible ovary prior to the day of operation--1 was noted 2 months earlier and 1 was noted 1 month earlier. At the time of the initial diagnosis, neither patient had physical findings of vascular compromise of the ovary. In the other two girls, evidence of an infarcted ovary was present when the hernia was first diagnosed and an emergency operation was performed. A 27% incidence of torsion and strangulation of irreducible ovaries appears to be high, but reports of strangulated ovaries have been reported in 2% to 33% of other series. The normal anatomy is altered when an ovary is trapped in a hernia sac, and these changes make torsion more likely. Although an irreducible ovary is not at great risk of compression of its blood supply, this report identifies a significant risk of torsion. This risk warrants treating the asymptomatic irreducible ovary as any other incarcerated hernia--as a true emergency. PMID- 1941480 TI - Indium 111 oxine-labeled leukocytes for early diagnosis of ischemic enterocolitis. AB - The feasibility of the use of indium 111 oxine-labeled autologous leukocytes for the diagnosis of ischemic enterocolitis in vivo was examined in an experimental model of ischemia in dogs. A 30-cm segment of small intestine was devascularized by ligating the arteries and veins from the last arcade in 7 dogs. A sham operation was performed in 3 control dogs. 111In oxine-labeled autologous white blood cells were infused 3.5 hours after operation. Anterior and lateral nuclear scanning was performed at 6 and 24 hours postinfusion with a gamma camera equipped with a low-energy magnifying multihole collimator. The animals were killed after 24 hours. The gross and microscopic appearance of the bowel was evaluated. The radioactivity in the serial specimens of the bowel was measured. In vivo scans were positive (ie, increased uptake in the bowel loop) in all dogs with intestinal ischemia at 6 and 24 hours. No significant uptake was noted in control dogs. Rectilinear scan of the bowel removed at autopsy showed a correlation between the area of infarction and tracer accumulation. In addition, there was a progressive decrease in uptake of 111In oxine from the center of the ischemic lesions to the periphery. Forty percent of the total radioactivity was measured at the center of the lesion, whereas only 6.5% was present at 22.5 cm from the center. Thus the ratio between the ischemic and normal tissue was 10:1 (range, 6.5 to 16). These studies demonstrate that 111In oxine-labeled autologous white blood cells can be used for the diagnosis of ischemic enterocolitis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941481 TI - Colonic strictures following successful medical management of necrotizing enterocolitis: a prospective study evaluating early gastrointestinal contrast studies. AB - This is a prospective study of 50 patients with neonatal necrotizing enterocolitis (NEC) treated successfully by medical means. They were all screened with an upper gastrointestinal (GI) contrast study after 14 days of healing and prior to establishment of feeding. Thirty-six patients (72%) with normal upper GI examinations responded well to a graduated increase in feeding. Another 5 (10%) with questionable areas on their upper GI examination had a normal follow-up contrast enema. Feeding was successfully established in this group of infants also. The remaining 9 patients (18%) had demonstrable strictures in both contrast studies. After elective resection of strictures with restoration of intestinal continuity, they were also fed successfully. No delayed strictures were seen in any of the patients. We propose that this method of evaluation is safe, efficient and reliable in the diagnosis of strictures that develop in patients recovering from NEC. PMID- 1941482 TI - Experimental necrotizing enterocolitis: the role of polymorphonuclear neutrophils. AB - Polymorphonuclear neutrophils (PMNs) play an important role in inflammation. Activated PMNs adhere to the vascular wall and release reactive oxygen radicals and enzymes, producing vascular injury. In the present study, we investigated whether PMNs play an important role in the pathogenesis of experimental necrotizing enterocolitis (NEC). NEC was induced in rats using platelet activating factor (PAF, 1 microgram/kg) and bacterial endotoxin (LPS, 1 mg/kg) intravenously. Neutropenia was accomplished by parenteral injection of Vinblastine (VB, 0.75 mg/kg) 4 days before the experiment to deplete the total white blood cell (WBC) and neutrophil counts. The animals were divided into 4 groups: (1) 1 microgram/kg PAF; (2) 1 mg/kg LPS; (3) 1 microgram/kg PAF + 1 mg/kg LPS; and (4) PMN depleted, 1 microgram/kg PAF + 1 mg/kg LPS. Combined administration of PAF and LPS produced prolonged hypotension (blood pressure 53.5 +/- 13.8 mm Hg at 2 hours), leukopenia (4,062 +/- 497.4), hemoconcentration (hematocrit 44.5% +/- 1.1%), reduced intestinal perfusion (74% +/- 13.3%), and segmental bowel necrosis. However, in VB-treated animals combined PAF + LPS induced only mild hypotension (84.3 +/- 9.2 mm Hg at 2 hours) and no hemoconcentration. In these animals the intestinal perfusion was normal, no bowel necrosis was observed, and the intestinal myeloperoxidase activity (.0034 +/- .0017 U/g tissue) was significantly lower than that of the nondepleted group (.0075 +/- .0012 U/g tissue). We conclude that the presence of neutrophils and/or neutrophil products play a major role in the pathogenesis of NEC. PMID- 1941483 TI - Early hemodynamic indicators of gram-negative sepsis and shock in an infant pig model. AB - To assess the hemodynamics of early shock and to determine to what extent hemodynamic indicators of sepsis and shock can be predictive, we evaluated data from several series of experiments (including 136 piglets) in which animals were subjected to fecal-Escherichia coli peritonitis-induced septic shock. Serial measurements of 39 parameters were obtained and their values taken at baseline, at hyperdynamic sepsis, and at shock were compared by analysis of variance. Piglet weights ranged from 1.2 to 7 kg (mean, 3.5) and ages ranged from 5 to 29 days (mean, 15). Of the 39 parameters assessed, 9 (CO*, CI*, SVI*, LVSWI*, SVR*, a-vDO2, VO2, O2 delivery*, and CaO2*) proved valuable as indicators of sepsis and shock. Of these parameters, seven (*) can be measured or calculated by noninvasive techniques and easily can be determined in human neonates. Serial determinations of these hemodynamics in high-risk neonates may be able to accurately predict gram-negative sepsis and shock before these entities are otherwise clinically apparent. PMID- 1941484 TI - Evaluation of mortality in surgical neonates over a 10-year period: nonpreventable, permissible, and preventable death. AB - The mortality pattern and causes of death in surgical neonates were evaluated over the period of 1980 through 1990 in order to assess whether any deaths might have been prevented. In the study period 1,010 neonates were admitted, 104 of whom died (10%). These 104 neonates formed our study population. The Clinical Classification System (CCS) and the Therapeutic Intervention Scoring System (TISS) were used to assess the severity of illness. All 104 nonsurvivors were seriously ill (CCS 3 and 4; TISS greater than 20). The mortality pattern was classified in three groups. Group A (nonpreventable death) included 56 deaths, 48 of which were due to the underlying disease. The other 8 patients died of a nonpreventable complication of treatment. Eleven of the patients in group B (permissible death) had (multiple) congenital anomalies associated with chromosomal anomalies. Three of them were not treated and in the other 8 treatment was initially started but later withdrawn. In most of the other 14 patients further treatment was withdrawn because of serious postoperative complications or inoperable cardiac anomalies. Group C (preventable death) consisted of 23 patients. Six of 10 had irreversible brain damage due to prolonged hypoxemia. In the other 13 patients of group C, death was due to sepsis acquired in the postoperative period and treated inadequately. Staphylococcus epidermidis was the most frequent isolated pathogen (7/13). PMID- 1941485 TI - Corticosteroids in the management of unresected plasma cell granuloma (inflammatory pseudotumor) of the lung. AB - The case of a 10-year-old girl with plasma cell granuloma of the lung and an associated hypergammaglobulinemia is reported. A thoracotomy and biopsy were done. Total resection would have required a pneumonectomy. She was treated with an immunosuppressive course of prednisone, which resulted in a reversal of the infiltrative process and the hypergammaglobulinemia. PMID- 1941486 TI - Sequential changes in relative liver function assessed by 99mTc-HIDA scintigraphy after auxiliary heterotopic liver transplantation in dogs. AB - Auxiliary heterotopic liver transplantation (HLT) was used to achieve functional repair in a dog model with an inborn error of metabolism. For the interpretation of the results, information on separate liver function is essential when a normal host liver is also present. We developed a radionuclear method to quantitate the relative contribution of each liver to the total uptake of intravenously (IV) injected 99mTc-HIDA. The HLT was performed between 20 mismatched pairs of dogs from two different strains. Four surgical procedures were used. After autopsy the outcome of the premortem HIDA-scan was compared with the wet weight of the graft and the host liver. A good linear correlation was noted between the relative contribution of the uptake and weight of the graft to the total HIDA uptake and total liver weight. Therefore, the relative contribution of an auxiliary heterotopic liver graft to the total liver function can be quantitated with a 99mTc-HIDA scan. With this technique, changes in relative function after an HLT under various flow conditions can be sequentially followed. PMID- 1941487 TI - Fecal fat, cyclosporine, and alpha 1-antitrypsin for assessment of small bowel function following transplantation. AB - Many factors affect the integrity of transplanted small bowel. These include ischemic preservation and immunologic injury as well as the division of intestinal lymphatics during transplantation. This study was undertaken to evaluate the recovery of fat absorption in transplanted small bowel in syngeneic rats. Orthotopic transplantation of the total small bowel with resection of the native intestine was performed. The experimental (n = 11) and a pair-fed, sham operated control (n = 8) groups were fed a 50% kcal corn oil semipurified diet. Studies of cyclosporine (CSA) absorption, maltose absorption, dietary fat, and fecal alpha 1-antitrypsin (FA1AT) excretion in transplanted animals were performed preoperatively and at 15, 30, and 50 days postoperatively. There was no significant difference in the weight change or fat and maltose absorption in experimental animals compared with control animals at any time point. Peak serum CSA levels were lower at day 15 in transplanted animals than in controls (P = 0.006) and improved but remained lower than those in controls at days 30 and 50 (P = 0.017). FA1AT excretion was increased on postoperative day 15 (accompanied by a decrease in body weight) and returned to control levels at days 30 and 50. Transplanted isogeneic rats had weight recovery and fat and carbohydrate absorption similar to those of controls. Transplanted animals had a protein losing enteropathy measured by FA1AT at day 15 that resolved by 30 and 50 days, respectively. CSA absorption showed a much more gradual return to control levels and remained abnormal at 50 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941488 TI - Successful closure of intestinal fistulae in an infant using the somatostatin analogue SMS 201-995. AB - Enterocutaneous and other gastrointestinal fistulae create tough challenges with respect to wound care, nutrition, and strategy for closure. SMS 201-995 is a long acting somatostatin analogue that has been effective in the treatment of adult enteric fistulae. The use of SMS 201-995 as an adjunct in the successful closure of intestinal fistulae in an infant is reported. This newborn infant developed a high-output enterocutaneous fistula and multiple enteroenteric fistulae after an intestinal resection for necrotizing enterocolitis. Copious fistulae output led to extensive wound breakdown, dehydration, and failure to thrive. Despite traditional management with bowel rest, total parenteral nutrition, antibiotics, and wound care, the high-output fistulae persisted unabated. On postoperative day 12, SMS 201-995 was started at 0.7 microgram/kg subcutaneously twice daily and gradually increased to 2.5 micrograms/kg. Within 2 days of SMS 201-995 therapy, the fistulae drainage had decreased from 62 mL/kg/d to 36 mL/kg/d, a 42% decrease from pretreatment levels. By day 8 of treatment, all fistulae had closed. After 14 days of treatment, the wound had healed and the infant was gaining weight. An upper gastrointestinal examination showed a patent ileostomy and no fistulae. Feeding was initiated, SMS 201-995 was discontinued without significant ileostomy output increase, and successful ileostomy closure took place 4 weeks posttreatment. Furthermore, the infant had no demonstrable side effects from the drug. Use of this drug should be considered in the treatment of other infants with complex, recalcitrant gastrointestinal fistulae. PMID- 1941489 TI - Endoscopy-guided balloon dilatation of esophageal strictures and anastomotic strictures after esophageal replacement in children. AB - This study evaluates the safety, efficacy, and technical problems of the new technique of endoscopy-guided balloon dilation (EGBD) in the treatment of strictures of the esophagus and its replacement. Between 1986 and 1990, the authors treated 33 children (aged 3 weeks to 20 years) with EGBD; 18 had esophageal strictures (primary esophageal atresia repair, 13; reflux esophagitis, 5), 13 had anastomotic strictures after esophageal replacement (colon, 12; stomach, 1), and 2 had caustic strictures. The majority (23 of 33) had previously failed to respond to conventional bouginage (mean, 11.2 sessions; range, 1 to 32 sessions). EGBD was performed using flexible endoscopy and flouroscopic screening under general anesthesia. Endoscopy identified and resolved the errors or uncertainties of preoperative contrast studies in 7 patients, 5 of whom had colon interposition. EGBD was achieved in all 31 patients with esophageal or replacement strictures; the mean number of EGDB procedures per patient was 2.1 (range 1 to 7). Symptomatic relief was excellent in 24 and moderate in 7 patients. Both patients with caustic strictures had esophageal perforation from EGBD (excessive inflation, 1; false passage of guide wire, 1). Patients who had experienced both conventional bouginage and EGBD noticed less pain with EGBD and resumed eating sooner. The authors conclude that EGBD is safe and effective for treating esophageal and replacement strictures but not caustic strictures. PMID- 1941490 TI - The application of solvent-processed human dura in experimental tracheal reconstruction. AB - To evaluate the role of solvent-processed human cadaveric dura in experimental tracheal reconstruction, anesthetized piglets underwent an elliptical excision of a four-ring segment of the trachea. Twelve animals were randomly divided into two equal groups: in group I, the resected trachea was rotated 180 degrees and sutured into position; in group II, the resected trachea was replaced with dura. The animals were extubated after the operation, and endotracheal stents were not used. Tracheal dimensions were recorded, and tissues were evaluated for mechanical compliance (percent elongation/displacement). Histology of the grafts was characterized by fibrosis and granulation tissue, and there were no distinguishing features between groups. The data suggest that solvent-processed human dura has compliance and patency comparable to those of autologous free grafted trachea and that it may prove useful as an adjunct to reconstructive tracheal surgery in infants. PMID- 1941491 TI - Surgical management of stage III and IV neuroblastoma: resection before or after chemotherapy? AB - Local control is vital for long-term survival for patients with stage III neuroblastoma, and although cure is difficult, ultimate success in stage IV neuroblastoma will necessitate control of the primary tumor as well as effective therapy of the metastases. The proper timing of surgical resection of the primary tumor is uncertain. Patients with stage III and IV neuroblastoma treated from 1977 to 1988 were retrospectively reviewed as to whether the resection was performed before or after chemotherapy. Complications assessed include significant blood loss, damage to adjacent organs, and delays before postsurgical chemotherapy could be given. Sixty patients were treated primarily at the authors' institution: 18 with stage III and 42 with stage IV disease. Chemotherapy consisted of combinations of nitrogen mustard, adriamycin, dacarbazine (DTIC), cisplatin, vincristine, and cyclophosphamide (MADDOC). Nine patients with stage III neuroblastoma underwent initial resection of the primary tumor before receiving chemotherapy. Three had complications, all with excessive blood loss (0.57, 2.0, and 3.0 times the estimated total blood volume [TBV]). One patient had renal infarction, and another had regrowth of the tumor before chemotherapy could be administered 35 days after surgery. There were no complications in the eight secondary explorations, four of which were complete resections. All had viable tumor in the resected specimen. Eleven of the 42 stage IV patients had primary resections, 5 of whom had complications: colocutaneous fistula, unilateral renal necrosis, chylothorax, and excessive blood loss (1.3 and 2 TBV). None of the 18 patients with delayed resection after 3 to 12 courses of chemotherapy had surgical complications with complete (14 patients), near complete (2 patients), or subtotal resections (2 patients).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941492 TI - Aggressive surgery combined with intensive chemotherapy improves survival in poor risk neuroblastoma. AB - One hundred eighteen children with metastatic (Childrens Cancer Study Group [CCSG] stage IV), extensive regional (stage III), or stage II neuroblastoma with N-myc amplification received an intensive chemotherapeutic regimen of cis platinum, etoposide, doxorubicin, and cyclophosphamide combined with persistent aggressive attempts at complete primary tumor resection. Fourteen patients were unevaluable and 42 left the study to be placed on bone marrow transplant protocols. The remaining 62 children were evaluated in detail. Complete excision was eventually accomplished in 39 patients (63%), 23 of whom are disease-free survivors after 8 to 47 months (median, 20 months). Twenty-three patients underwent partial excision or biopsy of their lesion and only 6 are alive without evidence of disease (P = .0011). Timing of surgery or site of tumor did not influence surgical outcome. N-myc oncogene expression could not predict which lesions would be completely resectable. Surgical complications occurred 21% of the time but the impact on the clinical course and chemotherapy administration was minimal. The ipsilateral kidney was removed with the tumor in 18 cases, 14 of which were during complete resection. Twelve of these children are disease-free survivors. With new intensive chemotherapy capable of eliciting an effective response from primary and metastatic neuroblastoma, aggressive surgical approaches for complete tumor resection are warranted and can be expected to improve patient outcome. PMID- 1941493 TI - Microvascular reconstruction of major arteries in neonates and small children. AB - Arterial injuries in neonates and children under 2 years of age, although relatively uncommon, should be treated by prompt exploration and reconstruction using microvascular techniques. In the past, a reluctant attitude has prevailed in cases involving neonates or infants because of small vessel caliber and the problem of spasm. We reviewed our experience with 9 nonreplantation, arterial reconstructions in children under 2 years of age. The most frequent age at reconstruction was 1.0 month and extended from the immediate newborn period to 24 months of age. All patients were at risk for tissue necrosis. Eight children sustained iatrogenic injuries related either to invasive catheter manipulation (n = 6) or operative transection (n = 2). The ninth patient required reconstruction of the subclavian artery sacrificed during excision of a malignant tumor. There were 5 femoral, 1 subclavian, 1 brachial, 1 posterior tibial, and 1 radial artery repairs. Direct arterial repair was accomplished in one patient with a brachial artery thrombus and another with a transected superficial femoral artery. Reversed saphenous vein grafts were used in the remaining patients. Iatrogenic dissection of the ipsilateral iliac artery necessitated use of a femofemoral bypass graft to achieve adequate inflow in one newborn. There were no operative deaths, no reexplorations, and normal perfusion was restored to all involved extremities. We conclude that microvascular technique allows early, successful arterial reconstruction and limb salvage in neonates and small children. PMID- 1941494 TI - Microbiologic characterization of ligature-induced peri-implantitis in the microswine model. AB - The purpose of this study was to evaluate the microbiologic changes associated with induction of peri-implantitis in the microswine. A split-mouth design was utilized. Three implants were placed in the edentulous mandibular bicuspid region of 2 microswine yielding 12 implants for evaluation. The experimental implant abutments were ligated with 4-0 silk suture material to induce peri-implantitis for a period of 45 days. The control implant abutments were not ligated. The control implants were scaled and cleaned at each time interval using plastic scalers. The attachment level (AL), probing depth (PD), gingival index (GI), and plaque index (PI) were measured at day 0 (baseline) and days 14 and 45. Microbiologic samples were taken from the "sulcus" with paper points at each interval and were dispersed in prereduced media; plated on selective and non selective media; and grown under aerobic, anaerobic, and capnophilic atmospheres. A greater AL, increased PD, and higher GI and PI scores were noted among the experimental implants. The controls remained essentially unchanged. Radiographs revealed that experimental implants showed an increased amount of bone loss when compared to control. Bone loss caused the implant threads to be exposed in the experimental implants. Microbiologic studies revealed that there was a shift from Gram-positive facultative organisms to Gram-negative obligate anaerobes, including black pigmented Bacteroides, in experimental implants. The microbiota of the control implants remained primarily Gram-positive facultative organisms. The microswine appears to be a suitable animal model for evaluation of osseointegrated implants. Importantly, under the experimental conditions reported, osseointegrated implants were susceptible to "periodontal" breakdown or peri-implantitis. PMID- 1941495 TI - The effects of a cetylpyridinium chloride prebrushing rinse as an adjunct to oral hygiene and gingival health. AB - A NUMBER OF MOUTHWASH PRODUCTS containing cetylpyridinium chloride (CPC) are available. Data for individual products are limited, although overall the antiseptic has been shown to reduce plaque. Results for gingivitis reductions by CPC have been equivocal. This study was an active/placebo parallel group design to evaluate the use of a CPC mouthrinse as an adjunct to oral hygiene when used before toothbrushing. Plaque and gingivitis scores were recorded at baseline and after 6 weeks, following twice daily use of the active or placebo prebrushing rinses. Plaque and gingivitis were significantly reduced at 6 weeks in both groups with no significant treatment differences between the active and placebo formulations. Whether the order of rinsing to toothbrushing influenced these findings cannot be determined. However, the results further question the adjunctive benefits of CPC rinses to gingival health. PMID- 1941496 TI - Sounding depth measurements: a method for evaluating various surgical techniques. AB - Fourteen patients undergoing periodontal treatment for moderate to severe adult type periodontitis were included in the study. Seven patients (a total of 210 sites) were treated with modified Widman flap surgery while the other 7 patients (the same number of sites) were treated with apically-positioned flap surgery. The 2 modalities were compared using sounding depth measurements before and immediately after surgery. The mean sounding depth decreased from 4.89 mm to 3.42 mm in the modified Widman flap group, compared to a drop from 4.77 mm to 2.46 mm in the apically-positioned flap group. Neither of these procedures resulted in the total eradication of all periodontal pockets. The final outcome of modified Widman flap surgery may, at times, result in zero sounding depth (placement of the flap at the crest of the bone); on the other hand, very often the flap was placed far supra-crestally in an intended apically-positioned flap procedure. This lack of consistency between intended and actual flap placement would suggest that studies which try to compare different treatment modalities using a flap approach should include sounding depth measurements immediately post-surgery. This is needed to assure that the intended procedure has actually been carried out. PMID- 1941497 TI - What alveolar crest level on a bite-wing radiograph represents bone loss? AB - In advanced periodontal disease alveolar bone crestal loss is readily apparent on radiographs. However, in incipient disease there is a lack of consensus regarding what constitutes crestal bone loss on a radiograph. To properly assess crestal bone loss radiographically requires an appropriate base of reference indicative of the absence of destructive periodontal disease. In this study the radiographic CEJ-crest distance as a measure of crest height was determined for sites at which clinical attachment measurements indicate no attachment loss. From these measurements it is concluded that no crestal bone loss is consistent with a range of radiographic CEJ-crest distance between 0.4 and 1.9 mm (95% confidence limits) as evidenced on bite-wings. PMID- 1941498 TI - Squamous cell carcinoma of the gingiva presenting as an endoperiodontic lesion. AB - An unusual case of gingival carcinoma, initially presenting as an endoperiodontic lesion without clinical evidence of malignancy, is presented. It is important to consider carcinoma of the gingiva in cases of an endoperiodontic lesion unresponsive to therapy, and to investigate further when bone resorption occurs around one tooth. Submission of all dental tissue removed during oral surgical procedures for pathologic analysis may be beneficial. PMID- 1941499 TI - Species difference of site-selective glucuronidation of morphine. AB - Species difference in glucuronidation of morphine was studied using mice, rats, guinea pigs and rabbits in vivo and in vitro. Morphine-3-glucuronide (M-3-G) and morphine-6-glucuronide (M-6-G) were determined by high-performance liquid chromatography. M-3-G was the major urinary metabolite of morphine in all these animal species. However, a remarkable species difference was observed in the urinary excretion of the M-6-G. Excretion ratios of the M-3-G to M-6-G were approximately 4:1 and 50:1 in guinea pigs and rabbits, respectively. The urinary excretion of M-6-G in mice and rats was too small to be determined. On the other hand, the ratios of uridine diphosphate-glucuronyltransferase (UDPGT) activities toward 3- and 6-hydroxyl groups of morphine in liver microsomes of mice, rats, guinea pigs and rabbits were approximately 300:1, 90:1, 4:1 and 40:1, respectively. Ratios of two morphine UDPGT activities in the liver microsomes of guinea pigs and rabbits, thus, reflected those of urinary excretion of morphine glucuronides. PMID- 1941500 TI - Tachyphylaxis to the inhibitory effect of manganese on potassium-induced contractions in the isolated vas deferens of the guinea pig. AB - In the isolated vas deferens of the guinea pig, the inhibitory effects of manganese (Mn2+) on the contractions induced by potassium (K+) were decreased when the contractions were induced repeatedly in the presence of Mn2+. This phenomenon appeared to be tachyphylaxis to the inhibitory effects of Mn2+. After the repetitive application of K+ with Mn2+, the phasic component of K(+)-induced contraction was restored, while the tonic component of this contraction and resting tone were augmented by the deprivation of extracellular Mn2+. When Mn2+ was applied during the tonic component of the K(+)-induced contraction, the phasic component of the next contraction induced by K+ in the absence of Mn2+ was slightly inhibited and the tonic component of the contraction was potentiated. When extracellular calcium concentration was increased, the inhibitory effect of Mn2+ on K(+)-induced contractions was reduced, while the tachyphylaxis to Mn2+ also appeared. Under this condition, the resting tone was markedly increased when the K(+)-induced contraction was repeated in the presence of Mn2+. In the calcium free medium containing Mn2+, although K+ caused slow and monophasic contractions, the magnitude of the contractions was much smaller than that of the contractions induced in the normal medium containing Mn2+. These results suggest that the tachyphylaxis was not produced by the decrement of the inhibitory effects of Mn2+ on the contractions but by the augmenting effects of intracellularly accumulated Mn2+ and that these augmenting effects of Mn2+ are not due to the direct action on the contractile proteins but due to the indirect action of Mn2+ which increased the availability of Ca2+. PMID- 1941501 TI - Effect of traditional Chinese herbal medicines on the pharmacokinetics of western drugs in SD rats of different ages. I. Aminophylline-Tin chuan Tang and aminophylline-Hsiao Ching Long Tang. AB - The effect of the traditional Chinese herbal medicines (Tin Chuan Tang and Hsiao Ching Long Tang) on the serum concentrations and pharmacokinetics of aminophylline was examined in three different ages of SD rats. Each traditional Chinese herbal medicine was orally preadministered to SD rats for one week and then aminophylline was administered intravenously. The serum concentrations and pharmacokinetic parameters of theophylline were estimated by a two-compartment open model. The liver isolated after the last blood sampling was homogenized and the activity of hepatic cytochrome p-450 was determined. Significant difference was found in some pharmacokinetic parameters of theophylline such as K10, t 1/2, Cl and Vd for three different ages of SD rats without pretreatment with Chinese herbal drugs (p less than 0.05). However, pretreatment with Tin Chuan Tang or Hsiao Ching Long Tang did not affect the pharmacokinetic parameters of theophylline in three different ages of SD rats (p greater than 0.05). We also found that there was no correlation between age and activity of cytochrome p-450 of SD rats (p greater than 0.05). The decline in some pharmacokinetic parameters of theophylline in the elderly rats perhaps might be attributed to the decrease in hepatic blood flow and liver volume. It is concluded that there was no drug interaction between theophylline and Tin Chuan Tang or Hsiao Ching Long Tang in the different ages of SD rats. PMID- 1941502 TI - Distribution of the mitogenic protein, sclerogen, in extracts from Sclerotinia sclerotiorum IFO 9395 assessed by using immunochemical analysis. AB - Sclerogen is a mitogenic protein isolated from the buffer extracts (3S) from sclerotia and shows significant mitogenic activity after heat denaturation accompanied with conformational changes. Experiments have been carried out to assess the distribution of sclerogen in several extracts from sclerotia and mycelia of this fungus by using the anti-serum against sclerogen. The anti-serum against the native- and heat denatured-sclerogen (anti-sclerogen-M and -MB serum, respectively) were prepared from Japanese white rabbits. These anti-sera showed different cross-reactivity to sclerogen-M and -MB from the results of immunoblotting after normal-polyacrylamide gel electrophoresis (normal-PAGE), suggesting that sclerogen-MB became to have different epitope(s) after heat denaturation of sclerogen-M. The result of immunoblotting after sodium dodecyl sulfate (SDS)-PAGE suggested that these anti-sera also recognized the random coil site(s) where the conformational specificity was not concerned, and that sclerogen (like substance(s] existed not only in mild extracts (e.g. phosphate buffer) but also in fractions extracted from mycelia of S. sclerotiorum IFO 9395. Taken together with the results of the mitogenic activity of the representative extracts from sclerotia, at least two kinds of the mitogenic substances would exist in sclerotia; one would be extracted by mild conditions, and the other would be difficult to extract and require drastic conditions such as hot water extraction. PMID- 1941503 TI - Pharmacokinetics of pirarubicin in pediatric patients. AB - The pharmacokinetics of pirarubicin and its active metabolite, doxorubicin, were studied after intravenous administration of pirarubicin (25-45 mg/m2) to ten pediatric patients. The concentration-time curves of pirarubicin in both blood and plasma showed representative biphasic patterns. Pirarubicin concentrations decreased rapidly from 0.5 to 2 h after administration and then decreased slowly until 24 h in all subjects. High concentrations of the metabolite, doxorubicin, were detected at 0.5 h after administration of pirarubicin which decreased gradually until 24 h. The area under the concentration-time curve from 0 to 24 h (AUC0-24) of pirarubicin and doxorubicin in blood were 3-4 times higher than those in plasma, suggesting that these drugs had a high affinity for blood cells. The AUC0-24 ratio of doxorubicin to pirarubicin in plasma was calculated to be 0.441. It might be indicated that not only pirarubicin but also doxorubicin are responsible for the therapeutic efficacy and the incidence of toxicity of pirarubicin. The pharmacokinetics of pirarubicin in pediatric patients was fundamentally similar to that of adults, but it was recognized that considerable interindividual variation in the disposition of pirarubicin and doxorubicin exists. PMID- 1941504 TI - Melatonin administration during pregnancy retards sexual maturation of female offspring in the rat. AB - The influence of pineal gland function and of melatonin during pregnancy upon sexual maturation of female offspring in rats was examined. The following groups of Wistar rats were studied: (A) control, (B) melatonin treated (250 micrograms/100 g.b.w. per day) throughout pregnancy, and (c) pinealectomized (pin x). Melatonin was injected subcutaneously 2 hr before lights off. All groups were housed in 12-hr L:12-hr D. The female offspring were observed until the onset of puberty, and blood samples were collected 5.5 hr after lights off under red light for melatonin and LH determinations by RIA. Ovary, pineal, and pituitary gland as well as body weights were recorded. The offspring of melatonin-treated rats showed later vaginal opening than did those of the other two groups (P less than 0.05 vs. control and P less than 0.01 vs. pin-x offspring), which was accompanied by a lower LH concentration, 0.42 + 0.05 ng LH/ml, showing statistically significant differences with the control levels [1.00 + 0.22 ng LH/ml (P less than 0.05)] and with the pin-x group [1.16 + 0.22 ng LH/ml (P less than 0.05)]. The percentage of rats in proestrus was higher in the offspring of pin-x rats (78.6%; P less than 0.01) compared to control offspring (30%) and offspring of melatonin-treated rats (11.8%). The concentrations of melatonin, 5.5 hr after darkness, were not significantly different among groups. No differences were observed in the body, ovarian, and pineal weights of the studied offspring. The pituitary weight was significantly lower (P less than 0.05) in the offspring of pin-x rats than in the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941505 TI - 5-Methoxypsoralen enhances plasma melatonin concentrations in the male rat: non noradrenergic-mediated stimulation and lack of effect in pinealectomized animals. AB - Previous studies have shown that 8-methoxypsoralen (8-MOP) is able to enhance melatonin secretion from rat pineal glands. The effect of another psoralen, 5 methoxypsoralen (5-MOP) on plasma melatonin concentrations alone or in combination with isoproterenol (Iso, 10 mg/kg BW, i.p.) or propranolol (Prop, 20 mg/kg BW, s.c.) was studied in the rat. An increase in plasma melatonin concentrations was observed 1 h after psoralen administration and lasted 8 h. The stimulatory effect of 5-MOP on circulating melatonin concentrations was dose dependent above 5-mg/kg, BW. 5-MOP also potentiated the Iso-induced rise in plasma melatonin levels. Furthermore, Prop did not block the effect of 5-MOP, indicating that the psoralen acts independently of the noradrenergic system controlling pineal melatonin synthesis. No increase in plasma melatonin levels was observed in pinealectomized (Px) animals after injection of 5-MOP (20 mg/kg BW) or 8-MOP (20 mg/kg BW). This demonstrates that the rise in plasma melatonin concentrations observed after treatment requires the presence of the pineal gland, and that neither 5-MOP nor 8-MOP stimulates melatonin release from other structures such as the retina or Harderian gland. PMID- 1941506 TI - Chronic administration of melatonin induces changes in porphyrins and in the histology of male and female hamster harderian gland: interrelation with the gonadal status. AB - In this paper, we have investigated the influence of melatonin on the histology and porphyrin content of the Syrian hamster Harderian glands. Daily afternoon injections of 25 micrograms of melatonin to female hamsters for 12 weeks resulted in the discontinuity of estrous cyclicity, a marked decrease in the Harderian gland intraluminal area occupied by porphyrins, and in a significant rise in the number of Type II cells. A similar decrease in porphyrins was observed after 8 weeks of ovariectomy. However, if the melatonin injections were given for only 8 weeks (without inducing gonadal atrophy), no changes were observed in the area occupied by intraluminal porphyrins, suggesting that the effects of melatonin in female Syrian hamsters might be associated with the subsequent gonadal atrophy. Castration of male hamsters induced a significant increase in porphyrins and a clear drop in the number of Type II cells. These changes were totally prevented when melatonin was administered daily from the day of castration. Our results suggest that melatonin, at least in male Syrian hamsters, plays a role in Harderian metabolism, acting directly on the Harderian secretory cells or indirectly through pituitary hormones. PMID- 1941507 TI - Low ambient temperature does not affect the pineal concentrations of either 5 methoxytryptamine or melatonin in golden hamsters kept under short photoperiod. AB - This work investigates the rhythmic synthesis of pineal 5-methoxytryptamine and related indoles in golden hamsters as a function of ambient temperature. 5 methoxytryptamine, 5-methoxytryptophol, 5-methoxyindole acetic acid, and melatonin were measured by high pressure liquid chromatography (HPLC) in the pineal gland of golden hamsters after inhibition of monoamine oxidase. In our experimental conditions, the pineal 5-methoxyindole concentrations of hamsters kept at 5 degrees C were similar to those observed at 20 degrees C. These results suggest that low temperature, which is known to accelerate the short photoperiod induced gonadal regression, acts at a level different to that of the pineal gland or affects another compound in the pineal gland. PMID- 1941508 TI - Gender stereotypes and the relationship between masculinity and femininity: a developmental analysis. AB - This study investigated developmental shifts in (a) the use of global gender stereotypes (base rates) and individuating gender-relevant information when making social judgments and (b) the perceived association between masculinity and femininity. Interviews/surveys of kindergartners, 3rd graders, 7th graders, 10th graders, and college students (N = 491) were conducted, in which Ss were presented with descriptions of boys or girls with stereotypical or counterstereotypical attributes and asked to judge other characteristics these boys or girls might have. The data indicated that (a) reliance on gender labels as judgment cues remains stable developmentally, (b) use of individuating information (particularly masculine individuating information) increases with age, and (c) the relationship between masculinity and femininity becomes increasingly negative with age, suggesting that gender may initially be viewed in dualistic terms but later as a unidimensional construct. PMID- 1941509 TI - Accuracy in the judgment of in-group and out-group variability. AB - The accuracy of in-group and out-group variability judgments was examined by comparing those judgments with the variability of self-ratings provided by random samples of group members. Following Park and Judd (1990), perceptions of both group dispersion and group stereotypicality were examined. Accuracy was examined both by within-subject sensitivity correlations and by simple discrepancies between perceived and actual variability estimates. In-group-out-group differences in sensitivity were shown, particularly for judgments of stereotypicality. These differences were related to differences in the degree to which out-group variability is underestimated relative to in-group variability (i.e., the out-group homogeneity effect). Out-group stereotypicality judgments were overestimated, supporting the view that out-group stereotypes are overgeneralizations. Whether dispersion judgments were over- or underestimated depended on their measurement. PMID- 1941510 TI - Automatic vigilance: the attention-grabbing power of negative social information. AB - One of the functions of automatic stimulus evaluation is to direct attention toward events that may have undesirable consequences for the perceiver's well being. To test whether attentional resources are automatically directed away from an attended task to undesirable stimuli, Ss named the colors in which desirable and undesirable traits (e.g., honest, sadistic) appeared. Across 3 experiments, color-naming latencies were consistently longer for undesirable traits but did not differ within the desirable and undesirable categories. In Experiment 2, Ss also showed more incidental learning for undesirable traits, as predicted by the automatic vigilance (but not a perceptual defense) hypothesis. In Experiment 3, a diagnosticity (or base-rate) explanation of the vigilance effect was ruled out. The implications for deliberate processing in person perception and stereotyping are discussed. PMID- 1941511 TI - Couples coping with a myocardial infarction: a contextual perspective on wives' distress. AB - Conventional models of stress and coping are highly individualistic and give little attention to circumstances and involvement with others. A more contextual perspective on wives of patients who had suffered myocardial infarctions was adopted in this study. Wives' distress was related to the character of the infarction, but initial contact with medical personnel and marital quality each had independent contributions. Other analyses related wives' distress to their and the patients' coping. Wives' protective buffering of patients had a positive relationship with their own distress, even though Smith & Coyne (1988) have shown it contributes to patients' self-efficacy. Results suggest the need to acknowledge the limitations on adaptation imposed by health and the health care system. Also, initial conditions set a trajectory for later adaptation and there may be tradeoffs between preserving one's own well-being and contributing to a partner's efficacy. PMID- 1941512 TI - Empathic joy and the empathy-altruism hypothesis. AB - Three experiments tested whether empathy evokes egoistic motivation to share vicariously in the victim's joy at improvement (the empathic-joy hypothesis) instead of altruistic motivation to increase the victim's welfare (the empathy altruism hypothesis). In Experiment 1, Ss induced to feel either low or high empathy for a young woman in need were given a chance to help her. Some believed that if they helped they would receive feedback about her improvement; others did not. In Experiments 2 and 3, Ss induced to feel either low or high empathy were given a choice of getting update information about a needy person's condition. Before choosing, they were told the likelihood of the person's condition having improved--and of their experiencing empathic joy--was 20%, was 50%, or was 80%. Results of none of the experiments patterned as predicted by the empathic-joy hypothesis; instead, results of each were consistent with the empathy-altruism hypothesis. PMID- 1941513 TI - Gender differences in negative affect and well-being: the case for emotional intensity. AB - Affect intensity (AI) may reconcile 2 seemingly paradoxical findings: Women report more negative affect than men but equal happiness as men. AI describes people's varying response intensity to identical emotional stimuli. A college sample of 66 women and 34 men was assessed on both positive and negative affect using 4 measurement methods: self-report, peer report, daily report, and memory performance. A principal-components analysis revealed an affect balance component and an AI component. Multimeasure affect balance and AI scores were created, and t tests were computed that showed women to be as happy as and more intense than men. Gender accounted for less than 1% of the variance in happiness but over 13% in AI. Thus, depression findings of more negative affect in women do not conflict with well-being findings of equal happiness across gender. Generally, women's more intense positive emotions balance their higher negative affect. PMID- 1941514 TI - Evidence of codependency in women with an alcoholic parent: helping out Mr. Wrong. AB - A conceptualization of codependency and its development, which is based largely on the writings of Karen Horney, is presented. It is proposed that having learned to obtain approval and self-esteem by conforming to the demands of an exploitive person, women with alcoholic parents will continue to seek opportunities to help such people. On the basis of this analysis, it was hypothesized that women with alcoholic parents would be more helpful to an experimenter portrayed as exploitive than to one portrayed as nurturant; women with nonalcoholic parents were expected to exhibit the opposite pattern. The results strongly supported the existence of codependent behavior in the women with alcoholic parents. The implication of these findings and directions for future research were briefly discussed. PMID- 1941515 TI - Social relationships, personality, and anxiety during a major stressful event. AB - Although it is commonly believed that social relationships buffer the effects of stress on mental health, these apparent buffering effects may be spurious reflections of personality or prior mental health. This possibility was investigated in a prospective study of a medical school entrance examination. Five weeks before the examination, Ss (N = 56) rated their personality (extraversion and neuroticism) and social relationships (number of social contacts and perceived support). They then rated their anxiety for 35 days surrounding the examination. Controlling for personality and prior anxiety, social contacts buffered against increases in anxiety, whereas perceived support did not. Further analyses revealed that discretionary social contacts were beneficial whereas obligatory contacts were not. PMID- 1941516 TI - The altruistic personality: in what contexts is it apparent? AB - Hypotheses concerning the specific contexts in which an altruistic personality might be most apparent were investigated. College students completed questionnaires tapping components of an altruistic personality, emotionality, and social desirability. At a 2nd session, the emotional evocativeness and ease of escape from the helping situation were experimentally manipulated. Ss were exposed to a distressed woman, completed state sympathy and personal distress indexes, and were given an opportunity to assist the woman. High scorers on dispositional altruism were expected to assist most when escape was easy, particularly when the distress cues were obvious. Altruistic and emotionally reactive persons were also expected to help most in a psychologically "weak" environment. Both predictions were supported. The relations between helping and the other predictors were also examined. PMID- 1941517 TI - Personality and socialization correlates of vicarious emotional responding. AB - The relations of personality and family characteristics to adults' negative vicarious emotional responses to sympathy and distress films were examined. Ss reported more sympathy and less personal distress and exhibited less skin conductance as well as heart rate deceleration when viewing a sympathy-evoking film. Dispositional emotional intensity and fantasy empathy were associated with greater self-reported emotional responding and higher skin conductance. Dispositional perspective taking and personal distress were positively and negatively correlated, respectively, with reported vicarious responding to the sympathy film when Ss were administered instructions to imagine the emotions of those in the films. Family cohesiveness was associated with reported sympathy and sadness in reaction to the sympathy film, whereas the expression of negative subordinate and positive emotional states in the home of origin was associated with women's reported responsivity. PMID- 1941518 TI - On the accuracy of ratings of personality by strangers. AB - Past studies in person perception have shown unexpectedly high correlations between targets' self-ratings of personality traits and ratings of those targets made by stranger judges. Possible reasons for the apparent accuracy of strangers' ratings are examined, including personality judgments that are based on (a) the perceived social desirability of targets, (b) known sex-linked base rates of behavior, and (c) the inevitable presence of valid personality cues in the typical stranger rating study. A computer simulation study is then described that illustrates that a relatively small number of nonrandom accurate judgments among many random judgments can produce substantial overall correlations between self ratings and stranger ratings. The data of the study provide some clarification of past empirical results of both stranger and acquaintance ratings of personality. PMID- 1941519 TI - Hassles, health, and personality. AB - College undergraduates (N = 211) responded to a "decontaminated" hassles scale plus measures of trait anxiety, reactivity, perceived stress, psychiatric symptomatology, and minor physical ailments. All but the anxiety and reactivity scales were time referenced to the past month. Major findings were as follows: (a) Hassles and trait anxiety both contributed positively to perceived stress, jointly accounting for 58% of the variance; (b) hassles and reactivity both had a significant positive impact on minor ailments, together explaining 23% of the variance; and (c) hassles and trait anxiety had a significant interactive effect on psychiatric symptomatology, which along with the nonsignificant marginal main effects accounted for 67% of the variance. The positive impact of hassles on psychiatric symptomatology increased as trait anxiety rose; likewise, the pathogenic effect of trait anxiety increased with greater exposure to hassles. PMID- 1941520 TI - A multidimensional analysis of internal health locus of control beliefs: separating the wheat from the chaff? AB - The current study examined the hypotheses that internal health locus of control comprises multiple dimensions and that these dimensions are differentially associated with physical health status. As expected, using covariance structure modeling of data derived from 181 medical outpatients, internal health locus of control was found to be multidimensional. Predicted dimensions included recognition that illness prevention is contingent on successful execution of potential health actions, recognition that illness management is contingent on successful execution of potential health actions, and self-mastery over health outcomes (i.e., the perceived capacity to achieve desired health outcomes). A 4th dimension (i.e., self-blame for negative health outcomes) also emerged. Moreover, as predicted, only perceptions of self-mastery were independently associated with indexes of physical health and well-being. PMID- 1941521 TI - The psychic costs of intense positive affect. AB - Recent research indicates that happiness, or affective well-being, is related primarily to the frequency, not to the intensity, of positive affect (PA). The question arises as to why intense positive affect (PI) is not a larger contributor to subjective well-being. Whether processes that yield PI also produce intense negative affect was examined. Studies 1 and 2 suggested that cognitive mechanisms that amplify or dampen affect can carry over from positive to negative events. Study 3 demonstrated that, because of judgment mechanisms, an extremely positive event can make other events less positive. Study 4 revealed that naturally occurring intensely positive experiences are often preceded by negative ones. Study 5 suggested that the more persons valence success at a task, the happier they will be if they succeed, but unhappier if they fail. The 5 studies reveal that intense positive experiences may sometimes have costs that counterbalance their desirable nature. PMID- 1941522 TI - Cognitive mediators of pain perception and tolerance. AB - A social learning model of pain perception and tolerance was evaluated. Responses to cold-pressor pain were examined in 4 groups of 20 Ss each. One group was given instruction in cognitive coping strategies, the 2nd was given a monetary incentive contingent on tolerance time, the 3rd was given both cognitive training and monetary reinforcement, and a no-treatment control group was given neither. Incentive and coping instructions significantly increased tolerance but did not alter pain perception. A path analysis indicated that pain tolerance was affected by self-efficacy, which in turn was predicted by pain expectancy and the provision of incentives. Incentive also had an impact on tolerance that was independent of self-efficacy. Pain perception was strongly affected by pain expectancy, but was unrelated to self-efficacy. PMID- 1941523 TI - AIDS and mucosal immunity: usefulness of the SIV macaque model of genital mucosal transmission. PMID- 1941524 TI - AIDS heterosexual predominance in the Dominican Republic. AB - AIDS surveillance data from the Dominican Republic are described for 1983-89. A positive serologic test for HIV was required, and standard clinical criteria were used for defining AIDS. There were 1,202 AIDS cases (820 men, 372 women, 10 of unknown gender) reported to the Ministry of Health, for a cumulative case rate of 17 per 100,000 persons. Rapid growth of the epidemic is noted, with 43% of the total cases reported in 1989. Heterosexual exposure accounts for 53% (593) of all cases, with a male-to-female ratio of 2.2:1, resembling a World Health Organization Pattern I/II country. Prevalence is highest in and surrounding the urbanized tourist areas of Santo Domingo and Puerto Plata and in districts with a high concentration of sugar plantation barracks, where laborers from Haiti and the Dominican Republic work and live. The distribution of AIDS cases is described by transmission exposure category, age, sex, year of diagnosis, and district. The National AIDS Surveillance Program can be improved by validation of exposure transmission categories through selected case investigation and by better reporting through training of health care providers. Surveillance data will assist in targeting future public health efforts to regions and persons at highest risk. PMID- 1941525 TI - The geographic and ethnic diversity of AIDS incidence trends in homosexual/bisexual men in the United States. AB - We examined geographic and racial/ethnic variation in acquired immune deficiency syndrome (AIDS) incidence in homosexual and bisexual men (i.e., men who report sex with men: MSWM) not using i.v. drugs in the United States. The AIDS incidence in these men has continued to increase in the United States. Incidence increased much less rapidly after 1986 in the three metropolitan statistical areas (MSAs) with the most cases, New York City, Los Angeles, and San Francisco, and may have reached a plateau in these areas. This change in incidence occurred in non Hispanic black and Hispanic MSWM as well as in non-Hispanic whites in these MSAs, but earlier in whites. There have been similar changes in incidence (but later in time) in all other MSAs with a population of at least 1,000,000 combined, with more tendency toward a plateau in whites than in non-whites. In contrast, incidence increased linearly through 1989 in MSAs with a population less than 1,000,000 and in rural areas, with no change in trend after 1986. Changes in human immunodeficiency virus (HIV) infection incidence before 1985, better therapy and medical care, and migration all contributed to these changes in incidence, as may have changes in reporting. Continued HIV seroconversions among MSWM show that efforts to prevent HIV infection must be continued in all areas of the United States. PMID- 1941527 TI - Production of a tac inhibitory activity by adherent cells of HIV-infected subjects at different clinical stages. AB - Studying the mechanisms of the impaired T-cell colony growth from HIV-infected subjects, we have demonstrated that depletion of adherent cells from some patients' peripheral blood mononuclear cells enhanced the plating efficiency of T colony-forming cells. We report here that media conditioned by patients' cells but not normal adherent cells could inhibit the expression of the interleukin-2 receptor alpha (IL-2R alpha) chain but not the IL-2R beta chain in a dose dependent manner. This inhibitory activity was produced by macrophage-monocyte cells since they displayed the My9+ My7+ OKM1+ phenotype and since adherent cell depletion by complement-mediated cytotoxicity with the My9 monoclonal antibody completely abrogated production of the inhibitory activity. A similar inhibitory activity, which could not be recognized by anti-p24 or anti-gp 120 monoclonal antibody or purified human anti-HIV immun]gobulin G in Western blot assays, could also be detected in culture supernatants of in vitro HIV-infected normal adherent and U937 leukemic cells. Production of IL-2R alpha chain inhibitory activity was associated with a decreased mitogen-induced expression of IL-2R alpha chain on patients' PBMC in 8 of 10 studied cases. Its production could be detected in 82, 58, and 91% of media conditioned by adherent cells from stage II, III, and IV patients, respectively. The amount of IL-2R alpha chain inhibitor released by patients' adherent cells increased during the deterioration of the patients' clinical status, and zidovudine treatment completely abrogated its production in all patients. These findings strongly suggest that production of IL-2R alpha chain inhibitory activity is involved in the pathophysiology of the impaired T cell responses during HIV infection and could be of clinical relevance during the patients' follow-up. PMID- 1941526 TI - Diagnosis and differentiation of HTLV-I and HTLV-II infection by enzyme immunoassays using synthetic peptides. AB - Synthetic peptides from the major envelope protein of HTLV-I (ENV-I, amino acid 177-213) and HTLV-II (ENV-II, amino acid 173-209) and a conserved region of the transmembrane protein (TM, amino acid 378-402) were used as antigens in microtiter plate enzyme immunoassays (EIA) to detect and discriminate antibodies to HTLV-I and II. The ENV-I and ENV-II peptide EIAs were able to correctly discriminate HTLV-I and II infections in 17 of 18 subjects whose infections were determined by a gene amplification method. Sera from 100 of 107 subjects with serologically confirmed infection with HTLV-I/II and 0 of 218 seronegative controls reacted with one or more of the peptides (sensitivity, 93.5%; specificity, 100%). Ninety-six of the 100 peptide positive sera reacted exclusively with either the ENV-I or the ENV-II peptide, thereby differentiating the two viral infections. The pattern of reactivity to the ENV peptides was distinct in different populations. Patients attending an Emergency Department, who had a history of drug abuse, and male inmate entering a correctional facility only had antibody reactivity to the ENV-II peptide. Subjects from Haiti and patients with HTLV-associated neurological disease only had antibody reactivity to the ENV-I peptide. Peptide-based enzyme immunoassays that distinguish antibodies to HTLV-I and HTLV-II will facilitate studies of the epidemiology of HTLV. PMID- 1941528 TI - Zidovudine-associated adverse reactions in a longitudinal study of asymptomatic HIV-1-infected homosexual males. AB - Chemotherapeutic regimens frequently interact with and may influence nutritional factors. To determine the possible effects of zidovudine (ZDV) treatment on nutrient status, this study examined and compared the nutritional, immunological, and hematological status of asymptomatic, CDC stage III, HIV-1-seropositive males (n = 15) provided with ZDV (500-1,200 mg/day) and 22 nontreated, CD4-matched HIV 1-seropositive subjects. Prior to ZDV administration, hematological and plasma nutrient levels were similar in both groups. Following ZDV treatment, drug treated subjects demonstrated alterations in hematological and nutritional parameters. A large proportion of the ZDV-treated participants exhibited decreased levels of zinc and copper along with a significant increase in red cell folate. The level of plasma zinc appeared to be particularly important in maintaining immune function in the ZDV-treated group. Whereas ZDV-treated subjects with adequate zinc levels displayed a significant increase in the response of peripheral blood lymphocytes to mitogens, this enhancement was not demonstrated in zinc-deficient, ZDV-treated participants or in untreated individuals whose lymphocyte response significantly declined over time, despite adeqaute zinc status. The findings of this study reveal a zidovudine-induced effect on nutritional parameters, indicating the importance of monitoring nutritional status with drug therapeutic regimens. PMID- 1941529 TI - Genetic comparison of human immunodeficiency virus (HIV-1) isolates by polymerase chain reaction. AB - Amplification of DNA by polymerase chain reaction (PCR) is influenced by the homology of oligonucleotide primers with the DNA template. We have developed a procedure, termed anchored PCR, whereby nucleotide sequence alterations in the template can be directly related to the quantity of amplified product. Genetic variation in the human immunodeficiency virus HIV-1 has been studied using anchored PCR. In four field isolates of the virus, the 3'LTR was compared both by PCR analysis of DNA from virus cultures and DNA sequencing. DNA templates that matched the primers varied less than threefold in PCR product yield, whereas significant 3' end primer-template mispairing decreased PCR product 10- to 100 fold. Using these guidelines for genetic variability manifested through PCR, 40 PCR primers encompassing the GAG, ENV, and 3' LTR segments of the genome were used to compare sequential HIV-1 isolates form six patients. Some primers were apparently located in genomic regions without significant interisolate variability, as they yielded equivalent amounts of amplified DNA from all the isolates. The quantity of amplified DNA obtained with other primers varied 10- to 100-fold among patients, but was consistent for sequential isolates from an individual patient. Two African HIV-1 isolates were readily distinguished from a panel of North American isolates by the same method. Systematic classification of HIV-1 genetic variants may be possible by anchored PCR. PMID- 1941531 TI - Sexual behavior in HIV-1-seropositive Zulu men and women in Durban, South Africa. PMID- 1941530 TI - Cytokine-activated human monocytes show differential cytotoxicity toward fresh and cultured Kaposi's sarcoma cells. AB - We have examined the ability of peripheral blood monocytes (PBMs) isolated from AIDS-related Kaposi's sarcoma (KS) patients or normal donors to kill (a) autologous KS tumor cells from skin biopsies of AIDS patients, (b) a tumorigenic cell line derived from a histologically verified AIDS-KS skin tumor, and (c) the WEHI-164 fibrosarcoma line. Unstimulated PBMs, and PBMs activated by IFNs, IL-2, or TNF-alpha, were tested for their ability to lyse 51Cr-labeled tumor targets. PBMs from both normal and KS patients, when activated by cytokines, showed enhanced cytolysis of both WEHI-164 and the KS cell line. PBMs from two of three AIDS patients lysed their autologous fresh KS tumor cells. These results indicate that PBMs from AIDS-KS patients can be induced by cytokines to elicit potent antitumor activity, including cytolysis of autologous KS tumor cells. PMID- 1941532 TI - On the conversion of thymidine phosphate bromohydrins to thymidine phosphates: a model reaction for the repair of oxidized nucleotides. AB - Bromohydrins (12, 13, and 14), which were oxidatively damaged products of thymidine nucleotides, were repaired by the action of sunlight (2700 lux) or heat via a radical mechanism to regenerate the original nucleotides (8,9, and 10). A significant effect of 3',5'-phosphate linkage on the repair reactions to natural type of thymidine nucleotide was proposed. PMID- 1941533 TI - [Effect of XKJ-001, a crude drug preparation, on body water distribution and water excretion in mice]. AB - The effect of XKJ-001, a crude drug preparation based on Seisho-ekki-to, was investigated on the hematocrit, plasma volume, extracellular and interstitial fluid volumes as well as water excretion in mice. Mice were housed in an animal room maintained at 34 degrees C for 3 d with water and food freely available. While the hematocrit, extracellular and interstitial fluid volumes increased, the plasma volume decreased. These results suggest that the distribution of body water in mice housed at high environmental temperature exhibit the state of water metabolism disorders (Suitai) described in Kampo medicine. After the administration of XKJ-001 (3 g/kg, once a day) for 5 d, mice were housed in an animal room maintained at 34 degrees C for 3 d. The administration of XKJ-001 was allowed to continue on the day 0, day 1 and day 2. XKJ-001 inhibited the increase in hematocrit and the changes in body water distribution of mice induced by high environmental temperature. An effect of XKJ-001 on water excretion in mice was investigated in comparison with hydrochlorothiazide (HTZ). Distilled water (D.W., 100 ml/kg) or bicarbonate saline (B.S., 100 ml/kg) was intraperitoneally injected immediately after the oral administration of XKJ-001 (1.5 g/kg) or HTZ (15 mg/kg). The water excretion was enhanced after 3 h for XKJ-001 and after 6 h for HTZ after the intraperitoneal injection of D.W. As for the intraperitoneal injection of BS, HTZ enhanced the water excretion, however, XKJ-001 exhibited no effect. These results suggest that XKJ-001 has activities on water maldistribution and facilitates the water excretion. PMID- 1941534 TI - [Studies on the anticomplementary activity of Jozann. Anticomplementary activity of steroid derivatives]. AB - Methanol extracts of 53 crude drugs were tested on the anticomplementary activity. Of these, 12 samples showed the potent activity. Of these 12 samples, the extract of Jozann (Dichrome Radix) was studied on the isolation and structural elucidation of the anticomplementary constituents. As active constituents, 3 beta-hydroxystigmast-5-en-7-one was isolated and its structure was confirmed by deriving this compound from beta-sitosterol. The activity of such steroid derivatives as stigmastane, cholestane, androstane and pregnane type steroids were further studied. Of these, several kinds of steroids showed the potent activity. From these experiments, the structure and activity relationship was discussed. PMID- 1941535 TI - [Saponins of anemarrhenae rhizoma]. AB - Three steroidal saponins 3, 4 and 5a were newly isolated from Anemarrhenae Rhizoma. Compounds 3 and 4 were identical with desgalactotigonin and F-gitonin, respectively. Compound 5a was established as (25S)-26-O-beta-D-glucopyranosyl-22 hydroxy-5 beta-furostane-3 beta,26-diol 3-O-beta-D-glucopyranosyl-(1----2)-O-beta D-galactopyranoside on the basis of chemical and spectroscopic evidence. PMID- 1941536 TI - [Phenolic constituents of licorice. IV. Correlation of phenolic constituents and licorice specimens from various sources, and inhibitory effects of licorice extracts on xanthine oxidase and monoamine oxidase]. AB - The roots and/or rhizomes of Glychyrrhiza uralensis, G. glabra and G. inflata, and commercial licorice specimens from various regions or countries were analyzed by high-performance liquid chromatography (HPLC), and classified into three types based on their phenolic constituents. i) Type A: The roots and rhizomes of G. uralensis, commercial licorice specimens from northwestern region of China (Seihoku-kanzo) and from northeastern region of China (Tohoku-kanzo) in Japanese markets, and also several licorice specimens from Chinese markets. They contain licopyranocoumarin (6), glycycoumarin (7) and/or licocoumarone (8), which were not found in G. glabra and G. inflata. ii) Type B: The root and rhizome of G. glabra, and the licorice specimens imported from the Soviet Union and Afghanistan. They contain glabridin (9) and glabrene (10), which were not found in the samples of the other two Glycyrrhiza species. A root sample of Glycyrrhiza species from Turkey also contains 9 and 10. iii) Type C: The root sample of G. inflata. They contain licochalcones A (11) and B (12), which were not found in the samples of the other two Glycyrrhiza species. Commercial licorice specimens obtained in Japan, which were imported from Sinkiang of China (Shinkyo-kanzo), and some licorice specimens obtained from Chinese markets, have also been found to contain 11 and 12. The phenolics 6-12, characteristic constituents of types A, B or C, were not found in a specimen of cortex-free licorice from a Japanese market (kawasari-kanzo). Extracts of some licorice specimens of types A and B, and all of the licorice specimens of type C inhibited 40-56% of the xanthine oxidase activity at the concentration of 30 micrograms/ml. Extracts of some licorice specimens of types A and B also showed inhibitory effects on monoamine oxidase (44-64% inhibition, at the concentration of 30 micrograms/ml), which were slightly weaker than that of harmane hydrochloride. PMID- 1941537 TI - [Studies on chemical protectors against radiation. XXXIV. Survival effects of aqueous extracts of various Chinese traditional medicines on radiation injury]. AB - In order to develop a nontoxic radioprotector, 60 kinds of Chinese traditional medicines were chosen, and their aqueous extracts tested for their survival effects against the lethal effect of X-irradiation in mice. Radiation factors used were as follows: soft X-rays, 2100R (5.418 x 10(-1) Ckg-1), 70 kVp, 10 mA, 10 mm acrylic filter, 70R (1.806 x 10(-2) Ckg-1)/min. Among 60 medicines tested by intraperitoneal injection immediately before the irradiation, 15 are shown to have the significant survival effect. These 15 effective medicines were also tested by intraperitoneal injection after the irradiation, and the survival effect was recognized in Keisi-syakuyaku-chimo-to, Keigai-rengyo-to, Simotu-to, Syakuyaku-kanzo-to and Hange-syasin-to. On the other hand, the survival effects of 25 medicines including the above-mentioned 15 medicines were investigated by the oral administration at various times before or after the irradiation. As the result of these studies, only Keigai-rengyo-to and Bukuryo-in are shown to have the significant survival effect when administered 2 h before the irradiation. PMID- 1941538 TI - Effects of ethanol on the pharmacokinetics of cephalexin and cefadroxil in the rat. AB - Data are presented on the effect of ethanol on the intestinal absorption and excretion in rats of two beta-lactam antibiotics, cephalexin (CFX) and cefadroxil (CFD). A recirculating perfusion technique within an antibiotic concentration range of 0.5 to 50 mM was used. Ethanol was administered either in an acute form into the intestine or in a chronic form as a 15% drinking solution for 2 months. The results are normalized in relation to the metabolic body weight, intestinal length, and osmotic conditions. Acute ethanol treatment decreases the antibiotic absorption; biliary excretion of CFD is increased, while urinary excretion of CFX is lowered. Chronic treatment shows slight negative effects on the absorption of CFX and CFD. Results are interpreted on the basis of the effect of ethanol on biological membranes. Enhanced urinary excretion after acute ethanol treatment, as well as differences between transport mechanisms, are invoked to explain these effects. PMID- 1941539 TI - Physical factors contributing to the partition coefficient and retention time of 2',3'-dideoxynucleoside analogues. AB - Acquired immunodeficiency syndrome (AIDS) is an immunosuppressive disease characterized by an immune impairment and a high susceptibility to unusual forms of certain neoplasms. Since the brain is an important site of the infection, it is necessary to explore new classes of drugs that have the ability to penetrate across the blood-brain barrier, and the potency to suppress viral replication within the central nervous system (CNS). Therefore, the ability to predicate the lipophilicity of the potent anti-AIDS drugs may provide useful information about the potential of the drugs to enter CNS. In this paper, the correlations of log P (octanol-buffer partition coefficient) and log tR (retention time in HPLC; Rt was used by Balzarini et al.) with some physical constants like log MW (molecular weight), hydrogen bond forming ability (HB) of the substituents, and the substituent group dipole moments (mu) are analyzed. Good correlations of log P and log tR with log MW, HB, and mu have been obtained. PMID- 1941540 TI - Increased tumor cisplatin levels in heated tumors in mice after administration of thermosensitive, large unilamellar vesicles encapsulating cisplatin. AB - Hyperthermia (HT)-dependent cisplatin (CDDP) release and tumor CDDP level increase after the administration of thermosensitive, large unilamellar vesicles (LUVs: LUV-1 and LUV-2) and a thermosensitive, small unilamellar vesicle (SUV: SUV-1) were examined in comparison with those following administration of a non thermosensitive LUV (LUV-3) and a CDDP solution (Sol) in tumor bearing mice. The LUV-1 and LUV-2 released CDDP at a faster rate than SUV-1 when incubated in saline at temperatures between 41 and 44 degrees C. The blood CDDP levels after liposome administration were higher than those after Sol administration. The systemic clearance of LUV-2 was slightly larger than those of the other liposomes. The tumor CDDP levels after thermosensitive liposome administration were increased in response to HT in comparison to LUV-3 or Sol. The increased ratio for LUV-1 was the largest. The ratio of the area under the tumor CDDP level versus time curve (AUC) for LUV-1 + HT to the AUC for Sol + HT was approximately 5. The results indicate that (1) the tumor-CDDP level increase after thermosensitive liposome administration is due to CDDP release from the liposome in the blood at or adjacent to the heated tumor, (2) the increase is highly dependent on the heat sensitivity and systemic stability of the liposome, and (3) LUV, such as LUV-1, exhibit higher heat sensitivity and larger, targeted drug delivery efficiency than SUV. PMID- 1941541 TI - Percutaneous penetration and skin retention of topically applied compounds: an in vitro-in vivo study. AB - Radiolabeled compounds with varying partition coefficients (paraoxon, benzoic acid, parathion, and DDT) were chosen to study the percutaneous penetration and extent of dermal retention in pig skin both in vitro and in vivo. Radiolabel distributions within the skin were determined from 1 min to 24 h after application in ethanol. The distribution of radioactivity in the skin during the first 4 h was comparable between in vitro and in vivo experiments. At 24 h, radioactive residues in the dermis were significantly higher in vitro than in vivo for DDT, the most lipophilic compound. Increasing air flow over the skin surface significantly increased evaporative loss for volatile compounds (benzoic acid, N,N-diethyl-m-toluamide, malathion, parathion, and DDT), significantly decreased the residues in the upper skin layer for N,N-diethyl-m-toluamide, malathion, parathion, and DDT, significantly decreased the dermal residue for malathion, and significantly decreased the penetration of N,N-diethyl-m toluamide, malathion, and parathion. On a percentage basis, increasing the dose of parathion and paraoxon from 4 to 1000 micrograms/cm2 resulted in significantly lower residues in the dermis. When applied to the dermis, the more hydrophilic benzoic acid and paraoxon better penetrated the dermis than the more hydrophobic parathion and DDT. An ethanol vehicle facilitated the penetration of parathion into the dermis and receptor fluid. These results indicate that the dermis interacted with the penetrant during both in vitro and in vivo percutaneous absorption. Factors such as partition coefficient and dose of the penetrant, air flow over the skin, and vehicle changed the distribution of penetrants in the skin and percutaneous penetration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941542 TI - Enhancing effect of pyrrolidone derivatives on transdermal penetration of 5 fluorouracil, triamcinolone acetonide, indomethacin, and flurbiprofen. AB - The enhancing effects of pyrrolidone derivatives on the transdermal penetration of 5-fluorouracil, triamcinolone acetonide, indomethacin, and flurbiprofen were studied by using an in vitro technique and full-thickness rat skin. The enhancers included 1-methyl (1), 1-hexyl (2), and 1-lauryl-2-pyrrolidone (3). Penetrants with various physicochemical properties were used. Flurbiprofen penetrated through skin rapidly after application alone. 5-Fluorouracil, triamcinolone acetonide, and indomethacin showed little penetration. Pyrrolidone derivatives enhanced the penetration of penetrants, especially the lipophilic compounds 2 and 3, which showed a great enhancing effect on the penetration of 5-fluorouracil and indomethacin. Pyrrolidone derivatives also enhanced the solubility of these penetrants in isopropyl myristate. Compounds 2 and 3 showed greater enhancing effects on the solubility and penetration of hydrophilic penetrants than those of lipophilic penetrants. These results suggest that the pyrrolidone derivatives enhance the flux of penetrants in skin by increasing the solubility of penetrants in the stratum corneum. Compounds 1 and 2 were detected in the receptor phase. All enhancers accumulated to a great extent in the skin. These derivatives also enhanced the skin retention of drug. It is concluded that these pyrrolidone derivatives are useful for transdermal drug delivery, although further studies are necessary before they could be used clinically. PMID- 1941543 TI - Administration of sulfhydryls to stimulate the healing of ischemia-induced acute gastric mucosal injury in the rat. AB - The sulfhydryl-containing agents DL-cysteine and DL-methionine-methyl sulfonium chloride (1-5%), administered orally by gavage for 4 days, stimulate the healing of acute ischemic injury of the rat gastric mucosa produced by 5 mg/kg of reserpine or 50 mg/kg of serotonin (5-hydroxytryptamine) injected once ip without influencing acid secretion (i.e., by cytoprotective mechanisms). PMID- 1941544 TI - Evidence of steric factors in the fungitoxic mechanisms of 8-quinolinol and its 5 and 7-halogenated analogues. AB - Antifungal studies were made of mixtures of minimal inhibitory concentrations (MICs) of 8-quinolinol and its 5- and 7-halo analogues against six fungi: Aspergillus niger, A. oryzae, Trichoderma viride, Myrothecium verrucaria, Mucor cirinelloides, and Trichophyton mentagrophytes. Mixtures of 8-quinolinol with 5- or 7-fluoro-8-quinolinol and of 5- and 7-fluoro-8-quinolinol showed additive activity, and their respective toxicities were reversed by L-cysteine. These results suggested a common mechanism of activity for the three toxicants. Potentiation of the fungitoxicity of mixtures of 8-quinolinol and its 5- and 7 chloro, bromo, and iodo analogues, as well as mixtures of 5- and 7-chloro, 5- and 7-bromo, and 5- and 7-iodo-8-quinolinols, along with the absence of protection of the fungi by L-cysteine from the toxicities of these compounds was observed. This suggested that the modes of action of these compounds were different from each other and from 8-quinolinol and the 5- and 7-fluoro analogues. The geometry of 8 quinolinol as influenced by substituents in the 5- and 7- positions of the molecule determines its site(s) of fungitoxicity. PMID- 1941545 TI - Enzymatic and nonenzymatic in vitro hydrolysis of 2-methyl-2-[2-(methoxy)phenoxy] 4H-1,3-benzodioxin-4-one and 2-methoxyphenyl O-acetylsalicylate. AB - This paper is concerned with the synthesis and physical properties as well as the enzymatic and nonenzymatic in vitro hydrolysis of the potential aspirin prodrug MR 693 (5) and the salicylic acid prodrug guacetisalum (6). The half-lives of both prodrugs and the amount of aspirin regenerated in each hydrolytic run for 5 have been estimated over a wide range of pH values. PMID- 1941546 TI - Antituberculosis agents. V: Alpha-[5-(5-nitro-2-furyl)-1,3,4-oxadiazol-2 ylthio]acethydrazide and related compounds. AB - alpha-[5-(5-Nitro-2-furyl)-1,3,4-oxadiazol-2-ylthio]aceth ydrazide, alpha-[5-(5 nitro-2-furyl)-1,3,4-oxadiazol-2-ylthio]acetamid e, delta-allyl-1-[( 5-(5-nitro-2 furyl)-1,3,4-oxadiazol-2-ylthio]acety) thiosemicarbazide, and other related compounds have been synthesised for testing against Mycobacterium tuberculosis. PMID- 1941547 TI - Preformulation studies of spironolactone: effect of pH, two buffer species, ionic strength, and temperature on stability. AB - Using a stability-indicating HPLC assay method, the effect of pH, two buffer species (citrate and phosphate), ionic strength, and temperature on the stability of spironolactone in 20% solution of ethyl alcohol in water has been studied. The optimum pH of stability appears to be approximately 4.5. On increasing the buffer concentration, both species hastened the decomposition of spironolactone. The ionic strength did not affect the stability of the drug. The energy of activation has been estimated to be approximately 78.8 kJ/mol at pH 4.3. The un-ionized spironolactone is subject to general acid-base catalysis. The Kh and Koh values at 40 degrees C have been estimated to be 1.63 and 2.8 x 10(5) day-1, respectively. The HPO4(-2) ion had approximately 10 times more catalytic effect than the H2PO4(-1) ion. This data will be used to develop a stable oral liquid dosage form of the drug. PMID- 1941548 TI - Synthesis and structural, conformational, and pharmacological study of some of esters derived from 3-phenethyl-3-azabicyclo[3.2.1]octan-8-beta-ol and the corresponding N-endo-methyl quaternary derivatives. AB - A series of 8-beta-acyloxy-3-phenethyl-3-azabicyclo[3.2.1]octane and its N-endo methiodides were synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of 8-beta-p-chlorobenzoyloxy-3-phenethyl-3 azabicyclo[3.2.1]octane methiodide (2c) was determined by X-ray diffraction. In CDCl3 solution, 1b-1e display the same preferred conformation. The cyclopentane and piperidine rings adopt an envelope conformation flattened at C-8 and a distorted chair conformation puckered at C-8 and flattened at N-3, respectively, with the N-substituent in the equatorial position with respect to the piperidine ring. In all cases, methylation takes place from the endo position. The ability of the title compounds to antagonize the acetylcholine-induced contraction of guinea pig ileum is also reported. An initial structure-activity relationship is proposed. PMID- 1941549 TI - Solid-state reaction between sulfadiazine and acetylsalicylic acid. AB - Kinetic data for the solid-state reaction of sulfadiazine and acetylsalicylic acid are presented. A compaction method was used to observe the influence of applied pressure, particle size, and temperature on the reaction rate. PMID- 1941551 TI - Isoxazoles. VII: Hydrolysis of 4-methyl-5-isoxazolylnaphthoquinone derivatives in aqueous solutions. AB - The kinetics for the degradation of 2-(4-methyl-5-isoxazolylamine)-N-(4-methyl-5 isoxazolyl)-1,4 -naphthoquinone-4- imine (1) in solution were investigated at 70 degrees C and at a constant ionic strength of 0.5 over a pH range of 1.75 to 12.85. The degradation rates were determined by absorption and second-derivative UV spectrometry. Two degradation products were identified in acidic and neutral pHs; they are 4-N-(4-methyl-5-isoxazolyl)-1,2-naphthoquinone (2) and 2-methyl cyanoacetamide (5), respectively. In alkaline pH, two degradation products, 2 hydroxy-N-(4-methyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (3) and 5-amino-4 methylisoxazole (4), were isolated. The pathway for degradation of 1 in acidic and neutral pH followed consecutive first-order kinetics since 2 undergoes hydrolysis giving 2-hydroxy-1,4-napthoquinone (6) and 2-methylcyanoacetamide (5). No appreciable buffer effect on the degradation of 1 and 2 was observed for any of the buffer species in this study. The pH-rate profiles exhibited specific acid and specific basic catalysis for 1 and specific acid catalysis for 2. The maximum stability for 1 and 2 occurred in the neutral pH region. PMID- 1941550 TI - Partial molal volumes and solubilities of physostigmine in isopropanol:isopropyl myristate solvents in relation to skin penetrability. AB - Partial molal volumes (Vi infinity) of physostigmine, ranging from 232.9 to 239.8 cm3.mol-1, and its mole fraction solubilities (Xi), ranging from 0.051 to 0.009, were determined at 25 degrees C in solutions of isopropanol (IPA), isopropyl myristate (IPM), and their mixtures. An inverse relation was found between Vi infinity and Xi. At solubility----0, Vi infinity----240.6 (by extrapolation). The experimentally derived liquid molal volume in the standard state, Vi degrees (231.1), of physostigmine was lower than its lowest Vi infinity (value 232.9) in the series tested. Virtual cohesion parameters (lambda i) and excess free energies (delta EGi) of physostigmine in the various solutions were estimated from the partial molal volumes, assuming regular solution behavior. For each solution, the free energy (-RT In Xi) of the drug was estimated from its solubility. An increase in the virtual cohesion parameter and a decrease in the excess free energy and the free energy was found with an increase in volume fraction of IPA in the mixed solvent. The increase in lambda i over the invariant cohesion parameter, delta i (10.2), reflects a compensation effect needed to maintain the geometric mean assumption of Regular Solution Theory. Deviation from the theoretically expected linearity between -RT In Xi and delta EGi of physostigmine is ascribed to the existence of solvated molecules distinct from unsolvated molecules of physostigmine. The highest permeability coefficient of the delivery of physostigmine through excised human skin from IPA:IPM mixtures was seen from the mixture exhibiting the highest solvation effect, giving additional evidence that physostigmine penetrates through the skin, possibly in combination with IPA. PMID- 1941552 TI - Fourier transform infrared spectroscopic studies of human serum albumin microcapsules prepared by interfacial cross-linking with terephthaloylchloride: influence of polycondensation pH on spectra and relation with microcapsule morphology and size. AB - Fourier transform infrared (FT-IR) spectroscopic studies were performed on microcapsules prepared through interfacial cross-linking of human serum albumin (HSA) with terephthaloylchloride at various pH values (5.9 to 11). Correlations were established with morphology and size of microcapsules. Increasing polycondensation pH resulted notably in a progressive increase of peaks at 1795 and 1724 cm-1, assigned to anhydride and ester; respectively, in a decrease of the carboxylate-assigned 1394 cm-1 peak, and in alterations of the 1340-1080-cm-1 region. These spectral changes were most pronounced from pH 9 and were shown to correspond to smaller-sized microcapsules (mean size decreased from 30-40 microns to less than 15 microns) with rough surfaces. Further soaking of highly cross linked microcapsules in a pH 7.5 buffer resulted in the disappearance of the 1795 cm-1 peak, with a concurrent increase of the 1394 cm-1 peak and a decrease of the 1724 cm-1 peak. These changes, attributed to complete breaking of anhydride and partial hydrolysis of esters, were accompanied by an unwrinkling of the microcapsule membrane, then made smooth, and a significant increase in size. Treating microcapsules with hydroxylamine under alkaline conditions allowed complete reversal of the spectral alterations assigned to anhydride and ester formation. A comparable (slightly higher) increase in size was observed with microcapsules which exhibited smooth surfaces and a low density. PMID- 1941554 TI - Regarding dose-independent pharmacokinetic parameters in nonlinear pharmacokinetics. PMID- 1941553 TI - Partitioning of solutes in different solvent systems: the contribution of hydrogen-bonding capacity and polarity. AB - Published partition coefficient values of 121 solutes in five solvent systems (1 octanol-water, n-heptane-water, chloroform-water, diethyl ether-water, and n butyl acetate-water) were correlated with solute properties, namely intrinsic molecular volume (indicator of cavity formation) and the solvatochromic parameters pi* (dipolarity/polarizability), beta (H-bond acceptor basicity), and alpha (H-bond donor acidity). While the cavity term and the H-bond accepting capacity played a comparable role in all solvent systems, the H-bond donor acidity was significant only in the alkane-water and chloroform-water systems. Comparison of the regression coefficients of pi*, beta, and alpha demonstrated the important role that water content at saturation in the organic solvents plays in the partitioning of solutes. Analysis of the differences between 1-octanol water and n-heptane-water partition coefficients (delta log Poct-hep) and between 1-octanol-water and chloroform-water partition coefficients (delta log Poct-chf) showed that these values mainly quantitate the capacity of solute to donate hydrogen bonds. In contrast, the differences between 1-octanol-water and diethyl ether-water or n-butylacetate-water partition coefficients, (delta log Poct-dee and delta log Poct-ba, respectively) contain no structural information. PMID- 1941555 TI - Biological activity of insulin in microemulsion in mice. PMID- 1941556 TI - Effects of vasoactive drugs on transdermal lidocaine iontophoresis. AB - The effect of co-administration of vasoactive drugs on the transdermal iontophoretic delivery of lidocaine.HCI was studied in in vitro cells, in the isolated perfused porcine skin flap (IPPSF), and in vivo in pigs. Iontophoresis of lidocaine in vitro across human and porcine skin were similar, supporting the use of porcine skin as an appropriate animal model. Co-iontophoresis of the vasodilator tolazoline marginally decreased lidocaine flux in vitro, but significantly increased it in the IPPSF and in vivo. In contrast, norepinephrine decreased lidocaine flux in the IPPSF. Vasomodulation also changed the shape of the venous efflux profile in the IPPSF as evidenced by changes in fractional absorption index, as well as the AUC. These studies demonstrate that co iontophoresis of vasoactive compounds may significantly alter the transdermal delivery of lidocaine and that use of vitro animal model systems which possess a functional microcirculation are essential to study this process if reliable extrapolation to the in vivo setting is desired. PMID- 1941557 TI - Stochastic interpretation of linear pharmacokinetics: a linear system analysis approach. AB - Linear drug disposition is most generally defined in terms of the superposition principle. This principle is explained on the molecular level by probability principles involving stochastic, independent kinetic behavior of drug molecules. A stochastic modeling approach is presented that is more general than pharmacokinetic models typically employed in stochastic approaches. First-order microscopic transfer rate constants (Kij) are not employed or assumed in the analysis. The approach is a linear system analysis approach that makes use of the simplest possible kinetic structure that enables a differentiation of the drug disposition into elimination and distribution components. This is done by applying stochastic principles in the context of the disposition decomposition analysis (DDA). The DDA approach in its linear form is a generalization of linear pharmacokinetic systems that assume a homogeneous sampling space. Disposition kinetics is partitioned into two kinetic spaces, a homogeneous sampling space, and a heterogeneous peripheral kinetic space. A structure differentiation beyond this is difficult to justify in common situations when only the parent drug is determined from a single iv sampling site. A stochastic independent molecule (SIM) model is formulated in the structure context of DDA. The model is employed to identify core relationships by isolating elementary stochastic building blocks of the disposition kinetics and absorption kinetics. It is shown how the stochastic building blocks of the SIM-DDA model are related to various mean time parameters. Residence probability functions and drug delivery probability functions provided by the approach appear useful for extending kinetic bioavailability concepts into a purely stochastic realm. The emphasis on transit time concepts enables a kinetic differentiation and a more intrinsic characterization than possible by the use of common residence time principles. Relationships are presented that link stochastic and kinetic elements. Formulas are presented for the practical calculations of the mean time parameters and stochastic functions presented. Practical examples are given of the concepts presented using data from several drugs. PMID- 1941558 TI - Relationship between skin fluorescence and blood flow in normal and in chronically ischemic subjects dosed with fluorescein. AB - To elucidate parameters diagnostic of chronic ischemia, the fluorescence of skin on the foot, leg, arm, and forehead of six chronically ischemic patients and six normal subjects injected with fluorescein was measured serially using a surface measurement fluorometer (dermofluorometer). Simultaneously collected plasma samples were assayed spectrofluorometrically for unmetabolized fluorescein. The time courses of plasma fluorescein content and dermofluorometer readings were jointly analyzed by combining a standard pharmacokinetic model, a model predicting skin site from plasma concentrations of fluorescein, and a model predicting the dermofluorometer response to those skin concentrations. Fluorescein plasma clearance (0.22 +/- 0.06 versus 0.46 +/- 0.20 L/h/kg) in ischemic patients was only half, and half-life was double (2.4 +/- 1.0 versus 1.3 +/- 0.3 h) those in normal subjects, with volume of distribution (Vdss = 0.46 L/kg) being similar. Despite the ischemia diagnosis for all patients involving claudication of the lower extremities, patients could be distinguished statistically from normal subjects on the basis of fluorescence readings taken on the arm, but not those using the foot or leg. The rate constant describing flux of fluorescein from the arm skin site in patients was only half that in normal subjects, and the peak reading on the arm occurred at 42 +/- 14 min after fluorescein injection in patients, but at only 15 +/- 6 min in normal subjects. Lack of discrimination between subject groups via leg and foot readings may be due to several physiologic and/or experimental factors, including the need to take skin surface readings much earlier than previously recognized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941559 TI - Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics and pharmacodynamics of furosemide in rats. AB - The effects of pretreatment with the enzyme inducers phenobarbital (PB) and 3 methylcholanthrene (3-MC) on the pharmacokinetic and pharmacodynamic parameters of furosemide were examined in rats. The nonrenal clearance (4.58 versus 6.18 mL/min/kg) increased significantly in PB-treated rats. This suggested that the nonrenal metabolism of furosemide increased by pretreatment with PB. This relationship was supported by the results of a tissue homogenate study; the amounts of furosemide remaining per gram of tissue after 30 min of incubation of 50 micrograms of furosemide with the 9000 x g supernatant fraction of liver, stomach, and kidney tissue homogenates decreased significantly in PB-treated rats. The contents of hepatic cytochrome P-450 (1.29 versus 2.15 nmol/mg protein) and the weights of liver and stomach increased significantly in PB-treated rats, suggesting that the metabolizing enzymes for furosemide are induced by pretreatment with PB. The 8-h urine output per 100 g of body weight increased significantly in PB-treated rats; however, the 8-h urinary excretion of furosemide per 100 g of body weight (797 versus 635 micrograms) decreased significantly in PB-treated rats. Alterations in the urine output might be due to the hormonal alterations in the concentration-effect relationship for furosemide in PB-treated rats. In 3-MC-treated rats, pharmacokinetic and pharmacodynamic parameters of furosemide were not significantly different, indicating that the metabolizing enzymes for furosemide were not induced by pretreatment with 3-MC. However, the contents of hepatic cytochrome P-450 and the weights of liver and stomach increased significantly. PMID- 1941560 TI - In vitro release and intestinal absorption of physostigmine salicylate from submicron emulsions. AB - The in vitro release of physostigmine salicylate (PS) from a submicron emulsion and an aqueous solution was studied using the dialysis bag method. These formulations were then perfused to various locations along the rat small intestine (proximal, mid, and distal jejunum), and two lengths (10 and 55 cm). The disappearance of PS from the luminal compartment and its appearance in the blood compartment was monitored. In the in vitro drug release from emulsion experiments, a biphasic appearance of PS in the sink solution was observed, suggesting a possible sustained release from the emulsion. However, absorption data from perfusion studies did not correlate with this in vitro observation. No significant difference was found in absorption from emulsion versus solution in the mid jejunum where PS absorption was maximal. The difference between the two liquid formulations was observed only in those intestinal segments where the absorption was relatively low [absorption rate values of 4.6 +/- 0.86 and 9.98 +/ 2.04 (log%/min) x 10(-3) in the proximal and distal parts of the small intestine, respectively, as compared with 14.0 +/- 1.2-14.8 +/- 1.1 (log%/min) x 10(-3) in the mid jejunum]. In the distal part of the rat small intestine, PS was absorbed significantly better from solution than from the submicron emulsion. Cholinesterase activity in blood samples collected after intestinal perfusion with emulsion or solution revealed lower enzyme activity following emulsion administration. PMID- 1941561 TI - Dose-dependent pharmacokinetics of enprofylline and its renal handling in rats. AB - The effect of dosage on the pharmacokinetics of the potent bronchodilator enprofylline (3-propylxanthine; PX) and its renal handling were investigated in rats. Enprofylline (PX) was administered iv in dosages of 2.5, 10, 20, and 40 mg/kg, and PX concentration in plasma and urine was determined by HPLC. The pharmacokinetic parameters were estimated by model-independent methods. The disappearance of PX from plasma was delayed as dosage was increased. The corresponding pharmacokinetic parameters also showed dose dependency; increases in the volume of distribution (Vd) and mean residence time (MRT) and a decrease in total body clearance (CLT) were observed as dosage was increased from 2.5 to 40 mg/kg. Approximately 80% of the dose, however, was excreted in urine as unchanged PX. Plasma protein binding studies of PX showed concentration dependency and allowed determination of binding parameters, with an apparent dissociation constant (Kd) of 162.50 microM and a binding capacity (nP) of 565.23 microM. Some pharmacokinetic parameters for unbound PX calculated by total plasma concentration and binding parameters also showed dose-dependent characteristics. However, no significant change in Vd for unbound PX was observed among administered doses, indicating that the distribution of PX into the body tissues is not changed by an increase in dosage. Renal clearance of unbound PX significantly increased as plasma concentration decreased. The maximum transport capacity (Vmax) and the Michaelis-Menten constant (Km) for tubular secretion were 60.53 micrograms/min and 2.27 micrograms/mL, respectively. The aim of the present study is to demonstrate that both saturable tubular secretion and concentration dependent protein binding are responsible for the dose-dependent pharmacokinetics of PX in rats. PMID- 1941562 TI - Naftidrofuryl protects the rat against chronic gastric ulceration. AB - Intraperitoneal reserpine (5 mg/kg every day for 5 days) produced solitary chronic ulceration of the rat stomach after 2 weeks. Gavage with 1 mL/day of 1% naftidrofuryl oxalate for 2 weeks protected 30% of rats against ulceration and this protection extended to 70% of cases with a 2% solution. Similar gavage with a 5% solution protected all rats against ulceration without significantly influencing the basal H+ output (14.8 +/- 0.6 versus 15.4 +/- 0.5 mumol, mean +/- SEM, n = 10); that is, cytoprotection was achieved. PMID- 1941563 TI - A novel method for differentiating dextran sulfate from related sulfated polysaccharides. AB - A method is described for unequivocal identification of dextran sulfate, based on combined chemical desulfation and dextranase enzymolysis of dextran sulfate moieties to isomaltose, a specific indicator of dextran-type precursors. The method was developed using high-resolution (300 MHz) 1H NMR spectroscopy for assurance of the molecular transformations, identification, and estimation of the hydrolysis products. Overall conversion of approximately 80% of highly sulfated and moderately sulfated dextran sulfates was realized. Both 2-D 1H and 13C NMR spectra of a dextran sulfate (MW 500,000) clarified the extent of sulfation (75%) at C-4 and confirmed that sulfation at positions C-2 and C-3 was virtually complete. Estimation of the hydrolysis products (isomaltose, major; alpha-D glucose, minor) is not restricted to 1H NMR now that the desulfation-enzymolysis methodology has been established; rather, it can be performed using HPLC or GLC (with derivatization). PMID- 1941564 TI - Synthesis, stereochemical analysis, and neuromuscular blocking activity of oximino ether derivatives of progesterone. AB - This study consists of the synthesis, separation, and stereochemical analysis of oximino ethers, followed by a preliminary pharmacological evaluation for neuromuscular blockade. Synthesis of the compounds began with the double oximation of progesterone, which yielded EE and ZE dioximes as major products. Both stereoisomers were separated and purified by chromatography followed by crystallization. The diether of each dioxime was prepared by O-alkylation with 2 dimethylaminoethyl chloride hydrochloride, using a mixture of potassium tert butoxide and sodium hydride as base. The diethers were separated from the monoethers by vacuum chromatography. Configurational assignments of all compounds were based on 1HNMR and 13CNMR spectroscopy. Quaternization with methyl bromide yielded the salts which were purified via fractional crystallization. A preliminary pharmacological evaluation was conducted by using mice on a treadmill apparatus. Structure-activity relationships are discussed on the basis of similarities to succinylcholine. PMID- 1941565 TI - Coffee contains cholinomimetic compound distinct from caffeine. I: Purification and chromatographic analysis. AB - Both regular and decaffeinated coffees were found to have cholinomimetic actions when tested in urethane-anesthetized rats. These actions were distinct from those of caffeine and reversible by atropine. The bioactive fraction was purified from alcoholic extracts of instant decaffeinated coffee by liquid column chromatography and preparative TLC. The purified compound showed similar pharmacological actions as the starting material. Chromatographic behavior was further characterized by analytical TLC and HPLC. Chromatographic analyses of extracts of green coffee beans and roasted ground coffees showed that the cardioactive compound was only present in roasted coffees. Similar analyses of other commonly consumed beverages, including teas and cocoa, showed that this compound was not present in beverages besides coffee. PMID- 1941566 TI - Timolol release from matrices of monoesters of poly(vinyl methyl ether-maleic anhydride): effects of polymer molecular weight and a basic additive. AB - Alkyl monoesters of poly(vinyl methyl ether-maleic anhydride) (PVM-MA) are acidic bioerodible polymers that have been used in cosmetics and tablet film coatings. They may be suitable for topical controlled-release applications since the polymeric backbone is not cleaved to smaller fragments that could be absorbed into the systemic circulation. The dissolution of these polymers depends on the length of the alkyl ester chain of the polymer and on the pH on the polymer surface. We studied the effect of the molecular weight of the polymer on in vitro release of timolol from matrices of n-propyl, n-butyl, and n-hexyl monoesters of PVM-MA. The effect of a basic additive, disodium phosphate, on timolol release from the polymers was also evaluated. The rate of timolol release decreased with increasing length of the alkyl side chain in the polymer. Drug release from the n propyl and n-butyl monoesters followed zero-order release kinetics, but that from the n-hexyl monoester followed square root-of-time release kinetics. The molecular weight of the polymer did not affect drug release from the matrices without disodium phosphate. With the basic additive, the rate of timolol release increased with increasing molecular weight from the matrices of n-propyl and n butyl monoesters of PVM-MA, but had only a very small effect on drug release from the n-hexyl monoester. Release of timolol from the n-propyl and n-butyl monoesters was controlled by polymer dissolution and, thus, it was affected by the basic additive in the matrix. Diffusion-controlled drug release from the n hexyl ester was not affected by disodium phosphate. PMID- 1941567 TI - Stability of aspartame in water: organic solvent mixtures with different dielectric constants. AB - In order to examine the influence of solvent composition on the stability of aspartame (N-alpha-L-aspartyl-L-phenylalanine-1-methyl ester) in solution (5 mg/mL), the degradation of aspartame was carried out in water:methanol, water:ethanol, and water:glycerine mixtures with dielectric constant values of 45, 55, and 65, respectively. The rate of disappearance of aspartame was measured by a sensitive HPLC assay. The degradation rate of aspartame increased as the dielectric constant of the solvent mixture decreased in all three solvents systems. For example, at 60 degrees C, the degradation rate constants were 4.1, 5.9, and 8.4 x 10(-3) h-1 at dielectric constant of 65, 55, and 45, respectively. From these results, it can be concluded that the stability of aspartame in aqueous solutions cannot be enhanced by the replacement of water by solvents of lower dielectric constant. PMID- 1941568 TI - Solid state properties of an oral iron chelator, 1,2-dimethyl-3-hydroxy-4 pyridone, and its acetic acid solvate. I: Physicochemical characterization, intrinsic dissolution rate, and solution thermodynamics. AB - 1,2-Dimethyl-3-hydroxy-4-pyridone (1), a crystalline oral iron chelator, forms an acetic acid solvate (2) on recrystallization from acetic acid and carbon tetrachloride. Compound 2 forms compact prisms, and 1 forms needles from water (mp 274 degrees C). The X-ray powder diffraction patterns of 1 and 2 differ, indicating distinct solid phases. Compound 2 has an extra DSC endotherm at 82 degrees C that is accompanied by a weight loss of 29% in TGA, corresponding to the desolvation of a 1:1 acetic acid solvate. Comparison of the solid-state 13C NMR of 1 and 2 revealed two additional peaks for 2 at 20.3 and 175.6 ppm, characteristic of -CH3 and -COOH, respectively, of acetic acid. The integrated intensities confirmed the 1:1 stoichiometry between 1 and acetic acid. However, 2 underwent desolvation in air at 25 degrees C as suggested by a change in its appearance to opaque crystals and as confirmed by X-ray powder diffraction, DSC, and TGA. Desolvation of 2 at 25 degrees C was a zero-order process with a rate constant of 6.9 mumol.h-1. X-ray powder diffraction showed that crystals or compacted discs of 1 are converted to 2 in contact with glacial acetic acid (A), whereas crystals or discs of 2 are converted to 1 in contact with water. The intrinsic dissolution rate (J) and the apparent solubility (Cs) of compacted discs of 1 and 2 were measured in water at 25 degrees C, and the following relations were determined: J(2)/J(1) = 1.39 and Cs(2)/Cs(1) = 1.70.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941569 TI - Syntheses of psoralen analogues and evaluation of their inhibition of epidermal growth factor binding. AB - An exchange hydrogenation reaction on trioxsalen yields two isomeric dihydro analogues for which a combined HPLC-supercritical fluid chromatography method supplies purified materials. These reduced compounds and a related benzodipyranone are biologically active and inhibit the binding of epidermal growth factor on HeLa cells to an even greater extent than trioxsalen. This observation suggests a non-DNA target may play a role in the overall effects of psoralens on cells. PMID- 1941570 TI - Spectrophotometric determination of hydralazine with 2-hydroxy-1-naphthaldehyde in pharmaceuticals. AB - A new extraction-spectrophotometric method for the determination of hydralazine, based on its reaction with 2-hydroxy-1-naphthaldehyde at 25 degrees C, is described. The calibration curve was linear between 0.4 and 6 mg/mL of hydralazine. The molar absorbtivity of the product at 408 nm is 40,900 L.mol-1.cm 1. The method described was applied to the analysis of hydralazine in pharmaceutical preparations containing reserpine, hydrochlorothiazide, bendrofluorthiazine, propranolol, and other substances. The agreement with the U.S.P. XXI method was satisfactory for tablets and injections, but not for pellets. PMID- 1941571 TI - Effects of nitrendipine on cocaine-induced toxicity evaluated in primary myocardial cell cultures. AB - Currently, there is no uniform treatment for abnormal cardiac events precipitated by cocaine use. However, clinical strategies include use of calcium channel antagonists for cardiovascular emergencies. In experimental situations using rats, simultaneous administration of nitrendipine (NIT) with cocaine to the whole animal (1.46 x 10(-3) mg/kg/min of NIT; 2 mg/kg/min of cocaine) and isolated retrograde perfused hearts (Langendorff; 1 x 10(-7) M NIT; 1 x 10(-7) to 1 x 10( 4) M cocaine) normalized cocaine-induced abnormalities in heart rhythm and provided protection from acute cocaine-induced morphological lesions. Using similar concentrations of NIT and cocaine, the purpose of this study was to evaluate the direct cardiac cellular effects of NIT on cocaine-induced alterations in beating activity, morphology, and lactate dehydrogenase (LDH) release in a controlled in vitro system of primary myocardial cell cultures. Cultures were established from hearts of 3-5-day-old Sprague-Dawley rats. After the cells had been maintained in culture for 4 days, evaluation of drug effects were made with exposure to 1 x 10(-3) and 1 x 10(-5) M cocaine alone and combinations of these two concentrations of cocaine with simultaneous exposure to 1 x 10(-7) M NIT for 1 to 24 h. Those cells exposed to 1 x 10(-5) M cocaine alone maintained some beating activity after 1, 4, and 24 h. Beating activity was significantly depressed after treatment with 1 x 10(-3) M cocaine alone and with both combinations of cocaine and NIT. Morphological integrity was maintained in all treatment groups for 1 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941573 TI - Evidence that dogs do not model enantioselective pharmacokinetics of dl methylphenidate in humans. PMID- 1941572 TI - Synthesis and anticonvulsant activity of some new 3,6-disubstituted-2-[2-oxo-2-(4 pyridyl)ethyl]-4(3H)-pyrimidinones. PMID- 1941574 TI - Comparative pharmacokinetics of unbound disopyramide enantiomers following oral administration of racemic disopyramide in humans. PMID- 1941575 TI - Bioavailability of a poorly water-soluble drug from tablet and solid dispersion in humans. PMID- 1941577 TI - Structural biomechanics of the foot bones. AB - The structure of the tarsal and metatarsal bones reflects the functional demands placed on them. Their shape and the arrangement of compact and trabecular bone within them help them resist the normal forces of everyday life. When the limits of their strength are exceeded, failure can occur. PMID- 1941576 TI - Commentary on "Influence of food on the bioavailability of verapamil". PMID- 1941578 TI - Torsional development of the lower extremity. Implications for in-toe and out-toe treatment. AB - The authors provide a comprehensive review of the nature, origins, and natural history of torsion of the lower extremity. Norms for children and adults are discussed, along with implications for treatment. PMID- 1941579 TI - The clinical anatomy of tendons. AB - The main features of tendon anatomy are described. From the clinical viewpoint, the most significant are those relating to connective tissue layers surrounding tendons: the paratenon and the synovial (tendon) sheath, and the sources and sites of blood supply. These aspects of tendon anatomy are interactive in the healing process, which requires continuation of blood supply into the tendon while avoiding functionally inhibiting adhesions in the connective tissue. Surgical methods of tendon repair and techniques for achieving successful postoperative results are reviewed. PMID- 1941580 TI - Clinical aspects of bursae and tendon sheaths of the foot. AB - The evaluation and treatment of bursitis in the foot is a complex problem for the clinician. There is no one standard approach or set treatment for the patient who presents with pain suspected of being secondary to bursal involvement, primarily because there are myriad conditions and anatomical sites involved. Compounding this problem is the wide variation in the presence of these structures from patient to patient. Therefore, each distinct pathologic situation must be examined, diagnosed, and treated, based on its individual anatomical and etiologic factors. In the interest of completeness, the special anatomy of bursae and their specific pathologic conditions are reviewed. PMID- 1941581 TI - Deep fascia of the foot. Anatomical and clinical considerations. AB - The deep fascia of the foot lies beneath the subcutaneous tissue and surrounds the intrinsic foot muscles. Depending on its location, the composition of the deep fascia varies. In some areas it is thin, while in other areas it is greatly thickened to form retinacula and the plantar aponeurosis. Selected clinical considerations that relate to the deep fascia of the foot are described. These include the following: plantar fasciitis, infection, compartment syndrome, calcaneal fracture, and neuroma. PMID- 1941582 TI - Skin and superficial fascia of the foot. AB - The authors provide a brief review of the structure of the skin in general and the specializations of the plantar skin and superficial fascia. This review is intended to provide a basis from which the reader can interpret any relevant data in other papers on anatomy and to direct the reader to a variety of more detailed references. PMID- 1941584 TI - Is there a limit to the validity of peer review? PMID- 1941583 TI - An unusual intermetatarsal coalition. AB - Synostoses commonly occur in the midfoot and rearfoot. However, metatarsal synostosis is a less common phenomenon. Several etiologies have been described. The authors present a case of a fourth-fifth intermetatarsal bar, which does not fit into one of the established categories, along with the surgical technique used in its correction. PMID- 1941586 TI - Suture adjustment for postkeratoplasty astigmatism. AB - Excessive corneal astigmatism following penetrating keratoplasty is a frequent problem. A technique that adjusts a single running 10-0 nylon suture after keratoplasty was used in this series of patients. The procedure requires a keratometer, slitlamp, topical anesthesia, and tying forceps. In 52 eyes, with an average of 10.0 diopters of keratometric astigmatism, we adjusted the suture to flatten the steep corneal axis. We were able to reduce astigmatism an average of 7.2 diopters and this remained stable three months post wound revision. PMID- 1941585 TI - Postoperative fluctuations of tissue plasminogen activator (t-PA) in aqueous humor of pseudophakes. AB - We studied the quantitative fluctuations of tissue plasminogen activator (t-PA) activity and antigen in aqueous humor before and after extracapsular cataract extraction and poly(methyl methacrylate) posterior chamber lens implantation. The t-PA activity level was measured by solid phase bioimmunoassay using monoclonal antibody against an epitope apart from the active site of t-PA, and the antigen by ELISA. In our patients the mean preoperative level of t-PA activity was 0.0664 +/- 0.0472 IU/ml (mean +/- SD) and of the antigen, 0.175 +/- 0.024 ng/ml. The t PA activity level in aqueous humor was markedly decreased on the first postoperative day (0.0042 +/- 0.0037 IU/ml), recovered on the second day (0.0403 +/- 0.0251 IU/ml), and then progressively decreased from the fourth to the seventh days. The t-PA antigen level in aqueous humor increased on the first (0.366 +/- 0.108 ng/ml) and second (0.403 +/- 0.251 ng/ml) postoperative days and gradually decreased from the fourth to seventh days. Under the intracameral condition of the fibrinolytic system, various factors, e.g., serious inflammation or events affecting the balance of coagulation and fibrinolysis, may induce the decrease or depletion of t-PA activity, followed by the pupillary fibrin membrane formation. We suggest that fluctuations of t-PA activity in aqueous humor may affect fibrinous membrane formation over the IOL surface. PMID- 1941587 TI - Organic tissue glue in the closure of cataract incisions in rabbit eyes. AB - We performed 7 mm scleral pocket cataract incisions in both eyes of ten rabbits. One eye of each rabbit was closed with one interrupted 10-0 nylon suture and organic tissue glue (Tisseel) and the other was closed with a conventional shoelace running 10-0 nylon suture. The eyes were examined clinically and histopathologically at various postoperative intervals. No difference in wound integrity was found between the two closures, but slightly more inflammation occurred in the eyes closed with glue than in those closed with sutures alone. Organic tissue glue may become an alternative method to suture closure of scleral pocket cataract incisions. PMID- 1941588 TI - Microendoscopic ocular surgery: a new intraoperative, diagnostic and therapeutic strategy. Part I: Endoscopic equipment/methodology applied to cataract surgery with intraocular lens implantation. AB - During posterior chamber implantation, endoscopy is the only direct method that allows objective observation of the retroiridal space. We use it to define the parameters of the posterior chamber intraocular lens (isolation, inertia, centering). An oval endoscopic probe is preferred and the multivision system allows observation of the endoscopic images under the operative microscope eyepiece. Beside "blind" posterior chamber implantation, a "controlled" endoscopic posterior implantation can be defined. PMID- 1941589 TI - Microendoscopic ocular surgery: a new intraoperative, diagnostic and therapeutic strategy. Part II: Preliminary results from the study of glaucomatous eyes. AB - Endoscopy allows intraoperative examination of the retroiridal space; this procedure has been used during the combined surgery of trabeculectomy, extracapsular extraction, and posterior chamber intraocular lens implantation. Information obtained by preoperative gonioscopic examination of the iridocorneal angle is presented with information obtained by intraoperative endoscopic examination of the iridocorneal and ciliary angles. Our initial endoscopic findings are impressive and include morphological analysis of ciliary processes, variations in their appearance, degree of opening of the iridociliary angle, and study of ciliary capillaries. PMID- 1941590 TI - Personal results with the 3M diffractive multifocal intraocular lens. AB - The results of implanting 269 3M multifocal intraocular lenses are analyzed and compared with those of monofocal lenses. Visual acuity results were excellent. In the best case group, 98% of eyes obtained a distance visual acuity of 20/40 or better and 96% of best cases obtained a functional reading capacity without supplementary reading correction. On contrast sensitivity testing, eyes with the 3M multifocal intraocular lens performed slightly less than eyes with a monofocal lens using the Regan low contrast charts and the Vistech charts for near vision. PMID- 1941591 TI - Optical performance of an aspheric multifocal intraocular lens. AB - A five zone, centrosymmetric, multifocal intraocular lens has been developed using a design analysis approach which assumes that the optical image strength (intensity) achieved by an optical zone is linearly proportional to its aperture. The advantages of including an aspheric zone are discussed, and the optical performance of this IOL is characterized interferometrically. Optical resolution data have been obtained according to the ANSI procedure, using standard Air Force targets. These experimental data are compared with theoretical models of optical performance of diffraction-limited circular, annular, and compound circular annular lenses. PMID- 1941592 TI - Tilt and decentration of the implanted posterior chamber intraocular lens. AB - Management of surgically induced astigmatism is an important problem for surgeons implanting intraocular lenses. Besides corneal astigmatism, the fixation status of the intraocular lens (IOL) may contribute to total astigmatism. This study was undertaken to evaluate the effect of tilt and decentration of the implanted posterior chamber IOL on the total astigmatism. The tilting angle of the IOL was measured by a method using the 3rd and 4th Purkinje images, and the grade of the decentration was obtained photogrammetrically. The average tilt angle was 7.53 +/ 3.03 degrees (SD). The average decentration was 0.68 +/- 0.33 mm (SD) from the corneal center. Based on these data, the astigmatic error induced by the tilt or decentration of the implanted IOL was calculated as within 0.4 diopter. These data suggest that the fixation status of the IOL implanted in the bag does not cause a serious astigmatic error. PMID- 1941593 TI - Further studies on ultraviolet-absorbing hydrogels for intraocular lenses: relationship between concentration of a polymerizable benzophenone, absorption, and extractability. AB - A tendency to reduce the use of benzophenone absorbers is currently evident in the manufacture of the UV-absorbing IOLs, mainly because the cutoff wavelengths are inferior to those provided by benzotriazoles. In principle, by incorporating large amounts of benzophenones it may be possible to achieve high cutoff wavelengths. A covalently bondable benzophenone UV absorber, Cyasorb UV-2098, was incorporated in poly(2-hydroxyethyl methacrylate) (PHEMA) in increasing concentrations, and certain associated phenomena were investigated. At 4% w/w absorber content, the nonhydrated polymers turned partially opaque. In water swollen hydrogels, opacification occurred at a lower absorber content (2% w/w). By using extraction techniques and gas chromatography, we also found that up to 8% w/w of the absorber remained unpolymerized and could leach out from any material containing less than 5% w/w absorber. In samples with higher initial content of absorber, the amount of unreacted, leachable absorber was significantly higher (25% to 30%). Based on this study model (hydrogel/Cyasorb UV 2098), we concluded that benzophenone absorbers cannot provide cutoff wavelengths higher than those provided by benzotriazoles. PMID- 1941594 TI - Neodymium:YAG laser damage to UV-absorbing poly(methyl methacrylate) and UV absorbing MMA-HEMA-EGDMA polymer intraocular lens materials. AB - MemoryLenses and UV-poly(methyl methacrylate) intraocular lenses, which served as controls, were individually exposed to twenty 5 mJ shots of the Nd:YAG laser focused onto the posterior surface while placed in a sterile holder containing 5 ml of saline. The MemoryLens is a new foldable intraocular lens (IOL) manufactured from a polymer consisting of methyl methacrylate (MMA), 2 hydroxyethyl methacrylate (HEMA), and ethylene glycol dimethyacrylate (EGDMA) with a UV absorber. Damage to the lenses was assessed by scanning electron microscopy. Cytotoxicity tests designed to detect potentially toxic substances released during laser damage were conducted with the saline solution by incubating it with mouse fibroblasts. Additional tests of the saline solution were conducted by high performance liquid chromatography and spectrophotometry. Damage induced by the Nd:YAG laser to the UV-poly(methyl methacrylate) IOLs was similar to that reported by other authors. Damage to the MemoryLens appeared less severe and showed no radial stress cracking. Cytotoxicity tests were negative for both types of IOLs. High performance liquid chromatography tests were negative for residual monomers (MMA, HEMA, EGDMA) and spectrophotometry did not reveal residual UV absorber. PMID- 1941595 TI - New cryoprotectant for cryorefractive surgery. AB - Cryorefractive surgeries, keratomileusis, keratophakia, and epikeratophakia cause destruction of keratocytes, which may result in postoperative corneal haze. We examined the effects of two cryoprotectants on keratocyte survival following freeze injury. We compared the ability of CPTES and the standard cryoprotectant KM-26 to prevent keratocyte death by altering the length of time corneal tissue was exposed to the cryoprotectant. When corneal stroma was immersed in CPTES for five minutes prior to freezing, 66.5% of the keratocytes survived; when tissue was immersed in KM-26 for the same length of time, 27.5% survived (P less than .01). Immersion for one to 30 minutes in CPTES prior to freezing produced keratocyte viabilities that were 40% to 80% of those of fresh, unfrozen tissue; immersion in KM-26 produced keratocyte viabilities of 20% to 60%. We compared the ability of these cryoprotectants to reduce corneal haze following freeze injury using our rabbit model of lamellar keratoplasty. The postoperative data were comparable to those in the cell culture experiments. Based on our findings in rabbit corneas, a cryoprotective medium such as CPTES may promote cell survival and thereby speed recovery from cryorefractive procedures in humans. PMID- 1941596 TI - Protective effects of Healon and Occucoat against air bubble endothelial damage during ultrasonic agitation of the anterior chamber. AB - An important aspect of any new viscoelastic substance is the corneal endothelial protection. We compared the protective effects of sodium hyaluronate (Healon) and hydroxypropylmethylcellulose (Occucoat) by introducing a controlled volume of air bubbles into the anterior chamber of human eye bank eyes during ultrasonic agitation of the anterior chamber. Eight eyes received Healon and 11 eyes received Occucoat. Damage to endothelial cells in the central cornea was quantified by vital staining. Endothelial damage averaged 4.5% in eyes in which no viscoelastic was used (positive control); damage was 0.4% in eyes in which a viscoelastic was injected but no air bubbles were introduced (negative control). We found that endothelial damage averaged 4.25% in specimens that received air plus Healon and 1.4% in specimens that received air plus Occucoat. Occucoat appeared to have somewhat better protective effects than Healon against air bubble damage to the corneal endothelium during ultrasonic agitation of the anterior chamber. PMID- 1941597 TI - Spontaneous breaks in proteinaceous membranes on intraocular lenses. AB - Spontaneous breaks in proteinaceous membranes on the surface of intraocular lenses are demonstrated with pathological and clinical methods. These breaks appear to be the result of traction and can be a horseshoe or radial-traction type. The breaks are repaired by the natural process of protein film deposition on the newly exposed area. PMID- 1941598 TI - Long-term endothelial cell loss and breakdown of the blood-aqueous barrier in cataract surgery. AB - Progressive endothelial cell loss and endothelial cell loss induced at the time of surgery occurs in all eyes with rigid anterior chamber intraocular lenses (IOLs). Eyes with surgical tuck or late ovaling of the pupil following surgery have greater yearly rates of cell loss than eyes that have no complications. This progressive loss may be related to chronic uveitis from iris chafing by the implant or to direct mechanical damage to the corneal endothelium. We have demonstrated that fluorophotometry shows chronic damage to the blood-aqueous barrier in all eyes with rigid anterior chamber IOLs, but this does not correlate with the degree of endothelial cell loss. Our results suggest there is damage to the blood-aqueous barrier and to the corneal endothelium, but the damage to the latter influences progressive endothelial cell loss. PMID- 1941599 TI - Continuous circular capsulorhexis and nucleus delivery in planned extracapsular cataract extraction. AB - A technique for nucleus delivery through a continuous circular capsulorhexis in planned extracapsular cataract extraction is presented. The concept of hydro- and viscoexpression of the nucleus is explained, and a strongly bent cannula specially designed for the procedure is introduced. PMID- 1941600 TI - Nucleus-splitting phacoemulsification technique. AB - A technique for phacoemulsification that can be used with or without capsulorhexis and that allows surgery to be performed at the 12 o'clock position is described. Following central sculpting, the nucleus is tipped superiorly to the level of the iris plane with a second instrument and the phacoemulsification tip. The hard nucleus is split from the soft nucleus, leaving two bowl-shaped pieces. The nucleus is rotated and the hard nucleus is removed with a phacoemulsification tip while the softer nucleus or epinucleus is ignored. Once the hard nucleus has been removed, the epinucleus follows easily into the phacoemulsification tip. The technique is advantageous for beginning phacoemulsification surgeons and offers an alternative for very hard nuclei with small pupils. PMID- 1941601 TI - Sulcus fixation of posterior chamber lenses by transscleral sutures. AB - Sulcus fixation of posterior chamber lenses by transscleral sutures was performed in 23 cases. We used new techniques to be sure that the sulcus was pierced accurately and the suture was placed in the posterior chamber instead of the ruptured capsule. This paper describes these techniques and the clinical results of 23 cases. PMID- 1941602 TI - Study of laser damage to injection-molded diffractive intraocular lenses. AB - A study of the probability of damage induced in two implant quality injection molded diffractive intraocular lenses by a commercial Q-switched Nd:YAG laser is presented. The damage thresholds of the diffractive intraocular lenses (0.10 mJ at 10% probability, 0.24 mJ at 50% probability, and 0.90 mJ at 99% probability) did not differ significantly from those of other poly(methyl methacrylate) lenses manufactured with the same technology. These low values (compared to those of other lens types) suggest that care should be taken during laser capsulotomy in eyes implanted with refractive lenses, with special attention given to power losses at the target site due to diffraction effects. PMID- 1941603 TI - Consultation section. A 67-year-old healthy female had uncomplicated extracapsular cataract extraction with implantation of iridocapsular metallic two looped lenses in both eyes 15 years ago. PMID- 1941604 TI - Experimental evaluation of a phakic anterior chamber implant in a primate model. PMID- 1941606 TI - Not norepinephrine but its oxidation products bind specifically to plasma proteins. AB - Specific binding (up to 50%) of catecholamines to the plasma proteins albumin, transthyretin and alpha-1 acid glycoprotein has been reported repeatedly, but data are conflicting. In binding studies of tritiated norepinephrine (NE) to human serum albumin, we found specific binding to be an artifact, due to the presence of one or more oxidation products of NE which are rapidly formed at pH greater than 6.5. In the presence of large amounts of antioxidants NE is stable, and no specific binding occurs. The decrease in binding of tritiated NE with increasing amounts of nontritiated NE, previously thought to represent displacement, is actually the result of the inherent greater stability of NE at higher concentrations. A similar decrease in binding, this time representing real displacement, was obtained with increasing amounts of oxidation products, obtained by treating NE first with sodium hydroxide. Results with transthyretin, alpha-1 acid glycoprotein and with plasma were in full agreement with these conclusions. These observations emphasize the necessity for careful investigation of the purity and stability of the labeled ligand, not only in binding assays with catecholamines, but in binding assays in general. Our findings may also have bearings on the currently hotly pursued topic of catecholamine release in in vivo and in vitro experiments. PMID- 1941605 TI - Analysis of serotonergic mechanisms underlying benzamide-induced gastroprokinesis. AB - Serotonin (5-HT) receptors in the myenteric plexus mediate contractility in vitro and may regulate gastric emptying in vivo. This report examines the pharmacology of three benzamides, ML-1035 (4-amino-5-chloro-2-[2-(methylsulfinyl)-ethoxy]-N-[2 (diethylamino)ethyl]-benzamide hydrochloride), metoclopramide and cisapride, in studies which address the serotonergic mechanisms underlying benzamide-induced gastroprokinesis. All three compounds had high affinity at the 5-HT3 receptor as they displaced the 5-HT3 antagonist [3H]GR65630 from cortical membranes (Ki = 156, 232 and 1711 nM for ML-1035, metoclopramide and cisapride, respectively) and blocked the 5-HT-induced Bezold-Jarisch reflex, although cisapride was much less active in this experiment. Receptor selectivity was also compared at 5-HT1, 5 HT2, and dopamine D2 receptors in which no displacement was observed that was common to all agents. All benzamides elicited a 5-HT4-like agonist response as they enhanced field-stimulated neurogenic contractions in ileum (EC50 = 1.4, 1.6 and 0.013 microM for ML-1035, metoclopramide and cisapride, respectively). ICS 205-930, a proposed 5-HT4 antagonist, competitively antagonized this response for ML-1035 (Kb = 1.6 microM) whereas atropine blocked the twitch response and any additional responses to ML-1035. In vivo, ML-1035 and metoclopramide increased gastric emptying (IC50 = 0.87 and 3.09 mg/kg i.p., respectively). Thus, the benzamides activate a 5-HT4 receptor in the ileum which increases cholinergic contractions and may be one mechanism by which these agents increase gastric emptying. PMID- 1941607 TI - Electrophysiological actions of BRB-I-28 in canine myocardial tissues. AB - To obtain a better understanding of the possible electrophysiological bases of the antiarrhythmic actions of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate (BRB-I-28), microelectrode recordings of myocardial electrical activity were obtained in canine Purkinje and ventricular tissue, and in isolated canine ventricular myocytes. BRB-I-28 (1.0 and 3.2 mg/l) reduced Vmax, action potential amplitude, overshoot potential and conduction velocity in Purkinje tissues without altering action potential duration or spontaneous automaticity. Vmax and conduction velocity were reduced only at paced cycle lengths of 500 msec or less. BRB-I-28 (3.2 and 10 mg/l) also reduced Vmax, action potential amplitude and overshoot potential in subendocardial and epicardial ventricular muscle, with Vmax reduced only at cycle lengths of 500 msec or less. Recovery half-times for Vmax estimated in canine subendocardium were 330 +/- 28 and 336 +/- 25 msec at BRB-I-28 concentrations of 3.2 and 10 mg/l, respectively. In epicardium, conduction velocity longitudinal to fiber orientation was depressed more than conduction velocity transverse to fiber orientation, despite similar changes in Vmax. In both epicardial and subendocardial ventricular muscle, a reduction in Vmax is observed in the absence of alterations in action potential duration. Experiments using myocytes isolated from canine epicardial tissue demonstrated similar rate-dependent changes in Vmax as ventricular epicardium. The data demonstrate a rate-dependent depression of Vmax by BRB-I-28 in canine ventricular tissues. The depression of conduction occurs only at rapid paced rates and occurs in the absence of changes in Purkinje cell automaticity or action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941608 TI - Release of platelet activating factor by the isolated kidney is not linked to the production of prostaglandins. AB - In many isolated tissues, including glomerular mesangial cells and endothelial cells, the synthesis of platelet activating factor (PAF) occurs by remodeling the phospholipids so that the production of PAF results in the release of arachidonic acid with subsequent production of cyclooxygenase or lipoxygenase products. In some tissues, including the renal medulla, another pathway for PAF biosynthesis (the de novo pathway) has been found in which the production of PAF is not linked to the production of arachidonic acid products. We tested the hypothesis that the remodeling pathway was active in the release of PAF into renal venous effluent of the isolated kidney. Isolated rat kidneys perfused at constant flow with albumin containing buffer were stimulated to produce prostaglandin by an infusion of angiotensin II or bradykinin. Some kidneys were also challenged with the calcium ionophore A23187. Perfusate was collected for bioassay of PAF and radioimmunoassay of prostaglandin (PG) E2; urine was collected for PAF bioassay. Angiotensin II (10(-9) to 10(-8) M) increased renal vascular resistance, and bradykinin (10(-8) to 10(-7) M) and A23187 (3 x 10(-6) M) reduced renal vascular resistance. PGE2 production was increased significantly by bradykinin and angiotensin II but not by A23187. Only A23187 increased the release of PAF into the perfusate. Urine PAF was not changed by any of the stimuli. These data indicate that the release of PGE2 by the isolated, perfused rat kidney can be dissociated from the release of PAF. The findings support the suggestion that PAF released by the kidney into the renal venous effluent is not produced by remodeling the lipids that are the source of renally released prostaglandins. PMID- 1941609 TI - Binding of [3H]AF-DX 384 to cloned and native muscarinic receptors. AB - The binding selectivity of [3H]AF-DX 384 [(+-)-5,11-dihydro-11- ([(2-(2 [(dipropylamino)methyl]-1- piperidinyl)ethyl)amino]carbonyl)-H-pyrido(2,3 b)(1,4)benzodiazepine-6-o ne] was evaluated with cloned human muscarinic receptors (M1-M4) in Chinese hamster ovary (CHO-K1) cell lines as well as in rat heart and brain. There were uniform classes of sites for the radioligand in the M2-rich tissues, heart (Kd = 2.3 nM) and brainstem (Kd = 2.4 nM). However, [3H]AF DX 384 bound to all four cloned receptor subtypes. Using kinetic methods, the calculated Kd values were M2 (1 nm) greater than M4 (2.2 nM) greater than M3 (15 nM) greater than M1 (55 nM). Scatchard analysis with the CHO cells confirmed the high affinity of this radioligand for the M2 (1.8 nM) and M4 (2.5 nM) receptors. To evaluate the potential for selectively binding to M2 and M4 receptors in cortex and striatum, low concentrations (0.5-0.8 nM) of the radioligand were used and a two-site competition model was used to derive the binding constants for pirenzepine and AF-DX 116 [(+-)-11-2((-((diethylamino) methyl)-1 piperidinyl)acetyl)-5,11-dihydro-6H- pyrido(2,3-b)(1,4)-benzodiazepine-6-one] and to compare them with values obtained with cloned M2 and M4 receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941610 TI - Facilitated transport of cefodizime into the rat central nervous system. AB - The disposition of [14C]cefodizime, a nonmetabolizable analog of cefotaxime, in the central nervous system was studied in control and benzylpenicillin-infused rats using in vivo experimental techniques. After i.v. bolus administration of [14C]cefodizime, a concentration gradient was established from the brain extracellular fluid (ECF) to the cerebrospinal fluid (CSF) (i.e., drug penetration into the CSF after i.v. administration can be accounted for by permeation across the cerebral capillaries and diffusion through the brain ECF and across the ependymal surface into the CSF). Kinetic analysis indicated that the cerebrovascular transfer coefficient for plasma unbound [14C]cefodizime in control rats equaled 5.2 x 10(-5) ml/sec/g brain, a value comparable to that for mannitol. In rats which received an i.v. infusion of benzylpenicillin, the cerebrovascular transfer coefficient for [14C]cefodizime was reduced to approximately 1/15th of the control value, resulting in a reduced central nervous system (brain ECF and CSF)/plasma unbound concentration ratio for this drug. After i.c.v. administration, the efflux of [14C]cefodizime from CSF was comparable to that of [3H]mannitol with a small probenecid-sensitive component and was not affected by treatment with benzylpenicillin. These results indicate that the unidirectional influx of [14C]cefodizime into brain ECF and then into the CSF is facilitated by a mechanism shared with other beta-lactam antibiotics. PMID- 1941611 TI - Protection by butyrylcholinesterase against organophosphorus poisoning in nonhuman primates. AB - Butyrylcholinesterase (BuChE) was examined as an in vivo exogenous scavenger for highly toxic organophosphorus (OP) poisons. Protection studies with equine BuChE were carried out in rhesus monkeys trained to perform a Serial Probe Recognition task. The pharmacokinetics of equine BuChE administered i.v. in rhesus monkeys revealed an elimination T1/2 of approximately 620 hr. Animals given 503 nmol of BuChE i.v. and then challenged with 220 to 260 nmol of soman (two LD50; a lethal dose in untreated animals) all survived with no clinical signs of OP poisoning. Serial Probe Recognition performance was depressed after enzyme administration and at 1 hr postsoman. However, all monkeys performed the task at base-line levels at 8 hr after soman and throughout the remainder of the experimental period. Two different monkeys each were given two doses of sarin, 183 nmol/dose (one LD50) after 460 nmol of BuChE. No signs were observed. A third group of monkeys given 253 or 340 nmol (three and four LD50, respectively) of soman after 460 nmol of BuChE required 1 mg/kg of atropine i.v. 10 min postsoman, but recovered completely within 24 hr. Our results indicate that BuChE has the required properties to function as a biological scavenger to protect against the pharmacological and behavioral toxicity of OP poisons. PMID- 1941612 TI - Vascular actions of TA 3090, a novel analog of diltiazem: interaction with endothelium-dependent relaxation in canine femoral and coronary arteries. AB - The effects of a new 1,5-benzothiazepine calcium antagonist, TA 3090 (an analog of diltiazem), were analyzed in isolated canine femoral and coronary arteries suspended in organ chambers or studied in a bioassay system. TA 3090 (10(-9) to 10(-4) M) caused comparable relaxations in arterial rings with and without endothelium contracted by prostaglandin F2 alpha. Coronary arteries were more sensitive to the Ca++ antagonist. In both preparations, TA 3090 was more potent than diltiazem. In femoral (but not coronary) artery rings with endothelium, acetylcholine (10(-8) M) inhibited relaxations to TA 3090. Previous treatment of femoral or coronary arteries with TA 3090 (10(-6) M) had no effect on endothelium dependent relaxations to acetylcholine. In a bioassay system, TA 3090 (2 x 10(-7) M) caused partial reversal of acetylcholine-induced relaxation in perfused femoral arteries and superfused coronary arterial rings. The dihydropyridine enantiomer (-)-202,791 did not affect acetylcholine-induced relaxations and did not prevent the reversal by TA 3090. These data indicate that, in addition to a direct action on vascular smooth muscle, this novel benzothiazepine Ca(++) antagonist interferes with the synthesis/release of endothelium-derived relaxing factor stimulated by acetylcholine in canine femoral arteries. These findings, which are similar to those obtained with d-cis-diltiazem, support the hypothesis that a specific benzothiazepine-dependent mechanism(s) can suppress the production of endothelium-derived relaxing factor in endothelial cells. PMID- 1941613 TI - Antagonism of norepinephrine by clonidine in the isolated rat mesenteric vascular bed. AB - Experiments were done in isolated, perfused mesenteric vascular beds from Sprague Dawley rats. Bolus injections of norepinephrine (3-100 nmol) induced dose dependent increases in perfusion pressure with a maximum increase greater than 100 mm Hg. In the same dose range, clonidine had no effect on perfusion pressure. In the presence of an elevated pressure caused by constant infusions of norepinephrine (6-20 microM), bolus injections of clonidine (0.1-10 nmol) or acetylcholine (0.007-7 nmol) caused dose-related decreases in perfusion pressure. Procedures which damage endothelium (brief exposure to methylene blue or reactive oxygen radicals) abolished the depressor action of acetylcholine but only moderately reduced the depressor action of clonidine. The depressor action of clonidine was not antagonized by the alpha-2 adrenoceptor antagonist, idazoxan. Acetylcholine produced depressor responses in the presence of 5-hydroxy tryptamine or vasopressin, but clonidine did not. Dose-response curves to bolus doses of norepinephrine were shifted markedly to the right by an alpha-1 selective concentration of prazosin (1 nM) and were shifted to the right with depression of maximum by infusions of clonidine (0.3 and 1.0 microM). It is concluded that, in the mesenteric vasculature of the rat: 1) the role of alpha-2 adrenoceptors, in responses to clonidine, is minimal; 2) endothelial factors play little role, if any, in the depressor effects of clonidine and 3) clonidine has a potent ability to interfere with the alpha-1 adrenoceptor-mediated vasoconstriction induced by norepinephrine. This antagonistic action may be at the level of the receptor but could involve postreceptor steps. PMID- 1941614 TI - Characterization of bradykinin mediating pertussis toxin-insensitive biphasic response in circular muscle of the isolated guinea pig ileum. AB - The mechanisms underlying the biphasic response (BR) of the circular muscle of the guinea pig ileum (CMGPI) to bradykinin (BK) have been examined. Both BK and lysyl-BK (1 nM to 1 microM) caused graded contractions followed by relaxations of the CMGPI, yielding EC50 of 21 and 92 nM for contraction and of 10 and 27 nM for relaxation, respectively. The selective B1 receptor agonist Des-Arg9-BK was without effect up to 3 microM. The potencies of BK and lysyl-BK to evoke BR were markedly increased by enalapril (3 microM) and decreased by raising the preparation tone with the thromboxane A2/prostaglandin H2-mimetic U46619 (30 ng/ml). The BR of CMGPI to BK was unaffected by atropine, yohimbine, pyrilamine, propranolol, prazosin, phorbol ester, des-Arg9-[leu8]-BK (1 microM, each), tetrodotoxin (0.3 microM), [3,4,5-trimethoxybenzoic acid-8-(diethylamino) octyl ester (10 microM), [N-6-(aminohexyl)-5-chloro-1-naphthalenosulfonamide (10 microM), glibenclamide (0.3 microM), nordihydroguaiaretic acid (50 microM), phenidone (30 microM) or dexamethasone (0.1 microM). However, indomethacin (3 microM), ibuprofen (30 microM) and 3-amino, 1-(m-[trifluoromethyl] phenyl)2 pyrazoline (10 microM) each abolished the relaxant and increased the contractile response to BK, suggesting that a cyclo-oxygenase-derived eicosanoid mediates relaxation and limits contraction. Prostaglandin (PG) E2 (up to 100 nM) caused only graded relaxations, PGF2 alpha (up to 3 microM) and 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F2 alpha (up to 300 ng/ml) caused only contractions and the PGI2 analog iloprost was without effect up to 1 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941615 TI - Vanadate potentiates hypoxic pulmonary vasoconstriction. AB - Vanadate, an essential trace element and an inhibitor or stimulator of many enzymes, potentiates the hypoxic vasoconstriction in isolated lung preparations. However, the mechanism of action of vanadate in the lung circulation is unclear. We compared, in isolated rat lungs, the effect of vanadate (3 x 10(-5) M) on hypoxia-induced vasoconstriction with the vasoconstriction caused by angiotensin II, KCl or NaCN, and found that vanadate preferentially enhanced the hypoxia- and NaCN-induced pressor responses. Vanadate also shifted the stimulus-response curve for oxygen such that vasoconstriction occurred at a higher PO2 than in control lungs, indicating that vanadate had affected the oxygen sensing mechanism in the lungs. We postulated that vanadate might potentiate hypoxic vasoconstriction, in part, by activating a protein kinase C (PKC), and compared the effect of phorbol myristate acetate (PMA; 5 x 10(-8) M) on hypoxic vasoconstriction with that of vanadate. Both agents, PMA and vanadate, potentiated hypoxic vasoconstriction transiently and to a similar degree and the potentiation by both agents was blocked by staurosporine (1 microgram/ml), a PKC inhibitor, and 2-nitro-4 carboxyphenyl-N,N-diphenylcarbamate, a phospholipase C inhibitor, and partially reduced by the Ca++ entry inhibitor nifedipine. We conclude that the similarities between the action of PMA and vanadate in isolated lungs point toward an involvement of the PKC in the mechanism of vanadate-induced potentiation of hypoxic vasoconstriction. In addition, our data indicate that potentiation of hypoxic vasoconstriction by PMA or vanadate may occur, in part, independent of voltage-dependent Ca++ entry. PMID- 1941616 TI - Muscarinic stimulation of adenylate cyclase activity of rat olfactory bulb. I. Analysis of agonist sensitivity. AB - In rat olfactory bulb, stimulation of muscarinic receptors activates adenylate cyclase. In the present study we have examined a variety of muscarinic receptor stimulants to characterize the agonist profile of this response. Analysis of agonist concentration-response curves revealed the following rank order of potency: oxotremorine-M greater than oxotremorine greater than BM5 greater than acetylcholine greater than carbachol = methacholine greater than (+/-)muscarine greater than arecoline greater than pilocarpine greater than RS 86 greater than McN-A-343 greater than bethanechol. Acetylcholine, oxotremorine-M, carbachol, (+/ )muscarine and metacholine behaved as full agonists, whereas the other stimulants displayed lower efficacies. The slope values of the concentration-response curves were close or equal to 1, except those of the carbachol and pilocarpine curves, which showed values significantly lower than 1. Moreover, the slope of the pilocarpine curve was differentially changed by the M1 antagonist pirenzepine and the M2 antagonist AF-DX 116. The agonist profile of the muscarinic stimulation of adenylate cyclase in the olfactory bulb correlated well with that exhibited by the muscarinic inhibition of the enzyme activity in the striatum, suggesting that the two responses are mediated by a similar receptor subtype. Sodium ion modulated the agonist affinity for both adenylate cyclase-coupled receptor systems. PMID- 1941617 TI - Comparison of inhibitory potency by nonpeptide angiotensin II receptor antagonists PD123177 and DuP 753 on proximal nephron and renal transport. AB - The nonpeptide angiotensin II receptor antagonists, DuP 753 and PD123177, have been recently proposed to efficiently discriminate between two receptor subtypes. Because angiotensin II uses two signaling systems to control transport in the proximal tubule, the hypothesis was entertained that angiotensin-regulated proximal reabsorption might be transduced through two receptor subtypes and, therefore, have two components, sensitive to either DuP 753 or PD123177. Using in vivo microperfusion in the rat, a maximally effective dose of PD123177 (60 or 120 mg/kg, i.v.) had a powerful inhibitory effect on transport in the S1 proximal tubule, significantly (P less than .001) reducing bicarbonate absorption by 50% (360 +/- 4 to 179 +/- 8 peq/mm.min), chloride absorption by 38% (211 +/- 1 to 131 +/- 4 peq/mm.min) and sodium and water absorption by 32% (5.7 +/- 0.1 to 3.9 +/- 0.5 nl/mm.min). These results were only slightly different than previously reported effects on proximal solute and water absorption by DuP 753 (10 mg/kg). The two drugs demonstrated virtually no additivity in their transport inhibitory effects. Although downstream reabsorptive elements compensate for the powerful action of PD123177 in the earliest segment of the nephron, we also showed, using free-flow micropuncture and clearance techniques, that PD123177 induces a substantial diuresis, natriuresis and chloruresis, again similar in magnitude to DuP 753. These results suggest PD123177 has diuretic potency roughly equivalent to that of DuP 753, but do not lend support to the simple thesis that there are two separately acting receptor-signal transduction systems in the proximal tubule for angiotensin II. PMID- 1941618 TI - Polymorphic and monomorphic expression of arylamine carcinogen N acetyltransferase isozymes in tumor target organ cytosols of Syrian hamsters congenic at the polymorphic acetyltransferase locus. AB - A number of human epidemiological investigations suggest a relationship between acetylator phenotype and the incidence and/or severity of tumors caused by exposure to arylamine carcinogens. Conclusions drawn from these investigations can be compromised by a variety of environmental and other genetic factors. To eliminate variability in these other factors, our laboratory recently completed construction of homozygous rapid (Bio. 82.73/H-Patr), heterozygous intermediate (Bio. 82.73/H-Patr/Pat(s)) and homozygous slow (Bio. 82.73/H-Pat(s)) acetylator congenic hamsters. The purpose of the present study was to assess the utility of this congenic hamster model for investigations into the relationship between acetylator genotype and arylamine carcinogenesis. We report the expression of acetylator genotype-dependent (polymorphic) and acetylator genotype-independent (monomorphic) N-acetyltransferase isozymes in hepatic cytosols. The hepatic polymorphic N-acetyltransferase isozyme isolated from the congenic hamsters expressed clearly acetylator-genotype dependent (Patr greater than Patr/Pat(s) greater than Pat(s)) N-acetylation towards p-aminobenzoic acid, 4-aminobiphenyl, 2-aminofluorene, p-aminophenol, 1-aminopyrene, 5-aminosalicylic acid, beta naphthylamine, 3,4-dichloroaniline, 3,2'-dimethyl-4-aminobiphenyl and p phenetidine. Acetylator genotype-dependent N-acetylation for a number of arylamines also was observed in liver, colon, kidney and urinary bladder cytosols derived from the congenic hamster lines, including arylamines highly carcinogenic to hamster colon and urinary bladders. It is concluded that the congenic hamster model will be useful in studies to delineate the role of acetylator genotype in the incidence or severity of arylamine tumors. PMID- 1941619 TI - Calcium currents and peptide release from neurohypophysial terminals are inhibited by ethanol. AB - The effects of EtOH on peptide release and on high-threshold, voltage-activated calcium (Ca++) channels were examined in acutely dissociated rat neurohypophysial terminals. These terminals release the peptide hormones, arginine vasopressin (AVP) and oxytocin. Release of AVP from isolated intact neurohypophyses, induced by either electrical stimulation or elevated potassium, was inhibited by clinically relevant concentrations of EtOH. "Whole-cell" patch-clamp recording methods were used to study the effects of EtOH on voltage-activated Ca++ currents (ICa) in the peptidergic nerve terminals. Amplitudes of both fast-inactivating ICa and long-lasting ICa were reduced in EtOH, and the reduction in ICa did not result from a shift in its current-voltage or steady-state inactivation relationships. Only the fast-inactivating component recovered after removal of EtOH. The effects of EtOH on ICa could not be attributed to changes in osmolarity. In contrast to ICa, the fast, transient K+ current was insensitive to EtOH. These results suggest that EtOH-induced reduction of ICa in the peptidergic nerve terminals produces a decrease in AVP release, resulting in lowered plasma AVP levels. PMID- 1941620 TI - Location of penetration and metabolic barriers to levobunolol in the corneal epithelium of the pigmented rabbit. AB - The objective of this study was to determine which of the five or six corneal epithelial layers was rate-limiting in the corneal penetration and metabolism of levobunolol in the pigmented rabbit. Corneal penetration and metabolism were evaluated using the isolated cornea in the modified Ussing chamber. Levobunolol and its metabolite, dihydrolevobunolol, were assayed by reversed phase high performance liquid chromatography using spectrophotometric detection. EDTA (0.1 and 0.5%) and benzalkonium chloride (0.005-0.05%) were used to disrupt the integrity of the corneal epithelial layers. EDTA, which loosened the tight junctions between the superficial corneal epithelial cells, reduced both the transcorneal flux and metabolism of levobunolol. In contrast, benzalkonium chloride, which disrupted the integrity of the outermost corneal epithelial layers, enhanced the transcorneal levobunolol flux while reducing its extent of metabolism. The extent of enhancement in transcorneal flux afforded by 0.025% benzalkonium chloride was comparable to that seen in the deepithelized cornea. Within 5 min of contact by the corneal epithelium with this preservative, the ratio of dihydrolevobunolol concentration on the endothelial to the epithelial side was reduced by two-thirds. Although direct confirmation is required, the above findings are consistent with the hypothesis that the rate-limiting layer to corneal penetration of levobunolol resides in the outermost two to three layers of the corneal epithelium, whereas the metabolic barrier resides in deeper lying regions. PMID- 1941621 TI - A new type of vasodilator, HA1077, an isoquinoline derivative, inhibits proliferation of bovine vascular smooth muscle cells in culture. AB - The effects of a newly developed vasodilator agent, HA1077 [1-(5 isoquinolinesulfonyl)-homopiperazine hydrochloride], were investigated on the proliferation of cultured bovine aortic vascular smooth muscle cells (VSMC). HA1077 (10-100 microM) inhibited both fetal calf serum-induced proliferation and [3H]thymidine incorporation into DNA of the growth-arrested VSMC in a dose dependent manner. When quiescent cells were stimulated with platelet-derived growth factor followed by insulin, HA1077 (1-30 microM), administered together with either stimulation, showed dose-dependent inhibition of [3H]thymidine incorporation. Further reduction of [3H]thymidine incorporation was observed when HA1077 was present at both stimulations, suggesting that HA1077 suppresses DNA synthesis acting in both competence and progression stages. After stimulation with fetal calf serum, quiescent VSMC started and ceased DNA synthesis in 15 to 18 hr and 24 hr, respectively. HA1077 inhibited [3H]thymidine incorporation when it was added either from 12 hr to 15 hr or from 21 hr to 24 hr after serum stimulation. In addition, when percent inhibition of [3H]thymidine incorporation by continuous exposure to HA1077 was examined as a function of the time it was added, reductions of the value were observed at 0 to 3 hr, 12 to 18 hr and 21 to 24 hr. Thus, we concluded that HA1077 suppresses DNA synthesis of bovine VSMC acting at the G0/G1 and the G1/S phase transitions and also in the S phase of the cell cycle. It is suggested that this agent may act as a potent inhibitor of VSMC proliferation as well as a vasodilator. PMID- 1941622 TI - Immune status and survival of opiate- and cocaine-treated mice infected with Friend virus. AB - In as much as the immunomodulatory effects of opiates and cocaine are known to modify spontaneous host defenses against infection, we investigated the effects of morphine, pentazocine and cocaine on the time course of Friend virus infection in mice. Repeated i.p. injections with increasing doses of morphine hydrochloride (10-100 mg/kg for 10 days before infection, a dose regimen which induced tolerance to the acute antinociceptive effects of the drug, followed by 30 mg/kg for 14 days postinfection) did not increase the mortality due to Friend virus infection. This regimen did not significantly affect the immune response of infected mice assessed in terms of delayed hypersensitivity (ear thickness) and the hemagglutination assay. In contrast, a single challenge with a large dose of morphine (up to 300 mg/kg), which is not lethal in noninfected mice, increased mortality markedly (up to 100%) in infected mice when administered at day 14 or 21 postinfection. Repeated i.p. injections with pentazocine (50 mg/kg b.i.d. for 5 days before infection, followed by 30 mg/kg for 14 days postinfection) had no influence on mortality or immune responses in infected mice; similar results were obtained with a single high-dose injection (up to 100 mg/kg). Lastly, repeated i.p. injections of cocaine, using the same experimental procedure as that for pentazocine, decreased immune responsiveness and slightly increased mortality, whereas a single injection was devoid of lethal effect. These findings suggest that chronic opioid treatment does not lower host resistance to viral infection but that the latter could increase the toxicity of a single high dose of morphine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941623 TI - Arachidonic acid and bradykinin share a common pathway to release neuropeptide from capsaicin-sensitive sensory nerve fibers of the guinea pig heart. AB - The ability of arachidonic acid (AA) and bradykinin to release calcitonin gene related peptide-like immunoreactivity (CGRP-LI) from capsaicin-sensitive primary afferents was studied in guinea pig isolated and perfused heart. Infusion of AA (50 microM to 5 mM, 0.5 ml/min over 2 min) produced a remarkable and dose dependent CGRP-LI release that was abolished by in vitro capsaicin (10 microM) pretreatment or in the presence of indomethacin (10 microM). The capsaicin antagonist ruthenium red (10 microM) did not affect the CGRP-LI release produced by AA, whereas it blocked that produced by capsaicin (10 microM). In vitro capsaicin pretreatment reduced the increase in heart rate evoked by AA, whereas it did not affect the increase in coronary flow and decrease in contractility. Bradykinin (10 microM, 0.5 ml/min over 2 min) induced CGRP-LI release in a similar manner to that produced by AA, with the only difference being that in the presence of indomethacin, a residual increase in CGRP-LI outflow was still observed. AA increased the outflow of 6-keto-prostaglandin (PG) F1 alpha, PGE2 and leukotriene B4, whereas bradykinin enhanced only the release of 6-keto-PGF1 alpha. Infusion of either PGI2 or PGE2 (1-100 microM) released CGRP-LI in a dose dependent manner and with a similar potency. PGI2 (100 microM)- or PGE2 (100 microM, 0.5 ml/min over 2 min)-evoked release was abolished by previous exposure to capsaicin and not affected by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941624 TI - Renal selective N-acetyl-L-gamma-glutamyl prodrugs. III. N-acetyl-L-gamma glutamyl-4'-aminowarfarin is not targeted to the kidney but is selectively excreted into the bile. AB - The pharmacokinetics of N-acetyl-L-gamma-glutamyl-4'-aminowarfarin (AGAW) was studied in the rat. The aim of this prodrug was to cause a renal-specific inhibition of the vitamin K cycle as a result of renal-specific release of the active drug 4'-aminowarfarin (AW). In vitro, it was found that kidney and liver homogenates and cytosol were able to convert the prodrug. In vivo, plasma concentrations of AW rose only slowly after a dose of 10 mg/kg AGAW i.v. to give a maximum concentration of about 3 micrograms AW/ml at t = 14 to 24 h. The tissue distribution of AGAW and AW was measured after 10 mg/kg AGAW i.v. It was found that AGAW did not accumulate in the kidney (9.7 micrograms/g in the kidney; 83 micrograms/ml in plasma at t = 60 min). AW concentrations were very low (0.1 microgram/ml or mg at t = 60 min). These results suggest that AGAW is not transported via a carrier into the kidney. The uptake of AGAW in vitro by rat kidney slices was investigated. It was found that AGAW did not accumulate in the slices. Neither did AGAW influence the accumulation of N-acetyl-gamma-glutamyl sulfamethoxazole in kidney slices. A second explanation for the lack of selectivity of AGAW in vivo could be its high (approximately 90%) plasma protein binding. Instead of being targeted to the kidney, however, AGAW was found to be excreted via a carrier-mediated mechanism into the bile: 50% of the dose was recovered unchanged in the bile within 3 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941625 TI - Discriminative-stimulus effects of quipazine and l-5-hydroxytryptophan in relation to serotonin binding sites in the pigeon. AB - The 5-hydroxytryptamine (serotonin; 5-HT) agonists, RU-24969 [5-methoxy 3 (1,2,3,6-tetrahydro-4-pyridinyl)1H-indole, succinate], ipsapirone [2-(4-[4-(2 pyrimidinyl)-1-piperazinyl]butyl)-1,2- benzisothiazol-3-(2H)one-1,1 dioxidehydrochloride], 8-hydroxy-N,N-dipropyl-2-aminotetralin, lysergic acid diethylamide, fenfluramine and N,N-dimethyltryptamine were studied in pigeons trained to discriminate quipazine (1.0 mg/kg) from saline and in pigeons trained to discriminate I-5-HTP (18.0 mg/kg) from saline. Lysergic acid diethylamide, quipazine and fenfluramine generalized to the training stimulus in both groups of pigeons. N,N-dimethyltryptamine generalized to quipazine in all pigeons tested whereas N,N-dimethyltryptamine generalized to I-5-HTP in most pigeons tested. The natural substrate 5-HT and agonists with affinities for the 5-HT1 receptor and its subtypes (8-hydroxy-N,N-dipropyl-2-aminotetralin, ipsapirone, and RU-24969) only generalized in the I-5-HTP-trained pigeons. Equilibrium binding experiments using the ligands [3H]-5-HT and [3H]ketanserin were performed with six areas of pigeon brain and six homologous areas of rat brain. Two populations of 5-HT binding sites were found in brains of both species; one defined by high-affinity binding of [3H]-5-HT and the other defined by high-affinity binding of [3H]ketanserin. Kd values were similar for the two ligands in brains of both species. 5-HT, RU-24969 and ipsapirone displaced [3H]-5-HT but not [3H]ketanserin from pigeon brain membranes. The present study suggests that, in the pigeon, the 5-HT2 receptor might mediate the discriminative-stimulus effects of quipazine, whereas the 5-HT1 receptor might mediate the effects of I-5-HTP. PMID- 1941626 TI - Influence of debrisoquine phenotype and of quinidine on mexiletine disposition in man. AB - Mexiletine is a low clearance drug which undergoes extensive metabolism in man. In vitro studies with human liver microsomes have suggested that major oxidation pathways of mexiletine are predominantly catalyzed by the genetically determined debrisoquine 4-hydroxylase (cytochrome P450IID6) activity. In this study, we investigated the role of debrisoquine polymorphism and the effects of low dose quinidine, a selective inhibitor of cytochrome P450IID6, on the disposition of mexiletine. Fourteen healthy volunteers, 10 with the extensive metabolizer (EM) and 4 with the poor metabolizer (PM) phenotype, received a single 200-mg dose of mexiletine hydrochloride orally on two occasions (1 week apart), once alone and once under steady-state conditions for quinidine (50 mg QID). During the phase mexiletine alone, total clearance, nonrenal clearance and partial metabolic clearance of mexiletine to hydroxymethylmexiletine, to m-hydroxymexiletine and to p-hydroxymexiletine were decreased in PM compared to EM (all P less than .05). In EM, quinidine decreased mexiletine total clearance from 621 +/- 298 to 471 +/- 214 ml/min (mean +/- S.D.; P less than .05) and mexiletine nonrenal clearance from 583 +/- 292 to 404 +/- 188 ml/min (P less than .05). Moreover, quinidine increased mexiletine elimination half-life in EM from 9 +/- 1 to 11 +/- 2 h (P less than .05). In these subjects, partial metabolic clearance to hydroxymethylmexiletine, m-hydroxymexiletine and p-hydroxymexiletine were decreased by quinidine coadministration 5-, 4- and 7-fold, respectively, whereas partial metabolic clearance to N-hydroxymexiletine was unaffected. Changes induced by quinidine in EM were correlated to their debrisoquine metabolic ratio. Thus, genetically determined or pharmacologically induced modulation of cytochrome P450IID6 activity represents a major determinant of mexiletine disposition. PMID- 1941628 TI - Determination and metabolism of dithiol chelating agents. XII. Metabolism and pharmacokinetics of sodium 2,3-dimercaptopropane-1-sulfonate in humans. AB - The sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS) is used p.o. for the treatment of chronic lead and Hg intoxication in humans. The metabolism and pharmacokinetics of DMPS were determined after p.o. administration of 300 mg of DMPS to each of 10 normal young men. The absorbed DMPS was metabolized rapidly and extensively to a disulfide form(s). By 24 hr after DMPS administration, the area under the blood concentration-time curve of unaltered DMPS was 3.9 compared to 143 for altered DMPS. Altered DMPS is the difference between total DMPS and unaltered DMPS. Unaltered DMPS is the unbound, parent compound;, total DMPS consists of unaltered DMPS plus oxidized [disulfide] DMPS which is determined after reduction with dithiothreitol. In blood the altered form was confined to plasma. By 15 hr, only 3.7% of the administered DMPS was excreted in the urine as unaltered DMPS and 38.7% as altered DMPS. The unaltered and altered DMPS represented 9 and 91%, respectively, of the total amount of DMPS in the urine. Altered DMPS was converted to unaltered DMPS by treatment with dithiothreitol, which indicates that the altered DMPS is a disulfide(s). There was a high correlation between the urinary excretion of Hg and the urinary excretion of unaltered DMPS (r = 0.920 +/- 0.022 S.E.). PMID- 1941627 TI - Comparative pharmacology of the nitrobenzylthioguanosine-sensitive and -resistant nucleoside transport mechanisms of Ehrlich ascites tumor cells. AB - A variety of nucleoside transport inhibitors and substrates were compared for their capacities to inhibit the zero-trans influx of [3H]uridine in Ehrlich ascites tumor cells. ATP-depleted cells accumulated [3H]uridine primarily by facilitated diffusion (Vmax = 16 pmol/sec/microliter cell water) via both nitrobenzylthioguanosine (NBTGR)-sensitive (IC50 = 0.53 nM, 100 microM [3H]uridine) and NBTGR-resistant (IC50 = 71 microM, 100 microM [3H]uridine) mechanisms with uridine Km estimates of 99 and 284 microM, respectively. Dilazep also distinguished between the transporter subtypes with IC50 values of 1.4 nM and 1.8 microM, respectively, for inhibiting 100 microM [3H]uridine influx. Incubation of cells with 50 nM NBTGR allowed the selective study of inhibitor effects on NBTGR-resistant [3H]uridine influx. Dipyridamole, cyclopentyladenosine, 2-phenylaminoadenosine, etoposide, teniposide, diazepam, chlordiazepoxide, triazolam and the lidoflazine derivative 2-(aminocarbonyl)-N-(4 amino-2,6-dichlorophenyl)-4-[5,5-bis-(4- fluorophenyl)pentyl]-1 piperazineacetamide (R75231), were significantly less potent as inhibitors of NBTGR-resistant influx, when compared with their capacities to inhibit the total mediated influx of [3H]uridine. In contrast, 2-fluoroadenosine, 2 chloroadenosine, 5'-N-ethylcarboxamidoadenosine and soluflazine were relatively more effective as inhibitors of the NBTGR-resistant component. Mioflazine, a compound related to both soluflazine and R75231, did not distinguish between transporter subtypes. The NBTGR-resistant transporter also had a distinctive substrate specificity; guanosine, 2'-deoxyguanosine, cytidine and 2' deoxycytidine were significantly less effective as inhibitors of NBTGR-resistant [3H]uridine influx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941629 TI - Serotonin (5-HT)3 receptor blocking activities of YM060, a novel 4,5,6,7 tetrahydrobenzimidazole derivative, and its enantiomer in anesthetized rats. AB - YM060 [(R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimida zol e hydrochloride], is structurally independent of other 5-HT3 receptor antagonists. We investigated in vivo 5-HT3 receptor blocking activity of YM060 and compared results with those of its enantiomer (S-form), ondansetron (GR38032F), granisetron (BRL43694), ICS205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester], LY277359 [endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8 azabicyclo[3.2.1] oct-3-yl)-7-benzofuran-carboxamide-(Z)-2-butenedioate (1:1)], Y25130 [(+-)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4- dihydro 2H-1,4-benzoxazine-8-carboxamide hydrochloride] and zacopride [(R,S)4-amino-N-[1 azabicyclo (2.2.2)oct-3-yl]-5-chloro-2-methoxybenzamide(E)-2-butenedioat e]. YM060 injected i.v. dose-dependently inhibited the reduction in heart rate induced by 5-HT (30 micrograms/kg i.v.) in rats (von Bezold-Jarisch reflex) with an ED50 value of 0.036 (0.031-0.041) micrograms/kg (n = 3-5). Based on these values, YM060 was 53, 18, 23, 16, 11 and 4 times as potent as ondansetron, granisetron, ICS205-930, LY277359, Y25130 and zacopride, respectively. The S-form of YM060 also inhibited 5-HT-induced bradycardia, but with a potency approximately 250 times less than that of YM060 (R-form). YM060 dosed p.o. also inhibited 5-HT-induced bradycardia with an ED50 value of 0.59 (0.44-0.80) micrograms/kg (n = 3-5), indicating the drug to be 387, 66, 97, 6 and 16 times more potent than ondansetron, granisetron, ICS205-930, LY277359 and Y25130, respectively, but 2 times less potent than zacopride. Bioavailability of YM060 based on the p.o.-to-i.v. ED50 ratio (p.o./i.v. = 16) was lower than those of zacopride (2) and LY277359 (6), similar to that of Y25130 (22) and better than those of ondansetron (109), granisetron (60) and ICS205-930 (71).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941630 TI - Effect of ketoconazole on methylprednisolone pharmacokinetics and receptor/gene mediated pharmacodynamics. AB - The disposition of methylprednisolone (MPL) and its metabolite, methylprednisone, and the receptor/gene-mediated pharmacodynamics of methylprednisolone were examined in control and ketoconazole-treated rats. Oral doses of ketoconazole (50 mg/kg/day) for 3 days increased plasma MPL clearance by 50% (NS) with no change in volumes of distribution. The mean residence time decreased from 0.60 +/- 0.15 (control) to 0.43 +/- 0.10 hr with ketoconazole (P less than .05) after 5 mg/kg of MPL (free alcohol). The methylprednisone to MPL area under the curve ratio decreased from 0.19 +/- 0.04 in control to 0.14 +/- 0.03 in ketoconazole-treated rats (P less than .05) due to altered interconversion between these steroids. An improved pharmacokinetic/dynamic receptor/gene-mediated model characterized the steroid receptor binding and induction of tyrosine aminotransferase activity after i.v. MPL sodium succinate (10 mg/kg). In contrast to previous in vitro studies, ketoconazole at maximally tolerated doses failed to antagonize the steroid receptor-mediated activity of MPL. Although ketoconazole at high concentrations competitively inhibited the in vitro binding of steroid to hepatic receptors, no in vivo inhibition was detected after large p.o. ketoconazole doses. Efficiency of tyrosine aminotransferase induction was slightly enhanced in ketoconazole animals. Pharmacokinetic/dynamic factors accounting for the lack of antiglucocorticoid activity primarily include the low ketoconazole receptor binding affinity. PMID- 1941631 TI - Serotoninergic involvement in ethanol-induced alterations of thermoregulation in long-sleep and short-sleep mice. AB - The effect of ethanol and pentobarbital on in vivo tryptophan hydroxylase activity and its relationship to drug-induced alterations of thermoregulation was examined in long-sleep (LS) and short-sleep (SS) mice. Serotonin function was measured in both the presence and absence of ethanol or pentobarbital in six discrete brain regions. Differences in basal levels of serotonin, 5-hydroxyindole acetic acid or in vivo tryptophan hydroxylase (TpH) activity were found only in the hypothalamus and dorsal raphe nuclei (SS slightly higher). Ethanol (4.2 g/kg i.p) caused significant reductions in in vivo TpH activity in the dorsal and pontine-medullary raphe nuclei and hypothalamus (putative thermoregulatory areas) in both LS (50-60% decrease) and SS (15-30% decrease) mice, but it had no effect on TpH activity in the striatum, cortex or hippocampus. The greater degree of ethanol-induced reduction in TpH activity in LS mice was associated with a greater degree of hypothermia (LS, 4.2 degrees C vs SS, 2.0 degrees C). Pentobarbital had equivalent effects in LS and SS mice on TpH activity in central nervous system thermoregulatory areas (decreases of 40-60%) and on body temperature (decreases of 6.8-7.5 degrees C). When the mice were given ethanol at an elevated environmental temperature (34 degrees C) the hypothermia was almost abolished completely, but depressant effects on TpH activity remained, suggesting that ethanol-induced decreases in TpH activity were direct effects and not secondary to hypothermia. Alterations in ethanol or pentobarbital elimination did not appear to account for the observed differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941632 TI - Pharmacology of DuP 532, a selective and noncompetitive AT1 receptor antagonist. AB - DuP 532 (2-propyl-4-pentafluoroethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl- 4 yl)methyl]imidazole-5-carboxylic acid) inhibited the specific binding of [125I]angiotensin II (AII) for the subtype receptor AT1 in rat adrenal cortical membranes with an IC50 of 3.1 X 10(-9) M, but not the [125I]AII binding for the subtype AT2 sites in rat adrenal medulla tissues. It inhibited the contractile response to AII selectively and noncompetitively in the isolated rabbit aorta with a KB value of 1.1 X 10(-10) M. The selective AII antagonism was confirmed in the guinea pig ileum and the pithed rat. In conscious rats, DuP 532 inhibited the AII-induced pressor effect, aldosterone secretion, and water drinking induced by AII. In conscious renal hypertensive rats, DuP 532 decreased blood pressure with i.v. and p.o. ED30 of 0.02 and 0.21 mg/kg, respectively. The antihypertensive effect of DuP 532 at 0.3 to 3 mg/kg p.o. lasted for at least 24 hr. In conscious spontaneously hypertensive rats, DuP 532 given i.v. or p.o. at 0.3 to 3 mg/kg reduced blood pressure dose-dependently. DuP 532, at doses up to 100 mg/kg i.v., did not cause a pressor response in conscious normotensive rats, suggesting lack of agonism. DuP 532 exerted selective AII antagonism in conscious dogs. In conscious furosemide-treated dogs, DuP 532 given either at 0.3 and 1 mg/kg i.v. or at 1 to 10 mg/kg p.o. decreased blood pressure. As the AT1 receptors are responsible for AII-induced vasoconstriction, aldosterone secretion, and water drinking, our study indicates that DuP 532 is a potent, orally active, selective, and noncompetitive AT1 receptor antagonist and antihypertensive agent. PMID- 1941633 TI - Arrhythmogenic activities of antiarrhythmic drugs in conscious hypokalemic dogs with atrioventricular block: comparison between quinidine, lidocaine, flecainide, propranolol and sotalol. AB - In order to create and evaluate a model sensitive to QT-dependent proarrhythmic effects of drugs, a long QT syndrome was produced in chronically instrumented dogs with bradycardia and hypokalemia. Bradycardia (mean cycle length: 1495 +/- 78 msec) was provided by permanent atrioventricular block and hypokalemia (K+ = 2.6 +/- 0.05 mmol/l) by high doses of diuretics. To evaluate that model, six of these conscious dogs were subjected to quinidine, flecainide, lidocaine, propranolol and sotalol infusions. In crossover design, drugs were infused i.v. at rates allowing stable and nontoxic drug plasma levels during the experiment. Four-lead ECGs were recorded for arrhythmias for 30 min before (base line) and 75 min after onset of infusion. Ventricular cycle length was increased dramatically by sotalol, lidocaine and propranolol (+618 +/- 192, +388 +/- 125 and +329 +/- 114 msec, respectively) and QT interval was increased by sotalol, quinidine and flecainide (+56 +/- 8, +31 +/- 7.9 and +20 +/- 5.7 msec, respectively). Quinidine and sotalol, but not flecainide, propranolol or lidocaine, exhibited significant arrhythmogenic activities. During quinidine infusion, most dogs exhibited some ventricular arrhythmias whose most severe forms were runs of ventricular tachycardia. These arrhythmias were suppressed by pacing at high rates. During sotalol infusion, five out of six dogs exhibited typical "torsades de pointes." This incidence was not related to the slowing effects of sotalol on idioventricular pacemakers, because a similar incidence was obtained in five complementary dogs paced at 40 bpm. It could be related to dose, because torsades de pointes occurred only once in another group of five dogs receiving half the dose used in the controlled study. Only quinidine and sotalol, but not propranolol, flecainide or lidocaine, are clinically associated to torsades de pointes. They were also the only drugs associated with proarrhythmic events in the present study, a fact suggesting that QT-dependent arrhythmogenic effects of drugs can be reliably evaluated in conscious hypokalemic dogs with complete atrioventricular block. PMID- 1941634 TI - Inhibition by salicylic acid of the activation and thus oxidation of long chain fatty acids. Possible role in the development of Reye's syndrome. AB - Administration of either aspirin or salicylic acid (3 mmol.kg-1 b.wt. i.p.) decreased by 50 and 65%, respectively, the in vivo oxidation of [U-14C]palmitic acid to [14C]CO2 in mice; after salicylic acid administration, exhalation of [14C]CO2 from [1-14C]palmitic acid, [1-14C]octanoic acid or [1-14C]butyric acid was decreased by 87, 33 and 38%, respectively. Inhibition lasted 9 hr. It was associated with markedly decreased blood glucose concentrations and increased plasma ketone bodies. Repeated administration of salicylic acid (2 mmol.kg-1 i.p. every 8 hr) tripled hepatic triglycerides and produced mild microvesicular steatosis of the liver at 22 hr in fasted mice. In vitro, salicylic acid (1.5 mM) had no or little effect on the formation of beta-oxidation products from [1 14C]octanoic or [1-14C]palmitoyl-L-carnitine, in the presence of ATP, carnitine (40 microM) and coenzyme A (40 microM), but decreased by 51% that from [1 14C]palmitic acid. In the latter system, increasing the concentrations of coenzyme A and carnitine to 200 microM suppressed the inhibitory effect of salicylic acid. Salicylic acid (1.5 mM) decreased by 80% the in vitro mitochondrial formation of palmitoyl-coenzyme A from [1-14C]palmitic acid and 10 microM coenzyme A; again, increasing the concentration of coenzyme A prevented inhibition. We conclude that salicylic acid decreases the mitochondrial activation and thus beta-oxidation of long chain fatty acids, presumably by sequestering extramitochondrial coenzyme A and possibly carnitine. PMID- 1941635 TI - Systemic vascular effects of cyclosporin A treatment in normotensive rats. AB - The immunosuppressive drug cyclosporin A (CsA) frequently induces hypertension, but the mechanism(s) is unknown. Thus, we examined the mechanism(s) by which CsA increases arterial blood pressure (MAP) in the normotensive rat. Three different treatment modalities were used. First, chronic CsA treatment (20 mg/kg/day, s.c., for 1 week) significantly increased MAP from 109.6 +/- 2.3 mm Hg to 125.8 +/- 2.9 mm Hg (P less than .05). Second, subacute i.v. infusion of CsA (20 mg/kg daily for 3 days) increased MAP to even higher values (140.5 +/- 2.3 mm Hg), which correlated significantly with the highest circulating values of the drug. The pressor effect after i.v. infusion appears to be unrelated to endogenous release of catecholamines, because phentolamine, which abolishes the response to exogenous norepinephrine, failed to prevent the CsA-induced pressor response. Third, i.v. bolus injections of CsA (10-20 mg/kg) evoked immediate, dose dependent and short-lasting increases in MAP (+15-25 mm Hg) in both anesthetized and conscious rats. Ganglionic blockade did not prevent this effect, rather, a 2- to 3-fold increase in amplitude (+40-60 mm Hg) and duration (+30-45 min) of the CsA-induced pressor response was observed in anesthetized rats. Heart rate was not increased significantly by either acute or chronic administration of CsA. Our results suggest that both CsA-induced pressor responses and hypertension are due to a peripheral action unrelated to sympathetic outflow. Furthermore, CsA's hypertensive effect is accompanied by severe morphological changes in the vascular endothelium and smooth muscle cells. In addition, CsA-treated rats showed significantly attenuated vasodilatory responses to prostacyclin and sodium nitroprusside, and increased pressor responses to norepinephrine. Thus, a direct vascular action of CsA is likely to contribute to the alterations on systemic vascular responsiveness, as well as to the hypertensive effect of the drug. PMID- 1941636 TI - Sensitization to psychostimulants and stress after injection of pertussis toxin into the A10 dopamine region. AB - An augmentation of psychostimulant-induced motor activity, termed sensitization, occurs with daily treatment and can last for months or years. At least in part, sensitization results from a long-term change in mesocorticolimbic dopamine transmission and may involve a disinhibition of dopamine neurons. Dopamine D2 autoreceptors and gamma-aminobutyric acidB (GABAB) receptors provide tonic inhibition to dopamine neurons via a G protein-mediated increase in K+ efflux. To evaluate the role of these inhibitory mechanisms in sensitization, pertussis toxin (PTX) was injected into the A10 dopamine region to uncouple the receptors via ADP-ribosylation of G proteins. In this study we demonstrated a significant augmentation in cocaine-stimulated motor activity, at doses greater than 3.0 mg/kg, 14 days after intra-A10 injection of PTX. Also, amphetamine-, but not morphine- or caffeine-stimulated motor activity was significantly augmented 2 weeks after PTX pretreatment. In vivo microdialysis revealed an augmentation of cocaine-induced increases in extracellular dopamine in the nucleus accumbens 14 days after PTX pretreatment. Pretreatment in the A10 region with the GABAB agonist baclofen, blocked cocaine-stimulated motor activity in control animals, but not in PTX-pretreated animals, indicating that the PTX treatment had uncoupled the GABAB receptor. Footshock stress activates mesocortical dopamine transmission, and postmortem tissue levels of dihydroxyphenylacetic acid and homovanillic acid in the prefrontal cortex were increased in PTX-pretreated animals. We hypothesize that the sensitized responses to cocaine, amphetamine and stress produced by PTX results from a decrease in dopamine D2 and GABAB-mediated inhibitory control of A10 dopamine neurons. PMID- 1941637 TI - Hyperpolarization of denervated skeletal muscle by lemakalim and its antagonism by glybenclamide and tolbutamide. AB - Innervated skeletal muscles are endowed with K+ channels activatable by K+ channel openers. It is of interest to know whether the denervation-induced depolarization is due to a deficiency of such a K+ channel. In denervated mouse diaphragm, lemakalim, a K+ channel opener, effectively hyperpolarizes membrane and reduces membrane resistance, spontaneous activity as well as twitch force reversibly. Reductions of transmembrane K+ gradient diminish the lemakalim induced hyperpolarization. In voltage-clamped fiber, lemakalim induces a long lasting outward current. A current clamp experiment suggests a reversal potential of around -90 mV. On innervated diaphragm, lemakalim hyperpolarizes membrane and increases conductance if the muscle is predepolarized by anodal current. Lemakalim, however, is much less effective in overcoming the depolarization caused by crotamine, which activates Na+ channel. The effects of lemakalim are not attenuated by blockades of membrane Na+, Ca++ and Cl- permeabilities. Glybenclamide and tolbutamide, blockers of ATP-regulated K+ channel, antagonize the effects of lemakalim at low concentrations and produce slight membrane hyperpolarizations in denervated muscle, but marked membrane depolarizations in innervated muscle at higher concentrations. Cs+ depolarizes both innervated and denervated diaphragms and reduces the hyperpolarizing effect of lemakalim. The results suggest that lemakalim hyperpolarizes denervated muscle via glybenclamide sensitive K+ channels. It is inferred that a reduction of membrane K+ conductance rather than an increase of Na+ or Ca++ conductance contributes to the denervation induced depolarization. PMID- 1941638 TI - Actions of intravenous magnesium on ventricular arrhythmias caused by acute myocardial infarction. AB - Although the antiarrhythmic properties of magnesium are well recognized, its mechanisms of antiarrhythmic action are poorly understood. This study was designed to characterize the effects of magnesium on ventricular tachyarrhythmias related to acute myocardial infarction (MI) in dogs. When the circumflex coronary artery was occluded repeatedly for 10 min at 30-min intervals, ventricular fibrillation (VF) occurred in 30, 35 and 33% of dogs during occlusions 1, 2 and 3, respectively. Magnesium pretreatment reduced the incidence of VF to 14% during occlusion 3 (P less than .05 compared to occlusions without magnesium pretreatment). Neither the prevalence of ventricular ectopic complexes 24 h after MI nor arrhythmia inducibility 4 days after infarction were significantly altered by i.v. magnesium. Magnesium significantly attenuated the ST segment elevation (an index of ischemic injury) and ventricular conduction slowing caused by MI. Because magnesium has been reported to reverse the effects of hyperkalemia, we evaluated the role of this action by infusing potassium directly into a coronary artery (to mimic ischemia-induced hyperkalemia) and administered i.v. magnesium. Potassium infusion markedly slowed intraventricular conduction, an effect fully reversed by discontinuing potassium administration but unaffected by i.v. magnesium. We conclude that magnesium has antiarrhythmic actions only during the early phases of an experimental MI, and that these actions are associated with attenuation of indices of ischemic injury and conduction slowing. These properties of magnesium are similar to those of calcium antagonists, and suggest that magnesium's calcium antagonist properties may be important in its antiarrhythmic actions. PMID- 1941639 TI - [Radioimmunoassay of progesterone in peripheral and placental blood of pregnant rabbits and guinea pigs]. AB - Radioimmunoassay of progesterone in systemic and placental blood of pregnant rabbits and guinea pigs. 1. The level of progesterone in pregnant rabbits and guinea pigs serum was measured directly (without extraction) using a RadioImmunoAssay (RIA). 2. Hormonal concentrations in systemic blood were shown to increase with gestational age, being at their highest half-way through pregnancy (16.03 +/- 2.63 ng/ml for rabbits; 319.01 +/- 42.10 ng/ml for guinea pigs) and decreasing at the end of the pregnancy. 3. Progesterone was not detectable in rabbit placental blood, whereas a high level of this hormone was found in guinea pig placental blood, which increased with gestational age. From the 28th to the 56th post-coital day, the level increased from 143.22 +/- 13.15 to 283.30 +/- 36.84 ng/ml. 4. The method used enables to measure correctly progesterone concentrations in rabbit and guinea pig serum without extraction. PMID- 1941640 TI - Relationship between the spike activities of the small and large intestines. AB - Experiments were performed using chronically implanted electrodes on the dog smooth muscle wall of the stomach and of the small and large intestines. Electrical activity of the muscle wall was recorded before and after feeding. When reaching the terminal ileum the active part of the migrating myoelectrical complex (MMC) continuously induced bursts of spike potentials superimposed on the slow waves. This electrical activity spread to the ascending colon. We also showed the existence of a spike activity on the terminal ileum independent of the MMC (appearing during the phase 1) and propagating to the colon. A relationship between the spike activities of the small and large intestines was also present after feeding. Beside the well-known gastro-colic reflex, we observed an increase in the spike activity of the terminal ileum and ascending colon between the 4th 5th hours after feeding. This probably corresponds to the arrival of the first portions of contents, evacuated from the arrival of the first portions of contents, evacuated from the stomach, and of the last portions of small intestinal contents. In conclusion, there is a relationship between the spike activities of the small and large intestines in starving animals and after feeding, and the terminal ileum plays a substantial role in this relationship. PMID- 1941641 TI - An analysis of calcium effects on diastolic depolarization in sheep cardiac Purkinje fibers. AB - The events by which [Ca]O modifies diastolic depolarization (DD) were analyzed in sheep cardiac Purkinje fibers perfused in vitro. Cs (2 mM) reduced diastolic depolarization (DD) at different [Ca]O and in 10.8 mM [Ca]O revealed an oscillatory potential (VOS) and the decay of a prolonged depolarization (Vex). In the presence of Cs, procedures that reduce Cai (a slower driving rate, lower [Ca]O or tetrodotoxin) abolished VOS and Vex and partially restored DD. In 10.8 mM [Ca]O and at all driving rates, Cs reduced DD slope, DD amplitude and VOS amplitude but had little effect on the VOS time to peak. In 10.8 mM [Ca]O, decreasing calcium overload by different means (2.6 microM TTX, 0.2 mM Cd) abolished VOS and decreased DD slope and amplitude. Substituting Na with Li induced marked aftercontractions but small VOS. In 10.8 mM [Ca]O, Li increased the amplitude of the aftercontractions and decreased that of VOS. Li also depolarized slightly the resting membrane and abolished the voltage undershoot (Emax) at the end of the action potential. In low [K]O, Li repolarized the resting membrane but the repolarization was maintained only in the presence of Ca. It is concluded that Ca overload causes both VOS and Vex which can either be masked by or can mask DD depending on the magnitude of DD and of Ca overload. VOS is apparently caused by an electrogenic Na-Ca exchange since Li-induced Ca overload increases the aftercontraction but decreases VOS. PMID- 1941642 TI - Evidence for the entrainment of breathing by locomotor pattern in human. AB - In human, it has been shown that interactions between locomotor and respiratory patterns may lead to locomotor-respiratory couplings termed entrainment. In order to prove that this coupling is really an entrainment, we tried to show that it obeys one of the expected rules, i.e. that it evolves and is not present for all imposed locomotor frequencies. For that purpose, seventeen healthy volunteers were asked to run on a treadmill at 14 different locomotor rates (instead of 2 or 3 in previous works) for 40 s. All the subjects did not exhibit the same coupling and different relationships could be obtained: the most commonly observed was 2:1 (2 locomotor activities for a respiratory one) but other forms could appear (4:1 and even 5:2 or 3:2). When the coupling evolution was followed in the same subject, it did not appear for all locomotor frequencies but only for locomotor periods close to harmonics of respiratory ones (absolute coordination). On both sides of these values, it progressively evolved to relative coordination and to the lack of coordination. When two forms of absolute coordination were observed in a same subject, the phase relationships followed the rules of the entrainment. Compared to data obtained in quadrupeds, these results suggest that the entrainment of breathing frequency by the locomotor activity is due to central interactions between the respiratory and locomotor pattern generators and does not depend on a chemical regulation avoided here by short locomotor sequences. PMID- 1941643 TI - [Pulvina-lateralis posterior nucleus complex of mammals and the visual function]. AB - It is now well established that the lateral posterior-pulvinar (LP-P) complex of mammals is involved in visual processing. However, the actual function of these large nuclei of the thalamus remains unknown. In contrast to the nearby lateral geniculate nucleus, the LP-P complex does not receive any substantial direct projections from the retina. Its main visual inputs come from the mesencephalon and the neocortex. Most cells in the LP-P complex behave like cortical units. They are tuned to the orientation, direction, spatial and temporal frequencies of the visual stimulus. In addition, most units are binocular and sensitive to relative retinal disparity. Despite their multiple inputs, the LP-P complex cells form an homogeneous population and their overall properties do not reflect those of a given cortical or subcortical area. On the basis of its afferent and efferent connectivity, it has been proposed that the LP-P complex may serve as a relay of an extrageniculate ascendant pathway which originates from the superior colliculus, and/or provide another route for the geniculo-striate input to reach the extrastriate areas. Despite the fact that there is some electro-physiological evidence of such functions, it is now often suggested that the LP-P complex may integrate its multiple inputs and be involved in functions which go beyond those of a simple thalamic relay. Recent findings suggest that the LP-P complex might play a role in visual spatial attention. PMID- 1941644 TI - Adaptive control of functional neuromuscular stimulation-induced knee extension exercise. AB - An automated system for exercising the paralyzed quadriceps muscles of spinal cord injured patients using functional neuromuscular stimulation (FNS) has been developed. It induces smooth concentric and eccentric contractions in both limbs to enable bilateral 70 degree knee extensions in an asynchronous pattern. External load resistance is applied at the ankle level to "overload" the muscles and bring about training effects. The system uses adaptive control methods to adjust FNS current output (threshold level and the ramp slope) to the quadriceps muscles to maintain performance as the muscles fatigue. Feedback control signals for limb movement and knee extension angle are used to continuously adjust the FNS current parameters so that the external load is moved through the preset zero to 70 degree angle range. Typically, the threshold current level and the FNS current increase as the muscles fatigue to maintain performance with repetitive contractions. Fatigue is defined as the inability to extend the knee to 50 percent of the 70 degree target angle. When this occurs, FNS is automatically terminated for the fatigued leg, while the functioning leg continues to exercise. The automated nature of this system appears to be advantageous as compared to a manually operated system for subject safety, convenience, and uniformity of exercise bouts. Simulated safety problems, such as hyperextension of the knee joint, open circuitry, muscle spasms, and low battery power, were successfully detected by the logic circuitry, and the system followed appropriate safety procedures to minimize risk. PMID- 1941645 TI - Musculoskeletal responses of spinal cord injured individuals to functional neuromuscular stimulation-induced knee extension exercise training. AB - This study was conducted to evaluate a newly designed functional neuromuscular stimulation (FNS)-induced knee extension (KE) exercise system that incorporates the most desired features of previously described systems by determining the musculoskeletal responses of spinal cord injured (SCI) individuals to training. A specially designed chair and electrical stimulator were fabricated for FNS induced KE resistance exercise. Surface electrodes were placed over motor points of the quadriceps muscles, and KE was alternated between legs at an average rate of 6 KE/min/leg. KE testing protocols were developed for pre- and post-training evaluations of performance, and 12 SCI subjects exercise-trained up to three times per week for 36 sessions using a progressive resistance load at ankle level. Pre- and post-training evaluation data were statistically compared using a 0.05 level for significance. Quadriceps muscle performance (strength x repetitions) improved for both legs in all subjects as indicated by significant increases in load resistance and repetitions over the 36-session training period (right leg mean = 1156.0 versus 1624.8 kg.reps, left leg mean = 1127.3 versus 1721.1 kg.reps). In addition, knee range of motion significantly increased (right leg mean = 134 versus 146 degrees, left leg mean = 133 versus 144 degrees). Thigh skinfold, thigh girth, body weight and bone density were not significantly changed. The lack of decrease in bone density in some subjects suggests that the training may retard the rate of bone loss which typically occurs with SCI. No injuries or problems were encountered during testing and training.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941646 TI - Erythema and skin temperature following continuous sitting in spinal cord injured individuals. AB - Pressure sores are a severe and costly problem for many disabled individuals. There is a need for quantitative tools to assess damage produced by external loads on human skin and underlying tissues. Clinically, intensity and size of skin erythema have been used as indicators of tissue damage. Temperature is a quantifiable measure, and various studies have investigated the thermal response to localized pressure. The purpose of this study was to measure the effect of "long-term sitting" on skin temperature and erythema, in a situation that closely approximated what a spinal cord injured individual encounters on a regular basis. The resulting data indicated that: 1) a consistent skin temperature pattern occurred after pressure relief from the seated position; 2) skin temperature of experimentally-induced erythematous areas often remained elevated, even after one hour of pressure relief; and, 3) a qualitative, but not quantitative, correlation exists between erythema size and intensity and skin temperature. Implications of this research include the potential use of temperature to: 1) monitor the effectiveness of various strategies being used to prevent the development of pressure sores; and, 2) predict incipient tissue damage. PMID- 1941647 TI - Thirty-minute continuous sitting force measurements with different support surfaces in the spinal cord injured and able-bodied. AB - Able-bodied, paraplegic, and quadriplegic subjects sat for 30-minute intervals on various surfaces in a wheelchair with a forceplate mounted on the seat in order to determine factors that could contribute to the formation of decubitus ulcers. All three groups of subjects sat on ROHO and Jay cushions; in addition to sitting on the two cushions, the able-bodied subjects sat on a hard surface. Factors studied were: normal and shear seat forces, the location of the center of mass, and armrest force. The forceplate was under the cushions; therefore, the values reflect average forces over the buttocks and posterior thighs. These factors were compared between disability levels as well as between surface types. Larger, normal, and forward shear forces and a more anterior position of the center of mass were observed with the ROHO cushion. More frequent and larger lateral weight shifts occurred with the Jay cushion. The armrests tended to support from 5 percent of the body weight for quadriplegics to 9 percent for paraplegics. The results suggest that armrests reduce seat forces by carrying some of the body weight. PMID- 1941648 TI - An interactive computer graphics system for the design of molded and orthopedic shoe lasts. AB - The Department of Computer Science at North Carolina State University, with support from the Department of Veterans Affairs and National Aeronautics and Space Administration (NASA) Langley Research Center, has developed an interactive graphics program for the development of shoe lasts from digitized images of feet or digitized images of commercial shoe lasts. The program runs on a Sun 3/260 computer with a TAAC-1 graphics accelerator. The program contains operations for region addition and deletion, techniques for narrowing the ankle area, methods for toe extension, operations to allow for shoe inserts, etc. Once the operations by the user are complete, the program will resample the resulting last in a 512 x 512 array. The user is then allowed to select an error tolerance which will guide a data reduction program to represent the last as Coons patches. These patches are then transmitted to a milling machine which will cut the last. PMID- 1941649 TI - Walking reeducation with partial relief of body weight in rehabilitation of patients with locomotor disabilities. AB - This study was undertaken to investigate the contribution of a weight-relieving system on the gait of patients with severe locomotor disabilities. Temporal parameters of gait and subjective evaluations of the effect of the system were studied in 24 patients and 6 healthy subjects. Partial weight relief was accomplished through a pneumatic system mounted in the ceiling over a conductive walkway which was placed between parallel bars. Subjects were tested in three walking trials: free walking, walking while harnessed to the system but without weight relief, and walking with relief of 20 percent of their body weight. Temporal measurements indicated a positive effect of the system on duration of the stance and swing phases. The percentage of the stance period of the involved lower limb relative to the uninvolved one increased by 148 percent; at the same time, the swing period of the involved limb relative to the sound one decreased to 68 percent of that value in free ambulation. A substantial increase in gait symmetry and velocity were also noted. Subjective information from the patients and observers also pointed to a facilitative effect of the system on the patients' ambulation. Conversely, natural gait velocity of the healthy subjects was impeded by weight relief through the system. PMID- 1941651 TI - Rehabilitation literature. PMID- 1941650 TI - A method of assessing the efficacy of memory rehabilitation techniques using a "real-world" memory task: learning a computer language. AB - A software program developed to assess the effectiveness of memory rehabilitation techniques is described. This project addresses current weaknesses in the research literature on memory rehabilitation: 1) remediation strategies are evaluated in terms of performance on a practical, real-world memory task, rather than a laboratory learning task; 2) the program allows maximum flexibility in assessing a wide variety of remediation strategies and training schedules; and, 3) the software, which provides sensitive outcome measures and detailed feedback about performance, is adaptable to the needs of patients with widely varying degrees of memory impairment. The results of a demonstration project are included to illustrate the use of this technology in determining the usefulness of different mnemonic strategies for patients with specific patterns of memory deficit. The importance of assessing maintenance of rehabilitation training over time is stressed. PMID- 1941652 TI - Acute hemodynamic responses of spinal cord injured individuals to functional neuromuscular stimulation-induced knee extension exercise. AB - The purpose of this study was to determine and compare acute hemodynamic responses of spinal cord injured (SCI) quadriplegics (quads), and paraplegics (paras) during a graded-intensity knee extension (KE) exercise test utilizing functional neuromuscular stimulation (FNS) of paralyzed quadriceps muscles. Seven quads and seven paras (N = 14) performed a series of 4-minute stages of bilateral alternating FNS-KE exercise (approximately zero to 70 degree range of motion at the knee and 6 KE/min/leg) at ankle loads of 0, 5, 10, and 15 kg/leg. Physiologic responses were determined with open-circuit spirometry, impedance cardiography, and auscultation. Comparing rest with peak FNS-KE for both groups combined, FNS KE exercise elicited significant (p less than 0.05) increases in oxygen uptake (130 percent), pulmonary ventilation (120 percent), respiratory exchange ratio (37 percent), arteriovenous oxygen difference (57 percent), cardiac output (32 percent), stroke volume (41 percent), mean arterial pressure (18 percent), and rate-pressure product (23 percent). Heart rate increased significantly by 11 percent from the 5- to the 15-kg/leg stages. Physiologic responses of quads and paras were very similar, except for lower (p less than 0.05) arterial pressures, rate-pressure product, and peripheral vascular resistance in quads. This graded FNS-KE exercise up to the 15-kg/leg load induced relatively small but appropriate increases in aerobic metabolism and cardiopulmonary responses that appear to be safe and easily tolerated by quads and paras. Arterial pressure needs to be monitored carefully in quads to prevent excessive hypertension or hypotension. Although FNS-KE exercise has been shown to elicit peripheral adaptations to improve muscle strength and endurance, it is probably not an effective central cardiovascular training tool for all but the least fit SCI individuals. This information is important for understanding the effects of FNS use during more complex activities such as cycling and ambulation. PMID- 1941653 TI - Aberrant glycosylation in oral malignant and premalignant lesions. AB - Cell surface carbohydrates serve as differentiation and developmental markers characteristic of different cell and tissue types. The expression of these carbohydrate antigens is often significantly altered in tumors, particularly in those arising from epithelial tissues. Analysis of cell surface carbohydrates in oral epithelium have shown that in normal epithelium they are expressed in a way that shorter carbohydrates are found on basal cells and that these carbohydrate structures are elongated parallel to terminal differentiation. The carbohydrate expression is altered in oral carcinomas and in some oral premalignant lesions. The change in carbohydrate expression can at present be explained by the lack of synthesis of specific glycosyltransferases. We have found mosaicism in the expression of carbohydrate antigens in all tumors and have found that the expression of a specific carbohydrate in the deep invasive parts of the tumor correlates with tumor prognosis. PMID- 1941654 TI - Adult and infantile myofibromatosis: a report of three cases affecting the oral cavity. AB - Myofibromatosis is a rare but well recognized entity which was originally thought to affect only neonates and infants. It is now apparent however that adults may also be affected. Solitary cases affecting the oral cavity appear to be rare and only two cases of solitary lesions in adults appear in the literature. This report documents three solitary cases; two typical lesions in infants and a lesion from the tongue of an adult. The lesions were composed of small polygonal cells and large elongated cells in a scant fibrous stroma. The elongated spindle cells were identified as myofibroblasts by immunocytochemistry and electron microscopy. The lesions showed characteristic features which enabled them to be distinguished from other fibrous lesions and from benign or malignant smooth muscle tumors with which they have frequently been confused. PMID- 1941655 TI - Effects of gamma radiation on incisor development of the prenatal albino mouse. AB - Fetuses of pregnant albino mouse exposed to 400 rad of gamma-irradiation, on the 12th gestational day, were compared with unirradiated fetuses to asses the radiation effect on developing incisors. Pregnant animals were sacrificed on day 18 post coitum, and their fetuses were decapitated. Heads were routinely prepared, frontally sectioned, and stained with hematoxylin and eosin. Histologic examination demonstrated that the development of the maxillary and mandibular incisors was retarded in all the experimental fetuses and were in early bell stage, whereas those of the control animals were elaborated their matrices. It was concluded that gamma-irradiation interferes with cytodifferentiation of the enamel organ and dental papilla and subsequently inhibits normal odontogenesis. PMID- 1941656 TI - Recurrent aphthous ulceration: vitamin B1, B2 and B6 status and response to replacement therapy. AB - An evaluation of the thiamine, riboflavin and pyridoxine (vitamin B1, B2 and B6) status of 60 patients with recurrent mouth ulcers was performed. Seventeen patients (28.2%) were found to be deficient in one or more of these vitamins. Replacement therapy of these vitamins was given to a study group of deficient patients and a non-deficient group for one month. At the end of therapy and after a follow-up period of 3 months, only those patients who had a B complex deficiency had a significant sustained clinical improvement in their mouth ulcers. Vitamin B1, B2 and B6 deficiencies should, therefore, be considered as another possible precipitating factor in recurrent aphthous ulceration. PMID- 1941657 TI - Recurrent aphthous stomatitis. A study of the clinical characteristics of lesions in 93 cases. AB - We studied the clinical characteristics of 93 patients with recurrent aphthous stomatitis (RAS); 66 corresponded to minor aphthae (MiRAS), 20 to major aphthae (MaRAS), and 7 to herpes-like ulcerations (HU). MiRAS was seen to present the lowest rate of recurrences, as well as the shortest duration and the fewest lesions per episode. In turn, MaRAS presented the longest duration per recurrence, along with a number of lesions and recurrences that was lower than in HU but greater than in cases of MiRAS. Finally, HU developed the greatest number of lesions and recurrences. When we classified RAS according to the rate of episodes, no statistically significant differences were observed among the three types in terms of patient age, number and duration of lesions, or evolution time of the oral disorder. PMID- 1941658 TI - The person behind the eponym: Burrill B. Crohn (1884-1983). PMID- 1941659 TI - [A method for measuring the amount of retrogradely transported HRP in the rat masseteric motoneuron using Mesulam's HRP histochemical protocol and an image processing system. An investigation of the effect of dopamine receptor antagonists on the retrograde transport of HRP]. AB - We developed a method for a determination of the amount of retrogradely transported HRP in the rat masseteric motoneuron using a modification of Mesulam's HRP histochemical protocol and an image processing system combined with a light microscope and a television camera. To test the validity and reproducibility of the new method, a quantitative comparison of the amount of dark blue granules of HRP-product in the cell body of masseteric motor neurons was performed between the right and left trigeminal motor nuclei of 70 rats, which resulted in no significant difference. An additional study used the method was made of the effects of administration of five dopamine receptor antagonists with different biochemical and pharmacologic properties on retrograde transport of HRP in the rat masseteric motoneuron. As a result, chlorpromazine, haloperidol, SCH 23390, and sulpiride significantly enhanced retrograde transport of HRP as against domperidone which showed no significant change in the transport. A possible regulatory system for retrograde transport of HRP in the masseteric motoneuron was discussed in relation to the action of the dopamine receptor. PMID- 1941660 TI - [Fibrinolytic enzymes extracted from the earthworm. Lumbricus rubellus: a possible thrombolytic agent]. PMID- 1941661 TI - Combination natural tooth and implant-borne removable partial denture: a clinical report. PMID- 1941663 TI - Effects of laboratory disinfecting agents on color stability of denture acrylic resins. AB - This study determined the effects of chemical disinfecting agents on denture acrylic resins. Tested resins included the products CH Lucitone, Triad VLC, and Truliner. The disinfecting agents were sodium hypochlorite, Exspor, Cidex, and Wescodyne-D. Acrylic resin samples were placed in the various disinfecting agents and then evaluated for color changes at time intervals ranging from 15 minutes to 72 hours. No observable color change of any acrylic resin was seen before 2 hours. Both 1% sodium hypochlorite and 2% Cidex disinfectants produced the least discoloration of the acrylic resins, and Wescodyne-D disinfectant produced the most acrylic resin discoloration. Truliner resin discolored more than Triad VLC resin, and both underwent more color change than CH Lucitone resin. If manufacturers' recommended disinfecting times are followed, clinical and laboratory disinfection of acrylic resin dentures should cause no observable color change. PMID- 1941662 TI - Surface preparations for metal frameworks of composite resin veneered prostheses made with an adhesive opaque resin. AB - Bond strengths of a laboratory developed light-cured composite resin to dental casting alloys were evaluated with a new adhesive opaque resin. The metal specimens were type III gold, nickel-chromium, and cobalt-chromium alloys, while the surface treatments for bonding were heating, Sn plating, and ion coating. The cast metal specimens were "particle blasted" with aluminum oxide and were surface treated. Adhesive 4-META/MMA-TBB opaque resin was applied and a light-cured composite resin was placed over the opaque layer. The prepared specimens were thermocycled in water and shear bond strengths were recorded. The light-cured composite resin was bonded strongly to heated or Sn-plated type III alloy with 4 META/MMA-TBB opaque resin. Copper ion coating in a sputter coater was effective for all three alloys, with only slightly diminished bond strengths. These methods were satisfactory for making composite resin veneered prostheses. PMID- 1941664 TI - Fabrication of one-piece hollow obturators. AB - This technique is a controlled process in which the thickness of the obturator can be easily modified by adding to or shaving off the dimensionally stable silicone putty. All phases of the obturator fabrication are heat-cured and not autopolymerized, thus negating the disadvantages of other techniques. The technique provides more predictable results in obturator fabrication as it uses silicone putty as the obturating material as opposed to sugar, asbestos, or other silicone rubber foams that can be messy, dangerous, and unstable. This technique can also be used for patients with atrophic maxillae where the hollow denture can significantly reduce the weight of the restoration. PMID- 1941665 TI - Expedient and effective interim restorations for compromised posterior teeth. PMID- 1941666 TI - A technique for accuracy with occlusal registration and adjustments. PMID- 1941667 TI - Stress distribution surrounding endodontic posts. PMID- 1941668 TI - Clinical evaluation of three occlusal registration methods for guided closure contacts. AB - This clinical study compared two occlusal registration methods (Occlusal Indicator Wax and Accufilm) with the T-Scan system for the identification of guided closure contacts. The patients were divided into two groups according to the centric relation-maximum intercuspation (CR-MIP) discrepancy and comparisons of guided closure contacts were performed with the paired methods. Wax and Accufilm materials were significantly different in their agreement on guided closure contacts. The T-Scan system demonstrated less of a disparity with both methods but more closely resembled the Occlusal Indicator Wax material. The CR MIP slide also significantly affected the agreement between methods during identification of guided closure contacts. PMID- 1941669 TI - Microleakage of composite resin cores treated with various dentin bonding systems. AB - Composite resin post and cores have gained widespread acceptance as an alternative for cast-gold post and core systems. A prefabricated metal post is generally used. Substantial microleakage at the interface between the composite resin core and the dentin substrate may occur. A tight and impervious bond between the dentin and the restorative material is critical for the longevity of core restorations. This study compared the microleakage of composite resin cores treated with various dentin bonding agents, including the recently developed Gluma, Tenure, and Scotchbond 2. The results indicated that Tenure and Scotchbond 2 bonding agents were most effective in reducing microleakage, followed by Gluma and conventional Scotchbond (Dual Cure) bonding agents. Although all proprietary dentin bonding systems used in this study significantly reduced microleakage, no system was capable of preventing microleakage completely. PMID- 1941670 TI - Supraeruption of the unopposed maxillary first molar. AB - Supraeruption of the maxillary first molar in the absence of the mandibular first molar was observed in subjects with both normal and pathologic periodontics. Both the migration of the gingival margin and the increase in the crown height were evaluated in terms of the length of time the antagonist tooth had been missing. Values obtained were compared with those of a reference group with complete normal dentitions. The results show that in the first years following the loss of the opposing tooth, supraeruption is mainly due to growth of the periodontium. Later or in the case of periodontal pathosis, tooth movement beyond the occlusal plane is due principally to active eruption. PMID- 1941671 TI - A crown for clinically investigating microleakage. AB - This investigation evaluated a cast crown with an access port for in vivo microleakage studies. Fifteen complete cast crowns containing an access port in the facial surface were cast. The gingival margins of the crowns were modified to test the sealing ability of the access port. Each casting was thermocycled 750 times at 5 degrees to 60 degrees C over a 24-hour period. Air pressure of 90 psi followed by 28 mm Hg vacuum was applied for 1 hour each during immersion of the devices in silver nitrate solution. Castings were embedded in acrylic resin and sectioned with a diamond saw through the sealing device. Scanning electron microscopy and energy dispersive spectroscopy analysis revealed no leakage with the 13 test devices and 100% leakage with the controls. The device should be effective for use in human subjects. PMID- 1941672 TI - Positional accuracy of four die tray systems. AB - This study evaluated the positional accuracy of dies with four die tray systems. The die trays were: (1) Accu*trac Precision die system, (2) Model-Tray system, (3) Sterdo Split model tray, and (4) Tricodent One*Cast die tray system. Positional change of the dies was measured by using an Olympus binocular scanning tunneling microscope (STM). Positional change of the dies was the difference between preremoval and postremoval die position. Results show that all four die tray systems are not significantly different in most measurement categories, although the Model-Tray system was significantly different from the other die tray systems in one measurement category. PMID- 1941673 TI - Effects of lubrication on the retention of tapered and parallel cast post and cores. AB - The effects of lubrication on the retention of parallel-sided and tapered cast post and cores cemented with zinc phosphate-cement (ZnPO4) and glass ionomer cements were investigated. Seventy-two maxillary canine teeth of similar size were selected for direct, parallel-sided post and core castings. The canines were sectioned at the cementoenamel junction and mounted in resin blocks. A post space was prepared to 1.5 mm (d) x 10 mm (I) with a handpiece mounted in a surveyor. The teeth were divided into four groups: ZnPO4 without lubricant, ZnPO4 with lubricant rinsed with water, ZnPO4 with lubricant removed by solvent, and ZnPO4 with solvent alone. The same four groups were made by using glass ionomer cement. Retention was tested with a 4200 series Instron machine by pulling the castings out of the teeth. There were no significant differences in retention among the eight groups of parallel posts at alpha = 0.05. The testing procedure was repeated by using an 11 mm post with 6 degrees of taper. With tapered posts, a statistically significant reduction in retention was found in the lubricated samples when compared to the nonlubricated samples. PMID- 1941674 TI - The effect of powder/liquid ratio on the in vivo solubility of polycarboxylate cement. AB - A clinical study of the solubility of three powder/liquid ratios of polycarboxylate cement demonstrated a threefold increase in the solubility for the lower powder/liquid ratios. The three liquid/powder ratios tested were within the range recommended by the manufacturer. The data suggest that the higher powder/liquid ratio (1.5:1) is preferable when minimal solubility is a primary requirement. PMID- 1941675 TI - Resin-bonded etched castings with extracoronal attachments for removable partial dentures. AB - An innovative method of using resin-bonded etched cast extracoronal attachments as an esthetic alternative in removable prosthodontics is presented. The technique is simple, conservative, inexpensive, and not time-consuming. The steps of abutment teeth preparation, casting of a precise framework, and cementation are technique-sensitive, and short cuts are not well tolerated. The existing clinical results indicate that the technique is a valuable adjunct in the field of esthetic removable partial prosthodontics. PMID- 1941676 TI - Measurement of oral status and treatment need among subjects with dental prostheses: are the measures less reliable than the prostheses? Part III: Fixed prosthodontics and restorative dentistry. AB - Poor quality measures of oral status and treatment need have adversely affected clinical and epidemiologic research in prosthodontics. The failure to create reliable and valid indices prevents comparing and pooling data from different studies and obscures meaningful variation within individual studies. Part III of this literature review is focused on problems of measurement of restoration quality and need for treatment in the areas of fixed prosthodontics and restorative dentistry. PMID- 1941677 TI - Osseointegrated implant-supported and magnetically retained ear prosthesis: a clinical report. AB - Osseointegrated implants were placed in the temporal bone and were used to retain attachments for an ear prosthesis. A screw-retained magnetic alloy casting was used to retain an acrylic resin magnet keeper, to which a silicone ear prosthesis was attached. The keeper provided vertical support for the prosthesis and facilitated orientation for prosthesis insertion. Stability and retention were provided without the use of adhesives. PMID- 1941678 TI - Simplified technique for the fabrication of a hollow obturator prosthesis using vinyl polysiloxane. AB - A technique in the fabrication of a heat-cured acrylic resin transitional maxillary obturator using vinyl polysiloxane putty instead of wax is demonstrated. The putty allows a decrease in the time of fabrication in both the pattern and the processing stage of the prosthesis. PMID- 1941679 TI - Fluoroscopy and nasoendoscopy in designing palatal lift prostheses. AB - Prosthodontists frequently provide prostheses for the management of speech disorders related to palatopharyngeal dysfunction. Optimal prosthetic management of the palatopharyngeal port requires close interaction between the prosthodontist and speech pathologist in the use of videofluoroscopy and videonasoendoscopy for design, placement, and modification of the prosthesis. Function of the palatopharyngeal port during production of controlled samples of connected speech can be observed from multiview fluoroscopy, including lateral and frontal projections. Like fluoroscopy, nasoendoscopy can be used to observe and record function of the palatopharyngeal port during speech. This article provides an overview of the procedures suggested for diagnosing palatopharyngeal disorders. A method for designing and placing a prosthesis to aid in obturating the nasopharynx is also suggested. PMID- 1941680 TI - Multidisciplinary approach to the differential diagnosis of facial, head and neck pain. AB - Pain in the region of the head and neck is one of the most common complaints that bring patients to the dentist. Because of the complexity of the anatomy as well as the vagueness of presenting symptoms, head and neck pain often is a diagnostic problem. Many different specialists may ultimately be consulted to make a comprehensive diagnosis and institute effective therapy. It is up to the one who coordinates the diagnostic sequence to have an understanding of the various pathologic conditions that can be manifested as pain in the head and neck. Although a comprehensive knowledge of all disciplines is not necessary, an overall understanding of the various disciplines of medicine as they relate to head and neck pain is valuable. The primary provider should establish a group of specialists to whom patients can be referred for further diagnosis and treatment when necessary to provide optimum care. PMID- 1941681 TI - Hyoid bone syndrome: a degenerative injury of the middle pharyngeal constrictor muscle with photomicroscopic evidence of insertion tendinosis. AB - This article describes the condition known as hyoid bone syndrome, its diagnosis by exclusion, and the histopathologic evidence of focal, degenerative muscle injury. The injury involves the origin fibers of the middle pharyngeal constrictor muscle on the greater cornu of the hyoid bone. The importance of the dentist and physician in recognizing the condition is emphasized, because dental and nondental pain reference sites make up the syndrome. PMID- 1941682 TI - Report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry. AB - Subjects of the past decade in the dental literature are reflected in this year's Committee report. We note the decrease in the prevalence of caries, the influence of dental implants, the advancements in dental materials, and the continued efforts to control adhesive events in the oral cavity. This year we included comments from and about many significant review articles published this past year. The Committee continues to be concerned about the quality of some of the work reported and the quality of the reporting. We have attempted to select the distinguished work, that which provides new information to our profession. The subjects covered include pulp biology, caries prevention, periodontics, implants, craniomandibular function and dysfunction, occlusion, and dental materials. PMID- 1941683 TI - Formalin (0.25%) as topical anti-microbial agent in burns. AB - In a prospective controlled trial, 0.25% formalin spray was compared with 2% silver sulfadiazine cream as the local treatment of burns. Formation and separation of eschar, infection and death rates were recorded. In the group receiving formalin, rates of formation and separation of eschar were significantly more (P less than 0.001 and P less than 0.05 resp.) compared to other group. Infection rate and fatality due to infection were also reduced. Other advantages of formalin are ease of application and the low east. PMID- 1941684 TI - Microbiological study of breast milk with special reference to its storage in milk bank. AB - Sixty five breast milk samples were subjected to bacteriological studies; each sample thrice (in fresh state, after heating at 1000C and freezing for 5 days at 20 degrees C). In fresh State, Staphylococci and diphtheroids were predominant organisms. After heating, none of the samples showed any micro-organisms while after freezing for 5 days, all the samples showing presence of micro-organisms earlier, showed decrease in colony counts. None of the milk samples showed inclusions of cytomegalovirus. Serum samples of mothers tested for Hepatitis B surface antigen and human immunodeficiency virus antibodies gave negative results. Such studies i.e. screening of breast milk samples are important if human milk is to be stored in banks and supplied to premature (high risk group) children. PMID- 1941685 TI - Ectopic pregnancy after tubal sterilization. AB - We report 13 cases of ectopic pregnancy following tubal ligation out of 287 ectopic pregnancies seen during a six year period (1984-1989). These findings suggest that tubal sterilization does not invariably confer infertility. Ectopic pregnancy must not be disregarded in women who have undergone tubal ligation, especially if two or more years have elapsed since the sterilization. PMID- 1941686 TI - Urological injuries during obstetric and gynaecological surgical procedures. AB - Urological injuries during obstetric and gynaecological operations carried out between Jan. '88 to Dec. '88, at a hospital involved in resident teaching programmes were analysed retrospectively. Each case was reviewed for predisposing factors, location and type of injury, time and method of recognition and management. Fifteen injuries were documented in 892 gynaecological procedures and 296 obstetric procedures. Twelve injuries occurred during gynaecological operations whereas 3 occurred during obstetric operations. Thirteen were bladder injuries and two were ureteric injuries. Infiltrating carcinoma of cervix, pelvic adhesions, adhesions because of previous operations and distorted anatomy, were the important risk factors. PMID- 1941687 TI - Tuberculosis of breast (study of 7 cases). AB - Seven cases of tuberculosis of breast are presented. The clinical features were multiple discharging sinuses, lump, ulcer and recurring abscess of breast. Diagnosis relied on histological appearance. Acid fast bacilli being present in only one specimen and positive culture obtained in one patient. Successful treatment combines antituberculous drug therapy with removal of infected breast tissue. PMID- 1941688 TI - Functional endoscopic sinus surgery--I (Anatomy, diagnosis, evaluation and technique). AB - It has been proved beyond doubt that the causation and perpetuation of disease in the dependent sinuses (maxillary and frontal sinuses) is secondary to disease of the ostiomeatal complex, the primary focus of which is the anterior ethmoid. Based on this concept, functional endoscopic sinus surgery (FESS) aims at correcting the underlying pathology in the ethmoids and helps to re-establish normal ventilation and mucociliary clearance of the dependent sinuses. PMID- 1941689 TI - Functional endoscopic sinus surgery--II (A preliminary study). AB - Seventy-eight patients of chronic sinusitis were subjected to functional endoscopic sinus surgery by the technique described in the previous paper. The clinical features, findings at surgery and the results of this technique are described here. PMID- 1941690 TI - The value of ultrasonography in the diagnosis of adnexal masses. AB - Seventy patients with palpable adnexal masses were subjected to ultrasonographic examination. Three patients with negative ultrasound and no disease were excluded from the final analysis. Correct diagnosis was obtained in 58.2% patients; contributory information in 16.4%. Ultrasonography is valuable in diagnosing functional and benign ovarian neoplasms. It is also useful in suspecting malignant ovarian neoplasms and confirming diagnosis of ectopic pregnancy, if correlated with the clinical findings. PMID- 1941691 TI - Difficult intubation--when can we predict it? AB - Anaesthetists at times encounter difficult intubation in an apparently normal individual in spite of using the best possible positioning and most profound relaxation. This study was carried out to find out the most simple and easy measurement that may predict a difficult intubation. The study was conducted in three groups of patients of twenty each. The first group consisted of patients in whom intubation was easy. Second group consisted of anticipated difficult intubation. Cases in whom very difficult intubation was encountered were analyzed retrospectively and were included in third group. An attempt has been made to predict difficult intubation with the roentgenographic study of lateral view of mandible along with the measurement of distance from chin to thyroid cartilage. Of all the parameters, ratio of effective mandibular length to posterior mandibular depth and distance from chin to thyroid cartilage were found to be important to predict difficult intubation. PMID- 1941692 TI - Detection of autoantibodies against 3,5,3'-triiodothyronine in a hyperthyroid patient (a case report). AB - A 35-year-old female patient was evaluated for thyroid function and was found to be hyperthyroid clinically and by laboratory tests. During the course of treatment with neomercazole, she developed a bizarre picture with consistently low T3 levels irrespective of her clinical thyroid status and other laboratory tests like serum T4 and TSH levels. The serum of the patient when analysed for the presence of autoantibodies was positive for those against T3. The presence of T3 autoantibodies was confirmed by other laboratory techniques like assessment of blank values in radioimmunoassay, binding of T3-125I to isolated gamma globulin and starch gel electrophoresis. Autoantibodies were found to be present only against T3 and not against. T4 The affinity constant of T3 antibodies was 4 x 10(9) lit. mol-1 as determined by Scatchard plot analysis while total binding capacity was 23 x 10(-11) mol/L. PMID- 1941693 TI - Ultrasound guided cephalocentesis (USGC) (report of 2 cases). PMID- 1941694 TI - Antipyrine and doxycycline pharmacokinetics in patients with thyroid disorders. AB - Pathological conditions are known to affect pharmacokinetics of many drugs. Antipyrine half-life is used as a marker of liver microsomal enzyme function. Antipyrine pharmacokinetics, therefore, was investigated in 23 thyrotoxic and 11 euthyroid goitre patients. Of these, 11 thyrotoxic and 9 euthyroid goitre patients also participated in doxycycline bioavailability studies. In thyrotoxic patients, antipyrine half-life and AUCo infinity and doxycycline Cpmax and AUCo infinity were found to be reduced as compared to those of healthy euthyroid normal subjects. Following treatment of thyrotoxicosis, the antipyrine half-life and AUCo infinity returned to normal. Doxycycline AUCo infinity returned to near normal range but Cpmax did not. PMID- 1941695 TI - Iniencephaly with cyclopis (a case report). AB - Iniencephaly is a rare neural tube defect. We report a rare association of iniencephaly with cyclopia, probably the third such report in the literature. PMID- 1941696 TI - Annular pancreas in adults (2 case reports). AB - Two cases of annular pancreas in adults are being reported. In the first case, a middle aged lady presented with duodenal obstruction and gastric ulcer. Anterior H. S. V. with posterior truncal vagotomy and isoperistaltic duodeno-jejunostomy relieved her symptoms. In the second case, a young girl presented with duodenal obstruction, severe wasting and gross dehydration. She had an uneventful recovery following a duodeno-jejunostomy. PMID- 1941697 TI - Vagal paraganglioma (2 case reports). AB - Paragangliomas are rare tumours of the head and neck and are a diagnostic challenge. Two cases of paragangliomas arising from the vagus are being reported. In the first case, an angiogram raised the possibility of intravagal tumour and exploration followed by biopsy confirmed the diagnosis. In the second case, it was a diagnostic surprise where exploration was done on a clinical suspicion of parotid swelling and on the table, the swelling was found to arise from the vagus nerve pushing the parotid gland laterally. PMID- 1941698 TI - Congenital intermittent atrio-ventricular dissociation in tetralogy of Fallot (a case report). AB - A case of tetralogy of fallot with congenital intermittent atrioventricular dissociation is reported. A review of standard postgraduate books of cardiology fails to describe this condition, thus showing its extreme rarity. The therapeutic dilemma in treating such a case is also discussed. PMID- 1941699 TI - Actinomycotic pseudo-tumour of the mid-cervical region (a case report). AB - Cervicofacial actinomycosis is today a rare disease in our country. Isolated actinomycotic neck masses are extremely rare. A case of young man with an isolated midcervical tumour like actinomycotic granuloma without sinuses or discharging granules is reported here. PMID- 1941700 TI - Methyl alcohol poisoning: an autopsy study of 28 cases. AB - Twenty eight fatal cases out of the 97 cases of methyl alcohol (MA) poisoning admitted to K. E. M. Hospital in August 1988 during a single outbreak were studied. The latent period between consumption of the drink and development of symptoms was variable (range 7 1/2 hours to 60 hours). CNS symptoms were predominant (75% of cases) and shock either at admission or as a late event was seen in 89% of the cases. Blurring of vision was seen in 42.8% and blindness in 10.7% of cases. Minimum fatal period was 7 1/2 hours and maximum was 12 days. Methanol levels in blood and viscera were variable (average 155.8 mg%, max. 420.4 mg%). In 4 cases, significant amount of MA was detected in stomach contents 5-12 days after consumption of MA, raising the question of resecretion of MA in stomach. Shrinkage and degeneration of neurons in the parietal cortex was seen in 85.7% of cases. Putamental degeneration and necrosis was seen in 7.14%. Haemorrhage (3.5%) and sponginess (7.14%) was observed in the optic chiasma. Severe renal tubular degeneration and patchy necrosis was seen in all cases. Fatty changes (67.8%) and microvesicular fat (42.5%) were seen in the hepatocytes. PMID- 1941701 TI - [Evaluation studies of experimental carcinogenesis]. AB - In many cases, epidemiological studies demonstrate carcinogenic risk of occupational exposures and industrial processes, but do not allow to assess carcinogenic potential of the various substances involved in exposures (speciation). Expert judgment combining human and animal data is needed for classifying and labelling of the pure substances. For decision aiding purpose, a method was established for reviewing critically experimental carcinogenesis: 1. Standardized toxicological profiles are established according to pure substances, species, strains and administration routes. 2. Methodological evaluation is made using a scheme based on 3 critical parameters: study duration which should extend to the life expectancy of the species under study; sample size, the statistical significance of negative experiments being ascertained depending on size of samples; survival rates of groups, since sufficient numbers of animals should be at risk during most of their life span. 3. Classification of the results for risk assessment, taking into account the relevance of the administration routes. PMID- 1941702 TI - [Unusual cardiac rhythm disorder induced by clomipramine ingestion]. AB - The authors relate a case of atrioventricular block supplied by junctional rhythm and without blood pressure alteration during a clomipramine poisoning. This electrocardiographic change is unusual and systematic electrocardiography during hospitalization is an absolute necessity. PMID- 1941703 TI - [Alveolar paraffinosis. (Apropos of an inhalation pneumopathy resistant to antibiotics in an aged woman)]. AB - Case report of an exogenous lipoid pneumonitis fortuitously discovered during acute barbituric intoxication. Discussion about pathogenicity of paraffin oil. PMID- 1941704 TI - [Neurocomportmental disorders in an urban population exposed to lead]. AB - A study was performed in 278 people living in a Mexican town with a high lead environmental pollution. Lead blood level was found very high (m:59.7 micrograms/l) and some abnormalities were also found for free erythrocyte Protoporphyrin and ALA dehydratase. A significant dose-response relationship was also found with somatic complaints like loss of appetite, insomnia and headache. PMID- 1941705 TI - [Manganese impregnation in miners of the Ogooue Mining Company at Moanda (Gabon)]. AB - Analyses on manganese noxiousness have been carried out various working stations of Moanda. The men who are most exposed work in the grinding and packing posts. In the occupational surroundings we have rates of 146.42 mg/m3 of manganese while in the blood the values turn around 2.310 micrograms/l. PMID- 1941706 TI - [Acute poisoning by scilliroside]. AB - A 43-year-old man, with no history of cardiac disease, deliberately ingested 4 tablets of a rodenticide containing 12 mg of scilliroside. Vomiting appeared a few minutes later and persisted for 48 hours. At the 20th hour, when he was admitted, EKG revealed a complete atrio-ventricular block which disappeared only on the 4th day. The repolarization abnormalities characteristic of digitalization persisted still further until the 12th day. PMID- 1941707 TI - Serum postdexamethasone prolactin measures in depressive patients and control subjects. AB - Recently, some researchers noted significant positive relationships between postdexamethasone serum cortisol and prolactin levels, whilst endogenous depressives exhibited a significantly lower suppression of prolactin by dexamethasone than non-endogenous patients or normal controls. To ascertain the extent of prolactin responses to dexamethasone in severely depressed patients, we measured 8 a.m. pre- and postdexamethasone prolactin levels in 104 depressed and 42 normal subjects. Serum cortisol levels were also determined in depressed patients before and after dexamethasone administration. We found a significant suppressive effect of dexamethasone on prolactin levels. There were no significant differences either in pre- or postdexamethasone prolactin, or in actual dexamethasone-induced decrements in prolactin between normal controls, melancholics, simple major or minor depressed subjects. We have not found any significant relationships between cortisol and prolactin, either under baseline or postdexamethasone conditions. PMID- 1941708 TI - Performance of two forms of a computer psychiatric screening interview: version I of the DISSI. AB - This study reports on the performance of two forms of version I of the Diagnostic Interview Schedule (DIS) computer screening interview, using the traditional interviewer-administered DIS (T-DIS) as the standard. The screening interview was either self-administered (called the S-DISSI) with the subject keying in responses, or interviewer-administered (I-DISSI), with the interviewer keying in the subject's responses. Sensitivity and specificity for both forms were ample (excluding antisocial personality), ranging from 60% to 100% for sensitivity and 54% to 95% for specificity. Concordances with the T-DIS were similar for both forms of the screening interview, ranging from .10 to .87 and compared favorably to those reported by other investigators. The I-DISSI took on average 30 min less than either the T-DIS and S-DISSI. Since the performances of both versions were equivalent, the decision to use either may be based on available resources and characteristics of the study population. PMID- 1941709 TI - Negative symptoms and reaction time in schizophrenia. AB - This study explored the association of negative symptoms and reaction time. Negative symptoms were specifically associated with reaction time slowing and variability in schizophrenics, but not in affective disorders. The finding of specificity did not extend to other measures of the deficit syndrome nor to motor performance. An abbreviated version of the negative symptom scale was especially effective in separating groups. PMID- 1941710 TI - Are secular trends in major depression an artifact of recall? AB - There is evidence that rates of major depression have increased over this century, with successive birth cohorts showing increased lifetime risks and earlier ages of onset. Two memory effects have been considered possible artifactual causes of these trends: age-related forgetting and postdating early episodes. In this study, relatives were reinterviewed six years after study entry using interviewers blind to initial reports. We examined the stability of lifetime diagnoses of MDD and ages of first onset. Older relatives were no more likely than younger ones to lose diagnoses nor to postdate their ages of first MDD onset. This is evidence that memory artifacts are not solely responsible for the observed secular trends. PMID- 1941711 TI - Evaluation of seasonality in six clinical populations and two normal populations. AB - The Seasonal Pattern Assessment Questionnaire (SPAQ) was used to evaluate retrospectively self-reported seasonal changes in mood and behavior (seasonality) of two normal and six clinical populations: patients with winter-seasonal affective disorder (SAD), summer-SAD, eating disorders, bipolar affective disorder, major depressive disorder and subsyndromal winter-SAD. The SPAQ successfully discriminated between groups expected to have high seasonality scores, such as winter-SAD, summer-SAD and subsyndromal winter-SAD, and normal controls. Bipolars and major depressives had normal seasonality scores. Patients with eating disorders had unexpectedly high scores. There was a general tendency for all groups to eat and sleep more and to gain weight in the winter. The implications of these findings are discussed. PMID- 1941712 TI - Post-traumatic stress disorder: issues of co-morbidity. AB - There is considerable controversy over whether or not post-traumatic stress disorder (PTSD) should be considered as a separate diagnostic entity. The present study utilized the Symptom Checklist-90 (SCL-90) in order to examine the degree of overlap between PTSD and the related diagnoses of anxiety, depression and obsession-compulsion in a group of Israeli Lebanon War PTSD casualties. We found that the SCL-90 was able both to identify and discriminate between the clinical groups. Multiple discriminant analysis showed that although there is overlap between PTSD and obsessive-compulsive disorder, PTSD is, in fact, discriminated from all the other patient groups. PMID- 1941713 TI - Physiology and morphology of descending neurons in pheromone-processing olfactory pathways in the male moth Manduca sexta. AB - 1. We have characterized the responses and structure of olfactory descending neurons (DNs) that reside in the protocerebrum (PC) of the brain of male sphinx moths Manduca sexta and project toward thoracic ganglia. 2. Excitatory responses of DNs to pheromone blends were of two general types: (a) brief excitation (BE) that recovered to background in less than 1 s after the stimulus, and (b) long lasting excitation (LLE) that outlasted the stimulus by greater than or equal to 1 s and, in many cases, as long as 30 s. Individual pheromone components were ineffective in eliciting LLE. 3. Some neurons showing LLE also exhibited state dependent responses to pheromonal stimuli. When such neurons were in a state of low background firing, stimulation with pheromone blend elicited LLE. When they were in a state of LLE, an identical stimulus reduced firing for 5-10 s after which firing gradually increased to the initial higher level. 4. Thirteen stained DNs were reconstructed from serial sections for detailed analysis of their morphology in the brain. DNs exhibiting LLE had neurites concentrated in the lateral accessory lobes (LALs) in the protocerebrum and adjacent neuropil. Most DNs exhibiting only BE to pheromonal stimuli and other DNs showing responses only to visual or mechanosensory stimuli did not have branches in the LALs. PMID- 1941714 TI - Spectral and temporal gating mechanisms enhance the clutter rejection in the echolocating bat, Rhinolophus rouxi. AB - Doppler shift compensation behaviour in horseshoe bats, Rhinolophus rouxi, was used to test the interference of pure tones and narrow band noise with compensation performance. The distortions in Doppler shift compensation to sinusoidally frequency shifted echoes (modulation frequency: 0.1 Hz, maximum frequency shift: 3 kHz) consisted of a reduced compensation amplitude and/or a shift of the emitted frequency to lower frequencies (Fig 2). Pure tones at frequencies between 200 and 900 Hz above the bat's resting frequency (RF) disturbed the Doppler shift compensation, with a maximum of interference between 400 and 550 Hz (Fig. 1). Minimum duration of pure tones for interference was 20 ms and durations above 40 ms were most effective (Fig. 3). Interfering pure tones arriving later than about 10 ms after the onset of the echolocation call showed markedly reduced interference (Fig. 4). Doppler shift compensation was affected by pure tones at the optimum interfering frequency with sound pressure levels down to -48 dB rel the intensity level of the emitted call (Fig. 5, 6). Narrow bandwidth noise (bandwidth from +/- 100 Hz to +/- 800 Hz) disturbed Doppler shift compensation at carrier frequencies between -250 Hz below and 800 Hz above RF with a maximum of interference between 250 and 500 Hz above resting frequency (Fig. 7). The duration and delay of the noise had similar influences on interference with Doppler shift compensation as did pure tones (Fig. 8, 9). Intensity dependence for noise interference was more variable than for pure tones (-32 dB to -45 dB rel emitted sound pressure level Fig. 10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941715 TI - The development of the Jamming Avoidance Response (JAR) in Eigenmannia: an innate behavior indeed. AB - In its Jamming Avoidance Response (JAR), the gymnotiform electric fish Eigenmannia shifts its electric organ discharge (EOD) frequency away from similar interfering frequencies. Continual behavioral measurements were carried out in 164 juvenile fish until a correct JAR emerged. Sixty-four of these fish were raised in complete isolation, the remainder in a community of their siblings. A correct JAR emerged in fish of 1.2-1.6 cm in body length, corresponding to a developmental age of 24-32 days. In 6 of 164 fish, the emergence of a correct JAR followed an interim appearance of an incorrect JAR, which involved frequency shifts in the direction opposite to those of a correct JAR. The fish raised in isolation developed the same forms of behavior and showed the same sequence in their appearance as did socially raised fish. This indicates that the JAR and its developmental schedule are innate. The appearance of an incorrect JAR suggests initial errors or incompleteness in the wiring of central nervous connections. A correct JAR ultimately emerged even if a stimulus regimen was offered that 'rewarded' frequency shifts in the direction opposite to those of a correct JAR. This indicates that the development of the JAR is immune to experimental alterations of sensory experience. PMID- 1941716 TI - Action of the octavolateralis efferent system upon the lateral line of free swimming toadfish, Opsanus tau. AB - The activation and action of the octavolateralis efferent system was studied by chronic recordings of discharge patterns from putative efferent and single primary afferent neurons in alert, free-swimming toadfish. Efferent axons isolated in the anterior lateral line nerve showed phasic discharges following touch stimuli applied to the head or trunk and demonstrated sustained discharges to visual stimuli. Resting discharge patterns of primary afferents were categorized into irregular, burster, regular, and silent classes. Afferent discharges were often modulated by low frequency (less than 1 Hz) water movement around the head generated during respiratory movements. When fish with recording electrodes implanted in the lateral line nerve were visually stimulated, modulated peak discharges and average (DC) firing rates were inhibited in irregular-type units only. Inhibition of irregular-type afferent neurons also followed visual presentation of natural prey and persisted long after prey stimuli were removed from view. The inhibitory action upon lateralis afferents when activated by biologically significant visual stimuli leads to the hypothesis that the octavolateralis efferent system functions in the peripheral processing of information carried by the lateral line in natural settings. PMID- 1941717 TI - Circadian photoreception in the retinally degenerate mouse (rd/rd). AB - We have examined the effects of light on circadian locomotor rhythms in retinally degenerate mice (C57BL/6J mice homozygous for the rd allele: rd/rd). The sensitivity of circadian photoreception in these mice was determined by varying the irradiance of a 15 min light pulse (515 nm) given at circadian time 16 and measuring the magnitude of the phase shift of the locomotor rhythm. Experiments were performed on animals 80 days of age. Despite the loss of visual photoreceptors in the rd/rd retina, animals showed circadian responses to light that were indistinguishable from mice with normal retinas (rd/+ and +/+). While no photoreceptor outersegments were identified in the retina of rd/rd animals (80 100 days of age), we did identify a small number of perikarya that were immunoreactive for cone opsins, and even fewer cells that contained rod opsin. Using HPLC, we demonstrated the presence and photoisomerization of the rhodopsin chromophore 11-cis retinaldehyde. The rd/rd retinas contained about 2% of 11-cis retinaldehyde found in +/+ retinas. We have yet to determine whether the opsin immunoreactive perikarya or some other unidentified cell type mediate circadian light detection in the rd/rd retina. PMID- 1941718 TI - Visual perception of texture in aggressive behavior of Betta splendens. AB - In order to elucidate the role of texture in fish vision, the agonistic behavior of male Siamese fighting fish (Betta splendens) was tested in a response to models composed by means of image processing techniques. Using the models with the contour shape of a side view of Betta splendens in an aggressive state, the responses were vigorous when there was a fine distribution of brightness and naturalistic color, producing textures like a scale pattern. Reactions became weaker as the brightness and color distribution reverted to more homogeneous levels and the scale pattern disappeared. When the artificial models with the circular contour shape were used, models with the scale pattern evoked more aggressive behaviors than those without it, while the existence of spherical gradation affected the behavior slightly. These results suggest that texture plays an important role in fish visual perception. PMID- 1941719 TI - Interactions between two antagonistic reflexes in the nematode Caenorhabditis elegans. AB - 1. Antagonistic reflexes that use the same final common path cannot be activated simultaneously; as a consequence one reflex often inhibits the expression of the other. Results of experiments with two antagonistic reflexes in Caenorhabditis elegans showed that the reflex inhibition in this simple animal is the same as in more complex organisms. Thus C. elegans can serve as a model system for studying the neural mechanisms underlying these behavioral patterns. 2. In adult C. elegans tail-touch normally elicits forward movement, while tap normally elicits backward movement. When tail-touch is delivered 1 s before a tap, reversals to the tap are inhibited and the magnitude of any reversal that does occur is reduced. 3. The relative magnitude of the 2 stimuli, tail-touch and tap, affects the amount of inhibition observed. 4. The effectiveness of tail-touch as an inhibitory stimulus can be varied as a result of experience. Habituating the response to tail-touch decreased the inhibition of reversal to tap following a tail-touch. 4. The tail-touch induced inhibition of reversal to tap diminishes over an interval of at least 10 s; however, following the inhibition an enhancement of responding to tap is seen. 6. Inhibition of reversal to tap is present in worms of all stages of development including newly hatched worms. PMID- 1941720 TI - Encoding repetition rate and duration in the inferior colliculus of the big brown bat, Eptesicus fuscus. AB - 1. Encoding of temporal stimulus parameters by inferior collicular (IC) neurons of Eptesicus fuscus was studied by recording their responses to a wide range of repetition rates (RRs) and durations at several stimulus intensities under free field stimulus conditions. 2. The response properties of 424 IC neurons recorded were similar to those reported in previous studies of this species. 3. IC neurons were classified as low-pass, band-pass, and high-pass according to their preference for RRs and/or durations characteristic of, respectively, search, approach, or terminal phases of echolocation. These neurons selectively process stimuli characteristic of the various phases of hunting. 4. Best RRs and best durations were not correlated with either the BFs or recording depths This suggests that each isofrequency lamina is capable of processing RRs and durations of all hunting phases. 5. Responses of one half of IC neurons studied were correlated with the stimulus duty cycle. These neurons may preferentially process terminal phase information when the bat's pulse emission duty cycle increases. 6. While the stimulus RR affected the dynamic range and overall profile of the intensity rate function, only little effect was observed with different stimulus durations. PMID- 1941721 TI - PTSD and the Vietnam veteran: the battle for treatment. AB - 1. Patients with post-traumatic stress disorder (PTSD) often encounter treatment that is complicated by professional bias, personal issues, countertransference, and pathological staff dynamics. 2. Treatment is further complicated by diagnostic confusion, the dual diagnoses of substance abuse or depression, and symptoms that mimic personality disorders or psychosis. 3. The special circumstances of the Vietnam conflict that contributed to the susceptibility and etiology of PTSD are the individual characteristics of those who served, the special nature of the war itself and the military strategies used, and the psychosocial and cultural milieu in which it occurred. PMID- 1941722 TI - You can get there from here: guide to problem definition in policy development. AB - 1. Nurses can enhance their abilities to formulate and implement health policy through the use of the assessment part of the nursing process. 2. Problem definition, the first step in policy development, includes identifying the issues, discussing and framing the issues, analyzing data and resources, and deciding on a problem definition. 3. Problem definition develops as an interaction between an instrumental, or cognitive, component and an expressive component, which represents the contextual setting of the problem. 4. Problem definitions change over a course of events. Current solutions may lead to new concerns and issues that then require new problem definitions. PMID- 1941723 TI - Ritualistic behavior: breaking the cycle. AB - 1. Recent studies reveal that OCD occurs at rates of 25 to 60 times greater than previous estimates. 2. Currently, biological theories of causation have been cited by multiple researchers. 3. Behavioral therapy and medication therapy have emerged as treatments of choice in OCD. PMID- 1941724 TI - Staying well-nourished battles AIDS. PMID- 1941725 TI - Learning opportunities through camping for mental health nursing. AB - 1. To equip nurses with the skills necessary for working with disturbed people, nurse educators need to be mindful of not watering down the essential skills necessary for nurses to deal with difficult behaviour in all branches of nursing. 2. These components of a mental health clinical experience should equip the graduate to deal with the pressures of dealing with disturbed people in any environment, as the skills learned generalize to any branch of nursing. 3. Universities can combine with traditional hospital services and community mental health services to provide services to clients with mental illness. An additional benefit is in providing students with an intensive clinical learning experience that reinforces the theory taught in the classroom. PMID- 1941726 TI - Real life learning. Alternative to clinical skills development. AB - 1. Pressure from educational institutions on clinical facilities necessitates the creation of alternative strategies that enable students to develop clinical skills outside the artificial atmosphere of a nursing laboratory or the formal clinical setting. 2. Assignments covering grief and loss experienced by the elderly; problems in performing activities of daily living experienced by the non elderly; and existential anxieties experienced by the elderly help students to realize that such problems are not confined to those residing in institutional settings. 3. Each of these assignments sensitizes students to the practical reality of a variety of theoretical frameworks, which provides students with the opportunity of applying theory to practice in a nonthreatening environment. PMID- 1941727 TI - Out of the darkness: group cognitive therapy for depressed elderly. AB - 1. Depression affects an estimated 50% of the population over age 65. With the current expansion of the elderly in this country, the problem will continue to increase. 2. Depressed individuals view situations negatively when more positive interpretations are equally valid. The thrust of cognitive therapy is to replace the faulty and negative perceptions with more valid and positive ones. 3. Cognitive therapy was found to be effective in the elderly. Residents attended sessions regularly, and the change in the depression level for group participants was highly significant statistically and clinically noticeable. PMID- 1941728 TI - Homeward bound. Broadening student experience with home visits. AB - 1. Because of patients are rapidly discharged after medication stabilization or crisis resolution, tertiary care in the home is emerging as an integral part of current psychiatric care. Students miss a valuable opportunity to participate in psychosocial rehabilitation if the clinical rotation is limited to an inpatient setting. 2. Guiding the client toward mental stabilization is the process of psychiatric care; outcomes are most apparent in the home. 3. Nursing is moving into psychiatric case management and continues to provide home care as a traditional role. Student home visits promote awareness of nursing responsibilities to families beyond the institution. PMID- 1941729 TI - A nurse's role in Operation Desert Storm. Psychosocial nursing in a war. PMID- 1941730 TI - Post-traumatic stress disorder: a role for psychopharmacology? PMID- 1941731 TI - Heading off violence with verbal de-escalation. AB - Respect for the rights and dignity of patients is the underlying principle of therapeutic communication. Its effective practice requires the nurse to identify personal issues, stressors, and one's own anxiety and effectiveness levels. It is important that the caregiver maintain self-control to help others control themselves. By constantly observing patient behavior, the nurse should be able to detect agitation and intervene in a timely fashion, avoiding physical confrontation and the physical restraints that are its usual consequence. To make this outcome possible, the nurse should learn to recognize signs of agitation and escalation; should practice presenting himself or herself as a calm, caring professional; and should maintain poise even when facing a potentially violent patient. The nurse should remain open-minded, knowing that patients frequently react to assumptions made about them, and use the information acquired to find acceptable alternatives to aggression. These alternatives should be presented to the patient, making the choices clear, yet allowing the dignity of choice. Every effort should be made to provide opportunity for patients to be in control of their own behavior. Physical confrontation should always be a last resort, and one used only when there is a clear danger of immediate physical harm to a patient or staff member. Keep in mind that the use of force is an encouragement to aggressive behavior and a hindrance to treatment. Effective use of therapeutic communication encourages patients to express their feelings and become cooperative partners in their treatment. PMID- 1941732 TI - Factors affecting limb salvage and mortality in patients undergoing femoral embolectomy. AB - The management and outcome of 131 acute femoral arterial occlusions in 126 patients over a period of 7 years is presented. The emboli were of cardiac origin in 82% of cases; 96% of the patients were treated with thromboembolectomy. The overall mortality rate was 26% with a limb salvage rate of 88% amongst the survivors. There was an increased risk of mortality in patients having both atrial fibrillation and myocardial infarction, saddle emboli and those having delayed embolectomy after 24 h. Only the latter was found to be statistically significant. One-third of the patients who died had a failed embolectomy. An early fasciotomy helped in preventing permanent neurological deficit in patients with compartment syndrome. PMID- 1941733 TI - Prostaglandins in the treatment of reflux oesophagitis: double-blind placebo controlled clinical trial. AB - The efficacy of the prostaglandin analogue, rioprostil, in the treatment of reflux oesophagitis has been assessed in a double-blind, randomized, placebo controlled trial of 25 patients with endoscopic and histological evidence of reflux oesophagitis. At the beginning and end of the study, endoscopic appearances were graded 0-4 (0 = no oesophagitis, 4 = severe oesophagitis) and the symptoms of heartburn, regurgitation, pain and dysphagia were each graded 0-3 (0 = none, 3 = severe). Fourteen patients received rioprostil, 300 micrograms twice daily, and 11 patients received identically marked placebo for a period of 12 weeks. At the end of the study there were no significant differences between the groups in mean (s.d.) endoscopic grading (rioprostil 2.4 (1.3); placebo 1.9 (0.9)) and mean (s.d.) cumulative symptom score (rioprostil 2.5 (3.1); placebo 2.6 (1.5)). Five patients in the rioprostil group reported diarrhoea. Rioprostil had no significant benefit over placebo in the treatment of reflux oesophagitis. PMID- 1941734 TI - Potential use of tumour marker CA 15-3 in the staging and prognosis of patients with breast cancer. AB - The tumour marker CA 15-3 has been assayed in 130 patients with breast cancer and correlated with stage of their disease at presentation. The median value of CA 15 3 (43 kU/l) in 26 patients with stage IV disease was significantly higher than the median for 97 patients classified as stage I or II (17 kU/l). Values were elevated in 18 of 21 (86%) patients with bone metastases at presentation. For the 41 patients with stage I or II disease presenting with levels of CA 15-3 of greater than 20 kU/l, the disease-free interval and survival were significantly less than for 56 patients presenting with levels of less than 20 kU/l. CA 15-3 provides additional information to conventional staging tests for patients presenting with breast cancer and may also have a role as a prognostic indicator. This may be particularly useful in the selection of patients for neoadjuvant therapy. PMID- 1941735 TI - Eventration of the diaphragm in children. AB - Diaphragmatic plication is a safe, well tolerated procedure for congenital diaphragmatic eventration. It is the treatment of choice in neonates with respiratory distress following phrenic nerve injury. The abdominal approach is as good as the thoracic and may be safer in cases with central eventration and when the diagnosis of congenital diaphragmatic hernia cannot be excluded with confidence. However, in phrenic nerve paralysis the thoracic approach is superior in showing the anatomical distribution of the phrenic nerve. Experience with eight paediatric patients treated for diaphragmatic eventration is reported. Five had congenital eventration of the diaphragm and three had acquired eventration. All patients except one required surgical plication of the diaphragm. Three patients developed minor postoperative complications and all patients were alive and well on follow-up. It appears that diaphragmatic plication is a safe and well tolerated procedure for symptomatic diaphragmatic eventration. PMID- 1941736 TI - Helicobacter pylori and Meckel's diverticulum. AB - Helicobacter pylori is invariably associated with peptic ulceration of the upper gastrointestinal tract. This has led to speculation about its pathogenic role in peptic ulceration. The literature and this present study show that H. pylori is not often associated with peptic ulceration in Meckel's diverticulum and hence it is unlikely that it has any significant role in peptic ulceration at this site. PMID- 1941737 TI - Intra-abdominal abscesses in children. AB - Forty-one intra-abdominal abscesses in 30 Nigerian children seen over a 2-year period at the Obafemi Awolowo University Teaching Hospital were studied prospectively to determine their location, aetiology, microbiology and clinical course. Thirty-four abscesses (83%) were intraperitoneal with the subphrenic spaces and pelvis being the commonly involved intraperitoneal sites. Six abscesses (15%) were retroperitoneal while there was only one visceral abscess (2%). Diseases of the gastrointestinal tract occurring in 20 patients (67%) were responsible for the majority of intraperitoneal abscesses, while suppurating external iliac adenitis was the major cause of retroperitoneal abscesses. There were 62 microbiological isolates, with 52% being anaerobic bacteria and 47% aerobic bacteria. A fungus, Candida, was isolated once (2%). Escherichia coli and Staphylococcus aureus were the commonest aerobic bacteria, while Bacteroides and anaerobic streptococci were the commonest anaerobes. Sixteen patients (53%) had a mixed flora of aerobic and anaerobic bacteria, while in seven patients each (23%) only aerobic or anaerobic bacteria were isolated. The mortality rate in this series was 23%. Association of an intra-abdominal abscess with remote organ failure, postoperative anastomotic leakage, non-localization of the abscess within the peritoneal cavity and gastrointestinal perforation due to typhoid enteritis was found to portend poor prognosis. PMID- 1941738 TI - Stapling techniques to facilitate resection of the head of the pancreas. AB - Thirteen patients underwent duodenocephalopancreatectomy (DCP) with the mechanical staplers to divide the pancreatic neck and to secure haemostasis of the retroportal pancreatic lamina. The stapling techniques used on the pancreas are described. In nine patients with DCP the stapled distal pancreas was anastomosed to the jejunum with Roux-en-Y drainage; one pancreatic complication and no deaths were observed. In four other patients undergoing DCP who were at high risk for severely compromised general conditions, reconstruction of the digestive tract was simplified by leaving the stapled distal pancreas definitively closed: pancreatic complications were recorded in two cases, with no deaths. Mechanical staplers considerably facilitated resection of the neck of the pancreas and of the retroportal pancreatic lamina. All 13 patients who underwent DCP with the use of stapler techniques on the pancreas, including four high-risk patients, were discharged to convalesce on an oral diet after a median postoperative hospital stay of 23 days (range 16-90 days). PMID- 1941739 TI - Carcinoma of the gallbladder: a survey of cases in Wessex 1982-1989. AB - The 95 cases of carcinoma of gallbladder diagnosed in Wessex in the period January 1982-June 1989 have been reviewed. The median age of these patients was 72 years and 75% were women. These data have been compared with those for all cholecystectomies performed in Southampton for this period. The poor prognosis of this tumour has been confirmed, with only four patients currently alive at 8, 24, 30 and 72 months after operation. Modifications to current staging systems are proposed, which may promote a more rational approach to therapy in the future. PMID- 1941740 TI - C-reactive protein in right iliac fossa pain. AB - C-reactive protein (CRP) and full blood counts were performed on 60 consecutive patients admitted with right iliac fossa pain. Of these, 31 patients had appendicitis and six had a negative appendicectomy. The CRP was raised in 29 (94%) patients with appendicitis and was not raised in five (83%) patients who underwent a negative appendicectomy. In the cases of appendicitis the CRP was significantly raised more often than the white blood cell count (WBC) (P less than 0.05, chi 2 = 3.98). In 30 (97%) patients who had appendicitis the CRP or white blood cell count was elevated. CRP is of value in indicating acute pathology and its routine performance may decrease the negative appendicectomy rate. PMID- 1941741 TI - Review of the histopathological findings in appendices removed for acute appendicitis in Nigerians. AB - The vermiform appendix is a frequent surgical specimen in most routine histopathology laboratories. This is because acute appendicitis is one of the commonest reasons for undertaking emergency laparotomy in most hospitals, even in developing countries. Three hundred and sixteen appendices removed for acute appendix in our hospital over a 10-year period were analysed, of which 37 (11.7%) were found to be normal while 221 (69.9%) showed histopathological evidence of acute inflammation. There were 25 cases of chronic appendicitis, four (1.3%) of which were granulomatous. Of these, schistosomal appendicitis was observed in three cases (0.95%) and tuberculous appendicitis was seen in one case. Of the 33 cases classified as miscellaneous, intraluminal ova of parasites with phlegmonous eosinophilic infiltration of the appendix was observed in 17 cases (5.4%) and Toxoplasma appendicitis was observed in five cases. Carcinoid tumour was diagnosed in three cases (0.95%), and in two of these the tumour had spread beyond the appendix. PMID- 1941742 TI - Endoscopic transanal resection of rectal lesions: facilitation by adaptation of Lord's dilator. AB - A wide variety of techniques are available to remove lesions within the anal canal and rectum. Endoscopic transanal resection is a well tolerated procedure which achieves good palliation. Leakage of glycine from the rectum during the procedure can be problematic. To overcome this problem a Lord's dilator has been specially adapted to enable the passage of a urological resectoscope so preventing leakage of glycine during the procedure and improving operator acceptability. This technique of transanal resection with the adapted Lord's dilator provides a cheap and effective way of treating some rectal lesions largely utilizing existing equipment. PMID- 1941743 TI - Surgical audit: variations in wound infection rates of individual surgeons. AB - A prospective survey of 1086 general surgical in-patients was carried out in West Dorset district to determine the incidence of postoperative infections for individual surgeons. A total of 79 cases were diagnosed as having become infected, resulting in an overall infection rate of 7.3%. For all cases the infection rate for individual surgeons varied from 3.9 to 14.6% (P less than 0.005; chi 2 test). For the clean operative category only, the infection rate varied from 2.9 to 20.0% (P less than 0.0005; chi 2 test). The results demonstrate the value of routine surgical audit in elaborating the variation in clinical outcomes for individual surgeons. Clinical audit can identify the need for extra supervision and training of junior staff and peer review for senior clinicians. PMID- 1941744 TI - Surgery in HIV-positive and AIDS patients: indications and outcome. AB - We have reviewed the indications for and outcome of surgery in 147 patients who were seropositive for human immunodeficiency virus (HIV), 100 of whom have developed acquired immunodeficiency syndrome (AIDS). There were 256 operations; the commonest indications were anorectal conditions (34%), central venous access (21%), lymph node and soft tissue biopsy (15%) and an important minority underwent laparotomy (4%). Complications occurred in 20% of operations and repeat procedures were required in 35 patients. Both were of equal frequency in the HIV and AIDS populations. Most operations were therefore minor, and achieved satisfactory results with an acceptable morbidity. The possibility of HIV-related infection or malignancy affected the diagnostic and therapeutic approach, particularly in those considered for anorectal surgery or laparotomy. With increasing numbers of HIV-infected patients, knowledge of the types of surgery required and the likely outcome is important to enable provision of a safe and effective surgical service. PMID- 1941745 TI - Prospective study of two management strategies for epistaxis. AB - Two different management strategies were applied prospectively and consecutively for 12 months each for epistaxes requiring hospital admission. Patients who did not respond to 48 h nasal packing were treated more successfully and more economically by submucous resection of the nasal septum than by delayed arterial ligation. PMID- 1941746 TI - Pilomatrixoma as a diagnostic problem: the Edinburgh experience. AB - The purpose of this retrospective study was to review the paediatric experience in Edinburgh of a relatively benign skin tumour. The study group consisted of children less than 13 years of age with a pathological diagnosis of pilomatrixoma over the period between January 1980 and December 1989. The results reaffirmed a female preponderance. The majority of lesions had been present for less than 1 year at the time of removal but were mainly misdiagnosed at the time of primary consultation or at removal. Although pilomatrixoma has a 'typical' appearance pathologically there are problems with preoperative diagnosis. Sites of occurrence are comparable with the dermoid type of cyst and the possibility must be considered of an embryological origin for pilomatrixoma. PMID- 1941747 TI - Preparation of skin for surgery. AB - A survey of 113 hospitals in the UK was performed to assess current practices regarding skin preparation for surgery. The findings of the survey are presented and where relevant compared with a similar survey conducted in 1983. It was found that, despite scientific evidence supporting change, traditional practices still dominate. This evidence is discussed and, based on this, some changes in practice are suggested. PMID- 1941748 TI - External fixators and their use. PMID- 1941749 TI - Risk of deep infection with intramedullary nailing following the use of external fixators. AB - A retrospective review was carried out to assess the incidence of deep infection occurring when intramedullary nailing was performed following the use of an external fixator. Three groups of patients were identified: group 1 in which the external fixator was used in initial fracture management (ten cases, nine patients), group 2 in which the external fixator was used in the management of established non-union (seven cases, seven patients), and group 3 in which the external fixator was used in limb lengthening procedures (eight cases, eight patients). All the 25 cases reviewed had clinical evidence of pin track infection before removal of the external fixator. After removal of the fixator it is our normal policy to wait for the pin sites to become dry before performing intramedullary nailing. In only one case, where there was a history of preceding recrudescent osteomyelitis, was there evidence of deep infection being reactivated following intramedullary nailing. We therefore conclude that pin track infection does not seem to be a contraindication to the subsequent use of an intramedullary nail, providing that underlying active osteomyelitis is not present. A delay of 7 to 14 days after removal of the fixator is recommended. Some problems experienced during nailing are highlighted, and solutions proposed. PMID- 1941750 TI - Management of tibial fractures with the orthofix dynamic external fixator. AB - We report our experience with the use of the Orthofix external fixator for the management of closed and open tibial fractures. One hundred fractures were treated in 96 patients between May 1985 and December 1989. There were 47 closed and 53 open fractures. Of the open fractures, 11 were grade I, 16 were grade II and 26 were grade III. Forty-five closed fractures and 49 open fractures went on to solid bony union in an average of 15.2 and 20.5 weeks, respectively. Non-union requiring operative intervention occurred in two closed and four open fractures (6%). The other main complications were pin track infection (30% of cases) and malunion which occurred in 14% of closed fractures and 32% of open fractures. We concluded that dynamic axial fixation is a useful method of treatment for open and difficult closed tibial fractures. Our experience indicates that malunion and pin track infection remain common problems and have still to be overcome. PMID- 1941751 TI - Primary hyperparathyroidism associated with carcinoid of the thymus. PMID- 1941752 TI - Spontaneous mediastinal haemorrhage. PMID- 1941753 TI - A water pump for emergency endoscopy. PMID- 1941754 TI - Amputation and cisplatin for treatment of canine osteosarcoma. AB - Seventy-one dogs with histologically confirmed appendicular osteosarcoma were evaluated. Seventeen dogs were treated with amputation and two postoperative [corrected] doses of IV cisplatin given 21 days apart (group 1). Nineteen dogs were treated with IV cisplatin 21 days before amputation, with a second dose given immediately after amputation (group 2). Thirty-five dogs were treated by amputation of the affected limb with no chemotherapy (group 3). The median disease-free interval for group 1 was 226 days, and 177 days for group 2. This was not significantly different. The median survival time was 262 days for group 1, 282 days for group 2 and 119 days for group 3. Group 1 and 2 dogs had survival times that were significantly longer than for dogs in group 3. Two IV courses of cisplatin given before or after amputation appears to improve the survival of dogs with osteosarcoma. PMID- 1941755 TI - Pharmacology of furosemide in the horse: a review. AB - Furosemide, a diuretic, is frequently administered to horses for the prophylaxis of exercise-induced pulmonary hemorrhage and the treatment of a number of clinical conditions, including acute renal failure and congestive heart failure. Furosemide increases the rate of urinary sodium, chloride, and hydrogen ion excretion. Plasma potassium concentration decreases after furosemide administration but urinary potassium excretion in horses is minimally affected. Renal blood flow increases after furosemide administration. Systemically, furosemide increases venous compliance and decreases right atrial pressure, pulmonary artery pressure, pulmonary artery wedge pressure, and pulmonary blood volume. The systemic hemodynamic effects of furosemide are only manifest in the presence of a functional kidney, but can occur in the absence of diuresis, emphasizing the importance of the renal-dependent extra-renal effects of furosemide. The renal and systemic hemodynamic effects of furosemide are modified by prior administration of nonsteroidal anti-inflammatory drugs. Furosemide administration attenuates exercise-induced increases in right atrial, aortic, and pulmonary artery pressures in ponies. Furosemide prevents exercise and allergen induced bronchoconstriction in humans and decreases total pulmonary resistance in ponies with recurrent obstructive airway disease. These pharmacologic effects are frequently used to rationalize its questionable efficacy in the prevention of exercise-induced pulmonary hemorrhage. Neither the effect of furosemide on athletic performance nor its efficacy in the prevention of exercise-induced pulmonary hemorrhage has been convincingly demonstrated. PMID- 1941756 TI - Analysis of survival in a retrospective study of 86 dogs with brain tumors. AB - A retrospective study of 86 dogs with brain tumors was undertaken. Sixty-nine dogs had histologic confirmation of tumor type, whereas the remaining 17 dogs had CT evidence of a brain tumor. All dogs had neurologic abnormalities. Seven dogs received no treatment, 38 dogs received only symptomatic treatment, and 41 dogs received some form of definitive treatment, in addition to medical management. Types of definitive treatment included surgery, cobalt-60 radiation, whole-body hyperthermia, 125I implants, and chemotherapy, alone or in combination. The factor that was most associated with survival duration was mode of therapy. Those dogs who were treated with cobalt-60 radiation, with or without other combinations of therapy, lived significantly longer than dogs who received surgery (+/- 125I implants), or dogs who received symptomatic treatment (P = 0.01 and P less than 0.001, respectively). After statistic adjustment for treatment, multiplicity of brain involvement (solitary vs. multiple) provided prognostic information with respect to survival (P = 0.001), with dogs who had a solitary site of involvement having a better prognosis. After further adjustment, initial neurologic dysfunction (mild/moderate vs. severe) showed significance as prognostic variable (P = 0.005). Both the mild and moderate groups had a more favorable prognosis compared with dogs who had severe initial neurologic impairment. The median survival time for the 86 dogs was 1.0 month (range: 1 day 42.4 mo). Median survival times of dogs receiving: 1) no therapy or only symptomatic therapy, 2) surgery (+/- 125I), or 3) cobalt-60 radiation (+/- hyperthermia, +/- surgery) were 0.2, 0.9, and 4.9 months, respectively. PMID- 1941757 TI - Plasma taurine concentrations and M-mode echocardiographic measures in healthy cats and in cats with dilated cardiomyopathy. AB - M-mode echocardiography was completed and plasma taurine concentrations were determined in 79 healthy cats and 77 cats with dilated cardiomyopathy (DCM). In healthy cats, a relationship was not observed between plasma taurine concentrations and any M-mode echocardiographic measurement. End-systolic and end diastolic cardiac chamber dimensions were larger; wall thickness measures were smaller; and calculations of fractional shortening were less in cats with DCM than in healthy cats. Plasma taurine concentrations less than 30 nmol/mL were detected in 7/79 healthy cats and in 52/77 cats with DCM. Of the 52 cats with DCM and an initial plasma taurine concentration less than 30 nmol/mL, 23 died or were euthanized during the first post-treatment week, 7 were lost to further study, and 22 improved after taurine supplementation. Of the 25 cats with DCM and an initial plasma taurine concentration greater than or equal to 30 nmol/mL, 9 died or were euthanatized during the first post-treatment week, and 9 were lost to further study. Two cats did not improve, of which one died and one was euthanatized 4 to 8 weeks after initiation of taurine supplementation. Five cats with a plasma taurine concentration greater than or equal to 30 nmol/mL improved after taurine supplementation. Myocardial function subsequently deteriorated in three of these cats. Two of the three cats had signs of congestive heart failure redevelop. PMID- 1941758 TI - Thoracic radiographic features of silicosis in 19 horses. AB - Clinical records and thoracic radiographs of 19 horses with a confirmed pathologic diagnosis of silicosis were reviewed. These horses had histories of varying degrees of chronic weight loss, exercise intolerance, and respiratory distress. At the time of presentation, two horses were asymptomatic. Ten horses were geldings and nine were female. The mean age of the 19 horses was 10.7 +/- 5.5 years. Fourteen horses were identified as being from the Monterey-Carmel Peninsula of midcoastal California. An abnormal, structured interstitial pulmonary pattern was identified on thoracic radiographs in each horse. The interstitial pulmonary changes were classified as miliary (13 horses), reticulonodular (4), or linear interstitial (2), and were best visualized dorsally and caudodorsally. In addition to the abnormal interstitial pulmonary pattern, areas of pulmonary consolidation were evident caudodorsally in seven horses. Other thoracic radiographic features included: hilar lymphadenopathy (4 horses), pleural effusion/thickening (4), cranial mediastinal lymphadenopathy (2), hyperinflation (1), and a discrete pulmonary mass (1). Necropsy findings in eight horses and results of lung biopsies in an additional five horses showed a diffuse, multifocal, granulomatous pneumonia with areas of pulmonary fibrosis. Cellular infiltrates included predominantly macrophages with intracellular and/or extracellular crystalline material, occasional lymphocytes, and giant cells. Similar cellular changes were also identified, during necropsy, in the hilar and tracheobronchial lymph nodes in each of the eight horses, although gross enlargement of the lymph nodes was present in only six horses. The radiographic and pathologic findings of these 19 horses are consistent with chronic or the accelerated forms of silicosis that are recognized in humans. PMID- 1941759 TI - Haematological and biochemical screening of potential Royal Naval aircrew. AB - The objective of this study was to determine which, if any, of a small range of haematological and biological tests would be of value in detecting disease risk factors as an addition to the Initial Flying Medical when screening potential Royal Naval aircrew. A retrospective review of results of haematological and biochemical profiles of 200 candidates screened at the Central Air Medical Board was used. Ninety nine candidates (49.5%) were found to have profiles outside the normal range on initial testing. Many of these were found to be normal on repeat testing or further investigation. One candidate was made permanently unfit to fly and three others had certain conditions put on their training or careers. It is concluded that most of the screening carried out serves only a limited function. It is recommended that screening should be stopped; however, should screening still be considered necessary only four tests are required, ie, fasting blood glucose, fasting total cholesterol and triglycerides, liver function test and full blood count. PMID- 1941760 TI - An orthoptist's view of St John Ophthalmic Hospital, Jerusalem before and during the Intifada. PMID- 1941761 TI - Medical Support Assistants: early experience in training. AB - This paper provides a background to the formation of the Medical Support Assistant branch of the Royal Naval Reserve. The objectives of training and the war role are stated. Detailed particulars of each year of training, together with personal experience are given. Comments about the future status of the branch and exercising are made. PMID- 1941762 TI - The effect of hand immersion on body temperature when wearing impermeable clothing. AB - The effects of hand immersion on body temperature have been investigated in men wearing impermeable NBC clothing. Six men worked continuously at a rate of approximately 490 J. sec-1 in an environmental temperature of 30 degrees C. Each subject was permitted to rest for a period of 20 minutes when their aural temperature reached 37.5 degrees C, and again on reaching 38 degrees C, and for a third time on reaching 38.5 degrees C (three rest periods in total). Each subject completed three experimental conditions whereby, during the rest periods they either: a. Did not immerse their hands (control). b. Immersed both hands in a water bath set at 25 degrees C. c. Immersed both hands in water at 10 degrees C. Physiological measures of core temperature, skin temperature and heart rate were recorded at intervals throughout the experiment. Measures of mean aural temperature and mean skin temperature were significantly (P less than 0.05) reduced if hands were immersed during these rest periods, compared to non immersion. As a result, the total work time of subjects was extended when in the immersed conditions by some 10-20 minutes within the confines of the protocol. It is concluded that this technique of simple hand immersion may be effective in reducing heat stress where normal routes to heat loss are compromised. PMID- 1941763 TI - Medical audit: a Well Woman Clinic in the Royal Naval training practice, Gibraltar. AB - In order to assess the effectiveness of patient self-selection, and the value of dedicating surgery time to a specific clinic, attendances at a Well Woman Clinic were compared with attendances for the same reasons at other times. During the nine month audit period the opportunity was also taken to overhaul the Age/Sex Register, and assess the uptake of Cervical Screening at the Garrison Medical Centre. This unit is part of the Royal Naval Training Practice in Gibraltar. PMID- 1941764 TI - Malignant ameloblastoma? A case report and review of literature outlining problems in diagnosis and treatment. AB - This paper reviews the literature on the clinical and histological diagnosis of both malignant ameloblastoma and ameloblastic carcinoma. The problems of existing classifications are emphasised and guidelines as to clearer, simpler classification are suggested. The case history emphasises the need for a clear classification between malignant ameloblastoma and ameloblastic carcinoma. PMID- 1941765 TI - Some recent Naval engagements. AB - The request for assistance from the Command, on the advice of the medical staff, reflected earlier education of such personnel. The ability to respond within an hour of being requested to do so was the result of constant paper exercises and the prior establishment of principles agreed by Command/Management. The importance of working to agreed standard operating procedures, and to be seen to be doing so, cannot be over-emphasised. What those struggling to cope with the aftermath of disaster need, is support. Such support is most likely to result from Teams operating within clear guidelines and simple principles. Where possible, the Team should contain members known to key individuals in the community being served. All these factors applied in the SPRINT response at Deal. PMID- 1941766 TI - The carcinogenic risks of low-LET and high-LET ionizing radiations. PMID- 1941767 TI - Natural radiation background in metropolitan Taipei. AB - A high-pressure ionization chamber was used to measure the natural background radiation in metropolitan Taipei, Taiwan, R.O.C. during a period in 1987-1988. The average exposure rate was 27.55 x 10(-10) C kg-1 h-1 including cosmic radiation, but the radon contribution was excluded. Scintillation survey meter, gamma-ray spectroscopy for soil samples, in-situ measurement with a NaI(Tl) detector coupled to a portable multichannel analyzer, instrumental neutron activation analysis of rock samples, and even thermoluminescent dosimeters were used as complementary measuring devices. Areas of higher radiation background were detected. They are the radium-bearing Peitou stones, an unusual occurrence of uraniferous zone at Sanhsia, and uranium precipitation in the glassy olivine basalt in a tea field at Tachi. All these areas are located in suburban sites of Taipei. Three types of building in Taipei City were selected for radon detection. No significantly elevated level of radon was detected, since Taipei is located in a semitropical area where ventilation of buildings is not a problem. PMID- 1941768 TI - Assignment of a Chinese xeroderma pigmentosum patient from Taiwan to complementation group C. AB - A 2 years and 7 months-old Chinese boy with severe skin symptoms was diagnosed as xeroderma pigmentosum (XP) at Chang Gung Memorial Hospital in Taipei, Taiwan. Skin fibroblasts derived from the patient (patient identification number, XP1CTA) were used for genetic complementation analysis by the conventional cell-fusion technique followed by measurement of ultraviolet light (UV)-induced unscheduled DNA synthesis (UDS). The level of UDS in XP1CTA cells measured by autoradiography was about 20% of that in normal cells. When XP1CTA cells were fused with cells of a representative strain from each of the complementation groups A, D, E, F, G, and H, binuclear cells showed UDS levels in the range of normal cells, demonstrating a clear complementation between XP1CTA strain and either one of these strains. XP1CTA cells failed to complement with all the five reference strains belonging to group C. From these results, the XP1CTA was unambiguously assigned to complementation group C. Sensitivity of XP1CTA cells to UV, as measured by colony-forming ability, also fell within a range of variation in UV sensitivities of these group C XP cell strains. PMID- 1941769 TI - Radiolytic degradation of cystathionine irradiated with monochromatic soft X-rays at the K-shell resonance absorption of sulfur. AB - The degradation of cystathionine was investigated using irradiation with monochromatized synchrotron X-rays at 2472 eV and 2466 eV. 2472 eV corresponds to the energy of the K-shell resonance absorption peak of the sulfur atom. The energy at 2466 eV was adopted as a reference. Cystathionine has a sulfur atom which joins two amino acid residues. This form is useful for analyzing the effect of degradation that originates from photoexcitation in the sulfur atom. The degradation products of cystathionine were detected by high performance liquid chromatography (HPLC). Of the products present, alpha-aminobutyric acid was produced threefold on irradiation with 2472 eV X-rays, as compared with the value for irradiation at 2466 eV and the same exposure. Almost the same amount of glycine was produced at the two irradiation energies. The yields of these two products were analyzed on the basis of the amount of cystathionine degraded and the number of photons absorbed by sulfur and the other elements in cystathionine. Cleavage of a bond was shown to depend on whether the bond includes an atom that absorbs the X-ray photon. PMID- 1941770 TI - The estimated cost of treating unmet dental restorative needs of Mexican-American children from Southwestern US HHANES, 1982-83. AB - The dental restorative treatment needs of Mexican-American children, aged 1-17 years, were assessed from the 1982-83 Southwestern US Hispanic Health and Nutrition Examination Survey (HHANES). This report analyzed those needs and applied a dollar cost to them, using 1982 median fees of US general practitioners. The total estimated cost required to meet those needs for the population estimate of 3,396,770 children was $236,856,772 (95% CI: $198,575,174 to $275,138,370). The mean cost per child was $69.73 (SE: 5.75). Although a majority of the children had no unmet need, 15-, 16-, and 17-year-olds had extensive needs for crowns, endodontics, and prosthetic replacement of teeth, with accompanying high costs: mean total cost per examinee was $177 (SE: 28.97), $161 (SE: 32.20), and $237 (SE: 33.26), respectively. The treatment needs were compared with the previously published regional data from the 1979-80 NIDR survey, which used the same dental restorative treatment needs (DRTN) index. The findings indicated a great need for dental treatment among Mexican-American children that appeared to exceed that of the general school-aged population. Our analysis, in providing estimates of the cost of needed treatment, might be useful in planning dental treatment programs and in comparing surveys. PMID- 1941771 TI - Dental treatment needs in an elderly population. AB - A random sample of 1,019 adults 65 years of age and older, living in their own homes, consented to a clinical dental examination and an interview. Eight hundred nine subjects were dentate and 210 were edentulous. Each dentate person was examined for caries and periodontal conditions, as well as a separate determination of restorative and extraction treatment needs. Most people in this study lacked restorative treatment needs of any kind. Blacks required restorative treatment and extractions more often than whites. Carious coronal and root surfaces, pocket depths, number of teeth, as well as educational level and time since last visit to the dentist were related to treatment needs. While clinical findings were related to treatment needs, precise determinations of treatment needs of this elderly population generally could not be based solely on clinical findings. Additional behavioral, social, and health factors appear to play a role in dentists' decisions when determining treatment needs of older persons. PMID- 1941772 TI - Oral health knowledge and habits of senior elementary school students. AB - Despite improvements in children's dental health, and significant resource allocation to health education programs, few recent studies have investigated the associations of oral health knowledge, behaviors, and status. This study of 11 year-old children (N = 6,329) in northeastern Ontario used a supervised self complete questionnaire and a clinical examination to gather baseline data on, and test associations of, caries and periodontal knowledge, self-reported oral health behaviors and source of knowledge, and oral health status. Results show the children had poor knowledge of caries preventive measures such as water fluoridation, dental sealants, and choice of snack foods. Periodontal knowledge was better, but children confused plaque and calculus. Respondents claimed good oral health habits, with 73 percent claiming to brush at least twice daily, 88 percent claiming to use toothpaste, 42 percent claim to floss at least twice weekly, and 84 percent claiming an annual dental visit. Children with the best knowledge claimed dentist and school as the sources. High knowledge was associated with good oral health habits (P less than .001) and low DMFT score (P less than .001). Good habits were not related to DMFT score (P = .1095). Logistic regression showed high knowledge was associated with English cultural status, urban school area, good habits, having a dental sealant, and attending a fluoride rinse school (P less than .05). Findings suggest a need to reinforce caries preventive teaching, to investigate the effect of cultural status, dental experience, and residence status on oral health knowledge, and to further test the efficacy of different oral health education programs delivered by different sources. PMID- 1941773 TI - The validity of self-reported oral health status in the elderly. AB - The validity of self-reported number of teeth was assessed in a random sample of 50 individuals aged 70+ by comparing self-reports in a telephone interview with results of a subsequent in-home examination by a dentist. There were no significant differences between self-report and examination data, nor was there any systematic under- or over-counting of teeth as the actual number of teeth increased. These data support the validity of self-reported dentition. PMID- 1941774 TI - Health through oral health; guidelines for planning and monitoring for oral health care: a critical comment on the WHO model. AB - Recently a joint working group of WHO/FDI published guidelines for planning and monitoring oral health care. In the report a model for calculations of future need for dental manpower was introduced as an effective planning tool. An analysis of whether the WHO model is appropriate to calculate the future need for manpower planning was carried out. It appears that the model has serious methodological shortcomings. The model expects the user to know the future oral care needs concerning preventive, special group, surgical, orthodontic, and periodontal care. In calculating future needs for restorative and prosthetic care, the model restricts itself to looking back in time and roughly calculating what has happened in the past, assuming this will happen again. PMID- 1941775 TI - The oral health status, treatment needs, and dental utilization patterns of Native American elders. AB - The purpose of this study was to evaluate the oral health status, treatment needs, and dental care utilization patterns of a Native American population aged 65-74 years. A random sample of 688 individuals was chosen and approached regarding participation in the study. Data were gathered through an interviewer administered questionnaire and an oral examination. A total of 204 individuals completed all aspects of the study. Only one participant had all 28 natural teeth, while 58.3 percent were totally endentulous. Of the 85 dentate participants, almost 53 percent required at least one extraction. The average number of required extractions in the dentate subjects was three. Although 94 percent of the sample stated they had a usual source of dental care, 40.7 percent had not visited a dentist within the last five years. Multiple regression analyses were used to determine the factors associated with total number of teeth present among the dentate participants. Years of education and time since last dental visit were the two significant predictors (P less than .05) of number of teeth present. The higher the level of education, the greater the number of teeth in later life. The number of teeth present was inversely related to years since dental treatment. Compared to the results of the National Survey of Oral Health in US Employed Adults and Seniors, this Native American sample had a higher prevalence of endentulism and utilized dental services less often than a comparable age group in the US population as a whole. PMID- 1941776 TI - Differences in need for orthodontic treatment between Native Americans and the general population based on DAI scores. AB - Clinical impressions by Indian Health Service (IHS) dentists of a greater frequency of severe dental malrelations among Native Americans than in the general US population have never been objectively confirmed. This study uses the DAI as the standard to determine whether there is a greater prevalence of severe malocclusions among Native Americans. Four hundred eighty-five Native American students in grades 7-12 from two remote sites--Pine Ridge, SD, and Many Farms, AZ -and one nonremote site--Lapwai, ID--were scored for the DAI. The mean scores from each reservation, as well as the mean score from the three reservations combined, were significantly higher, indicating poorer aesthetics, than the mean DAI score from a large sample of the general US population. These data confirm the clinical impressions of IHS dentists that Native Americans residing on reservations have significantly poorer dental aesthetics than the aesthetics found in the general US population; therefore, Native Americans have greater needs for orthodontic treatment. PMID- 1941777 TI - Ultraconservative sealed restorations: three-year results. AB - The overall objective of this clinical study was to determine the feasibility of using a sealed composite restoration to arrest caries without the removal of the carious lesion and without the traditional cavity preparation. The minimal tooth preparation (a bevel in enamel) usually did not require any anesthetic injection and conserved tooth structure. These ultraconservative sealed composite restorations placed over caries (CompS/C) have been compared with ultraconservative sealed amalgam restorations (AGS) and with the traditional outline form (unsealed) amalgam restorations (AGU). This clinical study has shown that: (1) caries can be arrested by the CompS/C restoration for a period of three years; (2) the marginal integrity of the AGS restorations showed a definite trend toward improvement as compared to the AGU restorations; and (3) complete sealant retention over posterior restorations was similar in both the CompS/C and the AGS groups during the first two years; however, at Year 3 complete sealant retention was 16 percent higher in the CompS/C than in the AGS group. PMID- 1941778 TI - An epidemiologic estimate of the critical period during which human maxillary central incisors are most susceptible to fluorosis. AB - The temporal relation between a declining fluorosis gradient and an abrupt downward shift in community drinking water fluoride concentration was evaluated through multiple correlation analysis to determine the critical time frame during which developing maxillary central incisors are most susceptible to fluoride challenge. Fluorosis data were scrutinized through a time-related series of epidemiologic "windows" or time frames of varying lengths. The placement of these time frames was in turn related to the presumed start of enamel mineralization (at birth), and ranged from zero to 60 months later. In this way, the susceptibility of developing enamel to changes in water fluoride concentration was localized. The greatest risk was associated with a four-month critical period commencing at 22 months following birth. The risk of fluorosis from exposures to a fluoride challenge acting during shorter periods was better localized than risk associated with longer exposures. We concluded (1) that human maxillary central incisors are most susceptible to fluorosis during a critical period of as little as four months' duration, commencing at 22 months of age; and (2) that for these incisors, fluoride exposure during the months prior to this period carries less risk than continued exposure for up to 36 months beyond this critical time. PMID- 1941779 TI - Oral health status, manpower, and delivery systems in a developed country--Japan. PMID- 1941780 TI - National health care: whither goeth dentistry? AB - National health insurance is reemerging as an important issue on the national health policy scene. The continuing escalation of health care costs in the US and increasing numbers of individuals without access to health services are stimulating a variety of proposals to redesign the structure and financing of the American health care system. Some change in the current system toward a more national approach to health care is inevitable in the years ahead. While dental care is subject to pressures similar to other health care services, little attention is being accorded dental services in the various national health care proposals that are being advanced. This may be due largely to organized dentistry's reluctance to define a role for itself. If dentistry is to be included in such a plan, it is essential that concerted efforts start soon and that the various public and private sectors of dentistry work collaboratively to develop the dental component to such a plan. The future oral health of the public and the future health of dentistry as a profession depend on it. PMID- 1941781 TI - National health care and the public's oral health. AB - This article presents an outline of a proposal for a national health program, together with a discussion of the necessity of inclusion of dentistry for optimum benefit to the public. A thorough restructuring of current principles of coverage, benefits, methods of payment, administration, and methods of protection of the public is proposed. Disease prevention and the role and responsibility of public health dentistry would be enhanced in such a scheme. Current total dental care expenditures should be sufficient to cover most of the costs. It is the author's belief that further tinkering with the existing health care system and the application of more bandaids can only exacerbate existing problems. PMID- 1941782 TI - Patient with a pelvic ganglioneuroma during pregnancy. PMID- 1941783 TI - Focal pelvic tenderness, pelvic pain and dysmenorrhea in endometriosis. AB - A study was conducted to determine if the increased recognition of various forms of endometriosis might have increased the ability to correlate focal tenderness with lesions. The prospective study of 82 patients revealed a strong correlation between focal tenderness on examination with the presence of deep fibrotic endometriosis and other fibrotic pathology. The data suggested that focal tenderness and depth of infiltration may direct further study in women with endometriosis. PMID- 1941784 TI - Preparation of the endometrium for ablation with a single dose of leuprolide acetate depot. AB - Several reports describe enhancing the efficacy of laser or resectoscopic endometrial ablation procedures by preparing the endometrium with danazol or progestin therapy. Because gonadotropin releasing hormone agonists have been found to inhibit the thickness and development of the endometrial lining, preparation of the endometrium for resectoscopic ablation was attempted on eight women using a single injection of 7.5 mg of leuprolide acetate depot. When the ablation was performed, one month after the injection of the medication, which had occurred on day 20-24 of the prior menstrual cycle, the endometrium was thinned in all the patients, with inactive glands, reduced vascularity and atrophic stroma. PMID- 1941785 TI - Early detection of ectopic pregnancy. Use of a sensitive urine pregnancy test and transvaginal ultrasonography. AB - We performed a prospective study to evaluate the reliability of a rapid monoclonal antibody urine pregnancy test with a sensitivity limit of 20 mIU/mL combined with transvaginal ultrasonography in the early diagnosis of ectopic pregnancy in 116 women with subacute pelvic pain and a stable general condition. The diagnosis of tubal pregnancy was confirmed with laparoscopy in 100 of the 103 women with positive sensitive urine pregnancy tests and no intrauterine gestational sac at transvaginal ultrasonography. Laparoscopy revealed a hemorrhagic corpus luteum in four of the eight subjects with negative monoclonal antibody pregnancy tests and no intrauterine gestational sac, an ovarian cyst in three and a normal pelvis in one. Of the five women with a positive pregnancy test and an intrauterine gestational sac, two had a hemorrhagic corpus luteum, two a normal pelvis and one a tubal pregnancy at laparoscopy. The sensitivity of a monoclonal antibody urine pregnancy test and transvaginal ultrasonography combined for the diagnosis of ectopic pregnancy was 99%, and the specificity was 80%, with positive and negative predictive values of 97% and 92%, respectively. PMID- 1941786 TI - High-power Nd:YAG laser ablation of the endometrium. AB - Nd:YAG laser ablation of the endometrium has become an established procedure for the treatment of menorrhagia. Early studies utilized only half the 100-120 W available from commercially produced lasers. A preliminary in vitro study was done to measure the depth of coagulation caused by the Nd:YAG laser. Fifty watts applied with the contact or noncontact technique reached a depth of 3-4 mm, while 4-5 mm was reached using 100-120 W in the noncontact mode. Thirteen patients underwent endometrial ablation using the Nd:YAG laser at 100-120 W. The mean operating time was 31 minutes. All the patients were available for follow-up, and all had excellent results. PMID- 1941787 TI - Uterine surface temperature changes caused by endometrial treatment with the Nd:YAG laser. AB - The report of a bowel injury's occurring during Nd:YAG laser ablation of the endometrium without associated uterine perforation has raised the question of the safety of the procedure. The fibers used during the initial study on temperatures caused by Nd:YAG laser treatment of uterine tissue were placed directly in contact with the tissue. The results may not be applicable to a noncontact technique. Three patients underwent measurement of surface temperature of the uterus during ablation with the Nd:YAG laser using a noncontact technique. The temperatures were within acceptable ranges in two of the patients but reached potentially dangerous levels in the third. In vitro measurements of temperatures in uterine tissue obtained from fresh hysterectomy specimens were made using fine thermocouples. The temperature rise at 10 mm was greater per joule of delivered energy at 55 W than at 95. The temperature rise varied inversely with the tissue depth when the laser was applied in a continuous fashion with a noncontact technique. When the laser was applied continuously, the temperature rise at a depth of 8 mm was significantly greater than at 10 mm. Precise knowledge of the thickness of the uterine wall may be the limiting factor in determining the safety of the procedure. PMID- 1941788 TI - Direct intrafollicular insemination. A case report. AB - This is the first case report of a documented pregnancy initiated with a new assisted reproductive technique based on direct insemination of a preovulatory follicle with ultrasonographic guidance using a transvaginal probe in women with at least one patent fallopian tube and controlled ovarian stimulation. PMID- 1941789 TI - Microsurgery and in vitro fertilization/embryo transfer for infertility resulting from distal tubal lesions. AB - The live birth rates were analyzed after 688 microsurgical operations for infertility resulting from distal tubal lesions and after 885 in vitro fertilization cycles for tubal factor infertility at the Ljubljana University Department of Obstetrics and Gynecology. The cumulative live birth rate five years after surgery was 31% (17% cases lost to follow-up). The cumulative live birth rate after four in vitro fertilization cycles for tubal infertility was 40% (8% per treated cycle). With two options for treatment, operable cases had a better prognosis than did the inoperable ones. If pregnancy did not occur two to three years after surgery, the patients underwent in vitro fertilization. The complementary use of microsurgery and in vitro fertilization has substantially improved the prognosis for infertility resulting from distal tubal lesions. PMID- 1941790 TI - Suction curettage with a tissue trap compared with sharp curettage for tissue sampling. AB - Recent reports have shown that various endometrial sampling techniques are comparable to each other. This study showed that suction curettage utilizing tissue traps is superior to sharp curettage in terms of adequacy of sampling. The results show that adequate tissue was obtained in all 114 cases, regardless of which type of curettage was utilized first. However, when sharp curettage was the second procedure, only 43 of 57 procedures yielded adequate tissue, whereas when suction curettage was the second procedure, 56 of 57 procedures yielded adequate tissue. Suction curettage utilizing tissue traps was more thorough than sharp curettage. PMID- 1941791 TI - Hyperprolactinemia and galactorrhea associated with mammary prostheses and unresponsive to bromocriptine. A case report. AB - A woman with mammary prostheses developed hyperprolactinemia and galactorrhea. The condition was unresponsive to treatment with bromocriptine and abated only with removal of the prostheses. PMID- 1941792 TI - Advanced actinomycotic pelvic inflammatory disease simulating gynecologic malignancy. A report of two cases. AB - Two women had large, solid, fixed pelvic masses simulating advanced ovarian cancer in one case and advanced cervical cancer in the other. Both patients had had plastic intrauterine contraceptive devices in situ for 7 and 17 years, respectively. Both patients required laparotomy to make the diagnosis. In both the surgery was markedly difficult because of the total absence of tissue planes. Both had obvious actinomycotic disease on routine histologic examination of the ovary and were treated with prolonged penicillin, with some, but not total, resolution of the pelvic fibrosis. The diagnosis of advanced actinomycotic pelvic inflammatory disease should be entertained in patients with a large, solid pelvic mass and an intrauterine device in situ or a recent history of intrauterine device use. PMID- 1941793 TI - Ovarian vein sampling in rapidly progressing virilization. A case report. AB - A woman presented with progressive hirsutism, deepening of the voice, clitoromegaly and increased libido. The preoperative serum testosterone level was 2,042 ng/dL. The intraoperative ovarian venous blood testosterone levels were 56,327 ng/dL on the left and 1,417 on the right. After a bilateral salpingo oophorectomy, the serum testosterone level was 20.7 ng/dL. Initial pathologic examination of the ovaries revealed no potential source of testosterone, but reexamination revealed a pure lipoid cell tumor. Intraoperative ovarian vein androgen measurements can be helpful in establishing a histopathologic diagnosis in cases of microscopic virilizing ovarian neoplasms. Ovarian vein sampling for androgen was essential in locating this patient's microscopic tumor. PMID- 1941794 TI - Testicular regression syndrome. A case report. AB - Testicular regression syndrome occurred in a 20-year-old, white, phenotypic female with a 46,XY karyotype. The basal levels of serum gonadotropins were elevated, while the testosterone was in the normal range. Estrogens were undetectable. At laparotomy no gonadal rudiments or mullerian or wolffian derivatives were found. The logical diagnosis was late embryonic testicular regression with a specific testicular insult 62-63 days after fertilization. PMID- 1941795 TI - Prevalence and severity of premenstrual changes after tubal sterilization. AB - Many women report an association between tubal sterilization and the premenstrual syndrome. While early reports suggested such a linkage, more recent studies failed to confirm this association. In an attempt to elucidate the alleged association of tubal sterilization with premenstrual changes, we compared the severity of symptoms and their possible correlates with hormonal levels in 78 sterilized and nonsterilized women with prospectively confirmed premenstrual syndrome. No significant difference could be demonstrated between the groups in both the retrospective and prospective evaluation of the severity of premenstrual syndrome symptoms as well as in luteal hormonal levels. Our data confirm that premenstrual symptoms probably are not associated with tubal sterilization. PMID- 1941796 TI - Terconazole and miconazole cream for treating vulvovaginal candidiasis. A comparison. AB - In a double-blind, randomized, multicenter study, 900 patients diagnosed with vulvovaginal candidiasis received either 0.4% (307 patients) or 0.8% (299 patients) terconazole cream or 2.0% miconazole nitrate cream (294 patients). After seven days of treatment the combined microbiologic and clinical cure rates were 87.9% for the 0.4% terconazole group, 83.8% for patients treated with 0.8% terconazole and 81.3% for the 2.0% miconazole nitrate group. The microbiologic and clinical cure rates were similarly high. The 0.4% terconazole formulation consistently provided a greater degree of symptom relief and significantly fewer adverse genital-reproductive reactions as compared with 2.0% miconazole nitrate. All three preparations were well tolerated, with only minor adverse reactions; all three seem to be useful for the treatment of vulvovaginal candidiasis. PMID- 1941797 TI - The postmenopausal palpable ovary syndrome. A retrospective review with histopathologic correlates. AB - Since its introduction in 1971 and based on experience with three patients, the postmenopausal palpable ovary (PMPO) syndrome has been widely accepted as appropriate justification for exploratory celiotomy to rule out ovarian malignancy. However, reports on only two small series have been published that address the incidence of malignancy in these patients. From March 1982 to June 1986, 20 patients underwent surgical exploration at the Naval Hospital, Bethesda, to evaluate an asymptomatic PMPO. Thirteen patients (60%) were found to have an ovarian neoplastic process. Three of the neoplasms were malignant or of borderline malignant potential, resulting in an overall malignancy rate of 15% for the PMPO syndrome. In comparing the PMPO groups, patients in the malignancy group had a statistically significant lower mean parity and greater mean number of postmenopausal years (P = .02 and .03, respectively). When the PMPO group was compared to patients with adnexal masses larger than 5 cm, there were no significant differences in the malignancy rates (15% versus 25%, P = .26), but the power was low. The data suggest that the PMPO syndrome may be clinically important. Additional studies to compare ultrasound, CA-125 and pelvic examination are indicated. PMID- 1941798 TI - Recurrent vulvovaginitis resulting from Candida species was the heavy dietary use of "artificial sweeteners". PMID- 1941799 TI - Third-trimester prediction of small-for-gestational-age infants in pregnant women with sickle cell disease. Development of the ultradop index. AB - Twenty-seven women with homozygous sickle cell disease were followed from the third trimester until delivery. All the subjects underwent both Doppler and sonographic assessment at two points in pregnancy, periods I (28-30 weeks) and II (34-36 weeks). Estimated fetal weight (EFW) was calculated. Using a continuous wave Doppler instrument, mean systolic:end diastolic (S:D) ratios were calculated to characterize the umbilical waveforms. S:D ratios greater than or equal to 3 were designated abnormal. An index, the ultra-dop, was developed that combined ultrasound EFW less than or equal to 25th percentile and S:D greater than or equal to 3. Nine of 27 infants (33%) were small for their gestational age, with a mean gestational age of 38 +/- 2 weeks. The sensitivity, specificity and predictive values were calculated for smallness for gestational age utilizing ultrasound, Doppler velocimetry and the ultradop index for periods I and II. For period I, the highest sensitivity was obtained with the ultradop index--88.9% as compared to 77.8% with Doppler scanning and 11.1% with ultrasound. The ultradop also provided the highest positive predictive value, 88.9%; it was followed by Doppler at 77.8% and ultrasound at 50.0%. In period II the ultradop index and Doppler had the same sensitivity, 88.9%, which was much higher than for ultrasound (55.6%). As for period I, the ultradop had the highest positive predictive value, 88.9%. Our data suggest that the ultradop index provides a key assessment of women with sickle cell disease at 28-30 weeks' gestation with reference to the likelihood of their giving birth to small-for-gestational-age infants. PMID- 1941800 TI - Cervex-Brush and Cytobrush. Comparison of their ability to sample abnormal cells for cervical smears. AB - A study was designed to test specimen adequacy and the detection of disease using two new cervical cytologic sampling devices, the Cervex-Brush and Cytobrush plus a modified Ayre spatula. Two clinicians used each device at random. The laboratory was blind to the sampling method, and the results were compared with those from control samples (Ayre spatula with cotton swab or alone). The 567 test samples were compared with 569 age-matched control samples. The Cervex-Brush and Cytobrush plus spatula were comparable in detecting disease, and both were improvements over the control method. Both the Cervex-Brush and Cytobrush plus spatula produced more consistent good smear quality across the age range studied than did the control method, which resulted in a lower percentage of good-quality smears in older women. Use of the Cytobrush plus spatula and the control method produced smear results the quality of which varied considerably with each clinician. PMID- 1941801 TI - Antifungal agents vs. boric acid for treating chronic mycotic vulvovaginitis. AB - Ninety-two women with chronic mycotic vaginal infections were followed with microscopic examination of the vaginal discharge during prolonged therapy with antifungal agents and boric acid. A microscopic picture unique to chronic mycotic vaginitis was observed, representing the cytologic reaction of the mucous membrane to chronic yeast infection. This diagnostic tool proved extremely effective in detecting both symptomatic and residual, subclinical mycotic infection and provided a highly predictive measure of the probability of relapse. The ineffectiveness of conventional antifungal agents appeared to be the main reason for chronic mycotic infections. In contrast, boric acid was effective in curing 98% of the patients who had previously failed to respond to the most commonly used antifungal agents and was clearly indicated as the treatment of choice for prophylaxis. PMID- 1941802 TI - Importance of locally derived birth weight nomograms. AB - Significant differences exist between the published nomograms of birth weight for gestational age. Differences in demographics, altitude above sea level and study methodology have all been implicated. A three-year experience of uncomplicated singleton gestations (N = 14,766) was analyzed for birth weight and gestational age. The mean, 10th percentile and their 95% confidence intervals were compared to Brenner's data and a pooled sample from other studies in this country. The mean birth weights were significantly higher than Brenner's after 32 weeks' gestation and higher than the pooled mean after 35. The 10th percentiles were significantly greater than Brenner's after 36 weeks' gestation. Approximately 66% of neonates at risk, below our 10th percentile, would not be identified with Brenner's criteria. We agree with Goldenberg that uniform criteria for the definition of the normal population are important in identifying aberrant growth. However, birth weight standards should be developed for the specific population in question. PMID- 1941803 TI - Epidermal thickness and skin appendage involvement in vulvar intraepithelial neoplasia. AB - Colposcopically directed biopsies obtained from 165 women with vulvar intraepithelial neoplasia (VIN) were studied to determine both the thickness of the dysplastic epithelium and the depth of involved and noninvolved skin appendages and ultimately to provide a morphometric basis for laser therapy for the condition. Multiple measurements per section were made, and the mean epithelial thickness was calculated for each biopsy. The mean (+/- SD) thickness of the epithelium for all grades of VIN was 0.52 +/- 0.23 mm, with the lesions ranging in thickness from 0.10 to 1.90 mm. The thickness of the involved epithelium varied little, regardless of the location of the lesions. The study indicated that VIN frequently is a multifocal disease most commonly affecting the central vulvar structures, with the posterior half of the vulva the area affected most often. The difference in thickness between the various grades of VIN was not of practical clinical significance from a therapeutic point of view. The measurements suggest that laser vaporization to a depth of 1.0 mm, including the zone of thermal necrosis, should be sufficient to destroy most epidermal lesions without skin appendage involvement. If the initial biopsy showed involvement of adjacent hair follicles or sebaceous glands, deeper tissue destruction would be necessary to theoretically achieve greater than 90% elimination of the disease. PMID- 1941804 TI - Merkel cell tumor in pregnancy. A case report. AB - A Merkel cell tumor occurred in a young, pregnant woman. The patient delivered prematurely, and the infant died of prematurity. The patient died within two years of the diagnosis. PMID- 1941805 TI - Tuberculous endometritis presenting as postmenopausal bleeding. A case report. AB - Genital tuberculosis presented as postmenopausal bleeding in a woman with third degree procidentia. After two months of combination antimycobacterial treatment, she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by nine months of postoperative drug therapy. PMID- 1941806 TI - Adenocarcinoma in a single horn of a bicornuate uterus. A case report. AB - Adenocarcinoma developed in one horn of a bicornuate uterus. Making such a diagnosis is difficult, and hysteroscopy is helpful. PMID- 1941807 TI - Ehlers-Danlos syndrome type III and pregnancy. A case report. AB - Ehlers-Danlos syndrome (EDS) is a heterogeneous connective tissue disorder rarely complicating pregnancy. Some types are associated with high maternal mortality, while others appear more benign. Two term, vaginally delivered pregnancies with good outcomes from one patient were managed with EDS type III. The patient experienced no significant morbidity attributable to the EDS. The only other previously reported case of EDS type III involved serious problems with joint laxity and pain morbidity, requiring preterm cesarean delivery. PMID- 1941808 TI - Submucous myomas treated with gonadotropin releasing hormone agonist and resulting in vaginal hemorrhage. A case report. AB - Gonadotropin releasing hormone agonists are often used in the management of myomas in an attempt to decrease both the myoma and uterine volume. This therapy in a woman with submucous myomas resulted in profuse vaginal bleeding requiring a transfusion and myomectomy. PMID- 1941809 TI - Markers of bone turnover in rheumatoid arthritis. PMID- 1941810 TI - Erythropoietin: a hormone finds a purpose. PMID- 1941811 TI - Oligosaccharides: an optional extra or of relevance to disease mechanisms in rheumatology? AB - I have discussed how oligosaccharides may be important to receptor ligand binding and how in some instances abnormalities can be detected in disease. Manipulating these structures offers the potential for developing novel therapeutic strategies, but perhaps more work is needed to define how subtle variations in these structures occur in normal physiology and how this relates to the pathophysiological mechanisms in disease. PMID- 1941812 TI - Synovial inflammation induced by a local allergic reaction. AB - A rat model has been developed to examine the possible role of homocytotropic antibodies in initiating or exacerbating synovial inflammation. The technique, passive synovial anaphylaxis, involves passively sensitizing rat knee joints with specific IgE, then challenging intravenously with the corresponding antigen while monitoring for signs of inflammation. Swelling of the sensitized joints reached maximum 2 h after the challenge, then gradually decreased to prechallenge levels by 24 h. Radioisotopic joint scans detected a passive synovial anaphylaxis induced increase in local blood flow and exudation within the joints. The degree of swelling correlated directly with the amount of antigen specific IgE in the sensitizing serum, and individual joints remained sensitized for up to 36 days after the IgE injection. PMID- 1941813 TI - Phenotypic characteristics of T cells interacted with synovial cells. AB - We demonstrated the phenotypic characteristics of T cells interacted with synovial fibroblast-like cells. A small percentage of peripheral blood T cells adhered to synovial fibroblast-like cells. When synovial cells were treated with interferon-gamma or interleukin-1 beta, the percentage of T cells that adhered to the treated cells markedly increased in comparison with the value for untreated synovial cells. The kinesis of T cell adherence to treated synovial cells differed from that of HLA-DR antigen expression on synovial cells. T cell adherence was not blocked by mouse monoclonal anti-HLA-DR and anti-HLA-ABC antibodies. The phenotypes of the adherent and nonadherent T cells were investigated with a flow cytometer. The CD29 + subset was more adhesive than the CD45RA + subset to IL-1 beta-stimulated synovial cells. The proportions of high density lymphocyte function associated antigen (LFA)-1 alpha and LFA-1 beta were greater in the adherent than in the nonadherent T cells, and the mean fluorescence intensities of LFA-1 alpha, LFA-1 beta and CD2 molecules on adherent T cells were significantly higher than those on nonadherent T cells. Our results support the concept that an interaction between infiltrating lymphocytes and synovial cells occurs in the synovium, resulting in the initiation and perpetuation of immune responses in synovial tissue in rheumatoid arthritis. PMID- 1941814 TI - Computed tomography of the masticatory system in rheumatoid arthritis. AB - The resolution of computed tomography (CT) allows evaluation of hard and soft tissues of the masticatory system. Eleven patients with RA were scanned by CT in direct sagittal and coronal projection because of temporomandibular joint problems. Our results indicate that in addition to bony changes there are changes in the masticatory muscles. These are detectable by CT and may be caused by the RA itself or related to impaired function. PMID- 1941815 TI - Serum osteocalcin levels in rheumatoid arthritis: a marker for accelerated bone turnover in late onset rheumatoid arthritis. AB - Levels of serum osteocalcin (OC) are increased in diseases with high bone turnover. We determined OC levels in (1) 15 patients with definite rheumatoid arthritis (RA) in early stages according to Steinbrocker's functional class FC I II, (2) 40 patients at advanced stages (FC III-IV) and (3) 17 patients with late RA (onset at age of 65 or more). Sixty-two healthy volunteers, divided into 3 subgroups corresponding to the patients, and 19 patients with primary fibromyalgia syndrome (FMS) served as controls. All patients were included in a short term as well as a longitudinal study over one year. Mean OC levels were significantly elevated in patients with late onset RA compared with healthy controls (p = 0.037), while the OC values in early RA FC I-II and advanced RA FC III-IV did not differ significantly from the corresponding control group and the patients with FMS. The late RA group showed a positive correlation between OC and the erythrocyte sedimentation rate (ESR) (r = 0.641, p = 0.007) with a significant decrease of OC (p less than 0.01) as well as ESR (p = 0.047) over one year. We conclude increased OC levels correlate with disease activity in older patients with active RA, suggesting impaired bone turnover. This finding supports the picture of heterogeneity in RA with more late onset patients displaying "high bone turnover." PMID- 1941816 TI - The clinical course of Felty's syndrome compared to matched controls. AB - In a cohort of 919 patients with definite or classic rheumatoid arthritis followed prospectively since 1966, we identified 36 patients with Felty's syndrome (FS). Their clinical course was compared to that of 72 matched controls from the same cohort. Patients with FS had more extraarticular features and more infections than control patients. The presence of joint erosions, serial Lansbury indices, and death rates were similar in both groups. Cardiovascular disease was the commonest cause of death in both groups, accounting for 32% of all deaths. Sepsis accounted for 10% of deaths in the group with FS and 13% of deaths in the controls. PMID- 1941817 TI - Recombinant human erythropoietin therapy in patients with rheumatoid arthritis with the anemia of chronic disease. AB - We treated 5 patients with rheumatoid arthritis (RA) with anemia of chronic disease with recombinant human erythropoietin (rHuEPO) for 11 weeks. An increase in hematocrit (Hct) greater than 5 was seen in 4 patients after 4 weeks of therapy. The 5th patient had a significant rise in Hct when the dosage of rHuEPO was increased to 150 units/kg from the 4th to 7th week. The subcutaneous administration of rHuEPO dose, reduced by one third with respect to initial dose, maintained an effective Hct value in all the 5 patients during the last 4 weeks of therapy. There was no change in disease activity. In one patient Hct normalization completely resolved symptoms of angina pectoris and permitted hip replacement surgery in another. No side effects occurred during rHuEPO therapy. We conclude that HuEPO is an effective, safe and well tolerated therapy for RA patients with severe anemia of chronic disease. PMID- 1941818 TI - Complications of immunosuppression associated with weekly low dose methotrexate. AB - Complications of immunosuppression are thought to be rare with the use of low dose pulse methotrexate (MTX) for nonneoplastic conditions. We describe 4 complications of immunosuppression observed in a group of 41 patients who had received MTX for at least 6 months, during a 2-year period. We report the first case of a reversible lymphoproliferative disorder similar to that reported with immunosuppressive therapy associated with organ transplantation. Two cases of disseminated herpes zoster and 1 case with Pneumocystis carinii pneumonia are described. As the indications for the use of low dose MTX broaden and older patients with other comorbid diseases are included, our experience suggests that complications of immunosuppression with prolonged use of MTX may be seen more commonly. PMID- 1941819 TI - Comparison of different methods of classifying patients with systemic lupus erythematosus. AB - The sensitivity and percent agreement of 3 methods of classifying patients with systemic lupus erythematosus (SLE), the 1982 American Rheumatism Association (ARA) revised criteria and a simple and full classification tree, were compared using data from The Johns Hopkins Lupus Cohort, a prospective study of 198 patients with SLE. The 1982 revised criteria were significantly more sensitive than the simple classification tree, correctly identifying 184 (93%) cases compared to 168 (85%) (p = 0.016). Agreement between these 2 classification schema was noted in 174 (87%) cases with 164 classified correctly and 10 failing to satisfy either criteria set. The full classification tree correctly identified 186 (94%) cases. There was no difference in the sensitivity of either the 1982 revised criteria or the full classification tree by racial group; however, the simple classification tree was significantly less sensitive among black than Caucasian patients (80 vs 91.5% p = 0.038). Our data support the continued use of the 1982 revised ARA criteria for the classification of patients with SLE for clinical and epidemiologic research studies. PMID- 1941820 TI - Infection and disease activity in systemic lupus erythematosus: a review of hospitalized patients. AB - Infection is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). A review of all SLE admissions to our hospital during a 5 year period was conducted to determine the rate and nature of infection, and its association with overall disease activity, measured by the SLE Disease Activity Index (SLEDAI). Eighty-one patients (79 women, 2 men) were admitted for a total of 2,738 days (176 admissions). There were 53 proven infections, giving an infection rate of 1.94/100 hospital days. Twenty-three (43.4%) of these were major infections (requiring IV antibiotics). Two of 3 deaths were due to septicemia. By logistic regression analysis, infection was significantly associated with disease activity (p = 0.005), but not with disease duration or prednisone dosage. Our data confirm that infection is common in hospitalized patients with SLE, is associated with overall disease activity independent of prednisone dose, and causes significant mortality. These facts should be borne in mind when hospitalization is considered for patients with SLE. PMID- 1941821 TI - Alopecia in systemic lupus erythematosus. Relation to disease manifestations. AB - Alopecia was observed in 40/74 (54%) patients with systemic lupus erythematosus (SLE). Patients with alopecia had a significantly higher rating for cutaneous manifestations, Raynaud's phenomenon and muscle tenderness, and most of these signs correlated with the magnitude of alopecia. There was no difference between patients with or without alopecia for arthritis, nephritis or central nervous system manifestations. Alopecia correlated with disease activity index but did not correlate with various specific measurements of disease exacerbation. PMID- 1941822 TI - Anticardiolipin antibodies and lupus anticoagulant in Chinese patients with systemic lupus erythematosus. AB - Ninety-one consecutive patients with systemic lupus erythematosus (SLE) were studied. Forty-two patients had positive anticardiolipin antibodies (aCl) 40 aCl IgG (44.4%); 4 aCl-IgA (4.4%); 1 aCl-IgM (1.1%). One patient had both aCl-IgG and aCl-IgA and 1 patient had aCl-IgG, aCl-IgA and aCl-IgM. Ten patients (11.1%) had lupus anticoagulant (LA). Both aCl isotypes and LA had no statistical association with thrombosis or thrombocytopenia. PMID- 1941823 TI - A prospective evaluation of antithyroid antibody prevalence in 100 patients with systemic lupus erythematosus. AB - During a 6-month period, 100 patients with systemic lupus erythematosus (SLE) were consecutively studied for the presence of antithyroid antibodies and thyroid disease. Overall, the prevalence of antithyroid antibodies was similar in patients with SLE (21%) and controls (16%). However, antithyroglobulin antibodies were found in 11% of patients with SLE and only 2% of controls (p = 0.009). The levels of antimicrosomal antibodies were also different (median levels: SLE = 400; controls = 100) but this difference did not reach statistical significance. We found a significant correlation between thyroid stimulating hormone (TSH) levels and the levels of both the antithyroglobulin dilutions (p less than 0.05) and the antimicrosomal dilutions (p less than 0.05). This was not seen in the controls. A higher frequency of clinical thyroid disease was seen in patients with SLE with thyroid antibodies (5/21; 3 hypothyroid, 2 hyperthyroid) than in those without these antibodies (1/79; p = 0.001). Levels of antithyroid antibodies correlated with clinical or subclinical (marked by elevations of TSH) thyroid disease. Patients with SLE with these antibodies were significantly older (mean age 47.5 +/- 13 years) than those without antithyroid antibodies (mean age 37.5 +/- 12 years; p less than 0.001). Antithyroid antibodies define a subset of older patients with SLE with increased prevalence of both clinical and subclinical thyroid disease. PMID- 1941824 TI - The role of antineutrophil cytoplasm antibodies, anticardiolipin antibodies, von Willebrand factor antigen, and fibronectin for the diagnosis of systemic vasculitis. AB - Autoantibodies directed against cytoplasmic components of neutrophil granulocytes and monocytes (c-ANCA) are a disease specific marker for Wegner's granulomatosis (WG). Autoantibodies against cardiolipin (aCl) are specific for a subgroup of autoimmune disorders, which can also be associated with systemic vasculitis. Fibronectin (Fn) and von Willebrand factor antigen (vWfAg) are produced by blood vessel endothelial cells in response to injury. We tested sera of 61 patients with various types of systemic vasculitides, sera of 13 patients with retinal vasculitis, and sera of 199 patients with rheumatic diseases for c-ANCA, aCl, Fn, and vWfAg. c-ANCA was positive in 14/17 patients with WG, and 2/4 with polyarteritis nodosa (PAN). No serum from healthy donors or patients with other vasculitic or rheumatic diseases was positive for c-ANCA. Moreover, we found aCl, Fn, and vWfAg significantly elevated in almost all patients with vasculitic syndromes. Therefore, we consider c-ANCA a marker, specific for the diagnosis of WG or PAN, whereas aCl, Fn, and vWfAg are nonspecific but sensitive markers of vascular damage. PMID- 1941825 TI - Chromosome aberration in lymphocytes from Behcet's disease. AB - Peripheral lymphocytes from 14 patients with Behcet's disease (BD) were examined for frequencies of chromosomal aberration. The frequency of gaps and breaks were not high in patients with BD but the frequency of dicentrics was increased in patients treated with colchicine or anticancer medicines. Patients treated with neither colchicine nor anticancer medicines showed no increased frequency of dicentrics. Our data suggested that the effect of treatment with colchicine or anticancer medication was one of the causes of the chromosome aberration observed in some BD lymphocytes. No numerical abnormality was observed in BD lymphocytes. PMID- 1941826 TI - Study of magnetic resonance imaging in transient osteoporosis of the hip. AB - To better define the magnetic resonance imaging (MRI) features during transient osteoporosis of the hip, we carried out sequential MRI of 8 patients with transient osteoporosis of the hip showing the typical radiographic pattern of diffuse osteoporosis of the femoral head. These cases displayed the same MRI changes in the femoral head and neck characterized by low signal intensity on the T1 weighted images and high signal intensity on the T2 weighted images. The MRI signal became normal within 11 months, but surprisingly, migration of the MRI abnormalities was observed during the course of the disease in 5 cases: abnormal MRI signals were first observed in the anterior area, then migrated to the posterior part, while a normal MRI signal reappeared in the anterior part. We conclude that MRI seems to show some particular features in transient osteoporosis of the hip, which normalize after a few months of evolution; this could represent a migration of MRI abnormalities. Such findings could help in the differential diagnosis of hip diseases such as aseptic bone necrosis. PMID- 1941827 TI - Factors associated with radiographic osteoarthritis: results from the population study 70-year-old people in Goteborg. AB - Selected factors potentially associated with radiographic osteoarthritis (OA) were studied in 2 subsamples of 79-year-olds, within the longitudinal prospective study 70-year-old People in Goteborg. A very significant (p less than 0.01 in men, p less than 0.001 in women) association was found between radiographic knee OA and body mass index (BMI), and a significant (p less than 0.05) association was also observed between radiographic hand OA and BMI in men. Smoking correlated negatively (p less than 0.01) to radiographic knee OA in both sexes, even after adjusting for BMI. Other factors, including diabetes, ischemic heart disease, hypertension, physical activity, education, vocational training, marital status, serum uric acid, triglycerides, cholesterol and blood glucose levels did not correlate to radiographic OA. Finally, no correlation was found between either decreased bone mineral content or the presence of previous fragility fractures. PMID- 1941828 TI - Flexion angles of the knee in different resting positions and their relation to the prevalence of osteoarthritis. AB - The effect of different resting postures on the loading profile of the knee in 1,155 subjects was studied. The recent change to chair sitting has radically modified this profile, resulting in an increase in midflexion loading and virtual disuse of full flexion of knee and hip. Domestic activities do not compensate for this underutilization. There is consistent evidence from 7 communities that the prevalence of osteoarthritis of the hip is substantially lower in communities that do not habitually chair-sit. No other adequate explanation for this difference has been identified. These findings suggest a need to reexamine the incomplete use hypothesis. PMID- 1941829 TI - Tendinous and ligamentous hyperlaxity in patients receiving longterm hemodialysis. AB - Chronic renal insufficiency gives rise to osteoarticular and tendinous alterations, with tendinous rupture reaching 3.6% among patients receiving hemodialysis. To evaluate potential tendinous and ligamentous alterations, 39 consecutive patients receiving longterm hemodialysis (mean dialysis time 33 months) were studied prospectively by clinicoradiological methods. Of the 39 cases, atlantoaxial subluxation was found in 3 (7.7%). Tendinous or ligamentous hyperlaxity was present in 29 (74%) with patellar tendon elongation in 19 (49%), articular hypermobility in 20 (51%) and both in 10. Differences were significant (p less than 0.05) in patients with articular hypermobility with over 36 months' dialysis, and even more so (p less than 0.01) in those with over 48 months. Atlantoaxial subluxation was more frequent after 48 months' dialysis. Therefore, patients receiving longterm hemodialysis are prone to present tendinous or ligamentous hyperlaxity with atlantoaxial subluxation as well. PMID- 1941830 TI - The misdiagnosis of gout and hyperuricemia. AB - Of 9,108 consecutive new patients seen in an outpatient rheumatology clinic, 155 (1.7%) were diagnosed as having gout. But 164 (1.8%) had been incorrectly diagnosed as having gout in the community. Misdiagnosis was more likely in those with psoriatic arthritis (odds ratio 3.841, 1.944-7.590) and pseudogout (odds ratio 4.152, 2.422-7.119) and less common in patients with nonspecific arthralgias (odds ratio 0.536, 0.326-0.881). Seventy-six percent of incorrectly diagnosed patients received allopurinol while slightly more than 15% were treated with uricosuric agents. PMID- 1941831 TI - Estimation of bone mineral density in children with juvenile rheumatoid arthritis. AB - Bone mineral content of different areas of the skeleton was measured by dual photon absorptiometry in 20 children with juvenile rheumatoid arthritis (JRA) and compared to 20 age and sex matched healthy children. Spinal density was similar in both groups in prepubertal children but decreased in the postpubertal girls with JRA. Total bone density was also decreased in the postpubertal girls. Six children with JRA had repeat scans 12 to 24 months later; in 3 children total bone mineral content increased significantly with an intensive management program. Our study suggests that bone mineral density does not show a pubertal increase in children with JRA, as it does in healthy children. PMID- 1941832 TI - Auranofin therapy for juvenile rheumatoid arthritis: results of the five-year open label extension trial. AB - Eighty-eight children with juvenile rheumatoid arthritis (JRA) who completed a double blind, randomized placebo controlled trial of oral gold were entered into an open label extension phase during which they received auranofin (AF) at a dosage of 0.15-0.2 mg/kg/day (9 mg/day maximum). Eleven (12.5%) patients completed 5 years of AF therapy; 77 (87.5%) did not. Fifteen (17%) of the 88 were in disease remission at the final visit. Mean duration of therapy for those who discontinued was 646 days. Parental/patient decision and insufficient therapeutic effect were the 2 most frequent reasons for early termination, followed by adverse effects. Though relatively well tolerated, AF provides adequate longterm management for only a small percentage of patients with JRA. PMID- 1941833 TI - Disseminated Nocardia brasiliensis infection: an unusual complication of immunosuppressive treatment for childhood dermatomyositis. AB - The use of steroids combined with cytotoxic drugs has increased in the last decade. The concomitant increase of opportunistic infections has contributed significantly to morbidity and mortality of patients treated with immunosuppressive agents. We describe a child with dermatomyositis who developed disseminated Nocardia brasiliensis infection while receiving steroids and methotrexate. Infectious etiology was established by gram stain. The patient was treated successfully. Disseminated Nocardia brasiliensis infection is rare with a high reported mortality. Diagnosis may be delayed secondary to insidious onset, similarity of clinical manifestations to other pathogens and slow growth in routine culture media. Nocardia should be considered early in the evaluation of infection in patients treated with immunosuppressive agents. PMID- 1941834 TI - Rheumatoid-like arthritis in a lion tailed macaque. AB - Very few satisfactory models of rheumatoid arthritis (RA) exist in nonhuman species. It is particularly striking that nonhuman primates have only rarely been described to have disease processes resembling classic RA seen in humans. We describe the case of a lion tailed macaque (Macaca silenus), housed at the National Zoological Park in Washington DC, that had a polyarticular inflammatory arthropathy resembling RA. Gross and histopathologic examination of necropsy tissues and radiographic findings strongly suggest a rheumatoid-like disease, never before described in this species. PMID- 1941835 TI - Gold induced hepatitis and pure red cell aplasia. Complete recovery after corticosteroid and N-acetylcysteine therapy. AB - A 54-year-old man developed severe cholestatic jaundice and pure red cell aplasia shortly after beginning treatment with gold sodium thiomalate. Although the hepatic toxicity began to spontaneously improve, the pure red cell aplasia was progressive. Treatment with prednisone and N-acetylcysteine (NAC) infusions was followed by prompt and complete hematologic recovery. Gold induced pure red cell aplasia should be added to the list of gold induced hematologic toxicities that can be potentially reversed with NAC infusion therapy. PMID- 1941836 TI - Pneumocystis carinii pneumonia associated with methotrexate therapy in rheumatoid arthritis. AB - Opportunistic infections occur in patients with rheumatic diseases treated with low dose methotrexate (MTX) with or without other immunosuppressants. Our case report illustrates a fatal case of Pneumocystis carinii pneumonia in a patient with rheumatoid arthritis treated with low dose MTX and glucocorticoid. A review of the literature reveals other opportunistic infections such as Cryptococcus, Nocardia, and herpes zoster presenting in such patients. These occurrences suggest that MTX should be used cautiously in patients with rheumatic disease receiving concomitant medical therapy. PMID- 1941837 TI - Low dose methotrexate therapy for rheumatoid arthritis complicated by pancytopenia and Pneumocystis carinii pneumonia. AB - In a patient with rheumatoid arthritis pancytopenia and Pneumocystis carinii pneumonia occurred during low dose methotrexate therapy. This case emphasizes the potential development of opportunistic infections even with low dose methotrexate. Pneumocystis carinii pneumonia resembles methotrexate induced pneumonitis. Therefore opportunistic infections should be considered before a definite diagnosis of methotrexate induced pneumonitis is made. PMID- 1941838 TI - Remitting, seronegative (A) symmetrical synovitis with pitting edema--two cases of RS3PE syndrome. AB - The sparing effect of neurological damage on the development and progression of several arthritic conditions has been documented. We describe the first 2 cases of unilateral remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in individuals with neurologic disorders. Case 1 suffered from birth trauma resulting in paresis of the right upper extremity and developed RS3PE syndrome in the nonaffected extremities. Case 2 developed RS3PE syndrome on the nonparetic side 7 years after a cerebrovascular accident resulting in hemiparesis. PMID- 1941839 TI - Red blood cell susceptibility to lipid peroxidation, membrane lipid composition and antioxidant enzymes in patients with rheumatoid arthritis. PMID- 1941840 TI - Ankylosing spondylitis with exuberant sclerosis in the sacroiliac joints, symphysis pubis and spine. PMID- 1941841 TI - IgM class immunoglobulin with high rheumatoid factor activity interferes with the measurement of interleukin 1 beta. PMID- 1941842 TI - Reliability and reproducibility of visual analogue scale and numeric rating scale for therapeutic evaluation of pain in rheumatic patients. PMID- 1941843 TI - Osteonecrosis in a patient receiving longterm hemodialysis. PMID- 1941844 TI - Tuberculosis of the pubis symphysis. PMID- 1941845 TI - Polymyositis and myelodysplastic syndrome. PMID- 1941846 TI - The genetics of rheumatic fever: relationship to streptococcal infection and autoimmune disease. AB - A large body of evidence suggests that patients with rheumatic fever immunologically respond abnormally both at a humoral and cellular level to streptococcal antigens cross-reactive with mammalian tissues. Implicit in this concept is that this abnormal immune response is genetically programmed. Using a monoclonal antibody called D8/17, a B cell marker has now been identified in 90 100% of all patients with rheumatic fever tested in 5 different geographical and ethnic populations. This trait appears to be inherited in an autosomal recessive fashion. This recognition of a B cell marker unique to individuals with rheumatic fever has important public health implications with respect to identification of individuals susceptible to rheumatic fever, possible prevention of disease and the recognition of prime candidates for future streptococcal vaccines. PMID- 1941847 TI - Host-parasite interaction in the pathogenesis of rheumatic fever. AB - Recent investigation has delineated some of the bacterial and host factors that may play a role in the pathogenesis of rheumatic fever. Continuing studies support the role of antibodies to crossreactive antigens in human tissues and the group A streptococcal cell in inducing tissue damage associated with this disease. Several specific epitopes have now been defined that are common to the crossreactive antigens. Data from recent outbreaks of rheumatic fever in the USA suggest that mucoid group A streptococcal strains, belonging to serotypes M1, M3, M5, M6 and M18 may have accounted for these outbreaks. While these strains are thought to be rheumatogenic, the exact characteristic(s) that renders them so is yet to be determined. PMID- 1941848 TI - Leg ulcers. PMID- 1941849 TI - Healing and medicine. PMID- 1941850 TI - The pathogenesis of migraine. PMID- 1941851 TI - Patients' views on how to run hospital outpatient clinics. AB - To investigate patients' views and expectations when attending outpatient clinics a questionnaire-based study was performed. The questionnaires asked about appointment systems, continuity of care, staff appearance, chaperons and medical students. Patients wanted fixed appointment times, to see the same doctor on successive visits, for the staff to be formally dressed and to have chaperons during examination. The number of medical students should be restricted especially for women patients. Staff should be sensitive to patients' needs. PMID- 1941852 TI - Treatment of basal cell carcinoma with intralesional interferon alpha-2b. AB - We report a series of 11 basal cell carcinomas of various types treated with nine intra-lesional injections of 1.5 million units of interferon alpha-2b. The diagnosis was confirmed histologically in each case. After 3 months' follow-up six tumours had resolved both clinically and histologically. In three cases the tumour size was reduced. One tumour grew larger. Side effects were well tolerated except by one subject who was withdrawn. Those cases which responded have now been followed-up for between 12 and 26 months with no clinical or histological evidence of tumour recurrence. This is the longest period of follow-up so far reported for this novel treatment. The results are encouraging and, if maintained in future series, may indicate a useful role for interferon alpha in the management of this common cutaneous malignancy. PMID- 1941853 TI - Asymptomatic hypothyroidism and hypercholesterolaemia. AB - Hypothyroidism is a cause of secondary hyperlipidaemia. This study investigates the frequency of biochemically diagnosed hypothyroidism and its relationship with plasma cholesterol concentration in apparently healthy people. Thyroid function tests (total T4, TSH, and free T4) were performed on 272 apparently healthy men and women (179 vegetarians, 93 meat eaters) with a plasma cholesterol concentration above 7 mmol/l and on 90 individuals with a plasma cholesterol below 4.1 mmol/l who were matched for age, sex and dietary habits. Six per cent of those with a plasma cholesterol above 7 mmol/l had biochemical evidence of hypothyroidism as defined by a TSH greater than 10 mIU/l (reference range 1-6) and a low free T4 below 10 pmol/l (reference range 10.1-25). Eighty per cent of these people had a high titre of thyroid anti-microsomal antibodies. Of the 90 individuals with a plasma cholesterol level below 4.1 and the 25 randomly selected participants none had biochemical evidence of hypothyroidism. Hypothyroidism is relatively common in apparently healthy people with a raised plasma cholesterol. It appears no commoner in vegetarians than in meat eaters. PMID- 1941854 TI - Pregnancy and drug addiction--long-term consequences. AB - With the prevalence of drug addiction amongst young women rising in the United Kingdom the problems associated with pregnancy in this group are increasingly being reported. An attempt has been made to determine whether the birth of a baby is a sufficient stimulus for the mother to cease her drug of addiction. Between the years 1966 and 1988, 86 such mothers gave birth at St Mary's Hospital, London, whom we were able to trace for at least one year after their last delivery. The results show that the majority of mothers continued with their drug use and where this is so the chances of the child remaining with her are markedly reduced. Discussion centres around possible ways of identifying those likely to succeed in drug withdrawal during pregnancy and the need for increasing and continued support for these mothers and their babies after they have left hospital. PMID- 1941855 TI - Venous thromboembolic disease in uncemented total hip replacement surgery--a one year follow-up of 490 patients. AB - A retrospective study of the morbidity and mortality from deep vein thrombosis (DVT) and pulmonary embolus (PE) in 490 consecutive patients undergoing uncemented total hip replacement was carried out in a district general hospital. Special diagnostic tests for DVT and PE were not available. Patients were followed up for one year. There were three deaths in hospital and eight further deaths during the first year, all unrelated to DVT and PE. The clinical incidence of venous thromboembolism was 2.04%. While clinical diagnosis of venous thromboembolic disease probably underestimates its incidence, the figures for mortality are accurate. With every patient accounted for one year after operation, there were no deaths attributable to PE in this series. PMID- 1941856 TI - Is the non-pharmacological treatment of hypertension neglected? AB - Non-pharmacological techniques in the management of hypertension have been shown to be beneficial. This pilot study was set up to examine how often routine advice was given with respect to weight reduction and/or lifestyle adjustments, and whether it was needed. Three-quarters of the 69 patients in the study smoked or were overweight but only half of the smokers recalled advice to stop. One-fifth of the patients were apparently not told to lose weight. Only one-third recalled being told to reduce alcohol intake. Lifestyle counselling and the management of hypertension in this small study appeared to be not completely effective for various reasons. It is likely to be cheaper and more satisfactory than medication alone or as an adjunct and its application deserves further study. PMID- 1941857 TI - Levels of visual impairment in a day centre for people with a mental handicap. AB - A prospective study screening for visual impairment in a day centre for people with a mental handicap showed that 30% required spectacles or registration as blind or partially-sighted and a further 20% had previously unknown pathology. Carers were not reliable in identifying visual problems in their charges, and routine screening should be encouraged. High Street optometrists should be able to measure visual acuity in the individuals in this sample excluding those cared for in special care units for whom screening may be less beneficial. PMID- 1941858 TI - Screening siblings for glaucoma in the UK. AB - The current practice and ideals of ophthalmologists when alerting and screening siblings at risk of chronic simple glaucoma were assessed by means of a questionnaire. Seventy-nine per cent of Trent Region consultants responded, and of these, 18% do not attempt to alert siblings of glaucoma sufferers. Those who do rely on the probands to alert their siblings and the high street optometrists to screen. Under more favourable conditions, all respondents would advise screening for siblings over 40 years of age. Fifty-nine per cent would then advocate the letter as the optimum method of communication and 78% would prefer that an ophthalmologist screen this high risk group. In a pilot study of a hospital-based screening service, siblings living within a 15 mile radius of the hospital were invited by letter to attend for screening. Ninety per cent attended, of whom 12.5% required treatment and a further 11% careful observation. The cost of detecting a case of treatable disease by this strategy was estimated at 138 pounds. PMID- 1941859 TI - Variations in the prevalence of spondylolysis in early British populations. AB - Crude prevalence rates of spondylolysis were estimated in skeletal populations from various periods. There was a steady increase in prevalence from 3.74% in Romano-British to 5.08% in medieval populations, but the rate fell considerably to 1.42% in a population from an 18th/19th century context. This trend was not statistically significant, however. The male/female ratio was approximately unity until the 18th/19th century when the expected male excess appeared. The lesions predominantly affected L5 and all were isthmic in type. Of the total of 52 cases, only four were unilateral. One occurred in the fourth cervical vertebra. There were few complications; spondylolisthesis was noted in four cases and in three there were osteoarthritic changes on the superior margin of the displaced lamina. PMID- 1941860 TI - Abdominal surgery in war--the early story. PMID- 1941861 TI - Antiphospholipid syndrome and acute adrenal insufficiency. PMID- 1941862 TI - Successful retransplantation of the heart and lungs in an adult with cystic fibrosis. PMID- 1941863 TI - Paracoccidioidomycosis granuloma simulating posterior fossa tumour. PMID- 1941864 TI - Complete fracture of urethral Foley's catheter: a rare complication. PMID- 1941865 TI - Treatment of colonic anastomotic strictures with 'through the scope' balloon dilators. PMID- 1941866 TI - Accident proneness and illness proneness. PMID- 1941867 TI - Arthur Conan Doyle. PMID- 1941868 TI - von Munchhausen and his syndrome. PMID- 1941869 TI - Management of hypertension. PMID- 1941870 TI - Blood transfusion and AIDS in the USA. AB - We have examined data for 3518 cases of transfusion-acquired AIDS (TA-AIDS) onsets as reported to the USA Centers for Disease Control (CDC) through 30 June 1990. We discarded 1077 of these records because of missing or uncertain date of infection. We present here infection and onset data on the remaining 2441 cases in a Rees Plot of year of onset vs. year of infection. This is probably the only class of AIDS patients for whom the date of infection is reasonably ascertainable. Also the large number of cases which we present, by cohorts of year of infection, should be useful for epidemiology and for public health planning purposes. PMID- 1941871 TI - Elderly patients and the National Health Service. PMID- 1941872 TI - Provision and awareness of first aid in five luxury hotels in Cardiff. PMID- 1941873 TI - Playground injuries: a scientific appraisal of popular concerns. AB - The widespread public concern in Britain over childhood injuries arising from playground accidents is examined using a new national data base on leisure accidents managed by the Department of Trade and Industry. Popular beliefs about the level of risk, the nature and cause of injury, and remedial measures are found to be unsupported by the analysis. Playground risks are comparatively low; accident causes are diverse and most involve long bone injuries and not head injuries as has been widely reported; and the cost of some popular risk reduction measures would seem to be incommensurate with the reasonably-anticipated risk reduction which they might afford. It is suggested that for those who wish to reduce risk further, consideration should be given to increasing public awareness of the many causes of risk, of the opportunities which the individual has to control risk, and of the inevitability of residual risk. PMID- 1941874 TI - The umbilical cord: normal parameters. AB - The average length of the umbilical cord is 50-60 cm in the normal full term newborn infant. The length of the cord is an index of foetal activity and is dependent on the tension caused by the freely moving foetus, primarily during the second trimester. The short cord is associated with foetal akinesis or maldevelopment of the central nervous system and is a significant early marker of developmental abnormalities including Down syndrome. Abnormal girth of the cord should make one suspicious of a patent urachus or an umbilical hernia and caution should be used before clamping. The importance of the twist is that, if not present, one should suspect congenital anomalies. The twist should be to the left or counter clockwise. The cord stump separates from the baby at about two weeks of age at present in the era of triple dye care with a large variability due to multiple factors. PMID- 1941875 TI - Systemic treatment of breast cancer. PMID- 1941876 TI - The way out of special hospital. PMID- 1941877 TI - Pharmaceutical services to the mentally ill. AB - This paper provides an overview of the pharmaceutical services to the mentally ill within the community, the District General Hospital, Psychiatric Hospital, Regional Secure Unit, Special Hospital and Prison. With an overall picture of underfunding and underprovision a number of models of service are proposed for the future. PMID- 1941878 TI - The role of the police at major incidents. PMID- 1941879 TI - The role of the UK ambulance service in major incidents. PMID- 1941880 TI - Physiopharmacological approach to mechanical factors of hypertension in the atherosclerotic process. AB - Hypertension may influence the atherosclerotic process of large arteries via pressure and shear forces. The pressure force dilates and stiffens arteries because of the non-linear elastic behaviour of arterial walls. This partly explains the increased diameter and decreased compliance of the brachial artery in hypertensive subjects compared with normotensive controls. However, pressure lowering by antihypertensive drugs does not always reverse large artery alterations indicating that other mechanisms are involved. Reversal of low compliance obtained with certain antihypertensive drugs is generally concomitant with large artery vasodilation, suggesting that smooth muscle relaxation plays a major role in the compliance response to drugs. Atherosclerosis associated with hypertension also causes additional loss of compliance and creates a vicious circle of sclerosis development by accelerating the biophysical fatigue of bioelastomers. Hypertension may contribute to atherogenesis by means of wall shear stress which is the frictional force exerted by the circulating blood column on the intima of arteries. Since it is likely that atherosis lesions may develop preferentially in low shear conditions, hypertension may promote the haemodynamic conditions of atherogenesis at the blood-wall interface. The response of wall shear to antihypertensive treatment is not unequivocal. For example, the beta-blocker, atenolol, does not change shear whereas carteolol increases shear rate and stress and these effects are closely related to change in platelet-free calcium concentration. This finding is consistent with the effect of shear forces on cell permeability to calcium demonstrated in vitro and points to the crucial role of wall shear as a biophysical signal capable of modifying the endothelial structure and function of arteries. PMID- 1941881 TI - Hypertension and atherosclerotic (ischaemic) heart disease. AB - Epidemiological surveys show the clear association of hypertension with an increased risk of developing ischaemic heart disease. One method of quantifying atherosclerosis is to measure, at necropsy, the percentage of the intimal surface of the coronary arteries or aorta which is occupied by raised plaques. When this is done in a large number of subjects the amount of intimal involvement in any particular geographical population correlates directly with the frequency of ischaemic heart disease. In all these populations, whether at a high risk or low risk of developing ischaemic heart disease, hypertensive subjects have a greater intimal involvement by plaques than normotensive subjects. Thus, the increased risk in hypertension is, in part, mediated by possession of more plaques. Plaque growth is due to the accumulation of lipid from the plasma, the ingress of monocytes with their conversion to lipid filled foam cells and the formation of collagen by smooth muscle cells. Hypertension may act by altering endothelial function to potentiate all these processes. Mechanical stress on endothelial cells will evoke the formation of growth factors for smooth muscle cells. Plaque growth in man is also episodic due to the formation of thrombi; a proportion of these episodes are symptomatic producing acute myocardial ischaemia but the majority are silent leading to sudden plaque expansion. Thrombi over plaques are either due to endothelial denudation injury or more commonly due to the tearing of the cap of a plaque leading to deep intimal injury. Necropsy surveys of control populations show that subjects with hypertension have a greater frequency of recent plaque tears compared with normotensive subjects. PMID- 1941882 TI - Changes in vascular morphology in essential hypertension. AB - Hypertension has emerged as an important risk factor in cardiovascular diseases. However, the success of antihypertensive treatment in reducing cardiac mortality is limited. It is becoming clear that structural changes in the resistance vessels and, indeed, other vascular changes such as hypertrophy in the aorta and left ventricle increase the risk of premature cardiac events. Future therapy for hypertension must be directed at not only lowering blood pressure but also reversing structural alterations in the vasculature. PMID- 1941883 TI - Magnetic resonance imaging: a method for the assessment of changes in vascular structure and function. AB - A brief review is made of the history of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). The advantages and disadvantages of MRI are discussed with particular reference to methods of studying the vascular system. Techniques developed to study separately sclerosis and atherosis, the two components of atherosclerotic disease, are discussed in more detail. Finally, in vitro and in vivo results are presented to demonstrate the great wealth of information already available from the NMR signal and hence its considerable potential for the study of vascular disease in the future. PMID- 1941884 TI - Structural changes during the early onset of experimental hypertension: trophic influences of the renin-angiotensin system. AB - All forms of established hypertension are characterised by hypertrophy of the heart and blood vessels. Although these structural alterations are a normal adaptation to raised blood pressure, it has been suggested that hypertrophy may develop by a mechanism independent of pressure. Some investigators claim that in the young spontaneously hypertensive rat, hypertrophy of the blood vessels and heart is present at a time before the rise in pressure. Evidence also exists to support the role of angiotensin II in directly influencing growth within the vasculature. The present study confirms that hypertrophy of the mesenteric resistance vessels is present in the 3-week old spontaneously hypertensive rat. However, enhanced vascular structure was also associated with a higher mean arterial blood pressure. No increase in activity of the renin-angiotensin system could be detected. These observations raise doubts as to whether hypertrophy of the blood vessels can develop independently of raised pressure. PMID- 1941885 TI - Use of the cardiopulmonary flow index to evaluate cardiac function in thoroughbred horses. AB - The ratio of the cardiopulmonary blood volume to stroke volume is called the cardiopulmonary flow index (CPFI). The CPFI can be determined indirectly from the simultaneous recording of a radiocardiogram and an electrocardiogram. The CPFI and cardiac output were measured simultaneously in horses (n = 10) that were diagnosed as having cardiac disease. The diseased subjects were probably all exposed to feed contaminated with the ionophore, salinomycin, and all showed clinical signs indicative of chronic toxic myocarditis. The results obtained from these subjects were compared with those from control animals and significant differences (P less than 0.05) were found between the mean CPFI of the control horses and those with macroscopically visible myocardial fibrosis on post mortem examination. No significant differences were found between the means of the cardiac output measured in either of the groups of horses. The effect of pharmacological acceleration of the heart rate on the CPFI was also studied. Significant differences (P less than 0.05) were found between the mean CPFI and the slopes of the regression lines of CPFI on heart rate of the control and principal groups of horses. These differences were greatest at heart rates near to the resting heart rates of the individuals. The CPFI was found to be a more sensitive measure of cardiac function than cardiac output, in the horses. PMID- 1941886 TI - The ammonia tolerance test in horses. AB - Clinically normal horses (n = 8) with ages ranging from 5 to 8 years, were starved for 12 h and their plasma ammonia concentrations were measured. The mean fasting plasma ammonia concentration was 17.8 +/- 3.8 mumol l-1. After dosing ammonium chloride at a dose rate of 0.02 g kg-1, there was a significant increase in plasma ammonia concentration, with a maximum rise after 20 min (P less than 0.05). To investigate the influence of temperature on plasma ammonia concentrations of stored samples, 8 plasma samples were stored at -20 degrees C and 4 degrees C respectively. The plasma ammonia concentrations were measured after 6, 12 and 24 h in each of the stored samples. Plasma ammonia concentrations increased significantly after 12 and 24 h when stored at 4 degrees C (P less than 0.05). When plasma was stored at -20 degrees C there was no significant increase from baseline concentrations during 24h (P greater than 0.05). PMID- 1941887 TI - The pathology of subclinical infection of Encephalitozoon cuniculi in canine dams producing pups with overt encephalitozoonosis. AB - The macroscopic, microscopic and clinical pathology and the serology of 2 clinically normal Staffordshire Bull Terrier bitches, both of whom produced pups with confirmed encephalitozoonosis, is described. Mild histopathological changes, similar to those seen in the infected pups, were observed. The spores of Encephalitozoon cuniculi were seen in the renal tubules of the kidney of one of the bitches. The serum urea concentrations of one of the bitches was elevated. A positive titre against E. cuniculi was obtained in both of the bitches. A 10-year old girl who had had close contact with one of the infected litters of pups, seroconverted to E. cuniculi. Her two siblings were serologically negative. PMID- 1941888 TI - The safety of dimetridazole alone and in conjunction with oxytetracycline in Hereford crossbred steers. AB - Dimetridazole was given intraruminally alone, and in conjunction with oxytetracycline to healthy, 10-11 month-old Hereford cross-bred steers (n = 6). Intraruminal treatment with dimetridazole was given through a fistula at 75 mg kg 1 daily for 5 d, while the oxytetracycline was injected intramuscularly at 10 mg kg-1 on Days 1 and 3 of the dimetridazole treatment. The animals were observed at various intervals throughout the trial period for adverse reactions, including effects on ruminal activity and motility, changes in live-mass, venous acid-base balance, haematology and ruminal and serum ammonia concentrations. Dimetridazole, either when used alone or in conjunction with oxytetracycline, had a marked effect on ruminal function. Within 6 h of dosing, the ruminal pH fell to below 5, but then returned to pretreatment values over the next 24-48 h. This was followed by the eradication of the ruminal protozoal population in all animals tested and an increase in the methylene blue reduction time to more than 6 min. Ruminal motility remained unaffected throughout this period. During the week of treatment, the mean live-mass of the animals dropped by 20 +/- 9.9 kg in the dimetridazole treated group and by 13.3 +/- 2.8 kg in the animals treated with both dimetridazole and oxytetracycline. A mild to severe watery diarrhoea, which continued for 1 to 2 d, occurred in 4 animals after the first dimetridazole treatment. A compensated metabolic acidosis and an increase in haematocrit were observed. An initial transient rapid rise in rumen ammonia concentrations did not result in a concurrent rise in serum ammonia concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941889 TI - Hereditary laminitis in Jersey calves in Zimbabwe. AB - The clinical signs and radiological findings of a rare laminitis-like condition in Jersey calves (n = 6) are described. Regular hoof-trimming proved very beneficial. Pedigree studies of the affected calves strongly suggest a recessive autosomal inheritance. PMID- 1941890 TI - A craniopharyngioma in a seven-year-old dog. AB - A seven-year-old male Border Collie was presented with a history of lethargy, episodic circling, incoordination and polydypsia. Physical examination revealed depression, obesity and bradycardia. A neurological examination indicated the possible presence of a space-occupying lesion in the brain. Results of the clinical investigation revealed hyposthenuria, sinus bradycardia and increased concentration of protein in the cerebrospinal fluid. A computerised axial tomography scan revealed a mass in the region of the hypophysis. The dog was euthanased and a post mortem examination confirmed the presence of a craniopharyngioma. PMID- 1941891 TI - Molluscum contagiosum in three horses. AB - Suspected molluscum contagiosum was diagnosed in 3 horses in the Chingola district of Zambia. The horses were found to be suffering from a slow progressive skin disease with lesions on the chest, shoulders, inner and lateral aspects of the fore- and hindlimbs, the face, fetlocks, pasterns and on the lateral surfaces of the body. The lesions varied from 4 to 20mm in diameter, were hairless but covered by soft keratin projections which, when removed, left a raw elevated base tightly adherent to the epidermis. These lesions bled profusely when the animals were groomed. Older lesions were well circumscribed, raised above the surface, devoid of hair and after removal of grey-white keratin flakes, had a depigmented waxy appearance. Microscopically cytoplasmic inclusions containing many pox virions were found. Attempts at culturing the virus were unsuccessful. PMID- 1941892 TI - Molluscum contagiosum in a horse. AB - An adult stallion presented with a severe papular dermatitis of especially the neck, chest and genitalia. A marked scrotal oedema was present. Histopathological examination of skin biopsies, revealed the presence of numerous intracytoplasmic molluscum bodies in areas of focal epidermal hyperplasia. Electron microscopical examination showed the presence of typical pox virions in affected epidermal cells. Attempts at viral isolation were unsuccessful. This is believed to be the first reported case of molluscum contagiosum in a horse in the Republic of South Africa. PMID- 1941893 TI - Chylothorax in a kitten. AB - Chylothorax with collapse of the lungs was found on postmortem examination of a 2 week-old Siamese kitten. The chylothorax was probably due to a lack of continuity of the thoracic duct. PMID- 1941894 TI - Cobalt deficiency in pastured sheep in the south-western Cape Province. AB - Annually recurrent illthrift and mortalities in a small flock of pastured sheep at the Regional Veterinary Laboratory, Stellenbosch were cured by the supplementation of cobalt. The similarities between acute cobalt deficiency and ovine white liver disease are discussed. PMID- 1941895 TI - Perinatal lamb mortality--its investigation, causes and control. AB - Methods of investigating perinatal loss in grazing sheep flocks are reviewed and evaluated. The "wet-dry" method is the simplest method for assessing minimal prevalence, whereas the differences between the numbers of single and twin foetuses present at ultrasonic determination of litter size during pregnancy, and the numbers of single and twin lambs present at lamb-marking, is the most precise. The veterinary investigation of field mortality involves full autopsy of a representative sample of dead lambs, a history of prenatal nutrition, disease and husbandry, as well as a qualitative estimate of weather conditions over the period of lamb collection. Pathological processes may be identified in over 95% of deaths and the specific cause determined in about 75% of deaths. The identification of the specific causes in the remainder of deaths, all classified as the starvation-mismothering-exposure (SME) complex, requires intensive, costly, on-site observation, and physiological and biochemical assessment. The probable causes of these deaths include prenatal physiological handicaps resulting from placental insufficiency, aberrant parent-offspring behaviour, management-induced mismothering, misadventure, inadequate milk supply or teat and udder abnormalities, and cold-induced starvation. The gross pathology and pathophysiology of birth stress and the SME complex, which are associated with at least 80% of mortality, are summarised. Birth injury to the foetal central nervous system, characterised by cranial and spinal meningeal haemorrhage is exclusive to parturient deaths and the SME complex. Observed flock prevalences range from 81% to 100% in parturient deaths, and 20% to 57% in the SME complex. The high total prevalence and experimental evidence, indicate the major causal role of birth stress in the pathogenesis of these entities. Lethal congenital malformations, infections (both congenital and acquired after birth), trace element deficiencies and predation are reviewed as minor causes. The new understanding of the pathogenesis of perinatal lamb mortality, recognises the heritable nature of birth mass, maternal pelvic dimensions, parent-offspring behaviour, and the resistance of neonates to cold. Control measures need to incorporate selection for maternal rearing ability, further refinement of prenatal nutritional management of twin-bearing ewes, disease control, provision of shelter for lambing flocks, and avoidance of husbandry practices which frustrate innate parent-offspring behaviour. A selection programme is summarised. PMID- 1941896 TI - Evidence for stimulated glutathione synthesis by phenobarbital pretreatment during an oxidative challenge in isolated hepatocytes. AB - Hepatocytes isolated from phenobarbital-pretreated and naive male Sprague-Dawley rats were preincubated with 80 microM N, N-bis (2-chloroethyl)-N-nitrosourea and subsequently exposed to varying concentrations of menadione. We observed that the reduced glutathione levels of the hepatocytes isolated from the sodium phenobarbital(PB)-pretreated, but not the naive rats, recovered to near-control levels after exposure to 200 microM menadione. Since this recovery occurred in the presence of N, N-bis (2-chloroethyl)-N-nitrosourea (an inhibitor of glutathione reductase), we hypothesized that this represented a PB-mediated increase in de novo synthesis of glutathione. To test this hypothesis and to further assess the possible contribution of glutathione reductase in the recovery of the glutathione levels, we preincubated hepatocytes isolated from PB pretreated and naive rats with 2 mM buthionine sulfoximine, with or without N, N bis (2-chloroethyl)-N-nitrosourea. Following exposure to menadione, samples were periodically removed for glutathione assessment. Consistent with our hypothesis, the addition of buthionine sulfoximine abrogated the ability of the PB-pretreated hepatocytes to restore glutathione levels following a menadione challenge. Buthionine sulfoximine in combination with N, N-bis (2-chloroethyl)-N-nitrosourea completely abolished hepatocellular glutathione homeostasis for all of the concentrations of menadione employed. The findings from this investigation underscore the importance of phenobarbital-mediated increases in glutathione synthesis, as well as the enhanced levels of glutathione reductase, in maintaining the pool of reduced glutathione and ultimately mitigating the consequences of oxidative stress. In addition, these findings suggest that PB pretreatment increases the reserve capacity of the hepatocyte for glutathione synthesis via a hitherto undescribed hormetic mechanism, a reserve expressed fully only on an oxidative stress of sufficient magnitude. PMID- 1941897 TI - Studies on the mechanism of haloacetonitrile-induced gastrointestinal toxicity: interaction of dibromoacetonitrile with glutathione and glutathione-S-transferase in rats. AB - The haloacetonitrile, dibromoacetonitrile (DBAN), is a direct-acting genotoxic agent that has been detected in drinking water. In a time course study, male Sprague-Dawley rats were treated with DBAN (75 mg/kg PO), and killed at 0.5, 1, 2, and 4 hr after treatment. In a dose response study, animals were treated orally with various doses of DBAN (25, 50, 75, and 100 mg/kg) and killed at one half hour after treatment. Control animals received 1 ml/kg PO of the vehicle dimethyl sulfoxide (DMSO). In both experiments blood and organs were collected and stored at -80 degrees C until the time of analysis. At 0.5 hr after treatment, a single oral dose of DBAN caused a significant decrease of glutathione (GSH) concentrations in liver (54% of control) and stomach (6% of control). Hepatic GSH depletion was maximal at 0.5 hr and rebound to the control levels by 4 hr. In contrast, gastric GSH concentrations remained low at all time points. DBAN caused an insignificant change in both kidney and blood GSH levels. DBAN significantly inhibited glutathione-S-transferase (GST) activity in liver and stomach. Hepatic GST inhibition was maximal (34% of control) at 2 hr and minimal (80% of control) at 4 hr. Meanwhile, in the stomach GST activity was inhibited at 1 hr (60% of control) and remained low at all times after treatment. Both GSH depletion and GST inhibition were dose-dependent. This study indicates that GSH and GST play an important role in the metabolism and detoxification of DBAN in rats. The prolonged depletion of GSH and inhibition of GST in the gastrointestinal (GI) tissues suggest that the GI tract is a major target for DBAN toxicity. PMID- 1941899 TI - Effects of isoflurane on the DNase I activity in an isolated enzyme preparation and on the DNase I-G actin complex. AB - Effects of isoflurane on the DNase I activity in an isolated enzyme preparation and in the DNase I-globular (G) actin complex were investigated. DNase I, DNase I G actin complex, and G actin were exposed to various (0.2-4.0 vol%) isoflurane concentrations for 180 min. Thereafter, DNase I activity was determined. DNase I activity was inhibited in relation to time and concentration of isoflurane exposure. At concentrations ranging from 0.2 to 1.0 vol% of isoflurane inactive DNase I was activated in the DNase I-G actin complex. The DNase I inhibitor G actin showed a reduced capability to inhibit DNase I following isoflurane exposure. Albumin can inhibit the DNase I inactivation possibly by competition in the reactions between DNase I/albumin and isoflurane. After exposure to isoflurane the absorption maximum of DNase I was identical with the absorption maximum of heat-denatured DNase I. The results suggest a mechanism by which isoflurane may affect DNA in an indirect way at concentrations to which the patient is exposed during clinical anesthesia. PMID- 1941898 TI - Drug-metabolizing enzymes in liver, olfactory, and respiratory epithelium of cattle. AB - The drug-metabolizing enzymes of olfactory and respiratory epithelium of cattle were determined. The data of nasal tissues were compared to those of bovine liver. Both oxidative and nonoxidative enzyme activities were investigated. Many compounds including testosterone were used as substrates for the P450-dependent monooxygenase activities. The results demonstrated that the P450 content and all the activities assayed including reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P450 reductase were much higher in the olfactory than in the respiratory mucosa and for some activities (hexamethyl-phosphoramide and dimethylnitrosamine N-demethylase, aniline hydroxylase, and ethoxycoumarin O deethylase) the values in the olfactory tissue were even markedly higher than those of liver. Also the activities of some nonoxidative enzymes such as glutathione S-transferase, uridine 5'-diphosphate (UDP)-glucuronyl-transferase, and epoxide hydrolase were higher in the olfactory than in the respiratory mucosa but lower than in liver. The results taken together suggest that the olfactory and respiratory epithelium of cattle, which contain in addition to a wide array of nonoxidative enzymes multiple forms of P450, can be useful and easily available tissues to study the biotransformation processes of odorants. PMID- 1941901 TI - Glutathione S-transferase-catalyzed conjugation of 9,10-epoxystearic acid with glutathione. AB - The possible role of glutathione S-transferases (GST) in detoxification of fatty acid epoxides generated during lipid peroxidation has been evaluated. Present studies showed that cytosolic human glutathione S-transferases belonging to alpha, mu, and pi classes isolated from human liver and lung catalyzed the conjugation of glutathione and 9,10-epoxystearic acid. The product of enzymatic reaction, i.e., conjugate of GSH and epoxystearic acid, was isolated and characterized. The Michaelis constant (Km) values of the alpha, mu, and pi classes of GSTs for 9,10-epoxystearic acid were found to be 0.47, 0.32 and 0.80 mM, respectively, whereas the maximal velocity (V max) values for the alpha, mu, and pi classes of GSTs were found to be 142, 256, and 52 mol/min/mol, respectively. These results indicate that even though 9,10-epoxystearic acid is a substrate for all the three classes of GSTs, the mu class isozymes have maximum activity toward this substrate and may preferentially metabolize fatty acid epoxides more effectively as compared to the other classes of GSTs. PMID- 1941900 TI - Characterization of covalent binding of [14C]-2-chloro-4-acetotoluidide to microsomes of starling liver and kidney. AB - In this study, we have characterized the covalent binding of [14C]-2-chloro-4 acetotoluidide (CAT) radioactivity to microsomes of starling liver and kidney. The maximal velocity (Vmax) of covalent binding and apparent Michaelis constant (Km) for both tissues were similar. The Vmax for liver and kidney were 52.8 and 68.9 pmol/min/mg protein, and the apparent Kms were 0.54 and 0.87 mM, respectively. The covalent binding of radioactivity to heat-denatured microsomes of liver and kidney was reduced by 62% and 15%, respectively. Incubation at 0 degrees C reduced the binding by 80% to liver and 70% to kidney microsomes. Absence of nicotinamide adenine dinucleotide phosphate (NADP) and molecular O2 reduced the binding to liver microsomes by 36 and 53%, as opposed to 28% increase and 26% decrease in binding to kidney microsomes, respectively. Inducers of cytochrome P450 monooxygenase (P450), phenobarbital, and 3-methylcholanthrene (3 MC), had opposite effects on the covalent binding of [14C]-CAT radioactivity to hepatic and renal microsomes. Phenobarbital increased the binding to hepatic microsomes by 100% and had no effect on binding to renal microsomes. 3-MC, on the other hand, increased the binding to kidney microsomes by threefold and had no effect on the binding to hepatic microsomes. SKF 525A, an inhibitor of P450, inhibited the binding to hepatic microsomes by 60% at 0.5 mM but failed to have any effect on binding to renal microsomes. alpha-Naphthoflavone, another inhibitor of P450, had no effect on the covalent binding of [14C]-CAT radioactivity to microsomes of either tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941902 TI - Effect of different amino acidic pretreatments that protect the kidney against papillary necrosis induced by bromoethylamine on differential distribution of renal nonprotein sulfhydryls. AB - Content of nonprotein sulfhydryls (NPSH) was found to be higher in rat renal cortex than in external medulla and papilla. Administration of bromoethylamine (BEA), at a dose that produces extensive papillary necrosis and minor effects in the other renal segments, induced a significant reduction in NPSH levels of renal cortex and external medulla, with no changes in the papilla. Treatment with N acetyl-L-cysteine (NAC) elicited an increase in papillary NPSH and a decrease in the cortex, with opposite changes being observed with an amino acid mixture of glutamine, glycine, and cystine (AM). Similar results were found in animals pretreated with NAC or AM prior to BEA intoxication. These pretreatments protect the cortex, external medulla, and papilla from the necrosis induced by BEA. It is suggested that protection of BEA-induced renal necrosis by NAC or AM pretreatments might be due to different mechanisms, with NPSH playing direct or indirect roles, respectively. PMID- 1941903 TI - Tissue distribution, metabolism, and elimination of perfluorooctanoic acid in male and female rats. AB - The elimination, tissue distribution, and metabolism of [1-14C]perfluorooctanoic acid (PFOA) was examined in male and female rats for 28 days after a single ip dose (9.4 mumol/kg, 4 mg/kg). A sex difference in urinary elimination of PFOA derived 14C was observed. Female rats eliminated PFOA-derived radioactivity rapidly in the urine with 91% of the dose being excreted in the first 24 hr. In the same period, male rats eliminated only 6% of the administered 14C in the urine. The sex-related difference in urinary elimination resulted in the observed difference in the whole-body elimination half-life (t1/2) of PFOA in males (t1/2 = 15 days) and females (t1/2 less than 1 day). Analysis of PFOA-derived 14C in tissues showed that the liver and plasma of male rats and the liver, plasma, and kidney of female rats were the primary tissues of distribution. The relatively high concentration of PFOA in the male liver was further examined using an in situ nonrecirculating liver perfusion technique. It was shown that 11% of the PFOA infused was extracted by the liver in a single pass. The ability of the liver to eliminate PFOA into bile was examined in rats whose renal pedicles were ligated to alleviate sex differences in the urinary excretion of PFOA. In a 6-hr period following IP administration of PFOA, there was no apparent difference in biliary excretion, where both males and females eliminated less than 1% of the PFOA dose via this route. We hypothesized that the sex difference in the persistence of PFOA was due to a more rapid formation of a PFOA-containing lipid (i.e., a PFOA-containing mono-, di-, or triacylglycerol, cholesteryl ester, methyl ester, or phospholipid) in the male rat. Also, the increased urinary elimination of PFOA in females may have been due to increased metabolism to a PFOA-glucuronide or sulfate ester. However, no evidence that PFOA is conjugated to form a persistent hybrid lipid was obtained, nor were polar metabolites of PFOA in urine or bile detected. In addition, daily urinary excretion of fluoride in male and female rats before or after PFOA treatment were similar, suggesting that the parent compound is not defluorinated. Thus, the more rapid elimination of PFOA from female rats is not due to formation of a PFOA metabolite. PMID- 1941904 TI - Effect of ascorbic acid esters on hepatic glutathione levels in mice treated with a hepatotoxic dose of acetaminophen. AB - Acetaminophen (APAP) with or without ascorbyl stearate (AS) or ascorbyl palmitate (AP) was administered by gavage to male Swiss-Webster mice at a dose of 600 mg/kg for each chemical. The biochemical markers of hepatotoxicity, serum transaminases (serum glutamate pyruvate transaminase [SGPT], serum glutamate oxaloacetic transaminase [SGOT]) and serum isocitrate dehydrogenase (SICD) activities were monitored after APAP and APAP + AP or AS dosing. There were significant reductions in serum transaminase and SICD activities in the APAP- + ascorbate ester-treated animals as compared to APAP-positive controls. Oral coadministration of APAP with AP or AS did not prevent the initial hepatic GSH depletion (15 min-4 hr postdosing). However, hepatic GSH content began to rise in the APAP + AS or AP-treated animals at 4 hr and reached control values within 12 hr postdosing. Urinary mercapturate conjugates were also significantly higher in the APAP + AP or AS-treated animals as compared to APAP alone when measured over a 60-min postdosing period. Plasma sulfobromophthalein (BSP) retention was approximately eight times higher in APAP-treated animals as compared to the APAP + ascorbate ester treatments indicating maintenance of hepatic excretory functions in presence of AP or AS. Prior depletion of hepatic GSH by diethyl maleate (DEM) did not alter hepatoprotective effects of AP or AS in the presence of APAP. Hepatic ascorbate levels also peaked at 4 hours after APAP + AP or AS treatments. The possible role of L-ascorbic acid esters in GSH regeneration following co-administration of a hepatotoxic dose and APAP is discussed. PMID- 1941906 TI - Nutritional value of yeast for Dermatophagoides pteronyssinus (Acari: Epidermoptidae) and the antigenic and allergenic composition of extracts during extended culturing. AB - Cultures of European house dust mite, Dermatophagoides pteronyssinus (Trouessart), were evaluated with respect to yeast nutritional value, together with an assessment of the antigenic and allergenic composition. CIE analysis of extracts illustrated that yeast contributes many antigens throughout the rearing period. However, there is an indication of the consumption of only one particular yeast antigen by the mites. Total protein content profile of the mite cultures is shown in addition to the total allergen activity (RAST determinations). The allergenic activity of the extracts steadily increased during the mite culturing period; this may be due to the accumulation of fecal particles containing the major allergen. PMID- 1941905 TI - Temporal variation in morphological and genetic characteristics within a hybrid population of Culex pipiens (Diptera: Culicidae). AB - Samples of mosquitoes in the Culex pipiens L. complex from Memphis, Tenn., were collected from June to November 1985 and examined in regard to allozyme frequencies and ratios of the two arms of the phallosome of the male genitalia (DV/D). The dominant allozymes of hexokinase (HkA) and 6-phosphogluconate dehydrogenase (PgdF) significantly increased in frequency during this period as did the mean DV/D ratio. An analysis of gene frequencies by species group designated by DV/D ratios revealed no significant differences among Cx. pipiens, Cx. quinquefasciatus Say, and intermediates. The lack of association of gene frequencies with the taxa determined by the DV/D ratio indicated that although allozyme frequencies were correlated temporally with the DV/D ratio in the population, they were not associated with subspecies. These results are consistent with previous work that has shown latitudinal association and thermal stability differences in the major allozymes of these enzymes in the Cx. pipiens complex. PMID- 1941907 TI - Populations of Phlebotomus papatasi (Diptera: Psychodidae) and the risk of Leishmania major transmission in three Jordan Valley habitats. AB - The abundance, population structure, and Leishmania infection rates of Phlebotomus papatasi were studied at two villages, a 10-yr old date plantation, and an undisturbed natural habitat in the Jordan Valley throughout one season. On 109 trap nights in the villages, 53 female and 61 male P. papatasi were caught, whereas in burrows in the natural and agriculturally modified habitat, greater than 3,500 sandflies were trapped on 157 trap nights. Burrows in the data plantation produced larger numbers of males and females significantly more frequently than burrows in the natural habitat. The sex ratio in the natural habitat and the date plantation was significantly male biased. Parous rates were similar among habitats, whereas gravid females were significantly more active in the modified habitat. Leishmania infected females were not collected in the villages, yet close to 10% of females collected in the two other habitats were infected. Risk of transmission to humans in the villages was negligible, but people working in the date plantation were exposed to Leishmania infected sandflies. PMID- 1941908 TI - Aedes taeniorhynchus (Diptera: Culicidae) oviposition patterns in a Florida mangrove forest. AB - The association of Aedes taeniorhynchus eggs and several variables was studied in a Florida mangrove forest. Eggs were limited to stands of red mangrove (Rhizophora mangle L.) that were embedded within a black mangrove (Avicennia germinans L.) forest. The occurrence of eggs was related significantly to elevation and the amount of detritus. Field and laboratory studies indicated that grazing on black mangrove detritus by the snail Melampus coffeus L. may have limited detritus accumulation and soil organic content, thus restricting mosquito oviposition to the red mangrove stands. Eggshells were concentrated in the same habitat as eggs, suggesting that eggshells may be used to identify oviposition patterns. PMID- 1941909 TI - Effects of ivermectin (MK-933) on the reproductive rate of Aedes aegypti (Diptera: Culicidae). AB - Aedes aegypti (L.) females were blood fed a single time on rabbits previously injected subcutaneously with ivermectin at 10 or 50 times the labeled dose recommended for cattle (0.2 mg [AI]/kg body weight). Although adult mosquito survival was unchanged by the low dose, fecundity and hatch were depressed slightly. Females fed on rabbits at the high dose exhibited reduced survival and egg production compared with females fed on control rabbits. Eggs from these females also were less likely to hatch, and subsequent larval survival was lower than controls. The effect of ivermectin on these reproductive parameters diminished as the time between drug administration and blood meal increased. PMID- 1941910 TI - Effects of juvenile hormone and its analogs on vitellogenin synthesis and ovarian development in Ornithodoros moubata (Acari: Argasidae). AB - Effects of juvenile hormones (JH) and JH analogs on the release of vitellogenin (Vg) into the hemolymph and ovarian development in unfed adult female ticks, Ornithodoros moubata (Murray), were investigated. Topical application of acetone solvent and injection of acetone or oils showed some increase in Vg titer in the hemolymph. Topical application of JH (JH I, JH II, JH III) and JH analogs (methoprene, S21149, S21150, and S31183) dissolved in acetone to unengorged adult females elevated Vg titer in the hemolymph but only to the same level as the acetone controls. These effects were independent of dose. Injection of JH (JH I, JH II, JH III) and methoprene dissolved in mineral oil also did not significantly increase the Vg titer in the hemolymph compared with the controls (mineral oil injection). Electrophoretic analysis of hemolymph from females 5 d after treatment topically or by injection with JH and JH analogs showed faint Vg bands which comigrated with Vg's (Vg-1 and Vg-2) of normal, engorged female hemolymph, but Vg bands were detected more clearly in the hemolymph samples that were collected greater than 2 wk after treatment. However, the same level of Vg also was detected in the hemolymph of females treated with acetone or mineral oil. Vg synthesis in females treated with JH and JH analogs was analyzed by in vivo labeling and fluorography, which showed that Vg synthesis was not induced by application of JH to unengorged females. PMID- 1941911 TI - Sensitive developmental period of last-instar German cockroaches (Dictyoptera: Blattelidae) to fenoxycarb and hydroprene. AB - The sensitive developmental period of last-instar German cockroaches, Blattella germanica (L.), to topical applications (10 micrograms/microliters) of fenoxycarb and hydroprene was determined. Developmental duration of last instars treated with fenoxycarb on days 1, 3, or 6 was 9-11 d longer than the development of nymphs treated with hydroprene or acetone. In addition, fenoxycarb caused mortality in 59% of the nymphs treated on day 6. A high level of wing twisting and sterility was observed among female and male cockroaches treated with fenoxycarb or hydroprene on days 1, 3, or 6 of the last stadium. Nymphal production by adults treated with juvenoids on day 9 of the last stadium (3-4 d before eclosion) was not affected. Our findings show that the sensitive developmental period for juvenoid-induced effects in last-instar B. germanica is limited to the first half of the stadium. PMID- 1941912 TI - Analysis of inheritance of oral susceptibility of Aedes aegypti (Diptera: Culicidae) to dengue-2 virus using isofemale lines. AB - Isofemale lines were compared to determine possible genetic variation in oral susceptibility within the Fare strain of Aedes aegypti (L.) to dengue-2 (DEN-2) virus. Three groups of 12 isofemale lines each were tested statistically using the SAS CATMOD procedure of analysis of variance. The "isofemale line" effect was highly significant, demonstrating genetic variability in oral susceptibility among females. The length of time eggs were stored before hatching influenced the oral susceptibility of the adult mosquitoes for DEN-2 review. PMID- 1941913 TI - Influence of larval and adult nutrition on biting persistence in Aedes aegypti (Diptera: Culicidae). AB - Biting persistence was measured for Aedes aegypti (L.) mosquitoes given different levels of larval and adult nutrition. Persistence was measured as the total number of times during a 60-min trial that a mosquito returned to land on a defensive host after being disturbed and dislocated from the host, and as the rate of decline of landings over the 60 min test (pattern of persistence). Large females were significantly more persistent than smaller females, regardless of whether the females were provided water or 5% sucrose for 3 d before the test. Access to sucrose for 3 or 7 d did not influence the total number of landings of large females. Large females starved for 7 d exhibited significantly reduced persistence compared with large females starved for only 3 d. Water-fed specimens displayed a more rapid decline in the pattern of persistence than sucrose-fed specimens. Field-collected females, intermediate in size between the large and small laboratory females, had dry weights indicating they were relatively starved. They had a total number of landings similar to the small laboratory females and a persistence pattern similar to sucrose-fed specimens. Size-related differences in persistence may be one factor causing differences in parity rates and vector potential observed between large and small females in Ae. aegypti field populations. PMID- 1941914 TI - ELISA for identification of blood meal source in black flies (Diptera: Simuliidae). AB - A modified ELISA, in which a biotinylated second antibody and a streptavidin biotinylated peroxidase complex are used, has been developed to identify the blood meal sources of black flies. The modified assay is sensitive enough to identify correctly 100% of blood meals at 73 h postingestion and 80% of blood meals at 116 h postingestion in black flies held in the field at ambient temperatures. PMID- 1941915 TI - Plasmodium species identification by ELISA for sporozoites removed from dried dissection slides. AB - This study tested the feasibility of identifying salavary gland sporozoites to species by Plasmodium falciparum ELISA by drying them on slides or in vials. The glands were dissected from Anopheles gambiae Giles s.l. and An. funestus Giles collected in western Kenya. In 119 gland infections containing a geometric mean of 1,222 sporozoites, a mean of 72.5% of sporozoites were removed in 60 microliters saline from slides at the time of dissection. Each of the 119 samples was divided into three 18 microliters aliquots. Subsamples were stored at -70 degrees C, dried in vials, or dried on a microslide. When tested by Plasmodium falciparum ELISA, positive reactions were observed in 86.6% of frozen samples, 70.6% of samples held dry in vials, and 50.4% of samples held dry on microslides for 1 mo. Of 90 gland infections where coverslips were removed and slides were left to dry for 1 mo before adding blocking buffer, 81.1% were positive for P. falciparum. This was not significantly different from either frozen gland samples (where 85.5% of 392 infections were identified or frozen gland plus corresponding thorax samples where 86.2% of 160 samples were identified). In malaria field studies, where it is not always practical to freeze samples, sporozoites from dissected mosquitoes can be preserved adequately for ELISA identification by simply removing coverslips and drying dissection slides. PMID- 1941916 TI - Evaluation of host-targeted acaricide for reducing risk of Lyme disease in southern New York state. AB - A 2-yr evaluation of a commercial product designed to reduce the risk of Lyme disease by delivering permethrin-treated cotton to white-footed mice (Peromyscus leucopus) was conducted at three sites in Westchester County, N.Y., an area where Lyme disease is endemic. We examined the numbers of host-seeking nymphal Ixodes dammini Spielman, Clifford, Piesman & Corwin, the numbers of larval I. dammini infesting mice, and the proportion of nymphs infected with Borrelia burgdorferi, the causative agent of Lyme disease. The density of nymphs collected by drag sampling did not differ between treatment and control areas in the first year for either a woodland or recreational site. In the second year, no significant decrease in the density of nymphs was observed in the treatment areas compared with the control areas. Numbers of larvae on 67 mice captured on treatment and control grids did not differ for woodland and recreational sites, but significantly fewer larvae were found on mice captured at the residential treatment site. The percentage of host-seeking ticks infected with spirochetes did not differ between treatment and control sites in any habitat for either year. The use of permethrin-treated cotton did not measurably reduce the numbers of I. dammini or the proportion of ticks infected with spirochetes at our study sites. PMID- 1941917 TI - Selective breeding for photoperiodically induced developmental diapause in laboratory strains of Amblyomma americanum (Acari: Ixodidae). AB - Offspring of Amblyomma americanum (L.) reared for four generations in a 12:12 (L:D) photoperiod in the laboratory were held in 10:14 (L:D) conditions and bred to select for developmental diapause (DIA) or nondiapause (NON) characteristics for two additional generations. Sequential generations of fed DIA nymphs had mean molting times (days from detachment to ecdysis) that were 8.0% (DIA1) and 35.7% (DIA2) greater than parental ticks, and maximal development time was extended by 20% in DIA2 ticks over that of parentals. Selection in NON strains resulted in a significant decrease of detachment to ecdysis times in NON1 ticks, but the detachment to ecdysis times in NON2 ticks increased and was not different from parental ticks. Breeding for DIA and NON extremes did not affect the ability of either strain to develop rapidly if held in long-light (14:10 [L:D]) conditions. Selection for DIA resulted in extension of the period from detachment of fed nymphs to preapolysial posturing rather than from posturing to ecdysis of adults. PMID- 1941918 TI - Monitoring Culex tritaeniorhynchus (Diptera: Culicidae) abundance in cow sheds by in situ counting. AB - The number of Culex tritaeniorhynchus Giles counted in situ on five sheets of paper was compared with that of mosquitoes captured in a Nozawa blacklight trap at two cow sheds in Tsu City, Japan, to evaluate the effectiveness of the in situ counting method. The total number of Cx. tritaeniorhynchus collected on 27 lighttrap-nights (434,362) was greater than that counted in situ on 270 paper samples (18,093). A highly significant temporal correlation (Kendall's tau = 0.54) was shown between the numbers of Cx. tritaeniorhynchus collected per light trap night and per paper sample. PMID- 1941919 TI - Myiasis in a wounded soldier returning from Panama. AB - An imported case of traumatic myiasis occurred in a soldier wounded during military action in Panama in December 1989 and evacuated to Brooke Army Medical Center, Fort Sam Houston, Texas. At the medical center, five larvae were removed from the scalp wound, reared to the adult stage, and identified as Cochliomyia hominivorax (Coquerel). Though this was the only reported case of wound myiasis of the 254 servicemen evacuated for medical treatment, this incident indicates a potential mechanism for the reintroduction of C. hominivorax into the United States. PMID- 1941920 TI - Mechanisms of host-tick contact with special reference to Amblyomma americanum (Acari: Ixodidae) in beef cattle forage areas. AB - At least five groups of parameters regulate contact between ticks and host animals. Group 1 (seasonal effects) and group 2 (daily effects) comprise abiotic parameters and include daylength, temperature, relative humidity, and interactions thereof. Groups 3, 4, and 5 consist of biotic parameters. These pertain to biological processes in ticks (group 3), such as hunger responses and spatial patterns in aphagous tick populations; biological processes in host animals (group 4), such as patterns of habitat use by host animals; and interactions between host animals and ticks (group 5). Host-tick contact is possible when ticks are hungry, when ticks exhibit a positive appetence response, and when ticks and host animals are together in time and space. A descriptive model is proposed to correlate these processes and interactions with the observed behavior of the host-tick contact system in nature. Emphasis in the model is placed on host activity and differences among host types. PMID- 1941921 TI - Flies as forensic indicators. AB - Synanthropic flies, particularly calliphorids, are initiators of carrion decomposition and, as such, are the primary and most accurate forensic indicators of time of death. The relevant biology and forensic applications of the egg, larva, pupa, and young adult are discussed for various species, with emphasis on thermal history and age markers. PMID- 1941922 TI - Preliminary account of the phenology of some Nigerian savanna phlebotomine sandflies (Diptera: Psychodidae). AB - A total of 1,705 sandflies was collected by sticky trap from the Guinea savanna of northern Nigeria to determine their seasonal and spatial fluctuations in abundance. Adult sandflies persisted throughout the year, but the highest diversity and abundance were recorded at the end of the rainy season. Females were collected more frequently than were males. The species collected in order of decreasing abundance were Sergentomyia antennata Newstead, S. bedfordi Newstead, S. africana Newstead, S. schwetzi Adler, Theodor & Parrot, S. affinis Theodor, S. adleri Theodor, S. clydei Sinton, S. simillima Newstead, S. buxtoni Theodor, S. christophersi Sinton, and Phlebotomus rodhaini Parrot. Sandfly abundance was greater near rocky terrain (Dumbi inselberg) and on an animal farm than on the open plains and in a residential area. Known vectors of leishmaniasis were not collected, despite the report of human cases in the study area. PMID- 1941923 TI - Behavior of larval Aedes triseriatus (Diptera: Culicidae). AB - The behavior of Aedes triseriatus (Say) fourth instars was studied in laboratory microcosms. A list of 14 larval behaviors was developed from observations of 108 larvae performing 1,836 different acts, and a time budget was developed from 88 larvae by recording the proportion of time each larva spent in the different behavioral states. Larval behavior was organized into clusters of surface and subsurface activities, linked by "dive" and "rise" behaviors. Eight behaviors formed the major activity pattern for larvae and dominated the time budget. Feeding behavior consisted of suspension feeding, feeding at the air-water interface, brushing container and leaf surfaces, and chewing leaf veins. Most (90.8%) of the time budget was devoted to feeding, and larvae spent 52.5% of their time feeding at or near the surface of the water and 37.5% brushing while submerged. When feeding at the air-water interface, larvae rotated about the axis formed by the respiratory siphon in alternating clockwise and counterclockwise directions, possibly to rest the muscles used to twist the larval body into the U shaped posture characterizing this feeding behavior. Our studies showed that Ae. triseriatus larvae were not exclusively brushers nor bottom feeders as has been assumed for many Aedes larvae but showed great flexibility in feeding, where nearly the entire habitat was the "feeding zone." PMID- 1941924 TI - Annotated list of ticks (Acari: Ixodidae, Argasidae) reported in Peru: distribution, hosts, and bibliography. AB - A literature review and compilation of the tick specimens found in Peru and now held in the National Tick Collection was carried out to develop a working list of the tick species likely to be found in Peru. Evidence of 44 species (29 Ixodidae, 15 Argasidae), was found; representatives of 40 species are held as reference specimens. This report adds 14 species to the previously published list. PMID- 1941925 TI - Transmission of a spotted fever group rickettsia by Amblyomma hebraeum (Acari: Ixodidae). AB - Amblyomma hebraeum, a cattle tick common in southern Africa, was demonstrated to be capable of maintaining an infection with an unclassified spotted fever group rickettsia both transtadially and transovarially. All feeding stages of the tick transmitted the infection to rabbits. The rickettsia was isolated and found to be serotypically distinct from three strains of Rickettsia conorii by microimmunofluorescence. Rabbit serum titers were found to be higher with indirect fluorescent antibody (IFA) tests using the Amblyomma isolate than with those using a commercially available IFA test for R. conorii. PMID- 1941926 TI - Transmission of a newly recognized virus (Bunyaviridae, Bunyavirus) isolated from Aedes albopictus (Diptera: Culicidae) in Potosi, Missouri. AB - Aedes albopictus (Skuse) mosquitoes collected in Potosi, Mo., were tested for their ability to transmit a newly recognized Bunyamwera sero group virus isolated from the same mosquito population. Mosquitoes were fed artificial blood meals containing 4.5-6.2 log10 TCID50 of virus per ml. After 7-29 d at 25 degrees C, 79 99% of the mosquitoes had disseminated infections and 0-26% transmitted virus to fluid-filled capillary tubes. Transmission was first observed after 7 d of extrinsic incubation. Tests failed to detect transovarial transmission in 5,145 progeny from ovarian cycles 2-4. Following parenteral inoculation with 5.3-6.0 log10 TCID50 of virus, four of nine adult hamsters developed viremia. Ten of 16 suckling mice died following intracerebral inoculation of 5.0 log10 TCID50 of virus (fifth Vero cell passage); the average survival time was 8.8 d (SD, 3.5). No mortality occurred in 10 suckling mice inoculated with 3.6 log10 TCID50 of virus (second Vero cell passage). PMID- 1941928 TI - Evaluation of Australian Mesocyclops (Cyclopoida: Cyclopidae) for mosquito control. AB - Six of seven species of Mesocyclops copepods, collected from northeastern Australia, showed potential as biological control agents of Aedes mosquitoes. Methods of laboratory evaluation included predation trials at different larval mosquito densities, population growth rates at different temperatures, and laboratory cage simulations. The predation efficacy of Mesocyclops aspericornis, M. australiensis, and M. mb1 from southern Queensland, and M. darwini, M. mb2, M. notius and M. mb3 from northern Queensland were compared with M. aspericornis (used successfully in French Polynesia) against laboratory populations of Aedes aegypti (L.), Culex quinquefasciatus Say, and Anopheles farauti Laveran (No. 1). M. aspericornis (L. Kurwongbah) proved to be the most effective Queensland predator and exhibited an elevated reproductive rate at 20-25 degrees C. M. darwini was less efficient as a predator but was more fecund at 25-35 degrees C. Based on these evaluations, M. aspericornis (L. Kurwongbah) has been selected for small-scale field trials in Queensland. PMID- 1941927 TI - Effectiveness of host-targeted permethrin in the control of Ixodes dammini (Acari: Ixodidae) AB - Tubes of commercially available permethrin-treated cotton balls were distributed twice each year in 1989 and 1990 at five sites in a Lyme disease endemic area in Connecticut. Five additional sites were not treated. At each application, 48 tubes, sufficient to treat 0.4 ha, were dispersed at 10-m intervals through woodlands, around ornamental plantings, and along rockwalls. The cotton was collected by white-footed mice (Peromyscus leucopus) from the majority of the tubes, which resulted in a decrease (37.2% in 1989 and 91.5% in 1990) in the number of subadult Ixodes dammini Spielman, Clifford, Piesman, and Corwin on the mice in the treated areas. There were no significant decreases in the number of host-seeking nymphs or adults of I. dammini in 1989 or 1990 between the treated and untreated sites. The rates of infection in the host-seeking nymphs with Borrelia burgdorferi, the etiological agent of Lyme disease, at the treated sites (13.0 and 14.6% for 1989 and 1990, respectively) were comparable to those at the untreated sites (16.9 and 13.2% for 1989 and 1990, respectively). The distribution of permethrin-treated cotton around individual residences significantly reduced the number of ticks on P. leucopus but was not sufficient to reduce the risk of exposure to infected host-seeking nymphs and adults of I. dammini after two seasons of treatment. PMID- 1941929 TI - Effectiveness of selected granular acaricide formulations in suppressing populations of Ixodes dammini (Acari: Ixodidae): short-term control of nymphs and larvae. AB - Applications of selected granular acaricide formulations to the shrub layer of forested habitats during the peak activity periods of Ixodes dammini Spielman, Clifford, Piesman & Corwin nymphs and larvae significantly reduced the abundance of these stages on Peromyscus leucopus. The granules effectively penetrated growing vegetation and suppressed populations of subadult ticks questing in the leaf litter. The use of granular acaricide formulations provides the only documented method of control of free-living I. dammini nymphs and larvae in dense vegetation. As such, this technique will serve as a major component of any integrated control program against this vector tick species. PMID- 1941930 TI - Tick (Acari: Ixodidae) infestations on Zebu cattle in western Kenya: seasonal dynamics of four species of ticks on traditionally managed cattle. AB - A study was conducted on the population dynamics of four tick species infesting livestock on Rusinga Island. Infestations of Rhipicephalus appendiculatus Neumann, Rhipicephalus evertsi evertsi Neumann, Amblyomma variegatum (F.)., and Boophilus decoloratus (Koch) were monitored on East African shorthorn Zebu cattle at monthly intervals for 2 yr. These cattle were of unimproved stock under traditional husbandry without any tick control practices. Most ticks were on cattle between September and March, with a peak in December-February. Following the onset of the rainy season in April, tick numbers on the cattle declined markedly; this decline continued until July or August, when numbers started to increase again. No significant correlation could be made between these population changes and any of the four climatic factors recorded. Instead, there was a notable relationship between tick population changes and local farming practice. The area and duration of cattle grazing activity were severely curtailed during the cropping season from April to September, which reduced tick-host contact and thus the tick burdens of the cattle at that time. PMID- 1941931 TI - Ribosomal DNA structure in Aedes mosquitoes (Diptera: Culicidae) and their cell lines. AB - The molecular organization of the ribosomal DNA repeat unit in laboratory colonies of Aedes albopictus (Skuse) and Aedes aegypti (L.) and in continuous cell lines derived from these species was examined using restriction enzyme mapping and Southern blotting techniques. In the rRNA coding regions, restriction enzyme sites were conserved in Ae. aegypti and Ae. albopictus. In particular, sites that had been mapped in rDNA cloned from the Mauritius strain of Ae. albopictus mosquitoes were confirmed in cloned DNA from cultured Ae. alboptictus cells. The intergenic spacer region of the ribosomal DNA repeat unit in Ae. albopictus was longer than that in Ae. aegypti; contained multiple recognition sites for AluI, SstI, PvuI, and XhoI; and was more heterogeneous in DNA from cultured cells than in DNA from inbred laboratory mosquitoes. The rDNA copy number was 3- to 4-fold lower in cell lines from both Ae. albopictus and Ae. aegypti than in the corresponding adult mosquitoes. PMID- 1941932 TI - Occurrence and evolutionary significance of a California encephalitis-like virus in Aedes squamiger (Diptera: Culicidae). AB - More than 12,000 Aedes increpitus Dyar and 4,600 Aedes squamiger (Coquillett) were tested for the presence of arboviruses to test the hypothesis that there is a coevolutionary relationship between Aedes (Ochlerotatus) mosquitoes and California serogroup viruses. Five strains of a California encephalitis-like virus were isolated from adults reared from larvae of Ae. squamiger collected in January 1989 from a coastal salt marsh at Morro Bay, San Luis Obispo County, California. Viruses were isolated in Vero cell cultures and serotyped by cross neutralization tests. These isolates represent the first arboviruses isolated from this species. On the basis of morphology, Aedes squamiger has been included in the Aedes stimulans group of the subgenus Ochlerotatus. Other species within the Ae. stimulans group are vectors of California (CAL) serogroup viruses elsewhere in North America. Analysis of isozyme variability supports the inclusion of Ae. squamiger in the Ae. stimulans group and suggests that coastal populations of Ae. increpitus are the closest California relatives of Ae. squamiger. Recovery of virus from Ae. squamiger reinforces the relationship between CAL serogroup viruses and Aedes (Ocherlotatus) mosquitoes. However, the failure to isolate virus from large samples of Ae. increpitus from coastal and low elevation inland habitats suggests a complex evolutionary history involving both vertical and horizontal transmission mechanisms. PMID- 1941933 TI - Etiologic agent of Lyme disease, Borrelia burgdorferi, detected in ticks (Acari: Ixodidae) collected at a focus in Alabama. AB - The study was conducted at sites of known transmission of Borrelia burgdorferi in east central Alabama. The objectives were to determine species of ticks present at these sites, their host associations, and species of ticks and small mammals naturally infected with B. burgdorferi. A total of 451 hosts were examined for ticks, including cotton mice, Peromyscus gossypinus (Le Conte); cotton rats, Sigmodon hispidus Say & Ord; southern short-tailed shrews, Blarina carolinensis (Bachman); house mice, Mus musculus L.; golden mice, Ochrotomys nuttalli (Harlan); and white-tailed deer, Odocoileus virginianus (Zimmermann). Ticks were examined for B. burgdorferi using indirect and direct fluorescent antibody assays. Ear biopsy samples from rodents were cultured in modified Kelly's medium in attempts to isolate B. burgdorferi. A total of 859 Amblyomma americanum L., Dermacentor albipictus (Packard), D. variabilis (Say), Ixodes scapularis Say, and Rhipicephalus sanguineus (Latreille) were recovered from hosts and by dragging. A. americanum and I. scapularis accounted for 53.4% of all ticks collected. Nearly half of all ticks collected were examined for the agent. Spirochetes were detected in four nymphal and two adult A. americanum recovered from white-tailed deer and three larval I. scapularis recovered from cotton mice. No spirochetes were cultured from field-caught rodents. PMID- 1941934 TI - Arthropod faunal composition on Kentucky equine premises. AB - Thirty-nine arthropod species representing the families Muscidae, Chloropidae, Tabanidae, Simuliidae, Culicidae, and Ixodidae were collected from Kentucky equine premises using dry ice-baited canopy traps, light traps, water samples, tick drags, and animal inspections during late April to mid-October 1987 and 1988. Thirty-three species were collected from canopy traps, consisting of 74.3% muscid, 16.7% chloropid, 5.0% simuliid, 3.8% tabanid, and 0.2% culicid species. Light traps attracted eight culicid and water samples yielded three culicid species. One ixodid species was collected with drags, and animal inspections yielded two muscid and two ixodid species. Comparison of species assemblages among farms and across years using multivariate principal component analysis (PCA) yielded three distinct principal components, and PCA scores for each farm per year were correlated with biotic and abiotic environmental factors and management practices. The proximity to cattle herds was the best predictor of similarity in species assemblages among farms, reflecting the high percentage of muscid species collected. Poor management practices were partially responsible for proportionally larger populations of culicids, ixodids, and muscids on some farms. PMID- 1941935 TI - Survival and dispersal of horse flies (Diptera: Tabanidae) feeding on cattle sprayed with a sublethal dose of fenvalerate. AB - A mark-recapture study was undertaken to determine the fate of tabanids feeding on cattle sprayed with a sublethal dose of fenvalerate. A total of 15,465 tabanids belonging to at least 17 species and five genera were marked individually; flies were divided equally between control and fenvalerate-sprayed bullocks. Data were summarized for the four most abundant species: Tabanus fuscicostatus Hine, T. lineola F., T. pallidescens Philip, and T. wilsoni Pechuman. The recapture rate of tabanids was 6.6% for the control and 3.4% for the fenvalerate treatment. When the proportion of flies predicted to die or be unaffected after feeding on the sprayed bullocks was considered, an estimated 75% of the flies exposed to a sublethal knockdown dose survived and attempted to seek a subsequent host. Dispersal of tabanids was not affected by treatment. The recapture data after the first day of marking was significantly delayed for tabanids that fed on fenvalerate-sprayed bullocks. PMID- 1941936 TI - Borrelia burgdorferi in ticks (Acari: Ixodidae) from coastal Virginia. AB - Ixodid ticks removed from hosts and from vegetation during March-November 1987 at sites in coastal Virginia and North Carolina were examined for Borrelia burgdorferi. B. burgdorferi was evident in nine (22%) Ixodes cookei Packard removed from rice rats (Oryzomys palustris), a white-footed mouse (Peromyscus leucopus), and raccoons (Procyon lotor); four (6%) Amblyomma americanum (L.) removed from raccoons; and two (3%) Dermacentor variabilis (Say) removed from a raccoon and a rice rat. B. burgdorferi was also detected in Ixodes dentatus Marx removed from a brown thrasher (Toxostoma rufum), a Carolina wren (Thryothoros ludovicianus), and a towhee (Piplio erythrophthalamus); and in Haemaphysalis leporispalustris (Packard) removed from a brown thrasher and a white-throated sparrow (Zonotrichia albicollis) netted at Kiptopeke Beach, Va. Two Ixodes dammini Spielman, Clifford, Piesman & Corwin were collected on Parramore Island; one specimen was examined for spirochetes, and it was infected with B. burgdorferi. No spirochetes were detected in host-seeking A. americanum and Amblyomma maculatum Koch removed from vegetation. The plasma of one P. leucopus and sera obtained from two P. lotor contained antibodies to B. burgdorferi. All infected ticks and the seroreactive hosts were collected from the Eastern Shore of Virginia. PMID- 1941937 TI - Culicoides obsoletus (Diptera: Ceratopogonidae) as a causal agent of Culicoides hypersensitivity (sweet itch) in British Columbia. AB - Six horses severely affected by a seasonal dermatitis similar in both histopathology and epidemiology to Culicoides hypersensitivity (CH) and six unaffected or normal horses were inoculated intradermally with an extract of Culicoides obsoletus (Meigen), the most common Culicoides in southwestern British Columbia. Affected horses developed large welts within 20 min after injection, representing an immediate (type I) reaction; welts were largest 24 h or more after challenge, indicating in addition a delayed (type IV) reaction. This reaction was discernible for greater than 3 wk in some of the affected horses. Normal horses developed small welts which peaked 2-4 h after challenge. Affected horses were irritated by the injections and developed characteristically ridged skin at the injection sites, similar to that seen in natural lesions, whereas the normal horses showed neither discomfort nor clinical signs. C. obsoletus is one of the most numerous Culicoides species biting horses, feeds on parts of the body where lesions are found, and is, we believe, responsible for dermatitis in the Pacific Northwest. The skin test was repeated 2 yr later in three of the affected horses. In two, the reactions were similar to those in the first test, but in the third horse, the reaction was greatly reduced after the second test. This paralleled a decrease in the severity of its natural clinical signs. Thus, a skin test may be useful in the diagnosis of Culicoides hypersensitivity. PMID- 1941938 TI - A new species and an annotated world list of the sucking louse genus Neohaematopinus (Anoplura: Polyplacidae). AB - A new species of sucking louse, Neohaematopinus sundasciuri, collected from the tree squirrel, Sundasciurus juvencus, is described from Palawan Island, Philippines. An updated world list of the genus Neohaematopinus is presented; this documents descriptive citations, known hosts, and geographical distributions with interpretive annotations for each of the 32 species now included in the genus. The geographical distributions of Neohaematopinus sciuri and N. sciurinus are discussed. PMID- 1941939 TI - Effect of ivermectin on the ovarian development of Aedes aegypti (Diptera: Culicidae). AB - The effect of ivermectin (0.1 microgram/ml) on blood digestion, ovarian development, and ovipositional attributes of Aedes aegypti was studied using standard morphological and histological techniques. Uncoordinated movements and paralysis were observed in most ivermectin-treated females within 1 h after ingestion of blood containing the chemical. Eight days after the blood meal, 23.5% of the treated females had died, whereas no mortality occurred in controls. Formation of the peritrophic membrane and digestion of the blood meal were delayed in the surviving treated mosquitoes. The most striking effect of ivermectin on Ae. aegypti at this dosage was on ovarian development. Changes observed among ivermectin-treated mosquitoes included: blood digestion without development of ovarian follicles; degeneration of primary follicles and formation of ovarian dilatations within 24 h after ingestion of the chemical; significant reduction in the rate of vitellogenesis and follicle development; decreased egg production; reduced egg hatching; abnormal egg size and shape; and increased percentages of unhatched embryonated and sterile eggs. Although the precise action of ivermectin on Ae. aegypti is unknown, our studies indicate that the chemical directly or indirectly affects at least three major organ systems (nervous, digestive, and reproductive). PMID- 1941941 TI - Localization of leucomyosuppressin-like peptides in the central nervous system of the stable fly with immunocytochemistry. AB - An antiserum raised against leucomyosuppressin (LMS), the first insect neuropeptide shown to inhibit contraction of both visceral and skeletal muscles of insects, revealed the presence of LMS-like material in neurons of the adult stable fly, Stomoxys calcitrans (L.). Cells and their processes immunoreactive to the LMS antiserum were found in the brain, subesophageal, and thoracico-abdominal ganglia, with the majority of these neurons in the thoracico-abdominal ganglion. Positive immunostaining after preabsorption of the antibodies with the molluscan tetrapeptide FMRFamide, which absorbs the antibodies directed against the C terminal FLRFamide of LMS, indicates that structural similarities between LMS and the stable fly neuropeptide(s) extend beyond a similar C-terminal tetrapeptide sequence. PMID- 1941940 TI - Efficacy of a permethrin-based acaricide to reduce the abundance of Ixodes dammini (Acari: Ixodidae). AB - Permethrin-impregnated cotton was distributed to reduce abundance of immature Ixodes dammini Spielman, Clifford, Piesman & Corwin feeding upon white-footed mice (Peromyscus leucopus) and questing on vegetation at a private resort site (The Crane Reservation of The Trustees of Reservations in Ipswich, Mass.) located in coastal New England. This test constituted the first independent evaluation of the efficacy of this commercial product (Damminix). Over a 3-yr period, 2,000 applicator tubes containing treated cotton were distributed over the 7.3-ha site in 5 regularly scheduled applications. Mice removed treated fiber from the tubes and transported it to their nests. Within 3 wk of the first application, virtually all mice in the treated site were rendered free of ectoparasites. After the first season of application, no nymphal host-seeking I. dammini could be found on vegetation. Visitor and employee complaints about deer tick bites or ticks found on skin and clothing had been attributed to the site before treatment, but not thereafter. We confirmed the efficacy of Damminix for reduction of the abundance of vector ticks and thereby contributed to the protection of humans against Lyme disease at this site. PMID- 1941942 TI - Lyme disease in California: interrelationship of ixodid ticks (Acari), rodents, and Borrelia burgdorferi. AB - The association of immature ixodid ticks, several species of rodents, and the Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, was studied in two habitats in northern California in spring and summer 1985 and year-round in 1986. A total of 428 rodents were collected from ecotonal chaparral and a woodland-grass-rock outcrop; the former habitat yielded six species, the latter three species. The deer mouse, Peromyscus maniculatus (Wagner), and the pinon mouse, P. truei (Shufeldt), were the dominant species year-round and collectively comprised 78% of rodents captured within chaparral and 87% from the rock outcrop in 1986. In both habitats, rodents were trapped most frequently in winter and spring, and least often in summer and fall. A total of 306 rodent blood films from all six species were assayed for spirochetes by direct immunofluorescence; of these, only one film prepared from P. truei (n = 123 films from 53 individual mice) was found to contain spirochetes. Immature western black-legged ticks, Ixodes pacificus Cooley & Kohls, and Pacific Coast ticks, Dermacentor occidentalis Marx, were collected from each species of rodent. Larvae of I. pacificus infested P. maniculatus and P. truei in low numbers year round, but nymphs of this tick rarely parasitized these rodents. D. occidentalis larvae infested P. maniculatus and P. truei in spring and particularly in summer; nymphal ticks infested these mice primarily in summer. The efficiency of visual inspection for collecting immatures of these ticks from P. maniculatus ranged from 45 to 69% in spring and summer, whereas the efficiency of a drop-off technique appeared to be 100%. Spirochetes were detected in <1% of D. occidentalis larvae (n = 310) and nymphs (n = 120), and in approximately 4% of I. pacificus larvae (n = 75) derived from these hosts. The potential significance od these findings in the enzootiology of B. burgdorferi is discussed. PMID- 1941943 TI - Horizontal movement of adult Ixodes dammini (Acari: Ixodidae) attracted to CO2 baited traps. AB - The ability of male and female deer ticks, Ixodes dammini Spielman, Clifford, Piesman, & Corwin, to move horizontally was evaluated by performing a mark recapture study. In each of two experiments, 120 ticks were marked with fluorescent powder and released at predetermined distances from a CO2-baited trap. The mean recruitment distance was 1.8 m after 6 d of trap operation. This distance is appreciably lower than those calculated from previous studies of several other species of ixodid ticks, including Amblyomma americanum (9.9 m for 48 h) and Dermacentor andersoni (6.3 m for 48 h). Both the number of ticks attracted and the distance traveled to the trap were dependent upon the duration of trap operation (P less than 0.001 for both cases). PMID- 1941944 TI - Landing pattern of stable flies (Diptera: Muscidae) on the alsynite cylinder trap: effect of wind speed and direction. AB - The distribution of stable flies, Stomoxys calcitrans (L.), caught on adhesive coated Alsynite cylinder traps indicated that a significantly higher proportion of flies landed on the side most protected from the wind, and that flies were distributed equally on both sides of the traps bisected by the direction of the prevailing wind, and that the proportion of trapped flies decreased significantly with height on the trap. The landing pattern of house flies, Musca domestica L., appeared to differ from that of stable flies. As wind speed increased, the proportion of stable flies landing on the lower and downwind parts of the trap increased. PMID- 1941945 TI - Carrion insects of the Egyptian western desert. AB - A general survey was made on the zoosaprophagous insects and their associates in a natural ecosystem in the Egyptian western desert (80 km west of Alexandria, 12 km from the Mediterranean Sea shore). Two types of traps were used, one for flying insects and the other for soil-burrowing insects. Two types of decaying media were used as baits: the common freshwater fish (Tilapia zilii Gerv.) and the desert snail (Eremina desertorum). More than 30 insect species were trapped. The following orders and families were represented: Diptera (Calliphoridae, Sarcophagidae, Muscidae); Coleoptera (Histeridae, Scarabaeidae, Dermestidae, Tenebrionidae); Hymenoptera (Chalcididae, Pteromalidae, Eulophidae, Formicidae). Monthly totals of numbers trapped in each of these groups are presented. PMID- 1941946 TI - Circadian rhythm of egg hatching in Triatoma infestans (Hemiptera: Reduviidae). AB - The timing of hatching of Triatoma infestans (Klug) eggs was analyzed by means of time-lapse photography. Under a photoperiod of 12:12 (L:D) and constant darkness, maximum eclosion occurred at the end of the subjective night. Under constant light, the rhythmicity disappeared. Hatching rhythm seems to be maintained by a circadian endogenous oscillator. By hatching close to dawn, when relative humidity is high, insects may avoid excessive water loss. PMID- 1941947 TI - Detection of epizootic hemorrhagic disease virus in Culicoides variipennis (Diptera: Ceratopogonidae). AB - Nucleic acid hybridization was used to detect epizootic hemorrhagic disease (EHD) virus serotype 1 and serotype 2 in Culicoides variipennis (Coquillett). Adult females were inoculated intrathoracically with virus, then were assayed daily for the presence of viral RNA for 2 wk, at which time maximum virus replication is likely to occur. Viral RNA of EHD serotypes 1 and 2 was first detected by hybridization on days 9 and 7 after infection, respectively, and then for up to 14 days after infection. EHD serotype 1 viral RNA was detected by hybridization in infected flies fixed in ethanol at room temperature for 7 d and in unfixed (frozen) infected flies. However, weak false positives diminished prospects for application of this method. PMID- 1941948 TI - Collections of adult Ixodes dammini in Indiana, 1987-1990, and the isolation of Borrelia burgdorferi. AB - The collection records for Ixodes dammini Spielman, Clifford, Piesman & Corwin in Indiana are summarized for the period 1987-1990. In 1990, 13 of 729 deer examined were found to harbor adult I. dammini ticks. Eleven of these ticks were collected from 10 deer at a site in Newton County in northwestern Indiana. Borrelia burgdorferi spirochetes were isolated from a single female I. dammini tick collected from this site. PMID- 1941949 TI - Apparent incompetence of Dermacentor variabilis (Acari: Ixodidae) and fleas (Insecta: Siphonaptera) as vectors of Borrelia burgdorferi in an Ixodes dammini endemic area of Ontario, Canada. AB - From April to October 1990, white-footed mice, Peromyscus leucopus (Rafinesque), were examined for ectoparasites on Long Point, Ontario, the only endemic area for Ixodes dammini Clifford, Spielman, Piesman & Corwin and Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner known in Canada. Larval and nymphal I. dammini and Dermacentor variabilis (Packard), and adult fleas Orchopeas leucopus (Baker), Epitedia wenmanni (Rothschild), and Ctenophthalamus pseudagrytes Baker were common on trapped mice. Questing ticks were collected by dragging, near the sites of mouse trapping, from April to November 1990. Indirect immunofluorescent assay established that 58.3% of adult, 17.3% of nymphal, and 0.15% of larval I. dammini questing at Long Point were infected with B. burgdorferi, indicating that infected mammalian reservoir hosts are common. None of 593 adult, 2 nymphal, and 4 larval D. variabilis collected while questing were infected; and only 1 of 322 fleas (O. leucopus) removed from white-footed mice was infected. The fact that no unfed adult D. variabilis and only one flea were infected, in a situation where the probability of exposure of hematophagous ectoparasites is moderately high, suggests that this species of tick and the fleas examined are poor vectors for the Lyme disease spirochete. PMID- 1941950 TI - Should patients be allowed to look after their own medical records? PMID- 1941951 TI - Paying for health. AB - Health care systems, irrespective of how they are financed, present the paradox that to some observers they appear as a major component of social benefits, while to other observers they seem both excessively costly and limited in their effectiveness. These differing perceptions may be explained in part by the diversity of the determinants of health and disease, only some of which are amenable to those preventive or therapeutic measures encompassed in a health care system--the majority of determinants being genetic, societal, or else uninfluenced by those interventions at present available within a health service. The share of national resources which should be devoted to health care, and the method of raising resources, are primarily matters for political decision; but a national system has advantages both of economy and of comprehensiveness. But when it comes to allocation of resources within the established health budget, the knowledge and skills of health professionals are essential to informed decision making. The possibilities depend critically on the 'state of the art' at a given time, as is illustrated by the radical changes over time in what could be done for patients with renal failure; and health professionals are likely to be most aware of current options, and of how to choose between them. More speculatively, they are also less likely to confuse the attitudes appropriate to providing a service with those required to run a business. PMID- 1941952 TI - Autonomy, religious values, and refusal of lifesaving medical treatment. AB - The principal question of this paper is: Why are religious values special in refusal of lifesaving medical treatment? This question is approached through a critical examination of a common kind of refusal of treatment case, one involving a rational adult. The central value cited in defence of honouring such a patient's refusal is autonomy. Once autonomy is isolated from other justificatory factors, however, possible cases can be imagined which cast doubt on the great valuational weight assigned it by strong anti-paternalists. This weight is sufficient, in their estimation, to justify honouring the patient's refusal. There is thus a tension between the strong anti-paternalist's commitment to the sufficiency of autonomy and our intuitions respecting such cases. Attempts can be made to relieve this tension, such as arguing that patients aren't really rational in the circumstances envisaged, or that other values, such as privacy or bodily integrity, if added to autonomy, are sufficient to justify an anti paternalistic stance. All such attempts fail, however. But what does not fail is the addition of religious freedom, freedom respecting a patient's religious beliefs and values. Why religious freedom reduces the tension is then explained, and the specialness of religious beliefs and values examined. PMID- 1941953 TI - To treat or not to treat: the legal, ethical and therapeutic implications of treatment refusal. AB - Health professionals faced with refusal of life-saving treatment may wish to override a person's wishes, especially if that person suffers from a mental disorder. Mental illness does not automatically mean a patient is incapable of making decisions of this nature. It is not always clear whether an individual is legally competent to decide whether to undergo treatment or not. This article discusses a clinical example and analyses some of the moral implications. PMID- 1941954 TI - How I was almost aborted: reflections on a prenatal brush with death. AB - After recently meeting with his biological parents, the author--a 29-year-old married male--learned he had been an hour away from being aborted, being 'saved' only by extraordinary circumstances. In the paper the author reflects upon previous strong pro-choice beliefs and reasserts his commitment to a pro-choice philosophy, integrating his new personal experience. The paper pays particular attention to the biological mother's experience and how her fresh insights have reinforced the author's views on abortion. PMID- 1941955 TI - Medical records: practicalities and principles of patient possession. AB - This review of issues and research is in two parts: 1) practical problems surrounding patient-held records and 2) ethical arguments for and against patient held records. We argue that research on patient-held records indicates that there are no substantial practical drawbacks and considerable ethical benefits to be derived from giving patients custody of their medical records. PMID- 1941956 TI - Enforced death: enforced life. AB - The notion of 'quality of life' frequently features in discussions about how it is appropriate to treat folk at the beginning and at the end of life. It is argued that there is a disjunction between its use in these two areas (1). In the case of disabled babies at the very beginning of life, 'quality of life' considerations are frequently used to justify enforced death on the basis that the babies in question would be better off dead. At times, babies with severe disabilities are thus allowed to die or even killed. In the case of terminally ill people 'quality of life' is also important in guiding the actions of doctors. However, in the case of individuals who do not wish to live any longer because their quality of life is so poor that they would rather be dead, quality of life is likely to be dropped as a guiding principle. Thus patients who wish to die and ask to be killed, will most often be forced to endure enforced life. PMID- 1941957 TI - The diffusion of medical technology: free enterprise and regulatory models in the USA. AB - The diffusion of technology in the US has taken place in an environment of both regulation and free enterprise. Each has been subject to manipulation by doctors and medical administrators that has fostered unprecedented ethical dilemmas and legal challenges. Understanding these developments and historical precedents may allow a more rational diffusion policy for medical technology in the future. PMID- 1941958 TI - Involving patients in do not resuscitate (DNR) decisions: an old issue raising its ugly head. AB - A recent paper in this journal (1) suggests that involving terminally ill patients in choices concerned with Cardio-Pulmonary Resuscitation (CPR) produces 'psychological pain' and therefore is ill-advised. Such a claim rests on anecdotal observations made by the authors. In this paper I suggest that drawing conclusions in ethics, no less than in science, requires a rigorous framework and cannot be relegated to personal observation of a few cases. The paper concludes by suggesting that patients, if we acknowledge their valid interest in making their own choices, must themselves be allowed to make a prior choice about choosing. Those who may not wish to choose may properly be relieved of this burden and may allow another to choose for them. Routinely allowing others to make choices for competent adults, however, is likely to decrease communication with the dying patient and to introduce an atmosphere of suspicion and fear and to exclude the competent patient from his/her rightful place in the community. PMID- 1941959 TI - Ethics of using Nazi research. PMID- 1941960 TI - Ethics of preventive medicine. PMID- 1941961 TI - Donors and sellers of organs. PMID- 1941962 TI - Genetic counselling in facioscapulohumeral muscular dystrophy. AB - Clinical data are presented from a survey of 41 families with dominantly inherited facioscapulohumeral muscular dystrophy (FSHD) in which over 500 family members were examined, including 168 affected subjects. New mutation could account for six isolated cases. Results suggest that 33% of heterozygotes over 40 years are mildly affected and a majority develop significant lower limb weakness; 19% over 40 years require wheelchairs. Presymptomatic testing of serum creatine kinase level (CK) is limited as a raised level occurs in only 80% of affected males under 40 years and 48% of affected women. Distribution of weakness, severity, age at onset, and CK varied between subjects, but provided no clinical evidence for genetic heterogeneity in a comparison between the 11 largest families. The conclusion of genetic homogeneity in FSHD, including subjects previously diagnosed as FSH type spinal muscular atrophy, is strongly supported by recent genetic linkage data. PMID- 1941963 TI - A closely linked DNA marker for facioscapulohumeral disease on chromosome 4q. AB - Close linkage of a hypervariable DNA probe on chromosome 4q (pH30, locus D4S139) has been found with the locus for facioscapulohumeral disease. Three recombinants were identified in a total of 140 meioses, giving a maximum lod score of 36.77 at a recombination fraction of 0.02. All but two of the families studied proved informative with this probe; all informative families showed evidence of linkage (except one family with a single scorable meiosis), making genetic heterogeneity unlikely from our data. The close linkage and highly informative nature of the probe will make it suitable for clinical application in presymptomatic and prenatal diagnosis. We have also confirmed loose linkage with the marker (Mfd22, locus D4S171) used to establish the initial assignment of the disorder to chromosome 4. PMID- 1941964 TI - A male with type I orofaciodigital syndrome. AB - We describe a three generation family with three females showing minor features of orofaciodigital syndrome type I and a severely affected male in the third generation. In addition to the classical features of OFD I, the male had bilateral duplication of the halluces, a feature diagnostic of OFD II, and an atrioventricular septal defect. Heart defects have not previously been reported in OFD I but have been reported in OFD II. It is important to examine the mothers of all male neonates with orofaciodigital syndrome with care before making a diagnosis of OFD II. PMID- 1941965 TI - Miller syndrome (postaxial acrofacial dysostosis): further evidence for autosomal recessive inheritance and expansion of the phenotype. AB - A sibship with postaxial acrofacial dysostosis syndrome (Miller syndrome) is reported. In addition to the characteristic facial and limb defects, previously undescribed anomalies, including midgut malrotation, gastric volvulus, and renal anomalies, are recorded. PMID- 1941966 TI - A new form of autosomal dominant arthrogryposis. AB - We report a man and his son with congenital limb contractures, limitation of ocular movements, and an electroretinal abnormality. They appear to have an autosomal dominant form of arthrogryposis, distinguishable from other previously classified forms of this disorder. PMID- 1941967 TI - Cerebrocostomandibular syndrome in four sibs, two pairs of twins. AB - We report four sibs, two pairs of twins, with cerebrocostomandibular syndrome (CCMS). The family history was negative. All four babies had the characteristic features of CCMS, including Pierre-Robin anomalad and rib dysplasia. Cerebral involvement was evident in two of the patients who had suffered perinatal asphyxia. The presence of the syndrome in all four sibs together with the negative family history in previous generations is consistent with Mendelian autosomal recessive inheritance with high penetrance. PMID- 1941968 TI - Encephalopathy with intracerebral calcification, white matter lesions, growth hormone deficiency, microcephaly, and retinal degeneration: two sibs confirming a probably distinct entity. AB - Two sibs with an encephalopathy, including intracerebral calcification and white matter lesions, dwarfism owing to growth hormone deficiency, and retinal degeneration are reported. The onset of the disease in both patients occurred with retardation of motor development during the first year of life. Later, dwarfism, mental retardation, spasticity, ataxia, and retinal degeneration became apparent. These cases probably represent some form of connatal leucodystrophy. The differential diagnosis is discussed. PMID- 1941969 TI - Disorganisation: a possible cause of apparent conjoint twinning. AB - A patient with duplications of the internal organs and external structures of the lower half of the body might have traditionally been explained by incomplete twinning. The presence of a fifth digit-like structure protruding from the lower abdomen and facial and cranial abnormalities suggested that, instead, he might be an example of the disorganisation mutant. However, the presence of cardiac defects was not readily explained by invoking the presence of this mutation. PMID- 1941970 TI - An animal model for maternal phenylketonuria. PMID- 1941971 TI - The non-deletion type of alpha thalassaemia/mental retardation: a recognisable dysmorphic syndrome with X linked inheritance. PMID- 1941972 TI - Further evidence for the location of the BPES gene at 3q2. PMID- 1941973 TI - Cholera: an ancient disease in modern times. PMID- 1941974 TI - [Retroperitoneal duodenal rupture during closed abdominal trauma]. AB - Duodenal retroperitoneal wound after blunt abdominal trauma, is a well known, and a classical entity. Most of the patients are operated with delay and this lesion could easily be missed at laparotomy if not searched for. Mortality and morbidity are much higher if the diagnosis is delayed more than 24 hours. These lesions should be strongly suspected after any blunt abdominal trauma, and repeated clinical assessment is mandatory in the conscious patient. Gastrografine upper GI study and CT Scan are interesting diagnosis procedures when the patient is unconscious or should be anesthesized. At laparotomy, the presence of a central retroperitoneal hematoma should guide the surgeon to explore the duodenum. Treatment depend on the time of diagnosis, the severity of the wound, and the associated pancreatic lesions. PMID- 1941975 TI - Cancer of the pancreas experience at the American University of Beirut. AB - Cases of cancer of the pancreas seen at the American University Medical Center over a 9 year period are reviewed. Newer methods of diagnosis are emphasized as well as the dismal outlook in the outcome of the patients. PMID- 1941976 TI - [Splenic conservation in gunshot wounds]. AB - The spleen is a frequently injured organ in abdominal trauma. Because of complications, specially post-splenectomy sepsis, conservative treatment is recommended whenever possible, either by adequate medical treatment or by conservative surgery. 65 consecutive cases of proven splenic injuries by bullets or shrapnells were admitted at St George's Hospital between 1978 and 1987. Splenectomy was done in 55 patients with almost always abdominal or thoracic associated lesions. 7 patients had a conservative surgical treatment (suture 3 cases, suture with epiploplasty 2 cases, suture with Gelfoam 1 case, partial resection with epiploplasty 1 case). 3 cases had a conservative medical treatment. Clinical, biological and radiological criterias for a medical or conservative surgical management, are defined. PMID- 1941977 TI - Issues in psychiatric research and diagnosis. AB - Diagnosis in psychiatry, as in other fields of medicine is a very important step in the development of research. This article reviews its importance and its progress in the field of psychiatry. Important yardstics are: Feighner Criteria, Research Diagnostic Criteria, DSMIII-R and IDC-X. PMID- 1941978 TI - [After a myocardial infarction]. AB - According to the literature and our experience, une expose our conception and our methodology of taking in charge patients after acute myocardial infarction. It is important to evaluate risks based on clinical data and exercise tests. Cardiac rehabilitation is taught of as a number of measures acting on the physical, the psychiatric and the socio-occupational levels, the importance of correcting risk factors and long-term follow-up. PMID- 1941979 TI - [Substernal goiters]. AB - In a series of 363 patients operated for goiter, 60 were retrosternal (16.5%). The female incidence although less than in cervical goiters remains predominant (2,5:1). Most patients are in older age group, 68% being above 40 years. The majority of goiters are multinodular and of long duration. Bilateral (37%) and left sided location (43%) were common. The incidence of cancer was 7%, thyrotoxicosis was noted in 5 patients (8%). Most patients were symptomatic (97%). Diagnosis is easily done by physical examination, chest X-Ray and thyroid scintigraphy. Computed tomography might be helpful. Retrosternal goiter is an indication to surgery except in high risk patients. The cervical approach has been used in 98% of cases. There were no post-operative death and no major complications (compressive hematoma, laryngeal nerve paralysis, hypocalcemia). PMID- 1941981 TI - [History of castration in Lebanon ...and other places]. PMID- 1941980 TI - Experience on fracture dislocation of the humeral head. A report of two cases. AB - Two cases of anterior-inferior fracture dislocations through the anatomical humeral neck combined with avulsion of the greater tuberosity are reviewed. The management, complications and results are analyzed. PMID- 1941982 TI - Failures in reconstructive mitral valve surgery. AB - From 1969 to 1985, mitral valve repairs using Carpentier's technique were performed for acquired mitral valve incompetence. 72 patients required a reoperation 3 days to 13 years later (mean 5 +/- 3.5 years). The reoperation rate risk was dependent upon the etiology: Barlow 0.6 +/- 0.2% patient year, fibro elastic deficiency 0.7 +/- 0.3, endocarditis 1.7% Rheumatic disease 4.6 +/- 1.4%. The risk of reoperation in Rheumatic disease is significantly higher (p less than 0.05) than in degenerative disease. The causes of failures could be categorized into two groups according to whether they are surgeon related or valve related: Group I, Prosthetic ring dehiscence or malposition 15%, anulus dilatation (when no ring was implanted) 4%, triangular resection of the anterior leaflet 4% residual prolapse 8.3%. Group II, Recurrent prolapse 16.6% valve stenosis 17%, leaflet retraction 35%. Failures in Group I can be reduced with "increased" experience as opposed to group II. At reoperation valve repair was possible in 15.3% of the cases whereas valve replacement was necessary in 84.7% with an overall operative mortality of 1.4%. We conclude that mitral valve repair in acquired mitral incompetence carries out a small risk of reoperation. Most of the repair failures are surgeon related in degenerative disease and valve related in rheumatic disease. PMID- 1941983 TI - A fuzzy approach to the rate control in an artificial cardiac pacemaker regulated by respiratory rate and temperature: a preliminary report. AB - Fuzzy theory was applied to the rate control of a cardiac pacemaker which uses two parameters, respiratory rate and temperature, as the parameters for rate regulation. Using 25 fuzzy reasoning rules derived from five mongrel dogs, the pacing rates in three animals were calculated and compared with the intrinsic heart rates. It is concluded that the fuzzy method is well suited for the rate determination of a multi-parameter rate-responsive cardiac pacemaker. PMID- 1941985 TI - Assessment of a commercial pH electrode used with blood. AB - With the recent development of ion selective electrodes, potentiometry has entered a new era of usefulness ranging from pollution control to the investigation of single cells. Routine use of these sensors in the clinical environment is severely restricted due to errors associated with the reference electrode. Due to the Nernstian response of the potentiometric sensors the entire reference and ion selective electrodes are housed within a thermostatically controlled heater assembly. A clinically based thermostatically controlled combined ion selective/reference electrode system is discussed and a simple algorithm is presented to correct for the additional liquid junction potential encountered when monitoring biological solutions. PMID- 1941984 TI - The effect of varying LED intensity on pulse oximeter accuracy. AB - Most pulse oximeters automatically alter the intensity of their light-emitting diodes (LEDs) according to the absorption of the finger, toe or earlobe to which they are attached. This paper investigates the effect of changing LED intensity on pulse oximeter accuracy. Our results show that the peak wavelength of a red LED typically increases by 8 nm as its intensity is increased ten-fold. To determine whether this shift introduces a significant error, a simple theoretical model based on the Beer-Lambert law is used. The model predicts that a 10:1 change in LED intensity results in a 2.5% error at 50% arterial oxygen saturation (SpO2). At high saturations (SpO2 greater than or equal to 85%) the model predicts little loss of accuracy and thus any effect due to changes in LED intensity will be apparent only at low saturations. PMID- 1941986 TI - Technology in interventional cardiology: percutaneous transluminal coronary angioplasty. AB - Percutaneous transluminal coronary angioplasty (PTCA) is now capable of providing myocardial revascularization in a majority of patients, but significant problems with the technique remain. It is unsuitable for dealing with diffuse coronary artery disease, chronically occluded vessels may be impossible to disobliterate, and disease of the distal coronary vessel may be difficult to reach with a balloon. Approximately 5 percent of all procedures may be complicated by acute occlusion of the target vessel, usually by dissection of the arterial intima, often resulting in a need for emergency coronary artery bypass surgery (CABG). Furthermore, there is recurrence of the dilated lesion--'restenosis'--in approximately 30 percent of cases in the first 3 to 6 months after PTCA. Advances in this technique, since its introduction in the mid 1970s, have been directed at making initial success more likely, obviating the need for emergency CABG, and reducing the incidence of restenosis. PMID- 1941987 TI - Evaluation of the Rosco system for the identification of Listeria species. AB - The Rosco system was used to identify previously confirmed isolates of the seven currently recognised species of Listeria. These included reference cultures and recent isolates from clinical material, food products and environmental sources. The system identified all correctly. Results were obtained after 4 h if heavy inocula, as suggested by the manufacturers, were used. The method may be used to aid identification of isolates of Listeria from clinical and non-clinical specimens and would be of particular value in laboratories examining small numbers of isolates relatively infrequently. Essential tests not included in the system are beta-haemolysis on sheep-blood agar and the CAMP test. PMID- 1941988 TI - Adherence of Helicobacter pylori to human gastric epithelial cells in vitro. AB - Gram-negative spiral organisms, currently referred to as Helicobacter pylori, are associated with primary gastritis and duodenal ulceration. The organisms colonise gastric mucus and adhere to epithelial cells of inflamed antra. To further examine the binding of H. pylori to human gastric epithelial cells, we developed and characterised an in-vitro bacterial adherence assay. Scanning electronmicroscopy suggested that spiral-shaped bacteria were adherent to the surface of KATO-III cells which were derived from a human gastric adenocarcinoma. Transmission electronmicroscopy confirmed the attachment of H. pylori to these epithelial cells in tissue culture. Some bacteria were adherent to intact microvilli, others were closely adherent to the plasma membrane in regions where microvilli were effaced. In studies with radiolabelled H. pylori, adherence to epithelial cells in tissue culture contrasted with minimal binding of bacteria to polystyrene wells alone. Incubation of bacteria with gastric cells at 4 degrees C significantly reduced adherence of H. pylori. We conclude that adherence of H. pylori to gastric epithelial cells in tissue culture involved "attachment and effacement mechanisms". This assay could serve as a suitable in-vitro model for the study of the bacterial adhesins and host receptors which mediate attachment of H. pylori to gastric epithelial cell surfaces. PMID- 1941989 TI - The production and activity in vivo of Proteus mirabilis IgA protease in infections of the urinary tract. AB - Immunoblotting of urine from 21 patients of both sexes and of wide age range who had a Proteus mirabilis urinary tract infection (UTI) showed that 14 (64%) specimens contained immunoglobulin A (IgA). In nine (64%) of these the IgA heavy chain had been degraded to fragments of a size identical to those formed when purified IgA was degraded by pure P. mirabilis protease. Urine from patients with clinical evidence of upper UTI contained fragmented IgA and in some of these urine samples P. mirabilis protease activity was detectable. Urine infected with a non-proteolytic strain contained only intact IgA. It is concluded that P. mirabilis IgA protease is produced and is active during infections of the urinary tract. PMID- 1941991 TI - Nucleotide sequence of dihydrofolate reductase type VI. AB - The complete sequence of the type VI dihydrofolate reductase (DHFR) gene from plasmid pUK672 was determined. The structural gene coded for a polypeptide of 157 amino acids which had a deduced mol. wt of 17,424. Comparison with amino-acid sequences of the type I, type V and Escherichia coli K12 chromosomal DHFRs showed that there was 63%, 61% and 31% homology respectively. Putative RNA polymerase and ribosomal binding sites were identified proximal to the initiation codon and a feature consistent with transcription termination was present distal to the coding region. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed that the enzyme had a subunit mol. wt of 17,500. PMID- 1941990 TI - Susceptibility to beta-lactam antibiotics of mutant strains of Xanthomonas maltophilia with high- and low-level constitutive expression of L1 and L2 beta lactamases. AB - Xanthomonas maltophilia produces two inducible beta-lactamases, L1 and L2, and resists the antimicrobial activity of beta-lactam antibiotics, including carbapenems. L1 is a zinc-metaloenzyme with carbapenemase activity; L2 is an unusual cephalosporinase. Mutant strains with high- and low-level constitutive expression of these enzymes were derived from three reference strains of X. maltophilia. With a single exception, the mutant strains had altered expression of both enzymes, indicating that these beta-lactamases share regulatory components. The exception was a mutant strain that had low-level constitutive (basal) expression of L1 enzyme but remained inducible for L2. A parent strain with low-level beta-lactamase inducibility was more susceptible to penicillins, cephalosporins and carbapenems than were those in which higher levels of enzyme activity were inducible. Mutations that caused high-level constitutive beta lactamase expression increased resistance to penicillins and newer cephalosporins. beta-Lactamase basal mutant strains, including the one that remained inducible for L2 enzyme, were more susceptible than inducible strains to these drugs. Organisms with inducible or high-level constitutive beta-lactamase expression were equally resistant to meropenem and imipenem but basal mutant strains, including the one that remained inducible for L2 enzyme, were more susceptible to meropenem than imipenem. Minimal inhibitory concentrations of meropenem, penicillins and cephalosporins, but not imipenem, were greater on Mueller Hinton agar than on IsoSensitest or Diagnostic Sensitivity Test agars. This behaviour was independent of beta-lactamase inducibility, and may reflect permeability differences between cells grown on different media. PMID- 1941992 TI - An Indian hospital study of viral causes of acute respiratory infection in children. AB - From Sept. 1986 to Jan. 1989, a hospital-based study was conducted on 736 children, under 5 years of age, with acute respiratory infection. Nasopharyngeal secretions were examined for viruses by culture and by immunofluorescence. Viruses were detected in 22% of specimens: respiratory syncytial (5%), parainfluenza (5%), influenza A (4%), influenza B (2%), adenovirus (3%), measles (3%). The highest rates of detection were with patients diagnosed clinically as pneumonia or upper respiratory tract infection. The case fatality rate was very high (43%) in children with measles virus infection. PMID- 1941994 TI - The assessment of faecal flora in patients with inflammatory bowel disease by a simplified bacteriological technique. AB - A semi-quantitative bacteriological method was used to study faecal flora in 42 patients with Crohn's disease, 37 with ulcerative colitis and 21 healthy controls. Faecal homogenates were plated on primary isolation plates by a technique that allowed the growth of various microbial isolates to be assessed on a visual 1(+)-5+ score. This method was first calibrated against a standard quantitative bacteriological technique, which confirmed the reliability and reproducibility of the results obtained by the simpler method. Patients with clinically active Crohn's disease (22) had significantly higher total aerobe scores than patients with quiescent disease (20) (p less than or equal to 0.006) or ulcerative colitis (p less than or equal to 0.04) or normal controls (p less than or equal to 0.02). The scores of Escherichia coli were parallel to those of total aerobes. Lactobacillus and bifidobacteria scores were significantly reduced in patients with Crohn's disease compared to those with ulcerative colitis and controls. The anaerobic flora in both Crohn's disease and ulcerative colitis was indistinguishable from that of controls. Bacteroides vulgatus and B. fragilis were the predominant bacteroides in all groups. Patients with ulcerative colitis, regardless of disease activity, harboured faecal flora that did not differ from that of normal controls. The abnormal faecal flora in Crohn's disease did not correlate with established clinical and laboratory indicators of disease activity. PMID- 1941993 TI - Comparison of immunofluorescence and culture for the detection of Actinomyces israelii in wearers of intra-uterine contraceptive devices. AB - A direct immunofluorescence (IF) method was compared with traditional culture methods for the detection of Actinomyces israelii in endocervical and intra uterine-device (IUD) smears from 124 IUD wearers. Of 11 specimens that gave positive results by IF, only one was positive by culture. Of the 10 patients with positive IF specimens, three (30%) had signs and symptoms suggestive of pelvic infection and no other pathogen was detected. Direct IF of cervical smears offers a simple, relatively cheap method to screen IUD wearers for A. israelii. Clinical management of such cases is discussed. PMID- 1941995 TI - Serological diagnosis with the Chlamydia Spot-IF test. AB - Using a set of sera for which full chlamydial micro-immunofluorescence results suggested a clear diagnosis, we have evaluated the Chlamydia Spot-IF test (bioMerieux), which allows a comparison of titres to Chlamydia trachomatis and C. psittaci antigens. A modification of the test in which the antigen slides were pre-treated with a monoclonal antibody to chlamydial lipopolysaccharide, improved its ability to differentiate infections with C. trachomatis from those with C. psittaci or C. pneumoniae. PMID- 1941996 TI - An assessment of the Kemble Star 700 sample processor for the automation of complement fixation and ELISA tests in a microbiology laboratory. AB - A Kemble Robotic sample processor was programmed to perform routine serological tests for microbiology. Accuracy of dispensed volumes was assessed and precision of dilutions was compared with manual methods. An appraisal of time taken to perform complement-fixation and enzyme-linked immunosorbent assays by manual and automated methods was undertaken. Labour requirements were reduced when processing large numbers of samples and the reproducibility of more demanding tests was improved by the greater accuracy of the robotic manipulations. PMID- 1941997 TI - Expression in vivo of additional plasmid-mediated proteins during intestinal infection with Yersinia enterocolitica serotype O8. AB - The decisive aspect of Yersinia enterocolitica virulence in vivo is the ability of the plasmid-bearing bacteria to resist the immune response within the host tissue. The expression of plasmid-mediated virulence proteins was investigated in the intestinal lumen and in the Peyer's patches of infected mice. Three novel plasmid-mediated outer-membrane proteins have been identified with antisera raised against bacteria grown in vivo. When the bacteria were grown in the intestinal lumen, all plasmid-coded proteins known to be expressed in vitro, except the 26-Kda protein were expressed. Additionally, a novel outer-membrane protein of 23 Kda was synthesised. After penetration into the Peyer's patches, two further proteins of 240 and 210 Kda were expressed. None of these three proteins was detected in the outer membrane of bacteria grown in vitro. By contrast, plasmid-coded released proteins, which are abundantly synthesised in Ca(2+)-deficient media in vitro, were not detectable in the ileal lumen nor in the tissue of infected Peyer's patches, which suggests that they are not required for Y. enterocolitica pathogenesis. PMID- 1941998 TI - Identification of enteropathogenic Escherichia coli isolated in Britain as enteroaggregative or as members of a subclass of attaching-and-effacing E. coli not hybridising with the EPEC adherence-factor probe. AB - Strains of Escherichia coli from sporadic cases of diarrhoea and belonging to serotypes O44:H18, O55:H7, O111ab:H21, O111ab:H25 or O126:H27 were examined for virulence properties. With the exception of O111ab:H25 these are considered to be classical enteropathogenic E. coli (EPEC) serotypes. The strains had been isolated in Britain from the faeces of children less than 3 years old. Of the serotypes examined, 7 of 13 O44:H18 strains, all of 10 O111ab:H21 strains and 13 of 21 O126:H27 strains belonged to the enteroaggregative class of E. coli (EAggEC) that attached to HEp-2 cells in the characteristic aggregative pattern and hybridised with the EAggEC probe. They also caused mannose-resistant haemagglutination of rat erythrocytes, a property which may be a useful marker for their identification. Strains of O44:H18 with similar properties were also isolated from three small outbreaks in Britain, one of which involved elderly patients. EAggEC have not been considered previously as aetiological agents of diarrhoea in developed countries and have rarely been reported as belonging to EPEC serotypes. All 15 O55:H7 strains and seven of eight O111ab:H25 strains were also considered to be potentially diarrhoeagenic as they gave localised attachment (LA) to HEp-2 cells that resulted in a positive fluorescence actin staining test. This test is considered to correlate with the attaching-and effacing virulence mechanisms of EPEC in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1941999 TI - Comparison of ultracentrifugation and polyethylene glycol precipitation for concentration of hepatitis B virus (HBV) DNA for molecular hybridisation tests and the relationship of HBV-DNA to HBe antigen and anti-HBe status. AB - A 32P-labelled DNA probe was used to examine 50 hepatitis B surface antigen (HBsAg)-positive sera for the presence of hepatitis B virus (HBV) DNA. HBV-DNA was detected in all 21 HBeAg-positive samples, in one out of 21 anti-HBe-positive samples and in three out of eight HBeAg- and anti-HBe-negative samples. The results of this DNA hybridisation test correlated well with HBeAg status and could be used to determine infectivity in HBeAg- and anti-HBe-negative samples. Ultracentrifugation was marginally superior to polyethylene glycol precipitation for concentrating HBV-DNA from serum. PMID- 1942000 TI - Bacteroides ureolyticus (NTU) medium for the selective recovery of Bacteroides gracilis. AB - Bacteroides gracilis is a gram-negative anaerobic bacillus which requires formate and fumarate for growth; it has been implicated in periodontal disease and serious infections of the head and neck. In this study, Bacteroides ureolyticus (NTU) medium was tested for its ability to allow the growth of B. gracilis and other formate-fumarate requiring gram-negative anaerobes and to enable the recovery of these organisms from clinical specimens. All reference strains grew on NTU medium with the exception of Wolinella recta and formate-fumarate requiring organisms were isolated from 18 of 20 samples of subgingival dental plaque from patients with chronic periodontitis. B. gracilis was the commonest species isolated (14 of the 29 isolates); B. ureolyticus was not found. PMID- 1942001 TI - Typing of Streptococcus pyogenes by pyrolysis mass spectrometry. AB - Strains of Streptococcus pyogenes from an outbreak in an oncology ward (13) and routine isolates from sporadic cases (6) were examined blind by pyrolysis mass spectrometry (Py-MS), extending previous work on epidemiological typing. This outbreak appeared more complex than one reported previously, but Py-MS and conventional typing results were in complete agreement. The results confirm the potential of Py-MS as a rapid method for identification at strain level in studies of cross infection. PMID- 1942002 TI - Nonhuman primate models for AIDS III. Proceedings of a meeting, October 1990. PMID- 1942003 TI - Recovery of the simian immunodeficiency virus (SIV) and depression of colony formation in in vitro infected progenitor cell-enriched rhesus bone marrow (BM). AB - Rhesus progenitor-enriched BM was exposed overnight to SIV and cultured in a limiting dilution assay where the potential for progenitor interaction with lymphocytes or macrophages was low. Virus was consistently isolated late in culture, detection being aided by coculture with CEM174 lymphoblasts. Although infected cells had reduced clonogenic activity, colonies were indistinguishable from those derived from uninfected BM with respect to proliferative potential, morphology, and longevity in culture. Primate immunodeficiency viruses, therefore, may infect immature BM populations, directly affecting hematopoietic activity. PMID- 1942004 TI - Infection of rhesus monkeys with topical instillation of simian immunodeficiency virus (SIV)B670 into the conjunctival sac. AB - We tested the ability of SIV to cause local and systemic infection in three rhesus monkeys after topical instillation of cell-free virus into the conjunctival cul-de-sac. Conjunctivitis or other signs of infection were monitored after inoculation. Conjunctiva were swabbed for virus culture and biopsied for PCR. Changes in lymphocyte subsets, seroconversion, antigenemia, and virus isolation from PBL were assessed systemically postinoculation. Viral DNA was detected in conjunctival biopsy by PCR in one of three animals that later developed systemic infection. The other two animals remained uninfected. These data demonstrate that the conjunctiva is a route by which SIV (and perhaps HIV) may cause systemic infection. PMID- 1942005 TI - Severe autoimmune hemolytic anemia in SIVsmm9-infected Macaca mulatta. AB - One of 15 rhesus macaques infected with SIVsmm9 developed profound hemolysis with spherocytosis, reticulocytosis, and IgG and complement at the red blood cell surface. A female offspring born to this animal developed similar findings. Furthermore, cold agglutinins were noted in samples from both animals. Four of the 13 animals remaining in the cohort had weakly positive antiglobulin tests but were not anemic. Autoimmune hemolytic anemia may be an underrecognized cause of anemia in SIV infection. PMID- 1942006 TI - Early SIV encephalopathy. AB - SIV encephalopathy was studied in rhesus macaques early after intracerebral (IC) or intravenous (IV) inoculation. Although SIV was detected in the brain of all IC inoculated animals, the CNS showed moderate neuropathological changes. IV inoculated animals presented a spectrum of brain changes ranging from perivascular infiltrates to multinucleated giant cells. CNS infection was detected as early as seven days post-IV-inoculation, mostly in a perivascular localization. Using combined immunohistochemistry and in situ hybridization, infected cells were shown to express macrophage markers. PMID- 1942007 TI - Antibody-dependent enhancement and neutralization pattern of sera from SIV infected or HIV-2-vaccinated rhesus monkeys. AB - Neutralizing and enhancing activities in sera were detected by using an in vitro infection assay of HUT78 cells. Ten animals were vaccinated with HIV-2ROD recombinant vaccinia viruses and respective purified proteins. Only sera from monkeys vaccinated with env elicited neutralizing antibodies. No antibody dependent enhancement (ADE) properties were detected in all the tested sera. Six other macaques were infected with SIV-mac251. All of them had detectable ADE properties in their sera. No major neutralizing activity was detected. PMID- 1942008 TI - Maternal transmission of SIVsmm in rhesus macaques. AB - Fifteen SIV-infected rhesus monkeys delivered 13 livebirths and two stillbirths; one livebirth died at three days of age. While all infants were culture-negative for SIV at birth, nine had maternal antibodies that disappeared by six months of age. Three infants subsequently seroconverted and became virus positive at 9-15 months. Milk samples from all mothers were virus-negative at parturition but samples from four animals were virus-positive at nine and 12 months. This study documents maternal transmission of SIV and suggests transmission by breast feeding. PMID- 1942009 TI - Molecular diversity of SIVsmm/PBj and a cognate variant, SIVsmm/PGg. AB - The molecular diversity of SIVsmm/PBj proviral genomes in tissues of an infected macaque was analyzed. Molecular clones derived directly from intestinal tissue DNA were heterogenous, and contained LTRs with one or two NF-kB binding sites. LTRs with one NF-kB site predominated (approximately 75%). Virions derived from biologically active chimeric DNA clones with one or two NF-kB sites did not induce the acute death syndrome characteristic of PBj infection. These results suggest that either the duplicated NF-kB site acts in concert with other important viral determinants, or plays no role in producing the PBj syndrome. PMID- 1942010 TI - Serial pathogenesis study of SIV brain infection. AB - A serial study of early SIV brain infection revealed initial involvement of leptomeninges, followed by perivascular infection of brain parenchyma. Severity of SIV encephalitis correlated with severity of systemic disease rather than with length of infection. Diffuse white matter disease was not observed, and there was little evidence of SIV infection of brain endothelial cells. SIV infection of leptomeninges is separate from infection of the brain, which appears to be due to transvascular spread of infected monocytes/macrophages. PMID- 1942011 TI - Digital three-dimensional visualization of cellular organelles studied by medium- and high-voltage electron microscopy. AB - Tilted thick sections (one-half to several micrometers) of biological specimens observed with medium- to high-voltage electron microscopes are extremely useful for the study of the three-dimensional (3-D) structure of organelles. If high resolution in 3-D visualization and 3-D reconstruction is needed, many images corresponding to various angles of rotation and tilt must be recorded. This necessitates very time-consuming work--including eventual photographic processing -before good positioning of the object is defined. We have developed software which permits very rapid and precise determination of the tilt-axis, the registration of tilted views, 3-D measurements and 3-D visualization. Images are digitized either from negative films or directly with a camera fitted to the microscope. The application of the software is performed in minutes and allows for a rapid check of the quality of the tilt-series and of the features of interest of the object. Application of the software to the study of the 3-D structure of active components of the nucleolus stained with silver is shown. PMID- 1942012 TI - Type A behavior within families: parents and older adolescent children. AB - Type A behavior has been associated with increased risk of coronary heart disease and occupational stress. However, researchers know very little about the etiology of the Type A behavior pattern (TABP). Relating measures of TABP in the young to comparable measures from their parents and other family members is one way to address the etiological issue. This study is the first in a series which examines the relationship between parent and child TABP using multiple measures for assessing TABP and the same measures in children and their parents. One hundred thirty-eight undergraduate students at the University of Vermont and their parents completed three Type A and two anger measures. The results suggest a cross-gender pattern in which Type A in fathers is related to Type A in their daughters and Type A in mothers is related to Type A in their sons. Anger measures generally agree with this pattern. Methodological difficulties in the field and future directions for research are discussed. PMID- 1942013 TI - Self-efficacy, reasoned action, and oral health behavior reports: a social cognitive approach to compliance. AB - The usefulness of a social cognitive approach to compliance with brushing and flossing behavior recommendations was tested with 39 patients recruited from the State University of New York at Buffalo Periodontal Disease Clinical Research Center. Participants completed mailed study instruments assessing Fishbein and Ajzen's theory of reasoned action variables, Bandura's self-efficacy variables, and frequency of brushing and flossing behavior. Results indicated positive attitudes, beliefs, and norms for brushing and flossing and positive intentions to brush but less intention to floss. Hierarchical regression analyses supported the basic usefulness of the theory of reasoned action for oral health behavior reports. Addition of self-efficacy variables to theory of reasoned action variables significantly increased the explained variance of brushing and flossing behavior reports. These results establish a strong basis for future clinical studies investigating social cognitions and the prediction of oral health behavior. PMID- 1942014 TI - Relative effectiveness of methods of breast self-examination. AB - This study investigated the effectiveness of different methods of breast self examination (BSE) on coverage of breast area and lump detection, using a factorial design, pairing three search patterns (concentric circle, radial spoke, vertical strip) with two finger palpation techniques (small circular movements, sliding movements). Ninety-seven female undergraduates were randomly assigned to one of six BSE training conditions which were identical except in the BSE search pattern and finger palpation technique explained by the instructor. Following the 20-min, small-group training, subjects' coverage of breast area was assessed by scoring their BSE performance on a breast board. Lump detection was determined by the number of lumps correctly identified in silicone breast models. Results indicated that the vertical strip pattern was associated with significantly greater coverage of the breast area. There were no significant differences in lump detection; however, the sliding finger palpation technique resulted in significantly more false identifications of lumps. PMID- 1942015 TI - The utility of the Psychosomatic Symptom Checklist among hospitalized patients. AB - We examined the utility of the Psychosomatic Symptom Checklist in an inpatient medical setting with particular emphasis on the putative ability of the PSC to discriminate psychosomatic from nonpsychosomatic patients. First, 80 hospitalized psychosomatic patients were compared to 80 hospitalized medical patients on the PSC. Second, a sample of 187 psychosomatic patients was studied to examine the relationship among psychosomatic distress, depression, and functional impairment. The results indicate that while psychosomatic patients scored significantly higher than comparable medical patients on the PSC, discriminant analyses indicate that the PSC is not able to identify psychosomatic patients in an inpatient medical setting. Factor analyses and correlations show that the PSC is positively related to increased depression and decreased functional status. Results are interpreted in light of current psychosomatic theory. PMID- 1942016 TI - Situational factors and patterns associated with smokeless tobacco use. AB - Situational factors and topographic features associated with smokeless tobacco use were examined. Male smokeless tobacco users (N = 30) were asked to record the time, activity, and internal states associated with each dip of tobacco use over the course of 10 days. Additionally, these subjects were asked to record the activity and internal state they were experiencing every hour for a 15-hr waking period to obtain baseline rates of these events. Serum and saliva samples were obtained to measure cotinine concentrations. The activities significantly associated with smokeless tobacco use included after a meal, while driving, and while watching television. The internal states associated with smokeless tobacco use were feeling relaxed and depressed. Factor analysis of the events showed factors which are different from those found among cigarette smokers. Examination of the topographic measures of smokeless tobacco use showed that the total dip duration per day was 283.5 min, with a range of 79.7-757.1 min. This measure, along with duration of dipping time (time from onset to offset of smokeless tobacco use during the day), may be the best predictors of nicotine exposure. PMID- 1942017 TI - Underestimates of student substance use by school personnel: a cause for concern? AB - The present study was designed to compare school personnel's (i.e., principals, counselors, teachers) estimates of student substance use with student self reported data. Comparisons were made in 78 schools between 5431 student self reports of tobacco, alcohol, and drug use and 170 school personnel's estimates of student substance use. The results indicated that a significant number of school personnel were unable to estimate student substance use. Personnel who did provide estimates typically underestimated the degree of substance use, in comparison to student self-reported substance use. School personnel did not significantly overestimate use in comparison to student self-reported substance use for any substance in any grade or geographic area. It is suggested that school personnel may resist the adoption of prevention programs because of a perceived lack of need due to underestimation of the substance use problem. PMID- 1942019 TI - Brief report: an empirically derived educational program for detecting and preventing skin cancer. AB - College and high-school students were administered a questionnaire to assess their knowledge about skin cancer, and afterward an educational program was designed to correct the identified deficiencies. Results showed that the students were relatively uniformed about how to recognize and prevent skin cancer--high school students more so than college students--but that their knowledge of the disease (e.g., risk factors, preventive measures, and identification of "warning signs" for early detection) increased significantly after training. Some forgetting was noted at a 2-week follow-up but knowledge levels were still significantly higher than baseline. If these findings are representative of the general population, more preventive education will be needed in this area. This is especially true because the potentially deadly melanoma appears to be increasing at an alarming rate. PMID- 1942018 TI - Whether to measure change from baseline or absolute level in studies of children's cardiovascular reactivity: a two-year follow-up. AB - Blood pressure and heart rate were measured at rest and during a television video game in 399 healthy children. At the first assessment, children were in third grade and at the 2-year follow-up, they were in fifth grade. Children were classified according to race (black/white), gender (boy/girl), body mass index (light/heavy), and video game performance (low score/high score). Correlational analysis indicated that irrespective of the classification variable, absolute reactivity values, e.g., a heart rate of 110 bpm, tended to be more stable than change reactivity values, e.g., a heart rate change of 10 bpm. The greater stability of absolute values was most pronounced with systolic blood pressure. Absolute values were at least as stable as resting values and frequently demonstrated greater stability. Mean and maximal reactivities were correlated comparably. We conclude that children's reactivity is a stable characteristic and that, unless indicated by a priori hypotheses, the use of absolute values is preferable to the use of change values. PMID- 1942020 TI - Necrotizing fasciitis. PMID- 1942021 TI - Construction of an electrode for intraoperative nerve stimulation. AB - The electrode described in this paper consist of a barrel or handle with its conducting cable and a detachable stimulating tip. It is constructed of inexpensive and commercially available materials and is disposable. During the course of a stimulation study, electrode tips of different lengths or curvatures may be substituted without the need to replace the electrode barrel and cable. PMID- 1942022 TI - Reforming Medicare payments: the RBRVS. PMID- 1942023 TI - Anabolic steroids: another form of drug abuse. PMID- 1942024 TI - Protection of the unstable spine during transport and early hospitalization. PMID- 1942025 TI - Gay. PMID- 1942026 TI - Crystallization and preliminary X-ray crystallographic analysis of verotoxin-1 B subunit. AB - The B-subunit of verotoxin-1, which is believed to form a pentamer (monomer Mr = 7691), has been crystallized by vapor diffusion over a wide range of conditions. The best crystals, obtained with polyethylene glycol 8000 as the precipitant, belong to the orthorhombic space group P2(1)2(1)2(1), with cell dimensions a = 59.2 A, b = 102.7 A, c = 56.3 A. The cell dimensions are consistent with one B subunit pentamer per asymmetric unit, and the crystals diffract to at least 2.0 A resolution. Data collected using synchrotron radiation at a wavelength of 2.070 A may allow the structure to be solved using the anomalous signal from three sulfur atoms in the monomer, combined with averaging over the non-crystallographic symmetry. PMID- 1942027 TI - Evidence for an ancestral core structure in nucleotide-binding proteins with the type A motif. AB - Many proteins that bind purine nucleotide triphosphates have a type A sequence motif. Only two classes of structures for such proteins are so far available from X-ray crystallography. We examined the tertiary structures of representatives of the two classes, porcine cytoplasmic adenylate kinase and Escherichia coli translational elongation factor Tu. Comparison of the two proteins suggests that the A motif may be just one part of a larger common core structure consisting of four parallel strands of beta-sheet sandwiched between four alpha-helices. This compact core structure comprises over one half of each protein. We speculate that A motif proteins have diverged from a common ancestor having this core structure. PMID- 1942028 TI - Structural parameters of the Pf1 gene 5 protein-DNA complex in solution by neutron scattering. AB - Neutron-scattering experiments have been performed on the intracellular complex formed by the gene 5 protein and single-stranded DNA in cells infected by filamentous bacteriophage Pf1. The contrast matched point of the complex (37% 2H2O) is lower than expected and implies that a substantial fraction of potentially labile hydrogen atoms are unable to exchange with the solvent. The mass/length ratio of the complex (3270 daltons/A) indicates an axial subunit repeat of 5.1 A, a value much larger than the subunit repeat previously determined in fibres. The measured value of the cross-sectional radius of gyration at infinite contrast (Rc = 43.3 A) indicates an outer radius of 60 to 63 A for the complex. The variation in Rc with contrast shows that regions of higher scattering density are located, on average, towards the outside of the complex. The high-angle region of the intensity curve (measured in 2H2O) reveals a clear subsidiary maximum at 0.105 A-1 arising from the 60 A helical pitch of the nucleoprotein complex. The structural parameters of the Pf1 gene 5 protein-DNA complex in solution are compared with those of the fd gene 5 protein-DNA complex. PMID- 1942029 TI - Crystal structure analysis of oxidized Pseudomonas aeruginosa azurin at pH 5.5 and pH 9.0. A pH-induced conformational transition involves a peptide bond flip. AB - The X-ray crystal structure of recombinant wild-type azurin from Pseudomonas aeruginosa was determined by difference Fourier techniques using phases derived from the structure of the mutant His35Leu. Two data sets were collected from a single crystal of oxidized azurin soaked in mother liquor buffered at pH 5.5 and pH 9.0, respectively. Both data sets extend to 1.93 A resolution. The two pH forms were refined independently to crystallographic R-factors of 17.6% (pH 5.5) and 17.5% (pH 9.0). The conformational transition previously attributed to the protonation/deprotonation of residue His35 (pKa(red) = 7.3, pKa(ox) = 6.2), which lies in a crevice of the protein close to the copper binding site, involves a concomitant Pro36-Gly37 main-chain peptide bond flip. At the lower pH, the protonated imidazole N delta 1 of His35 forms a strong hydrogen bond with the carbonyl oxygen from Pro36, while at alkaline pH the deprotonated N delta 1 acts as an acceptor of a weak hydrogen bond from HN Gly37. The structure of the remainder of the azurin molecule, including the copper binding site, is not significantly affected by this transition. PMID- 1942030 TI - Preparation and X-ray characterization of four new crystal forms of jacalin, a lectin from Artocarpus integrifolia. AB - Four new crystal forms of the anti-T lectin from jackfruit (Artocarpus integrifolia) have been prepared and characterized. Three of them, two monoclinic (P21, a = 59.4 A, b = 83.3 A, c = 63.5 A, beta = 107.7 degrees; C2, a = 106.1 A, b = 53.9 A, c = 128.0 A, beta = 95.0 A) and one orthorhombic (C222(1), a = 98.1 A, b = 67.3 A, c = 95.1 A) were grown with 2-methylpentan-2,4-diol (MPD) as the precipitant while the fourth, an hexagonal form (P6(1)22, a = b = 129.6 A, c = 157.9 A), was obtained in the presence of methyl-alpha-D-galactopyranoside with polyethylene glycol 4000 as the precipitant. The reported relative molecular mass (Mr) of the lectin was found to be inconsistent with the solvent content of the crystals estimated using measured densities. The Mr was redetermined using size exclusion chromatography in the presence of methyl-alpha-D-galactopyranoside and Ferguson-plot analysis of mobilities in polyacrylamide gel electrophoresis. The redetermined Mr (66,000) is consistent with the measured crystal densities. The orthorhombic and the hexagonal forms, which have one half molecule and one molecule, respectively, in the asymmetric unit, are suitable for high-resolution X-ray analysis. PMID- 1942031 TI - An in vitro approach to identifying specificity determinants of mutagenesis mediated by DNA misalignments. AB - In vitro, misalignments of the newly synthesized (primer) strand during DNA polymerization lead to deletion and/or complex frameshift mutations. In vivo, similar misalignments of repeated and quasipalindromic DNA sequences are predicted to be intermediates of mutagenesis. The mutagenic misalignments are mediated by complementary pairing between the sequence at the 3'-OH end of the newly synthesized DNA strand and sequences in the template or in the newly synthesized DNA. Mutant sequences are produced when the misaligned primers act as substrates for DNA polymerization. The misalignments responsible for detected mutant sequences were compared to similar misalignments that were not implicated in mutagenesis, and all misalignment possibilities were compared to the position of pausing during polymerization by Escherichia coli polymerase I or its Klenow fragment. These comparisons revealed three characteristics of in vitro misalignment specificity. First, the termini produced by pausing are likely to be precursors to mutagenic misalignments. Second, the absence of some potential misalignments from the detected spectrum is explained well by the predicted undetectability of the mutant sequences they produce. Third, factors distinct from pausing and mutant detectability are responsible for differences in the specificity of misalignment mutagenesis mediated by E. coli DNA polymerase I and Klenow polymerase during in vitro synthesis. PMID- 1942032 TI - Variant specific glycoprotein of Trypanosoma brucei consists of two domains each having an independently conserved pattern of cysteine residues. AB - The complete amino acid sequences for nine variant specific glycoproteins (VSGs) of Trypanosoma brucei are presented. These have more than doubled the size of the VSG sequence data base and have enabled a new and more rigorous comparison to be made between amino acid sequences of different VSGs. Each VSG can be defined as a combination of an N-terminal domain type and a C-terminal domain type, based on the distribution of cysteine residues within the molecule. This identifies three N-terminal domain types and at least four C-terminal domain types. Different combinations of N and C-terminal domains can be formed; for example, in the sequences presented here, two different N-terminal domains are found in association with each of three different C-terminal domains. The biological context of the domain structure of VSGs is discussed. PMID- 1942033 TI - Determination of an RNA structure involved in splicing inhibition of a muscle specific exon. AB - We have investigated the RNA structure of the region surrounding the muscle specific exon 6B of the chicken beta-tropomyosin gene. We have used a variety of chemical and enzymatic probes: dimethylsulfate, N-cyclohexyl-N'-(2-(N methylmorpholino)-ethyl)-carbodiimide-p-tolu enesulfonate) , RNase T1 and RNase V1. Lead acetate was also used to obtain some information on the tertiary structure of this region. Probing the wild-type sequence suggests a model involving one-stem and three-stem-loop structures in and around this exon. Two of these, hairpin I and stem III, have previously been implicated in repression of splicing of the intron following exon 6B in a HeLa nuclear extract. Stem I includes sequences at the beginning of exon 6B and stem III results from interaction of the intron upstream from exon 6B with sequences in the middle of the intron downstream from this exon (the intron whose splicing is repressed). Neither stem I nor stem III directly involves the consensus sequences (5' splice site, branch-point, 3' splice site) of the repressed intron. Probing RNAs that are derepressed for splicing of this intron show that there are structural changes around the 5' splice site and branch-point sequence that correlate with the derepression. This is true, despite the fact that the derepressed RNAs are altered in a region far from these consensus sequences. The most striking structural correlation with splicing capacity of the intron downstream from exon 6B is seen by probing with lead acetate. Lead ions cut RNA at specific residues; these sites are very sensitive to RNA tertiary structure. Repressed and derepressed RNAs show entirely different cleavage patterns after incubation with lead acetate. Remarkably, hybridizing a derepressed RNA with an RNA comprising the ascending arm of stem III not only re-establishes repression, but also converts the pattern of susceptibility to attack by lead ions over the whole molecule. We suggest that RNA conformation plays a role in keeping exon 6B from being spliced into non-muscle cell mRNA. PMID- 1942034 TI - Cumulative site-directed charge-change replacements in bacteriophage T4 lysozyme suggest that long-range electrostatic interactions contribute little to protein stability. AB - Bacteriophage T4 lysozyme is a basic molecule with an isoelectric point above 9.0, and an excess of nine positive charges at neutral pH. It might be expected that it would be energetically costly to bring these out-of-balance charges from the extended, unfolded, form of the protein into the compact folded state. To determine the contribution of such long-range electrostatic interactions to the stability of the protein, five positively charged surface residues, Lys16, Arg119, Lys135, Lys147 and Arg154, were individually replaced with glutamic acid. Eight selected double, triple and quadruple mutants were also constructed so as to sequentially reduce the out-of-balance formal charge on the molecule from +9 to +1 units. Each of the five single variant proteins was crystallized and high resolution X-ray analysis confirmed that each mutant structure was, in general, very similar to the wild-type. In the case of R154E, however, the Arg154 to Glu replacement caused a rearrangement in which Asp127 replaced Glu128 as the capping residue of a nearby alpha-helix. The thermal stabilities of all 13 variant proteins were found to be fairly similar, ranging from 0.5 kcal/mol more stable than wild-type to 1.7 kcal/mol less stable than wild-type. In the case of the five single charge-change variants, for which the structures were determined, the changes in stability can be rationalized in terms of changes in local interactions at the site of the replacement. There is no evidence that the reduction in the out-of-balance charge on the molecule increases the stability of the folded relative to the unfolded form, either at pH 2.8 or at pH 5.3. This indicates that long-range electrostatic interactions between the substituted amino acid residues and other charged groups on the surface of the molecule are weak or non-existent. Furthermore, the relative stabilities of the multiple charge replacement mutant proteins were found to be almost exactly equal to the sums of the relative stabilities of the constituent single mutant proteins. This also clearly indicates that the electrostatic interactions between the replaced charges are negligibly small. The activities of the charge-change mutant lysozymes, as measured by the rate of hydrolysis of cell wall suspensions, are essentially equal to that of the wild-type lysozyme, but on a lysoplate assay the mutant enzymes appear to have higher activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1942035 TI - Computer modeling 16 S ribosomal RNA. AB - A three-dimensional structure for 16 S RNA has been produced with a computer protocol that is not dependent on human intervention. This protocol improves upon traditional modeling techniques by using distance geometry to fold the molecule in an objective and reproducible fashion. The method is based on the secondary structure of RNA and treats the molecule as a set of double-stranded helices that are linked by flexible single-strands of variable length. Data derived from chemical cross-linking studies of 16 S RNA and tertiary phylogenetic relationships provide the constraints used to fold the molecule into a compact three-dimensional form. Possibly subjective evaluation of the input data are transformed into verifiable quantitative parameters. Relationships based on general locations within the 30 S subunit or on protein-RNA interactions have been specifically excluded. The resolution of the model exceeds that of electron micrographs and approaches that obtained in preliminary X-ray crystal structures. The model size of 245 x 190 x 140 A is compatible with that of the 30 S subunit as determined by electron microscopy. The volume of the model is 1.87 x 10(6) A which is similar to that of the small subunit in a preliminary X-ray crystal structure. The radius of gyration of the model structure of 76 A is intermediate to that seen for partially denatured and fully folded 16 S RNA. Computer graphics are used to display the results in a manner that maximizes the opportunities for human visual interpretation of the models. A format for displaying the structures has been developed that will make it possible for researchers who have not devoted themselves to ribosomal modeling to comprehend and make use of the information that the models embody. On this basis the computer-generated models are compared with models developed by other researchers and with structural data not included in the folding parameter data set. PMID- 1942036 TI - Refined crystal structures of "aged" and "non-aged" organophosphoryl conjugates of gamma-chymotrypsin. AB - "Aged" organophosphoryl conjugates of serine hydrolases differ from the corresponding "non-aged" conjugates in their striking resistance to nucleophilic reactivation. The refined X-ray structures of "aged" and "non-aged" organophosphoryl conjugates of gamma-chymotrypsin were compared in order to understand the molecular basis for this resistance of "aged" conjugates. "Aged" and "non-aged" crystalline organophosphoryl-gamma-chymotrypsin conjugates were obtained by prolonged soaking of native gamma-chymotrypsin crystals with appropriate organophosphates. Thus, a representative "non-aged" conjugate, diethylphosphoryl-gamma-chymotrypsin, was obtained by soaking native crystals with paraoxon (diethyl-p-nitrophenyl phosphate), and a closely related "aged" conjugate, monoisopropyl-gamma-chymotrypsin, was obtained by soaking with diisopropylphosphorofluoridate. In both crystalline conjugates, the refined structures clearly reveal a high occupancy of the active site by the appropriate organophosphoryl moiety within covalent bonding distance of Ser195 O gamma. Whereas in the "non-aged" conjugate both ethyl groups can be visualized clearly, in the putative "aged" conjugate, as expected, only one isopropyl group is present. There is virtually no difference between the "aged" and "non-aged" conjugates either with respect to the conformation of the polypeptide backbone as a whole or with respect to the positioning of the side-chains within the active site. In the "aged" conjugate, however, close proximity (2.6 A) of the negatively charged phosphate oxygen atom of the dealkylated organophosphoryl group to His57 N epsilon 2 indicates the presence of a salt bridge between these two moieties. In contrast, in the "non-aged" conjugate the DEP moiety retains its two alkyl groups; thus, lacking a negative oxygen atom, it does not enter into such a charge-charge interaction and its nearest oxygen atom is 3.6 A away from His57 N epsilon 2. It is suggested that steric constraints imposed by the salt bridge in the "aged" conjugate lie at the basis of its resistance to reactivation. PMID- 1942037 TI - Groove-backbone interaction in B-DNA. Implication for DNA condensation and recombination. AB - DNA self-fitting is revealed by the study of intermolecular contacts found in the crystal packing of a dodecamer where the helices are locked together by a reciprocal groove-backbone interaction and form a crossed structure. It is proposed that it could be a model for DNA-DNA interaction in several biological processes such as the node of supercoiled DNA and synapsis in recombination. The main topological and symmetrical features of this crossed structure are described and the symmetry-homology relationships are analyzed in the more general case of B-DNA interacting helices. Model-building of Holliday junctions with minimal change from the starting crystal coordinates of the crossed structure leads to at least three different solutions. These various models are compared from the point of view of their symmetry and topology, in the light of their branch migration and resolution properties. In addition, a model for a self-favored reciprocal unwinding mechanism based on the experimentally observed structural alterations, such as the packing-induced opening of G.C base-pairs is proposed. In this model, the phosphate groups of the invading backbone trigger the opening of the base pairs of the other helix, by pulling cytosine or adenine bases out of the major groove after binding to their amino group. PMID- 1942038 TI - Crystal structure of uncleaved ovalbumin at 1.95 A resolution. AB - Ovalbumin, the major protein in avian egg-white, is a non-inhibitory member of the serine protease inhibitor (serpin) superfamily. The crystal structure of uncleaved, hen ovalbumin was solved by the molecular replacement method using the structure of plakalbumin, a proteolytically cleaved form of ovalbumin, as a starting model. The final refined model, including four ovalbumin molecules, 678 water molecules and a single metal ion, has a crystallographic R-factor of 17.4% for all reflections between 6.0 and 1.95 A resolution. The root-mean-square deviation from ideal values in bond lengths is 0.02 A and in bond angles is 2.9 degrees. This is the first crystal structure of a member of the serpin family in an uncleaved form. Surprisingly, the peptide that is homologous to the reactive centre of inhibitory serpins adopts an alpha-helical conformation. The implications for the mechanism of inhibition of the inhibitory members of the family is discussed. PMID- 1942039 TI - Prediction of protein backbone conformation based on seven structure assignments. Influence of local interactions. AB - A method is developed to compute backbone tertiary folds from the amino acid sequence. In this method, the number of degrees of freedom is drastically reduced by neglecting side-chain flexibility, and by describing backbone conformations as combinations of only seven structural states. These are characterized by single values of the dihedral angles phi, psi and omega, representing allowed conformations of the isolated dipeptide. We show that this restrictive model is none the less capable of describing native backbones to within acceptable deviations. Using our backbone description, potentials of mean force are derived from a database of known protein structures, based on statistical influences of single residues and residue pairs on the conformational states in their vicinity along the chain. This yields the force-field component due to local interactions, which is then used to predict lowest-energy conformations from any given amino acid sequence. The prediction algorithm does not require searching conformational space and is therefore extremely fast. Another important asset of our method is that it is able to compute not only the minimum energy conformation, but any number of lowest energy structures, whose relative preferences can be determined from the corresponding computed energy values. The performance of our procedure is tested on short peptides that are likely to be stabilized by local interactions. These include several helical structures and a hexapeptide with a beta-bend conformation, corresponding to peptides shown to have relatively well defined conformations in aqueous solution, and to protein segments believed to adopt their native conformation early during folding. In addition, several flexible peptides are analysed. Except for the problems encountered in predicting observed disulphide bridges in two of the flexible peptides, and in a somewhat larger fragment comprising residues 30 to 51 of bovine trypsin inhibitor, prediction results compare very favourably with experimental data. Potential applications of our procedure to protein modelling and its extension to protein folding are discussed. PMID- 1942040 TI - A study of electrophoretic mobility of DNA in agarose and polyacrylamide gels. AB - The aim of this paper is to clarify the mechanism of gel electrophoresis of DNA under constant-field conditions. We have conducted a large number of experiments on double-stranded DNA varying in length between approximately 10 and approximately 50,000 base-pairs, in both agarose and polyacrylamide gels ranging from 0.5% to 12% concentration, and with electric field strengths ranging from 0.5 to 8 V/cm. We have made (logarithmic) plots of velocity against length of DNA for all of the various test conditions. At the left-hand side of these plots, all of the empirical curves have a unique, standard shape. When the curves are normalized so that their left-hand parts coincide, a second feature emerges in that, while for any given test the curve follows the "master curve" up to a certain point, it then "breaks away" and becomes horizontal. We describe these two patterns of behaviour as "regions 1 and 2", respectively. We find simple yet comprehensive empirical formulae that fit the observations in the two regions of behaviour: these express the velocity in terms of length of DNA, electric field strength and gel concentration. We then construct two separate theories for the two regions of behaviour. The first theory involves the statistics of motion of an object through a random array of gel obstacles, with the instantaneous speed depending on the number of obstacles with which the object is currently in contact. The second theory is based on the mechanical hypothesis (for which there is other, independent support) that the DNA moves through the gel by piling up against a barrier, which eventually breaks or deforms under the resulting force, thereby allowing the DNA to move on to the next barrier. The statistical theory is an adaptation of existing work, while the mechanical one is new. We also describe experiments on the migration of repeated-sequence, curved DNA with length up to 1500 base-pairs, and we discuss its behaviour in terms of our two theories. Our studies by electron microscopy are consistent with the view that this repeated-sequence DNA adopts a superhelical configuration. Finally, we show that a very wide range of observations may be understood clearly by means of our two theoretical schemes. PMID- 1942041 TI - Crystallization and preliminary X-ray investigation of a sarcoplasmic calcium binding protein from amphioxus. AB - Crystals of a sarcoplasmic Ca(2+)-binding protein from the protochordate amphioxus have been grown from solutions of ammonium sulfate. The crystals are orthorhombic, space group C222(1), with unit cell axes a = 59.6(1) A, b = 81.3(1) A and c = 82.4(1) A. There is one molecule in the asymmetric unit. The crystals diffract beyond 2.5 A and show less than 20% decline in diffraction intensities after a three day exposure to X-rays from a laboratory rotating anode source. PMID- 1942042 TI - Crystallization and crystal packing of Proteus mirabilis PR catalase. AB - The tetrameric catalase from Proteus mirabilis PR (EC 1.11.1.6), known to bind NADPH, has been crystallized by the hanging-drop method in a form apparently depleted in dinucleotide. The crystals belong to the hexagonal space group P6(2)22 with a = b = 111.7 A, c = 248.8 A. There is one subunit in the asymmetric unit. Data were collected to 2.9 A at the L.U.R.E. (Orsay) synchrotron radiation facility. The tetramers have been located in the crystal, centered on the site (1/2, 0, 0) with 222 symmetry. PMID- 1942043 TI - Crystallization of the IIA domain of the glucose permease of Bacillus subtilis. AB - The IIA domain of the glucose permease of the phosphoenolpyruvate: sugar phosphotransferase system (PTS) from Bacillus subtilis has been crystallized. Crystals are obtained from ammonium sulfate solution. They diffract to at least 2.2 A resolution, and belong to space group C222(1), with unit cell dimensions: a = 74.2 A; b = 54.9 A; c = 67.0 A. PMID- 1942044 TI - Studies on the interaction of T7 RNA polymerase with a DNA template containing a site-specifically placed psoralen cross-link. I. Characterization of elongation complexes. AB - A 66 base-pair (bp) DNA template carrying a site-specifically placed psoralen cross-link downstream from a phage T7 promoter was constructed. This template can support transcription by T7 RNA polymerase. Transcription was blocked specifically at the psoralen cross-link. We studied the characteristics of elongation complexes, formed in this manner, by enzymatic and chemical footprinting and by a nitrocellulose filter-binding assay. The DNase I footprint of the elongation complex was quantified on a residue by residue basis. It was found that T7 RNA polymerase made the strongest contacts in the central region of the footprint whereas the leading and lagging edges of the polymerase were weakly bound to the DNA. Reducing the NaCl concentration in the transcription reaction resulted in the visualization of two T7 RNA polymerase molecules bound to the same template. A leading polymerase molecule, arrested at the psoralen cross link, showed a much smaller DNase I footprint than a lagging polymerase molecule that was bound upstream. This upstream polymerase molecule occupied approximately one-half of the promoter region and therefore did not achieve complete promoter clearance. These experiments suggest that complete promoter clearance is required for a gross conformational change in the polymerase, consisting of a contraction in the size of its footprint to occur. DNase I footprinting also revealed that an elongation complex arrested at a psoralen cross-link undergoes several subtle changes in structure in a time-dependent manner and therefore can be considered to be in a state of dynamic flux. Methylation protection showed that some G residues in the top (non-coding) strand are protected against attack by dimethylsulfate, whereas the G residues on the bottom (coding) strand appear not to be protected from reaction with dimethylsulfate. We probed the transcribing complexes for single-stranded regions with T7 gene 3 endonuclease. From the pattern of sensitivity to T7 gene 3 endonuclease on the template strand, we conclude that the RNA-DNA hybrid in the elongation complex is about 7 bp. A nitrocellulose filter-binding assay showed that the elongation complex, consisting of a 36 (+1) nucleotide RNA, the 66 bp DNA template and the T7 RNA polymerase was stable for at least 30 minutes at high salt concentrations. Heparin caused the quantitative release of 36 (+1) RNA nucleotides within 30 seconds, but the DNA was not simultaneously released from the elongation complex under these conditions. PMID- 1942046 TI - Function of P11, a tertiary base pairing in self-splicing introns of subgroup IA. AB - There is phylogenetic evidence for the existence of a new pairing in subgroup IA1 self-splicing introns. This tertiary interaction, called P11, which is extraneous to the catalytic centre of these ribozymes was modelled after a "pseudoknot" and grafted by computer modelling on the common core structure of group I introns that was recently proposed by Michel & Westhof. In order to probe the function of the P11 pairing, we mutated the P11 helix in the intron of the large ribosomal precursor of Saccharomyces cerevisiae mitochondria (Sc.LSU). Our experimental data show that the P11 pairing plays a role in stabilizing the overall fold of the RNA molecule. While P11 is not essential for self-splicing activity in vitro, mutants with disrupted P11 require higher concentration of MgCl2 for self splicing. By contrast, mutants with a reinforced P11 pairing (via introduction of several G.C base-pairs) self-splice more efficiently than the wild-type at 55 degrees C. Based on this work, the possible engineering of new stable versions of the ribozyme is discussed. PMID- 1942045 TI - Studies on the interaction of T7 RNA polymerase with a DNA template containing a site-specifically placed psoralen cross-link. II. Stability and some properties of elongation complexes. AB - We constructed a 66 base-pair DNA template capable of supporting transcription by T7 RNA polymerase. This template had a psoralen cross-link downstream from a T7 promoter such that a 36 (+1) nucleotide transcript was synthesized at the time the T7 polymerase came to a stop at the cross-link. The stability of elongation complexes formed on this template, and the effect of different factors that are known to affect polymerase-DNA interactions was investigated by non-denaturing gel electrophoresis and gel filtration chromatography. We found that an elongation complex could lose its RNA component but the T7 polymerase still remained attached to the DNA template for extended periods of time (at least up to 18 h). This type of an elongation complex, bereft of its nascent RNA transcript, is called a quasi-elongation complex. DNase I footprinting within gel slices indicated that the polymerase molecules were arrested at the psoralen cross-link on the DNA template in the quasi-elongation complexes. The quasi elongation complexes were found to be extremely stable in 0.5 M-NaCl and in 0.2 M NaCl plus 60 mM-MgCl2, and could withstand temperatures up to 42 degrees C. The quasi-elongation complexes were destabilized by heparin and excess calf thymus DNA. Excess tRNA caused only a minimal degree of disruption. Non-promoter containing plasmid DNAs did not have a destabilizing effect on the quasi elongation complexes. Interestingly, it was observed that in a T7 ternary transcriptional complex arrested by a psoralen cross-link, the nascent RNA transcript could be stabilized from release by the presence in trans of a plasmid DNA bearing a T7 promoter and a T7 terminator. Such a stabilization against RNA release was not observed with plasmid DNAs containing either only a promoter or a terminator. The elongation complexes were stable during gel filtration through Sephacryl S-300 HR. However, it was found that 30% to 45% of the labeled RNA was retained during gel filtration as RNA that was apparently free from ternary complexes. PMID- 1942047 TI - The Staphylococcus aureus mutation pcrA3 leads to the accumulation of pT181 replication initiation complexes. AB - In Staphylococcus aureus cells carrying the pcrA3 chromosomal mutation, plasmid pT181 and its derivatives were maintained at a reduced copy number. A significant proportion of their DNA migrated during agarose gel electrophoresis as nicked DNA. The results obtained in the characterization of this plasmid DNA species show that it represents replication initiation complexes. Such complexes could not be detected in a wild-type host. The replication initiation complexes present in pcrA3 cells could resume replication after a lag. It was concluded from these results that the pcrA3 host mutation affected a step in plasmid pT181 replication immediately following the formation of the replication initiation complex, and that in pcrA3 this step became rate-limiting for plasmid pT181 replication. PMID- 1942048 TI - Mitochondrial D-loop sequences are integrated in the rat nuclear genome. AB - We have cloned two fragments of rat nuclear DNA (nucDNA), 3.3 x 10(3) nucleotide pairs (knp) and 9.1 knp, that contain a 0.5 knp section sharing 80% sequence identity with the mitochondrial DNA (mtDNA) heavy strand origin of replication (D loop) nascent strand and 88% identity with each other. The light and heavy strand promoters of the D-loop region are not present in either clone, thus they likely do not function as replication origins in the nuclear genome. The nucDNA sequences surrounding the mtDNA-like sequences are not mitochondrial, thus the mtDNA-like sequences are demonstrably covalently linked in the nuclear genome. Indeed, the surrounding nuclear sequences of each clone also share 88% identity. This sequence arrangement strongly suggests an initial insertion of mtDNA into nucDNA with subsequent amplification of an encompassing region of nucDNA. Divergence calculations suggest that the mtDNA insertion occurred around 13.6 million years ago (MYA) with the subsequent separation occurring around 6.5 MYA. The mtDNA-like sequences of the nuclear clones hybridize strongly to a number of different BamHI-PstI restriction fragments, suggesting either repeated integration and/or frequent mutational events producing new restriction enzyme sites. It is not yet known if one or more of the uncloned D-loop-like sequences are associated with promoters, which would suggest possible function. The 3.3 knp nucDNA fragment is present in low copy number. In contrast, the 9.1 knp nucDNA fragment appears to be moderately repeated. The elements do not appear to be tandemly repeated. The nucDNA clones contain remnants of rat long interspersed repetitive element (LINE) sequences; in addition the 9.1 knp fragment contains sequences with similarity to portions of viral reverse transcriptase and RNaseH genes. Until now, all mtDNA-like sequences found in the nuclear genome have been coding sequences. This is the first confirmation by sequence analysis of a portion of the mtDNA control region in the nuclear genome. PMID- 1942049 TI - Sporulation operon spoIVF and the characterization of mutations that uncouple mother-cell from forespore gene expression in Bacillus subtilis. AB - During the process of endospore formation in Bacillus subtilis the appearance of the mother-cell transcription factor sigma K by conversion from its inactive precursor pro-sigma K is coupled to events under the control of the forespore transcription factor sigma G. This intercompartmental coupling is believed to be mediated by the products of a sporulation locus called spoI V F because certain bypass-of-forespore (bof) mutations that map at the spoI V F locus relieve the dependence of pro-sigma K processing on the action of sigma G in the forespore. We now report that spoI V F is a two-cistron operon whose transcription is under the control of the sporulation transcription factor sigma E and whose products are likely to be integral membrane proteins. We show that the products of both the promoter-proximal (spoI V F A) and promoter-distal (spoI V F B) cistrons are required for spore formation at 37 degrees C, but that the spoI V F A gene product is dispensable at 30 degrees C. The bypass-of-forespore mutations are located at the extreme 3' end of the spoI V F A cistron, one such mutation causing a proline to serine substitution eight residues from the COOH terminus of SpoIVFA and another (a nonsense mutation) causing the absence of the terminal six amino acid residues of the protein. We also show that at a permissive temperature for spore formation spoI V F A null mutants exhibit a bypass-of-forespore phenotype. We hypothesize that SpoIVFA functions positively in stabilizing SpoIVFB, which we propose is thermolabile in the absence of the promoter-proximal gene product, and negatively in inhibiting the action of SpoIVFB. A model for intercompartmental coupling is presented in which SpoIVFB promotes pro-sigma K processing in response to a signal from the forespore that relieves or otherwise counteracts the inhibitory effect of SpoIVFA on SpoIVFB. PMID- 1942050 TI - Recognition of the highly conserved GTPase center of 23 S ribosomal RNA by ribosomal protein L11 and the antibiotic thiostrepton. AB - The antibiotic thiostrepton, a thiazole-containing peptide, inhibits translation and ribosomal GTPase activity by binding directly to a limited and highly conserved region of the large subunit ribosomal RNA termed the GTPase center. We have previously used a filter binding assay to examine the binding of ribosomal protein L11 to a set of ribosomal RNA fragments encompassing the Escherichia coli GTPase center sequence. We show here that thiostrepton binding to the same RNA fragments can also be detected in a filter binding assay. Binding is relatively independent of monovalent salt concentration and temperature but requires a minimum Mg2+ concentration of about 0.5 mM. To help determine the RNA features recognized by L11 and thiostrepton, a set of over 40 RNA sequence variants was prepared which, taken together, change every nucleotide within the 1051 to 1108 recognition domain while preserving the known secondary structure of the RNA. Binding constants for L11 and thiostrepton interaction with these RNAs were measured. Only a small number of sequence variants had more than fivefold effects on L11 binding affinities, and most of these were clustered around a junction of helical segments. These same mutants had similar effects on thiostrepton binding, but more than half of the other sequence changes substantially reduced thiostrepton binding. On the basis of these data and chemical modification studies of this RNA domain in the literature, we propose that L11 makes few, if any, contacts with RNA bases, but recognizes the three-dimensional conformation of the RNA backbone. We also argue from the data that thiostrepton is probably sensitive to small changes in RNA conformation. The results are discussed in terms of a model in which conformational flexibility of the GTPase center RNA is functionally important during the ribosome elongation cycle. PMID- 1942051 TI - Refined crystal structure of Cd, Zn metallothionein at 2.0 A resolution. AB - The crystal structure of Cd5,Zn2-metallothionein from rat liver has been refined at 2.0 A resolution of a R-value of 0.176 for all observed data. The five Cd positions in the asymmetric unit of the crystal create a pseudo-centrosymmetric constellation about a crystallographic 2-fold axis. Consequently, the distribution of anomalous differences is almost ideally centrosymmetric. Therefore, the previously reported metal positions and the protein model derived therefrom are incorrect. Direct methods were applied to the protein amplitudes to locate the Cd positions. The new positions were used to calculate a new electron density map based on the Cd anomalous scattering and partial structure to model the metal clusters and the protein. Phases calculated from this model predict the positions of three sites in a (NH4)2WS4 derivative. Single isomorphous replacement phases calculated with these tungsten sites confirm the positions of the Cd sites from the new direct methods calculations. The refined metallothionein structure has a root-mean-square deviation of 0.016 A from ideality of bonds and normal stereochemistry of phi, phi and chi torsion angles. The metallothionein crystal structure is in agreement with the structures for the alpha and beta domains in solution derived by nuclear magnetic resonance methods. The overall chain folds and all metal to cysteine bonds are the same in the two structure determinations. The handedness of a short helix in the alpha-domain (residues 41 to 45) is the same in both structures. The crystal structure provides information concerning the metal cluster geometry and cysteine solvent accessibility and side-chain stereochemistry. Short cysteine peptide sequences repeated in the structure adopt restricted conformations which favor the formation of amide to sulfur hydrogen bonds. The crystal packing reveals intimate association of molecules about the diagonal 2-fold axes and trapped ions of crystallization (modeled as phosphate and sodium). Variation in the chemical and structural environments of the metal sites is in accord with data for metal exchange reactions in metallothioneins. PMID- 1942052 TI - X-ray analyses of aspartic proteinases. IV. Structure and refinement at 2.2 A resolution of bovine chymosin. AB - The structure of calf chymosin (EC 3.4.23.3), the aspartic proteinase from the gastric mucosa, was solved using the technique of molecular replacement. We describe the use of different search models based on distantly related fungal aspartic proteinases and investigate the effect of using only structurally conserved regions. The structure has been refined to a crystallographic R-factor of 17% at 2.2 A resolution with an estimated co-ordinate error of 0.21 A. In all, 136 water molecules have been located of which eight are internal. The structure of chymosin resembles that of pepsin and other aspartic proteinases. However, there is a considerable rearrangement of the active-site "flap" and, in particular, Tyr75 (pepsin numbering), which forms part of the specificity pockets S1 and S1'. This is probably a consequence of crystal packing. Electrostatic interactions on the edge of the substrate binding cleft appear to account for the restricted proteolysis of the natural substrate kappa-casein by chymosin. The local environment of invariant residues is examined, showing that structural constraints and side-chain hydrogen bonding can play an important role in the conservation of particular amino acids. PMID- 1942053 TI - Sequence-specific 1H n.m.r. assignments and determination of the three dimensional structure of reduced Escherichia coli glutaredoxin. AB - The determination of the nuclear magnetic resonance structure of reduced E. coli glutaredoxin in aqueous solution is described. Based on nearly complete, sequence specific resonance assignments, 813 nuclear Overhauser effect distance constraints and 191 dihedral angle constraints were employed as the input for the structure calculations, for which the distance geometry program DIANA was used followed by simulated annealing with the program X-PLOR. The molecular architecture of reduced glutaredoxin is made up of three helices and four stranded beta-sheet. The first strand of the beta-sheet (residues 2 to 7) runs parallel to the second strand (32 to 37) and antiparallel to the third strand (61 to 64), and the sheet is extended in an antiparallel fashion with a fourth strand (67 to 69). The first helix with residues 13 to 28 and the last helix (71 to 83) run parallel to each other on one side of the beta-sheet, with their direction opposite to that of the two parallel beta-strands, and the helix formed by residues 44 to 53 fills space available due to the twist of the beta-sheet and the reduced length of the last two beta-strands. The active site Cys11-Pro-Tyr Cys14 is located after the first beta-strand and occupies the latter part of the loop connecting this strand with the first helix. PMID- 1942054 TI - Structure of NADH peroxidase from Streptococcus faecalis 10C1 refined at 2.16 A resolution. AB - The crystal structure of NADH peroxidase (EC 1.11.1.1) from Streptococcus faecalis 10C1 (Enterococcus faecalis) has been refined to a resolution of 2.16 A using the simulated annealing method. The final crystallographic R-factor is 17.7% for all data in the resolution range 7 to 2.16 A. The standard deviations are 0.015 A in bond lengths and 3.0 degrees in bond angles for the final model, which includes all 447 amino acid residues, one FAD and 369 water molecules. The enzyme is a symmetrical tetramer with point group D2; the symmetry is crystallographic. The redox center of the enzyme consists of FAD and a cysteine (Cys42), which forms a sulfenic acid (Cys-SOH) in its oxidized state. A histidine (His10) close to Cys42 is likely to act as an active-site base. In the analyzed crystal, the enzyme was in a non-native oxidation state with Cys42 oxidized to a sulfonic acid Cys-SO3H. The chain fold of NADH peroxidase is similar to those of disulfide oxidoreductases. A comparison with glutathione reductase, a representative of this enzyme family, is given. PMID- 1942055 TI - Solution structure of human and mouse immunoglobulin M by synchrotron X-ray scattering and molecular graphics modelling. A possible mechanism for complement activation. AB - The pentameric 71-domain structure of human and mouse immunoglobulin M (IgM) was investigated by synchrotron X-ray solution scattering and molecular graphics modelling. The radii of gyration RG of human IgM Quaife and its Fc5, IgM-S, Fab'2 and Fab fragments were determined as 12.2 nm, 6.1 nm, 6.1 nm, 4.9 nm and 2.9 nm in that order. The RG values were similar for mouse IgM P8 and its Fab'2 and Fab fragments, despite the presence of an additional carbohydrate site. The IgM scattering curves, to a nominal resolution of 5 nm, were compared with molecular graphics models based on published crystallographic alpha-carbon co-ordinates for the Fab and Fc structures of IgG. Good curve fits for Fab were obtained based on the crystal structure of Fab from IgG. A good curve fit was obtained for Fab'2, if the two Fab arms were positioned close together at their contact with the C mu 2 domains. The addition of the Fc fragment close to the C mu 2 domains of this Fab'2 model, to give a planar structure, accounted for the scattering curve of IgM-S. The Fc5 fragment was best modelled by a ring of five Fc monomers, constrained by packing considerations and disulphide bridge formation. A position for the J chain between two C mu 4 domains rather than at the centre of Fc5 was preferred. The intact IgM structure was best modelled using a planar arrangement of these Fab'2 and Fc5 models, with the side-to-side displacement of the Fab'2 arms in the plane of the IgM structure. All these models were consistent with hydrodynamic simulations of sedimentation data. The solution structure of IgM can therefore be reproduced quantitatively in terms of crystallographic structures for the fragments of IgG. Putative Clq binding sites have been identified on the C mu 3 domain. These would become accessible for interaction with Clq when the Fab'2 arms move out of the plane of the Fc5 disc in IgM, that is, a steric mechanism exposing pre-existing Clq sites. Comparison with a solution structure for Clq by neutron scattering shows that two or more of the six globular Clq heads in the hexameric head-and-stalk structure are readily able to make contacts with the putative Clq sites in the C mu 3 domains of free IgM if if the Clq arm axis angle in solution is reduced from 40 degrees-45 degrees to 28 degrees. This could be the trigger for Cl activation. PMID- 1942056 TI - An efficient algorithm for identifying matches with errors in multiple long molecular sequences. AB - An efficient algorithm is described for finding matches, repeats and other word relations, allowing for errors, in large data sets of long molecular sequences. The algorithm entails hashing on fixed-size words in conjunction with the use of a linked list connecting all occurrences of the same word. The average memory and run time requirement both increase almost linearly with the total sequence length. Some results of the program's performance on a database of Escherichia coli DNA sequences are presented. PMID- 1942057 TI - Structure of the hirugen and hirulog 1 complexes of alpha-thrombin. AB - The isomorphous structures of the hirugen (N-acetylhirudin 53'-64' with sulfato Tyr63') and hirulog 1 (D-Phe-Pro-Arg-Pro-(Gly)4 desulfato-Tyr63'-hirugen) complexes of human alpha-thrombin have been determined and refined at 2.2 A resolution to crystallographic R-factors of 0.167 and 0.163, respectively. The binding of hirugen to thrombin is similar to that of the binding of the C terminal dodecapeptide of hirudin, including that of the terminal 3(10) helical turn. The sulfato Tyr63', which, as a result of sulfation, increases the binding affinity by an order of magnitude, is involved in an extended hydrogen bonding network utilizing all three sulfato oxygen atoms. The hirugen-thrombin complex is the first thrombin structure determined to have an unobstructed active site; this site is practically identical in positioning of catalytic residues and in its hydrogen bonding pattern with that of other serine proteinases. Hirulog 1, which is a poor thrombin substrate, is cleaved at the Arg3'-Pro4' bond in the crystal structure. The Arg3' of hirulog 1 occupies the specificity site, the D-Phe-Pro Arg tripeptide is positioned like that of D-Phe-Pro-Arg chloromethylketone in the active site and the Pro4'(Gly)4 spacer to hirugen is disordered in the structure, as is the 3(10) turn of hirugen. The latter must be related to the simultaneous absence both of sulfation and of the last residue of hirudin (Gln65'). In addition, the autolysis loop of thrombin (Lys145-Gly150) is disordered in both structures. Changes in circular dichroism upon hirugen binding are therefore most likely the result of the flexibility associated with this loop. PMID- 1942058 TI - Position effect on apparent helical propensities in the C-peptide helix. AB - A search has been made for position effects on apparent helix propensities when another amino acid is substituted for alanine in the C-peptide helix of ribonuclease A. Three internal alanine residues (Ala4, Ala5, Ala6) are used as sites for substitution. Five amino acids, Glu, His, Arg, Lys and Phe, are substituted singly in individual peptides at each of these three positions, and the pH profiles of helix content for the substituted peptides have been determined. The effect of using an acetyl or a succinyl amino-terminal-blocking group has also been determined for each substitution. A strong position effect is found at Ala5: the helix content of the substituted peptide is significantly higher for substitution at position 5 than at positions 4 or 6 in almost all cases. The reason for the position 5 effect is unknown. The results also show that electrostatic interactions often influence substitution experiments, and they provide data on the variability of substitution experiments made with a natural sequence peptide. PMID- 1942059 TI - Nuclear magnetic resonance structural studies of intramolecular purine.purine.pyrimidine DNA triplexes in solution. Base triple pairing alignments and strand direction. AB - Recently, P.A. Beal and P.B. Dervan, expanding on earlier observations by others, have established the formation of purine.purine.pyrimidine triple helices stabilized by G.GC, A.AT and T.AT base triples where the purine-rich third strand was positioned in the major groove of the Watson-Crick duplex and anti-parallel to its purine strand. The present nuclear magnetic resonance (n.m.r.) study characterizes the base triple pairing alignments and strand direction in a 31-mer deoxyoligonucleotide that intramolecularly folds to generate a 7-mer (R/Y )n.(R+)n(Y-)n triplex with the strands linked by two T5 loops and stabilized by potential T.AT and G.GC base triples. (R and Y stand for purine and pyrimidine, respectively, while the signs establish the strand direction.) This intramolecular triplex gives well-resolved exchangeable and non-exchangeable proton spectra with Li+ as counterion in aqueous solution. These studies establish that the T1 to C7 pyrimidine and the G8 to A14 purine strands are anti parallel to each other and align through Watson-Crick A.T and G.C pair formation. The T15 to G21 purine-rich third strand is positioned in the major groove of this duplex and pairs through Hoogsteen alignment with the purine strand to generate T.AT and G.GC triples. Several lines of evidence establish that the thymidine and guanosine bases in the T15 to G21 purine-rich third strand adopt anti glycosidic torsion angles under conditions where this strand is aligned anti-parallel to the G8 to A14 purine strand. We have also recorded imino proton n.m.r. spectra for an (R-)n.(R+)n(Y-)n triplex stabilized by G.GC and A.AT triples through intramolecular folding of a related 31-mer deoxyoligonucleotide with Li+ as counterion. The intramolecular purine.purine.pyrimidine triplexes containing unprotonated G.GC, A.AT and T.AT triples are stable at basic pH in contrast to pyrimidine.purine.pyrimidine triplexes containing protonated C+.GC and T.AT triples, which are only stable at acidic pH. PMID- 1942060 TI - Parallel and antiparallel Holliday junctions differ in structure and stability. AB - Two Holliday junction analogs, JA and JP, containing identical base-paired arms have been constructed from oligonucleotides. The former is constrained to adopt an antiparallel Sigal-Alberts structure, and the latter a parallel structure, by means of single strand d(T)9 tethers. We evaluate here the free energy difference between JA and JP using two different methods. One is a direct measurement of the ratio of the equilibrium constants for formation of branched structures from intact duplexes using one labeled strand and a competition assay. The second method estimates the difference in stability from the difference in thermal denaturation temperatures of JA and JP, using urea to shift the tm of the complexes. Both methods reveal a small free energy difference between the two complexes: JA is more stable than JP by -1.1(+/- 0.4) kcal (mol junction)-1, at 25 degrees C, 5 mM-Mg2+, from the first method, and by -1.6(+/- 0.3) kcal (mol junction)-1, according to the second. DNase I and the resolvase, endonuclease I from phage T7, cleave JA differently from JP in the vicinity of the branch, indicating that the structures of these two models differ at this site. Diethyl pyrocarbonate also reveals a difference in the major grooves. Comparison of the scission patterns of JA and JP by the reactive chemical probes methidium-propyl EDTA..Fe(II), [MPE.Fe(II)] and Cu(I)-[o-phenanthroline]2,[(OP)2Cu(I)], indicates that in both cases the branch point is a site of enhanced binding for drugs, as it is in the untethered four-arm junction containing the same core sequence at the branch. PMID- 1942061 TI - Influence of site-directed modifications on the formation of iron cores in ferritin. AB - The structure and crystal chemical properties of iron cores of reconstituted recombinant human ferritins and their site-directed variants have been studied by transmission electron microscopy and electron diffraction. The kinetics of Fe uptake have been compared spectrophotometrically. Recombinant L and H-chain ferritins, and recombinant H-chain variants incorporating modifications in the threefold (Asp131----His or Glu134----Ala) and fourfold (Leu169----Arg) channels, at the partially buried ferroxidase sites (Glu62,His65----Lys,Gly), a putative nucleation site on the inner surface (Glu61,Glu64,Glu67----Ala), and both the ferroxidase and nucleation sites (Glu62,His65----Lys,Gly and Glu61,Glu64,Glu67--- Ala), were investigated. An additional H-chain variant, incorporating substitution of the last ten C-terminal residues for those of the L-chain protein, was also studied. Most of the proteins assimilated iron to give discrete electron-dense cores of the Fe(III) hydrated oxide, ferrihydrite (Fe2O3.nH2O). No differences were observed for variants modified in the three- or fourfold channels compared with the unmodified H-chain ferritin. The recombinant L-chain ferritin and H-chain variant depleted of the ferroxidase site, however, showed markedly reduced uptake kinetics and comprised cores of increased diameter and regularity. Depletion of the inner surface Glu residues, whilst maintaining the ferroxidase site, resulted in a partially reduced rate of Fe uptake and iron cores of wider particle size distribution. Modification of both ferroxidase and inner surface Glu residues resulted in complete inhibition of iron uptake and deposition. No cores were observed by electron microscopy although negative staining showed that the protein shell was intact. The general requirement of an appropriate spatial charge density across the cavity surface rather than specific amino acid residues could explain how, in spite of an almost complete lack of identity between the amino acid sequences of bacterioferritin and mammalian ferritins, ferrihydrite is deposited within the cavity of both proteins under similar reconstitution conditions. PMID- 1942062 TI - Role of the disordered terminal regions of flagellin in filament formation and stability. AB - Terminal regions of flagellin from Salmonella typhimurium, residues 1 to 65 and 451 to 494, have no ordered tertiary structure in solution, which makes them very susceptible to proteolytic degradation. Flagellin was subjected to mild controlled proteolytic treatment with highly specific proteases to remove terminal segments from the disordered regions. It is demonstrated here that various fragments can be readily prepared that differ from each other in 1 x 10(3) to 2 x 10(3) Mr segments in their NH2- or COOH-terminal regions. Terminally deleted fragments of flagellin were used to clarify the role of the disordered regions in the self-assembly of flagellin. The polymerization ability of the fragments was tested by inducing filament formation with ammonium sulfate. We found that fragments of flagellin containing large terminal deletions could form straight filaments, although the stability of these filaments required high salt concentrations. Even a fragment lacking the whole mobile COOH-terminal part of flagellin and 36 residues from the NH2-terminal region could form long filaments. The fragments could be also polymerized onto native flagellar seeds, suggesting that the subunit packing of the filaments of fragments is similar to that of the native ones. The fragments could also copolymerize with native flagellin, resulting in various helical forms. Filaments of fragments were found to be straight at both pH 4.0 and pH 12.5, indicating that they might have lost their polymorphic ability. Our results show that the major part of the disordered terminal regions of flagellin is not essential for polymerization, but it does play an important role in stabilization of the filaments and in influencing their polymorphic conformation. PMID- 1942063 TI - Characterization and preliminary attempts for derivatization of crystals of large ribosomal subunits from Haloarcula marismortui diffracting to 3 A resolution. AB - An improved form of crystals of large (50 S) ribosomal subunits from Haloarcula marismortui, formally named Halobacterium marismortui, diffracting to 3 A resolution, has been obtained by the addition of 1 mM-Cd2+ to the crystallization medium, which contained more than 1.9 M of other salts. The improved crystals, grown from functionally active particles to an average size of 0.3 mm x 0.3 mm x 0.08 mm, are isomorphous with the previously reported ones, which diffracted to 4.5 A. They are of space group C222(1), cell dimensions a = 210 A, b = 300 A, c = 581 A, and contain one particle in the asymmetric unit. Their superior internal order is reflected not only in their high resolution, but also in their reasonable mosaicity (less than 0.3 degrees). In contrast to the previously grown crystals, the new ones are of adequate mechanical strength and survive well the shock-cooling treatment. Due to their weak diffracting power, all crystallographic studies have been performed with synchrotron radiation. At cryotemperature, these crystals showed no measurable decay for a few days of irradiation and a complete diffraction data set could be collected from a single crystal. Efforts for initial phasing by specific and quantitative derivatization with super-dense heavy-atom clusters are in progress. PMID- 1942064 TI - Characterization of crystals of an intact monoclonal antibody for canine lymphoma. AB - A monoclonal antibody of the subclass IgG2a specific for canine lymphoma cells has been crystallized by vapor diffusion from polyethylene glycol 8000. the crystals, which occasionally measure nearly a millimeter on edge, have been examined by X-ray diffraction. The crystals are of triclinic space group P1 with unit cell parameters of a = 66.39 A, b = 77.34 A, c = 101.42 A, alpha = 87.60 degrees, beta = 92.55 degrees, gamma = 97.54 degrees and cell volume of V = 4.84 x 10(5) A3. There is one entire antibody molecule as the asymmetric unit of the crystals. Three-dimensional X-ray diffraction data have been collected to 2.8 A resolution and a self rotation function calculation shows a pronounced peak indicating at least an approximate non-crystallographic dyad axis. PMID- 1942065 TI - Preliminary investigation of crystals of the neutral lipase from Pseudomonas fluorescens. AB - The neutral lipase from the bacteria Pseudomonas fluorescens, marketed under the trade name LpL-200S, has been crystallized in a form suitable for X-ray diffraction analysis from 35% n-propanol at pH 8.5. The crystals are monoclinic prisms and are of space group C2 with a = 91.00 A, b = 47.17 A, c = 35.21 A and beta = 121.43 degrees. There is one molecule of the protein as the asymmetric unit of the crystals. The diffraction pattern extends to at least 1.6 A resolution and the crystals are extremely robust in terms of X-ray exposure. PMID- 1942066 TI - Crystals of a bovine neurophysin II tripeptide complex. AB - A bovine neurophysin II S-methyl-Cys-Tyr-Phe-NH2 complex has been crystallized using ammonium sulfate as the precipitating agent. The crystals are orthorhombic, the space group is either I222 or I2(1)2(1)2(1) with a = 124.9 A, b = 69.6 A and c = 151.5 A. The crystals diffract to at least 3.0 A resolution. Based on one neurophysin tetramer per asymmetric unit, the Matthews coefficient is calculated to be 3.92 with a solvent content of 69%. PMID- 1942067 TI - NFY or a related CCAAT binding factor can be replaced by other transcriptional activators for co-operation with HNF1 in driving the rat albumin promoter in vivo. AB - Like many eukaryotic genes, the rat albumin promoter contains a CCAAT consensus motif at position -80. In transfected H4II hepatoma cells the strength of this promoter depends to a large extent on the integrity of a hepatic nuclear factor 1 (HNF1) binding site located at position -60 and to a lesser extent on the CCAAT element. However, if the affinity for HNF1 is reduced, the CCAAT-box becomes essential for high, and tissue specific, promoter activity. We wished to determine which, among the different CCAAT binding factors co-existing in eukaryotic cells, was responsible for this co-operativity with HNF1. To this end we prepared a series of mutants of the CCAAT sequence and compared their effects on albumin promoter activity in vivo and on the binding of different CCAAT binding factors in vitro. Our results strongly suggest that a ubiquitous factor NFY (also designated CBF, ACF, CP1) interacts with this CCAAT element in vivo. We propose that during development NFY could facilitate transcription of the albumin gene in hepatocytes when the concentration of HNF1 is limiting. This co operativity in transcriptional activation is not due to strict co-operativity in DNA binding between the two proteins and is not limited to NFY or a closely related factor, as the CCAAT-box can be replaced by AP1, SP1 or E2 target sites without significantly affecting the final activity. PMID- 1942068 TI - Conserved chromatin structure in c-myc 5'flanking DNA after viral transduction. AB - The role of local sequence information in establishing the chromatin structure of the human c-myc upstream region (MUR) was investigated. Adeno-associated virus (AAV)-mediated gene transduction was used to introduce an additional unrearranged copy of the 2.4 kb HindIII-XhoI fragment of the MUR into a novel location in the genome in each of two cloned HeLa cell lines. The AAV-based rep- cap- viral vector SKMA used to transduce the MUR retained only 1.4 kb (24%) of the AAV genome and could accommodate inserts as large as 2.4 kb. SKMA was capable of infecting HeLa cells and integrating into the host genome at single copy number. Integration may have occurred at a preferred site in the HeLa genome, but this site was apparently distinct from the previously identified preferred AAV integration site on human chromosome 19. Indirect end-labelling was used to map DNase I and micrococcal nuclease (MNase) cleavage sites over the transduced c-myc sequences and the endogenous c-myc loci in infected HeLa cells. A similarly ordered chromatin domain, extending 5' from c-myc promoter P0, was found to exist at the transduced c-myc locus in each clone. The position and relative sensitivity of 13 MNase cleavage sites and five DNase I hypersensitive sites, originally identified at the endogenous MUR in non-transduced cells, were shown to be conserved when this DNA was moved to a new chromosome site. A conserved DNase I hypersensitive site also was mapped to the region between the left AAV terminal repeat and AAV promoter P5. These results suggest that the information required to establish the particular chromatin structure of the MUR resides within the local DNA sequence of that region. PMID- 1942069 TI - Systematic mutation of bacteriophage T4 lysozyme. AB - Amber mutations were introduced into every codon (except the initiating AUG) of the bacteriophage T4 lysozyme gene. The amber alleles were introduced into a bacteriophage P22 hybrid, called P22 e416, in which the normal P22 lysozyme gene is replaced by its T4 homologue, and which consequently depends upon T4 lysozyme for its ability to form a plaque. The resulting amber mutants were tested for plaque formation on amber suppressor strains of Salmonella typhimurium. Experiments with other hybrid phages engineered to produce different amounts of wild-type T4 lysozyme have shown that, to score as deleterious, a mutation must reduce lysozyme activity to less than 3% of that produced by wild-type P22 e416. Plating the collection of amber mutants covering 163 of the 164 codons of T4 lysozyme, on 13 suppressor strains that each insert a different amino acid substitutions at every position in the protein (except the first). Of the resulting 2015 single amino acid substitutions in T4 lysozyme, 328 were found to be sufficiently deleterious to inhibit plaque formation. More than half (55%) of the positions in the protein tolerated all substitutions examined. Among (N terminal) amber fragments, only those of 161 or more residues are active. The effects of many of the deleterious substitutions are interpretable in light of the known structure of T4 lysozyme. Residues in the molecule that are refractory to replacements generally have solvent-inaccessible side-chains; the catalytic Glu11 and Asp20 residues are notable exceptions. Especially sensitive sites include residues involved in buried salt bridges near the catalytic site (Asp10, Arg145 and Arg148) and a few others that may have critical structural roles (Gly30, Trp138 and Tyr161). PMID- 1942070 TI - Fibrinogen structure in projection at 18 A resolution. Electron density by co ordinated cryo-electron microscopy and X-ray crystallography. AB - Electron microscope images of frozen-hydrated crystals of a proteolytically modified fibrinogen show excellent preservation of the structure. An electron density map of the key centric projection of the crystal at 18 A resolution has been obtained by combining the phases derived from cryo-electron microscopy with X-ray amplitudes. Simulation methods developed in earlier studies have been used to interpret the map. In contrast to the earlier images, the map allows us to visualize the coiled-coil region of the molecule and possible substructure in the beta domains. The map also shows that there is a marked difference in density in the two regions corresponding to the molecular ends where the gamma domains interact. A possible interpretation of this finding is provided by assuming substructure in the gamma domains and the breaking of molecular symmetry where these domains interact. Some additional constraints useful for the determination of the three-dimensional structure were obtained from cryo-electron micrographs of a perpendicular view at 25 A resolution. Implications of this working model for the molecular length and contacts in the filaments in both the crystal and fibrin are described. The data used here will be valuable as a starting point for obtaining the three-dimensional structure. PMID- 1942071 TI - Amino acid substrate specificity of Escherichia coli phenylalanyl-tRNA synthetase altered by distinct mutations. AB - Neither the tertiary structure nor the location of active sites are known for phenylalanyl-tRNA synthetase (PheRS; alpha 2 beta 2 structure), a member of class II aminoacyl-tRNA synthetases. In an attempt to detect the phenylalanine (Phe) binding site, two Escherichia coli PheRS mutant strains (pheS), which were resistant to p-fluorophenylalanine (p-F-Phe) were analysed genetically. The pheS mutations were found to cause Ala294 to Ser294 exchanges in the alpha subunits from both independent strains. This alteration (S294) resided in the well conserved C-terminal part of the alpha subunit, precisely within motif 3, a typical class II tRNA synthetase sequence. We thus propose that motif 3 participates in the formation of the Phe binding site of PheRS. Mutation S294 was also the key for proposing a mechanism by which the substrate analogue p-F-Phe is excluded from the enzymatic reaction; this may be achieved by steric interactions between the para-position of the aromatic ring and the amino acid residue at position 294. The Phe binding site model was then tested by replacing the alanine at position 294 as well as the two flanking phenylalanines (positions 293 and 295) by a number of selected other amino acids. In vivo and in vitro results demonstrated that Phe293 and Phe295 are not directly involved in substrate binding, but replacements of those residues affected PheRS stability. However, exchanges at position 294 altered the binding of Phe, and certain mutants showed pronounced changes in specificity towards Phe analogues. Of particular interest was the Gly294 PheRS in which presumably an enlarged cavity for the para position of the aromatic ring allowed an increased aminoacylation of tRNA with p-F-Phe. Moreover, the larger para-chloro and para-bromo derivatives of Phe could interact with this enzyme in vitro and became highly toxic in vivo. The possible exploitation of the Gly294 mutant PheRS for the incorporation of non proteinogenic amino acids into proteins is discussed. PMID- 1942072 TI - Three-dimensional architecture of identified cerebral neurosecretory cells in an insect. AB - The organization of identified neurosecretory cell groups in the larval brain of the tobacco hornworm, Manduca sexta, was investigated immunocytologically. Computer-assisted three-dimensional reconstruction was used to examine the architecture of the neurosecretory cell groups. The group III lateral neurosecretory cells (L-NSC-III) which produce the prothoracicotropic hormone are located dorsolaterally in the protocerebrum and extend axons medially that decussate to the contralateral lobe prior to exiting the brain through the nervi corporis cardiaci I + II. The group IIa2 medial neurosecretory cells (M-NSC IIa2) are located anteriorly in the medial dorsal protocerebrum. The axons of these cells also exit the brain via the contralateral nervi corporis cardiaci I + II. However, their axons traverse a different pathway through the brain from that of the L-NSC III axons. Each of the cell groups possesses elaborate dendrites with terminal varicosities. The dendrites can be classified into specific fields based upon their location and projection pattern within the brain. The dendrites for these two neurosecretory cell groups overlap in specific regions of the protocerebral neuropil. After the axons of these neurosecretory cells exit the brain through the retrocerebral nerve, they innervate the corpus allatum where they arborize to form neurohemal terminals in strikingly different patterns. The L-NSC III penetrate throughout the glandular structure and the M-NSC IIa2 terminals are restricted to the external sheath. A third group of cerebral neurosecretory cells, the ventromedial neurons (VM) which stain with the monoclonal antibody to prothoracicotropic hormone in Manduca, are located anteriorly in the medial region of the brain. The axons of these cells do not exit the brain to the retrocerebral complex, but rather pass through the circumesophageal connectives and ventral nerve cord. These neurons appear to be the same VM neurons that produce eclosion hormone. One dendritic field of the L NSC III terminates in close apposition to the VM neurons. The distinct morphologies of these neurosecretory cell groups in relation to other cell groups and the distribution of neuropeptides within the neurons suggest that insect neurosecretory cells, like their vertebrate counterparts, may have multiple regulatory roles. PMID- 1942073 TI - Structure and sympathetic innervation of the intracranial arteries in the giraffe (Giraffa camelopardalis). AB - Fluorescence histochemistry discloses that the carotid rete mirabile in the giraffe has a poor sympathetic innervation. In contrast, the efferent artery of the rete (internal carotid artery) and the cerebral arteries show moderate sympathetic innervation. A certain degree of regional variability was noted in which the rostral arteries (anterior and middle cerebral) receive more sympathetic nerves than the caudal (posterior communicating and basilar) arteries. The sympathetic nerves on the giraffe cerebral vessels may constitute part of a host of mechanisms by which regional blood flow to the brain is regulated. Conversely, the paucity of sympathetic innervation of the carotid rete mirabile may indicate that this structure does not play an active role in vasoconstrictor responses during postural changes of the head. PMID- 1942074 TI - Magnetic resonance imaging study of the structure of the yolk in the developing avian egg. AB - Magnetic resonance imaging (MRI) techniques were used to study the morphology of the latebra and concentric rings seen in the yolk of White Leghorn eggs during development of the avian embryo. Previous studies of the macroscopic structure of avian yolk have revealed the latebra, a vase-shaped structure beneath the blastoderm composed of white yolk. The bulbous portion in the center of the yolk is termed the body of the latebra. The thinner portion extending toward the blastoderm is referred to as the neck of the latebra. As the neck of the latebra approaches the blastoderm, it flares out to become the nucleus of Pander. The remainder of the yolk often features alternating concentric layers of white and yellow yolk. These layers, which appear as rings in sections, are thought to represent the daily accumulation of yolk during oogenesis. In this study eggs were imaged with a single slice spin echo sequence using MRI parameters that maximized the visualization of the latebra and concentric rings in the egg yolk. Some experiments were conducted for 2 to 3 day periods with eggs kept in the bore of the magnet using a small incubator that was constructed using a temperature controlled water pump. The concentric rings of the yolk and the body of the latebra flatten and become more elliptical during development. The neck of the latebra becomes shorter and disappears around the 7th day of incubation. The body of the latebra starts to become incorporated into the embryo at about the 7th day of incubation and usually disappears by the 13th day. The concentric rings are no longer visible as distinct entities at this time. Histochemical procedures carried out as a result of MRI findings indicate that the latebra is an iron-rich structure. PMID- 1942075 TI - Reduction of biological effluents in purge and trap micro reaction vessels and detection of endothelium-derived nitric oxide (edno) by chemiluminescence. AB - Various analytical approaches have been used to measure endothelium-derived nitric oxide (NO). We have detected NO in perfusates with a sample size as low as 2 ml after acidification with 4 N HC1 to pH less than 2 at 25 degrees C by using a Nitric Oxide Analyser (Sievers, Colorado). This procedure had the advantage that the detectable level of NO was enhanced by the self-decomposition of HNO2 when the PH less than pKa of NHO2 (pKa = 3.15) and also the reaction temperature of 25 degrees C substantially increased the half-line of NO. Palmer, et al., measured NO released by cultured porcine endothelial cells by chemiluminescence after passing cell effluents continuously at a rate of 5 ml/min into 75 ml of 1% sodium iodide in glacial acetic acid. The larger volumes involved in this method for continuous refluxing, made it less desirable for the detection of endothelium derived nitric oxide. Feelisch et al. utilized the activation of soluble guanylate cyclase, as well as, the quantitative oxidation of oxyhemoglobin to methemoglobin in aqueous solutions by NO as a means of measuring nitric oxide. We describe here a modification of our earlier micromethod which now enables us to detect NO after complete reduction with glacial acetic acid and sodium iodide. A comparison of the two procedures indicate that while freshly prepared NO standard solutions gave identical chemiluminescence response with and without reduction, effluents from bovine intrapulmonary artery under basal conditions gave substantially higher values upon reduction. PMID- 1942076 TI - The interdependence of paradigmatic shifts and normal science: three examples in the field of cardiovascular science. PMID- 1942077 TI - What is a paradigm and when does it shift? PMID- 1942078 TI - Decreased 1,2-diacylglycerol levels in myopathic hamster hearts during the development of heart failure. AB - 1,2-Diacylglycerol is believed to play an important role in cellular functions through protein kinase C activation, although its role in cardiac functions remains largely unexplored. We determined the level of 1,2-diacylglycerol and its fatty acid composition in heart tissues from Syrian hamsters with hereditary cardiomyopathy (BIO 14.6 strain) during the development of congestive heart failure from 90 days to 240 days of age. The myopathic hamsters had lower contents of triglyceride and of the major phospholipids, phosphatidylcholine, phosphatidylethanolamine and cardiolipin, in the myocardium when compared to normal hamsters, whereas there was no difference in the cholesterol content. No difference in the myocardial 1,2-diacylglycerol content was observed at 90 days of age. On the other hand, 1,2-diacylglycerol contents in myopathic hearts at 160 and 240 days of age were significantly lower by 21% and 52%, respectively, then in age-matched normal hamsters. The oldest hamsters (240-day-old) showed reduced 1,2-diacylglycerol levels in both groups despite an age-related increase in most lipids. The 1,2-diacylglycerol fatty acid composition profile was found to be different from that of other lipids, and there were several differences in the fatty acid composition of 1,2-diacylglycerol between the two groups at 240 days of age. These results indicate that decreased levels of 1,2-diacylglycerol occur concomitantly with congestive heart failure in the myopathic hamsters. PMID- 1942079 TI - Contractile, metabolic and electrophysiologic effects of ethanol in the isolated rat heart. AB - The metabolic, functional and electrical effects of ethanol were studied in the isolated isovolumic rat heart retrogradely perfused at constant flow using phosphorus-31 nuclear magnetic resonance spectroscopy and surface electrogram recordings. Ethanol (0.75 to 6.0 vol%; 128 to 1024 mM) caused a concentration dependent decline in developed pressure without a change in adenosine triphosphate, phosphocreatine, inorganic phosphate or pH. Ethanol (6%) caused abolition of electrical activity. The functional decline could be rapidly and completely reversed by perfusing with ethanol-free solution and, significantly although not completely, reversed by increasing perfusate calcium to 4 mM. Furthermore, ethanol shifted the perfusate calcium-tetanic pressure relationship in the presence of ryanodine (1 microM) downwards and to the right. The results suggest ethanol's acute effects in this model are not mediated by changes in energy metabolism or cellular pH, but rather by sarcolemmal effects and by a decrease in both myofilament calcium sensitivity and maximal force generating ability. PMID- 1942080 TI - Immunodetectable levels of the inhibitory guanine nucleotide-binding regulatory proteins in failing human heart: discordance with measurements of adenylate cyclase activity and levels of pertussis toxin substrate. AB - Human hearts with idiopathic dilated cardiomyopathy have diminished adenylate cyclase activity and increased amounts of the alpha-subunit of the inhibitory guanine nucleotide-binding regulatory protein (alpha Gi) as measured by pertussis toxin catalyzed ADP-ribosylation. We utilized specific antisera against synthetic peptides corresponding to amino sequences deduced from cDNA's encoding the three alpha Gi subspecies to compare the immunologic and bioactivity levels of Gi in failing and non-failing human hearts. The various antisera detected three peptides with Mr 42,000, 38,000, and 37,000. Only the Mr 42,000 peptide co migrated with the pertussis toxin substrate. Although functional activity of alpha Gi was increased in the particulate fractions of the failing heart as measured by inhibition of guanine nucleotide-stimulated adenylate cyclase activity and the quantity of pertussis toxin substrate was also increased, there were not associated changes in the levels of immunodetectable Gi. Therefore, the increased functional activity of Gi in the failing human heart as assessed by adenylate cyclase measurements cannot be explained by a relative increase in the among of Gi protein. PMID- 1942081 TI - Effect of aspirin on local prostaglandin production and serotonin accumulation in a canine model with coronary cyclic flow variations or thrombosis. AB - We have reported that thromboxane A2 and serotonin are two important mediators of coronary cyclic flow variations (CFVs) caused by recurrent platelet aggregation and dislodgement on a stenosed coronary arterial wall with endothelial injury. To test the hypothesis that blocking the synthesis of thromboxane A2 would not prevent serotonin release, 1.1, 4.6, and 9.2 mg/kg of aspirin were administered through the left atrium to 27 dogs with CFVs. The CFV elimination rate was 70% in the aspirin-treated dogs. Thromboxane B2 and serotonin concentrations were measured in different coronary arterial segments. There were significantly lower thromboxane B2 and 6-keto-PFG1a levels in the stenosed left arterior descending (LAD) segments with increasing dosage of aspirin-208 +/- 36, 24 +/- 31, 50 +/- 6 ng/g (P less than 0.0001) and 125 +/- 27, 58 +/- 38, 25 +/- 5 ng/g (P less than 0.0001), respectively. Serotonin levels were significantly higher in stenosed LAD (265.7 +/- 131.2 ng/g) than in LAD segments proximal or distal to the stenosis and in corresponding circumflex coronary artery segments, 17.1 +/- 3.7, 18.6 +/- 3.7, and 19.2 +/- 5.1 ng/g, respectively (P less than 0.05) following the highest dose of aspirin. In 41 additional dogs, electrical injury was used to initiate thrombosis in the circumflex artery and in those receiving aspirin (15 mg/kg) (n = 5), occlusive thrombus formation was inhibited. However, the local accumulation of serotonin was not significantly different between the control (194 +/- 27 ng/g) (n = 36) and the aspirin-treated group (167 +/- 19 ng/g) (n = 5). In vitro platelet aggregation induced by arachidonic acid was inhibited by the in vivo administration of 1.1 mg/kg of aspirin and abolished by 4.6 + 1.1 and 9.2 + 4.6 + 1.1 mg/kg of aspirin. However, serotonin-induced platelet aggregation was not affected following all doses of aspirin. Thus, aspirin eliminates CFVs in 70% of dogs, and markedly diminishes thromboxane A2 and prostacyclin concentrations in stenosed canine coronary arteries, but it does not prevent local serotonin accumulation. Similarly, aspirin prevents occlusive coronary thrombosis in dogs with electrically-induced endothelial injury, but it did not prevent local assumulation of serotonin. These experimental findings suggest that cyclo oxygenese inhibition does not prevent serotonin accumulation at sites of coronary artery endothelial injury, and they thereby help provide a potential explanation of the lack of complete protection provided by aspirin in eliminating CFVs in this experimental model. PMID- 1942082 TI - Electromechanical effects of angiotensin in human atrial tissues. AB - Effects of exogenous angiotensin I (AI) and angiotensin II (AII) on action potential and contractile force of isolated atrial trabeculae obtained at cardiac surgery were studied by means of a standard microelectrode technique. In trabeculae driven electrically at a cycle length of 1 s, AII (8.4 nM - 8.4 microM) increased the contractile force with a peak effect occurred near 0.84 microM. The inotropic effect of AII was markedly inhibited by 1 microM saralasin or 1 microM diltiazem. AI (0.65 nM - 6.5 microM) also induced positive inotropic effect in a concentration-dependent manner. This inotropic effect was decreased significantly after 3 microM captopril pretreatment. In trabeculae active spontaneously in normal Tyrode solution, AI and AII increased significantly rate of diastolic depolarization and spontaneous discharges as well as force of contraction. These chronotropic effects were inhibited by captopril and saralasin, respectively. Captopril (0.3 nM - 3 microM) or saralasin (0.001 - 1 microM) alone also induced dose-dependent negative chronotropic effects. The present findings suggest the existence of functional AII receptors in human atrial tissues. The stimulatory effects of angiotensin appear to be related to an increase in cellular calcium. PMID- 1942083 TI - Cardiac adenosine production is linked to myocardial pO2. AB - Experiments were performed on isolated perfused guinea-pig hearts (n = 45) to further evaluate the stimulus that triggers cardiac adenosine production. Stimulation of hearts with isoproterenol (4 nM, 20 min) enhanced left ventricular dP/dtmax, heart rate and myocardial oxygen consumption within 1 min to new steady state values, whereas coronary venous adenosine concentration only transiently increased reaching its maximum between 1 and 3 min of stimulation. Rate of accumulation of S-adenosylhomocysteine (SAH), a measure of the free cytosolic adenosine concentration, was steepest immediately following onset of stimulation and then progressively declined. Similar to adenosine, changes in coronary venous pO2 were phasic and adenosine release and pO2 closely correlated. Norepinephrine (20 nM) which increased myocardial oxygen consumption to a comparable extent as isoproterenol (4 nM) further decreased coronary venous pO2 and increased coronary venous adenosine. When myocardial oxygen supply was systematically varied by changing coronary perfusion pressure from 60 to 90 and 35 cmH2O, respectively, the adenosine release during isoproterenol (2 nM) was markedly enhanced at 35 cmH2O but blunted at 90 cmH2O. Similarly SAH accumulation was greatest at 35 cmH2O and smallest at 90 cmH2O. It is concluded that changing myocardial oxygen consumption is not a sufficient cause to enhance adenosine formation. Myocardial oxygenation as reflected by changes in coronary venous pO2 closely correlates with changes in free cardiac adenosine as evidenced by two independent indices: tissues SAH and coronary venous adenosine concentration. The stimulus triggering cardiac adenosine formation is most likely the imbalance of oxygen supply and oxygen demand. PMID- 1942084 TI - Transient outward currents and action potential alterations in rabbit ventricular myocytes. AB - To clarify ionic mechanisms underlying successive changes in action potential repolarization upon sudden increase in driving rate or initiation of rapid drive after a rest, membrane potentials and currents were recorded from isolated rabbit ventricular myocytes using the suction-pipette whole-cell clamp method. When 20 action potentials were elicited with a stimulus frequency of 2.0 Hz after a rest period of 20 s, the plateau and action potential duration showed complex changes in successive beats, whereas they were nearly constant with stimulation at 0.1 Hz. There were only weak correlations between changes in action potential parameters and preceding diastolic intervals. The changes were prominent in the first 10 beats but subsided gradually thereafter, attaining nearly steady configurations of action potentials. When depolarizing pulses were applied at a fast rate, under the voltage clamp, the amplitudes of the initial inward current in the presence of tetrodotoxin changed greatly depending on the pulse numbers and diastolic intervals, whereas the delayed outward K+ current changed little. Variations of the initial inward current in successive pulses were caused by different degrees of activation and recovery from inactivation in the Ca2+ current, the Ca(2+)-sensitive and -insensitive transient outward current. While inhibition of either one or two current components decreased the action potential alterations, blocking the three components completely abolished them. These results indicate that alterations of the Ca(2+)-sensitive and -insensitive transient outward current together with the Ca2+ current contribute to the action potential alterations after initiation of rapid drive or an increase in driving rates. PMID- 1942085 TI - Aortic glutathione-related antioxidant defences in rabbits subjected to suprarenal aortic coarctation hypertension. AB - In seven rabbits subjected to suprarenal aortic coarctation hypertension, the segments above and below the coarctation were tested for the antioxidant defences (i.e. acid-soluble thiol compounds, selenium-dependent and selenium-independent glutathione peroxidase, glutathione reductase, glutathione transferase) and thiobarbituric acid-reactive substances. Seven sham-operated rabbits served as controls. Systolic blood pressure proximal to the ligature increased significantly with respect to pre-operative values after 16 days (117 +/- 8.3 vs 71.7 +/- 5.2 mmHg, P less than 0.05), while pressure distal to the ligature remained normotensive. Higher values of acid-soluble thiol compounds, thiobarbituric acid-reactive substances and increased activities of selenium dependent glutathione peroxidase, glutathione reductase and glutathione transferase were assayed in the suprarenal with respect to the subrenal segment in both groups. However, the values of the upper segments were more elevated in the experimental group than in controls, but no differences were observed in the lower segments. Glutathione peroxidase activity assayed with cumene hydroperoxide was higher than the activity assayed with hydrogen peroxide in the hypertensive segments, but no differences were detected in the substenotic and control segments. Furthermore, an isoenzymatic form of glutathione transferase, analogous to rat 8-8 glutathione transferase isoenzyme, was detected by immunodiffusion in the hypertensive aorta. The following conclusions may be drawn: (1) a biochemical gradient in glutathione-related enzymes, acid-soluble thiol compounds and thiobarbituric acid-reactive substances between the proximal and distal aorta seems to exist in control rabbits; (2) suprarenal aortic coarctation induces a significant increase in glutathione-related antioxidant defences and thiobarbituric acid-reactive substances of the hypertensive aortic wall. PMID- 1942086 TI - Transsarcolemmal sodium-calcium exchange and myocardial oxygen consumption in isolated rat ventricular myocytes. AB - We studied oxygen consumption and energy metabolism in isolated rat ventricular myocytes which were subjected to an abrupt change in the cation composition of the extracellular medium ('transition'); extracellular [Na+] was decreased either alone or in combination with a change of [K+] or [Ca2+]. The magnitude of change of the cation concentration(s) was varied. The respiratory rate (vO2) of myocytes changed biphasically after such a transition. vO2 increases to a maximum after about 25 to 30 s and returns to almost control after 180 to 200 s. vO2-max depends on both the nature of the cation(s) of which the concentration(s) are varied and on the magnitude of these change(s); vO2-max can almost be as high as that induced by uncoupling of oxidative phosphorylation with DNP. The free energy of hydrolysis of cytoplasmic ATP hardly decreases after transition. Cell viability remains unaltered, although an increasingly larger fraction of rod shaped cells transform to a hypercontracted state with increasing magnitude of the extracellular ion concentration change. Reversal of the ionic change or addition of EGTA at 30 s after transition accelerates the return of vO2 to the value prior to transition. In the presence of ouabain, vO2-max is higher and return to control is slower and incomplete. The total amount of oxygen consumption after transition, is linearly related to the initial change of the free energy of the Na+/Ca(2+)-exchanger caused by the cation concentration change(s); this relationship does not depend on the nature of the cation(s) changed. We conclude that the transient increase of vO2 after transition is regulated by intracellular free [Ca2+], which transiently increases. This transient increase is caused by change of the thermodynamic driving force on the Na+/Ca(2+)-exchanger after transition. PMID- 1942087 TI - What constitutes the calcium paradox? PMID- 1942088 TI - The intracellular Na+ concentration prior to Ca2+ repletion has no bearing on the occurrence of the calcium paradox as originally defined. PMID- 1942089 TI - The calcium paradox: a role for [Na]i, a cellular or tissue basis, a property unique to the Langendorff perfused heart? A bundle of contradictions! PMID- 1942090 TI - Adenosine receptor blockade enhances isoproterenol-induced increases in cardiac interstitial adenosine. AB - The failure of adenosine receptor antagonists to consistently attenuate metabolic coronary vasodilation suggests that adenosine is not a primary regulator of functional hyperemia. An alternative hypothesis, however, is that metabolic stimulation of the heart in the presence of an adenosine receptor antagonist results in enhanced interstitial levels of adenosine which then might overcome the blockade. To test this hypothesis, interstitial levels of adenosine and inosine were estimated by HPLC analysis of fluid which exudes from the epicardial surface of isolated rat hearts perfused with crystalloid solution at constant flow. Isoproterenol infusion (10 nM) produced increases in heart rate, left ventricular systolic pressure, rate of pressure development, myocardial oxygen consumption and adenosine and inosine concentrations of venous effluent and surface exudate and produced decreases in coronary vascular resistance. The presence of the adenosine receptor antagonist, 8-(4-sulfophenyl) theophylline (spT) (100 microM), in the perfusate had little or no effect upon most of the responses to isoproterenol except that it significantly enhanced the isoproterenol-induced increases in adenosine release and adenosine concentrations in the venous effluent and surface exudate. The isoproterenol-induced change in adenosine concentration per unit change in oxygen consumption was approximately 3 fold greater in the presence of spT than in its absence. This extra adenosine production may tend to overcome the competitive blocking effect of spT and help explain why agents such as spT are not always effective in blocking metabolic vasodilation. PMID- 1942091 TI - Alterations in electrical and contractile behavior of isolated cardiomyocytes by hydrogen peroxide: possible ionic mechanisms. AB - The development of H2O2-induced changes in membrane potentials, membrane currents and corresponding contractile activity (shortening) were studied in rat and guinea-pig ventricular myocytes using the suction-pipette whole-cell clamp method. The cells exhibited a different sensitivity to 30 microM H2O2 in terms of time development of the changes, which were fully irreversible. The observed changes are described in three phases: (1) prolongation of action potential duration (APD) accompanied by increased contractility. With a prolonged exposure, the increased APD was accompanied by early afterdepolarizations (EADs), delayed afterdepolarizations (DADs) and aftercontractions. The changes in APD and the EADs were fully and permanently abolished by tetrodotoxin (TTX) but not by nifedipine, while the DADs and aftercontractions were abolished by ryanodine. These changes preceded phase (2), which was characterized by APD shortening, a decrease in contractility, membrane depolarization, single or multiple extrasystoles, or steady spontaneous activity; this phase could not be prevented by any of the above pharmacological interventions and resulted in a final phase (3) characterized by full depolarization and inexcitability. All the above changes were prevented by intracellular application of iron chelator deferoxamine, indicating that .OH generated intracellularly in the presence of Fe3+ induces the observed changes. The examination of membrane currents indicated that the increased APD may be due to an increase in the TTX-sensitive Na+ current as well as to the decreased delayed current, while L-type Ca2+ channels appear to be unaffected. The shortening of APD during the second phase was associated with a large increase in the delayed K+ current. The increased contractility in the first stage appears to be due to increased sarcolemmal Ca2+ influx via Na(+)-Ca2+ exchange (among other possible mechanisms), leading to a loading of sarcoplasmic reticulum that eventually results in Ca2+ overload and functional failure. PMID- 1942092 TI - Hypoxia-induced change in prostanoids production and coronary flow in isolated rat heart. AB - The contribution of prostanoids to the change in coronary flow induced by hypoxia was examined in Langendorff-perfused rat heart. In the coronary effluent, 5 prostanoids, i.e., prostaglandins (PGs) D2, E2, and F2 alpha, 6-keto PGF1 alpha and thromboxane (TX) B2, were quantified by GC/MS, whereas PGA2, B2, and E1 were not detected under any conditions. During hypoxia, coronary flow initially increased to 189.5 +/- 17.8% of the control, and at the same time release of all PGs, except for TXB2, increased significantly (6-keto PGF1 alpha: from 3.57 +/- 0.98 to 5.54 +/- 1.25 pmol/min.g, D2: from 1.47 +/- 0.26 to 2.22 +/- 0.26 pmol/min.g, E2: from 0.27 +/- 0.08 to 0.96 +/- 0.21 pmol/min.g, F2 alpha: from 0.23 +/- 0.09 to 0.48 +/- 0.13 pmol/min.g, TXB2: from 0.61 +/- 0.10 to 0.58 +/- 0.15 pmol/min.g). During the later phase (10-20 min) of hypoxia, coronary flow decreased without concomitant decrease in the release of PGs. The administration of indomethacin (10 microM) and aspirin (1 mM) did not affect the normoxic coronary flow. However, during the early phase of hypoxia, they significantly suppressed the increase in coronary flow. Administration of arachidonic acid (1 mg/l) increased PG release 6.4-12.5-fold and increased coronary flow to 176.1 +/- 6.5% of the control level. In the presence of arachidonic acid, there was a good correlation between the coronary flow and the amount of released vasodilative PGs (PGE2 and 6-keto PGF1 alpha), suggesting the contribution of these PGs to coronary vasoregulation. On the other hand, when hearts were made hypoxic in the presence of arachidonic acid, percentage increase in PG release was much reduced, and similarly, coronary flow was not elevated. These results indicate that the increase in coronary flow during the early phase of hypoxia is mediated, at least in part, by the increased release of vasodilative PGs. PMID- 1942093 TI - Effects of 2,3-butanedione monoxime (BDM) on contracture and injury of isolated rat myocytes following metabolic inhibition and ischemia. AB - The relationship between myocardial cell contracture and injury during total metabolic inhibition (amylobarbital and iodoacetic acid) and ischemia was examined, using 5-50 mM butanedione monoxime (BDM) as an inhibitor of contracture. BDM had no apparent effect on control myocytes during 180 min incubations, but inhibited contracture following anoxia or ischemia in a dose dependent fashion, as directly quantitated by length/width ratios. Cellular ATP levels decreased at a similar rate in the absence or presence of BDM, following metabolic inhibition. BDM-mediated inhibition of contracture was associated with accelerated cell injury, as defined by: the uptake of an extracellular marker (trypan blue) by the cardiomyocytes, by direct analysis of myoglobin released into the supernatant and by ultrastructural demonstration of defects in sarcolemmal membrane integrity. Calcium was not required for BDM's enhancement of injury, in that cells incubated in calcium free-EGTA buffer showed a similar BDM mediated acceleration of injury. In the presence or absence of calcium, enhancement of injury was more marked in cells osmotically stressed with a brief incubation in hypotonic buffer, than in cells resuspended in isotonic media. It is concluded that BDM enhances development of osmotic fragility of inhibited or ischemic cardiomyocytes and that contracture is not a necessary contributing factor to myocardial cell death. PMID- 1942094 TI - Effects of regional myocardial ischaemia on coronary artery calibre in the rabbit. AB - Microangiographic and electron microscopic studies were undertaken in isolated, perfused rabbit hearts to examine the effects of acute regional myocardial ischaemia on coronary artery calibre, vascular resistance and ultrastructure. Selective left coronary angiograms were recorded prior to, after 90 min of acute regional myocardial ischaemia induced by occlusion of the marginal left ventricular branch of the circumflex artery, and after reperfusion for 5 min. Vasodilation occurred in the proximal left anterior descending artery (9 +/- 1%, P less than 0.01) and the unoccluded part of the marginal branch (21 +/- 1%, P less than 0.001) during ischaemia which reversed on reperfusion. During reperfusion, coronary vascular resistance increased by 43 +/- 10% (P less than 0.001) despite mild vasodilation of vessels in the ischaemic zone (up to 10 +/- 1%, P less than 0.01). Failure of reperfusion occurred in vessels smaller than 30 microns in diameter (terminal arterioles) and was associated with ultrastructural damage in the ischaemic zone which was particularly prominent at the apex. These findings suggest that failure of reperfusion following 90 min of acute regional myocardial ischaemia in the rabbit is associated with damage to terminal arterioles and capillaries and that the calibre of the larger coronary vessels is maintained. Failure of reperfusion after prolonged myocardial ischaemia may occur despite arterial dilatation in the ischaemic zone. PMID- 1942095 TI - In situ localization of transforming growth factor beta 1 in porcine heart: enhanced expression after chronic coronary artery constriction. AB - We investigated the expression of transforming growth factor beta 1 (TGF-beta 1), a polypeptide differentiation factor probably associated with angiogenic properties in chronically hypoperfused heart tissue. A slowly swelling ameroid constrictor was implanted around the coronary circumflex artery (CX) of young domestic pigs. Two to three weeks after, significant CX stenosis of more than 90% and coronary collateralization could be demonstrated angiographically. The CX dependent experimental myocardial tissue (E) was investigated, with the LAD dependent area of the same pig serving as a control (C). We found significantly enhanced TGF-beta 1 mRNA expression by northern blot hybridization in the experimental myocardium (E) of those pigs with demonstrable coronary collaterals in the absence of a major myocardial infarction. The presence of TGF-beta 1 protein could be demonstrated quantitatively in extracts of the experimental and the control area by immunoblot analysis. By in situ techniques, TGF-beta 1 mRNA and protein could be localized predominantly in cardiac myocytes. We conclude that one adaptive mechanism of the pig heart in chronic coronary artery constriction is the enhanced expression of TGF-beta 1. Cardiac myocytes are a major source of TGF-beta 1. The observed coronary collateralization could be mediated-at least in part-by the angiogenic properties of TGF-beta 1. PMID- 1942097 TI - Quality: a Disney concern. PMID- 1942098 TI - Visual field loss and a relative afferent pupillary defect in a patient with optic nerve head drusen. AB - Optic nerve head drusen often cause several diopters of disc elevation and are important etiology of pseudopapilledema. Compression of nerve fibers between the lamina cribrosa and prelaminar drusen may cause corresponding visual field defects. Significantly asymmetric visual field loss may be associated with a relative afferent pupillary defect. Central visual field loss from optic nerve drusen is a rare phenomenon that requires an extensive ophthalmic work-up to rule out other pathology. PMID- 1942096 TI - The morphology of the developing canine conducting system: bundle branch and Purkinje cell architecture from birth to week 12 of life. AB - This is a qualitative and quantitative study of dog bundle branch and Purkinje cell development from day 0 to week 12 of life; we correlate the morphologic data with changes observed in the functional properties of developing dog Purkinje tissue. The bundle branch itself has a roughly cylindrical shape and is surrounded by a collagen sheath covered with endocardium. Within the bundle, Purkinje cells are packed closely together in fascicles distributed evenly around a central artery. Cross-sectional area doubles in the right bundle and increases 5-fold in the left bundle system between day 0 and week 12 of life. About one third of the bundle by volume is Purkinje tissue; the rest is extracellular space containing an increasing amount of collagen as the animal ages. Purkinje cell cross-sectional area is constant during the first week of life, but its length doubles and the cell changes from a relatively round to a more cylindrical shape. Between day 7 and week 12, cell diameter doubles; Purkinje cell surface area increases 5-fold and its volume almost 10-fold. As a consequence, the surface to volume ratio halves and approaches the value reported for adult dogs by week 12 of life. The percent of the intercalated disc occupied by nexal junctions virtually doubles by week 12, the same period over which Purkinje fiber conduction velocity increases. The disc itself becomes less dominant as the cell enlarges; the total percent of sarcolemma involved in its formation decreases by a fourth and has achieved the adult value by week 12 of life. As this happens, the percent of cell membrane facing on clefts increases almost 6-fold, so that the total percent of sarcolemma facing on small spaces (approximately 340A wide) is constant over the age period studied. The paucity of clefts in newborn tissue compared with the value reported for the adult dog may help explain the relative lack of responsiveness to extracellular potassium concentration of the resting membrane potential described for fetal Purkinje tissue. Within the Purkinje cell itself, the percent by volume occupied by mitochondria remains relatively constant over the age span studied, while sarcomeric mass increases 3-fold over the same period of time; these data are consonant with the relative resistance of this tissue to hypoxia. PMID- 1942099 TI - Evaluating postoperative cataract patients using the Kowa Flare Cell Meter. AB - The estimation of flare and cell in the anterior chamber is an important part of the postoperative care of patients who have had cataract surgery. The Kowa Flare Cell Meter uses a laser beam for a probe of light, lines it up precisely in a specially modified slit lamp, and controls and measures the results with a computer. The Kowa Flow Cell Meter incorporates a computer for input of demographics and a screen display and printer for output of the results. The anterior chamber findings are displayed both numerically and graphically. PMID- 1942100 TI - Enucleation and the hydroxyapatite orbital implant. AB - Hydroxyapatite is a natural, porous material that allows the recipient's blood vessels and fibrous tissues to grow onto the implant, thus becoming a "living" portion of the orbital tissues. Natural eye movement, resistance to extrusions, rare complications, and flexibility in fitting the socket are the reasons oculoplastic surgeons are using the hydroxyapatite implant. Hydroxyapatite spheres are contraindicated in situations where other types of orbital implants are contraindicated; ie, severe trauma with possible orbital infection orbits that have poor vascularization and healing qualities, such as after irradiation, and with orbital infection. PMID- 1942101 TI - Ciloxan for the management of corneal ulcers. AB - Bacterial keratitis (corneal ulcer) is a sight-threatening condition if not treated with the appropriate anti-infective agent. Treatment needs to be initiated with a broad-spectrum agent deemed to be most appropriate until culture results are obtained. If the suspected pathogen is staphylococci, streptococci, or Pseudomonas, Ciloxin is a new generation anti-infective agent considered highly effective against these pathogens. PMID- 1942102 TI - Infection following strabismus surgery. AB - Sixty-three strabismus surgeons were surveyed regarding the incidence of infection they found following strabismus surgery and their use of preoperative and postoperative antibiotics to prevent or treat such infections. Cellulitis was rare (1 per 1,900 cases) and endophthalmitis was even rarer (1 per 30,000 cases). Infection was not entirely prevented by either preoperative or postoperative topical antibiotics. Twelve surgeons reported using no antibiotics but did not report higher rates of infection than those who did use them. PMID- 1942103 TI - Basic ocular motility assessment. PMID- 1942104 TI - Childsight: helping children grow up with good vision. PMID- 1942105 TI - Handling contact lens emergencies. PMID- 1942106 TI - The past, the present, the year 2000, and beyond: inaugural address. PMID- 1942107 TI - Accessibility and availability to health care in the African-American community. PMID- 1942108 TI - Partial breast irradiation for early breast cancer. PMID- 1942109 TI - Health-care delivery to minority citizens: an update. PMID- 1942111 TI - The role of depression in hospital admissions and emergency treatment of patients with sickle cell disease. AB - Depression and demographic variables, ie, age, sex, and income were used to predict emergency treatment and hospital admissions of 46 patients with sickle cell disease. Depression was assessed using the Beck Depression Inventory. The results indicated that depression and age were significantly associated with emergency treatment and hospital admissions. Depression and age accounted for approximately 20% of the variance in explaining emergency treatment and 10% of the variance in explaining hospital admissions. PMID- 1942112 TI - The status of medical education for black Americans. AB - Health-care priorities are changing throughout the United States, and the quality of American medicine is dependent on the quality of medical education. While a surplus of doctors is anticipated, a shortage of minority doctors remains. Published data sources provide information on enrollment, distribution, and specialties of black Americans in medical education programs. These data provide understanding of the process that has created the shortage of blacks in medicine. The tabular data suggest that the proportion of blacks in medical education programs has remained very low over time, and in some cases, it has actually declined. Funding needs, recruitment efforts, and educational information are essential considerations in changing the racial make-up of medical education and health care. PMID- 1942110 TI - Attitudes toward condom use and AIDS among patients from an urban family practice center. AB - As part of an effort to better educate patients about using condoms, a survey was done to assess the sexual practices, attitudes toward acquired immunodeficiency syndrome (AIDS) and condom use by patients who visit an urban family practice center. A self-administered questionnaire was given to 126 patients of whom the majority were black and single. Seventeen percent indicated they had sex with more than one person in the 3 months before the survey. Within the last 5 years, 10% had sex with an intravenous drug abuser, and 6% with someone of the same sex. Fifty percent believed that condoms decrease sexual pleasure for men and 31% thought condoms made sex inconvenient. Twenty-seven percent of those surveyed believed that a man's penis may be too large for a condom and 18% believed that uncircumcised men could not use condoms. Forty-five percent believed they should be screened for human immune deficiency virus exposure. The results highlight attitudes and beliefs that may function as barriers to condom use and should be addressed when encouraging condom use with this population. PMID- 1942113 TI - End-stage renal disease and race: an overview and perspective. AB - The epidemiology of end-stage renal disease (ESRD) in the United States is reviewed. Hypertension and diabetes as etiologic factors in ESRD in minorities are discussed, as is the question of a familial ESRD. It is hypothesized that diuretics as sole antihypertensive therapy in blacks may in the long term result in chronic volume contraction, increased sympathetic stimulation, and therefore, decreased renal function. As such, a rational basis for the long-term use of diuretics as the sole antihypertensive therapeutic in blacks becomes questionable at best. PMID- 1942114 TI - Defining mental health needs for black patients with AIDS in Alameda County. AB - This study examines the impact of race and psychiatric symptomatology on the treatment of black patients with acquired immunodeficiency syndrome (AIDS). The study consisted of two parts: 1) focused group discussions with AIDS health professionals, and 2) a retrospective chart review of 44 hospitalized AIDS patients. The group discussions revealed that there are specific gaps in mental health services for all AIDS patients and that psychiatric and medical services must be delivered in an ethnically sensitive manner to be effective with black patients. The chart review revealed no statistically significant difference between black and white patients in terms of prevalence of psychiatric symptoms. The results of this study suggest that ethnically sensitive psychiatric diagnosis and treatment may have important clinical implications in the long-term management of black patients with AIDS. PMID- 1942116 TI - Spleen function in children with sickle B+ thalassemia. AB - Splenic function in patients with sickle B+ (SB+) thalassemia has been poorly documented. We evaluated the clinical course and splenic function in 12 children with SB+ thalassemia with simultaneous technetium sulfur colloid spleen scans and determination of pitted erythrocytes by direct interference contrast microscopy (DICM). All patients displayed normal uptake of radiocolloid. Mean percentage of pitted erythrocytes was 2.2% compared to 0.06% in 10 normal eusplenic controls and 13.8% in 10 sickle cell patients. In this group of children, who were carefully monitored for 136 patient years, there was no episode of bacteremia/sepsis, and a low prevalence of vaso-occlusive episodes. The slight increase in percentage of pitted erythrocytes of SB+ thalassemia patients does not seem to herald any clinically relevant loss of splenic function. SB+ thalassemia children younger than 10 years of age who do not seem to present a higher risk of invasive bacterial infections than eusplenic children, should receive conservative treatment for isolated febrile episodes and should not be submitted to prophylactic penicillin. PMID- 1942117 TI - Unilateral moyamoya disease, intracranial aneurysm, and a pituitary adenoma: a case report. AB - A case of unilateral moyamoya disease is reported in an adult, associated with an aneurysm of the circle of Willis and a nonfunctional pituitary adenoma. A review of the literature is discussed. Young individuals presenting with signs of acute cerebrovascular changes of undetermined cause should be evaluated for moyamoya disease. PMID- 1942115 TI - Common emergencies in cancer medicine: metabolic syndromes. AB - Metabolic derangements are fairly common occurrences in cancer medicine. In many instances, they require deft recognition and prompt institution of emergency therapeutic intervention. These syndromes may result from a primary tumor, metastatic disease, or anti-tumor therapy. This article discusses the management of such patients. PMID- 1942118 TI - Lest we forget. PMID- 1942119 TI - Pathology reevaluation of the Kociba et al. (1978) bioassay of 2,3,7,8-TCDD: implications for risk assessment. AB - The chronic bioassay of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) reported in 1978 by Kociba et al. has been considered to be the primary evidence supporting its carcinogenicity, and is the basis for most dioxin regulations in North America and Western Europe. Because the histopathological criteria for proliferative lesions in the rat liver have changed significantly since 1978, a reevaluation of the liver slides was conducted recently by an independent panel of pathologists. Using current National Toxicology Program criteria, their study showed, in contrast to the original findings, that about two-thirds fewer tumors were present in the livers of female Sprague-Dawley rats. The no-observed-adverse effect level (NOAEL) for hepatocellular carcinomas was 0.01 micrograms/kg/d rather than 0.001 micrograms/kg/d, which had been reported in 1978. In light of these significant findings, a quantitative dose-response assessment of 2,3,7,8 TCDD was undertaken to predict the potential carcinogenic risks to humans. Risk specific doses (RsDs) and cancer potency factors (CPFs) were calculated by applying the linearized multistage (LMS) model to the combined incidences of hepatocellular carcinomas and adenomas, classified in accordance with the 1990 histopathological criteria. Based on the weight of evidence regarding the mechanism of action of 2,3,7,8-TCDD, body weight rather than surface area was selected as the appropriate means for scaling rodent data to predict the human response. Using the survival-adjusted data, the RsD for a 1 in 1,000,000 (10(-6)) plausible upper bound (95%) lifetime incremental cancer risk was 370 fg/kg/d based only on the incidence of hepatocellular carcinomas, and 100 fg/kg/d when hepatocellular carcinomas and adenomas were combined. The corresponding upper bound (95%) CPFs were 2700 and 9700 (mg/kg/d)-1, respectively. These results indicate that the carcinogenic risk to humans from exposure to 2,3,7,8-TCDD is at least 16-fold lower than previous estimates derived from the Kociba et al. (1978) bioassay. PMID- 1942120 TI - Acute toxicity, genotoxicity, and dermal carcinogenicity assessment of isooctyl acrylate. AB - Isooctyl acrylate (IOA) monomer is a complex mixture comprised predominantly of isomeric, eight-carbon alkyl esters of acrylic acid. Limited evidence from animal studies suggests that certain acrylate esters may be carcinogenic by the dermal route of exposure. The following studies were performed with IOA monomer: acute oral toxicity limit test in rats, primary dermal and ocular irritancy in rabbits, Ames Salmonella microsome assay, Saccharomyces cerevisiae D3 recombinogenicity assay, L5178Y TK +/- mouse lymphoma cell assay, and C3H/10T1/2 mouse embryo cell transformation assay. Finally, a limited dermal carcinogenicity bioassay was performed in which aliquots (25 microliters) of IOA monomer (5% v/v in acetone), IOA polymer (19% w/v in 70:30 acetone/heptane), or acetone (vehicle control) were applied to the shaved backs of male C3H/HeJ mice three times per week for the animals' lifetimes. IOA monomer had an acute oral LD50 in rats greater than 5000 mg/kg, was slightly irritating to the eyes and skin of rabbits on single exposures, and exhibited no genotoxic or cell-transforming potential. In the dermal carcinogenicity bioassay, no significant difference in mean survival times was observed between either treatment group and the control group. Animals treated with IOA monomer exhibited moderate dermatitis, surface crusting, hyperkeratosis, epidermal hyperplasia, diffuse melanosis, and one benign melanoma at the treatment size. Animals treated with IOA polymer exhibited varying degrees of dermatitis, surface crusting, and hyperkeratosis. Neither IOA monomer nor IOA polymer was carcinogenic under the conditions of the study. PMID- 1942121 TI - Aflatoxicosis alters avian renal function, calcium, and vitamin D metabolism. AB - Experiments were designed to determine the effects of aflatoxicosis on avian renal function, calcium (CA), inorganic phosphorous (Pi), and vitamin D metabolism, and to determine if the effects of aflatoxin are reversible upon discontinuation of toxin administration. Three-week-old male broiler chickens (n = 12 per treatment) received aflatoxin (AF; 2 mg/kg po) or an equal volume of corn oil, the AF carrier vehicle, for 10 consecutive days. After 10 d of treatment, half of the birds from each treatment group were anesthetized and prepared for renal function analysis, which included a 2-h phosphate loading period. Ten days after discontinuation of AF treatment, the remaining birds in each treatment group were anesthetized and prepared for renal function analysis. AF decreased plasma 25-hydroxy vitamin D [25(OH)D] and 1,25-dihydroxy vitamin D [1,25(OH)2D] levels after 5 d of treatment. After 10 d of treatment, urine flow rate (V), fractional sodium excretion (FENa), and fractional potassium excretion (FEK) were lower in AF-treated birds. In addition, total plasma Ca tended to be lower (p = .10) and fractional Ca excretion (FECa) tended to be higher (p = .10) in the AF-treated birds. Intravenous phosphate loading produced a sharp increase in urine hydrogen ion concentration ([H+]) in the AF-treated birds. Glomerular filtration rate (GFR) was reduced and plasma osmolality was increased in AF treated birds 10 d after discontinuation of toxin administration. The results indicate that AF directly or indirectly affects Ca and Pi metabolism in avians. At the present time, the effects may be related to altered vitamin D and parathyroid hormone (PTH) metabolism. Aflatoxicosis may decrease endogenous PTH synthesis and the renal sensitivity to PTH. The AF-related increase in urine [H+] during phosphate loading is probably due to increased Na+/H+ counterport, suggesting that AF stimulates sodium reabsorption. Also, the decrease in GFR exhibited 10 d after toxin removal indicates that AF may cause prolonged alteration in renal function. PMID- 1942122 TI - Developmental toxicity of diphenyl ether herbicides in nestling American kestrels. AB - Beginning the day after hatching, American kestrel (Falco sparverius) nestlings were orally dosed for 10 consecutive days with 5 microliters/g of corn oil (controls) or one of the diphenyl ether herbicides (nitrofen, bifenox, or oxyfluorfen) at concentrations of 10, 50, 250, or 500 mg/kg in corn oil. At 500 mg/kg, nitrofen resulted in complete nestling mortality, bifenox in high (66%) mortality, and oxyfluorfen in no mortality. Nitrofen at 250 mg/kg reduced nestling growth as reflected by decreased body weight, crown-rump length, and bone lengths including humerus, radius-ulna, femur, and tibiotarsus. Bifenox at 250 mg/kg had less effect on growth than nitrofen, but crown-rump, humerus, radius-ulna, and femur were significantly shorter than controls. Liver weight as a percent of body weight increased with 50 and 250 mg/kg nitrofen. Other manifestations of impending hepatotoxicity following nitrofen ingestion included increased hepatic GSH peroxidase activity in all nitrofen-treated groups, and increased plasma enzyme activities for ALT, AST, and LDH-L in the 250-mg/kg group. Bifenox ingestion resulted in increased hepatic GSH peroxidase activity in the 50- and 250-mg/kg groups. Nitrofen exposure also resulted in an increase in total plasma thyroxine (T4) concentration. These findings suggest that altricial nestlings are more sensitive to diphenyl ether herbicides than young or adult birds of precocial species. PMID- 1942124 TI - Differential DNase I hypersensitivity of ras oncogenes in B6C3F1, C3H/He, and C57BL/6 mouse liver. AB - The male hybrid B6C3F1 mouse exhibits a 30% spontaneous hepatoma incidence, whereas the paternal C3H/He strain and the maternal C57BL/6 strain exhibit a 60% and a negligible incidence, respectively. In addition, both male and female B6C3F1 mice are extremely sensitive to chemical induction of hepatocarcinogenesis. The Ha-ras, Ki-ras, and myc oncogenes have been implicated in a variety of solid tumors. Specifically, Ha- and, less frequently, Ki-ras have been reported to be activated in B6C3F1 mouse liver tumors. The objective of this study was to examine a possible point of transcriptional control of Ha-ras, Ki ras, and myc in all three mouse strains, our hypothesis being that these oncogenes may be primed for expression in the nascent liver of those strains exhibiting a high spontaneous hepatoma incidence. A positive correlation has been established between gene expression and the presence of DNase I hypersensitive sites. DNase I hypersensitive sites were observed in the Ha-ras and myc oncogenes in the three mouse strains. However, Ha-ras appears to possess an additional site in B6C3F1 and C3H/He as compared to C57BL/6. Similarly, the Ki-ras oncogene exhibited a DNase I hypersensitive site only in B6C3F1 and C3H/He mouse liver. These results indicate that the hepatoma-prone strains (B6C3F1 and C3H/He) may have a greater potential for Ha- and Ki-ras expression than does the non-hepatoma prone strain (C57BL/6). PMID- 1942123 TI - Sulfuric acid-layered ultrafine particles potentiate ozone-induced airway injury. AB - Urban air pollution in the United States is composed of a complex mixture of particles and gases. Among the most prominent products of the atmospheric pollutants are sulfur oxides and ozone. In this report, we use two exposure protocols to examine the interaction between exposure to these two pollutants. In the first exposure regimen, guinea pigs were exposed to sulfuric acid (pure sulfuric acid mist or sulfuric acid layered on ZnO) for 1 h. Each exposure is followed 2 h later by another exposure to 0.15 ppm ozone for 1 h. Pulmonary function parameters were measured immediately after the ozone exposure. In guinea pigs that were exposed to 300 micrograms/m3 pure sulfuric acid mist, subsequent exposure to 0.15 ppm ozone did not produce additional change in pulmonary functions. In guinea pigs that were exposed to 84 micrograms/m3 sulfuric acid layered on ZnO, subsequent exposure to 0.15 ppm ozone produced more than additive alterations in vital capacity and diffusing capacity. In the second exposure regimen, guinea pigs were exposed to 24 micrograms/m3 sulfuric acid layered on ZnO for 3 h/d for 5 d. On d 8 and 9, animals received two additional daily 3-h exposures to 24 micrograms/m3 sulfuric acid layered on ZnO, and pulmonary functions were measured at the end of the daily exposure. Greater reductions in lung volumes and diffusing capacity were observed in animals on d 9 than would be observed in animals that received no additional exposure. In the third exposure regimen, guinea pigs were exposed to 24 micrograms/m3 sulfuric acid layered on ZnO for 3 h/d for 5 d. On d 9, animals were exposed to 0.15 ppm ozone for 1 h and pulmonary functions were measured at the end of the ozone exposure. Ozone exposure on d 9 induced reductions in lung volumes and diffusing capacity that were not observed in animals receiving exposures to either ozone or sulfuric acid layered ZnO alone. We conclude that single or multiple exposure to sulfuric acid layered ZnO sensitizes guinea pigs to subsequent sulfuric acid or ozone exposure. PMID- 1942125 TI - Relationship between chlorofluorocarbon chemical structure and their Salmonella mutagenicity. AB - This paper is a quantitative analysis of the relationship between the chemical structure and the Salmonella mutagenicity of a number of chlorofluorocarbons (CFC). The molecules were characterized by both molecular orbital and physical chemical parameters. The results of the analysis indicated that the CFC mutagenicity is correlated with two parameters: the free energy of binding to biological receptors, and the energy of the highest occupied molecular orbital (HOMO). Since these are the same factors that would favor the cytochrome P-450 catalyzed metabolism, it would appear that the CFC mutagenicity is determined more by the rate of initial activation than by the rate of DNA attack. PMID- 1942126 TI - Does one have to learn to crawl before he can learn to walk? PMID- 1942127 TI - Computer tomography (CT) applications in implant dentistry. PMID- 1942128 TI - Anatomic considerations for dental implants. AB - The shape, quantity, and quality of bone in the mandible and maxilla are significant factors in deciding which implant options are possible. An understanding of the importance of each of these factors is necessary for the successful diagnosis of edentulous and partially edentulous arches and for optimum use of the many devices and concepts being promoted to the profession and the public. This paper will discuss the differences between the bone of the mandible and the maxilla and between the dentulous and edentulous areas and how these affect implant treatment. Reestablishment of bone in deficient areas is also discussed. PMID- 1942129 TI - Extension and containment of infections secondary to dental implant procedures. PMID- 1942130 TI - Multi-tubular bi-sectional interlocking maxillary subperiosteal implants. PMID- 1942131 TI - Biomechanical load analysis of cantilevered implant systems. AB - Historically, dental implants have been placed in areas where quality bone exists. The maxillary sinus areas and mandibular canal proximities have been avoided. From these placements, various cantilevered prosthetic applications have emerged. This analysis uses static engineering principles to define the loads (i.e., forces) placed upon the implants. These principles make use of Newton's first and third laws of mechanics by summing the forces and moments to zero. These summations then generate mathematical equations and their algebraic solutions. Three implant systems are analyzed. The first is a two-implant system. The second is a three-implant cross-arch stabilized system usually found in mandibular replacements of lower full dentures. The third is a five-implant system which is identical to the three-implant cantilevered system but which uses implants in the first molar area, thereby negating the cantilevered load magnification of the three-implant design. These analyses demonstrate that, in a cantilevered application, the implant closest to the point of load application (usually the most posterior implant) takes the largest compressive load. Implants opposite the load application (generally the anterior implant) are in tension. These loads on the implants are normally magnified over the biting force and can easily reach 2 1/2 to five times the biting load. PMID- 1942132 TI - Osseo-integration of dental implants in radiated mandibles: an experimental study with beagle dogs. AB - This investigation was planned to detect the ability of radiated bone to integrate with dental implants and to study the load-bearing capacity of these implants. In five beagle dogs, the premolars were extracted, after which one side of the mandible was radiated with 40 Gy. Three months later, two hollow-cylinder implants were placed on each side of the mandible. After a three-month period of osseo-integration, bridges were constructed on the implants, and they were loaded for six months. Both clinical and x-ray examinations showed that all implants had integrated well and bore load without change in their host sites for a six-month period, at which time the dogs were killed. PMID- 1942133 TI - Implant registry and implant retrieval service. PMID- 1942134 TI - Experimental studies on the pharmacokinetics and nephrotoxicity of carboplatin (cis-diammine-1, 1-cyclobutane dicarboxylate platinum II) in rats. AB - To study the nephrotoxicity of carboplatin (cis-diammine-1, 1-cyclobutane dicarboxylate platinum II, CBDCA), an analogue of cisplatin, we examined its pharmacokinetics and functional and histopathological changes of the kidney in rats that received i.v. injection of carboplatin. Platinum concentrations in the whole plasma rapidly decreased during the first 2 hours and was undetectable at 72 hours following the carboplatin administration. Approximately 90% of the platinum in the whole plasma was ultrafilterable during the first 30 minutes. The renal tissue concentrations of platinum rapidly decayed during the first 4 hours and then slowly declined up to 120 hours following the carboplatin administration. Platinum concentrations in the renal cortex showed higher levels than those in the renal medulla throughout the experimental period. BUN levels were within the normal range except on day 7. Serum creatinine levels remained stable and normal during the 7 days. Histopathological alterations of the renal tubules were not observed during the experimental period. These results suggest that carboplatin has less nephrotoxicity than cisplatin, because of its rapid excretion through glomerulus and less accumulation in the tubular cells. PMID- 1942135 TI - Studies on eye irritation caused by chemicals in rabbits--II. An in vitro testing method using rat red blood cells for the prediction of eye irritation potential of chemicals. AB - Rat red blood cells were used as an in vitro method to evaluate the eye irritation potential of chemicals in rabbits. The results using 116 chemicals of various categories including medicines, pesticides, detergents and solvents were analyzed for the prediction of possibility of eye irritation potentials. Eye irritation of chemicals was examined according to Draize method and chemicals were classified into three categories, (1) non or mild irritants, (2) moderate or severe irritants and (3) strong or corrosive irritants, based on the recovery of damages. The in vitro method consisted of two methods detecting the effects of chemicals mainly on protein and lipid in the membrane, which were evaluated by the induction of methemoglobin and hemolysis, respectively. Non- or mild irritants induced neither methemoglobin formation nor hemolysis. Most of moderate or severe irritants induced hemolysis, however, the potentials were low. Strong or corrosive irritants had high potentials for the induction of methemoglobin. The multivariate estimation by the above two in vitro data sets were 77.6% predictive of the in vivo classification. PMID- 1942136 TI - Effect of estrogen replacement on liver function in ovariectomized rats. AB - The effect of estrogen (17 beta-estradiol; E2) replacement on the liver function was examined in ovariectomized rats. Ovariectomy decreased serum transaminase activity and physiological dosage levels of E2 replacement returned the activity up to or above non-ovariectomized levels. Under the conditions of this experiment the elevated serum transaminase levels in the E2 replacement were not coincident with histological changes suggestive of liver dysfunction. The elevations of both serum glutamic oxaloacetic transaminase (GOT) and serum mitochondrial GOT were accompanied by increased hepatic tissue activity, suggesting that the elevated serum levels can be attributed to the accelerated synthesis of the enzymes. On the other hand, the elevation of serum glutamic pyruvic transaminase was not accompanied by increased tissue activity in the original organs, namely liver, kidney, heart and skeletal muscle. Ovariectomy decreased serum albumin and inhibited development of rough endoplasmic reticulum in the liver, and E2 replacement returned them up to or above the non-ovariectomized levels. PMID- 1942137 TI - The pattern of injury to rear seat passengers involved in automobile collisions. AB - This retrospective study analyzed the pattern of injury among rear seat occupants in automobile collisions and compared the incidence and type of injury with that of front seat occupants. During a 2-year study period, 253 persons involved in automobile collisions were admitted to our hospital. Among these patients 168 were drivers, 54 were front seat passengers, and 24 were rear seat occupants. Injuries were classified into the following categories: neurologic, orthopedic, soft tissue, thoracic, and abdominal. No significant differences were observed in the type or extent of injury, in the incidence of permanent disability, or in the mortality rate based on the location of the passengers within automobiles involved in these crashes. PMID- 1942138 TI - Tolerance to steering wheel-induced lower abdominal injury. AB - Anesthetized swine were tested for biomechanical and injury responses to lower abdominal steering wheel loading. The lower abdomens of 25 subjects were impacted with a segmented steering wheel. Tests included a wide spectrum of velocities, from 1.7 to 12.4 m/s, and forced abdominal compressions of 7.0%-54.5% of the vertical thickness of the lower abdomen. Lower abdominal injuries included contusions and lacerations of varying severity and frequency in the mesentery, the small and large bowel, the spleen, and the cecum. Logistic regression correlations were performed to assess the probability of severe and greater injury with biomechanical indices such as peak velocity of deformation (Vmax), peak compression (Cmax), peak total force (Fmax), the maximum Viscous criterion (VCmax), and the product of maximum total force and maximum compression (FmaxCmax). Although Cmax, Fmax, and, to a lesser extent, FmaxCmax correlated reasonably well with the probability of severe and greater injury, the maximum Viscous criterion (VCmax) was the best correlate, establishing VCmax as the most effective predictor of an AIS greater than or equal to 4 injury risk for steering wheel loading to the lower abdomen. PMID- 1942139 TI - Trauma in the arctic: an incident report. AB - On January 29, 1989, a military aircraft crashed on approach to an airfield in Alaska. The subsequent extraction, evacuation, and casualty resuscitation occurred at temperatures lower than -50 degrees F. Both the medical and military literature are replete with instructions and advice regarding the handling of trauma victims in the field in the Arctic environment; however, case reviews of such incidents are rare. In this case, the circumstances of the incident, and the organizations on which it fell, argued for almost ideal handling of the care of the victims. Problems that have an impact on the availability of casualty management, generally, in the Arctic such as a widely scattered population and sparse medical facilities, poorly defined evacuation routes, and marginal communication patterns, were not encountered in this review because of the unusual circumstances of this incident. The difficulties of field care in this environment, even under "ideal" conditions, however, are real and evident in this case history. Transportation assets are critical. Rehearsal, critique, refinement, and re-rehearsal of a mass casualty plan can significantly increase victim survival. Proper protocols and confidence in them take on an importance far beyond their benefit in a more temperate environment. Procedures must be worked out in advance, known by all concerned, and practiced, because the "rescuer" is at the same risk of hypothermia as the "victim" and, in addition, is responsible for thinking for the incapacitated patient. Rote-learned drills will be acknowledged far longer in the cold than unspecific guidelines. Survival for trauma victims may depend on those rote actions. PMID- 1942140 TI - Pediatric falls from heights. AB - Injuries resulting from falls from heights still constitute a significant portion of urban trauma. At this pediatric trauma center, 70 children were admitted from 1985 to 1988 after sustaining a fall of 10 feet or greater or at least one story. The mean patient age was 5 years and 68% of the patients were boys. Seventy-eight percent of falls occurred from 2 stories or less and usually took place at or near the home. Most patients sustained a single major injury and all survived. The majority of injuries involved the head or skeleton and residual functional deficits were uncommon. The incidence of falls from heights has remained high in urban areas despite public education and building codes that require window guards and safety rails. PMID- 1942141 TI - Injuries in infants and small children resulting from witnessed and corroborated free falls. AB - The height of a free fall necessary to cause injury to infants and small children is a confusing and controversial issue among health care, law enforcement, and legal professionals responsible for evaluating cases of possible child abuse. To resolve this confusion, the circumstances of falls were recorded prospectively for 398 consecutive victims of falls seen at Children's Hospital, Oakland, California. From these cases, 106 were selected for further analysis where the falls were witnessed by a second person other than the caretaker and the circumstances of the fall were documented. No injuries occurred in 15 patients, including seven falling more than 10 feet. Mild bruises, abrasions, or simple fractures occurred in 77 patients, including 43 falling more than 10 feet. Severe injuries, including intracranial hemorrhages, cerebral edema, depressed skull fractures, and compound or comminuted fractures occurred in 14 patients falling between 5 and 40 feet. However, no life-threatening injuries occurred in the 3 patients who fell less than 10 feet. These three had small, depressed skull fractures without loss of consciousness, from falling against an edged surface. Only one death occurred in this series, resulting from a fall of 70 feet. In conclusion, infants and small children are relatively resistant to injuries from free falls, and falls of less than 10 feet are unlikely to produce serious or life-threatening injury. PMID- 1942142 TI - Deaths from falls in children: how far is fatal? AB - The outcome of injury was determined in 317 children who were brought to a children's trauma center with a history from the caretaker that the child had fallen. Cases in which the clinicians' judgment was that an incorrect history had been given were included along with cases in which the history was not questioned. Seven deaths occurred in 100 children who fell 4 feet or less. One death occurred in 117 children who fell 10 feet to 45 feet. The 7 children who died in short falls all had other factors in their cases which suggested false histories. When children incur fatal injuries in falls of less than 4 feet, the history is incorrect. Long falls with an outdoor component are likely to be reliable data points for studies of children's injuribility. PMID- 1942143 TI - Elevated initial blood glucose levels and poor outcome following severe brain injuries in children. AB - To determine whether elevations in blood glucose levels were related to neurologic outcomes following severe brain injuries in children, 54 patients 16 years of age or younger admitted to a regional trauma center with a Glasgow Coma Scale score of 8 or less over a 2-year period were retrospectively reviewed. The mean initial blood glucose level on hospital admission was significantly higher in the 16 patients with outcomes of death or vegetative state in comparison with that of the 38 patients with outcomes of good recovery, moderate disability,or severe disability (288 mg/100 mL vs. 194 mg/100 mL, t = -2.74, p = 0.01). Blood glucose levels correlated significantly with indicators of the severity of the brain injury, which were also related to outcome. In contrast, blood glucose levels did not correlate with indicators of the severity of the extracranial injuries, although the latter were significantly related to outcome. Logistic regression analysis resulted in a model for prediction of outcome which included the Glasgow Coma Scale score on admission and the initial blood glucose level. The odds ratio of a poor outcome in this model in patients with blood glucose levels greater than or equal to 250 mg/100 mL relative to those with lower levels was 8.3 (95% confidence interval 1.3-53.6). A simple prognostic score was derived from the logistic regression which improved upon the prediction of outcome using the Glasgow Coma Scale score alone in those patients with initial blood glucose levels greater than or equal to 250 mg/100 mL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942144 TI - Behavioral disturbances in children after trauma. AB - The psychological effects of nonneurologic trauma on children are poorly recognized. We hypothesized that physical trauma in children, with or without head injury, would result in substantial and persistent psychological and behavioral abnormalities. Using a short telephone survey followed by a detailed behavioral checklist, we studied psychobehavioral dysfunction in children who had experienced trauma either with or without minor head injury (n = 40 each) as well as in a comparative group of children after emergency appendectomy (n = 80). Substantial behavioral disability was identified by the detailed checklist in 35% and 28% of children without and with head injury, respectively, but in none after appendectomy. Dysfunctions included phobias, major scholastic difficulties, rage attacks, and episodic depression that continued for a long period. Even in the 67% of children who eventually fully recovered, the duration of symptoms after the time of injury was an average of 19 months. Demographics, socioeconomic status, severity of injury, and length of hospitalization did not correlate with dysfunction, and these traumatized children's siblings had no reported history of trauma or psychological difficulties. Thus, parental opinion about behavioral dysfunction appears sensitive and specific and is therefore a useful screening index. These results suggest that injured children, even after minor trauma, may suffer substantial and long-lasting behavioral changes to a degree hitherto unrecognized. PMID- 1942145 TI - A comparison of EMT judgment and prehospital trauma triage instruments. AB - A number of instruments have been devised to aid in the triage of trauma patients. Little work, however, has been done to demonstrate that these triage instruments offer an advantage over the judgment of an emergency medical technician (EMT) in determining which patients require transportation to a trauma center. The purpose of this study was to compare EMT judgment against three scoring systems; the triage-revised Trauma Score, the Prehospital Index, and the CRAMS scale. Data were gathered on trauma victims transported by the City of Cleveland EMS system. The EMTs rated the patient's overall severity on a 4-point scale and estimated the probability of patient mortality. We found that the EMT prediction of mortality was as accurate as the various scores. In a subset of patients, we also found that the EMT assessment performed as well as the scoring systems in identifying patients who either died or required emergent operative intervention. We conclude that EMT judgment is as accurate as these three scoring systems in identifying patients at high risk for death or the need for immediate operative intervention. PMID- 1942146 TI - Effects of anesthesia, surgery, fluid resuscitation, and endotoxin administration on postburn bacterial translocation. AB - The aim of the study reported here was to assess the effects of some clinically relevant factors on the incidence and outcome of postburn bacterial translocation. Miniature pigs in 8 groups (n = 6 in each) underwent: (1) general anesthesia (GA); (2) operation (insertion of Swan-Ganz, arterial, and portal catheters) under GA; (3) burn (40% total body surface area, third degree, under GA); (4) burn and operation; (5) burn, operation, and resuscitation (Parkland); (6) burn, operation, and resuscitation plus endotoxin (100 micrograms/kg IV bolus, 2nd day). Groups 1-6 were killed at 48 hours and tissue samples were harvested for bacteriologic culture. Groups 7 and 8 were the same as 2 and 5, respectively, but were killed at 96 hours. Resuscitation and endotoxin increased postburn bacterial translocation but only endotoxin promoted systemic sepsis. In the absence of additional trauma, translocated bacteria were cleared by 96 hours postburn. PMID- 1942147 TI - New Mexico rattlesnake bites: demographic review and guidelines for treatment. AB - The demographic features, treatment, and outcome of 36 rattlesnake envenomation cases are reviewed. Two populations at special risk are identified: (1) young children (12/36) who sustain lower extremity bites, and (2) adults who consume alcohol and handle snakes (10/36) who sustain upper extremity bites. Antivenin was used in 22 cases with only one serious case of serum sickness. Three definite diagnoses of compartment syndrome were made on the basis of elevated compartment pressures. Hand bites accounted for 20 of the 36 cases. The greatest functional disability followed digit bites in that 11 patients developed decreased motion and sensation. The indications for fasciotomy and debridement are discussed, both for digit and non-digit envenomations. General treatment recommendations are given. PMID- 1942148 TI - Cardiac injury complicating traumatic asphyxia. AB - During a 3-year period (1986-1989), 8 patients were seen at St. Louis University Medical Center exhibiting the stigmata of traumatic asphyxia. Fewer than 200 cases of traumatic asphyxia have been reported and there is only a single report of a cardiac injury. In this series, 3 of 8 (37.5%) patients were found to have an injury to the heart: two cardiac contusions and a ventricular rupture. Five patients were crushed in motor vehicle collisions, one by an elevator counterweight, and two patients by river barges. Injuries associated with these patients include pulmonary contusion, hemopneumothorax, traumatic pneumatocele, traumatic retinopathy, bone fractures, mental confusion, and liver contusion. There was one death in the series, a patient with rupture of the right ventricle and severe splenic and liver injuries. The cardiac status of the patients was evaluated by serial serum cardiac enzyme determinations, electrocardiograms, and echocardiography. This report illustrates the importance of complete cardiac evaluation in patients with traumatic asphyxia. PMID- 1942149 TI - Intraoperative decision-making in renal trauma surgery. AB - Surgery for renal trauma requires three intraoperative decisions: Should the kidney be explored? Is pedicle control necessary? What procedure should be performed? In 85 explorations for penetrating (66) and blunt (19) trauma, we found that penetrating injuries, active hemorrhage, or major tissue destruction are reasons for mandatory renal exploration. This resulted in 26 nephrectomies, 9 partial nephrectomies, and 4 major renorrhaphies. Forty-six patients underwent minor renorrhaphy or needless exploration without complications. Formal pedicle control was carried out 33 times (39%), but it was never necessary to control parenchymal hemorrhage. Unless a wound overlies the great vessels, perirenal hematomas can be safely entered laterally without prior pedicle control using manual pedicle or parenchymal control if needed. PMID- 1942150 TI - The diagnostic value of interpediculate distance assessment on plain films in thoracic and lumbar spine injuries. AB - In a retrospective study of 107 fractured vertebrae in the thoracic and lumbar spine, the interpediculate distance could be accurately assessed on plain roentgenograms in 96%. When these findings were compared with those of conventional tomography, there were no false-positive or false-negative results concerning normal or increased interpediculate distance. In 22 injured vertebrae the increased interpediculate distance was measured. In all these cases there was a fracture of the pedicle or lamina in addition to an injury of the vertebral body. We conclude that interpediculate distance can almost always be assessed and that an increased interpediculate distance on plain films is 100% reliable as an indicator of damage to the vertebral body, the pedicle, or lamina. PMID- 1942151 TI - Low initial hemoglobin levels in trauma patients: an important indicator of ongoing hemorrhage. AB - The initial hemoglobin (Hb) levels and vital signs of 1,000 patients treated with intravenous infusion in the admission area of Groote Schuur Hospital Trauma Unit were recorded. The mean Hb level of 860 patients with mild or no signs of shock was 12.7 g/dL. Lower mean Hb levels were noted in 91 moderately shocked patients (11.8 g/dL, p less than 0.0001) and 49 severely shocked patients (9.9 g/dL, p less than 0.00001). In 140 patients with systolic blood pressure (SBP) under 80 mm Hg on admission, mortality was increased in those with a Hb level under 8 g/dL (p less than 0.001), and a reduced mean Hb level was observed in 11 who died of hypovolemia (6.8 g/dL) compared with 6 dying of nonhypovolemic causes (11.7 g/dL), 10 dying of multiple causes (10.2 g/dL), or 113 survivors (11.7 g/dL, p less than 0.000001). In 31 patients with initial Hb levels of less than 8 g/dL, the overall mortality was 48.4%, compared with 2.6% in 969 patients whose initial Hb level was 8 g/dL or more (p less than 0.00001). Hypovolemia was judged to be the major factor in causing death in 13 (86.7%) of the 15 patients with a Hb level under 8 g/dL who died. A low Hb level observed soon after injury is usually an indicator of serious ongoing hemorrhage and has important implications for management and prognosis. Measurement of the Hb level may prove useful in prehospital assessment of the level of trauma care required and also in injury severity scoring as a predictor of mortality. PMID- 1942152 TI - Impact of the use of absorbable fracture fixation implants on consumption of hospital resources and economic costs. AB - Within a 6-year period (1984-1989) absorbable pins, rods, and screws made of polyglycolide, polylactide, or lactide-glycolide copolymer were used in the internal fixation of 881 fractures, 73.1% of which were displaced malleolar fractures of the ankle. During the last 3 years the patients treated using absorbable fracture fixation constituted 19.6% of all fracture patients managed by internal fixation at the department. The number of hardware removal procedures avoided during the 6-year period as a result of the use of the absorbable implants was estimated at approximately 700. By determining all direct and indirect costs associated with internal fracture fixation and the influence of the percentage of hardware removal, a cost coefficient was calculated for certain fracture types when treated using absorbable versus metallic internal fixation. In bimalleolar fractures, an optimal indication for absorbable fixation, the coefficient was 1.04 (cost of absorbable fixation 4% higher than that of metallic fixation) if the removal percentage with metallic fixation was zero and 0.91 (cost of absorbable fixation 9% lower than that of metallic fixation) if the removal percentage was 100%. The breakeven point was a removal rate of 31%. PMID- 1942153 TI - A new technique of catheter placement for measurement of forearm compartment pressures. AB - Hitherto described techniques of catheter placement in the forearm for compartment pressure measurement in the evaluation of forearm compartment syndrome place the underlying neurovascular structures at risk for injury. Based on the cross-sectional anatomy of the forearm, two previously undescribed routes are detailed that provide safer access to the deep volar forearm compartment. Via the ulnar approach, the catheter is inserted medial to the subcutaneous border of the ulna and advanced radially, transversely, skimming over the volar aspect of the ulna into the belly of flexor digitorum profundus. Via the dorsal approach the catheter is inserted radial to the subcutaneous border of the ulna in the supinated forearm. Using the ulna as a guide the catheter is advanced through the dorsal forearm compartment and interosseous membrane into the deep volar compartment. By this route, pressures of both dorsal and volar compartments of the forearm can be measured with a single catheter insertion. PMID- 1942154 TI - Two cases of tension pneumopericardium following blunt chest injury. AB - Tension pneumopericardium is uncommon in blunt trauma, and only rare survivors have been reported. We report two patients who survived tension pneumopericardium following blunt trauma. Both patients experienced signs and symptoms of cardiac tamponade that were corrected by insertion of a subxyphoid pericardial tube. Both survived all injuries and returned to normal activities with normal neurologic function. PMID- 1942155 TI - Bilateral tibial fractures in properly restrained toddlers involved in motor vehicle collisions: case reports. AB - It is well documented that the use of child restraints, specifically child safety seats, can reduce morbidity and mortality in young victims of motor vehicle crashes. Literature review reveals few extremity fractures in properly restrained toddlers. Of 10 restrained infants involved in car crashes admitted to our hospital, 4 had leg fractures. We report 2 cases of bilateral tibial fractures in restrained toddlers in which the usual clinical signs of fracture were minimal or lacking. A high index of suspicion must be maintained in evaluating even properly restrained toddlers in motor vehicle crashes. PMID- 1942157 TI - Carinal injury: diagnosis and treatment--case report. AB - Injury to the thoracic trachea is a potentially lethal condition in a patient with multiple injuries. Several clinical signs are commonly associated with this process: subcutaneous emphysema, aphonia, stridor, pneumothorax refractory to thoracostomy tube drainage, pneumomediastinum, and hemoptysis. The clinical appearance of tracheobronchial rupture may be delayed for hours or even weeks following injury. Standard treatment for disruption of the thoracic trachea is primary repair via a right thoracotomy. We describe a patient with a complex carinal injury following blunt thoracoabdominal trauma who was successfully managed with prompt surgical intervention. PMID- 1942156 TI - Acute management of traumatic forequarter amputations: case reports. AB - Traumatic forequarter amputation is a rare and very devastating injury. The arm, including the scapula, clavicle, and pectoral muscle, is torn from the body by a tremendous traction force, usually combined with a counteracting force from the body. The cases of three patients are presented. One patient was caught by the axle of a harvesting machine, resulting in a forequarter amputation of his right extremity and amputation of his left arm at the level of the upper arm. The other two patients had their arms caught in conveyer belts. All patients survived. Closure of the defect was performed acutely using a local pedicled musculocutaneous flap in one case and free vascularized musculocutaneous flaps from the amputated limbs in the two other cases. PMID- 1942158 TI - The removal of intravascular bullets by interventional radiology: the prevention of central migration by balloon occlusion--case report. AB - A migratory intravascular bullet fragment located within the hypogastric vein was removed successfully with the aid of interventional radiologic techniques. The authors describe the use of the technique of balloon trapping as part of this procedure. A balloon should be inflated between the foreign body and the heart before retrieval is attempted in order to prevent migration back to the heart during the manipulation. PMID- 1942159 TI - Peripheral arterial shotgun missile emboli: diagnostic and therapeutic management -case reports. AB - Arterial bullet embolism is an uncommon complication of vascular trauma. While many reports exist of peripheral embolism from aortic entry sites, few cases are described of distal embolization from peripheral arteries. Untreated emboli may cause ischemia and threaten the limb at a site far removed from the point of missile entry. Unless suspected, diagnosed, and extracted, these emboli may ultimately result in limb loss in spite of a successful proximal arterial repair. During the last 10 years we treated 4 such cases, all of whom had initial limb salvage. This report describes our diagnostic and operative management of these injuries and collectively summarizes our experience as well as all other cases in the literature. PMID- 1942160 TI - Hand infections secondary to catfish spines: case reports and literature review. AB - Catfish are one of the few freshwater fishes known to be venomous. Although "finning" of the hand is a frequent injury incurred by catfish anglers that results in intense pain, it rarely results in any long-term sequelae. We present three cases in which acute soft-tissue infections developed, necessitating ray amputations in two patients. The unique habitat and anatomy of the catfish are described and preventive and therapeutic measures are discussed. PMID- 1942161 TI - Collet-Sicard syndrome resulting from closed head injury: case report. AB - A 67-year-old man developed paralysis of the right ninth, tenth, eleventh, and twelfth cranial nerves (Collet-Sicard syndrome) after sustaining a closed head injury. Plain x-ray films of the skull revealed two linear fractures of the occipital bone (one of them probably traversing through the right occipital condyle) and a prominent soft-tissue shadow in the region of the nasopharynx, suggestive of a skull base fracture. The patient was managed conservatively. This is the only case of unilateral multiple caudal cranial nerve palsies (IX through XII), seen by us over a 20-year period, from among more than 5,000 moderate to significant head injuries. PMID- 1942162 TI - Long bone fracture in a spinal-cord-injured patient: complication of treatment--a case report and review of the literature. AB - Long bone fractures in patients with spinal cord injuries are difficult to manage. A case is presented in which complications arose after a femur fracture in a paraplegic patient was treated by closed fixation in a long leg circular plaster cast and the literature on management of long bone fractures in patients with spinal cord injuries is reviewed. PMID- 1942163 TI - Central fracture-dislocation of the hip with ipsilateral femoral neck fracture: case report. AB - Central fracture dislocation of the hip with associated fracture of the femoral neck is rare. Treatment of choice consists of open reduction of the displacement and internal fixation of both fractures. Nevertheless, inadequate reduction of the burst fracture of the acetabulum may lead to hip arthritis, and the surgical approach to the femoral neck jeopardizes its vitality. In elderly patients early full motion and prompt physical rehabilitation can be achieved by total hip arthroplasty after fusion of the displaced femoral head to the acetabular wall. PMID- 1942164 TI - Tear of the cervical esophagus following hyperextension from manual traction: case report. AB - Cervical esophageal disruption is a known complication of hyperextension injuries of the cervical spine. A patient was seen at our institution after nonprofessional manipulation of the cervical spine. There was no apparent cervical spine injury. Following diagnosis, the neck was explored and the esophageal tear repaired and drained. The patient recovered uneventfully. PMID- 1942165 TI - Irreducible dorsal dislocation of the small finger distal interphalangeal joint: the importance of roentgenograms--case report. AB - Irreducible dorsal dislocations of the distal interphalangeal joints of the fingers are uncommon injuries. They are almost always the result of an athletic injury. Although usually open, these can be subtle, closed injuries. Proper diagnosis requires clinical awareness and mandatory roentgenograms of all interphalangeal joint injuries. PMID- 1942166 TI - The influence of substrate background on the acute metabolic response to epinephrine and cortisol. AB - The acute metabolic effects of epinephrine and cortisol, as well as the influence of substrate background on the effects of these two hormones were investigated in normal subjects. While receiving a hypocaloric dextrose feeding (50 ng/kg/h) (DEX), the subjects received a 6-hour continuous intravenous infusion of epinephrine (30 ng/kg-min) (EPI), followed by a 6-hour infusion of a combination of epinephrine (30 mg/kg-min) and cortisol (3.0 microgram/kg-min) (EC). The hormone infusion was repeated 1 week after a continuous intravenous feeding regimen (TPN) was begun with a caloric content of 1.5 times the measured metabolic rate. Under both DEX and TPN, EPI produced increased energy expenditure, hyperglycemia, hyperlactic acidemia, and hypoaminoacidemia. Except for a further increase in circulating glucose levels during the DEX condition, these variables were not altered by the addition of cortisol. Epinephrine under both feeding conditions increased lactate efflux from the extremity without changes in peripheral oxygen or glucose uptake. The hypoaminoacidemic response to EPI in the DEX condition was associated with a decrease in extremity efflux of amino acids (-654 +/- 89 nmol/min/100 cm3 tissue at baseline vs -330 +/- 86 nmol/min/100 cm3 for EPI, p less than 0.05). No change in extremity amino acid flux was noted in response to EPI during total parenteral nutrition. Even with addition of cortisol no significant efflux of amino acids above baseline levels was noted in either feeding condition. We therefore conclude that (1) total parenteral nutrition cannot abolish the hypermetabolic or hyperglycemic response to epinephrine and cortisol; (2) increased extremity lactate efflux and lactic acidosis can occur in response to epinephrine without evidence of diminished oxygen delivery to the extremity; and (3) these two hormones are not primary mediators of acute extremity nitrogen loss. PMID- 1942167 TI - The morphology of smoke inhalation injury in sheep. AB - Pulmonary injury resulting from inhalation of chemical and particulate products of incomplete combustion is one of the principal determinants of mortality following burn injury. In this study, the histopathology of inhalation injury was examined in sheep. Mild, moderate, or severe smoke injury was produced in anesthetized sheep by insufflation with various doses of ambient temperature smoke, generated by burning polyethylene, wood pulp, and nonwoven cellulose pads. A total of 64 sheep were exposed and evaluated at times ranging from 15 minutes to 4 weeks after exposure. Morphologic changes in the lungs were studied using light microscopy and both transmission and scanning electron microscopy. The primary, dose-responsive injury observed was acute cell membrane damage in the trachea and bronchi leading to edema, progressive necrotic tracheobronchitis with pseudomembrane formation, and airway obstruction. These inflammatory and occlusive effects were followed by congestion, alveolar space edema, atelectasis, and bronchopneumonia. Morphologic changes occurring in the alveolar epithelium following high smoke dosage included intracellular edema in type-I cells, changes in the membrane-bound vacuoles of type-II cells, and septal thickening caused by interstitial edema. No capillary endothelial changes were observed. PMID- 1942168 TI - Intraosseous transfusion in an anesthetized swine model using 51Cr-labeled autologous red blood cells. AB - Peripheral venous access can often be difficult to obtain in infants and young children. Landmark articles in the 1940s showed that the intraosseous (IO) route was a viable one for resuscitation. While anecdotal reports and clinical experience suggest that blood products can be transfused via the IO route, it has not been specifically studied nor documented. We performed a prospective study to document the feasibility of red blood cell transfusion via the IO space. We studied the rapid infusion of 51Cr-labeled red blood cells via the IO space through an 18-gauge IO needle in three normovolemic immature swine. Serial central venous samples were removed at 30 seconds and at 1, 5, 15, 30, and 60 minutes and analyzed for evidence of radiolabeling. Our results revealed rapid delivery of radiolabeled red blood cells into the central circulation with no evidence of early heomolysis. Highest counts were seen in samples taken at 30 seconds to 1 minute. We conclude that the IO route is a viable means for blood transfusion in a nonhemorrhagic model. PMID- 1942169 TI - Ceftriaxone (Rocephin) in abdominal trauma. AB - A prospective study was undertaken to evaluate the use of ceftriaxone in patients with abdominal trauma admitted to our hospital over a period of 6 months. Because of the large trauma load and an unacceptable waiting period before surgery combined with the fact that many patients on 6-hourly antibiotic regimes often did not receive their second and third doses, it was decided to use ceftriaxone because of its long half-life with maintenance of fluid and tissue concentrations for 24-48 hours. Because ceftriaxone is not reliably effective against anaerobic organisms such as Bacteroides fragilis, it was decided to add metronidazole as a combined initial dose. Two hundred ninety patients were entered in this trial, of which there were 259 stab wounds (89.3%), 20 missile injuries (6.9%), and 11 blunt injuries (3.8%). It was found that the mean delay between injury and initial dosage of ceftriaxone was 9.1 hours, with a range of 1-126 hours, and the mean delay between antibiotic therapy and operation 6.3 hours, with a range of 0 39 hours. The organs most frequently injured were the small bowel, the large bowel, the stomach, and the liver. Wound infection developed in only 4 patients (1.4%); intra-abdominal sepsis did not occur; and 35 patients (12%) developed respiratory infections. There were no deaths. We conclude that ceftriaxone, because of its 24-hour dosage was not only convenient but also adequate to prevent intra-abdominal sepsis and there was no difference in cost between this product and our previous protocol of 6-hourly antibiotic regime. PMID- 1942170 TI - Ventilatory effects of medical antishock trousers in healthy volunteers. AB - The ventilatory effects of medical antishock trousers (MAST) were investigated using 10 healthy volunteers. Use of the MAST (60-80 mm Hg) decreased forced expiratory volume (-8% +/- 4%, p less than 0.01), vital capacity (-8% +/- 5%, p less than 0.01), and functional residual capacity (-12% +/- 6%, p less than 0.01) and induced a significant decrease in tidal volume (-30% +/- 17%, p less than 0.05), but minute ventilation was unmodified because of a concomitant increase in respiratory rate (+17% +/- 8%, p less than 0.001). The MAST modified the breathing pattern: the abdominal contribution to ventilation was markedly decreased (-57% +/- 22%, p less than 0.001), suggesting a decrease in the diaphragmatic contribution to ventilation. The MAST increased both the end expiratory (+131% +/- 115%, p less than 0.01) and inspiratory variation (delta Pgas: +42% +/- 40%, p less than 0.05) of gastric pressure, whereas the end expiratory and inspiratory variation of esophageal pressure remained unchanged. Because of a higher delta Pgas, the dynamic compliance of the abdominal compartment markedly fell (-77% +/- 10%, p less than 0.001). Transdiaphragmatic pressure (Pdi: +28% +/- 30%, p less than 0.05) significantly increased and the pressure-time index of the diaphragm significantly increased (+32% +/- 32%, p less than 0.05) after inflation of the MAST, suggesting an increase in the diaphragmatic cost of breathing. Inspiratory activity of the parasternal intercostal muscles significantly increased after the MAST was inflated. Computerized tomography showed that the MAST induced a cephalad shift of the diaphragm, which reduced pulmonary height.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942171 TI - Agricultural injuries in children in central Wisconsin. AB - Agriculture is widely recognized as one of the most dangerous occupations in the United States. The risk of agricultural trauma extends beyond the adult work force to include farm children. During a 2-year study of agricultural trauma conducted at the Marshfield Clinic/St. Joseph's Hospital, 246 (26.9%) of all agricultural injury victims were children (age less than 19 years). Teenagers were at greatest risk, but there were also many injuries among preschool children under the age of 6 years. Injuries occurred most often during the summer months, on weekends, and during the evening hours from 6:00 PM to 10:00 PM. There were relationships between the body part injured and the age of the child as well as between the agent associated with the injury and the age and gender of the child. Preschool farm children are particularly liable to experience head and neck trauma and injuries resulting from falls. Any successful effort to address either the prevention or treatment of agricultural trauma will need to consider that children have a unique pattern of injuries that differs from that of adults. PMID- 1942172 TI - A prospective analysis of injury severity among helmeted and nonhelmeted bicyclists involved in collisions with motor vehicles. AB - To evaluate the impact of helmet use on injury severity, patient information was prospectively obtained for all bicyclists involved in collisions with motor vehicles seen at a level-I trauma center from January 1986 to January 1989. Two hundred ninety-eight patients were evaluated; in 284 (95.3%, study group) cases there was documentation of helmet use or nonuse. One hundred sixteen patients (40.9%) wore helmets and 168 (59.1%) did not. One hundred ninety-nine patients (70.1%) had an ISS less than 15, while 85 (29.9%) were severely injured (ISS greater than 15). Only 5.2% of helmet users (6/116) had an ISS greater than 15 compared with 47.0% (79/168) of nonusers (p less than 0.0001). The mean ISS for helmet users was 3.8 compared with 18.0 for nonusers (p less than 0.0001). Mortality was higher for nonusers (10/168, 6.0%) than for helmet users (1/116, 0.9%; p less than 0.025). A striking finding was noted when the group of patients without major head injuries (246) was analyzed separately. Helmet users in this group still had a much lower mean ISS (3.6 vs. 12.9, p less than 0.001) and were much less likely to have an ISS greater than 15 (4.4% vs. 32.1%, p less than 0.0001) than were nonusers. In this group, 42 of 47 patients with an ISS greater than 15 (89.4%) were not wearing helmets. We conclude that helmet nonuse is strongly associated with severe injuries in this study population. This is true even when the patients without major head injuries are analyzed as a group; a finding to our knowledge not previously described.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942173 TI - Driving under the influence--a level-I trauma center's experience. AB - Alcohol-impaired driving is a major issue confronting today's society. New legislation is emerging to help curtail this ongoing problem. To evaluate the legislative effects in terms of outcome pertaining to injured drivers, we analyzed the records of 116 consecutive motor vehicle drivers who were admitted to our trauma center over a 16-month period. Medical reports, police reports, and drivers' abstracts were reviewed. Of the 116 drives, 61 (53%) had blood alcohol concentrations that exceeded the legal limit (blood alcohol level greater than or equal to 100 mg/dL) on arrival at the emergency department. Only four of these patients were ticketed for driving under the influence and received the mandatory suspension of their driver's license. None was convicted of this offense, which carries criminal charges and a revocation of the driver's license. Mechanisms for efficient collection of blood specimens and mandatory occurrence reporting are two recommendations that merit investigation to obviate further escape of injured, intoxicated drivers from the legal net. In addition, alcohol rehabilitation and education cannot be overlooked and should warrant strong societal support. PMID- 1942174 TI - The effect of patient age upon survival in pediatric trauma. AB - Developmental changes in the anatomy and physiology of growing children are thought to improve the survivability of older children to significant injury. The effect of age upon survival, however, is poorly defined. Data for 4,615 patients less than 15 years old from a statewide trauma center registry were analyzed. Injury and survival were characterized by Abbreviated Injury Scale (AIS, 1985 revision), Injury Severity Score (ISS), Revised Trauma Score (RTS), and probability of survival [P(s)] and Z by TRISS. Patients were separated into age groups of 0 through 4, 5 through 9, and 10 through 14 years. The survival rate for patients with a maximum AIS 3 for any region was significantly higher in the 10-14-year age group. There were no significant differences in survival rates from head, thoracic, and abdominal injuries stratified by AIS among the three age groups. Survival rates for ISS cohorts were consistently lowest in the 0-4-year age group, but differences failed to reach significance. Survival for RTS and P(s) intervals were similar for all ages. The Z statistic reached significance for all children (Z = 4.717, W = 1.049), and for each group (Z = 2.203-3.029). Corresponding values of the W statistic suggest approximately one additional unexpected survivor per 100 admitted children when compared with the Major Trauma Outcome Study. Logistic regression for patients with all data required for TRISS showed no significant effect for any of the three age groups. We conclude that for this patient set, survival after childhood injury is independent of the age groups used in this study, after controlling for injury severity. PMID- 1942175 TI - Radiographic assessment of blunt renal trauma. AB - Recent reports in the urologic literature suggest that radiographic evaluation of normotensive blunt trauma patients with microscopic hematuria is no longer necessary. Several facilities, however, including the Los Angeles County University of Southern California Medical Center continue to routinely perform intravenous pyelography in this setting. To further evaluate whether this practice is indicated, we retrospectively reviewed the records of 337 patients seen at our facility between May, 1986 and December, 1989 following blunt trauma with resultant microscopic hematuria but no shock. All patients were radiographically assessed with an intravenous pyelogram. Of the 337 studies, 30 (9%) had an abnormal result, including 28 renal contusions, 1 ureteropelvic junction (UPJ) disruption, and 1 non-functioning kidney (which on further evaluation revealed a congenitally absent kidney). A total of 1 significant urologic injury was identified. Thus, only one injury (0.3%) would have been missed if a policy of observation was followed in this group of patients. Our data support other reports in the urologic literature that radiographic staging is not necessary in managing blunt trauma patients with microscopic hematuria but no shock. PMID- 1942176 TI - Spinal cord injury outcomes in a population-based sample. AB - Outcomes and follow-up data from a population-based sample of 358 persons with spinal cord injuries are described. The case fatality rate during hospitalization was less than 4%. Among those who survived, over half exhibited neurologic preservation below the level of vertebral injury at onset. Twenty-four percent of those with thoracolumbar injuries and 36% with cervical injuries experienced additional later neurologic recovery. Ninety-five percent of all survivors were discharged home, and at 2 years post-injury, 48% reported no significant medical or psychosocial problems. Of a subgroup, surveyed, 63% rated their adjustment and 60% rated their quality of life as good or excellent. Overall, the favorable outcome findings of this study support a relatively positive outlook following traumatic spinal cord injury. PMID- 1942177 TI - The incidence of recurrent penetrating trauma in an urban trauma center. AB - In spite of the fact that penetrating trauma is an increasingly frequent cause of death and disability in America, little epidemiologic information is available on the recurrence rate or natural history of patients sustaining such injuries. The current study therefore was carried out to determine the recurrence rate of penetrating trauma in our institution. During the 12-month study period (August 1984 through July 1985), 556 (2%) of the 26,728 patients examined in our surgical emergency department had sustained penetrating trauma. After excluding patients who died at the time of their original injury and patients whose records were incomplete, 389 (70%) of the 556 patients were available for analysis. As of January 1990, 127 (32.6%) of the 389 patients had sustained two or more documented episodes of penetrating trauma. The incidence of recurrent penetrating trauma in the patients treated and released from the emergency department (35%) was similar to that of the patients requiring admission for their index injuries (31%). Based on the fact that the incidence of recurrent trauma was highest in men (p less than 0.01), blacks (p less than 0.01), and the uninsured (p = 0.03), it appears that recurrent penetrating trauma is a major societal as well as a medical problem. PMID- 1942178 TI - Displaced acetabular fractures: long-term follow-up. AB - From 1980 to 1987, 136 patients with displaced acetabular fractures were reviewed to compare the long-term results of operative versus nonoperative treatment. Of 90 patients followed up to 8 years (mean, 4 years, 9 months), 54 were treated operatively and 36 nonoperatively. Experience in pelvic trauma surgery was of significance both in choice of treatment and success in achieving optimum results. Assessment by a new acetabular fracture score showed that anatomic or near-anatomic restoration of the joint led to 86% excellent or good results compared with 30% good results for fractures remaining moderately or severely displaced. PMID- 1942179 TI - Otitis media in adult trauma patients: incidence and clinical significance. AB - To determine the incidence and clinical significance of otitis media in traumatized adults requiring intubation, 67 adult trauma patients admitted to a level-I trauma center over a 6-month period who required three or more days of intubation were examined otoscopically for the presence of otitis media. Eleven of these intubated brain-injured patients had otitis and upon examination all were found to have purulent paranasal sinusitis as well. In conclusion, all intubated patients with severe head injuries should be evaluated otoscopically for the presence of otitis and those patients with otitis should be examined for the presence of sinusitis. PMID- 1942180 TI - Brachial plexus injury: association with subclavian and axillary vascular trauma. AB - Proximal upper extremity (subclavian and axillary) vascular injury (SAVI) and brachial plexus injury (BPI) occur uncommonly. However, BPI may be associated with SAVI and frequently is an important determinant of long-term disability. The medical records of patients with traumatic SAVI, BPI, or both over a 5-year period were reviewed. A total of 31 patients were identified. The group was predominantly male (28 men/3 women) with a mean age of 30.5 +/- 1.8 years (range, 15-63 years). Blunt trauma accounted for 43.5% of SAVI cases and 77.8% of BPI cases. Thirteen patients (41.9%) sustained SAVI alone (group I), 10 patients (32.2%) had combined SAVI and BPI (group II), and 8 patients (25.9%) had BPI alone (group III). Subclavian and axilliary vascular injury occurred in 10 of 18 patients (55.6%) with a BPI. Brachial plexus injury occurred in 10 of 23 patients (43.5%) with a SAVI. Patients with SAVI from blunt trauma were significantly more likely to have an associated complete BPI than patients with penetrating trauma. All patients with a complete BPI (6 patients) had an associated SAVI regardless of mechanism of injury. Only one patient with a partial BPI from blunt trauma had an associated SAVI. The Injury Severity Score was significantly higher for patients in group II. An average of 2.8 and 3.3 associated injuries were observed in patients with SAVI (groups I and II) versus patients without SAVI (group III), respectively. No patient who had a complete BPI showed an improvement in neurologic status during a mean follow-up of 7.2 months. No late vascular sequelae occurred in group-III patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942181 TI - Closed depressed skull fracture in childhood reduced with suction cup method: case report. AB - A closed depressed skull fracture in a child was reduced with a suction cup. This method keeps the fracture closed and leaves no scar. PMID- 1942182 TI - Malgaigne's fracture: the Larrey variant--a case report. AB - A rare Malgaigne fracture with caudal displacement of the acetabular section is presented. This variant has not received significant mention in existing literature. It is important because it changes the approach to initial stabilization. Treatment is best accomplished with ORIF and placement of a sacral bar. Significant complications would occur if this variant were mistaken and treated with traction. PMID- 1942183 TI - Repair of a traumatic noncircumferential hepatic bile duct defect using a vein patch: case report. AB - Injury to the bile ducts secondary to blunt trauma is a rare but potentially fatal condition that presents a difficult diagnostic and treatment challenge. Various treatment options exist for repair. Vein patch repairs have been criticized because of reports of subsequent fibrosis and stricture formation. This case report describes the successful repair of a traumatic, noncircumferential defect of a hepatic bile duct with a vein patch, and stresses the importance of an adequate duration of stenting. PMID- 1942184 TI - The residual central venous catheter track--an occult source of lethal air embolism: case report. AB - Air embolization through a residual track after removal of a central venous catheter is an elusive mechanism of a treacherous problem. Prompt diagnosis is necessary for successful application of established therapy, as demonstrated by this case report. Awareness of this unusual mechanism of air embolism with utilization of simple prophylactic measures, however, remains the best treatment. PMID- 1942185 TI - Splenic injury from gunshot wounds to the chest without diaphragmatic or peritoneal violation: case reports. AB - Three cases of isolated splenic injury without peritoneal penetration are described. Two patients were explored because of bullet trajectory, one was explored because of a positive physical examination. Two patients had minor splenic injuries. One required splenorrhaphy. A review of intraperitoneal injury from extraperitoneal gunshot wounds is presented. PMID- 1942186 TI - Delayed pericardial tamponade in penetrating chest trauma: case report. AB - Penetrating wounds to the anterior chest are often associated with cardiac tamponade. If these injuries are not evaluated or treated, delayed cardiac tamponade may develop. A case report and a review of the literature are presented. PMID- 1942187 TI - Multiple vessel injury to branches of the aortic arch: case report. AB - A case of multiple injuries to the branches of the aortic arch following blunt trauma is reported. Prompt diagnosis and early operation resulted in a favorable outcome. PMID- 1942188 TI - Emergency repair of main stem bronchus disruption complicated by anastomotic stenosis: two cases of successful repair by resection and reanastomosis. AB - The case reports of two patients who developed complete bronchial stenosis after emergency repair of a left stem bronchus disruption are reported. Resection of the stenotic bronchus and reanastomosis restored a normal lung function in both patients. Arguments for a conservative approach, perioperative investigations, and technical data are discussed. PMID- 1942189 TI - Dissecting thoracic aneurysm. PMID- 1942190 TI - AIDS: immunologic abnormalities following human immunodeficiency virus infection. AB - Following human immunodeficiency virus (HIV) infection, there is an ordered progression of immunologic abnormalities that results from the selective infection of the T4 helper/inducer subset of T lymphocytes. The loss of helper T cell function disrupts both the cellular and humoral aspects of the immune response. The T lymphocytes decrease in both number and function. The peripheral blood B lymphocytes demonstrate marked polyclonal activation and are unable to mount a serologic response to new antigens. The infected monocytes and macrophages serve as reservoirs for HIV and act as vehicles that transport the virus to target organs. Decreased activity of natural killer cells may promote progression of acquired immunodeficiency syndrome (AIDS). Factors that suppress the reaction of T and B lymphocytes to stimuli have been identified in the sera of AIDS patients. In conclusion, HIV infection causes progressive dysfunction and destruction of the entire immune system, resulting in severe opportunistic infections, neoplasms, and shortened survival of AIDS patients. PMID- 1942191 TI - Thoracic manifestations of AIDS. A symposium. PMID- 1942192 TI - Transmission of HIV in health care workers. AB - Health care workers may be occupationally exposed to human immunodeficiency virus (HIV). The risk of infection is highest with accidental needlestick and similar percutaneous exposures. Emphasis should be placed on avoiding this type of accident. Strategies to prevent accidents and to manage exposures once they have occurred should be developed in each work environment. It is to be hoped that a combination of better infection control, safer devices and technologies, and postexposure prophylaxis with zidovudine (AZT) or other chemotherapeutic agents will help prevent infection in health care providers caring for HIV-infected patients. PMID- 1942193 TI - Pneumocystis carinii pneumonia. AB - Pneumocystis carinii pneumonia (PCP) is the most common index diagnosis in patients with acquired immunodeficiency syndrome (AIDS). Eighty percent of AIDS patients will eventually develop PCP. Common presenting symptoms are shortness of breath, cough, weight loss, and fever. The chest radiograph typically reveals a diffuse, bilateral, symmetric, fine-to-medium reticulonodular pattern of opacities. Upper lobe disease has been reported recently in patients who have undergone prophylactic therapy with aerosolized pentamidine. Pneumatoceles, or thin-walled air-containing cysts, have been noted in 10% of patients with PCP. Lymphadenopathy and pleural effusion are extremely rare. Therapy with various agents is generally successful, resulting in clinical and radiographic improvement within 7 to 10 days. Recurrence of PCP is common. PMID- 1942194 TI - Mycobacterial disease in AIDS. AB - An increase in tuberculosis cases in the United States has been partially linked to the large number of patients with acquired immunodeficiency syndrome. Symptoms are indistinguishable from those of other opportunistic infections and include cough, low-grade fever, and weight loss. In patients with early human immunodeficiency virus (HIV) infection, radiographic findings resemble those seen in patients with reactivation tuberculosis. In patients with advanced HIV infection, chest radiographs typically reveal bilateral, symmetric, coarse, nodular densities. An upper lobe distribution is not prevalent. Lymphadenopathy is reported in many patients. Antituberculous therapy leads to clinical and radiographic improvement. Radiographic deterioration during therapy should suggest the presence of another opportunistic infection. Mycobacterium avium complex (MAC) infection of the lung cannot be distinguished from tuberculosis clinically or radiographically. Therapy, however, is less likely to be successful in patients with MAC infection. PMID- 1942195 TI - Fungal disease in HIV-infected persons: cryptococcosis, histoplasmosis, and coccidioidomycosis. AB - The AIDS epidemic has profoundly influenced the expression of deep-seated fungal disease in this country over the past 10 years. Previously an uncommon etiology of life threatening disease, deep-seated fungal infections with Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis accounted for nearly 3000 AIDS index diagnoses in 1990. As the epidemic matures, symptomatic HIV infection can be expected to rise in areas of endemic fungal infection resulting in further recognition of systemic fungal disease. Although amphotericin B and 5 flucytosine remain the initial treatments of choice for AIDS-associated deep fungal infection, clinical trials evaluating the new triazoles offer hope for more effective prophylaxis and treatment in the future. PMID- 1942196 TI - Pyogenic bacterial pneumonia in the acquired immunodeficiency syndrome. AB - Individuals with human immunodeficiency virus (HIV) infection are more susceptible to bacterial infections because of defects in both cellular and humoral immunity. The most common causes of community-acquired pyogenic bacterial pneumonia in HIV-infected patients are Streptococcus pneumoniae and Haemophilus influenzae. The clinical presentation of HIV-infected patients with pyogenic pneumonia does not seem to differ significantly from that of patients without HIV infection. Response to therapy is generally good, and complications relatively few. Prevention of bacterial pneumonia is very important in the care of HIV infected persons. The pneumococcal vaccine is currently recommended for all HIV seropositive individuals, although its efficacy is unknown is this setting. Other forms of prevention require further investigation but may prove to be helpful. PMID- 1942197 TI - Kaposi's sarcoma. AB - An aggressive form of Kaposi's sarcoma has been reported in patients with acquired immunodeficiency syndrome. Although pulmonary symptoms may constitute the initial complaint, Kaposi's sarcoma is generally detected because of cutaneous lesions. The chest radiograph reveals a distinctive, poorly marginated, nodular pattern in the lungs. Coarse, linear densities are also observed, and pleural effusion is seen in many patients. Bilateral distribution is most common. Pulmonary hemorrhage occurs and rarely may result in dense air-space consolidation seen on the chest radiograph. PMID- 1942198 TI - Non-Hodgkin's lymphoma in the acquired immunodeficiency syndrome. AB - AIDS-related lymphomas (ARLs) are almost always of a non-Hodgkin's type. Typically, intraabdominal or subcutaneous lymph node groups are affected. Unusual presentations are not uncommon, however. Intrathoracic involvement occurs in 10% to 30% of AIDS patients. ARLs are extremely aggressive and generally present at advanced stages of disease. The chest radiograph demonstrates linear densities, lymphadenopathy, and pleural effusions. An unusual feature of ARLs is the presence of rapidly growing, well-defined lung nodules. Radiographic response to therapy may be extremely rapid, but the prognosis for patients with ARLs is poor. PMID- 1942199 TI - Noninfectious and nonmalignant pulmonary disease in AIDS. AB - Infectious and malignant disease processes are responsible for most pulmonary abnormalities seen in patients with acquired immunodeficiency syndrome (AIDS). There are, however, a number of noninfectious and nonmalignant disorders that can involve the lungs of these individuals. Nonspecific interstitial pneumonitis and lymphocytic interstitial pneumonitis may mimic opportunistic infections both clinically and radiographically. Congestive cardiomyopathy may develop and result in pulmonary edema. Other disorders such as alveolar proteinosis and desquamative interstitial pneumonitis are also reported. Bronchoalveolar lavage, a diagnostic technique frequently employed in AIDS patients, may itself produce pulmonary opacities. Knowledge of these disorders may aid in the evaluation of AIDS patients for whom an infectious etiology for pulmonary abnormalities cannot be found. PMID- 1942200 TI - The management of early human immunodeficiency virus infection. AB - The outcome of treatment in patients with early asymptomatic HIV disease has recently improved. Clinical trials with zidovudine have demonstrated efficacy and greatly reduced toxicity when the drug is used in asymptomatic HIV-infected persons who have fewer than 500 CD4+ cells/mm3, and resistance to this drug in these patients is less frequent and severe. Also, the optimum dosage of zidovudine is less than previously believed, probably in the range of 500-600 mg daily given in oral divided doses. The use of antibiotics to prevent Pneumocystis carinii pneumonia is also of clear value in HIV-infected asymptomatic or symptomatic persons with fewer than 200 CD4+ cells/mm3. Oral regimens such as trimethoprim/sulfamethoxazole or dapsone alone appear to be effective and are gaining preference over aerosolized pentamidine that is considerably more expensive. Together these medical advances argue for the encouragement of voluntary HIV testing to enable early diagnosis and, hence, optimum medical monitoring and appropriate intervention. These issues and recommendations for laboratory and clinical monitoring will be provided in this review. PMID- 1942201 TI - Pulmonary disease in children with AIDS. AB - Children with acquired immunodeficiency syndrome (AIDS) may present with recurrent pneumonias or chronic debilitating illness. The chest radiographs of these patients demonstrate homogeneous densities representing staphylococcal or other pyogenic infections. Pneumocystis carinii pneumonia produces a diffuse, symmetric, fine-to-medium, reticulonodular pattern. Lymphocytic interstitial pneumonitis, a disease that is now an index diagnosis of AIDS in children under 13, may appear as a chronic, diffuse, small nodular infiltrate. An increasing number of pediatric AIDS patients will be observed in the future because of the large number of human immunodeficiency virus-infected women who are of childbearing age. PMID- 1942202 TI - Image-guided catheter drainage of the infected pleural space. AB - Thoracic empyema occurs at all ages and has reported mortality rates of 10% to 75%. Most authors agree that complete drainage of complicated effusions or organized empyemas and reexpansion of atelectatic lung are important in obtaining a satisfactory clinical outcome. For initial tube drainage, a 26-F to 36-F chest tube traditionally has been inserted at the bedside. The results of this method of empyema evacuation have varied widely, with an overall cure rate reported to be 47%. Image-guided placement of smaller 8-F to 14-F catheters has been offered as an alternative therapy with an overall reported cure rate of 81% in 104 patients. PMID- 1942204 TI - Imaging of the expanded polytetrafluoroethylene prosthetic diaphragm following extrapleural pneumonectomy for mesothelioma. AB - Extrapleural pneumonectomy, which usually requires placement of a prosthetic hemidiaphragm, can be offered to approximately 24% of patients with malignant mesothelioma. Expanded polytetrafluoroethylene (Gore-Tex) has superior physical characteristics for diaphragmatic grafting and is the material of choice at the authors' institutions. This article describes conventional radiography and computed tomography findings in three patients who underwent extrapleural pneumonectomy. A freshly placed Gore-Tex prosthetic diaphragm appears as a radiolucent crescent-shaped band at the inferior border of the hemithorax and could be confused with a pneumoperitoneum. With time, the lucent crescent becomes thinner and eventually becomes radiopaque; it may be confused with a calcified diaphragm. PMID- 1942203 TI - Evolution of pulmonary pseudolymphomas: clinical and radiologic manifestations. AB - Solitary or multifocal pulmonary pseudolymphoma developed in two men and two women between 59 and 76 years of age. The lesions were detected incidentally in three patients and following a respiratory infection in the fourth. Follow-up radiographs and chest CT revealed gradual expansion of the opacities without cavitation, calcification, or pleural involvement. Histopathologic sections from open lung biopsies or resected segments showed dense alveolar and peribronchial infiltration by numerous mature lymphocytes and plasma cells surrounding reactive lymphoid follicles with true germinal centers. Their benign nature was confirmed by immunofluorescent studies showing polyclonal cell populations. No recurrence or malignant change occurred during 4- to 9-year periods of observation. The clinical and radiologic features of pulmonary pseudolymphoma are presented with a brief review of 54 previously reported cases. PMID- 1942205 TI - Right ventricular perforation: a rare complication of percutaneous lung biopsy. AB - A 6 mm tear developed in the right ventricle as a complication of a percutaneous lung biopsy. The main causative factor was operator inexperience. A low platelet count may have contributed to the hemopericardium. PMID- 1942206 TI - A five-year prospective study of septicaemia in hospitalized children in Hong Kong. AB - In a 5-year prospective study in a Hong Kong teaching hospital there were 344 clinically significant episodes of paediatric septicaemia. Many of the microbiological and clinical features were similar to those reported in Japanese and Western studies but there were some important differences. Half of the episodes (or 70% if neonatal infections are excluded) were community-acquired. The commonest organisms found were Salmonella spp (15% of all and 27% of community-acquired infections); this was related to the high local incidence of salmonellosis and typhoid fever. Salmonella typhi, which was responsible for one third of the salmonella septicaemias, was usually seen in school-age children, while non-typhoid salmonellae were common in infants. Methicillin-resistant Staphylococcus aureus, which are now endemic in Hong Kong hospitals, was a common cause of hospital-acquired septicaemia. Pneumococcal septicaemia accounted for 22% of episodes in infants and pre-school children, but Haemophilus influenzae was uncommon (2% of all episodes) and there was no case of meningococcal septicaemia. The rarity of invasive infection with H. influenzae and Neisseria meningitidis in Hong Kong children is unexplained. PMID- 1942207 TI - Seroepidemiology of spotted fever group rickettsial infections in humans in Zimbabwe. AB - In sera collected throughout Zimbabwe the prevalence of antibodies reactive with Rickettsia conorii (Kenya) and a Zimbabwean spotted fever group rickettsia (ZSFR) was investigated using an indirect immunofluorescence assay (IFA). A random sample of these sera was also tested using a commercial IFA test. There was close agreement between IFA titres using the African rickettsial antigens and the commercial antigen slides. When differences in titre were detected, these were rarely greater than a twofold serum dilution. In Western blot immunoassays, IFA positive human sera detected immunogens of ZSFR and R. conorii (Kenya) that could also be demonstrated with homologous mouse antisera. The overall seroprevalence was 52% to R. conorii (Kenya) and 55% to ZSFR. For both antigens the highest seroprevalence was recorded from the south of the country, where the highest incidence of clinical tick-bite fever was reported in a questionnaire survey to medical practitioners. No difference was found between the seroprevalence in males and females, but high titres of antibody were common in samples from young people. PMID- 1942208 TI - Gelatinous transformation of the bone marrow and Leishmania donovani infection. AB - To the best of our knowledge, gelatinous transformation of the marrow has not been described in association with Leishmania donovani infection. Here we report one such case. PMID- 1942210 TI - Glucose-6-phosphate dehydrogenase deficiency in a rural Saudi population. AB - 3291 Saudi male blood donors from a non-malarial area of Saudi Arabia were investigated for their glucose-6-phosphate dehydrogenase levels. The prevalence of glucose-6-phosphate dehydrogenase deficiency in the Al-Kharj area was 1.91% which is one of the lowest recorded in Saudi Arabia. PMID- 1942209 TI - Ability of Anopheles gambiae mosquitoes to transmit malaria during the dry and wet seasons in an area of irrigated rice cultivation in The Gambia. AB - The seasonality of malaria transmission was studied in a Gambian village situated in an area where rice was cultivated. Observations were made during two dry seasons, when pump-fed irrigation was used to grow rice, and in the intervening rainy season, when rice was cultivated using a combination of irrigated and rain fed paddies. Clinical episodes of malaria were mainly confined to the months during and soon after the rainy season. In the wet season the prevalence of parasitaemia was higher in febrile subjects than in afebrile controls but the reverse applied during the dry seasons. However, the biting rates of Anopheles gambiae complex mosquitoes in the two dry seasons (2.5 and 0.8 bites/child/night respectively) were greater than or similar to that in the rainy season (0.6 bites/child/night). The proportion of human bloodmeals (0.53 vs 0.75) and the survival of mosquitoes (parity rates of 0.41 vs 0.58) were both lower in the dry seasons than in the rains. The low prevalence of morbidity due to malaria in the dry season and the observed fall in the sporozoite rate may therefore have been due to a reduction in the vectorial capacity of the An. gambiae population. However, reduced transmission in the dry season may also have been due to the direct effect of high temperatures on the parasite in the vector. PMID- 1942211 TI - Sero-epidemiology of toxoplasmosis in Gezira, Sudan. AB - 386 blood samples from residents of Gezira Province, Sudan were tested by a latex agglutination test for toxoplasmosis. 41.7% of the sample were found positive with antibody titres of greater than or equal to 1/64. Females aged 20-49 years had a significantly higher prevalence rate than males of the same age. No correlation was found between seropositivity and history of contact with domestic cats or between seropositivity and rural versus urban residence. The findings of this study and the known food habits of the study population suggest ingestion of Toxoplasma cysts in meat to be the main mode of transmission of the disease. PMID- 1942212 TI - Human fascioliasis in Egypt: effect of infection and efficacy of bithionol treatment. AB - The present study was conducted on 14 patients with established fascioliasis. The effect of infection on the haematological and biochemical parameters was determined and the liver and gall bladder were studied by ultrasonography. Bithionol was given in the dose of 30 mg kg-1 body weight every other day for 5 doses. The therapeutic efficacy was assessed by egg and eosinophilic counts and quantitative estimation of antibody titres by indirect haemagglutination test. Results revealed that fascioliasis caused normocytic hypochromic anaemia and eosinophilia. Serum bilirubin, ALT and AST were within normal range. Ultrasonography showed a normal echogenic pattern of the liver and gall bladder. One case showed thickness of the gall bladder wall which was tender under the transiducer. Fasciola eggs disappeared completely after the 5th dose giving a cure rate of 100%. Antibody titres reached a normal level at the end of the 3rd month post treatment. Bithionol proved to be a potent fasciolicidal drug with minimal side-effects. PMID- 1942213 TI - Hypothesis: the significance of Winterbottom's sign. AB - Swollen glands in the neck in African sleeping sickness is usually considered to be a sign of peripheral trypanosomiasis without cerebral involvement. Experimental evidence of connection between these glands and the ventricles of the brain is reviewed. The evidence suggests that Winterbottom's sign may indicate also a cerebral infection. It also suggests that trypanosomes may enter the brain via the lymphatic system. PMID- 1942214 TI - Clinical presentation of enteric fever: its changing pattern in Kuwait. AB - The clinical experience with enteric fever (1985-89) at a general hospital in Kuwait is presented. There were 90 cases of typhoid and 10 cases of paratyphoid fever, with a mortality rate of 2%. Typhoid complications of bowel perforation, haemorrhage or septic shock were present in 5% and abortion in 2%. Neurological or psychiatric manifestations were a feature in 15%. Most infections were imported (78%). Despite rapid economic development, enteric fever may still be acquired locally but less frequently with time. This contributed to initial diagnostic uncertainty in 18% of cases, and especially in children. Another changing pattern emerged with the recent finding of five drug-resistant Salmonella typhi isolates, two in 1988 and three in 1989. Efforts are clearly needed to diagnose enteric fever more rapidly and to utilize new antibiotics for drug-resistant cases. PMID- 1942215 TI - Schistosoma mansoni eggs in urine. AB - S. mansoni eggs show a preferential localization in stools with localization in urine being unusual. The factors that influence the appearance of S. mansoni in urine have not been studied extensively. The data presented here were collected during a schistosomiasis survey conducted in the northern provinces of Cameroon and a longitudinal community survey in Douloumi. As expected, the majority of individuals infected with S. mansoni had eggs in their stools. However, this is not always the case. Under special epidemiologic conditions, very high S. haematobium prevalence and much lower S. mansoni prevalence, urinary localization may become dominant. Individuals with high intensities of infection by S. mansoni do not have a higher probability for having S. mansoni in urine (there is no 'spill over'). PMID- 1942216 TI - Typhoid fever in Singapore: a review of 370 cases. AB - The medical records of 370 patients treated for typhoid fever between 1986 and 1988 at the Communicable Disease Centre, Singapore, were reviewed. The disease was generally mild. There was no mortality. Fever was found in 98.4% of patients on admission and diarrhoea in 21%. Cough was predominantly a symptom of children and occurred in 7.1% of patients aged below 15 years. Other symptoms were uncommon. Hepatomegaly was found in 71% and splenomegaly in 47%. Leucopenia was not a helpful diagnostic marker. Chloramphenicol was the drug of choice. The relapse rate was 5.4% and the convalescent and temporary carrier rates 11.6%. The risk of developing the carrier state was significantly higher among patients who were afebrile on admission compared with those who were febrile (P less than 0.001); it was also higher in patients treated with ampicillin as compared to those treated with chloramphenicol (P less than 0.001, chi 2 = 22.7, odds ratio = 5.25, 95% confidence limits: 2.46 and 11.29). The role of ampicillin as a first line treatment for acute typhoid fever may need further re-evaluation. PMID- 1942217 TI - Faecal indicator bacteria on the hands and the effectiveness of hand-washing in Zimbabwe. AB - Two aspects of hand-washing were explored in this study. Mothers and children from 80 families in Zimbabwe were asked to wash their hands in the traditional manner in sterile water. Mothers were asked to answere a socio-economic questionnaire. By using the questionnaire and observations in conjunction with the microbiological data from hand-washing, factors were identified which contributed to high counts on the hands. These were: high relative humidity, living on a commercial farm, and having an infant in the family. Mothers and children 1-5 years of age had higher counts than children of 6-12 years. People recently involved in outdoor physical activities such as farming had higher counts than those involved in other activities. The traditional hand-washing method was also compared with two other hand-washing methods: hand-washing using soap and hand-washing using a container known as the mukombe. Hand-washing with soap was the most effective method closely followed by hand-washing using the mukombe. The least effective method was traditional hand-washing. PMID- 1942218 TI - High-resolution ultrasonography of the carpal tunnel. AB - Twenty-eight wrists of 25 patients with carpal tunnel syndrome (CTS) and 28 wrists of 14 normal control subjects were studied with high-frequency real-time ultrasonography. Three general findings could be observed in CTS, regardless of its cause: swelling of the median nerve at the entrance of the carpal tunnel; flattening of the median nerve in the distal carpal tunnel; and increased palmar flexion of the transverse carpal ligament. Quantitative analysis proved these findings to be significant. We conclude that high-resolution sonography is able to diagnose median nerve compression in the carpal tunnel syndrome and to detect some of its potential causes. PMID- 1942219 TI - Sonographic spectrum of fetal cardiac hypoplasia. AB - Four cases of hypoplastic left ventricle and three cases of hypoplastic right ventricle detected sonographically prenatally are presented. A four-chamber view of the heart was abnormal in all seven cases. The sonographic appearance of the hypoplastic ventricle was variable, being smaller than normal in six of seven cases and not being identified at all in one case. Other ultrasound findings included an atrial septal defect (n = 7); increased size of the contralateral ventricle (n = 6); nonvisualization or poor visualization of the outflow tract of the affected ventricle (n = 6), and intact ventricular septum (n = 5). In one of four cases of hypoplastic left ventricle the pregnancy was terminated; the other three infants died within 5 days after birth. One of the three fetuses with hypoplastic right ventricle was aborted. Of the remaining two infants included one had tricuspid atresia with a ventricular septal defect and one had pulmonary atresia with an intact ventricular septum. Both infants are alive, have had palliative surgery, and will be considered for a more definitive surgical repair. An abnormal four-chamber view of the heart should alert those performing routine obstetrical ultrasound to a possible hypoplastic ventricle, so that the pregnant woman can be referred to a center capable of performing more sophisticated fetal echocardiography. PMID- 1942220 TI - Uterine synechiae in pregnancy: expanded criteria for recognition and clinical significance in 28 cases. AB - Amniotic sheets caused by preexisting uterine synechiae may be recognized in pregnancy by presence of a bulbous free edge containing a hypoechoic zone and Y shaped splitting of the sheet at the endometrial margin. The placenta is contiguous with, is indented by, or extends along the synechia in up to two third of cases. In 28 cases, amniotic sheets did not cause fetal damage, but they did lead to a significantly higher primary cesarean section rate by causing fetal malpresentation and possibly by contributing to low placental implantations and bleeding. Previous curettage had been done in 78% of these patients. PMID- 1942221 TI - How accurate is second trimester fetal dating? AB - In this study, the Hadlock models for fetal dating using single and multiple parameters were tested retrospectively in 1770 chromosomally normal singleton fetuses in the second trimester (14 to 21 weeks of fetal development). The 95% confidence interval using measurements of the fetal head and femur individually was approximately +/- 1 week, which is comparable to the results of recently published dating models from other centers designed specifically for use during this time frame. The use of multiple-parameter models results in statistically significant improvement in prediction of age, in terms of both random error and maximum observed errors. We conclude that these models, developed for dating between 14 and 42 weeks of fetal development, provide highly accurate estimates of fetal age in the second trimester of pregnancy. PMID- 1942222 TI - Assessment of ovarian tumor vascularity with transvaginal color Doppler sonography. AB - This report describes the results of transvaginal color Doppler sonography (TV CDS) of 43 surgically proved ovarian masses. Waveform analyses of the signals arising from specific vessels (i.e., peripheral, central, septal) adjacent to and within these masses were correlated to those seen on macroscopic pathologic evaluation. The mean and standard deviation of the pulsatility indices (PI) of 32 benign lesions (1.8 +/- 0.8) were higher than 11 malignant ones (0.8 +/- 0.6) (P = 0.03). However, the range of benign (4.0 to 0.7) and malignant (1.5 to 0.4) lesions did overlap. Low PIs (less than 1.0) were found in five relatively benign lesions (one case each of dermoid cyst, cystadenoma containing a dermoid cyst, endometrioma, benign sclerosing stromal tumor, and thecoma), but also in all 11 malignant or borderline malignant lesions (nine cystadenocarcinomas, two germ cell tumors), causing an overlap between the PIs of some benign and malignant masses. With a 100% negative predictive value, our preliminary data suggest that TV-CDS can effectively exclude malignancy. However, with a positive predictive value of 73%, one in four malignant lesions diagnosed by TV-CDS will be benign. PMID- 1942223 TI - Noninvasive diagnosis of cardiac allograft rejection by means of pulsed Doppler and M-mode ultrasound. AB - The changes of left ventricular (LV) diastolic function associated with cardiac rejection were evaluated. Twenty-one cardiac allograft recipients aged 41 +/- 9 years, 11 with moderate to severe and 10 allograft rejection without rejection at myocardial biopsy underwent serial echo examination, including peak velocity (PEV), pressure half-time (PHT), velocity-time integral (VTI-E) of early mitral flow, and isovolumetric relaxation period (IVRP). In transplant recipients, significantly higher values than in 22 age-matched healthy controls were found for PEV (71 versus 56 cm/s; P less than 0.01), PHT (51 versus 43 ms; P less than 0.001), VTI-E (72 versus 57 mm; P less than 0.001), and IVRP (90 versus 73 ms; P less than 0.001). During rejection, heart rate increased significantly from 78 to 91 beats per minute (P less than 0.01). Furthermore, a significant decrease was found for PEV from 73 to 63 cm/s (P less than 0.01), for PHT from 52 to 40 ms (P less than 0.001), for VTI-E from 75 to 61 mm (P less than 0.001), and for IVRP from 90 to 74 ms (P less than 0.001) during cardiac rejection. Thus, sonographic evaluation of LV diastolic function helps to early detect cardiac rejection and to decrease the frequency of myocardial biopsy. PMID- 1942224 TI - The fetal presacral pseudo-mass: a normal sonographic variant. AB - We examined 416 consecutive third trimester intrauterine gestations over a 4 month period and discovered 26 hypoechoic masses in the fetal presacral space (6.3% incidence). These masses varied in diameter from 15 to 30 mm (mean, 21.5 mm). All neonates were normal on follow-up examination, without evidence of any masses or neurologic deficits. The fetal rectosigmoid colon frequently is identified in the third trimester and may reach 2 to 3 cm at term. Because the prevalence of meconium-filled rectum (6.3%) exceeds that of a presacral teratoma (0.0025%), this normal anatomic variant should be considered the most common cause of a third trimester presacral "mass." PMID- 1942225 TI - Endoluminal gynecologic ultrasound: preliminary results. AB - Specially developed high-resolution real-time ultrasound transducers (12.5 and 20 MHz) on the tip of endoluminal catheters were inserted into the endometrial canal to evaluate the usefulness of this approach. Uterine abnormalities, most confirmed by biopsy, surgery, or both, were detected in 12 patients, including submucosal myomas, nabothian cysts, endometrial polyps, synechiae, and endometrial and cervical carcinoma. In one case the catheter was directed under hysteroscopic guidance into a fallopian tube, demonstrating its potential usefulness in this region. In 4 of the 12 cases in which a hysterectomy was performed, an in vitro ultrasound examination of the organ was performed, which confirmed the initial in vivo ultrasound impressions. Anatomic cross-sectional slices of the uterus resulted in excellent correlation with the ultrasound findings. These preliminary results suggest that this new sonographic procedure will become an important diagnostic tool, supplementing abdominal and endovaginal ultrasound approaches. PMID- 1942226 TI - Embryonal heart rate as a predictor of pregnancy outcome: a prospective analysis. AB - To evaluate the association between embryonal heart rate and pregnancy outcome, we prospectively followed 50 very early pregnancies (4.5 to 7.3 weeks of gestation) through the first trimester. Of the 11 embryos that miscarried, 6 had initial heart rates below 85 beats per minute (bpm); in contrast, none of the viable embryos had initial heart rates of or below 85 bpm (P less than 0.0001). A rise in mean heart rate was seen among the viable embryos with increasing gestational age, in concordance with previously reported rates. PMID- 1942227 TI - Arteriovenous fistula of the native kidney: diagnosis by duplex Doppler ultrasound. PMID- 1942228 TI - Megacystis-microcolon-intestinal hypoperistalsis syndrome: prenatal identification in siblings and review of the literature. PMID- 1942229 TI - Unsuspected humeral head fracture diagnosed by ultrasound. PMID- 1942230 TI - In utero sonographic appearance of the atrial septum primum and septum secundum. AB - We present our observation of the sonographic appearance of the septum primum and septum secundum. The septum primum, as the valve of the foramen ovale, has been previously described as a mobile, echogenic line or dot in the left atrium. We believe that these previous descriptions recognize only a small part of a more complex three-dimensional shape. We studied 14 ideal patients, none of whom were referred for suspected fetal cardiac disease. In 1 case the septum primum was seen as a flaplike structure and in 8 cases as a circular structure. In 5 cases it was seen as both flaplike and circular, depending on the scan plane selected. A three-dimensional description of the shape of the septum primum, based on the work of Crelin, is proposed, which explains these two appearances. A better understanding of this anatomical feature may prevent mistaking the septum primum for an abnormality and provide the basis for future advances in fetal echocardiography. PMID- 1942231 TI - Use of routine prenatal ultrasound by private practice obstetricians in Iowa. PMID- 1942232 TI - A prospective longitudinal study of growth in twin gestations compared with growth in singleton pregnancies. I. The fetal head. AB - Since the available data on growth in twin gestations have been derived from retrospective cross-sectional studies with varying results, a prospective longitudinal study was initiated to assess fetal head growth in twin gestations as compared to singleton pregnancies. In uncomplicated twin gestations, growth of the fetal head, based on the increment in growth over time and the rate of growth throughout pregnancy, was found not to be significantly different than in singleton pregnancies. In light of these findings, current nomograms derived from measurements obtained in singleton pregnancies remain useful for evaluating fetal head growth in twin gestations. PMID- 1942233 TI - A prospective longitudinal study of growth in twin gestations compared with growth in singleton pregnancies. II. The fetal limbs. AB - The assessment of fetal growth is crucial in twin gestations, since the information gained often has an impact on pregnancy management. The measurement of the fetal anatomy by ultrasound enables us to follow the growth and development of the fetus. However, the pattern of fetal growth in twin gestations has not yet been precisely characterized in prospective studies. In this light, we initiated a prospective longitudinal study and sonographically examined 35 patients with twin gestations every 3 weeks from the 15th week until delivery. Multiple biometric parameters were measured, including the femur length, humerus length, ulna length, and tibia length. The results of our study showed that growth of these long bones was not significantly different between twins A and B throughout gestation and that the growth velocity between twins and singletons was not significantly different. The incremental growth, although significantly less in twins than in singletons, was so small that it was judged not to be of clinical importance to warrant the generation of separate nomograms for the evaluation of growth in twin gestations. PMID- 1942234 TI - Ultrasound of the postpartum uterus. Prediction of retained placental tissue. AB - We reviewed ultrasound images an 53 postpartum patients referred for possible retained products of conception and correlated specific ultrasound patterns with clinical and pathologic follow-up. The most common finding in patients with retained placental tissue was an echogenic mass in the uterine cavity, seen in 9 of 11 patients with pathologically proven retained placental tissue. In the remaining 2 patients with pathologically confirmed retained placenta, a heterogeneous mass was seen in the uterine cavity at some point during the course of serial sonography. Retained placental tissue was unlikely when ultrasound demonstrated a normal uterine stripe (n = 18), endometrial fluid (n = 6), or hyperechoic foci in the uterine cavity without an associated mass (n = 17). The latter finding was often associated with recent uterine instrumentation. The sonographic appearance of retained placental tissue is variable, but detection of an echogenic mass in the uterus strongly supports the diagnosis. A heterogeneous mass is sometimes caused by retained placenta, but can also be secondary to blood clots or infected or necrotic material in the absence of placental tissue. Sonographic evaluation for retained products of conception is best done before uterine instrumentation to avoid confusion with iatrogenically introduced air. PMID- 1942235 TI - Doppler ultrasonographic evaluation of Denver (peritoneovenous) shunts in two patients with intractable ascites. PMID- 1942237 TI - Ovarian pregnancy resulting in a surviving neonate. Ultrasound findings. PMID- 1942236 TI - Sonographic appearance of a duodenal bulb lipoma with CT and MRI correlation. PMID- 1942238 TI - Sonographic diagnosis of testicular seminoma occurring 8 years after initial extragonadal seminoma. PMID- 1942239 TI - Appearance of molar pregnancy 9.5 weeks after conception. Use of transvaginal ultrasound for early diagnosis. PMID- 1942240 TI - Coexistent autosomal recessive polycystic kidney disease and UPJ obstruction. Prenatal sonographic findings. PMID- 1942241 TI - Inhibition of gp160 and CD4 maturation in U937 cells after both defective and productive infections by human immunodeficiency virus type 1. AB - Our results demonstrate that the formation of intracellular complexes between the envelope glycoprotein precursor gp160 of human immunodeficiency virus type 1 and CD4 is a major event, leading to the disappearance of CD4 at the cell surface of infected U937 cells. Using both productively and defectively infected clones of U937 cells, we assessed the effect of CD4-gp160 intracellular association on the maturation of both proteins. Pulse-chase labeling followed by sequential immunoprecipitation was used to analyze the processing of both free and associated CD4 and gp160, and the results showed that the trimming, proteolytic cleavage, and degradation of gp160 were completely abrogated after intracellular binding to CD4. Similarly, the maturation process which normally transforms 80% of CD4 to a partially endoglycosidase H-resistant species was also impaired subsequent to the formation of these complexes. A comparison of gp160 maturation either in free form or as a CD4 complex revealed that neither inefficient transport nor degradation of gp160 can account for the observed blockage of CD4 maturation. Moreover, this impairment was independent of gp120 and gp41, since a defective clone of human immunodeficiency virus type 1-infected cells, unable to cleave gp160, showed binding of CD4 and inhibition of CD4 transport and maturation with the same efficiency as occurred in productively infected cells. Expression of gp160 is thus necessary and sufficient to cause CD4 receptor down modulation for both productively and defectively infected cells. PMID- 1942242 TI - Transactivation of human immunodeficiency virus type 1 long terminal repeats by cell surface tumor necrosis factor alpha. AB - Tumor necrosis factor alpha (TNF-alpha) is expressed in secreted and cell surface (csTNF-alpha) forms by activated monocytic and T cells. In this report, we demonstrate that csTNF-alpha may predominantly regulate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) activation in the promonocytic cell line U937 and in the Epstein-Barr virus-transformed B-cell line BH1. Anti-TNF-alpha antibody suppressed both the constitutive expression of the HIV-1 LTR in BH1 cells and the expression induced by phorbol 12-myristate 13 acetate in U937 cells. This suppression was found to be mediated via csTNF-alpha. No correlation between the HIV-1 LTR activation and the secretion of TNF-alpha was evident in these cell lines. Suppression of TNF-alpha secretion by cyclosporin A or by a serine protease inhibitor did not suppress the HIV-1 LTR activation. These observations suggest a novel biological role for csTNF-alpha in the immunopathogenesis of AIDS. PMID- 1942243 TI - Plasma membrane receptors for ecotropic murine retroviruses require a limiting accessory factor. AB - A retroviral vector was used to express various amounts of the receptor (ecoR) for ecotropic host range murine retroviruses on naturally barren hamster, mink, and human cells. These cells and murine cells were then incubated for 2 h with dilutions of a helper-free ecotropic retrovirus that encodes human growth hormone, and the number of infected cells was later determined by growth hormone specific immunofluorescence. For all cells under the conditions of these studies, virus adsorption was the limiting step of infection and the cellular capacities for infection were unsaturated either at cell surfaces or at intracellular sites. Thus, infections occurred at low multiplicities of infection per cell and were directly proportional to virus and cell concentrations, and only a small percentage (ca. 5%) of the infectious virions became adsorbed from the medium during the 2-h incubations. Although increasing the adsorption by raising virus or cell concentrations results in more infections in the cultures, increasing adsorption by raising the number of ecoR above a low threshold had no effect on infections. Thus, cells with a low number of ecoR were infected as efficiently as highly adsorbing cells that contained many times more ecoR. To reconcile these results, we conclude that only a small, set number of cell surface ecoR can be functional for infection and that all excess ecoR can only bind virus into an unsalvageable pool. Therefore, retroviral receptors on single cells are functionally diverse. Our results suggest that activity of ecoR in infection requires a limiting second cellular component. PMID- 1942244 TI - Carboxyl-terminal determinants of Abelson protein important for lymphoma induction. AB - The carboxyl-terminal region of the Abelson protein is not absolutely required for Abelson virus transformation. However, Abelson virus strains encoding proteins missing portions of this region have a reduced ability to transform lymphoid cells in vitro and in vivo. One such strain, called P90A, is unique in that P90A-injected mice almost always develop tumors containing highly oncogenic variants that encode new forms of Abelson protein. In this work, we have examined the mechanism by which these variants are generated and used the variants to identify carboxyl-terminal protein sequences important for the induction of Abelson disease. Analysis of mice injected with helper-free P90A virus stocks demonstrates that the variants are generated during viral replication in vivo, probably as a consequence of error-prone reverse transcription. The sequence of the P90A viral genome reveals that a 19-base deletion is responsible for synthesis of the truncated Abelson protein. As a consequence of this mutation, 167 carboxyl-terminal amino acids normally found in the wild-type protein have been replaced by 33 amino acids derived from an alternative reading frame. Site directed mutants show that the combination of the deletion and the P90A carboxyl terminus is required for the generation of variants. Thus, the particular structure of the P90A protein, not the specific residues lost or gained, alters the transforming potential of the Abelson protein. Finally, the sequence of the variants encoding smaller Abelson proteins reveals that as few as 452 v-abl encoded amino acids are required for rapid induction of Abelson disease. PMID- 1942245 TI - Identification, cloning, and sequencing of a fragment of Amsacta moorei entomopoxvirus DNA containing the spheroidin gene and three vaccinia virus related open reading frames. AB - Entomopoxvirus virions are frequently contained within crystalline occlusion bodies, which are composed of primarily a single protein, spheroidin, which is analogous to the polyhedrin protein of baculovirus. The spheroidin gene of Amsacta moorei entomopoxvirus was identified following the microsequencing of polypeptides generated from cyanogen bromide treatment of spheroidin and the subsequent synthesis of oligonucleotide hybridization probes. DNA sequencing of a 6.8-kb region of DNA containing the spheroidin gene showed that the spheroidin protein is derived from a 3.0-kb open reading frame potentially encoding a protein of 115 kDa. Three copies of the heptanucleotide, TTTTTNT, a sequence associated with early gene transcription in the vertebrate poxviruses, and four in-frame translational termination signals were found within 60 bp upstream of the putative spheroidin gene promoter (TAAATG). The spheroidin gene promoter region contains the sequence TAAATG, which is found in many late promoters of the vertebrate poxviruses and which serves as the site of transcriptional initiation, as shown by primer extension. Primer extension experiments also showed that spheroidin gene transcripts contain 5' poly(A) sequences typical of vertebrate poxvirus late transcripts. The 92 bases upstream of the initiating TAAATG are unusually A + T rich and contain only 7 G or C residues. An analysis of open reading frames around the spheroidin gene suggests that the colinear core of "essential genes" typical of the vertebrate poxviruses is absent in A. moorei entomopoxvirus. PMID- 1942246 TI - Rapid antigenic-type replacement and DNA sequence evolution of canine parvovirus. AB - Analysis of canine parvovirus (CPV) isolates with a panel of monoclonal antibodies showed that after 1986, most viruses isolated from dogs in many parts of the United States differed antigenically from the viruses isolated prior to that date. The new antigenic type (designated CPV type 2b) has largely replaced the previous antigenic type (CPV type 2a) among virus isolates from the United States. This represents the second occurrence of a new antigenic type of this DNA virus since its emergence in 1978, as the original CPV type (CPV type 2) had previously been replaced between 1979 and 1981 by the CPV type 2a strain. DNA sequence comparisons showed that CPV types 2b and 2a differed by as few as two nonsynonymous (amino acid-changing) nucleotide substitutions in the VP-1 and VP-2 capsid protein genes. One mutation, resulting in an Asn-Asp difference at residue 426 in the VP-2 sequence, was shown by comparison with a neutralization-escape mutant selected with a non-CPV type 2b-reactive monoclonal antibody to determine the antigenic change. The mutation selected by that monoclonal antibody, a His Tyr difference in VP-2 amino acid 222, was immediately adjacent to residue 426 in the three-dimensional structure of the CPV capsid. The CPV type 2b isolates are phylogenetically closely related to the CPV type 2a isolates and are probably derived from a common ancestor. Phylogenetic analysis showed a progressive evolution away from the original CPV type. This pattern of viral evolution appears most similar to that seen in some influenza A viruses. PMID- 1942247 TI - An avian retrovirus expressing chicken pp59c-myc possesses weak transforming activity distinct from v-myc that may be modulated by adjacent normal cell neighbors. AB - We demonstrate that EF168, an avian retrovirus that expresses the chicken pp59c myc proto-oncogene, transforms quail embryo fibroblasts in vitro. An EF168 transformed quail clone, EF168-28, containing a single provirus, synthesizes several hundred copies of c-myc RNA and expresses elevated levels of the pp59c myc gene product. The EF168 provirus in EF168-28 was isolated as a molecular clone, and the nucleotide sequence of its c-myc allele was confirmed as identical to that of exons 2 and 3 of the chicken c-myc proto-oncogene. Extended infection of quail embryo fibroblast cultures with EF168 induced a number of in vitro transformation-associated parameters similar to those elicited by the oncogenic v myc-encoding retrovirus MC29, including alteration of cellular morphology, anchorage-independent growth, and induction of immortalized cell lines. Despite the fact that EF168 and MC29 shared these biological activities, further analysis revealed that EF168 initiated transformation in quail embryo fibroblasts, bone marrow, or adherent peripheral blood cultures 100- to 1,000-fold less efficiently than did MC29. Further, in contrast to MC29-induced foci, EF168 foci were smaller, morphologically diffuse, and less prominent. Analysis of newly infected cells demonstrated efficient expression of EF168 viral RNA in the absence of transformation. These differences suggest that while the pp59v-myc gene product can exert dominant transforming activity on quail embryo fibroblasts, its ability to initiate transformation is distinct from that of the pp110gag-v-myc gene product encoded by MC29 and may be suppressed by adjacent nontransformed cell neighbors. PMID- 1942248 TI - Human T-cell leukemia virus type II Rex binding and activity require an intact splice donor site and a specific RNA secondary structure. AB - The human T-cell leukemia virus type II (HTLV-II) regulatory protein Rex augments cytoplasmic levels of unspliced gag-pol mRNA by acting through a Rex-responsive element (RxRE) in the long terminal repeat. Purified Rex protein binds to long terminal repeat mRNA. Here, using an immunobinding assay to measure the binding of Rex protein to mutated RxRE RNAs, we show that efficient Rex binding requires a stem-bulge-loop RNA secondary structure (nucleotides [nt] 465 to 500) and specific sequences both within the stem-bulge (nt 470 to 476) and within a conserved upstream splice donor site (nt 449 to 455). Rex function in a transient transfection expression system correlates with Rex protein-RxRE RNA binding. The ability of HTLV-II Rex to interact directly with the HTLV-II splice donor site suggests that HTLV-II Rex may increase expression of unspliced gag-pol mRNA, in part, by inhibiting splicing. PMID- 1942249 TI - Viral persistence during the developmental phase of Coxsackievirus B1-induced murine polymyositis. AB - Mice infected with coxsackievirus B1 (CVB1) develop a chronic hindquarter muscle weakness which resembles human polymyositis. In this study, we used in situ hybridization to screen for persistent viral RNA in hamstring and quadriceps muscles from mice that displayed various degrees of clinical weakness. At 28 to 31 days postinfection, when chronic myositis is well developed but infectious virus can no longer be recovered, persistent CVB1 RNA was found in hindquarter skeletal muscle of all 12 infected animals examined. Persistent CVB1 showed a multifocal distribution within muscle and was associated with three different histopathology patterns (HPPs). These three HPPs (HPP-1, HPP-2, and HPP-3) represent potentially different stages in the mechanism of persistence. They are based on the pattern of grains, the location of hybridization signal within the muscle, and the accompanying histopathology. In HPP-1, virus persisted in nonnecrotic muscle fibers and was not directly associated with foci of inflammatory cells. HPP-2 consisted of virus contained within necrotic myocytes that were surrounded by inflammatory cells. HPP-3 was rare and showed virus inside infiltrating mononuclear cells in a region where muscle tissue had been extensively destroyed. Persistent CVB1 occurred more frequently in severely diseased animals and in tissue sections displaying intense inflammation. Moreover, HPP-2 showed a stronger association with tissue inflammation and hindquarter weakness than did HPP-1. These data demonstrate that CVB1 persists in skeletal muscle for at least 28 to 31 days postinfection and support the concept that this persistence plays a role in the development of murine polymyositis. PMID- 1942250 TI - Unusual Sp1-GC box interaction in a parvovirus promoter. AB - The P4 promoter of the parvovirus minute virus of mice contains a single degenerate GC box sequence which binds the transcription factor Sp1 with high affinity. The two promoters of murine Sp1 were affinity purified, and their interactions with the P4 promoter were examined. Several unusual features were observed. Methylation interference experiments demonstrated that Sp1 makes contacts with both DNA strands, including the central guanine as well as an adenine residue on the cytidine-rich strand of the GC box. UV photocross-linking revealed that the 95- and the 105-kDa promoters cross-link exclusively to opposite strands of the GC box. These results suggest that the phosphorylation of the 95-kDa Sp1 promoter results in a change in the way Sp1 is positioned on the P4 GC box and identifies a high-affinity GC box motif. PMID- 1942251 TI - Early signal transduction in measles virus-infected lymphocytes is unaltered, but second messengers activate virus replication. AB - In order to understand measles virus-lymphocyte interactions, we have started to analyze factors and events which regulate measles virus infection in peripheral blood mononuclear cells (PBMC). We analyzed the initiation of cell proliferation, induced by phytohemagglutinin, in infected and control PBMC by measuring intracellular free Ca2+ by using fura-2. Measles virus-infected and control PBMC responded similarly with an increase in the amount of cytosolic free Ca2+, indicating that the early activation events are not affected and are not involved in immunosuppression. The activation signals, Ca2+ and protein kinase C, induced specifically and independently by Ca ionophore A23187 or 12-O tetradecanoylphorbol-13-acetate (TPA), changed the restricted measles virus infection to a productive one. The combination of TPA and A23187 was the most potent activator of measles virus replication. TPA and A23187 operate through different activation mechanisms, and it is evident that measles virus replication depends on the activation of cellular signal pathways. Depletion of adherent cells enhanced virus replication, especially at the early stage of infection, indicating the inhibitory role of monocytes. Monocytes were strongly infected, but they supported complete measles virus replication only at a very low level, and virus replication could not be enhanced with TPA and/or A23187. PMID- 1942253 TI - Analysis of trans-acting response decoy RNA-mediated inhibition of human immunodeficiency virus type 1 transactivation. AB - Overexpression of trans-acting response element (TAR)-containing sequences (TAR decoys) in CEM SS cells renders cells resistant to human immunodeficiency type 1 (HIV-1) replication. Mutagenesis of TAR was used to investigate the molecular mechanism underlying the observed inhibition. A nucleotide change which disrupts the stem structure of TAR or sequence alterations in the loop abolish the ability of the corresponding TAR decoy RNAs to inhibit HIV replication. A compensatory mutation which restores the stem structure also restores TAR decoy RNA function. Synthesis of viral RNA is drastically reduced in cells expressing a functional TAR decoy RNA, but it is unaffected in cells expressing a mutant form of TAR decoy RNA. It is therefore concluded that overexpression of TAR-containing sequences in CEM SS cells interferes with the process of Tat-mediated transactivation of viral gene expression. However, the phenotype of several mutations suggests that TAR decoy RNA does not inhibit HIV-1 gene expression by simply sequestering Tat but rather does so by sequestering a transactivation protein complex, implying that transactivation requires the cooperative binding of both Tat and a loop-binding cellular factor(s) to TAR. Expression of wild-type or mutant forms of TAR had no discernible effects on cell viability, thus reducing concerns about using TAR decoy RNAs as part of an intracellular immunization protocol for the treatment of AIDS. PMID- 1942252 TI - DNase I-hypersensitive sites are associated with both long terminal repeats and with the intragenic enhancer of integrated human immunodeficiency virus type 1. AB - After reverse transcription and integration of the genome of human immunodeficiency virus (HIV) in a target cell, the viral DNA becomes packaged into chromatin. Regions of chromatin associated with regulatory functions in eukaryotes can generally be distinguished from the bulk of chromatin by an increased accessibility of the DNA to nucleases (nuclease-hypersensitive sites). In this report, the chromatin structure of the complete HIV-1 genome has been analyzed in three chronically infected cell lines of monocyte/macrophage and lymphoid origins. Digestion of purified nuclei from these cells with DNase I followed by restriction digestion and Southern blotting identified several DNase I-hypersensitive regions throughout the viral genome. Two constitutive sites were associated with the U3 region of the 5' long terminal repeat (LTR) in which the viral promoter and enhancer are located. An additional site in the R region of the 5' LTR was present only after activation of viral transcription by phorbol ester or tumor necrosis factor alpha. A fourth site was identified in all cell lines downstream of the 5' LTR (nucleotides [nt] 656 to 720), and the band corresponding to this site decreased in intensity upon activation of transcription. In the 3' LTR, a constitutive hypersensitive site was identified in all cell lines (nt 9322 to 9489). A major site (nt 4534 to 4733) was present only in a cell line of macrophage/monocyte origin in a region of the genome in which an intragenic enhancer was recently identified (E. Verdin, N. Becker, F. Bex, L. Droogmans, and A. Burny, Proc. Natl. Acad. Sci. USA 87:4874-4878, 1990). This study defines regions of the HIV genome associated with an open chromatin configuration and points to the potential regulatory role of these elements in the HIV life cycle. PMID- 1942254 TI - The quaternary structure, antigenicity, and aggregational behavior of the secretory core protein of human hepatitis B virus are determined by its signal sequence. AB - Human hepatitis B virus encodes a secretory core protein, referred to as the HBe protein, whose secretion is mediated by the pre-C signal sequence. Here we examined whether this sequence is important only for translocation of the HBe precursor (the precore protein) or whether it also contributes to the structural and biophysical properties of the mature HBe protein. When a truncated hepatitis B virus precore protein, lacking the basic C-terminal domain which is cleaved from the wild-type protein during its conversion into HBe, was expressed in human hepatoma cells, only a small amount of HBe-like protein was produced. This protein was slightly smaller than the wild-type HBe protein, suggesting that C terminal cleavage of the precore protein does not occur at the suggested site. When the authentic signal sequence of the precore protein (the pre-C sequence) was replaced by the unrelated signal sequence of an influenza virus hemagglutinin, not only the full-length but also the C-terminally truncated protein was expressed and secreted with high efficiency. Western blot (immunoblot) analyses with nonreducing gels and conformation-specific monoclonal antibodies revealed that the HBe protein secreted under control of the pre-C signal sequence was a monomer with HBe antigenicity, whereas the HBe-like protein secreted under control of the hemagglutinin signal sequence was a disulfide bridge-linked dimer with both HBe and HBc antigenicity. Electron microscopic examination of gradient-purified particulate core gene products showed that HBe protein secreted under control of the hemagglutinin signal sequence forms core particles, whereas HBe protein secreted under control of the pre-C sequence does not. Thus, the pre-C sequence not only mediates the secretion but also determines the structural and aggregational properties of the HBe protein. PMID- 1942255 TI - Variation in simian immunodeficiency virus env is confined to V1 and V4 during progression to simian AIDS. AB - We have monitored changes in the simian immunodeficiency virus (SIV) envelope (env) gene in two macaques which developed AIDS after inoculation with a molecular clone of SIV. As the animals progressed to AIDS, selection occurred for viruses with variation in two discrete regions (V1 and V4) but not for viruses with changes in the region of SIV env that corresponds to the immunodominant, V3 loop of human immunodeficiency virus. Within the highly variable domains, the vast majority of nucleotide changes encoded an amino acid change (98%), suggesting that these envelope variants had evolved as a result of phenotypic selection. Analysis of the biological properties of these variants, which have been selected for in the host, may be useful in defining the mechanisms underlying viral persistence and progression to simian AIDS. PMID- 1942256 TI - Rapid accumulation of measles virus leader RNA in the nucleus of infected HeLa cells and human lymphoid cells. AB - The 3' terminus of the single-stranded, negative-sense genome of the measles virus comprises a 55-nucleotide-long sequence, which is transcribed into a short, positive-sense RNA called the leader sequence. In other viral systems, this RNA has been shown to modulate host cell transcription. Here, we report the presence of measles virus leader RNA in both cytoplasmic and nuclear fractions of infected HeLa cells as well as T- and B-lymphoid cells. A sharp and rapid increase in the concentration of leader RNA in the nucleus of infected HeLa cells was also observed. The presence and accumulation of leader RNA in the nucleus of infected cells supports the hypothesis that the leader RNA plays a role in the down regulation of host cell transcription and may be responsible for the suppression of immunoglobulin synthesis by measles virus-infected B cells. Such alterations in immune responsiveness could aid in the establishment of a persistent infection by measles virus. PMID- 1942257 TI - Functional mapping of the human immunodeficiency virus type 1 Rev RNA binding domain: new insights into the domain structure of Rev and Rex. AB - Expression of human immunodeficiency virus type 1 (HIV-1) structural proteins requires the direct interaction of the viral trans-activator protein Rev with its cis-acting RNA sequence (Rev-response element [RRE]). A stretch of 14 amino acid residues of the 116-amino-acid Rev protein is sufficient to impose nucleolar localization onto a heterologous protein. Our results demonstrated that these same amino acid residues confer Rev-specific RRE binding to the heterologous human T-cell leukemia virus type I Rex protein. In addition, our results indicated that amino acids distinct from the nuclear localization signal are important for Rex-specific RRE RNA binding. PMID- 1942258 TI - A highly divergent simian immunodeficiency virus (SIVstm) recovered from stored stump-tailed macaque tissues. AB - We report here the results of molecular analysis of a simian immunodeficiency virus (designated SIVstm) which was isolated from a rhesus monkey inoculated with stored lymph node tissue of an Asian stump-tailed macaque. The latter monkey had died in 1977 during an epidemic of acquired immunodeficiency and lymphoma at the California Regional Primate Research Center (L. J. Lowenstine, N. W. Lerche, P. A. Marx, M. B. Gardner, and N. C. Pedersen, p. 174-176, in M. Girard and L. Valette, ed., Retroviruses of Human AIDS and Related Animal Viruses, 1988). Nucleotide sequence analysis of the gag and env regions indicates that SIVstm is an ancient member of the SIV/human immunodeficiency virus type 2 group; it is quite divergent from known SIVs isolated from African sooty mangabeys as well as from Asian macaques. Furthermore, of all SIV strains described to date, SIVstm is the most closely related to human immunodeficiency virus type 2. PMID- 1942260 TI - Induction of human immunodeficiency virus type 1 expression in chronically infected cells is associated primarily with a shift in RNA splicing patterns. PMID- 1942259 TI - The intragenic enhancer of human immunodeficiency virus type 1 contains functional AP-1 binding sites. AB - An intragenic enhancer in the pol gene of human immunodeficiency virus type 1 has previously been identified (Verdin et al., Proc. Natl. Acad. Sci. USA 87:4874 4878, 1990). This element is composed of two subdomains both exhibiting phorbol ester-inducible enhancing activity on the viral thymidine kinase promoter in HeLa cells. Examination of the nucleotide sequence of one of these domains (nucleotides 4079 to 4342, HXB2 isolate) revealed the presence of three short DNA regions highly homologous to the recognition site for cellular transcription factor AP-1. Two short oligonucleotides containing these AP-1 sites each functioned as a phorbol ester-inducible enhancer when cloned upstream of the thymidine kinase promoter and transfected into HeLa cells. Gel mobility shift assays and competition experiments using the same two oligonucleotides demonstrated that they bound affinity-purified AP-1 or AP-1 present in uninduced and 12-O-tetradecanoylphorbol-13-acetate-induced HeLa nuclear extracts. Footprinting experiments confirmed that all three predicted sites bound purified AP-1. These results suggest that the AP-1 factor could play a role in the transcriptional regulation of human immunodeficiency virus type 1 gene expression. PMID- 1942261 TI - Retraction. Moloney murine leukemia virus integration protein produced in yeast binds specifically to viral att sites. PMID- 1942262 TI - Transitional cell carcinoma of the prostate. PMID- 1942263 TI - Stones in horseshoe kidneys: results of treatment by extracorporeal shock wave lithotripsy and endourology. AB - We report the results of 7 patients with calculi in a horseshoe kidney treated by extracorporeal shock wave lithotripsy (ESWL, 9 renal units) and percutaneous nephrolithotripsy (3 renal units) during a 3-year period. In the ESWL only group complete stone clearance was achieved in only 3 patients (50%) after an average of 3 sessions of therapy. On the other hand, complete stone clearance was achieved by percutaneous nephrolithotripsy with minimal complications. The poorer results with ESWL were due to difficulty in ultrasonographic localization of stones as well as poor drainage in these abnormal kidneys. Our experience with the Edap LT01 and the Sonolith 2000 lithotriptors suggests that while reasonable results are possible, treatment probably will require multiple sessions and the eventual outcome is less predictable than in normal kidneys. In contrast, the treatment of complicated stones in a horseshoe kidney presents no additional difficulty. PMID- 1942264 TI - Ultrasound guided percutaneous renal biopsy using an automatic core biopsy system. AB - With real-time ultrasound visualization and an automatic core biopsy system 23 percutaneous renal biopsies were performed with the use of local anesthesia in 22 patients. Adequate tissue for diagnosis was obtained in all 23 cases, with 1 patient undergoing bilateral renal biopsy and 1 requiring repeat biopsy. One patient had an asymptomatic perirenal hematoma and 1 experienced a single episode of transient gross hematuria. There were no major complications. The use of an automatic core biopsy system guided by real-time ultrasound is an important technique that may be added to the urological armamentarium. PMID- 1942265 TI - Intraoperative renal ultrasonography: a useful adjunct to partial nephrectomy. AB - Several evolutionary changes in ultrasonographic instrumentation, including miniaturization of transducers and marked improvement in resolution, have made intraoperative renal ultrasonography a valuable adjunct for intrarenal surgery. We investigated its use in 6 patients undergoing partial nephrectomy for treatment of renal cell carcinoma. In addition, 14 kidneys with renal tumors were scanned immediately after radical nephrectomy and the specimens were subjected to simulated partial nephrectomy. Transverse and longitudinal real-time sonographic images were obtained with a 5 MHz. sector scanner or a 7.5 MHz. convex array transducer. With ultrasonography to define tumor extent and location, negative surgical margins were obtained in all 6 individuals undergoing partial nephrectomy. A negative surgical margin was obtained in 13 of the 14 radical nephrectomy specimens subjected to simulated partial nephrectomy. A small satellite lesion was not identified and not resected in 1 of the radical nephrectomy specimens. We found that intraoperative renal ultrasonography helps to identify the location and extent of deep intraparenchymal lesions. It also provides a guide for a more accurate nephrotomy, which facilitates the attainment of negative resection margins during partial nephrectomy. PMID- 1942266 TI - The incidence of multicentricity in renal cell carcinoma. AB - We established the frequency of cancer multicentricity in kidneys removed for renal cell carcinoma by examining 100 intact, formalin preserved kidneys with a diameter of less than 80 mm. (1987 to 1989). The mean diameter of the predominant tumors was 51 mm. (range 15 to 80 mm). After the capsules were removed the kidneys were serially sectioned at 3 mm. intervals, and cortical and intraparenchymal nodules were removed for histological examination. A total of 3 kidneys had multiple tumors found previously on routine pathological examination. In addition, we discovered another 11 nodules in 10 other kidneys. Four nodules had histological features consistent with carcinoma. The size of the nodules ranged from 2 to 5 mm. The rest of the nodules consisted of 3 adenomas, 1 adrenal rest, 1 oncocytoma coexisting with an adenoma and 1 carcinoma permeating through the lymphatic vessels. The mean size of the predominant tumors in the kidneys bearing multiple nodules was 49 mm. Therefore, we observed a 13% incidence of small renal nodules and a 7% multicentricity of renal cell carcinoma in kidneys from patients who underwent nephrectomy. PMID- 1942267 TI - What are the benefits of extended dissection of the regional renal lymph nodes in the therapy of renal cell carcinoma. AB - In a prospective study of 511 patients we compared the data of 320 who underwent systematically extended dissection of the regional lymph nodes with data of 191 who underwent only facultative dissection of the lymph nodes, which means that no lymph nodes had been removed or only a few were taken for staging purposes. Only patients without distant metastases and who were less than 72 years old were included. All patients were treated with a transabdominal approach. The incidence of positive nodes in the patients with systematically extended lymphadenectomy was 17.5% and for patients with facultative lymphadenectomy it was 10%. Survival rates of patients with facultative lymphadenectomy were 58% after 5 years and 40.9% after 10 years, compared to 66% and 56.1%, respectively, for patients with systematically extended lymphadenectomy (p less than 0.01). Patients with stage pT1-2 (Robson stage I) and pT3aN0M0 (Robson stage II) tumor obviously had the highest benefits with extended lymphadenectomy. Operative mortality was less than 1% after systematically extended lymphadenectomy and 3.8% after facultative lymphadenectomy. We conclude from our data that the systematic and extended lymphadenectomy improves the prognosis of patients with renal cell carcinoma without any additional operative risks. PMID- 1942268 TI - Spontaneous bladder rupture following augmentation enterocystoplasty. AB - Spontaneous bladder rupture following enterocystoplasty has been reported recently. The etiology remains unclear but appears to be multifactorial. The common factors among the reported patients are a high outlet resistance with total urinary continence and the presence of an augmented, dysfunctional native bladder. This combination may result in the development of high intravesical pressures or increased wall tension through several mechanisms, including over filling and active contraction in the bowel or detrusor. The presence of an abnormal detrusor may cause the wall tension to be unevenly distributed toward the bowel segment. Diagnosis requires a high degree of suspicion and prompt laparotomy with closure of the defect. Prevention depends on maintaining low bladder volumes and, thus, pressures. PMID- 1942270 TI - Bladder cancer in spinal cord injury patients. AB - A total of 8 cases of bladder cancer in spinal cord injury men (4 quadriplegics and 4 paraplegics) was seen at 3 medical centers since 1985. All 8 men had a hyperreflexic bladder and 3 of them had associated detrusor-sphincter dyssynergia. Upper tract changes were noted in 4 patients: 2 with distal ureterectasis and 2 with mild hydronephrosis. Only 1 of these men did not have historical films with which to compare results. Histology was transitional cell carcinoma in 6 men and squamous cell carcinoma in 2. Four patients presented with muscle invasion and 1 presented with diffuse carcinoma in situ involving the penile urethra. Three patients presented with superficial transitional cell carcinoma and 2 of them had progression to muscle invasion within 6 and 11 months. All but 2 of the patients with invasive disease underwent a radical operation and urinary diversion. Although followup is short (range 6 to 17 months), 5 patients are well with no evidence of disease and of the 3 who died 2 had no evidence of disease. We found a lower incidence of bladder cancer and a decreased percentage of squamous cell carcinoma than in previous reports, which may reflect an improvement in the lower tract management of these patients. Survival with appropriate bladder cancer treatment appears to correlate well with that of the ambulatory population. PMID- 1942269 TI - Clinical and immunological response to nifedipine for the treatment of interstitial cystitis. AB - Nifedipine is a calcium channel antagonist known to inhibit smooth muscle contraction and cell-mediated immunity. The clinical and local immune response to nifedipine was investigated in an open trial with 10 female interstitial cystitis patients, whose disease was diagnosed according to the consensus criteria developed in 1987 at a National Institutes of Health workshop. To evaluate the symptoms and clinical response of the patients objectively we scored the symptoms of frequency, urgency, nocturia, dysuria and suprapubic pain on a scale of 0 to 2. Nifedipine was administered as a single daily dose determined by a dose titration test. Urinary interleukin-2 inhibitor activity, a marker of cell mediated inflammation, was measured using a murine interleukin-2 dependent cell line. Before nifedipine therapy the symptom scores (total of the 5 symptoms) ranged between 5 and 9, and after 2 months they ranged between 0 and 6. Of the 9 patients followed for at least 4 months only 1 failed to have a significant clinical improvement, 5 showed at least a 50% decrease in symptom scores and 3 were asymptomatic. Drug side effects were minimal. Urinary interleukin-2 inhibitor activity before nifedipine therapy confirmed the presence of cell mediated inflammation. After 4 months of therapy interleukin-2 inhibitor activity was normal in 7 of 9 patients regardless of the severity of symptoms, which indicated that nifedipine exerted an immunosuppressive effect. Although our data suggest that nifedipine is an efficacious, well tolerated, convenient oral medication for the treatment of interstitial cystitis, the true value of nifedipine for patients with this disease must be determined by a prospective, randomized trial of nifedipine versus placebo. PMID- 1942271 TI - Tumors of the upper urinary tract: 10 years of experience. AB - We reviewed 108 patients with upper urinary tract tumors who underwent surgical treatment during a 10-year period (87 men and 21 women with a mean age of 63.5 years). Of the tumors 97% were unilateral and only 3 patients had bilateral tumors. Two-thirds of the patients had a single tumor focus and a third had 2 or more tumor foci. Additionally, there were 31 patients (28.7%) with previous and/or simultaneous bladder tumors. Nephroureterectomy was performed in 92 cases, nephrectomy in 6 and a conservative operation in 13. In 65 cases lymphadenectomy was added. The survival rates at 5 and 10 years were 67 and 65%, respectively. Of the patients 90% with cancer-related deaths had high grade tumors. Of the 15 patients with positive lymph nodes 87% died of metastasis compared to 8% of the 50 patients with negative lymph nodes. Nine patients (8.7%) had relapse in the upper urinary tract, 6 (5.8%) in the ipsilateral ureter and 3 (2.9%) in the contralateral ureter. Of these 3 patients 2 had recurrent multifocal bladder tumors. For patients who present with an upper urinary tract tumor the risk of a bladder cancer was approximately 9% and that of a contralateral urothelial tumor was 1%. PMID- 1942272 TI - Tumor enzymes and prognosis in transitional cell carcinoma of the bladder: prediction of risk of progression in patients with superficial disease. AB - The activities of 6 enzymes of carbohydrate metabolism were estimated in superficial transitional cell carcinomas from 103 patients undergoing transurethral resection of the bladder for the first time. The patients were followed by quarterly endoscopic examinations for a maximum of 81 months (median 33 months). During followup 24 patients had progressive disease. The activities of phosphofructokinase and phosphohexose isomerase were significantly lower in tumors from patients whose disease had superficially invaded the lamina propria (stage pT1) than in others in whom it was confined to the bladder mucosa (stage pTa). Similarly the activities of the 2 enzymes were significantly higher in well differentiated (grade 1) than in moderately well differentiated (grade 2) carcinomas. Univariate analyses using the log rank test showed that neither pathological stage nor malignancy grade of the carcinoma was a significant factor in predicting the risk of progression. Of the 6 enzymes, below median activities of phosphofructokinase, lactate dehydrogenase and phosphohexose isomerase were associated with a significantly increased risk of progression in these patients. Multivariate analyses using Cox's proportional hazards model showed that the activity of lactic dehydrogenase in superficial transitional cell carcinoma is an independent prognostic factor in predicting the risk of progression. It is postulated that the measurements of the activities of the 3 enzymes in tumors from patients with superficial transitional cell carcinoma might help to select individual patients with a high risk of progression for adjuvant intravesical treatments. PMID- 1942273 TI - Effect of patient positioning on urethral mobility: implications for radical pelvic surgery. AB - Patient positioning is of critical importance in the successful performance of several radical pelvic operations. Adequate exposure of the prostatic apex is vital in ligating the dorsal vein complex and performing vesicourethral anastomosis. To test the effect of different patient positions on urethral mobility, we conducted a prospective controlled study measuring the relative cephalad displacement of the prostatic apex in 3 positions, that is the supine, frog-leg and dorsal lithotomy positions. A combination of radiographic and cystoscopic techniques was used to mark the position of the prostatic apex. Each patient served as his own control. Of the 24 patients studied for a variety of urological complaints 19 (79%) had an increased cephalad displacement of the prostatic apex while in the frog-leg position compared with the dorsal lithotomy position. The mean gain was 0.5 cm. (p greater than 0.5). A total of 16 patients showed improvement while in the frog-leg position over the supine position with a mean advantage of 0.39 cm. (p greater than 0.05). Patient age, pelvic depth, pelvic circumference and prostatic urethral length had no predictive value in selecting an optimal position. PMID- 1942274 TI - Prevalence, incidence and correlates of urinary incontinence in healthy, middle aged women. AB - The prevalence, incidence and correlates of urinary incontinence were studied in a community-based sample of 541 healthy, middle-aged women 42 to 50 years old. Participants were evaluated on 2 occasions approximately 3 years apart. Of the participants 58% reported urine loss at some time and 30.7% reported incontinence on a regular basis at least once per month. During 3 years the cumulative incidence of regular incontinence in previously continent women was 8.0%. Among those with regular incontinence 64.9% said the volume of loss was 1 or 2 drops, while 35.1% reported that they needed to change their garments. Only 25.5% of the patients had sought treatment. Continence status was significantly related to body mass index and race but not to patient age, parity, caffeine or alcohol intake, smoking, physical activity, prior gynecological surgery or several psychological variables. The results indicate that urinary incontinence is common among middle-aged women. That few seek treatment suggests a need for more information about women's attitudes toward incontinence and more attention to this problem by health care providers. PMID- 1942275 TI - Venous leaks: anatomical and physiological observations. AB - A total of 50 patients with impotence underwent cavernosometry and cavernosography with intracavernous injection of vasoactive drugs. Several hemodynamic parameters were analyzed, including the pressure response curve after injection of vasoactive drugs and infusion of saline, the volume required to achieve erection, venous outflow resistance, erection maintenance infusion rate, rate of pressure decrease after discontinuation of infusion and post-infusion steady state pressure. On the basis of cavernosometric findings, venous leakage was ruled out in 4 patients. In the remaining 46 patients leak sites visualized during cavernosography included superficial dorsal vein in 1 (2.2%), deep dorsal vein in all 46 (100%), cavernous veins in 32 (69.6%), glans in 19 (41.3%) and corpus spongiosum in 14 (30.4%). Aberrant veins were documented in 7 patients (15.2%) communicating with the saphenous vein in 4 (8.9%), scrotal veins in 2 (4.4%) and femoral veins in 1 (2.2%). Eight patients (17.4%) had leakage through the deep dorsal vein as the only venous site, 17 (36.9%) had leakage through 2 venous sites, 14 (30.4%) had leakage through 3 venous sites and 7 (15.2%) had leakage through 4 venous sites. Correlations among hemodynamic and radiographic observations allowed the identification of 4 different types of cavernosometric findings. While type I represented normal penile vascular findings, types III and IV represented venous leakage. Type II could represent no leak, a mild leak or an undetected arterial problem. Accuracy of interpretation of a study may be improved by taking more than 1 parameter into consideration, including erection maintenance infusion rate, intracavernous pressure decrease within the first 5 seconds after discontinuation of infusion and the final steady state intracavernous pressure. The majority of patients have more than 1 leak site (82.6%). The most commonly combined sites of leakage are the deep dorsal and cavernous veins. PMID- 1942276 TI - Comparison of the diagnostic value of pump and gravity cavernosometry in the evaluation of the cavernous veno-occlusive mechanism. AB - We performed cavernosometry in 96 patients with erectile dysfunction. Two different techniques were compared: pump cavernosometry using a roller pump as the inflow source and gravity cavernosometry using an infusion set as the inflow source. We conclude that the diagnostic value of both techniques is comparable. In pump cavernosometry maintenance flow is the most accurate parameter of veno occlusive function. Gravity cavernosometry has the advantages of simplicity, cost effectiveness and a lower complication rate. Incomplete cavernous smooth muscle relaxation appeared to be limiting the diagnostic value of both techniques. PMID- 1942277 TI - Interpretation and quantification of penile blood flow studies using duplex ultrasonography. AB - Duplex ultrasound scanning of the penis combined with intracorporeal pharmacological stimulation of an erection provides an accurate, relatively noninvasive functional assessment of cavernous artery blood flow. Various criteria described for normal have been based on either blood flow velocity alone or the combination of blood flow velocity and arterial dilatation of each cavernous artery. Unfortunately, less than 20% of impotent men have classical arterial anatomy and the aforementioned normal criteria do not take into account the various possible anatomical and acquired anomalies that can exist. In addition, the multiplicity of parameters used to describe normal are cumbersome to use for patient comparison and statistical analysis. In this study, 4 indexes were developed to express the results of a duplex ultrasound penile blood flow study and they were tested in an impotent population comprised of 75 men with arterial disease and 33 men with impotence due to neurogenic or psychogenic causes. A significant difference was observed between these 2 groups using all 4 indexes (p less than 0.001). However, the penile blood flow index, which incorporated velocity and dilatation, performed best as determined by sensitivity, specificity and receiver operating characteristics. Based on the results of this study, the penile blood flow index, which represents the summation of the percentage of dilatation and peak blood flow velocity of each cavernous artery, provides an accurate reflection of total penile blood flow as measured by duplex ultrasound. PMID- 1942278 TI - The penile plication procedure: an alternative method for straightening penile deviation. AB - The number of reported cases of congenital and acquired penile deviation is evidently increasing. We describe our experience with the penile plication procedure, which we used to treat 40 patients with penile deviation. Postoperatively, all patients regained the ability for sexual intercourse, with potency remaining unimpaired. Of the patients 96% were completely satisfied with the result of the operation. Sustained complications have not been observed. To avoid major trauma the surgical intervention should not include removal of ellipsoids from the penile tunica albuginea as proposed by Nesbit. Since the penile plication method produces equally good results in terms of performance and appearance, this therapy should be preferred. PMID- 1942279 TI - Squamous cell carcinoma of the penis: accuracy of tumor, nodes and metastasis classification system, and role of lymphangiography, computerized tomography scan and fine needle aspiration cytology. AB - Among 118 patients with squamous cell carcinoma of the penis treated at our cancer institute between 1956 and 1989, we analyzed the accuracy of classification, using the tumor, nodes and metastasis system. We analyzed the role of lymphography, computerized tomography and fine needle aspiration cytology as additional staging procedures. The primary tumor (T category) was classified incorrectly in 26% of the cases. Overstaging was noted in 10% of the cases because of unsuspected infiltration and overstaging was noted in 16%. Overstaging occurred because of edema and infection masking the actual size and giving a misconception of infiltration, and also because of primary presentation as large exophytic tumors with no or minimal histopathological infiltration. When the regional lymph nodes were categorized simply as positive or negative 80% of the tumors were classified correctly and 20% incorrectly (13% were false positive and 7% were false negative). Regional lymph node invasion that escaped clinical examination was not detected by any imaging examination or fine needle aspiration cytology study. Positive findings were found only in patients with clinically suspected nodes. The classification of regional nodes by clinical examination only is hardly improved by additional imaging studies. Clinical decisions with respect to the management of regional lymph nodes should not be based on negative findings of lymphangiography, computerized tomography or fine needle aspiration cytology. In patients with proved metastasis additional imaging may be of some help in the detection of pelvic node invasion and the determination of the extent of involvement. We recommend lymphangiography as the examination of choice. PMID- 1942280 TI - Color-coded duplex sonography for diagnosis of testicular torsion. AB - By color-coded duplex sonography moving structures are visualized as red or blue colors within a normal gray-scale B-mode ultrasound image. Thus, blood flow even within small vessels can be visualized clearly. Color-coded duplex sonographic examination was performed in 11 patients who presented with scrotal pain. This method proved to be reliable to differentiate between testicular torsion and testicular inflammation. By clearly demonstrating a lack of intratesticular blood flow in testicular torsion, while avoiding flow in scrotal skin vessels being misinterpreted as intratesticular blood flow, this method significantly decreases the number of patients in whom surgical evaluation is necessary to exclude testicular torsion. PMID- 1942281 TI - Squamous cell carcinoma of the scrotum: long-term followup of 14 patients. AB - Squamous cell carcinoma of the scrotum was diagnosed in 14 patients from 1945 to 1990. Patient age at diagnosis ranged from 40 to 73 years, with the mean age of 62 years. The most common presentation was a solitary skin lesion but inguinal adenopathy was noted in 5 patients (36%). The mean delay to diagnosis for all patients was 22 months, with a range of 2 months to 10 years. Predisposing factors included psoriasis treated with coal tar or arsenic, human papillomavirus infection and multiple cutaneous epitheliomas. The primary lesion was treated by local or wide local excision in all 14 patients. In addition, 4 patients underwent inguinal lymphadenectomy and 3 underwent radiotherapy to the pelvic and inguinal lymph nodes. Mean followup for all patients was 6 years. However, 11 patients were disease-free with a mean followup of 7 years. Improved prognosis was noted in patients with locally confined disease or carcinoma in situ only. There was no correlation between grade of tumor and survival. All patients with stages A1 and B disease treated with wide local excision and/or inguinal lymphadenectomy have done well on followup. Radiotherapy does not appear to impact on survival for patients with high stage disease. PMID- 1942282 TI - Familial patterns of prostate cancer: a case-control analysis. AB - Epidemiological data have not yet enabled physicians to look beyond age and race to identify men at increased risk for prostate cancer. We conducted a hospital based case-control study of familial patterns of prostate cancer with self reported data from a risk-factor questionnaire. There were 385 patients with histologically confirmed prostate cancer, and 385 race and age-matched (+/- 5 years) controls with other cancers. Family history, available for 378 patients and 383 controls, was positive for prostate cancer in 13.0% versus 5.7%, respectively. The difference was significant at p = 0.01. The over-all age adjusted risk estimate for men with a first-degree relative with prostate cancer was significantly elevated (odds ratio of 2.41), as were the individual risk estimates for having a father or brother with prostate cancer (odds ratio of 2.24 and 2.66). Having a second-degree relative (grandfather or uncle) with prostate cancer also conferred elevated but not statistically significant risk. These data accord well with the few previously published case-control studies of familiarity of prostate cancer. On the basis of these findings, one should consider recommending participation in early detection programs for prostate cancer in a man whose father or brother has had the disease. PMID- 1942283 TI - Failure of open radioactive 125iodine implantation to control localized prostate cancer: a study of 41 patients. AB - We studied 41 patients with localized prostate cancer who underwent bilateral pelvic lymphadenectomy with open insertion of radioactive 125iodine. Followup was a minimum of 5 years. Of the patients 13 died: 10 of recurrent prostatic adenocarcinoma (including 4 of 5 with pathological stage D1 cancer) and 3 of unrelated causes within 2 years of implantation without clinical evidence of prostate cancer. Of the 28 remaining patients 16 have known recurrence of cancer (positive bone scan and increasing prostate specific antigen (PSA) level or positive tissue biopsy]. Six patients have strong suspicion of local recurrence with elevated PSA levels (greater than 4.0 in 5) and increasing induration on digital rectal examination. Only 6 of the 41 patients (14.6%) are without evidence of disease. Openly implanted radioactive 125iodine does not appear to control effectively adenocarcinoma of the prostate. PMID- 1942284 TI - Prognostic factors in progression-free survival and corrected survival in patients with advanced prostatic cancer: results from a randomized study comprising 150 patients treated with orchiectomy or estrogens. AB - In a population-based randomized study comparing 150 patients with advanced prostatic cancer treated with orchiectomy or estrogen, some possible prognostic factors were analyzed. The observation period was 78 to 114 months. M category, T category, tumor grade, performance status, pain, prostatic acid phosphatase, sedimentation rate, hemoglobin and serum creatinine level were all statistically significantly related to the interval to progression and to disease-specific death on univariate analyses. Variables that were statistically significant on multivariate analyses were M category, T category, sedimentation rate and patient age. The sedimentation rate predicted the intervals to progression and to disease specific death, with the relative hazard and 95% confidence interval for the latter end point being 1.018 (range 1.010 to 1.027) for each millimeter increase in sedimentation rate per hour. An analysis that was stratified according to the extent of the disease as measured on a bone scan showed that the sedimentation rate was the only prognostic factor of statistical significance with an estimate of relative hazard of 1.52 if the sedimentation rate was elevated 20 mm. per hour. Progression-free survival but not disease-specific survival was statistically significantly better in the estrogen group (relative hazard 0.47), as assessed by multivariate analysis in which all variables were taken into account. PMID- 1942285 TI - Vertebral mineral content in diet-dependent and diet-independent hypercalciuria. AB - The vertebral mineral content was measured using dual photon absorptiometry in 41 calcium stone patients with idiopathic hypercalciuria. These patients had been previously divided into 2 groups (diet-dependent and diet-independent hypercalciuria) during a low sodium and low calcium diet. In some of the patients (11 with diet-dependent and 11 with diet-independent hypercalciuria) the vertebral mineral content was evaluated in relation to serum ionized calcium, intact parathyroid hormone, alkaline phosphatase and osteocalcin determined after a low sodium and low calcium diet. The vertebral mineral content, expressed as Z VMD, was normal in diet-dependent and lower in diet-independent hypercalciuric stone patients (-0.30 +/- 1.19 versus -0.26 +/- 1.18, p less than 0.02). In 7 of 21 patients (33.3%) the vertebral mineral content was less than 2 standard deviations of the normal value, indicating a true involvement in bone metabolism. Serum intact parathyroid hormone and osteocalcin levels were not different from the controls in both groups, while alkaline phosphatase activity and ionized calcium were higher in diet-independent hypercalciuric patients. Serum ionized calcium was negatively correlated with bone vertebral density. The results suggest that an increased bone turnover may be a primary event in causing hypercalciuria in calcium stone patients unable to decrease urinary calcium to less than the calcium intake. PMID- 1942286 TI - Handling the "glidewire". PMID- 1942287 TI - Ileocecocystoplasty for the management of refractory neurogenic bladder: surgical technique and urodynamic findings. AB - A total of 21 incontinent adults with a neurogenic bladder who were refractory to conservative management underwent a modified technique of ileocecocystoplasty. Followup ranged from 1 to 6 years (mean 3.1 years). To ensure a wide anastomosis the augmentation was accomplished by suturing a detubularized ileocecal patch to a large posterior based bladder flap anchored to the psoas muscles. Postoperatively 20 of 21 patients were continent. The remaining woman was cured after surgical correction of sphincteric incontinence. Mean bladder capacity increased from 185 +/- 17 to 595 +/- 43 ml. (standard error). Mean maximum detrusor pressure decreased from 53 +/- 6.3 to 16 +/- 2.3 cm. water (p less than 0.0001). Followup revealed a persistently large capacity, low pressure reservoir in all patients. No patient required anticholinergic medication. None experienced acid-base imbalance, tumors in the augmented bladder or upper tract deterioration. We conclude that this technique of ileocecocystoplasty is suitable for the management of patients with a refractory neurogenic bladder. PMID- 1942288 TI - Effects of pinacidil on detrusor instability in men with bladder outlet obstruction. AB - In a double-blind, crossover study the effect of the potassium channel opener pinacidil (N''-cyano-N'4-pyridyl-N-1,2,2-trimethylpropylguanidine monohydrate) at 25 mg. per day was evaluated in 10 patients with detrusor instability and bladder outlet obstruction. Nine patients completed the study: in 7 pinacidil was without significant effect on urodynamic variables and in 2 detrusor instability was not found at the end of the pinacidil period. Maximum urinary flow, frequency and nocturia were unchanged during pinacidil treatment, compared to the initial test and the placebo period. There was a significant decrease in standing blood pressure but heart rate was stable throughout the study. No patient experienced distinct symptomatic improvement or side effects during pinacidil treatment. The results suggest that pinacidil at the dosage given is not effective for treatment of unstable detrusor contractions associated with bladder outflow obstruction. PMID- 1942289 TI - Ureteral reimplantation: a comparison of results with the cross-trigonal and Politano-Leadbetter techniques in 120 patients. AB - A review of 120 children who underwent ureteral reimplantation by the cross trigonal or Politano-Leadbetter technique is presented. Over-all success rates (no postoperative reflux or ureteral obstruction) were 96.7% for the Politano Leadbetter method and 97.8% for the cross-trigonal technique. There were no failures using either method in patients operated upon for primary vesicoureteral reflux. PMID- 1942290 TI - Leukemic relapse presenting with ureteral obstruction caused by granulocytic sarcoma. PMID- 1942291 TI - Deoxyribonucleic acid and cytological detection of Y-containing cells in an XX hypospadiac boy with polyorchidism. AB - A hypospadiac boy with a hypoplastic penis and an apparent 46,XX karyotype in blood and testis cultures is described. Exploratory laparotomy and bilateral gonadal biopsy revealed the presence of 2 testes in the right and 1 in the left hemiscrotum, each of which only showed hypoplastic testicular tissues histologically. Uncultured testis smears showed Y chromatin in approximately 20% of the cells. Also, the Southern blot and polymerase chain reaction analyses detected a weak but distinct signal of Y chromosome-derived deoxyribonucleic acid sequences in the perineal skin but not in the blood lymphocytes. The results indicated that the boy had a small proportion of Y chromosome-containing cells in the form of mosaicism in limited tissues, such as the testes and perineal skin. This finding may have implications in the genesis of testes in some cases of XX patients, and true hermaphrodites or male pseudohermaphrodites with an apparent 46,XX karyotype. To our knowledge, this appears to be the first case of polyorchidism with an identified chromosome abnormality. PMID- 1942292 TI - Unusual echinococcal cyst. AB - We report a case of a single echinococcal cyst that originated from the liver, and occupied the upper right retroperitoneal space and kidney. The diagnostic problems and the surgical procedure are discussed. PMID- 1942293 TI - Use of methylene blue and selective embolization of the pudendal artery for high flow priapism refractory to medical and surgical treatments. AB - High flow priapism is often treated effectively with intracavernous vasoconstrictive agents or surgical shunting. If these maneuvers fail treatment is unclear. A 21-year-old black man, who had failed previous pharmacological and surgical therapies, temporarily (8 hours) responded to intracavernous methylene blue, which is known to antagonize endothelial derived relaxation factor. Recurrent priapism was managed successfully by embolization of the left internal pudendal artery with absorbable gelatin sponge. Review of the literature reveals that only 7 patients have been managed with arterial embolization and our case represents the first in which intracavernous methylene blue produced detumescence. PMID- 1942295 TI - Syndrome of inappropriate antidiuretic hormone following tuberculous epididymo orchitis in renal transplant recipient: case report. AB - A rare case of the inappropriate antidiuretic hormone syndrome after tuberculous epididymoorchitis in a renal transplant recipient is described. Orchiectomy was performed because of a cold abscess, following which clinical improvement was noted. PMID- 1942294 TI - Penile malignant melanoma in association with squamous cell carcinoma of the penis. AB - We report a case of malignant melanoma of the penis in association with penile squamous cell cancer. Previous regional lymphadenectomy did not prevent subsequent development of regional recurrence. This clinical presentation and the literature are discussed. PMID- 1942296 TI - Prostatic carcinosarcoma: case report and review of literature. AB - True carcinosarcoma of the prostate is a rare neoplasm, with only 9 cases well documented by immunocytochemistry and ultrastructural examination. We report a case of an unresectable pelvic tumor studied at autopsy. The primary prostatic neoplasm and pulmonary metastases were composed of well differentiated adenocarcinoma admixed with foci of leiomyosarcoma and osteosarcoma. The sarcomatous components showed reactivity with vimentin and desmin, did not express prostatic acid phosphatase (PAP) and prostate specific antigen (PSA), and contained myofilaments on electron microscopic examination. Positive staining of the carcinomatous component for PAP and PSA was noted. These findings confirm the mixed epithelial and mesenchymal components in primary and metastatic sites, and support the diagnosis of true prostatic carcinosarcoma. PMID- 1942297 TI - Bilateral excision of perinephric fat and fascia (Gerota's fasciectomy) in the treatment of intractable chyluria. AB - A case is described of a 59-year-old black man with massive chyluria, probably due to previous infection with Wuchereria bancrofti. Notably, no edema was present despite a urinary protein loss of 40 gm. per day resulting in a serum albumin level of 13 gm./l. Conservative treatment after lymphography, including prolonged bedrest and a medium chain triglyceride diet, was unsuccessful. Bilateral excision of the perinephric fascia and fat (Gerota's fasciectomy) in 2 separate operative sessions finally resulted in complete resolution of the chyluria. PMID- 1942298 TI - Re: A further study of oxalate bioavailability in foods. PMID- 1942299 TI - Re: The loop-loosening procedure for urination difficulties after Stamey suspension of the vesical neck. PMID- 1942300 TI - Re: The role of radical cystectomy in the management of high grade superficial bladder cancer (Pa, P1, PIS and P2) PMID- 1942301 TI - Re: Classification of sexual dysfunction for management of intracavernous medication-induced erections. PMID- 1942302 TI - Re: Clinical significance of ultrastructural findings in the corpora cavernosa of normal and impotent men. PMID- 1942303 TI - Re: Hyperprolactinemia and impotence: why, when and how to investigate. PMID- 1942304 TI - Re: Sudden death due to disease flare with luteinizing hormone-releasing hormone agonist therapy for carcinoma of the prostate. PMID- 1942305 TI - Re: Suprapubic approach for bilateral orchiectomy and placement of testicular prostheses and re: Subepididymal orchiectomy: the acceptable alternative. PMID- 1942306 TI - Urinary tract infections: need for pure culture technology in clinical laboratory diagnosis. PMID- 1942307 TI - A new model of nephrolithiasis involving tubular dysfunction/injury. AB - To better understand the pathogenesis of nephrolithiasis, we developed a new animal model that closely mimics human calcium oxalate stone disease. Rats were treated with a regimen that combines moderate hyperoxaluria (produced by 10 days of feeding with 3% ammonium oxalate) with mild proximal tubular injury/dysfunction (produced by 8 daily injections of gentamicin sulfate -40 mg./kg.). This combined treatment caused a marked increase in the incidence of calcium oxalate crystals and stones over that seen in animals treated with oxalate or gentamicin alone. Using a semiquantitative scoring system for estimating the abundance of crystals in coronal sections of kidneys, we found that 63% of animals receiving gentamicin plus oxalate showed "moderate" numbers of crystal, as compared to 8% of animals receiving oxalate alone; and the majority of the crystals occurred in the papilla, a pattern similar to that seen in human stone disease. Untreated rats and rats treated with gentamicin alone did not exhibit calcium oxalate crystals or stones. Despite the abundance of crystals and stones, animals receiving gentamicin plus oxalate retained relatively normal renal function as judged by creatinine clearance. Thus, the model has several advantages over preexisting models of nephrolithiasis. Crystal and stone deposition develop rapidly (within 14 days). The pattern of deposition resembles that seen in human stone disease and renal function remains relatively normal. These findings indicate that this model of nephrolithiasis may prove useful for studies of the pathogenesis of stone disease. Moreover, they suggest that renal tubular injury and/or dysfunction may produce conditions conducive to the formation and growth of calcium oxalate stones. PMID- 1942308 TI - Mechanisms of solute transport following urinary diversion through intestinal segments: an experimental study with rats. AB - This investigation employs an in vivo intestinal perfusion model in rats in order to study the mechanisms of intestinal electrolyte transport as it relates to the acidosis associated with urinary diversion. This investigation demonstrates that urinary ammonium is directly related to net sodium secretion and that chloride absorption is directly related to net bicarbonate secretion. The general mechanisms described are consistent with previously described mechanisms of intestinal electrolyte transport but demonstrate substantial differences in net directional movements compared to normal intestinal transport. This study provides a working model for further investigation and solutions to the management of the acidosis associated with urinary diversion. PMID- 1942309 TI - Toxicity to the urothelium of calcium chelating agents for chemolysis. AB - Solutions, based on calcium chelating agents, with excellent prospects as litholytic agents in vitro were tested on toxicity to the mucosa of the bladder of the rat. The following compounds were tested at a concentration of 12.5 mM., buffered with triethanolamine 0.2 M at pH 8 and 8.5: ethylenediaminetetra acetic acid with as cation H2+, Li+, Na+, K+, and Cs+, trans-cyclohexane-1.2 diaminetetra acetic acid (cations H+, Na+, K+), diethylenetriamine penta acetate (cations H+, Na+, K+), disodiumethyleneglycol-bis (2 aminoethyl) tetra acetic acid and disodium hydroxyethylethylenediamine tetra acetate. All agents were found to be very noxious to the bladder mucosa of the rat and are unlikely to be safe for clinical use. PMID- 1942310 TI - DNA, RNA and immunohistochemical characterization of the HER-2/neu oncogene in transitional cell carcinoma of the bladder. AB - HER-2/neu overexpression appears to play a role in determining the malignant potential of some human cancers. To date, no urothelial malignancies appear to have been evaluated for HER-2/neu DNA amplification, mRNA expression and protein overproduction. By Southern hybridization we detected DNA amplification and a possible structural rearrangement of the HER-2/neu oncogene in one of 12 bladder tumors. A 14 kb DNA fragment in addition to the expected 12.5 Kb fragment was found. Additionally, the HER-2/neu oncogene was amplified sixfold in the tumor compared to placental DNA. Five of 14 (36%) bladder tumors overexpressed HER 2/neu mRNA three to 38-fold compared to normal urothelium. HER-2/neu overexpression occurred in superficial and invasive tumors. Immunohistochemical analysis was performed on the one tumor with DNA amplification and the 14 tumors evaluated for mRNA expression. The tumor with DNA amplification and three of the five tumors with HER-2/neu mRNA overexpression stained positively for the p185HER 2/neu protein. These findings suggest that DNA amplification occurs infrequently in bladder cancer. Thirty-six percent of bladder cancers overexpress HER-2/neu mRNA. Immunohistochemical analysis with a p185HER-2/neu polyclonal antibody, on formalin fixed, paraffin embedded tissue, was specific for HER-2/neu overexpression but not as sensitive as Northern analysis. PMID- 1942311 TI - The growth of MAT-LyLu rat prostatic adenocarcinoma can be prevented in vivo by polyamine deprivation. AB - The combination of inhibitors of ornithine decarboxylase and polyamine oxidase, and of antibiotics suitable for the (partial) decontamination of the gastrointestinal tract, with a polyamine deficient diet, is responsible for the almost complete inhibition of the growth of MAT-LyLu prostatic adenocarcinoma. In the tumor-bearing animals, erythrocyte spermidine levels were reduced, but spermine concentrations were increased. As has been previously observed, the increase in erythrocyte spermine level was associated with an enhancement of malignant cell death. Adriamycin administration did neither diminish tumor growth, nor potentiate the antitumor effect of polyamine deprivation treatment. Interruption of the polyamine deprivation treatment was accompanied by a significant enhancement of tumor growth. Since polyamine deprivation causes only reversible growth inhibition, it seems not appropriate as a monotherapy. PMID- 1942312 TI - Antimicrobial tissue penetration in a rat model of E. coli epididymitis. AB - Following induction of unilateral epididymitis by intratesticular injection of E. coli, a single intraperitoneal dose of amdinocillin, ampicillin, doxycycline, tobramycin, or trimethoprim/sulfamethoxazole was administered to five groups of rats. The animal was sacrificed serially and concentrations of antibiotic in serum, infected epididymides, and non-infected epididymides were determined by high performance liquid chromatography. The ratio of infected to non-infected tissue area under the curve values was 1.05 for trimethoprim, 1.58 for sulfamethoxazole, 1.67 for amdinocillin, 2.01 for tobramycin, 2.25 for doxycycline, and 2.58 for ampicillin. Except for trimethoprim, infected tissue concentrations were significantly greater than compared to uninfected epididymal levels (p less than 0.05). Antibiotic concentrations in infected epididymides compared to serum revealed overall penetration of 34% for amdinocillin, 66% for sulfamethoxazole, 70% for ampicillin, 76% for tobramycin, 256% for trimethoprim, and 257% for doxycycline. In a rat model of epididymitis, trimethoprim and doxycycline demonstrated the greatest degree of epididymal penetration compared to serum. All antibiotics except trimethoprim had significantly greater penetration into infected tissue when compared to non-infected epididymal tissue. PMID- 1942313 TI - The therapeutic impact of dipyridamole: chemopotentiation of the cytotoxic combination 5-fluorouracil/cisplatin in an animal model of human bladder cancer. AB - Using an in vivo assay of tumor cytotoxicity (the subrenal capsule assay in nude mice), two therapeutic strategies for the treatment of advanced human transitional cell carcinoma have been evaluated: 1) the use of 5-fluorouracil in combination with cisplatin and 2) the ability of the chemosensitizer dipyridamole to augment the cytotoxicity of CDDP and 5FU. A moderate cytotoxic response of human TCC line DU-4284 to single agent CDDP was seen; it was dose dependent at minimally toxic doses [maximal cytotoxicity--27% tumor survival (%TS) relative to control]. Efficacy was further significantly enhanced by the addition of DP [11%TS (p = .008)]. 5FU at minimally toxic doses (100 and 150 mg./kg.) also demonstrated moderate dose-dependent cytotoxic activity (35 and 31%TS, respectively) which was further enhanced by DP [21%TS (p = .03) and 18%TS (p = .05)]. A constant dose ratio of CDDP/5FU when diluted showed dose-dependent cytotoxicity; at the highest dose dilution studied, substantial cytotoxic efficacy (17%TS) was attained. The cytotoxicity of 5FU/CDDP was order independent (p = .95). The addition of DP to this combination (5FU/CDDP) further enhanced efficacy; host toxicity was not substantially enhanced. A multiple regression analysis confirmed a statistically significant effect of DP with both CDDP and 5FU (p = .001 and 0.0001, respectively); tests for trend showed no significant interaction (p = 0.33 for all models). It is concluded that, in this preclinical in vivo model of human bladder cancer, 1) CDDP and 5FU show substantial enhanced efficacy when combined, and 2) DP serves as an in vivo chemosensitizer of both CDDP and 5FU; DP further augments the efficacy of this binary combination. These data would indicate the potential of this ternary (5FU/CDDP/DP) drug therapeutic regimen for clinical trial to treat advanced bladder cancer. PMID- 1942314 TI - Proliferative glomerulopathy following extracorporeal shock wave lithotripsy in the pig. AB - Histopathologic changes after extracorporeal shock wave lithotripsy (ESWL) were studied in kidneys from four groups of nine pigs treated with an EDAP LT-01 (five pigs/group) or Dornier HM3 (four pigs/group) lithotripter, and sacrificed at time zero, 48 hours, one week and one month. Treatment dosages increased consistently within each group. Samples from primary treatment area and opposite control kidney were processed routinely for light, immunofluorescence, and electron microscopy. Tubulointerstitial changes included hemorrhages at zero and 48 hours and scars at one week and one month with both lithotripters. Glomerular mesangial cell proliferation started by 48 hours and increased over one month in treated and control samples. Electron microscopy showed mesangial deposits and phagolysosomes. Immunofluorescence showed trace IgG, zero IgM, and 1-2+ C3. The conclusions were: 1) Mesangial cell proliferation associated with deposits of C3 and phagocytosis of cellular debris starts by 48 hours post ESWL and increases thereafter, with both Dornier and EDAP lithotripters. 2) The pathogenesis appears to involve phagocytosis of circulating cellular debris and red blood cell fragments presumed to derive from breakdown of the hematoma caused by the lithotripsy. PMID- 1942315 TI - Basal and acetylcholine-stimulated nitric oxide formation mediates relaxation of rabbit cavernous smooth muscle. AB - Externally applied acetylcholine (ACh) in human corpus cavernosum has been shown to cause endothelium-dependent smooth muscle relaxation. Changes in isometric tension in rabbit cavernous smooth muscle strips mounted in organ bath chambers were monitored in the presence of blocking agents. Nitric oxide (NO) is known as an endothelium-derived relaxation factor (EDRF). Addition of specific inhibitors of nitric oxide synthesis, such as L-n-monomethyl arginine (L-NMMA) at 5 x 10(-4) mol/l.. or L-n-nitro arginine (L-NOARG) at 2 x 10(-4) mol/l. to strips precontracted with phenylephrine (PE) at 3.16 x 10(-6) mol/l. led to significant increases in tension. In the presence of L-NMMA or L-NOARG, relaxing effects of ACh at 10(-8)-3.16 x 10(-5) mol/l. mediated by muscarinic receptors were almost completely abolished. These data indicate that rabbit cavernous smooth muscle is under the control of basal NO release. They constitute strong evidence that cholinergically induced endothelial formation of NO plays a crucial role in relaxing cavernous smooth muscle. PMID- 1942316 TI - Urethral pressure and pressure variations in healthy fertile and postmenopausal women with reference to the female sex hormones. AB - The impact of female sex hormones on the rhythmic urethral pressure variations (UPV) was analysed based on data from one hour urethral pressure recordings from 10 healthy fertile female volunteers measured three times during the menstrual cycle and from 12 healthy postmenopausal women measured twice within two months. The mean maximum urethral pressure (mMUP) and the mean maximum urethral closure pressure (mMUCP) had a median value of 66.5 (Interquartile 58.0-86.0) and 60.0 (49.0-80.0) cm.H2O respectively in the healthy fertile females. The postmenopausal women had a significantly lower mMUP and mMUCP of 55.5 (48.5-58.5) and 43.5 (35.5-47.0) cm.H2O) respectively. Rhythmic UPV was recorded inhealthy fertile and postmenopausal women. Frequency analysis of the UPV revealed a frequency spectrum from 0.0015 to 0.035 Hz on top of which were respiration fluctuations and vascular pulsations. The UPV amplitude was related to the mMUP and increased with increasing mMUP. The parameters analysed were stable during the menstrual cycle and during menopause. Thus no difference in the UPV frequencies or amplitudes was observed between the healthy fertile and the postmenopausal women. The investigation shows that the pressure variation in urethra apparently is not modulated by female sex hormones. PMID- 1942317 TI - A canine model of cyclosporine enhanced ischemic renal injury. AB - Clinical reports of increased graft primary non function in patients receiving cyclosporine in whom the anastomosis time is prolonged (greater than 30 minutes) suggest a synergism between the nephrotoxic effects of cyclosporine and the ischaemia occurring during transplantation. Using unilaterally nephrectomised greyhound dogs, sixty minutes ischaemia and cyclosporine 10 mg./kg./day we have produced an animal model of cyclosporine enhanced ischaemia renal failure. Structural and functional data suggests the proximal tubule is the main site of injury. PMID- 1942318 TI - Prevention of cyclosporine enhanced ischaemic renal injury using induced hypothermia. AB - Cyclosporine is associated with an increased incidence of graft primary non function and poorer long term graft function in patients with prolonged ischaemia times. We evaluated the role of hypothermia in preventing this synergism between the nephrotoxic effects of cyclosporine and ischaemia in a canine model. Induced renal hypothermia prevented this synergism. PMID- 1942319 TI - Autonomic dysreflexia and its urological implications: a review. PMID- 1942320 TI - Imaging of renal cancer using positron emission tomography with 2-deoxy-2-(18F) fluoro-D-glucose: pilot animal and human studies. AB - The feasibility of imaging renal cancers with 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) and whole-body positron emission tomographic scanning was assessed in nude mice with human renal adenocarcinoma xenografts and then in 5 patients with primary renal cancer (4 adenocarcinomas and 1 transitional cell carcinoma). In nude mouse biodistribution studies tumor FDG uptake was maximal at 0.33 to 2 hours but tumor-to-blood ratios increased continuously to 7.8/l. by 4 hours after intravenous FDG injection. In all 5 patients primary and metastatic tumors were imaged within 1 hour by FDG positron emission tomography following intravenous injection of the FDG. By contrast, an hepatic hemangioma did not accumulate FDG. In summary, FDG metabolic and anatomical imaging of primary and metastatic renal cancer is feasible and in these pilot studies appears to be a promising imaging methodology that may be further enhanced by delayed imaging times. Additional study in a larger number of patients is essential to define better the accuracy and potential clinical use of this method. PMID- 1942321 TI - The urine specific gravity dipstick: a useful tool to increase fluid intake in stone forming patients. AB - High fluid intake is the only preventive dietary measure that can be recommended to all patients with stones. However, the efficacy of dietary advice given to patients is unknown. We compared the impact of dietary advice to increase hydration (group 1, 57 patients) and of no dietary advice (group 2, 83 patients) on 24-hour urine volume. No significant difference was noted between groups 1 (1,624 ml.) and 2 (1,732 ml.). We then determined if urine specific gravity dipsticks could help patients increase the 24-hour urine volume. A correlation between 24-hour urine volume and mean urine specific gravity was performed on 263 randomly chosen patients. There was an inverse relationship between urine specific gravity and 24-hour urine volume with a correlation coefficient of 0.522 (y = 1.0207 - 0.00374x). Most patients (81.6%) with 24-hour urine volumes of less than 2.1 had a urine specific gravity of more than 1.010. The use of specific gravity dipsticks was evaluated as a tool to help 24 patients increase the 24 hour urine volume. The 24-hour urine volume increased significantly (p less than 0.05, paired Student's t test) in patients after feedback from specific gravity dipsticks when they were instructed to keep the urine specific gravity at or less than 1.010 (average 24-hour urine volume increased 192%). We conclude that dietary advice may be insufficient to modify fluid intake habits in stone patients. However, modifications of fluid intake habits may be improved by feedback from specific gravity dipsticks. PMID- 1942322 TI - Metabolic evaluation in stone patients in relation to extracorporeal shock wave lithotripsy treatment. AB - No information exists in the literature about the optimal time for metabolic evaluation of stone patients in relation to extracorporeal shock wave lithotripsy (ESWL) treatment. It is uncertain whether the presence of a stone, ESWL treatment itself or subsequent colic episodes influence the urinary risk factors. A prospective study was performed to determine the optimal period for metabolic evaluation. Two 24-hour urine samples were collected directly before, and 1 week, 1 month and 3 months after therapy in an outpatient setting and tested for total volume, calcium, uric acid, oxalate, citrate and creatinine levels. A total of 66 patients was available for evaluation. Comparison of the 4 subsequent collecting periods showed no statistically significant differences in the excretion values. Also, in subgroups of patients with colic (16%), on a calcium oxalate restricted diet (12%) and with repeated treatments within 3 months (33%) no differences were noted. This means that the presence of a stone, treatment itself or subsequent colic episodes have no adverse effect on the urinary risk factors. For practical reasons metabolic evaluation directly before ESWL treatment seems most attractive. In the pre-ESWL samples hypercalciuria (greater than 7.5 mmol./24 hours), hyperuricosuria (greater than 6 mmol./24 hours), hyperoxaluria (greater than 0.5 mmol./24 hours) and hypocitraturia (less than 2 mmol./24 hours) were found in 31%, 12%, 18% and 27%, respectively, of the patients. It is concluded that metabolic evaluation before ESWL is practical, applicable and reliable. PMID- 1942323 TI - Extracorporeal shock wave lithotripsy for urinary tract stones using MPL 9000 spark gap technology and ultrasound monitoring. AB - Between November 7, 1988 and December 31, 1989, 881 treatments were given with the MPL 9000 lithotriptor to 513 sites in 510 renal units in 464 patients. Of the stones 447 (87.1%) were in the kidney, 64 (12.5%) in the ureter and 2 (0.4%) in the bladder. Stone size was up to 2 cm. in 58.5% of the cases, greater than 2 to 3 cm. in 25.8% and more than 3 cm. in 15.7%, including complete or partial staghorn, or multiple stones. Of the patients 54.2% received only 1 treatment, 17.6% received 2 treatments and 28.2% received more than 2 treatments (re treatment was necessary in 45.8%). The number of shocks used varied from 610 to 4,000 at 14 to 24 kv., the usual energy used being 18 kv. Of the stones 30.2% were treated after Double-J stents were inserted. A patient was declared stone free only when no stone particle was visible on a plain abdominal x-ray (or ultrasound if the stone was radiolucent). X-rays 3 months after extracorporeal shock wave lithotripsy (ESWL) were available for review in 397 patients (79.9%) and 72.8% were stone-free (with the aforementioned criteria) at 6 months (61.5% without ancillary procedures and 11.3% after ancillary procedures). Of a subset of 106 patients 84% were stone-free within 3 months when ESWL was restricted to a smaller stone burden, the number of shock waves administered was increased and energy was restricted to 14 to 18 kv. Over-all, 9.1% of the patients needed ancillary measures, including percutaneous nephrostomy in 1.6%, push-back for ESWL in 1.9%, ureterorenoscopy in 5.4%, percutaneous nephrolithotomy in 0.6% and pyelolithotomy/ureterolithotomy in 2.8%. The MPL 9000 device has the unique combination of electrohydraulic shock wave generation and ultrasound monitoring. The latter attribute has the distinct advantage of avoiding radiation to allow for visualization of nonopaque renal and gallbladder calculi. In addition, because there is continuous stone visualization during fragmentation accurate stone targeting can be maintained. The combination of ultrasound monitoring and spark gap technology allows for effective stone fragmentation. PMID- 1942324 TI - Polyurethane internal ureteral stents in treatment of stone patients: morbidity related to indwelling times. AB - The morbidity and complications associated with use of internal polyurethane ureteral stents in a series of 290 stone patients treated endourologically or with extracorporeal shock wave lithotripsy were retrospectively reviewed. Of the 299 stents retrieved 141 were also tested for patency to relate the rate of luminal blockage with stent caliber, indwelling time and clinical evidence of obstruction in the stented tract. Stent indwelling times ranged from a few days to 18 months: 11.3% were indwelling longer than 6 months and 1.9% were lost to followup. Incrustation occurred in 9.2% of the stents retrieved before 6 weeks, 47.5% indwelling 6 to 12 weeks and 76.3% thereafter. In 19 cases over-all (6.4%) an auxiliary procedure was required to decrease incrusted stone burden and enable stent retrieval. Other complications included stent migration (3.7%), infection (6.7%) and breakage (0.3%). Despite a 30% rate of luminal blockage in stents retrieved after indwelling times up to 3 months, the incidence of clinical obstruction in stented tracts up to 3 months was 4%, confirming other reports that significant urine flow occurs around rather than through hollow, vented stents. Our findings underline the importance of restricting the use of stents to stone patients who will be reliable at followup. Morbidity was minimal if stent indwelling times did not exceed 6 weeks. PMID- 1942325 TI - Endopyelotomy: review of results and complications. AB - Percutaneous endopyelotomy augmented by balloon dilation was performed on 27 of 40 patients for the treatment of symptomatic, primary ureteropelvic junction obstruction. Percutaneous ultrasonic lithotripsy was performed simultaneously on 12 of 27 patients (44%) for associated calculi. After endopyelotomy 24 of 27 patients became asymptomatic (clinical success rate 89%). Three clinically improved patients demonstrated only radiographic stability, while radiographic improvement was documented in 21 of 27 (radiographic success rate 78%). Adjuvant percutaneous ultrasonic lithotripsy was successful from the standpoint of stone removal in all patients and no increased morbidity could be identified. Of 27 patients 3 (11%) suffered major complications and are considered failures. Reasons for failure varied and are discussed. Included is a patient who at nephrostography and stent capping became septic and subsequently died. To decrease the risk of sepsis perioperative antibiotics to include at the time of nephrostomy tube capping are recommended. Angiography was performed in 19 of 40 patients to rule out an accessory crossing vessel at the ureteropelvic junction, and such a vessel was found in 6. From analysis of presenting excretory urograms (IVPs) we conclude that a crossing vessel cannot predictably be identified on an IVP. PMID- 1942326 TI - A simplified technique for continent urinary diversion: an all-stapled colonic reservoir. AB - A simple continent colonic reservoir was constructed in its entirety with the aid of surgical stapling techniques in 17 men and 10 women. In 5 men an orthotopic pouch was created and in the rest a continent stoma was designed. Detubularization of the entire colonic segment assures a low pressure system with disruption of directional peristaltic activity. The ureters are implanted by simply burying them in a mucosal furrow. Operative time required for the creation of the reservoir (excluding time for cystectomy) has ranged between 70 and 140 minutes (mean 95.4 minutes). With a followup of 9 to 60 months (mean 22.8 months) continence has been achieved in all but 1 patient with no ureteral reflux or obstruction. Urodynamically the pouch has achieved a large capacity (mean 750 cc) with low filling pressures (8.1 cm. water) because of technical ease of construction together with a shortened operative time due to the stapling techniques. This form of bladder replacement offers an option for select patients in whom continent urinary diversion is contemplated. PMID- 1942327 TI - Computerized tomography for detection and staging of localized and pathologically defined upper tract urothelial tumors. AB - Between 1980 and 1989, 94 patients were evaluated for upper tract urothelial tumors. Preoperative computerized tomography (CT) scans and pathology reports were available in 30 patients who also had nephroureterectomy for treatment of transitional cell carcinoma. Retrospective evaluation of these CT scans was done without knowledge of the final pathological status to determine accuracy of tumor detection and staging. Pathological findings were also reviewed and the pathological staging was compared to that of CT. At pathological evaluation the 30 renal units contained 34 grossly visible, distinct papillary tumors: 7 were ureteral and 27 were in the renal pelvis. Of the renal units 8 also contained carcinoma in situ that was not visible on any study. Conventional excretory urograms and/or retrograde or antegrade pyelograms detected 28 (82%) and CT 17 (50%) of the 34 papillary tumors. Excluding suboptimal scans due to early generation machines, inadequate intravenous contrast medium or too widely spaced slices caused CT sensitivity to increase to 15 of 22 (68%). It was not possible to distinguish stages Ta to T2 lesions on any radiological study. CT sensitivity for parenchymal invasion was 75% with a specificity of 43%. CT sensitivity for fat invasion was 67% with a specificity of 44%. We conclude that CT is limited in usefulness for detection and staging of low stage upper tract urothelial tumors. While CT is the best current imaging modality over-all for staging of upper tract urothelial tumors, results obtained in low stage tumors must be viewed with caution particularly when precise preoperative clinical staging is essential, such as before nephron-sparing procedures. PMID- 1942328 TI - Clinical study on urothelial tumors of dye workers in Wakayama City. AB - Between January 1951 and December 31, 1990 urothelial tumors were detected in 112 of 1,085 male dye workers (10.3%) in Wakayama City who were formerly engaged in manufacturing of benzidine and/or beta-naphthylamine. The period from exposure to the chemicals to development of the tumor was a mean of 24.1 +/- 9.4 years. A peak incidence of urothelial tumors was observed also approximately 25 years after the peak period of manufacturing these intermediate products of dyes. The mean period from exposure to such carcinogenic chemicals to the onset of the disease was estimated to be 25 years. Of the 78 patients with primary bladder cancer diagnosed since 1969, 43 (55.1%) had tumors diagnosed mostly as a result of a positive urinary cytology test obtained as part of a screening program and 35 (44.9%) had tumors diagnosed as the result of symptoms. Ten patients (24.4%) in the screened group had been treated with total cystectomy by the last followup examination compared with 17 (50.0%) in the symptomatic group. The 10-year cumulative survival rates were significantly (p less than 0.05) higher in the screened patients (75.1%) than in the symptomatic patients (55.1%). Our results indicate that screening of high risk populations with urinary cytology tests is effective for early diagnosis and treatment of urothelial tumors, and it improves patient prognosis. Furthermore, the biological behavior of occupational urothelial tumors may be different from that of urothelial tumors in the general population. PMID- 1942329 TI - Phase 1/2 study of intravesical epirubicin in patients with carcinoma in situ of the bladder. AB - A total of 34 patients with grade 3 carcinoma in situ of the bladder entered a phase 1/2 study with epirubicin to examine the rate of antitumor activity, the type and frequency of local side effects, and the absorption and recovery rates. The selected doses were 30, 50 and 80 mg. Of the patients 22 were evaluable for report of treatment results. A total of 16 patients had a complete remission proved by biopsy and conversion of urine cytology findings. Mean duration of complete remission was 22.4 months (range 7+ to 50+ months). After a mean followup of 35.3 months (range 14 to 59 months) 8 of 16 patients were still in complete remission, 3 died of a myocardial infarction, 3 had recurrent grade 3 carcinoma in situ, 2 had increase to a higher T category (stages T2 and T4a), and 2 had recurrent papillary stage Ta, grade 2 (1) and stage T1, grade 2 (1) transitional cell carcinoma of the bladder. Six of the 22 patients had no response to 1 or 2 treatment courses with a higher dose. Plasma concentrations of epirubicin after instillation were close to the detection limit of the assay (0.5 to 2.0 ng/ml. plasma). PMID- 1942330 TI - Intravesical bacillus Calmette-Guerin or mitomycin C in the treatment of carcinoma in situ of the bladder following prior pelvic radiation therapy. AB - A total of 20 patients received intravesical bacillus Calmette-Guerin (BCG) or mitomycin C for the treatment of carcinoma in situ following previous pelvic radiation therapy. Of the patients 14 (70%) responded completely after 1 or 2 courses of intravesical therapy. Mean followup from diagnosis of carcinoma in situ currently is 15.7 months. Complications of BCG and mitomycin C therapy were compared to the established complications of intravesical therapy with these agents. The incidences of fever greater than 103F, hematuria and bladder contracture were increased in patients receiving BCG following radiation therapy, although the cause of bladder contracture was probably multifactorial in our patient population. Our data suggest that BCG and mitomycin C are safe and biologically effective agents for the intravesical treatment of carcinoma in situ after pelvic radiation therapy. PMID- 1942331 TI - Immunohistochemical localization of metallothionein in transitional cell carcinoma of the bladder. AB - Metallothionein is a metal binding protein thiol found in high concentrations in the liver and kidney. Recent evidence has linked overexpression of cellular metallothionein with tumor cell resistance to chemotherapeutic drugs, such as alkylating agents and cis-diamminedichloroplatinum (II) (cisplatin). We studied the metallothionein content of 9 human transitional cell carcinomas of the bladder with immunohistochemical methods. All tumors stained positive for metallothionein and the staining was localized almost exclusively to the cytoplasm. Uroepithelium displaying dysplastic changes or carcinoma in situ demonstrated the greatest intensity of staining, while staining in the invasive portions of the tumor was weak and variable. These findings were of interest, since combination chemotherapy of invasive transitional cell carcinoma of the bladder often is ineffective against carcinoma in situ. Normal uroepithelium stained strongly in all 3 patients who experienced disease progression and death, and in only 1 of the 5 who are currently without evidence of disease. PMID- 1942332 TI - Monoclonal antibody Due ABC 3 directed against transitional cell carcinoma. II. Prospective trial on the diagnostic value of immunocytology using monoclonal antibody Due ABC 3. AB - Recently, the development of monoclonal antibody Due ABC 3 directed against transitional cell carcinoma has been reported. With this monoclonal antibody an in vitro test system for diagnosis and followup of patients with transitional cell carcinoma has been developed. The clinical value of this assay, designated as quantitative immunocytology, was evaluated in a prospective trial and compared to conventional cytology. We investigated 74 voided urine specimens obtained from patients with histologically proved transitional cell carcinoma and 60 specimens from donors without clinical evidence of transitional cell carcinoma. Sensitivity was 66% versus 47% for immunocytology and conventional cytology. Specificity of conventional cytology (92%) was higher compared to immunocytology (58%). Statistical analysis demonstrated a significantly higher sensitivity of the combined analysis of conventional cytology and immunocytology (p less than 0.001) compared to conventional cytology alone, without significant differences in specificity. The results obtained with immunocytology were impaired by the great number of nonevaluable specimens. Poor preservation of cells, severe pyuria or an insufficient number of urothelial cells prevented evaluation in 25% of the cases, while only 6% could not be evaluated by conventional cytology. The ability of immunocytology to improve the sensitivity of conventional cytology makes this technique a promising adjunct to the noninvasive diagnosis of transitional cell carcinoma. PMID- 1942333 TI - Identification of a high risk subgroup of grade 1 transitional cell carcinoma using image analysis based deoxyribonucleic acid ploidy analysis of tumor tissue. AB - The use of deoxyribonucleic acid (DNA) cytometry to identify a subset of patients with grade 1, stage Ta or T1 transitional cell carcinoma at high risk for death or recurrence was investigated in a retrospective study using paraffin blocks from 88 low grade transitional cell carcinomas of the bladder with an absorptiometric video-based image analysis system. Tumors were evaluated for ploidy (70 diploid, 16 aneuploid and 2 tetraploid) and the presence of cells with greater than 5C DNA. Survival analysis of 62 patients with adequate followup (15 to 20 years) showed that 43 of 62 (69%) suffered recurrences and 13 (21%) died of bladder cancer. The single most important predictors of death and recurrence were stem line aneuploidy and the presence of cells with greater than 5C DNA, respectively. PMID- 1942334 TI - Multivariate analysis of flow cytometric deoxyribonucleic acid parameters and histological features for prognosis of bladder cancer patients. AB - We studied whether flow cytometry provides significant prognosticators beyond the classical histological evaluation in the patient with bladder cancer. A total of 203 patients with untreated bladder cancer was evaluated using fresh bladder tumor specimens. Tumor grading and stage were the histological prognostic parameters. Deoxyribonucleic acid (DNA) index, percentage S-phase cells, percentage G2/M-phase cells and hypertetraploid cell presence were assessed as flow cytometric prognostic parameters. Multivariate survival analysis was performed using Cox's proportional regression model to study statistical individual prognostic values of histological and flow cytometric parameters. Hypertetraploid cell presence was the single most important prognostic factor (p less than 0.01), with tumor grade being nearly as important (p less than 0.01), followed by tetraploidy (p less than 0.01) and tumor stage (p less than 0.05). No other parameters, including the DNA index or cell phase fractions, contributed to the model. These results indicated that combined use of histological and flow cytometric parameters may provide additional information regarding the clinical outcome for bladder cancer patients. PMID- 1942335 TI - Prognosis of transitional cell bladder cancer: a multivariate prognostic score for improved prediction. AB - Clinical and histological prognostic factors were evaluated by means of Cox's analysis in 265 bladder cancer patients with a mean followup of 10 years. The parameters studied were obtained from the primary biopsies, which included clinical stage, World Health Organization grade, papillary status, morphometrically measured mean nuclear area, standard deviation of nuclear area, mean nuclear area of the 10 largest nuclei, mitotic activity index and volume corrected mitotic index. In univariate survival analysis all of the parameters predicted survival (p less than 0.001). In Cox's analysis the clinical stage was the most important prognosticator (p less than 0.001) followed by papillary status (p less than 0.001), volume corrected mitotic index (p = 0.011) and nuclear area of the 10 largest nuclei (p = 0.091). In stages Ta to T2, grades 1 to 2 tumors the papillary status (p = 0.001), mitotic activity index (p = 0.021) and T category (p = 0.029) showed independent prognostic value. Among the stages Ta to T1 tumors the papillary status included all of the available prognostic information (p = 0.001). In a separate analysis of histological features in all papillary tumors histological grade (p less than 0.001) and mitotic activity index (p = 0.021) were related independently to survival in Cox's analysis. In papillary stages Ta to T2, grades 1 to 2 tumors (mitotic activity index, p = 0.029) and in papillary stages Ta to T1 tumors (volume corrected mitotic index, p = 0.054) mitotic indexes showed independent prognostic value. In grade 2 tumors the papillary status p = 0.004) and mitotic activity index (p = 0.090) had independent prognostic value. The mitotic indexes predicted progression among stages Ta to T1 tumors (p less than 0.001) and within World Health Organization grades significantly. The combination of prognostic parameters into prognostic scores gave a more accurate estimate of survival than the single parameter approach. The results suggest morphometric grading of bladder tumors. However, papillary and nonpapillary tumors require different grade limits. PMID- 1942336 TI - Integral laser photodynamic treatment of refractory multifocal bladder tumors. AB - Integral photodynamic therapy with hematoporphyrin derivative was performed on 35 patients who had resistant transitional cell carcinoma of the bladder, mainly carcinoma in situ. The light source was an argon ion pumped dye laser (wavelength 630 nm.) using rhodamine B. Two types of laser light scattering diffuser developed at our department were used: a motor driven laser light scattering diffuser with computer regulation, and an endoscope modified light scattering diffuser tipped with a small quartz bulb containing a lipid nutritious solution as the scattering medium. The total energy density used was 10 to 30 J./cm.2. Of the 35 patients 24 (68.6%) achieved a complete response and 5 (14.3%) a partial response at 3 months. In 10 of the 24 patients there was no recurrence with an average tumor-free interval of 20.9 +/- 16.7 months, ranging from 5 to 60 months. Bladder capacity was decreased to approximately 150 ml. for 3 months after the integral photodynamic therapy without any evidence of hydronephrosis on excretory urograms, except for 2 patients who had a contracted bladder before photodynamic therapy. Integral photodynamic therapy may prove to be useful for the treatment of carcinoma in situ of the bladder. PMID- 1942337 TI - Proposed new method for nonoperative treatment of urethral stones. AB - Urethral calculi is a common clinical problem in the Middle and Far East. Different endoscopic and operative techniques have been used in the treatment of impacted urethral stones. We report a noninvasive procedure to treat this condition. Intraurethral instillation of 2% lidocaine jelly was followed by spontaneous expulsion of the stone in 14 of 18 patients. The indications and limitations of the method are outlined. PMID- 1942338 TI - Primary endoscopic realignment following posterior urethral disruption. AB - We describe 5 cases in which complete posterior urethral disruption associated with pelvic fracture was managed by primary endoscopic realignment 7 to 19 days after injury. Realignment was accomplished using a flexible endoscope through the suprapubic tract and a rigid or flexible cystoscope in the distal urethra. A guide wire was passed from the suprapubic tract through the disrupted membranous urethra and out the distal urethra. A Councill catheter was left indwelling for 5 to 10 weeks. After removal a program of intermittent self-catheterization was continued for 3 months. Excellent results were obtained in 4 patients who are continent, including 2 who are potent. This technique allows considerable reduction of patient morbidity without compromising formal urethroplasty should it later be required. PMID- 1942339 TI - Transitional cell carcinoma of the urethra in men following cystectomy for bladder cancer: multivariate analysis for risk factors. AB - Multicentric development of transitional cell carcinoma in the urinary tract is well recognized. Of 169 male patients who underwent cystectomy for bladder cancer 18 (10.6%) demonstrated urethral cancer (all within 5 years after cystectomy). The risk factors involved in transitional cell carcinoma in regard to the occurrence of urethral cancer after cystectomy were examined by multivariate analysis. Characteristic patterns of bladder cancer in the cystectomy specimens were expressed by the grade, stage, number, size, location and gross pattern of the tumors. Significant risk factors in bladder cancer relating to the development of cancer in the retained urethra were papillary cancer, multiple cancers, and tumors in the bladder neck, prostatic urethra and prostatic gland. Among 19 patients with concomitant carcinoma in situ and/or multiple papillary tumors in the bladder who underwent simultaneous prophylactic urethrectomy with cystectomy in the same observed period 17 (89%) had no lesion in the resected urethra. The results of the multivariate analysis will be useful to avoid unnecessary prophylactic urethrectomy at cystectomy. However, further analysis and consideration of possible mechanisms of the secondary urethral cancer will be necessary to explain the discrepancy posed in the latter study involving 19 patients. PMID- 1942340 TI - Application of transrectal ultrasonography in modified Stamey procedure for stress urinary incontinence. AB - From June 1989 to August 1990, 21 women with genuine stress urinary incontinence were treated with the Gittes procedure combined with transrectal ultrasonography. The urethrovesical junction was well pinpointed on an ultrasonographic image. The strength of suspension providing the optimal posterior urethrovesical angle was changed by each patient. Posterior urethrovesical angles averaged 89.3 +/- 9.5 degrees at operation and 93.6 +/- 9.5 degrees (mean +/- standard deviation) on a postoperative lateral cystourethrogram with the patient straining while in the standing position. An indwelling urethral catheter was removed on postoperative day 1. None of the patients had residual urine of more than 50 ml. by 4 days postoperatively. Furthermore, the average maximum urinary flow rates significantly increased from 21.0 +/- 7.1 ml. per second preoperatively to 26.1 +/- 9.8 ml. per second postoperatively (p less than 0.01). Therefore, application of ultrasonography during bladder neck suspension is simple and reliable for determination of the optimal suspension as well as identification of the suspension site. PMID- 1942341 TI - The predictive significance of patient-reported sexual functioning in RigiScan sleep evaluations. AB - We evaluated the relevance of patient reported sex history information in predicting erectile functioning as measured by the RigiScan monitor. A total of 46 male veterans who presented with erectile dysfunction completed an extensive medical and psychological evaluation including a sexual history, and then underwent 2 consecutive nights of inhospital RigiScan sleep evaluation performed under supervision. Multivariate analyses indicated a significant relationship among patient reported sex history information, and RigiScan measurements of tip and base duration, and rigidity. The sex history item with the greatest predictive power was the question regarding early morning erections. The results of this study highlight the importance of patient reported information, and the significance of obtaining a detailed sex history in the evaluation of older, primarily chronically ill patients who present with erectile dysfunction. PMID- 1942342 TI - Risks of blood volume changes in hypogonadal men treated with testosterone enanthate for erectile impotence. AB - Administration of anabolic steroids carries many risks. We present a series of 15 patients with primary hypogonadism who as a group had statistically significant increases in whole body hematocrit and red blood cell volume while on testosterone therapy of 300 mg. intramuscularly every 3 weeks. A small decrease in plasma volume over-all was not significant. Subsequent analyses compared subgroups whose whole body hematocrit during testosterone therapy was either 48% or greater (9) or less than 48% (6). Interaction effects indicated that the subgroups were similar when off testosterone but when on testosterone the former group exhibited an increase in red blood cell volume and a decrease in plasma volume, while the latter group had little change in either measurement. Subsequent to stopping testosterone therapy 2 patients in the whole body hematocrit 48% or greater group suffered strokes and 1 had transient ischemic attacks while on therapy. No one in the whole body hematocrit less than 48% group has had any cerebrovascular symptoms. Clinical implications, as well as cost effective and practical suggestions for detecting possible dangerous hemoconcentration are discussed. PMID- 1942343 TI - Chronic orchialgia in the pain prone patient: the clinical perspective. AB - Chronic pain syndromes are well known to the medical community. The incidence of chronic pain syndromes and cost of evaluating these patients are rapidly increasing. Chronic testicular pain is a fairly common manifestation of a chronic pain syndrome. Retrospectively, we reviewed the records of 48 patients with chronic testicular or scrotal pain (greater than 6 months) evaluated at our institution during the last 7 years. These patients had multiple diagnostic and interventional procedures with few positive findings. There was little improvement in these patients after multiple surgical procedures. Based on the paucity of objective clinical findings a carefully directed diagnostic evaluation for orchialgia is outlined. The treatment of these patients is best managed by a multidisciplinary approach involving the urologist and a pain clinic environment. We believe that extensive diagnostic testing is not indicated in the absence of clinical findings and may serve to worsen the condition or lead to iatrogenic injury. Surgical intervention should be limited to cases when a clear indication is present. PMID- 1942344 TI - Polytetrafluoroethylene injection for post-prostatectomy incontinence: experience with 20 patients during 3 years. AB - We treated 20 men who were incontinent after prostatectomy and who had failed sphincter exercises with periurethral polytetrafluoroethylene (Teflon or Polytef) injections. Injections were done with the patient under brief general or spinal anesthesia as an outpatient or during a 24-hour hospitalization. Incontinence was due to radical prostatectomy in 17 patients and simple prostatectomy for benign disease in 3. Most patients had more than 1 injection and mean followup was 17 months. Of the 20 men 7 (35%) reported long-term improvement and 4 (20%) recommend the procedure to others. Complications were limited to 1 spontaneously resolving 48-hour bout of urinary retention and 1 episode of perineal polytetrafluoroethylene migration that produced pain for 3 months. We found the procedure to be simple, generally well tolerated and capable of producing clinical improvement in a significant minority of patients in whom it was used. PMID- 1942345 TI - The frequency and morbidity of local tumor recurrence after definitive radiotherapy for stage C prostate cancer. AB - Radiotherapy is reported to provide good control of locally advanced prostate cancer. However, few long-term studies have assessed the morbidity related to local tumor recurrence in patients treated with radiotherapy alone (without hormonal manipulation). To determine the frequency and severity of morbidity related to local recurrence we reviewed the course of all patients with clinical stage C prostate cancer treated at our institution between 1966 and 1979 with bilateral pelvic lymph node dissection, radioactive gold seed implantation and external beam irradiation therapy to the prostate. Of the 121 patients 60% died and the 40% still alive at the time of review were followed for a mean of 8.1 years (range 3.3 to 14.8 years). Over-all, 64 patients (53%) had local recurrence, which was defined as a clinical event causing signs or symptoms and was proved by biopsy. On an actuarial basis the risk of local recurrence was 43 +/- 10% (mean +/- 2 standard errors) at 5 years and 74 +/- 11% at 10 years. Any symptomatic episode requiring active intervention or causing morbidity was denoted an adverse event. There were 162 adverse events among the 73 patients (2.2 adverse events per patient): 69% of these were severe (requiring surgical intervention) and 55% were chronic (more than 3 months in duration). The most common cause of an adverse event was bladder outlet obstruction requiring transurethral resection of the prostate (44 patients); 16 patients (13%) became incontinent. Hydronephrosis developed in 24 patients (20%). Local recurrence after definitive radiotherapy for our patients with stage C prostate cancer was common and was associated with serious morbidity, frequently requiring surgical intervention. Radiotherapy alone may not be sufficient to provide long-term local control of stage C prostate cancer. PMID- 1942346 TI - Strategies for ureteral catheterization after antireflux surgery by the Cohen technique of transverse advancement. AB - The Cohen technique for antireflux surgery is well established and provides excellent results. A major drawback with this technique is the difficulty in catheterizing the ureter postoperatively. We describe different strategies that can be used to catheterize the ureter successfully. PMID- 1942347 TI - Renal transplantation in children with posterior urethral valves. AB - We compared retrospectively the outcome of renal transplantation in 18 children with a diagnosis of posterior urethral valves to 18 matched children with nonobstructed renal failure to identify the disadvantages of renal transplantation into the valve bladder. There was no statistical difference in patient survival. The 5-year graft survival rate was 62.3% in children with posterior urethral valves and 48% in the control group. The difference was not statistically significant (p = 0.32). A statistically significant increase in serum creatinine from 1.2 to 2.2 mg./dl. was noted in the patients with posterior urethral valves, which was not seen in the control group (p = 0.0009). The clinical significance of this finding is unknown. Renal transplantation can be performed successfully in patients with posterior urethral valves. A prospective study is required to determine the benefits of preoperative lower urinary tract urodynamic assessment and the true effect of the valve bladder. PMID- 1942348 TI - Primary renal lymphoma. AB - Lymphomatous involvement of the kidneys is a common manifestation of systemic non Hodgkin's lymphoma but associated renal dysfunction is uncommon. In contrast, lymphoma originating within the kidneys is a rare event. We report a case of primary renal lymphoma presenting with renal insufficiency and hypertension in a 10-year-old boy. PMID- 1942349 TI - Nonsurgical management of primary vesicoureteral reflux in complete ureteral duplication: is it justified? AB - We reviewed the treatment of 56 children with vesicoureteral reflux and complete duplication of the collecting system, including 14 who had complete bilateral duplication. A total of 70 refluxing duplicated systems was analyzed. Of the patients 18% demonstrated spontaneous resolution of reflux within 42 months, 23% are currently stable on prophylactic antibiotics and 57.1% underwent surgical correction. Spontaneous resolution of reflux occurred in 58% of the children with grades I to III/V reflux. In comparing the group with reflux and duplication to a group with reflux into single systems, we conclude that the patients with duplication and lower grades of reflux can be managed nonoperatively, while infection is prevented with antibiotic prophylaxis. PMID- 1942350 TI - Granular cell tumor of the corpus cavernosum of the penis. PMID- 1942351 TI - Autonomic hyperreflexia in spinal cord injury patient during percutaneous nephrolithotomy for renal stone: a case report. AB - Autonomic hyperreflexia or autonomic dysreflexia is a syndrome seen in approximately 85% of all quadriplegic patients and constitutes the only medical emergency related to spinal cord injury. We report on a paraplegic patient with a C5 to C7 spinal cord injury who suffered autonomic hyperreflexia during percutaneous nephrolithotomy for a right renal stone. The reflex-induced hypertension subsided with termination of the operation, and administration of an alpha and beta-adrenergic blocking agent (labelatol hydrochloride). The stone was removed successfully by pyelolithotomy with the patient under general anesthesia 4 days later. PMID- 1942352 TI - Xanthogranulomatous pyelonephritis and systemic amyloidosis: report of 2 new cases and the natural history of this association. AB - The association of xanthogranulomatous pyelonephritis and systemic amyloidosis is extremely rare. To our knowledge, despite innumerable cases of xanthogranulomatous pyelonephritis reported in the literature, this association has been described on only 2 occasions. Clinical, analytical and radiographic findings can be highly suggestive of the diagnosis. We report on 2 patients with xanthogranulomatous pyelonephritis, systemic amyloidosis and the nephrotic syndrome: 1 died 4 1/2 years after diagnosis and 1 was stable with good general health 3 years after diagnosis. The clinical aspects as well as the treatment given to both patients are discussed. We describe the natural history of an association that due to its rarity is not currently well known. PMID- 1942353 TI - Renin-secreting juxtaglomerular tumor causing severe hypertension: diagnosis by computerized tomography-directed needle biopsy. AB - Renin-secreting tumors are a rare cause of severe hypertension accompanied by hypokalemia. Typically, these tumors have been difficult to diagnose preoperatively by standard radiographic and hormonal studies. We describe a 44 year-old man who was hospitalized for paroxysmal hypertension and who had a 2.3 cm. mid upper pole renal mass on sonography. Computerized tomography-directed needle biopsy revealed a juxtaglomerular tumor and surgical excision of the tumor was curative. We discuss the unique diagnostic aspects of this case. PMID- 1942354 TI - Acute renal failure secondary to carcinomatous lymphatic metastases to kidneys. AB - We report a rare case of acute renal failure secondary to bilateral renal parenchymal metastases from carcinoma. Despite clinical investigation the cause of the renal failure remained undiagnosed and was discovered only upon microscopy at autopsy, which revealed metastatic gastric adenocarcinoma. The pattern of tumor infiltration was predominantly lymphatic involvement limited to the vascular bundles at the corticomedullary junction, and the lymphatics adjacent to the calices and pelves. The significance of lymphatic obstruction in the pathogenesis of renal failure is discussed. Renal parenchymal metastases should be considered in the differential diagnosis of acute renal failure in patients with carcinoma. PMID- 1942355 TI - Polyclonal B cell lymphoma of renal transplant ureter induced by cyclosporine: case report. AB - A case of a renal transplant patient who had polyclonal B cell lymphoma of the transplant ureter 3 months postoperatively while on cyclosporine therapy is reported. Removal of the ureteral segment along with acyclovir therapy and discontinuation of cyclosporine resulted in no subsequent tumor growth and stable renal function for more than 5 years. PMID- 1942356 TI - Posterior urethroplasty with tubularized bladder mucosal graft. AB - Surgical management of long strictures of the posterior urethra is difficult and there is no concrete method that guarantees excellent results. The use of bladder mucosa has become established in the 1980s as treatment for anterior urethral reconstruction in hypospadias repair. We report 2 difficult cases (multioperations) of membranous urethral strictures treated with free tubularized bladder mucosal grafts with good initial results. PMID- 1942357 TI - Re: Extracorporeal shock wave lithotripsy in patients with bleeding diatheses. PMID- 1942358 TI - Re: Incidence and properties of renal masses and asymptomatic renal cell carcinoma detected by abdominal ultrasonography. PMID- 1942359 TI - Re: Skin necrosis caused by use of negative pressure device for erectile impotence. PMID- 1942360 TI - Re: Uncircumcision: a technique for plastic reconstruction of a prepuce after circumcision. PMID- 1942361 TI - Anemia in new congenital adult type polycystic kidney mice. AB - Mechanisms for the development of anemia and the effects of recombinant human erythropoietin (r-HuEPO) on hematological parameters were studied in new congenital adult type polycystic kidney (DBA/2FG-pcy) mice. The majority of DBA/2FG-pcy mice showed progressive anemia and an elevation of blood urea nitrogen, while a minority showed progressive anemia following polycythemia. Kidneys with numerous cysts in the cortex and medulla occupied virtually the entire abdominal cavity, and the combined kidney weight taken as a percentage of body weight reached 13.5% in the DBA/2FG-pcy mouse. The osmotic fragility of DBA/2FG-pcy mice erythrocytes was significantly increased compared with that of normal control mice. In addition, two-fold increases in serum EPO levels, determined by radioimmunoassay, and a decreased number of colony forming unit erythroid (CFU-E) were observed in the DBA/2FG-pcy mice. The administration of r HuEPO during anemia significantly increased the red blood cell count, hemoglobin concentration, hematocrit and reticulocyte percentage in a dose-dependent manner. These findings indicate that anemia in the DBA/2FG-pcy mouse is due to increased fragility of erythrocytes, a deficiency in EPO for the degree of anemia and a decreased number or a decreased response of erythroid progenitor cells. We suggest that the DBA/2FG-pcy mouse is a useful spontaneous model of chronic progressive renal failure. PMID- 1942362 TI - Free and conjugated chlorin E6 in the photodynamic therapy of human bladder carcinoma cells. AB - Photodynamic therapy is an experimental modality for treatment of superficial bladder cancer, and consists of the administration of a photosensitizer and subsequent tumor-irradiation with light. Presently hematoporphyrin derivative (HPD) is the only photosensitizer in experimental clinical use in the United States. Because of the high nonspecific phototoxicity of HPD, new methods of photosensitization have been sought. In this study we compared chlorin e6, free and conjugated to 1-micron.-diameter latex microspheres. Phototoxicity was evaluated on MGH-U1 cells derived from a human bladder carcinoma. MGH-U1 cells were preincubated for 18 hours either with free Ce6 (0.43 microM) or Ce6 microspheres (0.43 microM equivalent in Ce6) and irradiated with an argon-laser pumped dye laser emitting at 659 nm., over the radiant-exposure range of 5-50 J/cm. At 24 hours after light exposure the cells were observed microscopically for morphological alteration and evaluated for cell death by trypan blue exclusion. Cultures incubated with Ce6-microspheres and subsequently irradiated showed morphologic evidence of cell damage, apparent after irradiation with five J/cm. and a light dose dependent decrease in cell survival. In contrast, cells incubated with free Ce6 at the same concentration of 0.43 microM and subsequently irradiated demonstrated neither detectable morphologic alteration nor change in cell survival. Only cells preincubated with free Ce6 at higher concentration showed morphologic changes. Thus, Ce6-microsphere conjugate was much more efficient at inducing photodynamic destruction of bladder carcinoma cells than was free Ce6. PMID- 1942363 TI - Oral and intravaginal estrogens alone and in combination with alpha-adrenergic stimulation in genuine stress incontinence. PMID- 1942364 TI - Crossroads. PMID- 1942365 TI - Venous valvular insufficiency: influence of a single venous valve (native and experimental). AB - This report evaluates the ability of a single competent (native or experimental) superficial femoral vein valve to correct canine hindlimb venous insufficiency. The time to maximal ankle venous pressure after standing (VFT) and to 90% of that time after exercise (VRT90), and the minimal pressure after exercise (AVP) were measured in 17 greyhounds before intervention, after only the superficial femoral vein valve remained (n = 5), and after complete lower limb venous valvulotomy (n = 17). Three weeks later, 12 dogs underwent a native (n = 4) or experimental (n = 8) autogenous venous valve transplantation. Immediately and at 3 weeks after transplantation, venous pressure measurements were obtained. The manual strip test confirmed valve competence at the time of sacrifice. Only one valve transplant became incompetent. Immediately after single superficial femoral vein valve construction, VFT, AVP, and VRT90 measurements were not significantly different from normal. Three weeks after transplantation the AVP measurements were consistent with an insufficient venous system, whereas the VRT90 measurements were between and statistically different from both the control and totally incompetent system (p less than 0.05). After the native valve but not the experimental valve transplantations VFT normalized. These data suggest that insertion of a single competent superficial femoral vein valve into an incompetent lower limb venous system corrects venous pressure measurements initially but soon provides only a partially competent system. The experimental valve, although competent, is less responsive than a native valve. PMID- 1942366 TI - Deep venous thrombosis in the baboon: an experimental model. AB - Experimental models of deep venous thrombosis, heretofore, have not been available for laboratory studies. This investigation establishes a novel model of venous thrombosis by inhibiting the protein C system combined with venous stasis and subtle venous injury. Ten adolescent baboons were studied in pairs, with one animal receiving saline solution (B2, B4, B6, B8, B10) and one being exposed to thrombogenic reagents (B1, B3, B5, B7, B9). These reagents represented a combination of a monoclonal antibody (HPC4) to protein C, 1 to 4 mg/kg administered over 5 minutes, and tumor necrosis factor administered over 3 minutes at a dose of 150 micrograms/kg through a catheter placed into the left superficial femoral vein with distal ligation. To encourage stasis, a pediatric size blood pressure cuff was inflated to 40 mm Hg on the right thigh for 50 minutes of every hour during the first experimental day (day 1) in B5 to B10. The animals were observed for a 6-hour period on day 1 and then for an 11- to 15-day period until sacrifice. Hemodynamic and hematologic parameters were recorded along with duplex imaging of the iliac veins and inferior vena cava on a daily basis. Venography was performed on day 1, day 4, and the day of sacrifice. At sacrifice the entire iliac and vena caval system was carefully dissected, opened, and photographed. Experimental animals given the HPC4 and tumor necrosis factor developed left iliac vein thrombosis extending into the inferior vena cava. Duplex imaging, venography, and autopsy revealed that control animals receiving saline solution never developed comparable thrombus. Experimental subjects exhibited thrombus on duplex imaging by day 4 (B1), day 3 (B3), day 2 (B5), 120 minutes (B7), and 360 minutes (B9) after receiving HPC4 and tumor necrosis factor. Venograms performed on day 1 exhibited thrombus in B5, B7, and B9. The extent of thrombus, the timing of its occurrence, and its effect on the animals' left leg followed a dose-dependent relationship for the animals in which the occlusive blood pressure cuff was used. Significantly greater declines in blood pressure, white blood cell count, and platelet count were found in affected animals given HPC4 and tumor necrosis factor reagents as compared to control subjects. All affected animals demonstrated the appearance of fibrin split products and a markedly prolonged prothrombin time. This investigation, for the first time, establishes a reproducible model of deep venous thrombosis involving inhibition of protein C that will facilitate further laboratory studies on venous thrombosis. PMID- 1942367 TI - A comparison of CO2 laser-assisted venous anastomoses and conventional suture techniques: patency, aneurysm formation, and histologic differences. AB - The expected patency and the potential complications of CO2 laser-welded end-to end venous anastomoses have not been well established despite increasing clinical interest in the subject. To further study this relatively new technique we used the internal jugular veins (1.0 to 1.4 mm diameter) of 15 New Zealand White rabbits weighing 2.5 to 3.5 kg. On one randomly selected side, a laser-welded end to-end anastomosis was performed in all animals by placing three equidistant stay sutures followed by welding the vein edges with a CO2 laser (spot size of 0.27 mm, power of 100 mW, and power density of 175 W/cm2). On the contralateral side, the vein was anastomosed with interrupted 10-0 nylon sutures in 10 animals, and in the remaining five animals a continuous 10-0 nylon suture technique was used. All anastomoses were surgically assessed at 30 days after operation. A significantly lower 30-day patency rate (p less than 0.05, Fisher's Exact Test) was found in anastomoses constructed by use of the continuous technique (20%) compared with either interrupted (90%) or the laser-assisted technique (87%). No significant difference was observed in 30-day patency between laser-assisted and conventional interrupted anastomoses. Anastomoses performed with the continuous and the laser-assisted technique required 12.5 +/- 1.3 and 12.9 +/- 3.0 minutes, respectively, whereas those constructed with interrupted technique required 19.1 +/- 4.5 minutes (p less than 0.05, Student-Neuman-Keuls' Test). No evidence of false or true aneurysm was noted in any of the animals. Histologic evaluation of laser-assisted anastomoses demonstrated early full-thickness coagulation necrosis of the wall with reendothelialization by 7 days and complete healing by 30 days after the procedure. Conventional anastomoses showed reendothelialization and minimal necrosis near the sutures at 7 days, but healing was complete by 30 days after the procedure. The patency rate of vein anastomoses performed with the CO2 laser is excellent and superior to the one obtained with continuous sutures, and except for less operating time, the former technique does not appear to offer any significant advantage over the conventional interrupted suture technique for small vein anastomosis in this animal model up to 1 month of follow-up. PMID- 1942368 TI - Intracardiac and intrapulmonary Greenfield filters: a long-term follow-up. AB - The Greenfield vena caval filter has become the preferred method of vena caval filtration. Its high long-term patency rate and low complication rate make it ideal for those patients in whom anticoagulation has failed or is contraindicated. A known complication of filter insertion is the inadvertent placement or migration of the filter to the right side of the heart. We present three cases from our institution where the Greenfield filter was inadvertently ejected into the right atrium. An attempt at removal with a wire loop and sheath in two cases failed and resulted in the migration of one filter to the right inferior pulmonary artery. We found no evidence of long-term complications at 2, 45, and 60 months. We conclude that conservative management may be considered in these cases. PMID- 1942369 TI - Lower extremity calf thrombosis: to treat or not to treat? AB - Seventy-five patients with isolated calf vein thrombi were prospectively monitored with sequential duplex scans at 3- to 4-day intervals. Twenty-four patients (32%) propagated and 11 of these 24 (46%) into the popliteal or larger veins of the thigh. Sex, age, obesity, trauma, estrogen use, malignancy, varicose veins, smoking, surgery, and activity level were not predictive for proximal propagation. Proximal soleal vein thrombi had the highest incidence in both propagating and non-propagating groups. Thrombus extent and bilateral involvement were not predictive of propagation. Five percent (4 of 75 patients) had highly probable ventilation perfusion scans as their initial indication for duplex scanning. Deep vein thrombosis isolated to the calf is not a benign problem. If anticoagulant therapy is contraindicated, the progress of the thrombus can be followed by duplex scanning. PMID- 1942370 TI - Use of lower extremity deep veins as arterial substitutes: functional status of the donor leg. AB - Large veins (superior and inferior vena cava, portal vein) have been replaced successfully with lower extremity deep veins (superficial femoral-popliteal). Femoropopliteal bypass with superficial femoral-popliteal veins has been reported to give excellent long-term results. Nevertheless, this source of autogenous veins has not gained acceptance, in part because of the fear that deep vein removal will result in severe venous outflow restriction in the donor limb. To assess the clinical and functional effect of excising a deep vein, we compared a group of limbs in which the superficial femoral-popliteal vein was resected for use as a femoropopliteal bypass graft (25 legs) with a control group of 22 legs in which a saphenous vein or polytetrafluoroethylene graft was used for femoropopliteal bypass. No significant differences were found in age or sex distribution, time from surgery to the venous test, side of bypass, or the incidence of postoperative extremity swelling, either early or late. A mild but significant calf enlargement was observed in the deep vein group (p less than 0.05), and a pattern consistent with venous outflow obstruction was shown by plethysmography in 21 of 25 extremities (84%) in which a deep vein was used for femoropopliteal bypass but in only 11 of 22 (50%) control extremities (p less than 0.02). It is concluded that a lower extremity deep veins should be considered as a suitable replacement for a large vein or, when superficial vein is not available, as an infrainguinal arterial substitute. PMID- 1942371 TI - Low dose heparin therapy: in vitro verification of antithrombotic effect. AB - Low dose heparin therapy has been used routinely for prophylaxis of deep venous thrombosis, yet in vitro data regarding its antithrombotic effects are sparse. The effects of heparin on venous thrombus formation were studied in an in vitro perfusion system. Fresh blood collected from human volunteers was treated with varying heparin doses and perfused at a shear rate of 100 sec-1 over everted, injured porcine vein segments, simulating conditions in the venous circulation. Platelet and fibrin deposition were measured by use of indium 111 and iodine 125 radiolabels, respectively. The effects of heparin on the intrinsic coagulation cascade were monitored by the activated clotting time. Increasing doses of heparin resulted in significant reductions in fibrin and platelet deposition (ANOVA F = 2.67 and 3.17, respectively, p less than 0.05). At a dose of only 0.19 USP units/ml blood, equivalent to a 1000 unit bolus of heparin in a 70 kg man, a noticeable reduction in both fibrin and platelet deposition was observed without an increase in the activated clotting time. These data confirm the antithrombotic effects of heparin at low dose ranges and may explain the clinically observed phenomenon of deep venous prophylaxis without an appreciable alteration in the conventional coagulation assays. PMID- 1942372 TI - Clinical, hemodynamic, and anatomic predictors of long-term outcome of lower extremity venovenous bypasses. AB - Forty-three patients, 24 with crossover femoral saphenous vein bypasses and 19 with saphenopopliteal vein bypasses, were observed for a mean of 5.5 years. All underwent preoperative and sequential postoperative clinical, hemodynamic and foot venous pressure measurement, and anatomic evaluations (duplex and venography). Seventy-one percent of patients undergoing crossover femoral saphenous vein bypasses and 74% of patients undergoing saphenopopliteal vein bypasses had an abnormal preoperative maximum venous outflow, in contrast to 4% and 11% after operation (p = 0.0183). The mean immediate postoperative maximum venous outflow improvement for patients having crossover femoral saphenous vein bypasses and those having saphenopopliteal vein bypasses was 16 and 17 ml, respectively, and the mean late improvement was 19 and 27 ml, respectively. Ninety percent of the patients undergoing crossover femoral vein bypasses and those having saphenopopliteal vein bypasses had abnormal foot venous pressures in contrast to 18% and 22% after operation. The final clinical outcomes (over 1 year) for both patients having the crossover saphenous vein bypasses and those having saphenopopliteal vein bypasses, respectively, were significant improvement (+3 and +2), 63% and 58%; significant worsening (-2), 4% and 5%. Eighty-eight percent of patients undergoing crossover femoral saphenous vein bypasses and 79% of patients undergoing saphenopopliteal vein bypasses with abnormal preoperative maximum venous outflow measurements had significant clinical improvement. In contrast, 86% of patients undergoing crossover femoral saphenous vein bypasses and 80% of patients undergoing saphenopopliteal vein bypasses with normal preoperative maximum venous outflow had no improvement. Seventy-seven percent of patients having saphenopopliteal vein bypasses and a normal venous refill time had significant improvement, in contrast to 17% for patients with an abnormal venous refill time (less than 10 sec). Sixty-seven percent of patients undergoing crossover femoral saphenous vein bypasses and 78% of patients undergoing saphenopopliteal vein bypasses with abnormal foot venous pressure measurements had significant improvement. The cumulative 7-year patency was 75% for patients having crossover femoral saphenous vein bypasses and 56% for those having saphenopopliteal vein bypasses. The operative mortality rate was 0% for both procedures, and the complication rate was 4% and 10%, respectively. The most important preoperative variables that correlated with a good outcome were a low preoperative maximum venous outflow, venous refill time greater than 10 sec, and venous claudication and iliac vein compression. Patients with a normal maximum venous outflow measurement and severe venous reflux should not be candidates for these bypasses. PMID- 1942373 TI - Femoral vein valve repair under direct vision without venotomy: a modified technique with use of angioscopy. PMID- 1942374 TI - Measurement of blood flow rates in the lower extremities with use of a nuclear magnetic resonance based instrument. AB - Direct, noninvasive measurement of pulsatile blood flow to the human extremity is now possible by means of a flow measurement instrument that is based on the principles of nuclear magnetic resonance. The instrument uses a physically independent calibration module as a primary calibration standard. Volumetric calibration of this module indicates that it is precise and accurate over the range of 0 to 100 ml/min. The calibration module is used, in turn, to calibrate an electromagnetic flow sensor that is incorporated into the instrumentation. The calibration module and the electromagnetic sensor were found to be linearly related over the range of 5 to 100 ml/min, with a regression correlation coefficient of 0.996. The calibrated electromagnetic flow sensor is used as a secondary standard for calibration of the nuclear magnetic resonance sensor. Blood flow measurements, obtained by use of this method, agree closely with those obtained by plethysmographic methods. They differ from the plethysmographic results in that magnetic resonance flows will distinguish between the at-rest blood flow in the normal extremity and the flows seen in the extremity (also at rest) with claudication. Based on the results obtained from studying a limited number of limbs with a high degree of ischemia, the method will not distinguish the limb with ischemia from the limb with claudication. Limitations of the method and refinements required to make the method clinically useful are discussed. PMID- 1942375 TI - Computer simulation of blood flow patterns in arteries of various geometries. AB - The purpose of this study is to illustrate the application of computer simulation to the study of blood flow through arteries and to demonstrate the relationship between geometry of the vessels and local flow patterns. A finite element computer program was developed to simulate steady and pulsatile blood flow by solving the continuity and Navier-Stokes equations. The accuracy of the computational method has been confirmed by comparing the numeric results to analytic solutions and to published experimental data from physical models. The results are presented as plots of the velocity vectors, streamlines, and pressure contours. The computational model has been applied to illustrate flow patterns in the following situations: pulsatile flow in a cylindric artery and an artery with an axisymmetric stenosis, steady flow in cylindric arteries with stenoses of varying severity and with different flow rates, steady flow in an artery containing a fusiform aneurysm, steady flow in a two-dimensional model of a symmetric Y-shaped bifurcation, and steady flow in a two-dimensional model of the carotid bifurcation. Regions that are commonly associated with arterial disease often coincide with zones of reversed or stagnant flow. In conclusion, the versatility and feasibility of computational simulation of blood flow is illustrated by this study. Although this mathematic model is a simplification of the real flow phenomena, it yields results that provide useful insights into the understanding of local blood flow patterns for a variety of complex geometries. PMID- 1942376 TI - Cefamandole levels during thoracoabdominal aortic aneurysm surgery. AB - The pharmacokinetics of prophylactic antibodies may differ in cardiac and aortic aneurysm surgery for at least two reasons: aortic aneurysm surgery generally entails a greater blood volume loss and replacement, and aortic aneurysm surgery usually does not require extracorporeal cardiopulmonary bypass. We prospectively studied two different cefamandole dosing regimens in patients undergoing aortic aneurysm surgery (phase 1, 1 gm intravenously at the induction of anesthesia; phase 2, 2 gm intravenously at the induction of anesthesia followed by 1 gm intravenously every 2 hours during surgery). In phase 1 and 2 plasma levels were measured at the time of skin incision, aortic cross-clamping, aortic unclamping, and skin closure. In phase 2 cefamandole elimination in urine and cell-saver effluent was also determined. An adequate plasma level of 10 micrograms/ml was maintained in only 4 of 14 patients in phase 1, but in 10 of 10 patients in phase 2. Cefamandole loss in cell-saver effluent was 136 +/- 100 mg, which was 13% of the measured renally excreted amount. As has been previously shown in cardiac surgery, a cefamandole prophylactic antibiotic regimen of 2 gm intravenously at the induction of anesthesia followed by 1 gm every 2 hours during surgery provides a dependable and practical dosing regimen in patients undergoing aortic aneurysm surgery. PMID- 1942377 TI - Unilateral iliofemoral occlusive disease: long-term results of the semi-closed endarterectomy with the ring-stripper. AB - Nowadays, fewer endarterectomies are performed for treatment of occlusive arterial disease; more often a bypass procedure is done. This study investigates whether the results of the semiclosed endarterectomy for unilateral iliofemoral occlusive disease indeed indicate a wider use of bypass procedures for such short obstructions. Ninety-four patients with an obstructed external iliac and common femoral artery, but with patent ipsilateral common iliac and contralateral iliac arteries, underwent 101 operations. Seven of these patients were operated on at a later stage for occlusive disease on the contralateral side. Ninety-three endarterectomies were performed, and an iliofemoral bypass graft was inserted eight times because an endarterectomy was not feasible. Sixty-two operations were performed for disabling claudication, and 39 operations were performed for limb threatening ischemia. Eighty-five percent of the patients who underwent an endarterectomy for disabling claudication became asymptomatic. Eighty percent of the patients who underwent an endarterectomy for limb-threatening ischemia became asymptomatic or improved to claudication. After endarterectomy no deaths, false aneurysms, or infections occurred. The patency rates at 1, 5, and 10 years were 94%, 83%, and 65%, respectively. We conclude that the semiclosed endarterectomy with the ringstripper of a unilateral obstruction of one external iliac and common femoral artery can be performed with a low morbidity and without deaths and gives good long-term results. PMID- 1942378 TI - The valvular anatomy of the iliac venous system and its clinical implications. AB - Clinical and phlebographic evidence exists that correlates the presence of varices of the vulva, posterior thigh, and the pelvic congestion syndrome with insufficiency of the internal iliac venous system (pelvic dumping syndrome). Information in the modern medical literature regarding the valvular anatomy of the internal iliac veins and its tributaries is limited. We dissected 82 iliac venous system specimens in 42 human cadavers (29 men, 13 women) to gain information on the relationship between the disease described and the anatomy of the region. Each specimen contained common, external, and internal iliac veins, including the tributaries of the latter. We recorded the anatomic variations of the internal iliac vein trunk and the location of valves in the complete iliac venous system, including 485 tributaries of the internal iliac veins. Five specimens of internal iliac vein had calcified thrombosis or were extensively involved with pelvic carcinoma and were not suitable for valve study, which left 79 specimens for analysis. The internal iliac vein drained into the external iliac venous system by means of a single trunk in 73% of the specimens and by two well-formed and separated trunks in 27% of the specimens. In one specimen (1.2%) the internal iliac vein drained directly into the inferior vena cava (parallel internal and external iliac veins). One specimen had a well-developed valve in the common iliac vein (1.2%). The external iliac vein had one valve in 26.2% of the specimens. This vein had three times as many valves on the right side as in the left (39.6% vs 14.6%: p = 0.0106).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942379 TI - Urokinase treatment of neonatal aortoiliac thrombosis caused by umbilical artery catheterization: a case report. AB - Umbilical artery catheterization is known to be associated with aortoiliac thrombosis in approximately 1% of newborns in whom catheters are placed. We describe a case of catheter-associated aortoiliac thrombosis in a newborn who was successfully treated by urokinase infusion. The infant was monitored by imaging studies followed by ultrasonography. The use of real-time ultrasonography enabled us to image this infant's aortoiliac thrombosis in an accurate, noninvasive manner and monitor the effectiveness of thrombolytic therapy. The fibrinolytic state was achieved with a combination of intravenous and intraarterial infusions of urokinase. Frequent measurement of prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin time was used to guide fibrinolytic therapy. We reviewed the literature for similar cases of aortoiliac thrombosis in newborns; some were managed by medical means, others by operation. The success rate of the two approaches appeared to be approximately equal. Therefore we recommend the less invasive approach first--urokinase therapy--to be followed by surgical intervention if thrombolysis is unsuccessful. PMID- 1942381 TI - Blood flow measurement with nuclear magnetic resonance technology: a clinically applicable technique? PMID- 1942380 TI - Leiomyosarcoma of the inferior vena cava: analysis and search of world literature on 141 patients and report of three new cases. AB - Leiomyosarcoma of the inferior vena cava is a rare and potentially curable tumor. Uncertainty about the results of treatment derives from lack of a large series in the same center and of a long-term follow-up of the published cases. A review of the world literature from 1871 to 1989 allowed us to collect information on 141 patients with inferior vena cava leiomyosarcoma to which our three cases have to be added. The tumor arose from the lower segment of the inferior vena cava (infrarenal portion) in 49 patients, from the middle segment (from the renal veins to the hepatic veins) in 59, and from the upper segment (from the hepatic veins to the right atrium) in 34 patients. Complete clinical, pathologic, and therapeutic data and up-to-date follow-up have been obtained through personal correspondence with several authors. All data have been examined with both univariate and multivariate analyses as predictive factors for outcome. Variables, associated with an increased risk of death from disease, included the involvement of inferior vena cava upper segment and a high-grade tumor. Patients who underwent a radical resection of the tumor (82 patients, 56.9%) had a significantly better survival (27.9% and 14.2%, 5- and 10-year survival rates, respectively). Of these patients, those with tumor of the inferior vena cava middle segment fared better than those with lower segment tumor (5- and 10-year survival rates were 48.3% and 34.4%, respectively, for middle segment tumor and 9.3% and 0.0% for lower segment tumor). Variables associated with a good outcome and longer survival were the presence of abdominal pain and the absence of a palpable abdominal mass. Despite the high rate of recurrence (52.4% of patients undergoing radical operation; median time, 25 months), radical resection of inferior vena cava leiomyosarcoma is the only chance for a long-term cure. An earlier and more accurate preoperative diagnosis, by means of modern diagnostic techniques (echography, CT scanning, magnetic resonance imaging) will allow a higher rate of radical resection to be performed with an increase in patient survival. PMID- 1942382 TI - Diagnostic evaluation of radioimmunoscintigraphy (RIS) with use of iodine 123 labeled antibodies against human granulocytes (123I-anti-NCA95) for the detection of prosthetic vascular graft infection. PMID- 1942383 TI - Reported measles decline continues; research seeks to avert resurgence. PMID- 1942384 TI - Defensive biological warfare researchers prepare to counteract 'natural' enemies in battle, at home. PMID- 1942385 TI - Limb-lengthening technique increasingly used. PMID- 1942386 TI - AMA, joint commission urge physicians become part of solution to family violence epidemic. PMID- 1942387 TI - Archives of Family Medicine appears in 1992 as AMA's 10th scientific specialty journal. PMID- 1942388 TI - From the Food and Drug Administration. PMID- 1942389 TI - From the Centers for Disease Control. Chlorine gas toxicity from mixture of bleach with other cleaning products--California. PMID- 1942390 TI - From the Centers for Disease Control. Influenza activity--worldwide, 1990-91. PMID- 1942391 TI - A piece of my mind. The man who didn't know he had cancer. PMID- 1942392 TI - Should physicians treat patients who seek second opinions? PMID- 1942393 TI - Teenage pregnancy and educational opportunity. PMID- 1942394 TI - Removing the pH from pHysician pHrases. PMID- 1942395 TI - The mechanism of HIV infection in patients of the Florida dentist. PMID- 1942396 TI - Digoxin in congestive heart failure. PMID- 1942397 TI - Access to health care for the uninsured: the American Academy of Family Physicians. PMID- 1942398 TI - The supply of primary care physicians. PMID- 1942399 TI - Hemolytic disease of the newborn: lowest achievable incidence rates. PMID- 1942400 TI - Advance directives. PMID- 1942401 TI - Cost of and payment source for pelvic inflammatory disease. Trends and projections, 1983 through 2000. AB - Pelvic inflammatory disease (PID) and its sequelae affect millions of women in the United States at substantial costs. To estimate these total costs annually and to determine payment sources, we analyzed data from local, state, and national sources. Direct costs for PID and PID-associated ectopic pregnancy and infertility were estimated to be $2.7 billion, and indirect costs were estimated to be $1.5 billion, for a total cost of $4.2 billion in 1990. Overall, private insurance covered the largest portion of the direct costs of PID (41%), followed by public payment sources (30%). However, the proportion of payments made by private insurance appears to be decreasing, while that by public payment sources is increasing. In the year 2000, costs associated with PID are projected to approach $10 billion if the current PID incidence persists, with an increasing proportion of this expense burdening public institutions. Prevention of PID is needed both to reduce human suffering and to contain rising costs. PMID- 1942402 TI - Self-reported pelvic inflammatory disease in the United States, 1988. AB - OBJECTIVE: --To assess any changes in the characteristics of women with self reported pelvic inflammatory disease (PID) between 1982 and 1988 and to evaluate the role of additional behavioral factors. In 1982, PID was a frequent problem among American women of reproductive age, occurring in one in seven. It was also more common among older (greater than or equal to 30 years) than younger women, more common among blacks than among whites, and more common among formerly married women than among those currently married. DESIGN: --We analyzed data on self-reported PID from the cycle IV National Survey of Family Growth, conducted in 1988. SAMPLE: --The survey was conducted with a multistage probability sample of 8450 women. RESULTS: --The findings from 1982 were all replicated. Additional variables available in 1988 show that PID is more common among women with multiple (two or more) sexual partners (10% to 22%) compared with those with only one lifetime partner (7%) and among women who report a history of sexually transmitted disease (STD) (26%) compared with those with no STD history (10%). Controlling for other variables, age, race, vaginal douching, age at first intercourse, STD history, and number of lifetime partners emerged as independent predictors of self-reported PID among American women of reproductive age. CONCLUSION: --PID is still a widely prevalent condition among American women, PID is associated with a variety of risk factors for STD. Prevention of lower genital tract infection is crucial to avoiding PID and its sequelae. PMID- 1942403 TI - Preventing pelvic inflammatory disease. AB - Effective strategies for preventing pelvic inflammatory disease (PID) are crucial to protect women from adverse reproductive consequences and to avoid substantial economic losses. To identify current PID prevention options and assess their efficacy, we conducted a literature search and examined relevant data in published reports. We organized our review by level of participation (ie, individuals, providers, and communities) and prevention (ie, primary, secondary, and tertiary). For individuals, several prevention strategies related to personal protection appear promising, but few have been appropriately evaluated. For providers of health care, five prevention measures are recommended, including such primary prevention activities as counseling and patient education in addition to the usual diagnosis and treatment. Specific evidence supporting the efficacy of these provider practices, however, is limited. For communities, maintaining comprehensive sexually transmitted disease control strategies to prevent lower genital tract chlamydial and gonococcal infection is most important in reducing both symptomatic and asymptomatic PID. We provide specific recommendations for preventing PID and outline research needs. PMID- 1942404 TI - Assessing risk for pelvic inflammatory disease and its sequelae. AB - To assess the risk for pelvic inflammatory disease (PID), a practitioner must evaluate the likelihood that a woman has PID or will be exposed to a sexually transmitted disease causing PID. Successful risk assessment depends on accurate information about variables influencing risk of PID. To determine the current state of knowledge about PID risk variables, we examined data in published reports. Data on each risk variable were scrutinized to discern which link(s) in the PID risk chain it affects (acquisition of a sexually transmitted disease, development of PID, or development of PID sequelae) and whether it is a risk marker or a risk factor. Most PID risk variables, particularly sexual behaviors, are associated with acquisition of a sexually transmitted disease, rather than development of PID itself. With the exception of age, demographic and social indicators of risk appear to be risk markers, while contraceptive practices appear more often to be risk factors than risk markers. Additional data are needed for most PID risk variables confidently to categorize them as risk factors. Enough information is available, however, to begin assessing risk for PID, so that appropriate counseling can ensue and timely diagnosis can be made. PMID- 1942406 TI - Pelvic inflammatory disease. PMID- 1942405 TI - Pathogenesis of pelvic inflammatory disease. What are the questions? AB - Pelvic inflammatory disease is usually caused by Chlamydia trachomatis or Neisseria gonorrhoeae. Chlamydiae and gonococci are primary pathogens of the cervix and often ascend. Resultant damage to the cervix may permit organisms to move upward, but this mechanism of action is not well understood. Puberty and hormones, particularly oral contraceptives, may enhance chlamydial infection, but the mechanisms and likelihood of spread to the upper tract are ill defined. Upper tract infection with C trachomatis involves an acute phase, characterized by an influx of polymorphonuclear leukocytes and a chronic or persistent phase characterized by the presence of mononuclear cells (delayed hypersensitivity). Gonococci invade nonciliated epithelial cells, but are toxic to ciliated cells, due to elaborated lipooligosaccharides and peptidoglycan. Certain gonococci stimulate chemotaxis of polymorphonuclear leukocytes whose release of toxic metabolites may damage tissue. The immunologic mechanisms that permit specific host responses to these two organisms are now being elucidated and should receive more attention by researchers. PMID- 1942407 TI - Portable heart pump recipient recovering well; evaluation begins of role for this technology. PMID- 1942408 TI - Treatment proposed for chronic fatigue syndrome; research continues to compile data on disorder. PMID- 1942409 TI - Delayed testing, tainted transfusions alleged. PMID- 1942410 TI - Pace of gene therapy picking up. PMID- 1942411 TI - From the Secretary of Health and Human Services. PMID- 1942412 TI - From the Health Care Financing Administration. PMID- 1942413 TI - From the Centers for Disease Control. Unavailability of streptomycin, para aminosalicylic acid--United States. PMID- 1942414 TI - A piece of my mind. Both sides of the story. PMID- 1942415 TI - Amyloid deposition in the eyelids. PMID- 1942416 TI - Cholesterol screening: hits and misses. PMID- 1942417 TI - Official misuse of tobacco industry propaganda: report of a Trojan horse. PMID- 1942418 TI - Where there's smoke there are liars. PMID- 1942419 TI - Bias estimates of mortality using MedisGroups. PMID- 1942420 TI - Recombinant erythropoietin and Medicare payment. PMID- 1942421 TI - Recombinant interferon gamma in condylomata acuminata. PMID- 1942422 TI - Effects of zidovudine therapy in minority and other subpopulations with early HIV infection. AB - OBJECTIVE--The purpose of this study was to determine whether the beneficial effects of zidovudine seen overall in two recently completed placebo-controlled clinical trials are also apparent in blacks, Hispanics, women, and intravenous drug users. DESIGN--Two double-blind placebo-controlled randomized clinical trials, protocols 016 and 019, conducted by the AIDS Clinical Trials Group. SETTING--University-based referral centers. PARTICIPANTS--Two thousand forty eight persons with asymptomatic or mildly symptomatic human immunodeficiency virus infection were analyzed. Of these, 155 were black, 190 were Hispanic, 144 were women, and 221 were intravenous drug users. All randomized subjects were included in the analysis. INTERVENTION--Participants in the AIDS Clinical Trials Group protocol 016 were assigned to receive a placebo or a 1200-mg daily dose of zidovudine. Participants in the AIDS Clinical Trials Group protocol 019 were assigned to receive a placebo, a 500-mg daily dose of zidovudine, or a 1500-mg daily dose of zidovudine. MAIN OUTCOME MEASURE--Progression to AIDS. RESULTS--The rates of progression to AIDS in subjects receiving zidovudine were significantly lower than those in subjects receiving a placebo among blacks (P = .03), whites (relative risk [RR] = 2.3, 95% confidence interval [CI] = 1.5 to 3.6, P less than .0001), Hispanics (RR = 4.4, CI = 1.2 to 16.8, P = .02), non-Hispanics (RR = 2.3, CI = 1.5 to 3.6, P = .0002), men (RR = 2.5, CI = 1.6 to 3.8, P less than .0001), and non-intravenous drug users (RR = 2.5, CI = 1.6 to 4.0, P less than .0001). The rates of disease progression for subjects receiving zidovudine were not statistically different from those receiving placebo for women (RR = 3.3, CI = 0.3 to 36.3, P = .31) or for intravenous drug users (RR = 2.0, CI = 0.7 to 6.2, P = .21); however, in both instances the estimated RRs were similar to those for men and non-intravenous drug users. CONCLUSIONS: -Although the two studies used for this analysis were not specifically designed to assess the effects of zidovudine in each separate subpopulation, the data suggest that the beneficial effects of zidovudine reported for the entire study population also apply to the subpopulations of blacks, Hispanics, women, and intravenous drug users. PMID- 1942424 TI - HMO market penetration and hospital cost inflation in California. AB - OBJECTIVE--Health maintenance organizations (HMOs) have stimulated price competition in California hospital markets since 1983, when the state legislature eliminated barriers to selective contracting by conventional health insurance plans. This study measures the impact of HMO-induced price competition on the rate of inflation in average cost per admission for 298 private, non-HMO hospitals between 1982 and 1988. DATA--HMO market penetration was calculated using discharge abstract data on insurance coverage, ZIP code of residence, and hospital of choice for 3.35 million patients in 1983 and 3.41 million patients in 1988. Data on hospital characteristics were obtained from the American Hospital Association and other sources. RESULTS: -HMO coverage grew from an average of 8.3% of all admissions in local hospital markets in 1983 to 17.0% of all admissions in 1988. The average rate of growth in costs per admission between 1982 and 1988 was 9.4% lower in markets with relatively high HMO penetration compared with markets with relatively low HMO penetration (95% confidence interval, 5.2 to 13.8). Cost savings for these 298 hospitals are estimated at $1.04 billion for 1988. CONCLUSION--Price competition between HMOs and conventional health insurers can significantly reduce hospital cost inflation if legislative barriers to selective contracting are removed. The impact of competition in California was modest, however, when evaluated in terms of the 74.5% average rate of California hospital cost inflation during these years. PMID- 1942423 TI - Racial and ethnic differences in outcome in zidovudine-treated patients with advanced HIV disease. Zidovudine Epidemiology Study Group. AB - OBJECTIVES--To determine if racial-ethnic differences exist in survival, disease progression, and development of myelosuppression in zidovudine-treated patients with advanced human immunodeficiency virus (HIV) disease. DESIGN--Prospective observational study. SETTING: -Hospital and private clinics in 12 metropolitan centers. PATIENTS: -The study included 754 non-Hispanic white, 165 black, and 106 Hispanic patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex (ARC) who received up to 2 years of zidovudine therapy. OUTCOME MEASURES--Survival, development of Pneumocystis carinii pneumonia (PCP), other opportunistic infections, and myelosuppression. RESULTS--At initiation of zidovudine therapy, Hispanic and particularly black patients had more advanced HIV disease than white patients, as indicated by lower baseline CD4+ counts, hematocrits, and AIDS-defining diagnoses. Black patients with AIDS also had a worse prognosis compared with white and Hispanic patients with AIDS. The product limit survival rates at 2 years for white, black, and Hispanic patients with AIDS were 40%, 27%, and 39%, respectively (black vs white, P = .01; Hispanic vs white, P = .32, by the log-rank test). The respective proportions of patients who developed PCP at 2 years were 46%, 66%, and 44% (black vs white, P = .0001; Hispanic vs white, P = .86) and for other opportunistic infections the proportions were 56%, 63%, and 63%, respectively (black vs white, P = .03; Hispanic vs white, P = .09). There were no significant racial-ethnic differences in survival or in the development of opportunistic infections for patients with ARC, and there were no differences in the incidence of myelosuppression or dose reduction or suspension for patients with either ARC or AIDS. After adjusting for more advanced HIV disease (mainly low CD4+ counts and hematocrits), black race was no longer a significant independent predictor of survival. Adjustment for racial differences in the use of PCP prophylaxis accounted for most of the excess risk for the development of PCP in black patients compared with white patients with AIDS. CONCLUSIONS--Racial differences in survival and the development of opportunistic infections are mainly due to the more advanced HIV disease in black patients when zidovudine therapy is started and to their less frequent use of PCP prophylaxis. Innovative approaches are needed to ensure more widespread use of and earlier access to zidovudine therapy and PCP prophylaxis. PMID- 1942425 TI - The susceptibility of young adult Americans to vaccine-preventable infections. A national serosurvey of US Army recruits. AB - OBJECTIVE: Due to recent resurgences of measles, mumps, and rubella among young US adults, we sought to generate antibody prevalence data for national and military immunization policy evaluations. DESIGN: We used a questionnaire and serological survey of Army recruits to assess antibody status to measles, mumps, rubella, and varicella by enzyme-linked immunosorbent assay and to poliovirus types 1, 2, and 3 by microneutralization assay. SETTING: Basic training reception centers at Fort Benning, Ga., and Fort Jackson, SC. PATIENTS: The study included 1547 US Army recruits who were inducted during September and October 1989. OUTCOME MEASURES: Seronegativity by various demographic factors. RESULTS: Seronegativity rates, directly adjusted to the 15- to 24-year-old US population in 1980, were 20.7% for measles, 15.6% for mumps, 17.5% for rubella, and 6.9% for varicella. For measles, mumps, and rubella, susceptibility was less in females, blacks, and college-educated recruits, and varicella susceptibility was greater in females and blacks. Recruitment who were born after 1969 lacked measles, mumps, and rubella antibodies more often than older recruits. The adjusted seronegativity rates for poliovirus types 1, 2, and 3 were 2.3%, 0.6%, and 14.6%, respectively; trends by age, sex, and race-ethnicity were generally unremarkable. CONCLUSIONS: Among young adult Americans, susceptibility to measles, mumps, and rubella is unevenly distributed and may be substantial. Our findings support national objectives to further improve immunization coverage in school-age and adult populations and provide further impetus for legislation requiring college entrants to present evidence of having received at least two doses of measles vaccine, with one on or after entry into elementary school. PMID- 1942426 TI - Astemizole-induced cardiac conduction disturbances in a child. AB - The newly available antihistamine astemizole (Hismanal) has been previously associated with hemodynamically significant cardiac tachydysrhythmias. We describe a 3-year-old girl who developed multiple different cardiac dysrhythmias after an astemizole overdose. No hemodynamic compromise occurred, and the electrocardiogram returned to normal without use of antiarrhythmic agents within 7 hours. PMID- 1942427 TI - Sexual misconduct in the practice of medicine. Council on Ethical and Judicial Affairs, American Medical Association. AB - The American Medical Association's Council on Ethical and Judicial Affairs recently reviewed the ethical implications of sexual or romantic relationships between physicians and patients. The Council has concluded that (1) sexual contact or a romantic relationship concurrent with the physician-patient relationship is unethical; (2) sexual contact or a romantic relationship with a former patient may be unethical under certain circumstances; (3) education on the ethical issues involved in sexual misconduct should be included throughout all levels of medical training; and (4) in the case of sexual misconduct, reporting offending colleagues is especially important. PMID- 1942428 TI - Medical apartheid. An American perspective. AB - The suppressive policies and practices of apartheid in South Africa have directly contributed to preventable morbidity and mortality in black Africans. Due to socioeconomic segregation ("functional apartheid"), America's citizens of color also suffer excess death and disability. Health status measurements in the United States confirm the failure of the current fragmented health care system to recognize or respond to the unmet need or the barriers that exist. Predictably, the changes needed to improve the health status of black South Africans are similar to those that are necessary to remedy the situation in the United States. Community-Oriented Primary Care is a health service provision model that holds promise as a comprehensive community-based strategy that can begin to address some of the shortcomings of the current medical care systems of both nations. PMID- 1942429 TI - Zidovudine. Does it work for everyone? PMID- 1942430 TI - Market forces and health care costs. PMID- 1942431 TI - Cooling the burn from hot peppers. PMID- 1942432 TI - Side effects of raw honey. PMID- 1942433 TI - Global full-court press against HIV, AIDS spurred by player's infection. PMID- 1942434 TI - Medical schools receive a message: reform yourselves, then take on health care system. PMID- 1942435 TI - Proposed card, intended to facilitate medical billing, record keeping, draws mixed reviews. PMID- 1942436 TI - From the Congressional Office of Technology Assessment. PMID- 1942437 TI - From the Health Care Financing Administration. PMID- 1942438 TI - From the Centers for Disease Control. Body-weight perceptions and selected weight management goals and practices of high school students--United States, 1990. PMID- 1942439 TI - From the Centers for Disease Control. Sensitivity of death certificate data for monitoring diabetes mortality--Diabetic Eye Disease Follow-Up Study, 1985-1990. PMID- 1942440 TI - A piece of my mind. The history of Crete. PMID- 1942442 TI - Of mugs and marketing. PMID- 1942441 TI - Prevention of stroke in older persons with isolated systolic hypertension. PMID- 1942443 TI - Emergency treatment of acute drug ingestions. PMID- 1942444 TI - Coated plaquenil tablets: potential risk for children? PMID- 1942445 TI - Access to care. PMID- 1942446 TI - The eternal battle of sex vs gender. PMID- 1942447 TI - Touching on the keys to visual memory. PMID- 1942448 TI - Malpractice suit emotional trauma. PMID- 1942449 TI - Thromboembolism in AIDS-related Kaposi's sarcoma. PMID- 1942450 TI - Primary care physicians and AIDS. Attitudinal and structural barriers to care. AB - OBJECTIVE: To explore the extent to which primary care physicians are providing health care for people with human immunodeficiency virus (HIV) infection and to document barriers to HIV care giving. DESIGN: National random-sample mailed survey. PARTICIPANTS: Population-based random sample of 2004 US general internists, family physicians, and general practitioners in 1990. Response rate was 59%. MAIN OUTCOME MEASURES: HIV treatment experience, willingness to treat HIV-infected patients, negative attitudes toward homosexuals and intravenous drug users, fear of contagion of the acquired immunodeficiency syndrome (AIDS), perceived lack of information about AIDS, and time demands of HIV care. RESULTS: Most physicians (75%) had treated one or more patients with HIV infection. A majority (68%) believed that they had a responsibility to treat people with HIV infection, yet half (50%) indicated that they would not, if given a choice. Over 80% of respondents believed that they lacked information about AIDS and that caring for people with AIDS is time consuming. Further, 35% of respondents agreed that they "would feel nervous among a group of homosexuals" and 55% expressed discomfort about having intravenous drug users in their practice. Physicians who had treated 10 or more HIV-infected patients expressed less negativity toward members of these stigmatized groups who are likely to be HIV infected. CONCLUSIONS: These data suggest that many primary care physicians are responding professionally to the AIDS epidemic but that attitudinal barriers may be hindering some physicians from providing treatment to HIV-infected patients. PMID- 1942451 TI - House staff recruitment to municipal and voluntary New York City residency programs during the AIDS epidemic. AB - OBJECTIVE: To determine the impact on house staff recruitment of large numbers of patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Trends in yearly survey data from the National Resident Matching Program from 1983 to 1990 were examined for residency programs in New York City, NY, where AIDS is epidemic, in the four largest US cities with the fewest AIDS cases, and nationally. Within New York City, trends were compared for residency programs serving large numbers of AIDS patients (high AIDS) and for other programs (low AIDS). MAIN OUTCOME MEASURES: Number of matches in each study year as compared with the baseline year of 1983 and the yearly percentage of positions offered that were filled by matches. RESULTS: During the study period, New York City experienced a greater decline in US graduate matches than did the four low-AIDS cities or the nation. Within New York City, recruitment to municipal programs, all with large AIDS patient populations, dropped from 241 to 173 matches (28.2%) despite a 3.6% increase in positions. However, recruitment to both high-AIDS and low-AIDS voluntary programs improved in all years except 1990. After controlling for numbers of offered positions, high-AIDS and low-AIDS voluntary programs again showed similar trends until 1990. CONCLUSIONS: These observations cannot be attributed to AIDS alone. Multiple economic and social factors, including AIDS, may have contributed. PMID- 1942452 TI - Computerized surveillance of adverse drug events in hospital patients. AB - OBJECTIVE: To develop a new method to improve the detection and characterization of adverse drug events (ADEs) in hospital patients. DESIGN: Prospective study of all patients admitted to our hospital over an 18-month period. SETTING: LDS Hospital, Salt Lake City, Utah, a 520-bed tertiary care center affiliated with the University of Utah School of Medicine, Salt Lake City. PATIENTS: We developed a computerized ADE monitor, and computer programs were written using an integrated hospital information system to allow for multiple source detection of potential ADEs occurring in hospital patients. Signals of potential ADEs, both voluntary and automated, included sudden medication stop orders, antidote ordering, and certain abnormal laboratory values. Each day, a list of all potential ADEs from these sources was generated, and a pharmacist reviewed the medical records of all patients with possible ADEs for accuracy and causality. Verified ADEs were characterized as mild, moderate, or severe and as type A (dose dependent or predictable) or type B (idiosyncratic or allergic) reactions, and causality was further measured using a standardized scoring method. OUTCOME MEASURE: The number and characterization of ADEs detected. RESULTS: Over 18 months, we monitored 36,653 hospitalized patients. There were 731 verified ADEs identified in 648 patients, 701 ADEs were characterized as moderate or severe, and 664 were classified as type A reactions. During this same period, only nine ADEs were identified using traditional detection methods. Physicians, pharmacists, and nurses voluntarily reported 92 of the 731 ADEs detected using this automated system. The other 631 ADEs were detected from automated signals, the most common of which were diphenhydramine hydrochloride and naloxone hydrochloride use, high serum drug levels, leukopenia, and the use of phytonadione and antidiarrheals. The most common symptoms and signs were pruritus, nausea and/or vomiting, rash, and confusion-lethargy. The most common drug classes involved were analgesics, anti-infectives, and cardiovascular agents. CONCLUSION: We believe that screening for ADEs with a computerized hospital information system offers a potential method for improving the detection and characterization of these events in hospital patients. PMID- 1942453 TI - Can practice guidelines reduce the number and costs of malpractice claims? AB - Practice guidelines have the potential to reduce the number of malpractice cases and the costs of settling them. However, for practice guidelines to exert any influence, they must be assumed to be (1) developed for conditions or procedures that frequently lead to events for which negligence claims are filed; (2) widely accepted in the medical profession; (3) fully integrated into clinical practice; and (4) straightforward and readily interpreted in a litigation setting. Because the validity of each of these assumptions can be questioned, the idea that inserting practice guidelines into the existing litigation process will generate large savings in the near future is overly optimistic. PMID- 1942454 TI - HIV testing. State of the art. PMID- 1942455 TI - Concussion in sports. Guidelines for the prevention of catastrophic outcome. AB - Concussion (defined as a traumatically induced alteration in mental status, not necessarily with loss of consciousness) is a common form of sports-related injury too often dismissed as trivial by physicians, athletic trainers, coaches, sports reporters, and athletes themselves. While head injuries can occur in virtually any form of athletic activity, they occur most frequently in contact sports, such as football, boxing, and martial arts competition, or from high-velocity collisions or falls in basketball, soccer, and ice hockey. The pathophysiology of concussion is less well understood than that of severe head injury, and it has received less attention as a result. We describe a high school football player who died of diffuse brain swelling after repeated concussions without loss of consciousness. Guidelines have been developed to reduce the risk of such serious catastrophic outcomes after concussion in sports. PMID- 1942456 TI - Use of sedating drugs and neuromuscular blocking agents in patients requiring mechanical ventilation for respiratory failure. A national survey. AB - OBJECTIVE: To assess current use of sedating drugs and neuromuscular blocking agents in patients requiring mechanical ventilation at US hospitals that participate in the training of pulmonary fellows. DESIGN: Surveys were mailed in September 1990 to the head nurses of medical intensive care units at 265 US hospitals that were listed in an annual guide listing pulmonary fellowship training programs. In the survey, sedating drugs were defined as medications prescribed to treat anxiety, agitation, or sleeplessness. These included opiates, anesthetics, or neuroleptic agents when used for any of these purposes. SURVEY RESPONDENTS: Surveys were received from nurses at 164 hospitals (62% response rate) representing 93 medical schools and 100 pulmonary fellowship training programs. Nearly half of the respondents worked at university hospitals. Most worked as head nurses in medical (70%) or medical-surgical (21%) intensive care units (ICUs). RESULTS: Sedating drugs were given to patients undergoing mechanical ventilation at virtually all the ICUs surveyed, and 36% used these drugs routinely (greater than 70% of patients). Opiates and benzodiazepines were employed most commonly; haloperidol lactate was widely used as well. Intermittent intravenous injection was the preferred method of administration; 62% of the ICUs also gave these drugs by continuous intravenous infusion. Neuromuscular blocking agents were also used at nearly all the ICUs surveyed; however, most gave these drugs to fewer than 20% of patients experiencing respiratory failure. Orders for the use of sedating drugs and neuromuscular blocking agents were written exclusively by house staff at 65% of the ICUs surveyed. CONCLUSIONS: Sedating drugs and neuromuscular blocking agents are widely used for patients requiring mechanical ventilation in ICUs at US teaching hospitals. There is considerable variation in the choice, frequency, and method of administration. Given the expense (up to $1000 a day) and the potential hazards to patients of prolonged deep sedation and paralysis, more research is warranted to determine optimal use of these drugs during mechanical ventilation. PMID- 1942457 TI - The duty to "attend upon the sick'. PMID- 1942458 TI - Monitoring of adverse drug events in hospitals. PMID- 1942459 TI - From the Office of the General Counsel. Should practice parameters be the standard of care in malpractice litigation? PMID- 1942460 TI - MD-aided suicide voted down; both sides say debate to continue. PMID- 1942461 TI - Circulatory indirect calorimetry in the critically ill. AB - Circulatory indirect calorimetry (CIC) is a potentially useful method to assess the energy requirements of critically ill patients. Unlike respiratory indirect calorimetry (RIC), which measures oxygen utilization from inhaled and exhaled gases, CIC measures oxygen utilization from arterial and mixed venous blood. Twenty-two measurements in eight critically ill patients comparing RIC, CIC, and commonly used estimates of energy expenditure were performed. A significant correlation between RIC and CIC was identified (r = 0.831, p less than 0.001). Poor correlation was noted with either method and the commonly used estimates. CIC may be a useful tool in estimating energy expenditures in the critically ill. PMID- 1942462 TI - Risk factors for central venous catheter-related vascular erosions. AB - Risk factors for superior vena cava perforations following central venous catheterization for total parenteral nutrition were identified in a retrospective study of 1058 catheters in 853 patients; 540 of these catheters were size 16 gauge (51%) and 518 size 14-gauge (49%). Of the size 14-gauge catheters, 274 (53%) were right-sided and 244 (47%) were left-sided subclavian catheters. Four patients (0.4%) had superior vena cava perforation. All had left-sided large bore 14-gauge catheters. All patients experienced acute symptoms and all had pleural effusions. There was no mortality directly related to vascular erosions. Two risk factors were identified for this complication: (1) catheters originating from the left side (p less than 0.05), or (2) large catheters (size 14-gauge or larger) (p less than 0.01). We conclude that large bore or left-sided central venous catheter placement represents an increased risk of superior vena cava perforation. PMID- 1942463 TI - Action of enterally administered ornithine alpha-ketoglutarate on protein breakdown in skeletal muscle and liver of the burned rat. AB - Several studies concerning burn patients have shown that supplementation of enteral nutrition with ornithine alpha-ketoglutarate (OKG) favorably modifies protein metabolism. Therefore, the effect of OKG administration on muscular and hepatic protein catabolism was evaluated in burned rats. Four groups of six rats were used. Two groups were scalded by immersion of the dorsum in water at 90 degrees C for 10 seconds and then starved for 24 hours. Controlled enteral nutrition was then administered in three boluses daily (Osmolite, 210 kcal/kg/d, 1.2 g N/kg/d); one group was supplemented with OKG (5 g/kg/d, ie, 0.68 g N/kg/d), while the other group received an equivalent amount of nitrogen in the form of glycine. One group of healthy control rats received Osmolite supplemented with glycine and the last group was fed ad libitum. The animals were killed after 2 days of nutrition. Protein catabolism was assessed in vitro by measuring the amount of valine (liver catabolism) and phenylalanine (muscle catabolism) released into the incubation medium of isolated tissues. Tissular and serum glutamine were also assayed. Burn injury induced muscle hypercatabolism without affecting hepatic catabolism. The administration of OKG limited both muscle weight loss and muscle protein hypercatabolism and significantly improved the muscle glutamine pool. These results demonstrate the nitrogen-sparing effect of OKG in muscle in hypercatabolic states. PMID- 1942464 TI - Effect of glutamine infusions on glutamine concentration and protein synthetic rate in rat muscle. AB - Studies were undertaken in sedated and unsedated rats to raise the depleted intramuscular glutamine concentrations produced by aseptic abscesses, and to assess the effect of this change on muscle protein fractional synthetic rate. Age and weight-matched control animals were also included in the study. The rats were infused for up to 5 hours via the lateral tail vein with 1 mL/100 g of body weight per hour of either saline or 0.22 M glutamine. The intramuscular concentration of glutamine (mmol/L of intracellular water), which was reduced by 45% after turpentine in the sedated animals, was restored to within 79% of control values, but the muscle fractional protein synthetic rate, which was also reduced by 41% in these animals, was not improved by the glutamine infusions. Glutamine administration also failed to increase muscle protein synthesis in unsedated rats and in those supplemented with a liquid meal. It is concluded that acute elevations in muscle glutamine concentrations do not increase protein synthesis in this tissue and that therefore glutamine is unlikely to be a mediator in the control of muscle protein synthesis under these circumstances. PMID- 1942465 TI - Clenbuterol treatment increases muscle mass and protein content of tumor-bearing rats maintained on total parenteral nutrition. AB - Treatment of tumor-bearing (TB) and control rats with the anabolic beta-2 agonist drug clenbuterol (CLE) for 14 days reduced food intake for 4 days initially. Feeding was increased in anorectic TB rats, however, during the last 7 days of drug administration. Since minimal muscle savings were observed in chow-fed TB rats treated with CLE, the anabolic effects of this drug were investigated in a second experiment on TB rats maintained on total parenteral nutrition (TPN). Sixteen days after the subcutaneous transplantation of methylcholanthrene-induced sarcomas rats was begun on a 2-week schedule of TPN. One group of these rats was treated daily for 14 days with CLE, while the remaining rats received injections of saline. Additional groups of TB and nonTB rats were maintained on rat chow for this period and treated with saline. Although TB rats maintained on rat chow or TPN and treated with saline exhibited significantly decreased gastrocnemius muscle weight and protein content, treatment of TB-TPN rats with clenbuterol normalized muscle mass and increased muscle protein content significantly and increased plasma concentrations of branched-chain amino acids. These results indicate that although nutritional support of TB organisms does not result in protein repletion, the addition of an anabolic drug renders the nutritional support highly efficacious. PMID- 1942466 TI - In vitro assessment of vancomycin HCl compatibility after coinfusion with a specialized amino acid formulation. AB - Vancomycin usage at British Columbia's Children's Hospital has increased substantially in the Special Care Nursery as a consequence of a study demonstrating a reduced morbidity and mortality in neonates with necrotizing enterocolitis when treated with vancomycin and cefotaxime. The inability to place more than one peripheral intravenous access necessitates interruption of parenteral nutrition to infuse vancomycin, resulting in a reduction of the planned daily intake of these neonates. This is clinically significant with the administration of vancomycin because of the long administration period required for this drug (60 minutes). This study was designed to assess the physical and chemical stability of vancomycin with a standard neonatal parenteral nutrition solution, Vamin A, when coadministered through the same intravenous line. To simulate the actual clinical setting, the dose of vancomycin and the infusion rate of Vamin A were chosen to represent those commonly used in a 1-kg neonate. Physical compatibility was assessed using effluent obtained after coinfusion of vancomycin with parenteral nutrition solution. Duplicate samples were visually checked for color changes and precipitate. High-pressure liquid chromatography (HPLC) and pH testing were used to assess chemical compatibility of vancomycin. The results of physical compatibility revealed no color change or precipitate. No changes in pH were observed. HPLC determination confirmed that there were no significant time-dependent changes in vancomycin stability. The samples were studied over 24 hours to determine the rate of degradation of vancomycin, if any, under various temperature conditions. The concentrations were not significantly different from each other at the different temperatures studied. Thus, there was no apparent change in the concentration of vancomycin in the presence of Vamin A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942467 TI - Effect of methionine-deprived nutrition on cell growth and cell kinetics in cell cultures and experimental tumors. AB - The effect of methionine-deprived nutrition on cell growth and cell kinetics was investigated in cell cultures and in tumor-bearing rats using the total parenteral nutrition (TPN) technique. A simultaneous flow cytometric measurement of the cellular DNA content and the amount of 5-bromodeoxyuridine incorporated into cellular DNA was performed for analysis of cell kinetics. The methionine free medium demonstrated a cytocidal effect on the growth of SLC cells after 6 hours of culturing. It decreased viability from 80% in the control medium to 23%, and it decreased the S phase and increased the G0/G1 phase of the cell cycles. The methionine-deprived medium showed a concentration-dependent inhibition in cellular growth. Methionine-deprived TPN was seen to inhibit AH109A and SLC tumor growth compared with conventional TPN and decreased the S phase and increased the G0/G1 phase of cell cycles. These results confirm that methionine deprivation blocks cells from processing into the G1 phase and recycling, and that it is effective in inhibiting tumor growth in cultures and in vivo. PMID- 1942468 TI - Increased lipoprotein X causes hyperlipidemia during intravenous administration of 10% fat emulsion in man. AB - To clarify the mechanisms of hyperlipidemia during intravenous Intralipid 10%, lipoprotein profiles including lipoprotein X were studied in 13 patients receiving 2.0 g of fat per kilogram per day by Intralipid 10% over a period of 8 weeks. All patients were fed exclusively by total parenteral nutrition providing 1.1 g of amino acid and 30 kcal/kg per day. Intravenous administration of Intralipid 10% caused a marked increase of low-density lipoprotein (LDL), phospholipid, and cholesterol, especially free cholesterol, whereas triglyceride, very-low-density lipoprotein, and high-density lipoprotein remained within the normal range. Lipid composition of LDL approximated that of lipoprotein X progressively with the intravenous Intralipid 10%. Quantification of lipoprotein X revealed that its increase was proportionate with that of LDL and total lipid. From these findings, hyperlipidemia during intravenous Intralipid 10% is induced almost exclusively by the increased lipoprotein X. PMID- 1942469 TI - M-mode and two-dimensional echocardiography in the routine follow-up of central venous catheters in children receiving total parenteral nutrition. AB - A retrospective study in 38 children (1 day to 7 years) on total parenteral nutrition (TPN) (1 month-24 months) with a central venous catheter (CVC) evaluated the contribution of two-dimensional echocardiography (2D) and M-mode in the follow-up of CVC location and early diagnosis of related complications. Fifty examinations were performed routinely in 21 patients (group I) and 40 in 17 patients for sepsis of the CVC or clinical suspicion of thrombosis (group II). The tip of the CVC was located in the upper right atrium in 17 cases (45%), superior vena cava in 14 cases (37%), jugular or subclavian vein in 5 cases (13%), and was not visualized in 2 cases (15%). In group I, 2D was normal in 19 cases, and catheter thrombosis suspected in 2 was not confirmed by digital angiography (DA). In group II, 2D was normal in 11 cases. In 6 patients, subxiphoid and suprasternal planes identified superior vena cava thrombus in the right atrium (DA confirmed the diagnosis in 2). In 2 pulmonary embolism occurred (1 case died); the remaining patients were successfully treated by medical therapy and removal of the catheter. Echocardiography is a useful noninvasive technique to control CVC tip location and follow-up. In this study, the sensitivity of cardiac thrombus detection by echocardiography was 100% and the specificity 93%; this method appeared, therefore, appropriate for early detection of cardiac thrombosis in pediatric patients on TPN. PMID- 1942470 TI - Selenium supplementation in low-birthweight premature infants: relationship to trace metals and antioxidant enzymes. AB - We attempted to study the effect of selenium supplementation upon trace metal metabolism in low-birthweight infants less than 1000 g birthweight. Serum levels of the trace metals copper, zinc, and selenium; and white blood cell glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were measured in conjunction with the trace metals when parenteral nutrition (TPN) was begun (sample A), at the initiation of enteral nutrition (sample B), and when TPN was discontinued (sample C). Two randomly selected groups of infants were evaluated: group S received selenium supplementation (1.34 micrograms/kg per d) in their parenteral nutrition solutions; group C was a control which did not receive selenium supplementation. Selenium levels declined to equally low levels in both groups by sample C, but were significantly higher in group S at sample B. GSH-Px activities demonstrated a significant increase at sample B in group S and then tended to decrease. In group C, GSH-Px tended to increase, then decreased significantly by sample C. Both groups received 20 micrograms/kg per d of copper in TPN, however, serum copper declined significantly at sample B in group S whereas there were no significant changes in group C. There were no significant changes in zinc and SOD levels. There were no significant differences between groups in clinical characteristics or outcome. This study suggests that a dose of supplemental selenium of 1.34 micrograms/kg per d in TPN is inadequate for low birthweight premature infants. Selenium supplementation may also affect copper metabolism. PMID- 1942471 TI - Total parenteral nutrition energy composition affects small intestinal disaccharidase activity in the newborn miniature pig. AB - Total parenteral nutrition (TPN) decreases disaccharidase activity in the small intestine of humans and miniature piglets. The possibility, however, that specific components of TPN (eg, the energy mix) will increase disaccharidase activity has largely been unexplored. The identification of such components would be particularly useful in the treatment of premature infants with immature gastrointestinal tracts and patients with small intestinal mucosal disease associated with decreased disaccharidase activity. To determine whether the TPN energy composition affects small intestinal disaccharidase activity, 7-day-old miniature piglet littermates were randomized to receive TPN containing either glucose (group G) or glucose and fat (group G/F) as the nonnitrogen energy source(s). The TPN regimens were isonitrogenous and isoenergetic. The piglets were not allowed oral intake during the 7 days they were maintained on TPN. At 14 days of age the piglets were killed and the small intestines analyzed for weight, protein, DNA, and disaccharidase activity. Body weight was similar between groups at both the beginning and end of the study. The TPN regimen did not affect small intestinal weight of protein and DNA content. However, jejunal and ileal sucrase and ileal maltase activities (mumol/min.kg body wt +/- SD) were greater in group G than those in group G/F (28 +/- 9 vs 19 +/- 11, p = 0.04; 13 +/- 7 vs 7 +/- 4, p = 0.037; and 31 +/- 8 vs 19 +/- 10, p = 0.0088, respectively). No differences in lactase activity were noted between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942472 TI - Effect of a lactase preparation on lactose content and osmolality of preterm and term infant formulas. AB - Lactose intolerance due to lactase deficiency often follows acute gastroenteritis. In such situations, a lactose-free formula may be indicated for preterm infants. Therefore, the effect of addition of lactase on the lactose content and osmolality of preterm and term infant formulas was studied. Lactose content of formulas at room temperature was decreased by approximately 50% 1 hour after addition of lactase. Concentration of lactose was reduced by 70% or more after 2 hours in all formulas. Because of the higher initial lactose concentration in term formulas, it took 24 hours to reach the same absolute lactose concentration (10 g/kg formula) found in preterm formulas after 2 hours. There was a moderate increase in osmolality in preterm formulas. The increase was greater in term formulas because of the greater initial concentration of lactose. The addition of lactase appears to be a suitable method for reduction of lactose content of preterm and term formulas, although the increase in osmolality of term formulas may preclude their clinical use. PMID- 1942473 TI - The relationship between enteral formula contamination and length of enteral delivery set usage. AB - Twenty-one delivery sets were collected from 21 patients who had received continuous Osmolite feedings over 24 hours. Delivery sets were than taken to the laboratory and hung for an additional 48 hours. In the laboratory, the delivery sets were rinsed with tap water and Osmolite was added every 12 hours. Formula samples were obtained from the delivery sets after they had been used for 24 hours, and every 12 hours during the additional 48 hours in the laboratory. Formula contamination was assessed by determining bacterial counts. Unacceptable contamination was defined as bacterial counts greater than or equal to 10(5) cfu/mL. The mean bacterial count was 2.8 x 10(5) cfu/mL at 24 hours, and all subsequent mean counts increased over time. There were statistically significant differences among the mean log bacterial counts at all time periods (p less than or equal to 0.0005) except between 36 hours and 48 hours (p = 0.019). Of the 21 delivery sets, 23.8% were unacceptably contaminated at 24 hours, and by 48 hours, 42.9% were unacceptable. These findings suggest that if 10(5) cfu/mL is used as a criterion, delivery sets should not be used for more than 24 hours in a hospital, and 24-hour use of delivery sets may even be too long. PMID- 1942474 TI - Lipiduria after intralipid infusion of a lipid emulsion in a boy with an abdominal trauma. AB - A 4-year-old boy with an abdominal trauma had lipiduria following treatment with total intravenous nutrition for 4 days. Renal function was normal throughout the course and the lipiduria ceased after withdrawal of the intravenous nutrition. The lipids were possibly excreted through the kidneys or entered the urine through a traumatic communication between the lymphatic vessels and the urinary system. Control of renal function and lipiduria after 1 year revealed normal conditions. PMID- 1942475 TI - Spontaneous migration of long-term indwelling venous catheters. AB - Our institution recently encountered two patients with an unusual complication of indwelling catheters, spontaneous migration of the catheter tip. Both patients had indwelling subcutaneous ports placed via the left subclavian vein into the superior vena cava for the treatment of breast cancer. Both catheters functioned well but were noted on follow-up radiographs to have repositioned themselves, one into the azygous vein and the other into the internal jugular vein. One patient required surgical intervention to properly position the catheter for further chemotherapy. Chest roentgenograms are indicated to confirm the continued appropriate position of indwelling catheters when their position is in doubt to minimize the likelihood of complications associated with delivery of caustic chemotherapeutic agents in low flow vessels. PMID- 1942477 TI - Pre-eclampsia. PMID- 1942476 TI - Pneumonia and continuous enteral feeding. PMID- 1942478 TI - Serum calcium, urea and uric acid levels in pre-eclampsia. AB - Serum calcium, urea and uric acid levels were determined in 100 normal pregnant women and 50 patients with pre-eclampsia. Serum calcium levels were significantly lower and urea and uric acid levels higher in pre-eclampsia. Low levels of calcium were found as early as 28 weeks and can therefore be used for early diagnosis of pre-eclampsia. PMID- 1942479 TI - Field trial of Saussurea lappa roots against nematodes and Nigella sativa seeds against cestodes in children. AB - Antinematodal efficacy of Saussurea lappa roots (Qust-e-Shereen) and anticestodal effect of Nigella sativa seeds (Kalonji) was studied in children infected naturally with the respective worms. The activities were judged on the basis of percentage reductions in the faecal eggs per gram (EPG) counts. The 50 mg/kg single dose of S. lappa and equivalent amount of its methanolic extract produced on days 7 and 15 percentage EPG reduction similar to 10 mg/kg of pyrantel pamoate. Similarly, single oral administration of 40 mg/kg of N. sativa, equivalent amount of its ethanolic extract and 50 mg/kg of niclosamide reduced the percentage of EPG counts not significantly different from each other on the days 7 and 15. Therefore, it is conceivable that these indigenous medicinal plants contain active principles effective against nematodes and cestodes. The crude drugs did not produce any adverse side effects in the doses tested. PMID- 1942480 TI - Occupational injuries and perception of hazards among road-side welding workers. AB - A cross-sectional survey was conducted to understand the extent of occupational injuries and the perception of hazards among the road-side welders in the city of Karachi. Burns and foreign body in eyes were reported to be the most common injuries. Few workers perceived their occupation as hazardous. Consequently, few of them reported using protective measures. A 3-step strategy was recommended to improve occupational safety for this and other related groups of workers. PMID- 1942481 TI - A 5 year retrospective case study of penetrating ocular trauma at the Aga Khan University Hospital, Karachi. AB - Ocular Trauma is an important cause of monocular visual impairment and blindness in younger age groups. We examined the cases of hospitalized ocular trauma from 1st January, 1985 through 30th July, 1990 using hospital medical records. The study comprised 27 patients (28 eyes), 51.8% of whom were under 16. The male female ratio was 2.8:1. Right eye was more commonly involved (66.6%) and one patient had bilateral ruptured globes. Children at play were most vulnerable (33.3%) followed by road accidents which was the major cause (29.6%) in adults. Sixteen (64.0%) eyes suffered some complications and their mean duration of presentation after injury was 28.4 hours. Traumatic cataract was the most common complication (50.0%) in this group, followed by vitreous haemorrhage (37.5%). Nine (36%) ocular injuries did not develop any complications and presented 14 hours (average) after injury. Most of the patients retained their vision on follow-up examination, but 16.0% lost their vision completely. Another 3 eyes had to be enucleated due to severe trauma and loss of vision. PMID- 1942482 TI - Visceral leishmaniasis in a six month old child: is congenital transmission of disease possible? PMID- 1942483 TI - Hepatic dysfunction in falciparum malaria. PMID- 1942484 TI - Fetal ascites as a cause of dystocia in labour. PMID- 1942485 TI - Osteonecrosis of femoral head in SLE patient after short period of corticosteroid therapy--a case report. PMID- 1942486 TI - Current concepts in the diagnosis and management of childhood asthma. PMID- 1942487 TI - Molecular nature of T-cell receptors. PMID- 1942488 TI - Laboratory techniques for examination of intestinal parasites. PMID- 1942489 TI - A new laboratory technique for malaria diagnosis. PMID- 1942490 TI - Electrocardiographically and symptomatically silent myocardial ischemia during exercise testing. AB - Certain patients with coronary artery disease (CAD) may have neither ST depression nor chest pain during exercise despite the presence of myocardial ischemia. The frequency and characteristics of such electrocardiographically and symptomatically silent ischemia were studied in 171 patients with both angiographically documented CAD and scintigraphically documented ischemia. Fifty six (33%) of 171 patients had neither ST depression nor chest pain (Group N), and 115 (67%) had ST depression and/or chest pain (Group P). The two groups were similar with respect to age, gender, the prevalence of prior infarction, and peak systolic blood pressure. Group N patients, however, had a higher mean peak heart rate and rate-pressure product, less severe scintigraphic ischemia, a lower lung thallium-201 uptake, and a smaller number of diseased vessels. Stepwise discriminant analysis showed a history of effort angina, lung thallium-201 uptake, and scintigraphic severity of ischemia to be significant discriminators between Groups N and P. In conclusion, electrocardiographically and symptomatically silent ischemia may be common during exercise in patients with CAD, and less severe ischemia may be one of important determinants. PMID- 1942492 TI - Role of the kinin-kallikrein system in the vasodilator action of an angiotensin converting enzyme inhibitor (captopril) on the systemic resistance and capacitance vessels of dogs. AB - We investigated the vasodilator effects of captopril (CAP) on the systemic capacitance and resistance vessels by measuring changes in the mean circulatory pressure (MCP) and total peripheral resistance (TPR) that occurred in response to the intravenous injection of CAP (1 mg/kg) in open-chest dogs. The following five groups of dogs received CAP: (1) Group of untreated dogs, (2) TSA Group in which the dogs were subjected to total spinal anesthesia (TSA), (3) Ang II Group in which the dogs received a continuous intravenous infusion of angiotensin II (Ang II), (4) APR + Ang II Group in which the dogs received a continuous intravenous infusion of Ang II after pretreatment with aprotinin (APR, 25,000 K.I.E.), a kallikrein inhibitor, and (5) IND + APR + Ang II Group in which the dogs received a continuous intravenous infusion of Ang II after pretreatment with indomethacin (IND, 5 mg/kg), a prostaglandin synthesis inhibitor, and APR. 1) CAP significantly decreased TPR and MCP in the untreated Group. 2) CAP significantly decreased TPR and MCP in the TSA Group. There were no significant differences in percentage change of TPR (% delta TPR) and percentage change of MCP (% delta MCP) between the untreated and TSA Groups. 3) In the Ang II Group, CAP decreased the elevated TPR significantly, but hardly affected the elevated MCP. 4) CAP significantly decreased TPR without significant change in MCP in the APR + Ang II Group. The % delta TPR was significantly smaller in this Group than in the Ang II Group. 5) CAP significantly decreased TPR without significant change in MCP in the IND + APR + Ang II Group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942491 TI - Effects of amiloride and an analogue on ventricular arrhythmias, contracture and cellular injury during reperfusion in isolated and perfused guinea pig heart. AB - The present study was designed to examine whether activation of Na+/H+ exchange and subsequent massive Ca2+ influx via Na+/Ca2+ exchange are involved in the pathogenesis of myocardial reperfusion injury. We tested the effects of 1 mM amiloride, which is known to inhibit both Na+/H+ and Na+/Ca2+ exchange, and 3 microM 5-(N-ethyl-N-isopropyl) amiloride (EIPA), which is known to act as a specific inhibitor against Na+/H+ exchange, on the incidence of ventricular arrhythmias, isovolumic left ventricular function and creatine kinase (CK) release during reperfusion after 15 or 30 min of global ischemia in the isolated and perfused guinea pig heart. Treatment of a normally perfused heart with amiloride decreased heart rate significantly and tended to increase coronary flow and left ventricular developed pressure (LVDP), whereas treatment with EIPA decreased all of these 3 measurements significantly. Treatment with amiloride or EIPA for 15 min before ischemia, and during reperfusion after 15 min of ischemia, under electrical pacing at 240 rpm to eliminate a negative chronotropic effect abolished ventricular tachycardia (VT) and ventricular fibrillation (VF) during reperfusion associated with highly significant inhibition of increases in left ventricular end-diastolic pressure (LVEDP) and CK release. Amiloride or EIPA pretreatment also inhibited the incidence of VF and increases in LVEDP and CK release significantly during reperfusion after 30 min of ischemia. However, amiloride was more effective in preventing these events than EIPA. The treatment with amiloride or EIPA only during reperfusion after 15 or 30 min of ischemia also decreased the incidence of VF and inhibited the increases in LVEDP and CK release significantly, though less effectively than the pretreatment modality. These results suggest that EIPA prevents ventricular arrhythmias, contracture and myocardial cellular injury during reperfusion after 15 min of ischemia by inhibiting Na+/H+ exchange, while amiloride exerts more powerful protection against these events than EIPA during reperfusion after 30 min of ischemia by inhibiting both Na+/H+ and Na+/Ca2+ exchange. PMID- 1942493 TI - Pathophysiology and pathogenesis of contractile failure in stunned myocardium. AB - To investigate excitation-contraction coupling in stunned myocardium, intracellular free calcium concentration [( Ca2+]i) was measured before and after ischemia in perfused hearts using gated 19F NMR and the Ca2+ indicator 5F-BAPTA. Maximal Ca(2+)-activated force was also measured in parallel experiments. Stunned myocardium was created by reperfusion after 15 min global ischemia at 37 degrees C in isolated ferret hearts. In stunned myocardium, peak [Ca2+]i was paradoxically higher than that in control, but maximal Ca(2+)-activated pressure was lower in stunned hearts. These results indicate that contractile failure in stunned myocardium is due to a decrease in the myofilament sensitivity to Ca2+ as well as to a decrease in maximal Ca(2+)-activated force; failure of activator Ca2+ delivery cannot be implicated. The role of intracellular calcium overload in the pathogenesis of stunned myocardium was also investigated. Time-averaged 19F NMR measurements directly revealed the increase in [Ca2+]i during ischemia and in the early phase of reperfusion. The strategies to prevent Ca overload during reperfusion with modified reperfusate succeeded in preserving contractile function. Transient Ca overload without ischemia induced by different causes, i.e., high [Ca]0 perfusion, ventricular fibrillation or treatment with adriamycin, also produced contractile dysfunction that outlasted the interventions themselves. Thus, we propose that transient Ca overload during ischemia and early reperfusion initiates long-lasting contractile dysfunction in stunned myocardium. PMID- 1942494 TI - Effects of cardiac sympathetic nervous system on the stunned myocardium experimental study with 123I-metaiodobenzylguanidine. AB - 123I-Metaiodobenzylguanidine (123I-MIBG) uptake in the stunned myocardium was investigated in open chest dogs. 123I-MIBG is a tracer taken up in presynaptic adrenergic vesicles and reflects the function of the myocardial sympathetic nervous system. This study revealed that in the stunned myocardium without infarct, 123I-MIBG uptake was normal up to 40 minutes of ischemia and that exogenous noradrenaline improved deteriorated regional wall motion with increased uptake of 123I-MIBG. However, uptake of 123I-MIBG per flow decreased with infarct in ischemic areas, and it showed a linear relation with regional wall motion. Thus, in the absence of infarction 123I-MIBG is a tracer to differentiate stunning from more severe ischemia with persistent wall motion abnormality. Normal uptake and storage of 123I-MIBG in the stunned condition suggests that catecholamine release or second effector mechanism may relate to the mechanism. PMID- 1942495 TI - Ventricular wall motion and NE release in post-ischemic reperfused myocardium. AB - To clarify the relationship between post-ischemic myocardial dysfunction and local cardiac sympathetic nerve function, we measured regional myocardial length and norepinephrine (NE) release during sympathetic nerve stimulation in 32 mongrel dogs. Coronary occlusion was produced by balloon occluder for 15 min and reperfused for 60 min. Dogs were divided into 3 groups as follows; Group 1 (n = 14): Sympathetic nerve stimulation, Group 2 (n = 9): Pre-treatment with yohimbine hydrochloride (0.2 mg/kg) and sympathetic nerve stimulation, Group 3 (n = 9): Exogenous NE administration. Sympathetic nerve stimulation or NE infusion were performed before occlusion and after reperfusion. In group 1, the extent of the increase in systolic shortening during sympathetic nerve stimulation (delta - shortening) lowered at 5 min after reperfusion and augmented progressively. But, delta-shortening at an early reperfusion period did not reduce in group 2 and 3. NE release from the ischemic myocardium decreased in group 1 and did not recover for 60 min. When the cardiac sympathetic nerve was denervated with 90% phenol solution, NE release further decreased in group 1. On the other hand, NE release did not decrease in group 2. These results indicate that the response to sympathetic nerve stimulation decreased in post-ischemic reperfused myocardium and this was due to diminished NE release. It was considered that sympathetic nerve conduction was not completely impaired in post-ischemic myocardium and pre synaptic alpha-2 receptor mediated negative feedback mechanism would play an important role in these diminished NE release. PMID- 1942496 TI - Radionuclide assessment of stunned myocardium by alterations in perfusion, metabolism and function. AB - A method for the diagnosis of stunned myocardium has not yet been established, although it has been retrospectively demonstrated in patients after intracoronary thrombolysis, unstable angina, and coronary revascularization. In this study, radionuclide cardiac imaging was carried out to evaluate the existence of stunned myocardium. 1) Gated blood pool scanning was performed in patients undergoing intracoronary thrombolysis both at the time of reperfusion (Rp) and 10 days later. In the Rp less than 4 h group, about half of the initially abnormal segments showed complete improvement on quantitative wall motion analysis, which was more than in the Rp greater than 4 h and control groups. 2) In patients with acute myocardial ischemia, the correlation between thallium perfusion and regional wall motion was assessed semiquantitatively. In unstable angina, 5.8% of the ventricular wall segments showed dissociation between perfusion and wall motion (well-perfused asynergy). These segments had abnormal wall motion although perfusion was maintained, and were thought to be areas of stunned myocardium. 3) Fourteen dogs were studied using thallium and 123I-beta-methyliodophenyl pentadecanoic acid (BMIPP) fatty acid imaging to evaluate the relationship of perfusion to metabolism. In the reperfusion model, mismatching of the pattern of thallium and BMIPP uptake was observed. Reperfused myocardium probably has an increased triglyceride content, which is related to the degree of myocardial viability. In conclusion, stunned myocardium may be correctly diagnosed acutely on the basis of alterations in its perfusion, metabolism, and function by using radionuclide cardiac imaging. PMID- 1942497 TI - Stunned myocardium and sympathetic denervation--clinical assessment using MIBG scintigraphy. AB - To evaluate the clinical relationship between stunned myocardium and the sympathetic nervous system, 6 patients who had stunned myocardium accompanied by T wave inversion underwent simultaneous 123I-metaiodobenzyl guanidine (MIBG) scintigraphy and thallium scintigraphy. All patients showed abnormal filling defects on the MIBG scintigrams in the areas with stunned myocardium but the thallium scintigrams were almost normal. The extent of the defects in these 6 patients was determined on the MIBG scintigrams using a Bull's eye display. The defects were found to be larger than those in 4 patients with angina pectoris, and those in 4 patients who had previously shown T wave inversion but had a normal electrocardiogram at the time of examination. Thus, it is suggested that sympathetic denervation is one of the mechanisms causing stunned myocardium. PMID- 1942498 TI - Relation of change in wall motion and glucose metabolism after coronary artery bypass grafting--assessment with positron emission tomography. AB - Regional myocardial glucose metabolism was assessed by positron emission tomography (PET) in stunned myocardium. PET perfusion and metabolic imaging using N-13 ammonia and F-18 deoxyglucose (FDG) was performed before and 5-7 weeks after coronary artery bypass grafting (CABG) in 23 patients with coronary artery disease. Of 22 asynergy segments showing increased FDG uptake preoperatively, the postoperative PET showed a decrease in FDG uptake in 16 segments (73%) and persistent uptake in 6 segments (27%). The improvement in asynergy was observed in all of the segments showing postoperative decrease in FDG uptake, while it was observed in only 50% of those with persistent FDG uptake (p less than 0.01). On the other hand, 4 of 5 segments showing a new FDG uptake postoperatively revealed deterioration of wall motion abnormality. These data suggest that an increase in exogenous glucose utilization may often persist in postischemic myocardium. Improvement in regional function seems to be associated with the improvement in metabolic abnormality after CABG. PMID- 1942499 TI - Serial transcardiac lactate metabolism in post-reperfused stunned myocardium in evolving myocardial infarction. AB - To elucidate the relationship between lactate metabolism following reperfusion and restoration of left ventricular (LV) function, we assessed serial changes in transcardiac lactate metabolism following reperfusion therapy in 67 patients admitted to hospital within 6 h of the onset of acute anteroseptal myocardial infarction. Left ventriculograms taken about 30 min after reperfusion therapy revealed marked dyskinesis in the anteroapical region in all subjects. According to the regional ejection fraction (rEF), determined 4 weeks later as an index of LV function, patients were divided into 3 group: 1) Restored LV group: 28 patients with reperfusion and restored LV function (rEF greater than 30%); 2) Poor LV group: 26 patients with reperfusion but poor LV function (rEF less than 30%); 3) Failure group: 13 patients with failed reperfusion and occluded left anterior descending coronary artery. Although there was no difference in elapsed time and time to peak creatine phosphokinase (CPK) between the former 2 groups, the Restored LV group demonstrated lower peak CPK values, suggesting that these patients had less myocardial injury. Immediately after reperfusion, both groups showed transcardiac lactate production. In the Restored LV group, aerobic lactate metabolism was restored early after reperfusion (at 6 h), while in the Poor LV group prolonged anaerobic lactate metabolism was observed. These results suggest that an early restoration of aerobic metabolism might be a sign of stunned and viable myocardium, and a sustained lactate production might relate to a sustained process of myocardial injury. PMID- 1942500 TI - [On the standards for anesthetic safety]. PMID- 1942501 TI - [Comparison of the effect of propofol and that of pentobarbital on behavioral responses to somatic and visceral stimuli in rats]. AB - The behavioral responses to tail-flick and colorectal distension after intraperitoneal administration of either small or large dose of propofol as well as of pentobarbital were studied in rats. Immediately after baseline testing, animals were randomly divided into four groups; propofol groups of 50 mg.kg-1 (n = 4) or 100 mg.kg-1 (n = 4) and pentobarbital groups of 10 mg.kg-1 (n = 4) or 20 mg.kg-1 (n = 4). Both tests were repeated every 10 minutes for 1 hour in each group. There were no changes in the thresholds of colorectal distension and tail flick latencies in those animals receiving small doses of propofol and pentobarbital. The thresholds for colorectal distension following administration of large doses of propofol and pentobarbital had greatly increased at 10 minutes and this increase persisted for about 30 minutes although it declined gradually. In contrast, the state of high sensitivity to tail-flick test was seen in the large dose groups of both drugs. It is concluded that there are no pharmacological differences between propofol and pentobarbital in behavioral responses to somatic and visceral stimuli in rats. PMID- 1942502 TI - [Nicardipine inhibits phosphate reabsorption regardless of glomerular filtration rate in hypertensive surgical patients]. AB - The author investigated the mechanism of diuretic effect of a calcium entry blocker of dihydropyridine derivative, nicardipine, in comparison with furosemide given during surgical interventions on 13 hypertensive patients. In another group of 16 surgical patients, a bolus of furosemide 10 mg is given for a control. In hypertensive patients, intravenous nicardipine in doses of 1 to 2 micrograms.kg 1.min-1 produced normotensive state during surgery accompanied by significant diuresis. The extent of diuresis produced by the two agents, nicardipine and furosemide, was similar in urine volume and sodium excretion rate. On the contrary, the fractional excretion of PO4 (FEP) increased from 9.4 +/- 5.5% to 29.8 +/- 10.4% only after nicardipine. Plasma levels of electrolytes (Na, K, Ca, PO4) and parathyroid hormone showed no change during the study in the two groups. Nicardipine induced diuresis and phosphaturia in all hypertensive surgical patients regardless of the levels of creatinine clearance, plasma PO4 and parathyroid hormone. As organic phosphate reabsorption occurs largely in the proximal tubule, increased phosphaturia suggests that the proximal tubule is activated by nicardipine. PMID- 1942503 TI - [Cerebral effects of isoflurane-induced or PGE1-induced hypotension in dogs]. AB - The cerebral effects of hypotension induced by inhalation of increasing concentrations of isoflurane or intravenous administration of prostaglandin E1 (PGE1) were studied in 15 dogs anesthetized with 1% isoflurane and 50% nitrous oxide during normocarbic (PaCO2 approximately 39 mmHg) and normothermic (37.5 degrees C) condition. Mean arterial pressure (MAP) was decreased stepwise to 25, 40, and 55% of its baseline values. Cerebral blood flow (CBF) was measured using the venous outflow technique. Cerebral metabolic rate for oxygen (CMRO2), cerebral metabolic rate for glucose (CMRgl) and oxygen/glucose index (OGI) were calculated, and cerebrospinal fluid pressure (CSFP) and EEG were also recorded at each decrement in MAP and after resuming the control condition. The CBF, CMRO2, CMRgl, OGI and CSFP responses related to hypotension showed no significant changes from baseline values in both methods. However, CBF values in isoflurane induced hypotension at 25% and 40% reduction of MAP were significantly higher than those in PGE1-induced hypotension. By increasing concentration of isoflurane, EEG changed from continuous fast wave to high amplitude (100 microV) slow wave (4-6 Hz) and typical burst suppression observed in 3 of 8 dogs. In contrast, no significant EEG changes were seen during PGE1-induced hypotension. These results suggest no adverse effect of isoflurane- and PGE1-induced hypotension on cerebral metabolism or function. PMID- 1942504 TI - [Effect of superimposed high frequency oscillation on pulmonary edema induced by intrapulmonary injection of hydrochloric acid in dogs]. AB - Effect of superimposed high frequency oscillatory ventilation on pulmonary gas exchange was investigated in seven anesthetized and paralyzed dogs with pulmonary edema induced by intrapulmonary injection of hydrochloric acid. Efficacy of the ventilatory modes (HFO:6 Hz and 12 Hz) was evaluated observing changes in ventilation-perfusion mismatch, which was demonstrated by using six inert gas elimination method. The ventilation with 6 Hz HFO had no significant effect on PaO2, true shunt, and perfusion distribution. With 12 Hz HFO, PaO2 showed a tendency to increase from 57 +/- 18 mmHg at IPPV to 144 +/- 117 mmHg (0.05 less than P less than .01), and the true shunt decreased from 42.2 +/- 29.0% at IPPV to 16.6 +/- 25.8% (P less than 0.05). However, no change appeared in the perfusion distribution. During the ventilation with 12 Hz HFO increased mean airway pressure produces a PEEP-like effect, which may improve the pulmonary gas exchange by opening small airways, namely a decrease in the true shunt rather than an improvement in the ventilation-perfusion maldistribution. PMID- 1942505 TI - [Preoperative evaluation of patients with disturbed respiratory functions (II)]. AB - We analyzed correlation between postoperative pulmonary complications and pre operative pulmonary functions. In patients with severely disturbed respiratory functions; i.e. % VC of under 30% or % FEV1 of under 30%, for the past 6 years. Pulmonary complications developed in 6 of the 18 patients studied (33.3%). Of the 9 patients with preoperative PaO2 of under 70 mmHg, pulmonary complications developed in 6 patients (66.7%). Of the 7 patients with preoperative PaCO2 over 50 mmHg, pulmonary complications developed in 5 patients (71.4%). We found that postoperative pulmonary complications correlate well with preoperative PaO2 and PaCO2, in patients with severely disturbed respiratory functions. PMID- 1942506 TI - [A retrospective study on postoperative pulmonary dysfunction as a function of the surgical injury]. AB - Pre- and postoperative pulmonary function tests were studied retrospectively in 80 patients. They were divided into one of 5 groups: 1, surgery of the upper abdomen; 2, surgery of the lower abdomen; 3, surgery of the body surface; 4, thoracic surgery; and 5, extensive abdominal surgery. Postoperative pulmonary function tests were performed when the patients recovered to be able to sit up. The time necessary to reach this stage varied from 8 th postoperative day in groups 1, 2, and 3 to 24 postoperative day in groups 4 and 5. FRC, %FEV1.0, V25, and TV were unchanged in groups 1 and 2 postoperatively. There was a significant reduction in VC to 81.6 +/- 24.1% and 89.1 +/- 13.3% of the preoperative value in group 1 and 2, respectively. A significant decrease in TLC and a significant increase in RV were observed in group 1. The changes in pulmonary mechanics can be attributed to the muscle dysfunction during inspiratory and expiratory effort. A decrease in TLC and an increase in RV were also observed in group 2. All of the pulmonary function variables remained unchanged postoperatively in group 3. The restrictive pulmonary dysfunction with significantly reduced VC was observed in groups 4 and 5. V50 and V25 were significantly decreased in group 4. These changes could be attributed to the use of the extracorporeal circulation during cardiac surgery and the postoperative mechanical ventilation. TLC decreased significantly in groups 4 and 5, and RV increased significantly in group 5, but unchanged in group 4. The results indicate that the expiratory muscles function normally following the thoracic surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942507 TI - [Effect of halothane, fentanyl and ketamine on the threshold for the passage of venous air embolism through lungs in dogs]. AB - Effect of halothane, fentanyl and ketamine on the passage of air injected bolus across the pulmonary circulation was studied in dogs using transesophageal M-mode echocardiography. Dogs in Group 1 (N = 5) were anesthetized with halothane and then halothane with fentanyl. At least 3 weeks later the dogs were anesthetized with fentanyl and then fentanyl with halothane. The same procedure was utilized in group 2 (N = 4) using halothane and ketamine. The doses of halothane, fentanyl and ketamine were 1% inspired concentration, 100 micrograms.kg-1 followed by 1 microgram.kg-1.min-1 iv, and 10 mg.kg-1 followed by 0.1 mg.kg-1.min-1 iv, respectively. The threshold for bolus air detection during halothane, fentanyl and ketamine alone were 0.05, 0.5 and 0.2 ml.kg-1, respectively. The threshold during fentanyl administration, but not during ketamine administration, was significantly higher than that during halothane. The addition of halothane to fentanyl or ketamine lowered the threshold to the same level as with halothane alone, and the addition of either fentanyl or ketamine to halothane made no difference. Although there was no difference in baseline shunt fraction resistance index [PVRI/(Qs/Qt)] during administration of each anesthetic, every air injection decreased shunt fraction resistance index during halothane without fentanyl or during halothane with or without ketamine, and increased it during fentanyl administration. PMID- 1942508 TI - [Epidural midazolam for treatment of postoperative pain]. AB - Postoperative pain relief and sedation with epidural midazolam were studied. Twenty-one patients for elective upper abdominal surgery were divided into 3 groups. Epidural catheter was inserted into thoracic epidural space before induction of general anesthesia. In each group, either 10 ml saline only, midazolam 0.05 mg.kg-1 + 10 ml saline, or midazolam 0.1 mg.kg-1 + 10 ml saline was injected into epidural catheter for complaint of pain in recovery room. For 120 minutes after epidural injection, blood pressure, heart rate, respiratory rate, serum concentration of midazolam, and sedation score were monitored. In midazolam injected groups, only slight changes were seen in blood pressure, heart rate, and respiratory rate. Sedation score was graded from 1 to 6:1 means complete sleep, and not responded to verbal command, 6 means agitated and many complaints. Midazolam 0.1 mg.kg-1 + 10 ml saline group had the lowest score, and saline 10 ml group had the highest score. Prolonged sedation and pain relief were obtained in midazolam injected group, especially 0.1 mg.kg-1 + 10 ml saline group. Serum midazolam concentrations were lower than 200 ng.ml-1. These values were considered as the lower limit for sedation by intravenous administration. In conclusion, epidural midazolam was useful for postoperative pain relief. The mechanism is considered to involve spinally mediated CNS action or direct spinal action. PMID- 1942509 TI - [Does methylprednisolone potentiate the effects of dobutamine during thoracic epidural analgesia?]. AB - The cardiovascular effects of dobutamine (DOB) combined with methylprednisolone (MP) were studied during thoracic epidural analgesia (TEA) in 59 patients undergoing operations on upper abdomen. To establish TEA, 8-10 ml of lidocaine 20 mg.ml-1 was injected into the epidural space through the T8-T9 interspace. The patients was intubated after fentanyl 0.2 mg, thiopental 3 mg.kg-1 and vecuronium 0.2 mg.kg-1. Anesthesia was maintained with 67% N2O, 33% O2 and 0.6% enflurane and DOB was infused at a rate of 5 micrograms.kg-1.min-1 during the surgical operation. Systolic blood pressure and urinary output after TEA did not decrease in the two groups, pretreated with MP 5 mg.kg-1 one hour or immediately before TEA, but decreased in the control group without MP injection. Heart rate showed no significant changes after TEA in all groups. We conclude that MP may potentiate the cardiovascular effects of DOB during TEA. PMID- 1942510 TI - [Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--8. Hepatic and renal functions following prolonged surgical operation of over 10 hours]. AB - Forty-four patients were studied to evaluate their postoperative hepatic and renal functions on 2nd to 4th and 7th to 10th postoperative days as judged by serum GOT, GPT, BUN and creatinine levels. The patients were divided into two groups. Twenty two patients received total intravenous anesthesia with droperidol, fentanyl and ketamine (FK group). The remaining 22 patients were given conventional enflurane-nitrous oxide anesthesia. The two groups were comparable concerning age, body weight, sex distribution, performed operation, operation time and anesthesia time. In the total intravenous group, fluid given and urine output were significantly larger than those of the enflurane group, and the amounts of blood loss and blood given tended to be greater but insignificantly in the total intravenous group than in the enflurane group. In both groups, postoperative S-GOT levels increased significantly and those of the enflurane group were significantly higher than those of the FK group on 2nd to 4th postoperative days. In the enflurane group, postoperative S-GPT levels were significantly higher, but those of the FK group were not. S-GPT on 2nd to 4th postoperative days of the enflurane group were significantly higher than those of the FK group. As to serum BUN and creatinine, no significant differences were observed between the two groups. These data suggest that FK is much more beneficial than enflurane anesthesia to protect hepatic functions, particularly when it is applied for prolonged surgical procedures. PMID- 1942511 TI - [Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--9. Control of intraoperative hypertension with diltiazem]. AB - Intraoperative hypertension over 160 mmHg systolic and sinus tachycardia over 100 bpm are often observed during total intravenous anesthesia with droperidol, fentanyl and ketamine. Fifty-seven surgical patients who developed hypertension over 160 mmHg systolic during various operative procedures under this type of anesthesia were given diltiazem intravenously to overcome the situation. Their blood pressure and heart rate decreased soon after the administration of diltiazem. The rate pressure product was reduced significantly. Neither preoperative hypertension nor difference of doses between 5 mg and 10 mg of diltiazem had any significant relationship with hypotensive effect of intravenous diltiazem. But the higher the systolic-pressure was just before the administration of diltiazem, the more effective diltiazem was. No adverse effects with this drug was observed. We can conclude that intravenous diltiazem in a dose of 5 mg or 10 mg may be repeatedly given to overcome hypertension or sinus tachycardia during this type of anesthesia without any adverse effects. PMID- 1942513 TI - [Effect of ulinastatin on microcirculation under excessive hemorrhage and fluid therapy]. AB - Microcirculation during excessive hemorrhage and fluid therapy under anesthesia with or without associated treatment by ulinastatin (urinary trypsin inhibitor) was studied by using the rabbit ear chamber. Sixteen rabbits were divided into 2 groups; 8 rabbits without ulinastatin treatment (C group) and rabbits treated with ulinastatin (U group). After blood withdrawal, hemodynamic disturbance appeared in both groups. But the catecholamine concentration showed no increase in either groups. Significant differences between the groups were found only in urinary output and microcirculation. These were well maintained during hemorrhage in the ulinastatin treated group. It is concluded that ulinastatin is effective in maintaining microcirculation during excessive hemorrhage and fluid therapy. PMID- 1942512 TI - [Changes in plasma endothelin in patients undergoing cardiac valve replacement under high dose fentanyl anesthesia]. AB - We measured plasma endothelin (ET) in 11 patients undergoing cardiac valve replacement under high dose fentanyl (116.6 +/- 15.4 micrograms.kg-1, mean +/- SD) anesthesia. Arterial blood samples were obtained: 1) before induction of anesthesia (control), 2) just before the start of cardiopulmonary bypass (CPB), and 3) just before the end of CPB. Endothelin levels were analyzed by radioimmunoassay based on double antibody method using Silica ODS suspension. ET concentrations in period 1, 2, and 3 were 3.0 +/- 1.1, 4.2 +/- 1.7 and 4.5 +/- 1.8 pg.ml-1 (mean +/- SD), respectively. There were no significant differences among these three values (P less than 0.05). The results suggest that under high dose fentanyl anesthesia, surgical stress including that of CPB might not affect ET concentration in plasma. PMID- 1942514 TI - [Voltage-dependent effects of lidocaine and its metabolite, monoethylglycine xylidide (MEGX), on maximum rate of rise (Vmax) of action potential upstroke in guinea-pig papillary muscles]. AB - We studied the effects of lidocaine and MEGX on the sodium current, using Vmax as an indicator, at an extracellular potassium concentration ([K]o) of 10 mmol.l-1, and compared the present results with those obtained at 5.4 mmol.l-1 [K]o in our previous study. At 10 mmol.l-1 [K]o, both lidocaine (10 micrograms.ml-1) and MEGX (10 micrograms.ml-1) significantly decreased the Vmax at the steady-state of 1 Hz, caused a significant rate-dependent decrease in Vmax, and slowed the recovery kinetics of Vmax. These effects of both agents were more prominent than those obtained at 5.4 mmol.l-1 [K]o, suggesting that MEGX as well as lidocaine produce voltage-or [K]o-dependent blocking effects on Vmax. PMID- 1942515 TI - [Changes in granulocyte elastase caused by the use of ulinastatin during anesthesia for renal transplantation]. AB - In patients with renal failure, releases of chemical mediators having inhibitory influences on organs and circulatory system have been observed. Therefore, in long-term dialysis patients, it is necessary to consider the biocompatibilities of the equipment for dialysis. On 13 cases of renal transplantations, we measured the pre- and post-operative changes of granulocyte elastase (GE) and evaluated the effect of ulinastatin. The renal transplanted patients receiving a long-term dialysis showed higher GE values than that of normal patients even before the operation. During the anesthesia, GE increased gradually and further increased after the operation. In patients given ulinastatin during anesthesia, the increase in GE during the operation was suppressed but an increase after the operation was observed. The renal transplanted patients are easily infectible. Therefore, it is useful to measure GE pre- and post-operatively for earlier diagnosis of the postoperative infection and septicemia. The administration of ulinastatin can inhibit the increase of GE. It seems that ulinastatin increases renal blood flow and improves renal function. PMID- 1942516 TI - [Utility of Bullard intubating laryngoscope with a special stylet in two cases of difficult tracheal intubation]. AB - The Bullard intubating laryngoscope is useful for cases of difficult tracheal intubation, but a skilled hand is needed to manipulate it. In two cases of difficult tracheal intubation, we used a recently improved Bullard intubating laryngoscope to which a special stylet is attached to introduce an endotracheal tube easily into the larynx. The difficulties of tracheal intubation were caused by micrognathia and trismus in one case and by restriction of neck movement and trismus due to ankylosing spondylitis in the other case. Using the Bullard intubating laryngoscope with the special stylet, intubation was done smoothly in both cases. This improved Bullard intubating laryngoscope is recommended for cases of difficult tracheal intubation. PMID- 1942517 TI - [Anesthetic management of a patient with Chubby Puffer syndrome]. AB - Chubby Puffer syndrome produces symptoms such as sleep apnea, cor pulmonale and upper airway obstruction due to adenotonsillar enlargement. We gave anesthesia for adenotonsillectomy in a 6-year-old boy with this syndrome. The child was massively obese. Anesthesia was induced with thiamylal, nitrous oxide and enflurane by monitoring SaO2. Tracheostomy was performed following orotracheal intubation because of possible difficult postoperative course. At the beginning of operation arterial blood studies showed hypoxemia. Positive end-expiratory pressure ventilation was effective to improve oxygenation. After adenotonsillectomy the symptoms were relieved. PMID- 1942518 TI - [Two cases of pulmonary edema during and after cesarean section]. AB - Pulmonary edema occurred during and after Cesarean section under general anesthesia in two pregnant women. They had no preoperative complication. After delivery, anesthesia was maintained with 66% N2O in oxygen and intravenous injection of pentazocine and diazepam. At the same time, 0.2 mg of methylergometrin was injected intramuscularly and 2,000 micrograms of prostaglandin F2 alpha was injected to the muscle of the uterus in order to induce uterine contraction. In one case, SpO2 dropped and airway pressure increased immediately after the administration. In another case, chest rale was auscultated on postoperative round at 2 hours after operation. The cases suggest that pulmonary edema was caused by a large quantity of oxytocics, which increased volume load on systemic circulation. PMID- 1942519 TI - [Statistical analysis of tracheobronchial foreign bodies]. AB - Incidence of foreign body aspiration in tracheobronchial tree is rare, however the foreign body aspiration can lead to severe illness and even death if not diagnosed and treated promptly. We retrospectively analyzed forty five patients who underwent ventilation bronchoscope under general anesthesia for suspected aspirated foreign bodies in our hospital. In thirty eight patients, foreign body was confirmed in tracheobronchial tree, while in seven patients foreign body was not confirmed with bronchoscope. The thirty eight patients ranged in age from 10 months to 73 years; the peak incidence of foreign body aspiration occurred in children under 3 years of age. Twenty five of thirty eight patients were male. Food or food derivatives were the causative agents in 68% of the patients, with 65% due to a portion of peanut. The foreign body was located in the right and left bronchus with almost equal frequency. The main symptoms were coughing (72%), wheezing (53%), and dyspnea (25%). The radiographic abnormality was seen in eighteen of thirty eight patients. A radio-opaque material was seen in 18%. Children at age 6 years of younger (90%) had been witnessed to choke on identifiable foreign body, but only 40% were diagnosed within 24 hours. Twelve of these children were treated unnecessarily for asthma, pneumonia, or so on. We conclude that it is most important to take history carefully considering the possibility of foreign body aspiration in the patients with coughing, wheezing, or dyspnea. PMID- 1942520 TI - [Multiple discriminant analysis for prognosis of refractory anemia]. AB - Forty-eight patients with refractory anemia (RA) were retrospectively analyzed for their prognosis and subclassified into three groups: 12 patients with hematological improvement (A), 23 patients with no changes (B), and 13 patients with progression to RAEB or acute leukemia (C). For all patients, the median survival were 49.2 months, and the rate of leukemic transformation was 16%. The median survivals were 60.6, 32.1, and 17.9 months, respectively, for groups A, B and C. The factors indicating poor prognosis were low reticulocyte counts, low neutrophil alkaline phosphatase activity, low% red cell utilization, high M/E ratio, high blast percentage in the bone marrow and cytological abnormalities in the granulocyte and megakaryocyte series. By using multiple discriminant analysis, we obtained a formula for the prognostic estimation with a discrimination probability of 62.5%. This formula could predict either the patients with good (Y greater than 0.85) or poor (Y less than 0.59) prognosis, and might be useful to select the treatment for this intractable anemia at the time of diagnosis. PMID- 1942521 TI - [The efficacy of VAD chemotherapy for refractory lymphoid malignancies]. AB - Thirty patients with refractory lymphoid malignancies [multiple myeloma (MM): 8, plasma cell leukemia (PCL): 2, acute lymphocytic leukemia (ALL): 5, chronic myelogenous leukemia in blast crisis: 1, chronic lymphocytic leukemia in blast crisis: 1, adult T-cell leukemia: 1, non-Hodgkin lymphoma (NHL): 9, Hodgkin's disease (HD): 3] were treated with VAD regimen (vincristine, doxorubicin, dexamethasone). Of 28 evaluable patients, 4 patients achieved complete response or remission [MM1, ALL1, NHL1, HD1], 10 attained partial response or remission [MM5, PCL1, NHL3, HD1], and 2 patients with MM attained minor response. The remission duration ranged from 1 month to over 14 months. The response rate was high in patients with MM (75%) and lymphoma (60%), however 4 patients with T-cell malignancies achieved no response except one with NHL. In three patients who showed resistance to VAD, diltiazem was administered in addition to VAD and one patient with MM had response. Atrio-ventricular block was also observed in one patient during the period of diltiazem administration. Nine patients developed documented infections, 5 of which suffered from candida infections. From these observations, we concluded that VAD regimen might be useful as a salvage therapy especially in patients with MM and lymphoma. PMID- 1942522 TI - [Clinical investigation on acute respiratory failure in patients with severe hematologic malignancy]. AB - Ten patients with severe hematologic malignancies (four with acute leukemia, three with multiple myeloma, one with prolymphocytic leukemia, one with malignant lymphoma and one with blastic crisis of chronic myelogenous leukemia) developed respiratory failure during the period between April 1986 and May 1990. Clinically, the patients manifested high-fever, dyspnea refractory to oxygen therapy, diffuse pulmonary rales and severe hypoxemia without evidence of cardiogenic pulmonary edema. Chest roentgenograms displayed diffuse alveolar infiltrates. Respiratory failure occurred as early as 48 hours and as late as 66 days after the administration of intensive anti-neoplastic chemotherapy. At that time leukocyte count was between 100/microliters and 54,900/microliters. Marked leukocytosis was observed in two patients with AML and PLL. Respiratory failure was preceded by sepsis in one patient with AML and by pneumonia in nine patients. DIC was diagnosed in four patients. All patients treated with high dose methyl prednisolone (mPSL) within 12 hours after the onset of respiratory failure. Only one patient required assisted ventilation. High dose mPSL had significant effect on seven of ten patients. But three patients died from progressive respiratory failure, sepsis, pneumonia and multi-organ failure. PMID- 1942523 TI - [An improved method for biochemical measurement of the activity of neutrophil alkaline phosphatase and its application to myeloproliferative disorders]. AB - The activity of neutrophil alkaline phosphatase (NAP) has been commonly measured semi-quantitatively by rating the intensity and number of positive granules on cytochemical staining. This method has been widely adopted because of quickness and simplicity. However, the scoring system, in itself, seems to have several demerits that it has poor reproducibility and has limit for expressing enhanced NAP activity. We improved previous methods for measuring biochemical activities of NAP. Our method was as quick and simple as cytochemical measurement and had more excellent reproducibility. Biochemical activities of NAP ("b-NAP"s) in extract from 2 x 10(6) neutrophils of 7 patients with polycythemia vera were about six times as high as those of 7 cases of essential thrombocythemia [144.8 +/- 33.2, 23.1 +/- 9.1 U, respectively], while NAP scores in the former showed only twice the degree of elevation of those in the latter. These observations suggest that our method can represent high NAP activity more exactly than NAP score and may be a potential tool in differentiating polycythemia vera from essential thrombocythemia. PMID- 1942524 TI - [Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia]. AB - We reported the results of 6 allogenic bone marrow transplantation (BMT) and 3 autologous BMT for patients with Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) by Nagoya BMT group. Two of six patients who received allogenic BMT have continued complete remission (CR) on +639 days and +1,597 days. Four of six patients relapsed on +134, +203, +216, and +267 days. Two patients with a disease-free survival for a long time had both acute and chronic GVHD. It is suggested that graft-versus-leukemia (GVL) effect might prevent the relapse. On the contrary, one patient who received with monoclonal antibodies plus complement-treated autologous bone marrow is free of leukemia on +439 days. Our results suggest the follows. 1) We do chromosomal analysis at initial diagnosis in all cases to do BMT in first CR. 2) We intensify the conditioning regimen for BMT. 3) We study on application of GVL effect to prevent the relapse. 4) We establish the best purging method to eradicate residual leukemic cells for autologous BMT. 5) We do allogenic BMT using HLA-matched unrelated donor for patients without related donor. PMID- 1942525 TI - [Clinical features of atypical refractory anemia (RA)]. AB - Twenty-three patients with bicytopenia or pancytopenia were retrospectively studied. The patients with underlying disorders, blast count of more than 5% on bone marrow (BM) aspirate, blast count of more than 1% on peripheral blood or ringed sideroblast count of more than 15% on BM aspirate were excluded. According to Yoshida's criteria, 23 patients were classified into 6 subtypes [AA (aplastic anemia)1: typical AA, AA2: atypical AA, MDS (myelodysplastic syndrome)3: typical RA (refractory anemia, MDS4-6: atypical RA], and AA1 7 cases; AA2 2 cases; MDS3 5 cases; MDS4 1 case; MDS5 2 cases; MDS6 6 cases. To clarify the clinical features of atypical RA group (MDS4-6), we investigated ferrokinetics, RBC life span, karyotype, serum Epo (erythropoietin) concentration, response to therapy and prognosis. Results were as follows: 1) all three RA patients who were younger than 30 years old were included in atypical RA group, 2) in ferrokinetics study PID (plasma iron disappearance time) values of MDS4 and MDS6 patients ranged between those of AA1 and those of MDS3 patients (5 of 7 patients), 3) two cases who developed leukemia belonged to typical RA group, 4) patients with atypical RA showed response to therapy and their prognosis were better than those with typical RA. These observations suggest that atypical RA have different clinical features from typical RA. PMID- 1942526 TI - [An autopsy case of acute mixed lineage leukemia with monosomy 7 in a child]. AB - A five-year-old boy initially diagnosed common ALL was developed to acute myelomonocytic leukemia. At onset, the bone marrow was hypercellular and 77% of the cells were blasts, mainly lymphoblast-like cells and cytogenetic study demonstrated 45, XY, -7 in all blasts. Cytochemically most of those blasts were negative for peroxidase, sudan black B, alpha-NB esterase staining. The immunological phenotype was J5 (CD10)+, I2 (HLA-DR)+, SmIg-, CyIgmu-, Leu1 (CD5) , OKT11 (CD2)-, MY7 (CD13)-, suggesting common ALL. Eight months later, the bone marrow cells were occupied with large sized blasts which were almost positive for peroxidase stain and the cells showed coexpression of Mo1 (CD11b)+, MY4 (CD14)+, MY7+, MY9 (CD33)+, MCS2 (CD13)+, I2+, J5-, B4 (CD19)-, Mo2 (CDw14)-, at relapse. He died 2 years and 6 months after his initial diagnosis. An autopsy was performed which revealed generalized infiltration of leukemic cells and aspergillosis of the lung. In general, monosomy 7 is associated with myelodysplastic syndrome in childhood, and is terminated to acute myeloblastic leukemia. In this case, bone marrow blasts demonstrated monosomy 7 cytogenetically, and this case was considered as an acute mixed lineage leukemia of bilineal type. And this case proved that a monosomy 7 can also be terminated to acute mixed lineage leukemia with both lymphoid and myeloid phenotypes. PMID- 1942527 TI - [Acute megakaryoblastic leukemia developing 11 years after diagnosis of essential thrombocythemia]. AB - A 57-year-old man was diagnosed to have essential thrombocythemia (ET) in July 1977. He was doing well with continual medication of carboquone but was hospitalized because of slight unconsciousness and gait disturbance in May, 1988. His laboratory data were as follows: WBC count 81,600/microliters with 55% of blasts with cytoplasmic blebs, Hb 10.2 g/dl, and platelet count 2.6 x 10(4)/microliters. Bone marrow aspiration revealed hypercellular marrow with 72.8% blasts. Chromosomal analysis showed tetraploidy with 7p+ and 19p+. Cytochemistry of blasts showed the positivity for platelet peroxidase and CDw 41. The diagnosis of acute megakaryoblastic leukemia was made. Meningeal leukemia was also suspected by the cerebrospinal fluid data, and cytarabine was intrathecally injected. Then the percent of blasts of peripheral blood gradually decreased and the data of cerebrospinal fluid improved. However, several days later the patient became comatose probably due to cerebral bleeding, and died. In this case, two possibilities were considered (1) that a blastic transformation to acute leukemia from ET, and (2) that a secondary leukemia developed as a result of the chemotherapy, independently of ET. Since there was no evidence of myelodysplastic syndrome, it was concluded that this case represented a blastic transformation of ET. PMID- 1942528 TI - [T-cell type non-Hodgkin's lymphoma associated with eosinophilia]. AB - A 65-year-old man was admitted to our hospital in January 1990, because of weakness of upper limbs. On admission he was found to have generalized lymphadenopathy and leukocytosis. His WBC count was 40,900/microliters with 88% eosinophils. The bone marrow showed an increased number of eosinophils and their precursors but no other abnormalities. A diagnosis of non-Hodgkin's lymphoma (diffuse, medium sized cell type) was made by biopsy of his inguinal lymph node. The result of marker analysis was consistent with CD3+4+8-. The antibody to human T-lymphotropic virus type I was negative. A stomach biopsy revealed lymphoma cell infiltration. Extensive studies to identify the cause of the eosinophilia were undertaken, with consistently negative results. Combination chemotherapy was begun, and resulted in a dramatic resolution of the eosinophilia and the lymphadenopathy. The association of hypereosinophilia with non-Hodgkin's lymphoma is unusual. We report a patient with eosinophilia and non-Hodgkin's lymphoma, and discussed its possible etiology. PMID- 1942529 TI - [Primary plasma cell leukemia associated with hypercalcemia]. AB - A 34-year-old male was admitted to our hospital because of anorexia and nausea in September, 1987. On admission, anemia, thrombocytopenia and hypercalcemia were observed, and the peripheral blood showed leukocytosis with atypical plasma cells (50%). Bone marrow aspiration showed hypercellularity, with a presence of atypical plasma cells (82%). The M-type protein in the serum and urine was identified as lambda Bence Jones protein by immunoelectrophoresis. On systemic skeletal X-rays, osteolytic lesions were not detected. Thus, a diagnosis of plasma cell leukemia associated with hypercalcemia was made. Hypercalcemia was treated successfully with overhydration. However the disease was refractory to combination chemotherapy, and at 10 months after diagnosis, he died of septic candidiasis. Hypercalcemia associated with plasma cell leukemia in its initial stage is rare. PMID- 1942530 TI - [Transient B lymphocytosis associated to hepatitis B after allogeneic bone marrow transplantation]. AB - A 42-year-old male suffered from AML (M2) and achieved remission with chemotherapy. After that, he was successfully treated with allogeneic bone marrow transplantation. About eight months later, jaundice and general malaise developed and diagnosis of acute hepatitis B type was made based on laboratory findings. After 3 months of a conservative therapy, he recovered from the disease. During the clinical course of the hepatitis, B lymphocytes were increased to about 70% of peripheral blood lymphocytes (PBLs) transiently, and furthermore CD5 positive B lymphocytes occupied 12% of the PBLs at that time. This B lymphocytosis disappeared gradually along with the improvement of the hepatitis. The remarkable increase of B lymphocytes in PBLs was considered to be an abnormal reaction induced by HB virus infection, when his immune system was in the recovering phase after bone marrow transplantation. PMID- 1942531 TI - [Progression from Crow-Fukase syndrome with double gammopathy (IgM-kappa, IgG lambda) to primary macroglobulinemia]. AB - This report deals with a case of double gammopathy (IgM-kappa, IgG-lambda) with Crow-Fukase syndrome, which developed into primary macroglobulinemia four years after the diagnosis. In May 1980, a 74-year-old woman was admitted to the hospital because of a rapid progression of peripheral neuropathy. The patient was diagnosed as having Crow-Fukase syndrome from the following data: albumin cytologic dissociation of cerebrospinal fluid, peripheral edema, diffuse hyperpigmentation of the skin, diabetic glucose intolerance, serum double gammopathy (IgM-kappa, IgG-lambda) and hepatomegaly. The administration of prednisolone yielded the improvement of neuropathy. In December 1984, serum IgM level was increased from 104 mg/dl to 3,025 mg/dl. Plasma cells in the bone marrow increased in the percentage from 5.6% to 18.4%, and then Bence Jones protein (kappa type) was excreted in the urine. No antibody activity to myelin antigens was detected in the serum. The patient died of cerebral infarction in 1985. At postmortem examination, lymphomatous involvement was found in the jejunum. At the immunohistological examination of the tumor specimens, the morphology and the distribution of IgM- and IgG-positive cells corresponded to that of kappa- and lambda-positive cells, respectively. A small number of cells containing both kappa and lambda light chains were also demonstrated. It seems likely that IgM (kappa)- and IgG (lambda)-positive cells were derived from the common precursor cells. PMID- 1942532 TI - [Myelodysplasia predominantly involving in megakaryocytic lineage successfully treated with low-dose Ara-C]. AB - A 17 year old male was admitted because of pancytopenia. Bone marrow aspiration revealed myelodysplasia, no increase of blast cells and excessive expansion of megakaryocytic lineage. Although mild increase of bone marrow reticulin fiber was observed, no hepatosplenomegaly was recognized. Therefore he was diagnosed as refractory anemia (RA) or MDS with myelofibrosis and treated with low dose Ara-C regimen. Remission was achieved in June 1987, but the relapse occurred in Oct. 1987. His bone marrow at the relapse showed more remarkable dysplastic change than before. Sequential bone marrow examinations thereafter, revealed an increase of megakaryocytic lineage, especially immature dysplastic megakaryocytes, leading to the appearance of the abnormal megakaryoblasts (detected with anti GP IIb/IIIa antibody) as well as uncharacterized blast cells in his terminal stage. Transformation from MDS to megakaryocytic leukemia was strongly suggested. He died of severe pneumonia in March 1989. The invasion of abnormal immature megakaryocytic cells including megakaryoblasts was observed in liver, spleen and lymph nodes at autopsy. There are several reports on cases having a common hematological features such as 1) pancytopenia in peripheral blood, 2) myelodysplasia, 3) excessive growth of megakaryocytic lineage, 4) myelofibrosis without hepatosplenomegaly, although other clinical features were different. We propose all these cases should be reviewed at the point of MDS mainly involved in megakaryocytic lineage. PMID- 1942533 TI - [Multiple myeloma with hemolytic anemia and thrombocytopenia]. AB - We report a 59 year old female patient who was diagnosed as having IgG kappa myeloma with hemolytic anemia and thrombocytopenia simultaneously. Although M protein was suspected to contribute to the hemolysis, the IgG purified from the patient's serum did not bind to red blood cells. Therefore, massive non-specific binding of M-protein to blood cells might contribute to high levels of red blood cell-associated IgG and platelet-associated IgG in the patient. PMID- 1942534 TI - [Remarkable improvement of anemia by administration of recombinant human erythropoietin in a patient with aplastic anemia]. AB - A 69-year-old female was admitted for pancytopenia. The hematological examination showed leukocytes 1,800/microliters, hemoglobin 5.3 g/dl and platelets 9.6 x 10(4)/microliters. A bone marrow aspiration revealed hypoplasia, but no abnormal cells. Serum erythropoietin titer was 5,100 mU/ml. Diagnosis of aplastic anemia was made. She received 400 ml of blood transfusion twice, and was then treated with recombinant human erythropoietin (rHuEPO) (12,000 U/day) three times a week for eight weeks. Hemoglobin level gradually increased to the level of 12.0 g/dl. This case suggests that there are some cases of aplastic anemia which can respond to treatment with rHuEPO. PMID- 1942535 TI - [IgG lambda-type multiple myeloma associated with myelofibrosis accompanied by thrombocytosis]. AB - A 72-year-old male had complained of right back pain and bleeding from his tongue. He was admitted to our department on May 18, 1989. Physical examination revealed hepatosplenomegaly. Peripheral blood findings were as follows: RBC was 3.80 x 10(6)/microliters. Hb 12.2 g/dl, Ht 36.5%, platelet count 735 x 10(3)/microliters, WBC 22,100/microliters, leukoerythroblastosis present. Neutrophil alkaline phosphatase score was normal. Serum vitamin B12 and plasma platelet-derived growth factor level were elevated. Skeletal X-ray revealed multiple punched-out lesions at the 8th thoracic vertebra, and 6th and 8th ribs. Serum IgG level was 3,900 mg/dl. Serum immunoelectrophoresis revealed IgG lambda type M-protein. Because he complained of severe cervical pain, and skeletal X-ray examination revealed the fracture of 6th cervical vertebra, the operation was performed to remove the lesion. Biopsy of cervical lesion revealed plasmacytoma. M-protein was decreased and the size of the tumor was reduced after treatment with VCAP (vincristine, cyclophosphamide, adriamycin, prednisolone) regimen and interferon-alpha for multiple myeloma. PMID- 1942536 TI - [The changes in von Willebrand factor multimer in a course of thrombotic thrombocytopenic purpura]. AB - A 51 year-old woman with severe thrombocytopenia, hemolytic anemia, renal failure and loss of consciousness, and significant decrease in plasma large multimer of von Willebrand Factor (vWF) was diagnosed as having thrombotic thrombocytopenic purpura (TTP). She was treated with plasma exchange, anti-platelet agents and steroids. Although she showed temporary improvement and return of vWF multimer to a normal level, her symptoms reappeared, vWF large multimer level showed a remarkable increase, and she died because of pulmonary bleeding. It would be important that the vWF multimer bands changed in the course of TTP. PMID- 1942537 TI - [Torsade de pointes ventricular tachycardia in a patient with acute myelocytic leukemia]. AB - The anti-leukemic antibiotics, anthracyclines, are most effective agents in the treatment of acute leukemia. However, they have severe cardiac toxicities, which ordinarily shows dose-dependency, but sometimes produce acute cardiomyopathy. We experienced Torsade-de-pointes arrhythmia during the treatment of acute myelocytic leukemia (AML); The patient was a 28 year old woman and had an AML-M1. After the short course administration of daunorubicin (total 90 mg/m2) and aclarubicin (total 219 mg/m2), she suffered from an attack of Torsade-de-pointes ventricular tachycardia and passed away, since any treatment against ventricular arrhythmia was not effective. Autopsy studies revealed degeneration and atrophy of cardiac muscle in the area around His's bundle, which suggested an anthracycline-induced cardiac toxicity. PMID- 1942538 TI - [Plasma PAI-1 levels in patients with various tumors with or without metastasis]. AB - Recently, much interest has focussed on fibrinolysis in malignant tumors. In our previous study, we showed that t-PA antigen was significantly increased in plasma from patients with malignant tumors with metastasis. In our present study, we measured plasminogen activator inhibitor-1 (PAI-1) levels in plasmas from patients with various tumors. PAI-1 antigen was measured by means of enzyme immuno assay in plasma from 64 consecutive patients with a variety of malignant tumors. Patients were subdivided into two groups, one with (n = 47) and without (n = 17) metastasis. In the group with metastasis except for lung cancer, PAI-1 antigen level was increased compared to age-matched control subjects, while in the group without metastasis, PAI-1 antigen level was normal. PMID- 1942540 TI - [Flow cytometric analysis of platelets in patients with Glanzmann's thrombasthenia]. AB - Platelets from 10 patients with Glanzmann's thrombasthenia (7 patients with type I and 3 with type II) and their 18 family members (11 parents, 6 siblings and one daughter) were analyzed by flow cytometry using 3 different commercially available FITC-labeled monoclonal antibodies. The amount of platelet GPIIbIIIa was calculated by using the ratio of the fluorescence intensity of the mean channel in comparison to normal platelets. The amount of platelet GPIIbIIIa was lower than 19% in 6 patients with type I and one patient with type II thrombasthenia. One type I patient had a 46.5% GPIIbIIIa amount as assessed using the monoclonal antibody TP80 (Nichirei Corp. Japan) which recognized GPIIb, although the other 2 antibodies showed an amount of less than 5%. One type II patient showed the following results: 30.9% (TP80), 28.2% (P2 antibody, Immunotech, France), and 3.9% (PLT1, Coulter Immunology, USA). The remaining type II patient consistently showed a normal amount of platelet GPIIbIIIa using all antibodies, appeared to be a variant form of thrombasthenia. The parents of type I patients had a significantly lower amount of platelet GPIIbIIIa compared to normal and 2 siblings of type I patients were diagnosed as heterozygotes. These findings suggest that Glanzmann's thrombasthenia is more heterogeneous than we have previously suspected, and that flow cytometric analysis using different monoclonal antibodies is a useful tool for identifying those heterogeneities and for the detection of type I carriers. PMID- 1942539 TI - [Parallel loss of c-FMS and GM-CSF genes in myeloid leukemias with 5q chromosome]. AB - DNA contents of c-FMS and GM-CSF genes were analyzed by densitometer in nine patients with myelodysplastic syndrome or acute myeloid leukemia associated with abnormality of chromosome 5. Five patients with deletion in the long arm of chromosome 5 had loss of both c-FMS and GM-CSF genes. These findings suggest that c-FMS oncogene and GM-CSF gene locating in the critical region on chromosome 5 seem to have an important role in the process of leukemogenesis. PMID- 1942541 TI - [Hereditary hemorrhagic telangiectasia associated with von Willebrand's disease; literature review]. AB - A 23-year-old female was admitted to our hospital in July 1987, because of cutaneous macular telangiectasia on her extremities and hypermenorrhea. In 1983, she began to notice small red spots on her palms. During next several years, these telangiectasia increased in number and spread all over her body. In 1986, she had a history of melena and prolonged bleeding after dental extraction. Her lower legs have turned red purple during the gait for a long time. Her older brother and two paternal cousins have experienced frequent epistaxis. The hemostatic laboratory data revealed prolonged IVY bleeding time and APTT, impaired capillary fragility, decreased vWf:Ag and VIII:C levels, depressed Rcof and severe decreased platelet adhesiveness, vWf mobility on two-dimensional crossed immunoelectrophoresis was normal. Platelet aggregation was reduced after addition of ristocetin and collagen. This case was diagnosed Osler-Weber-Rendu disease (Osler disease) associated with von Willebrand's disease (vW disease) type I. Previously, 28 Cases (8 families) with these two disease association have been reported. These disease seems to coexist as an inevitable consequence, because the disorder of vascular endothelial cells where von Willebrand factors are synthesized is a common pathogenetic factor in Osler disease. It is considered that such a case is secondary vW disease. Moreover, previous reports of Osler disease associated with various hemostatic defects are reviewed. PMID- 1942542 TI - [Tumor-forming type IgA (kappa) multiple myeloma developed into polyclonal hyper gamma-globulinemia after M-protein loss]. AB - A 77 year-old female admitted with costal and right clavicular tumors and multiple osteolytic lesions. In January 1983, a diagnosis of mature type plasmacytoma was made based on the histopathological examination of the right clavicular tumor. The amounts of serum protein and IgA (kappa) M-protein were 7.5 g/dl and 2.1 g/dl, respectively. A myelogram revealed 21% of mature plasma cells with 31.3 x 10(4) nucleated cells/microliter. Four months later following a chemotherapy started in March 1983, the tumor size became smaller with undetected M-protein by an immunofixation method. Besides, a serum protein analysis showed 24.6% of gamma-globulin and 1,980 mg/dl of IgG. However, in December 1983, the right clavicular and costal tumors regrew. The second biopsy specimen showed diffuse proliferated plasmablastoid cells which reacted only to anti-kappa antibody. By August 1984, the patient had systemic subcutaneous tumors as well as polyclonal IgG up to 3,356 mg/dl suggesting rapid progression of the disease. A myelogram showed 7.4% of mature plasma cells. In December 1984, the patient died of complicated obstructive ileus due to multiple mesenteric tumor. In this study we discussed on the role of M-protein loss and increased of normal globulin level in a tumor-forming type multiple myeloma. PMID- 1942543 TI - [Effectiveness of etoposide on reactive histiocytosis and refractory state to platelet transfusion during therapy of leukemia: case report]. AB - The patient is 11-year-old girl who was diagnosed as having hybrid acute leukemia (myeloid and lymphoid) from morphological (cytochemistry) findings, immunophenotype and genotype. During reinduction therapy after a second relapse, she presented hepatosplenomegaly and the remittent fever unresponsive to the intensified antibiotics. The diagnosis of reactive histiocytosis was made because of the remarkable elevation of serum ferritin value and proliferation of mature histiocytes in the bone marrow. Treatment with etoposide resulted in the disappearance of her fever and other symptoms. The subsequent refractoriness to platelet transfusion was also overcome by etoposide (p.o.) therapy. The results suggested that the treatment with etoposide might be effective for reactive histiocytosis and the related refractory state to platelet transfusion during therapy for leukemia. PMID- 1942544 TI - [Management of cesarean section under replacement therapy with factor VIII concentrates in a pregnant case with congenital combined deficiency of factor V and factor VIII]. AB - The congenital combined deficiency of Factor V and Factor VIII, a rare bleeding disorder, was identified in a 25-year-old woman. She was admitted to our hospital with a complaint of genital bleeding. Her prothrombin time and activated partial thromboplastin time were prolonged. She had low levels of Factor V coagulant activity (F. V:C) 14%, and Factor VIII coagulant activity (F. VIII:C), 12%, and normal levels of von Willebrand factor antigen (vWF:Ag), ristocetin cofactor (Rcof) and Protein C antigen. Her Protein C inhibitor level was slightly low. Her Rcof, vWF:Ag and F. VIII:C were elevated following administration of 1-deamino-8 D-arginine-vasopressin (DDAVP), but her F. V:C remained unchanged. Four years later, her F. VIII:C rose to 70% during the course of her pregnancy, but her F. V:C value remained low. It was expected that the vaginal delivery would be possible at the termination of pregnancy. Premature rupture of the membranes and an anomaly of rotation appeared in the course of delivery, however, and cesarean section was accomplished without excess bleeding under replacement therapy with Factor VIII concentrates. These findings suggested that DDAVP and Factor VIII concentrates were useful for management of her delivery. However the mechanisms of the rise of plasma F. VIII:C during pregnancy in a case with congenital combined deficiency of Factor V and Factor VIII are unclear. PMID- 1942545 TI - [Altered expression of protooncogenes during clinical course in an AML case transformed from MDS]. AB - The changes of expression of oncogenes in the mononuclear cells of MDS case was studied during his clinical course, in series. His bone marrow was considered to maintain its function partly in initial stage, since both peripheral blood and bone marrow responded to clinical episodes. However, his hematopoietic function was gradually impaired with the disease evolution to AML. We examined the expression of four oncogenes in the mononuclear cells of his three clinical stages, early RAEB-t, RAEB-t and AML, to study the cause of transformation from MDS to AML. Early RAEB-t cells expressed all oncogenes studied other than c-myb, while only c-myc was weakly observed in RAEB-t. AML cells expressed c-myc, c-jun and c-myb, except for c-fms. The expression of c-fms and c-jun of early RAEB-t was considered to reflect the monocytosis induced by infections, and the expressions of c-myb and c-myc of AML cells were regarded as one of malignant signs of tumor transformation. These findings suggest that the evolutional transformation of MDS to AML was affected by the altered expression of oncogenes. PMID- 1942546 TI - [Marked bone marrow necrosis preceding acute myeloblastic leukemia in childhood]. AB - A 3-year-old boy was transferred to our hospital because of fever, abdominal pain and severe systemic bone pain on October 16, 1989. Hematological examination showed hemoglobin 8.7 g/dl, white blood cell count 5300/microliters with 9% neutrophils and platelet count 5.5 x 10(4)/microliters. Bone marrow aspiration and biopsy revealed markedly necrotic cells. Blood chemistry showed transient elevation of CRP, serum LDH, FDP, FDP-Ddimer and fibrinogen. Tc99m pyrophosphate bone scanning showed multiple uptake spots in various bone. Although the sign of fever, abdominal pain and bone pain disappeared spontaneously after three weeks, anemia persisted. About two months later from bone marrow necrosis, abnormal cells appeared in the bone marrow. A diagnosis of AML (M3) was made and a combination chemotherapy started. This case is remarkable for elevation of acute phase protein in association with bone marrow necrosis. PMID- 1942547 TI - [Hypoplastic leukemia successfully treated with low-dose aclarubicin: a case report]. AB - Low-dose aclarubicin (LDACR) therapy is one of the differentiation induction therapy, such as low-dose cytosine arabinoside therapy, 1 alpha, 25 dihydroxy vitamin D3 or retinoic acid therapy, for myelodysplastic syndrome and atypical leukemias. A 36-year-old female with hypoplastic acute myelogenous leukemia was treated with this atypical leukemias. A 36-year-old female with hypoplastic acute myelogenous leukemia was treated with this LDACR therapy. On admission, she was suffered from general fatigue and her peripheral blood smear showed pancytopenia with 23% of myeloblasts. Bone marrow examination revealed a moderately hypoplastic marrow with 35.4% of myeloblasts. She was diagnosed as having hypoplastic acute myelogenous leukemia. Thereafter, 20 mg of aclarubicin was given daily by one-shot intravenous injection for 10 days. After this LDACR therapy, myeloblasts disappeared from her peripheral blood and pancytopenia improved. Bone marrow examination showed increase in nuclear cell counts and she achieved complete remission. In this article, we report the clinical course of this patient and discuss the effect of LDACR therapy as useful chemotherapy for this patient. PMID- 1942548 TI - Phase II evaluation of combined cisplatin and vindesine in advanced squamous cell carcinoma of the esophagus: Japanese Esophageal Oncology Group Trial. AB - In the present phase II study, 31 patients with advanced measurable esophageal carcinomas were treated with a combination of 30 mg vindesine/m2 and 70 mg cisplatin/m2. The overall response rate was 16.1% (95% confidence limits, 7.1 32.6%). Responses were seen in metastatic sites, including the liver in two patients, a lung in one, neck or mediastinal lymph nodes in two and primary sites in two. The response durations were between one and two months for patients achieving partial response. The average survival time after first administration was 5.5 months for patients who responded to treatment, whereas, for those who did not, it was 7.3 months. The major form of toxicity was myelosuppression, 14 patients developed grade 2-3 toxicity and one sepsis which led to death. No superiority of the combined chemotherapy over either cisplatin or vindesine therapy alone was suggested for cases of advanced squamous cell carcinoma of the esophagus by the present study. PMID- 1942549 TI - Effects of continuous vindesine administration of advanced breast cancer resistant to chemotherapy including adriamycin. AB - Vindesine (VDS) at a dose of 1.2 mg/m2/day was administered by intravenous drip infusion for five days to advanced breast cancer patients with multiple organ metastases who had developed a clinical resistance to various chemotherapeutic agents. The blood concentration of VDS was determined serially by radioimmunoassay, and the anticancer effect and side effects were evaluated. Of the 31 patients selected for this study, 29 were eligible, and the treatment was effective (complete or partial remission) in 11 (38%). There was, however, no correlation between clinical effects and VDS blood concentration. Continuous VDS administration induced various side effects, but all were controllable. Blood concentration was correlated with side effects. Continuous intravenous administration of VDS is considered to have a therapeutic effect on advanced breast cancer which has developed resistance to multiple-drug therapy including adriamycin. PMID- 1942550 TI - Triple carcinomas in Cronkhite-Canada syndrome. AB - The present report describes a 69-year-old man displaying the clinical features of the Cronkhite-Canada syndrome. After taking medicine for the common cold, he suffered hypogeusia and watery diarrhea, eruptions on the lower extremities and an 8 kg loss in body weight. All his finger and toenails began to fall out. He underwent an upper gastrointestinal examination, upon which multiple polyps of the stomach were detected. Three years later, he again developed diarrhea, bloody stools, body weight loss and eruptions on the lower extremities. An upper gastrointestinal series showed a diverticulum of the esophagus and multiple polyps in the stomach. A barium enema examination revealed polyps throughout the entire colon. Endoscopical biopsy specimens revealed juvenile type polyps and adenomas. The patient was treated with predonine therapy and, in a few days, his symptoms improved. Following the predonine therapy, an upper gastrointestinal endoscopy revealed superficial esophageal cancer and early gastric cancer. The patient received successful surgical treatment. Macroscopically, the esophageal cancer was of the superficial type, and its histologic type was that of moderately-differentiated squamous cell carcinoma. The gross finding on the stomach cancer was one of superficial depressed type, and its histologic type was that of well-differentiated tubular adenocarcinoma. One year later, lung cancer was detected. The gross appearance of the resected lung tumor was one of a grayish-white color and the neoplasm was histologically diagnosed as undifferentiated carcinoma, small and large cell type. The coexistence of carcinoma of the gastrointestinal tract with Cronkhite-Canada syndrome has been reported in 21 cases. We have found no report, however, of lung cancer associated with Cronkhite-Canada syndrome. The case described herein is, therefore, the first case of Cronkhite-Canada syndrome to be associated with esophageal, gastric and lung cancer. PMID- 1942551 TI - Neuroendocrine carcinoma of the urinary bladder: case report and review of the literature. AB - A 63-year-old Japanese man complained of hematuria and pollakisuria for several months. Computed tomography and cystography disclosed an infiltrative tumor mass in the irregularly thickened apical and posterior walls of the urinary bladder. Narrowing of the vesical lumen and posterior extension of the tumor into the pelvic cavity were also noted. After palliative ureterocutaneostomy, 60 Gy irradiation was given locally. The patient died of cachexia seven months later. Autopsy revealed neuroendocrine carcinoma of the urinary bladder with extensive invasions and metastases to the pelvic and peritoneal cavities, liver, lungs, vertebrae, left kidney and retroperitoneal lymph nodes. Histologically, atypical tumor cells with eosinophilic cytoplasm formed solid nests and anastomosing cords with pseudoglandular structures. No other histologic tumor components were included. An intact urachal remnant was found at the vesical apex while features of metaplastic cystitis were absent. In addition to positive carcinoembryonic antigen and cytokeratin, the argyrophilic cancer cells were immunoreactive for neuron-specific enolase, chromogranin A, serotonin, neuropeptide Y, glicentin, somatostatin, neurotensin and calcitonin. Ultrastructurally, neurosecretory-type granules, with a mean diameter of 166 nm, were identified in the cytoplasm of the tumor cells. To discuss the histogenesis of the tumor, 44 previously reported cases of neuroendocrine carcinoma of the urinary bladder were reviewed. PMID- 1942552 TI - Esophageal and pulmonary metastases from ovarian carcinoma: a case report of long term survival following metastatic resections. AB - A case of ovarian carcinoma which has been followed up for more than 28 years after the initial ovarian resection is reported. A 50-year-old woman came forward with a metastatic esophageal tumor 16 years after a salpingo-oophorectomy for ovarian carcinoma. After irradiation with a dose of 3090 cGy, an esophagectomy and a partial resection of the directly invaded pericardium was successfully performed. Ten years later, progressive dyspnea due to a total collapse of the right lung developed. The right main stem bronchus was almost occluded by an endobronchial tumor, contiguous with the recurrent mass at the previous resectional margin. A right pneumonectomy and a combined resection of the pericardium and left atrium were performed. The patient has been followed up for further two years, and no signs of recurrence are evident. In spite of distant thoracic involvement and its local regrowth, the patient has survived for 28 years following her initial resection with surgical interventions. PMID- 1942553 TI - Oncogenic vitamin D resistant hypophosphatemic osteomalacia (benign ossifying mesenchymal tumor of bone): case report. AB - A 53-year-old Japanese woman suffered hypophosphatemic osteomalacia secondary to bone tumor. Her clinical symptoms did not improve for a long time following the oral administration of Alfacalcidol (vitamin D3). A bone survey using radiographs revealed a small tumor located in the proximal head of the left fibula. Hypophosphatemia and low levels of 1-alpha,25-dihydroxycholecalciferol (1 alpha,25(OH)2D3) returned towards normal levels soon after an en-bloc tumor resection, and bone pain and muscle weakness gradually disappeared. The histology, especially of the trabecular bone of the left fibula, showed typical features of osteomalacia with demineralization. The tumor comprised numerous small blood vessels, spindle shaped or oval neoplastic cells, a few multinucleated giant cells, osteoid tissue with or without calcification, chondroid tissue and hemangioma. The spindle shaped or oval cells contained a round nucleus with no mitotic figures. These clinical and histological findings coincide well with a diagnosis of benign ossifying mesenchymal tumor of the bone with vitamin D resistant hypophosphatemic osteomalacia. PMID- 1942554 TI - Undifferentiated sarcoma of the liver in a 21-year-old woman: case report. AB - A successful surgical case of malignant undifferentiated (embryonal) sarcoma of the liver (USL), a rare tumor normally found in children, is reported. The patient was a 21-year-old woman, complaining of epigastric pain and abdominal fullness. Chemical analyses of the blood and urine and complete blood counts revealed no significant changes, and serum alpha-fetoprotein levels were within normal limits. A physical examination demonstrated a film, slightly tender lesion at the liver's edge palpable 10 cm below the xiphoid process. CT scan and ultrasonography showed an oval mass, confined to the left lobe of the liver, which proved to be hypovascular on angiography. At laparotomy, a large, 18 x 15 x 13 cm tumor, found in the left hepatic lobe was resected. The lesion was dark red in color, encapsulated, smooth surfaced and of an elastic firm consistency. No metastasis was apparent. Histological examination resulted in a diagnosis of undifferentiated sarcoma of the liver. Three courses of adjuvant chemotherapy, including adriamycin, cis-diaminodichloroplatinum, vincristine and dacarbazine were administered following the surgery with no serious adverse effects. The patient remains well with no evidence of recurrence 12 months after her operation. PMID- 1942555 TI - Occurrence of multiple primary cancer at the National Cancer Center Hospital, 1962-1989. PMID- 1942556 TI - Lymphoproliferative diseases of the lung in Japan: review of thirty-six patients with an immunohistochemical study. AB - Thirty-six cases of primary lymphoproliferative disease of the lung, collected from hospitals in Japan, have been reviewed. Histologically they were divided into three groups: definite lymphoma (DL) showing monomorphous proliferation of medium to large cells (17 cases), small lymphoid cell proliferation (SLP) frequently containing lymphoid follicles (11 cases), and pseudolymphoma showing lymphoid follicular hyperplasia (LFH) (six cases) or mixed diffuse infiltration of small lymphocytes and macrophages (two cases). In some DL cases, lymphoid follicles were present in or near the tumors. Pulmonary lesions in SLP and LFH patients were frequently detected at their medical checkups. Immunohistochemistry revealed that proliferating cells in 15 out of 17 DL and all SLP cases were B cells with restricted expression of the immunoglobulin light chain, all lambda type, in three DL and four SLP cases. From morphologic and immunologic findings, 10 SLP cases were diagnosed as intermediate lymphocytic lymphoma (ILL) and one as being of lymphoplasmacytic type. Two DL cases with convoluted nuclei proved from immunohistochemistry to be of T-cell type, showing a much lower frequency of T cell type than that found in the USA (approximately 50%). PMID- 1942557 TI - Studies by pancreatography of ductal changes induced by administration of pancreatic carcinogen in two dogs. AB - To assess the temporal changes of the pancreatic duct following the administration of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in two dogs, serial pancreatography was performed. They received intraductal administration of a total of 595 and 500 mg ENNG in each one, over the periods of 12 and 13.5 months, respectively. In one dog, sequential changes of the main duct were observed, a small round filling defect developed a circumferential defect and became a severe stenosis associated with proximal dilatation of the duct. While no gross tumors were macroscopically detected at autopsy, continuous lesions with features of hyperplasia, atypical hyperplasia, and cancerous change of duct epithelial cells were microscopically seen. In the other one, a small round filling defect was detected by pancreatography, which was histopathologically hyperplasia of pancreatic duct, rather than cancerous cells. The present dog model for induction of pancreatic duct carcinomas appears useful for elucidating clinico-pathological changes occurring during cancer development. PMID- 1942558 TI - Treatment of myelodysplastic syndromes with orally administered N-(2S, 3R)-3 amino-2-hydroxy-4-phenylbutyryl-L-leucine (ubenimex). AB - N-(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine (ubenimex) was administered orally, to patients with myelodysplastic syndromes (MDS) and acute leukemia derived from MDS, in a multi-institute study. Out of 77 patients evaluated, one achieved a complete remission, three a good response and two a partial response while 71 failed to respond to a daily oral administration of 30 mg ubenimex. The overall response rate was 7.8% (95% confidence limits; 3.6 16.0%); 7.0% (3.0-15.4%) in 71 MDS and 16.6% (3.0-56.3%) in acute six leukemias derived from MDS. Responses continued for six to 24 (median 10.5) weeks. No serious hematologic, biochemical or clinical toxicity was encountered, except for gastro-intestinal (GI) toxicity in one patient. The present study demonstrated ubenimex not to be generally beneficial for patients with MDS, and not to be recommended as a standard treatment for the disease. PMID- 1942559 TI - A long-term survivor of metastatic gastric cancer treated by chemotherapy: case report. AB - A long-term survivor of advanced gastric cancer with multiple metastases to the liver treated by chemotherapy is described. Chemotherapy comprising a combination of uracil and tegafur with mitomycin C achieved a complete response in the patient which lasted for approximately four years. Four years after initiation of the chemotherapy, a unique form of cancer recurrence occurred on the skin, showing infiltrative erythema. Cancer metastases developed further despite more treatment, and the patient died of generalized metastasis four years six months after the initiation of chemotherapy. It is significant that, at autopsy, no cancer cells were revealed in the primary lesion or in the liver which had been present before the initial chemotherapy. PMID- 1942560 TI - Primary malignant melanoma of the esophagus: report of four cases. AB - We report four cases of malignant melanoma of the esophagus treated at the National Cancer Center Hospital in Tokyo over a period of 28 years. There were three men and one woman. One patient had been diagnosed as having Werner's syndrome. The three male patients smoked and were alcohol drinkers. The chief complaint was dysphagia--three patients--and pain on swallowing--one patient. All the tumors were polypoid, and three were large at the time of initial diagnosis. Histological diagnoses were made by examining endoscopic biopsy specimens, and confirmed with resected specimens in three cases. Esophagectomy was performed in three patients, the other receiving radiotherapy. Three patients died of recurrent disease in a rather short period of time, as in many reported cases. The mean survival for the three patients was eight months. The fourth, who had a superficial polypoid lesion and received esophagectomy and adjuvant chemotherapy, lived for 29 months. The combination of early detection and extended radical surgery followed by adjuvant chemotherapy may offer a better prognosis than in the past. PMID- 1942562 TI - Cancer incidence and incidence rates in Japan in 1986: estimates based on data from nine population-based cancer registries. The Research Group for Population based Cancer Registration in Japan. PMID- 1942561 TI - A case of mixed lineage acute non-lymphocytic leukemia with t(5;12)(p13;p13). AB - A two-year-old boy had mixed lineage acute non-lymphocytic leukemia (ANLL) with a 46,XY, t(5;12)(p13;p13) karyotype. He was admitted to the hospital with fever and petechiae. Morphological and cytochemical characteristics showed the blasts to meet the standard French-American-British criteria for M1, but surface marker analysis showed the blasts to express both myeloid (CD33: 91.3%) and T-cell (CD2: 82.3%, CD7: 97.9%) antigens. The boy was treated with an ANLL protocol, and successfully brought to a remission which has continued for more than 30 months. PMID- 1942563 TI - [Clinical assessment of posterior pituitary function by measurement of unextracted random urine]. AB - To evaluate posterior pituitary function without any provocative examination, vasopressin (AVP) concentrations of random urine were measured by high-sensitive radioimmunoassay (AVP-RIA Kit, Mitsubishi Petrochemical Co., Ltd.). No apparent interference for the AVP measurement in unextracted urine was seen after appropriate dilution of urine sample. Urinary AVP did not degenerate at least for 24 hr at room temperature. AVP concentration of random urine was significantly correlated with AVP excretion in 24hr-urine in normal subjects. In 25 patients with neurogenic diabetes insipidus diagnosed by hypertonic saline infusion test, the AVP concentration in random urine was less than 13 pg/mg Cr. In approximately 1% of the normal subjects the urinary AVP level was below this range. Therefore, more intensive examinations should be planned to rule out the failure of AVP secretion in the case of such low AVP level in random urine. We also investigated the physiological changes in AVP secretion in 815 children and 352 pregnant women by measurement of urinary AVP. Even a large number of samples could be measured using this simple procedure. PMID- 1942564 TI - [Recent developments of measurements for pituitary-thyroid hormones: evaluation of five immunometric assay methods (RI and non RI methods]. AB - We evaluated five commercially available immunoassay kits for pituitary-thyroid function tests. The possible interference in analysis by immunoglobulin G (IgG) has also been examined. The BeriLux TSH assay kit (Hoechst co. FRG) was compared with two other non-RI methods (AIA-1200 and IMx) and two other immunoradiometric assays (RIA-gnost TSH IRMA and EIKEN IRMA kits) in 32 normal subjects and 92 patients with Graves' disease. The new ICMA BeriLux kit had a marked improved analytical and clinical sensitivity. The minimal detectable level of TSH in the assay was 0.006 mU/l. The precision was 2.8% and 6.1% at 0.093 +/- 0.003 mU/l and 0.028 +/- 0.002 mU/l, respectively, whereas the levels for the other methods were above 17.2% and 59.4% respectively. The TSH pattern was always less than 0.006 mU/l with the BeriLux kit, before and after TRH administration whereas the other methods showed random fluctuations which indicated their low accuracy at this concentration. This new ICMA BeriLux kit appears far more reliable than the ordinary immunometric assay kits. PMID- 1942565 TI - [Evaluation of immunological tests in thyroid diseases]. AB - We evaluated immunological tests for autoimmune thyroid diseases. Although both humoral and cellular immunity are correlated to the onset and pathophysiological progression of these diseases, the major tests employed in daily clinic belong to the former. We measured the anti-TSH receptor antibody (TRAb, TBII), circulating immune complex (CIC), thyroid growth stimulating immunoglobulin (TGSI) and interleukin-2 (IL2) levels in patients with Graves' disease (GD) and chronic thyroiditis (CT). The normal range of TRAb in 190 healthy controls was from -10.9 to +10.3% calculated from the mean +/- 2SD. Sixty eight out of 78 untreated cases of GD (87.2%) showed a higher TRAb than the upper normal level (positive), 92 out of 131 cases of GD under treatment (70.2%) were positive and only 5 out of 57 cases of treated GD (8.8%) were positive. Three neonates out of 12 GD mothers had a positive TRAb and one of them developed neonatal GD. Nine out of the 45 CT (20%) had positive TRAb, but about half were euthyroid and goitrous. In untreated GD, CIC was distributed widely from the normal range to high levels. CIC showed a significantly negative correlation with TRAb. TGSI correlated with goiter size and CIC in GD revealed autologous inhibition on TGSI. Three cases showed markedly decreased levels of TRAb which was found to be due to anti-TSH antibodies. Production of IL2 in GD was impaired, but it was improved by treatment of GD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942566 TI - [Thyroid dysfunction and histologic correlation using thyroid needle biopsy specimens]. AB - In this article, we describe the usefulness of thyroid needle biopsy in the differential diagnosis of thyroid disorders revealing unusual thyroid function. Firstly, we describe the relationship between thyroid function and its histology in 601 cases of chronic thyroiditis. In the histologic group A, the majority of the cases showed a latent or overt hypothyroidism and in histologic group B, hyperthyroid, euthyroid and latent hypothyroid cases were found in nearly equal frequency, respectively. In histologic group C, most cases were in euthyroid and in histologic group D, most cases showed a hyperthyroidism. In the silent thyroiditis and postpartum thyroiditis, known to show a characteristic clinical and laboratory finding, the histologic features of thyroid gland were as follows: the observed characteristic histologic changes in both diseases were an extensive follicular destruction associated with chronic diffuse thyroiditis. These destructive changes disappeared in association with the clinical and laboratory recovery. In the patients with iodine-excess hypothyroidism, the thyroid glands also revealed characteristic histologic changes. A marked hyperplastic change of follicular cells and a lack of colloid material in the follicular lumen was the predominant histologic feature. Based on our personal experiences, thyroid needle biopsy should be recommended as a useful tool for differentiation of causes of hyper- or hypothyroidism. PMID- 1942567 TI - [Bone mass and biochemical parameters in metabolic bone diseases]. AB - We studied the relationship between the bone mass and biochemical parameters in 175 normal premenopausal, 72 normal postmenopausal and osteoporotic postmenopausal women, between 20 and 88 years old, and in 40 patients with hyperthyroidism, and 23 patients with primary hyperparathyroidism, between 13 and 64 years old. The bone mineral density (BMD) of the spine (L2-L4) and proximal femur (femoral neck) was measured by dual-energy X-ray absorptiometry using a QDR 1000, Hologic. The bone mineral content (BMC) of the radius was measured by single photon absorptiometry (SPA) using a model 2780, Norland. Serum PTH, BGP and calcitonin (CT) were determined by radioimmunoassay. The BMD of the spine (L2 L4), and the proximal femur in postmenopausal women were negatively correlated with age. The mean BMD in patients with postmenopausal osteoporosis was significantly lower than that in normal postmenopausal women. In postmenopausal women, age was positively correlated with BGP, PTH, CT and negatively correlated with P. In patients with osteoporosis, the BMD of the spine was negatively correlated with serum BGP. The BMC of radius in patients with hyperthyroidism decreased significantly compared with that in the controls, and was negatively correlated with F-T3. The BMC of the radius in patients with primary hyperparathyroidism was significantly lower than that in the controls, and was negatively correlated with serum BGP and serum calcium. The measurements of biochemical parameters such as serum BGP, ALP and PTH may be useful in the assessment of metabolic bone diseases. PMID- 1942568 TI - [Diagnosis of adrenal diseases focusing on morphological and endocrinological viewpoints]. AB - The recent advances in the diagnosis of adrenal diseases owe much to the rapid progress in radiological and endocrinological areas. The former is ascribed to the progress of medical electronics. The latter has been realized by the development, improvement and spread of the measurement of a very small amount of hormones or hormone-like substances in blood, urine or tissues, supported by the improvement of measurement instruments as well as the immunoassay or chemical assay techniques. This paper reviews approaches to diagnosis of adrenal diseases causing hypertension and asymptomatic, incidentally discovered adrenal tumors. Incidentally discovered adrenal tumors have increased owing to the spread of medical electronic instruments such as abdominal ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). Discrimination of malignancy is an important clinical concern. More than 90% of the tumors reported in the Japanese were larger than 3 cm in diameter. The diagnosis of primary aldosteronism has been made by the measurement of plasma renin and aldosterone, CT and 131I-cholesterol scintigraphy. However the differential diagnosis of adrenal adenoma from bilateral adrenal hyperplasia has remained as a problem. There were a few patients in whom adrenal adenomas appeared after 2-3 years' follow-up period. In Cushing's syndrome, tumors are found with ease by US, CT and MRI. The diagnosis of pheochromocytoma is made mainly by urinary catecholamines and metabolites including metanephrine, normetanephrine and VMA. US, CT and MRI are very useful. Diagnosis and discovery of metastasis will be more reliably made when 131I-MIBG comes to the clinical stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942569 TI - [HIV infection of CD4-CD8+ T-cell line derived from patients with HAM]. AB - This studies have attempted human immunodeficiency virus (HIV) infection in four CD4+ or CD8+ T-cell lines derived from HTLV-I associated myelopathy virus (HAM) patients. Not only CD4+ cell line but also CD8+ cell line could be infected with HIV and CD4+ cell line showed a higher susceptibility than CD8+ cell line on HIV infection. HIV antigen in early stage after HIV inoculation was detected by using enzyme-linked immunosorbent assay (ELISA) rather than indirect immunofluorescence assay (IFA). HTLV-I producing CD4+ and CD8+ cell lines became to express two viral antigens (HTLV-I and HIV) after HIV inoculation. The results indicated that CD4-CD8+ T-cell line from patient with HAM can be infected with HIV. So that, we have found that other epitopes except for CD4 antigen may be associated with HIV infection. PMID- 1942570 TI - [Detection of immature granulocytes and atypical and/or abnormal lymphocytes using scatterplots of Coulter STKS]. AB - Scatterplots of the Coulter STKS were studied in order to make better analyses of morphological abnormality of leukocytes. The analytical pattern of a sample failed to completely prevent blood coagulation, especially platelet aggregation, showed the poor separation between lymphocyte and neutrophil populations. On the scatterplot, a small population was occasionally observed in the lower area of normal lymphocyte population with elevation of room temperature, being thought an artificial population. When atypical and/or abnormal lymphocytes increased, the pattern was characterized by the distribution of large lymphoid cells spreading over monocyte population area. The characteristics became clear in proportion to the percentage of large lymphoid cells. To detect immature granulocytes, we introduced a criterion originated in our laboratory. Using the detection criterion, we could obtain the satisfactory results with sensitivity of 85%, specificity of 93%, efficiency of 91% and coefficient correlation (r) of 0.73. It is concluded that the pattern analysis and the detection criterion are useful in the experiments using routine laboratory samples and valuable in clinical implication. PMID- 1942571 TI - [An evaluation of automated hematology analyzers in detecting abnormal blood cells]. AB - We report the usefulness and capability of two hematology analyzers with different principles in characterization of abnormal cells such as immature granulocytes and blasts. We studied a total 1635 specimens which included 69 cases with hematopoietic malignancies. THMS H-1 (Technicon Instruments) and NE 8000 (Toa Instruments) were used as analyzers. An effort was made to determine the sensitivity and specificity of positive abnormal cell flag in comparison with the presence of abnormal cells seen on a manual differential. True positive rate for immature granulocytes in H-1 and NE were 43% and 30%, respectively. False positive rate for immature granulocytes in H-1 and NE were 0.01% and 0.03%, respectively. With both analysers, cases with low percentage of immature granulocytes generated negative flag for abnormal cells. True positive rate for blasts in H-1 and NE were 74% and 65%, respectively. False positive rate for blasts in H-1 and NE were 1.8% and 0.2%, respectively. With both instruments, in all cases with blast count over 100/microliters, blasts were detected. Only H-1 detected the cases with blast counts less than 100/microliters. In H-1 all cases with ATL, one case with AMMoL and another with ALL generated negative blast flag. Upon morphologic examination, these blasts were found to be large and peroxidase negative with convoluted and irregularly shaped nuclei. On the other hand, NE detected blasts regardless of those morphology. In conclusion, Both instruments are useful in screening abnormal blood cells, while their unique capability must be considered. PMID- 1942572 TI - [Histopathological study on fat necrosis with comparison between agonal stage and acute pancreatitis]. AB - A histopathological study on fat necrosis with a comparison between patients in agonal stage and those with acute pancreatitis was presented. Fat necrosis was observed in 15 out of 56 autopsied cases (26.8%) which were selected randomly from the autopsy file. Fat necrosis was frequently stained blue or purple with Nile blue stain, suggestive of acid lipid. The necrosis was usually accompanied by fibrin thrombi in the capillaries and reparative foam cells, nor hemorrhage and hemosiderin deposition. In acute pancreatitis fat necrosis also reacted blue or purple with Nile blue stain in 8 out of 9 patients. Reparative reaction was composed of granulation tissue in 6 patients, frequently with organized thrombosis in the veins. Fat necrosis was accompanied by fibrin thrombi and either hemorrhage or hemosiderin deposition. Therefore, differences in both hemorrhage or hemosiderin deposition and reparative change were observed in fat necrosis between patients in agonal stage and those with acute pancreatitis. PMID- 1942573 TI - [Measurement of enzyme activity of control materials containing human enzymes by IFCC reference methods]. AB - In order to unify interlaboratory clinical enzyme data, a reference method and reference material are necessary for each enzyme. Although reference methods recommended by various societies of clinical chemistry including JSCC are now available for some routinely measured clinical enzymes, the availability of secondary enzyme references or calibrators, limits the practical application of standardization concept for minimizing present interlaboratory variation of enzyme data. Since control sera prepared by adding enzymes from human cell cultures to a pool of human serum may meet the requirements as candidates for such reference materials, we attempted to assign values to 6 enzymes present in the materials by mainly the IFCC reference methods following the procedures as strictly as possible and yet with modifications where necessary. This paper describes each step of the value assignment for accuracy control purposes. PMID- 1942574 TI - [Time course study on the stability of the electrode in the oxygen consumption analyzer RM-200]. AB - We investigated the stability of the polarographic electrode, the CO2 electrode and the expired minute ventilation value (VE value) in the oxygen consumption analyzer RM-200 over a 6-month duration. A total of analyses 363 were performed on 71 normal subjects. Two methods were used; one is the gas response curve which directly shows the property of the polarographic electrode and the CO2 electrode, and the other is the Douglas bag method which is considered to be a standard method of O2 consumption (VO2) and CO2 output (VCO2) measurement. The gas response curve analyses were performed just after setting a new polarographic electrode, at the third month and at the sixth month. Measurement by the Douglas bag method was usually done once a week. The effects of respiratory rate on the values of VE, VO2 and VCO2 were evaluated from the ratio of each value measured by RM-200 to that obtained by the Douglas bag method. Evaluation by the gas response curve, revealed that the polarographic electrode was stable for 3 months, but not at the six month. The Douglas bag method revealed that a decrease in VO2 value had already occurred after a 4-month use of the polarographic electrode. However, a definite correction of the time constant allowed the use of the electrode up to six months. The VCO2 value and the VE value were stable for 6 months. Increase in the respiratory rate caused a slight but significant difference between VO2 and VCO2 values measured by RM-200 and those obtained by the Douglas bag method, but did not influence the VE values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942576 TI - [Molecular epidemiological study of molluscum contagiosum]. AB - The agarose gel electrophoretic analysis of molluscum contagiosum virus (MCV) DNA obtained from 92 Japanese patients revealed the presence of four different BamHI cleavage patterns of MCV DNAs, classified as MCV-1,2,3 and 4. MCV-1 was found in 69% of the patients, MCV-2 in 4%, MCV-3 in 25%, and MCV-4 in 2%. Almost all the isolates from children and all female adult cases were infected with either MCV-1 or 3. No obvious clinical differences were seen between these two types. MCV-4 was found in only two adult male cases. The sizes of the lesions induced by MCV-4 appeared to be larger than those of other types. Six sets of siblings were shown to be infected with the same types, whereas two sets were infected with the different types. Some different MCV types were found in the cases attending the same swimming pools. PMID- 1942575 TI - [Electrophysiological comparison between patients with Binswanger's encephalopathy and Alzheimer's disease]. AB - Short-latency somatosensory (SSEPs), brainstem auditory evoked potentials (BAEPs) and event-related potentials (ERPs) were studied in 7 patients with Binswanger's encephalopathy, 12 patients with Alzheimer's disease and 17 normal subjects. Patients with Binswanger's encephalopathy showed significantly prolonged central conduction time (CCT) and P300 latency, and prolonged tendency of I-V IPL compared to those of normal subjects. In particular, CCT showed significant prolongation compared to that of patients with Alzheimer's disease. In patients with Alzheimer's disease, I-V IPL and P300 latency were significantly prolonged compared to those of normals although there was no significant difference in CCT between Alzheimer's disease and normal subjects. These results indicate some difference between Binswanger's encephalopathy and Alzheimer's disease from the electrophysiological aspects although both of these entities are characterized by progressive mental deterioration. PMID- 1942577 TI - [Analysis of DNA synthetic activity of aged epidermis]. AB - The basal cells of old and young guinea pigs were separated by use of density gradient centrifugation. DNA contents of basal cells were measured on the smear specimens prepared by Feulgen's stainings. DNA synthetic activities of old guinea pigs and those of young guinea pigs were almost the same. These date suggested that there was no specific relationship between the DNA synthetic activity and aging of epidermis. PMID- 1942578 TI - [A flow cytometric study of the DNA content from paraffin-embedded samples of keratoacanthoma and squamous cell carcinoma]. AB - DNA-flow cytometry was performed on paraffin-embedded tissues from 7 cases of keratoacanthoma (KA) and squamous cell carcinoma (SCC). Proliferation index of tumor cells (% greater than 4SD) was defined as the percentage of cells that exceeded the diploid peak (G0G1) plus 4 standard deviations (SD). Proliferation index (% greater than 4SD) was lower than 20% in six out of 7 cases of KA, but higher than 25% in six out of 7 cases of SCC. One case of SCC showed a DNA aneuploidy. These results indicate that DNA-flow cytometry analysis using paraffin-embedded tissues may be a useful tool in differential diagnosis between keratoacanthoma and squamous cell carcinoma. PMID- 1942579 TI - [Electron microscopic study of the human adult intraepidermal eccrine sweat duct- the formation of the intracytoplasmic cavity]. AB - The human adult intraepidermal eccrine sweat duct (IESD) were studied by the transmission electron microscope. The formation of the intracytoplasmic cavities was demonstrated in the luminal cell of the adult IESD, and the relation between the intracytoplasmic cavities and the IESD formation was as follows. On the eccrine sweat duct ridge, these intracytoplasmic cavities enlarged, broke through the cell membrane and coalesced into the intercellular lumen. Furthermore, several intercellular lumina were merged into the intraepidermal ductal lumen. In the lower to upper squamous layers, small intracytoplasmic cavities were formed around the intraepidermal duct and were fused into the duct. Simultaneously, the contents of the intracytoplasmic cavities were discharged into the ductal lumen. Intracytoplasmic cavities in these layers were ordinarily formed and concerned in not only the reconstruction of the duct but also the secretory function. The intracytoplasmic cavities were surrounded with the same microvilli as lined the intraepidermal ductal lumen. Many clear vesicles (about 0.1 microns in diameter) were observed near the intracytoplasmic cavities, but multivesicular dense bodies (MDB) were not seen near the cavities. These vesicles were considered to participate in the formation of the intracytoplasmic cavities. PMID- 1942580 TI - [A dramatic effect of continuous intra-arterial injected recombinant interleukin 2 immunotherapy on malignant hemangioendothelioma]. AB - A malignant hemangioendothelioma (MHE) developed on the frontal scalp of an 83 year-old woman was treated with intralesional injection of recombinant interleukin-2 (rIL-2, TGP-3, Takeda Chemical Industries LTD, Osaka) which had lead the lesion to complete remission for 2 years and 9 months. After the period of the complete remission, the patient developed MHE lesion on the occipital scalp which rapidly enlarged to more than 10 cm in diameter within 7 days, though there was no recurrence of MHE on the frontal scalp at that time. Intra-arterial rIL-2 injection was conducted through the occipital artery which circulates around the tumor lesion, but resulted unsuccessful because of the obstruction of the artery. Continuous intra-arterial rIL-2 injection through bilateral superficial temporal arteries was conducted, and then the tumor lesion came to complete remission on both clinical and histological data. So far, the patient has been showing no local recurrence or metastasis for the period of 8 months. We conclude that continuous intra-arterial rIL-2 injection immunotherapy through superficial temporal arteries is the best way of all the treatment in cases with recurrent MHE located on occipital scalp. PMID- 1942581 TI - [Neurilemmomatosis--a sporadic and familial cases]. AB - Three cases of neurilemmomatosis are reported. A 22-year-old man without any relatives with similar symptoms visited our clinic, complaining of multiple skin tumors since the age of 15 and bilateral acoustic nerve symptoms since 19. Physical examination revealed no pigmented or depigmented spots. Histopathological examination of the eight tumors excised from the skin, acoustic nerve and spinal cord showed that these were all neurilemmomas. A 36-year-old man with a 15 year history of multiple skin tumors and one year history of acoustic nerve symptoms was seen at our clinic, revealing no pigmentary disorders. The tumors excised from the skin and bilateral acoustic nerves were all neurilemmomas histopathologically. A 5-year-old boy, who was the only child of the second case and had had several skin tumors since his birth, visited us after postoperative death of his father. He revealed no pigmentary abnormalities. The histology of the skin tumor was neurilemmoma. The absence of neurofibromas and pigmented spots in these patients with neurilemmomatosis suggests that this disorder might be close to, but distinct from neurofibromatosis. Although familial cases of neurilemmomatosis like our case 2 and 3 reported so far are very few, they support a possibility that neurilemmomatosis might be a genetically determined neurocutaneous syndrome, a kind of phacomatosis. PMID- 1942582 TI - [Solitary reticulohistiocytic granuloma--a report of three cases and a review of literature]. AB - Case 1 was a 20-year-old male with a nodule on the scrotum. Case 2 was a 14-year old female with a dome-shaped, reddish-brown nodule on the nose. Case 3 was a 30 year-old male with a dome-shaped, reddish-brown nodule on the forearm. All of the excised specimens showed typical features of solitary reticulohistiocytic granuloma. There were histiocytes and multi-nucleated giant cells in the dermal tumorous nests. They were stained positively with PAS reaction and anti-lysozyme antibody, but were stained negatively with S-100 protein antibody. To clarify the nosology of the reticulohistiocytic granuloma, we reviewed the literatures of multicentric reticulohistiocytosis and adult xanthogranuloma. Multicentric reticulohistiocytosis was considered to be a systemic disease and different from solitary reticulohistiocytic granuloma. However, adult xanthogranuloma showed clinical similarities to solitary reticulohistiocytic granuloma instead of the differences in the histopathologic features. PMID- 1942583 TI - [Polymerase chain reaction for the diagnosis of tsutsugamushi disease]. AB - A polymerase chain reaction (PCR) using specific oligonucleotide primers and Taq polymerase was developed for the detection of Rickettsia tsutsugamushi, the causative agent of tsutsugamushi disease. Oligonucleotide primers were synthesized on the basis of DNA sequences encoding 58 kD antigen of R. tsutsugamushi. Specific DNA amplification of 358 bp and 109 bp DNA fragments were demonstrated using patient's blood. This PCR method would enable to make a rapid and sensitive diagnosis of tsutsugamushi disease. PMID- 1942584 TI - [The influence of ursodesoxycholic acid (URSO) on griseofulvin (GF)-induced protoporphyria]. AB - To investigate the influence of ursodesoxycholic acid (URSO) on griseofulvin (GF) induced protoporphyria mice, analysis of hepatic, erythrocytic, and fecal porphyrin levels and histopathological examinations were performed in dd-Y strain mice treated with 0.5% GF and/or 0.5% URSO. We observed no difference of hepatic and fecal porphyrin levels between the GF group and GF with URSO group, although an elevation of erythrocytic porphyrin levels was seen in the GF with URSO group. However, remarkable hepatic atrophy revealed in the GF with URSO group. Furthermore, a strong emission of red fluorescence was observed in the liver under long wave ultraviolet. Histopathologically, many focal necrosis was found in the liver specimen treated with GF and URSO. We expected that URSO might facilitate the excretion of porphyrin from bile to feces because of suppression of transfer from serum to erythrocyte like cholic acid (CA). But, the action of URSO appears to be different from that of CA. We consider that the 0.5% concentration of URSO plays a role in the cytotoxic effect to the liver. PMID- 1942585 TI - [Type IV collagen and laminin levels in the sera from patients with systemic scleroderma (PSS)]. AB - Serum type IV collagen 7S and laminin P1 levels were measured with radioimmunoassay in 33 patients with systemic scleroderma (PSS), 6 localized scleroderma (LS), and one mixed connective tissue disease (MCTD). Serum type IV collagen 7S levels were higher in PSS (5.11 +/- 1.11 ng/ml:m +/- SD) and LS (4.68 +/- 0.46 ng/ml) than in normal controls (3.90 +/- 0.85 ng/ml) (p less than 0.001). Serum laminin P1 levels were also significantly higher in PSS (1.75 +/- 0.34 U/ml) and LS (1.38 +/- 0.20 U/ml) compared to the controls (1.19 +/- 0.16 U/ml) (p less than 0.001 and p less than 0.01, respectively). A significant correlation between these two values in PSS was found (r = 0.465, p less than 0.02). These results suggest that the measurements of these values may serve as a marker of PSS. PMID- 1942586 TI - [Juvenile dermatomyositis--statistical observation of 105 patients with dermatomyositis]. AB - Statistical observation about the clinical items of 105 patients with dermatomyositis (DMS) attending Department of Dermatology, Nagoya University Hospital and some hospitals in Aichi Prefecture, during the year of 1965 to 1989, was carried out. Clinical features of the patients with juvenile DMS obtained from the observation were as follows. 1) The male:female ratio was 1.3:1 in juvenile DMS. The evident difference such as the predominance of females in adult DMS was not found. 2) The tendency that cutaneous manifestations usually preceded muscular manifestations was observed, and the muscular manifestations except severe symptoms were seen with a high incidence throughout the entire clinical course. 3) In the laboratory examinations, the incidence of elevation of serum aldolase concentrations in children was significantly higher than that in adults (p less than 0.05). Serum aldolase concentrations were usually elevated at onset or prior to the onset of muscular manifestations. Therefore the measurement of serum aldolase levels was considered to be useful for early diagnosis of juvenile DMS. The positive rate of antinuclear antibody in children was significantly lower than that in adults (p less than 0.001). 4) None of the children had any complications such as malignant tumors, interstitial pneumonia and pulmonary fibrosis, and none of them died. With regard to the outcome, the incidence of "remission or improvement" in children was significantly higher than that in adults (p less than 0.05). In the group of "same or worse", the children mainly had the cutaneous manifestations which were difficult to treat, compared with the adults. These results suggest that juvenile DMS may be a different disorder, probably a syndrome, from adult DMS. PMID- 1942587 TI - [Statistical observations of pemphigus at the Nara University Hospital from 1975 to 1989]. AB - From 1975 to 1989, 12 patients with pemphigus vulgaris (PV) and 19 with pemphigus foliaceus (PF) were treated with systemic or topical corticosteroids at the Nara University Hospital. All 12 patients with PV were treated with oral corticosteroids (initial dose of prednisolone: 15-70 mg/day) and 4 of 12 patients showed prolonged clinical remission (up to 9 years) without corticosteroids. Of 19 patients with PF, 16 patients were treated with oral corticosteroids (initial dose of prednisolone: 8-40 mg/day) and 3 patients were treated with only topical application of corticosteroids. In PF, 7 of 16 patients treated with systemic corticosteroids and all 3 patients treated with topical corticosteroids also showed prolonged clinical remission (up to 10 years). These observations suggest that most of the patients with pemphigus respond well to the treatment of relatively small or moderate dosage of corticosteroids. PMID- 1942588 TI - [A case of systemic lupus erythematosus with the central nervous system manifestations (CNS-lupus) mimicking herpes simplex encephalitis (HSE)]. AB - A 21-year-old male with SLE developed seizure, loss of consciousness and focal signs referable to involvement of the front-temporal brain regions. MRI (magnetic response imaging) image revealed high signal areas in the temporal lobes. By these findings, herpes simplex encephalitis (HSE) was suspected at first. But neither isolation of herpes simplex virus nor HSV specific IgM by ELISA was detected. Acyclovir administration by intravenous infusion was'nt effective but corticosteroid pulse therapy was effective. The level of anticardiolipin antibody was very high. Finally, the diagnosis of CNS-lupus with HSE-like characteristics was made in this case. PMID- 1942589 TI - [A case of smoldering ATLL in high risk family and familial double infection of HTLV-1 and HBV]. AB - A 35-year-old male from Kagoshima prefecture developed nodules with asymptomatic erythema on both upper eyelids, both hands and upper right leg in April 1986. On April 10, 1987, biopsy of skin lesions revealed numerous atypical CD4 positive lymphocytes which had invaded the dermis around the vessels. Analysis of serum showed positive antibody titer (X40) against the human T lymphotropic virus type I (HTLV-I) with some flower cells evident in peripheral blood; however, no infiltration into bone marrow or lymph nodes could be seen. Lymphocytes from peripheral blood and from the skin lesion of the right leg showed monoclonal integration of HTLV-I proviral DNA. Chronic active hepatitis B virus (HBV) was also a complicating factor. Familial study revealed all three family members to be infected with HTLV-1 as well as HBV. Proviral integration of HTLV-I was the intermediate type in two out of the three. From the results, a diagnosis of smoldering adult T cell leukemia-lymphoma (ATLL) was made in this patient with high risk to family members. Herein we discuss the development of ATLL in this case and infection among family members. PMID- 1942590 TI - [Cell kinetic effects of crude coal tar application plus long wave ultraviolet radiation on normal and hyperproliferative epidermis of guinea pig skin]. AB - This study investigated the cell kinetic effects of combined treatment with crude coal tar and long wave ultraviolet (UVA) radiation on the normal and n-hexadecane induced hyperproliferative epidermis of guinea pig skin. Flow cytometry was used to determine the proportion of cells in S phase (S fraction) and G2 + M phase (G2 + M fraction). Bromodeoxyuridine incorporation was used to determine the labeling index. Conventional histologic techniques were used to observe the mitotic index. In the normal epidermis after a single treatment with tar and UVA (1 J/cm2) or tar alone, the labeling index showed an initial decrease of 4 hr duration followed by moderate increase. The initial decrease was more pronounced in the tar-UVA-treated epidermis than in the tar-treated epidermis. The mitotic index was depressed during the first 12 hr. S- and G2 + M fraction showed no changes during the first 12 to 18 hour, and then increased in varying degrees. In the hyperproliferative epidermis after two applications of tar and UVA (1 and 4J/cm2) or tar alone, the labeling index was depressed during the first 12 hr, and mitotic index was below the control level until the 36 hr. The inhibitory effects on DNA synthesis and mitosis were more pronounced in the tar-UVA-treated epidermis than in the tar-treated epidermis. The S- and G2 + M fraction exceeded the control level in varying degrees during the whole experimental period. The results indicate that tar inhibits the epidermal DNA synthesis and mitosis by itself, and that the inhibitory effects of tar are intensified by the radiation of UVA. PMID- 1942592 TI - [Skin penetration of antimicrobial agents in rats]. AB - Skin penetration of various antimicrobial agents was studied in rats. Skin concentration/serum concentration ratios were classified into three groups, i.e. group I with ratio greater than or equal to 0.7, group II with the ratio 0.7-0.4 and group III with the ratio less than or equal to 0.4. The drugs of group I were OFLX, CPFX, LFLX, FLRX, SPFX, AMK, EM, RXM, CAM, CLDM. The drugs of group II were ABPC, CVA/AMPC, CVA/TIPC, CEX, CED, CXD, CTM-HE, CXM-AX, CPZ, CBPZ, TFLX, ASTM, MINO. The drugs of group III were AMPC, CCL, CDX, CPDX-PR, CFTM-PI, CTZ, CEC, CEZ, CTM, CMZ, CZON, MCR, IPM/CS. Factors which may influence the skin penetration were discussed, but no definite conclusion has not been obtained. PMID- 1942591 TI - [The partial characterization of neutrophils' and lymphocytes' chemotactic factors from murine anagenic hair bulb extract]. AB - Sephadex G-75 gel filtration of murine anagenic hair bulb extracts (HBE) showed two peaks with chemotactic activity. Peak I (m.w. 63 +/- 4.6 KD) was chemotactic for both neutrophils and lymphocytes, and Peak II (m.w. 47 +/- 5.6 KD) was chemotactic for lymphocytes only. The neutrophil related chemotactic activity was sensitive to treatments by trypsin, pronase, neuraminidase, or heating at 100 degrees C for 10 min. With Peak I, lymphocyte related chemotactic activity was sensitive to treatments by pronase, trypsin or neuraminidase, but was unaffected by heating at 100 degrees C for 10 min. On the other hand, the same aforementioned treatments all individually inactivated the Peak II lymphocyte related chemotactic activity. Intradermal injection of Peak I fractions into guinea pigs induced infiltration of neutrophils and mononuclear cells, and that of Peak II induced the infiltration of mononuclear cells. These findings suggest that normal C3H murine anagenic hair bulb contains three different chemotactic factors related to neutrophils and lymphocytes. PMID- 1942593 TI - [Urticarial erythema with neutrophilic infiltration--correlation of cutaneous vascular changes with clinical severity]. AB - Twenty-seven cases of urticarial erythema with predominantly neutrophilic infiltration in the upper dermis were examined clinically, histologically and serologically. Their condition persisted longer than common urticaria, with transitory high fever and arthralgia being noted frequently. Based on histological examination results, the patients were divided into three groups. Ten patients with histological findings of leukocytoclastic vasculitis were diagnosed as urticarial vasculitis which was accompanied in 7 cases by systemic lupus erythematosus, Sjogren syndrome or viral hepatitis. This group frequently showed hypocomplementaemia and multiple organ involvement such as hepatitis and nephritis. An immunofluorescence study demonstrated immunoglobulin and/or complement components to be deposited in the vessel walls of upper dermis, thus implicating type III allergy in the pathogenesis. The second group consisted eight patients with moderate infiltration of neutrophils toward the vascular walls though vasculitic changes were not apparent. Systemic lupus erythematosus and Sjogren syndrome were noted in 5 of these patients but multiple organ involvement was relatively quite infrequent. Antihistamines and even systemic corticosteroids failed to have any effect in the majority of the patients on these two groups. The remaining nine patients constituting the third group showed neither neutrophilic infiltration toward vessel walls nor vascular damage and there was no multiple organ involvement. Bacterial infection of upper respiratory tract appeared to possibly be a trigger in most of these patients for whom antibiotics were effective as treatment. In conclusion, histological examination is particularly important for cases such as the present cases for accurate diagnosis and deciding appropriate treatment. PMID- 1942594 TI - [A case of malignant hemangioendothelioma effectively treated with intra-arterial continuous infusion of interleukin-2]. AB - A case of Malignant Hemangioendothelioma (MHE) effectively treated with intra arterial continuous infusion of recombinant interleukin-2 (rIL-2) was experienced. The Pt, a 82-year-old women, presented herself in our hospital with a complaint of the tumor in right-frontal region. Based on clinical and pathological findings, the Pt, was diagnosed as MHE. Increase of LAK (Lymphokine activated killer cell) activity was observed during treatment with intra-arterial continuous infusion of rIL-2. In addition, decrease of tumor was started when LAK activity showed high value. We mainly discussed about treatments for MHE and mechanism of these therapies by use of data of this case and other autho's papers. PMID- 1942595 TI - [Generalised type of acquired dermal melanocytosis]. AB - A 55 year-old man with a leiomyosarcoma of the rectum and its multiple metastatic lesions in the liver was evaluated for the presence of multiple pigmented macules. The initial lesion was noticed on the face at the age of 53 years old, and then extended to the upper extremities and the back, and became darkened. On physical examination, there were extensive and multiple blue gray macules on the face, upper extremities, shoulders, and the back. Grey flecks on the both palpebral conjunctivas, blue-grey flecks on the palate and blue and brown pigmentation of the gingiva were also noticed. The serum levels of alpha-MSH and growth hormone showed about twice as much as normal range. By light and electron microscopic examinations, pigment bearing cells were identified as dermal melanocytes. From these findings, we diagnosed this case as a generalized type of acquired dermal melanocytosis. PMID- 1942596 TI - [Sweet's syndrome with pregnancy]. AB - A 31-year-old pregnant woman had eruptions on her wrist, face and neck. We diagnosed her as having Sweet's syndrome from clinical symptoms, histopathological and laboratory findings. We successfully treated her with prednisolone and there are no relapses after delivery. We studied her polymorphonuclear leukocyte activity by the polarization assay with N-formyl methionyl-leucyl-phenylalanine as a chemoattractant and it is higher than that of control. It is known that Sweet's syndrome is accompanied with collagen diseases and malignant diseases or others as underlying diseases or conditions. Three cases of Sweet's syndrome associated with pregnancy have been reported before and this is the first one in Japan. PMID- 1942598 TI - Effect of a modified rectus tuck on anterior ciliary artery perfusion. AB - Strabismus surgery results in the permanent interruption of anterior ciliary blood flow, predisposing the eye to anterior segment ischemia (ASI). A primate model was used to assess the effectiveness of a new muscle-scleral tuck for preserving anterior ciliary artery circulation. The model consisted of removing 3 rectus muscles from both eyes of 2 rhesus monkeys, then performing a tuck on the inferior rectus (IR) right eye while leaving the left IR as a control. Four weeks later, a modified tuck was performed on the virgin left IR. Fluorescein iris angiograms of both eyes were obtained, and preoperative angiograms at 5-15 sec. showed normal 360 degrees perfusion. Postoperative follow-up angiograms showed segmental superior temporal filling defects and preservation of perfusion in the distribution of the IR. Comparison of fellow eyes tucked vs control IR showed no difference in the filling pattern in both monkeys. Comparison of the same eye before and after tuck also showed essentially the same filling pattern in all 4 eyes with preservation of inferior circulation. Our conclusion is that the modified tuck preserves the anterior ciliary blood flow and may be useful as a muscle-strengthening procedure in patients predisposed to developing ASI. PMID- 1942597 TI - Fibronectin in the trabecular meshwork: immunofluorescent and immunoelectron microscopic findings. AB - We examined the fibronectin (FN) secretion of cultured trabecular meshwork (TM) cells in a normal human eye by indirect immunofluorescent technique using mouse anti-human FN monoclonal antibody and FITC-conjugated goat anti-mouse IgG. To localize FN on frozen sections of normal TM, which were obtained from 7 enucleated eyes owing to traumatic eyeball rupture, the same indirect immunofluorescent method was used. Immunoelectron microscopy was applied to demonstrate the distribution pattern of FN in the normal TM of 2 human eyes using an avidin-biotin-peroxidase complex method. In the tissue culture of TM, the TM cell walls and extracellular matrices showed an intense staining with antibody to FN. Indirect immunofluorescent staining of FN on frozen sections of TM showed strong positive reactions in the subendothelial region. There was no reaction in the central core of the trabecular beam. Immunoelectron microscopy revealed the reaction products to FN in the areas lining the trabecular endothelial cells. PMID- 1942599 TI - Evaluation of congenital colour vision deficiencies. AB - Three hundred patients who have congenital colour vision deficiencies were examined at the author's eye clinic for 3 years (1987-1990) using 5 types of colour vision tests: Hahn's, TMC's, Okuma's (new), H-R-R's colour vision tests and Double 15 Hue Test (Hahn). The results obtained from each test were quite different in type and grade, and the summarized results were considered to be the best: Type: protan 23.3%, deutan 76.0%, unclassified 0.7% Grade: mild 20.3%, medium 25.3%, strong 54.4% The frequency of coincidence both in type and grade between the summarized results and those of each test were compared, and the highest was 62.3% in Double 15 Hue Test. The efficiency of the author's colour vision test and Double 15 Hue Test were evaluated with the data in this clinical trial, and they were found to be useful for classifying the type and estimating the grade of the congenital and also acquired colour vision deficiencies. PMID- 1942600 TI - Epikeratoplasty for keratoconus. AB - The 6 eyes of 6 patients operated on using keratoconic epikeratoplasty are evaluated, and the mean 11-month postoperative results are reported. Uncorrected visual acuities improved in 4 patients and were maintained in 1 patient. One patient revealed a decrease of uncorrected visual acuity in the postoperative 6th month. Two patients showed an improvement of over 2 Snellen lines. Two patients showed the same corrected visual acuity, and that of 2 patients decreased within the postoperative 6-months follow-up. There was a significant decrease of myopia in terms of spherical equivalent. As a result, 4 cases showed a postoperative refractive error from +1.0 to -2.5D. Two cases were myopic deviated, -4.0 and 5.0D, and need further observation. In all cases, there was an effective flattening of the protruding cone with a mean decrease of over 11D of keratometry readings. Complete reepithelization occurred within 12 days, (average 7.5 days) and a moderate pressure patch was used as a routine procedure to promote the reepithelization. PMID- 1942601 TI - Measurement of the tear meniscus height using 0.25% fluorescein sodium. AB - Measuring the tear meniscus height (TMH) is easy after fluorescein installation, but the TMH after fluorescein instillation is higher than the TMH before fluorescein instillation. Therefore, we measured the time that the TMH after fluorescein instillation became the same with the TMH, we studied the difference in the TMH between normal eyes and dry eyes. The TMH 0.19 +/- 0.05 mm in the normal eyes and 0.10 +/- 0.04 mm in the dry eyes, and there was a significant difference between the 2 groups. The time that the TMH after fluorescein instillation became the same with the TMH before fluorescein instillation was 2.19 +/- 0.81 min. in the normal eyes and 2.29 +/- 0.73 min. in the dry eyes. Within 4 min. after fluorescein instillation, the TMH became the same with the TMH before fluorescein instillation in all cases and the height persisted until 7 min. after fluorescein instillation. Therefore, measuring the TMH will be easy if it is measured at 4-7 min. after fluorescein instillation. PMID- 1942602 TI - Long-term results of implantation of posterior chamber intraocular lens by suture fixation. AB - We reviewed the long-term results of implantation of posterior chamber intraocular lens (PC IOL) by suture fixation in 23 patients without zonular or capsular support. In terms of preoperative state, 15 were aphakic, 5 had cataracts and 3 were aphakic with concurrent corneal opacity. The latter had penetrating keratoplasty as well at the time of surgery. They were followed up for more than 1 year, and the best corrected vision remained the same or improved in all cases after surgery. The transscleral suture fixation-related complications included vitreous hemorrhage, hyphema and retinal detachment. PMID- 1942603 TI - Cryotherapy for retinopathy of incontinentia pigmenti. AB - A case with typical skin lesions of incontinentia pigmeti showed progressing retinal vascular abnormalities. So cryotherapy was done on avascular peripheral retina, and retinal vascular changes ceased. We propose that cryotherapy may be a good treatment method for progressing retinal vascular lesions of incontinentia pigmenti. PMID- 1942604 TI - Medial transposition of the lateral rectus muscle in experimentally induced medial rectus paralysis. AB - When the oculomotor nerve is completely paralyzed, the affected eye shows severe outward displacement and poor cosmetic appearance. Past results of many surgical procedures for oculomotor palsy have been generally unsatisfactory. We tried a new surgical approach experimentally, in which the disinserted lateral rectus muscle was used as an adductor by medial transposition of the muscle. Five adult cats underwent disinsertion of the medial rectus muscle of both eyes to induce iatrogenic medial rectus paralysis. The disinserted medial rectus was removed as far back as possible to prevent reattachment. Then, the right lateral rectus muscle was disinserted and passed beneath the superior rectus muscle and resutured to the sclera 4mm superoposterior to the medial rectus insertion site. After excision of the bilateral medial rectus, a large exotropia of an average 47.6 delta (42.0-55.5 delta) was induced. The medial transposition of the right lateral rectus produced an average 36.6 delta (24.8-45.8 delta) correction of the exotropia. A satisfactory cosmetic result was achieved by this procedure. PMID- 1942605 TI - [Duodenogastric reflux and gastric carcinogenesis in rats]. AB - This study was designed to investigate the role of duodenogastric reflux in the genesis of gastric carcinoma in rats. One hundred and two rats were subjected to one of following three surgical procedures: Antiperistaltic duodenogastric reflux (ADGR) was made for duodenal juice to reflux through the pylorus into the stomach. Isoperistaltic duodenogastric reflux (IDGR) was prepared for duodenal juice to reflux into the stomach through the gastrojejunostomy made at the greater curvature of the fundus. Simple laparotomy was employed as control. On the 50th postoperative week all surviving animals were killed and examined. No carcinoma was found in any of the 20 control animals. In seven of 17 animals (41%) with ADGR and five of 13 (31%) with IDGR, carcinoma developed in the glandular stomach. The significant difference between ADGR and control group, and IDGR and control group was recognized at the incidence of occurrence of gastric cancer, respectively (P less than 0.01). The carcinomas were located at the prepyloric antrum in ADGR and at the fundus neighbouring gastrojejunal anastomosis in IDGR. The findings suggests that duodenogastric reflux may be an important factor in gastric carcinogenesis. PMID- 1942606 TI - [A study on BrdU labelling index of gastric cancer using in vitro labelling method]. AB - In order to reveal the effect of environmental factors to BromodeoxyUridine labelling index (BrdU L.I.) and its usefulness as clinicopathological information, 522 specimens obtained from 121 lesions of gastric cancer were studied. Five hundred twenty two specimens in which BrdU had been incorporated using an in vitro labelling method were divided into 3 groups according to their degree of necrosis and cell infiltration. The average L.I. of the specimens with no or slight necrosis was 23.3 +/- 8.7%, medium, 14.2 +/- 10.0%, and severe necrosis, 6.6 +/- 3.8%, with no or slight cell infiltration, 25.3 +/- 9.5%, medium, 21.0 +/- 7.1%, and severe cell infiltration, 21.2 +/- 6.1%, therefore L.I. correlated to necrosis and cell infiltration. Representative values for each lesion were adopted and compared using 3 methods. In method A, a representative value of the L.I. for each lesion was chosen using all biopsy specimens, method B using specimens without necrosis, and method C, specimens without necrosis and cell infiltration. L.I. correlated to stage and the lymphnode metastasis only using methods, B and C and more strictly using method C. Necrosis and cell infiltration should be considered in adopting a representative value of the L.I. for each lesion. Method C is considered to be a best among the three studied, and the L.I. of gastric cancer may be considered a clinicopathological marker. PMID- 1942607 TI - [Studies of morphometric analysis and cell cycle of gastric epithelia of rat administered minimal mixed bile acids]. AB - The gastric epithelia of the rat after administrated with the minimal mixed bile acids and lysozyme for 9-weeks were studied using morphometric analysis and anti Bromodeoxyuridine staining immunohistochemistry. Our results show that the atrophic changes and increased anti-BrdU antibody staining positive and mitotic cells of the pyloric glands area in the group administration only bile acids. Lysozyme inhibited bile acids activation on these changes of this area. PMID- 1942608 TI - [Prevalence of K-ras gene mutations in human colorectal cancers]. AB - It has been reported that mutations in the human ras gene family convert these genes into active oncogenes. In the present study using in vitro gene amplification by the polymerase chain reaction (PCR) and mutation detection by the oligonucleotide hybridization assay, a total of 86 colorectal cancers were analyzed for the point mutations at codon 12 and 13 of K-ras genes. Mutations were present in 33 of the 86 colorectal cancers examined; 32 of the 33 mutations were at codon 12 of this gene and one of them was at codon 13. There was no apparent correlation between the presence of a ras gene mutation in a carcinoma and its anatomical location, level of differentiation, depth of invasion, degree of lymphnode metastasis or stage of progression, however, the high incidence of K ras mutations was observed in early stage carcinomas (depth m and sm). This results support the concept that the point mutation of K-ras gene is early event in tumorigenesis of colorectal cancer. PMID- 1942609 TI - [Relationship between the condition of the liver in patients and carriers with hepatitis B virus (HBV) and whether there is intrafamilial clustering of HBV]. AB - We analyzed the relationship between the presence of intrafamilial clustering of infection with hepatitis B virus (HBV) and the condition of the liver. Parents and siblings of subjects infected with HBV, some patients and some carriers, were tested for the presence of HBsAg, HBeAg, HBeAb, and liver damage. Then the original subjects with HBV were classified by the results into one of three groups. The subjects in the group without clustering had a higher rate of being seronegative for HBeAg than the groups with clustering, at all ages (P less than 0.01; test). Of the original subjects who were seronegative for HBeAg, the group without clustering had less damage of the liver than the groups with clustering. Of the subjects infected by horizontal transmission, the group without clustering had a higher rate of being seronegative for HBeAg and less damage of the liver than the groups with clustering. Subjects with HBV in a family with members who had normal liver function and who were seronegative for HBeAg were less likely to develop chronic hepatitis B than such subjects in a family with members having chronic liver damage. Thus the presence of intrafamilial clustering might affect the chance of subjects with HBV developing liver damage. The mode of infection and some genetic factors in the infected subjects seem to contribute to the condition of subjects with HBV infection. PMID- 1942610 TI - [Hepatic protein synthesis rate as an index of hepatic functional reserve in human liver]. AB - Hepatic protein synthesis rate (HPS) in human livers were measured to evaluate hepatic functional reserve. HPS of 34 patients who underwent operations were studied and were divided into 4 groups. Normal liver (n = 7), obstructive jaundice (n = 9), liver cirrhosis (n = 8) and other hepatic dysfunction (n = 10). HPS in normal liver was 6.9 +/- 3.0 nmol/mg wet wt./10 min. HPS in obstructive jaundice liver was 17.1 +/- 10.3, and HPS in liver cirrhosis was 47.5 +/- 17.8. There were significant differences among these three groups. HPS correlated well with cholinesterase (r = -0.6533, P less than 0.01) and ICGR15 (r = 0.7315, P less than 0.01). In 15 patients who received hepatectomy, relations between HPS and postoperative complication were studied. There were no complications in patients whose HPS were less than 20 nmol/mg wet wt./10 min. in major hepatic resection and in patient whose HPS were less than 40 in a segmentectomy. Even if HPS were elevated, the operations were safe in subsegmentectomy and partial hepatectomy. So HPS would be one of the good indices to evaluate hepatic functional reserve. PMID- 1942611 TI - [Analysis of muscarinic receptors on rat pancreatic acini by using 125I quinuclidinyl benzilate and N-[3H]-methylscopolamine]. AB - To analyze muscarinic receptors on rat pancreatic acini, we studied the binding of 125I-quinuclidinyl benzilate (125I-QNB) and N-[3H]-methylscopolamine ([3H] NMS) to these acini. Binding of 125I-QNB and [3H]-NMS to acini was specific and reversible. 125I-QNB bound to low affinity site, which was not recognised by [3H] NMS. However, nonspecific binding of 125I-QNB to acini was very high (46%), so 125I-QNB may be inadequate to analyze muscarinic receptor on pancreatic acini. Muscarinic receptors are classified in two groups, M1 and M2, according to affinity of pirenzepine which binds to M1 receptor selectively. Pirenzepine was 530 times less potent than atropine in inhibiting the binding of 125I-QNB, and 250 times less potent than atropine in inhibiting the binding of [3H]-NMS. These results suggest that muscarinic receptors on pancreatic acini are mainly M2 receptors. PMID- 1942612 TI - [Changes of the urinary excretions of hydroxyproline and fibronectin fragment in acute pancreatitis]. AB - Urinary excretions of hydroxyproline and fibronectin fragment (FN fragment) were serially investigated in the patients with acute pancreatitis or acute exacerbation of chronic pancreatitis. While urinary excretion of FN fragment showed the maximal level on the first day of admission, high levels of urinary hydroxyproline were observed on the second to fifth day. As to the changes in the individuals, peak level of urinary FN fragment always preceded that of hydroxyproline. And it was assumed that the elevation of FN fragment excretion on the early phase of pancreatitis reflected tissue damages of pancreas itself and complicated organs, and following elevation of hydroxyproline showed enhanced collagen metabolism induced by acute inflammation and tissue damage. According to the severity of pancreatitis, urinary excretion of FN fragment on the first day increased, and it was therefore suggested that urinary FN fragment would be one of the parameters for the assessment of the severity of acute pancreatitis. PMID- 1942613 TI - [A case of cavernous hemangioma of the jejunum manifested by repeated melena]. PMID- 1942614 TI - [Intramural hematoma of the small intestine caused by anticoagulant therapy: report of a case]. PMID- 1942615 TI - [Cases of chronic hepatitis which showed clear changes of serum levels of 7S collagen in response to steroid and interferon therapy]. PMID- 1942616 TI - [Liver dysfunction in the second stage of syphilis]. PMID- 1942617 TI - [A case of primary biliary cirrhosis associated with sarcoidosis]. PMID- 1942618 TI - [A case report of an infected liver cyst: significance of ethanol infusion therapy]. PMID- 1942619 TI - [A case of pancreatic pseudocyst with high level of CEA in the cyst fluid]. PMID- 1942620 TI - [Sensitive enzyme immunoassay by using chemiluminescence for the determination of serum c-erbB-2]. PMID- 1942621 TI - [Effects of a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase on cholesterol gallstone formation in prairie dogs]. PMID- 1942622 TI - [Proceedings of 1991 meetings of local subsections of the Japanese Society of Gastroenterology. Abstracts]. PMID- 1942623 TI - [Involutional osteoporosis]. PMID- 1942624 TI - [Prevention and treatment of dementia: what should we do today?]. AB - Three studies were conducted on elderly patients with dementia. A case of control study on life styles before falling ill revealed that "intake of sweets" was significantly associated with clinically diagnosed dementia of the Alzheimer's type. Evaluation of treatments of outpatients suggests that proper care and some kinds of neuroleptics are useful for alleviation of abnormal behavior such as agitation, wandering, hallucination, insomnia and depression, but not for improvement of cognitive function and memory. A study on caregivers of elderly demented patients was undertaken to determine the relationship between the components of burden and symptoms of patients. Insomnia and abnormal behavior of patients correlated with physical and mental components of the burden of caregivers. Memory disturbance, psychological symptoms and deterioration in ADL correlated with physical burden. These studies indicate that symptoms accompanying dementia such as insomnia, wandering, hallucination and agitation should be the treated intensively for the purpose of improvement of the quality of the lives of patients and caregivers. PMID- 1942625 TI - [Depression in late life]. AB - Depression is the most common psychiatric condition encountered in elderly people. The present paper intended to first review past epidemiological studies on depression in late life and secondly to investigate the symptomatological characteristics of depression in the elderly. The author also report significant results of a therapeutic approach to late-life depression, including antidepressant drug treatment and non-convulsive electric shock therapy. Previous epidemiological studies on prevalence rate of late life depression can be divided into two distinct groups according to their different methodologies including subjective and objective evaluations. Approximately 30% subjectively evaluated and 3% objectively evaluated in elderly people older than 65 years of age were depressed with depressed women outnumbering men approximately 2 to 1. Comparisons of the symptomatological characteristics were made in an extremely wide series of 104 depressed in-patients. Depressed patients with hypochodriacal complaints, pseudo-dementia, delusion and suicidal urges increased with aging. Depressed patients with a genetic factor decreased with aging, suggesting that the depressed patients in late life seems to have multiple etiological factors. We intended to correlate the plasma levels of various antidepressant drugs to the age of the depressed patients. There were significant positive correlations between the plasma levels and the age in patients with tricyclic antidepressant (amoxapine, dothiepin) treatment while on the other hand, no significant correlation was found between the two values in the patients with non-tricyclic antidepressant (setiptiline) treatment. These results suggest that non-tricyclic antidepressant drug should be selected for the treatment of depression in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942626 TI - [Falls and fractures in the elderly]. PMID- 1942627 TI - [Urinary incontinence in the aged]. AB - With increasing number of the elderly, the problem of urinary incontinence might become as serious as those of dementia and the bedridden. But strategy for urinary incontinence of the aged lay behind those for the other two. Not only does urinary incontinence significantly disturb the activity and social participation of patients it also increases the total cost of care and the number of long-stay patients in hospitals, causing enormous expenses. The relative and absolute decrease of the younger generation, coupled with the tendency towards nuclear families, makes the national policy of home-care system for the aged patients difficult. Now we must take new steps to cope with this situation. Since urinary incontinence is generally caused by some disease, medical care might cure it or simplify its management in many cases. However, considering the increase in the number of elderly urinary incontinent patients, the number of incontinence care professionals is very small in our country. A help from general practitioners who are usually in contact with age patients, is indispensable. To assist them, we are now compiling a manual on how to assess and manage urinary incontinence in the elderly, based on the useful classification of Brocklehurst. The causal diseases of transient urinary incontinence are familiar to the general practitioners and may be treated by them relatively easily. For the treatment of the causal diseases of the established urinary incontinence the patients should be sent to specialists, after first aid if necessary. Some advice concerning to pharmaceutical therapy, based on my daily clinical experience, are added. PMID- 1942628 TI - Urinary incontinence in the geriatric population. AB - Urinary incontinence in the geriatric population is prevalent, morbid, and costly. Despite the high prevalence and adverse effects, many incontinent geriatric patients do not undergo any type of diagnostic evaluation. Assessment of incontinence in this patient population should focus on identifying reversible factors that may contribute to the incontinence, determining whether the patient should be referred for further evaluation before initiating treatment, and pinpointing the cause(s) of the incontinence so that appropriate treatment can be instituted. Many different therapeutic modalities can be helpful for geriatric urinary incontinence, including behavioral, pharmacologic, and surgical approaches. Chronic catheters and diapers should generally not be used as the initial treatment, and be reserved for patients who fail more specific treatment approaches. Although it may not be possible to cure the incontinence, it is almost always possible to ameliorate the problem, and prevent discomfort, complications, and excessive costs. PMID- 1942629 TI - [Iatrogenic diseases in the elderly]. AB - The growing number of drugs used to treat various diseases and the growing number of invasive procedures used for diagnosis and therapy have generated many iatrogenic diseases. Elderly patients are more likely than the young to react adversely to drugs since the physiological functions of the organs, especially of the kidneys, decrease and pharmacokinetic characteristics altered. In addition, multiple disease states are common in the elderly, and multiple drugs are consequently prescribed. In the present study, adverse effects of so-called "cerebroactive drugs" and "cerebral vasodilators" are discussed. More than 30 kinds of these drugs are on the market in Japan and are widely prescribed for "chronic cerebrovascular diseases" and "dementia syndromes" in the elderly. In contrast, they are rarely used in Western Europe and not on the market in the United States. Among them, calcium hopantenate was the first of "cerebral activators" and was the most popular. In 1986, however, the first cases of toxic encephalopathy induced by calcium hopantenate were reported. It resembled Reye syndrome, showing coma, hepatic failure, lactic acidosis and hypoglycemia and was frequently fatal. More than 47 victims including 11 fatal cases have been reported since. Flunarizine, a cerebral vasodilator, produced high rates of parkinsonism and depression. Multicenter studies have revealed that these side effects occurred in 10-30% of the elderly patients who had taken it. These symptoms usually appeared several months after flunarizine was started. Some of the adverse effects of the drugs may be unpredictable and inevitable, but most of them can be prevented or reduced if physicians are more careful with their patients, and drugs and their adverse effects.2 PMID- 1942630 TI - [VCAP combination chemotherapy of multiple myeloma in the aged]. AB - A comparative study between patients aged over 65 (elderly group) and those under 65 (non-elderly group) was performed to determine the therapeutic efficacy of combination chemotherapy with vincristine, cyclophosphamide, Adriamycin and prednisolon (VCAP) for untreated multiple myeloma as both induction and maintenance therapy. The subjects selected were 38 patients with untreated myeloma who presented over the 7.5 years from 1982 to 1989 (June), consisting of 14 aged over 65 and 24 aged under 65. According to the classification of Durine and Salmon, 3 and 11 patients of the elderly group were stage II and III cases, respectively, while the numbers were 8 and 16 in the non-elderly group. The results defined by Imamura's criteria showed a 61.3% (9/14) partial remission rate in the elderly group and a 66.7% (17/24) rate in the non-elderly group. The 50% survival was 43 months in the elderly group and 65.5 months in the non elderly group, with no significant difference between the groups. Thus, VCAP therapy for the induction of remission and maintenance for multiple myeloma therapy resulted in satisfactory prolongation of life in both groups, with a low incidence of the adverse reactions. PMID- 1942631 TI - [Changes in the blood cell counts with aging]. AB - We analyzed the blood cell counts and serum levels of total protein (TP), total cholesterol (TC) and triglyceride (TG) of 2,231 healthy subjects (1,295 men and 936 women) between age 20 and 99 years in order to clarify the following two subjects. (1) In the approximately 10 years since the report of Shirakura et al in 1978, eating habits have improved and the average life expectancy has extended in Japan. Is there any effect of such betterment on blood cell counts of the aged? (2) It has been pointed out that quality of everyday life, such as staying at home but not in an old-age home, working, traveling, and so forth, had an influence on the blood cell counts of aged. Is there any difference between the blood cell counts of people under 60 years and those of people older than 60 years who have a good quality of life as mentioned above? The hemoglobin concentration, red blood cell count, and hematocrit value began to decrease in men in their sixth decade and in women in their seventh decade and the change was more prominent with advancing age, especially in men. The white blood cell count and platelet count tended to decrease with advancing age. The serum levels of TP, TC, and TG also declined with age in those over 60 years of age. These results confirmed that the hemoglobin concentration, red blood cell count, and hematocrit value decrease in the elderly subjects as they grow older and it may be considered that reduced ingestion of protein is one of the causes of the phenomenon. PMID- 1942632 TI - [Relationship among glycated compounds, superoxide dismutase activities, and other related analytes in diabetic patients classified by ages]. AB - Among several glycated compounds (GC) which are based on Maillard reaction, glycated hemoglobin (HbA1c) and fructosamine (FRA) have been utilized widely as a markers of diabetes. Recently, glycated albumin (GA) has been pointed out as a new indicator. For the determination of GA, spectrophotometry combined with an affinity column method has been mainly used, however the procedure is complicated. Recently a two-column HPLC method (ion-exchange column and affinity column) has been developed by Shima. We have evaluated a GA analyzer GAA-2000 based on Shima's method. After a series of fundamental and performance evaluation studies, the GAA-2000 was found to be appropriate for our study. Reference values obtained from this equipment were 10.56-16.87%. Correlation coefficients based on GA using diabetic and diabetic nephropathy patient specimens (n = 87) were: FRA (r = 0.944) greater than HbA1c (r = 0.842) greater than Glucose (r = 0.510) Superoxide dismutase (SOD) and lipid peroxidase (LPO) with are produced in relation to active oxygen did not show a good correlation. Although we tried classify the patients according to juvenile (20-39), middle (40-64) and senile (greater than 65) the method of Asada et al., we could not find any distinct tendencies. PMID- 1942633 TI - [Evaluation of the measurement of plasma fructosamine concentration in aged subjects]. AB - Recently, plasma fructosamine concentration has been used as an indication of mean plasma glucose level preceding at last 1 to 2 weeks. In the present study, to characterize the clinical significance and problems of plasma fructosamine concentration in aged subjects (greater than or equal to 65 yrs), we determined plasma fructosamine concentration as well as serum albumin, total protein, HbA1, AbA1c and fasting plasma glucose concentrations in 81 (less than 65 yrs) non diabetic subjects (group A), 161 aged (greater than or equal to 65 yrs) non diabetic subjects and 26 aged diabetics (group D). Aged non-diabetic subjects were further classified into 75 subjects with good ADL (group B) and 86 with poor ADL (group C). The normal limit of plasma fructosamine concentration (mean +/- 2SD) in group A was 24% higher (3.1 mmol/l) than that in group B (2.5 mmol/l) but the plasma fructosamine/serum albumin ratio (F/ALB) was similar in these two groups. Plasma fructosamine correlated negatively (p less than 0.01) with age. This aging effect was explained by the reduced serum albumin in aged subjects. However, in group C, reduced plasma albumin was not associated with reduced plasma fructosamine. Plasma fructosamine corrected by albumin (F/ALB) is a useful parameter of blood glucose control in aged subjects. In aged subjects with poor ADL, HbA1, HbA1c and plasma glucose should be determined with fructosamine. PMID- 1942634 TI - [The characteristics of metabolic acidosis in aged patients with chronic renal failure]. AB - The present study was designed to clarify the characteristics of metabolic acidosis in aged patients with chronic renal failure. The subjects consisted of ambulatory cooperative patients (19 males and 18 females). Their values of creatinine clearance (Ccr) varied from 6.8 to 107.5 ml/min/1.73 m2. The relationship of Ccr to acid-base and electrolyte disturbances was investigated. The estimations of normal values in acid-base and electrolyte composition were based on the method of Hoffmann. The results are summarized as follows: 1. A high incidence of metabolic acidosis was demonstrated in patients whose Ccr values were below 20 ml/min/1.73 m2. 2. A significant positive correlation of Ccr values and plasma levels of bicarbonate (p less than 0.001) and a significant inverse correlation of Ccr values and serum levels of chloride (p less than 0.01) were observed. 3. The values of the anion gap did not change, irrespective of Ccr values. 4. Serum concentrations of potassium were inversely correlated with plasma levels of bicarbonate (p less than 0.01). Hyperchloremic normal anion gap acidosis with hyperpotassemia was the characteristic feature of metabolic acidosis in aged patients with chronic renal failure. The normal anion gap could be explained by normophosphatemia or mild hyperphosphatemia, even in the patients with advanced renal failure. PMID- 1942635 TI - [The relationship between cerebral white matter changes, mental function and blood pressure in normal elderly]. AB - The authors examined the relationship between cerebral white matter changes and mental function, blood pressure in 39 neurologically normal aged (21 males, 18 females, mean age 75.0 years) who had no latent lesions on MRI images. The severity of cerebral white matter changes was estimated by T1 value images on MRI and was measured in the bilateral frontal lobe on an axial slice at the level of the basal ganglia and in the bilateral anterior, middle, and posterior portions on axial slices at the level of the body of the lateral ventricle. Mental function was measured by the Hasegawa's dementia rating scale (HDS) and Kohs' block design test (Kohs' test). The severity of cerebral frontal white matter changes increased significantly with age (p less than 0.05). However there was no significant correlation between the severity of cerebral white matter changes and HDS, Kohs' test. The severity of frontal white matter changes correlated with the mean arterial blood pressure (p less than 0.02). These results suggest that the severity of cerebral white matter changes is not related with mental function in the normal elderly, and that the severity of frontal white matter lesions is related with mean arterial blood pressure. PMID- 1942637 TI - Quality of life of the elderly in Japan. PMID- 1942636 TI - [Clinical study on low body temperature in health subjects]. AB - During last year, 931 men aged 51.0 +/- 9.5 years participated in our hospital's 3-day health screening. Their axillary temperature were taken 3 times per day (twice each, at 6:00 a.m., 2:00 p.m. and 6:00 p.m.) during their 3-day stay and the mean axillary temperature was determined for each subject. In 72 among all subjects, the mean axillary temperature was below 36 degrees C. These 72 subjects were classified as low-temperature individuals with normal temperature below 36 degrees C. This study was designed to compare low-temperature subjects with mean axillary temperature, on various factors, such as age, degree of obesity, liver function, renal function, lipids, electrolytes, and biochemical data (blood glucose, serum amylase, and CPK). This study also included seasonal changes in these low-temperature subjects. The following results were obtained. 1) Age was most closely related to low-axillary temperature, and the degree of obesity (modified Broca-Katsura method) had second significant relation. The low-axillary temperature was in common in subjects over 60 years and was also common in obese subjects, regardless of their age. 2) No seasonal effect was observed with low temperature subjects. 3) Only the age and the degree of obesity (modified Broca Katsura method) showed negative correlation independently with the mean axillary temperature. (For age, the correlation coefficient was Y = -0.006539X + 36.491, while for obesity it was Y = -0.004536X + 36.203.) Therefore the older and the more obese the subjects, the lower the mean axillary temperature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942638 TI - The effects of recombinant interleukin 2 on HBe antigen positive chronic hepatitis B. AB - Recombinant interleukin (IL-2) was administered to 16 patients with HBe antigen positive chronic active hepatitis in which the diagnosis was ascertained histologically. In 7 of the 16 patients, a decrement of the serum HBe antigen value was observed (Group A). In group A, the findings showed an increment of peripheral Leu 11-positive cells and NK and LAK cell activity, an acute exacerbation during and after IL-2 administration, disappearance of HBc antigen observed in liver biopsy histology, and decrement of serum DNA-p activity. However, seroconversion of HBs antigen was not observed and no case showed the elimination status of continuous HB virus infection. On the other hand, in the other 9 patients (Group B), these changes were not observed and the existence of a HLA type difference between Group A and B was shown by HLA analysis. These results indicated that the immune responses mediated by IL-2 may play an important role in the development of chronic hepatitis B, and these results may be regulated genetically. PMID- 1942639 TI - Chronic active "lupoid" hepatitis and HLA system; report of 6 cases. AB - During the 12 years from 1977 to 1988 in Tottori University Hospital, 6 cases (4.2%) with chronic active "lupoid" hepatitis were encountered among 143 patients with histologically proven chronic active hepatitis. HLA antigens were studied; BW 22 and CW 1 were strongly associated, and A 11 was rather associated with the rare disorder in Japan. These results suggested that Japanese patients with chronic active "lupoid" hepatitis have different HLA markers from those in Caucasian patients, which may be attributable to rare specificity in the HLA system rather than different mechanisms of pathogenesis. PMID- 1942640 TI - The present status of active tuberculosis in a general hospital; a study of 186 cases. AB - To study the present status of TB in a general hospital, we reviewed the records of 186 patients with TB at the Saga Medical School Hospital. Ninety-two patients (49.5%) had extrapulmonary tuberculosis and 59 patients (31.7%) had complicated severe diseases. The variety of TB lesions and underlying diseases often caused diagnostic delay and misdiagnosis. In fact, 16 cases were not identified to be TB until after death. The TB prevalence was significantly high in malignant disease, diabetes mellitus, collagen disease and chronic renal failure among the total number of patients discharged. Twenty-one patients developed TB while on an intensive therapy for underlying diseases. Unfortunately, 22 patients with TB died in our hospital. These findings suggest that special care must be taken to prevent TB in a general hospital. We emphasize that early diagnosis of TB depends on the suspicion of this infection on the part of the physician. PMID- 1942641 TI - Prevention of the febrile reaction occurring on reinfusion of cell-free and concentrated autogenous ascites. AB - The febrile reaction that occurs on reinfusion of ascites was studied. Intravenous reinfusion of ascites was performed 213 times in 63 cases of ascites, which were refractory to treatment with various drugs including diuretics. In order to prevent fever on reinfusion of ascites, a screen filter and a depth filter were used; the results were more favorable with the screen filter. Fibrin was considered to be one of the substances removable by the screen filter. HPLC analysis of the filtered and concentrated ascites, after passage through the screen filter, revealed a fraction corresponding to albumin. Intravenous injection of this fraction into rabbits caused fever. Although the screen filter cannot completely prevent fever on reinfusion of ascites, it appears useful to prevent fever in some patients. PMID- 1942642 TI - Interrelation between esophageal varices, and systemic and hepatic hemodynamics in male patients with compensated cirrhosis. AB - The interrelation between endoscopic findings in esophageal varices, and systemic and hepatic hemodynamic abnormalities was studied in 76 male patients with compensated cirrhosis. Observation of these patients revealed a hyperdynamic systemic circulation, represented by an increased cardiac output and reduced total systemic vascular resistance with an enlarged circulating plasma volume and without an increase in heart rate, in comparison with 23 male patients with chronic hepatitis. In patients with cirrhosis and esophageal varices, the hyperdynamic circulatory state was closely related to the condition of the varices, in which a progress in the form was accompanied by an advance in the degree of hyperdynamism with an increase in circulating plasma volume. Whereas the extent of the varices as indicated by the location was closely related to a rise in the wedged hepatic venous pressure. The shunt volume through the portal systemic collaterals requires further study to elucidate the mechanism of hyperdynamic circulation. PMID- 1942643 TI - Autoimmune hemolytic anemia and myasthenia gravis. AB - A case of autoimmune hemolytic anemia associated with myasthenia gravis in a 33 year-old female is presented. The association of autoimmune hemolytic anemia and myasthenia gravis is a very rare event, with only eight cases reported. The known association of these two diseases is reviewed. To our knowledge, this is the first reported case in which autoimmune hemolytic anemia preceded systemic myasthenia gravis. PMID- 1942644 TI - Ebstein's anomaly with non-patent ductus arteriosus aneurysm and bradycardiac atrial fibrillation in an 80-year-old man. AB - An 80-year-old man with Ebstein's anomaly and ductus arteriosus aneurysm is reported. He was admitted with bradycardiac atrial fibrillation and right ventricular failure. For the control of brady-arrhythmia, a permanent pacemaker was implanted. Two-dimensional echocardiogram revealed distal displacement of the septal tricuspid valve. Aortography and computed tomography showed ductus arteriosus aneurysm. This is the first report of the association of Ebstein's anomaly and non-patent ductus arteriosus aneurysm. PMID- 1942645 TI - Selective IgG2,4 subclass and IgE deficiencies in an adult patient with recurrent pneumonia. AB - A 28-year-old woman with recurrent pneumonia was found to have selective IgG2, 4 subclass and IgE deficiencies. She had a history of repeated episodes of otitis media and sinusitis in childhood. Her total immunoglobulin level was slightly below the normal range, and selective deficiencies of IgG2, 4 and IgE were found. Although lymphocyte responses to several mitogens were within the normal ranges, peripheral blood mononuclear cells produced only IgM when stimulated by Staphylococcus aureus Cowan 1 and interleukin-2. Gene deletion of the IgG2, 4 subclass was not found, but polymorphism of the IgG gene was detected by DNA analysis of the patient's lymphocytes. PMID- 1942646 TI - Pleural mesothelioma after neighborhood exposure to asbestos during childhood. AB - A 38-year-old woman with pleural mesothelioma who had a history of neighborhood asbestos exposure during her childhood was demonstrated. She had no known history of occupational asbestos exposure. This is the first case of mesothelioma with neighborhood asbestos exposure reported in Japan. Previously-reported cases of mesothelioma with neighborhood asbestos exposure in the English language literature were reviewed. PMID- 1942647 TI - Recurrent Pneumocystis carinii pneumonia with long interval showing disparate radiographic findings. AB - A case of recurrent Pneumocystis carinii pneumonia with a long interval between episodes and each episode showing a different radiographic appearance is reported. The radiographic finding in the initial infectious episode was bilateral, patchy, alveolar infiltrate predominantly in the upper and middle lung zones and that in the second infectious episode, six and a half years later, showed bilateral interstitial infiltrate predominantly in the middle and lower lung zones. T cell immunity expressed by mitogen-induced T cell proliferation was clearly different in the two infectious episodes. These differences in radiographic appearance could be due, at least in part, to altered immunological states between the first and second infectious episodes. PMID- 1942648 TI - A case of sarcoidosis associated with bronchial asthma. AB - A 54-year-old woman was treated for bronchial asthma for 14 yr. In March of 1989, chest roentgenography and computed tomography (CT) revealed development of bilateral pulmonary hilar lymph node enlargement. Positive 67Ga uptake was observed in bilateral pulmonary hili. Although levels of serum angiotensin converting enzyme (ACE) and lysozyme were within normal range, biopsy specimen of scalene lymph nodes showed noncaseating epitheloid-cell granuloma, leading to the diagnosis of sarcoidosis. Steroid therapy ameliorated both sarcoidosis and bronchial asthma. Although the association of sarcoidosis and bronchial asthma is uncommon, there may be an etiological relationship between them. PMID- 1942649 TI - Changes in plasma lipids and abnormal lipoproteins in a patient with drug-induced cholestatic hepatitis. AB - Changes in plasma lipids and abnormal lipoproteins in a patient with ticlopidine hydrochloride-induced hepatitis were studied. Total cholesterol, free cholesterol and phospholipids increased markedly during cholestasis. Lipoprotein electrophoresis showed a large lipoprotein-X band and a relatively small alpha lipoprotein band. As cholestatic hepatitis improved, all plasma lipids were progressively decreased. A broad band of abnormal alpha-lipoprotein appeared for the first time with the decrease in the lipoprotein-X band. Both abnormal lipoproteins decreased further and eventually disappeared. The appearance of abnormal alpha-lipoprotein was accompanied by changes in apoproteins. These findings suggest that abnormal alpha-lipoprotein might be an intermediate metabolite of lipoprotein-X. PMID- 1942650 TI - Follow-up clinical electrophysiological studies in a patient with myotonic dystrophy. AB - A 38-year-old male myotonic dystrophy patient with left hemiblock, bradycardia and ventricular arrhythmias underwent electrophysiologic studies 19 months after he developed dizziness. Rapid and significant progression of binodal disease required implantation of a permanent pacemaker, which responded favorably. We suggest that careful monitoring or electrophysiologic studies are indicated in patients with these findings. PMID- 1942651 TI - A case with renal tubular damage: differentiation of Na reabsorption function by lithium clearance. AB - The recovery of the renal proximal and distal tubular sodium (Na) reabsorption was evaluated by analysis of the physiological metabolism of lithium reabsorbed by the renal tubules in a patient with toxic interstitial nephropathy. Administration of glucocorticoid facilitated the rapid recovery of the proximal tubular Na reabsorption (-0.63 to 3 mmol/min for 2 wk) followed by recovery of phosphate reabsorption (51 to 82% for 2 months). Distal Na reabsorption was not altered for 2 months. Although Li clearance has been previously performed in healthy volunteers, we could differentiate the recovery of the proximal and distal renal tubular function even in a diseased patient. PMID- 1942652 TI - Cerebral blood flow and metabolism in an amnestic patient with left thalamic infarction--a positron emission tomographic study. AB - A 30-year-old man with left thalamic infarction developed severe amnesia. The positron emission tomography showed a decrease in cerebral blood flow and oxygen metabolism in the left thalamus and the ipsilateral frontal cortex (-20% to -12% of asymmetry index) both at day 11 and at 5 months after onset, although amnestic symptoms certainly improved during that period. The selective hypometabolism of the cerebral cortex suggested the remote effects of neuronal fiber disconnection between the left thalamus and the ipsilateral frontal cortex, which did not parallel the clinical course. PMID- 1942653 TI - Two cases of multiple sclerosis with painful tonic seizures and dysesthesia ameliorated by the administration of mexiletine. AB - Mexiletine was administered in two patients suffering from multiple sclerosis with severe dysesthesia and painful tonic seizures. In both patients the painful tonic seizures disappeared and dysesthesia improved as well. The effects of mexiletine on painful symptoms have been previously reported in diabetic neuropathy, but not in diseases of the central nervous system. PMID- 1942654 TI - A case of bilateral cerebellar peduncle infarction. AB - A 68-year-old woman had an abrupt onset of severe headache, nausea, vertigo, difficulty in standing and dysarthria. A CT scan of the brain disclosed bilateral symmetrical round infarctions involving the middle cerebellar peduncles. She exhibited marked limb ataxia, gait ataxia, dysarthria and transient gaze nystagmus. Occlusion of the right vertebral artery associated with a stenosis of the basilar artery just proximal to the origin of the anterior inferior cerebellar arteries shown in angiograms were thought to be the cause. PMID- 1942655 TI - An autopsied case of primary epipharyngeal rhabdomyosarcoma presenting Garcin syndrome. AB - A 61-year-old housewife had complained of unilateral facial pain and had been treated as prolonged trigeminal neuralgia by a dentist. When she came to our clinic, the III-X cranial nerves of the right side were involved. A base view of the skull indicated destructive lesions of the right side middle cranial fossa, and a diagnosis of Garcin syndrome was made. Neurosurgical operation, X-ray radiation and chemotherapy improved to some extent the neurological condition temporarily. Postmortem examination showed an epipharyngeal rhabdomyosarcoma occupying the maxillary sinus, and extradural space of the cranial base on the right side. PMID- 1942656 TI - Movement disorder with abnormal copper metabolism--a case report and review of the literature. AB - We describe a neurological disease, seen in the elder sister of identical twins, with dysarthria, involuntary movements, spastic gait, slightly low serum copper, borderline low to normal serum ceruloplasmin, normal urinary copper, and a high hair copper concentration. This neurological disorder appears to differ from others associated with abnormal copper metabolism such as Wilson's or Menkes' kinky hair disease. PMID- 1942657 TI - A case of neuroleptic malignant syndrome with acute renal failure after the discontinuation of sulpiride and maprotiline. AB - A 46-year-old man developed neuroleptic malignant syndrome with acute myoglobinuric renal failure after the discontinuation of sulpiride and maprotiline treatment. He showed the characteristic features of hyperpyrexia, altered consciousness, muscle rigidity, and autonomic dysfunction. Laboratory data showed lysis of skeletal muscle cells and renal impairment. Muscle biopsy revealed necrosis and regenerative changes in muscle fibers. Renal biopsy showed focal tubulitis and interstitial infiltration of small inflammatory cells. The combination of sulpiride and maprotiline has not previously been reported to be the cause of neuroleptic malignant syndrome and acute myoglobinuric renal failure. PMID- 1942658 TI - Disorder of pericardial fluid cholesterol metabolism in cholesterol pericarditis. PMID- 1942659 TI - The ATP-sensitive K+ channel. PMID- 1942660 TI - Contraction of rat soleus muscle and the effects of hypertonic treatments. AB - The effects of exposing rat soleus muscle to solutions made hypertonic by sucrose, mannitol, or urea for a period of 60 min and then to normal solutions for a further 30 min (hypertonic treatment) on twitch, tetanus, potassium, and caffeine contractures were examined. Following hypertonic treatments, twitch, tetanic, and potassium contracture tension were altered from control. The exact effects were dependent upon the concentration of solute used and the temperature. Electrically evoked contractions were abolished following hypertonic treatment with 400 mM sucrose or mannitol at 37 degrees C but 800 mM at 22 degrees C. Urea was less effective; only after hypertonic treatment with 800 mM were contractions of rat soleus muscle abolished at 37 degrees C, while at the lower temperature contractions could not be abolished. In general, caffeine contractures were reduced by hypertonic treatments at 37 degrees C but not at 22 degrees C. Hypertonic solutions themselves caused contractures of rat skeletal muscle, the amplitude of which directly depended on the concentration of solute used and the temperature. These contractures appeared to be due to the release of intracellular calcium from its stores. In hypertonic sucrose and mannitol but not urea solutions, the twitch was reduced and then abolished. Changes in contractile responses of rat soleus muscle during and after exposure to hypertonic solutions are suggested to be due to osmotically induced changes. PMID- 1942661 TI - Effects of blood glucose concentration on ratings of perceived exertion during prolonged low-intensity physical exercise. AB - The purpose of this investigation was to determine the relationship between blood glucose concentration and perceived exertion during prolonged low-intensity exercise. After a 12-h overnight fast, seven young healthy males began bicycle exercise from 0800 h at 50% Vo2max. One hour after initiation of the exercise, 20% glucose was infused by means of an infusion pump, to maintain blood glucose concentration at a level of approximately 6.5 mM for 20 min. This was followed by 20 min of sham infusion (no glucose). This 40-min cycle was repeated until 220 min of exercise. During the first 120 min of exercise, the ratings of perceived exertion (RPE) increased gradually without any effects of the glucose infusion. Thereafter, RPE tended to decrease during glucose infusion, and finally showed a significant decrease from 180 (17 +/- 2) to 190 (16 +/- 2) min. This result showed that an increase in blood glucose concentration has a significant effect on perceived exertion, even if exercise time is prolonged. The different responses of RPE during the two phases of the exercise may be explained by the difference of glycogen concentration in muscle, because glucose infusion had no effect on RPE when muscle glycogen content was presumed to be at normal level, and was effective when glycogen in the exercising muscles was presumed to be depleted. PMID- 1942662 TI - Effects of activation of the divergent efferent fibers on the spontaneous activity of vestibular afferent fibers in the toad. AB - In anesthetized toads, spontaneous activities were recorded from single afferent fibers of three semicircular canals and three otolith organs. Since some efferent fibers ramify within the eighth nerve and innervate two or more vestibular organs, a single branchlet of the eighth nerve was disconnected from its end organ, and was electrically stimulated to activate divergent efferent collaterals leading to other vestibular organs. The stimulation elicited an inhibitory effect on spontaneous activities of about one third of the afferent population, and a facilitatory effect on those of another one third. The remaining one third was unaffected. Whether or not the inhibitory or facilitatory effect was observed in an individual unit seemed to be related to its pattern and its rate of spontaneous activity. Most of the units showing relatively high and regular spontaneous firing were insensitive to the electrical stimulation, and units with a low firing rate and an irregular pattern of activity tended to be affected by the electrical stimulation. The activation of divergent efferent fibers elicited both inhibition and facilitation on the spontaneous afferent activities in all vestibular nerve branchlets, except in the saccular branchlet, where only inhibition was elicited. Electrical stimulation of the central stump of the saccular nerve branchlet, however, could produce both inhibitory and facilitatory effects in other vestibular nerve branchlets. PMID- 1942663 TI - Discharge patterns of bulbar respiratory neurons during retching and vomiting in decerebrate dogs. AB - To determine whether bulbar respiratory neurons are active in a manner similar to respiratory motor nerves, in which diverse activity patterns have been observed in dogs, the discharge of 112 bulbospinal and 155 propriobulbar respiratory neurons was observed during retching and vomiting evoked by stimulation of the vagal nerve in decerebrate, paralyzed dogs. During retching, the respiratory activities of all respiratory neurons changed. The discharge patterns during retching were classified into seven types in accordance with the discharge phase in the retching cycle and the discharge frequency. Inspiratory bullbospinal neurons (39) in the ventral respiratory group (VRG) exhibited discharge synchronous with retches at higher (14/39) or lower (4/39) frequencies than those of their respiratory discharge, discharge between retches at higher (3/39) or lower (14/39) frequencies and discharge depressed throughout the retching period (4/39). Inspiratory bulbospinal neurons (30) in the dorsal respiratory group (DRG) and expiratory bulbospinal neurons (23) in the VRG also fired with some of the seven types of discharge. No significant difference was recognized between the ratio of the numbers of inspiratory bulbospinal neurons firing with the seven types of discharge and that of expiratory bulbospinal neurons. On the other hand, the respiratory propriobulbar neurons (73) in the VRG and those (45) in the DRG seemed to be differently activated; that is, 44% of the propriobulbar neurons in the VRG fired synchronously with retches at a higher frequency than their frequency during breathing, while only 22% of those in the DRG fired at such a high frequency with retches. However, the ratio of whole inspiratory neurons (174) exhibiting the seven types of discharge was almost the same as that of whole expiratory neurons (93). During vomiting (fictive expulsion), three of five expiratory neurons fired, but most (14/16) of inspiratory neurons did not. In conclusion, all of the activity patterns which have been observed during retching in motor fibers innervating respiratory muscles are found in both bulbospinal and propriobulbar respiratory neurons in dogs. Furthermore, since the firing patterns of inspiratory bulbospinal neurons during retching in the dogs in this study are apparently different from those in cats (Miller et al., 1990), inspiratory neurons and muscles seem to be differently organized during retching in cats and dogs. PMID- 1942664 TI - Intracellular calcium signals measured with fura-2 and aequorin in frog skeletal muscle fibers. AB - Intracellular Ca(2+)-related optical signals during and after contraction (twitch and tetanus) were measured in single frog skeletal muscle fibers with fura-2 and aequorin. In twitch response, the peaks of [Ca2+]i estimated from the in vitro calibrations of fura-2 and aequorin were significantly different (0.5 microM for fura-2 and 5 microM for aequorin). Even 30s after twitch response, the fura-2 fluorescence ratio (F340/F380) signal did not recover to the resting level before stimulation. When the stimulation frequency was increased, an increase in the resting fura-2 ratio signal became obvious and after the cessation of stimulation this increase gradually recovered to the level before stimulation. After tetanus (50 Hz for 1 s), a higher fura-2 ratio signal than that before stimulation was sustained longer than 90 s. These results indicate that the dissociation of the released Ca2+ from the intracellular Ca2+ binding sites probably takes longer time than that previously reported. The present results, therefore, demonstrate that fura-2 is advantageous for qualitative monitoring of a slight change in the resting level of [Ca2+]i, which is not easily detectable with aequorin. In addition, the problems encountered in quantitative estimation of [Ca2+]i with fura-2 are also discussed. PMID- 1942665 TI - Kinetics of the Ca(2+)-activated K+ channel in rat hippocampal neurons. AB - The kinetics of the large-conductance Ca(2+)-activated K+ channel (235 pS in symmetrical 150 mM K+) were examined in the inside-out mode of the patch clamp technique. The open probability of the channel increased when [Ca2+]i, [Sr2+]i, or [Ba2+]i was increased. The [Ca2+]i-response relation was fitted with a Hill coefficient of 2 and half-maximum concentrations of 185, 80, 14.5, and 5.5 microM at -40, -20, +20, and +40 mV, respectively. The channel was blocked by TEA or Ba2+. The open-time histogram showed a single exponential component and the closed-time histogram showed at least two exponential components at various [Ca2+]i. Increasing [Ca2+]i decreased the time constant of the slow component of the closed-time histogram. Cell-attached patch recording revealed activation of the large-conductance Ca(2+)-activated K+ channel (BK channel) during the action potential. The deactivation time course was consistent with the fast after hyperpolarization. A minimum model of the channel, close(2)-close(1)-open, where the transition from close(2) to close(1) requires the binding of 2 Ca2+, reconstructed quick activation of the channel if [Ca2+]i of 40 microM was assumed. PMID- 1942666 TI - Age-related changes in rates of basal secretion of immunoreactive vasoactive intestinal polypeptide and dopamine into pituitary stalk blood from the hypothalamus in anesthetized male rats. AB - Age-related changes in prolactin (PRL) in systemic blood plasma, and in secretions of hypothalamic vasoactive intestinal polypeptide (VIP), an important candidate for PRL-releasing factor, and dopamine, a PRL-inhibiting factor, into the pituitary stalk blood were investigated. The experiments were performed on male urethane-chloralose-anesthetized Wistar rats of three different ages, i.e., (1) adult rats 5-8 months old, (2) middle-aged rats 12-15 months old, and (3) aged rats 24-26 months old. The concentration of immunoreactive PRL (iPRL) in systemic blood plasma of the aged rats was significantly higher than that of the adult rats (p less than 0.01). The secretion rate of hypothalamic immunoreactive VIP (iVIP) into the pituitary stalk blood was unchanged during aging, while that of dopamine was markedly increased in the aged rats in comparison with the value in both adult and middle-aged rats (p less than 0.01). These results indicate that the basal secretion of hypothalamic VIP is well maintained, while that of hypothalamic dopamine is augmented in aged rats with hyperprolactinemia. It can be assumed that the increase in the pituitary PRL secretion is a primary event during aging in rats, and that a high circulating level of PRL may facilitate the hypothalamic dopamine secretion through the activation of a negative feedback system of the hormone. PMID- 1942667 TI - Arachidonic acid induced increase in intracellular free calcium in guinea-pig hepatocytes. AB - Arachidonic acid (AA) caused elevations of intracellular free Ca2+ concentration ([Ca2+]i) measured by fura-2 fluorescence digital imaging microscopy in isolated guinea-pig hepatocytes. AA-induced increase in [Ca2+]i could still be observed when extracellular Ca2+ was chelated by EGTA, and was not influenced by either cyclooxygenase or lipoxygenase inhibitors. These results suggest that AA itself rather than its metabolites has direct effects on intracellular Ca2+ mobilization, causing the elevation of [Ca2+]i. PMID- 1942668 TI - Limitations due to unstirred layers in measuring channel response of excised membrane patch using rapid solution exchange methods. AB - The Ca(2+)-activated K+ channel was activated by a step increase in the intracellular Ca2+ concentration ([Ca2+]i) using the oil-gate concentration jump method in hippocampal neurons of rat. Limitations due to the unstirred volume between the excised inside-out membrane and the tip opening were examined. PMID- 1942669 TI - A microfluorometric method for simultaneous measurement of changes in cytosolic free calcium concentration and pH in single cardiac myocytes. AB - We describe a new system to measure changes in cytosolic free Ca concentration ([Ca2+]i) and pH (pHi) simultaneously using the dyes fura-2 and BCECF, and a random access camera with computer-operated synchronously-changing excitation and emission filters. Fluorescence intensities for fura-2 and BCECF were recorded from rat cardiac myocytes and calibrated in vivo using multiple-point determinations. [Ca2+]i and pHi were 88.6 +/- 32.8 nM and 7.16 +/- 0.12, respectively. PMID- 1942670 TI - [Formation of sexual identity among 9th grade girls]. AB - The present study was to explore the molding of sexual identity in early adolescent females. First, a questionnaire was administered to 168 9th grade girls. Out of all the respondents, 12 who did not have conflicts with sexual identity as an accepting group and 10 who had them as a non-accepting group were selected for the interview. Analyses of the results revealed that the contents of their conflicts cover various phases of femininity, which are concerned with body, character, and sex role etc. Moreover, it was found that not only their good images of parents, but also those of males were important when they achieve their sexual identity. PMID- 1942671 TI - [The development of the Japanese Irrational Belief Test]. AB - Japanese Irrational Belief Test (JIBT), a self-report type measure was developed as a means to aid the controlled clinical research on rational-emotive therapy. A five point scale questionnaire consisting of 107 items was administered to 211 Japanese university students, analyzed by factor analysis and item analysis, and seven scales of 10 items each were finally constructed. Seven scales measure the testee's beliefs on self expectation, problem avoidance, ethical blame, helplessness over inside, dependence, cooperativism and helplessness over outside. Coefficients of internal consistency of seven scales were 0.725 to 0.882. Both the JIBT and the STAI were administered to 208 normal subjects to examine their relationships, and the JIBT was also administered to 98 neurotic subjects to compare with the normal subjects. The results showed that for the normal subjects the beliefs on problem avoidance, helplessness over inside, dependence, cooperativism and helplessness over outside were highly correlated with anxious proneness, and statistically significant differences between the normal subjects and the neurotic subjects were found in the beliefs on self expectation, problem avoidance, helplessness over inside, dependence and helplessness over outside. PMID- 1942673 TI - [Direct priming]. AB - The purposes of this article are to review literature on direct priming (or repetition priming) and to comment on the current literature and its perspectives. Among a number of studies concerning direct priming, two categories of studies were mainly discussed: One is concerned with longevity of priming effects, and the other is concerned with variables which influence direct priming. Most of the former research has demonstrated long-lasting priming effects, but the theoretical account remains unclear. The latter has presented a variety of inconsistent findings. Finally three directions for future research were pointed out: methodological investigation, expanding research targets, and interaction among different approaches. PMID- 1942672 TI - [The strategy of decision makers in binary choices at the last phase of multi alternative decision process]. AB - The process of decision in a multi-alternative choice task is said to consist of two phases. In the first phase, undesirable alternatives are eliminated roughly on the basis of a few attributes. Then, in the second, the remaining alternatives are carefully evaluated and final choice is made. The purpose of this study was to determine how many alternatives survive the initial screening. Ninety students were asked to choose the best driving school from one of three sets, consisting of three, six, or nine alternatives. Subsequently, they were asked to recall the attributes of each alternative. In the "six" and "nine" alternative conditions, mean recalls for the third-ranking alternative was markedly lower than those of the top two alternatives. Moreover, the difference between mean recalls for the top two was very small. Within these multi-alternative conditions, the results suggested that two alternatives survived through the screening phase, and one of them was chosen in the last phase. PMID- 1942674 TI - [Effects of divided attention to visual and auditory stimuli on event-related potentials]. AB - Effects of cross-modal divided attention on event-related potentials (ERPs) were examined. Tone pips through either left or right headphones, and colored words, either red or blue on a CRT display were presented in random order with equal probabilities (.25). Each class of stimuli included rare target tones or words. Eight subjects were instructed to attend 1, 2, 3 or all of four classes of stimuli in various combinations and to press a button quickly when targets occurred in the attending classes. ERPs to non-target stimuli in each class were recorded. Attention-related negative components of ERPs were largest when attention was focused upon only 1 class of stimuli, and their amplitudes decreased when attention was divided. A greater attenuation of ERPs was caused by the intra- rather than inter-modally divided attentions. The results suggest that the attention-related negative components may reflect the limitation of capacity or interference among sub-mechanisms in each of visual and auditory modalities. PMID- 1942675 TI - [Construction of an arithmetic ability scale for grades three through five]. AB - To construct a scale for arithmetic ability, three forms of test were built and administered to grades three through five. Applying the two-parameter item response model, all parameters of the model were estimated simultaneously for three test forms. Thus, it was possible to compare the difficulty and the discriminating power of all items in a common scale. Accuracy of ability estimation of each test, which was evaluated by the test information function, revealed that precision of estimation was enough for practical use. In the common scale, the average of estimated ability was--.35 for grade three, 0.0 for grade four, and 1.48 for grade five, showing that the difference between grade three and four was small, compared to that between grade four and five. Possible applications of the scale were also discussed. PMID- 1942676 TI - [Mood congruent effects by music on word cognition]. AB - Two studies investigated the mood congruent effects of music on word cognition. In both studies, bright or sad music was used in order to induce elated or depressed mood, and subjects were assigned to either the bright or the sad music condition. In Study 1, positive and negative personality trait words and non words were presented with the music to examine the effect on incidental recall. Thirty-one subjects were asked to judge whether the words were positive or negative as quickly and accurately as possible. In Study 2, 37 subjects were presented with ambiguous personality trait words without and with music to examine how their interpretations of ambiguous stimuli were affected by music. The results showed the mood congruent effects on recall, interpretation, and response time, and these findings agreed with those obtained from other studies of the mood effects on cognition, especially on recall. It was suggested that music induces a certain mood, which influences on cognitive processes of other stimuli. PMID- 1942677 TI - [How people process increasing amounts of information as trials go on: reduction of the trade-off between memory and information-processing in the mental resources]. AB - In solving problems in which the amount of memory required increases during the course of solution the subjects would select such strategies as to cope with the deterioration of performance due to the trade-off between the memory load and the information-processing efficiency. To test the above hypothesis 58 graduates and undergraduates were asked to solve a number-guessing problem. In Experiment I, the subjects' responses were categorized and two different information-processing strategies were extracted; the condensation-of-information strategy and the partiality-decision strategy. These strategies were coded as flow charts. In Experiment II, to clarify the relation between processing and memory strategies, memory load was varied by giving the subjects different amount of cues for the solution. Results suggested that the subjects coped flexibly with the demand of situation by adaptive usage of two-layer solving strategies corresponding to the amount of memory load; one was a memory strategy and the other was a processing strategy. PMID- 1942678 TI - [Surgical management of valve replacement in children]. AB - From 1965 to 1990, 49 valve replacements were performed on 43 patients under the age of 15. Mitral valve replacements were performed on 21 patients, and re replacements were done on 4 of them afterwards. In the first 9 mitral valve replacements before 1974, Starr-Edwards (S-E) ball valves were used. Five of these patients died in the hospital (early mortality rate was 56%). Since 1975, bioprosthetic valves were used in three cases, but all of these valves ceased to function due to primary tissue failure (PTF) within 3 years. Consequently, SJM valves are now used as a first choice. Ten aortic valve replacements were performed on 9 patients with the results of one early death, two late deaths, and one late re-operation. Tricuspid valve replacements were performed on 11 patients, 5 of whom utilized S-E ball valves. Three of the five patients died in the hospital. One patient was re-operated on, swapping the S-E ball valve for the SJM valve. SJM valves were used primarily in 2 patients, and bioprosthetic valves in 4. Two patients died, one with a SJM valve, and the other with a bioprosthetic valve. Two pulmonary valve replacements were performed, one employing a SJM valve, the other a bioprosthetic valve. Two adult patients with SJM valve in the right side of the heart had thrombotic complications, though the patients with bioprosthetic valves had none. Atrioventricular valve replacements were performed on 5 patients under the age of 3, but all of them died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942679 TI - [Clinical application of total body retrograde perfusion to aortic dissection operation]. AB - Open distal anastomosis technique proposed by Cooley facilitates operative management of aortic dissection. Usually this procedure is performed under circulatory arrest, therefore, prolonged management is hazardous to cerebral and visceral organ systems. We have utilized profound hypothermia with total body retrograde perfusion: 1) myocardial protection through coronary sinus, 2) cerebral perfusion through superior vena cava with pretreatment of cerebral protective drugs, 3) abdominal visceral perfusion through inferior vena cava). We have obtained good results with this method in consecutive four patients with aortic dissection. PMID- 1942680 TI - [Postoperative percutaneous coronary angioplasty for stenosed aortocoronary vein bypass]. AB - This paper was presented to demonstrate the efficacy of postoperative PTCA for varying degree of stenosis aortocoronary bypass with saphenous vein grafts. The following conclusions were drown. 1. The success rate of postoperative PTCA for 15 grafts showed 88.8%. 2. The rate of success for PTCA was much more effective in patients within one year after bypass operations. The authors concluded that postoperative PTCA can be done with excellent rate of success. Therefore, postoperative cine-coronary angiography should be done to evaluate the state of the graft and to decide to perform possible postoperative PTCA in order to keep long time patency rate of saphenous vein grafts. PMID- 1942681 TI - [Significance of intraoperative measurement of secondary regurgitant tricuspid anulus]. AB - We evaluated the dilated tricuspid anuli (10 cases) during operation by means of direct measurement of the lengths of each leaflet anulus and compared with control group whose anuli were normal (12 cases). The lengths of anterior leaflet anulus and posterior one were dilated significantly more than control group. In this study tricuspid regurgitation was mainly proved to be the dilated anterior leaflet anulus. But it was not identified whether the dilatation of posterior one was contributed to the tricuspid regurgitation with the correlation of cardiac output and right atrial pressure from the underlying data. PMID- 1942683 TI - [Arterial graft anastomosis in coronary artery surgery: some technical points]. AB - To facilitate surgical technique, we describe some devices on arterial graft anastomosis in coronary artery surgery. Prior to anastomosis, the graft is positioned closely just parallel to the coronary artery by fixing surrounding endothoracic fascia or other connective tissues to the epicardium with 5-0 monofilament sutures. Stitching around the heel of the anastomosis is best performed by "a single stroke continuous suture" with the graft kept in position parallel to the coronary artery. This technique provides simple and secure anastomosis of an arterial graft. PMID- 1942682 TI - [A case of mediastinal mature teratoma with elevated of CA 19-9 in tumor fluid]. AB - A 20-year-old female was diagnosed as mediastinal tumor and admitted to our hospital for the operation. Among the preoperative examinations, the serum level of CA 19-9 was within normal limits. The fluid inside the cystic tumor which was removed during the operation showed high levels of CA 19-9. We discussed the relationship between CA 19-9 and cystic lesions. Histopathological study revealed that CA 19-9 was produced in only epithelial cell of the cystic lesion. And we speculated that examination of serum CA 19-9 helps the diagnosis of cystic lesions. PMID- 1942684 TI - [Lung transplantation in Washington University]. AB - Since the introduction of lung transplantation in 1983 by JD Cooper, the technical aspects of the procedure and the indication for lung transplantation have been refined and the success rate has steadily improved. He moved from Toronto to St. Louis in 1988 and established a new lung transplantation program in Washington University. The author had an opportunity to work with him for two years as a research fellow. The recent topics of lung transplantation in Washington University have been introduced and discussed. PMID- 1942685 TI - [CABG in 2 patients with severe left ventricular dysfunction]. AB - Coronary artery bypass grafting was performed in two patients with left ventricular dysfunction (EF 16%). In both cases they had chest pain at rest and ischemic myocardium were detected by the SPECT. We considered them candidate for the operation regardless of LV dysfunction. They were eventful in the postoperative course. One case was discharged and is free from chest pain now, but another unfortunately died for multiple organ failure. PMID- 1942686 TI - [Effect of intravenous administration of coagulation factor XIII concentrate on persistent pleural air leak]. AB - We administered coagulation factor XIII concentrate intravenously to six patients suffering from persistent air leak with no evidence of bronchopleural fistulae They are those who had either failed to be healed in response to pleurodesis, intrapleural fibrin glue injection and surgery or had not received such treatment. Their blood coagulation factor XIII activity levels were less than 70% of the standard plasma level. In four of the six patients, air leak stopped within 10 days after the treatment begun. Because factor XIII plays an important role in wound healing, reduction in the activity level can be a cause of insufficient healing of pulmonary surface fistulae and may lead to persistent air leak. In such cases, intravenous administration of factor XIII concentrate increases the activity levels and may put an end to persistent air leak. PMID- 1942687 TI - [Resection of metastatic pulmonary lesion of osteosarcoma extended into the left atrium and ventricle via the pulmonary vein]. AB - A 35-year-old woman had underwent an amputation of the right hemimandibula for an osteosarcoma. Twenty months after the operation, she was admitted to our hospital with complaints of syncope. On chest computed tomography and echocardiography, an atrial tumor was disclosed, which extended from the lesion of the left pulmonary lower lobe. This tumor intravascularly developed through the left inferior pulmonary vein. The intracardiac tumor was resected through left atriotomy under cardiopulmonary bypass, and immediately after weaning of bypass left lower lobe was resected. On pathological study the tumor was diagnosed as metastasis of osteosarcoma. Despite postoperative chemotherapy including CDDP, she died of metastasis in pulmonary, adrenal gland and liver 12 months after the second operation. PMID- 1942688 TI - [A case of ruptured aneurysm of Valsalva sinus into right atrium with peculiar findings on aortography]. AB - A 24-year-old man with ruptured aneurysm of sinus of Valsalva into the right atrium originating from the noncoronary sinus is presented. On aortography through the ascending aorta the right atrium in systolic phase and the right ventricle in diastolic phase were opacified. We considered ruptured aneurysm like a streamer (wind sock) entered into the right ventricle in diastolic phase and into the right atrium in systolic phase. Post-aneurysmectomy course was uneventful, and radiographic examination revealed complete repair of the aneurysm. PMID- 1942689 TI - [Coronary artery bypass surgery in dialysis patient]. AB - In patients with chronic renal failure undergoing hemodialysis for a long period, arteriosclerosis progresses rapidly, and the incidence of ischemic heart diseases is high. We performed coronary artery revascularization in a patient with chronic renal failure complicated by angina pectoris in whom discontinuation of dialysis was sometimes needed for hypotension during dialysis. Her postoperative course was uneventful. Problems in intra and postoperative management of dialysis patients are reported. PMID- 1942690 TI - [A case of open heart surgery associated with liver cirrhosis and pancytopenia]. AB - A 58-year-old female was diagnosed as mitral regurgitation and tricuspid regurgitation, combined with liver cirrhosis (T. Bil 2.3 mg/dl, ICG-R 37%) and pancytopenia (Hb 9.4 g/dl, WBC 3,000, Plt 56,000). She underwent mitral and tricuspid annular plications. After extracorporeal circulation, the postoperative platelet count was maintained higher than preoperative one by transfusion of platelet-rich plasma. Administration of FOY was begun during operation. Levels of T. Bil. and BUN were highest at 15th postoperative day and decreased gradually. Postoperative pleural effusion was treated by administration of 25% albumin solution keeping the level of Alb. up 3.5 mg/dl. PMID- 1942691 TI - [A successful surgical treatment of impending rupture of the thoracoabdominal aneurysm in the aged]. AB - In a case with impending rupture of the thoracoabdominal aneurysm of a 78-year old aged who was admitted to our hospital as chief complaints of dysphagia, sense of pressure in the thoracic region and bloody sputum, resection of the aneurysm and patch graft aortoplasty were carried out with the aid of partial cardiopulmonary bypass. The maximum diameter of the aneurysm was 12 cm, and adhered partially with lung, and a very thin ejected region of the wall was noted. Enlargement of the saccular aneurysm in the false lumen of the dissecting aortic aneurysm accompanying with massive mural thrombus was noted. The patch graft aortoplasty was performed because back bleeding from four sets of intercostal arteries (Th 9-Th 12) was remarkably noted. The postoperative course was uncomplicated, and dysphagia was disappeared without paraplegia. This case is considered to be the oldest one who was undergone the the thoracoabdominal aneurysm in our country. PMID- 1942692 TI - [Pleuropneumonectomy with combined resection of diaphragma, superior vena cava, and pericardium, for invasive thymoma with pleural dissemination]. AB - A 63-year-old female was admitted to our hospital with chief complaint of exertional dyspnea. Right massive pleural effusion was found. After chest drainage was performed, chest CT scan and MRI showed several masses in the anterior mediastinum and on the diaphragma. Mesothelioma was suspected for needle biopsy. Pleuropneumonectomy with combined resection of diaphragma, superior vena cava and pericardium was performed. Histologically, the Tumor was mixed thymoma. She is well and alive for three years after operation. Pleuropneumonectomy may be a choice of effective treatments for invasive thymoma with pleural dissemination. PMID- 1942693 TI - [A case report of perforated aneurysm of mitral valve with aortic regurgitation]. AB - The patient was a 71-year-old male who complained of palpitation and tachycardia. The echocardiogram showed a bulging of the anterior mitral valve leaflet toward the left atrium that persisted throughout cardiac cycle. The cine angiogram showed deformity of the anterior mitral valve leaflet with severe mitral regurgitation and mild aortic regurgitation. At operation, a perforated aneurysm was recognized at the anterior mitral valve leaflet without thrombus and vegetation. The size of aneurysm was 40 x 25 x 25 mm. The patient underwent MVR + AVR, and the postoperative course was uneventful. Pathological examination of the anterior mitral valve leaflet revealed scar-like fibrosis and old inflammatory change. It was judged a true aneurysm of mitral valve, because the structure of endocardium was kept. PMID- 1942694 TI - [A surgical experience of aortoventriculoplasty (Konno's procedure) for aortic stenosis associated with hypoplasia of aortic valve ring progressed after the repair of supravalvular aortic stenosis]. AB - A 14-year-old boy with aortic stenosis associated with hypoplasia of aortic valve ring underwent aortoventriculoplasty (Konno's procedure) successfully nine years after the repair of supravalvular aortic stenosis. His aortic annulus diameter before enlargement was 17 to 18 mm and after the procedure, a 25 mm St. Jude Medical prosthetic valve was implanted. It was adequate size for this large-sized student (173 cm in height, 67 kg in weight). After this operation, mild stenosis of right ventricular outflow tract was presented probably due to insufficient reconstruction of right ventricular outflow for such a dramatic enlargement of aortic annulus. Although this procedure makes possible to implant more than three size larger prosthetic valve without major complications, we have to be careful about preventing right ventricular outflow tract stenosis in case of requiring enlargement over 40 or 50% of aortic annular circle. PMID- 1942695 TI - [A case of dumbbell type extradural spinal meningioma]. AB - We reported a case of dumbbell type extradural spinal meningioma. The patient was a 45-year-old female. An abnormal shadow in the right middle lung field was pointed out in a mass survey. We recognized a dumbbell type tumor in the posterior mediastinum by chest CT and MRI. The tumor invaded the intervertebral canal through the spinal foramen. Operation was performed firstly with a longitudinal skin incision of the back and Th 6 laminectomy in a prone and secondly with a right posterolateral thoracotomy in a left lateral position. The dumbbell type tumor was completely removed by this operation. The pathological diagnosis was meningioma. The postoperative course was good. PMID- 1942696 TI - [A case report of emergency surgical repair of traumatic transection of thoracic descending aorta]. AB - The injury to the thoracic aorta caused by blunt chest trauma is often fatal. This case is 22-year-old male suffering from transection of the thoracic descending aorta caused by traffic accident. He was transported to our emergency room by an ambulance 15 minutes after the accident. Hundred fifty minutes after arrival to the hospital, we were rush to bring him to the operation theater suspecting serious injury of the thoracic organs in association with left hemothorax. The left standard thoracotomy disclosed the injury of the thoracic descending aorta. Simple cross clamp was applied to the thoracic descending aorta distal to the left subclavian artery for 20 minutes. Completely transected aorta was reapproximated using monofilament 3-0 polypropylene sutures with running manner. He tolerated the procedure well without any complication. His postoperative course was uneventful. He was followed up at the orthopedic department for associated hip fracture thereafter. PMID- 1942698 TI - [Urodynamics: current status and controversies]. PMID- 1942697 TI - [A case of Gunther vena caval filter insertion for recurrent pulmonary embolism]. AB - We report that the Gunther vena caval filter was successfully inserted in a case of recurrent pulmonary embolism resulting from ilio-femoral venous thrombosis. A 42-year-old woman was admitted to Osaka City University Medical School Hospital for dyspnea and chest pain on April 19, 1988. Pulmonary perfusion scintigraphy and pulmonary arterial angiography proved pulmonary emboli. The combination therapy of heparin and urokinase was performed, and her condition markedly improved. Then an ilio-femoral venography revealed only iliac vein compression but no thrombi. Therefore she was followed as an out patient with anticoagulant therapy. Nevertheless on April 10, 1989 she was admitted again complaining dyspnea and cyanosis. By venography at this time, some filling defects due to thrombi in right iliac vein were found. Therefore, we decided the insertion of the Gunther vena caval filter for recurrent pulmonary embolism using Seldinger method via right internal jugular vein. We expect that the Gunther vena caval filter will be useful for preventing pulmonary embolism resulting from ilio femoral venous thrombosis because its procedure is easy, non-invasive and without significant complications. PMID- 1942699 TI - [The anticancer effects of high energy shock waves on rat bladder cancer induced by BBN]. AB - The in vivo anticancer effects of high energy shock waves (HESW), on bladder cancer induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN), were studied in the rat using the Siemens lithotriptor (Lithostar). There was no significant difference in the anticancer effects in delaying tumor growth, measured as the whole bladder weight including the weight of the cancer, between the groups with and without exposure to HESW. However, light microscopic examination revealed extensive submucosal bleeding and exfoliation of mucosa, and electron microscopic examination revealed degeneration of pleomorphic microvilli, swelling of mitochondria, and destruction of mitochondrial cristae in the cancer cells in bladders exposed to HESW. Flow cytometric determination of DNA content in the cancer cells exposed to HESW indicated a selective diminution of cells in the G2 and M phases and an increase of cells in the G0 and G1 phases of the cell cycle. While the mechanism of HESW-induced anticancer effect could not be determined on the basis of this study, these changes in the morphology and the cell cycle of cancer cells induced by HESW exposure suggest some kind of biological effects following exposure to HESW. It is expected that HESW be an effective method for the treatment of human cancer in combination with chemotherapy and radiation. PMID- 1942700 TI - [The immunosuppressive effect of cholera toxin on rat renal allograft]. AB - Immunomodulatory effects of cholera toxin (CT) were investigated in a rat model, and the effects of CT on rat renal allograft (from Lewis rat to WKAH rat) were also examined. The results are: 1) The number of lymphocytes in the thymus, spleen and peripheral blood was remarkably decreased after 7 day administration of CT (0.1 and 0.2 mg/kg/day), but the number of red blood cells and neutrophils was not decreased. 2) CT suppressed mixed lymphocyte reaction (MLR) in a dose dependent fashion, and % suppression reached 97% at the concentration of 10 micrograms/ml. The later the time of addition of CT to MLR, the less became this effect. 3) In the control group, the mean survival time (MST) after transplantation was 8.5 +/- 0.3 (Mean +/- SE) days. CT, given 1 day before transplantation, did not prolong MST. In the group to which CT was given daily for 14 days from the day of transplantation, MST was prolonged with the increase of CT. CT at the dosage of 0.2 mg/kg/day prolonged MST (16.2 +/- 3.2 days) significantly (p less than 0.05), where treated with CT from the 3rd day after transplantation, MST (10.3 +/- 1.3 days) was not significantly prolonged. From the above findings, CT seems to act mainly on the early phase of acute rejection and prolongs rat renal allograft survival. PMID- 1942701 TI - [Prophylactic antibiotics after transurethral resection of prostate]. AB - We studied whether or not prophylactic use of antibiotics following transurethral resection of prostate (TUR-P) was needed. The subjects were 152 patients preoperatively passing sterile urine who underwent TUR-P. They were divided into three groups: 35 with no use of antibiotics (no prophylaxis group), 70 with one day use of antibiotics (one day-prophylaxis group) and 47 with use of antibiotics until pyuria disappeared (long term-group). The three groups did not differ in their rates of fever episodes (greater than or equal to 38.0 degrees C) during the first two weeks nor in the time of disappearance of pyuria. The no prophylaxis group and the one day-group differed statistically in their cumulative rates of bacteriuria (greater than 10(4) CFU/ml) on the postoperative third day: 4 patients (11.4%) in the no prophylaxis group and none in the one day group (p less than 0.01). On the 90th day, however, no significant difference was found in that rate: 22 patients (62.9%) in the no prophylaxis group and 32 patients (45.7%) in the one day group, 70% of the bacteria isolated from urine during the follow up were Gram positive cocci. The time to the elimination of pyuria was not influenced by the use of antibiotics. Our study suggests that postoperative antibiotics for patients passing sterile urine is not necessary following TUR-P. PMID- 1942702 TI - [Urinary cytology studied during 10 days after transurethral resection of bladder tumour and its relation to tumour recurrence]. AB - Whether or not recurrence is related to the results of urinary cytology examined within 10 days after transurethral resection of bladder tumour was studied retrospectively in 47 patients with superficial bladder tumour. Of 7 cases with positive cytology during the postoperative 10 day period, 4 cases had a later recurrence of tumour and 2 cases had a residual tumour due to incomplete resection of original tumour. By microscopic chromocystoscopy, in 11 patients concurrent urothelial atypia (carcinoma in situ or dysplasia) was found in the apparently normal mucosa. Nine of the 11 cases had a later recurrence of tumour or a residual tumour. Of in total 15 patients combined with abnormal cytology and concurrent urothelial atypia, 12 (80%) were found with recurrence of tumor cystoscopically 4 approximately 64 months (mean; 20.6 months) after TUR. This recurrence rate was significantly (p less than 0.05) higher than that (42.4%) in patients without positive cytology and concurrent urothelial atypia. These results suggest that positive urinary cytology during 10 days subsequent to TUR and/or association with concurrent urothelial atypia are indicative of later tumour recurrence, incomplete resection of tumour or presence of additional occult tumour foci. PMID- 1942703 TI - [Anti-bacterial defense mechanisms of the urinary tract constructed from intestinal segments. Studies on cell population and phagocytotic activity of urinary leucocytes, and bacterial growth in urine]. AB - Cell population of urinary leucocytes of 22 patients (intestine group) who underwent operations using intestinal segments for the urinary tract was compared with that of 26 complicated UTI patients without surgical intervention (control group). Eosinophils were recognized in 15.5 per cent of urinary leucocytes of the intestine group. However, in the control group, urine eosinophils were recognized only in 0.15 per cent. Although in sterile urines of the intestine group eosinophils were recognized in 30.8 per cent, in infected urines, the percentage of eosinophils decreased. Conversely, the percentage of neutrophils increased to 91.9 per cent. These findings suggest that neutrophils play an important role in infected urines of the intestine group as in urines of the control group. Significant differences were found in the values of urinary secretory IgA, IgG, IgM and urinary osmolarity. To evaluate the influence of these differences on the activity of phagocytosis of urinary leucocytes, the activity of phagocytosis of polymorphonuclear leucocytes (PMN), isolated from the peripheral blood, was investigated in immersion in urines of both groups. The mean rate of phagocytosis of E. coli in urines of both groups showed no statistically significant differences. However, urinary osmolarity of the intestine group was within the suitable range for phagocytosis and the activity of phagocytosis in urine was correlated with the value of IgG, which suggests that IgG has the opsonic effect. In contrast, the activity of phagocytosis in urine of the control group was strongly correlated with the value of urinary osmolarity. The growth of Providencia, Streptococcus, P. aeruginosa, whose frequency of isolation from urine of both groups was different in our previous study, and E. coli was studied in urine of the two groups. No significant difference in the growth of all bacteria was found, however. This finding suggests that the difference in the frequency of isolation of these bacteria from urine possibly depends on the adhesion of bacteria to intestinal epithelium. PMID- 1942704 TI - [Analysis of frequency volume chart in elderly people with pollakisuria. Comparison between the elderly and the adult]. AB - Based on the frequency volume chart, 215 patients who complained of pollakisuria were clinically investigated. The subjects were divided into 2 groups: the elderly group was composed of 85 patients more than 65 years of age (mean of 72) and the adult group comprised 130 patients less than 64 years old (mean of 47). The elderly group was characterized by the fact that, during nighttime (after sleep), their urinary volume was larger, each voided volume was smaller and the number of voiding was greater than the other group. Clinical analysis of the causes of pollakisuria enabled us to subdivide them into 6 diagnostic categories. Among the elderly patients polyuria during sleep and unstable bladder were prevalent and among adult patients unstable bladder and over hydration were common. Medication was made in 80 patients (37%), while 108 (50%) needed neither medication nor surgery. It is stressed that the frequency volume chart is one of the important diagnostic tools to evaluate the cause of pollakisuria and to select appropriate treatment. PMID- 1942706 TI - [A model of orthotopic transplantation in mice using MBT-2]. AB - We attempted to produce a malignant urinary bladder carcinoma in mice by transplanting MBT-2 cells. MBT-2 carcinoma about 3.0 x 10(3) cells/0.02 ml were successfully transplanted into the bladder wall with an incidence of 80% (20/25) after three experimental weeks. Inoculated tumor cells grew expansively into the bladder cavity from the bladder submucosa, and invaded the muscle layer. We observed that tumors caused gross hematuria and bilateral hydronephrosis. This malignant tumor model in which a tumor is implanted into its original organs seems to be useful for predicting clinical effectiveness in experimental cancer therapy. PMID- 1942705 TI - [A clinico-pathological study of 69 cases after total cystectomy]. AB - A clinico-pathological study was conducted on 69 patients with bladder cancer who underwent total cystectomy. The one, three and five-year actuarial survival rates for the 69 patients were 73.3%, 48.6% and 44.1%, respectively. Survival rate was not significantly associated with sex, the number of tumors or the size of tumors. The survival rate in those aged 70 years or more was slightly worse than in those who were much younger. Patients with papillary tumors had a more favorable survival rate than those with non-papillary tumors but we could find no significant difference between those with pedunculated tumors and those with sessile tumors. The actuarial 5-year survival rates by grade were 71.9% in G1 + G2, 22.6% in G3 and 32% in non-transitional cell carcinoma; the rates by stage were 86.5% in pTa + pT1, 85.7% in pT2, 20.8% in pT3a, 18.2% in pT3b and 0% in pT4. When the stage reached pT3a, the survival rate fell remarkably. The rate of INF alpha (93.8%) was significantly better than that of INF beta (28.1%) and INF gamma (15.2%). The rate of ly0 (76.2%) was also significantly better than that of ly1 (25.5%) and ly2 (18.8%). There was no significant difference in survival between v(-) (50.7%) and v(+) (25.9%). We could find no significant difference between patients who underwent pelvic lymph nodes dissection and those who did not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942707 TI - [Clinical study of extracorporeal shock wave lithotripsy for stones in solitary kidney]. AB - Extracorporeal shock wave lithotripsy (ESWL) treatment was performed on 17 patients with a solitary or sole functioning kidney from August 1986 to April 1988. Some patients with renal stone had a double pig tail catheter to protect the stone street and those with ureteral stones had a ureteral balloon occlusion catheter to raise the efficiency of fragmentation placed prior to ESWL as much as possible. Combined manipulation with such an instrument as nephrostomy tube to wash out residual stone fragments or endoscopic operation were performed. Despite of these devices, ESWL treatments for staghorn calculi and cystine stones were troublesome in solitary kidneys. After follow up ranged from 9 to 602 days (mean 87.6 days), 10 patients (58.8%) were stone free. ESWL treatment is safe and effective for solitary kidneys. We recommended premedication and pretreatment by ureteral stenting in patients with a solitary kidney. PMID- 1942708 TI - [Application of the nucleolar organizer regions to urinary cytology and its computer-assisted image analysis]. AB - Quantification of argyrophilic nucleolar organizer regions (AgNORs) stained by the silver colloid method in urinary exfoliative cells from 36 benign urological diseases and 33 transitional cell carcinomas (TCC) of the urinary bladder was carried out. Also, AgNORs of these cells were measured by means of the computer assisted image analysis system. There was a significant correlation between AgNORs numbers of cells from voided or wash-out smears and those from touch smears (p less than 0.01). The mean AgNOR numbers per nucleus showed a stepwise increase from non-infected benign urological diseases (mean +/- SD: 3.33 +/- 0.60) through infected urological diseases (3.88 +/- 0.58), grade 1 of TCC (5.23 +/- 1.39) and grade 2 of TCC (6.34 +/- 0.86), to grade 3 of TCC (8.09 +/- 1.19). The maximum number of AgNORs in each group indicated almost the same results. The estimation of the distribution of the maximum AgNOR number might be of great value for rapid and reliable detection of bladder cancers. Moreover, the computer assisted image analysis of AgNORs could offer an objective index for the cytological assessment of urinary bladder diseases including TCC. PMID- 1942711 TI - Mind reading for the 90s. PMID- 1942709 TI - [Ewing's sarcoma in the retroperitoneum]. AB - The patient was a female aged 18. Hematuria was discovered at an examination two years previously at which time the patient was complaining of right lumbar pain. The patient visited our hospital with a chief complaint of right abdominal tumor in June, 1988. A retroperitoneal tumor, 77 X 45 mm in size, was observed by CT and ultrasonic examination, and the right kidney was in hydronephrosis. An operation was performed in September, 1988, based on a diagnosis of retroperitoneal tumor and hydronephrosis. The tumor was seen to have involved the right ureter. Subsequently the tumor was surgically removed; right total nephroureterectomy and partial cystectomy were performed at that time. The removed tumor was 90 X 70 mm in size and 120 g in weight; it was histopathologically diagnosed as extraskeletal Ewing sarcoma. A systemic examination was carried out postoperatively, but no abnormalities were observed. As of September, 1990, the patient had had no recurrence and was being kept observation on an outpatient basis. There have been a total of 210 case reports regarding extraskeletal Ewing sarcoma published worldwide, including our case and 26 cases in Japan, so far as we know. However those of a lesion of retroperitoneal origin are extremely rare, numbering only 11 cases worldwide and 2 Japan. Herein we report our case of extraskeletal Ewing sarcoma with reference to the other 209 cases reported in the literature to date. PMID- 1942710 TI - [Two case reports of eosinophilic cystitis--clinical review of 43 cases in Japan]. AB - Two cases of eosinophilic cystitis are reported. Case 1 was a 7-year-old boy with pollakisuria and case 2 was a 20-year-old man with right lower abdominal pain. They were suspected of bladder sarcoma after the examinations by cystoscopy, IVP, ultrasonography, CT and NMR-CT. Transurethral, percutaneous and open biopsies were performed and histological examination revealed massive infiltration of eosinophils mainly in the vesical muscle layer without malignant cells. We could establish the diagnosis only by biopsy. In case 1, IgE RAST was positive for tick and case 2 seemed to be allergic to rare beef. We presumed that they caused eosinophilic cystitis. PMID- 1942712 TI - To arms, to arms. PMID- 1942713 TI - Two new decisions on two old concepts. PMID- 1942714 TI - Reducing vaccination barriers in Kansas. PMID- 1942716 TI - Sensitivity and specificity of thallium stress testing. PMID- 1942715 TI - Carotid endarterectomy: immediate morbidity and mortality in 337 patients. PMID- 1942717 TI - AMA adopts new position on AIDS. PMID- 1942718 TI - Suffer, the little children. PMID- 1942719 TI - Factors influencing the survival of patients with cervical carcinoma. PMID- 1942720 TI - Physician to rancher (and back again). Part one. PMID- 1942721 TI - Limitations of the traditional evaluation of congestive heart failure. PMID- 1942722 TI - [Reactivities of various mycobacteria species against DNA probes (Gen-Probe Rapid Diagnostic System) specific to Mycobacterium tuberculosis complex, Mycobacterium avium and Mycobacterium intracellulare]. AB - Various mycobacterial species (22 species, 178 strains) were studied for their reactivity to DNA probe specific for Mycobacterium tuberculosis complex (MTC), M. avium or M. intracellulare, using Gen-Probe Rapid Diagnostic System (Gen-Probe Inc., San Diego, Calif., U.S.A.). All the MTC strains, including M. tuberculosis, M. africanum, M. bovis and M. microti reacted with MTC-DNA probe at the % hybridization value of 42.8-51.9% (values higher than 10% are regarded as positive), but their reactivity to MAC-DNA probes (0.8-2.5%) was under the cut off value (10%). The test strains (28 strains) of M. avium complex (MAC) segregated into two groups on the basis of reactivity to DNA probes specific for M. avium and M. intracellulare, that is, one group (16 strains) positively reacted with M. avium-probe but not with M. intracellulare-probe, and the other group (12 strains) showed the converse reactivity. The two groups did not show a reactivity with MTC-probe higher than the cut off value. Nontuberculous mycobacteria other than MAC, including M. kansasii, M. marinum, M. simiae, M. asiaticum, M. scrofulaceum, M. gordonae, M. szulgai, M. malmoense, M. xenopi, M. gastri, M. nonchromogenicum, M. terrae, M. triviale, M. fortuitum, and M. chelonae (subsp. abscessus and chelonae) reacted with neither MTC- nor MAC-probe and values for % hybridization (0.6-3.6%) were lower than the cut off value. These findings indicate extremely superior specificity of the DNA probes (Gen Probe) for MTC, M. avium and M. intracellulare, thereby indicating the usefulness of Gen-Probe Rapid Diagnostic System for the MTC and MAC in clinical use. PMID- 1942723 TI - [Study on the pulmonary tuberculosis in the elderly]. AB - A study was made for 13 cases of patients over 80 years of age who received medical treatment for tuberculosis. Four factors of onset of tuberculosis at old age were indicated. 1. No opportunity for examination of X-ray for old generation. 2. Atypical shadows on the chest X-ray film. 3. Low stress tolerance. 4. Exacerbation of old tuberculosis during the treatment of other diseases. The results suggest the possibility of increasing pulmonary tuberculosis among the elderly persons in the near future. PMID- 1942724 TI - [Macrophage respiratory burst-inducing activity of Mycobacterium fortuitum: relationship with its virulence to mice]. AB - Mycobacterium fortuitum strains F-3 and 126 were studied for their virulence to mice, by being given intravenously to BALB/c strain mice, in terms of incidence of spinning disease, degree of gross renal lesions and growth of organisms in kidneys. In three experiments separately carried out, strain 126 showed considerably higher virulence than strain F-3. In particular, in experiment 2, much higher incidence of spinning disease was seen in strain 126- infected mice than in strain F-3-infected ones. In experiment 3, the degree of gross renal lesions was significantly higher (P less than 0.025, chi 2-test) in the strain 126-infected animals than in the F-3-infected ones. Moreover, in experiment 2, the number of viable units in kidneys was significantly larger in the case of strain 126-induced infection than in the case of strain F-3-induced one (P less than 0.01, Student's t-test). Secondly the two M. fortuitum strains were studied for their activity to trigger chemiluminescence (a parameter for respiratory burst) of murine peritoneal macrophages, due to their contact with macrophages. In two of four experiments separately performed, strain 126 exhibited much lower activity of macrophage chemiluminescence-triggering than strain F-3. In the remaining two experiments, the triggering activities of the two strains were at almost the same level, although the activity of strain 126 was still somewhat lower than that of strain F-3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942725 TI - [A case of tuberculous lymphadenitis diagnosed by the open abdominal lymph node biopsy]. AB - A 16-year-old female was admitted to our hospital six months ago. On X-ray examination of the test, swelling of lymph nodes in the right mediastinum was seen. CT scan showed multiple lymph node swelling in the neck, mediastinum and abdomen. On open abdominal lymph node biopsy, she was diagnosed as tuberculous lymphadenitis and liver tuberculosis. Antituberculous chemotherapy consisting of INH, RFP, EB and SM was started. After regular treatment, right mediastinal lymph nodes were markedly reduced in size on chest X-ray film. At present, she is in fine condition. Surprisingly, her condition has improved to a great extent within six months. PMID- 1942726 TI - [In vitro activities of newly developed quinolones, fleroxacin, lomefloxacin and sparfloxacin against Mycobacterium tuberculosis]. AB - In vitro antituberculous activities of three newly developed quinolones, fleroxacin (FLRX, AM-833), lomefloxacin (LFLX) and sparfloxacin (SPFX, AT-4140) were evaluated in comparison to that of ofloxacin (OFLX) using M. tuberculosis strains isolated from patients and the Ogawa egg medium. SPFX was apparently more active than OFLX, but both FLRX and LFLX were less active. SPFX inhibited completely the growth of all 20 strains of M. tuberculosis isolated from patients who were not previously treated with OFLX in a concentration of 1.25 micrograms/ml. However, this agent inhibited the growth of only 4 strains (28.6%) of 14 OFLX-resistant M. tuberculosis in a concentration of 1.25 micrograms/ml, suggesting a partial cross-resistance between SPFX and OFLX. PMID- 1942727 TI - Clinical features, diagnoses, and management of tuberculosis in immunocompromised hosts. AB - For many years tuberculosis has been known to occur with greater frequency among persons with disorders that impair host defenses. In most instances these processes interfere with the immune response to Mycobacterium tuberculosis, whereas, in a few, such as silicosis, the probable abnormality is a nonimmune defect in macrophage function. Infection with the human immunodeficiency virus (HIV) causes progressive and ultimately profound depression of both humoral and cell-mediated immunity and, thus, is an extremely potent risk-factor for tuberculosis. Presumably the major effect of HIV infection that predisposes persons to developing tuberculosis is the reduction in circulating T-helper (CD4+) lymphocytes which causes a reduction in cytokine production and a consequent decrease in the functional capabilities of macrophages. However, a number of questions concerning pathogenesis of tuberculosis related to HIV remain. Available data suggest that the magnitude of the risk for developing tuberculosis among persons infected with both HIV and M. tuberculosis is very high, 8% in one prospective study. Because of the epidemic of HIV infection, the progressive downward trend in the incidence of tuberculosis in the United States has reversed and in 1989 there was a 5% increase in the number of cases. Preliminary data for 1990 suggest that there will be an 8 to 10% increase over 1989. Also in the United States approximately 3% of tuberculosis patients have been found to be HIV seropositive. The clinical features of tuberculosis in patients with HIV infection vary depending on the degree of immunosuppression. With mild immunosuppression early in the course of HIV infection tuberculosis presents in a "typical" way with positive tuberculin skin tests, upper lobe cavitary infiltrates on chest film and positive sputum smears and cultures. As the HIV infection progresses, the mode of presentation of tuberculosis becomes more "atypical" with negative skin tests, multiple sites of involvement, chest films showing diffuse noncavitary infiltrates often accompanied by intrathoracic lymphadenopathy. The key to diagnosis is maintaining a high index of suspicion for tuberculosis, especially in patients with advanced HIV disease and including appropriate laboratory examinations in the evaluations of such persons. Regardless of the stage of HIV infection the response to treatment for tuberculosis is generally favorable if it is begun promptly. Standard therapy utilizing isoniazid, rifampin, and pyrazinamide with or without ethambutol have been associated with high rates of cure. Relapse has been uncommon. There has been, however, at least one outbreak of tuberculosis caused by isoniazid and rifampin resistant organisms in which the response to therapy was very poor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1942728 TI - [Adoptive immunotherapy for pulmonary tuberculosis caused by multi-resistant bacteria using autologous peripheral blood leucocytes sensitized with killed Mycobacterium tuberculosis bacteria]. AB - A patient with pulmonary tuberculosis caused by bacteria resistant to various anti-microbial agents was treated with adoptively transferred autologous peripheral blood leucocytes (PBL) sensitized with killed Mycobacterium tuberculosis organisms in vitro. The 32-year-old man was admitted to our hospital from National Sanitarium Okinawa Hospital with weight loss, high fever, and rapid aggravation on chest X-ray. Patient's PBL obtained by leukapheresis and separated with Ficoll-Hypaque solution were cultured with killed Mycobacterium tuberculosis bacteria of 0.4 microgram per ml at 1 x 10(6) cells per ml for 7 days in media containing 0.5 U recombinant 1L-2 per ml. After incubation, PBL were layered and centrifuged on Ficoll-Hypaque solution and washed three times with saline. PBL (1 3 x 10(8)) were combined and concentrated for infusion in 20 to 30 ml saline. After injection, patient displayed fever and transitory drop of PaO2. Although the patient did not have an improved on chest X-ray, his fever was alleviated, weight was increased, accelerated ESR was slightly improved, and the number of organisms in sputum (Number of Gaffky) temporarily decreased. Adoptive immunotherapy using the autologous PBL which were sensitized with killed bacteria may be an effective anti-tuberculous immunotherapy. PMID- 1942729 TI - [Preventable tuberculosis cases in Japan--a new approach to the assessment of tuberculosis control problems]. AB - I defined cases of tuberculosis which could not be prevented from infection or development of disease among infected, or could not be detected in the early stages as "preventable cases" in order to evaluate tuberculosis control efforts in the community, Japan. Among 241 bacteriologically confirmed cases with pulmonary tuberculosis newly registered from 1988 through 1989 in Yamagata Prefecture, 80 (33%) were defined as preventable cases by observing their course and the process of diagnosis. That is to say, one-third of bacillary cases could have been prevented in Yamagata where the incidence of tuberculosis was lowest in Japan, if existing prevention and control methods had been effectively used. Causes of prevention failure were investigated in detail. The most common cause was tardy detection of cases, especially due to delayed confirmation of diagnosis (so called "doctor's delay"). The delayed confirmation of diagnosis resulted from neglecting chest X-ray and sputum examination and from ignoring high risk groups. In the younger age group, it was mainly attributed to insufficient family contact examinations. Tuberculin skin tests are necessary not only for those aged 15 years and younger but also for those aged 16-29, when they are found to be household contacts of smear-positive cases. An evaluation of tuberculosis control program defining preventable cases would be a beneficial approach to the surveillance of tuberculosis. PMID- 1942730 TI - [Analysis of cellular and biochemical contents of broncho-alveolar lavage fluid from patients with pulmonary tuberculosis]. AB - To evaluate the local immune response in lung and activity of pulmonary tuberculosis. Broncho-alveolar lavage (BAL) was performed on 15 patients with pulmonary tuberculosis. Patients consisted of nine in the active stage and six in the inactive stage. Acid-fast bacilli (AFB) in BAL fluid (BALF) were found in six out of nine active stage patients (BAL-AFB positive group). The results obtained were as follows; 1) The number of total cells in BALF increased significantly in BAL-AFB positive group. BALF from two patients of this group, who were in the very early stage, revealed that the lymphocytes increased predominantly whereas neutrophils were dominant in BALF from the other four patients. 2) No case showed increase of B cells in BALF. Lymphocytes surface markers were compared between BAL-AFB positive and negative groups. No difference was found in the numbers of OKT3, OKT4 and OKT8. The positive rates of OKIal, and OKT4/8 ratio were both increased in BALF compared to the BAL-AFB positive group. 3) The numbers of OKT4 and OKT4/8 ratio in peripheral blood, which were taken simultaneously with BAL, were decreased in patients in the active stage. 4) Protein, albumin, IgG, IgA, lysozyme and alpha 1-antitrypsin levels in BALF were all increased in tuberculous patients. No correlation between the activity of tuberculosis and levels of protein, albumin, IgG and IgA was observed. Lysozyme level increased in the inactive stage of patients. On the other hand alpha 1-antitrypsin level increased in the active stage. Fibronectin level in BALF from patients was lower than that from normal controls. 5) Smoking habit had no influence on the above results. 6) Only one case showed the appearance of new lesions after BAL procedure as a complication. PMID- 1942731 TI - [Clinical studies on lung disease due to atypical mycobacteria in our hospital during the past 13 years]. AB - Among the patients with pulmonary diseases admitted to our hospital during a 13 year period from 1977 to 1989, clinical examinations and laboratory data on admission and the following clinical courses of 102 cases where atypical mycobacteria had been identified three times or more in sputum cultures at the time of hospitalization were investigated. 1. The ratio of the number of cases positive for atypical mycobacteria to those positive for acidfast bacilli in sputum cultures tested on admission was fairly constant, 6.0 to 7.8% every year since 1981. In the cases associated with positive sputum cultures for atypical mycobacteria, M. avium complex was observed in 84% of the cases: M. kansasii, M. fortuitum and M. chelonae were found in 13, 2 and 1 cases, respectively, since 1984. 2. A total of 102 cases studied consisted of 66 male and 36 female patients; the mean age was 61.9 years. 3. Sputa became negative on culture in 19 (86.4%) out of 22 cases of primary infection. In all primary infection cases, roentgenographic findings did not worsen and prognosis was extremely good. In secondary infection cases, sputum cultures became negative in 25 (83.3%) out of 30 cases expectorating a small quantity of mycobacteria on admission, where x-ray findings worsened in only one case. In contrast, in 47 cases expectorating a large quantity of the bacilli at the time of admission, negative sputum cultures were attained in only 14 cases (29.8%) and x-ray findings worsened in 10 cases, and their prognosis were poor. 4. In general, sputum cultures turned negative within 3 months after admission. If sputum cultures remained positive thereafter, it was found very difficult to stop expectoration of the bacilli in these patients, and hence their prognosis are supposed to be greatly affected by the bacteriologic findings in early stages of the disease. PMID- 1942732 TI - [Establishment of a host-vector system in Mycobacterium bovis BCG]. AB - The recombinant plasmids, pYT72 and pYT92, were generated from a mycobacterial plasmid, pMSC262, and a Escherichia coli plasmid, pACYC177. These plasmids were capable of replication, and of stable maintainance in Mycobacterium bovis BCG when introduced by electroporation technique. Efficiency of transformation was about 10(4) transformants/micrograms DNA, and was the highest in the phage sensitive mutants (S-10, S-20) isolated from BCG Tokyo strain. We have also isolated transformable mutants from rapidly growing bacterium, M. smegmatis strains Jucho and TMC1533. By isolating deletion mutants from pYT72/92, we could determine the location of replication region of pMSC262 within a 2.3 kb Pst I Hind III fragment. Using this fragment, we constructed "mini" shuttle plasmid pYT937 (5.9 kb in size) which possesses kanamycin and ampicillin resistance markers and replicates in both E. coli and Mycobacterium. Nucleotide sequence analysis of the replication region revealed that there are 2 potential coding regions which contain more than 200 amino acids. The largest one (ORF1) which codes 311 amino acids, however, lacks Shine-Dalgarno like sequence in the upstream and therefore may not be functional. The other coding region (ORF2) contains 260 amino acids and was preceded by Shine-Dalgarno like sequence. Upstream of the ORF2, there were several repeat sequences which may be important in the plasmid replication. GC content of the 2.3 kb fragment was 69.8%. PMID- 1942733 TI - [Study on recombinant BCG]. AB - For the purpose to establish the system to express foreign antigen from Mycobacterium bovis BCG. We have cloned, sequenced and expressed genes for secreting proteins, alpha antigen, MPB64, MPB57 and MPB70 from M. bovis BCG. The upstreams and structural genes were characterized. The gene for alpha antigen of Mycobacterium kansasii was also characterized. The gene for alpha antigen of M. kansasii (k-alpha) was chosen for the further study at first. This gene was fused with shuttle plasmid PIJ666-PAL5000 obtained from T. Kisser and transfected to M. bovis BCG (Tokyo). Transformant was obtained by a selection with kanamycin. It was able to secrete k-alpha antigen. DNA-containing a B-cell epitope (Glu-12-Leu Asp-Arg-Trp-Glu-Lys-Ile-19) of human immunodeficiency virus type 1 P17 gag was fused to this vector at C terminal of k-alpha. Using this vector, we have succeeded to express foreign antigen in M. bovis BCG. The products were analyzed in one or two dimensional electro-phoresis. The results thus obtained will be reported elsewhere. PMID- 1942734 TI - [Genetic engineering of cytokine system on the tuberculosis research]. AB - Murine IL-5 is an acidic glycoprotein with a molecular mass of 40 to 50 kda that consists of homodimer of which monomer comprises 113 amino acid residues. Murine IL-5 has pleiotropic activities on various target cells. IL-5 acts on committed B cells to induce differentiation into Ig-producing cells and on common progenitors for Ly-1+ pre-B cells and Ly-1+ macrophages to support their growth. It also supports growth and/or differentiation of eosinophil precursor and mature eosinophil. IL-5 specifically binds to its receptor (IL-5R) with high and low affinity. IL-5 signals appears to be transduced through the high affinity IL-5R that is composed of two different polypeptide chains; alpha chain and beta chain. The IL-5R alpha chain cDNA encodes p60 that binds IL-5 with low affinity. The IL 5R beta chain, p130/p140 does not bind IL-5 by itself, but binds to alpha chain/IL-5 complex to convert them to the high affinity IL-5R. The beta chain was identified as the IL-3R homologue, AIC2B. Both alpha and beta chain of IL-5R belong to a cytokine receptor superfamily. PMID- 1942735 TI - [Mycobacterium examination system at the National Jewish Center in the States]. AB - Impressions on visit to Mycobacteriology Laboratory of National Jewish Center for Immunology and Respiratory Medicine are reported. The BACTEC and Gen-Probe Method are introduced to the laboratory system on mycobacterial examinations such as detection, identification, drug susceptibility and minimal inhibitory concentration test. PMID- 1942736 TI - House Bill No. 2531 passes community based reduction of teenage pregnancy programs. PMID- 1942737 TI - Homelessness in America's heartland: health perceptions of the homeless. Part 1. PMID- 1942738 TI - We hereby resolve to save the planet. Resolution 90-4: global warming. PMID- 1942739 TI - Nursing directed health care with the homeless population. PMID- 1942740 TI - Affects of 1990 Kansas legislation. Deinstitutionalization--of the chronic mentally ill in kansas. PMID- 1942741 TI - The Galena project: nursings' contribution. PMID- 1942743 TI - The Kansas EACH project. PMID- 1942742 TI - Characteristics and health needs of homeless persons in and urban agency. Part 2. PMID- 1942744 TI - [The importance of the autonomic nervous system for sinus and atrioventricular node function in patients with sick sinus syndrome]. AB - Autonomous nervous system (ANS) influence on sinus (SN) and atrioventricular (A-V N) nodes is still under investigation, especially in pathological states. We analysed role of ANS for SN and A-VN function in patients with different forms of sick sinus syndrome (SSS). From 310 patients (pts) after electrophysiological examinations before and after pharmacological denervation of the heart we selected 206 pts with SSS (group S) for further investigation. In group S were 124 men and 82 women from 17 years old (mean 46 +/- 16). Coronary heart disease was present in 102 pts (myocardial infarction in 7), mitral valve prolapse in 10, hypertrophic cardiomyopathy in 2. SSS was the only pathological finding in 75 pts. In 92 cases pacemaker was implanted (45%) of whole group S. Only sinus bradycardia was observed in 118 cases, tachycardia-bradycardia syndrome in 34 and sinus arrest or/and sinoatrial block in 53 cases. Electrophysiological examinations were performed using transesophageal stimulation of the left atrium before and after denervation of the heart. Pharmacological denervation of the heart was obtained by propranolol (i.v. 0.2 mg/kg body weight) and than atropine (i.v. 0.04 mg/kg body weight). We analysed sinus cycle length in basic state, after propranolol injection and after full denervation, maximal sinus nodes recovery time, maximal corrected sinus node recovery time, secondary pause, sino atrial conduction time, Wenckebach point before and after full denervation. The whole group with SSS (group S) was divided: pts with normal (S1) and abnormal (S2) intrinsic properties of SN (104 and 102 pts respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942745 TI - [Clinical evaluation of incomplete PTCA revascularization efficacy]. AB - Long term results of incomplete PTCA revascularization (IR) were estimated in 89 patients (P) with multivessel disease (MVD). P were divided into four groups according to severity and localization of stenoses on coronary angiography. Type A (n = 23): two or more stenoses greater than or equal to 70%, one of which localized in proximal segment was dilated, others in peripheral segments of major epicardial vessels or their branches were left. Type B (n = 30): stenosis greater than or equal to 70% in proximal part of one artery was dilated, other moderate stenoses 50-70% were left. Type C (n = 26): one coronary artery occluded, second vessel with stenosis greater than or equal to 70% was dilated. Type D (n = 10): one or two coronary arteries occluded, in two or three others stenosis 70%, vessel crucial for collateral flow was dilated. On follow-up (x 17.7 months), 57 (64.1%) P were completely free of angina, 23 (25.8%) had only mild effort angina with good response to NTG. Only 9 (10.1%) P required coronary bypass surgery, 6 of them with type D MVD. CONCLUSIONS: 1. IR gives satisfactory long term results in P with type A, B, C of MVD; 2. IR is a palliative procedure in high risk surgical P with type D of MVD, but in some cases gives good clinical results. PMID- 1942746 TI - [Essential hypertension. Treatment with nifedipine and levels of insulin, glucagon, gastrin and prolactin]. AB - In 40 patients (pts) with essential hypertension (EH) the plasma levels of insulin, glucagon, gastrin and prolactin during 2 week therapy with nifedipine were evaluated. In pts with EH there were higher levels of hormones than in control subjects. During nifedipine therapy there was no elevation of the plasma hormone levels although the blood pressure was lowered. This study shows that there are other than hypertension factors in the pathogenesis of elevated hormone levels in EH. PMID- 1942747 TI - [Recurrent episodes of Morgagni-Adams-Stokes syndrome due to degeneration of atrio-ventricular tachycardias into atrial fibrillation in a patient with Wolf Parkinson-White syndrome]. AB - We present clinical problems and the therapy of a 52 year old patient with Wolf Parkinson-White syndrome and numerous episodes of Morgagni-Adams-Stokes syndrome. In that patient atrio-ventricular tachycardia caused atrial fibrillation. Short refractory period of the accessory pathway and the ventricular muscle allowed for extremely fast ventricular rate with haemodynamic collapse and syncope. Long-term treatment with propafenone or amiodarone did not prevent the arrhythmias. Electrophysiological study pre- and intraoperation including the epicardial mapping were performed several weeks after discontinuation of therapy with amiodarone. The studies revealed left free wall accessory pathway. Dr. A. Biederman and al. performed dissection of the accessory pathway. There were no evidence of conduction through the accessory pathway during the post operation electrophysiologic study. The patient has neither reentrant tachycardias nor atrial fibrillation episodes. PMID- 1942748 TI - [Unusually large vegetation on the mitral valve in a patient with bacterial endocarditis]. AB - We present a case history of 29-year old female with infective endocarditis, who was admitted 15 months after neurosurgical treatment of disruption of cerebral aneurysm. The diagnosis of organic heart disease had been established in her childhood. 6 months after discharge from neurosurgery she developed marked dyspnoea on exertion and became febrile (up to 39.0 C). The presumptive diagnosis of infective endocarditis was established 6 months later, when she developed the symptoms and signs of severe anaemia with ESR 170 mm/hr although blood cultures were negative. The patient underwent treatment with Penicillin and Debecillin. On admission to our Institute echocardiography showed a very large, mobile vegetation in the left ventricle, connected to the anterior leaflet of mitral valve. Decision of mitral valve replacement was made, but rupture of the next cerebral aneurysm was the reason of unexpected, sudden death of the patient. The postmortem examination revealed 7 x 4 cm large vegetation, with the mass of 7.0 g. Histologically the vegetation consisted of mass of fibrin strands, platelets and blood cell with inflammatory cells. On its base the signs of the process of organization were marked. This vegetation was the largest one that we found in literature on this subject. PMID- 1942749 TI - [Contemporary directions in the treatment of hypertension]. PMID- 1942750 TI - [Intensity of tone and opening snap, and morphology of the bicuspid valve in patients with mitral valve disease]. AB - The purpose of this study was to investigate the correlation between mitral valve morphology and amplitude of the first heart sound and the opening snap. The material consisted of 21 women and 19 men with mitral valve disease. They ranged in age from 24 to 56 years. 36 patients had pure or dominant mitral stenosis and 4 patients had combined mitral valve disease with dominant regurgitation. Phonocardiograms were recorded in all patients before mitral valve replacement. We analyzed the presence and the amplitude of opening snap and the amplitude of the first heart sound at the apex. The amplitude of the opening snap was expressed in mm and as a ratio to the maximal vibration of the second sound in the same cycle. The amplitude of the first sound was expressed in mm and as a ratio of the maximal vibration of the first sound to the maximal vibration of the first sound to the maximal vibration of the second sound in the same cycle. All amplitude measurements were made in 10 consecutive cardiac cycles and were then averaged. Then we studied all mitral valves removed in a uniform manner by one surgeon. Excised valves were fixed in 5% solution of formaline. The extent of calcification was determined by radiographs (fig. 1). The mitral valve area and calcification area were estimated by planimetry of radiographs. Then we analyzed the localization of calcification and we calculated the ratio of calcification area to valve area. Valves were divided into three groups according to the degree of the fusion of subvalvular structures ("a funnel") (fig. 2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942751 TI - [HLA histocompatibility antigens in patients with aortic valve defects]. AB - HLA antigens A, B, C were determined in 61 patients with aortic valve disease and in 263 healthy controls. The patients were divided into two subgroups--with rheumatic fever in anamnesis (N = 24) and without (N = 37). In the whole group of patients with aortic valve disease there was a lower frequency of incidence of HLA A3 in comparison to the control group. In the subgroup with rheumatic fever in anamnesis there was a deficit of HLA A3 and a much more frequent incidence of HLA B17, in the subgroup without rheumatic fever a more frequent incidence of HLA A2, A9, A28, B15 was noted in comparison to the control group. This study shows that in 60% of patients with aortic valve disease the etiology is linked not to rheumatic fever but probably to a connective tissue disorder. A deficit of HLA A3 and presence of B17 can be a risk factor for rheumatic fever. PMID- 1942753 TI - [Immunologic processes accompanying heart disease]. PMID- 1942752 TI - [Clinical manifestations of extrinsic and intrinsic sinus node dysfunction (functional and organic factors)]. AB - We analysed the clinical data of 206 patients (pts) with sick sinus syndrome (group S). All the population was divided into two group; pts with normal (104 pts, group S1) and abnormal (102 pts, group S2) "intrinsic" properties of sinus node (SN). Intrinsic properties was defined as normal if intrinsic heart rate was normal and corrected sinus node recovery time after pharmacological heart denervation (propranolol 0.2 mg/kg body weight, atropine 0.04 mg/kg body weight) was no longer than 422 ms. In whole group S, in 131 pts we found organic heart disease (coronary heart disease, n = 102, hypertensive disease, n = 12, mitral valve prolapse, n = 10, history of myocarditis or mild mitral or aortic valve stenosis, n = 7). In groups S1 and S2 coronary heart disease was found in 31 and 71 pts, hypertensive disease in 6 and 6 pts respectively. All the patients with mitral valve prolapse were found in group S1. In 75 pts sinus node disease (SSS) was the only pathological finding, they were divided into group IS1 (n = 51) and IS2 (n = 24) according to the intrinsic properties of the SN. CONCLUSION: 1. In clinical practice sinus node dysfunction seems to be more frequent in men than in women, 2. In the large group of patients with sick sinus syndrome we analysed in this paper in about 36% we did not find any other diseases of the heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942754 TI - [The case of the "runaway pacemaker"]. AB - A case of a runaway pacemaker is described. Malfunctioning pacemaker produced stimuli with changeable amplitude and fast rate. It was a reason of intermittent capture, producing a variable ventricular rate; periods of life-threatening pacemaker-induced ventricular tachycardia or uneffective stimulation with slow ventricular escape rhythm. Although runaway pacemaker is a rare complication in modern pacemakers, but it still exists. It usually occurs as an emergency situation requiring immediate correction. PMID- 1942755 TI - [Management of hyperlipemia. When to administer agents that regulate lipid disorders?]. PMID- 1942756 TI - [Transesophageal echocardiography. Clinical application]. PMID- 1942757 TI - [Views on the treatment of congestive heart failure]. PMID- 1942758 TI - [Cardiology in Poland and in the world]. PMID- 1942759 TI - [Transesophageal and classical echocardiography in myocardial infarction and heart valve disease (comparison study)]. AB - In 85 patients (22 with myocardial infarct and 63 with valvular heart disease) echocardiographical examination simultaneously by classical and transesophageal methods was done. The transesophageal method was better in assessing the aortic valve and similar to the classical method in reference to the mitral valve. Heart contractility assessment was better with the classical method. Transesophageal echocardiography is the method of choice in patients in whom classical echocardiography cannot be done (obesity, emphysema, chest deformation). PMID- 1942760 TI - [Disturbances of myocardial perfusion by exertion scintigraphy in patients with hypertrophic cardiomyopathy and their relationship with sudden death risk factors]. AB - Heart muscle perfusion was studied by exertion scintigraphy Tal-201 in 24 patients, 16M and 8F, aged 16-45 years, means--28 +/- 7.4 years with hypertrophic cardiomyopathy. The relationship between perfusion disturbances and sudden death risk factors occurring in this group of patients was evaluated. Disturbances of heart muscle perfusion were found in 20 pts (83%); 2 pts had permanent perfusion defects, in 18 pts these defects were completely or partially reversible at rest. Only 4 pts (17%) had normal heart muscle perfusion. In patients with perfusion disturbances there was found a significantly more frequent occurrence of the following sudden death risk factors: 1. syncope (p less than .01) 2. ventricular arrhythmia of IV b class according to Lown (p less than .01) 3. advanced hypertrophy of intraventricular septum (p less than .01) 4. sudden death in patients families (p less than .05) The evaluation of the heart muscle perfusion confirmed the occurrence of myocardial ischemia in most of the examined patients. Normal coronaro-angiography in all the patients over 35 years as well as the young age of the other patients exclude atherosclerosis as the cause of myocardiac ischemia in the group under study. This is a confirmation of nonatherosclerotic etiology of myocardiac ischemia in hypertrophic cardiomyopathy patients. The correlation between perfusion disturbances and sudden death risk factors points to the role of ischemia in the natural course of disease and the value of exertion scintigraphy TI-201 in prognosing patients with hypertrophic cardiomyopathy. PMID- 1942762 TI - [Cholesterol and diseases of the cardiovascular system. Skeptical opinions]. PMID- 1942761 TI - [Lovastatin in the treatment of primary hypercholesterolemia]. AB - The results of 12 weeks treatment of primary hyperlipidemias with Lovastatin are presented. This drug belonging to a new generation of hypercholesterolemic drugs inhibits the endogenous synthesis of cholesterol by means of inhibiting the HMG CoA reductase. The sample consisted of 30 men aged 28-68 years: in 17 of them heterozygotic familial hypercholesterolemia (FH) was diagnosed and in 13--primary non familial hypercholesterolemia (NFH). After 12 weeks of treatment in both groups a significant reduction of total serum cholesterol concentration was observed--(-28%) and--(-32%) as well as LDL-cholesterol concentration (in both groups about -37%) and apo B concentration--(-32%) and -34%. Only in one patients with NFH a significant reduction of VLDL-cholesterol (-29%) and or triglycerides (-15%) concentrations was observed. In this group also a 9% increase of HLD cholesterol, mainly HDL-2 concentration, was found. Side effects were observed in 6 patients--in 4 of them a minor increase of ALAT, AsPAT or CPK activities (less than 3 times above norm were observed) without any symptoms and with a spontaneous normalization with no need to stop treatment, and in 2 of them abdominal pains not causing drug treatment cessation. PMID- 1942763 TI - [Metastatic tumor of the right heart successfully removed by surgery]. AB - A case report of a cardiac metastasis from osteosarcoma of the pelvis is presented. The tumor obliterated nearly completely the right atrium and ventricle, inferior vena cava and pulmonary artery. It was successfully treated surgically and during a 9 month follow-up echocardiographical assessment was normal. PMID- 1942764 TI - Proteolytic enzymes as mediators of glomerular injury. PMID- 1942765 TI - Lymphatic removal of dialysate from the peritoneal cavity of anesthetized sheep. AB - Several investigators have suggested that the lymphatic circulation reduces ultrafiltration in continuous ambulatory peritoneal dialysis (CAPD). The purpose of this study was to assess lymphatic drainage of the peritoneal cavity directly in anesthetized sheep under dialysis conditions. Lymph was collected from the caudal mediastinal lymph node and the thoracic duct, both of which are involved in the lymphatic drainage of the ovine peritoneal cavity, and from the prescapular lymph node, which is not involved in peritoneal lymphatic drainage. Fifty ml/kg volumes of a mildly hypertonic dialysis solution (Dianeal 1.5%) containing 25 microCi 125I-human serum albumin were instilled into the peritoneal cavity, and lymph flows and the appearance of labeled protein in the lymphatic and vascular compartments were monitored for six hours. Following the instillation of dialysis fluid there was a tendency for lymph flow rates from the thoracic duct to increase but these changes were not significant. However, flow rates from the caudal lymphatic demonstrated significant increases, especially in the final three hours of the monitoring period. Only about 8% of the radiolabeled albumin was removed from the peritoneal cavity over six hours (that is, 92% was left in the peritoneal space). Of the albumin removed, approximately 17% of this was drained by abdominal visceral lymphatics into the thoracic duct. About 25% passed through the diaphragm into the caudal mediastinal lymph node and into efferent lymph. Since the efferent lymphatic duct of the caudal mediastinal node empties directly into the thoracic duct, about 42% of all protein removed from the peritoneal cavity of the sheep was ultimately transported to the thoracic duct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942766 TI - Doses of endothelin have natriuretic effects in conscious rats with cirrhosis and ascites. AB - MAP, RPF, GFR, V and UNaV were measured in nine conscious control and in 11 conscious cirrhotic rats with ascites before and following two bolus injections (100 and 600 pmol/kg body wt) of endothelin (ET). PRA and plasma concentration of aldosterone and ANP were measured in basal conditions and following the high dose ET. ET induced similar increase in MAP and decrease in RPF and GFR in control and cirrhotic rats. High-dose ET produced a significant reduction in UNaV in control rats (from 2.22 +/- 0.46 to 1.14 +/- 0.28 microEq/min, P less than 0.01). By contrast, it induced marked natriuresis in cirrhotic rats (from 0.76 +/- 0.18 to 2.31 +/- 0.70 microEq/min, P less than 0.05). ET significantly increased aldosterone (control rats: 59.3 +/- 2.2 vs. 85.4 +/- 7.4 ng/dl, P less than 0.025; cirrhotic rats: 115.0 +/- 15.8 vs. 163.9 +/- 30.8, ng/dl, P less than 0.05) and ANP (control rats: 20.1 +/- 3.4 vs. 42.7 +/- 7.7, fmol/ml, P less than 0.025; cirrhotic rats: 107.5 +/- 17.3 vs. 214.2 +/- 41.1, fmol/ml, P less than 0.025) and significantly suppressed PRA (control rats: 2.5 +/- 0.5 vs. 0.2 +/- 0.04, ng/ml.hr, P less than 0.025; cirrhotic rats: 16.6 +/- 2.9 vs. 5.0 +/- 1.1, ng/ml.hr, P less than 0.01) in both groups of animals. These results indicate that ET has marked natriuretic properties in cirrhosis with ascites due to inhibition of tubular sodium reabsorption. PMID- 1942767 TI - Cause of variable therapeutic efficiency of angiotensin converting enzyme inhibitor on glomerular lesions. AB - We tested the effect of angiotensin I converting enzyme inhibitor (ACEI) on established glomerular sclerosis. Starting eight weeks after subtotal nephrectomy (sNPX), rats were given enalapril for four weeks in a dose of 50 (Group II, N = 5) or 200 mg/liter drinking water (Group III, N = 5). A third group of sNPX rats not given ACEI served as control (Group I, N = 10). Glomerular sclerosis index (S1, 0 to 4 scale) was assessed three-dimensionally on serial thin sections for individual glomeruli at biopsy (Bx, 8 weeks), and divided into four different ranks of severity and compared to autopsy (Ax, 12 weeks). In Group I control rats, 48% of the glomeruli at Bx had SI between 0 and 1 (rank 1, average: 0.49 +/ 0.06), 36% between 1 and 2 (rank 2, average: 1.53 +/- 0.06), 9% between 2 and 3 (rank 3, average: 2.45 +/- 0.12) and 7% between 3 and 4 (rank 4, average: 3.54 +/ 0.10). Glomeruli of the same rats at Ax were ranked according to severity of sclerosis, and then divided into percentile groups, corresponding to the percent of distribution at Bx. The 48% least sclerotic glomeruli at Ax had average SI of 0.69 +/- 0.08, the next 36% 2.58 +/- 0.11, and next 9% 3.97 +/- 0.02 and the most sclerotic 7% 4.00 +/- 0.00. Thus, sclerosis advanced during the last four weeks after biopsy in all glomeruli, with more accelerated progression occurring toward later stages of sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942768 TI - Stimulated kidney tubular epithelial cells express membrane associated and secreted TNF alpha. AB - Tumor necrosis factor-alpha (TNF alpha) is a pleiotropic, pro-inflammatory peptide cytokine which promotes immune renal injury, and participates in T cell activation. It is produced by macrophages, T cells, and some non-hematopoietic cells, and is cytotoxic in picogram quantities. As renal tubular epithelial cells (TEC) bearing MHC class II (Ia) antigens and adhesion molecules (ICAM-1) can act as immune accessory cells, the ability of TEC to produce costimulatory cytokines could augment TEC accessory capacity in vivo. We report that transformed TEC express low levels of TNF alpha in response to LPS or IL-1 alpha as a secreted product and as a cytotoxic membrane associated molecule displayed on the cell surface. Surface labelling and immunoprecipitation studies of TEC detect a number of bands including a prominent 26 kD protein, which is the predicted size of TNF alpha precursor. TNF alpha mRNA transcripts were also detected by in situ hybridization in cortical tubules of C3H/FeJ mice injected with LPS, demonstrating the capacity of normal tubular epithelial cells to express TNF alpha in vivo. This report demonstrates for the first time the ability of kidney tubular cells to express TNF alpha protein and that membrane associated TNF alpha is not limited to hematopoietic cells. The function of small amounts of TNF displayed on the surface of tubular cells may be amplified by the abundance of these cells within the renal cortex, and may allow TEC to modulate immune responses within the kidney during inflammation. PMID- 1942769 TI - Effects of 1,25(OH)2D3 on compensatory renal growth in the growing rat. AB - Renal compensatory growth after uninephrectomy (UNX) was examined in vitamin D replete male 100 g Sprague-Dawley rats. Five days after UNX, the contralateral kidney wet weight increased by 25% with the kidney weight/body weight ratio reaching a plateau by day 7 after UNX. The early weight increase was primarily due to an increased cell number, as evaluated by a stereological technique in perfusion-fixed kidneys. Twenty pmol 1,25(OH)2D3 by daily s.c. injection increased time-averaged 1,25(OH)2D3 concentrations 3.3-fold and reduced the increment in the kidney weight of UNX pairfed rats compared to solvent UNX controls. The number of mitoses (whole kidney and different nephron segments) were significantly reduced by giving 1,25(OH)2D3 to UNX animals at different levels of food intake. The effect was also demonstrable in PTX animals on a constant infusion of exogenous PTH (100 ng/kg/hr 1,34 bPTH by osmotic minipump). The data suggest that changes of 1,25(OH)2D3 concentration within a physiologically relevant range modulate compensatory (and possibly basal) growth of the kidney. PMID- 1942770 TI - Calcitonin, an important factor in the calcemic response to parathyroid hormone in the rat. AB - The role of calcitonin on the calcemic response to parathyroid hormone (PTH) in renal failure has not been evaluated previously. Often animal studies evaluating the calcemic response to PTH in renal failure are performed in thyroparathyroidectomized (TPTX) animals, and thus eliminate any potential physiologic effect of calcitonin. In addition, parathyroidectomy (PTX), presumably by reduction of high PTH levels, has corrected the calcemic response to PTH in animals with renal failure. The present study was designed to evaluate the effect of endogenous calcitonin production on the calcemic response to PTH in rats with renal failure and secondary hyperparathyroidism, and in rats with normal renal function with diet induced hyperparathyroidism. Four groups of rats were evaluated: 1) chronic renal failure plus TPTX with autotransplant of the parathyroid gland, (CT-) CRF; 2) chronic renal failure plus selective PTX with autotransplant of the parathyroid gland, (CT+) CRF; 3) normal renal function plus TPTX with autotransplant of the parathyroid gland, (CT-) NRF; and 4) normal renal function plus selective PTX with autotransplant of the parathyroid gland, (CT+) NRF. Renal failure was surgically induced by a two-stage 5/6 nephrectomy, and exogenous thyroxine was administered to the two thyroidectomized (CT-) groups. Hyperparathyroidism was induced with a high phosphate diet (1.2%), and thus at the time of PTH infusion, PTH levels were (CT-) CRF 84 +/- 16, (CT+) CRF 89 +/- 21, (CT-) NRF 37 +/- 7, and (CT+) NRF 31 +/- 4 pg/ml, respectively (normal 21 +/- 3 pg/ml). Rat 1-34 PTH (2.6 U/hr) was infused for 48 hours via a subcutaneously implanted Alzet pump.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942771 TI - Mesangial structure and function in the remnant kidney. AB - The pathogenetic significance of changes in mesangial structure and function were studied in hypertensive (HT) (BP +/- SD = 173 +/- 23 mm Hg, N = 13) and normotensive (NT) (130 +/- 17 mm Hg, N = 12) WKY rats with 5/6 nephrectomy and compared to sham-operated controls (SHAM) (121 +/- 11 mm Hg, N = 12). Rats were fed a 24% protein diet and studied six to eight week after surgery. Acute glomerular necrosis was present in 6/13 HT, 1/12 NT, and 0/12 SHAM, and glomerular sclerosis was seen in 7/13 HT, 4/12 NT, and 0/12 SHAM. HT and NT had glomerular and tubular hypertrophy compared to SHAM (mean glomerular diameter +/- SD. HT = 174 +/- 17 mu and NT = 171 +/- 12 cf. SHAM = 142 +/- 11, P = 0.0012, ANOVA). The fractional mesangial volumes, determined by ultrastructural morphometry, were similar in all groups, but the absolute volumes were increased in the HT and NT (HT = 323 +/- 103 mu3 x 10(-3) and NT = 335 +/- 75 cf. SHAM = 164 +/- 20, P = 0.01, ANOVA). Mesangial clearance of aggregated rat IgG (AgRalgG) was studied in serial biopsies by immunofluorescence microscopy. Following i.v. injection, mesangial AgRalgG appeared increased in HT and NT over SHAM for four hours, but after 24 hours, the label had disappeared from the mesangium in all groups. We conclude that neither increased mesangial volume nor abnormalities of mesangial clearance of macromolecules plays a role in the pathogenesis of the acute, necrotizing glomerular lesion which was mainly seen in HT rats. On the other hand glomerular sclerosis, seen in both NT and HT rats but not sham controls, may result from more than one mechanism. In the HT rats scarring may result from healing of the acute glomerular lesions. Although we have excluded the mesangial clearance function as a factor in the pathogenesis of glomerular sclerosis, the presence of glomerular scarring in NT rats suggests that the lesions may result from dysfunction of other glomerular cells or unmeasured mesangial cell functions. PMID- 1942772 TI - Nature and extent of glomerular injury induced by cyclosporine in heart transplant patients. AB - We sought to clarify whether low-dose cyclosporine (5.0 +/- 2.2 mg/kg/day) given for more than two years to prevent cardiac graft rejection induced glomerular injury and to quantify the extent of the lesions. After renal hemodynamic studies, renal biopsy specimens were obtained from 10 patients on cyclosporine and analyzed by a novel morphometric technique consisting of a tridimensional reconstruction of the glomerular tuft. Autopsy kidney specimens from three patients with no clinical history of renal disease, and from four patients who died with dilatative cardiomyopathy served as controls. The glomerular filtration rate and renal plasma flow were significantly depressed below normal values in transplant recipients given cyclosporine, averaging 35 +/- 8 and 325 +/- 94 ml/min/1.73 m2, respectively. Conventional light microscopy of specimens from controls and from patients who died with dilatative cardiomyopathy did not reveal renal structural abnormalities. By contrast kidney specimens from cyclosporine treated patients had obliterative arteriolopathy and ischemic-type changes, with thickening and wrinkling of glomerular capillary wall. Morphometrical analysis of 28 control glomeruli and 40 glomeruli from patients with dilatative cardiomyopathy showed glomerular capillary tuft volumes (VCT) ranging between 1.2 and 2.3 microns 3 x 10(-6), whereas of 102 glomeruli from cyclosporine-treated patients 42.1% had VCT lower than 1.2 microns 3 x 10(-6) and 24.4% VCT higher than 2.3 microns 3 x 10(-6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942773 TI - Insulin increases sodium reabsorption in diluting segment in humans: evidence for indirect mediation through hypokalemia. AB - To examine the mechanism of renal sodium (Na) and potassium (K) retention during insulin infusion, seven healthy volunteers underwent clearance studies without (time control) and with insulin infusion (40 mU bolus, followed by 1 mU/kg/min for 150 min). Maximal free water clearance and fractional lithium clearance (FELi) were used to analyze renal sodium handling. Insulin decreased Na excretion (from 189 +/- 25 to 121 +/- 19 mumol/min, P less than 0.01) and K excretion (from 64 +/- 8 to 19 +/- 1 mumol/min, P less than 0.01), but did not change in glomerular filtration rate. FELi increased from 29.8 +/- 1.9 to 32.3 +/- 1.9% (P less than 0.05), minimal urine osmolality decreased from 59 +/- 3 to 46 +/- 3 mOsm/kg (P less than 0.01), and the diluting segment reabsorption index increased from 88.0 +/- 0.9 to 93.7 +/- 0.9%, P less than 0.01). Insulin also decreased plasma K, from 3.91 +/- 0.08 to 3.28 +/- 0.08 mmol/liter, P less than 0.01. In a third clearance study KCl was infused simultaneously (3.75 mumol/kg/min) to prevent this fall in plasma K. In this study insulin had no effect on Na and K excretion and diluting segment reabsorption, but the rise in FELi remained. In a fourth clearance study NaCl (3.75 mumol/kg/min) instead of KCl was infused together with insulin. This maneuver did not prevent the Na and K retaining effect of insulin, nor any of its effects on renal sodium handling parameters. These data suggest that Na and K retention during insulin infusion are largely secondary to hypokalemia, which causes increased reabsorption in the diluting segment. PMID- 1942774 TI - Regulation of interleukin-2 and interferon-gamma gene expression in renal failure. AB - Regulated expression of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) genes, induced in cultured peripheral blood mononuclear cells from patients with end-stage renal disease on hemodialysis (HD; N = 13) or peritoneal dialysis (PD; N = 13), was compared to that of 32 normal donors. Culture conditions were chosen that measure the transient, phytohemagglutinin-induced expression of IL-2 and IFN gamma messenger RNA (mRNA), as well the intactness of post-transcriptional and suppressor T cell-dependent mechanisms that control this expression. The latter was achieved by analyzing the superinduction of IL-2 and IFN-gamma mRNA occurring upon culture with cycloheximide or after low-dose gamma-irradiation, respectively. HD subjects showed a complete loss of inducibility of the IL-2 gene, concomitant with decreased inducibility of IFN-gamma mRNA. In PD subjects, by contrast, expression of IL-2 mRNA was as vigorous as in normal donors, while IFN-gamma mRNA was even more strongly inducible. This difference in gene inducibility is caused by a lack of T cell function in HD subjects. The defect in IL-2 gene expression in HD subjects, occurring most likely at transcription, may underly their impaired immune function. PMID- 1942775 TI - Protective action of glycine in cisplatin nephrotoxicity. AB - Because glycine is cytoprotective for kidney cells in vitro, we investigated its possible action in vivo to protect rats against cisplatin nephrotoxicity, a well established experimental model of renal tubular injury. Glycine was infused at a dose of 1 mmol per 100 g body weight per hour for 75 minutes, starting 15 minutes before cisplatin, 5 mg per kg, was injected intravenously. Plasma concentration of glycine rose to 3.5 mmol per liter at the time cisplatin was injected. These rats were compared with cisplatin-treated animals treated with L-alanine or with isotonic saline. After five days plasma creatinine of saline-treated rats given cisplatin had risen threefold to 2.6 +/- 1.5 mg per 100 ml (mean +/- SD), as creatinine clearance fell to 25% of baseline (0.14 +/- 0.05 ml/min/100 g). Morphological evaluation disclosed extensive damage involving all S3 segments in the outer medulla as well as the medullary rays of the cortex. In contrast, in rats treated with glycine, plasma creatinine rose only to 1.2 +/- 0.2 mg/100 ml and creatinine clearance was maintained at 75% of baseline (0.35 +/- 0.05 ml/min/100 g). Glycine also attenuated the weight loss, polyuria, increased fractional excretion of sodium and potassium, decreased urinary osmolality, and renal glycosuria observed in control, saline-treated rats after cisplatin, while substantially decreasing the percentage of S3 tubules with evident morphological injury. Renal platinum content was unaffected by glycine. The administration of L alanine or the delayed infusion of glycine, starting one hour after cisplatin was given, did not prevent cisplatin toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942776 TI - Urine glycosaminoglycans in congenital and acquired nephrotic syndrome. AB - To evaluate the specificity of a raised heparan sulphate (HS) excretion previously reported in four children with congenital nephrotic syndrome (CNS), we measured the urinary excretion of HS and chondroitin sulphate (CS) in seven children with Finnish-type congenital nephrotic syndrome (CNSF), seven with diffuse mesangial sclerosis (DMS), nine with focal segmental glomerulosclerosis (FSGS), 14 with steroid-sensitive nephrotic syndrome of whom eight had a biopsy confirming minimal change histology (SSNS), and 17 controls. The urine HS/CS ratio in normal children had a median of 0.36 (observed range 0.21 to 0.68) and was independent of age. HS/CS ratio was significantly greater than controls in CNSF (median 0.80, range 0.43 to 1.28), DMS (median 0.81, range 0.49 to 1.13) and FSGS children (median 0.66, range 0.38 to 1.6), but was not in SSNS (median 0.44, range 0.28 to 0.70). There was a positive correlation between the HS/CS ratio and urine albumin excretion. High HS/CS ratios are not diagnostic of a particular histological variety of CNS. PMID- 1942777 TI - Stimulation of beta 2-microglobulin synthesis in lymphocytes after exposure to Cuprophan dialyzer membranes. AB - We tested beta 2-microglobulin (beta 2m) synthesis by peripheral blood lymphocytes of non-uremic donors after contact with dialyzer membranes. Under serum-free conditions, lymphocytes were incubated with different dialyzer membranes for four hours. After subsequent culture in the absence of membranes to yield an overall culture time of 24 hours, RNA was extracted. Messenger RNA for beta 2m was quantitated by Northern blotting with specific probes. Increased beta 2m mRNA was seen after a minimum of one hour contact time with Cuprophan both in the presence and absence of cycloheximide. While no consistent stimulation was seen with polyacrylonitrile or polycarbonate-polyether membranes, respectively, the stimulation of beta 2m mRNA with Cuprophan was of the same order of magnitude as that obtained with interferon gamma. Stimulation of beta 2m mRNA by Cuprophan was stereospecifically diminished by 5 mM L-fucose. Apart from stimulated transcription of beta 2m we could also show increased surface expression of MHC class I molecules, using FACS technique. The results further prove complement independent blood cell activation by Cuprophan membranes. It is uncertain whether the results are relevant for beta 2m amyloidosis. PMID- 1942778 TI - Glucocorticoid activates glomerular antioxidant enzymes and protects glomeruli from oxidant injuries. AB - We examined the effect of glucocorticoid on intrinsic glomerular antioxidant enzyme (AOE) activities. Munich-Wistar rats were treated with daily i.p. injection of vehicle or methylprednisolone [MP, 15 mg/kg body wt, (MP15)] either for three days or nine days. Glomeruli isolated from rats given MP15 had significantly higher activities of total (T-) and manganese (Mn-) superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase than vehicle treated rats (P less than 0.05). MP15-treated rats were subjected to intrarenal arterial infusion of hydrogen peroxide (35 mumol over 1 hr). Values for urinary protein excretion rate (UprV) after hydrogen peroxide infusion were markedly lower in rats pretreated with MP15 for both three days and nine days than in untreated rats (109 +/- 18 and 55 +/- 24 vs. 416 +/- 73 micrograms/min, respectively, both P less than 0.005). To test whether the same therapeutic intervention attenuates reactive oxygen species (ROS)-mediated glomerular injury in another model, rats given a single i.v. dose of puromycin aminonucleoside (PAN) (50 mg/kg body wt) were treated with daily i.p. injection of vehicle or MP15. Two days after PAN administration, when compared to vehicle-treated controls, PAN rats given MP15 had significantly higher activities of Mn-SOD, GSH Px and catalase. After eight days of PAN injection, T- and Mn-SOD activities were, likewise, significantly higher in MP15- than vehicle-treated PAN rats. PAN rats given MP15 also had substantially less proteinuria, compared to PAN rats given vehicle alone, UprV averaging 32.3 +/- 9.4 versus 159.0 +/- 13.8 mg/24 hr (P less than 0.05). Elevated glomerular malondialdehyde (MDA) level characteristic of PAN rats was absent in rats treated with MP15. Moreover, epithelial foot process fusion and cell vacuolization seen in vehicle-treated PAN rats were markedly attenuated in MP15-treated PAN rats. These data indicate that the mechanism for therapeutic effect of glucocorticoids on ROS-mediated renal injuries includes an enhancement of endogenous glomerular AOE activities, which attenuates lipid peroxidation of glomerular tissue. PMID- 1942779 TI - Effect of salt supplementation on amphotericin B nephrotoxicity. AB - It has been suggested that salt loading protects against amphotericin B-induced nephrotoxicity. The influence of saline loading on the nephrotoxic response to amphotericin B (50 mg/dose given i.v. over 4 hr 3 X/week for 10 weeks) was assessed in two groups of ten patients each who were diagnosed with mucocutaneous leishmaniasis. Patients were randomized to receive either 1 liter of 0.9% saline or 1 liter of 5% dextrose in water, administered i.v. over one hour in a double blinded manner, directly prior to amphotericin B administration. Renal function was monitored on a weekly basis two days after the last dose of amphotericin B. Baseline characteristics were similar in both groups except for a slightly higher serum creatinine concentration (Cr) in the saline group (0.8 +/- 0.05 vs. 0.6 +/- 0.04 mg/dl). Baseline sodium (Na) excretion was relatively high (262 +/- 23 mmol/day in the dextrose group and 224 +/- 17 mmol/day in the saline group). None of the patients sustained an increase in Cr to values greater than 1.7 mg/dl. Although mean Cr remained within normal, there was a significant difference between the two groups over the ten week period, with the dextrose group sustaining a significant increase in Cr and the saline group remaining unchanged. Serum potassium (K) levels fell in both groups necessitating oral K supplementation. The saline group required significantly greater amounts of K supplementation to maintain a normal serum K. Amphotericin B caused a rapid reduction in the acidification ability of the kidney in response to an ammonium chloride load. Under these conditions, the saline group had a poorer ability to acidify the urine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942781 TI - Computer simulations of peritoneal fluid transport in CAPD. AB - To model the changes in intraperitoneal dialysate volume (IPV) occurring over dwell time under various conditions in continuous ambulatory peritoneal dialysis (CAPD), we have, using a personal computer (PC), numerically integrated the phenomenological equations that describe the net ultrafiltration (UF) flow existing across the peritoneal membrane in every moment of a dwell. Computer modelling was performed according to a three-pore model of membrane selectivity as based on current concepts in capillary physiology. This model comprises small "paracellular" pores (radius approximately 47 A) and "large" pores (radius approximately 250 A), together accounting for approximately 98% of the total UF coefficient (LpS), and also "transcellular" pores (pore radius approximately 4 to 5 A) accounting for 1.5% of LpS. Simulated curves made a good fit to IPV versus time data obtained experimentally in adult patients, using either 1.36 or 3.86% glucose dialysis solutions, under control conditions; when the peritoneal UF coefficient was set to 0.082 ml/min/mm Hg, the glucose reflection coefficient was 0.043 and the peritoneal lymph flow was set to 0.3 ml/min. Also, theoretical predictions regarding the IPV versus time curves agreed well with the computer simulated results for perturbed values of effective peritoneal surface area, LpS, glucose permeability-surface area product (PS or "MTAC"), intraperitoneal dialysate volume and dialysate glucose concentration. Thus, increasing the peritoneal surface area caused the IPV versus time curves to peak earlier than during control, while the maximal volume ultrafiltered was not markedly affected. However, increasing the glucose PS caused both a reduction in the IPV versus time curve "peak time" and in the "peak height" of the curves. The latter pattern was also seen when the dialysate volume was reduced. It is suggested that computer modelling based on a three-pore model of membrane selectivity may be a useful tool for describing the IPV versus time relationships under various conditions in CAPD. PMID- 1942780 TI - Acute renal failure with preserved renal plasma flow induced by cancer immunotherapy. AB - Adoptive immunotherapy in patients with advanced cancer produces significant regression of metastatic disease in selected patients, but it is complicated by severe side effects. Prevention of these complications is still limited because their precise mechanisms remain unknown. For this reason we have investigated renal function and hemodynamic parameters in 16 patients with renal cell carcinoma before and during treatment with a combination of high doses of both recombinant interleukin-2 (rIL2) and recombinant alpha-interferon. After patients had received three injections of combined immunotherapy, there was a decrease in mean blood pressure (-20%), glomerular filtration rate (-25%), urine output ( 50%), and fractional sodium excretion (-0.8%). This was associated with an increase in heart rate (+30%), plasma creatinine level (+30%), fractional potassium excretion (+14%) and microalbuminuria (+130%). However, renal plasma flow remained constant. The increment in microalbuminuria may reflect an alteration of glomerular capillary permeability. The reduction in GFR may be accounted either for a decrease in efferent to afferent arteriolar resistance ratio, leading to a decrease in glomerular capillary pressure, or for a decrease in ultrafiltration coefficient, or both. Nonsteroidal antiinflammatory drugs, such as ketoprofen, used to minimize side effects, could considerably worsen renal function and should be avoided in patients treated by rIL2. Our results bring new insights into the pathogenesis of functional acute renal failure and provide a rational basis for the use of vasopressors in the treatment of cytokine induced acute renal failure. PMID- 1942782 TI - Dietary protein restriction in patients with chronic renal failure. PMID- 1942783 TI - [Significance of electroencephalography in the physical examination of children with encopresis]. AB - At an one time transversal examination 28 of 36 children with encopresis exhibited abnormal findings, increased incidence of sharp waves, a back ground that was too slow for their age and subcortical dysfunctions was striking. The abnormalities are approached as constitutional risks and maturational retardation with increased environmental propensity. Increased frequency of enuresis and encopresis in premature craniosynostosis was found. Electroencephalography should be used in paediatric and child psychiatric examination as a not burdening screening method for clarifying the aetiologic conditions of encopresis and getting hints of brain maturation, constitutional disorders and may be signs of brain damage. PMID- 1942784 TI - [Psychomotor development of children at risk with special reference to prenatal, intrapartum and postnatal hypoxia]. AB - In a prospective study the psychomotor development of an unselected collective of high risk newborn infants up to the end of the second year of life was examined. The proof of hypoxia was performed with the erythrocytic density test (EDT). The value of EDT showed a decline with the age of life, and it was independent of gestational age or of birthweight only at the first point of determination (cord blood, first or second day of life). Significant connections between the level of light red blood cells and the children's development could not be demonstrated, although the probability to develop psychomotor disabilities increased in the newborn with a positive value of EDT. The diagnostic value of EDT showed the best results for intrapartum and postnatal hypoxia. The highest specificity was calculated with 38.0%, if the sensitivity is 80.0%. In conclusion of these results it's not to be recommended to use the EDT alone for the prediction of individual prognosis of children. PMID- 1942785 TI - [Comparative studies of the activity of disaccharidases in the mucosa of the small intestines in dystrophic, formerly hypotrophic-born young children and of patients with flat mucosa of various etiology]. AB - The disaccharidase activities of the mucous membrane of the small intestine were determined in formerly hypotrophic children who showing a dystrophy with a morphological normal mucosa (n = 36), patients with a flat mucosa caused by enteral protein intolerances of different genesis (n = 27), patients with a morphologically and functionally normal mucosa (n = 51). In about half of the former small-for-date children were shown activities lower than the simple standard deviation of the normal value, for lactase n = 17, for sucrase n = 14, for maltase n = 12. Some children showed pathologically reduced activities even below the double standard deviation for the normal value: lactase n = 8, sucrase n = 5, maltase n = 3. PMID- 1942786 TI - [Crouzon syndrome (Mc K 12350)]. PMID- 1942787 TI - [Loschge type of cloverleaf-skull syndrome (Mc K 14880)]. PMID- 1942788 TI - [70th anniversary of the journal "Clinical Surgery"]. PMID- 1942789 TI - [Study of the anal sphincter in children]. AB - In dynamic study of the distal colon in children, the functional and electrophysiological methods of diagnosis developed and introduced by the authors: determination of anal reflex, electrosensitivity of the anal canal, musculocutaneous electrosensitivity, state of the genital nerve and its branches were used. The new methods of investigation permit to determine by the objective indices of the strength of the current and changes in pressure in the anal canal a state of the "sacral reflex arch" and neuromuscular apparatus of the external anal sphincter. In patients with constipation, a decrease in electrosensitivity and attenuation of reflex interconnection between the rectum and anal canal were noted. PMID- 1942790 TI - [Clinico-morphologic basis for choosing the surgical method in the treatment of exstrophy of the bladder]. AB - A method for creation of an artificial bladder from the rectum, which was used in 22 children with exstrophy of the bladder with good anatomic and functional results is suggested. In clinical and histologic studies, the inferiority of the exstrophied bladder tissues and unexpediency of their use for plasty have been proved. A long-term result of treatment in 31 of the 35 patients operated on with the use of different methods was studied by the data of complex evaluation of the functions of an artificial bladder, upper urinary tracts and rectal sphincter apparatus. PMID- 1942791 TI - [Latissimus dorsi muscle flap for autologous myoplasty in children with sequelae to obstetric paralysis of the Duchenne-Erb type]. AB - Within 1987-1989, surgical correction of sequelae to obstetrical paralysis of an upper extremity of the Duchenne-Erb type was accomplished in 26 children. In 11 cases, the operations of transposition and lengthening of the adductor brachial muscles were supplemented with a non-free transfer of a thoracico-dorsal flap on a neurovascular bundle to the position of a musculus deltoideus. With the aim of active functional influencing on a myotransplant at the early postoperative period, the neural stimulation and adaptive bioregulation with the outer feedback were used. For control, the continuous electroneuromyography was used. A good functional result was obtained. PMID- 1942792 TI - [Correction of postoperative complications of water-electrolyte balance in children with acute pathology of the abdominal organs]. AB - In children with acute surgical pathology of the abdominal organs in intraintestinal administration of saline solutions, the normalization of the indices of homeostasis and restoration of motor activity of the intestine after the operation were more rapid than in use of parenteral treatment. PMID- 1942793 TI - [Anesthesiologic and postoperative complications in children with isolated forms of funnel chest]. AB - In thoracoplasty for isolated funnel-shaped deformity of the chest in children, the main anesthesiologic complications which develop are the following: delayed restoration of muscular tonicity and adequate respiration and disorders in cardiac rhythm. At the postoperative period, the complications, are mainly caused by injury to parietal pleura at intervention. The pulmonary, cardiac, gastroenterologic and hemorrhagic complications were observed less often. PMID- 1942794 TI - [Enteral detoxication using polymethylsiloxane in the comprehensive treatment of septic forms of acute hematogenous osteomyelitis in newborn babies]. AB - With regard for the role of bacterial and viral toxins and proteases in the pathogenesis of septic forms of acute hematogenous osteomyelitis, the use of enteral detoxication in the pediatric practice has been substantiated. The authors within 1988-1989, in 35 newborns with septic forms of acute hematogenous osteomyelitis used for detoxication the "Enterosgel" preparation. Control of the state of patients was accomplished by means of bacteriologic, biochemical and immunologic methods. A high detoxicative and antiinflammatory activity of the preparation and its harmlessness for the newborns have been proved. PMID- 1942795 TI - [Early commissural ileus after appendectomy in children]. AB - The results of treatment of early commissural ileus (ECI) after appendectomy in children for the period of from 1971 to 1988 are presented. Before 1980, the active tactics of treatment was predominantly used. Of the 4412 patients who underwent appendectomy, ECI developed in 28 (0.68%), 18 were operated on, including the 7--repeatedly. Since 1980, the complex of conservative measures permitting to avoid the operative intervention more than in 60% of the patients has been introduced. Of the 4281 patient operated on for acute appendicitis, ECI developed in 12 (0.28%). The conservative measures has proved to be effective in 2/3 patients. Recurrency of commissural ileus was noted in 1 patient. There were no lethal outcomes. PMID- 1942796 TI - [Acute appendicitis in infants]. AB - The analysis of the effectiveness of treatment of 12 infants with acute appendicitis was carried out. The authors distinguished three forms of the course of acute appendicitis. PMID- 1942797 TI - [Acute appendicitis in children with atypical location of the vermiform process]. AB - The analysis of case records of 19,966 children operated on for acute appendicitis at the Belorussian centre of pediatric surgery for 15 years (from 1970 till 1984) is presented. In 2796 (14%) children, the atypical location of the vermiform process was diagnosed at operation. In atypical location of the vermiform process, the clinical manifestations of acute appendicitis differ from those in its common location: abdominal pain is most frequently (47.8% of cases) localized outside the inguinal region, less often, tensity of the anterior abdominal wall muscles, symptoms of peritoneal irritation are noted. Children with acute appendicitis in atypical location of the vermiform process twice later (when compared with patients with its typical location) are admitted to the hospital, and as well twice longer are observed before the operation. The incidence of complications after the operation is more than two-fold greater. PMID- 1942798 TI - [Tactics in the surgical treatment of children with strangulated inguinal hernia]. AB - The authors have developed a technique for conservative taxis of the incarcerated inguinal hernia in boys, which they used in 164 of the 195 children. In ineffectiveness of the conservative taxis, incarceration of hernia in girls, admission to the hospital later than 12 h from the moment of incarceration, 36 patients were operated on. There were no lethal outcomes. Introduction into practice of the technique suggested by the authors will permit to decrease considerably the lethality in incarcerated inguinal hernia in children. PMID- 1942799 TI - [Intestinal invagination in children older than one year]. AB - The results of treatment of 51 children at the age over 1 year with intestinal invagination were analysed. Intestinal invagination in them is caused by the organic factors, the course is atypical, clinical signs--as in other acute abdominal diseases. For timely diagnosis of intestinal invagination, it is necessary to use the roentgenological, endoscopic methods of investigation and laparoscopy. Rational tactics permitted the authors to achieve the positive results of treatment in all the patients. PMID- 1942800 TI - [Modern aspects of reduction of mortality in acute appendicitis in children under three years of age]. AB - The experience with treatment of 216 young children with acute appendicitis is summarized. All the patients were operated on after the complex preoperative preparation. Median laparotomy was performed in 17 patients, 199 were operated on with local approach. Sanation of the abdominal cavity, intestinal decompression were performed. At the postoperative period, the correction of metabolic disorders, hemosorption, lymphosorption, endolymphatic antibiotic therapy, intravascular laser and ultra-violet irradiation of the blood were performed. One patient, who was admitted 10 days after the onset of the disease died. There are the following reserves for reduction of lethality: timely taking medical advice, early diagnosis of the disease, effective preoperative preparation, adequate operative intervention and postoperative management of a patient, timely detection and elimination of complications. PMID- 1942801 TI - [Failure of intestinal anastomosis in newborns]. AB - The analysis of clinical course of the immediate postoperative period in 295 newborns who had the intestinal anastomosis placed was carried out. In 31 (10.5%) child, a failure of the anastomotic sutures was revealed. A dependence of the clinical course of this complication on manifestations of peritonitis, concomitant diseases and degree of an organism maturity was determined. A difficulty to diagnose the anastomotic suture leakage is shown. The indications for operative and conservative treatment were established. Causes of the complication development were revealed. PMID- 1942802 TI - [Effect of hyperbaric oxygenation on normalization of intestinal function after surgical treatment of Hirschsprung disease and anorectal developmental defects in children]. AB - Performed were 264 procedures of hyperbaric oxygenation (HBO) in 93 children operated on for Hirschsprung's disease and anorectal developmental defects. The positive effect of HBO on the main links of pathogenesis of many postoperative complications caused by general and local hypoxia was noted. HBO contributes to improvement in viability of the intestinal wall, stabilizes intestinal peristalsis, decreases retention of liquid in the stomach and likelihood of the anaerobic infection development. Performance of hyperbaric oxygenation in combination with the conventional principles of postoperative therapy permits to shorten the duration of the use of parenteral nutrition, decrease a frequency of purulent-septic complications. PMID- 1942803 TI - [Hyperbaric oxygenation in the comprehensive treatment of children who had operations on the abdominal organs]. AB - After the operation on the abdominal organs in 98 children ranging in age from 2.5 mos to 13 yrs, hyperbaric oxygenation (HBO) was included into the complex of therapeutic measures. Regime of HBO and number of seanses were chosen depending on a type of operative intervention and severity of the course of the main disease. The authors consider expedient the early (2-4 h after the operation) use of HBO, including the patients who had the intestinal anastomosis placed. The tactics of treatment with the use of HBO of postoperative functional ileus is presented. PMID- 1942804 TI - [Correction of postoperative fecal incontinence in children]. AB - The results of surgical treatment of II-III degree incontinence of feces in 6 patients previously operated on for anorectal anomaly are presented. Clinico functional examination permitted topical verification of damage to rectal sphincter apparatus. Sphincterolevatoroplasty with the use of a posterior sagittal approach was performed. The given approach permitted maximum use of the preserved muscular elements of the obturator apparatus. In a number of cases sphincterolevatoroplasty was combined with smooth muscle plasty of the internal anal sphincter from the distal colon. The functional results followed in 5 patients were considered as good and satisfactory ones. PMID- 1942805 TI - [A cyst of the urinary duct]. PMID- 1942806 TI - [Surgery of pathologic fractures of the metacarpal bones in children]. AB - The experience with the use of a method of bone plasty developed by the authors in the treatment of 13 children with a pathologic fracture of metacarpal bones is summarized. In follow up of from 1 to 6 years, the complete reconstruction of a transplant with replacing the defects by bone tissue which do not differ in structure from the own one was noted. A hand function restored to the full volume. No impairment in growth was noted. PMID- 1942807 TI - [Surgical treatment of supraventricular tachycardia]. AB - Surgical treatment of supraventricular tachycardia was performed in 61 patient, including the 52--with additional atrio-ventricular connections. Arrhythmia was liquidated in 57 (93.4%) patients. Hospital lethality was 1.7%. PMID- 1942809 TI - [Modern methods of diagnosing and treating congenital pyloric stenosis in children]. PMID- 1942808 TI - [Anaesthesia in the surgical treatment of children in the "pediatric one-day surgery unit"]. PMID- 1942810 TI - [Histochemical diagnosis of Hirschsprung disease in newborns]. PMID- 1942811 TI - [A nomogram for the determination of transfusion therapy volume in children]. PMID- 1942812 TI - [Acute gangrenous perforated appendicitis complicated by rupture peritonitis and hemorrhage from Meckel's diverticulum]. PMID- 1942813 TI - [Diagnosis and treatment of congenital pyloric stenosis]. PMID- 1942814 TI - [Clinical aspects and surgery of fibrocholangiocytosis in children]. AB - Fifty one children with a diagnosis of fibrocholangiocystosis (FCC) were examined. A degree of circulatory blockade in the portal vein system in FCC was established to be one of the factors conditioning a severity of the course of the disease and its prognosis. With increase in duration of the disease and age of a child, the cirrhotic process in the liver and its complications are aggravating. The esophagogastric bleeding with the incidence as well depending on duration of the disease is the most severe and life-threatening complication. Our experience with operative treatment of FCC is indicative of the necessity to perform early interventions, and of a high effectiveness of creating the vascular anastomosis with preservation of the spleen. PMID- 1942815 TI - [Perforating stomach ulcer in a child with burns]. PMID- 1942816 TI - [Combination of acute intestinal invagination with abdominal injury in a child]. PMID- 1942817 TI - [Indirect endolymphatic antibiotic therapy in suppurative-inflammatory diseases in children]. PMID- 1942818 TI - [Aorto-esophageal hemorrhage in a child]. PMID- 1942819 TI - [Treatment of children with Morgagni-Adams-Stokes syndrome in congenital arrhythmia]. PMID- 1942820 TI - [Leiomyoma of the stomach in a child]. PMID- 1942821 TI - [Ways to improve the results of the treatment of acute obstruction of the aorta and major arteries of the lower extremities in middle-aged and elderly patients]. AB - The authors treated acute arterial obstruction in 190 patients. A complex of diagnostic and therapeutic measures, including the establishment of indications for operative treatment, development of tactics, use of ++physico-technical methods (ultrasound study, rheography, electrocardiography, ++roentgeno-contrast angiography, ultra-violet blood irradiation, electromyostimulation) was developed. A positive result of treatment was obtained in 78.9% of patients, incidence of an amputation performance was 13.7% lethality--12.6%. PMID- 1942822 TI - [Surgical treatment of combined occlusions of the aorto-femoral and femoro popliteal vascular segments in patients with severe ischemia of the lower extremities]. AB - The experience with surgical treatment of 107 patients with severe ischemia of the lower extremities, including 52 with associated lesion of the vessels of the aorto-femoral and femoro-popliteal segments, is summarized. A complex of preoperative and intraoperative assessment of regional hemodynamics was used. This permitted to avoid the amputation of an extremity in 86.6% of the patients. PMID- 1942823 TI - [Diagnosis and tactics in the surgical treatment of double aortic arch]. AB - Within the period of from 1978 to 1989, in 19 patients staying in the clinic, a double aortic arch (DAA) was diagnosed by means of roentgenologic investigation, esophagography, angiography. In comparison of the findings of esophagography and angiography, in 2 patients, atresia, of the left arch segment was revealed, in 9 patients, a double arch was associated with Fallot's tetrad (FT), in 4--with the interventricular septum defect (IVSD). All the patients were operated on. In 6 patients with isolated DAA, the lesser arch was transected: in 5--the left, in 1- the right one. In 13 patients with associated DAA and congenital heart defect (CHD), the simultaneous DAA transection and a palliative operation (in 9), or a radical correction of CHD (in 4) were performed. Two patients with FT 3 years later, underwent the second stage successful radical correction of a defect. A long-term result of treatment is good. PMID- 1942824 TI - [Reserve possibilities of creating the routes of collateral circulation in stenosing lesions of major arteries of the head]. AB - The analysis of complex examination of 54 patients with stenosing lesion of the major cephalic arteries by means of Doppler ultrasound, ultrasound scanning, carotid angiography, computerized tomography is presented. The most frequently, two ways of collateral blood flow--via the anterior communicative artery and via the branches of the external carotid artery were revealed. In the first case, ischemia of cerebral tissue is not pronounced, because the anterior communicative artery is functioning in change of a pressure gradient. The second way of collateral blood flow is less reliable, because it is developing slowly and do not provide adequate supply and normal functioning of the nerve cells. PMID- 1942825 TI - [Status of the celiac plexus in patients with extravasal compression of the celiac trunk and its role in the etiology of pain syndrome]. AB - The technique and results of surgical treatment of 109 patients with extravasal compression of the celiac trunk (ECCT), which in 77 patients was combined with a duodenal ulcer, are described. In the celiac plexus of the patients with ECCT, the inflammatory-sclerotic changes of a different degree of pronouncement were revealed. It was established that periarterial sympathectomy of the celiac artery and its branches had an essential effect on the state of gastric functions. In patients after isolated transection of a median phrenic ligament, the changes in gastric functions were not sharply pronounced. PMID- 1942827 TI - [Water-electrolyte balance in patients during operation on the aorto-femoral segment using various types of anesthesia]. AB - The indices of aqueous-electrolyte metabolism in patients, who underwent the reconstructive operations on the aorta, were studied. In patients with concomitant diabetes mellitus, a method of choice for anesthesia is an epidural anesthesia, with ischemic heart disease--combined epidural anesthesia. The most severe changes in electrolyte metabolism were noted after restoration of blood flow in blood loss of more than 10 ml/kg, under conditions of epidural anesthesia these shifts are less pronounced. PMID- 1942826 TI - [State of the crural musculo-venous "pump" in varicose veins]. AB - With the use of ultrasound flowmetry, retrograde popliteal and distal ascending phlebography, rheovasography and phlebotonometry, the functional state of ++musculo-venous "pump" of a crus in 53 patients with varicose disease was studied. The two degrees of impairement in the function of this formation, which are typical of complicated and non-complicated course of the disease, were established. Pronouncement of the impairement in function of musculo-venous "pump" of a crus directly depends on a degree of incompetence of the valves of the crural deep veins with vertical reflux of blood through them. PMID- 1942829 TI - [Pharmacological correction of disorders of antithrombogenic properties of the vascular wall in patients with arteriosclerosis of the lower extremities]. AB - Examined were 156 patients (all the men) at the age of from 41 to 76 years with obliterative atherosclerosis of the arteries of the lower extremities. The antithrombogenic properties of a vascular wall were studied with a use of the functional vascular test with arteriovenous occlusion (cuff test). Reduction of the antithrombogenic properties of a vascular wall, ++anti-aggregative, anticoagulative and fibrinolytic activity as compared with those in normal subjects was revealed. For correction of disorders in antithrombogenic activity of a vascular wall, the administration of a complex of hemostatically active preparations (trental, phytin, glutaminic acid) is recommended. PMID- 1942828 TI - [Diagnosis of concomitant ischemic heart disease and selection of surgical tactics in arteriosclerosis of major arteries of the lower extremities in relation to heart function in patients with extensive arteriosclerosis]. AB - The results of examination of 74 patients treated in the clinic for ischemia of the lower extremities with concomitant ischemic heart disease (IHD) diagnosed by the data of clinico-instrumental investigations are presented. In 10.8% of the patients, IHD was diagnosed in clinical examination, in 89.2%--in performing the loading test. The authors consider that the volume of intervention on the aorto iliac segment should correspond to a functional state of the myocardium, on the femoro-popliteal segment--to severity of a lesion at this region and is not restricted by functional state of the myocardium. To the patients with a functional reserve corresponding to a functional class IV, the performance of coronarography for definition of the expediency to perform one-stage intervention on the coronary bed and major arteries of the lower extremities is indicated. PMID- 1942830 TI - [Determining the limits of blood supply of vascularized skin flaps]. AB - On the basis of theoretical analysis of a problem and own anatomic investigations (41 preparation), the author has shown that a size of the axial cutaneous flap was determined by a sum of sizes of the true random flaps with a base situated on the axial vessels. An original concept for definition of the boundaries of guaranteed blood supply of the cutaneous vessels, algorithm for their designing and elevation have been developed. PMID- 1942831 TI - [Clinico-experimental evaluation of the new reconstructive operations on the popliteal and crural veins in postphlebitic syndrome during recanalization]. AB - The experimental data on studying surgical anatomy of the popliteal vein and its branches are presented. On the basis of the findings obtained, the experimental models of reconstructive operations--transposition of the small saphenous and muscular veins with the functioning valves to the position of a popliteal vein, its bifurcation or one of the sural veins--have been developed. The clinical assessment of the performed reconstructive operations on the veins of the popliteal -sural segment was carried out. The results of reconstructive operations are good. A conclusion about the expediency to use in the clinic of the developed methods of operative interventions on the major veins of the lower extremities was drawn. PMID- 1942832 TI - [Roentgeno-surgical treatment of vascular occlusive diseases of the lower extremities]. AB - The methods of direct revascularization of the lower extremities in occlusive stenotic lesion at the stage of severe ischemia were used in 144 patients. Of them in 35, simultaneously or with a several day interval, the ++roentgeno endovascular dilatation (RED) in the several segments of the arterial bed was carried out, in 36--RED was performed in combination with 2-3 procedures of plasmapheresis, in 16 patients in occlusion to a large extent, the isolated balloon profundoplasty was performed, in 46 patients with total lesion of the vessels--isolated RED of the aorto-iliac segment. This contributed to increase in the effectiveness of the collateral blood flow in the vessels of the lower extremities. A high effectiveness of the methods employed was noted in follow-up of from 1 to 5 years. The indications for the use of RED and causes of failures are presented. PMID- 1942833 TI - [Clinical aspects of using extremely high frequency electromagnetic radiation in the complex treatment of occlusive vascular diseases of the lower extremities]. AB - A method of local influencing with the extremely high frequency electromagnetic irradiation on the points of acupuncture was used in the complex treatment of 44 patients with obliterative diseases of the vessels of the lower extremities at the age of 34-75 years. Obliterative atherosclerosis was diagnosed in 15 of them, obliterative endarteritis --in 29. A high effectiveness of the method even in late stages of vascular pathology was noted. No complications were observed. PMID- 1942834 TI - [Surgical treatment of vertebrobasilar insufficiency]. AB - The results of surgical correction of blood flow in the vertebrobasilar basin in 58 patients ranging in age from 32 to 65 years were analysed. In 75.9% of cases, the disease was secondary to atherosclerosis. The tortuosity of the vertebral artery was noted in 12% of the patients. Transitory symptoms of ischemia were observed in 20.6% of the patients, chronic vascular cerebral insufficiency--in 53.6%, sequelae to the ischemic insult--in 25.8%. For diagnosis, the Doppler ultrasound, rheoencephalography, computerized tomography were used. The preference was given to extracranial operative interventions: +carotid-subclavian shunting was performed in 19, +intimo-thrombectomy from the subclavian and ostium of the vertebral artery--in 22, ++aorto-subclavian shunting--in 3 patients. Plasty of the vertebral artery was accomplished in 12 patients. The positive dynamics of neurologic status was noted in 91.3% of the patients. PMID- 1942835 TI - [Characteristics of blood distribution in the tissues of the lower extremities after lumbar sympathectomy]. AB - By means of a polarographic method, the peculiarities of blood distribution in the tissues of the lower extremities in 34 patients with obliterative atherosclerosis and in 29--with obliterative endarteritis after sympathectomy were studied. In successful intervention, the prognostically significant increase in oxygen tension in the muscles at the level of crura and feet was noted. It is suggested to use this test under conditions of medicinal ganglionectomy with the aim of prognostication of the effectiveness of the forthcoming lumbar sympathectomy. PMID- 1942836 TI - [Indications for performing lumbar sympathectomy]. AB - The results of treatment of 123 patients with obliterative diseases of the lower extremities, who underwent lumbar sympathectomy, and 115, who underwent the conservative therapy, were studied. The best result of sympathectomy was noted in patients with the impairement in the major blood flow and microcirculation without trophic disorders. In trophic disorders, sympathectomy contributed to reduction of a level of amputation. PMID- 1942837 TI - [Topographical and anatomical substantiation of the method of removal of small saphenous vein]. AB - The technique and data of stereoroentgenography of the small saphenous vein of 40 male and 10 female amputated and cadaveric extremities are presented. It was revealed that at a distance of 10-20 cm from the inter-articular fissure of the knee joint, the small saphenous vein had the greatest number of anastomoses and communicating veins. A method for removal of the small saphenous vein has been suggested. It was employed in 385 patients. PMID- 1942838 TI - [Treatment of trophic ulcers of the lower extremities using a magnetic field]. AB - The experience with treatment of 126 patients with ulcerous-necrotic lesion of the lower extremities of different genesis was summarized. A comparative evaluation of the effectiveness of treatment depending on a type of the magnetic field: the constant, alternating, or travelling impulse one was carried out. The most effective was the use of a travelling impulse magnetic field. The results of the investigation performed give grounds to recommend the wide use of magnetotherapy in the complex treatment of trophic ulcers of the lower extremities. PMID- 1942839 TI - [Diagnostic errors in thrombosis of the mesenteric vessels]. PMID- 1942840 TI - [A method of the treatment of chronic arterial occlusions of the lower extremities]. PMID- 1942841 TI - [A method of creating vascular anastomosis]. PMID- 1942843 TI - [A device for identification of the epidural space]. PMID- 1942842 TI - [A method of prosthesis in reconstructive operations on the aorto-femoral segment]. PMID- 1942844 TI - [A method of determining the level of amputation of the extremity in diabetic gangrene]. PMID- 1942845 TI - [Surgical treatment of heart injuries]. PMID- 1942846 TI - [Traumatic rupture of the descending portion of the thoracic aorta]. PMID- 1942847 TI - [Treatment of injuries of the superior mesenteric artery]. PMID- 1942848 TI - [Use of the compactotomy in acute thrombosis of the arteries of the distal segments of the extremities]. PMID- 1942849 TI - [A method of the preparation and training of a cutaneo-fascial flap]. PMID- 1942850 TI - [Treatment of combined injuries of the inferior vena cava]. PMID- 1942851 TI - [Gangrene of the left breast after thromboembolism of the branches of its internal artery]. PMID- 1942852 TI - [Extracorporeal connecting of porcine spleen in the treatment of post-splenectomy infection and thrombohemorrhagic syndrome]. PMID- 1942853 TI - [The first experience with the concurrent effect of YAG-neodymium and YAG-erbium laser on experimental animal tissues and the possibility of its use in surgery]. AB - To guarantee the necessary rate of cutting live tissues with adequate hemostasis along the line of the incision, the authors studied isolated and joint effect of radiations of AIG-neodymium and AIG-erbium lasers on the tissues of laboratory animals. The possibility of accomplishing intraoperative hemostasis on the parenchymal organs was studied in experiments with AIG-neodymium laser. A good dissection effect in cutting various tissues was produced in the second series of experiments with AIG-erbium laser. The simultaneous action of AIG-neodymium and AIG-erbium beams converged at one point on the surface of the biological object was studied in the third series of experiments. It was found that the effect ensures a good dissection of tissues with sufficient hemostasis. The results of dynamic morphological studies are shown. The possibility of using the device in surgery is discussed. PMID- 1942854 TI - [Treatment of fractures of long tubular bones in children using a compression distraction rod device]. AB - The article deals with the treatment of fractures of the long tubular bones in children by means of a rod device produced by the M. I. Sitenko Kharkov Research Institute of Traumatology and Orthopedics. It analyses some experience in the use of a compression-distraction rod device in 40 children (25 with fracture of the femur, 10 with fractures of the leg bones, 5 with fracture of the humerus). The advantages of rod devices over the other methods of treatment (pin apparatus, skeletal traction, intramedullary osteosynthesis) are shown, in the management of femoral fractures in particular. The authors consider the simplicity and easiness of the design and the possibility of rapid and bloodless installation and subsequent activation of the patient to be the main advantages of the rod device. The indications for application of the rod device were as follows: fractures which were difficult for reduction, open fractures, neglected fractures with the callus forming in improper position of the fragments, the need to perform an emergency operation on the viscera in polytrauma, delayed consolidation. Examples are given of successful treatment of patients 3 to 14 years of age. The method for applying the rod device is described as well as the possibility of expanding the volume of the reduction by using a reducing unit from the Volkov-Oganesyan apparatus together with a reducing unit from the apparatus. The possible complications which may occur in application of the apparatus and the means for overcoming them are discussed. PMID- 1942855 TI - [Hygromas of the wrist joint in children]. AB - The authors discuss their experience in the treatment of 45 children with hygromas of the wrist joint. Morphological and radiological studies confirmed the conception of the pathogenesis of hygromas which is based on that a hygroma is a transformed synovial capsule of the joint and the communication between them functions along the type of a valve. Problems of terminology and therapeutic tactics are discussed. The specific features of the operation and the results of treatment are described. The percentage of recurrences reduced from 15.4 to 7.7%. PMID- 1942856 TI - [Criteria for evaluating the severity of craniocerebral trauma in children]. AB - The article discusses the total results of multifactorial analysis of observations over 16,000 children with isolated and more than 400 with combined craniocerebral trauma (CCT) in the light of the peculiarities of the child age and the current trends in studying the problem in the Soviet Union and other countries. From these standpoints, the author first gives a clinicomorphological characterization of CCT types in children, deals with the methods and prospects of objectivication of the evaluation of the severity of isolated and combined CCT, extracranial local injuries in polytrauma, totally determining the severity of the general condition and the efficacy and prognosis of the diagnostic and therapeutic measures. Original methods for quantitative evaluation of the degree of severity of the trauma, which were developed in the clinic, are described. A variety of the clinical CCT forms and the possible variants of the concomitant injuries are systematized in a CCT classification approximated maximally to the solution of practical problems under different conditions, including extreme conditions in mass injuries. For this purpose, the author uses conventional designations for the main gradients of the pathophysiological reactions of the child's organism depending on the location and severity of the concrete damages and the general condition, making a coded recording of the diagnosis possible, which makes easier the sorting out and registration of the patients and orientation as regards the order in which aid should be given and the volume of the therapeutic and diagnostic programs with the use of computers. The patients were subjected to general clinical examination and laboratory tests, as well as special methods of examination (radiography, ultrasonic study, angiography, circulography, computed tomography, etc.). Importance was attached to the results of histological study and the reports of the forensic medical examination committee. PMID- 1942857 TI - [Early radical corrective surgery in congenital deformities of the lateral and posterolateral portion of the vertebrae]. AB - The article deals with the techniques of operation for semivertebra extirpation together with one-stage correction of the deformity with a contractor and anterior and posterior fixation of the spine. The operation was performed on 28 children as a result of which the spinal deformity was corrected, on the average, by 75% of the initial deformity in patients with scoliosis and by 50-66% in those with kyphoscoliosis. In 9 patients the initial deformity was corrected by more than 90%. Stable correction of the deformity was achieved in 84% of patients. The poor results (3 cases) were due to the use of a short compressing rod and erroneous choice of the material for spondylodesis. The operation is rekommended in progressing spinal deformities in young children under 3 years of age. PMID- 1942858 TI - [Organization of inpatient care on mass admission of children with burns suffered in a train crash]. AB - The article discusses some experience in organizing medical care for children injured during the crash in Bashkiria in June, 1989. Twenty-eight children with extensive Degrees II--IIIa, IVb burns were treated in the burn department of Children's Clinical Hospital No. 9, Moscow; 24 of them were discharged in a satisfactory condition, 4 children with a burn of more than 50% of body surface died. Simultaneous admission of the injured during a crash creates organizational, therapeutic, and psychological difficulties. The authors consider it necessary to create a special reserve of equipment, instruments, and drugs in the leading therapeutic centers, to train some of the general surgeons in problems of treatment of burn injuries, and engage, without fail, a psychoneurologist in the treatment. PMID- 1942860 TI - [Diagnosis and therapeutic tactics in torsion of the uterine appendices in girls]. PMID- 1942859 TI - [Treatment of acute hematogenous osteomyelitis in children]. AB - Experience in treatment of 348 children with acute hematogenic osteomyelitis is analysed. Newborn infants and children whose ages ranged from 1 to 15 years formed a group of patients. Of decisive importance in the outcome of the disease are early diagnosis and emergency operative measures, aimed at decompressing, opening and cleansing the purulent foci, producing a high concentration of antibiotics in the focus. Children who are in a grave condition are subjected to short-term preoperative management for 3-4 hours for detoxification, improvement of hemodynamics, prevention of septic shock and hyperthermia. Antibiotic therapy is given in 3 stages: in the first 10 days no less than 3 antibiotics are injected into the veins, into the muscles, and into the bones; from days 11 to 20 2 antibiotics are injected intramuscularly or into the bone; in the next 10 days one antibiotic is administered into the bone or muscle. Newborns and infants received injections by daily intraosseous puncture during the first 8-10 days of treatment. It is shown that the results of treatment may be improved only by intensive and complex measures applied timely and urgently. The mortality rate was 1.7% for the decade and 0.8% for the last 2 years. PMID- 1942861 TI - [Autotransfusion of ultraviolet-irradiated blood in destructive pneumonia of young children]. AB - Analysis of the results of clinicoimmunological study of the use of autotransfusion of blood treated by ultraviolet irradiation (ABUVI) in infants with acute purulent destructive pneumonia (APDP) revealed that imbalance of cellular and humoral immunity factors was the main factor determining the severity of the disease. ABUVI is an effective measure for correcting the immune response of the child's organism to the bacterial aggression through adequate production of monocytic phagocytes and plasma cells of the blood. It also influences the completeness of humoral immunity and reduction of T-lymphocyte deficiency in the acute phase of the disease. ABUVI raises the efficacy of complex treatment of toxicoseptic forms of APDR, reduces 1.7-fold the terms of treatment, and reduces considerably the mortality rate of this disease in young children. PMID- 1942862 TI - [Techniques of mechanical suture formation in Swenson's operation in children]. AB - The authors describe briefly the design and method of working with a special suturing instrument in formation of an extraperitoneal anastomosis by a modification of Swenson's operation in children suffering from developmental anomalies of the large intestine. The instrument ensures one-stage stitching of the intestine along its entire circumference before its resection. The anastomosis is formed four times more rapidly and the manipulation is more aseptic. Eight children were operated on with the use of the instrument and no complications occurred. PMID- 1942863 TI - [Method for creating colorectal anastomoses in children]. AB - A variant of two-stage formation of a colorectal anastomosis in children with Hirschprung's disease and megarectum is suggested. Low resection of the rectal ampulla and stitching of its muscular wall with the downwardly displaced area of the colon is conducted in the first stage. The second stage is performed 2 weeks later and consists in removal of the excess part of the intestine from the direction of the perineum. The operation was carried out on 23 children aged from 8 months to 13 years. No complications were encountered in the immediate postoperative period and in the long-term period. PMID- 1942864 TI - [Removal of giant trichobezoars of the stomach in children]. AB - The removal of trichobezoars of the stomach in children is discussed. This disease occurs as a rule in individuals with mental or some borderline abnormality which is attended by trichophagy and usually requires prolonged treatment. This determines the high probability of recurrent trichobezoar. With each repeated operation on the stomach in such cases the techniques become more and more difficult, injurious, and is a risk for the patient. All the known methods of endoscopic removal of bezoars cannot be used to remove trichobezoars because of their strength. The authors suggest a new endoscopic method by means of which trichobezoars of any size can be removed. It was successfully applied in the treatment of two patients with this disease who were thus free of an injurious operative intervention. PMID- 1942865 TI - [A method for intraosseous introduction of needles]. PMID- 1942866 TI - [Heat therapy in the comprehensive treatment of keloid scars with laser]. PMID- 1942867 TI - [Stomach cysts of the mediastinum in children]. PMID- 1942868 TI - [Double invagination of the intestines]. PMID- 1942869 TI - [Chronic ileocecal invagination after right hemicolectomy]. PMID- 1942870 TI - [Reconstructive surgery after chemical burns of the colon in children]. PMID- 1942871 TI - [Destructive appendicitis in a child with recurrent acute myeloblastic leukemia]. PMID- 1942872 TI - [Isolated pancreatic injury in children]. PMID- 1942873 TI - [Surgery in combined injury of the urinary bladder, urethra, rectum and fracture of the pelvic bones]. PMID- 1942874 TI - [Rare pathologic development of the scrotum in children]. PMID- 1942875 TI - [Mechanism of reflux and prevention of the pulmonary effects of aspiration after retrosternal colonoplasty for esophageal atresia in neonates and infants]. AB - The article discusses the causes of the development and prevention of gastrointestinal reflux in the early period after colonic retrosternal plasty of the esophagus in the newborns and infants. The mechanism of reflux linked with flotation of pleural sacs in the retrosternal tunnel, producing a pumping effect, is described. As a preventive measure the authors recommend postponing the cervical anastomosis for 12-14 days and forming a narrow retrosternal tuppel for the graft. Operations were conducted on 15 children, 3 of them died, one from massive reflux, aspiration, and asphyxia. PMID- 1942876 TI - [Primary peritonitis in children]. AB - The results of treatment of 219 children with "primary peritonitis" are analysed. Most patients (73.5%) were under 7 years of age. The simple form of primary peritonitis was encountered in 158 (72.1%) and the toxic form in 61 (27.9%) patients. Significant disorders of humoral (B-system) and cellular (T-system) immunity as well as combined incompetence of the neutrophil intra-leukocytic microbicidal system were revealed. In 72% of girls a relation was detected between the occurrence of primary peritonitis and the condition of maturation of the genitalia. All the children were treated by operation and recovered. PMID- 1942878 TI - [Sepsis in children (lecture)]. PMID- 1942877 TI - [Surgical treatment of appendicular peritonitis in children]. AB - The article is based on the results of 10-year use of the method of aspiration drainage of the abdominal cavity in the treatment of 980 children with purulent peritonitis of appendicular origin. The authors used only a polymer tube to drain the cavity of the true pelvis and in principle did not resort to intraoperative irrigation of the abdominal cavity, postoperative lavage, and intraperitoneal injection of antibiotics. Postoperative complications were recognized in the early stages of development and were treated by nonoperative methods on the main. The number of relaparotomies was 0.83% of the total number of operations for appendectomy. The described method meets the principles of pediatric surgery most fully, is more sparing than the other methods, and the authors recommend it for wide introduction into practice. PMID- 1942880 TI - [Quality of medical care for children with acute appendicitis]. AB - The expediency of appendectomy in 6% of cases was questionable. The increase of the quota of catarrhal appendicitis among all its forms reflected authentically the low quality of diagnosis in the hospital. To prevent needless appendectomies, the first 12 hours of hospitalization should be accepted as the maximally admissible period of observation over the child to make a decision concerning operative treatment. The persistence of a high incidence of appendicular peritonitis, despite the increase in the percentage of timely hospitalization, was evidently linked with the changed immune status of the child population. PMID- 1942879 TI - [Disorders of vital functions in acute peritonitis in children]. AB - Changes in vital functions in endotoxicosis were appraised in 41 patients with acute peritonitis during stages of intensive therapy in a complex fashion. Correlative relations were revealed between the severity of endotoxicosis and the function of blood circulation, blood gases, and respiration. Endotoxicosis was characterized by increased level of middle mass molecules, circulating immune complexes, leukocytic index of intoxication, asparagate and alanine transferase. Hemodynamics functioned in hyperdynamic regimen in the reactive stage of peritonitis, in the normodynamic regimen in the transitional stage, and in the hypodynamic regimen in the toxic stage. The immune status was inhibited in the toxic stage of peritonitis. Normalization of vital functions in the postoperative period occurred in parallel with decrease of the severity of endotoxicosis. The studied values approximated the average-age indices in patients with the toxic stage of peritonitis by postoperative days 7-10; sorption methods of detoxification were included in the complex intensive therapy measures in these children. PMID- 1942881 TI - [Formation of a urinary reservoir from a small intestinal graft in children with exstrophy of the urinary bladder]. AB - The authors suggest a new approach to the treatment of patients with exstrophy of the urinary bladder-the formation of an urinary reservoir from a detubulerized intestinal graft after II Kocks' method. This method, as well as its analogues, is mainly used in adults after radical cystectomy. Improved surgical techniques have been suggested on the basis of experimental works which allow the age features and the peculiarities of the functional condition of the formed reservoir to be taken into account. Analysis of the results of clinical use of the suggested method showed it to be effective in solving the problem of rehabilitation of patients with exstrophy of the urinary bladder, which allows it to be recommended as the operation of choice in the management of this developmental anomaly. PMID- 1942882 TI - [Surgical tactics in multiple obstructions of the urinary tract in children]. AB - One the basis of the results of surgical treatment of 84 children the authors identified 5 main groups of multiple obstructions: 1) obstruction of the vesicourethral segment in combination with obstructions of segments located above -37 (44.1%) patients; 2) unilateral obstruction of the ureterovesical and ureteropelvic segments--11 (13.1%) patients; 3) bilateral obstruction of the ureterovesical segments--19 (22.6%) patients; 4) bilateral obstruction of the ureteropelvic segments--11 (13.1%) patients; 5) other variants of obstructions of the ureterovesical and ureteropelvic segments--6 (7.1%) patients. It was established that urodynamic disorders conducive to the occurrence and progress of chronic pyelonephritis in multiple obstructions of the urinary tract in children are determined not only by the nature of congenital morphologic changes in the urodynamic segments, but by the features of their functions, interaction, and mutual influence, which should be taken into account in choosing the tactics of surgical intervention. In combination of obstruction in the vesicourethral segment, as well as in the ureterovesical segments, operative treatment should be started on the vesicourethral segment because urodynamics in the ureterovesical segments in children under 3 years of age may become normal without a surgical intervention on them. Correction of obstruction in the ureterovesical segment facilitates restoration of urodynamics in the ureteropelvic segment in unilateral obstructions, which determines the sequence of the operative intervention. PMID- 1942883 TI - [Electrophysiologic diagnosis of neurogenic bladder in children with myelodysplasia]. AB - Ninety-seven children with neurogenic bladder and myelodysplasia were subjected to complex examination. The somatic innervation of the sphincter urethrae externus and sphincter ani muscles was appraised by the method of sacral guided reactions by a CT-01 electromyograph and by an original method consisting in registration of the reflex response of the named anatomical structures according to the fluctuations of the intraurethral and intraanal pressure. It was established that maintained, partly disturbed, and absolutely absent somatic innervation of the sphincters of the bladder and rectum is encountered in patients with myelodysplasia. The more the innervation of the sphincters disturbed is, the more the urinary bladder is excluded from the "accumulation evacuation" urodynamic cycle and the lesser the probability of disorders of urodynamics of the upper urinary tract is, and vice versa. The obtained information is important in choosing the therapeutic tactics for patients with a neurogenic bladder. PMID- 1942884 TI - [Endourethral correction of valvular obstruction in children]. AB - Endourethral dissection of valvular cusps was carried out by means of an urethrotome in 34 boys with Type I and III valves of the posterior urethra. The indications for and the techniques of the dissection on depending on the type of the valve are discussed and measures for preventing complications are suggested. Endoscopic, radiological, and urodynamic methods of examination of the lower urinary tract determined the therapeutic tactics and help in evaluation of the efficacy of the operative treatment. The method allows correction in patients with valves to be performed in one stage in the compensated stage of the disease and after preliminary derivation of urine in the decompensated stage. The authors recommend optic urethrotomy for the treatment of children with valves of the posterior urethra. PMID- 1942885 TI - [Morphofunctional immaturity of the urinary tract and vesicoureteral reflux in young children]. AB - On the basis of rich clinical experience--593 patients and 916 renoureteral units (RUU) with vesicoureteral reflux (VUR) in infants the authors showed that early recognition of VUR is necessary, which is ensured by adequate organization of service to infants of the "risk group". Complex examination of children by functional diagnostic methods conducted under general anesthesia makes it possible to undertake some methods of examination for the detection and control of morphofunctional immaturity, while early application of purposeful rehabilitation measures in the stages inpatient treatment--outpatient treatment- treatment in the family produces a "positive dynamics" of the course of the pathological process in most patients (up to 82.1%). All this in complex confirms that morphofunctional immaturity of the urinary tract is the main cause of VUR in infants. PMID- 1942886 TI - [Cysts of the common bile duct in children]. AB - From 1975 to 1989 operations were carried out in the clinic by various methods on 30 children with cysts of the common bile duct. Hepaticoor choledochojejunostomy after Roux is the operation of choice in cysts of the choledochus. However, recurrent cholangitis caused by jejunobiliary reflux was encountered in some patients in the postoperative period. The accumulated clinical experience has also shown that the Roux type operation does not guarantee a successful functional result. To prevent reflux of the intestinal contents into the biliary tract after Roux's anastomosis, the authors used an antireflux valve on the excluded loop of the jejunum. Experimental study was undertaken of the theoretically substantiated antireflux valve on an excluded loop of the type of a "nonspilling inkpot" with a shortened loop. The creation of an antireflux valve in the form of an invaginated segment prevents jejunobiliary reflux and therefore provides the possibility for reducing significantly the length of the excluded loop in Roux's biliodigestive anastomoses. The obtained positive results confirm the rationality of this construction which does not need additional time for the operation. Since 1987 four children have been operated on by this method in the clinic. The length of the excluded loop was reduced from 30 to 15 cm. Postoperative complications linked with reflux into the biliary system were not encountered. PMID- 1942887 TI - [Diagnosis and surgical treatment of solitary large and giant hydatid cysts of the liver in children]. AB - The article analyses the results of surgical treatment of 33 children with solitary large (16) and giant (17) hepatic cysts in the stage of preperforation. Most of the cysts (18) were located in the subdiaphragmatic region. If the method of ultrasonic examination (USE) is available and bearing in mind the grave general condition, extended radiological methods of examination are not advisable for establishing the diagnosis. An emergency operative intervention is undertaken by wide laparotomy with transverse section of the anterior abdominal wall. The residual cavity is liquidated by turning inside a part of the fibrous capsule (7), filling it with the omentum (10). In 4 patients the residual cavity was drained with prolonged active aspiration. Large dense areas of fusion of the fibrous capsule with other organs should be left as islets. There were no fatal outcomes. PMID- 1942888 TI - [Serum immunoglobulins in the assessment of pulmonary inflammatory processes in children]. AB - The article discusses the information on the level and dynamics of serum immunoglobulins (Ig) in 48 children with acute pneumothorax (AP) which complicated acute respiratory virus infection and destructive pneumonia. Analysis of the results showed that appraisal of the Ig level with consideration for the terms of the development of the disease and the generally accepted laws of the formation of the immune response makes it possible to evaluate objectively the patient's condition, the degree of the inflammatory process and the destruction of the pulmonary tissue, establish the time of the development of the complication, predict the course and outcome of the process, and appraise objectively the results of treatment with immune agents in a complex of therapeutic measures. PMID- 1942889 TI - [Functional condition of the liver after surgical treatment of cirrhosis in children as revealed by hepatoscintigraphy]. AB - Scintigraphy with colloid 99mTc (56 cases) and the radiopharmaceutical preparation 99mTc--HIDA (43 cases) was performed in children with early and developed cirrhosis of the liver to study the functional condition of the hepatic Kupffer's and parenchymal cells in the long-term periods after surgical treatment. Increased activity of the parenchymal cells and inactivation of Kupffer's cells were revealed after splenectomy. The formation of a portocaval shunt and denervation of the hepatic artery promoted activation of hepatocyte functioning in these patients. PMID- 1942890 TI - [Osmolality of contrast media--a risk factor in radiological endovascular procedures in children]. AB - The study was conducted in 90 children aged from 5 months to 14 years during radiologically-guided endovascular (RIV) interventions with bolus injection of radiocontrast agents (RCA) in a dose of 2-3 ml/kg for 2-3 sec. High-osmolality RCA were used in 80 children, an nonionic low-osmolality RCA omnipaque-300 in 10 children. Injection of RCA bolus was attended by marked acute disorders of blood colloidoosmotic equilibrium (COE) which depended on the initial status of the latter and were greater when high osmolality RCA were used. On the basis of the study results, the authors developed and tested a method of modulator infusion therapy with consideration for the initial blood COE (hyper-, normo-, hypoosmolality). The suggested therapy makes it possible to reduce the degree of blood COE disorders considerably and prevent the development of complications associated with disturbed osmoregulation. PMID- 1942891 TI - [Electroanalgesia in the postoperative period in children]. AB - The object of the work was to appraise clinically the efficacy of electroanalgesia in the postoperative period in children and study the effect of this type of anesthesia on the vital functions of the organism. The purpose of special studies was to objectively reflect the response of central hemodynamics and neurovegetative state as a response to postoperative stress, pain is the main factor. The conducted complex studies showed that the application of transcutaneous electroneuro-stimulation for postoperative analgesia in minor operative interventions activates the antinociceptive system sufficiently rapidly, stabilizes cardiovascular activity and the activity of the sympathetic and parasympathetic parts of the autonomic, nervous system. The information obtained bears evidence that when applied in minor operative interventions the method is an adequate alternative of postoperative medicamentous analgesia in children. PMID- 1942892 TI - [Repair of ventricular septal defects with pericardial xenografts in infants]. AB - The article deals with the experience in the clinical use of pericardial xenografts in surgical correction of large ventricular septal defects in babies. Primary closure of the VSD under conditions of hypothermic perfusion at a low volume rate was carried out in 202 children whose ages ranged from 6 weeks to 12 months and body weight from 3.5 to 10 kg. The aorta was not clamped. In 142 patients the defect was closed with xenogenous pericardium treated with 0.6% glutaraldehyde solution on HEPE buffer and 1% sodium dodecyl sulfate solution. A pericardial xenograft treated by Carpantje's method was used before 1985 (59 patients). The hospital mortality rate was 6.4% (13 patients). The mortality rate was 5.1% among patients over 6 months of age and 11% among those under 6 months of age, which is explained by their initially extremely grave condition. The long term results were studied in 133 patients by bidimensional and Doppler echocardiography. The pressure in the right ventricle was found to be normal (26 +/- 4.3 mm Hg) in all patients. The right- and left-ventricular end-diastolic volumes were normal, just like the ejection fractions (55.4 +/- 6.6 and 57.3 +/- 6.8%, respectively). A small escape of blood at the level of the graft was found in only 5% of patients. Mild incompetence of the tricuspid valve without clinical manifestations was revealed in 18% of patients. In none of the cases, signs of calcinosis or aneurysm of the graft were found, fatal outcomes in the long-term postoperative periods were not encountered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942893 TI - [Comparative evaluation of various methods for feeding children with pyloric stenosis]. AB - Pylorostenosis is still the most frequently encountered type of congenital intestinal obstruction. A severe course of the disease with a fatal outcome is observed today. Successful treatment is linked in many respects with adequate feeding of the patient. The authors examined and performed operations on 90 children. According to the type of feeding they were divided into 3 groups. Group 1 consisted of patients given the generally accepted oral diet in portions, group 2 was made up of infants fed according to a "forced" schedule (the physiological requirements were supplied by the natural way by the 3rd-4th postoperative day), and group 3 received enteral feeding through a tube. The tube was introduced by means of an endoscope before or during the operation. It was found that in feeding through a tube children with pylorostenosis could be given 2-3 times more milk before the operation and in the first days after it. Regurgitation and the phenomena of esophagitis and jaundice are arrested in this case. The gain in weight is 3 times that in children of group 1. The authors consider this type of feeding to be justified in gravely ill patients. The "forced" schedule is used in an uncomplicated course of the disease. Feeding of infants with pylorostenosis by the generally accepted method was found to be unsatisfactory and the authors rejected it. PMID- 1942894 TI - [The surgical correction of an ostium secundum defect in the interatrial septum]. AB - The operation of choice for correction of secundum type atrial septal defect is cardiopulmonary bypass. Combination of atrial septal defect with partial anomalous pulmonary venous drainage is considered absolute indication for bypass operation. The authors apply an original method for closure of the defect without resorting to bypass. For a period of seven years they have operated 240 patients from 3 to 54 years of age. Eighty four patients have been operated by the covered method of professor Zorin and in 23 correction of venous sinus defect was performed. PMID- 1942895 TI - [The anesthesiological-resuscitation and surgical problems in a female patient with an adrenal cortex carcinoma]. AB - A patient has been observed with virilizing cancer of the adrenal cortex. Anesthesiologic-resuscitation and operative problems are discussed. The importance of corticosteroid substitutional treatment is emphasized. The operation was performed through transversal laparotomy under classical neuroleptanesthesia. PMID- 1942897 TI - [2 clinical cases of cholelithic ileus]. PMID- 1942896 TI - [A case report of Peutz-Jeghers syndrome in childhood]. AB - The clinical course, diagnosis and treatment of Peutz--Jeghers's syndrome in childhood are discussed and a case reported in a eight-year-old girl. The disease presented with skin and mucosal melanin pigmentation in the mouth, frequent colic like abdominal pain, due to chronic recurrent invaginations. On operation, the cause of the invaginations appeared to be 11 polypous formations in small intestines (8) and in the large intestines (3), which were subjected to radical operative removal. For an observation period the child had no complaints and was clinically healthy. PMID- 1942898 TI - [The potentials and limits of thoracic epidural anesthesia in abdominal surgery]. AB - A general clinical assessment was made of the possibilities and limits of thoracic epidural anesthesia (TEA) in 132 abdominal operations. The technique applied for preparation, the performance and induction in anesthesia, the intraoperative observation and the postoperative analgesia are described. The patients were evaluated according to ADA for risk factors and the accompanying diseases, the diagnoses by groups and the operations performed on the bile ducts, the small and large intestines, the liver, the retroperitoneal organs, combined operations, interventions on the anterior abdominal wall etc were presented. The mean duration of the operations was 111.77 min., the preoperative preparation and performance of anesthesia--63 minutes, total 175 minutes. Application of TEA was decided taking into consideration the patient state, the type of operation the alternative for applying general intubation anesthesia, the course of anesthesia and the postoperative analgesia. The hemodynamic changes especially in cardiac patients, other complications and causes of inadequate effect of TEA in 12 cases not included in this report are discussed. As a rule, appendicectomies and inguinal herniotomies were not included also in this report. PMID- 1942899 TI - [Pancreatic cancer. I. The age distribution and location of the tumor process in the gland (a statistical analysis based on autopsy data from the Department of Pathological Anatomy of the Biomedical Research Institute over the 25 years from 1963-1987]. AB - The age distribution and localization of the neoplastic process in the pancreas was analyzed. Cancer of the pancreas was most common in the age from 41 to 80 years of age, with a peak in the sixth decade. A study of the anatomical localization of the tumor in the gland, purposely carried out, demonstrated that the head of the pancreas was the most common site of the tumor, with the body and tail ranking next. PMID- 1942900 TI - [Pancreatic cancer. VII. The incidence and characteristics of the metastasis of pancreatic adenocarcinoma]. AB - The study demonstrated that adenocarcinoma was the most common form of pancreas cancer. In the majority of cases it originated from the head of the gland, with the body ranking second and the tail third. Adenocarcinoma most frequently metastasized in the lymph nodes, less in the liver and rather infrequently in the lungs and intestines. When the cancer involved the entire gland or a greater part of it, metastases in the latter organs were practically obligatory. Most frequently metastases of pancreas adenocarcinoma were observed in the seventh decade, followed by the sixth and the eighth decades. This regularity as a whole matched the regularity of the age prevalence of pancreas cancer. PMID- 1942902 TI - [Injuries to the large vessels in the abdominal area]. PMID- 1942901 TI - [Neoplasms following kidney transplantation]. AB - The incidence, predisposing factors, localization, evolution and outcome of neoplasms following kidney transplantation were studied in two groups of patients -120 and 146 patients for an observation period from 1 to 16 years. In patients with adequate renal function who received immunosuppressive treatment for more than one year (accordingly 78 and 88 patients) neoplasms developed in 4 and 10 patients with mean duration of immunosuppressive treatment 4.9 and 6.1 years respectively. The neoplasms were: 3 skin cancers, 2 lung cancers, 2 Kaposi sarcomas, 1 lymphosarcoma, 1 breast cancer, 1 prostate cancer, 1 renal cancer, 1 rectal cancer and 2 polyps of the colon. The case fatality rate was 3.6 per cent. The importance of precision of the immunosuppressive treatment for reducing the incidence of these complications is pointed out. PMID- 1942903 TI - [The complications of the polycystic kidney requiring surgical treatment]. AB - The complications--incidence, relation with renal function and treatment--and the results of treatment are analyzed in 87 patients with autosomal-dominant polycystic disease of the kidneys. Complications requiring surgical management developed in 16 patients (18.4 per cent). In 8 patients there was infection of cysts, 3 had obstructive calculous uropathy and the rest--other complications. Nine patients were operated. In patients with suppurated cysts the surgical method of choice was excision of the cysts and ignipuncture. Taking into account the significantly higher incidence of infections in patients on hemodialysis (p less than 0.05), the ultimate results of treatment are evaluated as very good- control of the septic state, no case fatalities. PMID- 1942904 TI - [Primary malignant non-Hodgkin's lymphoma of the large intestine]. AB - A case is reported of primary malignant non-Hodgkin's lymphoma of the colon of a 85-year-old woman. The clinical manifestations and the X-ray pattern were those of cancer. The diagnosis was established on post-mortem examination. Histologically this was a centroblastic-centrocytic lymphoma of Brill-Symmers with low-grade malignancy. The clinical, diagnostic, prognostic and therapeutic problems in malignant non-Hodgkin's lymphomas of the colon are discussed. PMID- 1942905 TI - [The surgical treatment of congenital hydronephrosis]. AB - Experience is recorded with the operative treatment of congenital hydronephrosis in 56 patients, 14 to 59 years of age, over the period from January 1985 through July 1989. Of major importance for establishing correct diagnosis were excretory urography and ultrasound examination of the kidneys. Retrograde ureteropyelography was performed in only 5 patients on the operation day. Constrictions in the area of the pyeloureteral segment were the most common cause of hydronephrotic transformation of the kidneys. Because of the encouraging results, the authors give preference to the plastic operation by the method of Anderson-Hynes with drainage of the urine through nephrostoma and intubation drain for a period of 12 to 15 days. Operations for congenital hydronephrosis consisting only of removal of the adhesions in the area of the pyeloureteral segment are not advised. PMID- 1942906 TI - [The tumor markers CEA and CA-19.9 in patients with colorectal carcinoma]. AB - The levels of two tumor markers--CEA and CA-19.9 were repeatedly determined in 146 patients with histologically verified colo-rectal cancer and in 58 healthy controls. The normal CA-19.9 values were up to 30 U/ml. The sensitivity of the two markers proved to be low: 48.8 per cent for CEA and 37 per cent for CA-19.9. In 26 of 35 patients with local recurrence or metastases marker increase preceded the appearance of clinical symptoms of progression of the pathologic process. The two markers appeared more informative than each of them when separately determined. PMID- 1942907 TI - [The microsurgical treatment of lymphedema of the extremities]. PMID- 1942908 TI - [The use of tumor markers in hepatogastroenterology]. PMID- 1942909 TI - [A case of mesothelioma]. PMID- 1942910 TI - [Atypical anatomical variants and anomalies of the biliary tract in patients with biliary tract and pancreatic diseases. II. Endoscopic treatment]. AB - Results are reported of endoscopic treatment of 79 patients with atypical anatomical variants and anomalies of the bile ducts: common bile duct calculosis (54), stenosing papillo-odditis (8), indurative pancreatitis (2) and bile duct cancer (15). The following endoscopic manipulations have been performed: endoscopic sphincterotomy (72); hydrostatic balloon extraction of calculi (27); hydrostatic balloon dilatation of constricted segments (29); mechanical lithotripsy (15); nasolabial drainage (17) and endoprosthesis (15). Much more difficult was the extraction of calculi from the common bile in the event of atypical anatomical variants and anomalies of the distal portion of the common bile duct (chi 2 = 14.55; p less than 0.001). Treatment resulted in significant reduction of the bilirubin levels (t = 4.13; p less than 0.001), of AP (t = 4.47; p less than 0.001), GGTP (t = 4.07; p less than 0.001); AcAT (t = 5.75; p less than 0.001) and AlAT (t = 5.63; p less than 0.001). Complications occurred in 6 per cent of the patients (acute pancreatitis, cholangitis, hemorrhage). Mortality from endoscopic treatment was 1.3 per cent. Endoscopic methods for treatment are advised as alternative to operative treatment for patients in advanced age and high operative risk. PMID- 1942911 TI - [2 cases from the practice of intensive treatment]. AB - Two cases from the intensive treatment practice are presented: Case I--a 43-year old woman drawn out from a state of clinical death during chronic dialysis for chronic renal failure with importunate ultrafiltration to combat the severe pulmonary edema, which led to hypoxia and cardiac arrest with functionally affected hemodynamic parameters (central venous pressure), because of centrally placed a/v fistula. Case II--a 46-year-old woman with severe drug disease and extremely critical hypotonic hyperhydration and anasarca, treated also with ultrafiltration, enhanced sodium influx and intensive application of diuretics; for 24 hours a negative fluid balance was achieved (71191 ml) until finally a relative fluid-electrolyte equilibrium was reached. PMID- 1942912 TI - [An instrument for bile duct tunneling and endoprosthesis in cancer of the hilus of the liver and biliary tract]. PMID- 1942913 TI - [Experimental studies of retinal ultrastructure after administration of highly fluorinated alkane into the vitreous body]. AB - In experimental investigations the hydrogen-fluoroalkane was introduced into the rabbit vitreous and subsequently the retina was examined in the electron microscope. The observations were carried out in 1, 4 and 8 weeks after introduction of the compound. It was demonstrated that the fluoroalkane penetrated into the internal retinal layers. These layers showed the presence of macrophages, the cytoplasm of which indicated the absorption of the compound. The structure of the retina was preserved till the end of the observation. The compound did not exert any toxic action. PMID- 1942914 TI - [Changes in gas metabolism in the anterior chamber during the treatment of experimental uveitis]. AB - Examined was the dependence of the pH of the aqueous, the oxygen pressure pO2, the pressure of CO2, the content of bicarbonate ions--HCO3- and the balance of energy--from the intensity of uveitis provoked experimentally in rabbits by application of 5 mg of albumin fraction of the cattle protein treated by topical cortisone. It seems that the physicochemical indexes and the energy balance may be an essential source of information of the intensity and character of the process of uveitis. Their normalization proceeds together with the improvement of the clinical condition of the examined eyes. PMID- 1942915 TI - [Value of studying the intraocular pressure in patients operated on for retinal detachment]. AB - The IOP was checked in 263 eyes operated for retinal detachment--before, during and after surgery. Statistically lower values of the IOP were observed in eyes with retinal detachment in comparison with the healthy fellow-eye and in cases with an extensive and prominent detachment. There was no interdependence between the values of the IOP--even showing considerable oscillations--and the occurrence of complications, the normalization of the postoperative IOP and the results of the treatment. The measurements of the IOP in the course of retinal detachment operation may have a significance in determining the indications for a drainage of the subretinal fluid and in evaluation of the degree of the retinal invagination. PMID- 1942916 TI - [Pupillography in unilateral retinal detachment]. AB - The reaction of the pupil for light was checked in 25 patients with an unilateral retinal detachment. The sore eye and the fellow-eye were examined separately. The deterioration of the reaction was dependent on the area of detachment and on the condition of the macula. PMID- 1942917 TI - [Double-blind method of using solcoseryl ophthalmic gel and 2,4% cysteine in ophthalmic gel in patients with chronic recurrent keratitis and keratitis sicca]. AB - A double blind study with Solcoseryl compounds in ophthalmic gel and with 2.4% cystein in ophthalmic gel was performed in the period 1985-1988; it was used in 18 cases: with chronic recurrent keratitis (11 patients) and sicca keratitis (7 patients). Observed was the influence of these compounds on the epithelialization of the cornea, on the improvement of corneal transparency, the diminutation of the troubles connected with dessication of the eye in sicca keratitis. In spite of the small number of cases the observations were interesting. In patients with a chronic recurrent keratitis the influence of both compounds showed to be beneficial for the condition of the cornea. In patients with keratitis sicca one could observe a better tolerance of the Solcoseryl ophthalmic gel which could be applied for a longer period in comparison with cystein in gel. PMID- 1942918 TI - [Personal experience and the results of surgical treatment of blepharoptosis]. AB - The authors discuss the indications for the operation, the surgical technique and results obtained in 92 patients who have been operated for ptosis (109 operations) by the modified method of Berke and Neuhaus. From the experience of the authors it appears that the best approach is a subciliary one especially in congenital ptosis. The Neuhaus method showed to be successful in patients with ptosis connected with the "jaw-winking" Marcus-Gunn phenomenon; in these patients one obtained the elevation of the upper lid and liquidation of the synkinesis. RESULTS: in congenital unilateral ptosis very good result was achieved in 63 p.c., a good one in 32.3 p.c., a poor one in 4.8 p.c. In bilateral ptosis very good result could be achieved in 36.8 p.c., a good one in 52.5 p.c. and a poor one in 10.6 p.c. of cases. Insufficiency of the lid closure as a principal complication of operation was seen in 6 patients (6.5 p.c.) without any consecutive pathological changes in the eye. PMID- 1942919 TI - [Use of the Miragel acrylate sponge in severe eye burns caused by lime]. AB - One of complications of burns of the eye caused by lime are the conjunctival adhesions. Presented are 2 patients who were treated by strips of Miragel acrylate sponge implanted temporarily into the conjunctival sac. After 1 year of observation and removal of the implants the conjunctival sac showed to be free of adhesions with a free motility of the eye. PMID- 1942920 TI - [Optical correction of keratoconus by soft contact lenses]. AB - Soft contact lenses have been used in 41 patients (71 eyes) aged 10-50 years with uni- and bilateral keratoconus. In 46 eyes (64.8 p.c.) application of soft contact lens enabled visual acuity of 5/5 to 5/25, mainly in initial or intermediate phases of keratoconus. In these cases correction with soft contact lenses gave better results than after application of ++sphero-cylindrical spectacles. In far advanced keratoconus one can observed better visual acuity after application of soft contact lenses in comparison with spectacles correction. However correction with hard contact lenses was the best one. PMID- 1942921 TI - [Lacrimal duct obstruction in newborn infants]. AB - Presented is the personal experience concerning the early opening of the occluded lacrimal passages. In 149 newborn babies 4-5 days of age the author performed- according to indications--the syringing and probing of the lacrimal passages with a full success. PMID- 1942922 TI - [Diagnosis and etiopathogenesis of retinitis in patients with multiple sclerosis]. AB - Presented are: the incidence, symptomatology and diagnostics together with electroretinography of retinal periphlebitis as well as retinitis and maculopathy in patients with multiple sclerosis. Particular attention is called to the histopathology of the retina in this disease. The etiopathology of retinitis and maculopathy in multiple sclerosis is still unknown. Four etiopathological hypotheses are shortly discussed. PMID- 1942923 TI - [Congenital genetically determined retinal detachment]. AB - The authors discuss the typical signs and symptoms of congenital retinoschisis: splitting of the retinal layers in the macular and equatorial regions and vitreous changes. They describe the evolution of these changes and their complications. PMID- 1942924 TI - [Congenital retinal detachment with predominant macular changes]. AB - The authors call attention to the existence of incomplete forms of retinoschisis and some forms with predominant macular changes which may erroneously be treated as Stargard's disease. A correct diagnosis is essential because of the necessity of a systematic control of the fundus periphery. Discussed are the possibilities of prevention and treatment of complications such as haemorrhages and retinal detachment. PMID- 1942925 TI - [Hallermann-Streiff-Francois syndrome]. PMID- 1942926 TI - [Results in Pediatric Oncology 15. Reports of the Society of Pediatric Oncology and of the German Work Group for Leukemia Research and Therapy in childhood]. PMID- 1942927 TI - [Recommendations for the structure and equipment of pediatric oncologic centers]. AB - The yearly incidence of cancer in children and adolescents within Germany is about 2200. The regular medical care for these children is effected within prospective multicenter trials of the DAL and GPO respectively. These trials achieved excellent results and gained high international reputation. Following an initial funding by the Bundesministerium fur Forschung und Technology the continuation of these trials nowadays is fully dependent on private third parties financial aid especially from the Deutsche Krebshilfe. Guarantee of progress in clinical research and of improvement in patient care as well is closely related to establishing pediatric cancer centers. Accruing about 80 new patients per year such centers have an optimum size justifying establishing stabile substructures. Integrated basic research and organization of special clinical domaines need a differentiated structure of management and a sufficient number of qualified personnel in time nonlimited positions. The recommendation of the Arbeitsgemeinschaft Deutscher Tumorzentren from 1979 for personnel equipment is largely insufficient with respect to the inpatients nursing staff for pediatric oncology units. A basic equipment of 1.75 nurses per patient and additional nursing staff with specific functions would seem appropriate as demonstrated by analyses and calculations within the last part of our recommendations. The ADT recommendations are also insufficient with respect to secretaries and documentation assistants. Concerning the physicians staff the ADT recommendations just need an adaption to the changes in working time in accordance with the tariffe. These recommendations, however, urgently need to be realized. The necessary staff for psycho-social work has been incorporated into our recommendations for the first time. The ratio of patient rooms to function rooms (excluding laboratories) in pediatric oncology centers diposing of an outpatient area and a day clinic should be about 1:3. Deficiencies in the personnel equipment and the generally pronounced lack in function rooms as well are hampering the daily work and have negative impact on the quality of care as experienced by the patient on the safety of medical and nursing practice and on the quality of teaching, medical education and advanced training. PMID- 1942928 TI - [Treatment of soft tissue sarcomas in childhood and adolescence: results of the CWS-81 multicenter therapy study]. AB - 344 previously untreated patients, under 19 years of age, with soft tissue sarcoma (STS) entered the first German STS Study, CWS-81. 218 of them with chemosensitive STS (Group A: rhabdomyosarcoma [RMS], synovial sarcoma, extraosseous Ewing's sarcoma, undifferentiated sarcoma and malignant peripheral neuroectodermal tumor) were evaluable for this analysis after a minimum potential follow-up of 6 years. A staging system based on the extent of disease, defined post-surgically, was used. The chemotherapy for stages I-III (VACA cycle) consisted of vincristine, dactinomycin, cyclophosphamide and doxorubicin. Patients with metastatic disease as well as stage III patients who failed to respond to VACA, were given ifosfamide instead of cyclophosphamide. The definitive local tumor control procedure for patients in stages II-III depended upon the tumor status at second-look surgery after 16 weeks of chemotherapy (no irradiation, 40Gy or 50Gy). The DFS rate after 5 years for group A was 57 +/- 4% and for patients with non-metastatic tumors (Stages I-III), 69 +/- 4%. There was no difference in prognosis between stages I and II (DFS rate 88 +/- 5% and 88 +/- 6% respectively). The DFS rate for stage III was 54 +/- 5% and for stage IV, 11 +/- 5%. Lack of local tumor control was the main cause of therapy failure: 10% of patients with localized disease never achieved CR, 18% relapsed locally. The most important prognostic factors were tumor size (p = .0002) and the degree of tumor regression after primary chemotherapy (p = .02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942929 TI - [Neoadjuvant chemotherapy of osteosarcoma. Preliminary results of the cooperative COSS-86 osteosarcoma study]. AB - The neoadjuvant study COSS-86 was undertaken aiming at (1) improving the cure rate in osteosarcoma by early intensification of chemotherapy in high risk patients and (2) investigating the effect of intraarterial (i.a.) versus intravenous (i.v.) administration of cisplatinum. (1) Ifosfamide was added to the well proven drugs in osteosarcoma such as doxorubicin, high-dose methotrexate and cisplatinum in patients with large tumor size or/and high portion of chondroid groundsubstance or/and scintigraphic nonresponse after 4 weeks of preoperative chemotherapy. It was given in combination with cisplatinum. (2) The same patients were allocated to either the intraarterial study arm or the intravenous control arm of the study. The response rate (greater than 90% tumor necrosis) of all patients was 75% (88/118). No advantage in response rate was achieved by i.a. infusion of cis-platinum within this highly efficient 4-drug regimen (i.a. 75% (33/44) vs. i.v. 74% (35/47)). The significantly improved response rate in this study results in a better metastasis free survival (MFS) of 77% (+/- 4) at 4 years. PMID- 1942930 TI - [Initial response to therapy as an important prognostic factor in acute lymphoblastic leukemia in childhood. COALL study group]. AB - Prognostic factors to estimate the risk of relapse are crucial for risk-adapted therapy in acute lymphoblastic leukemia (ALL). In a cooperative multicenter treatment study for childhood ALL (COALL-03-85) the prognostic relevance of the bone marrow (BM) blast count at day 28 was evaluated. Treatment was adjusted to the initial risk factors; patients with high risk (white blood count (WBC) greater than or equal to 25/nl, age greater than or equal to 10 years, T- or NULL ALL) received intensified therapy consisting of rotation of 6 non cross-resistant drug combinations with 12 different agents. After 4 weeks 289/305 (94.8%) children were in complete remission (CR); one child died of infection, and 15 (14 high-risk patients) still had more than 5% blasts in the BM. Twelve of these 15 patients were in remission after 2 to 4 weeks additional treatment. Poor responders often had a high initial WBC, age above 10 years of T- or NULL-ALL. In spite of continuation of intensive therapy all children with more than 10% blasts in the BM on day 28 suffered an early relapse except 2 who were transplanted in first remission. Event-free survival for the poor responders is 0.15 compared to 0.71 (p = 0.0001) for the good responders (median observation time 48 months). In multivariate analysis remission status on day 28 was the only significant prognostic factor in high-risk patients above one year of age; traditional risk factors as initial WBC, age above 10 years, hepatosplenomegaly, and immunological subtype were of no prognostic significance in this study. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942931 TI - [Cardiomyopathy after osteosarcoma treatment: a contribution to the cardiotoxicity of adriamycin]. AB - The frequency and severity of clinical and subclinical heart damage were studied in patients who had been treated with adriamycin (ADR) as part of the Cooperative Osteosarcoma Studies (COSS). The study charts of 785 patients from 63 participating institutions were reviewed: The overall incidence of drug-induced congestive heart failure was 2.2% (17 cases, 5 fatal). Late left ventricular function was studied in 29 tumor free survivors 81 +/- 41 month after treatment with 342 +/- 113 mg/m2 ADR. A detailed history and physical exam for signs of overt heart disease were obtained. M-mode echocardiography (ECHO, 29 cases) with evaluation of the fractional shortening rate (FS) and radionuclide ventriculography (RNV, 18 cases) with determination of the systolic ejection fraction at rest (EF) were used to screen for subclinical cardiac disease. Impaired cardiac function leading to pathological values was documented in close to one half of these patients. The frequency and severity of clinical and subclinical heart damage increased with cumulative adriamycin and time since cessation of anthracycline therapy. PMID- 1942932 TI - [Long-term study of anthracycline-induced cardiomyopathy in children and adolescents]. AB - In order to detect changes in cardiac function, electrocardiographic, echocardiographic and radiologic studies were performed in 71 patients (age 1-26 yrs) who had been treated at the University Children's Hospital Berlin because of malignant diseases according to protocols of the DAL/GPO and had received anthracyclines (doxorubicin or daunorubicin) at cumulative doses up to 480 mg/m2 (median 280 mg/m2). Clinically overt cardiomyopathy was observed in one girl and required transient administration of digoxin. In 2 patients echocardiographic changes led to a reduction of the scheduled anthracycline doses. No patient died from congestive heart failure. During treatment, an increase in the cardiothoracic index was observed in 14 children, and in 16 the ECG showed pathological findings. A decrease in contractility to 25% or less as detected by ultrasound was seen in 15 patients. More than 50% of patients developed echocardiographical signs indicating an impairment of myocardial function. However, persistent changes were only found in 1 patient after discontinuation of treatment. Long-term echocardiographic follow-up studies for 4-48 months (median 14 months) after completion of anthracycline therapy were performed in 18 patients and the findings compared to matched-pair controls. The observed M-mode parameters were completely normal, and the ejection fractions calculated from the two-dimensional ultrasound investigations were in the normal range but slightly diminished compared to controls. Cardiac ultrasound is a non-invasive, reproducible and tolerable procedure for early detection of an anthracycline cardiomyopathy. In our patients, time of occurrence and the extent of pathological changes were not associated with the cumulative applied anthracycline doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942933 TI - [Testicular function after OPA/COMP chemotherapy without procarbazine in boys with Hodgkin's disease. Results in 25 patients of the DAL-HD-85 study]. AB - Gonadal function was evaluated in 25 boys treated for Hodgkin's disease according to the DAL-HD-85 protocol with OPA- or OPA/COMP-chemotherapy (vincristine prednisone-adriamycine/cyclophosphamide-vincristine-m ethotrexate- prednisone). All boys were in first continuous complete remission for 6 to 45 months at chronological ages varying from 14.0 to 18.9 years. Testosterone, basal and GnRH stimulated LH- and FSH-levels were measured. Gonadal function was normal in 16 patients treated with 2 cycles of OPA-chemotherapy in Hodgkin stages I-IIA. 9 patients were treated with 2 OPA- and 2 or 4 COMP-cycles of chemotherapy and had received mean cyclophosphamide doses ranging from 2004 to 3722 mg/m2. Again, no major testicular damage was noted, though some patients had increased stimulated LH-levels possibly indicating compensated Leydig cell-insufficiency. Our results demonstrate, that testicular function is not severely affected when patients are treated for Hodgkin's disease without procarbazine even if cyclophosphamide is given in cumulative doses below 3800 mg/m2. The previously documented severe testicular damage in boys treated according to the DAL-studies HD-78 and HD-82 is thus a result of the gonadotoxic action of procarbazine. PMID- 1942934 TI - [Beta thalassemia: molecular pathogenesis and clinical variability]. AB - Clinically, homozygous beta-thalassaemia is characterised by a severe anaemia requiring regular transfusion therapy in most patients. However, there is a marked clinical variability ranging from this severe picture to the virtual absence of symptoms and haematological abnormalities. Biochemically, beta-globin synthesis in the erythroid precursors of the bone marrow is reduced or absent resulting in a relative excess of insoluble alpha-globin chains and dyserythropoiesis. The molecular genetics of this disorder is highly variable involving a multitude of different mutations of the beta-globin gene. These mutations can inactivate gene expression at all levels on its way from DNA to mature haemoglobin. The clinical picture is largely determined by the type of mutations inherited. Additionally the degree of alpha-globin chain excess can be influenced by the co-inheritance of alpha-thalassaemia or mutations resulting in the hereditary persistence of fetal globin synthesis (HPFH). This review discusses the relationship between the molecular defect and the clinical picture of patients with beta-thalassaemia. PMID- 1942935 TI - [Disorders of the membrane skeleton of erythrocytes in hereditary spherocytosis and elliptocytosis: significance of the molecular defect for pathogenesis and clinical severity]. AB - During recent years an increasing number of inherited variants of erythrocyte membrane proteins and defects of the membrane skeleton could be described. Mostly these defects explain the pathogenesis of hemolytic anemias due to erythrocyte membrane defects. For hereditary spherocytosis and elliptocytosis a close correlation between the clinical severity and the biochemical defect was found; thus biochemical characterization can give valuable information about the expected course of the disease and the need for splenectomy. The erythrocyte membrane skeleton stretches along the inner surface of the membrane; it provides the stability of the erythrocyte under circulatory shear stress. The membrane skeleton consists of spectrin, actin, band 4.1 and band 4.9. Spectrin is the major component. In the membrane mostly all spectrin self-associates to the tetrameric form: one tetramer is formed by two alpha and two beta-chains. By denaturing SDS polyacrylamide gelelectrophoresis the composition of the membrane proteins can be analysed. The portion of tetrameric and dimeric spectrin is determined on native agarose gel electrophoresis. The concentration of spectrin in the membrane can be measured by an enzyme linked immunosorbent assay using monoclonal antibodies against human spectrin. By polymerase chain reaction and DNA sequencing the moleculargenetic cause of singular membrane defects was clarified. Hereditary spherocytosis was mostly due to a more or less diminished concentration of spectrin. Based on hematological, clinical' and biochemical observations, a new classification of spherocytosis (mild, moderate and severe form) is proposed. In addition to routine hematologic determinations and osmotic fragility, erythrocyte spectrin content is taken into account. The disease severity correlates with the diminution of spectrin. In hereditary elliptocytosis the concentration of tetrameric spectrin is reduced in about 30% of the patients. Defects of the N-terminal alpha I 80,000 dalton peptide are predominantly found. The defective alpha chain can be further studied by analysis of "tryptic" peptides after limited tryptic digestion of the spectrin. According to the reduced molecular weight of the anomalous tryptic alpha I peptide the variant spectrin alpha chains are designed as Spectrin alpha I/46, Sp alpha I/50, Sp alpha I/65, Sp alpha I/74 and Sp alpha I/78. In most cases a single amino acid substitution of the alpha chain could be proven. Until now only singular patients with hereditary elliptocytosis due to a shortened spectrin beta chain have been described. The shortening of the beta chain is due to a loss of the C-terminal phosphorylated peptide. The molecular cause is a defect at the 3' end of the beta spectrin gen, resulting in a premature termination of the peptide chain synthesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1942936 TI - [Effect of etamsylate on hemorrhagic diathesis of children with oncologic diseases. Retrospective matched-pair analysis of 64 patients in a study of 100 patients of the Munster University Pediatric Clinic]. AB - The hemostatic efficacy of ethamsylate studied by a matched-pair analysis was not proved to be statistically significant. The appearance of bleeding signs as well as the frequency of platelet transfusions have been examined. An important side effect was found in patients receiving ethamsylate: severe leucocytopenia (less than 1000 leucocytes/microliters) was noticed more frequently followed by an enhanced susceptibility to infections. The incidence of septic infections was proved to be significantly increased in an extended sample of 100 patients. PMID- 1942937 TI - The granulocyte/macrophage-colony stimulating factor (GM-CSF): basic science and clinical application. AB - Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) stimulates the production as well as the function of myeloid cells, i.e. granulocytes and macrophages. Proliferative effects are exerted on the level of the multipotent as well as the unipotent progenitor cell. Functional effects on mature phagocytes comprise bactericidal and tumoricidal mechanisms including induction of cytokine release. GM-CSF receptors are present on normal hematopoietic progenitors as well as on mature granulocytes, on leukemic cells and some non-hematopoietic cells. Alteration of the GM-CSF gene has been associated with distinct features of AML and ALL. The glycosilated molecule is produced by various hemolymphopoietic and possibly non-hematopoietic cells, amongst whom T-lymphocytes and marrow stroma may be most relevant for myelopoiesis. The regulation of gene expression is exerted on both transcriptional and posttranscriptional levels of gene expression. GM-CSF production may play a role in steady state as well as in stress hematopoiesis. In vivo application of GM-CSF leads to a marked increase of phagocytes, in particular granulocytes. GM-CSF reduces the duration of neutropenia following aplasiogenic and ablative therapy. GM-CSF may possibly be helpful in the treatment of victims of radiation accidents and in patients with acquired neutropenias and glykogenosis IB. The curative potential for the underlying malignant disease is to be investigated in the present cooperative european Ewing's sarcoma study. PMID- 1942938 TI - [Increased expression of the MYCN oncogene in human neuroblastoma cells and possible, new therapeutic approaches]. AB - Human neuroblastomas of advanced stages often display amplification with a consecutive enhanced expression of the MYCN oncogene. Enhanced MYCN expression is thought to contribute in a causative manner to the progression of neuroblastomas, but the mechanisms by which this may occur have remained unclear. By transfecting human neuroblastoma cells that display a normal MYCN expression with the human MYCN oncogene, we have generated a cell line with enhanced MYCN expression and thereby were able to compare the biological and biochemical properties of the transfected and non-transfected cells. We have demonstrated autocrine growth factors in the MYCN-transfected, but not the non-transfected, neuroblastoma cells. Identification of the primary structures of these factors may help to develop specific antagonists in order to improve the therapy of advanced neuroblastomas. Currently, this could be done by application of genistein or tumor necrosis factor. As we could demonstrate for the first time, the dietary constituent genistein is able to inhibit the proliferation of neuroblastoma cells with enhanced and normal MYCN expression, but also that of cells derived from other solid pediatric tumors. In contrast, tumor necrosis factor is able to inhibit selectively the proliferation of neuroblastoma cells with enhanced MYCN expression. We suggest that tumor necrosis factor might improve the therapy of advanced human neuroblastomas. PMID- 1942939 TI - [N-myc status of neuroblastoma from bone marrow cells]. AB - The analysis of the N-myc gene in bone marrow specimens at the time of initial diagnosis and as well at the time of relapse from patients with Neuroblastoma stage IV and bone marrow infiltration could give some informations about the N myc status of these patients. In stage IV neuroblastoma patients with bone marrow infiltration an estimation of the N-myc gene amplification should be attempted, if otherwise no information about the tumor content of the N-myc gene could be gathered. In our investigation we could demonstrate a Southern-blot-analysis of 27 bone marrow specimens with respect to the N-myc gene status which correlated qualitatively well to the N-myc amplification detected later on in the corresponding tumor tissue. In six cases the tumor infiltrated bone marrow showed a clear amplification of the N-myc gene. Because of the contamination by non malignant cells in bone marrow there was a quantitative difference in the calculated N-myc gene copies between the examined bone marrow specimens and corresponding tumor tissue. PMID- 1942940 TI - [Clinical and neuroradiological findings in gliomatosis of the brain with special reference to magnetic resonance tomography]. AB - We present three cases of GC, one belonging to the brainstem, and two belonging to the hemisphere type. Two cases were investigated by MRI. Tumour infiltration, while yielding only vague CT findings, was well demonstrated in MR studies where extensive hyperintense lesions were found in T2- and proton density images. In patients studied by MR these were localized within the white matter and corpus callosum. No enhancement was seen after administration of Gd- DTPA. These findings may strongly indicate the presence of gliomatosis cerebri, when clinical and laboratory data exclude inflammatory or neurodegenerative disease. Despite the good delineation of white matter changes stereotactic biopsy remains necessary to confirm the diagnosis of gliomatosis cerebri pathohistologically. PMID- 1942941 TI - [Importance of germ cell mosaic for genetic counseling of families with Duchenne and Becker muscular dystrophy]. AB - Germ cell mosaics were demonstrated in Duchenne's and Becker's muscular dystrophy by molecular genetic methods. These findings affect risk estimates in these x chromosomal muscular diseases. The mutation-selection equilibrium for x chromosomally lethal inheritance for determining the a priori probability for risk estimate according to the Bayes theorem must therefore be redefined to take the germ cell mosaic problem into account. Taking Duchenne's and Becker's progressive muscular dystrophy as an example, the article explains how the estimation of the heterozygote risk in women seeking advice changes in different family situations. PMID- 1942942 TI - [Thrombolysis with rt-PA in children with arterial and venous thromboses--a new therapy concept]. AB - Thrombolytic therapy usually used for thrombosis in the adult has been administered as a therapeutic regiment in pediatric patients (parental consent was sought prior to the treatment with rt-PA). We report our experience with rt PA in 17 children and adolescents suffering from arterial (n = 4) or venous thrombosis (n = 13) due to local rhabdomyosarcoma, acute lymphoblastic leukemia, chronic myeloblastosis, sickle cell anaemia, parenteral nutrition, haemolytic uremic syndrome, central arterial and venous catheters and septicemia Thrombotic diseases have been diagnosed by Doppler ultrasound, computed tomography, angiography and phlebography. Rt-PA therapy was started immediately after diagnostic procedures had been performed. Rt-PA dose varied from 0.2 mg as a single dose to 0.8 mg/kg bw/d over a three day period in children local thrombolysis was performed. In patients requiring systemic thrombolytic therapy rt-PA was administered from 0.8 mg/kg bw/d in three days to 2.0 mg/kg bw/d over a whole period of three weeks in both groups during thrombolysis low dose heparin was added. When rt-PA infusion was terminated heparin (70 IU - 400 IU/kg bw/d) was administered for 7 to 14 days in order to prevent reocclusion. Later prophylaxis with coumarin derivatives in venous thrombosis and antiplatelet agents in arterial occlusive diseases was performed. In no patient did we see a decrease of fibrinogen and plasminogen during rt-PA therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1942943 TI - [Successful lysis of a septic thrombosis of the superior vena cava using recombinant tissue-plasminogen activator]. AB - Recombinant human tissue-type plasminogen activator (rt-PA) was successfully given via central vein to a 1.7 year old child with angiographically documented septic vena cava superior thrombosis Thrombolytic therapy with rt-PA was started with 0.2 mg/kg as a slow bolus injection followed by an infusion of 0.8 mg/kg over 60 min. rt-PA was applicated 12 hours after an urokinase bolus in a dosage of 8000 E/kg and heparin infusion of 500 E/kg/die. No clinical side effects or alterations in the plasmatic coagulation profile were noted. The prompt clinical response suggests that the use of rt-PA in thrombotic disease should be investigated further to establish efficacy, dosing guidelines, complication rates, and contraindications in childhood. PMID- 1942944 TI - [Pulmonary sequelae of long-term ventilation of very low birth weight premature infants. Results of a follow-up study of 6-to-9-year-old children]. AB - Fifty six children with a birth weight of less than 1500 g and gestational age less than 34 weeks were studied at a mean age of 7.7 years. All had required mechanical ventilation, 36 suffered from hyaline membrane disease, 17 from atelectasis and three from pneumonia. Of these patients 37 developed broncho pulmonary dysplasia (BPD). The study included skin prick test, measurement of ciliary beat frequency, chest X-ray, whole-body plethysmography and histamine challenge. Eight patients suffered from recurrent pulmonary infections up to the age of 4 years. Eleven children had a positive skin prick test. Three suffered from allergic asthma and six from hay-fever. The family history of atopy in these premature infants was no different from that of the general population. Ciliary beat frequency was normal in all cases (frequency: 11.8 +/- 1.8 Hz). In 34 patients X-rays showed minimal changes (peribronchial thickening n = 6, mild emphysema n = 28). Pulmonary function was normal except for an increase of thoracic gas volume which was correlated to grade of BPD according to Northway. There was a significant correlation between oxygen-score and radiological stage of BPD (r = 0.7). Histamine challenge showed hyperresponsiveness in 53% of the children. Eight patients showed a threshold similar of mild asthma (less than 1000 micrograms histamine per ml). The degree of airway hyperreactivity was correlated to the grade of BPD (r = 0.7; p less than 0.01) and the oxygen-score (r = -0.63; p less than 0.05). The oxygen-score may be considered a predictor of hyperresponsiveness and pulmonary outcome in later childhood. PMID- 1942945 TI - [Ultrasonography in urinary tract infection in infancy]. AB - In a prospective study 77 infants (35 boys) with a mean age of 5.23 months were studied to determine the value of sonography for detection of renal parenchymal involvement in urinary tract infection (UTI). Sonography was performed during UTI and about one month later. UTI was classified as upper and lower UTI according to the clinical and laboratory findings; radiological investigations (voiding cystoureterography = MCU) were performed in all infants. 40 infants were classified to have upper UTI. There was a high sensitivity (80%) and specificity (97%) for detection of renal involvement by sonography. Incidence for vesicoureteral reflux (VUR) was significantly higher in infants with repeated pathological findings on sonography. In contrast, no VUR was detected on MCU in all 12 infants with normal findings in both sonographic examinations. Yet, sonography without catheterization could not detect VUR in all infants with radiologically confirmed reflux. Our results show, that sonography is of definite value in infants with UTI, but cannot replace radiological work up. PMID- 1942946 TI - [The value of C-reative protein analysis for the differential diagnosis of non acute appendicitis]. AB - Appendicitis is one of the most common causes for laparatomy in children. Diagnosis can be very problematic, especially if appendicitis is combined with gastro-enteritis. Furthermore, difficulties can be encountered in diagnosis of diseases such as mucoviscidosis, leukosis, immunosuppressive or chemotherapy are present. In addition to the common clinical examination we have to look for other methods to complete the indication for appendectomy. Therefore in 1985 we added the CRP-determination to our diagnostics for patients with suspected appendicitis. In a retrospective study 269 patients who had signs of acute appendicitis were examined. We found that the determination of the CRP-level, in conjunction with the standard parameters of appendicitis, represents a valuable addition to the diagnostic armamentarium. However our data shows, that the CRP level in itself cannot be regarded as a sole criteria for an unambiguous diagnosis of non-acute appendicitis, as it is the case with any other appendicitis parameter. PMID- 1942947 TI - [Autosomal dominant polycystic kidney disease in infancy]. AB - We report on a 6 months old infant with suddenly developed severe arterial hypertension caused by polycystic kidneys. Examinations of the relatives revealed similar changes of the kidneys in 4 adults and 5 children. They were all diagnosed to have autosomal dominant polycystic kidney disease. Excretory kidney function of all patients is normal; however, blood pressure was raised in the adults. We would like to stress the importance of family screening in this disease, in particular with regard to possible early diagnosis and treatment of arterial hypertension. The long-term prognosis of the early manifestation of the dominantly inherited cystic kidney disease is uncertain. PMID- 1942948 TI - [The 1-hour oxycardiorespirography as routine study in the diagnosis of cardiorespiratory dysregulation in infancy--an attempt at establishing normal values]. AB - Because of the growing demand to evaluate cardiorespiratory dysfunctions the short-time oxycardiorespirography becomes a more and more important and powerful tool in the daily clinical routine. Therefore, from about one hour lasting records we studied the distribution of MA-values (mean apnea duration), duration of the longest apnea, percentage of periodic breathing time, lowest heart rate values, lowest transcutaneous PO2 values and highest transcutaneous PCO2 values in an obstetrical optimal low-risk group of 90 infants and a obstetrical non optimal group of 152 infants between four and ten weeks of age. Percentiles of each variable were calculated, and we suggest the 90th percentiles as new threshold values to judge these short-time recordings. In comparison to relevant data from the literature we could demonstrate that deviating threshold values have to be applied to short-time recordings in comparison to long-time recordings. In addition, the respiratory behaviour of the optimal group is compared to that of the non-optimal group of the same age. Interestingly enough, no difference in the respiratory behaviour between these groups could be demonstrated. PMID- 1942949 TI - [Creatine-kinase MM in the perinatal period]. AB - One hundred eight newborns (gestational age 36 + 1.8 weeks and birth weight 2860 +/- 240 g) had muscle type Creatine-Kinase activity (CK-MM) assayed immediately after birth (CK-I) and serially at 6-10 h (CK-II), 20-30 h (CK-III) and 40-60 h (CK-IV) of age. Using statistical Regression analysis, CK-MM levels were correlated to four perinatal parameters: gestational age, birth weight, neonatal acidosis (pH less than 7.15), mode of delivery (vaginal/cesarean section). It was observed that CK-MM activity was dependent on gestational age and correlated to the mode of delivery at time III (600 U/l) and IV (400 U/l) comparing the mean serum values of 156 + 44 U/l observed in atraumatic delivery (p less than or equal to 0.05). Our results demonstrate markedly higher levels of CK-MM following vaginal delivery especially if complicated by forceps, vacuum and breech presentation, suggesting that birth trauma may be responsible for this phenomenon. PMID- 1942950 TI - [Tuberculosis and cystic fibrosis]. AB - Mycobacterial infections are rarely reported in Cystic Fibrosis patients although they quite often develop predisposing risk factors such as underweight, secondary diabetes mellitus and chronic inflammatory pulmonary disease. Furthermore glucocorticoid therapy is mandatory in some patients. CF heterozygotes are said to have a selective advantage due to an increased host resistance against Mycobacterium tuberculosis. In this survey 1926 CF patients were investigated for the incidence of tuberculin conversion and manifest infection with mycobacterium tuberculosis in the Federal Republic of Germany (FRG). The results do not support the hypothesis of increased host resistance nor do they show any evidence of a higher risk for tuberculosis in CF. Implications for prophylactic, diagnostic and therapeutic measures are discussed in accordance to the recent epidemiologic data of tuberculosis in the FRG. PMID- 1942951 TI - [Serum potassium level in healthy neonates and infants with asphyxia in the first 144 hours of life]. AB - Postpartal increase in the plasma potassium concentration of asphyxiated newborn infants is a very rare complication with possibly deleterious outcome. In a group of 98 asphyxiated and 87 healthy infants we have not seen either a case of severe hyperkalemia or rhythm disturbances. We found lower reference-ranges for plasma potassium concentration in the group of healthy infants than previously published, which we would like to introduce. The pathogenesis of hyperkalemia in hypoxia is not yet fully understood. Further experimental investigations will be necessary. PMID- 1942952 TI - [Case report of a nutrition-induced anemia due to folic acid deficiency]. AB - Because of anaemia and dystrophy a girl was admitted to hospital. By bone marrow aspiration the diagnosis of a megalocytic anaemia was established. The determination of folic acid revealed a severe folate deficiency caused by education problems with consecutive malnutrition. Under folic acid replacement therapy and intensive talks with the parents the girl recovered from her illness and after change of nutrition she developed well without any further folic acid replacement. PMID- 1942954 TI - Hyperlipidemia in acute hemolysis. AB - In 27 (78%) of 36 patients with massive hemolysis (defined as a fall in hematocrit of more than 12% within 12 h due to intravascular red cell destruction), hypertriglyceridemia (plasma triglycerides greater than 175 mg/dl) was present or appeared within two days after the hemolytic crisis. Eighteen subjects with triglycerides exceeding 300 mg/dl (peak 516 +/- 39 mg/dl) were further analyzed. The development of hyperlipidemia was independent of the etiology of hemolysis (microangiopathic hemolytic disease 7, toxicemia 3, parainfectious complications 3, autoimmune hemolysis 2, glucose-6-phosphate dehydrogenase deficiency 2). Factors known to increase plasma triglycerides, such as shock, infections, or pancreatitis, were present in only a few cases. Hemolysis-associated complications were activation of intravascular coagulation (16), coma (13), acute renal failure (13), and respiratory insufficiency (5), organ dysfunctions indicating diffuse microvascular injury. Plasma triglycerides fell within a few days if the cause of red cell destruction was eliminated. In 5 of the 8 patients presenting with triglycerides below 175 mg/dl, severe hepatic dysfunction was present. We conclude that hemolysis causes transient hyperlipidemia, either directly by red cell destruction or indirectly by inducing intravascular coagulation, and possibly due to both increased triglyceride synthesis and decreased catabolism. PMID- 1942953 TI - [Alloimmunization and transfusion refractoriness to thrombocyte substitution]. AB - No generally accepted policy for avoiding HLA-alloimmunization has so far been established. However, several studies suggest that single-donor instead of random donor transfusions, white cell depletion, UV-radiation of blood products or application of cyclosporine to the recipient may avoid or at least delay alloimmunization. With regard to cost effectiveness, it would be essential to identify patients with the highest risk of developing alloimmunization. For the time being, transfusion of crossmatch-compatible HLA-selected single donor platelets should be restricted to alloimmunized patients, refractory to pooled random donor platelets. PMID- 1942955 TI - Excessive hypernatremia in a patient with renal amyloid disease. AB - A 24-year-old Italian male presented with a nephrotic syndrome in September 1984. In February 1985 renal biopsy showed amyloid disease with tubular atrophy and interstitial fibrosis. Edema was treated with furosemide, and cholchicine was started. Because he feared side effects of drug therapy, the patient stopped all medication by July 1985. Instead, he decided to restrict severely fluids in order to fight edema. In early November 1985 his family noted he was becoming increasingly lethargic. Two weeks later, on his admission to the hospital, he had a serum sodium concentration of 193 mmol/l and serum osmolality of 397 mosm/kg. Apart from mild mental status changes neurological examination was normal. The fluid deficit was slowly corrected. He was discharged three weeks later with normal serum electrolytes. This case demonstrates that (1) severe hypernatremia can present with mild neurological symptoms and (2) it can be survived provided that it develops slowly and is corrected cautiously. PMID- 1942956 TI - Intracranial germ cell tumor mimicking anorexia nervosa. AB - A previously healthy seventeen-year-old boy developed loss of weight, poor appetite, and aversion to food. Physical examination being normal, anorexia nervosa was suspected. Thirteen months later a CT scan revealed a mass in the third ventricle histologically proven to be a malignant teratoma. To our knowledge anorexia nervosa is only extremely rarely the presenting feature of intracranial germ cell tumors. PMID- 1942958 TI - Upper lobe relapse of Pneumocystis carinii pneumonia during aerosolized pentamidine prophylaxis. AB - A patient with a history of Pneumocystis carinii pneumonia (PCP) inhaled aerosolized pentamidine (AP) for secondary prophylaxis of PCP. Nine months after the first PCP episode he presented with pulmonary upper-lobe infiltrations demonstrated by chest x-ray, and bronchoalveolar lavage confirmed the diagnosis of PCP. The clinical course and possible explanations for this unusual form of PCP are presented. The case emphasizes the importance of clinical controls for early diagnosis of relapse of PCP in patients inhaling aerosolized pentamidine. Monitoring of serum lactate dehydrogenase levels appeared to be important in the follow-up of the patient described. PMID- 1942957 TI - Intestinal microsporidiosis in a German patient with AIDS. AB - Since intestinal microsporidiosis might be of importance in the pathogenesis of gastrointestinal symptoms in patients infected with HIV, we examined duodenal biopsies of HIV-infected patients by electron microscopy. Enterocytozoon bieneusi infection of the small intestine was found in one of 23 patients studied, which gives a 95% confidence interval for the prevalence rate between 0.1% and 22%. The infected patient was a 24-year-old homosexual male with AIDS who underwent upper endoscopy because of acute epigastric pain, nausea, and vomiting. These symptoms were obviously due to mesenterial Kaposi's sarcoma obstructing the duodenal passage, as was later revealed at autopsy. However, microsporidiosis might have caused the patient's eight-month history of diarrhea and weight loss, since infected cells showed signs of degeneration, and no other pathogens were ever detected in stool or biopsy. Our finding of Enterocytozoon bieneusi infection in a German AIDS patient supports the concept of a worldwide distribution of this parasite; further studies are needed to define its exact prevalence in HIV infected patients and its pathogenic relevance. PMID- 1942959 TI - [Internal biliary fistula]. PMID- 1942960 TI - [Torsion of the omental process associated with massive hemorrhage in colonic diverticulosis]. PMID- 1942961 TI - [Epilepsy and its treatment]. PMID- 1942962 TI - [Syncope in internist's practice]. PMID- 1942963 TI - [The role of subconscious thinking in the activities of scientists and physicians]. PMID- 1942964 TI - [Letter to the Editor concerning the article by A.A. Frankfurt "Various methodological aspects of patients' questioning" ("Klinicheskaia meditsina", No. 6, 1990)] [letter]. PMID- 1942965 TI - [Arthritis]. PMID- 1942966 TI - [Trophic and regulatory relations between intestinal microflora and the macro organism (on the pathogenesis of irritable bowel syndrome)]. PMID- 1942967 TI - [The accessory gallbladder]. PMID- 1942968 TI - [Transplantation of the lungs]. AB - The paper is concerned with current status of lung transplantation. The problem was studied by the author in his own experiments, in clinics of Canada and USA. Literature data are reviewed. Special attention is focused on indications for the transplantation, taking and preservation of the transplant, prevention of the rejection, difficulties of clinical introduction of lung transplantation in this country. PMID- 1942969 TI - [Effect of nifedipine on the secretory and motor functions of the stomach and microcirculation in the gastric and duodenal walls]. PMID- 1942970 TI - [Characteristics of blood flow in the gastric mucosa in relation to its structure and function in patients with peptic ulcer]. AB - Hydrogen clearance was used to assess blood flow in fundal and antral gastric mucosa as well as in the lobule of the auricle in 127 patients with ulcer (99 duodenal and 28 gastric ulcer cases), 34 patients with gastric, duodenal, pancreatic and biliary ++non-ulcer lesions against 20 healthy subjects. The findings underwent analysis in relation to the disease form and phase, baseline characteristics of the mucosa (morphological, functional and bacteriological) and changes in them in response to pentagastrin (6 micrograms/kg), alupent (0.0075 mg/kg), clofelin (0.0015 mg/kg) administration. For ulcer involving the body of the stomach and sutured perforated duodenal ulcer, fundal and antral mucosa blood flow showed a decrease by 1/3, the lowest values presenting in the active disease phase. Diminution in gastric mucosa blood flow correlated with gravity of its gastritic lesion and was not directly related to its Campylobacter contamination. Pentagastrin stimulated blood flow in fundic mucosa and led to its 30% increase whereas the flow intensity remained unaffected in the antral mucosa and skin (lobule of the auricle). Acid production in response to pentagastrin introduction rose 3.5-fold, pepsin 2.1-fold. Alupent and clofelin do not affect blood flow causing a 30-50% increase and decrease in acid and pepsin production, respectively. Separate neurohumoral regulation of gastric mucosa blood flow and secretory activity of the latter permits differential correction of each of the impaired functions. PMID- 1942971 TI - [Degree of lipid peroxidation and vitamin E level during the treatment of peptic ulcer]. AB - The study of 468 ulcer patients treated by laser irradiation plus choline blocking agents with adjuvant alpha-tocopherol antioxidants (alpha-tocopherol acetate, wild rose and sea-buckthorn oils) provided evidence in favour of the antioxidants addition. Combination of hyperbaric oxygenation (5-6 sessions) or riboxin with choline blocking agents made antioxidants unnecessary. Biochemical findings (vitamin E and malonic dialdehyde concentrations), electron microscopic, ++histo-enzyme and amino acids studies supported the clinical evidence. PMID- 1942972 TI - [Stimulation of the motor function of the duodenum by sound waves in chronic duodenal obstruction]. AB - The study was made of sound waves effect on duodenal motility (DM) in 60 chronic sufferers with duodenal functional ileus. The exposure to 2.0-3.0 kHz sound waves of 0.57-0.73 W/cm2 intensity promoted intestinal contractions, duodenal passage of barium, enhanced biopotential, amplitude and tone. These parameters tended to acquire values similar to duodenal motility in health. PMID- 1942973 TI - [Low-intensity laser irradiation in the treatment of peptic ulcer]. AB - The course of gastric and duodenal ulcer was investigated in 120 ulcer patients exposed to low-intensity laser irradiation with 0.63 microns wave length. Compared to conventional treatment, laser therapy of ulcer has a number of advantages allowing its wide introduction in both hospital and outpatient settings. Benefits and drawbacks of endoscopic and transcutaneous laser therapy are comparatively assessed. PMID- 1942974 TI - [Low-intensity laser treatment of patients with duodenal ulcer and erosive lesions of gastric and duodenal mucosa]. AB - Ninety-eight patients were exposed to low-energy laser irradiation. Of these 52 and 31 had duodenal ulcer in aggravation phase with mucosal erosion and without it, respectively, 15 patients developed isolated erosive lesions of gastroduodenal mucosa. The energy was delivered to the target cites optically using fiber optics endoscope. Microcirculation was studied by bulbar biomicroscopy. Therapeutic response in the laser utilization proved positive being the highest for patients with a short disease history, moderate signs, small-size lesions. Normal microcirculation was not achieved though there was a trend to its improvement. PMID- 1942975 TI - [Antacid and anti-peptic effects of food in duodenal ulcer]. PMID- 1942976 TI - [Treatment of duodenal ulcer associated with chronic gastric erosions]. AB - Three groups of patients received chemotherapy for duodenal ulcer and associated chronic gastric erosion. Group I was treated by the drugs combination (methacin, almagel, gastrofarm, solcoseryl, tazepam, rudotel), group II received gastrocepin, group III venter. The results of duodenal ulcer healing were similar in all the groups, yet epigastric and/or pyloroduodenal pain was relieved more rapidly in groups II and III. The latter groups were also characterized by accelerated disappearance of fibrinous patches on the surface of the erosion. PMID- 1942977 TI - [New possibilities of prevention of acute gastric and intestinal ulcers in peritonitis with drugs of anti-hypoxic and antioxidant action]. AB - A retrospective analysis has been made of 96 cases of acute erosions and peptic ulcer emerging in diffuse purulent peritonitis. The examination and treatment of 124 patients suggested that toxic peritonitis runs with excessive accumulation of lipid peroxidation products in the serum. Administration of antihypoxic drugs and antioxidants promoted stabilization of peroxidation thus preventing gastroduodenal erosions and ulcer. PMID- 1942979 TI - [Changes in secretory immunoglobulin A level in the blood serum of patients with peptic ulcer]. AB - Serum levels of secretory IgA were measured in 66 patients with aggravation of peptic ulcer versus 52 healthy subjects. IgA concentrations in the patients were found elevated, the rise being dependent on the ulcer site, standing and severity of course. Treatment-induced decline of the ulcer exacerbation was accompanied by a fall in IgA levels. It is hold that serum IgA can serve a marker of gastroduodenal ulcer exacerbation. PMID- 1942978 TI - [Functional effects of pentagastrin and diagnostic possibilities of the pentagastrin test]. AB - The effect on gastric secretion of a single pentagastrin dose (6 micrograms/kg) against submaximal doses of histamine, euphylline and limontar was studied in 100 healthy subjects aged 20-30. It is shown that pentagastrin test corresponds to maximal histamine test allowing rough measurement of lining cells mass. Normal secretory values and mass of the lining cells have been established as well as normal secretory response of the stomach to submaximal histamine (0.008 mg/kg) and euphylline (7 mg/kg) tests. Diagnostic significance of the pentagastrin test in peptic ulcer and chronic gastritis with secretory insufficiency has been supported. There were some cases of secretory response to euphylline and limontar in pentagastrin-refractory forms of gastric secretion due to mobilization of functional cellular component of the gastric glands. Pentagastrin inhibited initially enhanced gastric evacuation though motor function of the stomach showed no response. PMID- 1942980 TI - [Status of cellular immunity in patients with peptic ulcer and different degree of acidity of gastric juice]. PMID- 1942981 TI - [Status of humoral and cellular immunity in patients with a frequently recurring form of stomach ulcer in the presence of Campylobacter pylori]. AB - The findings at examination of 42 patients with gastric ulcer exhibiting frequent relapses were comparatively assessed in relation to humoral and cellular immunity, presence of mucous microflora and Campylobacter pyloridis at the ulcer site. It is shown that in the presence of Campylobacter pyloridis specific differences in the immune response were not recorded. The same results were true for mucous microflora. PMID- 1942982 TI - [Status of the glutathione system in gastroduodenal ulcers]. AB - Clinical and experimental studies demonstrated lowering of reduced glutathione, activation of glutathione reductase and peroxidase in peptic ulcer more pronounced in associated chronic hepatitis or non-ulcerative colitis. Clinical manifestations of the disease and biochemical shifts in glutathione system go in parallel. Disturbances of glutathione system seem to be involved in the origin and recurrences of gastroduodenal ulcer. New approaches are needed in therapeutic decisions and means in peptic ulcer especially in its combination with chronic hepatitis and non-ulcerative colitis. PMID- 1942983 TI - [Pepsin activity of the stomach as a pathogenetic factor of duodenal ulcer and prognostic indicator of its course]. AB - Proteolytic activity in the stomach can play an active role in pathogenesis of duodenal ulcer (DU). When high, this activity attends a severe course of the disease. It is feasible to prognosticate DU progress in remission patients basing on gastric pepsin levels. Normal gastric pepsin levels suggest a favorable long term outcome. In DU aggravation investigations of acid-peptic aggression should be supplemented by examination of the mucous protective barrier. PMID- 1942984 TI - [The role of hyperlipoperoxidation in the development of chronic acalculous and calculous cholecystitis]. AB - Upon studying the factors contributory to development of acalculous and calculous cholecystitis it was found that bioelement composition and physicochemical properties of the bile undergo marked changes. These become more pronounced in hyperproduction of secondarylipid peroxides. Being responsible for conformation changes of biliary macromolecular structures and for cytolysis of cellular elements, hyperlipoperoxidation can determine the signs of their antigenic specificity as well as the onset of hypercholesterol- andhigh bile level of bilirubin as confirmed in guinea pig experiments. Hyperlipoperoxidation proved a powerful colloid-destabilizing factor of the bile able to trigger lithogenesis. PMID- 1942985 TI - [Clinico-biochemical evaluation of the effectiveness of plasmapheresis in the treatment of severe forms of viral hepatitis]. AB - The study was performed of clinico-biochemical effect of plasmapheresis (PA) in severe viral hepatitis B, mixed hepatitis and hepatitis delta. Altogether 24 patients, all of them HBsAg carriers, were examined. With associated acute hepatic encephalopathy, clinical effect in hepatitis of PA was insignificant notwithstanding positive biochemical changes. In the absence of hepatic encephalopathy PA effect was pronounced both clinically and biochemically. PMID- 1942986 TI - [Bacterial complications in acute hepatic failure in patients with hepatitis B]. AB - With virus hepatitis B (VHB) associated with acute hepatic insufficiency, precoma and coma, one third of the patients develop bacterial purulent inflammatory complications involving mainly biliary system and intestine. Attendant bacterial complications promoted rapid progression of hepatic coma seen commonly on day 1 10 of the disease. The diagnosis in relevant patients recognizing bacterial complications clinically should be based on alterations in the liver size, the presence of fever, elevated body temperature, relatively low decrease of prothrombin index and fibrinogen against leukocytosis with stab neutrophil shift. These symptoms call for introduction of antibacterial drugs. PMID- 1942987 TI - [Thromboxane, prostacyclin and platelet factor 4 in patients with atrial fibrillation]. AB - Thromboxane++ (TX), prostacyclin (PC) and platelet factor IV (PF) were assayed using radioimmune kits in 46 patients with cardiac fibrillation secondary to coronary heart disease and rheumatic fever. The study established elevated TX beta 2 levels, low concentrations of 6-ketoPGF1 alpha, enhanced activity of PF. Restoration of the sinus rhythm by electroimpulse treatment (EIT) brought about augmentation of the Tx-Pc-PF unbalance on day 2-3. This may give rise to "normalization" thromboembolism. On days 5-7 after EIT the intensity of platelet aggregation and PF secretion diminish. It is concluded that patients with sudden cardiac fibrillation in need of sinus rhythm correction will benefit from disaggregation and anti-coagulant therapy. PMID- 1942988 TI - [Treatment of patients with transient disorders of cerebral circulation in occlusive diseases of major blood vessels of the head using vasoactive and cardiotonic drugs]. AB - Transient circulatory disorders of the brain arising in response to stenosis and occlusion of the major head arteries in 111 patients were treated with cardiotonic and vasoactive drugs (corglycon, strophanthin, sulfocamphocain, euphylline++, cavinton, finoptin). The treatment was controlled by monitoring systemic and cerebral hemodynamic parameters. An appreciable clinical response was achieved in more patients (by 16.3%) than it was usually the case in thus untreated patients. PMID- 1942989 TI - [Chronic infections and osteochondrosis of the spine]. AB - Out of 144 patients suffering from cervical osteochondrosis, single or multiple foci of chronic infection (ENT infection, bronchitis, pneumonia, cholecystitis, pyelonephritis, ect.) were found in 99. All of them had various combinations of symptoms indicating lesions of the radices spinales, cervical spine, insufficient circulation in the vertebrobasilar area. Literature and first-hand experience suggest a conclusion on the underlying infection and allergic processes in development of the disk ossification. Relevant treatment modalities are recommended. PMID- 1942990 TI - [Effectiveness of bemitil in recurrent erysipelas]. AB - The trial entered 66 patients with recurrent erysipelas treated conventionally with addition of either immunostimulator bemitil (0.25-0.5 g/day orally for 5-7 days) or placebo. The bemitil group was free of intoxication symptoms and local manifestations, discharged from hospital sooner than the controls. Therapeutic efficacy of bemitil is due to its promotion of mononuclear phagocytes function which acts as an essential mechanism of antibacterial defence activation in patients with recurrent erysipelas. PMID- 1942991 TI - [Surgical problems of AIDS (review of foreign literature)]. PMID- 1942992 TI - [Incidence of pulmonary lesions and the role of pulmonary pathology in mortality among cancer patients]. AB - The majority of cancer patients (95%) whatever the malignancy location are shown to develop various pathological process in the lungs. 20% of lethal outcomes occur due to acute and protracted croup and focal pneumonias. Such pneumonias are often found after the patients death because of a symptomless and atypical course. These findings dictate a necessity of comprehensive pulmonological studies in cancer patients and administration of detoxication therapy to manage the bronchial obstruction syndrome registered in 39% of cancer patients probably as an early stage of further pulmonary impairment. PMID- 1942993 TI - [The role of combined use of alpha-tocopherol, vitamin C and sodium nucleinate in normalization of the peroxidation processes and antioxidant activity of blood in acute pneumonia]. PMID- 1942994 TI - [Psychosomatic correlations in patients with chronic nonspecific lung diseases associated with the obstructive syndrome]. AB - Correlations were investigated between psychic characteristics, bronchoscopic and external respiration findings in 44 chronic sufferers with nonspecific pulmonary diseases (29 with bronchial asthma, 15 with obstructive bronchitis). Bronchial permeability was assessed by bronchial constriction at breathing out. This parameter was found to vary significantly among patient groups different by anxiety status which seemed to relate to endobronchitis activity. Development of ++broncho-obstructive syndrome is thought to be due to both somatic and psychic factors. PMID- 1942995 TI - [Trans-endoscopic therapy of ulcer of the duodenal bulb with the frequently recurring course]. PMID- 1942996 TI - [Rare causes of extra-gastric deformity of the stomach]. PMID- 1942997 TI - Xanthogranulomatous pyelonephritis, perinephric type--a case report. AB - A 46 year-old woman with perinephric type of xanthogranulomatous pyelonephritis is described. She had a fever and pain with a palpable mass in her right flank. The blood analysis revealed anemia, leucocytosis, gamma-globulinemia, but no hyperlipidemia. The urine analysis showed nothing abnormal, but enterobacter was present in the urine. An intravenous pyelogram demonstrated a right non functioning kidney. The diagnosis of a perinephric abscess was made from the x ray and ultrasonogram, and a right nephrectomy was performed. The resected kidney had a tumor-like lump covered with Gerota's fascia at the postero-lateral side of the kidney. The cut surface of the kidney revealed an area of hemorrhage, blood clotting, abscess and a brownish yellow area in the perinephric fat tissue. The calyx and pelvis were normal. Histologically, the brownish yellow area was a granuloma with foam cell infiltration. The foam cells contained lipids. The renal parenchyma showed a non-specific chronic pyelonephritis. PMID- 1942998 TI - An 82 year-old patient with sarcoidosis. AB - An 82 year-old woman presented with bilateral uveitis suggestive of ocular sarcoidosis, which led to a clouded vision. She was diagnosed as having sarcoidosis because of an elevated level of serum angiotensin converting enzyme (ACE), findings from a Ga67 scintiscan and the bilateral uveitis, although her chest X-ray film was normal. This patient is one of the most oldest patients on record to have sarcoidosis. PMID- 1942999 TI - Complete sacral agenesis--a case report. AB - We report a case of a girl with complete sacral agenesis associated with arthrogrypotic-like deformity. This case demonstrates that a posterior knee release and braces following operation are effective treatment for knee-flexion contractures. Accordingly it is suggested that a supracondylar osteotomy is not required for mild or moderate recurrence of knee-flexion contractures. PMID- 1943000 TI - Association between nocturnal penile tumescence (NPT) and sleep of stage 1 with REMs in chronic alcoholics. AB - An unusual sleep stage, composed of low amplitude theta activity in the EEG, rapid eye movements (REMs) and tonic EMG in skeletal muscles has been found in chronic alcoholics. Some researchers regard this as a variation of REM sleep, but others believe it to be fundamentally different from REM sleep. Since it is well known that penile tumescence (PT) occurs during REM sleep, I investigated the occurrence of PT during this unusual sleep stage in male alcoholics to determine whether it should be viewed as REM sleep. PT did not occur during this stage. NO differences were found in the amount of REM sleep between chronic alcoholics and normal controls. Moreover, the mean duration of total PT, and the mean durations of maximum and semi-episode PT were shorter in the alcoholics than in normal controls. PMID- 1943001 TI - Spontaneous portacaval shunts in patients with gastric cancer and hepatic cirrhosis. AB - Two rare cases of a spontaneous portacaval shunt occurring in patients with gastric cancer and hepatic cirrhosis are retrospectively reviewed with special attention for the operative indications and techniques. One patient underwent proximal gastrectomy for a IIa cancer in the C region with splenectomy and closure of the splenorenal shunt, and died two years and 3 months later due to hepatic failure. The other patient underwent distal gastrectomy for IIa + IIc, IIc double cancers in the M and A regions with splenectomy through an upper transverse abdominal incision that ligated and divided the paraumbilico-caval shunt, and is alive and well 1 year and 2 months, postoperatively. The ICG-R15 was markedly decreased and the K-ICG and ICG-Rmax were improved following the operation in both cases. The preoperative chronic encephalopathy and hyperammonemia disappeared postoperatively in both cases. PMID- 1943002 TI - Torsion of parovarian cyst--report of two cases. AB - A parovarian cyst oxiginates from the tissue of the broad ligament, predominantly from mesothelium covering the peritoneum but also from paramesonephric and mesonephric remnants. Clinically, torsion of a parovarian cyst is uncommon, and it is difficult to distinguish it from torsion of other adnexal masses, an ovarian accident, appendicitis, etc. Recently, we experienced two cases of torsion of parovarian cysts. In one case, it was associated with 32 weeks' intrauterine gestation. In this case, pelvic sonography during the first and second trimester showed no cystic lesions. In the other case, a lower abdominal pain continued about two weeks. A sonogram revealed a very small cyst like a follicle. These twisted parovarian cysts were removed at laparotomy. The clinical and pathological features of the torsion of parovarian cysts are briefly discussed and the literature is reviewed. PMID- 1943003 TI - The effect of bile juice reflux on the development of remnant stomach carcinoma. AB - Experimental studies have revealed that duodenogastric reflux subsequent to gastrectomy was one of the most significant factors for the development of carcinoma in the remnant stomach. For this reason, the binding of carcinogenic agents to the nucleic acids in the gastric mucosa exposed to the duodenal contents were studied using an organ culture method. The intracellular DNA levels bound with carcinogenic agents were significantly increased in the mucosa of the remnant stomach, as compared to the parietal mucosa in the whole stomach. The remnant stomach may therefore provide an environment that enhances the development of cancer. PMID- 1943004 TI - [The Thuringia secretary for health on nursing]. PMID- 1943005 TI - [Blueprint for unified legislation for continuing education in psychiatric nursing with rules for further education and examinations]. PMID- 1943006 TI - [The family group. In the field of tension between the families' expectations and the aims of the therapists]. PMID- 1943007 TI - [Treatment of chronically substance dependent patients]. PMID- 1943009 TI - [Study: does the nursing personnel want wages according to efficiency? Psychiatric personnel in the forefront]. PMID- 1943008 TI - [Continued salary payments in cases of sickness and education furlough]. PMID- 1943010 TI - [Considerations on odors in cancer patients in their terminal phase. "I can smell you"]. PMID- 1943011 TI - [Organ donation and transplantation]. PMID- 1943012 TI - [Towards recognized nursing practice]. PMID- 1943013 TI - [Personnel shortage. Understanding the dynamics]. PMID- 1943014 TI - [For people with permanent health handicaps--appropriate support]. PMID- 1943015 TI - [Time to act]. PMID- 1943021 TI - [Do children have to stay inside because of the summer smog?]. PMID- 1943017 TI - [What kind of power do the caregivers have--and how do they use it. Power as a relationship]. PMID- 1943016 TI - [Facets of today's psychiatry. The powerlessness of the psychiatric patient--and his nurse. Interview by Ria Frick]. PMID- 1943020 TI - [Ozone pollution in Switzerland .... still no change in sight]. PMID- 1943018 TI - [Meeting "Overstressed hospitals, overstressed nurses". Relief is possible]. PMID- 1943019 TI - [Considerations on the double role of the anesthesia personnel. Anesthesia versus nursing?]. PMID- 1943022 TI - [Admitting psycho-geriatric patients. Towards a new concept of care]. PMID- 1943023 TI - AIDS testing: science vs. hysteria. PMID- 1943024 TI - Upper gastrointestinal transit in humans. PMID- 1943025 TI - Sinusitis and headache. AB - Nasal endoscopic examination and CT views of the sinuses were obtained in patients with symptoms of headache and sinusitis who had failed to respond to conservative medical therapy. Endoscopic sinus surgery has challenged traditional concepts of sinus disease management. The site of obstruction rather than the extent of the disease is the major concern. Removal of pressure points with reestablishment of a competent airway, and revision of sinus passageways to facilitate mucociliary drainage and ventilation of the obstructed cavity can benefit patients with chronic headaches. PMID- 1943026 TI - Traumatic diaphragmatic disruption: a five-year experience at Spartanburg Regional Medical Center. AB - Diagnosing diaphragmatic disruption requires a high level of suspicion. Diaphragmatic disruption must be considered in all cases of severe thoracoabdominal trauma. Initial chest x-rays can provide much useful information. Pathognomonic signs of diaphragmatic disruption on chest x-ray are stomach gas bubble in the chest, contrast material in the chest after its introduction into the upper gastrointestinal tract, and a nasogastric tube positioned above the diaphragm. In some cases a diaphragmatic disruption may not be diagnosed until exploratory laparotomy is done for associated injuries. One must carefully inspect both hemidiaphragms at the time of surgery, especially in injuries associated with penetrating trauma. Repair of the disruption should be undertaken at the time of diagnosis. The repair should be approached through a midline abdominal incision. A chest incision should be considered in cases of right-sided diaphragmatic disruption, or to assist with the delivery of contents back into the abdomen. Non-absorbable suture is recommended for all repairs of diaphragmatic disruption. PMID- 1943027 TI - Breast implants. PMID- 1943028 TI - Venous thromboembolism: anticoagulation, lysis, or filter? AB - Experience and review of the literature suggest that when deep venous thrombosis does occur, standard anticoagulation with heparin followed by Coumadin is the mainstay of treatment for both deep venous thrombosis and pulmonary emboli. However, thrombolytic therapy with urokinase or streptokinase may benefit selected patients. Percutaneous caval interruption is the optimal technique to prevent pulmonary embolization, but should be reserved for patients who have contraindications to anticoagulation therapy or recurrent emboli despite adequate anticoagulation. Selected high risk patients may also be candidates for caval interruption. PMID- 1943029 TI - Lyme disease in South Carolina. AB - Lyme disease is present in South Carolina, though not as prevalent as in many other states in the country. The characteristics of South Carolina cases are similar to those of the nation as a whole. The tick vector of Lyme disease in the Southeast is not clearly established, but is thought to be Ixodes scapularis. Questions remain concerning the prevalence of infection in local ticks with Borrelia burgdorferi, and the risk to a person bitten by a tick in South Carolina. PMID- 1943030 TI - 1990 South Carolina Physician Survey of tick, spider and fire ant morbidity. AB - A population of 2,366 primary care physicians in South Carolina was surveyed by mail to estimate the number of cases of insect morbidity treated in 1990. A response rate of 42.3 percent was obtained. Cases reported totaled 414 for Rocky Mountain spotted fever, 334 for Lyme disease, 143 black widow and 478 brown recluse spider bites and 4,975 fire ant stings. These are counts of cases from a mail survey, not from a research-based study. Five deaths were also reported; two for Rocky Mountain spotted fever, two due to black widow spider bites and one fire ant anaphylaxis. PMID- 1943031 TI - Non-Lyme disease. AB - Four syndromes of non-Lyme disease are described on the basis of the history and serologic test result. Recognition of non-Lyme disease enables the physician to avoid unnecessary treatment and to keep considering the possibility of alternative diagnoses. PMID- 1943032 TI - Lyme disease: how common in South Carolina? PMID- 1943034 TI - Reactive or pro-active medicine. PMID- 1943033 TI - Misleading and false information regarding implants for breast contouring and breast reconstruction. PMID- 1943035 TI - Current status of urologic cancer and its management in South Carolina. PMID- 1943036 TI - Immediate breast reconstruction. PMID- 1943037 TI - South Carolina obstetricians' initiation and expectations of genetic counseling referral. PMID- 1943038 TI - Round three: HIV and public policy versus healthcare workers and patients. PMID- 1943039 TI - Do not resuscitate? PMID- 1943040 TI - Dietary and physical activity assessment in school-aged children: measurement issues. PMID- 1943041 TI - Taking a bite out of eating behavior: food records and food recalls of children. PMID- 1943042 TI - Measuring food use in school-aged children. PMID- 1943043 TI - Observation in assessment of children's dietary practices. PMID- 1943044 TI - Children's dietary knowledge, skills, and attitudes: measurement issues. PMID- 1943045 TI - Measuring children's food preferences. PMID- 1943046 TI - Self-report measures of children's physical activity. PMID- 1943048 TI - Observational measures of children's physical activity. PMID- 1943047 TI - Electronic motion sensors and heart rate as measures of physical activity in children. PMID- 1943049 TI - Children's perspectives on exercise and physical activity: measurement issues and concerns. PMID- 1943050 TI - Health-related measures of children's physical fitness. PMID- 1943051 TI - Inhalation efficiency of free-base cocaine by pyrolysis of 'crack' and cocaine hydrochloride. AB - The inhalation efficiency and pyrolysis products of cocaine by the pyrolysis of crack and cocaine hydrochloride at various temperatures are described. The inhalation efficiency of cocaine by the pyrolysis of crack was 73 +/- 9% and 62 +/- 11% at 170 degrees C and 220 degrees C, respectively. When crack was heated at over 225 degrees C, the higher temperature resulted in a lower inhalation efficiency of cocaine. In that case, more methylecgonidine was produced. Furthermore, in the pyrolysis of crack, the lower concentration of cocaine in crack resulted in a lower inhalation efficiency of cocaine. The major pyrolysis product of cocaine HCl was a mixture of alpha, beta, gamma, and delta carbomethoxycyclo-heptatrienes, and the major pyrolysis product of crack was methylecgonidine. This study proposes a new method of discrimination between cocaine HCl and crack by GC or GC/MS with a curie point pyrolyzer. PMID- 1943052 TI - Concentrations of cyclosporin A and its metabolites in human tissues postmortem. AB - We report concentrations and distribution of cyclosporine A (CsA) and individual metabolites associated with various organ tissues and whole-blood specimens collected at autopsy from seven transplant patients who received CsA therapy. Solid-phase extraction (SPE) and specific high-performance liquid chromatographic (HPLC) procedures were used to separate and quantitate the cyclosporines. Patterns of deposition were unique for the various tissue types. Metabolites M17, M1, M18, and M8 (in addition to CsA) were the principal compounds detected in significant quantities. On a per weight basis, the sum concentration of CsA and metabolites in organ tissues was up to 53 times greater than in companion whole blood specimens. Metabolite M17 prevailed in most tissues, except in fat and pancreas, where CsA was predominant. Overall, pancreas specimens contained a greater concentration of cyclosporines (per kilogram of tissue), followed consecutively by spleen, liver, fat, kidney, lung, bone marrow, heart, and whole blood. No CsA-related compounds were detected in brain or spinal cord tissue. PMID- 1943053 TI - A rapid and sensitive quantitation of Amitraz in plasma by gas chromatography with nitrogen-phosphorus detection and its application for pharmacokinetics. AB - We report a simple, sensitive, and rapid quantitation of Amitraz in plasma after Extrelut-3 column extraction by gas chromatography with nitrogen-phosphorus detection (GC-NPD). The plasma sample was diluted four-fold with borate buffer (0.01M, pH 11), put into an Extrelut-3 column, left for 15 min, and then eluted with 15 mL of n-hexane. The n-hexane eluate was evaporated under nitrogen gas flow at room temperature. The residue was reconstituted with 0.1 mL of acetone containing nitrazepam as an internal standard. A 2-microL aliquot was injected into a wide-bore capillary column GC-NPD. The detection limit was 0.5 ng/mL and linearity was obtained in the range of 1-200 ng/mL. Amitraz in the buffer at pH 11 remained stable in a freezer for one week at -20 degrees C. The GC-NPD method was found useful in studying the pharmacokinetics of a single dose intravenous administration of Amitraz to a dog. PMID- 1943054 TI - Simple determination of tin in biological materials by atomic absorption spectrometry with a graphite furnace. AB - A simple and rapid determination of tin in biological materials (blood, brain, liver, kidney, etc,) by atomic absorption spectrometry (AAS) with a graphite furnace is described. Suppression of interferences by direct addition of ascorbic acid in wet-ashed biological materials was investigated for the determination of tin. This method involves no extraction with organic solvent for removal of the interferences, and therefore it is neither time consuming nor error prone, and is suitable for large sample sizes and small sample volumes. The limit of detection of this method is 0.002 microgram/mL, equivalent to a limit of detection in the materials of 0.02 microgram/g. The calibration graph is linear up to 1 microgram/mL of tin. PMID- 1943055 TI - Multicomponent determination of 4-hydroxycoumarin anticoagulant rodenticides in blood serum by liquid chromatography with fluorescence detection. AB - A sensitive liquid chromatographic method was developed for the analysis of 4 hydroxycoumarin anticoagulant rodenticides in blood serum. The method can simultaneously measure the serum levels of five anticoagulant rodenticides: brodifacoum, bromadiolone, coumatetralyl, difenacoum, and warfarin. Serum proteins are precipitated with acetonitrile and the supernatant is mixed with ethyl ether. The organic phase is separated, evaporated to dryness, and the residue subjected to chromatographic analysis. The anticoagulants are separated by reversed-phase gradient chromatography with fluorescence detection at an excitation wavelength of 318 nm and emission wavelength of 390 nm. Extraction efficiencies of 68.1 to 98.2% were obtained. The within-run precision (CV) ranged from 2.19 to 3.79% and the between-run precision (CV) from 3.72 to 9.57%. The anticoagulants can be quantitated at serum levels of 10 to 20 ng/mL. PMID- 1943056 TI - A modification and validation of two urine ethanol procedures for use with the Monarch 2000 Chemistry System. AB - A modification of two commercially available enzymatic ethanol urine assays for use with the Monarch 2000 Chemistry System (Instrumentation Laboratory) is described. Both the Syva EMIT st Urine Ethyl Alcohol Assay and the Sigma Diagnostics Alcohol in Urine Assay, which utilize the reduction of nicotinamide adenine dinucleotide (NAD) to NADH associated with the oxidation of ethanol in the presence of alcohol dehydrogenase (ADH), were adapted to spectrophotometrically determine ethanol concentration. Precision was evaluated over a 3-day period. Within-day (n = 9) and total (n = 27) coefficients of variation (CV) were less than 7% for the controls greater than or equal to 200 mg/L (20 mg/dL). Enzymatic assay results utilizing the Monarch procedure were compared to a gas chromatographic (GC) reference method (n = 100 samples). Regression analysis of assay data with each reagent compared to the reference method resulted in correlation coefficients r = 0.972 (Syva) and 0.948 (Sigma). Both methods exhibited nonlinear results and therefore quantitative applications cannot be made. No false positive or negative results were encountered with either reagent, indicating that the assay is acceptable as a positive/negative screen for urine ethanol for a threshold less than or equal to 20 mg/dL. PMID- 1943057 TI - Analysis of naltrexone and 6-beta-naltrexol in plasma and urine by gas chromatography/negative ion chemical ionization mass spectrometry. AB - A procedure for the analysis of naltrexone and 6-beta-naltrexol in plasma and urine samples is described. The method takes advantage of the specificity of negative ion chemical ionization mass spectrometry and the resolving power of capillary column chromatography to achieve a limit of quantitation of 0.1 ng/mL. The trideuterated analogs of naltrexone and 6-beta-naltrexol are used as internal standards. Samples are first made basic with K2HPO4 buffer (50% w/v), and then extracted twice with n-butyl chloride-acetonitrile (4:1). After back extraction into 0.2 N H2SO4, the samples are again extracted with n-butyl chloride acetonitrile. The extracts are derivatized with 2% methoxyamine in pyridine and pentafluoropropionic anhydride to form the methoxime bis-(pentafluoropropionyl) derivative of naltrexone and the tris-(pentafluoropropionyl) derivative of 6-beta naltrexol. The derivatized extracts are analyzed by selected ion monitoring of prominent ions formed by electron-capture negative ion chemical ionization. PMID- 1943058 TI - Quantification of brodifacoum in plasma and liver tissue by HPLC. AB - A simple high-performance liquid chromatographic method has been developed for detection and quantification of brodifacoum in plasma and liver tissue. After adding difenacoum as the internal standard, brodifacoum and difenacoum are extracted from 2 mL of plasma with two sequential 10-mL volumes of acetonitrile ethyl ether (9:1) and from 2 g of liver tissue by grinding the tissue with 10 mL acetonitrile. The extracts are evaporated to dryness under nitrogen, 2 mL of acetonitrile is added to reconstitute the residues, and the resulting solution is analyzed using reversed-phase chromatography and fluorescence detection. The limits of detection for plasma and tissue are 2 micrograms/L and 5 ng/g, respectively. Using internal standardization, the mean intra-assay recovery from plasma is 92% and the mean inter-assay recoveries is 109%. The mean intra-assay and inter-assay recoveries from tissue are 96%. No interferences were observed with any of the following related compounds: brodifacoum, bromadiolone, coumarin, difenacoum, diphacinone, warfarin, and vitamin K1. PMID- 1943059 TI - Determination of thiosulfate in body fluids by GC and GC/MS. AB - A simple and sensitive method to determine thiosulfate in human blood and urine was devised. Thiosulfate was first alkylated with pentafluorobenzyl bromide, with L-ascorbic acid as the stabilizer and sodium chloride as the catalyst. The alkylated thiosulfate was oxidized with iodine to obtain bis(pentafluorobenzyl)disulfide, which was then subjected to gas chromatography and gas chromatography/mass spectrometry. Mass fragmentography was used to identify the disulfide, and gas chromatography with an electron capture detector was used for quantitative determination. The lower limit of detection was 0.003 mumol/mL. PMID- 1943060 TI - Colchicine poisoning: report of a fatal case with body fluid analysis by GC/MS and histopathologic examination of postmortem tissues. AB - A suicide caused by oral ingestion of colchicine is reported. Postmortem examination revealed circulating Pelger-Huet polymorphonuclear leukocytes and numerous mitotic and chromatin bodies in tissues with rapid cell turnover. Colchicine was identified by gas chromatography/mass spectrometry (GC/MS) of an organic extract of a urine specimen obtained about 36 h after the patient's original hospitalization. The clinical history and pathology of this rarely encountered intoxication are correlated with previous reports, and the rapid detection of colchicine by GC/MS is discussed. PMID- 1943061 TI - Report of a fatal thiamylal intoxication. AB - A fatality due to the intravenous administration of thiamylal is reported. Quantitation of the drug was accomplished by high-performance liquid chromatography (HPLC) and confirmation was by gas chromatography/mass spectrometry (GC/MS). Postmortem tissue concentrations of thiamylal were as follow: 129 mg/L in blood, 366 mg/kg in liver, and 116 mg/kg in brain. Thiamylal was not detected in the urine, gastric contents, or bile. Analytical caveats involving the quantitation of thiamylal are also discussed. PMID- 1943062 TI - Possible formation of ethanol in postmortem blood specimens after antemortem treatment with mannitol. PMID- 1943071 TI - Automated quantitative screening for acidic and neutral drugs in whole blood by dual-column capillary gas chromatography. AB - A method consisting of single-step extraction, dual-channel capillary gas chromatography, nitrogen-selective detection, and automated data processing is evaluated for the quantitative screening of acidic and neutral drugs in postmortem blood. The drugs are identified by their cubic spline retention indices using multidetector retention index standards. The data processing is performed with Micman software, which offers several advantages in the maintenance of identification reliability. The precision of the retention indices during a three-month period with a routine loading of 14 samples per day is presented for eight different drugs at therapeutic and toxic concentrations: The CV ranges from 0.11% to 1.12% for NB-54 and from 0.05% to 0.21% for NB-1701. The within-day CV is less than 0.05% in each case. The status of these results and the means of achieving further precision are discussed. The long-term precision of quantification, normally under 10%, is considered adequate for most forensic toxicological purposes. PMID- 1943066 TI - Influence of elution conditions on HPLC retention index values of selected acidic and basic drugs measured in the 1-nitroalkane scale. AB - The retention indices (RI) of 62 acidic, neutral, and basic drugs were determined by HPLC under isocratic conditions (20, 40, and 60% acetonitrile-phosphate buffer, pH 3.2, containing 0.05% nonylamine) and with gradient elution (5-70% acetonitrile-phosphate buffer pH 3.2, containing 0.05% nonylamine). The RI values of acidic drugs and earlier-eluting basic drugs decreased distinctly with increasing concentrations of acetonitrile. For the later-eluting basic drugs, the opposite trend was observed. The RI data obtained with different isocratic conditions and with gradient elution were not transferable. The study shows the importance of careful standardization of elution conditions for interlaboratory comparison. PMID- 1943063 TI - High concentration of metronidazole in urine invalidates EMIT results. PMID- 1943064 TI - Forensic drug testing for opiates, III. Urinary excretion rates of morphine and codeine following codeine administration. AB - The urinary excretion profile of free and conjugated codeine and morphine was determined by GC/MS for four healthy male subjects after intramuscular administration of 60- and 120-mg doses of codeine. Codeine and metabolites were rapidly excreted with the majority of drug appearing in the first 24 h. No dose related differences in metabolism were observed. The initial ratio of total codeine to total morphine was substantially greater than 1.0 but declined over time. For two of the four subjects, the codeine-morphine ratio declined below 1.0 late in the elimination phase. With a 300-ng/mL cutoff, one subject tested positive on more than one occasion for total morphine and negative for codeine during the terminal elimination phase. The data indicate that urine codeine morphine ratios are not reliable indices of the type of opiate exposure. PMID- 1943065 TI - Direct detection of therapeutic concentrations of tricyclic antidepressants in whole hemolyzed blood using the EMITtox serum tricyclic antidepressant assay. AB - A simple, rapid, and sensitive method for the direct detection of tricyclic antidepressant drugs in whole hemolyzed blood using an enzyme immunoassay technique is described. A methanolic extract prepared from as little as 200 microL of whole blood is analyzed directly using the EMITtox serum tricyclic antidepressant assay, allowing it to be used with whole blood rather than only serum. The minimum detectable concentration of most of the tricyclics is in the range of 25-50 ng/mL, a therapeutic or subtherapeutic, rather than toxic, concentration. The proposed assay shows excellent precision with a mean coefficient of variation (CV) of 0.7%. The cross-reactivity of 12 tricyclic antidepressant drugs is reported. The relationship between drug structure and relative assay response is thoroughly investigated. The relative assay response due to each of nine separate molecular features is calculated. The relationship between the molecular structure and EMIT assay response on a molar basis is shown to be not only quantitative but also additive. This should allow the quantitative prediction of EMIT assay response for drugs or compounds having similar structures. PMID- 1943067 TI - Determination of morphine and codeine in blood and bile by gas chromatography with a derivatization procedure. AB - Two gas chromatographic methods for the simultaneous quantitation of morphine and codeine in blood and bile from cases of opiate-related deaths are described. Both methods employ simple solvent extraction followed by hexane-ethanol partitioning clean-up and use nalorphine as the internal standard. The first method relies on the formation of trimethylsilyl derivatives and detection with a nitrogen phosphorous detector. The second method involves the formation of heptafluorobutyryl derivatives and detection with an electron capture detector. Both methods are sensitive, able to detect down to 0.04 microgram/mL of morphine and 0.1 microgram/mL of codeine. Their wide linear dynamic ranges cover from low therapeutic to lethal levels for both morphine and codeine. The methods are amenable to batchwise operation and each analysis can be completed within three hours. The results of both methods correlate very well. The trimethylsilyl derivatives can be hydrolyzed and rederivatized for form heptafluorobutyryl derivatives for the second method, which then serves to confirm the results of the first method. Pholcodine, another common opiate, can likewise be determined. Average recovery was 80% for blood morphine and codeine and 60% for bile morphine and codeine. PMID- 1943069 TI - Solid-phase extraction of a carcinogen, 4,4'-methylenedianiline, in serum. AB - Polyurethane (PU) is a material used to make medical devices. During the gamma ray or autoclave sterilization of these medical devices, PU degrades and a carcinogen, 4,4'-methylenedianiline (MDA), is produced. We studied a pretreatment method for MDA in blood serum by solid-phase extraction. Using Bond Elut C18, phenyl, and cyclohexyl columns, MDA in serum at a concentration of 0.1-10 ppm was 100% recovered with no apparent difference between the columns tested. Elution was carried out with methanol containing 1M MH4OH. The recovery rate of serum MDA with a Bond Elut C8 column was 90%, less than that from the above columns. The recovery of serum MDA from Bond Elut C1, C2, and silica was unsatisfactory. The recovery rate with Bond Elut SCX (strong cation exchange column) proved satisfactory, but the pretreatment of serum was troublesome as both deproteinization and centrifugal separation procedures were necessary in addition to the complicated conditioning procedure of the SCX column. There was no significant difference in recovery rate among C18, phenyl, and cyclohexyl columns, indicating that both pi-pi binding between benzene rings and van der Waals binding would be predominant. Because Bond Elut silica showed a lower recovery rate, the binding of NH2 in MDA with free silanol would not be predominant. PMID- 1943070 TI - Plasma determination of flumazenil, a benzodiazepine antagonist, by immunotoxicology and by capillary gas chromatography/mass spectrometry. AB - The method presented describes a sensitive and specific quantitative assay for the determination of flumazenil in human plasma. Flumazenil and an internal standard, midazolam, are isolated by a basic extraction. The final extract is separated on a 25-m BP-1 capillary column and drugs are detected by selected ion monitoring at m/z 229 and m/z 310 for flumazenil and the internal standard, respectively. The minimum detectable quantity is 1.0 ng/mL, for flumazenil in plasma. Coefficients of variation for within-run data were less than 6%. PMID- 1943068 TI - Standardized HPLC/DAD system, based on retention indices and spectral library, applicable for systematic toxicological screening. AB - An HPLC gradient elution system is applied for general toxicological screening. The use of a diode array detector with library software allows storage of retention parameters, UV spectra, and peak quality parameters of examined substances. The developed library is used for automatic identification of compounds. The retention indices of 225 substances are measured in the 1 nitroalkane scale. These data may be of interlaboratory use because of an appropriate correction procedure. Long-term reproducibilities of retention behavior of 1-nitroalkanes and correction standards are satisfactory. The conditions of interlaboratory use are discussed. PMID- 1943072 TI - GC/MS analysis of propylated barbiturates. AB - A simple and reproducible method for the analysis of barbiturates by GC/MS after derivatization with dimethylformamide dipropyl acetal is reported. The method is readily adapted to screening, confirmation, and quantitation. PMID- 1943073 TI - Scopolamine poisoning from homemade 'moon flower' wine. AB - LH, a 76-year-old Caucasian male, ingested 3 teaspoons (15 mL) of a homemade wine over a 1-h period and became ill. Approximately 1.5 h later, he was taken to the emergency room of a local hospital with symptoms of respiratory distress and weakness. The plant used in making the wine was Angel's trumpet (Datura suaveolens), which reportedly contains varying amounts of scopolamine and atropine. A sample of the wine was collected and analyzed for these two compounds by reversed-phase HPLC chromatography using 97% methanol-3% deionized water. The filtered wine contained an estimated 29 mg scopolamine/mL, which produced a total ingested dose of 435 mg. No atropine was detected. The scopolamine was confirmed by TLC. An oral dose of 50 mg of atropine sulfate in humans has been reported fatal, but there is no reported fatal dose for scopolamine. The alcohol content and 3.8 pH of the homemade wine may have increased the extraction of this compound from the plant material, and the wine fermentation process may have concentrated the original extract. PMID- 1943074 TI - Reply to 'Incorrect reanalysis of breath/blood alcohol data'. PMID- 1943075 TI - The relevance of urinary cocaethylene following the simultaneous administration of alcohol and cocaine. PMID- 1943076 TI - Death anxiety in Japan and Australia. AB - This study compared death anxiety ratings as measured by the Templer Death Anxiety Scale (Templer, 1970) in 121 Japanese and 139 Australian subjects. Japanese subjects had significantly higher death anxiety scores than their Australian counterparts. Australian women scored significantly higher than Australian men, but no sex differences were found in the Japanese sample. A slight but statistically significant positive correlation was found between age and death anxiety scores. This study contradicted other research that indicated that Eastern cultural attitudes mitigated anxiety about death. These findings are discussed in relation to the complex relationship between culture and death anxiety as well as in relation to problems inherent in our current conception of death anxiety. PMID- 1943077 TI - Determinants of the acceptance of co-workers with AIDS. PMID- 1943078 TI - Locus of control, depression, and anger among Native Americans. PMID- 1943080 TI - The factor structure of the Aging Semantic Differential: a failure to replicate Rosencranz and McNevin. PMID- 1943079 TI - Effects of cranial and facial hair on perceptions of age and person. PMID- 1943084 TI - Alteration in Ca2+ homeostasis by a trauma peptide. AB - Postinjury tissue inflammation with PMN elastase proteolysis generates immunosuppressive fibronectin peptides (FNDP) impairing chemotaxis, T-cell activation, and proliferation. Excess intracellular Ca2+ ([Ca2+]i) impairs T-cell activation. This study quantifies the changes in [Ca2+]i following exposure to a degradation peptide of fibronectin to determine the mechanism of action of these peptides on calcium homeostasis. Isolated human PBLs were exposed to immunosuppressive concentrations of FNDP after loading with the [Ca2+]i probe FURA-2AM. Resting and sustained [Ca2+]i concentrations were calculated and compared to buffer control. The mechanism of action was determined by pretreatment with: (1) EDTA binding extra cellular Ca2+: [Ca2+]e, (2) the Ca2+ channel blockers verapamil and nifedipine, and (3) inhibition of [Ca2+]i released by dantrolene. Inositol triphosphate (IP3) essential for [Ca2+]i release was measured following T-cell stimulation as well. FNDP caused 200-400% increases in [Ca2+]i concentration relative to buffer control at known suppressive doses. Verapamil and nifedipine partially block [Ca2+]i influx by as much as 50% suggesting the slow Ca2+ (voltage independent) channels are partially responsible for the increased [Ca2+]i seen following FNDP. EDTA completely suppressed [Ca2+]e influx but did not completely inhibit the release of [Ca2+]i although IP3 was 80% suppressed. The increase in [Ca2+]i following FNDP stimulation is due to release of intracellular stores. PMID- 1943081 TI - Cell cycle parameters and DNA ploidy in colorectal carcinomas. AB - Seven patients with colorectal adenocarcinoma and one with squamous cell carcinoma of anorectal region were infused preoperatively with iododeoxyuridine (IUdR) and bromodeoxyuridine (BrdU) in sequence (100 mg/m2 x 1 hr each with 1-hr interval in between) to label S-phase cells. The tumor biopsy specimens were embedded in glycol-methacrylate and 2-microns thick sections were treated with two monoclonal antibodies which permitted the identification of cells which incorporated IUdR only, BrdU only, both IUdR and BrdU, or neither IUdR or BrdU. The labeling index of tumors varied from 17.3 to 35.6% (mean = 25.78 +/- 6.162), duration of S-phase ranged from 14.0 to 23.9 hr (mean = 18.73 +/- 3.712), and total cell cycle time ranged from 39.4 to 123.4 hr (mean = 76.78 +/- 24.165). The architecture of the tumor was well preserved and a variable number of DNA synthesizing mononuclear cells were identified within and around the tumor. Image analysis of Feulgen-stained smears of the tumors was done to measure the DNA content of seven tumor samples. Each tumor was found to be hyperdiploid with multiple modal values. The studies described here demonstrate the feasibility of performing cell cycle kinetic measurements on gastrointestinal tumors which have been labeled in vivo. The ability to perform these measurements on tumor biopsies allows the avoidance of artifacts introduced when solid tumors are disaggregated in vitro for study. PMID- 1943083 TI - Insulin-like growth factor-I response is comparable following intravenous and subcutaneous administration of growth hormone. AB - Subcutaneous (sq) administration of recombinant human growth hormone (r-hgh) has an anabolic effect and increases systemic insulin-like growth factor (IGF-I) in surgical patients. IGF-I is a mediator of growth hormone (gh) anabolic effects. To determine the effect of intravenous (iv) administration of r-hgh on systemic IGF-I, 11 patients were given 14 1-week courses of daily 8-hr infusions of r-hgh (10 mg in 500 ml D5W). Serum gh and IGF-I levels were measured. To compare routes of administration, iv r-hgh patients were matched to comparable sq r-hgh patients and IGF-I responses were examined. Illness severity effect on IGF-I response to r hgh was assessed by dividing 16 burn patients who received either iv or sq r-hgh into two groups on the basis of severity scores. Analysis of the data showed that IGF-I levels increased significantly after iv r-hgh, IGF-I response to iv r-hgh (1.14 +/- 0.18 U/ml to 4.12 +/- 0.65 U/ml) was not different from IGF-I response to sq r-hgh (1.04 +/- 0.36 U/ml to 4.96 +/- 1.09 U/ml). Increasing illness severity attenuated the IGF-I response in the more severely injured group (0.91 +/- 17 U/ml to 2.40 +/- 0.38 U/ml) relative to the less severely injured group (1.37 +/- 0.22 U/ml to 5.53 +/- 0.78 U/ml) despite a significant increase in IGF I after gh in both groups. In summary, IGF-I increased significantly after iv r hgh and the increases were similar to those seen after sq r-hgh in comparable patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943082 TI - Hepatocellular oxidant stress following intestinal ischemia-reperfusion injury. AB - Reperfusion of ischemic intestine results in acute liver dysfunction characterized by hepatocellular enzyme release into plasma, reduction in bile flow rate, and neutrophil sequestration within the liver. The pathophysiology underlying this acute hepatic injury is unknown. This study was undertaken to determine whether oxidants are associated with the hepatic injury and to determine the relative value of several indirect methods of assessing oxidant exposure in vivo. Rats were subjected to a standardized intestinal ischemia reperfusion injury. Hepatic tissue was assayed for lipid peroxidation products and oxidized and reduced glutathione. There was no change in hepatic tissue total glutathione following intestinal ischemia-reperfusion injury. Oxidized glutathione (GSSG) increased significantly following 30 and 60 min of reperfusion. There was no increase in any of the products of lipid peroxidation associated with this injury. An increase in GSSG within hepatic tissue during intestinal reperfusion suggests exposure of hepatocytes to an oxidant stress. The lack of a significant increase in products of lipid peroxidation suggests that the oxidant stress is of insufficient magnitude to result in irreversible injury to hepatocyte cell membranes. These data also suggest that the measurement of tissue GSSG may be a more sensitive indicator of oxidant stress than measurement of products of lipid peroxidation. PMID- 1943087 TI - Attenuation of histamine-induced lymphatic smooth muscle contractility by arachidonic acid. AB - Recent investigations have identified a class of outwardly rectifying potassium channels activated directly by arachidonic acid (AA) and select other fatty acids (FA) that inhibit smooth muscle contractions. We hypothesized that lymphatic smooth muscle contains similar fatty acid activated channels. Fresh porcine tracheobronchial lymphatic vessel rings were mounted in organ baths and connected to force-velocity transducers. Contractile responses were measured following exposure to histamine alone, with AA, and following AA washout, demonstrating a 40-55% inhibition of histamine-induced contractility by AA. Despite addition of indomethacin and nordihydroguaiaretic acid to inhibit formation of active AA metabolites, AA still attenuated contractility by 24-31%. Myristic acid and linoelaidic acid, FA's that are not substrates for cyclooxygenase or 5 lipoxygenase, inhibited histamine-induced contractility by 19 and 15%, respectively. The effects of AA and the other FA's were eliminated by exposure to a high potassium solution. The data support the existence of AA-activated hyperpolarizing potassium channels in lymphatic smooth muscle. Arachidonic acid, in addition to its metabolites, may play a direct role in regulating lymphatic smooth muscle tone. PMID- 1943086 TI - Anti-tumor necrosis factor antibody augments edema formation in caerulein-induced acute pancreatitis. AB - The pathogenesis of acute pancreatitis is incompletely defined, but the outcome is determined in part by an acute inflammatory process. Pancreatitis-associated inflammation appears to play a role in the local retroperitoneal injury as well as in the associated dysfunction of remote organs such as the lung. Tumor necrosis factor (TNF) appears to be a proximal mediator of the inflammatory response. In this study, anti-TNF antibody was administered to rats with caerulein-induced pancreatitis to determine if the observed increases in pancreatic and pulmonary microvascular permeability were related to plasma TNF activity. In contrast to the expected findings, blockade of TNF activity was found to increase the amount of edema formation in both the pulmonary and pancreatic microvascular beds. The mechanism is not known; however, blockade of TNF-induced down regulation of phagocytic cell activity, ablation of TNF dependent feedback inhibition of other cytokines, failure of induction of endogenous antioxidant systems, or inactivation of the TNF control of microvascular tone are all possible explanations. This is potentially an important observation as clinical strategies are now being developed to modify the inflammatory response in ways presumed advantageous to an injured host. PMID- 1943088 TI - Propagation of small bowel migrating motor complex activity fronts varies with anastomosis type. AB - Fasting small intestine motility (migrating motor complex or MMC) occurs in humans and dogs in four phases. Activity fronts during phase III consist of high amplitude contractions propagating aborally and are interrupted by transection of the small intestine. To study the effect of anastomosis type on MMC propagation six dogs underwent resection of a 15-cm segment of bowel 45 cm distal to the ligament of Treitz and single layer hand sewn end-to-end (EE) anastomosis. Single layer end-to-side (ES) or side-to-side (SS) anastomoses were hand sewn 15 cm distal to the transection in six other dogs. Eight force transducer strain gauges were placed at 10-cm intervals about each anastomosis. At least 7 days after operation, small bowel contractions were recorded in fasted animals, and recordings were visually inspected. Only 1 of 36 activity fronts propagated across the end-to-end anastomosis within 45 days of surgery. However, after 60 days 25 of 39 phase III activity fronts propagated. There was no propagation of MMC activity across the ES anastomosis and only 10% of activity fronts propagated across the SS anastomosis. We conclude phase III MMC activity front propagation is interrupted by small bowel transection. Propagation regenerates after EE anastomosis, but not after ES or after SS anastomoses, even after prolonged healing. PMID- 1943089 TI - Small bowel transplantation promotes bacterial overgrowth and translocation. AB - Alterations in the symbiotic relationship between immunocompromised hosts and their resident gut microflora may lead to serious complications following small bowel transplantation (SBT). This study examined the effects of SBT and cyclosporine (CsA) immunosuppression on gut bacterial populations and translocation to the mesenteric lymph nodes. Sixty adult male meat-fed Lewis rats were divided into six groups: normal controls, CsA alone (24 mg/kg im qod), CsA carrier vehicle alone, isografts, isografts given CsA, and allografts given CsA. Rats were killed after 3 weeks and segments of small bowel and colon were harvested for quantitative tissue culture. Mesenteric lymph nodes and blood were cultured to identify translocation. Transplantation alone led to an increase in gram-negative aerobes from 2.6 to 4.6 colony forming units/100 mg tissue (P less than 0.05) in the distal ileum (transplanted segment). Eighty-four percent of transplanted animals receiving CsA had bacteria recovered from their mesenteric lymph nodes compared to none in controls (P less than 0.001) and 20% in isografts not receiving CsA (P less than 0.02). Intestinal transplantation alone appears to promote gram-negative overgrowth while the addition of CsA therapy facilitates translocation to the mesenteric lymph nodes and may predispose to gut-associated sepsis following SBT. PMID- 1943091 TI - The effect of hypercholesterolemia on early atherosclerotic lesions initiated by fibrinopeptide B. AB - Hypercholesterolemia and thrombosis have been implicated as factors in the development of atherosclerosis. Fibrinopeptide B (FPB) is a short chain peptide cleaved from fibrinogen during the production of fibrin. FPB is a known chemoattractant and has been shown to produce experimental atherosclerotic lesions in association with hypercholesterolemia. The present study was designed to examine the role of hypercholesterolemia in this process and to study the time course of the development of these lesions. Twelve New Zealand White rabbits were placed on an atherogenic diet and had suture carrying either FPB, fibrinopeptide A (FPA), or saline (controls) implanted in the adventitia of the femoral arteries and were sacrificed at 14 days. An equal number of animals were left on a standard diet and underwent similar treatment. Eleven animals were treated as the hypercholesterolemic group but were sacrificed at 2, 4, and 7 days. The thickness of the intima was measured adjacent to the suture in the animals sacrificed at 14 days, and the hypercholesterolemic FPB sites were thicker (12.23 mu +/- 6.60) than either hypercholesterolemic FPA (6.06 mu +/- 3.72), saline (4.94 mu +/- 1.42), or the normocholesterolemic FPB (5.99 mu +/- 4.61), FPA (3.89 mu +/- 2.20), or saline (3.97 mu +/- 1.83) (P less than 0.05 for all groups). Transmission electron microscopy of the hypercholesterolemic FPB group showed evidence of macrophages, actively secreting smooth muscle cells with newly deposited elastin, and foam cells by 7 days. We conclude that FPB attracts or stimulates macrophages and smooth muscle cells and that the resultant cellular and extracellular proliferation favors early atherosclerotic lesion formation in the presence of hypercholesterolemia. PMID- 1943092 TI - Reconstructive periodontal plastic surgery. PMID- 1943085 TI - Changes in aortic levels of tropoelastin mRNA following treatment of rats with the antihypertensive drugs captopril and hydralazine. AB - This manuscript describes changes in the steady state levels of aortic tropoelastin mRNA in spontaneously hypertensive rats (SHR) and normotensive controls (WKY) following treatment with two antihypertensive drugs. Three-week old WKY and SHR rats were treated with hydralazine (15 mg/kg/day) or captopril (25 mg/kg/day). Tail artery blood pressure was monitored twice weekly. Both drugs prevented the development of hypertension in the SHR rat. At 6 weeks of age, total aortic RNA was extracted and the steady state levels of mRNAs coding for tropoelastin and pro alpha 1 (III) collagen were determined by slot blot hybridization analysis using radiolabeled tropoelastin and pro alpha 1 (III) collagen cDNA clones. Hydralazine treatment resulted in a threefold increase in tropoelastin mRNA levels in both the SHR and the WKY animals (P less than 0.01). Captopril-treated SHR animals demonstrated a similar significant increase. In contrast, no differences in pro alpha 1 (III) collagen mRNA levels were observed in the aorta of SHR or WKY rats following treatment with either captopril or hydralazine. These data suggest that antihypertensive agents can act specifically to directly induce tropoelastin mRNA levels in large arteries and thus may induce vascular remodeling independent of an increase in blood pressure. PMID- 1943090 TI - Effect of exogenous growth hormone on glucose utilization in burn patients. AB - The treatment of burn patients with recombinantly derived human growth hormone (rHGH) appears effective in counteracting protein catabolism. However, exogenous growth hormone is frequently associated with hyperglycemia, an aspect which may limit its usefulness. Therefore, to assess the affect of rHGH on glucose utilization, 13 severely burned patients (65% +/- 4 TBSA burn; mean +/- SEM) began receiving on admission either placebo or rHGH (0.2 mg/kg.d) in a double blind randomized fashion. While hypermetabolic (percentage REE/predicted REE 1.41 +/- 0.11) fasting oxygen consumption and CO2 production were measured using indirect calorimetry prior to and then during a hyperinsulinemic euglycemic clamp. This experiment demonstrated that rHGH significantly reduced glucose uptake and inhibited glucose oxidation compared to the placebo patients. Since the decreases in glucose oxidation and uptake were proportional, glucose utilization (percentage glucose uptake oxidized) remained similar in both patient groups. Furthermore, the hyperinsulinemic clamp lowered the plasma amino acid concentrations in the control patients while rHGH-treated patients had no significant alterations. In conclusion, exogenous growth hormone therapy induces an insulin resistance in burn patients. Furthermore, since the glucose utilization did not change, it is likely that the mechanism of insulin resistance is due to a deficiency in glucose transport. PMID- 1943096 TI - The temporal patterning of tension reduction: stress and alcohol use on weekdays and weekends. AB - A sample of 328 students provided reports of drinking episodes and ratings of situational stress experienced during two series of 4-hour time blocks covering early and late evening hours on weekdays (Tuesday and Wednesday) or weekends (Friday and Saturday). Although baseline levels of "predrinking" stress were not strongly related to the onset of drinking episodes in subsequent time blocks, analyses of temporal changes in stress from "predrinking" to "drinking" blocks show a significant tension-reduction effect among respondents who used alcohol- in contrast to those who did not drink--on both weekday evenings and early Friday evening (4-8 PM). No significant changes in stress ratings occurred among late Friday or Saturday evening drinkers. Multivariate analyses indicate that the weekday tension reduction effect is not systematically contingent on questionnaire measures of individual characteristics (age, sex, coping motives and typical drinking patterns) nor on situational measures of consumption and intoxication. The results suggest that weekday drinking after work or class is a culturally defined occasion for "time out" from stress. PMID- 1943095 TI - Alcohol abusers' and social drinkers' responses to alcohol-relevant and general situations. AB - Responses of alcohol abusers and social drinkers were compared on general and alcohol-specific problem situations using role-play methodology. Multiple responses were assessed including behavioral observational ratings, self-reports and psychophysiologic measures. There were few differences between groups in responses to the general situations. Alcohol abusers had higher urges to drink than did the social drinkers in both the general and the alcohol-specific situations. However, in response to the alcohol-specific situations, the alcohol abusers, compared to the social drinkers, were rated by judges as significantly less skillful, and they displayed more self-reported anxiety, had a higher frequency of occurrence of problem situations in the natural environment and reported greater perceived realism of the alcohol-specific situations. Psychophysiologic measures did not differentiate between the groups. Results are discussed with respect to the importance of situation specificity in understanding the precipitants of drinking and their treatment implications. PMID- 1943098 TI - Marriage and alcohol use: a longitudinal study of "maturing out". AB - Earlier findings have suggested that marriage may provide protection from a variety of physical and psychological problems. In particular, numerous studies have demonstrated a consistent relationship between marital status and alcohol use. To examine this relationship more carefully, we performed a longitudinal analysis of data collected on the Youth Cohort of the National Longitudinal Survey of Labor Market Experience. Four marital transition groups were constructed based upon marital status across a 3-year period: stably single, married year 3, married year 2 and stably married. Results of repeated-measures MANCOVAS performed on alcohol-use patterns across time as a function of marital transition group supported the notion that individuals begin moderating their alcohol consumption prior to their actual transition to married status with the trend continuing into the first year of marriage. The data further suggested that this decline in alcohol use stabilizes shortly thereafter, apparently within 1 year after marriage. PMID- 1943094 TI - Antecedents of drinking among young adolescents with different alcohol use histories. AB - Testing separate path analytic models for 7th-grade users and nonusers, we assess the impact of cognitive, social influence and behavioral antecedents on adolescent drinking 3 and 12 months later. For the group that had not tried alcohol by grade 7, we found that social influence factors--exposure to peers who drink or use marijuana and to adults who drink--foster more frequent alcohol use and binge drinking in the near future (3 months later). The key peer influences on binge drinking were marijuana-specific. After 12 months, the child's own drinking experience during grade 7 and peer and parental attitudes toward drugs emerge as important explanatory variables. For children who had already started drinking by grade 7, cognitive--as well as social and behavioral factors--affect near- and longer-term alcohol involvement. While the child's prior drinking habits have the strongest impact, baseline expectations of using alcohol also predict frequency of alcohol use and binge drinking after 3 and 12 months. Believing that alcohol use is harmful helps hold down increases in frequency of use (but not excessive use) as long as 12 months later. Engaging in deviant behavior or doing poorly in school did not predict future drinking among baseline nonusers, but did foretell which of the 7th-grade initiates were most likely to engage in binge drinking during grade 8. The study's implications for prevention are discussed. PMID- 1943093 TI - Factors influencing the effectiveness of server-intervention education. AB - The purpose of the study was to assess the effect of server-intervention education and the effect of various situational variables upon program effectiveness. A 6-hour server education program was administered to 876 servers and 203 managers of 100 licensed establishments in eight states. Participants in the program were administered knowledge, attitude and behavior self-report measures prior to and following the program. Each establishment was also visited three to four times, before and after the program, by staff observers exhibiting visible signs of intoxication. Equal numbers of visits were also made to a comparison group of 138 establishments in the same communities as the establishments participating in the program. Significant improvement in knowledge, attitude and self-reported behavior was found among program participants. A significant overall increase in observed intervention was found in visits to participating establishments and no change was found within the comparison group. However, there was a significant intervention-by-state interaction with positive changes occurring in only five of the eight states. Differences among states in observed intervention were not related to dram shop law, but did appear to be related to prior level of intervention, type of establishment and business volume. Unfortunately, even after training, intervention was observed in only 20% of the 1,590 visits, and only 7% of the visits resulted in terminating service. The lack of incentives for discontinuing service to intoxicated patrons is discussed. PMID- 1943099 TI - Sexual satisfaction and dissatisfaction in the marital relationships of male alcoholics seeking marital therapy. AB - Twenty-six married couples with alcoholic husbands who sought marital therapy were compared with two groups of couples without alcohol-related problems, 26 couples with marital conflict (MC) and 26 with no marital conflict (NC), on a range of sexual satisfaction variables. As predicted, the alcoholic and MC couples did not differ and both of these groups of couples reported less sexual satisfaction than the NC couples. Alcoholic and MC couples, in comparison with NC couples, reported less frequent intercourse, more change desired in intercourse frequency, greater misperception about the amount of change in sex frequency desired by their mate and more disagreement about sex. In addition, the finding that older alcoholics had less frequent intercourse replicated similar results by Jensen. Limitations of the present research and needed future research are discussed. PMID- 1943100 TI - Degrees of alcohol intoxication in 117 hospitalized cases. AB - The correlation among degrees of alcohol intoxication, facial flushing, blood alcohol concentration (BAC) and blood acetaldehyde level was studied in 117 male alcoholic patients who underwent various tests to assess alcohol influence. Blood samples were collected and alcohol and acetaldehyde levels were determined. BACs ranged from 29 to 577 mg/dl in all patients and from 200 to 299 mg/dl in 48 of them. Fifty-one patients could stand erect (mean BAC [+/- SD] = 189 +/- 80 mg/dl), while 48 showed apparently normal reaction to a walking and turning test (mean BAC = 192 +/- 78 mg/dl). Some of the cases having BACs over 300 mg/dl could still stand and walk while others with BACs under 100 mg/dl already showed psychomotor impairment. Facial flushing was recognized in 75% of the subjects. Acetaldehyde concentrations in 27 patients ranged from 24 to 147 micrograms/dl. Appearance of facial flushing was correlated with relatively high concentrations of blood acetaldehyde. Seven out of 10 healthy volunteers given 1.6 to 2.0 g/kg of alcohol as a control could do nothing but sleep after reaching peak BAC (mean = 232 +/- 21 mg/dl). These findings are taken to indicate a great difference in response to alcohol between alcoholics and healthy men. This study is the first to report the occurrence of facial flushing and raised blood acetaldehyde concentration among Japanese alcoholics. PMID- 1943102 TI - High levels of sensitivity to alcohol in young adult Jewish men: a pilot study. AB - This article compares the intensity of response to ethanol in 15 men who reported having Jewish mothers and fathers with the responses of 15 non-Jews who have a close alcoholic relative (FHP) and 15 non-Jews who have no such family history (FHN). After matching the three groups on demography and drinking history, there were no differences on their expectations of the effects of alcohol, nor on the blood alcohol concentrations following the consumption of 0.75 ml/kg of ethanol. However, the men who considered themselves as having a Jewish heritage evidenced significantly more intense subjective feelings after the alcohol challenge, with a similar but nonsignificant trend observed for their level of postdrinking body sway. PMID- 1943097 TI - The inheritance of alcohol consumption patterns in a general population twin sample: II. Determinants of consumption frequency and quantity consumed. AB - Genetic models were fitted to self-report data on frequency of alcohol consumption and average quantity consumed when drinking, from 3,810 adult Australian twin pairs. Frequency of consumption is determined both by an abstinence dimension, which is strongly influenced by shared environmental effects but not by genetic effects, and by an independent frequency dimension, which is influenced by genetic effects in both sexes and possibly by shared environmental affects in men. Quantity of alcohol consumed is likewise determined by an environmental abstinence dimension and by an independent and partly heritable quantity dimension. The best-fitting model allowed for two routes to abstinence: those who were not abstainers by virtue of their position on the abstinence dimension could nonetheless become abstainers by their position on the second, frequency (or quantity) dimension. Heritability estimates were 66% in women and 42-75% in men, for frequency; and 57% in women and 24-61% in men, for quantity. PMID- 1943101 TI - "Machismo," self-esteem, education and high maximum drinking among anglo, black and Mexican-American male drinkers. AB - This study seeks to clarify the relevance of machismo to patterns of high maximum drinking among male drinkers. Specifically, the study describes the psychometric properties of a newly developed 7-item machismo measure, compares levels of machismo and self-esteem for a sample of Anglo, black and Mexican-American males, and examines both main and interaction effects of machismo, self-esteem and education as predictors of alcohol use in these racial/ethnic subgroups. Logistic regression analyses document interaction between race/ethnicity, machismo, self esteem and education, which calls into question the presumed importance of machismo as a cultural element causing heavy drinking patterns among Mexican American males. PMID- 1943104 TI - A new method of breath testing the general driving population. AB - The efficacy of drinking-driving countermeasures can be assessed in several ways, including reported changes in attitudes and behavioral intent as well as changes in crash rates. However, few studies have examined the changes in actual drinking driving behavior. A method of surveying the blood alcohol concentrations (BACs) of drivers, without either police intervention or disruption to traffic flow, was developed in South Australia. This method, which has been used successfully to test approximately 50,000 drivers, is described in detail. PMID- 1943106 TI - Ethanol's effects on tremor and positioning in squirrel monkeys. AB - Ethanol ingestion markedly reduces tremor in patients with essential tremor. This clinical observation prompted the present experiments, which were designed to investigate ethanol's reduction of tremor in squirrel monkeys trained to execute a bar-holding task. A lever was attached to the hub of a rotary variable differential transformer (RVDT) and three squirrel monkeys were trained to position this lever within a 4.5 cm band for 8 seconds for a fruit juice reward. Behavior was maintained by a random ratio 2 schedule of reinforcement. Angular position of the lever was sampled for 5.12 seconds while the monkey held the bar, differentiated twice and analyzed to obtain a spectral description of tremor in units of acceleration 2/Hz. During control and vehicle sessions a spectral peak appeared at about 6-8 Hz and the magnitude of this peak varied from 25 to 150 milli-g2/Hz (where g is the acceleration due to gravity). A second peak appeared in two animals at greater than 15 Hz. For one animal this high-frequency peak was dominant during control sessions but the 6-8 Hz peak was dominant after intubation with water or ethanol. Ethanol produced consistent and dose-related decreases in the amplitude of the spectrum describing tremor but the location of the spectral peaks did not differ from vehicle sessions. The doses that altered tremor also produced an increase in the number of short-duration holds as well as other, less consistent, alterations in the form of the response. These data confirm and quantify ethanol's potency as a tremorolytic agent. PMID- 1943103 TI - Prior exposures to the laboratory enhance the effect of alcohol. AB - We compared responses to 0.6 g/kg alcohol of normal male drinkers in a laboratory environment that was new to the subjects with the responses of a second group in the same environment who had two prior exposures to the laboratory environment and procedures. Alcohol-induced increases in heart rate, cheek temperature and self-reported intoxication were greater in the subjects who had previous exposure to the laboratory environment than in the subjects who had no such previous exposure. Differences in blood alcohol concentration (BAC) also were found between the two environments. However, differences in the physiological and self report measures were found after matching subjects in terms of BAC. These results suggest that novelty effects may contaminate alcohol responses in novel laboratory environments, and they add to our understanding of nonpharmacological factors in the responses to drugs. PMID- 1943109 TI - Is there an established role for immunotherapy for any of our surgical cancers? PMID- 1943107 TI - Measuring alcohol consumption: a comparison of the retrospective diary and the quantity-frequency methods in a college drinking survey. AB - As part of a larger study of college drinking, the quantity-frequency (Q-F) measure of alcohol consumption was compared to the retrospective diary (RD) method with 494 drinkers out of 606 respondents (75.8%) of 800 randomly selected undergraduates. Respondents were representative by sex and year in school of virtually all full-time undergraduates at Rutgers, the State University of New Jersey. The study tested the hypothesis that the RD would yield higher estimates of average alcohol consumption and of "heavy drinking" as defined by NIAAA typology (average two or more drinks per day) and of "peak drinking," a Q-F standard consisting of five or more drinks at least once per week. The study also compared the two methods as correlates of self-reported problems related to drinking. Results supported the major hypotheses that the RD would detect more overall consumption, heavy drinking and peak drinking than the Q-F. Results also demonstrated good consistency between the Q-F and RD as well as comparable correlations with the alcohol problem score. PMID- 1943108 TI - Measurement of ethanol consumed in distilled spirits. PMID- 1943105 TI - Effects of minimum drinking age laws on alcohol use, related behaviors and traffic crash involvement among American youth: 1976-1987. AB - This study has two separate but related purposes: (1) to delineate cross sectional differences among U.S. high school seniors and young adults that may be due to variations in recent years in state-level minimum drinking age laws and (2) to examine the effects of recent changes in minimum drinking age laws on alcohol consumption and other relevant attitudes and behaviors. Analyses used existing data collected by the Monitoring the Future project, an ongoing study involving annual, nationally representative surveys of high school seniors and annual follow-up surveys by mail of recent graduates. A separate, coordinated study used time-series analyses of official reports to examine effects of increases in the minimum drinking age in several states on rates of fatal crashes. Time-series results were compared with findings from self-report data. The major findings include: higher minimum drinking ages were associated with lower levels of alcohol use among high school seniors and recent high school graduates, even after multivariate controls; lower levels of alcohol use were observed across a number of demographic variables; the lower levels of use persisted into the early 20s, even after all respondents were of legal age; and lowered involvement in alcohol-related fatal crashes among drivers under 21 appeared due to lower alcohol consumption rates--in particular, less drinking in bars or taverns. PMID- 1943110 TI - Survival of patients with metastatic breast cancer diagnosed between 1955 and 1980. AB - In order to determine whether current programs for the management of metastatic breast cancer have led to improved patient survival, we determined the median survival times for five-year intervals of 849 patients admitted to the City of Hope National Medical Center with metastatic breast cancer from 1955 to 1980. Survival curves were constructed from the dates of first diagnosis of breast cancer and to the first metastasis for all population subsets and clinical subsets: menopausal status, presence or absence of visceral metastases, length of disease-free interval, and pattern of palliative therapy. In this analysis, the median survival in each successive interval of five years from diagnosis of the primary tumor was 52.1, 45.0, 49.9, 41.1, and 36.0 months, and the survival times from the first metastasis were 31.9, 23.0, 24.2, 23.9, and 18.7 months. Survival times in each of the clinical subsets remained unchanged during the period of observation, regardless of the therapeutic modalities included in the treatment regimens. This study indicates that changes in palliative therapy for metastatic breast cancer during the 25 years of observation have not influenced overall survival. Therefore, it seems appropriate that the therapeutic risk/benefit ratio and impact on quality of life should be reassessed when asymptomatic patients are treated, or when aggressive palliative therapy is used outside a clinical research setting. PMID- 1943112 TI - Subtotal submucosal cricoid resection: an experimental study. AB - It has generally been considered that the cricoid cartilage is essential for maintaining airway continuity. The purpose of this experimental study was to test this concept by evaluating the effects of subtotal excision of the canine cricoid cartilage. Eight adult mongrel dogs were studied. They received general anesthesia and were intubated. By using a vertical midline incision, the cricoid cartilage was exposed. Subtotal cricoid resection was performed by submucosal dissection; the mucosal continuity was not violated. The resultant defect in the cricoid cartilage was reconstructed with a polytetrafluoroethylene (PTFE) graft which was sutured in place with prolene sutures. All the dogs were extubated immediately after surgery. None required tracheostomy or ventilatory support and none had any respiratory problems during the follow-up period. They were all able to eat soon after surgery. The animals were followed for up to 4 to 6 months and then sacrificed to permit evaluation of the condition of the airway and subglottic space. There was fibrous scarring outside the graft but no evidence of airway narrowing. Despite submucosal fibrosis, the mucosa appeared normal. The data documented that dogs tolerate subtotal cricoid resection very well and develop no subglottic stenosis. The resultant defect in the cricoid cartilage can readily be reconstructed with a PTFE graft. PMID- 1943111 TI - Frequency and experience with carcinoma of the thyroid at a private, a Veterans Administration, and a university hospital. AB - We evaluated the treatment experiences with thyroid carcinoma at a private, a Veterans Administration, and a University hospital to determine the frequency, treatment, and outcome of patients with this uncommon malignant tumor. All 120 patients with thyroid carcinoma were identified through hospital tumor registries between 1953 and 1988, representing 0.3% of the total cancer registry cases during this period. Well-differentiated carcinoma of the thyroid represented 73%, medullary carcinoma 7%, poorly differentiated carcinoma 18%, and Hurthle cell carcinoma 2% of histologic varieties. Seventy-eight percent of patients were treated initially by surgery or by surgery plus postoperative irradiation. The remaining patients received other treatment. At 10 years after treatment, 90% of patients with well-differentiated carcinoma survived, while only 20% of patients with medullary and poorly differentiated carcinoma survived. Sixty percent of recurrences for all histologic types appeared within the first 12 months after treatment. Patients with well-differentiated carcinoma had sporadic recurrences over a 21-year-period. Recognition of these time intervals allows for better follow-up management. PMID- 1943113 TI - Heating efficiency of radiofrequency capacitive hyperthermia for treatment of deep-seated tumors in the peritoneal cavity. AB - We analyzed heating profiles from 318 hyperthermic treatments of 39 patients with recurrent or inoperable cancers of the digestive organs whose deep-seated tumors were treated by radiofrequency (RF) capacitive heating of the abdominal region, and we investigated the heating efficiency and antitumor effect of such treatment. It was apparent that heating with a mean maximum RF output of 1,000 watts (700 watts at least), repeated four times or more, was necessary for a high rate of response by the tumor. Although it was difficult to heat tumors of the bile duct/pancreas to 42 degrees C or more, there was a strong positive correlation between maximum output of RF energy and maximum temperature of tumors (r = 0.839, P less than 0.001). The antitumor effect of RF hyperthermia was augmented with increasing output of RF energy. Therefore, the maximum level of RF output may be a useful index for expressing the heating efficiency with respect to intra-abdominal deep-seated tumors. PMID- 1943114 TI - Rhabdomyosarcoma of the bladder and prostate in children. AB - Fifteen children, 14 males and 1 female with a mean age of 4.9 years, were treated for rhabdomyosarcoma of the bladder and the prostate, between 1976 and 1985. In 14 patients, the disease was limited to the pelvis, while one had pulmonary metastases. The lesions were trigonal in 12 patients and involved the prostate in the other three. Eleven patients received vincristine-Adriamycin cyclophosphamide (VAC) chemotherapy, followed by radiation therapy. Four of these 11 patients required cystoprostatectomy for residual or persistent disease. Of the remaining four patients, two underwent radical cystoprostatectomy, one partial cystectomy and the patient with pulmonary metastases received only chemotherapy. Six patients were alive at 5 years (40% 5-year survival). Six patients died of local relapse within 18 months, one patient died of an unknown cause, while two patients were lost to follow-up free of disease after 2 years. PMID- 1943119 TI - Correlation between pathological risk factors and pelvic lymph node metastases in stage I squamous carcinoma of the cervix: a multivariate analysis of 194 cases. AB - This study includes 194 patients with stage I cervical cancer subjected to surgical therapy. Of 14 pathological factors analyzed, microscopic parametrial involvement (P = 0.001), depth of invasion (P = 0.001), and lymphovascular space invasion (P = 0.029) were found to be the most significant factors for positive pelvic lymph nodes. Combination of significant factors permitted categorization of patients into risk groups with pelvic lymph node metastases ranging from 0.0% to 90.9%. PMID- 1943117 TI - Treatment of metastatic malignant melanoma with 24 hours continuous venous infusion of dacarbazine and cisplatin. AB - Twenty consecutive patients with metastatic malignant melanoma were treated with a combination of 24 hours continuous infusion of dacarbazine (250 mg/m2) and cisplatin (20 mg/m2) for 5 days every 3 weeks. One patient (5%) achieved a complete response (CR) and 3 patients (15%) obtained a partial response (PR) with an overall response rate of 20%. Minimal response was observed in 5 other patients (25%). Complete response duration was 8 months. Median response duration of partial responders was 7 months. Median survival of all responders (CR+PR) was 8.5 months. Toxicity was mild to moderate. PMID- 1943118 TI - Clinical features of the differentiated and undifferentiated types of advanced gastric carcinoma: univariate and multivariate analyses. AB - This study was done to define clinical features for the different pathological types of advanced gastric carcinoma. One thousand one hundred three patients were identified and classified into two groups: 479 patients (43.4%) had a differentiated adenocarcinoma and 624 patients (56.6%) had an undifferentiated adenocarcinoma. Patients with the undifferentiated type were more likely to have large invasive tumors and a higher incidence of peritoneal dissemination. Conversely, the patients with the differentiated type were more likely to have a liver metastasis. Multivariate analysis, using Cox' proportional hazard model adjusted for sex, age, and other factors, suggested that tumor size was one of the seven most independent prognostic factors in patients with the undifferentiated type (relative risk = 1.01), but this parameter lost prognostic value in patients with the differentiated type. With regard to correlation between survival time and tumor size, the larger the tumor (over 10 cm), the shorter the survival time of patients with the undifferentiated type, as compared to findings in patients with the differentiated type (P less than 0.01). Thus, differences in clinical characteristics, including characteristics in the individual patients, extent of tumor, distant metastasis, prognostic factors, and prognosis correlate with the histopathological type of gastric carcinoma. PMID- 1943115 TI - Receptors for epidermal growth factor and steroid hormones in primary colorectal tumors. AB - The presence of epidermal growth factor, estrogen, and progesterone receptors (EGFR, ER, and PR) was investigated by a competitive binding assay in 43 colorectal adenocarcinomas and 32 normal colorectal mucosa specimens. EGFR were expressed in most of the tumor specimens analyzed at levels comparable with normal mucosa. There was no correlation between EGFR and tumor localization, tumor size, tumor stage, and grading. Among tumor specimens, 13.9% and 6.9% expressed very low but detectable ER and PR levels, respectively. No statistically significant difference was found between steroid hormone receptor levels in the tumor and normal mucosa specimens, and neither was there any correlation of ER and PR with the pathological findings. Our results suggest that the EGFR system may play a role in regulating the growth of colorectal tissues. Further studies should demonstrate whether, despite the lack of correlation with histopathological parameters, EGFR expression may have a biological significance in human colorectal cancer. PMID- 1943123 TI - Time course of spontaneous ventricular arrhythmias following acute coronary occlusion in the dog. AB - In this study, the arrhythmias occurring in dogs between 4 and 15 hr after occlusion of the left anterior descending coronary artery were continuously monitored by recording the electrocardiogram from bipolar leads. At 4.5 hr the number of dogs with less than 50% of sinus beats had increased and at 5 hr 15 min sinus beats represented on average 80% of total heart beats. In the period up to 6 hr isolated ventricular beats and ventricular salvos were seen in 95% and 63% of the dogs respectively and at 7 hr there were, on average, 50% of sinus beats and monomorphic ventricular rhythm was observed in 58% of the dogs. From 7 hr half the dogs had over 50% of ventricular ectopic beats and by 9 hr ventricular rhythm disturbances were permanently present in all the dogs. The ventricular arrhythmias reached a peak at about 11-12 hr (mean % sinus beats less than 10) when all dogs had a predominantly monomorphic (42%) and/or polymorphic (63%) ventricular heart rhythm. The characteristic time course of these cardiac disturbances suggest that it may form the basis for an experimental model that may be useful in analyzing the effects of potential antiarrhythmic drugs. PMID- 1943121 TI - The recording of action potential currents as an assessment for drug actions on excitable cells. AB - The use of the cell-attached patch clamp configuration to record action potential currents is shown to have utility in the testing for drug actions on ion channels in excitable cell membrane. A patch pipette was used to isolate a small patch of cell membrane on cultured hippocampal or hypothalamic neurons and spontaneous R-C coupled action potential currents, with well-defined Na+ and K+ components, were recorded. The addition of several potassium channel-blocking drugs to the bath solution completely abolished the after-hyperpolarization phase of the action potential currents while preserving the sodium spike. These drugs have previously been shown to block a calcium-dependent potassium channel in cultured hippocampal neurons, a channel that is responsible for the late slow after-hyperpolarization macroscopic current recorded in these cells. The addition of tetrodotoxin to the bath solution eliminated the R-C coupled currents. The novel approach of using the recording of action potential currents to assess drug actions on ion channels would be expected to be applicable to a variety of excitable cells. PMID- 1943122 TI - Evaluation of a microassay for human kininogens as cysteine protease inhibitors. AB - Several methods have been described for the identification and quantification of kininogens based on both immunochemical and functional characteristics. This article presents a rapid, cheap and simple microplate assay of kininogens based on their ability to inhibit cysteine proteases. The target enzyme papain is activated by cysteine HCl and the activated enzyme will be inhibited by added kininogens. The residual enzyme activity that is not inhibited in this reaction subsequently hydrolyzes the added substrate, S-2302, generating a yellow color that is read in a microplate reader at 405 nm. This method is very sensitive, the smallest amount of kininogen that causes significant inhibition of papain is established to be 0.01 micrograms. As a quantitative method, the assay performs accurately when approximately 0.1 micrograms of low molecular weight kininogen or high molecular weight kininogen is added to the test system. The within-run coefficient of variation (%) of the method was 1.7% when the inhibition of papain was in the range 45-70% and the day to day variation as low as 2.3% when performed with a papain inhibition of 80%. Applications of the method are presented, studying chromatographic separated kininogens in plasma, ascites, and urine. PMID- 1943120 TI - Chemo-irradiation induced aortoesophageal fistula. AB - A patient with squamous cell carcinoma of the esophagus developed fatal aortoesophageal (AE) fistula following a preoperative course of combined chemotherapy plus radiation therapy. This is the first reported case of AE fistula following preoperative chemoradiotherapy. This complication is potentially correctable if suspected early, since the massive hemorrhage characteristic of AE fistula is usually preceded by an initial sentinel hemorrhage. The cause of this complication is not clear, but it may be due to inflammation of the vasa vasorum with necrosis of the aortic wall. The concomitant use of fluorouracil and cisplatin with radiation therapy acts as a radiosensitizer and may have potentiated the radiation effect on the aortic wall. PMID- 1943128 TI - Theoretical considerations of the Tsou plot. AB - A graphical method was proposed by Tsou in 1962 for interpreting the data obtained by chemical modification of proteins and determining the number of essential groups involved. A strict mathematical proof and the estimation of deviation probability for this method are presented here. From the well-known Chebyshev's inequality, it has been shown that the possible error which could be derived from the Tsou plot will be much smaller than the usual experimental error obtainable. Some problems related to experiment and to application of Tsou plot in oligomeric enzymes have been discussed. Some analysis of experimental data taken from the literature are presented. PMID- 1943125 TI - A revised rotarod procedure for measuring the effect of antinociceptive drugs on motor function in the rat. AB - Tests of putative antinociceptive agents that rely on a motor response of an experimental animal to a noxious stimulus will give false positive results, and may be unethical, if the agent compromises motor function. We report a procedure for measuring potential effects of antinociceptive agents on motor function in the trained rat, using an 80 mm diameter rotarod. Rats were selected for ability to exercise on the rotarod and trained to increasing speeds. In test trials, we measured the time that trained rats could stay on the rod, rotating at 25 rpm, with a cut off at 60 min. Morphine administration decreased rotarod performance significantly at doses of 5.0 mg/kg (P less than 0.05, n = 10) and 7.5 mg/kg (P less than 0.005, n = 10). We also assessed the response to a noxious thermal stimulus by measuring tail flick latency following tail immersion in water at 49 degrees C. A significant dose-dependent increase in tail flick latency was found for dosages of morphine between 2.5 mg/kg and 7.5 mg/kg (P less than 0.005, n = 10). Our rotarod procedure, which incorporates selection, training, and a 60 min trial, provides a sensitive and consistent means of assessing motor function. Our results, implying that morphine indeed compromises motor function in rats at doses at which it is antinociceptive, confirm the necessity for investigating the motor effects of any putative antinociceptive agent. PMID- 1943126 TI - Method for studying the in vivo accumulation of inorganic mercury in segments of the nephron in the kidneys of rats treated with mercuric chloride. AB - A method for studying the in vivo accumulation of inorganic mercury along the nephron of Sprague-Dawley rats pretreated with a radiolabelled 0.66 mumol/kg dose of mercuric chloride is described in this article. Forth-eight hr after rats received the radiolabelled dose of mercuric chloride intravenously the kidneys of the animals were perfused in situ with a collagenase solution in order to dissect and isolate various readily assessable segments of the nephron and collecting duct. Three different categories of tubular segments were isolated; proximal convoluted tubules, proximal straight tubules and combined segments of the distal nephron and collecting duct. A group of isolated tubular segments were measured in length, drawn up and placed in counting tubes, and placed in a gamma counter for the determination of the content of inorganic mercury that accumulated in them during the 48 hr subsequent to the administration of the dose of mercuric chloride. In a separate set of animals, the intrarenal distribution of inorganic mercury was determined 48 hr after the intravenous dose of mercuric chloride was administered. Inorganic mercury accumulated mainly in the renal cortex and outer stripe of the outer medulla. In addition, the concentration of inorganic mercury in the outer stripe of the outer medulla was twice that in the cortex. The findings obtained with the isolated tubular segments revealed that most of the accumulated inorganic mercury in the kidneys of the rats was in the proximal tubule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943116 TI - Clinical usefulness of chemosensitivity testing using the MTT assay. AB - The results of in vitro chemosensitivity testing using the MTT assay of tumor cells from 140 patients were analyzed with reference to the clinical antitumor effects of the chemotherapy. One hundred and twenty-four (88.6%) of 140 specimens were successfully tested by the method of Mosmann (J Immunol Methods 65:55-63, 1983) with some modifications. When the results of the assay were compared with the clinical effects of chemotherapy in 22 patients with remaining measurable tumor lesions, the overall prediction rate was 86.4% (19/22). Among 31 patients with stage III-V gastric and colorectal carcinomas without remaining measurable tumor lesions, the survival rate of nine patients treated with drugs shown to be effective in the assay was significantly (P less than 0.05) better than that of 22 patients treated with drugs shown to be ineffective. PMID- 1943130 TI - Tendency-distance models of social cohesion in animal groups. AB - Although it has been assumed that attraction and repulsion between social individuals constitute a basis for group cohesion, there has been no systematic study of the possible ways in which these tendencies might vary with inter individual distance (IID), or of associated implications for group structure. In this paper, a family of attraction/repulsion--distance functions is described. Computer simulation was used to examine the effects of each function on group cohesion, as reflected by mean values and variability in IID and group shape. Our results showed that: (a) all models led to stability in group structure, but differed significantly in terms of stable IID and group shape characteristics; (b) cohesion was best served by an upwardly convex behaviour--distance function in which maximum attraction equaled maximum repulsion (and the biological plausibility of this function is discussed); (c) group elongation and variability in mean IID were significantly positively correlated; (d) although dyads maintained an equilibrial separation distance, at which attraction balanced repulsion, in larger groups stable nearest neighbour distances were often less than the equilibrium distance; and (e) individuals needed to monitor and respond to only relatively few of their companions in order to avoid group fragmentation. PMID- 1943127 TI - On the relation between the instability of ESS in discrete dynamics and segregation distortion. AB - There is a simple correspondence between discrete dynamical systems associated with evolutionary game dynamics and general locus multiallele selection models with non-Mendelian segregation. When interpreted properly the payoff matrix has two components, a fitness matrix component and a segregation matrix component. The presence of segregation distortion which corresponds to a non-symmetric payoff matrix, is a source of instability. With non-symmetric payoff an ESS does not usually correspond to a stable equilibrium. It is always externally stable but does not necessarily have an internally stable equilibrium. PMID- 1943124 TI - Neuroblastoma cells for testing neuroprotective drug effects. AB - An attempt was made to use neuroblastoma cells for testing neuroprotective drug effects. To achieve cellular damage, cytotoxic hypoxia was induced in neuroblastoma cells after 10 days in culture by addition of sodium cyanide (1 mmol/L) to the culture medium and was terminated after 6 hr by replacing the cyanide-containing fresh nutrient medium. During this hypoxic period cells were additionally deprived of glucose. They were allowed to recover for another 7 days. Drugs were available to the cells from 30 min prior to hypoxia until 24 hr after hypoxia. Cell concentration of high-energy phosphates and culture protein content were determined as representatives for the posthypoxic development of cell damage, cell activity and viability. While barbiturates and phenytoin revealed neurotoxic effects when applied in doses higher than 300 mumol/L, chlorpromazine, dizocilpine, ketamine, ketazocine, naftidrofuryl, and flunarizine protected neuroblastoma cells against hypoxic damage. These results were comparable to those obtained from primary cultures of neurons under similar experimental conditions. In addition, they were in keeping with neuroprotective drug effects obtained from in vivo experiments. It is suggested that neuroblastoma cells are suitable for testing neuroprotective drug effects. PMID- 1943129 TI - Early evolution of MHC polymorphism. AB - There is unwarranted satisfaction with the view that MHC polymorphism evolved because there was a selective advantage in having a variety of MHC proteins to bind a variety of peptide subsets for presentation to T cells. While this may, in part, explain its maintainance, polymorphism may have evolved initially to reject foreign virus "grafts". The possession of similar membranes promotes aggregation between "like" cells, but it also promotes aggregation between the cells and viruses which retain membrane components of their previous host. The selection pressure afforded by hostile virus "grafts" would favour cells which developed polymorphic membrane components (since "like" will not aggregate with "not like"). This polymorphism would have evolved before the appearance of multicellular organisms. Thus, the evolution of modern immune systems would have been imposed upon pre-existing polymorphic systems. A path this evolution may have taken involves the development of mechanisms for intracellular distinction between self and not-self. PMID- 1943131 TI - A sequence related to the human gonadoliberin precursor near the N-termini of HIV and SIV gag polyproteins. AB - A highly conserved sequence near the N-terminus of all human (HIV) and simian (SIV) immunodeficiency virus gag polyproteins appears to be a precursor for a viral mimic of the amidated C-terminus of human gonadoliberin. The gag polyproteins are known to be myristylated; processing of the amidation site would yield myristylated 23-residue peptides whose C-terminal sequences mimic gonadoliberin and presumably behave as ligands for the gonadoliberin receptor. This paper describes the discovery of conserved gonadoliberin-precursor-related sequences in HIV and SIV gag polyproteins and in the p-17 core proteins derived from them. Arguments are presented that the conserved precursor structure requires post-translational processing to a peptide amide derivative which is a ligand for the gonadoliberin receptor. A model has been developed for entry of the viral genomic RNA into host cells through the gonadoliberin receptor and experiments are suggested to confirm or refute the model. This proposed mechanism for entry of HIV genomic RNA into host cells, if it proves to be substantially correct, suggests several new approaches to prevention and treatment of acquired immunodeficiency syndrome (AIDS). PMID- 1943132 TI - Determining rate constants for irreversible polymerization where the initial step and propagation steps have different rate constants: consideration of polyadenylate polymerase. AB - A new relationship is derived between the amount of monomer incorporated and the amount of initiated primer in an irreversible polymerization where the first step, initiation, has a rate constant differing from the elongation rate constants. It is valid for template directed and template independent polymerization. This relationship can be used in kinetic simulation. It suggests a simpler curve fitting technique to attain rate constants from a relatively small data set. Our analysis reveals some limitations of the model of irreversible polymerization; these limitations have not been obvious previously. For example, the initiation rate constant is not attainable from simple monomer incorporation data. Reliable rate constants can be obtained with minimal time course studies. PMID- 1943137 TI - Mathematical model of antiviral immune response. II. Parameters identification for acute viral hepatitis B. AB - Considering the mathematical model of antiviral immune response, we describe a method of fitting the model to the data characterizing acute viral hepatitis B. The corresponding procedure employs an idea of sequential parameter estimation to make the problem of fitting manageable. The underlying mechanisms responsible for the quantitative manifestations of the four basic phases of acute hepatitis B are used to select the model parameters. The identified model of acute hepatitis B is then tested with regard to the following situations: the effect of HBsAg-specific antibodies on HBV challenge; the vaccination and the resistance to challenge using live hepatitis B virus; the dose of viruses--the incubation time relationships. The sensitivity of the model with respect to parameters variations is then analysed. The developed model allows us to quantitatively simulate the basic features of the antiviral immune response during acute hepatitis B and some closely related phenomena. PMID- 1943134 TI - A note on the evolution of meiosis. PMID- 1943138 TI - A new method for the analysis of the dynamics of the molecular genetic control systems. II. Application of the method of generalized threshold models in the investigation of concrete genetic systems. AB - Mathematical models of the prokaryotic control systems of tryptophan biosynthesis (both normal and with cloned blocks) and arabinose catabolism have been built using the method of generalized threshold models. Kinetic curves for molecular components (mRNAs, proteins, metabolites) of the systems considered are obtained. It has been shown that the method of generalized threshold models gives a more detailed qualitative picture of the dynamics of the molecular genetic control systems in comparison with the heuristic method of threshold models. The qualitative analysis of the functioning of the following mechanisms of control of the tryptophan biosynthesis: (1) inhibition of the activity of anthranilate synthetase by tryptophan, (2) repression and (3) attenuation of transcription of the tryptophan operon on the basis of the mathematical model of the control system of the tryptophan biosynthesis demonstrates that feedback inhibition is the most operative of the considered mechanisms while repression allows the bacterium to economize intracellular resources. As regards the control system of the arabinose catabolism the results of modelling enable us to state the following. The induction by arabinose within a wide range of parameter values causes two subsystems (araBAD and transport operons) of the arabinose regulon with a low rate of arabinose utilization to pass into a stationary regime and one subsystem (araC operon) to pass into a stable periodical regime. A study of the system characterized by the effective utilization of arabinose has shown that under induction by arabinose stable oscillations with small amplitudes of the concentration of regulatory protein and oscillations with large amplitudes of the concentrations of arabinose-isomerase and transport protein may occur. The period of the oscillation depends on the mean lifetime of the "activator-DNA" complex and on the rate constant of arabinoseisomerase degradation. PMID- 1943136 TI - Antigenicity of mouse monoclonal antibodies. A study on the variable region of the heavy chain. AB - Mouse monoclonal antibodies (Mabs) against human tumour antigens are currently used in therapy, but up to 50% of the patients receiving treatment form anti-Mab antibodies thus reducing the efficiency of the treatment. One attempt to minimize the immunogenicity of the mouse Mabs is to "humanize" them by replacing the constant part of the molecule with the human equivalent by genetic engineering. However, this does not reduce the immunogenicity of the variable part of the antibody. Some variable regions may be expected to be less antigenic than others. We therefore compared consensus sequences for the 11 mouse VH families with the human VH sequences published so far. Theoretical antigenicity predictions (hydrophilicity, flexibility, surface accessibility and relative antigenicity) were made and two families; VH I(J558) and VH XI (CP5 B5-3) were predicted to be immunogenic by all four methods. One family, VH X (MRL-DNA4), was not predicted to be immunogenic by any of the four methods. The residues predicted to form antigenic epitopes in the two families VH II (Q52) and VH III (36-60) are predicted not to be exposed on the surface of the antibody molecule and may therefore not be immunogenic. PMID- 1943145 TI - Prime numbers and the amino acid code: analogy in coding properties. AB - Natural numbers are characterized as being odd or even, prime or non-prime. If the quaternary information units of (DNA or RNA) nucleotide bases are assigned as 0 (for A), 1 (C), 2 (U or T) and 3 (G), then a unique set of amino acid numbers can be obtained by comparing the properties of numbers and coding properties. These numbers are: 0 for "stop" signals, 1 for Trp, 2 for Ile and 3 for Met. For other codons, synonymous quartets follow exclusively the P1 number series (prime numbers of the form 4n + 1); doublets mostly follow the P3 series (primes with quaternary remainder 3). A "one-to-one correspondence" between these numbers and the genetic code is established by considering their combinatorial specificities. PMID- 1943143 TI - The isometric force exerted per myosin head in a muscle fibre is 8 pN. Consequence on the validity of the traditional concepts of force generation. PMID- 1943139 TI - Co-operation and defection: playing the field and the ESS. AB - If food is patchily dispersed, food clumps being very rich, but rare and hard to find, each individual in a foraging flock then faces an evident dilemma: whether to co-operate and participate in the search, thus enhancing the rate by which rich patches are discovered, or to defect and let others do the searching, thus avoiding any possible expenditures and risks involved in the search (but enjoying the abundant resources once a rich patch is discovered). This conflict (and its possible solution) is treated as an example in the analysis of the synergistic n player game presented in this paper. After deriving conditions for the existence of a mixed ESS in such games, the evolutionary stability of the mixed strategy against invasions by pure strategists, in particular against invasions by recognizable defectors, is analyzed. Whereas in any "degenerating" mixed-strategy model a recognizable defector can invade and spread, a "non-degenerating" model can sometimes yield a mixed ESS which is immune to such invasions. PMID- 1943135 TI - Mathematical model of antiviral immune response. I. Data analysis, generalized picture construction and parameters evaluation for hepatitis B. AB - The present approach to the mathematical modelling of infectious diseases is based upon the idea that specific immune mechanisms play a leading role in development, course, and outcome of infectious disease. The model describing the reaction of the immune system to infectious agent invasion is constructed on the bases of Burnet's clonal selection theory and the co-recognition principle. The mathematical model of antiviral immune response is formulated by a system of ten non-linear delay-differential equations. The delayed argument terms in the right hand part are used for the description of lymphocyte division, multiplication and differentiation processes into effector cells. The analysis of clinical and experimental data allows one to construct the generalized picture of the acute form of viral hepatitis B. The concept of the generalized picture includes a quantitative description of dynamics of the principal immunological, virological and clinical characteristics of the disease. Data of immunological experiments in vitro and experiments on animals are used to obtain estimates of permissible values of model parameters. This analysis forms the bases for the solution of the parameter identification problem for the mathematical model of antiviral immune response which will be the topic of the following paper (Marchuk et al., 1991, J. theor. Biol. 15). PMID- 1943140 TI - The rationalization of high enzyme concentration in metabolic pathways such as glycolysis. AB - The cellular concentration of enzymes of some major metabolic pathways, such as glycolysis, can approach millimolarity. This concentration of enzyme can catalyze in vitro rates which are 100-fold higher than maximum pathway flux. In an attempt to understand the need for such high enzyme concentration, an artificial metabolic pathway of five enzymes (apropos the central enzymes of glycolysis) has been modeled. Numerical methods were then used to determine the effect of enzyme concentration on: (1) the change in total free metabolite concentration as the pathway changes from low flux to high flux, (2) the time lag (transient time) in the rate of final product formation upon the transition from low flux to high flux. Both the changes in metabolite pool size and the transient time decreased with increased enzyme concentrations. When all enzymatic reactions were assigned Keq of unity, a concentration for each enzyme of 25 microM is sufficient to provide a transient time of 1 sec. When Keq different from unity are introduced, more enzyme is required to provide comparably short transient times. Under the latter condition, a pathway of sufficiently low transient time would require all the enzyme available in mammalian muscle. It is shown that there is little scope for further increases in either enzyme concentration or of catalytic efficiency of independent enzymes. Therefore, an alternative method of increasing efficiency is considered in which enzyme-bound metabolites can serve directly as substrates for subsequent enzymes in a metabolic pathway. PMID- 1943133 TI - Computer simulation of growth of anastomosing microvascular networks. AB - Stochastic growth of polygonal microvascular networks was simulated on computer by dichotomous terminal branching and bridging (anastomosing with an existing segment). The model was applied to describe microvascular growth into a rectangular plane from the sides when vessels bifurcate in a probabilistic manner. The angle of bifurcation was drawn from a normal distribution, the mean of which was varied between 40 degrees and 80 degrees. The resulting networks contained an average of 88-104 nodes of which 30-38% were due to bridging. Number of nodes, number of branches, number of vascular polygons and a fractal dimension representing the density of nodes were calculated for each simulated network. Capillary density increased when mean angle of bifurcation was increased between 40 degrees and 80 degrees. Distributions of normalized vessel lengths and polygon shapes were compared with those of a mesenteric vascular network. The distributions were not found to be significantly different (p less than 0.05) for most values of the mean angle of bifurcation, matching best for the mean bifurcation angle of 50 degrees. Vascular polygons had an average shape between pentagonal and hexagonal for the mesenteric network as well as for all values of the mean bifurcation angle used in this study. PMID- 1943146 TI - Quantitative genetic variation and developmental clocks. AB - It is well-known that most genetic variation affects quantitative traits, and natural or artificial selection can act to change quantitative features of organisms more rapidly than qualitative ones. Surprisingly, variability is not confined to outbred species, but also occurs in inbred mice at a much higher rate than expected from known mutation rates. The size and shape of organisms and their constituent parts are, at least in part, controlled by the number of cell divisions, and there is published evidence for the existence of developmental clocks, which may count cell divisions. A molecular model for a developmental clock was previously proposed. It depends on the DNA methylation of repeated sequences of DNA, where the methylation of each additional sequence is tied to DNA synthesis and therefore cell division. The number of repeats specifies the number of divisions which will occur before a signal is produced which can activate or inactivate one or more genes. It is known that crossing over occurs between sister chromatids, and where tandemly repeated sequences occur unequal exchange can generate a larger or smaller number of repeats. An example of this is seen in the well-known variability of "minisatellite" sequences in human DNA. Unequal sister chromatid exchange can occur in mitotic and meiotic cells in the germ line, and in the case of developmental clock sequences could generate variation in clock length which in turn would directly affect quantitative traits. These events can be regarded as a special case of molecular drive during evolution. PMID- 1943141 TI - A unified model for T cell antigen recognition and thymic selection of the T cell repertoire. AB - Positive selection of T cells during thymic differentiation predisposes mature T cells to recognize glycoproteins encoded by "self" alleles of the major histocompatibility complex (MHC) as "restricting elements" for antigen presentation. Yet, negative selection also occurs during thymic differentiation resulting in the clonal deletion of T cells reactive with "self" MHC glycoproteins. Thymic processes of positive and negative selection represent a paradox because the "altered self" view of T cell receptor (TcR) recognition indicates that the same type of TcR-MHC glycoprotein binding interaction mediates both positive and negative selection of the T cell repertoire. Most contemporary models of thymic selection attempt to explain these paradoxical observations by quantitative differences of affinity. That is, TcR interactions with MHC ligands that are of medium affinity lead to positive selection whereas those that are of high affinity lead to negative selection. The purpose of this manuscript is to provide an alternative model of thymic selection based on the efficacy (the ability of a ligand to catalyze receptor mediated biological activity) of TcR-MHC ligand interactions. The "efficacy" model predicts that among those thymocytes exhibiting affinity for self MHC ligands, some clones bind self MHC ligands without efficacy whereas others bind these ligands with efficacy. Immature T cells that bind MHC ligands without efficacy do not undergo TcR mediated activation and thereby escape clonal deletion. Instead, these T cells compete for growth--promoting sites on thymic antigen presenting cells (APC) based upon their clonotypic TcR affinity for self MHC ligands. These T cells experience positive thymic selection and eventually dominate a repertoire of mature T cells predisposed to exhibit non-efficacious binding to "self" MHC ligands. In contrast, immature T cells that exhibit efficacious binding to self MHC ligands are deleted from the T cell repertoire during thymic maturation. By this mechanism, the mature T cell repertoire is selected so that clonotypic T cells are predisposed to bind the very sites on MHC glycoproteins responsible for antigen presentation without risk of autoimmunity. Given the clonotypic diversity of the mature repertoire, complexes of foreign peptides and self MHC glycoproteins would be recognized by clones of the appropriate specificity as highly efficacious ligands. In summary, the "efficacy" model is entirely consistent with the "altered self" concept of T cell antigen recognition and readily accounts for both positive and negative selection of the T cell repertoire. PMID- 1943147 TI - Gene regulation under growth conditions. A model for the regulation of initiation of replication in Escherichia coli. AB - A stochastic model is presented to describe gene regulation during growth conditions (non-steady-state), with an emphasis on the distribution of gene activation times. A non-Poissonian distribution, with a smaller variability than in steady-state, is obtained when gene activation by the regulatory protein(s) occurs before the protein(s) reach their saturation concentration. The model is applied to the regulation of initiation of chromosomal replication in Escherichia coli. The rate of initiation is shown to depend linearly on the concentration of the initiator molecule, DnaA, in good agreement with recently published data. It is suggested that the variability of initiation times could be growth rate dependent, with slow growing cells being more synchronized than fast growing ones. PMID- 1943148 TI - Identification of insulin receptor systems: assessing the impact of model selection and measurement error on precision of parameter estimates using Monte Carlo study. AB - An extensive Monte Carlo study has been carried out in order to study the effect of measurement error on the precision of parameter estimates of an insulin binding system. Hypothetical radioimmunoassay experiments were generated for insulin binding to erythrocytes. The design of experiments followed strictly the protocol of real experiments. Randomly generated error was added to the synthetic data. The standard technique, a weighted non-linear regression analysis, was employed to re-estimate parameters of a model of two receptor sites and a model of negative co-operativity. As the original parameter values were known, the differences between original and estimated values was studied for (a) measurement error in the range from 0-17%, (b) random initial estimates and (c) error-free non-specific binding. In addition, analytical estimates of parameter precision were compared with the true between-experiment variation of parameter estimates. At the measurement error of 12%, a one site model is recommended to estimate the high affinity population of the two sites model. Plausible results can be expected in 90% of experiments, the between-experiment variation being approximately 30%. The model of two receptor sites gives approximately two thirds of plausible results. The high affinity population can be estimated with the between-experiment variation of 40%, the low affinity population is virtually unidentifiable with the between-experiment variation of approximately 100% and parameter estimates biased to higher values. Only half of the results obtained from the model of negative co-operativity are plausible, the variation in parameter estimates ranges from 90-150% and estimates are biased to higher values. At the level of 12% measurement error, random initial estimates do not significantly affect the estimation process, provided initial estimates are selected from a feasible range. At the same measurement error, the error-free non specific binding does not improve the results, indicating that the mean of six replicates may be taken as a reliable estimate of non-specific binding. The analytical estimates of the coefficient of variation systematically underestimates the true between-experiments coefficient of variation, the difference has been found to be about 50%. PMID- 1943153 TI - Four analogies between biological and cultural/linguistic evolution. AB - The intricate phenomena of biology on the one hand, and language and culture on the other, have inspired many writers to draw analogies between these two evolutionary systems. These analogies can be divided into four principal types: species/language, organism/concept, genes/culture, and cell/person. Here, it is argued that the last analogy--between cells and persons--is the most profound in several respects, and, more importantly, can be used to generate a number of empirical predictions. In the first half of the paper, the four analogies are each evaluated after briefly describing criteria for a good predictive analogy. In the second half of the paper, the cell/person analogy and predictions deriving from it are explored in detail. PMID- 1943150 TI - Proto-splice site model of intron origin. AB - It is proposed that nuclear pre-mRNA introns (classical introns) were first generated as by-products during the evolution of alternative splicing. They were formed whenever two splice sites within the coding sequence of ancestral genes were used at a frequency that removed the coding constraint from the intervening sequence. Once introns had evolved, it is suggested that they were spread by the splicing machinery which inserted them into proto or cryptic-splice sites of other genes by reverse splicing, so giving rise to genes that have introns yet are not alternatively spliced. It is argued that 5' and 3' splice sites evolved from common ancestral splice sites, referred to as proto-splice sites, that were bidirectional and had a core consensus sequence of C or A, A, G, R, which remains today as the immediate flanking sequence of most introns. The ancestral splicing machinery, although inefficient, would have been capable of generating vast mRNA diversity by splicing between proto-splice sites. Natural selection would be expected to have preserved mutations that increased the amounts of advantageously spliced mRNA. It is argued that this process drove the evolution of present 5' and 3' splice sites from a subset of proto-splice sites and also drove the evolution of a more efficient splicing machinery. The positions of most introns that evolved directly from the coding sequence would be expected to correlate with protein structure. PMID- 1943149 TI - Antigen processing and presentation: how can a foreign antigen be recognized in a sea of self proteins? AB - A mathematical model describing the time-dependent events of antigen processing and presentation is utilized to quantitatively analyze the importance of newly synthesized Ia molecules as well as Ia molecules internalized from the cell surface in the formation of Ia-antigen complexes, the T cell receptor ligand. It has recently been shown that antigen presenting cells are not selective for the proteins they process and present. Therefore, we also investigate the ability of macrophages and B cells to process and present antigen in the presence of competing proteins often present in the extracellular environment. A set of criteria is formulated based upon experimental data to determine the validity of two model variations. We draw two major conclusions from our simulations. First, we determine that macrophages and B cells can present between 1-3 Ia-antigen complexes micron-2 for antigen concentrations in the range of 4-7 microM while in the presence of approximately 0-10 microM competing proteins or peptides. Second, we find it likely that antigen presenting cells, both B cells and macrophages, need to internalize Ia molecules from the cell surface in order for a sufficient number of Ia-antigen complexes to be presented. Binding of antigen to newly synthesized Ia alone does not, given experimentally reported values for Ia synthesis, allow sufficient Ia-antigen complex formation. PMID- 1943151 TI - A mechanism for acute aluminium toxicity in fish. AB - Aluminium is acutely toxic to fish in acid waters. The gill is the principal target organ and death is due to a combination of ionoregulatory, osmoregulatory and respiratory dysfunction. The toxic mechanism has hitherto received little direct consideration and is unknown. In this paper the mechanism of acute aluminium toxicity is approached from a chemical perspective. Symptomatic evidence of toxicity is taken from the literature and combined with our own research to elucidate a biochemically sound model to describe a possible mechanism of acute aluminium toxicity in fish. The proposed model delineates the chemical conditions immediately adjacent to the gill surface and emphasizes their importance in aluminium's toxic mode of action. The mechanism is shown to be bipartite. Aluminium binding to functional groups both apically located at the gill surface and intracellularly located within lamellar epithelial cells disrupts the barrier properties of the gill epithelium. The concomitant iono- and osmoregulatory dysfunction results in accelerated cell necrosis, sloughing and death of the fish. The mechanism of epithelial cell death is proposed as a general mechanism of aluminium-induced accelerated cell death. PMID- 1943155 TI - Molecular modeling of phytochrome. AB - Molecular models of phytochrome were generated to gain insight into structure function relationships of this important, tetrapyrrole-containing plant protein. Molecular dynamics simulation of a 51-amino acid segment surrounding the chromophore attachment site in oat phytochrome (Cys-321) generated a folded structure. Cys-321 was located within this structure in a beta-turn at the entrance of a distinct pocket. When attached to this amino acid, a semicircular conformation of the Pr chromophore easily fit within the pocket, with the sidechain carboxyl groups in association with Arg and Lys residues in the peptide backbone. Models of Z and E isomers at the C-4 or C-15 double bonds were generated to produce potential conformations of the Pfr chromophore. Comparison of predicted reactivity of the tetrapyrrole, deduced from the models, with that described in the extensive literature on phytochrome clearly indicated that isomerization at C-4 is consistent with experimental data. Isomerization at C-4 caused the chromphore to move partially out of the pocket and brought the sidechain carboxyl groups and ring D to the surface of the polypeptide. This change in orientation is compatible with the observed interaction of Pfr with metal ions, which possibly is a component in the physiological activity of this protein. PMID- 1943152 TI - Electronic structure of DNA by DV-X alpha cluster calculations. I. d(GG).d(CC), d(CG)2, d(GC)2 A and B conformations. AB - The electronic structure of d(GG).d(CC), d(CG)2, d(GC)2 which are stacked base pairs in the DNA double helix, are elucidated for both A and B conformations in detail by DV-X alpha cluster calculations. These three DNA double helix fragments are constructed from the same bases, G and C, but the electronic structure of the fragments for A and B conformations differs from each other characteristically. In particular, the electronic states of the O2 and O3 in phosphates differ drastically from each other, and might play a crucial role as recognition sites in various reaction processes concerning DNA. These differences are caused by the delicate differences in the admixture of the orbital components and the intra- and inter-bases interactions. Contour maps of the wavefunction of the HOMO and LUMO are compared among the stacking isomers. PMID- 1943156 TI - A stochastic attractor participates in chymotrypsin catalysis. A new facet of enzyme catalysis. AB - The previously observed discrete levels of vibrational parameters of chymotrypsin and tosyl-chymotrypsin were analyzed by the methods of non-linear dynamics in order to investigate their origin. The fractal dimensionality of the step sequence was determined using the correlation function and the Farey-tree method. These methods yielded the same value and indicated the presence of a "Devil's Staircase", i.e. the existence of a stochastic attractor. The latter was assigned to the substrate-mobilizable conformation. The attractor dimension of the catalytic site in the acylated state was found to be indistinguishable from that of the substrate mobilizable conformation. A "Devil's Staircase" signals the transition from the regular to the stochastic regime. This transition is shared by critical phenomena and may be a prerequisite for catalysis. PMID- 1943154 TI - Biochemical systems theory: operational differences among variant representations and their significance. AB - An appropriate language or formalism for the analysis of complex biochemical systems has been sought for several decades. The necessity for such a formalism results from the large number of interacting components in biochemical systems and the complex non-linear character of these interactions. The Power-Law Formalism, an example of such a language, underlies several recent attempts to develop an understanding of integrated biochemical systems. It is the simplest representation of integrated biochemical systems that has been shown to be consistent with well-known growth laws and allometric relationships--the most regular, quantitative features that have been observed among the systemic variables of complex biochemical systems. The Power-Law Formalism provides the basis for Biochemical Systems Theory, which includes several different strategies of representation. Among these, the synergistic-system (S-system) representation is the most useful, as judged by a variety of objective criteria. This paper first describes the predominant features of the S-system representation. It then presents detailed comparisons between the S-system representation and other variants within Biochemical Systems Theory. These comparisons are made on the basis of objective criteria that characterize the efficiency, power, clarity and scope of each representation. Two of the variants within Biochemical Systems Theory are intimately related to other approaches for analyzing biochemical systems, namely Metabolic Control Theory and Flux-Oriented Theory. It is hoped that the comparisons presented here will result in a deeper understanding of the relationships among these variants. Finally, some recent developments are described that demonstrate the potential for further growth of Biochemical Systems Theory and the underlying Power-Law Formalism on which it is based. PMID- 1943144 TI - Periodicity in DNA coding sequences: implications in gene evolution. AB - In this paper we have employed Fourier analysis of DNA coding and non-coding sequences in an attempt to identify possible patterns in gene sequences. It was found that while intronic sequences show a rather random pattern, coding sequences show periodicities and in particular a periodicity of 3. We were able to reconstruct such patterns by assuming a gene having one codon occurring in about 40% of the sequence. This could indicate that the predominant presence of codons all starting from the same base could confer the observed periodicities. Indeed, it was found that proteins do obey this rule. Implications of this finding in gene evolution are discussed. PMID- 1943142 TI - Kinetic parameters of enzymatic reactions in states of maximal activity; an evolutionary approach. AB - A theoretical investigation is presented which allows the calculation of states of maximal reaction rates for single enzymes and for unbranched enzymatic chains. As an extension to previous papers (Heinrich & Holzhutter, 1985, Biomed. biochim. Acta 44, 959-969; Heinrich et al., 1987, Bull. math. Biol. 49, 539-595) a detailed enzymatic mechanism was taken into consideration. Conclusions are drawn for the optimal values of the microscopic rate constants as well as of the maximal activities and Michaelis constants. Ten solutions are found which depend on the equilibrium constant as well as on the concentrations of substrates and products. It is shown that for high equilibrium constants one of the solutions applies to a very large range of the concentrations of the outer reactants. This solution is characterized by maximal values of the rate constants of all forward reactions and by non-maximal values of the rate constants of all backward reactions. In contrast to previous assumptions (Albery & Knowles, 1976b, Biochemistry 15, 5631-5640; Burbaum et al., 1989, Biochemistry 28, 9293-9305) states of maximal reaction rate are not always characterized by the highest possible values of the second-order rate constants which are related to the diffusion of the substrate and the product to the active site of the enzyme. Predictions are made concerning the ratios of maximal activities in optimal states as well as for the adaptation of the Michaelis constants to the concentrations of the outer reactants. Using metabolic control analysis it is shown that the solutions obtained for single enzymes may also be applied in multi enzyme systems. PMID- 1943157 TI - Ambrosia maritima: effects on molluscs and non-target organisms. AB - The actual knowledge about Ambrosia maritima is reviewed with emphasis on recent developments in the fields of plant morphology and taxonomy, the molluscicidal principles--the sesquiterpene lactones--present in the plant and the effects on snails and on non-target organisms. The use of the plant in traditional medicine is also discussed. Areas where more research is needed are outlined. PMID- 1943158 TI - Effect of Red Sea sponge extracts on blood glucose levels in normal mice. AB - The effects of extracts from 6 species of Red Sea sponges at two oral dose levels on blood glucose in normal mice were studied. Most extracts showed a hyperglycemic effect. An ethanol extract of Haliclona virdis showed a significant hypoglycemic effect lasting for more than 8 h after single oral doses of 200 or 500 mg/kg to normal mice. PMID- 1943159 TI - Systematic and medicinal reasoning in Mitla folk botany. AB - This paper reviews cognitive, symbolic, systematic botanical, and biochemical bases of plant classification, and analyzes their interrelationships in the medicinal folk botany of Mitla, Oaxaca, Mexico. It evaluates the "pharmacological wisdom" of the local population, along with their symbolic use of the environment, to show how they construct medicinal plant classifications which follow a folk logic, but often conform as well to modern botanical classifications based on the principles of systematic botany or chemistry. Working from both the chemical data and the folk categories, the analysis suggests the local Zapotec population systematically selected plants which foam for symbolic reasons to treat illnesses of the "soul" and identifies their underlying chemical constituents and medicinal qualities. Other correspondences between chemical, medicinal and reputed folk qualities are also suggested. PMID- 1943160 TI - Antiinflammatory activity of a Ghanaian antiarthritic herbal preparation: II. AB - A boiling water extract from a mixture of Alstonia boonei and Rauvolfia vomitoria root barks and Elaeis guineensis nuts without pericarp was tested for its antiinflammatory activity by measuring over a period of 17 days the changes in rat ankle diameter caused by subplantar injection of complete Freund's adjuvant. The extract fed in drinking water ad libitum reduced ipsilateral ankle adjuvant swelling by an average of 16% for the period of +4 to +17 days and improved weight gain. PMID- 1943161 TI - Direct relaxant effects of garlic juice on smooth and cardiac muscles. AB - The effects of garlic juice on smooth and cardiac muscles of rabbit and guinea pig were tested in vitro using isolated segments of aorta, trachea and intestines and isolated rabbit hearts. Garlic juice inhibited the contractions of rabbit and guinea pig aortic rings induced by norepinephrine in Ca(2+)-free and Ca(2+) containing Krebs-Henseleit solutions. Also, garlic juice inhibited the contractions of rabbit and guinea pig tracheal smooth muscles induced by acetylcholine and histamine, respectively, in both Ca(2+)-free and Ca(2+) containing Krebs-Henseleit solutions. Furthermore, garlic juice inhibited the spontaneous movements of rabbit jejunum and guinea pig ileum and inhibited the force of contraction of isolated rabbit hearts in a concentration-dependent manner. All inhibitions were reversible. These data suggest that the hypotensive action of garlic juice may be due, at least in part, to a direct relaxant effect on smooth muscles. PMID- 1943162 TI - Antiinflammatory evaluation of a Pluchea indica root extract. AB - A methanolic fraction of a chloroform extract of defatted Pluchea indica roots was investigated for its antiinflammatory potential against several models of inflammation. The extract showed significant inhibitory activity against carrageenin-, histamine-, serotonin-, hyaluronidase- and sodium urate-induced pedal inflammation. The extract inhibited protein exudation and leucocyte migration. The extract also inhibited carrageenin- and cotton pellet-induced granuloma formation as well as turpentine-induced joint oedema and adjuvant induced polyarthritis. The present observations establish the efficacy of the extract in the exudative, proliferative and chronic stages of inflammation. PMID- 1943163 TI - Plants used in traditional medicine in eastern Tanzania. V. Angiosperms (Passifloraceae to Sapindaceae). AB - Sixty-one Angiosperms (Passifloraceae to Sapindaceae) are listed, which are used by traditional healers in five regions of Eastern Tanzania, namely, Coast, Dar es Salaam, Kilimanjaro, Morogoro and Tanga. For each species listed, the botanical name, vernacular name, collection number, locality, habit, distribution and medicinal uses are given. Additionally, information from the literature on medicinal uses, chemical constituents and pharmacological effects are also provided. PMID- 1943164 TI - Inhibitory effect of peony root extract on pentylenetetrazol-induced EEG power spectrum changes and extracellular calcium concentration changes in rat cerebral cortex. AB - To elucidate the mechanism of anticonvulsant action of peony root and to determine the relative contributions of pure component substances, the water, water/acetone and methanol extracts of peony roots, paeoniflorin, albiflorin and pentagalloylglucose were studied in rats using the EEG power spectrum changes induced by pentylenetetrazol administration and the extracellular calcium and potassium concentration changes related to seizure activity. The water extract of peony roots, albiflorin and pentagalloylglucose given orally completely inhibited the EEG power spectrum changes as well as the extracellular calcium and potassium concentration changes related to seizure activity. The water/acetone and methanol extracts and paeoniflorin were relatively less potent. These findings suggested that the anticonvulsant action of peony roots is due primarily to albiflorin and the gallotannin fraction. Albiflorin and pentagalloylglucose appear to manifest their anticonvulsant action due to inhibition of the seizure-related decrease of extracellular calcium and consequent intracellular calcium increase. PMID- 1943165 TI - Repertory, therapeutic indications, chemical analysis and cultural background of mineral drugs of Afghanistan. AB - The traditional uses of minerals drugs and chemical products for medicine were studied in Afghanistan. Twelve medicinal drugs have been identified by chemical investigations and are presented in one table with the vernacular names (in Dari, Pasto and Kati); the origins and the therapeutical uses are listed in another table with their cultural background in pre-Islamic (Greek and Indian medicines) and Islamic pharmacopoeia (Afghano-Persian and Arabian medicines). Twenty-six other mineral drugs are also mentioned. PMID- 1943166 TI - [Pharmacologic effects of mansonine on arrhythmias induced in isolated rat heart]. AB - The effect of 3 x 10(-13) M Mansonine (MSN) was observed on arrythmias induced on isolated rat heart, perfused with either hypopotassic solution, atropine solution, or MacEwen physiological saline at 18 degrees C. Generally the reversal of induced arrythmias was complete with the hypopotassic solution, and partial with the MacEwen solution at 18 degrees C. On the other hand, when atropine and MSN were combined, their effects induced heart arrest, probably due to an intracellular calcium accumulation. In this case, the heart recovery occurred by preventing the calcium influx, either through EDTA chelation, or blockade of calcium channels. It was concluded that MSN probably acts like most cardiac glycosides, by blocking the Na(+)-K+ ATPase. This may activate a calcium influx, which causes the subsequent positive inotropic effect, as well as a negative chronotropic effect due to an increase of the membrane activation set point. PMID- 1943167 TI - The antimicrobial activity of the essential oil from Achillea fragrantissima. AB - Essential oil from Achillea fragrantissima exerted a bactericidic effect on several gram positive and gram negative bacterial strains, as well as on Candida albicans. The oil was fractionated on sillica gel columns by a gradient of ether in petrol ether (30 degrees C-40 degrees C). Two fractions which contained less polar compounds were active against C. albicans only. The fractions which contained more polar compounds inhibited the growth of all the microorganisms tested. One of these compounds was identified as terpinen-4-ol. Commercial terpinen-4-ol had a similar antimicrobial activity. PMID- 1943168 TI - Antipyretic activity of six indigenous medicinal plants of Tirumala Hills, Andhra Pradesh, India. PMID- 1943169 TI - Pharmacological screening of plant decoctions commonly used in Cuban folk medicine. AB - Pharmacological screening for cardiotonic, hypotensive or bronchodilator activities was performed on 50 plant species depending on their traditional medical use by the Cuban population. Eleven of these species may have promise as therapeutic agents, but additional preclinical pharmacological and toxicological studies are needed to establish their therapeutic effectiveness and safety in human disease. PMID- 1943170 TI - Anticholinergic action of Swertia japonica and an active constituent. AB - The anticholinergic action of Swertia japonica, used in Japan as a bitter stomachic, was examined using in vivo experiments in rats in order to substantiate the presence or absence of antispasmodic properties. The methanol extract of Swertia japonica was found to be an effective anticholinergic given orally. Fractionation and purification of the methanol extract through column chromatography revealed that swertiamarin, found in the methanol extract in amounts of about 30%, was an active constituent with an anticholinergic action. PMID- 1943171 TI - Probable mechanism of hypoglycemic activity of bassic acid, a natural product isolated from Bumelia sartorum. AB - Bassic acid, an unsaturated triterpene acid isolated from an ethanol extract of Bumelia sartorum rootbark, elicited significant hypoglycemic activity in alloxan diabetic rats and altered the pattern of glucose tolerance in these animals. In addition, bassic acid treatment increased significantly the glucose uptake process and glycogen synthesis in isolated rat diaphragm. Bassic acid treatment increased plasma insulin levels significantly in alloxan-diabetic rats. It is suggested that the hypoglycemia activity of bassic acid may be mediated through enhanced secretion of insulin from the pancreatic beta-cells. PMID- 1943172 TI - Ethnopharmacology of rhinoceros horn. II: Antipyretic effects of prescriptions containing rhinoceros horn or water buffalo horn. AB - Aqueous extracts of rhinoceros horn or water buffalo horn demonstrated significant antipyretic action at 2.5 g/ml i.p. (1 ml/animal) in rats with hyperthermia induced by subcutaneous injection of turpentine oil. Qingying Decoction, a classic compound prescription composed of rhinoceros horn and eight herbs, showed significant antipyretic action at dosages equivalent to 0.5 g/ml of rhinoceros horn extract. Comparable action was obtained by Qingying Decoction prepared with water buffalo horn. It is suggested that water buffalo horn can be used as a substitute for rhinoceros horn in treating hyperthermia, especially when prepared with other herbal materials according to the principles of compound prescriptions of Chinese medicine. PMID- 1943173 TI - Isolation and identification of the antibacterial compounds from Helichrysum stoechas. AB - Fractionation of the dicholoromethane extract of the aerial parts of Helichrysum stoechas yielded seven isolates (1-7), which exhibited varying antimicrobial activity against Gram-positive bacteria. Pure compounds 1-3 have been previously reported in the same species and 4 and 5 were identified as italipyrone and plicatipyrone, previously isolated from H. italicum and H. plicatum. The two other isolates are helipyrone (6) and homoarenol (7) mixed with related substances. Compound 6c (4,4'-dihydroxy-5,6,5',6'-tetramethyl-3,3'-methylen-di pyr-2-one) and 6b helipyrone with one methyl substitution, have not been previously reported in other species. PMID- 1943174 TI - Relaxant effect of the volatile oil of Rosmarinus officinalis on tracheal smooth muscle. AB - The effects of the volatile oil of Rosmarinus officinalis leaves on the tracheal smooth muscle of rabbit and guinea pig were tested in vitro using isolated tracheal strips. The volatile oil of R. officinalis leaves inhibited the contractions of rabbit tracheal smooth muscle induced by acetylcholine stimulation and the contractions of guinea pig tracheal smooth muscle induced by histamine stimulation. Also, the volatile oil inhibited the contractions of rabbit and guinea pig tracheal smooth muscle induced by high potassium (K+) solution. This inhibition was dose-dependent and reversible. Furthermore, the volatile oil inhibited the contractions of rabbit and guinea pig tracheal smooth muscle induced by acetylcholine and histamine stimulation, respectively, in Ca(2+)-free solution. These data suggest that the volatile oil of R. officinalis leaves has a calcium antagonistic property. PMID- 1943175 TI - Immunomodulatory activity of three Sri-Lankan medicinal plants used in hepatic disorders. AB - The effects of aqueous extracts of Osbeckia octandra whole plant, Melothria maderaspatana whole plant and Phyllanthus debelis leaves on the human immune system were investigated. The extracts showed strong anticomplement effects on both the classical and alternate pathways of the human complement system in vitro. The effects were dose-dependent and most pronounced in the classical complement pathway assay. The extracts also exhibited a direct dose-dependent inhibition of luminol-induced chemiluminescence of human polymorphonuclear leukocytes upon stimulation with zymosan. PMID- 1943176 TI - Effect of Salvia haematodes on sexual behaviour of male rats. AB - The effect of an ethanolic extract of Salvia haematodes roots was studied on the sexual behaviour of male rats. In the initial experiments, male sexual responses were assessed by recording penile erection, licking and grooming of genitals and copulatory movement in absence of females. In the second set, copulatory behaviour was observed by caging males with a receptive female brought into estrus with s.c. injection of estradiol benzoate and progesterone. The frequencies of mounting and intromission and latency of the ejaculation were recorded. The results show that the extract (500 mg/kg, orally) produced a significant increase in episodes of penile erection. The drug was found to enhance the orientation of males towards the female by increased anogenital investigatory behaviour and enhanced licking and grooming of the genitals. The extract also increased the ejaculation latency. These findings support the folk use of this plant as aphrodisiac and for the treatment of premature ejaculation. PMID- 1943177 TI - Neuropsychopharmacologic properties of a Schumanniophyton problematicum root extract. AB - Schumanniophyton problematicum is a plant popular among Nigerian native healers for the treatment of psychotic patients (madness). An extract obtained by ethanol extraction of the roots caused reductions in respiratory rate, body and limb tone, startle response and spontaneous locomotor activity after i.p. injection in mice, and was capable of inhibiting amphetamine-induced hyperactivity and stereotypic behaviour. It also induced passivity, piloerection, hypothermia and prolonged pentobarbital sleeping time. The i.p. LD50 of the extract in mice was 2.37 g/kg. The effects of the extract appear to be due to depression of central and autonomic system. PMID- 1943178 TI - Antimalarial activity of some plant remedies in use in Marracuene, southern Mozambique. AB - Two plants, Spirostachys africana and Bridelia cathartica, were selected for investigation on the basis of a clinical study of four herbal antimalarial remedies used in southern Mozambique. Petroleum ether, ethanol and aqueous extracts were tested for activity in vitro against Plasmodium falciparum. Crude ethanolic and aqueous extracts of the root and the ethanolic extract of the stem of B. cathartica caused a 50% inhibition of parasite growth at an incubation concentration of 0.05 microgram/ml. PMID- 1943179 TI - Sperm antimotility properties of a seed extract of Abrus precatorius. AB - This study examined the inhibitory effects of a methanol extract of Abrus precatorius seeds on the motility of washed human spermatozoa. The extract caused a concentration-related impairment of percentage sperm motility; with the EC50 concentration being 2.29 mg/ml. This effect on motility was essentially irreversible. With the highest concentration tested (20.0 mg/ml), the onset of the antimotility action was almost immediate. In addition, this concentration impaired the functional integrity of the plasma membrane (hypoosmotic swelling test) and viability (nigrosin-eosin stain) of spermatozoa. In contrast, with a lower concentration (5.0 mg/ml), such effects were not evident. It is concluded that at the lower concentrations the antimotility action may result from a rise in intracellular calcium (not via influx) and/or a decline in cAMP content and/or enhanced generation of a reactive oxygen species. PMID- 1943180 TI - Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. AB - The clinical efficacy of a herbomineral formulation containing roots of Withania somnifera, the stem of Boswellia serrata, rhizomes of Curcuma longa and a zinc complex (Articulin-F), was evaluated in a randomized, double-blind, placebo controlled, cross-over study in patients with osteoarthritis. After a one-month single blind run-in period, 42 patients with osteoarthritis were randomly allocated to receive either a drug treatment or a matching placebo for a period of three months. After a 15-day wash-out period the patients were transferred to the other treatment for a further period of three months. Clinical efficacy was evaluated every fortnight on the basis of severity of pain, morning stiffness, Ritchie articular index, joint score, disability score and grip strength. Other parameters like erythrocyte sedimentation rate and radiological examination were carried out on a monthly basis. Treatment with the herbomineral formulation produced a significant drop in severity of pain (P less than 0.001) and disability score (P less than 0.05). Radiological assessment, however, did not show any significant changes in both the groups. Side effects observed with this formulation did not necessitate withdrawal of treatment. PMID- 1943181 TI - Studies on the anti-ulcer activity of a Bryophyllum pinnatum leaf extract in experimental animals. AB - A methanolic fraction from an extract of Bryophyllum pinnatum leaves was found to possess significant anti-ulcer activity in nine different experimental animals models. Premedication tests in rats revealed that the extract possessed significant protective action against the gastric lesions induced by aspirin, indomethacin, serotonin, reserpine, stress and ethanol. Significant protection with extract treatment was observed to occur for aspirin-induced ulcer in pylorus ligated rats and for histamine-induced duodenal lesions in guinea pigs. Significant enhancement of the healing process was also found to occur in acetic acid-induced chronic gastric lesions in rats. PMID- 1943182 TI - Discovery in surgery: reflections on a golden age. PMID- 1943183 TI - Cardiac preservation in patients undergoing transplantation. A clinical trial comparing University of Wisconsin solution and Stanford solution. AB - Recent laboratory investigations have shown significantly improved donor heart preservation and function when the University of Wisconsin solution (UW) is used for arrest and storage. These findings prompted us to compare UW to Stanford solution in a clinical trial. After giving informed consent, patients were blindly randomized to receive a heart arrested and stored in UW or a heart arrested in Stanford solution and stored in normal saline. Orthotopic transplants were performed in a routine manner. Fourteen patients with a mean age of 54 years were randomized to UW, and 15 patients with a mean age of 51 years were randomized to Stanford solution. Mean donor ages (UW 27 years, Stanford 24 years) and ischemic times (UW 150 minutes, Stanford 135 minutes) were similar. Several differences were observed intraoperatively. At end ischemia, mean adenosine triphosphate (UW 5.87 mmol/gm wet weight, Stanford 4.75 mmol/gm) and creatine phosphate (UW 9.26 mmol/gm, Stanford 4.75 mmol/gm) levels were higher in the UW hearts (p less than 0.05). Defibrillation requirements (UW 14% [2/14], Stanford 53% [8/15]) were significantly less in the UW group (p = 0.05). The number of patients requiring temporary intraoperative pacing also showed a significant difference with 7% (1/14) of UW patients versus 47% (7/15) of Stanford patients requiring pacing (p less than 0.05). Intraoperative requirement for inotropic support showed a trend in favor of the UW group. End-ischemic and postreperfusion histologic characteristics were similar between the two groups. No differences in hemodynamics or ejection fractions were noted postoperatively, but trends toward improved rhythm and decreased inotropic support were present in the UW group. Overall 6-month survival rates were similar (UW 86% [12/14], Stanford 93% [14/15]). No preservation-related deaths occurred. We conclude: (1) UW is a safe and effective preservation solution for human cardiac transplantation; (2) considering the improved end-ischemic adenosine triphosphate and creatine phosphate levels, decreased defibrillations, decreased intraoperative pacing, and trend toward decreased requirement for inotropic support in the UW group, UW appears to be superior to Stanford solution for donor heart preservation. PMID- 1943184 TI - Prolonged hypothermic cardiac storage with University of Wisconsin solution. An assessment with human cell cultures. AB - Hypothermic storage of cardiac allografts is routinely used for transplantation but is associated with an increased mortality when ischemic times are greater than 4 hours. The ideal storage conditions (solution and temperature) could extend the current limits of cold ischemia. Human endothelial cells and ventricular myocytes were studied to screen various solutions and temperatures for organ preservation. Four solutions (modified Euro-Collins, phosphate-buffered saline, Stanford cardioplegia, and University of Wisconsin) were evaluated. Endothelial cells were evaluated after prolonged hypothermic storage consisting of 0 degree, 4 degrees, and 8 degrees C for 36 hours, and ventricular myocytes were stored at 0 degree and 8 degrees C for 24 hours. Cell viability was determined by morphology (10 dishes per group), and trypan blue exclusion (5 dishes per group) in addition to a cell adhesion assay (endothelial cells 5 dishes per group) and adenine nucleotide analysis with high-performance liquid chromatography techniques (ventricular myocytes 5 dishes per group). Endothelial cell morphology was best preserved by University of Wisconsin solution (p less than 0.001, chi 2) and at 0 degree C (p less than 0.01, chi 2). Endothelial cells stored with University of Wisconsin solution excluded trypan blue better (1.0% +/ 0.5% cells stained, p less than 0.001. Analysis of variance [ANOVA]). Cell adhesion was poorly protected with Stanford cardioplegia (p less than 0.001, ANOVA). Myocyte morphology was preserved best with University of Wisconsin solution at 0 degree C (p less than 0.001, chi 2). According to trypan blue staining, Euro-Collins and University of Wisconsin solutions were superior to Stanford cardioplegia or phosphate-buffered solutions (p less than 0.001, ANOVA). Temperature did not influence the trypan blue results. Adenosine triphosphate was maintained best with University of Wisconsin solution at 0 degree C (p less than 0.01, ANOVA). Myocytes were more sensitive to the effects of prolonged storage compared with endothelial cells by morphologic criteria and trypan blue staining characteristics, irrespective of the shorter preservation times. University of Wisconsin solution was the most effective solution tested. Colder temperatures (0 degree to 4 degrees C) provided better protection than 8 degrees C. Myocytes were more sensitive to prolonged preservation than endothelial cells. Furthermore, the technique used appears helpful as a model of prolonged hypothermic storage and could be expanded to assess other interventions. PMID- 1943185 TI - Temperature-response studies of the detrimental effects of multidose versus single-dose cardioplegic solution in the rabbit heart. AB - Both single-dose and multidose cardioplegia are protective in the ischemic adult heart under normothermic and hypothermic conditions, but in the hypothermic neonatal rabbit heart single-dose cardioplegia only is protective, whereas multidose cardioplegia is damaging. The present studies in the isolated perfused working heart from neonatal rabbits (aged 7 to 10 days) were designed to characterize the interrelationships between temperature, frequency of cardioplegic infusion, and tissue protection. Hearts (n = 8/group) were subjected to 1, 1.5, 1.5, 3, 10, 12, or 18 hours of ischemia at 37.0 degrees, 34.5 degrees, 32.0 degrees, 28.0 degrees, 20.0 degrees, 15.0 degrees, or 10.0 degrees C, respectively. These times were selected to achieve approximately 55% to 75% recovery of cardiac output in hearts during normothermic reperfusion when single dose (2 minutes) St. Thomas' Hospital cardioplegic solution was given at the onset of each ischemic period. Under these conditions actual recoveries of cardiac output were 55.7% +/- 5.6%, 68.5% +/- 6.8%, 73.8% +/- 4.1%, 54.6% +/- 5.3%, 56.3% +/- 7.5%, 59.5% +/- 7.7%, and 81.3% +/- 2.3% of the preischemic control values, respectively. By contrast, with multidose cardioplegia (given every 60 minutes in the 3- to 18-hour experiments and every 30 minutes in the 1- and 1.5-hour experiments) there was a temperature-dependent loss of protection when compared with single-dose cardioplegia; the recoveries of cardiac output were 75.7% +/- 1.5%, 78.4% +/- 4.8%, 65.0% +/- 5.8%, 36.7% +/- 5.8%, 34.6% +/- 7.5%, 25.9% +/- 6.0%, and 9.6% +/- 6.4%, respectively. These results were reflected in other indices of cardiac function and in changes in vascular resistance during cardioplegic infusion and reperfusion. To ascertain whether the progressive loss of protection was related to the degree of hypothermia or the duration of ischemia (which had to be increased as the temperature was lowered to permit a 55% to 75% recovery in the single-dose cardioplegia group), we conducted studies at a fixed temperature (20 degrees C) with variable durations of ischemia (6, 8, 10, and 12 hours). Finally, multidose and single-dose cardioplegia at 10.0 degrees, 20.0 degrees, and 37.0 degrees C were compared with hypothermia alone. We concluded that in the neonatal (in contrast to the adult) rabbit heart the protective properties of multidose cardioplegia relative to single-dose cardioplegia are progressively lost.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1943187 TI - Endothelial cell dysfunction after ischemic arrest and reperfusion: a possible mechanism of myocardial injury during reflow. AB - To determine the mechanism(s) responsible for decreased coronary flow after global cardiac ischemia and reperfusion, we studied 40 isolated rabbit hearts before and after 30 minutes of normothermic ischemic arrest and reperfusion. In the control group (n = 10) we evaluated the time course of recovery of coronary flow, vascular reactivity, and myocardial function. In experimental groups A (n = 10) and B (n = 10), metabolic control of autoregulation was assessed by plots of myocardial oxygen consumption versus coronary flow generated by incremental increases in heart rate. The slope and intercept of these plots suggested that autoregulation of coronary flow was maintained after ischemia. In group B hearts (n = 10) hyperosmolar reperfusion with mannitol decreased myocardial water by 2% (p less than 0.01) but did not increase coronary flow. Endothelium-dependent function was assessed in group C (n = 10) by the administration of an endothelium dependent vasodilator (serotonin) and a smooth muscle vasodilator (adenosine). Coronary artery smooth muscle function was comparable in hearts before and after ischemia. However, endothelium-dependent increases in coronary flow to serotonin were significantly impaired after ischemia (p less than 0.01), and this was accompanied by a significant decrease in prostacyclin synthesis by the endothelium (p less than 0.001). Global cardiac ischemia and reperfusion damages coronary artery endothelium, causing increased coronary vasomotor tone; this may be an important mechanism of decreased coronary perfusion and subsequent myocardial injury during reflow. PMID- 1943186 TI - Inconsistent effectiveness of myocardial preservation among cardiac chambers during hypothermic cardioplegia. AB - The purpose of this study was to examine the selective and differential natures of ischemic injuries among three cardiac chambers (right atrium, right ventricle, and left ventricle) from the viewpoint of ultrastructural morphometric study. Twenty consecutive adult patients undergoing cardiac operations were studied. The duration of aortic crossclamp time varied from 36 to 142 minutes (mean 83.4 +/- 36.4 minutes). Two serial specimens (preischemic and ischemic) were obtained from the right atrium, the right ventricle, and the left ventricle, respectively. A total of 120 biopsy specimens was obtained from these 20 patients. The average mitochondrial surface area of the left ventricle was 0.308 +/- 0.062 micron 2 in the preischemic stage and 0.352 +/- 0.083 microns 2 in the ischemic stage. This represented a 14.3% increase in mitochondrial surface area after ischemic injury (p less than 0.01). The mitochondrial surface area of the right ventricle showed an average increase of 43.7%, from 0.252 +/- 0.036 micron 2 in the preischemic stage to 0.362 +/- 0.087 micron 2 in the ischemic stage (p less than 0.0005). With respect to the mitochondrial surface area of the right atrium, there was an increase of 88.0%, from 0.217 +/- 0.044 micron 2 in the preischemic stage to 0.408 +/- 0.084 micron 2 (p less than 0.0005). The difference of mitochondrial swelling among three chambers was statistically significant (right atrium versus right ventricle versus left ventricle, p less than 0.0005). Moreover, the differences of mitochondrial swelling between any two chambers were also highly significant (right atrium versus right ventricle, p less than 0.0005; right ventricle versus left ventricle, p less than 0.01; right atrium versus left ventricle, p less than 0.0005). In conclusion, our findings suggest that from the viewpoint of ultrastructural morphometric study myocardial injury after an average of 83 minutes of ischemic arrest is poorer in the right chambers of the heart than in the left ventricle, with the right atrium having the poorest preservation. PMID- 1943188 TI - Oncogene activation in esophageal cancer. AB - We used molecular biology techniques to study the genetic events associated with the development of human esophageal cancer. Point mutations of the p53 tumor suppressor gene were detected in one of 10 squamous cell and one of 14 adenocarcinomas of the esophagus, a frequency that implicates this gene in tumorigenesis. However, the finding of p53 mutations in Barrett's epithelium adjacent to adenocarcinomas may have clinical implications for p53 as a premalignant marker for esophageal cancer. PMID- 1943189 TI - Anterior pericardial tracheoplasty for congenital tracheal stenosis. AB - Congenital tracheal stenosis may be a life-threatening anomaly not relieved by airway intubation. Over the past 7 years, anterior pericardial tracheoplasty has been used at our institution for treatment of congenital long-segment tracheal stenosis in infants with impeding airway obstruction. Case histories of eight patients undergoing nine anterior pericardial tracheoplasties have been reviewed to assess this technique. Of these patients, six have required preoperative tracheal intubation before repair to maintain ventilation. The surgical technique of anterior pericardial tracheoplasty includes a median sternotomy approach with partial normothermic cardiopulmonary bypass. An anterior tracheotomy through all hypoplastic rings allows enlargement with autologous pericardium to 1.5 times the predicted normal diameter. After insertion, the pericardium and hypoplastic tracheal cartilages are suspended to surrounding mediastinal structures, which prevents airway collapse. Seven of eight infants have survived without tracheoplasty dehiscence or wound infections. Five were ultimately extubated and are currently free of symptoms from 6 months to 5 years after anterior pericardial tracheoplasty. The other two survivors had residual stenosis as a result of complications of prior tracheostomy. One of these patients has undergone a successful second anterior pericardial tracheoplasty and is currently extubated and well. The other is palliated at 6 months with a tracheostomy awaiting a second anterior pericardial tracheoplasty. Our review of anterior pericardial tracheoplasty has demonstrated the safety, utility, and at least medium-term benefit of this procedure in infants of any age and weight. PMID- 1943190 TI - Surgical treatment of advanced thyroid carcinoma invading the trachea. AB - Operative methods, in relation to the completeness of resection and surgical results, and postoperative complications, in relation to operative methods, were discussed in 60 patients with advanced thyroid carcinoma in whom tumor invading the trachea was resected along with thyroid carcinoma. Laryngotracheal anastomosis was performed in 41 patients and tracheotracheal anastomosis in 19 patients. Complete resection was performed in 22 patients in the former group and in 12 patients in the latter group. Three-, 5-, and 10-year survival rates in patients undergoing complete resection were 87.0%, 78.1%, and 78.1%, respectively. Those for patients undergoing incomplete resection were 64.9%, 43.7%, and 24.3%, respectively. The locations of remaining tumor were the tracheal stump in patients in whom resection was incomplete. In four patients with esophageal invasion, the muscular layer of the esophagus was resected. Three of these patients had good postoperative results. Postoperative complications consisted of stenosis at the anastomosis in two patients, temporary mis swallowing in three patients, temporary lower pharyngeal stenosis in one patient, temporary vocal cord edema in one patient, and tetany in two patients. PMID- 1943191 TI - Expanded applications of diagnostic and therapeutic thoracoscopy. AB - From 1971 to 1990, 315 thoracoscopies were performed. Recent advances in optic/video systems and endoscopic operating instruments have made thoracoscopy easier and more accurate than 20 years ago. The operative mortality rate was low (1%) and the diagnostic accuracy high (99%). Thoracoscopy has been performed at an increasing frequency in recent years because of its expanded applications, especially in the areas of therapeutic or operative procedures such as carbon dioxide laser treatment of spontaneous pneumothorax or diffuse bullous emphysema, neodymium:yttrium-aluminum-garnet laser vaporization of pleural malignant tumors, and thoracoscope/laser-aided pleurectomy, pericardiectomy, or lung resection. Further technologic advancement in thoracoscopy will have a considerable impact on the future of thoracic surgery. PMID- 1943192 TI - Significance of changes in resting left ventricular ejection fraction after coronary artery bypass grafting. AB - The prognostic significance of changes in resting left ventricular ejection fraction was examined in 102 patients who underwent successful coronary artery bypass grafting. Between preoperative and early postoperative radionuclide ventriculography, mean resting left ventricular ejection fraction improved from 47.2% to 53.9% (p less than 0.01). Left ventricular ejection fraction increased by 5% or greater in 64 patients (63%), remained unchanged (within 4%) in 31 (30%), and decreased by at least 5% in 7 (7%). During 14 to 39 months (mean 27 months) of clinical follow-up, patients with normal preoperative left ventricular ejection fraction had a lower prevalence of recurrent angina, congestive heart failure, and mortality resulting from cardiovascular disease. Cardiovascular morbidity and mortality occurred with equal frequency for patients who did and did not show early postoperative improvement in left ventricular ejection fraction (36% versus 39%). Among 69 patients who had a third radionuclide ventriculography at late follow-up, left ventricular ejection fraction was less than the early postoperative value in 69% and less than the preoperative result in 36%. Patients with early postoperative improvement in left ventricular ejection fraction were more likely to retain resting left ventricular contractile function, at least at the preoperative level (71% versus 46%). PMID- 1943193 TI - Coronary artery bypass grafting within thirty days of acute myocardial infarction. Early and late results in 406 patients. AB - Between 1981 and 1987, 1726 coronary artery bypass operations were performed by a single group of surgeons at a community hospital. Overall hospital mortality in this group was 2.4% (41/1726). Of these patients 406 were operated on within 30 days of an acute myocardial infarction. The hospital mortality rate in this group was 6.7% (27/406) versus 1.1% (14/1320) in patients operated on without evidence of recent acute myocardial infarction (p less than 0.0001). In these 406 patients, sex, location of acute myocardial infarction, type of infarction, coronary anatomy, presence of postinfarction angina, technique of myocardial preservation, and the time from infarction to operation were not associated with hospital mortality. Univariate and multivariate analyses showed that three factors were significantly associated with increased hospital death: poor ejection fraction, less than 30% (p less than 0.0001), preoperative shock (p = 0.0005), and age greater than 70 years (p = 0.004). Follow-up was 90% complete (365/406 patients) at a mean time of 35 +/- 21 months. Of these patients 80% (292/365) were in New York Heart Association functional class I, and 10% (36/365) were in functional class II. Of all patients 88% were alive at 3 years, and 84% were alive at 5 years after operation. Multivariate comparison of survival curves showed that ejection fraction less than 30% was associated with decreased survival (p = 0.0002), followed by age (p = 0.0009). Patients younger than 70 years with an ejection fraction greater than 30% and not in cardiogenic shock can be operated on at any time after acute myocardial infarction without increased risk. Long-term survival and freedom from symptoms can be expected in these patients. PMID- 1943194 TI - Dissection of the two internal mammary arteries with maximal exposure and minimal adverse sequelae by means of an inexpensive, simple, atraumatic retractor. AB - The increasing use of internal mammary arteries for grafting, the possibility that both internal mammary arteries should be used, and the need for longer portions of these vessels should multiple sequential distal anastomoses be needed make a technique for safe and extensive dissection of these vessels important. We describe such a technique that uses a retractor adapter. This adaptation has considerably reduced our reluctance to use both mammary arteries and to dissect lengths that can be used for multiple distal anastomoses. It has also reduced the prevalence of undesirable side effects from retraction. PMID- 1943195 TI - Skeletal muscle extraaortic counterpulsation. A true arterial counterpulsation. AB - Reduction of left ventricular work load during systole, a critical component of arterial counterpulsation, has not previously been documented for skeletal muscle powered extraaortic counterpulsation. To assess its capacity for afterload reduction, a skeletal muscle extraaortic counterpulsator was connected to the thoracic aorta and counterpulsated. Canine hearts (n = 7) were instrumented with left ventricular Millar catheters (Millar Instruments, Inc., Houston, Tex.) for pressure measurements and with piezoelectric ultrasonic crystals for measurement of the left ventricular minor axis dimension and wall thickness. During systole, skeletal muscle extraaortic counterpulsation resulted in a significant change in all three determinants of left ventricular circumferential wall stress compared with control conditions (no counterpulsation). Pressure decreased (peak systole, 100 +/- 5 versus 75 +/- 6 mm Hg; p less than 0.05 by paired t test), minor axis dimension decreased (end systole, 46.4 +/- 1.1 versus 45.8 +/- 1.1 mm; p less than 0.05 by paired t test), and wall thickness increased (end systole, 10.4 +/- 0.7 versus 10.6 +/- 0.7 mm; p less than 0.05 by paired t test). Left ventricular wall stress/dimension work loops showed a shift downward and to the left, a shift consistent with afterload reduction. The mean systolic left ventricular wall stress was significantly reduced, from 67.3 +/- 10.6 to 47.7 +/- 8.1 10(3) dyne/cm2 (p less than 0.05 by paired t test). Skeletal muscle extraaortic counterpulsation increased the diastolic aortic pressure from 72 +/- 6 to 105 +/- 8 mm Hg (p less than 0.05 by paired t test). Our data, which documented the counterpulsator's direct effects on left ventricular functional mechanics, showed that skeletal muscle extraaortic counterpulsation is capable of both diastolic augmentation of arterial pressure and systolic unloading of the left ventricle. Skeletal muscle extraaortic counterpulsation has potential application for ventricular unloading in the treatment of chronic end-stage heart failure. PMID- 1943196 TI - Aortic counterpulsation for up to 28 days with autologous latissimus dorsi in sheep. AB - This article reports the development and assessment of an entirely autologous extraaortic counterpulsation system using skeletal muscle (latissimus dorsi). The technique has been performed and assessed in 16 sheep to quantify the effectiveness of counterpulsation over periods up to 28 days and to optimize the stimulation regimens for muscle contraction and fiber-type transformation. Hemodynamic changes have been quantified by calculation of the endocardial viability ratio. This has shown an increase of between 12% and 89% for 28 days. The wide variety of increase observed has been related to the development of an optimum flap configuration. The technique of surface impedance monitoring of flap blood flow has allowed the start of electrical stimulation after 48 hours with the introduction of hemodynamic benefit (1:4 mode) during the process of fiber type transformation (in situ training). Extraaortic counterpulsation with autologous latissimus dorsi has been shown to be effective and safe for as long as 28 days. It has not been associated with any thromboembolic or infective complications, which we attribute to the exclusion of any foreign material in the design. PMID- 1943197 TI - Preoperative prediction of postoperative pulmonary arteriolar resistance after surgical repair of complete atrioventricular canal defect. AB - The natural history of patients with complete atrioventricular canal defect is one of unrelenting development of pulmonary vascular obstructive disease. Corrective surgery, which can be performed with low mortality during infancy, reduces the time that the pulmonary vascular bed is exposed to excessively high pressure and blood flow. In some patients, however, advanced vascular disease may already be established at operation. Surgical intervention in these patients may not prevent the progression of obliterative pulmonary vascular disease and may in time even result in right ventricular failure, since after the corrective operation there is no ventricular septal defect to shunt away the right ventricular pressure overload. This article outlines a numeric method for predicting pulmonary vascular resistance after surgical correction; the method is based on age and hemodynamic data available from preoperative cardiac catheterization. Retrospective analysis of preoperative and postoperative data from 20 patients produced a regression equation in which a linear combination of inverse pulmonary/systemic blood flow ratio and age at operation predicted pulmonary vascular resistance after operation, with a multiple correlation coefficient of 0.85. This newly discovered relationship may provide valuable insight into the probable outcome of surgical intervention in cases in which pulmonary vascular obstructive disease is suspected as significant. PMID- 1943198 TI - A balloon-dilatable pulmonary artery band in the dog. Results at one year. AB - Increased pulmonary blood flow and pulmonary hypertension are frequent problems in infants with congenital heart disease. Although the use of pulmonary artery banding to limit pulmonary blood flow has decreased, the procedure may still be beneficial in certain forms of complex heart disease. The ability to noninvasively relieve the obstruction caused by the band may significantly reduce later operative complexity or even avoid reoperation entirely. The present study evaluated the effectiveness of a balloon-dilatable pulmonary artery band. Twenty 1-week-old dogs had a band of an absorbable suture material (Vicryl; Ethicon, Inc., Somerville, N.J.) placed around the main pulmonary artery. Eight dogs underwent angioplasty 6 months after band placement and also underwent follow-up catheterizations 3 and 6 months after angioplasty. Balloon angioplasty acutely reduced both the right ventricle-pulmonary artery pressure gradient (from 37 +/- 7 mm Hg to 3 +/- 1 mm Hg, p less than 0.001) and the right ventricular systolic pressure (from 62 +/- 8 mm Hg to 32 +/- 2 mm Hg, p less than 0.01). At follow-up the gradient remained low, measuring 4 +/- 1 mm Hg at 3 months and 3 +/- 1 mm Hg at 6 months. Twelve dogs did not undergo balloon dilatation until 12 months after band placement to determine whether any obstruction persisted and whether the band could be relieved after long-term placement. These 12 dogs had progressive increases in right ventricle-pulmonary artery gradient, from 27 +/- 3 mm Hg at 6 months to 43 +/- 4 mm Hg at 12 months. Ten of these dogs underwent dilation 1 year after pulmonary artery band placement. This dilation significantly reduced the right ventricular outflow tract gradient (from 43 +/- 4 mm Hg to 1 +/- 1 mm Hg, p less than 0.001). The remaining two dogs underwent successful partial dilation of the band 12 months after placement. This study demonstrated that a pulmonary artery band of absorbable suture material maintains effective right ventricular outflow tract obstruction for at least 1 year. Additionally, the effect of the pulmonary band can be successfully and persistently relieved. PMID- 1943199 TI - Clinical trial of University of Wisconsin solution for cardiac transplantation: preliminary results. PMID- 1943201 TI - Coronary artery bypass without extracorporeal circulation versus percutaneous transluminal coronary angioplasty: comparison of costs. PMID- 1943200 TI - Reply to invited letter concerning: Simulated left ventricular aneurysm and aneurysm repair in swine (J Thorac Cardiovasc Surg 1990;100:793-4) PMID- 1943202 TI - Benefit of heparin infusion through left ventricular catheter in patient undergoing mechanical valve replacement with the aid of a left ventricular assist device. PMID- 1943203 TI - Reparative cardiac operation in the preterm infant. PMID- 1943204 TI - Accurate sizing of aortic prostheses in the small aortic root. PMID- 1943205 TI - Another use for the mediastinoscope. PMID- 1943206 TI - Perforation of the right pulmonary artery branch to the right middle lobe with a Swan-Ganz catheter during cardiopulmonary bypass, resulting in endobronchial hemorrhage. PMID- 1943207 TI - In vitro translation in a hamster brain cell-free system. AB - We have developed a cell-free translation system derived from hamster brain tissue. The optimal incorporation conditions were 160 mM K+, 2 mM Mg2+ and microM spermine. The absence of this latter compound could be compensated only by doubling (to 4 mM) Mg2+ concentration. This system was inhibited by cycloheximide and emetine (elongation inhibitors) as well as NaF and aurintricarboxilic acid (ATA) (initiation inhibitors). The nature of the ATA inhibiting effect was studied by kinetic comparison with cycloheximide and polyribosome sedimentation pattern. PMID- 1943208 TI - A simple video position-digitizer for studying animal movement patterns. AB - A simple video position-digitizer has been developed for studying the movement patterns of small animals. This report provides a complete procedure for constructing the circuit, which when used in conjunction with a conventional video camera and an IBM PC compatible computer, automatically digitizes and records the path of a dark animal against a light colored background for relatively long periods of time. PMID- 1943209 TI - A low cost computer aided design (CAD) system for 3D-reconstruction from serial sections. AB - This paper describes an approach to computer-assisted 3D-reconstruction of neuronal specimens based on a low cost yet powerful software package for a personal computer (Atari ST). It provides an easy to handle (mouse driven) object editor to create 3D models of medium complexity (15,000 vertices) from sections or from scratch. The models may be displayed in various modes including stereo viewing and complex animation sequences. PMID- 1943210 TI - A method for the isolation of purified murine neuroepithelial cells from the developing mouse brain. AB - The adult mammalian central nervous system develops from the pseudostratified neuroepithelium of the neural tube. In order to study, in vitro, the differentiation of the neuroepithelial cells in detail and to identify factors that may influence this process, an uncontaminated, viable population of neuroepithelial cells, that still retains full developmental potential, is required. In this paper we describe a highly efficient method, involving differential trypsinization and micro-dissection, to cleanly separate the neuroepithelium from surrounding mesenchyme and ectoderm. The purity of isolated neuroepithelium has been assessed by monitoring for the presence of endothelial cells using an anti-endothelial antibody, MTS-12, and found to contain no significant level of contamination. Neuroepithelial cells prepared by this method have been demonstrated to divide and differentiate in tissue culture, to act as target cells for immortalization by proto-oncogenes and to differentiate into neurons in neural transplantation studies. PMID- 1943212 TI - Literature and medicine--tenth anniversary retrospective. PMID- 1943211 TI - A procedure for purifying low-abundance protein components from the brain cytoskeleton-nuclear matrix fraction. AB - We describe a preparative procedure for low-abundance proteins of the cytoskeleton-nuclear matrix fraction from frozen bovine brain. Strigent centrifugation and washing conditions in the preparation of the cytoskeleton nuclear matrix fraction are avoided to minimize loss of nuclear material. A recently described horizontal isoelectric focusing column, which tolerates appreciable precipitation, is used. In concert with selection of urea concentration and temperature, this isoelectric focusing apparatus provides a new approach to the fractionation of this complex, relatively insoluble mixture of proteins and other components. In addition, a heated, sodium dodecyl sulfate sizing column has been utilized in order to eliminate interactions between the desired low abundance proteins and more abundant contaminating proteins. Together these procedures purify a specific low-abundance protein sufficiently to be detected by Coomassie blue staining in two-dimensional gels. The methods are robust and can be applied to multiple, relatively large brain samples (150 g of crude grey matter per batch); thus they should facilitate partial peptide sequencing for brain proteins of this operational class. PMID- 1943213 TI - Toward the cultural interpretation of medicine. PMID- 1943214 TI - The word is an instrument of healing. PMID- 1943216 TI - Indexing the future. PMID- 1943215 TI - Pairing literature and medicine. PMID- 1943217 TI - Changing images of healers. PMID- 1943218 TI - An expostulation. PMID- 1943219 TI - Psychiatry and literature: a relational perspective. PMID- 1943220 TI - Toward a reciprocity of systems. PMID- 1943221 TI - A note on Billy Howard's photographs. PMID- 1943222 TI - Words and images in the time of AIDS. PMID- 1943223 TI - Victorian poets and physicians. PMID- 1943224 TI - Literature and bioethics: different approaches? PMID- 1943225 TI - Cloning of the t(11;14)(q13;q32) translocation breakpoints from two human leukemia cell lines. AB - The t(11;14)(q13;q32) translocation has been associated with several subtypes of human leukemia and lymphoma. It has been proposed that this translocation activates a proto-oncogene designated BCL1. In an effort to better understand the mechanism by which this translocation leads to malignancy, we have studied this translocation in two human cell lines. MO1094 and MO2058 were derived from patients with prolymphocytic variants of chronic lymphocytic leukemia. Southern blotting of the MO2058 cell line documented that the translocation linked the Jh region in the immunoglobulin heavy chain gene to the previously described BCL1 major translocation cluster (MTC). Using the polymerase chain reaction, we cloned this translocation and showed that the chromosome 11 breakpoint was within 7 bp of two other samples reported previously. Southern blotting of the MO1094 cell line suggested that the translocation in this cell line might link Jh sequences to a new region in the BCL1 locus on chromosome 11. Therefore, the MO1094 breakpoint was cloned from a genomic library. Comparison with normal cloned DNA from the BCL1 locus showed that the chromosome 11 breakpoint occurred 24 kb telomeric of the MTC. This work reinforces the concept that translocation breakpoints in the BCL1 locus are scattered over at least 63 kb. PMID- 1943226 TI - Near haploid acute lymphoblastic leukemia: seven new cases and a review of the literature. AB - Seven new cases are described of near haploid acute lymphoblastic leukemia (ALL) and the findings reviewed together with updated complete remission duration and survival data for the 21 cases already published. The patients were four males and three females, with an age range 2-19 years; all had an immunophenotype consistent with common ALL. The poor prognostic outlook for patients with near haploid ALL is confirmed by the median remission duration of 14 months for these patients, which is comparable to that for the previously published cases. The pattern of chromosome loss was marked particularly by the presence of two copies of chromosomes 10, 14, 18, 21 and both sex chromosomes. Populations of hyperdiploid cells with double the near haploid number were observed in six of the patients, one of whom demonstrated further clonal evolution, and it is proposed that some cases classified as hyperdiploid ALL with greater than 50 chromosomes may also have arisen from a near haploid stem line. PMID- 1943227 TI - Immunoglobulin and T-cell receptor gene rearrangements in acute non-lymphocytic leukemias. Analysis of 54 cases and a review of the literature. AB - Fifty-four unselected acute non-lymphocytic leukemias (ANLL) were analyzed for their immunophenotype, especially the expression of terminal deoxynucleotidyl transferase (TdT), as well as for rearrangements and/or deletions in the immunoglobulin heavy (IgH), Ig kappa, Ig lambda, T-cell receptor (TcR)-beta, TcR gamma and TcR-delta/alpha genes. In 15% (8/54) of the ANLL patients one or more genes were rearranged. This especially concerned IgH gene rearrangements (seven cases) and to a lesser extent rearrangements of Ig kappa genes (one case), TcR beta genes (three cases), TcR-gamma genes (two cases) and TcR-delta genes (two cases). Combined results from this study and from literature data on 378 unselected ANLL revealed that IgH gene rearrangements occurred in 14% of ANLL and Ig kappa gene rearrangements in 2% of ANLL patients. Rearrangements of Ig lambda genes have never been reported. Rearrangements of TcR-beta genes, TcR-gamma genes and TcR-delta genes have been found in 7, 5, and 9% of ANLL, respectively. In this study it was not possible to demonstrate an association between the presence of a TdT+ leukemic subpopulation and the occurrence of cross-lineage Ig or TcR gene rearrangements in ANLL. These rearrangements were detected in 13% (5/38) of ANLL with a TdT+ leukemic subpopulation and in 19% (3/16) of TdT- ANLL. Review of these data and over 400 published ANLL cases in which at least two different Ig and/or TcR genes had been investigated revealed that cross-lineage rearrangements of these genes concur frequently. Ig kappa gene rearrangements were only found in ANLL with rearranged IgH genes, whereas TcR-beta genes and TcR-gamma genes were only rearranged in combination with rearranged TcR-delta genes and/or IgH genes. Based on these data, an ordered pattern of cross-lineage Ig and TcR gene rearrangements in ANLL can be postulated, in which rearrangements of IgH genes or TcR-delta genes precede the other cross-lineage rearrangements. PMID- 1943228 TI - Clonal succession and deletion of bcr/abl sequences in chronic myelogenous leukemia with recurrent lymphoid blast crisis. AB - The development of cancer is generally believed to occur by a multistep process in which critical genetic defects accumulate in a clone of cells, confer a growth advantage, and result in the emergence of more malignant subclones. This paper describes the clonal origin of cells in a patient with Philadelphia-chromosome negative, M-bcr rearrangement-positive chronic myelogenous leukemia, observed in two episodes of lymphoid blast crisis (BC), the intervening chronic phases (CP), and following allogeneic bone marrow transplantation. Serial analysis of immunoglobulin heavy and kappa light chain (IgJH, IgCK), beta-T-cell receptor (beta-TcR) and bcr major breakpoint cluster region (M-bcr) gene rearrangements was performed. Clonal IgJH rearrangements present in cells of the first lymphoblastic crisis (BC1) were altered during the chronic phase post-treatment (CP1), and were again altered in recurrent blast crisis (BC2). In addition, the M bcr gene rearrangement present in BC1 and CP1 was absent from cells in BC2. These observations suggest that the course of clinical neoplastic disorders may not always be characterized simply by a hierarchical process of clonal evolution, but may also involve clonal succession of malignant cells. Moreover, the deletion of M-bcr in recurrent BC suggests that bcr/abl may not be essential for the maintenance of cell growth in established BC. PMID- 1943229 TI - Normal and neoplastic human plasma cells express bcl-2 antigen. AB - The bcl-2 (B-cell leukaemia/lymphoma 2) proto-oncogene is associated with the 14;18 translocation in follicular lymphoma juxtaposing bcl-2 with the immunoglobulin heavy chain region. bcl-2 has been cloned and sequenced and a monoclonal antibody to amino acids 41 to 54 of the bcl-2 protein has been raised. The expression of bcl-2 in follicular lymphoma has been demonstrated by immunohistological staining and also in normal lymphocytes. The presence of the bcl-2 onco-protein has been demonstrated by immunofluorescence using conventional and confocal microscopy in normal and malignant plasma cells from myeloma patients and myeloma cell lines. Plasma cells from 8/8 normal donors were positive, although the proportion of positive cells and the intensity of staining varied. Eight of 10 patients with myeloma or plasma cell leukaemia had positive plasma cells, and 6/11 plasma cell lines and one lymphoma cell line also expressed the onco-protein. bcl-2 expression is a feature of normal plasma cells and data from the cell lines confirm that expression is not dependent on the presence of the 14;18 translocation. PMID- 1943230 TI - Expression and regulation of IL-4 receptors on human monocytes and acute myeloblastic leukemic cells. AB - Evidence is presented that human monocytes and acute myeloblastic leukemic (AML) cells contain both high and low affinity binding sites for interleukin-4 (IL-4). On monocytes 183 +/- 132 high affinity binding sites per cell with a Kd of 60 +/- 29 pM and 1500 +/- 600 low affinity receptors with a Kd of 2.3 +/- 0.4 nM (X +/- S.D., n = 6) could be demonstrated. On AML cells (n = 11) a comparable number and binding affinity of IL-4 receptors were observed (77 +/- 36 high affinity receptors with Kd 72 +/- 31 pM and 2400 +/- 1000 low affinity receptors with Kd of 2.2 +/- 0.7 nM). In addition, no cross-competition was shown between radiolabeled IL-4 and IL-1-alpha, IL-3, IL-6, IL-7, G-CSF, and GM-CSF. Both types of receptors on monocytes as well as on leukemic blasts could be down-modulated in a similar fashion by IL-4 and activators of protein kinase C (PKC), but not by the calcium ionophore A23187. The down-modulation by PKC activators was caused by an increased internalization, degradation and release of radiolabeled IL-4 in the medium. Finally, the functionality of the IL-4 receptors were tested on AML cells with a 3H-thymidine proliferation assay. In 8/11 cases IL-4 affected AML proliferation. These data demonstrate two different binding sites for IL-4 on normal and leukemic cells, which can be modulated by external activation signals in an analogous way. PMID- 1943231 TI - Interferon gamma induces differentiation of cells from patients with myelodysplastic syndromes in vitro and in vivo. AB - A recombinant human interferon-gamma (IFN-gamma) was added to the clonal and suspension cultures of bone marrow (BM) cells from three patients with refractory anemia with excess of blasts (RAEB) before and after IFN-gamma therapy. IFN-gamma inhibited the hematopoietic progenitor cell growth from normal BM in one patient. In the remaining two patients with RAEB, IFN-gamma at lower concentrations (10 10(2) U/ml) consistently enhanced the growth of hematopoietic progenitors. The addition of IFN-gamma to suspension cultures promoted cellular differentiation in all three cases, as evidenced by persisting cytogenetic changes, Auer-rod containing maturing cells and cytochemical studies. Although IFN-gamma therapy resulted in partial or minor responses, these findings suggest the potential of IFN-gamma to act as an inducer of differentiation in myelodysplastic syndromes both in vitro and in vivo. PMID- 1943233 TI - Familial concordance in cancer. PMID- 1943232 TI - Models of childhood acute lymphoblastic leukaemia. PMID- 1943234 TI - Epidemiological clues to leukaemias involving specific chromosomal abnormalities. PMID- 1943235 TI - HPRT mutation frequency as an index of chemical or radiation damage. PMID- 1943236 TI - Cellular aspects of radiation-induced leukaemia. PMID- 1943237 TI - Naturally occurring radiation. PMID- 1943238 TI - Radon and leukaemia. PMID- 1943239 TI - Long memories are sometimes useful. PMID- 1943240 TI - Transesophageal echocardiography and cardiac masses. AB - Although transthoracic two-dimensional echocardiography has been a procedure of choice for diagnosing cardiac mass lesions, the advent of transesophageal echocardiography (TEE) provided better visualization of cardiac structures, especially those at a considerable depth from the chest wall, and lesions that involve the left atrial appendage. In this study, we examined the experience at our institution with TEE imaging of cardiac mass lesions (excluding valvular vegetations) from April 1988 to July 1990. TEE studies detected 83 lesions (in 80 patients), which we characterized by type and site: 46 left atrial, 16 right atrial, 7 left ventricular, 2 right ventricular, and 12 extracardiac mass lesions. Of the 46 left atrial lesions, 9 were tumors and 37 were thrombi that involved the body of the left atrium, the left atrial appendage, or both. Associated mitral valve disease, chronic atrial fibrillation, or spontaneous microcavitations were common. Of the 16 right atrial mass lesions, 4 were tumors and 12 were thrombi, including "string" thrombi characteristic of venous thromboembolism. Of the seven left ventricular mass lesions, six were thrombi and one was a papilloma. Of the 12 extracardiac mass lesions, 2 were pericardial cysts and the rest were solid lesions. TEE added new or important clinical information beyond that derived from transthoracic echocardiography in left atrial thrombi, right atrial masses, and extracardiac lesions and was assessed to have influenced the management of patients most in these areas also. TEE is a useful addition to transthoracic echocardiography for diagnosis and clarification of cardiac mass lesions in selected patients. PMID- 1943241 TI - Resection of select mediastinal parathyroid adenomas through an anterior mediastinotomy. AB - Two patients who had undergone thorough surgical exploration of the neck were found to have adenomas of fifth parathyroid glands within the mediastinum. After localization with computed tomographic scanning or thallium-technetium imaging, or both, these tumors were resected through a parasternal approach (anterior mediastinotomy); thus, median sternotomy was obviated. This approach has not been described previously for the removal of mediastinal parathyroid tumors. PMID- 1943242 TI - Predictive value of early electrophysiologic testing in determining long-term outcome with amiodarone treatment in patients with sustained ventricular tachycardia. AB - This prospective study sought to determine whether programmed ventricular stimulation before hospital dismissal in patients who had received a loading dose of amiodarone would identify those at risk for recurrent ventricular arrhythmias. Between January 1985 and January 1989, 64 patients (55 men and 9 women; mean age, 64 years) with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation were referred to our institution for electrophysiologic testing. Of these patients, 52 had coronary artery disease, 11 had dilated cardiomyopathy, and 1 had hypertrophic cardiomyopathy. Of the 64 patients, 47 had baseline tests while no drugs were administered and repeated electrophysiologic testing after 10 days of amiodarone loading (1.2 g/day). The other 17 patients had no baseline study because of instability of their arrhythmias but underwent electrophysiologic testing after amiodarone loading. Follow-up ranged from 7 to 1,536 days (mean, 652 days). During the follow-up period, recurrent arrhythmias were detected in 22 patients. Of the 64 patients, 14 had suppression of VT. Of 43 patients in whom the cycle lengths of VT were determined both at baseline and after amiodarone therapy, 20 had an increase of 100 ms or more, and 23 had no substantial change. The mean ejection fraction was 31%. Of a total of 16 deaths in the series, 8 were sudden. Suppression of VT during amiodarone therapy suggested a lower rate of fatal and nonfatal recurrent arrhythmias, but the difference was not statistically significant. An increase in the cycle length of VT did not predict an improved outcome. The age of the patient and the presence of a left ventricular aneurysm were slightly predictive of mortality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943243 TI - Quantitative blood cultures in candidemia. AB - The relationship between quantitative data on peripheral blood cultures and source of infection was studied in 172 episodes of candidemia that occurred in 169 patients. Clinically, the source of candidemia was an intravascular device in 67 episodes, an extravascular source in 73 episodes, and endocarditis in 2 patients; no source was identified for the other 30 episodes. Colony counts were determined in peripheral blood specimens on the first day of candidemia by the lysis-centrifugation system. High-grade and low-grade candidemia were defined as 25 colony-forming units or more per 10 ml and 10 colony-forming units or fewer per 10 ml of blood, respectively. Of 48 episodes of high-grade candidemia, 43 (90%) were associated with an infected intravascular device; therefore, the presence of high-grade candidemia should prompt the removal of intravascular devices. In contrast, 92 of the 112 episodes of low-grade candidemia (82%) had an extravascular or an unidentified source of candidemia. In patients with infections associated with an intravascular device, colony counts declined significantly within 72 hours after removal of the device in the absence of antifungal therapy; failure to decline suggests an alternative source of persistent infection. Quantitative data from peripheral blood cultures may help distinguish intravascular from extravascular sources of candidemia and aid in assessing the response to the removal of infected intravascular devices. PMID- 1943244 TI - Sleep and breathing in patients with the Prader-Willi syndrome. AB - The Prader-Willi syndrome is characterized by infantile hypotonia, early childhood obesity, mental deficiency, short stature, small hands and feet, and hypogonadism. Many patients also have hypersomnolence, experience daytime hypoventilation, and subsequently die prematurely of cardiorespiratory failure. Hypersomnolence and daytime hypoventilation are also common occurrences in the sleep apnea syndrome. For a better understanding of the relationship of sleep to the features of the Prader-Willi syndrome, we retrospectively reviewed five patients (two adults, one adolescent, and two children) with this syndrome who underwent polysomnography. All patients were obese; they had hypersomnolence and daytime hypoxemia, and they nored. In all patients, the apnea plus hypopnea index was less than 10 episodes per hour of sleep. During rapid eye movement sleep, nonapneic reductions in oxyhemoglobin saturation were detected in one adult and in one child. Despite the presence of morbid obesity and a history of snoring, patients with Prader-Willi syndrome seem to have only mild sleep-disordered breathing. PMID- 1943245 TI - A patient with pulseless extremities: an unusual manifestation of cardiac tamponade. AB - We describe a 51-year-old man who came to our institution with cold cyanotic extremities. He was receiving radiation therapy for adenocarcinoma of the lung and superior vena cava syndrome. Findings on initial physical examination were notable for absent peripheral pulses and increased jugular venous pulsations. Shortly after admission, the patient experienced severe dyspnea and tachypnea. Arterial blood gas studies revealed mild metabolic acidosis. A chest roentgenogram showed an enlarged cardiac silhouette and the known mass in the right upper lobe of the lung. An electrocardiogram demonstrated no evidence of ischemia but low-voltage QRS complexes. An emergency echocardiogram disclosed a large pericardial effusion and evidence of hemodynamic compromise. With use of echocardiographic-guided pericardiocentesis, 600 ml of bloody fluid was removed; the pulses were immediately palpable in the patient's extremities. Although symptoms associated with the extremities are unusual as the initial complaint of patients with cardiac tamponade, we illustrate several key physical findings and abnormal results of laboratory test characteristic of this disorder. In addition, we underscore the importance of considering this diagnosis, especially in patients with a malignant tumor, and we describe the prompt response to therapy. PMID- 1943246 TI - Loss of dental enamel in a patient taking cholestyramine. AB - During treatment with cholestyramine for high concentrations of cholesterol, extensive loss of dental enamel occurred in a young boy. This outcome is thought to be attributed to mixing the cholestyramine in Kool-Aid and swirling the mixture in the mouth before swallowing. PMID- 1943247 TI - Advances in gynecologic imaging and intervention. AB - Advances in diagnostic imaging of the female genital tract facilitate characterization of many pelvic masses. Preoperative assessment of gynecologic malignant tumors provides information that may alter the surgical approach or timing of radiation therapy. Image-guided biopsy accurately confirms recurrent malignant lesions. Transcervical techniques have improved diagnostic assessment of infertile couples; thus, effective and inexpensive treatment options can be offered. Postoperative complications of gynecologic procedures can be detected with imaging, and many can be treated with image-guided techniques. PMID- 1943248 TI - The monobactams. AB - The monobactam antibiotics are synthetic compounds, although monocyclic beta lactam compounds have been found in nature in various soil bacteria. Although additional orally and parenterally administered monobactams are under investigation, the first marketed monobactam was aztreonam. This agent has an antimicrobial spectrum similar to that of gentamicin and tobramycin, aminoglycoside antibiotics. Aztreonam, however, is not nephrotoxic, is weakly immunogenic, and has not been associated with disorders of coagulation. Aztreonam may be administered intramuscularly or intravenously; absorption after oral administration is poor. The primary route of elimination is the urine. The serum half-life of the drug in patients with normal renal function is 1.5 to 2.1 hours; the recommended dosing interval in patients with normal renal function is every 8 hours. Dosage adjustment is necessary in patients with renal impairment. The strictly gram-negative aerobic spectrum of aztreonam limits its use as a single empiric agent. Approved indications for its use include infections of the urinary tract or lower respiratory tract, intra-abdominal and gynecologic infections, septicemia, and cutaneous infections caused by susceptible organisms. Concurrent initial therapy with other antimicrobial agents is recommended before the causative organism (or organisms) has been determined in patients who are seriously ill and at risk for gram-positive or anaerobic infections. PMID- 1943249 TI - The aminoglycosides. AB - Despite the introduction of newer, less toxic antimicrobial agents, the aminoglycosides continue to serve a useful role in the treatment of serious enterococcal and gram-negative bacillary infections. Gentamicin, because of its low cost, remains the aminoglycoside of choice in hospitals with low levels of resistance among Enterobacteriaceae and Pseudomonas aeruginosa. Amikacin is useful against gentamicin-resistant gram-negative bacilli and also in the treatment of infections caused by susceptible Nocardia and nontuberculous mycobacteria. An alarming increase in resistance to aminoglycosides among enterococci has been noted, despite little change in susceptibility patterns among gram-negative bacilli. Future efforts will need to be directed toward a better understanding of mechanisms of antimicrobial resistance and toward the prevention of aminoglycoside-induced toxicity. PMID- 1943250 TI - Vancomycin. AB - Vancomycin is a glycopeptide antibiotic that is active against staphylococci, streptococci, and other gram-positive bacteria. It is the drug of choice for the treatment of infections due to methicillin-resistant staphylococci, Corynebacterium jeikeium, and multiply resistant strains of Streptococcus pneumoniae. Vancomycin is an alternative treatment for serious staphylococcal and streptococcal infections, including endocarditis, when allergy precludes the use of penicillins and cephalosporins. Vancomycin is bactericidal against most strains of staphylococci and nonenterococcal streptococci. Although rare strains of staphylococci and enterococci that are resistant to vancomycin have been reported, bacterial resistance has thus far not emerged as a major clinical problem despite widespread use of vancomycin. When therapy is monitored by periodic determinations of serum concentrations of the drug and rapid infusion rates are avoided, vancomycin is rarely associated with serious toxicity. PMID- 1943251 TI - Transesophageal echocardiography and cardiac masses. PMID- 1943252 TI - Advances in the operative management of persistent hyperparathyroidism. PMID- 1943253 TI - Hypoxemia in malignant carcinoid syndrome: a case attributed to occult lymphangitic metastatic involvement. PMID- 1943254 TI - Biomedical signal processing (in four parts). Part 3. The power spectrum and coherence function. AB - This is the third in a series of four tutorial papers on biomedical signal processing and concerns the estimation of the power spectrum (PS) and coherence function (CF) od biomedical data. The PS is introduced and its estimation by means of the discrete Fourier transform is considered in terms of the problem of resolution in the frequency domain. The periodogram is introduced and its variance, bias and the effects of windowing and smoothing are considered. The use of the autocovariance function as a stage in power spectral estimation is described and the effects of windows in the autocorrelation domain are compared with the related effects of windows in the original time domain. The concept of coherence is introduced and the many ways in which coherence functions might be estimated are considered. PMID- 1943255 TI - Use of discrete Hilbert transformation for automatic spike mapping: a methodological investigation. AB - On the basis of discrete Hilbert transform (DHT) realised by fast Fourier transform (FFT), a new strategy for automatic spike mapping is introduced. The further computation of the EEG time series after DHT results in the time series of the momentary power and the momentary frequency. Both are used for the solution of the main requirements of automatic spike mapping. The spike-mapping concept introduced meets the requirements of efficient automatic spike detection and also has an insensitivity with regard to EMG interference and transient signal components, a frequent cause of false positive detections. Additionally, there are advantages if the momentary power of the spike is mapped instead of the spike potential. The use of momentary power makes a combination of power spectral mapping and spike-mapping strategies possible. PMID- 1943256 TI - Using discrete Hilbert transformation for interval-related calculation of the respiration rate in neonates. AB - From the basis of the fast Fourier transformation (FFT), the discrete Hilbert transformation (DHT) is used to compute the instantaneous respiration rate in neonates. This interval-related computation of respiration rate must be combined with a concept of adaptive filtration of the respiratory movements. This strategy is performed by adaptive recursive estimations of mean values with different adaptation constants. Additionally, a frequency band limitation is carried out on the basis of the peak characteristic of the power spectrum (respiratory movements). By means of the adaptive estimation of the variance of respiratory movements, an amplitude-time window is calculated to choose between epochs with breaths and apnoea. PMID- 1943257 TI - Knowledge-based approach to the management of serious arrhythmia in the CCU. AB - An expert system (SETA) for the management of patients in the CCU environment has been developed. SETA suggests therapeutic actions for the treatment of serious arrhythmias that complicate the pathophysiological state of patients recovering from acute and suspected myocardial infarction. The prototype begins by reasoning from the arrhythmia, diagnosed from the ECG signal, and progresses through its inference process by considering ECG changes (i.e. heart rate, QRS width), patient clinical data, patient history and therapeutic drug data, to reach the most appropriate actions for each particular patient. The system was implemented on production rules using M1 as a development tool. SETA uses a multiknowledge base (KB) architecture, one for each particular arrhythmia and relevant complication, and a decision board that controls the firing of the KBs and keeps track of patient status through time. The system takes into consideration aspects that are very important for the human expert, e.g. sequence of arrhythmia appearance, drug contraindications and priority in the case of simultaneous arrhythmia. The development of this system has given insight into the management of critical CCU patients, that should influence the specification and design of intelligent instruments for this clinical environment. PMID- 1943258 TI - Stimulation of a myelinated nerve axon by electromagnetic induction. AB - A model of electromagnetic stimulation predicts the transmembrane potential distribution along a myelinated nerve axon and the volume of stimulated tissue within a limb. Threshold stimulus strength is shown to be inversely proportional to the square of the axon diameter. It is inversely proportional to pulse duration for short pulses and independent of pulse duration for long ones. These results are also predicted by dimensional analysis. Two dimensionless numbers, Sem, the ratio of the induced transmembrane potential to the axon's threshold potential, and Tc/T, the ratio of the pulse duration to the membrane time constant, summarise the dependence of threshold stimulus strength on pulse duration and axon diameter. PMID- 1943259 TI - Open-loop position control of the knee joint using electrical stimulation of the quadriceps and hamstrings. AB - The clinical acceptability of functional electrical stimulation (FES) as an aid for restoration of paraplegic gait is limited by the inability to accurately and repeatedly position the lower extremity. To gain insight into the causes of and possible solutions to this problem, the responses of the quadriceps and hamstrings to FES were studied in able-bodied subjects. Isometric torque was dependent on knee angle and changed unpredictably with time. An open-loop feedforward knee-joint position controller was also tested. The results demonstrated that it is beneficial to account for the dependence of torque on position, that modifications to this open-loop controller might improve accuracy and that closed-loop control may be essential for functional restoration of gait. PMID- 1943260 TI - Biphasic model of the trabecular meshwork in the eye. AB - A biphasic continuum model for the flow of intraocular fluid, the aqueous humour, in the trabecular meshwork is proposed in the paper. The model considers the meshwork as a circular ring with uniform thickness of homogeneous, isotropic, viscoelastic material swollen with continuously percolating aqueous humour. The model further assumes the permeability of the meshwork as a function of dilation in its solid phase. The study considers steady and quasisteady states. Approximate solutions to the problem are obtained by Picard's type iterative procedure and computational results for the dimensionless solid displacement, permeability and pressure profiles are presented. It is concluded that intraocular pressure has a permeability-decreasing effect, whereas the elasticity of the meshwork shows a permeability-increasing effect. Thus, rising intraocular pressure develops a further rise in itself, whereas the elasticity tends to diminish the intraocular pressure through facilitating aqueous outflow. PMID- 1943261 TI - Coarctation of the aorta--a theoretical and experimental analysis of the effects of a centrally located arterial stenosis. AB - Aortic coarctation is a local constriction of the aorta that may severely affect haemodynamics. It is therefore important to quantify these effects. Using Bernoulli's equation and the momentum theorem, the pressure drop is described including the pressure recovery distal to the coarctation and the effects of collateral flow; both laminar and turbulent. Assuming the coarctation and collaterals to be stiff, a quadratic relationship between flow and pressure drop is expected for flow through the coarctation and for turbulent collateral flow. For laminar collateral flow, a linear relationship is expected. The coarctation flow was studied in a model consisting of a rigid tube with local constriction, connected to a flooded-level tank, containing a 36 per cent by weight solution of sucrose, with a viscosity equivalent to that of blood at body temperature. The pressure drop across the constriction showed a quadratic relationship to flow in agreement with theoretical expectations. Pressure recovery in this model was very slight (0-4 mm Hg). Nine patients with aortic coarctation were catheterised. Cardiac output and pressure drop across the coarctation were measured at rest and during supine cycle exercise at two different workloads. The relationship between mean pressure drop and cardiac output tended to be either 'parabolic' or, in some cases, approximately linear, suggesting that the flow situation in aortic coarctation can be quantified by expressions that either linearly or quadratically relate pressure and flow. PMID- 1943262 TI - Estimation of bladder wall location in ultrasound images. AB - A method of automatically estimating the location of the bladder wall in ultrasound images is proposed. Obtaining this estimate is intended to be the first stage in the development of an automatic bladder volume calculation system. The first step in the bladder wall estimation scheme involves globally processing the images using standard image processing techniques to highlight the bladder wall. Separate processing sequences are required to highlight the anterior bladder wall and the posterior bladder wall. The sequence to highlight the anterior bladder wall involves Gaussian smoothing and second differencing followed by zero-crossing detection. Median filtering followed by thresholding and gradient detection is used to highlight as much of the rest of the bladder wall as was visible in the original images. Then a 'bladder wall follower'--a line follower with rules based on the characteristics of ultrasound imaging and the anatomy involved--is applied to the processed images to estimate the bladder wall location by following the portions of the bladder wall which are highlighted and filling in the missing segments. The results achieved using this scheme are presented. PMID- 1943263 TI - Computerised method for acquisition and display of gastrointestinal motility data. AB - A computerised system is developed for the acquisition and display of gastrointestinal motility data which utilises a purpose developed software program called 'PC-motil', running on an IBM compatible microcomputer. 'PC-motil' displays data during collection, writes data to disk file and compresses all data at the end of a study on to a single monitor screen for convenient overview. Any area of interest, in single or multiple channels, may be selected and expanded for detailed examination. This system is tested by the recording of gastric and jejunal motility patterns of 11 healthy volunteers in fasting and fed states. All antral and jejunal migrating motor complexes (MMCs) in fasting studies, as well as all fed motility patterns were recognisable in both 'compressed' and 'expanded' form. The reproduction of motility patterns by the computer based system was indistinguishable from that of a conventional analogue chart recorder. This computerised system provides a convenient and cost-effective means of acquisition, storage and display of motility data in digital form. PMID- 1943264 TI - Serial lung model for simulation and parameter estimation in body plethysmography. AB - A serial lung model with a compressible segment has been implemented to simulate different types of lung and airway disorders such as asthma, emphysema, fibrosis and upper airway obstruction. The model described can be used during normal breathing, and moreover the compliant segment is structured according to more recent physiological data. A parameter estimation technique was applied and its reliability and uniqueness were tested by means of sine wave input signals. The characteristics of the alveolar pressure/flow patterns simulated with the model agree to a great extent with those found in the literature. In the case of absence of noise the parameter estimation routine produced unique solutions for different simulated pathologic classes. The sensitivity of the different parameters depended on the values belonging to each class of pathology. Some more simplified models are presented and their advantages over the complex model in special types of pathology are demonstrated. Noise added to the simulated flow appeared to have no influence on the estimated parameters, in contradiction to the effects with noise added to the pressure signal. In that case effective resistance was accurately estimated. Where parameters had no influence, as for instance upper airway resistance in emphysema or peripheral airway resistance in upper airway obstruction, the measurement accuracy was less. In all other cases, a satisfactory accuracy could be obtained. PMID- 1943265 TI - Algorithm for calculating left ventricular mechanical and energetic characteristics. PMID- 1943266 TI - Multichannel DC amplifier for a microprocessor electroencephalograph. PMID- 1943267 TI - Integer coefficient bandpass filter for the simultaneous removal of baseline wander, 50 and 100 Hz interference from the ECG. PMID- 1943268 TI - The effect of physician-patient communication on mammography utilization by different ethnic groups. AB - The differential utilization of screening mammography by racial/ethnic groups was examined through 35-minute bilingual, random digit dialed telephone interviews with 1,057 women over age 35 years. Results showed that 71% of hispanic women had never had a mammogram and that only 27% over age 50 years had had one in the year before the survey. White and black women over the age of 50 years were being screened more frequently with 34% of white women and 36% of black women having had a mammogram in the prior year. More than half of the hispanic women over age 50 years had never had a mammogram. Analyses showed that the most important variable that predicted whether women of all racial groups had a mammogram, at any time or within the last year, was whether their doctors had discussed mammography with them. The discussion did not need to be lengthy or complex. Hispanic women, however, were less likely to have physicians who discussed screening with them even though these women reported that they were just as motivated as other women to get a mammogram if their doctor referred them. Suggestions for what primary care physicians can do to increase mammography rates, especially among hispanic women, are discussed. PMID- 1943269 TI - Sex differences in patients' and physicians' communication during primary care medical visits. AB - This study reports on the analysis of audiotapes of 537 adult, chronic disease patients and their 127 physicians (101 men and 26 women) in a variety of primary care practice settings to explore differences attributable to the effects of the patient's and the physician's sex on the process of communication during medical visits. Compared to male physicians, women conducted longer medical visits (22.9 vs 20.3 minutes; F(1,515) = 7.9, P less than .005), with substantially more talk F(1,518) = 19.5, P less than .000. Differences were especially evident during the history segment of the visit when female physicians talked 40% more than male physicians (F(1,518) = 20.1, P less than .000) and when patients of female physicians talked 58% more than male physicians' patients (F(1,448) = 24.4, P less than .000). Compared to male physicians, female physicians engaged in more positive talk, partnership-building, question-asking, and information-giving. Similarly, when with female compared to male physicians, patients engaged in more positive talk, more partnership-building, question-asking, and information-giving related to both biomedical and psychosocial topics. PMID- 1943270 TI - Coronary artery bypass surgery: the relationship between inhospital mortality rate and surgical volume after controlling for clinical risk factors. AB - This study uses a new database containing clinical risk factors for cardiac surgery to investigate the relationship between surgical volume (hospital and surgeon) and inhospital mortality rate for all patients receiving coronary artery bypass surgery in New York State in 1989. Also, hospitals with significantly higher and lower mortality rates than expected on the basis of patient preoperative risk factors are identified. The results demonstrate that both annual surgeon volume and annual hospital volume are significantly (inversely) related to mortality rate. The 36% of all coronary bypass operations performed in hospitals with annual bypass volumes of 700 or more by surgeons with annual bypass volumes of 180 or more had a risk-adjusted mortality rate of 2.67% in comparison to a risk-adjusted mortality rate of 4.29% for other bypass operations. Furthermore, low surgical volumes were a major contributor to the outlier status of four of the five hospitals with significantly higher mortality rates than expected. PMID- 1943271 TI - Using clinical variables to estimate the risk of patient mortality. AB - The Health Care Financing Administration (HCFA) uses information from hospital bills, such as age, sex, and diagnoses, to estimate statistical models for the probability, or risk, of death during and after hospital stays. The average risk estimates (expected death rates) are compared with the actual death rates to identify potentially poor quality of care. However, the methods have been criticized as inadequate and an often cited reason is the failure to incorporate risk factors for mortality that are known from clinical research. This hypothesis was tested using a stratified, random sample of 41,963 Medicare patients in 84 hospitals. Many clinical measurements were abstracted for testing as possible risk factors, and a few (26) were identified as useful predictors of death using logistic regression. The estimated regressions accounted for 39% of the variation in mortality, a standard severity classification accounted for 29%, and a relatively simple classification of patients into 17 groups, based on diagnoses, accounted for 17%. The logistic regressions yielded more accurate estimated mortality rates than the severity classification, which in turn was superior to the estimation methods used by HCFA. The HCFA methods were found to be biased in identifying outlier hospitals and this bias can be removed or ameliorated by using clinical risk factors to predict mortality. It is possible to estimate the risk of death more accurately using clinical risk factors and to measure the quality of care. PMID- 1943272 TI - Care seeking for musculoskeletal and respiratory episodes in a Medicare population. AB - Responses to episodes of musculoskeletal illness, musculoskeletal injury, and respiratory illness are examined separately. Data are from a 1-year longitudinal study of the illness experiences of 885 Medicare recipients. Unlike studies examining aggregate use of medical services, this study examines both episodes for which medical care was sought and episodes for which no medical care was sought. Both factors associated with the decision to seek medical care for each type of episode and the illness response patterns associated with whether medical care is sought are analyzed. The three types of episode have different characteristics and profiles of illness response. Perceived seriousness and duration of the episode are the best predictors of physician visits for all episode types. However, the relative effect of predisposing and need variables on the decision to seek medical care is greatest for musculoskeletal illness episodes. These data also bear on the relationship between self-care, informal care, and the use of formal medical care. Use of nonprescription medications is shown to substitute for medical care in a significant number of illness episodes. Lay consultation and restricted activity are often linked with physician visits; however, they cannot be assumed to precede care seeking. The analytic strategy of examining responses to specific types of episodes suggests that both characteristics of the person and characteristics of the illness affect how people respond to illnesses and that the relative importance of each type of characteristic is specific to each illness type. Implications of these findings for health education are discussed. PMID- 1943273 TI - Physicians' communication and parents' evaluations of pediatric consultations. PMID- 1943274 TI - Functional status versus utilities in survivors of myocardial infarction. PMID- 1943275 TI - [Hepatitis: a challenge for the scientific community]. PMID- 1943276 TI - [The spectrum of liver disease in infection by the human immunodeficiency virus: a study of 50 liver biopsies]. AB - BACKGROUND: The patients with human immunodeficiency virus (HIV) infection have hepatic abnormalities due to infective, neoplastic and toxic disorders. The aim of the present study was to describe the spectrum of liver disease in the HIV infection and to establish the usefulness and indications of hepatic biopsy. METHODS: The hepatic biopsies prospectively carried out in 50 patients infected by HIV with abnormal hepatic biochemical parameters, fever of unknown origin or space occupying lesions were evaluated. RESULTS: Hepatic granulomatosis was found in 37 patients (74%). In 15 (30%) the culture in Lowenstein medium was positive. The strains were typified as Mycobacterium tuberculosis in 14. This finding took place in 8 out of 18 biopsies carried out because of fever of unknown origin (FUO) (44%). The rate of granulomatosis due to mycobacteria was 40%. Other diagnoses were steatosis in 22 patients, chronic active hepatitis in 10, chronic lobular hepatitis in 3, infiltration by Hodgkin's lymphoma in one and metastatic invasion by non-differentiated carcinoma in one. Hepatic biopsy was diagnostic in 8 out of 18 carried out for FUO (44%) and in 24 out of 30 carried out for abnormal hepatic biochemical parameters (80%). CONCLUSIONS: In the evaluated patients with HIV infection, hepatic granulomatosis was the most common finding and was due to mycobacteria in 40%. Hepatic steatosis and chronic active and lobular hepatitis were the most common causes of abnormal hepatic biochemical parameters. Considering the high yield of hepatic biopsy, the authors think that it should be carried out in patients with HIV infection and FUO or unexplained abnormal hepatic biochemical parameters. PMID- 1943277 TI - [Psychiatric morbidity in elderly patients admitted to a general hospital. A day prevalence study]. AB - BACKGROUND: The most common psychiatric diseases in the geriatric population are depression, the acute confusional state or delirium and dementia. METHODS: A prevalence-day study of psychopathology was carried out in the elderly population admitted to the hospital for several medical and surgical conditions. The semistructured psychiatric interview (CIS), cognoscitive miniexamination (MEC) and Zung's depression scale (SDS) were administered. When appropriate, a diagnosis was established following the DSM-III-R criteria. 15% of the overall number of elderly patients were excluded because of severe medical disease or surgical operation on the study day. RESULTS: A 43% prevalence of psychiatric disorders was found. 21% of them had depression and 18% a mental organic disorder with cognitive deficit in the form of dementia (6%), delirium (10%), or both (2%). The depression symptoms were more marked with greater cognitive deterioration, and both were greater with increasing age. In only 10% of the patients considered as psychiatric cases the cooperation of the psychiatric interconsultation team had been requested. CONCLUSIONS: The diagnosis of these diseases (depression, delirium and dementia) is very important because in the elderly population with these disorders a higher morbidity and mortality due to medical causes is found. PMID- 1943279 TI - [Antiphospholipid syndrome: an evolving entity]. PMID- 1943278 TI - [Mycobacterial infections: yield of bacillary microscopy in different clinical samples (1975-1988)]. AB - BACKGROUND: The yield of microscopy examination as a quick diagnostic test in several pulmonary and nonpulmonary samples referred to the mycobacterial laboratory of a general hospital is reviewed. METHODS: During a 14-year period (1975-1988), 113,836 biological products were investigated. In 9,972 a positive culture for mycobacteria was obtained. For the microscopy examination the auramin technique was used; if positive, acid-alcohol resistance was confirmed by overstaining with the Ziehl-Neelsen technique. The culture was used as the reference method. RESULTS: Microscopic examination was positive in 34% of samples with a positive culture, being 39% for Mycobacterium tuberculosis and 10% for environmental mycobacteria. The overall specificity was 99%, the positive predictive value was 91% and the negative predictive value was 94%. In pleuropulmonary samples the sensitivity ranged from 48% in sputum and 2% in pleural biopsy, with specificity higher than 99%. In nonpulmonary samples, sensitivity, specificity and positive and negative predictive values varied with the type of sample. The false positive rate (positive microscopy with negative culture) was 0.3, and it was shown that 80% of these patients had received previous therapy. In organic fluids (pleural, peritoneal, cerebrospinal), the sensitivity was not greater than 13%. CONCLUSIONS: Sputum, bronchoaspirate and bronchoalveolar lavage were better for the diagnosis of tuberculosis than gastric aspirate. Approximately 1 in each positive microscopy examinations corresponded to environmental mycobacteria. In some nonpulmonary samples with high sensitivity the positive predictive value was low. 80% of the false positive results corresponded to previously treated patients. PMID- 1943280 TI - [Cerebral tuberculoma. Report of 8 cases]. AB - A series of eight patients with cerebral tuberculoma seen between 1980 and 1990 is reported. Headache was the leading clinical finding, followed by focal neurological findings and seizures. Papilledema was the most uniform examination finding associated with intracranial hypertension. Five patients had another localization of tuberculosis: three had tuberculous meningitis, one had tuberculous pericarditis and only one had associated active pulmonary involvement. Cerebrospinal fluid was investigated in seven patients. In three patients data of tuberculous meningitis were found, with positive culture in Lowenstein medium. Two patients had the acquired immunodeficiency syndrome. All patients received medical treatment with good response, except in one who developed paradoxical expansion of the lesions after two months of therapy. PMID- 1943281 TI - [Phases of the clinical trial in oncology]. PMID- 1943282 TI - [Diffuse infiltrative pulmonary disease and pleural effusion in a 31-year-old woman]. PMID- 1943283 TI - [Phosphorus-calcium metabolism in active pulmonary tuberculosis]. PMID- 1943284 TI - [Tardive dyskinesia due to sulpiride]. PMID- 1943285 TI - [Lymphoma with bilateral orbital tumors]. PMID- 1943286 TI - [Meningovascular syphilis and human immunodeficiency virus infection]. PMID- 1943287 TI - [Anticholinergic syndrome from poisoning by Datura stramonium]. PMID- 1943288 TI - [Immunoglobulin A as a prognostic factor in infection by human immunodeficiency virus type 1]. PMID- 1943289 TI - [Epidemiological surveillance of viral hepatitis in Catalonia]. PMID- 1943290 TI - [Hallucinosis due to trihexyphenidyl abuse]. PMID- 1943291 TI - [Yersiniosis in a general hospital in the Basque country (1984-1989). Clinical and epidemiological aspects]. AB - BACKGROUND: The features of the diseases caused by Yersinia have not been properly evaluated in the Basque Country. The present study was performed to assess the incidence and consequences of this infection. METHODS: 51 cases of Yersinia infection in a general hospital during the period 1984-1989 were reviewed. Clinical, epidemiological, microbiological, and therapeutic data and the hospital stay were evaluated. RESULTS: 62% of patients were males with a mean age of 16 +/- 19.4 years. Most came from urban areas. 40% of cases developed in winter and 32% in summer. The presenting features were: acute gastroenteritis (66%), pseudoappendicitis (10%), sepsis (4%), lymphadenopathy (2%) and others (18%). 40% of the patients had significant underlying diseases, and 16% had complications attributable to the infection. The microbiological diagnosis was made by stool culture in 88%. 96% corresponded to Yersinia enterocolitica (biotype 4), serogroup 0: 3 (93%). Yersinia pseudotuberculosis was isolated from the culture of a cervical lymph node in one patient. In the Yersinia enterocolitica strains the most common antibiotic resistances were to ampicillin (87%), cephalotin (81%), ticarcillin (75%), mezlocillin (43%) and piperacillin (43%). The mean hospital stay was 6.1 +/- 12.2 days and it was significantly shorter in children (3.3 +/- 6.1%) than in the adult population (10.9 +/- 17.4) (p less than 0.05). It was longer in patients with underlying diseases (13.3 +/- 17.8 vs 3.3 +/- 5.6) (p less than 0.005). CONCLUSIONS: Our patient population had male and urban predominance. Most infections were caused by Yersinia enterocolitica and presented as acute gastroenteritis, without differences between winter and summer. We point out to the relationship between Yersinia infection, abnormalities in iron metabolism and immunosuppression. There were few complications of the infection. The mean hospital stay was directly correlated with age and underlying diseases. PMID- 1943292 TI - [Alterations in calcium metabolism in patients with active tuberculosis]. AB - BACKGROUND: Abnormalities in phosphocalcic and vitamin D metabolism may develop in patients with active tuberculosis (TB). Their incidence and relationship with the disease is not well known, particularly in our area. We have prospectively evaluated 40 patients with TB [(30 with localized TB (LTB) and 10 with disseminated TB (DTB)]. METHODS: After stabilizing the diet during 4 days, the calcium, phosphorus, magnesium and creatinine balances, blood ionic calcium, plasma intact PTH, 25-hydroxy vitamin D [25(OH)D] and serum 1.25 dihydroxyvitamin D [1.25(OH)2D] were measured. RESULTS: Hypercalcemia was not found in any patient, but 25% had hypercalciuria (HC). The 24-hour urinary excretion of calcium was higher in patients than in controls (3.2 +/- 1.7 mg/kg or 0.10 +/- 0.06 mg/100 ml of GFR vs 2.3 +/- 0.7 mg/kg or 0.08 +/- 0.03 mg/100 ml of GFR, p less than 0.05), basically at the expense of patients with DTB (4.4 +/- 1.8 mg/kg or 0.14 +/- 0.06 mg/10 ml of GFR, p less than 0.005). These had a lower PTH than patients with LTB and controls (12.8 +/- 7.7 vs 18.5 +/- 6.9 vs 19.5 +/- 6.0 pg/ml, p less than 0.05). Independently from the extent of the disease, the patients with HC had a lower PTH (12.6 +/- 6.8 vs 18.5 +/- 6.9 pg/ml, p less than 0.01) and higher serum 1.25(OH)2D (34.5 +/- 10.1 vs 25.0 +/- 7.2 pg/ml, p less than 0.01) than patients without HC. The levels of 25(OH)D were lower in patients with TB than in controls (11.2 +/- 6.0 vs 20.0 +/- 7.0 ng/ml, p less than 0.05), independently from the extent of the disease and the presence or absence of HC. CONCLUSIONS: Patients with tuberculosis may have hypercalcinuria with inadequately high levels of 1.25(OH)2D and low intact PTH. This abnormality appears to be correlated with the extent of the disease. PMID- 1943294 TI - [Community-acquired pneumonia]. PMID- 1943293 TI - [Prospective study of community-acquired pneumonias seen in a general hospital. Diagnostic errors]. AB - BACKGROUND: The patients with community acquired pneumonias seen in an emergency service of a basic general hospital during one year were evaluated to assess their etiological, clinical and radiological features, and also to investigate the initial and final diagnosis of the disease, its evolution and the parameters associated with each microbiological type. METHODS: A medical team investigated daily the clinical records. For etiologic diagnosis, blood cultures, serological studies, urine counterimmunoelectrophoresis (CIE) and, in individualized patients, pleural fluid culture, bronchoaspirate and bronchoalveolar lavage were performed. The discordance between the initial clinical and radiological diagnosis and the microbiological results, and also the initial and final diagnostic errors were analyzed. RESULTS: 311 cases of pneumonia (150 adults and 161 children) were diagnosed. 95 (30%) had microbiological confirmation. Streptococcus pneumoniae was the most commonly isolated organism. Serologic studies were the diagnostic method with the highest yield. Complications developed in 28% of the patients and the mortality rate was 2%. There was a relationship between mortality and a high respiratory rate on admission. The initial-final diagnostic discrepancy was 43% in atypical pneumonias and 40% in bacterial pneumonias. CONCLUSIONS: Clinical parameters permitting the differentiation between atypical and bacterial pneumonia were not found. The initial diagnostic error was 12%, consisting of false positives in all instances, and the final diagnostic error included 15% false positives and 10% false negatives. Underlying diseases have a influence on the evolution of pneumonia. The mean respiratory rate on admission should be measured as a prognostic indicator. In the present study, urine CIE was a poorly sensitive method. PMID- 1943295 TI - [Yersiniosis]. PMID- 1943296 TI - [Bacteremia from Campylobacter fetus. Increasing interest and incidence]. AB - Three bacteremias of Campylobacter fetus were described. One was a male patient and two were females. Underlying illnesses were present in all of them (Hodgkin disease, AIDS and hepatic cirrhosis respectively). They were all admitted because of fever and no other symptoms of infectious focus were present. Physical findings were not relevant. The blood cultures became positive in days 6, 7 and 9 respectively. Antibiotic treatments were not standardised, so no conclusions can be drawn. The evolution was correct except for the patient infected by the human immunodeficiency virus who carried out a recurrent course. The authors comment on the increasing interest of this pathogen causing extraintestinal infection. PMID- 1943297 TI - [Biomedical documentation: structure and operation of bibliographical databases]. PMID- 1943298 TI - [Is it useful to monitor the plasma concentrations of aminoglycosides?]. PMID- 1943299 TI - [Neutropenia caused by ciprofloxacin and Escherichia coli bacteremia. Bone marrow examination]. PMID- 1943300 TI - [The shrunken lung, a little known respiratory manifestation of systemic lupus erythematosis]. PMID- 1943301 TI - [Prehospital fibrinolysis in acute myocardial infarction]. PMID- 1943302 TI - [Hepatitis A virus encephalitis]. PMID- 1943303 TI - [Blood donation in the Balearic Islands. Analysis of supply and demand of blood from 1982 to 1987]. AB - BACKGROUND: The supply and consumption of blood products in the autonomous community of the Balearic Islands were evaluated for the years 1982 to 1987 to assess the degree of hemotherapy coverage. METHODS: The registries of blood banks from 1982 to 1987, the clinical records of patients with congenital coagulation deficiencies and the registries of the hospital pharmacies and pharmaceutic distributing agencies were reviewed. RESULTS: The rates of use per product (units) and per one thousand population were as follows: red blood cells 22-25, platelets 0.8-3.2, transfusional plasma 0.5-2.8, and cryoprecipitates less than 0,2. The consumptions of albumin and gammaglobulins were 80 and 7.7 kg per one million population, corresponding to 3.200 and 1.540 I of plasma, respectively. The consumption of factor VIII was 1.3-0.9 international units (IU) per inhabitant, in highly of very highly purified form, corresponding to 18.500 12.857 I of plasma. CONCLUSIONS: The results show that a supply of 25-27 blood donations per one thousand population and per year and with a fractionning of 80%, yield 5.000 I of plasma per one million population. This fulfils the needs of all blood products, except those of highly or very highly purified factor VIII. PMID- 1943304 TI - [Infective morbidity of replacement therapy in congenital coagulation deficiencies and its effects on demand of coagulation factors]. AB - BACKGROUND: Analysis of the infective morbidity and mortality secondary to replacement hemotherapy in the population with congenital coagulation deficiencies (CCD) and their consequences on the demand for coagulation factors. METHODS: The 46 patients with CCD diagnosed in the autonomous community (AC) of the Balearic Islands (32 with hemophilia A, 6 with hemophilia B, 4 with von Willebrand's disease 2 with factor VII, 1 with factor X, and 1 with factor XII deficiencies) were investigated for infective morbidity and use of blood products from 1982 to 1987. RESULTS: 97% of the patients had some hepatitis marker, 77% had antibodies against human immunodeficiency virus (HIV) and 17% fulfilled the criteria for the acquired immunodeficiency syndrome (AIDS). There were 7 deaths (15%). The morbidity and mortality increased with age and use of blood products. There was a 46% reduction in factor VIII use between 1982 and 1986, from a mean yearly consumption per hemophiliac patient of 33444 international units (IU) to 18080 IU. CONCLUSIONS: The study results show a high prevalence of hepatitis and HIV, an important reduction in the demand of manufactured coagulation factors and a 15% reduction in the population with CCD during the study years. PMID- 1943305 TI - [Variability of arterial pressure and of heart rate in essential arterial hypertension]. AB - BACKGROUND: Blood pressure (BP) and heart rate (HR) show multiple oscillations. The aim of the present study was to evaluate their variability by means of a noninvasive device for the continuous recording of ambulatory BP. METHODS: A 24 hour recording was programmed (minimal interval 30 minutes) in 190 individuals: 35 normotensive individuals aged 46 +/- 20 years and 155 patients with essential hypertension aged 49 +/- 12 years. RESULTS: In the whole population a significant positive correlation was found between systolic BP (SBP) and its variability (r = 0.360; p less than 0.001). This correlation was found for both normotensive (r = 0.506; p less than 0.01) and hypertensive (r = 0.384; p less than 0.001) groups. There also was significant positive correlation between HR and its variability in the overall population (r = 0.374; p less than 0.001) and in the normotensive (r = 0.594; p less than 0.001) and hypertensive (r = 0.356; p less than 0.001) groups. There was a significant positive correlation between SBP and age in the whole population (r = 0.269; p less than 0.001) and in the normotensive (r = 0.448; p less than 0.001) and hypertensive (r = 0.193; p less than 0.05) groups. When the individuals were divided in those older than 65 years and those younger than 60 years, with same levels of SBP and DBP, it was found that the variability (given as standard deviation) of both SBP and DBP were higher in the older group (similar SBP: 19 +/- 7/13 +/- 4 mmHg vs 15 +/- 4/11 +/- 3 mmHg, p less than 0.01/p less than 0.01; similar DBP: 19 +/- 7/13 +/- 4 mmHg vs 15 +/- 5/11 +/- 3 mmHg, p less than 0.001/p less than 0.01). Multiple regression analysis showed that the most important determinant of this variability was the baseline SBP value, followed by age. CONCLUSIONS: SBP and HR show a greater variability with higher baseline values. The variability of both SBP and DBP are greater in elderly patients. PMID- 1943306 TI - [The need of human plasma]. PMID- 1943307 TI - [Tobacco and thrombosis: data for an association]. PMID- 1943308 TI - [Stress and depression]. PMID- 1943309 TI - [Acquired immunodeficiency syndrome and cutaneous porphyria tarda]. PMID- 1943310 TI - [Spontaneous splenic rupture in non-Hodgkin's lymphoma: diagnosis with computerized tomography]. PMID- 1943311 TI - [Evaluation of rheumatoid arthritis treatment with methotrexate by survival analysis]. PMID- 1943312 TI - [McArdle disease. Report of a case]. PMID- 1943313 TI - [Classic migraine as first symptom of spirochete infection]. PMID- 1943314 TI - Management of the patient with tinnitus. AB - Management of the patient with tinnitus is an extremely perplexing problem. This article discusses the evaluation and therapeutic considerations currently used. PMID- 1943315 TI - Update in otolaryngology I. PMID- 1943316 TI - Sudden sensorineural hearing loss. AB - Hearing is one of our most important senses and its sudden loss can be frightening and frustrating for the patient and his or her physician. Despite multiple reports of sudden SNHL over the years, we still do not have a universally accepted definition. This has led to further confusion in reporting and evaluating the treatment and prognosis of this disease. We generally define any SNHL occurring over 3 days as sudden SNHL. The overall incidence of this disease appears to be low. However, the true incidence may be higher, because those patients who spontaneously recover may never seek medical attention. The etiology is often difficult to identify, leaving a large population of patients labeled as idiopathic SNHL. Before accepting the idiopathic label, the physician must maintain a high level of suspicion to be sure that the SNHL is not a symptom of a larger underlying systemic disorder. Several theories have been proposed to try to explain SNHL. These include the infectious theory, vascular theory, and rupture theory. In addition to these, metabolic imbalances, drug toxicity, and various disease entities may contribute to sudden SNHL. Over the years, many treatment protocols have appeared in the literature, each claiming various rates of success. Unfortunately, they are often based on emotional and empiric considerations, because an exact etiology is unknown. Drugs have been chosen from several categories including the following: vasodilators, diuretics, anticoagulants, plasma expanders, corticosteroids, and contrast material. These medications have been used singly or in combination therapies. One must always be aware of the potential side effects. One factor that appears to be constant in each reported therapy is that those patients who seek medical attention early do better. The type of hearing loss also seems to play a role in the outcome of sudden SNHL; patients with low-frequency hearing losses or upward-sloping audiograms have a better prognosis. The patient must take the first step in seeking medical attention. Once the problem has been recognized, prompt attention by the physician to the medical workup and timely initiation of therapy will offer the patient the best possible chance for recovery. Time is often the greatest factor in the overall recovery, and the physician should reassure the patient that everything is being done to speed this along. However, patience may be the greatest healer of all. PMID- 1943317 TI - The dizzy patient. Update on vestibular disorders. AB - Dizziness is often a patient's shorthand description of a variety of symptoms, many of which have nothing to do with balance. Vertigo consists of an abnormal sensation of motion, whereas dysequilibrium is a disturbance of balance without necessarily a sensation of motion. A careful history usually determines the nature of the patient's presenting symptoms, and a thorough workup will often give rise to a diagnosis. Vertigo of vestibular origin may be treated with a variety of medications or, when these fail, surgery. Surgery should preserve hearing when at all possible. Balance rehabilitation is a useful modality for the patient who does not compensate spontaneously or who does not respond to the medical or surgical treatment of imbalance. PMID- 1943318 TI - Implantable hearing devices. AB - The use of implantable hearing devices to help persons with hearing loss is still in its infancy. The advantages and disadvantages of various models of implantable hearing devices currently being developed are discussed, and their clinical use is described. Other hearing aid assistive devices are also discussed, particularly the electromagnetic implant hearing aid. PMID- 1943319 TI - Cochlear implants: indications and technology. AB - Over the last decade, the field of cochlear implants has progressed to the point where many postlinguistically deaf adults can use a multichannel device to understand speech without lipreading. The remainder are able to use their devices to aid in lipreading and to discriminate environmental sounds. It is anticipated that improved processing schemes will be developed so that the cochlear implant user can expect better speech perception with these devices. Eventually, a more sophisticated cochlear implant that has the capability of permitting good speech discrimination may supplant hearing aids for severely deafened individuals. Regardless of future developments, the present-day systems effectively restore auditory function to profoundly deafened children and adults. PMID- 1943320 TI - Chronic otitis media: diagnosis and treatment. AB - Very few problems are as frustrating as persistent otitis media and the draining ear. The draining ear may present in a variety of ways and may persist despite the use of routine otic drops and oral antibiotics. This article addresses the medical and surgical options available in the management of otitis media and its complications. PMID- 1943321 TI - Update on diagnosis and treatment of sinus disease: the functional endoscopic sinus surgery approach. AB - This article presents the latest techniques used to provide more accurate diagnosis and medical therapy for the patient with sinus disease. These techniques also provide the tools for performing more meticulous surgery and precise postoperative care and follow-up for patients with a multitude of sinus symptoms. The methods of diagnosis and medical management, indications and technique of surgery, and postoperative care and results are discussed. PMID- 1943322 TI - Practical management of epistaxis. AB - Epistaxis is a very common presenting symptom of patients seen in the emergency room or the physician's office. An understanding of the nasal anatomy and physiology is important for proper treatment of these patients. New methods of treatment are discussed briefly. PMID- 1943323 TI - Disorders in taste and smell. AB - Although many conditions and medications have been associated with chemosensory disturbances, data from major chemosensory clinical research centers support three major disorders as being causative: nasal and paranasal sinus disease (21%), post-upper respiratory tract viral infection (19%), and head trauma (14%). Despite extensive evaluation, 22% of patients do not demonstrate identifiable causation. PMID- 1943324 TI - Computed tomography versus magnetic resonance imaging and three-dimensional applications. AB - An attempt has been made to simplify and to provide an understanding of some of the new modalities for evaluation of head and neck pathology. Both CT and MRI are complementary to each other: MRI being superior to CT in evaluating soft tissue, and CT being superior to MRI in assessing fine bony details and in identifying microcalcifications. MRI is the modality of choice for tumor evaluation because it has several advantages over CT in assessing the location, spread, and staging of the disease. HRCT scanning remains the procedure of choice in the evaluation of middle ear and base of the skull, and in the evaluation of benign sinonasal disease. CPA and IAC lesions are best evaluated by MRI. Three-dimensional surface reformations of axial CT scans enable the surgeon to plan the operative approach needed to reduce facial fractures and to repair cranial deformities. PMID- 1943325 TI - Snoring and obstructive sleep apnea. AB - Evidence shows that snoring and obstructive sleep apnea have significant negative physiologic consequences. These patients should be treated expeditiously once the diagnosis is made and carefully followed to ensure that improvement is maintained. PMID- 1943326 TI - Otolaryngologic (head and neck) problems in the elderly. AB - This article is designed to give the reader an appreciation of some of the more common or important facets of the management of head and neck disorders in the elderly patient. Readers are referred to the references for more detailed descriptions of the topics. PMID- 1943327 TI - Otolaryngologic aspects of acquired immunodeficiency syndrome. AB - Currently, most patients with AIDS present with a manifestation involving the head, neck, or respiratory tract. The otolaryngologist may be the first physician to evaluate the patient with HIV infection and, therefore, must be aware of the various manifestations. The otolaryngologist may also be involved in diagnosing and managing the disease through modalities such as biopsy, endoscopy, tracheotomy, and other surgical procedures. In all phases of care, it is important to retain a medically appropriate and psychologically supportive environment. Although universal precautions should be followed in all phases of care, there is no need to avoid the supportive gestures such as handshaking and shoulder patting. These contacts can be most comforting to patients. Physicians should also be aware of all sources of information and medical assistance within the community that might be of further assistance to patients. The AIDS epidemic presents an enormous challenge to all health care providers. Good interdisciplinary communication among the various specialists involved in the AIDS epidemic will promote increased standards of patient care. Such communication will also provide information and support for physicians who are uncomfortable with the challenges of this epidemic. PMID- 1943328 TI - Development of male-fertility-regulating agents. PMID- 1943329 TI - Use of microorganisms for the study of drug metabolism: an update. AB - The use of microorganisms as tools in the study of drug metabolism appears to be gaining popularity. The selected examples cited here provide additional evidence of the utility of these systems as alternative in vitro models for studying drug metabolism in humans. However, as was noted earlier, this model, nor any other in vitro model system could ever replace animals in biomedical research. However, it is apparent from the numerous examples cited here and in the previous review of this area that microorganisms are a reliable, reproducible alternative to small animals as predictive models in drug metabolism studies. The continuing development of techniques that reduce the use of animals in research is encouraged and this procedure appears to be gaining more widespread acceptance for such use. PMID- 1943330 TI - [An unequivocal answer to an inquiry: keep the psychotherapy courses in the education of psychiatrists]. PMID- 1943331 TI - [Bottom quotation for Swedish medical research in the "citation league"]. PMID- 1943332 TI - [Bone marrow transplantation: unrelated donors are good but the risk of graft versus host reaction is increased]. PMID- 1943333 TI - [Analyses of narcotics in urine--valuable if correctly done and competently used]. PMID- 1943334 TI - [Basalioma and radiotherapy]. PMID- 1943335 TI - [Puncture biopsies must not be abused]. PMID- 1943336 TI - [Knowledge about sexual abuse--oddities from the National Board of Health and Welfare]. PMID- 1943337 TI - [Quality control supports carotid surgery even in Sweden]. PMID- 1943339 TI - [The SBU (a Swedish committee for the evaluation of medical methods) report on bone marrow transplantation: there are obvious ethical problems]. PMID- 1943338 TI - [A Scandinavian pool for unrelated bone marrow donors--organization and recruiting of donors]. PMID- 1943340 TI - [Histoplasmosis--a review in connection to some imported cases]. PMID- 1943341 TI - [The man behind the syndrome. Samuel T. Darling--the discoverer of histoplasmosis. An energetic specialist of tropical medicine with many international assignments]. PMID- 1943342 TI - [Use and abuse of substance abuse analyses in urine]. PMID- 1943343 TI - [A mild influenza season 1990/91. A new vaccine will be produced for the season 1991/92]. PMID- 1943344 TI - [As I remember my dissertation]. PMID- 1943345 TI - [Younger physicians need better leadership]. PMID- 1943346 TI - [3 reports on population health. Who will take care of my health?]. PMID- 1943347 TI - [The molecular background of our capacity to identify smells]. PMID- 1943348 TI - [Endoscopic intervention should be considered in acute gallstone pancreatitis]. PMID- 1943349 TI - [How to get rid of Nicorette?]. PMID- 1943350 TI - [Still unnecessary dosage errors in the administration of insulin]. PMID- 1943351 TI - [To describe one's problem for the doctor]. PMID- 1943352 TI - [Children in the poor world--to die now, survive in misery or with some quality of life?]. PMID- 1943353 TI - [Do we relieve short-sightedly and increase the misery in the long run?]. PMID- 1943354 TI - [Mictrol is withdrawn after adverse cardiac effects. An account of Swedish cases]. PMID- 1943355 TI - [Epidermal necrolysis suspected as a new adverse effect of Cardizem]. PMID- 1943356 TI - [Treatment of depression. Recommendations from a meeting of experts]. PMID- 1943357 TI - [Cases of patient insurance in the USA: erroneous diagnosis of colorectal cancer as a common cause of expensive compensation cases]. PMID- 1943358 TI - [Dissertations--time for reforms?]. PMID- 1943359 TI - [The risk of transmission is higher for the physician than for the patient]. PMID- 1943360 TI - [A warning against unnecessary autopsies?]. PMID- 1943361 TI - [More poultry is hardly less fat]. PMID- 1943363 TI - [A course in agricultural activities for the mentally handicapped increases their quality of life]. PMID- 1943362 TI - [Skin cancer around the nose and ears: careful curettage followed by cryosurgery is a cheap and safe therapeutic method]. PMID- 1943364 TI - [Catheter ablation--a first choice alternative in supraventricular tachycardias?]. PMID- 1943365 TI - [Drug-dependent mental patients often fail to obtain adequate psychiatric care]. PMID- 1943366 TI - [The majority of the men undergoing vasectomy are satisfied 10 years after the intervention]. PMID- 1943367 TI - [Magnetic resonance tomography. A valuable method in the diagnosis of central nervous system diseases in children]. PMID- 1943368 TI - [A trial to prevent cancer and STD among 21-year-old subjects. The difficulty of getting young males to participate in health check-ups at clinics for young people]. PMID- 1943369 TI - [Quality assurance in the care of diabetes. The necessity for health centers and hospitals to have a common information system]. PMID- 1943370 TI - [Quality assurance in long-term oxygen therapy. Registries make evaluation of indications, complications and survival possible]. PMID- 1943371 TI - [Good experiences with an open house for patients with infectious diseases]. PMID- 1943373 TI - [Patient records on "smart cards"--a new technology in health care]. PMID- 1943372 TI - [Acute intermittent porphyria--clinical, chemical and molecular biological research, past and present]. PMID- 1943374 TI - [Research at Sweden's lung clinics. Increased resources are needed for deeper research]. PMID- 1943375 TI - [Esthetic surgery--a commentary]. PMID- 1943376 TI - [Patient records on "smart cards"--security is needed]. PMID- 1943377 TI - [The health center is hopelessly outdated!]. PMID- 1943378 TI - [Are high alkaline phosphatase serum levels in children truly related to the skeleton?]. PMID- 1943379 TI - [Bandages and treatment: the bandage should function as a support of the calf muscle]. PMID- 1943380 TI - [Misleading information on amalgam]. PMID- 1943381 TI - [Lobak--a case of disinformation?]. PMID- 1943382 TI - [Why does Roche forget about half dosages?]. PMID- 1943383 TI - [Transient benign hyperphosphatemia in young children]. PMID- 1943384 TI - [Lysozyme--an enzyme of both historical and current interest as a therapeutical agent]. AB - Lysozyme, a bacteriolytic protein discovered by Fleming in 1922 and found to be phylogenetically ancient and almost ubiquitous among living organisms, is probably the most studied enzyme in biology and medicine. Evidence of its involvement in resistance to bacterial infection is compelling but remains indirect. Muramyl peptides (fragments of bacterial cell wall peptidoglycan) exert many effects on the immune system and the CNS, and appear to contribute to non specific resistance to infection, fever, fatigue, and the pathogenesis of bacterial infection. Synthetic muramyl peptide analogues are currently used as adjuvants in vaccine trials in humans. Several pathological conditions are associated with changes in lysozyme concentrations, and egg-white lysozyme treatment has been tried on a small scale. With the cloning of the human lysozyme gene in yeast cells the enzyme can now be produced on a large scale, which will enable its therapeutic applications to be evaluated. PMID- 1943385 TI - [The man behind the syndrome. Frederic C. Bartter: the mushroom-loving endocrinologist who left little to chance]. PMID- 1943386 TI - [The living heart as a model for a new pump technology]. PMID- 1943387 TI - [Risk of poisoning in subacute therapeutic overdosage of paracetamol]. PMID- 1943388 TI - [Damage caused by prolonged surgery with supported legs]. PMID- 1943389 TI - [Ambulance activities in the county of Skaraborg are improved with the help of military helicopters]. PMID- 1943390 TI - [Children in developing countries--to die now or to survive in misery? Prolonged breast feeding is good against the "population trap". Family planning should not be forced onto developing countries]. PMID- 1943391 TI - [A DRG model at the Kungalv Hospital: an attempt to overcome the gap between the administration and the medical profession]. PMID- 1943392 TI - [Awakening in spite of narcosis--psychological trauma for many years after]. PMID- 1943393 TI - [Questions of war or peace should not be left to the army. The question of life and death should not be left to the philosopher]. PMID- 1943394 TI - [Rehabilitation--warning against adverse effects]. PMID- 1943395 TI - [More and more information about tick-borne encephalitis]. PMID- 1943396 TI - [Importance of controlled studies on liver cancer]. PMID- 1943397 TI - [Malignant rheumatoid vasculitis--a problem of older patients with rheumatoid arthritis]. PMID- 1943398 TI - [Transurethral resection syndrome--a severe complication of the prostatic gland resection]. PMID- 1943399 TI - [Subcutaneous apomorphine--a valuable therapeutic alternative in Parkinson disease]. PMID- 1943400 TI - [Visceral leishmaniasis in an Eritrean refugee child in Sweden]. PMID- 1943401 TI - [Decreased incidence of Chlamydia infection in a primary care district, thanks to screening and reinforced contact tracing]. PMID- 1943402 TI - [A hand surgeon's impressions during a visit to China: high skills, shortages in rehabilitation and the wish to make contacts with the West]. PMID- 1943403 TI - [Stomach ulcer surgery--an interlude in the history of medicine?]. PMID- 1943404 TI - [Tumor of Vater's papilla--a diagnostic and therapeutic challenge]. PMID- 1943405 TI - [Limited surgical radicality in occult cancer of Vater's papilla]. AB - Nine histologically proven benign adenomas of the papilla of Vater were consecutively treated by transduodenal full thickness excision and simultaneous staging of regional lymph nodes without severe postoperative complications. 4 patients had a small well differentiated (pT1 GIpN0) carcinoma, although there was neither macroscopically nor by frozen sections any suspicion of a malignant tumour. A more radical pancreatoduodenectomy was not carried out and the 4 patients are without tumour recurrence or metastases 1-8 years postoperatively. PMID- 1943406 TI - [Ileostomy--stabilization by stapler technique]. AB - In order to prevent nipple-sliding of the everted small bowel, conventional Brooke ileostomies in 26 patients were stabilized on both sides of the mesentery by longitudinal rows of staples. There were no early complications. With respect to historical controls with unstapled ileostomies, late complications (retraction, prolapse) could be reduced from about 16 to 0% in a median observation time of 2 years. The ileostomies were stable in size and form and therefore appliances were facilitated. PMID- 1943407 TI - [Tumor recurrence at the neck in papillary thyroid gland cancer. A statistical analysis of the recurrence probability after radical surgery]. AB - 308 cases of papillary thyroid carcinoma (82.6% of our patients operated on between 1952 and 1987) who had undergone potentially curative surgery were analysed postoperatively. The follow-up ranges from 1 month to 29.4 years (median 4.58 years). In 32 cases (10.4%) a cervical tumour recurrence (local recurrence and/or cervical lymph nodes) was found. 8 of these are not free of tumour at the end of the follow-up, 6 had died of thyroid carcinoma (case fatality rate 18.8%, mortality rate 66.7%, in the entire material 2.9% and 29.0% respectively). The cumulative recurrence rate is 9.98% after 5 years and 16.98% after 10 years. A statistical analysis of the probability of recurrence was carried out only for patients who could be followed at least 5 years or those who died within 5 years. Age, sex, stage of tumour and histological criteria were taken into account as statistical variables. The state of cervical lymph nodes, the differentiation of the tumour and the patients' sex turned out to be determining factors for tumour recurrence after 5 years. In order to improve the recurrence rate a differentiated surgical radicality, depending on the above mentioned variables, is recommended. PMID- 1943408 TI - [Surgical therapy of leiomyosarcoma of the veins. A case report]. AB - Among the rare soft tissue sarcomas the leiomyosarcoma of the veins is only to be found in very few cases. On the basis of a case report the procedure of surgical treatment concerning this tumour is described; usually, in addition to the resection of the compartment a vascular reconstruction is required. PMID- 1943409 TI - [Stomach emptying after stomach resection with and without retention of duodenal passage]. AB - On domestic pigs 2/3 gastrectomies with retention and elimination of the duodenal passage were carried out. Postprandial gastric emptying was measured scintigraphically for 4 h and compared with a control group (laparotomy only). For the semi-solid, 99mTc-labeled test meal delayed gastric emptying after elimination of the duodenal passage by Roux reconstruction could not be shown. There was no difference in gastric emptying between B-I and Roux-en-Y partial gastrectomy. Also alteration of the length of the jejunum loop from 40 to 20 cm after Roux-en-Y reconstruction had no influence on gastric emptying. Roux reconstruction (40 cm loop) in combination with truncal vagotomy led to a non uniform gastric emptying, but there was a statistically proven acceleration compared with B-I resection. After 240 min the mean residual intragastric activity of the control group (n = 5) was 47.8%, 78.9% after B-I resection (n = 5), 59% after Roux reconstruction with 40 cm jejunal loop (n = 5), 38.1% after Roux reconstruction with 20 cm jejunal loop (n = 5) and 20.9% after Roux-en-Y (40 cm loop) with truncal vagotomy (n = 4). PMID- 1943410 TI - [Organ preservation by reconstruction of Wirsung's duct in complete pancreas rupture]. AB - Blunt abdominal traumas with pancreatic injuries often cause partial or subtotal resection of the organ, especially when the pancreatic duct is damaged. A reconstructive method for anastomosis of the duct is reported in a case of a 9 year-old boy with complete pancreatic rupture in which the whole organ could be salvaged. PMID- 1943411 TI - [The effectiveness of hypercaloric and hypocaloric postoperative parenteral nutrition in large abdominal surgery. A prospective randomized study]. AB - By means of a prospective randomised trial protein turnover and general energy expenditure were measured after stomach or bowel resections in patients receiving either hypercaloric or hypocaloric parenteral nutrition. The results were correlated with the availability of various blood proteins and amino acids as well as the concentration of different substrates of the intermediary metabolism. The results show that there is no need for a hypercaloric parenteral nutrition even after major abdominal surgery. Apart of a slightly better nitrogenbalance, which is, however, connected with an increased nitrogen impact on the organism there was no advantage over hypocaloric intravenous nutrition at least until the fifth day after the operation. PMID- 1943412 TI - [What is the role of nutrition in Crohn disease? A contribution to the importance of dietary therapy in regional enteritis]. AB - The clinical appearance of Crohn's disease (CD) is especially marked by nutritional deficits and insufficiencies. For a long time the goal of nutritional care was reduced to the readjustment of the nutritional status. The development and clinical use of controlled parenteral nutrition (TPN) and enteral nutritive solutions (EN) did not only emphasize this therapeutical issue, but furthermore showed positive effects on the conservative as well as on the surgical treatment concepts. Therefore today artificial nutritional support is a firm part of therapy in acute, active phases or in the contact of surgical management of CD. This is especially valid in children, where complications in general and growth failure in particular can be reduced. EN is the preferred feeding method in most of the cases, due to a lower complication rate and reduced cost when compared to TPN. The question regarding the importance of nutritional support as primary therapy has also been investigated. The results differ extensively, but point towards the conclusion that patients with solitary small bowel disease do profit from this therapeutical concept. Nevertheless it is unclear, how TPN or EN interfere in the pathophysiology or -biochemistry in this process. A question about reduction e.g. of allergic components of daily diet did stimulate new theories regarding the hypothesis of a possible causal relationship between diet and the pathogenesis of CD. Investigations on dietary habits and daily dietary therapy did not reveal an overall accepted dietary guideline. Nevertheless it seems obvious that dietary counselling has a positive effect on the disease process. It does appear, that today in the acute, active phase as well as in the long term management of Crohn's disease nutritional-care is an important therapeutical method. PMID- 1943413 TI - [Incidentaloma of the adrenal gland: when operate?]. PMID- 1943414 TI - Anatomical correlates of functional recovery in the avian inner ear following aminoglycoside ototoxicity. AB - Tucci and Rubel have demonstrated functional recovery of the chick cochlea following aminoglycoside ototoxicity. The cochleae of these same animals were examined by scanning electron microscopy (SEM) in order to further understand this recovery process. Hatchling chicks were given daily doses of gentamicin for 10 days. Auditory-evoked potential measurements and examination of the cochlea by scanning electron microscopy were performed after survival periods of 5 days to 20 weeks. After 5 days of gentamicin exposure, there was near complete basal hair cell loss associated with a high-frequency hearing loss. Apical progression of damage with a broad-band hearing loss occurred over 4 weeks. At 20-weeks, hair cell counts were normal with a small high-frequency hearing loss. Hair cell regeneration played a major role in the functional recovery of the cochlea. PMID- 1943415 TI - Repair of peripheral nerves of unequal diameters. AB - Four techniques for anastomosis were investigated for the anastomosis of a large proximal segment to a smaller distal segment of rat peripheral nerve with a size disparity of approximately 3 to 1. The techniques were perineural sutures (group I), KTP laser annealing (group II), collagen tubes with a 5-mm gap between the nerve segments (group III), and collagen tubes without a gap between the nerve ends (group IV). At 6 weeks there were no gross nerve distractions in groups I or IV. There were two failures in group II and three in group III. The percentage of fibers that crossed intact anastomoses were: group I, 89%; group II, 75%; group III, 115%; group IV, 125% (P less than .05 for the collagen tube repairs). Our results indicate that the suture technique is still the most reliable method of nerve repair. However, collagen tubes were effective in increasing the percentage of axons crossing the anastomosis. PMID- 1943416 TI - Revision stapes surgery. AB - With the decline in primary cases of otosclerosis surgery, revision stapes operations are becoming a higher percentage of otosclerosis practice. Are the results from revision stapes surgery today comparable with those of surgeons trained prior to the present decline? A retrospective review of 559 consecutive stapes operations performed by the author revealed 109 revision operations. A retrospective review of these cases reveals that the most common cause for revision surgery was displaced prostheses and incus necrosis. The hearing results are dependent on the surgical pathology. In this series, the airborne gap was closed to less than 10 dB in 58% of cases, there were 64% of cases of displaced prostheses, and 57% of cases of incus necrosis, which is comparable with previously reported studies. PMID- 1943417 TI - Soft-tissue complications of laser surgery for recurrent respiratory papillomatosis. AB - Twenty-two patients with recurrent respiratory papillomatosis underwent 105 carbon dioxide (CO2) laser microlaryngoscopic and tracheobronchoscopic operations from July 1986 through February 1990. All soft-tissue complications, whether intraoperative or delayed secondary to laser surgery, were retrospectively analyzed. The intraoperative laser-related soft-tissue complication rate was zero. Two of the 22 patients acquired slight unilateral true vocal cord scar tissue and 1 patient developed a small posterior laryngeal web. The delayed soft tissue complication rate was 13.6%, which compares favorably with published reports of 28.7% and 45%. This low complication rate has resulted from the selection of appropriate CO2 laser emission parameters and the use of the microspot micromanipulator, which help minimize lateral and/or deep thermal damage at the site of laser impact. PMID- 1943418 TI - Ototoxicity of furosemide during development. AB - The rat is an altricial animal which serves as a useful model for human auditory development. The purpose of the present study was to investigate the effects of furosemide on cochlear function and the stria vascularis ultrastructure at various postnatal ages. Rat pups anesthetized with ketamine hydrochloride/xylazine hydrochloride received furosemide 35 mg/kg intravenously (IV), and the endocochlear potential and compound action potential of the eighth nerve were recorded. The stria vascularis was removed and prepared for transmission electron microscopy. Rat pups 9 to 28 days of age had a much greater reduction of endocochlear potential and elevation of the compound action potential threshold than animals older than 30 days. These physiologic changes were accompanied by edema of the stria on transmission electron microscopy only in animals at susceptible ages. These findings support the concept of a critical period of susceptibility to ototoxic drugs during development and could have important clinical implications in premature infants. PMID- 1943419 TI - Surgical pathology of cancer of the oral cavity and oropharynx. AB - A study was designed to determine the influence of certain surgical pathologic findings on tumor spread and survival in patients with cancer of the oral cavity and oropharynx. All patients with the histopathological diagnosis of carcinoma of the oral cavity or oropharynx from 1955 to 1983 were included in the study. Using the Head and Neck Tumor Registry of the department of otolaryngology of the Washington University School of Medicine, information was obtained regarding preoperative evaluation, staging, classification, diagnosis, treatment, surgical pathology parameters, and outcome results. The patient populations consisted of 545 patients with oral cavity cancer and 224 patients with oropharynx cancer, all of whom were eligible for 3-year follow-up. Information from a retrospective analysis of the pretreatment examination records regarding site and size of the primary tumor and neck dissection, and specific treatment, and from surgical pathology reports regarding site, size, tumor spread and resection margins, was correlated with treatment outcome. The database file was analyzed using dbase III and its companion program Framework, and SAS PC (Statistical Analysis Systems for personal computers). PMID- 1943420 TI - The rhinologic evaluation of Alzheimer's disease. AB - Olfactory dysfunction is currently not listed among the NINCDS-ADRDA clinical criteria for the diagnosis of Alzheimer's disease. There is a large amount of psychophysical and neuropathologic evidence to suggest that patients with Alzheimer's type dementia have olfactory system abnormalities. The rhinologic status of this group has not been characterized. The authors examined 21 Alzheimer's patients and 21 age-matched controls to determine whether 1. the Alzheimer's group, in fact, had a diminished sense of smell, and whether 2. rhinologic factors were responsible for this nasal dysfunction. The findings support a neurologically mediated phenomenon as the cause for significant impairment in olfactory function in patients with probable Alzheimer's disease. PMID- 1943421 TI - Study of the normal and insufficient velopharyngeal valve by the "Forced Sucking Test". AB - A thorough assessment of the velopharyngeal (VP) closure dynamics is important for therapeutic planning in patients with nasal speech. An additional diagnostic tool to the standard endoscopic examination of the VP valve, the "Forced Sucking Test" (FST) is presented. In this study, 110 patients with a normal VP valve and 40 patients with VP insufficiency were subjected to a comprehensive endoscopic examination. When existent, Passavant's ridge clearly appears in 80% of these cases during the FST. This is advantageous, since the ridge is often unseen during routine nasendoscopy. Passavant's ridge appears indistinguishable in shape and level during speech and FST. During FST, the bulge of the uvular ridge is clearly seen on the flat or concave nasal surface of the velum. In cases of diastasis of the velar musculature, the midline V-defect of the velum is clearly seen. The test is particularly important in children with concomitant adenoid hypertrophy. The findings are discussed in terms of their implications for the anatomy and physiology of the VP valve. FST is recommended as an additional and complementary part of the endoscopic examination of the VP valve. PMID- 1943422 TI - One-eye and locomotor compensation in guinea pigs. AB - This study was carried out to examine the effect of blindfolding one eye on locomotor compensation after unilateral labyrinthectomy in guinea pigs. A platform runway, designed to examine the locomotion of this species of animals, was used. Eighteen Hartley-strain albino guinea pigs were used. These animals were divided into three groups, with seven in the control group, six whose right eye had been surgically closed in another group, and five whose left eye had been surgically closed in yet another group. After 7 to 11 days of training, a chemical labyrinthectomy by chloroform injection into the middle ear was performed under light ether anesthesia. Animals were checked for locomotion daily by the aforementioned platform method for about a week until regaining preprocedure levels. The locomotor compensation, depicted through the decrement of the deviation count and running time, was observed. Results have shown that the animal's locomotor compensation retarded significantly in the one-eye groups compared to the control group. In addition, those animals whose one eye, ipsilateral to the labyrinthectomy side, was closed required significantly longer time to resume the preprocedure running performance level than the animals whose one eye, contralateral to the lesion side, was closed. Thus, during locomotor compensation, the visual input obtained by animals with one eye ipsilateral to the labyrinthectomy side may be important compared to the visual input of the animals with the contralateral eye. PMID- 1943423 TI - Treatment of oromandibular dystonia with botulinum toxin. AB - Botulinum toxin produces muscle weakness by inhibition of acetylcholine release at the neuromuscular junction. The toxin has been used successfully for symptomatic treatment of focal dystonias. Our experience in the use of botulinum toxin for the treatment of oromandibular dystonia in five patients is reported. Improvement following treatment was reported as marked by 1 patient, moderate by 1 patient, and mild by 3 patients. Similar improvement was noted by the examiners. One patient with mild cosmetic improvement developed significant dysphagia requiring feeding by a nasogastric tube for a 3-month period. PMID- 1943424 TI - "Split" full-thickness skin grafts. PMID- 1943425 TI - Endoscopic ENT photography: a comparison of pictures by standard color films and newer color video printers. PMID- 1943426 TI - Upper lid blepharoplasty: skin flap vs. pinch. PMID- 1943427 TI - Platysma myocutaneous flap: caveats reexamined. PMID- 1943428 TI - Intracranial complications of sinusitis. PMID- 1943429 TI - [Ulcer of the stomach and duodenum: enormous change in diagnosis and therapy]. PMID- 1943430 TI - [Traveler's diarrhea. Incidence--pathogens--pathophysiology--clinical aspects- prevention and therapy]. AB - About one-third of travellers will be affected by travellers' diarrhoea. Regions with low risk are Northern Europe, the United States, Australia and New Zealand. Intermediate risk is found in Southern Europe, most islands of the Caribbean, Japan, Israel and Southern Africa and high risk in developing countries. Among the most commonly isolated pathogens are enterotoxigenic E. coli, Salmonella, Shigella, Campylobacter, G. lamblia, E. histolytica and viruses. The individual risk depends on the age and constitution of the traveller, on styles of travel and on previous expositure in developing countries. Travellers' diarrhoea is usually a short self-limited disease for 2-5 days. Nutritional prophylaxis along the principle "boil it, cook it, peel it, or forget it" is useful. Prophylaxis with non-antibiotic drugs is only justified in special cases. PMID- 1943431 TI - [Lymph follicle formation and development of intestinal metaplasia in antrum mucosa as a reaction to Helicobacter pylori infection]. AB - We examined 171 patients (76 females and 95 males) with definite type B Gastritis. Antrum specimens were taken from all participants for histological examination. We studied the correlations between the formation of lymphoid follicles, the severity of gastritis, the degree of activity of gastritis and the density of Helicobacter pylori colonization. In addition we noted the distribution and extent of the intestinal metaplasia. In patients with high degree HP-colonization we found formation of lymphoid follicles in 59.8%, in patients with low degree HP-colonization in 35% and in patients without colonization only in 10.2% (high degree vs. low degree colonization p less than 0.05, low degree vs. absent colonization p less than 0.025, high degree vs. absent colonization p less than 0.0005). In patients with high grade type B Gastritis we detected formation of lymphoid folliclesin 58%. There was no case of formation of lymphoid follicles in patients with low grade type B-Gastritis. Patients with a high grade activity of the type B-Gastritis displayed a formation of lymphoid follicles in a higher percentage as patients with a low grade activity of the gastritis (66% vs. 33%, p less than 0.0005). In the antrum intestinal metaplasia of the types I and II could be found significantly more frequent in patients with high grade Type B-Gastritis than in patients with low grade Type B-Gastritis (34.1% vs. 8.8%, p less than 0.005). Intestinal metaplasia was found more frequently in connection with high and low activity of type B Gastritis than without activity (p less than 0.005 and p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943432 TI - [A rare combination of two autoimmune diseases (scleroderma, primary biliary cirrhosis) in relation to parietal cell antibodies]. AB - Case report of combined progressive sclerosis and primary biliary cirrhosis added to a chronical atrophic gastritis in the beginning. Diagnosis of one autoimmune disease should prompt a search for further associated autoimmune affections to care before there is a grave disease--if this is possible. PMID- 1943433 TI - [Jejunal diverticulosis--a rare cause of gastrointestinal hemorrhage]. AB - We report a case of gastro-intestinal bleeding caused by jejunal diverticulosis, in which preoperative diagnosis could be achieved by selective angiography. Even though the small bowel is a rare localisation of bleeding (1% of all cases), this part of intestine should be included into diagnostic considerations. Jejunal diverticulosis only requires operative treatment after occurrence of complications, small bowel resection is regarded as treatment of choice in these cases. PMID- 1943434 TI - Rebound cue state following a single dose of haloperidol. AB - It has been reported that chronic administration of haloperidol produces an amphetamine-like rebound cue state. The experiments reported here were designed to assess whether a similar rebound phenomenon would result from a single dose of haloperidol. Rats were trained to discriminate .5 mg/kg amphetamine from distilled water. Five groups were formed to allow testing of haloperidol's effect at 12, 18, 24, 30, and 36 hr postinjection. Each animal was given 0, .5, 1.0, and 1.5 mg/kg haloperidol at its appropriate injection time in a counterbalanced fashion with one week between each test. A shift in the dose-response function of amphetamine that occurred during these weeks, however, precluded appropriate analysis of haloperidol's effects. Given this result, a second experiment was conducted using a between-subjects design. Half of the animals were injected with 1 mg/kg haloperidol 23 hr prior to testing, whereas the others were injected with distilled water. When tested, the haloperidol group responded 33% of the time on the amphetamine-correct lever, whereas the control group responded at 20%. The observation of posthaloperidol rebound in the between-subjects study and the failure to find significant temporal patterns of rebound phenomena using a within subjects design have both theoretical and methodological importance. PMID- 1943435 TI - Acute ethanol treatment induces a bimodal response of phospholipid acylation rates in rat red blood cells. AB - A single intraperitoneal injection of ethanol (4 g/kg) in rats elicited a bimodal response of acylation rates in phosphatidylcholine and phosphatidylethanolamine of intact red blood cells. Within an initial period, ethanol inhibited acylation rates. The inhibition then reversed, leading to increased values which persisted as long as ethanol was present in plasma. Acylation rates were not correlated to ethanol concentrations in plasma. We suggest that red cells first desensitize to, then overcompensate for the inhibitory effect of ethanol on acylation reactions. These adaptive changes may be one of the events mediating membrane tolerance to ethanol. PMID- 1943436 TI - Studies on the antimalarial mode of action of quinoline-containing drugs: time dependence and irreversibility of drug action, and interactions with compounds that alter the function of the parasite's food vacuole. AB - The quinoline-containing antimalarial drugs chloroquine, quinine and mefloquine exert an irreversible inhibitory effect on erythrocytic stages of Plasmodium falciparum grown in culture. Inhibition is time- and concentration-dependent and the full effect is observed after 2-6 hours of exposure to the drug. Washing of infected cells after drug exposure in the presence of NH4Cl to accelerate drug efflux, intensifies the inhibitory effect of chloroquine, probably due to the pH dependent release of highly concentrated drug from the acidic food vacuole of the parasite. When both antimalarials and NH4Cl are present in the culture, drug effect is reduced, as expected from the demonstrable alkalinization of the food vacuole and the consequent reduction in drug accumulation. The protease inhibitor leupeptin inhibits digestion of ingested host cell cytosol, and thus inhibits parasite growth, though reversibly so (Rosenthal et al, J. Clin. Invest. 82 1560 1566 (1988)). Thus, although the antimalarials also inhibit the feeding process, this is not the cause of their irreversible action. Leupeptin is found to be antagonistic to antimalarials' action, suggesting that the drugs form complexes with products of host cell digestion that are responsible for irreversible inhibition of parasite growth. PMID- 1943437 TI - Antineoplastic ether-linked phospholipid induces differentiation of acute myelogenous leukemic KG-1 cells into macrophage-like cells. AB - The culture of a human acute myelogenous leukemic cell line (KG-1) with a synthetic ether-linked phospholipid: 1-0-octadecyl-2-0-methylglycerol phosphocholine (ET-18-OCH3), suppressed the growth of the KG-1 cells while the variant subline, (KG-1a cells) similarly treated was unresponsive. The growth inhibition of the KG-1 cells was accompanied by morphological changes into cells of the monocyte/macrophage lineage. Histochemically, the ET-18-OCH3-treated KG-1 cells increase 17-fold in the nonspecific esterase activity when compared to control non-treated cells, whereas they responded negatively in the assay for the reduction of soluble nitroblue tetrazolium into insoluble blue formazan deposits (a marker for cells of the granulocytic lineage). Taken together, our data revealed that the synthetic ether-lipid inhibited the growth of the KG-1 acute myelogenous leukemic cells while inducing the differentiation of these cells into cells of the monocyte/macrophage-lineage. These effects of the synthetic ether lipid raise the possibility that naturally occurring ether-linked phospholipids may likewise function in vivo to modulate hyperproliferative processes and thus warrant further explorations. PMID- 1943438 TI - Acute and long-term amphetamine treatments alter extracellular ascorbate in neostriatum but not nucleus accumbens of freely moving rats. AB - The ability of amphetamine to alter the extracellular level of ascorbate, an apparent modulator of neostriatal function, was assessed voltammetrically in the neostriatum and nucleus accumbens of awake, behaving rats. Whereas acute administration (1.0 and 5.0 mg/kg d-amphetamine) produced a dose-dependent rise in neostriatal ascorbate, there was no change in the nucleus accumbens. Vehicle injections had no significant effect on ascorbate levels in either location. Administration of 5.0 mg/kg d-amphetamine for one week enhanced neostriatal ascorbate release even further, but this effect returned to acute levels when treatment continued for a second week. Multiple amphetamine injections for up to two weeks failed to alter extracellular ascorbate in the nucleus accumbens. The results of these experiments confirm a site-specific action of amphetamine on ascorbate release and suggest complex changes in the extracellular level of this substance in the neostriatum with long-term treatment. PMID- 1943439 TI - Interaction of aluminum ions with phosphoinositide metabolism in rat cerebral cortical membranes. AB - Aluminum (Al) is believed to exert a primary role in the neurotoxicity associated with dialysis encephalopathy and has been suggested to be involved in a number of other neurological disorders, including Alzheimer's disease. Al, complexed with fluoride to form fluoroaluminate (AlF4-), can activate the GTP-binding (G) proteins of the adenylate cyclase and retinal cyclic GMP phosphodiesterase systems. Since an involvement of G-proteins with cerebral phosphoinositide (PtdIns) metabolism has also been suggested, in this study we investigated the interaction of the stable GTP analogue GTP(S), Al salts and NaF with this system. In rat cerebral cortical membranes, GTP(S) dose-dependently stimulated [3H]inositol phosphates ([3H]InsPs) accumulation. This effect was potentiated by carbachol and was partially prevented by the GTP-binding antagonist GDP(S), indicating that CNS muscarinic receptor activation is coupled to PtdIns hydrolysis via putative G-protein(s). GTP(S) stimulation was also inhibited by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, which is known to exert a negative feedback control on agonist-stimulated PtdIns metabolism. Both Al salts and NaF mimicked the action of GTP(S) in stimulating PtdIns turnover. Their actions were highly synergistic, suggesting that AlF4- could be the active stimulatory species. However, the stimulatory effects of AlCl3 and/or NaF were not potentiated by carbachol and were not inhibited by GDP(S) and PMA, suggesting that separate sites of action might exist for GTP(S) and AlF4-. In the nervous tissue, activation of PtdIns hydrolysis by Al (probably as AlF4-) may be mediated by activating a regulatory G-protein at a location distinct from the GTP-binding site or by a direct stimulation of phospholipase C. PMID- 1943440 TI - Splenocyte subsets in normal and protein malnourished mice after long-term exposure to cocaine or morphine. AB - An experimental model which resembles human drug addiction was developed to study the effect of chronic drug (cocaine or morphine) administration on the immune system. As malnutrition has been associated with drug use, a low protein diet has been evaluated for its contribution to the impairment of the immune system during cocaine/morphine addiction. Female C57BL/6 mice that received a 20% or 4% casein diet were studied. Both drugs were administered intraperitoneally daily for 11 weeks and drugs were administered in increasing daily doses, beginning after 3 weeks of diet consumption. Doses of cocaine began with 5 mg/kg body weight and reached the maximum dose of 40 mg/kg/day at the fourth week. Doses of morphine gradually increased from 10 mg/kg to 75 mg/kg body weight with the maximum dose reached after 5 weeks of treatment. Cocaine administration reduced body weight, particularly in the low protein diet group, and spleen weight in protein malnourished mice. Cocaine as well as saline injected mice showed a decrease in the percentage of CD4+ CD8+ and Mac-1+ cells and an increase in B cells in the spleens of well nourished mice. Morphine-treated mice showed similar results to those observed in cocaine or saline treated mice. These results suggest that cocaine, morphine or saline injection can alter the percentage of cells that express a defined phenotype independently of the nutritional status of the subject. Moreover, the effect appears dependent on a stress mediated process. PMID- 1943441 TI - Induction of hepatocyte mitosis in intact adult rat by interleukin-1 alpha and interleukin-6. AB - In the adult rat the liver is normally quiescent, but it proliferates rapidly in response to partial hepatectomy (PH). A hepatectomized rat is subjected to stress by the operation. We have examined the effects of acute phase cytokines. To investigate the mediation of hepatocyte growth, recombinant human interleukin-1 alpha (IL-1) and interleukin-6 (IL-6) were injected into male rats. Administration of IL-1 or IL-6 followed by NH4Cl and glucagon could induce hepatocyte mitosis 30 h after the first injection. This activity was lost when interleukins were exposed to 90 degrees C for 30 minutes. NH4Cl augmented the effects of IL-1 and IL-6. These results suggest that the IL-1 and IL-6 are important mediators of liver regeneration after PH. We present a hypothesis for the triggering mechanism of hepatocyte proliferation. PMID- 1943442 TI - Induction of the ATP-dependent proteolytic system in guinea pig reticulocyte lysates by triiodothyronine. AB - The mechanism involved in the decreased numbers of several trans-membrane proteins such as sodium pump sites, sodium-lithium countertransport, sodium potassium cotransport proteins, proteins mediating the passive efflux of sodium and insulin receptors in erythrocytes from patients with hyperthyroidism is not known. The ATP-dependent proteolytic system which is involved in the loss of trans-membrane proteins during the maturation of the reticulocyte may be involved in the accelerated loss of these membrane proteins. Therefore, the effect of thyroid hormones on the ATP-dependent proteolytic activity of reticulocyte lysates was examined in this study. Reticulocytosis was induced in 14 guinea pigs by phenylhydrazine hydrochloride injections for 5 consecutive days followed by 2 days of rest. T3 (10 micrograms/100 g body weight) was injected into 7 animals on day 4 and day 6. Reticulocyte-rich blood was withdrawn on day 8. Oxygen consumption determined 24 hours after injection of T3 was 25% higher (p less than 0.01) and T3 treated animals had a 2.5 fold higher (p less than 0.01) weight loss than control animals. The ATP-dependent proteolytic activity measured in reticulocyte lysates using 125I labelled lysozyme was 3.6 fold higher in the T3 than in the control group of guinea pigs (p less than 0.01). We conclude that thyroid hormones induce the ATP-dependent proteolytic activity of reticulocyte lysates which may be responsible for the reduced number of several trans-membrane proteins found in erythrocytes from patients with hyperthyroidism. PMID- 1943443 TI - Stimulatory action of calcium L-threonate on ascorbic acid uptake by a human T lymphoma cell line. AB - The effects of preincubation of human T-lymphoma cells with increasing concentrations of calcium L-threonate on the uptake of L-[1-14C]ascorbic acid were examined. Calcium L-threonate (0-1,000 mg%) stimulated ascorbic acid (1.25 mg%) uptake in a dose-dependent manner. These results indicate that calcium threonate and possibly other ascorbic acid metabolites have biological activity and potential pharmacological applications. PMID- 1943444 TI - Failure of prostacyclin, beta-carotene, atropine and cimetidine to produce gastric cyto- and general mucosal protection in surgically vagotomized rats. AB - Different chemicals (such as ethanol, HCl, drugs) produce gastric mucosal injury. A special type of gastric mucosal defense, which differed from the inhibition of gastric acid secretion, was discovered in response to small doses of prostaglandins. This phenomenon was termed "gastric cytoprotection". Later, the existence of gastric cytoprotection was proved using different compounds, such as vitamin A and other carotenoids, prostacyclin, small doses of anticholinergic and H2-blocking agents. These compounds produce cyto-protection by different mechanisms. In this study we tested the role of vagus nerve on the development of these different types of gastric cytoprotection. These compounds prevent ethanol induced gastric mucosal injury in rats with intact vagus nerve, but their cyto- and mucosal protective effects disappear in surgically vagotomized rats. These results indicate that the intact vagus nerve is basically necessary for the overproduction of HCl and pepsin secretion, and for the development of gastric cytoprotection, produced by different compounds (e.g. prostacyclin, beta carotene, small doses of atropine and cimetidine) acting without the presence of inhibition of gastric acid secretion. PMID- 1943445 TI - Impact of ether anesthesia on the hypophyseal content of oxytocin neurophysin I and II: a comparative study with ketamine in the rat. AB - The effect of anesthetic stress on the major hormones of the posterior pituitary (PP), such as oxytocin (OT), oxytocin-neurophysin (OTNP-I) and its metabolic product, OTNP-II, was studied. Rats were treated with either a combination of atropine (0.87 mg/kg) and diphenylhydantoin (85 mg/kg) and then anesthetized with ketamine (42 mg/kg) or were directly anesthetized with diethyl-ether, and then killed. Controls were killed with a laboratory guillotine. Our study revealed that 1.) animals killed with a guillotine or being medicated with our drug combination prior to sacrifice had similar concentrations of OT, OTNP-I and OTNP II per PP and ml of blood; 2.) animals anesthetized with either prior to sacrifice had a decreased concentration of neuropeptides per PP; the blood concentration of OT was 1.6 times higher than in animals treated with the drug combination or killed directly with a guillotine. In addition plasma concentrations of OTNP-I and OTNP-II were above the baseline. We conclude that ether is not an adequate anesthetic for studying the neurophysins from the PP in vivo. Treatment of animals with atropine and diphenylhydantoin in combination with ketamine does not alter the profile of the major hormones from the PP during anesthetic stress. PMID- 1943446 TI - Pain perception in decapitated rat brain. AB - The question of humaneness of decapitation per se has been considered. The time required for the oxygen tension in decapitated rat brain to decline to a level at which the brain becomes unconscious was estimated to be 2.7 sec. Assuming that decapitation is a powerful arousal stimulus and that the resulting EEG activation (low voltage, fast activity) indicates a conscious awareness of pain and distress the maximum time the pain and distress could be perceived would be 2.7 sec. Hence, decapitation of rats per se may be considered humane. PMID- 1943447 TI - The effect of cyclophosphamide and gamma irradiation on adenosine deaminase and purine nucleoside phosphorylase in mice. AB - Changes in ADA and PNP activities in the spleens and thymuses of mice were studied after a single administration of cyclophosphamide (CY, 200 mg/kg) and after whole-body gamma irradiation (5.5 Gy), applied alone or three days after CY application. In the first days after the treatment the enzyme activities were significantly depressed (p less than 0.01) with the exception of ADA in the spleen, where a high elevation (220-380%) in relation to controls was observed. During the regeneration period a pronounced rise of PNP activity in the spleen occurred mainly after a combined application of CY and irradiation (270%). In the thymus the regeneration was manifested by a mild increase of both ADA and PNP activities towards control values. The findings suggest that the expressive changes of ADA and PNP activities, participating in the purine salvage pathway, may, after a cytotoxic treatment, influence the nucleotide pool and DNA synthesis in lymphoid organs. PMID- 1943448 TI - Dexamethasone induces biphasic effect on morphine hypermotility in mice: a dose related phenomenon. AB - The present study examined interaction between dexamethasone (DEX) and morphine on the locomotor activity in groups of mice by using the activity cage test. Morphine administration (30-75-150 mg/kg, ip) induced a dose-related increase of the locomotor activity of mice, whereas DEX per se (0.1-1.0-10 mg/kg, ip) did not modify the activity of control mice. Pretreatment of mice with DEX 0.1 mg did not alter the hyperactivity produced by the three doses of morphine. In contrast, DEX administered at 1.0 mg reduced the morphine effects on locomotor activity, whereas DEX at 10 mg potentiated the morphine hypermotility. Our results suggest that DEX may play an important regulatory role on the central effects of morphine through a differential modulation of brain excitability systems. PMID- 1943449 TI - Corticotropin releasing factor stimulates growth hormone secretion in neonatal rats. AB - Corticotropin releasing factor (CRF) both stimulates ACTH secretion from the pituitary and inhibits secretion of growth hormone (GH) in adult rats through actions in the CNS. The purpose of the present study was to evaluate these pituitary and central actions of CRF in neonatal rats, in which the hypothalamo- pituitary adrenal (HPA) axis is relatively hypo-functional. The results of this study show that central or peripheral administration of CRF evokes a marked dose related rise in serum corticosterone in 6-day old rats. The same doses of CRF stimulate, rather than inhibit GH secretion. These results suggest that CRF has unique central actions early in ontogeny. PMID- 1943450 TI - Physiological and pharmacological properties of adenosine: therapeutic implications. AB - Adenosine is a nucleoside which has been shown to participate in the regulation of physiological activity in a variety of mammalian tissues, and has been recognized as a homeostatic neuromodulator. It exerts its actions via membrane bound receptors which have been characterized using biochemical, electrophysiological and radioligand binding techniques. Adenosine has been implicated in the pharmacological actions of several classes of drugs. A number of studies strongly suggest that the nucleoside may regulate cellular activity in many pathological disorders and, in that respect, adenosine derivatives appear as promising candidates for the development of new therapeutic compounds, such as anticonvulsant, anti-ischemic, analgesic and neuroprotective agents. PMID- 1943451 TI - Effects of prenatal and postnatal exposure to vitamin A on the development of the murine immune system. AB - Vitamin A and its derivatives are known to enhance the immune system and affect embryogenesis. In this study, five daily subcutaneous injections of retinol palmitate (0.001 mg/kg body weight) were administered to eight female SW mice before mating. Six more weekly injections of retinol palmitate were given during pregnancy and lactation. Eight controls were similarly treated with saline. Four of the eight vitamin-A-treated females had litters, whereas seven of the eight saline-treated females had litters. Resultant litters did not differ in size or appearance. At 12 weeks of age, serum IgM and IgG1 levels were significantly higher in the progeny of vitamin-A-treated mothers before but not after immunization with a test antigen, sheep red blood cells (SRBC). This difference was not seen when other progeny were tested at the age of one year. Anti-SRBC titers did not differ in the two groups of progeny at the age of 12 weeks or one year. One-year-old progeny of vitamin-A-treated mothers weighed significantly more than did control progeny; significant enlargement of the heart, spleen, and kidneys was observed. However, organ-to-body-weight ratios did not differ significantly. In a separate experiment, adult female mice treated with varying doses of vitamin A (five daily doses of 0.0001, 0.0005, or 0.001 mg/kg body weight) showed a dose-dependent reduction of serum IgG1 and hematocrits, but no change in serum IgM levels or leukocyte counts. Resting untreated mice had IgM levels which were one-half those seen in saline-treated controls. These studies indicate that large doses of vitamin A can affect some aspects of the developing and mature murine immune system. PMID- 1943452 TI - Angiotensin receptor subtypes in rat, rabbit and monkey tissues: relative distribution and species dependency. AB - The displacement of [125I]Sar1, Ile8 angiotensin II binding by the receptor subtype selective angiotensin II antagonists, DuP-753 and WL-19 (PD121981) was used to define the relative proportion of angiotensin subtype AT1 and subtype AT2 receptors, respectively in various tissues (aorta, heart, adrenal cortex, kidney cortex and brain) of the rat, rabbit and monkey. The relative abundance of these receptor subtypes varied greatly not only among different tissues of the same species but also within the same tissue of different species. The relative affinity of the DuP-753 and WL-19 for the angiotensin receptor subtypes did not vary markedly suggesting that the two angiotensin receptor subtypes in these tissues and species are similar. PMID- 1943453 TI - Robust growth hormone (GH) secretion in aged female rats co-administered GH releasing hexapeptide (GHRP-6) and GH-releasing hormone (GHRH). AB - Aging is associated with a blunted growth hormone (GH) secretory response to GH releasing hormone (GHRH), in vivo. The objective of the present study was to assess the effects of aging on the GH secretory response to GH-releasing hexapeptide (GHRP-6), a synthetic GH secretagogue. GHRP-6 (30 micrograms/kg) was administered alone or in combination with GHRH (2 micrograms/kg) to anesthetized female Fischer 344 rats, 3 or 19 months of age. The peptides were co-administered to determine the effect of aging upon the potentiating effect of GHRP-6 on GHRH activity. The increase in plasma GH as a function of time following administration of GHRP-6 was lower (p less than 0.001) in old rats than in young rats; whereas the increase in plasma GH secretion as a function of time following co-administration of GHRP-6 and GHRH was higher (p less than 0.001) in old rats than in young rats (mean Cmax = 8539 +/- 790.6 micrograms/l vs. 2970 +/- 866 micrograms/l, respectively; p less than 0.01). Since pituitary GH concentrations in old rats were lower than in young rats (257.0 +/- 59.8 micrograms/mg wet wt. vs. 639.7 +/- 149.2 micrograms/mg wet wt., respectively; p less than 0.03), the results suggested that GH functional reserve in old female rats was not linked to pituitary GH concentration. The differential responses of old rats to individually administered and co-administered GHRP-6 are important because they demonstrate that robust and immediate GH secretion can occur in old rats that are appropriately stimulated. The data further suggest that the cellular processes subserving GH secretion are intact in old rats, and that age-related decrements in GH secretion result from inadequate stimulation, rather than to maladaptive changes in the mechanism of GH release. PMID- 1943454 TI - The binding of SCH 39166 and SCH 23390 to 5-HT1C receptors in porcine choroid plexus. AB - SCH 39166 is a novel benzonaphthazepine, which has been characterized as a potent and selective D1 antagonist. Recently, its D1 selective benzazepine predecessor, SCH 23390, has been shown to bind to 5-HT1C binding sites in the choroid plexus. Therefore, the present studies were undertaken to determine if SCH 39166 has any measurable affinity for 5-HT1C binding sites. Our results indicate that SCH 39166 exhibited poor affinity for the 5-HT1C receptor, with a Ki of 1327 nM. In contrast, SCH 23390 inhibited [3H]-mesulergine binding to 5-HT1C receptors with a Ki of 30 nM. The non-selective 5-HT antagonist, methysergide, inhibited binding with a Ki of 2.4 nM. Finally, studies with the stereoisomers of SCH 39166 and SCH 23390 demonstrated that stereoselectivity at the 5-HT1C site is significantly less than for the D1 site. PMID- 1943455 TI - Calcitonin gene-related peptide increases the production of glycosaminoglycans but not of collagen type I and III in cultures of rat fat-storing cells. AB - We investigated whether calcitonin gene-related peptide (CGRP) was able to affect the production of collagen and glycosaminoglycans (GAG) in cultures of rat fat storing cells (FSC). Rat CGRP (1 nM-1 microM) induced a dose-dependent increase of total GAG production in FSC cultures with an EC50 of 28 nM. One uM human CGRP (8-37) shifted the dose-response curve of rat CGRP to the right (EC50 = 257 nM) without depressing the maximal response. Salmon calcitonin (1 nM-1 microM) did not significantly modify total GAG accumulation in FSC cultures. Collagen type I and III production was not significantly affected by either CGRP or calcitonin in FSC cultures. These findings suggest that peripheral sensory neuropeptides may modulate liver fibrogenesis. PMID- 1943456 TI - Cellular binding proteins of thyroid hormones. AB - Cellular binding proteins of thyroid hormones are present in the cell nucleus, cytosol, cell membrane, and mitochondria. While nuclear binding is proven to mediate hormone action, the exact roles of the other binding sites remain to be established. Nuclear receptor associates with DNA, core histone, and nuclear matrix and preferentially distributes in transcriptionally active chromatin due to interaction with H1 histone. Of particular importance is the binding of nuclear receptor to specific DNA sequences of target genes, termed thyroid responsive elements. The binding is stabilized by non-receptor nuclear protein. Upon binding thyroid hormone, nuclear receptor is activated through alterations in the steric configuration, leading to changes in the rate of transcription of the target genes. Multiple nuclear receptor forms exist with likely distinct functional roles. Cytosolic thyroid hormone binding proteins are also heterogeneous. One form is under the control of cell metabolism (NADP and NADPH) and it may have a role in transport of the hormone to mitochondria and nucleus. Membrane-linked thyroid hormone binding proteins may have dual functional roles: one is to mediate hormone action and the other is to support active uptake of hormones by cells. Mitochondrial function may be regulated by thyroid hormone through mitochondrial binding sites in cooperation with nuclear receptor-mediated pathway. Further studies are required to elucidate the exact functional roles of non nuclear thyroid hormone binding proteins. PMID- 1943457 TI - Vitamin and micronutrient concentrations in cyclosporine-induced renal tumor from diabetic rats. AB - Concentrations of vitamins, biopterin, free inositol and acid-soluble carnitine were determined in cyclosporine A induced renal adenocarcinoma and uninvaded renal tissue from streptozotocin diabetic rats. Vitamin B6, thiamin, riboflavin, nicotinate, free inositol and acid-soluble carnitine were significantly decreased in tumor than nontumor tissue. Concentrations of folic acid, B12, biotin, pantothenate and biopterin were similar in both tissues. These studies suggest that renal adenocarcinoma affects concentrations of only certain vitamins and micronutrients. PMID- 1943458 TI - The mechanical and electrical effects of rhinoceros viper (Bitis nasicornis) venom on the isolated perfused guinea pig heart and atrial preparations. AB - The mechanical and electrical effects of the venom of Bitis nasicornis were studied on the guinea-pig Langendorff and left atrial myocardium preparations. While Langendorff preparations were treated with individual doses of 0.1, 0.6 and 1.4 mg, isolated left atria were treated using concentrations of 2.0, 20 and 200 micrograms/ml of venom in the perfusion solution. In the Langendorff preparation, transient increases in left ventricular systolic pressure (LVSP) and heart rate (HR) were seen after 0.1 mg of venom. When 0.6 mg of venom was given, the increases were followed by decreases, while 1.4 mg doses simply induced decreases in LVSP and HR. After both 0.6 and 1.4 mg doses the decreases were accompanied by increases in left ventricular diastolic pressure. In addition to these mechanical effects, transient increases in HR with atrio-ventricular blocks, ventricular extrasystoles and tachycardia were observed after each dose. In the left atrium the 2 micrograms/ml venom concentration produced an increase, followed by a decrease, in the maximum tension developed, which was only seen to decrease with higher concentrations of 20 and 200 micrograms/ml of venom. A dose dependent significant reduction in the action potential duration was observed for the doses of 0.6 and 1.4 mg in the ventricle and for all three concentrations in the atrium. PMID- 1943459 TI - In vitro biosynthesis of rat sperm outer dense fiber components. AB - Conditions were established for in vitro culture of seminiferous tubules of adult rat testis. Tubules fragments were able to incorporate radioactive amino acids for up to 6 hours of incubation at 32 degrees C in a modified Eagle's minimum media, indicating biosynthetic activity. Addition of D-glucose (11 Mm) increased the incorporation of either [3H] Leucine or [35S] Methionine four-fold in the protein components of seminiferous tubules. Polyclonal antibodies against outer dense fibers (ODF) polypeptides, which represent approximately 30% of the total sperm proteins, immunoprecipitated 5% of the total radioactivity from cultures carried out either in the presence or absence of D-glucose. Moreover, antibodies specific for the 27-30 kilodalton polypeptides of ODF immunoprecipitated 2% of the total radioactivity, showing no differences in the presence and absence of D glucose. This study indicates that ODF polypeptides can be synthesized in vitro at 32 degrees C with and without D-glucose. PMID- 1943460 TI - Action of amyloid beta-protein on protein kinase C activity. AB - Amyloid beta-protein (A beta), the major protein of cerebrovascular and plaque amyloid in Alzheimer disease, is considered a primary factor in the pathology of this disease. The effect of synthetic A beta (1-40) on the activity of protein kinase C (PKC) was studied with histones for a substrate in a mixed micellar assay, and with calmodulin-depleted soluble brain proteins in a liposomal system. We report here that A beta affects PKC activity in a biphasic manner. An initial stimulation of PKC was noted at low concentrations of A beta (less than 2.5 microM); while PKC-inhibition was observed in a concentration-dependent manner at higher concentrations of A beta. The in vitro phosphorylation of 20, 47, and 87 kDa brain proteins (known PKC substrates) was significantly reduced by 60 microM A beta. The role of 20 kDa in memory storage, of 87 kDa in neurotransmission and neurosecretory processes, and of 47 kDa in long-term potentiation or memory is well recognized, and A beta is known to have both neurotrophic and neurotoxic effects. Since PKC plays an important role in neuronal function, it is suggested that dual modulation of PKC by A beta may be linked to its neurotrophic and neurotoxic effects. We propose that at low concentrations A beta, by stimulating PKC, may contribute to neurites generation; and at higher concentrations A beta, by inhibiting PKC activity, might lead first to memory impairment, and then to neuronal loss. PMID- 1943461 TI - CGS 15943, a nonxanthine adenosine receptor antagonist: effects on locomotor activity of nontolerant and caffeine-tolerant rats. AB - CGS 15943 (0.1-10 mg/kg, IP) dose-dependently increased the locomotor activity of rats to the same extent as caffeine (1.0-100 mg/kg, IP) did and was approximately 26 times more potent than caffeine. N-Ethylcarboxamidoadenosine (0.001-0.01 mg/kg, SC), an analog of adenosine, dose-dependently decreased locomotor activity; this effect was antagonized surmountably by concurrent administration of CGS 15943. The apparent pA2 value for this interaction, 6.57, was approximately 1.5 log-units (28-fold) higher than the pA2 for caffeine-NECA reported previously. Rats consuming 70 mg/kg/day of caffeine via their drinking water were tolerant to the stimulation of locomotor activity induced by both caffeine and CGS 15943. These results suggest that caffeine and CGS 15943 increase locomotor activity by a common mechanism of action possibly involving adenosine receptors or a cellular element conformationally similar to adenosine receptors. PMID- 1943462 TI - Influence of stress on the maturity of T-cells. AB - Stress is known to influence the immune function via an effect on the central nervous system. We previously presented data showing that stress alters the population of T-cell subsets in mice. The variations of T-cell subsets in the thymus, peripheral blood, and spleen in mice similarly stressed by immobilization or by unavoidable and opioid-dependent stress were measured by flow cytometry using the monoclonal antibodies anti-L3T4, anti-Lyt 1, anti-Lyt 2 and anti-Thy 1, 2. Immobilization stress was applied for three days and T-cell subsets were measured on the days 1, 2 and 3, as well as on day 7 after release from immobilization. Lyt 2-positive cells in the thymus were the most sensitive to stress, showing significant variations. The proportion of immature T-cells increased in the thymus, blood and spleen of the stressed mice. When diazepam or naloxone were administered 30 min before the initiation of stress, these variations tended to decrease. Thus, the ratio of T-cell subsets varied with the duration of immobilization stress. This appeared to be partly mediated by the opioid system and the central nervous system. PMID- 1943463 TI - The direct contractile effect of gastrin releasing peptide on isolated gastric smooth muscle cells of the guinea pig. AB - Smooth muscle cells isolated from the gastric muscle layers of the guinea pig were used to determine whether gastrin releasing peptide (GRP) can cause contraction by exerting a direct action on muscle cells. In addition, the inhibitory effect of 8-( N,N-diethylamino )-octyl-3,4,5-trimethoxybenzoate hydrochloride ( TMB-8 ), an inhibitor of intracellular Ca2+ release, and verapamil, a Ca2+ channel blocker, on the GRP-induced contraction of gastric smooth muscle cells were examined. GRP elicited a contractile response of gastric muscle cells in a dose-dependent manner. The ED50 was 13 pM. TMB-8 significantly inhibited the contractile effect of GRP in gastric muscle cells. These results demonstrate the direct action of GRP on the gastric smooth muscle cells of the guinea pig, and the importance of Ca(2+)-release from intracellular calcium, stores in the contractile response to GRP. PMID- 1943464 TI - Dialyzability and binding of digoxin-like immunoreactive factors (DLIF) with serum macromolecules in uremic patients on hemodialysis. AB - Digoxin-Like Immunoreactive Factors (DLIF) which cross-react with antidigoxin antibodies are present in elevated concentrations in patients on hemodialysis, uremia, hypertensives, liver failure, pre-eclampsia and premature birth. DLIF may have a potential role as a natriuretic hormone with a speculated low molecular weight (less than 1000). We studied the dialyzability and bindings of DLIF with serum components in hemodialysis patients. We analyzed DLIF concentrations in sera and protein free ultrafiltrates of 31 patients and 22 normal volunteers using a fluorescence polarization assay for digoxin. The DLIF concentrations were expressed as nmol/L Digoxin Equivalent. The gel filtration analysis was done using three different Bio-Gel columns with molecular weight cut-offs of 10,000, 20,000 and 40,000. Molecules with lower molecular weight than cut-off were absorbed in the column. Only 3 out of 22 normal volunteers (13.6%) showed measurable DLIF. However 23 out of 31 patients (74.2%) showed measurable DLIF. The concentrations of DLIF were significantly higher in patients with renal failure on hemodialysis (P less than 0.05) by both chi-squared and Fisher's exact test. We observed no statistically significant difference in the concentrations of DLIF in pre and post-dialysis sera, indicating that DLIF were not filtered during hemodialysis. We observed no DLIF activity in the protein free ultrafiltrates of any DLIF positive sera (patients and normal volunteers), indicating that unlike digoxin (where we observed 70-80% of total digoxin concentrations in ultrafiltrates), DLIF were strongly bound to serum components. With Bio-Gel filtration experiments (five different serum pools), we recovered all DLIF activities in the fraction equivalent to the void volume of the column with Bio-Gel P6 and P10 columns, indicating that DLIF were almost completely bound to serum components with molecular weight greater than 20,000. On the other hand, we recovered no DLIF activities in the void volume when the same serum pools were passed through the Bio-Gel P30 column, indicating that DLIF were strongly bound to serum macromolecules with molecular weight less than 40,000. In sharp contrast, when serum containing digoxin was subjected to the same series of experiments, we recovered only 20-30% of digoxin concentrations in void volume with all three columns as expected since digoxin is only 25% bound to albumin (MW 67,000). PMID- 1943465 TI - Chemical sympathectomy with 6-hydroxydopamine potentiates intracerebroventricularly applied bombesin-induced increase in plasma adrenaline. AB - Intracerebroventricular administration of bombesin induced a marked increase in plasma level of adrenaline and a slight increase in that of noradrenaline in rats anesthetized with urethane. The bombesin-induced increase in adrenaline was potentiated by chemical sympathectomy with 6-hydroxydopamine (6-OHDA). On the other hand, adrenalectomy did not affect plasma level of noradrenaline in the bombesin-treated animals. In the splanchnicotomized rats, direct stimulation of the adrenal glands by intravenously administered nicotine increased plasma level of both adrenaline and noradrenaline. These increases were, however, not potentiated by chemical sympathectomy with 6-OHDA. Pretreatment with capsaicin, a potent toxin selective to sensory neurons, potentiated the bombesin-induced increase in plasma level of adrenaline. In these capsaicin pretreated rats, chemical sympathectomy did not potentiate the bombesin-induced increase in plasma level of adrenaline to any great extent. These results suggest that chemical sympathectomy with 6-OHDA potentiated the bombesin-induced increase in plasma adrenaline probably due to a disinhibitory activation of the splanchnic nerve by as yet unidentified but capsaicin sensitive neuron mechanisms. PMID- 1943466 TI - Phosphoramidon inhibits the vasoconstrictor effects evoked by big endothelin-1 but not the elevation of plasma endothelin-1 in vivo. AB - Intravenous injections of big endothelin (ET)-1 (700 pmol/kg) in the pig increased arterial plasma levels of ET-1-like immunoreactivity (ET-1-LI) from 11.1 +/- 0.7 pM to 46.3 +/- 6.7 pM in the control situation and from 11.5 +/- 0.4 pM to 58.2 +/- 17 pM in the presence of the neutral endopeptidase inhibitor phosphoramidon (3 mg/kg). Big ET-1 increased splenic vascular resistance by 29% in the control situation. The vasoconstriction evoked by big ET-1 in the spleen was reduced after phosphoramidon treatment whereas the elevation of arterial ET-1 LI was not influenced. Furthermore the splenic vasoconstriction evoked by ET-1 was reduced after phosphoramidon without influencing plasma ET-1-LI. Also in rats the pressor effect of big ET-1 (1 nmol/kg) was inhibited by phosphoramidon (5 mg/kg) whereas the elevation of plasma ET-1 was not influenced. It is concluded that the vasoconstrictor effects of both big ET-1 and ET-1 are inhibited, but the increase in plasma ET-1 is unaffected by phosphoramidon. PMID- 1943467 TI - Similar high molecular weight forms of growth hormone-releasing hormone are found in rat brain and testis. AB - We have utilized a new radioimmunoassay for rat growth hormone-releasing hormone (GHRH) to investigate the presence of GHRH in different organ systems of adult rat, and specifically the rat central nervous system (CNS). The highest concentration of GHRH was found, as expected, in the hypothalamus, but significant amounts were also located in the brain cortex, predominantly the frontal cortex, as well as in the testis. Smaller amounts were identified in the cerebellum and brain stem. Sephadex and reversed phase high performance liquid chromatography demonstrated that while hypothalamic GHRH exclusively eluted at the position of rat GHRH (1-43), in testis and brain the major form was predominantly (testis) or wholly (brain) of a higher molecular weight. While this molecular species has yet to be further characterized, the data suggest the similar GHRH-like species exist in the CNS as well as the testis. PMID- 1943468 TI - Comparison of efficacy of cysteamine in depleting prolactin immunoreactivity in different hyperprolactinemic animal models. AB - We have examined the effects of cysteamine on its ability to deplete prolactin in various states of hyperprolactinemia. Administration of subtoxic doses of cysteamine (75 and 150 mg/kg,sc) dramatically reduces serum prolactin levels as well as pituitary prolactin content in a dose-dependent manner in estrogen-primed brown Irish ACI female rats. A similar dose-dependent decrease in anterior pituitary prolactin levels was observed in two ectopic prolactin secreting pituitary tumor models (MtTW15 and 7315a). However, a significant reduction in serum prolactin levels was seen in these same tumor bearing animals at only the 150 mg/kg dose of cysteamine. Interestingly, the prolactin content of each of the prolactin secreting tumors, although reduced by cysteamine administration, the effect was neither dose-dependent nor as dramatic as that observed in the anterior pituitary gland proper. These data demonstrate that cysteamine can significantly lower prolactin concentrations in hyperprolactinemia. Further, ectopic prolactin secreting pituitary tissue appears less sensitive to the prolactin-depleting effects of cysteamine. This latter finding may explain, in part, why serum prolactin levels were not as severely reduced in the ectopic tumor bearing female rats as in estrogen-induced hyperprolactinemic animals. PMID- 1943469 TI - Fatty acids markedly lower the threshold for halothane-induced calcium release from the terminal cisternae in human and porcine normal and malignant hyperthermia susceptible skeletal muscle. AB - Malignant hyperthermia is caused by an abnormal increase in Ca2+ levels in skeletal muscle in response to anesthetics, including halothane. Since fatty acid production is elevated in skeletal muscle from individuals with malignant hyperthermia, the effects of fatty acids on the threshold of halothane-induced Ca2+ release were examined. In the absence of fatty acids halothane caused Ca2+ release from porcine and human heavy sarcoplasmic reticulum fractions, but only at concentrations above the clinically relevant range. Oleic acid (20 microM), an unsaturated fatty acid, reduced the threshold at which halothane induced Ca2+ release to concentrations used for anesthesia. Stearic acid, a saturated fatty acid had considerably less effect on the threshold of halothane action. The greater sensitivity of malignant hyperthermia muscle to halothane can be explained by elevated fatty acid production. PMID- 1943470 TI - Effects of monosodium glutamate on lines of chickens having different juvenile exponential growth rates. AB - MSG (4 mg/g BW) or the equivalent molar ratio of NaCl were injected subcutaneously into chicks from four populations of chickens derived from a double selection experiment [(1) low exponential growth rate (EGR) to 14 days of age (14L), (2) high EGR to 14 days of age (14H), (3) low EGR to 42 days of age (42L) and high EGR to 42 days of age (42H)]. MSG significantly influenced growth in chickens, but the absolute effect was genotype and sex dependent. Weights of abdominal fat pads were ranked among lines according to the sequence 42H, 14H, 42L and 14L. MSG significantly increased fat pad size by 51%, independent of genotype or sex. MSG significantly decreased breast weight in females and males by 7%. The higher percent fat pads and lower breast weights associated with MSG are indicative of growth due to fat accretion rather than protein deposition. PMID- 1943471 TI - Flumazenil and bupivacaine-induced toxicity: inverse agonist type activity. AB - The purpose of this study was to investigate the influence of flumazenil on bupivacaine-induced acute toxicity, 10 groups of mice were previously treated by a 1, 0.5, 0.25 and 0.125 mg/kg single dose of flumazenil or saline 15 minutes before an injection of bupivacaine (50 mg/kg: exp. 1 and 60 mg/kg: exp.2). The convulsant activity, the period of latency to convulse and the induced mortality were assessed in each group. The bupivacaine-induced mortality was increased by flumazenil. Also, the convulsant activity was increased by flumazenil and the period of latency to convulse was proportionally decreased with increasing doses of flumazenil for the two tested doses of bupivacaine. PMID- 1943472 TI - The membrane-stabilizing action of zinc carnosine (Z-103) in stress-induced gastric ulceration in rats. AB - Zinc compounds have been shown to antagonize various types of gastric ulceration in rats. Zinc carnosine (Z-103), a newly developed agent was, therefore, examined for its antiulcer effect in stress-induced ulceration and also its membrane stabilizing action in rat stomachs. Cold-restraint (restrained at 4 degrees C for 2 h) stress induced severe hemorrhagic lesions together with increased mast cell degranulation and beta-glucuronidase release in the gastric glandular mucosa. Z 103 pretreatment with a single oral dose (3, 10 or 30 mg/kg) reversed these actions in a dose-dependent manner. When the compound was incubated in concentrations of 10(-7, 10(-6), 10(-5) or 10(-4) M, with isolated hepatic lysosomes, it significantly reduced the spontaneous release of beta-glucuronidase in the medium. The present study not only demonstrates the antiulcer effect of Z 103 but also indicates that the protective action is likely to be mediated by its membrane-stabilizing action on mast cells and lysosomes in the gastric glandular mucosa. PMID- 1943473 TI - Highly insulin-responsive isolated rat heart muscle cells yielded by a modified isolation method. AB - Freshly isolated adipocytes or cardiac myocytes appear to be subject to unspecific stimulation during isolation and subsequent handling, e.g. with respect to glucose transport. We have developed a modified procedure that yields rat cardiomyocytes with a very low basal, i.e. non stimulated hexose uptake rate (ca. 3 pmol * s-1 * mg protein-1 at 1 mM sugar), as compared to data reported by others. This low value correlates with the reported oxygen consumption of non beating, isolated rat hearts, when these are perfused with glucose as the only substrate. The basal rate of glucose uptake in our quiescent cardiomyocytes is slightly lower than the value measured by others in beating rat hearts in vivo. Insulin (10 nM) stimulates 2-deoxy-D-glucose uptake 8- to 20-fold and 3-O-methyl D-glucose uptake 14- to 20-fold, as compared to control. This insulin effect is markedly larger than that usually observed in isolated cardiomyocytes, but it is similar in magnitude to the stimulation of glucose transport reported for isolated, perfused rat hearts. In these cells, new stimulatory effects on the glucose transport, e.g. that of sulfhydryl reagents like phenylarsine oxide, become apparent. We conclude that the cardiomyocytes obtained by this modified method exhibit a basal glucose transport rate that is close to physiological values. These cells represent a new highly responsive model to detect and to investigate the effects of glucose transport stimulators (insulin, contraction etc.). PMID- 1943474 TI - Enhanced haloperidol-induced prolactin stimulation with chronic neuroleptic treatment in the rat. AB - Animals were treated either acutely, or chronically for 21 days, with a low dose (0.1 mg/kg) of haloperidol, then sacrificed to obtain trunk blood for radioimmunoassay of prolactin (PRL) level. PRL concentrations on day 21 of chronic treatment were greater than two-fold those produced by acute neuroleptic. Challenge with apomorphine to rats withdrawn for 48 hours revealed similar PRL reductions as a group withdrawn from chronic vehicle injections. PMID- 1943475 TI - Tumor necrosis factor induces activation of mitochondrial succinate dehydrogenase. AB - We have studied TNF-induced changes in mitochondrial enzymes. One enzyme, succinate dehydrogenase (SDH), is specifically activated in TNF sensitive cells including U937 (human monocytic), WEHI-164 (murine fibrosarcoma), and ME-180 (human cervical carcinoma). SDH is activated by TNF concentrations which also cause cytolysis, however the enzyme activity is elevated several hours before maximum cytotoxicity is observed. In contrast, TNF does not activate SDH in TNF resistant variants derived from U937 and WEHI-164. PMID- 1943476 TI - Kinetic analysis of the preserved rat liver by isolated perfusion with ammonium chloride as a load. AB - Oxygen consumption and urea synthesis from ammonium chloride (NH4Cl) were investigated in the liver preserved in University of Wisconsin solution at 4 degrees C for 24 hours using an isolated rat liver perfusion system in which the perfusate contained five different concentrations of NH4Cl. When a Michaelis Menten equation was applied to oxygen consumption and urea synthesis against NH4Cl concentration, the preserved liver showed smaller increase in oxygen consumption rate and larger Km of urea synthesis for NH4Cl than the fresh liver. The ratio of respiration velocity without any substrate to maximal velocity (v/Vmax), which reflects the mitochondrial functional reserve, was 55.9 +/- 4.1% and 41.5 +/- 4.8% in the preserved and fresh liver, respectively (p less than 0.05). From the viewpoint of work-cost relationship, it was shown that the mitochondrial function in the preserved liver was deteriorated. On the other hand, conventional mitochondrial study after rewarming and reoxygenation but before NH4Cl load revealed no deterioration of mitochondrial function after preservation. These results indicate that it is necessary to take the metabolic load on the reperfused liver into account when assessing graft viability, and that high v/Vmax suggests decrease in the reserve of mitochondrial function under consideration of the metabolic load. PMID- 1943477 TI - Platelet activating factor induces expression of early response genes c-fos and TIS-1 in human epidermoid carcinoma A-431 cells. AB - The effect of platelet activating factor (PAF) on the induction of early response genes was investigated in A-431 cells (human epidermal carcinoma cells). PAF induced a transient expression of c-fos and TIS-1 mRNA in a time- and dose dependent manner. As low as 10(-10) M PAF caused detectable expression of these genes with a maximum observed at 10(-7) M. In the presence of cycloheximide, increases in the gene expression were noticeable at 20 min and peaked between 30 60 min. A lack of induction with lyso-PAF, an inactive PAF metabolite, confirmed the specificity of PAF towards this expression. The cells pretreated with CV 6209, a PAF receptor antagonist, did not show any induction of these genes by PAF. It is concluded that PAF causes induction of the early response genes c-fos and TIS-1 in a structurally specific and receptor dependent manner. This finding offers a new role for PAF at the nuclear level and may have important implications in the long term effects of PAF in pathophysiological conditions. PMID- 1943478 TI - Intercellular communication through gap junctions: a potential role in pharmacomechanical coupling and syncytial tissue contraction in vascular smooth muscle isolated from the human corpus cavernosum. AB - Kinetic and steady-state protocols were used to examine the effects of disruption of intercellular communication with heptanol, on contractile responses elicited by activation of the alpha 1-adrenergic receptor in human corporal vascular smooth muscle. For the steady-state studies, strips of corporal tissue from 19 patients were submaximally precontracted with phenylephrine (PE) and then relaxed by the cumulative addition of heptanol. Heptanol completely and reversibly relaxed all tissues studied in a concentration-dependent manner. The heptanol concentration response data were then computer fit to the general logistic equation to obtain pEC50 (negative logarithm of the concentration that elicits one-half of the maximal effect) and slope factor values, with Emax (maximal relaxation) set to 100%. The mean pEC50 and slope factor values, respectively, were 2.86 +/- 0.04 and 1.86 +/- 0.17. Furthermore, kinetic studies on corporal tissues from a subset of the patient population (11 patients) revealed that preincubation of tissues with 2 mM heptanol caused a significant decrease in both the rate and magnitude of PE-induced contractions in all tissues studied, without affecting the rate constant for onset of contraction (k(obs)). The present results on intact tissue extend our previous observations on cultured corporal cells, and support the supposition that intercellular communication through gap junctions may play an important role in the initiation, maintenance and modulation of alpha 1-adrenergic contractions in human vascular smooth muscle. PMID- 1943479 TI - Cocaine conditioned place preference is attenuated by chronic buprenorphine treatment. AB - Previous research shows that buprenorphine (BUP), a mixed opioid agonist antagonist, reduces cocaine use in humans and suppresses cocaine self administration in monkeys. The present study found that BUP reduces cocaine's ability to condition a place preference in rats. Compared to vehicle treated rats, rats treated with BUP 2 times/day for 2 weeks spent significantly less time in the cocaine conditioned place compared to their respective saline trained controls. No conditioned place preference was shown for BUP alone. These results further implicate a role for the opioid system in cocaine use and stress the importance of differentiating chronic vs. acute opioid effects. PMID- 1943480 TI - Functional evidence for the presence of a phosphoramidon-sensitive enzyme in rat brain that converts big endothelin-1 to endothelin-1. AB - Endothelin-1 (ET-1) is produced from its precursor, big endothelin-1 (BigET-1), by a putative endothelin-converting enzyme (ECE), but it is not known whether the enzyme is present in the brain. This study was conducted to examine the central hemodynamic effects of BigET-1 and to indirectly determine the presence of an ECE in rat brain. Cardiovascular effects of centrally administered BigET-1 and ET-1 were examined in anesthetized, ventilated rats. BigET-1 (100 pmol) or ET-1 (10 pmol) applied to the IV ventricle produced similar prolonged decreases in mean arterial pressure (MAP) and renal blood flow (RBF). Thus, peak decreases with BigET-1 were (mean +/- S.E.): MAP = -35 +/- 4%; RBF = -27 +/- 5%, while those with ET-1 were: MAP = -36 +/- 5%; RBF = -29 +/- 9%. Pretreatment with phosphoramidon, a metalloprotease inhibitor (90 nmol), abolished the hemodynamic responses elicited by BigET-1 (MAP = -9 +/- 2%; RBF = -3 +/- 2%) but not those produced by ET-1. These data indicate that; i) conversion of BigET-1 to ET-1 in the brain is essential for the expression of hemodynamic actions and ii) a metalloprotease capable of converting BigET-1 to ET-1 is present in rat brain. PMID- 1943481 TI - Nephrotoxicity of halogenated alkenyl cysteine-S-conjugates. AB - In 1916 a relationship was postulated between the occurrence of aplastic anaemia in cattle and the soy bean meal that they had been fed, which had been extracted with trichloroethylene. The toxic compound was later identified as S-(1,2 dichlorovinyl)-L-cysteine (DCV-Cys). In addition to effects on the hemopoietic system it also produced nephrotoxicity in calves. In rats only renal tubular necrosis was found. Further research demonstrated that other halogenated hydrocarbons produced similar nephrotoxicity. The haloalkenyl cysteine-S conjugates (Cys-S-conjugates) have extensively been studied; this has provided new insight into the biochemical processes that lead to nephrotoxicity. It has been shown that a combination of transport processes and specific metabolic pathways, resulting in reactive intermediates that bind to cellular macromolecules, makes the kidney vulnerable to the noxious effects of the haloalkenyl Cys-S-conjugates. The first part of this review gives a brief overview of the bioactivation of the haloalkenes; in the second part the present knowledge of the underlying mechanisms of cytotoxicity will be outlined. PMID- 1943482 TI - Inhibition of acetaminophen activation by ethanol and acetaldehyde in liver microsomes. AB - Mechanisms of the inhibitory effect of ethanol on acetaminophen hepatotoxicity are controversial. We studied the effects of ethanol and acetaldehyde, an oxidative metabolite of ethanol, on NADPH-dependent acetaminophen-glutathione conjugate production in liver microsomes. Ethanol at concentrations as low as 2mM prevented the conjugate production noncompetitively. Acetaldehyde also inhibited acetaminophen-glutathione conjugate production at concentrations as low as 0.1mM that is comparable with those observed in vivo after social drinking. Acetaldehyde may be involved in ethanol-induced inhibition of acetaminophen hepatotoxicity. PMID- 1943483 TI - Stability of antisense DNA oligodeoxynucleotide analogs in cellular extracts and sera. AB - Antisense DNA oligodeoxynucleotides can selectively inhibit the expression of individual (undesirable) genes and thus, have potential in the treatment of cancer and viral diseases. A prerequisite to their use as therapeutic agents is information on the stability of oligodeoxynucleotides, and their structurally modified analogs, in the biological milieu. To this end, degradation of 5' end and internally [32P] labelled unmodified DNA oligodeoxynucleotide (D-oligo) and analogs containing phosphorothioate (S-oligo), methylphosphonate (MP-oligo), and novel alternating methylphosphonate and phosphodiester (Alt-MP-oligo) internucleoside linkages was studied in Hela cell nuclear extract, S100 cytoplasmic extract, normal human serum and calf serum at 37 degrees C. Both 5' end and internally labelled D-oligos showed complete degradation within 30 min incubation in human serum at 37 degrees C. In any given medium, the D-oligo was the least stable oligodeoxynucleotide to nuclease degradation whereas the Alt-MP, MP and S-oligos were generally of comparable stability and all relatively more stable than D-oligo. Interestingly, MP and Alt-MP-oligos also exhibited greater resistance to phosphatases in cellular extracts compared to D and S-oligos. Under the conditions of the experiments, increasing degradation for any given oligonucleotide was observed in the order: S100 cytoplasmic extract less than nuclear extract less than normal human serum less than calf serum. In a study involving alpha-MEM cell culture medium containing 10% heat inactivated fetal calf serum (heated to 56 degrees C for 1 hour), the D-oligo was found to be rapidly degraded (degradation evident within 10 mins) whereas degradation products for the S-oligo were observed within 1 hour. In contrast, the Alt-MP oligo remained stable throughout the 3 hour experiment. These results indicated that in cell culture medium containing heat inactivated serum Alt-MP oligo was more stable than D- and S-oligos. PMID- 1943484 TI - Use of naloxone in the assessment of opiate dependence. AB - All subjects participating in an outpatient study comparing treatments for opiate dependence were given a naloxone challenge to document their level of dependence. Subjects were assessed at 0, 10, 20, and 30 minutes following the administration of intramuscular naloxone (0.4 mg) using an opiate withdrawal assessment scale and measurements of pupillary diameter. Subjects' self reports of daily dollar amounts of opiate use and time since last use were also examined for possible correlation with withdrawal scale scores and pupillary measurements. A significant negative correlation was obtained between pupil diameter and time since last reported use of an opiate. Results indicated that the scale was a reliable indicator of opiate dependence. Ways in which it might be improved are discussed. PMID- 1943485 TI - TRH reverses the ECG and EEG ischemic changes induced by massive hemorrhage in rats. AB - In a rat model of volume-controlled hemorrhagic shock causing the death of all saline-treated animals within 30 min of treatment, the intravenous bolus injection of thyrotropin- releasing hormone tartrate (TRH-T) at the dose of 4 mg/kg induced the prompt and sustained disappearance of the ECG and EEG signs of heart and brain ischemia, along with the reversal of hypotension and respiratory depression and with 100% survival rate at the end of the 2 h observation period. These data confirm that, in a pre-terminal condition induced by massive hemorrhage, timely treatment with TRH-T will restore heart and brain perfusion to levels compatible with survival and with functional recovery from ischemia and maintain it at those levels for some hours. PMID- 1943486 TI - Chronopharmacological study of furosemide; (VIII) influence of feeding restriction. AB - We have previously reported that a time-dependent variation is observed in the diuretic effect of furosemide and the light-dark cycle is a potent zeitgeber for this chronopharmacological phenomenon of the agent in rats. The present study was undertaken to examine whether a time of food intake is another zeitgeber for this event. In study I, rats were maintained with free access to food for 3 weeks. Furosemide (30 mg/kg) was given orally at 12 am or 12 pm. Urine was collected for 8 hours after the agent and urinary excretion of sodium and furosemide were determined. Thereafter, these rats were maintained under a daytime-restricted feeding schedule (9 am-11 am) for 3 weeks (study II) and a night-time-restricted feeding schedule (9 pm-11 pm) for 3 weeks (study III). The identical protocol of study I was repeated at the end of study II and III. Diuretic effect of furosemide and its urinary excretion were significantly greater at 12 am than at 12 pm in study I and III. However such an administration time-dependent change in the effect of furosemide and its urinary amount disappeared in study II. These data indicate that a time of food intake is another potent zeitgeber for the time dependent variation in the diuretic effect of furosemide. PMID- 1943487 TI - Drug distribution studies with microdialysis: I. Tissue dependent difference in recovery between caffeine and theophylline. AB - Microdialysis was applied to estimate concentrations of caffeine and theophylline in vitro or in vivo in blood, adipose tissue, muscle, liver and brain of rats. The in vivo and in vitro recovery of a compound was estimated by perfusing the dialysis probe with varying concentrations of caffeine and theophylline. The difference between the concentration in the dialysate and the concentration in the perfusion medium was plotted against the concentration in the perfusion medium and the slope of the resulting line was taken as an estimate of the recovery (difference method). In all experiments caffeine (20 mg/kg sc) and theophylline (20 mg/kg sc) were administered simultaneously. The recovery in vitro was virtually identical for caffeine and theophylline. The in vivo recovery of theophylline was significantly smaller than the recovery of caffeine in brain, liver, muscle and adipose tissue. The difference in recovery was significantly larger in the brain than in other tissues. The results show that the transport of a substance from the tissue to the dialysis probe may differ between tissues and between chemically very similar compounds. It is shown that the recovery of theophylline rapidly declines after death ensues which shows that energy dependent processes are involved in the transport to the dialysis probe and not solely passive diffusion. It is suggested the differences in transport over brain capillaries explain the difference between caffeine and theophylline. It is concluded that the use of internal standards in microdialysis experiments requires validation in every specific application. PMID- 1943488 TI - Drug distribution studies with microdialysis. II. Caffeine and theophylline in blood, brain and other tissues in rats. AB - Microdialysis was applied to estimate the pharmacologically active concentration of caffeine and theophylline in blood, adipose tissue, muscle, liver and brain of rats. The concentration of the drugs in the extracellular space was estimated by perfusion with varying concentrations of the drug through the microdialysis probe (difference method). Caffeine (20 mg/kg) was found to be evenly distributed with a free concentration of approximately 120 microM. Theophylline concentration in the brain was 91 microM and in other tissues approximately 120 microM. The rate of penetration into brain extracellular space was higher for caffeine than for theophylline. It is suggested that the lower levels of theophylline attained in the brain may to some extent explain the differences in clinical action profile between caffeine and theophylline. PMID- 1943489 TI - Drug distribution studies with microdialysis. III: Extracellular concentration of caffeine in adipose tissue in man. AB - Microdialysis was applied to estimate the extracellular concentration of caffeine in subcutaneous abdominal adipose tissue of five healthy volunteers after oral administration of approximately 5 mg/kg (300 or 400 mg) of caffeine. The peak extracellular levels were in the range of 20 - 80 microM. The time-course in blood and in extracellular fluid was similar but the plateau concentrations were not closely correlated. The estimated mean concentration of five individuals was similar in blood and extracellular fluid. The intraindividual variation between probes was found to be small compared to the interindividual variation (8% versus 43%). It is concluded that microdialysis yield useful data on drug distribution in man and that distribution to adipose tissue may not strictly follow the concentrations in blood. A comparison with available information of the in vitro properties of caffeine shows that the levels attained in the extracellular fluid were too small to significantly affect phosphodiesterase but sufficiently high to block adenosine receptors. PMID- 1943490 TI - Incorporation of lipids labeled with various fatty acids into the cytoskeleton of aggregating platelets. AB - Earlier studies showed that during the first 20 to 25 seconds of aggregation induced by thrombin (0.1 U/mL) or adenosine diphosphate (ADP) (2 microM) of rabbit or human platelets prelabeled with [3H]palmitic acid, labeled lipid became associated with the cytoskeleton (isolated after lysis with 1% Triton X-100, 5 mM EGTA [ethylene glycolbis-(beta-aminoethyl ether(N,N,N',N'-tetraacetic acid] in the presence of 0.5 mM leupeptin and 50 mM benzamidine). In comparison with labeled lipid in intact platelets, the labeled lipid that was associated with the cytoskeleton was enriched in phospholipids and ceramide. To determine whether these effects were specific for lipids labeled with palmitic acid, we studied rabbit platelets in which lipids had been labeled by incubation of the platelets with pairs of 14C- or 3H-labeled palmitic, stearic, arachidonic, and linoleic acids. Examination of the distribution of label among the lipid classes of intact platelets showed that phospholipids contained most of the label. Under the conditions of limited, thrombin-induced aggregation used, labeled lipids were not lost from the platelets and the distribution of label among the lipid classes was essentially unchanged. There were major differences in the incorporation of labeled lipids into the cytoskeleton. The greatest incorporation (2.1 to 2.8% of the label in the platelets) was observed with palmitic acid-labeled lipids; by direct comparison, only 44% as much of the label of stearic acid-labeled lipids, 21% as much of the label of linoleic acid-labeled lipids, and only 6% as much of the label of arachidonic acid-labeled lipids was incorporated into the cytoskeleton.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943491 TI - Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition on human gut mucosa. AB - Mevalonic acid is an important biochemical intermediate in cholesterol synthesis and other processes involved in cell replication. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is the enzyme which catalyzes mevalonic acid synthesis. To determine whether a potent competitive inhibitor of this enzyme, the drug simvastatin, may have an adverse effect on enterocyte cell replication and cholesterol metabolism, small intestinal biopsies from nine hypercholesterolemic subjects were obtained before and during treatment with simvastatin as a lipid-lowering agent. Histologic review of biopsies in a blinded manner detected no change in ratio of villous length to crypt length or in mitotic index which might indicate altered cell replication. Similarly, no significant change in measured activity of HMG-CoA reductase activity was observed. In spite of the high exposure of jejunal mucosal cells to this potent competitive inhibitor of a key enzyme, no adverse effect on growth could be detected. PMID- 1943492 TI - Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue. AB - Acylation stimulating protein (ASP) is a 14 kDa plasma protein which causes in vitro triacylglycerol synthesis in human adipocytes and fibroblasts to increase substantially. ASP was found to stimulate human adipose tissue microsomal glycerophosphate acyltransferase and diacylglycerol acyltransferase activities by 23% and 90%, respectively. However, phosphatidate phosphohydrolase activity showed no increase in activity, nor did microsomal acyl-CoA synthetase activity. Moreover, ASP did not decrease the apparent Km of diacylglycerol acyltransferase (DGAT), but rather increased its apparent Vmax suggesting direct interaction of ASP with DGAT. PMID- 1943493 TI - Effect of fish oil supplementation on the excretion of the major metabolite of prostaglandin E in healthy male subjects. AB - We investigated the effect of fish oil supplementation on the synthesis of prostaglandin E (PGE) in vivo by measuring the excretion of its catabolite, PGE M, in 24-hr urine by gas chromatography/mass spectrometry. Forty healthy male volunteers (24-57 years of age) consumed a controlled basal diet providing 40% of energy from fat (P/S ratio about 0.8:1), 130 mg/1000 kcal cholesterol, and a minimum of 22 mg/day of alpha-tocopherol (alpha-T), for three experimental periods lasting a total of 28 weeks. During period 1 (10 weeks) the diet was supplemented with placebo (PO) capsules (15 X 1 g/day) consisting of a blend of fats approaching the fatty acid profile of the basal diet. This was followed by a second 10-week period during which the subjects received 15 X 1 g/day capsules of fish oil concentrate (FOC). During period 3 (8 weeks) they continued the 15 g/day intake of FOC but received an additional 200 mg/day of alpha-T. PO and FOC capsules contained 1 mg alpha-T/g fat as antioxidant. A 14% reduction of PGE-M excretion was observed after 10 weeks of FOC supplementation (period 2), compared to an identical period of placebo supplementation (period 1), P = 0.009. PGE-M excretion during the last week of period 3 was not significantly different from that at the end of period 2. The reduction in PGE synthesis in response to the relatively high marine oil supplementation was large in many subjects participating in this study. PMID- 1943494 TI - Sesamin is a potent and specific inhibitor of delta 5 desaturase in polyunsaturated fatty acid biosynthesis. AB - Incubation with sesame oil increases the mycelial dihomo-gamma-linolenic acid content of an arachidonic acid-producing fungus, Mortierella alpina, but decreases its arachidonic acid content [Shimizu, S., K. Akimoto, H. Kawashima, Y. Shinmen and H. Yamada (1989) J. Am. Oil Chem. Soc. 66, 237-241]. The factor causing these effects was isolated and identified to be (+)-sesamin. The results obtained in experiments with both a cell-free extract of the fungus and with rat liver microsomes demonstrated that (+)-sesamin specifically inhibits delta 5 desaturase at low concentrations, but does not inhibit delta 6, delta 9 and delta 12 desaturases. Kinetic analysis showed that (+)-sesamin is a noncompetitive inhibitor (Ki for rat liver delta 5 desaturase, 155 microM). (+)-Sesamolin, (+) sesaminol and (+)-episesamin also inhibited only delta 5 desaturases of the fungus and liver. These results demonstrate that (+)-sesamin and related lignan compounds present in sesame seeds or its oil are specific inhibitors of delta 5 desaturase in polyunsaturated fatty acid biosynthesis in both microorganisms and animals. PMID- 1943495 TI - Acylation of lyso platelet-activating factor by splenocytes of the rainbow trout, Oncorhyncus mykiss. AB - In mammalian systems, platelet-activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3 phosphocholine, (PAF) is rapidly inactivated by a deacetylation/reacylation system that produces 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine which is highly enriched in arachidonic acid. There is some evidence that n-3 fatty acids may have an impact on this system in humans but the nature of this impact is unclear. In rainbow trout, n-3 fatty acids are known to be essential dietary components which are derived through the food chain. Substantial quantities of n-3 fatty acids are found in trout membrane phospholipids. We show here that in sharp contrast to mammalian cells, trout cells acylate lyso platelet-activating factor, alkyl-GPC, 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine, (lyso-PAF) with a high degree of specificity for n-3 fatty acids. When [3H]lysoPAF was incubated with these cells, only three molecular species of alkylacylglycerophosphocholine were produced, and 92% contained n-3 fatty acids. Since isolated membranes yielded similar results, it appears that the acylation proceeds via a coenzyme A independent transacylase as found in mammalian systems. PMID- 1943496 TI - Differential effects of ursodeoxycholic acid and ursocholic acid on the formation of biliary cholesterol crystals in mice. AB - The preventive effect of 3 alpha, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid (ursocholic acid) and ursodeoxycholic acid on the formation of biliary cholesterol crystals was studied in mice. Cholesterol crystals developed with 80% incidence after feeding for five weeks a lithogenic diet containing 0.5% cholesterol and 0.25% sodium cholate. When 0.25% ursocholic acid or ursodeoxycholic acid was added to the lithogenic diet, the incidence as well as the grade (severity) of the gallstones were reduced. Plasma and liver cholesterol levels were decreased by ursodeoxycholic acid but not by ursocholic acid. Gallbladder cholesterol and phospholipid levels were decreased by both bile acids. The biliary bile acid level was decreased by ursocholic acid but not by ursodeoxycholic acid. After feeding ursocholic acid, its level in the bile was about 25% and the levels of cholic acid and beta-muricholic acid decreased. Fecal sterol excretion was not changed by ursocholic acid, but was increased by ursodeoxycholic acid. After feeding ursocholic acid, fecal excretion of deoxycholic acid, cholic acid, and ursocholic acid increased. No differences were found between mice, with or without gallstones, in plasma and liver cholesterol levels, biliary phospholipid and bile acid levels, fecal sterol and bile acid levels, and biliary and fecal bile acid composition. The results suggest that the lower incidence of crystal formation after treatment with ursocholic acid is probably by a different mechanism than with ursodeoxycholic acid. In the mouse model, ursodeoxycholic acid exerts its effect at least partially, by decreasing cholesterol absorption. Ursocholic acid is well absorbed and excreted into bile and transformed into deoxycholic acid by the intestinal microflora in mice. PMID- 1943497 TI - Phospholipid requirement of progesterone 5 alpha-reductase from gastric mucosa microsomes of guinea pig. AB - Progesterone 5 alpha-reductase partially purified from gastric mucosa microsomes was stimulated by short-chain synthetic phosphatidylcholines (PC), such as dilauroyl PC, but not by various PC from biological sources. Phosphatidylserine (PS) activated the gastric 5 alpha-reductase to a limited extent compared to the liver 5 alpha-reductase described previously [Ichihara, K., and Tanaka, C. (1987) Biochem. Biophys. Res. Commun. 149, 482-487]. In search of more effective phospholipid activators, we tested the effects of various lysophospholipids on 5 alpha-reductase activity. Strongly stimulatory effects were observed when lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) were used instead of PC and phosphatidylethanolamine. Examination of synthetic lysoPC and lysoPE differing in acyl chain lengths showed that fatty chains of 12 to 16 carbons were effective in stimulating the 5 alpha-reductase. By contrast, other lysophospholipids such as lysophosphatidic acid, lysophosphatidylglycerol or lysophosphatidylserine (lysoPS) greatly inhibited 5 alpha-reductase activity. These findings suggest that gastric 5 alpha-reductase may be under dual regulation; lysoPC and lysoPE may play important roles as positive effectors, whereas lysophosphatidic acid, lysophosphatidylglycerol and lysoPS act as negative effectors in progesterone 5 alpha-reductase regulation. PMID- 1943498 TI - Evidence of extensive phospholipid fatty acid methylation during the assumed selective methylation of plasma free fatty acids by diazomethane. AB - We compared a conventional method (Method I) for measuring plasma free fatty acid (FFA) concentrations with two more rapid procedures (Method II and Method III). Method I required total lipid extraction, separation of FFA by thin-layer chromatography, methylation, and gas-liquid chromatographic analysis of the fatty acid (FA) methyl esters. Method II was a colorimetric procedure. Method III relied upon diazomethane's presumed ability to selectively methylate FFA even in the presence of FA esters. The three methods were compared using plasma from fasted and from fed nude mice, tumor-bearing mice (MX-1 and ZR-75-1 human mammary carcinomas), and controls. Method II, was less reliable than Method I, but both gave similar mean values for plasma FFA levels in fasted mice. Both Methods I and II also showed similar lowering of plasma FFA levels after feeding previously fasted mice. Method III consistently gave values that were far greater than those obtained using Methods I and II. Moreover, highly significant differences between fasted and fed mice were obscured by direct methylation of plasma FFA with diazomethane (Method III). The excess FA methyl esters formed in Method III were derived from plasma phospholipids, but not from plasma triacylglycerols. After feeding fasted mice, plasma free palmitic acid and oleic acid levels fell (Method I); by contrast, the excess "FFA" formed by methylation of plasma phospholipid FA increased two-fold and fourteen-fold, respectively. Caution is therefore advised in the use of direct methylating agents when measuring total and individual plasma FFA levels. PMID- 1943499 TI - Maternal protein deficiency in rat: effects on central nervous system gangliosides and their catabolizing enzymes in the offspring. AB - Maternal protein deficiency imposed on rats a month prior to conception, and during gestation and lactation, resulted in a significant cell loss in cerebrum, cerebellum, brain stem and spinal cord of pups at weaning. The cerebellum was the most affected central nervous system (CNS) region; it contained only 25% of the normal cell number. Undernourished pups were also found to have a lower concentration of total gangliosides in cerebrum as compared to that of controls. However, the total ganglioside concentration was unaffected in the cerebellum, brain stem and spinal cord by maternal undernutrition. In all regions, undernutrition caused significant changes in the proportions of individual gangliosides; these alterations were region-specific. Sialidase, beta galactosidase, beta-glucosidase, and beta-hexosaminidase, which are involved in the catabolism of gangliosides, showed higher activities in all the regions of undernourished pups, suggesting that these enzymes may play a role in maintaining the porportions of various ganglioside fractions. PMID- 1943500 TI - Supplementation with evening primrose oil in atopic dermatitis: effect on fatty acids in neutrophils and epidermis. AB - We investigated the effect of oral supplementation with evening primrose oil, containing 72% linoleic acid (18:2n-6) and 10% gamma-linolenic acid (18:3n-6), on the epidermal and neutrophil phospholipid fatty acid composition in 15 patients with atopic dermatitis (AD). Three different dose levels, 4, 8 and 12 capsules per day containing 0.5 g oil, were given to three groups of patients. The only n 6 fatty acid showing a significant (p less than 0.05) dose-related increase was dihomo-gamma-linolenic acid (20:3n-6) in neutrophil phospholipids. The highest dose increased dihomo-gamma-linolenic acid by 45% in neutrophil phospholipids, by 46% in lesion-free epidermal phosphatidylcholine, and by 15% in lesion-free epidermal phosphatidylethanolamine. In both lesional and lesion-free epidermis, supplementation resulted in a rise in the ratio between n-6 and monounsaturated fatty acids, reaching significance (p less than 0.05) in lesional epidermis. This study shows that moderate and favorable fatty acid changes can be obtained in the epidermis of AD patients, when given 6 g per day of oil rich in n-6 fatty acids. The abnormal lipid and fatty acid pattern of the atopic epidermis may be involved in the pathogenesis of the disease, and should therefore be the target for future therapeutic approaches with fatty acid supplements. PMID- 1943501 TI - Liver changes in patients with hyperthyroidism. AB - We studied liver changes in the hepatic biopsies of five patients with hyperthyroidism. A characteristic histopathologic picture consisting of mild to moderate intrahepatocytic cholestasis, lobular inflammatory infiltrate with some eosinophils, and Kupffer cell hyperplasia was found in all cases. We discuss the specificity, clinicopathological correlations and the possible pathophysiology of these lesions. PMID- 1943502 TI - Caliber of splenic and hepatic arteries and spleen size in cirrhosis of different etiology. AB - The caliber of the splenic and hepatic arteries, the hepatic to splenic artery ratio and the spleen size (area of widest spleen section) were evaluated by real time ultrasonography (US) in 88 patients affected by liver cirrhosis of different etiology (26 alcoholic cirrhosis, 43 hepatitis B virus (HBV) related cirrhosis, 8 cryptogenic cirrhosis and 11 primary biliary cirrhosis) and in a control group of 21 normal subjects, in order to assess the possible influence of the etiology of the disease on these morphological parameters. The mean caliber of the hepatic artery was larger, and the mean caliber of the splenic artery smaller in alcoholic than in HBV-related, cryptogenic and in primary biliary cirrhosis. This difference is emphasized when considering the hepatic to splenic artery ratio: this parameter was never greater than 0.9 in all cases of primary biliary cirrhosis, in 38 out of 43 patients with HBV-related cirrhosis and in 6 out of 8 cryptogenic cirrhosis, while in the alcoholic group only in one out of 26 was it less than 0.9. The sensitivity, specificity and accuracy of this ratio in differentiating alcoholic from non-alcoholic cirrhosis was 96%, 88% and 91%, respectively. Splenomegaly resulted more in primary biliary cirrhosis, in HBV related cirrhosis and in cryptogenic cirrhosis than in the alcoholic form. Finally, a significant correlation was found in all groups of cirrhotic patients between the diameter of the splenic artery and the spleen size. These results show that some ultrasonographic morphological features of liver cirrhosis differ according to its varied etiology, probably reflecting different pathophysiological mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943503 TI - Portal pressure in patients with exudative ascites in the course of acute hepatitis B. AB - We describe three patients who developed ascites during the course of acute viral hepatitis B. Two of them had exudative ascites, with a high protein and cell content, and the other transudative ascites, with low protein and cell content. Both patients with exudative ascites had a benign clinical course, and their liver disease was milder than in the patient with transudative ascites, who had signs of severe liver failure and a submassive hepatic necrosis on liver biopsy. Moreover, the patient with transudative ascites had evidence of portal hypertension (as indicated by a hepatic vein pressure gradient of 12.5 mmHg, normal 1-6 mmHg), whereas patients with exudative ascites did not (hepatic vein pressure gradient of 5 and 5.5 mmHg, respectively). These data support our previous suggestion that "exudative" ascites during acute viral hepatitis B represents a self-limited immunopathetic sign that is not related to portal hypertension or severe hepatic disease. PMID- 1943504 TI - Clinicopathological analysis of alcoholic liver disease complicating chronic type C hepatitis. AB - Seventy-six chronic alcoholics in Japan were evaluated for histological changes of liver needle biopsies, Chiron C100 antibody (C-100) for hepatitis C virus, as well as clinical and laboratory data. In biopsies, the presence of necroinflammations within the parenchyma, lymphocytic reaction in the portal tracts, or both, might indicate non-A, non-B (NANB) chronic hepatitis. Using these histological criteria, the patients were previously classified into two groups: alcoholic liver disease (ALD) alone and ALD complicating NANB chronic hepatitis. The C100-positive ratio was found to be 12% in the former group and 69% in the latter. Further clinical and laboratory comparison revealed that there were significant differences in gamma-glutamyl transpeptidase, gamma-globulin, and adenosine deaminase levels in the sera between the ALD alone and the ALD complicating NANB chronic hepatitis groups. Since some chronic alcoholics are also affected by chronic type C hepatitis, detailed evaluations of the liver biopsy and C-100 assay are required for the differentiation of these hepatic disorders. PMID- 1943505 TI - Transplantation studies on human and duck hepatocytes in athymic nude mice. AB - For determination of the most suitable tissue for heterotopic transplantation of exogenous hepatocytes, dissociated hepatocytes or small pieces of liver tissue were transplanted into the spleen, adipose tissue and inside the capsule of the kidney of BALB/c mice. Survival of syngeneic grafts of dissociated hepatocytes was highest in the spleen and that of pieces of liver tissue in the adipose tissue, but only the latter system was suitable for xenogeneic transplantation. Histological examination showed that a total of 50% of the human or duck liver tissue implants survived in the inguinal fat pad of athymic nude mice (BALB/c nu). Histochemical analyses revealed that most hepatocytes transplanted into the fat pad gave positive reactions for glucose-6-phosphatase and with periodic acid Schiff reagent at least 28 days after transplantation. Electron microscopic observation showed that these cells also maintained characteristic cellular organelles. This xenogeneic transplantation into adipose tissue should be useful in the studies on replication and infection of human hepatotropic viruses such as hepatitis B and C viruses. PMID- 1943506 TI - Incidence of spontaneous bacterial peritonitis in patients with ascites. Diagnostic value of white blood cell count and pH measurement in ascitic fluid. AB - During a 21-month period, 65 consecutive patients admitted with ascites were included in a prospective study of the incidence of spontaneous bacterial peritonitis, and paracentesis was performed on admission. The ascitic fluid was cultured, ascitic leucocytes were counted and pH was measured. Bacterial growth was found in five patients with chronic liver disease, who were diagnosed as having spontaneous bacterial peritonitis (SBP), since no intra-abdominal focus could be demonstrated. Thus, the incidence of SBP in this material was 7.7% (95% confidence limits: 2.5-17%). SBP was caused by Escherichia coli (n = 3), coagulase negative staphylococcus (n = 1), and Bacteroides species (n = 1). Abdominal tenderness, abnormal intestinal sounds, fever and hepatic encephalopathy were equally frequent in the group with SBP and in patients with sterile ascites. Infection was not anticipated in any of the patients with SBP. In contrast to several previous studies, neither ascites pH nor ascites leucocyte counts were any help in obtaining a rapid diagnosis. Survival time of patients with SBP was significantly shorter than of patients without SBP. PMID- 1943507 TI - Legal questions surrounding hunger strikes by detainees and prisoners. AB - The 'right to die' is not of an absolute character but is subject to definite qualification. There are legal and social interests reflecting profound ethical values which militate against an absolute right on the part of a prisoner to die by means of a hunger strike. The declared policy of the South African authorities is that a prisoner who resorts to a hunger strike may not be subjected to force feeding. This is in accordance with the 1975 Tokyo Declaration. Unfortunately the Declaration is silent on the question of whether a doctor may provide medical treatment once a hunger striker has reached the point where he is no longer capable of rational thought. In this article it is submitted that a doctor would be legally entitled to do so. PMID- 1943508 TI - Abortion: in search of a constitutional doctrine (Part 2). PMID- 1943509 TI - Medicine and law and industrial torts: an examination of cancer-phobia claims. AB - This article first discusses the elements currently required to support claims for cancerphobia in Louisiana. Second, it addresses some of the medical studies utilized in proving or disproving a claim. Finally, alternative factors are discussed which may be used to determine whether the fear is reasonable where no physical injury is present. PMID- 1943510 TI - Third World birth control--is it abortion? Drug combination gains support as alternative to surgical abortion. AB - Drugs that induce miscarriage may eventually replace traditional surgical abortions in the first three months of pregnancy. In particular, a panel that recently evaluated international drug tests, determined that a specific two-drug combination was safe and effective when used early in pregnancy. The combination included a relatively new compound called RU 486 that induced abortions and has been tested in Europe as a 'morning after' pill. The other drug, prostaglandin, is older, and already on the market. The new twist is that together the drugs can be used as low doses that cause few side-effects, and that in combination, they have approximately a 95 percent success rate in causing abortion during the first three months of pregnancy. Should women be denied this new birth control option on social rather than medical grounds? In most countries cultural, religious and legal considerations will inevitably influence the decision on whether or not to approve RU 486. Concern for women's reproductive health should also be a factor. Moreover, politics should not infringe on sound medical practice, nor should access to a major medical advance be restricted purely on the basis of an emotional debate. PMID- 1943511 TI - The nurse and the law (Part 1). AB - This article examines the legal status of the nurse, the principles of law affecting the nurse's and her employer's liability for negligence, the changing role of the nurse in modern medical practice, the nurse's criminal liability and her role as a witness in court, as well as legal protection, precautions and guarantees against the nurse's personal liability. PMID- 1943512 TI - Hispanics in Chicago: chemical dependency and the law. AB - Due to discrimination, poverty, lack of education and language barriers the recent Hispanic immigrants to the Chicago area have a higher incidence of substance abuse and legal problems than the majority population. In this article a novel treatment approach that deals with these difficulties in a bilingual and socioculturally sensitive milieu is discussed. PMID- 1943513 TI - Prison psychiatry in Japan. AB - This article discusses and provides statistics, on a comparative basis, of crime trends in Japan with special reference to mentally disordered offenders. It also highlights some of the problems experienced by prison psychiatrists. PMID- 1943514 TI - Tightening the reins: recent trend in the application of the insanity defence in Canada. AB - This article gives a critical overview of the Canadian courts' recent pronouncements on the so-called 'insanity defence', irresistible impulse, non insane automatism and the disposition and rights of insanity acquittees. The inconsistencies and conflicts between a number of court decisions relating to section 16(2) of the Criminal Code are highlighted and reform proposals analysed. PMID- 1943515 TI - Planning and the mental health system. AB - This article examines and analyses the difficulties that beset the administration and operation of the Dutch mental health system. In particular, it focuses upon the areas where further improvements in the existing cooperation between the Ministry of Justice and the Ministry of Health could facilitate the care and treatment of mentally ill offenders in the criminal justice system. PMID- 1943516 TI - The history of lupus erythematosus. AB - The history of lupus can be divided into the classical period which saw the description of the cutaneous disorder, the neoclassical period which saw the description of the systemic or disseminated manifestations of lupus, and the modern period which was heralded by the discovery of the lupus erythematosus cell in 1948. PMID- 1943517 TI - The clinical spectrum of SLE. AB - Systemic lupus erythematosus is a complex immunologic disorder with an equally complex clinical presentation and course. In recent years, the earlier recognition of milder disease supported by immunologic markers coupled with means of intervention and suppression, as well as medical/surgical advances has resulted in increases in quality of life and survival. PMID- 1943518 TI - Vascular lesions in SLE. AB - The confusing array of manifestations resulting from multisystem involvement in SLE is due, in part, to the widespread involvement of blood vessels. PMID- 1943519 TI - Autoantibodies and SLE. AB - Systemic lupus erythematosus is characterized by an enormous and increasing array of antibodies to cellular constituents. These autoantibody phenomena are not diagnostic in themselves but must be interpreted within the context of the individual clinical situation. PMID- 1943520 TI - Variants/subsets of SLE. AB - Although systemic lupus erythematosus can be considered a single diagnostic entity, a number of clinical subsets have been described including late-onset lupus, drug-induced lupus, neonatal lupus, discoid lupus, and subacute cutaneous lupus. PMID- 1943521 TI - Management of the pregnant lupus patient. AB - Increased understanding of SLE as it relates to pregnancy has allowed for many women with lupus today to have a successful pregnancy. However, pregnancies are high risk with up to 25 percent ending in miscarriage and with a high frequency of preterm delivery. PMID- 1943522 TI - Medical therapy for SLE. AB - Today, the major therapeutic challenge in systemic lupus erythematosus is to preserve the gains provided by corticosteroids while reducing their side effects. PMID- 1943523 TI - SLE: management overview. AB - Patients with systemic lupus erythematosus can often benefit from cooperative and collaborative interventions prescribed by both physicians and other arthritis health care professionals. PMID- 1943524 TI - A "touch of diabetes". PMID- 1943525 TI - Technology development: protecting our ideas. PMID- 1943526 TI - Theophylline views. PMID- 1943527 TI - Content analysis: reliability and validity. PMID- 1943528 TI - Lactation consultants in the NICU: staff education programs. PMID- 1943529 TI - Intravenous immunoglobulin for neonates. PMID- 1943530 TI - Adapting intravenous pumps for enteral feeding. PMID- 1943531 TI - Infertility ... and new interpretations of pregnancy loss. PMID- 1943532 TI - Treatment decisions. PMID- 1943533 TI - Levonorgestrel subdermal implants (Norplant) for long-term contraception. PMID- 1943534 TI - Detection of Staphylococcus aureus in blood cultures: evaluation of a two-hour method. AB - Aurease--one of three tests on the RAPIDEC staph system for two-hour identification of the main clinically important staphylococci--was used for the direct detection of Staphylococcus aureus from 102 blood culture broths in which Gram-positive cocci were seen. A pellet of centrifuged blood culture broth was used as the inoculum. The method was compared with the thermonuclease test and subsequent isolates subjected to probabilistic identification based on biochemical reactions. A positive aurease test and the presence of thermonuclease were detected in 27 samples, subsequent identification showing all to be Staph. aureus. A further Staph. aureus strain was aurease negative but thermonuclease positive. None of the remaining 74 specimens was positive by the aurease test, which is rapid, sensitive and specific for detection of Staph. aureus in blood culture broths. PMID- 1943535 TI - Recovery of Mycoplasma hominis from blood culture media. AB - Although several workers have demonstrated that Mycoplasma hominis is responsible for 2 to 20% of cases of septicaemia, reports from Britain do not support this premise--possibly because many of the blood culture systems used fail to sustain growth of this organism. Previous work suggests that this is probably due to the inhibitory effects of sodium polyanethol sulphonate (Liquoid) on M. hominis. In an extension of an in-vitro evaluation of blood culture systems, gelatin was shown to give some protection against the inhibitory effect of polyanethol sulphonate on M. hominis. Of 20 systems evaluated, Becton Dickinson's Supplemented Peptone Broth in their Vacutainer collection system was the most successful at recovering M. hominis. PMID- 1943536 TI - Continuous ambulatory peritoneal dialysis: factors influencing recovery of organisms from effluents. AB - In order to establish reasons for a decreased yield of positive culture results from peritoneal dialysates of patients with continuous ambulatory dialysis peritonitis 60 specimens were examined, 47 (78%) of which were positive. A negative result was associated with a delay in processing the specimen and the presence of antimicrobial substances in the dialysate. The application of a method involving dilution of a large volume of effluent in broth did not substantially increase the positive yield. PMID- 1943537 TI - Detection of Chlamydia trachomatis: comparison of agar-gel precipitin test and enzyme immunoassay. AB - The agar-gel precipitation test (AGPT) was compared with Enzyme Immunoassay (EIA) for the detection of Chlamydia trachomatis, 164 women being screened for chlamydial antibodies and antigens in their sera and in endocervical specimens, respectively. The AGPT showed good correlation with EIA in the 164 paired sera and endocervical specimens, resulting in 27 (16.5%) and 22 (13.4%) positive results, respectively (P greater than 0.05). The overall sensitivity of the AGPT compared to EIA was 86.4% (19 of 22), and the specificity was 94.4% (134 of 142). PMID- 1943538 TI - Determination of C reactive protein: an evaluation of three methods. AB - Two semi-quantitative methods--a latex kit and a precipitin test--and a quantitative turbidometric technique were compared to determine the concentration of C reactive protein in serum. Neither of the semi-quantitative tests was found superior in respect of performance or rapidity to the turbidometric method. The cost of capital equipment needed for the latter is high, but it may also be used for a range of other rapid quantitative determinations. PMID- 1943539 TI - Platelet indices: intra-individual variation in pre- and post-menopausal females. AB - Blood platelet counts and mean platelet volumes were determined at weekly intervals for eight weeks in 13 pre-menopausal and 11 post-menopausal females. Samples were analysed exactly two hours after blood collection on a Coulter S plus VTM particle counter. Pre-menopausal platelet counts were slightly higher than post-menopausal counts at each week, but the count was not affected by the menstrual cycle, intra-individual variation showing mean coefficients of variation (CV) of 7.4% and 5.2% respectively. The mean platelet volume was similar in pre- and post-menopausal groups at each week and showed little variability over time (mean CV 2.7% and 3.3%, respectively). Platelet parameters show little variability over time in either group and with no cyclical effects of menstruation apparent. PMID- 1943540 TI - Detection of toxoplasma-specific immunoglobulin-G: assessment of a slide agglutination test. AB - The performance of a slide agglutination test for detection of toxoplasma specific IgG was assessed and compared with that of the dye test and latex agglutination test. The slide agglutination test was as sensitive as, and more specific than, latex agglutination. The predictive value of a negative slide agglutination test was less than the latex agglutination test but produced results within minutes, although quantitative results were not comparable to other assays. Slide agglutination presents a rapid alternative to the latex agglutination test as a screening assay for toxoplasmosis, although patients at risk of life-threatening infection require detailed serological examination using additional methods. PMID- 1943541 TI - Tissue banking: the role of the Regional Blood Centre: an American experience in Minnesota. AB - The clinical use of bone, cornea, skin, connective tissue and heart valve allografts has increased greatly in the past several years, with bone the most commonly transplanted tissue. Tissue allografts have been the vehicle to transmit infectious disease from donor to recipient. Provision of safe and effective tissue has gradually developed and improved as regional tissue banks have organized, and standards of practice evolved. Regional Blood Centres have the special capabilities and experience to provide the expertise required in tissue banking. Consequent to these community needs, regional bone and tissue banks have been established in blood banks and the experience of the American Red Cross in St Paul, Minnesota is described. PMID- 1943542 TI - Automated haematology analysers. PMID- 1943543 TI - A rapid test to detect the most clinically significant Staphylococcus species. AB - A new two-hour test system (RAPIDEC staph) to detect the main staphylococci was evaluated. Of 124 reference strains tested, 83 represented species most often found in clinical specimens, the remaining 41 strains representing five species primarily of animal origin. RAPIDEC staph detected all Staph, aureus, Staph. epidermidis and seven of eight Staph. saprophyticus strains. Of the animal species, all Staphylococcus intermedius strains were assigned to the correct category, the remainder were misidentified as Staph. epidermidis. With 121 catalase-positive Gram-positive cocci isolated from urines the test system correctly detected all Staph. aureus strains, 39 of 41 Staph. epidermidis, and 34 of 36 Staph. saprophyticus. Of 25 atypical Staph. aureus strains which were either slide or tube coagulase negative the test system correctly detected all 17 slide coagulase negative strains but failed to detect eight which were tube coagulase negative. There were no false positives. RAPIDEC staph is a rapid, accurate system for the detection of the three main clinically important species of staphylococci. PMID- 1943544 TI - [Factor analysis of the results of combined clinico-radiological examination in thyroid diseases]. AB - The paper is concerned with factor analysis data on the results of combined radioclinical investigation in thyroid diseases. A program including 111 parameters in 291 patients (anamnestic data, results of physical examination, palpation of the thyroid and the neck region, scannographic, thermographic, and ultrasound symptoms, indicators of radiometry and in vitro tests) was developed at the IBM Company. This method was employed for obtaining objective information on the diagnostic value of each method as well as for detecting certain symptoms of the greatest diagnostic importance in different nosological entities of thyroid diseases. PMID- 1943545 TI - [Carcinoembryonic antigen and immunity in breast cancer]. AB - Three groups of breast cancer patients were investigated: with a high level of CEA, with a lowered level of CEA, and those in whom CEA was undetectable either before or after therapy. The relationship of the time course of blood CEA, nonspecific body reactivity, and radiotherapeutic efficacy was established. Ineffective radiotherapy resulted in inhibition of phagocytic activity of blood neutrophils and cell stromal reactions at a tumor bed against a decrease in CEA concentration as compared to the basal levels in patients. Effective radiotherapy led to increased CEA levels, phagocytic activity was unihibited and slightly on the decrease. A considerable effect of the a CEA level on the T-system of immunity was unnoticed. In the group with the absence of blood CEA, there was an increase in the phagocytic activity of blood neutrophils and cell stromal reactions in a tumor against a background of a higher ability of lymphocytes to a spontaneous blast transformation reaction and a lesser decrease in the T lymphocyte count that in the other groups. PMID- 1943546 TI - [Diastolic function of the left heart ventricle in patients after myocardial infarct]. AB - Altogether 129 patients were investigated 3 months after the onset of myocardial infarction (MI). Left ventricular diastolic function was assessed using a set of parameters of radionuclide ventriculography, including fractions of filling of the first and second thirds of the diastole, increments of volumes in the phases of fast and slow filling, a maximum rate of filling and the time of achieving it. Marked disorders of isovolumetric relaxation (indices of filling of the first third of the diastole) as well as changes of volumetric compliance (a ratio of increments of volumes of filling of the first and second thirds of the diastole) were revealed in the patients. A degree of disorder of left ventricular diastolic function and MI localization showed no correlation, however more noticeable changes were observed in the group of patients with the anterio-apical localization of myocardial lesion as compared to patients with lesions of posterior-lateral localization. PMID- 1943547 TI - [Quantitative assessment of morphologic changes in tumors during combined use of irradiation, induced hyperglycemia and local hyperthermia]. AB - The paper is concerned with morphometric evaluation of changes in Ehrlich mouse solid carcinoma after a separate, dual and combined use of x-ray irradiation, induced hyperglycemia (IH) and local hyperthermia (HT), using two-staged quantitative analysis of tumor tissue injuries. A portion of viable tissue was determined at the first stage, and the density of location of undestroyed tumor cells was evaluated at the second stage. The general result was characterized by the product of these indices. Disorders in the tumor tissue structure were noted in 24 h, the main damage being done by IH and HT in the center of a tumor. In 48 h the total effect was on the increase only in groups with irradiation as a result of cell death in the peripheral zone. In the double use of the agents their combined effect was less than the additive one, and the combined use of all three methods resulted in obvious synergism, and the number of viable tumor cells (by morphological criteria) was decreased by more than two orders. PMID- 1943548 TI - [Distant radiotherapy in rheumatoid arthritis]. AB - During an open controlled study of 20 patients with rheumatoid arthritis (resistant forms) their lymph nodes were irradiated at a dose of 7.5 Gy. Clinical improvement, including reduced morning rigidity, the number of inflamed joints, and Riccis index, was noted shortly after therapy and 6 mos. after irradiation in 50% of the patients. Immunosuppression and moderate lymphopenia were noted in all of them. Of the side-effects there was nausea that disappeared without additional treatment. A conclusion has been made that irradiation of the lymph nodes at a total dose of 7.5 Gy is equally effective but less toxic than irradiation of 20 Gy. PMID- 1943549 TI - [Dynamics of rheological properties of the blood in patients with breast cancer during combined treatment]. AB - The paper is devoted to the results of investigation of blood rheological features (dynamic blood and plasma viscosity) in 70 breast cancer patients during combined therapy. The basal levels of dynamic blood viscosity indices in these patients were lower by 11.6% than in the control group of healthy women (p less than 0.05). During combined therapy after a course of gamma-beam therapy (in the small fractionation regimen for the 1st group and large fractionation regimen for the 2nd group) a further decrease of blood and plasma viscosity indices was observed, reaching their minimum values on the 14th day after radical mastectomy. In a long-term period of combined therapy (5 years--the 3rd group) dynamic blood and plasma viscosity indices remained below the control values and had no significant differences from the basal values in the 1st and 2nd groups. These shifts in rheological blood features during combined therapy of breast cancer were probably of favourable nature as complications (hypostatic pneumonia, thromboses, necroses of displaces of skin grafts) in the postoperative period were absent. PMID- 1943550 TI - [Results of a follow-up of participants in the liquidation of the effects of the Chernobyl AES accident]. AB - The paper is concerned with the results of analysis of a clinico-laboratory study of persons (residents of Armenia) who took part in the elimination of the effects of the Chernobyl accident. Investigation of general morbidity revealed no correlation with exposure to ionizing radiation. The symptom complex of pathological changes included CNS functional disorders, a transition from the hypokinetic type of a heart response to exercise to the normokinetic one, lowered immune status and tissue peripheral blood flow, unmarked hematological and biochemical shifts, suggesting suppression of the body antioxidant system. PMID- 1943551 TI - [Radiation-protective action of a gas mixture containing 8% of oxygen in single and fractionated local irradiation of the kidneys]. AB - The protective action of a hypoxic gaseous mixture, containing 8% of oxygen was studied in a long term after local single and fractionated irradiation. A degree of protection of all morphofunctional structures of the kidney, evaluated by different criteria, was approximately the same (1.25-1.33). Dose fractionation into 5 fractions caused no considerable changes in DMF of hypoxia. PMID- 1943552 TI - [Roentgeno-ultrasound diagnosis of acute pancreatitis and its complications]. AB - A program of combined radio-ultrasound diagnosis of acute pancreatitis was developed. Altogether 1257 patients were investigated over time, of them various complications were found in 303 (24%). The accuracy of detection of acute pancreatitis was 92%, that of purulent complications was 93%, that of false pancreatic cysts was 98.2%. Ultrasound and roentgenological semiotics of various types of complications of pancreatitis was described. Ultrasound investigation was shown to be the most important one in the diagnosis of patients with acute pancreatitis. PMID- 1943553 TI - [Unilateral expansion of the lung root in a radiogram or fluorogram]. PMID- 1943554 TI - [A single pulmonary node]. PMID- 1943555 TI - [Automated subsystem of recording and analysis of data on individual dosimetric control]. AB - An automated data bank of individual dosimetric control using Electronika MS 0507 microcomputer has been developed and is being tested now. The bank provides for data acquisition and processing, registration of the professional status of personnel, calculations, automated archives, and printing of documents. Radiation control data, accumulated at the data bank, were used to determine approaches to control a radiation situation by correcting parameters of a technological process. PMID- 1943556 TI - [Dosimetric planning of partial radiation exposure in radiobiological experiments]. AB - The authors describe a new method of dosimetric design of partial radiation exposures (PRE) in radiobiological experiments on rodents, using a universal lead component screen. A choice of a shape of irradiation fields and location of screen elements on the body of an animal is done according to a CT program, developed in the IBM PC version. This method helps to standardize physicotechnical support of PRE in radiobiological experiments. PMID- 1943557 TI - [Computer analysis of the contours of the large intestine for the purpose of disease diagnosis]. AB - The authors put forward a new method of structural analysis of images, based on an automatic search for regularities of signs of colonic diseases in the shape of contours of colonic segments. The regularities obtained were used as diagnostic signs. The results of analysis of the shape of contours of the 1st (cecum and the ascending colon) segment and the 5th (the rectum) segment in 83 patients. The results of CT diagnosis coincided with verified clinical conclusions. PMID- 1943558 TI - [Evaluation of conditions of radiation protection of medical personnel during intracavitary neutron therapy of cervical cancer]. AB - Combined radiation therapy was provided to 106 cervical cancer patients. Endostats and sources of neutron radiation 252Cf of low activity were administered manually. Working conditions of the personnel were examined, the rate of exposure doses and flows of neutrons at working places were measured, dose exposures of the personnel were evaluated. It has been concluded that occupational conditions for the medical personnel are considered to be relatively safe. PMID- 1943559 TI - [Radiation dosage]. PMID- 1943560 TI - [Densitometric indices of the lungs and mediastinum in normal state according to computerized tomography data]. PMID- 1943561 TI - [Radionuclide ventriculography in the evaluation of the diastolic function of the left heart ventricle]. AB - A maximum filling rate (FRmax), the time of reaching it (T-FRmax), the fraction of filling of the first and second diastolic thirds (FF1/3 and FF2/3), an increment of the volume in the first and second diastolic thirds (delta V1 and delta V2) were investigated on the basis of radionuclide ventriculography findings, 99mTc being used. CHD patients (n = 133) were characterized by a decrease in FF1/3, FRmax, an increase in T-FRmax changes in the ratio of delta V1 and delta V. A normal filling process was characterized by predominance of filling in the first diastolic third (the fast filling phase - delta V1 greater than greater than delta V2). Left ventricular diastolic dysfunction was characterized either by a homogeneous distribution of filling in the phase of fast or slow filling with practically equal increasing of volumes in the first and second diastolic thirds (delta V1 = delta V2) or by shifted filling during diastasis (delta V1 less than delta V2). PMID- 1943562 TI - [Prognostic problems in the oncology clinic]. AB - The purpose of this paper is to consider a number of biological and clinicomorphological signs of human tumors which influence the prediction of a course of disease as well as prognosis of a tumor response to radiation exposure. Analysis of the literature has shown that some factors of quite a favourable course of a tumor process are likely to be the signs of clinical radioresistance of the tumor. A strong possibility of individual prognosis of a tumor response to radiation therapy was shown for oropharyngeal and stomach tumors even at its onset, guided by change in the level of their proliferative activity, determined with an indirect immunofluorescent rapid method. The probability of detecting tumors, which are clinically radioresistant to proposed therapy, is 82.4-95%. PMID- 1943563 TI - [Cytological methods in predicting the degree of the direct effect of radiation exposure]. AB - A study was made of the cytological criteria of various degrees of radiation pathomorphosis of soft tissue cancers and sarcomas in different dose fractionation regimens and varying time of a preoperative interval. Combinations of the main and additional parenchymatous and stromal cytological signs, reflecting pathomorphosis of I-IV degrees were singled out. Schemes of cytological prediction of a direct effect of tumor radiation exposure were drawn up on the basis of regularities of changes in cellular pictures, obtained from diagnostic data before irradiation. PMID- 1943564 TI - [The histological characteristics of human lung tumor transplants growing under the renal capsule of mice in an immunodepressed state]. AB - In order to determine the prognostic value of a "subcapsular test" in assessment of individual sensitivity of lung tumors to antitumor action, research was conducted into the histological structure of 18 human lung tumors and 110 grafts of these tumors, which had grown within 6 days under the renal capsule in mice under the immunosuppressed condition, caused by whole-body irradiation. The presence of necrosis in an original tumor led to connective tissue growth in grafts. The stroma/parenchyma ratio in grafts was increased as compared to original tumors. Lymphoid infiltration in 6-day grafts was, as a rule, unmarked. In 2 of 18 cases histotypes of a primary tumor and its grafts differed, i. e. the "subcapsular test" could be used to detect latent polymorphism of lung tumors. Correct prognosis of an individual response of human lung tumors to antitumor action with the "subcapsular test" also necessitated histological verification of the results. PMID- 1943565 TI - [The effect of preoperative radiation therapy on the results of the combined treatment of esophageal cancer]. AB - The authors resorted to multifactor comparative analysis of the results of surgical (218) and combined (413) treatment of patients with thoracic esophageal cancer to study the interrelationship of the main factors, determining a cancer stage, their prognostic value, and a degree of influence of preoperative modalities on these factors. Preoperative irradiation was shown to increase resectability of the esophagus with tumor extent over 5 cm and to improve the prognosis of disease. PMID- 1943566 TI - [The digital processing of tomograms in the diagnosis of peripheral lung cancer]. AB - The paper is devoted to the description of the methods and results of digital processing of linear tomograms of the lungs in 347 patients with "small" lesions (2 cm in diameter in 67%), densitometry of abnormal lesions was performed in 167 of them. Roentgenomorphological comparisons were done in 326 cases, where diagnosis was verified at operation. Digital processing of images and densitometry provided additional diagnostic information. The diagnostic accuracy of the proposed method for lung cancer was 92%. PMID- 1943567 TI - [Radioimmunological analysis in assessing the function of the hypothalamo neurohypophyseal system in patients with hypothalamic syndromes]. AB - Assessment of vasopressin by radioimmunoassay has shown an increase in its blood concentration and a disturbed reaction of the vasopressinergic structures of the hypothalamus to metoclopramide, furosemide, insulin hypoglycemia, and exercise. Functional tests with the dopaminergic drug bromocriptine and antiserotoninergic drug cyproheptadine help to make an individual choice of the most effective drug for therapy of the hypothalamic syndrome of neuroendocrine-metabolic type. The patients can be divided into sensitive to either the first or the second drug of both which is important for adequate pathogenetic therapy. PMID- 1943568 TI - [An evaluation of the efficacy of radiation and surgical treatments in tumors of the paranasal sinuses and nasopharynx by using computed tomography]. AB - A total of 40 patients with benign and malignant paranasal sinusal and nasopharyngeal tumors were examined to evaluate the effectiveness of radiation and surgical treatment with the help of computerized tomography (CT). The aim of CT examinations was to reveal CT findings of radiation pathomorphosis of a tumor mass and contiguous tissue, to determine their CT structure, and to find residual masses after the treatment. CT findings of three stages of tumor radiation pathomorphosis were determined. Besides, sings of a radiation reaction of the paranasal sinusal mucosa and consequences of cerebral radiation necrosis were described. Some criteria of objective assessment of the results of radiation and surgical treatment of paranasal sinusal and nasopharyngeal tumors were proposed. PMID- 1943569 TI - [The effect of the radiochemical purity of 123I-sodium iodide on the absorptive function of the thyroid]. PMID- 1943570 TI - [The morphological characteristics of sarcoma M1 cells before and after irradiation]. AB - Morphology of the death of rat sarcoma M1, cells before and in varying time after irradiation at doses of 10 and 20 Gy with and without metronidazole (as a radiosensitizer) was investigated at the light optic and electron microscopic levels. Two types of death: necrosis and apoptosis with the prevalence of the former were revealed. Irradiation and the use of metronidazole did not influence the type of death of sarcoma M1 cells. PMID- 1943571 TI - [The ultrasonic control of the function of the bile-secreting system during extracorporeal lithotripsy]. PMID- 1943572 TI - [A space-occupying formation in the area of the lesser pelvis (in women)]. PMID- 1943574 TI - [Studies on the terminology of radiation therapy]. PMID- 1943573 TI - [The pre-radiation preparation of cancer patients]. PMID- 1943575 TI - [The pathogenesis of radiation-induced sclerosis]. PMID- 1943576 TI - [The current state of physicotechnical and mathematical support for plane scintigraphy]. PMID- 1943577 TI - [Local electromagnetic hyperthermia in treating patients with chronic prostatitis]. AB - Local electromagnetic hyperthermia (LEH) was applied to 29 patients with nonspecific chronic prostatitis, using UHF-units Plot or Yakhta-3 (915 MHz). Heating was achieved with the help of intracavitary areals via the rectum. A therapeutic course consisted of 6-10 LEH sessions. A direct positive clinical effect was observed in all the patients after the LEH course was over. Prostatic secretion indices returned to normal in 25 patients; a moderate leucocyte count was found in 4 patients only. Exacerbation of disease was noted in 3 patients in the course of the first year after therapy. They were given a repeated LEH course, which brought about a positive effect. Potency in 14 patients (8 of 10 with decreased potency and 6 with normal potency) was increased after LEH. LEH seems to hold promise for therapy of chronic prostatitis and its consequences. This method results in no complications, therefore LEH courses can be repeated in case of exacerbation. PMID- 1943578 TI - [Possibilities and limitations of isoeffective models in the assessment of the equivalence of courses of fractionated irradiation]. AB - The authors present radiobiological substantiation of empiric isoeffective formulae and cell-kinetic models. They discuss in a comparative aspect the potentialities and limitations of these formulae and models for calculation of tolerant doses to normal tissues for various courses of fractionated irradiation. It has been unestablished which isoeffective model predicts most adequately tolerant doses to regimens with daily dose fractionation and unclassical dynamic schemes of dose fractionation. PMID- 1943579 TI - [Results of the treatment of cancer of the movable part of the tongue with clinically intact regional lymph nodes]. AB - A study was made of the frequency of metastatic spreading to the regional neck lymph nodes and long-term results of therapy of 126 patients with cancer of the movable part of the tongue with clinically intact regional lymph nodes of the neck. With regard to an employed modality (irradiation, alone and in combination with surgery, surgery and observation) the frequency of metastatic spreading to the neck lymph nodes was 20, 7, 17, and 34%, respectively, and 22% for the whole group. The 5-year survival rates were 79, 50, 49, and 67%, and 61% for the whole group. The main cause of death in 40% of the patients was a primary tumor recurrence versus 17% following the other modalities. PMID- 1943580 TI - [Clinical assessment of various methods of radio-modification in radiotherapy of advanced oropharyngeal cancer]. AB - The purpose of the study was to evaluate the effectiveness of RF-hyperthermia and regional intraarterial hyperglycemia as adjuvant radiotherapy vs conventional radiotherapy of advanced head and neck cancers. Altogether 115 patients with advanced T3-T-4 carcinoma of the tongue, oral cavity and oropharynx underwent external radiotherapy (Co-60). An RF capacitative heating device operating at 40.68 MHz was employed twice a week, a total of 4 sessions per patient. Intratumor temperature was 41.5-43 degrees C. Hyperglycemia was performed via the branches of the carotid artery, a total of 3 sessions per patient. There were 4 groups (1-31 patients on conventional radiotherapy; 2-24 patients on thermoradiotherapy; 3-30 patients on radiotherapy plus regional hyperglycemia; 4 30 patients underwent combined radio-modification). A complete response was 29% for conventional radiotherapy, 67% for thermoradiotherapy, 60% for radiotherapy plus hyperglycemia, and 77% for combined radio-modification. A 2-year local control was found to be 13% for radiotherapy, 37% for thermoradiotherapy, 17% for radiotherapy plus hyperglycemia, and 35% for combined radio-modification. Only hyperthermia was found to improve a 2-year local control of advanced oropharyngeal cancer. PMID- 1943581 TI - [Radiation pathomorphosis in intensive preoperative hypoxic radiotherapy of stomach cancer]. AB - The authors presented the results of pathomorphological investigations of surgical specimens of 110 stomach cancer patients following preoperative radiotherapy or hypoxyradiotherapy and radical operation. Single and total focal doses depended on oxygen percentage in the inhaled mixture and were 4-5 and 20-25 Gy, respectively. Radiation pathomorphosis was established in 62.8% of the patients (in 19.1% it was marked, in 13.5% it was absent, unclassified changes were noted in 23.6%). Short-term hypoxia resulted in no tumor "protection". Radiation changes in the stomach mucose in hypoxyradiotherapy were noted 2-3-fold less frequently than in radiotherapy, suggesting predominant "protection" of healthy tissues by hypoxia. PMID- 1943582 TI - [Radionuclide study of blood flow in tumor and normal tissues of rats in induced hyperglycemia]. AB - Radionuclide angiography was performed in rats with transplantable tumors (sarcoma 45 and Walker carcinosarcoma 256). Induced hyperglycemia was shown to result in blood flow inhibition in tumor and normal tissues of tumor-bearing rats. Some differences were revealed in a degree of reversibility of blood flow disorders in tissues of the above strains. The results obtained confirmed the advisability of radiation therapy at the height of a decrease in tumor blood flow. PMID- 1943583 TI - [Primary lymphosarcoma of the bones]. PMID- 1943584 TI - [An experimental study of tumor-tropic properties of radionuclide-labeled liposomes]. AB - The paper is concerned with the results of experimental investigations to develop methods for obtaining 99mTc and 67Ga-labeled liposomes, possessing tumor-tropic properties. Sphingomyelin vesiculae, labeled with 67Ga with the help of bifunctional chelates, were shown to possess a high level of hyperfixation. A study of biodistribution of these liposomes in rats with Plis lymphosarcoma showed that the level of accumulation of 67Ga-liposomes was enough to obtain a clear scintigraphic tumor image. PMID- 1943585 TI - [Dynamic scintigraphy of the kidneys using lasix]. AB - Dynamic scintigraphy with lasix (urosemide) in 59 patients with hydronephrosis, nephrolithiasis, chronic pyelonephritis, ureterohydronephrosis on an initial scintigram has shown retention of 99mTc-DTPA in the urinary tracts: an increase or absence of the excretory segment on the activity-time curve up to the appearance of an obstructive type of a curve. Verified operative findings in 19 patients with hydronephrosis and nephrolithiasis have shown a high sensitivity and accuracy of the detection of stenosis of the urinary tracts in the absence of the excretory segment on an initial scintigram irrespective of the fact whether it appears or not on a scintigram after lasix administration. Stenosis of the ureteropelvic segment can be observed in the presence of the excretory segment on an initial scintigram with a prolonged half-period of RP excretion; its 2-fold decrease is noted on a scintigram after lasix administration. PMID- 1943586 TI - [Role of transvesical ultrasonic scanning in the diagnosis of causes of ureteral stenosis in patients with cervical cancer]. AB - gamma-Beam therapy of combined radiation therapy are frequently followed by ureteral obstruction, caused by a cervical cancer recurrence or pelvic postradiation fibrosis. The knowledge of a cause is very important for a choice of therapeutic tactics of obstructive uropathy. The purpose was to define the potentialities of transvesical ultrasound scanning (TVUSS) in order to reveal causes of disturbed urodynamics of the urinary tracts after radiation therapy of cervical cancer. TVUSS was performed in 17 women with a confirmed diagnosis. It turned out that a cervical cancer recurrence could be differentiated from postradiation fibrosis by specific ultrasound signs. Another group of 44 patients was investigated using this method to find out causes of disturbed urodynamics of the upper urinary tracts: postradiation pelvic fibrosis was noted in 7 patients, a recurrence of cervical cancer--in 19, a recurrence of cervical cancer with the involvement of the urinary bladder--in 11, and bladder carcinoma--in 3, in 3 other cases the diagnosis was not established as a result of difficulties in interpreting sonograms. PMID- 1943587 TI - [Acute abdomen]. PMID- 1943588 TI - [Acute intestinal obstruction]. PMID- 1943589 TI - [Diagnosis of autonomic-vascular dystonia in persons who participated in the liquidation of the effects of the Chernobyl AES accident]. AB - The diagnosis of autonomic-vascular dystonia caused by small doses of ionizing radiation can be made only on the basis of the objectivity, completeness, constructive and individual character of data. It gives an opportunity to reflect in the diagnosis cause/effect relationships, to define the main and supplementary factors of a pathological process and to show their interrelationships and interinfluence. It leads to the development of adequate therapeutic rehabilitation tactics. PMID- 1943590 TI - [Radiobiological aspects of "hot" particles]. PMID- 1943591 TI - [Bone marrow tissue doses in various types of radiation exposure]. AB - Basing on some literature data and their own results, the authors calculated bone marrow radiation doses in global fallouts, medical x-ray investigations, a radionuclide fallout during the Chernobyl accident, and under occupational conditions during exposure to radiation factors of luminous compounds of permanent action (LCPA). Functional insufficiency of hemopoiesis and the absence of synchronization in bone marrow and peripheral blood responses to radiation exposure were revealed in professionals, working in contact with LCPA in correlation with doses of external inhomogeneous gamma-beam irradiation. PMID- 1943592 TI - Interviewing tips for the 90's nurse. PMID- 1943593 TI - [The sociopsychological characteristics of women who suffer from alcoholism and who have committed illegal actions]. PMID- 1943594 TI - [Care of the hair]. PMID- 1943595 TI - [The general assessment of a patient's respiratory status]. PMID- 1943596 TI - [The basic types of electrocardiostimulators]. PMID- 1943597 TI - [Ichthyosis]. PMID- 1943598 TI - [Endometriosis]. PMID- 1943599 TI - [The care of patients with maxillofacial trauma]. PMID- 1943600 TI - [The climacteric syndrome]. PMID- 1943601 TI - [Vaginismus]. PMID- 1943602 TI - [Diet No. 9B (winter-spring)]. PMID- 1943603 TI - [The birch]. PMID- 1943604 TI - [The reasons for a deficiency of specialists with a paramedical education]. PMID- 1943605 TI - [The polishing and checking of the skill of intravenous drug administration]. PMID- 1943606 TI - [The performance of regional lymphotropic therapy by nurses. Drug interactions]. PMID- 1943607 TI - [The factors that determine the quality of medical care]. PMID- 1943608 TI - [Methodological recommendations for the organization of centralized sterilization departments in treatment and prevention institutions]. PMID- 1943609 TI - [Problems in planning the graduation of paramedical personnel, their training and work organization]. PMID- 1943610 TI - [Methodological recommendations on the organization of centralized sterilization departments in treatment and prevention institutions]. PMID- 1943611 TI - [A healthy life style--the path to longevity]. PMID- 1943612 TI - [Assessing the psychological and social status of the patient]. PMID- 1943613 TI - [The system of zero-defect work for outpatient clinic nurses]. PMID- 1943614 TI - [The treatment of the climacteric syndrome]. PMID- 1943615 TI - [Medical gymnastics in the rehabilitation of children and adolescents with enuresis]. PMID- 1943616 TI - [Measures for the creation of aseptic conditions in units for patients with a profound depression of immunity]. PMID- 1943617 TI - [The basic diet]. PMID- 1943618 TI - [Centaurea]. PMID- 1943619 TI - [Mercy as the essence of the nurse's work]. PMID- 1943620 TI - Etiologic factors associated with patellofemoral pain in runners. AB - The purpose of this study was to extend our knowledge of running related injuries by determining whether relationships exist between selected anthropometric, biomechanical, muscular strength and endurance, and training variables and runners afflicted with patellofemoral pain (PFP). Specifically, the objectives of this study were to examine differences in selected measures between a non-injured control group (C) of runners (N = 20) and a group of injured runners (INJ) diagnosed by an orthopedic surgeon as having PFP (N = 16). High speed photography, a force platform, and isokinetic dynamometry were used to determine rearfoot motion, ground reaction forces, and knee muscular strength and endurance. Stepwise discriminant function analyses were performed on the anthropometric, biomechanical, and muscular strength and endurance variables. Q angle was a significant discriminator (P less than 0.01) between the INJ and C groups. The muscular endurance data revealed several significant discriminators with the INJ subjects being weaker in knee extension endurance. Kinetic analysis revealed several significant discriminators whereas rearfoot movement variables were not good discriminators between the groups. The training data revealed that the INJ group ran significantly less (P less than 0.01) miles.wk-1 than the C group. Our results suggest that Q angle is a strong discriminator between runners afflicted with PFP and non-injured runners. In addition, several muscular endurance and kinetic variables may also be important components of the etiology of PFP. PMID- 1943621 TI - Hemodynamic responses to 6 degree head-down rest in dogs: effect of aerobic conditioning. AB - The -6 degree head-down position is used in humans to produce fluid shifts that resemble those occurring in microgravity. Alternative animal models of microgravity may be helpful for extensive exploration of this unique condition. The dog may be a viable candidate. Sixteen dogs were assigned to one of three conditions: anesthetized open chest, anesthetized closed chest, and awake. Dogs in groups 1 (N = 6) and 2 (N = 6) were divided into an exercise or a sedentary treatment, and dogs in group 3 (N = 4) served as their own controls. Following instrumentation the dogs were put in the head-down position for 1 h. Measurements included right atrial pressure, heart rate, and mean arterial pressure for all groups, left ventricular pressure and LV dp/dt for group 1, and cardiac output and iliac flow for group 2. Right atrial pressure increased for all groups. Heart rate demonstrated non-significant changes over time or group. Significant differences were noted for mean arterial pressure, left ventricular pressure and LV dp/dt for exercise condition in response to HDR. It appears that -6 degrees of head-down rest produces similar cardiovascular responses in dogs as those observed in humans and that exercise has a minor effect on those responses. PMID- 1943622 TI - Plasma creatine kinase activity and exercise-induced muscle damage in older men. AB - Plasma creatine kinase (CK) activity has often been used as a marker of exercise induced skeletal muscle damage. While the pattern of muscle damage following eccentric exercise has been established in young adults, there is little data available on eccentric exercise-induced muscle damage in older individuals. The purpose of this study was to compare ultrastructural changes in skeletal muscle following high intensity eccentric exercise of young and older men and to determine whether CK activity is a reliable predictor of muscle damage. Five young (20-30 yr) and five older untrained men (59-63 yr) performed three 15-min bouts of eccentric exercise at 90, 80, and 70% of maximal concentric power output. There was a prolonged increase in CK up to 10 d following exercise that was not significantly different between groups. Light and electron microscopic examination of needle biopsies obtained from the vastus lateralis showed evidence of focal damage in greater than 90% of the post-exercise fibers examined in the older subjects, compared with values ranging from 5 to 50% reported previously in young subjects. Quantitative analysis using light microscopy showed greater damage in the older subjects than reported previously in young subjects. These data suggest that older adults experience greater muscle damage following eccentric exercise than young subjects, which may be due in part to the smaller muscle mass and lower VO2max seen in older men. In addition, there was no relationship between CK activity and the corresponding amount of muscle damage observed in each subject, suggesting that CK activity may be a poor predictor of exercise-induced muscle damage. PMID- 1943623 TI - Transfer effects of endurance training with the arms and legs. AB - The purpose of this study was to examine whether endurance training in the form of arm or leg cycling resulted in significant transfer effects when exercise was performed with the untrained muscle group. Sixteen middle-aged male volunteers completed 24 training sessions over 8 wk on either an arm cycle ergometer (AG, N = 8, mean age = 35.2 +/- 6.6 yr) or a leg cycle ergometer (LG, N = 8, mean age = 41.0 +/- 4.7 yr). The two groups were initially equated for their pre-training peak oxygen uptake (pVO2) determined during leg cycling (44.5 +/- 5.0 and 43.8 +/ 7.7 ml.kg-1.min-1 for the AG and LG, respectively). Training was performed at an intensity that was mid-way between the pre-training ventilatory threshold (VT) and the pVO2 for both cycling methods. Significant increases (P less than .05) were observed in the relative values of the oxygen uptake at the VT and the pVO2 as a result of both these methods of training, but these elevations were specific to the muscle groups that were trained. This specificity of training was also evident in the cardiorespiratory and metabolic measurements obtained during submaximal steady state exercise performed at the power output corresponding to the pre-training VT during arm and leg exercise. Hence, it was concluded that improvements in exercise performance resulting from short-term aerobic training with the arms or legs in middle-aged males with relatively high aerobic powers are due primarily to peripheral adaptations in the trained muscles. PMID- 1943624 TI - Changes in muscle fiber size and composition in response to heavy-resistance exercise. AB - Progressive resistance exercise was used to induce hypertrophy in the right palmaris longus muscle (PLM) of 16 cats. The left PLM served as the non-exercised intra-animal control. After an average 150 +/- 26.6 wk of training, left and right PLMs were removed and weighed. Muscle fibers were typed using standard histochemical techniques. Mean fiber cross-sectional area, connective tissue content, and muscle fiber length were determined. The right exercised PLM demonstrated a 24.2 +/- 6.9% increase in muscle mass. Mean muscle fiber cross sectional area increased 11.0 +/- 7.3% in the exercised muscles. No change in connective tissue content, fiber length, or fiber type composition was observed. The results show that increases in muscle fiber cross-sectional area do not account for all the observed increases in muscle mass, and that other mechanisms, such as muscle fiber hyperplasia, may play a role in contributing to muscle mass increases. PMID- 1943625 TI - Psychophysical power functions of exercise limiting symptoms in coronary heart disease. AB - Thirty consecutive male patients with angiographically determined multivessel disease and ten healthy volunteers were subjected to a symptom limited exercise test with stepwise increments of 10 W every minute. Leg exertion, breathlessness, and chest pain were rated according to a category-ratio scale with 10 degrees and psychophysical power functions computed. Depending on whether chest pain was the limiting symptom, patients were subdivided into groups A (N = 20) and B (N = 10). Exercise capacity did not differ between groups A and B. Both groups terminated the exercise test at lower work loads and lower symptom intensities than the healthy volunteers. Psychophysical power functions were similar for leg exertion in the three groups while the growth of breathlessness was lower in group B. In group A the intensity of chest pain increased more rapidly than leg exertion or breathlessness. In conclusion, those patients with coronary heart disease interrupt the exercise test at lower ratings of leg exertion and breathlessness than healthy volunteers. The psychophysical power functions do not grow more rapidly for these sensory modalities in patients than in healthy volunteers. PMID- 1943626 TI - Psychobiologic effects of 3 d of increased training in female and male swimmers. AB - Eighteen female and 22 male college swimmers completed a paced 182.9 m swim before and after a 72 h period of increased training. Training volume was increased from 6,800 to 11,200 m.d-1 for the females and from 8,800 to 12,950 m.d 1 for the males. Salivary cortisol, heart rate, stroke mechanics, as well as overall and local ratings of perceived exertion (RPE) were measured in conjunction with the two swim tests. Mood states, as measured by the Profile of Mood States, and ratings of perceived muscle soreness were assessed daily. Significant (P less than 0.005) elevations in stroke frequency, overall and local RPE, fatigue, overall mood, and muscle soreness levels occurred in association with the increased training. Significant (P less than 0.005) reductions in vigor and stroke length were also observed as a consequence of the greater training load. The main effects for gender and the gender by trial interactions were not significant for each variable tested. It was concluded that: 1) affective, biomechanical, and perceptual variables are sensitive to a 3 d increase in the volume of swim training, 2) heart rate and cortisol levels are not influenced by the type of increased training employed in this study, and 3) female and male college swimmers do not differ in their psychological or physiological responses to a rapid increase in training volume. PMID- 1943627 TI - Dynamic performance assessment of selected sport shoes on impact forces. AB - Few investigators have evaluated the performance characteristics of non-running sport shoes. The purpose of this study was to assess the dynamic performance characteristics of four different shoe models during landings. Five male subjects performed 25 voluntary hanging drop landings (60 cm) onto a force platform (1000 Hz) for each of four shoe conditions (C1 and C2 = basketball shoe, C3 = running shoe, C4 = volleyball shoe). Ground reaction force data were evaluated for maximum forefoot (F1) and rearfoot (F2) impact forces as well as the respective times of occurrence of these events (T1, T2). Results of the group data analysis indicated a preferential performance rank order of C1, C3, C4, C2 although significant interaction effects were observed, indicating a need for single subject analyses. Three techniques were incorporated to assess individual subject condition differences, all of which elicited unique rank orders for the shoes although each identified C1 as the "best" shoe condition. The results of the study support the necessity for within-subject analyses conducted with an adequate number of trials when attempting to detect subtle performance differences that may exist between various sport shoes. Whether the observed statistically significant differences are biomechanically meaningful remains an important unanswered question. PMID- 1943628 TI - Body configuration and joint moment analysis during standing long jump in 6-yr old children and adult males. AB - The purpose of the present study was to compare the body configurations and the joint function during standing long jump in 6-yr-old children and adult males. Twelve healthy adult males and eight (one male and seven females) 6-yr-old kindergartners participated in this study. Subjects performed standing long jump on a force platform with full effort. Body segment and joint angles were analyzed by high speed videography (100 frames.s-1). Using kinetic and kinematic data, joint moments, power, and work done were calculated through a free body diagram. Average standing long jump performances were +1.5 SD above Japanese norm in both adults and children. A wide range of motion of the lower limb segments during flight phase was found in the adults. In the crouch prior to take off, joint muscle power peaks appeared in the same order, and joint contribution to the total work done showed almost the same values in both adults and children. It is suggested that gross motor pattern before take off is almost accomplished by the 6-yr-old. Judging by hip joint work, adult performance was much better than that of children, since the adults exerted relatively higher negative work from the onset of preparatory movement to the point of lowest center of gravity during crouch. It was concluded that skilled 6-yr-old children have not fully developed either hip negative work during preparatory movement or body configuration in the flight phase, although gross motor pattern before take off phase was accomplished to skilled adult level. PMID- 1943629 TI - Training intensity of elite male distance runners. AB - To quantify training intensity in 13 nationally ranked male distance runners, training heart rates, environmental factors, and motivational factors were recorded throughout a 6-8 wk period of normal training. Variation in motivational and environmental factors such as intended effort, terrain, and running with companions altered training session mean heart rates by up to 4.min-1 (standard deviation). Heart rates and blood lactate concentrations, recorded in a series of steady-state treadmill runs, were used to convert training session mean heart rates to mean training speeds (TS) and to derive a measure of the anaerobic threshold (AT, the treadmill speed at a blood lactate concentration of 4 mmol.l 1). TS (15.6 +/- 1.4 km.h-1, mean +/- SD) was considerably lower than AT (20.2 +/ 1.1 km.h-1) in all subjects (P less than 0.001). Relative TS (TS expressed as a fraction of AT) differed significantly (P less than 0.001) between subjects and correlated significantly with the distance of the event for which the subject was training (r = 0.59, P less than 0.05). Relative TS may therefore be determined by the subject's or coach's perception of the appropriate intensity for the event. If the AT is the optimum training intensity, these subjects have considerable scope for improvement. PMID- 1943630 TI - Maximal anaerobic performance of the knee extensor muscles during growth. AB - The extent of the growth changes in maximal work output during 10 s (MWO10), 30 s (MWO30), and 90 s (MWO90) of maximal repetitive knee flexions and extensions assessed on a modified Hydra-Gym machine was investigated in 84 boys and 83 girls, 9-19 yr of age. Body weight, fat mass and fat free mass by underwater weighing, and thigh volume and cross-sectional area were also determined. No difference was observed in the absolute MWO10, MWO30, and MWO90 between girls and boys at 9 and 11 yr of age. However, significant differences appeared between genders from 13 yr of age onward, anaerobic performances of the knee extensor muscles of girls representing about 75% or even less of those of boys. The analysis of variance revealed that maximal work ouput during the three knee extension tests was significantly greater in males as well as in females from 9 to 18 yr, regardless how performance was related to morphological characteristics. Performance in absolute values or expressed per unit of body weight, fat free mass, and thigh cross-sectional area for the MWO10, MWO30, and MWO90 tests were almost always significantly lower in both genders when performances of the 9-yr-old group were compared with those of the 13-yr-old group or older groups. Improvement in maximal work output during the 10-s, 30-s, or 90-s knee extension tests with age occurred mainly between 9 and 15 yr in both genders. The results of the present study show that there are gender differences in predominantly anaerobic performances during growth and reveal that increase in muscle mass does not appear to be the only factor responsible for the age-related increment in the anaerobic working capacity of the knee extensor muscles. PMID- 1943631 TI - Indices of sustained aerobic power in young middle distance runners. AB - Sixteen young endurance athletes underwent physiological testing to determine their maximal oxygen uptake (VO2max), lactate threshold (lacAT), ventilatory threshold, and the slope variation point (SVP) of the linear relationship between running speed (RS) and heart rate (HR) both on the treadmill and during a field test, and the onset of blood lactate accumulation point. The RS, HR, VO2, and blood lactate concentration at which the different thresholds occurred were highly correlated, with r ranging from 0.82 to 0.90. The highest correlation was shown by RS at lacAT and RS at SVP during the field test. Various indices of sustained aerobic power in athletic children examined were shown to occur at a percentage of their VO2max similar to adult endurance runners. The tests developed for older athletes can be used in this age group as well. PMID- 1943632 TI - Protocol dependency of VO2max during arm cycle ergometry in males with quadriplegia. AB - The purpose of this study was to determine whether maximal oxygen uptake (VO2max) is protocol dependent during arm cycle ergometry (ACE) for quadriplegic males with spinal cord injuries (SCI). Twenty-four non-ambulatory subjects (aged 20-38 yr) with cervical SCI were divided into two groups based on wheelchair sports classification (IA group = 14; IB/IC group = 10). They underwent three different, continuous graded exercise tests spaced at least 1 wk apart on an electronically braked arm cycle ergometer. Following a 3-min, unloaded warm-up at 60 rpm, the work rate was increased 2, 4, or 6 W.min-1 for the IA group and 4, 6, or 8 W.min 1 for the IB/IC group. Ventilation and gas exchange were measured breath-by breath with a SensorMedics 4400 computerized system. Repeated-measures ANOVA showed no significant difference among the three protocols for VO2max in the IA group (P greater than 0.05). The mean (+/- SD) VO2max values (ml.kg-1.min-1) were 10.8 (+/- 3.4), 11.0 (+/- 2.7), and 10.2 (+/- 2.9) for the 2, 4, and 6 W.min-1 protocols, respectively. In contrast, the IB/IC group showed a significant difference among the protocols for VO2max (P less than 0.05). The mean (+/- SD) VO2max values (ml.kg-1.min-1) were 16.8 (+/- 4.5), 15.3 (+/- 4.3), and 14.6 (+/- 4.3) for 4, 6, and 8 W.min-1, respectively. Post hoc analysis revealed a difference between the 4 and 8 W.min-1 protocols. Our results suggest that graded exercise testing of SCI persons with quadriplegia, using ACE, should employ work rate increments between 2-6 W.min-1 and that work rate increments of 8 W.min-1 or greater will underestimate VO2max. PMID- 1943633 TI - Midwest wrestling study: prediction of minimal weight for high school wrestlers. AB - This study determined the validity of previously published or newly derived equations to predict fat-free body mass (FFB) in high school wrestlers from the midwestern United States. Five laboratories participated in the data-pooling study (total sample of 860 subjects). Measures included body composition by underwater weighing and anthropometric measurements of body mass, stature, and selected circumferences, diameters, and skinfolds. Cross-validation of selected equations to predict FFB revealed the lowest levels of error from the equations of Lohman, Thorland et al., Katch and McArdle, and Behnke and Wilmore. Modification of the constants in these equations or generation of new equations did not substantially reduce prediction error. Overall, total error for these top equations ranged from 2.44 to 2.59 kg. However, based on observed trends, this error was of lower magnitude with the younger and lighter subjects and of higher magnitude with the older and heavier subjects. We conclude that these equations could be used singularly or collectively to determine FFB, and a minimal weight could then be derived and assigned to a scholastic wrestler. PMID- 1943634 TI - The effect of progressive exercise on the equilibrium rebreathing cardiac output method. AB - The equilibrium CO2 rebreathing method has been used in the study of exercise cardiac output (Q) in health and disease, but the requirement for a steady state has usually limited its application to step function exercise. This limits testing to only a few levels of exertion in a laboratory session. We have devised a treadmill test where the grade is flat at the beginning and rises continuously at 1%.min-1 after stable measurements are obtained during level walking. The walking speed is determined by the subject's comfort and tolerance for fast walking. In series I seven normal subjects were studied with this protocol, and an automated system was employed for estimation of Q and oxygen uptake (VO2). For comparison of steady state and progressive tests, an interpolation method was devised which furnished a value of Q (progressive) that could exist at the value of VO2 obtained during the steady state. The average difference in Q so estimated between the steady state and the unsteady state was 0.3 l.min-1, SD = 1.7. This difference was less than the difference between averages of duplicate values of Q obtained during the steady state (1.11.min-1, SD = 16), and the difference between the two differences was not significant. Based on 51 determinations of Q and VO2 in eight normal subjects the unsteady state procedure furnished an average value of the relation slope of delta Q/delta VO2(-1) of 4.8 l.l-1. We conclude that the equilibrium CO2 method can be used to depict the Q, VO2 relationship over the range of VO2 at which rebreathing is tolerable. PMID- 1943635 TI - Case report: 30-yr-old female with exercise induced anaphylaxis. AB - This case describes a 30-yr-old white female who presented with a 2-wk history of pruritic rash with exercise. This rash occurred with each bout of exercise and was accompanied by one episode of light-headedness. A bicycle ergometer exercise challenge resulted in a fine wheal and flare rash of the trunk and upper extremities that was associated with symptomatic hypotension. She was diagnosed with exercise induced anaphylaxis, and initial treatment with hydroxyzine was instituted. Side effects from the drug were poorly tolerated, and she was switched to inhaled cromolyn sodium. She had noted resolution of her symptoms while she took cromolyn as recommended. Two months after her initial presentation, she also began to experience the same rash with hot showers. Exercise induced anaphylaxis is a well-described form of physical allergy that may be underdiagnosed. As the fitness boom continues and clinicians see more exercising patients, it will be important to recognize and understand this condition. It is a true anaphylactic reaction and, as such, certainly has the potential for significant morbidity and mortality. PMID- 1943636 TI - Reproductive dysfunction in amenorrheic athletes and anorexic patients: a review. AB - Strenuous athletic training and anorexia are associated with a high incidence of amenorrhea. While the physiological and/or psychological stressors that contribute to the development of menstrual dysfunction in these individuals appear to differ, they both involve disorders of the reproductive system that originate in the hypothalamus. The available data suggest that both groups experience alterations in the pulsatile release of GnRH, which in turn produces perturbations in pituitary and ovarian function ultimately leading to menstrual dysfunction. In this review, the reproductive and "stress" hormone profiles in amenorrheic athletes and anorexic patients are compared, and the interaction of these hormonal axes in the occurrence of menstrual dysfunction is discussed. PMID- 1943637 TI - [Does human distomiasis due to Fasiola gigantica exist in the delta of the Niger river in Mali? (apropos of a serological survey)]. AB - Finding of specific anti-Fasciola antibodies in persons living in the central area of the delta of Niger shows that human fascioliasis is a reality in Mali. Fasciola gigantica, the single species affecting livestock is probably the parasite concerned. We think that this parasitic disease in humans is underestimated, obscured by schistosomiasis which is hyperendemic in the country. Complementary studies are much needed for better identification of the problem. PMID- 1943638 TI - [Primary non-Hodgkin malignant lymphoma of the spleen in Africa. Apropos of 2 probable cases]. AB - The authors report two cases of primary splenic presentation of malignant lymphoma in Gabon. This disease seems very uncommon but its frequency is perhaps underestimated in Africa. The hypothesis of a possible relation with tropical splenomegaly deserves consideration. At the beginning of the disease large cell types follow a local growing pattern but symptoms are already obvious. Therefore early diagnosis would permit curative splenectomy. PMID- 1943639 TI - [Misleading forms of visceral leishmaniasis in children. Apropos of 5 cases]. AB - The authors report the cases of five children in whom kala-azar was undiagnosed at first instance. In these cases, the diagnosis was misled because of incomplete features (lack of fever, splenomegaly or hypergammaglobulinemia) an associated disease (hydatic cyst of the liver) or a complication dominating the clinical pattern (septicemia, staphylococcus respiratory infection). In one case, the patient was explored in order to diagnose portal hypertension. PMID- 1943640 TI - [The big vipers of Africa of the genus Bitis Gray, 1842 and their venom. Zoological, biochemical and clinical data]. AB - After the suggestion of the genus Bitis Gray, 1842 snakes, we studied in details three species, among the largest and most widespread ones: Bitis arietans, Bitis gabonica and Bitis nasicornis. The main morphological characteristics and some of the zoological data presented may be very useful, as well as the clinical signs, for physicians to identify, the snake that bits a patient. Thus, an adapted treatment can be undertaken. The biochemical composition of the venoms and their experimental toxicity are also presented for a better understanding of the clinical symptoms. PMID- 1943641 TI - [Eye injuries in the Cameroon environment of Yaounde]. AB - From 1st January 1988 to 31st September 1990 1.321 cases of eye injury were seen in our service. These cases represented 12.24% of our consultations: 911 males and 410 females. The average age was 27 years and there were two peaks of 0-9 years and 20-29. About half of those injured were students with fights constituting the principal cause of injuries. The left eye was more often affected than the right. The complications encountered were many and varied. PMID- 1943642 TI - [Tuberculous allergy in a population of 3-to-23-month-old children in Bangui (Central African Republic)]. AB - In 1986, vaccinal allergy has been looked for by tuberculin RT 23 intradermal reaction within a random group of 354 Central African Children aged of 3 to 23 months and immunized in the Mother and Child Care Services in Bangui in the framework of the Enlarged Vaccination Program, with the same B.C.G. strain during their postnatal period. Percentage of intradermal reactions equivalent or superior to 6 mm get down with time, of progressive but fast mode from 56.2 p.c. in the age group of 3 to 5 months to 20.2 p.c. in the ones of 12 to 23 months. Nevertheless, the authors recommend B.C.G. immunization in urban milieu during the postnatal period because of the strong vaccinal protection one get, but recommend also a systematic booster injection during the second year of childhood. PMID- 1943643 TI - [Sampling survey on the frequency of digestive diseases in Algeria]. AB - In order to assess the frequency of digestive diseases like peptic ulcer and gallstone in Algiers, a sampling survey was carried out among 1,515 households, ie 10,486 inhabitants. The diagnosis of these diseases was collected by questioning but it had to be established previously in a health structure. The design of the survey gets both from the backward prevalence study to assess annual prevalence and the prospective study in the past to assess quarterly incidence. Males had almost twice the risk of having an ulcer than females. Females had a risk nearly four times higher to have a gallstone than males. The highest prevalence rate for ulcer (92.3 per 1,000) was observed among males between 55 and 64, while the highest incidence rate was noted among young men between 25 and 34 (5.7 per 1,000). Hospitalization rate for ulcer was 2.8 per 1,000 inhabitants. Females aged between 65 and 74 years had the highest prevalence rate for gallstone (44.8 per 1,000). Females had an increasing risk with increasing age to have a gallstone. Because they are exempt from certain disadvantages of hospital studies, the household surveys can improve the epidemiological understanding of digestive diseases. PMID- 1943644 TI - [Health care accessibility and adequacy of health care system in the Sanaga basin (Central Cameroon)]. AB - The authors report on the results of a Survey Carried out in four areas in Center Cameroon. Health gets a major position within the concerns of the population to protect it, they prefer the classical and official system of health Care rather than the primary Health care System. Self-medication is also a preferred solution. In the rural milieu, they often pay a visit to a traditional practitioner. When they have to take a decision, geographical situation and money problem play both a major role. PMID- 1943645 TI - [Risk factors for malnutrition in 0-59-month-old infants in 2 districts of Niger]. AB - A nutritional survey by cluster sampling at 2 degrees, carried out in April 1987 within a range of action of 6 health structures in Niger, has permitted the calculation of the weight/height index among children aged from 0 to 59 months and the malnutrition rate, according to the socio-economic status, the demographic variables, the intercurrent diseases, the use of health departments, alimentary and weaning habits. The standardized rate of acute malnutrition for the age among of 0-59 months is 12.3%. The risk factors for acute malnutrition retained after logistical regression are the age groups of 6-17 months and 18-29 months, the areas of Guidan Roumdji, Tahoua, Tajae, Guidan Sori and the group of children that have contracted diarrhea during the 15 days preceding the survey. PMID- 1943646 TI - [The value of radiological screening in the Tunisian army]. AB - In a non orientated study of 12,357 radio-detecting of the new recruits the authors noticed that tuberculosis is still occupying a privileged place despite the effort made for prevention, and a retreat of post-infectious bronchiectasis of childhood. The authors underline the necessity to continue systematic detecting despite the low percentage of restrained anomalies, this is for two reasons: *on the one hand to avoid the little tuberculosis epidemic of the barracks *on the other hand for an early treatment of the other affections especially heart affections. PMID- 1943647 TI - [From suspicion to diagnosis. Clinical, epidemiological, radiological and endoscopic aspects of bronchopulmonary cancer in Senegal. Apropos of 700 endoscopies performed at the Principle Hospital of Dakar from 1987 to 1990]. AB - 700 bronchial endoscopies were performed over a period of three years at the Dakar "Hopital Principal". 40 bronchopulmonary cancers were identified (34 epidermoid, 4 adenocarcinoma, 2 with "small cells") out of 80 suspect cases. When we examine the clinical, radiological, endoscopic features, we are able to classify the following as the most established facts: 1. Higher radiological frequency of the pulmonary retractile condensation syndrome (40 cases). 2. Main frequency of proximal granulated tumors (45) in comparison with endoscopic bronchial stenosis (22). 3. Identification almost exclusive of bronchial epidermoid cancer in that series (34). 4. Male sex and smoking are two unequivocal elements of that pathology. Bronchial endoscopy, absolutely necessary test easy to perform and to get, enables to visualize a lesion and to bring forward the indisputable histological evidence through the biopsy either alone or associated with endoscopic brushing and alveolar washing. PMID- 1943648 TI - [A new case report of traumatic rupture of the diaphragm (University Hospital Center Kamenge-Bujumbura)]. AB - Classified as a part of thoraco-abdominal traumas and polytraumas, midriff traumatic rhexis must be operated as soon as possible. A new case of the rhexis of a left dome confirms this notion admitted by all. Their peculiar prognosis is generally very good but all depends on the possible associated lesions able to hamper the vital prognosis. PMID- 1943649 TI - [What course to take in donovanosis? Apropos of a new case report (Hospital Center of Libreville- Gabon)]. PMID- 1943650 TI - [Non-obstructive necrotizing acute enterocolitis (apropos of a case report) )University Hospital Center Kamenge-Bujumbura)]. AB - The authors report on a new case of acute necrotic non obstructive enterocolitis. Discussion is mainly centered on the nosological framework of this uncommon affection, occurring in an infectious background, and on its etiopathogenetic mechanism. Several hypothesis are formulated. Because of the seriousness of its prognosis, it is emphasized on the necessity of a rapid surgical intervention. PMID- 1943651 TI - Dextran magnetite as a liver contrast agent. AB - The superparamagnetic particle dextran magnetite was studied as a liver tumor contrast agent for magnetic resonance imaging (MRI). The effects of dextran magnetite on the longitudinal (T1) and transverse (T2) relaxation times in liver, spleen, and an implanted rat liver tumor were measured at 0.47 T (IBM/Bruker PC 20 relaxometer) over the dose range of 23 to 69 mumol Fe/kg. Dextran magnetite substantially reduced the T2 of the liver and spleen, but not of the tumor, thereby providing a basis for improved tumor imaging. The T1 of the tumor was not affected following injection of dextran magnetite in the dose range studied, while the spleen T1 was reduced substantially more than the T1 of the liver. Histological studies using the iron reaction for Prussian blue clearly showed dextran magnetite in the liver and spleen, but not in the tumor. While dextran magnetite was sequestered in macrophages in both liver and spleen, the distribution in the liver was more diffuse (70 microns average particle separation) than that in the spleen (25 microns separation). The lack of a T1 effect in the liver is consistent with the fact that a majority of the water in the tissue cannot diffuse to the relaxational centers on the time scale of the liver's intrinsic T1 (280 ms). In the spleen, however, the dextran magnetite is more densely packed in the red pulp allowing a significant fraction of the water to be relaxed by a T1 mechanism. Spin-echo images of the implanted tumor (mammary adenocarcinoma. R3230AC) in the livers of Fischer 344 rats were obtained at 0.50 T (Siemens Magnetom). The tumor-to-liver contrast was improved for both T1 and T2 weighted spin-echo images after intravenous injection of the dextran magnetite contrast agent. The contrast determined from these images agreed with that predicted by the measured T1 and the T2 (Hahn spin-echo) values. In addition, gradient-echo T2-weighted images with good contrast were obtained in a much shorter imaging time than was needed for T2-weighted spin-echo images. These results demonstrate that the MRI contrast enhancement observed with dextran magnetite is based on its selective uptake and distribution in the macrophages in the liver and spleen and that this agent has substantial potential as a superparamagnetic MR contrast agent. PMID- 1943652 TI - The effects of chronic ethanol consumption on the intact rat liver studied by in vivo 31P NMR spectroscopy. AB - In vivo 31P nuclear magnetic resonance (NMR) spectroscopy provides unique opportunities to study the biochemistry of an organ within the intact animal in a totally non-invasive way. We have used in vivo and in vitro 31P NMR spectroscopy to study steady state changes in the major phosphorus-containing metabolites of the rat liver in control and chronically ethanol-treated rats. Chronic (4 month) ethanol treatment caused a statistically significant increase in the inorganic phosphate and phosphodiester resonances of rat liver in in vivo 31P NMR spectra relative to pair-fed control rats. Phosphomonoester and adenosine 5'-triphosphate resonances, as well as intracellular pH, were not appreciably altered. The effects of chronic ethanol treatment were particularly apparent in the response of the liver to a metabolic challenge of glycerol. Glycerol is phosphorylated almost exclusively in the liver and metabolized predominately via glycolysis and gluconeogenesis. Our in vivo 31P NMR results after administration of glycerol showed a significant increase in the phosphomonoester resonance in the liver of chronic ethanol-treated rats but not for their pair-fed controls. In vitro 31P NMR studies of perchloric acid extracts of liver showed that the increase was due to an accumulation of sn-glycerol 3-phosphate. This effect is due to the NAD(+) dependent glycerol 3-phosphate dehydrogenase step being inhibited in the chronic ethanol-treated rats. This glycerol test may be useful in assessing the ability of the liver to rapidly regenerate NAD+ in situ and may be a more sensitive indicator of redox imbalance than steady state ratios of redox pairs (e.g., lactate/pyruvate). PMID- 1943653 TI - Rapid, fully automatic, arbitrary-volume in vivo shimming. AB - MR spectroscopy and many MR imaging methods benefit from a well-shimmed magnet. We have developed a pulse sequence which enables fast and accurate measurement of three-dimensional field maps in vivo, and a data analysis package that allows calculation of shim currents to optimally shim arbitrary selected volumes. A data link to the shim power supply allows automatic update of currents. No intervention by the operator is required. Typical in vivo shimming time is less than 5 min. Performance analysis, phantom, and in vivo results are presented. PMID- 1943654 TI - NMR angiography of coronary vessels with 2-D planar image scanning. AB - On the basis of the principles of the time-of-flight method and the 3-D angiogram obtained by the 2-D planar image scanning technique using 90 degrees RF pulses with short repetition time, we have obtained a coronary angiogram around the heart including the coronary arteries and veins. The cine NMR imaging technique is also incorporated in synchronizing ECG R waves to reduce the motion artifact and at the same time to induce the saturation effect on the static samples. Images of the large bulk blood flow corresponding to the heart chamber and descending aorta are further removed by postprocessing. The final 3-D angiogram is then formed by stacking the 2-D images and contrast is further enhanced by the maximum ray tracing algorithm. PMID- 1943655 TI - 19F NMR imaging of cerebral blood flow. AB - Techniques for the quantitative imaging assessment of cerebral blood flow are presented in a cat using 19F NMR imaging of trifluoromethane. The input function of the indicator was acquired noninvasively, while its uptake and clearance were followed in 2-cc volume voxels from images acquired at 67 s intervals. A single compartment model yielded normal cerebral blood flow estimates. PMID- 1943656 TI - Diffusion-weighted imaging of kainic acid lesions in the rat brain. AB - We present T2-weighted and diffusion-weighted images of kainic acid lesions in the rat brain. Our observations show improved image contrast between edematous lesions and unaffected tissue using diffusion-weighted imaging. Furthermore, we show that the anisotropic intensity changes associated with this sequence can be used to highlight white matter tracts and to provide information concerning their orientation in the rat brain. PMID- 1943657 TI - Delayed-focus pulses for magnetic resonance imaging: an evolutionary approach. AB - An evolutionary algorithm has been used to design a family of shaped radiofrequency pulses giving uniform absorption-mode excitation across a predetermined frequency band. By allowing a free precession interval before signal acquisition, time is left for field gradients to be switched and for undesirable transients to decay. PMID- 1943658 TI - In vivo 13CNMR spectroscopy of glucose metabolism of RIF-1 tumors. AB - An efficient method for measuring in vivo 13C NMR spectra of tumors has been developed and employed to monitor glucose metabolism in radiation-induced fibrosarcomas (RIF-1) subcutaneously implanted in C3H/HeN mice. [1-13C]Glucose was injected directly into the tumors at a dose of 1 g/kg body wt. Spectra were obtained with a Bruker AM 360-WB spectrometer (8.4 T/8.9 cm bore) employing a homebuilt probe equipped with a four-turn solenoidal coil (1.5 cm outer diameter) for detection of 13C signals and a Helmholtz coil (two 3-cm turns separated by a 3-cm gap, oriented orthogonally to the 13C coil) for 1H decoupling. In addition to the natural abundance 13C resonances of the tumors, signals were detected from the alpha- and beta-anomers of labeled glucose. Within 15 min following injection of labeled glucose [3-13C]lactate and [3-13C]alanine were detected. Lactate labeling approached steady state levels within about 50 min after glucose injection: in contrast, alanine labeling increased continuously over the duration of the experiment (70 min). Sixty minutes after glucose injection, the ratio of the intensity of [3-13C]lactate to the principal lipid methylene resonance (30 ppm from external tetramethylsilane), which served as an internal intensity reference, was correlated with tumor size, whereas the corresponding ratio of the [3-13C]alanine resonance was not. Labeling of glutamate was below the level of detection in the in vivo spectra; however, labeling of C4-glutamate at a level approximately 50-fold lower than the level of [3-13C]lactate was detected in perchloric acid extracts. Incorporation of 13C label into C2- and C3-glutamate and C2-lactate was also observed. PMID- 1943659 TI - Double-volume 1H spectroscopy with interleaved acquisitions using tilted gradients. AB - A method is presented by which volume selective in vivo 1H spectra of two different voxels can be acquired in an interlaced mode using PRESS or STEAM spectroscopy. Spatially tilted gradients are employed for voxel definition so as to avoid mutual saturation. Independent volume selective shimming of the voxels is possible. Two spectra of volumes as small as (1.5 cm)3 can be acquired from human brain within 14 min even from very disadvantageous locations close to air borne interfaces. PMID- 1943660 TI - Noise correlation. AB - Calculations and experiments that provide support for our previously stated theorem are presented: If two coils simultaneously receiving magnetic resonance signals from the same anatomic region exhibit zero mutual inductance, there can be no correlation of the noise. It is shown that correlation does not exist even in the presence of mutual inductance unless the two signal paths have amplifiers prior to signal combination. It is further found that in the presence of mutual inductance with ideal amplifiers (0 dB noise figure) in the two signal paths, there is no correlation of noise. In order to satisfy the condition of zero mutual inductance, it may be necessary to employ a decoupling circuit external to the body. A novel coil assembly, which was used in the experiments, places a single-turn surface coil in the median plane between the two loops of a counter rotating current coil. The signal-to-noise ratio can be improved by combining signals. This is in analogy to quadrature receiving coils, where the mutual inductance is zero because vector reception fields are perpendicular. In the present geometry, vector reception fields are collinear, but are parallel and antiparallel on the two sides of the coil assembly, resulting in zero mutual inductance. PMID- 1943661 TI - Quantitation of metabolites by 1H NMR. AB - In this report we describe the three factors that need to be measured when quantitating an edited resonance relative to an internal standard using a surface coil. These factors are necessary by virtue of the water, fat suppressing, and localization schemes used in studing a 1H metabolite. First, use of semi selective pulses requires amplitude correction of the edited and reference resonances. Second, use of a single surface coil results in different sensitive volumes for different resonances due to the inhomogeneous B1 and therefore require separate acquisition of the resonances. Third, editing pulses alter the sensitive volumes and this correction must be made internally by applying the same editing pulse to the reference resonance. A rationalization of this correction is given in terms of rotation operators. We apply these corrections to quantitate edited lactate relative to total creatine in a MnCl2-doped phantom and find 91% rather than 145% of known concentration. In human skeletal muscle in vivo after exhaustive exercise, we measured the lactate after exercise and found it to be 27.2 mM in two experiments, in reasonable agreement with literature values for the given exercise protocol. PMID- 1943662 TI - Correlation of lactate and pH in human skeletal muscle after exercise by 1H NMR. AB - We have made in vivo 1H NMR measurements of the time course of pH and lactate in human skeletal muscle after exercise. Spectra were obtained in a 4.7-T 30-cm bore Bruker Biospec spectrometer with a 2.5-cm diameter single surface coil. pH was determined from the shift of the endogenous carnosine H-C2 peak while lactate concentrations were determined by comparison with endogenous total creatine, taken to be 28.5 mM/kg wet wt. Fitting the data shows that the exponential decay of lactate (-0.094 +/- 0.014 min-1. t1/2 = 10.6 min) is slower than that of pH ( 0.147 +/- 0.015 min-1, t1/2 = 4.7 min), n = 7 with two different volunteers. These values are significantly different with P less than 0.0005. Relaxation times of lactate and creatine were also measured for lactate quantitation; creatine T1, 1.23 +/- 12 s, T2, 136.2 +/- 26.4 ms (both in resting human muscle); lactate T1 (in postmortem rabbit muscle), 1.0 +/- 11 s and T2, 80 ms (in postexercise human muscle). At the end of intense exercise, the lactate level reached was 25.3 +/- 4.0 mM and the average pH drop was 1.0 pH unit. We discuss the implications of these measurements in conjunction with existing data on other sources of H+ flux, phosphocreatine resynthesis, H+ transport, and contribution of inorganic phosphate to buffering. PMID- 1943663 TI - Application of missing pulse steady state free precession to the study of renal microcirculation. AB - Missing pulse steady state free precession (MP-SSFP), an extension of steady state free precession (SSFP), was evaluated for its ability to measure slow fluid flows. In experiments using flow phantoms, the MP-SSFP signal was sensitive to fluid velocities in the millimeters per second range. Isolated perfused rabbit kidneys were then used to determine if MP-SSFP could measure perfusion in a biological tissue. The signal intensities in the different anatomical regions of the kidney were observed to be related to the total flow to the organ. Furthermore, increasing the flow sensitivity of the pulse sequence by increasing the gradient strength resulted in decreases in the image signal intensity. The MP SSFP signal was more sensitive to flow in the medulla than in the cortex. This can be related to slow flow sensitivity of MP-SSFP and the known differences in velocity profiles between these two regions. These results suggest that MP-SSFP may be a powerful tool for the noninvasive measurement of slow fluid flows in different regions of the kidney. PMID- 1943664 TI - Regional 1H transverse magnetization studies in perfused rabbit kidney. AB - A Carr-Purcell-Meiboom-Gill imaging sequence consisting of 128 echoes is used to extract transverse magnetization decay curves (TDCs) at 1.9 T from 1.7 x 1.7 x 5 mm3 voxels within the cortex, outer medulla, and inner medulla of perfused rabbit kidneys. The spatially localized TDCs within each tissue type are found to be better approximated by biexponential, as opposed to monoexponential, functions. The biexponential parameters characterizing the TDCs demonstrate an improved degree of tissue specificity over that available from monoexponential analyses. The fraction of the quickly relaxing TDC component and the relaxation rate of this component are observed to decrease from cortex to inner medulla. A two-site exchange analysis is used to convert biexponential TDC parameters into water volume fractions and exchange rates. The exchange rates between the fast and slowly relaxing pools increased from cortex to inner medulla. All exchange rates were less than 1.5 Hz, indicating a relatively slow water exchange process. The imaging methods and subsequent analyses offer the potential to generate unconventional MR images with tissue contrast dependent upon water compartmentation and exchange. PMID- 1943665 TI - Pre- and postmortem diffusion coefficients in rat neural and muscle tissues. AB - Pulsed gradient diffusion-weighted spin-echo images (7 to 11 gradient strengths) were obtained in a coronal slice through the midbrain for five normal adult white rats before and after sacrifice in a 2-T CSI system with air temperature control. The pulse sequence was cardiac gated and respiratory synchronized in order to minimize motion artifacts (Tr greater than 2 s. Te = 30 ms). Diffusion coefficients reflecting several tissue compartments (D*) in brain and muscle were calculated and referenced to simultaneously imaged tubes of water. In the living animals, brain cortical matter had a value of D* = (0.82 +/- 0.02) x 10(-3) mm2/s. deeper brain regions had a value of D* = (0.73 +/- 0.02) x 10(-3) mm2/s, and the muscle had a value of D* = (1.4 +/- 0.1) x 10(-3) mm2/s. Postmortem the values in brain dropped by approximately 30%, while remaining constant in muscle. Signal intensity in the spin-echo images for muscle tissue rose by 50% over a 1- to 2-h interval after sacrifice while that of brain tissue remained relatively stable. PMID- 1943666 TI - Proton spectroscopic imaging: a tool for studying intracerebral tumor models in rat. AB - Water-suppressed 2D 1H spectroscopic imaging was used with surface coils to study in vivo the cerebral metabolism changes in rat brain induced by a glial tumor growing in situ. To achieve slice selection without a chemical-shift artifact, we exploited the depth pulse properties of a spin-echo sequence. In order to give a spectral response which is independent of the position, the water suppression was achieved by using a spin-locking excitation and a binomial refocusing pulse. Spectroscopic images were obtained with an in-plane resolution of 1.1 X 1.1 mm and a slice thickness of roughly 3 mm. The growing of the tumor induced dramatic modifications in the proton spectra, including a nearly complete loss of N-acetyl aspartate, an increase of the 1.3-ppm peak, an increase in choline, and a decrease in creatine. The results demonstrate the potential of spectroscopic imaging in the study of intracranial tumor models in rats. PMID- 1943668 TI - The magnetic field dependence of proton spin relaxation in tissues. AB - The magnetic field dependence of water-proton relaxation is reported for a simple protein solution, a cross-linked protein solution, and a series of rat tissues, fresh, dried and rehydrated. The shape of the magnetic field dependence associated with water proton relaxation in tissues is accounted for by magnetic dipole-dipole interactions between the mobile water spins and the immobile spin populations of the nonrotating components of the tissue coupling the behavior of the immobilized spin system to that of the mobile water spin system. The effect of this coupling is to impart the field dependence of the relaxation associated with the immobilized spin population to that of the mobile water spins that are observed in most relaxation and imaging experiments. PMID- 1943667 TI - Analysis of phospholipids in human amniotic fluid by 31P NMR. AB - A recently described solvent-reagent system for obtaining narrow linewidths in 31P NMR spectra of phospholipid extracts was applied to human amniotic fluid. Resolution of the major components was achieved by manipulating the solvent composition, and assignments were made by spiking samples with standard compounds. Spin-lattice relaxation times were determined and used to optimize data acquisition. NMR estimates of the phosphatidylcholine to sphingomyelin ratio for 33 patients were compared to those obtained by TLC densitometry, a common clinical assay for fetal pulmonary maturity. Estimates of the levels of phosphatidylglycerol and phosphatidylinositol could also be obtained from 31P NMR. High-resolution 31P NMR in this solvent-reagent system provides a relatively straightforward and reliable alternative method for assessing fetal pulmonary status by phospholipid quantitation in human amniotic fluid. The 31P NMR method has the advantage that it is sensitive to total, and not just unsaturated, phosphatidylcholine. PMID- 1943669 TI - A means of microsphere reference sampling that is compatible with nuclear magnetic resonance instruments. PMID- 1943670 TI - Real-time magnetic resonance imaging of laser heat deposition in tissue. AB - We applied diffusion-sensitive echo planar (Instascan) imaging to study thermal changes caused by a Nd:YAG laser. Images of phantom materials and normal rabbit brain tissue in vivo, acquired in 150 ms, every 2s, clearly showed the dynamics of temperature-related signal intensity changes in the regions irradiated by the laser. PMID- 1943671 TI - A simple method for obtaining cross-term-free images for diffusion anisotropy studies in NMR microimaging. AB - The geometric average of two spin-echo images obtained with opposite polarity diffusion gradients yields cross-term-free images that can be directly compared for diffusion anisotropy. This approach is demonstrated here for free water isotropic diffusion and anisotropic diffusion of water in the phloem system of celery (Apium graveolens). PMID- 1943672 TI - High-resolution 1H NMR imaging of regional ischemia in the isolated perfused rabbit heart at 4.7 T. AB - High-resolution 1H NMR images of the isolated perfused rabbit heart were recorded before and after the induction of regional ischemia while the heart was arrested. On T2-weighted images the ischemic region appeared darker than the surrounding tissue and a 28% reduction in T2 was measured from the images. Infusion of an NMR contrast agent demonstrated that the hypointense region on the T2-weighted image was from the ischemic region, which was further confirmed by histological analysis of the heart. It is proposed that the decreased T2 in the ischemic region may be a consequence of changes in water compartmentalization. It is possible that these changes may be used to follow the evolution of tissue injury during ischemia, and therefore provide information regarding the transition between reversible to irreversible injury in the isolated perfused heart. PMID- 1943673 TI - Cardiac tagging in the rat using a DANTE sequence. AB - We demonstrate the application of a DANTE tagging sequence to in vivo imaging of the rat heart. This sequence generates narrow parallel tag lines in a short space of time and is combined with cardiac gating to image the heart wall at eight points throughout the cycle. PMID- 1943674 TI - CSF-suppressed quantitative single-shot diffusion imaging. PMID- 1943675 TI - A complete solution to the model describing Carr-Purcell and Carr-Purcell-Meiboom Gill experiments in a two-site exchange system. AB - A general solution for the relaxation decay function observed in both CP and CPMG spin-echo experiments, performed on systems governed by a two-site chemical exchange mechanism, is presented. This solution not only provides the relaxation time constants, but also supplies complete information about relative component sizes. Solutions are analytical, but results are complex enough to warrant computer-assisted calculations. Programming suggestions, based on the extensive tests performed, are provided. PMID- 1943676 TI - Correction for chemical-shift artifacts in 19F imaging of PFOB: simultaneous multislice imaging. AB - One of the difficulties encountered in 19F NMR imaging of fluorinated blood substitutes is that these compounds often exhibit complex multipeak spectra. These peaks result in chemical-shift artifacts along the readout direction and blurred images. In addition, each peak excites a different slice (mis-selection) when a slice selection gradient is applied during the selective rf pulse. A simultaneous multislice imaging method has been developed to solve the inherent problem of mis-selection. The essence of this method is to use the two strongest peaks of the spectrum to excite controlled different multiple slices simultaneously, with or without a slice gap. The images corresponding to the two spectral lines are then separated from in- and out-of-phase images (Dixon method). This method corrects the problem of mis-selection and either improves the SNR or increases the number of slices over spectrally selective methods which image only one peak. PMID- 1943677 TI - MRI of the pancreas transplant: lack of correlation between imaging and clinical status. AB - Twenty-five MRI scans were performed on 14 patients with cadaveric pancreatic transplants to determine the role of this modality in the evaluation of transplant dysfunction. Our population included 12 normal transplants and 13 recipients with pancreatic graft dysfunction (either rejection or pancreatitis). Six of the latter patients had two or more scans permitting reassessment of the same transplant in various states of health. T1-and T2-weighted MR images were evaluated qualitatively and quantitatively to see if certain patterns were associated with clinical status. We found that although MRI was capable of producing excellent images of the in situ pancreatic transplant, this modality was unable to reliably distinguish the normal from the abnormal transplant. This conclusion differs from prior assessments; possible reasons for this are discussed. PMID- 1943678 TI - Coil optimization for MRI by conjugate gradient descent. AB - A flexible iterative algorithm is presented for optimizing gradient and radio frequency coils for MRI. It is based on a model using discrete current elements and direct Biot-Savart calculation of the fields. An error function is defined over a region of interest (ROI) and is minimized by conjugate gradient descent. The choice of error function allows optimization of the field uniformity, the inductance, and the efficiency of the coil in any combination. Neither the coil nor the ROI is restricted to any particular geometry. A 40-turn cylindrical z gradient coil of radius a and length 4a, designed for ROI of radius 0.7a and length 2a has an average error in the gradient fields generated of 0.85%, an inductance of 0.014a mH/cm, and an efficiency of 6.65a-2 Gcm/A. A 16-turn birdcage-like RF coil of radius 5 cm, designed for a ROI of radius 4 cm has an average error of 0.79%. PMID- 1943679 TI - Elevation in relative levels of brain membrane unsaturated fatty acids in Alzheimer's disease: high resolution proton spectroscopic studies of membrane lipid extracts. AB - Unsaturation indices of cerebral cortex membrane phospholipids in Alzheimer's disease were determined utilizing high resolution proton nuclear magnetic resonance (NMR) spectroscopy of lipid extracts. The unsaturation index of Alzheimer's brain was found to be significantly higher (P less than 0.01) than that of age-matched controls. The study provides further support for the hypothesis that alteration in phospholipid metabolism, especially an elevation in unsaturated fatty acids, may play a role in the pathogenesis of Alzheimer's disease. PMID- 1943680 TI - SLIP, a lipid suppression technique to improve image contrast in inflow angiography. AB - In rapidly acquired gradient echo images, lipid regions usually appear as areas of high signal intensity. In 2D inflow angiograms processed by the maximum intensity projection algorithm, this high lipid signal may prevent angiographic visualization of some blood vessels. We present a new approach to suppress the lipid signal, SLIP, spatially separated lipid presaturation. The SLIP technique suppresses lipid signal over a narrow region by exploiting the chemical-shift effect. SLIP requires an arrangement of a thin slice and a wide presaturation slab already available in 2D inflow refreshment angiography. Thus SLIP was incorporated to an inflow angiography sequence without increasing the acquisition time. The use of SLIP resulted in considerable improvement in angiographic contrast and increased the number of vessels detected in projection angiograms. The SLIP technique does not require high homogeneity of the main magnet field. PMID- 1943681 TI - Magnetic resonance imaging study of the rat cerebral ventricular system utilizing intracerebrally administered contrast agents. AB - Magnetic resonance imaging (MRI) was employed to study the rat brain in conjunction with intracerebral (ic) injection of three contrast agents: GdHAM, GdDPTA, and MnCl2. The results demonstrate several advantages of ic administration of MRI contrast agents over the other routes of injection in examining CSF dynamics and brain ventricular structure. Apparent affinity of the luminal ventricular wall of the brain for positively charged GdHAM and Mn2+ ions is observed, presumably reflecting the presence of negatively charged wall components. Respiratory distress caused by (intravenous) injection of GdHAM was found to be minimized in the case of ic injections. Time-dependent changes in observed contrast indicate that diffusive processes rather than flow of CSF play a dominant role in distributing the contrast agents. Possible applications of this approach in brain research are discussed. PMID- 1943682 TI - Histidase and histidinemia. Clinical and molecular considerations. AB - Histidase (histidine ammonia-lyase, EC 4.3.1.3) catalyzes the deamination of L histidine to trans-urocanic acid in the liver and skin of mammals. Histidase deficiency results in increased histidine and histamine in blood, and decreased urocanic acid in blood and skin. In this review we discuss current research on: (1) the mechanism of formation of an unusual residue, dehydroalanine, at the active site of histidase; and (2) the role of urocanic acid as an ultraviolet light-induced immunoregulator in the skin, and the implications of urocanic acid deficiency for human histidinemia. Genetic mechanisms that may account for the 1% of histidinemic patients with neurological impairments are considered briefly. PMID- 1943683 TI - Molecular basis of prolidase (peptidase D) deficiency. AB - Human prolidase (PEPD, iminodipeptidase, EC 3.4.13.9) and related deficiencies were analyzed in terms of the nature and molecular biology of the enzyme and the molecular events seen in patients with this deficiency. The analyses were based on findings concerning isolation of the enzyme, development of specific antibodies and molecular cloning of cDNA and genome DNA of human prolidase. The studies revealed that human prolidase is a homo-dimer of an identical subunit 492 amino acid residues. The gene for prolidase (PEPD gene) was localized on chromosome 19, spanned more than 130 x 10(3) base-pairs and split into 15 exons. Molecular defects in prolidase deficiency were then analyzed. Two patients with the polypeptide-positive phenotype of the disease carried a mis-sense mutation of exon 12. Two siblings with a polypeptide-negative phenotype carried a gene deletion that encompassed exon 14. These mutations were not found in ten other patients with the disease, hence the molecular defects in prolidase deficiency are apparently highly heterogeneous. PMID- 1943684 TI - Effect of cholera toxin on L-[14C]glycine uptake and intestinal cell enzymes in rabbit. AB - The uptake of L-[14C]glycine and the activities of intracellular marker enzymes of enterocytes were studied in ligated small intestinal segments of rabbits during experimental cholera induced by intra-intestinal injection of pure cholera toxin (CT). No significant difference was observed in the active uptake of L [14C]glycine between the CT-injected small intestinal segments and the saline injected control segments, indicating that there is an intact active transport system for intestinal absorption of L-[14C]glycine during experimental cholera in rabbits. Apart from a significant increase in the activity of a brush border marker enzyme (alkaline phosphatase), there was no significant difference between the activities of marker enzymes for lysosomes (acid phosphate), microsomes (glucose-6-phosphatase), mitochondria (succinate dehydrogenase), and a cytosol enzyme (proteinase) in mucosal homogenates of CT-injected small intestinal segments compared to controls. The finding of an intact mitochondrial marker enzyme together with intact L-[14C]glycine absorption provides a scientific basis for considering the use of glycine and other monoamino monocarboxylic amino acids in "improved" oral rehydration solutions for the treatment of acute diarrhea, including cholera. PMID- 1943685 TI - Regulation and expression of type V (tartrate-resistant) acid phosphatase in human mononuclear phagocytes. AB - Human type V (tartrate-resistant) acid phosphatase belongs to a unique group of iron-binding proteins that includes uteroferrin and other purple phosphatases. The enzyme is normally restricted to osteoclasts and certain phagocytic cells but its role is unknown. We show that phosphatase mRNA is abundant in cells of monohistiocytic phenotype and that enzyme expression in cultured human monocyte derived macrophages is depressed by gamma-interferon and bacterial lipopolysaccharide, agents that promote functional differentiation in these cells. In contrast, phorbol ester, which stimulates intracellular calcium mediated events, greatly enhances type V phosphatase expression and mRNA abundance. Lymphokine and phorbol ester-modulated expression of type V acid phosphatase expression thus represents a model system for investigating proliferative responses that are specific to cells of the mononuclear macrophage system. PMID- 1943686 TI - Non-random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase-related) oculocutaneous albinism. AB - Type I oculocutaneous albinism (OCA) is produced by mutations of the tyrosinase gene. We report four new missense mutations in the tyrosinase gene in patients with type IA OCA. Three of these mutations occur within exon I and the fourth mutation within exon IV. Analysis of the distribution of these four missense mutations and 12 previously reported missense mutations shows that most cluster in four areas of the gene. Two clusters involve the copper A and copper B binding sites and could disrupt the metal ion-protein interaction necessary for enzyme function. The other two clusters are in exon I and exon IV and could represent important functional domains of the enzyme. We conclude that analysis of the tyrosinase missense mutations will provide insight into the structure-function relationship of this enzyme. PMID- 1943687 TI - Phenylketonuria and the phenylalanine hydroxylase gene. AB - The application of the tools of molecular biology has led to a profound increase in our current understanding of the nature of the disease states associated with defects in the phenylalanine hydroxylase (PAH) gene. Over the past decade, the PAH cDNA has been cloned and the primary structure of the PAH protein has been determined. The PAH cDNA clone has served as an invaluable probe to define the molecular structure and chromosomal location of the PAH locus in both man and other organisms. Southern analysis using the PAH cDNA as a hybridization probe has revealed the presence of numerous restriction fragment-length polymorphisms (RFLPs) in the PAH gene, which have permitted the classification of normal and mutant PAH chromosomes. RFLP analysis has also permitted the implementation of prenatal diagnosis of phenylketonuria (PKU) and other related hyperphenylalaninemic disorders. Through the use of molecular cloning and polymerase chain reaction methodologies, many molecular lesions have now been identified in the PAH gene, and their association with different PAH haplotypes and disease phenotypes can now be addressed in a rational manner. Finally, the characterization of PAH mutations has enabled the population dynamics of phenylketonuria to be examined in several different populations. PMID- 1943688 TI - Alcaptonuria and ochronotic arthritis. AB - The rare hereditary metabolic disorder alcaptonuria is characterized by the inability to metabolize homogentisic acid, an intermediary compound in the catabolism of the aromatic amino acids phenylalanine and tyrosine. The essentially complete deficiency of homogentisic acid oxidase causes a striking accumulation of homogentisic acid and a derived melanin-like pigment in the connective tissues; the latter is termed ochronosis. Urinary homogentisic acid is oxidized rapidly and becomes a brown or black pigment if alkali is added. Older alcaptonurics have intensely pigmented (ochronotic) connective tissues, primarily the cartilaginous joint surfaces, ribs, intervertebral disks, ear cartilage, etc. They also have an unusual type of arthritis affecting the large weight-bearing joints, i.e. hips, knees and spine, but not the small joints of the hands and feet, as in rheumatoid arthritis. A mechanistic explanation for ochronotic arthritis has not been worked out, but it is clear that accumulation of homogentisic acid in the connective tissues directly or indirectly leads to the arthritic changes. A detailed analysis of the events leading to alcaptonuric arthritis should be worthwhile since it is a model form of arthritis secondary to a well-defined metabolic disorder that must persist for many years before the arthritic complications appear. Possibly other, more common types of arthritis, develop secondarily to metabolic disturbances that involve chemical mediators less obvious, or less easily detected, than homogentisic acid. PMID- 1943689 TI - Molecular defects in the E1 alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex that cause maple syrup urine disease. AB - Maple syrup urine disease (MSUD) results from an inborn metabolic error caused by a deficiency of the branched-chain alpha-ketoacid dehydrogenase complex (BCKDC). cDNA clones encoding the E1 alpha subunit of BCKDC from rat and human liver have been isolated and characterized. The chromosomal location of E1 alpha on chromosome 19q13.1-13.2 has been determined using complementary methods. The etiology of MSUD has been studied by determining the enzyme activity, protein mass and mRNA level of BCKDC in fibroblasts from a human family and Polled Hereford calves, both with classic MSUD. A TACTyr to AACAsn substitution at residue 394 of the E1 alpha subunit was identified in the human patient by using enzymatic amplification of mRNA followed by DNA sequencing. Amplification of both mRNA and genomic DNA, in combination with allele-specific oligonucleotide hybridization, demonstrated that the patient was a compound heterozygote, inheriting an allele with a structural mutation from the father, and an allele from the mother containing a presumably cis-acting defect in regulation that abolished the expression of one of the E1 alpha alleles. The results revealed for the first time that a case of MSUD was caused by structural and regulatory mutations involving the E1 alpha subunit. Recent studies by others have demonstrated that the same structural mutation as is found in this patient is responsible for the high incidence of MSUD in the Philadelphia Mennonite population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943690 TI - Maple syrup urine disease: domain structure, mutations and exon skipping in the dihydrolipoyl transacylase (E2) component of the branched-chain alpha-keto acid dehydrogenase complex. AB - Maple syrup urine disease (MSUD) is an autosomal recessive disorder in the oxidative decarboxylation of the branched-chain alpha-keto acids derived from leucine, isoleucine and valine. The enzyme deficient in MSUD, the branched-chain alpha-keto acid dehydrogenase (BCKAD) complex, is a mitochondrial multienzyme complex consisting of at least six distinct subunits. MSUD is genetically heterogeneous as manifested by lesions in different subunits of the BCKAD complex among unrelated patients. To approach the biochemical basis of MSUD involving the dihydrolipoyl transacylase (E2) subunit, the domain structure of this polypeptide from human and bovine livers has been defined by limited proteolysis and cDNA cloning. The assembly of 24 E2 subunits into a cubic structure, forming the core of the mammalian BCKAD complex, was established by electron microscopy and sedimentation equilibrium analysis. Highly assembled bovine E2 devoid of prosthetic lipoic acid has been overexpressed in Escherichia coli. Studies carried out with this bacterial expression system have provided insights into the lipoylation process of E2, and the involvement of the His391 residue in the transacylation reaction. At the genetic level, the human E2 gene (DBT) has been regionally assigned to chromosome 1p31, and a related E2 pseudogene to chromosome 3q24 by in situ hybridization. Genomic cloning has shown that the human E2 gene undergoes premature transcriptional termination and alternate splicing as normal events, although its functional significance is unknown. Through the use of the polymerase chain reaction and other recombinant DNA methods, several compound heterozygous mutations at the E2 locus have been identified in classical as well as thiamine-responsive MSUD patients. These mutations would appear to be useful genetic models, which will facilitate investigations into macromolecular organization and protein-protein interactions. Moreover, an array of precise single and multiple exon deletions has been observed in the amplified mutant E2 transcripts. The results represent unexpected secondary effects that are apparently associated with the above primary mutations in the E2 gene. PMID- 1943691 TI - Non-ketotic hyperglycinemia: an aim of the second generation of studies on pathogenesis. AB - Non-ketotic hyperglycinemia is caused by a molecular lesion involved in the glycine cleavage system and shows striking features representing the impaired central nervous system. For the study on molecular genetics of non-ketotic hyperglycinemia, we have isolated several cDNA clones, each encoding human glycine decarboxylase of H-protein, two of the four component enzymes of the glycine cleavage system. Although one of eight patients with this disease resulting from a lesion of glycine decarboxylase had the glycine decarboxylase gene deleted at a 5' region, they showed no common aberration detectable by glycine decarboxylase cDNA. Using the H-protein cDNA, we have demonstrated the rearranged structures, identified by one of the undetectable 5.0 and 5.5 kb SacI fragments, in the genomes of patients in whom there was an impaired expression of H-protein or glycine decarboxylase. The aberration of the 5.5 kb SacI fragment was associated with a defect of the 5.2 kb EcoRI fragment. Multiple genomic lesions are suggested for non-ketotic hyperglycinemia, and their implications in pathogenesis are discussed. PMID- 1943692 TI - Additional mutations in argininosuccinate synthetase causing citrullinemia. AB - Deficiency of argininosuccinate synthetase causes arginine auxotrophy in lower organisms and causes citrullinemia in humans and cattle. Previously, seven missense mutations, four mutations associated with an absence of an exon in mRNA, and one splicing mutation have been identified in human neonatal citrullinemia. Reverse transcription of mRNA, amplification of cDNA and sequencing of cDNA clones were used to identify two additional missense mutations causing citrullinemia. One mutation involves substitution of leucine for serine at position 18 (S18L) and the other a substitution of cysteine for arginine at position 86 (R86C). Both of these mutations represent C----T transitions in CpG dinucleotides, and eight of nine missense mutations causing human citrullinemia involve similar transitions in CpG dinucleotides. The nucleotide coding sequence and deduced amino acid analysis are available for four mammalian species, yeast and three bacterial species. Six of nine missense mutations in humans occur in amino acid positions that are completely conserved in these organisms. Mutations causing human citrullinemia are extremely heterogeneous, and all non consanguineous individuals studied to date are compound heterozygotes. PMID- 1943693 TI - Mucoid Pseudomonas aeruginosa in cystic fibrosis: signal transduction and histone like elements in the regulation of bacterial virulence. AB - The profuse production of the exopolysaccharide alginate results in mucoidy, a critical virulence factor expressed by Pseudomonas aeruginosa during chronic respiratory tract infections in cystic fibrosis. Studies of the regulation of this pathogenic determinant have unravelled at least two levels of control, including bacterial signal transduction systems and histone-like elements. Although only in its initial phase, an understanding of the dual control of mucoidy may help to illuminate adaptive processes that depend on the combination of these regulatory factors. Integration of specific signals transduced by the two-component systems with inputs generated by the general state of bacterial nucleoids may govern the expression of certain virulence determinants and provide a framework facilitating selection of phenotypes successful under particular environmental conditions and selective pressures. PMID- 1943694 TI - TyrR protein of Escherichia coli and its role as repressor and activator. AB - The TyrR protein regulates the expression of eight transcriptional units that comprise the TyrR regulon. In all but one case, regulation is by repression, while in two cases activation of expression can occur. Notwithstanding the fact that the TyrR protein contains an ATP-binding domain and a helix-turn-helix DNA binding domain which are structurally homologous to domains of similar functions in proteins such as NifA, NtrC, DctD and XylR, it differs from them in a number of respects. It is not a part of a two-protein component system and it lacks the amino-terminal domain that is present on NtrC and DctD. It activates transcription from 'E sigma 70, promoters but not from 'E sigma 54, promoters. ATP binding seems to be essential for tyrosine-mediated repression but not for activation. In addition, the activity of the TyrR protein is modulated by the binding of one or more of the aromatic amino acids. The consensus sequence for TyrR-binding sites in DNA, referred to as TyrR boxes, is TGTAAAN6TTTACA. Tyrosine mediated repression occurs at operators containing a pair of adjacent boxes. These have unequal affinities for the TyrR protein. The box that overlaps the RNA polymerase binding site is only bound by TyrR in the presence of both ATP and tyrosine, and binding appears to involve co-operativity between two TyrR protein dimers. In contrast, activation of expression by TyrR appears to require phenylalanine but not ATP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943695 TI - Regulation of methionine synthesis in Escherichia coli. AB - The biosynthesis of methionine in Escherichia coli is under complex regulation. The repression of the biosynthetic pathway by methionine is mediated by a repressor protein (MetJ protein) and S-adenosyl-methionine which functions as a corepressor for the MetJ protein. Recently, a new regulatory locus, metR, has been identified. The MetR protein is required for both metE and metH gene expression, and functions as a transactivator of transcription of these genes. MetR is a unique prokaryotic transcription activator in that it possesses a leucine zipper motif, first described for eukaryotic DNA-binding proteins. The transcriptional activity of MetR is modulated by homocysteine, the metabolic precursor of methionine. Finally, it is known that vitamin B12 can repress expression of the metE gene. This effect is mediated by the MetH holoenzyme, which contains a cobamide prosthetic group. PMID- 1943696 TI - Regulation of capsular polysaccharide synthesis in Escherichia coli K12. AB - Synthesis of the capsular polysaccharide colanic acid in Escherichia coli K12 is regulated by a complex network of regulatory proteins. This regulation is expressed at the level of transcription of the cps (capsular polysaccharide synthesis) genes. Two positive regulators, RcsA and RcsB, are necessary for maximal capsule expression. The availability of RcsA is normally limited because the RcsA protein is rapidly degraded by the Lon ATP-dependent protease. Therefore Lon acts, indirectly, as a negative regulator of capsule synthesis. The sequence predicted for RcsB suggests that it is the effector component of a two-component system; a protein with homology to sensors, RcsC, also plays a role in capsule regulation. We propose a model for capsule synthesis in which RcsA interacts with RcsB to stimulate transcription of the cps genes. The mechanism of regulation of colanic acid synthesis in E. coli may apply to other capsules in a variety of Gram-negative bacteria. PMID- 1943697 TI - Filamentous phage assembly. AB - Filamentous phages present a genetically well-defined system for studying the ordered membrane assembly of five different phage-encoded proteins around the circular single-stranded DNA phage genome. Assembly occurs at high efficiency in vivo, catalysed by two phage-encoded membrane proteins and at least one host protein, thioredoxin. This review presents a description of the virion and its cytoplasmic precursor and summarizes the results of genetic and biochemical experiments that are beginning to elucidate the role of the three morphogenetic proteins. The recent discovery of bacterial transport proteins with homology to a phage morphogenetic protein located in the outer membrane suggests the existence of a common mechanism for moving complex macromolecules across bacterial membranes. PMID- 1943698 TI - The repair of double-strand breaks and S1 nuclease-sensitive sites can be monitored chromosome-specifically in Saccharomyces cerevisiae using pulse-field gel electrophoresis. AB - Repair under non-growth conditions of DNA double-stranded breaks (DSBs) and S1 nuclease-sensitive sites (SSSs; e.g. DNA damage which is processed by in vitro treatment with S1 nuclease to DSBs) induced by [60Co]-gamma-rays (200 Gy; anoxic conditions) was monitored in a diploid repair-competent strain of Saccharomyces cerevisiae. We used pulsed-field gel electrophoresis (PFGE), which allows the separation of chromosome-sized yeast DNA molecules, to determine the number of DSBs and SSSs in individual chromosome species of yeast. Our results indicate that SSSs which have been regarded as clusters of base damage in opposite DNA strands are repaired efficiently in a repair-proficient diploid strain of yeast. The time course of SSS repair is comparable to the one of DSB repair, indicating similarities in the molecular mechanism. Both types of repair kinetics are different for different chromosome species. PMID- 1943699 TI - Thirty-three nucleotides of 5' flanking sequence including the 'TATA' box are necessary and sufficient for efficient U2 snRNA transcription in Schizosaccharomyces pombe. AB - We have sequenced the 5' flanking region of the U2 gene and compared this with the 5' flanking sequences of other snRNA genes from Schizosaccharomyces pombe. This revealed no regions of clear homology 5' to a region surrounding the 'TATA' box at -32 to -29. Deletion analysis shows that a 5' flanking region extending to only -33 is sufficient for accurate and efficient transcription of U2 in Schizosaccharomyces pombe. PMID- 1943700 TI - Topographic analysis of the toxic Gef protein from Escherichia coli. AB - The chromosomal gef gene of Escherichia coli is a member of the gef gene family which encodes strongly toxic proteins of about 50 amino acids. We demonstrate here that the Gef protein is detectable by anti-peptide antibodies. Furthermore, we show that Gef is anchored in the cytoplasmic membrane by the N-terminal part of the protein, and that the C-terminal part is localized in the periplasm in a dimeric form with at least one disulphide bond. By mutagenesis of gef it is shown that the periplasmic portion of Gef encodes the toxic domain and that the dimerization of Gef is not essential for the toxic effect. PMID- 1943701 TI - The gef gene from Escherichia coli is regulated at the level of translation. AB - We describe post-transcriptional regulation of the chromosomal gene, gef, from Escherichia coli. The gef gene is a member of a gene family consisting of the chromosomal gef and relF genes from Escherichia coli and the hok, flmA, srnB, and pndA genes, which are situated on conjugative plasmids. All the genes encode small, toxic proteins of approximately 50 amino acids which are functionally and structurally homologous. Furthermore, the gene family shares post-transcriptional regulation of expression, albeit by different mechanisms. We demonstrate here that translation of gef is coupled to an upstream open reading frame which, in turn, is regulated by a transacting factor, probably an antisense RNA. PMID- 1943702 TI - In vitro activation of Escherichia coli prohaemolysin to the mature membrane targeted toxin requires HlyC and a low molecular-weight cytosolic polypeptide. AB - The c. 110 kDa haemolysin toxin secreted by Escherichia coli and other pathogenic Gram-negative bacteria is synthesized as the non-toxic precursor, prohaemolysin (proHlyA), which is unable to target mammalian cell membranes until activated intracellularly by an unknown mechanism dependent upon the coexpressed c. 20 kDa protein, HlyC. We have established in vitro post-translational activation of proHlyA in membrane-depleted cell extract fractions from E. coli recombinant strains containing (separately) the proHlyA and HlyC proteins. In vitro activation was calcium-independent and effective over a pH range of 6 to 9 and at temperatures from 42 degrees C to 4 degrees C. HlyC cell extract was also able to activate proHlyA which had been secreted out of cells containing the export proteins HlyB and HlyD. Fractionation of HlyC cell extracts by sucrose gradient centrifugation and molecular weight chromatography revealed activating fractions as having a molecular mass of 40 kDa, suggesting that the HlyC activator is present physiologically in a multimeric form. Cell extracts containing activation competent HlyC and proHlyA were inactive following dialysis, but activity was restored by complementation with a cell extract lacking both proteins. HlyC and proHlyA proteins which were overproduced separately from recombinant expression plasmids were inactive following purification, but activity could again be restored with a Hly-negative cell extract. These experiments demonstrated that HlyC is not sufficient for activation; an additional cellular factor is required. The cellular factor was found in enterobacteria but not other bacteria or eukaryotic cells. It was cytosolic, protease-sensitive, and behaved as a c. 10 kDa polypeptide in a number of assays including dialysis, sucrose gradient centrifugation, and gel filtration chromatography. Thus activation was possible in a defined in vitro reaction containing only purified proHlyA, HlyC, and the cellular factor. Kinetic studies in which the relative concentrations of the three components of proHlyA activation were varied suggested that neither HlyC nor the cellular factor acts as a conventional enzyme, with each participating in a finite number of activation events. PMID- 1943703 TI - Preferential cytoplasmic location of FtsZ, a protein essential for Escherichia coli septation. AB - An ftsZ thermonull mutant has been constructed in which the ftsZ gene has been deleted from the Escherichia coli chromosome while maintaining a wild-type copy of the gene in a thermosensitive plasmid. Under conditions in which the ftsZ+ allele is unable to be replicated at the same pace as the chromosome, the cells become non-viable and grow as filaments, indicating that, contrary to other reports, FtsZ performs a function essential for cell survival. Antibodies raised against FtsZ have been used to detect the cellular location of FtsZ and its contents per cell. Fractionation experiments indicate that most of the total FtsZ present in the cell stays in the cytoplasm. PMID- 1943704 TI - Both genes for EF-1 alpha in Candida albicans are translated. AB - In previous work, we showed that Candida albicans has two genes, TEF-1 and TEF-2, which encode identical polypeptides for the highly conserved, essential, protein synthesis factor EF-1 alpha (Breviario et al., 1988). This result prompted questions as to whether C. albicans preferentially uses one of the genes over the other and whether both genes are actually translated into protein. Gene-specific sequence differences in the untranslated portion of each gene made it possible to prepare gene-specific oligonucleotide hybridization probes. Results with the probes showed that the relative steady-state mRNA levels of the two genes were equivalent and that the mRNA for each gene was present in active translation complexes. PMID- 1943706 TI - Marker exchange mutagenesis of the hydN genes in Desulfovibrio fructosovorans. AB - A strain of Desulfovibrio fructosovorans deleted from the hydN [NiFe]hydrogenase structural gene was constructed. A plasmid carrying a 7 kb DNA fragment on which the hydN gene had been replaced by the npt reporter gene (kanamycin-resistant, KnR) was introduced into D. fructosovorans by electroporation. Southern analysis of one KnR clone demonstrated that the hydN gene had been eliminated by marker exchange. This mutant, which was devoid of the [NiFe]hydrogenase gene, still showed a 10% residual hydrogenase activity. Its ability to grow efficiently with H2 as sole energy source is discussed. This is the first report, in a member of the sulphate-reducing bacteria, of a successful transformation and concomitant homologous recombination leading to a fully controlled genotype. PMID- 1943705 TI - Purification and mutant analysis of Citrobacter freundii AmpR, the regulator for chromosomal AmpC beta-lactamase. AB - AmpR, the transcriptional regulator for the Citrobacter freundii ampC beta lactamase gene, was purified. The purified AmpR had DNA-binding activity, the same molecular mass (32 kDa) on sodium dodecyl sulphate/polyacrylamide gel electrophoresis as previously described, and N-terminal sequencing of the first 15 amino acids was in agreement with that predicted from the nucleotide sequence. Two mutants were isolated that abolish DNA-binding and beta-lactamase induction and which map in the amino- and carboxyl-terminal ends of AmpR, respectively. The mutation in the amino terminus (S35F) was located in a helix-turn-helix region showing high homology to other members of the LysR regulator family. Therefore this mutation may directly abolish the contact between AmpR and its operator sequence. It is suggested that the C-terminal mutation (Y264N) affects subunit interactions in AmpR. One constitutive mutant was isolated which mapped in the centre of the ampR gene. This G102E mutant leads to constitutive beta-lactamase expression in the absence of both beta-lactam inducer and ampG, a gene essential for induction in wild-type enterobacteria. Another mutant protein, D135Y, showed wild-type properties in an ampG+ and an ampG::kan background, but could, unlike wild-type AmpR, activate the ampC gene in an ampG1 mutant background. It is thought that ampG1 is a missense mutant. These two types of ampR mutants suggest that activation of ampC transcription is dependent on the conversion of AmpR into a transcriptional activator and that this activation may normally involve interactions with AmpG. PMID- 1943707 TI - Absence of acetohydroxy acid synthase III in Salmonella typhimurium is due to early termination of translation within the ilvl gene. AB - The cryptic ilvlH locus of Salmonella typhimurium has genetic information for two distinct subunits of acetohydroxy acid synthase III. We show that the ilvH encoded subunit is normally translated and the lack of activity is due to early termination of translation within the promoter-proximal ilvl gene. Analysis of the 5' region of the operon led to identification of the promoter and the amino terminal part of ilvl. Expression of this gene in a mutant producing acetohydroxy acid synthase is due to a transversion which creates a UUA (leucine) codon in the place of a UGA (stop) codon present in position 12 of the wild-type coding region. PMID- 1943708 TI - Analysis of structure and function of the B subunit of cholera toxin by the use of site-directed mutagenesis. AB - Oligonucleotide-directed mutagenesis of ctxB was used to produce mutants of cholera toxin B subunit (CT-B) altered at residues Cys-9, Gly-33, Lys-34, Arg-35, Cys-86 and Trp-88. Mutants were identified phenotypically by radial passive immune haemolysis assays and genotypically by colony hybridization with specific oligonucleotide probes. Mutant CT-B polypeptides were characterized for immunoreactivity, binding to ganglioside GM1, ability to associate with the A subunit, ability to form holotoxin, and biological activity. Amino acid substitutions that caused decreased binding of mutant CT-B to ganglioside GM1 and abolished toxicity included negatively charged or large hydrophobic residues for Gly-33 and negatively or positively charged residues for Trp-88. Substitution of lysine or arginine for Gly-33 did not affect immunoreactivity or GM1-binding activity of CT-B but abolished or reduced toxicity of the mutant holotoxins, respectively. Substitutions of Glu or Asp for Arg-35 interfered with formation of holotoxin, but none of the observed substitutions for Lys-34 or Arg-35 affected binding of CT-B to GM1. The Cys-9, Cys-86 and Trp-88 residues were important for establishing or maintaining the native conformation of CT-B or protecting the CT B polypeptide from rapid degradation in vivo. PMID- 1943709 TI - Characterization of the oriT region of the IncFV plasmid pED208. AB - DNA sequence analysis of a 2.2kb EcoRI-HindIII fragment from pED208, the derepressed form of the IncFV plasmid Folac, revealed sequences highly homologous to the oriT region, traM, and traJ genes of other IncF plasmids. The TraM protein was purified and immunoblots of fractionated cells containing pED208 or Folac showed that TraM was predominantly in the cytoplasm. Using DNA retardation assays and the DNase I footprinting technique, the TraM protein was found to bind to three large motifs in the oriT region: (I) an inverted repeat, (II) two direct repeats, and (III) the traM promoter region. These three footprint regions contained a Hinfl-like sequence (GANTC) that appeared 16 times, spaced 11-12 bp (or multiples thereof) apart, suggesting that TraM protein binds in a complex manner over this entire region. PMID- 1943710 TI - Differential decay of a polycistronic Escherichia coli transcript is initiated by RNaseE-dependent endonucleolytic processing. AB - Differential expression of the genes expressing Pap pili in Escherichia coli was suggested to involve mRNAs with different stabilities. As the result of a post transcriptional processing event, a papA gene-specific mRNA product (mRNA-A) accumulates in large excess relative to the primary mRNA-BA transcript. Our results show that the processed product, mRNA-A, is a translationally active molecule and that it is generated from the mRNA-BA precursor by an RNaseE dependent mechanism. The processing did not occur under non-permissive conditions in an E. coli rne mutant strain with a temperature-sensitive RNaseE. The endonuclease RNaseE was previously described as being chiefly involved in the processing of the 9S precursor of 5S rRNA. A comparison of nucleotide sequences of mRNA-BA and three other RNAs processed by RNAseE revealed a conserved motif around the cleavage sites. Mutations abolishing the activity of either of two other endoribonucleases, RNaseIII and RNaseP, did not affect the pap mRNA processing event. However, a conditional mutation in the ams locus, causing altered stability of bulk mRNA in E. coli, led to reduced pap mRNA processing in a manner similar to the effect caused by RNaseE deficiency. Our findings are consistent with the idea that ams is related/allelic to rne. Absence of the processing event in the RNaseE mutant (rne-3071) strain led to a four-fold stabilization of the mRNA-BA primary transcript. We conclude that the RNaseE dependent processing event is the rate-limiting step in the decay of the papB coding part of the primary transcript and in the production of the stable mRNA-A product.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943711 TI - Location of the RNA-processing enzymes RNase III, RNase E and RNase P in the Escherichia coli cell. AB - Cells overexpressing the RNA-processing enzymes RNase III, RNase E and RNase P were fractionated into membrane and cytoplasm. The RNA-processing enzymes were associated with the membrane fraction. The membrane was further separated to inner and outer membrane and the three RNA-processing enzymes were found in the inner membrane fraction. By assaying for these enzymatic activities we showed that even in a normal wild-type strain of Escherichia coli these enzymes fractionate primarily with the membrane. The RNA part of RNase P is found in the cytosolic fraction of cells overexpressing this RNA, while the overexpressed RNase P protein sediments with the membrane fraction; this suggests that the RNase P protein anchors the RNA catalytic moiety of the enzyme to a larger entity. The implications of these findings for the cellular organization of the RNA-processing enzymes in the cell are discussed. PMID- 1943713 TI - Residential treatment centers and other organized mental health care for children and youth: United States, 1988. AB - Residential treatment centers (RTCs) for emotionally disturbed children are an important component of the mental health services delivery system in the United States. The 440 RTCs operating in 1988 represented 9 percent of all mental health organizations in the U.S. in that year. They served approximately 10 percent of the patients who received inpatient and residential treatment care and approximately 2 percent of outpatient psychiatric visits in organized settings. Their 39,000 full-time equivalent (FTE) staff and $1.3 billion expenditures were, respectively, 7 percent and 6 percent of the total for all mental health organizations. Between 1986 and 1988, the number of RTCs increased slightly, while the volume of residential treatment care changed little. However, partial care and outpatient care expanded in RTCs, with the number of visits in these categories increasing by 75 percent and 42 percent, respectively. FTE staff grew by 13 percent, and expenditures increased by 33 percent between 1986 and 1988. In 1988, RTCs were located in all States except North Dakota. The largest number were found in California (48), Massachusetts (38), and New York (28). By definition, all RTCs provided residential treatment care. About one-third of them also provided partial care and one-third provided outpatient care. The highest rates of additions to residential treatment care in RTCs per 100,000 civilian population were found in Minnesota and Colorado. Reflecting the role of RTCs as providers of care to children and youth, 94 percent of residential treatment patients in RTCs were under age 18. Seventy percent of residential treatment patients were male; 28 percent, black; and 10 percent, Hispanic. Approximately 94 percent had mental illness as their principal disability. In December 1988, 43,000 staff worked in RTCs; 14 percent were employed part-time, and 3 percent were trainees. Among others, the staff included approximately 900 psychiatrists, 300 other physicians, 1,700 psychologists, 4,800 social workers, and 1,000 nurses. Nationally, expenditures by RTCs averaged $5 per capita, but the highest per capita spending was $20 in Massachusetts and $14 in Arizona. The principal sources of funds for RTCs were local governments (the source of 33 percent of total funds available to RTCs), State mental health agencies (15 percent of funds), and other State government sources (21 percent of funds). RTCs focus their care on children and youth more than do any other type of mental health organization. At year-end in 1988, 64 percent of all the patients on the rolls of all types of programs in RTCs were under age 18.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1943712 TI - Secretion of a potential virulence factor, a fungal ribonucleotoxin, during human aspergillosis infections. AB - We show by cloning and nucleotide sequence analysis that the 18kDa antigen found in the urine of patients suffering from aspergillosis is related to the fungal protein toxins restrictocin and mitogillin. These are inhibitors of translation which act by catalytic inactivation of eukaryotic ribosomes; they may be implicated in the pathogenesis of the disease. PMID- 1943714 TI - Effect of UV light on DNA chain growth and replicon initiation in xeroderma pigmentosum variant cells. AB - The effects of UV light on DNA replication were examined in wild-type and xeroderma pigmentosum (XP) variant cells using DNA fiber autoradiography. Replication segments were significantly shorter in UV-exposed XP variant cells than they were in UV-exposed wild-type human cells immediately after exposure. This is consistent with data obtained by others using alkaline sucrose gradients suggesting that there is more blockage of DNA fork progression at UV-induced lesions in XP variant cells. With time, (2.5-5.0 h) the lengths of replication segments increased in both cell lines, suggesting that some type of bypass was occurring in XP variant cells or that excision repair was removing the blocking lesions. To determine if the post-replication defect in XP variant cells involved a failure to activate alternative sites of replicon initiation, high/low specific activity labeling was performed. The results obtained indicated that XP variant cells were able to activate alternative sites of replicon initiation. Therefore the unique phenotype of the XP variant cells is probably due to some other defect. PMID- 1943715 TI - Metabolic activation and cytogenetic effects of 2-amino-1-methyl-6 phenylimidazo[4,5-b] pyridine (PhIP) in Chinese hamster ovary cells expressing murine cytochrome P450 IA2. AB - We have utilized Chinese hamster ovary cell lines which stably express a murine cytochrome P450IA2 (P(3)450) cDNA to characterize more fully the mechanisms of genotoxicity of heterocyclic amines derived from cooked meats. To verify that these cell lines were capable of converting promutagens into active metabolites, we studied the microsomal metabolism and cytogenetic effects of 2-amino-1-methyl 6-phenylimidazo-[4,5-b]pridine (PhIP). Microsomal preparations derived from excision repair-deficient Chinese hamster ovary cells expressing the mouse cytochrome P(3)450 cDNA (UV5P3) converted PhIP to the genotoxic N-hydroxy-PhIP metabolite. Cytotoxic activity in UV5P3 was observed at concentrations of PhIP as low as 1 microM. Cytotoxicity of PhIP was an order of magnitude lower in a matched repair-proficient cell line (5P3R2) expressing the P(3)450 cDNA. PhIP produced a concentration-dependent increase in sister chromatid exchange (SCE) in UV5P3. N-Hydroxy-PhIP, at concentrations as low as 0.1 microM, produced an increase in SCE in both UV5P3 and in UV5 cells which lack the P(3)450 cDNA. Incubation of PhIP with UV5P3 cells increased the frequency of micronuclei (MN) in cytokinesis-blocked cells. Chromatid gaps, but not aberrations also were induced by treatment with PhIP. N-Hydroxy-PhIP produced increases in MN and chromatid gaps in both UV5 and UV5P3 cell lines; chromosomal aberrations were induced in UV5P3 cells. These results suggested that UV5P3 cells metabolize sufficient quantities of PhIP to produce cytogenetic damage and further indicated that N-hydroxylation of PhIP was requisite for mammalian genotoxicity. PMID- 1943716 TI - Genotoxicity of p-nitrocinnamaldehyde and related alpha, beta-unsaturated carbonyl compounds in two bacterial assays. AB - Seventeen cinnamaldehydes, cinnamic acids, 2-furylacroleins and related compounds were tested in the Salmonella preincubation reversion assay and in the SOS chromotest. Of eight compounds containing nitrogroups, seven were clearly mutagenic in the presence of S9 mix and six in its absence; whereas none of the parent compounds not containing a nitrogroup and none of the congeners containing chlorine, methoxy or amino groups were mutagenic. Metabolic epoxidation was excluded in additional experiments using SKF525, an inhibitor of mono-oxygenases, and trichloropropene oxide, an inhibitor of epoxide hydrolases. Less or no mutagenicity was found in the nitroreductase deficient strains Salmonella typhimurium TA100NR or TA98NR and in the O-acetyltransferase deficient strains TA100/1,8-DNP6 or TA98/1,8-DNP6 except with 5-nitro-2-furylacrolein which exhibited decreased mutagenicity in TA100NR when compared with TA100 but the highest mutagenicity in TA100/1,8-DNP6. Less or no genotoxic activity was found in the SOS chromotest when using the nitroreductase deficient Escherichia coli strain PQ253 whereas all seven compounds tested were positive in strain PQ37. The results demonstrate the importance of the nitro group and that the compounds are activated either by bacterial nitroreductase or by the nitroreductase in the S9 mix. A chemical activation of the acrolein moiety by the negative inductive effect of the nitro group is unlikely. The genotoxicity of the cinnamyl compounds is dependent on the position of the nitro group in the phenyl ring. The genotoxicities of the p-nitro compounds were about two orders of magnitude higher than those of the ortho and meta congeners. The comparison between the Ames test and the SOS chromotest showed good agreement. PMID- 1943717 TI - Mutagenic activity of aziridinyl steroids and their mechanism of action in biological systems. AB - The aziridinyl derivatives of steroids, structurally related to cholesterol, were tested for their mutagenic activity in the Ames tester strains. The test compounds were mutagenic without metabolic activation, although metabolic activation markedly enhanced their activity. A significant decrease in the survival of SOS defective mutants, recA and lexA of Escherichia coli was observed as compared with their wild-type counterpart in the presence of the steroids. The role of SOS repair genes gains further support from the lambda prophage induction in the lysogen and beta-galactosidase induction in the Mud strains as well as mutagenesis with Ames tester strains. Structural features which appear essential for mutagenic activity in these strains are (i) a reactive N-aminophthalamide group at the (5,6-b) position and (ii) an acetoxy/chlorine group at the third position of the steroidal nucleus. The individual moieties/groups were not mutagenic per se. These steroids appear to generate H2O2 as well as superoxide and hydroxyl radicals in the model biological system. PMID- 1943718 TI - Investigations into the induction of aneuploidy and polyploidy in mammalian cells by the anti-tussive agent noscapine hydrochloride. AB - Noscapine, a non-narcotic, centrally-acting anti-tussive drug induces polyploidy in Chinese hamster CHL cells; further studies were carried out to investigate whether similar effects could be induced in other rodent cells (Chinese hamster V79) and in human lymphocytes. In both cases, large increases in the frequency of polyploid cells were induced at test concentrations ranging from 15 to 120 micrograms/ml after 24 and 48 h continuous treatment in the absence of S9 mix. In addition, spindle damage was observed in V79 cells and human skin fibroblasts after 24 h treatment with test concentrations of 30 and 60 micrograms/ml. Furthermore, after treatment of human skin fibroblasts there was a marked increase in the proportion of cells containing chromosomes which had become dislocated from the spindle. Treatment of the mouse/human hybrid cell line R3-5 induced a significant increase in the number of 6-thioguanine resistant colonies and it was confirmed cytogenetically that these colonies had arisen due to loss of human chromosome 2. From these experiments it can be concluded that noscapine induces polyploidy in both rodent and human somatic cells, and that this could arise through a direct effect upon spindle structure and/or function. The aneugenic properties of noscapine are less certain and further work is required in this area. Exposure to the drug through its therapeutic use (15mg up to four times daily) could exceed, at least locally within the gastrointestinal (GI) tract, the concentration range shown to be active in these in vitro studies. An immediate topical hazard might exist within the buccal cavity and GI tract, but further confirmation of these in vitro results are required using suitable in vivo systems before definite conclusions can be made regarding any potential hazard associated with the administration of this drug. PMID- 1943719 TI - Study on the mutagenic activity of 13 bioflavonoids with the Salmonella Ara test. AB - The mutagenicity of 13 flavonoids has been investigated with the L-arabinose forward mutation assay of Salmonella typhimurium. Each flavonoid was tested by both plate incorporation and preincubation mutagenesis protocols in the presence or the absence of mammalian metabolic activation (S9 mixture). All flavonoids gave a dose-response relationship and induced a number of AraR mutants considered statistically significant. Their minimum mutagenic doses (MMD) differed markedly in the Ara test, covering a 400-fold range: from 4 nmol for quercetin to 1626 nmol for taxifolin. Flavonols were the strongest mutagens, with mutagenic potencies (MMD-1) representing from 27 to approximately 2% that of quercetin. Comparatively, the mutagenicities of other flavonoids represented only less than or equal to 1%. The data reported in this paper for the Ara forward mutation test suggest structural requirements for mutagenicity of bioflavonoids like those previously reported for the His reverse mutation assay: (i) flavonols with a free hydroxyl at position 3 are the strongest mutagenic flavonoids, (ii) saturation of the 2,3 double bond diminishes the mutagenic potency, and (iii) free hydroxyl groups at positions 3' and 4' influence the non-requirement for metabolic activation. The mutagenic properties of quercetin and rutin in the Ara test support the idea that these flavonols are not the major putative mutagens in complex mixtures such as wine. PMID- 1943720 TI - Analysis of the aneuploidy inducing capacity of 2-chlorobenzylidene malonitrile (CS) and metabolites in V79 Chinese hamster cells. AB - The aneuploidy inducing capacity of 2-chlorobenzylidene malonitrile (CS), a chemical used as a riot control agent, and its hydrolysis products o chlorobenzaldehyde and malonitrile was studied at various exposure conditions in V79 Chinese hamster cells. Chromosomes were counted in metaphase preparations with preserved cytoplasm. A significant increase in the number of aneuploid cells was found after CS and o-chlorobenzaldehyde exposure but not after malonitrile exposure. o-chlorobenzaldehyde, which also introduced high levels of polyploid cells, seems to be an important metabolite for the aneuploidogenic effectiveness of CS. PMID- 1943721 TI - Origin of aneuploidy in relation to disturbances of cell-cycle progression. II: Cytogenetic analysis of various parameters in mouse bone marrow cells after colchicine or hydroquinone treatment. AB - The relationship between in vivo aneuploidy and cell-cycle perturbation induced by potential aneugens was investigated in mouse bone marrow cells. This work was performed within the framework of a research programme coordinated by the European Community to study the ability of 10 selected chemicals to induce aneuploidy in different systems. In this context, the effects of colchicine (COL) and hydroquinone (HQ) on cell-cycle progression, aneuploidy, polyploidy, micronucleus and sister chromatid exchange induction in mouse bone marrow cells after bromodeoxyuridine incorporation are reported. Hyperploidy and polyploidy were scored in metaphases of cells that had undergone only one division after treatment. Both chemicals induced cell-cycle lengthening, hyperploidy and micronuclei. The kinetics of hyperploidy induction by the two compounds differed in that COL was positive at 24 h, whereas HQ was positive 18 h after treatment. Only colchicine was positive for polyploidy induction and neither chemical induced sister chromatid exchange. These results are compared with similar data obtained after vinblastine (VBL) treatment. The results suggest that VBL and COL induce chromosome malsegregation via a mechanism associated with perturbations in the cell-cycle, whereas HQ induces aneuploidy independently of cell-cycle lengthening, possibly altering a chromosomal component of chromosome segregation rather than a spindle component. PMID- 1943722 TI - Effect of antioxidants on hyperoxia-induced chromosomal breakage in Chinese hamster ovary cells: protection by carnosine. AB - We have studied the effect of various compounds, known as antioxidants, on the level of hyperoxia (80-90% O2)-induced chromosomal aberrations in Chinese hamster ovary cells: ascorbic acid, alpha-tocopherol, carnosine, imidazole-4-acetic acid, glutathione monoethylester, N-acetylcysteine and ethoxyquin. Carnosine (beta alanyl-histidine) appeared to be the only compound that reduced chromosomal breakage. The effect was also present in cultures post-treated with caffeine (at 2.5 mM, 3 h before harvest), indicating that the apparent protection was not due to selective arrest of chromosomally damaged cells in the G2 phase of the cell cycle. Imidazole-4-acetic acid, a compound structurally very similar to carnosine, had no detectable effect. Ascorbic acid, N-acetylcysteine, glutathione monoethylester and ethoxyquin were found to have a pro-oxidant effect, i.e. they apparently potentiated the clastogenic effect of hyperoxia. Carnosine is the first compound shown to protect against the clastogenicity of normobaric hyperoxia and may thus be a useful tool in elucidating the underlying mechanism. PMID- 1943723 TI - Genotoxic effect of the antitumour agent homo-aza-steroidal ester of p-bis-(2 chloroethyl)aminophenoxy acetic acid (NSC 294859) tested in the Drosophila wing somatic mutation and recombination test. AB - The genotoxic activity of the new antineoplastic alkylating agent 3 beta-hydroxy 13 alpha-amino-13,17-seco-5 alpha-androstan-17-oic-13,17- lactam-p-bis-(2 chloroethyl) aminophenoxyacetate (NSC 294859) was studied in the somatic mutation and recombination test (SMART) in Drosophila melanogaster. The drug was administered to larvae which were transheterozygous for two recessive wing cell markers mwh and flr3. Several concentrations were tested and two of them showed a clear induction of mosaic spots, expressing the mutant phenotypes. Multiple wing hair (mwh) spots were the main type observed but twin spots and flares (flr3) spots were also detected. We conclude that the compound induces both mutations and somatic recombination in the SMART test. PMID- 1943724 TI - Roles of hypoalbuminemia and lipoprotein lipase on hyperlipoproteinemia in continuous ambulatory peritoneal dialysis. AB - To assess the mechanism of serum lipoprotein abnormalities in continuous ambulatory peritoneal dialysis (CAPD), we measured serum lipids, apolipoproteins, and postheparin lipases in 46 patients with end-stage renal disease (ESRD) treated on CAPD, 26 patients on hemodialysis (HD), and 29 healthy subjects. HD patients had higher serum triglyceride levels than the healthy controls, showing type IV and type III phenotypes. They had significantly lower activities of hepatic triglyceride lipase (HTGL) in postheparin plasma compared with controls, and postheparin lipoprotein lipase (LPL) was also decreased by 15%, although the latter change was not statistically significant. CAPD patients had elevated levels in triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein (apo) B, showing type IV, III, and II (IIb and IIa) phenotypes. The mean LPL and HTGL activities in CAPD patients were not different from those of HD patients. CAPD patients with hyperlipoproteinemia had significantly higher serum albumin levels than those with normolipidemia. There was a significant positive correlation between albumin and apo B levels in CAPD patients. In hyperlipidemic CAPD patients, there was no difference in serum albumin concentrations or HTGL activities among lipoprotein phenotypes, whereas LPL activities were significantly higher in the patients with type II than those with type IV hyperlipoproteinemia. These results suggest that there was some linkage between alterations in serum albumin and lipoproteins, and that LPL was related to phenotypic variation of hyperlipoproteinemia in CAPD. PMID- 1943725 TI - Masking of diabetic phenotype on a low-energy diet despite persistence of impaired insulin response. AB - Type 2 diabetes has been postulated to be a "thrifty genotype" that aids fuel conservation; to investigate this hypothesis, type 2 diabetic and nondiabetic subjects, normal weight and obese, were studied after both 6 days on a 700 calorie diet and 6 days on a 2,800-calorie diet. On 2,800 calories per day, the median basal plasma glucose was raised in diabetics compared with nondiabetic subjects (median, 5.5 and 4.5 mmol/L, respectively; P = .003), but on the low energy diet there was no difference (4.1 and 3.7 mmol/L, respectively; P greater than .05). Basal plasma insulin levels were similar in the diabetic and nondiabetic subjects and were twofold to threefold higher on the high- than low energy diet in both diabetic (median, 7.8 and 3.1 mU/L on high- and low-energy diets, respectively; P = .007) and nondiabetic subjects (6.8 and 2.6 mU/L, respectively; P = .005). Similarly, the postprandial insulin concentrations increased to the same degree on the high- compared with the low-energy diet in diabetic (median postprandial increment, 14.9 and 3.4 mU/L; P = .005) and nondiabetic patients (9.5 and 3.0 mU/L; P = .005) and the beta cells in type 2 diabetes appeared to modulate normally to different calorie intakes. On both diets, the diabetic subjects had an impaired first-phase insulin response to an intravenous glucose load compared with nondiabetic subjects (high-energy diet median first-phase increment, 4.3 and 21.2 mU/L in diabetic and nondiabetic subjects, P = .0007; low-energy diet, 4.0 and 20.4 mU/L, respectively, P = .003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943726 TI - Prevention of glomerular basement membrane thickening by aminoguanidine in experimental diabetes mellitus. AB - The etiology of diabetic glomerulopathy appears to be related, at least in part, to the degree of hyperglycemia, the resultant nonenzymatic glycosylation of proteins, and the eventual formation of advanced glycosylation end products in long-lived structural proteins. To investigate the relationship between the glomerular basement membrane (GBM) changes of diabetic nephropathy and the formation of advanced glycosylation end products, we studied control rats, diabetic rats, and control and diabetic rats who received aminoguanidine, a compound that pharmacologically inhibits formation of advanced glycosylation end products. After 9 months, rat weight was smaller and kidney weight larger in both diabetic groups compared with both control groups. GBM width was increased in the diabetic group compared with the control group. Aminoguanidine administration to diabetic rats ameliorated this increase in GBM. Thus, aminoguanidine administration from the onset of experimental diabetes prevented the widening of the GBM that is typical of diabetes. PMID- 1943727 TI - The effect of CP 68,722, a thiozolidinedione derivative, on insulin sensitivity in lean and obese Zucker rats. AB - The effect of a new drug (CP 68,722, Pfizer) on parameters of insulin sensitivity in an established insulin-resistant animal model was examined. Rates of hepatic glucose production (HGP) and peripheral glucose uptake in obese Zucker (fa/fa) rats treated with a 10-day course of the medication using a two-step (2 and 10 mU/kg/min) euglycemic hyperinsulinemic clamp technique were measured. In addition, changes in substrate concentrations after drug treatment were examined. Basal HGP rates were similar in the lean versus the obese animals (37 +/- 3 v 39 +/- 3 mumol/kg/min); however, the obese animals had impaired insulin-induced suppression of HGP at both 2 mU/kg/min (36 +/- 3 v 23 +/- 4 mumol/kg/min) and 10 mU/kg/min (18 +/- 5 v 2 +/- 1 mumol/kg/min). Insulin stimulation of glucose disposal was also defective in the obese animals (37 +/- 2 v 88 +/- 7 mumol/kg/min at 2 mU/kg/min and 98 +/- 9 v 219 +/- 18 mumol/kg/min at 10 mU/kg/min). In addition, obese animals had elevated free fatty acid (FFA) and ketone levels, both of which were resistant to insulin-induced suppression. After drug treatment, few alterations in glucose or lipid metabolism were found in the lean animals. In the obese animals, insulin suppression of HGP was normalized during the higher insulin infusion rate (0 v 18 +/- 5 mumol/kg/min at 10 mU/kg/min), and peripheral glucose disposal was enhanced at both steps of the insulin clamp (54 +/- 4 v 37 +/- 2 mumol/kg/min at 2 mU/kg/min and 134 +/- 12 v 98 +/- 9 mumol/kg/min at 10 mU/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943728 TI - Phytohemagglutinin-stimulated lymphocytes from patients with systemic lupus erythematosus demonstrate DNA damage. AB - DNA samples from control and lupus lymphocytes were studied for DNA integrity and single-strand breaks by agarose gel electrophoresis following digestion with the enzyme S1 nuclease. S1 nuclease digests single-strand gaps in double-stranded DNA. Gel patterns of phytohemagglutinin (PHA)-stimulated control and lupus lymphocyte DNAs were identical in the absence of S1 nuclease incubation. DNA isolated from PHA-stimulated control lymphocytes was relatively resistant to S1 nuclease digestion in 14 of 16 samples. However, 15 of 16 DNA samples from PHA stimulated lupus lymphocytes demonstrated dramatically greater S1 nuclease digestion than paired control DNAs from lymphocytes analyzed at the same time under the same conditions. Increased S1 sensitivity suggests that more single strand DNA breaks were found in PHA-stimulated lupus lymphocytes and/or the lupus DNA was more damaged than control DNA. We suggest that structural changes found in DNA from stimulated T lymphocytes of lupus patients are consistent with an endogenous antigen-mediated disorder. PMID- 1943729 TI - Effects of cocaine, exercise, and resting conditions on plasma corticosterone and catecholamine concentrations in the rat. AB - Cocaine and exercise are both known as stressors, but little is known about the combined effects of these two treatments. In this study, rats under the influence of cocaine (12.5 mg/kg, intraperitoneally [IP]) or saline were exposed to a variety of resting conditions, as well as exercise (running, 26 m/min, 10% grade, for 30 minutes), to evaluate the amount of stress imposed by these conditions as determined by the changes in the plasma concentrations of corticosterone (C) and catecholamines (norepinephrine [NE], epinephrine [E], dopamine [DA]). After injection of saline, resting near the operating treadmill for 30 minutes caused the concentration of C to increase from 0.07 +/- 0.03 to 0.30 +/- 0.05 microgram/mL (P less than .05), compared to the increase to only 0.15 +/- 0.04 micrograms/mL after resting in a cage. This increase due to proximity to the treadmill subsided after 50 minutes. After cocaine, the 30-minute resting values were 0.70 +/- 0.15 (treadmill) and 0.55 +/- 0.13 (cage) (P less than .05), and did not subside after 50 minutes. Cocaine also increased levels of E, NE, and DA above those in saline under all rest conditions. With exercise, the value for C in saline increased to 0.61 +/- 0.18, but, in cocaine, the value went to 0.93 +/- 0.05 (P less than .05). The concentrations of E (946 +/- 74 v 603 +/- 101 pg/mL, cocaine v saline) and NE (1,027 +/- 102 v 440 +/- 153, cocaine v saline) during exercise also were exaggerated by cocaine treatment (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943730 TI - Clinical utility of red blood cell carbonic anhydrase I and zinc concentrations in patients with thyroid diseases. AB - We have recently reported that, in patients with hyperthyroidism, the red blood cell (RBC) carbonic anhydrase I (CAI) and zinc (Zn) concentrations both reflect the patient's integrated thyroid hormone level over the preceding few months. In this study, we evaluated the clinical usefulness of determining the RBC CAI and Zn concentrations in patients with various types of thyroid disease. Six patients with painless thyroiditis (PT) had normal RBC CAI concentrations and the two patients tested had normal RBC Zn levels. In four patients with syndromes of inappropriate thyrotropin (TSH) secretion (SITSH) two euthyroid patients had normal RBC CAI and two hyperthyroid patients had subnormal RBC CAI and Zn. In a patient with Graves' disease whose plasma thyroxine (T4) and triiodothyronine (T3) concentrations changed remarkably because of poor compliance with the regimen, the change in plasma thyroid hormone levels preceded the change in the RBC CAI and Zn concentrations by 2 to 3 months. These observations suggest that the measurement of RBC CAI and Zn concentrations may be useful clinically as follows: (1) in differentiating hyperthyroid Graves' disease from transient hyperthyroidism due to destructive thyroiditis; and (2) in obtaining an accurate estimate of the extent of elevated thyroid hormone levels in hyperthyroid patients over time. PMID- 1943731 TI - A dose-response relationship between sex hormone-induced change in hepatic triglyceride lipase and high-density lipoprotein cholesterol in postmenopausal women. AB - In previous studies, we have demonstrated a temporal relationship between the postheparin hepatic triglyceride lipase (HTGL) response to sex steroids and the high-density lipoprotein (HDL) cholesterol response. To determine if this relationship is dose-dependent, we compared the effect of three graduated doses of orally administered estradiol and norgestrel in two groups of six postmenopausal women. With estradiol administration, postheparin HTGL activity decreased from 91 +/- 46 to 50 +/- 29 nmol/min/mL, baseline to high dose (P less than .05); HDL cholesterol increased from 54 +/- 6 to 64 +/- 10 mg/dL (P less than .05); HDL2 cholesterol increased from 16 +/- 4 to 23 +/- 7 mg/dL (P less than .05); and HDL3 cholesterol concentration did not change. With norgestrel administration, HTGL activity increased from 79 +/- 19 to 109 +/- 24 nmol/min/mL (P less than .05); HDL cholesterol decreased from 64 +/- 17 to 43 +/- 7 mg/dL (P less than .05); HDL2 cholesterol decreased from 21 +/- 17 to 6 +/- 5 mg/dL (P less than .05); and HDL3 cholesterol concentration decreased from 43 +/- 8 to 38 +/- 8 mg/dL (P less than .05). The HTGL activity response was inversely correlated with estrogen dose (rs = -.733, P = .0001) and directly correlated with progestin dose (rs = .895, P = .0001). The HDL cholesterol response was directly correlated with estrogen dose (HDL: rs = .741, P = .001; HDL2: rs = .586, P = 0.003) and inversely correlated with progestin dose (HDL: rs = -.933, P = .0001; HDL2: rs = -.866, P = .0001; HDL3: rs = -.576, P = .003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943732 TI - The effects of epinephrine on ketogenesis in the dog after a prolonged fast. AB - The effects of a selective increase in epinephrine on ketogenesis and lipolysis were determined in the conscious dog following a prolonged fast (7 days). Plasma insulin and glucagon were fixed at basal levels by infusion of somatostatin (0.8 micrograms/kg/min) and basal intraportal replacement amounts of insulin (210 +/- 20 microU/kg/min) and glucagon (0.65 ng/kg/min). Following a 40-minute control period, saline or epinephrine (0.04 microgram/kg/min) was infused for 3 hours. Plasma insulin, glucagon, and norepinephrine levels did not change during saline (6 +/- 1 microU/mL, 83 +/- 17 pg/mL, and 137 +/- 38 pg/mL, respectively) or epinephrine (10 +/- 1 microU/mL, 73 +/- 18 pg/ml, 98 +/- 13 pg/mL, respectively) infusion. Plasma epinephrine levels increased from 80 +/- 26 to 440 +/- 47 pg/mL in response to infusion of the catecholamine, but remained unchanged during saline infusion. Glycerol levels (93 +/- 10 mumol/L) remained unchanged during saline infusion, but increased in response to epinephrine (108 +/- 9 to 170 +/- 18 mumol/L by 30 minutes). The glycerol level had returned to baseline and to the value apparent in saline controls by 60 minutes. The nonesterified fatty acid (NEFA) level declined slowly during the 3-hour saline infusion, but was elevated in response to epinephrine infusion (1.27 +/- 0.16 to 1.97 +/- 0.25 mmol/L at 30 minutes). After the initial epinephrine-induced increase, the NEFA level declined so that by 3 hours it was not significantly different from the basal or saline values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1943733 TI - Cholesterol-lowering action of psyllium mucilloid in the hamster: sites and possible mechanisms of action. AB - These studies were undertaken to examine and compare the metabolic effects of psyllium mucilloid and two other nonabsorbable polymers (cholestyramine and surfomer) on sterol metabolism in the hamster. These three agents all significantly lowered the plasma total cholesterol concentration and the level of cholesterol carried in low-density lipoproteins (LDL). Rates of cholesterol synthesis were markedly increased in the livers of the psyllium-fed animals, but not in other tissues. In contrast, cholestyramine and surfomer feeding increased both hepatic and intestinal sterol synthesis. When cholesterol and saturated triacylglycerols were added to the diet, psyllium feeding essentially completely blocked the increase in the plasma cholesterol concentration and hepatic cholesterol content and the suppression of cholesterol synthesis. The pool of bile acid in the small intestine was increased from the control value (17.9 mumol/animal) by both psyllium (23.0 mumol) and cholestyramine (21.9 mumol) feeding. However, this pool was readily absorbed and secreted into the bile in the psyllium-fed animals (27.9 mumol/4 h), but not in the cholestyramine-treated hamsters (13.0 mumol/4 h). This was consistent with the further observation that there was no binding of bile acid by psyllium under in vitro conditions. Thus, these findings indicate that all three polymers lower plasma cholesterol concentrations by inducing a net negative cholesterol balance across the liver. With psyllium, this effect is presumably articulated through a reduction in cholesterol absorption, as well as an increase in the rate of degradation of cholesterol to bile acids. PMID- 1943734 TI - Aldose reductase activity and myo-inositol levels in sciatic nerve and dorsal root ganglia of the diabetic mutant mouse [C57/BL/Ks (db/db)]. AB - Glucose, polyol (sorbitol, fructose), and myo-inositol levels were estimated in peripheral nerve tissue of the diabetic mutant mouse [C57/BL/Ks (db/db)]. At 26 and 40 weeks of age, there was significant accumulation of glucose, sorbitol, and fructose. Tissue myo-inositol levels were lower than those in age-matched control animals at 40 weeks, but not at 26 weeks. Polyol changes in mouse nerve were less marked than those in rat nerve. In dorsal root ganglia, there was also an increase in glucose, sorbitol, and fructose, with a decrease in myo-inositol concentration. These findings show that there is increased aldose reductase activity in peripheral nerve tissue of the diabetic mutant mouse. PMID- 1943735 TI - Hyperinsulinemia and glucose tolerance in obese rats with lesions of the ventromedial hypothalamus: dependence on food intake and route of administration. AB - This study was performed to investigate the consequences of developing obesity on glucose homeostasis in animals showing hyperphagia plus vagal hyperinsulinemia and rats that were normophagic and hyperinsulinemic. Male rats were lesioned in the ventromedial hypothalamus (VMH) and kept either under ad libitum or absolute (oral or intragastrical) pair-feeding conditions for 4 weeks. Hyperphagic rats, as well as normophagic VMH rats, became obese, but only ad lib-fed obese rats displayed glucose intolerance to intravenous (IV) glucose infusions. Orally pair fed VMH rats also showed normal oral and intragastric glucose tolerance, but in intragastrically fed VMH animals and controls, oral and intragastric glucose tolerance was decreased. These results indicate that (1) obesity as a consequence of VMH lesions is not dependent on hyperphagia, confirming earlier reports, and also independent of the ingestion of bulk meals. (2) beta-cell release of insulin to IV glucose infusion is not sufficient when hyperphagia and vagally mediated hyperinsulinemia coincide, and is therefore dependent on several factors; and (3) oral glucose intolerance develops when preabsorptive reflexes are blunted, irrespective of whether the animals were hyperinsulinemic or not. PMID- 1943736 TI - Reduced hypothalamic neurotensin concentrations in the genetically obese diabetic (ob/ob) mouse: possible relationship to obesity. AB - Hypothalamic tissue levels of nine regulatory peptides (bombesin, calcitonin gene related peptide [CGRP], galanin, neuromedin B, neuropeptide Y [NPY], neurotensin, somatostatin, substance P, and vasoactive intestinal peptide [VIP]) were compared in Aston obese diabetic (ob/ob) and lean (+/?) mice aged 4, 16, and 28 weeks. Neurotensin concentrations were significantly lower in ob/ob mice than in lean mice, with a 20% reduction (P = .03) in the whole hypothalamus at 4 weeks of age, a 24% reduction (P = .009) in the lateral hypothalamus at 16 weeks, and a 50% reduction (P = .0007) in the central hypothalamus at 28 weeks of age. Apart from a 42% increase in vasoactive intestinal peptide concentrations in the central hypothalamus of ob/ob mice at 28 weeks (P = .02), levels of the other eight peptides examined did not differ significantly between obese and lean groups. Neurotensin is known to cause anorexia and increased energy expenditure when injected into the central hypothalamus. Reduced hypothalamic neurotensin concentrations may reflect reduced neurotensinergic activity, which might contribute to hyperphagia and decreased energy expenditure, two major defects that contribute to obesity and diabetes in the ob/ob syndrome. PMID- 1943737 TI - Effect of hypoxia on plasma immunoreactive endothelin-1 concentration in anesthetized rats. AB - The present study was designed to examine the possible influence of hypoxia on plasma immunoreactive (ir) endothelin-1 concentrations in anesthetized rats. Plasma ir-endothelin-1 concentration, blood pressure, heart rate, and arterial gas levels were measured 1 and 2 hours after exposure to normoxic (20% O2), mildly hypoxic (16% O2), and severely hypoxic (12% O2) gas. Mean blood pressure and heart rate were significantly decreased and the plasma ir-endothelin-1 concentration was significantly increased in severely hypoxic rats after both 1 and 2 hours. In mildly hypoxic rats, the plasma ir-endothelin-1 concentration was also increased, but this value was not statistically significant. The plasma ir endothelin-1 concentration was inversely correlated with arterial blood PO2 in the three study groups (normoxic, mildly hypoxic, and severely hypoxic rats) after 1 hour (n = 18, r = -.74, P less than .01), and after 2 hours (n = 18, r = .71, P less than .01). Our results indicate that severe hypoxia increased the plasma ir-endothelin-1 level in anesthetized rats. The observed increase in plasma ir-endothelin-1 level may represent a compensatory mechanism against the blood pressure reduction associated with severe hypoxia. PMID- 1943738 TI - Patients with combined hypercholesterolemia-hypertriglyceridemia show an increased monocyte-endothelial cell adhesion in vitro: triglyceride level as a major determinant. AB - Hypercholesterolemia (HC) is one of the primary risk factors for atherosclerosis. Patients with familial hypercholesterolemia (FH) or combined hypercholesterolemia hypertriglycerinemia (CHH) are at risk to develop premature atherosclerosis. Animal models have revealed that diet-induced HC in vivo leads to an increased adhesion of monocytes to the endothelium of the vessel wall. Changes in the monocytes, endothelial cells, or serum components may lead to the increased monocyte adhesion that results in atherosclerotic plaque formation. In the present study, we investigated the binding of the monocyte in an in vitro system. Incubation of freshly isolated monocytes from CHH patients with cultured human umbilical vein endothelial cells (HUVEC) gave a significant 60% increase in monocyte adhesion when compared with monocytes from healthy subjects. No such increase was observed using monocytes from nontreated FH patients. These data suggest that CHH results in in vivo alterations of the monocytes that lead to an increased in vitro adhesion to HUVEC, and that an increased level of plasma triglycerides is the major determinant, since HC alone does not induce this alteration. PMID- 1943739 TI - Independent regulation of chylomicron lipolysis and particle removal rates: effects of insulin and thyroid hormones on the metabolism of artificial chylomicrons. AB - The processes of chylomicron lipolysis and removal from plasma were investigated by the intra-arterial infusion of doubly labeled artificial chylomicrons in rats. The rate of lipolysis was measured as a delipidation index (DI), which is the glyceryl-tri-9,10(N)-3H oleate (3H-TO) fraction removed from the particle as fatty acids, whereas the cholesteryl(1-14C) oleate (14C-CO) plasma disappearance rate measures the splanchnic organ particle uptake. In the alloxan-diabetic rats, despite a normal DI, the 14C-CO plasma residence time (RT) was longer than in control animals and remained longer after stimulation of the lipoprotein lipase by heparin. DI and 14C-CO removal rate were not significantly altered by insulin administration to glucose-supplemented control rats. Lipolysis was remarkable in propylthiouracil (PTU)-induced hypothyroidism, and yet the 14C-CO removal rate was retarded. In hypothyroidism, heparin enhanced the 14C-CO removal more than in the control group; however, after heparin, the 14C-CO RT still remained higher in the hypothyroid animals as compared with the control group. Hyperthyroidism lowered the DI; nevertheless, the 14C-CO disappearance rate was faster than in controls. In summary, lack or excess of thyroid hormone influences both the chylomicron lipolysis and removal systems, whereas lack of insulin impairs mostly the particle removal from plasma, and excess of insulin has no effect on the chylomicron metabolism. PMID- 1943740 TI - Effect of acute intravenous alcohol on plasma lipoproteins in man. AB - The effect of acute administration of ethanol was determined on plasma lipoproteins and post-heparin lipolytic activities in six normal subjects. Ethanol was administered intravenously (IV) in a dose of 0.6 g/kg body weight over 1 hour and blood samples were obtained for 4 hours thereafter. In four subjects, the determinations were repeated after the infusion of an isovolumetric amount of saline. Ethanol resulted in a rapid increase in plasma triglycerides, which persisted throughout the study. Ethanol did not result in changes in high density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, or apolipoprotein administration of heparin. The increase in triglycerides without changes in HDL-cholesterol after acute ethanol administration may contribute to an increased severity of cardiovascular disease in binge drinkers. PMID- 1943741 TI - Insulin-like growth factor-I in non-insulin-dependent diabetic monkeys: basal plasma concentrations and metabolic effects of exogenously administered biosynthetic hormone. AB - Plasma insulin-like growth factor-I (IGF-I) concentrations and the effects of exogenous IGF-I administration were determined in 26 rhesus monkeys; each animal was well characterized regarding its degree of obesity, plasma glucose and insulin levels, and glucose tolerance (KG). Five separate groups were identified: lean normal, obese normoinsulinemic and normoglycemic, obese hyperinsulinemic with normal glucose tolerance, impaired glucose tolerant, and spontaneously diabetic (type II, non-insulin-dependent diabetes mellitus [NIDDM]). Basal plasma IGF-I levels in all monkeys ranged from 249 to 1,093 ng/mL and were strongly associated with age (r = -.66; P less than .001) and KG (r = .59; P less than .001), but not with body weight, body fat, or fasting plasma glucose or insulin levels. In addition, the acute insulin-like effects of exogenously administered IGF-I on glucose disappearance were studied in vivo in a dose-response comparison to insulin (subcutaneous administration of IGF-I at doses of 50, 100, or 200 micrograms/kg v insulin at 0.3 U/kg). Five hyperinsulinemic normoglycemic monkeys (fasting plasma glucose, 67 +/- 2 mg/dL; insulin, 163 +/- 42 microU/mL) and overt type II diabetic monkeys (fasting plasma glucose, 201 +/- 13 mg/dL; insulin, 38 +/- 6 microU/mL) each underwent a series of three to five experiments to determine the time course and degree of hypoglycemia induced by IGF-I as compared with insulin or with control (saline) injection.(ABSTRACT TRUNCATED AT 250 WORDS)